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

Pathway.Name	Avg.Num.Perturbations
PLK2 and PLK4 events	186
FOXM1 transcription factor network	133
TCGA08_p53	100
HIF-1-alpha transcription factor network	97
Wnt signaling	96
Ephrin B reverse signaling	93
Endothelins	91
LPA receptor mediated events	90
Osteopontin-mediated events	89
Syndecan-1-mediated signaling events	86

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	186	559	3	-0.011	0.036	1000	-1000	-0.017	-1000
FOXM1 transcription factor network	133	6823	51	-0.51	0.038	1000	-1000	-0.024	-1000
TCGA08_p53	100	705	7	-0.062	0.038	1000	-1000	-0.009	-1000
HIF-1-alpha transcription factor network	97	7428	76	-0.048	0.093	1000	-1000	0	-1000
Wnt signaling	96	676	7	-0.019	0.041	1000	-1000	0.004	-1000
Ephrin B reverse signaling	93	4510	48	-0.2	0.08	1000	-1000	-0.05	-1000
Endothelins	91	8759	96	-0.18	0.044	1000	-1000	-0.017	-1000
LPA receptor mediated events	90	9234	102	-0.047	0.041	1000	-1000	-0.048	-1000
Osteopontin-mediated events	89	3382	38	-0.18	0.041	1000	-1000	-0.006	-1000
Syndecan-1-mediated signaling events	86	2948	34	-0.038	0.04	1000	-1000	-0.008	-1000
LPA4-mediated signaling events	83	1003	12	-0.015	0.058	1000	-1000	-0.014	-1000
amb2 Integrin signaling	83	6833	82	-0.082	0.081	1000	-1000	-0.014	-1000
Nectin adhesion pathway	81	5165	63	-0.083	0.062	1000	-1000	-0.007	-1000
TCGA08_retinoblastoma	81	653	8	-0.012	0.019	1000	-1000	-0.007	-1000
TRAIL signaling pathway	78	3781	48	-0.022	0.042	1000	-1000	-0.017	-1000
PDGFR-alpha signaling pathway	76	3382	44	-0.12	0.05	1000	-1000	-0.02	-1000
Nongenotropic Androgen signaling	76	3974	52	-0.12	0.062	1000	-1000	-0.016	-1000
BARD1 signaling events	74	4239	57	-0.038	0.064	1000	-1000	-0.069	-1000
Thromboxane A2 receptor signaling	73	7735	105	-0.15	0.072	1000	-1000	-0.024	-1000
TCGA08_rtk_signaling	72	1885	26	-0.016	0.04	1000	-1000	-0.02	-1000
Signaling events mediated by the Hedgehog family	71	3702	52	-0.065	0.058	1000	-1000	-0.024	-1000
Paxillin-dependent events mediated by a4b1	69	2519	36	-0.065	0.068	1000	-1000	-0.055	-1000
Syndecan-4-mediated signaling events	69	4646	67	-0.064	0.045	1000	-1000	-0.031	-1000
Ras signaling in the CD4+ TCR pathway	69	1179	17	-0.003	0.053	1000	-1000	-0.003	-1000
IL23-mediated signaling events	66	3968	60	-0.17	0.055	1000	-1000	-0.026	-1000
E-cadherin signaling in keratinocytes	66	2839	43	-0.028	0.049	1000	-1000	-0.01	-1000
Cellular roles of Anthrax toxin	65	2537	39	-0.081	0.04	1000	-1000	-0.015	-1000
Signaling events mediated by PTP1B	65	4978	76	-0.059	0.069	1000	-1000	-0.022	-1000
Integrins in angiogenesis	65	5517	84	-0.058	0.056	1000	-1000	-0.017	-1000
Signaling events mediated by PRL	65	2234	34	-0.018	0.04	1000	-1000	-0.025	-1000
Fc-epsilon receptor I signaling in mast cells	64	6301	97	-0.073	0.046	1000	-1000	-0.034	-1000
IL1-mediated signaling events	64	4000	62	-0.044	0.071	1000	-1000	-0.017	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	63	5373	85	-0.16	0.05	1000	-1000	-0.022	-1000
Canonical Wnt signaling pathway	62	3195	51	-0.18	0.097	1000	-1000	-0.022	-1000
IL6-mediated signaling events	62	4686	75	-0.14	0.049	1000	-1000	-0.035	-1000
Noncanonical Wnt signaling pathway	61	1593	26	-0.029	0.041	1000	-1000	-0.023	-1000
IL2 signaling events mediated by STAT5	61	1342	22	-0.042	0.047	1000	-1000	-0.004	-1000
IGF1 pathway	61	3507	57	-0.021	0.065	1000	-1000	-0.014	-1000
HIF-2-alpha transcription factor network	60	2599	43	-0.061	0.069	1000	-1000	-0.085	-1000
a4b1 and a4b7 Integrin signaling	59	297	5	0.032	0.039	1000	-1000	0.037	-1000
BMP receptor signaling	59	4838	81	-0.02	0.07	1000	-1000	-0.004	-1000
IL4-mediated signaling events	57	5211	91	-0.22	0.059	1000	-1000	-0.042	-1000
IFN-gamma pathway	57	3905	68	-0.05	0.061	1000	-1000	-0.028	-1000
FoxO family signaling	57	3648	64	-0.19	0.046	1000	-1000	-0.016	-1000
TCR signaling in naïve CD8+ T cells	57	5313	93	-0.076	0.081	1000	-1000	-0.021	-1000
FAS signaling pathway (CD95)	55	2614	47	-0.06	0.052	1000	-1000	-0.026	-1000
EPHB forward signaling	55	4683	85	-0.056	0.16	1000	-1000	-0.039	-1000
E-cadherin signaling in the nascent adherens junction	55	4180	76	-0.054	0.072	1000	-1000	-0.028	-1000
E-cadherin signaling events	55	279	5	0.035	0.048	1000	-1000	0.037	-1000
IL12-mediated signaling events	54	4730	87	-0.18	0.061	1000	-1000	-0.027	-1000
Paxillin-independent events mediated by a4b1 and a4b7	54	2034	37	-0.019	0.07	1000	-1000	-0.011	-1000
Retinoic acid receptors-mediated signaling	54	3150	58	-0.083	0.059	1000	-1000	-0.004	-1000
Syndecan-2-mediated signaling events	53	3688	69	0	0.063	1000	-1000	-0.009	-1000
Plasma membrane estrogen receptor signaling	51	4451	86	-0.089	0.085	1000	-1000	-0.019	-1000
Class I PI3K signaling events	50	3670	73	-0.015	0.05	1000	-1000	-0.015	-1000
BCR signaling pathway	50	4967	99	-0.077	0.07	1000	-1000	-0.032	-1000
Presenilin action in Notch and Wnt signaling	49	2989	61	-0.16	0.075	1000	-1000	-0.039	-1000
IL2 signaling events mediated by PI3K	49	2887	58	-0.062	0.041	1000	-1000	-0.016	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	49	2228	45	-0.057	0.075	1000	-1000	-0.015	-1000
ErbB4 signaling events	48	3332	69	-0.07	0.057	1000	-1000	-0.028	-1000
Caspase cascade in apoptosis	47	3516	74	-0.11	0.051	1000	-1000	-0.017	-1000
EPO signaling pathway	47	2615	55	0	0.073	1000	-1000	-0.014	-1000
Stabilization and expansion of the E-cadherin adherens junction	47	3528	74	-0.076	0.067	1000	-1000	-0.057	-1000
Circadian rhythm pathway	46	1017	22	-0.081	0.044	1000	-1000	-0.018	-1000
Arf6 signaling events	46	2873	62	0	0.081	1000	-1000	0	-1000
Aurora B signaling	45	3080	67	-0.057	0.066	1000	-1000	-0.025	-1000
Reelin signaling pathway	44	2464	56	-0.012	0.094	1000	-1000	-0.005	-1000
PLK1 signaling events	43	3708	85	-0.043	0.05	1000	-1000	-0.012	-1000
Regulation of Telomerase	43	4470	102	-0.11	0.071	1000	-1000	-0.016	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	43	1443	33	-0.006	0.085	1000	-1000	-0.009	-1000
Canonical NF-kappaB pathway	42	1676	39	-0.035	0.063	1000	-1000	-0.018	-1000
p75(NTR)-mediated signaling	41	5208	125	-0.058	0.098	1000	-1000	-0.035	-1000
Regulation of p38-alpha and p38-beta	41	2232	54	-0.028	0.09	1000	-1000	0	-1000
ErbB2/ErbB3 signaling events	40	2608	65	-0.034	0.048	1000	-1000	-0.038	-1000
RXR and RAR heterodimerization with other nuclear receptor	40	2103	52	-0.038	0.094	1000	-1000	-0.015	-1000
EGFR-dependent Endothelin signaling events	40	845	21	-0.016	0.081	1000	-1000	-0.01	-1000
Regulation of Androgen receptor activity	40	2863	70	-0.086	0.07	1000	-1000	-0.021	-1000
Neurotrophic factor-mediated Trk receptor signaling	38	4670	120	-0.049	0.091	1000	-1000	-0.022	-1000
PDGFR-beta signaling pathway	38	3737	97	-0.036	0.085	1000	-1000	-0.034	-1000
Insulin-mediated glucose transport	37	1185	32	-0.018	0.046	1000	-1000	-0.017	-1000
mTOR signaling pathway	37	1983	53	-0.049	0.056	1000	-1000	-0.017	-1000
p38 MAPK signaling pathway	37	1642	44	-0.044	0.072	1000	-1000	0	-1000
Signaling mediated by p38-gamma and p38-delta	36	546	15	-0.039	0.039	1000	-1000	-0.017	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	35	1918	54	-0.018	0.055	1000	-1000	-0.018	-1000
Aurora A signaling	35	2137	60	-0.043	0.066	1000	-1000	-0.017	-1000
Arf6 downstream pathway	35	1523	43	-0.034	0.061	1000	-1000	-0.046	-1000
Syndecan-3-mediated signaling events	35	1242	35	-0.013	0.072	1000	-1000	-0.01	-1000
ceramide signaling pathway	34	1676	49	-0.03	0.059	1000	-1000	-0.013	-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	763	23	-0.016	0.066	1000	-1000	-0.001	-1000
Ephrin A reverse signaling	33	232	7	-0.013	0.04	1000	-1000	-0.009	-1000
Hedgehog signaling events mediated by Gli proteins	33	2183	65	0	0.074	1000	-1000	-0.007	-1000
FOXA2 and FOXA3 transcription factor networks	33	1542	46	-0.13	0.056	1000	-1000	-0.014	-1000
Ceramide signaling pathway	33	2515	76	-0.019	0.081	1000	-1000	-0.017	-1000
S1P3 pathway	33	1395	42	-0.02	0.053	1000	-1000	-0.011	-1000
Regulation of nuclear SMAD2/3 signaling	32	4414	136	-0.091	0.1	1000	-1000	-0.051	-1000
JNK signaling in the CD4+ TCR pathway	32	547	17	-0.005	0.078	1000	-1000	0	-1000
Class I PI3K signaling events mediated by Akt	32	2212	68	-0.034	0.078	1000	-1000	-0.017	-1000
S1P5 pathway	32	546	17	-0.007	0.041	1000	-1000	-0.018	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	32	2667	83	-0.014	0.072	1000	-1000	-0.017	-1000
S1P4 pathway	32	804	25	-0.013	0.053	1000	-1000	-0.007	-1000
Signaling events mediated by HDAC Class I	31	3307	104	-0.041	0.074	1000	-1000	-0.04	-1000
Glypican 1 network	29	1407	48	-0.04	0.068	1000	-1000	-0.038	-1000
Signaling events regulated by Ret tyrosine kinase	29	2431	82	-0.008	0.091	1000	-1000	-0.018	-1000
Atypical NF-kappaB pathway	29	914	31	-0.016	0.041	1000	-1000	-0.017	-1000
Signaling events mediated by VEGFR1 and VEGFR2	29	3676	125	-0.022	0.072	1000	-1000	-0.027	-1000
Nephrin/Neph1 signaling in the kidney podocyte	28	956	34	-0.049	0.085	1000	-1000	-0.048	-1000
Sphingosine 1-phosphate (S1P) pathway	28	806	28	-0.019	0.053	1000	-1000	-0.017	-1000
Glucocorticoid receptor regulatory network	27	3182	114	-0.1	0.075	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	27	354	13	0	0.095	1000	-1000	0	-1000
Coregulation of Androgen receptor activity	26	2047	76	-0.011	0.052	1000	-1000	-0.018	-1000
Calcium signaling in the CD4+ TCR pathway	26	822	31	-0.042	0.084	1000	-1000	-0.019	-1000
IL27-mediated signaling events	26	1372	51	-0.009	0.079	1000	-1000	-0.031	-1000
VEGFR1 specific signals	26	1460	56	-0.03	0.045	1000	-1000	-0.017	-1000
Signaling events mediated by HDAC Class II	25	1891	75	-0.037	0.094	1000	-1000	-0.024	-1000
Insulin Pathway	25	1898	74	-0.027	0.1	1000	-1000	-0.029	-1000
Angiopoietin receptor Tie2-mediated signaling	25	2215	88	-0.045	0.074	1000	-1000	-0.048	-1000
Arf1 pathway	24	1298	54	-0.01	0.052	1000	-1000	-0.009	-1000
Signaling events mediated by HDAC Class III	23	955	40	-0.064	0.072	1000	-1000	-0.056	-1000
Sumoylation by RanBP2 regulates transcriptional repression	22	604	27	-0.031	0.083	1000	-1000	-0.024	-1000
S1P1 pathway	21	786	36	-0.002	0.043	1000	-1000	-0.011	-1000
Rapid glucocorticoid signaling	21	422	20	-0.01	0.048	1000	-1000	-0.01	-1000
Signaling mediated by p38-alpha and p38-beta	20	901	44	-0.021	0.056	1000	-1000	-0.009	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	20	1414	68	-0.075	0.094	1000	-1000	-0.03	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	20	1598	78	-0.018	0.066	1000	-1000	-0.016	-1000
Effects of Botulinum toxin	19	495	26	-0.01	0.071	1000	-1000	-0.01	-1000
Arf6 trafficking events	18	1295	71	-0.046	0.05	1000	-1000	-0.038	-1000
Aurora C signaling	17	123	7	0	0.064	1000	-1000	0	-1000
Glypican 2 network	17	71	4	0.04	0.054	1000	-1000	0.038	-1000
Visual signal transduction: Cones	15	602	38	-0.01	0.087	1000	-1000	-0.01	-1000
Visual signal transduction: Rods	13	721	52	-0.018	0.098	1000	-1000	-0.003	-1000
Total	6455	351936	7203	-7.1	8.4	131000	-131000	-2.6	-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	82	82
regulation of centriole replication	-0.011	0.01	0	262	-9999	0	262

×

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	-1.1	161	161
PLK1	-0.046	0.3	-10000	0	-1.2	33	33
BIRC5	-0.049	0.32	-10000	0	-1.3	33	33
HSPA1B	-0.35	0.6	-10000	0	-1.1	169	169
MAP2K1	0.002	0.07	-10000	0	-10000	0	0
BRCA2	-0.36	0.61	-10000	0	-1.2	163	163
FOXM1	-0.51	0.88	-10000	0	-1.7	168	168
XRCC1	-0.35	0.6	-10000	0	-1.2	162	162
FOXM1B/p19	-0.43	0.66	-10000	0	-1.3	169	169
Cyclin D1/CDK4	-0.36	0.55	-10000	0	-1	172	172
CDC2	-0.41	0.68	-10000	0	-1.3	177	177
TGFA	-0.32	0.52	-10000	0	-0.98	170	170
SKP2	-0.34	0.61	-10000	0	-1.2	157	157
CCNE1	0.02	0.028	-10000	0	-0.008	251	251
CKS1B	-0.35	0.6	-10000	0	-1.2	161	161
RB1	-0.31	0.48	-10000	0	-0.98	163	163
FOXM1C/SP1	-0.43	0.71	-10000	0	-1.4	169	169
AURKB	-0.094	0.39	-10000	0	-1.2	56	56
CENPF	-0.39	0.63	-10000	0	-1.2	179	179
CDK4	0.007	0.044	0.11	2	-10000	0	2
MYC	-0.34	0.48	-10000	0	-0.96	171	171
CHEK2	0.005	0.065	-10000	0	-10000	0	0
ONECUT1	-0.36	0.57	-10000	0	-1.1	169	169
CDKN2A	0.026	0.02	0.094	1	-0.034	8	9
LAMA4	-0.39	0.63	-10000	0	-1.2	180	180
FOXM1B/HNF6	-0.45	0.71	-10000	0	-1.4	169	169
FOS	-0.42	0.65	-10000	0	-1.2	208	208
SP1	0.036	0.023	-10000	0	-0.033	48	48
CDC25B	-0.35	0.6	-10000	0	-1.2	164	164
response to radiation	-0.005	0.036	0.088	8	-10000	0	8
CENPB	-0.34	0.6	-10000	0	-1.2	157	157
CENPA	-0.35	0.6	-10000	0	-1.2	160	160
NEK2	-0.36	0.61	-10000	0	-1.2	163	163
HIST1H2BA	-0.34	0.6	-10000	0	-1.2	159	159
CCNA2	0.023	0.029	-10000	0	-0.011	204	204
EP300	0.036	0.014	-10000	0	0	72	72
CCNB1/CDK1	-0.48	0.78	-10000	0	-1.5	170	170
CCNB2	-0.38	0.62	0.8	1	-1.2	171	172
CCNB1	-0.39	0.66	-10000	0	-1.3	163	163
ETV5	-0.36	0.64	-10000	0	-1.2	185	185
ESR1	-0.39	0.61	-10000	0	-1.2	178	178
CCND1	-0.36	0.55	-10000	0	-1.1	176	176
GSK3A	0.005	0.062	0.15	2	-10000	0	2
Cyclin A-E1/CDK1-2	-0.006	0.11	-10000	0	-0.17	111	111
CDK2	0.028	0.028	-10000	0	-0.019	129	129
G2/M transition of mitotic cell cycle	-0.007	0.043	0.096	9	-10000	0	9
FOXM1B/Cbp/p300	-0.4	0.66	-10000	0	-1.3	168	168
GAS1	-0.36	0.6	-10000	0	-1.1	168	168
MMP2	-0.43	0.65	-10000	0	-1.2	211	211
RB1/FOXM1C	-0.41	0.59	-10000	0	-1.1	176	176
CREBBP	0.038	0.012	-10000	0	0	49	49

×

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	176	-10000	0	176
TP53	-0.051	0.12	0.18	13	-0.24	141	154
Senescence	-0.062	0.12	0.18	13	-0.24	144	157
Apoptosis	-0.062	0.12	0.18	13	-0.24	144	157
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.005	0.038	0.3	8	-10000	0	8
MDM4	0.038	0.012	-10000	0	0	53	53

×

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	0.029	0.33	0.54	46	-0.52	91	137
HDAC7	-0.001	0.004	-10000	0	-0.037	1	1
HIF1A/ARNT/Cbp/p300/Src-1	0.028	0.32	0.59	9	-0.59	53	62
SMAD4	0.039	0.012	-10000	0	0	49	49
ID2	0.03	0.33	0.55	46	-0.52	89	135
AP1	0.005	0.085	-10000	0	-0.14	119	119
ABCG2	0.022	0.33	0.54	44	-0.53	89	133
HIF1A	0.029	0.1	0.2	39	-0.13	81	120
TFF3	0.009	0.32	0.55	35	-0.53	87	122
GATA2	0.04	0.019	-10000	0	-0.058	12	12
AKT1	0.04	0.096	0.22	29	-0.12	62	91
response to hypoxia	0.005	0.068	0.15	39	-0.11	49	88
MCL1	0.033	0.34	0.54	48	-0.53	90	138
NDRG1	-0.019	0.29	0.52	24	-0.55	80	104
SERPINE1	-0.013	0.3	0.54	25	-0.53	86	111
FECH	0.026	0.33	0.54	48	-0.53	87	135
FURIN	0.032	0.33	0.55	47	-0.53	88	135
NCOA2	0.038	0.015	-10000	0	-0.001	70	70
EP300	0.042	0.11	0.29	35	-0.24	19	54
HMOX1	0.015	0.33	0.55	39	-0.54	90	129
BHLHE40	-0.027	0.3	0.48	43	-0.52	90	133
BHLHE41	-0.027	0.3	0.48	43	-0.52	90	133
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.093	0.16	0.36	16	-0.19	43	59
ENG	0.018	0.11	0.28	10	-0.2	26	36
JUN	0.035	0.019	-10000	0	-0.005	90	90
RORA	0.03	0.33	0.55	45	-0.53	89	134
ABCB1	0.018	0.098	-10000	0	-0.55	4	4
TFRC	-0.009	0.31	0.54	31	-0.54	86	117
CXCR4	0.005	0.33	0.54	40	-0.54	94	134
TF	0.024	0.32	0.54	46	-0.52	87	133
CITED2	0.027	0.33	0.54	44	-0.52	89	133
HIF1A/ARNT	0.015	0.38	-10000	0	-0.66	61	61
LDHA	-0.048	0.3	-10000	0	-0.91	53	53
ETS1	0.006	0.32	0.53	34	-0.54	91	125
PGK1	0.029	0.34	0.54	48	-0.54	91	139
NOS2	-0.027	0.3	0.48	43	-0.52	90	133
ITGB2	0.008	0.33	0.55	39	-0.54	94	133
ALDOA	0.036	0.34	0.54	49	-0.53	87	136
Cbp/p300/CITED2	0.009	0.33	0.57	22	-0.6	72	94
FOS	0.026	0.022	-10000	0	-0.001	210	210
HK2	0.03	0.34	0.55	43	-0.53	89	132
SP1	0.048	0.008	-10000	0	-10000	0	0
GCK	0.064	0.15	0.56	3	-10000	0	3
HK1	0.031	0.34	0.54	49	-0.52	91	140
NPM1	0.035	0.34	0.55	48	-0.53	91	139
EGLN1	0.034	0.33	0.55	48	-0.52	86	134
CREB1	0.035	0.042	-10000	0	-0.11	41	41
PGM1	0.023	0.34	0.54	44	-0.54	90	134
SMAD3	0.04	0.009	-10000	0	0	25	25
EDN1	0.034	0.21	0.46	4	-1	13	17
IGFBP1	0.036	0.34	0.54	48	-0.53	88	136
VEGFA	-0.01	0.26	0.47	31	-0.51	62	93
HIF1A/JAB1	0.033	0.098	0.2	9	-0.15	69	78
CP	-0.016	0.31	0.52	33	-0.55	88	121
CXCL12	-0.023	0.31	0.53	25	-0.53	96	121
COPS5	0.036	0.016	-10000	0	-0.001	85	85
SMAD3/SMAD4	0.052	0.033	-10000	0	-0.14	11	11
BNIP3	0.012	0.33	0.55	38	-0.54	89	127
EGLN3	-0.021	0.32	0.54	28	-0.56	94	122
CA9	-0.019	0.3	0.54	25	-0.53	88	113
TERT	0.018	0.32	0.54	40	-0.53	85	125
ENO1	0.031	0.34	0.55	46	-0.53	90	136
PFKL	0.033	0.34	0.55	45	-0.53	89	134
NCOA1	0.04	0.01	-10000	0	-0.001	29	29
ADM	-0.003	0.32	0.54	25	-0.54	90	115
ARNT	0.03	0.098	0.2	38	-0.12	93	131
HNF4A	0.042	0.011	-10000	0	-10000	0	0
ADFP	-0.004	0.32	0.53	36	-0.53	95	131
SLC2A1	0.002	0.28	0.49	20	-0.54	65	85
LEP	0.035	0.33	0.54	49	-0.53	85	134
HIF1A/ARNT/Cbp/p300	0.01	0.32	0.59	5	-0.61	54	59
EPO	0.03	0.28	0.51	22	-0.54	50	72
CREBBP	0.048	0.11	0.28	45	-0.21	15	60
HIF1A/ARNT/Cbp/p300/HDAC7	0.003	0.31	0.56	1	-0.6	56	57
PFKFB3	0.025	0.33	0.53	50	-0.54	87	137
NT5E	-0.041	0.3	0.52	18	-0.55	98	116

×

Wnt 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	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	173	173
WNT6	0.041	0.006	-9999	0	12	12
WNT4	0.04	0.008	-9999	0	19	19
FZD3	0.029	0.019	-9999	0	166	166
WNT5A	0.035	0.015	-9999	0	90	90
WNT11	0.033	0.017	-9999	0	122	122

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.031	0.018	-10000	0	0	141	141
EPHB2	0.042	0.013	0.067	3	0	38	41
EFNB1	-0.001	0.024	0.029	203	-10000	0	203
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.077	0.066	0.23	1	-0.2	2	3
Ephrin B2/EPHB1-2	0.041	0.069	-10000	0	-0.1	77	77
neuron projection morphogenesis	0.052	0.051	-10000	0	-0.12	13	13
Ephrin B1/EPHB1-2/Tiam1	0.071	0.061	0.23	1	-0.12	22	23
DNM1	0.041	0.011	-10000	0	0	36	36
cell-cell signaling	0.003	0.006	0.025	1	-10000	0	1
MAP2K4	-0.14	0.21	0.26	1	-0.46	162	163
YES1	-0.2	0.33	-10000	0	-0.69	167	167
Ephrin B1/EPHB1-2/NCK2	0.079	0.053	0.22	2	-0.12	12	14
PI3K	-0.11	0.23	-10000	0	-0.44	164	164
mol:GDP	0.068	0.059	0.22	1	-0.12	22	23
ITGA2B	0.04	0.009	-10000	0	0	29	29
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	-0.14	0.23	0.22	4	-0.49	159	163
FGR	-0.19	0.32	-10000	0	-0.68	170	170
TIAM1	0.037	0.014	-10000	0	0	70	70
PIK3R1	0.034	0.016	-10000	0	0	106	106
RGS3	0.04	0.008	-10000	0	0	21	21
cell adhesion	-0.11	0.21	-10000	0	-0.42	163	163
LYN	-0.19	0.33	-10000	0	-0.7	161	161
Ephrin B1/EPHB1-2/Src Family Kinases	-0.18	0.3	-10000	0	-0.62	169	169
Ephrin B1/EPHB1-2	-0.14	0.24	-10000	0	-0.53	151	151
SRC	-0.19	0.32	-10000	0	-0.68	166	166
ITGB3	0.033	0.017	-10000	0	0	120	120
EPHB1	0.04	0.014	-10000	0	0	57	57
EPHB4	0.04	0.009	-10000	0	0	27	27
RAC1	0.039	0.01	-10000	0	0	35	35
Ephrin B2/EPHB4	0.025	0.061	-10000	0	-0.11	83	83
alphaIIb/beta3 Integrin	0.039	0.05	-10000	0	-0.14	34	34
BLK	-0.2	0.32	-10000	0	-0.69	163	163
HCK	-0.19	0.32	-10000	0	-0.68	164	164
regulation of stress fiber formation	-0.077	0.051	0.12	12	-0.22	2	14
MAPK8	-0.14	0.21	0.24	1	-0.44	164	165
Ephrin B1/EPHB1-2/RGS3	0.08	0.052	0.22	2	-0.12	13	15
endothelial cell migration	-0.11	0.18	0.19	4	-0.4	144	148
NCK2	0.041	0.006	-10000	0	0	10	10
PTPN13	0.021	0.022	-10000	0	0	276	276
regulation of focal adhesion formation	-0.077	0.051	0.12	12	-0.22	2	14
chemotaxis	-0.077	0.051	0.12	13	-0.22	2	15
PIK3CA	0.03	0.019	-10000	0	0	150	150
Rac1/GTP	0.065	0.059	0.2	1	-0.13	8	9
angiogenesis	-0.14	0.24	-10000	0	-0.52	156	156
LCK	-0.19	0.32	-10000	0	-0.68	168	168

×

Endothelins

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
AKT1	-0.004	0.14	0.23	33	-0.24	113	146
PTK2B	0.033	0.017	-10000	0	0	116	116
mol:Ca2+	-0.034	0.2	0.4	1	-0.48	56	57
EDN1	-0.005	0.1	0.22	7	-0.18	120	127
EDN3	0.036	0.015	-10000	0	0	79	79
EDN2	0.037	0.014	-10000	0	0	67	67
HRAS/GDP	-0.053	0.19	0.26	4	-0.35	116	120
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.032	0.14	0.19	5	-0.27	105	110
ADCY4	0.009	0.13	0.21	65	-0.23	67	132
ADCY5	0.008	0.13	0.21	61	-0.23	68	129
ADCY6	0.008	0.14	0.21	69	-0.23	72	141
ADCY7	0.005	0.13	0.21	60	-0.24	70	130
ADCY1	0.008	0.14	0.2	67	-0.24	70	137
ADCY2	0.01	0.13	0.21	60	-0.23	58	118
ADCY3	0.007	0.14	0.2	69	-0.24	70	139
ADCY8	-0.003	0.1	0.22	29	-0.23	48	77
ADCY9	0.008	0.14	0.21	67	-0.23	73	140
arachidonic acid secretion	-0.1	0.26	0.29	3	-0.48	144	147
ETB receptor/Endothelin-1/Gq/GTP	-0.003	0.11	0.16	1	-0.22	72	73
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.039	0.009	-10000	0	0	29	29
ETA receptor/Endothelin-1/G12/GTP	-0.007	0.13	0.35	6	-0.22	118	124
ETA receptor/Endothelin-1/Gs/GTP	-0.005	0.12	0.32	7	-0.2	116	123
mol:GTP	0	0.006	-10000	0	-0.024	4	4
COL3A1	-0.057	0.16	0.25	10	-0.35	113	123
EDNRB	0.021	0.054	0.091	4	-0.089	93	97
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.003	0.14	0.25	13	-0.26	95	108
CYSLTR1	-0.015	0.15	0.27	8	-0.29	80	88
SLC9A1	-0.016	0.084	0.2	7	-0.17	87	94
mol:GDP	-0.067	0.19	0.24	6	-0.36	120	126
SLC9A3	-0.024	0.19	-10000	0	-0.48	47	47
RAF1	-0.079	0.22	0.25	5	-0.41	139	144
JUN	-0.075	0.3	-10000	0	-0.74	70	70
JAK2	-0.008	0.14	0.22	28	-0.24	109	137
mol:IP3	-0.026	0.15	0.2	5	-0.3	85	90
ETA receptor/Endothelin-1	-0.027	0.15	0.39	6	-0.27	125	131
PLCB1	0.034	0.016	-10000	0	0	104	104
PLCB2	0.037	0.015	-10000	0	-0.005	55	55
ETA receptor/Endothelin-3	0.014	0.084	0.19	7	-0.13	96	103
FOS	-0.14	0.36	-10000	0	-0.82	112	112
Gai/GDP	-0.029	0.23	-10000	0	-0.68	56	56
CRK	0.039	0.011	-10000	0	0	45	45
mol:Ca ++	-0.033	0.19	0.24	36	-0.34	114	150
BCAR1	0.036	0.014	-10000	0	0	74	74
PRKCB1	-0.029	0.14	0.22	10	-0.29	88	98
GNAQ	0.035	0.022	-10000	0	-0.039	30	30
GNAZ	0.039	0.011	-10000	0	0	38	38
GNAL	0.04	0.009	-10000	0	0	27	27
Gs family/GDP	-0.053	0.18	0.24	4	-0.33	116	120
ETA receptor/Endothelin-1/Gq/GTP	-0.019	0.14	0.21	6	-0.26	93	99
MAPK14	-0.021	0.11	0.22	3	-0.24	75	78
TRPC6	-0.037	0.21	0.4	1	-0.51	52	53
GNAI2	0.041	0.006	-10000	0	0	13	13
GNAI3	0.038	0.012	-10000	0	0	46	46
GNAI1	0.035	0.016	-10000	0	0	94	94
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.015	0.11	-10000	0	-0.24	76	76
ETB receptor/Endothelin-2	0.03	0.054	-10000	0	-0.071	89	89
ETB receptor/Endothelin-3	0.032	0.051	-10000	0	-0.067	78	78
ETB receptor/Endothelin-1	0.006	0.1	0.2	5	-0.19	97	102
MAPK3	-0.13	0.34	0.32	1	-0.76	115	116
MAPK1	-0.14	0.35	0.32	1	-0.75	120	121
Rac1/GDP	-0.054	0.19	0.26	3	-0.35	114	117
cAMP biosynthetic process	0.044	0.13	0.23	74	-0.22	34	108
MAPK8	-0.054	0.24	-10000	0	-0.52	84	84
SRC	0.04	0.01	-10000	0	0	31	31
ETB receptor/Endothelin-1/Gi/GTP	-0.01	0.11	-10000	0	-0.26	61	61
p130Cas/CRK/Src/PYK2	-0.063	0.2	0.3	5	-0.39	102	107
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.055	0.19	0.26	3	-0.35	116	119
COL1A2	-0.073	0.21	0.27	5	-0.48	102	107
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.011	0.088	0.19	8	-0.14	113	121
mol:DAG	-0.027	0.15	0.2	5	-0.3	86	91
MAP2K2	-0.1	0.27	0.29	2	-0.55	126	128
MAP2K1	-0.11	0.27	0.29	2	-0.55	129	131
EDNRA	-0.003	0.1	0.22	8	-0.17	131	139
positive regulation of muscle contraction	-0.013	0.12	0.2	31	-0.22	90	121
Gq family/GDP	-0.015	0.19	0.28	1	-0.32	114	115
HRAS/GTP	-0.056	0.18	0.24	3	-0.34	122	125
PRKCH	-0.034	0.15	0.26	2	-0.29	96	98
RAC1	0.039	0.01	-10000	0	0	35	35
PRKCA	-0.033	0.15	0.23	5	-0.3	91	96
PRKCB	-0.031	0.15	0.19	5	-0.29	99	104
PRKCE	-0.031	0.14	0.27	5	-0.29	88	93
PRKCD	-0.034	0.15	0.22	3	-0.3	88	91
PRKCG	-0.037	0.15	0.2	1	-0.3	97	98
regulation of vascular smooth muscle contraction	-0.18	0.44	-10000	0	-1	110	110
PRKCQ	-0.033	0.15	0.28	11	-0.3	94	105
PLA2G4A	-0.12	0.28	0.29	3	-0.52	144	147
GNA14	0.036	0.021	-10000	0	-0.039	31	31
GNA15	0.034	0.022	-10000	0	-0.036	28	28
GNA12	0.039	0.01	-10000	0	0	36	36
GNA11	0.034	0.022	-10000	0	-0.036	29	29
Rac1/GTP	-0.006	0.13	0.35	6	-0.22	115	121
MMP1	0.022	0.13	0.32	24	-0.58	10	34

×

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	0.02	0.081	-10000	0	-0.13	113	113
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.11	0.21	3	-0.24	60	63
AP1	-0.027	0.068	-10000	0	-0.12	171	171
mol:PIP3	-0.037	0.057	-10000	0	-0.13	127	127
AKT1	-0.006	0.095	0.24	16	-0.23	21	37
PTK2B	-0.047	0.11	0.12	3	-0.19	180	183
RHOA	0.001	0.06	0.17	1	-0.32	8	9
PIK3CB	0.034	0.016	-10000	0	0	99	99
mol:Ca2+	-0.01	0.048	0.19	8	-0.14	21	29
MAGI3	0.039	0.01	-10000	0	0	33	33
RELA	0.041	0.006	-10000	0	0	10	10
apoptosis	0.001	0.069	0.072	118	-0.14	95	213
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.047	0.1	0.19	18	-0.21	107	125
NF kappa B1 p50/RelA	-0.03	0.076	0.11	2	-0.16	113	115
endothelial cell migration	-0.042	0.12	-10000	0	-0.3	101	101
ADCY4	-0.02	0.095	0.18	3	-0.2	99	102
ADCY5	-0.02	0.094	0.16	4	-0.19	104	108
ADCY6	-0.02	0.095	0.17	3	-0.2	104	107
ADCY7	-0.019	0.093	0.15	5	-0.19	100	105
ADCY1	-0.018	0.092	0.18	3	-0.19	99	102
ADCY2	-0.014	0.09	0.17	1	-0.19	89	90
ADCY3	-0.021	0.095	0.19	2	-0.2	106	108
ADCY8	-0.003	0.087	0.19	2	-0.19	76	78
ADCY9	-0.023	0.099	0.18	3	-0.2	108	111
GSK3B	-0.046	0.11	0.2	17	-0.2	128	145
arachidonic acid secretion	-0.031	0.097	0.14	2	-0.19	125	127
GNG2	0.039	0.01	-10000	0	0	34	34
TRIP6	0.012	0.051	-10000	0	-0.24	18	18
GNAO1	0.004	0.072	0.089	111	-0.14	96	207
HRAS	0.04	0.009	-10000	0	0	29	29
NFKBIA	-0.031	0.092	0.17	9	-0.26	47	56
GAB1	0.038	0.012	-10000	0	0	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.013	0.26	-10000	0	-0.88	47	47
JUN	0.036	0.015	-10000	0	0	80	80
LPA/LPA2/NHERF2	0.015	0.037	-10000	0	-0.062	96	96
TIAM1	-0.039	0.3	-10000	0	-1	47	47
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	-0.005	0.044	0.19	8	-0.14	14	22
PLCB3	0.015	0.044	0.17	11	-0.062	93	104
FOS	0.026	0.02	-10000	0	0	205	205
positive regulation of mitosis	-0.031	0.097	0.14	2	-0.19	125	127
LPA/LPA1-2-3	-0.018	0.05	-10000	0	-0.12	102	102
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	74	74
stress fiber formation	-0.012	0.1	-10000	0	-0.25	47	47
GNAZ	0.007	0.074	0.09	119	-0.15	90	209
EGFR/PI3K-beta/Gab1	-0.026	0.066	-10000	0	-0.13	129	129
positive regulation of dendritic cell cytokine production	-0.018	0.05	-10000	0	-0.12	102	102
LPA/LPA2/MAGI-3	0.015	0.037	-10000	0	-0.061	98	98
ARHGEF1	0.005	0.076	0.2	11	-0.14	90	101
GNAI2	0.005	0.077	0.09	122	-0.14	100	222
GNAI3	0.003	0.079	0.09	118	-0.15	99	217
GNAI1	0.002	0.079	0.09	116	-0.16	95	211
LPA/LPA3	-0.011	0.026	-10000	0	-0.065	102	102
LPA/LPA2	-0.011	0.026	-10000	0	-0.064	102	102
LPA/LPA1	-0.025	0.068	-10000	0	-0.17	102	102
HB-EGF/EGFR	0.023	0.052	-10000	0	-0.13	49	49
HBEGF	-0.014	0.01	-10000	0	-10000	0	0
mol:DAG	-0.005	0.044	0.19	8	-0.14	14	22
cAMP biosynthetic process	-0.023	0.097	0.2	5	-0.2	98	103
NFKB1	0.035	0.015	-10000	0	0	85	85
SRC	0.039	0.01	-10000	0	0	31	31
GNB1	0.041	0.005	-10000	0	0	7	7
LYN	-0.025	0.094	0.17	14	-0.23	58	72
GNAQ	0.008	0.032	0.043	118	-0.053	103	221
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.017	0.041	-10000	0	-0.1	102	102
IL8	-0.026	0.18	0.25	7	-0.37	92	99
PTK2	0.005	0.061	0.093	78	-0.12	76	154
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
CASP3	0.001	0.069	0.072	118	-0.14	95	213
EGFR	0.036	0.014	-10000	0	0	73	73
PLCG1	0.005	0.037	-10000	0	-0.086	38	38
PLD2	0.015	0.067	0.093	121	-0.12	94	215
G12/G13	0.021	0.079	-10000	0	-0.14	102	102
PI3K-beta	-0.028	0.076	-10000	0	-0.21	47	47
cell migration	-0.01	0.086	-10000	0	-0.25	46	46
SLC9A3R2	0.038	0.012	-10000	0	0	51	51
PXN	-0.013	0.1	-10000	0	-0.25	47	47
HRAS/GTP	-0.03	0.098	0.14	2	-0.19	122	124
RAC1	0.039	0.01	-10000	0	0	35	35
MMP9	0.029	0.019	-10000	0	0	170	170
PRKCE	0.039	0.011	-10000	0	0	38	38
PRKCD	-0.016	0.055	0.18	12	-0.16	20	32
Gi(beta/gamma)	-0.021	0.1	0.15	1	-0.19	120	121
mol:LPA	-0.017	0.041	-10000	0	-0.1	102	102
TRIP6/p130 Cas/FAK1/Paxillin	-0.007	0.1	0.19	1	-0.23	53	54
MAPKKK cascade	-0.031	0.097	0.14	2	-0.19	125	127
contractile ring contraction involved in cytokinesis	0.001	0.062	0.16	2	-0.3	10	12
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.033	0.043	118	-0.052	110	228
GNA15	0.008	0.031	0.043	112	-0.054	96	208
GNA12	0.039	0.01	-10000	0	0	36	36
GNA13	0.04	0.009	-10000	0	0	28	28
MAPT	-0.047	0.11	0.19	18	-0.21	108	126
GNA11	0.008	0.032	0.043	112	-0.054	99	211
Rac1/GTP	-0.016	0.28	-10000	0	-0.93	47	47
MMP2	-0.042	0.12	-10000	0	-0.3	101	101

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.012	0.13	0.21	9	-0.22	110	119
NF kappa B1 p50/RelA/I kappa B alpha	-0.048	0.19	0.28	1	-0.36	117	118
alphaV/beta3 Integrin/Osteopontin/Src	-0.008	0.11	-10000	0	-0.17	150	150
AP1	-0.046	0.18	0.27	2	-0.28	151	153
ILK	-0.028	0.11	0.2	10	-0.24	71	81
bone resorption	-0.04	0.1	0.19	2	-0.25	57	59
PTK2B	0.033	0.017	-10000	0	0	116	116
PYK2/p130Cas	0.004	0.12	-10000	0	-0.2	78	78
ITGAV	0.026	0.032	-10000	0	-0.048	63	63
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.029	0.067	-10000	0	-0.14	66	66
alphaV/beta3 Integrin/Osteopontin	0.004	0.13	-10000	0	-0.17	158	158
MAP3K1	-0.027	0.11	0.18	11	-0.24	69	80
JUN	0.036	0.015	-10000	0	0	80	80
MAPK3	-0.047	0.14	0.19	14	-0.28	111	125
MAPK1	-0.046	0.14	0.19	15	-0.28	110	125
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
NFKB1	0.035	0.015	-10000	0	0	85	85
MAPK8	-0.032	0.1	0.18	11	-0.24	71	82
ITGB3	0.023	0.034	-10000	0	-0.048	75	75
NFKBIA	-0.064	0.17	0.19	7	-0.36	108	115
FOS	0.026	0.02	-10000	0	0	205	205
CD44	0.035	0.016	-10000	0	0	94	94
CHUK	0.038	0.012	-10000	0	0	52	52
PLAU	-0.18	0.42	-10000	0	-1	109	109
NF kappa B1 p50/RelA	-0.033	0.2	-10000	0	-0.37	120	120
BCAR1	0.036	0.014	-10000	0	0	74	74
RELA	0.041	0.006	-10000	0	0	10	10
alphaV beta3 Integrin	0.004	0.091	-10000	0	-0.16	108	108
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.03	0.1	0.19	11	-0.23	73	84
VAV3	-0.039	0.1	0.18	10	-0.23	88	98
MAP3K14	-0.026	0.12	0.19	12	-0.23	107	119
ROCK2	0.037	0.013	-10000	0	0	62	62
SPP1	0.024	0.031	-10000	0	-0.05	51	51
RAC1	0.039	0.01	-10000	0	0	35	35
Rac1/GTP	-0.035	0.11	0.18	11	-0.22	86	97
MMP2	-0.088	0.14	0.25	2	-0.31	133	135

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.037	0.013	-10000	0	0	61	61
CCL5	0.03	0.019	-10000	0	0	162	162
SDCBP	0.036	0.014	-10000	0	0	77	77
FGFR/FGF2/Syndecan-1	-0.014	0.12	0.2	21	-0.33	39	60
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	-0.014	0.13	0.21	16	-0.3	55	71
Syndecan-1/Syntenin	-0.016	0.14	0.22	20	-0.29	65	85
MAPK3	-0.024	0.13	0.2	19	-0.28	61	80
HGF/MET	0.013	0.075	-10000	0	-0.14	104	104
TGFB1/TGF beta receptor Type II	0.037	0.013	-10000	0	0	61	61
BSG	0.036	0.014	-10000	0	0	75	75
keratinocyte migration	-0.014	0.13	0.21	16	-0.3	55	71
Syndecan-1/RANTES	-0.019	0.14	0.23	20	-0.29	75	95
Syndecan-1/CD147	-0.004	0.15	0.25	13	-0.3	58	71
Syndecan-1/Syntenin/PIP2	-0.018	0.14	0.21	20	-0.28	65	85
LAMA5	0.035	0.015	-10000	0	0	90	90
positive regulation of cell-cell adhesion	-0.018	0.13	0.21	20	-0.28	65	85
MMP7	0.016	0.02	-10000	0	0	336	336
HGF	0.04	0.009	-10000	0	0	29	29
Syndecan-1/CASK	-0.038	0.12	-10000	0	-0.29	60	60
Syndecan-1/HGF/MET	-0.02	0.14	0.25	14	-0.29	71	85
regulation of cell adhesion	-0.032	0.12	0.19	15	-0.28	56	71
HPSE	0.035	0.015	-10000	0	0	89	89
positive regulation of cell migration	-0.014	0.12	0.2	21	-0.33	39	60
SDC1	-0.019	0.12	0.17	6	-0.34	36	42
Syndecan-1/Collagen	-0.014	0.12	0.2	21	-0.33	39	60
PPIB	0.04	0.009	-10000	0	0	24	24
MET	0.027	0.02	-10000	0	0	195	195
PRKACA	0.035	0.015	-10000	0	0	87	87
MMP9	0.029	0.019	-10000	0	0	170	170
MAPK1	-0.023	0.13	0.2	18	-0.28	62	80
homophilic cell adhesion	-0.013	0.13	0.2	29	-0.32	43	72
MMP1	0.03	0.019	-10000	0	0	155	155

×

LPA4-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
ADCY4	-0.014	0.006	0	75	-10000	0	75
ADCY5	-0.014	0.006	0	88	-10000	0	88
ADCY6	-0.015	0.005	0	58	-10000	0	58
ADCY7	-0.014	0.006	0	81	-10000	0	81
ADCY1	-0.015	0.005	0	54	-10000	0	54
ADCY2	-0.014	0.006	0	102	-10000	0	102
ADCY3	-0.015	0.005	0	55	-10000	0	55
ADCY8	-0.008	0.008	0	284	-10000	0	284
PRKCE	-0.01	0.003	0	38	-10000	0	38
ADCY9	-0.014	0.006	0	77	-10000	0	77
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.058	0.086	0.2	87	-0.19	4	91

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.005	0.086	-10000	0	-0.13	129	129
alphaM/beta2 Integrin/GPIbA	0.053	0.069	-10000	0	-0.11	65	65
alphaM/beta2 Integrin/proMMP-9	0.03	0.082	-10000	0	-0.13	84	84
PLAUR	0.036	0.014	-10000	0	0	74	74
HMGB1	0.041	0.016	-10000	0	-0.054	10	10
alphaM/beta2 Integrin/Talin	0.047	0.076	-10000	0	-0.12	81	81
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	0.081	0.083	-10000	0	-0.12	55	55
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.029	0.019	-10000	0	0	170	170
CYR61	0.03	0.019	-10000	0	0	156	156
TLN1	0.038	0.012	-10000	0	0	47	47
Rap1/GTP	-0.061	0.17	-10000	0	-0.31	140	140
RHOA	0.041	0.007	-10000	0	0	14	14
P-selectin oligomer	0.039	0.011	-10000	0	0	39	39
MYH2	-0.081	0.17	0.21	1	-0.34	133	134
MST1R	0.039	0.011	-10000	0	0	41	41
leukocyte activation during inflammatory response	0.058	0.065	-10000	0	-0.1	51	51
APOB	0.041	0.007	-10000	0	0	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.021	0.021	-10000	0	0	269	269
JAM3	0.038	0.013	-10000	0	0	56	56
GP1BA	0.039	0.01	-10000	0	0	31	31
alphaM/beta2 Integrin/CTGF	0.034	0.081	-10000	0	-0.12	96	96
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	40	40
ICAM1	0.026	0.02	-10000	0	0	206	206
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.063	0.17	-10000	0	-0.34	122	122
cell adhesion	0.052	0.068	-10000	0	-0.11	65	65
NFKB1	0.021	0.075	0.25	5	-0.22	24	29
THY1	0.025	0.02	-10000	0	0	217	217
RhoA/GDP	0.029	0.014	-10000	0	-0.13	4	4
Lipoprotein(a)	0.049	0.019	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.024	0.1	-10000	0	-0.13	136	136
IL6	-0.019	0.076	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	0.066	0.074	-10000	0	-0.11	56	56
JAM2	0.037	0.013	-10000	0	0	59	59
alphaM/beta2 Integrin/ICAM1	0.052	0.1	-10000	0	-0.14	95	95
alphaM/beta2 Integrin/uPA/Plg	0.041	0.098	-10000	0	-0.14	100	100
RhoA/GTP	-0.082	0.18	0.2	1	-0.35	138	139
positive regulation of phagocytosis	-0.043	0.15	0.21	4	-0.28	116	120
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	0.081	-10000	0	-0.14	73	73
PLAU	0.026	0.02	-10000	0	0	212	212
PLAT	0.026	0.02	-10000	0	0	213	213
actin filament polymerization	-0.077	0.16	0.2	1	-0.33	132	133
MST1	0.041	0.007	-10000	0	0	15	15
alphaM/beta2 Integrin/lipoprotein(a)	0.064	0.068	-10000	0	-0.1	51	51
TNF	-0.011	0.072	0.26	4	-0.32	9	13
RAP1B	0.038	0.013	-10000	0	0	57	57
alphaM/beta2 Integrin/uPA	0.017	0.094	-10000	0	-0.15	109	109
fibrinolysis	0.038	0.097	-10000	0	-0.14	100	100
HCK	0.036	0.015	-10000	0	0	79	79
dendritic cell antigen processing and presentation	-0.063	0.17	-10000	0	-0.34	122	122
VTN	0.04	0.008	-10000	0	0	21	21
alphaM/beta2 Integrin/CYR61	0.024	0.084	-10000	0	-0.12	115	115
LPA	0.037	0.013	-10000	0	0	58	58
LRP1	0.036	0.014	-10000	0	0	73	73
cell migration	0.017	0.095	0.19	12	-0.13	131	143
FN1	0.021	0.021	-10000	0	0	273	273
alphaM/beta2 Integrin/Thy1	0.008	0.092	-10000	0	-0.12	152	152
MPO	0.04	0.008	-10000	0	0	19	19
KNG1	0.034	0.017	-10000	0	0	108	108
RAP1/GDP	0.039	0.049	-10000	0	-0.12	41	41
ROCK1	-0.082	0.17	0.24	3	-0.34	138	141
ELA2	0.037	0.014	-10000	0	0	70	70
PLG	0.038	0.012	-10000	0	0	50	50
CTGF	0.033	0.017	-10000	0	0	113	113
alphaM/beta2 Integrin/Hck	0.049	0.073	-10000	0	-0.13	60	60
ITGAM	0.041	0.016	-10000	0	-0.054	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.072	0.076	-10000	0	-0.12	55	55
HP	0.01	0.018	-10000	0	0	419	419
leukocyte adhesion	0.019	0.11	-10000	0	-0.17	58	58
SELP	0.039	0.011	-10000	0	0	39	39

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	92	92
PTK2	-0.045	0.13	-10000	0	-0.31	95	95
positive regulation of JNK cascade	-0.032	0.14	-10000	0	-0.28	106	106
CDC42/GDP	-0.038	0.2	-10000	0	-0.36	124	124
Rac1/GDP	-0.04	0.19	-10000	0	-0.36	118	118
RAP1B	0.038	0.013	-10000	0	0	57	57
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.039	0.01	-10000	0	0	32	32
CDC42/GTP	-0.037	0.18	-10000	0	-0.34	104	104
nectin-3/I-afadin	0.01	0.074	-10000	0	-0.14	96	96
RAPGEF1	-0.058	0.18	-10000	0	-0.37	124	124
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.064	0.2	-10000	0	-0.4	126	126
PDGFB-D/PDGFRB	0.037	0.013	-10000	0	0	64	64
TLN1	-0.04	0.084	0.19	1	-0.25	60	61
Rap1/GTP	-0.046	0.14	-10000	0	-0.28	126	126
IQGAP1	0.037	0.014	-10000	0	0	67	67
Rap1/GTP/I-afadin	0.042	0.065	-10000	0	-0.11	64	64
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.01	0.074	-10000	0	-0.14	96	96
PVR	0.04	0.009	-10000	0	0	24	24
Necl-5(dimer)	0.04	0.009	-10000	0	0	24	24
mol:GDP	-0.066	0.22	-10000	0	-0.42	124	124
MLLT4	0.033	0.017	-10000	0	0	110	110
PIK3CA	0.03	0.019	-10000	0	0	150	150
PI3K	0.024	0.091	-10000	0	-0.13	97	97
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.041	0.046	-10000	0	-0.14	26	26
positive regulation of lamellipodium assembly	-0.04	0.15	-10000	0	-0.29	121	121
PVRL1	0.04	0.008	-10000	0	0	23	23
PVRL3	0.029	0.019	-10000	0	0	169	169
PVRL2	0.039	0.011	-10000	0	0	43	43
PIK3R1	0.034	0.016	-10000	0	0	106	106
CDH1	0.035	0.016	-10000	0	0	96	96
CLDN1	0.023	0.021	-10000	0	0	253	253
JAM-A/CLDN1	0.013	0.089	-10000	0	-0.12	124	124
SRC	-0.083	0.21	-10000	0	-0.44	130	130
ITGB3	0.033	0.017	-10000	0	0	120	120
nectin-1(dimer)/I-afadin/I-afadin	0.041	0.046	-10000	0	-0.14	26	26
FARP2	-0.059	0.22	-10000	0	-0.44	95	95
RAC1	0.039	0.01	-10000	0	0	35	35
CTNNA1	0.039	0.01	-10000	0	0	36	36
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.024	0.077	-10000	0	-0.12	96	96
nectin-1/I-afadin	0.041	0.046	-10000	0	-0.14	26	26
nectin-2/I-afadin	0.038	0.05	-10000	0	-0.14	31	31
RAC1/GTP/IQGAP1/filamentous actin	0.038	0.046	-10000	0	-0.11	40	40
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.024	0.076	-10000	0	-0.12	92	92
CDC42/GTP/IQGAP1/filamentous actin	0.04	0.046	-10000	0	-0.11	40	40
F11R	0.04	0.009	-10000	0	0	29	29
positive regulation of filopodium formation	-0.032	0.14	-10000	0	-0.28	106	106
alphaV/beta3 Integrin/Talin	-0.031	0.11	0.26	2	-0.23	94	96
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.05	-10000	0	-0.14	31	31
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.05	-10000	0	-0.14	31	31
PIP5K1C	-0.031	0.086	-10000	0	-0.18	113	113
VAV2	-0.073	0.23	-10000	0	-0.46	107	107
RAP1/GDP	-0.039	0.18	-10000	0	-0.34	122	122
ITGAV	0.033	0.017	-10000	0	0	115	115
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.021	0.077	-10000	0	-0.12	98	98
nectin-3(dimer)/I-afadin/I-afadin	0.01	0.074	-10000	0	-0.14	96	96
Rac1/GTP	-0.047	0.19	-10000	0	-0.35	121	121
PTPRM	-0.027	0.096	-10000	0	-0.18	116	116
E-cadherin/beta catenin/alpha catenin	0.062	0.09	-10000	0	-0.13	54	54
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.04	0.008	-10000	0	0	22	22

×

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	0.026	-10000	0	-0.047	40	40
CDKN2C	0.029	0.029	-10000	0	-0.046	48	48
CDKN2A	0.021	0.029	-10000	0	-0.039	59	59
CCND2	0.009	0.046	0.11	78	-0.12	2	80
RB1	-0.012	0.066	0.24	6	-0.14	84	90
CDK4	0.01	0.056	0.13	79	-0.12	20	99
CDK6	0.006	0.063	0.13	79	-0.12	44	123
G1/S progression	0.019	0.074	0.14	106	-0.23	8	114

×

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	271	271
positive regulation of NF-kappaB transcription factor activity	0.003	0.066	-10000	0	-0.13	92	92
MAP2K4	-0.014	0.095	0.18	1	-0.27	38	39
IKBKB	0.038	0.011	-10000	0	0	44	44
TNFRSF10B	0.033	0.017	-10000	0	0	123	123
TNFRSF10A	0.031	0.018	-10000	0	0	138	138
SMPD1	-0.007	0.044	-10000	0	-0.1	90	90
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	134	134
TRAIL/TRAILR2	0.003	0.067	-10000	0	-0.13	93	93
TRAIL/TRAILR3	0.002	0.067	-10000	0	-0.13	97	97
TRAIL/TRAILR1	0	0.068	-10000	0	-0.13	98	98
TRAIL/TRAILR4	0.003	0.067	-10000	0	-0.13	92	92
TRAIL/TRAILR1/DAP3/GTP	0.011	0.066	-10000	0	-0.1	97	97
IKK complex	0.021	0.089	-10000	0	-0.32	20	20
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	-0.007	0.098	-10000	0	-0.28	36	36
TRAILR4 (trimer)	0.032	0.018	-10000	0	0	134	134
TRADD	0.036	0.014	-10000	0	0	76	76
TRAILR1 (trimer)	0.031	0.018	-10000	0	0	138	138
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.022	0.082	-10000	0	-0.18	93	93
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	0.027	0.082	-10000	0	-0.11	84	84
mol:ceramide	-0.007	0.044	-10000	0	-0.1	90	90
FADD	0.04	0.008	-10000	0	0	21	21
MAPK8	-0.021	0.099	0.2	5	-0.27	45	50
TRAF2	0.04	0.009	-10000	0	0	25	25
TRAILR3 (trimer)	0.032	0.018	-10000	0	0	131	131
CHUK	0.038	0.012	-10000	0	0	52	52
TRAIL/TRAILR1/FADD	0.011	0.07	-10000	0	-0.12	95	95
DAP3	0.039	0.011	-10000	0	0	38	38
CASP10	-0.007	0.1	0.16	79	-0.2	77	156
JNK cascade	0.003	0.066	-10000	0	-0.13	92	92
TRAIL (trimer)	0.021	0.021	-10000	0	0	271	271
TNFRSF10C	0.032	0.018	-10000	0	0	131	131
TRAIL/TRAILR1/DAP3/GTP/FADD	0.022	0.073	-10000	0	-0.1	93	93
TRAIL/TRAILR2/FADD	0.014	0.069	-10000	0	-0.11	91	91
cell death	-0.007	0.044	-10000	0	-0.1	90	90
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.021	0.082	-10000	0	-0.18	90	90
TRAILR2 (trimer)	0.032	0.017	-10000	0	0	123	123
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	0.029	0.082	-10000	0	-0.11	60	60

