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

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	253
Signaling events mediated by Stem cell factor receptor (c-Kit)	166
Signaling events regulated by Ret tyrosine kinase	153
TCGA08_retinoblastoma	138
Reelin signaling pathway	135
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	122
Wnt signaling	107
FOXA2 and FOXA3 transcription factor networks	100
PDGFR-alpha signaling pathway	98
Noncanonical Wnt signaling pathway	93

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	0.5121	253	1775	7	-0.52	0	1000	-1000	-0.034	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3360	166	12967	78	-0.8	0.24	1000	-1000	-0.067	-1000
Signaling events regulated by Ret tyrosine kinase	0.3097	153	12554	82	-0.46	0.013	1000	-1000	-0.078	-1000
TCGA08_retinoblastoma	0.2794	138	1104	8	-0.12	0.071	1000	-1000	-0.018	-1000
Reelin signaling pathway	0.2733	135	7575	56	-0.59	0.033	1000	-1000	-0.075	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2470	122	8320	68	-0.9	0.37	1000	-1000	-0.12	-1000
Wnt signaling	0.2166	107	750	7	-0.41	0.013	1000	-1000	-0.029	-1000
FOXA2 and FOXA3 transcription factor networks	0.2024	100	4602	46	-0.91	0.021	1000	-1000	-0.031	-1000
PDGFR-alpha signaling pathway	0.1984	98	4337	44	-0.49	0.033	1000	-1000	-0.057	-1000
Noncanonical Wnt signaling pathway	0.1883	93	2434	26	-0.41	0.013	1000	-1000	-0.081	-1000
IL4-mediated signaling events	0.1883	93	8549	91	-1.3	0.67	1000	-1000	-0.13	-1000
Signaling events mediated by the Hedgehog family	0.1761	87	4542	52	-0.38	0.2	1000	-1000	-0.069	-1000
Nongenotropic Androgen signaling	0.1700	84	4374	52	-0.34	0.16	1000	-1000	-0.059	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1599	79	4290	54	-0.59	0.028	1000	-1000	-0.089	-1000
Calcium signaling in the CD4+ TCR pathway	0.1599	79	2456	31	-0.52	0.013	1000	-1000	-0.076	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1518	75	2561	34	-0.17	0.013	1000	-1000	-0.052	-1000
Glypican 1 network	0.1316	65	3124	48	-0.38	0.028	1000	-1000	-0.042	-1000
HIF-1-alpha transcription factor network	0.1296	64	4930	76	-0.57	0.041	1000	-1000	-0.081	-1000
Endothelins	0.1255	62	6001	96	-0.39	0.013	1000	-1000	-0.084	-1000
IGF1 pathway	0.1255	62	3580	57	-0.19	0.058	1000	-1000	-0.089	-1000
Glucocorticoid receptor regulatory network	0.1194	59	6818	114	-0.55	0.36	1000	-1000	-0.063	-1000
Ephrin B reverse signaling	0.1134	56	2728	48	-0.3	0.18	1000	-1000	-0.067	-1000
TCR signaling in naïve CD8+ T cells	0.1134	56	5266	93	-0.2	0.087	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.1134	56	3408	60	-0.31	0.019	1000	-1000	-0.14	-1000
Glypican 2 network	0.1073	53	212	4	-0.087	-0.009	1000	-1000	-0.03	-1000
BMP receptor signaling	0.1012	50	4123	81	-0.57	0.026	1000	-1000	-0.094	-1000
Coregulation of Androgen receptor activity	0.0992	49	3750	76	-0.77	0.062	1000	-1000	-0.051	-1000
Arf6 signaling events	0.0972	48	2986	62	-0.32	0.02	1000	-1000	-0.063	-1000
Syndecan-1-mediated signaling events	0.0951	47	1625	34	-0.2	0.013	1000	-1000	-0.059	-1000
IL12-mediated signaling events	0.0830	41	3594	87	-0.4	0.025	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0830	41	3524	85	-0.3	0.15	1000	-1000	-0.087	-1000
Syndecan-4-mediated signaling events	0.0810	40	2743	67	-0.25	0.022	1000	-1000	-0.086	-1000
Hedgehog signaling events mediated by Gli proteins	0.0789	39	2551	65	-0.66	0.061	1000	-1000	-0.055	-1000
amb2 Integrin signaling	0.0789	39	3201	82	-0.24	0.013	1000	-1000	-0.071	-1000
Signaling mediated by p38-alpha and p38-beta	0.0789	39	1732	44	-0.23	0.013	1000	-1000	-0.049	-1000
IL6-mediated signaling events	0.0769	38	2924	75	-0.2	0.059	1000	-1000	-0.082	-1000
EGFR-dependent Endothelin signaling events	0.0688	34	727	21	-0.11	0.013	1000	-1000	-0.072	-1000
Thromboxane A2 receptor signaling	0.0648	32	3434	105	-0.22	0.034	1000	-1000	-0.07	-1000
FAS signaling pathway (CD95)	0.0607	30	1448	47	-0.23	0.03	1000	-1000	-0.042	-1000
TCGA08_p53	0.0587	29	204	7	-0.08	0.051	1000	-1000	-0.009	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0567	28	2447	85	-0.27	0.013	1000	-1000	-0.074	-1000
Regulation of Androgen receptor activity	0.0567	28	2002	70	-0.48	0.034	1000	-1000	-0.071	-1000
Syndecan-2-mediated signaling events	0.0547	27	1907	69	-0.22	0.038	1000	-1000	-0.055	-1000
Regulation of p38-alpha and p38-beta	0.0547	27	1477	54	-0.47	0.013	1000	-1000	-0.059	-1000
IL27-mediated signaling events	0.0547	27	1396	51	-0.15	0.067	1000	-1000	-0.082	-1000
Visual signal transduction: Rods	0.0547	27	1406	52	-0.2	0.015	1000	-1000	-0.078	-1000
Plasma membrane estrogen receptor signaling	0.0526	26	2305	86	-0.18	0.021	1000	-1000	-0.077	-1000
Ras signaling in the CD4+ TCR pathway	0.0526	26	450	17	-0.089	0.013	1000	-1000	-0.044	-1000
ErbB2/ErbB3 signaling events	0.0506	25	1672	65	-0.12	0.027	1000	-1000	-0.062	-1000
Osteopontin-mediated events	0.0506	25	971	38	-0.26	0.013	1000	-1000	-0.11	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0506	25	1346	52	-0.28	0.053	1000	-1000	-0.06	-1000
BCR signaling pathway	0.0506	25	2508	99	-0.19	0.023	1000	-1000	-0.089	-1000
LPA receptor mediated events	0.0486	24	2547	102	-0.25	0.031	1000	-1000	-0.086	-1000
VEGFR1 specific signals	0.0486	24	1398	56	-0.07	0.041	1000	-1000	-0.07	-1000
JNK signaling in the CD4+ TCR pathway	0.0466	23	392	17	-0.1	0.018	1000	-1000	-0.061	-1000
Signaling events mediated by PTP1B	0.0466	23	1766	76	-0.24	0.021	1000	-1000	-0.074	-1000
Integrins in angiogenesis	0.0466	23	1995	84	-0.23	0.033	1000	-1000	-0.089	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0466	23	2062	88	-0.32	0.03	1000	-1000	-0.11	-1000
p75(NTR)-mediated signaling	0.0425	21	2729	125	-0.35	0.066	1000	-1000	-0.093	-1000
Regulation of nuclear SMAD2/3 signaling	0.0405	20	2769	136	-0.34	0.064	1000	-1000	-0.067	-1000
Aurora C signaling	0.0405	20	144	7	-0.061	0	1000	-1000	-0.039	-1000
Fc-epsilon receptor I signaling in mast cells	0.0405	20	2010	97	-0.2	0.03	1000	-1000	-0.076	-1000
FOXM1 transcription factor network	0.0385	19	981	51	-0.18	0.053	1000	-1000	-0.14	-1000
Visual signal transduction: Cones	0.0364	18	715	38	-0.088	0.013	1000	-1000	-0.069	-1000
ErbB4 signaling events	0.0344	17	1226	69	-0.14	0.057	1000	-1000	-0.085	-1000
IL1-mediated signaling events	0.0344	17	1106	62	-0.12	0.066	1000	-1000	-0.084	-1000
TCGA08_rtk_signaling	0.0344	17	458	26	-0.24	0.025	1000	-1000	-0.018	-1000
Aurora B signaling	0.0344	17	1165	67	-0.38	0.014	1000	-1000	-0.066	-1000
Insulin-mediated glucose transport	0.0324	16	513	32	-0.21	0.042	1000	-1000	-0.059	-1000
Syndecan-3-mediated signaling events	0.0324	16	568	35	-0.16	0.013	1000	-1000	-0.073	-1000
Effects of Botulinum toxin	0.0324	16	426	26	-0.16	0.019	1000	-1000	-0.061	-1000
Rapid glucocorticoid signaling	0.0324	16	338	20	-0.094	0.015	1000	-1000	-0.037	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0324	16	1992	120	-0.31	0.042	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0304	15	187	12	-0.12	0.015	1000	-1000	-0.021	-1000
Presenilin action in Notch and Wnt signaling	0.0304	15	939	61	-0.2	0.042	1000	-1000	-0.076	-1000
Ceramide signaling pathway	0.0304	15	1161	76	-0.18	0.024	1000	-1000	-0.059	-1000
IL2 signaling events mediated by STAT5	0.0304	15	347	22	-0.068	0.039	1000	-1000	-0.05	-1000
Insulin Pathway	0.0304	15	1137	74	-0.085	0.035	1000	-1000	-0.088	-1000
Signaling events mediated by PRL	0.0304	15	522	34	-0.11	0.013	1000	-1000	-0.039	-1000
IFN-gamma pathway	0.0283	14	989	68	-0.1	0.042	1000	-1000	-0.082	-1000
Nectin adhesion pathway	0.0283	14	922	63	-0.26	0.029	1000	-1000	-0.073	-1000
IL2 signaling events mediated by PI3K	0.0283	14	820	58	-0.066	0.031	1000	-1000	-0.079	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0283	14	467	33	-0.16	0.035	1000	-1000	-0.061	-1000
Class IB PI3K non-lipid kinase events	0.0283	14	42	3	-0.003	-1000	1000	-1000	-0.013	-1000
a4b1 and a4b7 Integrin signaling	0.0263	13	68	5	-0.033	0.002	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class III	0.0263	13	556	40	-0.35	0.024	1000	-1000	-0.04	-1000
mTOR signaling pathway	0.0243	12	652	53	-0.046	0.02	1000	-1000	-0.059	-1000
BARD1 signaling events	0.0223	11	631	57	-0.036	0.051	1000	-1000	-0.066	-1000
Cellular roles of Anthrax toxin	0.0223	11	455	39	-0.087	0.019	1000	-1000	-0.031	-1000
S1P1 pathway	0.0223	11	416	36	-0.03	0.032	1000	-1000	-0.053	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0223	11	520	45	-0.087	0.039	1000	-1000	-0.087	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0223	11	818	74	-0.18	0.085	1000	-1000	-0.086	-1000
Regulation of Telomerase	0.0223	11	1129	102	-0.28	0.052	1000	-1000	-0.1	-1000
S1P3 pathway	0.0223	11	486	42	-0.18	0.049	1000	-1000	-0.045	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0202	10	898	83	-0.21	0.052	1000	-1000	-0.065	-1000
Caspase cascade in apoptosis	0.0182	9	712	74	-0.087	0.028	1000	-1000	-0.05	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0182	9	256	28	-0.18	0.03	1000	-1000	-0.062	-1000
Retinoic acid receptors-mediated signaling	0.0182	9	544	58	-0.11	0.034	1000	-1000	-0.07	-1000
Class I PI3K signaling events mediated by Akt	0.0162	8	564	68	-0.21	0.052	1000	-1000	-0.056	-1000
TRAIL signaling pathway	0.0162	8	395	48	-0.074	0.047	1000	-1000	-0.065	-1000
ceramide signaling pathway	0.0162	8	422	49	-0.087	0.031	1000	-1000	-0.048	-1000
Canonical NF-kappaB pathway	0.0142	7	296	39	-0.087	0.073	1000	-1000	-0.075	-1000
Canonical Wnt signaling pathway	0.0142	7	374	51	-0.048	0.067	1000	-1000	-0.055	-1000
Class I PI3K signaling events	0.0142	7	553	73	-0.24	0.032	1000	-1000	-0.067	-1000
Circadian rhythm pathway	0.0121	6	143	22	-0.055	0.013	1000	-1000	-0.076	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0121	6	229	37	-0.035	0.039	1000	-1000	-0.057	-1000
FoxO family signaling	0.0121	6	424	64	-0.21	0.16	1000	-1000	-0.055	-1000
S1P4 pathway	0.0121	6	158	25	-0.017	0.032	1000	-1000	-0.044	-1000
S1P5 pathway	0.0101	5	101	17	-0.017	0.022	1000	-1000	-0.044	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0101	5	717	125	-0.036	0.085	1000	-1000	-0.087	-1000
EPO signaling pathway	0.0081	4	243	55	-0.026	0.061	1000	-1000	-0.086	-1000
Signaling events mediated by HDAC Class I	0.0081	4	495	104	-0.087	0.059	1000	-1000	-0.065	-1000
Paxillin-dependent events mediated by a4b1	0.0081	4	145	36	-0.033	0.024	1000	-1000	-0.068	-1000
Atypical NF-kappaB pathway	0.0081	4	147	31	-0.042	0.047	1000	-1000	-0.042	-1000
PLK1 signaling events	0.0061	3	286	85	-0.035	0.033	1000	-1000	-0.048	-1000
HIF-2-alpha transcription factor network	0.0061	3	137	43	-0.2	0.2	1000	-1000	-0.072	-1000
Signaling mediated by p38-gamma and p38-delta	0.0061	3	53	15	0	0.031	1000	-1000	-0.025	-1000
PDGFR-beta signaling pathway	0.0061	3	367	97	-0.18	0.064	1000	-1000	-0.08	-1000
E-cadherin signaling in keratinocytes	0.0061	3	139	43	-0.005	0.052	1000	-1000	-0.058	-1000
p38 MAPK signaling pathway	0.0061	3	151	44	-0.04	0.026	1000	-1000	-0.06	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0040	2	67	23	-0.04	0.049	1000	-1000	-0.076	-1000
Signaling events mediated by HDAC Class II	0.0040	2	177	75	-0.046	0.036	1000	-1000	-0.064	-1000
PLK2 and PLK4 events	0.0040	2	6	3	0.009	0.022	1000	-1000	-0.019	-1000
Aurora A signaling	0.0040	2	168	60	-0.05	0.038	1000	-1000	-0.058	-1000
Arf6 downstream pathway	0.0040	2	122	43	-0.17	0.091	1000	-1000	-0.038	-1000
E-cadherin signaling in the nascent adherens junction	0.0020	1	118	76	-0.17	0.073	1000	-1000	-0.084	-1000
Arf6 trafficking events	0.0020	1	82	71	-0.023	0.046	1000	-1000	-0.067	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.057	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.036	-1000
Arf1 pathway	0.0000	0	39	54	-0.006	0.035	1000	-1000	-0.045	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.062	-1000
Total	NA	4150	228004	7203	-29	-990	131000	-131000	-8.6	-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	-0.42	0.31	-9999	-0.61	346	346
EFNA5	-0.11	0.3	-9999	-0.81	76	76
FYN	-0.38	0.3	-9999	-0.55	346	346
neuron projection morphogenesis	-0.42	0.31	-9999	-0.61	346	346
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.43	0.31	-9999	-0.61	346	346
EPHA5	-0.52	0.4	-9999	-0.81	315	315

×

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	-0.22	0.22	-10000	0	-0.4	289	289
CRKL	-0.22	0.24	-10000	0	-0.42	282	282
HRAS	-0.19	0.21	-10000	0	-0.5	48	48
mol:PIP3	-0.22	0.22	-10000	0	-0.41	282	282
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.012	0.037	-10000	0	-0.81	1	1
GAB1	-0.24	0.25	-10000	0	-0.45	282	282
FOXO3	-0.2	0.22	-10000	0	-0.38	282	282
AKT1	-0.22	0.23	-10000	0	-0.42	282	282
BAD	-0.2	0.22	-10000	0	-0.38	282	282
megakaryocyte differentiation	-0.25	0.24	-10000	0	-0.45	290	290
GSK3B	-0.2	0.22	-10000	0	-0.38	282	282
RAF1	-0.15	0.18	-10000	0	-0.44	28	28
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.24	0.25	-10000	0	-0.45	282	282
STAT1	-0.6	0.58	-10000	0	-1.1	284	284
HRAS/SPRED1	-0.18	0.14	-10000	0	-0.44	30	30
cell proliferation	-0.24	0.26	-10000	0	-0.45	285	285
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.24	0.25	-10000	0	-0.45	282	282
HRAS/SPRED2	-0.18	0.14	-10000	0	-0.4	43	43
LYN/TEC/p62DOK	-0.24	0.21	-10000	0	-0.41	282	282
MAPK3	-0.097	0.13	-10000	0	-0.31	22	22
STAP1	-0.26	0.25	-10000	0	-0.47	282	282
GRAP2	-0.045	0.21	-10000	0	-0.75	38	38
JAK2	-0.52	0.45	-10000	0	-0.9	284	284
STAT1 (dimer)	-0.58	0.57	-10000	0	-1.1	284	284
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.25	0.21	-10000	0	-0.42	285	285
actin filament polymerization	-0.24	0.24	-10000	0	-0.44	282	282
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.35	0.34	-10000	0	-0.64	282	282
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.21	0.19	-10000	0	-0.37	282	282
PI3K	-0.22	0.24	-10000	0	-0.42	283	283
PTEN	0.012	0.037	-10000	0	-0.81	1	1
SCF/KIT/EPO/EPOR	-0.74	0.71	-10000	0	-1.4	282	282
MAPK8	-0.25	0.26	-10000	0	-0.46	285	285
STAT3 (dimer)	-0.23	0.24	-10000	0	-0.44	282	282
positive regulation of transcription	-0.077	0.11	-10000	0	-0.25	22	22
mol:GDP	-0.23	0.19	-10000	0	-0.47	79	79
PIK3C2B	-0.24	0.25	-10000	0	-0.45	282	282
CBL/CRKL	-0.2	0.22	-10000	0	-0.39	282	282
FER	-0.24	0.25	-10000	0	-0.45	283	283
SH2B3	-0.24	0.25	-10000	0	-0.45	282	282
PDPK1	-0.2	0.21	-10000	0	-0.37	283	283
SNAI2	-0.25	0.26	-10000	0	-0.46	284	284
positive regulation of cell proliferation	-0.42	0.42	-10000	0	-0.77	284	284
KITLG	-0.005	0.11	-10000	0	-0.85	8	8
cell motility	-0.42	0.42	-10000	0	-0.77	284	284
PTPN6	0.021	0.018	-10000	0	-10000	0	0
EPOR	-0.14	0.18	-10000	0	-0.56	8	8
STAT5A (dimer)	-0.34	0.34	-10000	0	-0.63	284	284
SOCS1	0.008	0.049	-10000	0	-0.39	6	6
cell migration	0.24	0.25	0.45	285	-10000	0	285
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.005	0.041	-10000	0	-0.32	7	7
VAV1	-0.015	0.1	-10000	0	-0.35	39	39
GRB10	-0.24	0.25	-10000	0	-0.45	282	282
PTPN11	0.02	0.038	-10000	0	-0.8	1	1
SCF/KIT	-0.26	0.26	-10000	0	-0.48	282	282
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.11	0.14	-10000	0	-0.34	25	25
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.8	0.74	-10000	0	-1.4	282	282
MAP2K2	-0.11	0.14	-10000	0	-0.35	22	22
SHC/Grb2/SOS1	-0.24	0.21	-10000	0	-0.41	282	282
STAT5A	-0.35	0.36	-10000	0	-0.65	284	284
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.24	0.25	-10000	0	-0.45	284	284
SHC/GRAP2	-0.044	0.16	-10000	0	-0.62	33	33
PTPRO	-0.26	0.25	-10000	0	-0.46	290	290
SH2B2	-0.24	0.25	-10000	0	-0.45	282	282
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.25	0.25	-10000	0	-0.46	285	285
CREBBP	0.017	0.02	-10000	0	-10000	0	0
BCL2	-0.22	0.42	-10000	0	-1.6	36	36

×

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	-0.088	0.068	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.25	0.2	-9999	-0.5	122	122
JUN	-0.32	0.31	-9999	-0.66	180	180
HRAS	0.012	0.021	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.38	0.32	-9999	-0.6	304	304
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	-0.38	0.32	-9999	-0.6	304	304
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.29	0.25	-9999	-0.51	280	280
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.34	0.29	-9999	-0.54	304	304
GRB7	-0.04	0.12	-9999	-0.31	82	82
RET51/GFRalpha1/GDNF	-0.38	0.32	-9999	-0.6	304	304
MAPKKK cascade	-0.3	0.26	-9999	-0.48	304	304
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.34	0.31	-9999	-0.58	293	293
lamellipodium assembly	-0.24	0.18	-9999	-0.38	281	281
RET51/GFRalpha1/GDNF/SHC	-0.38	0.32	-9999	-0.6	304	304
PIK3CA	0.008	0.064	-9999	-0.81	3	3
RET9/GFRalpha1/GDNF/SHC	-0.29	0.25	-9999	-0.5	280	280
RET9/GFRalpha1/GDNF/Shank3	-0.29	0.25	-9999	-0.5	280	280
MAPK3	-0.31	0.29	-9999	-0.51	304	304
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.12	0.3	-9999	-0.81	79	79
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.3	0.29	-9999	-0.66	131	131
DOK5	-0.099	0.28	-9999	-0.81	67	67
GFRA1	-0.46	0.41	-9999	-0.81	281	281
MAPK8	-0.23	0.24	-9999	-0.39	307	307
HRAS/GTP	-0.35	0.3	-9999	-0.56	304	304
tube development	-0.27	0.23	-9999	-0.47	280	280
MAPK1	-0.31	0.29	-9999	-0.51	304	304
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.18	0.18	-9999	-0.34	280	280
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-10000	0	0
PDLIM7	0.011	0.029	-9999	-0.31	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.43	0.38	-9999	-0.66	315	315
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.38	0.32	-9999	-0.6	304	304
RET51/GFRalpha1/GDNF/Dok5	-0.44	0.38	-9999	-0.68	316	316
PRKCA	-0.018	0.16	-9999	-0.81	19	19
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
CREB1	-0.24	0.24	-9999	-0.43	280	280
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.18	0.18	-9999	-0.34	280	280
RET51/GFRalpha1/GDNF/Grb7	-0.4	0.32	-9999	-0.63	304	304
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.16	0.31	-9999	-0.63	135	135
DOK4	0.013	0.015	-9999	-0.31	1	1
JNK cascade	-0.31	0.3	-9999	-0.64	180	180
RET9/GFRalpha1/GDNF/FRS2	-0.29	0.25	-9999	-0.5	280	280
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	280	280
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.24	0.24	-9999	-0.41	304	304
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.24	0.23	-9999	-0.41	304	304
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.28	0.31	-9999	-0.47	304	304
PI3K	-0.36	0.34	-9999	-0.62	281	281
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.27	0.23	-9999	-0.47	280	280
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.22	0.21	-9999	-0.38	280	280
RET51/GFRalpha1/GDNF/FRS2	-0.38	0.32	-9999	-0.6	304	304
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.085	0.27	-9999	-0.81	59	59
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.28	0.31	-9999	-0.47	304	304
RET51/GFRalpha1/GDNF/PKC alpha	-0.4	0.34	-9999	-0.63	305	305
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.002	0.042	-9999	-0.31	9	9
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.44	0.36	-9999	-0.67	316	316
Rac1/GTP	-0.29	0.23	-9999	-0.46	281	281
RET9/GFRalpha1/GDNF	-0.32	0.27	-9999	-0.56	280	280
GFRalpha1/GDNF	-0.36	0.31	-9999	-0.63	280	280

×

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	204	204
CDKN2C	0.026	0.036	-10000	0	-0.32	3	3
CDKN2A	-0.12	0.16	-10000	0	-0.31	204	204
CCND2	0.068	0.071	0.17	138	-10000	0	138
RB1	-0.067	0.071	-10000	0	-0.17	138	138
CDK4	0.068	0.07	0.17	139	-10000	0	139
CDK6	0.071	0.076	0.18	138	-0.18	2	140
G1/S progression	0.059	0.078	0.17	138	-10000	0	138

×

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	0.015	-9999	-10000	0	0
VLDLR	-0.02	0.16	-9999	-0.81	20	20
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	0.032	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.41	0.26	-9999	-0.56	366	366
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.067	-9999	-0.46	11	11
AKT1	-0.23	0.17	-9999	-0.33	367	367
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	-0.38	0.24	-9999	-0.52	364	364
LRPAP1/LRP8	-0.025	0.12	-9999	-0.62	20	20
RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	364	364
DAB1/alpha3/beta1 Integrin	-0.34	0.23	-9999	-0.45	370	370
long-term memory	-0.36	0.24	-9999	-0.48	366	366
DAB1/LIS1	-0.35	0.23	-9999	-0.47	370	370
DAB1/CRLK/C3G	-0.34	0.22	-9999	-0.45	370	370
PIK3CA	0.008	0.064	-9999	-0.81	3	3
DAB1/NCK2	-0.35	0.24	-9999	-0.47	370	370
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.022	0.16	-9999	-0.63	27	27
CDK5R1	0.011	0.025	-9999	-0.31	3	3
RELN	-0.59	0.37	-9999	-0.81	360	360
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.41	0.26	-9999	-0.56	364	364
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.37	0.25	-9999	-0.5	366	366
MAPK8	-0.005	0.12	-9999	-0.81	11	11
RELN/VLDLR/DAB1	-0.38	0.24	-9999	-0.52	366	366
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.36	0.26	-9999	-0.49	370	370
RELN/LRP8	-0.41	0.26	-9999	-0.56	364	364
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	364	364
PI3K	-0.004	0.048	-9999	-0.62	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.02	-9999	-10000	0	0
RAP1A	-0.3	0.23	-9999	-0.82	27	27
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	0.015	-9999	-0.31	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.14	-9999	-0.52	23	23
neuron adhesion	-0.28	0.22	-9999	-0.73	31	31
LRP8	-0.02	0.16	-9999	-0.81	20	20
GSK3B	-0.21	0.16	-9999	-0.61	16	16
RELN/VLDLR/DAB1/Fyn	-0.36	0.23	-9999	-0.49	366	366
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.35	367	367
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.033	0.087	-9999	-0.56	5	5
neuron migration	-0.29	0.22	-9999	-0.41	361	361
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.14	-9999	-0.52	23	23
RELN/VLDLR	-0.4	0.26	-9999	-0.53	370	370

×

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	-0.04	0.16	-10000	0	-0.52	35	35
NFATC2	-0.24	0.38	-10000	0	-0.81	130	130
NFATC3	-0.084	0.13	-10000	0	-10000	0	0
CD40LG	-0.74	0.57	-10000	0	-1.2	296	296
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	-0.54	0.53	-10000	0	-1.2	147	147
JUNB	0.003	0.091	-10000	0	-0.81	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	-0.24	0.44	-10000	0	-0.86	141	141
Jun/NFAT1-c-4/p21SNFT	-0.66	0.6	-10000	0	-1.2	258	258
AP-1/NFAT1-c-4	-0.9	0.78	-10000	0	-1.4	286	286
IKZF1	-0.18	0.34	-10000	0	-0.72	110	110
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.87	110	110
AP-1/NFAT1	-0.42	0.48	-10000	0	-0.9	217	217
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.85	-10000	0	-1.6	236	236
EGR3	-0.56	0.73	-10000	0	-1.2	219	219
NFAT1/FOXP3	-0.22	0.34	-10000	0	-0.69	132	132
EGR1	-0.17	0.34	-10000	0	-0.82	107	107
JUN	-0.19	0.34	-10000	0	-0.82	112	112
EGR4	-0.036	0.18	-10000	0	-0.72	31	31
mol:Ca2+	0.016	0.01	-10000	0	-10000	0	0
GBP3	-0.17	0.32	-10000	0	-0.69	107	107
FOSL1	-0.032	0.12	-10000	0	-0.32	68	68
NFAT1-c-4/MAF/IRF4	-0.57	0.56	-10000	0	-1	254	254
DGKA	-0.16	0.3	-10000	0	-0.67	101	101
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.56	0.56	-10000	0	-1	254	254
CTLA4	-0.24	0.39	-10000	0	-0.84	116	116
NFAT1-c-4 (dimer)/EGR1	-0.65	0.66	-10000	0	-1.2	255	255
NFAT1-c-4 (dimer)/EGR4	-0.58	0.56	-10000	0	-1	257	257
FOS	-0.21	0.36	-10000	0	-0.82	127	127
IFNG	-0.43	0.54	-10000	0	-1.2	142	142
T cell activation	-0.44	0.42	-10000	0	-0.94	172	172
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	0.42	0.75	234	-10000	0	234
TNF	-0.6	0.57	-10000	0	-1.1	270	270
FASLG	-0.75	0.78	-10000	0	-1.4	251	251
TBX21	-0.039	0.18	-10000	0	-0.68	33	33
BATF3	-0.005	0.081	-10000	0	-0.33	27	27
PRKCQ	0.003	0.092	-10000	0	-0.81	6	6
PTPN1	-0.16	0.3	-10000	0	-0.66	101	101
NFAT1-c-4/ICER1	-0.55	0.55	-10000	0	-1	252	252
GATA3	-0.029	0.18	-10000	0	-0.78	27	27
T-helper 1 cell differentiation	-0.41	0.52	-10000	0	-1.1	144	144
IL2RA	-0.49	0.46	-10000	0	-1	158	158
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.3	-10000	0	-0.66	104	104
E2F1	-0.078	0.15	-10000	0	-10000	0	0
PPARG	-0.002	0.1	-10000	0	-0.6	12	12
SLC3A2	-0.16	0.3	-10000	0	-0.67	98	98
IRF4	-0.1	0.24	-10000	0	-0.47	116	116
PTGS2	-0.71	0.56	-10000	0	-1.1	282	282
CSF2	-0.78	0.53	-10000	0	-1.2	299	299
JunB/Fra1/NFAT1-c-4	-0.54	0.53	-10000	0	-1	250	250
IL4	-0.33	0.37	-10000	0	-0.94	105	105
IL5	-0.7	0.54	-10000	0	-1.1	283	283
IL2	-0.45	0.44	-10000	0	-0.97	171	171
IL3	-0.097	0.062	-10000	0	-10000	0	0
RNF128	0.049	0.041	-10000	0	-0.87	1	1
NFATC1	-0.37	0.42	-10000	0	-0.75	234	234
CDK4	0.22	0.24	0.59	69	-10000	0	69
PTPRK	-0.16	0.3	-10000	0	-0.74	74	74
IL8	-0.72	0.54	-10000	0	-1.1	290	290
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.27	0.28	-9999	-0.46	307	307
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.003	0.055	-9999	-0.31	15	15
WNT4	-0.26	0.39	-9999	-0.8	164	164
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.004	0.12	-9999	-0.77	11	11
WNT11	-0.41	0.41	-9999	-0.81	253	253

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.51	0.54	-9999	-1.1	210	210
PCK1	-0.34	0.49	-9999	-1.3	77	77
HNF4A	-0.66	0.65	-9999	-1.3	246	246
KCNJ11	-0.48	0.54	-9999	-1	201	201
AKT1	-0.042	0.12	-9999	-0.37	18	18
response to starvation	-0.017	0.033	-9999	-10000	0	0
DLK1	-0.49	0.53	-9999	-1.1	187	187
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.51	0.54	-9999	-1	220	220
TAT	-0.2	0.22	-9999	-0.62	22	22
CEBPB	0.013	0.005	-9999	-10000	0	0
CEBPA	0.005	0.083	-9999	-0.81	5	5
TTR	-0.19	0.22	-9999	-0.74	33	33
PKLR	-0.52	0.54	-9999	-1	220	220
APOA1	-0.91	0.89	-9999	-1.7	254	254
CPT1C	-0.53	0.54	-9999	-1	227	227
ALAS1	-0.16	0.21	-9999	-10000	0	0
TFRC	-0.26	0.3	-9999	-0.7	64	64
FOXF1	-0.007	0.075	-9999	-0.72	5	5
NF1	0.021	0.001	-9999	-10000	0	0
HNF1A (dimer)	0.015	0.007	-9999	-10000	0	0
CPT1A	-0.51	0.54	-9999	-1	220	220
HMGCS1	-0.51	0.54	-9999	-1	220	220
NR3C1	0.019	0.017	-9999	-10000	0	0
CPT1B	-0.51	0.54	-9999	-1	213	213
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.66	0.7	-9999	-1.3	240	240
CREB1	0	0.053	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.56	12	12
PDX1	-0.18	0.21	-9999	-0.6	1	1
UCP2	-0.51	0.54	-9999	-1	221	221
ALDOB	-0.48	0.54	-9999	-1	202	202
AFP	-0.045	0.11	-9999	-0.48	10	10
BDH1	-0.51	0.54	-9999	-1	214	214
HADH	-0.48	0.53	-9999	-1	202	202
F2	-0.62	0.63	-9999	-1.3	212	212
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.006	0.09	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.7	2	2
INS	-0.013	0.066	-9999	-0.82	3	3
FOXA1	-0.053	0.14	-9999	-0.34	79	79
FOXA3	-0.072	0.17	-9999	-0.5	35	35
FOXA2	-0.55	0.6	-9999	-1.1	224	224
ABCC8	-0.78	0.74	-9999	-1.4	274	274
ALB	-0.094	0.31	-9999	-1.3	29	29

