Ovarian Serous Cystadenocarcinoma: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
PLK2 and PLK4 events	187
FOXM1 transcription factor network	142
TCGA08_p53	104
HIF-1-alpha transcription factor network	96
Ephrin B reverse signaling	96
Wnt signaling	96
Osteopontin-mediated events	91
LPA receptor mediated events	91
PDGFR-alpha signaling pathway	88
Endothelins	88

Pathway.Name	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
PLK2 and PLK4 events	187	561	3	-0.011	0.036	1000	-1000	-0.017	-1000
FOXM1 transcription factor network	142	7291	51	-0.52	0.038	1000	-1000	-0.016	-1000
TCGA08_p53	104	730	7	-0.063	0.038	1000	-1000	-0.009	-1000
HIF-1-alpha transcription factor network	96	7370	76	-0.048	0.096	1000	-1000	0	-1000
Ephrin B reverse signaling	96	4651	48	-0.2	0.08	1000	-1000	-0.056	-1000
Wnt signaling	96	678	7	-0.019	0.041	1000	-1000	0.005	-1000
Osteopontin-mediated events	91	3471	38	-0.18	0.041	1000	-1000	-0.015	-1000
LPA receptor mediated events	91	9347	102	-0.047	0.041	1000	-1000	-0.058	-1000
PDGFR-alpha signaling pathway	88	3877	44	-0.12	0.05	1000	-1000	-0.02	-1000
Endothelins	88	8525	96	-0.18	0.044	1000	-1000	-0.02	-1000
Syndecan-1-mediated signaling events	87	2966	34	-0.036	0.04	1000	-1000	-0.005	-1000
Nectin adhesion pathway	84	5306	63	-0.083	0.062	1000	-1000	-0.005	-1000
amb2 Integrin signaling	82	6727	82	-0.083	0.082	1000	-1000	-0.012	-1000
TCGA08_retinoblastoma	82	662	8	-0.012	0.029	1000	-1000	-0.005	-1000
TRAIL signaling pathway	81	3912	48	-0.022	0.042	1000	-1000	-0.017	-1000
Nongenotropic Androgen signaling	78	4060	52	-0.12	0.061	1000	-1000	-0.016	-1000
Thromboxane A2 receptor signaling	76	8061	105	-0.15	0.071	1000	-1000	-0.021	-1000
BARD1 signaling events	75	4322	57	-0.038	0.064	1000	-1000	-0.063	-1000
TCGA08_rtk_signaling	73	1916	26	-0.017	0.04	1000	-1000	-0.019	-1000
Paxillin-dependent events mediated by a4b1	71	2562	36	-0.066	0.069	1000	-1000	-0.054	-1000
Signaling events mediated by the Hedgehog family	69	3620	52	-0.065	0.058	1000	-1000	-0.025	-1000
IL1-mediated signaling events	69	4308	62	-0.045	0.073	1000	-1000	-0.017	-1000
Integrins in angiogenesis	69	5809	84	-0.057	0.056	1000	-1000	-0.017	-1000
Ras signaling in the CD4+ TCR pathway	69	1189	17	-0.002	0.054	1000	-1000	0	-1000
IL6-mediated signaling events	68	5163	75	-0.14	0.05	1000	-1000	-0.029	-1000
Syndecan-4-mediated signaling events	68	4615	67	-0.06	0.046	1000	-1000	-0.032	-1000
Fc-epsilon receptor I signaling in mast cells	67	6572	97	-0.072	0.046	1000	-1000	-0.043	-1000
IL23-mediated signaling events	67	4069	60	-0.16	0.055	1000	-1000	-0.02	-1000
Signaling events mediated by PRL	66	2250	34	-0.018	0.04	1000	-1000	-0.024	-1000
Cellular roles of Anthrax toxin	65	2544	39	-0.078	0.04	1000	-1000	-0.015	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	65	5550	85	-0.16	0.051	1000	-1000	-0.028	-1000
Signaling events mediated by PTP1B	65	4990	76	-0.058	0.07	1000	-1000	-0.023	-1000
Canonical Wnt signaling pathway	64	3310	51	-0.18	0.099	1000	-1000	-0.024	-1000
IGF1 pathway	64	3668	57	-0.022	0.065	1000	-1000	-0.012	-1000
Noncanonical Wnt signaling pathway	63	1644	26	-0.032	0.041	1000	-1000	-0.017	-1000
FoxO family signaling	63	4033	64	-0.2	0.046	1000	-1000	-0.025	-1000
E-cadherin signaling in keratinocytes	63	2742	43	-0.026	0.05	1000	-1000	-0.006	-1000
IL2 signaling events mediated by STAT5	61	1359	22	-0.039	0.047	1000	-1000	-0.004	-1000
IL4-mediated signaling events	60	5519	91	-0.23	0.058	1000	-1000	-0.03	-1000
BMP receptor signaling	60	4883	81	-0.02	0.07	1000	-1000	-0.003	-1000
IFN-gamma pathway	60	4124	68	-0.058	0.063	1000	-1000	-0.033	-1000
IL12-mediated signaling events	59	5185	87	-0.19	0.061	1000	-1000	-0.025	-1000
a4b1 and a4b7 Integrin signaling	59	295	5	0.033	0.039	1000	-1000	0.037	-1000
EPHB forward signaling	59	5020	85	-0.055	0.16	1000	-1000	-0.038	-1000
TCR signaling in naïve CD8+ T cells	58	5482	93	-0.082	0.087	1000	-1000	-0.02	-1000
E-cadherin signaling events	56	280	5	0.035	0.049	1000	-1000	0.038	-1000
Paxillin-independent events mediated by a4b1 and a4b7	55	2053	37	-0.02	0.07	1000	-1000	-0.016	-1000
FAS signaling pathway (CD95)	55	2618	47	-0.058	0.052	1000	-1000	-0.026	-1000
BCR signaling pathway	54	5362	99	-0.075	0.069	1000	-1000	-0.022	-1000
Retinoic acid receptors-mediated signaling	53	3093	58	-0.079	0.06	1000	-1000	-0.006	-1000
E-cadherin signaling in the nascent adherens junction	53	4070	76	-0.057	0.071	1000	-1000	-0.032	-1000
Syndecan-2-mediated signaling events	52	3641	69	0	0.063	1000	-1000	-0.012	-1000
Plasma membrane estrogen receptor signaling	52	4489	86	-0.09	0.086	1000	-1000	-0.022	-1000
Presenilin action in Notch and Wnt signaling	51	3115	61	-0.16	0.075	1000	-1000	-0.03	-1000
Class I PI3K signaling events	50	3654	73	-0.015	0.05	1000	-1000	-0.017	-1000
ErbB4 signaling events	49	3439	69	-0.07	0.056	1000	-1000	-0.03	-1000
IL2 signaling events mediated by PI3K	49	2866	58	-0.064	0.041	1000	-1000	-0.034	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	49	2216	45	-0.058	0.075	1000	-1000	-0.016	-1000
Circadian rhythm pathway	48	1071	22	-0.081	0.044	1000	-1000	-0.023	-1000
HIF-2-alpha transcription factor network	48	2076	43	-0.061	0.069	1000	-1000	-0.077	-1000
Aurora B signaling	48	3257	67	-0.058	0.067	1000	-1000	-0.011	-1000
Caspase cascade in apoptosis	47	3534	74	-0.11	0.051	1000	-1000	-0.018	-1000
LPA4-mediated signaling events	46	552	12	-0.015	0.054	1000	-1000	-0.014	-1000
Reelin signaling pathway	46	2624	56	-0.011	0.095	1000	-1000	-0.008	-1000
Arf6 signaling events	45	2842	62	0	0.082	1000	-1000	0	-1000
EPO signaling pathway	45	2511	55	0	0.072	1000	-1000	-0.012	-1000
PLK1 signaling events	45	3861	85	-0.046	0.051	1000	-1000	-0.012	-1000
Stabilization and expansion of the E-cadherin adherens junction	45	3371	74	-0.076	0.066	1000	-1000	-0.052	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	45	1509	33	-0.005	0.086	1000	-1000	-0.006	-1000
Regulation of Telomerase	44	4540	102	-0.11	0.071	1000	-1000	-0.016	-1000
Regulation of Androgen receptor activity	43	3025	70	-0.081	0.064	1000	-1000	-0.024	-1000
Canonical NF-kappaB pathway	42	1642	39	-0.036	0.065	1000	-1000	-0.017	-1000
p75(NTR)-mediated signaling	42	5318	125	-0.059	0.099	1000	-1000	-0.037	-1000
RXR and RAR heterodimerization with other nuclear receptor	42	2184	52	-0.038	0.095	1000	-1000	-0.017	-1000
Regulation of p38-alpha and p38-beta	41	2258	54	-0.029	0.091	1000	-1000	-0.002	-1000
ErbB2/ErbB3 signaling events	40	2630	65	-0.033	0.047	1000	-1000	-0.029	-1000
EGFR-dependent Endothelin signaling events	40	858	21	-0.016	0.081	1000	-1000	-0.005	-1000
Neurotrophic factor-mediated Trk receptor signaling	39	4726	120	-0.052	0.09	1000	-1000	-0.022	-1000
Arf6 downstream pathway	38	1651	43	-0.034	0.061	1000	-1000	-0.045	-1000
Insulin-mediated glucose transport	38	1229	32	-0.018	0.047	1000	-1000	-0.017	-1000
mTOR signaling pathway	38	2042	53	-0.053	0.057	1000	-1000	-0.017	-1000
Signaling mediated by p38-gamma and p38-delta	38	572	15	-0.038	0.039	1000	-1000	-0.017	-1000
p38 MAPK signaling pathway	38	1710	44	-0.043	0.072	1000	-1000	0	-1000
Aurora A signaling	37	2234	60	-0.046	0.066	1000	-1000	-0.017	-1000
PDGFR-beta signaling pathway	37	3656	97	-0.036	0.083	1000	-1000	-0.032	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	36	1963	54	-0.017	0.056	1000	-1000	-0.018	-1000
ceramide signaling pathway	36	1806	49	-0.032	0.059	1000	-1000	-0.009	-1000
Syndecan-3-mediated signaling events	36	1276	35	-0.013	0.073	1000	-1000	-0.01	-1000
Regulation of nuclear SMAD2/3 signaling	34	4659	136	-0.091	0.1	1000	-1000	-0.056	-1000
Class I PI3K signaling events mediated by Akt	34	2328	68	-0.034	0.078	1000	-1000	-0.018	-1000
Atypical NF-kappaB pathway	34	1076	31	-0.016	0.041	1000	-1000	-0.018	-1000
S1P3 pathway	34	1435	42	-0.02	0.054	1000	-1000	-0.009	-1000
Class IB PI3K non-lipid kinase events	34	102	3	-0.039	0.039	1000	-1000	-0.037	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	33	771	23	-0.017	0.066	1000	-1000	-0.006	-1000
JNK signaling in the CD4+ TCR pathway	33	572	17	-0.007	0.079	1000	-1000	-0.007	-1000
Hedgehog signaling events mediated by Gli proteins	33	2199	65	0	0.076	1000	-1000	-0.008	-1000
FOXA2 and FOXA3 transcription factor networks	33	1555	46	-0.12	0.056	1000	-1000	-0.009	-1000
Signaling events mediated by HDAC Class I	33	3465	104	-0.041	0.076	1000	-1000	-0.041	-1000
S1P4 pathway	33	829	25	-0.013	0.054	1000	-1000	-0.008	-1000
Ephrin A reverse signaling	32	229	7	-0.013	0.04	1000	-1000	-0.008	-1000
S1P5 pathway	32	559	17	-0.007	0.041	1000	-1000	-0.019	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	32	2715	83	-0.013	0.071	1000	-1000	-0.016	-1000
Coregulation of Androgen receptor activity	30	2281	76	-0.011	0.052	1000	-1000	-0.009	-1000
Glypican 1 network	30	1459	48	-0.04	0.069	1000	-1000	-0.038	-1000
Sphingosine 1-phosphate (S1P) pathway	29	820	28	-0.019	0.054	1000	-1000	-0.017	-1000
Signaling events regulated by Ret tyrosine kinase	29	2414	82	-0.009	0.092	1000	-1000	-0.02	-1000
Signaling events mediated by VEGFR1 and VEGFR2	29	3674	125	-0.023	0.072	1000	-1000	-0.017	-1000
Ceramide signaling pathway	28	2182	76	-0.019	0.081	1000	-1000	-0.017	-1000
Alternative NF-kappaB pathway	28	366	13	0	0.094	1000	-1000	0	-1000
Nephrin/Neph1 signaling in the kidney podocyte	27	936	34	-0.049	0.086	1000	-1000	-0.046	-1000
Insulin Pathway	27	2002	74	-0.026	0.1	1000	-1000	-0.027	-1000
Signaling events mediated by HDAC Class II	26	1957	75	-0.036	0.094	1000	-1000	-0.025	-1000
IL27-mediated signaling events	26	1338	51	-0.008	0.08	1000	-1000	-0.024	-1000
Angiopoietin receptor Tie2-mediated signaling	26	2296	88	-0.045	0.076	1000	-1000	-0.045	-1000
Glucocorticoid receptor regulatory network	25	2927	114	-0.11	0.077	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class III	25	1023	40	-0.064	0.072	1000	-1000	-0.052	-1000
Calcium signaling in the CD4+ TCR pathway	25	792	31	-0.039	0.084	1000	-1000	-0.014	-1000
Signaling mediated by p38-alpha and p38-beta	24	1073	44	-0.023	0.055	1000	-1000	-0.007	-1000
VEGFR1 specific signals	24	1366	56	-0.027	0.045	1000	-1000	-0.024	-1000
Arf1 pathway	24	1306	54	-0.01	0.052	1000	-1000	-0.009	-1000
Sumoylation by RanBP2 regulates transcriptional repression	23	623	27	-0.031	0.083	1000	-1000	-0.025	-1000
S1P1 pathway	22	812	36	-0.001	0.044	1000	-1000	-0.014	-1000
Effects of Botulinum toxin	21	560	26	-0.01	0.071	1000	-1000	-0.009	-1000
Rapid glucocorticoid signaling	21	430	20	-0.01	0.049	1000	-1000	-0.009	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	19	1319	68	-0.078	0.095	1000	-1000	-0.042	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	19	1489	78	-0.021	0.065	1000	-1000	-0.027	-1000
Aurora C signaling	18	129	7	0	0.063	1000	-1000	-0.001	-1000
Glypican 2 network	18	72	4	0.04	0.055	1000	-1000	0.038	-1000
Arf6 trafficking events	18	1287	71	-0.047	0.05	1000	-1000	-0.038	-1000
Visual signal transduction: Cones	15	605	38	-0.01	0.088	1000	-1000	-0.009	-1000
Visual signal transduction: Rods	14	741	52	-0.018	0.098	1000	-1000	-0.003	-1000
Total	6553	359135	7203	-7.1	8.4	131000	-131000	-2.5	-131000

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.026	0.02	-9999	0	0	215	215
PLK4	0.036	0.015	-9999	0	0	83	83
regulation of centriole replication	-0.011	0.01	0	263	-9999	0	263

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.35	0.6	-10000	0	-1.2	165	165
PLK1	-0.048	0.31	-10000	0	-1.2	34	34
BIRC5	-0.053	0.32	-10000	0	-1.3	35	35
HSPA1B	-0.36	0.6	-10000	0	-1.1	176	176
MAP2K1	0.002	0.07	-10000	0	-10000	0	0
BRCA2	-0.36	0.61	-10000	0	-1.2	167	167
FOXM1	-0.52	0.88	-10000	0	-1.6	174	174
XRCC1	-0.35	0.6	-10000	0	-1.2	166	166
FOXM1B/p19	-0.44	0.66	-10000	0	-1.3	178	178
Cyclin D1/CDK4	-0.36	0.55	-10000	0	-1	180	180
CDC2	-0.42	0.68	-10000	0	-1.3	182	182
TGFA	-0.32	0.52	-10000	0	-0.98	175	175
SKP2	-0.35	0.61	-10000	0	-1.2	168	168
CCNE1	0.02	0.029	-10000	0	-0.009	255	255
CKS1B	-0.35	0.61	-10000	0	-1.2	168	168
RB1	-0.32	0.48	-10000	0	-0.97	170	170
FOXM1C/SP1	-0.44	0.71	-10000	0	-1.3	179	179
AURKB	-0.1	0.4	-10000	0	-1.2	61	61
CENPF	-0.39	0.63	-10000	0	-1.2	187	187
CDK4	0.007	0.044	0.11	3	-0.039	166	169
MYC	-0.34	0.48	-10000	0	-0.95	183	183
CHEK2	0.005	0.065	-10000	0	-10000	0	0
ONECUT1	-0.36	0.58	-10000	0	-1.1	177	177
CDKN2A	0.026	0.02	0.089	2	-0.034	8	10
LAMA4	-0.39	0.63	-10000	0	-1.2	187	187
FOXM1B/HNF6	-0.46	0.71	-10000	0	-1.4	177	177
FOS	-0.43	0.65	-10000	0	-1.2	219	219
SP1	0.036	0.022	-10000	0	-0.033	47	47
CDC25B	-0.35	0.61	-10000	0	-1.1	169	169
response to radiation	-0.006	0.036	0.088	9	-10000	0	9
CENPB	-0.34	0.6	-10000	0	-1.2	162	162
CENPA	-0.36	0.6	-10000	0	-1.1	170	170
NEK2	-0.37	0.62	-10000	0	-1.2	173	173
HIST1H2BA	-0.35	0.6	-10000	0	-1.1	168	168
CCNA2	0.024	0.029	-10000	0	-0.011	202	202
EP300	0.036	0.014	-10000	0	0	73	73
CCNB1/CDK1	-0.49	0.79	-10000	0	-1.5	175	175
CCNB2	-0.38	0.63	0.8	1	-1.2	181	182
CCNB1	-0.39	0.66	-10000	0	-1.3	173	173
ETV5	-0.37	0.64	-10000	0	-1.2	193	193
ESR1	-0.4	0.62	-10000	0	-1.1	190	190
CCND1	-0.37	0.55	-10000	0	-1	186	186
GSK3A	0.005	0.062	0.15	3	-10000	0	3
Cyclin A-E1/CDK1-2	-0.007	0.11	-10000	0	-0.17	125	125
CDK2	0.029	0.028	-10000	0	-0.018	129	129
G2/M transition of mitotic cell cycle	-0.007	0.044	0.095	10	-10000	0	10
FOXM1B/Cbp/p300	-0.41	0.66	-10000	0	-1.3	175	175
GAS1	-0.36	0.6	-10000	0	-1.1	174	174
MMP2	-0.43	0.65	-10000	0	-1.2	219	219
RB1/FOXM1C	-0.41	0.59	0.67	1	-1.1	187	188
CREBBP	0.038	0.012	-10000	0	0	54	54

×

TCGA08_p53

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
CDKN2A	-0.007	0.005	0	175	-10000	0	175
TP53	-0.053	0.12	0.18	13	-0.24	149	162
Senescence	-0.063	0.12	0.18	13	-0.24	151	164
Apoptosis	-0.063	0.12	0.18	13	-0.24	151	164
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.006	0.038	0.3	8	-10000	0	8
MDM4	0.038	0.013	-10000	0	0	57	57

×

HIF-1-alpha transcription factor network

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
PKM2	0.034	0.34	0.55	49	-0.53	90	139
HDAC7	-0.001	0.004	-10000	0	-0.037	1	1
HIF1A/ARNT/Cbp/p300/Src-1	0.03	0.32	0.6	3	-0.59	54	57
SMAD4	0.039	0.012	-10000	0	0	49	49
ID2	0.034	0.33	0.55	50	-0.52	89	139
AP1	0.006	0.085	-10000	0	-0.14	120	120
ABCG2	0.029	0.33	0.56	44	-0.53	89	133
HIF1A	0.031	0.1	0.2	42	-0.13	88	130
TFF3	0.01	0.32	0.55	36	-0.53	87	123
GATA2	0.04	0.019	-10000	0	-0.058	12	12
AKT1	0.042	0.097	0.22	34	-0.11	70	104
response to hypoxia	0.006	0.069	0.15	41	-0.11	47	88
MCL1	0.036	0.34	0.55	47	-0.53	90	137
NDRG1	-0.017	0.29	0.53	27	-0.56	76	103
SERPINE1	-0.01	0.3	0.55	27	-0.53	87	114
FECH	0.031	0.33	0.55	51	-0.53	87	138
FURIN	0.037	0.34	0.55	49	-0.52	90	139
NCOA2	0.038	0.015	-10000	0	-0.001	72	72
EP300	0.045	0.12	0.29	39	-0.24	20	59
HMOX1	0.021	0.33	0.55	43	-0.53	92	135
BHLHE40	-0.024	0.3	0.5	41	-0.52	90	131
BHLHE41	-0.024	0.3	0.5	41	-0.52	90	131
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.096	0.16	0.36	17	-0.19	43	60
ENG	0.02	0.11	0.27	15	-0.2	27	42
JUN	0.036	0.019	-10000	0	-0.005	90	90
RORA	0.034	0.33	0.55	48	-0.52	90	138
ABCB1	0.018	0.097	-10000	0	-0.55	4	4
TFRC	-0.007	0.31	0.55	33	-0.54	86	119
CXCR4	0.009	0.33	0.55	40	-0.53	95	135
TF	0.027	0.33	0.55	47	-0.52	88	135
CITED2	0.032	0.33	0.54	49	-0.52	91	140
HIF1A/ARNT	0.018	0.38	-10000	0	-0.65	63	63
LDHA	-0.048	0.3	-10000	0	-0.9	55	55
ETS1	0.011	0.33	0.54	35	-0.54	91	126
PGK1	0.032	0.34	0.55	50	-0.54	92	142
NOS2	-0.024	0.3	0.5	41	-0.52	90	131
ITGB2	0.012	0.34	0.55	42	-0.55	93	135
ALDOA	0.041	0.34	0.55	50	-0.53	89	139
Cbp/p300/CITED2	0.014	0.34	0.56	27	-0.59	75	102
FOS	0.027	0.022	-10000	0	-0.049	5	5
HK2	0.035	0.34	0.55	47	-0.53	89	136
SP1	0.048	0.008	-10000	0	-10000	0	0
GCK	0.066	0.15	0.53	5	-10000	0	5
HK1	0.034	0.34	0.54	51	-0.53	90	141
NPM1	0.039	0.34	0.55	50	-0.53	90	140
EGLN1	0.04	0.33	0.55	50	-0.53	84	134
CREB1	0.035	0.041	-10000	0	-0.11	41	41
PGM1	0.027	0.34	0.55	45	-0.54	90	135
SMAD3	0.041	0.009	-10000	0	0	24	24
EDN1	0.035	0.21	0.46	4	-1	13	17
IGFBP1	0.04	0.34	0.55	48	-0.53	88	136
VEGFA	-0.007	0.26	0.47	33	-0.48	71	104
HIF1A/JAB1	0.035	0.099	0.2	9	-0.15	75	84
CP	-0.013	0.32	0.53	34	-0.55	88	122
CXCL12	-0.019	0.31	0.54	28	-0.53	94	122
COPS5	0.036	0.016	-10000	0	-0.001	87	87
SMAD3/SMAD4	0.052	0.034	-10000	0	-0.14	12	12
BNIP3	0.017	0.33	0.55	42	-0.54	90	132
EGLN3	-0.017	0.32	0.54	31	-0.55	96	127
CA9	-0.016	0.3	0.55	24	-0.53	88	112
TERT	0.022	0.32	0.54	42	-0.53	86	128
ENO1	0.035	0.34	0.55	49	-0.53	90	139
PFKL	0.037	0.34	0.55	47	-0.53	88	135
NCOA1	0.04	0.01	-10000	0	-0.001	29	29
ADM	-0.001	0.32	0.54	26	-0.53	91	117
ARNT	0.031	0.098	0.2	39	-0.12	86	125
HNF4A	0.041	0.013	-10000	0	-10000	0	0
ADFP	-0.002	0.32	0.54	36	-0.53	95	131
SLC2A1	0.005	0.28	0.49	24	-0.52	69	93
LEP	0.039	0.33	0.55	49	-0.53	86	135
HIF1A/ARNT/Cbp/p300	0.015	0.32	0.61	2	-0.61	54	56
EPO	0.03	0.28	0.51	24	-0.5	62	86
CREBBP	0.05	0.11	0.29	44	-0.22	14	58
HIF1A/ARNT/Cbp/p300/HDAC7	0.005	0.31	-10000	0	-0.6	57	57
PFKFB3	0.029	0.34	0.55	47	-0.54	89	136
NT5E	-0.036	0.31	0.54	21	-0.55	98	119

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.031	0.018	-10000	0	0	143	143
EPHB2	0.043	0.013	0.067	2	0	38	40
EFNB1	-0.001	0.024	0.029	210	-10000	0	210
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.077	0.066	0.23	1	-0.12	19	20
Ephrin B2/EPHB1-2	0.041	0.069	-10000	0	-0.1	77	77
neuron projection morphogenesis	0.052	0.052	-10000	0	-0.11	23	23
Ephrin B1/EPHB1-2/Tiam1	0.07	0.061	0.21	3	-0.11	29	32
DNM1	0.041	0.012	-10000	0	0	38	38
cell-cell signaling	0.003	0.006	0.024	2	-10000	0	2
MAP2K4	-0.13	0.21	0.23	3	-0.46	164	167
YES1	-0.2	0.33	-10000	0	-0.69	168	168
Ephrin B1/EPHB1-2/NCK2	0.08	0.052	0.21	3	-0.11	17	20
PI3K	-0.1	0.22	-10000	0	-0.44	167	167
mol:GDP	0.068	0.06	0.2	3	-0.11	29	32
ITGA2B	0.04	0.009	-10000	0	0	30	30
endothelial cell proliferation	0.024	0.061	-10000	0	-0.11	83	83
FYN	-0.2	0.33	-10000	0	-0.7	166	166
MAP3K7	-0.13	0.23	0.22	4	-0.48	160	164
FGR	-0.19	0.32	-10000	0	-0.68	171	171
TIAM1	0.037	0.014	-10000	0	0	72	72
PIK3R1	0.034	0.017	-10000	0	0	108	108
RGS3	0.04	0.008	-10000	0	0	23	23
cell adhesion	-0.11	0.21	-10000	0	-0.41	167	167
LYN	-0.19	0.32	-10000	0	-0.69	163	163
Ephrin B1/EPHB1-2/Src Family Kinases	-0.18	0.3	-10000	0	-0.62	170	170
Ephrin B1/EPHB1-2	-0.14	0.24	-10000	0	-0.53	151	151
SRC	-0.18	0.32	-10000	0	-0.68	166	166
ITGB3	0.033	0.017	-10000	0	0	121	121
EPHB1	0.04	0.014	-10000	0	0	59	59
EPHB4	0.04	0.009	-10000	0	0	29	29
RAC1	0.039	0.01	-10000	0	0	34	34
Ephrin B2/EPHB4	0.025	0.061	-10000	0	-0.11	83	83
alphaIIb/beta3 Integrin	0.04	0.05	-10000	0	-0.14	34	34
BLK	-0.19	0.32	-10000	0	-0.69	165	165
HCK	-0.19	0.32	-10000	0	-0.68	165	165
regulation of stress fiber formation	-0.077	0.051	0.11	17	-0.22	2	19
MAPK8	-0.14	0.21	0.24	1	-0.44	168	169
Ephrin B1/EPHB1-2/RGS3	0.08	0.052	0.21	4	-0.11	18	22
endothelial cell migration	-0.11	0.18	0.19	5	-0.4	146	151
NCK2	0.042	0.004	-10000	0	0	6	6
PTPN13	0.022	0.022	-10000	0	0	276	276
regulation of focal adhesion formation	-0.077	0.051	0.11	17	-0.22	2	19
chemotaxis	-0.077	0.051	0.11	18	-0.2	4	22
PIK3CA	0.03	0.019	-10000	0	0	155	155
Rac1/GTP	0.066	0.059	0.2	1	-0.12	21	22
angiogenesis	-0.14	0.24	-10000	0	-0.52	157	157
LCK	-0.19	0.32	-10000	0	-0.68	170	170

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.019	0.096	-9999	-0.2	94	94
FZD6	0.029	0.019	-9999	0	170	170
WNT6	0.041	0.006	-9999	0	13	13
WNT4	0.041	0.007	-9999	0	18	18
FZD3	0.029	0.019	-9999	0	168	168
WNT5A	0.035	0.015	-9999	0	91	91
WNT11	0.033	0.017	-9999	0	124	124

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.011	0.13	0.2	10	-0.22	121	131
NF kappa B1 p50/RelA/I kappa B alpha	-0.048	0.18	0.28	1	-0.35	124	125
alphaV/beta3 Integrin/Osteopontin/Src	-0.007	0.11	-10000	0	-0.16	155	155
AP1	-0.044	0.18	0.27	2	-0.28	154	156
ILK	-0.027	0.11	0.19	11	-0.24	71	82
bone resorption	-0.04	0.1	0.2	2	-0.25	59	61
PTK2B	0.033	0.017	-10000	0	0	118	118
PYK2/p130Cas	0.005	0.12	-10000	0	-0.19	88	88
ITGAV	0.026	0.033	-10000	0	-0.048	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.029	0.068	-10000	0	-0.14	68	68
alphaV/beta3 Integrin/Osteopontin	0.005	0.13	-10000	0	-0.17	163	163
MAP3K1	-0.027	0.1	0.19	11	-0.24	69	80
JUN	0.036	0.015	-10000	0	0	80	80
MAPK3	-0.047	0.14	0.19	13	-0.28	112	125
MAPK1	-0.046	0.14	0.19	13	-0.28	111	124
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
NFKB1	0.036	0.015	-10000	0	0	84	84
MAPK8	-0.032	0.1	0.17	13	-0.23	77	90
ITGB3	0.023	0.034	-10000	0	-0.048	76	76
NFKBIA	-0.064	0.16	0.19	10	-0.36	110	120
FOS	0.027	0.021	-10000	0	0	207	207
CD44	0.035	0.016	-10000	0	0	96	96
CHUK	0.038	0.012	-10000	0	0	52	52
PLAU	-0.18	0.42	-10000	0	-1	107	107
NF kappa B1 p50/RelA	-0.032	0.2	-10000	0	-0.39	109	109
BCAR1	0.036	0.014	-10000	0	0	76	76
RELA	0.041	0.006	-10000	0	0	10	10
alphaV beta3 Integrin	0.004	0.091	-10000	0	-0.14	136	136
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.029	0.1	0.19	12	-0.23	72	84
VAV3	-0.039	0.1	0.17	11	-0.23	89	100
MAP3K14	-0.024	0.12	0.2	13	-0.23	108	121
ROCK2	0.037	0.013	-10000	0	0	65	65
SPP1	0.025	0.031	-10000	0	-0.05	51	51
RAC1	0.039	0.01	-10000	0	0	34	34
Rac1/GTP	-0.034	0.11	0.18	11	-0.22	88	99
MMP2	-0.088	0.14	0.2	1	-0.31	131	132

×

LPA receptor mediated events

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
GNB1/GNG2	0.021	0.081	-10000	0	-0.14	111	111
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.11	0.21	3	-0.22	72	75
AP1	-0.026	0.068	-10000	0	-0.12	172	172
mol:PIP3	-0.036	0.057	-10000	0	-0.13	126	126
AKT1	-0.002	0.094	0.24	18	-0.24	15	33
PTK2B	-0.047	0.11	0.12	3	-0.19	183	186
RHOA	0.002	0.058	0.17	1	-0.3	8	9
PIK3CB	0.034	0.016	-10000	0	0	103	103
mol:Ca2+	-0.008	0.048	0.19	8	-0.14	19	27
MAGI3	0.04	0.009	-10000	0	0	30	30
RELA	0.041	0.006	-10000	0	0	10	10
apoptosis	0.002	0.069	0.072	123	-0.14	95	218
HRAS/GDP	0.029	0.01	-10000	0	-0.13	1	1
positive regulation of microtubule depolymerization	-0.046	0.1	0.19	16	-0.2	125	141
NF kappa B1 p50/RelA	-0.028	0.076	0.11	2	-0.16	113	115
endothelial cell migration	-0.04	0.12	-10000	0	-0.3	99	99
ADCY4	-0.019	0.094	0.16	2	-0.2	99	101
ADCY5	-0.018	0.092	0.16	2	-0.19	103	105
ADCY6	-0.019	0.094	0.17	1	-0.2	103	104
ADCY7	-0.018	0.092	0.16	2	-0.19	100	102
ADCY1	-0.018	0.092	0.16	2	-0.2	99	101
ADCY2	-0.014	0.09	0.17	1	-0.2	90	91
ADCY3	-0.02	0.094	0.17	1	-0.2	105	106
ADCY8	-0.002	0.086	0.17	1	-0.19	77	78
ADCY9	-0.022	0.098	0.16	2	-0.2	107	109
GSK3B	-0.046	0.11	0.21	15	-0.18	179	194
arachidonic acid secretion	-0.029	0.098	0.14	2	-0.19	123	125
GNG2	0.039	0.01	-10000	0	0	34	34
TRIP6	0.012	0.052	-10000	0	-0.24	19	19
GNAO1	0.006	0.071	0.09	116	-0.14	92	208
HRAS	0.04	0.01	-10000	0	0	31	31
NFKBIA	-0.03	0.091	0.17	9	-0.24	57	66
GAB1	0.038	0.012	-10000	0	0	52	52
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.011	0.26	-10000	0	-0.87	47	47
JUN	0.036	0.015	-10000	0	0	80	80
LPA/LPA2/NHERF2	0.015	0.037	-10000	0	-0.061	94	94
TIAM1	-0.037	0.3	-10000	0	-1	47	47
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	-0.004	0.044	0.19	8	-0.14	15	23
PLCB3	0.016	0.044	0.16	13	-0.062	91	104
FOS	0.026	0.02	-10000	0	0	207	207
positive regulation of mitosis	-0.029	0.098	0.14	2	-0.19	123	125
LPA/LPA1-2-3	-0.017	0.049	-10000	0	-0.12	100	100
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.036	0.014	-10000	0	0	76	76
stress fiber formation	-0.011	0.1	-10000	0	-0.25	46	46
GNAZ	0.008	0.073	0.091	122	-0.15	87	209
EGFR/PI3K-beta/Gab1	-0.025	0.066	-10000	0	-0.13	127	127
positive regulation of dendritic cell cytokine production	-0.017	0.049	-10000	0	-0.12	100	100
LPA/LPA2/MAGI-3	0.016	0.037	-10000	0	-0.061	95	95
ARHGEF1	0.006	0.076	0.2	12	-0.13	94	106
GNAI2	0.006	0.076	0.091	126	-0.14	99	225
GNAI3	0.004	0.079	0.091	122	-0.15	98	220
GNAI1	0.003	0.079	0.091	119	-0.16	94	213
LPA/LPA3	-0.01	0.026	-10000	0	-0.065	100	100
LPA/LPA2	-0.01	0.025	-10000	0	-0.065	100	100
LPA/LPA1	-0.024	0.067	-10000	0	-0.17	100	100
HB-EGF/EGFR	0.023	0.052	-10000	0	-0.13	48	48
HBEGF	-0.013	0.01	-10000	0	-10000	0	0
mol:DAG	-0.004	0.044	0.19	8	-0.14	15	23
cAMP biosynthetic process	-0.023	0.097	0.18	4	-0.2	97	101
NFKB1	0.036	0.015	-10000	0	0	84	84
SRC	0.039	0.01	-10000	0	0	36	36
GNB1	0.041	0.005	-10000	0	0	7	7
LYN	-0.024	0.094	0.18	10	-0.23	60	70
GNAQ	0.009	0.032	0.043	124	-0.053	101	225
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.017	0.04	-10000	0	-0.1	100	100
IL8	-0.023	0.18	0.26	4	-0.37	91	95
PTK2	0.006	0.061	0.094	80	-0.13	75	155
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
CASP3	0.002	0.069	0.072	123	-0.14	95	218
EGFR	0.037	0.014	-10000	0	0	72	72
PLCG1	0.006	0.037	-10000	0	-0.098	30	30
PLD2	0.016	0.066	0.094	124	-0.12	90	214
G12/G13	0.023	0.078	-10000	0	-0.14	100	100
PI3K-beta	-0.025	0.074	-10000	0	-0.21	42	42
cell migration	-0.008	0.086	-10000	0	-0.24	46	46
SLC9A3R2	0.038	0.012	-10000	0	0	53	53
PXN	-0.011	0.1	-10000	0	-0.25	46	46
HRAS/GTP	-0.029	0.099	0.14	2	-0.2	121	123
RAC1	0.039	0.01	-10000	0	0	34	34
MMP9	0.029	0.02	-10000	0	0	178	178
PRKCE	0.039	0.01	-10000	0	0	36	36
PRKCD	-0.016	0.054	0.18	11	-0.16	19	30
Gi(beta/gamma)	-0.02	0.1	0.16	1	-0.19	119	120
mol:LPA	-0.017	0.04	-10000	0	-0.1	100	100
TRIP6/p130 Cas/FAK1/Paxillin	-0.004	0.099	0.19	1	-0.19	83	84
MAPKKK cascade	-0.029	0.098	0.14	2	-0.19	123	125
contractile ring contraction involved in cytokinesis	0.002	0.061	0.17	1	-0.29	10	11
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.032	0.043	125	-0.052	107	232
GNA15	0.009	0.031	0.043	117	-0.054	93	210
GNA12	0.04	0.01	-10000	0	0	32	32
GNA13	0.04	0.009	-10000	0	0	28	28
MAPT	-0.047	0.1	0.19	16	-0.2	127	143
GNA11	0.008	0.032	0.043	118	-0.054	97	215
Rac1/GTP	-0.014	0.28	-10000	0	-0.93	47	47
MMP2	-0.04	0.12	-10000	0	-0.3	99	99

×

PDGFR-alpha signaling pathway

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
PDGFRA	0.018	0.036	-10000	0	-0.054	79	79
PDGF/PDGFRA/CRKL	0.014	0.07	-10000	0	-0.1	126	126
positive regulation of JUN kinase activity	0.048	0.083	-10000	0	-0.11	99	99
CRKL	0.039	0.011	-10000	0	0	38	38
PDGF/PDGFRA/Caveolin-3	0.014	0.072	-10000	0	-0.1	129	129
AP1	-0.12	0.26	-10000	0	-0.65	99	99
mol:IP3	-0.015	0.045	0.065	39	-0.096	81	120
PLCG1	-0.015	0.045	0.065	39	-0.096	81	120
PDGF/PDGFRA/alphaV Integrin	-0.007	0.09	-10000	0	-0.13	164	164
RAPGEF1	0.04	0.008	-10000	0	0	23	23
CRK	0.038	0.012	-10000	0	0	52	52
mol:Ca2+	-0.015	0.045	0.065	39	-0.096	81	120
CAV3	0.04	0.008	-10000	0	0	22	22
CAV1	0.036	0.015	-10000	0	0	80	80
SHC/Grb2/SOS1	0.05	0.084	-10000	0	-0.12	98	98
PDGF/PDGFRA/Shf	0.014	0.071	-10000	0	-0.1	125	125
FOS	-0.12	0.26	0.32	1	-0.64	98	99
JUN	-0.033	0.043	0.23	3	-0.2	11	14
oligodendrocyte development	-0.007	0.09	-10000	0	-0.13	164	164
GRB2	0.041	0.007	-10000	0	0	17	17
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:DAG	-0.015	0.045	0.065	39	-0.096	81	120
PDGF/PDGFRA	0.018	0.036	-10000	0	-0.054	79	79
actin cytoskeleton reorganization	0.015	0.071	-10000	0	-0.1	127	127
SRF	-0.007	0.024	0.033	124	-10000	0	124
SHC1	0.04	0.01	-10000	0	0	31	31
PI3K	0.012	0.08	-10000	0	-0.14	96	96
PDGF/PDGFRA/Crk/C3G	0.036	0.072	-10000	0	-0.12	82	82
JAK1	-0.01	0.02	0.03	23	-10000	0	23
ELK1/SRF	-0.025	0.064	0.15	18	-0.16	56	74
SHB	0.041	0.007	-10000	0	0	17	17
SHF	0.039	0.011	-10000	0	0	41	41
CSNK2A1	0.036	0.031	0.084	1	-0.028	60	61
GO:0007205	-0.025	0.072	0.088	21	-0.19	65	86
SOS1	0.038	0.013	-10000	0	0	56	56
Ras protein signal transduction	0.048	0.083	-10000	0	-0.11	99	99
PDGF/PDGFRA/SHB	0.015	0.071	-10000	0	-0.1	127	127
PDGF/PDGFRA/Caveolin-1	0.012	0.074	-10000	0	-0.11	116	116
ITGAV	0.033	0.017	-10000	0	0	117	117
ELK1	-0.025	0.08	0.2	17	-0.18	65	82
PIK3CA	0.03	0.019	-10000	0	0	155	155
PDGF/PDGFRA/Crk	0.014	0.07	-10000	0	-0.1	120	120
JAK-STAT cascade	-0.01	0.02	0.03	23	-10000	0	23
cell proliferation	0.013	0.07	-10000	0	-0.1	125	125

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.004	0.14	0.23	31	-0.24	115	146
PTK2B	0.033	0.017	-10000	0	0	118	118
mol:Ca2+	-0.032	0.21	-10000	0	-0.55	36	36
EDN1	-0.005	0.1	0.22	8	-0.18	123	131
EDN3	0.036	0.014	-10000	0	0	77	77
EDN2	0.037	0.014	-10000	0	0	66	66
HRAS/GDP	-0.051	0.19	0.27	2	-0.35	112	114
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.026	0.14	0.23	1	-0.26	101	102
ADCY4	0.01	0.14	0.21	66	-0.23	69	135
ADCY5	0.011	0.13	0.21	66	-0.23	68	134
ADCY6	0.008	0.14	0.21	70	-0.24	73	143
ADCY7	0.007	0.14	0.21	64	-0.24	72	136
ADCY1	0.009	0.14	0.21	68	-0.24	71	139
ADCY2	0.01	0.13	0.21	64	-0.23	61	125
ADCY3	0.009	0.14	0.21	69	-0.24	71	140
ADCY8	-0.002	0.11	0.22	33	-0.23	50	83
ADCY9	0.009	0.14	0.21	71	-0.23	74	145
arachidonic acid secretion	-0.1	0.26	0.3	2	-0.49	136	138
ETB receptor/Endothelin-1/Gq/GTP	0	0.11	-10000	0	-0.24	60	60
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.039	0.01	-10000	0	0	31	31
ETA receptor/Endothelin-1/G12/GTP	-0.006	0.13	0.35	7	-0.22	122	129
ETA receptor/Endothelin-1/Gs/GTP	-0.004	0.12	0.32	7	-0.2	119	126
mol:GTP	0	0.006	-10000	0	-0.025	2	2
COL3A1	-0.057	0.16	0.27	7	-0.36	114	121
EDNRB	0.021	0.054	0.096	1	-0.089	96	97
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.003	0.14	0.26	11	-0.26	94	105
CYSLTR1	-0.015	0.15	0.27	8	-0.26	107	115
SLC9A1	-0.016	0.085	0.2	7	-0.17	88	95
mol:GDP	-0.064	0.19	0.26	2	-0.37	112	114
SLC9A3	-0.022	0.19	-10000	0	-0.53	31	31
RAF1	-0.075	0.22	0.28	4	-0.41	135	139
JUN	-0.073	0.3	-10000	0	-0.82	59	59
JAK2	-0.008	0.14	0.23	28	-0.24	114	142
mol:IP3	-0.023	0.14	0.22	1	-0.31	78	79
ETA receptor/Endothelin-1	-0.027	0.15	0.39	6	-0.28	127	133
PLCB1	0.033	0.017	-10000	0	0	114	114
PLCB2	0.037	0.014	-10000	0	-0.005	52	52
ETA receptor/Endothelin-3	0.015	0.084	0.19	7	-0.12	113	120
FOS	-0.14	0.36	0.34	1	-0.83	111	112
Gai/GDP	-0.032	0.24	-10000	0	-0.69	59	59
CRK	0.038	0.012	-10000	0	0	52	52
mol:Ca ++	-0.031	0.19	0.26	25	-0.34	108	133
BCAR1	0.036	0.014	-10000	0	0	76	76
PRKCB1	-0.027	0.14	0.26	4	-0.3	80	84
GNAQ	0.035	0.022	-10000	0	-0.038	31	31
GNAZ	0.039	0.011	-10000	0	0	42	42
GNAL	0.04	0.009	-10000	0	0	26	26
Gs family/GDP	-0.05	0.18	0.27	1	-0.34	106	107
ETA receptor/Endothelin-1/Gq/GTP	-0.015	0.14	0.22	5	-0.26	82	87
MAPK14	-0.017	0.11	0.27	3	-0.25	67	70
TRPC6	-0.034	0.21	-10000	0	-0.57	36	36
GNAI2	0.041	0.007	-10000	0	0	15	15
GNAI3	0.039	0.011	-10000	0	0	45	45
GNAI1	0.035	0.016	-10000	0	0	95	95
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.011	0.11	-10000	0	-0.24	68	68
ETB receptor/Endothelin-2	0.031	0.054	-10000	0	-0.071	91	91
ETB receptor/Endothelin-3	0.032	0.051	-10000	0	-0.067	81	81
ETB receptor/Endothelin-1	0.007	0.11	0.2	5	-0.19	99	104
MAPK3	-0.13	0.34	0.32	2	-0.75	116	118
MAPK1	-0.14	0.35	0.32	2	-0.75	120	122
Rac1/GDP	-0.051	0.18	0.28	1	-0.35	109	110
cAMP biosynthetic process	0.044	0.13	0.24	68	-0.23	27	95
MAPK8	-0.053	0.24	-10000	0	-0.57	70	70
SRC	0.039	0.01	-10000	0	0	36	36
ETB receptor/Endothelin-1/Gi/GTP	-0.011	0.11	-10000	0	-0.27	61	61
p130Cas/CRK/Src/PYK2	-0.059	0.19	0.31	2	-0.41	87	89
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.05	0.19	0.28	1	-0.35	110	111
COL1A2	-0.075	0.21	0.27	5	-0.49	103	108
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.011	0.088	0.19	8	-0.13	127	135
mol:DAG	-0.023	0.14	0.22	1	-0.31	78	79
MAP2K2	-0.099	0.27	0.29	4	-0.55	124	128
MAP2K1	-0.1	0.27	0.3	3	-0.56	124	127
EDNRA	-0.003	0.1	0.22	8	-0.17	133	141
positive regulation of muscle contraction	-0.014	0.12	0.2	29	-0.22	101	130
Gq family/GDP	-0.013	0.19	-10000	0	-0.33	104	104
HRAS/GTP	-0.053	0.18	0.25	2	-0.34	113	115
PRKCH	-0.03	0.14	0.33	1	-0.3	87	88
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCA	-0.031	0.15	0.26	3	-0.31	84	87
PRKCB	-0.027	0.14	0.2	1	-0.29	88	89
PRKCE	-0.028	0.14	0.3	4	-0.3	81	85
PRKCD	-0.031	0.14	0.26	2	-0.31	81	83
PRKCG	-0.034	0.15	-10000	0	-0.31	86	86
regulation of vascular smooth muscle contraction	-0.18	0.44	-10000	0	-1	111	111
PRKCQ	-0.03	0.15	0.29	7	-0.32	78	85
PLA2G4A	-0.11	0.28	0.3	2	-0.54	136	138
GNA14	0.036	0.021	-10000	0	-0.038	32	32
GNA15	0.034	0.022	-10000	0	-0.036	28	28
GNA12	0.04	0.01	-10000	0	0	32	32
GNA11	0.034	0.021	-10000	0	-0.036	29	29
Rac1/GTP	-0.006	0.13	0.35	6	-0.22	120	126
MMP1	0.02	0.12	0.35	16	-0.58	10	26

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.037	0.013	-10000	0	0	62	62
CCL5	0.03	0.019	-10000	0	0	161	161
SDCBP	0.036	0.014	-10000	0	0	75	75
FGFR/FGF2/Syndecan-1	-0.012	0.12	0.2	20	-0.33	42	62
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	-0.013	0.13	0.23	15	-0.3	56	71
Syndecan-1/Syntenin	-0.014	0.14	0.23	19	-0.29	67	86
MAPK3	-0.023	0.13	0.2	18	-0.28	60	78
HGF/MET	0.013	0.075	-10000	0	-0.14	105	105
TGFB1/TGF beta receptor Type II	0.037	0.013	-10000	0	0	62	62
BSG	0.037	0.014	-10000	0	0	71	71
keratinocyte migration	-0.012	0.13	0.23	15	-0.3	56	71
Syndecan-1/RANTES	-0.019	0.14	0.22	17	-0.29	76	93
Syndecan-1/CD147	-0.002	0.15	0.25	13	-0.29	61	74
Syndecan-1/Syntenin/PIP2	-0.016	0.14	0.22	18	-0.28	66	84
LAMA5	0.036	0.015	-10000	0	0	85	85
positive regulation of cell-cell adhesion	-0.016	0.13	0.21	18	-0.28	66	84
MMP7	0.016	0.02	-10000	0	0	340	340
HGF	0.04	0.009	-10000	0	0	29	29
Syndecan-1/CASK	-0.036	0.12	0.15	5	-0.29	63	68
Syndecan-1/HGF/MET	-0.018	0.14	0.26	12	-0.28	74	86
regulation of cell adhesion	-0.031	0.12	0.21	9	-0.29	55	64
HPSE	0.035	0.015	-10000	0	0	90	90
positive regulation of cell migration	-0.012	0.12	0.2	20	-0.33	42	62
SDC1	-0.017	0.12	0.17	5	-0.34	37	42
Syndecan-1/Collagen	-0.012	0.12	0.2	20	-0.33	42	62
PPIB	0.04	0.009	-10000	0	0	24	24
MET	0.027	0.02	-10000	0	0	198	198
PRKACA	0.035	0.015	-10000	0	0	89	89
MMP9	0.029	0.02	-10000	0	0	178	178
MAPK1	-0.022	0.13	0.21	16	-0.28	60	76
homophilic cell adhesion	-0.012	0.13	0.2	28	-0.32	47	75
MMP1	0.03	0.019	-10000	0	0	159	159

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.037	0.013	-10000	0	0	64	64
alphaV beta3 Integrin	0.014	0.079	-10000	0	-0.15	93	93
PTK2	-0.045	0.14	-10000	0	-0.3	104	104
positive regulation of JNK cascade	-0.032	0.14	-10000	0	-0.27	106	106
CDC42/GDP	-0.039	0.2	-10000	0	-0.36	122	122
Rac1/GDP	-0.041	0.19	-10000	0	-0.36	120	120
RAP1B	0.038	0.013	-10000	0	0	59	59
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.04	0.01	-10000	0	0	31	31
CDC42/GTP	-0.037	0.18	-10000	0	-0.34	103	103
nectin-3/I-afadin	0.009	0.077	-10000	0	-0.14	101	101
RAPGEF1	-0.056	0.18	-10000	0	-0.37	124	124
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.063	0.2	-10000	0	-0.4	127	127
PDGFB-D/PDGFRB	0.037	0.013	-10000	0	0	64	64
TLN1	-0.039	0.085	0.19	2	-0.25	60	62
Rap1/GTP	-0.044	0.14	-10000	0	-0.28	127	127
IQGAP1	0.037	0.014	-10000	0	0	69	69
Rap1/GTP/I-afadin	0.042	0.066	-10000	0	-0.11	69	69
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.009	0.077	-10000	0	-0.14	101	101
PVR	0.04	0.009	-10000	0	0	27	27
Necl-5(dimer)	0.04	0.009	-10000	0	0	27	27
mol:GDP	-0.067	0.22	-10000	0	-0.43	123	123
MLLT4	0.034	0.017	-10000	0	0	107	107
PIK3CA	0.03	0.019	-10000	0	0	155	155
PI3K	0.023	0.092	-10000	0	-0.13	100	100
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.041	0.048	-10000	0	-0.14	29	29
positive regulation of lamellipodium assembly	-0.041	0.16	-10000	0	-0.29	123	123
PVRL1	0.04	0.008	-10000	0	0	22	22
PVRL3	0.029	0.019	-10000	0	0	174	174
PVRL2	0.039	0.011	-10000	0	0	44	44
PIK3R1	0.034	0.017	-10000	0	0	108	108
CDH1	0.035	0.016	-10000	0	0	98	98
CLDN1	0.023	0.021	-10000	0	0	259	259
JAM-A/CLDN1	0.013	0.089	-10000	0	-0.12	125	125
SRC	-0.083	0.21	-10000	0	-0.44	132	132
ITGB3	0.033	0.017	-10000	0	0	121	121
nectin-1(dimer)/I-afadin/I-afadin	0.041	0.048	-10000	0	-0.14	29	29
FARP2	-0.059	0.22	-10000	0	-0.44	100	100
RAC1	0.039	0.01	-10000	0	0	34	34
CTNNA1	0.039	0.011	-10000	0	0	38	38
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.023	0.079	-10000	0	-0.12	101	101
nectin-1/I-afadin	0.041	0.048	-10000	0	-0.14	29	29
nectin-2/I-afadin	0.038	0.051	-10000	0	-0.14	34	34
RAC1/GTP/IQGAP1/filamentous actin	0.038	0.046	-10000	0	-0.11	42	42
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.024	0.078	-10000	0	-0.12	96	96
CDC42/GTP/IQGAP1/filamentous actin	0.04	0.047	-10000	0	-0.11	42	42
F11R	0.04	0.01	-10000	0	0	32	32
positive regulation of filopodium formation	-0.032	0.14	-10000	0	-0.27	106	106
alphaV/beta3 Integrin/Talin	-0.031	0.11	0.26	2	-0.22	102	104
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.051	-10000	0	-0.14	34	34
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.051	-10000	0	-0.14	34	34
PIP5K1C	-0.032	0.087	-10000	0	-0.17	121	121
VAV2	-0.075	0.24	-10000	0	-0.47	105	105
RAP1/GDP	-0.039	0.18	-10000	0	-0.34	120	120
ITGAV	0.033	0.017	-10000	0	0	117	117
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.021	0.079	-10000	0	-0.12	102	102
nectin-3(dimer)/I-afadin/I-afadin	0.009	0.077	-10000	0	-0.14	101	101
Rac1/GTP	-0.048	0.19	-10000	0	-0.35	123	123
PTPRM	-0.029	0.097	-10000	0	-0.18	125	125
E-cadherin/beta catenin/alpha catenin	0.062	0.09	-10000	0	-0.13	58	58
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.04	0.009	-10000	0	0	24	24

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.006	0.085	-10000	0	-0.13	126	126
alphaM/beta2 Integrin/GPIbA	0.053	0.069	-10000	0	-0.12	60	60
alphaM/beta2 Integrin/proMMP-9	0.03	0.081	-10000	0	-0.13	83	83
PLAUR	0.036	0.014	-10000	0	0	77	77
HMGB1	0.041	0.016	-10000	0	-0.054	10	10
alphaM/beta2 Integrin/Talin	0.047	0.076	-10000	0	-0.12	74	74
AGER	0.041	0.016	-10000	0	-0.054	10	10
RAP1A	0.039	0.01	-10000	0	0	35	35
SELPLG	0.04	0.009	-10000	0	0	27	27
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.082	0.083	-10000	0	-0.18	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.029	0.02	-10000	0	0	178	178
CYR61	0.03	0.019	-10000	0	0	157	157
TLN1	0.039	0.012	-10000	0	0	46	46
Rap1/GTP	-0.061	0.17	-10000	0	-0.32	132	132
RHOA	0.041	0.007	-10000	0	0	14	14
P-selectin oligomer	0.039	0.011	-10000	0	0	38	38
MYH2	-0.081	0.17	0.2	2	-0.33	137	139
MST1R	0.039	0.011	-10000	0	0	42	42
leukocyte activation during inflammatory response	0.059	0.065	-10000	0	-0.1	51	51
APOB	0.041	0.007	-10000	0	0	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.022	0.021	-10000	0	0	273	273
JAM3	0.038	0.013	-10000	0	0	56	56
GP1BA	0.039	0.01	-10000	0	0	37	37
alphaM/beta2 Integrin/CTGF	0.035	0.081	-10000	0	-0.12	97	97
alphaM/beta2 Integrin	-0.063	0.17	-10000	0	-0.34	122	122
JAM3 homodimer	0.038	0.013	-10000	0	0	56	56
ICAM2	0.039	0.011	-10000	0	0	41	41
ICAM1	0.026	0.02	-10000	0	0	207	207
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.063	0.17	-10000	0	-0.34	123	123
cell adhesion	0.052	0.069	-10000	0	-0.12	60	60
NFKB1	0.022	0.075	0.26	4	-0.22	24	28
THY1	0.025	0.021	-10000	0	0	221	221
RhoA/GDP	0.03	0.012	-10000	0	-0.13	3	3
Lipoprotein(a)	0.05	0.018	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.025	0.1	-10000	0	-0.13	138	138
IL6	-0.019	0.077	0.26	3	-0.43	10	13
ITGB2	0.034	0.022	-10000	0	-0.052	9	9
elevation of cytosolic calcium ion concentration	0.033	0.11	-10000	0	-0.16	105	105
alphaM/beta2 Integrin/JAM2/JAM3	0.067	0.075	-10000	0	-0.11	51	51
JAM2	0.038	0.013	-10000	0	0	57	57
alphaM/beta2 Integrin/ICAM1	0.052	0.1	-10000	0	-0.14	89	89
alphaM/beta2 Integrin/uPA/Plg	0.041	0.099	-10000	0	-0.14	102	102
RhoA/GTP	-0.083	0.18	0.2	1	-0.34	142	143
positive regulation of phagocytosis	-0.04	0.15	0.21	4	-0.3	100	104
Ron/MSP	0.054	0.029	-10000	0	-0.14	9	9
alphaM/beta2 Integrin/uPAR/uPA	0.035	0.11	-10000	0	-0.16	105	105
alphaM/beta2 Integrin/uPAR	0.045	0.082	-10000	0	-0.15	68	68
PLAU	0.026	0.02	-10000	0	0	214	214
PLAT	0.026	0.02	-10000	0	0	213	213
actin filament polymerization	-0.077	0.16	0.2	2	-0.32	135	137
MST1	0.041	0.007	-10000	0	0	15	15
alphaM/beta2 Integrin/lipoprotein(a)	0.065	0.069	-10000	0	-0.1	51	51
TNF	-0.01	0.073	0.26	4	-0.32	9	13
RAP1B	0.038	0.013	-10000	0	0	59	59
alphaM/beta2 Integrin/uPA	0.018	0.094	-10000	0	-0.15	104	104
fibrinolysis	0.039	0.097	-10000	0	-0.14	102	102
HCK	0.036	0.015	-10000	0	0	80	80
dendritic cell antigen processing and presentation	-0.063	0.17	-10000	0	-0.34	123	123
VTN	0.04	0.009	-10000	0	0	24	24
alphaM/beta2 Integrin/CYR61	0.024	0.085	-10000	0	-0.12	112	112
LPA	0.038	0.012	-10000	0	0	55	55
LRP1	0.036	0.014	-10000	0	0	75	75
cell migration	0.019	0.094	0.19	14	-0.13	126	140
FN1	0.021	0.021	-10000	0	0	277	277
alphaM/beta2 Integrin/Thy1	0.007	0.093	-10000	0	-0.12	155	155
MPO	0.041	0.008	-10000	0	0	19	19
KNG1	0.034	0.017	-10000	0	0	109	109
RAP1/GDP	0.039	0.049	-10000	0	-0.12	42	42
ROCK1	-0.083	0.17	0.26	2	-0.34	136	138
ELA2	0.037	0.013	-10000	0	0	64	64
PLG	0.038	0.012	-10000	0	0	49	49
CTGF	0.034	0.017	-10000	0	0	112	112
alphaM/beta2 Integrin/Hck	0.05	0.071	-10000	0	-0.13	49	49
ITGAM	0.042	0.016	-10000	0	-0.054	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.073	0.076	-10000	0	-0.12	54	54
HP	0.01	0.018	-10000	0	0	429	429
leukocyte adhesion	0.019	0.11	-10000	0	-0.22	22	22
SELP	0.039	0.011	-10000	0	0	38	38

×

TCGA08_retinoblastoma

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
CDKN2B	0.029	0.027	-10000	0	-0.046	42	42
CDKN2C	0.029	0.029	-10000	0	-0.043	51	51
CDKN2A	0.022	0.03	-10000	0	-0.039	61	61
CCND2	0.009	0.045	0.11	77	-0.12	2	79
RB1	-0.012	0.066	0.22	7	-0.14	86	93
CDK4	0.01	0.056	0.13	79	-0.12	19	98
CDK6	0.006	0.063	0.14	79	-0.12	43	122
G1/S progression	0.02	0.075	0.14	108	-0.23	8	116