×

PDGFR-alpha signaling pathway

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
PDGFRA	0.018	0.035	-10000	0	-0.055	77	77
PDGF/PDGFRA/CRKL	0.012	0.071	-10000	0	-0.14	81	81
positive regulation of JUN kinase activity	0.048	0.082	-10000	0	-0.12	94	94
CRKL	0.039	0.01	-10000	0	0	35	35
PDGF/PDGFRA/Caveolin-3	0.012	0.073	-10000	0	-0.14	86	86
AP1	-0.12	0.26	-10000	0	-0.66	98	98
mol:IP3	-0.016	0.046	0.074	28	-0.098	81	109
PLCG1	-0.016	0.046	0.074	28	-0.098	81	109
PDGF/PDGFRA/alphaV Integrin	-0.008	0.091	-10000	0	-0.16	127	127
RAPGEF1	0.04	0.008	-10000	0	0	22	22
CRK	0.038	0.011	-10000	0	0	45	45
mol:Ca2+	-0.016	0.046	0.074	28	-0.098	81	109
CAV3	0.04	0.008	-10000	0	0	21	21
CAV1	0.036	0.015	-10000	0	0	80	80
SHC/Grb2/SOS1	0.05	0.084	-10000	0	-0.12	94	94
PDGF/PDGFRA/Shf	0.011	0.071	-10000	0	-0.14	83	83
FOS	-0.12	0.26	0.32	1	-0.65	99	100
JUN	-0.034	0.042	0.23	3	-0.2	10	13
oligodendrocyte development	-0.008	0.091	-10000	0	-0.16	127	127
GRB2	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:DAG	-0.016	0.046	0.074	28	-0.098	81	109
PDGF/PDGFRA	0.017	0.035	-10000	0	-0.055	77	77
actin cytoskeleton reorganization	0.013	0.072	-10000	0	-0.14	84	84
SRF	-0.007	0.024	0.033	126	-10000	0	126
SHC1	0.04	0.009	-10000	0	0	29	29
PI3K	0.011	0.081	-10000	0	-0.14	93	93
PDGF/PDGFRA/Crk/C3G	0.034	0.072	-10000	0	-0.12	84	84
JAK1	-0.011	0.02	0.027	34	-10000	0	34
ELK1/SRF	-0.028	0.061	0.15	12	-0.15	57	69
SHB	0.041	0.007	-10000	0	0	16	16
SHF	0.039	0.011	-10000	0	0	41	41
CSNK2A1	0.038	0.03	-10000	0	-0.028	56	56
GO:0007205	-0.025	0.072	0.087	22	-0.2	61	83
SOS1	0.038	0.013	-10000	0	0	57	57
Ras protein signal transduction	0.048	0.082	-10000	0	-0.12	94	94
PDGF/PDGFRA/SHB	0.013	0.072	-10000	0	-0.14	84	84
PDGF/PDGFRA/Caveolin-1	0.01	0.074	-10000	0	-0.15	76	76
ITGAV	0.033	0.017	-10000	0	0	115	115
ELK1	-0.028	0.077	0.19	11	-0.18	66	77
PIK3CA	0.03	0.019	-10000	0	0	150	150
PDGF/PDGFRA/Crk	0.011	0.071	-10000	0	-0.14	84	84
JAK-STAT cascade	-0.011	0.02	0.027	31	-10000	0	31
cell proliferation	0.011	0.071	-10000	0	-0.14	83	83

×

Nongenotropic Androgen 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
PTK2	-0.007	0.005	0	206	-10000	0	206
GNB1/GNG2	0.042	0.07	-10000	0	-0.11	86	86
regulation of S phase of mitotic cell cycle	-0.011	0.076	-10000	0	-0.17	90	90
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.039	0.009	-10000	0	0	29	29
SHBG/T-DHT	0.027	0.006	-10000	0	-10000	0	0
PELP1	0.039	0.009	-10000	0	0	29	29
AKT1	-0.009	0.004	0.002	47	-10000	0	47
MAP2K1	-0.034	0.078	0.17	23	-0.17	82	105
T-DHT/AR	0.006	0.054	-10000	0	-0.13	76	76
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	102	102
GNAI2	0.041	0.006	-10000	0	0	13	13
GNAI3	0.038	0.012	-10000	0	0	46	46
GNAI1	0.035	0.016	-10000	0	0	94	94
mol:GDP	-0.042	0.087	-10000	0	-0.25	69	69
cell proliferation	-0.072	0.17	0.24	6	-0.39	107	113
PIK3CA	0.03	0.019	-10000	0	0	150	150
FOS	-0.12	0.29	0.27	1	-0.7	105	106
mol:Ca2+	-0.006	0.021	-10000	0	-0.049	77	77
MAPK3	-0.054	0.13	0.22	7	-0.3	96	103
MAPK1	-0.041	0.13	-10000	0	-0.3	75	75
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	0	0.002	0.002	78	-0.004	102	180
cAMP biosynthetic process	-0.001	0.024	0.18	5	-10000	0	5
GNG2	0.039	0.01	-10000	0	0	34	34
potassium channel inhibitor activity	0	0.002	0.002	78	-0.004	102	180
HRAS/GTP	0.027	0.077	-10000	0	-0.092	139	139
actin cytoskeleton reorganization	0.029	0.052	-10000	0	-0.11	46	46
SRC	0.039	0.01	-10000	0	0	31	31
voltage-gated calcium channel activity	0	0.002	0.002	78	-0.004	102	180
PI3K	0.023	0.053	-10000	0	-0.12	47	47
apoptosis	0.062	0.18	0.38	113	-0.22	5	118
T-DHT/AR/PELP1	0.026	0.058	-10000	0	-0.11	76	76
HRAS/GDP	-0.006	0.11	0.15	1	-0.23	79	80
CREB1	-0.077	0.18	0.22	5	-0.41	113	118
RAC1-CDC42/GTP	0.038	0.059	-10000	0	-0.11	46	46
AR	0.032	0.017	-10000	0	0	119	119
GNB1	0.041	0.005	-10000	0	0	7	7
RAF1	-0.021	0.075	0.18	25	-0.18	16	41
RAC1-CDC42/GDP	0.016	0.11	0.19	1	-0.23	75	76
T-DHT/AR/PELP1/Src	0.041	0.065	-10000	0	-0.11	73	73
MAP2K2	-0.03	0.073	0.17	19	-0.17	72	91
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.077	-10000	0	-0.17	90	90
GNAZ	0.039	0.011	-10000	0	0	38	38
SHBG	0.04	0.009	-10000	0	0	30	30
Gi family/GNB1/GNG2/GDP	-0.005	0.097	-10000	0	-0.3	33	33
mol:T-DHT	0	0.001	-10000	0	-0.003	25	25
RAC1	0.039	0.01	-10000	0	0	35	35
GNRH1	-0.008	0.004	0	121	-10000	0	121
Gi family/GTP	-0.02	0.076	-10000	0	-0.18	70	70
CDC42	0.04	0.008	-10000	0	0	22	22

×

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	0.038	0.053	-10000	0	-0.14	38	38
ATM	0.036	0.014	-10000	0	0	72	72
UBE2D3	0.038	0.012	-10000	0	0	50	50
PRKDC	0.038	0.011	-10000	0	0	44	44
ATR	0.035	0.016	-10000	0	0	92	92
UBE2L3	0.039	0.01	-10000	0	0	37	37
FANCD2	-0.004	0.089	-10000	0	-0.25	56	56
protein ubiquitination	0.014	0.1	-10000	0	-0.13	152	152
XRCC5	0.039	0.011	-10000	0	0	38	38
XRCC6	0.037	0.014	-10000	0	0	69	69
M/R/N Complex	0.049	0.07	-10000	0	-0.15	48	48
MRE11A	0.038	0.012	-10000	0	0	51	51
DNA-PK	0.053	0.066	-10000	0	-0.14	45	45
FA complex/FANCD2/Ubiquitin	-0.007	0.12	-10000	0	-0.4	33	33
FANCF	0.04	0.009	-10000	0	0	28	28
BRCA1	0.034	0.016	-10000	0	0	99	99
CCNE1	0.028	0.02	-10000	0	0	188	188
CDK2/Cyclin E1	0.011	0.077	-10000	0	-0.14	102	102
FANCG	0.04	0.008	-10000	0	0	21	21
BRCA1/BACH1/BARD1	0.027	0.069	-10000	0	-0.14	73	73
FANCE	0.04	0.008	-10000	0	0	20	20
FANCC	0.04	0.009	-10000	0	0	27	27
NBN	0.035	0.016	-10000	0	0	96	96
FANCA	0.035	0.016	-10000	0	0	94	94
DNA repair	-0.023	0.13	0.26	10	-0.37	38	48
BRCA1/BARD1/ubiquitin	0.027	0.069	-10000	0	-0.14	73	73
BARD1/DNA-PK	0.064	0.082	-10000	0	-0.14	59	59
FANCL	0.038	0.013	-10000	0	0	56	56
mRNA polyadenylation	-0.038	0.053	0.14	38	-10000	0	38
BRCA1/BARD1/CTIP/M/R/N Complex	-0.023	0.14	0.17	3	-0.29	78	81
BRCA1/BACH1/BARD1/TopBP1	0.038	0.077	-10000	0	-0.13	79	79
BRCA1/BARD1/P53	0.004	0.1	-10000	0	-0.13	186	186
BARD1/CSTF1/BRCA1	0.037	0.072	-10000	0	-0.12	74	74
BRCA1/BACH1	0.034	0.016	-10000	0	0	99	99
BARD1	0.037	0.013	-10000	0	0	65	65
PCNA	0.035	0.015	-10000	0	0	88	88
BRCA1/BARD1/UbcH5C	0.041	0.072	-10000	0	-0.12	75	75
BRCA1/BARD1/UbcH7	0.043	0.072	-10000	0	-0.12	74	74
BRCA1/BARD1/RAD51/PCNA	0.034	0.096	-10000	0	-0.13	118	118
BARD1/DNA-PK/P53	0.021	0.12	-10000	0	-0.13	174	174
BRCA1/BARD1/Ubiquitin	0.027	0.069	-10000	0	-0.14	73	73
BRCA1/BARD1/CTIP	0.015	0.087	0.18	11	-0.13	120	131
FA complex	0.011	0.087	-10000	0	-0.28	30	30
BARD1/EWS	0.042	0.05	-10000	0	-0.13	35	35
RBBP8	-0.015	0.009	-10000	0	-10000	0	0
TP53	0.027	0.02	-10000	0	0	200	200
TOPBP1	0.037	0.013	-10000	0	0	58	58
G1/S transition of mitotic cell cycle	-0.002	0.1	0.13	186	-10000	0	186
BRCA1/BARD1	0.019	0.11	-10000	0	-0.13	152	152
CSTF1	0.037	0.014	-10000	0	0	69	69
BARD1/EWS-Fli1	0.019	0.038	-10000	0	-0.13	34	34
CDK2	0.038	0.013	-10000	0	0	56	56
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	38	38
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.069	-10000	0	-0.14	73	73
EWSR1	0.038	0.012	-10000	0	0	51	51

×

Thromboxane A2 receptor 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
TGM2	0.034	0.016	-10000	0	0	101	101
GNB1/GNG2	-0.064	0.086	-10000	0	-0.18	188	188
AKT1	-0.027	0.14	0.25	2	-0.29	26	28
EGF	0.038	0.012	-10000	0	0	52	52
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.005	0.06	0.2	12	-0.18	2	14
mol:Ca2+	-0.053	0.19	0.29	3	-0.3	165	168
LYN	0.002	0.057	0.2	12	-0.17	4	16
RhoA/GTP	-0.02	0.088	0.14	6	-0.13	173	179
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.073	0.21	0.32	2	-0.34	186	188
GNG2	0.039	0.01	-10000	0	0	34	34
ARRB2	0.039	0.01	-10000	0	0	37	37
TP alpha/Gq family/GDP/G beta5/gamma2	-0.025	0.16	-10000	0	-0.52	46	46
G beta5/gamma2	-0.074	0.12	-10000	0	-0.24	184	184
PRKCH	-0.073	0.22	0.33	1	-0.35	185	186
DNM1	0.039	0.01	-10000	0	0	36	36
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	-0.068	0.18	-10000	0	-0.3	186	186
ADRBK1	0.041	0.005	-10000	0	0	7	7
ADRBK2	0.036	0.015	-10000	0	0	80	80
RhoA/GTP/ROCK1	0.051	0.024	-10000	0	-0.11	9	9
mol:GDP	0.03	0.16	0.45	42	-0.23	1	43
mol:NADP	0.038	0.012	-10000	0	0	46	46
RAB11A	0.04	0.009	-10000	0	0	24	24
PRKG1	0.04	0.009	-10000	0	0	30	30
mol:IP3	-0.076	0.23	0.35	1	-0.38	168	169
cell morphogenesis	0.05	0.024	-10000	0	-0.11	9	9
PLCB2	-0.12	0.3	-10000	0	-0.51	168	168
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.002	0.054	0.22	7	-0.18	2	9
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.003	0.057	0.24	6	-0.18	3	9
RHOA	0.041	0.007	-10000	0	0	14	14
PTGIR	0.04	0.009	-10000	0	0	28	28
PRKCB1	-0.079	0.23	0.34	1	-0.38	183	184
GNAQ	0.038	0.012	-10000	0	0	50	50
mol:L-citrulline	0.038	0.012	-10000	0	0	46	46
TXA2/TXA2-R family	-0.12	0.3	0.38	1	-0.52	189	190
LCK	0.004	0.059	0.21	11	-0.18	2	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.053	0.049	0.23	3	-0.16	5	8
TXA2-R family/G12 family/GDP/G beta/gamma	0.014	0.11	-10000	0	-0.41	32	32
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.049	0.05	0.23	3	-0.15	7	10
MAPK14	-0.041	0.15	0.24	6	-0.23	173	179
TGM2/GTP	-0.087	0.25	0.4	1	-0.42	155	156
MAPK11	-0.048	0.14	0.25	3	-0.23	170	173
ARHGEF1	-0.031	0.12	0.2	10	-0.18	177	187
GNAI2	0.041	0.006	-10000	0	0	13	13
JNK cascade	-0.079	0.24	0.33	2	-0.38	189	191
RAB11/GDP	0.04	0.009	-10000	0	0	24	24
ICAM1	-0.059	0.2	0.27	6	-0.32	180	186
cAMP biosynthetic process	-0.072	0.21	0.33	1	-0.35	155	156
Gq family/GTP/EBP50	0.01	0.049	0.25	2	-0.14	43	45
actin cytoskeleton reorganization	0.05	0.024	-10000	0	-0.11	9	9
SRC	0.003	0.059	0.2	11	-0.18	2	13
GNB5	0.04	0.009	-10000	0	0	28	28
GNB1	0.041	0.005	-10000	0	0	7	7
EGF/EGFR	0.003	0.076	0.22	11	-0.21	12	23
VCAM1	-0.063	0.21	0.28	4	-0.33	187	191
TP beta/Gq family/GDP/G beta5/gamma2	-0.025	0.16	-10000	0	-0.52	46	46
platelet activation	-0.058	0.19	0.32	2	-0.3	176	178
PGI2/IP	0.028	0.016	-10000	0	-0.13	5	5
PRKACA	0.019	0.022	-10000	0	-0.16	6	6
Gq family/GDP/G beta5/gamma2	-0.017	0.13	-10000	0	-0.44	40	40
TXA2/TP beta/beta Arrestin2	0.016	0.058	-10000	0	-0.32	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.003	0.023	0.11	5	-0.16	6	11
mol:DAG	-0.091	0.26	0.36	1	-0.42	184	185
EGFR	0.036	0.014	-10000	0	0	73	73
TXA2/TP alpha	-0.1	0.28	0.38	1	-0.47	161	162
Gq family/GTP	-0.009	0.066	-10000	0	-0.18	63	63
YES1	0.002	0.057	0.22	8	-0.18	2	10
GNAI2/GTP	0.027	0.045	-10000	0	-0.14	9	9
PGD2/DP	0.03	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.038	0.012	-10000	0	0	47	47
FYN	0.002	0.058	0.2	11	-0.17	4	15
mol:NO	0.038	0.012	-10000	0	0	46	46
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	0.062	0.063	0.25	2	-0.21	4	6
NOS3	0.038	0.012	-10000	0	0	46	46
RAC1	0.039	0.01	-10000	0	0	35	35
PRKCA	-0.073	0.22	0.33	4	-0.36	179	183
PRKCB	-0.071	0.22	0.31	1	-0.35	188	189
PRKCE	-0.072	0.22	0.32	5	-0.36	175	180
PRKCD	-0.082	0.23	0.33	1	-0.38	186	187
PRKCG	-0.081	0.24	0.34	1	-0.38	187	188
muscle contraction	-0.11	0.28	0.38	1	-0.47	190	191
PRKCZ	-0.071	0.21	0.3	2	-0.34	189	191
ARR3	0.042	0.002	-10000	0	0	1	1
TXA2/TP beta	0.045	0.051	0.24	1	-0.15	6	7
PRKCQ	-0.073	0.22	0.36	3	-0.36	179	182
MAPKKK cascade	-0.1	0.27	0.36	1	-0.44	180	181
SELE	-0.052	0.18	0.28	3	-0.29	188	191
TP beta/GNAI2/GDP/G beta/gamma	0.072	0.059	0.25	2	-0.19	4	6
ROCK1	0.04	0.007	-10000	0	0	18	18
GNA14	0.039	0.01	-10000	0	0	33	33
chemotaxis	-0.15	0.34	-10000	0	-0.6	189	189
GNA12	0.039	0.01	-10000	0	0	36	36
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	63	63
Rac1/GTP	0.028	0.01	-10000	0	-0.13	1	1

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.03	0.019	-10000	0	0	162	162
HRAS	0.04	0.009	-10000	0	0	29	29
EGFR	0.036	0.014	-10000	0	0	73	73
AKT	0.016	0.093	0.22	7	-0.19	38	45
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.039	0.011	-10000	0	0	38	38
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.03	0.019	-10000	0	0	156	156
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.027	0.02	-10000	0	0	195	195
PIK3CA	0.03	0.019	-10000	0	0	150	150
PIK3CB	0.034	0.016	-10000	0	0	99	99
NRAS	0.039	0.01	-10000	0	0	31	31
PIK3CG	0.033	0.017	-10000	0	0	120	120
PIK3R3	0.034	0.016	-10000	0	0	97	97
PIK3R2	0.037	0.013	-10000	0	0	64	64
NF1	0.034	0.016	-10000	0	0	98	98
RAS	0.004	0.078	0.15	33	-0.24	20	53
ERBB2	0.038	0.012	-10000	0	0	49	49
proliferation/survival/translation	-0.016	0.087	0.22	33	-0.22	16	49
PI3K	0.002	0.09	0.18	18	-0.22	45	63
PIK3R1	0.034	0.016	-10000	0	0	106	106
KRAS	0.034	0.016	-10000	0	0	103	103
FOXO	0.037	0.054	0.17	21	-10000	0	21
AKT2	0.038	0.011	-10000	0	0	45	45
PTEN	0.039	0.011	-10000	0	0	39	39

×

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	122	122
IHH	0.022	0.066	-10000	0	-0.099	125	125
SHH Np/Cholesterol/GAS1	0.028	0.025	-10000	0	-0.1	12	12
LRPAP1	0.036	0.015	-10000	0	0	79	79
dorsoventral neural tube patterning	-0.028	0.025	0.1	12	-10000	0	12
SMO/beta Arrestin2	0.018	0.12	0.24	2	-0.2	106	108
SMO	-0.003	0.11	-10000	0	-0.2	112	112
AKT1	-0.013	0.13	-10000	0	-0.4	35	35
ARRB2	0.039	0.01	-10000	0	0	37	37
BOC	0.035	0.015	-10000	0	0	86	86
ADRBK1	0.041	0.005	-10000	0	0	7	7
heart looping	-0.002	0.11	0.19	3	-0.2	112	115
STIL	0	0.096	0.21	28	-0.17	104	132
DHH N/PTCH2	0.058	0.016	-10000	0	-10000	0	0
DHH N/PTCH1	0.004	0.11	-10000	0	-0.19	125	125
PIK3CA	0.03	0.019	-10000	0	0	150	150
DHH	0.041	0.007	-10000	0	0	14	14
PTHLH	-0.033	0.17	-10000	0	-0.38	106	106
determination of left/right symmetry	-0.002	0.11	0.19	3	-0.2	112	115
PIK3R1	0.034	0.016	-10000	0	0	106	106
skeletal system development	-0.032	0.17	-10000	0	-0.38	106	106
IHH N/Hhip	0.035	0.054	-10000	0	-0.06	117	117
DHH N/Hhip	0.054	0.022	-10000	0	-0.14	1	1
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.002	0.11	0.19	3	-0.2	112	115
pancreas development	0.038	0.013	-10000	0	0	55	55
HHAT	0.04	0.008	-10000	0	0	20	20
PI3K	0.024	0.062	-10000	0	-0.15	47	47
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.037	0.013	-10000	0	0	65	65
somite specification	-0.002	0.11	0.19	3	-0.2	112	115
SHH Np/Cholesterol/PTCH1	-0.006	0.085	-10000	0	-0.17	108	108
SHH Np/Cholesterol/PTCH2	0.032	0.015	-10000	0	-0.1	1	1
SHH Np/Cholesterol/Megalin	0.021	0.028	-10000	0	-0.1	16	16
SHH	-0.018	0.007	-10000	0	-10000	0	0
catabolic process	-0.036	0.095	-10000	0	-0.21	126	126
SMO/Vitamin D3	-0.007	0.1	0.2	17	-0.2	107	124
SHH Np/Cholesterol/Hhip	0.031	0.017	-10000	0	-0.1	2	2
LRP2	0.03	0.019	-10000	0	0	162	162
receptor-mediated endocytosis	0.001	0.1	0.19	20	-0.18	104	124
SHH Np/Cholesterol/BOC	0.026	0.028	-10000	0	-0.1	17	17
SHH Np/Cholesterol/CDO	0.023	0.034	-10000	0	-0.1	28	28
mesenchymal cell differentiation	-0.03	0.017	0.1	2	-10000	0	2
mol:Vitamin D3	-0.013	0.088	0.2	23	-0.17	108	131
IHH N/PTCH2	0.039	0.054	-10000	0	-0.059	116	116
CDON	0.035	0.016	-10000	0	0	91	91
IHH N/PTCH1	-0.02	0.11	-10000	0	-0.21	127	127
Megalin/LRPAP1	0.027	0.055	-10000	0	-0.14	40	40
PTCH2	0.04	0.009	-10000	0	0	26	26
SHH Np/Cholesterol	0.034	0.046	0.2	40	-0.098	1	41
PTCH1	-0.036	0.096	-10000	0	-0.21	126	126
HHIP	0.038	0.013	-10000	0	0	55	55

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.039	0.01	-10000	0	0	35	35
Rac1/GDP	0.032	0.026	-10000	0	-0.024	67	67
DOCK1	0.037	0.013	-10000	0	0	63	63
ITGA4	0.035	0.015	-10000	0	0	90	90
RAC1	0.039	0.01	-10000	0	0	35	35
alpha4/beta7 Integrin	0.032	0.066	-10000	0	-0.14	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.011	-10000	0	0	45	45
alpha4/beta1 Integrin	0.046	0.063	-10000	0	-0.12	49	49
alpha4/beta7 Integrin/Paxillin	0.051	0.069	0.18	54	-0.12	50	104
lamellipodium assembly	-0.028	0.15	-10000	0	-0.37	72	72
PIK3CA	0.03	0.019	-10000	0	0	150	150
PI3K	0.024	0.062	-10000	0	-0.15	47	47
ARF6	0.04	0.007	-10000	0	0	18	18
TLN1	0.038	0.012	-10000	0	0	47	47
PXN	-0.017	0.008	-10000	0	-10000	0	0
PIK3R1	0.034	0.016	-10000	0	0	106	106
ARF6/GTP	0.062	0.072	-10000	0	-0.11	51	51
cell adhesion	0.06	0.077	0.2	45	-0.12	58	103
CRKL/CBL	0.055	0.02	-10000	0	-0.14	1	1
alpha4/beta1 Integrin/Paxillin	0.05	0.067	0.18	49	-0.11	48	97
ITGB1	0.039	0.011	-10000	0	0	39	39
ITGB7	0.039	0.011	-10000	0	0	39	39
ARF6/GDP	0.033	0.025	-10000	0	-0.024	67	67
alpha4/beta1 Integrin/Paxillin/VCAM1	0.024	0.094	0.2	27	-0.13	117	144
p130Cas/Crk/Dock1	0.056	0.053	-10000	0	-0.12	27	27
VCAM1	0.02	0.021	-10000	0	0	287	287
alpha4/beta1 Integrin/Paxillin/Talin	0.063	0.079	0.2	45	-0.12	58	103
alpha4/beta1 Integrin/Paxillin/GIT1	0.068	0.073	0.2	45	-0.11	48	93
BCAR1	0.036	0.014	-10000	0	0	74	74
mol:GDP	-0.065	0.071	0.11	48	-0.2	45	93
CBL	0.04	0.008	-10000	0	0	23	23
PRKACA	0.035	0.015	-10000	0	0	87	87
GIT1	0.04	0.008	-10000	0	0	23	23
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.063	0.079	0.2	45	-0.12	58	103
Rac1/GTP	-0.033	0.17	-10000	0	-0.41	72	72

×

Syndecan-4-mediated signaling events

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
PTK2	-0.059	0.22	-10000	0	-0.35	160	160
Syndecan-4/Syndesmos	-0.04	0.2	-10000	0	-0.43	78	78
positive regulation of JNK cascade	-0.06	0.19	-10000	0	-0.42	85	85
Syndecan-4/ADAM12	-0.057	0.19	-10000	0	-0.47	63	63
CCL5	0.03	0.019	-10000	0	0	162	162
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
DNM2	0.036	0.014	-10000	0	0	72	72
ITGA5	0.037	0.013	-10000	0	0	58	58
SDCBP	0.036	0.014	-10000	0	0	77	77
PLG	0.032	0.029	-10000	0	-0.043	54	54
ADAM12	0.03	0.019	-10000	0	0	159	159
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.039	0.01	-10000	0	0	31	31
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	-0.043	0.19	-10000	0	-0.42	77	77
Syndecan-4/CXCL12/CXCR4	-0.064	0.2	-10000	0	-0.47	74	74
Syndecan-4/Laminin alpha3	-0.05	0.2	-10000	0	-0.48	62	62
MDK	0.04	0.009	-10000	0	0	25	25
Syndecan-4/FZD7	-0.045	0.2	-10000	0	-0.44	77	77
Syndecan-4/Midkine	-0.042	0.2	-10000	0	-0.48	60	60
FZD7	0.037	0.014	-10000	0	0	66	66
Syndecan-4/FGFR1/FGF	-0.029	0.19	-10000	0	-0.45	54	54
THBS1	0.027	0.02	-10000	0	0	198	198
integrin-mediated signaling pathway	-0.059	0.19	-10000	0	-0.43	79	79
positive regulation of MAPKKK cascade	-0.06	0.19	-10000	0	-0.42	85	85
Syndecan-4/TACI	-0.041	0.2	-10000	0	-0.43	78	78
CXCR4	0.033	0.017	-10000	0	0	116	116
cell adhesion	-0.033	0.099	0.21	5	-0.2	127	132
Syndecan-4/Dynamin	-0.039	0.19	-10000	0	-0.47	57	57
Syndecan-4/TSP1	-0.062	0.2	-10000	0	-0.45	75	75
Syndecan-4/GIPC	-0.04	0.19	-10000	0	-0.44	68	68
Syndecan-4/RANTES	-0.054	0.2	-10000	0	-0.47	69	69
ITGB1	0.039	0.011	-10000	0	0	39	39
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	35	35
PRKCA	0.005	0.13	0.86	10	-10000	0	10
Syndecan-4/alpha-Actinin	-0.043	0.2	-10000	0	-0.44	78	78
TFPI	0.039	0.01	-10000	0	0	37	37
F2	0.037	0.026	-10000	0	-0.038	48	48
alpha5/beta1 Integrin	0.045	0.046	-10000	0	-0.14	28	28
positive regulation of cell adhesion	-0.058	0.18	-10000	0	-0.42	75	75
ACTN1	0.039	0.011	-10000	0	0	39	39
TNC	0.027	0.02	-10000	0	0	192	192
Syndecan-4/CXCL12	-0.061	0.2	-10000	0	-0.44	82	82
FGF6	0.037	0.014	-10000	0	0	68	68
RHOA	0.041	0.007	-10000	0	0	14	14
CXCL12	0.029	0.019	-10000	0	0	175	175
TNFRSF13B	0.039	0.011	-10000	0	0	38	38
FGF2	0.038	0.012	-10000	0	0	46	46
FGFR1	0.033	0.017	-10000	0	0	121	121
Syndecan-4/PI-4-5-P2	-0.062	0.18	-10000	0	-0.42	79	79
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.017	0.025	-10000	0	-0.041	26	26
cell migration	-0.011	0.013	-10000	0	-10000	0	0
PRKCD	0.034	0.027	-10000	0	-0.041	43	43
vasculogenesis	-0.059	0.19	-10000	0	-0.43	76	76
SDC4	-0.054	0.19	-10000	0	-0.46	71	71
Syndecan-4/Tenascin C	-0.061	0.2	-10000	0	-0.47	68	68
Syndecan-4/PI-4-5-P2/PKC alpha	-0.019	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.043	0.2	-10000	0	-0.49	56	56
MMP9	0.027	0.024	-10000	0	-0.04	18	18
Rac1/GTP	-0.033	0.1	0.21	5	-0.2	126	131
cytoskeleton organization	-0.038	0.19	-10000	0	-0.41	78	78
GIPC1	0.035	0.015	-10000	0	0	89	89
Syndecan-4/TFPI	-0.043	0.2	-10000	0	-0.43	79	79

×

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	0.014	0.15	-10000	0	-0.36	29	29
MAP3K8	0.04	0.009	-10000	0	0	22	22
FOS	0.014	0.11	-10000	0	-0.36	15	15
PRKCA	0.026	0.029	-10000	0	-0.015	170	170
PTPN7	0.03	0.033	-10000	0	-0.031	115	115
HRAS	0.039	0.009	-10000	0	0	29	29
PRKCB	0	0.007	0.01	94	-0.013	102	196
NRAS	0.039	0.01	-10000	0	0	31	31
RAS family/GTP	0.053	0.05	-10000	0	-0.11	28	28
MAPK3	0.029	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	103	103
BRAF	0	0.073	-10000	0	-0.29	28	28
mol:GTP	0	0.002	0.002	86	-0.004	102	188
MAPK1	0.013	0.11	-10000	0	-0.38	31	31
RAF1	-0.003	0.079	-10000	0	-0.29	36	36
KRAS	0.034	0.016	-10000	0	0	103	103

×

IL23-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
CCL2	-0.17	0.61	-10000	0	-1.2	118	118
IL23A	-0.11	0.55	-10000	0	-1.2	84	84
NF kappa B1 p50/RelA/I kappa B alpha	-0.11	0.54	-10000	0	-1.2	88	88
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	119	119
IL17F	-0.043	0.36	0.49	10	-0.7	89	99
IL12B	0.034	0.073	0.16	9	-0.081	1	10
STAT1 (dimer)	-0.15	0.58	-10000	0	-1.3	89	89
CD4	-0.11	0.57	0.71	2	-1.2	97	99
IL23	-0.11	0.52	-10000	0	-1.2	81	81
IL23R	0.037	0.15	-10000	0	-1.2	3	3
IL1B	-0.13	0.59	-10000	0	-1.3	93	93
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.096	0.51	-10000	0	-1.1	82	82
TYK2	0.025	0.055	0.13	1	-10000	0	1
STAT4	0.04	0.009	-10000	0	0	28	28
STAT3	0.038	0.012	-10000	0	0	52	52
IL18RAP	0.041	0.007	-10000	0	-10000	0	0
IL12RB1	0.024	0.057	0.13	1	-10000	0	1
PIK3CA	0.031	0.019	-10000	0	0	150	150
IL12Rbeta1/TYK2	0.038	0.069	-10000	0	-10000	0	0
IL23R/JAK2	0.047	0.17	-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	-0.028	1	1
JAK2	0.031	0.069	0.16	9	-0.081	1	10
PIK3R1	0.034	0.017	-10000	0	0	106	106
NFKB1	0.037	0.016	-10000	0	0	85	85
RELA	0.043	0.008	-10000	0	0	10	10
positive regulation of dendritic cell antigen processing and presentation	-0.096	0.5	-10000	0	-1.1	81	81
ALOX12B	-0.098	0.51	-10000	0	-1.1	82	82
CXCL1	-0.13	0.57	-10000	0	-1.2	108	108
T cell proliferation	-0.13	0.61	0.68	1	-1.3	91	92
NFKBIA	0.038	0.015	-10000	0	0	66	66
IL17A	-0.031	0.29	0.43	10	-0.54	90	100
PI3K	-0.15	0.53	-10000	0	-1.2	88	88
IFNG	0.006	0.04	0.1	4	-0.11	16	20
STAT3 (dimer)	-0.13	0.5	-10000	0	-1.1	87	87
IL18R1	0.041	0.008	-10000	0	-10000	0	0
IL23/IL23R/JAK2/TYK2/SOCS3	-0.013	0.34	0.55	3	-0.66	74	77
IL18/IL18R	0.055	0.066	-10000	0	-0.11	61	61
macrophage activation	-0.007	0.021	0.034	1	-0.044	80	81
TNF	-0.11	0.54	-10000	0	-1.2	82	82
STAT3/STAT4	-0.12	0.55	-10000	0	-1.2	89	89
STAT4 (dimer)	-0.13	0.58	-10000	0	-1.3	90	90
IL18	0.031	0.019	-10000	0	-10000	0	0
IL19	-0.097	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	122	122
MPO	-0.097	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	0.65	-10000	0	-1.4	91	91
IL6	-0.1	0.53	-10000	0	-1.1	89	89
STAT5A	0.038	0.012	-10000	0	0	50	50
IL2	0.039	0.018	-10000	0	-0.033	12	12
positive regulation of tyrosine phosphorylation of STAT protein	-0.002	0.01	-10000	0	-0.028	1	1
CD3E	-0.11	0.55	0.69	1	-1.2	90	91
keratinocyte proliferation	-0.13	0.61	0.68	1	-1.3	91	92
NOS2	-0.098	0.51	0.61	1	-1.1	91	92

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.007	0.11	0.15	55	-0.28	42	97
adherens junction organization	-0.028	0.13	0.17	5	-0.32	62	67
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.011	0.11	0.21	15	-0.27	34	49
FMN1	-0.024	0.12	0.15	3	-0.28	67	70
mol:IP3	0.003	0.099	0.16	60	-0.22	48	108
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.13	0.18	1	-0.29	67	68
CTNNB1	0.041	0.011	0.068	3	0	32	35
AKT1	-0.017	0.091	0.17	5	-0.25	46	51
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.15	-10000	0	-0.36	55	55
CTNND1	0.042	0.009	-10000	0	-0.002	18	18
mol:PI-4-5-P2	-0.022	0.12	0.21	3	-0.28	63	66
VASP	-0.022	0.12	0.16	2	-0.28	64	66
ZYX	-0.017	0.11	0.15	5	-0.29	53	58
JUB	-0.024	0.12	0.15	4	-0.28	64	68
EGFR(dimer)	-0.006	0.13	-10000	0	-0.28	72	72
E-cadherin/beta catenin-gamma catenin	0.049	0.06	-10000	0	-0.11	47	47
mol:PI-3-4-5-P3	-0.005	0.1	0.24	1	-0.26	48	49
PIK3CA	0.03	0.02	-10000	0	-0.001	154	154
PI3K	-0.005	0.11	0.24	1	-0.26	48	49
FYN	-0.013	0.12	0.19	14	-0.27	67	81
mol:Ca2+	0.003	0.098	0.16	60	-0.22	48	108
JUP	0.038	0.014	-10000	0	0	67	67
PIK3R1	0.035	0.018	-10000	0	0	107	107
mol:DAG	0.003	0.099	0.16	60	-0.22	48	108
CDH1	0.035	0.016	-10000	0	0	96	96
RhoA/GDP	0.013	0.12	0.22	15	-0.26	35	50
establishment of polarity of embryonic epithelium	-0.021	0.12	0.23	3	-0.28	62	65
SRC	0.039	0.01	-10000	0	0	31	31
RAC1	0.039	0.01	-10000	0	0	35	35
RHOA	0.041	0.007	-10000	0	0	14	14
EGFR	0.036	0.014	-10000	0	0	73	73
CASR	-0.005	0.093	0.15	58	-0.22	46	104
RhoA/GTP	0.015	0.1	0.2	5	-0.24	36	41
AKT2	-0.018	0.091	0.17	4	-0.25	48	52
actin cable formation	-0.027	0.11	0.2	7	-0.29	60	67
apoptosis	0.002	0.11	0.26	47	-0.16	60	107
CTNNA1	0.04	0.012	-10000	0	-0.001	37	37
mol:GDP	-0.005	0.1	0.16	58	-0.24	47	105
PIP5K1A	-0.023	0.12	0.15	3	-0.28	65	68
PLCG1	0.003	0.1	0.16	60	-0.23	48	108
Rac1/GTP	0.003	0.13	-10000	0	-0.27	68	68
homophilic cell adhesion	0	0.004	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.033	0.017	-10000	0	0	118	118
ANTXR2	0.035	0.016	-10000	0	0	96	96
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.006	0.011	-10000	0	-0.033	73	73
monocyte activation	-0.078	0.17	-10000	0	-0.35	153	153
MAP2K2	-0.042	0.18	-10000	0	-0.58	57	57
MAP2K1	-0.011	0.011	0.007	37	-0.037	69	106
MAP2K7	-0.01	0.011	0.007	36	-0.037	68	104
MAP2K6	-0.009	0.012	0.007	32	-0.039	59	91
CYAA	-0.023	0.033	-10000	0	-0.1	73	73
MAP2K4	-0.01	0.012	0.007	32	-0.039	68	100
IL1B	-0.012	0.042	0.11	10	-0.09	82	92
Channel	0.022	0.056	-10000	0	-0.11	73	73
NLRP1	-0.006	0.01	-10000	0	-0.031	73	73
CALM1	0.04	0.009	-10000	0	0	30	30
negative regulation of phagocytosis	0.003	0.077	-10000	0	-0.43	16	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.006	0.011	0.033	73	-10000	0	73
MAPK3	-0.011	0.011	0.007	36	-0.037	72	108
MAPK1	-0.01	0.011	0.007	35	-0.038	66	101
PGR	-0.008	0.011	0.007	36	-0.037	52	88
PA/Cellular Receptors	0.022	0.062	-10000	0	-0.12	73	73
apoptosis	-0.006	0.011	-10000	0	-0.033	73	73
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.021	0.056	-10000	0	-0.11	74	74
macrophage activation	-0.013	0.021	0.17	3	-0.11	1	4
TNF	0.04	0.009	-10000	0	0	25	25
VCAM1	-0.081	0.17	-10000	0	-0.35	151	151
platelet activation	0.003	0.077	-10000	0	-0.43	16	16
MAPKKK cascade	0.007	0.028	0.084	7	-0.07	22	29
IL18	-0.009	0.042	0.14	4	-0.093	72	76
negative regulation of macrophage activation	-0.006	0.011	-10000	0	-0.033	73	73
LEF	-0.006	0.011	-10000	0	-0.033	73	73
CASP1	0	0.012	0.018	34	-0.03	48	82
mol:cAMP	0	0.077	-10000	0	-0.44	16	16
necrosis	-0.006	0.011	-10000	0	-0.033	73	73
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.022	0.054	-10000	0	-0.1	74	74
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.037	0.013	-10000	0	0	64	64
Jak2/Leptin Receptor	-0.019	0.15	-10000	0	-0.39	56	56
PTP1B/AKT1	-0.036	0.12	-10000	0	-0.24	83	83
FYN	0.034	0.016	-10000	0	0	102	102
p210 bcr-abl/PTP1B	-0.054	0.11	-10000	0	-0.26	88	88
EGFR	0.036	0.017	-10000	0	-0.003	82	82
EGF/EGFR	-0.027	0.12	-10000	0	-0.24	81	81
CSF1	0.035	0.015	-10000	0	0	89	89
AKT1	0.039	0.011	-10000	0	0	38	38
INSR	0.038	0.013	-10000	0	0	53	53
PTP1B/N-cadherin	-0.055	0.12	-10000	0	-0.25	117	117
Insulin Receptor/Insulin	-0.009	0.12	-10000	0	-0.22	62	62
HCK	0.036	0.015	-10000	0	0	79	79
CRK	0.038	0.011	-10000	0	0	45	45
TYK2	-0.038	0.12	0.23	21	-0.26	73	94
EGF	0.036	0.017	-10000	0	-0.007	68	68
YES1	0.037	0.013	-10000	0	0	59	59
CAV1	-0.037	0.11	0.19	1	-0.25	73	74
TXN	0.037	0.012	-10000	0	0	48	48
PTP1B/IRS1/GRB2	-0.029	0.13	-10000	0	-0.26	84	84
cell migration	0.054	0.11	0.26	88	-10000	0	88
STAT3	0.038	0.012	-10000	0	0	52	52
PRLR	0.038	0.017	-10000	0	-10000	0	0
ITGA2B	0.039	0.009	-10000	0	0	29	29
CSF1R	0.035	0.016	-10000	0	0	96	96
Prolactin Receptor/Prolactin	0.055	0.029	-10000	0	-10000	0	0
FGR	0.041	0.007	-10000	0	0	16	16
PTP1B/p130 Cas	-0.038	0.12	-10000	0	-0.25	89	89
Crk/p130 Cas	-0.031	0.13	-10000	0	-0.25	85	85
DOK1	-0.038	0.11	-10000	0	-0.24	70	70
JAK2	-0.032	0.14	-10000	0	-0.4	58	58
Jak2/Leptin Receptor/Leptin	-0.025	0.14	0.26	1	-0.28	70	71
PIK3R1	0.034	0.016	-10000	0	0	106	106
PTPN1	-0.054	0.12	-10000	0	-0.26	91	91
LYN	0.036	0.015	-10000	0	0	83	83
CDH2	0.019	0.021	-10000	0	0	297	297
SRC	0.007	0.089	-10000	0	-0.48	13	13
ITGB3	0.032	0.017	-10000	0	0	120	120
CAT1/PTP1B	-0.038	0.13	0.24	5	-0.29	73	78
CAPN1	0.039	0.009	-10000	0	0	25	25
CSK	0.04	0.008	-10000	0	0	22	22
PI3K	-0.012	0.11	-10000	0	-0.23	49	49
mol:H2O2	0.002	0.005	0.03	1	-10000	0	1
STAT3 (dimer)	-0.022	0.13	0.25	1	-0.26	68	69
negative regulation of transcription	-0.031	0.14	-10000	0	-0.4	58	58
FCGR2A	0.032	0.018	-10000	0	0	126	126
FER	0.037	0.012	-10000	0	0	53	53
alphaIIb/beta3 Integrin	0.038	0.051	-10000	0	-0.14	34	34
BLK	0.033	0.017	-10000	0	0	115	115
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	44	44
BCAR1	0.036	0.014	-10000	0	0	74	74
p210 bcr-abl/Grb2	0.041	0.007	-10000	0	0	14	14
mol:NADPH	-0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.007	0.12	0.22	9	-0.29	48	57
PRL	0.042	0.012	-10000	0	-10000	0	0
SOCS3	-0.024	0.26	-10000	0	-1.1	27	27
SPRY2	0.024	0.021	-10000	0	0	243	243
Insulin Receptor/Insulin/IRS1	0.069	0.038	-10000	0	-0.12	8	8
CSF1/CSF1R	-0.045	0.14	-10000	0	-0.27	90	90
Ras protein signal transduction	0.005	0.066	0.6	5	-10000	0	5
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	-0.042	0.12	-10000	0	-0.27	81	81
STAT5A	-0.044	0.13	-10000	0	-0.27	85	85
GRB2	0.041	0.007	-10000	0	0	14	14
PDGFB-D/PDGFRB	-0.045	0.12	-10000	0	-0.24	97	97
CSN2	0.04	0.069	0.43	2	-10000	0	2
PIK3CA	0.03	0.019	-10000	0	0	150	150
LAT	-0.059	0.19	-10000	0	-0.48	86	86
YBX1	0.048	0.02	-10000	0	-0.28	1	1
LCK	0.04	0.009	-10000	0	0	28	28
SHC1	0.04	0.009	-10000	0	0	29	29
NOX4	0.021	0.021	-10000	0	0	279	279

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.028	0.013	-10000	0	-0.13	3	3
alphaV beta3 Integrin	0.028	0.079	-10000	0	-0.13	90	90
PTK2	-0.012	0.13	0.23	9	-0.28	66	75
IGF1R	0.033	0.017	-10000	0	0	116	116
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.031	0.018	-10000	0	0	139	139
SRC	0.039	0.01	-10000	0	0	31	31
CDKN1B	0.001	0.089	-10000	0	-0.32	34	34
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.014	0.061	-10000	0	-0.26	17	17
ROCK1	0.04	0.007	-10000	0	0	18	18
AKT1	0.006	0.055	0.21	5	-0.25	14	19
PTK2B	-0.013	0.062	0.18	20	-0.18	11	31
alphaV/beta3 Integrin/JAM-A	0.04	0.081	-10000	0	-0.12	87	87
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	90	90
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.056	0.084	-10000	0	-0.12	84	84
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.005	0.083	-10000	0	-0.27	29	29
alphaV/beta3 Integrin/Syndecan-1	0.029	0.079	-10000	0	-0.13	91	91
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.018	0.1	-10000	0	-0.18	71	71
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.03	0.019	-10000	0	0	150	150
alphaV/beta3 Integrin/Osteopontin	0.005	0.099	-10000	0	-0.16	125	125
RPS6KB1	-0.033	0.1	0.26	11	-0.26	16	27
TLN1	0.038	0.012	-10000	0	0	47	47
MAPK3	-0.053	0.16	0.23	1	-0.34	114	115
GPR124	0.037	0.013	-10000	0	0	62	62
MAPK1	-0.05	0.16	0.23	1	-0.34	111	112
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.016	-10000	0	0	106	106
alphaV/beta3 Integrin/Tumstatin	0.031	0.08	-10000	0	-0.13	91	91
cell adhesion	-0.001	0.1	-10000	0	-0.16	130	130
ANGPTL3	0.04	0.009	-10000	0	0	24	24
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	116	116
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
TGFBR2	0.039	0.011	-10000	0	0	38	38
ITGB3	0.033	0.017	-10000	0	0	120	120
IGF1	0.036	0.015	-10000	0	0	82	82
RAC1	0.039	0.01	-10000	0	0	35	35
regulation of cell-matrix adhesion	0.029	0.076	-10000	0	-0.13	82	82
apoptosis	0.033	0.017	-10000	0	0	115	115
CD47	0.037	0.013	-10000	0	0	60	60
alphaV/beta3 Integrin/CD47	0.023	0.087	-10000	0	-0.14	101	101
VCL	0.039	0.01	-10000	0	0	35	35
alphaV/beta3 Integrin/Del1	0.005	0.082	-10000	0	-0.14	110	110
CSF1	0.035	0.015	-10000	0	0	89	89
PIK3C2A	-0.005	0.1	-10000	0	-0.33	46	46
PI4 Kinase/Pyk2	0.005	0.055	-10000	0	-0.11	81	81
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.074	-10000	0	-0.12	92	92
FAK1/Vinculin	0.006	0.12	0.24	11	-0.25	56	67
alphaV beta3/Integrin/ppsTEM5	0.029	0.076	-10000	0	-0.13	82	82
RHOA	0.041	0.007	-10000	0	0	14	14
VTN	0.04	0.008	-10000	0	0	21	21
BCAR1	0.036	0.014	-10000	0	0	74	74
FGF2	0.038	0.012	-10000	0	0	46	46
F11R	-0.018	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.008	0.088	-10000	0	-0.14	121	121
alphaV/beta3 Integrin/TGFBR2	0.027	0.084	-10000	0	-0.14	93	93
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.046	0.09	-10000	0	-0.13	94	94
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.026	0.077	-10000	0	-0.12	98	98
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.021	0.021	-10000	0	0	273	273
alphaV/beta3 Integrin/Pyk2	0.017	0.067	0.21	2	-0.11	86	88
SDC1	0.04	0.009	-10000	0	0	29	29
VAV3	-0.03	0.074	0.19	20	-0.21	37	57
PTPN11	0.04	0.009	-10000	0	0	29	29
IRS1	0.04	0.008	-10000	0	0	22	22
FAK1/Paxillin	0.008	0.12	0.23	11	-0.25	55	66
cell migration	-0.002	0.11	0.21	12	-0.23	57	69
ITGAV	0.033	0.017	-10000	0	0	115	115
PI3K	0.028	0.091	-10000	0	-0.19	31	31
SPP1	0.03	0.019	-10000	0	0	153	153
KDR	0.039	0.01	-10000	0	0	34	34
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.033	0.017	-10000	0	0	115	115
COL4A3	0.041	0.005	-10000	0	0	8	8
angiogenesis	-0.058	0.17	0.26	1	-0.37	114	115
Rac1/GTP	-0.032	0.076	0.19	19	-0.2	34	53
EDIL3	0.027	0.02	-10000	0	0	201	201
cell proliferation	0.026	0.084	-10000	0	-0.14	93	93

×

Signaling events mediated by PRL

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
CCNE1	0.028	0.02	-10000	0	0	188	188
mol:Halofuginone	0.002	0.022	-10000	0	-0.17	9	9
ITGA1	0.032	0.018	-10000	0	0	131	131
CDKN1A	0.02	0.078	-10000	0	-0.36	16	16
PRL-3/alpha Tubulin	0.01	0.038	-10000	0	-0.13	35	35
mol:Ca2+	-0.003	0.071	0.26	34	-10000	0	34
AGT	0.038	0.011	-10000	0	0	44	44
CCNA2	-0.016	0.087	-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	0.026	0.096	-10000	0	-0.35	17	17
MAPK3	-0.012	0.01	0	238	-10000	0	238
PRL-2 /Rab GGTase beta	0.032	0.068	-10000	0	-0.14	70	70
MAPK1	-0.011	0.01	0	252	-10000	0	252
PTP4A1	-0.003	0.076	0.2	4	-0.61	7	11
PTP4A3	0.025	0.021	-10000	0	0	228	228
PTP4A2	0.04	0.009	-10000	0	0	30	30
ITGB1	-0.011	0.01	0	253	-10000	0	253
SRC	0.039	0.01	-10000	0	0	31	31
RAC1	-0.008	0.11	-10000	0	-0.36	44	44
Rab GGTase beta/Rab GGTase alpha	0.035	0.063	-10000	0	-0.14	62	62
PRL-1/ATF-5	0.016	0.095	0.26	2	-0.54	9	11
RABGGTA	0.04	0.009	-10000	0	0	26	26
BCAR1	-0.003	0.069	0.26	32	-10000	0	32
RHOC	-0.006	0.11	-10000	0	-0.36	42	42
RHOA	-0.008	0.11	-10000	0	-0.36	45	45
cell motility	0.01	0.12	0.29	1	-0.34	43	44
PRL-1/alpha Tubulin	-0.018	0.078	-10000	0	-0.54	9	9
PRL-3/alpha1 Integrin	0.009	0.067	-10000	0	-0.15	68	68
ROCK1	0.009	0.12	0.3	1	-0.34	43	44
RABGGTB	0.036	0.015	-10000	0	0	83	83
CDK2	0.038	0.013	-10000	0	0	56	56
mitosis	-0.002	0.076	0.2	6	-0.61	7	13
ATF5	0.038	0.012	-10000	0	0	52	52

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.037	0.014	-10000	0	0	67	67
LAT2	-0.018	0.1	0.19	4	-0.21	86	90
AP1	-0.031	0.18	0.28	1	-0.42	67	68
mol:PIP3	-0.033	0.13	0.26	8	-0.29	77	85
IKBKB	-0.013	0.087	0.2	19	-0.19	56	75
AKT1	0.012	0.12	0.24	60	-0.21	13	73
IKBKG	-0.021	0.082	0.21	6	-0.19	63	69
MS4A2	0.046	0.012	0.071	32	-0.004	10	42
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.03	0.019	-10000	0	0	150	150
MAP3K1	-0.033	0.12	0.22	3	-0.3	68	71
mol:Ca2+	-0.023	0.11	0.22	10	-0.24	66	76
LYN	0.036	0.019	0.09	2	-0.003	92	94
CBLB	-0.014	0.095	0.2	5	-0.21	74	79
SHC1	0.04	0.009	-10000	0	0	29	29
RasGAP/p62DOK	0.021	0.072	-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	-0.011	0.079	0.29	19	-0.16	5	24
PTPN13	-0.057	0.2	-10000	0	-0.66	36	36
PTPN11	0.039	0.02	0.1	2	-0.033	24	26
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.008	0.13	0.3	18	-0.32	31	49
SYK	0.037	0.017	0.09	2	-0.003	74	76
GRB2	0.041	0.007	-10000	0	0	14	14
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.024	0.13	0.18	1	-0.27	97	98
LAT	-0.017	0.095	-10000	0	-0.21	80	80
PAK2	-0.03	0.14	0.22	4	-0.31	73	77
NFATC2	0.004	0.056	-10000	0	-0.41	9	9
HRAS	-0.025	0.14	0.22	4	-0.3	84	88
GAB2	0.031	0.018	-10000	0	0	142	142
PLA2G1B	0.01	0.15	-10000	0	-0.89	14	14
Fc epsilon R1	0.035	0.071	-10000	0	-0.094	111	111
Antigen/IgE/Fc epsilon R1	0.037	0.063	-10000	0	-0.08	103	103
mol:GDP	-0.023	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	106	106
FOS	0.026	0.02	-10000	0	0	205	205
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.009	0.1	-10000	0	-0.21	86	86
CHUK	-0.023	0.083	0.21	6	-0.19	65	71
KLRG1	-0.014	0.079	0.18	4	-0.17	86	90
VAV1	-0.014	0.095	0.18	3	-0.22	73	76
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.017	0.097	0.2	3	-0.21	81	84
negative regulation of mast cell degranulation	-0.02	0.074	0.13	1	-0.18	55	56
BTK	-0.03	0.18	0.26	1	-0.47	55	56
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.027	0.11	-10000	0	-0.22	101	101
GAB2/PI3K/SHP2	-0.04	0.056	-10000	0	-0.15	72	72
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.002	0.066	-10000	0	-0.15	84	84
RAF1	0.013	0.16	-10000	0	-0.98	14	14
Fc epsilon R1/FcgammaRIIB/SHIP	0.033	0.092	-10000	0	-0.12	123	123
FCER1G	0.027	0.02	-10000	0	0	195	195
FCER1A	0.039	0.015	0.1	1	-0.006	45	46
Antigen/IgE/Fc epsilon R1/Fyn	0.041	0.077	-10000	0	-0.093	106	106
MAPK3	0.011	0.15	-10000	0	-0.9	14	14
MAPK1	0.004	0.15	-10000	0	-0.9	14	14
NFKB1	0.035	0.015	-10000	0	0	85	85
MAPK8	-0.033	0.22	-10000	0	-0.56	61	61
DUSP1	0.027	0.02	-10000	0	0	202	202
NF-kappa-B/RelA	0.001	0.068	0.14	12	-0.14	61	73
actin cytoskeleton reorganization	-0.051	0.2	-10000	0	-0.72	31	31
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.016	0.13	0.26	3	-0.28	77	80
FER	-0.015	0.093	-10000	0	-0.21	74	74
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	57	57
PLCG1	-0.028	0.15	0.28	3	-0.35	72	75
cytokine secretion	-0.003	0.047	0.086	10	-0.098	65	75
SPHK1	-0.017	0.098	0.21	3	-0.21	83	86
PTK2	-0.055	0.22	-10000	0	-0.78	31	31
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.018	0.14	-10000	0	-0.27	99	99
EDG1	-0.01	0.002	-10000	0	-10000	0	0
mol:DAG	-0.036	0.13	0.25	8	-0.3	78	86
MAP2K2	0.003	0.15	-10000	0	-0.91	14	14
MAP2K1	0.004	0.15	-10000	0	-0.91	14	14
MAP2K7	0.038	0.011	-10000	0	0	44	44
KLRG1/SHP2	0.013	0.091	0.2	35	-0.21	36	71
MAP2K4	-0.073	0.32	-10000	0	-0.89	74	74
Fc epsilon R1/FcgammaRIIB	0.036	0.099	-10000	0	-0.13	123	123
mol:Choline	-0.011	0.079	0.29	19	-0.16	5	24
SHC/Grb2/SOS1	0.023	0.13	-10000	0	-0.21	85	85
FYN	0.034	0.016	-10000	0	0	102	102
DOK1	0.04	0.009	-10000	0	0	24	24
PXN	-0.054	0.2	-10000	0	-0.71	30	30
HCLS1	-0.01	0.098	0.2	6	-0.24	59	65
PRKCB	-0.025	0.1	0.22	8	-0.23	77	85
FCGR2B	0.03	0.019	-10000	0	0	158	158
IGHE	0	0.006	0.048	2	-10000	0	2
KLRG1/SHIP	-0.02	0.075	0.13	1	-0.19	55	56
LCP2	0.034	0.016	-10000	0	0	100	100
PLA2G4A	-0.006	0.092	0.17	12	-0.22	62	74
RASA1	0.036	0.014	-10000	0	0	73	73
mol:Phosphatidic acid	-0.011	0.079	0.29	19	-0.16	5	24
IKK complex	-0.016	0.072	0.21	9	-0.17	38	47
WIPF1	0	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.037	0.013	-10000	0	0	63	63
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.034	0.13	-10000	0	-0.3	87	87
IRAK/TOLLIP	0.04	0.027	0.19	4	-0.1	11	15
IKBKB	0.038	0.011	-10000	0	0	44	44
IKBKG	0.042	0.003	-10000	0	0	2	2
IL1 alpha/IL1R2	0.046	0.039	-10000	0	-0.14	16	16
IL1A	0.039	0.01	-10000	0	0	31	31
IL1B	-0.012	0.01	-10000	0	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0.046	0.078	0.22	2	-0.12	63	65
IL1R2	0.036	0.015	-10000	0	0	82	82
IL1R1	0.031	0.018	-10000	0	0	142	142
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.044	0.14	-10000	0	-0.35	71	71
TOLLIP	0.04	0.009	-10000	0	0	28	28
TICAM2	0.038	0.013	-10000	0	0	57	57
MAP3K3	0.04	0.008	-10000	0	0	19	19
TAK1/TAB1/TAB2	0.06	0.056	-10000	0	-0.14	26	26
IKK complex/ELKS	0.013	0.088	0.25	3	-0.28	24	27
JUN	-0.034	0.06	0.15	25	-0.2	17	42
MAP3K7	0.038	0.012	-10000	0	0	47	47
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0	0.12	0.22	2	-0.17	126	128
IL1 alpha/IL1R1/IL1RAP/MYD88	0.038	0.085	-10000	0	-0.12	92	92
PIK3R1	0.034	0.016	-10000	0	0	106	106
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.039	0.099	-10000	0	-0.13	101	101
IL1 beta fragment/IL1R1/IL1RAP	-0.011	0.096	0.18	6	-0.15	140	146
NFKB1	0.035	0.015	-10000	0	0	85	85
MAPK8	-0.025	0.057	0.17	23	-0.2	16	39
IRAK1	0.016	0.014	-10000	0	-0.11	6	6
IL1RN/IL1R1	0.023	0.07	-10000	0	-0.14	79	79
IRAK4	0.037	0.014	-10000	0	0	70	70
PRKCI	0.027	0.02	-10000	0	0	193	193
TRAF6	0.04	0.009	-10000	0	0	24	24
PI3K	0.024	0.062	-10000	0	-0.15	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.035	0.15	0.17	2	-0.31	96	98
CHUK	0.038	0.012	-10000	0	0	52	52
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.011	0.096	0.18	6	-0.15	140	146
IL1 beta/IL1R2	-0.003	0.089	0.24	3	-0.15	130	133
IRAK/TRAF6/TAK1/TAB1/TAB2	0.07	0.07	0.22	1	-0.14	32	33
NF kappa B1 p50/RelA	-0.014	0.11	-10000	0	-0.23	73	73
IRAK3	0.034	0.016	-10000	0	0	97	97
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.004	0.12	0.22	2	-0.22	67	69
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.014	0.098	-10000	0	-0.19	101	101
IL1 alpha/IL1R1/IL1RAP	0.016	0.077	-10000	0	-0.13	92	92
RELA	0.041	0.006	-10000	0	0	10	10
MAP3K7IP1	0.038	0.012	-10000	0	0	51	51
SQSTM1	0.038	0.012	-10000	0	0	48	48
MYD88	0.041	0.007	-10000	0	0	15	15
IRAK/TRAF6/MEKK3	0.06	0.038	0.2	4	-0.11	18	22
IL1RAP	0.027	0.02	-10000	0	0	192	192
UBE2N	0.04	0.008	-10000	0	0	19	19
IRAK/TRAF6	-0.021	0.095	-10000	0	-0.21	68	68
CASP1	0.028	0.02	-10000	0	0	187	187
IL1RN/IL1R2	0.042	0.049	-10000	0	-0.14	30	30
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.003	0.1	0.2	6	-0.15	134	140
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.02	0.13	0.21	1	-0.29	81	82
PIK3CA	0.03	0.019	-10000	0	0	150	150
IL1RN	0.039	0.01	-10000	0	0	37	37
TRAF6/TAK1/TAB1/TAB2	0.071	0.068	-10000	0	-0.14	31	31
MAP2K6	-0.021	0.06	0.19	23	-0.21	13	36

