PARADIGM pathway analysis of mRNASeq expression data - Thyroid Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	246
Signaling events mediated by Stem cell factor receptor (c-Kit)	159
Signaling events regulated by Ret tyrosine kinase	144
TCGA08_retinoblastoma	139
Reelin signaling pathway	126
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	116
Noncanonical Wnt signaling pathway	108
Wnt signaling	104
FOXA2 and FOXA3 transcription factor networks	100
PDGFR-alpha signaling pathway	99

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Ephrin A reverse signaling	0.5104	246	1724	7	-0.52	0	1000	-1000	-0.027	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3299	159	12448	78	-0.8	0.24	1000	-1000	-0.076	-1000
Signaling events regulated by Ret tyrosine kinase	0.2988	144	11847	82	-0.46	0.013	1000	-1000	-0.084	-1000
TCGA08_retinoblastoma	0.2884	139	1114	8	-0.13	0.073	1000	-1000	-0.022	-1000
Reelin signaling pathway	0.2614	126	7111	56	-0.6	0.033	1000	-1000	-0.08	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2407	116	7901	68	-0.9	0.37	1000	-1000	-0.12	-1000
Noncanonical Wnt signaling pathway	0.2241	108	2818	26	-0.42	0.013	1000	-1000	-0.073	-1000
Wnt signaling	0.2158	104	730	7	-0.42	0.013	1000	-1000	-0.02	-1000
FOXA2 and FOXA3 transcription factor networks	0.2075	100	4637	46	-0.92	0.021	1000	-1000	-0.027	-1000
PDGFR-alpha signaling pathway	0.2054	99	4362	44	-0.51	0.033	1000	-1000	-0.057	-1000
IL4-mediated signaling events	0.1909	92	8446	91	-1.3	0.66	1000	-1000	-0.13	-1000
Signaling events mediated by the Hedgehog family	0.1763	85	4467	52	-0.38	0.2	1000	-1000	-0.077	-1000
Nongenotropic Androgen signaling	0.1701	82	4297	52	-0.34	0.16	1000	-1000	-0.06	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1598	77	4209	54	-0.6	0.028	1000	-1000	-0.093	-1000
Calcium signaling in the CD4+ TCR pathway	0.1577	76	2373	31	-0.53	0.013	1000	-1000	-0.081	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1473	71	2433	34	-0.17	0.013	1000	-1000	-0.065	-1000
Glypican 1 network	0.1307	63	3034	48	-0.38	0.028	1000	-1000	-0.049	-1000
Endothelins	0.1224	59	5754	96	-0.4	0.013	1000	-1000	-0.081	-1000
IGF1 pathway	0.1203	58	3311	57	-0.2	0.059	1000	-1000	-0.088	-1000
Glucocorticoid receptor regulatory network	0.1183	57	6511	114	-0.57	0.37	1000	-1000	-0.067	-1000
Ephrin B reverse signaling	0.1162	56	2711	48	-0.31	0.19	1000	-1000	-0.071	-1000
IL23-mediated signaling events	0.1162	56	3368	60	-0.34	0.02	1000	-1000	-0.15	-1000
TCR signaling in naïve CD8+ T cells	0.1120	54	5027	93	-0.2	0.087	1000	-1000	-0.076	-1000
BMP receptor signaling	0.1079	52	4225	81	-0.58	0.026	1000	-1000	-0.082	-1000
Glypican 2 network	0.1058	51	205	4	-0.086	-0.01	1000	-1000	-0.034	-1000
Arf6 signaling events	0.0996	48	2997	62	-0.32	0.021	1000	-1000	-0.064	-1000
Coregulation of Androgen receptor activity	0.0975	47	3632	76	-0.77	0.061	1000	-1000	-0.061	-1000
Syndecan-1-mediated signaling events	0.0975	47	1626	34	-0.2	0.013	1000	-1000	-0.054	-1000
HIF-1-alpha transcription factor network	0.0975	47	3616	76	-0.57	0.042	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0913	44	3816	85	-0.31	0.15	1000	-1000	-0.088	-1000
Signaling mediated by p38-alpha and p38-beta	0.0809	39	1736	44	-0.23	0.013	1000	-1000	-0.051	-1000
IL12-mediated signaling events	0.0788	38	3322	87	-0.41	0.022	1000	-1000	-0.12	-1000
Hedgehog signaling events mediated by Gli proteins	0.0788	38	2508	65	-0.66	0.061	1000	-1000	-0.057	-1000
Syndecan-4-mediated signaling events	0.0788	38	2554	67	-0.24	0.016	1000	-1000	-0.091	-1000
IL6-mediated signaling events	0.0747	36	2769	75	-0.21	0.059	1000	-1000	-0.09	-1000
Ras signaling in the CD4+ TCR pathway	0.0685	33	574	17	-0.095	0.013	1000	-1000	-0.039	-1000
EGFR-dependent Endothelin signaling events	0.0664	32	679	21	-0.11	0.013	1000	-1000	-0.073	-1000
Thromboxane A2 receptor signaling	0.0643	31	3307	105	-0.21	0.032	1000	-1000	-0.072	-1000
Osteopontin-mediated events	0.0622	30	1162	38	-0.26	0.013	1000	-1000	-0.098	-1000
amb2 Integrin signaling	0.0602	29	2441	82	-0.24	0.013	1000	-1000	-0.082	-1000
TCGA08_p53	0.0602	29	206	7	-0.084	0.053	1000	-1000	-0.013	-1000
FAS signaling pathway (CD95)	0.0602	29	1407	47	-0.26	0.03	1000	-1000	-0.046	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0581	28	2384	85	-0.28	0.013	1000	-1000	-0.077	-1000
Plasma membrane estrogen receptor signaling	0.0560	27	2386	86	-0.18	0.02	1000	-1000	-0.08	-1000
Visual signal transduction: Rods	0.0560	27	1404	52	-0.2	0.016	1000	-1000	-0.074	-1000
Regulation of Androgen receptor activity	0.0560	27	1896	70	-0.48	0.034	1000	-1000	-0.074	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0539	26	1364	52	-0.28	0.054	1000	-1000	-0.062	-1000
Regulation of p38-alpha and p38-beta	0.0539	26	1412	54	-0.47	0.013	1000	-1000	-0.06	-1000
ErbB2/ErbB3 signaling events	0.0498	24	1568	65	-0.13	0.027	1000	-1000	-0.064	-1000
IL27-mediated signaling events	0.0498	24	1244	51	-0.17	0.064	1000	-1000	-0.091	-1000
LPA receptor mediated events	0.0498	24	2467	102	-0.26	0.031	1000	-1000	-0.089	-1000
JNK signaling in the CD4+ TCR pathway	0.0477	23	404	17	-0.1	0.02	1000	-1000	-0.065	-1000
BCR signaling pathway	0.0477	23	2313	99	-0.19	0.022	1000	-1000	-0.092	-1000
Syndecan-2-mediated signaling events	0.0436	21	1485	69	-0.22	0.038	1000	-1000	-0.056	-1000
Signaling events mediated by PTP1B	0.0436	21	1603	76	-0.25	0.021	1000	-1000	-0.079	-1000
p75(NTR)-mediated signaling	0.0436	21	2682	125	-0.36	0.065	1000	-1000	-0.091	-1000
Fc-epsilon receptor I signaling in mast cells	0.0394	19	1869	97	-0.21	0.031	1000	-1000	-0.081	-1000
Nectin adhesion pathway	0.0394	19	1198	63	-0.26	0.033	1000	-1000	-0.07	-1000
Integrins in angiogenesis	0.0394	19	1651	84	-0.24	0.034	1000	-1000	-0.094	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0394	19	1677	88	-0.32	0.028	1000	-1000	-0.11	-1000
FOXM1 transcription factor network	0.0394	19	969	51	-0.19	0.047	1000	-1000	-0.15	-1000
ErbB4 signaling events	0.0373	18	1248	69	-0.14	0.057	1000	-1000	-0.079	-1000
Visual signal transduction: Cones	0.0373	18	714	38	-0.092	0.013	1000	-1000	-0.057	-1000
Aurora C signaling	0.0373	18	130	7	-0.058	0	1000	-1000	-0.04	-1000
IL1-mediated signaling events	0.0373	18	1157	62	-0.12	0.067	1000	-1000	-0.091	-1000
Regulation of nuclear SMAD2/3 signaling	0.0353	17	2329	136	-0.34	0.066	1000	-1000	-0.072	-1000
Syndecan-3-mediated signaling events	0.0353	17	624	35	-0.16	0.013	1000	-1000	-0.062	-1000
TCGA08_rtk_signaling	0.0353	17	456	26	-0.25	0.024	1000	-1000	-0.022	-1000
Aurora B signaling	0.0353	17	1180	67	-0.38	0.014	1000	-1000	-0.068	-1000
Insulin-mediated glucose transport	0.0332	16	513	32	-0.21	0.042	1000	-1000	-0.065	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0332	16	1972	120	-0.31	0.042	1000	-1000	-0.078	-1000
Presenilin action in Notch and Wnt signaling	0.0311	15	923	61	-0.21	0.043	1000	-1000	-0.066	-1000
Effects of Botulinum toxin	0.0311	15	399	26	-0.16	0.019	1000	-1000	-0.055	-1000
Rapid glucocorticoid signaling	0.0311	15	318	20	-0.093	0.015	1000	-1000	-0.04	-1000
Signaling events mediated by PRL	0.0311	15	527	34	-0.11	0.013	1000	-1000	-0.039	-1000
LPA4-mediated signaling events	0.0290	14	178	12	-0.12	0.016	1000	-1000	-0.025	-1000
IFN-gamma pathway	0.0290	14	957	68	-0.11	0.041	1000	-1000	-0.089	-1000
IL2 signaling events mediated by STAT5	0.0290	14	328	22	-0.067	0.039	1000	-1000	-0.044	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0290	14	464	33	-0.16	0.035	1000	-1000	-0.066	-1000
Class IB PI3K non-lipid kinase events	0.0290	14	42	3	-0.004	-1000	1000	-1000	-0.011	-1000
Ceramide signaling pathway	0.0270	13	1004	76	-0.18	0.024	1000	-1000	-0.058	-1000
Signaling events mediated by HDAC Class III	0.0270	13	540	40	-0.35	0.024	1000	-1000	-0.043	-1000
IL2 signaling events mediated by PI3K	0.0270	13	759	58	-0.066	0.031	1000	-1000	-0.082	-1000
VEGFR1 specific signals	0.0270	13	775	56	-0.071	0.041	1000	-1000	-0.081	-1000
Insulin Pathway	0.0249	12	944	74	-0.082	0.038	1000	-1000	-0.096	-1000
a4b1 and a4b7 Integrin signaling	0.0228	11	59	5	-0.03	0.004	1000	-1000	-0.03	-1000
Cellular roles of Anthrax toxin	0.0228	11	429	39	-0.092	0.019	1000	-1000	-0.025	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0228	11	498	45	-0.092	0.039	1000	-1000	-0.083	-1000
Regulation of Telomerase	0.0228	11	1153	102	-0.29	0.053	1000	-1000	-0.1	-1000
mTOR signaling pathway	0.0207	10	543	53	-0.044	0.021	1000	-1000	-0.059	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0207	10	870	83	-0.21	0.052	1000	-1000	-0.072	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0207	10	802	74	-0.18	0.086	1000	-1000	-0.097	-1000
Caspase cascade in apoptosis	0.0187	9	682	74	-0.092	0.029	1000	-1000	-0.048	-1000
BARD1 signaling events	0.0187	9	548	57	-0.033	0.054	1000	-1000	-0.059	-1000
Retinoic acid receptors-mediated signaling	0.0187	9	560	58	-0.12	0.034	1000	-1000	-0.073	-1000
S1P3 pathway	0.0187	9	380	42	-0.18	0.049	1000	-1000	-0.062	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0166	8	249	28	-0.18	0.031	1000	-1000	-0.054	-1000
Class I PI3K signaling events mediated by Akt	0.0166	8	555	68	-0.21	0.052	1000	-1000	-0.061	-1000
ceramide signaling pathway	0.0166	8	410	49	-0.092	0.03	1000	-1000	-0.049	-1000
TRAIL signaling pathway	0.0145	7	375	48	-0.077	0.047	1000	-1000	-0.062	-1000
S1P1 pathway	0.0145	7	267	36	-0.038	0.032	1000	-1000	-0.063	-1000
Canonical Wnt signaling pathway	0.0145	7	361	51	-0.047	0.068	1000	-1000	-0.052	-1000
Class I PI3K signaling events	0.0145	7	512	73	-0.25	0.023	1000	-1000	-0.065	-1000
FoxO family signaling	0.0124	6	419	64	-0.21	0.16	1000	-1000	-0.061	-1000
Canonical NF-kappaB pathway	0.0104	5	216	39	-0.092	0.072	1000	-1000	-0.084	-1000
Circadian rhythm pathway	0.0104	5	127	22	-0.06	0.013	1000	-1000	-0.063	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0104	5	212	37	-0.031	0.04	1000	-1000	-0.055	-1000
S1P5 pathway	0.0104	5	98	17	-0.017	0.022	1000	-1000	-0.053	-1000
S1P4 pathway	0.0104	5	138	25	-0.017	0.032	1000	-1000	-0.048	-1000
EPO signaling pathway	0.0083	4	224	55	-0.037	0.062	1000	-1000	-0.1	-1000
Signaling events mediated by HDAC Class I	0.0083	4	498	104	-0.092	0.059	1000	-1000	-0.074	-1000
Atypical NF-kappaB pathway	0.0083	4	149	31	-0.039	0.047	1000	-1000	-0.055	-1000
PLK1 signaling events	0.0062	3	284	85	-0.042	0.033	1000	-1000	-0.047	-1000
HIF-2-alpha transcription factor network	0.0062	3	137	43	-0.2	0.21	1000	-1000	-0.08	-1000
Signaling mediated by p38-gamma and p38-delta	0.0062	3	48	15	0	0.032	1000	-1000	-0.031	-1000
Paxillin-dependent events mediated by a4b1	0.0062	3	126	36	-0.03	0.024	1000	-1000	-0.071	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0062	3	474	125	-0.034	0.087	1000	-1000	-0.11	-1000
PDGFR-beta signaling pathway	0.0062	3	347	97	-0.18	0.064	1000	-1000	-0.091	-1000
p38 MAPK signaling pathway	0.0062	3	144	44	-0.038	0.026	1000	-1000	-0.068	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0041	2	59	23	-0.037	0.049	1000	-1000	-0.067	-1000
Signaling events mediated by HDAC Class II	0.0041	2	177	75	-0.048	0.036	1000	-1000	-0.07	-1000
Aurora A signaling	0.0041	2	163	60	-0.048	0.038	1000	-1000	-0.057	-1000
Arf6 downstream pathway	0.0041	2	120	43	-0.18	0.094	1000	-1000	-0.042	-1000
E-cadherin signaling in keratinocytes	0.0041	2	121	43	-0.004	0.053	1000	-1000	-0.07	-1000
PLK2 and PLK4 events	0.0021	1	5	3	0.01	0.022	1000	-1000	-0.019	-1000
E-cadherin signaling in the nascent adherens junction	0.0021	1	104	76	-0.17	0.074	1000	-1000	-0.086	-1000
Arf6 trafficking events	0.0021	1	76	71	-0.021	0.046	1000	-1000	-0.072	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.058	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.048	-1000
Arf1 pathway	0.0000	0	22	54	-0.005	0.036	1000	-1000	-0.05	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.063	-1000
Total	NA	4007	217615	7203	-30	-990	131000	-131000	-8.9	-131000

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.43	0.31	-9999	-0.62	336	336
EFNA5	-0.12	0.3	-9999	-0.82	75	75
FYN	-0.38	0.3	-9999	-0.56	336	336
neuron projection morphogenesis	-0.43	0.31	-9999	-0.62	336	336
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.43	0.32	-9999	-0.62	336	336
EPHA5	-0.52	0.4	-9999	-0.82	305	305

×

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

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
MAP4K1	-0.21	0.22	-10000	0	-0.4	280	280
CRKL	-0.22	0.24	-10000	0	-0.42	273	273
HRAS	-0.19	0.22	-10000	0	-0.51	42	42
mol:PIP3	-0.22	0.22	-10000	0	-0.41	273	273
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.012	0.038	-10000	0	-0.82	1	1
GAB1	-0.24	0.25	-10000	0	-0.45	273	273
FOXO3	-0.19	0.22	-10000	0	-0.38	273	273
AKT1	-0.22	0.23	-10000	0	-0.42	273	273
BAD	-0.19	0.22	-10000	0	-0.38	273	273
megakaryocyte differentiation	-0.25	0.25	-10000	0	-0.45	281	281
GSK3B	-0.19	0.22	-10000	0	-0.38	273	273
RAF1	-0.15	0.18	-10000	0	-0.46	23	23
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.24	0.25	-10000	0	-0.45	273	273
STAT1	-0.59	0.59	-10000	0	-1.1	273	273
HRAS/SPRED1	-0.17	0.14	-10000	0	-0.45	25	25
cell proliferation	-0.24	0.25	-10000	0	-0.45	276	276
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.24	0.25	-10000	0	-0.45	273	273
HRAS/SPRED2	-0.17	0.15	-10000	0	-0.45	26	26
LYN/TEC/p62DOK	-0.23	0.21	-10000	0	-0.41	273	273
MAPK3	-0.094	0.13	-10000	0	-0.32	21	21
STAP1	-0.26	0.25	-10000	0	-0.47	273	273
GRAP2	-0.042	0.21	-10000	0	-0.78	34	34
JAK2	-0.51	0.45	-10000	0	-0.9	273	273
STAT1 (dimer)	-0.58	0.57	-10000	0	-1.1	273	273
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.24	0.21	-10000	0	-0.42	276	276
actin filament polymerization	-0.23	0.24	-10000	0	-0.44	273	273
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.35	0.34	-10000	0	-0.64	273	273
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.21	0.19	-10000	0	-0.37	263	263
PI3K	-0.22	0.24	-10000	0	-0.42	274	274
PTEN	0.012	0.038	-10000	0	-0.82	1	1
SCF/KIT/EPO/EPOR	-0.74	0.72	-10000	0	-1.4	273	273
MAPK8	-0.24	0.26	-10000	0	-0.46	276	276
STAT3 (dimer)	-0.23	0.24	-10000	0	-0.44	273	273
positive regulation of transcription	-0.075	0.11	-10000	0	-0.26	21	21
mol:GDP	-0.23	0.19	-10000	0	-0.55	42	42
PIK3C2B	-0.24	0.25	-10000	0	-0.45	273	273
CBL/CRKL	-0.2	0.22	-10000	0	-0.39	273	273
FER	-0.24	0.25	-10000	0	-0.45	274	274
SH2B3	-0.24	0.25	-10000	0	-0.45	273	273
PDPK1	-0.2	0.21	-10000	0	-0.37	274	274
SNAI2	-0.24	0.26	-10000	0	-0.46	274	274
positive regulation of cell proliferation	-0.41	0.42	-10000	0	-0.77	273	273
KITLG	-0.004	0.1	-10000	0	-0.86	7	7
cell motility	-0.41	0.42	-10000	0	-0.77	273	273
PTPN6	0.021	0.018	-10000	0	-10000	0	0
EPOR	-0.14	0.18	-10000	0	-0.67	2	2
STAT5A (dimer)	-0.34	0.35	-10000	0	-0.63	273	273
SOCS1	0.009	0.048	-10000	0	-0.42	5	5
cell migration	0.24	0.25	0.45	276	-10000	0	276
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.005	0.041	-10000	0	-0.33	7	7
VAV1	-0.013	0.1	-10000	0	-0.36	34	34
GRB10	-0.24	0.25	-10000	0	-0.45	273	273
PTPN11	0.02	0.039	-10000	0	-0.81	1	1
SCF/KIT	-0.26	0.26	-10000	0	-0.48	273	273
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.11	0.15	-10000	0	-0.35	21	21
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.8	0.75	-10000	0	-1.5	273	273
MAP2K2	-0.11	0.15	-10000	0	-0.35	21	21
SHC/Grb2/SOS1	-0.23	0.21	-10000	0	-0.41	273	273
STAT5A	-0.35	0.36	-10000	0	-0.66	273	273
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.24	0.25	-10000	0	-0.45	274	274
SHC/GRAP2	-0.042	0.16	-10000	0	-0.63	31	31
PTPRO	-0.25	0.25	-10000	0	-0.46	281	281
SH2B2	-0.24	0.25	-10000	0	-0.45	273	273
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.24	0.25	-10000	0	-0.46	276	276
CREBBP	0.018	0.021	-10000	0	-10000	0	0
BCL2	-0.22	0.42	-10000	0	-1.6	35	35

×

Signaling events regulated by Ret tyrosine kinase

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.09	0.069	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.2	-9999	-0.51	118	118
JUN	-0.32	0.32	-9999	-0.67	177	177
HRAS	0.012	0.021	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.39	0.32	-9999	-0.61	300	300
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.39	0.32	-9999	-0.61	300	300
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.3	0.25	-9999	-0.51	275	275
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.35	0.3	-9999	-0.55	300	300
GRB7	-0.042	0.12	-9999	-0.31	82	82
RET51/GFRalpha1/GDNF	-0.39	0.32	-9999	-0.61	300	300
MAPKKK cascade	-0.31	0.26	-9999	-0.52	222	222
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.35	0.31	-9999	-0.58	287	287
lamellipodium assembly	-0.24	0.18	-9999	-0.38	276	276
RET51/GFRalpha1/GDNF/SHC	-0.39	0.32	-9999	-0.61	300	300
PIK3CA	0.008	0.066	-9999	-0.82	3	3
RET9/GFRalpha1/GDNF/SHC	-0.29	0.25	-9999	-0.51	275	275
RET9/GFRalpha1/GDNF/Shank3	-0.29	0.25	-9999	-0.51	275	275
MAPK3	-0.32	0.29	-9999	-0.52	300	300
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.12	0.3	-9999	-0.82	75	75
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.31	0.29	-9999	-0.67	128	128
DOK5	-0.1	0.29	-9999	-0.82	66	66
GFRA1	-0.46	0.41	-9999	-0.82	276	276
MAPK8	-0.24	0.23	-9999	-0.54	113	113
HRAS/GTP	-0.36	0.31	-9999	-0.57	300	300
tube development	-0.28	0.24	-9999	-0.48	275	275
MAPK1	-0.32	0.29	-9999	-0.52	300	300
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.18	0.18	-9999	-0.34	275	275
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
PDLIM7	0.01	0.033	-9999	-0.31	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.44	0.38	-9999	-0.67	311	311
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.39	0.32	-9999	-0.61	300	300
RET51/GFRalpha1/GDNF/Dok5	-0.46	0.39	-9999	-0.69	312	312
PRKCA	-0.025	0.18	-9999	-0.82	22	22
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
CREB1	-0.25	0.24	-9999	-0.43	275	275
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.18	0.18	-9999	-0.34	275	275
RET51/GFRalpha1/GDNF/Grb7	-0.42	0.33	-9999	-0.64	300	300
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.17	0.32	-9999	-0.64	135	135
DOK4	0.013	0.015	-9999	-0.31	1	1
JNK cascade	-0.31	0.3	-9999	-0.65	177	177
RET9/GFRalpha1/GDNF/FRS2	-0.29	0.25	-9999	-0.51	275	275
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.18	-9999	-0.34	275	275
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.25	0.24	-9999	-0.43	245	245
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.25	0.24	-9999	-0.41	300	300
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.29	0.31	-9999	-0.47	300	300
PI3K	-0.37	0.34	-9999	-0.62	276	276
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.28	0.24	-9999	-0.48	275	275
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.22	0.21	-9999	-0.53	84	84
RET51/GFRalpha1/GDNF/FRS2	-0.39	0.32	-9999	-0.61	300	300
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.082	0.27	-9999	-0.82	55	55
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.29	0.31	-9999	-0.47	300	300
RET51/GFRalpha1/GDNF/PKC alpha	-0.41	0.35	-9999	-0.64	302	302
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.002	0.041	-9999	-0.31	8	8
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.45	0.37	-9999	-0.68	311	311
Rac1/GTP	-0.29	0.23	-9999	-0.47	276	276
RET9/GFRalpha1/GDNF	-0.32	0.28	-9999	-0.56	275	275
GFRalpha1/GDNF	-0.37	0.32	-9999	-0.64	275	275

×

TCGA08_retinoblastoma

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
CDKN2B	-0.12	0.16	-10000	0	-0.31	200	200
CDKN2C	0.026	0.036	-10000	0	-0.3	4	4
CDKN2A	-0.13	0.16	-10000	0	-0.32	206	206
CCND2	0.07	0.073	0.17	140	-10000	0	140
RB1	-0.069	0.072	-10000	0	-0.17	140	140
CDK4	0.07	0.072	0.17	142	-10000	0	142
CDK6	0.073	0.077	0.18	140	-0.18	2	142
G1/S progression	0.061	0.08	0.17	140	-10000	0	140

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.001	0.013	-9999	-10000	0	0
VLDLR	-0.023	0.17	-9999	-0.82	21	21
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.01	0.033	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.42	0.26	-9999	-0.57	358	358
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.009	0.063	-9999	-0.46	9	9
AKT1	-0.24	0.18	-9999	-0.33	359	359
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
RELN/LRP8/DAB1	-0.39	0.25	-9999	-0.53	357	357
LRPAP1/LRP8	-0.026	0.13	-9999	-0.63	20	20
RELN/LRP8/DAB1/Fyn	-0.37	0.23	-9999	-0.5	357	357
DAB1/alpha3/beta1 Integrin	-0.35	0.23	-9999	-0.84	35	35
long-term memory	-0.37	0.25	-9999	-0.49	359	359
DAB1/LIS1	-0.36	0.24	-9999	-0.48	362	362
DAB1/CRLK/C3G	-0.35	0.23	-9999	-0.46	362	362
PIK3CA	0.008	0.066	-9999	-0.82	3	3
DAB1/NCK2	-0.36	0.24	-9999	-0.48	362	362
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.023	0.16	-9999	-0.64	27	27
CDK5R1	0.012	0.021	-9999	-0.31	2	2
RELN	-0.6	0.37	-9999	-0.82	353	353
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.42	0.26	-9999	-0.57	357	357
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.38	0.26	-9999	-0.51	359	359
MAPK8	-0.002	0.11	-9999	-0.82	9	9
RELN/VLDLR/DAB1	-0.39	0.25	-9999	-0.53	358	358
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.37	0.26	-9999	-0.5	362	362
RELN/LRP8	-0.42	0.26	-9999	-0.57	357	357
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.37	0.23	-9999	-0.5	357	357
PI3K	-0.004	0.05	-9999	-0.63	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.02	-9999	-10000	0	0
RAP1A	-0.31	0.23	-9999	-0.82	29	29
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.003	0.016	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.14	-9999	-0.52	22	22
neuron adhesion	-0.28	0.23	-9999	-0.74	33	33
LRP8	-0.021	0.17	-9999	-0.82	20	20
GSK3B	-0.22	0.17	-9999	-0.62	18	18
RELN/VLDLR/DAB1/Fyn	-0.37	0.23	-9999	-0.5	358	358
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.36	359	359
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.033	0.089	-9999	-0.33	20	20
neuron migration	-0.3	0.22	-9999	-0.42	354	354
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.14	-9999	-0.52	22	22
RELN/VLDLR	-0.4	0.27	-9999	-0.54	362	362

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.042	0.16	-10000	0	-0.6	27	27
NFATC2	-0.24	0.38	-10000	0	-0.81	126	126
NFATC3	-0.083	0.13	-10000	0	-10000	0	0
CD40LG	-0.74	0.57	-10000	0	-1.2	262	262
ITCH	0.051	0.015	-10000	0	-10000	0	0
CBLB	0.051	0.015	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.53	0.52	-10000	0	-1.2	139	139
JUNB	0.003	0.093	-10000	0	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.015	-10000	0	-0.34	1	1
T cell anergy	0.025	0.065	-10000	0	-0.49	1	1
TLE4	-0.25	0.44	-10000	0	-0.87	137	137
Jun/NFAT1-c-4/p21SNFT	-0.67	0.61	-10000	0	-1.2	239	239
AP-1/NFAT1-c-4	-0.9	0.79	-10000	0	-1.5	263	263
IKZF1	-0.18	0.34	-10000	0	-0.72	107	107
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.89	102	102
AP-1/NFAT1	-0.43	0.49	-10000	0	-0.9	214	214
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.86	-10000	0	-1.7	221	221
EGR3	-0.58	0.75	-10000	0	-1.6	133	133
NFAT1/FOXP3	-0.22	0.34	-10000	0	-0.7	127	127
EGR1	-0.16	0.34	-10000	0	-0.82	102	102
JUN	-0.19	0.35	-10000	0	-0.83	109	109
EGR4	-0.035	0.18	-10000	0	-0.72	29	29
mol:Ca2+	0.016	0.01	-10000	0	-10000	0	0
GBP3	-0.17	0.32	-10000	0	-0.7	102	102
FOSL1	-0.029	0.12	-10000	0	-0.33	59	59
NFAT1-c-4/MAF/IRF4	-0.57	0.57	-10000	0	-1.1	238	238
DGKA	-0.16	0.3	-10000	0	-0.66	100	100
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.56	0.56	-10000	0	-1.1	239	239
CTLA4	-0.24	0.38	-10000	0	-0.82	109	109
NFAT1-c-4 (dimer)/EGR1	-0.64	0.67	-10000	0	-1.3	235	235
NFAT1-c-4 (dimer)/EGR4	-0.58	0.57	-10000	0	-1.1	238	238
FOS	-0.22	0.37	-10000	0	-0.83	128	128
IFNG	-0.43	0.54	-10000	0	-1.2	143	143
T cell activation	-0.44	0.43	-10000	0	-0.95	169	169
MAF	0.013	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.37	0.43	0.76	223	-10000	0	223
TNF	-0.6	0.58	-10000	0	-1.1	234	234
FASLG	-0.74	0.79	-10000	0	-1.5	239	239
TBX21	-0.037	0.18	-10000	0	-0.72	29	29
BATF3	-0.006	0.083	-10000	0	-0.33	27	27
PRKCQ	0.005	0.086	-10000	0	-0.82	5	5
PTPN1	-0.16	0.3	-10000	0	-0.68	92	92
NFAT1-c-4/ICER1	-0.55	0.56	-10000	0	-1.1	238	238
GATA3	-0.031	0.19	-10000	0	-0.79	27	27
T-helper 1 cell differentiation	-0.41	0.52	-10000	0	-1.1	144	144
IL2RA	-0.48	0.46	-10000	0	-1	154	154
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.3	-10000	0	-0.66	100	100
E2F1	-0.081	0.15	-10000	0	-0.3	150	150
PPARG	-0.002	0.1	-10000	0	-0.61	12	12
SLC3A2	-0.16	0.3	-10000	0	-0.66	100	100
IRF4	-0.1	0.23	-10000	0	-0.46	119	119
PTGS2	-0.71	0.57	-10000	0	-1.2	252	252
CSF2	-0.78	0.54	-10000	0	-1.2	263	263
JunB/Fra1/NFAT1-c-4	-0.54	0.54	-10000	0	-1	233	233
IL4	-0.33	0.37	-10000	0	-0.95	99	99
IL5	-0.69	0.54	-10000	0	-1.2	248	248
IL2	-0.45	0.44	-10000	0	-0.98	169	169
IL3	-0.097	0.062	-10000	0	-10000	0	0
RNF128	0.049	0.042	-10000	0	-0.88	1	1
NFATC1	-0.37	0.43	-10000	0	-0.77	223	223
CDK4	0.22	0.25	0.6	63	-10000	0	63
PTPRK	-0.16	0.3	-10000	0	-0.66	100	100
IL8	-0.72	0.55	-10000	0	-1.2	251	251
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.13	0.32	-9999	-0.82	83	83
GNB1/GNG2	-0.26	0.24	-9999	-0.6	123	123
mol:DAG	-0.21	0.24	-9999	-0.54	123	123
PLCG1	-0.22	0.25	-9999	-0.56	123	123
YES1	-0.25	0.27	-9999	-0.43	300	300
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.24	0.22	-9999	-0.57	118	118
MAP3K7	-0.17	0.2	-9999	-0.45	115	115
mol:Ca2+	-0.2	0.23	-9999	-0.52	123	123
mol:IP3	-0.21	0.24	-9999	-0.54	123	123
NLK	-0.01	0.01	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.19	0.22	-9999	-0.48	128	128
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.47	300	300
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.25	0.27	-9999	-0.43	300	300
GO:0007205	-0.21	0.23	-9999	-0.53	123	123
WNT6	0.005	0.049	-9999	-0.31	11	11
WNT4	-0.26	0.39	-9999	-0.81	161	161
NFAT1/CK1 alpha	-0.3	0.26	-9999	-0.58	183	183
GNG2	0.012	0.038	-9999	-0.82	1	1
WNT5A	-0.005	0.12	-9999	-0.78	11	11
WNT11	-0.42	0.42	-9999	-0.82	247	247
CDC42	-0.23	0.25	-9999	-0.59	122	122

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.47	300	300
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.005	0.049	-9999	-0.31	11	11
WNT4	-0.26	0.39	-9999	-0.81	161	161
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.005	0.12	-9999	-0.78	11	11
WNT11	-0.42	0.42	-9999	-0.82	247	247

×

FOXA2 and FOXA3 transcription factor networks

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.52	0.54	-9999	-1	215	215
PCK1	-0.35	0.5	-9999	-1.4	72	72
HNF4A	-0.67	0.66	-9999	-1.3	246	246
KCNJ11	-0.49	0.54	-9999	-1	199	199
AKT1	-0.041	0.12	-9999	-0.38	13	13
response to starvation	-0.018	0.034	-9999	-10000	0	0
DLK1	-0.49	0.54	-9999	-1.1	198	198
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.52	0.55	-9999	-1	220	220
TAT	-0.2	0.22	-9999	-0.6	26	26
CEBPB	0.013	0.005	-9999	-10000	0	0
CEBPA	0.005	0.085	-9999	-0.82	5	5
TTR	-0.2	0.22	-9999	-0.76	31	31
PKLR	-0.52	0.55	-9999	-1.1	211	211
APOA1	-0.92	0.89	-9999	-1.7	261	261
CPT1C	-0.53	0.55	-9999	-1	222	222
ALAS1	-0.16	0.21	-9999	-10000	0	0
TFRC	-0.26	0.3	-9999	-0.66	76	76
FOXF1	-0.011	0.093	-9999	-0.76	7	7
NF1	0.021	0.001	-9999	-10000	0	0
HNF1A (dimer)	0.015	0.007	-9999	-10000	0	0
CPT1A	-0.52	0.55	-9999	-1	217	217
HMGCS1	-0.52	0.54	-9999	-1	218	218
NR3C1	0.019	0.016	-9999	-10000	0	0
CPT1B	-0.52	0.54	-9999	-1	216	216
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.67	0.7	-9999	-1.3	234	234
CREB1	0	0.053	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.55	10	10
PDX1	-0.18	0.21	-9999	-10000	0	0
UCP2	-0.52	0.55	-9999	-1.1	211	211
ALDOB	-0.49	0.54	-9999	-1	199	199
AFP	-0.049	0.11	-9999	-0.51	6	6
BDH1	-0.52	0.54	-9999	-1.1	207	207
HADH	-0.48	0.54	-9999	-1	199	199
F2	-0.63	0.64	-9999	-1.3	208	208
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.007	0.09	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.55	61	61
INS	-0.008	0.018	-9999	-10000	0	0
FOXA1	-0.06	0.15	-9999	-0.52	14	14
FOXA3	-0.076	0.17	-9999	-0.35	114	114
FOXA2	-0.56	0.61	-9999	-1.1	223	223
ABCC8	-0.78	0.75	-9999	-1.4	267	267
ALB	-0.1	0.32	-9999	-1.3	31	31

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.26	0.39	-9999	-0.84	152	152
PDGF/PDGFRA/CRKL	-0.2	0.29	-9999	-0.63	152	152
positive regulation of JUN kinase activity	-0.15	0.22	-9999	-0.48	152	152
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.2	0.3	-9999	-0.64	152	152
AP1	-0.51	0.63	-9999	-1.5	135	135
mol:IP3	-0.2	0.31	-9999	-0.65	152	152
PLCG1	-0.2	0.31	-9999	-0.65	152	152
PDGF/PDGFRA/alphaV Integrin	-0.2	0.3	-9999	-0.63	153	153
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.2	0.31	-9999	-0.65	152	152
CAV3	-0.001	0.029	-9999	-0.31	4	4
CAV1	-0.009	0.14	-9999	-0.82	13	13
SHC/Grb2/SOS1	-0.15	0.23	-9999	-0.49	152	152
PDGF/PDGFRA/Shf	-0.2	0.29	-9999	-0.63	152	152
FOS	-0.46	0.61	-9999	-1.4	135	135
JUN	-0.17	0.29	-9999	-0.7	109	109
oligodendrocyte development	-0.2	0.3	-9999	-0.63	153	153
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.2	0.31	-9999	-0.65	152	152
PDGF/PDGFRA	-0.26	0.39	-9999	-0.84	152	152
actin cytoskeleton reorganization	-0.2	0.29	-9999	-0.63	152	152
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.17	0.25	-9999	-0.54	155	155
PDGF/PDGFRA/Crk/C3G	-0.17	0.25	-9999	-0.54	152	152
JAK1	-0.18	0.3	-9999	-0.63	152	152
ELK1/SRF	-0.13	0.24	-9999	-0.49	152	152
SHB	0.013	0	-9999	-10000	0	0
SHF	0.013	0.015	-9999	-0.31	1	1
CSNK2A1	0.028	0.028	-9999	-10000	0	0
GO:0007205	-0.2	0.32	-9999	-0.67	152	152
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.15	0.22	-9999	-0.48	152	152
PDGF/PDGFRA/SHB	-0.2	0.29	-9999	-0.63	152	152
PDGF/PDGFRA/Caveolin-1	-0.21	0.32	-9999	-0.66	155	155
ITGAV	0.01	0.054	-9999	-0.82	2	2
ELK1	-0.18	0.28	-9999	-0.6	152	152
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PDGF/PDGFRA/Crk	-0.2	0.29	-9999	-0.63	152	152
JAK-STAT cascade	-0.18	0.3	-9999	-0.63	152	152
cell proliferation	-0.2	0.29	-9999	-0.63	152	152

×

IL4-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
BCL2L1	-0.59	0.44	-10000	0	-1.1	157	157
STAT6 (cleaved dimer)	-0.64	0.44	-10000	0	-1	250	250
IGHG1	-0.2	0.14	-10000	0	-0.36	56	56
IGHG3	-0.58	0.42	-10000	0	-0.95	224	224
AKT1	-0.32	0.26	-10000	0	-0.72	75	75
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.26	-10000	0	-0.76	54	54
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.74	104	104
THY1	-0.59	0.44	-10000	0	-1.1	155	155
MYB	-0.008	0.12	-10000	0	-0.63	16	16
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.41	0.31	-10000	0	-0.73	173	173
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.74	66	66
SP1	0.02	0.006	-10000	0	-10000	0	0
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
SOCS5	0.03	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.62	0.44	-10000	0	-0.99	238	238
SOCS1	-0.4	0.29	-10000	0	-0.73	127	127
SOCS3	-0.38	0.36	-10000	0	-0.97	80	80
FCER2	-0.58	0.42	-10000	0	-0.97	208	208
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.66	0.48	-10000	0	-1.2	180	180
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.7	41	41
T cell proliferation	-0.6	0.46	-10000	0	-1.1	183	183
IL4R/JAK1	-0.59	0.44	-10000	0	-1.1	167	167
EGR2	-0.93	0.72	-10000	0	-1.6	236	236
JAK2	-0.017	0.045	-10000	0	-0.86	1	1
JAK3	-0.066	0.14	-10000	0	-0.31	120	120
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.008	-10000	0	-10000	0	0
COL1A2	-0.19	0.15	-10000	0	-0.54	31	31
CCL26	-0.61	0.45	-10000	0	-1.1	168	168
IL4R	-0.63	0.47	-10000	0	-1.1	170	170
PTPN6	0.028	0.009	-10000	0	-10000	0	0
IL13RA2	-0.7	0.57	-10000	0	-1.3	201	201
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.34	0.48	-10000	0	-1.2	91	91
ARG1	-0.14	0.11	-10000	0	-10000	0	0
CBL	-0.38	0.3	-10000	0	-0.71	151	151
GTF3A	0.017	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
IL13RA1/JAK2	-0.024	0.045	-10000	0	-0.68	1	1
IRF4/BCL6	-0.31	0.44	-10000	0	-1.1	88	88
CD40LG	-0.12	0.3	-10000	0	-0.8	77	77
MAPK14	-0.39	0.32	-10000	0	-0.76	136	136
mitosis	-0.3	0.24	-10000	0	-0.67	75	75
STAT6	-0.67	0.51	-10000	0	-1.1	215	215
SPI1	0.001	0.071	-10000	0	-0.31	24	24
RPS6KB1	-0.29	0.24	-10000	0	-0.67	62	62
STAT6 (dimer)	-0.67	0.51	-10000	0	-1.1	215	215
STAT6 (dimer)/PARP14	-0.62	0.47	-10000	0	-1.1	204	204
mast cell activation	0.016	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.32	0.28	-10000	0	-0.71	89	89
FRAP1	-0.32	0.26	-10000	0	-0.72	75	75
LTA	-0.61	0.46	-10000	0	-1.1	162	162
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.66	0.5	1.1	217	-10000	0	217
CCL11	-0.58	0.43	-10000	0	-1.1	143	143
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.7	89	89
IL2RG	-0.044	0.19	-10000	0	-0.55	52	52
IL10	-0.61	0.47	-10000	0	-1.1	169	169
IRS1	-0.082	0.27	-10000	0	-0.82	55	55
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.095	-10000	0	-10000	0	0
IL5	-0.6	0.44	-10000	0	-1.1	157	157
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.48	0.33	-10000	0	-0.84	161	161
COL1A1	-0.26	0.24	-10000	0	-0.78	24	24
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.59	0.45	-10000	0	-1.2	122	122
IL2R gamma/JAK3	-0.081	0.18	-10000	0	-0.52	52	52
TFF3	-1.3	0.61	-10000	0	-1.6	391	391
ALOX15	-0.59	0.44	-10000	0	-1.1	157	157
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.51	0.36	-10000	0	-0.86	194	194
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.018	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.3	0.26	-10000	0	-0.68	76	76
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.72	75	75
PI3K	-0.33	0.28	-10000	0	-0.77	75	75
DOK2	0	0.076	-10000	0	-0.38	16	16
ETS1	0.03	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.24	0.21	-10000	0	-0.7	38	38
ITGB3	-0.61	0.47	-10000	0	-1.1	162	162
PIGR	-0.64	0.5	-10000	0	-1.2	168	168
IGHE	0.051	0.035	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.68	38	38
BCL6	0.012	0.038	-10000	0	-0.82	1	1
OPRM1	-0.6	0.44	-10000	0	-1.1	165	165
RETNLB	-0.6	0.44	-10000	0	-1.1	165	165
SELP	-0.6	0.46	-10000	0	-1.1	158	158
AICDA	-0.58	0.42	-10000	0	-1.1	152	152