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.021	0.021	-10000	0	0	282	282
positive regulation of NF-kappaB transcription factor activity	0.002	0.067	-10000	0	-0.13	95	95
MAP2K4	-0.013	0.096	0.18	2	-0.27	39	41
IKBKB	0.039	0.011	-10000	0	0	44	44
TNFRSF10B	0.033	0.018	-10000	0	0	126	126
TNFRSF10A	0.031	0.018	-10000	0	0	141	141
SMPD1	-0.008	0.044	-10000	0	-0.1	92	92
IKBKG	0.042	0.003	-10000	0	0	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.032	0.018	-10000	0	0	137	137
TRAIL/TRAILR2	0.002	0.067	-10000	0	-0.13	96	96
TRAIL/TRAILR3	0.001	0.067	-10000	0	-0.13	100	100
TRAIL/TRAILR1	-0.001	0.069	-10000	0	-0.13	101	101
TRAIL/TRAILR4	0.002	0.067	-10000	0	-0.13	95	95
TRAIL/TRAILR1/DAP3/GTP	0.01	0.065	-10000	0	-0.1	99	99
IKK complex	0.02	0.091	-10000	0	-0.32	22	22
RIPK1	0.038	0.012	-10000	0	0	48	48
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.027	0.021	-10000	0	-0.13	9	9
MAPK3	-0.01	0.01	-10000	0	-10000	0	0
MAP3K1	-0.008	0.1	-10000	0	-0.28	39	39
TRAILR4 (trimer)	0.032	0.018	-10000	0	0	137	137
TRADD	0.036	0.014	-10000	0	0	76	76
TRAILR1 (trimer)	0.031	0.018	-10000	0	0	141	141
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.022	0.083	-10000	0	-0.18	95	95
CFLAR	0.04	0.008	-10000	0	0	21	21
MAPK1	-0.01	0.01	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.025	0.082	-10000	0	-0.11	87	87
mol:ceramide	-0.007	0.044	-10000	0	-0.1	92	92
FADD	0.04	0.008	-10000	0	0	21	21
MAPK8	-0.022	0.1	0.2	5	-0.26	50	55
TRAF2	0.04	0.009	-10000	0	0	29	29
TRAILR3 (trimer)	0.032	0.018	-10000	0	0	134	134
CHUK	0.038	0.012	-10000	0	0	52	52
TRAIL/TRAILR1/FADD	0.01	0.07	-10000	0	-0.12	98	98
DAP3	0.039	0.011	-10000	0	0	40	40
CASP10	-0.006	0.1	0.16	82	-0.2	79	161
JNK cascade	0.002	0.067	-10000	0	-0.13	95	95
TRAIL (trimer)	0.021	0.021	-10000	0	0	282	282
TNFRSF10C	0.032	0.018	-10000	0	0	134	134
TRAIL/TRAILR1/DAP3/GTP/FADD	0.021	0.073	-10000	0	-0.11	95	95
TRAIL/TRAILR2/FADD	0.013	0.069	-10000	0	-0.11	94	94
cell death	-0.007	0.044	-10000	0	-0.1	92	92
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.022	0.083	-10000	0	-0.18	92	92
TRAILR2 (trimer)	0.032	0.018	-10000	0	0	126	126
CASP8	-0.001	0.11	-10000	0	-0.65	13	13
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.028	0.082	-10000	0	-0.11	81	81

×

Nongenotropic Androgen 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
PTK2	-0.007	0.005	0	204	-10000	0	204
GNB1/GNG2	0.041	0.07	-10000	0	-0.11	89	89
regulation of S phase of mitotic cell cycle	-0.012	0.076	-10000	0	-0.17	93	93
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.039	0.01	-10000	0	0	31	31
SHBG/T-DHT	0.026	0.007	-10000	0	-10000	0	0
PELP1	0.039	0.01	-10000	0	0	36	36
AKT1	-0.009	0.004	0.002	47	-10000	0	47
MAP2K1	-0.033	0.079	0.17	27	-0.17	78	105
T-DHT/AR	0.006	0.055	-10000	0	-0.13	79	79
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	103	103
GNAI2	0.041	0.007	-10000	0	0	15	15
GNAI3	0.039	0.011	-10000	0	0	45	45
GNAI1	0.035	0.016	-10000	0	0	95	95
mol:GDP	-0.042	0.088	-10000	0	-0.24	82	82
cell proliferation	-0.07	0.17	0.24	6	-0.39	107	113
PIK3CA	0.03	0.019	-10000	0	0	155	155
FOS	-0.12	0.29	0.27	1	-0.7	105	106
mol:Ca2+	-0.006	0.021	-10000	0	-0.048	82	82
MAPK3	-0.052	0.13	0.22	7	-0.3	94	101
MAPK1	-0.042	0.14	-10000	0	-0.34	62	62
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	0	0.002	0.002	77	-0.004	103	180
cAMP biosynthetic process	-0.001	0.024	0.16	6	-10000	0	6
GNG2	0.039	0.01	-10000	0	0	34	34
potassium channel inhibitor activity	0	0.002	0.002	77	-0.004	103	180
HRAS/GTP	0.025	0.078	-10000	0	-0.093	142	142
actin cytoskeleton reorganization	0.029	0.052	-10000	0	-0.11	46	46
SRC	0.039	0.01	-10000	0	0	36	36
voltage-gated calcium channel activity	0	0.002	0.002	77	-0.004	103	180
PI3K	0.023	0.052	-10000	0	-0.12	48	48
apoptosis	0.061	0.18	0.38	114	-0.22	5	119
T-DHT/AR/PELP1	0.025	0.058	-10000	0	-0.11	79	79
HRAS/GDP	-0.006	0.11	0.15	1	-0.23	82	83
CREB1	-0.076	0.18	0.22	5	-0.41	114	119
RAC1-CDC42/GTP	0.038	0.059	-10000	0	-0.11	46	46
AR	0.033	0.017	-10000	0	0	122	122
GNB1	0.041	0.005	-10000	0	0	7	7
RAF1	-0.02	0.076	0.18	29	-0.18	17	46
RAC1-CDC42/GDP	0.016	0.12	0.19	3	-0.23	78	81
T-DHT/AR/PELP1/Src	0.039	0.066	-10000	0	-0.11	78	78
MAP2K2	-0.03	0.074	0.17	22	-0.17	68	90
T-DHT/AR/PELP1/Src/PI3K	-0.012	0.077	-10000	0	-0.17	93	93
GNAZ	0.039	0.011	-10000	0	0	42	42
SHBG	0.039	0.01	-10000	0	0	35	35
Gi family/GNB1/GNG2/GDP	-0.005	0.099	-10000	0	-0.3	34	34
mol:T-DHT	0	0.001	-10000	0	-0.004	27	27
RAC1	0.039	0.01	-10000	0	0	34	34
GNRH1	-0.008	0.004	0	125	-10000	0	125
Gi family/GTP	-0.02	0.077	-10000	0	-0.18	72	72
CDC42	0.04	0.009	-10000	0	0	24	24

×

Thromboxane A2 receptor signaling

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
TGM2	0.033	0.017	-10000	0	0	114	114
GNB1/GNG2	-0.064	0.086	-10000	0	-0.18	190	190
AKT1	-0.027	0.14	0.25	2	-0.23	73	75
EGF	0.038	0.012	-10000	0	0	53	53
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.005	0.06	0.22	8	-0.18	2	10
mol:Ca2+	-0.052	0.19	0.3	2	-0.3	191	193
LYN	0.002	0.057	0.22	9	-0.17	4	13
RhoA/GTP	-0.019	0.088	0.14	5	-0.13	179	184
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.072	0.21	0.32	1	-0.34	191	192
GNG2	0.039	0.01	-10000	0	0	34	34
ARRB2	0.039	0.011	-10000	0	0	44	44
TP alpha/Gq family/GDP/G beta5/gamma2	-0.024	0.16	-10000	0	-0.53	45	45
G beta5/gamma2	-0.073	0.12	-10000	0	-0.24	189	189
PRKCH	-0.072	0.22	0.33	1	-0.35	189	190
DNM1	0.039	0.011	-10000	0	0	38	38
TXA2/TP beta/beta Arrestin3	0.029	0.023	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.041	0.006	-10000	0	0	12	12
G12 family/GTP	-0.066	0.18	-10000	0	-0.3	188	188
ADRBK1	0.041	0.005	-10000	0	0	7	7
ADRBK2	0.036	0.015	-10000	0	0	84	84
RhoA/GTP/ROCK1	0.052	0.022	-10000	0	-0.11	8	8
mol:GDP	0.031	0.16	0.45	44	-0.24	1	45
mol:NADP	0.038	0.012	-10000	0	0	49	49
RAB11A	0.04	0.009	-10000	0	0	24	24
PRKG1	0.04	0.009	-10000	0	0	29	29
mol:IP3	-0.075	0.23	0.35	1	-0.37	193	194
cell morphogenesis	0.051	0.022	-10000	0	-0.11	8	8
PLCB2	-0.12	0.3	-10000	0	-0.5	192	192
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.002	0.053	0.24	6	-0.18	2	8
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.003	0.057	0.2	10	-0.18	3	13
RHOA	0.041	0.007	-10000	0	0	14	14
PTGIR	0.04	0.01	-10000	0	0	32	32
PRKCB1	-0.077	0.23	0.34	1	-0.38	188	189
GNAQ	0.038	0.012	-10000	0	0	49	49
mol:L-citrulline	0.038	0.012	-10000	0	0	49	49
TXA2/TXA2-R family	-0.12	0.3	-10000	0	-0.52	191	191
LCK	0.004	0.058	0.22	8	-0.18	2	10
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.052	0.049	0.23	2	-0.15	8	10
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.1	-10000	0	-0.42	27	27
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.048	0.05	0.23	2	-0.15	8	10
MAPK14	-0.04	0.15	0.24	4	-0.23	181	185
TGM2/GTP	-0.085	0.25	0.4	1	-0.41	170	171
MAPK11	-0.048	0.14	0.25	2	-0.22	188	190
ARHGEF1	-0.029	0.12	0.2	9	-0.18	183	192
GNAI2	0.041	0.007	-10000	0	0	15	15
JNK cascade	-0.077	0.23	0.35	1	-0.38	191	192
RAB11/GDP	0.04	0.009	-10000	0	0	24	24
ICAM1	-0.058	0.2	0.28	5	-0.32	182	187
cAMP biosynthetic process	-0.07	0.21	0.33	1	-0.34	179	180
Gq family/GTP/EBP50	0.01	0.05	0.25	2	-0.15	35	37
actin cytoskeleton reorganization	0.051	0.022	-10000	0	-0.11	8	8
SRC	0.003	0.058	0.22	7	-0.18	2	9
GNB5	0.04	0.009	-10000	0	0	29	29
GNB1	0.041	0.005	-10000	0	0	7	7
EGF/EGFR	0.002	0.075	0.22	11	-0.21	12	23
VCAM1	-0.062	0.21	0.28	4	-0.33	190	194
TP beta/Gq family/GDP/G beta5/gamma2	-0.024	0.16	-10000	0	-0.53	45	45
platelet activation	-0.056	0.19	0.33	1	-0.3	189	190
PGI2/IP	0.028	0.016	-10000	0	-0.13	5	5
PRKACA	0.019	0.023	-10000	0	-0.16	7	7
Gq family/GDP/G beta5/gamma2	-0.015	0.13	-10000	0	-0.46	36	36
TXA2/TP beta/beta Arrestin2	0.013	0.062	-10000	0	-0.3	15	15
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.004	0.024	0.11	6	-0.15	7	13
mol:DAG	-0.089	0.26	0.36	1	-0.42	189	190
EGFR	0.037	0.014	-10000	0	0	72	72
TXA2/TP alpha	-0.1	0.28	0.38	1	-0.46	179	180
Gq family/GTP	-0.008	0.065	-10000	0	-0.19	59	59
YES1	0.002	0.057	0.22	7	-0.18	2	9
GNAI2/GTP	0.027	0.046	-10000	0	-0.13	13	13
PGD2/DP	0.03	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.038	0.012	-10000	0	0	49	49
FYN	0.002	0.058	0.2	10	-0.16	8	18
mol:NO	0.038	0.012	-10000	0	0	49	49
GNA15	0.037	0.014	-10000	0	0	69	69
PGK/cGMP	0.049	0.019	-10000	0	-10000	0	0
RhoA/GDP	0.041	0.007	-10000	0	0	14	14
TP alpha/TGM2/GDP/G beta/gamma	0.06	0.063	0.26	1	-0.17	8	9
NOS3	0.038	0.012	-10000	0	0	49	49
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCA	-0.072	0.22	0.32	3	-0.36	185	188
PRKCB	-0.07	0.22	0.31	1	-0.35	190	191
PRKCE	-0.071	0.22	0.32	5	-0.36	187	192
PRKCD	-0.08	0.23	0.33	1	-0.38	188	189
PRKCG	-0.08	0.24	0.34	1	-0.38	191	192
muscle contraction	-0.11	0.28	0.38	1	-0.48	191	192
PRKCZ	-0.07	0.21	0.3	2	-0.34	191	193
ARR3	0.042	0.002	-10000	0	0	1	1
TXA2/TP beta	0.045	0.052	0.24	1	-0.14	9	10
PRKCQ	-0.072	0.22	0.36	3	-0.36	183	186
MAPKKK cascade	-0.099	0.26	0.36	1	-0.44	188	189
SELE	-0.051	0.18	0.28	3	-0.29	191	194
TP beta/GNAI2/GDP/G beta/gamma	0.071	0.059	0.26	1	-0.16	9	10
ROCK1	0.041	0.007	-10000	0	0	14	14
GNA14	0.039	0.01	-10000	0	0	33	33
chemotaxis	-0.15	0.34	-10000	0	-0.6	191	191
GNA12	0.04	0.01	-10000	0	0	32	32
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	61	61
Rac1/GTP	0.029	0.01	-10000	0	-0.13	1	1

×

BARD1 signaling events

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
BARD1/CSTF1	0.039	0.053	-10000	0	-0.14	38	38
ATM	0.036	0.014	-10000	0	0	73	73
UBE2D3	0.038	0.012	-10000	0	0	48	48
PRKDC	0.039	0.011	-10000	0	0	44	44
ATR	0.035	0.016	-10000	0	0	93	93
UBE2L3	0.039	0.011	-10000	0	0	40	40
FANCD2	-0.004	0.089	-10000	0	-0.25	58	58
protein ubiquitination	0.013	0.1	-10000	0	-0.13	156	156
XRCC5	0.039	0.011	-10000	0	0	39	39
XRCC6	0.037	0.014	-10000	0	0	70	70
M/R/N Complex	0.048	0.071	-10000	0	-0.15	50	50
MRE11A	0.038	0.012	-10000	0	0	54	54
DNA-PK	0.054	0.066	-10000	0	-0.14	46	46
FA complex/FANCD2/Ubiquitin	-0.007	0.13	-10000	0	-0.44	29	29
FANCF	0.04	0.009	-10000	0	0	28	28
BRCA1	0.034	0.016	-10000	0	0	106	106
CCNE1	0.028	0.02	-10000	0	0	189	189
CDK2/Cyclin E1	0.01	0.077	-10000	0	-0.14	104	104
FANCG	0.04	0.008	-10000	0	0	22	22
BRCA1/BACH1/BARD1	0.027	0.069	-10000	0	-0.14	74	74
FANCE	0.041	0.007	-10000	0	0	18	18
FANCC	0.04	0.009	-10000	0	0	29	29
NBN	0.035	0.016	-10000	0	0	96	96
FANCA	0.035	0.016	-10000	0	0	94	94
DNA repair	-0.02	0.13	0.27	13	-0.37	38	51
BRCA1/BARD1/ubiquitin	0.027	0.069	-10000	0	-0.14	74	74
BARD1/DNA-PK	0.064	0.082	-10000	0	-0.14	60	60
FANCL	0.038	0.012	-10000	0	0	55	55
mRNA polyadenylation	-0.038	0.053	0.14	38	-10000	0	38
BRCA1/BARD1/CTIP/M/R/N Complex	-0.025	0.14	0.16	3	-0.29	80	83
BRCA1/BACH1/BARD1/TopBP1	0.037	0.077	-10000	0	-0.13	81	81
BRCA1/BARD1/P53	0.002	0.1	-10000	0	-0.13	190	190
BARD1/CSTF1/BRCA1	0.037	0.072	-10000	0	-0.12	75	75
BRCA1/BACH1	0.034	0.016	-10000	0	0	106	106
BARD1	0.037	0.014	-10000	0	0	66	66
PCNA	0.034	0.016	-10000	0	0	100	100
BRCA1/BARD1/UbcH5C	0.041	0.072	-10000	0	-0.12	75	75
BRCA1/BARD1/UbcH7	0.042	0.072	-10000	0	-0.12	73	73
BRCA1/BARD1/RAD51/PCNA	0.035	0.095	-10000	0	-0.13	115	115
BARD1/DNA-PK/P53	0.019	0.12	-10000	0	-0.13	179	179
BRCA1/BARD1/Ubiquitin	0.027	0.069	-10000	0	-0.14	74	74
BRCA1/BARD1/CTIP	0.014	0.086	0.18	9	-0.13	123	132
FA complex	0.012	0.087	-10000	0	-0.3	26	26
BARD1/EWS	0.042	0.05	-10000	0	-0.13	35	35
RBBP8	-0.015	0.009	-10000	0	-10000	0	0
TP53	0.026	0.02	-10000	0	0	213	213
TOPBP1	0.038	0.013	-10000	0	0	59	59
G1/S transition of mitotic cell cycle	0	0.1	0.13	190	-10000	0	190
BRCA1/BARD1	0.018	0.11	-10000	0	-0.13	150	150
CSTF1	0.037	0.014	-10000	0	0	68	68
BARD1/EWS-Fli1	0.02	0.038	-10000	0	-0.13	34	34
CDK2	0.038	0.013	-10000	0	0	59	59
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.035	0.016	-10000	0	0	93	93
RAD50	0.039	0.011	-10000	0	0	42	42
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.069	-10000	0	-0.14	74	74
EWSR1	0.038	0.012	-10000	0	0	54	54

×

TCGA08_rtk_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
PDGFRA	0.03	0.019	-10000	0	0	157	157
HRAS	0.04	0.01	-10000	0	0	31	31
EGFR	0.037	0.014	-10000	0	0	72	72
AKT	0.017	0.092	0.23	6	-0.18	38	44
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.039	0.01	-10000	0	0	37	37
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.03	0.019	-10000	0	0	155	155
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.027	0.02	-10000	0	0	198	198
PIK3CA	0.03	0.019	-10000	0	0	155	155
PIK3CB	0.034	0.016	-10000	0	0	103	103
NRAS	0.04	0.009	-10000	0	0	30	30
PIK3CG	0.033	0.017	-10000	0	0	118	118
PIK3R3	0.035	0.016	-10000	0	0	97	97
PIK3R2	0.037	0.013	-10000	0	0	63	63
NF1	0.034	0.016	-10000	0	0	101	101
RAS	0.005	0.078	0.15	35	-0.24	20	55
ERBB2	0.038	0.012	-10000	0	0	52	52
proliferation/survival/translation	-0.017	0.086	0.21	32	-0.21	21	53
PI3K	0.003	0.088	0.17	28	-0.21	47	75
PIK3R1	0.034	0.017	-10000	0	0	108	108
KRAS	0.034	0.016	-10000	0	0	103	103
FOXO	0.038	0.054	0.17	24	-10000	0	24
AKT2	0.038	0.012	-10000	0	0	47	47
PTEN	0.039	0.011	-10000	0	0	38	38

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.039	0.011	-10000	0	0	38	38
Rac1/GDP	0.033	0.025	-10000	0	-0.024	66	66
DOCK1	0.037	0.013	-10000	0	0	62	62
ITGA4	0.035	0.015	-10000	0	0	88	88
RAC1	0.039	0.01	-10000	0	0	34	34
alpha4/beta7 Integrin	0.033	0.065	-10000	0	-0.14	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	52	52
alpha4/beta1 Integrin	0.047	0.062	-10000	0	-0.12	49	49
alpha4/beta7 Integrin/Paxillin	0.052	0.069	0.18	55	-0.12	50	105
lamellipodium assembly	-0.03	0.15	-10000	0	-0.36	75	75
PIK3CA	0.03	0.019	-10000	0	0	155	155
PI3K	0.024	0.061	-10000	0	-0.15	47	47
ARF6	0.041	0.008	-10000	0	0	19	19
TLN1	0.039	0.012	-10000	0	0	46	46
PXN	-0.017	0.008	-10000	0	-10000	0	0
PIK3R1	0.034	0.017	-10000	0	0	108	108
ARF6/GTP	0.062	0.071	-10000	0	-0.11	51	51
cell adhesion	0.061	0.077	0.2	47	-0.12	59	106
CRKL/CBL	0.055	0.021	-10000	0	-0.14	1	1
alpha4/beta1 Integrin/Paxillin	0.051	0.067	0.18	51	-0.11	48	99
ITGB1	0.039	0.011	-10000	0	0	38	38
ITGB7	0.039	0.011	-10000	0	0	40	40
ARF6/GDP	0.034	0.025	-10000	0	-0.024	66	66
alpha4/beta1 Integrin/Paxillin/VCAM1	0.025	0.094	0.2	28	-0.13	117	145
p130Cas/Crk/Dock1	0.055	0.054	-10000	0	-0.12	29	29
VCAM1	0.02	0.021	-10000	0	0	288	288
alpha4/beta1 Integrin/Paxillin/Talin	0.063	0.079	0.2	47	-0.12	59	106
alpha4/beta1 Integrin/Paxillin/GIT1	0.069	0.073	0.2	46	-0.11	48	94
BCAR1	0.036	0.014	-10000	0	0	76	76
mol:GDP	-0.066	0.071	0.11	48	-0.2	46	94
CBL	0.04	0.008	-10000	0	0	23	23
PRKACA	0.035	0.015	-10000	0	0	89	89
GIT1	0.04	0.009	-10000	0	0	27	27
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.063	0.079	0.2	47	-0.12	59	106
Rac1/GTP	-0.035	0.17	-10000	0	-0.4	75	75

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.065	0.18	-10000	0	-0.39	123	123
IHH	0.022	0.067	-10000	0	-0.099	128	128
SHH Np/Cholesterol/GAS1	0.027	0.027	-10000	0	-0.1	15	15
LRPAP1	0.036	0.015	-10000	0	0	78	78
dorsoventral neural tube patterning	-0.027	0.027	0.1	15	-10000	0	15
SMO/beta Arrestin2	0.018	0.12	0.24	1	-0.2	99	100
SMO	-0.002	0.11	-10000	0	-0.2	109	109
AKT1	-0.013	0.13	-10000	0	-0.39	36	36
ARRB2	0.039	0.011	-10000	0	0	44	44
BOC	0.036	0.015	-10000	0	0	85	85
ADRBK1	0.041	0.005	-10000	0	0	7	7
heart looping	-0.001	0.11	0.19	3	-0.2	109	112
STIL	0	0.096	0.2	29	-0.17	103	132
DHH N/PTCH2	0.058	0.016	-10000	0	-10000	0	0
DHH N/PTCH1	0.003	0.11	-10000	0	-0.19	127	127
PIK3CA	0.03	0.019	-10000	0	0	155	155
DHH	0.041	0.006	-10000	0	0	13	13
PTHLH	-0.032	0.17	-10000	0	-0.38	106	106
determination of left/right symmetry	-0.001	0.11	0.19	3	-0.2	109	112
PIK3R1	0.034	0.017	-10000	0	0	108	108
skeletal system development	-0.032	0.17	-10000	0	-0.38	106	106
IHH N/Hhip	0.035	0.055	-10000	0	-0.06	120	120
DHH N/Hhip	0.054	0.022	-10000	0	-0.14	1	1
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.001	0.11	0.19	3	-0.2	109	112
pancreas development	0.038	0.013	-10000	0	0	56	56
HHAT	0.04	0.008	-10000	0	0	23	23
PI3K	0.024	0.061	-10000	0	-0.15	47	47
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.037	0.014	-10000	0	0	68	68
somite specification	-0.001	0.11	0.19	3	-0.2	109	112
SHH Np/Cholesterol/PTCH1	-0.006	0.085	-10000	0	-0.17	108	108
SHH Np/Cholesterol/PTCH2	0.032	0.017	-10000	0	-0.1	3	3
SHH Np/Cholesterol/Megalin	0.021	0.027	-10000	0	-0.1	14	14
SHH	-0.018	0.007	-10000	0	-10000	0	0
catabolic process	-0.036	0.096	-10000	0	-0.21	128	128
SMO/Vitamin D3	-0.006	0.1	0.2	19	-0.2	106	125
SHH Np/Cholesterol/Hhip	0.03	0.019	-10000	0	-0.1	4	4
LRP2	0.03	0.019	-10000	0	0	162	162
receptor-mediated endocytosis	0.002	0.1	0.19	21	-0.18	103	124
SHH Np/Cholesterol/BOC	0.025	0.029	-10000	0	-0.11	17	17
SHH Np/Cholesterol/CDO	0.023	0.035	-10000	0	-0.1	31	31
mesenchymal cell differentiation	-0.03	0.019	0.1	4	-10000	0	4
mol:Vitamin D3	-0.012	0.089	0.2	26	-0.17	107	133
IHH N/PTCH2	0.039	0.054	-10000	0	-0.064	3	3
CDON	0.035	0.016	-10000	0	0	93	93
IHH N/PTCH1	-0.02	0.11	-10000	0	-0.21	128	128
Megalin/LRPAP1	0.029	0.053	-10000	0	-0.14	37	37
PTCH2	0.04	0.009	-10000	0	0	27	27
SHH Np/Cholesterol	0.034	0.047	0.2	42	-0.099	3	45
PTCH1	-0.036	0.096	-10000	0	-0.21	128	128
HHIP	0.038	0.013	-10000	0	0	56	56

×

IL1-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
UBC13/UEV1A	0.028	0.019	-10000	0	-0.13	8	8
PRKCZ	0.042	0	-10000	0	-10000	0	0
MAP3K7IP2	0.038	0.013	-10000	0	0	59	59
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.034	0.14	-10000	0	-0.31	88	88
IRAK/TOLLIP	0.04	0.027	0.19	4	-0.1	11	15
IKBKB	0.039	0.011	-10000	0	0	44	44
IKBKG	0.042	0.003	-10000	0	0	2	2
IL1 alpha/IL1R2	0.047	0.039	-10000	0	-0.14	16	16
IL1A	0.04	0.01	-10000	0	0	31	31
IL1B	-0.012	0.01	-10000	0	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0.048	0.077	0.22	2	-0.12	60	62
IL1R2	0.036	0.015	-10000	0	0	85	85
IL1R1	0.031	0.019	-10000	0	0	148	148
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.045	0.14	-10000	0	-0.32	91	91
TOLLIP	0.04	0.009	-10000	0	0	29	29
TICAM2	0.038	0.013	-10000	0	0	58	58
MAP3K3	0.041	0.007	-10000	0	0	17	17
TAK1/TAB1/TAB2	0.062	0.054	-10000	0	-0.14	24	24
IKK complex/ELKS	0.014	0.089	0.26	3	-0.28	25	28
JUN	-0.033	0.062	0.15	27	-0.2	16	43
MAP3K7	0.038	0.012	-10000	0	0	47	47
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.001	0.12	0.22	2	-0.17	138	140
IL1 alpha/IL1R1/IL1RAP/MYD88	0.038	0.086	-10000	0	-0.12	95	95
PIK3R1	0.034	0.017	-10000	0	0	108	108
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.038	0.1	-10000	0	-0.13	104	104
IL1 beta fragment/IL1R1/IL1RAP	-0.012	0.096	0.18	4	-0.15	148	152
NFKB1	0.036	0.015	-10000	0	0	84	84
MAPK8	-0.025	0.057	0.17	24	-0.2	15	39
IRAK1	0.016	0.014	-10000	0	-0.11	6	6
IL1RN/IL1R1	0.022	0.072	-10000	0	-0.14	85	85
IRAK4	0.037	0.014	-10000	0	0	72	72
PRKCI	0.027	0.02	-10000	0	0	197	197
TRAF6	0.04	0.008	-10000	0	0	22	22
PI3K	0.024	0.061	-10000	0	-0.15	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.036	0.15	0.17	2	-0.3	103	105
CHUK	0.038	0.012	-10000	0	0	52	52
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.012	0.096	0.18	4	-0.15	148	152
IL1 beta/IL1R2	-0.004	0.089	0.24	2	-0.15	133	135
IRAK/TRAF6/TAK1/TAB1/TAB2	0.072	0.068	0.22	1	-0.14	33	34
NF kappa B1 p50/RelA	-0.015	0.11	-10000	0	-0.18	124	124
IRAK3	0.035	0.016	-10000	0	0	97	97
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.003	0.12	0.22	2	-0.16	145	147
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.099	-10000	0	-0.2	104	104
IL1 alpha/IL1R1/IL1RAP	0.016	0.078	-10000	0	-0.13	95	95
RELA	0.041	0.006	-10000	0	0	10	10
MAP3K7IP1	0.038	0.012	-10000	0	0	54	54
SQSTM1	0.038	0.012	-10000	0	0	49	49
MYD88	0.041	0.007	-10000	0	0	14	14
IRAK/TRAF6/MEKK3	0.061	0.037	0.2	4	-0.11	17	21
IL1RAP	0.027	0.02	-10000	0	0	196	196
UBE2N	0.04	0.008	-10000	0	0	20	20
IRAK/TRAF6	-0.022	0.096	-10000	0	-0.17	136	136
CASP1	0.028	0.02	-10000	0	0	192	192
IL1RN/IL1R2	0.041	0.049	-10000	0	-0.14	31	31
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.002	0.1	0.2	4	-0.15	141	145
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.021	0.13	0.21	1	-0.29	88	89
PIK3CA	0.03	0.019	-10000	0	0	155	155
IL1RN	0.039	0.011	-10000	0	0	39	39
TRAF6/TAK1/TAB1/TAB2	0.073	0.066	-10000	0	-0.14	29	29
MAP2K6	-0.021	0.059	0.19	24	-0.21	13	37

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.029	0.013	-10000	0	-0.13	3	3
alphaV beta3 Integrin	0.028	0.079	-10000	0	-0.13	91	91
PTK2	-0.011	0.13	0.23	9	-0.27	73	82
IGF1R	0.033	0.017	-10000	0	0	118	118
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.031	0.018	-10000	0	0	142	142
SRC	0.039	0.01	-10000	0	0	36	36
CDKN1B	0.002	0.089	-10000	0	-0.32	34	34
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.015	0.059	-10000	0	-0.27	15	15
ROCK1	0.041	0.007	-10000	0	0	14	14
AKT1	0.006	0.055	0.21	5	-0.26	14	19
PTK2B	-0.014	0.06	0.19	13	-0.18	11	24
alphaV/beta3 Integrin/JAM-A	0.041	0.081	0.2	10	-0.12	87	97
CBL	0.04	0.008	-10000	0	0	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.03	0.079	-10000	0	-0.13	91	91
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.056	0.085	-10000	0	-0.12	88	88
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.005	0.084	-10000	0	-0.26	32	32
alphaV/beta3 Integrin/Syndecan-1	0.029	0.079	-10000	0	-0.13	92	92
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.019	0.1	-10000	0	-0.14	173	173
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.03	0.019	-10000	0	0	155	155
alphaV/beta3 Integrin/Osteopontin	0.005	0.099	-10000	0	-0.15	128	128
RPS6KB1	-0.034	0.1	0.28	10	-0.26	16	26
TLN1	0.039	0.012	-10000	0	0	46	46
MAPK3	-0.052	0.16	0.23	1	-0.33	122	123
GPR124	0.037	0.013	-10000	0	0	63	63
MAPK1	-0.049	0.16	0.23	1	-0.34	115	116
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.017	-10000	0	0	108	108
alphaV/beta3 Integrin/Tumstatin	0.031	0.08	-10000	0	-0.13	92	92
cell adhesion	-0.001	0.1	-10000	0	-0.16	136	136
ANGPTL3	0.04	0.008	-10000	0	0	21	21
VEGFR2 homodimer/VEGFA homodimer/Src	0.05	0.02	-10000	0	-0.11	2	2
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	118	118
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
TGFBR2	0.039	0.01	-10000	0	0	37	37
ITGB3	0.033	0.017	-10000	0	0	121	121
IGF1	0.036	0.015	-10000	0	0	84	84
RAC1	0.039	0.01	-10000	0	0	34	34
regulation of cell-matrix adhesion	0.029	0.076	-10000	0	-0.13	83	83
apoptosis	0.033	0.017	-10000	0	0	117	117
CD47	0.037	0.013	-10000	0	0	62	62
alphaV/beta3 Integrin/CD47	0.023	0.087	-10000	0	-0.14	103	103
VCL	0.039	0.01	-10000	0	0	36	36
alphaV/beta3 Integrin/Del1	0.005	0.082	-10000	0	-0.14	111	111
CSF1	0.035	0.015	-10000	0	0	89	89
PIK3C2A	-0.005	0.1	-10000	0	-0.33	47	47
PI4 Kinase/Pyk2	0.006	0.055	-10000	0	-0.11	81	81
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.074	-10000	0	-0.12	94	94
FAK1/Vinculin	0.006	0.12	0.23	10	-0.22	79	89
alphaV beta3/Integrin/ppsTEM5	0.029	0.076	-10000	0	-0.13	83	83
RHOA	0.041	0.007	-10000	0	0	14	14
VTN	0.04	0.009	-10000	0	0	24	24
BCAR1	0.036	0.014	-10000	0	0	76	76
FGF2	0.039	0.011	-10000	0	0	45	45
F11R	-0.018	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.008	0.088	-10000	0	-0.14	125	125
alphaV/beta3 Integrin/TGFBR2	0.027	0.084	-10000	0	-0.14	95	95
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.046	0.091	-10000	0	-0.13	96	96
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.026	0.077	-10000	0	-0.12	100	100
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.021	0.021	-10000	0	0	277	277
alphaV/beta3 Integrin/Pyk2	0.017	0.066	0.21	1	-0.11	87	88
SDC1	0.04	0.009	-10000	0	0	29	29
VAV3	-0.03	0.075	0.2	20	-0.21	38	58
PTPN11	0.04	0.009	-10000	0	0	27	27
IRS1	0.04	0.008	-10000	0	0	22	22
FAK1/Paxillin	0.009	0.12	0.23	9	-0.23	70	79
cell migration	-0.002	0.11	0.21	9	-0.21	78	87
ITGAV	0.033	0.017	-10000	0	0	117	117
PI3K	0.028	0.091	-10000	0	-0.15	73	73
SPP1	0.03	0.019	-10000	0	0	154	154
KDR	0.04	0.009	-10000	0	0	30	30
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.033	0.017	-10000	0	0	117	117
COL4A3	0.041	0.005	-10000	0	0	7	7
angiogenesis	-0.057	0.17	0.25	2	-0.37	118	120
Rac1/GTP	-0.032	0.078	0.2	20	-0.2	38	58
EDIL3	0.027	0.02	-10000	0	0	202	202
cell proliferation	0.026	0.084	-10000	0	-0.14	95	95

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	0.015	0.15	-10000	0	-0.35	32	32
MAP3K8	0.04	0.009	-10000	0	0	21	21
FOS	0.014	0.11	-10000	0	-0.32	22	22
PRKCA	0.026	0.029	-10000	0	-0.015	169	169
PTPN7	0.031	0.032	-10000	0	-0.031	112	112
HRAS	0.039	0.01	-10000	0	0	31	31
PRKCB	0	0.007	0.01	94	-0.013	103	197
NRAS	0.04	0.01	-10000	0	0	30	30
RAS family/GTP	0.054	0.051	-10000	0	-0.11	29	29
MAPK3	0.03	0.081	-10000	0	-0.44	9	9
MAP2K1	0.001	0.096	0.16	3	-0.28	43	46
ELK1	0.028	0.032	-10000	0	-0.038	104	104
BRAF	0.001	0.072	-10000	0	-0.29	27	27
mol:GTP	0	0.002	0.002	86	-0.004	103	189
MAPK1	0.011	0.11	-10000	0	-0.38	33	33
RAF1	-0.002	0.078	-10000	0	-0.28	35	35
KRAS	0.034	0.016	-10000	0	0	103	103

×

IL6-mediated signaling events

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
BCL2L1	-0.089	0.35	-10000	0	-0.8	82	82
CRP	-0.082	0.33	-10000	0	-0.79	73	73
cell cycle arrest	-0.12	0.39	-10000	0	-0.89	90	90
TIMP1	-0.1	0.36	-10000	0	-0.76	112	112
IL6ST	0.024	0.036	-10000	0	-0.042	73	73
Rac1/GDP	-0.011	0.17	0.28	6	-0.36	68	74
AP1	-0.029	0.21	-10000	0	-0.47	78	78
GAB2	0.033	0.02	-10000	0	-0.001	143	143
TNFSF11	-0.087	0.33	-10000	0	-0.78	77	77
HSP90B1	0.013	0.091	-10000	0	-1.1	2	2
GAB1	0.039	0.014	-10000	0	-0.002	55	55
MAPK14	-0.024	0.16	0.25	2	-0.5	39	41
AKT1	-0.01	0.15	0.31	4	-0.42	41	45
FOXO1	-0.011	0.14	0.3	4	-0.4	40	44
MAP2K6	-0.02	0.15	0.22	4	-0.37	57	61
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.032	0.21	0.3	8	-0.42	86	94
MITF	-0.017	0.14	0.22	7	-0.32	68	75
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.037	0.014	-10000	0	0	66	66
A2M	-0.12	0.4	-10000	0	-1.2	66	66
CEBPB	0.037	0.015	-10000	0	0	79	79
GRB2/SOS1/GAB family/SHP2	-0.01	0.16	0.29	4	-0.38	67	71
STAT3	-0.14	0.43	-10000	0	-0.99	90	90
STAT1	-0.069	0.28	-10000	0	-0.83	64	64
CEBPD	-0.086	0.34	0.53	2	-0.8	78	80
PIK3CA	0.031	0.02	-10000	0	-0.001	158	158
PI3K	0.024	0.062	-10000	0	-0.15	49	49
JUN	0.036	0.015	-10000	0	0	80	80
PIAS3/MITF	-0.006	0.15	0.24	4	-0.33	63	67
MAPK11	-0.023	0.16	0.25	2	-0.53	35	37
STAT3 (dimer)/FOXO1	-0.096	0.36	0.47	3	-0.74	103	106
GRB2/SOS1/GAB family	0.031	0.13	0.29	4	-0.27	36	40
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.008	0.11	0.2	3	-0.25	56	59
GRB2	0.042	0.01	-10000	0	-0.005	20	20
JAK2	0.035	0.016	-10000	0	0	92	92
LBP	-0.031	0.27	0.44	1	-0.58	70	71
PIK3R1	0.034	0.018	-10000	0	-0.001	111	111
JAK1	0.034	0.028	-10000	0	-0.044	55	55
MYC	-0.071	0.42	0.52	6	-0.88	99	105
FGG	-0.086	0.33	-10000	0	-0.78	78	78
macrophage differentiation	-0.12	0.39	-10000	0	-0.89	90	90
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.049	0.1	-10000	0	-0.17	49	49
JUNB	-0.1	0.39	0.52	3	-0.86	96	99
FOS	0.026	0.02	-10000	0	0	207	207
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.009	0.16	0.23	5	-0.34	70	75
STAT1/PIAS1	-0.019	0.18	0.29	2	-0.38	74	76
GRB2/SOS1/GAB family/SHP2/PI3K	-0.011	0.16	-10000	0	-0.4	49	49
STAT3 (dimer)	-0.14	0.41	-10000	0	-0.96	90	90
PRKCD	-0.06	0.26	0.34	4	-0.55	92	96
IL6R	0.032	0.027	-10000	0	-0.043	46	46
SOCS3	-0.035	0.21	0.34	1	-0.97	22	23
gp130 (dimer)/JAK1/JAK1/LMO4	0.044	0.089	-10000	0	-0.14	65	65
Rac1/GTP	-0.017	0.18	0.29	6	-0.38	75	81
HCK	0.036	0.015	-10000	0	0	80	80
MAPKKK cascade	-0.024	0.22	-10000	0	-0.5	80	80
bone resorption	-0.079	0.31	-10000	0	-0.73	78	78
IRF1	-0.14	0.42	-10000	0	-0.93	111	111
mol:GDP	-0.02	0.15	0.24	6	-0.35	66	72
SOS1	0.039	0.015	-10000	0	-0.002	59	59
VAV1	-0.021	0.15	0.23	5	-0.35	67	72
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.012	0.17	-10000	0	-0.44	58	58
PTPN11	0	0.16	-10000	0	-0.78	22	22
IL6/IL6RA	0.029	0.063	-10000	0	-0.14	42	42
gp130 (dimer)/TYK2/TYK2/LMO4	0.05	0.066	-10000	0	-0.1	60	60
gp130 (dimer)/JAK2/JAK2/LMO4	0.043	0.075	-10000	0	-0.12	66	66
IL6	0.023	0.037	-10000	0	-0.043	74	74
PIAS3	0.04	0.008	-10000	0	0	23	23
PTPRE	0.027	0.038	0.1	9	-0.047	43	52
PIAS1	0.04	0.009	-10000	0	0	28	28
RAC1	0.04	0.01	-10000	0	0	34	34
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.004	0.095	0.16	2	-0.24	48	50
LMO4	0.028	0.037	-10000	0	-0.043	81	81
STAT3 (dimer)/PIAS3	-0.1	0.4	-10000	0	-0.9	89	89
MCL1	-0.012	0.16	0.36	1	-0.6	22	23

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.056	0.21	-10000	0	-0.36	144	144
Syndecan-4/Syndesmos	-0.037	0.19	-10000	0	-0.42	77	77
positive regulation of JNK cascade	-0.057	0.19	-10000	0	-0.41	84	84
Syndecan-4/ADAM12	-0.054	0.18	-10000	0	-0.46	61	61
CCL5	0.03	0.019	-10000	0	0	161	161
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
DNM2	0.037	0.014	-10000	0	0	72	72
ITGA5	0.038	0.013	-10000	0	0	58	58
SDCBP	0.036	0.014	-10000	0	0	75	75
PLG	0.031	0.03	0.079	4	-0.042	62	66
ADAM12	0.03	0.019	-10000	0	0	163	163
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.04	0.01	-10000	0	0	32	32
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.023	0.023	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.04	0.19	-10000	0	-0.41	77	77
Syndecan-4/CXCL12/CXCR4	-0.06	0.2	-10000	0	-0.44	83	83
Syndecan-4/Laminin alpha3	-0.047	0.19	-10000	0	-0.43	76	76
MDK	0.04	0.009	-10000	0	0	24	24
Syndecan-4/FZD7	-0.041	0.19	-10000	0	-0.46	64	64
Syndecan-4/Midkine	-0.039	0.2	-10000	0	-0.47	59	59
FZD7	0.037	0.013	-10000	0	0	65	65
Syndecan-4/FGFR1/FGF	-0.025	0.18	-10000	0	-0.41	63	63
THBS1	0.027	0.02	-10000	0	0	199	199
integrin-mediated signaling pathway	-0.055	0.18	-10000	0	-0.42	80	80
positive regulation of MAPKKK cascade	-0.057	0.19	-10000	0	-0.41	84	84
Syndecan-4/TACI	-0.037	0.19	-10000	0	-0.43	76	76
CXCR4	0.033	0.017	-10000	0	0	117	117
cell adhesion	-0.032	0.097	0.22	4	-0.2	127	131
Syndecan-4/Dynamin	-0.035	0.19	-10000	0	-0.42	70	70
Syndecan-4/TSP1	-0.058	0.19	-10000	0	-0.46	68	68
Syndecan-4/GIPC	-0.037	0.18	-10000	0	-0.47	51	51
Syndecan-4/RANTES	-0.05	0.2	-10000	0	-0.47	66	66
ITGB1	0.039	0.011	-10000	0	0	38	38
LAMA1	0.034	0.017	-10000	0	0	108	108
LAMA3	0.031	0.018	-10000	0	0	147	147
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCA	0.002	0.12	0.87	8	-10000	0	8
Syndecan-4/alpha-Actinin	-0.039	0.2	-10000	0	-0.43	76	76
TFPI	0.039	0.01	-10000	0	0	35	35
F2	0.038	0.026	0.085	2	-0.038	48	50
alpha5/beta1 Integrin	0.046	0.045	-10000	0	-0.14	27	27
positive regulation of cell adhesion	-0.056	0.17	-10000	0	-0.41	76	76
ACTN1	0.039	0.011	-10000	0	0	42	42
TNC	0.027	0.02	-10000	0	0	198	198
Syndecan-4/CXCL12	-0.057	0.2	-10000	0	-0.44	81	81
FGF6	0.036	0.014	-10000	0	0	73	73
RHOA	0.041	0.007	-10000	0	0	14	14
CXCL12	0.029	0.019	-10000	0	0	172	172
TNFRSF13B	0.039	0.011	-10000	0	0	42	42
FGF2	0.039	0.011	-10000	0	0	45	45
FGFR1	0.033	0.017	-10000	0	0	122	122
Syndecan-4/PI-4-5-P2	-0.06	0.18	-10000	0	-0.46	59	59
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.017	0.025	-10000	0	-0.039	28	28
cell migration	-0.011	0.013	-10000	0	-10000	0	0
PRKCD	0.033	0.028	-10000	0	-0.041	51	51
vasculogenesis	-0.056	0.18	-10000	0	-0.42	76	76
SDC4	-0.052	0.18	-10000	0	-0.5	53	53
Syndecan-4/Tenascin C	-0.058	0.19	-10000	0	-0.46	68	68
Syndecan-4/PI-4-5-P2/PKC alpha	-0.019	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.039	0.19	-10000	0	-0.48	54	54
MMP9	0.027	0.024	-10000	0	-0.04	17	17
Rac1/GTP	-0.033	0.099	0.22	4	-0.2	127	131
cytoskeleton organization	-0.035	0.18	-10000	0	-0.4	77	77
GIPC1	0.035	0.015	-10000	0	0	89	89
Syndecan-4/TFPI	-0.04	0.19	-10000	0	-0.42	77	77

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.037	0.013	-10000	0	0	62	62
LAT2	-0.018	0.1	0.19	3	-0.21	92	95
AP1	-0.031	0.18	-10000	0	-0.42	67	67
mol:PIP3	-0.032	0.13	0.26	13	-0.29	83	96
IKBKB	-0.013	0.088	0.2	24	-0.19	63	87
AKT1	0.015	0.12	0.25	63	-0.22	11	74
IKBKG	-0.02	0.084	0.19	12	-0.19	67	79
MS4A2	0.046	0.012	0.07	38	-0.004	10	48
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.03	0.019	-10000	0	0	155	155
MAP3K1	-0.033	0.13	0.22	3	-0.31	68	71
mol:Ca2+	-0.022	0.11	0.23	14	-0.23	80	94
LYN	0.036	0.019	0.091	2	-0.003	92	94
CBLB	-0.014	0.095	0.2	5	-0.21	77	82
SHC1	0.04	0.01	-10000	0	0	31	31
RasGAP/p62DOK	0.021	0.073	-10000	0	-0.11	107	107
positive regulation of cell migration	-0.01	0.002	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.01	0.081	0.3	21	-0.16	5	26
PTPN13	-0.055	0.2	-10000	0	-0.66	35	35
PTPN11	0.04	0.02	0.11	2	-0.033	23	25
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.006	0.13	0.31	21	-0.33	29	50
SYK	0.037	0.017	0.091	2	-0.003	77	79
GRB2	0.041	0.007	-10000	0	0	17	17
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.023	0.13	0.18	1	-0.27	99	100
LAT	-0.017	0.095	-10000	0	-0.21	83	83
PAK2	-0.031	0.14	0.21	6	-0.32	74	80
NFATC2	0.004	0.054	-10000	0	-0.4	9	9
HRAS	-0.027	0.14	0.22	5	-0.31	84	89
GAB2	0.031	0.018	-10000	0	0	141	141
PLA2G1B	0.01	0.15	-10000	0	-0.88	14	14
Fc epsilon R1	0.034	0.071	-10000	0	-0.094	112	112
Antigen/IgE/Fc epsilon R1	0.037	0.063	-10000	0	-0.081	102	102
mol:GDP	-0.024	0.16	0.26	3	-0.38	66	69
JUN	0.036	0.015	-10000	0	0	80	80
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.034	0.017	-10000	0	0	108	108
FOS	0.026	0.02	-10000	0	0	207	207
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.009	0.1	0.14	5	-0.21	87	92
CHUK	-0.021	0.085	0.2	10	-0.19	75	85
KLRG1	-0.015	0.079	0.16	5	-0.16	91	96
VAV1	-0.015	0.096	0.15	7	-0.22	77	84
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.017	0.097	0.2	3	-0.21	87	90
negative regulation of mast cell degranulation	-0.02	0.073	0.13	1	-0.19	54	55
BTK	-0.03	0.18	0.26	1	-0.51	50	51
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.026	0.11	-10000	0	-0.2	123	123
GAB2/PI3K/SHP2	-0.039	0.055	-10000	0	-0.15	74	74
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.003	0.069	-10000	0	-0.15	86	86
RAF1	0.013	0.16	-10000	0	-0.97	14	14
Fc epsilon R1/FcgammaRIIB/SHIP	0.033	0.092	-10000	0	-0.12	124	124
FCER1G	0.027	0.02	0.066	1	0	201	202
FCER1A	0.039	0.015	0.1	1	-0.005	48	49
Antigen/IgE/Fc epsilon R1/Fyn	0.04	0.077	-10000	0	-0.094	104	104
MAPK3	0.011	0.15	-10000	0	-0.89	14	14
MAPK1	0.004	0.15	-10000	0	-0.9	14	14
NFKB1	0.036	0.015	-10000	0	0	84	84
MAPK8	-0.033	0.22	-10000	0	-0.59	52	52
DUSP1	0.027	0.02	-10000	0	0	206	206
NF-kappa-B/RelA	0.001	0.068	0.14	16	-0.14	66	82
actin cytoskeleton reorganization	-0.049	0.2	-10000	0	-0.73	29	29
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.017	0.13	0.26	3	-0.28	78	81
FER	-0.015	0.094	-10000	0	-0.21	79	79
RELA	0.041	0.006	-10000	0	0	10	10
ITK	-0.002	0.058	-10000	0	-0.28	17	17
SOS1	0.038	0.013	-10000	0	0	56	56
PLCG1	-0.026	0.15	0.24	6	-0.34	80	86
cytokine secretion	-0.003	0.047	0.084	9	-0.098	70	79
SPHK1	-0.017	0.097	0.21	2	-0.21	88	90
PTK2	-0.052	0.21	-10000	0	-0.78	29	29
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.017	0.14	-10000	0	-0.27	106	106
EDG1	-0.01	0.002	-10000	0	-10000	0	0
mol:DAG	-0.033	0.14	0.26	12	-0.3	84	96
MAP2K2	0.003	0.15	-10000	0	-0.9	14	14
MAP2K1	0.004	0.15	-10000	0	-0.91	14	14
MAP2K7	0.039	0.011	-10000	0	0	43	43
KLRG1/SHP2	0.013	0.091	0.2	37	-0.18	55	92
MAP2K4	-0.072	0.32	-10000	0	-0.89	75	75
Fc epsilon R1/FcgammaRIIB	0.035	0.1	-10000	0	-0.13	124	124
mol:Choline	-0.01	0.081	0.3	21	-0.16	5	26
SHC/Grb2/SOS1	0.023	0.13	-10000	0	-0.21	88	88
FYN	0.034	0.016	-10000	0	0	103	103
DOK1	0.04	0.009	-10000	0	0	24	24
PXN	-0.052	0.19	-10000	0	-0.71	29	29
HCLS1	-0.01	0.099	0.19	7	-0.24	62	69
PRKCB	-0.024	0.11	0.22	14	-0.23	84	98
FCGR2B	0.03	0.019	-10000	0	0	164	164
IGHE	0	0.007	0.048	2	-10000	0	2
KLRG1/SHIP	-0.02	0.075	0.13	1	-0.19	54	55
LCP2	0.034	0.016	-10000	0	0	102	102
PLA2G4A	-0.007	0.092	0.17	11	-0.22	65	76
RASA1	0.037	0.014	-10000	0	0	71	71
mol:Phosphatidic acid	-0.01	0.081	0.3	21	-0.16	5	26
IKK complex	-0.015	0.073	0.18	19	-0.16	51	70
WIPF1	0	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.16	0.61	-10000	0	-1.2	120	120
IL23A	-0.11	0.55	-10000	0	-1.2	86	86
NF kappa B1 p50/RelA/I kappa B alpha	-0.11	0.55	-10000	0	-1.1	100	100
positive regulation of T cell mediated cytotoxicity	-0.13	0.61	0.68	1	-1.3	91	92
ITGA3	-0.16	0.58	-10000	0	-1.1	121	121
IL17F	-0.042	0.36	0.5	11	-0.69	95	106
IL12B	0.034	0.074	0.16	11	-0.078	23	34
STAT1 (dimer)	-0.15	0.58	-10000	0	-1.3	89	89
CD4	-0.11	0.57	0.72	2	-1.2	98	100
IL23	-0.1	0.53	-10000	0	-1.2	82	82
IL23R	0.039	0.14	-10000	0	-1.2	3	3
IL1B	-0.13	0.59	-10000	0	-1.3	95	95
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.095	0.52	-10000	0	-1.1	85	85
TYK2	0.025	0.056	0.13	1	-10000	0	1
STAT4	0.04	0.009	-10000	0	0	29	29
STAT3	0.038	0.013	-10000	0	0	56	56
IL18RAP	0.042	0.007	-10000	0	-10000	0	0
IL12RB1	0.024	0.057	0.13	1	-0.066	2	3
PIK3CA	0.03	0.019	-10000	0	0	155	155
IL12Rbeta1/TYK2	0.037	0.069	-10000	0	-10000	0	0
IL23R/JAK2	0.051	0.18	-10000	0	-1.2	3	3
positive regulation of chronic inflammatory response	-0.13	0.61	0.68	1	-1.3	91	92
natural killer cell activation	-0.002	0.01	-10000	0	-10000	0	0
JAK2	0.032	0.07	0.16	11	-0.078	20	31
PIK3R1	0.034	0.017	-10000	0	0	108	108
NFKB1	0.037	0.016	-10000	0	0	84	84
RELA	0.043	0.008	-10000	0	0	10	10
positive regulation of dendritic cell antigen processing and presentation	-0.091	0.5	-10000	0	-1.1	82	82
ALOX12B	-0.098	0.52	-10000	0	-1.1	84	84
CXCL1	-0.13	0.57	-10000	0	-1.2	110	110
T cell proliferation	-0.13	0.61	0.68	1	-1.3	91	92
NFKBIA	0.039	0.015	-10000	0	0	66	66
IL17A	-0.03	0.29	0.43	10	-0.54	93	103
PI3K	-0.15	0.53	-10000	0	-1.2	89	89
IFNG	0.007	0.04	0.1	5	-0.11	14	19
STAT3 (dimer)	-0.13	0.51	-10000	0	-1.1	88	88
IL18R1	0.041	0.008	-10000	0	-10000	0	0
IL23/IL23R/JAK2/TYK2/SOCS3	-0.013	0.34	0.54	3	-0.65	76	79
IL18/IL18R	0.055	0.067	-10000	0	-0.11	62	62
macrophage activation	-0.007	0.022	0.034	2	-0.045	80	82
TNF	-0.11	0.55	-10000	0	-1.2	85	85
STAT3/STAT4	-0.12	0.56	-10000	0	-1.2	89	89
STAT4 (dimer)	-0.13	0.58	-10000	0	-1.3	89	89
IL18	0.032	0.019	-10000	0	-10000	0	0
IL19	-0.095	0.52	-10000	0	-1.1	86	86
STAT5A (dimer)	-0.13	0.58	-10000	0	-1.3	90	90
STAT1	0.034	0.017	-10000	0	0	108	108
SOCS3	0.037	0.014	-10000	0	0	67	67
CXCL9	-0.16	0.61	-10000	0	-1.2	124	124
MPO	-0.096	0.52	-10000	0	-1.1	85	85
positive regulation of humoral immune response	-0.13	0.61	0.68	1	-1.3	91	92
IL23/IL23R/JAK2/TYK2	-0.16	0.66	-10000	0	-1.5	90	90
IL6	-0.1	0.54	-10000	0	-1.2	90	90
STAT5A	0.038	0.012	-10000	0	0	51	51
IL2	0.039	0.017	-10000	0	-0.033	11	11
positive regulation of tyrosine phosphorylation of STAT protein	-0.002	0.01	-10000	0	-10000	0	0
CD3E	-0.11	0.54	-10000	0	-1.2	87	87
keratinocyte proliferation	-0.13	0.61	0.68	1	-1.3	91	92
NOS2	-0.098	0.52	-10000	0	-1.1	92	92

×

Signaling events mediated by PRL

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
CCNE1	0.028	0.02	-10000	0	0	189	189
mol:Halofuginone	0.002	0.022	-10000	0	-0.17	9	9
ITGA1	0.033	0.017	-10000	0	0	124	124
CDKN1A	0.02	0.08	-10000	0	-0.36	18	18
PRL-3/alpha Tubulin	0.01	0.039	-10000	0	-0.13	36	36
mol:Ca2+	-0.003	0.071	0.26	35	-10000	0	35
AGT	0.039	0.011	-10000	0	0	44	44
CCNA2	-0.016	0.088	-10000	0	-0.62	7	7
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	0.007	0.043	-10000	0	-0.32	9	9
CDK2/Cyclin E1	0.025	0.097	-10000	0	-0.34	21	21
MAPK3	-0.012	0.01	0	236	-10000	0	236
PRL-2 /Rab GGTase beta	0.032	0.068	-10000	0	-0.14	72	72
MAPK1	-0.012	0.01	0	251	-10000	0	251
PTP4A1	-0.003	0.075	0.2	4	-0.61	7	11
PTP4A3	0.025	0.021	-10000	0	0	226	226
PTP4A2	0.04	0.01	-10000	0	0	31	31
ITGB1	-0.012	0.01	0	251	-10000	0	251
SRC	0.039	0.01	-10000	0	0	36	36
RAC1	-0.008	0.11	-10000	0	-0.36	45	45
Rab GGTase beta/Rab GGTase alpha	0.035	0.063	-10000	0	-0.14	63	63
PRL-1/ATF-5	0.016	0.097	0.3	3	-0.54	9	12
RABGGTA	0.04	0.009	-10000	0	0	26	26
BCAR1	-0.003	0.068	0.26	32	-10000	0	32
RHOC	-0.005	0.11	-10000	0	-0.36	42	42
RHOA	-0.008	0.11	-10000	0	-0.36	46	46
cell motility	0.011	0.12	0.3	2	-0.34	44	46
PRL-1/alpha Tubulin	-0.018	0.078	-10000	0	-0.54	9	9
PRL-3/alpha1 Integrin	0.011	0.067	-10000	0	-0.15	67	67
ROCK1	0.011	0.12	0.3	2	-0.34	44	46
RABGGTB	0.036	0.015	-10000	0	0	84	84
CDK2	0.038	0.013	-10000	0	0	59	59
mitosis	-0.002	0.076	0.2	6	-0.61	7	13
ATF5	0.038	0.012	-10000	0	0	54	54