×

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

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
MET/RANBP9	0.01	0.076	-10000	0	-0.14	103	103
CRKL	-0.032	0.14	0.33	1	-0.42	42	43
mol:PIP3	0.009	0.081	0.29	2	-0.82	4	6
AKT1	0.003	0.085	0.38	4	-0.73	4	8
PTK2B	0.033	0.017	-10000	0	0	116	116
RAPGEF1	-0.035	0.13	0.31	1	-0.41	40	41
RANBP10	0.036	0.014	-10000	0	0	77	77
PIK3CA	0.03	0.019	-10000	0	0	150	150
HGF/MET/SHIP2	0.029	0.078	-10000	0	-0.12	101	101
MAP3K5	-0.024	0.14	0.28	2	-0.4	41	43
HGF/MET/CIN85/CBL/ENDOPHILINS	0.05	0.085	-10000	0	-0.11	104	104
AP1	-0.004	0.082	0.16	10	-0.12	142	152
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.04	0.009	-10000	0	0	29	29
apoptosis	-0.16	0.35	-10000	0	-0.77	135	135
STAT3 (dimer)	-0.011	0.11	0.19	4	-0.29	39	43
GAB1/CRKL/SHP2/PI3K	-0.012	0.15	-10000	0	-0.39	43	43
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.01	0.15	0.29	3	-0.4	42	45
PTPN11	0.04	0.009	-10000	0	0	29	29
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.039	0.011	-10000	0	0	39	39
PTEN	0.039	0.011	-10000	0	0	39	39
ELK1	0.013	0.12	0.32	51	-10000	0	51
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.013	0.085	0.17	2	-0.22	46	48
PAK1	0.01	0.1	0.36	10	-0.69	4	14
HGF/MET/RANBP10	0.024	0.076	-10000	0	-0.11	103	103
HRAS	-0.071	0.22	-10000	0	-0.48	118	118
DOCK1	-0.031	0.14	0.31	2	-0.41	40	42
GAB1	-0.029	0.15	0.25	1	-0.44	40	41
CRK	-0.028	0.14	0.28	3	-0.41	42	45
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.057	0.19	-10000	0	-0.42	112	112
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	0.016	-10000	0	0	106	106
cell morphogenesis	-0.011	0.15	0.26	36	-0.35	38	74
GRB2/SHC	0.019	0.096	0.19	3	-0.16	106	109
FOS	0.026	0.02	-10000	0	0	205	205
GLMN	0.005	0.007	0.069	6	-10000	0	6
cell motility	0.013	0.12	0.31	51	-10000	0	51
HGF/MET/MUC20	0.014	0.064	-10000	0	-0.11	104	104
cell migration	0.018	0.095	0.19	3	-0.16	106	109
GRB2	0.041	0.007	-10000	0	0	14	14
CBL	0.04	0.008	-10000	0	0	23	23
MET/RANBP10	0.01	0.073	-10000	0	-0.13	104	104
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.017	0.081	-10000	0	-0.29	21	21
MET/MUC20	-0.004	0.061	-10000	0	-0.13	106	106
RAP1B	-0.034	0.13	0.27	2	-0.39	36	38
RAP1A	-0.039	0.13	0.3	2	-0.39	41	43
HGF/MET/RANBP9	0.026	0.078	-10000	0	-0.12	101	101
RAF1	-0.072	0.21	-10000	0	-0.46	119	119
STAT3	-0.01	0.11	0.19	4	-0.3	35	39
cell proliferation	-0.031	0.14	0.26	10	-0.3	81	91
RPS6KB1	-0.011	0.084	-10000	0	-0.32	29	29
MAPK3	-0.007	0.13	0.66	13	-10000	0	13
MAPK1	0.027	0.2	0.67	41	-10000	0	41
RANBP9	0.038	0.013	-10000	0	0	55	55
MAPK8	-0.021	0.15	-10000	0	-0.41	44	44
SRC	-0.007	0.094	0.2	8	-0.26	30	38
PI3K	-0.001	0.097	0.19	3	-0.18	96	99
MET/Glomulin	0.013	0.046	-10000	0	-0.13	39	39
SOS1	0.038	0.013	-10000	0	0	57	57
MAP2K1	-0.071	0.2	-10000	0	-0.43	118	118
MET	0.027	0.02	-10000	0	0	195	195
MAP4K1	-0.022	0.15	0.29	1	-0.43	39	40
PTK2	0.026	0.02	-10000	0	0	206	206
MAP2K2	-0.072	0.19	-10000	0	-0.43	119	119
BAD	-0.001	0.082	0.34	4	-0.7	4	8
MAP2K4	-0.025	0.13	0.26	2	-0.37	40	42
SHP2/GRB2/SOS1/GAB1	-0.011	0.15	-10000	0	-0.36	51	51
INPPL1	0.04	0.009	-10000	0	0	29	29
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	111	113
PLCgamma1/PKC	0.027	0.021	-10000	0	-0.13	9	9
HGF	0.04	0.009	-10000	0	0	29	29
RASA1	0.036	0.014	-10000	0	0	73	73
NCK1	0.036	0.014	-10000	0	0	77	77
PTPRJ	0.039	0.01	-10000	0	0	36	36
NCK/PLCgamma1	0.014	0.096	0.19	3	-0.16	102	105
PDPK1	0.003	0.079	0.33	2	-0.77	4	6
HGF/MET/SHIP	0.014	0.064	-10000	0	-0.11	104	104

×

Canonical Wnt signaling 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
HDAC1	0.054	0.062	0.15	115	-0.032	31	146
AES	0.052	0.056	0.14	117	-0.032	15	132
FBXW11	0.04	0.008	-10000	0	0	23	23
mol:GTP	0.001	0.003	0.033	1	-10000	0	1
LRP6/FZD1	0.041	0.049	-10000	0	-0.14	31	31
SMAD4	0.038	0.012	-10000	0	0	49	49
DKK2	0.038	0.012	-10000	0	0	49	49
TLE1	0.052	0.052	0.13	111	-0.033	12	123
MACF1	0.033	0.017	-10000	0	0	119	119
CTNNB1	0.034	0.12	0.29	32	-0.4	12	44
WIF1	0.04	0.01	-10000	0	-0.001	32	32
beta catenin/RanBP3	0.097	0.22	0.47	113	-0.41	8	121
KREMEN2	0.04	0.009	-10000	0	0	26	26
DKK1	0.039	0.011	-10000	0	0	41	41
beta catenin/beta TrCP1	0.053	0.12	0.3	29	-0.39	11	40
FZD1	0.041	0.007	-10000	0	0	17	17
AXIN2	-0.045	0.22	0.69	7	-0.87	22	29
AXIN1	0.042	0.004	-10000	0	0	4	4
RAN	0.042	0.007	0.076	1	0	11	12
Axin1/APC/GSK3/beta catenin	0.047	0.088	0.41	1	-0.55	7	8
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.03	0.17	0.33	8	-0.41	62	70
Axin1/APC/GSK3	0.03	0.07	0.2	17	-0.23	13	30
Axin1/APC/GSK3/beta catenin/Macf1	0.021	0.089	0.29	15	-0.25	12	27
HNF1A	0.019	0.05	0.09	132	-10000	0	132
CTBP1	0.052	0.053	0.14	110	-0.033	12	122
MYC	0.055	0.55	0.63	166	-1.1	71	237
RANBP3	0.04	0.012	0.076	1	0	41	42
DKK2/LRP6/Kremen 2	0.057	0.054	-10000	0	-0.12	28	28
NKD1	0.038	0.012	-10000	0	0	50	50
TCF4	0.054	0.059	0.15	113	-0.033	13	126
TCF3	0.051	0.055	0.14	112	-0.034	13	125
WNT1/LRP6/FZD1/Axin1	0.08	0.06	-10000	0	-0.11	30	30
Ran/GTP	0.031	0.013	0.1	1	-0.12	3	4
CtBP/CBP/TCF/TLE1/AES	0.054	0.3	0.62	89	-0.41	21	110
LEF1	0.036	0.05	0.14	72	-0.033	13	85
DVL1	0.032	0.078	0.22	16	-0.28	16	32
CSNK2A1	0.039	0.011	-10000	0	0	40	40
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.067	0.19	-10000	0	-0.42	83	83
DKK1/LRP6/Kremen 2	0.057	0.053	-10000	0	-0.12	27	27
LRP6	0.034	0.016	-10000	0	0	103	103
CSNK1A1	0.059	0.066	0.15	128	-0.032	32	160
NLK	0.032	0.024	-10000	0	-0.04	47	47
CCND1	-0.18	0.5	0.71	17	-1.2	95	112
WNT1	0.041	0.007	-10000	0	0	15	15
GSK3A	0.039	0.011	0.065	1	0	37	38
GSK3B	0.04	0.009	-10000	0	0	29	29
FRAT1	0.039	0.009	-10000	0	-0.002	26	26
PPP2R5D	0.034	0.064	0.24	2	-0.28	13	15
APC	-0.005	0.083	0.21	61	-10000	0	61
WNT1/LRP6/FZD1	0.019	0.062	0.19	4	-0.23	8	12
CREBBP	0.054	0.054	0.14	115	-0.033	15	130

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.087	0.34	-10000	0	-0.8	81	81
CRP	-0.081	0.33	0.49	2	-0.76	80	82
cell cycle arrest	-0.12	0.39	-10000	0	-0.86	94	94
TIMP1	-0.1	0.36	-10000	0	-0.74	115	115
IL6ST	0.024	0.036	-10000	0	-0.041	84	84
Rac1/GDP	-0.012	0.17	0.29	5	-0.36	68	73
AP1	-0.03	0.21	-10000	0	-0.46	79	79
GAB2	0.032	0.021	-10000	0	-0.04	2	2
TNFSF11	-0.085	0.33	-10000	0	-0.76	81	81
HSP90B1	0.013	0.092	-10000	0	-1.1	2	2
GAB1	0.039	0.014	-10000	0	-0.037	2	2
MAPK14	-0.027	0.17	0.26	1	-0.55	36	37
AKT1	-0.012	0.16	0.29	3	-0.46	35	38
FOXO1	-0.012	0.15	0.28	3	-0.44	35	38
MAP2K6	-0.021	0.15	0.23	3	-0.39	56	59
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.033	0.21	0.3	8	-0.42	87	95
MITF	-0.018	0.15	0.23	6	-0.33	68	74
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.037	0.014	-10000	0	0	67	67
A2M	-0.12	0.41	-10000	0	-1.2	67	67
CEBPB	0.037	0.014	-10000	0	0	73	73
GRB2/SOS1/GAB family/SHP2	-0.01	0.16	0.31	5	-0.4	56	61
STAT3	-0.14	0.42	-10000	0	-0.95	94	94
STAT1	-0.071	0.28	-10000	0	-0.83	64	64
CEBPD	-0.084	0.34	0.5	3	-0.78	80	83
PIK3CA	0.031	0.02	-10000	0	-0.047	2	2
PI3K	0.024	0.062	-10000	0	-0.15	49	49
JUN	0.036	0.015	-10000	0	0	80	80
PIAS3/MITF	-0.008	0.15	-10000	0	-0.34	61	61
MAPK11	-0.026	0.16	0.26	1	-0.57	34	35
STAT3 (dimer)/FOXO1	-0.098	0.35	0.48	2	-0.73	102	104
GRB2/SOS1/GAB family	0.03	0.13	0.3	6	-0.29	32	38
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.007	0.11	0.19	3	-0.26	56	59
GRB2	0.042	0.009	-10000	0	-0.005	16	16
JAK2	0.034	0.017	-10000	0	0	108	108
LBP	-0.032	0.26	0.44	1	-0.57	74	75
PIK3R1	0.034	0.018	-10000	0	-0.043	3	3
JAK1	0.033	0.029	-10000	0	-0.045	54	54
MYC	-0.065	0.42	0.52	6	-0.87	98	104
FGG	-0.085	0.33	-10000	0	-0.76	80	80
macrophage differentiation	-0.12	0.39	-10000	0	-0.86	94	94
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.047	0.1	-10000	0	-0.17	50	50
JUNB	-0.1	0.39	0.5	4	-0.85	99	103
FOS	0.026	0.02	-10000	0	0	205	205
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.16	0.25	2	-0.35	69	71
STAT1/PIAS1	-0.021	0.18	0.29	2	-0.37	81	83
GRB2/SOS1/GAB family/SHP2/PI3K	-0.012	0.16	-10000	0	-0.42	46	46
STAT3 (dimer)	-0.13	0.41	-10000	0	-0.92	94	94
PRKCD	-0.06	0.26	0.33	8	-0.53	101	109
IL6R	0.032	0.028	-10000	0	-0.044	46	46
SOCS3	-0.039	0.22	-10000	0	-0.97	24	24
gp130 (dimer)/JAK1/JAK1/LMO4	0.043	0.089	-10000	0	-0.15	59	59
Rac1/GTP	-0.018	0.18	0.3	5	-0.38	75	80
HCK	0.036	0.015	-10000	0	0	79	79
MAPKKK cascade	-0.026	0.22	-10000	0	-0.5	79	79
bone resorption	-0.077	0.31	-10000	0	-0.71	82	82
IRF1	-0.14	0.42	-10000	0	-0.93	108	108
mol:GDP	-0.021	0.15	0.24	5	-0.35	66	71
SOS1	0.039	0.015	-10000	0	-0.036	2	2
VAV1	-0.022	0.15	0.23	4	-0.35	66	70
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.016	0.18	-10000	0	-0.56	40	40
PTPN11	-0.001	0.17	-10000	0	-0.79	22	22
IL6/IL6RA	0.028	0.064	-10000	0	-0.14	43	43
gp130 (dimer)/TYK2/TYK2/LMO4	0.049	0.066	-10000	0	-0.12	43	43
gp130 (dimer)/JAK2/JAK2/LMO4	0.04	0.076	-10000	0	-0.12	70	70
IL6	0.023	0.037	-10000	0	-0.041	100	100
PIAS3	0.04	0.008	-10000	0	0	23	23
PTPRE	0.027	0.038	0.098	15	-0.049	35	50
PIAS1	0.04	0.009	-10000	0	0	28	28
RAC1	0.039	0.01	-10000	0	0	35	35
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.002	0.093	-10000	0	-0.24	44	44
LMO4	0.028	0.038	-10000	0	-0.04	115	115
STAT3 (dimer)/PIAS3	-0.1	0.4	-10000	0	-0.87	92	92
MCL1	-0.011	0.16	-10000	0	-0.73	13	13

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.037	0.014	-10000	0	0	70	70
GNB1/GNG2	0.013	0.12	0.23	2	-0.26	46	48
mol:DAG	-0.007	0.1	0.21	6	-0.25	43	49
PLCG1	-0.008	0.1	0.21	6	-0.26	43	49
YES1	-0.017	0.096	0.2	1	-0.27	44	45
FZD3	0.029	0.019	-10000	0	0	166	166
FZD6	0.029	0.019	-10000	0	0	173	173
G protein	0.029	0.13	0.25	43	-0.26	41	84
MAP3K7	-0.029	0.085	0.17	10	-0.23	41	51
mol:Ca2+	-0.007	0.1	0.2	6	-0.24	43	49
mol:IP3	-0.007	0.1	0.21	6	-0.25	43	49
NLK	-0.029	0.26	-10000	0	-0.85	49	49
GNB1	0.041	0.005	-10000	0	0	7	7
CAMK2A	-0.018	0.092	0.18	7	-0.24	42	49
MAP3K7IP1	0.038	0.012	-10000	0	0	51	51
Noncanonical Wnts/FZD	-0.019	0.096	-10000	0	-0.2	94	94
CSNK1A1	0.04	0.009	-10000	0	0	24	24
GNAS	-0.011	0.1	0.2	19	-0.28	37	56
GO:0007205	-0.014	0.097	0.19	7	-0.25	45	52
WNT6	0.041	0.006	-10000	0	0	12	12
WNT4	0.04	0.008	-10000	0	0	19	19
NFAT1/CK1 alpha	0.004	0.12	0.3	8	-0.26	45	53
GNG2	0.039	0.01	-10000	0	0	34	34
WNT5A	0.035	0.015	-10000	0	0	90	90
WNT11	0.033	0.017	-10000	0	0	122	122
CDC42	-0.02	0.094	0.19	5	-0.26	43	48

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.031	0.019	-10000	0	0	144	144
ELF1	0.047	0.024	-10000	0	-0.26	2	2
CCNA2	0.032	0.018	-10000	0	0	135	135
PIK3CA	0.031	0.019	-10000	0	0	150	150
JAK3	0.038	0.013	-10000	0	-0.001	57	57
PIK3R1	0.034	0.017	-10000	0	-0.001	108	108
JAK1	0.039	0.011	-10000	0	-0.002	38	38
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.001	0.14	-10000	0	-0.33	46	46
SHC1	0.04	0.01	-10000	0	-0.001	30	30
SP1	0.044	0.043	-10000	0	-0.27	9	9
IL2RA	0.019	0.032	-10000	0	-0.49	2	2
IL2RB	0.037	0.015	-10000	0	-0.001	72	72
SOS1	0.038	0.014	-10000	0	-0.001	59	59
IL2RG	0.028	0.02	-10000	0	0	182	182
G1/S transition of mitotic cell cycle	-0.042	0.18	0.3	3	-0.62	26	29
PTPN11	0.04	0.011	-10000	0	-0.004	33	33
CCND2	0.011	0.062	-10000	0	-0.49	8	8
LCK	0.04	0.011	-10000	0	-0.004	32	32
GRB2	0.041	0.008	-10000	0	-0.004	16	16
IL2	0.038	0.013	-10000	0	-0.002	50	50
CDK6	0.032	0.018	-10000	0	0	128	128
CCND3	0.004	0.14	-10000	0	-0.59	12	12

×

IGF1 pathway

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
NCK2	0.041	0.006	-10000	0	0	10	10
PTK2	0.026	0.02	-10000	0	0	206	206
CRKL	-0.021	0.052	0.12	14	-0.13	67	81
GRB2/SOS1/SHC	0.065	0.05	-10000	0	-0.12	25	25
HRAS	0.04	0.009	-10000	0	0	29	29
IRS1/Crk	0.012	0.056	-10000	0	-0.12	72	72
IGF-1R heterotetramer/IGF1/PTP1B	0.034	0.072	-10000	0	-0.12	72	72
AKT1	0	0.092	0.18	82	-0.18	14	96
BAD	-0.007	0.085	0.16	80	-0.17	14	94
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.02	0.051	0.11	12	-0.13	63	75
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.012	0.069	0.21	6	-0.13	83	89
RAF1	0.014	0.12	0.28	12	-0.47	14	26
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.045	0.087	-10000	0	-0.13	85	85
YWHAZ	0.034	0.016	-10000	0	0	104	104
IGF-1R heterotetramer/IGF1/IRS1	0.019	0.067	0.18	2	-0.13	80	82
PIK3CA	0.03	0.019	-10000	0	0	150	150
RPS6KB1	0.001	0.095	0.18	87	-0.19	19	106
GNB2L1	0.041	0.005	-10000	0	0	7	7
positive regulation of MAPKKK cascade	0.011	0.11	0.26	16	-0.4	11	27
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.016	-10000	0	0	106	106
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
HRAS/GTP	0.014	0.067	-10000	0	-0.13	80	80
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.061	0.09	-10000	0	-0.12	83	83
IGF-1R heterotetramer	0.034	0.024	0.1	2	-0.051	15	17
IGF-1R heterotetramer/IGF1/IRS/Nck	0.038	0.074	0.2	2	-0.13	71	73
Crk/p130 Cas/Paxillin	0.043	0.08	0.25	8	-0.13	67	75
IGF1R	0.034	0.024	0.1	2	-0.051	15	17
IGF1	0.028	0.034	0.1	2	-0.053	65	67
IRS2/Crk	0.01	0.053	0.17	1	-0.13	56	57
PI3K	0.025	0.082	0.21	2	-0.12	85	87
apoptosis	-0.002	0.09	0.17	8	-0.22	30	38
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
PRKCD	-0.009	0.092	0.21	6	-0.21	66	72
RAF1/14-3-3 E	0.032	0.12	0.29	13	-0.42	13	26
BAD/14-3-3	0.002	0.094	0.23	30	-0.18	9	39
PRKCZ	0.002	0.095	0.18	90	-0.18	14	104
Crk/p130 Cas/Paxillin/FAK1	0.009	0.079	0.19	17	-0.16	40	57
PTPN1	0.038	0.012	-10000	0	0	46	46
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.009	0.092	-10000	0	-0.21	71	71
BCAR1	0.036	0.014	-10000	0	0	74	74
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.055	0.077	-10000	0	-0.11	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.038	0.013	-10000	0	0	57	57
IRS1/NCK2	0.026	0.068	0.15	12	-0.13	79	91
GRB10	0.04	0.008	-10000	0	0	23	23
PTPN11	-0.02	0.052	0.12	13	-0.13	64	77
IRS1	0.005	0.062	0.13	19	-0.13	80	99
IRS2	-0.02	0.051	0.12	13	-0.13	64	77
IGF-1R heterotetramer/IGF1	0.021	0.074	0.16	1	-0.16	71	72
GRB2	0.041	0.007	-10000	0	0	14	14
PDPK1	0.009	0.099	0.19	88	-0.18	14	102
YWHAE	0.038	0.012	-10000	0	0	50	50
PRKD1	-0.011	0.095	0.21	7	-0.22	71	78
SHC1	0.04	0.009	-10000	0	0	29	29

×

HIF-2-alpha transcription factor network

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
MMP14	-0.054	0.3	-10000	0	-0.86	64	64
oxygen homeostasis	0.003	0.011	0.033	17	-0.025	3	20
TCEB2	0.04	0.008	-10000	0	0	22	22
TCEB1	0.038	0.012	-10000	0	0	49	49
VHL/Elongin B/Elongin C/HIF2A	0.04	0.13	0.28	10	-0.22	60	70
EPO	0.027	0.18	0.36	10	-0.34	45	55
FIH (dimer)	0.04	0.024	0.088	2	-0.035	35	37
APEX1	0.033	0.033	-10000	0	-0.035	85	85
SERPINE1	-0.008	0.16	0.35	10	-0.32	68	78
FLT1	-0.048	0.26	-10000	0	-0.7	71	71
ADORA2A	0.005	0.17	0.32	24	-0.3	67	91
germ cell development	0.008	0.18	0.34	21	-0.31	77	98
SLC11A2	0.01	0.19	0.34	19	-0.33	72	91
BHLHE40	0.012	0.18	0.32	23	-0.3	72	95
HIF1AN	0.04	0.023	0.088	2	-0.035	34	36
HIF2A/ARNT/SIRT1	0.04	0.16	0.31	12	-0.25	62	74
ETS1	0.043	0.026	0.12	1	-0.11	5	6
CITED2	0.015	0.15	-10000	0	-0.63	24	24
KDR	-0.041	0.26	-10000	0	-0.71	66	66
PGK1	0.012	0.19	0.34	22	-0.34	74	96
SIRT1	0.041	0.008	-10000	0	0	19	19
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.062	0.23	0.46	1	-0.35	64	65
EPAS1	0.005	0.11	0.22	19	-0.22	72	91
SP1	0.034	0.049	-10000	0	-0.11	54	54
ABCG2	0.012	0.18	0.34	18	-0.32	68	86
EFNA1	0.002	0.19	0.34	15	-0.36	72	87
FXN	0.006	0.17	0.32	24	-0.3	68	92
POU5F1	0.006	0.18	0.34	20	-0.32	78	98
neuron apoptosis	-0.061	0.22	0.34	64	-0.46	1	65
EP300	0.036	0.014	-10000	0	0	72	72
EGLN3	0.028	0.027	0.084	1	-0.034	22	23
EGLN2	0.04	0.023	0.09	2	-0.018	58	60
EGLN1	0.039	0.024	0.088	2	-0.035	34	36
VHL/Elongin B/Elongin C	0.069	0.039	-10000	0	-0.12	10	10
VHL	0.04	0.009	-10000	0	0	27	27
ARNT	0.035	0.033	-10000	0	-0.035	84	84
SLC2A1	-0.012	0.18	0.33	13	-0.33	84	97
TWIST1	0.004	0.17	0.32	23	-0.31	66	89
ELK1	0.047	0.013	-10000	0	-0.088	3	3
HIF2A/ARNT/Cbp/p300	0.04	0.16	0.33	11	-0.26	58	69
VEGFA	0.012	0.18	0.32	23	-0.3	72	95
CREBBP	0.038	0.012	-10000	0	0	49	49

×

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.039	0.011	-9999	0	39	39
ITGB7	0.039	0.011	-9999	0	39	39
ITGA4	0.035	0.015	-9999	0	90	90
alpha4/beta7 Integrin	0.032	0.066	-9999	-0.14	65	65
alpha4/beta1 Integrin	0.032	0.065	-9999	-0.14	64	64

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	0.01	0.1	-10000	0	-0.13	142	142
SMAD6-7/SMURF1	0.07	0.039	-10000	0	-0.14	8	8
NOG	0.038	0.012	-10000	0	0	49	49
SMAD9	0.003	0.12	-10000	0	-0.42	39	39
SMAD4	0.038	0.012	-10000	0	0	49	49
SMAD5	-0.006	0.1	0.29	1	-0.28	39	40
BMP7/USAG1	-0.02	0.084	-10000	0	-0.16	132	132
SMAD5/SKI	0.009	0.11	0.29	1	-0.28	41	42
SMAD1	0.002	0.096	-10000	0	-0.3	32	32
BMP2	0.039	0.01	-10000	0	0	32	32
SMAD1/SMAD1/SMAD4	0.026	0.1	-10000	0	-0.3	29	29
BMPR1A	0.037	0.014	-10000	0	0	67	67
BMPR1B	0.031	0.019	-10000	0	0	148	148
BMPR1A-1B/BAMBI	0.007	0.088	-10000	0	-0.14	121	121
AHSG	0.034	0.017	-10000	0	0	108	108
CER1	0.038	0.012	-10000	0	0	47	47
BMP2-4/CER1	0.061	0.044	-10000	0	-0.12	11	11
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.012	0.11	0.19	1	-0.26	58	59
BMP2-4 (homodimer)	0.048	0.035	-10000	0	-0.14	11	11
RGMB	0.039	0.011	-10000	0	0	43	43
BMP6/BMPR2/BMPR1A-1B	0.05	0.085	-10000	0	-0.13	80	80
RGMA	0.039	0.01	-10000	0	0	34	34
SMURF1	0.04	0.008	-10000	0	0	19	19
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0	0.082	0.17	2	-0.24	35	37
BMP2-4/USAG1	0.021	0.071	-10000	0	-0.12	76	76
SMAD6/SMURF1/SMAD5	0.007	0.11	-10000	0	-0.28	41	41
SOSTDC1	0.022	0.021	-10000	0	0	257	257
BMP7/BMPR2/BMPR1A-1B	0.008	0.1	-10000	0	-0.14	153	153
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	9	9
ZFYVE16	0.035	0.016	-10000	0	0	95	95
MAP3K7	0.038	0.012	-10000	0	0	47	47
BMP2-4/CHRD	0.055	0.045	-10000	0	-0.12	8	8
SMAD5/SMAD5/SMAD4	0.006	0.11	0.29	1	-0.28	39	40
MAPK1	0.039	0.011	-10000	0	0	43	43
TAK1/TAB family	0.027	0.12	-10000	0	-0.26	32	32
BMP7 (homodimer)	0.022	0.021	-10000	0	0	267	267
NUP214	0.039	0.01	-10000	0	0	32	32
BMP6/FETUA	0.044	0.028	-10000	0	-10000	0	0
SMAD1/SKI	0.023	0.1	-10000	0	-0.29	32	32
SMAD6	0.039	0.01	-10000	0	0	31	31
CTDSP2	0.039	0.011	-10000	0	0	42	42
BMP2-4/FETUA	0.055	0.045	-10000	0	-0.12	8	8
MAP3K7IP1	0.038	0.012	-10000	0	0	51	51
GREM1	0.034	0.016	-10000	0	0	98	98
BMPR2 (homodimer)	0.039	0.01	-10000	0	0	31	31
GADD34/PP1CA	0.056	0.056	-10000	0	-0.12	35	35
BMPR1A-1B (homodimer)	0.016	0.079	-10000	0	-0.15	90	90
CHRDL1	0.026	0.02	-10000	0	0	209	209
ENDOFIN/SMAD1	0.018	0.1	-10000	0	-0.29	30	30
SMAD6-7/SMURF1/SMAD1	0.048	0.11	-10000	0	-0.3	27	27
SMAD6/SMURF1	0.04	0.008	-10000	0	0	19	19
BAMBI	0.029	0.019	-10000	0	0	173	173
SMURF2	0.039	0.01	-10000	0	0	33	33
BMP2-4/CHRDL1	0.021	0.077	-10000	0	-0.12	100	100
BMP2-4/GREM1	0.054	0.049	-10000	0	-0.12	16	16
SMAD7	0.038	0.012	-10000	0	0	46	46
SMAD8A/SMAD8A/SMAD4	0.017	0.13	-10000	0	-0.4	42	42
SMAD1/SMAD6	0.023	0.1	-10000	0	-0.3	30	30
TAK1/SMAD6	0.051	0.036	-10000	0	-0.14	15	15
BMP7	0.022	0.021	-10000	0	0	267	267
BMP6	0.037	0.013	-10000	0	0	63	63
MAP3K7IP2	0.037	0.013	-10000	0	0	63	63
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.002	0.085	-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	29	29
SMAD7/SMURF1	0.053	0.028	-10000	0	-0.14	7	7
CTDSPL	0.041	0.006	-10000	0	0	12	12
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	41	41
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.001	0.088	0.17	1	-0.25	36	37
CHRD	0.033	0.017	-10000	0	0	113	113
BMPR2	0.039	0.01	-10000	0	0	31	31
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.004	0.088	-10000	0	-0.26	34	34
BMP4	0.036	0.014	-10000	0	0	71	71
FST	0.033	0.017	-10000	0	0	122	122
BMP2-4/NOG	0.06	0.049	-10000	0	-0.12	20	20
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.017	0.11	-10000	0	-0.13	148	148

×

IL4-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
BCL2L1	-0.064	0.5	0.87	1	-1.1	62	63
STAT6 (cleaved dimer)	-0.11	0.46	-10000	0	-0.98	80	80
IGHG1	0.037	0.23	0.46	4	-0.67	8	12
IGHG3	-0.066	0.45	-10000	0	-0.95	74	74
AKT1	-0.053	0.37	-10000	0	-0.83	68	68
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.045	0.36	0.45	1	-0.86	67	68
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.049	0.4	-10000	0	-0.95	63	63
THY1	-0.22	0.66	0.77	1	-1.2	154	155
MYB	0.034	0.016	-10000	0	0	106	106
HMGA1	0.037	0.014	-10000	0	0	69	69
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.024	0.38	0.53	1	-0.77	64	65
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.054	0.4	-10000	0	-0.94	64	64
SP1	0.022	0.073	-10000	0	-0.13	103	103
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.001	0.05	-10000	0	-0.085	3	3
STAT6 (dimer)/ETS1	-0.086	0.47	-10000	0	-0.99	75	75
SOCS1	-0.03	0.35	0.52	1	-0.67	64	65
SOCS3	-0.035	0.37	-10000	0	-0.94	45	45
FCER2	-0.029	0.39	-10000	0	-0.86	38	38
PARP14	0.033	0.019	-10000	0	-10000	0	0
CCL17	-0.059	0.48	-10000	0	-1	61	61
GRB2	0.041	0.007	-10000	0	0	14	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.009	0.3	-10000	0	-0.65	58	58
T cell proliferation	-0.084	0.5	-10000	0	-1	80	80
IL4R/JAK1	-0.077	0.49	-10000	0	-1	77	77
EGR2	-0.056	0.48	-10000	0	-1.1	54	54
JAK2	0.032	0.072	0.17	3	-10000	0	3
JAK3	0.033	0.026	-10000	0	-0.038	43	43
PIK3R1	0.034	0.016	-10000	0	0	106	106
JAK1	0.041	0.041	0.11	4	-0.041	7	11
COL1A2	-0.15	0.56	-10000	0	-1.3	107	107
CCL26	-0.07	0.49	-10000	0	-1	70	70
IL4R	-0.066	0.53	-10000	0	-1.1	75	75
PTPN6	0.006	0.043	-10000	0	-0.08	2	2
IL13RA2	-0.058	0.48	-10000	0	-1.1	58	58
IL13RA1	0.037	0.075	0.17	8	-10000	0	8
IRF4	0.059	0.15	-10000	0	-1.3	1	1
ARG1	0.049	0.19	-10000	0	-0.72	5	5
CBL	-0.025	0.35	0.56	2	-0.73	63	65
GTF3A	0.014	0.079	-10000	0	-0.13	119	119
PIK3CA	0.03	0.019	-10000	0	0	150	150
IL13RA1/JAK2	0.042	0.12	0.25	5	-0.18	24	29
IRF4/BCL6	0.043	0.14	-10000	0	-1.2	1	1
CD40LG	0.049	0.01	-10000	0	-0.12	1	1
MAPK14	-0.028	0.36	0.51	1	-0.78	60	61
mitosis	-0.045	0.35	0.49	1	-0.77	68	69
STAT6	-0.063	0.55	0.78	2	-1.1	74	76
SPI1	0.045	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.048	0.34	0.49	1	-0.75	68	69
STAT6 (dimer)	-0.062	0.55	0.78	2	-1.1	74	76
STAT6 (dimer)/PARP14	-0.1	0.49	-10000	0	-1.1	77	77
mast cell activation	-0.005	0.019	-10000	0	-0.041	15	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.074	0.39	-10000	0	-0.92	66	66
FRAP1	-0.053	0.37	-10000	0	-0.83	68	68
LTA	-0.058	0.48	-10000	0	-1.1	54	54
FES	0.04	0.008	-10000	0	0	22	22
T-helper 1 cell differentiation	0.055	0.54	1.1	74	-0.78	2	76
CCL11	-0.09	0.5	-10000	0	-1.1	78	78
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.047	0.39	-10000	0	-0.9	64	64
IL2RG	0.027	0.026	0.094	1	-0.039	22	23
IL10	-0.055	0.48	-10000	0	-1.1	55	55
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.01	-10000	0	0	36	36
IL4	0.041	0.22	-10000	0	-0.93	12	12
IL5	-0.06	0.48	-10000	0	-1	62	62
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.044	0.47	0.69	2	-0.96	65	67
COL1A1	-0.21	0.65	-10000	0	-1.3	137	137
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.083	0.5	-10000	0	-1.1	67	67
IL2R gamma/JAK3	0.019	0.074	-10000	0	-0.13	92	92
TFF3	-0.065	0.5	-10000	0	-1.1	58	58
ALOX15	-0.059	0.48	-10000	0	-1	63	63
MYBL1	0.036	0.014	-10000	0	0	73	73
T-helper 2 cell differentiation	-0.1	0.48	-10000	0	-0.98	81	81
SHC1	0.04	0.009	-10000	0	0	29	29
CEBPB	0.041	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.051	0.4	-10000	0	-0.93	65	65
mol:PI-3-4-5-P3	-0.052	0.37	-10000	0	-0.83	68	68
PI3K	-0.063	0.4	-10000	0	-0.91	68	68
DOK2	0.032	0.018	-10000	0	0	130	130
ETS1	0.001	0.047	-10000	0	-0.098	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.006	0.29	-10000	0	-0.62	60	60
ITGB3	-0.093	0.54	-10000	0	-1.2	74	74
PIGR	-0.056	0.49	-10000	0	-1.1	57	57
IGHE	-0.004	0.088	0.18	40	-0.18	26	66
MAPKKK cascade	-0.005	0.29	-10000	0	-0.61	61	61
BCL6	0.03	0.018	-10000	0	0	141	141
OPRM1	-0.059	0.48	-10000	0	-1	65	65
RETNLB	-0.053	0.48	-10000	0	-1	65	65
SELP	-0.054	0.48	-10000	0	-1	63	63
AICDA	-0.049	0.46	-10000	0	-0.98	64	64

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.039	0.087	0.25	1	-0.14	66	67
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.039	0.01	-10000	0	0	35	35
STAT1 (dimer)/Cbp/p300	0.007	0.12	0.3	5	-0.22	77	82
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.08	-10000	0	-0.15	66	66
antigen processing and presentation of peptide antigen via MHC class I	-0.025	0.093	-10000	0	-0.2	84	84
CaM/Ca2+	0.042	0.088	0.23	1	-0.14	68	69
RAP1A	0.039	0.01	-10000	0	0	35	35
STAT1 (dimer)/SHP2	0.002	0.095	0.21	10	-0.17	79	89
AKT1	0.009	0.11	0.24	33	-0.22	30	63
MAP2K1	-0.024	0.07	0.14	36	-0.17	39	75
MAP3K11	-0.017	0.077	0.19	14	-0.18	27	41
IFNGR1	0.034	0.022	0.079	2	-0.005	112	114
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.011	0.1	-10000	0	-0.29	40	40
Rap1/GTP	-0.043	0.057	0.07	8	-0.18	44	52
CRKL/C3G	0.056	0.018	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.061	0.09	-10000	0	-0.14	60	60
CEBPB	-0.025	0.17	0.28	3	-0.42	58	61
STAT3	0.038	0.012	-10000	0	0	52	52
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.045	0.16	-10000	0	-0.77	16	16
STAT1	-0.024	0.085	0.22	11	-0.21	44	55
CALM1	0.04	0.009	-10000	0	0	30	30
IFN-gamma (dimer)	0.032	0.025	0.082	2	-0.017	102	104
PIK3CA	0.03	0.019	-10000	0	0	150	150
STAT1 (dimer)/PIAS1	-0.007	0.095	0.24	7	-0.2	56	63
CEBPB/PTGES2/Cbp/p300	-0.009	0.12	-10000	0	-0.29	58	58
mol:Ca2+	0.036	0.084	0.23	1	-0.14	66	67
MAPK3	-0.017	0.14	-10000	0	-0.67	13	13
STAT1 (dimer)	-0.022	0.13	0.19	2	-0.28	82	84
MAPK1	-0.05	0.21	0.43	1	-0.73	39	40
JAK2	0.032	0.022	0.076	1	-0.006	128	129
PIK3R1	0.034	0.016	-10000	0	0	106	106
JAK1	0.036	0.023	0.082	1	-0.019	70	71
CAMK2D	0.036	0.015	-10000	0	0	81	81
DAPK1	-0.023	0.16	-10000	0	-0.49	46	46
SMAD7	-0.002	0.072	0.16	32	-0.13	44	76
CBL/CRKL/C3G	0.031	0.088	0.24	8	-0.17	31	39
PI3K	0.021	0.092	0.21	1	-0.18	61	62
IFNG	0.032	0.025	0.082	2	-0.017	103	105
apoptosis	-0.02	0.15	-10000	0	-0.42	54	54
CAMK2G	0.04	0.008	-10000	0	0	23	23
STAT3 (dimer)	0.038	0.012	-10000	0	0	52	52
CAMK2A	0.041	0.006	-10000	0	0	11	11
CAMK2B	0.04	0.007	-10000	0	0	18	18
FRAP1	0	0.1	0.21	38	-0.21	33	71
PRKCD	0.007	0.11	0.24	38	-0.23	31	69
RAP1B	0.038	0.013	-10000	0	0	57	57
negative regulation of cell growth	-0.025	0.093	-10000	0	-0.2	84	84
PTPN2	0.04	0.008	-10000	0	0	23	23
EP300	0.036	0.014	-10000	0	0	72	72
IRF1	-0.043	0.1	0.23	8	-0.26	60	68
STAT1 (dimer)/PIASy	-0.025	0.091	0.22	10	-0.22	36	46
SOCS1	0	0.19	-10000	0	-1.1	16	16
mol:GDP	0.027	0.083	0.22	8	-0.16	33	41
CASP1	-0.021	0.082	0.18	14	-0.17	96	110
PTGES2	0.04	0.009	-10000	0	0	25	25
IRF9	-0.007	0.053	0.12	11	-0.12	56	67
mol:PI-3-4-5-P3	0.007	0.082	-10000	0	-0.17	61	61
RAP1/GDP	0.018	0.087	0.24	1	-0.17	50	51
CBL	-0.015	0.077	0.2	15	-0.18	22	37
MAP3K1	-0.016	0.074	0.16	32	-0.18	28	60
PIAS1	0.04	0.009	-10000	0	0	28	28
PIAS4	0.037	0.013	-10000	0	0	56	56
antigen processing and presentation of peptide antigen via MHC class II	-0.025	0.093	-10000	0	-0.2	84	84
PTPN11	-0.01	0.078	0.17	46	-0.18	24	70
CREBBP	0.038	0.012	-10000	0	0	49	49
RAPGEF1	0.04	0.008	-10000	0	0	22	22

×

FoxO family 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
G6PC	-0.001	0.064	-10000	0	-10000	0	0
PLK1	-0.15	0.38	-10000	0	-0.94	77	77
CDKN1B	-0.043	0.2	0.4	3	-0.38	81	84
FOXO3	-0.14	0.36	-10000	0	-0.6	156	156
KAT2B	-0.008	0.029	0.047	2	-0.047	165	167
FOXO1/SIRT1	0.016	0.077	-10000	0	-0.23	16	16
CAT	-0.16	0.4	0.65	1	-0.94	86	87
CTNNB1	0.039	0.01	-10000	0	0	32	32
AKT1	0.013	0.055	-10000	0	-0.072	81	81
FOXO1	-0.004	0.069	-10000	0	-0.26	9	9
MAPK10	0	0.047	0.19	7	-0.13	20	27
mol:GTP	0	0.003	-10000	0	-10000	0	0
FOXO4	-0.024	0.12	0.24	2	-0.32	49	51
response to oxidative stress	-0.006	0.03	0.061	1	-0.054	95	96
FOXO3A/SIRT1	-0.13	0.35	0.41	1	-0.56	173	174
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	-0.87	7	7
FOXO1/SKP2	0.013	0.073	-10000	0	-0.24	14	14
mol:GDP	-0.006	0.03	0.061	1	-0.054	95	96
RAN	0.041	0.006	-10000	0	0	11	11
GADD45A	-0.075	0.28	-10000	0	-0.75	56	56
YWHAQ	0.04	0.009	-10000	0	0	26	26
FOXO1/14-3-3 family	0.016	0.12	0.24	1	-0.34	35	36
MST1	0.012	0.056	-10000	0	-0.063	183	183
CSNK1D	0.04	0.009	-10000	0	0	30	30
CSNK1E	0.038	0.012	-10000	0	0	54	54
FOXO4/14-3-3 family	0.008	0.13	-10000	0	-0.43	28	28
YWHAB	0.038	0.011	-10000	0	0	44	44
MAPK8	0.001	0.053	0.19	12	-0.13	21	33
MAPK9	0	0.053	0.19	11	-0.15	19	30
YWHAG	0.04	0.009	-10000	0	0	26	26
YWHAE	0.038	0.012	-10000	0	0	50	50
YWHAZ	0.034	0.016	-10000	0	0	104	104
SIRT1	0.037	0.019	0.12	2	-0.035	25	27
SOD2	-0.12	0.3	-10000	0	-0.69	87	87
RBL2	-0.13	0.34	-10000	0	-0.84	68	68
RAL/GDP	0.031	0.056	-10000	0	-0.11	34	34
CHUK	0.012	0.054	-10000	0	-0.064	160	160
Ran/GTP	0.027	0.019	-10000	0	-0.1	4	4
CSNK1G2	0.037	0.014	-10000	0	0	68	68
RAL/GTP	0.031	0.057	-10000	0	-0.1	40	40
CSNK1G1	0.04	0.008	-10000	0	0	21	21
FASLG	0.018	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	49	49
IKBKB	0.011	0.054	-10000	0	-0.064	159	159
CCNB1	-0.18	0.43	-10000	0	-1	89	89
FOXO1-3a-4/beta catenin	-0.057	0.2	-10000	0	-0.4	88	88
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.073	-10000	0	-0.24	14	14
CSNK1A1	0.04	0.009	-10000	0	0	24	24
SGK1	-0.008	0.029	0.047	2	-0.047	165	167
CSNK1G3	0.039	0.01	-10000	0	0	37	37
Ran/GTP/Exportin 1	0.046	0.038	-10000	0	-0.11	25	25
ZFAND5	-0.018	0.1	0.21	4	-0.27	48	52
SFN	0.035	0.015	-10000	0	0	84	84
CDK2	0.04	0.014	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.002	0.14	-10000	0	-0.35	47	47
CREBBP	0.041	0.013	-10000	0	-10000	0	0
FBXO32	-0.19	0.54	0.65	1	-1.1	134	135
BCL6	-0.12	0.35	-10000	0	-0.94	61	61
RALB	0.04	0.009	-10000	0	0	27	27
RALA	0.04	0.01	-10000	0	0	29	29
YWHAH	0.038	0.012	-10000	0	0	54	54

×

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	0.013	0.15	0.25	17	-0.33	59	76
FYN	-0.03	0.18	0.24	15	-0.41	74	89
LAT/GRAP2/SLP76	-0.003	0.15	0.24	6	-0.33	67	73
IKBKB	0.038	0.011	-10000	0	0	44	44
AKT1	-0.015	0.14	0.22	10	-0.31	72	82
B2M	0.037	0.016	-10000	0	-0.002	75	75
IKBKG	-0.002	0.05	0.13	9	-0.11	47	56
MAP3K8	0.04	0.008	-10000	0	0	22	22
mol:Ca2+	-0.014	0.014	0.043	9	-0.043	44	53
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	10	-0.42	72	82
TRPV6	0.081	0.33	1.3	40	-10000	0	40
CD28	0.041	0.007	-10000	0	0	16	16
SHC1	-0.011	0.16	0.22	23	-0.38	60	83
receptor internalization	-0.015	0.14	0.17	3	-0.34	70	73
PRF1	-0.01	0.21	-10000	0	-0.79	26	26
KRAS	0.034	0.016	-10000	0	0	103	103
GRB2	0.041	0.007	-10000	0	0	14	14
COT/AKT1	0.005	0.12	0.22	9	-0.26	69	78
LAT	-0.017	0.16	0.23	10	-0.37	67	77
EntrezGene:6955	0.001	0.003	-10000	0	-0.023	2	2
CD3D	0.035	0.018	-10000	0	-0.001	105	105
CD3E	0.037	0.016	-10000	0	-0.001	81	81
CD3G	0.032	0.02	-10000	0	-0.002	134	134
RASGRP2	0.008	0.019	-10000	0	-0.14	2	2
RASGRP1	-0.023	0.15	0.22	11	-0.31	83	94
HLA-A	0.038	0.015	-10000	0	-0.002	67	67
RASSF5	0.039	0.01	-10000	0	0	33	33
RAP1A/GTP/RAPL	0.045	0.035	-10000	0	-0.11	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.06	0.15	16	-0.11	36	52
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.02	0.064	-10000	0	-0.16	73	73
PRKCA	-0.01	0.082	0.17	15	-0.19	55	70
GRAP2	0.038	0.013	-10000	0	0	55	55
mol:IP3	-0.016	0.11	-10000	0	-0.27	67	67
EntrezGene:6957	0.001	0.004	-10000	0	-0.022	2	2
TCR/CD3/MHC I/CD8	-0.01	0.12	-10000	0	-0.37	42	42
ORAI1	-0.076	0.28	-10000	0	-1.1	40	40
CSK	-0.014	0.16	0.23	11	-0.39	59	70
B7 family/CD28	0.027	0.16	0.27	6	-0.36	61	67
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	69	72
PTPN6	-0.011	0.16	0.2	31	-0.36	63	94
VAV1	-0.017	0.16	0.22	13	-0.4	62	75
Monovalent TCR/CD3	-0.004	0.082	-10000	0	-0.2	65	65
CBL	0.04	0.008	-10000	0	0	23	23
LCK	-0.018	0.17	0.23	16	-0.41	63	79
PAG1	-0.009	0.16	0.21	31	-0.4	57	88
RAP1A	0.039	0.01	-10000	0	0	35	35
TCR/CD3/MHC I/CD8/LCK	-0.022	0.16	0.2	4	-0.37	76	80
CD80	0.039	0.01	-10000	0	0	35	35
CD86	0.035	0.016	-10000	0	0	101	101
PDK1/CARD11/BCL10/MALT1	-0.007	0.084	-10000	0	-0.19	68	68
HRAS	0.04	0.009	-10000	0	0	29	29
GO:0035030	-0.013	0.13	0.19	16	-0.3	66	82
CD8A	0.042	0.01	-10000	0	-0.016	14	14
CD8B	0.001	0.004	-10000	0	-0.022	3	3
PTPRC	0.025	0.021	-10000	0	0	227	227
PDK1/PKC theta	-0.021	0.16	0.27	6	-0.37	67	73
CSK/PAG1	-0.008	0.16	0.24	20	-0.39	56	76
SOS1	0.038	0.013	-10000	0	0	57	57
peptide-MHC class I	0.037	0.07	-10000	0	-0.17	47	47
GRAP2/SLP76	-0.001	0.17	0.25	5	-0.38	68	73
STIM1	-0.021	0.074	1.1	1	-10000	0	1
RAS family/GTP	0.01	0.077	0.18	4	-0.16	49	53
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.017	0.15	0.17	3	-0.35	70	73
mol:DAG	-0.028	0.09	-10000	0	-0.24	69	69
RAP1A/GDP	0.01	0.033	0.081	11	-0.059	42	53
PLCG1	0.039	0.011	-10000	0	0	39	39
CD247	0.001	0.003	-10000	0	-0.023	2	2
cytotoxic T cell degranulation	-0.008	0.2	-10000	0	-0.74	27	27
RAP1A/GTP	0.003	0.011	-10000	0	-0.037	17	17
mol:PI-3-4-5-P3	-0.018	0.16	0.22	11	-0.36	72	83
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.01	0.14	0.22	1	-0.33	65	66
NRAS	0.039	0.01	-10000	0	0	31	31
ZAP70	0.041	0.006	-10000	0	0	11	11
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
LAT/GRAP2/SLP76/VAV1	-0.012	0.14	0.26	3	-0.34	63	66
MALT1	0.036	0.015	-10000	0	0	80	80
TRAF6	0.04	0.009	-10000	0	0	24	24
CD8 heterodimer	0.031	0.012	-10000	0	-0.041	4	4
CARD11	0.037	0.013	-10000	0	0	60	60
PRKCB	-0.028	0.061	-10000	0	-0.17	69	69
PRKCE	-0.007	0.083	0.18	16	-0.2	50	66
PRKCQ	-0.023	0.17	0.23	9	-0.4	70	79
LCP2	0.034	0.016	-10000	0	0	100	100
BCL10	0.041	0.006	-10000	0	0	12	12
regulation of survival gene product expression	-0.009	0.12	0.21	10	-0.27	72	82
IKK complex	0.003	0.049	0.14	16	-0.095	22	38
RAS family/GDP	-0.002	0.014	-10000	0	-0.035	40	40
MAP3K14	-0.002	0.093	0.17	12	-0.2	67	79
PDPK1	-0.015	0.13	0.22	12	-0.3	72	84
TCR/CD3/MHC I/CD8/Fyn	-0.038	0.2	-10000	0	-0.48	69	69

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.025	0.062	0.2	4	-0.21	38	42
RFC1	-0.023	0.061	0.17	3	-0.22	37	40
PRKDC	-0.019	0.071	0.21	15	-0.21	41	56
RIPK1	0.038	0.012	-10000	0	0	48	48
CASP7	0	0.12	-10000	0	-0.58	21	21
FASLG/FAS/FADD/FAF1	0.021	0.082	0.15	101	-0.17	38	139
MAP2K4	0.001	0.12	0.27	5	-0.33	36	41
mol:ceramide	0.017	0.095	-10000	0	-0.29	24	24
GSN	-0.025	0.062	0.2	3	-0.21	40	43
FASLG/FAS/FADD/FAF1/Caspase 8	0.026	0.091	0.21	13	-0.24	19	32
FAS	0.035	0.018	-10000	0	-0.002	104	104
BID	-0.034	0.024	0.23	2	-0.13	12	14
MAP3K1	-0.002	0.11	0.24	8	-0.36	31	39
MAP3K7	0.039	0.012	-10000	0	0	47	47
RB1	-0.026	0.062	0.18	2	-0.21	37	39
CFLAR	0.04	0.008	-10000	0	0	21	21
HGF/MET	-0.014	0.092	-10000	0	-0.14	165	165
ARHGDIB	-0.014	0.073	0.23	20	-0.22	27	47
FADD	0.041	0.012	-10000	0	-0.009	28	28
actin filament polymerization	0.025	0.061	0.21	40	-0.2	3	43
NFKB1	-0.053	0.24	-10000	0	-0.64	73	73
MAPK8	-0.002	0.12	0.3	3	-0.36	31	34
DFFA	-0.022	0.068	0.2	9	-0.21	44	53
DNA fragmentation during apoptosis	-0.023	0.062	0.19	5	-0.21	41	46
FAS/FADD/MET	0.017	0.089	-10000	0	-0.13	126	126
CFLAR/RIP1	0.052	0.032	-10000	0	-0.15	8	8
FAIM3	0.04	0.009	-10000	0	0	24	24
FAF1	0.041	0.014	-10000	0	-0.009	33	33
PARP1	-0.02	0.071	0.22	15	-0.21	39	54
DFFB	-0.023	0.062	0.19	5	-0.21	41	46
CHUK	-0.06	0.22	-10000	0	-0.61	72	72
FASLG	0.041	0.013	-10000	0	-0.044	8	8
FAS/FADD	0.037	0.061	-10000	0	-0.14	53	53
HGF	0.04	0.009	-10000	0	0	29	29
LMNA	-0.02	0.068	0.19	14	-0.22	31	45
CASP6	-0.018	0.061	0.14	2	-0.24	26	28
CASP10	0.037	0.017	-10000	0	-0.004	75	75
CASP3	-0.023	0.066	0.16	4	-0.23	44	48
PTPN13	0.021	0.021	-10000	0	0	276	276
CASP8	-0.031	0.02	0.26	2	-10000	0	2
IL6	-0.047	0.25	-10000	0	-0.71	42	42
MET	0.027	0.02	-10000	0	0	195	195
ICAD/CAD	-0.025	0.064	0.22	10	-0.2	43	53
FASLG/FAS/FADD/FAF1/Caspase 10	0.016	0.096	-10000	0	-0.29	24	24
activation of caspase activity by cytochrome c	-0.034	0.024	0.23	2	-0.13	12	14
PAK2	-0.025	0.061	0.14	2	-0.21	42	44
BCL2	0.036	0.014	-10000	0	0	76	76