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.11	0.26	-10000	0	-0.69	35	35
IHH	-0.21	0.37	-10000	0	-0.84	122	122
SHH Np/Cholesterol/GAS1	-0.11	0.21	-10000	0	-0.52	97	97
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.11	0.21	0.51	97	-10000	0	97
SMO/beta Arrestin2	-0.098	0.24	-10000	0	-0.48	124	124
SMO	-0.11	0.26	-10000	0	-0.52	125	125
AKT1	-0.028	0.12	-10000	0	-0.66	2	2
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	-0.001	0.11	-10000	0	-0.82	8	8
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.11	0.25	-10000	0	-0.51	125	125
STIL	-0.08	0.2	-10000	0	-0.6	18	18
DHH N/PTCH2	-0.11	0.24	-10000	0	-0.64	80	80
DHH N/PTCH1	-0.1	0.23	-10000	0	-0.46	128	128
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
DHH	0.006	0.076	-10000	0	-0.82	4	4
PTHLH	-0.16	0.37	-10000	0	-1.2	35	35
determination of left/right symmetry	-0.11	0.25	-10000	0	-0.51	125	125
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.16	0.36	-10000	0	-1.1	35	35
IHH N/Hhip	-0.38	0.4	-10000	0	-0.74	255	255
DHH N/Hhip	-0.25	0.31	-10000	0	-0.64	188	188
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.11	0.25	-10000	0	-0.51	125	125
pancreas development	-0.31	0.4	-10000	0	-0.82	188	188
HHAT	0.012	0.038	-10000	0	-0.82	1	1
PI3K	-0.004	0.05	-10000	0	-0.63	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.15	0.33	-10000	0	-0.82	96	96
somite specification	-0.11	0.25	-10000	0	-0.51	125	125
SHH Np/Cholesterol/PTCH1	-0.09	0.2	-10000	0	-0.43	85	85
SHH Np/Cholesterol/PTCH2	-0.089	0.19	-10000	0	-0.52	79	79
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.52	127	127
SHH	0.007	0.05	-10000	0	-0.63	1	1
catabolic process	-0.12	0.25	-10000	0	-0.51	125	125
SMO/Vitamin D3	-0.094	0.22	-10000	0	-0.44	125	125
SHH Np/Cholesterol/Hhip	-0.2	0.25	-10000	0	-0.51	187	187
LRP2	-0.2	0.37	-10000	0	-0.82	126	126
receptor-mediated endocytosis	-0.2	0.24	-10000	0	-0.72	47	47
SHH Np/Cholesterol/BOC	-0.014	0.075	-10000	0	-0.53	9	9
SHH Np/Cholesterol/CDO	-0.15	0.23	-10000	0	-0.52	140	140
mesenchymal cell differentiation	0.2	0.24	0.51	187	-10000	0	187
mol:Vitamin D3	-0.089	0.21	-10000	0	-0.41	125	125
IHH N/PTCH2	-0.23	0.35	-10000	0	-0.66	178	178
CDON	-0.23	0.38	-10000	0	-0.82	139	139
IHH N/PTCH1	-0.12	0.25	-10000	0	-0.52	125	125
Megalin/LRPAP1	-0.16	0.28	-10000	0	-0.63	126	126
PTCH2	-0.12	0.31	-10000	0	-0.82	78	78
SHH Np/Cholesterol	-0.006	0.036	-10000	0	-0.51	1	1
PTCH1	-0.12	0.25	-10000	0	-0.51	125	125
HHIP	-0.31	0.4	-10000	0	-0.82	188	188

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.21	0.25	-10000	0	-0.51	203	203
regulation of S phase of mitotic cell cycle	-0.13	0.18	-10000	0	-0.34	204	204
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
HRAS	0.011	0.021	-10000	0	-0.32	2	2
SHBG/T-DHT	-0.009	0.072	-10000	0	-0.56	8	8
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0.001	-10000	0	-10000	0	0
MAP2K1	-0.17	0.24	-10000	0	-0.44	202	202
T-DHT/AR	-0.27	0.32	-10000	0	-0.64	202	202
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	128	128
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
mol:GDP	-0.26	0.31	-10000	0	-0.62	204	204
cell proliferation	-0.2	0.28	-10000	0	-0.65	87	87
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
FOS	-0.25	0.4	-10000	0	-0.89	128	128
mol:Ca2+	-0.027	0.031	-10000	0	-0.071	92	92
MAPK3	-0.18	0.26	-10000	0	-0.6	86	86
MAPK1	-0.083	0.13	-10000	0	-0.31	78	78
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	128	128
cAMP biosynthetic process	0.016	0.076	-10000	0	-0.53	8	8
GNG2	0.012	0.038	-10000	0	-0.82	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	128	128
HRAS/GTP	-0.2	0.23	-10000	0	-0.47	202	202
actin cytoskeleton reorganization	-0.003	0.035	-10000	0	-0.44	3	3
SRC	0.012	0.015	-10000	0	-0.32	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	128	128
PI3K	-0.003	0.044	-10000	0	-0.56	3	3
apoptosis	0.16	0.25	0.53	128	-10000	0	128
T-DHT/AR/PELP1	-0.23	0.28	-10000	0	-0.56	202	202
HRAS/GDP	-0.25	0.29	-10000	0	-0.59	203	203
CREB1	-0.18	0.27	-10000	0	-0.57	128	128
RAC1-CDC42/GTP	-0.003	0.036	-10000	0	-0.45	3	3
AR	-0.34	0.41	-10000	0	-0.83	202	202
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.18	0.24	-10000	0	-0.46	202	202
RAC1-CDC42/GDP	-0.24	0.28	-10000	0	-0.56	202	202
T-DHT/AR/PELP1/Src	-0.22	0.25	-10000	0	-0.51	202	202
MAP2K2	-0.17	0.24	-10000	0	-0.44	202	202
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.19	-10000	0	-0.34	204	204
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	-0.001	0.11	-10000	0	-0.82	8	8
Gi family/GNB1/GNG2/GDP	-0.02	0.12	-10000	0	-0.55	16	16
mol:T-DHT	0	0.001	0.002	76	-0.003	50	126
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.043	-10000	0	-0.64	2	2
Gi family/GTP	-0.095	0.12	-10000	0	-0.48	17	17
CDC42	0.013	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	-0.023	0.17	-9999	-0.82	21	21
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.42	0.26	-9999	-0.57	357	357
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.37	0.26	-9999	-0.52	357	357
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.1	0.29	-9999	-0.82	65	65
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.026	0.13	-9999	-0.63	20	20
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.012	0.021	-9999	-0.31	2	2
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	0.004	0.022	-9999	-0.31	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.43	0.26	-9999	-0.57	358	358
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.28	0.2	-9999	-0.73	16	16
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.32	0.23	-9999	-0.45	357	357
RELN	-0.6	0.37	-9999	-0.82	353	353
PAFAH/LIS1	-0.049	0.2	-9999	-0.55	65	65
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.22	0.14	-9999	-0.55	16	16
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.25	0.19	-9999	-0.34	363	363
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.3	0.22	-9999	-0.42	357	357
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.024	0	-9999	-10000	0	0
PAFAH1B3	0.011	0.03	-9999	-0.31	4	4
PAFAH1B2	-0.002	0.11	-9999	-0.82	9	9
MAP1B/LIS1/Dynein heavy chain	0.027	0.003	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.28	0.17	-9999	-0.7	16	16
LRP8	-0.021	0.17	-9999	-0.82	20	20
NDEL1/Katanin 60	-0.28	0.2	-9999	-0.73	16	16
P39/CDK5	-0.32	0.23	-9999	-0.45	357	357
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.34	0.24	-9999	-0.48	357	357
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.36	0.23	-9999	-0.49	358	358
RELN/VLDLR	-0.4	0.27	-9999	-0.54	362	362
CDC42	0	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.011	0.081	-9999	-0.56	9	9
NFATC2	-0.1	0.22	-9999	-0.58	83	83
NFATC3	0	0.027	-9999	-10000	0	0
CD40LG	-0.44	0.41	-9999	-0.87	197	197
PTGS2	-0.42	0.4	-9999	-0.86	183	183
JUNB	0.003	0.093	-9999	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.015	-9999	-10000	0	0
CALM1	0.008	0.008	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.83	109	109
mol:Ca2+	-0.01	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.004	-9999	-10000	0	0
FOSL1	-0.029	0.12	-9999	-0.33	59	59
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.59	169	169
FOS	-0.22	0.37	-9999	-0.83	128	128
IFNG	-0.44	0.41	-9999	-0.86	197	197
AP-1/NFAT1-c-4	-0.53	0.51	-9999	-1	213	213
FASLG	-0.42	0.39	-9999	-0.83	187	187
NFAT1-c-4/ICER1	-0.11	0.2	-9999	-0.5	91	91
IL2RA	-0.41	0.38	-9999	-0.84	180	180
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.36	-9999	-0.77	259	259
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.5	97	97
IL4	-0.4	0.36	-9999	-0.8	178	178
IL2	-0.012	0.026	-9999	-10000	0	0
IL3	-0.032	0.03	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.006	0.083	-9999	-0.33	27	27
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.015	-9999	-0.31	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.16	0.3	0.69	115	-10000	0	115
KIRREL	-0.067	0.23	-10000	0	-0.85	39	39
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.17	0.3	-10000	0	-0.69	115	115
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.13	0.24	-10000	0	-0.54	115	115
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.075	0.2	-10000	0	-0.41	115	115
FYN	-0.11	0.24	-10000	0	-0.51	115	115
mol:Ca2+	-0.13	0.24	-10000	0	-0.54	115	115
mol:DAG	-0.13	0.24	-10000	0	-0.54	115	115
NPHS2	-0.016	0.053	-10000	0	-0.9	1	1
mol:IP3	-0.13	0.24	-10000	0	-0.54	115	115
regulation of endocytosis	-0.11	0.21	-10000	0	-0.48	115	115
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.55	115	115
establishment of cell polarity	-0.16	0.3	-10000	0	-0.69	115	115
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.22	-10000	0	-0.5	115	115
Nephrin/NEPH1/beta Arrestin2	-0.11	0.22	-10000	0	-0.48	115	115
NPHS1	-0.15	0.32	-10000	0	-0.83	89	89
Nephrin/NEPH1/podocin	-0.12	0.23	-10000	0	-0.52	115	115
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.13	0.24	-10000	0	-0.54	115	115
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.13	0.24	-10000	0	-0.54	115	115
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.11	0.24	-10000	0	-0.51	119	119
cytoskeleton organization	-0.1	0.26	-10000	0	-0.54	115	115
Nephrin/NEPH1	-0.13	0.24	-10000	0	-0.53	115	115
Nephrin/NEPH1/ZO-1	-0.14	0.26	-10000	0	-0.57	115	115

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.001	0.026	-10000	0	-0.55	1	1
fibroblast growth factor receptor signaling pathway	-0.001	0.026	-10000	0	-0.54	1	1
LAMA1	-0.05	0.22	-10000	0	-0.81	37	37
PRNP	0.012	0.038	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.095	0.22	-10000	0	-0.63	71	71
SMAD2	0.028	0.049	-10000	0	-0.49	3	3
GPC1/PrPc/Cu2+	-0.001	0.026	-10000	0	-0.56	1	1
GPC1/Laminin alpha1	-0.048	0.17	-10000	0	-0.63	36	36
TDGF1	-0.34	0.41	-10000	0	-0.82	202	202
CRIPTO/GPC1	-0.26	0.31	-10000	0	-0.63	202	202
APP/GPC1	0	0.009	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.21	0.28	-10000	0	-0.54	202	202
FLT1	0.012	0.038	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.008	0.05	-10000	0	-0.55	3	3
SERPINC1	0.007	0.042	-10000	0	-0.31	8	8
FYN	-0.21	0.28	-10000	0	-0.54	202	202
FGR	-0.21	0.28	-10000	0	-0.54	202	202
positive regulation of MAPKKK cascade	-0.28	0.32	-10000	0	-0.62	204	204
SLIT2	-0.11	0.3	-10000	0	-0.8	74	74
GPC1/NRG	-0.06	0.18	-10000	0	-0.63	45	45
NRG1	-0.066	0.24	-10000	0	-0.8	47	47
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.005	0.059	-10000	0	-0.71	3	3
LYN	-0.21	0.28	-10000	0	-0.54	202	202
mol:Spermine	0.012	0.01	-10000	0	-10000	0	0
cell growth	-0.001	0.026	-10000	0	-0.54	1	1
BMP signaling pathway	-0.013	0.015	0.31	1	-10000	0	1
SRC	-0.21	0.28	-10000	0	-0.55	202	202
TGFBR1	0.005	0.051	-10000	0	-0.31	12	12
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.25	0.37	-10000	0	-0.69	182	182
GPC1	0.013	0.015	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.005	0.051	-10000	0	-0.31	12	12
VEGFA	0.008	0.066	-10000	0	-0.82	3	3
BLK	-0.38	0.38	-10000	0	-0.67	276	276
HCK	-0.22	0.28	-10000	0	-0.55	202	202
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.012	0.038	-10000	0	-0.82	1	1
VEGFR1 homodimer	0.012	0.038	-10000	0	-0.82	1	1
TGFBR2	0.008	0.066	-10000	0	-0.82	3	3
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.004	0.027	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.2	0.28	-10000	0	-0.63	133	133
LCK	-0.23	0.28	-10000	0	-0.55	207	207
neuron differentiation	-0.06	0.18	-10000	0	-0.63	45	45
PrPc/Cu2+	-0.001	0.029	-10000	0	-0.64	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.008	0.066	-10000	0	-0.82	3	3

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.051	0.14	-9999	-0.53	10	10
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.68	63	63
EDN1	-0.043	0.12	-9999	-0.74	7	7
EDN3	-0.4	0.42	-9999	-0.82	238	238
EDN2	-0.015	0.12	-9999	-0.41	33	33
HRAS/GDP	-0.1	0.24	-9999	-0.54	77	77
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.083	0.18	-9999	-0.4	76	76
ADCY4	-0.096	0.19	-9999	-0.5	68	68
ADCY5	-0.16	0.25	-9999	-0.56	114	114
ADCY6	-0.096	0.19	-9999	-0.5	68	68
ADCY7	-0.096	0.19	-9999	-0.5	68	68
ADCY1	-0.1	0.2	-9999	-0.52	70	70
ADCY2	-0.14	0.24	-9999	-0.55	102	102
ADCY3	-0.096	0.19	-9999	-0.5	68	68
ADCY8	-0.2	0.2	-9999	-0.54	94	94
ADCY9	-0.096	0.19	-9999	-0.5	68	68
arachidonic acid secretion	-0.17	0.32	-9999	-0.64	132	132
ETB receptor/Endothelin-1/Gq/GTP	-0.094	0.21	-9999	-0.43	115	115
GNAO1	-0.017	0.15	-9999	-0.72	20	20
HRAS	0.01	0.021	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.014	0.16	-9999	-0.51	9	9
ETA receptor/Endothelin-1/Gs/GTP	-0.083	0.22	-9999	-0.53	69	69
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.067	0.17	-9999	-0.5	36	36
EDNRB	0.004	0.087	-9999	-0.84	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.16	0.24	-9999	-0.64	52	52
CYSLTR1	-0.059	0.17	-9999	-0.75	14	14
SLC9A1	-0.021	0.075	-9999	-0.31	5	5
mol:GDP	-0.12	0.25	-9999	-0.56	87	87
SLC9A3	-0.046	0.19	-9999	-0.79	20	20
RAF1	-0.15	0.3	-9999	-0.58	124	124
JUN	-0.28	0.52	-9999	-1.2	117	117
JAK2	-0.052	0.14	-9999	-0.54	10	10
mol:IP3	-0.11	0.22	-9999	-0.5	93	93
ETA receptor/Endothelin-1	-0.034	0.2	-9999	-0.51	22	22
PLCB1	0.009	0.039	-9999	-0.83	1	1
PLCB2	0.005	0.043	-9999	-0.32	8	8
ETA receptor/Endothelin-3	-0.33	0.34	-9999	-0.66	237	237
FOS	-0.26	0.48	-9999	-1	130	130
Gai/GDP	-0.003	0.13	-9999	-0.64	17	17
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.12	0.23	-9999	-0.6	51	51
BCAR1	0.013	0.002	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.5	93	93
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.093	0.28	-9999	-0.82	61	61
Gs family/GDP	-0.18	0.25	-9999	-0.58	112	112
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.46	101	101
MAPK14	-0.062	0.17	-9999	-0.47	32	32
TRPC6	-0.14	0.3	-9999	-0.74	60	60
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.82	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.074	0.18	-9999	-0.4	82	82
ETB receptor/Endothelin-2	-0.026	0.1	-9999	-0.64	11	11
ETB receptor/Endothelin-3	-0.32	0.32	-9999	-0.64	239	239
ETB receptor/Endothelin-1	-0.019	0.12	-9999	-0.63	11	11
MAPK3	-0.23	0.44	-9999	-0.89	135	135
MAPK1	-0.23	0.44	-9999	-0.9	134	134
Rac1/GDP	-0.1	0.24	-9999	-0.55	68	68
cAMP biosynthetic process	-0.14	0.21	-9999	-0.54	77	77
MAPK8	-0.17	0.34	-9999	-0.63	130	130
SRC	0.012	0.015	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.009	0.078	-9999	-0.35	9	9
p130Cas/CRK/Src/PYK2	-0.13	0.29	-9999	-0.62	91	91
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.54	75	75
COL1A2	-0.036	0.16	-9999	-0.51	19	19
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.63	8	8
mol:DAG	-0.11	0.23	-9999	-0.51	93	93
MAP2K2	-0.18	0.35	-9999	-0.69	136	136
MAP2K1	-0.18	0.35	-9999	-0.69	138	138
EDNRA	-0.037	0.098	-9999	-0.54	4	4
positive regulation of muscle contraction	-0.036	0.12	-9999	-0.49	8	8
Gq family/GDP	-0.19	0.29	-9999	-0.66	112	112
HRAS/GTP	-0.13	0.26	-9999	-0.57	93	93
PRKCH	-0.1	0.22	-9999	-0.51	79	79
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.26	-9999	-0.55	96	96
PRKCB	-0.12	0.23	-9999	-0.52	89	89
PRKCE	-0.1	0.23	-9999	-0.52	84	84
PRKCD	-0.1	0.22	-9999	-0.51	83	83
PRKCG	-0.11	0.22	-9999	-0.52	80	80
regulation of vascular smooth muscle contraction	-0.31	0.56	-9999	-1.2	130	130
PRKCQ	-0.11	0.23	-9999	-0.52	81	81
PLA2G4A	-0.2	0.36	-9999	-0.72	132	132
GNA14	-0.18	0.36	-9999	-0.83	112	112
GNA15	-0.015	0.093	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA11	-0.005	0.11	-9999	-0.82	9	9
Rac1/GTP	-0.014	0.16	-9999	-0.53	8	8
MMP1	-0.096	0.16	-9999	-10000	0	0

×

IGF1 pathway

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
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.13	0.24	-10000	0	-0.46	155	155
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.021	-10000	0	-0.31	2	2
IRS1/Crk	-0.13	0.24	-10000	0	-0.46	155	155
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.22	-10000	0	-0.53	112	112
AKT1	-0.092	0.22	-10000	0	-0.78	15	15
BAD	-0.078	0.2	-10000	0	-0.71	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.13	0.24	-10000	0	-0.46	155	155
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.24	-10000	0	-0.46	155	155
RAF1	-0.068	0.19	-10000	0	-0.66	15	15
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.21	-10000	0	-0.43	155	155
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.16	0.24	-10000	0	-0.5	155	155
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
RPS6KB1	-0.092	0.22	-10000	0	-0.78	15	15
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.059	0.17	-10000	0	-0.54	15	15
PXN	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.19	-10000	0	-0.73	13	13
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.18	-10000	0	-0.42	112	112
IGF-1R heterotetramer	-0.019	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.15	0.22	-10000	0	-0.46	155	155
Crk/p130 Cas/Paxillin	-0.13	0.2	-10000	0	-0.44	112	112
IGF1R	-0.019	0.048	-10000	0	-10000	0	0
IGF1	-0.2	0.36	-10000	0	-0.82	118	118
IRS2/Crk	-0.11	0.23	-10000	0	-0.43	155	155
PI3K	-0.14	0.22	-10000	0	-0.44	155	155
apoptosis	0.059	0.18	0.58	15	-10000	0	15
HRAS/GDP	-0.001	0.014	-10000	0	-10000	0	0
PRKCD	-0.11	0.24	-10000	0	-0.53	112	112
RAF1/14-3-3 E	-0.05	0.17	-10000	0	-0.54	15	15
BAD/14-3-3	-0.064	0.19	-10000	0	-0.63	15	15
PRKCZ	-0.092	0.22	-10000	0	-0.78	15	15
Crk/p130 Cas/Paxillin/FAK1	-0.1	0.16	-10000	0	-0.64	15	15
PTPN1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.12	0.26	-10000	0	-0.57	112	112
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.19	-10000	0	-0.46	112	112
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.13	0.24	-10000	0	-0.45	155	155
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.13	0.24	-10000	0	-0.46	155	155
IRS1	-0.15	0.25	-10000	0	-0.5	155	155
IRS2	-0.13	0.24	-10000	0	-0.46	155	155
IGF-1R heterotetramer/IGF1	-0.17	0.28	-10000	0	-0.66	112	112
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.1	0.23	-10000	0	-0.45	113	113
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.24	-10000	0	-0.53	113	113
SHC1	0.013	0	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.045	0.094	0.34	4	-10000	0	4
SMARCC2	0.014	0.014	-10000	0	-10000	0	0
SMARCC1	0.013	0.014	-10000	0	-10000	0	0
TBX21	-0.16	0.28	-10000	0	-0.83	48	48
SUMO2	0.014	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.05	-10000	0	-0.31	11	11
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.003	0.093	-10000	0	-0.82	6	6
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.33	59	-0.5	6	65
PRL	-0.089	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.25	0.31	0.58	154	-0.5	19	173
RELA	-0.036	0.089	-10000	0	-0.27	1	1
FGG	0.24	0.19	0.52	106	-10000	0	106
GR beta/TIF2	0.084	0.23	0.35	66	-0.56	44	110
IFNG	-0.5	0.51	-10000	0	-1.1	155	155
apoptosis	0.037	0.24	0.51	57	-0.56	2	59
CREB1	0.011	0.023	-10000	0	-10000	0	0
histone acetylation	-0.072	0.17	-10000	0	-0.44	46	46
BGLAP	-0.099	0.15	-10000	0	-0.52	15	15
GR/PKAc	0.13	0.1	0.34	32	-0.41	1	33
NF kappa B1 p50/RelA	-0.073	0.16	-10000	0	-0.45	32	32
SMARCD1	0.013	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.095	0.27	95	-10000	0	95
GATA3	-0.027	0.19	-10000	0	-0.78	27	27
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.58	34	34
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.064	0.23	0.51	46	-0.74	5	51
CSN2	0.2	0.14	0.42	81	-10000	0	81
BRG1/BAF155/BAF170/BAF60A	0.017	0.05	-10000	0	-10000	0	0
NFATC1	0	0.11	-10000	0	-0.82	9	9
POU2F1	0.013	0.015	-10000	0	-0.3	1	1
CDKN1A	0.023	0.056	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.013	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	310	310
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.047	0.16	0.34	17	-0.47	15	32
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.073	0.44	0.49	46	-0.88	102	148
JUN	-0.34	0.3	-10000	0	-0.68	176	176
IL4	-0.13	0.18	-10000	0	-0.7	19	19
CDK5R1	0.012	0.022	-10000	0	-0.32	2	2
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.37	0.41	-10000	0	-0.81	188	188
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.34	38	-0.48	5	43
cortisol/GR alpha (monomer)	0.37	0.3	0.69	181	-10000	0	181
NCOA2	-0.063	0.24	-10000	0	-0.82	44	44
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.36	-10000	0	-0.85	128	128
AP-1/NFAT1-c-4	-0.56	0.48	-10000	0	-0.96	237	237
AFP	-0.22	0.22	-10000	0	-0.68	36	36
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.52	33	-10000	0	33
TP53	0.032	0.023	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.48	0.37	-10000	0	-0.82	188	188
KRT14	-0.24	0.18	-10000	0	-0.57	37	37
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.064	0.067	-10000	0	-10000	0	0
HDAC1	0.011	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.013	-10000	0	-10000	0	0
AP-1	-0.57	0.49	-10000	0	-0.97	238	238
MAPK14	0.014	0.012	-10000	0	-10000	0	0
MAPK10	0.013	0.04	-10000	0	-0.83	1	1
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.55	0.53	-10000	0	-1	204	204
interleukin-1 receptor activity	0.017	0.013	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	0.015	0.05	-10000	0	-0.31	11	11
CGA	-0.13	0.16	-10000	0	-0.53	25	25
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.38	173	-10000	0	173
MAPK3	0.014	0.013	-10000	0	-10000	0	0
MAPK1	0.014	0.012	-10000	0	-10000	0	0
ICAM1	-0.26	0.27	-10000	0	-0.64	117	117
NFKB1	-0.038	0.098	-10000	0	-0.95	1	1
MAPK8	-0.19	0.2	-10000	0	-0.48	115	115
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.031	0.24	0.52	55	-0.55	3	58
BAX	0.028	0.032	-10000	0	-10000	0	0
POMC	-0.55	0.69	-10000	0	-1.6	122	122
EP300	0.065	0.067	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.33	0.24	0.6	166	-10000	0	166
proteasomal ubiquitin-dependent protein catabolic process	0.088	0.071	0.25	28	-10000	0	28
SGK1	0.1	0.24	-10000	0	-1.4	11	11
IL13	-0.3	0.25	-10000	0	-0.78	66	66
IL6	-0.41	0.54	-10000	0	-1.1	143	143
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.74	37	37
IL2	-0.36	0.27	-10000	0	-0.71	138	138
CDK5	0.013	0.007	-10000	0	-10000	0	0
PRKACB	0.012	0.038	-10000	0	-0.82	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.27	0.32	-10000	0	-0.71	110	110
CDK5R1/CDK5	0.007	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.032	0.12	-10000	0	-0.56	3	3
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.55	167	-10000	0	167
SMARCA4	0.014	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.41	104	-0.39	1	105
NF kappa B1 p50/RelA/Cbp	0.018	0.16	-10000	0	-0.52	5	5
JUN (dimer)	-0.33	0.3	-10000	0	-0.68	176	176
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.41	-10000	0	-0.94	105	105
NR3C1	0.22	0.19	0.5	115	-10000	0	115
NR4A1	-0.31	0.41	-10000	0	-0.76	202	202
TIF2/SUV420H1	-0.058	0.18	-10000	0	-0.63	44	44
MAPKKK cascade	0.037	0.24	0.51	57	-0.56	2	59
cortisol/GR alpha (dimer)/Src-1	0.32	0.24	0.58	178	-10000	0	178
PBX1	0.012	0.038	-10000	0	-0.82	1	1
POU1F1	0.007	0.008	-10000	0	-10000	0	0
SELE	-0.35	0.5	-10000	0	-1.2	96	96
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.42	104	-10000	0	104
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.55	167	-10000	0	167
mol:cortisol	0.21	0.19	0.4	192	-10000	0	192
MMP1	-0.22	0.15	-10000	0	-0.44	63	63

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.066	-10000	0	-0.83	3	3
EFNB1	0	0.12	-10000	0	-0.64	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.25	0.24	-10000	0	-0.52	202	202
Ephrin B2/EPHB1-2	-0.2	0.25	-10000	0	-0.5	189	189
neuron projection morphogenesis	-0.24	0.23	-10000	0	-0.5	202	202
Ephrin B1/EPHB1-2/Tiam1	-0.27	0.27	-10000	0	-0.57	202	202
DNM1	-0.016	0.15	-10000	0	-0.8	17	17
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.006	0.084	-10000	0	-0.8	5	5
YES1	-0.008	0.1	-10000	0	-1	5	5
Ephrin B1/EPHB1-2/NCK2	-0.19	0.24	-10000	0	-0.47	202	202
PI3K	0.004	0.11	-10000	0	-1.1	5	5
mol:GDP	-0.27	0.26	-10000	0	-0.56	202	202
ITGA2B	-0.073	0.26	-10000	0	-0.82	50	50
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.008	0.1	-10000	0	-1	5	5
MAP3K7	-0.011	0.087	-10000	0	-0.85	5	5
FGR	-0.01	0.1	-10000	0	-1	5	5
TIAM1	-0.17	0.16	-10000	0	-0.82	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.042	0.2	-10000	0	-0.53	62	62
LYN	-0.008	0.1	-10000	0	-1	5	5
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.099	-10000	0	-0.98	5	5
Ephrin B1/EPHB1-2	-0.018	0.093	-10000	0	-0.92	5	5
SRC	-0.01	0.1	-10000	0	-1	5	5
ITGB3	-0.011	0.14	-10000	0	-0.82	14	14
EPHB1	-0.31	0.41	-10000	0	-0.82	187	187
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.083	0.23	-10000	0	-0.68	59	59
BLK	-0.065	0.14	-10000	0	-1.1	5	5
HCK	-0.012	0.1	-10000	0	-1	5	5
regulation of stress fiber formation	0.19	0.24	0.47	202	-10000	0	202
MAPK8	0.006	0.12	-10000	0	-0.78	10	10
Ephrin B1/EPHB1-2/RGS3	-0.19	0.24	-10000	0	-0.47	202	202
endothelial cell migration	-0.005	0.076	-10000	0	-0.74	5	5
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.006	0.098	-10000	0	-0.94	5	5
regulation of focal adhesion formation	0.19	0.24	0.47	202	-10000	0	202
chemotaxis	0.19	0.24	0.47	202	-10000	0	202
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
Rac1/GTP	-0.24	0.24	-10000	0	-0.52	202	202
angiogenesis	-0.018	0.092	-10000	0	-0.91	5	5
LCK	-0.014	0.11	-10000	0	-1.1	5	5

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.22	0.56	-10000	0	-1.2	86	86
IL23A	-0.23	0.57	-10000	0	-1.3	89	89
NF kappa B1 p50/RelA/I kappa B alpha	-0.3	0.48	-10000	0	-1.2	87	87
positive regulation of T cell mediated cytotoxicity	-0.26	0.63	-10000	0	-1.4	90	90
ITGA3	-0.2	0.52	-10000	0	-1.2	79	79
IL17F	-0.11	0.35	-10000	0	-0.74	77	77
IL12B	-0.001	0.1	-10000	0	-0.57	11	11
STAT1 (dimer)	-0.24	0.59	-10000	0	-1.3	89	89
CD4	-0.2	0.51	-10000	0	-1.2	79	79
IL23	-0.24	0.54	-10000	0	-1.2	88	88
IL23R	-0.005	0.099	-10000	0	-10000	0	0
IL1B	-0.24	0.6	-10000	0	-1.4	82	82
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.2	0.51	-10000	0	-1.2	82	82
TYK2	0.014	0.023	-10000	0	-10000	0	0
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
STAT3	0.013	0	-10000	0	-10000	0	0
IL18RAP	-0.026	0.17	-10000	0	-0.8	22	22
IL12RB1	-0.021	0.12	-10000	0	-0.37	44	44
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
IL12Rbeta1/TYK2	-0.009	0.093	-10000	0	-0.68	4	4
IL23R/JAK2	-0.002	0.13	-10000	0	-0.68	1	1
positive regulation of chronic inflammatory response	-0.26	0.63	-10000	0	-1.4	90	90
natural killer cell activation	0.001	0.009	0.036	1	-10000	0	1
JAK2	0.02	0.048	-10000	0	-0.86	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
NFKB1	0.011	0.039	-10000	0	-0.83	1	1
RELA	0.013	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.22	0.51	-10000	0	-1.1	88	88
ALOX12B	-0.22	0.52	-10000	0	-1.2	84	84
CXCL1	-0.23	0.54	-10000	0	-1.3	79	79
T cell proliferation	-0.26	0.63	-10000	0	-1.4	90	90
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.063	0.28	-10000	0	-0.57	67	67
PI3K	-0.31	0.49	-10000	0	-1.2	90	90
IFNG	-0.02	0.055	-10000	0	-0.13	72	72
STAT3 (dimer)	-0.29	0.45	-10000	0	-1.2	87	87
IL18R1	-0.031	0.15	-10000	0	-0.43	47	47
IL23/IL23R/JAK2/TYK2/SOCS3	-0.1	0.33	-10000	0	-0.72	64	64
IL18/IL18R	-0.068	0.18	-10000	0	-0.56	46	46
macrophage activation	-0.015	0.018	-10000	0	-0.044	90	90
TNF	-0.28	0.63	-10000	0	-1.4	99	99
STAT3/STAT4	-0.32	0.5	-10000	0	-1.3	90	90
STAT4 (dimer)	-0.26	0.6	-10000	0	-1.3	90	90
IL18	-0.04	0.16	-10000	0	-0.41	58	58
IL19	-0.2	0.51	-10000	0	-1.1	85	85
STAT5A (dimer)	-0.24	0.59	-10000	0	-1.3	87	87
STAT1	0.006	0.049	-10000	0	-0.31	11	11
SOCS3	-0.034	0.19	-10000	0	-0.8	28	28
CXCL9	-0.3	0.64	-10000	0	-1.4	109	109
MPO	-0.2	0.52	-10000	0	-1.1	87	87
positive regulation of humoral immune response	-0.26	0.63	-10000	0	-1.4	90	90
IL23/IL23R/JAK2/TYK2	-0.3	0.75	-10000	0	-1.6	88	88
IL6	-0.34	0.66	-10000	0	-1.3	129	129
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.001	0.017	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.009	0.036	1	-10000	0	1
CD3E	-0.24	0.58	-10000	0	-1.3	91	91
keratinocyte proliferation	-0.26	0.63	-10000	0	-1.4	90	90
NOS2	-0.21	0.51	-10000	0	-1.2	85	85

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.62	75	75
FYN	-0.11	0.35	-10000	0	-0.8	83	83
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.66	86	86
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.054	0.22	-10000	0	-0.47	88	88
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.05	-10000	0	-0.18	11	11
MAP3K8	-0.001	0.11	-10000	0	-0.82	8	8
mol:Ca2+	-0.031	0.05	-10000	0	-0.12	104	104
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.1	0.33	-10000	0	-0.73	90	90
TRPV6	-0.18	0.34	-10000	0	-0.8	107	107
CD28	-0.043	0.19	-10000	0	-0.59	45	45
SHC1	-0.11	0.35	-10000	0	-0.8	85	85
receptor internalization	-0.14	0.38	-10000	0	-0.83	94	94
PRF1	-0.12	0.36	-10000	0	-0.9	69	69
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.037	0.18	-10000	0	-0.38	87	87
LAT	-0.12	0.35	-10000	0	-0.81	85	85
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.095	0.27	-10000	0	-0.72	72	72
CD3E	-0.071	0.25	-10000	0	-0.76	53	53
CD3G	-0.15	0.33	-10000	0	-0.79	96	96
RASGRP2	0	0.031	-10000	0	-0.19	6	6
RASGRP1	-0.05	0.22	-10000	0	-0.47	90	90
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
RASSF5	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.068	-10000	0	-0.12	62	62
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.056	0.09	-10000	0	-0.25	61	61
PRKCA	-0.061	0.13	-10000	0	-0.3	95	95
GRAP2	-0.042	0.21	-10000	0	-0.78	34	34
mol:IP3	-0.052	0.23	0.28	83	-0.47	84	167
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.15	0.42	-10000	0	-0.98	81	81
ORAI1	0.087	0.16	0.39	100	-10000	0	100
CSK	-0.12	0.36	-10000	0	-0.82	85	85
B7 family/CD28	-0.2	0.35	-10000	0	-0.75	112	112
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.16	0.43	-10000	0	-0.96	90	90
PTPN6	-0.12	0.36	-10000	0	-0.84	84	84
VAV1	-0.12	0.35	-10000	0	-0.79	89	89
Monovalent TCR/CD3	-0.16	0.41	-10000	0	-0.73	120	120
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.86	81	81
PAG1	-0.12	0.36	-10000	0	-0.82	85	85
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.16	0.43	-10000	0	-0.96	89	89
CD80	-0.07	0.25	-10000	0	-0.81	49	49
CD86	-0.009	0.11	-10000	0	-0.42	24	24
PDK1/CARD11/BCL10/MALT1	-0.069	0.11	-10000	0	-0.3	69	69
HRAS	0.012	0.021	-10000	0	-0.31	2	2
GO:0035030	-0.11	0.3	-10000	0	-0.63	96	96
CD8A	-0.05	0.22	-10000	0	-0.83	36	36
CD8B	-0.091	0.27	-10000	0	-0.73	68	68
PTPRC	-0.034	0.18	-10000	0	-0.59	37	37
PDK1/PKC theta	-0.068	0.27	-10000	0	-0.6	86	86
CSK/PAG1	-0.11	0.34	-10000	0	-0.82	79	79
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.015	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.15	0.32	-10000	0	-0.78	89	89
STIM1	0.047	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.092	-10000	0	-0.18	55	55
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.43	-10000	0	-0.93	94	94
mol:DAG	-0.071	0.18	-10000	0	-0.41	87	87
RAP1A/GDP	0.006	0.03	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.023	0.16	-10000	0	-0.64	27	27
cytotoxic T cell degranulation	-0.11	0.34	-10000	0	-0.85	69	69
RAP1A/GTP	-0.003	0.009	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.074	0.26	-10000	0	-0.57	90	90
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.081	0.29	0.3	75	-0.62	87	162
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.022	0.16	-10000	0	-0.62	27	27
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.26	-10000	0	-0.63	87	87
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.01	0.054	-10000	0	-0.82	2	2
CD8 heterodimer	-0.11	0.3	-10000	0	-0.77	73	73
CARD11	-0.073	0.17	-10000	0	-0.35	115	115
PRKCB	-0.059	0.13	-10000	0	-0.3	88	88
PRKCE	-0.052	0.12	-10000	0	-0.3	73	73
PRKCQ	-0.091	0.31	-10000	0	-0.69	87	87
LCP2	0.009	0.039	-10000	0	-0.31	7	7
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.04	0.19	-10000	0	-0.4	88	88
IKK complex	0.013	0.069	-10000	0	-0.12	52	52
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.017	0.14	-10000	0	-0.3	70	70
PDPK1	-0.047	0.21	-10000	0	-0.46	84	84
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.46	-10000	0	-1.1	84	84

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.27	0.33	-9999	-0.6	215	215
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.047	0.21	-9999	-0.7	41	41
SMAD9	-0.22	0.28	-9999	-0.6	164	164
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.096	0.2	-9999	-0.37	159	159
BMP7/USAG1	-0.33	0.32	-9999	-0.63	251	251
SMAD5/SKI	-0.084	0.2	-9999	-0.53	28	28
SMAD1	0.019	0.045	-9999	-10000	0	0
BMP2	-0.021	0.17	-9999	-0.82	20	20
SMAD1/SMAD1/SMAD4	-0.001	0.001	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.26	0.39	-9999	-0.82	159	159
BMPR1A-1B/BAMBI	-0.19	0.26	-9999	-0.56	159	159
AHSG	-0.018	0.085	-9999	-0.31	37	37
CER1	0	0.003	-9999	-10000	0	0
BMP2-4/CER1	-0.04	0.14	-9999	-0.55	33	33
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.078	0.2	-9999	-0.63	32	32
BMP2-4 (homodimer)	-0.046	0.16	-9999	-0.63	33	33
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.5	159	159
RGMA	-0.018	0.16	-9999	-0.82	18	18
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.089	0.19	-9999	-0.58	29	29
BMP2-4/USAG1	-0.32	0.3	-9999	-0.58	267	267
SMAD6/SMURF1/SMAD5	-0.084	0.2	-9999	-0.53	28	28
SOSTDC1	-0.42	0.42	-9999	-0.82	252	252
BMP7/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.5	159	159
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.013	0.015	-9999	-0.31	1	1
HFE2	0.001	0.033	-9999	-0.31	5	5
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.051	0.16	-9999	-0.56	42	42
SMAD5/SMAD5/SMAD4	-0.084	0.2	-9999	-0.53	28	28
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.094	0.14	-9999	-0.49	29	29
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.016	0.056	-9999	-0.4	1	1
SMAD1/SKI	0.026	0.043	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.052	0.15	-9999	-0.57	33	33
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.2	0.36	-9999	-0.73	141	141
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.008	0.065	-9999	-0.55	7	7
BMPR1A-1B (homodimer)	-0.21	0.3	-9999	-0.63	159	159
CHRDL1	-0.58	0.38	-9999	-0.82	342	342
ENDOFIN/SMAD1	0.026	0.043	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.006	0.008	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.002	0.08	-9999	-0.37	19	19
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.42	0.28	-9999	-0.59	348	348
BMP2-4/GREM1	-0.18	0.28	-9999	-0.61	133	133
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.19	0.28	-9999	-0.55	164	164
SMAD1/SMAD6	0.026	0.043	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.013	0	-9999	-10000	0	0
BMP6	0.013	0.015	-9999	-0.31	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.067	0.16	-9999	-0.5	29	29
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.026	0.043	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.001	0.1	-9999	-0.82	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.2	0.32	-9999	-0.79	86	86
CHRD	-0.004	0.12	-9999	-0.82	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.095	0.2	-9999	-0.62	29	29
BMP4	-0.014	0.14	-9999	-0.64	20	20
FST	-0.2	0.36	-9999	-0.79	126	126
BMP2-4/NOG	-0.078	0.19	-9999	-0.56	63	63
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.15	0.22	-9999	-0.46	159	159