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.25	0.38	-9999	-0.83	151	151
PDGF/PDGFRA/CRKL	-0.19	0.29	-9999	-0.62	151	151
positive regulation of JUN kinase activity	-0.15	0.22	-9999	-0.48	151	151
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.2	0.29	-9999	-0.63	151	151
AP1	-0.49	0.62	-9999	-1.4	134	134
mol:IP3	-0.19	0.3	-9999	-0.64	151	151
PLCG1	-0.19	0.3	-9999	-0.65	151	151
PDGF/PDGFRA/alphaV Integrin	-0.19	0.29	-9999	-0.62	152	152
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.3	-9999	-0.64	151	151
CAV3	-0.001	0.028	-9999	-0.31	4	4
CAV1	-0.008	0.13	-9999	-0.81	13	13
SHC/Grb2/SOS1	-0.15	0.22	-9999	-0.48	151	151
PDGF/PDGFRA/Shf	-0.19	0.29	-9999	-0.62	151	151
FOS	-0.44	0.6	-9999	-1.4	134	134
JUN	-0.17	0.28	-9999	-0.7	112	112
oligodendrocyte development	-0.19	0.29	-9999	-0.62	152	152
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.19	0.3	-9999	-0.64	151	151
PDGF/PDGFRA	-0.25	0.38	-9999	-0.83	151	151
actin cytoskeleton reorganization	-0.19	0.29	-9999	-0.62	151	151
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.17	0.25	-9999	-0.53	154	154
PDGF/PDGFRA/Crk/C3G	-0.16	0.24	-9999	-0.53	151	151
JAK1	-0.18	0.3	-9999	-0.62	151	151
ELK1/SRF	-0.12	0.24	-9999	-0.48	151	151
SHB	0.013	0	-9999	-10000	0	0
SHF	0.013	0.015	-9999	-0.31	1	1
CSNK2A1	0.027	0.027	-9999	-10000	0	0
GO:0007205	-0.2	0.31	-9999	-0.66	151	151
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.15	0.22	-9999	-0.48	151	151
PDGF/PDGFRA/SHB	-0.19	0.29	-9999	-0.62	151	151
PDGF/PDGFRA/Caveolin-1	-0.2	0.31	-9999	-0.66	154	154
ITGAV	0.01	0.053	-9999	-0.81	2	2
ELK1	-0.18	0.28	-9999	-0.59	151	151
PIK3CA	0.008	0.064	-9999	-0.81	3	3
PDGF/PDGFRA/Crk	-0.19	0.29	-9999	-0.62	151	151
JAK-STAT cascade	-0.18	0.29	-9999	-0.62	151	151
cell proliferation	-0.19	0.29	-9999	-0.62	151	151

×

Noncanonical Wnt 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
NFATC2	-0.13	0.31	-9999	-0.81	86	86
GNB1/GNG2	-0.26	0.24	-9999	-0.61	119	119
mol:DAG	-0.21	0.24	-9999	-0.55	117	117
PLCG1	-0.22	0.24	-9999	-0.57	117	117
YES1	-0.25	0.26	-9999	-0.62	126	126
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.22	0.24	-9999	-0.57	117	117
MAP3K7	-0.17	0.2	-9999	-0.45	117	117
mol:Ca2+	-0.2	0.23	-9999	-0.53	117	117
mol:IP3	-0.21	0.24	-9999	-0.55	117	117
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	131	131
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.27	0.28	-9999	-0.46	307	307
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.25	0.26	-9999	-0.62	126	126
GO:0007205	-0.2	0.23	-9999	-0.54	117	117
WNT6	0.003	0.055	-9999	-0.31	15	15
WNT4	-0.26	0.39	-9999	-0.8	164	164
NFAT1/CK1 alpha	-0.3	0.25	-9999	-0.62	150	150
GNG2	0.012	0.037	-9999	-0.81	1	1
WNT5A	-0.004	0.12	-9999	-0.77	11	11
WNT11	-0.41	0.41	-9999	-0.81	253	253
CDC42	-0.23	0.25	-9999	-0.58	126	126

×

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	-0.6	0.44	-10000	0	-1.1	166	166
STAT6 (cleaved dimer)	-0.65	0.44	-10000	0	-1	258	258
IGHG1	-0.21	0.14	-10000	0	-0.36	44	44
IGHG3	-0.59	0.42	-10000	0	-0.97	223	223
AKT1	-0.32	0.26	-10000	0	-0.71	79	79
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.25	-10000	0	-0.74	58	58
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.36	0.28	-10000	0	-0.75	104	104
THY1	-0.6	0.44	-10000	0	-1.1	138	138
MYB	-0.009	0.13	-10000	0	-0.64	17	17
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.42	0.31	-10000	0	-0.73	169	169
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.77	58	58
SP1	0.02	0.006	-10000	0	-10000	0	0
INPP5D	-0.003	0.071	-10000	0	-0.31	25	25
SOCS5	0.03	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.63	0.44	-10000	0	-1	229	229
SOCS1	-0.41	0.29	-10000	0	-0.72	138	138
SOCS3	-0.37	0.34	-10000	0	-0.97	73	73
FCER2	-0.63	0.47	-10000	0	-1	213	213
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.67	0.47	-10000	0	-1.1	196	196
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.68	46	46
T cell proliferation	-0.61	0.46	-10000	0	-1.1	182	182
IL4R/JAK1	-0.6	0.44	-10000	0	-1.1	164	164
EGR2	-0.96	0.72	-10000	0	-1.6	248	248
JAK2	-0.02	0.058	-10000	0	-0.85	2	2
JAK3	-0.066	0.14	-10000	0	-0.31	125	125
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.008	-10000	0	-10000	0	0
COL1A2	-0.2	0.17	-10000	0	-0.61	19	19
CCL26	-0.62	0.45	-10000	0	-1.1	169	169
IL4R	-0.64	0.46	-10000	0	-1.2	164	164
PTPN6	0.029	0.009	-10000	0	-10000	0	0
IL13RA2	-0.71	0.56	-10000	0	-1.3	194	194
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.36	0.5	-10000	0	-1.2	106	106
ARG1	-0.15	0.11	-10000	0	-10000	0	0
CBL	-0.39	0.29	-10000	0	-0.73	139	139
GTF3A	0.016	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
IL13RA1/JAK2	-0.026	0.052	-10000	0	-0.66	2	2
IRF4/BCL6	-0.32	0.46	-10000	0	-1.1	101	101
CD40LG	-0.13	0.31	-10000	0	-0.8	87	87
MAPK14	-0.39	0.31	-10000	0	-0.77	130	130
mitosis	-0.31	0.24	-10000	0	-0.66	81	81
STAT6	-0.68	0.51	-10000	0	-1.2	204	204
SPI1	0	0.074	-10000	0	-0.31	27	27
RPS6KB1	-0.29	0.23	-10000	0	-0.67	66	66
STAT6 (dimer)	-0.68	0.51	-10000	0	-1.2	204	204
STAT6 (dimer)/PARP14	-0.64	0.47	-10000	0	-1.1	198	198
mast cell activation	0.016	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.32	0.27	-10000	0	-0.75	79	79
FRAP1	-0.32	0.26	-10000	0	-0.71	80	80
LTA	-0.62	0.45	-10000	0	-1.1	175	175
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.67	0.49	1.1	207	-10000	0	207
CCL11	-0.59	0.43	-10000	0	-1.1	154	154
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.73	81	81
IL2RG	-0.045	0.19	-10000	0	-0.52	57	57
IL10	-0.62	0.47	-10000	0	-1.1	174	174
IRS1	-0.085	0.27	-10000	0	-0.81	59	59
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.094	-10000	0	-10000	0	0
IL5	-0.61	0.44	-10000	0	-1.1	173	173
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.49	0.33	-10000	0	-0.84	170	170
COL1A1	-0.26	0.23	-10000	0	-0.67	48	48
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.6	0.45	-10000	0	-1.2	125	125
IL2R gamma/JAK3	-0.081	0.18	-10000	0	-0.5	57	57
TFF3	-1.3	0.61	-10000	0	-1.6	402	402
ALOX15	-0.6	0.44	-10000	0	-1.1	165	165
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.52	0.36	-10000	0	-0.87	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	-0.31	0.25	-10000	0	-0.72	64	64
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.71	80	80
PI3K	-0.34	0.28	-10000	0	-0.77	76	76
DOK2	-0.001	0.078	-10000	0	-0.36	19	19
ETS1	0.03	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.25	0.21	-10000	0	-0.67	45	45
ITGB3	-0.62	0.47	-10000	0	-1.2	157	157
PIGR	-0.65	0.5	-10000	0	-1.2	151	151
IGHE	0.052	0.035	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.66	45	45
BCL6	0.012	0.037	-10000	0	-0.81	1	1
OPRM1	-0.61	0.44	-10000	0	-1.1	166	166
RETNLB	-0.61	0.44	-10000	0	-1.1	167	167
SELP	-0.61	0.45	-10000	0	-1.1	165	165
AICDA	-0.59	0.42	-10000	0	-1.1	163	163

×

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	-0.68	35	35
IHH	-0.2	0.37	-10000	0	-0.83	123	123
SHH Np/Cholesterol/GAS1	-0.1	0.2	-10000	0	-0.51	96	96
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.1	0.2	0.51	96	-10000	0	96
SMO/beta Arrestin2	-0.095	0.24	-10000	0	-0.48	126	126
SMO	-0.11	0.25	-10000	0	-0.51	127	127
AKT1	-0.027	0.12	-10000	0	-0.54	3	3
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	0	0.1	-10000	0	-0.81	8	8
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.1	0.25	-10000	0	-0.5	127	127
STIL	-0.077	0.2	-10000	0	-0.59	18	18
DHH N/PTCH2	-0.11	0.24	-10000	0	-0.64	82	82
DHH N/PTCH1	-0.099	0.22	-10000	0	-0.45	130	130
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
DHH	0.007	0.074	-10000	0	-0.81	4	4
PTHLH	-0.16	0.36	-10000	0	-1.2	35	35
determination of left/right symmetry	-0.1	0.25	-10000	0	-0.5	127	127
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.15	0.36	-10000	0	-1.1	35	35
IHH N/Hhip	-0.38	0.4	-10000	0	-0.73	263	263
DHH N/Hhip	-0.25	0.31	-10000	0	-0.63	195	195
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.1	0.25	-10000	0	-0.5	127	127
pancreas development	-0.31	0.4	-10000	0	-0.81	195	195
HHAT	0.012	0.037	-10000	0	-0.81	1	1
PI3K	-0.004	0.048	-10000	0	-0.62	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.15	0.33	-10000	0	-0.81	95	95
somite specification	-0.1	0.25	-10000	0	-0.5	127	127
SHH Np/Cholesterol/PTCH1	-0.087	0.2	-10000	0	-0.42	86	86
SHH Np/Cholesterol/PTCH2	-0.087	0.19	-10000	0	-0.51	81	81
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.51	134	134
SHH	0.007	0.049	-10000	0	-0.62	1	1
catabolic process	-0.11	0.25	-10000	0	-0.5	128	128
SMO/Vitamin D3	-0.091	0.22	-10000	0	-0.44	127	127
SHH Np/Cholesterol/Hhip	-0.2	0.24	-10000	0	-0.5	195	195
LRP2	-0.21	0.37	-10000	0	-0.81	133	133
receptor-mediated endocytosis	-0.2	0.23	-10000	0	-0.71	49	49
SHH Np/Cholesterol/BOC	-0.014	0.073	-10000	0	-0.52	9	9
SHH Np/Cholesterol/CDO	-0.15	0.23	-10000	0	-0.51	146	146
mesenchymal cell differentiation	0.2	0.24	0.5	195	-10000	0	195
mol:Vitamin D3	-0.086	0.2	-10000	0	-0.42	86	86
IHH N/PTCH2	-0.23	0.34	-10000	0	-0.66	181	181
CDON	-0.23	0.38	-10000	0	-0.81	145	145
IHH N/PTCH1	-0.12	0.25	-10000	0	-0.51	128	128
Megalin/LRPAP1	-0.17	0.28	-10000	0	-0.62	133	133
PTCH2	-0.12	0.3	-10000	0	-0.81	80	80
SHH Np/Cholesterol	-0.006	0.035	-10000	0	-0.5	1	1
PTCH1	-0.11	0.25	-10000	0	-0.5	128	128
HHIP	-0.31	0.4	-10000	0	-0.81	195	195

×

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	-0.5	210	210
regulation of S phase of mitotic cell cycle	-0.13	0.18	-10000	0	-0.34	211	211
GNAO1	-0.017	0.15	-10000	0	-0.69	21	21
HRAS	0.012	0.021	-10000	0	-0.31	2	2
SHBG/T-DHT	-0.008	0.07	-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	-0.16	0.23	-10000	0	-0.43	209	209
T-DHT/AR	-0.27	0.31	-10000	0	-0.64	209	209
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	127	127
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.037	-10000	0	-0.82	1	1
mol:GDP	-0.26	0.3	-10000	0	-0.61	210	210
cell proliferation	-0.2	0.28	-10000	0	-0.68	78	78
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
FOS	-0.24	0.39	-10000	0	-0.89	127	127
mol:Ca2+	-0.027	0.03	-10000	0	-0.071	92	92
MAPK3	-0.18	0.26	-10000	0	-0.6	84	84
MAPK1	-0.082	0.13	-10000	0	-0.31	75	75
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	127	127
cAMP biosynthetic process	0.016	0.074	-10000	0	-0.52	8	8
GNG2	0.012	0.037	-10000	0	-0.81	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	127	127
HRAS/GTP	-0.2	0.23	-10000	0	-0.46	209	209
actin cytoskeleton reorganization	-0.003	0.034	-10000	0	-0.44	3	3
SRC	0.012	0.015	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	127	127
PI3K	-0.003	0.042	-10000	0	-0.55	3	3
apoptosis	0.16	0.25	0.52	127	-10000	0	127
T-DHT/AR/PELP1	-0.23	0.27	-10000	0	-0.55	209	209
HRAS/GDP	-0.25	0.29	-10000	0	-0.58	210	210
CREB1	-0.17	0.27	-10000	0	-0.57	127	127
RAC1-CDC42/GTP	-0.003	0.035	-10000	0	-0.45	3	3
AR	-0.34	0.41	-10000	0	-0.82	209	209
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.17	0.24	-10000	0	-0.45	209	209
RAC1-CDC42/GDP	-0.23	0.27	-10000	0	-0.55	209	209
T-DHT/AR/PELP1/Src	-0.21	0.25	-10000	0	-0.5	209	209
MAP2K2	-0.16	0.23	-10000	0	-0.43	209	209
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.18	-10000	0	-0.34	211	211
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	0	0.1	-10000	0	-0.81	8	8
Gi family/GNB1/GNG2/GDP	-0.02	0.12	-10000	0	-0.53	17	17
mol:T-DHT	0	0.001	0.001	75	-0.003	50	125
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.042	-10000	0	-0.63	2	2
Gi family/GTP	-0.095	0.12	-10000	0	-0.46	18	18
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	-0.02	0.16	-9999	-0.81	20	20
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.41	0.26	-9999	-0.56	364	364
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	-0.36	0.25	-9999	-0.51	364	364
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	-0.092	0.28	-9999	-0.81	63	63
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	-0.025	0.12	-9999	-0.62	20	20
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.011	0.025	-9999	-0.31	3	3
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	0.004	0.021	-9999	-0.31	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.42	0.26	-9999	-0.56	366	366
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.27	0.2	-9999	-0.68	18	18
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.31	0.22	-9999	-0.44	364	364
RELN	-0.59	0.37	-9999	-0.81	360	360
PAFAH/LIS1	-0.044	0.19	-9999	-0.54	63	63
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.22	0.14	-9999	-0.54	16	16
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.24	0.18	-9999	-0.34	371	371
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.29	0.22	-9999	-0.42	364	364
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	0.029	-9999	-0.31	4	4
PAFAH1B2	-0.002	0.11	-9999	-0.81	9	9
MAP1B/LIS1/Dynein heavy chain	0.027	0.003	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.27	0.17	-9999	-0.69	16	16
LRP8	-0.02	0.16	-9999	-0.81	20	20
NDEL1/Katanin 60	-0.27	0.2	-9999	-0.68	18	18
P39/CDK5	-0.32	0.23	-9999	-0.44	364	364
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.34	0.24	-9999	-0.47	364	364
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	0.22	-9999	-0.48	366	366
RELN/VLDLR	-0.4	0.26	-9999	-0.53	370	370
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	0.079	-9999	-0.56	9	9
NFATC2	-0.1	0.22	-9999	-0.57	86	86
NFATC3	0	0.027	-9999	-10000	0	0
CD40LG	-0.44	0.42	-9999	-0.88	204	204
PTGS2	-0.41	0.4	-9999	-0.84	188	188
JUNB	0.003	0.091	-9999	-0.81	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	-0.82	112	112
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	-0.032	0.12	-9999	-0.32	68	68
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.58	178	178
FOS	-0.21	0.36	-9999	-0.82	127	127
IFNG	-0.44	0.41	-9999	-0.86	201	201
AP-1/NFAT1-c-4	-0.52	0.52	-9999	-0.97	229	229
FASLG	-0.42	0.39	-9999	-0.84	194	194
NFAT1-c-4/ICER1	-0.12	0.2	-9999	-0.5	94	94
IL2RA	-0.41	0.39	-9999	-0.83	185	185
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.47	0.36	-9999	-0.76	268	268
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.5	96	96
IL4	-0.39	0.36	-9999	-0.8	183	183
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	-0.005	0.081	-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	0.17	0.3	0.68	121	-10000	0	121
KIRREL	-0.073	0.24	-10000	0	-0.84	44	44
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.17	0.3	-10000	0	-0.69	121	121
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	121	121
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.077	0.2	-10000	0	-0.41	121	121
FYN	-0.11	0.24	-10000	0	-0.51	121	121
mol:Ca2+	-0.13	0.24	-10000	0	-0.53	121	121
mol:DAG	-0.13	0.24	-10000	0	-0.53	121	121
NPHS2	-0.017	0.052	-10000	0	-0.89	1	1
mol:IP3	-0.13	0.24	-10000	0	-0.53	121	121
regulation of endocytosis	-0.12	0.21	-10000	0	-0.47	121	121
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.54	121	121
establishment of cell polarity	-0.17	0.3	-10000	0	-0.68	121	121
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.22	-10000	0	-0.49	121	121
Nephrin/NEPH1/beta Arrestin2	-0.1	0.23	-10000	0	-0.48	121	121
NPHS1	-0.15	0.32	-10000	0	-0.82	92	92
Nephrin/NEPH1/podocin	-0.12	0.23	-10000	0	-0.51	121	121
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	121	121
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.13	0.24	-10000	0	-0.54	121	121
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.11	0.25	-10000	0	-0.51	125	125
cytoskeleton organization	-0.1	0.26	-10000	0	-0.53	121	121
Nephrin/NEPH1	-0.13	0.24	-10000	0	-0.52	121	121
Nephrin/NEPH1/ZO-1	-0.14	0.26	-10000	0	-0.57	121	121

×

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	0.025	-10000	0	-0.54	1	1
fibroblast growth factor receptor signaling pathway	-0.001	0.025	-10000	0	-0.54	1	1
LAMA1	-0.048	0.22	-10000	0	-0.8	37	37
PRNP	0.012	0.037	-10000	0	-0.81	1	1
GPC1/SLIT2	-0.095	0.22	-10000	0	-0.62	74	74
SMAD2	0.028	0.048	-10000	0	-0.49	3	3
GPC1/PrPc/Cu2+	-0.001	0.026	-10000	0	-0.55	1	1
GPC1/Laminin alpha1	-0.046	0.16	-10000	0	-0.62	36	36
TDGF1	-0.34	0.41	-10000	0	-0.81	209	209
CRIPTO/GPC1	-0.26	0.31	-10000	0	-0.62	209	209
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	209	209
FLT1	0.012	0.037	-10000	0	-0.81	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.007	0.048	-10000	0	-0.54	3	3
SERPINC1	0.006	0.046	-10000	0	-0.31	10	10
FYN	-0.21	0.28	-10000	0	-0.54	209	209
FGR	-0.21	0.28	-10000	0	-0.54	209	209
positive regulation of MAPKKK cascade	-0.28	0.31	-10000	0	-0.61	211	211
SLIT2	-0.11	0.3	-10000	0	-0.79	77	77
GPC1/NRG	-0.058	0.18	-10000	0	-0.62	45	45
NRG1	-0.063	0.24	-10000	0	-0.79	47	47
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.005	0.058	-10000	0	-0.7	3	3
LYN	-0.21	0.28	-10000	0	-0.54	209	209
mol:Spermine	0.012	0.01	-10000	0	-10000	0	0
cell growth	-0.001	0.025	-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	-0.54	209	209
TGFBR1	0.006	0.05	-10000	0	-0.31	12	12
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.24	0.36	-10000	0	-0.68	185	185
GPC1	0.013	0.015	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.006	0.05	-10000	0	-0.31	12	12
VEGFA	0.008	0.064	-10000	0	-0.81	3	3
BLK	-0.38	0.37	-10000	0	-0.66	284	284
HCK	-0.22	0.28	-10000	0	-0.55	209	209
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.012	0.037	-10000	0	-0.81	1	1
VEGFR1 homodimer	0.012	0.037	-10000	0	-0.81	1	1
TGFBR2	0.008	0.064	-10000	0	-0.81	3	3
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.004	0.029	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.19	0.27	-10000	0	-0.62	134	134
LCK	-0.22	0.28	-10000	0	-0.54	214	214
neuron differentiation	-0.058	0.18	-10000	0	-0.62	45	45
PrPc/Cu2+	-0.001	0.028	-10000	0	-0.63	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.008	0.064	-10000	0	-0.81	3	3

×

HIF-1-alpha transcription factor network

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
PKM2	-0.19	0.42	-9999	-0.9	70	70
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.34	-9999	-0.81	112	112
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.19	0.42	-9999	-0.9	70	70
AP1	-0.28	0.45	-9999	-0.92	151	151
ABCG2	-0.19	0.43	-9999	-0.92	71	71
HIF1A	-0.009	0.068	-9999	-10000	0	0
TFF3	-0.57	0.51	-9999	-1	207	207
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	-0.23	63	63
MCL1	-0.19	0.42	-9999	-0.9	70	70
NDRG1	-0.19	0.42	-9999	-0.9	70	70
SERPINE1	-0.2	0.43	-9999	-0.9	76	76
FECH	-0.19	0.42	-9999	-0.9	70	70
FURIN	-0.19	0.42	-9999	-0.9	70	70
NCOA2	-0.066	0.24	-9999	-0.81	48	48
EP300	-0.062	0.18	-9999	-0.32	133	133
HMOX1	-0.19	0.42	-9999	-0.9	72	72
BHLHE40	-0.2	0.42	-9999	-0.91	72	72
BHLHE41	-0.19	0.42	-9999	-0.91	71	71
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.017	0.037	-9999	-10000	0	0
ENG	0.041	0.092	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.81	112	112
RORA	-0.19	0.42	-9999	-0.91	70	70
ABCB1	-0.076	0.19	-9999	-1.4	8	8
TFRC	-0.19	0.42	-9999	-0.91	71	71
CXCR4	-0.19	0.42	-9999	-0.9	70	70
TF	-0.24	0.49	-9999	-1	92	92
CITED2	-0.22	0.47	-9999	-1	83	83
HIF1A/ARNT	-0.29	0.38	-9999	-1	72	72
LDHA	-0.039	0.05	-9999	-10000	0	0
ETS1	-0.19	0.42	-9999	-0.9	70	70
PGK1	-0.19	0.42	-9999	-0.9	70	70
NOS2	-0.2	0.43	-9999	-0.9	80	80
ITGB2	-0.2	0.42	-9999	-0.92	71	71
ALDOA	-0.19	0.42	-9999	-0.9	70	70
Cbp/p300/CITED2	-0.32	0.51	-9999	-1	130	130
FOS	-0.2	0.36	-9999	-0.81	127	127
HK2	-0.19	0.42	-9999	-0.9	72	72
SP1	0.022	0.007	-9999	-10000	0	0
GCK	-0.38	0.71	-9999	-1.5	136	136
HK1	-0.19	0.42	-9999	-0.9	70	70
NPM1	-0.19	0.42	-9999	-0.9	70	70
EGLN1	-0.19	0.42	-9999	-0.9	71	71
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.19	0.42	-9999	-0.9	70	70
SMAD3	0.015	0.003	-9999	-10000	0	0
EDN1	-0.16	0.31	-9999	-0.73	64	64
IGFBP1	-0.2	0.42	-9999	-0.9	76	76
VEGFA	-0.16	0.38	-9999	-0.75	77	77
HIF1A/JAB1	-0.011	0.021	-9999	-10000	0	0
CP	-0.35	0.55	-9999	-1	152	152
CXCL12	-0.23	0.48	-9999	-1	90	90
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.19	0.42	-9999	-0.9	70	70
EGLN3	-0.2	0.44	-9999	-0.93	76	76
CA9	-0.2	0.42	-9999	-0.91	74	74
TERT	-0.2	0.42	-9999	-0.91	71	71
ENO1	-0.19	0.42	-9999	-0.9	70	70
PFKL	-0.19	0.42	-9999	-0.9	70	70
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.22	0.44	-9999	-0.88	97	97
ARNT	-0.01	0.067	-9999	-10000	0	0
HNF4A	-0.025	0.064	-9999	-0.35	10	10
ADFP	-0.2	0.41	-9999	-0.91	70	70
SLC2A1	-0.15	0.38	-9999	-0.74	78	78
LEP	-0.2	0.42	-9999	-0.92	70	70
HIF1A/ARNT/Cbp/p300	-0.29	0.36	-9999	-0.83	118	118
EPO	-0.14	0.33	-9999	-0.9	32	32
CREBBP	-0.062	0.18	-9999	-0.32	133	133
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.81	109	109
PFKFB3	-0.19	0.42	-9999	-0.9	71	71
NT5E	-0.2	0.43	-9999	-0.92	70	70

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.052	0.14	-9999	-0.56	11	11
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.7	63	63
EDN1	-0.044	0.12	-9999	-0.71	8	8
EDN3	-0.39	0.41	-9999	-0.81	244	244
EDN2	-0.014	0.11	-9999	-0.4	32	32
HRAS/GDP	-0.1	0.24	-9999	-0.54	80	80
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.086	0.18	-9999	-0.4	86	86
ADCY4	-0.097	0.19	-9999	-0.5	72	72
ADCY5	-0.16	0.25	-9999	-0.55	118	118
ADCY6	-0.097	0.19	-9999	-0.5	72	72
ADCY7	-0.097	0.19	-9999	-0.5	72	72
ADCY1	-0.1	0.21	-9999	-0.53	74	74
ADCY2	-0.14	0.24	-9999	-0.55	105	105
ADCY3	-0.097	0.19	-9999	-0.5	72	72
ADCY8	-0.2	0.21	-9999	-0.55	97	97
ADCY9	-0.097	0.19	-9999	-0.5	72	72
arachidonic acid secretion	-0.17	0.32	-9999	-0.65	133	133
ETB receptor/Endothelin-1/Gq/GTP	-0.097	0.22	-9999	-0.44	111	111
GNAO1	-0.017	0.15	-9999	-0.69	21	21
HRAS	0.01	0.021	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.018	0.16	-9999	-0.56	9	9
ETA receptor/Endothelin-1/Gs/GTP	-0.086	0.22	-9999	-0.53	72	72
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.069	0.17	-9999	-0.51	36	36
EDNRB	0.003	0.094	-9999	-0.75	7	7
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.15	0.24	-9999	-0.64	52	52
CYSLTR1	-0.063	0.18	-9999	-0.77	17	17
SLC9A1	-0.022	0.075	-9999	-0.32	6	6
mol:GDP	-0.12	0.26	-9999	-0.56	92	92
SLC9A3	-0.049	0.19	-9999	-0.8	21	21
RAF1	-0.15	0.3	-9999	-0.57	137	137
JUN	-0.28	0.52	-9999	-1.2	121	121
JAK2	-0.054	0.15	-9999	-0.57	13	13
mol:IP3	-0.11	0.23	-9999	-0.49	107	107
ETA receptor/Endothelin-1	-0.039	0.2	-9999	-0.55	19	19
PLCB1	0.009	0.038	-9999	-0.82	1	1
PLCB2	0.004	0.047	-9999	-0.32	10	10
ETA receptor/Endothelin-3	-0.32	0.33	-9999	-0.66	243	243
FOS	-0.25	0.47	-9999	-1	127	127
Gai/GDP	-0.002	0.13	-9999	-0.64	17	17
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.12	0.24	-9999	-0.6	56	56
BCAR1	0.013	0.001	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.48	107	107
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.094	0.28	-9999	-0.81	64	64
Gs family/GDP	-0.19	0.25	-9999	-0.57	120	120
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.46	98	98
MAPK14	-0.065	0.18	-9999	-0.44	45	45
TRPC6	-0.14	0.3	-9999	-0.74	62	62
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.012	0.037	-9999	-0.81	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.077	0.19	-9999	-0.4	85	85
ETB receptor/Endothelin-2	-0.026	0.1	-9999	-0.63	12	12
ETB receptor/Endothelin-3	-0.31	0.32	-9999	-0.63	245	245
ETB receptor/Endothelin-1	-0.021	0.12	-9999	-0.62	13	13
MAPK3	-0.23	0.43	-9999	-0.9	133	133
MAPK1	-0.23	0.43	-9999	-0.9	132	132
Rac1/GDP	-0.1	0.24	-9999	-0.53	80	80
cAMP biosynthetic process	-0.14	0.21	-9999	-0.55	77	77
MAPK8	-0.18	0.35	-9999	-0.66	124	124
SRC	0.013	0.015	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.008	0.078	-9999	-0.29	25	25
p130Cas/CRK/Src/PYK2	-0.13	0.3	-9999	-0.59	107	107
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.54	78	78
COL1A2	-0.039	0.17	-9999	-0.64	13	13
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.54	11	11
mol:DAG	-0.11	0.23	-9999	-0.49	107	107
MAP2K2	-0.18	0.35	-9999	-0.7	136	136
MAP2K1	-0.18	0.35	-9999	-0.7	137	137
EDNRA	-0.038	0.098	-9999	-0.52	5	5
positive regulation of muscle contraction	-0.036	0.12	-9999	-0.52	9	9
Gq family/GDP	-0.19	0.29	-9999	-0.66	118	118
HRAS/GTP	-0.13	0.26	-9999	-0.57	96	96
PRKCH	-0.1	0.22	-9999	-0.51	86	86
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.25	-9999	-0.55	96	96
PRKCB	-0.12	0.23	-9999	-0.52	91	91
PRKCE	-0.11	0.24	-9999	-0.53	86	86
PRKCD	-0.1	0.22	-9999	-0.51	85	85
PRKCG	-0.11	0.23	-9999	-0.52	86	86
regulation of vascular smooth muscle contraction	-0.3	0.55	-9999	-1.2	127	127
PRKCQ	-0.11	0.23	-9999	-0.52	89	89
PLA2G4A	-0.19	0.36	-9999	-0.72	133	133
GNA14	-0.19	0.36	-9999	-0.82	118	118
GNA15	-0.014	0.09	-9999	-0.32	36	36
GNA12	0.013	0	-9999	-10000	0	0
GNA11	-0.006	0.12	-9999	-0.82	10	10
Rac1/GTP	-0.018	0.16	-9999	-0.54	10	10
MMP1	-0.09	0.15	-9999	-10000	0	0