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.035	0.048	-10000	0	-0.12	43	43
cell-cell adhesion	0.041	0.041	0.17	13	-10000	0	13
Ephrin B/EPHB2/RasGAP	0.052	0.097	-10000	0	-0.12	95	95
ITSN1	0.041	0.007	-10000	0	0	16	16
PIK3CA	0.03	0.019	-10000	0	0	150	150
SHC1	0.04	0.009	-10000	0	0	29	29
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	-0.017	0.11	-10000	0	-0.18	128	128
Ephrin B/EPHB1/GRB7	0.057	0.09	-10000	0	-0.12	82	82
Endophilin/SYNJ1	-0.025	0.06	0.19	12	-0.2	6	18
KRAS	0.034	0.016	-10000	0	0	103	103
Ephrin B/EPHB1/Src	0.062	0.088	-10000	0	-0.12	77	77
endothelial cell migration	0.021	0.076	-10000	0	-0.11	99	99
GRB2	0.041	0.007	-10000	0	0	14	14
GRB7	0.037	0.013	-10000	0	0	62	62
PAK1	-0.018	0.073	0.18	29	-0.2	11	40
HRAS	0.04	0.009	-10000	0	0	29	29
RRAS	-0.026	0.059	0.19	9	-0.2	12	21
DNM1	0.039	0.01	-10000	0	0	36	36
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.011	0.073	0.19	36	-0.18	5	41
lamellipodium assembly	-0.041	0.041	-10000	0	-0.17	13	13
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.072	-10000	0	-0.23	12	12
PIK3R1	0.034	0.016	-10000	0	0	106	106
EPHB2	0.039	0.011	-10000	0	0	38	38
EPHB3	0.032	0.018	-10000	0	0	133	133
EPHB1	0.038	0.013	-10000	0	0	57	57
EPHB4	0.04	0.009	-10000	0	0	27	27
mol:GDP	-0.042	0.097	0.19	13	-0.23	71	84
Ephrin B/EPHB2	0.048	0.081	-10000	0	-0.11	97	97
Ephrin B/EPHB3	0.035	0.077	-10000	0	-0.11	89	89
JNK cascade	-0.004	0.098	0.28	49	-0.18	3	52
Ephrin B/EPHB1	0.049	0.075	-10000	0	-0.11	82	82
RAP1/GDP	-0.025	0.12	0.31	4	-0.22	82	86
EFNB2	0.031	0.018	-10000	0	0	141	141
EFNB3	0.037	0.013	-10000	0	0	64	64
EFNB1	0.041	0.007	-10000	0	0	15	15
Ephrin B2/EPHB1-2	0.035	0.068	-10000	0	-0.11	77	77
RAP1B	0.038	0.013	-10000	0	0	57	57
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.029	0.099	-10000	0	-0.16	84	84
Rap1/GTP	-0.046	0.051	0.062	2	-0.19	17	19
axon guidance	0.034	0.048	-10000	0	-0.11	43	43
MAPK3	-0.003	0.069	0.2	7	-0.22	11	18
MAPK1	-0.002	0.068	0.19	7	-0.22	12	19
Rac1/GDP	-0.029	0.11	0.26	8	-0.21	76	84
actin cytoskeleton reorganization	-0.051	0.06	-10000	0	-0.16	72	72
CDC42/GDP	-0.029	0.11	0.27	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	0.079	-10000	0	-0.15	97	97
CDC42	0.04	0.008	-10000	0	0	22	22
RAS family/GTP	-0.041	0.049	-10000	0	-0.19	15	15
PTK2	0.16	0.26	0.56	166	-0.18	1	167
MAP4K4	-0.004	0.099	0.28	49	-0.19	3	52
SRC	0.039	0.01	-10000	0	0	31	31
KALRN	0.038	0.012	-10000	0	0	53	53
Intersectin/N-WASP	0.057	0.023	-10000	0	-0.14	5	5
neuron projection morphogenesis	-0.018	0.094	0.29	21	-0.22	12	33
MAP2K1	-0.001	0.066	0.21	2	-0.22	12	14
WASL	0.04	0.008	-10000	0	0	23	23
Ephrin B1/EPHB1-2/NCK1	0.076	0.065	-10000	0	-0.12	40	40
cell migration	-0.009	0.09	0.23	12	-0.25	17	29
NRAS	0.039	0.01	-10000	0	0	31	31
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	0.032	0.081	-10000	0	-0.12	87	87
Ephrin B1/EPHB1-2	0.062	0.043	-10000	0	-0.11	18	18
cell adhesion mediated by integrin	0.01	0.065	0.17	12	-0.22	15	27
RAC1	0.039	0.01	-10000	0	0	35	35
mol:GTP	0.036	0.083	-10000	0	-0.12	89	89
RAC1-CDC42/GTP	-0.041	0.046	-10000	0	-0.19	11	11
RASA1	0.036	0.014	-10000	0	0	73	73
RAC1-CDC42/GDP	-0.018	0.11	0.28	6	-0.21	74	80
ruffle organization	-0.021	0.082	0.22	17	-0.24	2	19
NCK1	0.036	0.014	-10000	0	0	77	77
receptor internalization	-0.03	0.055	0.17	11	-0.19	7	18
Ephrin B/EPHB2/KALRN	0.059	0.093	-10000	0	-0.12	86	86
ROCK1	0.02	0.088	0.19	107	-10000	0	107
RAS family/GDP	-0.056	0.063	-10000	0	-0.16	108	108
Rac1/GTP	-0.04	0.047	-10000	0	-0.18	13	13
Ephrin B/EPHB1/Src/Paxillin	0.004	0.073	-10000	0	-0.15	79	79

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.04	0.15	-10000	0	-0.34	97	97
KLHL20	-0.015	0.1	0.2	13	-0.22	57	70
CYFIP2	0.038	0.011	-10000	0	0	45	45
Rac1/GDP	-0.012	0.11	0.28	4	-0.25	50	54
ENAH	-0.038	0.14	-10000	0	-0.33	95	95
AP1M1	0.036	0.015	-10000	0	0	78	78
RAP1B	0.038	0.013	-10000	0	0	57	57
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.039	0.01	-10000	0	0	32	32
CDC42/GTP	0.002	0.08	0.16	4	-0.17	53	57
ABI1/Sra1/Nap1	-0.032	0.053	-10000	0	-0.16	60	60
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.068	0.068	-10000	0	-0.11	43	43
RAPGEF1	-0.037	0.13	0.28	3	-0.3	87	90
CTNND1	0.041	0.007	-10000	0	0	17	17
regulation of calcium-dependent cell-cell adhesion	-0.03	0.16	-10000	0	-0.34	101	101
CRK	-0.034	0.14	0.25	1	-0.32	86	87
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	-0.13	17	17
IQGAP1	0.037	0.014	-10000	0	0	67	67
NCKAP1	0.039	0.01	-10000	0	0	33	33
Rap1/GTP/I-afadin	0.042	0.065	-10000	0	-0.11	64	64
DLG1	-0.044	0.15	-10000	0	-0.34	102	102
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.034	0.048	-10000	0	-0.15	55	55
MLLT4	0.033	0.017	-10000	0	0	110	110
ARF6/GTP/NME1/Tiam1	0.046	0.062	-10000	0	-0.11	57	57
PI3K	-0.04	0.063	-10000	0	-0.19	53	53
ARF6	0.04	0.007	-10000	0	0	18	18
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	70	70
E-cadherin(dimer)/Ca2+	0.063	0.072	-10000	0	-0.13	51	51
AKT1	-0.008	0.062	0.16	14	-0.16	18	32
PIK3R1	0.034	0.016	-10000	0	0	106	106
CDH1	0.035	0.016	-10000	0	0	96	96
RhoA/GDP	-0.013	0.11	0.22	5	-0.25	53	58
actin cytoskeleton organization	-0.009	0.076	0.16	14	-0.16	55	69
CDC42/GDP	-0.012	0.11	0.28	4	-0.25	48	52
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.002	0.073	-10000	0	-0.19	55	55
ITGB7	0.039	0.011	-10000	0	0	39	39
RAC1	0.039	0.01	-10000	0	0	35	35
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.068	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	-0.28	50	54
CDC42/GTP/IQGAP1	0.04	0.046	-10000	0	-0.11	40	40
JUP	0.037	0.014	-10000	0	0	67	67
p120 catenin/RhoA/GDP	-0.001	0.12	0.23	4	-0.25	54	58
RAC1/GTP/IQGAP1	0.038	0.046	-10000	0	-0.11	40	40
PIP5K1C/AP1M1	0.048	0.027	-10000	0	-0.14	1	1
RHOA	0.041	0.007	-10000	0	0	14	14
CDC42	0.04	0.008	-10000	0	0	22	22
CTNNA1	0.039	0.01	-10000	0	0	36	36
positive regulation of S phase of mitotic cell cycle	-0.015	0.059	0.12	4	-0.12	97	101
NME1	0.035	0.015	-10000	0	0	87	87
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.039	0.15	-10000	0	-0.34	93	93
regulation of cell-cell adhesion	-0.009	0.065	-10000	0	-0.15	56	56
WASF2	-0.006	0.042	0.098	12	-0.091	49	61
Rap1/GTP	0.001	0.087	0.21	7	-0.22	34	41
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.072	0.082	-10000	0	-0.12	45	45
CCND1	-0.019	0.071	0.14	4	-0.15	97	101
VAV2	-0.047	0.21	-10000	0	-0.6	48	48
RAP1/GDP	0	0.098	0.25	5	-0.26	30	35
adherens junction assembly	-0.039	0.14	-10000	0	-0.33	94	94
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.04	0.009	-10000	0	0	28	28
PIP5K1C	0.037	0.013	-10000	0	0	63	63
regulation of heterotypic cell-cell adhesion	0.046	0.076	0.22	6	-0.13	58	64
E-cadherin/beta catenin	0.007	0.04	0.15	1	-0.23	12	13
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.038	0.14	-10000	0	-0.33	94	94
PIK3CA	0.03	0.019	-10000	0	0	150	150
Rac1/GTP	-0.054	0.13	-10000	0	-0.35	63	63
E-cadherin/beta catenin/alpha catenin	0.052	0.065	-10000	0	-0.13	48	48
ITGAE	0.039	0.01	-10000	0	0	34	34
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.031	0.16	-10000	0	-0.34	101	101

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.048	0.065	-9999	-0.12	49	49
E-cadherin/beta catenin	0.04	0.051	-9999	-0.14	35	35
CTNNB1	0.039	0.01	-9999	0	32	32
JUP	0.037	0.014	-9999	0	67	67
CDH1	0.035	0.016	-9999	0	96	96

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.032	0.1	0.21	19	-0.25	25	44
TBX21	-0.026	0.28	-10000	0	-0.75	43	43
B2M	0.038	0.014	-10000	0	-10000	0	0
TYK2	0.025	0.044	-10000	0	-0.058	39	39
IL12RB1	0.025	0.045	-10000	0	-0.057	46	46
GADD45B	-0.057	0.35	-10000	0	-0.93	56	56
IL12RB2	0.028	0.045	-10000	0	-0.056	48	48
GADD45G	-0.029	0.3	-10000	0	-0.83	42	42
natural killer cell activation	0.002	0.021	0.048	10	-0.038	50	60
RELB	0.04	0.009	-10000	0	0	25	25
RELA	0.041	0.006	-10000	0	0	10	10
IL18	0.03	0.025	-10000	0	-0.042	20	20
IL2RA	0.038	0.012	-10000	0	0	49	49
IFNG	0.037	0.013	-10000	0	0	59	59
STAT3 (dimer)	-0.022	0.28	0.41	1	-0.66	59	60
HLA-DRB5	0.019	0.028	-10000	0	-0.008	262	262
FASLG	-0.023	0.28	0.53	1	-0.75	44	45
NF kappa B2 p52/RelB	-0.011	0.29	0.42	1	-0.66	60	61
CD4	0.025	0.028	-10000	0	-0.012	186	186
SOCS1	0.038	0.012	-10000	0	0	52	52
EntrezGene:6955	-0.001	0.01	-10000	0	-0.026	55	55
CD3D	0.027	0.03	-10000	0	-0.04	66	66
CD3E	0.028	0.029	-10000	0	-0.037	68	68
CD3G	0.026	0.029	-10000	0	-0.041	56	56
IL12Rbeta2/JAK2	0.031	0.073	-10000	0	-0.15	29	29
CCL3	-0.042	0.32	-10000	0	-0.88	50	50
CCL4	-0.026	0.28	-10000	0	-0.66	59	59
HLA-A	0.038	0.014	-10000	0	-10000	0	0
IL18/IL18R	0.061	0.081	0.2	1	-0.11	80	81
NOS2	-0.023	0.27	0.41	2	-0.6	67	69
IL12/IL12R/TYK2/JAK2/SPHK2	0.031	0.1	0.21	20	-0.24	27	47
IL1R1	-0.1	0.43	-10000	0	-0.99	91	91
IL4	0.019	0.044	0.099	1	-0.062	17	18
JAK2	0.023	0.042	-10000	0	-0.056	48	48
EntrezGene:6957	-0.001	0.009	-10000	0	-0.025	18	18
TCR/CD3/MHC I/CD8	-0.012	0.11	-10000	0	-0.45	23	23
RAB7A	-0.029	0.27	-10000	0	-0.61	70	70
lysosomal transport	-0.025	0.26	-10000	0	-0.58	71	71
FOS	-0.18	0.51	-10000	0	-1.1	126	126
STAT4 (dimer)	-0.017	0.29	0.42	2	-0.66	63	65
STAT5A (dimer)	-0.019	0.28	0.42	1	-0.66	57	58
GZMA	-0.05	0.34	-10000	0	-0.95	51	51
GZMB	-0.033	0.31	0.56	1	-0.86	47	48
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.032	0.29	0.42	3	-0.71	56	59
TCR/CD3/MHC II/CD4	-0.07	0.2	-10000	0	-0.37	134	134
IL2/IL2R	0.046	0.082	-10000	0	-0.11	92	92
MAPK14	-0.045	0.32	-10000	0	-0.76	67	67
CCR5	-0.017	0.25	0.42	1	-0.55	67	68
IL1B	0.023	0.042	-10000	0	-0.057	35	35
STAT6	0.011	0.14	-10000	0	-0.61	13	13
STAT4	0.04	0.009	-10000	0	0	28	28
STAT3	0.038	0.012	-10000	0	0	52	52
STAT1	0.034	0.017	-10000	0	0	108	108
NFKB1	0.035	0.015	-10000	0	0	85	85
NFKB2	0.04	0.008	-10000	0	0	23	23
IL12B	0.028	0.045	-10000	0	-0.057	46	46
CD8A	0.042	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	-0.032	0.1	0.25	24	-0.21	19	43
IL2RB	0.037	0.014	-10000	0	0	70	70
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.27	0.42	2	-0.61	63	65
IL2RG	0.028	0.02	-10000	0	0	181	181
IL12	0.024	0.071	-10000	0	-0.15	31	31
STAT5A	0.038	0.012	-10000	0	0	50	50
CD247	-0.001	0.009	-10000	0	-0.025	18	18
IL2	0.038	0.012	-10000	0	0	47	47
SPHK2	0.04	0.008	-10000	0	0	23	23
FRAP1	0.04	0.009	-10000	0	0	24	24
IL12A	0.02	0.04	-10000	0	-0.056	40	40
IL12/IL12R/TYK2/JAK2	-0.043	0.29	-10000	0	-0.75	57	57
MAP2K3	-0.048	0.34	-10000	0	-0.78	67	67
RIPK2	0.032	0.018	-10000	0	0	125	125
MAP2K6	-0.052	0.32	-10000	0	-0.72	72	72
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.023	0.029	-10000	0	-0.011	205	205
IL18RAP	0.04	0.019	-10000	0	-0.042	24	24
IL12Rbeta1/TYK2	0.039	0.057	-10000	0	-0.091	2	2
EOMES	0.003	0.079	-10000	0	-0.53	8	8
STAT1 (dimer)	-0.039	0.29	0.42	1	-0.66	66	67
T cell proliferation	-0.016	0.24	0.37	2	-0.51	66	68
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	-0.029	0.25	-10000	0	-0.56	66	66
ATF2	-0.042	0.3	0.58	1	-0.7	69	70

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.068	0.14	13	-0.19	54	67
CRKL	0.039	0.01	-10000	0	0	35	35
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
DOCK1	0.037	0.013	-10000	0	0	63	63
ITGA4	0.035	0.015	-10000	0	0	90	90
alpha4/beta7 Integrin/MAdCAM1	0.065	0.074	-10000	0	-0.11	67	67
EPO	0.04	0.007	-10000	0	0	18	18
alpha4/beta7 Integrin	0.032	0.066	-10000	0	-0.14	65	65
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.011	-10000	0	0	45	45
alpha4/beta1 Integrin	0.032	0.065	-10000	0	-0.14	64	64
EPO/EPOR (dimer)	0.052	0.025	-10000	0	-0.14	2	2
lamellipodium assembly	0.016	0.11	0.21	1	-0.34	20	21
PIK3CA	0.03	0.019	-10000	0	0	150	150
PI3K	0.024	0.062	-10000	0	-0.15	47	47
ARF6	0.04	0.007	-10000	0	0	18	18
JAK2	0.006	0.066	-10000	0	-0.18	51	51
PXN	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.016	-10000	0	0	106	106
MADCAM1	0.037	0.014	-10000	0	0	69	69
cell adhesion	0.063	0.073	-10000	0	-0.11	67	67
CRKL/CBL	0.055	0.02	-10000	0	-0.14	1	1
ITGB1	0.039	0.011	-10000	0	0	39	39
SRC	-0.018	0.091	0.18	38	-0.19	39	77
ITGB7	0.039	0.011	-10000	0	0	39	39
RAC1	0.039	0.01	-10000	0	0	35	35
alpha4/beta1 Integrin/VCAM1	-0.006	0.095	-10000	0	-0.14	152	152
p130Cas/Crk/Dock1	0.012	0.1	0.22	21	-0.19	42	63
VCAM1	0.02	0.021	-10000	0	0	287	287
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	-0.019	0.082	0.2	23	-0.18	39	62
EPOR	0.036	0.014	-10000	0	0	75	75
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.04	0.008	-10000	0	0	23	23
GIT1	0.04	0.008	-10000	0	0	23	23
Rac1/GTP	0.016	0.11	0.21	1	-0.36	20	21

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.038	0.012	-10000	0	0	54	54
HDAC3	0.041	0.006	-10000	0	0	12	12
VDR	0.037	0.013	-10000	0	0	58	58
Cbp/p300/PCAF	0.04	0.043	-10000	0	-0.14	24	24
EP300	0.036	0.014	-10000	0	0	72	72
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.012	0.096	0.18	1	-0.26	48	49
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.04	0.009	-10000	0	0	28	28
AKT1	0.011	0.092	0.17	72	-0.2	28	100
RAR alpha/9cRA/Cyclin H	-0.003	0.12	-10000	0	-0.24	73	73
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.002	0.078	-10000	0	-0.21	51	51
CDC2	0.026	0.024	-10000	0	-0.005	192	192
response to UV	-0.001	0.008	-10000	0	-0.026	42	42
RAR alpha/Jnk1	0.017	0.069	-10000	0	-0.16	42	42
NCOR2	0.04	0.009	-10000	0	0	26	26
VDR/VDR/Vit D3	0.022	0.032	-10000	0	-0.13	23	23
RXRs/RARs/NRIP1/9cRA	-0.039	0.19	-10000	0	-0.5	62	62
NCOA2	0.037	0.014	-10000	0	0	69	69
NCOA3	0.036	0.014	-10000	0	0	77	77
NCOA1	0.04	0.009	-10000	0	0	28	28
VDR/VDR/DNA	0.037	0.013	-10000	0	0	58	58
RARG	0.035	0.021	-10000	0	-0.018	69	69
RAR gamma1/9cRA	0.042	0.033	-10000	0	-0.11	15	15
MAPK3	0.035	0.022	-10000	0	-0.026	60	60
MAPK1	0.039	0.011	-10000	0	0	43	43
MAPK8	0.034	0.024	-10000	0	-0.026	70	70
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.014	0.14	-10000	0	-0.32	77	77
RARA	0.006	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	-0.004	0.081	-10000	0	-0.22	50	50
PRKCA	0.03	0.032	-10000	0	-0.072	36	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.046	0.2	-10000	0	-0.55	61	61
RXRG	0.014	0.059	-10000	0	-0.19	31	31
RXRA	-0.027	0.096	-10000	0	-0.24	52	52
RXRB	0.011	0.061	-10000	0	-0.2	35	35
VDR/Vit D3/DNA	0.022	0.032	-10000	0	-0.13	23	23
RBP1	0.03	0.019	-10000	0	0	159	159
CRBP1/9-cic-RA	0.002	0.057	-10000	0	-0.13	89	89
RARB	0.032	0.026	-10000	0	-0.015	117	117
PRKCG	0.035	0.032	-10000	0	-0.071	45	45
MNAT1	0.04	0.008	-10000	0	0	22	22
RAR alpha/RXRs	-0.016	0.16	0.28	3	-0.36	73	76
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.01	0.13	-10000	0	-0.3	61	61
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.1	0.18	1	-0.27	47	48
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.046	0.2	-10000	0	-0.55	61	61
positive regulation of DNA binding	-0.01	0.11	-10000	0	-0.23	74	74
NRIP1	-0.083	0.32	-10000	0	-0.97	56	56
RXRs/RARs	-0.028	0.17	-10000	0	-0.4	76	76
RXRs/RXRs/DNA/9cRA	-0.032	0.14	-10000	0	-0.32	82	82
PRKACA	0.035	0.015	-10000	0	0	87	87
CDK7	0.035	0.016	-10000	0	0	94	94
TFIIH	0.059	0.055	-10000	0	-0.14	25	25
RAR alpha/9cRA	0.035	0.087	-10000	0	-0.22	20	20
CCNH	0.037	0.014	-10000	0	0	69	69
CREBBP	0.038	0.012	-10000	0	0	49	49
RAR gamma2/9cRA	0.043	0.062	-10000	0	-0.13	36	36

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.007	0.051	-10000	0	-0.15	39	39
EPHB2	0.039	0.011	-10000	0	0	38	38
Syndecan-2/TACI	0.025	0.041	-10000	0	-0.11	38	38
LAMA1	0.034	0.017	-10000	0	0	108	108
Syndecan-2/alpha2 ITGB1	0.039	0.086	-10000	0	-0.12	81	81
HRAS	0.04	0.009	-10000	0	0	29	29
Syndecan-2/CASK	0.001	0.028	-10000	0	-0.098	39	39
ITGA5	0.037	0.013	-10000	0	0	58	58
BAX	0.021	0.067	-10000	0	-10000	0	0
EPB41	0.039	0.01	-10000	0	0	33	33
positive regulation of cell-cell adhesion	0.016	0.046	-10000	0	-0.098	66	66
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	111	111
Syndecan-2/MMP2	0.007	0.052	-10000	0	-0.16	39	39
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.034	0.057	-10000	0	-0.14	44	44
dendrite morphogenesis	0.025	0.043	-10000	0	-0.12	37	37
Syndecan-2/GM-CSF	0.026	0.041	-10000	0	-0.11	38	38
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	37	37
GNB2L1	0.041	0.005	-10000	0	0	7	7
MAPK3	0.01	0.075	0.2	64	-10000	0	64
MAPK1	0.011	0.075	0.2	64	-10000	0	64
Syndecan-2/RACK1	0.041	0.047	-10000	0	-0.094	42	42
NF1	0.034	0.016	-10000	0	0	98	98
FGFR/FGF/Syndecan-2	0.01	0.007	-10000	0	-10000	0	0
ITGA2	0.033	0.017	-10000	0	0	122	122
MAPK8	0	0.02	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.052	0.077	0.19	42	-0.11	53	95
Syndecan-2/Kininogen	0.022	0.039	-10000	0	-0.11	34	34
ITGB1	0.039	0.011	-10000	0	0	39	39
SRC	0.007	0.074	0.19	68	-10000	0	68
Syndecan-2/CASK/Protein 4.1	0.023	0.037	-10000	0	-0.094	41	41
extracellular matrix organization	0.024	0.041	-10000	0	-0.11	35	35
actin cytoskeleton reorganization	0.007	0.051	-10000	0	-0.15	39	39
Syndecan-2/Caveolin-2/Ras	0.03	0.059	-10000	0	-0.11	60	60
Syndecan-2/Laminin alpha3	0.019	0.044	-10000	0	-0.13	32	32
Syndecan-2/RasGAP	0.063	0.069	0.18	2	-0.096	55	57
alpha5/beta1 Integrin	0.045	0.046	-10000	0	-0.14	28	28
PRKCD	0.038	0.013	-10000	0	0	55	55
Syndecan-2 dimer	0.025	0.043	-10000	0	-0.12	37	37
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	0.058	0.2	1	-0.099	49	50
RHOA	0.041	0.007	-10000	0	0	14	14
SDCBP	0.036	0.014	-10000	0	0	77	77
TNFRSF13B	0.039	0.011	-10000	0	0	38	38
RASA1	0.036	0.014	-10000	0	0	73	73
alpha2/beta1 Integrin	0.034	0.057	-10000	0	-0.14	44	44
Syndecan-2/Synbindin	0.021	0.042	-10000	0	-0.11	37	37
TGFB1	0.037	0.013	-10000	0	0	61	61
CASP3	0.004	0.07	0.2	50	-0.18	1	51
FN1	0.021	0.021	-10000	0	0	273	273
Syndecan-2/IL8	0.018	0.043	-10000	0	-0.12	35	35
SDC2	0.01	0.007	-10000	0	-10000	0	0
KNG1	0.034	0.017	-10000	0	0	108	108
Syndecan-2/Neurofibromin	0.022	0.042	-10000	0	-0.12	34	34
TRAPPC4	0.034	0.016	-10000	0	0	98	98
CSF2	0.04	0.009	-10000	0	0	24	24
Syndecan-2/TGFB1	0.024	0.042	-10000	0	-0.11	35	35
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.046	-10000	0	-0.098	66	66
Syndecan-2/Ezrin	0.024	0.038	-10000	0	-0.094	42	42
PRKACA	0.001	0.071	0.2	46	-0.16	4	50
angiogenesis	0.018	0.043	-10000	0	-0.12	35	35
MMP2	0.021	0.021	-10000	0	0	269	269
IL8	0.031	0.018	-10000	0	0	137	137
calcineurin-NFAT signaling pathway	0.025	0.041	-10000	0	-0.11	38	38

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	0.067	0.065	-10000	0	-0.1	53	53
ER alpha/Gai/GDP/Gbeta gamma	-0.022	0.13	-10000	0	-0.34	45	45
AKT1	-0.089	0.27	-10000	0	-0.65	95	95
PIK3CA	0.03	0.019	-10000	0	0	150	150
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.089	0.28	-10000	0	-0.66	96	96
mol:Ca2+	-0.007	0.071	0.18	9	-0.28	24	33
IGF1R	0.033	0.017	-10000	0	0	116	116
E2/ER alpha (dimer)/Striatin	0.035	0.05	-10000	0	-0.11	49	49
SHC1	0.04	0.009	-10000	0	0	29	29
apoptosis	0.085	0.26	0.62	95	-10000	0	95
RhoA/GTP	0.014	0.048	-10000	0	-0.11	59	59
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.006	0.14	-10000	0	-0.29	64	64
regulation of stress fiber formation	0.015	0.07	0.16	15	-0.16	41	56
E2/ERA-ERB (dimer)	0.037	0.046	-10000	0	-0.11	42	42
KRAS	0.034	0.016	-10000	0	0	103	103
G13/GTP	0.033	0.046	-10000	0	-0.1	51	51
pseudopodium formation	-0.015	0.07	0.16	41	-0.16	15	56
E2/ER alpha (dimer)/PELP1	0.036	0.046	-10000	0	-0.11	42	42
GRB2	0.041	0.007	-10000	0	0	14	14
GNG2	0.039	0.01	-10000	0	0	34	34
GNAO1	0.034	0.016	-10000	0	0	101	101
HRAS	0.04	0.009	-10000	0	0	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.037	0.16	-10000	0	-0.38	79	79
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	-0.037	0.16	-10000	0	-0.38	79	79
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	-0.005	0.07	0.18	6	-0.29	24	30
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	116	116
PLCB1	0.003	0.069	-10000	0	-0.3	23	23
PLCB2	0.004	0.067	-10000	0	-0.28	26	26
IGF1	0.036	0.015	-10000	0	0	82	82
mol:L-citrulline	-0.037	0.16	-10000	0	-0.38	79	79
RHOA	0.041	0.007	-10000	0	0	14	14
Gai/GDP	-0.017	0.19	-10000	0	-0.57	56	56
JNK cascade	0.03	0.005	-10000	0	-10000	0	0
BCAR1	0.036	0.014	-10000	0	0	74	74
ESR2	0.041	0.007	-10000	0	0	17	17
GNAQ	0.038	0.012	-10000	0	0	50	50
ESR1	0.035	0.016	-10000	0	0	92	92
Gq family/GDP/Gbeta gamma	-0.04	0.23	-10000	0	-0.63	67	67
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.024	0.1	-10000	0	-0.65	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.007	0.14	-10000	0	-0.29	65	65
GNAZ	0.039	0.011	-10000	0	0	38	38
E2/ER alpha (dimer)	0.016	0.042	-10000	0	-0.13	42	42
STRN	0.039	0.01	-10000	0	0	31	31
GNAL	0.04	0.009	-10000	0	0	27	27
PELP1	0.04	0.009	-10000	0	0	29	29
MAPK11	0.014	0.008	0.069	1	-10000	0	1
GNAI2	0.041	0.006	-10000	0	0	13	13
GNAI3	0.038	0.012	-10000	0	0	46	46
GNAI1	0.035	0.016	-10000	0	0	94	94
HBEGF	-0.017	0.14	0.31	15	-0.34	45	60
cAMP biosynthetic process	0.032	0.038	-10000	0	-0.092	39	39
SRC	-0.022	0.13	0.24	2	-0.34	43	45
PI3K	0.024	0.062	-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	57	57
IGF-1R heterotetramer/IGF1	-0.038	0.1	-10000	0	-0.26	61	61
Gs family/GTP	0.041	0.043	-10000	0	-0.093	39	39
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.054	0.05	-10000	0	-0.11	28	28
vasodilation	-0.035	0.15	-10000	0	-0.36	79	79
mol:DAG	-0.005	0.07	0.18	6	-0.29	24	30
Gs family/GDP/Gbeta gamma	0.003	0.081	-10000	0	-0.21	50	50
MSN	-0.017	0.072	0.15	60	-0.17	16	76
Gq family/GTP	0.017	0.073	-10000	0	-0.29	25	25
mol:PI-3-4-5-P3	-0.085	0.27	-10000	0	-0.62	102	102
NRAS	0.039	0.01	-10000	0	0	31	31
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.035	0.15	0.36	79	-10000	0	79
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
RhoA/GDP	0.013	0.09	-10000	0	-0.21	57	57
NOS3	-0.039	0.17	-10000	0	-0.39	79	79
GNA11	0.037	0.013	-10000	0	0	63	63
MAPKKK cascade	-0.027	0.18	-10000	0	-0.46	74	74
E2/ER alpha (dimer)/PELP1/Src	-0.012	0.14	0.25	1	-0.3	69	70
ruffle organization	-0.015	0.07	0.16	41	-0.16	15	56
ROCK2	-0.008	0.082	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	-0.018	0.14	0.37	15	-0.33	45	60
MMP2	-0.019	0.13	0.26	3	-0.35	37	40

×

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	80	-0.18	5	85
DAPP1	-0.006	0.1	0.22	6	-0.26	38	44
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.011	0.14	-10000	0	-0.35	51	51
mol:DAG	0.005	0.075	0.18	23	-0.16	29	52
HRAS	0.041	0.013	0.079	3	-0.004	33	36
RAP1A	0.041	0.012	0.069	4	-0.001	36	40
ARF5/GDP	0.016	0.097	0.2	1	-0.24	40	41
PLCG2	0.036	0.015	-10000	0	0	83	83
PLCG1	0.039	0.011	-10000	0	0	39	39
ARF5	0.038	0.011	-10000	0	0	44	44
mol:GTP	-0.012	0.067	0.14	79	-0.18	4	83
ARF1/GTP	0.002	0.064	0.14	84	-0.17	4	88
RHOA	0.041	0.007	-10000	0	0	14	14
YES1	0.037	0.013	-10000	0	0	59	59
RAP1A/GTP	-0.006	0.078	0.16	83	-0.18	4	87
ADAP1	-0.014	0.061	0.13	72	-0.18	4	76
ARAP3	-0.012	0.066	0.14	79	-0.18	4	83
INPPL1	0.04	0.009	-10000	0	0	29	29
PREX1	0.037	0.013	-10000	0	0	58	58
ARHGEF6	0.037	0.013	-10000	0	0	64	64
ARHGEF7	0.04	0.009	-10000	0	0	30	30
ARF1	0.038	0.012	-10000	0	0	51	51
NRAS	0.042	0.011	0.068	3	0	31	34
FYN	0.034	0.016	-10000	0	0	102	102
ARF6	0.04	0.007	-10000	0	0	18	18
FGR	0.041	0.007	-10000	0	0	16	16
mol:Ca2+	0.001	0.047	0.15	16	-0.11	10	26
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.037	0.014	-10000	0	0	70	70
ZAP70	0.041	0.006	-10000	0	0	11	11
mol:IP3	-0.003	0.058	0.18	13	-0.14	16	29
LYN	0.036	0.015	-10000	0	0	83	83
ARF1/GDP	0.017	0.097	0.2	1	-0.25	37	38
RhoA/GDP	0.036	0.085	0.19	47	-0.17	24	71
PDK1/Src/Hsp90	0.05	0.022	-10000	0	-0.11	5	5
BLNK	0.037	0.014	-10000	0	0	67	67
actin cytoskeleton reorganization	0.009	0.094	0.23	17	-0.25	24	41
SRC	0.039	0.01	-10000	0	0	31	31
PLEKHA2	-0.014	0.006	-10000	0	-10000	0	0
RAC1	0.039	0.01	-10000	0	0	35	35
PTEN	0.031	0.028	-10000	0	-0.03	79	79
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.075	0.15	85	-0.18	4	89
RhoA/GTP	-0.009	0.08	0.16	87	-0.18	5	92
Src family/SYK family/BLNK-LAT	0.001	0.098	-10000	0	-0.28	30	30
BLK	0.033	0.017	-10000	0	0	115	115
PDPK1	0.04	0.009	-10000	0	0	27	27
CYTH1	-0.014	0.061	0.13	72	-0.18	4	76
HCK	0.036	0.015	-10000	0	0	79	79
CYTH3	-0.014	0.061	0.13	72	-0.18	4	76
CYTH2	-0.014	0.061	0.13	72	-0.18	4	76
KRAS	0.034	0.018	0.091	1	-0.001	106	107
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.011	0.044	0.16	2	-0.16	9	11
SGK1	0.011	0.043	-10000	0	-0.17	9	9
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.094	0.2	2	-0.25	40	42
SOS1	0.038	0.013	-10000	0	0	57	57
SYK	0.037	0.014	-10000	0	0	67	67
ARF6/GDP	0.003	0.08	0.17	60	-0.17	16	76
mol:PI-3-4-5-P3	-0.014	0.064	0.14	72	-0.18	4	76
ARAP3/RAP1A/GTP	-0.006	0.078	0.17	83	-0.18	4	87
VAV1	0.037	0.014	-10000	0	0	67	67
mol:PI-3-4-P2	-0.01	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.044	0.065	0.22	28	-0.12	38	66
PLEKHA1	-0.015	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.1	0.22	1	-0.24	40	41
LAT	0.041	0.006	-10000	0	0	13	13
Rac1/GTP	-0.005	0.1	-10000	0	-0.27	48	48
ITK	-0.013	0.066	0.13	79	-0.18	5	84
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.001	0.092	0.2	18	-0.22	32	50
LCK	0.04	0.009	-10000	0	0	28	28
BTK	-0.013	0.069	0.13	80	-0.19	8	88

×

BCR signaling pathway

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
JUN	-0.047	0.14	-10000	0	-0.34	61	61
IKBKB	0.018	0.097	0.27	7	-0.29	14	21
AKT1	0.024	0.093	0.22	47	-0.18	9	56
IKBKG	0.02	0.078	0.23	1	-0.27	9	10
CALM1	-0.011	0.12	0.21	6	-0.36	35	41
PIK3CA	0.03	0.019	-10000	0	0	150	150
MAP3K1	-0.046	0.16	-10000	0	-0.47	42	42
MAP3K7	0.038	0.012	-10000	0	0	47	47
mol:Ca2+	-0.01	0.12	0.21	4	-0.37	40	44
DOK1	0.04	0.009	-10000	0	0	24	24
AP-1	-0.023	0.093	-10000	0	-0.22	55	55
LYN	0.035	0.015	-10000	0	0	83	83
BLNK	0.037	0.014	-10000	0	0	67	67
SHC1	0.04	0.009	-10000	0	0	29	29
BCR complex	0.053	0.024	-10000	0	-0.13	3	3
CD22	-0.011	0.087	-10000	0	-0.27	35	35
CAMK2G	-0.014	0.11	0.22	5	-0.34	37	42
CSNK2A1	0.039	0.011	-10000	0	0	40	40
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.021	0.063	-10000	0	-0.13	58	58
GO:0007205	-0.011	0.13	0.21	4	-0.37	41	45
SYK	0.037	0.014	-10000	0	0	67	67
ELK1	-0.015	0.12	0.22	3	-0.36	41	44
NFATC1	-0.025	0.11	0.22	3	-0.28	47	50
B-cell antigen/BCR complex	0.053	0.024	-10000	0	-0.13	3	3
PAG1/CSK	0.052	0.027	-10000	0	-0.14	5	5
NFKBIB	0.011	0.067	0.13	1	-0.13	82	83
HRAS	-0.009	0.098	0.25	3	-0.28	38	41
NFKBIA	0.014	0.062	0.13	1	-0.12	71	72
NF-kappa-B/RelA/I kappa B beta	0.02	0.059	0.13	2	-0.11	65	67
RasGAP/Csk	0.056	0.088	-10000	0	-0.11	80	80
mol:GDP	-0.01	0.12	0.21	4	-0.36	41	45
PTEN	0.039	0.011	-10000	0	0	39	39
CD79B	0.04	0.008	-10000	0	0	19	19
NF-kappa-B/RelA/I kappa B alpha	0.022	0.056	0.13	2	-0.11	43	45
GRB2	0.041	0.007	-10000	0	0	14	14
PI3K/BCAP/CD19	-0.026	0.15	-10000	0	-0.42	39	39
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	-0.007	0.12	0.21	4	-0.38	39	43
CSK	0.04	0.008	-10000	0	0	22	22
FOS	-0.016	0.12	0.23	4	-0.33	45	49
CHUK	-0.003	0.12	0.23	1	-0.29	49	50
IBTK	0.037	0.014	-10000	0	0	66	66
CARD11/BCL10/MALT1/TAK1	0.014	0.12	-10000	0	-0.3	43	43
PTPN6	-0.003	0.089	0.2	5	-0.27	25	30
RELA	0.041	0.006	-10000	0	0	10	10
BCL2A1	0.014	0.044	0.11	3	-0.086	45	48
VAV2	-0.021	0.11	-10000	0	-0.32	50	50
ubiquitin-dependent protein catabolic process	0.015	0.065	0.13	1	-0.12	82	83
BTK	-0.036	0.25	-10000	0	-1.1	31	31
CD19	-0.019	0.095	-10000	0	-0.29	37	37
MAP4K1	0.039	0.011	-10000	0	0	43	43
CD72	0.04	0.008	-10000	0	0	20	20
PAG1	0.038	0.013	-10000	0	0	55	55
MAPK14	-0.038	0.15	0.31	1	-0.4	43	44
SH3BP5	0.04	0.008	-10000	0	0	23	23
PIK3AP1	-0.009	0.12	0.24	4	-0.4	35	39
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.018	0.17	-10000	0	-0.51	42	42
RAF1	-0.013	0.093	0.24	5	-0.27	37	42
RasGAP/p62DOK/SHIP	0.044	0.078	-10000	0	-0.11	82	82
CD79A	0.037	0.013	-10000	0	0	57	57
re-entry into mitotic cell cycle	-0.023	0.092	-10000	0	-0.21	56	56
RASA1	0.036	0.014	-10000	0	0	73	73
MAPK3	-0.019	0.083	0.23	6	-0.26	32	38
MAPK1	-0.017	0.082	0.22	8	-0.25	31	39
CD72/SHP1	0.025	0.12	0.29	22	-0.26	26	48
NFKB1	0.035	0.015	-10000	0	0	85	85
MAPK8	-0.043	0.14	-10000	0	-0.41	42	42
actin cytoskeleton organization	-0.023	0.11	0.24	3	-0.29	46	49
NF-kappa-B/RelA	0.032	0.12	-10000	0	-0.25	49	49
Calcineurin	0.013	0.12	0.28	1	-0.31	39	40
PI3K	-0.01	0.075	-10000	0	-0.26	18	18
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.001	0.12	0.22	4	-0.38	36	40
SOS1	0.038	0.013	-10000	0	0	57	57
Bam32/HPK1	-0.054	0.25	-10000	0	-0.68	64	64
DAPP1	-0.077	0.27	-10000	0	-0.76	63	63
cytokine secretion	-0.023	0.1	0.21	3	-0.27	47	50
mol:DAG	-0.007	0.12	0.21	4	-0.38	39	43
PLCG2	0.036	0.015	-10000	0	0	83	83
MAP2K1	-0.016	0.089	0.23	7	-0.27	34	41
B-cell antigen/BCR complex/FcgammaRIIB	0.038	0.071	-10000	0	-0.12	73	73
mol:PI-3-4-5-P3	0.01	0.093	0.22	34	-0.23	10	44
ETS1	-0.012	0.11	0.25	8	-0.32	38	46
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.07	0.083	-10000	0	-0.12	50	50
B-cell antigen/BCR complex/LYN	-0.012	0.1	-10000	0	-0.3	38	38
MALT1	0.036	0.015	-10000	0	0	80	80
TRAF6	0.04	0.009	-10000	0	0	24	24
RAC1	-0.023	0.11	0.25	3	-0.31	45	48
B-cell antigen/BCR complex/LYN/SYK	0.053	0.11	0.34	13	-0.25	15	28
CARD11	-0.011	0.12	0.22	8	-0.36	40	48
FCGR2B	0.03	0.019	-10000	0	0	158	158
PPP3CA	0.037	0.013	-10000	0	0	63	63
BCL10	0.041	0.006	-10000	0	0	12	12
IKK complex	0.018	0.052	0.16	14	-0.12	11	25
PTPRC	0.025	0.021	-10000	0	0	227	227
PDPK1	0.014	0.082	0.19	48	-0.16	9	57
PPP3CB	0.04	0.009	-10000	0	0	30	30
PPP3CC	0.033	0.017	-10000	0	0	114	114
POU2F2	0.013	0.043	0.12	2	-0.084	41	43

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.016	0.16	-10000	0	-0.44	53	53
HDAC1	0.043	0.025	0.084	105	-0.003	59	164
AES	0.038	0.016	0.08	15	0	71	86
FBXW11	0.04	0.008	-10000	0	0	23	23
DTX1	0.041	0.005	-10000	0	0	9	9
LRP6/FZD1	0.041	0.049	-10000	0	-0.14	31	31
TLE1	0.039	0.015	0.076	13	-0.001	53	66
AP1	-0.007	0.084	0.15	1	-0.18	93	94
NCSTN	0.04	0.008	-10000	0	0	21	21
ADAM10	0.039	0.011	-10000	0	0	39	39
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.066	0.21	-10000	0	-0.61	50	50
NICD/RBPSUH	-0.011	0.14	-10000	0	-0.44	53	53
WIF1	0.039	0.01	-10000	0	0	31	31
NOTCH1	-0.004	0.15	-10000	0	-0.46	52	52
PSENEN	0.035	0.015	-10000	0	0	88	88
KREMEN2	0.04	0.009	-10000	0	0	26	26
DKK1	0.039	0.011	-10000	0	0	41	41
beta catenin/beta TrCP1	0.017	0.091	0.31	1	-0.33	13	14
APH1B	0.035	0.015	-10000	0	0	86	86
APH1A	0.041	0.006	-10000	0	0	11	11
AXIN1	0.003	0.061	-10000	0	-0.32	4	4
CtBP/CBP/TCF1/TLE1/AES	0.013	0.095	0.18	75	-0.18	48	123
PSEN1	0.039	0.01	-10000	0	0	34	34
FOS	0.026	0.02	-10000	0	0	205	205
JUN	0.036	0.015	-10000	0	0	80	80
MAP3K7	0.041	0.015	0.068	14	0	47	61
CTNNB1	0	0.085	0.3	1	-0.32	14	15
MAPK3	0.041	0.007	-10000	0	0	17	17
DKK2/LRP6/Kremen 2	0.056	0.053	-10000	0	-0.12	28	28
HNF1A	0.002	0.008	0.037	18	-10000	0	18
CTBP1	0.039	0.016	0.079	18	-0.001	59	77
MYC	-0.15	0.42	-10000	0	-1.2	73	73
NKD1	0.039	0.012	-10000	0	0	50	50
FZD1	0.04	0.007	-10000	0	0	17	17
NOTCH1 precursor/Deltex homolog 1	0.015	0.16	-10000	0	-0.44	54	54
apoptosis	-0.006	0.083	0.15	1	-0.18	93	94
Delta 1/NOTCHprecursor	0.011	0.15	-10000	0	-0.44	53	53
DLL1	0.037	0.013	-10000	0	0	60	60
PPARD	0.009	0.076	-10000	0	-1	2	2
Gamma Secretase	0.071	0.087	-10000	0	-0.12	68	68
APC	-0.02	0.12	-10000	0	-0.42	32	32
DVL1	0.019	0.058	-10000	0	-0.27	16	16
CSNK2A1	0.038	0.011	-10000	0	0	40	40
MAP3K7IP1	0.041	0.015	0.068	15	0	51	66
DKK1/LRP6/Kremen 2	0.056	0.053	-10000	0	-0.12	27	27
LRP6	0.034	0.016	-10000	0	0	103	103
CSNK1A1	0.039	0.009	-10000	0	0	24	24
NLK	0.026	0.043	-10000	0	-0.22	12	12
CCND1	-0.16	0.44	-10000	0	-1.2	82	82
WNT1	0.041	0.007	-10000	0	0	15	15
Axin1/APC/beta catenin	0.002	0.1	0.27	3	-0.35	20	23
DKK2	0.038	0.012	-10000	0	0	49	49
NOTCH1 precursor/DVL1	0.014	0.15	-10000	0	-0.39	54	54
GSK3B	0.04	0.01	-10000	0	0	29	29
FRAT1	0.041	0.01	-10000	0	0	25	25
NOTCH/Deltex homolog 1	0.021	0.16	-10000	0	-0.44	54	54
PPP2R5D	0.021	0.054	-10000	0	-0.29	12	12
MAPK1	0.039	0.011	-10000	0	0	43	43
WNT1/LRP6/FZD1	0.075	0.061	-10000	0	-0.11	30	30
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.03	0.024	-10000	0	-0.017	82	82

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.014	0.17	-10000	0	-0.87	13	13
UGCG	-0.006	0.15	-10000	0	-0.7	20	20
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.02	0.18	0.3	2	-0.39	71	73
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.004	0.14	-10000	0	-0.69	20	20
mol:DAG	-0.007	0.031	0.17	15	-10000	0	15
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.037	0.22	0.37	1	-0.48	84	85
FRAP1	-0.055	0.26	0.39	1	-0.56	85	86
FOXO3	-0.053	0.25	0.29	3	-0.52	94	97
AKT1	-0.062	0.28	0.26	2	-0.57	94	96
GAB2	0.029	0.021	-10000	0	-0.003	155	155
SMPD1	0	0.12	-10000	0	-0.58	19	19
SGMS1	-0.003	0.038	0.063	10	-0.078	78	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	51	51
CALM1	0.04	0.009	-10000	0	0	30	30
cell proliferation	0.005	0.18	0.26	9	-0.33	75	84
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	-0.84	27	27
mol:sphingomyelin	-0.007	0.031	0.17	15	-10000	0	15
natural killer cell activation	-0.001	0.004	-10000	0	-0.013	38	38
JAK3	0.035	0.022	-10000	0	-0.046	22	22
PIK3R1	0.031	0.024	-10000	0	-0.04	26	26
JAK1	0.037	0.02	-10000	0	-0.043	22	22
NFKB1	0.035	0.015	-10000	0	0	85	85
MYC	-0.03	0.35	0.42	8	-0.82	75	83
MYB	-0.048	0.3	-10000	0	-1.1	42	42
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.027	0.17	0.25	3	-0.36	88	91
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.005	0.19	-10000	0	-0.78	27	27
mol:PI-3-4-5-P3	-0.025	0.17	0.27	4	-0.35	88	92
Rac1/GDP	0.008	0.045	-10000	0	-0.12	45	45
T cell proliferation	-0.028	0.16	0.25	4	-0.34	87	91
SHC1	0.037	0.016	-10000	0	-0.013	48	48
RAC1	0.039	0.01	-10000	0	0	35	35
positive regulation of cyclin-dependent protein kinase activity	0.001	0.02	0.032	40	-0.064	40	80
PRKCZ	-0.031	0.17	0.25	4	-0.35	88	92
NF kappa B1 p50/RelA	-0.03	0.24	0.4	1	-0.49	84	85
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.004	0.12	-10000	0	-0.34	41	41
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
IL2RA	0.036	0.018	-10000	0	-0.009	68	68
IL2RB	0.034	0.022	-10000	0	-0.045	22	22
TERT	0.037	0.014	-10000	0	0	67	67
E2F1	-0.003	0.13	-10000	0	-0.41	43	43
SOS1	0.035	0.018	-10000	0	-0.008	77	77
RPS6	0.038	0.011	-10000	0	0	44	44
mol:cAMP	-0.001	0.01	0.032	37	-0.017	39	76
PTPN11	0.035	0.02	-10000	0	-0.017	62	62
IL2RG	0.025	0.026	-10000	0	-0.041	28	28
actin cytoskeleton organization	-0.028	0.16	0.25	4	-0.34	87	91
GRB2	0.038	0.016	-10000	0	-0.019	35	35
IL2	0.035	0.024	-10000	0	-0.04	36	36
PIK3CA	0.028	0.024	-10000	0	-0.043	22	22
Rac1/GTP	0.032	0.062	-10000	0	-0.11	44	44
LCK	0.036	0.023	-10000	0	-0.04	37	37
BCL2	-0.032	0.2	0.4	1	-0.52	51	52

×

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

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
BAG4	0.037	0.013	-10000	0	0	63	63
Caspase 8 (4 units)	0.035	0.094	-10000	0	-0.24	28	28
NEF	0.003	0.005	-10000	0	-0.1	1	1
NFKBIA	0.026	0.042	0.084	6	-0.068	78	84
BIRC3	-0.057	0.1	0.2	4	-0.28	87	91
CYCS	-0.006	0.069	0.19	11	-0.25	18	29
RIPK1	0.038	0.012	-10000	0	0	48	48
CD247	0.003	0.005	-10000	0	-0.1	1	1
MAP2K7	-0.008	0.17	-10000	0	-0.56	37	37
protein ubiquitination	-0.001	0.098	0.23	7	-0.26	34	41
CRADD	0.041	0.006	-10000	0	0	12	12
DAXX	0.04	0.007	-10000	0	0	18	18
FAS	0.034	0.016	-10000	0	0	98	98
BID	0.002	0.064	0.16	3	-0.17	51	54
NF-kappa-B/RelA/I kappa B alpha	0.028	0.11	-10000	0	-0.18	116	116
TRADD	0.036	0.014	-10000	0	0	76	76
MAP3K5	0.037	0.014	-10000	0	0	70	70
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	0.028	0.11	-10000	0	-0.18	116	116
MAPK8	-0.012	0.16	-10000	0	-0.53	35	35
APAF1	0.039	0.01	-10000	0	0	33	33
TRAF1	0.04	0.008	-10000	0	0	19	19
TRAF2	0.04	0.009	-10000	0	0	25	25
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.067	-10000	0	-0.17	56	56
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.006	0.11	-10000	0	-0.32	34	34
CHUK	-0.003	0.1	0.24	7	-0.29	33	40
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.075	0.085	-10000	0	-0.13	58	58
TCRz/NEF	0.01	0.008	-10000	0	-0.17	1	1
TNF	0.04	0.009	-10000	0	0	25	25
FASLG	0.022	0.014	-10000	0	-0.3	1	1
NFKB1	0.027	0.041	0.084	7	-0.071	64	71
TNFR1A/BAG4/TNF-alpha	0.059	0.046	-10000	0	-0.12	15	15
CASP6	-0.047	0.23	-10000	0	-0.53	89	89
CASP7	-0.045	0.2	0.3	7	-0.4	109	116
RELA	0.027	0.044	0.08	7	-0.066	95	102
CASP2	0.038	0.012	-10000	0	0	48	48
CASP3	-0.057	0.2	0.31	6	-0.41	114	120
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
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	0.006	0.11	0.24	8	-0.3	30	38
APAF-1/Caspase 9	-0.027	0.11	0.18	2	-0.25	91	93
BCL2	-0.014	0.14	-10000	0	-0.49	34	34

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.026	0.2	-10000	0	-0.72	36	36
epithelial cell differentiation	-0.027	0.19	-10000	0	-0.66	36	36
ITCH	0.039	0.038	0.1	8	-0.097	28	36
WWP1	-0.063	0.27	-10000	0	-1.1	32	32
FYN	0.034	0.016	-10000	0	0	102	102
EGFR	0.036	0.014	-10000	0	0	73	73
PRL	0.039	0.011	-10000	0	0	39	39
neuron projection morphogenesis	-0.043	0.16	0.22	17	-0.57	34	51
PTPRZ1	0.039	0.01	-10000	0	0	36	36
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.006	0.18	0.28	2	-0.61	35	37
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.033	0.18	-10000	0	-0.65	37	37
ADAM17	0.038	0.035	0.098	4	-0.087	25	29
ErbB4/ErbB4	-0.05	0.21	-10000	0	-0.78	36	36
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.029	0.2	-10000	0	-0.71	36	36
NCOR1	0.038	0.013	-10000	0	0	57	57
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.027	0.18	-10000	0	-0.58	41	41
GRIN2B	-0.033	0.16	0.24	5	-0.54	41	46
ErbB4/ErbB2/betacellulin	-0.028	0.18	-10000	0	-0.63	38	38
STAT1	0.034	0.017	-10000	0	0	108	108
HBEGF	0.04	0.009	-10000	0	0	29	29
PRLR	0.035	0.015	-10000	0	0	84	84
E4ICDs/ETO2	-0.03	0.2	-10000	0	-0.72	36	36
axon guidance	-0.054	0.22	-10000	0	-0.81	38	38
NEDD4	0.038	0.039	0.1	7	-0.087	36	43
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	-0.02	0.18	-10000	0	-0.63	37	37
MAPK3	-0.024	0.16	0.27	9	-0.57	35	44
STAT1 (dimer)	-0.034	0.21	-10000	0	-0.73	37	37
MAPK1	-0.024	0.16	0.27	9	-0.58	35	44
JAK2	0.034	0.017	-10000	0	0	108	108
ErbB4/ErbB2/neuregulin 1 beta	-0.031	0.17	0.2	2	-0.64	36	38
NRG1	-0.007	0.032	0.042	24	-0.11	20	44
NRG3	0.035	0.016	-10000	0	0	91	91
NRG2	0.041	0.006	-10000	0	0	12	12
NRG4	0.029	0.019	-10000	0	0	168	168
heart development	-0.054	0.22	-10000	0	-0.81	38	38
neural crest cell migration	-0.031	0.17	0.2	2	-0.63	36	38
ERBB2	-0.008	0.032	0.036	117	-0.1	24	141
WWOX/E4ICDs	-0.028	0.2	-10000	0	-0.72	36	36
SHC1	0.04	0.009	-10000	0	0	29	29
ErbB4/EGFR/neuregulin 4	-0.036	0.2	-10000	0	-0.7	36	36
apoptosis	0.03	0.19	0.62	43	-10000	0	43
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.025	0.2	-10000	0	-0.72	36	36
ErbB4/ErbB2/epiregulin	-0.02	0.18	-10000	0	-0.63	37	37
ErbB4/ErbB4/betacellulin/betacellulin	-0.034	0.2	-10000	0	-0.73	36	36
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.003	0.19	-10000	0	-0.63	35	35
MDM2	-0.042	0.19	0.27	8	-0.72	33	41
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.02	0.16	-10000	0	-0.57	37	37
STAT5A	-0.055	0.22	-10000	0	-0.8	37	37
ErbB4/EGFR/neuregulin 1 beta	-0.026	0.18	-10000	0	-0.62	37	37
DLG4	0.04	0.009	-10000	0	0	29	29
GRB2/SHC	0.057	0.022	-10000	0	-0.14	4	4
E4ICDs/TAB2/NCoR1	-0.019	0.2	-10000	0	-0.68	38	38
STAT5A (dimer)	-0.023	0.21	-10000	0	-0.74	36	36
MAP3K7IP2	0.037	0.013	-10000	0	0	63	63
STAT5B (dimer)	-0.036	0.23	-10000	0	-0.77	39	39
LRIG1	0.033	0.017	-10000	0	0	118	118
EREG	0.038	0.012	-10000	0	0	48	48
BTC	0.033	0.017	-10000	0	0	113	113
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.058	0.23	-10000	0	-0.8	40	40
ERBB4	-0.049	0.21	-10000	0	-0.84	33	33
STAT5B	0.039	0.011	-10000	0	0	41	41
YAP1	0.007	0.1	-10000	0	-0.52	17	17
GRB2	0.041	0.007	-10000	0	0	14	14
ErbB4/ErbB2/neuregulin 4	-0.032	0.18	-10000	0	-0.64	37	37
glial cell differentiation	0.019	0.2	0.67	38	-10000	0	38
WWOX	0.037	0.014	-10000	0	0	69	69
cell proliferation	-0.07	0.21	0.28	1	-0.61	57	58