×

Glypican 2 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.086	0.15	-9999	-0.31	147	147
GPC2	-0.01	0.084	-9999	-0.31	34	34
GPC2/Midkine	-0.076	0.11	-9999	-0.4	12	12
neuron projection morphogenesis	-0.075	0.11	-9999	-0.4	12	12

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.043	0.11	-9999	-0.47	13	13
EGFR	0.006	0.076	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
USP6	0.011	0.026	-9999	-0.31	3	3
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.097	0.23	-9999	-0.63	72	72
ARRB2	-0.044	0.15	-9999	-0.45	59	59
mol:GTP	0.021	0.012	-9999	-10000	0	0
ARRB1	0.012	0.038	-9999	-0.82	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.01	0.054	-9999	-0.82	2	2
EGF	-0.11	0.29	-9999	-0.78	74	74
somatostatin receptor activity	0	0	-9999	-0.001	135	135
ARAP2	0.01	0.054	-9999	-0.82	2	2
mol:GDP	-0.12	0.15	-9999	-0.31	135	135
mol:PI-3-4-5-P3	0	0	-9999	-0.001	95	95
ITGA2B	-0.074	0.26	-9999	-0.82	50	50
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
ADAP1	0.013	0	-9999	-10000	0	0
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.17	0.24	-9999	-0.69	73	73
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.31	138	138
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.084	0.2	-9999	-0.55	72	72
ADRB2	-0.009	0.14	-9999	-0.82	13	13
receptor agonist activity	0	0	-9999	0	143	143
actin filament binding	0	0	-9999	-0.001	134	134
SRC	0.013	0.015	-9999	-0.31	1	1
ITGB3	-0.011	0.14	-9999	-0.82	14	14
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	131	131
ARF6/GDP	0.001	0.069	-9999	-0.34	2	2
ARF6/GDP/GULP/ACAP1	-0.19	0.2	-9999	-0.5	114	114
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.066	0.18	-9999	-0.54	59	59
ACAP1	0.001	0.075	-9999	-0.38	15	15
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.082	0.22	-9999	-0.68	59	59
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.11	0.3	-9999	-0.82	73	73
CYTH3	0.009	0.042	-9999	-0.64	2	2
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	121	121
endosomal lumen acidification	0	0	-9999	-0.001	139	139
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.32	-9999	-0.82	88	88
GNAQ/ARNO	0.009	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	39	39
MET	-0.11	0.16	-9999	-0.31	179	179
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.094	-9999	-0.33	37	37
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	132	132
GNA11	-0.002	0.11	-9999	-0.82	9	9
LHCGR	-0.099	0.27	-9999	-0.77	66	66
AGTR1	-0.32	0.41	-9999	-0.82	194	194
desensitization of G-protein coupled receptor protein signaling pathway	-0.082	0.22	-9999	-0.68	59	59
IPCEF1/ARNO	-0.056	0.16	-9999	-0.43	72	72
alphaIIb/beta3 Integrin	-0.083	0.23	-9999	-0.68	59	59

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.015	0.064	-10000	0	-0.36	13	13
SVIL	-0.007	0.031	-10000	0	-10000	0	0
ZNF318	0.061	0.093	-10000	0	-0.82	1	1
JMJD2C	-0.064	0.069	-10000	0	-0.12	273	273
T-DHT/AR/Ubc9	-0.28	0.3	-10000	0	-0.62	202	202
CARM1	0.012	0.003	-10000	0	-10000	0	0
PRDX1	0.015	0.004	-10000	0	-10000	0	0
PELP1	0.02	0.011	-10000	0	-10000	0	0
CTNNB1	-0.002	0.023	-10000	0	-10000	0	0
AKT1	0.026	0.02	-10000	0	-10000	0	0
PTK2B	0.004	0.015	-10000	0	-10000	0	0
MED1	0.025	0.019	-10000	0	-10000	0	0
MAK	0.052	0.13	-10000	0	-0.8	6	6
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.061	-10000	0	-0.82	2	2
GSN	-0.006	0.03	-10000	0	-10000	0	0
NCOA2	-0.065	0.24	-10000	0	-0.82	44	44
NCOA6	-0.007	0.047	-10000	0	-0.82	1	1
DNA-PK	0.059	0.084	0.26	1	-10000	0	1
NCOA4	0.011	0.004	-10000	0	-10000	0	0
PIAS3	-0.002	0.023	-10000	0	-10000	0	0
cell proliferation	-0.01	0.15	-10000	0	-1.1	6	6
XRCC5	0.025	0.018	-10000	0	-10000	0	0
UBE3A	-0.016	0.047	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.31	0.33	-10000	0	-0.67	209	209
FHL2	-0.16	0.37	-10000	0	-1.3	39	39
RANBP9	-0.005	0.029	-10000	0	-10000	0	0
JMJD1A	0.002	0.037	-10000	0	-0.12	37	37
CDK6	0.009	0.066	-10000	0	-0.82	3	3
TGFB1I1	-0.007	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.3	0.3	-10000	0	-0.63	205	205
XRCC6	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR	-0.33	0.32	-10000	0	-0.64	228	228
CTDSP1	0.009	0.006	-10000	0	-10000	0	0
CTDSP2	0.046	0.051	-10000	0	-10000	0	0
BRCA1	-0.007	0.031	-10000	0	-10000	0	0
TCF4	0.036	0.034	-10000	0	-10000	0	0
CDKN2A	-0.11	0.16	-10000	0	-0.31	140	140
SRF	0.028	0.04	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-1	6	6
KLK3	-0.44	0.71	-10000	0	-1.6	137	137
TMF1	0.006	0.054	-10000	0	-0.82	2	2
HNRNPA1	0.031	0.028	-10000	0	-10000	0	0
AOF2	-0.022	0.034	-10000	0	-0.075	137	137
APPL1	0.052	0.042	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.28	0.29	-10000	0	-0.61	202	202
AR	-0.38	0.42	-10000	0	-0.87	202	202
UBA3	0.009	0.006	-10000	0	-10000	0	0
PATZ1	0.031	0.028	-10000	0	-10000	0	0
PAWR	0.009	0.006	-10000	0	-10000	0	0
PRKDC	0.025	0.018	-10000	0	-10000	0	0
PA2G4	0.036	0.036	-10000	0	-10000	0	0
UBE2I	0.013	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.25	0.28	-10000	0	-0.57	202	202
RPS6KA3	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.28	0.3	-10000	0	-0.62	202	202
LATS2	0.03	0.048	-10000	0	-0.82	1	1
T-DHT/AR/PRX1	-0.24	0.28	-10000	0	-0.56	202	202
Cyclin D3/CDK11 p58	0	0.003	-10000	0	-10000	0	0
VAV3	-0.012	0.095	-10000	0	-0.83	6	6
KLK2	-0.77	0.63	-10000	0	-1.3	273	273
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.67	208	208
TMPRSS2	-0.19	0.32	-10000	0	-1.2	35	35
CCND1	0.001	0.049	-10000	0	-0.31	11	11
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.032	0.041	-10000	0	-0.082	162	162
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.036	0.077	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.28	0.3	-10000	0	-0.62	204	204
CMTM2	0.014	0.027	-10000	0	-0.31	3	3
SNURF	-0.032	0.19	-10000	0	-0.82	26	26
ZMIZ1	-0.013	0.051	-10000	0	-0.81	1	1
CCND3	0.014	0.002	-10000	0	-10000	0	0
TGIF1	0.031	0.028	-10000	0	-10000	0	0
FKBP4	-0.005	0.029	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.008	0.042	-9999	-0.31	8	8
CCL5	-0.044	0.2	-9999	-0.72	38	38
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.16	-9999	-0.48	50	50
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.092	0.16	-9999	-0.54	31	31
Syndecan-1/Syntenin	-0.092	0.16	-9999	-0.54	31	31
MAPK3	-0.069	0.14	-9999	-0.6	19	19
HGF/MET	-0.17	0.24	-9999	-0.69	73	73
TGFB1/TGF beta receptor Type II	0.008	0.042	-9999	-0.31	8	8
BSG	0.013	0.015	-9999	-0.31	1	1
keratinocyte migration	-0.091	0.15	-9999	-0.53	31	31
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.65	54	54
Syndecan-1/CD147	-0.081	0.15	-9999	-0.62	21	21
Syndecan-1/Syntenin/PIP2	-0.099	0.14	-9999	-0.55	28	28
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.097	0.14	-9999	-0.51	31	31
MMP7	-0.18	0.22	-9999	-0.37	240	240
HGF	-0.11	0.3	-9999	-0.82	73	73
Syndecan-1/CASK	-0.1	0.16	-9999	-0.46	50	50
Syndecan-1/HGF/MET	-0.2	0.24	-9999	-0.65	86	86
regulation of cell adhesion	-0.059	0.14	-9999	-0.58	19	19
HPSE	-0.017	0.14	-9999	-0.51	28	28
positive regulation of cell migration	-0.1	0.16	-9999	-0.48	50	50
SDC1	-0.11	0.16	-9999	-0.48	50	50
Syndecan-1/Collagen	-0.1	0.16	-9999	-0.48	50	50
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	179	179
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.57	79	79
MAPK1	-0.069	0.14	-9999	-0.6	19	19
homophilic cell adhesion	-0.1	0.16	-9999	-0.47	50	50
MMP1	-0.14	0.16	-9999	-0.31	229	229

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.18	0.42	-9999	-0.99	45	45
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.34	-9999	-0.83	103	103
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.18	0.42	-9999	-1	43	43
AP1	-0.29	0.45	-9999	-0.92	151	151
ABCG2	-0.19	0.42	-9999	-1	43	43
HIF1A	-0.008	0.067	-9999	-10000	0	0
TFF3	-0.57	0.51	-9999	-1.1	159	159
GATA2	0.014	0.015	-9999	-0.31	1	1
AKT1	-0.038	0.1	-9999	-10000	0	0
response to hypoxia	-0.059	0.11	-9999	-0.24	20	20
MCL1	-0.18	0.42	-9999	-0.99	44	44
NDRG1	-0.18	0.42	-9999	-0.99	44	44
SERPINE1	-0.2	0.43	-9999	-1	47	47
FECH	-0.18	0.42	-9999	-1	37	37
FURIN	-0.18	0.42	-9999	-1	43	43
NCOA2	-0.062	0.24	-9999	-0.82	44	44
EP300	-0.063	0.18	-9999	-0.34	105	105
HMOX1	-0.19	0.42	-9999	-1	45	45
BHLHE40	-0.19	0.42	-9999	-1	48	48
BHLHE41	-0.18	0.42	-9999	-0.98	50	50
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.017	0.036	-9999	-10000	0	0
ENG	0.042	0.092	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.82	109	109
RORA	-0.18	0.42	-9999	-1	44	44
ABCB1	-0.076	0.19	-9999	-1.4	8	8
TFRC	-0.18	0.42	-9999	-0.99	48	48
CXCR4	-0.18	0.42	-9999	-0.99	44	44
TF	-0.23	0.49	-9999	-1.1	70	70
CITED2	-0.22	0.47	-9999	-1.1	59	59
HIF1A/ARNT	-0.29	0.38	-9999	-1	66	66
LDHA	-0.039	0.05	-9999	-10000	0	0
ETS1	-0.18	0.42	-9999	-0.99	44	44
PGK1	-0.18	0.42	-9999	-1	40	40
NOS2	-0.2	0.43	-9999	-1	49	49
ITGB2	-0.19	0.42	-9999	-1	46	46
ALDOA	-0.18	0.42	-9999	-0.99	44	44
Cbp/p300/CITED2	-0.32	0.51	-9999	-1.1	101	101
FOS	-0.21	0.37	-9999	-0.82	128	128
HK2	-0.19	0.42	-9999	-1	40	40
SP1	0.022	0.008	-9999	-10000	0	0
GCK	-0.39	0.72	-9999	-1.5	135	135
HK1	-0.18	0.42	-9999	-0.99	44	44
NPM1	-0.18	0.42	-9999	-0.99	44	44
EGLN1	-0.18	0.42	-9999	-1	45	45
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.18	0.42	-9999	-0.98	47	47
SMAD3	0.015	0.003	-9999	-10000	0	0
EDN1	-0.16	0.32	-9999	-0.73	66	66
IGFBP1	-0.2	0.42	-9999	-1	46	46
VEGFA	-0.16	0.38	-9999	-0.77	68	68
HIF1A/JAB1	-0.011	0.02	-9999	-10000	0	0
CP	-0.35	0.55	-9999	-1.1	119	119
CXCL12	-0.23	0.48	-9999	-1.1	64	64
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.18	0.42	-9999	-1	37	37
EGLN3	-0.2	0.44	-9999	-1	49	49
CA9	-0.2	0.42	-9999	-1	45	45
TERT	-0.2	0.42	-9999	-1	44	44
ENO1	-0.18	0.42	-9999	-0.97	48	48
PFKL	-0.18	0.42	-9999	-1	43	43
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.22	0.44	-9999	-1	48	48
ARNT	-0.009	0.067	-9999	-10000	0	0
HNF4A	-0.026	0.065	-9999	-0.35	10	10
ADFP	-0.2	0.41	-9999	-0.93	61	61
SLC2A1	-0.15	0.38	-9999	-0.75	71	71
LEP	-0.2	0.42	-9999	-0.98	50	50
HIF1A/ARNT/Cbp/p300	-0.29	0.36	-9999	-0.86	104	104
EPO	-0.14	0.33	-9999	-0.95	25	25
CREBBP	-0.063	0.18	-9999	-0.34	107	107
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.82	101	101
PFKFB3	-0.18	0.42	-9999	-1	43	43
NT5E	-0.19	0.43	-9999	-1.1	40	40

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.089	0.21	-10000	0	-0.56	76	76
cell-cell adhesion	0.15	0.19	0.55	10	-10000	0	10
Ephrin B/EPHB2/RasGAP	-0.014	0.069	-10000	0	-0.46	10	10
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.081	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.22	0.27	-10000	0	-0.56	187	187
HRAS/GDP	-0.14	0.17	-10000	0	-0.5	12	12
Ephrin B/EPHB1/GRB7	-0.21	0.25	-10000	0	-0.51	192	192
Endophilin/SYNJ1	0.025	0.072	-10000	0	-0.43	10	10
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.19	0.23	-10000	0	-0.48	192	192
endothelial cell migration	-0.003	0.037	-10000	0	-0.47	3	3
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.034	0.073	-10000	0	-0.43	10	10
HRAS	0.012	0.021	-10000	0	-0.31	2	2
RRAS	0.025	0.074	-10000	0	-0.44	10	10
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.16	0.24	-10000	0	-0.45	192	192
lamellipodium assembly	-0.15	0.19	-10000	0	-0.55	10	10
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.11	0.18	-10000	0	-0.44	10	10
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.066	-10000	0	-0.82	3	3
EPHB3	-0.19	0.16	-10000	0	-0.31	294	294
EPHB1	-0.31	0.41	-10000	0	-0.82	187	187
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.071	0.18	-10000	0	-0.46	11	11
Ephrin B/EPHB2	-0.014	0.07	-10000	0	-0.47	10	10
Ephrin B/EPHB3	-0.086	0.087	-10000	0	-0.57	7	7
JNK cascade	-0.15	0.24	-10000	0	-0.46	189	189
Ephrin B/EPHB1	-0.19	0.24	-10000	0	-0.48	192	192
RAP1/GDP	-0.055	0.16	-10000	0	-0.53	3	3
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.01	0.12	-10000	0	-0.46	24	24
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.25	-10000	0	-0.51	189	189
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.16	0.19	-10000	0	-0.52	17	17
Rap1/GTP	-0.15	0.19	-10000	0	-0.56	10	10
axon guidance	-0.088	0.2	-10000	0	-0.56	76	76
MAPK3	-0.08	0.16	-10000	0	-0.53	2	2
MAPK1	-0.08	0.16	-10000	0	-0.53	2	2
Rac1/GDP	-0.046	0.17	-10000	0	-0.46	7	7
actin cytoskeleton reorganization	-0.11	0.13	-10000	0	-0.46	6	6
CDC42/GDP	-0.046	0.17	-10000	0	-0.46	7	7
PI3K	-0.003	0.037	-10000	0	-0.47	3	3
EFNA5	-0.12	0.3	-10000	0	-0.82	75	75
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.055	-10000	0	-0.33	10	10
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.15	0.18	-10000	0	-0.54	11	11
PTK2	0.042	0.052	-10000	0	-10000	0	0
MAP4K4	-0.16	0.25	-10000	0	-0.46	189	189
SRC	0.013	0.015	-10000	0	-0.31	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.071	0.18	-10000	0	-0.55	3	3
MAP2K1	-0.092	0.17	-10000	0	-0.41	10	10
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.2	0.24	-10000	0	-0.5	189	189
cell migration	-0.089	0.19	-10000	0	-0.44	10	10
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.026	0.073	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.021	0.17	-10000	0	-0.45	60	60
HRAS/GTP	-0.17	0.2	-10000	0	-0.41	194	194
Ephrin B1/EPHB1-2	-0.2	0.25	-10000	0	-0.51	189	189
cell adhesion mediated by integrin	0.013	0.076	0.5	7	-10000	0	7
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.18	0.22	-10000	0	-0.44	194	194
RAC1-CDC42/GTP	-0.21	0.21	-10000	0	-0.49	145	145
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.055	0.16	-10000	0	-0.53	3	3
ruffle organization	-0.12	0.22	-10000	0	-0.57	10	10
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.017	0.12	-10000	0	-0.46	24	24
Ephrin B/EPHB2/KALRN	-0.014	0.069	-10000	0	-0.46	10	10
ROCK1	-0.074	0.081	-10000	0	-10000	0	0
RAS family/GDP	-0.085	0.11	-10000	0	-0.52	3	3
Rac1/GTP	-0.16	0.2	-10000	0	-0.6	10	10
Ephrin B/EPHB1/Src/Paxillin	-0.11	0.18	-10000	0	-0.34	192	192

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.11	0.39	-9999	-1.3	43	43
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.036	0.11	-9999	-0.39	19	19
ATF2/c-Jun	-0.22	0.42	-9999	-0.97	110	110
MAPK11	-0.036	0.11	-9999	-0.39	19	19
MITF	-0.029	0.13	-9999	-0.4	43	43
MAPKAPK5	-0.029	0.13	-9999	-0.48	19	19
KRT8	-0.029	0.13	-9999	-0.4	43	43
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.049	0.17	-9999	-0.52	43	43
CEBPB	-0.029	0.13	-9999	-0.4	43	43
SLC9A1	-0.029	0.13	-9999	-0.4	43	43
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.071	0.19	-9999	-0.44	67	67
p38alpha-beta/MNK1	-0.025	0.14	-9999	-0.5	19	19
JUN	-0.22	0.42	-9999	-0.95	112	112
PPARGC1A	-0.23	0.25	-9999	-0.46	252	252
USF1	-0.029	0.13	-9999	-0.48	19	19
RAB5/GDP/GDI1	-0.038	0.084	-9999	-0.35	19	19
NOS2	-0.049	0.16	-9999	-0.66	8	8
DDIT3	-0.031	0.14	-9999	-0.41	43	43
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.013	0.11	-9999	-0.39	18	18
p38alpha-beta/HBP1	-0.025	0.14	-9999	-0.5	19	19
CREB1	-0.049	0.16	-9999	-0.46	43	43
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.015	0.12	-9999	-0.44	18	18
RPS6KA4	-0.029	0.13	-9999	-0.4	43	43
PLA2G4A	-0.049	0.2	-9999	-0.61	44	44
GDI1	-0.029	0.13	-9999	-0.4	43	43
TP53	-0.038	0.16	-9999	-0.5	43	43
RPS6KA5	-0.077	0.2	-9999	-0.47	86	86
ESR1	-0.065	0.21	-9999	-0.54	57	57
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.03	0.14	-9999	-0.4	44	44
MEF2A	-0.03	0.14	-9999	-0.4	44	44
EIF4EBP1	-0.049	0.16	-9999	-0.45	44	44
KRT19	-0.1	0.21	-9999	-0.54	58	58
ELK4	-0.029	0.13	-9999	-0.4	43	43
ATF6	-0.029	0.13	-9999	-0.4	43	43
ATF1	-0.05	0.16	-9999	-0.47	44	44
p38alpha-beta/MAPKAPK2	-0.025	0.14	-9999	-0.5	19	19
p38alpha-beta/MAPKAPK3	-0.025	0.14	-9999	-0.5	19	19

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.022	0.16	-10000	0	-0.43	32	32
TBX21	-0.11	0.44	-10000	0	-1.1	59	59
B2M	0.012	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.02	-10000	0	-10000	0	0
IL12RB1	-0.018	0.12	-10000	0	-0.37	44	44
GADD45B	-0.089	0.38	-10000	0	-0.96	56	56
IL12RB2	-0.016	0.16	-10000	0	-0.73	21	21
GADD45G	-0.072	0.34	-10000	0	-0.92	45	45
natural killer cell activation	0.003	0.022	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	-0.035	0.16	-10000	0	-0.41	58	58
IL2RA	-0.047	0.2	-10000	0	-0.58	49	49
IFNG	-0.11	0.28	-10000	0	-0.72	78	78
STAT3 (dimer)	-0.07	0.32	-10000	0	-0.76	61	61
HLA-DRB5	-0.041	0.13	-10000	0	-0.35	69	69
FASLG	-0.13	0.47	-10000	0	-1.2	61	61
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.89	63	63
CD4	0.001	0.057	-10000	0	-0.33	5	5
SOCS1	0.009	0.048	-10000	0	-0.42	5	5
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.099	0.27	-10000	0	-0.72	72	72
CD3E	-0.074	0.25	-10000	0	-0.75	53	53
CD3G	-0.15	0.33	-10000	0	-0.8	96	96
IL12Rbeta2/JAK2	-0.001	0.13	-10000	0	-0.64	18	18
CCL3	-0.1	0.43	-10000	0	-1.2	49	49
CCL4	-0.15	0.52	-10000	0	-1.3	64	64
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
IL18/IL18R	-0.031	0.2	-10000	0	-0.57	45	45
NOS2	-0.085	0.34	-10000	0	-0.89	48	48
IL12/IL12R/TYK2/JAK2/SPHK2	-0.02	0.15	-10000	0	-0.4	34	34
IL1R1	-0.084	0.37	-10000	0	-0.98	49	49
IL4	0.001	0.022	-10000	0	-10000	0	0
JAK2	0.014	0.044	-10000	0	-0.86	1	1
EntrezGene:6957	-0.006	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.56	-10000	0	-1.2	103	103
RAB7A	-0.038	0.29	-10000	0	-0.73	37	37
lysosomal transport	-0.034	0.28	-10000	0	-0.68	39	39
FOS	-0.41	0.65	-10000	0	-1.3	161	161
STAT4 (dimer)	-0.075	0.35	-10000	0	-0.84	58	58
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.92	81	81
GZMA	-0.1	0.41	-10000	0	-1.1	52	52
GZMB	-0.098	0.39	-10000	0	-1.1	45	45
HLX	0.004	0.055	-10000	0	-0.31	14	14
LCK	-0.11	0.43	-10000	0	-1	65	65
TCR/CD3/MHC II/CD4	-0.19	0.35	-10000	0	-0.62	134	134
IL2/IL2R	-0.081	0.22	-10000	0	-0.67	47	47
MAPK14	-0.067	0.35	-10000	0	-0.82	60	60
CCR5	-0.095	0.4	-10000	0	-1.1	44	44
IL1B	-0.054	0.24	-10000	0	-0.79	43	43
STAT6	-0.003	0.11	-10000	0	-0.25	23	23
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.049	-10000	0	-0.31	11	11
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.001	0.096	-10000	0	-0.56	11	11
CD8A	-0.05	0.22	-10000	0	-0.83	36	36
CD8B	-0.092	0.27	-10000	0	-0.73	68	68
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.022	0.16	0.43	32	-10000	0	32
IL2RB	-0.015	0.13	-10000	0	-0.51	26	26
proteasomal ubiquitin-dependent protein catabolic process	-0.063	0.32	-10000	0	-0.76	58	58
IL2RG	-0.047	0.19	-10000	0	-0.55	52	52
IL12	-0.056	0.22	-10000	0	-0.64	55	55
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.027	0.16	-10000	0	-0.64	27	27
IL2	0.004	0.006	-10000	0	-10000	0	0
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.074	0.26	-10000	0	-0.8	53	53
IL12/IL12R/TYK2/JAK2	-0.12	0.48	-10000	0	-1.1	66	66
MAP2K3	-0.068	0.35	-10000	0	-0.81	60	60
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.075	0.36	-10000	0	-0.83	62	62
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.027	0.13	-10000	0	-0.4	44	44
IL18RAP	-0.022	0.17	-10000	0	-0.8	22	22
IL12Rbeta1/TYK2	-0.003	0.093	-10000	0	-0.64	4	4
EOMES	-0.15	0.43	-10000	0	-1.5	43	43
STAT1 (dimer)	-0.13	0.37	-10000	0	-0.79	88	88
T cell proliferation	-0.047	0.27	-10000	0	-0.62	53	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.027	0.15	-10000	0	-0.42	47	47
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.24	-10000	0	-0.69	59	59
ATF2	-0.069	0.33	-10000	0	-0.75	61	61

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.002	0.047	-9999	-1	1	1
forebrain development	-0.32	0.29	-9999	-0.56	254	254
GNAO1	-0.02	0.15	-9999	-0.72	20	20
SMO/beta Arrestin2	0.011	0.032	-9999	-0.63	1	1
SMO	0.006	0.039	-9999	-0.82	1	1
ARRB2	0.008	0.007	-9999	-10000	0	0
GLI3/SPOP	0.044	0.057	-9999	-10000	0	0
mol:GTP	-0.002	0.003	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.01	0.006	-9999	-10000	0	0
SIN3/HDAC complex	0.009	0.03	-9999	-0.5	1	1
GNAI1	0.008	0.039	-9999	-0.84	1	1
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.24	0.19	-9999	-0.51	134	134
SAP30	0.012	0.038	-9999	-0.82	1	1
mol:GDP	0.006	0.039	-9999	-0.82	1	1
MIM/GLI2A	-0.007	0.043	-9999	-0.31	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GLI2	0.033	0.062	-9999	-10000	0	0
GLI3	0.039	0.059	-9999	-10000	0	0
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.012	0.038	-9999	-0.82	1	1
Gi family/GTP	0.007	0.071	-9999	-0.33	18	18
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.029	0.05	-9999	-10000	0	0
GLI2/Su(fu)	0.022	0.059	-9999	-10000	0	0
FOXA2	-0.66	0.66	-9999	-1.3	234	234
neural tube patterning	-0.32	0.29	-9999	-0.56	254	254
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.022	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	-0.007	0.043	-9999	-0.31	1	1
embryonic limb morphogenesis	-0.32	0.29	-9999	-0.56	254	254
SUFU	0.016	0.021	-9999	-0.28	1	1
LGALS3	-0.1	0.16	-9999	-0.31	171	171
catabolic process	0.061	0.069	-9999	-0.39	2	2
GLI3A/CBP	-0.2	0.2	-9999	-0.38	253	253
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.33	0.29	-9999	-0.57	254	254
RAB23	0.006	0.076	-9999	-0.82	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.035	0.079	-9999	-0.4	1	1
GNAZ	0.01	0.006	-9999	-10000	0	0
RBBP4	0.009	0.066	-9999	-0.82	3	3
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.058	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.013	0.063	-9999	-0.42	2	2
PTCH1	-0.28	0.27	-9999	-0.62	134	134
MIM/GLI1	-0.45	0.39	-9999	-0.75	252	252
CREBBP	-0.2	0.2	-9999	-0.38	253	253
Su(fu)/SIN3/HDAC complex	0.056	0.027	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.082	0.063	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.18	-9999	-0.65	40	40
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.61	69	69
Syndecan-4/ADAM12	-0.17	0.18	-9999	-0.65	41	41
CCL5	-0.044	0.2	-9999	-0.72	38	38
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
PLG	0	0.034	-9999	-0.31	4	4
ADAM12	-0.067	0.14	-9999	-0.31	119	119
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.064	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.17	0.21	-9999	-0.68	49	49
Syndecan-4/CXCL12/CXCR4	-0.17	0.23	-9999	-0.66	69	69
Syndecan-4/Laminin alpha3	-0.15	0.19	-9999	-0.66	45	45
MDK	-0.086	0.15	-9999	-0.31	147	147
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.64	42	42
Syndecan-4/Midkine	-0.18	0.19	-9999	-0.65	41	41
FZD7	0.006	0.076	-9999	-0.82	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.6	41	41
THBS1	-0.011	0.086	-9999	-0.31	36	36
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.66	40	40
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.61	69	69
Syndecan-4/TACI	-0.24	0.26	-9999	-0.64	119	119
CXCR4	0.012	0.021	-9999	-0.31	2	2
cell adhesion	-0.072	0.091	-9999	-0.45	22	22
Syndecan-4/Dynamin	-0.13	0.18	-9999	-0.65	40	40
Syndecan-4/TSP1	-0.14	0.18	-9999	-0.65	40	40
Syndecan-4/GIPC	-0.13	0.18	-9999	-0.65	40	40
Syndecan-4/RANTES	-0.16	0.22	-9999	-0.74	48	48
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.05	0.22	-9999	-0.81	37	37
LAMA3	-0.026	0.16	-9999	-0.59	31	31
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.016	0.17	-9999	-0.75	22	22
Syndecan-4/alpha-Actinin	-0.13	0.18	-9999	-0.65	40	40
TFPI	-0.035	0.2	-9999	-0.82	28	28
F2	-0.006	0.05	-9999	-0.31	12	12
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.17	0.21	-9999	-0.67	54	54
ACTN1	0.013	0.015	-9999	-0.31	1	1
TNC	-0.11	0.17	-9999	-0.32	182	182
Syndecan-4/CXCL12	-0.18	0.24	-9999	-0.68	69	69
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.075	0.26	-9999	-0.82	51	51
TNFRSF13B	-0.19	0.35	-9999	-0.79	120	120
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.012	0.038	-9999	-0.82	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.66	40	40
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.32	302	302
cell migration	-0.021	0.017	-9999	-10000	0	0
PRKCD	0.008	0.015	-9999	-10000	0	0
vasculogenesis	-0.14	0.17	-9999	-0.62	40	40
SDC4	-0.15	0.19	-9999	-0.7	40	40
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.7	40	40
Syndecan-4/PI-4-5-P2/PKC alpha	-0.051	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.18	-9999	-0.65	40	40
MMP9	-0.085	0.24	-9999	-0.57	79	79
Rac1/GTP	-0.073	0.094	-9999	-0.46	22	22
cytoskeleton organization	-0.13	0.17	-9999	-0.62	40	40
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.21	-9999	-0.65	58	58

×

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	-0.057	0.21	-10000	0	-0.69	17	17
CRP	-0.063	0.22	-10000	0	-0.71	17	17
cell cycle arrest	-0.08	0.24	-10000	0	-0.73	32	32
TIMP1	-0.16	0.22	-10000	0	-0.59	42	42
IL6ST	-0.11	0.29	-10000	0	-0.82	68	68
Rac1/GDP	-0.088	0.25	-10000	0	-0.62	59	59
AP1	-0.19	0.32	-10000	0	-0.71	118	118
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.099	0.23	-10000	0	-0.68	21	21
HSP90B1	0.022	0.043	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
MAPK14	-0.099	0.3	-10000	0	-0.81	55	55
AKT1	0.053	0.057	-10000	0	-1.1	1	1
FOXO1	0.059	0.053	-10000	0	-0.98	1	1
MAP2K6	-0.1	0.29	-10000	0	-0.72	62	62
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.076	0.24	-10000	0	-0.66	43	43
MITF	-0.09	0.26	-10000	0	-0.63	59	59
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.013	0	-10000	0	-10000	0	0
A2M	0.025	0.006	-10000	0	-10000	0	0
CEBPB	0.022	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.023	0.086	-10000	0	-0.49	1	1
STAT3	-0.093	0.25	-10000	0	-0.79	32	32
STAT1	-0.011	0.023	-10000	0	-10000	0	0
CEBPD	-0.057	0.21	-10000	0	-0.69	17	17
PIK3CA	0.01	0.066	-10000	0	-0.82	3	3
PI3K	0.019	0.051	-10000	0	-0.63	3	3
JUN	-0.18	0.35	-10000	0	-0.82	109	109
PIAS3/MITF	-0.078	0.25	-10000	0	-0.63	52	52
MAPK11	-0.099	0.3	-10000	0	-0.81	55	55
STAT3 (dimer)/FOXO1	-0.008	0.2	-10000	0	-0.6	18	18
GRB2/SOS1/GAB family	-0.11	0.2	-10000	0	-0.7	31	31
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.26	-10000	0	-0.56	81	81
GRB2	0.014	0	-10000	0	-10000	0	0
JAK2	0.012	0.038	-10000	0	-0.82	1	1
LBP	-0.061	0.2	-10000	0	-0.63	12	12
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.014	0.005	-10000	0	-10000	0	0
MYC	-0.073	0.27	-10000	0	-0.94	24	24
FGG	-0.067	0.22	-10000	0	-0.7	19	19
macrophage differentiation	-0.08	0.24	-10000	0	-0.73	32	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.18	0.29	-10000	0	-0.56	152	152
JUNB	-0.063	0.23	-10000	0	-0.71	30	30
FOS	-0.21	0.37	-10000	0	-0.82	128	128
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.1	0.28	-10000	0	-0.52	105	105
STAT1/PIAS1	-0.083	0.24	-10000	0	-0.54	67	67
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.062	-10000	0	-1.2	1	1
STAT3 (dimer)	-0.09	0.24	-10000	0	-0.76	32	32
PRKCD	-0.064	0.23	-10000	0	-0.66	35	35
IL6R	-0.014	0.15	-10000	0	-0.82	16	16
SOCS3	-0.12	0.37	-10000	0	-1.1	52	52
gp130 (dimer)/JAK1/JAK1/LMO4	-0.058	0.2	-10000	0	-0.55	68	68
Rac1/GTP	-0.11	0.24	-10000	0	-0.62	58	58
HCK	-0.008	0.08	-10000	0	-0.31	31	31
MAPKKK cascade	0.009	0.077	-10000	0	-0.98	1	1
bone resorption	-0.095	0.22	-10000	0	-0.65	21	21
IRF1	-0.057	0.21	-10000	0	-0.7	16	16
mol:GDP	-0.1	0.26	-10000	0	-0.6	71	71
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.1	0.27	-10000	0	-0.62	71	71
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.3	-10000	0	-0.8	56	56
PTPN11	-0.011	0.059	-10000	0	-1.2	1	1
IL6/IL6RA	-0.15	0.29	-10000	0	-0.66	107	107
gp130 (dimer)/TYK2/TYK2/LMO4	-0.064	0.2	-10000	0	-0.55	68	68
gp130 (dimer)/JAK2/JAK2/LMO4	-0.065	0.2	-10000	0	-0.55	68	68
IL6	-0.17	0.34	-10000	0	-0.72	123	123
PIAS3	0.013	0	-10000	0	-10000	0	0
PTPRE	-0.083	0.15	-10000	0	-0.32	137	137
PIAS1	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.1	0.26	-10000	0	-0.46	136	136
LMO4	0.012	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.11	0.23	0.38	1	-0.79	31	32
MCL1	0.059	0.049	-10000	0	-0.88	1	1

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.095	0.22	-9999	-0.41	145	145
MAP3K8	-0.003	0.11	-9999	-0.83	8	8
FOS	-0.058	0.17	-9999	-0.5	35	35
PRKCA	-0.027	0.18	-9999	-0.83	22	22
PTPN7	-0.045	0.17	-9999	-0.46	57	57
HRAS	0.011	0.021	-9999	-0.31	2	2
PRKCB	-0.03	0.13	-9999	-0.36	52	52
NRAS	0.013	0.002	-9999	-10000	0	0
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.031	0.12	-9999	-0.52	17	17
MAP2K1	-0.025	0.15	-9999	-0.56	29	29
ELK1	0.008	0.011	-9999	-10000	0	0
BRAF	-0.045	0.13	-9999	-0.58	26	26
mol:GTP	-0.001	0.003	-9999	-0.006	127	127
MAPK1	-0.031	0.12	-9999	-0.42	28	28
RAF1	-0.045	0.13	-9999	-0.58	26	26
KRAS	0.013	0.002	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.021	-9999	-0.31	2	2
EGFR	0.006	0.076	-9999	-0.82	4	4
EGF/EGFR	-0.076	0.17	-9999	-0.46	78	78
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.071	0.16	-9999	-0.46	72	72
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.01	0.046	-9999	-0.44	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
EGF/EGFR dimer/SHC	-0.084	0.2	-9999	-0.55	72	72
mol:GDP	-0.07	0.16	-9999	-0.46	72	72
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.003	0.087	-9999	-0.68	7	7
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.065	0.15	-9999	-0.42	72	72
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.066	0.15	-9999	-0.43	72	72
FRAP1	-0.034	0.17	-9999	-0.44	72	72
EGF/EGFR dimer	-0.097	0.22	-9999	-0.63	72	72
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.01	0.073	-9999	-0.63	6	6

×

Thromboxane A2 receptor signaling

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
TGM2	-0.034	0.11	-10000	0	-0.31	67	67
GNB1/GNG2	-0.044	0.068	-10000	0	-0.2	46	46
AKT1	-0.013	0.1	-10000	0	-0.21	38	38
EGF	-0.11	0.29	-10000	0	-0.78	74	74
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.031	0.077	-10000	0	-0.65	2	2
mol:Ca2+	-0.043	0.15	-10000	0	-0.31	73	73
LYN	0.032	0.076	-10000	0	-0.65	2	2
RhoA/GTP	-0.031	0.045	-10000	0	-0.14	2	2
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.043	0.16	-10000	0	-0.35	71	71
GNG2	0.012	0.038	-10000	0	-0.82	1	1
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.026	0.12	-10000	0	-0.54	11	11
G beta5/gamma2	-0.06	0.092	-10000	0	-0.27	46	46
PRKCH	-0.051	0.16	-10000	0	-0.36	70	70
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
TXA2/TP beta/beta Arrestin3	-0.013	0.055	-10000	0	-0.3	16	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.023	0.17	-10000	0	-0.82	21	21
G12 family/GTP	-0.077	0.11	-10000	0	-0.31	71	71
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.013	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.1	0.36	15	-10000	0	15
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.21	0.37	-10000	0	-0.82	131	131
mol:IP3	-0.059	0.18	-10000	0	-0.39	73	73
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.087	0.23	-10000	0	-0.53	71	71
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.098	0.2	-10000	0	-0.4	142	142
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.024	0.081	-10000	0	-0.65	2	2
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.003	0.093	-10000	0	-0.82	6	6
PRKCB1	-0.059	0.17	-10000	0	-0.39	73	73
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.084	0.23	-10000	0	-0.54	75	75
LCK	0.022	0.097	-10000	0	-0.55	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.019	0.09	-10000	0	-0.97	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.031	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.019	0.089	-10000	0	-0.96	2	2
MAPK14	-0.019	0.11	-10000	0	-0.24	38	38
TGM2/GTP	-0.072	0.2	-10000	0	-0.44	72	72
MAPK11	-0.019	0.11	-10000	0	-0.23	44	44
ARHGEF1	-0.015	0.089	-10000	0	-0.19	23	23
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.056	0.18	-10000	0	-0.39	75	75
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.051	0.15	-10000	0	-0.3	80	80
cAMP biosynthetic process	-0.058	0.17	-10000	0	-0.36	72	72
Gq family/GTP/EBP50	-0.043	0.12	-10000	0	-0.35	21	21
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.032	0.076	-10000	0	-0.65	2	2
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.018	0.1	-10000	0	-0.31	16	16
VCAM1	-0.037	0.14	-10000	0	-0.3	74	74
TP beta/Gq family/GDP/G beta5/gamma2	-0.026	0.12	-10000	0	-0.54	11	11
platelet activation	-0.025	0.15	-10000	0	-0.3	70	70
PGI2/IP	-0.008	0.071	-10000	0	-0.64	6	6
PRKACA	-0.001	0.11	-10000	0	-0.43	25	25
Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.5	11	11
TXA2/TP beta/beta Arrestin2	-0.024	0.12	-10000	0	-0.66	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.006	0.11	-10000	0	-0.42	25	25
mol:DAG	-0.067	0.19	-10000	0	-0.44	73	73
EGFR	0.006	0.076	-10000	0	-0.82	4	4
TXA2/TP alpha	-0.081	0.22	-10000	0	-0.5	72	72
Gq family/GTP	-0.076	0.13	-10000	0	-0.3	119	119
YES1	0.032	0.076	-10000	0	-0.65	2	2
GNAI2/GTP	-0.017	0.078	-10000	0	-0.8	2	2
PGD2/DP	-0.028	0.13	-10000	0	-0.64	21	21
SLC9A3R1	0.012	0.021	-10000	0	-0.31	2	2
FYN	0.032	0.076	-10000	0	-0.65	2	2
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.013	0.094	-10000	0	-0.33	37	37
PGK/cGMP	-0.15	0.25	-10000	0	-0.56	131	131
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.032	0.1	-10000	0	-0.66	6	6
NOS3	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.063	0.18	-10000	0	-0.4	77	77
PRKCB	-0.061	0.17	-10000	0	-0.38	75	75
PRKCE	-0.053	0.17	-10000	0	-0.38	71	71
PRKCD	-0.054	0.17	-10000	0	-0.39	71	71
PRKCG	-0.058	0.18	-10000	0	-0.4	70	70
muscle contraction	-0.073	0.22	-10000	0	-0.5	73	73
PRKCZ	-0.043	0.16	-10000	0	-0.35	71	71
ARR3	0.004	0.006	-10000	0	-10000	0	0
TXA2/TP beta	-0.019	0.091	-10000	0	-0.98	2	2
PRKCQ	-0.052	0.17	-10000	0	-0.37	74	74
MAPKKK cascade	-0.074	0.2	-10000	0	-0.47	74	74
SELE	-0.057	0.18	-10000	0	-0.43	72	72
TP beta/GNAI2/GDP/G beta/gamma	-0.019	0.094	-10000	0	-1.1	2	2
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.35	-10000	0	-0.82	112	112
chemotaxis	-0.096	0.26	-10000	0	-0.62	74	74
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	-0.002	0.11	-10000	0	-0.82	9	9
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.033	0.14	-9999	-0.46	37	37
NF kappa B1 p50/RelA/I kappa B alpha	-0.055	0.11	-9999	-0.54	7	7
alphaV/beta3 Integrin/Osteopontin/Src	-0.067	0.15	-9999	-0.62	24	24
AP1	-0.26	0.35	-9999	-0.84	112	112
ILK	-0.032	0.15	-9999	-0.49	37	37
bone resorption	-0.047	0.15	-9999	-0.56	18	18
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.052	0.12	-9999	-0.45	37	37
ITGAV	0.01	0.054	-9999	-0.82	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.028	0.13	-9999	-0.63	21	21
alphaV/beta3 Integrin/Osteopontin	-0.07	0.15	-9999	-0.56	37	37
MAP3K1	-0.033	0.15	-9999	-0.5	37	37
JUN	-0.18	0.35	-9999	-0.82	109	109
MAPK3	-0.033	0.15	-9999	-0.46	37	37
MAPK1	-0.033	0.15	-9999	-0.46	37	37
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.031	0.17	-9999	-0.51	42	42
ITGB3	-0.01	0.14	-9999	-0.82	14	14
NFKBIA	-0.026	0.15	-9999	-0.45	37	37
FOS	-0.21	0.37	-9999	-0.82	128	128
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.11	0.17	-9999	-0.7	4	4
NF kappa B1 p50/RelA	-0.061	0.11	-9999	-0.55	5	5
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.02	0.12	-9999	-0.66	15	15
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.033	0.15	-9999	-0.5	37	37
VAV3	-0.027	0.16	-9999	-0.48	42	42
MAP3K14	-0.04	0.15	-9999	-0.5	37	37
ROCK2	-0.023	0.17	-9999	-0.82	21	21
SPP1	-0.083	0.2	-9999	-0.42	108	108
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.055	0.13	-9999	-0.53	11	11
MMP2	-0.18	0.29	-9999	-0.65	108	108