×

IGF1 pathway

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
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.13	0.23	-10000	0	-0.45	159	159
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	-0.45	159	159
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.22	-10000	0	-0.52	113	113
AKT1	-0.09	0.21	-10000	0	-0.41	114	114
BAD	-0.076	0.2	-10000	0	-0.7	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.13	0.23	-10000	0	-0.45	159	159
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.24	-10000	0	-0.45	159	159
RAF1	-0.067	0.19	-10000	0	-0.65	16	16
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.21	-10000	0	-0.42	159	159
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.15	0.25	-10000	0	-0.49	159	159
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
RPS6KB1	-0.09	0.21	-10000	0	-0.77	16	16
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.058	0.16	-10000	0	-0.53	16	16
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	-0.72	14	14
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.099	0.17	-10000	0	-0.42	113	113
IGF-1R heterotetramer	-0.019	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.15	0.22	-10000	0	-0.45	159	159
Crk/p130 Cas/Paxillin	-0.13	0.2	-10000	0	-0.43	113	113
IGF1R	-0.019	0.048	-10000	0	-10000	0	0
IGF1	-0.19	0.35	-10000	0	-0.81	119	119
IRS2/Crk	-0.11	0.22	-10000	0	-0.42	159	159
PI3K	-0.14	0.22	-10000	0	-0.43	159	159
apoptosis	0.058	0.18	0.57	16	-10000	0	16
HRAS/GDP	-0.001	0.013	-10000	0	-10000	0	0
PRKCD	-0.1	0.24	-10000	0	-0.53	113	113
RAF1/14-3-3 E	-0.049	0.17	-10000	0	-0.53	16	16
BAD/14-3-3	-0.063	0.19	-10000	0	-0.62	16	16
PRKCZ	-0.09	0.21	-10000	0	-0.41	114	114
Crk/p130 Cas/Paxillin/FAK1	-0.1	0.16	-10000	0	-0.63	16	16
PTPN1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.12	0.25	-10000	0	-0.56	113	113
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.19	-10000	0	-0.46	113	113
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.13	0.23	-10000	0	-0.45	159	159
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.13	0.24	-10000	0	-0.45	159	159
IRS1	-0.14	0.25	-10000	0	-0.49	159	159
IRS2	-0.13	0.23	-10000	0	-0.45	159	159
IGF-1R heterotetramer/IGF1	-0.16	0.27	-10000	0	-0.65	113	113
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.1	0.23	-10000	0	-0.44	114	114
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.24	-10000	0	-0.53	114	114
SHC1	0.013	0	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	0.045	0.093	-10000	0	-10000	0	0
SMARCC2	0.014	0.014	-10000	0	-10000	0	0
SMARCC1	0.014	0.014	-10000	0	-10000	0	0
TBX21	-0.15	0.28	-10000	0	-0.76	58	58
SUMO2	0.014	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.05	-10000	0	-0.3	12	12
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.003	0.091	-10000	0	-0.81	6	6
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.33	53	-0.49	6	59
PRL	-0.086	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.24	0.31	0.58	157	-0.49	23	180
RELA	-0.029	0.087	-10000	0	-10000	0	0
FGG	0.24	0.19	0.51	112	-10000	0	112
GR beta/TIF2	0.078	0.24	0.35	71	-0.56	48	119
IFNG	-0.49	0.51	-10000	0	-1.1	154	154
apoptosis	0.034	0.24	0.49	69	-0.51	5	74
CREB1	0.012	0.023	-10000	0	-10000	0	0
histone acetylation	-0.068	0.17	-10000	0	-0.38	76	76
BGLAP	-0.096	0.15	-10000	0	-0.53	12	12
GR/PKAc	0.13	0.1	0.34	31	-0.4	1	32
NF kappa B1 p50/RelA	-0.061	0.16	-10000	0	-0.45	27	27
SMARCD1	0.014	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.095	0.27	104	-10000	0	104
GATA3	-0.026	0.18	-10000	0	-0.78	27	27
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.49	74	74
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.061	0.24	0.5	51	-0.73	5	56
CSN2	0.2	0.14	0.41	104	-10000	0	104
BRG1/BAF155/BAF170/BAF60A	0.022	0.048	-10000	0	-0.34	2	2
NFATC1	0.001	0.11	-10000	0	-0.81	9	9
POU2F1	0.013	0.015	-10000	0	-0.3	1	1
CDKN1A	0.025	0.052	-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	-0.33	312	312
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.044	0.16	0.32	21	-0.46	17	38
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.078	0.45	0.48	53	-0.88	107	160
JUN	-0.33	0.3	-10000	0	-0.68	181	181
IL4	-0.12	0.18	-10000	0	-0.68	21	21
CDK5R1	0.011	0.027	-10000	0	-0.32	3	3
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.36	0.41	-10000	0	-0.81	187	187
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.35	29	-0.47	5	34
cortisol/GR alpha (monomer)	0.36	0.3	0.68	187	-10000	0	187
NCOA2	-0.067	0.24	-10000	0	-0.81	48	48
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.35	-10000	0	-0.84	127	127
AP-1/NFAT1-c-4	-0.55	0.48	-10000	0	-0.95	241	241
AFP	-0.22	0.22	-10000	0	-0.63	67	67
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.47	59	-10000	0	59
TP53	0.033	0.023	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.47	0.37	-10000	0	-0.8	200	200
KRT14	-0.23	0.17	-10000	0	-0.6	22	22
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.064	0.065	-10000	0	-0.28	1	1
HDAC1	0.011	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.013	-10000	0	-10000	0	0
AP-1	-0.55	0.48	-10000	0	-0.96	241	241
MAPK14	0.014	0.012	-10000	0	-10000	0	0
MAPK10	0.013	0.04	-10000	0	-0.82	1	1
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.53	0.52	-10000	0	-1	196	196
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	-0.3	12	12
CGA	-0.12	0.16	-10000	0	-0.56	18	18
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.36	223	-10000	0	223
MAPK3	0.015	0.013	-10000	0	-10000	0	0
MAPK1	0.014	0.012	-10000	0	-10000	0	0
ICAM1	-0.24	0.26	-10000	0	-0.68	88	88
NFKB1	-0.031	0.096	-10000	0	-0.94	1	1
MAPK8	-0.19	0.21	-10000	0	-0.48	118	118
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.029	0.25	0.5	68	-0.53	5	73
BAX	0.029	0.034	-10000	0	-10000	0	0
POMC	-0.54	0.69	-10000	0	-1.5	138	138
EP300	0.065	0.065	-10000	0	-0.28	1	1
cortisol/GR alpha (dimer)/p53	0.32	0.24	0.59	177	-10000	0	177
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.072	0.24	31	-10000	0	31
SGK1	0.1	0.22	-10000	0	-1.4	10	10
IL13	-0.29	0.25	-10000	0	-0.7	89	89
IL6	-0.37	0.52	-10000	0	-1.2	124	124
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.66	60	60
IL2	-0.36	0.27	-10000	0	-0.69	142	142
CDK5	0.013	0.007	-10000	0	-10000	0	0
PRKACB	0.012	0.037	-10000	0	-0.81	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.26	0.32	-10000	0	-0.76	94	94
CDK5R1/CDK5	0.007	0.025	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.023	0.12	-10000	0	-0.63	2	2
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.56	167	-10000	0	167
SMARCA4	0.014	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.4	119	-0.39	1	120
NF kappa B1 p50/RelA/Cbp	0.028	0.16	-10000	0	-0.45	10	10
JUN (dimer)	-0.33	0.3	-10000	0	-0.67	181	181
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.41	-10000	0	-1	94	94
NR3C1	0.21	0.19	0.48	125	-10000	0	125
NR4A1	-0.31	0.41	-10000	0	-0.75	212	212
TIF2/SUV420H1	-0.061	0.18	-10000	0	-0.62	48	48
MAPKKK cascade	0.034	0.24	0.49	69	-0.51	5	74
cortisol/GR alpha (dimer)/Src-1	0.32	0.24	0.58	178	-10000	0	178
PBX1	0.014	0.004	-10000	0	-10000	0	0
POU1F1	0.007	0.008	-10000	0	-10000	0	0
SELE	-0.33	0.5	-10000	0	-1.2	104	104
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.4	116	-0.4	1	117
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.56	167	-10000	0	167
mol:cortisol	0.2	0.19	0.4	195	-10000	0	195
MMP1	-0.21	0.15	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.064	-10000	0	-0.82	3	3
EFNB1	0.001	0.12	-10000	0	-0.63	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.24	0.24	-10000	0	-0.52	201	201
Ephrin B2/EPHB1-2	-0.19	0.24	-10000	0	-0.5	188	188
neuron projection morphogenesis	-0.23	0.23	-10000	0	-0.49	201	201
Ephrin B1/EPHB1-2/Tiam1	-0.26	0.26	-10000	0	-0.56	201	201
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.005	0.088	-10000	0	-0.78	6	6
YES1	-0.01	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/NCK2	-0.18	0.24	-10000	0	-0.46	201	201
PI3K	0.003	0.12	-10000	0	-1	6	6
mol:GDP	-0.25	0.26	-10000	0	-0.55	201	201
ITGA2B	-0.075	0.26	-10000	0	-0.81	53	53
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.01	0.11	-10000	0	-1	6	6
MAP3K7	-0.012	0.091	-10000	0	-0.83	6	6
FGR	-0.012	0.11	-10000	0	-1	6	6
TIAM1	-0.17	0.16	-10000	0	-0.81	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.044	0.2	-10000	0	-0.53	66	66
LYN	-0.01	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.014	0.1	-10000	0	-0.96	6	6
Ephrin B1/EPHB1-2	-0.019	0.098	-10000	0	-0.89	6	6
SRC	-0.012	0.11	-10000	0	-1	6	6
ITGB3	-0.012	0.14	-10000	0	-0.81	15	15
EPHB1	-0.3	0.4	-10000	0	-0.82	186	186
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	-0.084	0.23	-10000	0	-0.67	62	62
BLK	-0.066	0.14	-10000	0	-1.1	6	6
HCK	-0.013	0.11	-10000	0	-1	6	6
regulation of stress fiber formation	0.18	0.24	0.46	201	-10000	0	201
MAPK8	0.003	0.13	-10000	0	-0.77	12	12
Ephrin B1/EPHB1-2/RGS3	-0.18	0.24	-10000	0	-0.46	201	201
endothelial cell migration	-0.006	0.08	-10000	0	-0.72	6	6
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.005	0.1	-10000	0	-0.93	6	6
regulation of focal adhesion formation	0.18	0.24	0.46	201	-10000	0	201
chemotaxis	0.18	0.24	0.46	201	-10000	0	201
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
Rac1/GTP	-0.24	0.24	-10000	0	-0.51	201	201
angiogenesis	-0.019	0.097	-10000	0	-0.88	6	6
LCK	-0.015	0.12	-10000	0	-1	6	6

×

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	78	78
FYN	-0.11	0.35	-10000	0	-0.79	86	86
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.66	89	89
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.056	0.22	-10000	0	-0.47	90	90
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.051	-10000	0	-0.15	46	46
MAP3K8	0.002	0.098	-10000	0	-0.81	7	7
mol:Ca2+	-0.031	0.05	-10000	0	-0.12	108	108
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	92	92
TRPV6	-0.17	0.34	-10000	0	-0.79	110	110
CD28	-0.045	0.19	-10000	0	-0.59	48	48
SHC1	-0.12	0.34	-10000	0	-0.8	85	85
receptor internalization	-0.14	0.38	-10000	0	-0.83	95	95
PRF1	-0.12	0.35	-10000	0	-0.9	70	70
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.038	0.18	-10000	0	-0.38	89	89
LAT	-0.12	0.35	-10000	0	-0.82	85	85
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.093	0.27	-10000	0	-0.69	75	75
CD3E	-0.068	0.24	-10000	0	-0.74	54	54
CD3G	-0.14	0.32	-10000	0	-0.78	99	99
RASGRP2	0	0.031	-10000	0	-0.14	10	10
RASGRP1	-0.053	0.22	-10000	0	-0.46	97	97
HLA-A	0.011	0.021	-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	0.009	0.068	-10000	0	-0.12	71	71
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.057	0.091	-10000	0	-0.26	65	65
PRKCA	-0.06	0.13	-10000	0	-0.29	101	101
GRAP2	-0.045	0.21	-10000	0	-0.75	38	38
mol:IP3	-0.053	0.23	0.27	85	-0.46	89	174
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.15	0.42	-10000	0	-0.97	82	82
ORAI1	0.087	0.16	0.39	103	-10000	0	103
CSK	-0.12	0.35	-10000	0	-0.83	85	85
B7 family/CD28	-0.2	0.35	-10000	0	-0.75	115	115
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.16	0.42	-10000	0	-0.94	93	93
PTPN6	-0.12	0.36	-10000	0	-0.83	85	85
VAV1	-0.13	0.35	-10000	0	-0.79	90	90
Monovalent TCR/CD3	-0.16	0.4	-10000	0	-0.72	124	124
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.82	89	89
PAG1	-0.12	0.35	-10000	0	-0.83	85	85
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.16	0.42	-10000	0	-0.94	92	92
CD80	-0.071	0.25	-10000	0	-0.8	51	51
CD86	-0.009	0.1	-10000	0	-0.41	26	26
PDK1/CARD11/BCL10/MALT1	-0.07	0.11	-10000	0	-0.3	70	70
HRAS	0.012	0.021	-10000	0	-0.31	2	2
GO:0035030	-0.11	0.29	-10000	0	-0.59	115	115
CD8A	-0.052	0.22	-10000	0	-0.81	39	39
CD8B	-0.091	0.27	-10000	0	-0.72	71	71
PTPRC	-0.035	0.18	-10000	0	-0.59	39	39
PDK1/PKC theta	-0.071	0.27	-10000	0	-0.59	89	89
CSK/PAG1	-0.11	0.34	-10000	0	-0.8	84	84
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	91	91
STIM1	0.047	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.007	0.091	-10000	0	-0.18	57	57
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.43	-10000	0	-0.94	93	93
mol:DAG	-0.072	0.18	-10000	0	-0.41	90	90
RAP1A/GDP	0.006	0.03	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.024	0.16	-10000	0	-0.62	30	30
cytotoxic T cell degranulation	-0.11	0.33	-10000	0	-0.85	70	70
RAP1A/GTP	-0.003	0.009	-10000	0	-0.068	6	6
mol:PI-3-4-5-P3	-0.076	0.26	-10000	0	-0.57	92	92
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.083	0.29	0.3	75	-0.62	89	164
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.026	0.17	-10000	0	-0.62	31	31
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.26	-10000	0	-0.62	90	90
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.01	0.053	-10000	0	-0.81	2	2
CD8 heterodimer	-0.11	0.29	-10000	0	-0.75	77	77
CARD11	-0.07	0.17	-10000	0	-0.36	109	109
PRKCB	-0.059	0.13	-10000	0	-0.3	89	89
PRKCE	-0.053	0.12	-10000	0	-0.29	88	88
PRKCQ	-0.094	0.31	-10000	0	-0.69	89	89
LCP2	0.008	0.043	-10000	0	-0.31	9	9
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.042	0.18	-10000	0	-0.4	90	90
IKK complex	0.013	0.068	-10000	0	-0.11	60	60
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.018	0.14	-10000	0	-0.3	72	72
PDPK1	-0.049	0.21	-10000	0	-0.45	88	88
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.45	-10000	0	-1.1	86	86

×

IL23-mediated signaling events

Figure S24. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S24. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.21	0.55	-10000	0	-1.3	81	81
IL23A	-0.22	0.56	-10000	0	-1.3	86	86
NF kappa B1 p50/RelA/I kappa B alpha	-0.29	0.46	-10000	0	-1.2	91	91
positive regulation of T cell mediated cytotoxicity	-0.24	0.61	-10000	0	-1.3	96	96
ITGA3	-0.19	0.51	-10000	0	-1.1	87	87
IL17F	-0.1	0.34	-10000	0	-0.74	73	73
IL12B	-0.003	0.11	-10000	0	-0.58	12	12
STAT1 (dimer)	-0.23	0.58	-10000	0	-1.3	90	90
CD4	-0.19	0.5	-10000	0	-1.1	85	85
IL23	-0.22	0.53	-10000	0	-1.2	83	83
IL23R	-0.003	0.099	-10000	0	-10000	0	0
IL1B	-0.23	0.58	-10000	0	-1.3	90	90
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.19	0.5	-10000	0	-1.1	85	85
TYK2	0.014	0.023	-10000	0	-10000	0	0
STAT4	-0.025	0.14	-10000	0	-0.81	11	11
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.028	0.18	-10000	0	-0.78	25	25
IL12RB1	-0.024	0.13	-10000	0	-0.39	48	48
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
IL12Rbeta1/TYK2	-0.011	0.1	-10000	0	-0.67	6	6
IL23R/JAK2	0	0.13	-10000	0	-0.63	2	2
positive regulation of chronic inflammatory response	-0.24	0.61	-10000	0	-1.3	96	96
natural killer cell activation	0.001	0.009	0.036	1	-10000	0	1
JAK2	0.019	0.061	-10000	0	-0.84	2	2
PIK3R1	0.014	0	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
RELA	0.013	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.21	0.5	-10000	0	-1.1	84	84
ALOX12B	-0.21	0.51	-10000	0	-1.1	87	87
CXCL1	-0.22	0.53	-10000	0	-1.2	85	85
T cell proliferation	-0.24	0.61	-10000	0	-1.3	96	96
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.058	0.28	-10000	0	-0.58	61	61
PI3K	-0.3	0.48	-10000	0	-1.2	90	90
IFNG	-0.02	0.055	-10000	0	-0.13	73	73
STAT3 (dimer)	-0.28	0.44	-10000	0	-1.1	87	87
IL18R1	-0.03	0.14	-10000	0	-0.42	47	47
IL23/IL23R/JAK2/TYK2/SOCS3	-0.095	0.33	-10000	0	-0.73	62	62
IL18/IL18R	-0.067	0.18	-10000	0	-0.56	49	49
macrophage activation	-0.014	0.018	-10000	0	-0.044	88	88
TNF	-0.26	0.62	-10000	0	-1.3	103	103
STAT3/STAT4	-0.31	0.49	-10000	0	-1.2	91	91
STAT4 (dimer)	-0.24	0.58	-10000	0	-1.3	91	91
IL18	-0.039	0.15	-10000	0	-0.41	60	60
IL19	-0.19	0.5	-10000	0	-1.1	86	86
STAT5A (dimer)	-0.23	0.57	-10000	0	-1.3	93	93
STAT1	0.006	0.05	-10000	0	-0.31	12	12
SOCS3	-0.026	0.18	-10000	0	-0.79	24	24
CXCL9	-0.3	0.64	-10000	0	-1.4	112	112
MPO	-0.2	0.51	-10000	0	-1.1	87	87
positive regulation of humoral immune response	-0.24	0.61	-10000	0	-1.3	96	96
IL23/IL23R/JAK2/TYK2	-0.28	0.74	-10000	0	-1.5	96	96
IL6	-0.31	0.64	-10000	0	-1.4	118	118
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	-0.23	0.57	-10000	0	-1.3	90	90
keratinocyte proliferation	-0.24	0.61	-10000	0	-1.3	96	96
NOS2	-0.2	0.5	-10000	0	-1.1	89	89

×

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	-0.087	0.15	-9999	-0.31	152	152
GPC2	-0.009	0.082	-9999	-0.31	34	34
GPC2/Midkine	-0.076	0.11	-9999	-0.41	13	13
neuron projection morphogenesis	-0.076	0.11	-9999	-0.41	13	13

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.26	0.32	-9999	-0.59	217	217
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.047	0.21	-9999	-0.69	42	42
SMAD9	-0.22	0.28	-9999	-0.59	162	162
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.092	0.2	-9999	-0.55	29	29
BMP7/USAG1	-0.32	0.31	-9999	-0.62	254	254
SMAD5/SKI	-0.081	0.19	-9999	-0.52	28	28
SMAD1	0.019	0.044	-9999	-10000	0	0
BMP2	-0.017	0.16	-9999	-0.81	18	18
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	-0.81	161	161
BMPR1A-1B/BAMBI	-0.18	0.26	-9999	-0.55	161	161
AHSG	-0.018	0.086	-9999	-0.31	39	39
CER1	0	0.003	-9999	-10000	0	0
BMP2-4/CER1	-0.037	0.13	-9999	-0.55	31	31
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.073	0.19	-9999	-0.62	31	31
BMP2-4 (homodimer)	-0.042	0.15	-9999	-0.62	31	31
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	161	161
RGMA	-0.017	0.16	-9999	-0.81	18	18
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.085	0.18	-9999	-0.56	29	29
BMP2-4/USAG1	-0.31	0.3	-9999	-0.57	270	270
SMAD6/SMURF1/SMAD5	-0.081	0.19	-9999	-0.52	28	28
SOSTDC1	-0.41	0.41	-9999	-0.81	254	254
BMP7/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	161	161
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.011	0.029	-9999	-0.31	4	4
HFE2	0.001	0.032	-9999	-0.31	5	5
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.047	0.15	-9999	-0.55	40	40
SMAD5/SMAD5/SMAD4	-0.081	0.19	-9999	-0.52	28	28
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.091	0.14	-9999	-0.48	29	29
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.017	0.058	-9999	-0.39	1	1
SMAD1/SKI	0.026	0.042	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.048	0.14	-9999	-0.56	31	31
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.2	0.35	-9999	-0.72	140	140
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.007	0.059	-9999	-0.54	6	6
BMPR1A-1B (homodimer)	-0.2	0.29	-9999	-0.62	161	161
CHRDL1	-0.57	0.38	-9999	-0.81	350	350
ENDOFIN/SMAD1	0.026	0.042	-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	-0.36	20	20
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.42	0.28	-9999	-0.57	356	356
BMP2-4/GREM1	-0.17	0.27	-9999	-0.59	132	132
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.18	0.27	-9999	-0.55	162	162
SMAD1/SMAD6	0.026	0.042	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.013	0	-9999	-10000	0	0
BMP6	0.011	0.029	-9999	-0.31	4	4
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.064	0.16	-9999	-0.49	29	29
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.026	0.042	-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	0.003	0.091	-9999	-0.81	6	6
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.19	0.31	-9999	-0.78	85	85
CHRD	-0.003	0.12	-9999	-0.81	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.09	0.19	-9999	-0.6	29	29
BMP4	-0.013	0.14	-9999	-0.64	20	20
FST	-0.19	0.35	-9999	-0.78	127	127
BMP2-4/NOG	-0.074	0.18	-9999	-0.55	62	62
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.15	0.21	-9999	-0.46	161	161

×

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	-0.35	14	14
SVIL	-0.007	0.031	-10000	0	-10000	0	0
ZNF318	0.062	0.092	-10000	0	-0.81	1	1
JMJD2C	-0.064	0.069	-10000	0	-0.12	282	282
T-DHT/AR/Ubc9	-0.28	0.3	-10000	0	-0.61	209	209
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	0.024	-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	-0.79	7	7
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.06	-10000	0	-0.81	2	2
GSN	-0.006	0.03	-10000	0	-10000	0	0
NCOA2	-0.069	0.24	-10000	0	-0.82	48	48
NCOA6	-0.007	0.047	-10000	0	-0.81	1	1
DNA-PK	0.059	0.084	0.26	1	-10000	0	1
NCOA4	0.012	0.003	-10000	0	-10000	0	0
PIAS3	-0.002	0.024	-10000	0	-10000	0	0
cell proliferation	-0.011	0.15	-10000	0	-1	7	7
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	-0.66	217	217
FHL2	-0.15	0.36	-10000	0	-1.3	38	38
RANBP9	-0.005	0.029	-10000	0	-10000	0	0
JMJD1A	0.002	0.037	-10000	0	-0.12	36	36
CDK6	0.01	0.064	-10000	0	-0.81	3	3
TGFB1I1	-0.007	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.29	0.3	-10000	0	-0.62	212	212
XRCC6	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR	-0.33	0.31	-10000	0	-0.63	235	235
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	-0.1	0.16	-10000	0	-0.31	136	136
SRF	0.028	0.039	-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	142	142
TMF1	0.006	0.053	-10000	0	-0.81	2	2
HNRNPA1	0.032	0.028	-10000	0	-10000	0	0
AOF2	-0.022	0.034	-10000	0	-0.075	142	142
APPL1	0.052	0.043	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.27	0.29	-10000	0	-0.6	209	209
AR	-0.38	0.42	-10000	0	-0.86	209	209
UBA3	0.009	0.006	-10000	0	-10000	0	0
PATZ1	0.032	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	0.037	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	-0.56	209	209
RPS6KA3	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.28	0.29	-10000	0	-0.61	211	211
LATS2	0.03	0.047	-10000	0	-0.81	1	1
T-DHT/AR/PRX1	-0.24	0.28	-10000	0	-0.56	209	209
Cyclin D3/CDK11 p58	0.001	0.004	-10000	0	-10000	0	0
VAV3	-0.012	0.093	-10000	0	-0.82	6	6
KLK2	-0.77	0.62	-10000	0	-1.3	281	281
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.66	216	216
TMPRSS2	-0.18	0.31	-10000	0	-1.3	34	34
CCND1	0.001	0.05	-10000	0	-0.31	12	12
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.031	0.041	-10000	0	-0.082	165	165
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	-0.61	213	213
CMTM2	0.014	0.026	-10000	0	-0.31	3	3
SNURF	-0.038	0.2	-10000	0	-0.81	30	30
ZMIZ1	-0.013	0.051	-10000	0	-0.8	1	1
CCND3	0.014	0.002	-10000	0	-10000	0	0
TGIF1	0.032	0.028	-10000	0	-10000	0	0
FKBP4	-0.005	0.029	-10000	0	-10000	0	0

×

Arf6 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
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.042	0.11	-9999	-0.47	12	12
EGFR	0.005	0.083	-9999	-0.81	5	5
EPHA2	0.011	0.025	-9999	-0.31	3	3
USP6	0.011	0.025	-9999	-0.31	3	3
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.1	0.23	-9999	-0.62	77	77
ARRB2	-0.044	0.15	-9999	-0.44	61	61
mol:GTP	0.02	0.012	-9999	-10000	0	0
ARRB1	0.012	0.037	-9999	-0.81	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.01	0.053	-9999	-0.82	2	2
EGF	-0.11	0.29	-9999	-0.78	78	78
somatostatin receptor activity	0	0	-9999	-0.001	135	135
ARAP2	0.01	0.053	-9999	-0.81	2	2
mol:GDP	-0.12	0.14	-9999	-0.31	135	135
mol:PI-3-4-5-P3	0	0	-9999	-0.001	70	70
ITGA2B	-0.075	0.26	-9999	-0.81	53	53
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	-0.16	0.24	-9999	-0.68	74	74
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.32	137	137
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.086	0.2	-9999	-0.54	77	77
ADRB2	-0.007	0.13	-9999	-0.81	12	12
receptor agonist activity	0	0	-9999	0	144	144
actin filament binding	0	0	-9999	-0.001	134	134
SRC	0.013	0.015	-9999	-10000	0	0
ITGB3	-0.012	0.14	-9999	-0.81	15	15
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	118	118
ARF6/GDP	0	0.068	-9999	-0.33	2	2
ARF6/GDP/GULP/ACAP1	-0.18	0.2	-9999	-0.49	116	116
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.067	0.18	-9999	-0.54	62	62
ACAP1	-0.001	0.078	-9999	-0.36	19	19
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.079	0.22	-9999	-0.67	61	61
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.11	0.3	-9999	-0.81	74	74
CYTH3	0.009	0.041	-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	112	112
endosomal lumen acidification	0	0	-9999	-0.001	142	142
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.32	-9999	-0.81	89	89
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	21	21
MET	-0.1	0.16	-9999	-0.31	179	179
GNA14	-0.18	0.35	-9999	-0.81	118	118
GNA15	-0.011	0.09	-9999	-0.32	36	36
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	127	127
GNA11	-0.004	0.12	-9999	-0.81	10	10
LHCGR	-0.098	0.27	-9999	-0.76	68	68
AGTR1	-0.32	0.4	-9999	-0.81	200	200
desensitization of G-protein coupled receptor protein signaling pathway	-0.078	0.22	-9999	-0.67	61	61
IPCEF1/ARNO	-0.057	0.16	-9999	-0.43	77	77
alphaIIb/beta3 Integrin	-0.084	0.23	-9999	-0.67	62	62

×

Syndecan-1-mediated signaling events

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
TGFB1	0.008	0.041	-9999	-0.31	8	8
CCL5	-0.047	0.21	-9999	-0.69	42	42
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.16	-9999	-0.48	51	51
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.09	0.16	-9999	-0.56	29	29
Syndecan-1/Syntenin	-0.09	0.16	-9999	-0.61	24	24
MAPK3	-0.067	0.14	-9999	-0.6	19	19
HGF/MET	-0.16	0.24	-9999	-0.68	74	74
TGFB1/TGF beta receptor Type II	0.008	0.041	-9999	-0.31	8	8
BSG	0.013	0.015	-9999	-0.31	1	1
keratinocyte migration	-0.088	0.15	-9999	-0.55	29	29
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.64	57	57
Syndecan-1/CD147	-0.079	0.15	-9999	-0.59	23	23
Syndecan-1/Syntenin/PIP2	-0.097	0.14	-9999	-0.59	24	24
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.096	0.14	-9999	-0.57	24	24
MMP7	-0.17	0.22	-9999	-0.37	243	243
HGF	-0.11	0.3	-9999	-0.81	74	74
Syndecan-1/CASK	-0.098	0.15	-9999	-0.46	51	51
Syndecan-1/HGF/MET	-0.2	0.24	-9999	-0.63	89	89
regulation of cell adhesion	-0.057	0.14	-9999	-0.57	19	19
HPSE	-0.016	0.13	-9999	-0.51	28	28
positive regulation of cell migration	-0.1	0.16	-9999	-0.48	51	51
SDC1	-0.1	0.16	-9999	-0.48	51	51
Syndecan-1/Collagen	-0.1	0.16	-9999	-0.48	51	51
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.1	0.16	-9999	-0.31	179	179
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.58	80	80
MAPK1	-0.067	0.14	-9999	-0.6	19	19
homophilic cell adhesion	-0.1	0.16	-9999	-0.47	51	51
MMP1	-0.14	0.16	-9999	-0.31	226	226

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.026	0.16	-10000	0	-0.44	31	31
TBX21	-0.12	0.44	-10000	0	-1.1	67	67
B2M	0.012	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.02	-10000	0	-10000	0	0
IL12RB1	-0.022	0.13	-10000	0	-0.39	48	48
GADD45B	-0.092	0.38	-10000	0	-0.94	60	60
IL12RB2	-0.015	0.16	-10000	0	-0.72	21	21
GADD45G	-0.075	0.34	-10000	0	-0.88	50	50
natural killer cell activation	0.002	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	0.15	-10000	0	-0.4	60	60
IL2RA	-0.047	0.2	-10000	0	-0.81	28	28
IFNG	-0.11	0.28	-10000	0	-0.72	79	79
STAT3 (dimer)	-0.073	0.32	-10000	0	-0.73	70	70
HLA-DRB5	-0.04	0.13	-10000	0	-0.34	71	71
FASLG	-0.14	0.48	-10000	0	-1.1	78	78
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.82	76	76
CD4	-0.002	0.063	-10000	0	-0.31	19	19
SOCS1	0.008	0.049	-10000	0	-0.39	6	6
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.097	0.27	-10000	0	-0.7	75	75
CD3E	-0.072	0.24	-10000	0	-0.74	54	54
CD3G	-0.15	0.32	-10000	0	-0.78	99	99
IL12Rbeta2/JAK2	-0.002	0.13	-10000	0	-0.63	19	19
CCL3	-0.11	0.43	-10000	0	-1.1	60	60
CCL4	-0.15	0.51	-10000	0	-1.3	65	65
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
IL18/IL18R	-0.032	0.2	-10000	0	-0.56	49	49
NOS2	-0.089	0.34	-10000	0	-0.81	63	63
IL12/IL12R/TYK2/JAK2/SPHK2	-0.024	0.15	-10000	0	-0.41	32	32
IL1R1	-0.088	0.37	-10000	0	-0.95	54	54
IL4	0.002	0.023	-10000	0	-10000	0	0
JAK2	0.012	0.057	-10000	0	-0.82	2	2
EntrezGene:6957	-0.006	0.014	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.25	0.56	-10000	0	-1.2	106	106
RAB7A	-0.042	0.29	-10000	0	-0.68	52	52
lysosomal transport	-0.037	0.28	-10000	0	-0.64	53	53
FOS	-0.4	0.65	-10000	0	-1.3	159	159
STAT4 (dimer)	-0.08	0.35	-10000	0	-0.81	65	65
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.86	98	98
GZMA	-0.11	0.41	-10000	0	-1	58	58
GZMB	-0.1	0.39	-10000	0	-1	54	54
HLX	0.004	0.054	-10000	0	-0.31	14	14
LCK	-0.11	0.43	-10000	0	-0.94	76	76
TCR/CD3/MHC II/CD4	-0.19	0.35	-10000	0	-0.62	136	136
IL2/IL2R	-0.081	0.22	-10000	0	-0.67	48	48
MAPK14	-0.07	0.35	-10000	0	-0.78	68	68
CCR5	-0.1	0.41	-10000	0	-1.1	53	53
IL1B	-0.044	0.22	-10000	0	-0.76	39	39
STAT6	-0.005	0.11	0.24	2	-0.24	27	29
STAT4	-0.025	0.14	-10000	0	-0.81	11	11
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.05	-10000	0	-0.31	12	12
NFKB1	0.012	0.037	-10000	0	-0.81	1	1
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.003	0.1	-10000	0	-0.58	12	12
CD8A	-0.052	0.22	-10000	0	-0.81	39	39
CD8B	-0.092	0.27	-10000	0	-0.71	71	71
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.025	0.16	0.43	31	-10000	0	31
IL2RB	-0.014	0.13	-10000	0	-0.5	27	27
proteasomal ubiquitin-dependent protein catabolic process	-0.068	0.32	-10000	0	-0.74	64	64
IL2RG	-0.048	0.19	-10000	0	-0.52	57	57
IL12	-0.057	0.21	-10000	0	-0.63	57	57
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.028	0.16	-10000	0	-0.62	30	30
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	-0.073	0.26	-10000	0	-0.79	54	54
IL12/IL12R/TYK2/JAK2	-0.13	0.48	-10000	0	-1	77	77
MAP2K3	-0.072	0.34	-10000	0	-0.77	68	68
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.079	0.36	-10000	0	-0.78	72	72
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.029	0.13	-10000	0	-0.4	48	48
IL18RAP	-0.025	0.18	-10000	0	-0.78	25	25
IL12Rbeta1/TYK2	-0.006	0.1	-10000	0	-0.65	6	6
EOMES	-0.15	0.43	-10000	0	-1.5	45	45
STAT1 (dimer)	-0.13	0.37	-10000	0	-0.77	96	96
T cell proliferation	-0.05	0.27	-10000	0	-0.58	66	66
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.026	0.14	-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	-0.15	0.24	-10000	0	-0.67	66	66
ATF2	-0.075	0.33	-10000	0	-0.73	66	66