×

Caspase cascade in apoptosis

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
TOP1	-0.015	0.14	0.26	3	-0.32	61	64
ACTA1	0.004	0.086	0.21	13	-0.25	15	28
NUMA1	-0.018	0.14	0.26	3	-0.31	61	64
SPTAN1	-0.002	0.085	0.23	7	-0.25	15	22
LIMK1	0.001	0.085	0.22	10	-0.25	15	25
BIRC3	0.026	0.02	-10000	0	0	213	213
BIRC2	0.036	0.014	-10000	0	0	73	73
BAX	0.04	0.008	-10000	0	0	20	20
CASP10	-0.011	0.025	0.057	54	-10000	0	54
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.037	0.17	0.26	3	-0.41	62	65
DIABLO	0.037	0.013	-10000	0	0	64	64
apoptotic nuclear changes	-0.002	0.085	0.23	7	-0.25	14	21
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.041	0.006	-10000	0	0	12	12
GSN	-0.003	0.085	0.24	7	-0.26	14	21
MADD	0.041	0.006	-10000	0	0	12	12
TFAP2A	-0.031	0.21	-10000	0	-0.6	49	49
BID	0.006	0.034	0.13	20	-0.094	25	45
MAP3K1	-0.029	0.14	-10000	0	-0.37	71	71
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	0.042	-10000	0	-0.15	20	20
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.1	0.24	39	-0.24	22	61
CASP9	0.04	0.009	-10000	0	0	26	26
DNA repair	-0.012	0.08	0.27	24	-0.16	13	37
neuron apoptosis	-0.035	0.2	-10000	0	-0.63	46	46
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.016	0.12	0.24	7	-0.31	36	43
APAF1	0.039	0.01	-10000	0	0	33	33
CASP6	-0.11	0.34	-10000	0	-0.85	91	91
TRAF2	0.04	0.009	-10000	0	0	25	25
ICAD/CAD	-0.001	0.084	0.24	11	-0.25	11	22
CASP7	0.013	0.11	0.19	77	-0.28	23	100
KRT18	-0.016	0.15	-10000	0	-0.62	23	23
apoptosis	-0.043	0.16	0.24	9	-0.37	81	90
DFFA	0.002	0.083	0.21	11	-0.24	14	25
DFFB	0.002	0.085	0.23	11	-0.25	14	25
PARP1	0.012	0.081	0.16	13	-0.27	24	37
actin filament polymerization	0.004	0.083	0.26	10	-0.24	12	22
TNF	0.04	0.009	-10000	0	0	25	25
CYCS	0.001	0.07	0.16	12	-0.21	33	45
SATB1	-0.11	0.32	-10000	0	-0.81	91	91
SLK	-0.002	0.085	0.22	10	-0.25	16	26
p15 BID/BAX	0.032	0.05	0.16	3	-0.3	4	7
CASP2	0.005	0.087	0.24	18	-0.24	29	47
JNK cascade	0.029	0.14	0.37	71	-10000	0	71
CASP3	0.006	0.089	0.23	10	-0.26	15	25
LMNB2	-0.051	0.21	0.25	4	-0.42	99	103
RIPK1	0.038	0.012	-10000	0	0	48	48
CASP4	0.034	0.017	-10000	0	0	107	107
Mammalian IAPs/DIABLO	0.014	0.09	-10000	0	-0.13	127	127
negative regulation of DNA binding	-0.03	0.2	-10000	0	-0.59	49	49
stress fiber formation	-0.003	0.084	0.21	10	-0.24	16	26
GZMB	-0.016	0.009	0	131	-10000	0	131
CASP1	-0.011	0.069	-10000	0	-0.2	66	66
LMNB1	-0.05	0.2	0.26	5	-0.41	85	90
APP	-0.036	0.2	-10000	0	-0.64	46	46
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.01	0.002	0	28	-10000	0	28
VIM	-0.038	0.17	0.25	10	-0.38	82	92
LMNA	-0.019	0.15	0.26	4	-0.35	62	66
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.006	0.085	-10000	0	-0.24	35	35
LRDD	0.039	0.01	-10000	0	0	34	34
SREBF1	0	0.084	0.22	8	-0.26	13	21
APAF-1/Caspase 9	0.026	0.15	-10000	0	-0.65	21	21
nuclear fragmentation during apoptosis	-0.018	0.13	0.26	3	-0.31	61	64
CFL2	-0.004	0.084	0.24	12	-0.26	11	23
GAS2	0.004	0.088	0.22	20	-0.25	15	35
positive regulation of apoptosis	-0.044	0.19	0.26	4	-0.39	96	100
PRF1	0.037	0.013	-10000	0	0	60	60

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.14	0.36	1	-0.61	14	15
CRKL	0.028	0.089	0.18	122	-0.16	1	123
mol:DAG	0.044	0.073	0.23	3	-0.23	15	18
HRAS	0.022	0.099	0.25	43	-0.18	3	46
MAPK8	0.014	0.08	0.18	87	-0.14	2	89
RAP1A	0.027	0.088	0.18	121	-0.17	2	123
GAB1	0.025	0.086	0.18	113	-0.16	1	114
MAPK14	0.015	0.083	0.18	90	-0.14	2	92
EPO	0.046	0.016	0.083	6	-0.037	8	14
PLCG1	0.044	0.074	0.23	3	-0.24	15	18
EPOR/TRPC2/IP3 Receptors	0.04	0.019	0.087	4	-0.036	6	10
RAPGEF1	0.04	0.008	-10000	0	0	22	22
EPO/EPOR (dimer)/SOCS3	0.064	0.051	-10000	0	-0.13	16	16
GAB1/SHC/GRB2/SOS1	0.072	0.083	0.24	36	-0.16	6	42
EPO/EPOR (dimer)	0.057	0.032	-10000	0	-0.15	2	2
IRS2	0.027	0.088	0.18	118	-0.16	1	119
STAT1	0.035	0.095	0.25	3	-0.26	23	26
STAT5B	0.047	0.076	0.24	3	-0.21	19	22
cell proliferation	0.008	0.079	0.17	90	-0.13	2	92
GAB1/SHIP/PIK3R1/SHP2/SHC	0.036	0.061	0.16	2	-0.15	5	7
TEC	0.02	0.083	0.18	101	-0.17	8	109
SOCS3	0.037	0.014	-10000	0	0	67	67
STAT1 (dimer)	0.035	0.093	0.25	3	-0.25	23	26
JAK2	0.038	0.021	0.082	7	-0.036	4	11
PIK3R1	0.034	0.016	-10000	0	0	106	106
EPO/EPOR (dimer)/JAK2	0.065	0.069	0.24	29	-0.1	27	56
EPO/EPOR	0.057	0.032	-10000	0	-0.15	2	2
LYN	0.036	0.018	-10000	0	-0.036	9	9
TEC/VAV2	0.035	0.078	0.22	28	-0.16	11	39
elevation of cytosolic calcium ion concentration	0.04	0.019	0.087	4	-0.036	6	10
SHC1	0.04	0.009	-10000	0	0	29	29
EPO/EPOR (dimer)/LYN	0.062	0.061	-10000	0	-0.12	28	28
mol:IP3	0.044	0.073	0.23	3	-0.23	15	18
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.046	0.074	0.19	75	-0.13	4	79
SH2B3	0	0.008	0.032	12	-10000	0	12
NFKB1	0.011	0.077	0.19	73	-0.18	5	78
EPO/EPOR (dimer)/JAK2/SOCS3	0.013	0.05	0.21	2	-0.16	30	32
PTPN6	0.036	0.068	0.18	79	-0.1	26	105
TEC/VAV2/GRB2	0.053	0.086	0.23	32	-0.17	11	43
EPOR	0.04	0.019	0.087	4	-0.036	6	10
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.071	0.082	0.24	35	-0.16	6	41
SOS1	0.038	0.013	-10000	0	0	57	57
PLCG2	0.036	0.015	-10000	0	0	83	83
CRKL/CBL/C3G	0.073	0.078	0.24	41	-0.15	4	45
VAV2	0.026	0.088	0.18	115	-0.16	2	117
CBL	0.028	0.091	0.18	126	-0.23	1	127
SHC/Grb2/SOS1	0.037	0.056	0.17	1	-0.13	13	14
STAT5A	0.046	0.079	0.24	3	-0.22	19	22
GRB2	0.041	0.007	-10000	0	0	14	14
STAT5 (dimer)	0.062	0.091	0.28	3	-0.28	13	16
LYN/PLCgamma2	0.038	0.05	-10000	0	-0.13	33	33
PTPN11	0.04	0.009	-10000	0	0	29	29
BTK	0.027	0.089	0.18	120	-0.17	6	126
BCL2	0.031	0.12	0.36	1	-0.46	11	12

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	52	52
epithelial cell differentiation	0.056	0.068	-10000	0	-0.13	51	51
CYFIP2	0.038	0.011	-10000	0	0	45	45
ENAH	-0.034	0.072	0.24	9	-0.2	7	16
EGFR	0.036	0.014	-10000	0	0	73	73
EPHA2	0.039	0.01	-10000	0	0	34	34
MYO6	-0.03	0.048	0.18	8	-0.21	17	25
CTNNB1	0.039	0.01	-10000	0	0	32	32
ABI1/Sra1/Nap1	0.061	0.058	-10000	0	-0.12	39	39
AQP5	-0.076	0.14	0.18	3	-0.36	99	102
CTNND1	0.041	0.007	-10000	0	0	17	17
mol:PI-4-5-P2	-0.03	0.044	0.18	7	-0.2	12	19
regulation of calcium-dependent cell-cell adhesion	-0.028	0.045	0.19	8	-0.2	12	20
EGF	0.038	0.012	-10000	0	0	52	52
NCKAP1	0.039	0.01	-10000	0	0	33	33
AQP3	-0.023	0.057	0.18	2	-0.29	14	16
cortical microtubule organization	0.056	0.068	-10000	0	-0.13	51	51
GO:0000145	-0.029	0.04	0.16	7	-0.19	12	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.063	0.072	-10000	0	-0.13	51	51
MLLT4	0.033	0.017	-10000	0	0	110	110
ARF6/GDP	-0.051	0.048	-10000	0	-0.15	63	63
ARF6	0.04	0.007	-10000	0	0	18	18
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.077	-10000	0	-0.12	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.016	0.05	0.21	6	-0.21	14	20
PVRL2	0.039	0.011	-10000	0	0	43	43
ZYX	-0.027	0.042	0.19	7	-0.2	8	15
ARF6/GTP	0.067	0.083	-10000	0	-0.12	62	62
CDH1	0.035	0.016	-10000	0	0	96	96
EGFR/EGFR/EGF/EGF	0.037	0.075	-10000	0	-0.13	65	65
RhoA/GDP	0.056	0.072	-10000	0	-0.12	54	54
actin cytoskeleton organization	-0.032	0.049	0.16	7	-0.23	17	24
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	116	116
GIT1	0.04	0.008	-10000	0	0	23	23
IGF1R	0.033	0.017	-10000	0	0	116	116
IGF1	0.036	0.015	-10000	0	0	82	82
DIAPH1	-0.002	0.22	-10000	0	-0.58	58	58
Wnt receptor signaling pathway	-0.056	0.068	0.13	51	-10000	0	51
RHOA	0.041	0.007	-10000	0	0	14	14
RhoA/GTP	-0.051	0.047	-10000	0	-0.14	85	85
CTNNA1	0.039	0.01	-10000	0	0	36	36
VCL	-0.033	0.05	0.16	7	-0.23	17	24
EFNA1	0.034	0.016	-10000	0	0	101	101
LPP	-0.029	0.044	0.18	7	-0.2	14	21
Ephrin A1/EPHA2	0.032	0.077	-10000	0	-0.13	75	75
SEC6/SEC8	-0.045	0.043	-10000	0	-0.14	63	63
MGAT3	-0.029	0.046	0.19	8	-0.2	12	20
HGF/MET	0.016	0.087	-10000	0	-0.12	124	124
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	52	52
actin cable formation	0.002	0.098	0.26	25	-0.24	16	41
KIAA1543	-0.033	0.043	0.16	7	-0.2	13	20
KIFC3	-0.032	0.042	0.18	6	-0.2	12	18
NCK1	0.036	0.014	-10000	0	0	77	77
EXOC3	0.041	0.005	-10000	0	0	7	7
ACTN1	-0.031	0.05	0.19	9	-0.21	16	25
NCK1/GIT1	0.044	0.047	-10000	0	-0.14	30	30
mol:GDP	0.056	0.068	-10000	0	-0.13	51	51
EXOC4	0.038	0.012	-10000	0	0	51	51
STX4	-0.029	0.034	0.035	8	-0.12	51	59
PIP5K1C	-0.03	0.044	0.18	7	-0.2	12	19
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.04	0.009	-10000	0	0	28	28
ROCK1	-0.027	0.086	0.27	10	-0.23	6	16
adherens junction assembly	-0.053	0.14	-10000	0	-0.42	44	44
IGF-1R heterotetramer/IGF1	0.024	0.082	-10000	0	-0.13	96	96
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.05	-10000	0	-0.14	31	31
MET	0.027	0.02	-10000	0	0	195	195
PLEKHA7	-0.031	0.046	0.18	8	-0.2	14	22
mol:GTP	0.059	0.075	-10000	0	-0.12	61	61
establishment of epithelial cell apical/basal polarity	-0.037	0.056	0.13	27	-0.21	14	41
cortical actin cytoskeleton stabilization	0.003	0.07	-10000	0	-0.19	52	52
regulation of cell-cell adhesion	-0.032	0.049	0.16	7	-0.23	17	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.003	0.07	-10000	0	-0.19	52	52

×

Circadian rhythm 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
chromatin modification	-0.049	0.3	-10000	0	-1	48	48
CLOCK	0.031	0.031	-10000	0	-0.069	40	40
TIMELESS/CRY2	-0.05	0.31	-10000	0	-1	48	48
DEC1/BMAL1	0.044	0.048	-10000	0	-0.14	20	20
ATR	0.035	0.016	-10000	0	0	92	92
NR1D1	-0.017	0.11	-10000	0	-0.46	9	9
ARNTL	0.032	0.031	-10000	0	-0.068	42	42
TIMELESS	-0.081	0.32	-10000	0	-1.1	48	48
NPAS2	0.027	0.031	-10000	0	-0.068	37	37
CRY2	0.041	0.004	-10000	0	0	6	6
mol:CO	0.001	0.041	0.13	48	-10000	0	48
CHEK1	0.033	0.017	-10000	0	0	118	118
mol:HEME	-0.001	0.041	-10000	0	-0.13	48	48
PER1	0.039	0.01	-10000	0	0	36	36
BMAL/CLOCK/NPAS2	0.033	0.096	-10000	0	-0.14	112	112
BMAL1/CLOCK	-0.041	0.2	-10000	0	-0.59	50	50
S phase of mitotic cell cycle	-0.049	0.3	-10000	0	-1	48	48
TIMELESS/CHEK1/ATR	-0.051	0.31	-10000	0	-1.1	48	48
mol:NADPH	-0.001	0.041	-10000	0	-0.13	48	48
PER1/TIMELESS	-0.053	0.31	-10000	0	-1	48	48
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.04	0.008	-10000	0	0	23	23

×

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	0.011	-10000	0	-10000	0	0
ARNO/beta Arrestin1-2	0.044	0.031	-10000	0	-0.088	9	9
EGFR	0.036	0.014	-10000	0	0	73	73
EPHA2	0.039	0.01	-10000	0	0	34	34
USP6	0.04	0.009	-10000	0	0	30	30
IQSEC1	0.041	0.007	-10000	0	0	17	17
EGFR/EGFR/EGF/EGF	0.04	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	10	10
ARRB1	0.038	0.012	-10000	0	0	47	47
FBXO8	0.037	0.014	-10000	0	0	70	70
TSHR	0.037	0.013	-10000	0	0	60	60
EGF	0.038	0.012	-10000	0	0	52	52
somatostatin receptor activity	0	0	0	6	-0.001	43	49
ARAP2	0	0	0	11	0	36	47
mol:GDP	0.012	0.073	0.15	3	-0.18	40	43
mol:PI-3-4-5-P3	0	0	0	7	0	37	44
ITGA2B	0.04	0.009	-10000	0	0	29	29
ARF6	0.041	0.007	-10000	0	0	18	18
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.077	-10000	0	-0.12	61	61
ADAP1	0	0	0	6	0	24	30
KIF13B	0.033	0.017	-10000	0	0	111	111
HGF/MET	0.013	0.075	-10000	0	-0.14	104	104
PXN	0.041	0.007	-10000	0	0	14	14
ARF6/GTP	0.014	0.083	0.19	5	-0.21	42	47
EGFR/EGFR/EGF/EGF/ARFGEP100	0.059	0.054	-10000	0	-0.12	35	35
ADRB2	0.041	0.006	-10000	0	0	11	11
receptor agonist activity	0	0	0	9	0	36	45
actin filament binding	0	0	0	5	0	45	50
SRC	0.039	0.01	-10000	0	0	31	31
ITGB3	0.033	0.017	-10000	0	0	120	120
GNAQ	0.038	0.012	-10000	0	0	50	50
EFA6/PI-4-5-P2	0	0	0.001	12	-0.001	35	47
ARF6/GDP	0.011	0.076	0.2	8	-0.24	25	33
ARF6/GDP/GULP/ACAP1	0.027	0.086	-10000	0	-0.2	35	35
alphaIIb/beta3 Integrin/paxillin/GIT1	0.081	0.058	-10000	0	-0.11	34	34
ACAP1	0	0	0	3	0	1	4
ACAP2	0	0	0	5	0	36	41
LHCGR/beta Arrestin2	0.032	0.024	-10000	0	-0.065	26	26
EFNA1	0.034	0.016	-10000	0	0	101	101
HGF	0.04	0.009	-10000	0	0	29	29
CYTH3	0	0	0.001	10	-0.001	35	45
CYTH2	0	0.001	0.003	4	-0.004	39	43
NCK1	0.036	0.014	-10000	0	0	77	77
fibronectin binding	0	0	0	9	0	36	45
endosomal lumen acidification	0	0	0	9	0	21	30
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.032	0.018	-10000	0	0	130	130
GNAQ/ARNO	0.026	0.009	-10000	0	0	50	50
mol:Phosphatidic acid	0	0	0	5	0	36	41
PIP3-E	0.038	0.013	-10000	0	0	57	57
MET	0.027	0.02	-10000	0	0	195	195
GNA14	0.039	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GIT1	0.04	0.008	-10000	0	0	23	23
mol:PI-4-5-P2	0	0	0.001	13	-0.001	40	53
GNA11	0.037	0.013	-10000	0	0	63	63
LHCGR	0.04	0.009	-10000	0	0	25	25
AGTR1	0.037	0.014	-10000	0	0	69	69
desensitization of G-protein coupled receptor protein signaling pathway	0.032	0.024	-10000	0	-0.065	26	26
IPCEF1/ARNO	0.053	0.045	-10000	0	-0.087	34	34
alphaIIb/beta3 Integrin	0.039	0.05	-10000	0	-0.14	34	34

×

Aurora B signaling

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
Condensin I complex	-0.007	0.038	-10000	0	-0.12	56	56
STMN1	-0.011	0.016	0.03	11	-10000	0	11
Aurora B/RasGAP/Survivin	0.046	0.074	-10000	0	-0.16	49	49
Chromosomal passenger complex/Cul3 protein complex	-0.005	0.091	-10000	0	-0.25	44	44
BIRC5	0.037	0.015	-10000	0	-0.002	62	62
DES	-0.04	0.27	-10000	0	-0.81	57	57
Aurora C/Aurora B/INCENP	0.064	0.047	-10000	0	-0.12	27	27
Aurora B/TACC1	0.037	0.04	-10000	0	-0.1	28	28
Aurora B/PP2A	0.044	0.049	-10000	0	-0.14	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.01	0.062	-10000	0	-0.16	74	74
mitotic metaphase/anaphase transition	0.002	0.006	0.013	106	-10000	0	106
NDC80	-0.004	0.01	0.02	10	-10000	0	10
Cul3 protein complex	0.049	0.06	-10000	0	-0.12	42	42
KIF2C	-0.057	0.19	-10000	0	-0.49	79	79
PEBP1	-0.001	0.003	-10000	0	-0.011	36	36
KIF20A	0.032	0.018	-10000	0	0	132	132
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.036	0.057	-10000	0	-0.14	44	44
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	-0.035	0.19	-10000	0	-0.56	57	57
PSMA3	0.038	0.012	-10000	0	0	54	54
G2/M transition of mitotic cell cycle	-0.001	0.003	0.009	29	-0.008	16	45
H3F3B	0.002	0.056	-10000	0	-0.2	39	39
AURKB	0.038	0.016	-10000	0	0	76	76
AURKC	0.042	0.002	-10000	0	0	1	1
CDCA8	0.036	0.016	-10000	0	-0.004	71	71
cytokinesis	-0.03	0.18	0.2	1	-0.44	67	68
Aurora B/Septin1	-0.003	0.19	0.22	1	-0.38	80	81
AURKA	-0.001	0.003	0.009	29	-0.008	16	45
INCENP	0.039	0.016	-10000	0	-0.029	27	27
KLHL13	0.033	0.017	-10000	0	0	118	118
BUB1	0.037	0.015	-10000	0	0	74	74
hSgo1/Aurora B/Survivin	0.041	0.078	-10000	0	-0.15	62	62
EVI5	0.039	0.011	-10000	0	0	37	37
RhoA/GTP	0.004	0.17	-10000	0	-0.35	70	70
SGOL1	0.036	0.014	-10000	0	0	73	73
CENPA	-0.014	0.11	-10000	0	-0.3	56	56
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.034	0.064	-10000	0	-0.14	57	57
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.037	0.062	-10000	0	-0.14	54	54
RHOA	0.041	0.007	-10000	0	0	14	14
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	-0.021	0.13	-10000	0	-0.34	66	66
RASA1	0.036	0.014	-10000	0	0	73	73
KLHL9	0.039	0.011	-10000	0	0	43	43
mitotic prometaphase	-0.001	0.003	-10000	0	-0.011	36	36
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.064	-10000	0	-0.14	57	57
PPP1CC	0.039	0.01	-10000	0	0	37	37
Centraspindlin	-0.009	0.17	-10000	0	-0.38	71	71
RhoA/GDP	0.029	0.014	-10000	0	-0.13	4	4
NSUN2	-0.009	0.12	-10000	0	-0.33	61	61
MYLK	0.001	0.057	-10000	0	-0.2	40	40
KIF23	0.035	0.017	-10000	0	0	99	99
VIM	-0.01	0.016	0.041	9	-10000	0	9
RACGAP1	0.037	0.014	-10000	0	-0.004	53	53
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.024	0.12	-10000	0	-0.32	79	79
Chromosomal passenger complex	-0.034	0.14	-10000	0	-0.32	73	73
Chromosomal passenger complex/EVI5	0.066	0.097	-10000	0	-0.17	57	57
TACC1	0.035	0.016	-10000	0	0	91	91
PPP2R5D	0.04	0.009	-10000	0	0	27	27
CUL3	0.04	0.008	-10000	0	0	22	22
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.047	0.04	-10000	0	-0.14	19	19
VLDLR	0.032	0.018	-10000	0	0	129	129
CRKL	0.039	0.01	-10000	0	0	35	35
LRPAP1	0.036	0.015	-10000	0	0	79	79
FYN	0.034	0.016	-10000	0	0	102	102
ITGA3	0.034	0.016	-10000	0	0	101	101
RELN/VLDLR/Fyn	0.032	0.067	-10000	0	-0.13	51	51
MAPK8IP1/MKK7/MAP3K11/JNK1	0.094	0.062	-10000	0	-0.11	18	18
AKT1	-0.001	0.075	-10000	0	-0.17	60	60
MAP2K7	0.038	0.011	-10000	0	0	44	44
RAPGEF1	0.04	0.008	-10000	0	0	22	22
DAB1	0.04	0.009	-10000	0	0	25	25
RELN/LRP8/DAB1	0.059	0.039	-10000	0	-0.1	6	6
LRPAP1/LRP8	0.041	0.053	-10000	0	-0.14	37	37
RELN/LRP8/DAB1/Fyn	0.066	0.056	-10000	0	-0.1	32	32
DAB1/alpha3/beta1 Integrin	0.028	0.083	-10000	0	-0.18	10	10
long-term memory	0.073	0.072	-10000	0	-0.11	30	30
DAB1/LIS1	0.057	0.083	-10000	0	-0.11	58	58
DAB1/CRLK/C3G	0.045	0.073	-10000	0	-0.12	54	54
PIK3CA	0.03	0.019	-10000	0	0	150	150
DAB1/NCK2	0.062	0.083	-10000	0	-0.11	57	57
ARHGEF2	0.039	0.01	-10000	0	0	34	34
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.033	0.017	-10000	0	0	110	110
CDK5R1	0.04	0.009	-10000	0	0	27	27
RELN	0.034	0.016	-10000	0	0	104	104
PIK3R1	0.034	0.016	-10000	0	0	106	106
RELN/LRP8/Fyn	0.045	0.057	-10000	0	-0.12	33	33
GRIN2A/RELN/LRP8/DAB1/Fyn	0.075	0.07	-10000	0	-0.11	33	33
MAPK8	0.04	0.009	-10000	0	0	29	29
RELN/VLDLR/DAB1	0.042	0.054	-10000	0	-0.1	37	37
ITGB1	0.039	0.011	-10000	0	0	39	39
MAP1B	-0.002	0.064	0.22	23	-0.2	5	28
RELN/LRP8	0.049	0.056	-10000	0	-0.12	30	30
GRIN2B/RELN/LRP8/DAB1/Fyn	0.076	0.069	-10000	0	-0.11	28	28
PI3K	0.024	0.062	-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	67	67
RAP1A	-0.004	0.097	0.31	25	-0.18	2	27
PAFAH1B1	0.039	0.011	-10000	0	0	40	40
MAPK8IP1	0.039	0.01	-10000	0	0	31	31
CRLK/C3G	0.056	0.018	-10000	0	-10000	0	0
GRIN2B	0.037	0.014	-10000	0	0	68	68
NCK2	0.041	0.006	-10000	0	0	10	10
neuron differentiation	0.022	0.059	0.17	1	-0.22	7	8
neuron adhesion	-0.012	0.1	0.27	35	-0.25	1	36
LRP8	0.039	0.011	-10000	0	0	39	39
GSK3B	-0.005	0.076	0.18	9	-0.25	15	24
RELN/VLDLR/DAB1/Fyn	0.05	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	-0.17	60	60
CDK5	0.036	0.014	-10000	0	0	77	77
MAPT	-0.009	0.034	0.68	1	-10000	0	1
neuron migration	0.001	0.098	0.25	27	-0.23	17	44
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.021	0.057	0.17	1	-0.22	6	7
RELN/VLDLR	0.052	0.074	-10000	0	-0.11	59	59

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.009	0.054	0.17	50	-0.092	3	53
BUB1B	-0.026	0.083	0.12	1	-0.2	75	76
PLK1	-0.002	0.037	0.076	4	-0.098	42	46
PLK1S1	-0.001	0.02	0.045	5	-0.055	39	44
KIF2A	-0.002	0.033	0.069	3	-0.089	42	45
regulation of mitotic centrosome separation	-0.002	0.037	0.078	3	-0.098	42	45
GOLGA2	0.04	0.009	-10000	0	0	26	26
Hec1/SPC24	-0.01	0.025	-10000	0	-0.08	47	47
WEE1	-0.013	0.089	-10000	0	-0.34	27	27
cytokinesis	-0.038	0.13	0.15	3	-0.28	98	101
PP2A-alpha B56	-0.005	0.25	-10000	0	-0.69	61	61
AURKA	-0.002	0.022	0.049	8	-0.063	33	41
PICH/PLK1	-0.033	0.069	0.073	1	-0.16	108	109
CENPE	-0.008	0.035	0.21	1	-0.13	18	19
RhoA/GTP	0.029	0.014	-10000	0	-0.13	4	4
positive regulation of microtubule depolymerization	-0.002	0.033	0.069	3	-0.088	42	45
PPP2CA	0.04	0.009	-10000	0	0	26	26
FZR1	0.038	0.013	-10000	0	0	57	57
TPX2	-0.025	0.098	-10000	0	-0.24	87	87
PAK1	0.037	0.014	-10000	0	0	66	66
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.008	-10000	0	0	23	23
CLSPN	0.009	0.037	-10000	0	-0.26	7	7
GORASP1	0.041	0.006	-10000	0	0	11	11
metaphase	0	0.004	0.016	12	-0.013	26	38
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.001	0.02	0.045	5	-0.055	39	44
G2 phase of mitotic cell cycle	-0.001	0.003	0.011	15	-10000	0	15
STAG2	0.039	0.01	-10000	0	0	35	35
GRASP65/GM130/RAB1/GTP	0.015	0.071	-10000	0	-0.58	6	6
spindle elongation	-0.002	0.037	0.078	3	-0.098	42	45
ODF2	0.04	0.009	-10000	0	0	27	27
BUB1	-0.043	0.25	-10000	0	-0.73	61	61
TPT1	-0.004	0.055	-10000	0	-0.18	41	41
CDC25C	-0.008	0.089	-10000	0	-0.33	36	36
CDC25B	0.025	0.03	-10000	0	-0.031	104	104
SGOL1	-0.009	0.054	0.093	3	-0.17	50	53
RHOA	0.041	0.007	-10000	0	0	14	14
CCNB1/CDK1	0.005	0.13	-10000	0	-0.21	121	121
CDC14B	-0.01	0.005	0.011	24	-10000	0	24
CDC20	0.034	0.016	-10000	0	0	104	104
PLK1/PBIP1	-0.003	0.032	-10000	0	-0.1	31	31
mitosis	-0.001	0.003	0.013	7	-0.011	7	14
FBXO5	-0.016	0.063	0.11	4	-0.17	59	63
CDC2	0.028	0.022	-10000	0	-0.029	18	18
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.053	-10000	0	-0.25	19	19
ERCC6L	-0.03	0.099	-10000	0	-0.2	119	119
NLP/gamma Tubulin	-0.002	0.032	0.068	2	-0.09	42	44
microtubule cytoskeleton organization	-0.004	0.055	-10000	0	-0.18	41	41
G2/M transition DNA damage checkpoint	0	0.002	0.012	9	-10000	0	9
PPP1R12A	0.04	0.01	-10000	0	0	29	29
interphase	0	0.002	0.012	9	-10000	0	9
PLK1/PRC1-2	0.013	0.083	-10000	0	-0.16	82	82
GRASP65/GM130/RAB1/GTP/PLK1	0.05	0.06	-10000	0	-0.12	31	31
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	0.059	11	-0.068	37	48
mitotic prometaphase	-0.002	0.004	0.018	18	-0.01	3	21
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.069	-10000	0	-0.24	24	24
microtubule-based process	0.014	0.051	-10000	0	-0.14	36	36
Golgi organization	-0.002	0.037	0.078	3	-0.098	42	45
Cohesin/SA2	0.013	0.047	-10000	0	-0.098	59	59
PPP1CB/MYPT1	0.05	0.041	-10000	0	-0.14	21	21
KIF20A	0.032	0.018	-10000	0	0	132	132
APC/C/CDC20	0.016	0.051	-10000	0	-0.13	38	38
PPP2R1A	0.039	0.011	-10000	0	0	42	42
chromosome segregation	-0.003	0.032	-10000	0	-0.1	31	31
PRC1	0.036	0.015	-10000	0	0	82	82
ECT2	0.035	0.11	0.21	136	-0.15	45	181
C13orf34	-0.001	0.029	0.064	7	-0.077	39	46
NUDC	0.002	0.053	-10000	0	-0.25	19	19
regulation of attachment of spindle microtubules to kinetochore	-0.026	0.082	0.12	1	-0.2	75	76
spindle assembly	-0.002	0.034	0.089	3	-0.1	27	30
spindle stabilization	-0.001	0.02	0.045	5	-0.054	39	44
APC/C/HCDH1	0.032	0.014	-10000	0	-0.11	1	1
MKLP2/PLK1	0.014	0.051	-10000	0	-0.14	36	36
CCNB1	0.026	0.027	-10000	0	-0.03	60	60
PPP1CB	0.04	0.01	-10000	0	0	32	32
BTRC	0.04	0.008	-10000	0	0	22	22
ROCK2	-0.006	0.094	-10000	0	-0.33	39	39
TUBG1	-0.002	0.054	-10000	0	-0.2	31	31
G2/M transition of mitotic cell cycle	-0.036	0.1	0.13	12	-0.21	114	126
MLF1IP	-0.008	0.007	0.014	8	-10000	0	8
INCENP	0.041	0.005	-10000	0	0	6	6

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.031	0.18	-10000	0	-0.53	26	26
RAD9A	0.041	0.004	-10000	0	0	6	6
AP1	0.002	0.084	-10000	0	-0.15	114	114
IFNAR2	0.03	0.027	-10000	0	-0.033	70	70
AKT1	0.013	0.038	-10000	0	-0.16	5	5
ER alpha/Oestrogen	0.013	0.043	-10000	0	-0.13	42	42
NFX1/SIN3/HDAC complex	0	0.086	0.17	5	-0.27	30	35
EGF	0.038	0.012	-10000	0	0	52	52
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.044	0.043	-10000	0	-0.12	7	7
TERT/c-Abl	-0.021	0.18	-10000	0	-0.5	27	27
SAP18	0.039	0.01	-10000	0	0	31	31
MRN complex	0.049	0.07	-10000	0	-0.15	48	48
WT1	0.029	0.027	-10000	0	-0.033	67	67
WRN	0.033	0.017	-10000	0	0	119	119
SP1	0.032	0.031	-10000	0	-0.041	78	78
SP3	0.04	0.009	-10000	0	-0.004	18	18
TERF2IP	0.036	0.014	-10000	0	0	73	73
Telomerase/Nucleolin	-0.019	0.18	-10000	0	-0.48	28	28
Mad/Max	0.055	0.024	-10000	0	-0.047	1	1
TERT	-0.034	0.19	-10000	0	-0.55	23	23
CCND1	-0.11	0.37	-10000	0	-0.97	81	81
MAX	0.04	0.009	-10000	0	-0.005	19	19
RBBP7	0.04	0.009	-10000	0	0	25	25
RBBP4	0.038	0.011	-10000	0	0	45	45
TERF2	0.034	0.021	0.094	43	0	78	121
PTGES3	0.038	0.013	-10000	0	0	56	56
SIN3A	0.039	0.01	-10000	0	0	31	31
Telomerase/911	0.024	0.082	-10000	0	-0.28	22	22
CDKN1B	-0.002	0.081	0.2	3	-0.33	21	24
RAD1	0.038	0.013	-10000	0	0	56	56
XRCC5	0.039	0.011	-10000	0	0	38	38
XRCC6	0.037	0.014	-10000	0	0	69	69
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	0.007	-10000	0	-0.004	9	9
JUN	0.035	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	-0.12	9	9
FOS	0.026	0.021	-10000	0	-0.001	209	209
IFN-gamma/IRF1	0.025	0.081	-10000	0	-0.16	80	80
PARP2	0.04	0.009	-10000	0	0	30	30
BLM	0.037	0.014	-10000	0	0	67	67
Telomerase	0.004	0.063	0.13	2	-0.25	20	22
IRF1	0.029	0.04	0.11	1	-0.14	20	21
ESR1	0.035	0.016	-10000	0	0	92	92
KU/TER	0.042	0.054	-10000	0	-0.16	31	31
ATM/TRF2	0.036	0.055	-10000	0	-0.14	40	40
ubiquitin-dependent protein catabolic process	0.002	0.087	0.18	5	-0.28	27	32
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.002	0.089	0.18	5	-0.28	26	31
HDAC1	0.038	0.012	-10000	0	0	54	54
HDAC2	0.029	0.03	-10000	0	-0.04	74	74
ATM	0.009	0.065	-10000	0	-0.24	31	31
SMAD3	-0.013	0.016	0.025	69	-10000	0	69
ABL1	0.039	0.011	-10000	0	0	41	41
MXD1	0.04	0.01	-10000	0	-0.005	20	20
MRE11A	0.038	0.012	-10000	0	0	51	51
HUS1	0.04	0.008	-10000	0	0	20	20
RPS6KB1	0.039	0.01	-10000	0	0	36	36
TERT/NF kappa B1/14-3-3	-0.01	0.19	-10000	0	-0.56	18	18
NR2F2	0.039	0.013	0.07	1	0	38	39
MAPK3	-0.016	0.015	0.022	50	-0.043	2	52
MAPK1	-0.015	0.015	0.022	46	-0.043	2	48
TGFB1/TGF beta receptor Type II	0.037	0.013	-10000	0	0	61	61
NFKB1	0.035	0.015	-10000	0	0	85	85
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	31	31
NBN	0.035	0.016	-10000	0	0	96	96
EGFR	0.036	0.015	-10000	0	0	74	74
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.04	0.052	-10000	0	-0.14	37	37
MYC	0.021	0.021	-10000	0	0	272	272
IL2	0.03	0.031	-10000	0	-0.042	74	74
KU	0.042	0.054	-10000	0	-0.16	31	31
RAD50	0.039	0.011	-10000	0	0	38	38
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.037	0.013	-10000	0	0	61	61
TRF2/BLM	0.043	0.044	-10000	0	-0.13	21	21
FRAP1	0.04	0.009	-10000	0	0	24	24
KU/TERT	-0.014	0.19	-10000	0	-0.5	27	27
SP1/HDAC2	0.042	0.051	-10000	0	-0.1	22	22
PINX1	0.033	0.017	-10000	0	0	121	121
Telomerase/EST1A	-0.027	0.17	-10000	0	-0.46	29	29
Smad3/Myc	0.015	0.038	-10000	0	-0.14	19	19
911 complex	0.071	0.037	-10000	0	-0.12	9	9
IFNG	0.034	0.035	0.11	2	-0.11	24	26
Telomerase/PinX1	-0.026	0.17	-10000	0	-0.46	31	31
Telomerase/AKT1/mTOR/p70S6K	-0.003	0.1	-10000	0	-0.28	41	41
SIN3B	0.037	0.014	-10000	0	0	67	67
YWHAE	0.038	0.012	-10000	0	0	50	50
Telomerase/EST1B	-0.027	0.17	-10000	0	-0.46	29	29
response to DNA damage stimulus	0.002	0.035	0.063	3	-0.1	50	53
MRN complex/TRF2/Rap1	0.066	0.08	-10000	0	-0.12	45	45
TRF2/WRN	0.038	0.04	-10000	0	-0.11	19	19
Telomerase/hnRNP C1/C2	-0.027	0.17	-10000	0	-0.46	29	29
E2F1	0.031	0.027	-10000	0	-0.033	70	70
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

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.038	0.012	-10000	0	0	50	50
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.04	0.008	-10000	0	0	22	22
TCEB1	0.038	0.012	-10000	0	0	49	49
HIF1A/p53	0	0.087	0.22	1	-0.27	35	36
HIF1A	-0.002	0.074	0.16	4	-0.26	29	33
COPS5	0.035	0.015	-10000	0	0	84	84
VHL/Elongin B/Elongin C/RBX1/CUL2	0.085	0.071	-10000	0	-0.12	27	27
FIH (dimer)	0.04	0.009	-10000	0	0	25	25
CDKN2A	0.028	0.019	-10000	0	0	176	176
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	0.013	0.086	0.22	1	-0.29	24	25
CUL2	0.039	0.011	-10000	0	0	38	38
OS9	0.039	0.01	-10000	0	0	37	37
RACK1/Elongin B/Elongin C	0.071	0.037	-10000	0	-0.12	10	10
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.006	0.074	0.15	4	-0.29	22	26
PHD1-3/OS9	0.052	0.081	-10000	0	-0.11	88	88
HIF1A/RACK1/Elongin B/Elongin C	0.047	0.091	-10000	0	-0.29	20	20
VHL	0.04	0.009	-10000	0	0	27	27
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	0.011	0.081	0.22	1	-0.28	24	25
EGLN3	0.028	0.02	-10000	0	0	185	185
EGLN2	0.04	0.009	-10000	0	0	27	27
EGLN1	0.039	0.01	-10000	0	0	35	35
TP53	0.027	0.02	-10000	0	0	200	200
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.023	0.13	-10000	0	-0.56	22	22
ARNT	0.041	0.006	-10000	0	0	13	13
ARD1A	0.04	0.009	-10000	0	0	30	30
RBX1	0.037	0.014	-10000	0	0	68	68
HIF1A/p19ARF	0.003	0.084	-10000	0	-0.28	29	29

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.036	0.027	0.097	1	-0.069	30	31
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	62	66
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.015	0.041	-10000	0	-0.13	40	40
NFKBIA	-0.035	0.067	0.24	4	-0.28	29	33
BIRC2	0.036	0.014	-10000	0	0	73	73
IKBKB	0.038	0.011	-10000	0	0	44	44
RIPK2	0.032	0.018	-10000	0	0	125	125
IKBKG	-0.006	0.11	-10000	0	-0.3	48	48
IKK complex/A20	0.032	0.12	-10000	0	-0.31	31	31
NEMO/A20/RIP2	0.032	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	-0.31	52	52
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	11	11
Exportin 1/RanGTP	0.047	0.036	-10000	0	-0.11	24	24
IKK complex/ELKS	0.005	0.11	-10000	0	-0.28	48	48
BCL10/MALT1/TRAF6	0.063	0.049	-10000	0	-0.13	20	20
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.032	0.028	-10000	0	-0.072	24	24
RELA	0.036	0.028	0.097	1	-0.068	33	34
MALT1	0.036	0.015	-10000	0	0	80	80
cIAP1/UbcH5C	0.039	0.053	-10000	0	-0.14	38	38
ATM	0.036	0.014	-10000	0	0	72	72
TNF/TNFR1A	0.047	0.038	-10000	0	-0.14	15	15
TRAF6	0.04	0.009	-10000	0	0	24	24
PRKCA	0.035	0.016	-10000	0	0	91	91
CHUK	0.038	0.012	-10000	0	0	52	52
UBE2D3	0.038	0.012	-10000	0	0	50	50
TNF	0.04	0.009	-10000	0	0	25	25
NF kappa B1 p50/RelA	0.057	0.081	-10000	0	-0.15	59	59
BCL10	0.041	0.006	-10000	0	0	12	12
proteasomal ubiquitin-dependent protein catabolic process	-0.035	0.066	0.24	4	-0.28	29	33
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.027	0.097	1	-0.069	30	31
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
IKK complex	0.018	0.13	-10000	0	-0.31	46	46
CYLD	0.038	0.012	-10000	0	0	51	51
IKK complex/PKC alpha	0.022	0.13	-10000	0	-0.3	47	47

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.06	-10000	0	-0.11	41	41
NGF (dimer)/p75(NTR)/BEX1	0.022	0.053	-10000	0	-0.11	61	61
NT-4/5 (dimer)/p75(NTR)	0.029	0.009	-10000	0	-0.13	1	1
IKBKB	0.038	0.011	-10000	0	0	44	44
AKT1	0.014	0.09	0.19	98	-0.18	6	104
IKBKG	0.042	0.003	-10000	0	0	2	2
BDNF	0.04	0.009	-10000	0	0	24	24
MGDIs/NGR/p75(NTR)/LINGO1	0.049	0.021	-10000	0	-0.11	3	3
FURIN	0.039	0.01	-10000	0	0	32	32
proBDNF (dimer)/p75(NTR)/Sortilin	0.066	0.048	-10000	0	-0.12	25	25
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.019	0.072	-10000	0	-0.13	79	79
proBDNF (dimer)	0.04	0.009	-10000	0	0	24	24
NTRK1	0.039	0.01	-10000	0	0	33	33
RTN4R	0.038	0.012	-10000	0	0	50	50
neuron apoptosis	-0.058	0.13	0.31	1	-0.36	46	47
IRAK1	0.04	0.008	-10000	0	0	19	19
SHC1	0.017	0.009	0.069	7	-0.11	1	8
ARHGDIA	0.038	0.013	-10000	0	0	56	56
RhoA/GTP	0.029	0.014	-10000	0	-0.13	4	4
Gamma Secretase	0.072	0.087	-10000	0	-0.12	68	68
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.056	0.057	-10000	0	-0.11	49	49
MAGEH1	0.038	0.011	-10000	0	0	44	44
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.053	0.054	-10000	0	-0.1	40	40
Mammalian IAPs/DIABLO	0.012	0.089	-10000	0	-0.13	127	127
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.04	0.009	-10000	0	0	25	25
APP	0.038	0.012	-10000	0	0	47	47
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	0.028	0.19	1	-0.11	8	9
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.017	0.04	0.2	3	-10000	0	3
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.063	-10000	0	-0.17	49	49
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.05	0.024	-10000	0	-0.11	8	8
NCSTN	0.04	0.008	-10000	0	0	21	21
mol:GTP	0.045	0.035	-10000	0	-0.11	23	23
PSENEN	0.035	0.015	-10000	0	0	88	88
mol:ceramide	-0.021	0.027	0.19	3	-10000	0	3
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.011	0.093	-10000	0	-0.32	22	22
p75(NTR)/beta APP	0.048	0.043	-10000	0	-0.14	24	24
BEX1	0.027	0.02	-10000	0	0	202	202
mol:GDP	-0.008	0.004	-10000	0	-0.1	1	1
NGF (dimer)	-0.004	0.074	-10000	0	-0.1	171	171
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.064	0.037	-10000	0	-0.1	8	8
PIK3R1	0.034	0.016	-10000	0	0	106	106
RAC1/GTP	0.044	0.016	-10000	0	-0.091	1	1
MYD88	0.041	0.007	-10000	0	0	15	15
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	22	22
RHOA	0.041	0.007	-10000	0	0	14	14
MAGE-G1/E2F1	0.053	0.024	-10000	0	-0.14	2	2
NT3 (dimer)	0.031	0.018	-10000	0	0	144	144
TP53	-0.023	0.047	0.21	9	-0.18	12	21
PRDM4	-0.022	0.027	0.19	3	-10000	0	3
BDNF (dimer)	0.019	0.091	-10000	0	-0.11	164	164
PIK3CA	0.03	0.019	-10000	0	0	150	150
SORT1	0.038	0.012	-10000	0	0	46	46
activation of caspase activity	0.065	0.057	-10000	0	-0.11	41	41
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.062	0.049	-10000	0	-0.11	33	33
RHOC	0.041	0.006	-10000	0	0	13	13
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.016	0.056	0.24	5	-0.21	10	15
DIABLO	0.037	0.013	-10000	0	0	64	64
SMPD2	-0.021	0.027	0.19	3	-10000	0	3
APH1B	0.035	0.015	-10000	0	0	86	86
APH1A	0.041	0.006	-10000	0	0	11	11
proNGF (dimer)/p75(NTR)/Sortilin	0.044	0.037	-10000	0	-0.11	26	26
PSEN1	0.039	0.01	-10000	0	0	34	34
APAF-1/Pro-Caspase 9	0.051	0.042	-10000	0	-0.15	20	20
NT3 (dimer)/p75(NTR)	0.041	0.038	-10000	0	-0.15	10	10
MAPK8	-0.019	0.064	0.24	7	-0.24	12	19
MAPK9	-0.02	0.061	0.23	6	-0.22	12	18
APAF1	0.039	0.01	-10000	0	0	33	33
NTF3	0.031	0.018	-10000	0	0	144	144
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.036	0.014	-10000	0	0	76	76
RAC1/GDP	0.029	0.01	-10000	0	-0.13	1	1
RhoA-B-C/GDP	0.073	0.051	-10000	0	-0.1	28	28
p75 CTF/Sortilin/TRAF6/NRIF	0.075	0.076	-10000	0	-0.13	57	57
RhoA-B-C/GTP	0.044	0.035	-10000	0	-0.11	23	23
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.098	0.065	-10000	0	-0.11	30	30
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.084	0.058	-10000	0	-0.12	31	31
PRKACB	0.038	0.012	-10000	0	0	49	49
proBDNF (dimer)/p75 ECD	0.046	0.048	-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	213	213
BIRC2	0.036	0.014	-10000	0	0	73	73
neuron projection morphogenesis	-0.019	0.05	0.16	3	-0.16	24	27
BAD	-0.024	0.067	0.24	5	-0.21	20	25
RIPK2	0.032	0.018	-10000	0	0	125	125
NGFR	0.04	0.009	-10000	0	0	26	26
CYCS	-0.026	0.033	0.19	2	-0.18	5	7
ADAM17	0.038	0.013	-10000	0	0	56	56
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.049	0.056	-10000	0	-0.11	43	43
BCL2L11	-0.024	0.067	0.26	4	-0.22	17	21
BDNF (dimer)/p75(NTR)	0.057	0.018	-10000	0	-0.11	1	1
PI3K	0.036	0.06	-10000	0	-0.12	48	48
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.061	0.046	-10000	0	-0.1	27	27
NDNL2	0.039	0.011	-10000	0	0	40	40
YWHAE	0.038	0.012	-10000	0	0	50	50
PRKCI	0.027	0.02	-10000	0	0	193	193
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	0.052	-10000	0	-0.11	38	38
TRAF6	0.04	0.009	-10000	0	0	24	24
RAC1	0.039	0.01	-10000	0	0	35	35
PRKCZ	0.042	0	-10000	0	-10000	0	0
PLG	0.038	0.012	-10000	0	0	50	50
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.013	0.044	0.16	6	-0.17	23	29
SQSTM1	0.038	0.012	-10000	0	0	48	48
NGFRAP1	0.041	0.007	-10000	0	0	15	15
CASP3	-0.026	0.071	0.26	4	-0.23	25	29
E2F1	0.039	0.011	-10000	0	0	41	41
CASP9	0.04	0.009	-10000	0	0	26	26
IKK complex	0.046	0.1	-10000	0	-0.25	22	22
NGF (dimer)/TRKA	0.029	0.007	-10000	0	-10000	0	0
MMP7	0.016	0.02	-10000	0	0	336	336
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.079	0.054	-10000	0	-0.1	33	33
MMP3	0.038	0.013	-10000	0	0	56	56
APAF-1/Caspase 9	-0.056	0.061	-10000	0	-0.2	50	50

×

Regulation of p38-alpha and p38-beta

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
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	98	98
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.037	0.013	-10000	0	0	59	59
RAC1-CDC42/GTP/PAK family	0.008	0.048	-10000	0	-0.15	32	32
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.037	0.013	-10000	0	0	59	59
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.04	0.008	-10000	0	0	19	19
FYN	0.034	0.016	-10000	0	0	102	102
MAP3K12	0.041	0.006	-10000	0	0	13	13
FGR	0.041	0.007	-10000	0	0	16	16
p38 alpha/TAB1	0.001	0.12	0.19	3	-0.25	57	60
PRKG1	0.04	0.009	-10000	0	0	30	30
DUSP8	0.04	0.009	-10000	0	0	27	27
PGK/cGMP/p38 alpha	-0.003	0.11	0.18	1	-0.25	59	60
apoptosis	0	0.11	0.18	3	-0.24	57	60
RAL/GTP	0.046	0.037	-10000	0	-0.11	25	25
LYN	0.036	0.015	-10000	0	0	83	83
DUSP1	0.027	0.02	-10000	0	0	202	202
PAK1	0.037	0.014	-10000	0	0	66	66
SRC	0.039	0.01	-10000	0	0	31	31
RAC1/OSM/MEKK3/MKK3	0.09	0.04	-10000	0	-0.11	1	1
TRAF6	0.04	0.009	-10000	0	0	24	24
RAC1	0.039	0.01	-10000	0	0	35	35
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	16	16
RAC1-CDC42/GTP	0.05	0.022	-10000	0	-0.14	3	3
MAPK11	-0.028	0.12	0.2	2	-0.29	66	68
BLK	0.033	0.017	-10000	0	0	115	115
HCK	0.036	0.015	-10000	0	0	79	79
MAP2K3	0.039	0.011	-10000	0	0	43	43
DUSP16	0.035	0.015	-10000	0	0	84	84
DUSP10	0.034	0.017	-10000	0	0	107	107
TRAF6/MEKK3	0.048	0.022	-10000	0	-0.098	8	8
MAP3K7IP1	0.038	0.012	-10000	0	0	51	51
MAPK14	-0.01	0.12	0.19	3	-0.27	59	62
positive regulation of innate immune response	-0.024	0.14	0.23	2	-0.33	60	62
LCK	0.04	0.009	-10000	0	0	28	28
p38alpha-beta/MKP7	-0.013	0.14	0.24	2	-0.32	57	59
p38alpha-beta/MKP5	-0.017	0.14	0.24	2	-0.31	62	64
PGK/cGMP	0.029	0.007	-10000	0	-10000	0	0
PAK2	0.04	0.009	-10000	0	0	24	24
p38alpha-beta/MKP1	-0.028	0.14	0.25	1	-0.33	63	64
CDC42	0.04	0.008	-10000	0	0	22	22
RALB	0.04	0.009	-10000	0	0	27	27
RALA	0.04	0.009	-10000	0	0	29	29
PAK3	0.037	0.013	-10000	0	0	62	62

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.013	0.01	0.015	29	-10000	0	29
RAS family/GTP	0.017	0.1	0.26	3	-0.21	28	31
NFATC4	-0.018	0.081	0.23	22	-0.18	4	26
ERBB2IP	0.036	0.015	-10000	0	-0.001	72	72
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.001	0.08	0.24	2	-0.16	54	56
JUN	0.008	0.086	0.22	3	-10000	0	3
HRAS	0.04	0.009	-10000	0	0	29	29
DOCK7	-0.024	0.083	0.2	22	-0.2	13	35
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.036	0.08	0.21	18	-0.12	71	89
AKT1	-0.005	0.012	0.021	29	-10000	0	29
BAD	-0.015	0.007	0.012	12	-10000	0	12
MAPK10	-0.008	0.07	0.18	28	-0.14	7	35
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0	0.086	0.26	2	-0.17	54	56
RAF1	0.008	0.11	0.26	28	-0.23	29	57
ErbB2/ErbB3/neuregulin 2	0.028	0.076	0.18	38	-0.12	78	116
STAT3	-0.021	0.24	-10000	0	-0.92	37	37
cell migration	-0.008	0.073	0.2	26	-0.17	12	38
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.03	0.23	0.4	4	-0.56	53	57
FOS	-0.034	0.22	0.36	7	-0.4	126	133
NRAS	0.039	0.01	-10000	0	0	31	31
mol:Ca2+	-0.001	0.08	0.24	2	-0.16	54	56
MAPK3	-0.011	0.19	0.37	3	-0.49	40	43
MAPK1	-0.023	0.2	0.37	4	-0.49	48	52
JAK2	-0.023	0.079	0.2	18	-0.21	10	28
NF2	0.005	0.071	-10000	0	-0.72	5	5
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.002	0.073	0.18	3	-0.17	64	67
NRG1	0.035	0.016	-10000	0	0	90	90
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
MAPK8	-0.019	0.11	0.21	10	-0.22	88	98
MAPK9	-0.011	0.071	0.19	26	-0.15	10	36
ERBB2	-0.024	0.04	0.26	9	-10000	0	9
ERBB3	0.033	0.018	-10000	0	0	124	124
SHC1	0.04	0.009	-10000	0	0	29	29
RAC1	0.039	0.01	-10000	0	0	35	35
apoptosis	0.005	0.027	0.18	1	-0.21	7	8
STAT3 (dimer)	-0.017	0.24	-10000	0	-0.9	37	37
RNF41	-0.017	0.016	0.047	11	-0.12	3	14
FRAP1	-0.014	0.007	0.012	12	-10000	0	12
RAC1-CDC42/GTP	-0.031	0.056	0.09	16	-0.14	41	57
ErbB2/ErbB2/HSP90 (dimer)	-0.024	0.015	0.018	3	-0.12	5	8
CHRNA1	0.005	0.15	0.35	6	-0.37	32	38
myelination	-0.01	0.097	0.25	34	-0.2	4	38
PPP3CB	-0.021	0.079	0.2	18	-0.18	7	25
KRAS	0.034	0.016	-10000	0	0	103	103
RAC1-CDC42/GDP	0.021	0.099	0.21	3	-0.17	67	70
NRG2	0.041	0.006	-10000	0	0	12	12
mol:GDP	-0.002	0.072	0.18	3	-0.17	64	67
SOS1	0.038	0.013	-10000	0	0	57	57
MAP2K2	-0.006	0.11	0.25	23	-0.22	43	66
SRC	0.039	0.01	-10000	0	0	31	31
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.022	0.085	0.21	20	-0.2	11	31
MAP2K1	-0.017	0.19	0.38	1	-0.52	30	31
heart morphogenesis	-0.001	0.08	0.24	2	-0.16	54	56
RAS family/GDP	0.026	0.1	0.26	3	-0.18	48	51
GRB2	0.041	0.007	-10000	0	0	14	14
PRKACA	0.009	0.078	-10000	0	-0.72	6	6
CHRNE	0.007	0.023	-10000	0	-10000	0	0
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	0.08	0.24	2	-0.16	54	56
CDC42	0.04	0.008	-10000	0	0	22	22

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.038	0.19	0.33	11	-0.98	21	32
VDR	0.037	0.013	-10000	0	0	58	58
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.024	0.09	-10000	0	-0.24	44	44
RXRs/LXRs/DNA/Oxysterols	0.017	0.12	-10000	0	-0.34	53	53
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0.001	0.016	0.057	1	-0.047	48	49
RARs/THRs/DNA/Src-1	-0.004	0.094	-10000	0	-0.18	110	110
RXRs/NUR77	0.079	0.072	0.3	1	-0.12	5	6
RXRs/PPAR	0.027	0.054	-10000	0	-0.16	12	12
NCOR2	0.04	0.009	-10000	0	0	26	26
VDR/VDR/Vit D3	0.022	0.032	-10000	0	-0.13	23	23
RARs/VDR/DNA/Vit D3	0.064	0.069	-10000	0	-0.11	59	59
RARA	0.039	0.01	-10000	0	0	34	34
NCOA1	0.04	0.009	-10000	0	0	28	28
VDR/VDR/DNA	0.037	0.013	-10000	0	0	58	58
RARs/RARs/DNA/9cRA	0.052	0.053	-10000	0	-0.097	50	50
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	-0.002	0.09	-10000	0	-0.17	107	107
THRA	0.039	0.011	-10000	0	0	39	39
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.022	0.032	-10000	0	-0.13	23	23
RXRs/PPAR/9cRA/PGJ2/DNA	0.07	0.078	0.31	12	-0.15	34	46
NR1H4	0.041	0.007	-10000	0	0	15	15
RXRs/LXRs/DNA	0.094	0.1	0.32	1	-0.2	30	31
NR1H2	0.034	0.032	-10000	0	-0.058	51	51
NR1H3	0.035	0.034	-10000	0	-0.065	52	52
RXRs/VDR/DNA/Vit D3	0.072	0.072	0.28	1	-0.13	10	11
NR4A1	0.034	0.016	-10000	0	0	99	99
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.023	0.041	0.14	3	-0.14	5	8
RXRG	0.032	0.031	0.099	1	-0.055	44	45
RXR alpha/CCPG	0.026	0.022	-10000	0	-0.11	1	1
RXRA	0.035	0.031	0.099	1	-0.056	50	51
RXRB	0.036	0.034	0.1	1	-0.063	53	54
THRB	0.034	0.017	-10000	0	0	107	107
PPARG	0.039	0.01	-10000	0	0	34	34
PPARD	0.04	0.008	-10000	0	0	23	23
TNF	0.009	0.12	-10000	0	-0.51	8	8
mol:Oxysterols	0	0.014	-10000	0	-0.04	58	58
cholesterol transport	0.017	0.12	-10000	0	-0.34	53	53
PPARA	0.034	0.016	-10000	0	0	98	98
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.036	0.015	-10000	0	0	78	78
RXRs/NUR77/BCL2	0.021	0.047	-10000	0	-0.14	22	22
SREBF1	0.007	0.12	-10000	0	-0.58	5	5
RXRs/RXRs/DNA/9cRA	0.07	0.077	0.3	12	-0.15	34	46
ABCA1	-0.036	0.26	-10000	0	-0.8	54	54
RARs/THRs	0.07	0.092	-10000	0	-0.12	82	82
RXRs/FXR	0.088	0.068	0.3	1	-0.11	29	30
BCL2	0.036	0.014	-10000	0	0	76	76