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.033	0.017	-10000	0	0	120	120
ANTXR2	0.035	0.015	-10000	0	0	91	91
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.006	0.011	-10000	0	-0.033	74	74
monocyte activation	-0.076	0.17	-10000	0	-0.35	151	151
MAP2K2	-0.039	0.18	-10000	0	-0.58	56	56
MAP2K1	-0.011	0.011	0.007	39	-0.037	69	108
MAP2K7	-0.01	0.011	0.007	38	-0.037	68	106
MAP2K6	-0.009	0.012	0.007	34	-0.038	61	95
CYAA	-0.022	0.032	-10000	0	-0.1	73	73
MAP2K4	-0.01	0.012	0.007	33	-0.038	68	101
IL1B	-0.012	0.041	0.1	9	-0.09	82	91
Channel	0.023	0.056	-10000	0	-0.11	74	74
NLRP1	-0.006	0.01	-10000	0	-0.03	74	74
CALM1	0.04	0.01	-10000	0	0	31	31
negative regulation of phagocytosis	0.003	0.078	-10000	0	-0.42	17	17
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.006	0.011	0.033	74	-10000	0	74
MAPK3	-0.011	0.011	0.007	38	-0.037	72	110
MAPK1	-0.01	0.011	0.007	37	-0.037	66	103
PGR	-0.008	0.011	0.007	36	-0.037	51	87
PA/Cellular Receptors	0.023	0.061	-10000	0	-0.12	73	73
apoptosis	-0.006	0.011	-10000	0	-0.033	74	74
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.022	0.055	-10000	0	-0.11	74	74
macrophage activation	-0.012	0.021	0.17	3	-0.11	1	4
TNF	0.04	0.009	-10000	0	0	26	26
VCAM1	-0.078	0.17	-10000	0	-0.35	149	149
platelet activation	0.003	0.078	-10000	0	-0.42	17	17
MAPKKK cascade	0.007	0.028	0.083	8	-0.087	6	14
IL18	-0.009	0.041	0.093	8	-0.093	73	81
negative regulation of macrophage activation	-0.006	0.011	-10000	0	-0.033	74	74
LEF	-0.006	0.011	-10000	0	-0.033	74	74
CASP1	0	0.012	0.018	34	-0.031	49	83
mol:cAMP	0	0.077	-10000	0	-0.43	17	17
necrosis	-0.006	0.011	-10000	0	-0.033	74	74
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.023	0.053	-10000	0	-0.1	74	74
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.011	0.076	-10000	0	-0.14	104	104
CRKL	-0.032	0.14	0.33	1	-0.43	43	44
mol:PIP3	0.007	0.079	-10000	0	-0.83	4	4
AKT1	0.001	0.081	0.38	2	-0.73	4	6
PTK2B	0.033	0.017	-10000	0	0	118	118
RAPGEF1	-0.034	0.14	0.31	1	-0.41	42	43
RANBP10	0.036	0.014	-10000	0	0	77	77
PIK3CA	0.03	0.019	-10000	0	0	155	155
HGF/MET/SHIP2	0.029	0.078	-10000	0	-0.12	102	102
MAP3K5	-0.024	0.14	0.28	2	-0.4	46	48
HGF/MET/CIN85/CBL/ENDOPHILINS	0.051	0.085	-10000	0	-0.11	105	105
AP1	-0.004	0.082	0.15	12	-0.14	106	118
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.04	0.01	-10000	0	0	31	31
apoptosis	-0.16	0.36	-10000	0	-0.77	138	138
STAT3 (dimer)	-0.01	0.11	0.19	4	-0.29	38	42
GAB1/CRKL/SHP2/PI3K	-0.012	0.15	-10000	0	-0.39	46	46
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.01	0.15	0.29	3	-0.41	43	46
PTPN11	0.04	0.009	-10000	0	0	27	27
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.038	0.012	-10000	0	0	50	50
PTEN	0.039	0.011	-10000	0	0	38	38
ELK1	0.014	0.12	0.32	54	-10000	0	54
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.013	0.083	0.15	2	-0.22	49	51
PAK1	0.01	0.098	0.36	7	-0.69	4	11
HGF/MET/RANBP10	0.025	0.076	-10000	0	-0.12	104	104
HRAS	-0.072	0.22	-10000	0	-0.48	119	119
DOCK1	-0.033	0.14	0.26	7	-0.42	43	50
GAB1	-0.029	0.15	0.25	1	-0.46	41	42
CRK	-0.028	0.14	0.27	4	-0.42	43	47
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.056	0.19	-10000	0	-0.42	115	115
JUN	0.036	0.015	-10000	0	0	80	80
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.02	0.072	0.096	2	-0.16	103	105
PIK3R1	0.034	0.017	-10000	0	0	108	108
cell morphogenesis	-0.009	0.15	0.26	34	-0.33	45	79
GRB2/SHC	0.018	0.096	0.19	3	-0.16	106	109
FOS	0.026	0.02	-10000	0	0	207	207
GLMN	0.005	0.007	0.069	7	-10000	0	7
cell motility	0.013	0.12	0.31	54	-10000	0	54
HGF/MET/MUC20	0.014	0.064	-10000	0	-0.11	105	105
cell migration	0.017	0.095	0.19	3	-0.16	106	109
GRB2	0.041	0.007	-10000	0	0	17	17
CBL	0.04	0.008	-10000	0	0	23	23
MET/RANBP10	0.01	0.073	-10000	0	-0.13	105	105
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.017	0.081	-10000	0	-0.18	81	81
MET/MUC20	-0.004	0.061	-10000	0	-0.13	107	107
RAP1B	-0.034	0.13	0.27	2	-0.39	40	42
RAP1A	-0.039	0.13	0.3	2	-0.4	43	45
HGF/MET/RANBP9	0.026	0.078	-10000	0	-0.12	102	102
RAF1	-0.072	0.21	-10000	0	-0.46	120	120
STAT3	-0.009	0.11	0.19	4	-0.3	34	38
cell proliferation	-0.031	0.14	0.26	7	-0.3	81	88
RPS6KB1	-0.012	0.085	-10000	0	-0.32	30	30
MAPK3	-0.008	0.12	0.62	14	-10000	0	14
MAPK1	0.029	0.2	0.71	40	-10000	0	40
RANBP9	0.038	0.012	-10000	0	0	53	53
MAPK8	-0.022	0.15	-10000	0	-0.4	51	51
SRC	-0.006	0.092	0.2	9	-0.18	83	92
PI3K	0	0.096	0.19	3	-0.18	96	99
MET/Glomulin	0.012	0.047	-10000	0	-0.12	47	47
SOS1	0.038	0.013	-10000	0	0	56	56
MAP2K1	-0.071	0.2	-10000	0	-0.44	119	119
MET	0.027	0.02	-10000	0	0	198	198
MAP4K1	-0.022	0.15	0.29	1	-0.43	44	45
PTK2	0.027	0.02	-10000	0	0	204	204
MAP2K2	-0.072	0.19	-10000	0	-0.43	120	120
BAD	-0.003	0.079	0.34	2	-0.7	4	6
MAP2K4	-0.026	0.13	0.26	2	-0.37	46	48
SHP2/GRB2/SOS1/GAB1	-0.013	0.16	-10000	0	-0.36	54	54
INPPL1	0.04	0.009	-10000	0	0	30	30
PXN	0.041	0.007	-10000	0	0	14	14
SH3KBP1	0.041	0.007	-10000	0	0	16	16
HGS	-0.026	0.071	0.084	2	-0.16	112	114
PLCgamma1/PKC	0.026	0.022	-10000	0	-0.13	10	10
HGF	0.04	0.009	-10000	0	0	29	29
RASA1	0.037	0.014	-10000	0	0	71	71
NCK1	0.036	0.015	-10000	0	0	80	80
PTPRJ	0.039	0.01	-10000	0	0	35	35
NCK/PLCgamma1	0.016	0.095	0.19	3	-0.17	97	100
PDPK1	0.002	0.076	-10000	0	-0.77	4	4
HGF/MET/SHIP	0.014	0.064	-10000	0	-0.11	105	105

×

Signaling events mediated by PTP1B

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
PDGFRB	0.037	0.013	-10000	0	0	64	64
Jak2/Leptin Receptor	-0.017	0.14	-10000	0	-0.38	56	56
PTP1B/AKT1	-0.034	0.11	-10000	0	-0.24	81	81
FYN	0.034	0.016	-10000	0	0	103	103
p210 bcr-abl/PTP1B	-0.052	0.11	-10000	0	-0.26	86	86
EGFR	0.036	0.017	-10000	0	-0.004	83	83
EGF/EGFR	-0.025	0.12	-10000	0	-0.24	84	84
CSF1	0.035	0.015	-10000	0	0	89	89
AKT1	0.039	0.011	-10000	0	0	37	37
INSR	0.038	0.012	-10000	0	0	53	53
PTP1B/N-cadherin	-0.053	0.12	-10000	0	-0.25	119	119
Insulin Receptor/Insulin	-0.008	0.11	-10000	0	-0.22	61	61
HCK	0.036	0.015	-10000	0	0	80	80
CRK	0.038	0.012	-10000	0	0	52	52
TYK2	-0.036	0.12	0.23	21	-0.26	67	88
EGF	0.037	0.017	-10000	0	-0.007	69	69
YES1	0.038	0.013	-10000	0	0	57	57
CAV1	-0.035	0.11	-10000	0	-0.24	72	72
TXN	0.038	0.012	-10000	0	0	49	49
PTP1B/IRS1/GRB2	-0.027	0.13	-10000	0	-0.25	89	89
cell migration	0.052	0.11	0.26	86	-10000	0	86
STAT3	0.038	0.013	-10000	0	0	56	56
PRLR	0.038	0.017	-10000	0	-10000	0	0
ITGA2B	0.039	0.009	-10000	0	0	30	30
CSF1R	0.035	0.016	-10000	0	0	98	98
Prolactin Receptor/Prolactin	0.055	0.029	-10000	0	-10000	0	0
FGR	0.041	0.007	-10000	0	0	17	17
PTP1B/p130 Cas	-0.036	0.12	-10000	0	-0.25	84	84
Crk/p130 Cas	-0.029	0.12	-10000	0	-0.25	79	79
DOK1	-0.037	0.11	-10000	0	-0.25	66	66
JAK2	-0.03	0.14	-10000	0	-0.39	58	58
Jak2/Leptin Receptor/Leptin	-0.024	0.14	0.26	1	-0.28	69	70
PIK3R1	0.034	0.017	-10000	0	0	108	108
PTPN1	-0.052	0.12	-10000	0	-0.26	86	86
LYN	0.036	0.015	-10000	0	0	83	83
CDH2	0.02	0.021	-10000	0	0	299	299
SRC	0.01	0.083	-10000	0	-0.5	10	10
ITGB3	0.032	0.017	-10000	0	0	121	121
CAT1/PTP1B	-0.037	0.13	0.25	5	-0.29	69	74
CAPN1	0.039	0.009	-10000	0	0	25	25
CSK	0.04	0.008	-10000	0	0	21	21
PI3K	-0.01	0.11	-10000	0	-0.22	55	55
mol:H2O2	0.002	0.005	0.03	1	-10000	0	1
STAT3 (dimer)	-0.02	0.13	0.25	1	-0.26	69	70
negative regulation of transcription	-0.029	0.14	-10000	0	-0.39	58	58
FCGR2A	0.032	0.018	-10000	0	0	129	129
FER	0.037	0.012	-10000	0	0	55	55
alphaIIb/beta3 Integrin	0.038	0.05	-10000	0	-0.14	34	34
BLK	0.033	0.017	-10000	0	0	117	117
Insulin Receptor/Insulin/Shc	0.068	0.037	-10000	0	-0.12	5	5
RHOA	0.04	0.007	-10000	0	0	14	14
LEPR	0.039	0.012	-10000	0	0	45	45
BCAR1	0.036	0.014	-10000	0	0	76	76
p210 bcr-abl/Grb2	0.041	0.007	-10000	0	0	17	17
mol:NADPH	-0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.007	0.12	0.22	8	-0.29	47	55
PRL	0.042	0.012	-10000	0	-10000	0	0
SOCS3	-0.02	0.25	-10000	0	-1.1	26	26
SPRY2	0.023	0.021	-10000	0	0	247	247
Insulin Receptor/Insulin/IRS1	0.07	0.038	-10000	0	-0.12	8	8
CSF1/CSF1R	-0.044	0.13	-10000	0	-0.27	90	90
Ras protein signal transduction	0.006	0.071	0.61	6	-10000	0	6
IRS1	0.04	0.008	-10000	0	0	22	22
INS	0.04	0.01	-10000	0	0	30	30
LEP	0.039	0.01	-10000	0	0	33	33
STAT5B	-0.041	0.12	-10000	0	-0.28	80	80
STAT5A	-0.043	0.12	-10000	0	-0.27	84	84
GRB2	0.041	0.007	-10000	0	0	17	17
PDGFB-D/PDGFRB	-0.043	0.12	-10000	0	-0.25	87	87
CSN2	0.042	0.068	0.43	2	-10000	0	2
PIK3CA	0.03	0.019	-10000	0	0	155	155
LAT	-0.058	0.19	-10000	0	-0.48	87	87
YBX1	0.048	0.02	-10000	0	-0.28	1	1
LCK	0.04	0.009	-10000	0	0	29	29
SHC1	0.04	0.01	-10000	0	0	31	31
NOX4	0.021	0.021	-10000	0	0	281	281

×

Canonical Wnt signaling 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
HDAC1	0.054	0.062	0.15	118	-0.033	29	147
AES	0.053	0.056	0.14	122	-0.032	14	136
FBXW11	0.04	0.009	-10000	0	0	25	25
mol:GTP	0.001	0.003	0.033	1	-10000	0	1
LRP6/FZD1	0.041	0.049	-10000	0	-0.14	32	32
SMAD4	0.038	0.012	-10000	0	0	49	49
DKK2	0.039	0.012	-10000	0	0	47	47
TLE1	0.053	0.052	0.13	118	-0.033	12	130
MACF1	0.033	0.017	-10000	0	0	118	118
CTNNB1	0.033	0.12	0.29	27	-0.4	12	39
WIF1	0.04	0.01	-10000	0	-0.001	32	32
beta catenin/RanBP3	0.099	0.22	0.47	119	-0.43	7	126
KREMEN2	0.04	0.009	-10000	0	0	27	27
DKK1	0.039	0.011	-10000	0	0	44	44
beta catenin/beta TrCP1	0.054	0.12	0.3	28	-0.38	11	39
FZD1	0.041	0.007	-10000	0	0	17	17
AXIN2	-0.047	0.22	0.68	7	-0.79	28	35
AXIN1	0.042	0.004	-10000	0	0	4	4
RAN	0.042	0.007	0.076	1	0	13	14
Axin1/APC/GSK3/beta catenin	0.047	0.087	0.41	1	-0.55	7	8
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.025	0.17	0.32	8	-0.41	61	69
Axin1/APC/GSK3	0.03	0.07	0.21	14	-0.24	11	25
Axin1/APC/GSK3/beta catenin/Macf1	0.022	0.088	0.28	13	-0.27	9	22
HNF1A	0.019	0.051	0.091	135	-10000	0	135
CTBP1	0.053	0.053	0.14	116	-0.033	12	128
MYC	0.043	0.55	0.63	163	-1.1	74	237
RANBP3	0.04	0.011	0.076	1	0	40	41
DKK2/LRP6/Kremen 2	0.057	0.054	-10000	0	-0.12	29	29
NKD1	0.038	0.012	-10000	0	0	49	49
TCF4	0.055	0.059	0.14	117	-0.033	13	130
TCF3	0.053	0.055	0.14	120	-0.034	13	133
WNT1/LRP6/FZD1/Axin1	0.08	0.061	-10000	0	-0.11	31	31
Ran/GTP	0.031	0.013	0.1	1	-0.12	3	4
CtBP/CBP/TCF/TLE1/AES	0.058	0.31	0.57	110	-0.36	35	145
LEF1	0.037	0.051	0.14	74	-0.033	13	87
DVL1	0.033	0.076	0.23	11	-0.3	13	24
CSNK2A1	0.038	0.013	-10000	0	0	54	54
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.066	0.19	-10000	0	-0.43	81	81
DKK1/LRP6/Kremen 2	0.056	0.054	-10000	0	-0.12	28	28
LRP6	0.034	0.017	-10000	0	0	107	107
CSNK1A1	0.059	0.065	0.15	130	-0.033	30	160
NLK	0.031	0.025	-10000	0	-0.024	83	83
CCND1	-0.18	0.51	0.71	17	-1.2	96	113
WNT1	0.041	0.006	-10000	0	0	13	13
GSK3A	0.039	0.011	0.065	1	0	38	39
GSK3B	0.04	0.009	-10000	0	0	26	26
FRAT1	0.04	0.009	-10000	0	-0.002	25	25
PPP2R5D	0.035	0.062	0.24	2	-0.29	12	14
APC	-0.005	0.082	0.21	61	-10000	0	61
WNT1/LRP6/FZD1	0.019	0.062	0.18	2	-0.24	8	10
CREBBP	0.054	0.055	0.14	122	-0.033	15	137

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.042	0.004	-10000	0	0	6	6
PTK2	0.027	0.02	-10000	0	0	204	204
CRKL	-0.022	0.052	0.12	13	-0.13	71	84
GRB2/SOS1/SHC	0.065	0.051	-10000	0	-0.13	26	26
HRAS	0.04	0.01	-10000	0	0	31	31
IRS1/Crk	0.011	0.057	-10000	0	-0.12	75	75
IGF-1R heterotetramer/IGF1/PTP1B	0.034	0.073	-10000	0	-0.12	75	75
AKT1	0	0.092	0.18	83	-0.18	14	97
BAD	-0.007	0.085	0.16	79	-0.17	14	93
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.02	0.051	0.11	12	-0.13	66	78
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.011	0.069	0.2	4	-0.13	96	100
RAF1	0.016	0.12	0.28	9	-0.48	13	22
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.044	0.088	0.21	2	-0.13	96	98
YWHAZ	0.034	0.016	-10000	0	0	102	102
IGF-1R heterotetramer/IGF1/IRS1	0.018	0.068	0.18	2	-0.13	85	87
PIK3CA	0.03	0.019	-10000	0	0	155	155
RPS6KB1	0	0.096	0.18	89	-0.19	20	109
GNB2L1	0.041	0.005	-10000	0	0	7	7
positive regulation of MAPKKK cascade	0.014	0.11	0.28	13	-0.41	10	23
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.017	-10000	0	0	108	108
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
HRAS/GTP	0.014	0.068	-10000	0	-0.13	82	82
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.061	0.091	-10000	0	-0.12	85	85
IGF-1R heterotetramer	0.033	0.024	0.1	2	-0.052	16	18
IGF-1R heterotetramer/IGF1/IRS/Nck	0.038	0.076	0.2	2	-0.13	85	87
Crk/p130 Cas/Paxillin	0.043	0.082	0.25	9	-0.13	72	81
IGF1R	0.034	0.024	0.1	2	-0.052	16	18
IGF1	0.027	0.035	0.1	2	-0.053	70	72
IRS2/Crk	0.009	0.055	0.17	1	-0.13	62	63
PI3K	0.024	0.083	0.21	2	-0.12	95	97
apoptosis	-0.002	0.09	0.18	6	-0.23	28	34
HRAS/GDP	0.029	0.01	-10000	0	-0.13	1	1
PRKCD	-0.011	0.093	0.21	6	-0.21	69	75
RAF1/14-3-3 E	0.032	0.11	0.29	11	-0.41	13	24
BAD/14-3-3	0.002	0.093	0.23	28	-0.18	8	36
PRKCZ	0.001	0.095	0.18	92	-0.17	15	107
Crk/p130 Cas/Paxillin/FAK1	0.01	0.08	0.19	18	-0.16	42	60
PTPN1	0.038	0.012	-10000	0	0	54	54
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.011	0.094	-10000	0	-0.21	82	82
BCAR1	0.036	0.014	-10000	0	0	76	76
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.054	0.078	-10000	0	-0.11	77	77
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.038	0.013	-10000	0	0	56	56
IRS1/NCK2	0.025	0.069	0.14	16	-0.12	85	101
GRB10	0.04	0.008	-10000	0	0	23	23
PTPN11	-0.021	0.052	0.11	13	-0.13	68	81
IRS1	0.004	0.062	0.13	17	-0.13	85	102
IRS2	-0.021	0.052	0.11	14	-0.13	71	85
IGF-1R heterotetramer/IGF1	0.02	0.076	0.16	2	-0.16	76	78
GRB2	0.041	0.007	-10000	0	0	17	17
PDPK1	0.008	0.099	0.19	90	-0.18	13	103
YWHAE	0.038	0.013	-10000	0	0	58	58
PRKD1	-0.012	0.097	0.2	8	-0.22	74	82
SHC1	0.04	0.01	-10000	0	0	31	31

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.036	0.015	-10000	0	0	78	78
GNB1/GNG2	0.015	0.12	0.23	2	-0.26	46	48
mol:DAG	-0.006	0.1	0.22	5	-0.25	42	47
PLCG1	-0.007	0.1	0.22	5	-0.26	42	47
YES1	-0.017	0.095	0.2	1	-0.27	44	45
FZD3	0.029	0.019	-10000	0	0	168	168
FZD6	0.029	0.019	-10000	0	0	170	170
G protein	0.029	0.13	0.25	40	-0.26	41	81
MAP3K7	-0.026	0.086	0.18	11	-0.23	40	51
mol:Ca2+	-0.006	0.1	0.21	5	-0.25	42	47
mol:IP3	-0.006	0.1	0.22	5	-0.25	42	47
NLK	-0.032	0.27	-10000	0	-0.87	51	51
GNB1	0.041	0.005	-10000	0	0	7	7
CAMK2A	-0.017	0.092	0.19	6	-0.24	40	46
MAP3K7IP1	0.038	0.012	-10000	0	0	54	54
Noncanonical Wnts/FZD	-0.019	0.096	-10000	0	-0.2	94	94
CSNK1A1	0.04	0.009	-10000	0	0	26	26
GNAS	-0.01	0.1	0.2	21	-0.2	86	107
GO:0007205	-0.013	0.096	0.2	6	-0.25	44	50
WNT6	0.041	0.006	-10000	0	0	13	13
WNT4	0.041	0.007	-10000	0	0	18	18
NFAT1/CK1 alpha	0.005	0.12	0.29	9	-0.27	41	50
GNG2	0.039	0.01	-10000	0	0	34	34
WNT5A	0.035	0.015	-10000	0	0	91	91
WNT11	0.033	0.017	-10000	0	0	124	124
CDC42	-0.019	0.095	0.19	7	-0.26	43	50

×

FoxO family 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
G6PC	-0.002	0.065	-10000	0	-10000	0	0
PLK1	-0.15	0.38	-10000	0	-0.86	93	93
CDKN1B	-0.046	0.2	0.4	2	-0.38	81	83
FOXO3	-0.14	0.35	-10000	0	-0.57	179	179
KAT2B	-0.008	0.028	0.043	4	-0.045	186	190
FOXO1/SIRT1	0.015	0.078	-10000	0	-0.23	16	16
CAT	-0.16	0.4	0.65	1	-0.93	87	88
CTNNB1	0.04	0.01	-10000	0	0	31	31
AKT1	0.012	0.056	-10000	0	-0.064	155	155
FOXO1	-0.005	0.07	-10000	0	-0.24	12	12
MAPK10	0	0.047	0.19	7	-0.13	20	27
mol:GTP	0	0.003	-10000	0	-10000	0	0
FOXO4	-0.025	0.12	0.24	2	-0.32	49	51
response to oxidative stress	-0.007	0.03	0.061	1	-0.052	105	106
FOXO3A/SIRT1	-0.13	0.34	0.41	1	-0.55	185	186
XPO1	0.039	0.011	-10000	0	0	39	39
EP300	0.038	0.015	-10000	0	-10000	0	0
BCL2L11	0.01	0.11	-10000	0	-0.93	6	6
FOXO1/SKP2	0.012	0.075	-10000	0	-0.24	17	17
mol:GDP	-0.007	0.03	0.061	1	-0.052	105	106
RAN	0.041	0.007	-10000	0	0	13	13
GADD45A	-0.077	0.28	-10000	0	-0.81	50	50
YWHAQ	0.04	0.009	-10000	0	0	28	28
FOXO1/14-3-3 family	0.014	0.13	0.27	2	-0.34	41	43
MST1	0.011	0.056	-10000	0	-0.063	191	191
CSNK1D	0.04	0.009	-10000	0	0	28	28
CSNK1E	0.038	0.013	-10000	0	0	57	57
FOXO4/14-3-3 family	0.002	0.14	-10000	0	-0.38	42	42
YWHAB	0.038	0.012	-10000	0	0	52	52
MAPK8	0.001	0.052	0.19	11	-0.13	21	32
MAPK9	-0.001	0.052	0.19	10	-0.14	20	30
YWHAG	0.04	0.009	-10000	0	0	25	25
YWHAE	0.038	0.013	-10000	0	0	58	58
YWHAZ	0.034	0.016	-10000	0	0	102	102
SIRT1	0.037	0.018	0.12	2	-0.035	24	26
SOD2	-0.12	0.3	-10000	0	-0.64	103	103
RBL2	-0.12	0.33	-10000	0	-0.77	78	78
RAL/GDP	0.031	0.056	-10000	0	-0.1	45	45
CHUK	0.012	0.054	-10000	0	-0.063	173	173
Ran/GTP	0.027	0.019	-10000	0	-0.13	3	3
CSNK1G2	0.037	0.013	-10000	0	0	64	64
RAL/GTP	0.031	0.057	-10000	0	-0.089	54	54
CSNK1G1	0.041	0.008	-10000	0	0	19	19
FASLG	0.017	0.065	-10000	0	-1.2	1	1
SKP2	0.036	0.014	-10000	0	0	73	73
USP7	0.038	0.012	-10000	0	0	50	50
IKBKB	0.011	0.054	-10000	0	-0.062	181	181
CCNB1	-0.18	0.43	-10000	0	-0.98	101	101
FOXO1-3a-4/beta catenin	-0.06	0.2	-10000	0	-0.39	98	98
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.074	-10000	0	-0.24	17	17
CSNK1A1	0.04	0.009	-10000	0	0	26	26
SGK1	-0.008	0.028	0.043	4	-0.045	186	190
CSNK1G3	0.039	0.011	-10000	0	0	38	38
Ran/GTP/Exportin 1	0.046	0.038	-10000	0	-0.11	24	24
ZFAND5	-0.019	0.1	0.22	2	-0.27	49	51
SFN	0.036	0.015	-10000	0	0	86	86
CDK2	0.04	0.014	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.006	0.14	0.21	3	-0.33	59	62
CREBBP	0.04	0.013	-10000	0	-10000	0	0
FBXO32	-0.2	0.54	0.48	6	-1.1	144	150
BCL6	-0.13	0.35	-10000	0	-0.92	68	68
RALB	0.04	0.009	-10000	0	0	26	26
RALA	0.04	0.01	-10000	0	0	30	30
YWHAH	0.037	0.013	-10000	0	0	60	60

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.008	0.11	0.15	56	-0.28	41	97
adherens junction organization	-0.026	0.13	0.18	6	-0.36	50	56
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.011	0.11	0.21	9	-0.28	31	40
FMN1	-0.023	0.12	0.16	6	-0.28	65	71
mol:IP3	0.003	0.098	0.16	60	-0.23	45	105
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.13	0.17	5	-0.29	65	70
CTNNB1	0.041	0.011	0.069	3	0	31	34
AKT1	-0.015	0.092	0.19	10	-0.25	44	54
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.15	-10000	0	-0.4	43	43
CTNND1	0.042	0.009	-10000	0	-0.002	18	18
mol:PI-4-5-P2	-0.02	0.12	0.2	4	-0.28	64	68
VASP	-0.021	0.12	0.16	5	-0.28	64	69
ZYX	-0.016	0.11	0.16	6	-0.29	51	57
JUB	-0.022	0.12	0.16	6	-0.29	64	70
EGFR(dimer)	-0.005	0.13	0.2	1	-0.31	56	57
E-cadherin/beta catenin-gamma catenin	0.05	0.06	-10000	0	-0.11	46	46
mol:PI-3-4-5-P3	-0.004	0.1	0.22	2	-0.26	45	47
PIK3CA	0.03	0.02	-10000	0	-0.001	159	159
PI3K	-0.004	0.11	0.22	2	-0.27	45	47
FYN	-0.012	0.12	0.2	8	-0.28	61	69
mol:Ca2+	0.003	0.096	0.16	60	-0.22	45	105
JUP	0.038	0.014	-10000	0	0	67	67
PIK3R1	0.035	0.018	-10000	0	0	109	109
mol:DAG	0.003	0.098	0.16	60	-0.23	45	105
CDH1	0.035	0.016	-10000	0	0	98	98
RhoA/GDP	0.013	0.11	0.22	12	-0.27	33	45
establishment of polarity of embryonic epithelium	-0.02	0.12	0.2	3	-0.28	64	67
SRC	0.039	0.01	-10000	0	0	36	36
RAC1	0.039	0.01	-10000	0	0	34	34
RHOA	0.041	0.007	-10000	0	0	14	14
EGFR	0.037	0.014	-10000	0	0	72	72
CASR	-0.004	0.093	0.15	62	-0.24	35	97
RhoA/GTP	0.015	0.1	0.2	4	-0.24	35	39
AKT2	-0.016	0.092	0.18	8	-0.25	47	55
actin cable formation	-0.025	0.11	0.21	7	-0.32	46	53
apoptosis	0.001	0.11	0.27	45	-0.17	64	109
CTNNA1	0.041	0.012	-10000	0	-0.001	39	39
mol:GDP	-0.005	0.1	0.16	58	-0.27	35	93
PIP5K1A	-0.022	0.12	0.16	5	-0.29	64	69
PLCG1	0.002	0.1	0.16	60	-0.23	45	105
Rac1/GTP	0.004	0.13	-10000	0	-0.3	54	54
homophilic cell adhesion	0	0.004	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.032	0.019	-10000	0	0	143	143
ELF1	0.047	0.023	-10000	0	-0.27	2	2
CCNA2	0.032	0.018	-10000	0	0	135	135
PIK3CA	0.031	0.019	-10000	0	0	155	155
JAK3	0.038	0.013	-10000	0	-0.001	56	56
PIK3R1	0.034	0.017	-10000	0	-0.001	110	110
JAK1	0.04	0.011	-10000	0	-0.002	36	36
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.001	0.14	-10000	0	-0.33	47	47
SHC1	0.04	0.01	-10000	0	-0.001	32	32
SP1	0.044	0.043	-10000	0	-0.28	9	9
IL2RA	0.02	0.032	-10000	0	-0.49	2	2
IL2RB	0.037	0.015	-10000	0	-0.001	77	77
SOS1	0.038	0.013	-10000	0	-0.001	58	58
IL2RG	0.029	0.02	-10000	0	0	184	184
G1/S transition of mitotic cell cycle	-0.039	0.18	0.29	4	-0.59	27	31
PTPN11	0.04	0.011	-10000	0	-0.004	31	31
CCND2	0.012	0.058	-10000	0	-0.49	7	7
LCK	0.04	0.011	-10000	0	-0.004	33	33
GRB2	0.041	0.009	-10000	0	-0.003	19	19
IL2	0.039	0.013	-10000	0	-0.002	49	49
CDK6	0.032	0.018	-10000	0	0	129	129
CCND3	0.004	0.14	-10000	0	-0.55	14	14

×

IL4-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
BCL2L1	-0.066	0.49	-10000	0	-1	69	69
STAT6 (cleaved dimer)	-0.11	0.45	-10000	0	-0.95	86	86
IGHG1	0.034	0.23	0.45	4	-0.57	12	16
IGHG3	-0.069	0.45	-10000	0	-0.93	79	79
AKT1	-0.055	0.37	-10000	0	-0.81	71	71
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.044	0.36	-10000	0	-0.86	68	68
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.051	0.4	-10000	0	-0.93	65	65
THY1	-0.23	0.66	0.78	1	-1.2	157	158
MYB	0.034	0.017	-10000	0	0	111	111
HMGA1	0.037	0.014	-10000	0	0	72	72
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.025	0.37	0.53	2	-0.72	75	77
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.055	0.4	-10000	0	-0.92	67	67
SP1	0.022	0.073	-10000	0	-0.13	104	104
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.001	0.05	-10000	0	-0.086	2	2
STAT6 (dimer)/ETS1	-0.086	0.46	-10000	0	-0.96	80	80
SOCS1	-0.03	0.35	0.52	1	-0.66	68	69
SOCS3	-0.034	0.37	-10000	0	-0.88	51	51
FCER2	-0.032	0.39	-10000	0	-0.83	44	44
PARP14	0.033	0.019	-10000	0	-10000	0	0
CCL17	-0.062	0.47	-10000	0	-1	65	65
GRB2	0.041	0.007	-10000	0	0	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.011	0.3	-10000	0	-0.64	59	59
T cell proliferation	-0.086	0.49	-10000	0	-1	82	82
IL4R/JAK1	-0.079	0.49	-10000	0	-1	80	80
EGR2	-0.059	0.48	-10000	0	-1	63	63
JAK2	0.033	0.073	0.17	4	-10000	0	4
JAK3	0.034	0.026	-10000	0	-0.038	44	44
PIK3R1	0.034	0.017	-10000	0	0	108	108
JAK1	0.041	0.041	0.11	4	-0.036	23	27
COL1A2	-0.15	0.56	-10000	0	-1.3	108	108
CCL26	-0.072	0.49	-10000	0	-1	69	69
IL4R	-0.068	0.52	-10000	0	-1.1	75	75
PTPN6	0.006	0.043	-10000	0	-0.074	2	2
IL13RA2	-0.061	0.47	-10000	0	-1	67	67
IL13RA1	0.036	0.076	0.18	7	-10000	0	7
IRF4	0.058	0.15	-10000	0	-1.3	1	1
ARG1	0.05	0.19	-10000	0	-0.69	6	6
CBL	-0.027	0.35	0.57	2	-0.68	74	76
GTF3A	0.013	0.08	-10000	0	-0.13	123	123
PIK3CA	0.03	0.019	-10000	0	0	155	155
IL13RA1/JAK2	0.043	0.12	0.25	5	-0.18	25	30
IRF4/BCL6	0.043	0.14	-10000	0	-1.2	1	1
CD40LG	0.049	0.01	-10000	0	-0.12	1	1
MAPK14	-0.029	0.36	-10000	0	-0.72	73	73
mitosis	-0.046	0.35	0.5	1	-0.76	71	72
STAT6	-0.064	0.54	0.78	2	-1.1	78	80
SPI1	0.045	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.05	0.34	-10000	0	-0.73	72	72
STAT6 (dimer)	-0.062	0.54	0.78	2	-1.1	78	80
STAT6 (dimer)/PARP14	-0.1	0.48	-10000	0	-1	80	80
mast cell activation	-0.004	0.019	-10000	0	-0.043	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.075	0.39	-10000	0	-0.88	73	73
FRAP1	-0.055	0.37	-10000	0	-0.81	71	71
LTA	-0.06	0.47	-10000	0	-0.98	71	71
FES	0.04	0.008	-10000	0	0	22	22
T-helper 1 cell differentiation	0.058	0.53	1.1	78	-0.78	2	80
CCL11	-0.096	0.5	-10000	0	-1	83	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.048	0.38	-10000	0	-0.87	68	68
IL2RG	0.027	0.025	-10000	0	-0.04	19	19
IL10	-0.058	0.48	-10000	0	-1	66	66
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.01	-10000	0	0	33	33
IL4	0.038	0.23	-10000	0	-0.93	14	14
IL5	-0.063	0.47	-10000	0	-1	62	62
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.047	0.46	0.7	2	-0.89	81	83
COL1A1	-0.22	0.65	-10000	0	-1.3	143	143
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.085	0.49	-10000	0	-1.1	64	64
IL2R gamma/JAK3	0.02	0.074	-10000	0	-0.13	92	92
TFF3	-0.067	0.49	-10000	0	-1	75	75
ALOX15	-0.062	0.47	-10000	0	-1	64	64
MYBL1	0.036	0.014	-10000	0	0	73	73
T-helper 2 cell differentiation	-0.1	0.47	-10000	0	-0.94	90	90
SHC1	0.04	0.01	-10000	0	0	31	31
CEBPB	0.04	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.052	0.4	-10000	0	-0.89	71	71
mol:PI-3-4-5-P3	-0.054	0.37	-10000	0	-0.81	71	71
PI3K	-0.064	0.4	-10000	0	-0.89	71	71
DOK2	0.032	0.018	-10000	0	0	135	135
ETS1	0.001	0.047	-10000	0	-0.099	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.008	0.29	-10000	0	-0.61	64	64
ITGB3	-0.096	0.54	-10000	0	-1.1	85	85
PIGR	-0.058	0.49	-10000	0	-1	67	67
IGHE	-0.002	0.089	0.19	39	-0.19	23	62
MAPKKK cascade	-0.007	0.29	-10000	0	-0.6	64	64
BCL6	0.03	0.018	-10000	0	0	146	146
OPRM1	-0.063	0.47	-10000	0	-1	58	58
RETNLB	-0.056	0.48	-10000	0	-0.98	73	73
SELP	-0.057	0.48	-10000	0	-1	63	63
AICDA	-0.051	0.45	-10000	0	-0.97	62	62

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.01	0.1	-10000	0	-0.13	144	144
SMAD6-7/SMURF1	0.07	0.04	-10000	0	-0.15	8	8
NOG	0.038	0.012	-10000	0	0	50	50
SMAD9	0.006	0.12	-10000	0	-0.42	37	37
SMAD4	0.038	0.012	-10000	0	0	49	49
SMAD5	-0.002	0.098	0.22	2	-0.28	38	40
BMP7/USAG1	-0.02	0.084	-10000	0	-0.16	134	134
SMAD5/SKI	0.011	0.11	0.24	1	-0.28	40	41
SMAD1	0.003	0.096	-10000	0	-0.3	31	31
BMP2	0.038	0.012	-10000	0	0	49	49
SMAD1/SMAD1/SMAD4	0.027	0.1	-10000	0	-0.3	28	28
BMPR1A	0.037	0.013	-10000	0	0	65	65
BMPR1B	0.031	0.019	-10000	0	0	153	153
BMPR1A-1B/BAMBI	0.007	0.088	-10000	0	-0.14	121	121
AHSG	0.034	0.017	-10000	0	0	109	109
CER1	0.038	0.012	-10000	0	0	49	49
BMP2-4/CER1	0.06	0.045	-10000	0	-0.12	11	11
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.008	0.11	0.19	1	-0.26	58	59
BMP2-4 (homodimer)	0.047	0.036	-10000	0	-0.14	11	11
RGMB	0.039	0.011	-10000	0	0	42	42
BMP6/BMPR2/BMPR1A-1B	0.05	0.085	-10000	0	-0.13	82	82
RGMA	0.039	0.01	-10000	0	0	34	34
SMURF1	0.041	0.008	-10000	0	0	19	19
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.002	0.081	0.17	2	-0.24	34	36
BMP2-4/USAG1	0.022	0.07	-10000	0	-0.12	71	71
SMAD6/SMURF1/SMAD5	0.01	0.11	0.24	1	-0.28	40	41
SOSTDC1	0.023	0.021	-10000	0	0	255	255
BMP7/BMPR2/BMPR1A-1B	0.008	0.1	-10000	0	-0.14	154	154
SKI	0.042	0.003	-10000	0	0	3	3
BMP6 (homodimer)	0.037	0.013	-10000	0	0	63	63
HFE2	0.041	0.005	-10000	0	0	8	8
ZFYVE16	0.035	0.016	-10000	0	0	93	93
MAP3K7	0.038	0.012	-10000	0	0	47	47
BMP2-4/CHRD	0.052	0.046	-10000	0	-0.12	8	8
SMAD5/SMAD5/SMAD4	0.008	0.11	0.24	1	-0.28	39	40
MAPK1	0.039	0.012	-10000	0	0	46	46
TAK1/TAB family	0.032	0.12	-10000	0	-0.24	39	39
BMP7 (homodimer)	0.022	0.021	-10000	0	0	271	271
NUP214	0.039	0.01	-10000	0	0	33	33
BMP6/FETUA	0.045	0.028	-10000	0	-10000	0	0
SMAD1/SKI	0.023	0.1	-10000	0	-0.29	32	32
SMAD6	0.04	0.01	-10000	0	0	32	32
CTDSP2	0.039	0.011	-10000	0	0	42	42
BMP2-4/FETUA	0.053	0.045	-10000	0	-0.12	8	8
MAP3K7IP1	0.038	0.012	-10000	0	0	54	54
GREM1	0.035	0.016	-10000	0	0	98	98
BMPR2 (homodimer)	0.04	0.009	-10000	0	0	29	29
GADD34/PP1CA	0.057	0.056	-10000	0	-0.12	35	35
BMPR1A-1B (homodimer)	0.016	0.078	-10000	0	-0.15	90	90
CHRDL1	0.026	0.02	-10000	0	0	213	213
ENDOFIN/SMAD1	0.019	0.1	-10000	0	-0.29	31	31
SMAD6-7/SMURF1/SMAD1	0.049	0.11	-10000	0	-0.3	28	28
SMAD6/SMURF1	0.04	0.008	-10000	0	0	19	19
BAMBI	0.029	0.019	-10000	0	0	172	172
SMURF2	0.039	0.01	-10000	0	0	35	35
BMP2-4/CHRDL1	0.019	0.077	-10000	0	-0.12	102	102
BMP2-4/GREM1	0.052	0.049	-10000	0	-0.12	16	16
SMAD7	0.039	0.011	-10000	0	0	45	45
SMAD8A/SMAD8A/SMAD4	0.019	0.13	-10000	0	-0.4	44	44
SMAD1/SMAD6	0.023	0.1	-10000	0	-0.3	30	30
TAK1/SMAD6	0.052	0.036	-10000	0	-0.14	15	15
BMP7	0.022	0.021	-10000	0	0	271	271
BMP6	0.037	0.013	-10000	0	0	63	63
MAP3K7IP2	0.038	0.013	-10000	0	0	59	59
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.002	0.084	-10000	0	-0.24	35	35
PPM1A	0.041	0.007	-10000	0	0	16	16
SMAD1/SMURF2	0.021	0.1	-10000	0	-0.3	31	31
SMAD7/SMURF1	0.053	0.029	-10000	0	-0.14	8	8
CTDSPL	0.041	0.006	-10000	0	0	10	10
PPP1CA	0.041	0.006	-10000	0	0	13	13
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0.041	0.006	-10000	0	0	13	13
PPP1R15A	0.039	0.011	-10000	0	0	44	44
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.001	0.087	-10000	0	-0.25	35	35
CHRD	0.033	0.017	-10000	0	0	116	116
BMPR2	0.04	0.009	-10000	0	0	29	29
BMP2-4/BMPR2/BMPR1A-1B/RGM	0	0.087	-10000	0	-0.26	31	31
BMP4	0.036	0.014	-10000	0	0	75	75
FST	0.033	0.017	-10000	0	0	120	120
BMP2-4/NOG	0.058	0.05	-10000	0	-0.12	20	20
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.017	0.11	-10000	0	-0.14	150	150

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.041	0.087	-10000	0	-0.14	68	68
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.039	0.011	-10000	0	0	38	38
STAT1 (dimer)/Cbp/p300	0.005	0.12	0.28	6	-0.22	81	87
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.041	0.081	-10000	0	-0.15	69	69
antigen processing and presentation of peptide antigen via MHC class I	-0.025	0.093	-10000	0	-0.2	85	85
CaM/Ca2+	0.044	0.088	-10000	0	-0.14	65	65
RAP1A	0.039	0.01	-10000	0	0	35	35
STAT1 (dimer)/SHP2	0	0.093	0.19	19	-0.17	81	100
AKT1	0.005	0.1	0.19	71	-0.22	31	102
MAP2K1	-0.028	0.066	0.14	27	-0.18	34	61
MAP3K11	-0.022	0.072	0.16	34	-0.17	30	64
IFNGR1	0.035	0.021	0.083	2	-0.005	111	113
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.01	0.1	-10000	0	-0.29	42	42
Rap1/GTP	-0.044	0.057	0.068	13	-0.17	46	59
CRKL/C3G	0.056	0.018	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.063	0.091	-10000	0	-0.14	62	62
CEBPB	-0.029	0.16	0.28	1	-0.44	56	57
STAT3	0.038	0.013	-10000	0	0	56	56
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.048	0.16	-10000	0	-0.77	15	15
STAT1	-0.028	0.082	0.18	23	-0.2	50	73
CALM1	0.04	0.01	-10000	0	0	31	31
IFN-gamma (dimer)	0.032	0.025	0.085	2	-0.017	103	105
PIK3CA	0.03	0.019	-10000	0	0	155	155
STAT1 (dimer)/PIAS1	-0.009	0.093	0.23	8	-0.2	60	68
CEBPB/PTGES2/Cbp/p300	-0.011	0.12	-10000	0	-0.3	55	55
mol:Ca2+	0.036	0.085	-10000	0	-0.14	68	68
MAPK3	-0.021	0.14	-10000	0	-0.65	15	15
STAT1 (dimer)	-0.022	0.13	0.19	2	-0.28	81	83
MAPK1	-0.058	0.21	0.42	1	-0.74	42	43
JAK2	0.033	0.022	0.083	2	-0.007	114	116
PIK3R1	0.034	0.017	-10000	0	0	108	108
JAK1	0.036	0.022	0.082	1	-0.019	67	68
CAMK2D	0.036	0.015	-10000	0	0	82	82
DAPK1	-0.027	0.16	0.24	1	-0.48	48	49
SMAD7	-0.003	0.071	0.15	38	-0.13	50	88
CBL/CRKL/C3G	0.026	0.085	0.24	7	-0.17	33	40
PI3K	0.02	0.092	-10000	0	-0.17	63	63
IFNG	0.032	0.025	0.085	2	-0.017	103	105
apoptosis	-0.022	0.15	-10000	0	-0.42	53	53
CAMK2G	0.04	0.008	-10000	0	0	23	23
STAT3 (dimer)	0.038	0.013	-10000	0	0	56	56
CAMK2A	0.041	0.006	-10000	0	0	12	12
CAMK2B	0.041	0.007	-10000	0	0	18	18
FRAP1	-0.004	0.098	0.16	78	-0.21	34	112
PRKCD	0.002	0.11	0.2	59	-0.23	33	92
RAP1B	0.038	0.013	-10000	0	0	59	59
negative regulation of cell growth	-0.025	0.093	-10000	0	-0.2	85	85
PTPN2	0.04	0.008	-10000	0	0	20	20
EP300	0.036	0.014	-10000	0	0	73	73
IRF1	-0.046	0.097	0.22	7	-0.27	63	70
STAT1 (dimer)/PIASy	-0.029	0.087	0.19	21	-0.22	40	61
SOCS1	0.003	0.18	-10000	0	-1.1	15	15
mol:GDP	0.023	0.081	0.22	7	-0.16	33	40
CASP1	-0.023	0.08	0.16	15	-0.17	97	112
PTGES2	0.04	0.009	-10000	0	0	27	27
IRF9	-0.008	0.052	0.11	8	-0.12	54	62
mol:PI-3-4-5-P3	0.006	0.082	-10000	0	-0.17	66	66
RAP1/GDP	0.015	0.086	0.2	2	-0.18	46	48
CBL	-0.021	0.072	0.16	32	-0.18	26	58
MAP3K1	-0.02	0.07	0.16	28	-0.18	29	57
PIAS1	0.04	0.009	-10000	0	0	28	28
PIAS4	0.038	0.012	-10000	0	0	55	55
antigen processing and presentation of peptide antigen via MHC class II	-0.025	0.093	-10000	0	-0.2	85	85
PTPN11	-0.015	0.074	0.17	34	-0.17	33	67
CREBBP	0.038	0.013	-10000	0	0	54	54
RAPGEF1	0.04	0.008	-10000	0	0	23	23

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.031	0.1	0.21	18	-0.26	24	42
TBX21	-0.029	0.28	-10000	0	-0.74	45	45
B2M	0.038	0.014	-10000	0	-10000	0	0
TYK2	0.025	0.044	-10000	0	-0.052	81	81
IL12RB1	0.024	0.045	-10000	0	-0.052	92	92
GADD45B	-0.06	0.35	-10000	0	-0.95	56	56
IL12RB2	0.028	0.046	-10000	0	-0.051	89	89
GADD45G	-0.031	0.3	-10000	0	-0.73	58	58
natural killer cell activation	0.002	0.021	0.048	10	-0.036	69	79
RELB	0.04	0.009	-10000	0	0	27	27
RELA	0.041	0.006	-10000	0	0	10	10
IL18	0.03	0.025	-10000	0	-0.042	20	20
IL2RA	0.039	0.011	-10000	0	0	45	45
IFNG	0.037	0.013	-10000	0	0	60	60
STAT3 (dimer)	-0.027	0.29	-10000	0	-0.63	71	71
HLA-DRB5	0.02	0.028	-10000	0	-0.008	262	262
FASLG	-0.026	0.28	0.53	1	-0.77	42	43
NF kappa B2 p52/RelB	-0.015	0.29	-10000	0	-0.67	60	60
CD4	0.025	0.028	-10000	0	-0.012	189	189
SOCS1	0.038	0.012	-10000	0	0	50	50
EntrezGene:6955	-0.001	0.01	-10000	0	-0.026	59	59
CD3D	0.027	0.03	-10000	0	-0.039	65	65
CD3E	0.029	0.029	-10000	0	-0.037	67	67
CD3G	0.026	0.029	-10000	0	-0.04	57	57
IL12Rbeta2/JAK2	0.033	0.073	-10000	0	-0.15	27	27
CCL3	-0.046	0.33	-10000	0	-0.87	53	53
CCL4	-0.029	0.28	0.41	1	-0.66	60	61
HLA-A	0.038	0.014	-10000	0	-10000	0	0
IL18/IL18R	0.061	0.082	-10000	0	-0.11	82	82
NOS2	-0.027	0.27	0.4	1	-0.59	71	72
IL12/IL12R/TYK2/JAK2/SPHK2	0.031	0.1	0.21	17	-0.25	25	42
IL1R1	-0.11	0.43	-10000	0	-1	96	96
IL4	0.019	0.044	0.096	2	-0.061	18	20
JAK2	0.024	0.043	-10000	0	-0.052	79	79
EntrezGene:6957	-0.001	0.009	-10000	0	-0.023	42	42
TCR/CD3/MHC I/CD8	-0.012	0.12	-10000	0	-0.43	26	26
RAB7A	-0.032	0.28	-10000	0	-0.61	75	75
lysosomal transport	-0.028	0.26	0.39	1	-0.58	75	76
FOS	-0.19	0.52	-10000	0	-1.1	126	126
STAT4 (dimer)	-0.022	0.29	0.42	2	-0.66	66	68
STAT5A (dimer)	-0.024	0.28	-10000	0	-0.66	59	59
GZMA	-0.055	0.35	-10000	0	-0.96	52	52
GZMB	-0.037	0.32	0.56	1	-0.88	46	47
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.036	0.29	0.42	2	-0.7	59	61
TCR/CD3/MHC II/CD4	-0.069	0.21	-10000	0	-0.38	132	132
IL2/IL2R	0.047	0.082	-10000	0	-0.11	94	94
MAPK14	-0.049	0.33	-10000	0	-0.74	74	74
CCR5	-0.021	0.25	0.36	2	-0.55	71	73
IL1B	0.023	0.042	-10000	0	-0.052	66	66
STAT6	0.012	0.14	-10000	0	-0.56	12	12
STAT4	0.04	0.009	-10000	0	0	29	29
STAT3	0.038	0.013	-10000	0	0	56	56
STAT1	0.034	0.017	-10000	0	0	108	108
NFKB1	0.036	0.015	-10000	0	0	84	84
NFKB2	0.04	0.009	-10000	0	0	24	24
IL12B	0.027	0.046	-10000	0	-0.051	91	91
CD8A	0.043	0.005	-10000	0	-10000	0	0
CD8B	0.001	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.031	0.1	0.25	24	-0.21	18	42
IL2RB	0.036	0.014	-10000	0	0	75	75
proteasomal ubiquitin-dependent protein catabolic process	-0.015	0.28	0.42	2	-0.61	66	68
IL2RG	0.028	0.02	-10000	0	0	183	183
IL12	0.024	0.072	-10000	0	-0.15	33	33
STAT5A	0.038	0.012	-10000	0	0	51	51
CD247	-0.001	0.009	-10000	0	-0.023	43	43
IL2	0.039	0.012	-10000	0	0	46	46
SPHK2	0.04	0.009	-10000	0	0	25	25
FRAP1	0.04	0.009	-10000	0	0	27	27
IL12A	0.019	0.041	-10000	0	-0.052	66	66
IL12/IL12R/TYK2/JAK2	-0.045	0.3	-10000	0	-0.74	59	59
MAP2K3	-0.053	0.34	-10000	0	-0.78	72	72
RIPK2	0.033	0.017	-10000	0	0	125	125
MAP2K6	-0.056	0.32	-10000	0	-0.72	76	76
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.024	0.029	-10000	0	-0.011	206	206
IL18RAP	0.04	0.019	-10000	0	-0.042	24	24
IL12Rbeta1/TYK2	0.039	0.058	-10000	0	-0.087	5	5
EOMES	0.005	0.076	-10000	0	-0.52	9	9
STAT1 (dimer)	-0.043	0.29	-10000	0	-0.65	69	69
T cell proliferation	-0.021	0.24	0.38	2	-0.5	75	77
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.04	0.019	-10000	0	-0.042	23	23
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.03	0.25	-10000	0	-0.56	71	71
ATF2	-0.048	0.3	-10000	0	-0.68	76	76

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.039	0.011	-9999	0	38	38
ITGB7	0.039	0.011	-9999	0	40	40
ITGA4	0.035	0.015	-9999	0	88	88
alpha4/beta7 Integrin	0.033	0.065	-9999	-0.14	65	65
alpha4/beta1 Integrin	0.033	0.064	-9999	-0.14	64	64

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.035	0.048	-10000	0	-0.12	42	42
cell-cell adhesion	0.041	0.041	0.12	78	-10000	0	78
Ephrin B/EPHB2/RasGAP	0.053	0.096	-10000	0	-0.12	101	101
ITSN1	0.04	0.008	-10000	0	0	22	22
PIK3CA	0.03	0.019	-10000	0	0	155	155
SHC1	0.04	0.01	-10000	0	0	31	31
Ephrin B1/EPHB3	0.037	0.038	-10000	0	-0.11	22	22
Ephrin B1/EPHB1	0.048	0.024	-10000	0	-0.11	5	5
HRAS/GDP	-0.019	0.11	-10000	0	-0.18	130	130
Ephrin B/EPHB1/GRB7	0.058	0.089	-10000	0	-0.12	82	82
Endophilin/SYNJ1	-0.025	0.059	0.19	12	-0.2	6	18
KRAS	0.034	0.016	-10000	0	0	103	103
Ephrin B/EPHB1/Src	0.061	0.087	-10000	0	-0.12	77	77
endothelial cell migration	0.021	0.076	-10000	0	-0.12	99	99
GRB2	0.041	0.007	-10000	0	0	17	17
GRB7	0.037	0.013	-10000	0	0	63	63
PAK1	-0.018	0.071	0.18	29	-0.2	9	38
HRAS	0.04	0.01	-10000	0	0	31	31
RRAS	-0.025	0.058	0.19	9	-0.2	11	20
DNM1	0.039	0.011	-10000	0	0	38	38
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.011	0.071	0.19	34	-0.18	4	38
lamellipodium assembly	-0.041	0.041	-10000	0	-0.12	78	78
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.072	-10000	0	-0.15	70	70
PIK3R1	0.034	0.017	-10000	0	0	108	108
EPHB2	0.039	0.011	-10000	0	0	38	38
EPHB3	0.032	0.018	-10000	0	0	135	135
EPHB1	0.038	0.013	-10000	0	0	59	59
EPHB4	0.04	0.009	-10000	0	0	29	29
mol:GDP	-0.04	0.098	0.19	15	-0.23	70	85
Ephrin B/EPHB2	0.048	0.08	-10000	0	-0.11	96	96
Ephrin B/EPHB3	0.035	0.076	-10000	0	-0.11	88	88
JNK cascade	-0.003	0.1	0.28	51	-0.18	3	54
Ephrin B/EPHB1	0.049	0.075	-10000	0	-0.11	81	81
RAP1/GDP	-0.026	0.12	0.29	4	-0.22	81	85
EFNB2	0.031	0.018	-10000	0	0	143	143
EFNB3	0.037	0.014	-10000	0	0	71	71
EFNB1	0.041	0.007	-10000	0	0	16	16
Ephrin B2/EPHB1-2	0.036	0.067	-10000	0	-0.11	77	77
RAP1B	0.038	0.013	-10000	0	0	59	59
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.029	0.099	-10000	0	-0.16	84	84
Rap1/GTP	-0.045	0.05	0.054	13	-0.19	16	29
axon guidance	0.035	0.047	-10000	0	-0.12	42	42
MAPK3	-0.003	0.069	0.2	6	-0.21	13	19
MAPK1	-0.001	0.068	0.2	6	-0.21	13	19
Rac1/GDP	-0.03	0.11	0.26	7	-0.21	75	82
actin cytoskeleton reorganization	-0.051	0.06	-10000	0	-0.16	72	72
CDC42/GDP	-0.029	0.11	0.26	6	-0.22	77	83
PI3K	0.025	0.08	-10000	0	-0.12	99	99
EFNA5	0.034	0.016	-10000	0	0	103	103
Ephrin B2/EPHB4	0.023	0.061	-10000	0	-0.11	83	83
Ephrin B/EPHB2/Intersectin/N-WASP	-0.001	0.08	-10000	0	-0.16	98	98
CDC42	0.04	0.009	-10000	0	0	24	24
RAS family/GTP	-0.041	0.049	0.051	10	-0.19	14	24
PTK2	0.16	0.26	0.56	165	-10000	0	165
MAP4K4	-0.003	0.1	0.28	51	-0.19	3	54
SRC	0.039	0.01	-10000	0	0	36	36
KALRN	0.038	0.012	-10000	0	0	54	54
Intersectin/N-WASP	0.056	0.025	-10000	0	-0.14	6	6
neuron projection morphogenesis	-0.017	0.094	0.28	24	-0.21	14	38
MAP2K1	-0.001	0.066	0.21	2	-0.22	12	14
WASL	0.04	0.009	-10000	0	0	24	24
Ephrin B1/EPHB1-2/NCK1	0.076	0.065	-10000	0	-0.12	40	40
cell migration	-0.009	0.091	0.23	11	-0.24	21	32
NRAS	0.04	0.009	-10000	0	0	30	30
SYNJ1	-0.025	0.06	0.19	12	-0.2	6	18
PXN	0.041	0.007	-10000	0	0	14	14
TF	-0.029	0.054	0.17	11	-0.2	6	17
HRAS/GTP	0.033	0.081	-10000	0	-0.12	86	86
Ephrin B1/EPHB1-2	0.062	0.043	-10000	0	-0.11	18	18
cell adhesion mediated by integrin	0.009	0.064	0.17	12	-0.22	14	26
RAC1	0.039	0.01	-10000	0	0	34	34
mol:GTP	0.037	0.083	-10000	0	-0.12	93	93
RAC1-CDC42/GTP	-0.04	0.046	-10000	0	-0.19	10	10
RASA1	0.037	0.014	-10000	0	0	71	71
RAC1-CDC42/GDP	-0.018	0.11	0.27	6	-0.21	74	80
ruffle organization	-0.021	0.08	0.23	15	-0.24	2	17
NCK1	0.036	0.015	-10000	0	0	80	80
receptor internalization	-0.03	0.055	0.17	11	-0.19	8	19
Ephrin B/EPHB2/KALRN	0.059	0.092	-10000	0	-0.12	88	88
ROCK1	0.02	0.089	0.19	111	-10000	0	111
RAS family/GDP	-0.055	0.062	-10000	0	-0.16	107	107
Rac1/GTP	-0.039	0.046	0.051	4	-0.12	78	82
Ephrin B/EPHB1/Src/Paxillin	0.004	0.072	-10000	0	-0.15	78	78

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.014	0.15	0.24	19	-0.33	61	80
FYN	-0.029	0.18	0.23	18	-0.4	77	95
LAT/GRAP2/SLP76	-0.003	0.15	0.24	6	-0.33	69	75
IKBKB	0.039	0.011	-10000	0	0	44	44
AKT1	-0.014	0.14	0.21	13	-0.32	73	86
B2M	0.037	0.017	-10000	0	-0.003	76	76
IKBKG	-0.002	0.05	0.12	11	-0.11	46	57
MAP3K8	0.04	0.008	-10000	0	0	21	21
mol:Ca2+	-0.013	0.016	0.051	11	-0.042	45	56
integrin-mediated signaling pathway	0.045	0.035	-10000	0	-0.11	22	22
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.026	0.18	0.24	11	-0.43	74	85
TRPV6	0.087	0.34	1.3	43	-10000	0	43
CD28	0.041	0.007	-10000	0	0	16	16
SHC1	-0.01	0.16	0.22	24	-0.39	61	85
receptor internalization	-0.016	0.14	0.17	3	-0.34	72	75
PRF1	-0.009	0.21	-10000	0	-0.81	25	25
KRAS	0.034	0.016	-10000	0	0	103	103
GRB2	0.041	0.007	-10000	0	0	17	17
COT/AKT1	0.005	0.12	0.21	11	-0.26	70	81
LAT	-0.017	0.16	0.23	10	-0.38	64	74
EntrezGene:6955	0.001	0.003	-10000	0	-0.023	3	3
CD3D	0.034	0.018	-10000	0	-0.001	111	111
CD3E	0.037	0.016	-10000	0	-0.001	80	80
CD3G	0.032	0.02	-10000	0	-0.002	136	136
RASGRP2	0.008	0.019	-10000	0	-0.14	2	2
RASGRP1	-0.021	0.15	0.22	11	-0.32	80	91
HLA-A	0.038	0.015	-10000	0	-0.002	67	67
RASSF5	0.039	0.01	-10000	0	0	34	34
RAP1A/GTP/RAPL	0.046	0.035	-10000	0	-0.11	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.061	0.14	24	-0.11	43	67
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.019	0.065	-10000	0	-0.16	71	71
PRKCA	-0.008	0.083	0.17	19	-0.2	55	74
GRAP2	0.038	0.013	-10000	0	0	57	57
mol:IP3	-0.016	0.11	-10000	0	-0.27	66	66
EntrezGene:6957	0.001	0.004	-10000	0	-0.022	2	2
TCR/CD3/MHC I/CD8	-0.01	0.12	-10000	0	-0.36	45	45
ORAI1	-0.082	0.28	-10000	0	-1.1	43	43
CSK	-0.014	0.16	0.23	11	-0.39	61	72
B7 family/CD28	0.027	0.16	0.27	6	-0.36	63	69
CHUK	0.038	0.012	-10000	0	0	52	52
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.023	0.17	0.21	3	-0.4	70	73
PTPN6	-0.01	0.16	0.2	35	-0.36	66	101
VAV1	-0.018	0.16	0.21	12	-0.4	64	76
Monovalent TCR/CD3	-0.004	0.083	-10000	0	-0.21	65	65
CBL	0.04	0.008	-10000	0	0	23	23
LCK	-0.018	0.18	0.23	19	-0.4	70	89
PAG1	-0.009	0.16	0.21	33	-0.4	58	91
RAP1A	0.039	0.01	-10000	0	0	35	35
TCR/CD3/MHC I/CD8/LCK	-0.022	0.17	0.2	4	-0.37	79	83
CD80	0.04	0.01	-10000	0	0	35	35
CD86	0.035	0.016	-10000	0	0	102	102
PDK1/CARD11/BCL10/MALT1	-0.007	0.085	-10000	0	-0.2	66	66
HRAS	0.04	0.01	-10000	0	0	31	31
GO:0035030	-0.013	0.13	0.18	18	-0.3	68	86
CD8A	0.042	0.01	-10000	0	-0.015	15	15
CD8B	0.001	0.004	-10000	0	-0.022	4	4
PTPRC	0.025	0.021	-10000	0	0	228	228
PDK1/PKC theta	-0.021	0.16	0.25	9	-0.37	69	78
CSK/PAG1	-0.008	0.16	0.23	22	-0.39	57	79
SOS1	0.038	0.013	-10000	0	0	56	56
peptide-MHC class I	0.038	0.07	-10000	0	-0.18	45	45
GRAP2/SLP76	0.001	0.17	0.25	6	-0.38	71	77
STIM1	-0.022	0.075	1.1	1	-10000	0	1
RAS family/GTP	0.011	0.078	0.16	13	-0.16	51	64
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.018	0.15	0.17	3	-0.36	72	75
mol:DAG	-0.028	0.09	-10000	0	-0.24	70	70
RAP1A/GDP	0.011	0.033	0.073	17	-0.058	43	60
PLCG1	0.038	0.012	-10000	0	0	50	50
CD247	0.001	0.003	-10000	0	-0.023	3	3
cytotoxic T cell degranulation	-0.007	0.2	-10000	0	-0.76	26	26
RAP1A/GTP	0.003	0.011	-10000	0	-0.037	17	17
mol:PI-3-4-5-P3	-0.018	0.16	0.22	13	-0.36	74	87
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.011	0.14	0.22	1	-0.34	61	62
NRAS	0.04	0.009	-10000	0	0	30	30
ZAP70	0.041	0.006	-10000	0	0	10	10
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
LAT/GRAP2/SLP76/VAV1	-0.012	0.14	0.24	5	-0.35	64	69
MALT1	0.036	0.014	-10000	0	0	76	76
TRAF6	0.04	0.008	-10000	0	0	22	22
CD8 heterodimer	0.031	0.012	-10000	0	-0.038	7	7
CARD11	0.038	0.013	-10000	0	0	56	56
PRKCB	-0.028	0.062	-10000	0	-0.17	70	70
PRKCE	-0.005	0.085	0.17	22	-0.2	52	74
PRKCQ	-0.023	0.17	0.23	9	-0.4	71	80
LCP2	0.034	0.016	-10000	0	0	102	102
BCL10	0.041	0.006	-10000	0	0	11	11
regulation of survival gene product expression	-0.009	0.12	0.2	15	-0.27	73	88
IKK complex	0.004	0.05	0.13	22	-0.095	23	45
RAS family/GDP	-0.002	0.014	-10000	0	-0.035	40	40
MAP3K14	-0.002	0.094	0.16	15	-0.2	70	85
PDPK1	-0.015	0.13	0.21	15	-0.3	72	87
TCR/CD3/MHC I/CD8/Fyn	-0.037	0.2	-10000	0	-0.48	69	69