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.087	0.2	-10000	0	-0.55	77	77
cell-cell adhesion	0.15	0.18	0.54	11	-10000	0	11
Ephrin B/EPHB2/RasGAP	-0.013	0.067	-10000	0	-0.46	10	10
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.08	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.21	0.26	-10000	0	-0.55	186	186
HRAS/GDP	-0.13	0.17	-10000	0	-0.49	13	13
Ephrin B/EPHB1/GRB7	-0.2	0.24	-10000	0	-0.5	191	191
Endophilin/SYNJ1	0.025	0.07	-10000	0	-0.43	10	10
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.18	0.23	-10000	0	-0.47	191	191
endothelial cell migration	-0.003	0.036	-10000	0	-0.46	3	3
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.04	0.12	-10000	0	-0.31	82	82
PAK1	0.033	0.072	-10000	0	-0.43	10	10
HRAS	0.012	0.021	-10000	0	-0.31	2	2
RRAS	0.025	0.072	-10000	0	-0.44	10	10
DNM1	-0.014	0.15	-10000	0	-0.78	17	17
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.15	0.24	-10000	0	-0.44	191	191
lamellipodium assembly	-0.15	0.18	-10000	0	-0.54	11	11
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.1	0.18	-10000	0	-0.43	11	11
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.064	-10000	0	-0.81	3	3
EPHB3	-0.18	0.16	-10000	0	-10000	0	0
EPHB1	-0.3	0.4	-10000	0	-0.81	186	186
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.066	0.17	-10000	0	-0.46	11	11
Ephrin B/EPHB2	-0.014	0.069	-10000	0	-0.46	10	10
Ephrin B/EPHB3	-0.085	0.085	-10000	0	-0.56	7	7
JNK cascade	-0.14	0.24	-10000	0	-0.45	188	188
Ephrin B/EPHB1	-0.19	0.23	-10000	0	-0.48	191	191
RAP1/GDP	-0.05	0.15	-10000	0	-0.52	3	3
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.01	0.11	-10000	0	-0.45	25	25
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.19	0.24	-10000	0	-0.5	188	188
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.15	0.19	-10000	0	-0.51	18	18
Rap1/GTP	-0.15	0.18	-10000	0	-0.55	11	11
axon guidance	-0.086	0.2	-10000	0	-0.55	77	77
MAPK3	-0.075	0.16	-10000	0	-0.53	2	2
MAPK1	-0.075	0.16	-10000	0	-0.53	2	2
Rac1/GDP	-0.041	0.17	-10000	0	-0.46	7	7
actin cytoskeleton reorganization	-0.1	0.13	-10000	0	-0.45	6	6
CDC42/GDP	-0.041	0.17	-10000	0	-0.46	7	7
PI3K	-0.003	0.036	-10000	0	-0.46	3	3
EFNA5	-0.11	0.3	-10000	0	-0.81	76	76
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.054	-10000	0	-0.33	10	10
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.14	0.18	-10000	0	-0.52	12	12
PTK2	0.04	0.051	-10000	0	-10000	0	0
MAP4K4	-0.15	0.24	-10000	0	-0.46	188	188
SRC	0.013	0.015	-10000	0	-10000	0	0
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.065	0.18	-10000	0	-0.54	3	3
MAP2K1	-0.087	0.17	-10000	0	-0.4	11	11
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.19	0.24	-10000	0	-0.49	188	188
cell migration	-0.083	0.19	-10000	0	-0.43	11	11
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.026	0.072	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.022	0.17	-10000	0	-0.44	62	62
HRAS/GTP	-0.16	0.2	-10000	0	-0.4	193	193
Ephrin B1/EPHB1-2	-0.19	0.24	-10000	0	-0.5	188	188
cell adhesion mediated by integrin	0.014	0.074	0.5	7	-10000	0	7
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.17	0.21	-10000	0	-0.43	193	193
RAC1-CDC42/GTP	-0.2	0.21	-10000	0	-0.49	144	144
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.05	0.15	-10000	0	-0.48	4	4
ruffle organization	-0.11	0.22	-10000	0	-0.55	11	11
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.018	0.11	-10000	0	-0.45	24	24
Ephrin B/EPHB2/KALRN	-0.013	0.067	-10000	0	-0.46	10	10
ROCK1	-0.073	0.08	-10000	0	-10000	0	0
RAS family/GDP	-0.081	0.11	-10000	0	-0.52	3	3
Rac1/GTP	-0.16	0.2	-10000	0	-0.58	11	11
Ephrin B/EPHB1/Src/Paxillin	-0.11	0.18	-10000	0	-0.33	191	191

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.082	0.062	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.14	0.18	-9999	-0.65	43	43
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.6	72	72
Syndecan-4/ADAM12	-0.17	0.18	-9999	-0.64	45	45
CCL5	-0.047	0.21	-9999	-0.69	42	42
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	-0.002	0.038	-9999	-0.29	8	8
ADAM12	-0.067	0.14	-9999	-0.31	123	123
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	-0.063	0.043	-9999	-0.23	5	5
Syndecan-4/Laminin alpha1	-0.17	0.21	-9999	-0.68	52	52
Syndecan-4/CXCL12/CXCR4	-0.17	0.23	-9999	-0.65	72	72
Syndecan-4/Laminin alpha3	-0.16	0.2	-9999	-0.66	48	48
MDK	-0.087	0.15	-9999	-0.31	152	152
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.64	45	45
Syndecan-4/Midkine	-0.18	0.2	-9999	-0.66	45	45
FZD7	0.007	0.074	-9999	-0.81	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.6	44	44
THBS1	-0.017	0.095	-9999	-0.31	47	47
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.66	44	44
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.6	72	72
Syndecan-4/TACI	-0.25	0.26	-9999	-0.63	134	134
CXCR4	0.011	0.025	-9999	-0.31	3	3
cell adhesion	-0.063	0.09	-9999	-0.44	19	19
Syndecan-4/Dynamin	-0.14	0.18	-9999	-0.65	43	43
Syndecan-4/TSP1	-0.15	0.18	-9999	-0.65	44	44
Syndecan-4/GIPC	-0.14	0.18	-9999	-0.65	43	43
Syndecan-4/RANTES	-0.17	0.22	-9999	-0.74	52	52
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.048	0.22	-9999	-0.8	37	37
LAMA3	-0.025	0.16	-9999	-0.58	32	32
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.022	0.15	-9999	-0.73	19	19
Syndecan-4/alpha-Actinin	-0.14	0.18	-9999	-0.65	43	43
TFPI	-0.034	0.19	-9999	-0.81	28	28
F2	-0.007	0.052	-9999	-0.31	14	14
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.17	0.21	-9999	-0.66	57	57
ACTN1	0.013	0.015	-9999	-0.31	1	1
TNC	-0.11	0.17	-9999	-0.32	181	181
Syndecan-4/CXCL12	-0.18	0.24	-9999	-0.68	72	72
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.074	0.25	-9999	-0.81	52	52
TNFRSF13B	-0.2	0.36	-9999	-0.79	131	131
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.012	0.037	-9999	-0.81	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.66	43	43
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	354	354
cell migration	-0.021	0.016	-9999	-10000	0	0
PRKCD	0.008	0.014	-9999	-10000	0	0
vasculogenesis	-0.14	0.18	-9999	-0.62	44	44
SDC4	-0.15	0.19	-9999	-0.7	43	43
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.69	44	44
Syndecan-4/PI-4-5-P2/PKC alpha	-0.05	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.14	0.18	-9999	-0.65	43	43
MMP9	-0.085	0.24	-9999	-0.58	80	80
Rac1/GTP	-0.07	0.087	-9999	-0.46	19	19
cytoskeleton organization	-0.13	0.17	-9999	-0.62	43	43
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.21	-9999	-0.64	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	0.046	-9999	-1	1	1
forebrain development	-0.31	0.28	-9999	-0.55	256	256
GNAO1	-0.02	0.15	-9999	-0.7	21	21
SMO/beta Arrestin2	0.011	0.031	-9999	-0.62	1	1
SMO	0.006	0.038	-9999	-0.81	1	1
ARRB2	0.008	0.007	-9999	-10000	0	0
GLI3/SPOP	0.044	0.056	-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	0.029	-9999	-0.49	1	1
GNAI1	0.008	0.038	-9999	-0.82	1	1
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.24	0.19	-9999	-0.51	135	135
SAP30	0.013	0.037	-9999	-0.81	1	1
mol:GDP	0.006	0.038	-9999	-0.81	1	1
MIM/GLI2A	-0.007	0.043	-9999	-0.3	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GLI2	0.033	0.061	-9999	-10000	0	0
GLI3	0.039	0.058	-9999	-0.3	14	14
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	0.037	-9999	-0.81	1	1
Gi family/GTP	0.008	0.07	-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)	0.023	0.058	-9999	-10000	0	0
FOXA2	-0.66	0.66	-9999	-1.3	239	239
neural tube patterning	-0.31	0.28	-9999	-0.55	256	256
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	-0.3	1	1
embryonic limb morphogenesis	-0.31	0.28	-9999	-0.55	256	256
SUFU	0.016	0.021	-9999	-0.28	1	1
LGALS3	-0.09	0.15	-9999	-0.31	157	157
catabolic process	0.061	0.068	-9999	-0.39	2	2
GLI3A/CBP	-0.19	0.2	-9999	-0.38	255	255
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.32	0.29	-9999	-0.57	256	256
RAB23	0.007	0.074	-9999	-0.81	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	-0.029	0.079	-9999	-0.44	2	2
GNAZ	0.01	0.006	-9999	-10000	0	0
RBBP4	0.009	0.064	-9999	-0.81	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	0.057	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.013	0.062	-9999	-0.27	18	18
PTCH1	-0.28	0.27	-9999	-0.62	136	136
MIM/GLI1	-0.45	0.39	-9999	-0.75	257	257
CREBBP	-0.19	0.2	-9999	-0.38	255	255
Su(fu)/SIN3/HDAC complex	0.055	0.026	-9999	-10000	0	0

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.042	0.12	-9999	-0.45	29	29
alphaM/beta2 Integrin/GPIbA	-0.053	0.14	-9999	-0.49	38	38
alphaM/beta2 Integrin/proMMP-9	-0.092	0.2	-9999	-0.55	65	65
PLAUR	-0.089	0.15	-9999	-0.31	156	156
HMGB1	0.003	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.033	0.098	-9999	-0.42	21	21
AGER	-0.057	0.22	-9999	-0.78	38	38
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.01	0.083	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.11	0.19	-9999	-0.53	63	63
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.58	80	80
CYR61	-0.24	0.38	-9999	-0.81	150	150
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.068	0.088	-9999	-0.41	10	10
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.002	0.1	-9999	-0.58	13	13
MYH2	-0.099	0.11	-9999	-0.39	36	36
MST1R	0.001	0.095	-9999	-0.61	10	10
leukocyte activation during inflammatory response	-0.039	0.092	-9999	-0.41	14	14
APOB	-0.011	0.079	-9999	-0.31	32	32
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	-0.63	11	11
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	-0.019	0.15	-9999	-0.61	25	25
alphaM/beta2 Integrin/CTGF	-0.12	0.22	-9999	-0.56	93	93
alphaM/beta2 Integrin	-0.091	0.11	-9999	-0.34	48	48
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.064	0.14	-9999	-0.31	119	119
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.09	0.11	-9999	-0.33	48	48
cell adhesion	-0.053	0.14	-9999	-0.48	38	38
NFKB1	-0.12	0.29	-9999	-0.71	64	64
THY1	0.011	0.029	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.014	0.049	-9999	-0.33	2	2
alphaM/beta2 Integrin/LRP/tPA	-0.033	0.1	-9999	-0.48	15	15
IL6	-0.21	0.44	-9999	-1.1	94	94
ITGB2	-0.018	0.086	-9999	-0.33	30	30
elevation of cytosolic calcium ion concentration	-0.14	0.16	-9999	-0.5	39	39
alphaM/beta2 Integrin/JAM2/JAM3	-0.031	0.099	-9999	-0.48	15	15
JAM2	0.006	0.076	-9999	-0.71	5	5
alphaM/beta2 Integrin/ICAM1	-0.059	0.12	-9999	-0.49	22	22
alphaM/beta2 Integrin/uPA/Plg	-0.097	0.12	-9999	-0.5	21	21
RhoA/GTP	-0.1	0.12	-9999	-0.4	41	41
positive regulation of phagocytosis	-0.067	0.12	-9999	-0.46	20	20
Ron/MSP	-0.011	0.076	-9999	-0.62	7	7
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.16	-9999	-0.51	39	39
alphaM/beta2 Integrin/uPAR	-0.083	0.13	-9999	-0.45	35	35
PLAU	-0.14	0.16	-9999	-0.31	230	230
PLAT	0.003	0.076	-9999	-0.45	11	11
actin filament polymerization	-0.095	0.11	-9999	-0.37	37	37
MST1	0.011	0.04	-9999	-0.56	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.039	0.093	-9999	-0.42	14	14
TNF	-0.17	0.39	-9999	-0.97	79	79
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.13	-9999	-0.43	39	39
fibrinolysis	-0.097	0.12	-9999	-0.5	21	21
HCK	-0.01	0.084	-9999	-0.31	36	36
dendritic cell antigen processing and presentation	-0.09	0.11	-9999	-0.33	48	48
VTN	-0.067	0.24	-9999	-0.75	52	52
alphaM/beta2 Integrin/CYR61	-0.2	0.27	-9999	-0.57	164	164
LPA	-0.002	0.042	-9999	-0.31	9	9
LRP1	0.012	0.037	-9999	-0.81	1	1
cell migration	-0.089	0.2	-9999	-0.57	60	60
FN1	-0.22	0.14	-9999	-0.31	359	359
alphaM/beta2 Integrin/Thy1	-0.034	0.099	-9999	-0.41	22	22
MPO	0	0.094	-9999	-0.65	9	9
KNG1	-0.014	0.078	-9999	-0.31	32	32
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.09	0.11	-9999	-0.38	38	38
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.039	-9999	-0.31	8	8
CTGF	-0.11	0.3	-9999	-0.81	76	76
alphaM/beta2 Integrin/Hck	-0.045	0.12	-9999	-0.45	35	35
ITGAM	-0.022	0.11	-9999	-0.38	32	32
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.046	0.13	-9999	-0.52	26	26
HP	-0.082	0.16	-9999	-0.33	135	135
leukocyte adhesion	-0.087	0.16	-9999	-0.59	27	27
SELP	-0.002	0.1	-9999	-0.58	13	13

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.38	-9999	-1.3	40	40
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.033	0.11	-9999	-0.39	20	20
ATF2/c-Jun	-0.22	0.42	-9999	-0.97	113	113
MAPK11	-0.033	0.11	-9999	-0.39	20	20
MITF	-0.026	0.13	-9999	-0.41	40	40
MAPKAPK5	-0.026	0.13	-9999	-0.41	40	40
KRT8	-0.026	0.13	-9999	-0.41	40	40
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.044	0.16	-9999	-0.52	40	40
CEBPB	-0.026	0.13	-9999	-0.41	40	40
SLC9A1	-0.026	0.13	-9999	-0.41	40	40
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.071	0.19	-9999	-0.56	40	40
p38alpha-beta/MNK1	-0.022	0.13	-9999	-0.49	20	20
JUN	-0.22	0.42	-9999	-0.96	113	113
PPARGC1A	-0.23	0.25	-9999	-0.45	258	258
USF1	-0.026	0.13	-9999	-0.41	40	40
RAB5/GDP/GDI1	-0.036	0.082	-9999	-0.35	20	20
NOS2	-0.045	0.16	-9999	-0.54	20	20
DDIT3	-0.028	0.13	-9999	-0.41	40	40
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.01	0.11	-9999	-0.39	20	20
p38alpha-beta/HBP1	-0.022	0.13	-9999	-0.49	20	20
CREB1	-0.046	0.15	-9999	-0.46	40	40
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.012	0.12	-9999	-0.43	20	20
RPS6KA4	-0.026	0.13	-9999	-0.41	40	40
PLA2G4A	-0.045	0.19	-9999	-0.58	45	45
GDI1	-0.026	0.13	-9999	-0.41	40	40
TP53	-0.034	0.16	-9999	-0.51	40	40
RPS6KA5	-0.075	0.2	-9999	-0.46	87	87
ESR1	-0.06	0.2	-9999	-0.54	55	55
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.027	0.13	-9999	-0.41	41	41
MEF2A	-0.027	0.13	-9999	-0.41	41	41
EIF4EBP1	-0.046	0.15	-9999	-0.46	41	41
KRT19	-0.1	0.2	-9999	-0.53	57	57
ELK4	-0.026	0.13	-9999	-0.41	40	40
ATF6	-0.026	0.13	-9999	-0.41	40	40
ATF1	-0.047	0.16	-9999	-0.47	41	41
p38alpha-beta/MAPKAPK2	-0.022	0.13	-9999	-0.49	20	20
p38alpha-beta/MAPKAPK3	-0.022	0.13	-9999	-0.49	20	20

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.049	0.21	-10000	0	-0.64	25	25
CRP	-0.054	0.21	-10000	0	-0.71	16	16
cell cycle arrest	-0.07	0.23	-10000	0	-0.72	30	30
TIMP1	-0.15	0.21	-10000	0	-0.6	37	37
IL6ST	-0.11	0.29	-10000	0	-0.81	72	72
Rac1/GDP	-0.078	0.24	-10000	0	-0.58	62	62
AP1	-0.19	0.32	-10000	0	-0.66	137	137
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.09	0.22	-10000	0	-0.68	21	21
HSP90B1	0.024	0.042	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
MAPK14	-0.085	0.29	-10000	0	-0.77	56	56
AKT1	0.053	0.056	-10000	0	-1.1	1	1
FOXO1	0.059	0.053	-10000	0	-0.98	1	1
MAP2K6	-0.091	0.28	-10000	0	-0.65	71	71
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.067	0.23	-10000	0	-0.63	44	44
MITF	-0.079	0.25	-10000	0	-0.55	75	75
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	0.024	0.006	-10000	0	-10000	0	0
CEBPB	0.022	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.019	0.085	-10000	0	-0.49	1	1
STAT3	-0.082	0.24	-10000	0	-0.78	30	30
STAT1	-0.01	0.022	-10000	0	-10000	0	0
CEBPD	-0.049	0.21	-10000	0	-0.69	16	16
PIK3CA	0.01	0.064	-10000	0	-0.81	3	3
PI3K	0.019	0.05	-10000	0	-0.62	3	3
JUN	-0.18	0.35	-10000	0	-0.81	112	112
PIAS3/MITF	-0.067	0.24	-10000	0	-0.61	52	52
MAPK11	-0.085	0.29	-10000	0	-0.77	56	56
STAT3 (dimer)/FOXO1	-0.001	0.2	-10000	0	-0.58	19	19
GRB2/SOS1/GAB family	-0.11	0.19	-10000	0	-0.68	31	31
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.11	0.25	-10000	0	-0.44	147	147
GRB2	0.014	0	-10000	0	-10000	0	0
JAK2	0.01	0.053	-10000	0	-0.81	2	2
LBP	-0.055	0.19	-10000	0	-0.61	14	14
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.014	0.004	-10000	0	-10000	0	0
MYC	-0.063	0.26	-10000	0	-0.87	27	27
FGG	-0.058	0.21	-10000	0	-0.69	19	19
macrophage differentiation	-0.07	0.23	-10000	0	-0.72	30	30
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.17	0.28	-10000	0	-0.56	147	147
JUNB	-0.055	0.23	-10000	0	-0.73	27	27
FOS	-0.2	0.36	-10000	0	-0.81	127	127
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.089	0.27	-10000	0	-0.46	137	137
STAT1/PIAS1	-0.072	0.23	-10000	0	-0.55	60	60
GRB2/SOS1/GAB family/SHP2/PI3K	0.039	0.06	-10000	0	-0.59	3	3
STAT3 (dimer)	-0.079	0.24	-10000	0	-0.76	30	30
PRKCD	-0.055	0.22	-10000	0	-0.62	38	38
IL6R	-0.014	0.15	-10000	0	-0.81	17	17
SOCS3	-0.097	0.35	-10000	0	-1	49	49
gp130 (dimer)/JAK1/JAK1/LMO4	-0.058	0.2	-10000	0	-0.54	72	72
Rac1/GTP	-0.088	0.24	-10000	0	-0.59	61	61
HCK	-0.011	0.084	-10000	0	-0.31	36	36
MAPKKK cascade	0.012	0.076	-10000	0	-0.98	1	1
bone resorption	-0.085	0.21	-10000	0	-0.63	24	24
IRF1	-0.049	0.21	-10000	0	-0.64	24	24
mol:GDP	-0.09	0.25	-10000	0	-0.59	68	68
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.092	0.26	-10000	0	-0.61	68	68
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.097	0.29	-10000	0	-0.79	54	54
PTPN11	-0.01	0.058	-10000	0	-1.2	1	1
IL6/IL6RA	-0.13	0.27	-10000	0	-0.65	99	99
gp130 (dimer)/TYK2/TYK2/LMO4	-0.064	0.2	-10000	0	-0.54	72	72
gp130 (dimer)/JAK2/JAK2/LMO4	-0.066	0.2	-10000	0	-0.55	72	72
IL6	-0.15	0.32	-10000	0	-0.69	116	116
PIAS3	0.013	0	-10000	0	-10000	0	0
PTPRE	-0.087	0.15	-10000	0	-0.31	148	148
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	-0.093	0.26	-10000	0	-0.46	131	131
LMO4	0.013	0.009	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.097	0.23	0.38	1	-0.77	30	31
MCL1	0.059	0.048	-10000	0	-0.88	1	1

×

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	0.005	0.083	-9999	-0.81	5	5
EGF/EGFR	-0.078	0.17	-9999	-0.45	83	83
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.073	0.17	-9999	-0.46	77	77
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.009	0.047	-9999	-0.41	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	78	78
EGF/EGFR dimer/SHC	-0.086	0.2	-9999	-0.54	77	77
mol:GDP	-0.072	0.16	-9999	-0.45	77	77
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.003	0.086	-9999	-0.62	8	8
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.066	0.15	-9999	-0.42	77	77
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.067	0.15	-9999	-0.42	77	77
FRAP1	-0.036	0.17	-9999	-0.44	77	77
EGF/EGFR dimer	-0.1	0.23	-9999	-0.62	77	77
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	-0.59	7	7

×

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	-0.033	0.11	-10000	0	-0.31	69	69
GNB1/GNG2	-0.042	0.067	-10000	0	-0.2	44	44
AKT1	-0.007	0.1	-10000	0	-0.2	70	70
EGF	-0.11	0.29	-10000	0	-0.78	78	78
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.033	0.07	-10000	0	-0.71	1	1
mol:Ca2+	-0.035	0.14	-10000	0	-0.31	73	73
LYN	0.034	0.07	-10000	0	-0.71	1	1
RhoA/GTP	-0.029	0.045	-10000	0	-0.14	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.034	0.16	-10000	0	-0.34	72	72
GNG2	0.012	0.037	-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	-0.55	12	12
G beta5/gamma2	-0.056	0.091	-10000	0	-0.27	45	45
PRKCH	-0.042	0.16	-10000	0	-0.36	72	72
DNM1	-0.014	0.15	-10000	0	-0.78	17	17
TXA2/TP beta/beta Arrestin3	-0.012	0.054	-10000	0	-0.3	16	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.02	0.16	-10000	0	-0.81	20	20
G12 family/GTP	-0.072	0.11	-10000	0	-0.31	70	70
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	0.012	0.1	0.34	14	-10000	0	14
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.22	0.37	-10000	0	-0.81	137	137
mol:IP3	-0.05	0.18	-10000	0	-0.38	73	73
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.075	0.23	-10000	0	-0.53	72	72
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.094	0.2	-10000	0	-0.38	145	145
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.025	0.076	-10000	0	-0.71	1	1
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.005	0.083	-10000	0	-0.81	5	5
PRKCB1	-0.05	0.17	-10000	0	-0.38	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	-0.072	0.23	-10000	0	-0.54	73	73
LCK	0.024	0.091	-10000	0	-0.54	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.017	0.081	-10000	0	-1.1	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.029	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.017	0.08	-10000	0	-1.1	1	1
MAPK14	-0.012	0.11	-10000	0	-0.23	70	70
TGM2/GTP	-0.062	0.2	-10000	0	-0.43	74	74
MAPK11	-0.012	0.11	-10000	0	-0.23	70	70
ARHGEF1	-0.01	0.088	-10000	0	-0.18	29	29
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.046	0.18	-10000	0	-0.39	73	73
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.04	0.15	-10000	0	-0.3	79	79
cAMP biosynthetic process	-0.05	0.16	-10000	0	-0.36	74	74
Gq family/GTP/EBP50	-0.045	0.12	-10000	0	-0.35	23	23
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.034	0.07	-10000	0	-0.71	1	1
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	-0.3	15	15
VCAM1	-0.029	0.14	-10000	0	-0.3	74	74
TP beta/Gq family/GDP/G beta5/gamma2	-0.026	0.12	-10000	0	-0.55	12	12
platelet activation	-0.017	0.15	-10000	0	-0.3	70	70
PGI2/IP	-0.006	0.063	-10000	0	-0.63	5	5
PRKACA	0.002	0.095	-10000	0	-0.4	24	24
Gq family/GDP/G beta5/gamma2	-0.028	0.12	-10000	0	-0.5	12	12
TXA2/TP beta/beta Arrestin2	-0.023	0.12	-10000	0	-0.66	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.009	0.1	-10000	0	-0.39	24	24
mol:DAG	-0.057	0.19	-10000	0	-0.43	73	73
EGFR	0.005	0.083	-10000	0	-0.81	5	5
TXA2/TP alpha	-0.071	0.22	-10000	0	-0.49	73	73
Gq family/GTP	-0.077	0.13	-10000	0	-0.3	125	125
YES1	0.034	0.07	-10000	0	-0.71	1	1
GNAI2/GTP	-0.015	0.07	-10000	0	-0.9	1	1
PGD2/DP	-0.026	0.12	-10000	0	-0.63	20	20
SLC9A3R1	0.012	0.021	-10000	0	-0.31	2	2
FYN	0.034	0.07	-10000	0	-0.71	1	1
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.011	0.09	-10000	0	-0.32	36	36
PGK/cGMP	-0.15	0.24	-10000	0	-0.55	137	137
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.029	0.092	-10000	0	-0.6	5	5
NOS3	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.052	0.18	-10000	0	-0.38	80	80
PRKCB	-0.051	0.17	-10000	0	-0.38	75	75
PRKCE	-0.045	0.17	-10000	0	-0.37	74	74
PRKCD	-0.045	0.17	-10000	0	-0.38	72	72
PRKCG	-0.049	0.17	-10000	0	-0.39	74	74
muscle contraction	-0.062	0.22	-10000	0	-0.49	73	73
PRKCZ	-0.034	0.16	-10000	0	-0.34	72	72
ARR3	0.004	0.006	-10000	0	-10000	0	0
TXA2/TP beta	-0.017	0.081	-10000	0	-1.1	1	1
PRKCQ	-0.044	0.17	-10000	0	-0.36	78	78
MAPKKK cascade	-0.063	0.2	-10000	0	-0.47	73	73
SELE	-0.049	0.18	-10000	0	-0.43	72	72
TP beta/GNAI2/GDP/G beta/gamma	-0.017	0.086	-10000	0	-1.3	1	1
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.35	-10000	0	-0.81	118	118
chemotaxis	-0.083	0.26	-10000	0	-0.62	73	73
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	-0.003	0.12	-10000	0	-0.81	10	10
Rac1/GTP	0.004	0.005	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.025	0.077	0.29	36	-10000	0	36
RFC1	0.025	0.077	0.29	36	-10000	0	36
PRKDC	0.025	0.077	0.29	36	-10000	0	36
RIPK1	0.014	0.004	-10000	0	-10000	0	0
CASP7	-0.012	0.045	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.029	0.1	0.26	5	-0.37	37	42
MAP2K4	-0.02	0.16	-10000	0	-0.4	39	39
mol:ceramide	-0.022	0.15	-10000	0	-0.47	38	38
GSN	0.025	0.077	0.29	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 8	-0.02	0.14	-10000	0	-0.46	37	37
FAS	0.011	0.006	-10000	0	-10000	0	0
BID	-0.028	0.077	0.32	3	-10000	0	3
MAP3K1	0.006	0.097	-10000	0	-0.28	16	16
MAP3K7	0.011	0.005	-10000	0	-10000	0	0
RB1	0.024	0.078	0.29	35	-0.31	1	36
CFLAR	0.014	0.004	-10000	0	-10000	0	0
HGF/MET	-0.14	0.22	-10000	0	-0.61	77	77
ARHGDIB	0.022	0.08	0.29	36	-10000	0	36
FADD	0.011	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.025	0.077	-10000	0	-0.29	36	36
NFKB1	-0.049	0.09	-10000	0	-0.32	17	17
MAPK8	-0.052	0.21	-10000	0	-0.44	95	95
DFFA	0.025	0.077	0.29	36	-10000	0	36
DNA fragmentation during apoptosis	0.025	0.077	0.29	36	-10000	0	36
FAS/FADD/MET	-0.057	0.075	-10000	0	-10000	0	0
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.003	0.089	-10000	0	-0.38	22	22
FAF1	0.011	0.006	-10000	0	-10000	0	0
PARP1	0.025	0.077	0.29	36	-10000	0	36
DFFB	0.025	0.077	0.29	36	-10000	0	36
CHUK	-0.042	0.08	-10000	0	-0.73	1	1
FASLG	-0.064	0.23	-10000	0	-0.66	55	55
FAS/FADD	-0.001	0.001	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.81	74	74
LMNA	0.023	0.07	0.26	36	-10000	0	36
CASP6	0.025	0.077	0.29	36	-10000	0	36
CASP10	0.011	0.006	-10000	0	-10000	0	0
CASP3	0.03	0.094	0.34	39	-10000	0	39
PTPN13	0.003	0.091	-10000	0	-0.81	6	6
CASP8	0.008	0.045	0.45	3	-10000	0	3
IL6	-0.23	0.54	-10000	0	-1.4	88	88
MET	-0.1	0.16	-10000	0	-0.31	179	179
ICAD/CAD	0.023	0.072	0.27	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 10	-0.022	0.15	-10000	0	-0.48	38	38
activation of caspase activity by cytochrome c	-0.028	0.077	0.32	3	-10000	0	3
PAK2	0.025	0.077	0.29	36	-10000	0	36
BCL2	-0.047	0.22	-10000	0	-0.81	36	36