×

EGFR-dependent Endothelin 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
HRAS	0.04	0.009	-10000	0	0	29	29
EGFR	0.036	0.014	-10000	0	0	73	73
EGF/EGFR	0.044	0.059	-10000	0	-0.099	55	55
EGF/EGFR dimer/SHC/GRB2/SOS1	0.081	0.077	-10000	0	-0.11	48	48
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.035	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	52	52
EGF/EGFR dimer/SHC	0.057	0.055	-10000	0	-0.12	33	33
mol:GDP	0.073	0.072	-10000	0	-0.11	48	48
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.034	0.016	-10000	0	0	100	100
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
HRAS/GTP	0.049	0.06	-10000	0	-0.11	47	47
SHC1	0.04	0.009	-10000	0	0	29	29
HRAS/GDP	0.069	0.072	-10000	0	-0.12	42	42
FRAP1	-0.016	0.074	0.2	40	-0.18	4	44
EGF/EGFR dimer	0.04	0.051	-10000	0	-0.13	37	37
SOS1	0.038	0.013	-10000	0	0	57	57
GRB2	0.041	0.007	-10000	0	0	14	14
ETA receptor/Endothelin-1	0.037	0.047	-10000	0	-0.14	25	25

×

Regulation of Androgen receptor activity

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
HDAC1	-0.017	0.007	-10000	0	-10000	0	0
SMARCC1	-0.012	0.17	-10000	0	-1.1	13	13
REL	0.04	0.007	-10000	0	0	18	18
HDAC7	-0.045	0.093	0.18	15	-0.22	73	88
JUN	0.036	0.015	-10000	0	0	80	80
EP300	0.036	0.014	-10000	0	0	72	72
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.012	0.021	0.063	13	-0.05	1	14
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	-0.002	0.12	0.28	6	-0.22	85	91
MAP2K6	0.028	0.025	-10000	0	-0.034	49	49
BRM/BAF57	0.031	0.059	-10000	0	-0.13	53	53
MAP2K4	0.031	0.024	-10000	0	-0.034	47	47
SMARCA2	0.032	0.018	-10000	0	-10000	0	0
PDE9A	-0.086	0.32	-10000	0	-0.82	85	85
NCOA2	0.037	0.014	-10000	0	0	69	69
CEBPA	0.037	0.013	-10000	0	0	65	65
EHMT2	0.041	0.007	-10000	0	0	17	17
cell proliferation	-0.015	0.12	0.29	10	-0.3	34	44
NR0B1	0.039	0.011	-10000	0	0	38	38
EGR1	0.028	0.02	-10000	0	0	192	192
RXRs/9cRA	0.07	0.027	-10000	0	-0.1	3	3
AR/RACK1/Src	-0.014	0.092	0.21	28	-0.22	22	50
AR/GR	-0.011	0.093	0.21	2	-0.19	85	87
GNB2L1	0.042	0.005	-10000	0	0	7	7
PKN1	0.034	0.016	-10000	0	0	98	98
RCHY1	0.036	0.014	-10000	0	0	75	75
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.013	0.021	0.052	6	-0.059	1	7
T-DHT/AR/TIF2/CARM1	0.004	0.088	0.24	6	-0.21	25	31
SRC	-0.017	0.064	0.17	39	-0.15	7	46
NR3C1	0.038	0.011	-10000	0	0	44	44
KLK3	0.005	0.072	-10000	0	-10000	0	0
APPBP2	0.03	0.027	-10000	0	-0.034	67	67
TRIM24	0.039	0.012	-10000	0	0	44	44
T-DHT/AR/TIP60	-0.036	0.059	0.097	2	-0.16	60	62
TMPRSS2	0.013	0.12	-10000	0	-0.57	13	13
RXRG	0.036	0.015	-10000	0	0	84	84
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.04	0.01	-10000	0	0	31	31
RXRB	0.041	0.007	-10000	0	0	16	16
CARM1	0.037	0.014	-10000	0	0	70	70
NR2C2	0.041	0.007	-10000	0	0	16	16
KLK2	-0.001	0.073	0.26	2	-0.3	4	6
AR	-0.018	0.078	0.15	10	-0.19	69	79
SENP1	0.039	0.01	-10000	0	0	37	37
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	34	34
MYST2	0.04	0.009	-10000	0	0	25	25
HOXB13	0.04	0.01	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.017	0.094	0.21	28	-0.22	23	51
positive regulation of transcription	0.039	0.01	-10000	0	0	34	34
DNAJA1	0.03	0.026	-10000	0	-0.034	65	65
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.091	0.17	23	-0.25	52	75
NCOA1	0.041	0.034	0.12	3	-0.18	11	14
SPDEF	0.037	0.015	-10000	0	0	74	74
T-DHT/AR/TIF2	-0.011	0.096	0.2	10	-0.25	48	58
T-DHT/AR/Hsp90	-0.035	0.059	0.089	3	-0.16	62	65
GSK3B	0.04	0.009	-10000	0	0	29	29
NR2C1	0.039	0.011	-10000	0	0	40	40
mol:T-DHT	-0.023	0.052	0.19	14	-0.16	8	22
SIRT1	0.04	0.008	-10000	0	0	19	19
ZMIZ2	-0.001	0.001	-10000	0	-10000	0	0
POU2F1	0.033	0.057	0.12	3	-0.11	73	76
T-DHT/AR/DAX-1	-0.021	0.082	0.2	21	-0.21	25	46
CREBBP	0.038	0.012	-10000	0	0	49	49
SMARCE1	0.039	0.011	-10000	0	0	42	42

×

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	0.01	-10000	0	0	35	35
RAS family/GTP/Tiam1	0.012	0.06	-10000	0	-0.16	39	39
NT3 (dimer)/TRKC	0.04	0.036	-10000	0	-0.14	9	9
NT3 (dimer)/TRKB	0.055	0.046	-10000	0	-0.12	10	10
SHC/Grb2/SOS1/GAB1/PI3K	-0.001	0.08	-10000	0	-0.19	61	61
RAPGEF1	0.04	0.008	-10000	0	0	22	22
BDNF	0.04	0.009	-10000	0	0	24	24
PIK3CA	0.03	0.019	-10000	0	0	150	150
DYNLT1	0.035	0.015	-10000	0	0	84	84
NTRK1	0.039	0.01	-10000	0	0	33	33
NTRK2	0.039	0.011	-10000	0	0	39	39
NTRK3	0.038	0.012	-10000	0	0	50	50
NT-4/5 (dimer)/TRKB	0.05	0.018	-10000	0	-0.087	1	1
neuron apoptosis	-0.029	0.1	0.26	27	-0.23	2	29
SHC 2-3/Grb2	0.03	0.11	0.24	1	-0.27	29	30
SHC1	0.04	0.009	-10000	0	0	29	29
SHC2	0.003	0.12	0.21	2	-0.36	46	48
SHC3	0.026	0.082	0.22	1	-0.4	12	13
STAT3 (dimer)	0.003	0.11	-10000	0	-0.27	75	75
NT3 (dimer)/TRKA	0.054	0.047	-10000	0	-0.13	10	10
RIN/GDP	0.048	0.083	0.22	28	-0.19	20	48
GIPC1	0.035	0.015	-10000	0	0	89	89
KRAS	0.034	0.016	-10000	0	0	103	103
DNAJA3	0.009	0.051	0.15	10	-0.14	12	22
RIN/GTP	0.029	0.008	-10000	0	-10000	0	0
CCND1	-0.048	0.17	-10000	0	-0.49	73	73
MAGED1	0.04	0.009	-10000	0	0	25	25
PTPN11	0.04	0.009	-10000	0	0	29	29
RICS	0.037	0.014	-10000	0	0	69	69
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.065	0.05	-10000	0	-0.12	25	25
GRB2	0.041	0.007	-10000	0	0	14	14
NGF (dimer)/TRKA/MATK	0.048	0.02	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.046	0.039	-10000	0	-0.14	16	16
ELMO1	0.035	0.015	-10000	0	0	87	87
RhoG/GTP/ELMO1/DOCK1	0.034	0.047	-10000	0	-0.11	42	42
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.04	0.009	-10000	0	0	29	29
DOCK1	0.037	0.013	-10000	0	0	63	63
GAB2	0.031	0.018	-10000	0	0	142	142
RIT2	0.039	0.011	-10000	0	0	38	38
RIT1	0.038	0.011	-10000	0	0	44	44
FRS2	0.039	0.01	-10000	0	0	37	37
DNM1	0.039	0.01	-10000	0	0	36	36
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.011	-10000	0	0	45	45
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.026	0.061	0.17	8	-0.16	12	20
mol:GDP	0.044	0.1	0.26	28	-0.28	21	49
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.022	0.03	-10000	0	-0.13	19	19
RIT1/GDP	0.044	0.082	0.22	22	-0.19	23	45
TIAM1	0.037	0.014	-10000	0	0	70	70
PIK3R1	0.034	0.016	-10000	0	0	106	106
BDNF (dimer)/TRKB	0.07	0.033	-10000	0	-0.12	1	1
KIDINS220/CRKL/C3G	0.056	0.018	-10000	0	-10000	0	0
SHC/RasGAP	0.047	0.039	-10000	0	-0.13	17	17
FRS2 family/SHP2	0.067	0.05	-10000	0	-0.12	26	26
SHC/GRB2/SOS1/GAB1	0.079	0.061	-10000	0	-0.12	30	30
RIT1/GTP	0.025	0.026	-10000	0	-0.13	15	15
NT3 (dimer)	0.031	0.018	-10000	0	0	144	144
RAP1/GDP	0.033	0.071	0.17	18	-0.17	25	43
KIDINS220/CRKL	0.039	0.01	-10000	0	0	35	35
BDNF (dimer)	0.04	0.009	-10000	0	0	24	24
ubiquitin-dependent protein catabolic process	0.041	0.034	-10000	0	-0.11	16	16
Schwann cell development	-0.007	0.011	-10000	0	-0.044	10	10
EHD4	0.039	0.011	-10000	0	0	38	38
FRS2 family/GRB2/SOS1	0.082	0.06	-10000	0	-0.12	29	29
FRS2 family/SHP2/CRK family/C3G/GAB2	0.007	0.081	-10000	0	-0.22	34	34
RAP1B	0.038	0.013	-10000	0	0	57	57
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.067	0.053	0.18	26	-0.11	9	35
ABL1	0.039	0.011	-10000	0	0	41	41
SH2B family/GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
Rap1/GTP	0.009	0.11	-10000	0	-0.27	50	50
STAT3	0.003	0.11	-10000	0	-0.27	75	75
axon guidance	0.046	0.041	-10000	0	-0.11	9	9
MAPK3	-0.009	0.045	0.19	25	-10000	0	25
MAPK1	-0.008	0.045	0.19	25	-10000	0	25
CDC42/GDP	0.05	0.084	0.22	30	-0.19	20	50
NTF3	0.031	0.018	-10000	0	0	144	144
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.049	0.021	-10000	0	-0.11	2	2
PI3K	0.024	0.062	-10000	0	-0.15	47	47
FRS3	0.04	0.008	-10000	0	0	23	23
FAIM	0.038	0.012	-10000	0	0	48	48
GAB1	0.038	0.012	-10000	0	0	49	49
RASGRF1	0.009	0.052	0.15	10	-0.15	12	22
SOS1	0.038	0.013	-10000	0	0	57	57
MCF2L	0.004	0.06	0.18	38	-0.12	9	47
RGS19	0.036	0.015	-10000	0	0	80	80
CDC42	0.04	0.008	-10000	0	0	22	22
RAS family/GTP	0.036	0.12	0.29	4	-0.35	28	32
Rac1/GDP	0.048	0.084	0.22	30	-0.19	22	52
NGF (dimer)/TRKA/GRIT	0.042	0.036	-10000	0	-0.11	20	20
neuron projection morphogenesis	-0.049	0.24	-10000	0	-0.83	40	40
NGF (dimer)/TRKA/NEDD4-2	0.042	0.034	-10000	0	-0.11	16	16
MAP2K1	-0.011	0.073	0.2	46	-0.19	3	49
NGFR	0.04	0.009	-10000	0	0	26	26
NGF (dimer)/TRKA/GIPC/GAIP	0.014	0.04	-10000	0	-0.15	23	23
RAS family/GTP/PI3K	-0.004	0.071	-10000	0	-0.19	51	51
FRS2 family/SHP2/GRB2/SOS1	0.091	0.075	-10000	0	-0.13	39	39
NRAS	0.039	0.01	-10000	0	0	31	31
GRB2/SOS1	0.048	0.046	-10000	0	-0.14	26	26
PRKCI	0.027	0.02	-10000	0	0	193	193
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.039	0.01	-10000	0	0	35	35
PRKCZ	0.042	0	-10000	0	-10000	0	0
MAPKKK cascade	0.026	0.045	-10000	0	-0.45	2	2
RASA1	0.036	0.014	-10000	0	0	73	73
TRKA/c-Abl	0.051	0.034	-10000	0	-0.14	12	12
SQSTM1	0.038	0.012	-10000	0	0	48	48
BDNF (dimer)/TRKB/GIPC	0.07	0.059	-10000	0	-0.12	20	20
NGF (dimer)/TRKA/p62/Atypical PKCs	0.048	0.069	-10000	0	-0.11	54	54
MATK	0.037	0.013	-10000	0	0	58	58
NEDD4L	0.035	0.015	-10000	0	0	84	84
RAS family/GDP	-0.008	0.037	-10000	0	-0.14	23	23
NGF (dimer)/TRKA	0.015	0.051	0.16	6	-0.15	13	19
Rac1/GTP	-0.004	0.048	-10000	0	-0.15	13	13
FRS2 family/SHP2/CRK family	0.089	0.068	-10000	0	-0.12	24	24

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.06	0.1	0.3	18	-0.27	13	31
PDGFB-D/PDGFRB/SLAP	0.032	0.038	-10000	0	-0.14	10	10
PDGFB-D/PDGFRB/APS/CBL	0.047	0.024	-10000	0	-0.11	4	4
AKT1	0.021	0.1	0.25	44	-0.18	1	45
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.044	0.093	0.27	18	-0.3	12	30
PIK3CA	0.03	0.019	-10000	0	0	150	150
FGR	0.022	0.09	0.3	5	-0.39	12	17
mol:Ca2+	0.025	0.086	0.25	15	-0.35	11	26
MYC	0.007	0.28	0.41	9	-0.67	71	80
SHC1	0.04	0.009	-10000	0	0	29	29
HRAS/GDP	0.037	0.058	0.19	38	-0.11	17	55
LRP1/PDGFRB/PDGFB	0.055	0.056	-10000	0	-0.12	35	35
GRB10	0.04	0.008	-10000	0	0	23	23
PTPN11	0.04	0.009	-10000	0	0	29	29
GO:0007205	0.025	0.087	0.25	15	-0.35	11	26
PTEN	0.039	0.011	-10000	0	0	39	39
GRB2	0.041	0.007	-10000	0	0	14	14
GRB7	0.037	0.013	-10000	0	0	62	62
PDGFB-D/PDGFRB/SHP2	0.046	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	0.031	0.038	-10000	0	-0.14	10	10
HRAS	0.04	0.009	-10000	0	0	29	29
HIF1A	0.008	0.093	0.23	38	-0.2	6	44
GAB1	0.021	0.1	0.26	12	-0.28	20	32
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.024	0.11	0.24	45	-0.25	24	69
PDGFB-D/PDGFRB	0.058	0.051	-10000	0	-0.074	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.048	0.042	-10000	0	-0.14	21	21
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.053	0.12	0.31	16	-0.24	38	54
positive regulation of MAPKKK cascade	0.046	0.043	-10000	0	-0.14	22	22
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	0.025	0.087	0.25	15	-0.36	11	26
E5	0	0.002	-10000	0	-10000	0	0
CSK	0.04	0.01	-10000	0	-0.003	24	24
PDGFB-D/PDGFRB/GRB7	0.047	0.035	-10000	0	-0.14	10	10
SHB	0.041	0.007	-10000	0	0	16	16
BLK	-0.036	0.16	0.29	5	-0.37	93	98
PTPN2	0.039	0.015	-10000	0	-0.013	39	39
PDGFB-D/PDGFRB/SNX15	0.054	0.025	-10000	0	-0.14	3	3
BCAR1	0.036	0.014	-10000	0	0	74	74
VAV2	0.01	0.13	0.28	14	-0.31	48	62
CBL	0.04	0.008	-10000	0	0	23	23
PDGFB-D/PDGFRB/DEP1	0.047	0.041	-10000	0	-0.13	19	19
LCK	0.028	0.075	0.28	7	-0.39	5	12
PDGFRB	0.036	0.019	0.068	1	-0.007	81	82
ACP1	0.04	0.009	-10000	0	0	26	26
HCK	0.014	0.096	0.28	6	-0.44	15	21
ABL1	0.018	0.091	0.25	16	-0.23	24	40
PDGFB-D/PDGFRB/CBL	0.022	0.1	0.28	8	-0.31	21	29
PTPN1	0.037	0.017	-10000	0	-0.008	62	62
SNX15	0.041	0.005	-10000	0	0	7	7
STAT3	0.038	0.012	-10000	0	0	52	52
STAT1	0.034	0.017	-10000	0	0	108	108
cell proliferation	0.015	0.26	0.34	20	-0.6	71	91
SLA	0.026	0.02	-10000	0	0	205	205
actin cytoskeleton reorganization	0.007	0.093	0.22	64	-0.18	1	65
SRC	0.026	0.057	0.31	4	-10000	0	4
PI3K	-0.028	0.036	-10000	0	-0.12	29	29
PDGFB-D/PDGFRB/GRB7/SHC	0.064	0.042	-10000	0	-0.12	10	10
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.044	0.095	0.27	18	-0.31	12	30
LYN	0	0.12	0.31	4	-0.43	31	35
LRP1	0.036	0.014	-10000	0	0	73	73
SOS1	0.038	0.013	-10000	0	0	57	57
STAT5B	0.039	0.011	-10000	0	0	41	41
STAT5A	0.038	0.012	-10000	0	0	50	50
NCK1-2/p130 Cas	0.074	0.076	-10000	0	-0.12	21	21
SPHK1	0.042	0.008	-10000	0	0	16	16
EDG1	0.042	0.008	-10000	0	0	15	15
mol:DAG	0.025	0.087	0.25	15	-0.36	11	26
PLCG1	0.025	0.088	0.26	14	-0.36	11	25
NHERF/PDGFRB	0.062	0.046	-10000	0	-0.12	18	18
YES1	-0.001	0.13	0.27	3	-0.43	35	38
cell migration	0.059	0.048	-10000	0	-0.12	18	18
SHC/Grb2/SOS1	0.085	0.072	-10000	0	-0.13	23	23
SLC9A3R2	0.038	0.012	-10000	0	0	51	51
SLC9A3R1	0.038	0.012	-10000	0	0	47	47
NHERF1-2/PDGFRB/PTEN	0.078	0.058	-10000	0	-0.11	28	28
FYN	-0.015	0.14	0.27	4	-0.38	56	60
DOK1	0.005	0.067	0.19	51	-10000	0	51
HRAS/GTP	0.029	0.007	-10000	0	-10000	0	0
PDGFB	0.038	0.012	-10000	0	0	54	54
RAC1	-0.031	0.24	0.3	12	-0.53	75	87
PRKCD	0.003	0.066	0.2	45	-10000	0	45
FER	0.004	0.065	0.19	48	-10000	0	48
MAPKKK cascade	-0.003	0.081	0.2	46	-0.18	4	50
RASA1	0.003	0.062	0.19	41	-10000	0	41
NCK1	0.036	0.014	-10000	0	0	77	77
NCK2	0.041	0.006	-10000	0	0	10	10
p62DOK/Csk	0.054	0.055	0.2	52	-0.11	11	63
PDGFB-D/PDGFRB/SHB	0.053	0.026	-10000	0	-0.14	3	3
chemotaxis	0.018	0.089	0.25	16	-0.22	23	39
STAT1-3-5/STAT1-3-5	0.051	0.08	-10000	0	-0.12	57	57
Bovine Papilomavirus E5/PDGFRB	0.025	0.019	-10000	0	-0.034	25	25
PTPRJ	0.039	0.01	-10000	0	0	36	36

×

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	0.031	0.11	0.25	3	-0.29	25	28
CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
AKT1	0.039	0.011	-10000	0	0	38	38
AKT2	0.038	0.011	-10000	0	0	45	45
STXBP4	0.038	0.011	-10000	0	0	44	44
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.02	0.11	0.23	6	-0.29	28	34
YWHAZ	0.034	0.016	-10000	0	0	104	104
CALM1	0.04	0.009	-10000	0	0	30	30
YWHAQ	0.04	0.009	-10000	0	0	26	26
TBC1D4	-0.018	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.038	0.012	-10000	0	0	54	54
YWHAB	0.038	0.011	-10000	0	0	44	44
SNARE/Synip	0.045	0.029	-10000	0	-0.11	9	9
YWHAG	0.04	0.009	-10000	0	0	26	26
ASIP	0.038	0.012	-10000	0	0	51	51
PRKCI	0.027	0.02	-10000	0	0	193	193
AS160/CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
RHOQ	0.039	0.01	-10000	0	0	35	35
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	48	48
TC10/GTP/CIP4/Exocyst	0.046	0.029	-10000	0	-0.11	12	12
AS160/14-3-3	0.022	0.081	0.2	1	-0.26	21	22
VAMP2	0.037	0.013	-10000	0	0	62	62
SLC2A4	0.019	0.12	0.24	4	-0.32	29	33
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.023	0.026	-10000	0	-0.2	6	6
SFN	0.035	0.015	-10000	0	0	84	84
LNPEP	0.035	0.015	-10000	0	0	87	87
YWHAE	0.038	0.012	-10000	0	0	50	50

×

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	24	24
MKNK1	0.04	0.009	-10000	0	0	25	25
mol:PIP3	-0.014	0.038	0.2	1	-0.16	14	15
FRAP1	0.028	0.1	-10000	0	-0.42	20	20
AKT1	0.016	0.081	0.17	95	-0.18	10	105
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	0.09	0.24	28	-0.16	12	40
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.052	-10000	0	-0.19	25	25
TSC2	0.039	0.01	-10000	0	0	33	33
RHEB/GDP	0.028	0.069	0.16	5	-0.16	15	20
TSC1	0.04	0.009	-10000	0	0	27	27
Insulin Receptor/IRS1	0.033	0.033	-10000	0	-0.23	7	7
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.013	0.071	-10000	0	-0.22	24	24
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	-0.32	25	42
MAP3K5	-0.009	0.067	0.2	5	-0.22	47	52
PIK3R1	0.034	0.017	-10000	0	0	106	106
apoptosis	-0.01	0.067	0.2	5	-0.22	48	53
mol:LY294002	0	0	0.001	3	-0.001	7	10
EIF4B	0.024	0.1	0.25	16	-0.3	23	39
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.036	0.098	0.23	15	-0.28	24	39
eIF4E/eIF4G1/eIF4A1	0.012	0.062	-10000	0	-0.26	19	19
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.028	0.053	-10000	0	-0.16	16	16
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.075	0.2	20	-0.17	26	46
FKBP1A	0.039	0.011	-10000	0	0	39	39
RHEB/GTP	0.05	0.085	0.23	18	-0.16	15	33
mol:Amino Acids	0	0	0.001	3	-0.001	7	10
FKBP12/Rapamycin	0.029	0.013	-10000	0	-0.13	2	2
PDPK1	0.005	0.074	0.16	87	-0.17	11	98
EIF4E	0.038	0.011	-10000	0	0	44	44
ASK1/PP5C	0.011	0.2	-10000	0	-0.56	53	53
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.001	0.12	-10000	0	-0.42	22	22
TSC1/TSC2	0.056	0.096	0.26	27	-0.17	11	38
tumor necrosis factor receptor activity	0	0	0.001	7	-0.001	3	10
RPS6	0.038	0.011	-10000	0	0	44	44
PPP5C	0.04	0.009	-10000	0	0	27	27
EIF4G1	0.032	0.017	-10000	0	0	124	124
IRS1	0.01	0.03	-10000	0	-0.24	7	7
INS	0.04	0.009	-10000	0	0	30	30
PTEN	0.038	0.011	-10000	0	0	39	39
PDK2	0.005	0.073	0.16	84	-0.18	10	94
EIF4EBP1	-0.049	0.3	-10000	0	-1.1	43	43
PIK3CA	0.031	0.019	-10000	0	0	150	150
PPP2R5D	0.029	0.1	0.28	3	-0.38	20	23
peptide biosynthetic process	-0.014	0.031	0.19	10	-10000	0	10
RHEB	0.037	0.013	-10000	0	0	62	62
EIF4A1	0.039	0.01	-10000	0	0	35	35
mol:Rapamycin	0	0.001	0.004	46	-0.002	3	49
EEF2	-0.014	0.031	0.19	10	-10000	0	10
eIF4E/4E-BP1	-0.029	0.28	-10000	0	-0.99	43	43

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.017	0.055	-10000	0	-0.15	37	37
TRAF2/ASK1	0.044	0.035	-10000	0	-0.11	20	20
ATM	0.036	0.014	-10000	0	0	72	72
MAP2K3	-0.043	0.16	-10000	0	-0.32	103	103
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.044	0.14	0.21	2	-0.34	70	72
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	58	58
TXN	0.009	0.003	-10000	0	-10000	0	0
CALM1	0.04	0.009	-10000	0	0	30	30
GADD45A	0.036	0.014	-10000	0	0	71	71
GADD45B	0.034	0.016	-10000	0	0	100	100
MAP3K1	0.036	0.015	-10000	0	0	78	78
MAP3K6	0.04	0.008	-10000	0	0	21	21
MAP3K7	0.038	0.012	-10000	0	0	47	47
MAP3K4	0.038	0.012	-10000	0	0	50	50
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.048	0.041	-10000	0	-0.14	20	20
TAK1/TAB family	0.015	0.066	0.19	5	-0.27	19	24
RAC1/OSM/MEKK3	0.072	0.026	-10000	0	-0.1	1	1
TRAF2	0.04	0.009	-10000	0	0	25	25
RAC1/OSM/MEKK3/MKK3	-0.011	0.14	-10000	0	-0.27	95	95
TRAF6	0.008	0.043	-10000	0	-0.2	23	23
RAC1	0.039	0.01	-10000	0	0	35	35
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.04	0.007	-10000	0	0	18	18
CCM2	0.041	0.007	-10000	0	0	16	16
CaM/Ca2+/CAMKIIB	0.051	0.019	-10000	0	-0.11	3	3
MAPK11	0.032	0.018	-10000	0	0	132	132
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.061	0.044	-10000	0	-0.1	22	22
OSM/MEKK3	0.058	0.015	-10000	0	-10000	0	0
TAOK1	0.004	0.053	-10000	0	-0.2	35	35
TAOK2	0.005	0.052	-10000	0	-0.2	34	34
TAOK3	0.001	0.057	-10000	0	-0.2	42	42
MAP3K7IP1	0.038	0.012	-10000	0	0	51	51
MAPK14	0.04	0.009	-10000	0	0	28	28
MAP3K7IP2	0.037	0.013	-10000	0	0	63	63
MAP3K5	0.037	0.014	-10000	0	0	70	70
MAP3K10	0.039	0.011	-10000	0	0	39	39
MAP3K3	0.04	0.008	-10000	0	0	19	19
TRX/ASK1	0.022	0.047	-10000	0	-0.15	33	33
GADD45/MTK1/MTK1	0.054	0.068	-10000	0	-0.11	55	55

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.019	0.015	0.057	14	-10000	0	14
SNTA1	0.039	0.01	-10000	0	0	35	35
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.018	0.016	0.057	14	-10000	0	14
MAPK12	-0.009	0.041	0.21	5	-0.16	16	21
CCND1	-0.039	0.13	-10000	0	-0.37	72	72
p38 gamma/SNTA1	0.024	0.071	0.22	11	-0.17	29	40
MAP2K3	0.039	0.011	-10000	0	0	43	43
PKN1	0.034	0.016	-10000	0	0	98	98
G2/M transition checkpoint	-0.009	0.041	0.21	5	-0.16	16	21
MAP2K6	0.003	0.045	0.24	5	-0.17	21	26
MAPT	0.002	0.054	0.15	20	-0.19	15	35
MAPK13	-0.017	0.008	0	96	-10000	0	96
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.003	0.05	-10000	0	-0.2	31	31

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.038	0.011	-10000	0	0	44	44
VLDLR	0.032	0.018	-10000	0	0	129	129
LRPAP1	0.036	0.015	-10000	0	0	79	79
NUDC	0.04	0.009	-10000	0	0	25	25
RELN/LRP8	0.049	0.056	-10000	0	-0.12	30	30
CaM/Ca2+	0.028	0.016	-10000	0	-0.13	5	5
KATNA1	0.037	0.013	-10000	0	0	64	64
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.003	0.068	0.21	32	-0.19	1	33
IQGAP1/CaM	0.041	0.055	-10000	0	-0.14	43	43
DAB1	0.04	0.009	-10000	0	0	25	25
IQGAP1	0.037	0.014	-10000	0	0	67	67
PLA2G7	0.03	0.019	-10000	0	0	152	152
CALM1	0.04	0.009	-10000	0	0	30	30
DYNLT1	0.035	0.015	-10000	0	0	84	84
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.041	0.053	-10000	0	-0.14	37	37
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	27	27
LIS1/Poliovirus Protein 3A	-0.016	0.013	-10000	0	-0.12	6	6
CDK5R2	0.041	0.006	-10000	0	0	10	10
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	0.012	-10000	0	0	50	50
NDEL1/14-3-3 E	0.034	0.087	0.3	27	-0.17	7	34
MAP1B	-0.002	0.049	0.18	3	-0.18	33	36
RAC1	0.01	0.041	-10000	0	-0.59	1	1
p35/CDK5	-0.01	0.068	0.21	22	-0.18	1	23
RELN	0.034	0.016	-10000	0	0	104	104
PAFAH/LIS1	0.025	0.028	-10000	0	-0.15	6	6
LIS1/CLIP170	-0.016	0.013	-10000	0	-0.12	6	6
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.024	0.077	0.2	17	-0.18	12	29
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.004	0.099	-10000	0	-0.23	63	63
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.006	0.084	0.23	49	-0.16	4	53
LIS1/IQGAP1	0.031	0.027	-10000	0	-0.15	6	6
RHOA	0.011	0.045	0.12	17	-0.4	3	20
PAFAH1B1	-0.018	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.035	0.015	-10000	0	0	89	89
PAFAH1B2	0.04	0.009	-10000	0	0	29	29
MAP1B/LIS1/Dynein heavy chain	0.011	0.061	-10000	0	-0.15	38	38
NDEL1/Katanin 60/Dynein heavy chain	0.04	0.091	0.29	26	-0.18	8	34
LRP8	0.039	0.011	-10000	0	0	39	39
NDEL1/Katanin 60	0.031	0.081	0.25	36	-0.17	8	44
P39/CDK5	-0.009	0.072	0.2	32	-0.18	1	33
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.034	0.025	-10000	0	-0.15	6	6
CDK5	-0.011	0.053	0.19	18	-0.18	1	19
PPP2R5D	0.04	0.009	-10000	0	0	27	27
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.013	0.011	-10000	0	-0.1	6	6
CSNK2A1	0.039	0.011	-10000	0	0	40	40
RELN/VLDLR/DAB1/LIS1	0.055	0.064	0.2	15	-0.11	36	51
RELN/VLDLR	0.052	0.074	-10000	0	-0.11	59	59
CDC42	0.01	0.047	0.12	17	-0.13	29	46

×

Aurora A signaling

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
Aurora A/GADD45A	0.042	0.041	0.17	2	-0.16	9	11
BIRC5	0.037	0.013	-10000	0	0	58	58
NFKBIA	-0.004	0.028	0.25	1	-0.18	6	7
CPEB1	0.039	0.01	-10000	0	0	37	37
AKT1	-0.002	0.043	0.26	10	-0.18	7	17
NDEL1	0.039	0.01	-10000	0	0	33	33
Aurora A/BRCA1	0.027	0.049	0.15	2	-0.1	50	52
NDEL1/TACC3	0.045	0.052	0.17	1	-0.11	32	33
GADD45A	0.036	0.014	-10000	0	0	71	71
GSK3B	0.038	0.012	0.091	14	0	29	43
PAK1/Aurora A	0.043	0.04	0.17	2	-0.17	8	10
MDM2	0.039	0.01	-10000	0	0	35	35
JUB	0.037	0.013	-10000	0	0	58	58
TPX2	-0.015	0.009	-10000	0	-10000	0	0
TP53	-0.043	0.12	0.16	1	-0.24	133	134
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	30	30
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.048	0.055	0.18	1	-0.12	32	33
G2/M transition of mitotic cell cycle	0.027	0.049	0.15	2	-0.1	50	52
AURKA	0.01	0.03	0.13	12	-0.2	7	19
AURKB	0.001	0.061	-10000	0	-0.2	41	41
CDC25B	0.005	0.047	-10000	0	-0.22	19	19
G2/M transition checkpoint	0.034	0.044	0.15	2	-0.11	30	32
mRNA polyadenylation	0.039	0.035	0.15	2	-0.14	9	11
Aurora A/CPEB	0.039	0.036	0.15	2	-0.14	9	11
Aurora A/TACC1/TRAP/chTOG	0.056	0.075	0.21	2	-0.18	14	16
BRCA1	0.034	0.016	-10000	0	0	99	99
centrosome duplication	0.043	0.04	0.17	2	-0.17	8	10
regulation of centrosome cycle	0.044	0.051	0.17	1	-0.11	32	33
spindle assembly	0.054	0.073	0.21	2	-0.17	14	16
TDRD7	0.035	0.015	-10000	0	0	87	87
Aurora A/RasGAP/Survivin	0.045	0.072	0.2	4	-0.13	18	22
CENPA	0.009	0.052	-10000	0	-0.32	11	11
Aurora A/PP2A	0.046	0.038	0.17	2	-0.16	8	10
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.013	0.058	0.17	4	-0.24	10	14
negative regulation of DNA binding	-0.043	0.11	0.16	1	-0.24	133	134
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.057	0.017	-10000	0	-10000	0	0
RASA1	0.036	0.014	-10000	0	0	73	73
Ajuba/Aurora A	0.034	0.044	0.15	2	-0.11	30	32
mitotic prometaphase	0.003	0.024	0.074	56	-10000	0	56
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.03	0.13	12	-0.2	7	19
TACC1	0.035	0.016	-10000	0	0	91	91
TACC3	0.033	0.017	-10000	0	0	112	112
Aurora A/Antizyme1	0.029	0.044	0.15	1	-0.1	34	35
Aurora A/RasGAP	0.042	0.042	0.17	2	-0.17	9	11
OAZ1	0.033	0.017	-10000	0	0	110	110
RAN	0.041	0.006	-10000	0	0	11	11
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.034	0.017	0.091	12	0	87	99
GIT1	0.04	0.008	-10000	0	0	23	23
GIT1/beta-PIX/PAK1	0.066	0.043	-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	27	27
Aurora A/TPX2	0.018	0.036	0.15	1	-0.21	8	9
PAK1	0.037	0.014	-10000	0	0	66	66
CKAP5	0.038	0.011	-10000	0	0	45	45

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.026	0.2	-10000	0	-0.8	33	33
regulation of axonogenesis	-0.002	0.051	0.19	28	-10000	0	28
myoblast fusion	-0.012	0.1	0.35	36	-0.19	1	37
mol:GTP	0.017	0.066	-10000	0	-0.2	44	44
regulation of calcium-dependent cell-cell adhesion	-0.034	0.088	0.2	41	-10000	0	41
ARF1/GTP	0.038	0.059	-10000	0	-0.16	40	40
mol:GM1	0.003	0.047	-10000	0	-0.15	44	44
mol:Choline	0.001	0.039	0.092	1	-0.15	27	28
lamellipodium assembly	-0.013	0.12	-10000	0	-0.4	44	44
MAPK3	0.011	0.084	-10000	0	-0.28	39	39
ARF6/GTP/NME1/Tiam1	0.035	0.089	-10000	0	-0.2	41	41
ARF1	0.038	0.012	-10000	0	0	51	51
ARF6/GDP	0.012	0.1	0.19	1	-0.35	36	37
ARF1/GDP	0.015	0.1	-10000	0	-0.3	44	44
ARF6	0.043	0.045	-10000	0	-0.13	33	33
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	0.013	0.077	-10000	0	-0.28	33	33
actin filament bundle formation	-0.026	0.11	0.31	46	-10000	0	46
KALRN	0.004	0.074	-10000	0	-0.26	36	36
RAB11FIP3/RAB11A	0.058	0.023	-10000	0	-0.14	6	6
RhoA/GDP	0.027	0.11	-10000	0	-0.31	46	46
NME1	0.031	0.024	-10000	0	-0.047	30	30
Rac1/GDP	0.026	0.11	-10000	0	-0.31	45	45
substrate adhesion-dependent cell spreading	0.017	0.066	-10000	0	-0.2	44	44
cortical actin cytoskeleton organization	-0.013	0.12	-10000	0	-0.41	44	44
RAC1	0.039	0.01	-10000	0	0	35	35
liver development	0.017	0.066	-10000	0	-0.2	44	44
ARF6/GTP	0.017	0.066	-10000	0	-0.2	44	44
RhoA/GTP	0.041	0.063	-10000	0	-0.16	44	44
mol:GDP	-0.003	0.096	-10000	0	-0.34	37	37
ARF6/GTP/RAB11FIP3/RAB11A	0.061	0.066	-10000	0	-0.14	48	48
RHOA	0.041	0.007	-10000	0	0	14	14
PLD1	0.009	0.048	-10000	0	-0.17	31	31
RAB11FIP3	0.042	0.003	-10000	0	0	3	3
tube morphogenesis	-0.013	0.12	-10000	0	-0.4	44	44
ruffle organization	0.002	0.051	-10000	0	-0.19	28	28
regulation of epithelial cell migration	0.017	0.066	-10000	0	-0.2	44	44
PLD2	0.016	0.048	-10000	0	-0.15	40	40
PIP5K1A	0.002	0.051	-10000	0	-0.19	28	28
mol:Phosphatidic acid	0.001	0.039	0.092	1	-0.15	27	28
Rac1/GTP	-0.013	0.12	-10000	0	-0.41	44	44

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.028	0.093	-9999	-0.38	12	12
Syndecan-3/Neurocan	0.002	0.064	-9999	-0.42	12	12
POMC	0.04	0.007	-9999	0	18	18
EGFR	0.036	0.014	-9999	0	73	73
Syndecan-3/EGFR	0.03	0.072	-9999	-0.42	12	12
AGRP	0.036	0.014	-9999	0	74	74
NCSTN	0.04	0.008	-9999	0	21	21
PSENEN	0.035	0.015	-9999	0	88	88
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.035	0.015	-9999	0	86	86
APH1A	0.041	0.006	-9999	0	11	11
NCAN	0	0	-9999	-10000	0	0
long-term memory	0.038	0.079	-9999	-0.39	12	12
Syndecan-3/IL8	0.023	0.072	-9999	-0.43	12	12
PSEN1	0.039	0.01	-9999	0	34	34
Src/Cortactin	0.053	0.031	-9999	-0.14	10	10
FYN	0.034	0.016	-9999	0	102	102
limb bud formation	0.003	0.067	-9999	-0.43	12	12
MC4R	0	0	-9999	-10000	0	0
SRC	0.039	0.01	-9999	0	31	31
PTN	0.023	0.021	-9999	0	244	244
FGFR/FGF/Syndecan-3	0.003	0.067	-9999	-0.44	12	12
neuron projection morphogenesis	-0.013	0.069	-9999	-0.37	12	12
Syndecan-3/AgRP	0.03	0.071	-9999	-0.42	12	12
Syndecan-3/AgRP/MC4R	0.028	0.069	-9999	-0.41	12	12
Fyn/Cortactin	0.037	0.055	-9999	-0.14	43	43
SDC3	0.003	0.068	-9999	-0.44	12	12
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.023	0.071	-9999	-0.42	12	12
IL8	0.031	0.018	-9999	0	137	137
Syndecan-3/Fyn/Cortactin	0.04	0.08	-9999	-0.4	12	12
Syndecan-3/CASK	0.002	0.064	-9999	-0.42	12	12
alpha-MSH/MC4R	0.03	0.005	-9999	-10000	0	0
Gamma Secretase	0.072	0.087	-9999	-0.12	68	68

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.022	0.13	0.24	4	-0.39	38	42
BAG4	0.037	0.013	-10000	0	0	63	63
BAD	-0.008	0.047	0.17	5	-0.14	28	33
NFKBIA	0.037	0.014	-10000	0	0	66	66
BIRC3	0.026	0.02	-10000	0	0	213	213
BAX	-0.006	0.048	0.15	9	-0.14	27	36
EnzymeConsortium:3.1.4.12	-0.003	0.032	0.074	3	-0.085	36	39
IKBKB	-0.021	0.13	0.24	6	-0.37	36	42
MAP2K2	-0.01	0.039	0.15	3	-0.15	8	11
MAP2K1	-0.013	0.045	0.17	8	-0.15	9	17
SMPD1	-0.003	0.037	0.097	1	-0.11	34	35
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.013	0.14	0.24	8	-0.37	40	48
MAP2K4	-0.009	0.041	-10000	0	-0.14	21	21
protein ubiquitination	-0.027	0.13	0.24	2	-0.38	36	38
EnzymeConsortium:2.7.1.37	-0.013	0.044	0.15	5	-0.16	7	12
response to UV	0	0	0.002	7	-0.002	4	11
RAF1	-0.01	0.043	0.14	6	-0.14	17	23
CRADD	0.041	0.006	-10000	0	0	12	12
mol:ceramide	-0.004	0.046	0.12	1	-0.13	36	37
I-kappa-B-alpha/RELA/p50/ubiquitin	0.042	0.043	-10000	0	-0.11	36	36
MADD	0.041	0.006	-10000	0	0	12	12
MAP3K1	-0.008	0.044	0.12	1	-0.13	31	32
TRADD	0.036	0.014	-10000	0	0	76	76
RELA/p50	0.041	0.006	-10000	0	0	10	10
MAPK3	-0.008	0.043	0.16	4	-0.16	6	10
MAPK1	-0.012	0.052	0.16	5	-0.17	21	26
p50/RELA/I-kappa-B-alpha	0.045	0.051	-10000	0	-0.14	36	36
FADD	-0.017	0.13	0.24	9	-0.38	37	46
KSR1	-0.007	0.042	0.12	1	-0.13	26	27
MAPK8	-0.016	0.043	0.18	2	-0.14	13	15
TRAF2	0.04	0.009	-10000	0	0	25	25
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.03	0.13	0.24	2	-0.36	42	44
TNF R/SODD	0.044	0.038	-10000	0	-0.13	14	14
TNF	0.04	0.009	-10000	0	0	25	25
CYCS	-0.006	0.049	0.12	8	-0.14	22	30
IKBKG	-0.029	0.13	0.24	2	-0.38	37	39
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.017	0.14	-10000	0	-0.41	35	35
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	9	-0.14	21	30
TNF/TNF R/SODD	0.059	0.046	-10000	0	-0.12	15	15
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.018	0.13	-10000	0	-0.65	19	19
NSMAF	-0.013	0.14	0.24	16	-0.42	32	48
response to hydrogen peroxide	0	0	0.002	7	-0.002	4	11
BCL2	0.036	0.014	-10000	0	0	76	76

×

Class IB PI3K non-lipid kinase events

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
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 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
SMAD4	0.038	0.012	-10000	0	0	49	49
SMAD2	0.009	0.051	0.2	4	-0.2	6	10
SMAD3	0.013	0.054	0.22	2	-0.3	4	6
SMAD3/SMAD4	-0.016	0.16	-10000	0	-0.4	77	77
SMAD4/Ubc9/PIASy	0.066	0.042	-10000	0	-0.13	10	10
SMAD2/SMAD2/SMAD4	0.047	0.085	0.27	1	-0.18	10	11
PPM1A	0.041	0.007	-10000	0	0	16	16
CALM1	0.04	0.009	-10000	0	0	30	30
SMAD2/SMAD4	0.028	0.05	0.22	2	-0.18	6	8
MAP3K1	0.036	0.015	-10000	0	0	78	78
TRAP-1/SMAD4	0.048	0.043	-10000	0	-0.14	23	23
MAPK3	0.041	0.007	-10000	0	0	17	17
MAPK1	0.039	0.011	-10000	0	0	43	43
NUP214	0.039	0.01	-10000	0	0	32	32
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	12	12
KPNB1	0.04	0.009	-10000	0	0	29	29
TGFBRAP1	0.04	0.008	-10000	0	0	22	22
UBE2I	0.04	0.009	-10000	0	0	26	26
NUP153	0.037	0.014	-10000	0	0	69	69
KPNA2	0.035	0.015	-10000	0	0	84	84
PIAS4	0.038	0.013	-10000	0	0	56	56

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.037	0.042	-10000	0	-0.11	32	32
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	0.042	-10000	0	-0.11	32	32
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.037	0.042	-10000	0	-0.11	32	32
EPHA5	0.04	0.009	-10000	0	0	26	26

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.038	0.012	-10000	0	0	54	54
HDAC2	0.038	0.012	-10000	0	0	48	48
GNB1/GNG2	0.071	0.042	-10000	0	-0.12	18	18
forebrain development	0.016	0.11	-10000	0	-0.37	30	30
GNAO1	0.034	0.016	-10000	0	0	101	101
SMO/beta Arrestin2	0.055	0.025	-10000	0	-0.14	4	4
SMO	0.04	0.01	-10000	0	-0.001	32	32
ARRB2	0.039	0.011	-10000	0	0	37	37
GLI3/SPOP	0.023	0.13	0.25	4	-0.34	32	36
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.04	0.009	-10000	0	0	29	29
GNAI2	0.041	0.006	-10000	0	0	13	13
SIN3/HDAC complex	0.074	0.055	-10000	0	-0.12	11	11
GNAI1	0.035	0.016	-10000	0	0	94	94
XPO1	0.039	0.012	-10000	0	-0.002	42	42
GLI1/Su(fu)	0.024	0.11	-10000	0	-0.4	23	23
SAP30	0.038	0.013	-10000	0	0	55	55
mol:GDP	0.04	0.01	-10000	0	-0.001	32	32
MIM/GLI2A	0.031	0.026	-10000	0	-0.12	2	2
IFT88	0.037	0.014	-10000	0	0	67	67
GNAI3	0.038	0.012	-10000	0	0	46	46
GLI2	0.017	0.073	0.2	6	-0.24	15	21
GLI3	0.006	0.12	0.23	7	-0.36	31	38
CSNK1D	0.04	0.009	-10000	0	0	30	30
CSNK1E	0.038	0.012	-10000	0	0	54	54
SAP18	0.039	0.01	-10000	0	0	31	31
embryonic digit morphogenesis	0.037	0.014	-10000	0	0	67	67
GNG2	0.039	0.01	-10000	0	0	34	34
Gi family/GTP	0.002	0.076	-10000	0	-0.25	28	28
SIN3B	0.037	0.014	-10000	0	0	67	67
SIN3A	0.039	0.01	-10000	0	0	31	31
GLI3/Su(fu)	0.019	0.12	0.24	5	-0.31	38	43
GLI2/Su(fu)	0.026	0.081	0.19	6	-0.24	22	28
FOXA2	0.023	0.098	-10000	0	-0.55	13	13
neural tube patterning	0.016	0.11	-10000	0	-0.37	30	30
SPOP	0.04	0.009	-10000	0	0	26	26
Su(fu)/PIAS1	0.041	0.059	0.21	1	-0.18	27	28
GNB1	0.041	0.005	-10000	0	0	7	7
CSNK1G2	0.037	0.014	-10000	0	0	68	68
CSNK1G3	0.039	0.01	-10000	0	0	37	37
MTSS1	0.031	0.026	-10000	0	-0.12	2	2
embryonic limb morphogenesis	0.016	0.11	-10000	0	-0.37	30	30
SUFU	0.023	0.039	-10000	0	-0.24	10	10
LGALS3	0.037	0.014	-10000	0	0	68	68
catabolic process	0.029	0.13	0.3	1	-0.34	30	31
GLI3A/CBP	0.047	0.015	-10000	0	-10000	0	0
KIF3A	0.038	0.012	-10000	0	0	48	48
GLI1	0.015	0.11	-10000	0	-0.38	30	30
RAB23	0.041	0.007	-10000	0	0	16	16
CSNK1A1	0.04	0.009	-10000	0	0	24	24
IFT172	0.039	0.01	-10000	0	0	32	32
RBBP7	0.04	0.009	-10000	0	0	25	25
Su(fu)/Galectin3	0.038	0.058	0.21	1	-0.18	25	26
GNAZ	0.039	0.011	-10000	0	0	38	38
RBBP4	0.038	0.011	-10000	0	0	45	45
CSNK1G1	0.04	0.008	-10000	0	0	21	21
PIAS1	0.04	0.009	-10000	0	0	28	28
PRKACA	0.035	0.015	-10000	0	0	87	87
GLI2/SPOP	0.035	0.08	0.21	1	-0.24	16	17
STK36	0.04	0.011	-10000	0	-0.003	32	32
Gi family/GNB1/GNG2/GDP	0	0.085	-10000	0	-0.26	30	30
PTCH1	0.016	0.099	-10000	0	-0.34	30	30
MIM/GLI1	0.027	0.098	-10000	0	-0.35	20	20
CREBBP	0.047	0.015	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.004	0.11	0.18	7	-0.34	31	38

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.04	0.25	0.48	1	-0.58	53	54
PCK1	-0.1	0.41	-10000	0	-1.1	76	76
HNF4A	-0.075	0.35	0.57	3	-0.78	85	88
KCNJ11	-0.009	0.24	0.53	1	-0.56	28	29
AKT1	0.003	0.17	-10000	0	-0.34	28	28
response to starvation	-0.015	0.044	-10000	0	-0.12	76	76
DLK1	0	0.24	0.64	3	-0.57	27	30
NKX2-1	-0.007	0.15	0.34	3	-0.32	31	34
ACADM	-0.055	0.27	0.54	1	-0.6	66	67
TAT	-0.028	0.19	-10000	0	-0.6	18	18
CEBPB	0.04	0.017	-10000	0	-0.064	2	2
CEBPA	0.041	0.016	-10000	0	-0.066	1	1
TTR	0.036	0.17	-10000	0	-0.92	4	4
PKLR	-0.027	0.25	0.44	3	-0.58	41	44
APOA1	-0.13	0.48	-10000	0	-1.1	94	94
CPT1C	-0.031	0.24	0.43	1	-0.57	48	49
ALAS1	-0.007	0.18	-10000	0	-0.56	14	14
TFRC	-0.059	0.37	-10000	0	-0.95	66	66
FOXF1	0.036	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	-0.045	0.27	0.5	1	-0.6	61	62
HMGCS1	-0.037	0.26	0.5	3	-0.6	57	60
NR3C1	0.048	0.014	-10000	0	-10000	0	0
CPT1B	-0.038	0.24	-10000	0	-0.59	43	43
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.041	0.006	-10000	0	-10000	0	0
GCK	-0.034	0.24	0.55	1	-0.58	43	44
CREB1	0.02	0.096	-10000	0	-0.21	77	77
IGFBP1	-0.002	0.15	-10000	0	-0.44	9	9
PDX1	0.01	0.14	0.4	1	-0.29	28	29
UCP2	-0.059	0.31	0.48	8	-0.66	80	88
ALDOB	-0.008	0.23	-10000	0	-0.58	23	23
AFP	0.014	0.05	-10000	0	-10000	0	0
BDH1	-0.058	0.27	-10000	0	-0.61	68	68
HADH	-0.009	0.23	-10000	0	-0.5	49	49
F2	-0.039	0.31	-10000	0	-0.75	39	39
HNF1A	0.009	0.001	-10000	0	-10000	0	0
G6PC	0.026	0.09	-10000	0	-10000	0	0
SLC2A2	0.029	0.17	-10000	0	-0.43	1	1
INS	0.03	0.013	0.18	1	-0.06	4	5
FOXA1	0.056	0.016	-10000	0	-10000	0	0
FOXA3	0.02	0.12	-10000	0	-0.21	101	101
FOXA2	0.01	0.29	-10000	0	-0.6	40	40
ABCC8	-0.008	0.24	0.53	1	-0.56	28	29
ALB	0.014	0.051	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.019	0.005	0	40	-10000	0	40
MAP4K4	-0.002	0.081	0.2	3	-0.25	29	32
BAG4	0.037	0.013	-10000	0	0	63	63
PKC zeta/ceramide	0.032	0.031	-10000	0	-0.17	9	9
NFKBIA	0.037	0.014	-10000	0	0	66	66
BIRC3	0.026	0.02	-10000	0	0	213	213
BAX	0.013	0.054	-10000	0	-0.34	12	12
RIPK1	0.038	0.012	-10000	0	0	48	48
AKT1	0.003	0.12	0.67	18	-10000	0	18
BAD	0.001	0.03	0.18	4	-0.18	8	12
SMPD1	0.01	0.061	0.15	17	-0.17	28	45
RB1	-0.006	0.038	0.22	2	-0.17	11	13
FADD/Caspase 8	-0.005	0.11	0.24	7	-0.31	35	42
MAP2K4	-0.006	0.028	-10000	0	-0.18	8	8
NSMAF	0.038	0.013	-10000	0	0	55	55
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.005	0.032	0.17	6	-0.18	8	14
EGF	0.038	0.012	-10000	0	0	52	52
mol:ceramide	0.006	0.027	-10000	0	-0.18	9	9
MADD	0.041	0.006	-10000	0	0	12	12
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.016	0.009	0	135	-10000	0	135
ASAH1	0.033	0.017	-10000	0	0	121	121
negative regulation of cell cycle	-0.006	0.038	0.22	2	-0.16	11	13
cell proliferation	0.026	0.05	0.19	4	-0.18	8	12
BID	0.02	0.097	-10000	0	-0.59	5	5
MAP3K1	-0.002	0.028	-10000	0	-0.18	9	9
EIF2A	0.011	0.08	0.18	77	-0.18	13	90
TRADD	0.036	0.014	-10000	0	0	76	76
CRADD	0.041	0.006	-10000	0	0	12	12
MAPK3	-0.003	0.037	0.16	6	-0.18	8	14
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.009	0.043	0.17	5	-0.17	10	15
Cathepsin D/ceramide	0.029	0.032	-10000	0	-0.17	9	9
FADD	-0.001	0.084	0.22	6	-0.25	27	33
KSR1	-0.001	0.026	-10000	0	-0.18	8	8
MAPK8	0.008	0.047	-10000	0	-0.19	21	21
PRKRA	0.004	0.047	0.2	19	-0.18	9	28
PDGFA	0.04	0.007	-10000	0	0	18	18
TRAF2	0.04	0.009	-10000	0	0	25	25
IGF1	0.036	0.015	-10000	0	0	82	82
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.006	0.027	-10000	0	-0.18	9	9
CTSD	0.038	0.012	-10000	0	0	53	53
regulation of nitric oxide biosynthetic process	0.043	0.05	-10000	0	-0.14	35	35
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.029	0.054	0.2	4	-0.19	8	12
PRKCD	0.038	0.013	-10000	0	0	55	55
PRKCZ	0.042	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.016	0.009	0	135	-10000	0	135
RelA/NF kappa B1	0.043	0.05	-10000	0	-0.14	35	35
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.041	0.007	-10000	0	0	16	16
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.005	0.086	-10000	0	-0.26	27	27
TNFR1A/BAG4/TNF-alpha	0.059	0.046	-10000	0	-0.12	15	15
mol:Sphingosine-1-phosphate	-0.019	0.005	0	40	-10000	0	40
MAP2K1	-0.009	0.035	0.16	11	-0.17	7	18
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.041	0.006	-10000	0	0	10	10
CYCS	0.009	0.049	0.14	4	-0.18	10	14
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
NFKB1	0.035	0.015	-10000	0	0	85	85
TNFR1A/BAG4	0.044	0.038	-10000	0	-0.13	14	14
EIF2AK2	0	0.059	0.19	32	-0.17	13	45
TNF-alpha/TNFR1A/FAN	0.059	0.052	-10000	0	-0.14	20	20
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.006	0.14	-10000	0	-0.38	52	52
MAP2K2	-0.008	0.032	0.16	6	-0.18	8	14
SMPD3	-0.003	0.1	0.18	6	-0.29	51	57
TNF	0.04	0.009	-10000	0	0	25	25
PKC zeta/PAR4	0.06	0.013	-10000	0	-0.14	1	1
mol:PHOSPHOCHOLINE	0.004	0.034	0.12	3	-0.13	9	12
NF kappa B1/RelA/I kappa B alpha	0.081	0.082	-10000	0	-0.12	57	57
AIFM1	0.01	0.042	0.13	3	-0.18	9	12
BCL2	0.036	0.014	-10000	0	0	76	76