×

amb2 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
alphaM/beta2 Integrin/proMMP-2	-0.043	0.12	-9999	-0.54	18	18
alphaM/beta2 Integrin/GPIbA	-0.054	0.14	-9999	-0.51	35	35
alphaM/beta2 Integrin/proMMP-9	-0.093	0.2	-9999	-0.58	56	56
PLAUR	-0.088	0.15	-9999	-0.31	150	150
HMGB1	0.002	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.034	0.099	-9999	-0.52	11	11
AGER	-0.06	0.22	-9999	-0.8	37	37
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.007	0.079	-9999	-0.31	30	30
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.12	0.19	-9999	-0.62	44	44
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.57	79	79
CYR61	-0.24	0.38	-9999	-0.82	146	146
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.072	0.091	-9999	-0.44	9	9
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.003	0.11	-9999	-0.59	13	13
MYH2	-0.1	0.12	-9999	-0.4	36	36
MST1R	0.001	0.096	-9999	-0.65	9	9
leukocyte activation during inflammatory response	-0.039	0.093	-9999	-0.46	10	10
APOB	-0.01	0.078	-9999	-0.31	30	30
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.001	0.1	-9999	-0.82	7	7
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	-0.019	0.15	-9999	-0.63	24	24
alphaM/beta2 Integrin/CTGF	-0.12	0.22	-9999	-0.57	88	88
alphaM/beta2 Integrin	-0.095	0.11	-9999	-0.35	46	46
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.082	0.15	-9999	-0.31	141	141
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.094	0.11	-9999	-0.35	46	46
cell adhesion	-0.054	0.14	-9999	-0.51	35	35
NFKB1	-0.13	0.3	-9999	-0.74	59	59
THY1	0.011	0.03	-9999	-0.31	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.014	0.049	-9999	-0.34	2	2
alphaM/beta2 Integrin/LRP/tPA	-0.035	0.1	-9999	-0.58	10	10
IL6	-0.24	0.46	-9999	-1.1	104	104
ITGB2	-0.018	0.086	-9999	-0.34	28	28
elevation of cytosolic calcium ion concentration	-0.14	0.16	-9999	-0.53	34	34
alphaM/beta2 Integrin/JAM2/JAM3	-0.032	0.1	-9999	-0.6	9	9
JAM2	0.006	0.077	-9999	-0.72	5	5
alphaM/beta2 Integrin/ICAM1	-0.068	0.13	-9999	-0.5	22	22
alphaM/beta2 Integrin/uPA/Plg	-0.098	0.12	-9999	-0.52	19	19
RhoA/GTP	-0.11	0.12	-9999	-0.42	39	39
positive regulation of phagocytosis	-0.07	0.12	-9999	-0.48	17	17
Ron/MSP	-0.011	0.078	-9999	-0.63	7	7
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.16	-9999	-0.54	34	34
alphaM/beta2 Integrin/uPAR	-0.084	0.13	-9999	-0.45	35	35
PLAU	-0.14	0.16	-9999	-10000	0	0
PLAT	0.001	0.086	-9999	-0.48	12	12
actin filament polymerization	-0.099	0.11	-9999	-0.38	36	36
MST1	0.011	0.041	-9999	-0.57	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.04	0.094	-9999	-0.51	8	8
TNF	-0.18	0.4	-9999	-1	75	75
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.13	-9999	-0.54	21	21
fibrinolysis	-0.098	0.12	-9999	-0.51	19	19
HCK	-0.008	0.08	-9999	-0.31	31	31
dendritic cell antigen processing and presentation	-0.094	0.11	-9999	-0.35	46	46
VTN	-0.07	0.24	-9999	-0.76	52	52
alphaM/beta2 Integrin/CYR61	-0.2	0.28	-9999	-0.58	160	160
LPA	-0.002	0.043	-9999	-0.31	9	9
LRP1	0.012	0.038	-9999	-0.82	1	1
cell migration	-0.089	0.2	-9999	-0.57	57	57
FN1	-0.22	0.15	-9999	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.035	0.1	-9999	-0.52	11	11
MPO	0.001	0.088	-9999	-0.63	8	8
KNG1	-0.014	0.077	-9999	-0.31	30	30
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.094	0.12	-9999	-0.46	15	15
ELA2	0	0	-9999	-10000	0	0
PLG	-0.003	0.035	-9999	-0.31	6	6
CTGF	-0.11	0.3	-9999	-0.82	71	71
alphaM/beta2 Integrin/Hck	-0.045	0.12	-9999	-0.56	19	19
ITGAM	-0.023	0.11	-9999	-0.39	30	30
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.046	0.13	-9999	-0.52	26	26
HP	-0.081	0.16	-9999	-0.34	129	129
leukocyte adhesion	-0.092	0.16	-9999	-0.61	26	26
SELP	-0.003	0.11	-9999	-0.59	13	13

×

TCGA08_p53

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.084	0.11	-9999	-0.21	206	206
TP53	-0.028	0.033	-9999	-10000	0	0
Senescence	-0.028	0.033	-9999	-10000	0	0
Apoptosis	-0.028	0.033	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.053	0.062	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.025	0.077	0.29	35	-10000	0	35
RFC1	0.025	0.077	0.29	35	-10000	0	35
PRKDC	0.025	0.077	0.29	35	-10000	0	35
RIPK1	0.014	0.004	-10000	0	-10000	0	0
CASP7	-0.013	0.045	0.2	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.028	0.1	0.26	4	-0.37	31	35
MAP2K4	-0.023	0.16	-10000	0	-0.4	34	34
mol:ceramide	-0.021	0.14	-10000	0	-0.48	32	32
GSN	0.025	0.077	0.29	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 8	-0.019	0.13	-10000	0	-0.47	31	31
FAS	0.011	0.006	-10000	0	-10000	0	0
BID	-0.033	0.081	0.32	3	-10000	0	3
MAP3K1	0.004	0.097	-10000	0	-0.28	15	15
MAP3K7	0.01	0.006	-10000	0	-10000	0	0
RB1	0.023	0.078	0.29	34	-0.32	1	35
CFLAR	0.014	0.004	-10000	0	-10000	0	0
HGF/MET	-0.15	0.22	-10000	0	-0.62	75	75
ARHGDIB	0.022	0.081	0.29	35	-10000	0	35
FADD	0.011	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.025	0.077	-10000	0	-0.29	35	35
NFKB1	-0.053	0.093	-10000	0	-0.32	16	16
MAPK8	-0.058	0.22	-10000	0	-0.45	102	102
DFFA	0.025	0.077	0.29	35	-10000	0	35
DNA fragmentation during apoptosis	0.025	0.077	0.29	35	-10000	0	35
FAS/FADD/MET	-0.059	0.077	-10000	0	-10000	0	0
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.089	-10000	0	-0.39	20	20
FAF1	0.011	0.007	-10000	0	-10000	0	0
PARP1	0.025	0.077	0.29	35	-10000	0	35
DFFB	0.025	0.077	0.29	35	-10000	0	35
CHUK	-0.045	0.083	-10000	0	-0.73	1	1
FASLG	-0.057	0.22	-10000	0	-0.65	49	49
FAS/FADD	0	0.001	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	73	73
LMNA	0.023	0.07	0.26	35	-10000	0	35
CASP6	0.025	0.077	0.29	35	-10000	0	35
CASP10	0.011	0.006	-10000	0	-10000	0	0
CASP3	0.03	0.094	0.35	38	-10000	0	38
PTPN13	0.005	0.085	-10000	0	-0.82	5	5
CASP8	0.008	0.045	0.46	3	-10000	0	3
IL6	-0.26	0.57	-10000	0	-1.4	98	98
MET	-0.11	0.16	-10000	0	-0.31	179	179
ICAD/CAD	0.023	0.072	0.27	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 10	-0.022	0.14	-10000	0	-0.49	32	32
activation of caspase activity by cytochrome c	-0.033	0.08	0.32	3	-10000	0	3
PAK2	0.025	0.077	0.29	35	-10000	0	35
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

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

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
MET/RANBP9	-0.075	0.097	-10000	0	-10000	0	0
CRKL	-0.032	0.11	-10000	0	-0.33	26	26
mol:PIP3	-0.019	0.033	0.69	1	-10000	0	1
AKT1	0.001	0.04	0.45	1	-0.53	2	3
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	-0.022	0.11	-10000	0	-10000	0	0
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
HGF/MET/SHIP2	-0.14	0.21	-10000	0	-0.6	73	73
MAP3K5	-0.019	0.11	-10000	0	-0.48	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.19	-10000	0	-0.55	73	73
AP1	-0.28	0.42	-10000	0	-0.87	151	151
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.27	0.4	-10000	0	-0.85	151	151
STAT3 (dimer)	-0.04	0.13	-10000	0	-0.34	73	73
GAB1/CRKL/SHP2/PI3K	-0.043	0.095	-10000	0	-0.59	3	3
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
CBL/CRK	-0.023	0.11	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1
ELK1	-0.049	0.062	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.04	0.073	-10000	0	-10000	0	0
PAK1	0.009	0.038	0.42	1	-0.5	2	3
HGF/MET/RANBP10	-0.14	0.21	-10000	0	-0.6	73	73
HRAS	-0.06	0.16	-10000	0	-0.43	73	73
DOCK1	-0.026	0.12	-10000	0	-0.55	4	4
GAB1	-0.042	0.12	-10000	0	-0.3	73	73
CRK	-0.032	0.11	-10000	0	-0.33	26	26
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.11	0.21	-10000	0	-0.6	73	73
JUN	-0.18	0.35	-10000	0	-0.82	109	109
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.071	0.1	-10000	0	-0.29	73	73
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.012	0.14	-10000	0	-0.65	2	2
GRB2/SHC	-0.039	0.097	-10000	0	-10000	0	0
FOS	-0.21	0.37	-10000	0	-0.82	128	128
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.049	0.062	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.14	0.21	-10000	0	-0.61	73	73
cell migration	-0.055	0.085	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.075	0.097	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.052	0.14	-10000	0	-0.36	73	73
MET/MUC20	-0.079	0.1	-10000	0	-0.21	179	179
RAP1B	-0.013	0.1	-10000	0	-10000	0	0
RAP1A	-0.013	0.1	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.14	0.21	-10000	0	-0.6	73	73
RAF1	-0.048	0.15	-10000	0	-0.45	27	27
STAT3	-0.041	0.13	-10000	0	-0.34	73	73
cell proliferation	-0.048	0.18	-10000	0	-0.45	73	73
RPS6KB1	-0.015	0.04	-10000	0	-10000	0	0
MAPK3	-0.05	0.057	-10000	0	-10000	0	0
MAPK1	-0.05	0.057	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.007	0.13	-10000	0	-0.59	13	13
SRC	-0.041	0.13	-10000	0	-0.33	73	73
PI3K	-0.042	0.1	-10000	0	-0.32	29	29
MET/Glomulin	-0.059	0.093	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.037	0.14	-10000	0	-0.42	27	27
MET	-0.11	0.16	-10000	0	-0.31	179	179
MAP4K1	-0.028	0.12	-10000	0	-0.34	30	30
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.037	0.14	-10000	0	-0.42	27	27
BAD	0.009	0.038	0.42	1	-0.5	2	3
MAP2K4	-0.009	0.1	-10000	0	-0.43	5	5
SHP2/GRB2/SOS1/GAB1	-0.058	0.091	-10000	0	-0.38	1	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	-0.049	0.1	-10000	0	-0.32	26	26
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	73	73
RASA1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.041	0.11	-10000	0	-0.33	26	26
PDPK1	-0.009	0.044	0.52	1	-0.58	2	3
HGF/MET/SHIP	-0.15	0.21	-10000	0	-0.6	73	73

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	-0.035	0.12	-10000	0	-0.51	26	26
ER alpha/Gai/GDP/Gbeta gamma	0.006	0.15	-10000	0	-0.48	35	35
AKT1	-0.015	0.2	-10000	0	-0.86	25	25
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.014	0.2	-10000	0	-0.87	25	25
mol:Ca2+	-0.099	0.23	-10000	0	-0.5	114	114
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.071	0.18	-10000	0	-0.58	51	51
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.012	0.19	0.82	25	-10000	0	25
RhoA/GTP	-0.026	0.089	-10000	0	-0.41	23	23
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.037	0.13	-10000	0	-0.59	23	23
regulation of stress fiber formation	-0.013	0.11	0.36	21	-10000	0	21
E2/ERA-ERB (dimer)	-0.042	0.14	-10000	0	-0.57	26	26
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.034	0.11	-10000	0	-0.51	23	23
pseudopodium formation	0.013	0.11	-10000	0	-0.36	21	21
E2/ER alpha (dimer)/PELP1	-0.037	0.12	-10000	0	-0.56	23	23
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.82	1	1
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
HRAS	0.012	0.021	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.012	0.15	-10000	0	-0.6	24	24
E2/ER beta (dimer)	-0.005	0.058	-10000	0	-0.64	4	4
mol:GDP	-0.036	0.13	-10000	0	-0.56	26	26
mol:NADP	0.012	0.15	-10000	0	-0.6	24	24
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.1	0.24	-10000	0	-0.52	114	114
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.11	0.24	-10000	0	-0.54	114	114
PLCB2	-0.12	0.25	-10000	0	-0.54	113	113
IGF1	-0.18	0.35	-10000	0	-0.8	118	118
mol:L-citrulline	0.012	0.15	-10000	0	-0.6	24	24
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.027	0.14	-10000	0	-0.78	16	16
JNK cascade	-0.005	0.058	-10000	0	-0.64	4	4
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.006	0.076	-10000	0	-0.82	4	4
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.048	0.19	-10000	0	-0.53	54	54
Gq family/GDP/Gbeta gamma	-0.056	0.17	-10000	0	-0.53	22	22
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.081	-10000	0	-0.36	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.037	0.13	-10000	0	-0.59	23	23
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.044	0.14	-10000	0	-0.64	23	23
STRN	-0.039	0.2	-10000	0	-0.82	30	30
GNAL	-0.093	0.28	-10000	0	-0.82	61	61
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.015	0.052	-10000	0	-0.55	4	4
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
HBEGF	-0.004	0.16	-10000	0	-0.52	28	28
cAMP biosynthetic process	-0.09	0.19	-10000	0	-0.48	83	83
SRC	0.014	0.14	-10000	0	-0.5	24	24
PI3K	-0.004	0.05	-10000	0	-0.63	3	3
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.031	0.12	-10000	0	-0.5	26	26
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-10000	0	-0.53	38	38
Gs family/GTP	-0.092	0.19	-10000	0	-0.49	83	83
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	0.013	0.14	-10000	0	-0.56	24	24
mol:DAG	-0.1	0.24	-10000	0	-0.52	114	114
Gs family/GDP/Gbeta gamma	-0.074	0.16	-10000	0	-0.41	83	83
MSN	0.012	0.12	-10000	0	-0.39	21	21
Gq family/GTP	-0.15	0.24	-10000	0	-0.57	113	113
mol:PI-3-4-5-P3	-0.012	0.2	-10000	0	-0.83	25	25
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.013	0.14	0.56	24	-10000	0	24
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.033	0.12	-10000	0	-0.52	26	26
NOS3	0.01	0.16	-10000	0	-0.64	24	24
GNA11	-0.002	0.11	-10000	0	-0.82	9	9
MAPKKK cascade	-0.008	0.19	-10000	0	-0.54	51	51
E2/ER alpha (dimer)/PELP1/Src	-0.039	0.14	-10000	0	-0.63	23	23
ruffle organization	0.013	0.11	-10000	0	-0.36	21	21
ROCK2	0.003	0.13	-10000	0	-0.41	43	43
GNA14	-0.18	0.35	-10000	0	-0.82	112	112
GNA15	-0.013	0.094	-10000	0	-0.33	37	37
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.027	0.19	-10000	0	-0.52	46	46
MMP2	0.015	0.15	-10000	0	-0.68	11	11

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.017	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.011	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.018	0.071	-9999	-0.56	5	5
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.026	-9999	-0.31	3	3
GRK1	-0.067	0.25	-9999	-0.81	47	47
CNG Channel	-0.028	0.085	-9999	-0.52	9	9
mol:Na +	-0.023	0.082	-9999	-0.46	13	13
mol:ADP	-0.067	0.25	-9999	-0.81	47	47
RGS9-1/Gbeta5/R9AP	-0.092	0.21	-9999	-0.56	79	79
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.024	0.084	-9999	-0.47	13	13
CNGB1	0	0.062	-9999	-0.31	18	18
RDH5	-0.2	0.16	-9999	-0.31	314	314
SAG	0.002	0.015	-9999	-0.31	1	1
mol:Ca2+	0.016	0.088	-9999	-0.44	13	13
Na + (4 Units)	-0.021	0.075	-9999	-0.42	13	13
RGS9	-0.078	0.26	-9999	-0.8	54	54
GNB1/GNGT1	-0.003	0.024	-9999	-10000	0	0
GNAT1/GDP	-0.081	0.18	-9999	-0.49	79	79
GUCY2D	-0.011	0.11	-9999	-0.43	26	26
GNGT1	-0.004	0.038	-9999	-0.31	7	7
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.074	-9999	-0.48	5	5
mol:11-cis-retinal	-0.2	0.16	-9999	-0.31	314	314
mol:cGMP	-0.016	0.071	-9999	-0.48	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.14	0.098	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0.001	0.091	-9999	-0.57	10	10
Metarhodopsin II	-0.05	0.15	-9999	-0.52	46	46
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.076	-9999	-0.51	9	9
RGS9BP	-0.037	0.2	-9999	-0.82	29	29
Metarhodopsin II/Transducin	0.011	0.015	-9999	-10000	0	0
GCAP Family/Ca ++	-0.005	0.043	-9999	-0.52	3	3
PDE6A/B	-0.012	0.047	-9999	-10000	0	0
mol:Pi	-0.092	0.21	-9999	-0.56	79	79
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.023	-9999	-10000	0	0
PDE6B	0.013	0	-9999	-10000	0	0
PDE6A	-0.008	0.076	-9999	-0.31	28	28
PDE6G	-0.017	0.12	-9999	-0.38	37	37
RHO	0.006	0.016	-9999	-0.31	1	1
PDE6	-0.093	0.18	-9999	-0.48	82	82
GUCA1A	0.004	0.03	-9999	-0.31	4	4
GC2/GCAP Family	-0.005	0.043	-9999	-0.52	3	3
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.007	0.067	-9999	-0.7	4	4

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.013	0.014	-9999	-10000	0	0
REL	-0.033	0.2	-9999	-0.82	30	30
HDAC7	-0.031	0.14	-9999	-0.63	15	15
JUN	-0.18	0.35	-9999	-0.82	109	109
EP300	0.013	0.001	-9999	-10000	0	0
KAT2B	0.013	0.001	-9999	-10000	0	0
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.002	0.095	-9999	-0.65	10	10
FOXO1	0.012	0.001	-9999	-10000	0	0
T-DHT/AR	-0.044	0.15	-9999	-0.65	17	17
MAP2K6	-0.01	0.12	-9999	-0.78	11	11
BRM/BAF57	-0.002	0.003	-9999	-10000	0	0
MAP2K4	0.009	0.007	-9999	-10000	0	0
SMARCA2	0.009	0.007	-9999	-10000	0	0
PDE9A	0.011	0.056	-9999	-10000	0	0
NCOA2	-0.07	0.24	-9999	-0.83	44	44
CEBPA	0.006	0.085	-9999	-0.82	5	5
EHMT2	0.009	0.006	-9999	-10000	0	0
cell proliferation	-0.067	0.15	-9999	-0.54	15	15
NR0B1	-0.002	0.041	-9999	-0.31	8	8
EGR1	-0.17	0.34	-9999	-0.83	102	102
RXRs/9cRA	-0.13	0.059	-9999	-0.5	4	4
AR/RACK1/Src	-0.11	0.16	-9999	-0.66	17	17
AR/GR	-0.13	0.2	-9999	-0.36	141	141
GNB2L1	0.007	0.007	-9999	-10000	0	0
PKN1	0.013	0.001	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.006	0.005	-9999	-10000	0	0
MAPK8	0	0.09	-9999	-0.64	9	9
T-DHT/AR/TIF2/CARM1	-0.12	0.23	-9999	-0.69	52	52
SRC	-0.003	0.11	-9999	-0.54	17	17
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.4	0.57	-9999	-1.3	137	137
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.054	0.14	-9999	-0.66	17	17
TMPRSS2	-0.061	0.32	-9999	-1.2	32	32
RXRG	-0.28	0.12	-9999	-0.32	427	427
mol:9cRA	-0.002	0.002	-9999	-10000	0	0
RXRA	0.012	0.001	-9999	-10000	0	0
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.007	0.007	-9999	-10000	0	0
NR2C2	-0.003	0.11	-9999	-0.82	9	9
KLK2	-0.48	0.43	-9999	-0.83	279	279
AR	-0.15	0.22	-9999	-0.38	206	206
SENP1	0.012	0.002	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.023	0.015	-9999	-10000	0	0
SRY	0.01	0.015	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
MYST2	0.014	0.002	-9999	-10000	0	0
HOXB13	-0.015	0.054	-9999	-0.32	13	13
T-DHT/AR/RACK1/Src	-0.076	0.15	-9999	-0.66	17	17
positive regulation of transcription	0.013	0.015	-9999	-0.31	1	1
DNAJA1	0.013	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.005	-9999	-10000	0	0
NCOA1	0.013	0.009	-9999	-10000	0	0
SPDEF	-0.026	0.1	-9999	-0.32	52	52
T-DHT/AR/TIF2	-0.053	0.16	-9999	-0.45	46	46
T-DHT/AR/Hsp90	-0.055	0.14	-9999	-0.67	17	17
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.005	0.12	-9999	-0.57	17	17
SIRT1	0.011	0.038	-9999	-0.82	1	1
ZMIZ2	0.023	0.015	-9999	-10000	0	0
POU2F1	0.031	0.02	-9999	-0.3	1	1
T-DHT/AR/DAX-1	-0.074	0.14	-9999	-0.67	17	17
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.009	0.007	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.038	0.038	-9999	-10000	0	0
VDR	0.013	0.015	-9999	-0.31	1	1
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.059	0.11	-9999	-0.35	49	49
RXRs/LXRs/DNA/Oxysterols	-0.049	0.16	-9999	-0.46	58	58
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.022	0.083	-9999	-0.34	23	23
RXRs/NUR77	-0.26	0.25	-9999	-0.63	144	144
RXRs/PPAR	-0.055	0.065	-9999	-0.4	11	11
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-9999	-0.21	1	1
RARs/VDR/DNA/Vit D3	-0.013	0.078	-9999	-0.48	13	13
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-9999	-0.31	1	1
RARs/RARs/DNA/9cRA	-0.012	0.078	-9999	-0.48	13	13
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.054	0.031	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.022	0.083	-9999	-0.34	23	23
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0.01	-9999	-0.21	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.083	-9999	-0.53	5	5
NR1H4	0.001	0.033	-9999	-0.31	5	5
RXRs/LXRs/DNA	-0.099	0.093	-9999	-0.58	4	4
NR1H2	0.016	0.012	-9999	-10000	0	0
NR1H3	0.015	0.014	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.068	-9999	-0.52	4	4
NR4A1	-0.23	0.38	-9999	-0.82	142	142
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.048	0.049	-9999	-0.33	4	4
RXRG	-0.28	0.12	-9999	-0.32	427	427
RXR alpha/CCPG	0.021	0.01	-9999	-10000	0	0
RXRA	0.015	0.012	-9999	-10000	0	0
RXRB	0.015	0.014	-9999	-10000	0	0
THRB	-0.006	0.12	-9999	-0.82	11	11
PPARG	-0.002	0.1	-9999	-0.61	12	12
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.42	-9999	-1.3	58	58
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.048	0.16	-9999	-0.46	58	58
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.009	0.14	-9999	-0.82	13	13
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.45	166	166
SREBF1	-0.038	0.14	-9999	-0.62	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.083	-9999	-0.53	5	5
ABCA1	-0.038	0.14	-9999	-0.43	47	47
RARs/THRs	-0.023	0.1	-9999	-0.48	23	23
RXRs/FXR	-0.12	0.072	-9999	-0.56	4	4
BCL2	-0.047	0.22	-9999	-0.82	35	35

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.005	0.12	-9999	-0.78	11	11
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.15	0.15	-9999	-0.28	278	278
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.011	0.03	-9999	-0.31	4	4
p38 alpha/TAB1	-0.047	0.068	-9999	-0.3	6	6
PRKG1	-0.21	0.37	-9999	-0.82	131	131
DUSP8	0.002	0.084	-9999	-0.52	10	10
PGK/cGMP/p38 alpha	-0.16	0.2	-9999	-0.47	134	134
apoptosis	-0.046	0.066	-9999	-0.29	6	6
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.12	0.31	-9999	-0.82	78	78
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0.015	-9999	-0.31	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.06	0.13	-9999	-0.38	14	14
BLK	-0.25	0.38	-9999	-0.76	163	163
HCK	-0.008	0.08	-9999	-0.31	31	31
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.01	0.043	-9999	-0.48	3	3
TRAF6/MEKK3	-0.002	0.033	-9999	-0.51	2	2
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.027	0.092	-9999	-0.34	5	5
positive regulation of innate immune response	-0.059	0.14	-9999	-0.41	12	12
LCK	-0.01	0.11	-9999	-0.44	25	25
p38alpha-beta/MKP7	-0.049	0.13	-9999	-0.45	6	6
p38alpha-beta/MKP5	-0.051	0.13	-9999	-0.48	7	7
PGK/cGMP	-0.17	0.28	-9999	-0.64	131	131
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.12	0.2	-9999	-0.49	73	73
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.47	0.41	-9999	-0.82	278	278

×

ErbB2/ErbB3 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
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.042	0.1	-9999	-0.38	21	21
NFATC4	-0.001	0.11	-9999	-0.5	3	3
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.046	0.13	-9999	-0.41	54	54
JUN	0.002	0.097	-9999	-0.28	11	11
HRAS	0.011	0.021	-9999	-0.32	2	2
DOCK7	-0.016	0.14	-9999	-0.38	57	57
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.056	0.16	-9999	-0.49	54	54
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.023	0.064	-9999	-0.37	2	2
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.026	0.15	-9999	-0.44	54	54
RAF1	-0.004	0.13	-9999	-0.4	21	21
ErbB2/ErbB3/neuregulin 2	-0.07	0.18	-9999	-0.52	64	64
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.022	0.083	-9999	-0.31	5	5
mol:PI-3-4-5-P3	0	0.002	-9999	-10000	0	0
cell proliferation	-0.13	0.33	-9999	-0.68	114	114
FOS	-0.11	0.28	-9999	-0.52	151	151
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.046	0.13	-9999	-0.41	54	54
MAPK3	-0.085	0.26	-9999	-0.5	110	110
MAPK1	-0.085	0.26	-9999	-0.5	110	110
JAK2	-0.014	0.14	-9999	-0.38	55	55
NF2	-0.002	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.016	0.13	-9999	-0.38	54	54
NRG1	-0.068	0.24	-9999	-0.8	47	47
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.014	0.13	-9999	-0.35	62	62
MAPK9	-0.023	0.061	-9999	-0.29	1	1
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.008	0.12	-9999	-0.74	12	12
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.003	0.01	-9999	-10000	0	0
STAT3 (dimer)	0	0.003	-9999	-10000	0	0
RNF41	0.027	0.007	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.032	0.088	-9999	-0.38	2	2
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.057	0.2	-9999	-0.43	41	41
myelination	0.009	0.11	-9999	-0.46	3	3
PPP3CB	-0.011	0.13	-9999	-0.36	54	54
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-9999	-0.65	2	2
NRG2	-0.083	0.26	-9999	-0.8	57	57
mol:GDP	-0.016	0.13	-9999	-0.37	54	54
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.006	0.14	-9999	-0.41	21	21
SRC	0.013	0.015	-9999	-0.31	1	1
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.014	0.14	-9999	-0.38	55	55
MAP2K1	-0.077	0.23	-9999	-0.58	33	33
heart morphogenesis	-0.046	0.13	-9999	-0.41	54	54
RAS family/GDP	-0.036	0.1	-9999	-0.64	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.009	-9999	-10000	0	0
CHRNE	0.01	0.034	-9999	-0.13	17	17
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.046	0.13	-9999	-0.41	54	54
CDC42	0.013	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.042	-10000	0	-0.31	8	8
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.064	0.15	0.54	9	-10000	0	9
IL27/IL27R/JAK1	-0.12	0.19	-10000	0	-0.66	8	8
TBX21	-0.089	0.22	-10000	0	-0.66	30	30
IL12B	-0.005	0.092	-10000	0	-0.55	11	11
IL12A	-0.059	0.2	-10000	0	-0.62	53	53
IL6ST	-0.11	0.29	-10000	0	-0.83	68	68
IL27RA/JAK1	0.013	0.026	-10000	0	-10000	0	0
IL27	0.002	0.037	-10000	0	-0.32	6	6
TYK2	0.012	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.063	0.16	-10000	0	-0.51	1	1
T-helper 2 cell differentiation	0.064	0.15	0.54	9	-10000	0	9
T cell proliferation during immune response	0.064	0.15	0.54	9	-10000	0	9
MAPKKK cascade	-0.064	0.15	-10000	0	-0.54	9	9
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.049	-10000	0	-0.32	11	11
IL12RB1	-0.022	0.12	-10000	0	-0.36	44	44
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.089	0.21	-10000	0	-0.64	28	28
IL27/IL27R/JAK2/TYK2	-0.065	0.15	-10000	0	-0.55	9	9
positive regulation of T cell mediated cytotoxicity	-0.064	0.15	-10000	0	-0.54	9	9
STAT1 (dimer)	-0.12	0.24	0.52	16	-0.77	15	31
JAK2	0.012	0.039	-10000	0	-0.84	1	1
JAK1	0.014	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.054	0.14	-10000	0	-0.52	9	9
T cell proliferation	-0.16	0.24	-10000	0	-0.54	100	100
IL12/IL12R/TYK2/JAK2	-0.055	0.17	-10000	0	-0.68	14	14
IL17A	-0.064	0.16	-10000	0	-0.51	1	1
mast cell activation	0.064	0.15	0.54	9	-10000	0	9
IFNG	-0.02	0.049	-10000	0	-0.13	65	65
T cell differentiation	-0.005	0.008	-10000	0	-0.022	58	58
STAT3 (dimer)	-0.054	0.14	-10000	0	-0.52	9	9
STAT5A (dimer)	-0.054	0.14	-10000	0	-0.52	9	9
STAT4 (dimer)	-0.074	0.16	-10000	0	-0.52	23	23
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
T cell activation	-0.012	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.062	0.18	-10000	0	-0.69	5	5
GATA3	-0.045	0.34	-10000	0	-1.5	25	25
IL18	-0.025	0.12	-10000	0	-0.3	58	58
positive regulation of mast cell cytokine production	-0.053	0.14	-10000	0	-0.51	9	9
IL27/EBI3	-0.098	0.12	-10000	0	-0.44	6	6
IL27RA	0.004	0.027	-10000	0	-10000	0	0
IL6	-0.17	0.34	-10000	0	-0.71	123	123
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.002	0.013	-10000	0	-10000	0	0
IL1B	-0.042	0.18	-10000	0	-0.64	38	38
EBI3	-0.15	0.17	-10000	0	-0.32	231	231
TNF	-0.07	0.21	-10000	0	-0.64	58	58

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.047	0.16	-9999	-0.54	40	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.051	-9999	-0.6	1	1
AP1	-0.26	0.36	-9999	-0.69	176	176
mol:PIP3	-0.042	0.13	-9999	-0.52	16	16
AKT1	-0.029	0.097	-9999	-0.58	5	5
PTK2B	0	0.087	-9999	-0.27	40	40
RHOA	0.031	0.047	-9999	-0.26	1	1
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.004	0.073	-9999	-10000	0	0
MAGI3	0.012	0.038	-9999	-0.82	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.016	0.14	-9999	-0.45	40	40
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.008	0.089	-9999	-0.36	9	9
NF kappa B1 p50/RelA	-0.047	0.12	-9999	-0.55	13	13
endothelial cell migration	-0.03	0.21	-9999	-0.64	42	42
ADCY4	-0.017	0.19	-9999	-0.62	41	41
ADCY5	-0.048	0.21	-9999	-0.65	44	44
ADCY6	-0.017	0.19	-9999	-0.62	41	41
ADCY7	-0.017	0.19	-9999	-0.62	41	41
ADCY1	-0.019	0.2	-9999	-0.62	41	41
ADCY2	-0.041	0.22	-9999	-0.66	42	42
ADCY3	-0.017	0.19	-9999	-0.62	41	41
ADCY8	-0.058	0.2	-9999	-0.63	44	44
ADCY9	-0.017	0.19	-9999	-0.62	41	41
GSK3B	0.008	0.083	-9999	-0.3	13	13
arachidonic acid secretion	-0.01	0.19	-9999	-0.57	41	41
GNG2	0.012	0.038	-9999	-0.82	1	1
TRIP6	0.026	0.008	-9999	-10000	0	0
GNAO1	-0.042	0.21	-9999	-0.6	55	55
HRAS	0.012	0.021	-9999	-0.31	2	2
NFKBIA	0.01	0.079	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.033	0.099	-9999	-0.97	5	5
JUN	-0.18	0.35	-9999	-0.82	109	109
LPA/LPA2/NHERF2	-0.001	0.007	-9999	-10000	0	0
TIAM1	-0.043	0.12	-9999	-1.2	5	5
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.004	0.074	-9999	-10000	0	0
PLCB3	0.03	0.008	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	128	128
positive regulation of mitosis	-0.01	0.19	-9999	-0.57	41	41
LPA/LPA1-2-3	-0.052	0.16	-9999	-0.54	40	40
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	0.003	0.11	-9999	-0.36	40	40
GNAZ	-0.022	0.17	-9999	-0.57	42	42
EGFR/PI3K-beta/Gab1	-0.044	0.13	-9999	-0.54	16	16
positive regulation of dendritic cell cytokine production	-0.052	0.15	-9999	-0.54	40	40
LPA/LPA2/MAGI-3	-0.002	0.028	-9999	-0.6	1	1
ARHGEF1	-0.002	0.15	-9999	-0.5	40	40
GNAI2	-0.022	0.17	-9999	-0.57	42	42
GNAI3	-0.022	0.17	-9999	-0.57	42	42
GNAI1	-0.024	0.18	-9999	-0.57	43	43
LPA/LPA3	-0.01	0.043	-9999	-0.27	1	1
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.058	0.19	-9999	-0.66	42	42
HB-EGF/EGFR	-0.053	0.17	-9999	-0.54	46	46
HBEGF	-0.06	0.19	-9999	-0.62	42	42
mol:DAG	0.004	0.074	-9999	-10000	0	0
cAMP biosynthetic process	-0.029	0.2	-9999	-0.56	54	54
NFKB1	0.012	0.038	-9999	-0.82	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.01	0.079	-9999	-10000	0	0
GNAQ	0.019	0.028	-9999	-10000	0	0
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.003	0.065	-9999	-0.31	20	20
LPAR1	-0.054	0.24	-9999	-0.84	40	40
IL8	-0.13	0.2	-9999	-0.47	64	64
PTK2	-0.011	0.16	-9999	-0.5	40	40
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.016	0.14	-9999	-0.45	40	40
EGFR	0.006	0.076	-9999	-0.82	4	4
PLCG1	-0.015	0.085	-9999	-0.31	9	9
PLD2	-0.011	0.16	-9999	-0.5	40	40
G12/G13	-0.046	0.15	-9999	-0.53	40	40
PI3K-beta	-0.033	0.12	-9999	-0.71	5	5
cell migration	-0.016	0.059	-9999	-0.27	5	5
SLC9A3R2	0.013	0	-9999	-10000	0	0
PXN	0.002	0.12	-9999	-0.36	40	40
HRAS/GTP	-0.011	0.19	-9999	-0.59	41	41
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.57	79	79
PRKCE	0.007	0.076	-9999	-0.82	4	4
PRKCD	0.012	0.071	-9999	-10000	0	0
Gi(beta/gamma)	-0.01	0.19	-9999	-0.59	41	41
mol:LPA	0.003	0.018	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.031	0.13	-9999	-0.45	40	40
MAPKKK cascade	-0.01	0.19	-9999	-0.57	41	41
contractile ring contraction involved in cytokinesis	0.031	0.046	-9999	-0.26	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.086	0.2	-9999	-0.44	112	112
GNA15	0.009	0.055	-9999	-0.43	1	1
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.008	0.091	-9999	-0.37	9	9
GNA11	0.011	0.067	-9999	-0.43	9	9
Rac1/GTP	-0.035	0.11	-9999	-1	5	5
MMP2	-0.03	0.21	-9999	-0.65	42	42

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.055	0.16	-9999	-0.55	40	40
MAP4K1	-0.019	0.13	-9999	-0.41	37	37
MAP3K8	-0.001	0.11	-9999	-0.82	8	8
PRKCB	-0.027	0.13	-9999	-0.36	52	52
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.014	0.11	-9999	-0.56	5	5
JUN	-0.1	0.24	-9999	-0.51	119	119
MAP3K7	0.014	0.11	-9999	-0.56	5	5
GRAP2	-0.042	0.21	-9999	-0.78	34	34
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.02	0.11	-9999	-0.52	7	7
LAT	0.006	0.077	-9999	-0.72	5	5
LCP2	0.009	0.039	-9999	-0.31	7	7
MAPK8	-0.001	0.14	-9999	-0.76	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.005	0.11	-9999	-0.37	32	32
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.051	0.15	-9999	-0.52	40	40