×

TCGA08_p53

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
CDKN2A	-0.08	0.11	-9999	-0.21	204	204
TP53	-0.027	0.032	-9999	-10000	0	0
Senescence	-0.027	0.032	-9999	-10000	0	0
Apoptosis	-0.027	0.032	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.051	0.061	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.072	0.096	-10000	0	-10000	0	0
CRKL	-0.03	0.11	-10000	0	-0.33	25	25
mol:PIP3	-0.019	0.032	0.68	1	-10000	0	1
AKT1	0.001	0.039	0.45	1	-0.53	2	3
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	-0.021	0.11	-10000	0	-0.3	25	25
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
HGF/MET/SHIP2	-0.14	0.2	-10000	0	-0.59	74	74
MAP3K5	-0.018	0.11	-10000	0	-0.47	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.19	-10000	0	-0.54	74	74
AP1	-0.27	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	-0.26	0.4	-10000	0	-0.86	151	151
STAT3 (dimer)	-0.038	0.13	-10000	0	-0.33	74	74
GAB1/CRKL/SHP2/PI3K	-0.042	0.093	-10000	0	-0.69	2	2
INPP5D	-0.003	0.071	-10000	0	-0.31	25	25
CBL/CRK	-0.021	0.11	-10000	0	-10000	0	0
PTPN11	0.012	0.037	-10000	0	-0.81	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.037	-10000	0	-0.81	1	1
ELK1	-0.047	0.061	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.039	0.071	-10000	0	-0.24	26	26
PAK1	0.009	0.037	0.42	1	-0.49	2	3
HGF/MET/RANBP10	-0.14	0.2	-10000	0	-0.59	74	74
HRAS	-0.057	0.16	-10000	0	-0.42	74	74
DOCK1	-0.025	0.12	-10000	0	-0.55	4	4
GAB1	-0.04	0.12	-10000	0	-0.3	74	74
CRK	-0.03	0.11	-10000	0	-0.33	25	25
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.11	0.21	-10000	0	-0.6	74	74
JUN	-0.17	0.35	-10000	0	-0.81	112	112
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.07	0.1	-10000	0	-0.29	74	74
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.011	0.14	-10000	0	-0.64	2	2
GRB2/SHC	-0.037	0.096	-10000	0	-0.3	25	25
FOS	-0.2	0.36	-10000	0	-0.81	127	127
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.047	0.061	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.14	0.21	-10000	0	-0.6	74	74
cell migration	-0.037	0.094	-10000	0	-0.29	25	25
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.072	0.096	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.05	0.14	-10000	0	-0.36	74	74
MET/MUC20	-0.076	0.1	-10000	0	-0.21	179	179
RAP1B	-0.012	0.1	-10000	0	-10000	0	0
RAP1A	-0.012	0.1	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.14	0.2	-10000	0	-0.59	74	74
RAF1	-0.047	0.15	-10000	0	-0.45	26	26
STAT3	-0.039	0.13	-10000	0	-0.39	25	25
cell proliferation	-0.046	0.17	-10000	0	-0.45	74	74
RPS6KB1	-0.015	0.039	-10000	0	-10000	0	0
MAPK3	-0.049	0.056	-10000	0	-10000	0	0
MAPK1	-0.049	0.056	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.008	0.14	-10000	0	-0.57	15	15
SRC	-0.039	0.13	-10000	0	-0.38	25	25
PI3K	-0.04	0.1	-10000	0	-0.32	28	28
MET/Glomulin	-0.056	0.092	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.036	0.14	-10000	0	-0.41	26	26
MET	-0.1	0.16	-10000	0	-0.31	179	179
MAP4K1	-0.027	0.12	-10000	0	-0.33	29	29
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.036	0.14	-10000	0	-0.41	26	26
BAD	0.009	0.037	0.42	1	-0.49	2	3
MAP2K4	-0.009	0.1	-10000	0	-0.42	5	5
SHP2/GRB2/SOS1/GAB1	-0.056	0.09	-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	-0.048	0.1	-10000	0	-0.32	25	25
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.81	74	74
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	-0.04	0.11	-10000	0	-0.27	74	74
PDPK1	-0.009	0.043	0.51	1	-0.57	2	3
HGF/MET/SHIP	-0.14	0.2	-10000	0	-0.59	74	74

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.013	0.014	-9999	-10000	0	0
REL	-0.036	0.21	-9999	-0.81	33	33
HDAC7	-0.034	0.15	-9999	-0.64	17	17
JUN	-0.18	0.34	-9999	-0.81	112	112
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	0.097	-9999	-0.64	11	11
FOXO1	0.013	0.001	-9999	-10000	0	0
T-DHT/AR	-0.047	0.16	-9999	-0.66	19	19
MAP2K6	-0.01	0.12	-9999	-0.78	12	12
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	0.058	-9999	-10000	0	0
NCOA2	-0.074	0.24	-9999	-0.82	48	48
CEBPA	0.006	0.083	-9999	-0.81	5	5
EHMT2	0.009	0.006	-9999	-10000	0	0
cell proliferation	-0.07	0.15	-9999	-0.55	17	17
NR0B1	-0.002	0.04	-9999	-0.31	8	8
EGR1	-0.17	0.34	-9999	-0.82	107	107
RXRs/9cRA	-0.13	0.058	-9999	-0.5	4	4
AR/RACK1/Src	-0.12	0.16	-9999	-0.67	19	19
AR/GR	-0.13	0.2	-9999	-0.36	163	163
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	-0.002	0.097	-9999	-0.63	11	11
T-DHT/AR/TIF2/CARM1	-0.13	0.24	-9999	-0.69	56	56
SRC	-0.005	0.12	-9999	-0.55	19	19
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.4	0.57	-9999	-1.3	142	142
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.056	0.15	-9999	-0.67	19	19
TMPRSS2	-0.059	0.31	-9999	-1.2	32	32
RXRG	-0.28	0.11	-9999	-0.32	437	437
mol:9cRA	-0.002	0.003	-9999	-10000	0	0
RXRA	0.013	0.001	-9999	-10000	0	0
RXRB	0.013	0.001	-9999	-10000	0	0
CARM1	0.007	0.007	-9999	-10000	0	0
NR2C2	-0.006	0.12	-9999	-0.81	11	11
KLK2	-0.48	0.42	-9999	-0.82	291	291
AR	-0.15	0.22	-9999	-0.38	214	214
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	-0.013	0.05	-9999	-0.32	11	11
T-DHT/AR/RACK1/Src	-0.079	0.15	-9999	-0.66	19	19
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	-0.027	0.1	-9999	-0.32	54	54
T-DHT/AR/TIF2	-0.057	0.16	-9999	-0.46	50	50
T-DHT/AR/Hsp90	-0.058	0.15	-9999	-0.67	19	19
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.008	0.12	-9999	-0.59	19	19
SIRT1	0.011	0.037	-9999	-0.81	1	1
ZMIZ2	0.023	0.015	-9999	-10000	0	0
POU2F1	0.031	0.019	-9999	-0.3	1	1
T-DHT/AR/DAX-1	-0.076	0.14	-9999	-0.68	19	19
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.009	0.007	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.11	0.1	-9999	-0.64	7	7
EPHB2	0.008	0.064	-9999	-0.81	3	3
Syndecan-2/TACI	-0.13	0.25	-9999	-0.56	128	128
LAMA1	-0.048	0.22	-9999	-0.8	37	37
Syndecan-2/alpha2 ITGB1	-0.071	0.11	-9999	-0.46	24	24
HRAS	0.012	0.021	-9999	-0.31	2	2
Syndecan-2/CASK	-0.008	0.064	-9999	-0.54	7	7
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.023	0.1	-9999	-0.5	18	18
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.007	0.058	-9999	-0.49	7	7
LAMA3	-0.025	0.16	-9999	-0.58	32	32
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.064	-9999	-0.81	3	3
Syndecan-2/MMP2	0.008	0.1	-9999	-0.57	13	13
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.078	0.097	-9999	-10000	0	0
dendrite morphogenesis	0.014	0.079	-9999	-0.54	10	10
Syndecan-2/GM-CSF	-0.11	0.097	-9999	-0.56	7	7
determination of left/right symmetry	0.012	0.076	-9999	-0.62	7	7
Syndecan-2/PKC delta	0.018	0.066	-9999	-0.54	7	7
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.086	0.09	-9999	-0.51	7	7
MAPK1	-0.086	0.09	-9999	-0.51	7	7
Syndecan-2/RACK1	-0.007	0.055	-9999	-0.46	7	7
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.076	-9999	-0.62	7	7
ITGA2	-0.11	0.16	-9999	-0.31	193	193
MAPK8	0.015	0.11	-9999	-0.55	18	18
Syndecan-2/alpha2/beta1 Integrin	-0.084	0.14	-9999	-0.51	40	40
Syndecan-2/Kininogen	-0.007	0.077	-9999	-0.54	7	7
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.031	0.057	-9999	-0.43	7	7
Syndecan-2/CASK/Protein 4.1	-0.007	0.058	-9999	-0.5	7	7
extracellular matrix organization	0.015	0.07	-9999	-0.53	7	7
actin cytoskeleton reorganization	-0.11	0.1	-9999	-0.64	7	7
Syndecan-2/Caveolin-2/Ras	-0.01	0.075	-9999	-0.54	9	9
Syndecan-2/Laminin alpha3	-0.007	0.12	-9999	-0.54	24	24
Syndecan-2/RasGAP	-0.007	0.052	-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	0.079	-9999	-0.54	10	10
GO:0007205	0.004	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.056	-9999	-0.42	7	7
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.2	0.36	-9999	-0.79	131	131
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.078	0.097	-9999	-10000	0	0
Syndecan-2/Synbindin	0.018	0.066	-9999	-0.54	7	7
TGFB1	0.008	0.041	-9999	-0.31	8	8
CASP3	0.027	0.061	-9999	-0.48	7	7
FN1	-0.22	0.14	-9999	-0.31	359	359
Syndecan-2/IL8	-0.038	0.12	-9999	-0.54	18	18
SDC2	0.012	0.076	-9999	-0.62	7	7
KNG1	-0.014	0.078	-9999	-0.31	32	32
Syndecan-2/Neurofibromin	0.018	0.066	-9999	-0.54	7	7
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.21	0.15	-9999	-0.31	335	335
Syndecan-2/TGFB1	0.015	0.07	-9999	-0.54	7	7
Syndecan-2/Syntenin/PI-4-5-P2	-0.007	0.058	-9999	-0.5	7	7
Syndecan-2/Ezrin	-0.007	0.058	-9999	-0.49	7	7
PRKACA	0.027	0.061	-9999	-0.48	7	7
angiogenesis	-0.038	0.12	-9999	-0.54	18	18
MMP2	-0.001	0.1	-9999	-0.63	11	11
IL8	-0.082	0.18	-9999	-0.35	128	128
calcineurin-NFAT signaling pathway	-0.13	0.25	-9999	-0.55	128	128

×

Regulation of p38-alpha and p38-beta

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	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	-0.006	0.12	-9999	-0.77	12	12
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	286	286
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	0.029	-9999	-0.31	4	4
p38 alpha/TAB1	-0.048	0.068	-9999	-0.31	5	5
PRKG1	-0.22	0.37	-9999	-0.81	137	137
DUSP8	0.003	0.082	-9999	-0.51	10	10
PGK/cGMP/p38 alpha	-0.16	0.2	-9999	-0.46	140	140
apoptosis	-0.046	0.066	-9999	-0.3	5	5
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.12	0.3	-9999	-0.81	80	80
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.008	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.81	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	0.012	0.021	-9999	-0.31	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.061	0.13	-9999	-0.36	17	17
BLK	-0.24	0.37	-9999	-0.74	168	168
HCK	-0.01	0.084	-9999	-0.31	36	36
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.01	0.042	-9999	-0.48	3	3
TRAF6/MEKK3	-0.002	0.032	-9999	-0.5	2	2
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.028	0.092	-9999	-0.32	6	6
positive regulation of innate immune response	-0.059	0.14	-9999	-0.4	14	14
LCK	-0.01	0.11	-9999	-0.42	27	27
p38alpha-beta/MKP7	-0.05	0.13	-9999	-0.44	6	6
p38alpha-beta/MKP5	-0.051	0.13	-9999	-0.48	7	7
PGK/cGMP	-0.18	0.28	-9999	-0.63	137	137
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.12	0.2	-9999	-0.47	85	85
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	-0.81	286	286

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.011	0.041	-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	0.067	0.15	0.44	27	-10000	0	27
IL27/IL27R/JAK1	-0.12	0.19	-10000	0	-0.57	52	52
TBX21	-0.093	0.22	-10000	0	-0.62	38	38
IL12B	-0.006	0.098	-10000	0	-0.54	13	13
IL12A	-0.058	0.2	-10000	0	-0.61	54	54
IL6ST	-0.11	0.29	-10000	0	-0.82	72	72
IL27RA/JAK1	0.012	0.026	-10000	0	-10000	0	0
IL27	0.001	0.039	-10000	0	-0.32	7	7
TYK2	0.012	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.054	0.15	-10000	0	-0.51	1	1
T-helper 2 cell differentiation	0.067	0.15	0.44	27	-10000	0	27
T cell proliferation during immune response	0.067	0.15	0.44	27	-10000	0	27
MAPKKK cascade	-0.067	0.15	-10000	0	-0.44	27	27
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.05	-10000	0	-0.31	12	12
IL12RB1	-0.026	0.13	-10000	0	-0.37	48	48
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.091	0.21	-10000	0	-0.64	28	28
IL27/IL27R/JAK2/TYK2	-0.068	0.15	-10000	0	-0.44	27	27
positive regulation of T cell mediated cytotoxicity	-0.067	0.15	-10000	0	-0.44	27	27
STAT1 (dimer)	-0.12	0.24	0.52	16	-0.74	19	35
JAK2	0.011	0.054	-10000	0	-0.82	2	2
JAK1	0.014	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.056	0.14	-10000	0	-0.52	11	11
T cell proliferation	-0.15	0.23	-10000	0	-0.53	99	99
IL12/IL12R/TYK2/JAK2	-0.058	0.17	-10000	0	-0.72	15	15
IL17A	-0.054	0.15	-10000	0	-0.51	1	1
mast cell activation	0.067	0.15	0.44	27	-10000	0	27
IFNG	-0.021	0.048	-10000	0	-0.13	68	68
T cell differentiation	-0.005	0.008	-10000	0	-0.022	63	63
STAT3 (dimer)	-0.056	0.14	-10000	0	-0.52	11	11
STAT5A (dimer)	-0.056	0.14	-10000	0	-0.52	11	11
STAT4 (dimer)	-0.076	0.16	-10000	0	-0.52	25	25
STAT4	-0.025	0.14	-10000	0	-0.81	11	11
T cell activation	-0.012	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.063	0.19	-10000	0	-0.62	14	14
GATA3	-0.042	0.33	-10000	0	-1.5	25	25
IL18	-0.025	0.11	-10000	0	-0.57	13	13
positive regulation of mast cell cytokine production	-0.055	0.14	-10000	0	-0.51	11	11
IL27/EBI3	-0.099	0.12	-10000	0	-0.43	7	7
IL27RA	0.003	0.027	-10000	0	-10000	0	0
IL6	-0.15	0.32	-10000	0	-0.72	107	107
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.034	0.16	-10000	0	-0.57	39	39
EBI3	-0.15	0.16	-10000	0	-0.31	242	242
TNF	-0.067	0.21	-10000	0	-0.59	64	64

×

Visual signal transduction: Rods

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
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.016	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.011	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.018	0.07	-9999	-0.55	5	5
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.025	-9999	-0.31	3	3
GRK1	-0.066	0.24	-9999	-0.81	47	47
CNG Channel	-0.029	0.083	-9999	-0.51	9	9
mol:Na +	-0.023	0.081	-9999	-0.45	13	13
mol:ADP	-0.066	0.24	-9999	-0.81	47	47
RGS9-1/Gbeta5/R9AP	-0.088	0.2	-9999	-0.55	78	78
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.024	0.083	-9999	-0.46	13	13
CNGB1	-0.002	0.067	-9999	-0.31	22	22
RDH5	-0.2	0.16	-9999	-0.31	319	319
SAG	0.002	0.015	-9999	-0.31	1	1
mol:Ca2+	0.015	0.088	-9999	-0.48	5	5
Na + (4 Units)	-0.021	0.074	-9999	-0.44	8	8
RGS9	-0.072	0.25	-9999	-0.79	53	53
GNB1/GNGT1	-0.003	0.024	-9999	-10000	0	0
GNAT1/GDP	-0.077	0.18	-9999	-0.48	78	78
GUCY2D	-0.01	0.11	-9999	-0.43	26	26
GNGT1	-0.004	0.037	-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	0.072	-9999	-0.47	5	5
mol:11-cis-retinal	-0.2	0.15	-9999	-0.31	319	319
mol:cGMP	-0.016	0.07	-9999	-0.48	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.13	0.097	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0.001	0.09	-9999	-0.54	11	11
Metarhodopsin II	-0.049	0.15	-9999	-0.51	47	47
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.074	-9999	-0.5	9	9
RGS9BP	-0.037	0.2	-9999	-0.81	30	30
Metarhodopsin II/Transducin	0.011	0.015	-9999	-10000	0	0
GCAP Family/Ca ++	-0.005	0.043	-9999	-0.51	3	3
PDE6A/B	-0.012	0.047	-9999	-10000	0	0
mol:Pi	-0.087	0.2	-9999	-0.55	78	78
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.022	-9999	-10000	0	0
PDE6B	0.013	0	-9999	-10000	0	0
PDE6A	-0.008	0.076	-9999	-0.31	29	29
PDE6G	-0.017	0.11	-9999	-0.38	38	38
RHO	0.006	0.016	-9999	-0.31	1	1
PDE6	-0.089	0.18	-9999	-0.48	81	81
GUCA1A	0.004	0.032	-9999	-0.31	5	5
GC2/GCAP Family	-0.005	0.043	-9999	-0.51	3	3
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.008	0.066	-9999	-0.69	4	4

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.033	0.12	-10000	0	-0.5	25	25
ER alpha/Gai/GDP/Gbeta gamma	0.007	0.15	-10000	0	-0.47	35	35
AKT1	-0.014	0.2	-10000	0	-0.86	25	25
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.013	0.2	-10000	0	-0.87	25	25
mol:Ca2+	-0.1	0.23	-10000	0	-0.49	120	120
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.071	0.18	-10000	0	-0.58	53	53
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.19	0.81	25	-10000	0	25
RhoA/GTP	-0.025	0.087	-10000	0	-0.4	23	23
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.036	0.13	-10000	0	-0.58	23	23
regulation of stress fiber formation	-0.011	0.12	0.46	5	-10000	0	5
E2/ERA-ERB (dimer)	-0.039	0.13	-10000	0	-0.57	25	25
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.033	0.11	-10000	0	-0.5	23	23
pseudopodium formation	0.011	0.12	-10000	0	-0.46	5	5
E2/ER alpha (dimer)/PELP1	-0.036	0.12	-10000	0	-0.55	23	23
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.012	0.037	-10000	0	-0.81	1	1
GNAO1	-0.017	0.15	-10000	0	-0.69	21	21
HRAS	0.012	0.021	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.013	0.15	-10000	0	-0.59	24	24
E2/ER beta (dimer)	-0.004	0.049	-10000	0	-0.63	3	3
mol:GDP	-0.034	0.12	-10000	0	-0.56	25	25
mol:NADP	0.013	0.15	-10000	0	-0.59	24	24
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.11	0.24	-10000	0	-0.52	120	120
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.12	0.25	-10000	0	-0.53	120	120
PLCB2	-0.12	0.25	-10000	0	-0.54	119	119
IGF1	-0.18	0.35	-10000	0	-0.79	119	119
mol:L-citrulline	0.013	0.15	-10000	0	-0.59	24	24
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.026	0.14	-10000	0	-0.78	16	16
JNK cascade	-0.004	0.049	-10000	0	-0.63	3	3
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.008	0.064	-10000	0	-0.81	3	3
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.046	0.19	-10000	0	-0.52	55	55
Gq family/GDP/Gbeta gamma	-0.057	0.18	-10000	0	-0.68	12	12
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.021	0.08	-10000	0	-0.36	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.036	0.13	-10000	0	-0.58	23	23
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.043	0.14	-10000	0	-0.63	23	23
STRN	-0.04	0.2	-10000	0	-0.81	32	32
GNAL	-0.094	0.28	-10000	0	-0.81	64	64
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.016	0.044	-10000	0	-0.55	3	3
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.037	-10000	0	-0.81	1	1
HBEGF	-0.004	0.16	-10000	0	-0.52	29	29
cAMP biosynthetic process	-0.089	0.18	-10000	0	-0.48	85	85
SRC	0.015	0.14	-10000	0	-0.5	24	24
PI3K	-0.004	0.048	-10000	0	-0.62	3	3
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.029	0.11	-10000	0	-0.51	23	23
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-10000	0	-0.52	38	38
Gs family/GTP	-0.091	0.19	-10000	0	-0.48	85	85
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	0.014	0.14	-10000	0	-0.55	25	25
mol:DAG	-0.11	0.24	-10000	0	-0.52	120	120
Gs family/GDP/Gbeta gamma	-0.072	0.16	-10000	0	-0.51	27	27
MSN	0.01	0.12	-10000	0	-0.5	5	5
Gq family/GTP	-0.15	0.24	-10000	0	-0.57	119	119
mol:PI-3-4-5-P3	-0.011	0.19	-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	-0.014	0.14	0.55	25	-10000	0	25
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.031	0.12	-10000	0	-0.52	25	25
NOS3	0.012	0.16	-10000	0	-0.63	24	24
GNA11	-0.003	0.12	-10000	0	-0.81	10	10
MAPKKK cascade	-0.008	0.19	-10000	0	-0.54	53	53
E2/ER alpha (dimer)/PELP1/Src	-0.038	0.14	-10000	0	-0.62	23	23
ruffle organization	0.011	0.12	-10000	0	-0.46	5	5
ROCK2	0.001	0.14	-10000	0	-0.43	25	25
GNA14	-0.18	0.35	-10000	0	-0.81	118	118
GNA15	-0.011	0.09	-10000	0	-0.32	36	36
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.027	0.19	-10000	0	-0.48	63	63
MMP2	0.015	0.15	-10000	0	-0.67	11	11

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.089	0.22	-9999	-0.53	45	45
MAP3K8	-0.001	0.098	-9999	-0.82	7	7
FOS	-0.055	0.17	-9999	-0.5	35	35
PRKCA	-0.021	0.16	-9999	-0.82	19	19
PTPN7	-0.047	0.18	-9999	-0.46	61	61
HRAS	0.011	0.021	-9999	-0.31	2	2
PRKCB	-0.024	0.12	-9999	-0.37	46	46
NRAS	0.013	0.002	-9999	-10000	0	0
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.029	0.12	-9999	-0.51	19	19
MAP2K1	-0.017	0.14	-9999	-0.57	25	25
ELK1	0.008	0.01	-9999	-10000	0	0
BRAF	-0.039	0.12	-9999	-0.57	23	23
mol:GTP	-0.001	0.003	-9999	-0.006	126	126
MAPK1	-0.029	0.12	-9999	-0.51	19	19
RAF1	-0.039	0.12	-9999	-0.57	23	23
KRAS	0.013	0.002	-9999	-10000	0	0

×

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	-0.01	0.12	-9999	-0.63	2	2
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	-0.044	0.13	-9999	-0.4	54	54
JUN	0.004	0.097	-9999	-0.27	12	12
HRAS	0.012	0.021	-9999	-0.31	2	2
DOCK7	-0.013	0.14	-9999	-0.38	57	57
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.054	0.15	-9999	-0.48	54	54
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.022	0.062	-9999	-0.32	3	3
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.019	0.15	-9999	-0.44	54	54
RAF1	-0.001	0.12	-9999	-0.4	18	18
ErbB2/ErbB3/neuregulin 2	-0.067	0.17	-9999	-0.51	64	64
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.022	0.082	-9999	-0.29	6	6
mol:PI-3-4-5-P3	0	0.002	-9999	-10000	0	0
cell proliferation	-0.12	0.33	-9999	-0.68	116	116
FOS	-0.1	0.28	-9999	-0.51	151	151
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.044	0.13	-9999	-0.4	54	54
MAPK3	-0.08	0.26	-9999	-0.5	113	113
MAPK1	-0.08	0.26	-9999	-0.5	113	113
JAK2	-0.012	0.13	-9999	-0.38	56	56
NF2	-0.002	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.014	0.13	-9999	-0.37	54	54
NRG1	-0.065	0.24	-9999	-0.79	47	47
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.012	0.13	-9999	-0.35	64	64
MAPK9	-0.022	0.06	-9999	-0.26	2	2
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.007	0.12	-9999	-0.73	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)	0.002	0.006	-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	-0.031	0.086	-9999	-0.38	2	2
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.053	0.2	-9999	-0.38	115	115
myelination	0.01	0.11	-9999	-0.46	3	3
PPP3CB	-0.009	0.12	-9999	-0.36	28	28
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-9999	-0.64	2	2
NRG2	-0.079	0.26	-9999	-0.79	57	57
mol:GDP	-0.014	0.13	-9999	-0.37	54	54
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.004	0.13	-9999	-0.41	21	21
SRC	0.013	0.015	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.012	0.13	-9999	-0.38	55	55
MAP2K1	-0.072	0.23	-9999	-0.45	96	96
heart morphogenesis	-0.044	0.13	-9999	-0.4	54	54
RAS family/GDP	-0.005	0.11	-9999	-0.63	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.008	-9999	-10000	0	0
CHRNE	0.01	0.035	-9999	-0.13	18	18
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.044	0.13	-9999	-0.4	54	54
CDC42	0.013	0	-9999	-10000	0	0

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.031	0.14	-9999	-0.58	6	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.054	0.11	-9999	-0.61	3	3
alphaV/beta3 Integrin/Osteopontin/Src	-0.064	0.15	-9999	-0.61	25	25
AP1	-0.26	0.35	-9999	-0.85	110	110
ILK	-0.031	0.15	-9999	-0.61	6	6
bone resorption	-0.04	0.16	-9999	-0.64	11	11
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.051	0.12	-9999	-0.56	6	6
ITGAV	0.01	0.052	-9999	-0.81	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.032	0.14	-9999	-0.62	25	25
alphaV/beta3 Integrin/Osteopontin	-0.068	0.15	-9999	-0.54	39	39
MAP3K1	-0.031	0.15	-9999	-0.49	39	39
JUN	-0.17	0.35	-9999	-0.81	112	112
MAPK3	-0.031	0.14	-9999	-0.59	6	6
MAPK1	-0.031	0.14	-9999	-0.59	6	6
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.81	1	1
MAPK8	-0.031	0.17	-9999	-0.49	46	46
ITGB3	-0.011	0.14	-9999	-0.81	15	15
NFKBIA	-0.025	0.14	-9999	-0.61	5	5
FOS	-0.2	0.36	-9999	-0.81	127	127
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.11	0.17	-9999	-0.69	4	4
NF kappa B1 p50/RelA	-0.059	0.11	-9999	-0.66	2	2
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.65	16	16
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.031	0.15	-9999	-0.49	39	39
VAV3	-0.026	0.15	-9999	-0.46	44	44
MAP3K14	-0.039	0.15	-9999	-0.49	39	39
ROCK2	-0.028	0.18	-9999	-0.81	25	25
SPP1	-0.078	0.2	-9999	-0.42	104	104
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.045	0.13	-9999	-0.57	7	7
MMP2	-0.17	0.29	-9999	-0.66	101	101

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.038	0.037	-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	-0.057	0.11	-9999	-0.35	47	47
RXRs/LXRs/DNA/Oxysterols	-0.047	0.15	-9999	-0.46	57	57
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.021	0.083	-9999	-0.34	24	24
RXRs/NUR77	-0.26	0.25	-9999	-0.62	149	149
RXRs/PPAR	-0.054	0.064	-9999	-0.4	11	11
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0.009	-9999	-0.21	1	1
RARs/VDR/DNA/Vit D3	-0.013	0.079	-9999	-0.47	14	14
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	-0.013	0.078	-9999	-0.47	14	14
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.053	0.031	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.021	0.083	-9999	-0.34	24	24
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0.009	-9999	-0.21	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.082	-9999	-0.58	4	4
NR1H4	0.001	0.032	-9999	-0.31	5	5
RXRs/LXRs/DNA	-0.096	0.091	-9999	-0.57	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	-0.1	0.067	-9999	-0.52	4	4
NR4A1	-0.23	0.38	-9999	-0.81	147	147
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.047	0.048	-9999	-0.32	4	4
RXRG	-0.28	0.12	-9999	-0.31	437	437
RXR alpha/CCPG	0.021	0.009	-9999	-10000	0	0
RXRA	0.015	0.012	-9999	-10000	0	0
RXRB	0.015	0.014	-9999	-10000	0	0
THRB	-0.005	0.12	-9999	-0.81	11	11
PPARG	-0.002	0.1	-9999	-0.6	12	12
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.41	-9999	-1.3	57	57
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.046	0.15	-9999	-0.45	57	57
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.14	-9999	-0.81	14	14
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.44	172	172
SREBF1	-0.036	0.14	-9999	-0.62	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.082	-9999	-0.58	4	4
ABCA1	-0.036	0.14	-9999	-0.62	3	3
RARs/THRs	-0.023	0.1	-9999	-0.48	24	24
RXRs/FXR	-0.12	0.071	-9999	-0.55	4	4
BCL2	-0.047	0.22	-9999	-0.81	36	36

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.18	-9999	-0.46	65	65
IKBKB	-0.018	0.073	-9999	-0.29	7	7
AKT1	-0.042	0.1	-9999	-0.26	25	25
IKBKG	-0.017	0.077	-9999	-0.3	8	8
CALM1	-0.036	0.087	-9999	-0.35	3	3
PIK3CA	0.008	0.064	-9999	-0.81	3	3
MAP3K1	-0.076	0.18	-9999	-0.65	18	18
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.046	0.091	-9999	-0.37	3	3
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.081	0.13	-9999	-0.28	111	111
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	145	145
CD22	-0.15	0.23	-9999	-0.51	109	109
CAMK2G	-0.026	0.082	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	25	25
SHC/GRB2/SOS1	-0.098	0.15	-9999	-10000	0	0
GO:0007205	-0.046	0.092	-9999	-0.38	3	3
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.037	0.088	-9999	-0.35	3	3
NFATC1	-0.071	0.16	-9999	-0.55	22	22
B-cell antigen/BCR complex	-0.17	0.24	-9999	-0.52	145	145
PAG1/CSK	-0.002	0.029	-9999	-0.62	1	1
NFKBIB	0.003	0.028	-9999	-0.11	3	3
HRAS	-0.039	0.1	-9999	-0.34	4	4
NFKBIA	0.003	0.028	-9999	-0.11	3	3
NF-kappa-B/RelA/I kappa B beta	0.009	0.025	-9999	-0.19	1	1
RasGAP/Csk	-0.14	0.2	-9999	-0.49	100	100
mol:GDP	-0.042	0.084	-9999	-0.35	3	3
PTEN	0.012	0.037	-9999	-0.81	1	1
CD79B	-0.03	0.11	-9999	-0.31	67	67
NF-kappa-B/RelA/I kappa B alpha	0.009	0.025	-9999	-0.2	1	1
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.089	0.18	-9999	-0.43	77	77
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.052	0.089	-9999	-0.38	3	3
CSK	0.013	0.015	-9999	-0.31	1	1
FOS	-0.14	0.21	-9999	-0.47	127	127
CHUK	-0.017	0.077	-9999	-0.31	7	7
IBTK	0.013	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.068	0.1	-9999	-0.5	12	12
PTPN6	-0.14	0.21	-9999	-0.61	53	53
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.035	-9999	-0.13	19	19
VAV2	-0.14	0.19	-9999	-0.85	13	13
ubiquitin-dependent protein catabolic process	0.008	0.027	-9999	-0.11	3	3
BTK	-0.018	0.16	-9999	-1.2	8	8
CD19	-0.15	0.2	-9999	-0.46	102	102
MAP4K1	-0.021	0.13	-9999	-0.81	7	7
CD72	0.011	0.029	-9999	-0.31	4	4
PAG1	0.012	0.037	-9999	-0.81	1	1
MAPK14	-0.057	0.16	-9999	-0.53	18	18
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.036	0.09	-9999	-0.32	1	1
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.064	0.17	-9999	-0.43	76	76
RAF1	-0.029	0.096	-9999	-10000	0	0
RasGAP/p62DOK/SHIP	-0.14	0.2	-9999	-0.47	97	97
CD79A	-0.19	0.3	-9999	-0.52	190	190
re-entry into mitotic cell cycle	-0.08	0.13	-9999	-0.28	111	111
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.01	0.085	-9999	-10000	0	0
MAPK1	-0.01	0.085	-9999	-10000	0	0
CD72/SHP1	-0.1	0.21	-9999	-0.58	49	49
NFKB1	0.012	0.037	-9999	-0.81	1	1
MAPK8	-0.065	0.17	-9999	-0.54	26	26
actin cytoskeleton organization	-0.089	0.18	-9999	-0.68	13	13
NF-kappa-B/RelA	0.023	0.045	-9999	-0.2	1	1
Calcineurin	-0.036	0.06	-9999	-10000	0	0
PI3K	-0.13	0.16	-9999	-0.54	32	32
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.056	0.087	-9999	-0.34	3	3
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.11	0.24	-9999	-0.98	23	23
DAPP1	-0.14	0.26	-9999	-1.2	20	20
cytokine secretion	-0.066	0.15	-9999	-0.5	22	22
mol:DAG	-0.052	0.089	-9999	-0.38	3	3
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.019	0.091	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.17	0.24	-9999	-0.57	99	99
mol:PI-3-4-5-P3	-0.097	0.12	-9999	-0.36	32	32
ETS1	-0.017	0.077	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.17	-9999	-0.46	79	79
B-cell antigen/BCR complex/LYN	-0.12	0.2	-9999	-0.49	85	85
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.81	2	2
RAC1	-0.095	0.19	-9999	-0.75	13	13
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.55	85	85
CARD11	-0.075	0.14	-9999	-0.55	16	16
FCGR2B	-0.03	0.18	-9999	-0.73	29	29
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
IKK complex	0	0.036	-9999	-0.14	2	2
PTPRC	-0.034	0.18	-9999	-0.58	39	39
PDPK1	-0.044	0.1	-9999	-0.27	25	25
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.013	0	-9999	-10000	0	0
POU2F2	0.009	0.025	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.044	0.15	-9999	-0.54	39	39
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.051	-9999	-0.59	1	1
AP1	-0.25	0.36	-9999	-0.68	176	176
mol:PIP3	-0.041	0.12	-9999	-0.42	43	43
AKT1	-0.002	0.11	-9999	-0.58	5	5
PTK2B	0	0.085	-9999	-0.27	40	40
RHOA	0.031	0.046	-9999	-0.26	1	1
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.003	0.074	-9999	-10000	0	0
MAGI3	0.012	0.037	-9999	-0.81	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.014	0.13	-9999	-0.44	39	39
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.009	0.087	-9999	-0.42	5	5
NF kappa B1 p50/RelA	-0.044	0.12	-9999	-0.54	13	13
endothelial cell migration	-0.027	0.2	-9999	-0.64	41	41
ADCY4	-0.014	0.19	-9999	-0.61	40	40
ADCY5	-0.044	0.21	-9999	-0.64	43	43
ADCY6	-0.014	0.19	-9999	-0.61	40	40
ADCY7	-0.014	0.19	-9999	-0.61	40	40
ADCY1	-0.017	0.19	-9999	-0.62	40	40
ADCY2	-0.036	0.21	-9999	-0.66	40	40
ADCY3	-0.014	0.19	-9999	-0.61	40	40
ADCY8	-0.055	0.19	-9999	-0.63	43	43
ADCY9	-0.014	0.19	-9999	-0.61	40	40
GSK3B	0.009	0.081	-9999	-0.3	13	13
arachidonic acid secretion	-0.007	0.18	-9999	-0.5	53	53
GNG2	0.012	0.037	-9999	-0.81	1	1
TRIP6	0.026	0.008	-9999	-10000	0	0
GNAO1	-0.039	0.2	-9999	-0.59	54	54
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	-0.035	0.11	-9999	-0.97	6	6
JUN	-0.17	0.35	-9999	-0.81	112	112
LPA/LPA2/NHERF2	-0.001	0.007	-9999	-10000	0	0
TIAM1	-0.045	0.13	-9999	-1.2	6	6
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.003	0.075	-9999	-10000	0	0
PLCB3	0.03	0.009	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.81	127	127
positive regulation of mitosis	-0.007	0.18	-9999	-0.5	53	53
LPA/LPA1-2-3	-0.049	0.15	-9999	-0.54	39	39
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	0.004	0.11	-9999	-0.35	39	39
GNAZ	-0.02	0.17	-9999	-0.56	41	41
EGFR/PI3K-beta/Gab1	-0.043	0.13	-9999	-0.46	34	34
positive regulation of dendritic cell cytokine production	-0.049	0.15	-9999	-0.53	39	39
LPA/LPA2/MAGI-3	-0.002	0.027	-9999	-0.59	1	1
ARHGEF1	0	0.15	-9999	-0.49	39	39
GNAI2	-0.02	0.17	-9999	-0.56	41	41
GNAI3	-0.02	0.17	-9999	-0.56	41	41
GNAI1	-0.021	0.17	-9999	-0.56	42	42
LPA/LPA3	-0.01	0.044	-9999	-0.27	2	2
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.055	0.18	-9999	-0.65	41	41
HB-EGF/EGFR	-0.054	0.17	-9999	-0.53	50	50
HBEGF	-0.061	0.19	-9999	-0.61	45	45
mol:DAG	0.003	0.075	-9999	-10000	0	0
cAMP biosynthetic process	-0.026	0.2	-9999	-0.56	53	53
NFKB1	0.012	0.037	-9999	-0.81	1	1
SRC	0.013	0.015	-9999	-10000	0	0
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.01	0.079	-9999	-10000	0	0
GNAQ	0.019	0.029	-9999	-10000	0	0
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.003	0.065	-9999	-0.31	21	21
LPAR1	-0.05	0.23	-9999	-0.83	39	39
IL8	-0.13	0.2	-9999	-0.48	58	58
PTK2	-0.009	0.15	-9999	-0.5	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.014	0.13	-9999	-0.44	39	39
EGFR	0.005	0.083	-9999	-0.81	5	5
PLCG1	-0.016	0.085	-9999	-0.3	13	13
PLD2	-0.009	0.15	-9999	-0.5	39	39
G12/G13	-0.043	0.15	-9999	-0.53	39	39
PI3K-beta	-0.031	0.11	-9999	-0.7	5	5
cell migration	-0.016	0.059	-9999	-0.25	11	11
SLC9A3R2	0.013	0	-9999	-10000	0	0
PXN	0.004	0.11	-9999	-0.36	39	39
HRAS/GTP	-0.009	0.19	-9999	-0.52	53	53
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.083	0.24	-9999	-0.58	80	80
PRKCE	0.005	0.083	-9999	-0.82	5	5
PRKCD	0.011	0.072	-9999	-10000	0	0
Gi(beta/gamma)	-0.008	0.18	-9999	-0.58	40	40
mol:LPA	0.003	0.019	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.029	0.13	-9999	-0.45	39	39
MAPKKK cascade	-0.007	0.18	-9999	-0.5	53	53
contractile ring contraction involved in cytokinesis	0.031	0.045	-9999	-0.26	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.088	0.2	-9999	-0.43	118	118
GNA15	0.009	0.054	-9999	-0.35	2	2
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.009	0.089	-9999	-0.43	5	5
GNA11	0.01	0.069	-9999	-0.42	10	10
Rac1/GTP	-0.036	0.11	-9999	-1	6	6
MMP2	-0.028	0.2	-9999	-0.64	41	41