×

S1P3 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
PDGFRB	0.037	0.013	-10000	0	0	64	64
mol:S1P	0.001	0.007	-10000	0	-0.028	23	23
S1P1/S1P/Gi	0.007	0.08	-10000	0	-0.18	58	58
GNAO1	0.033	0.024	-10000	0	-0.05	19	19
S1P/S1P3/G12/G13	0.046	0.032	-10000	0	-0.066	24	24
AKT1	0.015	0.1	-10000	0	-0.45	21	21
AKT3	-0.02	0.23	-10000	0	-0.99	25	25
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	0.02	-10000	0	-0.047	19	19
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	23	23
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.041	0.007	-10000	0	0	15	15
mol:Ca2+	0.001	0.1	0.16	1	-0.27	45	46
MAPK3	-0.008	0.094	0.21	1	-0.26	46	47
MAPK1	-0.004	0.089	-10000	0	-0.27	38	38
JAK2	-0.018	0.11	0.2	4	-0.3	48	52
CXCR4	-0.01	0.099	0.19	3	-0.28	46	49
FLT1	0.04	0.022	-10000	0	-0.059	18	18
RhoA/GDP	0.029	0.014	-10000	0	-0.13	4	4
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
SRC	-0.002	0.098	0.22	15	-0.27	40	55
S1P/S1P3/Gi	0.001	0.1	0.16	1	-0.28	44	45
RAC1	0.039	0.01	-10000	0	0	35	35
RhoA/GTP	0.011	0.1	-10000	0	-0.26	45	45
VEGFA	0.003	0.01	0.018	92	-0.037	22	114
S1P/S1P2/Gi	-0.001	0.087	-10000	0	-0.25	38	38
VEGFR1 homodimer/VEGFA homodimer	0.036	0.032	-10000	0	-0.089	23	23
RHOA	0.041	0.007	-10000	0	0	14	14
S1P/S1P3/Gq	0.017	0.04	-10000	0	-0.15	26	26
GNAQ	0.038	0.012	-10000	0	0	50	50
GNAZ	0.038	0.02	-10000	0	-0.047	20	20
G12/G13	0.053	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	0.039	0.01	-10000	0	0	36	36
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	63	63
Rac1/GTP	0.01	0.1	-10000	0	-0.26	43	43

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.037	0.016	0.079	2	-0.057	3	5
HSPA8	0.039	0.01	-10000	0	0	34	34
SMAD3/SMAD4/ER alpha	0.065	0.091	0.26	10	-0.17	16	26
AKT1	0.04	0.017	-10000	0	-0.098	5	5
GSC	0.007	0.097	-10000	0	-0.96	3	3
NKX2-5	0.039	0.017	-10000	0	-0.053	13	13
muscle cell differentiation	-0.041	0.1	0.26	26	-10000	0	26
SMAD2-3/SMAD4/SP1	0.071	0.12	-10000	0	-0.2	9	9
SMAD4	0.036	0.046	-10000	0	-0.1	11	11
CBFB	0.036	0.015	-10000	0	0	83	83
SAP18	0.039	0.01	-10000	0	0	31	31
Cbp/p300/MSG1	0.06	0.056	-10000	0	-0.14	24	24
SMAD3/SMAD4/VDR	0.074	0.1	-10000	0	-0.22	12	12
MYC	0.021	0.022	0.12	4	-0.044	2	6
CDKN2B	-0.047	0.17	-10000	0	-1.1	7	7
AP1	0.004	0.091	-10000	0	-0.23	37	37
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.001	0.13	0.2	3	-0.31	52	55
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.012	0.063	-10000	0	-0.2	34	34
SP3	0.036	0.024	0.08	3	-0.053	33	36
CREB1	0.04	0.008	-10000	0	0	19	19
FOXH1	0.041	0.019	-10000	0	-0.058	17	17
SMAD3/SMAD4/GR	0.054	0.079	-10000	0	-0.15	20	20
GATA3	0.042	0.012	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	0.003	0.096	0.17	6	-0.27	37	43
MEF2C/TIF2	0.023	0.067	0.26	5	-0.22	15	20
endothelial cell migration	-0.032	0.1	1	4	-10000	0	4
MAX	0.029	0.027	0.098	3	-0.03	93	96
RBBP7	0.04	0.009	-10000	0	0	25	25
RBBP4	0.038	0.011	-10000	0	0	45	45
RUNX2	0.039	0.011	-10000	0	0	42	42
RUNX3	0.039	0.01	-10000	0	0	31	31
RUNX1	0.039	0.01	-10000	0	0	33	33
CTBP1	0.037	0.013	-10000	0	0	58	58
NR3C1	0.027	0.028	0.098	3	-0.023	121	124
VDR	0.037	0.013	-10000	0	0	58	58
CDKN1A	0.012	0.077	-10000	0	-0.63	3	3
KAT2B	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.081	0.06	-10000	0	-0.27	2	2
DCP1A	0.04	0.008	-10000	0	0	20	20
SKI	0.042	0.003	-10000	0	0	3	3
SERPINE1	0.031	0.1	-10000	0	-1	4	4
SMAD3/SMAD4/ATF2	0.063	0.074	-10000	0	-0.16	16	16
SMAD3/SMAD4/ATF3	0.061	0.068	-10000	0	-0.14	9	9
SAP30	0.038	0.013	-10000	0	0	55	55
Cbp/p300/PIAS3	0.062	0.058	-10000	0	-0.14	27	27
JUN	-0.001	0.086	0.18	4	-0.23	35	39
SMAD3/SMAD4/IRF7	0.071	0.07	-10000	0	-0.14	8	8
TFE3	0.039	0.033	0.11	1	-0.082	35	36
COL1A2	-0.091	0.25	-10000	0	-0.62	102	102
mesenchymal cell differentiation	-0.064	0.069	0.14	9	-10000	0	9
DLX1	0.04	0.008	-10000	0	0	22	22
TCF3	0.036	0.015	-10000	0	0	83	83
FOS	0.025	0.029	-10000	0	-0.05	26	26
SMAD3/SMAD4/Max	0.063	0.067	-10000	0	-0.14	7	7
Cbp/p300/SNIP1	0.058	0.056	-10000	0	-0.14	23	23
ZBTB17	0.039	0.011	0.1	4	-0.042	4	8
LAMC1	0.009	0.073	-10000	0	-0.26	24	24
TGIF2/HDAC complex/SMAD3/SMAD4	0.062	0.074	-10000	0	-0.15	16	16
IRF7	0.04	0.011	-10000	0	-10000	0	0
ESR1	0.046	0.037	0.12	89	0	92	181
HNF4A	0.039	0.01	-10000	0	0	35	35
MEF2C	-0.003	0.06	0.22	11	-0.23	15	26
SMAD2-3/SMAD4	0.071	0.073	-10000	0	-0.15	3	3
Cbp/p300/Src-1	0.059	0.061	-10000	0	-0.14	31	31
IGHV3OR16-13	0.009	0.061	-10000	0	-0.43	10	10
TGIF2/HDAC complex	0.038	0.012	-10000	0	0	48	48
CREBBP	0.038	0.013	-10000	0	-0.002	51	51
SKIL	0.025	0.02	-10000	0	0	221	221
HDAC1	0.038	0.012	-10000	0	0	54	54
HDAC2	0.038	0.012	-10000	0	0	48	48
SNIP1	0.039	0.011	-10000	0	0	40	40
GCN5L2	0.039	0.013	-10000	0	-0.003	47	47
SMAD3/SMAD4/TFE3	0.078	0.083	-10000	0	-0.16	22	22
MSG1/HSC70	0.053	0.027	-10000	0	-0.14	5	5
SMAD2	0.039	0.025	-10000	0	-0.064	20	20
SMAD3	0.036	0.045	-10000	0	-0.1	15	15
SMAD3/E2F4-5/DP1/p107/SMAD4	0.019	0.066	0.18	1	-0.2	20	21
SMAD2/SMAD2/SMAD4	-0.01	0.061	0.18	6	-0.18	41	47
NCOR1	0.037	0.013	-10000	0	0	57	57
NCOA2	0.037	0.014	-10000	0	0	69	69
NCOA1	0.04	0.009	-10000	0	0	28	28
MYOD/E2A	0.051	0.025	-10000	0	-0.14	1	1
SMAD2-3/SMAD4/SP1/MIZ-1	0.081	0.12	-10000	0	-0.23	4	4
IFNB1	0.013	0.051	0.27	3	-0.16	2	5
SMAD3/SMAD4/MEF2C	0.051	0.083	0.28	2	-0.22	14	16
CITED1	0.039	0.01	-10000	0	0	35	35
SMAD2-3/SMAD4/ARC105	0.068	0.067	-10000	0	-0.13	3	3
RBL1	0.038	0.012	-10000	0	0	51	51
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.023	0.075	-10000	0	-0.4	7	7
RUNX1-3/PEBPB2	0.063	0.044	-10000	0	-0.11	15	15
SMAD7	-0.001	0.14	-10000	0	-0.38	27	27
MYC/MIZ-1	0.017	0.058	0.2	4	-0.14	49	53
SMAD3/SMAD4	-0.006	0.11	0.26	1	-0.34	30	31
IL10	0.022	0.061	0.22	18	-10000	0	18
PIASy/HDAC complex	0.037	0.015	-10000	0	-0.038	5	5
PIAS3	0.04	0.01	-10000	0	-0.004	26	26
CDK2	0.038	0.014	-10000	0	-0.002	59	59
IL5	0.023	0.061	0.22	17	-10000	0	17
CDK4	0.038	0.015	-10000	0	-0.002	62	62
PIAS4	0.037	0.015	-10000	0	-0.038	5	5
ATF3	0.037	0.014	-10000	0	0	68	68
SMAD3/SMAD4/SP1	0.054	0.11	-10000	0	-0.18	26	26
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	0.06	0.22	11	-0.23	15	26
CEBPB	0.036	0.017	-10000	0	-0.061	5	5
SMAD3/SMAD4/DLX1	0.069	0.066	-10000	0	-0.14	7	7
MYOD1	0.04	0.008	-10000	0	0	19	19
SMAD3/SMAD4/HNF4	0.066	0.067	-10000	0	-0.14	7	7
SMAD3/SMAD4/GATA3	0.077	0.071	-10000	0	-0.17	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.025	0.02	-10000	0	0	221	221
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.086	0.084	-10000	0	-0.18	1	1
SMAD3/SMAD4/SP1-3	0.069	0.12	-10000	0	-0.21	24	24
MED15	0	0	-10000	0	-10000	0	0
SP1	0.018	0.066	-10000	0	-0.099	125	125
SIN3B	0.037	0.014	-10000	0	0	67	67
SIN3A	0.039	0.01	-10000	0	0	31	31
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.1	0.073	-10000	0	-0.17	12	12
ITGB5	-0.005	0.094	0.21	15	-0.26	32	47
TGIF/SIN3/HDAC complex/CtBP	0.006	0.091	-10000	0	-0.28	29	29
SMAD3/SMAD4/AR	0.042	0.09	-10000	0	-0.15	42	42
AR	0.033	0.017	-10000	0	0	119	119
negative regulation of cell growth	0.017	0.077	-10000	0	-0.26	17	17
SMAD3/SMAD4/MYOD	0.069	0.067	-10000	0	-0.14	7	7
E2F5	0.037	0.014	-10000	0	0	70	70
E2F4	0.036	0.015	-10000	0	0	79	79
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.097	0.081	-10000	0	-0.16	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	0.025	0.052	-10000	0	-0.29	7	7
TFDP1	0.038	0.012	-10000	0	0	53	53
SMAD3/SMAD4/AP1	0.033	0.11	0.26	3	-0.23	37	40
SMAD3/SMAD4/RUNX2	0.065	0.069	-10000	0	-0.14	9	9
TGIF2	0.038	0.012	-10000	0	0	48	48
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.039	0.01	-10000	0	0	34	34

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.07	0.067	-10000	0	-0.11	43	43
MAP4K1	0.039	0.011	-10000	0	0	43	43
MAP3K8	0.04	0.008	-10000	0	0	22	22
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.04	0.007	-10000	0	0	18	18
CRKL	0.039	0.01	-10000	0	0	35	35
MAP3K1	0.005	0.061	-10000	0	-0.23	17	17
JUN	-0.005	0.11	0.24	6	-0.51	22	28
MAP3K7	0.005	0.063	0.21	5	-0.22	18	23
GRAP2	0.038	0.013	-10000	0	0	55	55
CRK	0.038	0.011	-10000	0	0	45	45
MAP2K4	-0.005	0.077	-10000	0	-0.28	23	23
LAT	0.041	0.006	-10000	0	0	13	13
LCP2	0.034	0.016	-10000	0	0	100	100
MAPK8	-0.002	0.11	-10000	0	-0.55	22	22
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.016	0.066	-10000	0	-0.21	19	19
LAT/GRAP2/SLP76/HPK1/HIP-55	0.078	0.077	-10000	0	-0.12	41	41

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.016	0.009	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.061	0.061	0.18	72	-0.11	18	90
CDKN1B	0.016	0.09	0.22	9	-0.31	25	34
CDKN1A	0.009	0.086	0.21	17	-0.3	29	46
FRAP1	0.04	0.009	-10000	0	0	24	24
PRKDC	0.038	0.011	-10000	0	0	44	44
FOXO3	0.006	0.08	-10000	0	-0.3	32	32
AKT1	0.006	0.081	-10000	0	-0.32	30	30
BAD	0.041	0.005	-10000	0	0	9	9
AKT3	0.004	0.045	-10000	0	-0.2	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.08	-10000	0	-0.3	32	32
AKT1/ASK1	0.027	0.089	-10000	0	-0.29	34	34
BAD/YWHAZ	0.055	0.044	-10000	0	-0.12	7	7
RICTOR	0.037	0.014	-10000	0	0	66	66
RAF1	0.04	0.008	-10000	0	0	20	20
JNK cascade	-0.026	0.086	0.28	34	-10000	0	34
TSC1	0.002	0.079	0.23	2	-0.3	29	31
YWHAZ	0.034	0.016	-10000	0	0	104	104
AKT1/RAF1	0.034	0.094	-10000	0	-0.31	32	32
EP300	0.036	0.014	-10000	0	0	72	72
mol:GDP	0.006	0.082	-10000	0	-0.31	32	32
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0	0.081	-10000	0	-0.3	33	33
YWHAQ	0.04	0.009	-10000	0	0	26	26
TBC1D4	0.006	0.031	0.24	5	-0.17	6	11
MAP3K5	0.037	0.014	-10000	0	0	70	70
MAPKAP1	0.04	0.009	-10000	0	0	25	25
negative regulation of cell cycle	-0.029	0.082	0.32	10	-0.22	4	14
YWHAH	0.038	0.012	-10000	0	0	54	54
AKT1S1	0.007	0.084	0.26	5	-0.31	28	33
CASP9	0.001	0.079	-10000	0	-0.31	30	30
YWHAB	0.038	0.011	-10000	0	0	44	44
p27Kip1/KPNA1	0.036	0.11	0.28	7	-0.31	29	36
GBL	0.04	0.009	-10000	0	0	24	24
PDK1/Src/Hsp90	0.05	0.022	-10000	0	-0.11	5	5
YWHAE	0.038	0.012	-10000	0	0	50	50
SRC	0.039	0.01	-10000	0	0	31	31
AKT2/p21CIP1	0.012	0.079	0.21	17	-0.28	26	43
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.092	-10000	0	-0.35	26	26
CHUK	-0.001	0.081	-10000	0	-0.31	31	31
BAD/BCL-XL	0.028	0.087	-10000	0	-0.3	28	28
mTORC2	0.078	0.062	-10000	0	-0.12	32	32
AKT2	0.015	0.023	-10000	0	-0.2	6	6
FOXO1-3a-4/14-3-3 family	0.03	0.1	0.26	3	-0.38	12	15
PDPK1	0.04	0.009	-10000	0	0	27	27
MDM2	0.005	0.088	0.2	13	-0.31	32	45
MAPKKK cascade	-0.034	0.092	0.3	32	-10000	0	32
MDM2/Cbp/p300	0.039	0.11	0.34	3	-0.31	32	35
TSC1/TSC2	-0.003	0.082	0.29	4	-0.3	32	36
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.1	0.33	3	-0.3	32	35
glucose import	-0.004	0.035	0.21	10	-0.16	6	16
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.022	0.087	0.28	1	-0.32	10	11
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.004	0.033	0.21	9	-0.16	6	15
GSK3A	0.003	0.081	0.27	2	-0.31	30	32
FOXO1	0.006	0.08	-10000	0	-0.3	32	32
GSK3B	0.007	0.089	0.24	5	-0.3	32	37
SFN	0.035	0.015	-10000	0	0	84	84
G1/S transition of mitotic cell cycle	0.007	0.096	0.32	9	-0.3	30	39
p27Kip1/14-3-3 family	0.021	0.078	-10000	0	-0.33	11	11
PRKACA	0.035	0.015	-10000	0	0	87	87
KPNA1	0.039	0.01	-10000	0	0	36	36
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0.04	0.009	-10000	0	0	26	26
RHEB	0.037	0.013	-10000	0	0	62	62
CREBBP	0.038	0.012	-10000	0	0	49	49

×

S1P5 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
telencephalon oligodendrocyte cell migration	-0.007	0.083	0.22	34	-10000	0	34
GNAI2	0.041	0.006	-10000	0	0	13	13
S1P/S1P5/G12	0.026	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	0.008	0.085	-10000	0	-0.23	34	34
negative regulation of cAMP metabolic process	-0.005	0.077	-10000	0	-0.18	66	66
GNAZ	0.039	0.011	-10000	0	0	38	38
GNAI3	0.038	0.012	-10000	0	0	46	46
GNA12	0.039	0.01	-10000	0	0	36	36
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.005	0.077	-10000	0	-0.18	66	66
RhoA/GDP	0.029	0.014	-10000	0	-0.13	4	4
RHOA	0.041	0.007	-10000	0	0	14	14
GNAI1	0.035	0.016	-10000	0	0	94	94

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.038	0.012	-10000	0	0	47	47
NFATC1	0.02	0.1	0.24	2	-0.31	19	21
NFATC2	0.026	0.058	0.16	9	-0.22	10	19
NFATC3	0.025	0.016	-10000	0	-10000	0	0
YWHAE	0.038	0.012	-10000	0	0	50	50
Calcineurin A alpha-beta B1/CABIN1	-0.002	0.085	0.18	1	-0.26	26	27
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	0.029	0.097	-10000	0	-0.25	19	19
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	-0.11	6	6
CaM/Ca2+	0.029	0.019	-10000	0	-0.11	6	6
BAX	0.04	0.008	-10000	0	0	20	20
MAPK14	0.04	0.009	-10000	0	0	28	28
BAD	0.041	0.005	-10000	0	0	9	9
CABIN1/MEF2D	0.014	0.089	-10000	0	-0.25	24	24
Calcineurin A alpha-beta B1/BCL2	0.036	0.014	-10000	0	0	76	76
FKBP8	0.036	0.014	-10000	0	0	73	73
activation-induced cell death of T cells	-0.014	0.088	0.25	24	-10000	0	24
KPNB1	0.04	0.009	-10000	0	0	29	29
KPNA2	0.035	0.015	-10000	0	0	84	84
XPO1	0.039	0.011	-10000	0	0	39	39
SFN	0.035	0.015	-10000	0	0	84	84
MAP3K8	0.041	0.008	-10000	0	0	22	22
NFAT4/CK1 alpha	0.027	0.045	0.19	1	-0.13	17	18
MEF2D/NFAT1/Cbp/p300	0.072	0.089	0.24	2	-0.2	11	13
CABIN1	-0.002	0.085	0.18	1	-0.27	26	27
CALM1	0.04	0.01	-10000	0	0	30	30
RAN	0.041	0.006	-10000	0	0	11	11
MAP3K1	0.036	0.015	-10000	0	0	78	78
CAMK4	0.037	0.013	-10000	0	0	65	65
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.041	0.007	-10000	0	0	17	17
YWHAH	0.038	0.012	-10000	0	0	54	54
Calcineurin A alpha-beta B1/AKAP79/PKA	0.05	0.026	-10000	0	-0.14	2	2
YWHAB	0.038	0.011	-10000	0	0	44	44
MAPK8	0.04	0.01	-10000	0	0	29	29
MAPK9	0.039	0.011	-10000	0	0	39	39
YWHAG	0.04	0.009	-10000	0	0	26	26
FKBP1A	0.039	0.011	-10000	0	0	39	39
NFAT1-c-4/YWHAQ	0.036	0.11	0.26	2	-0.3	20	22
PRKCH	0.039	0.011	-10000	0	0	41	41
CABIN1/Cbp/p300	0.043	0.052	-10000	0	-0.16	24	24
CASP3	0.037	0.014	-10000	0	0	70	70
PIM1	0.038	0.011	-10000	0	0	44	44
Calcineurin A alpha-beta B1/FKBP12/FK506	0.027	0.011	-10000	0	-0.1	2	2
apoptosis	0.02	0.037	-10000	0	-0.2	11	11
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.077	-10000	0	-0.26	18	18
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.039	0.011	-10000	0	0	38	38
JNK2/NFAT4	0.025	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	55	55
NUP214	0.04	0.01	-10000	0	0	32	32
PRKCZ	0.043	0.002	-10000	0	-10000	0	0
PRKCA	0.035	0.016	-10000	0	0	91	91
PRKCG	0.041	0.005	-10000	0	0	7	7
PRKCQ	0.035	0.016	-10000	0	0	93	93
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	0.039	0.011	-10000	0	0	40	40
NFATc/JNK1	0.034	0.11	0.26	2	-0.3	19	21
CaM/Ca2+/FKBP38	0.047	0.027	-10000	0	-0.13	4	4
FKBP12/FK506	0.028	0.012	-10000	0	-0.13	2	2
CSNK1A1	0.017	0.017	0.092	6	-0.044	17	23
CaM/Ca2+/CAMK IV	0.047	0.028	-10000	0	-0.11	7	7
NFATc/ERK1	0.035	0.1	0.26	2	-0.3	17	19
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.026	0.098	-10000	0	-0.24	22	22
NR4A1	0.016	0.073	0.2	16	-0.22	19	35
GSK3B	0.04	0.01	-10000	0	0	29	29
positive T cell selection	0.025	0.016	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.023	0.047	0.12	6	-0.19	11	17
RCH1/ KPNB1	0.036	0.063	-10000	0	-0.14	58	58
YWHAQ	0.04	0.009	-10000	0	0	26	26
PRKACA	0.036	0.016	-10000	0	0	87	87
AKAP5	0.04	0.007	-10000	0	0	18	18
MEF2D	0.041	0.009	-10000	0	0	24	24
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.034	0.016	-10000	0	0	104	104
NFATc/p38 alpha	0.036	0.1	0.26	2	-0.3	18	20
CREBBP	0.039	0.013	-10000	0	-0.001	50	50
BCL2	0.036	0.014	-10000	0	0	76	76

×

S1P4 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
GNAO1	0.034	0.016	-10000	0	0	101	101
CDC42/GTP	0.008	0.084	-10000	0	-0.22	34	34
PLCG1	-0.013	0.071	-10000	0	-0.18	66	66
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.041	0.006	-10000	0	0	13	13
GNAI3	0.038	0.012	-10000	0	0	46	46
G12/G13	0.053	0.03	-10000	0	-0.14	9	9
cell migration	0.007	0.082	-10000	0	-0.22	34	34
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	65	65
MAPK1	-0.007	0.064	-10000	0	-0.17	57	57
S1P/S1P5/Gi	-0.005	0.077	-10000	0	-0.18	66	66
GNAI1	0.035	0.016	-10000	0	0	94	94
CDC42/GDP	0.029	0.013	-10000	0	-0.13	3	3
S1P/S1P5/G12	0.026	0.007	-10000	0	-10000	0	0
RHOA	-0.012	0.037	0.18	16	-0.17	1	17
S1P/S1P4/Gi	-0.005	0.077	-10000	0	-0.18	66	66
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.039	0.011	-10000	0	0	38	38
S1P/S1P4/G12/G13	0.046	0.024	-10000	0	-0.098	9	9
GNA12	0.039	0.01	-10000	0	0	36	36
GNA13	0.04	0.009	-10000	0	0	28	28
CDC42	0.04	0.008	-10000	0	0	22	22

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.053	0.092	-10000	0	-0.23	26	26
Ran/GTP/Exportin 1/HDAC1	-0.03	0.033	-10000	0	-0.12	47	47
NF kappa B1 p50/RelA/I kappa B alpha	0.027	0.1	0.24	1	-0.31	26	27
SUMO1	0.041	0.006	-10000	0	0	13	13
ZFPM1	0.035	0.016	-10000	0	0	92	92
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
FKBP3	0.039	0.01	-10000	0	0	34	34
Histones	0.069	0.086	0.24	1	-0.24	12	13
YY1/LSF	0.013	0.082	-10000	0	-0.23	40	40
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	11	11
I kappa B alpha/HDAC3	0.017	0.06	-10000	0	-0.18	37	37
I kappa B alpha/HDAC1	0.031	0.09	0.22	1	-0.26	33	34
SAP18	0.039	0.01	-10000	0	0	31	31
RELA	0.018	0.085	0.22	3	-0.38	12	15
HDAC1/Smad7	0.062	0.053	-10000	0	-0.12	31	31
RANGAP1	0.038	0.013	-10000	0	0	55	55
HDAC3/TR2	0.048	0.059	0.22	1	-0.23	11	12
NuRD/MBD3 Complex	0.009	0.1	-10000	0	-0.28	34	34
NF kappa B1 p50/RelA	0.024	0.1	0.25	1	-0.28	30	31
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.039	0.01	-10000	0	0	34	34
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	0.004	0.11	-10000	0	-0.27	44	44
RBBP7	0.04	0.009	-10000	0	0	25	25
NPC	0.02	0.022	-10000	0	-0.085	23	23
RBBP4	0.038	0.011	-10000	0	0	45	45
MAX	0.041	0.007	-10000	0	0	16	16
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.008	-10000	0	0	23	23
NFKBIA	0.009	0.07	-10000	0	-0.27	29	29
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.005	0.092	-10000	0	-0.32	24	24
SIN3 complex	0.074	0.055	-10000	0	-0.12	11	11
SMURF1	0.04	0.008	-10000	0	0	19	19
CHD3	0.038	0.012	-10000	0	0	49	49
SAP30	0.038	0.013	-10000	0	0	55	55
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.038	0.013	-10000	0	0	57	57
YY1/HDAC3	0.018	0.076	-10000	0	-0.24	25	25
YY1/HDAC2	0.016	0.076	-10000	0	-0.21	38	38
YY1/HDAC1	0.013	0.078	-10000	0	-0.22	37	37
NuRD/MBD2 Complex (MeCP1)	0.011	0.099	0.17	5	-0.29	32	37
PPARG	0.031	0.068	0.2	6	-0.21	25	31
HDAC8/hEST1B	0.042	0.036	-10000	0	-0.11	20	20
UBE2I	0.04	0.009	-10000	0	0	26	26
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.008	-10000	0	0	23	23
TNFRSF1A	0.036	0.015	-10000	0	0	82	82
HDAC3/SMRT (N-CoR2)	0.049	0.058	0.22	1	-0.2	15	16
MBD3L2	0.039	0.011	-10000	0	0	41	41
ubiquitin-dependent protein catabolic process	0.061	0.052	-10000	0	-0.12	31	31
CREBBP	0.038	0.012	-10000	0	0	49	49
NuRD/MBD3/MBD3L2 Complex	0.008	0.1	0.19	8	-0.27	43	51
HDAC1	0.038	0.012	-10000	0	0	54	54
HDAC3	0.022	0.036	-10000	0	-0.3	4	4
HDAC2	0.038	0.012	-10000	0	0	48	48
YY1	0.006	0.056	-10000	0	-0.24	23	23
HDAC8	0.04	0.009	-10000	0	0	26	26
SMAD7	0.038	0.012	-10000	0	0	46	46
NCOR2	0.04	0.009	-10000	0	0	26	26
MXD1	0.041	0.007	-10000	0	0	17	17
STAT3	0.01	0.064	-10000	0	-0.25	29	29
NFKB1	0.035	0.015	-10000	0	0	85	85
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.04	0.009	-10000	0	0	30	30
YY1/LSF/HDAC1	0.023	0.091	-10000	0	-0.22	43	43
YY1/SAP30/HDAC1	0.025	0.084	-10000	0	-0.2	38	38
EP300	0.036	0.014	-10000	0	0	72	72
STAT3 (dimer non-phopshorylated)	0.01	0.064	-10000	0	-0.24	29	29
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.07	-10000	0	-0.27	29	29
histone deacetylation	0.011	0.098	0.17	5	-0.28	32	37
STAT3 (dimer non-phopshorylated)/HDAC3	0.022	0.082	-10000	0	-0.29	19	19
nuclear export	-0.041	0.036	0.11	20	-10000	0	20
PRKACA	0.035	0.015	-10000	0	0	87	87
GATAD2B	0.038	0.012	-10000	0	0	49	49
GATAD2A	0.037	0.013	-10000	0	0	59	59
GATA2/HDAC3	0.048	0.057	0.22	1	-0.22	10	11
GATA1/HDAC1	0.05	0.043	-10000	0	-0.14	26	26
GATA1/HDAC3	0.052	0.058	0.22	1	-0.24	10	11
CHD4	0.036	0.014	-10000	0	0	77	77
TNF-alpha/TNFR1A	0.047	0.038	-10000	0	-0.14	15	15
SIN3/HDAC complex/Mad/Max	0.009	0.093	-10000	0	-0.3	26	26
NuRD Complex	0.004	0.1	0.19	8	-0.27	40	48
positive regulation of chromatin silencing	0.066	0.083	-10000	0	-0.23	12	12
SIN3B	0.037	0.014	-10000	0	0	67	67
MTA2	0.041	0.005	-10000	0	0	9	9
SIN3A	0.039	0.01	-10000	0	0	31	31
XPO1	0.039	0.011	-10000	0	0	39	39
SUMO1/HDAC1	0.037	0.064	-10000	0	-0.18	22	22
HDAC complex	0.072	0.077	-10000	0	-0.14	54	54
GATA1/Fog1	0.052	0.023	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.057	0.061	-10000	0	-0.13	43	43
TNF	0.04	0.009	-10000	0	0	25	25
negative regulation of cell growth	0.009	0.092	-10000	0	-0.3	26	26
NuRD/MBD2/PRMT5 Complex	0.011	0.099	0.17	5	-0.29	32	37
Ran/GTP/Exportin 1	0.038	0.07	0.18	1	-0.18	33	34
NF kappa B/RelA/I kappa B alpha	0.017	0.082	-10000	0	-0.3	23	23
SIN3/HDAC complex/NCoR1	-0.001	0.096	0.17	1	-0.27	38	39
TFCP2	0.039	0.011	-10000	0	0	38	38
NR2C1	0.039	0.011	-10000	0	0	40	40
MBD3	0.036	0.014	-10000	0	0	72	72
MBD2	0.039	0.011	-10000	0	0	42	42

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.055	0.051	-10000	0	-0.11	23	23
fibroblast growth factor receptor signaling pathway	0.055	0.05	-10000	0	-0.11	23	23
LAMA1	0.034	0.017	-10000	0	0	108	108
PRNP	0.037	0.013	-10000	0	0	59	59
GPC1/SLIT2	0.018	0.072	-10000	0	-0.14	90	90
SMAD2	-0.021	0.036	0.19	8	-0.19	1	9
GPC1/PrPc/Cu2+	0.041	0.041	-10000	0	-0.11	32	32
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	0.057	0.018	-10000	0	-0.14	1	1
APP/GPC1	0.047	0.044	-10000	0	-0.14	25	25
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.017	0.028	0.19	7	-0.12	1	8
FLT1	0.039	0.01	-10000	0	0	36	36
GPC1/TGFB/TGFBR1/TGFBR2	0.068	0.043	-10000	0	-0.12	17	17
SERPINC1	0.04	0.008	-10000	0	0	23	23
FYN	-0.015	0.029	0.19	7	-0.12	1	8
FGR	-0.018	0.028	0.19	7	-0.12	1	8
positive regulation of MAPKKK cascade	0.005	0.074	0.21	18	-0.22	12	30
SLIT2	0.028	0.02	-10000	0	0	181	181
GPC1/NRG	0.049	0.026	-10000	0	-0.14	1	1
NRG1	0.035	0.015	-10000	0	0	90	90
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.049	0.024	-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	0.05	-10000	0	-0.11	23	23
BMP signaling pathway	-0.04	0.009	0	29	-10000	0	29
SRC	-0.018	0.028	0.19	7	-0.12	1	8
TGFBR1	0.04	0.008	-10000	0	0	22	22
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.037	0.014	-10000	0	0	67	67
GPC1	0.04	0.009	-10000	0	0	29	29
TGFBR1 (dimer)	0.04	0.008	-10000	0	0	22	22
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.016	0.024	0.19	4	-0.12	1	5
HCK	-0.016	0.027	0.19	6	-10000	0	6
FGF2	0.038	0.012	-10000	0	0	46	46
FGFR1	0.033	0.017	-10000	0	0	121	121
VEGFR1 homodimer	0.039	0.01	-10000	0	0	36	36
TGFBR2	0.039	0.011	-10000	0	0	38	38
cell death	0.047	0.044	-10000	0	-0.14	25	25
ATIII/GPC1	0.056	0.019	-10000	0	-0.14	1	1
PLA2G2A/GPC1	0.051	0.027	-10000	0	-0.14	3	3
LCK	-0.018	0.028	0.19	7	-10000	0	7
neuron differentiation	0.049	0.026	-10000	0	-0.14	1	1
PrPc/Cu2+	0.02	0.037	-10000	0	-0.13	31	31
APP	0.038	0.012	-10000	0	0	47	47
TGFBR2 (dimer)	0.039	0.011	-10000	0	0	38	38

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.015	0.088	-10000	0	-0.38	23	23
Crk/p130 Cas/Paxillin	0.005	0.039	-10000	0	-0.17	8	8
JUN	0.002	0.062	0.18	5	-0.23	11	16
HRAS	0.04	0.009	-10000	0	0	29	29
RET51/GFRalpha1/GDNF/GRB10	0.089	0.04	-10000	0	-0.11	5	5
RAP1A	0.039	0.01	-10000	0	0	35	35
FRS2	0.039	0.01	-10000	0	0	37	37
RAP1A/GDP	0.024	0.03	-10000	0	-0.13	21	21
RET51/GFRalpha1/GDNF/DOK1	0.089	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	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.011	-10000	0	0	45	45
RET9/GFRalpha1/GDNF/Enigma	0.062	0.035	-10000	0	-0.1	2	2
RHOA	0.041	0.007	-10000	0	0	14	14
RAP1A/GTP	0.074	0.051	-10000	0	-0.1	15	15
GRB7	0.037	0.013	-10000	0	0	62	62
RET51/GFRalpha1/GDNF	0.077	0.047	-10000	0	-0.11	3	3
MAPKKK cascade	0.048	0.045	-10000	0	-0.15	4	4
BCAR1	0.036	0.014	-10000	0	0	74	74
RET9/GFRalpha1/GDNF/IRS1	0.063	0.036	-10000	0	-0.1	5	5
lamellipodium assembly	0.029	0.051	-10000	0	-0.17	5	5
RET51/GFRalpha1/GDNF/SHC	0.088	0.039	-10000	0	-0.11	2	2
PIK3CA	0.03	0.019	-10000	0	0	150	150
RET9/GFRalpha1/GDNF/SHC	0.062	0.035	-10000	0	-0.1	2	2
RET9/GFRalpha1/GDNF/Shank3	0.066	0.032	-10000	0	-0.1	1	1
MAPK3	-0.008	0.065	0.18	42	-10000	0	42
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	0.002	0.06	0.17	39	-0.21	4	43
DOK5	0.022	0.021	-10000	0	0	266	266
GFRA1	0.037	0.013	-10000	0	0	64	64
MAPK8	0.011	0.06	-10000	0	-0.16	34	34
HRAS/GTP	0.08	0.048	-10000	0	-0.13	8	8
tube development	0.063	0.029	0.24	4	-0.1	2	6
MAPK1	-0.008	0.063	0.18	41	-10000	0	41
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.021	0.048	-10000	0	-0.17	25	25
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
SRC	0.039	0.01	-10000	0	0	31	31
PDLIM7	0.039	0.01	-10000	0	0	35	35
RET51/GFRalpha1/GDNF/Dok6	0.091	0.055	-10000	0	-0.11	1	1
SHC1	0.04	0.009	-10000	0	0	29	29
RET51/GFRalpha1/GDNF/Dok4	0.085	0.041	-10000	0	-0.11	1	1
RET51/GFRalpha1/GDNF/Dok5	0.041	0.079	-10000	0	-0.11	82	82
PRKCA	0.035	0.016	-10000	0	0	91	91
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
CREB1	0.035	0.064	-10000	0	-0.38	5	5
PIK3R1	0.034	0.016	-10000	0	0	106	106
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.024	0.034	-10000	0	-0.15	10	10
RET51/GFRalpha1/GDNF/Grb7	0.084	0.045	-10000	0	-0.11	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.04	0.007	-10000	0	0	18	18
DOK4	0.038	0.012	-10000	0	0	50	50
JNK cascade	0.002	0.061	0.18	5	-0.23	11	16
RET9/GFRalpha1/GDNF/FRS2	0.06	0.04	-10000	0	-0.1	10	10
SHANK3	0.042	0.002	-10000	0	0	1	1
RASA1	0.036	0.014	-10000	0	0	73	73
NCK1	0.036	0.014	-10000	0	0	77	77
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.023	0.038	-10000	0	-0.14	24	24
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.026	0.051	-10000	0	-0.17	25	25
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	0.041	0.064	0.26	5	-0.23	4	9
SOS1	0.038	0.013	-10000	0	0	57	57
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.085	0.033	-10000	0	-0.1	2	2
GRB10	0.04	0.008	-10000	0	0	23	23
activation of MAPKK activity	0.029	0.054	0.16	1	-0.17	25	26
RET51/GFRalpha1/GDNF/FRS2	0.086	0.045	-10000	0	-0.11	10	10
GAB1	0.038	0.012	-10000	0	0	49	49
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.01	-10000	0	0	36	36
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.03	0.037	-10000	0	-0.15	10	10
RET51/GFRalpha1/GDNF/PKC alpha	0.076	0.058	-10000	0	-0.11	29	29
GRB2	0.041	0.007	-10000	0	0	14	14
PRKACA	0.035	0.015	-10000	0	0	87	87
GDNF	0.039	0.011	-10000	0	0	40	40
RAC1	0.039	0.01	-10000	0	0	35	35
RET51/GFRalpha1/GDNF/IRS1	0.09	0.039	-10000	0	-0.11	5	5
Rac1/GTP	0.04	0.063	0.2	3	-0.21	4	7
RET9/GFRalpha1/GDNF	0.046	0.023	-10000	0	-0.11	1	1
GFRalpha1/GDNF	0.051	0.025	-10000	0	-0.14	1	1

×

Atypical NF-kappaB 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
BCL3/RelA	0.055	0.027	-10000	0	-0.16	5	5
FBXW11	0.04	0.008	-10000	0	0	23	23
NF kappa B1 p50/c-Rel	0.027	0.037	-10000	0	-0.12	27	27
NF kappa B1 p50/RelA/I kappa B alpha	0.021	0.076	0.19	1	-0.22	21	22
NFKBIA	0.006	0.062	-10000	0	-0.25	9	9
MAPK14	0.04	0.009	-10000	0	0	28	28
NF kappa B1 p105/p50	0.026	0.039	-10000	0	-0.12	28	28
ARRB2	0.014	0.028	-10000	0	-0.2	9	9
REL	0.04	0.007	-10000	0	0	18	18
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.025	0.038	-10000	0	-0.12	28	28
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.039	-10000	0	-0.12	29	29
PIK3CA	0.03	0.019	-10000	0	0	150	150
NF kappa B1 p50 dimer	0.02	0.04	-10000	0	-0.14	29	29
PIK3R1	0.034	0.016	-10000	0	0	106	106
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	-0.17	13	15
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.024	0.082	-10000	0	-0.22	21	21
SRC	0.039	0.01	-10000	0	0	31	31
PI3K	0.024	0.062	-10000	0	-0.15	47	47
NF kappa B1 p50/RelA	0.013	0.052	0.14	2	-0.17	13	15
IKBKB	0.038	0.011	-10000	0	0	44	44
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.008	-10000	0	0	23	23
SYK	0.037	0.014	-10000	0	0	67	67
I kappa B alpha/PIK3R1	0.018	0.068	0.19	1	-0.22	14	15
cell death	0.02	0.076	-10000	0	-0.22	21	21
NF kappa B1 p105/c-Rel	0.027	0.037	-10000	0	-0.12	27	27
LCK	0.04	0.009	-10000	0	0	28	28
BCL3	0.039	0.011	-10000	0	0	39	39

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.014	0.079	-10000	0	-0.15	92	92
AKT1	0.011	0.1	0.28	9	-0.32	16	25
PTK2B	-0.011	0.08	0.2	26	-0.31	7	33
VEGFR2 homodimer/Frs2	0.032	0.058	-10000	0	-0.37	4	4
CAV1	0.036	0.015	-10000	0	0	80	80
CALM1	0.04	0.009	-10000	0	0	30	30
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.031	0.058	-10000	0	-0.36	4	4
endothelial cell proliferation	0.033	0.095	0.27	11	-0.35	5	16
mol:Ca2+	0.02	0.064	0.2	24	-0.31	6	30
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.047	0.079	-10000	0	-0.22	19	19
RP11-342D11.1	-0.005	0.058	0.17	25	-0.35	4	29
CDH5	0.036	0.015	-10000	0	0	79	79
VEGFA homodimer	0.065	0.049	-10000	0	-0.11	32	32
SHC1	0.04	0.009	-10000	0	0	29	29
SHC2	0.037	0.014	-10000	0	0	69	69
HRAS/GDP	0.039	0.067	-10000	0	-0.26	8	8
SH2D2A	0.04	0.009	-10000	0	0	30	30
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.05	0.082	0.31	1	-0.37	6	7
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.034	0.053	-10000	0	-0.31	4	4
VEGFR1 homodimer	0.039	0.01	-10000	0	0	36	36
SHC/GRB2/SOS1	0.072	0.084	-10000	0	-0.27	8	8
GRB10	0.02	0.069	0.28	1	-0.34	8	9
PTPN11	0.04	0.009	-10000	0	0	29	29
GRB2	0.041	0.007	-10000	0	0	14	14
PAK1	0.037	0.014	-10000	0	0	66	66
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.051	0.089	-10000	0	-0.21	21	21
HRAS	0.04	0.009	-10000	0	0	29	29
VEGF/Rho/ROCK1/Integrin Complex	-0.014	0.11	-10000	0	-0.26	73	73
HIF1A	0.039	0.011	-10000	0	0	43	43
FRS2	0.039	0.01	-10000	0	0	37	37
oxygen and reactive oxygen species metabolic process	0.045	0.077	-10000	0	-0.21	19	19
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	0.061	-10000	0	-0.29	6	6
mol:GDP	0.056	0.075	-10000	0	-0.25	9	9
mol:NADP	0.038	0.079	0.29	5	-0.34	7	12
eNOS/Hsp90	0.035	0.074	0.29	4	-0.32	7	11
PIK3R1	0.034	0.016	-10000	0	0	106	106
mol:IP3	0.02	0.065	0.2	24	-0.31	6	30
HIF1A/ARNT	0.049	0.045	-10000	0	-0.14	25	25
SHB	0.041	0.007	-10000	0	0	16	16
VEGFA	0.002	0.005	-10000	0	-0.041	6	6
VEGFC	0.036	0.015	-10000	0	0	78	78
FAK1/Vinculin	0.013	0.13	0.28	9	-0.32	32	41
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	0.024	0.088	-10000	0	-0.21	33	33
PTPN6	0.037	0.013	-10000	0	0	63	63
EPAS1	0.043	0.031	-10000	0	-0.27	3	3
mol:L-citrulline	0.038	0.079	0.29	5	-0.34	7	12
ITGAV	0.033	0.017	-10000	0	0	115	115
PIK3CA	0.03	0.019	-10000	0	0	150	150
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.055	0.07	-10000	0	-0.31	5	5
VEGFR2 homodimer/VEGFA homodimer	0.043	0.061	-10000	0	-0.29	7	7
VEGFR2/3 heterodimer	0.033	0.057	-10000	0	-0.37	4	4
VEGFB	0.039	0.011	-10000	0	0	42	42
MAPK11	-0.001	0.071	0.25	9	-0.33	7	16
VEGFR2 homodimer	0.022	0.044	-10000	0	-0.43	4	4
FLT1	0.039	0.01	-10000	0	0	36	36
NEDD4	0.041	0.014	-10000	0	-0.058	5	5
MAPK3	-0.002	0.071	0.23	11	-0.3	6	17
MAPK1	-0.002	0.072	0.24	10	-0.32	6	16
VEGFA145/NRP2	0.016	0.045	-10000	0	-0.12	54	54
VEGFR1/2 heterodimer	0.032	0.058	-10000	0	-0.31	6	6
KDR	0.022	0.044	-10000	0	-0.43	4	4
VEGFA165/NRP1/VEGFR2 homodimer	0.033	0.073	-10000	0	-0.21	19	19
SRC	0.039	0.01	-10000	0	0	31	31
platelet activating factor biosynthetic process	-0.001	0.073	0.24	10	-0.34	5	15
PI3K	0.012	0.081	0.25	1	-0.32	8	9
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.025	0.062	-10000	0	-0.26	9	9
FES	0.021	0.065	0.2	26	-0.35	4	30
GAB1	0.017	0.083	0.26	3	-0.32	15	18
VEGFR2 homodimer/VEGFA homodimer/Src	0.034	0.053	-10000	0	-0.31	4	4
CTNNB1	0.039	0.01	-10000	0	0	32	32
SOS1	0.038	0.013	-10000	0	0	57	57
ARNT	0.041	0.006	-10000	0	0	13	13
eNOS/Caveolin-1	0.044	0.082	0.33	3	-0.34	7	10
VEGFR2 homodimer/VEGFA homodimer/Yes	0.027	0.062	-10000	0	-0.28	7	7
PI3K/GAB1	0.024	0.11	0.26	5	-0.33	15	20
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.05	0.084	-10000	0	-0.21	12	12
PRKACA	0.035	0.015	-10000	0	0	87	87
VEGFR2/3 heterodimer/VEGFC homodimer	0.051	0.068	-10000	0	-0.32	5	5
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.021	0.065	0.2	25	-0.37	4	29
actin cytoskeleton reorganization	0.034	0.052	-10000	0	-0.31	4	4
PTK2	-0.004	0.11	0.26	4	-0.33	30	34
EDG1	0.02	0.062	0.24	2	-0.36	4	6
mol:DAG	0.02	0.065	0.2	24	-0.31	6	30
CaM/Ca2+	0.035	0.066	0.25	2	-0.29	6	8
MAP2K3	-0.007	0.061	0.18	24	-0.36	4	28
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.047	0.072	0.24	5	-0.34	8	13
PLCG1	0.021	0.065	0.2	24	-0.32	6	30
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.06	0.064	-10000	0	-0.29	4	4
IQGAP1	0.037	0.014	-10000	0	0	67	67
YES1	0.037	0.013	-10000	0	0	59	59
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.03	0.061	-10000	0	-0.3	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.033	0.053	-10000	0	-0.34	4	4
cell migration	0.001	0.13	0.26	10	-0.35	35	45
mol:PI-3-4-5-P3	0.012	0.078	0.24	1	-0.3	8	9
FYN	0.034	0.016	-10000	0	0	102	102
VEGFB/NRP1	0.026	0.062	0.21	8	-0.28	6	14
mol:NO	0.038	0.079	0.29	5	-0.34	7	12
PXN	0.041	0.007	-10000	0	0	14	14
HRAS/GTP	0.018	0.056	-10000	0	-0.26	8	8
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.025	0.06	-10000	0	-0.34	8	8
VHL	0.04	0.009	-10000	0	0	27	27
ITGB3	0.033	0.017	-10000	0	0	120	120
NOS3	0.038	0.084	0.31	4	-0.38	7	11
VEGFR2 homodimer/VEGFA homodimer/Sck	0.031	0.055	-10000	0	-0.35	4	4
RAC1	0.039	0.01	-10000	0	0	35	35
PRKCA	-0.007	0.066	0.18	28	-0.36	4	32
PRKCB	-0.006	0.061	0.18	27	-0.36	4	31
VCL	0.039	0.01	-10000	0	0	35	35
VEGFA165/NRP1	0.011	0.055	0.17	21	-0.35	4	25
VEGFR1/2 heterodimer/VEGFA homodimer	0.033	0.057	-10000	0	-0.3	6	6
VEGFA165/NRP2	0.016	0.045	-10000	0	-0.12	54	54
MAPKKK cascade	-0.022	0.07	0.2	23	-0.35	6	29
NRP2	0.035	0.016	-10000	0	0	94	94
VEGFC homodimer	0.036	0.015	-10000	0	0	78	78
NCK1	0.036	0.014	-10000	0	0	77	77
ROCK1	0.04	0.007	-10000	0	0	18	18
FAK1/Paxillin	0.016	0.13	0.28	9	-0.32	30	39
MAP3K13	0.015	0.062	0.2	21	-0.3	6	27
PDPK1	-0.003	0.067	0.24	1	-0.28	7	8

×

Nephrin/Neph1 signaling in the kidney podocyte

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
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	1	-0.037	2	3
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.049	0.045	-10000	0	-0.15	18	18
PLCG1	0.039	0.011	-10000	0	0	39	39
ARRB2	0.039	0.01	-10000	0	0	37	37
WASL	0.04	0.008	-10000	0	0	23	23
Nephrin/NEPH1/podocin/CD2AP	0.073	0.071	0.21	1	-0.12	39	40
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.031	0.057	-10000	0	-0.14	30	30
FYN	0.002	0.063	0.17	58	-0.13	17	75
mol:Ca2+	0.076	0.063	0.2	1	-0.13	24	25
mol:DAG	0.077	0.064	0.21	1	-0.13	24	25
NPHS2	0.042	0.02	-10000	0	-0.043	19	19
mol:IP3	0.077	0.064	0.21	1	-0.13	24	25
regulation of endocytosis	0.054	0.058	-10000	0	-0.12	20	20
Nephrin/NEPH1/podocin/Cholesterol	0.063	0.048	0.17	3	-0.11	18	21
establishment of cell polarity	0.049	0.045	-10000	0	-0.15	18	18
Nephrin/NEPH1/podocin/NCK1-2	0.085	0.078	-10000	0	-0.11	38	38
Nephrin/NEPH1/beta Arrestin2	0.057	0.06	-10000	0	-0.12	20	20
NPHS1	0.04	0.022	0.086	7	-0.044	17	24
Nephrin/NEPH1/podocin	0.055	0.056	0.22	1	-0.12	19	20
TJP1	0.037	0.013	-10000	0	0	65	65
NCK1	0.036	0.014	-10000	0	0	77	77
NCK2	0.041	0.006	-10000	0	0	10	10
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.079	0.065	0.21	1	-0.13	24	25
CD2AP	0.037	0.013	-10000	0	0	63	63
Nephrin/NEPH1/podocin/GRB2	0.085	0.058	0.21	1	-0.12	18	19
GRB2	0.041	0.007	-10000	0	0	14	14
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.005	0.071	0.17	69	-0.12	3	72
cytoskeleton organization	0.013	0.053	0.25	4	-0.16	15	19
Nephrin/NEPH1	0.042	0.034	-10000	0	-0.096	18	18
Nephrin/NEPH1/ZO-1	0.054	0.062	-10000	0	-0.13	36	36

×

Sphingosine 1-phosphate (S1P) 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	0.04	0.008	-10000	0	0	23	23
SPHK1	0.041	0.007	-10000	0	0	16	16
GNAI2	0.041	0.006	-10000	0	0	13	13
mol:S1P	0.015	0.028	-10000	0	-0.17	11	11
GNAO1	0.034	0.016	-10000	0	0	101	101
mol:Sphinganine-1-P	-0.019	0.005	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.051	0.046	-10000	0	-0.16	12	12
GNAI3	0.038	0.012	-10000	0	0	46	46
G12/G13	0.053	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	0.007	-10000	0	0	15	15
S1P1/S1P	0.037	0.04	-10000	0	-0.15	11	11
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.035	0.016	-10000	0	0	94	94
S1P/S1P5/G12	0.032	0.036	-10000	0	-0.14	11	11
S1P/S1P3/Gq	0.015	0.078	0.17	1	-0.26	36	37
S1P/S1P4/Gi	-0.008	0.085	-10000	0	-0.2	66	66
GNAQ	0.038	0.012	-10000	0	0	50	50
GNAZ	0.039	0.011	-10000	0	0	38	38
GNA14	0.039	0.01	-10000	0	0	33	33
GNA15	0.037	0.014	-10000	0	0	69	69
GNA12	0.039	0.01	-10000	0	0	36	36
GNA13	0.04	0.009	-10000	0	0	28	28
GNA11	0.037	0.013	-10000	0	0	63	63
ABCC1	0.04	0.009	-10000	0	0	24	24

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.021	0.075	-10000	0	-0.38	10	10
SMARCC2	0.04	0.009	-10000	0	0	24	24
SMARCC1	0.04	0.008	-10000	0	0	20	20
TBX21	0.04	0.059	0.41	1	-0.28	1	2
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	82	82
FKBP5	0.03	0.019	-10000	0	0	150	150
GR alpha/HSP90/FKBP51/HSP90	-0.035	0.074	0.18	1	-0.21	19	20
PRL	0.048	0.07	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.059	0.12	0.42	3	-0.35	1	4
RELA	0.013	0.097	-10000	0	-0.16	121	121
FGG	-0.055	0.11	0.35	4	-0.32	1	5
GR beta/TIF2	-0.034	0.08	0.3	1	-0.24	6	7
IFNG	0.047	0.11	-10000	0	-0.43	1	1
apoptosis	-0.052	0.17	-10000	0	-0.42	62	62
CREB1	0.048	0.009	-10000	0	-10000	0	0
histone acetylation	0.024	0.082	0.3	9	-0.37	7	16
BGLAP	0.045	0.082	-10000	0	-0.88	2	2
GR/PKAc	0.032	0.085	0.31	1	-0.16	21	22
NF kappa B1 p50/RelA	0.011	0.17	-10000	0	-0.3	112	112
SMARCD1	0.04	0.008	-10000	0	0	20	20
MDM2	-0.013	0.047	0.14	3	-0.24	7	10
GATA3	0.05	0.014	-10000	0	-10000	0	0
AKT1	0.035	0.016	0.17	2	-0.052	6	8
CSF2	0.014	0.055	-10000	0	-10000	0	0
GSK3B	0.037	0.016	-10000	0	-0.011	46	46
NR1I3	-0.041	0.16	-10000	0	-0.43	20	20
CSN2	-0.05	0.098	0.3	4	-0.31	1	5
BRG1/BAF155/BAF170/BAF60A	0.075	0.066	-10000	0	-0.13	32	32
NFATC1	0.043	0.017	-10000	0	-10000	0	0
POU2F1	0.045	0.01	-10000	0	-10000	0	0
CDKN1A	-0.038	0.12	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.004	-10000	0	-10000	0	0
SFN	0.035	0.015	-10000	0	0	84	84
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.025	0.081	-10000	0	-0.2	26	26
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.1	0.28	-10000	0	-0.71	89	89
JUN	0.042	0.099	0.35	10	-0.28	4	14
IL4	0.043	0.059	0.32	1	-0.3	1	2
CDK5R1	0.039	0.009	-10000	0	0	27	27
PRKACA	0.035	0.015	-10000	0	0	87	87
cortisol/GR alpha (monomer)/AP-1	-0.041	0.068	0.2	11	-0.21	31	42
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.018	0.081	0.2	1	-0.2	19	20
cortisol/GR alpha (monomer)	-0.072	0.13	0.44	4	-0.4	1	5
NCOA2	0.037	0.014	-10000	0	0	69	69
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.033	0.053	-10000	0	-0.12	30	30
AP-1/NFAT1-c-4	0.04	0.14	-10000	0	-0.37	20	20
AFP	0.032	0.095	-10000	0	-10000	0	0
SUV420H1	0.039	0.01	-10000	0	0	31	31
IRF1	-0.1	0.22	-10000	0	-0.6	76	76
TP53	0.037	0.028	-10000	0	-10000	0	0
PPP5C	0.04	0.009	-10000	0	0	27	27
KRT17	0.03	0.16	-10000	0	-0.69	13	13
KRT14	0.021	0.18	0.5	8	-1.1	12	20
TBP	0.044	0.028	-10000	0	-0.32	2	2
CREBBP	0.031	0.057	0.34	14	-10000	0	14
HDAC1	0.033	0.012	-10000	0	-0.059	2	2
HDAC2	0.037	0.011	-10000	0	-10000	0	0
AP-1	0.04	0.14	-10000	0	-0.37	21	21
MAPK14	0.036	0.016	-10000	0	-0.013	48	48
MAPK10	0.032	0.021	-10000	0	-0.03	32	32
MAPK11	0.029	0.021	-10000	0	-0.003	148	148
KRT5	-0.005	0.26	-10000	0	-0.83	44	44
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.04	0.012	-10000	0	-0.068	2	2
STAT1	0.022	0.064	-10000	0	-0.18	46	46
CGA	0.046	0.066	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.06	0.11	0.31	3	-0.36	34	37
MAPK3	0.036	0.019	-10000	0	-0.03	36	36
MAPK1	0.035	0.018	-10000	0	-0.01	65	65
ICAM1	-0.078	0.32	-10000	0	-0.77	92	92
NFKB1	0.006	0.11	-10000	0	-0.19	110	110
MAPK8	0.05	0.083	0.57	1	-0.26	3	4
MAPK9	0.035	0.018	-10000	0	-0.031	23	23
cortisol/GR alpha (dimer)	-0.054	0.18	-10000	0	-0.44	64	64
BAX	-0.046	0.12	-10000	0	-0.44	2	2
POMC	0.055	0.098	0.5	2	-10000	0	2
EP300	0.028	0.048	0.32	10	-10000	0	10
cortisol/GR alpha (dimer)/p53	-0.076	0.13	0.42	4	-10000	0	4
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.051	0.26	7	-0.22	7	14
SGK1	-0.022	0.11	0.32	12	-0.3	43	55
IL13	0.05	0.094	-10000	0	-0.41	2	2
IL6	0.012	0.16	-10000	0	-0.61	19	19
PRKACG	0.041	0.006	-10000	0	0	12	12
IL5	0.048	0.097	-10000	0	-10000	0	0
IL2	0.037	0.12	-10000	0	-0.49	7	7
CDK5	0.035	0.014	-10000	0	0	77	77
PRKACB	0.038	0.012	-10000	0	0	49	49
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.01	0.22	-10000	0	-0.79	34	34
CDK5R1/CDK5	0.045	0.04	-10000	0	-0.13	19	19
NF kappa B1 p50/RelA/PKAc	0.041	0.15	-10000	0	-0.22	89	89
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.38	4	-0.32	1	5
SMARCA4	0.035	0.016	-10000	0	0	91	91
chromatin remodeling	-0.03	0.093	0.28	4	-0.35	12	16
NF kappa B1 p50/RelA/Cbp	0.026	0.16	0.41	7	-0.25	101	108
JUN (dimer)	0.042	0.099	0.35	10	-0.28	4	14
YWHAH	0.038	0.012	-10000	0	0	54	54
VIPR1	0.041	0.058	0.4	1	-0.28	1	2
NR3C1	-0.047	0.094	0.33	2	-0.31	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	-0.052	0.17	-10000	0	-0.42	62	62
cortisol/GR alpha (dimer)/Src-1	-0.055	0.13	0.4	5	-0.35	1	6
PBX1	0.044	0.013	-10000	0	-10000	0	0
POU1F1	0.046	0.009	-10000	0	-10000	0	0
SELE	0.023	0.12	-10000	0	-0.4	4	4
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.03	0.093	0.28	4	-0.35	12	16
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.38	4	-0.32	1	5
mol:cortisol	-0.043	0.067	0.28	2	-10000	0	2
MMP1	0.013	0.17	-10000	0	-0.78	19	19