×

BCR signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.18	-9999	-0.45	62	62
IKBKB	-0.018	0.071	-9999	-0.33	4	4
AKT1	-0.041	0.1	-9999	-0.27	21	21
IKBKG	-0.017	0.074	-9999	-0.33	5	5
CALM1	-0.035	0.085	-9999	-0.35	2	2
PIK3CA	0.008	0.066	-9999	-0.82	3	3
MAP3K1	-0.073	0.18	-9999	-0.65	16	16
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.045	0.089	-9999	-0.38	2	2
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.082	0.13	-9999	-0.28	110	110
LYN	0.013	0	-9999	-10000	0	0
BLNK	0.013	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
BCR complex	-0.17	0.24	-9999	-0.52	135	135
CD22	-0.15	0.22	-9999	-0.51	104	104
CAMK2G	-0.025	0.081	-9999	-0.32	2	2
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	24	24
SHC/GRB2/SOS1	-0.096	0.15	-9999	-10000	0	0
GO:0007205	-0.045	0.09	-9999	-0.38	2	2
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.035	0.086	-9999	-0.36	2	2
NFATC1	-0.069	0.16	-9999	-0.54	20	20
B-cell antigen/BCR complex	-0.17	0.24	-9999	-0.52	135	135
PAG1/CSK	-0.001	0.029	-9999	-0.63	1	1
NFKBIB	0.002	0.028	-9999	-0.11	3	3
HRAS	-0.037	0.099	-9999	-0.35	2	2
NFKBIA	0.003	0.027	-9999	-0.11	3	3
NF-kappa-B/RelA/I kappa B beta	0.008	0.024	-9999	-0.2	1	1
RasGAP/Csk	-0.14	0.2	-9999	-0.49	94	94
mol:GDP	-0.041	0.083	-9999	-0.36	2	2
PTEN	0.012	0.038	-9999	-0.82	1	1
CD79B	-0.029	0.11	-9999	-0.31	62	62
NF-kappa-B/RelA/I kappa B alpha	0.009	0.024	-9999	-0.2	1	1
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.086	0.18	-9999	-0.43	74	74
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.051	0.087	-9999	-0.38	2	2
CSK	0.013	0	-9999	-10000	0	0
FOS	-0.14	0.21	-9999	-0.47	129	129
CHUK	-0.017	0.074	-9999	-0.35	4	4
IBTK	0.013	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.066	0.094	-9999	-0.49	8	8
PTPN6	-0.14	0.21	-9999	-0.6	51	51
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.035	-9999	-0.13	18	18
VAV2	-0.13	0.19	-9999	-0.51	41	41
ubiquitin-dependent protein catabolic process	0.007	0.027	-9999	-0.11	3	3
BTK	-0.019	0.16	-9999	-1.2	8	8
CD19	-0.15	0.2	-9999	-0.45	98	98
MAP4K1	-0.019	0.13	-9999	-0.41	37	37
CD72	0.012	0.021	-9999	-0.31	2	2
PAG1	0.012	0.038	-9999	-0.82	1	1
MAPK14	-0.055	0.16	-9999	-0.52	16	16
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.034	0.088	-9999	-0.32	2	2
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.061	0.17	-9999	-0.43	71	71
RAF1	-0.027	0.094	-9999	-0.34	1	1
RasGAP/p62DOK/SHIP	-0.14	0.19	-9999	-0.47	93	93
CD79A	-0.19	0.3	-9999	-0.82	74	74
re-entry into mitotic cell cycle	-0.081	0.13	-9999	-0.28	108	108
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.008	0.083	-9999	-10000	0	0
MAPK1	-0.008	0.083	-9999	-10000	0	0
CD72/SHP1	-0.1	0.21	-9999	-0.56	51	51
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.062	0.17	-9999	-0.53	24	24
actin cytoskeleton organization	-0.086	0.18	-9999	-0.68	11	11
NF-kappa-B/RelA	0.022	0.045	-9999	-0.2	1	1
Calcineurin	-0.035	0.059	-9999	-10000	0	0
PI3K	-0.13	0.16	-9999	-0.54	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.055	0.085	-9999	-0.34	2	2
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.11	0.24	-9999	-0.9	25	25
DAPP1	-0.13	0.26	-9999	-1.2	18	18
cytokine secretion	-0.064	0.15	-9999	-0.5	20	20
mol:DAG	-0.051	0.087	-9999	-0.38	2	2
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.018	0.089	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.17	0.23	-9999	-0.58	94	94
mol:PI-3-4-5-P3	-0.096	0.12	-9999	-0.38	26	26
ETS1	-0.016	0.076	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.17	-9999	-0.46	74	74
B-cell antigen/BCR complex/LYN	-0.12	0.2	-9999	-0.49	81	81
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
RAC1	-0.092	0.19	-9999	-0.75	11	11
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.55	81	81
CARD11	-0.074	0.12	-9999	-0.51	12	12
FCGR2B	-0.029	0.18	-9999	-0.75	27	27
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
IKK complex	0	0.035	-9999	-0.14	2	2
PTPRC	-0.033	0.18	-9999	-0.59	37	37
PDPK1	-0.043	0.1	-9999	-0.27	21	21
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.013	0	-9999	-10000	0	0
POU2F2	0.009	0.024	-9999	-0.089	1	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.12	0.1	-9999	-0.65	7	7
EPHB2	0.008	0.066	-9999	-0.82	3	3
Syndecan-2/TACI	-0.13	0.25	-9999	-0.56	117	117
LAMA1	-0.05	0.22	-9999	-0.81	37	37
Syndecan-2/alpha2 ITGB1	-0.073	0.11	-9999	-0.47	24	24
HRAS	0.012	0.021	-9999	-0.31	2	2
Syndecan-2/CASK	-0.008	0.066	-9999	-0.55	7	7
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.025	0.097	-9999	-0.5	16	16
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.007	0.06	-9999	-0.5	7	7
LAMA3	-0.026	0.16	-9999	-0.59	31	31
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.066	-9999	-0.82	3	3
Syndecan-2/MMP2	0.008	0.1	-9999	-0.58	13	13
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.079	0.099	-9999	-10000	0	0
dendrite morphogenesis	0.014	0.081	-9999	-0.54	10	10
Syndecan-2/GM-CSF	-0.11	0.099	-9999	-0.57	7	7
determination of left/right symmetry	0.012	0.078	-9999	-0.63	7	7
Syndecan-2/PKC delta	0.018	0.068	-9999	-0.54	7	7
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.087	0.092	-9999	-0.52	7	7
MAPK1	-0.087	0.092	-9999	-0.52	7	7
Syndecan-2/RACK1	-0.007	0.057	-9999	-0.47	7	7
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.078	-9999	-0.63	7	7
ITGA2	-0.12	0.16	-9999	-0.31	190	190
MAPK8	0.017	0.1	-9999	-0.55	16	16
Syndecan-2/alpha2/beta1 Integrin	-0.087	0.14	-9999	-0.52	40	40
Syndecan-2/Kininogen	-0.007	0.079	-9999	-0.55	7	7
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.031	0.058	-9999	-0.44	7	7
Syndecan-2/CASK/Protein 4.1	-0.007	0.06	-9999	-0.5	7	7
extracellular matrix organization	0.014	0.071	-9999	-0.54	7	7
actin cytoskeleton reorganization	-0.12	0.1	-9999	-0.65	7	7
Syndecan-2/Caveolin-2/Ras	-0.011	0.077	-9999	-0.55	9	9
Syndecan-2/Laminin alpha3	-0.008	0.13	-9999	-0.55	24	24
Syndecan-2/RasGAP	-0.007	0.054	-9999	-0.44	7	7
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.014	0.081	-9999	-0.55	10	10
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.057	-9999	-0.42	7	7
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.19	0.35	-9999	-0.79	120	120
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.079	0.099	-9999	-10000	0	0
Syndecan-2/Synbindin	0.018	0.068	-9999	-0.54	7	7
TGFB1	0.008	0.042	-9999	-0.31	8	8
CASP3	0.027	0.063	-9999	-0.49	7	7
FN1	-0.22	0.15	-9999	-10000	0	0
Syndecan-2/IL8	-0.038	0.12	-9999	-0.55	17	17
SDC2	0.012	0.078	-9999	-0.63	7	7
KNG1	-0.014	0.077	-9999	-0.31	30	30
Syndecan-2/Neurofibromin	0.018	0.068	-9999	-0.54	7	7
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.21	0.15	-9999	-0.31	326	326
Syndecan-2/TGFB1	0.015	0.072	-9999	-0.54	7	7
Syndecan-2/Syntenin/PI-4-5-P2	-0.007	0.06	-9999	-0.5	7	7
Syndecan-2/Ezrin	-0.007	0.059	-9999	-0.49	7	7
PRKACA	0.027	0.063	-9999	-0.49	7	7
angiogenesis	-0.037	0.12	-9999	-0.54	17	17
MMP2	-0.001	0.1	-9999	-0.82	7	7
IL8	-0.081	0.18	-9999	-0.36	123	123
calcineurin-NFAT signaling pathway	-0.12	0.25	-9999	-0.56	117	117

×

Signaling events mediated by PTP1B

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
PDGFRB	0.012	0.038	-10000	0	-0.82	1	1
Jak2/Leptin Receptor	-0.023	0.094	-10000	0	-0.41	12	12
PTP1B/AKT1	-0.002	0.063	-10000	0	-0.32	3	3
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.011	0.07	-10000	0	-0.34	4	4
EGFR	0.005	0.077	-10000	0	-0.83	4	4
EGF/EGFR	-0.083	0.18	-10000	0	-0.5	72	72
CSF1	-0.001	0.11	-10000	0	-0.82	8	8
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.014	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.099	0.12	-10000	0	-0.45	20	20
Insulin Receptor/Insulin	-0.013	0.04	-10000	0	-10000	0	0
HCK	-0.008	0.08	-10000	0	-0.31	31	31
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.002	0.066	-10000	0	-0.34	3	3
EGF	-0.11	0.29	-10000	0	-0.79	74	74
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.017	0.099	-10000	0	-0.39	5	5
TXN	0.011	0.016	-10000	0	-0.32	1	1
PTP1B/IRS1/GRB2	-0.053	0.17	-10000	0	-0.5	56	56
cell migration	0.011	0.07	0.34	4	-10000	0	4
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.045	0.2	-10000	0	-0.6	46	46
ITGA2B	-0.074	0.26	-10000	0	-0.82	50	50
CSF1R	0.008	0.05	-10000	0	-0.4	6	6
Prolactin Receptor/Prolactin	-0.04	0.15	-10000	0	-0.64	26	26
FGR	0.011	0.03	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.003	0.066	-10000	0	-0.34	3	3
Crk/p130 Cas	0.001	0.06	-10000	0	-0.35	2	2
DOK1	0.007	0.062	-10000	0	-0.32	2	2
JAK2	-0.011	0.088	-10000	0	-0.38	12	12
Jak2/Leptin Receptor/Leptin	-0.056	0.14	-10000	0	-0.58	28	28
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.011	0.07	-10000	0	-0.32	5	5
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.19	0.2	-10000	0	-0.34	275	275
SRC	0.012	0.029	-10000	0	-10000	0	0
ITGB3	-0.012	0.14	-10000	0	-0.83	14	14
CAT1/PTP1B	-0.089	0.15	-10000	0	-0.39	52	52
CAPN1	0.013	0.003	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.015	0.053	-10000	0	-0.58	3	3
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.055	0.15	-10000	0	-0.63	27	27
negative regulation of transcription	-0.01	0.088	-10000	0	-0.38	12	12
FCGR2A	-0.007	0.084	-10000	0	-0.33	28	28
FER	0.007	0.067	-10000	0	-0.83	3	3
alphaIIb/beta3 Integrin	-0.082	0.23	-10000	0	-0.68	59	59
BLK	-0.25	0.38	-10000	0	-0.76	163	163
Insulin Receptor/Insulin/Shc	0	0.001	-10000	0	-10000	0	0
RHOA	0.013	0.003	-10000	0	-10000	0	0
LEPR	0.003	0.087	-10000	0	-0.67	7	7
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.12	0.19	-10000	0	-0.5	49	49
PRL	0.001	0.016	-10000	0	-0.31	1	1
SOCS3	-0.071	0.35	-10000	0	-1.5	27	27
SPRY2	0.009	0.057	-10000	0	-0.83	2	2
Insulin Receptor/Insulin/IRS1	-0.064	0.18	-10000	0	-0.56	55	55
CSF1/CSF1R	-0.009	0.095	-10000	0	-0.51	10	10
Ras protein signal transduction	0.02	0.023	-10000	0	-10000	0	0
IRS1	-0.082	0.27	-10000	0	-0.82	55	55
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.007	0.066	-10000	0	-0.31	21	21
STAT5B	-0.007	0.069	-10000	0	-0.3	5	5
STAT5A	-0.007	0.069	-10000	0	-0.3	5	5
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.069	-10000	0	-0.36	4	4
CSN2	-0.007	0.055	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
LAT	0.002	0.066	-10000	0	-0.54	5	5
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.01	0.11	-10000	0	-0.44	25	25
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.13	0.16	-10000	0	-0.31	211	211

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.003	0.041	-10000	0	-0.63	2	2
Necdin/E2F1	-0.069	0.12	-10000	0	-0.76	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.036	0.1	-10000	0	-0.49	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.29	0.28	-10000	0	-0.57	228	228
NT-4/5 (dimer)/p75(NTR)	-0.075	0.18	-10000	0	-0.67	35	35
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.005	0.12	-10000	0	-0.49	23	23
IKBKG	0.013	0	-10000	0	-10000	0	0
BDNF	-0.014	0.14	-10000	0	-0.6	21	21
MGDIs/NGR/p75(NTR)/LINGO1	-0.05	0.12	-10000	0	-0.54	21	21
FURIN	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.058	0.14	-10000	0	-0.55	31	31
LINGO1	-0.004	0.072	-10000	0	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.026	-10000	0	-10000	0	0
proBDNF (dimer)	-0.014	0.14	-10000	0	-0.6	21	21
NTRK1	-0.002	0.062	-10000	0	-0.31	18	18
RTN4R	0.013	0	-10000	0	-10000	0	0
neuron apoptosis	-0.011	0.13	-10000	0	-0.49	24	24
IRAK1	0.013	0	-10000	0	-10000	0	0
SHC1	-0.022	0.13	-10000	0	-0.57	20	20
ARHGDIA	0.013	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.04	0.11	-10000	0	-0.52	20	20
MAGEH1	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.045	0.12	-10000	0	-0.52	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.5	25	25
proNGF (dimer)	0.006	0.07	-10000	0	-0.57	6	6
MAGED1	0.013	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.021	0.16	-10000	0	-0.64	25	25
ZNF274	0.013	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.038	0.1	-10000	0	-0.49	20	20
NGF	0.006	0.071	-10000	0	-0.57	6	6
cell cycle arrest	0.042	0.16	-10000	0	-0.47	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.087	-10000	0	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.065	0.16	-10000	0	-0.59	36	36
NCSTN	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.047	0.12	-10000	0	-0.57	21	21
PSENEN	0.013	0	-10000	0	-10000	0	0
mol:ceramide	-0.011	0.12	-10000	0	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.071	-10000	0	-0.44	2	2
p75(NTR)/beta APP	-0.051	0.13	-10000	0	-0.63	18	18
BEX1	-0.36	0.42	-10000	0	-0.82	213	213
mol:GDP	-0.032	0.13	-10000	0	-0.58	20	20
NGF (dimer)	-0.095	0.13	-10000	0	-0.51	30	30
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.043	0.11	-10000	0	-0.52	18	18
PIK3R1	0.013	0	-10000	0	-10000	0	0
RAC1/GTP	-0.039	0.11	-10000	0	-0.5	20	20
MYD88	0.013	0	-10000	0	-10000	0	0
CHUK	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.047	0.13	-10000	0	-0.57	21	21
RHOB	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.063	0.093	-10000	0	-10000	0	0
NT3 (dimer)	-0.05	0.2	-10000	0	-0.62	48	48
TP53	-0.006	0.13	-10000	0	-0.45	31	31
PRDM4	-0.011	0.12	-10000	0	-0.52	20	20
BDNF (dimer)	-0.13	0.16	-10000	0	-0.54	39	39
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
SORT1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.036	0.1	-10000	0	-0.48	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.042	0.12	-10000	0	-0.52	22	22
RHOC	0.013	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
MAPK10	0.022	0.12	-10000	0	-0.45	20	20
DIABLO	0.013	0	-10000	0	-10000	0	0
SMPD2	-0.011	0.12	-10000	0	-0.52	20	20
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.046	0.12	-10000	0	-0.57	20	20
PSEN1	0.013	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.029	-10000	0	-0.63	1	1
NT3 (dimer)/p75(NTR)	-0.096	0.2	-10000	0	-0.66	46	46
MAPK8	0.017	0.13	-10000	0	-0.46	20	20
MAPK9	0.023	0.12	-10000	0	-0.44	19	19
APAF1	0.012	0.038	-10000	0	-0.82	1	1
NTF3	-0.05	0.21	-10000	0	-0.62	48	48
NTF4	-0.021	0.16	-10000	0	-0.64	25	25
NDN	0.005	0.085	-10000	0	-0.82	5	5
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.033	0.097	-10000	0	-0.45	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.055	-10000	0	-0.66	3	3
RhoA-B-C/GTP	-0.047	0.12	-10000	0	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.049	0.12	-10000	0	-0.48	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.053	0.13	-10000	0	-0.52	31	31
PRKACB	0.012	0.038	-10000	0	-0.82	1	1
proBDNF (dimer)/p75 ECD	-0.022	0.11	-10000	0	-0.63	14	14
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.68	35	35
BIRC2	0.013	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.065	0.17	0.24	183	-0.47	20	203
BAD	0.029	0.12	-10000	0	-0.44	20	20
RIPK2	0.013	0	-10000	0	-10000	0	0
NGFR	-0.063	0.19	-10000	0	-0.42	84	84
CYCS	-0.002	0.12	-10000	0	-0.48	20	20
ADAM17	0.01	0.054	-10000	0	-0.82	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.042	0.12	-10000	0	-0.52	22	22
BCL2L11	0.029	0.12	-10000	0	-0.44	20	20
BDNF (dimer)/p75(NTR)	-0.07	0.17	-10000	0	-0.63	31	31
PI3K	-0.043	0.12	-10000	0	-0.53	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.04	0.11	-10000	0	-0.52	20	20
NDNL2	0.013	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.056	0.14	-10000	0	-0.66	20	20
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.04	0.11	-10000	0	-0.52	20	20
TRAF6	0.01	0.054	-10000	0	-0.82	2	2
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
PLG	-0.003	0.035	-10000	0	-0.31	6	6
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.018	0.14	-10000	0	-0.49	31	31
SQSTM1	0.013	0	-10000	0	-10000	0	0
NGFRAP1	0.013	0	-10000	0	-10000	0	0
CASP3	0.03	0.11	-10000	0	-0.4	20	20
E2F1	-0.088	0.15	-10000	0	-0.31	150	150
CASP9	0.013	0	-10000	0	-10000	0	0
IKK complex	-0.014	0.059	-10000	0	-0.54	3	3
NGF (dimer)/TRKA	-0.013	0.064	-10000	0	-0.64	3	3
MMP7	-0.18	0.22	-10000	0	-0.37	240	240
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-10000	0	-0.49	22	22
MMP3	-0.038	0.11	-10000	0	-0.31	66	66
APAF-1/Caspase 9	-0.041	0.11	-10000	0	-0.61	7	7

×

Fc-epsilon receptor I signaling in mast cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.015	-9999	-0.31	1	1
LAT2	-0.019	0.1	-9999	-0.4	4	4
AP1	-0.21	0.28	-9999	-0.57	162	162
mol:PIP3	-0.018	0.15	-9999	-0.52	14	14
IKBKB	0.002	0.094	-9999	-0.28	15	15
AKT1	-0.019	0.14	-9999	-0.59	6	6
IKBKG	0.002	0.094	-9999	-0.28	15	15
MS4A2	-0.067	0.14	-9999	-0.31	113	113
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.83	3	3
MAP3K1	0.009	0.1	-9999	-0.47	7	7
mol:Ca2+	-0.009	0.12	-9999	-0.38	14	14
LYN	0.01	0.007	-9999	-10000	0	0
CBLB	-0.011	0.09	-9999	-0.36	3	3
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.082	0.19	-9999	-0.5	78	78
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	24	24
PLD2	-0.05	0.15	-9999	-0.45	42	42
PTPN13	-0.002	0.1	-9999	-0.59	5	5
PTPN11	0.011	0.04	-9999	-0.86	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.017	0.1	-9999	-0.36	5	5
SYK	0.01	0.007	-9999	-10000	0	0
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.064	0.13	-9999	-0.54	14	14
LAT	-0.016	0.1	-9999	-0.43	8	8
PAK2	0	0.11	-9999	-0.51	8	8
NFATC2	-0.15	0.28	-9999	-0.76	83	83
HRAS	-0.009	0.12	-9999	-0.54	9	9
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.031	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.17	-9999	-0.47	71	71
Antigen/IgE/Fc epsilon R1	-0.093	0.16	-9999	-0.43	71	71
mol:GDP	-0.017	0.13	-9999	-0.5	15	15
JUN	-0.18	0.35	-9999	-0.82	109	109
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	128	128
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.045	0.08	-9999	-0.38	4	4
CHUK	0.002	0.094	-9999	-0.29	13	13
KLRG1	-0.023	0.11	-9999	-0.41	14	14
VAV1	-0.024	0.12	-9999	-0.49	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.011	0.09	-9999	-0.35	4	4
negative regulation of mast cell degranulation	-0.021	0.11	-9999	-0.39	12	12
BTK	-0.048	0.11	-9999	-0.59	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.05	0.19	-9999	-0.5	49	49
GAB2/PI3K/SHP2	-0.067	0.13	-9999	-0.63	7	7
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.02	0.096	-9999	-0.29	36	36
RAF1	0.018	0.021	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.2	-9999	-0.58	57	57
FCER1G	-0.009	0.083	-9999	-0.32	32	32
FCER1A	-0.079	0.23	-9999	-0.56	76	76
Antigen/IgE/Fc epsilon R1/Fyn	-0.083	0.14	-9999	-0.48	43	43
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.006	0.1	-9999	-0.69	9	9
DUSP1	-0.12	0.31	-9999	-0.82	78	78
NF-kappa-B/RelA	-0.02	0.044	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.006	0.085	-9999	-0.38	1	1
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.043	0.1	-9999	-0.55	10	10
FER	-0.014	0.099	-9999	-0.43	7	7
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.074	0.18	-9999	-0.53	60	60
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.013	0.13	-9999	-0.57	10	10
cytokine secretion	-0.014	0.032	-9999	-0.22	1	1
SPHK1	-0.015	0.094	-9999	-0.45	2	2
PTK2	-0.006	0.087	-9999	-0.39	1	1
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.067	0.14	-9999	-0.56	12	12
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.012	0.15	-9999	-0.5	13	13
MAP2K2	0.025	0.018	-9999	-10000	0	0
MAP2K1	0.025	0.018	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.049	0.095	-9999	-0.42	14	14
MAP2K4	0.021	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.21	-9999	-0.62	54	54
mol:Choline	-0.05	0.15	-9999	-0.44	42	42
SHC/Grb2/SOS1	-0.032	0.067	-9999	-0.4	1	1
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.002	0.082	-9999	-0.36	1	1
HCLS1	-0.013	0.094	-9999	-0.38	5	5
PRKCB	-0.012	0.12	-9999	-0.38	22	22
FCGR2B	-0.029	0.18	-9999	-0.75	27	27
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.022	0.11	-9999	-0.4	12	12
LCP2	0.008	0.039	-9999	-0.32	7	7
PLA2G4A	-0.043	0.16	-9999	-0.52	35	35
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.05	0.15	-9999	-0.44	42	42
IKK complex	0.017	0.076	-9999	-0.22	5	5
WIPF1	0.013	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.038	-9999	-0.82	1	1
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.67	15	15
PTK2	-0.039	0.15	-9999	-0.6	28	28
positive regulation of JNK cascade	-0.02	0.081	-9999	-0.34	28	28
CDC42/GDP	0.031	0.13	-9999	-0.47	28	28
Rac1/GDP	0.033	0.12	-9999	-0.46	28	28
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.025	0.1	-9999	-0.43	28	28
nectin-3/I-afadin	-0.037	0.15	-9999	-0.63	28	28
RAPGEF1	0.024	0.14	-9999	-0.54	28	28
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0.16	-9999	-0.63	28	28
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
TLN1	0.019	0.075	-9999	-0.94	1	1
Rap1/GTP	-0.022	0.086	-9999	-0.37	28	28
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.037	0.15	-9999	-0.63	28	28
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.025	0.16	-9999	-0.59	28	28
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PI3K	-0.031	0.13	-9999	-0.51	29	29
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.033	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.021	0.085	-9999	-0.36	28	28
PVRL1	0.005	0.053	-9999	-0.31	13	13
PVRL3	-0.035	0.2	-9999	-0.82	28	28
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
CLDN1	-0.26	0.15	-9999	-0.33	393	393
JAM-A/CLDN1	-0.14	0.14	-9999	-0.58	38	38
SRC	-0.043	0.17	-9999	-0.72	28	28
ITGB3	-0.011	0.14	-9999	-0.82	14	14
nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.033	-9999	-10000	0	0
FARP2	0.019	0.15	-9999	-0.58	28	28
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.032	0.13	-9999	-0.55	28	28
nectin-1/I-afadin	-0.005	0.033	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.036	0.13	-9999	-0.55	28	28
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.02	0.081	-9999	-0.34	28	28
alphaV/beta3 Integrin/Talin	0.018	0.13	-9999	-0.6	15	15
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0.011	0.08	-9999	-1	1	1
VAV2	0.018	0.15	-9999	-0.59	28	28
RAP1/GDP	-0.026	0.1	-9999	-0.43	28	28
ITGAV	0.01	0.054	-9999	-0.82	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.032	0.13	-9999	-0.55	28	28
nectin-3(dimer)/I-afadin/I-afadin	-0.037	0.15	-9999	-0.63	28	28
Rac1/GTP	-0.026	0.1	-9999	-0.44	28	28
PTPRM	-0.019	0.082	-9999	-0.32	28	28
E-cadherin/beta catenin/alpha catenin	-0.003	0.016	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.077	-9999	-0.74	5	5
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.58	15	15
PTK2	0.016	0.15	-9999	-0.54	16	16
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.025	0.1	-9999	-0.31	56	56
SRC	0.013	0.015	-9999	-0.31	1	1
CDKN1B	-0.064	0.18	-9999	-0.61	46	46
VEGFA	0.008	0.066	-9999	-0.82	3	3
ILK	-0.064	0.18	-9999	-0.61	45	45
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.059	0.17	-9999	-0.57	45	45
PTK2B	0.02	0.11	-9999	-0.51	20	20
alphaV/beta3 Integrin/JAM-A	-0.06	0.16	-9999	-0.48	59	59
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.019	0.1	-9999	-0.58	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.26	-9999	-0.54	155	155
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.003	0.11	-9999	-0.54	3	3
alphaV/beta3 Integrin/Syndecan-1	-0.019	0.1	-9999	-0.58	15	15
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.24	0.25	-9999	-0.62	114	114
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
alphaV/beta3 Integrin/Osteopontin	-0.071	0.16	-9999	-0.57	37	37
RPS6KB1	-0.21	0.24	-9999	-0.57	114	114
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.095	0.15	-9999	-0.75	15	15
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.095	0.15	-9999	-0.75	15	15
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.035	0.15	-9999	-0.62	27	27
cell adhesion	-0.029	0.099	-9999	-0.54	15	15
ANGPTL3	0.005	0.026	-9999	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.069	-9999	-0.64	5	5
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.008	0.066	-9999	-0.82	3	3
ITGB3	-0.011	0.14	-9999	-0.82	14	14
IGF1	-0.18	0.35	-9999	-0.8	118	118
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.1	-9999	-0.58	15	15
apoptosis	0.01	0.054	-9999	-0.82	2	2
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.018	0.1	-9999	-0.58	15	15
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.038	0.14	-9999	-0.61	22	22
CSF1	-0.001	0.11	-9999	-0.82	8	8
PIK3C2A	-0.066	0.18	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.054	0.14	-9999	-0.78	3	3
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.023	0.11	-9999	-0.55	20	20
FAK1/Vinculin	0.024	0.13	-9999	-0.48	8	8
alphaV beta3/Integrin/ppsTEM5	-0.018	0.1	-9999	-0.58	15	15
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.07	0.24	-9999	-0.76	52	52
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	0.013	0	-9999	-10000	0	0
F11R	0.024	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	-0.036	0.11	-9999	-0.58	15	15
alphaV/beta3 Integrin/TGFBR2	-0.021	0.12	-9999	-0.6	17	17
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.01	0.077	-9999	-0.55	9	9
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.017	0.096	-9999	-0.54	15	15
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	-0.021	0.1	-9999	-0.51	20	20
SDC1	0.011	0.03	-9999	-0.31	4	4
VAV3	0.026	0.1	-9999	-0.53	14	14
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.082	0.27	-9999	-0.82	55	55
FAK1/Paxillin	0.024	0.13	-9999	-0.48	8	8
cell migration	0.034	0.12	-9999	-0.43	8	8
ITGAV	0.01	0.054	-9999	-0.82	2	2
PI3K	-0.056	0.15	-9999	-0.44	60	60
SPP1	-0.083	0.2	-9999	-0.42	108	108
KDR	0.008	0.066	-9999	-0.82	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.054	-9999	-0.82	2	2
COL4A3	-0.013	0.14	-9999	-0.82	15	15
angiogenesis	-0.084	0.18	-9999	-0.59	36	36
Rac1/GTP	-0.014	0.084	-9999	-0.48	14	14
EDIL3	-0.023	0.14	-9999	-0.43	40	40
cell proliferation	-0.021	0.12	-9999	-0.6	17	17

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.009	0.22	-10000	0	-0.96	21	21
NCK1/PAK1/Dok-R	-0.029	0.091	-10000	0	-0.43	21	21
NCK1/Dok-R	-0.069	0.24	-10000	0	-1.2	21	21
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
mol:beta2-estradiol	-0.003	0.048	0.25	15	-10000	0	15
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.014	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.01	0.069	-10000	0	-0.33	11	11
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.061	0.23	-10000	0	-1.1	21	21
FN1	-0.22	0.15	-10000	0	-10000	0	0
PLD2	-0.001	0.28	-10000	0	-1.2	21	21
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GRB14	-0.009	0.14	-10000	0	-0.82	13	13
ELK1	0.015	0.24	-10000	0	-1.1	21	21
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.25	-10000	0	-1.2	21	21
CDKN1A	-0.012	0.17	-10000	0	-0.64	21	21
ITGA5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.069	0.24	-10000	0	-1.2	21	21
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.026	0.17	-10000	0	-0.69	21	21
PLG	-0.01	0.28	-10000	0	-1.2	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.008	0.21	-10000	0	-0.92	21	21
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
ANGPT2	-0.11	0.22	-10000	0	-0.76	22	22
BMX	-0.015	0.29	-10000	0	-1.3	21	21
ANGPT1	-0.04	0.3	-10000	0	-1.5	18	18
tube development	-0.018	0.19	-10000	0	-0.73	21	21
ANGPT4	-0.06	0.23	-10000	0	-0.75	47	47
response to hypoxia	0	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.019	0.3	-10000	0	-1.3	21	21
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.021	0.21	-10000	0	-0.84	21	21
mol:L-citrulline	0.026	0.17	-10000	0	-0.69	21	21
AGTR1	-0.32	0.41	-10000	0	-0.82	194	194
MAPK14	-0.012	0.27	-10000	0	-1.2	21	21
Tie2/SHP2	-0.025	0.15	-10000	0	-1.4	5	5
TEK	0.015	0.17	-10000	0	-1.5	5	5
RPS6KB1	0.009	0.21	-10000	0	-0.92	21	21
Angiotensin II/AT1	-0.25	0.32	-10000	0	-0.64	194	194
Tie2/Ang1/GRB2	-0.006	0.28	-10000	0	-1.3	21	21
MAPK3	0.01	0.25	-10000	0	-1.1	21	21
MAPK1	0.01	0.25	-10000	0	-1.1	21	21
Tie2/Ang1/GRB7	-0.03	0.29	-10000	0	-1.3	21	21
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MAPK8	-0.009	0.29	-10000	0	-1.2	22	22
PI3K	-0.006	0.26	-10000	0	-1.1	21	21
FES	-0.012	0.27	-10000	0	-1.2	21	21
Crk/Dok-R	-0.069	0.24	-10000	0	-1.2	21	21
Tie2/Ang1/ABIN2	-0.006	0.28	-10000	0	-1.3	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.014	0.2	-10000	0	-0.84	21	21
STAT5A	0.014	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.009	0.21	-10000	0	-0.92	21	21
Tie2/Ang2	-0.041	0.24	-10000	0	-1	21	21
Tie2/Ang1	-0.013	0.3	-10000	0	-1.4	21	21
FOXO1	0.021	0.2	-10000	0	-0.85	21	21
ELF1	0.015	0.079	-10000	0	-0.85	4	4
ELF2	-0.004	0.27	-10000	0	-1.2	21	21
mol:Choline	0.002	0.26	-10000	0	-1.2	21	21
cell migration	-0.024	0.056	-10000	0	-0.24	21	21
FYN	-0.024	0.21	-10000	0	-0.84	21	21
DOK2	0	0.076	-10000	0	-0.38	16	16
negative regulation of cell cycle	-0.008	0.16	-10000	0	-0.58	21	21
ETS1	0.015	0.045	-10000	0	-10000	0	0
PXN	0.022	0.18	-10000	0	-0.74	21	21
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.022	0.19	-10000	0	-0.79	21	21
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.09	0.28	-10000	0	-0.83	58	58
MAPKKK cascade	0.002	0.26	-10000	0	-1.2	21	21
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.01	0.28	-10000	0	-1.3	21	21
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.028	0.15	-10000	0	-0.61	21	21
mol:Phosphatidic acid	0.002	0.26	-10000	0	-1.2	21	21
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.026	0.17	-10000	0	-0.69	21	21
Rac1/GTP	-0.052	0.18	-10000	0	-0.85	21	21
MMP2	-0.008	0.28	-10000	0	-1.3	21	21

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.047	0.35	-9999	-0.92	14	14
PLK1	0.044	0.07	-9999	-10000	0	0
BIRC5	0.024	0.12	-9999	-1.6	1	1
HSPA1B	0.047	0.35	-9999	-0.92	14	14
MAP2K1	0.032	0.038	-9999	-10000	0	0
BRCA2	0.042	0.36	-9999	-0.98	17	17
FOXM1	0.035	0.39	-9999	-1	19	19
XRCC1	0.047	0.35	-9999	-0.92	14	14
FOXM1B/p19	-0.097	0.31	-9999	-0.9	26	26
Cyclin D1/CDK4	0.034	0.34	-9999	-0.86	14	14
CDC2	0.04	0.37	-9999	-0.91	19	19
TGFA	0.017	0.35	-9999	-0.85	17	17
SKP2	0.04	0.37	-9999	-0.98	17	17
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.047	0.35	-9999	-0.92	14	14
RB1	-0.054	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.031	0.37	-9999	-1	18	18
AURKB	-0.003	0.12	-9999	-10000	0	0
CENPF	0.042	0.36	-9999	-0.95	14	14
CDK4	0.019	0.015	-9999	-10000	0	0
MYC	0.039	0.36	-9999	-0.92	21	21
CHEK2	0.032	0.038	-9999	-10000	0	0
ONECUT1	0.031	0.35	-9999	-0.89	16	16
CDKN2A	-0.13	0.16	-9999	-0.31	206	206
LAMA4	0.047	0.35	-9999	-0.92	14	14
FOXM1B/HNF6	0.023	0.37	-9999	-1	16	16
FOS	-0.19	0.66	-9999	-1.2	129	129
SP1	0.014	0.005	-9999	-10000	0	0
CDC25B	0.046	0.35	-9999	-0.92	14	14
response to radiation	0.015	0.035	-9999	-10000	0	0
CENPB	0.047	0.35	-9999	-0.92	14	14
CENPA	0.034	0.37	-9999	-0.96	19	19
NEK2	0.037	0.36	-9999	-0.95	16	16
HIST1H2BA	0.038	0.35	-9999	-0.92	14	14
CCNA2	0.01	0.047	-9999	-0.33	9	9
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.035	0.38	-9999	-1	14	14
CCNB2	0.044	0.36	-9999	-0.95	14	14
CCNB1	0.042	0.37	-9999	-0.96	14	14
ETV5	0.046	0.35	-9999	-0.92	15	15
ESR1	-0.002	0.44	-9999	-1.1	35	35
CCND1	0.037	0.34	-9999	-0.88	14	14
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.05	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.017	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.13	0.23	-9999	-0.88	22	22
GAS1	-0.13	0.61	-9999	-1.2	104	104
MMP2	0.037	0.38	-9999	-1.2	16	16
RB1/FOXM1C	0.045	0.34	-9999	-0.93	14	14
CREBBP	0.013	0	-9999	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.012	0.093	-10000	0	-0.35	6	6
epithelial cell differentiation	-0.047	0.1	-10000	0	-0.47	10	10
ITCH	0.024	0.02	-10000	0	-10000	0	0
WWP1	0	0.079	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.006	0.076	-10000	0	-0.82	4	4
PRL	0.001	0.015	-10000	0	-0.31	1	1
neuron projection morphogenesis	0.004	0.14	-10000	0	-0.51	10	10
PTPRZ1	-0.016	0.13	-10000	0	-0.56	23	23
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.058	0.13	-10000	0	-0.45	46	46
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.043	0.17	-10000	0	-0.53	47	47
ADAM17	0.02	0.058	-10000	0	-0.82	2	2
ErbB4/ErbB4	-0.01	0.1	-10000	0	-0.52	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.045	0.17	-10000	0	-0.56	37	37
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.067	0.15	-10000	0	-0.5	46	46
GRIN2B	-0.029	0.16	-10000	0	-0.47	46	46
ErbB4/ErbB2/betacellulin	-0.036	0.11	-10000	0	-0.63	13	13
STAT1	0.006	0.049	-10000	0	-0.31	11	11
HBEGF	-0.004	0.072	-10000	0	-0.31	25	25
PRLR	-0.046	0.2	-10000	0	-0.6	46	46
E4ICDs/ETO2	-0.005	0.091	-10000	0	-0.49	3	3
axon guidance	-0.001	0.087	-10000	0	-0.39	5	5
NEDD4	0.02	0.057	-10000	0	-0.81	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.044	0.15	-10000	0	-0.64	26	26
CBFA2T3	0.011	0.041	-10000	0	-0.57	2	2
ErbB4/ErbB2/HBEGF	-0.029	0.061	-10000	0	-0.58	2	2
MAPK3	-0.005	0.15	-10000	0	-0.54	10	10
STAT1 (dimer)	-0.007	0.09	-10000	0	-0.35	5	5
MAPK1	-0.005	0.15	-10000	0	-0.53	11	11
JAK2	0.012	0.038	-10000	0	-0.82	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.067	0.15	-10000	0	-0.5	46	46
NRG1	-0.035	0.2	-10000	0	-0.65	46	46
NRG3	-0.049	0.22	-10000	0	-0.82	36	36
NRG2	-0.083	0.26	-10000	0	-0.8	57	57
NRG4	0.008	0.036	-10000	0	-0.31	6	6
heart development	-0.001	0.087	-10000	0	-0.39	5	5
neural crest cell migration	-0.033	0.16	-10000	0	-0.49	46	46
ERBB2	0.028	0.043	-10000	0	-0.62	2	2
WWOX/E4ICDs	-0.005	0.093	-10000	0	-0.95	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.036	0.084	-10000	0	-0.66	4	4
apoptosis	0.057	0.14	0.46	37	-10000	0	37
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.066	0.19	-10000	0	-0.55	56	56
ErbB4/ErbB2/epiregulin	-0.078	0.088	-10000	0	-0.55	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.018	0.14	-10000	0	-0.65	14	14
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.06	0.12	-10000	0	-0.47	27	27
MDM2	0.001	0.087	-10000	0	-0.46	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.062	0.15	-10000	0	-0.5	46	46
STAT5A	0.008	0.082	-10000	0	-0.41	3	3
ErbB4/EGFR/neuregulin 1 beta	-0.071	0.16	-10000	0	-0.52	49	49
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.032	0.063	-10000	0	-0.43	1	1
STAT5A (dimer)	-0.05	0.11	-10000	0	-0.51	10	10
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.08	-10000	0	-0.41	3	3
LRIG1	-0.001	0.11	-10000	0	-0.82	8	8
EREG	-0.14	0.16	-10000	0	-0.31	224	224
BTC	-0.009	0.14	-10000	0	-0.82	13	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.087	-10000	0	-0.4	5	5
ERBB4	-0.01	0.1	-10000	0	-0.52	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.01	0.02	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.025	0.056	-10000	0	-0.51	2	2
glial cell differentiation	0.032	0.063	0.42	1	-10000	0	1
WWOX	0.012	0.038	-10000	0	-0.82	1	1
cell proliferation	-0.023	0.17	-10000	0	-0.46	53	53

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.018	0.087	-9999	-0.48	16	16
RGS9BP	-0.037	0.2	-9999	-0.82	29	29
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.067	0.25	-9999	-0.81	47	47
mol:Na +	-0.021	0.057	-9999	-10000	0	0
mol:ADP	-0.045	0.19	-9999	-0.64	46	46
GNAT2	0.009	0.022	-9999	-0.31	2	2
RGS9-1/Gbeta5/R9AP	-0.092	0.21	-9999	-0.56	79	79
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.011	-9999	-10000	0	0
GRK7	0.007	0.007	-9999	-10000	0	0
CNGB3	0.003	0.005	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.014	0.062	-9999	-0.3	2	2
Cone PDE6	-0.08	0.18	-9999	-0.49	79	79
Cone Metarhodopsin II	-0.05	0.15	-9999	-0.52	46	46
Na + (4 Units)	-0.025	0.057	-9999	-0.3	2	2
GNAT2/GDP	-0.08	0.18	-9999	-0.48	79	79
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.015	-9999	-10000	0	0
Cone Transducin	-0.019	0.092	-9999	-0.5	16	16
SLC24A2	-0.009	0.064	-9999	-0.31	20	20
GNB3/GNGT2	-0.023	0.11	-9999	-0.63	16	16
GNB3	-0.013	0.15	-9999	-0.79	16	16
GNAT2/GTP	-0.001	0.014	-9999	-0.21	2	2
CNGA3	-0.027	0.11	-9999	-0.31	59	59
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.057	-9999	-10000	0	0
mol:Pi	-0.092	0.21	-9999	-0.56	79	79
Cone CNG Channel	-0.016	0.043	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.009	0.064	-9999	-0.31	20	20
RGS9	-0.078	0.26	-9999	-0.8	54	54
PDE6C	0.003	0.016	-9999	-0.31	1	1
GNGT2	0.01	0.046	-9999	-0.44	4	4
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.004	0.006	-9999	-10000	0	0

×

Aurora C signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0.054	-9999	-0.82	2	2
Aurora C/Aurora B/INCENP	-0.039	0.077	-9999	-0.65	2	2
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.01	0.02	-9999	-10000	0	0
AURKB	-0.058	0.14	-9999	-0.31	105	105
AURKC	-0.001	0.067	-9999	-0.31	21	21