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.049	0.064	-9999	-0.13	48	48
E-cadherin/beta catenin	0.04	0.052	-9999	-0.14	36	36
CTNNB1	0.04	0.01	-9999	0	31	31
JUP	0.037	0.014	-9999	0	67	67
CDH1	0.035	0.016	-9999	0	98	98

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.001	0.068	0.14	13	-0.19	56	69
CRKL	0.039	0.011	-10000	0	0	38	38
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
DOCK1	0.037	0.013	-10000	0	0	62	62
ITGA4	0.035	0.015	-10000	0	0	88	88
alpha4/beta7 Integrin/MAdCAM1	0.067	0.074	-10000	0	-0.11	66	66
EPO	0.04	0.008	-10000	0	0	20	20
alpha4/beta7 Integrin	0.033	0.065	-10000	0	-0.14	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	52	52
alpha4/beta1 Integrin	0.033	0.064	-10000	0	-0.14	64	64
EPO/EPOR (dimer)	0.052	0.025	-10000	0	-0.14	2	2
lamellipodium assembly	0.017	0.11	0.21	1	-0.34	20	21
PIK3CA	0.03	0.019	-10000	0	0	155	155
PI3K	0.024	0.061	-10000	0	-0.15	47	47
ARF6	0.041	0.008	-10000	0	0	19	19
JAK2	0.007	0.067	-10000	0	-0.18	53	53
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.017	-10000	0	0	108	108
MADCAM1	0.037	0.013	-10000	0	0	64	64
cell adhesion	0.065	0.072	-10000	0	-0.11	66	66
CRKL/CBL	0.055	0.021	-10000	0	-0.14	1	1
ITGB1	0.039	0.011	-10000	0	0	38	38
SRC	-0.018	0.089	0.18	34	-0.19	40	74
ITGB7	0.039	0.011	-10000	0	0	40	40
RAC1	0.039	0.01	-10000	0	0	34	34
alpha4/beta1 Integrin/VCAM1	-0.005	0.096	-10000	0	-0.14	153	153
p130Cas/Crk/Dock1	0.012	0.098	0.23	17	-0.18	44	61
VCAM1	0.02	0.021	-10000	0	0	288	288
RHOA	0.041	0.007	-10000	0	0	14	14
alpha4/beta1 Integrin/Paxillin/GIT1	0.07	0.073	-10000	0	-0.11	63	63
BCAR1	-0.02	0.08	0.17	29	-0.18	40	69
EPOR	0.036	0.014	-10000	0	0	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.04	0.008	-10000	0	0	23	23
GIT1	0.04	0.009	-10000	0	0	27	27
Rac1/GTP	0.017	0.11	0.21	1	-0.36	20	21

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.025	0.06	0.2	3	-0.22	35	38
RFC1	-0.023	0.06	0.22	1	-0.22	35	36
PRKDC	-0.019	0.068	0.21	13	-0.21	38	51
RIPK1	0.038	0.012	-10000	0	0	48	48
CASP7	0.002	0.12	-10000	0	-0.57	20	20
FASLG/FAS/FADD/FAF1	0.022	0.082	0.15	103	-0.18	38	141
MAP2K4	0.002	0.12	0.32	4	-0.32	38	42
mol:ceramide	0.018	0.094	-10000	0	-0.29	23	23
GSN	-0.023	0.061	0.2	4	-0.22	37	41
FASLG/FAS/FADD/FAF1/Caspase 8	0.027	0.091	0.21	16	-0.25	18	34
FAS	0.035	0.018	-10000	0	-0.002	105	105
BID	-0.034	0.024	0.23	2	-0.13	12	14
MAP3K1	-0.001	0.11	0.25	7	-0.36	30	37
MAP3K7	0.039	0.012	-10000	0	0	47	47
RB1	-0.025	0.061	0.18	2	-0.22	35	37
CFLAR	0.04	0.008	-10000	0	0	21	21
HGF/MET	-0.014	0.092	-10000	0	-0.14	168	168
ARHGDIB	-0.012	0.074	0.23	23	-0.22	25	48
FADD	0.041	0.012	-10000	0	-0.01	28	28
actin filament polymerization	0.023	0.06	0.21	37	-0.2	4	41
NFKB1	-0.05	0.24	-10000	0	-0.64	72	72
MAPK8	-0.002	0.12	0.34	3	-0.36	32	35
DFFA	-0.021	0.064	0.2	7	-0.21	40	47
DNA fragmentation during apoptosis	-0.021	0.062	0.22	5	-0.21	38	43
FAS/FADD/MET	0.017	0.09	-10000	0	-0.13	129	129
CFLAR/RIP1	0.052	0.031	-10000	0	-0.15	8	8
FAIM3	0.04	0.009	-10000	0	0	26	26
FAF1	0.041	0.013	-10000	0	-0.009	33	33
PARP1	-0.02	0.067	0.22	13	-0.21	36	49
DFFB	-0.021	0.062	0.22	5	-0.21	38	43
CHUK	-0.058	0.22	-10000	0	-0.61	71	71
FASLG	0.041	0.013	-10000	0	-0.012	29	29
FAS/FADD	0.036	0.062	-10000	0	-0.14	56	56
HGF	0.04	0.009	-10000	0	0	29	29
LMNA	-0.019	0.068	0.19	17	-0.22	30	47
CASP6	-0.019	0.06	0.14	2	-0.24	26	28
CASP10	0.037	0.017	-10000	0	-0.004	75	75
CASP3	-0.022	0.064	0.16	4	-0.24	41	45
PTPN13	0.021	0.021	-10000	0	0	276	276
CASP8	-0.031	0.02	0.26	2	-10000	0	2
IL6	-0.043	0.24	-10000	0	-0.65	52	52
MET	0.027	0.02	-10000	0	0	198	198
ICAD/CAD	-0.024	0.061	0.19	11	-0.2	40	51
FASLG/FAS/FADD/FAF1/Caspase 10	0.018	0.095	-10000	0	-0.3	23	23
activation of caspase activity by cytochrome c	-0.034	0.024	0.23	2	-0.13	12	14
PAK2	-0.024	0.06	0.14	2	-0.22	39	41
BCL2	0.036	0.014	-10000	0	0	76	76

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.052	0.14	-10000	0	-0.34	72	72
IKBKB	0.017	0.099	0.26	11	-0.27	19	30
AKT1	0.024	0.093	0.23	44	-0.18	8	52
IKBKG	0.02	0.077	0.23	1	-0.27	9	10
CALM1	-0.012	0.12	0.2	7	-0.35	37	44
PIK3CA	0.03	0.019	-10000	0	0	155	155
MAP3K1	-0.045	0.16	-10000	0	-0.42	59	59
MAP3K7	0.038	0.012	-10000	0	0	47	47
mol:Ca2+	-0.011	0.12	0.21	4	-0.36	44	48
DOK1	0.04	0.009	-10000	0	0	24	24
AP-1	-0.027	0.096	-10000	0	-0.21	71	71
LYN	0.036	0.015	-10000	0	0	83	83
BLNK	0.037	0.014	-10000	0	0	70	70
SHC1	0.04	0.01	-10000	0	0	31	31
BCR complex	0.053	0.025	-10000	0	-0.13	3	3
CD22	-0.011	0.088	-10000	0	-0.27	37	37
CAMK2G	-0.015	0.11	0.2	14	-0.33	39	53
CSNK2A1	0.038	0.012	-10000	0	0	54	54
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.02	0.063	-10000	0	-0.13	59	59
GO:0007205	-0.013	0.13	0.21	4	-0.36	45	49
SYK	0.037	0.014	-10000	0	0	70	70
ELK1	-0.017	0.12	0.22	3	-0.35	43	46
NFATC1	-0.029	0.11	0.21	2	-0.29	49	51
B-cell antigen/BCR complex	0.053	0.025	-10000	0	-0.13	3	3
PAG1/CSK	0.053	0.027	-10000	0	-0.14	5	5
NFKBIB	0.012	0.066	0.13	1	-0.13	81	82
HRAS	-0.011	0.1	0.25	3	-0.28	41	44
NFKBIA	0.014	0.061	0.13	1	-0.12	71	72
NF-kappa-B/RelA/I kappa B beta	0.02	0.059	0.13	1	-0.1	72	73
RasGAP/Csk	0.057	0.088	-10000	0	-0.11	84	84
mol:GDP	-0.012	0.12	0.21	4	-0.35	46	50
PTEN	0.039	0.011	-10000	0	0	38	38
CD79B	0.04	0.008	-10000	0	0	19	19
NF-kappa-B/RelA/I kappa B alpha	0.022	0.055	0.13	2	-0.1	64	66
GRB2	0.041	0.007	-10000	0	0	17	17
PI3K/BCAP/CD19	-0.027	0.15	-10000	0	-0.41	44	44
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	-0.008	0.12	0.21	4	-0.36	43	47
CSK	0.04	0.008	-10000	0	0	21	21
FOS	-0.017	0.12	0.22	5	-0.33	48	53
CHUK	-0.002	0.11	0.23	1	-0.29	53	54
IBTK	0.037	0.014	-10000	0	0	66	66
CARD11/BCL10/MALT1/TAK1	0.013	0.13	-10000	0	-0.32	39	39
PTPN6	-0.003	0.09	0.18	24	-0.27	28	52
RELA	0.041	0.006	-10000	0	0	10	10
BCL2A1	0.014	0.044	0.11	3	-0.079	67	70
VAV2	-0.022	0.12	-10000	0	-0.32	52	52
ubiquitin-dependent protein catabolic process	0.015	0.065	-10000	0	-0.12	81	81
BTK	-0.037	0.25	-10000	0	-1.1	32	32
CD19	-0.019	0.095	-10000	0	-0.28	42	42
MAP4K1	0.039	0.012	-10000	0	0	46	46
CD72	0.04	0.008	-10000	0	0	20	20
PAG1	0.038	0.012	-10000	0	0	53	53
MAPK14	-0.038	0.14	0.26	3	-0.36	59	62
SH3BP5	0.04	0.008	-10000	0	0	23	23
PIK3AP1	-0.01	0.13	0.24	4	-0.39	36	40
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.02	0.17	-10000	0	-0.45	52	52
RAF1	-0.015	0.095	0.24	5	-0.28	38	43
RasGAP/p62DOK/SHIP	0.045	0.078	-10000	0	-0.11	88	88
CD79A	0.037	0.013	-10000	0	0	60	60
re-entry into mitotic cell cycle	-0.027	0.095	-10000	0	-0.21	66	66
RASA1	0.037	0.014	-10000	0	0	71	71
MAPK3	-0.02	0.085	0.23	6	-0.26	35	41
MAPK1	-0.018	0.083	0.22	7	-0.25	33	40
CD72/SHP1	0.025	0.12	0.28	21	-0.26	28	49
NFKB1	0.036	0.015	-10000	0	0	84	84
MAPK8	-0.043	0.14	-10000	0	-0.36	58	58
actin cytoskeleton organization	-0.024	0.11	0.25	3	-0.29	49	52
NF-kappa-B/RelA	0.033	0.12	0.24	1	-0.22	75	76
Calcineurin	0.012	0.12	-10000	0	-0.3	43	43
PI3K	-0.011	0.075	-10000	0	-0.25	20	20
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.001	0.12	0.23	4	-0.36	41	45
SOS1	0.038	0.013	-10000	0	0	56	56
Bam32/HPK1	-0.051	0.25	-10000	0	-0.68	63	63
DAPP1	-0.075	0.27	-10000	0	-0.76	63	63
cytokine secretion	-0.027	0.1	0.21	2	-0.27	49	51
mol:DAG	-0.008	0.12	0.21	4	-0.36	43	47
PLCG2	0.035	0.015	-10000	0	0	87	87
MAP2K1	-0.018	0.091	0.24	6	-0.27	36	42
B-cell antigen/BCR complex/FcgammaRIIB	0.037	0.071	-10000	0	-0.12	75	75
mol:PI-3-4-5-P3	0.011	0.094	0.22	38	-0.22	13	51
ETS1	-0.013	0.11	0.25	8	-0.32	40	48
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.069	0.083	-10000	0	-0.12	61	61
B-cell antigen/BCR complex/LYN	-0.013	0.1	-10000	0	-0.28	44	44
MALT1	0.036	0.014	-10000	0	0	76	76
TRAF6	0.04	0.008	-10000	0	0	22	22
RAC1	-0.024	0.11	0.25	3	-0.3	51	54
B-cell antigen/BCR complex/LYN/SYK	0.054	0.11	0.34	14	-0.24	16	30
CARD11	-0.013	0.12	0.22	7	-0.36	41	48
FCGR2B	0.03	0.019	-10000	0	0	164	164
PPP3CA	0.037	0.013	-10000	0	0	61	61
BCL10	0.041	0.006	-10000	0	0	11	11
IKK complex	0.018	0.052	0.15	18	-0.12	13	31
PTPRC	0.025	0.021	-10000	0	0	228	228
PDPK1	0.015	0.083	0.2	46	-0.17	9	55
PPP3CB	0.04	0.01	-10000	0	0	31	31
PPP3CC	0.033	0.017	-10000	0	0	117	117
POU2F2	0.014	0.042	0.12	2	-0.076	70	72

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.038	0.013	-10000	0	0	56	56
HDAC3	0.041	0.007	-10000	0	0	15	15
VDR	0.038	0.013	-10000	0	0	56	56
Cbp/p300/PCAF	0.04	0.044	-10000	0	-0.14	26	26
EP300	0.036	0.014	-10000	0	0	73	73
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.012	0.095	0.18	1	-0.26	47	48
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.04	0.009	-10000	0	0	28	28
AKT1	0.01	0.091	0.21	17	-0.21	26	43
RAR alpha/9cRA/Cyclin H	-0.002	0.12	-10000	0	-0.24	73	73
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.079	-10000	0	-0.21	52	52
CDC2	0.026	0.024	-10000	0	-0.005	199	199
response to UV	-0.001	0.008	-10000	0	-0.026	43	43
RAR alpha/Jnk1	0.017	0.068	-10000	0	-0.16	43	43
NCOR2	0.04	0.009	-10000	0	0	28	28
VDR/VDR/Vit D3	0.023	0.031	-10000	0	-0.13	22	22
RXRs/RARs/NRIP1/9cRA	-0.037	0.19	-10000	0	-0.51	60	60
NCOA2	0.037	0.014	-10000	0	0	71	71
NCOA3	0.036	0.015	-10000	0	0	83	83
NCOA1	0.04	0.009	-10000	0	0	28	28
VDR/VDR/DNA	0.038	0.013	-10000	0	0	56	56
RARG	0.036	0.021	-10000	0	-0.018	68	68
RAR gamma1/9cRA	0.042	0.033	-10000	0	-0.11	14	14
MAPK3	0.036	0.022	-10000	0	-0.026	59	59
MAPK1	0.039	0.012	-10000	0	0	46	46
MAPK8	0.035	0.024	-10000	0	-0.025	70	70
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.013	0.14	-10000	0	-0.32	74	74
RARA	0.007	0.054	-10000	0	-0.16	42	42
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.005	0.083	-10000	0	-0.22	52	52
PRKCA	0.031	0.031	-10000	0	-0.072	34	34
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.044	0.2	-10000	0	-0.55	60	60
RXRG	0.016	0.057	-10000	0	-0.2	29	29
RXRA	-0.027	0.097	-10000	0	-0.24	51	51
RXRB	0.013	0.059	-10000	0	-0.2	33	33
VDR/Vit D3/DNA	0.023	0.031	-10000	0	-0.13	22	22
RBP1	0.03	0.019	-10000	0	0	164	164
CRBP1/9-cic-RA	0.002	0.057	-10000	0	-0.13	89	89
RARB	0.032	0.026	-10000	0	-0.015	118	118
PRKCG	0.036	0.032	-10000	0	-0.071	44	44
MNAT1	0.04	0.008	-10000	0	0	22	22
RAR alpha/RXRs	-0.015	0.16	0.27	2	-0.36	74	76
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.01	0.13	0.23	1	-0.3	60	61
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.1	0.18	1	-0.26	47	48
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.043	0.2	-10000	0	-0.55	60	60
positive regulation of DNA binding	-0.009	0.11	-10000	0	-0.23	74	74
NRIP1	-0.079	0.32	-10000	0	-0.98	54	54
RXRs/RARs	-0.027	0.17	-10000	0	-0.42	63	63
RXRs/RXRs/DNA/9cRA	-0.03	0.13	-10000	0	-0.33	76	76
PRKACA	0.035	0.015	-10000	0	0	89	89
CDK7	0.035	0.016	-10000	0	0	98	98
TFIIH	0.06	0.054	-10000	0	-0.14	25	25
RAR alpha/9cRA	0.037	0.087	-10000	0	-0.23	19	19
CCNH	0.037	0.014	-10000	0	0	68	68
CREBBP	0.038	0.012	-10000	0	0	54	54
RAR gamma2/9cRA	0.044	0.061	-10000	0	-0.13	34	34

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.042	0.15	-10000	0	-0.34	100	100
KLHL20	-0.016	0.1	0.2	14	-0.23	51	65
CYFIP2	0.038	0.012	-10000	0	0	47	47
Rac1/GDP	-0.012	0.11	0.28	4	-0.26	44	48
ENAH	-0.038	0.14	-10000	0	-0.33	97	97
AP1M1	0.036	0.014	-10000	0	0	77	77
RAP1B	0.038	0.013	-10000	0	0	59	59
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.04	0.01	-10000	0	0	31	31
CDC42/GTP	0.003	0.079	0.16	4	-0.22	23	27
ABI1/Sra1/Nap1	-0.033	0.054	-10000	0	-0.16	64	64
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.068	0.068	-10000	0	-0.11	43	43
RAPGEF1	-0.035	0.13	0.28	3	-0.31	81	84
CTNND1	0.041	0.007	-10000	0	0	17	17
regulation of calcium-dependent cell-cell adhesion	-0.029	0.15	-10000	0	-0.34	102	102
CRK	-0.033	0.13	0.25	1	-0.33	79	80
E-cadherin/gamma catenin/alpha catenin	0.05	0.065	-10000	0	-0.14	42	42
alphaE/beta7 Integrin	0.05	0.038	-10000	0	-0.14	17	17
IQGAP1	0.037	0.014	-10000	0	0	69	69
NCKAP1	0.04	0.01	-10000	0	0	31	31
Rap1/GTP/I-afadin	0.043	0.066	-10000	0	-0.11	69	69
DLG1	-0.044	0.15	-10000	0	-0.34	103	103
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.033	0.048	-10000	0	-0.15	55	55
MLLT4	0.034	0.017	-10000	0	0	107	107
ARF6/GTP/NME1/Tiam1	0.045	0.062	-10000	0	-0.11	58	58
PI3K	-0.04	0.063	-10000	0	-0.21	40	40
ARF6	0.041	0.008	-10000	0	0	19	19
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.038	0.052	-10000	0	-0.15	30	30
TIAM1	0.037	0.014	-10000	0	0	72	72
E-cadherin(dimer)/Ca2+	0.062	0.072	-10000	0	-0.13	51	51
AKT1	-0.008	0.063	0.16	15	-0.16	16	31
PIK3R1	0.034	0.017	-10000	0	0	108	108
CDH1	0.035	0.016	-10000	0	0	98	98
RhoA/GDP	-0.013	0.11	0.22	5	-0.26	47	52
actin cytoskeleton organization	-0.01	0.077	0.16	15	-0.17	48	63
CDC42/GDP	-0.012	0.11	0.28	4	-0.26	45	49
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.002	0.073	-10000	0	-0.2	55	55
ITGB7	0.039	0.011	-10000	0	0	40	40
RAC1	0.039	0.01	-10000	0	0	34	34
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.067	0.078	-10000	0	-0.14	51	51
E-cadherin/Ca2+/beta catenin/alpha catenin	0.046	0.056	-10000	0	-0.11	48	48
mol:GDP	-0.031	0.11	0.28	4	-0.29	47	51
CDC42/GTP/IQGAP1	0.04	0.047	-10000	0	-0.11	42	42
JUP	0.037	0.014	-10000	0	0	67	67
p120 catenin/RhoA/GDP	-0.001	0.12	0.24	4	-0.27	45	49
RAC1/GTP/IQGAP1	0.038	0.046	-10000	0	-0.11	42	42
PIP5K1C/AP1M1	0.049	0.026	-10000	0	-0.14	1	1
RHOA	0.041	0.007	-10000	0	0	14	14
CDC42	0.04	0.009	-10000	0	0	24	24
CTNNA1	0.039	0.011	-10000	0	0	38	38
positive regulation of S phase of mitotic cell cycle	-0.016	0.059	0.12	5	-0.12	94	99
NME1	0.035	0.015	-10000	0	0	91	91
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.039	0.15	-10000	0	-0.35	92	92
regulation of cell-cell adhesion	-0.008	0.064	-10000	0	-0.18	27	27
WASF2	-0.007	0.043	0.11	13	-0.095	42	55
Rap1/GTP	0.002	0.087	0.2	9	-0.24	24	33
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.071	0.083	-10000	0	-0.12	48	48
CCND1	-0.02	0.072	0.14	5	-0.15	95	100
VAV2	-0.051	0.22	-10000	0	-0.62	49	49
RAP1/GDP	0	0.098	0.24	6	-0.27	26	32
adherens junction assembly	-0.039	0.14	-10000	0	-0.34	93	93
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.04	0.009	-10000	0	0	26	26
PIP5K1C	0.038	0.012	-10000	0	0	54	54
regulation of heterotypic cell-cell adhesion	0.045	0.076	0.22	5	-0.13	60	65
E-cadherin/beta catenin	0.007	0.042	0.15	1	-0.23	14	15
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.037	0.14	-10000	0	-0.33	92	92
PIK3CA	0.03	0.019	-10000	0	0	155	155
Rac1/GTP	-0.057	0.13	-10000	0	-0.36	61	61
E-cadherin/beta catenin/alpha catenin	0.052	0.066	-10000	0	-0.13	48	48
ITGAE	0.039	0.01	-10000	0	0	37	37
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.03	0.16	-10000	0	-0.34	102	102

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.007	0.051	-10000	0	-0.15	40	40
EPHB2	0.039	0.011	-10000	0	0	38	38
Syndecan-2/TACI	0.026	0.041	-10000	0	-0.11	39	39
LAMA1	0.034	0.017	-10000	0	0	108	108
Syndecan-2/alpha2 ITGB1	0.041	0.086	-10000	0	-0.12	81	81
HRAS	0.04	0.01	-10000	0	0	31	31
Syndecan-2/CASK	0.001	0.028	-10000	0	-0.099	40	40
ITGA5	0.038	0.013	-10000	0	0	58	58
BAX	0.02	0.064	-10000	0	-10000	0	0
EPB41	0.039	0.01	-10000	0	0	35	35
positive regulation of cell-cell adhesion	0.017	0.046	-10000	0	-0.098	67	67
LAMA3	0.031	0.018	-10000	0	0	147	147
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.033	0.017	-10000	0	0	114	114
Syndecan-2/MMP2	0.008	0.052	-10000	0	-0.16	40	40
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.035	0.057	-10000	0	-0.14	43	43
dendrite morphogenesis	0.025	0.043	-10000	0	-0.12	38	38
Syndecan-2/GM-CSF	0.027	0.041	-10000	0	-0.11	39	39
determination of left/right symmetry	0.01	0.007	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.024	0.041	-10000	0	-0.11	38	38
GNB2L1	0.041	0.005	-10000	0	0	7	7
MAPK3	0.009	0.074	0.2	63	-10000	0	63
MAPK1	0.01	0.074	0.2	63	-10000	0	63
Syndecan-2/RACK1	0.041	0.048	-10000	0	-0.096	44	44
NF1	0.034	0.016	-10000	0	0	101	101
FGFR/FGF/Syndecan-2	0.01	0.007	-10000	0	-10000	0	0
ITGA2	0.033	0.017	-10000	0	0	118	118
MAPK8	0	0.02	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.054	0.076	-10000	0	-0.11	51	51
Syndecan-2/Kininogen	0.022	0.039	-10000	0	-0.11	35	35
ITGB1	0.039	0.011	-10000	0	0	38	38
SRC	0.006	0.073	0.19	65	-0.17	1	66
Syndecan-2/CASK/Protein 4.1	0.023	0.038	-10000	0	-0.094	43	43
extracellular matrix organization	0.024	0.042	-10000	0	-0.11	36	36
actin cytoskeleton reorganization	0.007	0.051	-10000	0	-0.15	40	40
Syndecan-2/Caveolin-2/Ras	0.03	0.06	-10000	0	-0.11	64	64
Syndecan-2/Laminin alpha3	0.018	0.045	-10000	0	-0.13	34	34
Syndecan-2/RasGAP	0.063	0.069	-10000	0	-0.099	53	53
alpha5/beta1 Integrin	0.046	0.045	-10000	0	-0.14	27	27
PRKCD	0.038	0.013	-10000	0	0	56	56
Syndecan-2 dimer	0.025	0.043	-10000	0	-0.12	38	38
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.059	0.2	1	-0.11	5	6
RHOA	0.041	0.007	-10000	0	0	14	14
SDCBP	0.036	0.014	-10000	0	0	75	75
TNFRSF13B	0.039	0.011	-10000	0	0	42	42
RASA1	0.037	0.014	-10000	0	0	71	71
alpha2/beta1 Integrin	0.035	0.057	-10000	0	-0.14	43	43
Syndecan-2/Synbindin	0.021	0.043	-10000	0	-0.12	39	39
TGFB1	0.037	0.013	-10000	0	0	62	62
CASP3	0.004	0.07	0.2	51	-0.18	1	52
FN1	0.021	0.021	-10000	0	0	277	277
Syndecan-2/IL8	0.018	0.044	-10000	0	-0.12	37	37
SDC2	0.01	0.007	-10000	0	-10000	0	0
KNG1	0.034	0.017	-10000	0	0	109	109
Syndecan-2/Neurofibromin	0.023	0.042	-10000	0	-0.12	35	35
TRAPPC4	0.034	0.016	-10000	0	0	102	102
CSF2	0.04	0.009	-10000	0	0	25	25
Syndecan-2/TGFB1	0.024	0.042	-10000	0	-0.11	36	36
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.046	-10000	0	-0.098	67	67
Syndecan-2/Ezrin	0.024	0.038	-10000	0	-0.095	42	42
PRKACA	0	0.069	0.2	43	-0.18	3	46
angiogenesis	0.018	0.044	-10000	0	-0.12	37	37
MMP2	0.022	0.021	-10000	0	0	273	273
IL8	0.032	0.018	-10000	0	0	139	139
calcineurin-NFAT signaling pathway	0.025	0.041	-10000	0	-0.11	39	39

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	0.067	0.066	-10000	0	-0.11	55	55
ER alpha/Gai/GDP/Gbeta gamma	-0.023	0.13	-10000	0	-0.32	63	63
AKT1	-0.09	0.27	-10000	0	-0.66	94	94
PIK3CA	0.03	0.019	-10000	0	0	155	155
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.089	0.28	-10000	0	-0.67	95	95
mol:Ca2+	-0.003	0.07	0.2	1	-0.28	21	22
IGF1R	0.033	0.017	-10000	0	0	118	118
E2/ER alpha (dimer)/Striatin	0.035	0.051	-10000	0	-0.11	52	52
SHC1	0.04	0.01	-10000	0	0	31	31
apoptosis	0.086	0.26	0.63	95	-10000	0	95
RhoA/GTP	0.014	0.049	-10000	0	-0.11	59	59
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.006	0.14	-10000	0	-0.29	73	73
regulation of stress fiber formation	0.014	0.072	0.16	15	-0.19	20	35
E2/ERA-ERB (dimer)	0.037	0.047	-10000	0	-0.11	44	44
KRAS	0.034	0.016	-10000	0	0	103	103
G13/GTP	0.033	0.046	-10000	0	-0.1	53	53
pseudopodium formation	-0.014	0.072	0.19	20	-0.16	15	35
E2/ER alpha (dimer)/PELP1	0.036	0.047	-10000	0	-0.11	44	44
GRB2	0.041	0.007	-10000	0	0	17	17
GNG2	0.039	0.01	-10000	0	0	34	34
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.04	0.01	-10000	0	0	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.038	0.16	-10000	0	-0.38	80	80
E2/ER beta (dimer)	0.03	0.005	-10000	0	-10000	0	0
mol:GDP	-0.005	0.079	0.14	3	-0.22	55	58
mol:NADP	-0.038	0.16	-10000	0	-0.38	80	80
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	-0.001	0.067	-10000	0	-0.29	21	21
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	118	118
PLCB1	0.005	0.064	-10000	0	-0.3	20	20
PLCB2	0.007	0.062	-10000	0	-0.28	21	21
IGF1	0.036	0.015	-10000	0	0	84	84
mol:L-citrulline	-0.038	0.16	-10000	0	-0.38	80	80
RHOA	0.041	0.007	-10000	0	0	14	14
Gai/GDP	-0.02	0.2	-10000	0	-0.59	58	58
JNK cascade	0.03	0.005	-10000	0	-10000	0	0
BCAR1	0.036	0.014	-10000	0	0	76	76
ESR2	0.041	0.007	-10000	0	0	18	18
GNAQ	0.038	0.012	-10000	0	0	49	49
ESR1	0.035	0.016	-10000	0	0	92	92
Gq family/GDP/Gbeta gamma	-0.037	0.22	-10000	0	-0.62	67	67
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.021	0.11	-10000	0	-0.64	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.006	0.14	0.24	1	-0.29	71	72
GNAZ	0.039	0.011	-10000	0	0	42	42
E2/ER alpha (dimer)	0.016	0.043	-10000	0	-0.13	44	44
STRN	0.04	0.009	-10000	0	0	30	30
GNAL	0.04	0.009	-10000	0	0	26	26
PELP1	0.039	0.01	-10000	0	0	36	36
MAPK11	0.013	0.008	0.069	1	-10000	0	1
GNAI2	0.041	0.007	-10000	0	0	15	15
GNAI3	0.039	0.011	-10000	0	0	45	45
GNAI1	0.035	0.016	-10000	0	0	95	95
HBEGF	-0.015	0.14	0.31	17	-0.33	50	67
cAMP biosynthetic process	0.032	0.039	-10000	0	-0.092	41	41
SRC	-0.022	0.13	0.22	19	-0.33	50	69
PI3K	0.024	0.061	-10000	0	-0.15	47	47
GNB1	0.041	0.005	-10000	0	0	7	7
G13/GDP/Gbeta gamma	0.04	0.095	-10000	0	-0.2	56	56
SOS1	0.038	0.013	-10000	0	0	56	56
IGF-1R heterotetramer/IGF1	-0.038	0.1	-10000	0	-0.25	70	70
Gs family/GTP	0.041	0.044	-10000	0	-0.093	41	41
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.054	0.05	-10000	0	-0.11	29	29
vasodilation	-0.036	0.16	-10000	0	-0.37	80	80
mol:DAG	-0.001	0.067	-10000	0	-0.29	21	21
Gs family/GDP/Gbeta gamma	0.003	0.081	-10000	0	-0.21	51	51
MSN	-0.017	0.073	0.17	39	-0.17	15	54
Gq family/GTP	0.019	0.067	-10000	0	-0.28	21	21
mol:PI-3-4-5-P3	-0.085	0.27	-10000	0	-0.63	102	102
NRAS	0.04	0.009	-10000	0	0	30	30
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.036	0.16	0.37	80	-10000	0	80
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
RhoA/GDP	0.014	0.09	-10000	0	-0.22	55	55
NOS3	-0.041	0.17	-10000	0	-0.4	80	80
GNA11	0.037	0.013	-10000	0	0	61	61
MAPKKK cascade	-0.028	0.19	-10000	0	-0.47	77	77
E2/ER alpha (dimer)/PELP1/Src	-0.011	0.14	0.24	4	-0.29	77	81
ruffle organization	-0.014	0.072	0.19	20	-0.16	15	35
ROCK2	-0.008	0.083	0.22	22	-0.17	8	30
GNA14	0.039	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GNA13	0.04	0.009	-10000	0	0	28	28
MMP9	-0.015	0.15	0.35	20	-0.32	52	72
MMP2	-0.019	0.13	0.24	5	-0.34	43	48

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.015	0.16	-10000	0	-0.44	55	55
HDAC1	0.043	0.025	0.083	115	-0.003	61	176
AES	0.039	0.016	0.08	17	0	68	85
FBXW11	0.04	0.009	-10000	0	0	25	25
DTX1	0.041	0.005	-10000	0	0	8	8
LRP6/FZD1	0.041	0.049	-10000	0	-0.14	32	32
TLE1	0.04	0.015	0.077	15	-0.001	52	67
AP1	-0.005	0.083	0.15	1	-0.18	91	92
NCSTN	0.04	0.008	-10000	0	0	24	24
ADAM10	0.039	0.011	-10000	0	0	45	45
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.071	0.22	-10000	0	-0.59	60	60
NICD/RBPSUH	-0.013	0.15	-10000	0	-0.44	55	55
WIF1	0.04	0.01	-10000	0	0	31	31
NOTCH1	-0.004	0.15	-10000	0	-0.46	52	52
PSENEN	0.035	0.016	-10000	0	0	92	92
KREMEN2	0.04	0.009	-10000	0	0	27	27
DKK1	0.039	0.011	-10000	0	0	44	44
beta catenin/beta TrCP1	0.018	0.091	0.25	2	-0.34	12	14
APH1B	0.036	0.015	-10000	0	0	83	83
APH1A	0.041	0.006	-10000	0	0	10	10
AXIN1	0.002	0.067	-10000	0	-0.41	4	4
CtBP/CBP/TCF1/TLE1/AES	0.013	0.099	0.18	86	-0.18	53	139
PSEN1	0.039	0.01	-10000	0	0	35	35
FOS	0.026	0.02	-10000	0	0	207	207
JUN	0.036	0.015	-10000	0	0	80	80
MAP3K7	0.041	0.015	0.069	15	0	47	62
CTNNB1	0.001	0.085	0.23	3	-0.34	12	15
MAPK3	0.041	0.007	-10000	0	0	17	17
DKK2/LRP6/Kremen 2	0.056	0.054	-10000	0	-0.12	29	29
HNF1A	0.002	0.008	0.037	19	-10000	0	19
CTBP1	0.04	0.015	0.08	19	0	56	75
MYC	-0.16	0.42	-10000	0	-1.2	76	76
NKD1	0.039	0.012	-10000	0	0	49	49
FZD1	0.041	0.007	-10000	0	0	17	17
NOTCH1 precursor/Deltex homolog 1	0.013	0.16	-10000	0	-0.44	55	55
apoptosis	-0.005	0.082	0.15	1	-0.17	91	92
Delta 1/NOTCHprecursor	0.01	0.16	-10000	0	-0.44	55	55
DLL1	0.038	0.012	-10000	0	0	52	52
PPARD	0.008	0.076	-10000	0	-1	2	2
Gamma Secretase	0.072	0.086	-10000	0	-0.12	66	66
APC	-0.021	0.12	-10000	0	-0.42	34	34
DVL1	0.018	0.058	-10000	0	-0.27	16	16
CSNK2A1	0.037	0.012	-10000	0	0	54	54
MAP3K7IP1	0.041	0.016	0.068	16	0	54	70
DKK1/LRP6/Kremen 2	0.055	0.053	-10000	0	-0.12	28	28
LRP6	0.034	0.016	-10000	0	0	107	107
CSNK1A1	0.039	0.009	-10000	0	0	26	26
NLK	0.027	0.043	-10000	0	-0.22	12	12
CCND1	-0.15	0.44	-10000	0	-1.2	82	82
WNT1	0.041	0.006	-10000	0	0	13	13
Axin1/APC/beta catenin	0.003	0.11	0.27	2	-0.36	19	21
DKK2	0.038	0.012	-10000	0	0	47	47
NOTCH1 precursor/DVL1	0.015	0.15	-10000	0	-0.39	52	52
GSK3B	0.041	0.009	-10000	0	0	26	26
FRAT1	0.041	0.009	-10000	0	0	24	24
NOTCH/Deltex homolog 1	0.019	0.16	-10000	0	-0.45	55	55
PPP2R5D	0.021	0.053	-10000	0	-0.29	11	11
MAPK1	0.039	0.012	-10000	0	0	46	46
WNT1/LRP6/FZD1	0.075	0.061	-10000	0	-0.11	31	31
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.03	0.024	-10000	0	-0.01	137	137

×

Class I PI3K signaling events

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
ARF5/GTP	-0.012	0.073	0.15	79	-0.18	6	85
DAPP1	-0.006	0.1	0.2	11	-0.26	39	50
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.011	0.14	-10000	0	-0.34	51	51
mol:DAG	0.006	0.076	0.18	20	-0.18	22	42
HRAS	0.041	0.014	0.079	3	-0.005	36	39
RAP1A	0.041	0.012	0.07	3	-0.001	36	39
ARF5/GDP	0.017	0.096	-10000	0	-0.24	34	34
PLCG2	0.035	0.015	-10000	0	0	87	87
PLCG1	0.038	0.012	-10000	0	0	50	50
ARF5	0.039	0.011	-10000	0	0	44	44
mol:GTP	-0.012	0.067	0.14	80	-0.18	5	85
ARF1/GTP	0.001	0.064	0.14	85	-0.17	5	90
RHOA	0.041	0.007	-10000	0	0	14	14
YES1	0.038	0.013	-10000	0	0	57	57
RAP1A/GTP	-0.008	0.076	0.16	80	-0.18	5	85
ADAP1	-0.014	0.061	0.13	74	-0.18	5	79
ARAP3	-0.012	0.066	0.14	80	-0.18	5	85
INPPL1	0.04	0.009	-10000	0	0	30	30
PREX1	0.037	0.013	-10000	0	0	64	64
ARHGEF6	0.037	0.013	-10000	0	0	65	65
ARHGEF7	0.04	0.009	-10000	0	0	27	27
ARF1	0.038	0.012	-10000	0	0	50	50
NRAS	0.042	0.011	0.069	3	0	30	33
FYN	0.034	0.016	-10000	0	0	103	103
ARF6	0.041	0.008	-10000	0	0	19	19
FGR	0.041	0.007	-10000	0	0	17	17
mol:Ca2+	0.002	0.05	0.19	13	-0.12	4	17
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.037	0.014	-10000	0	0	72	72
ZAP70	0.041	0.006	-10000	0	0	10	10
mol:IP3	-0.002	0.062	0.23	12	-0.16	8	20
LYN	0.036	0.015	-10000	0	0	83	83
ARF1/GDP	0.018	0.096	-10000	0	-0.25	33	33
RhoA/GDP	0.036	0.083	0.19	47	-0.18	18	65
PDK1/Src/Hsp90	0.05	0.021	-10000	0	-0.11	3	3
BLNK	0.037	0.014	-10000	0	0	70	70
actin cytoskeleton reorganization	0.009	0.093	0.23	17	-0.27	18	35
SRC	0.039	0.01	-10000	0	0	36	36
PLEKHA2	-0.014	0.006	-10000	0	-10000	0	0
RAC1	0.039	0.01	-10000	0	0	34	34
PTEN	0.031	0.028	-10000	0	-0.03	80	80
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.011	0.075	0.15	84	-0.18	5	89
RhoA/GTP	-0.01	0.079	0.16	86	-0.18	6	92
Src family/SYK family/BLNK-LAT	0	0.098	0.18	6	-0.28	33	39
BLK	0.033	0.017	-10000	0	0	117	117
PDPK1	0.04	0.009	-10000	0	0	25	25
CYTH1	-0.014	0.061	0.13	74	-0.18	5	79
HCK	0.036	0.015	-10000	0	0	80	80
CYTH3	-0.014	0.061	0.13	74	-0.18	5	79
CYTH2	-0.014	0.061	0.13	74	-0.18	5	79
KRAS	0.034	0.018	0.091	1	-0.001	107	108
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.011	0.043	0.16	2	-0.16	7	9
SGK1	0.011	0.041	-10000	0	-0.16	8	8
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.093	0.18	1	-0.26	36	37
SOS1	0.038	0.013	-10000	0	0	56	56
SYK	0.037	0.014	-10000	0	0	70	70
ARF6/GDP	0.002	0.079	0.17	56	-0.17	16	72
mol:PI-3-4-5-P3	-0.014	0.065	0.14	74	-0.18	5	79
ARAP3/RAP1A/GTP	-0.008	0.076	0.16	80	-0.18	5	85
VAV1	0.037	0.014	-10000	0	0	68	68
mol:PI-3-4-P2	-0.01	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.044	0.066	0.22	29	-0.12	39	68
PLEKHA1	-0.015	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.099	-10000	0	-0.25	35	35
LAT	0.041	0.006	-10000	0	0	13	13
Rac1/GTP	-0.004	0.1	-10000	0	-0.27	47	47
ITK	-0.014	0.065	0.13	76	-0.18	6	82
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0	0.092	0.22	14	-0.23	28	42
LCK	0.04	0.009	-10000	0	0	29	29
BTK	-0.015	0.068	0.13	76	-0.2	9	85

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.028	0.2	-10000	0	-0.72	37	37
epithelial cell differentiation	-0.027	0.19	-10000	0	-0.67	37	37
ITCH	0.039	0.037	0.1	8	-0.099	26	34
WWP1	-0.064	0.27	-10000	0	-1.1	33	33
FYN	0.034	0.016	-10000	0	0	103	103
EGFR	0.037	0.014	-10000	0	0	72	72
PRL	0.039	0.011	-10000	0	0	39	39
neuron projection morphogenesis	-0.043	0.16	0.25	9	-0.57	35	44
PTPRZ1	0.039	0.01	-10000	0	0	36	36
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.004	0.18	0.29	1	-0.61	36	37
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.034	0.18	-10000	0	-0.65	38	38
ADAM17	0.038	0.035	0.11	4	-0.082	28	32
ErbB4/ErbB4	-0.05	0.21	-10000	0	-0.79	36	36
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.03	0.2	-10000	0	-0.71	37	37
NCOR1	0.037	0.013	-10000	0	0	61	61
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.027	0.18	-10000	0	-0.58	42	42
GRIN2B	-0.035	0.16	0.25	4	-0.56	40	44
ErbB4/ErbB2/betacellulin	-0.028	0.18	-10000	0	-0.64	38	38
STAT1	0.034	0.017	-10000	0	0	108	108
HBEGF	0.04	0.01	-10000	0	0	32	32
PRLR	0.035	0.015	-10000	0	0	88	88
E4ICDs/ETO2	-0.031	0.2	-10000	0	-0.72	37	37
axon guidance	-0.056	0.23	-10000	0	-0.82	39	39
NEDD4	0.038	0.039	0.11	8	-0.084	38	46
Prolactin receptor/Prolactin receptor/Prolactin	0.049	0.025	-10000	0	-10000	0	0
CBFA2T3	0.036	0.015	-10000	0	0	81	81
ErbB4/ErbB2/HBEGF	-0.022	0.18	-10000	0	-0.63	38	38
MAPK3	-0.023	0.16	0.27	7	-0.58	35	42
STAT1 (dimer)	-0.034	0.21	-10000	0	-0.72	38	38
MAPK1	-0.024	0.16	0.27	7	-0.59	35	42
JAK2	0.035	0.016	-10000	0	0	92	92
ErbB4/ErbB2/neuregulin 1 beta	-0.033	0.17	-10000	0	-0.64	37	37
NRG1	-0.008	0.032	0.035	109	-0.11	20	129
NRG3	0.035	0.016	-10000	0	0	92	92
NRG2	0.041	0.007	-10000	0	0	14	14
NRG4	0.029	0.019	-10000	0	0	171	171
heart development	-0.056	0.23	-10000	0	-0.82	39	39
neural crest cell migration	-0.032	0.17	-10000	0	-0.63	37	37
ERBB2	-0.008	0.033	0.036	121	-0.1	24	145
WWOX/E4ICDs	-0.03	0.2	-10000	0	-0.72	37	37
SHC1	0.04	0.01	-10000	0	0	31	31
ErbB4/EGFR/neuregulin 4	-0.037	0.2	-10000	0	-0.7	37	37
apoptosis	0.031	0.19	0.62	44	-10000	0	44
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.026	0.2	-10000	0	-0.72	37	37
ErbB4/ErbB2/epiregulin	-0.02	0.18	-10000	0	-0.63	38	38
ErbB4/ErbB4/betacellulin/betacellulin	-0.035	0.2	-10000	0	-0.73	37	37
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.005	0.2	-10000	0	-0.64	36	36
MDM2	-0.042	0.19	0.28	9	-0.77	30	39
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.02	0.16	-10000	0	-0.57	38	38
STAT5A	-0.057	0.22	-10000	0	-0.8	38	38
ErbB4/EGFR/neuregulin 1 beta	-0.027	0.18	-10000	0	-0.62	38	38
DLG4	0.039	0.01	-10000	0	0	34	34
GRB2/SHC	0.056	0.024	-10000	0	-0.14	5	5
E4ICDs/TAB2/NCoR1	-0.02	0.2	-10000	0	-0.7	38	38
STAT5A (dimer)	-0.022	0.22	-10000	0	-0.75	37	37
MAP3K7IP2	0.038	0.013	-10000	0	0	59	59
STAT5B (dimer)	-0.038	0.23	-10000	0	-0.81	38	38
LRIG1	0.033	0.017	-10000	0	0	119	119
EREG	0.039	0.011	-10000	0	0	45	45
BTC	0.034	0.017	-10000	0	0	111	111
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.06	0.23	-10000	0	-0.83	39	39
ERBB4	-0.048	0.2	-10000	0	-0.84	32	32
STAT5B	0.039	0.011	-10000	0	0	43	43
YAP1	0.007	0.1	-10000	0	-0.52	17	17
GRB2	0.041	0.007	-10000	0	0	17	17
ErbB4/ErbB2/neuregulin 4	-0.033	0.18	-10000	0	-0.64	38	38
glial cell differentiation	0.02	0.2	0.69	38	-10000	0	38
WWOX	0.037	0.014	-10000	0	0	71	71
cell proliferation	-0.07	0.21	0.28	1	-0.6	60	61

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.012	0.17	-10000	0	-0.78	16	16
UGCG	-0.008	0.15	-10000	0	-0.69	22	22
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.02	0.18	0.29	3	-0.38	74	77
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.006	0.15	-10000	0	-0.68	22	22
mol:DAG	-0.008	0.029	0.17	13	-10000	0	13
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.038	0.23	0.37	1	-0.5	78	79
FRAP1	-0.056	0.26	0.4	1	-0.59	77	78
FOXO3	-0.055	0.26	0.37	1	-0.53	94	95
AKT1	-0.064	0.28	-10000	0	-0.58	94	94
GAB2	0.03	0.02	-10000	0	-0.002	152	152
SMPD1	0	0.12	-10000	0	-0.59	19	19
SGMS1	-0.003	0.038	0.065	9	-0.078	79	88
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	-0.02	0.035	-10000	0	-0.12	52	52
CALM1	0.04	0.01	-10000	0	0	31	31
cell proliferation	0.003	0.18	0.24	16	-0.32	81	97
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.021	0.064	-10000	0	-0.14	54	54
RPS6KB1	-0.023	0.2	-10000	0	-0.83	29	29
mol:sphingomyelin	-0.008	0.029	0.17	13	-10000	0	13
natural killer cell activation	-0.001	0.004	-10000	0	-0.015	19	19
JAK3	0.035	0.022	-10000	0	-0.046	23	23
PIK3R1	0.031	0.023	-10000	0	-0.041	24	24
JAK1	0.037	0.02	-10000	0	-0.043	22	22
NFKB1	0.036	0.015	-10000	0	0	84	84
MYC	-0.035	0.35	0.42	10	-0.82	78	88
MYB	-0.041	0.29	-10000	0	-1.1	38	38
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.028	0.17	0.25	3	-0.36	90	93
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.005	0.19	-10000	0	-0.77	29	29
mol:PI-3-4-5-P3	-0.025	0.17	0.27	4	-0.35	90	94
Rac1/GDP	0.008	0.045	-10000	0	-0.11	48	48
T cell proliferation	-0.029	0.16	0.25	5	-0.34	88	93
SHC1	0.037	0.016	-10000	0	-0.011	48	48
RAC1	0.039	0.01	-10000	0	0	34	34
positive regulation of cyclin-dependent protein kinase activity	0.002	0.02	0.032	46	-0.064	38	84
PRKCZ	-0.031	0.17	0.25	5	-0.35	89	94
NF kappa B1 p50/RelA	-0.03	0.24	0.4	1	-0.5	80	81
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.003	0.12	-10000	0	-0.34	40	40
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
IL2RA	0.036	0.017	-10000	0	-0.009	63	63
IL2RB	0.034	0.022	-10000	0	-0.045	22	22
TERT	0.037	0.014	-10000	0	0	68	68
E2F1	-0.001	0.12	-10000	0	-0.41	40	40
SOS1	0.035	0.018	-10000	0	-0.008	73	73
RPS6	0.039	0.011	-10000	0	0	41	41
mol:cAMP	-0.001	0.01	0.032	35	-0.017	46	81
PTPN11	0.036	0.02	-10000	0	-0.018	62	62
IL2RG	0.026	0.026	-10000	0	-0.042	27	27
actin cytoskeleton organization	-0.029	0.16	0.25	5	-0.34	88	93
GRB2	0.038	0.015	-10000	0	-0.017	36	36
IL2	0.035	0.023	-10000	0	-0.04	35	35
PIK3CA	0.028	0.024	-10000	0	-0.043	22	22
Rac1/GTP	0.031	0.062	-10000	0	-0.11	46	46
LCK	0.036	0.023	-10000	0	-0.04	36	36
BCL2	-0.032	0.2	0.4	1	-0.56	43	44

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.037	0.013	-10000	0	0	64	64
Caspase 8 (4 units)	0.036	0.094	-10000	0	-0.24	28	28
NEF	0.003	0.005	-10000	0	-0.1	1	1
NFKBIA	0.026	0.042	0.085	6	-0.068	78	84
BIRC3	-0.058	0.1	0.2	4	-0.28	89	93
CYCS	-0.006	0.069	0.19	12	-0.25	19	31
RIPK1	0.038	0.012	-10000	0	0	48	48
CD247	0.003	0.005	-10000	0	-0.1	1	1
MAP2K7	-0.006	0.17	-10000	0	-0.55	36	36
protein ubiquitination	-0.001	0.098	0.22	7	-0.27	34	41
CRADD	0.041	0.006	-10000	0	0	13	13
DAXX	0.041	0.008	-10000	0	0	19	19
FAS	0.035	0.016	-10000	0	0	99	99
BID	0.001	0.063	0.16	2	-0.26	16	18
NF-kappa-B/RelA/I kappa B alpha	0.029	0.12	-10000	0	-0.18	120	120
TRADD	0.036	0.014	-10000	0	0	76	76
MAP3K5	0.037	0.014	-10000	0	0	69	69
CFLAR	0.04	0.008	-10000	0	0	21	21
FADD	0.04	0.008	-10000	0	0	21	21
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.029	0.12	-10000	0	-0.18	120	120
MAPK8	-0.01	0.16	-10000	0	-0.53	34	34
APAF1	0.04	0.01	-10000	0	0	32	32
TRAF1	0.04	0.008	-10000	0	0	22	22
TRAF2	0.04	0.009	-10000	0	0	29	29
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.067	-10000	0	-0.17	51	51
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.005	0.11	-10000	0	-0.32	36	36
CHUK	-0.002	0.1	0.24	6	-0.29	34	40
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.075	0.085	-10000	0	-0.13	60	60
TCRz/NEF	0.01	0.008	-10000	0	-0.17	1	1
TNF	0.04	0.009	-10000	0	0	26	26
FASLG	0.022	0.014	-10000	0	-0.3	1	1
NFKB1	0.027	0.041	0.085	6	-0.07	66	72
TNFR1A/BAG4/TNF-alpha	0.059	0.046	-10000	0	-0.12	15	15
CASP6	-0.045	0.23	-10000	0	-0.54	85	85
CASP7	-0.046	0.2	0.29	6	-0.4	112	118
RELA	0.027	0.044	0.081	6	-0.066	97	103
CASP2	0.038	0.012	-10000	0	0	51	51
CASP3	-0.056	0.2	0.29	6	-0.41	116	122
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
TNFR1A/BAG4	0.044	0.038	-10000	0	-0.13	14	14
CASP8	0.04	0.009	-10000	0	0	28	28
CASP9	0.04	0.009	-10000	0	0	26	26
MAP3K14	0.007	0.11	0.25	6	-0.31	31	37
APAF-1/Caspase 9	-0.028	0.11	0.19	1	-0.25	93	94
BCL2	-0.011	0.14	-10000	0	-0.49	32	32

×

Circadian rhythm 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
chromatin modification	-0.049	0.31	-10000	0	-1	49	49
CLOCK	0.032	0.032	-10000	0	-0.069	41	41
TIMELESS/CRY2	-0.051	0.31	-10000	0	-1	49	49
DEC1/BMAL1	0.044	0.047	-10000	0	-0.082	56	56
ATR	0.035	0.016	-10000	0	0	93	93
NR1D1	-0.016	0.12	-10000	0	-0.64	3	3
ARNTL	0.032	0.032	-10000	0	-0.068	43	43
TIMELESS	-0.081	0.32	-10000	0	-1.1	49	49
NPAS2	0.027	0.031	-10000	0	-0.068	38	38
CRY2	0.042	0.004	-10000	0	0	5	5
mol:CO	0.001	0.041	0.13	49	-10000	0	49
CHEK1	0.033	0.017	-10000	0	0	120	120
mol:HEME	-0.001	0.041	-10000	0	-0.13	49	49
PER1	0.039	0.011	-10000	0	0	42	42
BMAL/CLOCK/NPAS2	0.034	0.096	-10000	0	-0.14	112	112
BMAL1/CLOCK	-0.04	0.2	-10000	0	-0.59	51	51
S phase of mitotic cell cycle	-0.049	0.31	-10000	0	-1	49	49
TIMELESS/CHEK1/ATR	-0.052	0.32	-10000	0	-1.1	49	49
mol:NADPH	-0.001	0.041	-10000	0	-0.13	49	49
PER1/TIMELESS	-0.053	0.31	-10000	0	-1	49	49
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.04	0.009	-10000	0	0	26	26

×

HIF-2-alpha transcription factor network

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
MMP14	-0.054	0.3	-10000	0	-0.88	64	64
oxygen homeostasis	0.003	0.011	0.032	19	-0.024	4	23
TCEB2	0.04	0.008	-10000	0	0	23	23
TCEB1	0.038	0.012	-10000	0	0	50	50
VHL/Elongin B/Elongin C/HIF2A	0.04	0.13	0.29	9	-0.22	59	68
EPO	0.026	0.18	0.36	10	-0.36	36	46
FIH (dimer)	0.04	0.023	0.089	2	-0.035	34	36
APEX1	0.033	0.034	-10000	0	-0.038	42	42
SERPINE1	-0.008	0.16	0.36	8	-0.34	47	55
FLT1	-0.043	0.26	-10000	0	-0.7	70	70
ADORA2A	0.005	0.17	0.34	16	-0.34	39	55
germ cell development	0.008	0.18	0.36	15	-0.34	51	66
SLC11A2	0.011	0.19	0.35	12	-0.37	47	59
BHLHE40	0.012	0.18	0.33	19	-0.31	64	83
HIF1AN	0.04	0.023	0.089	2	-0.035	34	36
HIF2A/ARNT/SIRT1	0.04	0.16	0.32	9	-0.26	58	67
ETS1	0.043	0.025	0.12	1	-0.11	5	6
CITED2	0.014	0.15	-10000	0	-0.63	25	25
KDR	-0.035	0.25	-10000	0	-0.71	63	63
PGK1	0.012	0.19	0.36	15	-0.38	50	65
SIRT1	0.041	0.008	-10000	0	0	20	20
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.062	0.23	0.46	1	-0.39	40	41
EPAS1	0.005	0.11	0.22	16	-0.22	65	81
SP1	0.034	0.05	-10000	0	-0.11	56	56
ABCG2	0.012	0.18	0.35	13	-0.34	49	62
EFNA1	0.001	0.19	0.35	11	-0.38	57	68
FXN	0.006	0.17	0.34	16	-0.34	43	59
POU5F1	0.006	0.18	0.36	14	-0.36	51	65
neuron apoptosis	-0.061	0.22	0.38	40	-0.46	1	41
EP300	0.036	0.014	-10000	0	0	73	73
EGLN3	0.028	0.027	0.085	1	-0.035	22	23
EGLN2	0.04	0.023	0.091	2	-0.033	31	33
EGLN1	0.039	0.024	0.089	2	-0.035	33	35
VHL/Elongin B/Elongin C	0.069	0.039	-10000	0	-0.12	11	11
VHL	0.04	0.009	-10000	0	0	28	28
ARNT	0.035	0.033	-10000	0	-0.039	41	41
SLC2A1	-0.012	0.18	0.35	10	-0.35	65	75
TWIST1	0.005	0.17	0.33	20	-0.33	46	66
ELK1	0.047	0.013	-10000	0	-0.088	3	3
HIF2A/ARNT/Cbp/p300	0.04	0.16	0.35	6	-0.27	50	56
VEGFA	0.012	0.18	0.33	19	-0.31	64	83
CREBBP	0.038	0.012	-10000	0	0	54	54