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.032	0.043	-9999	-0.92	1	1
VEGFR1 homodimer/NRP1	-0.002	0.042	-9999	-0.93	1	1
mol:DAG	-0.012	0.16	-9999	-0.48	51	51
VEGFR1 homodimer/NRP1/VEGFR 121	-0.005	0.067	-9999	-0.76	3	3
CaM/Ca2+	-0.004	0.15	-9999	-0.45	51	51
HIF1A	0.021	0.018	-9999	-0.38	1	1
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.009	0.16	-9999	-0.44	53	53
PLCG1	-0.012	0.16	-9999	-0.49	51	51
NOS3	0.017	0.15	-9999	-0.42	51	51
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.018	0.15	-9999	-0.41	51	51
FLT1	0.031	0.048	-9999	-1	1	1
PGF	-0.07	0.25	-9999	-0.81	50	50
VEGFR1 homodimer/NRP2/VEGFR121	-0.015	0.073	-9999	-0.76	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.81	3	3
eNOS/Hsp90	0.024	0.14	-9999	-0.39	51	51
endothelial cell proliferation	-0.024	0.19	-9999	-0.51	52	52
mol:Ca2+	-0.012	0.16	-9999	-0.48	51	51
MAPK3	-0.012	0.17	-9999	-0.43	68	68
MAPK1	-0.012	0.17	-9999	-0.43	68	68
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.07	0.25	-9999	-0.81	50	50
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.008	0.13	-9999	-0.81	13	13
VEGFA homodimer	0.008	0.064	-9999	-0.81	3	3
VEGFR1 homodimer/VEGFA homodimer	0.029	0.073	-9999	-0.82	3	3
platelet activating factor biosynthetic process	-0.004	0.17	-9999	-0.46	19	19
PI3K	-0.05	0.15	-9999	-0.46	53	53
PRKCA	-0.021	0.18	-9999	-0.46	68	68
PRKCB	-0.02	0.16	-9999	-0.46	55	55
VEGFR1 homodimer/PLGF homodimer	-0.025	0.18	-9999	-0.54	51	51
VEGFA	0.008	0.064	-9999	-0.81	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.012	0.16	-9999	-0.48	51	51
RASA1	0.041	0.04	-9999	-0.85	1	1
NRP2	-0.013	0.088	-9999	-0.31	40	40
VEGFR1 homodimer	0.03	0.047	-9999	-1	1	1
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.013	0.16	-9999	-0.42	51	51
PTPN11	0.012	0.037	-9999	-0.81	1	1
mol:PI-3-4-5-P3	-0.049	0.15	-9999	-0.46	53	53
mol:L-citrulline	0.018	0.15	-9999	-0.41	51	51
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.004	0.063	-9999	-0.72	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.005	0.066	-9999	-0.76	3	3
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.047	0.14	-9999	-0.44	53	53
PDPK1	0	0.16	-9999	-0.44	53	53
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.005	0.083	-9999	-0.89	3	3
mol:NADP	0.018	0.15	-9999	-0.41	51	51
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.004	0.061	-9999	-0.7	3	3
VEGFR1 homodimer/NRP2	0.018	0.065	-9999	-0.92	1	1

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.057	0.16	-9999	-0.55	43	43
MAP4K1	-0.021	0.13	-9999	-0.81	7	7
MAP3K8	0.002	0.098	-9999	-0.81	7	7
PRKCB	-0.022	0.12	-9999	-0.36	46	46
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.012	0.11	-9999	-0.55	6	6
JUN	-0.1	0.25	-9999	-0.51	123	123
MAP3K7	0.012	0.11	-9999	-0.55	6	6
GRAP2	-0.045	0.21	-9999	-0.75	38	38
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.018	0.11	-9999	-0.52	7	7
LAT	0.005	0.077	-9999	-0.65	6	6
LCP2	0.007	0.043	-9999	-0.31	9	9
MAPK8	-0.003	0.14	-9999	-0.75	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.003	0.12	-9999	-0.36	36	36
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.053	0.15	-9999	-0.52	43	43

×

Signaling events mediated by PTP1B

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
PDGFRB	0.012	0.037	-10000	0	-0.81	1	1
Jak2/Leptin Receptor	-0.025	0.097	0.2	18	-0.39	18	36
PTP1B/AKT1	-0.004	0.064	-10000	0	-0.3	4	4
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.013	0.07	-10000	0	-0.31	5	5
EGFR	0.003	0.084	-10000	0	-0.82	5	5
EGF/EGFR	-0.085	0.18	-10000	0	-0.5	77	77
CSF1	0	0.1	-10000	0	-0.81	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	-0.097	0.12	-10000	0	-0.33	52	52
Insulin Receptor/Insulin	-0.016	0.054	-10000	0	-0.44	4	4
HCK	-0.01	0.084	-10000	0	-0.31	36	36
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.004	0.067	-10000	0	-0.31	4	4
EGF	-0.11	0.29	-10000	0	-0.78	78	78
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.019	0.1	-10000	0	-0.36	8	8
TXN	0.011	0.015	-10000	0	-0.31	1	1
PTP1B/IRS1/GRB2	-0.055	0.17	-10000	0	-0.49	60	60
cell migration	0.013	0.07	0.31	5	-10000	0	5
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.044	0.19	-10000	0	-0.64	40	40
ITGA2B	-0.076	0.26	-10000	0	-0.82	53	53
CSF1R	0.008	0.049	-10000	0	-0.39	6	6
Prolactin Receptor/Prolactin	-0.039	0.15	-10000	0	-0.63	26	26
FGR	0.011	0.029	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.005	0.066	-10000	0	-0.31	4	4
Crk/p130 Cas	0	0.061	-10000	0	-0.34	2	2
DOK1	0.005	0.064	-10000	0	-0.3	3	3
JAK2	-0.013	0.092	-10000	0	-0.4	14	14
Jak2/Leptin Receptor/Leptin	-0.051	0.13	-10000	0	-0.56	25	25
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.013	0.071	-10000	0	-0.32	5	5
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.18	0.19	-10000	0	-0.34	279	279
SRC	0.011	0.03	-10000	0	-10000	0	0
ITGB3	-0.013	0.14	-10000	0	-0.82	15	15
CAT1/PTP1B	-0.09	0.15	-10000	0	-0.38	63	63
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.013	0.015	-10000	0	-0.31	1	1
PI3K	-0.018	0.061	-10000	0	-0.5	6	6
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.049	0.13	-10000	0	-0.6	24	24
negative regulation of transcription	-0.013	0.091	-10000	0	-0.39	14	14
FCGR2A	-0.007	0.084	-10000	0	-0.33	30	30
FER	0.007	0.065	-10000	0	-0.82	3	3
alphaIIb/beta3 Integrin	-0.083	0.23	-10000	0	-0.68	62	62
BLK	-0.24	0.37	-10000	0	-0.74	168	168
Insulin Receptor/Insulin/Shc	-0.003	0.042	-10000	0	-0.54	3	3
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	0.004	0.085	-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	-0.001	0.004	-10000	0	-10000	0	0
TRPV6	-0.12	0.19	-10000	0	-0.44	67	67
PRL	0.001	0.015	-10000	0	-0.3	1	1
SOCS3	-0.056	0.32	-10000	0	-1.5	23	23
SPRY2	0.009	0.055	-10000	0	-0.65	3	3
Insulin Receptor/Insulin/IRS1	-0.069	0.18	-10000	0	-0.55	62	62
CSF1/CSF1R	-0.009	0.094	-10000	0	-0.48	11	11
Ras protein signal transduction	0.021	0.023	-10000	0	-10000	0	0
IRS1	-0.085	0.27	-10000	0	-0.81	59	59
INS	-0.004	0.063	-10000	0	-0.82	3	3
LEP	-0.008	0.067	-10000	0	-0.31	23	23
STAT5B	-0.009	0.071	-10000	0	-0.27	10	10
STAT5A	-0.009	0.071	-10000	0	-0.27	10	10
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.069	-10000	0	-0.36	4	4
CSN2	-0.007	0.054	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
LAT	0.001	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	-0.42	27	27
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.13	0.16	-10000	0	-0.31	214	214

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.08	-9999	-0.71	6	6
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.57	16	16
PTK2	0.015	0.15	-9999	-0.53	17	17
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.025	0.1	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-10000	0	0
CDKN1B	-0.063	0.18	-9999	-0.61	45	45
VEGFA	0.008	0.064	-9999	-0.81	3	3
ILK	-0.063	0.18	-9999	-0.61	45	45
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.024	0.18	-9999	-0.56	45	45
PTK2B	0.018	0.11	-9999	-0.49	22	22
alphaV/beta3 Integrin/JAM-A	-0.059	0.16	-9999	-0.47	60	60
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.02	0.1	-9999	-0.57	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.26	-9999	-0.53	159	159
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.003	0.11	-9999	-0.54	3	3
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.1	-9999	-0.57	16	16
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.23	0.25	-9999	-0.55	169	169
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.81	3	3
alphaV/beta3 Integrin/Osteopontin	-0.069	0.16	-9999	-0.56	39	39
RPS6KB1	-0.2	0.24	-9999	-0.56	119	119
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.094	0.15	-9999	-0.74	16	16
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.094	0.15	-9999	-0.74	16	16
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.034	0.15	-9999	-0.61	28	28
cell adhesion	-0.029	0.099	-9999	-0.53	16	16
ANGPTL3	0.005	0.026	-9999	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.071	-9999	-0.62	6	6
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.008	0.064	-9999	-0.81	3	3
ITGB3	-0.012	0.14	-9999	-0.81	15	15
IGF1	-0.18	0.35	-9999	-0.79	119	119
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.1	-9999	-0.57	16	16
apoptosis	0.01	0.052	-9999	-0.81	2	2
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.018	0.1	-9999	-0.57	16	16
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.039	0.14	-9999	-0.6	24	24
CSF1	0	0.1	-9999	-0.81	8	8
PIK3C2A	-0.064	0.18	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.054	0.14	-9999	-0.77	3	3
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.024	0.11	-9999	-0.53	22	22
FAK1/Vinculin	0.023	0.12	-9999	-0.48	8	8
alphaV beta3/Integrin/ppsTEM5	-0.018	0.1	-9999	-0.57	16	16
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.067	0.24	-9999	-0.75	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	-0.037	0.11	-9999	-0.57	16	16
alphaV/beta3 Integrin/TGFBR2	-0.022	0.12	-9999	-0.59	18	18
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.01	0.075	-9999	-0.54	9	9
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.017	0.095	-9999	-0.53	16	16
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.14	-9999	-0.31	359	359
alphaV/beta3 Integrin/Pyk2	-0.022	0.11	-9999	-0.5	22	22
SDC1	0.01	0.032	-9999	-0.31	5	5
VAV3	0.026	0.097	-9999	-0.52	14	14
PTPN11	0.012	0.037	-9999	-0.81	1	1
IRS1	-0.085	0.27	-9999	-0.81	59	59
FAK1/Paxillin	0.023	0.12	-9999	-0.48	8	8
cell migration	0.033	0.12	-9999	-0.42	8	8
ITGAV	0.01	0.053	-9999	-0.81	2	2
PI3K	-0.055	0.15	-9999	-0.84	4	4
SPP1	-0.078	0.2	-9999	-0.42	104	104
KDR	0.007	0.074	-9999	-0.81	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.052	-9999	-0.81	2	2
COL4A3	-0.012	0.14	-9999	-0.81	15	15
angiogenesis	-0.083	0.18	-9999	-0.59	37	37
Rac1/GTP	-0.013	0.082	-9999	-0.47	14	14
EDIL3	-0.024	0.14	-9999	-0.43	42	42
cell proliferation	-0.021	0.11	-9999	-0.59	18	18

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.011	0.22	-10000	0	-0.97	21	21
NCK1/PAK1/Dok-R	-0.028	0.09	-10000	0	-0.43	21	21
NCK1/Dok-R	-0.068	0.25	-10000	0	-1.2	21	21
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
mol:beta2-estradiol	-0.003	0.047	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	0.26	4	-0.33	12	16
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.06	0.23	-10000	0	-1.1	21	21
FN1	-0.22	0.14	-10000	0	-0.31	359	359
PLD2	0	0.28	-10000	0	-1.3	21	21
PTPN11	0.012	0.037	-10000	0	-0.81	1	1
GRB14	-0.01	0.14	-10000	0	-0.81	14	14
ELK1	0.016	0.24	-10000	0	-1.1	21	21
GRB7	-0.04	0.12	-10000	0	-0.31	82	82
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.1	0.25	-10000	0	-1.2	21	21
CDKN1A	-0.009	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	-0.068	0.25	-10000	0	-1.2	21	21
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.027	0.17	-10000	0	-0.69	21	21
PLG	-0.009	0.28	-10000	0	-1.3	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.01	0.21	-10000	0	-0.93	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	-0.78	19	19
BMX	-0.014	0.29	-10000	0	-1.3	21	21
ANGPT1	-0.037	0.29	-10000	0	-1.5	18	18
tube development	-0.016	0.18	-10000	0	-0.73	21	21
ANGPT4	-0.061	0.23	-10000	0	-0.74	49	49
response to hypoxia	0	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.018	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)	-0.019	0.21	-10000	0	-0.84	21	21
mol:L-citrulline	0.027	0.17	-10000	0	-0.69	21	21
AGTR1	-0.32	0.4	-10000	0	-0.81	200	200
MAPK14	-0.011	0.27	-10000	0	-1.2	21	21
Tie2/SHP2	-0.027	0.16	-10000	0	-1.4	6	6
TEK	0.014	0.19	-10000	0	-1.5	6	6
RPS6KB1	0.011	0.21	-10000	0	-0.93	21	21
Angiotensin II/AT1	-0.25	0.32	-10000	0	-0.63	199	199
Tie2/Ang1/GRB2	-0.005	0.29	-10000	0	-1.3	21	21
MAPK3	0.011	0.25	-10000	0	-1.1	21	21
MAPK1	0.011	0.25	-10000	0	-1.1	21	21
Tie2/Ang1/GRB7	-0.028	0.29	-10000	0	-1.3	21	21
NFKB1	0.012	0.037	-10000	0	-0.81	1	1
MAPK8	-0.008	0.29	-10000	0	-1.3	21	21
PI3K	-0.004	0.26	-10000	0	-1.1	21	21
FES	-0.011	0.27	-10000	0	-1.2	21	21
Crk/Dok-R	-0.068	0.25	-10000	0	-1.2	21	21
Tie2/Ang1/ABIN2	-0.005	0.29	-10000	0	-1.3	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.016	0.2	-10000	0	-0.85	21	21
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.011	0.21	-10000	0	-0.93	21	21
Tie2/Ang2	-0.039	0.24	-10000	0	-1	21	21
Tie2/Ang1	-0.012	0.31	-10000	0	-1.4	21	21
FOXO1	0.022	0.2	-10000	0	-0.86	21	21
ELF1	0.015	0.078	-10000	0	-0.84	4	4
ELF2	-0.003	0.27	-10000	0	-1.2	21	21
mol:Choline	0.003	0.26	-10000	0	-1.2	21	21
cell migration	-0.023	0.055	-10000	0	-0.24	21	21
FYN	-0.022	0.21	-10000	0	-0.85	21	21
DOK2	-0.001	0.078	-10000	0	-0.36	19	19
negative regulation of cell cycle	-0.006	0.16	-10000	0	-0.58	21	21
ETS1	0.016	0.045	-10000	0	-10000	0	0
PXN	0.024	0.18	-10000	0	-0.75	21	21
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.024	0.19	-10000	0	-0.8	21	21
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.085	0.27	-10000	0	-0.77	64	64
MAPKKK cascade	0.003	0.26	-10000	0	-1.2	21	21
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.008	0.29	-10000	0	-1.3	21	21
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.03	0.15	-10000	0	-0.61	21	21
mol:Phosphatidic acid	0.003	0.26	-10000	0	-1.2	21	21
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.027	0.17	-10000	0	-0.69	21	21
Rac1/GTP	-0.049	0.18	-10000	0	-0.86	21	21
MMP2	-0.007	0.29	-10000	0	-1.3	21	21

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.003	0.04	-10000	0	-0.62	2	2
Necdin/E2F1	-0.067	0.11	-10000	0	-0.75	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.035	0.1	-10000	0	-0.48	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.28	-10000	0	-0.56	234	234
NT-4/5 (dimer)/p75(NTR)	-0.074	0.18	-10000	0	-0.66	37	37
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.003	0.12	-10000	0	-0.48	23	23
IKBKG	0.013	0	-10000	0	-10000	0	0
BDNF	-0.014	0.14	-10000	0	-0.61	22	22
MGDIs/NGR/p75(NTR)/LINGO1	-0.048	0.12	-10000	0	-0.56	18	18
FURIN	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.057	0.14	-10000	0	-0.54	32	32
LINGO1	-0.003	0.071	-10000	0	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.025	-10000	0	-10000	0	0
proBDNF (dimer)	-0.014	0.14	-10000	0	-0.61	22	22
NTRK1	-0.002	0.062	-10000	0	-0.31	19	19
RTN4R	0.013	0	-10000	0	-10000	0	0
neuron apoptosis	-0.01	0.13	-10000	0	-0.48	26	26
IRAK1	0.013	0	-10000	0	-10000	0	0
SHC1	-0.02	0.13	-10000	0	-0.56	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	-0.039	0.11	-10000	0	-0.51	20	20
MAGEH1	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.044	0.12	-10000	0	-0.51	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.49	25	25
proNGF (dimer)	0.006	0.069	-10000	0	-0.56	6	6
MAGED1	0.013	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.022	0.16	-10000	0	-0.66	26	26
ZNF274	0.013	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.036	0.1	-10000	0	-0.48	20	20
NGF	0.006	0.069	-10000	0	-0.56	6	6
cell cycle arrest	0.043	0.16	-10000	0	-0.46	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.085	-10000	0	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.064	0.16	-10000	0	-0.57	39	39
NCSTN	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.045	0.12	-10000	0	-0.56	21	21
PSENEN	0.013	0	-10000	0	-10000	0	0
mol:ceramide	-0.009	0.12	-10000	0	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.07	-10000	0	-0.43	2	2
p75(NTR)/beta APP	-0.049	0.13	-10000	0	-0.62	18	18
BEX1	-0.35	0.41	-10000	0	-0.81	219	219
mol:GDP	-0.03	0.13	-10000	0	-0.57	20	20
NGF (dimer)	-0.093	0.12	-10000	0	-0.5	30	30
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.042	0.11	-10000	0	-0.51	18	18
PIK3R1	0.013	0	-10000	0	-10000	0	0
RAC1/GTP	-0.038	0.1	-10000	0	-0.49	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	-0.045	0.12	-10000	0	-0.56	21	21
RHOB	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.061	0.092	-10000	0	-10000	0	0
NT3 (dimer)	-0.048	0.2	-10000	0	-0.6	49	49
TP53	-0.005	0.13	-10000	0	-0.44	32	32
PRDM4	-0.009	0.12	-10000	0	-0.51	20	20
BDNF (dimer)	-0.13	0.16	-10000	0	-0.53	41	41
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
SORT1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.035	0.1	-10000	0	-0.47	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.11	-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	0.023	0.12	-10000	0	-0.44	20	20
DIABLO	0.013	0	-10000	0	-10000	0	0
SMPD2	-0.009	0.12	-10000	0	-0.51	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	-0.044	0.12	-10000	0	-0.56	20	20
PSEN1	0.013	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-10000	0	-0.62	1	1
NT3 (dimer)/p75(NTR)	-0.092	0.2	-10000	0	-0.66	45	45
MAPK8	0.017	0.13	-10000	0	-0.45	20	20
MAPK9	0.024	0.12	-10000	0	-0.43	19	19
APAF1	0.012	0.037	-10000	0	-0.81	1	1
NTF3	-0.048	0.2	-10000	0	-0.6	49	49
NTF4	-0.022	0.16	-10000	0	-0.66	26	26
NDN	0.005	0.083	-10000	0	-0.81	5	5
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.032	0.094	-10000	0	-0.44	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.053	-10000	0	-0.65	3	3
RhoA-B-C/GTP	-0.045	0.12	-10000	0	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.048	0.12	-10000	0	-0.48	32	32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.052	0.13	-10000	0	-0.51	32	32
PRKACB	0.012	0.037	-10000	0	-0.81	1	1
proBDNF (dimer)/p75 ECD	-0.023	0.11	-10000	0	-0.62	15	15
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.65	37	37
BIRC2	0.013	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.066	0.17	0.24	188	-0.46	20	208
BAD	0.028	0.12	-10000	0	-0.43	20	20
RIPK2	0.013	0	-10000	0	-10000	0	0
NGFR	-0.06	0.18	-10000	0	-0.42	84	84
CYCS	0	0.11	-10000	0	-0.48	20	20
ADAM17	0.01	0.053	-10000	0	-0.81	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.041	0.11	-10000	0	-0.52	22	22
BCL2L11	0.028	0.12	-10000	0	-0.43	20	20
BDNF (dimer)/p75(NTR)	-0.069	0.16	-10000	0	-0.62	32	32
PI3K	-0.042	0.12	-10000	0	-0.52	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.039	0.11	-10000	0	-0.51	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)	-0.054	0.14	-10000	0	-0.65	20	20
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.039	0.11	-10000	0	-0.51	20	20
TRAF6	0.01	0.053	-10000	0	-0.81	2	2
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
PLG	-0.004	0.039	-10000	0	-0.31	8	8
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.017	0.14	-10000	0	-0.48	32	32
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	-0.085	0.15	-10000	0	-0.31	151	151
CASP9	0.013	0	-10000	0	-10000	0	0
IKK complex	-0.013	0.058	-10000	0	-0.53	3	3
NGF (dimer)/TRKA	-0.013	0.063	-10000	0	-0.63	3	3
MMP7	-0.17	0.22	-10000	0	-0.37	243	243
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.037	0.11	-10000	0	-0.48	22	22
MMP3	-0.039	0.11	-10000	0	-0.31	69	69
APAF-1/Caspase 9	-0.04	0.11	-10000	0	-0.6	7	7

×

Regulation of nuclear SMAD2/3 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
EP300	0.02	0.015	-10000	0	-10000	0	0
HSPA8	0.005	0.074	-10000	0	-0.81	4	4
SMAD3/SMAD4/ER alpha	-0.051	0.14	-10000	0	-0.58	24	24
AKT1	0.008	0.011	-10000	0	-10000	0	0
GSC	-0.2	0.54	-10000	0	-1.5	68	68
NKX2-5	0.002	0.028	-10000	0	-10000	0	0
muscle cell differentiation	0.025	0.05	0.44	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.006	0.08	-10000	0	-10000	0	0
SMAD4	-0.011	0.06	-10000	0	-0.26	1	1
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.076	-10000	0	-0.54	5	5
SMAD3/SMAD4/VDR	0.009	0.044	-10000	0	-10000	0	0
MYC	0.003	0.13	-10000	0	-0.82	12	12
CDKN2B	-0.075	0.14	-10000	0	-10000	0	0
AP1	-0.25	0.5	-10000	0	-0.95	151	151
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.055	-10000	0	-0.7	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.002	0.061	-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	-0.011	0.075	-10000	0	-0.31	23	23
SMAD3/SMAD4/GR	-0.017	0.046	-10000	0	-10000	0	0
GATA3	-0.031	0.18	-10000	0	-0.79	26	26
SKI/SIN3/HDAC complex/NCoR1	0.041	0.029	-10000	0	-10000	0	0
MEF2C/TIF2	-0.039	0.17	-10000	0	-0.6	20	20
endothelial cell migration	-0.007	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	0.064	-10000	0	-0.81	3	3
RUNX2	-0.072	0.15	-10000	0	-0.32	128	128
RUNX3	-0.012	0.13	-10000	0	-0.61	20	20
RUNX1	-0.13	0.16	-10000	0	-0.31	215	215
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	0.025	0.069	-10000	0	-10000	0	0
KAT2B	0.016	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.035	0.094	-10000	0	-0.44	3	3
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.012	0.004	-10000	0	-10000	0	0
SERPINE1	0.007	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.043	0.13	-10000	0	-0.59	22	22
SMAD3/SMAD4/ATF3	-0.16	0.26	-10000	0	-0.62	118	118
SAP30	0.01	0.037	-10000	0	-0.82	1	1
Cbp/p300/PIAS3	0.032	0.044	-10000	0	-10000	0	0
JUN	-0.24	0.5	-10000	0	-0.94	150	150
SMAD3/SMAD4/IRF7	-0.017	0.046	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.004	0.1	-10000	0	-1.2	1	1
mesenchymal cell differentiation	0.064	0.094	0.46	4	-10000	0	4
DLX1	-0.03	0.18	-10000	0	-0.81	26	26
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.22	0.39	-10000	0	-0.88	127	127
SMAD3/SMAD4/Max	-0.017	0.046	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.006	0.04	-10000	0	-0.54	2	2
ZBTB17	0.021	0.011	-10000	0	-10000	0	0
LAMC1	0.025	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.018	0.045	-10000	0	-10000	0	0
IRF7	0.014	0.015	-10000	0	-0.31	1	1
ESR1	-0.047	0.19	-10000	0	-0.52	55	55
HNF4A	-0.003	0.044	-10000	0	-0.31	10	10
MEF2C	0.005	0.097	-10000	0	-1	1	1
SMAD2-3/SMAD4	-0.032	0.055	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.024	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.016	0.025	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.017	0.01	-10000	0	-10000	0	0
SKIL	0.012	0.037	-10000	0	-0.81	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	0.053	-10000	0	-0.81	2	2
GCN5L2	0.005	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.01	0.048	-10000	0	-10000	0	0
MSG1/HSC70	-0.17	0.1	-10000	0	-0.68	9	9
SMAD2	-0.002	0.039	-10000	0	-10000	0	0
SMAD3	-0.005	0.048	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.074	-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	-0.067	0.24	-10000	0	-0.81	48	48
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	0.014	0.076	-10000	0	-10000	0	0
IFNB1	0.014	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.006	0.098	-10000	0	-1	1	1
CITED1	-0.26	0.14	-10000	0	-0.32	407	407
SMAD2-3/SMAD4/ARC105	-0.022	0.046	-10000	0	-10000	0	0
RBL1	-0.007	0.13	-10000	0	-0.81	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.005	0.08	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.083	0.11	-10000	0	-0.56	12	12
SMAD7	-0.1	0.28	-10000	0	-0.6	96	96
MYC/MIZ-1	0.014	0.11	-10000	0	-0.62	12	12
SMAD3/SMAD4	0.061	0.1	0.31	43	-0.35	1	44
IL10	-0.028	0.19	-10000	0	-0.62	39	39
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	-0.5	25	25
CDK4	0.018	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	125	125
SMAD3/SMAD4/SP1	-0.016	0.055	-10000	0	-10000	0	0
FOXG1	-0.001	0.06	-10000	0	-0.35	12	12
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	0.005	0.096	-10000	0	-0.99	1	1
CEBPB	0.009	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.048	0.14	-10000	0	-0.59	26	26
MYOD1	-0.001	0.028	-10000	0	-0.31	4	4
SMAD3/SMAD4/HNF4	-0.024	0.053	-10000	0	-0.4	1	1
SMAD3/SMAD4/GATA3	-0.052	0.14	-10000	0	-0.53	31	31
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.037	-10000	0	-0.81	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.076	0.11	-10000	0	-0.53	15	15
SMAD3/SMAD4/SP1-3	0.008	0.059	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.015	0.021	-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	-0.013	0.095	-10000	0	-0.52	2	2
ITGB5	0.036	0.06	-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	-0.59	209	209
AR	-0.34	0.41	-10000	0	-0.81	209	209
negative regulation of cell growth	-0.04	0.13	-10000	0	-0.44	8	8
SMAD3/SMAD4/MYOD	-0.023	0.05	-10000	0	-10000	0	0
E2F5	0.012	0.037	-10000	0	-0.81	1	1
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.01	0.067	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.066	-10000	0	-10000	0	0
TFDP1	0.012	0.037	-10000	0	-0.81	1	1
SMAD3/SMAD4/AP1	-0.26	0.51	-10000	0	-0.97	150	150
SMAD3/SMAD4/RUNX2	-0.064	0.094	-10000	0	-0.46	4	4
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.023	0.17	-10000	0	-0.81	22	22