×

IL1-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.03	0.068	-9999	-0.32	8	8
IRAK/TOLLIP	0.029	0.004	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.25	-9999	-0.67	74	74
IL1A	-0.056	0.23	-9999	-0.79	41	41
IL1B	-0.034	0.19	-9999	-0.64	40	40
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-0.43	2	2
IL1R2	-0.082	0.24	-9999	-0.59	76	76
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.069	-9999	-0.3	1	1
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.004	0.085	-9999	-0.82	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.067	0.028	-9999	-10000	0	0
JUN	-0.073	0.22	-9999	-0.43	120	120
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.068	0.14	-9999	-0.47	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.074	0.14	-9999	-0.51	38	38
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.067	0.13	-9999	-0.48	38	38
IL1 beta fragment/IL1R1/IL1RAP	-0.078	0.15	-9999	-0.53	39	39
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.021	0.11	-9999	-0.52	17	17
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.045	0.12	-9999	-0.63	11	11
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
PI3K	-0.004	0.05	-9999	-0.63	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.088	-9999	-0.34	8	8
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.078	0.15	-9999	-0.53	39	39
IL1 beta/IL1R2	-0.1	0.23	-9999	-0.61	73	73
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.028	-9999	-0.44	2	2
NF kappa B1 p50/RelA	-0.058	0.12	-9999	-0.55	8	8
IRAK3	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.07	0.14	-9999	-0.48	44	44
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.016	0.1	-9999	-0.34	38	38
IL1 alpha/IL1R1/IL1RAP	-0.085	0.16	-9999	-0.56	38	38
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.022	0.035	-9999	-0.47	2	2
IL1RAP	-0.072	0.14	-9999	-0.31	126	126
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.054	0.12	-9999	-0.5	12	12
CASP1	0.008	0.06	-9999	-0.52	5	5
IL1RN/IL1R2	-0.11	0.22	-9999	-0.63	60	60
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.07	0.14	-9999	-0.5	39	39
TMEM189-UBE2V1	0.004	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.082	-9999	-0.34	4	4
PIK3CA	0.008	0.066	-9999	-0.82	3	3
IL1RN	-0.055	0.17	-9999	-0.38	84	84
TRAF6/TAK1/TAB1/TAB2	-0.002	0.03	-9999	-0.46	2	2
MAP2K6	0.022	0.074	-9999	-0.44	12	12

×

Regulation of nuclear SMAD2/3 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
EP300	0.02	0.015	-10000	0	-10000	0	0
HSPA8	0.004	0.076	-10000	0	-0.82	4	4
SMAD3/SMAD4/ER alpha	-0.052	0.14	-10000	0	-0.58	24	24
AKT1	0.008	0.011	-10000	0	-10000	0	0
GSC	-0.21	0.56	-10000	0	-1.6	71	71
NKX2-5	0.002	0.029	-10000	0	-0.31	4	4
muscle cell differentiation	0.026	0.051	0.44	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.005	0.08	-10000	0	-10000	0	0
SMAD4	-0.012	0.06	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.078	-10000	0	-0.55	5	5
SMAD3/SMAD4/VDR	0.01	0.044	-10000	0	-10000	0	0
MYC	0	0.14	-10000	0	-0.82	13	13
CDKN2B	-0.076	0.14	-10000	0	-10000	0	0
AP1	-0.26	0.51	-10000	0	-0.94	151	151
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.056	-10000	0	-0.71	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.063	-10000	0	-10000	0	0
SP3	0.016	0.002	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.012	0.074	-10000	0	-0.31	21	21
SMAD3/SMAD4/GR	-0.017	0.045	-10000	0	-10000	0	0
GATA3	-0.032	0.19	-10000	0	-0.78	27	27
SKI/SIN3/HDAC complex/NCoR1	0.04	0.03	-10000	0	-10000	0	0
MEF2C/TIF2	-0.046	0.17	-10000	0	-0.59	22	22
endothelial cell migration	-0.009	0.1	1.4	1	-10000	0	1
MAX	0.013	0.006	-10000	0	-10000	0	0
RBBP7	0.012	0.004	-10000	0	-10000	0	0
RBBP4	0.007	0.066	-10000	0	-0.82	3	3
RUNX2	-0.076	0.15	-10000	0	-0.32	128	128
RUNX3	-0.007	0.12	-10000	0	-0.6	16	16
RUNX1	-0.13	0.16	-10000	0	-0.31	211	211
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.006	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-0.31	1	1
CDKN1A	0.023	0.073	-10000	0	-10000	0	0
KAT2B	0.016	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.039	0.094	-10000	0	-0.48	2	2
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.012	0.004	-10000	0	-10000	0	0
SERPINE1	0.008	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.039	0.12	-10000	0	-0.59	18	18
SMAD3/SMAD4/ATF3	-0.16	0.26	-10000	0	-0.63	113	113
SAP30	0.01	0.038	-10000	0	-0.83	1	1
Cbp/p300/PIAS3	0.033	0.045	-10000	0	-10000	0	0
JUN	-0.25	0.5	-10000	0	-0.93	151	151
SMAD3/SMAD4/IRF7	-0.017	0.045	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.002	0.092	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.066	0.095	0.46	4	-10000	0	4
DLX1	-0.032	0.19	-10000	0	-0.82	26	26
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.23	0.4	-10000	0	-0.89	128	128
SMAD3/SMAD4/Max	-0.017	0.045	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.006	0.042	-10000	0	-0.55	2	2
ZBTB17	0.021	0.012	-10000	0	-10000	0	0
LAMC1	0.026	0.053	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.017	0.044	-10000	0	-10000	0	0
IRF7	0.014	0.016	-10000	0	-10000	0	0
ESR1	-0.048	0.19	-10000	0	-0.53	54	54
HNF4A	-0.004	0.045	-10000	0	-0.31	10	10
MEF2C	0.003	0.099	-10000	0	-1	1	1
SMAD2-3/SMAD4	-0.032	0.055	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.025	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.016	0.024	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.018	0.01	-10000	0	-10000	0	0
SKIL	0.012	0.038	-10000	0	-0.82	1	1
HDAC1	0.012	0.004	-10000	0	-10000	0	0
HDAC2	0.012	0.004	-10000	0	-10000	0	0
SNIP1	0.008	0.054	-10000	0	-0.82	2	2
GCN5L2	0.006	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.012	0.045	-10000	0	-10000	0	0
MSG1/HSC70	-0.18	0.1	-10000	0	-0.68	9	9
SMAD2	-0.003	0.04	-10000	0	-10000	0	0
SMAD3	-0.005	0.047	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.075	-10000	0	-0.36	13	13
SMAD2/SMAD2/SMAD4	0.014	0.028	-10000	0	-10000	0	0
NCOR1	0.012	0.004	-10000	0	-10000	0	0
NCOA2	-0.063	0.24	-10000	0	-0.82	44	44
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.018	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.013	0.077	-10000	0	-10000	0	0
IFNB1	0.014	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.006	0.1	-10000	0	-1	1	1
CITED1	-0.26	0.14	-10000	0	-0.82	5	5
SMAD2-3/SMAD4/ARC105	-0.022	0.046	-10000	0	-10000	0	0
RBL1	-0.008	0.13	-10000	0	-0.82	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.006	0.081	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.081	0.11	-10000	0	-0.49	14	14
SMAD7	-0.1	0.28	-10000	0	-0.59	101	101
MYC/MIZ-1	0.013	0.11	-10000	0	-0.63	13	13
SMAD3/SMAD4	0.064	0.1	0.32	39	-0.35	1	40
IL10	-0.027	0.19	-10000	0	-0.62	38	38
PIASy/HDAC complex	0.007	0.01	-10000	0	-10000	0	0
PIAS3	0.016	0.005	-10000	0	-10000	0	0
CDK2	0.018	0.011	-10000	0	-10000	0	0
IL5	-0.016	0.14	-10000	0	-0.51	25	25
CDK4	0.019	0.012	-10000	0	-10000	0	0
PIAS4	0.007	0.01	-10000	0	-10000	0	0
ATF3	-0.19	0.35	-10000	0	-0.79	120	120
SMAD3/SMAD4/SP1	-0.016	0.054	-10000	0	-10000	0	0
FOXG1	-0.003	0.072	-10000	0	-0.39	13	13
FOXO3	0.017	0.015	-10000	0	-10000	0	0
FOXO1	0.017	0.015	-10000	0	-10000	0	0
FOXO4	0.017	0.015	-10000	0	-10000	0	0
heart looping	0.003	0.098	-10000	0	-1	1	1
CEBPB	0.009	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.049	0.14	-10000	0	-0.6	26	26
MYOD1	-0.002	0.029	-10000	0	-0.31	4	4
SMAD3/SMAD4/HNF4	-0.024	0.052	-10000	0	-0.4	1	1
SMAD3/SMAD4/GATA3	-0.052	0.14	-10000	0	-0.54	30	30
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.038	-10000	0	-0.82	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.075	0.11	-10000	0	-0.55	11	11
SMAD3/SMAD4/SP1-3	0.007	0.057	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.015	0.022	-10000	0	-10000	0	0
SIN3B	0.012	0.004	-10000	0	-10000	0	0
SIN3A	0.012	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.017	0.095	-10000	0	-0.52	2	2
ITGB5	0.036	0.059	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.042	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.26	0.29	-10000	0	-0.6	202	202
AR	-0.34	0.41	-10000	0	-0.82	202	202
negative regulation of cell growth	-0.04	0.13	-10000	0	-0.46	8	8
SMAD3/SMAD4/MYOD	-0.023	0.049	-10000	0	-10000	0	0
E2F5	0.012	0.038	-10000	0	-0.82	1	1
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.013	0.067	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.067	-10000	0	-10000	0	0
TFDP1	0.012	0.038	-10000	0	-0.82	1	1
SMAD3/SMAD4/AP1	-0.27	0.51	-10000	0	-0.96	151	151
SMAD3/SMAD4/RUNX2	-0.066	0.096	-10000	0	-0.47	4	4
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.018	0.16	-10000	0	-0.82	18	18

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.041	0.12	-9999	-0.42	46	46
Syndecan-3/Neurocan	-0.035	0.12	-9999	-0.47	35	35
POMC	-0.16	0.34	-9999	-0.81	102	102
EGFR	0.006	0.076	-9999	-0.82	4	4
Syndecan-3/EGFR	-0.004	0.043	-9999	-0.46	4	4
AGRP	-0.004	0.06	-9999	-0.31	17	17
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.013	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.051	0.22	-9999	-0.77	39	39
long-term memory	0	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.039	0.081	-9999	-0.46	10	10
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0	0.009	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	-0.001	0.008	-9999	-10000	0	0
MC4R	0.001	0.039	-9999	-0.31	7	7
SRC	0.013	0.015	-9999	-0.31	1	1
PTN	-0.067	0.25	-9999	-0.81	47	47
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	-0.069	0.15	-9999	-0.41	80	80
Syndecan-3/AgRP	-0.005	0.023	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.006	0.025	-9999	-10000	0	0
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.038	0.08	-9999	-0.46	10	10
IL8	-0.081	0.18	-9999	-0.36	123	123
Syndecan-3/Fyn/Cortactin	-0.001	0.006	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.14	0.26	-9999	-0.64	99	99
Gamma Secretase	0	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.25	0.39	-10000	0	-0.82	152	152
HRAS	0.012	0.021	-10000	0	-0.31	2	2
EGFR	0.006	0.076	-10000	0	-0.82	4	4
AKT	0.018	0.025	-10000	0	-10000	0	0
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.11	0.16	-10000	0	-0.31	179	179
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.011	0.13	-10000	0	-0.67	17	17
PIK3R3	0.012	0.038	-10000	0	-0.82	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.061	0.099	-10000	0	-0.26	43	43
ERBB2	0.013	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.024	0.024	0.19	1	-0.17	1	2
PI3K	-0.041	0.096	0.23	1	-0.22	50	51
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.024	0.027	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.001	0.078	-9999	-10000	0	0
STMN1	-0.02	0.093	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.025	0.11	-9999	-0.32	41	41
Chromosomal passenger complex/Cul3 protein complex	0.007	0.071	-9999	-0.29	14	14
BIRC5	-0.017	0.1	-9999	-0.33	42	42
DES	-0.38	0.3	-9999	-0.61	295	295
Aurora C/Aurora B/INCENP	-0.015	0.088	-9999	-0.65	2	2
Aurora B/TACC1	-0.02	0.08	-9999	-0.71	1	1
Aurora B/PP2A	-0.025	0.09	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.005	0.025	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.049	0.15	-9999	-0.39	59	59
Cul3 protein complex	-0.018	0.088	-9999	-0.55	12	12
KIF2C	0	0.042	-9999	-0.14	4	4
PEBP1	0.011	0.005	-9999	-10000	0	0
KIF20A	-0.041	0.12	-9999	-0.31	81	81
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.025	0.09	-9999	-10000	0	0
SEPT1	0.008	0.042	-9999	-0.31	8	8
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.007	0.045	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
H3F3B	-0.006	0.054	-9999	-10000	0	0
AURKB	-0.049	0.14	-9999	-0.31	105	105
AURKC	-0.001	0.067	-9999	-0.31	21	21
CDCA8	0.01	0.027	-9999	-0.33	3	3
cytokinesis	-0.066	0.082	-9999	-0.42	6	6
Aurora B/Septin1	-0.026	0.1	-9999	-0.44	7	7
AURKA	0.012	0.002	-9999	-10000	0	0
INCENP	0.009	0.055	-9999	-0.84	2	2
KLHL13	-0.017	0.14	-9999	-0.55	26	26
BUB1	-0.1	0.16	-9999	-0.32	167	167
hSgo1/Aurora B/Survivin	-0.026	0.12	-9999	-0.35	42	42
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.03	0.072	-9999	-0.35	4	4
SGOL1	0.001	0.062	-9999	-0.31	18	18
CENPA	-0.007	0.069	-9999	-0.21	26	26
NCAPG	-0.018	0.097	-9999	-0.31	47	47
Aurora B/HC8 Proteasome	-0.025	0.09	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.025	0.09	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.034	0.12	-9999	-0.31	70	70
NPM1	-0.011	0.048	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.013	0	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.09	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.035	0.08	-9999	-0.35	18	18
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.011	0.048	-9999	-10000	0	0
MYLK	-0.006	0.054	-9999	-10000	0	0
KIF23	-0.004	0.074	-9999	-0.32	25	25
VIM	-0.02	0.092	-9999	-10000	0	0
RACGAP1	0.013	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.011	0.048	-9999	-10000	0	0
Chromosomal passenger complex	-0.013	0.083	-9999	-0.25	26	26
Chromosomal passenger complex/EVI5	0.011	0.12	-9999	-0.48	6	6
TACC1	0.012	0.038	-9999	-0.82	1	1
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.004	0.076	-10000	0	-0.36	7	7
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.012	0.038	-10000	0	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.042	0.077	0.23	15	-0.28	10	25
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.066	0.23	-10000	0	-0.63	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.025	-10000	0	-0.55	1	1
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.03	0.11	-10000	0	-0.31	62	62
PRKCI	0.013	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.038	0.1	-10000	0	-10000	0	0
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	0.042	0.081	0.24	15	-0.3	10	25
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.028	0	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	310	310
LNPEP	-0.014	0.15	-10000	0	-0.82	16	16
YWHAE	0.013	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.065	0.082	-10000	0	-0.34	22	22
NT3 (dimer)/TRKC	-0.09	0.2	-10000	0	-0.68	40	40
NT3 (dimer)/TRKB	-0.086	0.18	-10000	0	-0.58	50	50
SHC/Grb2/SOS1/GAB1/PI3K	0.038	0.029	-10000	0	-0.33	3	3
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.014	0.14	-10000	0	-0.6	21	21
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.002	0.062	-10000	0	-0.31	18	18
NTRK2	0.005	0.085	-10000	0	-0.82	5	5
NTRK3	-0.056	0.17	-10000	0	-0.39	83	83
NT-4/5 (dimer)/TRKB	-0.068	0.16	-10000	0	-0.58	39	39
neuron apoptosis	0.04	0.092	0.42	15	-10000	0	15
SHC 2-3/Grb2	-0.043	0.1	-10000	0	-0.48	13	13
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.03	0.093	-10000	0	-0.64	6	6
SHC3	-0.047	0.1	-10000	0	-0.55	12	12
STAT3 (dimer)	0.018	0.024	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.087	0.18	-10000	0	-0.57	48	48
RIN/GDP	-0.01	0.063	-10000	0	-0.28	2	2
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.033	0.093	-10000	0	-0.42	23	23
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.026	0.044	-10000	0	-10000	0	0
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.021	0.16	-10000	0	-0.64	25	25
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.018	0.079	-10000	0	-0.52	9	9
TRKA/NEDD4-2	-0.008	0.038	-10000	0	-10000	0	0
ELMO1	-0.31	0.41	-10000	0	-0.82	188	188
RhoG/GTP/ELMO1/DOCK1	-0.22	0.28	-10000	0	-0.56	189	189
NGF	0.006	0.071	-10000	0	-0.57	6	6
HRAS	0.012	0.021	-10000	0	-0.31	2	2
DOCK1	0.006	0.076	-10000	0	-0.82	4	4
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.21	0.23	-10000	0	-0.47	205	205
mol:GDP	-0.016	0.09	-10000	0	-0.42	3	3
NGF (dimer)	0.006	0.07	-10000	0	-0.57	6	6
RhoG/GDP	-0.25	0.31	-10000	0	-0.64	188	188
RIT1/GDP	-0.004	0.063	-10000	0	-0.3	1	1
TIAM1	-0.17	0.16	-10000	0	-0.82	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.022	0.11	-10000	0	-0.61	15	15
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.025	-10000	0	-0.55	1	1
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.05	0.2	-10000	0	-0.62	48	48
RAP1/GDP	-0.018	0.043	-10000	0	-10000	0	0
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.014	0.14	-10000	0	-0.6	21	21
ubiquitin-dependent protein catabolic process	-0.01	0.053	-10000	0	-0.55	3	3
Schwann cell development	-0.042	0.032	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.042	0.017	-10000	0	-10000	0	0
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.067	0.15	-10000	0	-0.47	52	52
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.037	-10000	0	-10000	0	0
STAT3	0.018	0.024	-10000	0	-10000	0	0
axon guidance	-0.065	0.15	-10000	0	-0.45	52	52
MAPK3	0.015	0.078	-10000	0	-0.5	8	8
MAPK1	0.015	0.078	-10000	0	-0.5	8	8
CDC42/GDP	-0.004	0.063	-10000	0	-0.28	2	2
NTF3	-0.05	0.21	-10000	0	-0.62	48	48
NTF4	-0.021	0.16	-10000	0	-0.64	25	25
NGF (dimer)/TRKA/FAIM	-0.01	0.053	-10000	0	-0.55	3	3
PI3K	-0.004	0.05	-10000	0	-0.63	3	3
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.13	0.11	-10000	0	-0.46	29	29
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.053	0.18	-10000	0	-0.59	40	40
RGS19	0.013	0	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.047	-10000	0	-0.42	1	1
Rac1/GDP	-0.004	0.063	-10000	0	-0.3	1	1
NGF (dimer)/TRKA/GRIT	-0.011	0.055	-10000	0	-0.56	3	3
neuron projection morphogenesis	0	0.095	-10000	0	-0.52	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.01	0.053	-10000	0	-0.55	3	3
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.063	0.19	-10000	0	-0.42	84	84
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.077	-10000	0	-0.35	18	18
RAS family/GTP/PI3K	0.03	0.032	-10000	0	-0.37	3	3
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.021	-10000	0	-0.46	1	1
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.057	-10000	0	-0.61	3	3
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.008	0.038	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.02	0.1	-10000	0	-0.56	15	15
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.008	0.043	-10000	0	-0.47	3	3
MATK	0	0.093	-10000	0	-0.53	12	12
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.015	0.042	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.036	0.099	-10000	0	-0.45	23	23
Rac1/GTP	-0.19	0.15	-10000	0	-0.36	192	192
FRS2 family/SHP2/CRK family	-0.001	0.021	-10000	0	-0.46	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.018	0.12	-10000	0	-0.79	11	11
HDAC1	0.002	0.009	-10000	0	-10000	0	0
AES	0.012	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.001	0.1	-10000	0	-0.82	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.007	0.066	-10000	0	-0.82	3	3
AP1	-0.14	0.26	-10000	0	-0.52	140	140
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.006	0.12	-10000	0	-0.82	11	11
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.054	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.017	0.11	-10000	0	-0.74	11	11
WIF1	-0.033	0.1	-10000	0	-0.31	58	58
NOTCH1	-0.018	0.12	-10000	0	-0.77	11	11
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.009	0.082	-10000	0	-0.31	33	33
DKK1	-0.042	0.12	-10000	0	-0.32	79	79
beta catenin/beta TrCP1	0.036	0.037	-10000	0	-10000	0	0
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	0	0.036	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.024	0.037	-10000	0	-0.35	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.21	0.37	-10000	0	-0.82	128	128
JUN	-0.18	0.35	-10000	0	-0.82	109	109
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.029	0.04	0.24	13	-10000	0	13
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.11	-10000	0	-0.55	19	19
HNF1A	0.012	0.002	-10000	0	-10000	0	0
CTBP1	0.012	0.002	-10000	0	-10000	0	0
MYC	-0.015	0.25	-10000	0	-1.5	13	13
NKD1	-0.013	0.14	-10000	0	-0.73	17	17
FZD1	0.013	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.023	0.12	-10000	0	-0.62	18	18
apoptosis	-0.14	0.26	-10000	0	-0.52	140	140
Delta 1/NOTCHprecursor	-0.018	0.12	-10000	0	-0.76	11	11
DLL1	0.011	0.041	-10000	0	-0.57	2	2
PPARD	0.024	0.017	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.001	0.06	-10000	0	-0.51	3	3
DVL1	0.003	0.01	-10000	0	-10000	0	0
CSNK2A1	0.014	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.037	0.078	-10000	0	-0.37	8	8
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.015	0.008	-10000	0	-10000	0	0
CCND1	0.019	0.043	-10000	0	-10000	0	0
WNT1	0.01	0.021	-10000	0	-0.31	2	2
Axin1/APC/beta catenin	0.043	0.052	-10000	0	-0.67	1	1
DKK2	-0.026	0.17	-10000	0	-0.66	28	28
NOTCH1 precursor/DVL1	-0.012	0.098	-10000	0	-0.65	11	11
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.024	0.12	-10000	0	-0.64	18	18
PPP2R5D	0.011	0.064	0.37	14	-10000	0	14
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.016	0.044	-10000	0	-10000	0	0
RBPJ	0.013	0.015	-10000	0	-0.31	1	1
CREBBP	0.017	0.004	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.012	0	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.001	0.013	-9999	-10000	0	0
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.015	0.064	-9999	-0.23	9	9
RAB3GAP2/RIMS1/UNC13B	-0.001	0.01	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.01	0.021	-9999	-0.31	2	2
mol:ACh	-0.007	0.041	-9999	-0.15	29	29
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.045	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.015	0.064	-9999	-0.23	9	9
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.018	0.094	-9999	-0.31	44	44
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.11	0.16	-9999	-0.4	61	61
SNAP25	-0.032	0.097	-9999	-0.38	29	29
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.16	0.23	-9999	-0.38	216	216
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.045	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	-0.062	0.16	-10000	0	-0.48	62	62
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.007	0.054	-10000	0	-0.21	31	31
GNB1/GNG2	-0.001	0.025	-10000	0	-0.56	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.066	0.17	-10000	0	-0.52	61	61
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.015	0.039	0.12	61	-10000	0	61
GNAL	-0.093	0.28	-10000	0	-0.82	61	61
GNG2	0.012	0.038	-10000	0	-0.82	1	1
CRH	-0.013	0.079	-10000	0	-0.31	31	31
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0.063	-10000	0	-0.46	9	9
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0.003	0.093	-9999	-0.82	6	6
CDKN1A	-0.013	0.088	-9999	-10000	0	0
PRL-3/alpha Tubulin	-0.016	0.054	-9999	-10000	0	0
mol:Ca2+	-0.014	0.11	-9999	-0.65	9	9
AGT	-0.019	0.13	-9999	-0.82	9	9
CCNA2	-0.062	0.2	-9999	-0.59	4	4
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.11	0.27	-9999	-0.63	102	102
CDK2/Cyclin E1	0.004	0.077	-9999	-10000	0	0
MAPK3	0.007	0.061	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.007	0.061	-9999	-10000	0	0
PTP4A1	-0.071	0.21	-9999	-0.48	102	102
PTP4A3	-0.012	0.088	-9999	-0.31	38	38
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.007	0.061	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1	-0.016	0.092	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.067	0.2	-9999	-0.45	102	102
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.012	0.04	-9999	-10000	0	0
RHOC	-0.016	0.092	-9999	-10000	0	0
RHOA	-0.016	0.092	-9999	-10000	0	0
cell motility	-0.014	0.098	-9999	-0.26	13	13
PRL-1/alpha Tubulin	-0.061	0.2	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.089	-9999	-0.66	6	6
ROCK1	-0.014	0.099	-9999	-0.27	13	13
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.071	0.21	-9999	-0.48	102	102
ATF5	0	0.065	-9999	-0.31	20	20

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.016	0.052	-9999	-0.55	4	4
ADCY5	-0.058	0.2	-9999	-0.56	65	65
ADCY6	0.016	0.052	-9999	-0.55	4	4
ADCY7	0.016	0.052	-9999	-0.55	4	4
ADCY1	0.009	0.078	-9999	-0.57	8	8
ADCY2	-0.041	0.18	-9999	-0.57	46	46
ADCY3	0.016	0.052	-9999	-0.55	4	4
ADCY8	-0.12	0.099	-9999	-0.7	4	4
PRKCE	0.007	0.059	-9999	-0.64	4	4
ADCY9	0.016	0.052	-9999	-0.55	4	4
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.056	0.1	-9999	-0.37	31	31

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.027	0.16	-9999	-0.44	64	64
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.05	0.12	-9999	-0.75	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.01	0.037	-9999	-0.65	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.024	0.061	-9999	-0.3	2	2
CaM/Ca2+	-0.056	0.14	-9999	-0.4	64	64
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.02	0.16	-9999	-0.41	64	64
AKT1	-0.003	0.15	-9999	-0.56	4	4
MAP2K1	-0.006	0.15	-9999	-0.52	5	5
MAP3K11	-0.017	0.16	-9999	-0.41	64	64
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.067	-9999	-0.64	1	1
Rap1/GTP	-0.041	0.1	-9999	-0.6	1	1
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.063	0.16	-9999	-0.46	63	63
CEBPB	0.016	0.18	-9999	-0.82	5	5
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.059	0.15	-9999	-1.1	2	2
STAT1	-0.02	0.16	-9999	-0.41	64	64
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.11	0.28	-9999	-0.72	78	78
PIK3CA	0.008	0.066	-9999	-0.82	3	3
STAT1 (dimer)/PIAS1	-0.011	0.15	-9999	-0.48	5	5
CEBPB/PTGES2/Cbp/p300	-0.035	0.083	-9999	-0.44	5	5
mol:Ca2+	-0.06	0.15	-9999	-0.43	64	64
MAPK3	0.009	0.14	-9999	-0.53	5	5
STAT1 (dimer)	-0.031	0.081	-9999	-0.42	2	2
MAPK1	0.009	0.14	-9999	-0.53	5	5
JAK2	0.008	0.043	-9999	-0.88	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.009	0.014	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.015	0.18	-9999	-0.66	24	24
SMAD7	0.041	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.05	0.12	-9999	-0.76	1	1
PI3K	-0.057	0.14	-9999	-0.52	8	8
IFNG	-0.11	0.28	-9999	-0.72	78	78
apoptosis	0.012	0.13	-9999	-0.45	24	24
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.004	0.068	-9999	-0.31	22	22
CAMK2B	0.005	0.085	-9999	-0.82	5	5
FRAP1	-0.001	0.14	-9999	-0.52	4	4
PRKCD	-0.002	0.15	-9999	-0.63	3	3
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.024	0.061	-9999	-0.3	2	2
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
IRF1	0.029	0.12	-9999	-0.53	1	1
STAT1 (dimer)/PIASy	-0.055	0.13	-9999	-0.48	5	5
SOCS1	0.001	0.075	-9999	-1.5	1	1
mol:GDP	-0.048	0.12	-9999	-0.71	1	1
CASP1	0.039	0.062	-9999	-0.35	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.041	0.058	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.055	0.14	-9999	-0.5	8	8
RAP1/GDP	-0.042	0.1	-9999	-0.61	1	1
CBL	-0.018	0.16	-9999	-0.41	64	64
MAP3K1	-0.017	0.16	-9999	-0.41	64	64
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.024	0.061	-9999	-0.3	2	2
PTPN11	-0.027	0.16	-9999	-0.43	64	64
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.014	0.12	-9999	-0.44	30	30
CCNA2	0.007	0.044	-9999	-0.31	9	9
PIK3CA	0.009	0.066	-9999	-0.82	3	3
JAK3	-0.067	0.14	-9999	-0.31	120	120
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.017	0.15	-9999	-0.56	19	19
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.043	0.25	-9999	-0.98	30	30
IL2RB	-0.014	0.13	-9999	-0.51	26	26
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.046	0.19	-9999	-0.55	52	52
G1/S transition of mitotic cell cycle	0.039	0.055	-9999	-0.59	3	3
PTPN11	0.012	0.038	-9999	-0.82	1	1
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.009	0.11	-9999	-0.44	25	25
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.005	0.006	-9999	-10000	0	0
CDK6	0.008	0.066	-9999	-0.82	3	3
CCND3	0.028	0.13	-9999	-0.64	7	7

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.34	-9999	-0.82	102	102
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.026	-9999	-0.31	3	3
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.023	-9999	-10000	0	0
HIF1A	0.022	0.024	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.004	0.041	-9999	-0.51	3	3
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.13	0.16	-9999	-0.31	206	206
ARNT/IPAS	-0.13	0.26	-9999	-0.63	102	102
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.023	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.023	-9999	-10000	0	0
PHD1-3/OS9	-0.018	0.089	-9999	-0.54	12	12
HIF1A/RACK1/Elongin B/Elongin C	-0.003	0.017	-9999	-10000	0	0
VHL	0.008	0.066	-9999	-0.82	3	3
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.023	-9999	-10000	0	0
EGLN3	-0.017	0.14	-9999	-0.51	28	28
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.01	0.054	-9999	-0.82	2	2
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.051	-9999	-0.6	3	3
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.073	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.004	0.11	0.57	14	-10000	0	14
PI3K Class IB/PDE3B	-0.004	0.11	-10000	0	-0.57	14	14
PDE3B	-0.004	0.11	-10000	0	-0.57	14	14

×

Ceramide 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
SPHK2	0.024	0	-10000	0	-10000	0	0
MAP4K4	-0.004	0.14	-10000	0	-0.7	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
PKC zeta/ceramide	-0.018	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.68	35	35
BAX	-0.005	0.019	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.023	0.008	-10000	0	-10000	0	0
BAD	-0.017	0.04	-10000	0	-10000	0	0
SMPD1	-0.007	0.097	-10000	0	-0.26	58	58
RB1	-0.018	0.046	-10000	0	-0.5	1	1
FADD/Caspase 8	0.008	0.14	-10000	0	-0.66	11	11
MAP2K4	-0.009	0.038	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.011	0.05	-10000	0	-0.52	2	2
EGF	-0.11	0.29	-10000	0	-0.78	74	74
mol:ceramide	-0.028	0.043	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.023	0.03	-10000	0	-0.63	1	1
ASAH1	0.012	0.038	-10000	0	-0.82	1	1
negative regulation of cell cycle	-0.019	0.045	-10000	0	-0.49	1	1
cell proliferation	-0.1	0.16	-10000	0	-0.39	113	113
BID	-0.018	0.093	-10000	0	-0.4	11	11
MAP3K1	-0.017	0.04	-10000	0	-10000	0	0
EIF2A	0	0.037	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.002	0.047	-10000	0	-0.48	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.002	0.047	-10000	0	-0.48	2	2
Cathepsin D/ceramide	-0.018	0.041	-10000	0	-0.16	1	1
FADD	-0.004	0.14	-10000	0	-0.7	11	11
KSR1	-0.019	0.053	-10000	0	-0.55	2	2
MAPK8	-0.009	0.056	-10000	0	-0.31	9	9
PRKRA	-0.017	0.04	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.18	0.35	-10000	0	-0.8	118	118
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.042	-10000	0	-10000	0	0
CTSD	0.013	0.015	-10000	0	-0.31	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.029	-10000	0	-0.63	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.087	0.19	-10000	0	-0.42	113	113
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.023	0.03	-10000	0	-0.63	1	1
RelA/NF kappa B1	-0.001	0.029	-10000	0	-0.63	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.15	-10000	0	-0.75	11	11
TNFR1A/BAG4/TNF-alpha	-0.069	0.18	-10000	0	-0.55	59	59
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.002	0.048	-10000	0	-0.49	2	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	0.004	0.052	0.18	26	-10000	0	26
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
TNFR1A/BAG4	-0.001	0.029	-10000	0	-0.63	1	1
EIF2AK2	-0.009	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.068	0.18	-10000	0	-0.55	58	58
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.014	0.08	-10000	0	-0.33	11	11
MAP2K2	-0.002	0.048	-10000	0	-0.49	2	2
SMPD3	-0.012	0.12	-10000	0	-0.3	63	63
TNF	-0.092	0.27	-10000	0	-0.82	58	58
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.023	0.11	0.28	68	-10000	0	68
NF kappa B1/RelA/I kappa B alpha	-0.001	0.021	-10000	0	-0.46	1	1
AIFM1	0.003	0.052	0.18	26	-10000	0	26
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

Signaling events mediated by HDAC Class III

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
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.021	0.03	0.63	1	-10000	0	1
CDKN1A	-0.007	0.039	-10000	0	-10000	0	0
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
FOXO3	0	0.007	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.024	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	0.006	0.03	-10000	0	-0.31	4	4
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.02	-10000	0	-10000	0	0
PPARGC1A	-0.35	0.42	-10000	0	-0.82	211	211
FHL2	-0.054	0.23	-10000	0	-0.82	39	39
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.031	-10000	0	-0.63	1	1
HIST2H4A	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/FOXO3a	0.001	0.027	-10000	0	-0.56	1	1
SIRT1	0.001	0.04	-10000	0	-0.82	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.028	-10000	0	-0.55	1	1
SIRT1/Histone H1b	-0.005	0.051	-10000	0	-0.33	10	10
apoptosis	-0.001	0.029	0.55	1	-10000	0	1
SIRT1/PGC1A	-0.24	0.28	-10000	0	-0.56	211	211
p53/SIRT1	0.005	0.045	-10000	0	-0.63	1	1
SIRT1/FOXO4	0.001	0.028	-10000	0	-0.53	1	1
FOXO1/FHL2/SIRT1	-0.04	0.14	-10000	0	-0.51	40	40
HIST1H1E	0.015	0.054	-10000	0	-0.37	9	9
SIRT1/p300	0.001	0.031	-10000	0	-0.63	1	1
muscle cell differentiation	0	0.031	0.55	1	-10000	0	1
TP53	0.003	0.013	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.029	-10000	0	-0.55	1	1
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.036	-10000	0	-0.63	1	1
ACSS2	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/PCAF/MYOD	0	0.031	-10000	0	-0.56	1	1

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.011	0.12	-10000	0	-0.88	2	2
UGCG	-0.04	0.17	-10000	0	-0.82	21	21
AKT1/mTOR/p70S6K/Hsp90/TERT	0.02	0.13	-10000	0	-0.41	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.019	0.18	-10000	0	-0.8	21	21
mol:DAG	0	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.06	0.14	-10000	0	-0.46	35	35
FRAP1	0.001	0.2	-10000	0	-0.54	35	35
FOXO3	0.019	0.17	-10000	0	-0.6	18	18
AKT1	0.01	0.18	-10000	0	-0.61	22	22
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	-0.006	0.023	-10000	0	-10000	0	0
SGMS1	-0.006	0.023	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.047	-10000	0	-0.56	3	3
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.001	0.16	-10000	0	-0.51	26	26
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.02	0.053	-10000	0	-0.64	3	3
RPS6KB1	0.016	0.041	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.012	5	5
JAK3	-0.066	0.14	-10000	0	-0.31	120	120
PIK3R1	0.015	0.005	-10000	0	-10000	0	0
JAK1	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MYC	0.007	0.22	-10000	0	-0.94	18	18
MYB	-0.016	0.2	-10000	0	-1.3	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.007	0.16	-10000	0	-0.55	25	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.038	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.008	0.16	-10000	0	-0.53	25	25
Rac1/GDP	0.024	0.043	-10000	0	-0.51	3	3
T cell proliferation	0.017	0.15	-10000	0	-0.5	22	22
SHC1	0.013	0.004	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.011	-10000	0	-0.051	16	16
PRKCZ	0.016	0.15	-10000	0	-0.53	22	22
NF kappa B1 p50/RelA	-0.058	0.14	-10000	0	-0.52	20	20
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.001	0.13	-10000	0	-0.6	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.048	0.2	-10000	0	-0.58	49	49
IL2RB	-0.013	0.13	-10000	0	-0.51	26	26
TERT	0	0.033	-10000	0	-0.31	5	5
E2F1	-0.005	0.076	-10000	0	-0.45	10	10
SOS1	0.013	0.004	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.024	16	-10000	0	16
PTPN11	0.011	0.039	-10000	0	-0.83	1	1
IL2RG	-0.045	0.19	-10000	0	-0.55	52	52
actin cytoskeleton organization	0.017	0.15	-10000	0	-0.5	22	22
GRB2	0.013	0.004	-10000	0	-10000	0	0
IL2	0.007	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.066	-10000	0	-0.83	3	3
Rac1/GTP	0.031	0.043	-10000	0	-0.49	3	3
LCK	-0.008	0.11	-10000	0	-0.43	25	25
BCL2	-0.025	0.28	-10000	0	-0.84	45	45

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.032	0.044	-9999	-0.93	1	1
VEGFR1 homodimer/NRP1	-0.002	0.043	-9999	-0.94	1	1
mol:DAG	-0.012	0.16	-9999	-0.49	49	49
VEGFR1 homodimer/NRP1/VEGFR 121	-0.005	0.068	-9999	-0.78	3	3
CaM/Ca2+	-0.004	0.15	-9999	-0.46	49	49
HIF1A	0.021	0.018	-9999	-0.38	1	1
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.009	0.17	-9999	-1.1	2	2
PLCG1	-0.012	0.16	-9999	-0.5	49	49
NOS3	0.017	0.15	-9999	-0.91	1	1
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.018	0.15	-9999	-0.85	1	1
FLT1	0.031	0.049	-9999	-1	1	1
PGF	-0.071	0.25	-9999	-0.81	49	49
VEGFR1 homodimer/NRP2/VEGFR121	-0.015	0.075	-9999	-0.77	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
eNOS/Hsp90	0.025	0.14	-9999	-0.81	1	1
endothelial cell proliferation	-0.028	0.19	-9999	-0.52	50	50
mol:Ca2+	-0.012	0.16	-9999	-0.49	49	49
MAPK3	-0.016	0.18	-9999	-1	2	2
MAPK1	-0.016	0.18	-9999	-1	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.071	0.25	-9999	-0.81	49	49
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.009	0.14	-9999	-0.82	13	13
VEGFA homodimer	0.008	0.066	-9999	-0.82	3	3
VEGFR1 homodimer/VEGFA homodimer	0.029	0.075	-9999	-0.82	3	3
platelet activating factor biosynthetic process	-0.007	0.17	-9999	-0.96	2	2
PI3K	-0.05	0.15	-9999	-0.47	51	51
PRKCA	-0.025	0.19	-9999	-0.47	69	69
PRKCB	-0.022	0.17	-9999	-0.47	53	53
VEGFR1 homodimer/PLGF homodimer	-0.025	0.18	-9999	-0.55	49	49
VEGFA	0.008	0.066	-9999	-0.82	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.012	0.16	-9999	-0.49	49	49
RASA1	0.041	0.041	-9999	-0.86	1	1
NRP2	-0.012	0.088	-9999	-0.31	38	38
VEGFR1 homodimer	0.031	0.048	-9999	-1	1	1
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.012	0.16	-9999	-0.8	4	4
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:PI-3-4-5-P3	-0.05	0.15	-9999	-0.47	51	51
mol:L-citrulline	0.018	0.15	-9999	-0.85	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.005	0.064	-9999	-0.73	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.005	0.068	-9999	-0.77	3	3
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.047	0.14	-9999	-1.2	1	1
PDPK1	0	0.16	-9999	-1.2	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.006	0.084	-9999	-0.9	3	3
mol:NADP	0.018	0.15	-9999	-0.85	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.004	0.062	-9999	-0.71	3	3
VEGFR1 homodimer/NRP2	0.018	0.066	-9999	-0.93	1	1

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.052	0.14	-9999	-0.44	57	57
TC10/GTP	-0.003	0.033	-9999	-0.42	3	3
Insulin Receptor/Insulin/IRS1/Shp2	-0.06	0.17	-9999	-0.52	55	55
HRAS	0.012	0.021	-9999	-0.31	2	2
APS homodimer	0.013	0.015	-9999	-0.31	1	1
GRB14	-0.009	0.14	-9999	-0.82	13	13
FOXO3	-0.025	0.11	-9999	-0.72	11	11
AKT1	-0.01	0.16	-9999	-0.89	2	2
INSR	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.008	0.066	-9999	-0.82	3	3
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.038	0	-9999	-10000	0	0
CAV1	-0.043	0.18	-9999	-0.48	68	68
CBL/APS/CAP/Crk-II/C3G	-0.003	0.037	-9999	-0.46	3	3
Insulin Receptor/Insulin/IRS1/NCK2	-0.059	0.16	-9999	-0.51	55	55
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.054	0.15	-9999	-0.46	57	57
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.005	0.1	-9999	-10000	0	0
RPS6KB1	0.001	0.15	-9999	-0.76	2	2
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.053	0.13	-9999	-0.78	2	2
HRAS/GTP	-0.048	0.12	-9999	-0.5	3	3
Insulin Receptor	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.054	0.15	-9999	-0.48	55	55
PRKCI	-0.014	0.034	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.062	0.16	-9999	-1	2	2
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.055	0.15	-9999	-0.46	57	57
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
AKT2	-0.01	0.16	-9999	-0.89	2	2
PRKCZ	-0.014	0.034	-9999	-10000	0	0
SH2B2	0.013	0.015	-9999	-0.31	1	1
SHC/SHIP	-0.027	0.16	-9999	-0.45	55	55
F2RL2	-0.08	0.16	-9999	-0.32	133	133
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.003	0.039	-9999	-0.5	3	3
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.037	0.16	-9999	-0.49	55	55
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.028	0.16	-9999	-1	11	11
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.082	0.27	-9999	-0.82	55	55
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.037	0.16	-9999	-0.48	55	55
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.001	0.15	-9999	-0.64	4	4
PTPRA	0.015	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0.054	-9999	-0.82	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.006	0.12	-9999	-0.33	55	55
Insulin Receptor/Insulin/IRS1	-0.06	0.17	-9999	-0.52	55	55
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.036	0.064	-9999	-0.47	3	3