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.008	0.039	-10000	0	-0.11	62	62
STMN1	-0.011	0.016	0.029	13	-10000	0	13
Aurora B/RasGAP/Survivin	0.045	0.075	-10000	0	-0.16	52	52
Chromosomal passenger complex/Cul3 protein complex	-0.006	0.092	-10000	0	-0.24	49	49
BIRC5	0.037	0.014	-10000	0	-0.002	63	63
DES	-0.047	0.28	-10000	0	-0.8	63	63
Aurora C/Aurora B/INCENP	0.063	0.048	-10000	0	-0.12	28	28
Aurora B/TACC1	0.036	0.04	-10000	0	-0.1	29	29
Aurora B/PP2A	0.044	0.05	-10000	0	-0.14	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.011	0.063	-10000	0	-0.16	78	78
mitotic metaphase/anaphase transition	0.002	0.006	0.013	111	-10000	0	111
NDC80	-0.004	0.01	0.02	12	-10000	0	12
Cul3 protein complex	0.05	0.06	-10000	0	-0.12	42	42
KIF2C	-0.058	0.19	-10000	0	-0.48	81	81
PEBP1	-0.001	0.003	-10000	0	-0.011	40	40
KIF20A	0.033	0.018	-10000	0	0	133	133
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.036	0.058	-10000	0	-0.14	45	45
SEPT1	0.041	0.007	-10000	0	0	16	16
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.041	0.2	0.25	1	-0.56	63	64
PSMA3	0.037	0.013	-10000	0	0	60	60
G2/M transition of mitotic cell cycle	-0.001	0.003	0.009	37	-0.008	20	57
H3F3B	0.002	0.057	-10000	0	-0.2	40	40
AURKB	0.038	0.016	-10000	0	0	81	81
AURKC	0.042	0.002	-10000	0	0	1	1
CDCA8	0.036	0.016	-10000	0	-0.005	69	69
cytokinesis	-0.032	0.18	0.18	2	-0.42	76	78
Aurora B/Septin1	-0.007	0.19	0.22	1	-0.38	87	88
AURKA	-0.001	0.003	0.009	37	-0.008	20	57
INCENP	0.039	0.016	-10000	0	-0.03	27	27
KLHL13	0.033	0.017	-10000	0	0	121	121
BUB1	0.037	0.015	-10000	0	0	78	78
hSgo1/Aurora B/Survivin	0.04	0.079	-10000	0	-0.15	63	63
EVI5	0.039	0.01	-10000	0	0	35	35
RhoA/GTP	0.002	0.17	-10000	0	-0.34	76	76
SGOL1	0.036	0.014	-10000	0	0	74	74
CENPA	-0.017	0.12	-10000	0	-0.29	62	62
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.032	0.066	-10000	0	-0.14	63	63
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.037	0.063	-10000	0	-0.14	55	55
RHOA	0.041	0.007	-10000	0	0	14	14
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	-0.024	0.14	-10000	0	-0.34	75	75
RASA1	0.037	0.014	-10000	0	0	71	71
KLHL9	0.039	0.011	-10000	0	0	42	42
mitotic prometaphase	-0.001	0.003	-10000	0	-0.011	40	40
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.066	-10000	0	-0.14	63	63
PPP1CC	0.039	0.01	-10000	0	0	36	36
Centraspindlin	-0.011	0.17	-10000	0	-0.37	77	77
RhoA/GDP	0.03	0.012	-10000	0	-0.13	3	3
NSUN2	-0.012	0.12	-10000	0	-0.33	67	67
MYLK	0.001	0.057	-10000	0	-0.2	41	41
KIF23	0.035	0.016	-10000	0	0	98	98
VIM	-0.01	0.016	0.034	12	-10000	0	12
RACGAP1	0.037	0.014	-10000	0	-0.004	54	54
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.028	0.12	-10000	0	-0.31	87	87
Chromosomal passenger complex	-0.035	0.15	-10000	0	-0.32	80	80
Chromosomal passenger complex/EVI5	0.067	0.098	-10000	0	-0.17	57	57
TACC1	0.035	0.016	-10000	0	0	93	93
PPP2R5D	0.04	0.009	-10000	0	0	29	29
CUL3	0.04	0.008	-10000	0	0	21	21
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.013	0.14	0.26	4	-0.37	38	42
ACTA1	0.006	0.087	0.22	15	-0.24	17	32
NUMA1	-0.016	0.14	0.26	5	-0.37	35	40
SPTAN1	-0.001	0.087	0.24	11	-0.26	14	25
LIMK1	0.002	0.086	0.23	12	-0.26	13	25
BIRC3	0.026	0.02	-10000	0	0	218	218
BIRC2	0.036	0.014	-10000	0	0	75	75
BAX	0.04	0.008	-10000	0	0	22	22
CASP10	-0.011	0.025	0.058	54	-10000	0	54
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.034	0.17	0.26	5	-0.39	67	72
DIABLO	0.037	0.013	-10000	0	0	63	63
apoptotic nuclear changes	-0.002	0.086	0.24	11	-0.25	14	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.041	0.006	-10000	0	0	13	13
GSN	-0.001	0.087	0.22	15	-0.25	16	31
MADD	0.041	0.006	-10000	0	0	11	11
TFAP2A	-0.031	0.21	-10000	0	-0.57	54	54
BID	0.007	0.035	0.13	23	-0.094	26	49
MAP3K1	-0.027	0.14	-10000	0	-0.38	68	68
TRADD	0.036	0.014	-10000	0	0	76	76
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.051	0.041	-10000	0	-0.15	19	19
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.009	0.11	0.24	45	-0.24	23	68
CASP9	0.04	0.009	-10000	0	0	26	26
DNA repair	-0.013	0.081	0.26	24	-0.18	12	36
neuron apoptosis	-0.037	0.2	-10000	0	-0.66	44	44
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.014	0.12	0.28	6	-0.35	24	30
APAF1	0.04	0.01	-10000	0	0	32	32
CASP6	-0.1	0.34	-10000	0	-0.85	91	91
TRAF2	0.04	0.009	-10000	0	0	29	29
ICAD/CAD	0	0.085	0.25	11	-0.25	11	22
CASP7	0.014	0.11	0.19	83	-0.27	25	108
KRT18	-0.016	0.15	-10000	0	-0.62	23	23
apoptosis	-0.042	0.16	0.27	8	-0.38	74	82
DFFA	0.003	0.084	0.22	13	-0.25	13	26
DFFB	0.004	0.088	0.24	15	-0.26	12	27
PARP1	0.013	0.081	0.18	12	-0.27	24	36
actin filament polymerization	0.002	0.085	0.26	11	-0.24	13	24
TNF	0.04	0.009	-10000	0	0	26	26
CYCS	0.001	0.07	0.14	20	-0.21	36	56
SATB1	-0.11	0.32	-10000	0	-0.81	91	91
SLK	-0.001	0.086	0.22	13	-0.25	16	29
p15 BID/BAX	0.032	0.05	0.16	3	-0.2	8	11
CASP2	0.005	0.089	0.24	20	-0.24	31	51
JNK cascade	0.026	0.14	0.37	68	-10000	0	68
CASP3	0.007	0.09	0.2	22	-0.24	17	39
LMNB2	-0.047	0.21	0.27	2	-0.46	82	84
RIPK1	0.038	0.012	-10000	0	0	48	48
CASP4	0.034	0.017	-10000	0	0	107	107
Mammalian IAPs/DIABLO	0.012	0.089	-10000	0	-0.13	132	132
negative regulation of DNA binding	-0.03	0.2	-10000	0	-0.56	54	54
stress fiber formation	-0.002	0.086	0.22	13	-0.25	16	29
GZMB	-0.016	0.009	0	133	-10000	0	133
CASP1	-0.012	0.07	-10000	0	-0.2	68	68
LMNB1	-0.048	0.2	0.27	5	-0.4	87	92
APP	-0.037	0.2	-10000	0	-0.67	44	44
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.01	0.002	0	28	-10000	0	28
VIM	-0.036	0.16	0.27	10	-0.38	79	89
LMNA	-0.017	0.15	0.26	5	-0.34	71	76
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.006	0.085	-10000	0	-0.24	36	36
LRDD	0.039	0.01	-10000	0	0	35	35
SREBF1	0.001	0.085	0.22	12	-0.25	14	26
APAF-1/Caspase 9	0.028	0.15	-10000	0	-0.64	20	20
nuclear fragmentation during apoptosis	-0.016	0.13	0.26	5	-0.36	35	40
CFL2	-0.003	0.086	0.25	13	-0.27	11	24
GAS2	0.005	0.089	0.23	20	-0.26	13	33
positive regulation of apoptosis	-0.041	0.18	0.25	6	-0.39	96	102
PRF1	0.037	0.013	-10000	0	0	61	61

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.014	0.006	-10000	0	-10000	0	0
ADCY5	-0.014	0.006	0	86	-10000	0	86
ADCY6	-0.015	0.005	0	55	-10000	0	55
ADCY7	-0.014	0.006	0	77	-10000	0	77
ADCY1	-0.015	0.005	-10000	0	-10000	0	0
ADCY2	-0.014	0.006	0	95	-10000	0	95
ADCY3	-0.015	0.005	0	52	-10000	0	52
ADCY8	-0.008	0.008	-10000	0	-10000	0	0
PRKCE	-0.01	0.003	0	36	-10000	0	36
ADCY9	-0.014	0.006	0	76	-10000	0	76
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.054	0.085	0.22	71	-0.2	4	75

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.046	0.041	-10000	0	-0.14	20	20
VLDLR	0.032	0.018	-10000	0	0	129	129
CRKL	0.039	0.011	-10000	0	0	38	38
LRPAP1	0.036	0.015	-10000	0	0	78	78
FYN	0.034	0.016	-10000	0	0	103	103
ITGA3	0.034	0.016	-10000	0	0	104	104
RELN/VLDLR/Fyn	0.032	0.067	-10000	0	-0.13	51	51
MAPK8IP1/MKK7/MAP3K11/JNK1	0.095	0.061	-10000	0	-0.11	17	17
AKT1	0	0.075	-10000	0	-0.17	60	60
MAP2K7	0.039	0.011	-10000	0	0	43	43
RAPGEF1	0.04	0.008	-10000	0	0	23	23
DAB1	0.04	0.009	-10000	0	0	27	27
RELN/LRP8/DAB1	0.059	0.039	-10000	0	-0.11	5	5
LRPAP1/LRP8	0.041	0.053	-10000	0	-0.14	36	36
RELN/LRP8/DAB1/Fyn	0.066	0.056	-10000	0	-0.1	32	32
DAB1/alpha3/beta1 Integrin	0.029	0.082	-10000	0	-0.12	84	84
long-term memory	0.073	0.071	0.22	7	-0.11	28	35
DAB1/LIS1	0.058	0.082	-10000	0	-0.11	54	54
DAB1/CRLK/C3G	0.046	0.073	-10000	0	-0.12	52	52
PIK3CA	0.03	0.019	-10000	0	0	155	155
DAB1/NCK2	0.064	0.083	-10000	0	-0.12	55	55
ARHGEF2	0.039	0.01	-10000	0	0	37	37
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.034	0.017	-10000	0	0	111	111
CDK5R1	0.04	0.009	-10000	0	0	30	30
RELN	0.034	0.017	-10000	0	0	110	110
PIK3R1	0.034	0.017	-10000	0	0	108	108
RELN/LRP8/Fyn	0.045	0.057	-10000	0	-0.12	32	32
GRIN2A/RELN/LRP8/DAB1/Fyn	0.076	0.069	-10000	0	-0.11	31	31
MAPK8	0.04	0.009	-10000	0	0	30	30
RELN/VLDLR/DAB1	0.042	0.054	-10000	0	-0.11	37	37
ITGB1	0.039	0.011	-10000	0	0	38	38
MAP1B	0	0.066	0.22	25	-0.2	5	30
RELN/LRP8	0.049	0.055	-10000	0	-0.12	28	28
GRIN2B/RELN/LRP8/DAB1/Fyn	0.077	0.068	-10000	0	-0.11	26	26
PI3K	0.024	0.061	-10000	0	-0.15	47	47
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.03	0.066	-10000	0	-0.14	69	69
RAP1A	-0.002	0.097	0.3	27	-0.18	2	29
PAFAH1B1	0.038	0.012	-10000	0	0	49	49
MAPK8IP1	0.04	0.009	-10000	0	0	30	30
CRLK/C3G	0.056	0.018	-10000	0	-10000	0	0
GRIN2B	0.037	0.014	-10000	0	0	71	71
NCK2	0.042	0.004	-10000	0	0	6	6
neuron differentiation	0.023	0.059	0.17	1	-0.22	9	10
neuron adhesion	-0.011	0.1	0.28	33	-0.25	1	34
LRP8	0.039	0.011	-10000	0	0	39	39
GSK3B	-0.005	0.076	0.18	8	-0.16	61	69
RELN/VLDLR/DAB1/Fyn	0.051	0.068	-10000	0	-0.12	50	50
MAP3K11	0.041	0.006	-10000	0	0	12	12
RELN/VLDLR/DAB1/P13K	-0.004	0.068	-10000	0	-0.16	64	64
CDK5	0.036	0.015	-10000	0	0	83	83
MAPT	-0.009	0.034	0.68	1	-10000	0	1
neuron migration	0.004	0.099	0.27	29	-0.24	16	45
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.022	0.057	0.17	1	-0.21	8	9
RELN/VLDLR	0.053	0.073	-10000	0	-0.11	58	58

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.022	0.012	-10000	0	-0.1	1	1
ARNO/beta Arrestin1-2	0.043	0.032	-10000	0	-0.089	9	9
EGFR	0.037	0.014	-10000	0	0	72	72
EPHA2	0.039	0.01	-10000	0	0	35	35
USP6	0.039	0.01	-10000	0	0	36	36
IQSEC1	0.041	0.007	-10000	0	0	14	14
EGFR/EGFR/EGF/EGF	0.041	0.051	-10000	0	-0.13	37	37
ARRB2	0.016	0.017	-10000	0	-0.2	3	3
mol:GTP	0.001	0.014	-10000	0	-0.06	12	12
ARRB1	0.038	0.012	-10000	0	0	49	49
FBXO8	0.037	0.014	-10000	0	0	68	68
TSHR	0.038	0.013	-10000	0	0	60	60
EGF	0.038	0.012	-10000	0	0	53	53
somatostatin receptor activity	0	0	0	5	-0.001	40	45
ARAP2	0	0	0	10	0	34	44
mol:GDP	0.013	0.071	0.15	2	-0.19	31	33
mol:PI-3-4-5-P3	0	0	0	7	0	36	43
ITGA2B	0.04	0.009	-10000	0	0	30	30
ARF6	0.041	0.008	-10000	0	0	19	19
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.077	-10000	0	-0.12	61	61
ADAP1	0	0	0	7	0	22	29
KIF13B	0.034	0.017	-10000	0	0	112	112
HGF/MET	0.013	0.075	-10000	0	-0.14	105	105
PXN	0.041	0.007	-10000	0	0	14	14
ARF6/GTP	0.015	0.082	0.19	5	-0.22	37	42
EGFR/EGFR/EGF/EGF/ARFGEP100	0.06	0.055	-10000	0	-0.12	35	35
ADRB2	0.041	0.006	-10000	0	0	13	13
receptor agonist activity	0	0	0	8	0	34	42
actin filament binding	0	0	0	3	0	40	43
SRC	0.039	0.01	-10000	0	0	36	36
ITGB3	0.033	0.017	-10000	0	0	121	121
GNAQ	0.038	0.012	-10000	0	0	49	49
EFA6/PI-4-5-P2	0	0	0.001	11	-0.001	26	37
ARF6/GDP	0.01	0.077	0.19	8	-0.24	24	32
ARF6/GDP/GULP/ACAP1	0.029	0.084	-10000	0	-0.21	26	26
alphaIIb/beta3 Integrin/paxillin/GIT1	0.082	0.058	-10000	0	-0.11	34	34
ACAP1	0	0	0	4	0	1	5
ACAP2	0	0	0	6	0	34	40
LHCGR/beta Arrestin2	0.031	0.026	-10000	0	-0.063	32	32
EFNA1	0.034	0.017	-10000	0	0	107	107
HGF	0.04	0.009	-10000	0	0	29	29
CYTH3	0	0	0.001	10	-0.001	34	44
CYTH2	0	0.001	0.003	4	-0.004	37	41
NCK1	0.036	0.015	-10000	0	0	80	80
fibronectin binding	0	0	0	8	0	33	41
endosomal lumen acidification	0	0	0	10	0	20	30
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.032	0.018	-10000	0	0	129	129
GNAQ/ARNO	0.027	0.009	-10000	0	0	49	49
mol:Phosphatidic acid	0	0	0	6	0	34	40
PIP3-E	0.038	0.012	-10000	0	0	52	52
MET	0.027	0.02	-10000	0	0	198	198
GNA14	0.04	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GIT1	0.04	0.009	-10000	0	0	27	27
mol:PI-4-5-P2	0	0	0.001	13	-0.001	34	47
GNA11	0.037	0.013	-10000	0	0	61	61
LHCGR	0.04	0.009	-10000	0	0	25	25
AGTR1	0.037	0.014	-10000	0	0	68	68
desensitization of G-protein coupled receptor protein signaling pathway	0.031	0.026	-10000	0	-0.063	32	32
IPCEF1/ARNO	0.054	0.044	-10000	0	-0.087	35	35
alphaIIb/beta3 Integrin	0.04	0.05	-10000	0	-0.14	34	34

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.14	0.36	1	-0.59	15	16
CRKL	0.025	0.085	0.18	114	-0.16	2	116
mol:DAG	0.044	0.073	0.22	4	-0.22	16	20
HRAS	0.018	0.097	0.25	40	-0.18	3	43
MAPK8	0.011	0.078	0.18	83	-0.13	6	89
RAP1A	0.024	0.085	0.18	114	-0.16	3	117
GAB1	0.023	0.083	0.18	107	-0.16	2	109
MAPK14	0.012	0.081	0.18	87	-0.13	6	93
EPO	0.045	0.015	0.083	5	-0.038	7	12
PLCG1	0.045	0.074	0.22	4	-0.22	16	20
EPOR/TRPC2/IP3 Receptors	0.04	0.019	0.082	4	-0.038	6	10
RAPGEF1	0.04	0.008	-10000	0	0	23	23
EPO/EPOR (dimer)/SOCS3	0.064	0.051	-10000	0	-0.13	16	16
GAB1/SHC/GRB2/SOS1	0.069	0.081	0.26	16	-0.16	6	22
EPO/EPOR (dimer)	0.057	0.033	-10000	0	-0.09	5	5
IRS2	0.024	0.084	0.18	111	-0.16	2	113
STAT1	0.036	0.096	0.24	4	-0.26	23	27
STAT5B	0.046	0.077	0.24	4	-0.21	20	24
cell proliferation	0.005	0.078	0.17	87	-0.14	7	94
GAB1/SHIP/PIK3R1/SHP2/SHC	0.036	0.061	0.16	3	-0.17	5	8
TEC	0.018	0.081	0.18	96	-0.18	8	104
SOCS3	0.037	0.014	-10000	0	0	67	67
STAT1 (dimer)	0.036	0.095	0.24	5	-0.26	23	28
JAK2	0.039	0.02	0.082	6	-0.037	4	10
PIK3R1	0.034	0.017	-10000	0	0	108	108
EPO/EPOR (dimer)/JAK2	0.07	0.07	0.24	34	-0.1	25	59
EPO/EPOR	0.057	0.033	-10000	0	-0.09	5	5
LYN	0.036	0.018	-10000	0	-0.037	9	9
TEC/VAV2	0.032	0.076	0.22	28	-0.17	11	39
elevation of cytosolic calcium ion concentration	0.04	0.019	0.082	4	-0.038	6	10
SHC1	0.04	0.01	-10000	0	0	31	31
EPO/EPOR (dimer)/LYN	0.062	0.062	-10000	0	-0.11	33	33
mol:IP3	0.044	0.073	0.22	4	-0.22	16	20
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.045	0.072	0.21	39	-0.14	4	43
SH2B3	0	0.008	0.032	11	-10000	0	11
NFKB1	0.008	0.076	0.18	70	-0.16	7	77
EPO/EPOR (dimer)/JAK2/SOCS3	0.016	0.047	0.21	2	-0.16	28	30
PTPN6	0.033	0.062	0.17	67	-0.12	7	74
TEC/VAV2/GRB2	0.051	0.086	0.23	33	-0.17	11	44
EPOR	0.04	0.019	0.083	4	-0.038	6	10
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.068	0.081	0.23	29	-0.16	6	35
SOS1	0.038	0.013	-10000	0	0	56	56
PLCG2	0.035	0.015	-10000	0	0	87	87
CRKL/CBL/C3G	0.072	0.077	0.23	44	-0.19	2	46
VAV2	0.022	0.083	0.18	105	-0.16	3	108
CBL	0.026	0.087	0.18	120	-0.19	2	122
SHC/Grb2/SOS1	0.038	0.057	0.17	2	-0.13	13	15
STAT5A	0.046	0.08	0.24	4	-0.22	22	26
GRB2	0.041	0.007	-10000	0	0	17	17
STAT5 (dimer)	0.063	0.092	0.28	4	-0.28	13	17
LYN/PLCgamma2	0.038	0.051	-10000	0	-0.13	36	36
PTPN11	0.04	0.009	-10000	0	0	27	27
BTK	0.024	0.085	0.18	113	-0.17	6	119
BCL2	0.028	0.12	0.36	1	-0.48	10	11

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.008	0.054	0.17	51	-0.092	3	54
BUB1B	-0.024	0.082	0.12	1	-0.21	67	68
PLK1	-0.001	0.037	0.076	5	-0.099	42	47
PLK1S1	-0.001	0.021	0.044	8	-0.055	40	48
KIF2A	-0.001	0.033	0.067	5	-0.09	41	46
regulation of mitotic centrosome separation	-0.001	0.037	0.076	5	-0.1	41	46
GOLGA2	0.04	0.009	-10000	0	0	26	26
Hec1/SPC24	-0.01	0.025	-10000	0	-0.08	47	47
WEE1	-0.012	0.088	-10000	0	-0.33	29	29
cytokinesis	-0.038	0.13	0.14	4	-0.27	111	115
PP2A-alpha B56	-0.008	0.25	-10000	0	-0.68	65	65
AURKA	-0.001	0.023	0.05	9	-0.063	34	43
PICH/PLK1	-0.032	0.069	0.073	1	-0.16	106	107
CENPE	-0.007	0.035	0.15	2	-0.13	20	22
RhoA/GTP	0.03	0.012	-10000	0	-0.13	3	3
positive regulation of microtubule depolymerization	-0.001	0.033	0.067	5	-0.09	41	46
PPP2CA	0.04	0.009	-10000	0	0	26	26
FZR1	0.038	0.013	-10000	0	0	56	56
TPX2	-0.025	0.099	-10000	0	-0.25	89	89
PAK1	0.037	0.014	-10000	0	0	70	70
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.009	-10000	0	0	25	25
CLSPN	0.009	0.037	-10000	0	-0.26	7	7
GORASP1	0.041	0.006	-10000	0	0	10	10
metaphase	0	0.004	0.016	13	-0.013	26	39
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.001	0.021	0.044	8	-0.055	40	48
G2 phase of mitotic cell cycle	-0.001	0.003	0.011	19	-10000	0	19
STAG2	0.039	0.01	-10000	0	0	35	35
GRASP65/GM130/RAB1/GTP	0.016	0.069	-10000	0	-0.62	5	5
spindle elongation	-0.001	0.037	0.076	5	-0.1	41	46
ODF2	0.04	0.009	-10000	0	0	27	27
BUB1	-0.046	0.25	-10000	0	-0.72	65	65
TPT1	-0.002	0.051	-10000	0	-0.19	33	33
CDC25C	-0.007	0.089	-10000	0	-0.33	37	37
CDC25B	0.024	0.03	-10000	0	-0.03	106	106
SGOL1	-0.008	0.054	0.093	3	-0.17	51	54
RHOA	0.041	0.007	-10000	0	0	14	14
CCNB1/CDK1	0.004	0.13	-10000	0	-0.21	122	122
CDC14B	-0.01	0.005	0.011	30	-10000	0	30
CDC20	0.034	0.016	-10000	0	0	104	104
PLK1/PBIP1	-0.003	0.032	-10000	0	-0.1	33	33
mitosis	-0.001	0.003	0.012	13	-0.011	7	20
FBXO5	-0.015	0.063	0.1	4	-0.16	64	68
CDC2	0.028	0.022	-10000	0	-0.029	16	16
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.054	-10000	0	-0.25	20	20
ERCC6L	-0.03	0.098	-10000	0	-0.2	119	119
NLP/gamma Tubulin	-0.001	0.032	0.066	3	-0.087	47	50
microtubule cytoskeleton organization	-0.002	0.051	-10000	0	-0.19	33	33
G2/M transition DNA damage checkpoint	0	0.003	0.011	13	-10000	0	13
PPP1R12A	0.04	0.01	-10000	0	0	31	31
interphase	0	0.003	0.011	13	-10000	0	13
PLK1/PRC1-2	0.014	0.083	-10000	0	-0.16	84	84
GRASP65/GM130/RAB1/GTP/PLK1	0.051	0.06	-10000	0	-0.12	33	33
RAB1A	0.04	0.009	-10000	0	0	29	29
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.001	0.026	0.058	13	-0.067	39	52
mitotic prometaphase	-0.001	0.004	0.019	19	-10000	0	19
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.066	-10000	0	-0.23	25	25
microtubule-based process	0.014	0.052	-10000	0	-0.14	36	36
Golgi organization	-0.001	0.037	0.076	5	-0.1	41	46
Cohesin/SA2	0.014	0.047	0.11	1	-0.098	59	60
PPP1CB/MYPT1	0.05	0.042	-10000	0	-0.14	23	23
KIF20A	0.032	0.018	-10000	0	0	133	133
APC/C/CDC20	0.017	0.051	0.098	1	-0.13	39	40
PPP2R1A	0.039	0.011	-10000	0	0	42	42
chromosome segregation	-0.003	0.032	-10000	0	-0.1	33	33
PRC1	0.036	0.015	-10000	0	0	82	82
ECT2	0.037	0.12	0.21	140	-0.16	44	184
C13orf34	0	0.029	0.065	8	-0.077	39	47
NUDC	0.002	0.054	-10000	0	-0.25	20	20
regulation of attachment of spindle microtubules to kinetochore	-0.024	0.081	0.12	1	-0.21	67	68
spindle assembly	-0.001	0.034	0.07	11	-0.092	39	50
spindle stabilization	-0.001	0.021	0.043	8	-0.055	40	48
APC/C/HCDH1	0.032	0.012	-10000	0	-10000	0	0
MKLP2/PLK1	0.014	0.052	-10000	0	-0.14	36	36
CCNB1	0.026	0.027	-10000	0	-0.03	63	63
PPP1CB	0.04	0.01	-10000	0	0	33	33
BTRC	0.04	0.008	-10000	0	0	21	21
ROCK2	-0.006	0.095	-10000	0	-0.32	41	41
TUBG1	-0.002	0.054	-10000	0	-0.2	33	33
G2/M transition of mitotic cell cycle	-0.035	0.1	0.13	16	-0.21	114	130
MLF1IP	-0.008	0.007	0.011	50	-10000	0	50
INCENP	0.041	0.005	-10000	0	0	5	5

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.003	0.07	-10000	0	-0.19	53	53
epithelial cell differentiation	0.056	0.069	-10000	0	-0.13	51	51
CYFIP2	0.038	0.012	-10000	0	0	47	47
ENAH	-0.033	0.071	0.22	13	-0.22	4	17
EGFR	0.037	0.014	-10000	0	0	72	72
EPHA2	0.039	0.01	-10000	0	0	35	35
MYO6	-0.03	0.048	0.18	7	-0.21	17	24
CTNNB1	0.04	0.01	-10000	0	0	31	31
ABI1/Sra1/Nap1	0.061	0.059	-10000	0	-0.12	41	41
AQP5	-0.076	0.14	0.18	4	-0.37	97	101
CTNND1	0.041	0.007	-10000	0	0	17	17
mol:PI-4-5-P2	-0.03	0.043	0.18	6	-0.2	12	18
regulation of calcium-dependent cell-cell adhesion	-0.028	0.043	0.18	6	-0.2	12	18
EGF	0.038	0.012	-10000	0	0	53	53
NCKAP1	0.04	0.01	-10000	0	0	31	31
AQP3	-0.024	0.058	0.18	4	-0.29	15	19
cortical microtubule organization	0.056	0.069	-10000	0	-0.13	51	51
GO:0000145	-0.03	0.039	0.16	6	-0.19	12	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.062	0.072	-10000	0	-0.13	51	51
MLLT4	0.034	0.017	-10000	0	0	107	107
ARF6/GDP	-0.05	0.046	-10000	0	-0.2	23	23
ARF6	0.041	0.008	-10000	0	0	19	19
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.077	-10000	0	-0.12	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.017	0.048	0.2	4	-0.21	15	19
PVRL2	0.039	0.011	-10000	0	0	44	44
ZYX	-0.028	0.039	0.18	5	-0.2	8	13
ARF6/GTP	0.066	0.083	-10000	0	-0.12	62	62
CDH1	0.035	0.016	-10000	0	0	98	98
EGFR/EGFR/EGF/EGF	0.037	0.075	-10000	0	-0.13	66	66
RhoA/GDP	0.056	0.072	-10000	0	-0.13	50	50
actin cytoskeleton organization	-0.032	0.048	0.16	6	-0.23	16	22
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	118	118
GIT1	0.04	0.009	-10000	0	0	27	27
IGF1R	0.033	0.017	-10000	0	0	118	118
IGF1	0.036	0.015	-10000	0	0	84	84
DIAPH1	-0.002	0.22	-10000	0	-0.57	63	63
Wnt receptor signaling pathway	-0.056	0.069	0.13	51	-10000	0	51
RHOA	0.041	0.007	-10000	0	0	14	14
RhoA/GTP	-0.049	0.045	-10000	0	-0.19	22	22
CTNNA1	0.039	0.011	-10000	0	0	38	38
VCL	-0.033	0.049	0.16	6	-0.24	16	22
EFNA1	0.034	0.017	-10000	0	0	107	107
LPP	-0.029	0.044	0.17	6	-0.2	14	20
Ephrin A1/EPHA2	0.032	0.077	-10000	0	-0.13	74	74
SEC6/SEC8	-0.045	0.043	-10000	0	-0.19	21	21
MGAT3	-0.029	0.044	0.18	6	-0.2	12	18
HGF/MET	0.016	0.087	-10000	0	-0.13	113	113
HGF	0.04	0.009	-10000	0	0	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.003	0.07	-10000	0	-0.19	53	53
actin cable formation	0.002	0.097	0.25	28	-0.25	14	42
KIAA1543	-0.033	0.043	0.17	6	-0.2	13	19
KIFC3	-0.032	0.041	0.18	5	-0.2	12	17
NCK1	0.036	0.015	-10000	0	0	80	80
EXOC3	0.041	0.005	-10000	0	0	8	8
ACTN1	-0.031	0.049	0.18	7	-0.22	16	23
NCK1/GIT1	0.044	0.047	-10000	0	-0.14	30	30
mol:GDP	0.056	0.069	-10000	0	-0.13	51	51
EXOC4	0.038	0.012	-10000	0	0	49	49
STX4	-0.029	0.034	-10000	0	-0.12	49	49
PIP5K1C	-0.031	0.043	0.18	6	-0.2	12	18
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.04	0.009	-10000	0	0	26	26
ROCK1	-0.026	0.085	0.26	12	-0.23	4	16
adherens junction assembly	-0.05	0.13	-10000	0	-0.4	42	42
IGF-1R heterotetramer/IGF1	0.023	0.083	-10000	0	-0.13	94	94
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.051	-10000	0	-0.14	34	34
MET	0.027	0.02	-10000	0	0	198	198
PLEKHA7	-0.031	0.045	0.18	7	-0.2	14	21
mol:GTP	0.058	0.075	-10000	0	-0.12	61	61
establishment of epithelial cell apical/basal polarity	-0.038	0.056	0.14	25	-0.2	16	41
cortical actin cytoskeleton stabilization	0.003	0.07	-10000	0	-0.19	53	53
regulation of cell-cell adhesion	-0.032	0.048	0.16	6	-0.23	16	22
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.003	0.07	-10000	0	-0.19	53	53

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.038	0.012	-10000	0	0	54	54
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.04	0.008	-10000	0	0	23	23
TCEB1	0.038	0.012	-10000	0	0	50	50
HIF1A/p53	0	0.086	0.22	1	-0.25	41	42
HIF1A	-0.001	0.072	0.16	3	-0.25	29	32
COPS5	0.036	0.015	-10000	0	0	86	86
VHL/Elongin B/Elongin C/RBX1/CUL2	0.086	0.071	-10000	0	-0.12	26	26
FIH (dimer)	0.04	0.009	-10000	0	0	25	25
CDKN2A	0.029	0.019	-10000	0	0	175	175
ARNT/IPAS	0.054	0.025	-10000	0	-0.14	4	4
HIF1AN	0.04	0.009	-10000	0	0	25	25
GNB2L1	0.041	0.005	-10000	0	0	7	7
HIF1A/ARNT	0.015	0.085	0.22	1	-0.24	35	36
CUL2	0.039	0.01	-10000	0	0	36	36
OS9	0.039	0.011	-10000	0	0	38	38
RACK1/Elongin B/Elongin C	0.071	0.038	-10000	0	-0.12	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.005	0.073	0.15	3	-0.26	27	30
PHD1-3/OS9	0.053	0.08	-10000	0	-0.11	86	86
HIF1A/RACK1/Elongin B/Elongin C	0.048	0.09	-10000	0	-0.26	27	27
VHL	0.04	0.009	-10000	0	0	28	28
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	0.012	0.08	0.22	1	-0.25	31	32
EGLN3	0.028	0.02	-10000	0	0	187	187
EGLN2	0.04	0.009	-10000	0	0	29	29
EGLN1	0.039	0.01	-10000	0	0	36	36
TP53	0.026	0.02	-10000	0	0	213	213
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.024	0.12	-10000	0	-0.53	24	24
ARNT	0.041	0.006	-10000	0	0	12	12
ARD1A	0.04	0.01	-10000	0	0	31	31
RBX1	0.037	0.014	-10000	0	0	71	71
HIF1A/p19ARF	0.004	0.085	-10000	0	-0.27	33	33

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.03	0.18	-10000	0	-0.51	26	26
RAD9A	0.042	0.004	-10000	0	0	6	6
AP1	0.002	0.084	-10000	0	-0.15	115	115
IFNAR2	0.03	0.027	-10000	0	-0.033	70	70
AKT1	0.013	0.038	-10000	0	-0.15	6	6
ER alpha/Oestrogen	0.013	0.044	-10000	0	-0.13	44	44
NFX1/SIN3/HDAC complex	0.001	0.084	0.17	5	-0.26	32	37
EGF	0.038	0.013	-10000	0	0	53	53
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.045	0.043	-10000	0	-0.13	6	6
TERT/c-Abl	-0.019	0.18	-10000	0	-0.48	28	28
SAP18	0.039	0.01	-10000	0	0	34	34
MRN complex	0.048	0.071	-10000	0	-0.15	50	50
WT1	0.029	0.027	-10000	0	-0.033	68	68
WRN	0.033	0.017	-10000	0	0	124	124
SP1	0.032	0.031	-10000	0	-0.041	79	79
SP3	0.041	0.008	-10000	0	-0.002	14	14
TERF2IP	0.036	0.014	-10000	0	0	75	75
Telomerase/Nucleolin	-0.018	0.18	-10000	0	-0.44	37	37
Mad/Max	0.055	0.024	-10000	0	-10000	0	0
TERT	-0.032	0.18	-10000	0	-0.52	25	25
CCND1	-0.11	0.37	-10000	0	-0.97	81	81
MAX	0.04	0.009	-10000	0	-0.003	18	18
RBBP7	0.04	0.009	-10000	0	0	26	26
RBBP4	0.038	0.012	-10000	0	0	46	46
TERF2	0.035	0.021	0.095	44	0	79	123
PTGES3	0.038	0.013	-10000	0	0	56	56
SIN3A	0.04	0.009	-10000	0	0	28	28
Telomerase/911	0.024	0.081	-10000	0	-0.29	21	21
CDKN1B	-0.002	0.083	0.2	4	-0.33	22	26
RAD1	0.038	0.013	-10000	0	0	57	57
XRCC5	0.039	0.011	-10000	0	0	39	39
XRCC6	0.037	0.014	-10000	0	0	70	70
SAP30	0.038	0.013	-10000	0	0	55	55
TRF2/PARP2	0.049	0.035	-10000	0	-0.13	9	9
UBE3A	0.041	0.006	-10000	0	0	7	7
JUN	0.036	0.015	-10000	0	0	81	81
E6	0	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.023	0.027	-10000	0	-0.051	30	30
FOS	0.026	0.021	-10000	0	0	210	210
IFN-gamma/IRF1	0.025	0.082	-10000	0	-0.16	81	81
PARP2	0.04	0.009	-10000	0	0	30	30
BLM	0.037	0.014	-10000	0	0	67	67
Telomerase	0.004	0.061	-10000	0	-0.26	18	18
IRF1	0.029	0.041	0.11	1	-0.14	21	22
ESR1	0.035	0.016	-10000	0	0	92	92
KU/TER	0.043	0.054	-10000	0	-0.16	31	31
ATM/TRF2	0.037	0.056	-10000	0	-0.14	41	41
ubiquitin-dependent protein catabolic process	0.004	0.084	0.18	5	-0.27	26	31
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.004	0.085	0.18	5	-0.28	25	30
HDAC1	0.038	0.013	-10000	0	0	56	56
HDAC2	0.03	0.03	-10000	0	-0.04	74	74
ATM	0.009	0.066	-10000	0	-0.24	32	32
SMAD3	-0.013	0.016	0.025	70	-10000	0	70
ABL1	0.039	0.011	-10000	0	0	41	41
MXD1	0.04	0.009	-10000	0	-0.002	19	19
MRE11A	0.038	0.012	-10000	0	0	54	54
HUS1	0.04	0.008	-10000	0	0	20	20
RPS6KB1	0.039	0.011	-10000	0	0	38	38
TERT/NF kappa B1/14-3-3	-0.008	0.19	-10000	0	-0.51	22	22
NR2F2	0.04	0.013	-10000	0	0	38	38
MAPK3	-0.016	0.015	0.022	51	-0.041	1	52
MAPK1	-0.015	0.015	0.022	47	-0.041	1	48
TGFB1/TGF beta receptor Type II	0.037	0.013	-10000	0	0	62	62
NFKB1	0.036	0.015	-10000	0	0	84	84
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.009	0.065	-10000	0	-0.24	32	32
NBN	0.035	0.016	-10000	0	0	96	96
EGFR	0.036	0.014	-10000	0	0	72	72
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.04	0.052	-10000	0	-0.14	37	37
MYC	0.022	0.021	-10000	0	0	268	268
IL2	0.03	0.031	-10000	0	-0.042	74	74
KU	0.043	0.054	-10000	0	-0.16	31	31
RAD50	0.039	0.011	-10000	0	0	42	42
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.037	0.013	-10000	0	0	62	62
TRF2/BLM	0.043	0.044	-10000	0	-0.13	21	21
FRAP1	0.04	0.009	-10000	0	0	27	27
KU/TERT	-0.012	0.19	-10000	0	-0.48	29	29
SP1/HDAC2	0.043	0.05	-10000	0	-0.11	16	16
PINX1	0.033	0.017	-10000	0	0	123	123
Telomerase/EST1A	-0.025	0.17	-10000	0	-0.44	34	34
Smad3/Myc	0.015	0.038	-10000	0	-0.15	19	19
911 complex	0.071	0.037	-10000	0	-0.12	9	9
IFNG	0.034	0.036	0.11	2	-0.11	26	28
Telomerase/PinX1	-0.025	0.17	-10000	0	-0.44	34	34
Telomerase/AKT1/mTOR/p70S6K	-0.001	0.1	-10000	0	-0.31	32	32
SIN3B	0.037	0.013	-10000	0	0	65	65
YWHAE	0.038	0.013	-10000	0	0	58	58
Telomerase/EST1B	-0.025	0.17	-10000	0	-0.44	34	34
response to DNA damage stimulus	0.001	0.035	0.063	3	-0.11	49	52
MRN complex/TRF2/Rap1	0.065	0.081	-10000	0	-0.14	38	38
TRF2/WRN	0.038	0.041	-10000	0	-0.11	21	21
Telomerase/hnRNP C1/C2	-0.025	0.17	-10000	0	-0.44	34	34
E2F1	0.031	0.027	-10000	0	-0.033	69	69
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.04	0.009	-10000	0	0	30	30
DKC1	0.04	0.008	-10000	0	0	20	20
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.017	0.007	-10000	0	-10000	0	0
SMARCC1	-0.014	0.18	-10000	0	-1.1	14	14
REL	0.04	0.008	-10000	0	0	20	20
HDAC7	-0.045	0.093	0.21	7	-0.22	66	73
JUN	0.036	0.015	-10000	0	0	80	80
EP300	0.037	0.014	-10000	0	0	73	73
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.012	0.022	0.063	15	-10000	0	15
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	-0.002	0.12	0.28	6	-0.22	80	86
MAP2K6	0.029	0.025	-10000	0	-0.034	48	48
BRM/BAF57	0.032	0.059	-10000	0	-0.13	53	53
MAP2K4	0.032	0.024	-10000	0	-0.034	45	45
SMARCA2	0.032	0.018	-10000	0	0	135	135
PDE9A	-0.081	0.32	-10000	0	-0.83	82	82
NCOA2	0.037	0.014	-10000	0	0	71	71
CEBPA	0.037	0.014	-10000	0	0	67	67
EHMT2	0.041	0.007	-10000	0	0	18	18
cell proliferation	-0.014	0.12	0.29	12	-0.3	34	46
NR0B1	0.039	0.011	-10000	0	0	38	38
EGR1	0.028	0.02	-10000	0	0	194	194
RXRs/9cRA	0.064	0.035	-10000	0	-0.1	3	3
AR/RACK1/Src	-0.013	0.094	0.21	31	-0.22	20	51
AR/GR	-0.012	0.093	0.23	1	-0.19	85	86
GNB2L1	0.042	0.005	-10000	0	0	7	7
PKN1	0.035	0.016	-10000	0	0	99	99
RCHY1	0.037	0.014	-10000	0	0	72	72
epidermal growth factor receptor activity	0	0	0.003	1	-10000	0	1
MAPK8	-0.013	0.021	0.051	7	-0.059	1	8
T-DHT/AR/TIF2/CARM1	0.004	0.088	0.25	5	-0.21	23	28
SRC	-0.015	0.068	0.17	45	-0.16	7	52
NR3C1	0.039	0.012	-10000	0	0	46	46
KLK3	0.005	0.072	-10000	0	-10000	0	0
APPBP2	0.031	0.026	-10000	0	-0.034	65	65
TRIM24	0.039	0.012	-10000	0	0	44	44
T-DHT/AR/TIP60	-0.035	0.059	0.088	4	-0.16	59	63
TMPRSS2	0.016	0.11	-10000	0	-0.58	11	11
RXRG	0.036	0.015	-10000	0	0	86	86
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.04	0.01	-10000	0	0	33	33
RXRB	0.041	0.007	-10000	0	0	17	17
CARM1	0.037	0.014	-10000	0	0	69	69
NR2C2	0.041	0.007	-10000	0	0	16	16
KLK2	0	0.077	0.26	1	-0.29	5	6
AR	-0.019	0.079	0.15	12	-0.19	73	85
SENP1	0.039	0.01	-10000	0	0	35	35
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.038	0.01	-10000	0	0	35	35
SRY	0.041	0.002	-10000	0	0	2	2
GATA2	0.039	0.01	-10000	0	0	35	35
MYST2	0.04	0.009	-10000	0	0	27	27
HOXB13	0.04	0.011	-10000	0	0	38	38
T-DHT/AR/RACK1/Src	-0.016	0.097	0.22	33	-0.23	22	55
positive regulation of transcription	0.039	0.01	-10000	0	0	35	35
DNAJA1	0.031	0.026	-10000	0	-0.034	64	64
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.089	0.17	21	-0.26	49	70
NCOA1	0.041	0.035	0.12	3	-0.18	12	15
SPDEF	0.038	0.015	-10000	0	0	72	72
T-DHT/AR/TIF2	-0.012	0.095	0.2	9	-0.25	43	52
T-DHT/AR/Hsp90	-0.035	0.059	0.088	4	-0.16	59	63
GSK3B	0.04	0.009	-10000	0	0	26	26
NR2C1	0.039	0.011	-10000	0	0	41	41
mol:T-DHT	-0.023	0.052	0.19	13	-0.16	7	20
SIRT1	0.041	0.008	-10000	0	0	20	20
ZMIZ2	-0.001	0.001	-10000	0	-0.012	2	2
POU2F1	0.034	0.056	0.12	4	-0.1	73	77
T-DHT/AR/DAX-1	-0.02	0.082	0.2	16	-0.22	22	38
CREBBP	0.038	0.012	-10000	0	0	54	54
SMARCE1	0.039	0.011	-10000	0	0	43	43

×

Canonical NF-kappaB 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
FBXW11	0.036	0.028	0.091	2	-0.07	31	33
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.13	0.24	4	-0.28	61	65
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.015	0.041	-10000	0	-0.13	41	41
NFKBIA	-0.036	0.067	0.25	3	-0.27	32	35
BIRC2	0.036	0.014	-10000	0	0	75	75
IKBKB	0.039	0.011	-10000	0	0	44	44
RIPK2	0.033	0.017	-10000	0	0	125	125
IKBKG	-0.005	0.11	-10000	0	-0.3	48	48
IKK complex/A20	0.033	0.12	-10000	0	-0.32	29	29
NEMO/A20/RIP2	0.033	0.017	-10000	0	0	125	125
XPO1	0.039	0.011	-10000	0	0	39	39
NEMO/ATM	0.003	0.13	-10000	0	-0.35	39	39
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	13	13
Exportin 1/RanGTP	0.047	0.035	-10000	0	-0.11	24	24
IKK complex/ELKS	0.006	0.11	-10000	0	-0.32	36	36
BCL10/MALT1/TRAF6	0.065	0.047	-10000	0	-0.12	20	20
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.032	0.028	0.084	1	-0.072	26	27
RELA	0.036	0.028	0.097	1	-0.069	34	35
MALT1	0.036	0.014	-10000	0	0	76	76
cIAP1/UbcH5C	0.04	0.053	-10000	0	-0.14	38	38
ATM	0.036	0.014	-10000	0	0	73	73
TNF/TNFR1A	0.047	0.038	-10000	0	-0.14	15	15
TRAF6	0.04	0.008	-10000	0	0	22	22
PRKCA	0.035	0.015	-10000	0	0	90	90
CHUK	0.038	0.012	-10000	0	0	52	52
UBE2D3	0.038	0.012	-10000	0	0	48	48
TNF	0.04	0.009	-10000	0	0	26	26
NF kappa B1 p50/RelA	0.057	0.082	-10000	0	-0.15	62	62
BCL10	0.041	0.006	-10000	0	0	11	11
proteasomal ubiquitin-dependent protein catabolic process	-0.036	0.066	0.25	3	-0.27	32	35
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.028	0.087	3	-0.07	31	34
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
IKK complex	0.019	0.13	-10000	0	-0.34	35	35
CYLD	0.038	0.012	-10000	0	0	51	51
IKK complex/PKC alpha	0.023	0.13	-10000	0	-0.33	37	37

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.046	0.051	-10000	0	-0.14	35	35
Necdin/E2F1	0.045	0.041	-10000	0	-0.14	17	17
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.072	0.061	-10000	0	-0.11	42	42
NGF (dimer)/p75(NTR)/BEX1	0.022	0.053	-10000	0	-0.11	63	63
NT-4/5 (dimer)/p75(NTR)	0.029	0.009	-10000	0	-0.13	1	1
IKBKB	0.039	0.011	-10000	0	0	44	44
AKT1	0.016	0.09	0.19	101	-0.18	6	107
IKBKG	0.042	0.003	-10000	0	0	2	2
BDNF	0.04	0.008	-10000	0	0	23	23
MGDIs/NGR/p75(NTR)/LINGO1	0.049	0.022	-10000	0	-0.11	3	3
FURIN	0.04	0.01	-10000	0	0	32	32
proBDNF (dimer)/p75(NTR)/Sortilin	0.066	0.049	-10000	0	-0.12	26	26
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.02	0.071	-10000	0	-0.13	79	79
proBDNF (dimer)	0.04	0.008	-10000	0	0	23	23
NTRK1	0.039	0.01	-10000	0	0	35	35
RTN4R	0.038	0.012	-10000	0	0	54	54
neuron apoptosis	-0.059	0.13	0.36	1	-0.38	46	47
IRAK1	0.041	0.007	-10000	0	0	18	18
SHC1	0.017	0.01	0.069	8	-0.11	1	9
ARHGDIA	0.038	0.012	-10000	0	0	55	55
RhoA/GTP	0.03	0.012	-10000	0	-0.13	3	3
Gamma Secretase	0.073	0.087	-10000	0	-0.12	66	66
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.055	0.058	-10000	0	-0.11	51	51
MAGEH1	0.039	0.011	-10000	0	0	45	45
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.054	0.054	-10000	0	-0.1	41	41
Mammalian IAPs/DIABLO	0.012	0.089	-10000	0	-0.13	132	132
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.04	0.009	-10000	0	0	26	26
APP	0.038	0.012	-10000	0	0	51	51
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.042	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.047	0.027	0.19	1	-0.11	7	8
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.017	0.041	0.2	3	-10000	0	3
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.01	0.062	-10000	0	-0.16	52	52
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.05	0.023	-10000	0	-0.11	7	7
NCSTN	0.04	0.009	-10000	0	0	24	24
mol:GTP	0.045	0.035	-10000	0	-0.11	23	23
PSENEN	0.035	0.016	-10000	0	0	92	92
mol:ceramide	-0.021	0.028	0.19	3	-10000	0	3
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.011	0.091	-10000	0	-0.33	20	20
p75(NTR)/beta APP	0.047	0.045	-10000	0	-0.14	28	28
BEX1	0.027	0.02	-10000	0	0	205	205
mol:GDP	-0.008	0.004	-10000	0	-0.1	1	1
NGF (dimer)	-0.004	0.075	-10000	0	-0.1	173	173
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.064	0.037	-10000	0	-0.11	8	8
PIK3R1	0.034	0.017	-10000	0	0	108	108
RAC1/GTP	0.044	0.016	-10000	0	-0.06	2	2
MYD88	0.041	0.007	-10000	0	0	14	14
CHUK	0.038	0.012	-10000	0	0	52	52
NGF (dimer)/p75(NTR)/PKA	0.045	0.035	-10000	0	-0.11	23	23
RHOB	0.04	0.008	-10000	0	0	21	21
RHOA	0.041	0.007	-10000	0	0	14	14
MAGE-G1/E2F1	0.053	0.025	-10000	0	-0.14	2	2
NT3 (dimer)	0.031	0.018	-10000	0	0	147	147
TP53	-0.023	0.048	0.21	9	-0.18	13	22
PRDM4	-0.022	0.028	0.19	3	-10000	0	3
BDNF (dimer)	0.019	0.091	-10000	0	-0.11	166	166
PIK3CA	0.03	0.019	-10000	0	0	155	155
SORT1	0.039	0.012	-10000	0	0	46	46
activation of caspase activity	0.065	0.057	-10000	0	-0.11	42	42
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.062	0.049	-10000	0	-0.11	33	33
RHOC	0.041	0.006	-10000	0	0	12	12
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.016	0.057	0.24	5	-0.2	15	20
DIABLO	0.037	0.013	-10000	0	0	63	63
SMPD2	-0.021	0.028	0.19	3	-10000	0	3
APH1B	0.036	0.015	-10000	0	0	83	83
APH1A	0.041	0.006	-10000	0	0	10	10
proNGF (dimer)/p75(NTR)/Sortilin	0.044	0.038	-10000	0	-0.11	27	27
PSEN1	0.039	0.01	-10000	0	0	35	35
APAF-1/Pro-Caspase 9	0.051	0.041	-10000	0	-0.15	19	19
NT3 (dimer)/p75(NTR)	0.041	0.037	-10000	0	-0.14	10	10
MAPK8	-0.02	0.064	0.25	6	-0.23	13	19
MAPK9	-0.02	0.061	0.24	5	-0.23	10	15
APAF1	0.04	0.01	-10000	0	0	32	32
NTF3	0.031	0.018	-10000	0	0	147	147
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.036	0.014	-10000	0	0	77	77
RAC1/GDP	0.029	0.01	-10000	0	-0.13	1	1
RhoA-B-C/GDP	0.074	0.05	-10000	0	-0.1	27	27
p75 CTF/Sortilin/TRAF6/NRIF	0.075	0.076	-10000	0	-0.13	57	57
RhoA-B-C/GTP	0.044	0.034	-10000	0	-0.1	23	23
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.099	0.065	-10000	0	-0.11	32	32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.084	0.059	-10000	0	-0.12	32	32
PRKACB	0.038	0.012	-10000	0	0	48	48
proBDNF (dimer)/p75 ECD	0.046	0.047	-10000	0	-0.14	31	31
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.026	0.02	-10000	0	0	218	218
BIRC2	0.036	0.014	-10000	0	0	75	75
neuron projection morphogenesis	-0.019	0.05	0.15	4	-0.16	25	29
BAD	-0.024	0.068	0.26	4	-0.21	26	30
RIPK2	0.033	0.017	-10000	0	0	125	125
NGFR	0.04	0.009	-10000	0	0	28	28
CYCS	-0.026	0.033	0.19	2	-0.18	5	7
ADAM17	0.038	0.013	-10000	0	0	57	57
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.05	0.056	-10000	0	-0.1	45	45
BCL2L11	-0.025	0.068	0.26	4	-0.21	26	30
BDNF (dimer)/p75(NTR)	0.057	0.019	-10000	0	-0.14	1	1
PI3K	0.035	0.06	-10000	0	-0.12	48	48
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.061	0.047	-10000	0	-0.1	28	28
NDNL2	0.039	0.011	-10000	0	0	39	39
YWHAE	0.038	0.013	-10000	0	0	58	58
PRKCI	0.027	0.02	-10000	0	0	197	197
NGF (dimer)/p75(NTR)	0.029	0.009	-10000	0	-0.13	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.06	0.053	-10000	0	-0.11	40	40
TRAF6	0.04	0.008	-10000	0	0	22	22
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCZ	0.042	0	-10000	0	-10000	0	0
PLG	0.038	0.012	-10000	0	0	49	49
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.013	0.045	0.16	6	-0.16	26	32
SQSTM1	0.038	0.012	-10000	0	0	49	49
NGFRAP1	0.041	0.007	-10000	0	0	16	16
CASP3	-0.027	0.072	0.26	4	-0.23	28	32
E2F1	0.038	0.012	-10000	0	0	49	49
CASP9	0.04	0.009	-10000	0	0	26	26
IKK complex	0.046	0.099	-10000	0	-0.26	20	20
NGF (dimer)/TRKA	0.029	0.007	-10000	0	-10000	0	0
MMP7	0.016	0.02	-10000	0	0	340	340
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.079	0.054	-10000	0	-0.11	33	33
MMP3	0.038	0.013	-10000	0	0	59	59
APAF-1/Caspase 9	-0.056	0.061	-10000	0	-0.2	51	51

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.038	0.19	0.35	2	-0.98	21	23
VDR	0.038	0.013	-10000	0	0	56	56
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.023	0.091	-10000	0	-0.23	52	52
RXRs/LXRs/DNA/Oxysterols	0.016	0.13	-10000	0	-0.34	55	55
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0.001	0.016	0.057	1	-0.047	50	51
RARs/THRs/DNA/Src-1	-0.004	0.095	-10000	0	-0.18	113	113
RXRs/NUR77	0.079	0.072	0.3	1	-0.11	38	39
RXRs/PPAR	0.026	0.056	-10000	0	-0.16	13	13
NCOR2	0.04	0.009	-10000	0	0	28	28
VDR/VDR/Vit D3	0.023	0.031	-10000	0	-0.13	22	22
RARs/VDR/DNA/Vit D3	0.064	0.069	-10000	0	-0.11	59	59
RARA	0.039	0.01	-10000	0	0	35	35
NCOA1	0.04	0.009	-10000	0	0	28	28
VDR/VDR/DNA	0.038	0.013	-10000	0	0	56	56
RARs/RARs/DNA/9cRA	0.052	0.053	-10000	0	-0.1	46	46
RARG	0.04	0.009	-10000	0	0	27	27
RPS6KB1	-0.018	0.1	0.56	5	-0.42	22	27
RARs/THRs/DNA/SMRT	-0.003	0.09	-10000	0	-0.23	39	39
THRA	0.039	0.011	-10000	0	0	40	40
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.023	0.031	-10000	0	-0.13	22	22
RXRs/PPAR/9cRA/PGJ2/DNA	0.071	0.077	0.31	12	-0.15	33	45
NR1H4	0.041	0.007	-10000	0	0	16	16
RXRs/LXRs/DNA	0.095	0.1	0.32	1	-0.19	35	36
NR1H2	0.034	0.032	-10000	0	-0.059	52	52
NR1H3	0.035	0.034	-10000	0	-0.065	54	54
RXRs/VDR/DNA/Vit D3	0.072	0.071	0.28	1	-0.11	43	44
NR4A1	0.034	0.016	-10000	0	0	103	103
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.023	0.042	0.14	3	-0.14	9	12
RXRG	0.032	0.031	0.1	1	-0.055	44	45
RXR alpha/CCPG	0.026	0.022	-10000	0	-0.039	42	42
RXRA	0.035	0.031	0.1	1	-0.057	50	51
RXRB	0.036	0.034	0.1	1	-0.062	56	57
THRB	0.034	0.017	-10000	0	0	108	108
PPARG	0.039	0.01	-10000	0	0	37	37
PPARD	0.04	0.008	-10000	0	0	21	21
TNF	0.008	0.13	-10000	0	-0.5	10	10
mol:Oxysterols	0	0.015	0.027	1	-0.041	59	60
cholesterol transport	0.016	0.13	-10000	0	-0.34	55	55
PPARA	0.034	0.016	-10000	0	0	104	104
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.036	0.015	-10000	0	0	80	80
RXRs/NUR77/BCL2	0.021	0.047	-10000	0	-0.14	22	22
SREBF1	0.007	0.12	-10000	0	-0.51	9	9
RXRs/RXRs/DNA/9cRA	0.071	0.077	0.31	12	-0.15	33	45
ABCA1	-0.035	0.26	-10000	0	-0.79	56	56
RARs/THRs	0.07	0.092	-10000	0	-0.12	82	82
RXRs/FXR	0.088	0.068	0.3	1	-0.11	30	31
BCL2	0.036	0.014	-10000	0	0	76	76

×

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	0.049	0.023	-10000	0	-0.11	5	5
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.038	0.012	-10000	0	0	48	48
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.034	0.016	-10000	0	0	100	100
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.037	0.013	-10000	0	0	61	61
RAC1-CDC42/GTP/PAK family	0.007	0.049	-10000	0	-0.15	34	34
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.038	0.013	-10000	0	0	57	57
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.041	0.007	-10000	0	0	17	17
FYN	0.034	0.016	-10000	0	0	103	103
MAP3K12	0.041	0.007	-10000	0	0	14	14
FGR	0.041	0.007	-10000	0	0	17	17
p38 alpha/TAB1	0.002	0.12	0.2	1	-0.26	54	55
PRKG1	0.04	0.009	-10000	0	0	29	29
DUSP8	0.04	0.009	-10000	0	0	28	28
PGK/cGMP/p38 alpha	-0.003	0.11	0.18	1	-0.26	55	56
apoptosis	0.001	0.11	0.19	1	-0.25	55	56
RAL/GTP	0.046	0.037	-10000	0	-0.12	25	25
LYN	0.036	0.015	-10000	0	0	83	83
DUSP1	0.027	0.02	-10000	0	0	206	206
PAK1	0.037	0.014	-10000	0	0	70	70
SRC	0.039	0.01	-10000	0	0	36	36
RAC1/OSM/MEKK3/MKK3	0.091	0.04	-10000	0	-0.11	1	1
TRAF6	0.04	0.008	-10000	0	0	22	22
RAC1	0.039	0.01	-10000	0	0	34	34
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	0.041	0.007	-10000	0	0	17	17
RAC1-CDC42/GTP	0.05	0.023	-10000	0	-0.13	4	4
MAPK11	-0.028	0.12	0.2	2	-0.28	69	71
BLK	0.033	0.017	-10000	0	0	117	117
HCK	0.036	0.015	-10000	0	0	80	80
MAP2K3	0.038	0.012	-10000	0	0	47	47
DUSP16	0.036	0.015	-10000	0	0	86	86
DUSP10	0.034	0.017	-10000	0	0	109	109
TRAF6/MEKK3	0.049	0.021	-10000	0	-0.099	7	7
MAP3K7IP1	0.038	0.012	-10000	0	0	54	54
MAPK14	-0.011	0.12	0.19	3	-0.27	60	63
positive regulation of innate immune response	-0.024	0.14	0.23	2	-0.33	62	64
LCK	0.04	0.009	-10000	0	0	29	29
p38alpha-beta/MKP7	-0.013	0.14	0.24	2	-0.32	56	58
p38alpha-beta/MKP5	-0.018	0.14	0.24	2	-0.32	61	63
PGK/cGMP	0.029	0.007	-10000	0	-10000	0	0
PAK2	0.04	0.009	-10000	0	0	25	25
p38alpha-beta/MKP1	-0.029	0.14	0.25	1	-0.32	64	65
CDC42	0.04	0.009	-10000	0	0	24	24
RALB	0.04	0.009	-10000	0	0	26	26
RALA	0.04	0.009	-10000	0	0	30	30
PAK3	0.037	0.013	-10000	0	0	62	62