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0.053	-9999	-0.81	2	2
Aurora C/Aurora B/INCENP	-0.04	0.076	-9999	-0.38	8	8
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.011	0.02	-9999	-10000	0	0
AURKB	-0.061	0.14	-9999	-0.31	113	113
AURKC	0	0.065	-9999	-0.31	21	21

×

Fc-epsilon receptor I signaling in mast cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.015	-9999	-0.31	1	1
LAT2	-0.018	0.1	-9999	-0.33	10	10
AP1	-0.2	0.28	-9999	-0.61	137	137
mol:PIP3	-0.016	0.15	-9999	-0.42	39	39
IKBKB	0.004	0.092	-9999	-0.28	15	15
AKT1	-0.015	0.14	-9999	-0.58	6	6
IKBKG	0.004	0.092	-9999	-0.26	20	20
MS4A2	-0.065	0.14	-9999	-0.31	114	114
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
MAP3K1	0.01	0.1	-9999	-0.46	7	7
mol:Ca2+	-0.008	0.12	-9999	-0.31	39	39
LYN	0.012	0.005	-9999	-10000	0	0
CBLB	-0.009	0.087	-9999	-0.35	4	4
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.081	0.18	-9999	-0.5	80	80
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	25	25
PLD2	-0.046	0.14	-9999	-0.44	39	39
PTPN13	-0.001	0.099	-9999	-0.55	6	6
PTPN11	0.011	0.039	-9999	-0.85	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.019	0.1	-9999	-0.34	6	6
SYK	0.012	0.005	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.062	0.13	-9999	-0.43	39	39
LAT	-0.014	0.098	-9999	-0.42	8	8
PAK2	0.002	0.11	-9999	-0.5	8	8
NFATC2	-0.15	0.28	-9999	-0.75	86	86
HRAS	-0.007	0.12	-9999	-0.5	11	11
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.03	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.096	0.16	-9999	-0.46	66	66
Antigen/IgE/Fc epsilon R1	-0.087	0.15	-9999	-0.42	66	66
mol:GDP	-0.016	0.13	-9999	-0.5	15	15
JUN	-0.17	0.35	-9999	-0.81	112	112
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.81	127	127
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.043	0.077	-9999	-0.32	8	8
CHUK	0.004	0.092	-9999	-0.28	14	14
KLRG1	-0.021	0.1	-9999	-0.41	14	14
VAV1	-0.022	0.11	-9999	-0.48	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.009	0.087	-9999	-0.35	4	4
negative regulation of mast cell degranulation	-0.019	0.1	-9999	-0.38	13	13
BTK	-0.021	0.12	-9999	-0.58	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.048	0.19	-9999	-0.52	46	46
GAB2/PI3K/SHP2	-0.063	0.12	-9999	-0.59	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.017	0.092	-9999	-0.29	34	34
RAF1	0.018	0.02	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.2	-9999	-0.58	56	56
FCER1G	-0.008	0.081	-9999	-0.32	32	32
FCER1A	-0.073	0.22	-9999	-0.54	75	75
Antigen/IgE/Fc epsilon R1/Fyn	-0.078	0.14	-9999	-0.47	40	40
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.81	1	1
MAPK8	0.005	0.11	-9999	-0.66	11	11
DUSP1	-0.12	0.3	-9999	-0.81	80	80
NF-kappa-B/RelA	-0.019	0.044	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.004	0.082	-9999	-0.33	3	3
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.042	0.1	-9999	-0.55	10	10
FER	-0.012	0.096	-9999	-0.43	7	7
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.073	0.17	-9999	-0.52	62	62
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.012	0.13	-9999	-0.53	12	12
cytokine secretion	-0.014	0.032	-9999	-0.22	1	1
SPHK1	-0.013	0.091	-9999	-0.37	5	5
PTK2	-0.004	0.084	-9999	-0.36	2	2
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.065	0.13	-9999	-0.42	47	47
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.01	0.14	-9999	-0.4	39	39
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	-0.046	0.092	-9999	-0.42	14	14
MAP2K4	0.021	0.007	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.2	-9999	-0.62	52	52
mol:Choline	-0.045	0.14	-9999	-0.44	39	39
SHC/Grb2/SOS1	-0.03	0.064	-9999	-0.39	1	1
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.004	0.08	-9999	-0.36	1	1
HCLS1	-0.012	0.092	-9999	-0.38	5	5
PRKCB	-0.009	0.12	-9999	-0.34	32	32
FCGR2B	-0.03	0.18	-9999	-0.73	29	29
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.019	0.1	-9999	-0.39	13	13
LCP2	0.007	0.043	-9999	-0.31	9	9
PLA2G4A	-0.039	0.15	-9999	-0.51	35	35
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.045	0.14	-9999	-0.44	39	39
IKK complex	0.019	0.075	-9999	-0.22	5	5
WIPF1	0.013	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.053	0.35	-9999	-0.91	13	13
PLK1	0.044	0.069	-9999	-10000	0	0
BIRC5	0.029	0.12	-9999	-1.5	1	1
HSPA1B	0.053	0.35	-9999	-0.9	14	14
MAP2K1	0.032	0.037	-9999	-10000	0	0
BRCA2	0.048	0.36	-9999	-0.97	17	17
FOXM1	0.043	0.39	-9999	-0.99	21	21
XRCC1	0.053	0.35	-9999	-0.9	14	14
FOXM1B/p19	-0.092	0.3	-9999	-0.86	30	30
Cyclin D1/CDK4	0.04	0.33	-9999	-0.85	14	14
CDC2	0.047	0.36	-9999	-0.88	21	21
TGFA	0.025	0.34	-9999	-0.84	16	16
SKP2	0.046	0.36	-9999	-0.97	17	17
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.053	0.35	-9999	-0.91	13	13
RB1	-0.052	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.039	0.36	-9999	-0.96	21	21
AURKB	-0.005	0.12	-9999	-10000	0	0
CENPF	0.048	0.36	-9999	-0.94	14	14
CDK4	0.019	0.015	-9999	-10000	0	0
MYC	0.047	0.35	-9999	-0.92	21	21
CHEK2	0.032	0.037	-9999	-10000	0	0
ONECUT1	0.037	0.34	-9999	-0.89	15	15
CDKN2A	-0.12	0.16	-9999	-0.31	204	204
LAMA4	0.053	0.35	-9999	-0.9	14	14
FOXM1B/HNF6	0.031	0.37	-9999	-0.99	17	17
FOS	-0.18	0.65	-9999	-1.2	128	128
SP1	0.014	0.005	-9999	-10000	0	0
CDC25B	0.053	0.35	-9999	-0.91	14	14
response to radiation	0.016	0.034	-9999	-10000	0	0
CENPB	0.053	0.35	-9999	-0.9	14	14
CENPA	0.039	0.37	-9999	-0.96	20	20
NEK2	0.044	0.36	-9999	-0.92	17	17
HIST1H2BA	0.045	0.35	-9999	-0.91	14	14
CCNA2	0.01	0.049	-9999	-0.32	10	10
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.042	0.37	-9999	-1	15	15
CCNB2	0.05	0.35	-9999	-0.93	15	15
CCNB1	0.049	0.36	-9999	-0.94	15	15
ETV5	0.053	0.35	-9999	-0.91	14	14
ESR1	0.006	0.43	-9999	-1.1	35	35
CCND1	0.043	0.34	-9999	-0.87	14	14
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.051	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.12	0.22	-9999	-0.87	22	22
GAS1	-0.12	0.6	-9999	-1.2	104	104
MMP2	0.044	0.38	-9999	-1.1	17	17
RB1/FOXM1C	0.051	0.34	-9999	-0.9	15	15
CREBBP	0.013	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.017	0.085	-9999	-0.47	16	16
RGS9BP	-0.037	0.2	-9999	-0.81	30	30
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.066	0.24	-9999	-0.81	47	47
mol:Na +	-0.021	0.056	-9999	-10000	0	0
mol:ADP	-0.044	0.19	-9999	-0.63	47	47
GNAT2	0.009	0.021	-9999	-0.31	2	2
RGS9-1/Gbeta5/R9AP	-0.088	0.2	-9999	-0.55	78	78
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	-0.29	2	2
Cone PDE6	-0.076	0.18	-9999	-0.48	78	78
Cone Metarhodopsin II	-0.049	0.15	-9999	-0.51	47	47
Na + (4 Units)	-0.025	0.057	-9999	-10000	0	0
GNAT2/GDP	-0.076	0.18	-9999	-0.48	78	78
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.015	-9999	-10000	0	0
Cone Transducin	-0.018	0.089	-9999	-0.5	16	16
SLC24A2	-0.009	0.064	-9999	-0.31	21	21
GNB3/GNGT2	-0.022	0.11	-9999	-0.62	16	16
GNB3	-0.012	0.14	-9999	-0.78	16	16
GNAT2/GTP	-0.001	0.013	-9999	-0.21	2	2
CNGA3	-0.027	0.11	-9999	-0.31	61	61
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.056	-9999	-10000	0	0
mol:Pi	-0.087	0.2	-9999	-0.55	78	78
Cone CNG Channel	-0.016	0.042	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.009	0.064	-9999	-0.31	21	21
RGS9	-0.072	0.25	-9999	-0.79	53	53
PDE6C	0.003	0.015	-9999	-0.31	1	1
GNGT2	0.009	0.047	-9999	-0.41	5	5
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.004	0.006	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.014	0.094	-10000	0	-0.45	1	1
epithelial cell differentiation	-0.047	0.1	-10000	0	-0.47	12	12
ITCH	0.024	0.02	-10000	0	-10000	0	0
WWP1	-0.001	0.08	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.005	0.083	-10000	0	-0.81	5	5
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	-0.017	0.14	-10000	0	-0.56	24	24
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.057	0.13	-10000	0	-0.56	11	11
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.043	0.17	-10000	0	-0.52	47	47
ADAM17	0.021	0.057	-10000	0	-0.81	2	2
ErbB4/ErbB4	-0.012	0.1	-10000	0	-0.51	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.045	0.17	-10000	0	-0.55	37	37
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.066	0.14	-10000	0	-0.49	46	46
GRIN2B	-0.028	0.15	-10000	0	-0.46	46	46
ErbB4/ErbB2/betacellulin	-0.04	0.12	-10000	0	-0.6	17	17
STAT1	0.006	0.05	-10000	0	-0.31	12	12
HBEGF	-0.004	0.072	-10000	0	-0.31	26	26
PRLR	-0.044	0.19	-10000	0	-0.59	47	47
E4ICDs/ETO2	-0.007	0.091	-10000	0	-0.56	2	2
axon guidance	-0.001	0.086	-10000	0	-0.43	3	3
NEDD4	0.021	0.056	-10000	0	-0.8	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.043	0.15	-10000	0	-0.63	26	26
CBFA2T3	0.01	0.042	-10000	0	-0.48	3	3
ErbB4/ErbB2/HBEGF	-0.03	0.061	-10000	0	-0.57	2	2
MAPK3	-0.005	0.14	-10000	0	-0.53	10	10
STAT1 (dimer)	-0.009	0.091	-10000	0	-0.45	1	1
MAPK1	-0.005	0.14	-10000	0	-0.53	10	10
JAK2	0.01	0.053	-10000	0	-0.81	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.033	0.16	-10000	0	-0.49	46	46
NRG1	-0.032	0.2	-10000	0	-0.64	46	46
NRG3	-0.047	0.22	-10000	0	-0.81	36	36
NRG2	-0.079	0.26	-10000	0	-0.79	57	57
NRG4	0.008	0.035	-10000	0	-0.31	6	6
heart development	-0.001	0.086	-10000	0	-0.43	3	3
neural crest cell migration	-0.032	0.16	-10000	0	-0.48	46	46
ERBB2	0.028	0.042	-10000	0	-0.61	2	2
WWOX/E4ICDs	-0.006	0.093	-10000	0	-0.94	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.038	0.086	-10000	0	-0.61	5	5
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	55	55
ErbB4/ErbB2/epiregulin	-0.079	0.087	-10000	0	-0.54	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.023	0.14	-10000	0	-0.63	18	18
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.061	0.12	-10000	0	-0.48	28	28
MDM2	-0.001	0.088	-10000	0	-0.45	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.061	0.14	-10000	0	-0.5	46	46
STAT5A	0.007	0.081	-10000	0	-0.44	2	2
ErbB4/EGFR/neuregulin 1 beta	-0.071	0.16	-10000	0	-0.51	50	50
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.033	0.064	-10000	0	-0.42	1	1
STAT5A (dimer)	-0.05	0.11	-10000	0	-0.51	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.08	-10000	0	-0.51	1	1
LRIG1	0	0.1	-10000	0	-0.81	8	8
EREG	-0.14	0.16	-10000	0	-0.31	230	230
BTC	-0.015	0.15	-10000	0	-0.81	17	17
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.087	-10000	0	-0.44	3	3
ERBB4	-0.012	0.1	-10000	0	-0.52	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.011	0.02	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.026	0.057	-10000	0	-0.5	2	2
glial cell differentiation	0.033	0.063	0.42	1	-10000	0	1
WWOX	0.012	0.037	-10000	0	-0.81	1	1
cell proliferation	-0.025	0.17	-10000	0	-0.45	56	56

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.027	0.064	-9999	-0.32	7	7
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	0.24	-9999	-0.66	75	75
IL1A	-0.053	0.22	-9999	-0.78	41	41
IL1B	-0.026	0.17	-9999	-0.63	36	36
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-0.42	2	2
IL1R2	-0.082	0.24	-9999	-0.58	79	79
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.006	0.067	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.005	0.083	-9999	-0.81	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.066	0.027	-9999	-10000	0	0
JUN	-0.073	0.22	-9999	-0.43	124	124
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.061	0.13	-9999	-0.47	37	37
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.072	0.14	-9999	-0.5	38	38
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.065	0.13	-9999	-0.47	38	38
IL1 beta fragment/IL1R1/IL1RAP	-0.071	0.14	-9999	-0.52	35	35
NFKB1	0.012	0.037	-9999	-0.81	1	1
MAPK8	0.019	0.11	-9999	-0.52	19	19
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.043	0.11	-9999	-0.62	11	11
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.81	2	2
PI3K	-0.004	0.048	-9999	-0.62	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.001	0.082	-9999	-0.34	7	7
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.071	0.14	-9999	-0.52	35	35
IL1 beta/IL1R2	-0.098	0.22	-9999	-0.59	72	72
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.028	-9999	-0.44	2	2
NF kappa B1 p50/RelA	-0.053	0.11	-9999	-0.55	7	7
IRAK3	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.063	0.13	-9999	-0.48	40	40
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.014	0.1	-9999	-0.43	4	4
IL1 alpha/IL1R1/IL1RAP	-0.082	0.15	-9999	-0.55	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	-0.46	2	2
IL1RAP	-0.069	0.14	-9999	-0.31	126	126
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.049	0.11	-9999	-0.49	11	11
CASP1	0.007	0.062	-9999	-0.45	7	7
IL1RN/IL1R2	-0.11	0.21	-9999	-0.61	62	62
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.064	0.13	-9999	-0.49	35	35
TMEM189-UBE2V1	0.004	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.08	-9999	-0.33	4	4
PIK3CA	0.008	0.064	-9999	-0.81	3	3
IL1RN	-0.052	0.16	-9999	-0.38	83	83
TRAF6/TAK1/TAB1/TAB2	-0.002	0.029	-9999	-0.46	2	2
MAP2K6	0.021	0.075	-9999	-0.43	13	13

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.24	0.38	-10000	0	-0.81	151	151
HRAS	0.012	0.021	-10000	0	-0.31	2	2
EGFR	0.005	0.083	-10000	0	-0.81	5	5
AKT	0.019	0.025	0.2	1	-10000	0	1
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	-0.1	0.16	-10000	0	-0.31	179	179
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.014	0.14	-10000	0	-0.73	18	18
PIK3R3	0.012	0.037	-10000	0	-0.81	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.058	0.098	-10000	0	-0.26	42	42
ERBB2	0.013	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.024	0.024	0.18	2	-0.17	1	3
PI3K	-0.039	0.095	0.22	1	-0.22	50	51
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.025	0.027	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.037	-10000	0	-0.81	1	1

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.001	0.079	-9999	-10000	0	0
STMN1	-0.022	0.094	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.024	0.11	-9999	-0.32	34	34
Chromosomal passenger complex/Cul3 protein complex	0.007	0.069	-9999	-0.28	14	14
BIRC5	-0.011	0.091	-9999	-0.33	35	35
DES	-0.38	0.3	-9999	-0.61	300	300
Aurora C/Aurora B/INCENP	-0.016	0.087	-9999	-0.39	7	7
Aurora B/TACC1	-0.022	0.08	-9999	-0.7	1	1
Aurora B/PP2A	-0.027	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.005	0.026	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.046	0.14	-9999	-0.39	56	56
Cul3 protein complex	-0.018	0.086	-9999	-0.54	12	12
KIF2C	0	0.042	-9999	-0.18	2	2
PEBP1	0.011	0.005	-9999	-10000	0	0
KIF20A	-0.035	0.12	-9999	-0.31	74	74
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.027	0.091	-9999	-10000	0	0
SEPT1	0.007	0.043	-9999	-0.31	9	9
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.007	0.044	-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	-0.008	0.055	-9999	-10000	0	0
AURKB	-0.052	0.14	-9999	-0.31	113	113
AURKC	0	0.065	-9999	-0.31	21	21
CDCA8	0.01	0.03	-9999	-0.32	4	4
cytokinesis	-0.064	0.081	-9999	-0.39	11	11
Aurora B/Septin1	-0.025	0.1	-9999	-0.42	10	10
AURKA	0.013	0.002	-9999	-10000	0	0
INCENP	0.009	0.054	-9999	-0.83	2	2
KLHL13	-0.017	0.14	-9999	-0.53	27	27
BUB1	-0.1	0.16	-9999	-0.31	171	171
hSgo1/Aurora B/Survivin	-0.024	0.11	-9999	-0.44	17	17
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.029	0.071	-9999	-0.36	4	4
SGOL1	0.001	0.062	-9999	-0.31	19	19
CENPA	-0.008	0.07	-9999	-0.22	20	20
NCAPG	-0.019	0.097	-9999	-0.31	49	49
Aurora B/HC8 Proteasome	-0.027	0.091	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.027	0.091	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.036	0.12	-9999	-0.31	75	75
NPM1	-0.012	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	-0.027	0.09	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.034	0.079	-9999	-0.35	18	18
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.048	-9999	-10000	0	0
MYLK	-0.008	0.06	-9999	-0.55	1	1
KIF23	-0.003	0.072	-9999	-0.32	25	25
VIM	-0.022	0.092	-9999	-10000	0	0
RACGAP1	0.013	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.048	-9999	-10000	0	0
Chromosomal passenger complex	-0.012	0.081	-9999	-0.25	25	25
Chromosomal passenger complex/EVI5	0.011	0.12	-9999	-0.47	7	7
TACC1	0.012	0.037	-9999	-0.81	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 S69. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.003	0.077	-10000	0	-0.36	8	8
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	0.037	-10000	0	-0.81	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.041	0.077	0.23	16	-0.27	12	28
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	0.22	-10000	0	-0.62	69	69
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	0.024	-10000	0	-0.54	1	1
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.03	0.11	-10000	0	-0.31	64	64
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	0.082	0.26	2	-0.3	12	14
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.027	0	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.33	312	312
LNPEP	-0.013	0.15	-10000	0	-0.81	16	16
YWHAE	0.013	0	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.04	0.12	-9999	-0.42	46	46
Syndecan-3/Neurocan	-0.033	0.12	-9999	-0.46	34	34
POMC	-0.16	0.34	-9999	-0.8	106	106
EGFR	0.005	0.083	-9999	-0.81	5	5
Syndecan-3/EGFR	-0.005	0.046	-9999	-0.46	5	5
AGRP	-0.006	0.064	-9999	-0.31	21	21
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	-0.048	0.21	-9999	-0.75	39	39
long-term memory	0	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.039	0.081	-9999	-0.46	11	11
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	0.045	-9999	-0.31	10	10
SRC	0.013	0.015	-9999	-10000	0	0
PTN	-0.064	0.24	-9999	-0.81	46	46
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	-0.066	0.15	-9999	-0.6	3	3
Syndecan-3/AgRP	-0.006	0.025	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.008	0.029	-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	-0.039	0.08	-9999	-0.45	11	11
IL8	-0.082	0.18	-9999	-0.35	128	128
Syndecan-3/Fyn/Cortactin	0	0.005	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.14	0.26	-9999	-0.63	103	103
Gamma Secretase	0	0	-9999	-10000	0	0

×

Effects of Botulinum toxin

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	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	-0.013	0.065	-9999	-0.2	39	39
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	0.04	-9999	-0.15	29	29
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.044	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.013	0.065	-9999	-0.2	39	39
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.015	0.093	-9999	-0.32	39	39
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.1	0.16	-9999	-0.6	30	30
SNAP25	-0.031	0.095	-9999	-0.38	29	29
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.16	0.22	-9999	-0.38	219	219
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.044	-9999	-10000	0	0

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.062	0.16	-10000	0	-0.47	65	65
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.055	-10000	0	-0.21	34	34
GNB1/GNG2	-0.001	0.025	-10000	0	-0.55	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	-0.067	0.17	-10000	0	-0.51	64	64
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	64	-10000	0	64
GNAL	-0.094	0.28	-10000	0	-0.81	64	64
GNG2	0.012	0.037	-10000	0	-0.81	1	1
CRH	-0.014	0.081	-10000	0	-0.31	34	34
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.069	-10000	0	-0.46	11	11
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.063	0.08	-10000	0	-0.34	22	22
NT3 (dimer)/TRKC	-0.087	0.19	-10000	0	-0.67	39	39
NT3 (dimer)/TRKB	-0.083	0.18	-10000	0	-0.57	50	50
SHC/Grb2/SOS1/GAB1/PI3K	0.037	0.028	-10000	0	-0.33	3	3
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.014	0.14	-10000	0	-0.61	22	22
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.002	0.062	-10000	0	-0.31	19	19
NTRK2	0.005	0.083	-10000	0	-0.81	5	5
NTRK3	-0.054	0.16	-10000	0	-0.38	84	84
NT-4/5 (dimer)/TRKB	-0.068	0.16	-10000	0	-0.57	42	42
neuron apoptosis	0.04	0.091	0.42	15	-10000	0	15
SHC 2-3/Grb2	-0.042	0.099	-10000	0	-0.46	15	15
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.029	0.092	-10000	0	-0.63	6	6
SHC3	-0.047	0.1	-10000	0	-0.55	12	12
STAT3 (dimer)	0.018	0.025	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.084	0.17	-10000	0	-0.56	47	47
RIN/GDP	-0.008	0.061	-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	-0.032	0.091	-10000	0	-0.41	23	23
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.026	0.045	-10000	0	-10000	0	0
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.012	0.037	-10000	0	-0.81	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.022	0.16	-10000	0	-0.66	26	26
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.019	0.079	-10000	0	-0.5	10	10
TRKA/NEDD4-2	-0.008	0.038	-10000	0	-10000	0	0
ELMO1	-0.31	0.4	-10000	0	-0.81	192	192
RhoG/GTP/ELMO1/DOCK1	-0.22	0.27	-10000	0	-0.55	193	193
NGF	0.006	0.069	-10000	0	-0.56	6	6
HRAS	0.012	0.021	-10000	0	-0.31	2	2
DOCK1	0.007	0.074	-10000	0	-0.81	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	-0.014	0.15	-10000	0	-0.78	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	-0.2	0.23	-10000	0	-0.46	209	209
mol:GDP	-0.014	0.088	-10000	0	-0.39	4	4
NGF (dimer)	0.006	0.069	-10000	0	-0.56	6	6
RhoG/GDP	-0.25	0.31	-10000	0	-0.63	192	192
RIT1/GDP	-0.003	0.062	-10000	0	-0.28	2	2
TIAM1	-0.17	0.16	-10000	0	-0.81	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.022	0.11	-10000	0	-0.57	17	17
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.024	-10000	0	-0.54	1	1
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.048	0.2	-10000	0	-0.6	49	49
RAP1/GDP	-0.017	0.041	-10000	0	-0.25	1	1
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.014	0.14	-10000	0	-0.61	22	22
ubiquitin-dependent protein catabolic process	-0.01	0.052	-10000	0	-0.54	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	0.016	-10000	0	-0.32	1	1
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.065	0.14	-10000	0	-0.5	25	25
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.036	-10000	0	-10000	0	0
STAT3	0.018	0.025	-10000	0	-10000	0	0
axon guidance	-0.063	0.14	-10000	0	-0.43	54	54
MAPK3	0.014	0.078	-10000	0	-0.49	8	8
MAPK1	0.014	0.078	-10000	0	-0.49	8	8
CDC42/GDP	-0.003	0.062	-10000	0	-0.28	2	2
NTF3	-0.048	0.2	-10000	0	-0.6	49	49
NTF4	-0.022	0.16	-10000	0	-0.66	26	26
NGF (dimer)/TRKA/FAIM	-0.01	0.052	-10000	0	-0.54	3	3
PI3K	-0.004	0.048	-10000	0	-0.62	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	28	28
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.05	0.17	-10000	0	-0.58	39	39
RGS19	0.013	0.015	-10000	0	-0.31	1	1
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.046	-10000	0	-0.42	1	1
Rac1/GDP	-0.003	0.062	-10000	0	-0.28	2	2
NGF (dimer)/TRKA/GRIT	-0.011	0.054	-10000	0	-0.55	3	3
neuron projection morphogenesis	0	0.093	-10000	0	-0.52	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.01	0.052	-10000	0	-0.54	3	3
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.06	0.18	-10000	0	-0.42	84	84
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.076	-10000	0	-0.35	18	18
RAS family/GTP/PI3K	0.03	0.031	-10000	0	-0.36	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	0.056	-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	0.098	-10000	0	-0.52	17	17
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.008	0.042	-10000	0	-0.46	3	3
MATK	-0.003	0.096	-10000	0	-0.46	17	17
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.014	0.041	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.035	0.097	-10000	0	-0.44	23	23
Rac1/GTP	-0.19	0.14	-10000	0	-0.35	196	196
FRS2 family/SHP2/CRK family	-0.001	0.021	-10000	0	-0.46	1	1

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.015	0.057	-9999	-0.55	5	5
ADCY5	-0.057	0.19	-9999	-0.55	66	66
ADCY6	0.015	0.057	-9999	-0.55	5	5
ADCY7	0.015	0.057	-9999	-0.55	5	5
ADCY1	0.008	0.09	-9999	-0.62	9	9
ADCY2	-0.039	0.17	-9999	-0.56	46	46
ADCY3	0.015	0.057	-9999	-0.55	5	5
ADCY8	-0.12	0.1	-9999	-0.7	5	5
PRKCE	0.006	0.065	-9999	-0.63	5	5
ADCY9	0.015	0.057	-9999	-0.55	5	5
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.055	0.1	-9999	-0.37	31	31

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.019	0.12	-10000	0	-0.78	12	12
HDAC1	0.002	0.008	-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	0.002	0.098	-10000	0	-0.81	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.008	0.064	-10000	0	-0.81	3	3
AP1	-0.14	0.26	-10000	0	-0.52	139	139
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.007	0.13	-10000	0	-0.81	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.052	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.018	0.11	-10000	0	-0.73	12	12
WIF1	-0.033	0.1	-10000	0	-0.31	60	60
NOTCH1	-0.019	0.12	-10000	0	-0.76	12	12
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.01	0.083	-10000	0	-0.31	35	35
DKK1	-0.041	0.13	-10000	0	-0.32	80	80
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	0.037	-10000	0	-0.22	1	1
CtBP/CBP/TCF1/TLE1/AES	0.024	0.036	-10000	0	-0.34	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.2	0.36	-10000	0	-0.81	127	127
JUN	-0.17	0.35	-10000	0	-0.81	112	112
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	-0.034	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	-0.011	0.24	-10000	0	-1.5	12	12
NKD1	-0.013	0.14	-10000	0	-0.7	18	18
FZD1	0.013	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.024	0.12	-10000	0	-0.62	19	19
apoptosis	-0.14	0.26	-10000	0	-0.52	139	139
Delta 1/NOTCHprecursor	-0.019	0.12	-10000	0	-0.75	12	12
DLL1	0.011	0.04	-10000	0	-0.56	2	2
PPARD	0.024	0.016	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.06	-10000	0	-1.1	1	1
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	-0.038	0.08	-10000	0	-0.39	9	9
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.015	0.007	-10000	0	-10000	0	0
CCND1	0.018	0.044	-10000	0	-10000	0	0
WNT1	0.008	0.033	-10000	0	-0.31	5	5
Axin1/APC/beta catenin	0.042	0.052	-10000	0	-0.67	1	1
DKK2	-0.024	0.16	-10000	0	-0.65	28	28
NOTCH1 precursor/DVL1	-0.012	0.1	-10000	0	-0.64	12	12
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	19	19
PPP2R5D	0.011	0.063	0.37	14	-10000	0	14
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.017	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

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0	-10000	0	-10000	0	0
MAP4K4	-0.002	0.14	-10000	0	-0.7	11	11
BAG4	0.012	0.037	-10000	0	-0.81	1	1
PKC zeta/ceramide	-0.018	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.65	37	37
BAX	-0.006	0.02	-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	-0.018	0.041	-10000	0	-10000	0	0
SMPD1	-0.005	0.094	-10000	0	-0.26	57	57
RB1	-0.019	0.046	-10000	0	-0.49	1	1
FADD/Caspase 8	0.01	0.13	-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	-0.51	2	2
EGF	-0.11	0.29	-10000	0	-0.78	78	78
mol:ceramide	-0.029	0.043	-10000	0	-0.13	68	68
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	0.029	-10000	0	-0.62	1	1
ASAH1	0.012	0.037	-10000	0	-0.81	1	1
negative regulation of cell cycle	-0.019	0.045	-10000	0	-0.49	1	1
cell proliferation	-0.097	0.16	-10000	0	-0.39	114	114
BID	-0.015	0.091	-10000	0	-0.4	11	11
MAP3K1	-0.018	0.041	-10000	0	-10000	0	0
EIF2A	-0.001	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	-0.47	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.002	0.047	-10000	0	-0.47	2	2
Cathepsin D/ceramide	-0.018	0.041	-10000	0	-10000	0	0
FADD	-0.002	0.14	-10000	0	-0.7	11	11
KSR1	-0.019	0.052	-10000	0	-0.54	2	2
MAPK8	-0.01	0.06	-10000	0	-0.32	11	11
PRKRA	-0.018	0.041	-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	-0.79	119	119
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.043	-10000	0	-0.13	68	68
CTSD	0.013	0.015	-10000	0	-0.31	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.028	-10000	0	-0.62	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.084	0.19	-10000	0	-0.42	114	114
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	0.029	-10000	0	-0.62	1	1
RelA/NF kappa B1	-0.001	0.028	-10000	0	-0.62	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	-0.011	0.15	-10000	0	-0.74	11	11
TNFR1A/BAG4/TNF-alpha	-0.065	0.17	-10000	0	-0.54	58	58
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.003	0.048	-10000	0	-0.48	2	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	0.003	0.052	0.18	27	-10000	0	27
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.012	0.037	-10000	0	-0.81	1	1
TNFR1A/BAG4	-0.001	0.028	-10000	0	-0.62	1	1
EIF2AK2	-0.009	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.064	0.17	-10000	0	-0.54	57	57
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.079	-10000	0	-0.33	11	11
MAP2K2	-0.003	0.048	-10000	0	-0.48	2	2
SMPD3	-0.011	0.12	-10000	0	-0.3	62	62
TNF	-0.087	0.26	-10000	0	-0.76	64	64
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.024	0.11	0.28	72	-0.13	2	74
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	27	-10000	0	27
BCL2	-0.047	0.22	-10000	0	-0.81	36	36

×

IL2 signaling events mediated by STAT5

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
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.014	0.12	-9999	-0.44	32	32
CCNA2	0.007	0.046	-9999	-0.31	10	10
PIK3CA	0.009	0.064	-9999	-0.81	3	3
JAK3	-0.068	0.14	-9999	-0.31	125	125
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	-0.57	19	19
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.044	0.25	-9999	-0.97	32	32
IL2RB	-0.014	0.13	-9999	-0.5	27	27
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.048	0.19	-9999	-0.52	57	57
G1/S transition of mitotic cell cycle	0.039	0.054	-9999	-0.59	3	3
PTPN11	0.013	0.037	-9999	-0.81	1	1
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.01	0.11	-9999	-0.42	27	27
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.005	0.006	-9999	-10000	0	0
CDK6	0.008	0.064	-9999	-0.81	3	3
CCND3	0.027	0.13	-9999	-0.62	8	8