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.047	0.045	-9999	-0.14	27	27
FBXW11	0.04	0.008	-9999	0	23	23
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.04	0.008	-9999	0	23	23
CHUK	0.038	0.012	-9999	0	52	52
NF kappa B2 p100/RelB	0.095	0.066	-9999	-0.12	29	29
NFKB1	0.035	0.015	-9999	0	85	85
MAP3K14	0.04	0.009	-9999	0	27	27
NF kappa B1 p50/RelB	0.042	0.05	-9999	-0.14	34	34
RELB	0.04	0.009	-9999	0	25	25
NFKB2	0.04	0.008	-9999	0	23	23
NF kappa B2 p52/RelB	0.051	0.021	-9999	-0.14	3	3
regulation of B cell activation	0.05	0.021	-9999	-0.14	3	3

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.037	0.015	-9999	-10000	0	0
SVIL	0.037	0.015	-9999	-10000	0	0
ZNF318	0.037	0.009	-9999	-0.035	2	2
JMJD2C	0.042	0.016	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.037	0.061	-9999	-0.11	67	67
CARM1	0.037	0.014	-9999	0	70	70
PRDX1	0.039	0.01	-9999	0	36	36
PELP1	0.039	0.009	-9999	0	29	29
CTNNB1	0.04	0.01	-9999	-10000	0	0
AKT1	0.038	0.01	-9999	0	38	38
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	0.04	0.01	-9999	-10000	0	0
GSN	0.04	0.011	-9999	-10000	0	0
NCOA2	0.037	0.014	-9999	0	69	69
NCOA6	0.04	0.011	-9999	-10000	0	0
DNA-PK	0.051	0.066	-9999	-0.14	45	45
NCOA4	0.04	0.009	-9999	0	24	24
PIAS3	0.041	0.009	-9999	-10000	0	0
cell proliferation	0.018	0.048	-9999	-0.42	6	6
XRCC5	0.038	0.01	-9999	0	38	38
UBE3A	0.043	0.005	-9999	-10000	0	0
T-DHT/AR/SNURF	0.038	0.062	-9999	-0.11	76	76
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	128	128
TGFB1I1	0.042	0.007	-9999	-10000	0	0
T-DHT/AR/CyclinD1	0.013	0.078	-9999	-0.12	118	118
XRCC6	0.036	0.014	-9999	0	69	69
T-DHT/AR	0.036	0.057	-9999	-0.1	69	69
CTDSP1	0.041	0.006	-9999	-10000	0	0
CTDSP2	0.037	0.011	-9999	-10000	0	0
BRCA1	0.035	0.016	-9999	-10000	0	0
TCF4	0.036	0.013	-9999	0	59	59
CDKN2A	0.028	0.019	-9999	0	176	176
SRF	0.043	0.021	-9999	-0.14	4	4
NKX3-1	0.014	0.082	-9999	-0.3	28	28
KLK3	0.003	0.049	-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	0.034	0.065	-9999	-0.11	86	86
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	16	16
PRKDC	0.038	0.011	-9999	0	44	44
PA2G4	0.039	0.008	-9999	0	24	24
UBE2I	0.04	0.009	-9999	0	26	26
T-DHT/AR/Cyclin D3/CDK11 p58	0.035	0.057	-9999	-0.095	77	77
RPS6KA3	0.038	0.014	-9999	-10000	0	0
T-DHT/AR/ARA70	0.035	0.065	-9999	-0.11	86	86
LATS2	0.039	0.009	-9999	0	25	25
T-DHT/AR/PRX1	0.032	0.059	-9999	-0.098	79	79
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	0.064	-9999	-0.3	16	16
CASP8	0.039	0.009	-9999	0	28	28
T-DHT/AR/TIF2/CARM1	0.045	0.071	-9999	-0.11	67	67
TMPRSS2	0.013	0.091	-9999	-0.31	35	35
CCND1	0.031	0.019	-9999	-10000	0	0
PIAS1	0.041	0.01	-9999	-10000	0	0
mol:T-DHT	0.005	0.005	-9999	-10000	0	0
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	118	118
CMTM2	0.036	0.014	-9999	0	75	75
SNURF	0.041	0.006	-9999	0	10	10
ZMIZ1	0.005	0.005	-9999	-10000	0	0
CCND3	0.039	0.01	-9999	0	33	33
TGIF1	-0.001	0	-9999	-10000	0	0
FKBP4	0.037	0.015	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.02	0.023	0.22	2	-0.093	3	5
NFATC2	0.021	0.023	0.23	2	-0.11	3	5
NFATC3	0.021	0.023	0.21	2	-0.093	3	5
CD40LG	0.032	0.1	0.29	22	-0.23	2	24
PTGS2	0.013	0.091	0.31	12	-0.28	6	18
JUNB	0.03	0.019	-10000	0	0	162	162
CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.017	-10000	0	-0.1	4	4
CaM/Ca2+	0.032	0.017	-10000	0	-0.1	4	4
CALM1	0.041	0.011	-10000	0	-0.001	31	31
JUN	0.038	0.016	0.098	1	0	81	82
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.027	0.011	-10000	0	-0.1	2	2
FOSL1	0.041	0.007	-10000	0	0	15	15
CREM	0.04	0.008	-10000	0	0	22	22
Jun/NFAT1-c-4/p21SNFT	0.055	0.069	0.24	8	-0.16	2	10
FOS	0.028	0.022	0.098	1	0	205	206
IFNG	0.022	0.095	0.31	13	-0.24	1	14
AP-1/NFAT1-c-4	0.084	0.12	0.34	1	-0.23	4	5
FASLG	0.029	0.1	0.29	20	-0.24	3	23
NFAT1-c-4/ICER1	0.053	0.057	0.21	8	-0.14	2	10
IL2RA	0.028	0.1	0.32	16	-0.25	2	18
FKBP12/FK506	0.028	0.012	-10000	0	-0.13	2	2
CSF2	0.031	0.1	0.29	20	-0.23	2	22
JunB/Fra1/NFAT1-c-4	0.047	0.074	0.23	6	-0.16	5	11
IL4	0.03	0.1	0.29	20	-0.23	2	22
IL2	-0.042	0.24	-10000	0	-0.86	42	42
IL3	0.028	0.12	-10000	0	-0.58	19	19
FKBP1A	0.039	0.011	-10000	0	0	39	39
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.045	0.01	-10000	0	-10000	0	0

×

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	61	61
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.003	0.1	0.4	13	-10000	0	13
IL27/IL27R/JAK1	0.079	0.11	-10000	0	-0.89	2	2
TBX21	0.006	0.1	0.35	5	-0.56	2	7
IL12B	0.042	0.008	-10000	0	0	20	20
IL12A	-0.006	0.006	0.012	25	-10000	0	25
IL6ST	0.036	0.018	-10000	0	-0.031	1	1
IL27RA/JAK1	0.051	0.099	-10000	0	-1	2	2
IL27	0.043	0.009	-10000	0	-0.037	2	2
TYK2	0.039	0.016	-10000	0	-0.038	2	2
T-helper cell lineage commitment	0.007	0.062	0.2	23	-0.18	29	52
T-helper 2 cell differentiation	-0.003	0.1	0.4	13	-10000	0	13
T cell proliferation during immune response	-0.003	0.1	0.4	13	-10000	0	13
MAPKKK cascade	0.003	0.1	-10000	0	-0.4	13	13
STAT3	0.038	0.012	-10000	0	0	52	52
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	0.003	0.099	0.28	2	-0.52	2	4
IL27/IL27R/JAK2/TYK2	0.003	0.1	-10000	0	-0.41	13	13
positive regulation of T cell mediated cytotoxicity	0.003	0.1	-10000	0	-0.4	13	13
STAT1 (dimer)	0.06	0.13	-10000	0	-0.78	2	2
JAK2	0.035	0.019	-10000	0	-0.037	1	1
JAK1	0.039	0.01	-10000	0	0	36	36
STAT2 (dimer)	0.02	0.12	-10000	0	-0.4	16	16
T cell proliferation	0.004	0.1	0.34	1	-0.39	12	13
IL12/IL12R/TYK2/JAK2	0.012	0.17	-10000	0	-0.7	26	26
IL17A	0.009	0.057	0.2	21	-0.17	25	46
mast cell activation	-0.003	0.1	0.4	13	-10000	0	13
IFNG	0.013	0.03	0.096	3	-0.096	6	9
T cell differentiation	-0.001	0.003	0.014	1	-0.02	3	4
STAT3 (dimer)	0.025	0.12	-10000	0	-0.39	15	15
STAT5A (dimer)	0.024	0.12	-10000	0	-0.4	13	13
STAT4 (dimer)	0.024	0.12	-10000	0	-0.39	14	14
STAT4	0.04	0.009	-10000	0	0	28	28
T cell activation	-0.008	0.011	0.12	1	-0.046	31	32
IL27R/JAK2/TYK2	0.05	0.095	-10000	0	-0.93	2	2
GATA3	0.018	0.12	0.63	21	-10000	0	21
IL18	-0.006	0.006	0.002	178	-10000	0	178
positive regulation of mast cell cytokine production	0.024	0.12	-10000	0	-0.38	15	15
IL27/EBI3	0.058	0.023	-10000	0	-10000	0	0
IL27RA	0.024	0.1	-10000	0	-1.1	2	2
IL6	0.033	0.017	-10000	0	0	114	114
STAT5A	0.038	0.012	-10000	0	0	50	50
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.009	0.036	0.48	2	-10000	0	2
IL1B	-0.007	0.006	0.002	148	-10000	0	148
EBI3	0.039	0.015	-10000	0	-0.037	1	1
TNF	-0.008	0.005	0.006	63	-10000	0	63

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.033	0.054	-10000	0	-0.18	24	24
VEGFR1 homodimer/NRP1	0.008	0.047	-10000	0	-0.39	5	5
mol:DAG	-0.024	0.041	0.2	2	-0.31	6	8
VEGFR1 homodimer/NRP1/VEGFR 121	0.007	0.042	-10000	0	-0.36	5	5
CaM/Ca2+	0.026	0.053	0.2	2	-0.28	7	9
HIF1A	0.045	0.034	-10000	0	-0.28	5	5
GAB1	0.038	0.012	-10000	0	0	49	49
AKT1	0	0.09	0.23	6	-0.26	17	23
PLCG1	-0.024	0.041	0.2	2	-0.31	6	8
NOS3	0.025	0.07	0.29	4	-0.26	10	14
CBL	0.04	0.008	-10000	0	0	23	23
mol:NO	0.026	0.071	0.3	4	-0.26	10	14
FLT1	0.018	0.044	-10000	0	-0.49	4	4
PGF	0.04	0.009	-10000	0	0	25	25
VEGFR1 homodimer/NRP2/VEGFR121	0.017	0.062	-10000	0	-0.31	8	8
CALM1	0.04	0.009	-10000	0	0	30	30
PIK3CA	0.03	0.019	-10000	0	0	150	150
eNOS/Hsp90	0.02	0.068	0.28	4	-0.25	10	14
endothelial cell proliferation	-0.005	0.064	0.29	2	-0.3	10	12
mol:Ca2+	-0.024	0.041	0.2	2	-0.31	6	8
MAPK3	-0.03	0.053	0.17	10	-0.25	9	19
MAPK1	-0.029	0.051	0.18	7	-0.25	9	16
PIK3R1	0.034	0.016	-10000	0	0	106	106
PLGF homodimer	0.04	0.009	-10000	0	0	25	25
PRKACA	0.035	0.015	-10000	0	0	87	87
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	0.047	-10000	0	-0.39	5	5
platelet activating factor biosynthetic process	-0.03	0.054	0.32	1	-0.3	5	6
PI3K	0.039	0.081	-10000	0	-0.24	17	17
PRKCA	-0.021	0.047	0.21	5	-0.26	8	13
PRKCB	-0.022	0.037	0.18	2	-0.29	6	8
VEGFR1 homodimer/PLGF homodimer	0.034	0.055	-10000	0	-0.17	28	28
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.039	0.011	-10000	0	0	42	42
mol:IP3	-0.024	0.041	0.2	2	-0.31	6	8
RASA1	-0.021	0.046	0.2	3	-0.32	7	10
NRP2	0.035	0.016	-10000	0	0	94	94
VEGFR1 homodimer	0.018	0.044	-10000	0	-0.49	4	4
VEGFB homodimer	0.039	0.011	-10000	0	0	42	42
NCK1	0.036	0.014	-10000	0	0	77	77
eNOS/Caveolin-1	0.041	0.081	0.32	3	-0.26	10	13
PTPN11	0.04	0.009	-10000	0	0	29	29
mol:PI-3-4-5-P3	0.037	0.079	-10000	0	-0.24	17	17
mol:L-citrulline	0.026	0.071	0.3	4	-0.26	10	14
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.066	-10000	0	-0.27	10	10
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.023	0.058	-10000	0	-0.28	10	10
CD2AP	0.037	0.013	-10000	0	0	63	63
PI3K/GAB1	0.044	0.088	-10000	0	-0.24	17	17
PDPK1	0	0.091	0.17	88	-0.26	12	100
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.027	0.056	-10000	0	-0.28	10	10
mol:NADP	0.026	0.071	0.3	4	-0.26	10	14
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.065	-10000	0	-0.26	10	10
VEGFR1 homodimer/NRP2	0.027	0.058	-10000	0	-0.18	28	28

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.09	0.049	-10000	0	-0.11	20	20
HDAC3	0.041	0.006	-10000	0	0	12	12
Ran/GTP/Exportin 1/HDAC4	-0.027	0.024	-10000	0	-0.12	33	33
GATA1/HDAC4	0.06	0.011	-10000	0	-10000	0	0
GATA1/HDAC5	0.059	0.014	-10000	0	-10000	0	0
GATA2/HDAC5	0.055	0.02	-10000	0	-10000	0	0
HDAC5/BCL6/BCoR	0.052	0.057	-10000	0	-0.12	33	33
HDAC9	0.035	0.016	-10000	0	0	92	92
Glucocorticoid receptor/Hsp90/HDAC6	0.044	0.039	-10000	0	-0.11	30	30
HDAC4/ANKRA2	0.049	0.033	-10000	0	-0.14	9	9
HDAC5/YWHAB	0.052	0.029	-10000	0	-0.14	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
GATA2	0.039	0.01	-10000	0	0	34	34
HDAC4/RFXANK	0.047	0.04	-10000	0	-0.14	19	19
BCOR	0.041	0.005	-10000	0	0	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.032	0.018	-10000	0	0	131	131
HDAC5	0.04	0.009	-10000	0	0	30	30
GNB1/GNG2	0.053	0.038	-10000	0	-0.14	19	19
Histones	-0.006	0.07	-10000	0	-0.2	32	32
ADRBK1	0.041	0.005	-10000	0	0	7	7
HDAC4	0.041	0.007	-10000	0	0	17	17
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	0.053	0.029	-10000	0	-0.14	7	7
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.041	0.007	-10000	0	0	15	15
HDAC5/RFXANK	0.046	0.041	-10000	0	-0.14	20	20
CAMK4	0.037	0.013	-10000	0	0	65	65
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	0.011	-10000	0	0	44	44
GATA1	0.042	0.002	-10000	0	0	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.038	0.012	-10000	0	0	50	50
NR3C1	0.038	0.011	-10000	0	0	44	44
SUMO1/HDAC4	0.04	0.061	-10000	0	-0.18	15	15
SRF	0.039	0.011	-10000	0	0	40	40
HDAC4/YWHAB	0.054	0.028	-10000	0	-0.14	7	7
Tubulin	0.028	0.009	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.053	0.029	-10000	0	-0.14	7	7
GNB1	0.041	0.005	-10000	0	0	7	7
RANGAP1	0.038	0.013	-10000	0	0	55	55
BCL6/BCoR	0.037	0.052	-10000	0	-0.14	33	33
HDAC4/HDAC3/SMRT (N-CoR2)	0.075	0.03	-10000	0	-0.12	5	5
HDAC4/SRF	0.068	0.035	-10000	0	-0.12	1	1
HDAC4/ER alpha	0.04	0.054	-10000	0	-0.14	41	41
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.006	0.07	-10000	0	-0.2	32	32
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	26	26
HDAC7/HDAC3	0.03	0.01	-10000	0	-0.13	2	2
BCL6	0.031	0.018	-10000	0	0	141	141
HDAC4/CaMK II delta B	0.04	0.007	-10000	0	0	17	17
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	0.07	0.18	1	-0.18	33	34
NPC	0.02	0.022	-10000	0	-0.085	23	23
MEF2C	0.036	0.014	-10000	0	0	77	77
RAN	0.041	0.006	-10000	0	0	11	11
HDAC4/MEF2C	0.094	0.062	-10000	0	-0.12	16	16
GNG2	0.039	0.01	-10000	0	0	34	34
NCOR2	0.04	0.009	-10000	0	0	26	26
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	86	86
RFXANK	0.036	0.014	-10000	0	0	77	77
nuclear import	-0.037	0.04	0.18	13	-10000	0	13

×

Insulin Pathway

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
CBL/APS/CAP	0.06	0.04	-10000	0	-0.11	10	10
TC10/GTP	0.05	0.037	-10000	0	-0.1	11	11
Insulin Receptor/Insulin/IRS1/Shp2	0.087	0.058	-10000	0	-0.12	22	22
HRAS	0.04	0.009	-10000	0	0	29	29
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.038	0.012	-10000	0	0	54	54
FOXO3	-0.005	0.009	0.02	7	-0.038	5	12
AKT1	0.015	0.098	0.24	32	-10000	0	32
INSR	0.041	0.015	0.082	8	-10000	0	8
Insulin Receptor/Insulin	0.083	0.052	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	39	39
CRK	0.038	0.011	-10000	0	0	45	45
PTPN1	-0.006	0.041	0.15	32	-10000	0	32
CAV1	-0.008	0.041	0.17	16	-10000	0	16
CBL/APS/CAP/Crk-II/C3G	0.081	0.042	-10000	0	-0.11	6	6
Insulin Receptor/Insulin/IRS1/NCK2	0.093	0.047	-10000	0	-0.11	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.04	0.065	-10000	0	-0.11	41	41
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.023	0.096	-10000	0	-0.31	34	34
RPS6KB1	0.004	0.09	0.21	36	-0.18	9	45
PARD6A	0.036	0.015	-10000	0	0	80	80
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	0.082	-10000	0	-0.69	7	7
PIK3R1	0.034	0.016	-10000	0	0	106	106
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.049	0.083	0.22	18	-0.18	13	31
HRAS/GTP	-0.027	0.032	-10000	0	-0.15	2	2
Insulin Receptor	0.041	0.015	0.081	8	-10000	0	8
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.1	0.06	-10000	0	-0.11	10	10
PRKCI	-0.007	0.13	-10000	0	-0.38	54	54
Insulin Receptor/Insulin/GRB14/PDK1	0.019	0.053	-10000	0	-0.12	42	42
SHC1	0.04	0.009	-10000	0	0	29	29
negative regulation of MAPKKK cascade	0.046	0.085	-10000	0	-0.56	7	7
PI3K	0.05	0.073	-10000	0	-0.12	41	41
NCK2	0.041	0.006	-10000	0	0	10	10
RHOQ	0.039	0.01	-10000	0	0	35	35
mol:H2O2	-0.002	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
AKT2	0.014	0.095	0.22	30	-10000	0	30
PRKCZ	0.036	0.09	-10000	0	-0.33	22	22
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.009	0.039	0.16	15	-10000	0	15
F2RL2	0.036	0.014	-10000	0	0	76	76
TRIP10	0.038	0.012	-10000	0	0	48	48
Insulin Receptor/Insulin/Shc	0.069	0.037	-10000	0	-0.098	5	5
TC10/GTP/CIP4/Exocyst	0.046	0.029	-10000	0	-0.11	12	12
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.092	0.071	-10000	0	-0.12	22	22
RAPGEF1	0.04	0.008	-10000	0	0	22	22
RASA1	0.036	0.014	-10000	0	0	73	73
NCK1	0.036	0.014	-10000	0	0	77	77
CBL/APS/CAP/Crk-II	0.066	0.035	-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	0.052	-10000	0	-0.11	11	11
INPP5D	-0.013	0.019	0.048	18	-0.094	7	25
SOS1	0.038	0.013	-10000	0	0	57	57
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	29	29
IRS1	0.04	0.008	-10000	0	0	22	22
p62DOK/RasGAP	0.046	0.086	-10000	0	-0.56	7	7
INS	0.044	0.013	0.083	13	-10000	0	13
mol:PI-3-4-P2	-0.013	0.018	0.048	18	-0.093	7	25
GRB2	0.041	0.007	-10000	0	0	14	14
EIF4EBP1	0.003	0.081	0.19	30	-0.17	3	33
PTPRA	0.042	0.013	0.082	5	0	34	39
PIK3CA	0.03	0.019	-10000	0	0	150	150
TC10/GTP/CIP4	0.046	0.029	-10000	0	-0.11	12	12
PDPK1	0.04	0.009	-10000	0	0	27	27
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.027	0.059	-10000	0	-0.19	10	10
Insulin Receptor/Insulin/IRS1	0.07	0.037	-10000	0	-0.099	8	8
Insulin Receptor/Insulin/IRS3	0.058	0.03	-10000	0	-0.14	3	3
Par3/Par6	0.066	0.051	-10000	0	-0.1	14	14

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.015	0.17	-10000	0	-0.7	13	13
NCK1/PAK1/Dok-R	-0.031	0.073	-10000	0	-0.34	14	14
NCK1/Dok-R	0.049	0.099	-10000	0	-0.87	2	2
PIK3CA	0.03	0.018	-10000	0	0	150	150
mol:beta2-estradiol	-0.009	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	29	29
Rac/GDP	0.029	0.01	-10000	0	-0.13	1	1
F2	0.01	0.038	-10000	0	-0.083	1	1
TNIP2	0.038	0.012	-10000	0	0	48	48
NF kappa B/RelA	0.074	0.1	-10000	0	-0.84	2	2
FN1	0.021	0.021	-10000	0	0	273	273
PLD2	0.032	0.079	-10000	0	-0.9	2	2
PTPN11	0.04	0.009	-10000	0	0	29	29
GRB14	0.038	0.012	-10000	0	0	54	54
ELK1	0.032	0.08	-10000	0	-0.84	2	2
GRB7	0.037	0.013	-10000	0	0	62	62
PAK1	0.037	0.014	-10000	0	0	66	66
Tie2/Ang1/alpha5/beta1 Integrin	0.036	0.12	-10000	0	-0.86	2	2
CDKN1A	0.013	0.19	-10000	0	-0.62	39	39
ITGA5	0.037	0.013	-10000	0	0	58	58
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.053	0.098	-10000	0	-0.87	2	2
CRK	0.038	0.011	-10000	0	0	45	45
mol:NO	0.029	0.15	-10000	0	-0.54	12	12
PLG	0.03	0.077	-10000	0	-0.9	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.026	0.14	-10000	0	-0.75	6	6
GRB2	0.041	0.007	-10000	0	0	14	14
PIK3R1	0.034	0.017	-10000	0	0	106	106
ANGPT2	-0.045	0.29	-10000	0	-1	38	38
BMX	0.031	0.079	-10000	0	-0.9	2	2
ANGPT1	0.03	0.057	-10000	0	-10000	0	0
tube development	-0.003	0.21	-10000	0	-0.7	39	39
ANGPT4	0.036	0.02	-10000	0	-0.015	68	68
response to hypoxia	0.001	0.008	0.037	2	-0.062	2	4
Tie2/Ang1/GRB14	0.053	0.091	-10000	0	-0.91	2	2
alpha5/beta1 Integrin	0.045	0.046	-10000	0	-0.14	28	28
FGF2	0.038	0.012	-10000	0	0	46	46
STAT5A (dimer)	0.013	0.24	-10000	0	-0.79	39	39
mol:L-citrulline	0.029	0.15	-10000	0	-0.54	12	12
AGTR1	0.032	0.025	-10000	0	-0.047	34	34
MAPK14	0.04	0.13	-10000	0	-1	4	4
Tie2/SHP2	0.036	0.11	-10000	0	-0.66	4	4
TEK	0.028	0.11	-10000	0	-0.69	4	4
RPS6KB1	0.015	0.16	-10000	0	-0.66	11	11
Angiotensin II/AT1	0.025	0.024	-10000	0	-0.056	34	34
Tie2/Ang1/GRB2	0.058	0.093	-10000	0	-0.91	2	2
MAPK3	0.027	0.077	-10000	0	-0.85	2	2
MAPK1	0.027	0.076	-10000	0	-0.85	2	2
Tie2/Ang1/GRB7	0.054	0.091	-10000	0	-0.91	2	2
NFKB1	0.035	0.015	-10000	0	0	85	85
MAPK8	0.031	0.081	-10000	0	-0.9	2	2
PI3K	0.017	0.16	-10000	0	-0.93	6	6
FES	0.043	0.11	-10000	0	-1	2	2
Crk/Dok-R	0.057	0.096	-10000	0	-0.87	2	2
Tie2/Ang1/ABIN2	0.055	0.092	-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	-0.63	13	13
STAT5A	0.038	0.012	-10000	0	0	50	50
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.061	0.18	-10000	0	-0.7	7	7
Tie2/Ang2	-0.014	0.27	-10000	0	-0.95	39	39
Tie2/Ang1	0.042	0.084	-10000	0	-0.94	2	2
FOXO1	0.015	0.19	-10000	0	-0.6	38	38
ELF1	0.047	0.019	-10000	0	-0.13	2	2
ELF2	0.039	0.08	-10000	0	-0.9	2	2
mol:Choline	0.032	0.078	-10000	0	-0.87	2	2
cell migration	-0.018	0.048	-10000	0	-0.19	14	14
FYN	-0.011	0.23	-10000	0	-0.8	39	39
DOK2	0.032	0.018	-10000	0	0	130	130
negative regulation of cell cycle	0.017	0.18	-10000	0	-0.56	39	39
ETS1	0.042	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	39	39
NOS3	0.025	0.16	-10000	0	-0.61	12	12
RAC1	0.039	0.01	-10000	0	0	35	35
TNF	0.049	0.014	-10000	0	-10000	0	0
MAPKKK cascade	0.032	0.078	-10000	0	-0.87	2	2
RASA1	0.036	0.014	-10000	0	0	73	73
Tie2/Ang1/Shc	0.058	0.093	-10000	0	-0.91	2	2
NCK1	0.036	0.014	-10000	0	0	77	77
vasculogenesis	0.03	0.14	0.36	2	-0.48	13	15
mol:Phosphatidic acid	0.032	0.078	-10000	0	-0.87	2	2
mol:Angiotensin II	0	0.008	-10000	0	-0.033	30	30
mol:NADP	0.029	0.15	-10000	0	-0.54	12	12
Rac1/GTP	0.027	0.15	-10000	0	-0.67	8	8
MMP2	0.032	0.088	-10000	0	-0.9	2	2

×

Arf1 pathway

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
coatomer protein complex	0.023	0.048	0.15	68	-10000	0	68
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.013	0.032	0.13	2	-0.12	7	9
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	-0.11	1	1
CLTB	0.04	0.009	-10000	0	0	25	25
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	128	128
CLTA	0.04	0.008	-10000	0	0	20	20
mol:GTP	-0.003	0.002	0.012	6	-0.02	1	7
ARFGAP1	-0.009	0.004	0	78	-10000	0	78
mol:PI-4-5-P2	0.01	0.016	0.079	25	-0.062	1	26
ARF1/GTP	0.023	0.012	0.079	1	-0.14	1	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.026	0.058	0.17	64	-0.17	4	68
mol:Choline	0.01	0.016	0.079	25	-0.06	1	26
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.038	0.012	-10000	0	0	51	51
DDEF1	0.005	0.012	0.08	12	-10000	0	12
ARF1/GDP	0.006	0.011	-10000	0	-0.077	4	4
AP2M1	0.032	0.018	-10000	0	0	135	135
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.01	0.016	0.049	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	0.018	-10000	0	-0.04	24	24
COPA	0.04	0.009	-10000	0	0	26	26
RAC1	0.039	0.01	-10000	0	0	35	35
ARF1/GTP/coatomer protein complex	0.013	0.039	0.14	1	-0.19	11	12
ARF1/GTP/ARHGAP10	0.024	0.01	-10000	0	-0.11	1	1
GGA3	0.04	0.007	-10000	0	0	18	18
ARF1/GTP/Membrin	0.023	0.048	-10000	0	-0.22	19	19
AP2A1	0.039	0.011	-10000	0	0	41	41
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.034	-10000	0	-0.17	13	13
ARF1/GDP/Membrin	0.025	0.055	-10000	0	-0.25	19	19
Arfaptin 2/Rac/GDP	0.05	0.019	-10000	0	-0.11	1	1
CYTH2	-0.003	0.002	0.012	6	-0.02	1	7
ARF1/GTP/GGA3	0.048	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	0.007	0.057	-10000	0	-0.34	7	7
PLD2	0.01	0.016	0.08	25	-0.06	1	26
ARF-GAP1/v-SNARE	-0.009	0.004	0	78	-10000	0	78
PIP5K1A	0.01	0.016	0.079	25	-0.063	1	26
ARF1/GTP/Membrin/GBF1/p115	0.018	0.025	-10000	0	-0.075	18	18
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.01	0.016	0.079	25	-0.06	1	26
KDEL Receptor/Ligand/ARF-GAP1	-0.009	0.004	0	78	-10000	0	78
GOSR2	0.011	0.052	-10000	0	-0.31	14	14
USO1	0.004	0.008	0.04	25	-0.029	1	26
GBF1	0.004	0.073	-10000	0	-0.34	23	23
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	0.037	0.062	-10000	0	-0.13	40	40

×

Signaling events mediated by HDAC Class III

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
EP300	0.036	0.014	-10000	0	0	72	72
HDAC4	0.041	0.007	-10000	0	0	17	17
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	0.025	0.069	0.29	22	-10000	0	22
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.04	0.008	-10000	0	0	20	20
FOXO3	0.003	0.043	0.25	16	-10000	0	16
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.005	0.033	-10000	0	-0.18	17	17
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.037	0.014	-10000	0	0	69	69
TAT	0.036	0.014	-10000	0	0	72	72
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.01	0.002	-10000	0	-10000	0	0
PPARGC1A	0.038	0.013	-10000	0	0	55	55
FHL2	0.04	0.008	-10000	0	0	21	21
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	0.037	0.049	0.2	18	-0.21	6	24
SIRT1	0.037	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.072	0.033	-10000	0	-0.12	8	8
SIRT1/Histone H1b	0.006	0.088	-10000	0	-0.2	63	63
apoptosis	-0.064	0.045	0.14	15	-10000	0	15
SIRT1/PGC1A	0.045	0.026	-10000	0	-0.11	8	8
p53/SIRT1	-0.008	0.089	-10000	0	-0.15	157	157
SIRT1/FOXO4	0.01	0.074	-10000	0	-0.15	81	81
FOXO1/FHL2/SIRT1	0.045	0.025	-10000	0	-0.1	12	12
HIST1H1E	-0.003	0.068	-10000	0	-0.2	49	49
SIRT1/p300	0.044	0.043	-10000	0	-0.14	24	24
muscle cell differentiation	-0.018	0.024	0.11	9	-0.21	2	11
TP53	0.024	0.018	-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	49	49
MEF2D	0.04	0.009	-10000	0	0	24	24
HIV-1 Tat/SIRT1	0.048	0.03	-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

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.038	0.012	-10000	0	0	54	54
Ran/GTP/Exportin 1/HDAC4	-0.029	0.033	-10000	0	-0.16	24	24
MDM2/SUMO1	0.039	0.061	-10000	0	-0.19	15	15
HDAC4	0.041	0.007	-10000	0	0	17	17
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	0.032	-10000	0	-0.14	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0	0.04	-10000	0	-0.17	15	15
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.041	0.006	-10000	0	0	11	11
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.04	0.009	-10000	0	0	30	30
SUMO1/HDAC4	0.04	0.061	-10000	0	-0.18	15	15
SUMO1/HDAC1	0.037	0.064	-10000	0	-0.18	22	22
RANGAP1	0.038	0.013	-10000	0	0	55	55
MDM2/SUMO1/SUMO1	0.083	0.055	-10000	0	-0.13	18	18
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
Ran/GTP	0.023	0.057	0.17	1	-0.15	35	36
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	26	26
Ran/GTP/Exportin 1	0.019	0.067	0.2	13	-0.2	23	36
NPC	0.02	0.022	-10000	0	-0.085	23	23
PIAS2	0.038	0.012	-10000	0	0	52	52
PIAS1	0.04	0.009	-10000	0	0	28	28
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.037	0.018	-10000	0	-0.13	3	3
PDGFRB	0.037	0.014	-10000	0	0	64	64
SPHK1	0.016	0.068	-10000	0	-0.61	6	6
mol:S1P	0.013	0.063	-10000	0	-0.51	6	6
S1P1/S1P/Gi	0.021	0.087	-10000	0	-0.3	24	24
GNAO1	0.034	0.018	-10000	0	-0.002	108	108
PDGFB-D/PDGFRB/PLCgamma1	0.008	0.1	0.24	2	-0.27	32	34
PLCG1	0.006	0.089	0.2	5	-0.29	25	30
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	-0.015	22	22
GNAI3	0.038	0.015	-10000	0	-0.006	55	55
GNAI1	0.035	0.018	-10000	0	-0.002	101	101
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.027	0.026	0.2	8	-0.14	1	9
S1P1/S1P	0.022	0.058	-10000	0	-0.32	7	7
negative regulation of cAMP metabolic process	0.022	0.086	-10000	0	-0.3	24	24
MAPK3	0.008	0.1	-10000	0	-0.42	17	17
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.01	-10000	0	-0.13	1	1
RhoA/GDP	0.029	0.014	-10000	0	-0.13	4	4
KDR	0.043	0.011	-10000	0	-10000	0	0
PLCB2	0.017	0.057	-10000	0	-0.28	7	7
RAC1	0.039	0.01	-10000	0	0	35	35
RhoA/GTP	0.023	0.053	-10000	0	-0.28	7	7
receptor internalization	0.021	0.055	-10000	0	-0.3	7	7
PTGS2	-0.002	0.15	-10000	0	-0.81	11	11
Rac1/GTP	0.022	0.053	-10000	0	-0.28	7	7
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	0.086	-10000	0	-0.3	24	24
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.039	0.014	-10000	0	-0.006	47	47
MAPK1	0.009	0.1	-10000	0	-0.45	16	16
S1P1/S1P/PDGFB-D/PDGFRB	0.033	0.07	-10000	0	-0.26	8	8
ABCC1	0.04	0.009	-10000	0	0	24	24

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.063	0.036	-9999	0	-0.098	17	17
MAPK9	0.009	0.003	-9999	0	0	39	39
adrenocorticotropin secretion	-0.01	0.003	0	45	-10000	0	45
GNB1/GNG2	0.048	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	0.025	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	0.001	-9999	0	-10000	0	0
GNAL	0.04	0.009	-9999	0	0	27	27
GNG2	0.039	0.01	-9999	0	0	34	34
CRH	0.038	0.011	-9999	0	0	45	45
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.009	0.002	-9999	0	0	29	29
MAPK11	0.007	0.004	-9999	0	0	132	132

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.016	0.12	-10000	0	-0.85	9	9
MKNK1	0.04	0.009	-10000	0	0	25	25
MAPK14	0.041	0.054	0.17	1	-0.14	31	32
ATF2/c-Jun	-0.018	0.1	-10000	0	-0.31	43	43
MAPK11	0.032	0.054	-10000	0	-0.14	31	31
MITF	0.02	0.061	-10000	0	-0.29	15	15
MAPKAPK5	0.019	0.058	-10000	0	-0.27	16	16
KRT8	0.016	0.062	-10000	0	-0.23	25	25
MAPKAPK3	0.041	0.006	-10000	0	0	12	12
MAPKAPK2	0.04	0.008	-10000	0	0	21	21
p38alpha-beta/CK2	0.042	0.078	-10000	0	-0.31	14	14
CEBPB	0.022	0.053	-10000	0	-0.3	9	9
SLC9A1	0.021	0.056	-10000	0	-0.28	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.015	0.073	0.23	1	-0.24	26	27
p38alpha-beta/MNK1	0.054	0.077	-10000	0	-0.32	10	10
JUN	-0.021	0.1	-10000	0	-0.31	44	44
PPARGC1A	0.022	0.054	-10000	0	-0.28	12	12
USF1	0.019	0.058	-10000	0	-0.26	16	16
RAB5/GDP/GDI1	0.007	0.077	-10000	0	-0.19	29	29
NOS2	0.015	0.055	-10000	0	-0.28	14	14
DDIT3	0.017	0.061	-10000	0	-0.22	25	25
RAB5A	0.041	0.006	-10000	0	0	13	13
HSPB1	0.003	0.052	0.28	3	-0.23	16	19
p38alpha-beta/HBP1	0.046	0.084	-10000	0	-0.2	26	26
CREB1	-0.003	0.097	-10000	0	-0.3	18	18
RAB5/GDP	0.029	0.012	-10000	0	-0.13	3	3
EIF4E	-0.007	0.066	0.2	22	-0.3	9	31
RPS6KA4	0.021	0.056	-10000	0	-0.28	13	13
PLA2G4A	-0.009	0.062	0.23	10	-0.3	12	22
GDI1	0.018	0.061	-10000	0	-0.26	20	20
TP53	0.002	0.063	-10000	0	-0.36	12	12
RPS6KA5	0.019	0.059	-10000	0	-0.25	18	18
ESR1	0.008	0.075	-10000	0	-0.22	43	43
HBP1	0.038	0.012	-10000	0	0	50	50
MEF2C	0.015	0.068	-10000	0	-0.28	20	20
MEF2A	0.019	0.057	-10000	0	-0.26	16	16
EIF4EBP1	0.002	0.09	-10000	0	-0.29	17	17
KRT19	0.008	0.08	-10000	0	-0.23	44	44
ELK4	0.02	0.056	-10000	0	-0.28	14	14
ATF6	0.019	0.057	-10000	0	-0.26	16	16
ATF1	-0.002	0.096	-10000	0	-0.3	18	18
p38alpha-beta/MAPKAPK2	0.054	0.077	-10000	0	-0.24	16	16
p38alpha-beta/MAPKAPK3	0.056	0.076	-10000	0	-0.33	9	9

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.047	0.012	-10000	0	-0.085	3	3
NFATC2	0.046	0.18	0.38	13	-0.39	39	52
NFATC3	0.069	0.067	0.29	26	-0.26	2	28
CD40LG	0.081	0.15	0.49	5	-0.48	4	9
ITCH	0.024	0.051	0.2	6	-0.21	17	23
CBLB	0.02	0.061	0.2	7	-0.26	19	26
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.044	0.14	0.37	3	-0.51	8	11
JUNB	0.03	0.019	-10000	0	0	162	162
CaM/Ca2+/Calcineurin A alpha-beta B1	0.044	0.048	-10000	0	-0.18	21	21
T cell anergy	0.003	0.067	0.25	6	-0.28	17	23
TLE4	0.009	0.16	0.28	4	-0.41	50	54
Jun/NFAT1-c-4/p21SNFT	0.081	0.15	-10000	0	-0.46	3	3
AP-1/NFAT1-c-4	0.09	0.19	-10000	0	-0.54	2	2
IKZF1	0.022	0.11	0.22	19	-0.26	39	58
T-helper 2 cell differentiation	0.033	0.14	0.45	2	-0.46	4	6
AP-1/NFAT1	0.036	0.15	0.32	2	-0.25	43	45
CALM1	0.043	0.034	-10000	0	-0.11	22	22
EGR2	0.059	0.16	0.61	5	-1	2	7
EGR3	0.052	0.14	0.56	7	-0.51	2	9
NFAT1/FOXP3	0.058	0.14	0.33	3	-0.27	37	40
EGR1	0.028	0.021	-10000	0	-0.036	2	2
JUN	0.04	0.026	0.14	2	-0.041	16	18
EGR4	0.041	0.009	-10000	0	-0.036	2	2
mol:Ca2+	0.005	0.021	-10000	0	-0.099	21	21
GBP3	-0.02	0.21	0.3	9	-0.45	92	101
FOSL1	0.041	0.007	-10000	0	0	15	15
NFAT1-c-4/MAF/IRF4	0.094	0.15	-10000	0	-0.47	2	2
DGKA	0.026	0.13	0.29	9	-0.3	36	45
CREM	0.039	0.009	-10000	0	-0.002	23	23
NFAT1-c-4/PPARG	0.084	0.14	-10000	0	-0.5	2	2
CTLA4	0.025	0.1	0.23	1	-0.24	34	35
NFAT1-c-4 (dimer)/EGR1	0.062	0.15	-10000	0	-0.54	2	2
NFAT1-c-4 (dimer)/EGR4	0.09	0.15	-10000	0	-0.48	3	3
FOS	0.029	0.029	0.14	2	-0.039	15	17
IFNG	0.035	0.13	-10000	0	-0.49	6	6
T cell activation	0.05	0.12	0.52	2	-0.47	1	3
MAF	0.036	0.015	-10000	0	0	78	78
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.06	0.13	0.56	3	-0.51	22	25
TNF	0.046	0.13	0.46	2	-0.49	3	5
FASLG	0.049	0.17	0.69	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	0.025	0.12	0.27	2	-0.28	32	34
NFAT1-c-4/ICER1	0.084	0.15	-10000	0	-0.48	3	3
GATA3	0.041	0.012	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.038	0.13	-10000	0	-0.48	6	6
IL2RA	0.05	0.15	0.38	2	-0.46	10	12
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.021	0.12	0.27	3	-0.31	32	35
E2F1	0.032	0.05	-10000	0	-0.18	27	27
PPARG	0.039	0.01	-10000	0	0	34	34
SLC3A2	0.023	0.13	0.29	5	-0.31	37	42
IRF4	0.041	0.008	-10000	0	0	18	18
PTGS2	0.054	0.14	0.68	1	-0.5	4	5
CSF2	0.077	0.15	0.49	5	-0.48	4	9
JunB/Fra1/NFAT1-c-4	0.077	0.15	-10000	0	-0.48	2	2
IL4	0.033	0.14	0.45	2	-0.48	3	5
IL5	0.076	0.15	0.48	4	-0.48	4	8
IL2	0.05	0.12	0.52	2	-0.47	1	3
IL3	0.038	0.073	-10000	0	-0.4	11	11
RNF128	0.024	0.043	0.2	7	-0.15	21	28
NFATC1	0.061	0.13	0.51	22	-0.57	3	25
CDK4	-0.075	0.29	0.46	2	-1.2	28	30
PTPRK	0.01	0.15	0.26	6	-0.39	48	54
IL8	0.047	0.14	0.54	4	-0.46	5	9
POU2F1	0.046	0.01	-10000	0	-10000	0	0

×

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

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
MAP4K1	0.011	0.069	0.3	4	-0.36	4	8
CRKL	0.013	0.063	0.22	2	-0.37	4	6
HRAS	0.03	0.08	0.25	2	-0.28	10	12
mol:PIP3	0.025	0.088	0.28	3	-0.33	9	12
SPRED1	0.035	0.015	-10000	0	0	89	89
SPRED2	0.04	0.009	-10000	0	0	26	26
GAB1	0.018	0.061	-10000	0	-0.35	5	5
FOXO3	0.022	0.093	0.29	1	-0.36	15	16
AKT1	0.022	0.098	0.3	1	-0.39	15	16
BAD	0.018	0.094	0.28	1	-0.37	15	16
megakaryocyte differentiation	0.023	0.06	0.25	2	-0.31	3	5
GSK3B	0.023	0.1	0.32	9	-0.37	15	24
RAF1	0.022	0.075	0.25	8	-0.24	9	17
SHC1	0.04	0.009	-10000	0	0	29	29
STAT3	0.019	0.063	0.28	2	-0.35	5	7
STAT1	0.031	0.11	-10000	0	-0.77	4	4
HRAS/SPRED1	0.035	0.084	0.26	3	-0.27	8	11
cell proliferation	0.019	0.063	0.25	2	-0.37	4	6
PIK3CA	0.03	0.019	-10000	0	0	150	150
TEC	0.033	0.017	-10000	0	0	114	114
RPS6KB1	0.022	0.099	-10000	0	-0.38	12	12
HRAS/SPRED2	0.042	0.084	0.25	5	-0.25	9	14
LYN/TEC/p62DOK	0.042	0.098	-10000	0	-0.31	6	6
MAPK3	0.018	0.065	0.21	9	-0.24	6	15
STAP1	0.023	0.062	0.26	1	-0.34	5	6
GRAP2	0.038	0.013	-10000	0	0	55	55
JAK2	0.027	0.11	-10000	0	-0.62	5	5
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	0.063	0.093	0.3	1	-0.35	5	6
actin filament polymerization	0.024	0.063	0.26	1	-0.34	5	6
LYN	0.036	0.015	-10000	0	0	83	83
STAP1/STAT5A (dimer)	0.016	0.1	0.3	1	-0.46	7	8
PIK3R1	0.034	0.017	-10000	0	0	106	106
CBL/CRKL/GRB2	0.046	0.084	0.42	1	-0.37	4	5
PI3K	0.025	0.1	-10000	0	-0.34	15	15
PTEN	0.039	0.011	-10000	0	0	39	39
SCF/KIT/EPO/EPOR	0.059	0.13	-10000	0	-1.3	2	2
MAPK8	0.019	0.063	0.25	2	-0.38	4	6
STAT3 (dimer)	0.02	0.066	0.26	3	-0.34	5	8
positive regulation of transcription	0.018	0.058	0.19	11	-0.19	6	17
mol:GDP	0.039	0.086	0.27	1	-0.29	7	8
PIK3C2B	0.02	0.068	0.25	4	-0.35	5	9
CBL/CRKL	0.031	0.077	0.42	1	-0.37	4	5
FER	0.02	0.063	0.26	1	-0.35	5	6
SH2B3	0.023	0.062	0.26	1	-0.34	5	6
PDPK1	0.023	0.086	0.28	6	-0.3	9	15
SNAI2	0.024	0.067	0.25	3	-0.34	5	8
positive regulation of cell proliferation	0.02	0.11	0.34	1	-0.64	4	5
KITLG	0.043	0.015	-10000	0	-0.041	3	3
cell motility	0.02	0.11	0.34	1	-0.64	4	5
PTPN6	0.034	0.016	-10000	0	-0.005	74	74
EPOR	0.013	0.16	-10000	0	-0.62	15	15
STAT5A (dimer)	0.021	0.1	0.31	1	-0.48	7	8
SOCS1	0.038	0.012	-10000	0	0	52	52
cell migration	-0.018	0.062	0.38	4	-0.26	1	5
SOS1	0.038	0.013	-10000	0	0	57	57
EPO	0.043	0.011	-10000	0	-0.035	3	3
VAV1	0.037	0.014	-10000	0	0	67	67
GRB10	0.018	0.065	0.26	1	-0.35	5	6
PTPN11	0.037	0.011	-10000	0	-0.004	33	33
SCF/KIT	0.026	0.066	0.28	1	-0.36	5	6
GO:0007205	-0.002	0.004	-10000	0	-10000	0	0
MAP2K1	0.016	0.068	0.22	14	-0.22	5	19
CBL	0.04	0.008	-10000	0	0	23	23
KIT	0.018	0.16	-10000	0	-0.54	20	20
MAP2K2	0.014	0.063	0.22	8	-0.22	6	14
SHC/Grb2/SOS1	0.066	0.094	0.3	1	-0.33	5	6
STAT5A	0.023	0.1	0.31	1	-0.49	7	8
GRB2	0.041	0.007	-10000	0	0	14	14
response to radiation	0.026	0.07	0.25	4	-0.37	4	8
SHC/GRAP2	0.053	0.023	-10000	0	-0.14	1	1
PTPRO	0.021	0.056	0.25	2	-0.31	3	5
SH2B2	0.023	0.062	0.26	1	-0.34	5	6
DOK1	0.04	0.009	-10000	0	0	24	24
MATK	0.018	0.062	0.26	1	-0.38	4	5
CREBBP	0.059	0.029	0.14	4	-0.15	3	7
BCL2	-0.017	0.22	-10000	0	-0.6	52	52

×

Effects of Botulinum toxin

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
STX1A	-0.01	0.002	0	12	-10000	0	12
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.057	0.02	-10000	0	-0.14	2	2
STXBP1	0.039	0.011	-10000	0	0	39	39
ACh/CHRNA1	0.028	0.024	0.092	1	-0.05	29	30
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	16	16
mol:ACh	0.003	0.022	0.074	22	-0.086	4	26
RAB3GAP2	0.039	0.01	-10000	0	0	35	35
STX1A/SNAP25/VAMP2	0.057	0.055	0.18	1	-0.14	5	6
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.028	0.024	0.091	1	-0.05	29	30
UNC13B	0.04	0.009	-10000	0	0	25	25
CHRNA1	0.037	0.013	-10000	0	0	62	62
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.03	0.023	0.092	1	-0.051	27	28
SNAP25	0.006	0.002	-10000	0	0	57	57
VAMP2	0.005	0.002	-10000	0	0	62	62
SYT1	0.038	0.011	-10000	0	0	45	45
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	0.057	0.055	0.18	1	-0.14	5	6

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.04	0.009	-10000	0	0	26	26
CLTC	0.015	0.089	0.22	2	-0.45	12	14
calcium ion-dependent exocytosis	0.015	0.047	0.18	2	-0.2	8	10
Dynamin 2/GTP	0.021	0.041	-10000	0	-0.11	41	41
EXOC4	0.038	0.012	-10000	0	0	51	51
CD59	0.01	0.061	-10000	0	-0.35	11	11
CPE	0.011	0.013	-10000	0	-0.11	4	4
CTNNB1	0.039	0.01	-10000	0	0	32	32
membrane fusion	0.004	0.035	-10000	0	-0.2	5	5
CTNND1	-0.004	0.074	0.18	61	-0.2	3	64
DNM2	0.036	0.014	-10000	0	0	72	72
mol:PI-4-5-P2	0.017	0.056	0.18	4	-0.23	12	16
TSHR	0.014	0.015	-10000	0	-0.11	7	7
INS	0.004	0.1	-10000	0	-0.45	26	26
BIN1	0.041	0.007	-10000	0	0	17	17
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	0.04	0.007	-10000	0	0	18	18
mol:Ca2+	0.021	0.04	-10000	0	-0.11	41	41
JUP	0.009	0.064	-10000	0	-0.36	11	11
ASAP2/amphiphysin II	0.048	0.023	-10000	0	-0.098	11	11
ARF6/GTP	0.028	0.019	-10000	0	-0.13	8	8
CDH1	0.008	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	26	26
positive regulation of endocytosis	0.028	0.019	-10000	0	-0.13	8	8
EXOC2	0.041	0.006	-10000	0	0	12	12
substrate adhesion-dependent cell spreading	0.008	0.1	-10000	0	-0.37	27	27
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.039	0.011	-10000	0	0	40	40
regulation of calcium-dependent cell-cell adhesion	-0.035	0.086	0.36	12	-0.22	1	13
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	0.004	0.035	-10000	0	-0.17	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.014	0.061	-10000	0	-0.34	11	11
clathrin heavy chain/ACAP1	0.015	0.078	0.21	6	-0.37	11	17
JIP4/KLC1	0.044	0.031	-10000	0	-0.098	20	20
EXOC1	0.038	0.012	-10000	0	0	52	52
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	0.046	0.034	-10000	0	-0.11	20	20
receptor recycling	0.028	0.019	-10000	0	-0.13	8	8
CTNNA1	-0.005	0.072	0.18	57	-0.2	3	60
NME1	0.014	0.014	-10000	0	-0.11	5	5
clathrin coat assembly	0.014	0.089	0.22	2	-0.44	12	14
IL2RA	0.014	0.06	0.22	1	-0.33	10	11
VAMP3	0.015	0.015	-10000	0	-0.11	7	7
GLUT4/clathrin heavy chain/ACAP1	0.039	0.081	-10000	0	-0.35	11	11
EXOC6	0.038	0.013	-10000	0	0	56	56
PLD1	0.001	0.049	-10000	0	-0.2	28	28
PLD2	0.015	0.03	-10000	0	-0.19	5	5
EXOC5	0.04	0.009	-10000	0	0	26	26
PIP5K1C	0.012	0.049	0.16	3	-0.23	10	13
SDC1	0.011	0.061	-10000	0	-0.35	10	10
ARF6/GDP	0.026	0.039	-10000	0	-0.12	34	34
EXOC7	0.041	0.005	-10000	0	0	9	9
E-cadherin/beta catenin	0.038	0.09	0.23	1	-0.37	12	13
mol:Phosphatidic acid	0.004	0.035	-10000	0	-0.2	5	5
endocytosis	-0.046	0.023	0.098	11	-10000	0	11
SCAMP2	0.04	0.009	-10000	0	0	25	25
ADRB2	0.008	0.088	0.21	4	-0.4	14	18
EXOC3	0.041	0.005	-10000	0	0	7	7
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.027	0.044	0.19	4	-0.11	41	45
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.008	0.085	0.21	1	-0.41	13	14
RALA	0.04	0.009	-10000	0	0	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.02	0.092	-10000	0	-0.4	11	11

×

Aurora C signaling

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
INCENP	0.041	0.004	-9999	0	6	6
Aurora C/Aurora B/INCENP	0.064	0.045	-9999	-0.1	27	27
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	0.014	-9999	0	75	75
AURKC	0.042	0.002	-9999	0	1	1

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.04	0.009	-9999	0	25	25
GPC2	0.04	0.008	-9999	0	20	20
GPC2/Midkine	0.054	0.032	-9999	-0.14	13	13
neuron projection morphogenesis	0.054	0.032	-9999	-0.14	13	13

×

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	60	60
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	9	9
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	49	49
CNGB3	0.038	0.012	-10000	0	0	54	54
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	0.087	0.057	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0.024	0.008	-10000	0	-10000	0	0
Na + (4 Units)	0.065	0.03	-10000	0	-10000	0	0
GNAT2/GDP	0.079	0.039	-10000	0	-0.1	1	1
GNB5	0.04	0.009	-10000	0	0	28	28
mol:GMP (4 units)	-0.002	0.06	0.19	48	-10000	0	48
Cone Transducin	0.067	0.03	-10000	0	-0.1	1	1
SLC24A2	0.038	0.011	-10000	0	0	44	44
GNB3/GNGT2	0.053	0.023	-10000	0	-0.14	1	1
GNB3	0.037	0.013	-10000	0	0	63	63
GNAT2/GTP	0.03	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	0.05	0.018	-10000	0	-10000	0	0
mol:Pi	0.066	0.035	-10000	0	-0.12	1	1
Cone CNG Channel	0.078	0.046	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.038	0.011	-10000	0	0	44	44
RGS9	0.039	0.011	-10000	0	0	40	40
PDE6C	0.04	0.009	-10000	0	0	24	24
GNGT2	0.04	0.008	-10000	0	0	23	23
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.037	0.013	-10000	0	0	58	58

×

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	19	19
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	0.068	0.037	-10000	0	-0.11	2	2
mol:Na +	0.069	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	48	48
RDH5	0.037	0.014	-10000	0	0	68	68
SAG	0.041	0.006	-10000	0	0	11	11
mol:Ca2+	-0.018	0.081	0.33	20	-10000	0	20
Na + (4 Units)	0.056	0.038	-10000	0	-0.11	1	1
RGS9	0.039	0.011	-10000	0	0	40	40
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	32	32
GNGT1	0.04	0.009	-10000	0	0	28	28
GUCY2F	0.042	0.002	-10000	0	0	1	1
GNB5	0.04	0.009	-10000	0	0	28	28
mol:GMP (4 units)	0.04	0.025	0.17	14	-0.1	2	16
mol:11-cis-retinal	0.037	0.014	-10000	0	0	68	68
mol:cGMP	0.077	0.033	0.2	2	-0.11	1	3
GNB1	0.041	0.005	-10000	0	0	7	7
Rhodopsin	0.05	0.03	-10000	0	-0.14	7	7
SLC24A1	0.04	0.008	-10000	0	0	19	19
CNGA1	0.04	0.008	-10000	0	0	21	21
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	0.037	-10000	0	-0.11	1	1
RGS9BP	0.037	0.013	-10000	0	0	60	60
Metarhodopsin II/Transducin	0.024	0.019	-10000	0	-0.14	6	6
GCAP Family/Ca ++	0.073	0.024	-10000	0	-0.1	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	-0.1	5	5
PDE6B	0.041	0.004	-10000	0	0	6	6
PDE6A	0.04	0.007	-10000	0	0	18	18
PDE6G	0.038	0.013	-10000	0	0	57	57
RHO	0.04	0.008	-10000	0	0	23	23
PDE6	0.095	0.055	-10000	0	-0.15	2	2
GUCA1A	0.04	0.009	-10000	0	0	24	24
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