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.013	0.01	0.016	28	-10000	0	28
RAS family/GTP	0.017	0.1	0.26	2	-0.22	29	31
NFATC4	-0.017	0.082	0.25	20	-0.18	4	24
ERBB2IP	0.036	0.015	-10000	0	-0.002	74	74
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.001	0.079	0.18	8	-0.16	58	66
JUN	0.009	0.086	0.21	5	-10000	0	5
HRAS	0.04	0.01	-10000	0	0	31	31
DOCK7	-0.024	0.082	0.24	12	-0.21	10	22
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.037	0.08	0.21	27	-0.12	70	97
AKT1	-0.005	0.012	0.021	29	-10000	0	29
BAD	-0.015	0.007	0.012	13	-10000	0	13
MAPK10	-0.008	0.07	0.2	24	-0.14	4	28
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.001	0.085	0.2	2	-0.16	58	60
RAF1	0.008	0.11	0.26	26	-0.23	30	56
ErbB2/ErbB3/neuregulin 2	0.028	0.074	0.19	36	-0.12	76	112
STAT3	-0.027	0.25	-10000	0	-0.91	42	42
cell migration	-0.008	0.073	0.22	24	-0.18	8	32
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.029	0.24	0.42	2	-0.56	54	56
FOS	-0.033	0.22	0.36	5	-0.4	127	132
NRAS	0.04	0.01	-10000	0	0	30	30
mol:Ca2+	-0.001	0.079	0.18	8	-0.16	58	66
MAPK3	-0.01	0.19	0.36	5	-0.47	45	50
MAPK1	-0.024	0.2	0.37	4	-0.5	48	52
JAK2	-0.022	0.079	0.25	9	-0.24	6	15
NF2	0.004	0.075	-10000	0	-0.7	6	6
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.001	0.073	0.18	3	-0.17	69	72
NRG1	0.035	0.016	-10000	0	0	93	93
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
MAPK8	-0.019	0.11	0.22	5	-0.22	76	81
MAPK9	-0.011	0.071	0.2	23	-0.16	5	28
ERBB2	-0.024	0.041	0.26	10	-10000	0	10
ERBB3	0.033	0.018	-10000	0	0	124	124
SHC1	0.04	0.01	-10000	0	0	31	31
RAC1	0.039	0.01	-10000	0	0	34	34
apoptosis	0.005	0.027	0.18	1	-0.21	7	8
STAT3 (dimer)	-0.023	0.25	-10000	0	-0.88	42	42
RNF41	-0.017	0.016	0.047	11	-0.12	3	14
FRAP1	-0.014	0.007	0.012	13	-10000	0	13
RAC1-CDC42/GTP	-0.03	0.056	0.09	20	-0.14	41	61
ErbB2/ErbB2/HSP90 (dimer)	-0.024	0.015	0.017	4	-0.12	5	9
CHRNA1	0.006	0.15	0.36	4	-0.37	34	38
myelination	-0.01	0.097	0.26	32	-0.2	4	36
PPP3CB	-0.02	0.079	0.2	17	-0.19	5	22
KRAS	0.034	0.016	-10000	0	0	103	103
RAC1-CDC42/GDP	0.02	0.099	0.21	2	-0.17	67	69
NRG2	0.041	0.007	-10000	0	0	14	14
mol:GDP	-0.001	0.073	0.18	3	-0.17	68	71
SOS1	0.038	0.013	-10000	0	0	56	56
MAP2K2	-0.006	0.11	0.25	23	-0.23	42	65
SRC	0.039	0.01	-10000	0	0	36	36
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.021	0.085	0.24	13	-0.21	9	22
MAP2K1	-0.017	0.19	0.38	1	-0.51	33	34
heart morphogenesis	-0.001	0.079	0.18	8	-0.16	58	66
RAS family/GDP	0.025	0.1	0.27	2	-0.19	46	48
GRB2	0.041	0.007	-10000	0	0	17	17
PRKACA	0.008	0.084	-10000	0	-0.73	7	7
CHRNE	0.008	0.023	0.071	2	-10000	0	2
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	0.005	0.012	-10000	0	-0.021	29	29
nervous system development	-0.001	0.079	0.18	8	-0.16	58	66
CDC42	0.04	0.009	-10000	0	0	24	24

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.04	0.01	-10000	0	0	31	31
EGFR	0.037	0.014	-10000	0	0	72	72
EGF/EGFR	0.046	0.059	-10000	0	-0.099	55	55
EGF/EGFR dimer/SHC/GRB2/SOS1	0.081	0.077	-10000	0	-0.11	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.036	0.015	-10000	0	0	86	86
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.038	0.012	-10000	0	0	53	53
EGF/EGFR dimer/SHC	0.058	0.055	-10000	0	-0.12	33	33
mol:GDP	0.073	0.073	-10000	0	-0.11	49	49
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.035	0.016	-10000	0	0	99	99
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
HRAS/GTP	0.048	0.061	-10000	0	-0.11	49	49
SHC1	0.04	0.01	-10000	0	0	31	31
HRAS/GDP	0.069	0.073	-10000	0	-0.12	44	44
FRAP1	-0.016	0.073	0.2	40	-0.18	4	44
EGF/EGFR dimer	0.041	0.051	-10000	0	-0.13	37	37
SOS1	0.038	0.013	-10000	0	0	56	56
GRB2	0.041	0.007	-10000	0	0	17	17
ETA receptor/Endothelin-1	0.037	0.047	-10000	0	-0.14	25	25

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.039	0.011	-10000	0	0	38	38
RAS family/GTP/Tiam1	0.012	0.06	-10000	0	-0.16	38	38
NT3 (dimer)/TRKC	0.04	0.036	-10000	0	-0.14	8	8
NT3 (dimer)/TRKB	0.056	0.045	-10000	0	-0.12	10	10
SHC/Grb2/SOS1/GAB1/PI3K	-0.001	0.08	-10000	0	-0.19	63	63
RAPGEF1	0.04	0.008	-10000	0	0	23	23
BDNF	0.04	0.008	-10000	0	0	23	23
PIK3CA	0.03	0.019	-10000	0	0	155	155
DYNLT1	0.036	0.015	-10000	0	0	81	81
NTRK1	0.039	0.01	-10000	0	0	35	35
NTRK2	0.039	0.01	-10000	0	0	36	36
NTRK3	0.038	0.012	-10000	0	0	49	49
NT-4/5 (dimer)/TRKB	0.051	0.018	-10000	0	-0.088	1	1
neuron apoptosis	-0.03	0.1	0.25	33	-0.22	4	37
SHC 2-3/Grb2	0.031	0.11	0.24	3	-0.27	33	36
SHC1	0.04	0.01	-10000	0	0	31	31
SHC2	0.007	0.12	0.21	3	-0.37	41	44
SHC3	0.025	0.088	0.21	3	-0.38	17	20
STAT3 (dimer)	0.003	0.11	-10000	0	-0.27	75	75
NT3 (dimer)/TRKA	0.054	0.046	-10000	0	-0.12	10	10
RIN/GDP	0.047	0.086	0.23	23	-0.19	24	47
GIPC1	0.035	0.015	-10000	0	0	89	89
KRAS	0.034	0.016	-10000	0	0	103	103
DNAJA3	0.01	0.052	0.15	10	-0.15	13	23
RIN/GTP	0.029	0.008	-10000	0	-10000	0	0
CCND1	-0.048	0.17	-10000	0	-0.49	74	74
MAGED1	0.04	0.009	-10000	0	0	26	26
PTPN11	0.04	0.009	-10000	0	0	27	27
RICS	0.037	0.014	-10000	0	0	71	71
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.065	0.051	-10000	0	-0.13	26	26
GRB2	0.041	0.007	-10000	0	0	17	17
NGF (dimer)/TRKA/MATK	0.048	0.02	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.047	0.038	-10000	0	-0.14	15	15
ELMO1	0.035	0.015	-10000	0	0	87	87
RhoG/GTP/ELMO1/DOCK1	0.034	0.048	-10000	0	-0.11	44	44
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.04	0.01	-10000	0	0	31	31
DOCK1	0.037	0.013	-10000	0	0	62	62
GAB2	0.031	0.018	-10000	0	0	141	141
RIT2	0.039	0.01	-10000	0	0	37	37
RIT1	0.038	0.012	-10000	0	0	48	48
FRS2	0.039	0.011	-10000	0	0	40	40
DNM1	0.039	0.011	-10000	0	0	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	52	52
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.028	0.062	0.18	9	-0.15	15	24
mol:GDP	0.043	0.11	0.27	25	-0.27	25	50
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.022	0.03	-10000	0	-0.13	19	19
RIT1/GDP	0.043	0.084	0.23	17	-0.19	26	43
TIAM1	0.037	0.014	-10000	0	0	72	72
PIK3R1	0.034	0.017	-10000	0	0	108	108
BDNF (dimer)/TRKB	0.071	0.032	-10000	0	-0.12	1	1
KIDINS220/CRKL/C3G	0.056	0.018	-10000	0	-10000	0	0
SHC/RasGAP	0.048	0.038	-10000	0	-0.14	16	16
FRS2 family/SHP2	0.067	0.051	-10000	0	-0.12	29	29
SHC/GRB2/SOS1/GAB1	0.078	0.062	-10000	0	-0.12	32	32
RIT1/GTP	0.025	0.026	-10000	0	-0.13	15	15
NT3 (dimer)	0.031	0.018	-10000	0	0	147	147
RAP1/GDP	0.033	0.074	0.18	17	-0.17	28	45
KIDINS220/CRKL	0.039	0.011	-10000	0	0	38	38
BDNF (dimer)	0.04	0.008	-10000	0	0	23	23
ubiquitin-dependent protein catabolic process	0.042	0.033	-10000	0	-0.11	15	15
Schwann cell development	-0.007	0.011	-10000	0	-0.044	11	11
EHD4	0.039	0.011	-10000	0	0	38	38
FRS2 family/GRB2/SOS1	0.081	0.062	-10000	0	-0.12	33	33
FRS2 family/SHP2/CRK family/C3G/GAB2	0.005	0.084	-10000	0	-0.24	27	27
RAP1B	0.038	0.013	-10000	0	0	59	59
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.069	0.053	0.21	1	-0.11	9	10
ABL1	0.039	0.011	-10000	0	0	41	41
SH2B family/GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
Rap1/GTP	0.007	0.11	-10000	0	-0.33	27	27
STAT3	0.004	0.11	-10000	0	-0.27	75	75
axon guidance	0.047	0.041	-10000	0	-0.11	9	9
MAPK3	-0.008	0.047	0.19	28	-10000	0	28
MAPK1	-0.007	0.046	0.19	27	-10000	0	27
CDC42/GDP	0.049	0.087	0.23	25	-0.19	23	48
NTF3	0.031	0.018	-10000	0	0	147	147
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.048	0.022	-10000	0	-0.11	2	2
PI3K	0.024	0.061	-10000	0	-0.15	47	47
FRS3	0.04	0.008	-10000	0	0	23	23
FAIM	0.038	0.012	-10000	0	0	52	52
GAB1	0.038	0.012	-10000	0	0	52	52
RASGRF1	0.01	0.053	0.15	10	-0.16	13	23
SOS1	0.038	0.013	-10000	0	0	56	56
MCF2L	0.005	0.061	0.18	41	-0.12	8	49
RGS19	0.036	0.015	-10000	0	0	78	78
CDC42	0.04	0.009	-10000	0	0	24	24
RAS family/GTP	0.035	0.12	0.3	3	-0.34	30	33
Rac1/GDP	0.048	0.087	0.23	26	-0.19	23	49
NGF (dimer)/TRKA/GRIT	0.042	0.036	-10000	0	-0.11	20	20
neuron projection morphogenesis	-0.052	0.25	-10000	0	-0.84	43	43
NGF (dimer)/TRKA/NEDD4-2	0.043	0.033	-10000	0	-0.11	15	15
MAP2K1	-0.011	0.072	0.19	48	-0.19	3	51
NGFR	0.04	0.009	-10000	0	0	28	28
NGF (dimer)/TRKA/GIPC/GAIP	0.015	0.04	-10000	0	-0.14	25	25
RAS family/GTP/PI3K	-0.004	0.072	-10000	0	-0.19	52	52
FRS2 family/SHP2/GRB2/SOS1	0.09	0.076	-10000	0	-0.13	43	43
NRAS	0.04	0.009	-10000	0	0	30	30
GRB2/SOS1	0.047	0.047	-10000	0	-0.14	28	28
PRKCI	0.027	0.02	-10000	0	0	197	197
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCZ	0.042	0	-10000	0	-10000	0	0
MAPKKK cascade	0.026	0.047	-10000	0	-0.5	2	2
RASA1	0.037	0.014	-10000	0	0	71	71
TRKA/c-Abl	0.052	0.033	-10000	0	-0.14	11	11
SQSTM1	0.038	0.012	-10000	0	0	49	49
BDNF (dimer)/TRKB/GIPC	0.071	0.059	-10000	0	-0.11	21	21
NGF (dimer)/TRKA/p62/Atypical PKCs	0.048	0.069	-10000	0	-0.11	52	52
MATK	0.038	0.013	-10000	0	0	59	59
NEDD4L	0.036	0.015	-10000	0	0	79	79
RAS family/GDP	-0.009	0.038	-10000	0	-0.14	26	26
NGF (dimer)/TRKA	0.015	0.052	0.16	6	-0.16	14	20
Rac1/GTP	-0.003	0.048	-10000	0	-0.14	25	25
FRS2 family/SHP2/CRK family	0.088	0.069	-10000	0	-0.11	26	26

×

Arf6 downstream 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
PLAUR	-0.028	0.2	-10000	0	-0.81	35	35
regulation of axonogenesis	-0.002	0.051	0.21	23	-10000	0	23
myoblast fusion	-0.011	0.1	0.35	38	-10000	0	38
mol:GTP	0.017	0.067	-10000	0	-0.2	46	46
regulation of calcium-dependent cell-cell adhesion	-0.034	0.089	0.2	43	-10000	0	43
ARF1/GTP	0.038	0.06	-10000	0	-0.16	42	42
mol:GM1	0.003	0.047	-10000	0	-0.15	46	46
mol:Choline	0.001	0.04	0.093	1	-0.16	28	29
lamellipodium assembly	-0.013	0.12	-10000	0	-0.4	46	46
MAPK3	0.01	0.085	-10000	0	-0.28	41	41
ARF6/GTP/NME1/Tiam1	0.035	0.09	-10000	0	-0.2	43	43
ARF1	0.038	0.012	-10000	0	0	50	50
ARF6/GDP	0.011	0.1	-10000	0	-0.35	38	38
ARF1/GDP	0.014	0.1	-10000	0	-0.31	44	44
ARF6	0.042	0.046	-10000	0	-0.13	35	35
RAB11A	0.04	0.009	-10000	0	0	24	24
TIAM1	0.032	0.023	-10000	0	-0.046	29	29
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.079	-10000	0	-0.28	35	35
actin filament bundle formation	-0.025	0.11	0.31	48	-10000	0	48
KALRN	0.003	0.075	-10000	0	-0.26	38	38
RAB11FIP3/RAB11A	0.058	0.023	-10000	0	-0.14	6	6
RhoA/GDP	0.026	0.11	-10000	0	-0.31	48	48
NME1	0.031	0.024	-10000	0	-0.012	121	121
Rac1/GDP	0.025	0.11	-10000	0	-0.31	47	47
substrate adhesion-dependent cell spreading	0.017	0.067	-10000	0	-0.2	46	46
cortical actin cytoskeleton organization	-0.013	0.12	-10000	0	-0.41	46	46
RAC1	0.039	0.01	-10000	0	0	34	34
liver development	0.017	0.067	-10000	0	-0.2	46	46
ARF6/GTP	0.017	0.067	-10000	0	-0.2	46	46
RhoA/GTP	0.041	0.063	-10000	0	-0.16	46	46
mol:GDP	-0.004	0.098	-10000	0	-0.35	39	39
ARF6/GTP/RAB11FIP3/RAB11A	0.061	0.067	-10000	0	-0.14	51	51
RHOA	0.041	0.007	-10000	0	0	14	14
PLD1	0.008	0.049	-10000	0	-0.17	32	32
RAB11FIP3	0.042	0.003	-10000	0	0	3	3
tube morphogenesis	-0.013	0.12	-10000	0	-0.4	46	46
ruffle organization	0.002	0.051	-10000	0	-0.21	23	23
regulation of epithelial cell migration	0.017	0.067	-10000	0	-0.2	46	46
PLD2	0.015	0.049	-10000	0	-0.15	40	40
PIP5K1A	0.002	0.052	-10000	0	-0.21	23	23
mol:Phosphatidic acid	0.001	0.04	0.093	1	-0.16	28	29
Rac1/GTP	-0.014	0.12	-10000	0	-0.41	46	46

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.025	0.12	0.25	3	-0.31	27	30
CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
AKT1	0.039	0.01	-10000	0	0	37	37
AKT2	0.038	0.012	-10000	0	0	47	47
STXBP4	0.038	0.012	-10000	0	0	47	47
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.013	0.12	0.24	5	-0.32	28	33
YWHAZ	0.034	0.016	-10000	0	0	102	102
CALM1	0.04	0.01	-10000	0	0	31	31
YWHAQ	0.04	0.009	-10000	0	0	28	28
TBC1D4	-0.018	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.037	0.013	-10000	0	0	60	60
YWHAB	0.038	0.012	-10000	0	0	52	52
SNARE/Synip	0.045	0.029	-10000	0	-0.11	9	9
YWHAG	0.04	0.009	-10000	0	0	25	25
ASIP	0.037	0.013	-10000	0	0	60	60
PRKCI	0.027	0.02	-10000	0	0	197	197
AS160/CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
RHOQ	0.039	0.01	-10000	0	0	33	33
GYS1	0.009	0.029	0.25	4	-0.17	6	10
PRKCZ	0.042	0	-10000	0	-10000	0	0
TRIP10	0.038	0.012	-10000	0	0	47	47
TC10/GTP/CIP4/Exocyst	0.047	0.029	-10000	0	-0.11	12	12
AS160/14-3-3	0.021	0.081	0.21	1	-0.25	23	24
VAMP2	0.037	0.014	-10000	0	0	67	67
SLC2A4	0.011	0.13	0.24	4	-0.36	28	32
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.024	0.025	-10000	0	-0.2	6	6
SFN	0.036	0.015	-10000	0	0	86	86
LNPEP	0.036	0.015	-10000	0	0	86	86
YWHAE	0.038	0.013	-10000	0	0	58	58

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.04	0.009	-10000	0	0	25	25
MKNK1	0.04	0.009	-10000	0	0	25	25
mol:PIP3	-0.013	0.038	0.2	1	-0.16	15	16
FRAP1	0.028	0.1	-10000	0	-0.43	22	22
AKT1	0.018	0.081	0.17	100	-0.17	10	110
INSR	0.038	0.012	-10000	0	0	53	53
Insulin Receptor/Insulin	0.048	0.023	-10000	0	-0.11	4	4
mol:GTP	0.051	0.088	0.23	28	-0.16	11	39
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.052	-10000	0	-0.19	29	29
TSC2	0.039	0.01	-10000	0	0	35	35
RHEB/GDP	0.029	0.068	0.16	6	-0.16	14	20
TSC1	0.04	0.009	-10000	0	0	28	28
Insulin Receptor/IRS1	0.034	0.033	-10000	0	-0.23	7	7
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.012	0.071	-10000	0	-0.22	26	26
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.029	0.11	0.25	17	-0.31	28	45
MAP3K5	-0.009	0.066	0.2	5	-0.22	46	51
PIK3R1	0.034	0.017	-10000	0	0	108	108
apoptosis	-0.009	0.066	0.2	5	-0.22	46	51
mol:LY294002	0	0	0.001	4	-0.001	6	10
EIF4B	0.024	0.1	0.26	14	-0.29	28	42
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.037	0.098	0.23	14	-0.27	27	41
eIF4E/eIF4G1/eIF4A1	0.012	0.062	-10000	0	-0.27	20	20
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.028	0.053	-10000	0	-0.16	16	16
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.075	0.2	21	-0.18	24	45
FKBP1A	0.039	0.012	-10000	0	0	50	50
RHEB/GTP	0.052	0.084	0.22	18	-0.16	13	31
mol:Amino Acids	0	0	0.001	4	-0.001	6	10
FKBP12/Rapamycin	0.028	0.013	-10000	0	-0.13	2	2
PDPK1	0.006	0.075	0.16	91	-0.17	11	102
EIF4E	0.039	0.011	-10000	0	0	43	43
ASK1/PP5C	0.013	0.2	-10000	0	-0.56	52	52
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.001	0.12	-10000	0	-0.46	20	20
TSC1/TSC2	0.057	0.095	0.25	28	-0.18	10	38
tumor necrosis factor receptor activity	0	0	0.001	6	-0.001	4	10
RPS6	0.039	0.011	-10000	0	0	41	41
PPP5C	0.04	0.01	-10000	0	0	32	32
EIF4G1	0.032	0.018	-10000	0	0	129	129
IRS1	0.01	0.03	-10000	0	-0.24	7	7
INS	0.04	0.009	-10000	0	0	30	30
PTEN	0.039	0.011	-10000	0	0	38	38
PDK2	0.006	0.073	0.16	86	-0.17	10	96
EIF4EBP1	-0.053	0.3	-10000	0	-1.1	46	46
PIK3CA	0.03	0.019	-10000	0	0	155	155
PPP2R5D	0.03	0.1	0.28	6	-0.38	22	28
peptide biosynthetic process	-0.014	0.032	0.19	11	-10000	0	11
RHEB	0.037	0.013	-10000	0	0	64	64
EIF4A1	0.039	0.011	-10000	0	0	39	39
mol:Rapamycin	0	0.001	0.004	39	-0.002	4	43
EEF2	-0.014	0.032	0.19	11	-10000	0	11
eIF4E/4E-BP1	-0.032	0.29	-10000	0	-0.98	46	46

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.018	0.015	0.058	14	-10000	0	14
SNTA1	0.039	0.011	-10000	0	0	44	44
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.018	0.016	0.058	14	-10000	0	14
MAPK12	-0.008	0.044	0.21	7	-0.16	17	24
CCND1	-0.038	0.13	-10000	0	-0.37	72	72
p38 gamma/SNTA1	0.023	0.071	0.22	12	-0.17	31	43
MAP2K3	0.038	0.012	-10000	0	0	47	47
PKN1	0.035	0.016	-10000	0	0	99	99
G2/M transition checkpoint	-0.008	0.043	0.21	7	-0.16	17	24
MAP2K6	0.004	0.047	0.24	6	-0.17	22	28
MAPT	0	0.054	0.15	17	-0.19	16	33
MAPK13	-0.017	0.008	0	98	-10000	0	98
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.003	0.05	-10000	0	-0.2	32	32

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.019	0.053	-10000	0	-0.11	63	63
TRAF2/ASK1	0.044	0.035	-10000	0	-0.11	20	20
ATM	0.036	0.014	-10000	0	0	73	73
MAP2K3	-0.041	0.16	-10000	0	-0.32	105	105
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.043	0.14	0.21	2	-0.32	79	81
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.037	0.013	-10000	0	0	61	61
TXN	0.009	0.003	-10000	0	-10000	0	0
CALM1	0.04	0.01	-10000	0	0	31	31
GADD45A	0.036	0.014	-10000	0	0	73	73
GADD45B	0.035	0.016	-10000	0	0	99	99
MAP3K1	0.036	0.014	-10000	0	0	77	77
MAP3K6	0.04	0.008	-10000	0	0	22	22
MAP3K7	0.038	0.012	-10000	0	0	47	47
MAP3K4	0.038	0.012	-10000	0	0	49	49
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.048	0.041	-10000	0	-0.14	20	20
TAK1/TAB family	0.017	0.067	0.17	6	-0.25	24	30
RAC1/OSM/MEKK3	0.072	0.026	-10000	0	-0.11	1	1
TRAF2	0.04	0.009	-10000	0	0	29	29
RAC1/OSM/MEKK3/MKK3	-0.009	0.14	-10000	0	-0.28	92	92
TRAF6	0.01	0.041	-10000	0	-0.2	21	21
RAC1	0.039	0.01	-10000	0	0	34	34
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.041	0.007	-10000	0	0	18	18
CCM2	0.041	0.007	-10000	0	0	17	17
CaM/Ca2+/CAMKIIB	0.051	0.019	-10000	0	-0.11	3	3
MAPK11	0.031	0.018	-10000	0	0	142	142
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.062	0.044	-10000	0	-0.1	22	22
OSM/MEKK3	0.059	0.014	-10000	0	-10000	0	0
TAOK1	0.003	0.054	-10000	0	-0.2	38	38
TAOK2	0.004	0.053	-10000	0	-0.2	36	36
TAOK3	0	0.059	-10000	0	-0.2	46	46
MAP3K7IP1	0.038	0.012	-10000	0	0	54	54
MAPK14	0.04	0.009	-10000	0	0	28	28
MAP3K7IP2	0.038	0.013	-10000	0	0	59	59
MAP3K5	0.037	0.014	-10000	0	0	69	69
MAP3K10	0.039	0.011	-10000	0	0	41	41
MAP3K3	0.041	0.007	-10000	0	0	17	17
TRX/ASK1	0.023	0.046	0.11	1	-0.15	33	34
GADD45/MTK1/MTK1	0.055	0.069	-10000	0	-0.11	58	58

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.042	0.041	0.17	3	-0.15	11	14
BIRC5	0.037	0.013	-10000	0	0	60	60
NFKBIA	-0.004	0.028	0.25	1	-0.18	6	7
CPEB1	0.039	0.01	-10000	0	0	34	34
AKT1	-0.003	0.042	0.26	9	-0.18	7	16
NDEL1	0.039	0.011	-10000	0	0	38	38
Aurora A/BRCA1	0.027	0.05	0.15	3	-0.1	53	56
NDEL1/TACC3	0.045	0.051	0.17	2	-0.11	30	32
GADD45A	0.036	0.014	-10000	0	0	73	73
GSK3B	0.039	0.012	0.091	15	0	26	41
PAK1/Aurora A	0.042	0.042	0.17	3	-0.16	10	13
MDM2	0.039	0.01	-10000	0	0	35	35
JUB	0.037	0.013	-10000	0	0	60	60
TPX2	-0.015	0.009	-10000	0	-10000	0	0
TP53	-0.046	0.12	0.16	2	-0.24	142	144
DLG7	-0.002	0.025	0.25	1	-0.17	3	4
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.04	0.009	-10000	0	0	27	27
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.048	0.054	0.18	2	-0.12	30	32
G2/M transition of mitotic cell cycle	0.026	0.049	0.15	3	-0.1	53	56
AURKA	0.01	0.03	0.13	13	-0.2	7	20
AURKB	0	0.063	-10000	0	-0.2	45	45
CDC25B	0.005	0.045	-10000	0	-0.22	18	18
G2/M transition checkpoint	0.033	0.044	0.15	3	-0.11	31	34
mRNA polyadenylation	0.039	0.035	0.15	2	-0.14	10	12
Aurora A/CPEB	0.039	0.036	0.15	2	-0.14	10	12
Aurora A/TACC1/TRAP/chTOG	0.055	0.075	0.21	2	-0.18	14	16
BRCA1	0.034	0.016	-10000	0	0	106	106
centrosome duplication	0.042	0.041	0.17	3	-0.16	10	13
regulation of centrosome cycle	0.044	0.05	0.17	2	-0.11	30	32
spindle assembly	0.053	0.074	0.21	2	-0.17	14	16
TDRD7	0.035	0.016	-10000	0	0	92	92
Aurora A/RasGAP/Survivin	0.044	0.073	0.2	5	-0.14	13	18
CENPA	0.008	0.055	-10000	0	-0.33	12	12
Aurora A/PP2A	0.046	0.039	0.17	3	-0.15	10	13
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.013	0.06	0.15	9	-0.2	17	26
negative regulation of DNA binding	-0.045	0.12	0.16	2	-0.24	142	144
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.057	0.018	-10000	0	-10000	0	0
RASA1	0.037	0.014	-10000	0	0	71	71
Ajuba/Aurora A	0.034	0.044	0.15	3	-0.11	31	34
mitotic prometaphase	0.003	0.025	0.074	62	-10000	0	62
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.03	0.13	13	-0.2	7	20
TACC1	0.035	0.016	-10000	0	0	93	93
TACC3	0.034	0.017	-10000	0	0	112	112
Aurora A/Antizyme1	0.029	0.044	0.15	2	-0.1	36	38
Aurora A/RasGAP	0.042	0.042	0.17	3	-0.16	10	13
OAZ1	0.034	0.017	-10000	0	0	107	107
RAN	0.041	0.006	-10000	0	0	13	13
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.034	0.017	0.091	14	0	89	103
GIT1	0.04	0.009	-10000	0	0	27	27
GIT1/beta-PIX/PAK1	0.066	0.044	-10000	0	-0.12	15	15
Importin alpha/Importin beta/TPX2	-0.015	0.009	-10000	0	-10000	0	0
PPP2R5D	0.04	0.009	-10000	0	0	29	29
Aurora A/TPX2	0.018	0.037	0.15	2	-0.19	9	11
PAK1	0.037	0.014	-10000	0	0	70	70
CKAP5	0.039	0.011	-10000	0	0	45	45

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.061	0.1	0.29	21	-0.31	9	30
PDGFB-D/PDGFRB/SLAP	0.032	0.038	-10000	0	-0.14	10	10
PDGFB-D/PDGFRB/APS/CBL	0.048	0.024	-10000	0	-0.11	4	4
AKT1	0.024	0.11	0.26	43	-0.18	1	44
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.045	0.094	0.27	18	-0.33	10	28
PIK3CA	0.03	0.019	-10000	0	0	155	155
FGR	0.023	0.092	0.26	11	-0.39	13	24
mol:Ca2+	0.027	0.087	0.25	15	-0.36	10	25
MYC	0.004	0.28	0.4	9	-0.67	74	83
SHC1	0.04	0.01	-10000	0	0	31	31
HRAS/GDP	0.038	0.059	0.19	43	-0.11	17	60
LRP1/PDGFRB/PDGFB	0.055	0.057	-10000	0	-0.12	36	36
GRB10	0.04	0.008	-10000	0	0	23	23
PTPN11	0.04	0.009	-10000	0	0	27	27
GO:0007205	0.026	0.088	0.26	14	-0.37	10	24
PTEN	0.039	0.011	-10000	0	0	38	38
GRB2	0.041	0.007	-10000	0	0	17	17
GRB7	0.037	0.013	-10000	0	0	63	63
PDGFB-D/PDGFRB/SHP2	0.047	0.043	-10000	0	-0.14	22	22
PDGFB-D/PDGFRB/GRB10	0.051	0.034	-10000	0	-0.15	9	9
cell cycle arrest	0.032	0.038	-10000	0	-0.14	10	10
HRAS	0.04	0.01	-10000	0	0	31	31
HIF1A	0.01	0.096	0.24	41	-0.2	6	47
GAB1	0.023	0.1	0.28	8	-0.3	15	23
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.025	0.11	0.29	20	-0.28	14	34
PDGFB-D/PDGFRB	0.057	0.052	-10000	0	-0.13	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.048	0.042	-10000	0	-0.14	22	22
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.054	0.12	0.33	15	-0.26	30	45
positive regulation of MAPKKK cascade	0.047	0.043	-10000	0	-0.14	22	22
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	0.027	0.088	0.26	14	-0.37	10	24
E5	0	0.002	-10000	0	-10000	0	0
CSK	0.04	0.009	-10000	0	-0.003	23	23
PDGFB-D/PDGFRB/GRB7	0.047	0.034	-10000	0	-0.14	8	8
SHB	0.041	0.007	-10000	0	0	17	17
BLK	-0.036	0.16	0.3	4	-0.36	96	100
PTPN2	0.039	0.015	-10000	0	-0.014	36	36
PDGFB-D/PDGFRB/SNX15	0.054	0.025	-10000	0	-0.14	3	3
BCAR1	0.036	0.014	-10000	0	0	76	76
VAV2	0.01	0.13	0.3	9	-0.34	37	46
CBL	0.04	0.008	-10000	0	0	23	23
PDGFB-D/PDGFRB/DEP1	0.047	0.04	-10000	0	-0.14	19	19
LCK	0.028	0.079	0.27	8	-0.38	6	14
PDGFRB	0.036	0.019	-10000	0	-0.007	81	81
ACP1	0.04	0.009	-10000	0	0	26	26
HCK	0.016	0.095	0.3	4	-0.46	13	17
ABL1	0.019	0.091	0.24	19	-0.25	14	33
PDGFB-D/PDGFRB/CBL	0.023	0.1	0.27	8	-0.37	11	19
PTPN1	0.036	0.017	-10000	0	-0.007	70	70
SNX15	0.041	0.005	-10000	0	0	7	7
STAT3	0.038	0.013	-10000	0	0	56	56
STAT1	0.034	0.017	-10000	0	0	108	108
cell proliferation	0.012	0.26	0.34	18	-0.6	74	92
SLA	0.027	0.02	-10000	0	0	206	206
actin cytoskeleton reorganization	0.01	0.095	0.22	78	-0.18	1	79
SRC	0.026	0.058	0.32	3	-10000	0	3
PI3K	-0.027	0.036	-10000	0	-0.12	31	31
PDGFB-D/PDGFRB/GRB7/SHC	0.063	0.042	-10000	0	-0.12	8	8
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.046	0.096	0.28	18	-0.34	10	28
LYN	0.001	0.12	0.3	4	-0.44	31	35
LRP1	0.036	0.014	-10000	0	0	75	75
SOS1	0.038	0.013	-10000	0	0	56	56
STAT5B	0.039	0.011	-10000	0	0	43	43
STAT5A	0.038	0.012	-10000	0	0	51	51
NCK1-2/p130 Cas	0.075	0.075	-10000	0	-0.12	18	18
SPHK1	0.042	0.009	-10000	0	0	20	20
EDG1	0.042	0.007	-10000	0	0	12	12
mol:DAG	0.027	0.088	0.26	14	-0.37	10	24
PLCG1	0.027	0.09	0.26	14	-0.38	10	24
NHERF/PDGFRB	0.061	0.047	-10000	0	-0.12	17	17
YES1	0.003	0.12	0.26	5	-0.42	33	38
cell migration	0.059	0.047	-10000	0	-0.12	17	17
SHC/Grb2/SOS1	0.083	0.073	-10000	0	-0.13	24	24
SLC9A3R2	0.038	0.012	-10000	0	0	53	53
SLC9A3R1	0.038	0.012	-10000	0	0	49	49
NHERF1-2/PDGFRB/PTEN	0.079	0.057	-10000	0	-0.12	25	25
FYN	-0.014	0.14	0.28	3	-0.38	55	58
DOK1	0.006	0.069	0.19	56	-10000	0	56
HRAS/GTP	0.029	0.01	-10000	0	-0.13	1	1
PDGFB	0.038	0.013	-10000	0	0	57	57
RAC1	-0.032	0.24	0.3	10	-0.56	72	82
PRKCD	0.004	0.068	0.2	51	-10000	0	51
FER	0.004	0.066	0.19	49	-10000	0	49
MAPKKK cascade	-0.002	0.08	0.18	64	-0.18	4	68
RASA1	0.003	0.064	0.19	45	-0.2	1	46
NCK1	0.036	0.015	-10000	0	0	80	80
NCK2	0.042	0.004	-10000	0	0	6	6
p62DOK/Csk	0.056	0.056	0.2	58	-0.11	11	69
PDGFB-D/PDGFRB/SHB	0.053	0.026	-10000	0	-0.14	3	3
chemotaxis	0.02	0.09	0.24	19	-0.25	14	33
STAT1-3-5/STAT1-3-5	0.05	0.08	-10000	0	-0.14	22	22
Bovine Papilomavirus E5/PDGFRB	0.026	0.019	-10000	0	-0.077	6	6
PTPRJ	0.039	0.01	-10000	0	0	35	35

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.039	0.011	-10000	0	0	41	41
VLDLR	0.032	0.018	-10000	0	0	129	129
LRPAP1	0.036	0.015	-10000	0	0	78	78
NUDC	0.04	0.009	-10000	0	0	26	26
RELN/LRP8	0.049	0.055	-10000	0	-0.12	28	28
CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
KATNA1	0.037	0.013	-10000	0	0	61	61
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.001	0.068	0.21	35	-0.19	1	36
IQGAP1/CaM	0.041	0.056	-10000	0	-0.14	45	45
DAB1	0.04	0.009	-10000	0	0	27	27
IQGAP1	0.037	0.014	-10000	0	0	69	69
PLA2G7	0.03	0.019	-10000	0	0	157	157
CALM1	0.04	0.01	-10000	0	0	31	31
DYNLT1	0.036	0.015	-10000	0	0	81	81
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.041	0.053	-10000	0	-0.14	36	36
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.04	0.009	-10000	0	0	30	30
LIS1/Poliovirus Protein 3A	-0.015	0.013	-10000	0	-0.13	5	5
CDK5R2	0.041	0.006	-10000	0	0	11	11
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.043	0.059	-10000	0	-0.12	37	37
YWHAE	0.038	0.013	-10000	0	0	58	58
NDEL1/14-3-3 E	0.035	0.084	0.28	26	-0.17	7	33
MAP1B	-0.002	0.049	0.18	3	-0.19	34	37
RAC1	0.012	0.043	0.12	25	-0.59	1	26
p35/CDK5	-0.006	0.071	0.19	37	-0.18	1	38
RELN	0.034	0.017	-10000	0	0	110	110
PAFAH/LIS1	0.024	0.027	-10000	0	-0.15	5	5
LIS1/CLIP170	-0.015	0.013	-10000	0	-0.13	5	5
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.024	0.079	0.2	16	-0.19	13	29
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.001	0.096	-10000	0	-0.2	85	85
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.007	0.081	0.21	51	-0.16	4	55
LIS1/IQGAP1	0.03	0.026	-10000	0	-0.15	5	5
RHOA	0.012	0.044	-10000	0	-0.45	2	2
PAFAH1B1	-0.017	0.008	-10000	0	-10000	0	0
PAFAH1B3	0.035	0.016	-10000	0	0	92	92
PAFAH1B2	0.04	0.01	-10000	0	0	31	31
MAP1B/LIS1/Dynein heavy chain	0.012	0.061	0.18	1	-0.15	38	39
NDEL1/Katanin 60/Dynein heavy chain	0.043	0.093	0.29	24	-0.18	11	35
LRP8	0.039	0.011	-10000	0	0	39	39
NDEL1/Katanin 60	0.033	0.084	0.27	27	-0.17	11	38
P39/CDK5	-0.006	0.073	0.19	39	-0.18	1	40
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0.025	-10000	0	-0.15	5	5
CDK5	-0.01	0.054	0.19	20	-0.19	1	21
PPP2R5D	0.04	0.009	-10000	0	0	29	29
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.012	0.011	-10000	0	-0.11	5	5
CSNK2A1	0.038	0.012	-10000	0	0	54	54
RELN/VLDLR/DAB1/LIS1	0.056	0.065	0.2	20	-0.11	33	53
RELN/VLDLR	0.053	0.073	-10000	0	-0.11	58	58
CDC42	0.012	0.049	-10000	0	-0.45	3	3

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.023	0.13	0.25	3	-0.36	46	49
BAG4	0.037	0.013	-10000	0	0	64	64
BAD	-0.008	0.048	0.17	5	-0.14	31	36
NFKBIA	0.037	0.014	-10000	0	0	66	66
BIRC3	0.026	0.02	-10000	0	0	218	218
BAX	-0.007	0.047	0.14	8	-0.14	28	36
EnzymeConsortium:3.1.4.12	-0.003	0.032	0.074	3	-0.084	39	42
IKBKB	-0.024	0.13	0.23	11	-0.35	43	54
MAP2K2	-0.01	0.04	0.15	3	-0.14	9	12
MAP2K1	-0.012	0.045	0.17	8	-0.15	9	17
SMPD1	-0.003	0.037	0.097	1	-0.1	38	39
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.014	0.14	0.25	10	-0.36	46	56
MAP2K4	-0.01	0.041	0.14	1	-0.13	25	26
protein ubiquitination	-0.029	0.13	0.24	2	-0.36	46	48
EnzymeConsortium:2.7.1.37	-0.013	0.044	0.15	4	-0.15	9	13
response to UV	0	0	0.002	7	-0.002	4	11
RAF1	-0.01	0.044	0.14	5	-0.13	23	28
CRADD	0.041	0.006	-10000	0	0	13	13
mol:ceramide	-0.004	0.047	0.12	2	-0.13	38	40
I-kappa-B-alpha/RELA/p50/ubiquitin	0.042	0.044	-10000	0	-0.11	37	37
MADD	0.041	0.006	-10000	0	0	11	11
MAP3K1	-0.008	0.044	0.11	2	-0.13	39	41
TRADD	0.036	0.014	-10000	0	0	76	76
RELA/p50	0.041	0.006	-10000	0	0	10	10
MAPK3	-0.008	0.045	0.17	3	-0.16	11	14
MAPK1	-0.012	0.052	0.16	4	-0.16	24	28
p50/RELA/I-kappa-B-alpha	0.045	0.051	-10000	0	-0.14	37	37
FADD	-0.018	0.14	0.24	10	-0.36	45	55
KSR1	-0.007	0.042	0.12	1	-0.13	26	27
MAPK8	-0.016	0.043	0.17	3	-0.14	12	15
TRAF2	0.04	0.009	-10000	0	0	29	29
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.032	0.13	0.23	3	-0.35	48	51
TNF R/SODD	0.044	0.038	-10000	0	-0.13	14	14
TNF	0.04	0.009	-10000	0	0	26	26
CYCS	-0.007	0.049	0.14	4	-0.14	22	26
IKBKG	-0.03	0.13	0.23	3	-0.36	42	45
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.018	0.14	-10000	0	-0.38	45	45
RELA	0.041	0.006	-10000	0	0	10	10
RIPK1	0.038	0.012	-10000	0	0	48	48
AIFM1	-0.006	0.047	0.12	8	-0.14	22	30
TNF/TNF R/SODD	0.059	0.046	-10000	0	-0.12	15	15
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.019	0.13	-10000	0	-0.65	19	19
NSMAF	-0.015	0.14	0.25	15	-0.37	43	58
response to hydrogen peroxide	0	0	0.002	7	-0.002	4	11
BCL2	0.036	0.014	-10000	0	0	76	76

×

Syndecan-3-mediated signaling 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
CTTN	0.039	0.01	-9999	0	34	34
Syndecan-3/Src/Cortactin	0.026	0.094	-9999	-0.38	13	13
Syndecan-3/Neurocan	0.002	0.066	-9999	-0.42	13	13
POMC	0.041	0.007	-9999	0	17	17
EGFR	0.037	0.014	-9999	0	72	72
Syndecan-3/EGFR	0.03	0.074	-9999	-0.42	13	13
AGRP	0.036	0.014	-9999	0	76	76
NCSTN	0.04	0.009	-9999	0	24	24
PSENEN	0.035	0.016	-9999	0	92	92
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.036	0.015	-9999	0	83	83
APH1A	0.041	0.006	-9999	0	10	10
NCAN	0	0	-9999	-10000	0	0
long-term memory	0.038	0.081	-9999	-0.39	13	13
Syndecan-3/IL8	0.023	0.074	-9999	-0.42	13	13
PSEN1	0.039	0.01	-9999	0	35	35
Src/Cortactin	0.052	0.032	-9999	-0.14	10	10
FYN	0.034	0.016	-9999	0	103	103
limb bud formation	0.003	0.068	-9999	-0.43	13	13
MC4R	0	0	-9999	-10000	0	0
SRC	0.039	0.01	-9999	0	36	36
PTN	0.023	0.021	-9999	0	253	253
FGFR/FGF/Syndecan-3	0.003	0.069	-9999	-0.43	13	13
neuron projection morphogenesis	-0.013	0.072	-9999	-0.37	13	13
Syndecan-3/AgRP	0.03	0.074	-9999	-0.42	13	13
Syndecan-3/AgRP/MC4R	0.028	0.071	-9999	-0.41	13	13
Fyn/Cortactin	0.037	0.055	-9999	-0.14	44	44
SDC3	0.003	0.07	-9999	-0.44	13	13
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.023	0.073	-9999	-0.42	13	13
IL8	0.032	0.018	-9999	0	139	139
Syndecan-3/Fyn/Cortactin	0.04	0.082	-9999	-0.4	13	13
Syndecan-3/CASK	0.002	0.066	-9999	-0.42	13	13
alpha-MSH/MC4R	0.03	0.005	-9999	-10000	0	0
Gamma Secretase	0.073	0.087	-9999	-0.12	66	66

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.037	0.016	0.079	1	-0.057	3	4
HSPA8	0.039	0.01	-10000	0	0	34	34
SMAD3/SMAD4/ER alpha	0.065	0.092	0.26	11	-0.15	29	40
AKT1	0.04	0.017	-10000	0	-0.098	5	5
GSC	0.008	0.096	-10000	0	-0.95	3	3
NKX2-5	0.039	0.017	-10000	0	-0.018	38	38
muscle cell differentiation	-0.04	0.11	0.25	28	-10000	0	28
SMAD2-3/SMAD4/SP1	0.072	0.12	-10000	0	-0.19	15	15
SMAD4	0.036	0.046	-10000	0	-0.096	18	18
CBFB	0.036	0.015	-10000	0	0	82	82
SAP18	0.039	0.01	-10000	0	0	34	34
Cbp/p300/MSG1	0.06	0.056	-10000	0	-0.14	26	26
SMAD3/SMAD4/VDR	0.074	0.1	-10000	0	-0.2	16	16
MYC	0.021	0.022	0.12	4	-0.044	2	6
CDKN2B	-0.044	0.16	-10000	0	-0.92	9	9
AP1	0.004	0.092	-10000	0	-0.23	38	38
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.001	0.13	0.2	3	-0.31	54	57
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.012	0.063	-10000	0	-0.2	35	35
SP3	0.037	0.024	0.08	2	-0.038	47	49
CREB1	0.041	0.008	-10000	0	0	19	19
FOXH1	0.041	0.019	-10000	0	-0.059	17	17
SMAD3/SMAD4/GR	0.054	0.079	-10000	0	-0.14	35	35
GATA3	0.042	0.012	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	0.004	0.096	0.17	6	-0.27	37	43
MEF2C/TIF2	0.023	0.068	0.26	6	-0.21	17	23
endothelial cell migration	-0.031	0.1	0.91	5	-10000	0	5
MAX	0.029	0.027	0.098	3	-0.036	78	81
RBBP7	0.04	0.009	-10000	0	0	26	26
RBBP4	0.038	0.012	-10000	0	0	46	46
RUNX2	0.039	0.011	-10000	0	0	45	45
RUNX3	0.039	0.01	-10000	0	0	33	33
RUNX1	0.039	0.01	-10000	0	0	33	33
CTBP1	0.038	0.013	-10000	0	0	56	56
NR3C1	0.027	0.028	0.098	3	-0.036	78	81
VDR	0.038	0.013	-10000	0	0	56	56
CDKN1A	0.012	0.076	-10000	0	-0.61	3	3
KAT2B	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.081	0.06	-10000	0	-0.18	5	5
DCP1A	0.04	0.008	-10000	0	0	20	20
SKI	0.042	0.003	-10000	0	0	3	3
SERPINE1	0.03	0.1	-10000	0	-0.92	5	5
SMAD3/SMAD4/ATF2	0.064	0.075	-10000	0	-0.14	23	23
SMAD3/SMAD4/ATF3	0.061	0.068	-10000	0	-0.13	17	17
SAP30	0.038	0.012	-10000	0	0	55	55
Cbp/p300/PIAS3	0.061	0.059	-10000	0	-0.14	29	29
JUN	-0.002	0.087	0.19	3	-0.24	36	39
SMAD3/SMAD4/IRF7	0.071	0.071	-10000	0	-0.14	9	9
TFE3	0.038	0.033	0.11	1	-0.081	37	38
COL1A2	-0.091	0.26	-10000	0	-0.62	103	103
mesenchymal cell differentiation	-0.064	0.07	0.13	16	-10000	0	16
DLX1	0.041	0.008	-10000	0	0	19	19
TCF3	0.037	0.014	-10000	0	0	71	71
FOS	0.025	0.029	-10000	0	-0.051	28	28
SMAD3/SMAD4/Max	0.063	0.068	-10000	0	-0.13	11	11
Cbp/p300/SNIP1	0.058	0.057	-10000	0	-0.14	27	27
ZBTB17	0.039	0.012	0.1	4	-0.042	4	8
LAMC1	0.009	0.073	-10000	0	-0.26	25	25
TGIF2/HDAC complex/SMAD3/SMAD4	0.062	0.075	-10000	0	-0.14	24	24
IRF7	0.041	0.012	0.087	1	-10000	0	1
ESR1	0.046	0.036	0.12	91	0	92	183
HNF4A	0.038	0.012	-10000	0	0	47	47
MEF2C	-0.003	0.061	0.22	13	-0.23	16	29
SMAD2-3/SMAD4	0.071	0.074	-10000	0	-0.13	14	14
Cbp/p300/Src-1	0.058	0.062	-10000	0	-0.14	36	36
IGHV3OR16-13	0.009	0.061	-10000	0	-0.43	10	10
TGIF2/HDAC complex	0.038	0.012	-10000	0	0	54	54
CREBBP	0.038	0.014	-10000	0	-0.002	56	56
SKIL	0.025	0.021	-10000	0	0	228	228
HDAC1	0.038	0.013	-10000	0	0	56	56
HDAC2	0.038	0.012	-10000	0	0	47	47
SNIP1	0.039	0.011	-10000	0	0	38	38
GCN5L2	0.039	0.013	-10000	0	-0.045	3	3
SMAD3/SMAD4/TFE3	0.078	0.083	-10000	0	-0.16	27	27
MSG1/HSC70	0.053	0.027	-10000	0	-0.14	5	5
SMAD2	0.039	0.025	-10000	0	-0.064	20	20
SMAD3	0.035	0.046	-10000	0	-0.092	22	22
SMAD3/E2F4-5/DP1/p107/SMAD4	0.02	0.066	0.18	1	-0.19	21	22
SMAD2/SMAD2/SMAD4	-0.01	0.061	0.17	7	-0.17	44	51
NCOR1	0.037	0.013	-10000	0	0	61	61
NCOA2	0.037	0.014	-10000	0	0	71	71
NCOA1	0.04	0.009	-10000	0	0	28	28
MYOD/E2A	0.052	0.024	-10000	0	-0.14	1	1
SMAD2-3/SMAD4/SP1/MIZ-1	0.082	0.12	-10000	0	-0.2	7	7
IFNB1	0.012	0.052	0.27	3	-0.15	3	6
SMAD3/SMAD4/MEF2C	0.052	0.084	0.28	2	-0.22	16	18
CITED1	0.039	0.01	-10000	0	0	35	35
SMAD2-3/SMAD4/ARC105	0.068	0.068	-10000	0	-0.12	13	13
RBL1	0.037	0.013	-10000	0	0	61	61
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.024	0.074	-10000	0	-0.4	7	7
RUNX1-3/PEBPB2	0.064	0.044	-10000	0	-0.11	14	14
SMAD7	-0.003	0.14	-10000	0	-0.38	30	30
MYC/MIZ-1	0.017	0.059	0.2	4	-0.14	52	56
SMAD3/SMAD4	-0.006	0.1	0.26	1	-0.33	30	31
IL10	0.022	0.061	0.22	18	-0.15	1	19
PIASy/HDAC complex	0.037	0.014	-10000	0	-0.037	5	5
PIAS3	0.04	0.01	-10000	0	-0.004	26	26
CDK2	0.038	0.015	-10000	0	-0.002	62	62
IL5	0.022	0.06	0.23	14	-10000	0	14
CDK4	0.038	0.015	-10000	0	-0.002	63	63
PIAS4	0.037	0.015	-10000	0	-0.037	5	5
ATF3	0.037	0.014	-10000	0	0	69	69
SMAD3/SMAD4/SP1	0.054	0.11	-10000	0	-0.17	36	36
FOXG1	-0.001	0.001	-10000	0	-10000	0	0
FOXO3	0.01	0.012	-10000	0	-0.11	5	5
FOXO1	0.01	0.012	-10000	0	-0.11	5	5
FOXO4	0.01	0.012	-10000	0	-0.11	5	5
heart looping	-0.003	0.061	0.22	13	-0.22	16	29
CEBPB	0.036	0.018	-10000	0	-0.061	5	5
SMAD3/SMAD4/DLX1	0.068	0.067	-10000	0	-0.13	10	10
MYOD1	0.04	0.008	-10000	0	0	20	20
SMAD3/SMAD4/HNF4	0.065	0.068	-10000	0	-0.12	14	14
SMAD3/SMAD4/GATA3	0.078	0.071	-10000	0	-0.13	6	6
SnoN/SIN3/HDAC complex/NCoR1	0.025	0.021	-10000	0	0	228	228
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.085	0.085	-10000	0	-0.14	4	4
SMAD3/SMAD4/SP1-3	0.07	0.12	-10000	0	-0.2	33	33
MED15	0	0	-10000	0	-10000	0	0
SP1	0.018	0.067	-10000	0	-0.1	121	121
SIN3B	0.037	0.013	-10000	0	0	65	65
SIN3A	0.04	0.009	-10000	0	0	28	28
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.1	0.073	-10000	0	-0.17	12	12
ITGB5	-0.006	0.094	0.21	13	-0.26	35	48
TGIF/SIN3/HDAC complex/CtBP	0.007	0.089	-10000	0	-0.26	33	33
SMAD3/SMAD4/AR	0.042	0.091	-10000	0	-0.14	60	60
AR	0.033	0.017	-10000	0	0	122	122
negative regulation of cell growth	0.018	0.074	0.19	1	-0.22	28	29
SMAD3/SMAD4/MYOD	0.068	0.068	-10000	0	-0.13	13	13
E2F5	0.037	0.014	-10000	0	0	71	71
E2F4	0.036	0.015	-10000	0	0	79	79
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.098	0.081	-10000	0	-0.14	11	11
SMAD2-3/SMAD4/FOXO1-3a-4	0.025	0.052	-10000	0	-0.29	7	7
TFDP1	0.038	0.012	-10000	0	0	52	52
SMAD3/SMAD4/AP1	0.033	0.11	0.26	3	-0.23	38	41
SMAD3/SMAD4/RUNX2	0.065	0.07	-10000	0	-0.13	17	17
TGIF2	0.038	0.012	-10000	0	0	54	54
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.04	0.01	-10000	0	0	31	31

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.016	0.009	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.064	0.063	0.18	81	-0.11	18	99
CDKN1B	0.017	0.092	0.21	39	-0.3	27	66
CDKN1A	0.009	0.084	0.21	14	-0.3	30	44
FRAP1	0.04	0.009	-10000	0	0	27	27
PRKDC	0.039	0.011	-10000	0	0	44	44
FOXO3	0.006	0.079	-10000	0	-0.29	33	33
AKT1	0.007	0.08	-10000	0	-0.31	30	30
BAD	0.041	0.005	-10000	0	0	9	9
AKT3	0.005	0.043	-10000	0	-0.2	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.079	-10000	0	-0.29	33	33
AKT1/ASK1	0.028	0.088	-10000	0	-0.28	35	35
BAD/YWHAZ	0.056	0.044	-10000	0	-0.12	7	7
RICTOR	0.037	0.014	-10000	0	0	68	68
RAF1	0.04	0.008	-10000	0	0	21	21
JNK cascade	-0.026	0.086	0.28	35	-10000	0	35
TSC1	0.003	0.078	0.23	2	-0.3	30	32
YWHAZ	0.034	0.016	-10000	0	0	102	102
AKT1/RAF1	0.035	0.093	-10000	0	-0.3	33	33
EP300	0.036	0.014	-10000	0	0	73	73
mol:GDP	0.006	0.081	-10000	0	-0.3	33	33
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.001	0.08	-10000	0	-0.3	34	34
YWHAQ	0.04	0.009	-10000	0	0	28	28
TBC1D4	0.007	0.028	0.24	5	-0.17	3	8
MAP3K5	0.037	0.014	-10000	0	0	69	69
MAPKAP1	0.04	0.009	-10000	0	0	27	27
negative regulation of cell cycle	-0.027	0.083	0.3	13	-0.21	3	16
YWHAH	0.037	0.013	-10000	0	0	60	60
AKT1S1	0.008	0.081	0.22	11	-0.3	27	38
CASP9	0.002	0.079	-10000	0	-0.3	31	31
YWHAB	0.038	0.012	-10000	0	0	52	52
p27Kip1/KPNA1	0.037	0.11	0.27	10	-0.3	32	42
GBL	0.04	0.009	-10000	0	0	25	25
PDK1/Src/Hsp90	0.05	0.021	-10000	0	-0.11	3	3
YWHAE	0.038	0.013	-10000	0	0	58	58
SRC	0.039	0.01	-10000	0	0	36	36
AKT2/p21CIP1	0.012	0.075	0.21	14	-0.26	27	41
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.091	-10000	0	-0.35	26	26
CHUK	0.001	0.08	-10000	0	-0.31	31	31
BAD/BCL-XL	0.028	0.086	-10000	0	-0.3	28	28
mTORC2	0.078	0.062	-10000	0	-0.12	33	33
AKT2	0.016	0.017	-10000	0	-0.2	3	3
FOXO1-3a-4/14-3-3 family	0.028	0.1	0.24	2	-0.37	13	15
PDPK1	0.04	0.009	-10000	0	0	25	25
MDM2	0.006	0.087	0.2	13	-0.3	33	46
MAPKKK cascade	-0.034	0.092	0.3	33	-10000	0	33
MDM2/Cbp/p300	0.039	0.1	0.32	3	-0.3	33	36
TSC1/TSC2	-0.003	0.082	0.29	4	-0.29	33	37
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.1	0.31	3	-0.29	33	36
glucose import	-0.003	0.034	0.21	11	-0.16	3	14
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.023	0.087	0.28	1	-0.28	16	17
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.003	0.032	0.21	10	-0.16	3	13
GSK3A	0.005	0.078	0.22	3	-0.3	29	32
FOXO1	0.006	0.079	-10000	0	-0.29	33	33
GSK3B	0.007	0.088	0.21	16	-0.3	33	49
SFN	0.036	0.015	-10000	0	0	86	86
G1/S transition of mitotic cell cycle	0.007	0.094	0.3	10	-0.3	32	42
p27Kip1/14-3-3 family	0.023	0.078	-10000	0	-0.3	13	13
PRKACA	0.035	0.015	-10000	0	0	89	89
KPNA1	0.039	0.01	-10000	0	0	33	33
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0.04	0.009	-10000	0	0	25	25
RHEB	0.037	0.013	-10000	0	0	64	64
CREBBP	0.038	0.012	-10000	0	0	54	54

×

Atypical NF-kappaB pathway

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
BCL3/RelA	0.055	0.027	-10000	0	-0.16	5	5
FBXW11	0.04	0.009	-10000	0	0	25	25
NF kappa B1 p50/c-Rel	0.027	0.038	-10000	0	-0.12	30	30
NF kappa B1 p50/RelA/I kappa B alpha	0.021	0.076	-10000	0	-0.21	23	23
NFKBIA	0.006	0.062	-10000	0	-0.15	51	51
MAPK14	0.04	0.009	-10000	0	0	28	28
NF kappa B1 p105/p50	0.026	0.04	-10000	0	-0.12	30	30
ARRB2	0.014	0.028	-10000	0	-0.2	9	9
REL	0.04	0.008	-10000	0	0	20	20
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.025	0.04	-10000	0	-0.12	31	31
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.04	-10000	0	-0.12	32	32
PIK3CA	0.03	0.019	-10000	0	0	155	155
NF kappa B1 p50 dimer	0.019	0.041	-10000	0	-0.14	31	31
PIK3R1	0.034	0.017	-10000	0	0	108	108
NFKB1	-0.016	0.009	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
positive regulation of anti-apoptosis	0.013	0.051	0.14	2	-0.14	35	37
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.024	0.082	-10000	0	-0.23	21	21
SRC	0.039	0.01	-10000	0	0	36	36
PI3K	0.024	0.061	-10000	0	-0.15	47	47
NF kappa B1 p50/RelA	0.013	0.052	0.14	2	-0.14	35	37
IKBKB	0.039	0.011	-10000	0	0	44	44
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.009	-10000	0	0	25	25
SYK	0.037	0.014	-10000	0	0	70	70
I kappa B alpha/PIK3R1	0.018	0.068	0.19	1	-0.15	49	50
cell death	0.02	0.077	-10000	0	-0.22	22	22
NF kappa B1 p105/c-Rel	0.027	0.038	-10000	0	-0.12	30	30
LCK	0.04	0.009	-10000	0	0	29	29
BCL3	0.039	0.011	-10000	0	0	40	40

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.037	0.013	-10000	0	0	64	64
mol:S1P	0.001	0.007	-10000	0	-0.028	24	24
S1P1/S1P/Gi	0.007	0.081	-10000	0	-0.18	59	59
GNAO1	0.033	0.024	-10000	0	-0.05	20	20
S1P/S1P3/G12/G13	0.047	0.032	-10000	0	-0.066	25	25
AKT1	0.015	0.1	-10000	0	-0.45	21	21
AKT3	-0.02	0.23	-10000	0	-0.97	27	27
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.037	0.013	-10000	0	0	64	64
GNAI2	0.04	0.02	-10000	0	-0.049	22	22
GNAI3	0.038	0.021	-10000	0	-0.047	20	20
GNAI1	0.034	0.022	-10000	0	-0.046	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.007	-10000	0	-0.03	24	24
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.041	0.006	-10000	0	0	12	12
mol:Ca2+	-0.001	0.1	0.16	1	-0.27	49	50
MAPK3	-0.009	0.096	0.21	1	-0.26	50	51
MAPK1	-0.004	0.089	-10000	0	-0.27	38	38
JAK2	-0.018	0.11	0.18	6	-0.3	52	58
CXCR4	-0.01	0.099	0.19	3	-0.27	49	52
FLT1	0.04	0.023	-10000	0	-0.059	20	20
RhoA/GDP	0.03	0.012	-10000	0	-0.13	3	3
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
SRC	-0.002	0.099	0.22	15	-0.27	42	57
S1P/S1P3/Gi	0	0.1	0.16	1	-0.27	48	49
RAC1	0.039	0.01	-10000	0	0	34	34
RhoA/GTP	0.01	0.11	-10000	0	-0.26	47	47
VEGFA	0.003	0.011	0.018	97	-0.038	23	120
S1P/S1P2/Gi	-0.002	0.089	0.14	1	-0.24	42	43
VEGFR1 homodimer/VEGFA homodimer	0.036	0.032	-10000	0	-0.088	25	25
RHOA	0.041	0.007	-10000	0	0	14	14
S1P/S1P3/Gq	0.018	0.037	-10000	0	-0.14	25	25
GNAQ	0.038	0.012	-10000	0	0	49	49
GNAZ	0.038	0.021	-10000	0	-0.047	21	21
G12/G13	0.054	0.03	-10000	0	-0.14	9	9
GNA14	0.039	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GNA12	0.04	0.01	-10000	0	0	32	32
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	61	61
Rac1/GTP	0.009	0.1	-10000	0	-0.26	47	47