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
ITGA4	0.004	0.069	-9999	-0.41	11	11
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.62	15	15
alpha4/beta1 Integrin	-0.006	0.049	-9999	-0.63	2	2

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.004	0.12	-10000	0	-0.82	10	10
ANTXR2	0.008	0.066	-10000	0	-0.82	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.017	-10000	0	-0.1	13	13
monocyte activation	-0.048	0.17	-10000	0	-0.48	61	61
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.014	-10000	0	-10000	0	0
MAP2K7	-0.002	0.014	-10000	0	-10000	0	0
MAP2K6	-0.013	0.073	-10000	0	-0.5	10	10
CYAA	0.003	0.081	-10000	0	-0.48	13	13
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.025	0.14	-10000	0	-0.47	40	40
Channel	-0.014	0.083	-10000	0	-0.51	13	13
NLRP1	-0.004	0.035	-10000	0	-0.49	2	2
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.017	0.1	13	-10000	0	13
MAPK3	-0.002	0.014	-10000	0	-10000	0	0
MAPK1	-0.002	0.014	-10000	0	-10000	0	0
PGR	-0.023	0.087	-10000	0	-0.47	15	15
PA/Cellular Receptors	-0.015	0.09	-10000	0	-0.56	13	13
apoptosis	-0.003	0.017	-10000	0	-0.1	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.003	0.081	-10000	0	-0.48	13	13
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.092	0.27	-10000	0	-0.82	58	58
VCAM1	-0.049	0.17	-10000	0	-0.49	61	61
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.024	0.11	10	-10000	0	10
IL18	-0.011	0.087	-10000	0	-0.42	14	14
negative regulation of macrophage activation	-0.003	0.017	-10000	0	-0.1	13	13
LEF	-0.003	0.017	-10000	0	-0.1	13	13
CASP1	-0.004	0.02	-10000	0	-0.22	2	2
mol:cAMP	-0.003	0.02	-10000	0	-10000	0	0
necrosis	-0.003	0.017	-10000	0	-0.1	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.013	0.079	-10000	0	-0.49	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.012	0.038	-9999	-0.82	1	1
Caspase 8 (4 units)	-0.02	0.06	-9999	-10000	0	0
NEF	-0.011	0.053	-9999	-10000	0	0
NFKBIA	0.009	0.03	-9999	-10000	0	0
BIRC3	-0.005	0.2	-9999	-0.81	26	26
CYCS	-0.005	0.1	-9999	-0.4	5	5
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.035	0.18	-9999	-0.71	27	27
MAP2K7	0.025	0.078	-9999	-10000	0	0
protein ubiquitination	0.039	0.088	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	-0.013	0.1	-9999	-0.42	5	5
NF-kappa-B/RelA/I kappa B alpha	-0.022	0.081	-9999	-0.35	26	26
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.022	0.081	-9999	-0.35	26	26
MAPK8	0.024	0.096	-9999	-0.42	9	9
APAF1	0.012	0.038	-9999	-0.82	1	1
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.094	-9999	-0.31	26	26
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.1	-9999	-0.36	11	11
CHUK	0.039	0.093	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.021	-9999	-0.46	1	1
TCRz/NEF	-0.057	0.17	-9999	-0.52	48	48
TNF	-0.092	0.27	-9999	-0.82	58	58
FASLG	-0.065	0.28	-9999	-0.84	48	48
NFKB1	0.007	0.048	-9999	-0.82	1	1
TNFR1A/BAG4/TNF-alpha	-0.069	0.18	-9999	-0.55	59	59
CASP6	-0.003	0.045	-9999	-10000	0	0
CASP7	0.03	0.17	-9999	-0.62	25	25
RELA	0.009	0.03	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.03	0.17	-9999	-0.62	25	25
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.029	-9999	-0.63	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.099	-9999	-0.37	2	2
APAF-1/Caspase 9	-0.046	0.12	-9999	-0.52	25	25
BCL2	-0.001	0.15	-9999	-0.41	41	41

×

Regulation of Telomerase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.023	0.092	-9999	-10000	0	0
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.29	0.45	-9999	-0.92	151	151
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	-0.001	0.07	-9999	-0.29	23	23
ER alpha/Oestrogen	-0.044	0.14	-9999	-0.4	54	54
NFX1/SIN3/HDAC complex	0.047	0.026	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.007	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.035	0.068	-9999	-10000	0	0
SAP18	0.014	0	-9999	-10000	0	0
MRN complex	-0.003	0.043	-9999	-0.55	3	3
WT1	-0.025	0.1	-9999	-0.31	53	53
WRN	0.012	0.038	-9999	-0.82	1	1
SP1	0.015	0.003	-9999	-10000	0	0
SP3	0.014	0.002	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.029	0.053	-9999	-10000	0	0
Mad/Max	0.006	0.01	-9999	-10000	0	0
TERT	-0.024	0.093	-9999	-10000	0	0
CCND1	-0.015	0.092	-9999	-10000	0	0
MAX	0.014	0.002	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
RBBP4	0.008	0.066	-9999	-0.82	3	3
TERF2	0	0.005	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
Telomerase/911	0.036	0.02	-9999	-10000	0	0
CDKN1B	-0.04	0.19	-9999	-0.52	63	63
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.001	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.82	109	109
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.003	0.006	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	128	128
IFN-gamma/IRF1	-0.087	0.21	-9999	-0.61	64	64
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.013	0.015	-9999	-0.31	1	1
Telomerase	0.014	0.072	-9999	-0.48	5	5
IRF1	0.018	0.015	-9999	-10000	0	0
ESR1	-0.047	0.19	-9999	-0.53	54	54
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.025	-9999	-0.56	1	1
ubiquitin-dependent protein catabolic process	0.052	0.027	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.053	0.027	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC2	0.015	0.003	-9999	-10000	0	0
ATM	-0.001	0.026	-9999	-0.56	1	1
SMAD3	0.02	0.029	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.014	0.002	-9999	-10000	0	0
MRE11A	0.008	0.066	-9999	-0.82	3	3
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.031	0.065	-9999	-10000	0	0
NR2F2	0.012	0.002	-9999	-10000	0	0
MAPK3	0.017	0.006	-9999	-10000	0	0
MAPK1	0.017	0.006	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.008	0.042	-9999	-0.31	8	8
NFKB1	0.012	0.038	-9999	-0.82	1	1
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.026	-9999	-0.56	1	1
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.007	0.076	-9999	-0.82	4	4
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.097	0.22	-9999	-0.63	72	72
MYC	-0.009	0.14	-9999	-0.82	13	13
IL2	0.006	0.007	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.008	0.042	-9999	-0.31	8	8
TRF2/BLM	0	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.018	0.078	-9999	-10000	0	0
SP1/HDAC2	0.022	0.007	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.029	0.053	-9999	-10000	0	0
Smad3/Myc	0.009	0.097	-9999	-0.56	13	13
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.1	0.28	-9999	-0.71	78	78
Telomerase/PinX1	-0.029	0.053	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.021	0.037	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.029	0.053	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.003	0.036	-9999	-0.46	3	3
TRF2/WRN	-0.001	0.027	-9999	-0.59	1	1
Telomerase/hnRNP C1/C2	-0.029	0.053	-9999	-10000	0	0
E2F1	-0.087	0.15	-9999	-0.31	150	150
ZNFX1	0.014	0	-9999	-10000	0	0
PIF1	0.002	0.09	-9999	-0.6	9	9
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.042	0.12	0.33	1	-0.36	57	58
FRAP1	0.008	0.027	-10000	0	-10000	0	0
AKT1	-0.035	0.1	0.25	1	-0.66	3	4
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.027	0.077	-10000	0	-0.51	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.007	0.022	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.022	0.065	-10000	0	-0.46	3	3
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.033	0.14	-10000	0	-0.42	55	55
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.009	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0.06	-10000	0	-0.35	3	3
MAP3K5	0.011	0.021	-10000	0	-0.45	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.021	-10000	0	-0.45	1	1
mol:LY294002	0	0.001	0.001	1	-0.002	54	55
EIF4B	0.017	0.054	-10000	0	-0.34	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.013	0.039	-10000	0	-0.32	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.024	0.14	-10000	0	-0.39	57	57
mTOR/RHEB/GTP/Raptor/GBL	0.021	0.04	0.18	1	-0.28	2	3
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.022	0.064	-10000	0	-0.45	3	3
mol:Amino Acids	0	0.001	0.001	1	-0.002	54	55
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.039	0.12	0.26	1	-0.34	57	58
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.034	-10000	0	-0.62	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.029	0.083	-10000	0	-0.56	3	3
tumor necrosis factor receptor activity	0	0.001	0.002	54	-0.001	1	55
RPS6	0.013	0	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	-0.044	0.15	-10000	0	-0.46	55	55
INS	0	0	-10000	0	-10000	0	0
PTEN	0.011	0.038	-10000	0	-0.82	1	1
PDK2	-0.038	0.11	0.26	1	-0.32	57	58
EIF4EBP1	0.012	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PPP2R5D	0.015	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.018	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.004	3	4
EEF2	0.018	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.019	0.008	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.046	0.06	-10000	0	-0.38	8	8
NFATC2	-0.019	0.095	-10000	0	-0.29	26	26
NFATC3	0.018	0.012	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.091	-10000	0	-0.32	24	24
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.002	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.025	0.097	-10000	0	-0.59	9	9
BCL2/BAX	-0.046	0.16	-10000	0	-0.63	35	35
CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.006	0.01	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.016	0.086	-10000	0	-0.57	4	4
Calcineurin A alpha-beta B1/BCL2	-0.047	0.22	-10000	0	-0.82	35	35
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.016	0.085	0.56	4	-10000	0	4
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.013	0	-10000	0	-10000	0	0
XPO1	0.013	0.001	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	310	310
MAP3K8	-0.004	0.11	-10000	0	-0.83	8	8
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.12	0.16	-10000	0	-0.49	22	22
CABIN1	0.012	0.091	-10000	0	-0.32	24	24
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
MAP3K1	0.013	0	-10000	0	-10000	0	0
CAMK4	-0.005	0.11	-10000	0	-0.54	16	16
mol:Ca2+	-0.005	0.009	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.006	0.11	-10000	0	-0.82	9	9
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.006	0.05	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.006	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.014	0.051	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.047	-10000	0	-10000	0	0
PRKCB	-0.027	0.13	-10000	0	-0.36	52	52
PRKCE	0.006	0.076	-10000	0	-0.82	4	4
JNK2/NFAT4	0.022	0.014	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.013	0.001	-10000	0	-10000	0	0
PRKCZ	0.01	0.006	-10000	0	-10000	0	0
PRKCA	-0.025	0.18	-10000	0	-0.82	22	22
PRKCG	0.005	0.022	-10000	0	-0.31	2	2
PRKCQ	0.005	0.085	-10000	0	-0.82	5	5
FKBP38/BCL2	-0.046	0.16	-10000	0	-0.63	35	35
EP300	0.01	0.007	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.032	0.086	-10000	0	-0.38	17	17
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.01	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.012	0.071	-10000	0	-0.56	7	7
NFATc/ERK1	0.052	0.057	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.025	0.096	-10000	0	-0.58	9	9
NR4A1	-0.19	0.36	-10000	0	-0.73	143	143
GSK3B	0.01	0.006	-10000	0	-10000	0	0
positive T cell selection	0.018	0.012	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.036	0.062	-10000	0	-0.41	4	4
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
AKAP5	0.013	0	-10000	0	-10000	0	0
MEF2D	0.01	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.041	0.062	-10000	0	-10000	0	0
CREBBP	0.01	0.007	-10000	0	-10000	0	0
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

Stabilization and expansion of the E-cadherin adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.033	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
ENAH	0.071	0.009	-9999	-10000	0	0
EGFR	0.006	0.076	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
MYO6	0.041	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0	0	-9999	-10000	0	0
AQP5	-0.039	0.13	-9999	-0.59	25	25
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.04	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.074	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.074	0.2	-9999	-0.59	60	60
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GDP	0	0.005	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.049	0.032	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.041	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.009	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.065	0.15	-9999	-0.43	72	72
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.047	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.18	0.35	-9999	-0.8	118	118
DIAPH1	0	0.002	-9999	-10000	0	0
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0.005	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.048	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.041	0.057	-9999	-0.43	7	7
Ephrin A1/EPHA2	-0.001	0.008	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.038	0.074	-9999	-10000	0	0
HGF/MET	-0.1	0.16	-9999	-0.48	73	73
HGF	-0.11	0.3	-9999	-0.82	73	73
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.033	0	-9999	-10000	0	0
actin cable formation	0.086	0.02	-9999	-10000	0	0
KIAA1543	0.047	0.021	-9999	-0.42	1	1
KIFC3	0.041	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.04	0.007	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.041	0	-9999	-10000	0	0
PIP5K1C	0.041	0	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.064	0.02	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-9999	-0.43	112	112
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	179	179
PLEKHA7	0.04	0.022	-9999	-0.45	1	1
mol:GTP	-0.001	0.01	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.067	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.033	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.047	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.033	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.018	0.093	-10000	0	-0.46	12	12
ACTA1	0.01	0.12	-10000	0	-0.64	10	10
NUMA1	0.018	0.093	-10000	0	-0.46	12	12
SPTAN1	0.015	0.12	-10000	0	-0.64	10	10
LIMK1	0.015	0.12	-10000	0	-0.64	10	10
BIRC3	-0.037	0.19	-10000	0	-0.68	35	35
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
CASP10	-0.001	0.12	-10000	0	-0.67	12	12
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	0.018	0.093	-10000	0	-0.46	12	12
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.015	0.11	-10000	0	-0.62	10	10
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	0.015	0.12	-10000	0	-0.64	10	10
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.058	0.22	-10000	0	-0.65	60	60
BID	-0.011	0.068	-10000	0	-0.31	12	12
MAP3K1	0.014	0.042	-10000	0	-0.23	3	3
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.029	-10000	0	-0.63	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.012	0.12	-10000	0	-0.61	11	11
CASP9	0.013	0	-10000	0	-10000	0	0
DNA repair	-0.016	0.052	0.17	1	-0.23	22	23
neuron apoptosis	0.023	0.015	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.021	0.11	-10000	0	-0.61	10	10
APAF1	0.012	0.038	-10000	0	-0.82	1	1
CASP6	0.022	0.064	-10000	0	-0.43	4	4
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.022	0.11	-10000	0	-0.61	10	10
CASP7	0.009	0.08	0.34	25	-10000	0	25
KRT18	0.017	0.018	-10000	0	-10000	0	0
apoptosis	0.026	0.11	-10000	0	-0.56	12	12
DFFA	0.015	0.12	-10000	0	-0.64	10	10
DFFB	0.015	0.12	-10000	0	-0.64	10	10
PARP1	0.016	0.052	0.23	22	-0.18	1	23
actin filament polymerization	-0.023	0.11	0.58	10	-10000	0	10
TNF	-0.092	0.27	-10000	0	-0.82	58	58
CYCS	0.005	0.045	-10000	0	-0.22	12	12
SATB1	0.029	0.061	-10000	0	-0.4	4	4
SLK	0.012	0.13	-10000	0	-0.67	12	12
p15 BID/BAX	-0.003	0.061	-10000	0	-0.35	4	4
CASP2	0.005	0.12	-10000	0	-0.46	11	11
JNK cascade	-0.014	0.042	0.23	3	-10000	0	3
CASP3	0.007	0.12	-10000	0	-0.62	12	12
LMNB2	0.02	0.077	-10000	0	-0.32	4	4
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.029	0.11	-10000	0	-0.5	25	25
negative regulation of DNA binding	-0.057	0.22	-10000	0	-0.64	60	60
stress fiber formation	0.012	0.13	-10000	0	-0.65	12	12
GZMB	-0.013	0.14	-10000	0	-0.71	14	14
CASP1	0.016	0.032	-10000	0	-0.45	2	2
LMNB1	0.02	0.077	-10000	0	-0.32	4	4
APP	0.023	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	0.022	0.1	-10000	0	-0.51	10	10
LMNA	0.02	0.077	-10000	0	-0.32	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.003	0.12	-10000	0	-0.49	11	11
LRDD	0.013	0	-10000	0	-10000	0	0
SREBF1	0.014	0.12	-10000	0	-0.64	10	10
APAF-1/Caspase 9	0.005	0.042	-10000	0	-0.4	1	1
nuclear fragmentation during apoptosis	0.019	0.091	-10000	0	-0.46	12	12
CFL2	0.022	0.11	-10000	0	-0.6	10	10
GAS2	0.01	0.13	-10000	0	-0.6	15	15
positive regulation of apoptosis	0.022	0.079	-10000	0	-0.33	3	3
PRF1	-0.002	0.11	-10000	0	-0.72	10	10

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.033	0.14	-10000	0	-0.63	25	25
ATM	0.012	0.038	-10000	0	-0.82	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.012	0.038	-10000	0	-0.82	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.03	-10000	0	-0.44	2	2
protein ubiquitination	-0.025	0.1	-10000	0	-0.46	26	26
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	-0.003	0.043	-10000	0	-0.55	3	3
MRE11A	0.008	0.066	-10000	0	-0.82	3	3
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.013	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0	0	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.033	0.14	-10000	0	-0.63	25	25
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	-0.001	0.067	-10000	0	-10000	0	0
DNA repair	0.054	0.099	-10000	0	-0.41	1	1
BRCA1/BARD1/ubiquitin	-0.033	0.14	-10000	0	-0.63	25	25
BARD1/DNA-PK	-0.026	0.11	-10000	0	-0.5	25	25
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.033	0.14	0.63	25	-10000	0	25
BRCA1/BARD1/CTIP/M/R/N Complex	0.021	0.09	-10000	0	-0.39	4	4
BRCA1/BACH1/BARD1/TopBP1	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/P53	-0.027	0.11	-10000	0	-0.5	26	26
BARD1/CSTF1/BRCA1	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.03	0.19	-10000	0	-0.82	25	25
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/UbcH7	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/RAD51/PCNA	-0.026	0.11	-10000	0	-0.5	25	25
BARD1/DNA-PK/P53	-0.024	0.1	-10000	0	-0.46	25	25
BRCA1/BARD1/Ubiquitin	-0.033	0.14	-10000	0	-0.63	25	25
BRCA1/BARD1/CTIP	-0.027	0.11	-10000	0	-0.5	26	26
FA complex	0.038	0.024	-10000	0	-10000	0	0
BARD1/EWS	-0.033	0.14	-10000	0	-0.63	25	25
RBBP8	0.023	0.03	-10000	0	-0.63	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.027	0.11	0.49	26	-10000	0	26
BRCA1/BARD1	-0.025	0.1	-10000	0	-0.46	26	26
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.033	0.14	-10000	0	-0.64	25	25
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.012	0.021	-10000	0	-0.31	2	2
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.033	0.14	-10000	0	-0.63	25	25
EWSR1	0.013	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.013	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-0.31	1	1
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.06	-10000	0	-0.34	6	6
KAT2B	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
AKT1	0.011	0.084	0.24	5	-0.41	14	19
RAR alpha/9cRA/Cyclin H	-0.023	0.092	-10000	0	-0.41	22	22
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.067	-10000	0	-0.39	6	6
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.014	0.11	-10000	0	-0.39	29	29
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-10000	0	-0.21	1	1
RXRs/RARs/NRIP1/9cRA	-0.019	0.16	-10000	0	-0.63	25	25
NCOA2	-0.063	0.24	-10000	0	-0.82	44	44
NCOA3	0.013	0	-10000	0	-10000	0	0
NCOA1	0.013	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-10000	0	-0.31	1	1
RARG	0.014	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.002	-10000	0	-10000	0	0
MAPK1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.11	-10000	0	-0.82	9	9
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.037	0.14	-10000	0	-0.66	22	22
RARA	0.007	0.091	-10000	0	-0.34	29	29
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0	0.14	-10000	0	-0.55	16	16
PRKCA	-0.022	0.18	-10000	0	-0.82	22	22
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.03	0.16	-10000	0	-0.65	25	25
RXRG	-0.12	0.11	-10000	0	-0.53	26	26
RXRA	0.013	0.092	-10000	0	-0.34	29	29
RXRB	0.005	0.099	-10000	0	-0.44	22	22
VDR/Vit D3/DNA	0	0.01	-10000	0	-0.21	1	1
RBP1	-0.002	0.1	-10000	0	-0.64	11	11
CRBP1/9-cic-RA	-0.011	0.079	-10000	0	-0.64	7	7
RARB	-0.007	0.14	-10000	0	-0.82	13	13
PRKCG	0.008	0.022	-10000	0	-0.31	2	2
MNAT1	0.013	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.026	0.16	-10000	0	-0.68	25	25
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.008	0.14	-10000	0	-0.55	25	25
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.087	-10000	0	-0.49	7	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.03	0.16	-10000	0	-0.65	25	25
positive regulation of DNA binding	-0.022	0.087	-10000	0	-0.38	22	22
NRIP1	-0.025	0.14	-10000	0	-0.63	19	19
RXRs/RARs	-0.038	0.16	-10000	0	-0.65	25	25
RXRs/RXRs/DNA/9cRA	-0.048	0.14	-10000	0	-0.69	22	22
PRKACA	0.013	0	-10000	0	-10000	0	0
CDK7	0.013	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.012	0.053	-10000	0	-0.53	2	2
CCNH	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.038	-9999	-0.82	1	1
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.058	-9999	-0.28	17	17
GNAO1	-0.015	0.15	-9999	-0.72	20	20
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.005	0.029	-9999	-0.47	1	1
AKT3	0.049	0.05	-9999	-0.56	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.013	0.038	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.036	0.067	-9999	-0.32	16	16
MAPK3	0.042	0.064	-9999	-10000	0	0
MAPK1	0.042	0.064	-9999	-10000	0	0
JAK2	0.046	0.066	-9999	-0.43	1	1
CXCR4	0.042	0.065	-9999	-10000	0	0
FLT1	0.015	0.038	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.042	0.064	-9999	-10000	0	0
S1P/S1P3/Gi	0.036	0.068	-9999	-0.32	16	16
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.01	0.052	-9999	-10000	0	0
VEGFA	0.011	0.066	-9999	-0.82	3	3
S1P/S1P2/Gi	0.03	0.069	-9999	-0.32	16	16
VEGFR1 homodimer/VEGFA homodimer	0.024	0.068	-9999	-0.8	3	3
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.066	0.17	-9999	-0.35	119	119
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.015	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.094	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.002	0.11	-9999	-0.82	9	9
Rac1/GTP	-0.01	0.052	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	0.006	0.049	-9999	-0.31	11	11
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.022	0.016	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.72	20	20
mol:Sphinganine-1-P	0.019	0.034	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.002	0.014	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.013	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.011	-9999	-10000	0	0
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
GNAI1	0.012	0.038	-9999	-0.82	1	1
S1P/S1P5/G12	-0.004	0.029	-9999	-0.49	1	1
S1P/S1P3/Gq	-0.049	0.15	-9999	-0.4	23	23
S1P/S1P4/Gi	0.031	0.068	-9999	-0.32	17	17
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.094	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.002	0.11	-9999	-0.82	9	9
ABCC1	0.013	0	-9999	-10000	0	0

×

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	0.024	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.039	0.016	-10000	0	-0.26	1	1
CDKN1A	0.033	0.032	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
FOXO3	0.039	0.016	-10000	0	-10000	0	0
AKT1	-0.001	0.015	-10000	0	-0.28	1	1
BAD	0.013	0	-10000	0	-10000	0	0
AKT3	0.016	0.03	-10000	0	-0.45	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.039	0.016	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.024	-10000	0	-0.43	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.012	0.038	-10000	0	-0.82	1	1
RAF1	0.013	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.023	0.42	1	-10000	0	1
TSC1	0.039	0.016	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
AKT1/RAF1	0.038	0.016	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.032	0.017	-10000	0	-0.28	1	1
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.039	0.016	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.053	0.2	-10000	0	-0.55	66	66
MAP3K5	0.012	0.038	-10000	0	-0.82	1	1
MAPKAP1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.035	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
AKT1S1	0.039	0.016	-10000	0	-10000	0	0
CASP9	0.039	0.016	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.045	0.015	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.003	0.036	-10000	0	-0.55	2	2
YWHAE	0.013	0	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
AKT2/p21CIP1	-0.005	0.03	-10000	0	-0.37	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.039	0.016	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.015	-10000	0	-10000	0	0
mTORC2	-0.001	0.023	-10000	0	-0.51	1	1
AKT2	0.016	0.03	-10000	0	-0.45	2	2
FOXO1-3a-4/14-3-3 family	0.024	0.041	-10000	0	-10000	0	0
PDPK1	0.01	0.054	-10000	0	-0.82	2	2
MDM2	0.039	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.016	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.051	0.015	-10000	0	-10000	0	0
TSC1/TSC2	0.046	0.016	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.011	-10000	0	-10000	0	0
glucose import	-0.06	0.21	-10000	0	-0.52	80	80
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.033	0.012	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.061	0.21	-10000	0	-0.53	80	80
GSK3A	0.039	0.016	-10000	0	-10000	0	0
FOXO1	0.039	0.016	-10000	0	-10000	0	0
GSK3B	0.039	0.016	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	310	310
G1/S transition of mitotic cell cycle	0.046	0.016	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.001	0.052	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
KPNA1	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.004	0.13	-10000	0	-0.56	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
BAD	0.017	0.046	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.68	35	35
BAX	0.017	0.047	-10000	0	-0.22	1	1
EnzymeConsortium:3.1.4.12	0.004	0.034	-10000	0	-0.12	11	11
IKBKB	0.012	0.12	-10000	0	-0.52	11	11
MAP2K2	0.027	0.057	-10000	0	-0.37	2	2
MAP2K1	0.027	0.057	-10000	0	-0.37	2	2
SMPD1	0.01	0.034	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.012	0.13	-10000	0	-0.54	11	11
MAP2K4	0.024	0.047	-10000	0	-10000	0	0
protein ubiquitination	0.014	0.13	-10000	0	-0.53	11	11
EnzymeConsortium:2.7.1.37	0.03	0.062	-10000	0	-0.37	2	2
response to UV	0	0.001	-10000	0	-0.003	2	2
RAF1	0.022	0.057	-10000	0	-0.4	2	2
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.048	-10000	0	-0.17	11	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.017	0.048	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.013	0	-10000	0	-10000	0	0
MAPK3	0.03	0.056	-10000	0	-0.36	2	2
MAPK1	0.03	0.056	-10000	0	-0.36	2	2
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.004	0.13	-10000	0	-0.56	11	11
KSR1	0.015	0.057	-10000	0	-0.43	2	2
MAPK8	0.023	0.078	-10000	0	-0.44	9	9
TRAF2	0.013	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.012	0.12	-10000	0	-0.52	11	11
TNF R/SODD	-0.001	0.029	-10000	0	-0.63	1	1
TNF	-0.092	0.27	-10000	0	-0.82	58	58
CYCS	0.027	0.057	0.16	29	-10000	0	29
IKBKG	0.012	0.12	-10000	0	-0.52	11	11
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.14	-10000	0	-0.45	25	25
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AIFM1	0.027	0.057	0.16	29	-10000	0	29
TNF/TNF R/SODD	-0.069	0.18	-10000	0	-0.55	59	59
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.019	0.033	-10000	0	-10000	0	0
NSMAF	0.004	0.13	-10000	0	-0.55	11	11
response to hydrogen peroxide	0	0.001	-10000	0	-0.003	2	2
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

TRAIL signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.067	-9999	-0.7	4	4
positive regulation of NF-kappaB transcription factor activity	-0.004	0.05	-9999	-0.63	3	3
MAP2K4	0.047	0.031	-9999	-0.3	3	3
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.008	0.066	-9999	-0.82	3	3
SMPD1	-0.002	0.023	-9999	-0.29	3	3
IKBKG	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.004	0.051	-9999	-0.63	3	3
TRAIL/TRAILR3	-0.06	0.1	-9999	-0.68	3	3
TRAIL/TRAILR1	-0.008	0.071	-9999	-0.63	6	6
TRAIL/TRAILR4	-0.004	0.051	-9999	-0.63	3	3
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.056	-9999	-0.5	6	6
IKK complex	-0.002	0.017	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.052	-9999	-0.63	3	3
MAP3K1	-0.003	0.028	-9999	-0.32	3	3
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.066	-9999	-0.82	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.035	0.041	-9999	-0.33	6	6
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.02	0.052	-9999	-0.63	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.006	0.052	-9999	-0.46	6	6
mol:ceramide	-0.002	0.023	-9999	-0.29	3	3
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.045	0.077	-9999	-0.47	9	9
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.077	0.15	-9999	-0.31	134	134
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.007	0.061	-9999	-0.55	6	6
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.005	0.046	-9999	-0.52	3	3
JNK cascade	-0.004	0.05	-9999	-0.63	3	3
TRAIL (trimer)	0.007	0.067	-9999	-0.7	4	4
TNFRSF10C	-0.077	0.15	-9999	-0.31	134	134
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.006	0.053	-9999	-0.47	6	6
TRAIL/TRAILR2/FADD	-0.004	0.044	-9999	-0.55	3	3
cell death	0.019	0.025	-9999	-0.29	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.037	0.029	-9999	-0.33	3	3
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.013	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.037	-9999	-0.46	3	3

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.077	-9999	-0.74	5	5
PDGFRB	0.012	0.038	-9999	-0.82	1	1
SPHK1	-0.008	0.022	-9999	-10000	0	0
mol:S1P	-0.009	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	0.013	0.15	-9999	-0.67	11	11
GNAO1	-0.017	0.15	-9999	-0.73	20	20
PDGFB-D/PDGFRB/PLCgamma1	0.022	0.14	-9999	-0.57	11	11
PLCG1	0.019	0.14	-9999	-0.61	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GNAI1	0.012	0.039	-9999	-0.83	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.012	0.07	-9999	-0.64	5	5
S1P1/S1P	-0.016	0.065	-9999	-0.51	5	5
negative regulation of cAMP metabolic process	0.013	0.15	-9999	-0.52	18	18
MAPK3	0.005	0.2	-9999	-0.59	44	44
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.008	0.066	-9999	-0.83	3	3
PLCB2	0.03	0.07	-9999	-0.51	3	3
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.052	-9999	-0.42	5	5
receptor internalization	-0.015	0.06	-9999	-0.47	5	5
PTGS2	-0.038	0.34	-9999	-1.1	44	44
Rac1/GTP	-0.013	0.052	-9999	-0.48	3	3
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.066	-9999	-0.82	3	3
negative regulation of T cell proliferation	0.013	0.15	-9999	-0.52	18	18
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.005	-9999	-10000	0	0
MAPK1	0.005	0.2	-9999	-0.59	44	44
S1P1/S1P/PDGFB-D/PDGFRB	0.032	0.086	-9999	-0.51	6	6
ABCC1	0.014	0.002	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.006	0.024	-10000	0	-10000	0	0
AES	0.005	0.02	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	-0.026	0.17	-10000	0	-0.66	28	28
TLE1	0	0.067	-10000	0	-0.8	3	3
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.047	0.039	-10000	0	-10000	0	0
WIF1	-0.034	0.1	-10000	0	-0.31	58	58
beta catenin/RanBP3	0.022	0.091	0.37	25	-10000	0	25
KREMEN2	-0.009	0.082	-10000	0	-0.31	33	33
DKK1	-0.041	0.12	-10000	0	-0.32	79	79
beta catenin/beta TrCP1	0.053	0.037	-10000	0	-10000	0	0
FZD1	0.014	0.001	-10000	0	-10000	0	0
AXIN2	-0.047	0.31	-10000	0	-1.6	18	18
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.063	0.045	0.29	1	-0.41	1	2
Axin1/APC/GSK3	0.007	0.031	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.018	-10000	0	-10000	0	0
HNF1A	0.006	0.021	-10000	0	-10000	0	0
CTBP1	0.006	0.021	-10000	0	-10000	0	0
MYC	-0.032	0.26	-10000	0	-1.6	13	13
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.11	-10000	0	-0.55	19	19
NKD1	-0.013	0.14	-10000	0	-0.73	17	17
TCF4	0.006	0.021	-10000	0	-10000	0	0
TCF3	0.006	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.008	-10000	0	-10000	0	0
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.029	0.12	0.48	27	-10000	0	27
LEF1	-0.002	0.066	-10000	0	-0.42	9	9
DVL1	0.019	0.028	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.074	-10000	0	-0.48	4	4
DKK1/LRP6/Kremen 2	-0.037	0.078	-10000	0	-0.37	8	8
LRP6	0.014	0.001	-10000	0	-10000	0	0
CSNK1A1	0.006	0.023	-10000	0	-10000	0	0
NLK	0.014	0.004	-10000	0	-10000	0	0
CCND1	0	0.075	-10000	0	-0.81	1	1
WNT1	0.01	0.021	-10000	0	-0.31	2	2
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0	-10000	0	-10000	0	0
FRAT1	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.03	0.06	0.37	14	-10000	0	14
APC	0.039	0.026	-10000	0	-0.47	1	1
WNT1/LRP6/FZD1	0.035	0.036	-10000	0	-10000	0	0
CREBBP	0.006	0.021	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.001	0.034	0.3	1	-0.47	2	3
DAPP1	-0.054	0.14	-10000	0	-0.5	12	12
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.058	0.18	-10000	0	-0.57	19	19
mol:DAG	-0.005	0.096	-10000	0	-0.28	15	15
HRAS	0.013	0.021	-10000	0	-0.31	2	2
RAP1A	0.014	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.023	0.035	-10000	0	-0.46	1	1
PLCG2	0.013	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
ARF5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.014	0.27	1	-10000	0	1
ARF1/GTP	-0.001	0.022	0.28	1	-10000	0	1
RHOA	0.013	0	-10000	0	-10000	0	0
YES1	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP	0	0.013	0.26	1	-10000	0	1
ADAP1	0	0.013	0.26	1	-10000	0	1
ARAP3	0	0.014	0.27	1	-10000	0	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PREX1	0.013	0	-10000	0	-10000	0	0
ARHGEF6	0.012	0.038	-10000	0	-0.82	1	1
ARHGEF7	0.013	0	-10000	0	-10000	0	0
ARF1	0.013	0	-10000	0	-10000	0	0
NRAS	0.014	0.001	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
FGR	0.011	0.03	-10000	0	-0.31	4	4
mol:Ca2+	0.007	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.82	1	1
ZAP70	-0.022	0.16	-10000	0	-0.62	27	27
mol:IP3	0.005	0.072	-10000	0	-10000	0	0
LYN	0.013	0	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.035	-10000	0	-0.46	1	1
RhoA/GDP	-0.001	0.019	0.28	1	-10000	0	1
PDK1/Src/Hsp90	-0.003	0.036	-10000	0	-0.55	2	2
BLNK	0.013	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.038	0.038	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
PLEKHA2	0.023	0.041	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.8	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.015	0.3	1	-10000	0	1
RhoA/GTP	0	0.013	0.26	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.049	0.16	-10000	0	-0.61	13	13
BLK	-0.25	0.38	-10000	0	-0.76	163	163
PDPK1	0.01	0.054	-10000	0	-0.82	2	2
CYTH1	0	0.013	0.26	1	-10000	0	1
HCK	-0.008	0.08	-10000	0	-0.31	31	31
CYTH3	-0.002	0.034	0.26	1	-0.49	2	3
CYTH2	0	0.013	0.26	1	-10000	0	1
KRAS	0.014	0.001	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.014	0.096	-10000	0	-0.62	11	11
SGK1	-0.015	0.11	-10000	0	-0.69	11	11
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
mol:GDP	0.015	0.037	-10000	0	-0.49	1	1
SOS1	0.013	0	-10000	0	-10000	0	0
SYK	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.02	0.29	1	-10000	0	1
mol:PI-3-4-5-P3	0	0.018	0.37	1	-10000	0	1
ARAP3/RAP1A/GTP	0	0.013	0.26	1	-10000	0	1
VAV1	-0.013	0.1	-10000	0	-0.36	34	34
mol:PI-3-4-P2	0.013	0.049	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0	0.006	-10000	0	-10000	0	0
PLEKHA1	0.023	0.041	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.035	-10000	0	-0.46	1	1
LAT	0.006	0.077	-10000	0	-0.72	5	5
Rac1/GTP	-0.007	0.055	-10000	0	-0.47	2	2
ITK	-0.056	0.14	-10000	0	-0.44	59	59
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.014	0.13	-10000	0	-0.4	15	15
LCK	-0.01	0.11	-10000	0	-0.44	25	25
BTK	-0.014	0.062	0.26	1	-0.44	8	9

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.039	0.022	-9999	-10000	0	0
PLK1	0.11	0.11	-9999	-0.73	1	1
CDKN1B	0.15	0.048	-9999	-0.39	1	1
FOXO3	0.11	0.11	-9999	-0.58	4	4
KAT2B	0.025	0.01	-9999	-10000	0	0
FOXO1/SIRT1	0.009	0.038	-9999	-0.59	1	1
CAT	0.1	0.15	-9999	-1.4	3	3
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.028	0.011	-9999	-10000	0	0
FOXO1	0.042	0.015	-9999	-10000	0	0
MAPK10	0.043	0.026	-9999	-0.51	1	1
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.11	0.064	-9999	-0.48	4	4
response to oxidative stress	0.015	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	0.01	0.087	-9999	-0.72	3	3
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.002	-9999	-10000	0	0
BCL2L11	0.041	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.039	0.051	-9999	-0.5	4	4
mol:GDP	0.015	0.013	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.062	-9999	-0.5	3	3
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.041	0.041	-9999	-10000	0	0
MST1	0.023	0.042	-9999	-0.55	2	2
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.064	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.035	0.073	-9999	-0.49	9	9
MAPK9	0.044	0.007	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.005	0.043	-9999	-0.82	1	1
SOD2	0.16	0.073	-9999	-0.79	1	1
RBL2	0.11	0.15	-9999	-1.4	4	4
RAL/GDP	0.034	0.012	-9999	-10000	0	0
CHUK	0.025	0.01	-9999	-10000	0	0
Ran/GTP	0.015	0.002	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.043	0.01	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.066	0.39	-9999	-1.5	32	32
SKP2	0.006	0.076	-9999	-0.82	4	4
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.025	0.01	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.73	1	1
FOXO1-3a-4/beta catenin	-0.003	0.05	-9999	-0.42	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.051	-9999	-0.5	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.006	0.13	-9999	-0.82	11	11
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.003	-9999	-10000	0	0
ZFAND5	0.11	0.053	-9999	-0.47	1	1
SFN	-0.21	0.19	-9999	-0.34	310	310
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.017	0.062	-9999	-0.32	4	4
CREBBP	0.014	0.003	-9999	-10000	0	0
FBXO32	0.11	0.11	-9999	-0.73	1	1
BCL6	0.12	0.1	-9999	-0.69	4	4
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

Canonical 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.072	0.054	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	-0.028	0.078	-9999	-0.63	2	2
NFKBIA	0.049	0.024	-9999	-0.48	1	1
BIRC2	0.013	0	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.005	0.021	-9999	-10000	0	0
IKK complex/A20	-0.05	0.13	-9999	-0.64	2	2
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.039	-9999	-0.43	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.002	0.014	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.002	0.035	-9999	-0.55	2	2
NOD2	-0.032	0.12	-9999	-0.33	63	63
NFKB1	0.015	0.038	-9999	-0.82	1	1
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.012	0.038	-9999	-0.82	1	1
TNF/TNFR1A	-0.079	0.21	-9999	-0.63	58	58
TRAF6	0.01	0.054	-9999	-0.82	2	2
PRKCA	-0.025	0.18	-9999	-0.82	22	22
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.092	0.27	-9999	-0.82	58	58
NF kappa B1 p50/RelA	-0.001	0.024	-9999	-0.53	1	1
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.049	0.024	-9999	-0.47	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.003	0.016	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.02	0.084	-9999	-0.54	1	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.027	0.048	-9999	-0.63	1	1
CLOCK	-0.04	0.2	-9999	-0.83	29	29
TIMELESS/CRY2	-0.006	0.066	-9999	-10000	0	0
DEC1/BMAL1	-0.021	0.064	-9999	-10000	0	0
ATR	0.012	0.038	-9999	-0.82	1	1
NR1D1	-0.06	0.13	-9999	-10000	0	0
ARNTL	-0.02	0.097	-9999	-0.32	46	46
TIMELESS	-0.014	0.074	-9999	-10000	0	0
NPAS2	0.009	0.041	-9999	-0.56	2	2
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.008	0.031	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.008	0.031	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.03	0.15	-9999	-0.56	30	30
BMAL1/CLOCK	-0.056	0.15	-9999	-0.62	15	15
S phase of mitotic cell cycle	-0.027	0.048	-9999	-0.63	1	1
TIMELESS/CHEK1/ATR	-0.027	0.049	-9999	-0.64	1	1
mol:NADPH	-0.008	0.031	-9999	-10000	0	0
PER1/TIMELESS	-0.006	0.066	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.015	-9999	-0.31	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.086	-9999	-0.44	14	14
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.006	0.076	-9999	-0.82	4	4
ITGA4	0.004	0.069	-9999	-0.41	11	11
alpha4/beta7 Integrin/MAdCAM1	-0.031	0.098	-9999	-0.5	16	16
EPO	0.002	0.039	-9999	-0.31	7	7
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.62	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.049	-9999	-0.63	2	2
EPO/EPOR (dimer)	-0.007	0.037	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.038	-9999	-0.47	3	3
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PI3K	-0.004	0.05	-9999	-0.63	3	3
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.024	0.049	-9999	-0.5	3	3
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.011	0.09	-9999	-0.35	28	28
cell adhesion	-0.031	0.097	-9999	-0.49	16	16
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.023	0.077	-9999	-0.57	6	6
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.013	0.079	-9999	-0.55	8	8
p130Cas/Crk/Dock1	0.04	0.079	-9999	-0.45	10	10
VCAM1	0.001	0.092	-9999	-0.55	11	11
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.036	-9999	-0.5	2	2
BCAR1	0.031	0.073	-9999	-0.53	6	6
EPOR	0.007	0.047	-9999	-0.31	10	10
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.039	-9999	-0.48	3	3