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.039	0.01	0	34	-9999	0	34
PI3K Class IB/PDE3B	0.039	0.01	-9999	0	0	34	34
PDE3B	0.039	0.01	-9999	0	0	34	34

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.038	0.012	-10000	0	0	49	49
SMAD2	0.008	0.054	0.19	8	-0.23	6	14
SMAD3	0.014	0.054	0.22	2	-0.3	4	6
SMAD3/SMAD4	-0.017	0.16	-10000	0	-0.39	79	79
SMAD4/Ubc9/PIASy	0.066	0.042	-10000	0	-0.13	11	11
SMAD2/SMAD2/SMAD4	0.046	0.086	0.28	1	-0.21	5	6
PPM1A	0.041	0.007	-10000	0	0	16	16
CALM1	0.04	0.01	-10000	0	0	31	31
SMAD2/SMAD4	0.026	0.054	0.22	3	-0.19	8	11
MAP3K1	0.036	0.014	-10000	0	0	77	77
TRAP-1/SMAD4	0.049	0.044	-10000	0	-0.14	24	24
MAPK3	0.041	0.007	-10000	0	0	17	17
MAPK1	0.039	0.012	-10000	0	0	46	46
NUP214	0.039	0.01	-10000	0	0	33	33
CTDSP1	0.041	0.006	-10000	0	0	13	13
CTDSP2	0.039	0.011	-10000	0	0	42	42
CTDSPL	0.041	0.006	-10000	0	0	10	10
KPNB1	0.04	0.01	-10000	0	0	31	31
TGFBRAP1	0.04	0.008	-10000	0	0	20	20
UBE2I	0.04	0.009	-10000	0	0	27	27
NUP153	0.037	0.014	-10000	0	0	67	67
KPNA2	0.036	0.015	-10000	0	0	86	86
PIAS4	0.038	0.012	-10000	0	0	55	55

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.07	0.067	-10000	0	-0.11	45	45
MAP4K1	0.039	0.012	-10000	0	0	46	46
MAP3K8	0.04	0.008	-10000	0	0	21	21
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.041	0.007	-10000	0	0	17	17
CRKL	0.039	0.011	-10000	0	0	38	38
MAP3K1	0.004	0.062	-10000	0	-0.23	18	18
JUN	-0.007	0.11	0.24	1	-0.51	23	24
MAP3K7	0.005	0.064	0.21	5	-0.21	21	26
GRAP2	0.038	0.013	-10000	0	0	57	57
CRK	0.038	0.012	-10000	0	0	52	52
MAP2K4	-0.005	0.078	0.23	1	-0.28	24	25
LAT	0.041	0.006	-10000	0	0	13	13
LCP2	0.034	0.016	-10000	0	0	102	102
MAPK8	-0.003	0.12	-10000	0	-0.55	23	23
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.015	0.067	-10000	0	-0.21	20	20
LAT/GRAP2/SLP76/HPK1/HIP-55	0.079	0.077	-10000	0	-0.11	45	45

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.038	0.013	-10000	0	0	56	56
HDAC2	0.038	0.012	-10000	0	0	47	47
GNB1/GNG2	0.071	0.042	-10000	0	-0.12	18	18
forebrain development	0.014	0.11	-10000	0	-0.38	30	30
GNAO1	0.035	0.016	-10000	0	0	101	101
SMO/beta Arrestin2	0.054	0.026	-10000	0	-0.14	4	4
SMO	0.04	0.01	-10000	0	-0.001	33	33
ARRB2	0.039	0.011	-10000	0	0	44	44
GLI3/SPOP	0.02	0.13	-10000	0	-0.36	30	30
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.04	0.009	-10000	0	0	26	26
GNAI2	0.041	0.007	-10000	0	0	15	15
SIN3/HDAC complex	0.076	0.054	-10000	0	-0.12	10	10
GNAI1	0.035	0.016	-10000	0	0	95	95
XPO1	0.039	0.012	-10000	0	-0.002	42	42
GLI1/Su(fu)	0.02	0.11	-10000	0	-0.41	25	25
SAP30	0.038	0.012	-10000	0	0	55	55
mol:GDP	0.04	0.01	-10000	0	-0.001	33	33
MIM/GLI2A	0.032	0.026	-10000	0	-0.12	2	2
IFT88	0.037	0.014	-10000	0	0	70	70
GNAI3	0.039	0.011	-10000	0	0	45	45
GLI2	0.016	0.073	0.19	6	-0.24	15	21
GLI3	0.003	0.12	0.22	3	-0.36	30	33
CSNK1D	0.04	0.009	-10000	0	0	28	28
CSNK1E	0.038	0.013	-10000	0	0	57	57
SAP18	0.039	0.01	-10000	0	0	34	34
embryonic digit morphogenesis	0.037	0.014	-10000	0	0	70	70
GNG2	0.039	0.01	-10000	0	0	34	34
Gi family/GTP	0.002	0.076	-10000	0	-0.24	29	29
SIN3B	0.037	0.013	-10000	0	0	65	65
SIN3A	0.04	0.009	-10000	0	0	28	28
GLI3/Su(fu)	0.017	0.12	0.23	3	-0.32	36	39
GLI2/Su(fu)	0.024	0.083	0.19	5	-0.25	21	26
FOXA2	0.025	0.094	-10000	0	-0.58	11	11
neural tube patterning	0.014	0.11	-10000	0	-0.38	30	30
SPOP	0.04	0.009	-10000	0	0	27	27
Su(fu)/PIAS1	0.04	0.06	0.21	1	-0.18	27	28
GNB1	0.041	0.005	-10000	0	0	7	7
CSNK1G2	0.037	0.013	-10000	0	0	64	64
CSNK1G3	0.039	0.011	-10000	0	0	38	38
MTSS1	0.032	0.026	-10000	0	-0.12	2	2
embryonic limb morphogenesis	0.014	0.11	-10000	0	-0.38	30	30
SUFU	0.023	0.039	-10000	0	-0.24	10	10
LGALS3	0.037	0.014	-10000	0	0	70	70
catabolic process	0.026	0.13	-10000	0	-0.35	31	31
GLI3A/CBP	0.047	0.015	-10000	0	-10000	0	0
KIF3A	0.038	0.012	-10000	0	0	51	51
GLI1	0.013	0.11	-10000	0	-0.38	30	30
RAB23	0.041	0.007	-10000	0	0	15	15
CSNK1A1	0.04	0.009	-10000	0	0	26	26
IFT172	0.04	0.009	-10000	0	0	28	28
RBBP7	0.04	0.009	-10000	0	0	26	26
Su(fu)/Galectin3	0.037	0.058	0.21	1	-0.18	25	26
GNAZ	0.039	0.011	-10000	0	0	42	42
RBBP4	0.038	0.012	-10000	0	0	46	46
CSNK1G1	0.041	0.008	-10000	0	0	19	19
PIAS1	0.04	0.009	-10000	0	0	28	28
PRKACA	0.035	0.015	-10000	0	0	89	89
GLI2/SPOP	0.034	0.08	0.21	1	-0.24	17	18
STK36	0.04	0.011	-10000	0	-0.003	33	33
Gi family/GNB1/GNG2/GDP	0	0.086	-10000	0	-0.26	33	33
PTCH1	0.014	0.1	-10000	0	-0.35	30	30
MIM/GLI1	0.026	0.099	-10000	0	-0.35	21	21
CREBBP	0.047	0.015	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.004	0.11	0.18	7	-0.31	38	45

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.034	0.25	0.49	2	-0.56	56	58
PCK1	-0.092	0.4	-10000	0	-1.1	72	72
HNF4A	-0.067	0.34	0.57	5	-0.76	86	91
KCNJ11	-0.003	0.23	0.53	1	-0.54	30	31
AKT1	0.006	0.17	-10000	0	-0.35	26	26
response to starvation	-0.015	0.045	-10000	0	-0.12	79	79
DLK1	0.006	0.24	0.64	3	-0.55	27	30
NKX2-1	-0.002	0.15	0.36	3	-0.32	26	29
ACADM	-0.049	0.27	0.54	1	-0.6	66	67
TAT	-0.023	0.19	-10000	0	-0.52	22	22
CEBPB	0.039	0.017	-10000	0	-0.064	2	2
CEBPA	0.042	0.016	-10000	0	-0.066	1	1
TTR	0.042	0.17	0.52	2	-0.92	4	6
PKLR	-0.021	0.25	0.45	3	-0.56	42	45
APOA1	-0.12	0.47	-10000	0	-1.1	94	94
CPT1C	-0.026	0.24	0.49	1	-0.58	42	43
ALAS1	-0.005	0.18	-10000	0	-0.79	5	5
TFRC	-0.054	0.38	-10000	0	-0.94	69	69
FOXF1	0.035	0.015	-10000	0	-10000	0	0
NF1	0.039	0.02	-10000	0	-0.16	1	1
HNF1A (dimer)	0.009	0.001	-10000	0	-10000	0	0
CPT1A	-0.04	0.27	0.53	1	-0.59	61	62
HMGCS1	-0.032	0.26	0.47	6	-0.58	62	68
NR3C1	0.048	0.015	-10000	0	-10000	0	0
CPT1B	-0.033	0.24	-10000	0	-0.56	48	48
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.041	0.006	-10000	0	-10000	0	0
GCK	-0.029	0.24	0.48	3	-0.57	44	47
CREB1	0.021	0.095	-10000	0	-0.21	74	74
IGFBP1	-0.001	0.15	-10000	0	-0.52	3	3
PDX1	0.014	0.14	0.4	1	-0.29	25	26
UCP2	-0.055	0.3	0.49	8	-0.65	81	89
ALDOB	-0.003	0.23	-10000	0	-0.53	31	31
AFP	0.015	0.049	-10000	0	-10000	0	0
BDH1	-0.053	0.27	-10000	0	-0.59	72	72
HADH	-0.003	0.23	-10000	0	-0.48	51	51
F2	-0.029	0.31	-10000	0	-0.73	38	38
HNF1A	0.009	0.001	-10000	0	-10000	0	0
G6PC	0.028	0.088	-10000	0	-10000	0	0
SLC2A2	0.034	0.16	-10000	0	-0.42	2	2
INS	0.03	0.013	0.18	1	-10000	0	1
FOXA1	0.056	0.016	-10000	0	-10000	0	0
FOXA3	0.022	0.12	-10000	0	-0.2	110	110
FOXA2	0.016	0.29	-10000	0	-0.59	37	37
ABCC8	-0.003	0.23	0.53	1	-0.55	24	25
ALB	0.016	0.05	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.051	0.093	-10000	0	-0.21	34	34
Ran/GTP/Exportin 1/HDAC1	-0.03	0.032	-10000	0	-0.12	48	48
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.1	0.24	1	-0.29	30	31
SUMO1	0.041	0.006	-10000	0	0	13	13
ZFPM1	0.036	0.015	-10000	0	0	86	86
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.035	-10000	0	-0.15	25	25
FKBP3	0.039	0.01	-10000	0	0	34	34
Histones	0.069	0.087	0.24	1	-0.22	19	20
YY1/LSF	0.012	0.083	-10000	0	-0.22	45	45
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	13	13
I kappa B alpha/HDAC3	0.016	0.061	-10000	0	-0.18	39	39
I kappa B alpha/HDAC1	0.031	0.09	0.22	1	-0.23	48	49
SAP18	0.039	0.01	-10000	0	0	34	34
RELA	0.017	0.086	0.22	3	-0.37	13	16
HDAC1/Smad7	0.062	0.053	-10000	0	-0.12	33	33
RANGAP1	0.038	0.013	-10000	0	0	57	57
HDAC3/TR2	0.047	0.061	0.22	1	-0.2	19	20
NuRD/MBD3 Complex	0.01	0.098	0.17	5	-0.29	32	37
NF kappa B1 p50/RelA	0.023	0.1	0.25	1	-0.26	37	38
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.039	0.01	-10000	0	0	35	35
GATA1	0.042	0.002	-10000	0	0	1	1
Mad/Max	0.059	0.014	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.005	0.1	-10000	0	-0.27	38	38
RBBP7	0.04	0.009	-10000	0	0	26	26
NPC	0.02	0.022	-10000	0	-0.085	23	23
RBBP4	0.039	0.012	-10000	0	0	46	46
MAX	0.041	0.007	-10000	0	0	16	16
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.009	-10000	0	0	25	25
NFKBIA	0.009	0.071	-10000	0	-0.27	30	30
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.006	0.091	-10000	0	-0.28	30	30
SIN3 complex	0.076	0.054	-10000	0	-0.12	10	10
SMURF1	0.041	0.008	-10000	0	0	19	19
CHD3	0.038	0.012	-10000	0	0	55	55
SAP30	0.038	0.012	-10000	0	0	55	55
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.037	0.013	-10000	0	0	61	61
YY1/HDAC3	0.016	0.078	-10000	0	-0.24	30	30
YY1/HDAC2	0.015	0.077	-10000	0	-0.21	41	41
YY1/HDAC1	0.012	0.079	-10000	0	-0.22	41	41
NuRD/MBD2 Complex (MeCP1)	0.011	0.097	0.17	5	-0.29	29	34
PPARG	0.031	0.067	0.2	6	-0.2	24	30
HDAC8/hEST1B	0.042	0.036	-10000	0	-0.11	20	20
UBE2I	0.04	0.009	-10000	0	0	27	27
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.009	-10000	0	0	25	25
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
HDAC3/SMRT (N-CoR2)	0.048	0.06	0.22	1	-0.19	20	21
MBD3L2	0.039	0.011	-10000	0	0	40	40
ubiquitin-dependent protein catabolic process	0.061	0.053	-10000	0	-0.12	33	33
CREBBP	0.038	0.012	-10000	0	0	54	54
NuRD/MBD3/MBD3L2 Complex	0.008	0.1	0.19	8	-0.27	42	50
HDAC1	0.038	0.013	-10000	0	0	56	56
HDAC3	0.022	0.038	-10000	0	-0.29	5	5
HDAC2	0.038	0.012	-10000	0	0	47	47
YY1	0.005	0.057	-10000	0	-0.24	25	25
HDAC8	0.04	0.009	-10000	0	0	26	26
SMAD7	0.039	0.011	-10000	0	0	45	45
NCOR2	0.04	0.009	-10000	0	0	28	28
MXD1	0.041	0.007	-10000	0	0	18	18
STAT3	0.009	0.066	-10000	0	-0.24	33	33
NFKB1	0.036	0.015	-10000	0	0	84	84
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.04	0.009	-10000	0	0	30	30
YY1/LSF/HDAC1	0.022	0.092	-10000	0	-0.21	48	48
YY1/SAP30/HDAC1	0.025	0.085	-10000	0	-0.2	42	42
EP300	0.036	0.014	-10000	0	0	73	73
STAT3 (dimer non-phopshorylated)	0.009	0.066	-10000	0	-0.24	33	33
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.071	-10000	0	-0.27	30	30
histone deacetylation	0.011	0.096	0.17	5	-0.29	29	34
STAT3 (dimer non-phopshorylated)/HDAC3	0.021	0.084	-10000	0	-0.28	22	22
nuclear export	-0.041	0.036	0.11	20	-10000	0	20
PRKACA	0.035	0.015	-10000	0	0	89	89
GATAD2B	0.038	0.012	-10000	0	0	52	52
GATAD2A	0.038	0.013	-10000	0	0	59	59
GATA2/HDAC3	0.048	0.059	0.22	1	-0.19	20	21
GATA1/HDAC1	0.049	0.044	-10000	0	-0.14	27	27
GATA1/HDAC3	0.051	0.06	0.22	1	-0.2	20	21
CHD4	0.036	0.015	-10000	0	0	79	79
TNF-alpha/TNFR1A	0.047	0.038	-10000	0	-0.14	15	15
SIN3/HDAC complex/Mad/Max	0.01	0.092	-10000	0	-0.3	26	26
NuRD Complex	0.004	0.1	0.19	8	-0.28	39	47
positive regulation of chromatin silencing	0.065	0.085	0.23	1	-0.21	19	20
SIN3B	0.037	0.013	-10000	0	0	65	65
MTA2	0.041	0.005	-10000	0	0	9	9
SIN3A	0.04	0.009	-10000	0	0	28	28
XPO1	0.039	0.011	-10000	0	0	39	39
SUMO1/HDAC1	0.037	0.065	-10000	0	-0.18	25	25
HDAC complex	0.072	0.078	-10000	0	-0.14	55	55
GATA1/Fog1	0.053	0.022	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.057	0.062	-10000	0	-0.13	44	44
TNF	0.04	0.009	-10000	0	0	26	26
negative regulation of cell growth	0.01	0.091	-10000	0	-0.29	26	26
NuRD/MBD2/PRMT5 Complex	0.011	0.097	0.17	5	-0.29	29	34
Ran/GTP/Exportin 1	0.038	0.071	0.18	1	-0.2	26	27
NF kappa B/RelA/I kappa B alpha	0.016	0.083	-10000	0	-0.28	27	27
SIN3/HDAC complex/NCoR1	-0.001	0.096	0.17	1	-0.25	45	46
TFCP2	0.039	0.01	-10000	0	0	37	37
NR2C1	0.039	0.011	-10000	0	0	41	41
MBD3	0.037	0.014	-10000	0	0	67	67
MBD2	0.039	0.011	-10000	0	0	42	42

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.034	0.016	-10000	0	0	101	101
CDC42/GTP	0.007	0.085	-10000	0	-0.23	36	36
PLCG1	-0.013	0.072	-10000	0	-0.18	69	69
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.041	0.007	-10000	0	0	15	15
GNAI3	0.039	0.011	-10000	0	0	45	45
G12/G13	0.054	0.03	-10000	0	-0.14	9	9
cell migration	0.007	0.084	-10000	0	-0.22	36	36
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.013	0.073	-10000	0	-0.18	68	68
MAPK1	-0.006	0.063	-10000	0	-0.16	58	58
S1P/S1P5/Gi	-0.005	0.079	-10000	0	-0.18	70	70
GNAI1	0.035	0.016	-10000	0	0	95	95
CDC42/GDP	0.029	0.014	-10000	0	-0.13	4	4
S1P/S1P5/G12	0.027	0.007	-10000	0	-10000	0	0
RHOA	-0.012	0.038	0.18	17	-0.17	1	18
S1P/S1P4/Gi	-0.005	0.079	-10000	0	-0.18	70	70
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.039	0.011	-10000	0	0	42	42
S1P/S1P4/G12/G13	0.047	0.024	-10000	0	-0.099	9	9
GNA12	0.04	0.01	-10000	0	0	32	32
GNA13	0.04	0.009	-10000	0	0	28	28
CDC42	0.04	0.009	-10000	0	0	24	24

×

Ephrin A reverse signaling

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
MAPKKK cascade	0.037	0.041	-10000	0	-0.11	31	31
EFNA5	0.034	0.016	-10000	0	0	103	103
FYN	-0.013	0.036	0.18	7	-10000	0	7
neuron projection morphogenesis	0.037	0.041	-10000	0	-0.11	31	31
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.038	0.042	-10000	0	-0.11	31	31
EPHA5	0.04	0.009	-10000	0	0	26	26

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.007	0.085	0.22	36	-10000	0	36
GNAI2	0.041	0.007	-10000	0	0	15	15
S1P/S1P5/G12	0.027	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.034	0.016	-10000	0	0	101	101
RhoA/GTP	0.007	0.086	-10000	0	-0.23	36	36
negative regulation of cAMP metabolic process	-0.005	0.078	-10000	0	-0.18	70	70
GNAZ	0.039	0.011	-10000	0	0	42	42
GNAI3	0.039	0.011	-10000	0	0	45	45
GNA12	0.04	0.01	-10000	0	0	32	32
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.005	0.079	-10000	0	-0.18	70	70
RhoA/GDP	0.03	0.012	-10000	0	-0.13	3	3
RHOA	0.041	0.007	-10000	0	0	14	14
GNAI1	0.035	0.016	-10000	0	0	95	95

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.038	0.012	-10000	0	0	51	51
NFATC1	0.019	0.1	0.25	3	-0.33	17	20
NFATC2	0.027	0.058	0.17	9	-0.22	10	19
NFATC3	0.026	0.016	-10000	0	-10000	0	0
YWHAE	0.038	0.013	-10000	0	0	58	58
Calcineurin A alpha-beta B1/CABIN1	-0.003	0.086	0.18	1	-0.26	27	28
Exportin 1/Ran/NUP214	0.067	0.052	-10000	0	-0.12	33	33
mol:DAG	0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.028	0.097	-10000	0	-0.24	21	21
BCL2/BAX	0.051	0.026	-10000	0	-0.14	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.029	0.019	-10000	0	-0.13	5	5
CaM/Ca2+	0.029	0.019	-10000	0	-0.13	5	5
BAX	0.04	0.008	-10000	0	0	22	22
MAPK14	0.04	0.009	-10000	0	0	28	28
BAD	0.041	0.005	-10000	0	0	9	9
CABIN1/MEF2D	0.013	0.09	-10000	0	-0.25	25	25
Calcineurin A alpha-beta B1/BCL2	0.036	0.014	-10000	0	0	76	76
FKBP8	0.036	0.014	-10000	0	0	74	74
activation-induced cell death of T cells	-0.013	0.089	0.25	25	-10000	0	25
KPNB1	0.04	0.01	-10000	0	0	31	31
KPNA2	0.036	0.015	-10000	0	0	86	86
XPO1	0.039	0.011	-10000	0	0	39	39
SFN	0.036	0.015	-10000	0	0	86	86
MAP3K8	0.041	0.008	-10000	0	0	21	21
NFAT4/CK1 alpha	0.028	0.045	0.19	2	-0.16	9	11
MEF2D/NFAT1/Cbp/p300	0.071	0.091	0.25	1	-0.22	8	9
CABIN1	-0.003	0.086	0.18	1	-0.27	27	28
CALM1	0.04	0.01	-10000	0	0	31	31
RAN	0.041	0.006	-10000	0	0	13	13
MAP3K1	0.036	0.014	-10000	0	0	77	77
CAMK4	0.037	0.013	-10000	0	0	64	64
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.041	0.007	-10000	0	0	17	17
YWHAH	0.037	0.013	-10000	0	0	60	60
Calcineurin A alpha-beta B1/AKAP79/PKA	0.051	0.027	-10000	0	-0.14	2	2
YWHAB	0.038	0.012	-10000	0	0	52	52
MAPK8	0.04	0.01	-10000	0	0	30	30
MAPK9	0.039	0.011	-10000	0	0	39	39
YWHAG	0.04	0.009	-10000	0	0	25	25
FKBP1A	0.038	0.012	-10000	0	0	50	50
NFAT1-c-4/YWHAQ	0.035	0.11	0.27	2	-0.31	17	19
PRKCH	0.039	0.011	-10000	0	0	41	41
CABIN1/Cbp/p300	0.044	0.052	-10000	0	-0.16	26	26
CASP3	0.037	0.014	-10000	0	0	67	67
PIM1	0.039	0.011	-10000	0	0	45	45
Calcineurin A alpha-beta B1/FKBP12/FK506	0.026	0.012	-10000	0	-0.1	2	2
apoptosis	0.019	0.037	-10000	0	-0.2	11	11
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.076	-10000	0	-0.27	17	17
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.039	0.01	-10000	0	0	36	36
JNK2/NFAT4	0.026	0.068	-10000	0	-0.14	68	68
BAD/BCL-XL	0.053	0.032	-10000	0	-0.14	11	11
PRKCD	0.038	0.013	-10000	0	0	56	56
NUP214	0.04	0.01	-10000	0	0	33	33
PRKCZ	0.043	0.002	-10000	0	-10000	0	0
PRKCA	0.035	0.015	-10000	0	0	90	90
PRKCG	0.041	0.005	-10000	0	0	7	7
PRKCQ	0.035	0.016	-10000	0	0	92	92
FKBP38/BCL2	0.046	0.03	-10000	0	-0.14	3	3
EP300	0.037	0.015	-10000	0	0	73	73
PRKCB1	0.038	0.012	-10000	0	0	48	48
CSNK2A1	0.038	0.012	-10000	0	0	54	54
NFATc/JNK1	0.032	0.11	0.26	2	-0.32	17	19
CaM/Ca2+/FKBP38	0.047	0.027	-10000	0	-0.13	4	4
FKBP12/FK506	0.028	0.013	-10000	0	-0.13	2	2
CSNK1A1	0.017	0.017	0.093	6	-0.11	3	9
CaM/Ca2+/CAMK IV	0.048	0.028	-10000	0	-0.11	7	7
NFATc/ERK1	0.035	0.11	0.26	3	-0.32	15	18
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.025	0.099	-10000	0	-0.24	24	24
NR4A1	0.017	0.075	0.19	22	-0.23	19	41
GSK3B	0.041	0.009	-10000	0	0	26	26
positive T cell selection	0.026	0.016	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.023	0.047	0.12	7	-0.18	11	18
RCH1/ KPNB1	0.035	0.064	-10000	0	-0.14	60	60
YWHAQ	0.04	0.009	-10000	0	0	28	28
PRKACA	0.036	0.016	-10000	0	0	89	89
AKAP5	0.041	0.008	-10000	0	0	19	19
MEF2D	0.041	0.01	-10000	0	0	28	28
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.034	0.016	-10000	0	0	102	102
NFATc/p38 alpha	0.034	0.11	0.26	3	-0.31	17	20
CREBBP	0.039	0.013	-10000	0	0	54	54
BCL2	0.036	0.014	-10000	0	0	76	76

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.037	0.015	-9999	-10000	0	0
SVIL	0.037	0.015	-9999	-10000	0	0
ZNF318	0.037	0.01	-9999	-0.035	2	2
JMJD2C	0.043	0.015	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.037	0.062	-9999	-0.1	77	77
CARM1	0.037	0.014	-9999	0	69	69
PRDX1	0.039	0.01	-9999	0	36	36
PELP1	0.039	0.01	-9999	0	36	36
CTNNB1	0.04	0.01	-9999	-10000	0	0
AKT1	0.039	0.01	-9999	0	37	37
PTK2B	0.034	0.017	-9999	-10000	0	0
MED1	-0.001	0	-9999	-10000	0	0
MAK	0.033	0.015	-9999	-0.034	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.041	0.01	-9999	-10000	0	0
GSN	0.04	0.012	-9999	-10000	0	0
NCOA2	0.037	0.014	-9999	0	71	71
NCOA6	0.04	0.012	-9999	-10000	0	0
DNA-PK	0.052	0.066	-9999	-0.14	46	46
NCOA4	0.04	0.008	-9999	0	23	23
PIAS3	0.041	0.009	-9999	-10000	0	0
cell proliferation	0.018	0.048	-9999	-0.42	6	6
XRCC5	0.039	0.011	-9999	0	39	39
UBE3A	0.043	0.005	-9999	-10000	0	0
T-DHT/AR/SNURF	0.038	0.063	-9999	-0.11	79	79
FHL2	0.025	0.069	-9999	-0.61	5	5
RANBP9	0.039	0.013	-9999	-10000	0	0
JMJD1A	0.052	0.019	-9999	-0.14	1	1
CDK6	0.032	0.018	-9999	0	129	129
TGFB1I1	0.042	0.006	-9999	-10000	0	0
T-DHT/AR/CyclinD1	0.013	0.079	-9999	-0.12	129	129
XRCC6	0.036	0.014	-9999	0	70	70
T-DHT/AR	0.036	0.057	-9999	-0.1	71	71
CTDSP1	0.041	0.006	-9999	0	13	13
CTDSP2	0.037	0.011	-9999	-10000	0	0
BRCA1	0.035	0.017	-9999	-10000	0	0
TCF4	0.036	0.013	-9999	0	59	59
CDKN2A	0.028	0.019	-9999	0	175	175
SRF	0.043	0.021	-9999	-0.14	4	4
NKX3-1	0.014	0.082	-9999	-0.3	30	30
KLK3	0.004	0.048	-9999	-10000	0	0
TMF1	0.039	0.011	-9999	0	38	38
HNRNPA1	-0.001	0	-9999	-10000	0	0
AOF2	0.041	0.009	-9999	-10000	0	0
APPL1	-0.011	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.033	0.065	-9999	-0.11	89	89
AR	0.037	0.02	-9999	-0.043	1	1
UBA3	0	0	-9999	-10000	0	0
PATZ1	-0.001	0	-9999	-10000	0	0
PAWR	0.041	0.007	-9999	0	18	18
PRKDC	0.038	0.011	-9999	0	44	44
PA2G4	0.039	0.008	-9999	0	25	25
UBE2I	0.04	0.009	-9999	0	27	27
T-DHT/AR/Cyclin D3/CDK11 p58	0.034	0.058	-9999	-0.095	81	81
RPS6KA3	0.038	0.014	-9999	-10000	0	0
T-DHT/AR/ARA70	0.035	0.066	-9999	-0.11	90	90
LATS2	0.039	0.009	-9999	0	28	28
T-DHT/AR/PRX1	0.031	0.06	-9999	-0.095	90	90
Cyclin D3/CDK11 p58	0.028	0.016	-9999	-0.13	5	5
VAV3	0.034	0.017	-9999	-10000	0	0
KLK2	0.021	0.065	-9999	-0.3	17	17
CASP8	0.04	0.009	-9999	0	28	28
T-DHT/AR/TIF2/CARM1	0.045	0.071	-9999	-0.11	72	72
TMPRSS2	0.013	0.09	-9999	-0.31	33	33
CCND1	0.031	0.018	-9999	0	144	144
PIAS1	0.041	0.01	-9999	-10000	0	0
mol:T-DHT	0.005	0.005	-9999	-0.032	3	3
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.04	0.013	-9999	-10000	0	0
T-DHT/AR/CDK6	0.017	0.076	-9999	-0.12	119	119
CMTM2	0.036	0.014	-9999	0	75	75
SNURF	0.041	0.006	-9999	0	10	10
ZMIZ1	0.005	0.005	-9999	-0.032	3	3
CCND3	0.039	0.01	-9999	0	33	33
TGIF1	-0.001	0	-9999	-10000	0	0
FKBP4	0.037	0.016	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.056	0.05	-10000	0	-0.11	21	21
fibroblast growth factor receptor signaling pathway	0.055	0.049	-10000	0	-0.11	21	21
LAMA1	0.034	0.017	-10000	0	0	108	108
PRNP	0.036	0.014	-10000	0	0	77	77
GPC1/SLIT2	0.018	0.072	-10000	0	-0.14	91	91
SMAD2	-0.021	0.035	0.2	7	-0.19	1	8
GPC1/PrPc/Cu2+	0.039	0.043	-10000	0	-0.11	35	35
GPC1/Laminin alpha1	0.046	0.032	-10000	0	-0.14	6	6
TDGF1	0.041	0.006	-10000	0	0	12	12
CRIPTO/GPC1	0.058	0.017	-10000	0	-0.14	1	1
APP/GPC1	0.047	0.046	-10000	0	-0.14	29	29
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.018	0.025	0.19	5	-0.12	1	6
FLT1	0.04	0.01	-10000	0	0	31	31
GPC1/TGFB/TGFBR1/TGFBR2	0.069	0.043	-10000	0	-0.12	17	17
SERPINC1	0.04	0.008	-10000	0	0	23	23
FYN	-0.016	0.026	0.19	5	-0.12	1	6
FGR	-0.019	0.025	0.1	18	-0.12	1	19
positive regulation of MAPKKK cascade	0.005	0.072	0.21	15	-0.2	15	30
SLIT2	0.028	0.02	-10000	0	0	184	184
GPC1/NRG	0.049	0.026	-10000	0	-0.14	1	1
NRG1	0.035	0.016	-10000	0	0	93	93
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.05	0.023	-10000	0	-0.11	6	6
LYN	-0.017	0.025	0.19	5	-0.12	1	6
mol:Spermine	-0.01	0.002	-10000	0	-10000	0	0
cell growth	0.055	0.049	-10000	0	-0.11	21	21
BMP signaling pathway	-0.04	0.009	0	26	-10000	0	26
SRC	-0.019	0.025	0.1	17	-0.12	1	18
TGFBR1	0.04	0.009	-10000	0	0	25	25
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.037	0.014	-10000	0	0	69	69
GPC1	0.04	0.009	-10000	0	0	26	26
TGFBR1 (dimer)	0.04	0.009	-10000	0	0	25	25
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.016	0.024	0.19	4	-0.12	1	5
HCK	-0.017	0.025	0.1	17	-10000	0	17
FGF2	0.039	0.011	-10000	0	0	45	45
FGFR1	0.033	0.017	-10000	0	0	122	122
VEGFR1 homodimer	0.04	0.01	-10000	0	0	31	31
TGFBR2	0.039	0.01	-10000	0	0	37	37
cell death	0.046	0.046	-10000	0	-0.14	29	29
ATIII/GPC1	0.057	0.019	-10000	0	-0.14	1	1
PLA2G2A/GPC1	0.051	0.026	-10000	0	-0.14	3	3
LCK	-0.019	0.025	0.19	5	-10000	0	5
neuron differentiation	0.049	0.026	-10000	0	-0.14	1	1
PrPc/Cu2+	0.019	0.038	-10000	0	-0.13	34	34
APP	0.038	0.012	-10000	0	0	51	51
TGFBR2 (dimer)	0.039	0.01	-10000	0	0	37	37

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.04	0.009	-10000	0	0	25	25
SPHK1	0.04	0.008	-10000	0	0	20	20
GNAI2	0.041	0.007	-10000	0	0	15	15
mol:S1P	0.015	0.029	-10000	0	-0.17	12	12
GNAO1	0.034	0.016	-10000	0	0	101	101
mol:Sphinganine-1-P	-0.019	0.006	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.051	0.048	0.19	1	-0.15	13	14
GNAI3	0.039	0.011	-10000	0	0	45	45
G12/G13	0.054	0.03	-10000	0	-0.14	9	9
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.041	0.006	-10000	0	0	12	12
S1P1/S1P	0.037	0.042	0.19	1	-0.15	12	13
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.035	0.016	-10000	0	0	95	95
S1P/S1P5/G12	0.032	0.038	-10000	0	-0.14	12	12
S1P/S1P3/Gq	0.015	0.079	-10000	0	-0.26	36	36
S1P/S1P4/Gi	-0.009	0.09	-10000	0	-0.2	71	71
GNAQ	0.038	0.012	-10000	0	0	49	49
GNAZ	0.039	0.011	-10000	0	0	42	42
GNA14	0.039	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GNA12	0.04	0.01	-10000	0	0	32	32
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	61	61
ABCC1	0.04	0.009	-10000	0	0	26	26

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.017	0.085	-10000	0	-0.38	21	21
Crk/p130 Cas/Paxillin	0.005	0.039	-10000	0	-0.18	5	5
JUN	0.003	0.062	0.19	4	-0.23	11	15
HRAS	0.04	0.01	-10000	0	0	31	31
RET51/GFRalpha1/GDNF/GRB10	0.09	0.04	-10000	0	-0.11	5	5
RAP1A	0.039	0.01	-10000	0	0	35	35
FRS2	0.039	0.011	-10000	0	0	40	40
RAP1A/GDP	0.024	0.03	-10000	0	-0.13	21	21
RET51/GFRalpha1/GDNF/DOK1	0.09	0.04	-10000	0	-0.11	5	5
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.04	0.009	-10000	0	0	27	27
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	52	52
RET9/GFRalpha1/GDNF/Enigma	0.063	0.035	-10000	0	-0.11	2	2
RHOA	0.041	0.007	-10000	0	0	14	14
RAP1A/GTP	0.075	0.051	-10000	0	-0.1	15	15
GRB7	0.037	0.013	-10000	0	0	63	63
RET51/GFRalpha1/GDNF	0.078	0.047	-10000	0	-0.11	3	3
MAPKKK cascade	0.048	0.046	-10000	0	-0.15	4	4
BCAR1	0.036	0.014	-10000	0	0	76	76
RET9/GFRalpha1/GDNF/IRS1	0.063	0.036	-10000	0	-0.11	5	5
lamellipodium assembly	0.03	0.051	0.14	2	-0.18	4	6
RET51/GFRalpha1/GDNF/SHC	0.089	0.039	-10000	0	-0.11	2	2
PIK3CA	0.03	0.019	-10000	0	0	155	155
RET9/GFRalpha1/GDNF/SHC	0.063	0.035	-10000	0	-0.11	2	2
RET9/GFRalpha1/GDNF/Shank3	0.066	0.031	-10000	0	-0.11	1	1
MAPK3	-0.008	0.066	0.18	43	-10000	0	43
DOK1	0.04	0.009	-10000	0	0	24	24
DOK6	0.037	0.013	-10000	0	0	61	61
PXN	0.041	0.007	-10000	0	0	14	14
neurite development	0.001	0.06	0.22	11	-0.2	5	16
DOK5	0.022	0.021	-10000	0	0	269	269
GFRA1	0.037	0.013	-10000	0	0	62	62
MAPK8	0.012	0.06	-10000	0	-0.24	8	8
HRAS/GTP	0.081	0.048	-10000	0	-0.15	4	4
tube development	0.064	0.03	0.24	5	-0.1	2	7
MAPK1	-0.009	0.062	0.18	40	-10000	0	40
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.021	0.046	-10000	0	-0.16	28	28
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
SRC	0.039	0.01	-10000	0	0	36	36
PDLIM7	0.039	0.01	-10000	0	0	36	36
RET51/GFRalpha1/GDNF/Dok6	0.092	0.055	-10000	0	-0.11	1	1
SHC1	0.04	0.01	-10000	0	0	31	31
RET51/GFRalpha1/GDNF/Dok4	0.086	0.041	-10000	0	-0.11	1	1
RET51/GFRalpha1/GDNF/Dok5	0.041	0.079	-10000	0	-0.11	85	85
PRKCA	0.035	0.015	-10000	0	0	90	90
HRAS/GDP	0.029	0.01	-10000	0	-0.13	1	1
CREB1	0.036	0.063	-10000	0	-0.21	20	20
PIK3R1	0.034	0.017	-10000	0	0	108	108
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.024	0.035	-10000	0	-0.14	12	12
RET51/GFRalpha1/GDNF/Grb7	0.085	0.043	-10000	0	-0.11	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.041	0.007	-10000	0	0	17	17
DOK4	0.038	0.012	-10000	0	0	52	52
JNK cascade	0.003	0.061	0.19	4	-0.23	11	15
RET9/GFRalpha1/GDNF/FRS2	0.06	0.041	-10000	0	-0.11	12	12
SHANK3	0.042	0.002	-10000	0	0	1	1
RASA1	0.037	0.014	-10000	0	0	71	71
NCK1	0.036	0.015	-10000	0	0	80	80
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.023	0.038	-10000	0	-0.14	25	25
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.027	0.049	-10000	0	-0.16	27	27
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.016	0.058	-10000	0	-0.16	34	34
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.028	0.043	-10000	0	-0.15	22	22
PI3K	0.043	0.064	0.22	7	-0.24	3	10
SOS1	0.038	0.013	-10000	0	0	56	56
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.086	0.034	-10000	0	-0.1	2	2
GRB10	0.04	0.008	-10000	0	0	23	23
activation of MAPKK activity	0.029	0.053	0.16	1	-0.26	7	8
RET51/GFRalpha1/GDNF/FRS2	0.086	0.047	-10000	0	-0.11	12	12
GAB1	0.038	0.012	-10000	0	0	52	52
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.01	-10000	0	0	33	33
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.03	0.037	-10000	0	-0.15	11	11
RET51/GFRalpha1/GDNF/PKC alpha	0.078	0.056	-10000	0	-0.11	27	27
GRB2	0.041	0.007	-10000	0	0	17	17
PRKACA	0.035	0.015	-10000	0	0	89	89
GDNF	0.039	0.011	-10000	0	0	40	40
RAC1	0.039	0.01	-10000	0	0	34	34
RET51/GFRalpha1/GDNF/IRS1	0.091	0.039	-10000	0	-0.11	5	5
Rac1/GTP	0.042	0.064	0.2	4	-0.21	4	8
RET9/GFRalpha1/GDNF	0.047	0.022	-10000	0	-0.11	1	1
GFRalpha1/GDNF	0.051	0.025	-10000	0	-0.14	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.014	0.079	-10000	0	-0.15	93	93
AKT1	0.013	0.11	0.3	9	-0.31	18	27
PTK2B	-0.012	0.077	0.2	14	-0.32	7	21
VEGFR2 homodimer/Frs2	0.033	0.057	-10000	0	-0.37	4	4
CAV1	0.036	0.015	-10000	0	0	80	80
CALM1	0.04	0.01	-10000	0	0	31	31
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.031	0.058	-10000	0	-0.36	4	4
endothelial cell proliferation	0.035	0.098	0.29	15	-0.29	9	24
mol:Ca2+	0.019	0.063	0.26	2	-0.28	8	10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.046	0.078	-10000	0	-0.21	20	20
RP11-342D11.1	-0.006	0.057	0.17	22	-0.33	5	27
CDH5	0.036	0.015	-10000	0	0	78	78
VEGFA homodimer	0.065	0.049	-10000	0	-0.11	33	33
SHC1	0.04	0.01	-10000	0	0	31	31
SHC2	0.037	0.013	-10000	0	0	64	64
HRAS/GDP	0.039	0.069	-10000	0	-0.24	11	11
SH2D2A	0.039	0.01	-10000	0	0	33	33
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.051	0.085	0.29	2	-0.32	10	12
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.035	0.053	-10000	0	-0.28	5	5
VEGFR1 homodimer	0.04	0.01	-10000	0	0	31	31
SHC/GRB2/SOS1	0.072	0.085	-10000	0	-0.25	11	11
GRB10	0.019	0.069	0.28	1	-0.34	9	10
PTPN11	0.04	0.009	-10000	0	0	27	27
GRB2	0.041	0.007	-10000	0	0	17	17
PAK1	0.037	0.014	-10000	0	0	70	70
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.051	0.089	-10000	0	-0.21	22	22
HRAS	0.04	0.01	-10000	0	0	31	31
VEGF/Rho/ROCK1/Integrin Complex	-0.014	0.11	-10000	0	-0.26	76	76
HIF1A	0.039	0.011	-10000	0	0	42	42
FRS2	0.039	0.011	-10000	0	0	40	40
oxygen and reactive oxygen species metabolic process	0.044	0.077	-10000	0	-0.21	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.04	0.008	-10000	0	0	21	21
Nck/Pak	0.036	0.056	-10000	0	-0.14	43	43
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.023	0.062	-10000	0	-0.27	7	7
mol:GDP	0.056	0.076	-10000	0	-0.24	11	11
mol:NADP	0.038	0.082	0.29	7	-0.29	12	19
eNOS/Hsp90	0.035	0.077	0.27	7	-0.28	12	19
PIK3R1	0.034	0.017	-10000	0	0	108	108
mol:IP3	0.019	0.064	0.26	2	-0.28	8	10
HIF1A/ARNT	0.05	0.045	-10000	0	-0.14	25	25
SHB	0.041	0.007	-10000	0	0	17	17
VEGFA	0.002	0.004	-10000	0	-0.037	6	6
VEGFC	0.036	0.015	-10000	0	0	80	80
FAK1/Vinculin	0.012	0.13	0.28	7	-0.29	43	50
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.041	0.007	-10000	0	0	14	14
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.023	0.088	-10000	0	-0.21	33	33
PTPN6	0.037	0.014	-10000	0	0	67	67
EPAS1	0.043	0.031	-10000	0	-0.27	3	3
mol:L-citrulline	0.038	0.082	0.29	7	-0.29	12	19
ITGAV	0.033	0.017	-10000	0	0	117	117
PIK3CA	0.03	0.019	-10000	0	0	155	155
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.054	0.07	-10000	0	-0.29	6	6
VEGFR2 homodimer/VEGFA homodimer	0.043	0.062	-10000	0	-0.29	8	8
VEGFR2/3 heterodimer	0.034	0.058	-10000	0	-0.33	5	5
VEGFB	0.039	0.011	-10000	0	0	42	42
MAPK11	-0.004	0.069	0.26	5	-0.31	9	14
VEGFR2 homodimer	0.022	0.044	-10000	0	-0.38	5	5
FLT1	0.04	0.01	-10000	0	0	31	31
NEDD4	0.041	0.014	-10000	0	-0.054	5	5
MAPK3	-0.002	0.073	0.26	10	-0.29	7	17
MAPK1	-0.002	0.074	0.27	9	-0.3	7	16
VEGFA145/NRP2	0.016	0.045	-10000	0	-0.12	49	49
VEGFR1/2 heterodimer	0.034	0.058	-10000	0	-0.29	7	7
KDR	0.022	0.044	-10000	0	-0.38	5	5
VEGFA165/NRP1/VEGFR2 homodimer	0.033	0.073	-10000	0	-0.21	20	20
SRC	0.039	0.01	-10000	0	0	36	36
platelet activating factor biosynthetic process	0	0.077	0.27	9	-0.3	7	16
PI3K	0.012	0.082	0.26	3	-0.32	9	12
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.025	0.063	-10000	0	-0.25	10	10
FES	0.02	0.065	0.26	3	-0.27	8	11
GAB1	0.019	0.083	0.26	5	-0.31	16	21
VEGFR2 homodimer/VEGFA homodimer/Src	0.035	0.053	-10000	0	-0.28	5	5
CTNNB1	0.04	0.01	-10000	0	0	31	31
SOS1	0.038	0.013	-10000	0	0	56	56
ARNT	0.041	0.006	-10000	0	0	12	12
eNOS/Caveolin-1	0.044	0.084	0.31	4	-0.3	12	16
VEGFR2 homodimer/VEGFA homodimer/Yes	0.028	0.062	-10000	0	-0.27	8	8
PI3K/GAB1	0.024	0.11	0.27	5	-0.31	20	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.048	0.084	-10000	0	-0.21	12	12
PRKACA	0.035	0.015	-10000	0	0	89	89
VEGFR2/3 heterodimer/VEGFC homodimer	0.05	0.068	-10000	0	-0.29	6	6
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.019	0.064	0.26	2	-0.34	5	7
actin cytoskeleton reorganization	0.034	0.053	-10000	0	-0.28	5	5
PTK2	-0.005	0.11	0.25	2	-0.3	38	40
EDG1	0.02	0.062	0.24	2	-0.33	5	7
mol:DAG	0.019	0.064	0.26	2	-0.28	8	10
CaM/Ca2+	0.033	0.066	0.25	2	-0.27	8	10
MAP2K3	-0.008	0.059	0.19	21	-0.33	5	26
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.047	0.073	0.24	5	-0.34	9	14
PLCG1	0.019	0.064	0.26	2	-0.29	8	10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.059	0.064	-10000	0	-0.27	5	5
IQGAP1	0.037	0.014	-10000	0	0	69	69
YES1	0.038	0.013	-10000	0	0	57	57
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.031	0.061	-10000	0	-0.28	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.033	0.053	-10000	0	-0.31	5	5
cell migration	0	0.13	0.26	8	-0.34	35	43
mol:PI-3-4-5-P3	0.012	0.078	0.25	3	-0.27	13	16
FYN	0.034	0.016	-10000	0	0	103	103
VEGFB/NRP1	0.026	0.062	0.24	3	-0.24	10	13
mol:NO	0.038	0.082	0.29	7	-0.29	12	19
PXN	0.041	0.007	-10000	0	0	14	14
HRAS/GTP	0.017	0.057	-10000	0	-0.24	11	11
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.026	0.062	-10000	0	-0.34	9	9
VHL	0.04	0.009	-10000	0	0	28	28
ITGB3	0.033	0.017	-10000	0	0	121	121
NOS3	0.038	0.087	0.3	6	-0.32	12	18
VEGFR2 homodimer/VEGFA homodimer/Sck	0.031	0.056	-10000	0	-0.32	5	5
RAC1	0.039	0.01	-10000	0	0	34	34
PRKCA	-0.008	0.065	0.19	23	-0.34	5	28
PRKCB	-0.007	0.06	0.18	24	-0.33	5	29
VCL	0.039	0.01	-10000	0	0	36	36
VEGFA165/NRP1	0.01	0.055	0.17	19	-0.26	8	27
VEGFR1/2 heterodimer/VEGFA homodimer	0.034	0.057	-10000	0	-0.28	7	7
VEGFA165/NRP2	0.016	0.045	-10000	0	-0.12	49	49
MAPKKK cascade	-0.023	0.07	0.19	24	-0.34	7	31
NRP2	0.035	0.016	-10000	0	0	94	94
VEGFC homodimer	0.036	0.015	-10000	0	0	80	80
NCK1	0.036	0.015	-10000	0	0	80	80
ROCK1	0.041	0.007	-10000	0	0	14	14
FAK1/Paxillin	0.015	0.12	0.28	7	-0.29	39	46
MAP3K13	0.014	0.062	0.26	3	-0.27	9	12
PDPK1	-0.003	0.067	0.24	3	-0.28	7	10

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.019	0.005	-10000	0	-10000	0	0
MAP4K4	-0.002	0.081	0.2	2	-0.24	31	33
BAG4	0.037	0.013	-10000	0	0	64	64
PKC zeta/ceramide	0.032	0.031	-10000	0	-0.18	8	8
NFKBIA	0.037	0.014	-10000	0	0	66	66
BIRC3	0.026	0.02	-10000	0	0	218	218
BAX	0.012	0.058	-10000	0	-0.34	14	14
RIPK1	0.038	0.012	-10000	0	0	48	48
AKT1	0.001	0.12	0.67	17	-10000	0	17
BAD	0.001	0.03	0.18	4	-0.18	8	12
SMPD1	0.01	0.06	0.16	17	-0.17	25	42
RB1	-0.006	0.038	0.22	2	-0.18	8	10
FADD/Caspase 8	-0.004	0.11	0.25	8	-0.3	40	48
MAP2K4	-0.006	0.028	-10000	0	-0.18	7	7
NSMAF	0.038	0.012	-10000	0	0	54	54
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.005	0.033	0.18	7	-0.18	8	15
EGF	0.038	0.012	-10000	0	0	53	53
mol:ceramide	0.006	0.027	-10000	0	-0.19	8	8
MADD	0.041	0.006	-10000	0	0	11	11
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.016	0.009	-10000	0	-10000	0	0
ASAH1	0.032	0.018	-10000	0	0	128	128
negative regulation of cell cycle	-0.006	0.038	0.22	2	-0.18	8	10
cell proliferation	0.026	0.051	0.2	5	-0.18	7	12
BID	0.02	0.095	-10000	0	-0.5	7	7
MAP3K1	-0.001	0.027	-10000	0	-0.18	7	7
EIF2A	0.009	0.079	0.18	74	-0.2	9	83
TRADD	0.036	0.014	-10000	0	0	76	76
CRADD	0.041	0.006	-10000	0	0	13	13
MAPK3	-0.003	0.037	0.17	6	-0.19	7	13
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.009	0.044	0.17	6	-0.17	7	13
Cathepsin D/ceramide	0.03	0.032	-10000	0	-0.17	9	9
FADD	-0.001	0.084	0.21	6	-0.25	29	35
KSR1	-0.001	0.026	-10000	0	-0.18	8	8
MAPK8	0.008	0.048	-10000	0	-0.21	14	14
PRKRA	0.004	0.044	0.2	17	-0.18	7	24
PDGFA	0.041	0.007	-10000	0	0	18	18
TRAF2	0.04	0.009	-10000	0	0	29	29
IGF1	0.036	0.015	-10000	0	0	84	84
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.006	0.027	-10000	0	-0.19	8	8
CTSD	0.038	0.012	-10000	0	0	54	54
regulation of nitric oxide biosynthetic process	0.043	0.05	-10000	0	-0.14	36	36
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.029	0.054	0.21	5	-0.2	7	12
PRKCD	0.038	0.013	-10000	0	0	56	56
PRKCZ	0.042	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.016	0.009	-10000	0	-10000	0	0
RelA/NF kappa B1	0.043	0.05	-10000	0	-0.14	36	36
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.041	0.007	-10000	0	0	18	18
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.005	0.086	-10000	0	-0.26	30	30
TNFR1A/BAG4/TNF-alpha	0.059	0.046	-10000	0	-0.12	15	15
mol:Sphingosine-1-phosphate	-0.019	0.005	-10000	0	-10000	0	0
MAP2K1	-0.009	0.036	0.17	11	-0.18	6	17
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
CYCS	0.009	0.05	0.14	3	-0.19	11	14
TNFRSF1A	0.036	0.015	-10000	0	0	84	84
NFKB1	0.036	0.015	-10000	0	0	84	84
TNFR1A/BAG4	0.044	0.038	-10000	0	-0.13	14	14
EIF2AK2	-0.001	0.057	0.19	30	-0.17	11	41
TNF-alpha/TNFR1A/FAN	0.059	0.052	-10000	0	-0.14	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.14	-10000	0	-0.37	55	55
MAP2K2	-0.008	0.033	0.17	6	-0.18	7	13
SMPD3	-0.004	0.1	0.19	6	-0.29	54	60
TNF	0.04	0.009	-10000	0	0	26	26
PKC zeta/PAR4	0.06	0.016	-10000	0	-0.14	2	2
mol:PHOSPHOCHOLINE	0.004	0.035	0.12	3	-0.14	8	11
NF kappa B1/RelA/I kappa B alpha	0.081	0.083	-10000	0	-0.12	62	62
AIFM1	0.01	0.042	0.12	5	-0.17	11	16
BCL2	0.036	0.014	-10000	0	0	76	76

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.047	0.045	-9999	-0.14	27	27
FBXW11	0.04	0.009	-9999	0	25	25
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.009	-9999	0	25	25
CHUK	0.038	0.012	-9999	0	52	52
NF kappa B2 p100/RelB	0.094	0.067	-9999	-0.12	30	30
NFKB1	0.036	0.015	-9999	0	84	84
MAP3K14	0.04	0.009	-9999	0	29	29
NF kappa B1 p50/RelB	0.042	0.05	-9999	-0.14	35	35
RELB	0.04	0.009	-9999	0	27	27
NFKB2	0.04	0.009	-9999	0	24	24
NF kappa B2 p52/RelB	0.051	0.022	-9999	-0.13	4	4
regulation of B cell activation	0.05	0.022	-9999	-0.13	4	4

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.049	0.045	0.15	18	-10000	0	18
KIRREL	0.041	0.017	0.084	2	-0.037	2	4
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.049	0.045	-10000	0	-0.15	18	18
PLCG1	0.038	0.012	-10000	0	0	50	50
ARRB2	0.039	0.011	-10000	0	0	44	44
WASL	0.04	0.009	-10000	0	0	24	24
Nephrin/NEPH1/podocin/CD2AP	0.073	0.071	-10000	0	-0.12	41	41
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.031	0.057	-10000	0	-0.15	15	15
FYN	0.003	0.065	0.17	60	-0.18	3	63
mol:Ca2+	0.075	0.064	-10000	0	-0.13	25	25
mol:DAG	0.077	0.065	-10000	0	-0.13	25	25
NPHS2	0.043	0.02	-10000	0	-0.043	19	19
mol:IP3	0.077	0.065	-10000	0	-0.13	25	25
regulation of endocytosis	0.053	0.059	-10000	0	-0.12	20	20
Nephrin/NEPH1/podocin/Cholesterol	0.064	0.048	0.18	1	-0.11	18	19
establishment of cell polarity	0.049	0.045	-10000	0	-0.15	18	18
Nephrin/NEPH1/podocin/NCK1-2	0.086	0.078	-10000	0	-0.12	31	31
Nephrin/NEPH1/beta Arrestin2	0.056	0.06	-10000	0	-0.12	20	20
NPHS1	0.04	0.022	-10000	0	-0.044	17	17
Nephrin/NEPH1/podocin	0.055	0.056	0.22	1	-0.12	19	20
TJP1	0.037	0.013	-10000	0	0	64	64
NCK1	0.036	0.015	-10000	0	0	80	80
NCK2	0.042	0.004	-10000	0	0	6	6
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.078	0.066	-10000	0	-0.13	25	25
CD2AP	0.037	0.014	-10000	0	0	67	67
Nephrin/NEPH1/podocin/GRB2	0.085	0.059	-10000	0	-0.12	18	18
GRB2	0.041	0.007	-10000	0	0	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.005	0.071	0.17	68	-0.12	3	71
cytoskeleton organization	0.013	0.054	0.25	4	-0.16	13	17
Nephrin/NEPH1	0.042	0.034	-10000	0	-0.096	18	18
Nephrin/NEPH1/ZO-1	0.055	0.062	-10000	0	-0.13	37	37

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.06	0.041	-10000	0	-0.11	9	9
TC10/GTP	0.05	0.036	-10000	0	-0.1	10	10
Insulin Receptor/Insulin/IRS1/Shp2	0.089	0.058	-10000	0	-0.12	23	23
HRAS	0.04	0.01	-10000	0	0	31	31
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.038	0.012	-10000	0	0	53	53
FOXO3	-0.005	0.009	0.022	10	-0.037	5	15
AKT1	0.016	0.098	0.24	33	-0.18	3	36
INSR	0.042	0.016	0.082	13	-10000	0	13
Insulin Receptor/Insulin	0.081	0.053	0.24	28	-0.1	3	31
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.04	0.008	-10000	0	0	23	23
SORBS1	0.039	0.011	-10000	0	0	40	40
CRK	0.038	0.012	-10000	0	0	52	52
PTPN1	-0.005	0.042	0.15	36	-10000	0	36
CAV1	-0.007	0.042	0.17	18	-10000	0	18
CBL/APS/CAP/Crk-II/C3G	0.08	0.043	-10000	0	-0.11	6	6
Insulin Receptor/Insulin/IRS1/NCK2	0.096	0.046	-10000	0	-0.11	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.041	0.064	-10000	0	-0.11	45	45
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.026	0.097	0.22	1	-0.31	36	37
RPS6KB1	0.005	0.09	0.2	42	-0.18	8	50
PARD6A	0.036	0.015	-10000	0	0	81	81
CBL	0.04	0.008	-10000	0	0	23	23
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.022	0.081	-10000	0	-0.69	7	7
PIK3R1	0.034	0.017	-10000	0	0	108	108
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.049	0.082	0.2	20	-0.17	14	34
HRAS/GTP	-0.026	0.033	0.049	1	-0.11	21	22
Insulin Receptor	0.042	0.016	0.082	13	-10000	0	13
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.1	0.062	-10000	0	-0.11	11	11
PRKCI	-0.006	0.13	-10000	0	-0.39	51	51
Insulin Receptor/Insulin/GRB14/PDK1	0.02	0.053	-10000	0	-0.12	44	44
SHC1	0.04	0.01	-10000	0	0	31	31
negative regulation of MAPKKK cascade	0.046	0.084	-10000	0	-0.56	7	7
PI3K	0.051	0.073	-10000	0	-0.11	43	43
NCK2	0.042	0.004	-10000	0	0	6	6
RHOQ	0.039	0.01	-10000	0	0	33	33
mol:H2O2	-0.001	0.005	0.035	3	-10000	0	3
HRAS/GDP	0.029	0.01	-10000	0	-0.13	1	1
AKT2	0.015	0.095	0.22	37	-0.18	3	40
PRKCZ	0.036	0.09	-10000	0	-0.32	26	26
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.007	0.041	0.15	18	-10000	0	18
F2RL2	0.036	0.014	-10000	0	0	73	73
TRIP10	0.038	0.012	-10000	0	0	47	47
Insulin Receptor/Insulin/Shc	0.07	0.037	-10000	0	-0.098	5	5
TC10/GTP/CIP4/Exocyst	0.047	0.029	-10000	0	-0.11	12	12
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.093	0.071	-10000	0	-0.12	25	25
RAPGEF1	0.04	0.008	-10000	0	0	23	23
RASA1	0.037	0.014	-10000	0	0	71	71
NCK1	0.036	0.015	-10000	0	0	80	80
CBL/APS/CAP/Crk-II	0.065	0.036	-10000	0	-0.12	6	6
TC10/GDP	0.027	0.02	-10000	0	-0.13	8	8
Insulin Receptor/Insulin/SHC/GRB10	0.088	0.053	-10000	0	-0.11	11	11
INPP5D	-0.012	0.019	0.045	27	-0.094	7	34
SOS1	0.038	0.013	-10000	0	0	56	56
SGK1	-0.004	0.004	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.04	0.009	-10000	0	0	27	27
IRS1	0.04	0.008	-10000	0	0	22	22
p62DOK/RasGAP	0.047	0.085	-10000	0	-0.56	7	7
INS	0.044	0.014	0.083	18	-10000	0	18
mol:PI-3-4-P2	-0.012	0.019	0.045	27	-0.094	7	34
GRB2	0.041	0.007	-10000	0	0	17	17
EIF4EBP1	0.003	0.08	0.18	33	-0.17	2	35
PTPRA	0.042	0.014	0.082	5	-10000	0	5
PIK3CA	0.03	0.019	-10000	0	0	155	155
TC10/GTP/CIP4	0.047	0.029	-10000	0	-0.11	12	12
PDPK1	0.04	0.009	-10000	0	0	25	25
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.029	0.059	0.16	1	-0.15	30	31
Insulin Receptor/Insulin/IRS1	0.071	0.038	-10000	0	-0.099	8	8
Insulin Receptor/Insulin/IRS3	0.059	0.03	-10000	0	-0.14	3	3
Par3/Par6	0.067	0.051	-10000	0	-0.1	14	14

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.09	0.05	-10000	0	-0.11	20	20
HDAC3	0.041	0.007	-10000	0	0	15	15
Ran/GTP/Exportin 1/HDAC4	-0.027	0.024	-10000	0	-0.12	33	33
GATA1/HDAC4	0.06	0.01	-10000	0	-10000	0	0
GATA1/HDAC5	0.059	0.015	-10000	0	-10000	0	0
GATA2/HDAC5	0.055	0.02	-10000	0	-10000	0	0
HDAC5/BCL6/BCoR	0.051	0.059	-10000	0	-0.12	36	36
HDAC9	0.035	0.015	-10000	0	0	88	88
Glucocorticoid receptor/Hsp90/HDAC6	0.045	0.039	-10000	0	-0.11	30	30
HDAC4/ANKRA2	0.049	0.033	-10000	0	-0.14	9	9
HDAC5/YWHAB	0.051	0.03	-10000	0	-0.14	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.035	-10000	0	-0.15	25	25
GATA2	0.039	0.01	-10000	0	0	35	35
HDAC4/RFXANK	0.047	0.041	-10000	0	-0.14	20	20
BCOR	0.041	0.005	-10000	0	0	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.031	0.018	-10000	0	0	141	141
HDAC5	0.04	0.01	-10000	0	0	32	32
GNB1/GNG2	0.053	0.038	-10000	0	-0.14	19	19
Histones	-0.006	0.071	-10000	0	-0.19	39	39
ADRBK1	0.041	0.005	-10000	0	0	7	7
HDAC4	0.041	0.007	-10000	0	0	15	15
XPO1	0.039	0.011	-10000	0	0	39	39
HDAC5/ANKRA2	0.048	0.033	-10000	0	-0.13	9	9
HDAC4/Ubc9	0.057	0.018	-10000	0	-0.14	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.052	0.03	-10000	0	-0.14	8	8
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.041	0.007	-10000	0	0	15	15
HDAC5/RFXANK	0.046	0.042	-10000	0	-0.14	21	21
CAMK4	0.037	0.013	-10000	0	0	64	64
Tubulin/HDAC6	0.05	0.018	-10000	0	-10000	0	0
SUMO1	0.041	0.006	-10000	0	0	13	13
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.038	0.012	-10000	0	0	52	52
GATA1	0.042	0.002	-10000	0	0	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.038	0.013	-10000	0	0	58	58
NR3C1	0.039	0.012	-10000	0	0	46	46
SUMO1/HDAC4	0.041	0.062	-10000	0	-0.18	18	18
SRF	0.039	0.011	-10000	0	0	42	42
HDAC4/YWHAB	0.053	0.029	-10000	0	-0.14	7	7
Tubulin	0.028	0.009	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.052	0.03	-10000	0	-0.14	8	8
GNB1	0.041	0.005	-10000	0	0	7	7
RANGAP1	0.038	0.013	-10000	0	0	57	57
BCL6/BCoR	0.036	0.053	-10000	0	-0.14	36	36
HDAC4/HDAC3/SMRT (N-CoR2)	0.075	0.033	-10000	0	-0.12	7	7
HDAC4/SRF	0.068	0.034	-10000	0	-0.12	1	1
HDAC4/ER alpha	0.04	0.054	-10000	0	-0.14	43	43
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.006	0.07	-10000	0	-0.19	39	39
cell motility	0.05	0.017	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.04	0.009	-10000	0	0	27	27
HDAC7/HDAC3	0.029	0.012	-10000	0	-0.13	3	3
BCL6	0.031	0.018	-10000	0	0	146	146
HDAC4/CaMK II delta B	0.041	0.007	-10000	0	0	15	15
Hsp90/HDAC6	0.03	0.005	-10000	0	-10000	0	0
ESR1	0.035	0.016	-10000	0	0	92	92
HDAC6/HDAC11	0.056	0.026	-10000	0	-0.14	7	7
Ran/GTP/Exportin 1	0.038	0.071	0.18	1	-0.2	26	27
NPC	0.02	0.022	-10000	0	-0.085	23	23
MEF2C	0.036	0.014	-10000	0	0	75	75
RAN	0.041	0.006	-10000	0	0	13	13
HDAC4/MEF2C	0.094	0.063	-10000	0	-0.12	18	18
GNG2	0.039	0.01	-10000	0	0	34	34
NCOR2	0.04	0.009	-10000	0	0	28	28
TUBB2A	0.038	0.012	-10000	0	0	47	47
HDAC11	0.04	0.008	-10000	0	0	23	23
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.04	0.009	-10000	0	0	30	30
ANKRA2	0.035	0.015	-10000	0	0	87	87
RFXANK	0.036	0.014	-10000	0	0	77	77
nuclear import	-0.036	0.041	0.18	14	-10000	0	14

×

IL27-mediated signaling events

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
TGFB1	0.037	0.013	-10000	0	0	62	62
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.003	0.11	0.53	9	-10000	0	9
IL27/IL27R/JAK1	0.08	0.12	-10000	0	-0.91	3	3
TBX21	0.004	0.1	0.36	5	-0.57	3	8
IL12B	0.042	0.008	-10000	0	0	20	20
IL12A	-0.006	0.006	0.013	26	-10000	0	26
IL6ST	0.036	0.018	-10000	0	-0.032	2	2
IL27RA/JAK1	0.049	0.11	-10000	0	-1.1	3	3
IL27	0.043	0.009	-10000	0	-0.036	3	3
TYK2	0.039	0.016	-10000	0	-0.036	3	3
T-helper cell lineage commitment	0.006	0.061	0.2	20	-0.18	31	51
T-helper 2 cell differentiation	-0.003	0.11	0.53	9	-10000	0	9
T cell proliferation during immune response	-0.003	0.11	0.53	9	-10000	0	9
MAPKKK cascade	0.003	0.11	-10000	0	-0.53	9	9
STAT3	0.038	0.013	-10000	0	0	56	56
STAT2	0.039	0.011	-10000	0	0	43	43
STAT1	0.034	0.017	-10000	0	0	108	108
IL12RB1	0.039	0.012	-10000	0	0	49	49
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.002	0.1	0.36	2	-0.55	3	5
IL27/IL27R/JAK2/TYK2	0.003	0.12	-10000	0	-0.54	9	9
positive regulation of T cell mediated cytotoxicity	0.003	0.11	-10000	0	-0.53	9	9
STAT1 (dimer)	0.063	0.13	-10000	0	-0.81	3	3
JAK2	0.037	0.018	-10000	0	-0.037	1	1
JAK1	0.039	0.01	-10000	0	0	34	34
STAT2 (dimer)	0.02	0.13	-10000	0	-0.49	11	11
T cell proliferation	0.005	0.11	0.34	2	-0.51	9	11
IL12/IL12R/TYK2/JAK2	0.015	0.17	-10000	0	-0.7	26	26
IL17A	0.008	0.056	0.2	18	-0.18	26	44
mast cell activation	-0.003	0.11	0.53	9	-10000	0	9
IFNG	0.013	0.03	0.1	1	-0.098	6	7
T cell differentiation	-0.001	0.003	0.014	1	-0.022	3	4
STAT3 (dimer)	0.025	0.13	-10000	0	-0.43	14	14
STAT5A (dimer)	0.025	0.13	-10000	0	-0.52	9	9
STAT4 (dimer)	0.024	0.13	-10000	0	-0.51	9	9
STAT4	0.04	0.009	-10000	0	0	29	29
T cell activation	-0.008	0.011	0.12	1	-0.046	33	34
IL27R/JAK2/TYK2	0.053	0.1	-10000	0	-0.94	3	3
GATA3	0.015	0.12	0.63	19	-10000	0	19
IL18	-0.006	0.006	0.002	178	-10000	0	178
positive regulation of mast cell cytokine production	0.025	0.13	-10000	0	-0.42	14	14
IL27/EBI3	0.059	0.022	-10000	0	-10000	0	0
IL27RA	0.024	0.12	-10000	0	-1.1	3	3
IL6	0.034	0.017	-10000	0	0	111	111
STAT5A	0.038	0.012	-10000	0	0	51	51
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.008	0.042	0.48	3	-10000	0	3
IL1B	-0.007	0.006	0.002	149	-10000	0	149
EBI3	0.039	0.014	-10000	0	-0.037	1	1
TNF	-0.008	0.005	0.006	65	-10000	0	65

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.015	0.17	-10000	0	-0.68	14	14
NCK1/PAK1/Dok-R	-0.029	0.072	-10000	0	-0.33	15	15
NCK1/Dok-R	0.05	0.098	-10000	0	-0.88	2	2
PIK3CA	0.03	0.019	-10000	0	0	155	155
mol:beta2-estradiol	-0.008	0.008	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
SHC1	0.04	0.01	-10000	0	0	31	31
Rac/GDP	0.029	0.01	-10000	0	-0.13	1	1
F2	0.01	0.038	-10000	0	-0.079	4	4
TNIP2	0.038	0.012	-10000	0	0	49	49
NF kappa B/RelA	0.076	0.1	-10000	0	-0.84	2	2
FN1	0.021	0.021	-10000	0	0	277	277
PLD2	0.033	0.077	-10000	0	-0.9	2	2
PTPN11	0.04	0.009	-10000	0	0	27	27
GRB14	0.038	0.012	-10000	0	0	53	53
ELK1	0.032	0.078	-10000	0	-0.85	2	2
GRB7	0.037	0.013	-10000	0	0	63	63
PAK1	0.037	0.014	-10000	0	0	70	70
Tie2/Ang1/alpha5/beta1 Integrin	0.037	0.12	-10000	0	-0.86	2	2
CDKN1A	0.014	0.19	-10000	0	-0.62	39	39
ITGA5	0.038	0.013	-10000	0	0	58	58
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.054	0.096	-10000	0	-0.88	2	2
CRK	0.038	0.012	-10000	0	0	52	52
mol:NO	0.03	0.15	0.37	1	-0.51	15	16
PLG	0.031	0.076	-10000	0	-0.9	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.027	0.14	-10000	0	-0.75	6	6
GRB2	0.041	0.007	-10000	0	0	17	17
PIK3R1	0.034	0.017	-10000	0	0	108	108
ANGPT2	-0.045	0.29	-10000	0	-1	38	38
BMX	0.032	0.077	-10000	0	-0.9	2	2
ANGPT1	0.03	0.054	-10000	0	-10000	0	0
tube development	-0.002	0.21	-10000	0	-0.7	39	39
ANGPT4	0.035	0.021	-10000	0	-0.012	82	82
response to hypoxia	0.001	0.008	0.033	1	-0.062	2	3
Tie2/Ang1/GRB14	0.054	0.089	-10000	0	-0.91	2	2
alpha5/beta1 Integrin	0.046	0.045	-10000	0	-0.14	27	27
FGF2	0.039	0.012	-10000	0	0	45	45
STAT5A (dimer)	0.015	0.24	-10000	0	-0.8	39	39
mol:L-citrulline	0.03	0.15	0.37	1	-0.51	15	16
AGTR1	0.033	0.025	-10000	0	-0.047	35	35
MAPK14	0.041	0.12	-10000	0	-1	4	4
Tie2/SHP2	0.038	0.11	-10000	0	-0.65	4	4
TEK	0.03	0.11	-10000	0	-0.69	4	4
RPS6KB1	0.016	0.16	-10000	0	-0.66	11	11
Angiotensin II/AT1	0.025	0.024	-10000	0	-0.057	35	35
Tie2/Ang1/GRB2	0.058	0.091	-10000	0	-0.91	2	2
MAPK3	0.028	0.075	-10000	0	-0.85	2	2
MAPK1	0.027	0.074	-10000	0	-0.85	2	2
Tie2/Ang1/GRB7	0.054	0.09	-10000	0	-0.91	2	2
NFKB1	0.036	0.015	-10000	0	0	84	84
MAPK8	0.031	0.08	-10000	0	-0.9	2	2
PI3K	0.017	0.16	-10000	0	-0.82	8	8
FES	0.043	0.11	-10000	0	-1	2	2
Crk/Dok-R	0.056	0.095	-10000	0	-0.88	2	2
Tie2/Ang1/ABIN2	0.056	0.091	-10000	0	-0.91	2	2
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.019	0.16	-10000	0	-0.61	15	15
STAT5A	0.038	0.012	-10000	0	0	51	51
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.061	0.18	-10000	0	-0.67	8	8
Tie2/Ang2	-0.013	0.27	-10000	0	-0.95	39	39
Tie2/Ang1	0.043	0.082	-10000	0	-0.94	2	2
FOXO1	0.015	0.18	-10000	0	-0.6	39	39
ELF1	0.047	0.019	-10000	0	-0.13	2	2
ELF2	0.04	0.079	-10000	0	-0.9	2	2
mol:Choline	0.033	0.076	-10000	0	-0.87	2	2
cell migration	-0.017	0.047	-10000	0	-0.18	15	15
FYN	-0.01	0.23	-10000	0	-0.8	39	39
DOK2	0.032	0.018	-10000	0	0	135	135
negative regulation of cell cycle	0.017	0.18	-10000	0	-0.56	39	39
ETS1	0.043	0.021	-10000	0	-10000	0	0
PXN	0.061	0.17	0.4	1	-0.57	8	9
ITGB1	0.039	0.011	-10000	0	0	38	38
NOS3	0.026	0.16	-10000	0	-0.58	14	14
RAC1	0.039	0.01	-10000	0	0	34	34
TNF	0.049	0.014	-10000	0	-10000	0	0
MAPKKK cascade	0.033	0.076	-10000	0	-0.87	2	2
RASA1	0.037	0.014	-10000	0	0	71	71
Tie2/Ang1/Shc	0.059	0.091	-10000	0	-0.91	2	2
NCK1	0.036	0.015	-10000	0	0	80	80
vasculogenesis	0.031	0.14	0.36	3	-0.42	24	27
mol:Phosphatidic acid	0.033	0.076	-10000	0	-0.87	2	2
mol:Angiotensin II	0	0.008	-10000	0	-0.033	30	30
mol:NADP	0.03	0.15	0.37	1	-0.51	15	16
Rac1/GTP	0.029	0.15	-10000	0	-0.67	8	8
MMP2	0.033	0.087	-10000	0	-0.9	2	2

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.02	0.075	-10000	0	-0.47	5	5
SMARCC2	0.04	0.009	-10000	0	0	25	25
SMARCC1	0.04	0.008	-10000	0	0	21	21
TBX21	0.04	0.058	0.41	1	-10000	0	1
SUMO2	0.037	0.015	-10000	0	-0.03	20	20
STAT1 (dimer)	0.022	0.064	-10000	0	-0.18	46	46
FKBP4	0.036	0.015	-10000	0	0	86	86
FKBP5	0.031	0.018	-10000	0	0	147	147
GR alpha/HSP90/FKBP51/HSP90	-0.035	0.074	0.2	2	-0.21	19	21
PRL	0.049	0.068	0.39	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.059	0.12	0.38	3	-0.35	1	4
RELA	0.013	0.097	-10000	0	-0.16	126	126
FGG	-0.055	0.11	0.33	3	-0.32	1	4
GR beta/TIF2	-0.033	0.079	0.22	2	-0.24	7	9
IFNG	0.047	0.1	-10000	0	-10000	0	0
apoptosis	-0.055	0.17	-10000	0	-0.46	37	37
CREB1	0.049	0.009	-10000	0	-10000	0	0
histone acetylation	0.022	0.083	0.29	10	-0.39	6	16
BGLAP	0.045	0.091	-10000	0	-0.89	3	3
GR/PKAc	0.032	0.085	-10000	0	-0.16	24	24
NF kappa B1 p50/RelA	0.01	0.17	-10000	0	-0.3	115	115
SMARCD1	0.041	0.008	-10000	0	0	19	19
MDM2	-0.013	0.047	0.14	4	-0.24	7	11
GATA3	0.05	0.014	-10000	0	-10000	0	0
AKT1	0.035	0.016	0.17	2	-0.052	7	9
CSF2	0.012	0.054	-10000	0	-10000	0	0
GSK3B	0.037	0.015	-10000	0	-0.03	17	17
NR1I3	-0.043	0.16	-10000	0	-0.5	6	6
CSN2	-0.05	0.097	0.28	3	-0.31	1	4
BRG1/BAF155/BAF170/BAF60A	0.077	0.065	-10000	0	-0.13	32	32
NFATC1	0.043	0.017	-10000	0	-10000	0	0
POU2F1	0.046	0.01	-10000	0	-10000	0	0
CDKN1A	-0.041	0.12	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.005	-10000	0	-10000	0	0
SFN	0.036	0.015	-10000	0	0	86	86
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.025	0.082	0.22	1	-0.2	28	29
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.11	0.28	-10000	0	-0.7	92	92
JUN	0.041	0.098	0.34	9	-0.28	3	12
IL4	0.042	0.057	-10000	0	-10000	0	0
CDK5R1	0.039	0.01	-10000	0	0	30	30
PRKACA	0.035	0.015	-10000	0	0	89	89
cortisol/GR alpha (monomer)/AP-1	-0.041	0.07	0.2	13	-0.22	25	38
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.017	0.081	0.22	1	-0.2	20	21
cortisol/GR alpha (monomer)	-0.071	0.13	0.4	4	-0.4	1	5
NCOA2	0.037	0.014	-10000	0	0	71	71
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.032	0.054	-10000	0	-0.12	30	30
AP-1/NFAT1-c-4	0.039	0.14	-10000	0	-0.37	20	20
AFP	0.03	0.095	-10000	0	-10000	0	0
SUV420H1	0.04	0.009	-10000	0	0	30	30
IRF1	-0.1	0.22	-10000	0	-0.58	83	83
TP53	0.036	0.028	-10000	0	-10000	0	0
PPP5C	0.04	0.01	-10000	0	0	32	32
KRT17	0.029	0.16	-10000	0	-0.72	12	12
KRT14	0.026	0.17	0.5	8	-1.1	10	18
TBP	0.044	0.032	-10000	0	-0.34	3	3
CREBBP	0.029	0.051	0.34	11	-10000	0	11
HDAC1	0.033	0.012	-10000	0	-0.059	2	2
HDAC2	0.037	0.011	-10000	0	-10000	0	0
AP-1	0.038	0.14	-10000	0	-0.38	20	20
MAPK14	0.037	0.016	-10000	0	-0.03	19	19
MAPK10	0.033	0.021	-10000	0	-0.03	30	30
MAPK11	0.029	0.021	-10000	0	-0.03	16	16
KRT5	-0.006	0.26	-10000	0	-0.83	44	44
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.041	0.012	-10000	0	-0.068	2	2
STAT1	0.022	0.064	-10000	0	-0.18	46	46
CGA	0.046	0.064	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.061	0.11	0.31	2	-0.36	36	38
MAPK3	0.036	0.019	-10000	0	-0.03	34	34
MAPK1	0.035	0.018	-10000	0	-0.03	21	21
ICAM1	-0.076	0.32	-10000	0	-0.77	93	93
NFKB1	0.006	0.11	-10000	0	-0.2	112	112
MAPK8	0.049	0.083	0.57	1	-0.23	4	5
MAPK9	0.036	0.017	-10000	0	-0.031	22	22
cortisol/GR alpha (dimer)	-0.057	0.18	-10000	0	-0.48	37	37
BAX	-0.048	0.12	-10000	0	-10000	0	0
POMC	0.056	0.094	0.51	1	-10000	0	1
EP300	0.027	0.047	0.33	9	-0.06	44	53
cortisol/GR alpha (dimer)/p53	-0.078	0.12	0.38	3	-10000	0	3
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.047	0.25	5	-0.22	7	12
SGK1	-0.025	0.11	0.34	9	-0.29	50	59
IL13	0.049	0.092	-10000	0	-0.46	1	1
IL6	0.013	0.16	-10000	0	-0.62	18	18
PRKACG	0.041	0.005	-10000	0	0	9	9
IL5	0.048	0.096	-10000	0	-10000	0	0
IL2	0.038	0.12	-10000	0	-0.53	5	5
CDK5	0.035	0.015	-10000	0	0	83	83
PRKACB	0.038	0.012	-10000	0	0	48	48
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.013	0.23	-10000	0	-0.79	37	37
CDK5R1/CDK5	0.045	0.041	-10000	0	-0.13	20	20
NF kappa B1 p50/RelA/PKAc	0.043	0.15	-10000	0	-0.22	93	93
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.36	4	-0.32	1	5
SMARCA4	0.035	0.015	-10000	0	0	90	90
chromatin remodeling	-0.03	0.092	0.28	2	-0.36	10	12
NF kappa B1 p50/RelA/Cbp	0.024	0.16	0.42	6	-0.25	107	113
JUN (dimer)	0.04	0.098	0.34	9	-0.28	3	12
YWHAH	0.037	0.013	-10000	0	0	60	60
VIPR1	0.041	0.057	0.4	1	-10000	0	1
NR3C1	-0.047	0.092	0.27	2	-0.32	6	8
NR4A1	0.038	0.018	-10000	0	-10000	0	0
TIF2/SUV420H1	0.042	0.052	-10000	0	-0.14	36	36
MAPKKK cascade	-0.055	0.17	-10000	0	-0.46	37	37
cortisol/GR alpha (dimer)/Src-1	-0.055	0.12	0.38	4	-10000	0	4
PBX1	0.044	0.013	-10000	0	-10000	0	0
POU1F1	0.046	0.009	-10000	0	-10000	0	0
SELE	0.022	0.12	-10000	0	-0.37	4	4
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.031	0.092	0.28	2	-0.36	10	12
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.36	4	-0.32	1	5
mol:cortisol	-0.043	0.066	0.21	3	-10000	0	3
MMP1	0.009	0.18	-10000	0	-0.8	21	21

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.036	0.014	-10000	0	0	73	73
HDAC4	0.041	0.007	-10000	0	0	15	15
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.013	0.004	-10000	0	-10000	0	0
CDKN1A	0.024	0.066	0.29	19	-10000	0	19
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.04	0.008	-10000	0	0	22	22
FOXO3	0.002	0.042	0.25	15	-10000	0	15
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.005	0.035	-10000	0	-0.18	19	19
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.037	0.014	-10000	0	0	70	70
TAT	0.036	0.014	-10000	0	0	75	75
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.01	0.002	-10000	0	-10000	0	0
PPARGC1A	0.038	0.012	-10000	0	0	55	55
FHL2	0.04	0.008	-10000	0	0	20	20
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.046	0.041	-10000	0	-0.17	15	15
HIST2H4A	-0.013	0.004	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.036	0.048	0.15	58	-0.21	6	64
SIRT1	0.037	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.072	0.034	-10000	0	-0.12	8	8
SIRT1/Histone H1b	0.005	0.091	-10000	0	-0.2	68	68
apoptosis	-0.064	0.045	0.14	15	-10000	0	15
SIRT1/PGC1A	0.046	0.026	-10000	0	-0.11	8	8
p53/SIRT1	-0.01	0.09	-10000	0	-0.15	163	163
SIRT1/FOXO4	0.009	0.075	-10000	0	-0.15	84	84
FOXO1/FHL2/SIRT1	0.046	0.025	-10000	0	-0.1	12	12
HIST1H1E	-0.005	0.07	-10000	0	-0.21	53	53
SIRT1/p300	0.044	0.042	-10000	0	-0.14	23	23
muscle cell differentiation	-0.018	0.023	0.11	9	-0.21	2	11
TP53	0.024	0.019	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.065	0.046	-10000	0	-0.14	15	15
CREBBP	0.038	0.012	-10000	0	0	54	54
MEF2D	0.04	0.009	-10000	0	0	28	28
HIV-1 Tat/SIRT1	0.048	0.031	-10000	0	-0.13	8	8
ACSS2	-0.021	0.009	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.018	0.024	0.21	2	-0.11	9	11

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.02	0.024	0.21	3	-0.11	2	5
NFATC2	0.021	0.024	0.22	3	-0.11	3	6
NFATC3	0.021	0.024	0.2	3	-0.11	2	5
CD40LG	0.034	0.1	0.31	16	-0.24	1	17
PTGS2	0.014	0.09	0.34	8	-0.27	5	13
JUNB	0.03	0.019	-10000	0	0	160	160
CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.017	-10000	0	-0.13	3	3
CaM/Ca2+	0.032	0.017	-10000	0	-0.13	3	3
CALM1	0.042	0.011	-10000	0	-0.001	32	32
JUN	0.038	0.016	0.099	1	0	81	82
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.027	0.012	-10000	0	-0.1	2	2
FOSL1	0.041	0.007	-10000	0	0	15	15
CREM	0.04	0.008	-10000	0	0	20	20
Jun/NFAT1-c-4/p21SNFT	0.056	0.069	0.24	8	-10000	0	8
FOS	0.028	0.022	0.099	1	0	207	208
IFNG	0.024	0.097	0.32	13	-0.24	1	14
AP-1/NFAT1-c-4	0.084	0.12	-10000	0	-0.23	3	3
FASLG	0.031	0.1	0.32	14	-0.24	2	16
NFAT1-c-4/ICER1	0.053	0.058	0.22	7	-10000	0	7
IL2RA	0.031	0.1	0.33	14	-0.25	2	16
FKBP12/FK506	0.028	0.013	-10000	0	-0.13	2	2
CSF2	0.033	0.1	0.32	15	-0.24	1	16
JunB/Fra1/NFAT1-c-4	0.048	0.074	0.23	4	-0.18	3	7
IL4	0.032	0.1	0.3	19	-0.24	1	20
IL2	-0.039	0.23	-10000	0	-0.86	41	41
IL3	0.026	0.12	-10000	0	-0.58	21	21
FKBP1A	0.038	0.012	-10000	0	0	50	50
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.046	0.01	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.015	0.12	-10000	0	-0.85	9	9
MKNK1	0.04	0.009	-10000	0	0	25	25
MAPK14	0.042	0.053	0.17	1	-0.14	32	33
ATF2/c-Jun	-0.02	0.1	-10000	0	-0.31	43	43
MAPK11	0.031	0.054	-10000	0	-0.14	31	31
MITF	0.019	0.061	-10000	0	-0.28	16	16
MAPKAPK5	0.019	0.058	-10000	0	-0.26	17	17
KRT8	0.016	0.061	-10000	0	-0.23	24	24
MAPKAPK3	0.041	0.006	-10000	0	0	13	13
MAPKAPK2	0.04	0.008	-10000	0	0	23	23
p38alpha-beta/CK2	0.042	0.078	-10000	0	-0.31	14	14
CEBPB	0.021	0.053	-10000	0	-0.28	10	10
SLC9A1	0.02	0.056	-10000	0	-0.28	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.014	0.074	0.23	1	-0.24	28	29
p38alpha-beta/MNK1	0.053	0.077	-10000	0	-0.26	14	14
JUN	-0.023	0.1	-10000	0	-0.31	43	43
PPARGC1A	0.022	0.054	-10000	0	-0.28	12	12
USF1	0.018	0.058	-10000	0	-0.26	17	17
RAB5/GDP/GDI1	0.005	0.077	-10000	0	-0.19	30	30
NOS2	0.014	0.055	-10000	0	-0.28	14	14
DDIT3	0.016	0.061	-10000	0	-0.22	25	25
RAB5A	0.041	0.006	-10000	0	0	13	13
HSPB1	0.002	0.05	0.28	2	-0.23	16	18
p38alpha-beta/HBP1	0.045	0.084	-10000	0	-0.21	25	25
CREB1	-0.005	0.098	-10000	0	-0.3	19	19
RAB5/GDP	0.03	0.012	-10000	0	-0.13	3	3
EIF4E	-0.007	0.064	0.19	22	-0.3	9	31
RPS6KA4	0.02	0.056	-10000	0	-0.28	14	14
PLA2G4A	-0.01	0.06	0.2	11	-0.31	11	22
GDI1	0.017	0.062	-10000	0	-0.25	22	22
TP53	0.002	0.064	0.2	1	-0.36	12	13
RPS6KA5	0.018	0.059	-10000	0	-0.25	19	19
ESR1	0.007	0.075	-10000	0	-0.22	44	44
HBP1	0.038	0.012	-10000	0	0	50	50
MEF2C	0.015	0.068	-10000	0	-0.28	21	21
MEF2A	0.017	0.058	-10000	0	-0.25	18	18
EIF4EBP1	-0.001	0.092	-10000	0	-0.2	82	82
KRT19	0.007	0.08	-10000	0	-0.22	47	47
ELK4	0.019	0.057	-10000	0	-0.27	15	15
ATF6	0.018	0.056	-10000	0	-0.26	16	16
ATF1	-0.005	0.098	-10000	0	-0.2	95	95
p38alpha-beta/MAPKAPK2	0.053	0.077	-10000	0	-0.24	16	16
p38alpha-beta/MAPKAPK3	0.055	0.076	-10000	0	-0.25	14	14

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.034	0.054	-10000	0	-0.4	5	5
VEGFR1 homodimer/NRP1	0.008	0.046	-10000	0	-0.4	5	5
mol:DAG	-0.024	0.039	0.19	1	-0.31	6	7
VEGFR1 homodimer/NRP1/VEGFR 121	0.007	0.042	-10000	0	-0.36	5	5
CaM/Ca2+	0.025	0.053	0.2	1	-0.28	7	8
HIF1A	0.045	0.033	-10000	0	-0.28	5	5
GAB1	0.038	0.012	-10000	0	0	52	52
AKT1	0.001	0.09	0.22	7	-0.27	16	23
PLCG1	-0.024	0.04	0.2	1	-0.31	6	7
NOS3	0.026	0.071	0.3	4	-0.27	9	13
CBL	0.04	0.008	-10000	0	0	23	23
mol:NO	0.028	0.072	0.27	6	-0.26	9	15
FLT1	0.019	0.044	-10000	0	-0.49	4	4
PGF	0.04	0.009	-10000	0	0	27	27
VEGFR1 homodimer/NRP2/VEGFR121	0.018	0.062	-10000	0	-0.31	8	8
CALM1	0.04	0.01	-10000	0	0	31	31
PIK3CA	0.03	0.019	-10000	0	0	155	155
eNOS/Hsp90	0.021	0.069	0.28	4	-0.25	9	13
endothelial cell proliferation	-0.003	0.066	0.24	4	-0.29	11	15
mol:Ca2+	-0.023	0.039	0.19	1	-0.31	6	7
MAPK3	-0.027	0.056	0.16	17	-0.25	9	26
MAPK1	-0.026	0.054	0.16	14	-0.25	9	23
PIK3R1	0.034	0.017	-10000	0	0	108	108
PLGF homodimer	0.04	0.009	-10000	0	0	27	27
PRKACA	0.035	0.015	-10000	0	0	89	89
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.036	0.015	-10000	0	0	80	80
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.008	0.046	-10000	0	-0.4	5	5
platelet activating factor biosynthetic process	-0.027	0.058	0.15	24	-0.3	5	29
PI3K	0.039	0.08	-10000	0	-0.24	16	16
PRKCA	-0.021	0.046	0.22	4	-0.27	8	12
PRKCB	-0.022	0.036	0.18	1	-0.29	6	7
VEGFR1 homodimer/PLGF homodimer	0.035	0.054	-10000	0	-0.4	5	5
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.039	0.011	-10000	0	0	42	42
mol:IP3	-0.024	0.039	0.19	1	-0.31	6	7
RASA1	-0.021	0.045	0.2	2	-0.34	6	8
NRP2	0.035	0.016	-10000	0	0	94	94
VEGFR1 homodimer	0.019	0.044	-10000	0	-0.49	4	4
VEGFB homodimer	0.039	0.011	-10000	0	0	42	42
NCK1	0.036	0.015	-10000	0	0	80	80
eNOS/Caveolin-1	0.043	0.082	0.3	4	-0.26	10	14
PTPN11	0.04	0.009	-10000	0	0	27	27
mol:PI-3-4-5-P3	0.037	0.079	-10000	0	-0.24	16	16
mol:L-citrulline	0.028	0.072	0.27	6	-0.26	9	15
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.066	-10000	0	-0.27	10	10
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.024	0.058	-10000	0	-0.28	10	10
CD2AP	0.037	0.014	-10000	0	0	67	67
PI3K/GAB1	0.044	0.088	-10000	0	-0.24	17	17
PDPK1	0.001	0.091	0.22	8	-0.31	7	15
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.028	0.056	-10000	0	-0.28	10	10
mol:NADP	0.028	0.072	0.27	6	-0.26	9	15
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.04	0.065	-10000	0	-0.26	10	10
VEGFR1 homodimer/NRP2	0.028	0.058	-10000	0	-0.34	8	8

×

Arf1 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
coatomer protein complex	0.022	0.047	0.15	65	-0.12	1	66
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.013	0.031	0.12	1	-0.14	4	5
AP2	0.038	0.045	-10000	0	-0.14	22	22
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.052	0.019	-10000	0	-0.12	1	1
CLTB	0.04	0.009	-10000	0	0	27	27
coatomer protein complex/ARF1/GTP/ER cargo protein	0.019	0.03	-10000	0	-0.15	14	14
CD4	0.032	0.018	-10000	0	0	132	132
CLTA	0.04	0.008	-10000	0	0	20	20
mol:GTP	-0.003	0.003	0.012	6	-0.02	1	7
ARFGAP1	-0.009	0.004	0	77	-10000	0	77
mol:PI-4-5-P2	0.01	0.016	0.079	25	-10000	0	25
ARF1/GTP	0.023	0.012	0.079	1	-0.14	1	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.025	0.055	0.17	59	-0.17	4	63
mol:Choline	0.01	0.016	0.079	25	-10000	0	25
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.039	0.012	-10000	0	0	50	50
DDEF1	0.005	0.012	0.08	12	-10000	0	12
ARF1/GDP	0.006	0.011	0.06	1	-0.07	5	6
AP2M1	0.032	0.018	-10000	0	0	137	137
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.01	0.016	0.05	16	-0.1	2	18
Rac/GTP	0.029	0.011	-10000	0	-0.13	1	1
ARF1/GTP/GGA3/ARF-GAP1	0.044	0.026	-10000	0	-0.1	1	1
ARFIP2	0.035	0.019	-10000	0	-0.041	28	28
COPA	0.04	0.009	-10000	0	0	29	29
RAC1	0.039	0.01	-10000	0	0	34	34
ARF1/GTP/coatomer protein complex	0.013	0.04	0.13	2	-0.16	19	21
ARF1/GTP/ARHGAP10	0.024	0.01	-10000	0	-0.11	1	1
GGA3	0.041	0.008	-10000	0	0	19	19
ARF1/GTP/Membrin	0.023	0.05	-10000	0	-0.22	21	21
AP2A1	0.039	0.011	-10000	0	0	43	43
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.011	0.033	-10000	0	-0.16	14	14
ARF1/GDP/Membrin	0.025	0.057	-10000	0	-0.25	21	21
Arfaptin 2/Rac/GDP	0.051	0.019	-10000	0	-0.11	1	1
CYTH2	-0.003	0.003	0.012	6	-0.02	1	7
ARF1/GTP/GGA3	0.049	0.021	-10000	0	-0.12	2	2
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.029	0.01	-10000	0	-0.13	1	1
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	0.008	0.055	-10000	0	-0.34	6	6
PLD2	0.01	0.016	0.08	25	-10000	0	25
ARF-GAP1/v-SNARE	-0.009	0.004	0	77	-10000	0	77
PIP5K1A	0.01	0.016	0.079	25	-10000	0	25
ARF1/GTP/Membrin/GBF1/p115	0.018	0.025	-10000	0	-0.075	17	17
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.01	0.016	0.079	25	-10000	0	25
KDEL Receptor/Ligand/ARF-GAP1	-0.009	0.004	0	77	-10000	0	77
GOSR2	0.011	0.052	-10000	0	-0.31	14	14
USO1	0.004	0.008	0.041	25	-0.029	1	26
GBF1	0.005	0.07	-10000	0	-0.34	22	22
ARF1/GTP/Arfaptin 2	0.05	0.02	-10000	0	-0.12	1	1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.038	0.061	-10000	0	-0.13	38	38

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.038	0.013	-10000	0	0	56	56
Ran/GTP/Exportin 1/HDAC4	-0.029	0.033	-10000	0	-0.16	24	24
MDM2/SUMO1	0.039	0.062	-10000	0	-0.18	18	18
HDAC4	0.041	0.007	-10000	0	0	15	15
Ran/GTP/Exportin 1/HDAC1	-0.031	0.04	-10000	0	-0.17	30	30
SUMO1	0.041	0.006	-10000	0	0	13	13
NPC/RanGAP1/SUMO1	0.008	0.033	-10000	0	-0.14	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.001	0.039	-10000	0	-0.17	15	15
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	13	13
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.04	0.009	-10000	0	0	30	30
SUMO1/HDAC4	0.041	0.062	-10000	0	-0.18	18	18
SUMO1/HDAC1	0.037	0.065	-10000	0	-0.18	25	25
RANGAP1	0.038	0.013	-10000	0	0	57	57
MDM2/SUMO1/SUMO1	0.083	0.056	-10000	0	-0.12	20	20
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.009	0.035	-10000	0	-0.15	25	25
Ran/GTP	0.023	0.058	0.17	1	-0.15	36	37
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.039	0.01	-10000	0	0	35	35
UBE2I	0.04	0.009	-10000	0	0	27	27
Ran/GTP/Exportin 1	0.019	0.068	0.2	13	-0.2	26	39
NPC	0.02	0.022	-10000	0	-0.085	23	23
PIAS2	0.038	0.012	-10000	0	0	51	51
PIAS1	0.04	0.009	-10000	0	0	28	28
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.038	0.017	-10000	0	-0.13	3	3
PDGFRB	0.037	0.014	-10000	0	0	64	64
SPHK1	0.014	0.073	-10000	0	-0.61	7	7
mol:S1P	0.013	0.067	-10000	0	-0.51	7	7
S1P1/S1P/Gi	0.022	0.09	-10000	0	-0.32	23	23
GNAO1	0.034	0.018	-10000	0	-0.002	108	108
PDGFB-D/PDGFRB/PLCgamma1	0.011	0.11	0.26	4	-0.29	32	36
PLCG1	0.006	0.097	0.21	12	-0.3	29	41
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.037	0.014	-10000	0	0	64	64
GNAI2	0.041	0.012	-10000	0	-0.013	24	24
GNAI3	0.039	0.015	-10000	0	-0.005	53	53
GNAI1	0.035	0.018	-10000	0	-0.002	102	102
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.026	0.024	0.2	6	-0.12	3	9
S1P1/S1P	0.023	0.061	-10000	0	-0.32	8	8
negative regulation of cAMP metabolic process	0.022	0.089	-10000	0	-0.32	23	23
MAPK3	0.009	0.1	-10000	0	-0.43	18	18
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
RhoA/GDP	0.03	0.012	-10000	0	-0.13	3	3
KDR	0.044	0.011	-10000	0	-10000	0	0
PLCB2	0.017	0.059	-10000	0	-0.29	8	8
RAC1	0.039	0.01	-10000	0	0	34	34
RhoA/GTP	0.024	0.056	-10000	0	-0.27	9	9
receptor internalization	0.021	0.058	-10000	0	-0.3	8	8
PTGS2	-0.001	0.15	-10000	0	-0.75	13	13
Rac1/GTP	0.022	0.055	-10000	0	-0.28	8	8
RHOA	0.041	0.007	-10000	0	0	14	14
VEGFA	0.004	0.002	-10000	0	-10000	0	0
negative regulation of T cell proliferation	0.022	0.089	-10000	0	-0.32	23	23
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.039	0.015	-10000	0	-0.006	51	51
MAPK1	0.01	0.11	-10000	0	-0.49	15	15
S1P1/S1P/PDGFB-D/PDGFRB	0.034	0.072	-10000	0	-0.26	9	9
ABCC1	0.041	0.009	-10000	0	0	26	26

×

Effects of Botulinum toxin

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
STX1A	-0.01	0.002	0	13	-10000	0	13
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.057	0.019	-10000	0	-0.14	2	2
STXBP1	0.039	0.011	-10000	0	0	41	41
ACh/CHRNA1	0.029	0.025	0.092	2	-0.049	36	38
RAB3GAP2/RIMS1/UNC13B	0.071	0.04	-10000	0	-0.12	14	14
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	0.041	0.007	-10000	0	0	15	15
mol:ACh	0.004	0.025	0.073	35	-0.085	5	40
RAB3GAP2	0.039	0.01	-10000	0	0	37	37
STX1A/SNAP25/VAMP2	0.056	0.058	0.18	2	-0.13	5	7
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.029	0.025	0.092	2	-0.049	36	38
UNC13B	0.04	0.009	-10000	0	0	25	25
CHRNA1	0.038	0.013	-10000	0	0	59	59
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.03	0.026	0.092	2	-0.049	37	39
SNAP25	0.006	0.002	-10000	0	0	71	71
VAMP2	0.005	0.002	-10000	0	0	67	67
SYT1	0.038	0.012	-10000	0	0	47	47
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.034	0.011	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.056	0.058	0.18	2	-0.13	5	7

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.063	0.035	-9999	0	-0.098	17	17
MAPK9	0.009	0.002	-9999	0	0	39	39
adrenocorticotropin secretion	-0.01	0.003	0	44	-10000	0	44
GNB1/GNG2	0.049	0.032	-9999	0	-0.11	19	19
GNB1	0.041	0.005	-9999	0	0	7	7
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-10000	0	0
mol:GDP	0	0	-9999	0	-10000	0	0
MAPK14	0.009	0.002	-9999	0	0	28	28
Gs family/GTP	0.026	0.006	-9999	0	-10000	0	0
EntrezGene:2778	0	0	-9999	0	-10000	0	0
vasopressin secretion	0	0	-9999	0	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-10000	0	0
glutamate secretion	0.002	0	-9999	0	-10000	0	0
GNAL	0.04	0.009	-9999	0	0	26	26
GNG2	0.039	0.01	-9999	0	0	34	34
CRH	0.039	0.011	-9999	0	0	44	44
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.009	0.002	-9999	0	0	30	30
MAPK11	0.007	0.004	-9999	0	0	142	142

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.047	0.012	-10000	0	-0.072	4	4
NFATC2	0.048	0.18	0.41	5	-0.39	35	40
NFATC3	0.069	0.067	0.29	26	-0.26	2	28
CD40LG	0.083	0.15	0.49	5	-0.5	2	7
ITCH	0.021	0.057	0.2	6	-0.23	20	26
CBLB	0.019	0.061	0.2	6	-0.25	22	28
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.047	0.14	0.38	2	-0.52	7	9
JUNB	0.03	0.019	-10000	0	0	160	160
CaM/Ca2+/Calcineurin A alpha-beta B1	0.043	0.051	-10000	0	-0.18	24	24
T cell anergy	0.002	0.071	0.27	6	-0.29	20	26
TLE4	0.01	0.16	0.28	4	-0.41	47	51
Jun/NFAT1-c-4/p21SNFT	0.082	0.15	-10000	0	-0.48	1	1
AP-1/NFAT1-c-4	0.092	0.19	-10000	0	-0.56	1	1
IKZF1	0.023	0.11	0.22	19	-0.26	35	54
T-helper 2 cell differentiation	0.035	0.14	0.45	2	-0.49	1	3
AP-1/NFAT1	0.038	0.14	0.32	2	-0.27	28	30
CALM1	0.042	0.036	-10000	0	-0.12	21	21
EGR2	0.06	0.16	0.57	8	-1	2	10
EGR3	0.053	0.14	0.57	6	-0.53	1	7
NFAT1/FOXP3	0.059	0.14	0.33	3	-0.28	32	35
EGR1	0.028	0.021	-10000	0	-0.035	2	2
JUN	0.04	0.026	0.14	2	-0.045	10	12
EGR4	0.041	0.009	-10000	0	-0.035	2	2
mol:Ca2+	0.005	0.022	-10000	0	-0.1	23	23
GBP3	-0.019	0.21	0.3	9	-0.46	91	100
FOSL1	0.041	0.007	-10000	0	0	15	15
NFAT1-c-4/MAF/IRF4	0.095	0.15	-10000	0	-0.47	2	2
DGKA	0.026	0.12	0.3	7	-0.31	30	37
CREM	0.04	0.008	-10000	0	-0.002	21	21
NFAT1-c-4/PPARG	0.084	0.14	-10000	0	-0.5	2	2
CTLA4	0.027	0.1	0.23	1	-0.24	31	32
NFAT1-c-4 (dimer)/EGR1	0.062	0.15	-10000	0	-0.54	2	2
NFAT1-c-4 (dimer)/EGR4	0.091	0.15	-10000	0	-0.5	2	2
FOS	0.029	0.029	0.14	2	-0.042	8	10
IFNG	0.036	0.13	-10000	0	-0.49	6	6
T cell activation	0.054	0.12	0.6	1	-10000	0	1
MAF	0.036	0.015	-10000	0	0	84	84
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.06	0.13	0.57	3	-0.51	22	25
TNF	0.047	0.13	0.46	2	-0.52	2	4
FASLG	0.05	0.17	0.7	1	-1	3	4
TBX21	0.047	0.013	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.037	0.018	-10000	0	-0.12	1	1
PTPN1	0.027	0.12	0.32	3	-0.29	28	31
NFAT1-c-4/ICER1	0.085	0.14	-10000	0	-0.5	2	2
GATA3	0.042	0.011	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.039	0.13	-10000	0	-0.48	6	6
IL2RA	0.05	0.15	0.39	1	-0.47	9	10
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.022	0.12	0.27	2	-0.32	28	30
E2F1	0.032	0.05	-10000	0	-0.18	27	27
PPARG	0.039	0.01	-10000	0	0	37	37
SLC3A2	0.025	0.13	0.29	5	-0.32	30	35
IRF4	0.041	0.008	-10000	0	0	19	19
PTGS2	0.056	0.14	0.68	1	-0.51	3	4
CSF2	0.078	0.15	0.49	5	-0.5	2	7
JunB/Fra1/NFAT1-c-4	0.077	0.15	-10000	0	-0.48	2	2
IL4	0.034	0.14	0.45	2	-0.51	1	3
IL5	0.078	0.15	0.48	4	-0.5	2	6
IL2	0.054	0.12	0.6	1	-10000	0	1
IL3	0.037	0.079	-10000	0	-0.42	10	10
RNF128	0.023	0.045	0.2	7	-0.16	22	29
NFATC1	0.06	0.13	0.52	21	-0.57	3	24
CDK4	-0.078	0.28	-10000	0	-1.2	28	28
PTPRK	0.013	0.15	0.28	5	-0.39	45	50
IL8	0.048	0.14	0.55	4	-0.49	2	6
POU2F1	0.046	0.01	-10000	0	-10000	0	0

×

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

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
MAP4K1	0.01	0.068	0.27	6	-0.4	2	8
CRKL	0.014	0.065	0.29	3	-0.42	2	5
HRAS	0.029	0.081	0.25	1	-0.28	9	10
mol:PIP3	0.023	0.089	0.36	1	-0.33	9	10
SPRED1	0.035	0.015	-10000	0	0	90	90
SPRED2	0.04	0.009	-10000	0	0	24	24
GAB1	0.018	0.061	0.22	1	-0.44	2	3
FOXO3	0.021	0.091	0.35	1	-0.38	11	12
AKT1	0.022	0.096	0.37	1	-0.41	11	12
BAD	0.017	0.092	0.35	1	-0.38	11	12
megakaryocyte differentiation	0.023	0.059	0.24	3	-0.3	1	4
GSK3B	0.021	0.098	0.32	8	-0.38	11	19
RAF1	0.021	0.076	0.26	6	-0.25	8	14
SHC1	0.04	0.01	-10000	0	0	31	31
STAT3	0.018	0.061	0.26	3	-0.44	2	5
STAT1	0.032	0.11	-10000	0	-0.87	3	3
HRAS/SPRED1	0.033	0.083	0.26	3	-0.29	5	8
cell proliferation	0.018	0.062	0.24	3	-0.43	2	5
PIK3CA	0.03	0.019	-10000	0	0	155	155
TEC	0.033	0.017	-10000	0	0	115	115
RPS6KB1	0.021	0.099	0.3	1	-0.38	11	12
HRAS/SPRED2	0.04	0.084	0.26	3	-0.27	6	9
LYN/TEC/p62DOK	0.041	0.097	-10000	0	-0.34	4	4
MAPK3	0.016	0.065	0.22	7	-0.24	5	12
STAP1	0.023	0.061	0.24	3	-0.43	2	5
GRAP2	0.038	0.013	-10000	0	0	57	57
JAK2	0.029	0.11	-10000	0	-0.66	4	4
STAT1 (dimer)	0.031	0.12	-10000	0	-0.85	3	3
mol:Gleevec	-0.002	0.003	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.062	0.092	0.3	1	-0.34	4	5
actin filament polymerization	0.024	0.061	0.25	2	-0.42	2	4
LYN	0.036	0.015	-10000	0	0	83	83
STAP1/STAT5A (dimer)	0.017	0.099	0.3	1	-0.5	5	6
PIK3R1	0.034	0.017	-10000	0	0	108	108
CBL/CRKL/GRB2	0.044	0.083	0.42	1	-0.43	2	3
PI3K	0.023	0.1	0.32	1	-0.35	12	13
PTEN	0.039	0.011	-10000	0	0	38	38
SCF/KIT/EPO/EPOR	0.061	0.14	-10000	0	-1.3	2	2
MAPK8	0.018	0.063	0.24	3	-0.44	2	5
STAT3 (dimer)	0.02	0.063	0.25	4	-0.43	2	6
positive regulation of transcription	0.016	0.058	0.2	8	-0.2	5	13
mol:GDP	0.036	0.086	0.27	1	-0.29	6	7
PIK3C2B	0.019	0.066	0.25	4	-0.44	2	6
CBL/CRKL	0.03	0.077	0.42	1	-0.44	2	3
FER	0.018	0.061	0.24	2	-0.44	2	4
SH2B3	0.023	0.061	0.24	3	-0.43	2	5
PDPK1	0.022	0.087	0.29	4	-0.3	8	12
SNAI2	0.023	0.068	0.25	4	-0.51	2	6
positive regulation of cell proliferation	0.02	0.11	-10000	0	-0.7	3	3
KITLG	0.044	0.015	-10000	0	-0.041	3	3
cell motility	0.02	0.11	-10000	0	-0.7	3	3
PTPN6	0.033	0.017	-10000	0	-0.005	80	80
EPOR	0.01	0.17	-10000	0	-0.57	27	27
STAT5A (dimer)	0.021	0.1	0.31	1	-0.51	5	6
SOCS1	0.038	0.012	-10000	0	0	50	50
cell migration	-0.017	0.06	0.43	2	-0.26	1	3
SOS1	0.038	0.013	-10000	0	0	56	56
EPO	0.043	0.011	-10000	0	-0.035	3	3
VAV1	0.037	0.014	-10000	0	0	68	68
GRB10	0.018	0.063	0.26	1	-0.44	2	3
PTPN11	0.038	0.011	-10000	0	-0.004	31	31
SCF/KIT	0.027	0.065	0.25	3	-0.45	2	5
GO:0007205	-0.002	0.004	-10000	0	-10000	0	0
MAP2K1	0.014	0.067	0.22	11	-0.24	3	14
CBL	0.04	0.008	-10000	0	0	23	23
KIT	0.017	0.16	-10000	0	-0.63	10	10
MAP2K2	0.013	0.063	0.22	6	-0.23	4	10
SHC/Grb2/SOS1	0.065	0.094	0.3	1	-0.33	4	5
STAT5A	0.023	0.1	-10000	0	-0.53	5	5
GRB2	0.041	0.007	-10000	0	0	17	17
response to radiation	0.027	0.071	0.26	6	-0.5	2	8
SHC/GRAP2	0.053	0.024	-10000	0	-0.14	1	1
PTPRO	0.02	0.056	0.24	3	-0.3	1	4
SH2B2	0.023	0.061	0.24	3	-0.43	2	5
DOK1	0.04	0.009	-10000	0	0	24	24
MATK	0.018	0.06	0.26	1	-0.44	2	3
CREBBP	0.059	0.029	0.15	2	-0.15	3	5
BCL2	-0.021	0.23	-10000	0	-0.66	34	34

×

Aurora C 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.042	0.004	-9999	0	5	5
Aurora C/Aurora B/INCENP	0.063	0.046	-9999	-0.11	28	28
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.005	0.065	-9999	-0.39	14	14
AURKB	0.036	0.015	-9999	0	81	81
AURKC	0.042	0.002	-9999	0	1	1

×

Glypican 2 network

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
MDK	0.04	0.009	-9999	0	24	24
GPC2	0.04	0.008	-9999	0	22	22
GPC2/Midkine	0.055	0.032	-9999	-0.14	13	13
neuron projection morphogenesis	0.054	0.032	-9999	-0.14	13	13

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.039	0.01	-10000	0	0	33	33
CLTC	0.015	0.089	0.23	1	-0.48	11	12
calcium ion-dependent exocytosis	0.017	0.045	0.18	2	-0.19	6	8
Dynamin 2/GTP	0.021	0.042	-10000	0	-0.11	45	45
EXOC4	0.038	0.012	-10000	0	0	49	49
CD59	0.01	0.062	-10000	0	-0.36	11	11
CPE	0.012	0.013	-10000	0	-0.11	4	4
CTNNB1	0.04	0.01	-10000	0	0	31	31
membrane fusion	0.004	0.035	-10000	0	-0.2	5	5
CTNND1	-0.006	0.072	0.18	57	-0.2	3	60
DNM2	0.037	0.014	-10000	0	0	72	72
mol:PI-4-5-P2	0.017	0.056	0.2	3	-0.24	12	15
TSHR	0.014	0.015	-10000	0	-0.11	7	7
INS	0.006	0.1	-10000	0	-0.44	26	26
BIN1	0.041	0.007	-10000	0	0	18	18
mol:Choline	0.004	0.035	-10000	0	-0.2	5	5
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.014	-10000	0	-0.11	5	5
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.041	0.008	-10000	0	0	19	19
mol:Ca2+	0.021	0.042	-10000	0	-0.11	45	45
JUP	0.008	0.064	-10000	0	-0.36	11	11
ASAP2/amphiphysin II	0.048	0.024	-10000	0	-0.098	11	11
ARF6/GTP	0.028	0.019	-10000	0	-0.13	8	8
CDH1	0.007	0.064	-10000	0	-0.38	10	10
clathrin-independent pinocytosis	0.028	0.019	-10000	0	-0.13	8	8
MAPK8IP3	0.04	0.009	-10000	0	0	27	27
positive regulation of endocytosis	0.028	0.019	-10000	0	-0.13	8	8
EXOC2	0.041	0.006	-10000	0	0	13	13
substrate adhesion-dependent cell spreading	0.009	0.1	-10000	0	-0.36	27	27
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.039	0.011	-10000	0	0	42	42
regulation of calcium-dependent cell-cell adhesion	-0.035	0.086	0.35	12	-10000	0	12
positive regulation of phagocytosis	0.015	0.015	-10000	0	-0.11	7	7
ARF6/GTP/JIP3	0.05	0.024	-10000	0	-0.11	8	8
ACAP1	0.005	0.034	-10000	0	-0.18	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.013	0.061	-10000	0	-0.34	11	11
clathrin heavy chain/ACAP1	0.015	0.078	0.26	2	-0.38	11	13
JIP4/KLC1	0.045	0.03	-10000	0	-0.098	18	18
EXOC1	0.038	0.012	-10000	0	0	47	47
exocyst	0.008	0.1	-10000	0	-0.37	27	27
RALA/GTP	0.027	0.021	-10000	0	-0.13	9	9
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.047	0.032	-10000	0	-0.11	18	18
receptor recycling	0.028	0.019	-10000	0	-0.13	8	8
CTNNA1	-0.006	0.071	0.18	55	-0.2	3	58
NME1	0.014	0.014	-10000	0	-0.11	5	5
clathrin coat assembly	0.015	0.089	0.23	1	-0.47	11	12
IL2RA	0.013	0.061	0.22	1	-0.35	10	11
VAMP3	0.015	0.015	-10000	0	-0.11	7	7
GLUT4/clathrin heavy chain/ACAP1	0.038	0.081	-10000	0	-0.35	11	11
EXOC6	0.038	0.012	-10000	0	0	55	55
PLD1	0	0.05	-10000	0	-0.2	29	29
PLD2	0.014	0.029	-10000	0	-0.19	5	5
EXOC5	0.04	0.009	-10000	0	0	27	27
PIP5K1C	0.012	0.05	0.18	2	-0.24	10	12
SDC1	0.01	0.061	-10000	0	-0.36	10	10
ARF6/GDP	0.025	0.04	-10000	0	-0.12	38	38
EXOC7	0.041	0.006	-10000	0	0	12	12
E-cadherin/beta catenin	0.038	0.089	-10000	0	-0.36	12	12
mol:Phosphatidic acid	0.004	0.035	-10000	0	-0.2	5	5
endocytosis	-0.047	0.023	0.098	11	-10000	0	11
SCAMP2	0.04	0.008	-10000	0	0	23	23
ADRB2	0.008	0.087	-10000	0	-0.43	12	12
EXOC3	0.041	0.005	-10000	0	0	8	8
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.026	0.046	0.19	5	-0.11	45	50
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.008	0.086	-10000	0	-0.43	12	12
RALA	0.04	0.009	-10000	0	0	30	30
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.021	0.091	-10000	0	-0.4	11	11

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.062	0.028	-10000	0	-0.098	1	1
RGS9BP	0.037	0.013	-10000	0	0	62	62
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.05	0.017	-10000	0	-10000	0	0
mol:ADP	-0.01	0.003	-10000	0	-10000	0	0
GNAT2	0.041	0.005	-10000	0	0	8	8
RGS9-1/Gbeta5/R9AP	0.067	0.035	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.05	0.018	-10000	0	-10000	0	0
GRK7	0.038	0.012	-10000	0	0	51	51
CNGB3	0.038	0.012	-10000	0	0	53	53
Cone Metarhodopsin II/X-Arrestin	0.031	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.003	0.057	0.19	43	-10000	0	43
Cone PDE6	0.088	0.057	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0.024	0.008	-10000	0	-10000	0	0
Na + (4 Units)	0.066	0.03	-10000	0	-10000	0	0
GNAT2/GDP	0.08	0.039	-10000	0	-0.1	1	1
GNB5	0.04	0.009	-10000	0	0	29	29
mol:GMP (4 units)	-0.002	0.06	0.19	49	-10000	0	49
Cone Transducin	0.067	0.031	-10000	0	-0.11	1	1
SLC24A2	0.039	0.011	-10000	0	0	41	41
GNB3/GNGT2	0.052	0.024	-10000	0	-0.14	1	1
GNB3	0.037	0.014	-10000	0	0	66	66
GNAT2/GTP	0.031	0.004	-10000	0	-10000	0	0
CNGA3	0.041	0.005	-10000	0	0	7	7
ARR3	0.042	0.002	-10000	0	0	1	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.051	0.018	-10000	0	-10000	0	0
mol:Pi	0.066	0.035	-10000	0	-0.12	1	1
Cone CNG Channel	0.079	0.046	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.039	0.011	-10000	0	0	41	41
RGS9	0.039	0.011	-10000	0	0	39	39
PDE6C	0.04	0.009	-10000	0	0	24	24
GNGT2	0.04	0.009	-10000	0	0	25	25
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.038	0.013	-10000	0	0	59	59

×

Visual signal transduction: Rods

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.04	0.008	-10000	0	0	20	20
GNAT1/GTP	0.03	0.005	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.053	0.013	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.049	0.021	-10000	0	-0.11	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.041	0.007	-10000	0	0	15	15
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.069	0.037	-10000	0	-0.11	2	2
mol:Na +	0.07	0.042	-10000	0	-0.11	1	1
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.067	0.035	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.086	0.05	-10000	0	-0.11	1	1
CNGB1	0.038	0.012	-10000	0	0	49	49
RDH5	0.037	0.014	-10000	0	0	72	72
SAG	0.041	0.006	-10000	0	0	10	10
mol:Ca2+	-0.018	0.082	0.33	21	-10000	0	21
Na + (4 Units)	0.056	0.038	-10000	0	-0.11	1	1
RGS9	0.039	0.011	-10000	0	0	39	39
GNB1/GNGT1	0.057	0.023	-10000	0	-0.14	5	5
GNAT1/GDP	0.079	0.039	-10000	0	-0.1	1	1
GUCY2D	0.039	0.01	-10000	0	0	37	37
GNGT1	0.04	0.009	-10000	0	0	29	29
GUCY2F	0.042	0.002	-10000	0	0	1	1
GNB5	0.04	0.009	-10000	0	0	29	29
mol:GMP (4 units)	0.04	0.025	0.17	13	-0.1	2	15
mol:11-cis-retinal	0.037	0.014	-10000	0	0	72	72
mol:cGMP	0.077	0.034	0.2	2	-0.11	1	3
GNB1	0.041	0.005	-10000	0	0	7	7
Rhodopsin	0.05	0.031	-10000	0	-0.14	7	7
SLC24A1	0.04	0.008	-10000	0	0	20	20
CNGA1	0.041	0.008	-10000	0	0	19	19
Metarhodopsin II	0.026	0.005	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.093	0.038	-10000	0	-0.11	1	1
RGS9BP	0.037	0.013	-10000	0	0	62	62
Metarhodopsin II/Transducin	0.025	0.019	-10000	0	-0.14	6	6
GCAP Family/Ca ++	0.073	0.024	-10000	0	-0.11	1	1
PDE6A/B	0.059	0.013	-10000	0	-10000	0	0
mol:Pi	0.066	0.035	-10000	0	-0.12	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.073	0.027	-10000	0	-0.11	5	5
PDE6B	0.041	0.005	-10000	0	0	7	7
PDE6A	0.041	0.008	-10000	0	0	19	19
PDE6G	0.038	0.013	-10000	0	0	58	58
RHO	0.04	0.008	-10000	0	0	23	23
PDE6	0.096	0.054	-10000	0	-0.15	2	2
GUCA1A	0.04	0.009	-10000	0	0	25	25
GC2/GCAP Family	0.098	0.031	-10000	0	-0.11	1	1
GUCA1C	0.04	0.009	-10000	0	0	28	28
GUCA1B	0.04	0.008	-10000	0	0	23	23