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.012	0.056	0.29	17	-10000	0	17
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-10000	0	-0.56	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
RhoA/GTP	-0.012	0.057	-10000	0	-0.3	17	17
negative regulation of cAMP metabolic process	0.022	0.071	-10000	0	-0.33	17	17
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	0.007	0.054	-10000	0	-0.38	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.071	-10000	0	-0.34	17	17
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.72	20	20
CDC42/GTP	-0.011	0.055	-9999	-0.3	17	17
PLCG1	0.03	0.065	-9999	-0.31	17	17
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.011	0.054	-9999	-0.29	17	17
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
MAPK3	0.03	0.065	-9999	-0.33	1	1
MAPK1	0.03	0.065	-9999	-0.31	17	17
S1P/S1P5/Gi	0.022	0.071	-9999	-0.34	17	17
GNAI1	0.012	0.038	-9999	-0.82	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-9999	-0.56	1	1
RHOA	0.032	0.016	-9999	-10000	0	0
S1P/S1P4/Gi	0.023	0.069	-9999	-0.33	17	17
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.001	0.014	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

EPO signaling 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
BCL2L1	0.052	0.1	-9999	-10000	0	0
CRKL	0.038	0.045	-9999	-0.53	1	1
mol:DAG	0.042	0.05	-9999	-10000	0	0
HRAS	0.062	0.042	-9999	-10000	0	0
MAPK8	0.02	0.086	-9999	-0.57	9	9
RAP1A	0.038	0.045	-9999	-0.53	1	1
GAB1	0.038	0.045	-9999	-0.53	1	1
MAPK14	0.03	0.031	-9999	-10000	0	0
EPO	0.005	0.039	-9999	-0.3	7	7
PLCG1	0.042	0.05	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.009	0.047	-9999	-0.32	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.037	0.13	-9999	-0.57	27	27
GAB1/SHC/GRB2/SOS1	-0.005	0.025	-9999	-0.46	1	1
EPO/EPOR (dimer)	0.013	0.042	-9999	-10000	0	0
IRS2	0.038	0.045	-9999	-0.53	1	1
STAT1	0.042	0.077	-9999	-10000	0	0
STAT5B	0.043	0.065	-9999	-10000	0	0
cell proliferation	0.028	0.082	-9999	-0.53	9	9
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.008	0.034	-9999	-10000	0	0
TEC	0.038	0.045	-9999	-0.53	1	1
SOCS3	-0.034	0.19	-9999	-0.8	28	28
STAT1 (dimer)	0.042	0.076	-9999	-10000	0	0
JAK2	0.013	0.039	-9999	-0.84	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.043	0.051	-9999	-0.57	1	1
EPO/EPOR	0.013	0.042	-9999	-10000	0	0
LYN	0.014	0.004	-9999	-10000	0	0
TEC/VAV2	0.046	0.044	-9999	-0.51	1	1
elevation of cytosolic calcium ion concentration	0.009	0.047	-9999	-0.32	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.028	0.036	-9999	-10000	0	0
mol:IP3	0.042	0.05	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.01	0.033	-9999	-0.48	1	1
SH2B3	0.014	0.005	-9999	-10000	0	0
NFKB1	0.029	0.039	-9999	-0.51	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.019	0.069	-9999	-0.29	28	28
PTPN6	0.031	0.047	-9999	-0.56	1	1
TEC/VAV2/GRB2	0.051	0.043	-9999	-0.49	1	1
EPOR	0.009	0.047	-9999	-0.32	10	10
INPP5D	-0.003	0.071	-9999	-0.31	24	24
mol:GDP	-0.005	0.025	-9999	-0.47	1	1
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
CRKL/CBL/C3G	0.051	0.043	-9999	-0.49	1	1
VAV2	0.038	0.045	-9999	-0.53	1	1
CBL	0.038	0.045	-9999	-0.53	1	1
SHC/Grb2/SOS1	-0.006	0.028	-9999	-0.49	1	1
STAT5A	0.043	0.065	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.053	0.097	-9999	-10000	0	0
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
BTK	0.021	0.088	-9999	-0.5	8	8
BCL2	0.003	0.28	-9999	-0.98	35	35

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.063	0.16	-9999	-0.5	59	59
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.05	0.14	-9999	-0.42	59	59
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.025	0.067	-9999	-10000	0	0
YY1/LSF	0.028	0.051	-9999	-0.53	4	4
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.014	0.13	-9999	-0.37	58	58
I kappa B alpha/HDAC1	-0.001	0.091	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	-0.004	0.12	-9999	-0.32	58	58
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	-0.001	0.091	-9999	-10000	0	0
NuRD/MBD3 Complex	0.049	0.02	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.001	0.11	-9999	-0.48	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
GATA1	0.009	0.006	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.022	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.008	0.066	-9999	-0.82	3	3
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	-0.008	0.1	-9999	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.044	0.028	-9999	-10000	0	0
SIN3 complex	-0.001	0.023	-9999	-0.5	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.014	0.085	-9999	-10000	0	0
YY1/HDAC2	0.033	0	-9999	-10000	0	0
YY1/HDAC1	0.033	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.049	0.02	-9999	-10000	0	0
PPARG	-0.061	0.16	-9999	-0.46	63	63
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.001	0.091	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.022	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	-0.008	0.1	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.032	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.028	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.044	-9999	-0.48	4	4
YY1/SAP30/HDAC1	-0.001	0.022	-9999	-0.48	1	1
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.027	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.1	-9999	-10000	0	0
histone deacetylation	0.049	0.02	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.086	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	-0.001	0.092	-9999	-10000	0	0
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	-0.01	0.091	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.079	0.21	-9999	-0.63	58	58
SIN3/HDAC complex/Mad/Max	0.049	0.023	-9999	-10000	0	0
NuRD Complex	0.058	0.022	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.025	0.066	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0.032	0	-9999	-10000	0	0
HDAC complex	-0.003	0.039	-9999	-0.5	3	3
GATA1/Fog1	0	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.092	0.27	-9999	-0.82	58	58
negative regulation of cell growth	0.049	0.023	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.049	0.02	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.054	0.14	-9999	-0.44	58	58
SIN3/HDAC complex/NCoR1	0.046	0.027	-9999	-0.26	3	3
TFCP2	0.006	0.076	-9999	-0.82	4	4
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0.009	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.009	0.14	-9999	-0.56	30	30
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.039	-9999	-0.42	1	1
NFKBIA	0.024	0.037	-9999	-0.28	6	6
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.027	0.026	-9999	-0.55	1	1
ARRB2	0.018	0	-9999	-10000	0	0
REL	-0.039	0.2	-9999	-0.82	30	30
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.027	-9999	-0.55	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.026	-9999	-0.55	1	1
PIK3CA	0.008	0.066	-9999	-0.82	3	3
NF kappa B1 p50 dimer	0.02	0.03	-9999	-0.63	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.023	0.03	-9999	-0.63	1	1
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.039	-9999	-0.27	6	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.047	0.038	-9999	-0.4	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
PI3K	-0.004	0.05	-9999	-0.63	3	3
NF kappa B1 p50/RelA	0.031	0.039	-9999	-0.27	6	6
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	-0.004	0.029	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.009	0.14	-9999	-0.56	30	30
LCK	-0.01	0.11	-9999	-0.44	25	25
BCL3	0.013	0.015	-9999	-0.31	1	1

×

PLK1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.01	0.018	-9999	-10000	0	0
BUB1B	0.017	0.027	-9999	-0.15	1	1
PLK1	0.017	0.012	-9999	-10000	0	0
PLK1S1	0.015	0.007	-9999	-10000	0	0
KIF2A	0.023	0.03	-9999	-0.59	1	1
regulation of mitotic centrosome separation	0.017	0.012	-9999	-10000	0	0
GOLGA2	0.013	0	-9999	-10000	0	0
Hec1/SPC24	-0.002	0.076	-9999	-0.28	16	16
WEE1	0.023	0.011	-9999	-10000	0	0
cytokinesis	0.002	0.07	-9999	-0.29	5	5
PP2A-alpha B56	-0.018	0.059	-9999	-0.73	3	3
AURKA	0.016	0.009	-9999	-10000	0	0
PICH/PLK1	0.033	0.019	-9999	-10000	0	0
CENPE	0.019	0.049	-9999	-0.53	3	3
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.023	0.029	-9999	-0.58	1	1
PPP2CA	0.013	0	-9999	-10000	0	0
FZR1	0.013	0	-9999	-10000	0	0
TPX2	0.009	0.021	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
SPC24	-0.009	0.081	-9999	-0.31	32	32
FBXW11	0.013	0	-9999	-10000	0	0
CLSPN	0.005	0.035	-9999	-0.35	2	2
GORASP1	0.013	0	-9999	-10000	0	0
metaphase	0.001	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.009	0.007	-9999	-0.066	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.013	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-9999	-10000	0	0
spindle elongation	0.017	0.012	-9999	-10000	0	0
ODF2	0.013	0.001	-9999	-10000	0	0
BUB1	-0.027	0.068	-9999	-0.8	3	3
TPT1	0.015	0.007	-9999	-10000	0	0
CDC25C	0.011	0.023	-9999	-10000	0	0
CDC25B	0.012	0.026	-9999	-0.31	3	3
SGOL1	0.01	0.018	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.005	0.013	-9999	-10000	0	0
CDC14B	0.005	0.067	-9999	-0.65	5	5
CDC20	0.009	0.039	-9999	-0.31	7	7
PLK1/PBIP1	0.002	0.022	-9999	-10000	0	0
mitosis	0	0.002	-9999	-0.022	3	3
FBXO5	0.021	0.022	-9999	-0.4	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.033	0.11	-9999	-0.31	69	69
metaphase plate congression	0.015	0.007	-9999	-10000	0	0
ERCC6L	0.007	0.016	-9999	-10000	0	0
NLP/gamma Tubulin	0.013	0.009	-9999	-10000	0	0
microtubule cytoskeleton organization	0.015	0.007	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-9999	-0.011	3	3
PPP1R12A	0.013	0	-9999	-10000	0	0
interphase	0	0.001	-9999	-0.011	3	3
PLK1/PRC1-2	0.005	0.06	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0	0.004	-9999	-10000	0	0
RAB1A	0.013	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.018	0.039	-9999	-0.48	3	3
mitotic prometaphase	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.034	-9999	-0.32	2	2
microtubule-based process	-0.004	0.064	-9999	-10000	0	0
Golgi organization	0.017	0.012	-9999	-10000	0	0
Cohesin/SA2	-0.001	0.005	-9999	-10000	0	0
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.042	0.12	-9999	-0.31	81	81
APC/C/CDC20	0.021	0.024	-9999	-10000	0	0
PPP2R1A	0.013	0	-9999	-10000	0	0
chromosome segregation	0.002	0.022	-9999	-10000	0	0
PRC1	0.013	0	-9999	-10000	0	0
ECT2	0.022	0.039	-9999	-0.56	2	2
C13orf34	0.018	0.04	-9999	-0.48	3	3
NUDC	0.016	0.007	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.027	-9999	-0.15	1	1
spindle assembly	0.017	0.011	-9999	-10000	0	0
spindle stabilization	0.015	0.007	-9999	-10000	0	0
APC/C/HCDH1	0.013	0.059	-9999	-0.56	5	5
MKLP2/PLK1	-0.004	0.064	-9999	-10000	0	0
CCNB1	0.014	0.001	-9999	-10000	0	0
PPP1CB	0.013	0	-9999	-10000	0	0
BTRC	0.013	0	-9999	-10000	0	0
ROCK2	0.001	0.11	-9999	-0.52	21	21
TUBG1	0.015	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.009	-9999	-10000	0	0
MLF1IP	0.008	0.033	-9999	-10000	0	0
INCENP	0.009	0.054	-9999	-0.83	2	2

×

HIF-2-alpha transcription factor network

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
MMP14	-0.001	0.023	-10000	0	-10000	0	0
oxygen homeostasis	0.016	0.011	-10000	0	-10000	0	0
TCEB2	0.011	0.026	-10000	0	-0.31	3	3
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.011	0.074	-10000	0	-0.7	4	4
EPO	0.18	0.14	-10000	0	-0.8	2	2
FIH (dimer)	0.029	0.011	-10000	0	-10000	0	0
APEX1	0.027	0.011	-10000	0	-10000	0	0
SERPINE1	0.18	0.17	-10000	0	-0.8	3	3
FLT1	-0.002	0.072	-10000	0	-1.6	1	1
ADORA2A	0.19	0.14	-10000	0	-0.86	2	2
germ cell development	0.19	0.14	-10000	0	-0.85	2	2
SLC11A2	0.19	0.15	-10000	0	-0.89	2	2
BHLHE40	0.18	0.16	-10000	0	-0.89	2	2
HIF1AN	0.029	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.002	0.076	-10000	0	-0.97	2	2
ETS1	0.03	0.002	-10000	0	-10000	0	0
CITED2	-0.09	0.32	-10000	0	-1.2	37	37
KDR	-0.007	0.11	-10000	0	-1.4	3	3
PGK1	0.19	0.15	-10000	0	-0.89	2	2
SIRT1	0.012	0.038	-10000	0	-0.82	1	1
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.21	0.16	-10000	0	-1.2	2	2
EPAS1	0.11	0.1	-10000	0	-0.63	3	3
SP1	0.022	0.002	-10000	0	-10000	0	0
ABCG2	0.19	0.16	-10000	0	-0.88	4	4
EFNA1	0.19	0.15	-10000	0	-0.89	2	2
FXN	0.19	0.14	-10000	0	-0.86	2	2
POU5F1	0.19	0.15	-10000	0	-0.9	2	2
neuron apoptosis	-0.2	0.16	1.1	2	-10000	0	2
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	-0.002	0.14	-10000	0	-0.5	28	28
EGLN2	0.029	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.056	-10000	0	-0.82	2	2
VHL/Elongin B/Elongin C	-0.004	0.048	-10000	0	-0.6	3	3
VHL	0.008	0.066	-10000	0	-0.82	3	3
ARNT	0.027	0.011	-10000	0	-10000	0	0
SLC2A1	0.19	0.14	-10000	0	-0.86	2	2
TWIST1	0.18	0.17	-10000	0	-0.66	10	10
ELK1	0.015	0.026	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.001	0.067	-10000	0	-0.76	2	2
VEGFA	0.19	0.16	-10000	0	-0.84	4	4
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.032	0	-9999	-10000	0	0
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.032	0.009	-9999	-10000	0	0
MAPK12	0.02	0.078	-9999	-0.48	11	11
CCND1	0.017	0.034	-9999	-0.25	1	1
p38 gamma/SNTA1	0.025	0.074	-9999	-0.46	10	10
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.02	0.077	-9999	-0.48	11	11
MAP2K6	0.013	0.083	-9999	-0.53	11	11
MAPT	0.024	0.045	-9999	-0.4	3	3
MAPK13	0.024	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.017	0.021	-9999	-0.45	1	1

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.006	-10000	0	-10000	0	0
DOCK1	0.006	0.076	-10000	0	-0.82	4	4
ITGA4	0.004	0.069	-10000	0	-0.41	11	11
RAC1	0.013	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.12	-10000	0	-0.62	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.041	-10000	0	-0.55	2	2
alpha4/beta7 Integrin/Paxillin	-0.022	0.088	-10000	0	-0.5	14	14
lamellipodium assembly	-0.004	0.058	-10000	0	-0.54	5	5
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PI3K	-0.004	0.05	-10000	0	-0.63	3	3
ARF6	0.013	0	-10000	0	-10000	0	0
TLN1	0.013	0	-10000	0	-10000	0	0
PXN	0.024	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.03	-10000	0	-0.42	2	2
cell adhesion	-0.004	0.033	-10000	0	-0.46	2	2
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.004	0.036	-10000	0	-0.5	2	2
ITGB1	0.013	0	-10000	0	-10000	0	0
ITGB7	-0.02	0.14	-10000	0	-0.51	31	31
ARF6/GDP	0.001	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.01	0.067	-10000	0	-0.54	6	6
p130Cas/Crk/Dock1	-0.005	0.05	-10000	0	-0.55	4	4
VCAM1	0.001	0.092	-10000	0	-0.55	11	11
alpha4/beta1 Integrin/Paxillin/Talin	-0.004	0.033	-10000	0	-0.46	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.033	-10000	0	-0.46	2	2
BCAR1	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.033	0.46	2	-10000	0	2
CBL	0.013	0	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
GIT1	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.004	0.033	-10000	0	-0.46	2	2
Rac1/GTP	-0.005	0.068	-10000	0	-0.77	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.67	15	15
AKT1	0.085	0.085	-9999	-0.69	4	4
PTK2B	0.038	0.13	-9999	-0.96	4	4
VEGFR2 homodimer/Frs2	0.032	0.088	-9999	-1.1	3	3
CAV1	-0.009	0.14	-9999	-0.82	13	13
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.009	0.099	-9999	-0.87	5	5
endothelial cell proliferation	0.077	0.099	-9999	-0.63	4	4
mol:Ca2+	0.052	0.097	-9999	-1	3	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.009	0.094	-9999	-1.1	3	3
RP11-342D11.1	0.043	0.097	-9999	-0.73	6	6
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	-0.006	0.063	-9999	-0.59	5	5
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.008	0.066	-9999	-0.82	3	3
HRAS/GDP	-0.008	0.078	-9999	-0.76	4	4
SH2D2A	-0.033	0.18	-9999	-0.64	34	34
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.007	0.064	-9999	-0.72	3	3
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.034	0.14	-9999	-0.56	27	27
VEGFR1 homodimer	0.012	0.038	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.009	0.09	-9999	-1	3	3
GRB10	0.052	0.097	-9999	-1	3	3
PTPN11	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.089	-9999	-1	3	3
HRAS	0.012	0.021	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.041	0.075	-9999	-0.51	4	4
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.008	0.09	-9999	-1	3	3
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.085	-9999	-0.82	5	5
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.009	0.099	-9999	-0.87	5	5
mol:GDP	-0.008	0.082	-9999	-0.93	3	3
mol:NADP	0.078	0.062	-9999	-0.58	3	3
eNOS/Hsp90	0.08	0.058	-9999	-0.54	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.052	0.1	-9999	-1.1	3	3
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.066	-9999	-0.82	3	3
VEGFC	0.012	0.038	-9999	-0.82	1	1
FAK1/Vinculin	0.06	0.11	-9999	-0.83	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.024	0.13	-9999	-1	4	4
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.02	0.061	-9999	-0.65	3	3
mol:L-citrulline	0.078	0.062	-9999	-0.58	3	3
ITGAV	0.01	0.054	-9999	-0.82	2	2
PIK3CA	0.008	0.066	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.009	0.094	-9999	-1.1	3	3
VEGFR2 homodimer/VEGFA homodimer	-0.011	0.11	-9999	-1.2	3	3
VEGFR2/3 heterodimer	0.026	0.12	-9999	-0.95	6	6
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.054	0.11	-9999	-1.1	3	3
VEGFR2 homodimer	0.031	0.096	-9999	-1.2	3	3
FLT1	0.012	0.038	-9999	-0.82	1	1
NEDD4	0.012	0.054	-9999	-0.82	2	2
MAPK3	0.044	0.1	-9999	-0.96	3	3
MAPK1	0.044	0.1	-9999	-0.96	3	3
VEGFA145/NRP2	-0.02	0.072	-9999	-0.63	3	3
VEGFR1/2 heterodimer	0.031	0.1	-9999	-1.2	3	3
KDR	0.031	0.097	-9999	-1.2	3	3
VEGFA165/NRP1/VEGFR2 homodimer	-0.017	0.1	-9999	-1.2	3	3
SRC	0.013	0.015	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.046	0.1	-9999	-1	3	3
PI3K	-0.01	0.089	-9999	-0.96	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.009	0.099	-9999	-0.87	5	5
FES	0.052	0.11	-9999	-1.1	3	3
GAB1	-0.009	0.088	-9999	-0.99	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.099	-9999	-0.87	5	5
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.069	0.09	-9999	-0.63	3	3
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.009	0.099	-9999	-0.87	5	5
PI3K/GAB1	0.087	0.079	-9999	-0.72	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.008	0.089	-9999	-1	3	3
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.012	0.11	-9999	-0.83	7	7
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.052	0.11	-9999	-1.1	3	3
actin cytoskeleton reorganization	-0.034	0.14	-9999	-0.55	27	27
PTK2	0.054	0.12	-9999	-0.79	6	6
EDG1	0.043	0.097	-9999	-0.73	6	6
mol:DAG	0.052	0.1	-9999	-1.1	3	3
CaM/Ca2+	-0.008	0.084	-9999	-0.94	3	3
MAP2K3	0.052	0.12	-9999	-1.1	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.01	0.11	-9999	-1.2	3	3
PLCG1	0.052	0.11	-9999	-1.1	3	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.009	0.094	-9999	-1.1	3	3
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.01	0.11	-9999	-0.94	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.009	0.099	-9999	-0.87	5	5
cell migration	0.084	0.091	-9999	-0.72	3	3
mol:PI-3-4-5-P3	-0.009	0.077	-9999	-0.82	3	3
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	-0.008	0.084	-9999	-0.95	3	3
mol:NO	0.078	0.062	-9999	-0.58	3	3
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.077	-9999	-0.76	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.051	0.11	-9999	-1.2	3	3
VHL	0.008	0.066	-9999	-0.82	3	3
ITGB3	-0.011	0.14	-9999	-0.82	14	14
NOS3	0.08	0.071	-9999	-0.69	3	3
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.012	0.11	-9999	-0.72	8	8
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.037	0.15	-9999	-1.2	3	3
PRKCB	0.039	0.11	-9999	-0.94	3	3
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.042	0.1	-9999	-0.77	6	6
VEGFR1/2 heterodimer/VEGFA homodimer	-0.01	0.11	-9999	-0.94	5	5
VEGFA165/NRP2	-0.02	0.072	-9999	-0.63	3	3
MAPKKK cascade	-0.008	0.076	-9999	-0.85	3	3
NRP2	-0.012	0.088	-9999	-0.31	38	38
VEGFC homodimer	0.012	0.038	-9999	-0.82	1	1
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.06	0.11	-9999	-0.83	4	4
MAP3K13	0.044	0.13	-9999	-1.2	3	3
PDPK1	0.077	0.087	-9999	-0.74	4	4

×

PDGFR-beta signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.001	0.04	-9999	-0.74	1	1
PDGFB-D/PDGFRB/SLAP	-0.002	0.03	-9999	-0.64	1	1
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.026	-9999	-0.55	1	1
AKT1	0.059	0.044	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.051	-9999	-0.79	1	1
PIK3CA	0.008	0.066	-9999	-0.82	3	3
FGR	0.002	0.029	-9999	-0.56	1	1
mol:Ca2+	0.02	0.049	-9999	-0.82	1	1
MYC	0.018	0.15	-9999	-0.84	14	14
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.029	-9999	-0.45	1	1
LRP1/PDGFRB/PDGFB	-0.002	0.035	-9999	-0.55	2	2
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
GO:0007205	0.02	0.05	-9999	-0.85	1	1
PTEN	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.042	0.12	-9999	-0.31	82	82
PDGFB-D/PDGFRB/SHP2	-0.003	0.041	-9999	-0.64	2	2
PDGFB-D/PDGFRB/GRB10	-0.001	0.029	-9999	-0.64	1	1
cell cycle arrest	-0.002	0.03	-9999	-0.63	1	1
HRAS	0.012	0.021	-9999	-0.31	2	2
HIF1A	0.064	0.04	-9999	-10000	0	0
GAB1	0.013	0.064	-9999	-0.87	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.02	0.06	-9999	-0.78	1	1
PDGFB-D/PDGFRB	0.012	0.031	-9999	-0.57	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.029	-9999	-0.64	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.001	0.048	-9999	-0.75	1	1
positive regulation of MAPKKK cascade	-0.003	0.041	-9999	-0.64	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.02	0.05	-9999	-0.86	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.036	0.084	-9999	-0.8	1	1
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.18	0.28	-9999	-0.62	142	142
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.029	-9999	-0.64	1	1
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.017	0.071	-9999	-0.87	1	1
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.029	-9999	-0.64	1	1
LCK	-0.008	0.088	-9999	-0.73	6	6
PDGFRB	0.012	0.039	-9999	-0.83	1	1
ACP1	0.013	0	-9999	-10000	0	0
HCK	0.005	0.035	-9999	-0.55	1	1
ABL1	0.009	0.061	-9999	-0.83	1	1
PDGFB-D/PDGFRB/CBL	0.009	0.068	-9999	-0.95	1	1
PTPN1	0.014	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.006	0.049	-9999	-0.31	11	11
cell proliferation	0.02	0.14	-9999	-0.73	14	14
SLA	0.013	0.015	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.052	0.025	-9999	-0.43	1	1
SRC	0.005	0.029	-9999	-0.56	1	1
PI3K	-0.005	0.041	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.028	0.066	-9999	-0.7	1	1
SH2B2	0.013	0.015	-9999	-0.31	1	1
PLCgamma1/SPHK1	0.024	0.053	-9999	-0.83	1	1
LYN	0.006	0.029	-9999	-0.56	1	1
LRP1	0.012	0.038	-9999	-0.82	1	1
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.021	-9999	-0.45	1	1
SPHK1	0.007	0.049	-9999	-0.31	5	5
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.02	0.05	-9999	-0.86	1	1
PLCG1	0.02	0.052	-9999	-0.9	1	1
NHERF/PDGFRB	-0.002	0.027	-9999	-0.55	1	1
YES1	0.003	0.028	-9999	-0.56	1	1
cell migration	-0.002	0.027	-9999	-0.55	1	1
SHC/Grb2/SOS1	0	0.021	-9999	-0.45	1	1
SLC9A3R2	0.013	0	-9999	-10000	0	0
SLC9A3R1	0.012	0.021	-9999	-0.31	2	2
NHERF1-2/PDGFRB/PTEN	-0.003	0.033	-9999	-0.5	2	2
FYN	0.006	0.029	-9999	-0.56	1	1
DOK1	0.034	0.025	-9999	-0.5	1	1
HRAS/GTP	-0.001	0.014	-9999	-10000	0	0
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.027	0.09	-9999	-0.54	4	4
PRKCD	0.034	0.026	-9999	-0.51	1	1
FER	0.031	0.05	-9999	-0.51	4	4
MAPKKK cascade	-0.001	0.021	-9999	-0.44	1	1
RASA1	0.034	0.026	-9999	-0.51	1	1
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.017	0.03	-9999	-0.46	1	1
PDGFB-D/PDGFRB/SHB	-0.001	0.029	-9999	-0.64	1	1
chemotaxis	0.009	0.06	-9999	-0.79	1	1
STAT1-3-5/STAT1-3-5	-0.003	0.023	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.001	0.03	-9999	-0.65	1	1
PTPRJ	0.013	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

Figure S119. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S119. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.031	-9999	-0.39	3	3
TRAF2/ASK1	-0.001	0.025	-9999	-0.56	1	1
ATM	0.012	0.038	-9999	-0.82	1	1
MAP2K3	0.026	0.057	-9999	-0.53	2	2
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.025	0.078	-9999	-0.44	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.001	0.1	-9999	-0.67	10	10
TXN	0.009	0.006	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	-0.014	0.15	-9999	-0.82	16	16
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.029	-9999	-0.63	1	1
TAK1/TAB family	-0.001	0.014	-9999	-0.22	2	2
RAC1/OSM/MEKK3	0	0.006	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.033	-9999	-0.47	1	1
TRAF6	0.007	0.03	-9999	-0.46	2	2
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.005	0.085	-9999	-0.82	5	5
CCM2	0.013	0.015	-9999	-0.31	1	1
CaM/Ca2+/CAMKIIB	-0.006	0.056	-9999	-0.56	5	5
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.006	0.064	-9999	-0.6	5	5
OSM/MEKK3	0	0.009	-9999	-10000	0	0
TAOK1	-0.038	0.16	-9999	-0.46	57	57
TAOK2	0.017	0.021	-9999	-0.45	1	1
TAOK3	0.017	0.021	-9999	-0.45	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.026	-9999	-0.55	1	1
GADD45/MTK1/MTK1	-0.023	0.1	-9999	-0.49	22	22

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.045	0	-9999	-10000	0	0
SMAD3/SMAD4	0.049	0.02	-9999	-0.39	1	1
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.019	-9999	-0.42	1	1
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.022	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.037	0.15	-9999	-0.63	28	28
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	-0.035	0.2	-9999	-0.82	28	28
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.012	0.038	-9999	-0.82	1	1
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.023	-9999	-0.5	1	1
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC5	0	0	-9999	-10000	0	0
GATA2/HDAC5	0	0.009	-9999	-10000	0	0
HDAC5/BCL6/BCoR	-0.001	0.025	-9999	-0.55	1	1
HDAC9	-0.018	0.096	-9999	-0.31	46	46
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
HDAC4/RFXANK	-0.001	0.013	-9999	-10000	0	0
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.013	0	-9999	-10000	0	0
HDAC5	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.029	-9999	-0.63	1	1
Histones	0.036	0.023	-9999	-10000	0	0
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.013	-9999	-10000	0	0
CAMK4	-0.005	0.11	-9999	-0.54	16	16
Tubulin/HDAC6	-0.006	0.055	-9999	-0.55	5	5
SUMO1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.009	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0.032	0	-9999	-10000	0	0
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.007	0.064	-9999	-0.63	5	5
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.029	-9999	-0.63	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.011	0.068	-9999	-0.55	7	7
HDAC4/ER alpha	-0.043	0.14	-9999	-0.63	23	23
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.035	0.023	-9999	-10000	0	0
cell motility	-0.006	0.055	-9999	-0.54	5	5
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.012	0.038	-9999	-0.82	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.048	0.19	-9999	-0.53	54	54
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.012	0.038	-9999	-0.82	1	1
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.001	0.021	-9999	-0.46	1	1
GNG2	0.012	0.038	-9999	-0.82	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.005	0.085	-9999	-0.82	5	5
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.012	0.021	-9999	-0.31	2	2
nuclear import	0	0	-9999	-10000	0	0

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.028	0.007	-9999	-10000	0	0
BIRC5	-0.016	0.098	-9999	-0.33	42	42
NFKBIA	0.032	0.008	-9999	-10000	0	0
CPEB1	-0.048	0.22	-9999	-0.82	35	35
AKT1	0.032	0.008	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.011	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.013	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.013	0.005	-9999	-10000	0	0
PAK1/Aurora A	0.028	0.007	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.012	0.038	-9999	-0.82	1	1
TPX2	0.002	0.067	-9999	-10000	0	0
TP53	0.032	0.006	-9999	-10000	0	0
DLG7	0.021	0.008	-9999	-10000	0	0
AURKAIP1	0.012	0.021	-9999	-0.31	2	2
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.003	0.014	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.011	-9999	-10000	0	0
AURKA	0.026	0.011	-9999	-10000	0	0
AURKB	-0.014	0.027	-9999	-0.14	3	3
CDC25B	0.007	0.018	-9999	-10000	0	0
G2/M transition checkpoint	0.002	0.025	-9999	-0.5	1	1
mRNA polyadenylation	-0.034	0.13	-9999	-0.5	35	35
Aurora A/CPEB	-0.034	0.13	-9999	-0.5	35	35
Aurora A/TACC1/TRAP/chTOG	0.003	0.026	-9999	-0.47	1	1
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.028	0.007	-9999	-10000	0	0
regulation of centrosome cycle	0.002	0.011	-9999	-10000	0	0
spindle assembly	0.002	0.024	-9999	-0.46	1	1
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.01	0.036	-9999	-0.45	1	1
CENPA	-0.009	0.026	-9999	-0.26	3	3
Aurora A/PP2A	0.028	0.007	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.008	-9999	-10000	0	0
negative regulation of DNA binding	0.031	0.006	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	0.002	0.026	-9999	-0.5	1	1
mitotic prometaphase	0.005	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.011	-9999	-10000	0	0
TACC1	0.012	0.038	-9999	-0.82	1	1
TACC3	0.013	0.015	-9999	-0.31	1	1
Aurora A/Antizyme1	0.003	0.016	-9999	-10000	0	0
Aurora A/RasGAP	0.028	0.007	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.005	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.002	0.067	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.02	0.049	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.06	0.13	-10000	0	-10000	0	0
regulation of axonogenesis	-0.01	0.037	0.32	2	-10000	0	2
myoblast fusion	0.023	0.052	-10000	0	-10000	0	0
mol:GTP	-0.026	0.039	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.094	0.11	0.52	1	-10000	0	1
ARF1/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GM1	-0.011	0.033	-10000	0	-10000	0	0
mol:Choline	0.012	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.002	0.064	-10000	0	-10000	0	0
MAPK3	-0.017	0.065	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.094	0.11	-10000	0	-0.52	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.023	0.052	-10000	0	-10000	0	0
ARF1/GDP	0.005	0.059	-10000	0	-10000	0	0
ARF6	-0.001	0.023	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.18	0.17	-10000	0	-0.33	112	112
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.017	0.065	-10000	0	-10000	0	0
actin filament bundle formation	0.025	0.038	-10000	0	-10000	0	0
KALRN	-0.005	0.051	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.025	0.038	-10000	0	-10000	0	0
NME1	0.011	0.007	-10000	0	-10000	0	0
Rac1/GDP	-0.025	0.038	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.026	0.039	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.002	0.064	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.026	0.039	-10000	0	-10000	0	0
ARF6/GTP	-0.026	0.039	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GDP	-0.01	0.065	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.01	0.014	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0.001	0.033	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.002	0.064	-10000	0	-10000	0	0
ruffle organization	0.01	0.037	-10000	0	-0.32	2	2
regulation of epithelial cell migration	-0.026	0.039	-10000	0	-10000	0	0
PLD2	0.001	0.033	-10000	0	-10000	0	0
PIP5K1A	0.01	0.037	-10000	0	-0.33	2	2
mol:Phosphatidic acid	0.012	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.002	0.064	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.051	0.039	-10000	0	-0.44	3	3
adherens junction organization	0.041	0.037	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.053	0.057	-10000	0	-0.74	1	1
FMN1	0.022	0.11	-10000	0	-0.44	25	25
mol:IP3	-0.003	0.032	-10000	0	-0.41	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.012	-10000	0	-10000	0	0
CTNNB1	0.013	0	-10000	0	-10000	0	0
AKT1	0.049	0.036	-10000	0	-0.4	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.046	0.006	-10000	0	-10000	0	0
CTNND1	0.014	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.036	-10000	0	-0.49	2	2
VASP	0.047	0.012	-10000	0	-10000	0	0
ZYX	0.047	0.012	-10000	0	-10000	0	0
JUB	0.046	0.025	-10000	0	-0.44	1	1
EGFR(dimer)	0.042	0.048	-10000	0	-0.47	4	4
E-cadherin/beta catenin-gamma catenin	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.034	-10000	0	-0.43	3	3
PIK3CA	0.009	0.066	-10000	0	-0.82	3	3
PI3K	-0.003	0.034	-10000	0	-0.44	3	3
FYN	0.051	0.035	-10000	0	-0.35	3	3
mol:Ca2+	-0.002	0.031	-10000	0	-0.4	3	3
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.003	0.032	-10000	0	-0.41	3	3
CDH1	0.013	0	-10000	0	-10000	0	0
RhoA/GDP	0.053	0.057	-10000	0	-0.47	4	4
establishment of polarity of embryonic epithelium	0.046	0.011	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.006	0.076	-10000	0	-0.82	4	4
CASR	0.042	0.037	-10000	0	-0.38	3	3
RhoA/GTP	-0.002	0.029	-10000	0	-0.36	3	3
AKT2	0.049	0.036	-10000	0	-0.4	3	3
actin cable formation	0.029	0.11	-10000	0	-0.42	25	25
apoptosis	0.003	0.033	0.41	3	-10000	0	3
CTNNA1	0.014	0.001	-10000	0	-10000	0	0
mol:GDP	0.047	0.062	-10000	0	-0.48	6	6
PIP5K1A	0.045	0.037	-10000	0	-0.5	2	2
PLCG1	-0.003	0.033	-10000	0	-0.42	3	3
Rac1/GTP	-0.004	0.039	-10000	0	-0.42	4	4
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.033	-9999	-0.31	5	5
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.022	0.023	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.044	0.007	-9999	-10000	0	0
KLHL20	-0.009	0.021	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.074	0.009	-9999	-10000	0	0
ENAH	0.044	0.007	-9999	-10000	0	0
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	0	0.002	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.001	0.014	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.081	-9999	-0.5	12	12
RAPGEF1	0.058	0.006	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.052	0.006	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.024	0.1	-9999	-0.63	12	12
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.045	0.002	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.016	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.08	0.072	-9999	-0.5	1	1
PI3K	-0.002	0.021	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.17	0.16	-9999	-0.82	1	1
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	-0.001	0.012	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.074	0.009	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.016	-9999	-10000	0	0
CDC42/GDP	0.074	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.027	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.073	0.01	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.002	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.013	0.032	-9999	-0.15	10	10
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.044	0.007	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0.002	-9999	-10000	0	0
WASF2	0.002	0.008	-9999	-10000	0	0
Rap1/GTP	0	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.016	0.075	-9999	-0.46	12	12
CCND1	0.015	0.038	-9999	-0.18	10	10
VAV2	0.056	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.045	0.001	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.015	0.071	-9999	-0.44	12	12
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.044	0.009	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
Rac1/GTP	-0.017	0.033	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

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	-0.021	0.16	-10000	0	-0.73	22	22
CLTC	0.034	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.029	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0	0	-10000	0	-10000	0	0
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.031	0	-10000	0	-10000	0	0
CPE	0.012	0.069	-10000	0	-0.56	7	7
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0.028	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0	-10000	0	-10000	0	0
TSHR	0.018	0.037	-10000	0	-0.56	2	2
INS	0.013	0	-10000	0	-10000	0	0
BIN1	0.013	0	-10000	0	-10000	0	0
mol:Choline	0.028	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.031	0	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.023	-10000	0	-0.5	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.031	0	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0.015	-10000	0	-0.31	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.008	-10000	0	-10000	0	0
ACAP1	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.026	0.001	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.002	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.046	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.02	0	-10000	0	-10000	0	0
clathrin coat assembly	0.034	0	-10000	0	-10000	0	0
IL2RA	0.011	0.07	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.016	0.078	-10000	0	-0.41	18	18
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0	-10000	0	-10000	0	0
SDC1	0.03	0.008	-10000	0	-10000	0	0
ARF6/GDP	0.019	0	-10000	0	-10000	0	0
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.028	0	-10000	0	-10000	0	0
endocytosis	0.001	0.023	0.5	1	-10000	0	1
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.028	0.078	-10000	0	-0.44	13	13
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.012	0.038	-10000	0	-0.82	1	1
Dynamin 2/GDP	0.027	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.031	0.069	-10000	0	-0.44	10	10
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.032	-9999	-9999
HDAC4	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.013	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.013	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.013	-9999	-9999
SUMO1/HDAC4	0.032	-9999	-9999
SUMO1/HDAC1	0.032	-9999	-9999
RANGAP1	0.013	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.013	-9999	-9999
UBE2I	0.013	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.013	-9999	-9999
PIAS1	0.013	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

E-cadherin signaling events

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	0	-9999	-9999
E-cadherin/beta catenin	0	-9999	-9999
CTNNB1	0.013	-9999	-9999
JUP	0.013	-9999	-9999
CDH1	0.013	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.001	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.015	-9999	-0.21	2	2
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.004	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0	-9999	-10000	0	0
CD4	0.003	0.057	-9999	-10000	0	0
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.002	0.028	-9999	-0.43	2	2
ARF1/GTP	-0.001	0.016	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.002	0.027	-9999	-0.42	2	2
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	-0.002	0.028	-9999	-0.43	2	2
ARF1/GDP	0	0.007	-9999	-10000	0	0
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARFIP2	0	0.005	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.027	0.008	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	-0.001	0.01	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.029	0	-9999	-10000	0	0
ARF1/GDP/Membrin	-0.001	0.009	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.004	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.036	0.014	-9999	-10000	0	0
PLD2	-0.002	0.027	-9999	-0.43	2	2
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	-0.002	0.028	-9999	-0.43	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.001	0.015	-9999	-0.24	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.002	0.027	-9999	-0.42	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	-0.001	0.011	-9999	-0.17	2	2
USO1	-0.001	0.011	-9999	-0.17	2	2
GBF1	-0.001	0.011	-9999	-0.17	2	2
ARF1/GTP/Arfaptin 2	0	0.003	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.027	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.029	-9999	-0.63	1	1
RELB	0.013	0	-9999	-10000	0	0
NFKB2	0.013	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.MK.A4N9	TCGA.MK.A4N7	TCGA.MK.A4N6	TCGA.L6.A4EU
109_MAP3K5	-0.28	-0.017	-0.017	-0.017
47_PPARGC1A	-0.82	-0.82	-0.82	0.013
105_BMP4	0.013	-0.31	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	0.013	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	-0.5	-0.5	-0.5	-0.5
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.013
84_STAT5B	0.047	-0.097	0	-0.097
84_STAT5A	0.047	-0.097	0	-0.097