×

Insulin Pathway

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
CBL/APS/CAP	-0.057	0.15	-9999	-0.44	64	64
TC10/GTP	-0.004	0.037	-9999	-0.42	4	4
Insulin Receptor/Insulin/IRS1/Shp2	-0.064	0.17	-9999	-0.51	62	62
HRAS	0.012	0.021	-9999	-0.31	2	2
APS homodimer	0.013	0.015	-9999	-0.31	1	1
GRB14	-0.01	0.14	-9999	-0.81	14	14
FOXO3	-0.023	0.1	-9999	-0.69	10	10
AKT1	-0.015	0.16	-9999	-0.88	2	2
INSR	0.015	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin	0.035	0.036	-9999	-0.42	3	3
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.007	0.074	-9999	-0.81	4	4
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.035	0.035	-9999	-0.41	3	3
CAV1	-0.047	0.18	-9999	-0.47	75	75
CBL/APS/CAP/Crk-II/C3G	-0.004	0.041	-9999	-0.46	4	4
Insulin Receptor/Insulin/IRS1/NCK2	-0.063	0.17	-9999	-0.5	62	62
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.058	0.15	-9999	-0.45	64	64
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.001	0.11	-9999	-0.38	3	3
RPS6KB1	-0.004	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	0.003	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.057	0.13	-9999	-0.78	2	2
HRAS/GTP	-0.052	0.13	-9999	-0.49	4	4
Insulin Receptor	0.015	0.003	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.059	0.16	-9999	-0.47	62	62
PRKCI	-0.015	0.034	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.066	0.16	-9999	-0.42	75	75
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.004	-9999	-10000	0	0
PI3K	-0.059	0.15	-9999	-0.45	64	64
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0.004	-9999	-10000	0	0
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
AKT2	-0.015	0.16	-9999	-0.88	2	2
PRKCZ	-0.015	0.034	-9999	-10000	0	0
SH2B2	0.013	0.015	-9999	-0.31	1	1
SHC/SHIP	-0.031	0.16	-9999	-0.45	62	62
F2RL2	-0.079	0.16	-9999	-0.32	137	137
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.003	0.036	-9999	-0.47	3	3
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.003	0.033	-9999	-0.42	3	3
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	-0.004	0.044	-9999	-0.49	4	4
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.003	0.036	-9999	-0.46	3	3
INPP5D	-0.042	0.17	-9999	-0.48	62	62
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.025	0.14	-9999	-1	10	10
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.81	1	1
IRS1	-0.085	0.27	-9999	-0.81	59	59
p62DOK/RasGAP	0	0.004	-9999	-10000	0	0
INS	-0.001	0.063	-9999	-0.81	3	3
mol:PI-3-4-P2	-0.041	0.17	-9999	-0.47	62	62
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.005	0.15	-9999	-0.63	4	4
PTPRA	0.015	0.003	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.81	3	3
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0.053	-9999	-0.81	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.01	0.12	-9999	-0.33	62	62
Insulin Receptor/Insulin/IRS1	-0.064	0.17	-9999	-0.51	62	62
Insulin Receptor/Insulin/IRS3	-0.004	0.048	-9999	-0.62	3	3
Par3/Par6	-0.035	0.063	-9999	-0.46	3	3

×

Signaling events mediated by PRL

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
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0.002	0.098	-9999	-0.81	7	7
CDKN1A	-0.013	0.088	-9999	-10000	0	0
PRL-3/alpha Tubulin	-0.018	0.057	-9999	-10000	0	0
mol:Ca2+	-0.013	0.11	-9999	-0.64	10	10
AGT	-0.02	0.14	-9999	-0.45	36	36
CCNA2	-0.063	0.2	-9999	-0.58	5	5
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.11	0.26	-9999	-0.62	107	107
CDK2/Cyclin E1	0.004	0.077	-9999	-10000	0	0
MAPK3	0.004	0.064	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.004	0.064	-9999	-10000	0	0
PTP4A1	-0.072	0.21	-9999	-0.48	107	107
PTP4A3	-0.015	0.092	-9999	-0.31	44	44
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.004	0.064	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-10000	0	0
RAC1	-0.017	0.093	-9999	-0.25	17	17
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.068	0.2	-9999	-0.58	4	4
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.013	0.042	-9999	-10000	0	0
RHOC	-0.017	0.093	-9999	-0.25	17	17
RHOA	-0.017	0.093	-9999	-10000	0	0
cell motility	-0.016	0.099	-9999	-0.26	17	17
PRL-1/alpha Tubulin	-0.062	0.2	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.026	0.095	-9999	-0.67	7	7
ROCK1	-0.016	0.1	-9999	-0.26	17	17
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.072	0.21	-9999	-0.47	107	107
ATF5	0	0.064	-9999	-0.31	20	20

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.027	0.16	-9999	-0.43	66	66
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	-0.048	0.12	-9999	-0.74	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.011	0.043	-9999	-0.59	2	2
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	66	66
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.02	0.16	-9999	-0.4	66	66
AKT1	-0.003	0.15	-9999	-0.61	3	3
MAP2K1	-0.006	0.15	-9999	-0.5	6	6
MAP3K11	-0.017	0.16	-9999	-0.4	66	66
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.066	-9999	-0.63	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	0.15	-9999	-0.45	65	65
CEBPB	0.018	0.17	-9999	-0.8	6	6
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	-0.019	0.16	-9999	-0.4	66	66
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.1	0.28	-9999	-0.71	79	79
PIK3CA	0.008	0.064	-9999	-0.81	3	3
STAT1 (dimer)/PIAS1	-0.01	0.15	-9999	-0.46	6	6
CEBPB/PTGES2/Cbp/p300	-0.035	0.082	-9999	-0.44	6	6
mol:Ca2+	-0.06	0.15	-9999	-0.43	66	66
MAPK3	0.01	0.14	-9999	-0.52	6	6
STAT1 (dimer)	-0.031	0.08	-9999	-0.42	2	2
MAPK1	0.01	0.14	-9999	-0.52	6	6
JAK2	0.006	0.056	-9999	-0.84	2	2
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	0.017	0.18	-9999	-0.66	23	23
SMAD7	0.04	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.05	0.12	-9999	-0.75	1	1
PI3K	-0.056	0.14	-9999	-0.5	9	9
IFNG	-0.1	0.28	-9999	-0.72	79	79
apoptosis	0.014	0.13	-9999	-0.45	23	23
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	23	23
CAMK2B	0.005	0.083	-9999	-0.81	5	5
FRAP1	-0.001	0.14	-9999	-0.51	4	4
PRKCD	-0.002	0.15	-9999	-0.62	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	0.028	0.12	-9999	-0.53	1	1
STAT1 (dimer)/PIASy	-0.054	0.13	-9999	-0.45	7	7
SOCS1	0.001	0.074	-9999	-1.5	1	1
mol:GDP	-0.048	0.12	-9999	-0.7	1	1
CASP1	0.038	0.063	-9999	-0.35	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.042	0.057	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.054	0.13	-9999	-0.48	9	9
RAP1/GDP	-0.041	0.1	-9999	-0.6	1	1
CBL	-0.017	0.16	-9999	-0.4	66	66
MAP3K1	-0.016	0.16	-9999	-0.4	66	66
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	66	66
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-9999	-0.81	1	1
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.66	16	16
PTK2	-0.043	0.16	-9999	-0.6	32	32
positive regulation of JNK cascade	-0.023	0.085	-9999	-0.34	32	32
CDC42/GDP	0.027	0.13	-9999	-0.47	32	32
Rac1/GDP	0.029	0.13	-9999	-0.46	32	32
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	-0.028	0.1	-9999	-0.42	32	32
nectin-3/I-afadin	-0.04	0.15	-9999	-0.62	32	32
RAPGEF1	0.02	0.15	-9999	-0.53	32	32
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.17	-9999	-0.62	32	32
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.81	1	1
TLN1	0.017	0.077	-9999	-0.93	1	1
Rap1/GTP	-0.024	0.09	-9999	-0.36	32	32
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	-0.04	0.15	-9999	-0.62	32	32
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.02	0.16	-9999	-0.59	32	32
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.81	3	3
PI3K	-0.033	0.13	-9999	-0.5	33	33
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.032	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.024	0.089	-9999	-0.36	32	32
PVRL1	0.005	0.052	-9999	-0.31	13	13
PVRL3	-0.04	0.2	-9999	-0.81	32	32
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	-0.81	10	10
JAM-A/CLDN1	-0.14	0.14	-9999	-0.56	42	42
SRC	-0.047	0.18	-9999	-0.71	32	32
ITGB3	-0.012	0.14	-9999	-0.81	15	15
nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.032	-9999	-10000	0	0
FARP2	0.015	0.16	-9999	-0.57	32	32
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)	-0.035	0.13	-9999	-0.54	32	32
nectin-1/I-afadin	-0.005	0.032	-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	-0.039	0.14	-9999	-0.54	32	32
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.023	0.085	-9999	-0.34	32	32
alphaV/beta3 Integrin/Talin	0.016	0.13	-9999	-0.59	16	16
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	0.009	0.082	-9999	-0.99	1	1
VAV2	0.013	0.16	-9999	-0.59	32	32
RAP1/GDP	-0.028	0.11	-9999	-0.43	32	32
ITGAV	0.01	0.053	-9999	-0.81	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.035	0.13	-9999	-0.54	32	32
nectin-3(dimer)/I-afadin/I-afadin	-0.04	0.15	-9999	-0.62	32	32
Rac1/GTP	-0.029	0.11	-9999	-0.44	32	32
PTPRM	-0.02	0.084	-9999	-0.31	32	32
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

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0.12	-10000	0	-0.57	9	9
UGCG	-0.03	0.18	-10000	0	-0.8	25	25
AKT1/mTOR/p70S6K/Hsp90/TERT	0.019	0.13	-10000	0	-0.4	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.024	0.18	-10000	0	-0.78	25	25
mol:DAG	0	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.059	0.14	-10000	0	-0.45	37	37
FRAP1	0.002	0.2	-10000	0	-0.48	52	52
FOXO3	0.019	0.16	-10000	0	-0.59	19	19
AKT1	0.01	0.18	-10000	0	-0.56	28	28
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	0.009	0.031	-10000	0	-10000	0	0
SGMS1	0.009	0.031	-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	0.045	-10000	0	-0.56	3	3
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.003	0.16	-10000	0	-0.53	26	26
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.02	0.051	-10000	0	-0.63	3	3
RPS6KB1	0.016	0.042	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	4	4
JAK3	-0.066	0.14	-10000	0	-0.31	125	125
PIK3R1	0.015	0.005	-10000	0	-10000	0	0
JAK1	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.012	0.037	-10000	0	-0.81	1	1
MYC	0.009	0.21	-10000	0	-0.91	18	18
MYB	-0.018	0.2	-10000	0	-1.3	11	11
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	0.03	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	0.042	-10000	0	-0.5	3	3
T cell proliferation	0.017	0.15	-10000	0	-0.51	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	-0.052	17	17
PRKCZ	0.016	0.15	-10000	0	-0.53	22	22
NF kappa B1 p50/RelA	-0.057	0.14	-10000	0	-0.45	37	37
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0	0.13	-10000	0	-0.59	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.047	0.2	-10000	0	-0.81	28	28
IL2RB	-0.013	0.13	-10000	0	-0.5	27	27
TERT	-0.002	0.042	-10000	0	-0.31	9	9
E2F1	-0.005	0.078	-10000	0	-0.45	11	11
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	0.025	17	-10000	0	17
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
IL2RG	-0.046	0.19	-10000	0	-0.52	57	57
actin cytoskeleton organization	0.017	0.15	-10000	0	-0.51	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	0.065	-10000	0	-0.82	3	3
Rac1/GTP	0.031	0.042	-10000	0	-0.48	3	3
LCK	-0.008	0.11	-10000	0	-0.42	27	27
BCL2	-0.026	0.28	-10000	0	-0.82	48	48

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.34	-9999	-0.81	103	103
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.025	-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	0.04	-9999	-0.5	3	3
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.12	0.16	-9999	-0.31	204	204
ARNT/IPAS	-0.13	0.25	-9999	-0.62	103	103
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	0.087	-9999	-0.53	12	12
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.017	-9999	-10000	0	0
VHL	0.008	0.064	-9999	-0.81	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	-0.5	30	30
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.01	0.053	-9999	-0.81	2	2
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.05	-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	-0.029	0.072	-9999	-0.29	1	1

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.003	0.1	0.56	14	-10000	0	14
PI3K Class IB/PDE3B	-0.003	0.1	-10000	0	-0.56	14	14
PDE3B	-0.003	0.1	-10000	0	-0.56	14	14

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.51	35	35
ITGA4	0.002	0.077	-9999	-0.44	12	12
alpha4/beta7 Integrin	-0.033	0.12	-9999	-0.62	18	18
alpha4/beta1 Integrin	-0.007	0.055	-9999	-0.62	3	3

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.029	0.62	1	-10000	0	1
CDKN1A	-0.006	0.035	-10000	0	-10000	0	0
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
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	0.033	-10000	0	-0.31	5	5
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.019	-10000	0	-10000	0	0
PPARGC1A	-0.35	0.41	-10000	0	-0.81	219	219
FHL2	-0.05	0.22	-10000	0	-0.81	38	38
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.03	-10000	0	-0.62	1	1
HIST2H4A	0.021	0.029	-10000	0	-0.62	1	1
SIRT1/FOXO3a	0	0.026	-10000	0	-0.55	1	1
SIRT1	0	0.039	-10000	0	-0.82	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.027	-10000	0	-0.54	1	1
SIRT1/Histone H1b	-0.006	0.049	-10000	0	-0.33	10	10
apoptosis	0	0.028	0.54	1	-10000	0	1
SIRT1/PGC1A	-0.24	0.28	-10000	0	-0.55	219	219
p53/SIRT1	0.004	0.042	-10000	0	-0.62	1	1
SIRT1/FOXO4	0.001	0.027	-10000	0	-0.52	1	1
FOXO1/FHL2/SIRT1	-0.038	0.14	-10000	0	-0.5	39	39
HIST1H1E	0.015	0.053	-10000	0	-0.36	9	9
SIRT1/p300	0.001	0.03	-10000	0	-0.62	1	1
muscle cell differentiation	0.001	0.03	0.55	1	-10000	0	1
TP53	0.002	0.012	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.028	-10000	0	-0.54	1	1
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.002	0.036	-10000	0	-0.62	1	1
ACSS2	0.021	0.029	-10000	0	-0.62	1	1
SIRT1/PCAF/MYOD	-0.001	0.03	-10000	0	-0.55	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.043	0.12	0.33	1	-0.36	61	62
FRAP1	0.008	0.027	-10000	0	-10000	0	0
AKT1	-0.009	0.11	0.24	1	-0.3	61	62
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.042	-10000	0	-0.55	3	3
mol:GTP	-0.028	0.077	-10000	0	-0.5	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.008	0.022	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.023	0.066	-10000	0	-0.45	3	3
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.035	0.14	-10000	0	-0.42	59	59
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	0.009	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	2	-0.002	58	60
EIF4B	0.017	0.055	-10000	0	-0.34	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.014	0.039	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.025	0.14	-10000	0	-0.39	61	61
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.04	0.18	1	-0.28	2	3
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.023	0.065	-10000	0	-0.44	3	3
mol:Amino Acids	0	0.001	0.001	2	-0.002	58	60
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.041	0.12	0.26	1	-0.33	61	62
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	58	-0.001	2	60
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	-0.046	0.15	-10000	0	-0.46	59	59
INS	-0.005	0.063	-10000	0	-0.81	3	3
PTEN	0.011	0.037	-10000	0	-0.81	1	1
PDK2	-0.039	0.11	0.26	1	-0.32	61	62
EIF4EBP1	0.012	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
PPP2R5D	0.015	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.015	0.04	-10000	0	-0.49	3	3
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	0.015	0.04	-10000	0	-0.5	3	3
eIF4E/4E-BP1	0.019	0.008	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.035	0.14	-10000	0	-0.62	28	28
ATM	0.012	0.037	-10000	0	-0.81	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.012	0.037	-10000	0	-0.81	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.029	-10000	0	-0.44	2	2
protein ubiquitination	-0.027	0.11	-10000	0	-0.45	29	29
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	-0.003	0.042	-10000	0	-0.54	3	3
MRE11A	0.008	0.064	-10000	0	-0.81	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	-0.035	0.14	-10000	0	-0.62	28	28
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	0.065	-10000	0	-0.31	21	21
DNA repair	0.051	0.1	-10000	0	-0.46	2	2
BRCA1/BARD1/ubiquitin	-0.035	0.14	-10000	0	-0.62	28	28
BARD1/DNA-PK	-0.028	0.11	-10000	0	-0.49	28	28
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.035	0.14	0.62	28	-10000	0	28
BRCA1/BARD1/CTIP/M/R/N Complex	0.019	0.092	-10000	0	-0.57	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.031	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/P53	-0.029	0.12	-10000	0	-0.49	29	29
BARD1/CSTF1/BRCA1	-0.031	0.12	-10000	0	-0.54	28	28
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.034	0.19	-10000	0	-0.81	28	28
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.031	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/UbcH7	-0.031	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/RAD51/PCNA	-0.029	0.12	-10000	0	-0.49	28	28
BARD1/DNA-PK/P53	-0.026	0.11	-10000	0	-0.46	28	28
BRCA1/BARD1/Ubiquitin	-0.035	0.14	-10000	0	-0.62	28	28
BRCA1/BARD1/CTIP	-0.029	0.12	-10000	0	-0.49	29	29
FA complex	0.038	0.024	-10000	0	-10000	0	0
BARD1/EWS	-0.035	0.14	-10000	0	-0.62	28	28
RBBP8	0.023	0.029	-10000	0	-0.62	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	0.029	0.11	0.49	29	-10000	0	29
BRCA1/BARD1	-0.027	0.11	-10000	0	-0.46	29	29
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.036	0.15	-10000	0	-0.63	28	28
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.011	0.025	-10000	0	-0.31	3	3
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.035	0.14	-10000	0	-0.62	28	28
EWSR1	0.013	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.003	0.12	-10000	0	-0.81	10	10
ANTXR2	0.008	0.064	-10000	0	-0.81	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.016	-10000	0	-0.1	13	13
monocyte activation	-0.046	0.17	-10000	0	-0.48	60	60
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	0.074	-10000	0	-0.49	11	11
CYAA	0.003	0.079	-10000	0	-0.48	13	13
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.019	0.12	-10000	0	-0.46	35	35
Channel	-0.013	0.081	-10000	0	-0.5	13	13
NLRP1	-0.004	0.034	-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	0.016	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	-0.022	0.083	-10000	0	-0.25	40	40
PA/Cellular Receptors	-0.014	0.088	-10000	0	-0.55	13	13
apoptosis	-0.003	0.016	-10000	0	-0.1	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.078	-10000	0	-0.47	13	13
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.087	0.26	-10000	0	-0.76	64	64
VCAM1	-0.046	0.17	-10000	0	-0.48	60	60
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.024	0.1	11	-10000	0	11
IL18	-0.01	0.085	-10000	0	-0.41	14	14
negative regulation of macrophage activation	-0.003	0.016	-10000	0	-0.1	13	13
LEF	-0.003	0.016	-10000	0	-0.1	13	13
CASP1	-0.003	0.02	-10000	0	-0.22	2	2
mol:cAMP	-0.003	0.019	-10000	0	-10000	0	0
necrosis	-0.003	0.016	-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	0.077	-10000	0	-0.48	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.081	-9999	-0.71	6	6
PDGFRB	0.012	0.037	-9999	-0.82	1	1
SPHK1	-0.008	0.021	-9999	-10000	0	0
mol:S1P	-0.009	0.025	-9999	-10000	0	0
S1P1/S1P/Gi	0.015	0.14	-9999	-0.38	51	51
GNAO1	-0.017	0.15	-9999	-0.7	21	21
PDGFB-D/PDGFRB/PLCgamma1	0.025	0.13	-9999	-0.54	10	10
PLCG1	0.022	0.14	-9999	-0.35	50	50
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.81	1	1
GNAI2	0.014	0.004	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.011	0.073	-9999	-0.62	6	6
S1P1/S1P	-0.016	0.066	-9999	-0.5	6	6
negative regulation of cAMP metabolic process	0.016	0.14	-9999	-0.37	51	51
MAPK3	0.009	0.19	-9999	-0.57	41	41
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	0.006	0.074	-9999	-0.82	4	4
PLCB2	0.03	0.072	-9999	-0.43	6	6
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.054	-9999	-0.41	6	6
receptor internalization	-0.015	0.061	-9999	-0.46	6	6
PTGS2	-0.03	0.33	-9999	-1.1	41	41
Rac1/GTP	-0.013	0.054	-9999	-0.41	6	6
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.064	-9999	-0.81	3	3
negative regulation of T cell proliferation	0.016	0.14	-9999	-0.37	51	51
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.005	-9999	-10000	0	0
MAPK1	0.009	0.19	-9999	-0.57	41	41
S1P1/S1P/PDGFB-D/PDGFRB	0.032	0.086	-9999	-0.49	7	7
ABCC1	0.014	0.002	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.012	0.037	-9999	-0.81	1	1
Caspase 8 (4 units)	-0.022	0.063	-9999	-10000	0	0
NEF	-0.013	0.056	-9999	-10000	0	0
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	-0.005	0.2	-9999	-0.8	26	26
CYCS	-0.004	0.1	-9999	-0.39	7	7
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.039	0.19	-9999	-0.78	25	25
MAP2K7	0.023	0.081	-9999	-0.31	2	2
protein ubiquitination	0.039	0.086	-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	0.11	-9999	-0.42	7	7
NF-kappa-B/RelA/I kappa B alpha	-0.022	0.08	-9999	-0.34	26	26
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.012	0.037	-9999	-0.81	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	0.08	-9999	-0.35	26	26
MAPK8	0.02	0.1	-9999	-0.41	11	11
APAF1	0.012	0.037	-9999	-0.81	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	0.008	0.098	-9999	-0.31	30	30
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.1	-9999	-0.39	3	3
CHUK	0.039	0.091	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.021	-9999	-0.46	1	1
TCRz/NEF	-0.062	0.18	-9999	-0.52	54	54
TNF	-0.087	0.26	-9999	-0.76	64	64
FASLG	-0.074	0.29	-9999	-0.85	54	54
NFKB1	0.007	0.047	-9999	-0.81	1	1
TNFR1A/BAG4/TNF-alpha	-0.065	0.17	-9999	-0.54	58	58
CASP6	-0.006	0.045	-9999	-10000	0	0
CASP7	0.028	0.16	-9999	-0.62	25	25
RELA	0.009	0.029	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.028	0.16	-9999	-0.62	25	25
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.028	-9999	-0.62	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.098	-9999	-0.37	2	2
APAF-1/Caspase 9	-0.047	0.12	-9999	-0.52	25	25
BCL2	-0.004	0.15	-9999	-0.4	44	44

×

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	0.07	0.009	-9999	-10000	0	0
EGFR	0.005	0.083	-9999	-0.81	5	5
EPHA2	0.011	0.025	-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	26	26
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	-0.037	0.073	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	78	78
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.072	0.19	-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	0.048	0.034	-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	-0.067	0.15	-9999	-0.42	77	77
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	-0.79	119	119
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	0.047	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.04	0.06	-9999	-0.42	8	8
Ephrin A1/EPHA2	-0.001	0.007	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.037	0.074	-9999	-10000	0	0
HGF/MET	-0.099	0.16	-9999	-0.46	74	74
HGF	-0.11	0.3	-9999	-0.81	74	74
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.033	0	-9999	-10000	0	0
actin cable formation	0.085	0.021	-9999	-10000	0	0
KIAA1543	0.047	0.021	-9999	-0.41	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	0.019	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.097	0.18	-9999	-0.42	113	113
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.1	0.16	-9999	-0.31	179	179
PLEKHA7	0.04	0.022	-9999	-0.44	1	1
mol:GTP	-0.001	0.01	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.066	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

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.024	0.095	-9999	-10000	0	0
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.28	0.45	-9999	-0.92	151	151
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	-0.001	0.069	-9999	-0.29	23	23
ER alpha/Oestrogen	-0.041	0.14	-9999	-0.58	26	26
NFX1/SIN3/HDAC complex	0.047	0.026	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	78	78
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	0.072	-9999	-10000	0	0
SAP18	0.014	0	-9999	-10000	0	0
MRN complex	-0.003	0.042	-9999	-0.54	3	3
WT1	-0.025	0.1	-9999	-0.31	54	54
WRN	0.012	0.037	-9999	-0.81	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	-0.03	0.056	-9999	-10000	0	0
Mad/Max	0.006	0.01	-9999	-10000	0	0
TERT	-0.024	0.096	-9999	-10000	0	0
CCND1	-0.016	0.095	-9999	-10000	0	0
MAX	0.014	0.002	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
RBBP4	0.009	0.064	-9999	-0.81	3	3
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
Telomerase/911	0.036	0.019	-9999	-10000	0	0
CDKN1B	-0.039	0.19	-9999	-0.52	64	64
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	0.037	-9999	-0.81	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.001	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.81	112	112
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.006	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.81	127	127
IFN-gamma/IRF1	-0.085	0.2	-9999	-0.6	65	65
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.013	0.015	-9999	-0.31	1	1
Telomerase	0.013	0.074	-9999	-0.48	6	6
IRF1	0.018	0.015	-9999	-0.3	1	1
ESR1	-0.046	0.19	-9999	-0.52	55	55
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.025	-9999	-0.55	1	1
ubiquitin-dependent protein catabolic process	0.052	0.027	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.052	0.027	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC2	0.014	0.003	-9999	-10000	0	0
ATM	-0.001	0.025	-9999	-0.56	1	1
SMAD3	0.02	0.028	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.014	0.002	-9999	-10000	0	0
MRE11A	0.008	0.064	-9999	-0.81	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	-0.032	0.067	-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	0.041	-9999	-0.31	8	8
NFKB1	0.012	0.037	-9999	-0.81	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	0.025	-9999	-0.56	1	1
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.005	0.083	-9999	-0.82	5	5
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.1	0.23	-9999	-0.62	77	77
MYC	-0.006	0.13	-9999	-0.81	12	12
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	0.041	-9999	-0.31	8	8
TRF2/BLM	0	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.015	0.084	-9999	-10000	0	0
SP1/HDAC2	0.023	0.005	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.03	0.056	-9999	-10000	0	0
Smad3/Myc	0.011	0.091	-9999	-0.55	12	12
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.099	0.28	-9999	-0.8	64	64
Telomerase/PinX1	-0.03	0.056	-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	-0.03	0.056	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.003	0.035	-9999	-0.45	3	3
TRF2/WRN	-0.001	0.027	-9999	-0.59	1	1
Telomerase/hnRNP C1/C2	-0.03	0.056	-9999	-10000	0	0
E2F1	-0.085	0.15	-9999	-0.31	151	151
ZNFX1	0.014	0	-9999	-10000	0	0
PIF1	0.001	0.095	-9999	-0.61	10	10
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

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-9999	-0.81	1	1
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.057	-9999	-0.27	17	17
GNAO1	-0.015	0.15	-9999	-0.69	21	21
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.005	0.028	-9999	-0.47	1	1
AKT3	0.049	0.049	-9999	-0.56	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.81	1	1
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.013	0.037	-9999	-0.81	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.01	0.032	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.036	0.066	-9999	-0.31	17	17
MAPK3	0.042	0.063	-9999	-0.29	16	16
MAPK1	0.042	0.063	-9999	-0.29	16	16
JAK2	0.045	0.065	-9999	-0.29	16	16
CXCR4	0.041	0.064	-9999	-0.29	16	16
FLT1	0.015	0.037	-9999	-0.81	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.042	0.063	-9999	-10000	0	0
S1P/S1P3/Gi	0.036	0.067	-9999	-0.31	17	17
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.01	0.051	-9999	-0.28	16	16
VEGFA	0.012	0.064	-9999	-0.81	3	3
S1P/S1P2/Gi	0.03	0.067	-9999	-0.32	17	17
VEGFR1 homodimer/VEGFA homodimer	0.024	0.066	-9999	-0.79	3	3
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.068	0.17	-9999	-0.35	125	125
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	-0.81	118	118
GNA15	-0.011	0.09	-9999	-0.32	36	36
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.12	-9999	-0.81	10	10
Rac1/GTP	-0.01	0.051	-9999	-0.28	16	16

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.046	0.059	-10000	0	-0.38	9	9
NFATC2	-0.02	0.097	-10000	0	-0.3	29	29
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	0.014	0.088	-10000	0	-0.32	22	22
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	-0.024	0.089	-10000	0	-0.53	9	9
BCL2/BAX	-0.046	0.16	-10000	0	-0.62	36	36
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	0.012	0.021	-10000	0	-0.31	2	2
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.018	0.084	-10000	0	-0.56	4	4
Calcineurin A alpha-beta B1/BCL2	-0.047	0.22	-10000	0	-0.81	36	36
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.018	0.082	0.55	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	-0.33	312	312
MAP3K8	-0.002	0.098	-10000	0	-0.82	7	7
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.12	0.16	-10000	0	-0.49	24	24
CABIN1	0.014	0.089	-10000	0	-0.32	22	22
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	-0.004	0.11	-10000	0	-0.53	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	-0.009	0.12	-10000	0	-0.82	11	11
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	-0.007	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	0.05	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.049	-10000	0	-10000	0	0
PRKCB	-0.022	0.12	-10000	0	-0.36	46	46
PRKCE	0.005	0.083	-10000	0	-0.81	5	5
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	-0.018	0.16	-10000	0	-0.81	19	19
PRKCG	0.005	0.025	-10000	0	-0.31	3	3
PRKCQ	0.003	0.091	-10000	0	-0.81	6	6
FKBP38/BCL2	-0.045	0.16	-10000	0	-0.62	36	36
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	0.031	0.089	-10000	0	-0.38	19	19
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	-0.011	0.07	-10000	0	-0.56	7	7
NFATc/ERK1	0.052	0.056	-10000	0	-0.35	8	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.023	0.088	-10000	0	-0.52	9	9
NR4A1	-0.19	0.36	-10000	0	-0.73	148	148
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	0.064	-10000	0	-0.39	5	5
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	0.061	-10000	0	-0.36	8	8
CREBBP	0.01	0.007	-10000	0	-10000	0	0
BCL2	-0.047	0.22	-10000	0	-0.81	36	36

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.017	0.093	-10000	0	-0.46	13	13
ACTA1	0.008	0.12	-10000	0	-0.62	11	11
NUMA1	0.017	0.093	-10000	0	-0.46	13	13
SPTAN1	0.013	0.12	-10000	0	-0.62	11	11
LIMK1	0.013	0.12	-10000	0	-0.62	11	11
BIRC3	-0.036	0.19	-10000	0	-0.65	37	37
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
CASP10	-0.003	0.12	-10000	0	-0.65	13	13
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	0.017	0.093	-10000	0	-0.46	13	13
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.013	0.12	-10000	0	-0.6	11	11
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	0.013	0.12	-10000	0	-0.62	11	11
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.055	0.22	-10000	0	-0.65	59	59
BID	-0.01	0.069	-10000	0	-0.31	13	13
MAP3K1	0.013	0.043	-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	0.029	-10000	0	-0.62	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.01	0.12	-10000	0	-0.6	12	12
CASP9	0.013	0	-10000	0	-10000	0	0
DNA repair	-0.015	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	0.019	0.11	-10000	0	-0.59	11	11
APAF1	0.012	0.037	-10000	0	-0.81	1	1
CASP6	0.021	0.064	-10000	0	-0.49	2	2
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.02	0.11	-10000	0	-0.59	11	11
CASP7	0.01	0.08	0.34	25	-10000	0	25
KRT18	0.016	0.018	-10000	0	-10000	0	0
apoptosis	0.024	0.11	-10000	0	-0.55	13	13
DFFA	0.013	0.12	-10000	0	-0.62	11	11
DFFB	0.013	0.12	-10000	0	-0.62	11	11
PARP1	0.015	0.052	0.23	22	-0.18	1	23
actin filament polymerization	-0.02	0.11	0.56	11	-10000	0	11
TNF	-0.087	0.26	-10000	0	-0.76	64	64
CYCS	0.004	0.047	-10000	0	-0.22	13	13
SATB1	0.028	0.061	-10000	0	-0.46	2	2
SLK	0.01	0.13	-10000	0	-0.65	13	13
p15 BID/BAX	-0.002	0.062	-10000	0	-0.34	5	5
CASP2	0.007	0.11	-10000	0	-0.46	11	11
JNK cascade	-0.013	0.042	0.23	3	-10000	0	3
CASP3	0.005	0.12	-10000	0	-0.61	13	13
LMNB2	0.021	0.075	-10000	0	-0.33	3	3
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.49	25	25
negative regulation of DNA binding	-0.054	0.22	-10000	0	-0.64	59	59
stress fiber formation	0.01	0.13	-10000	0	-0.63	13	13
GZMB	-0.017	0.14	-10000	0	-0.68	16	16
CASP1	0.015	0.032	-10000	0	-0.45	2	2
LMNB1	0.02	0.075	-10000	0	-0.36	2	2
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	0.02	0.1	-10000	0	-0.5	11	11
LMNA	0.021	0.075	-10000	0	-0.33	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.002	0.12	-10000	0	-0.49	11	11
LRDD	0.013	0	-10000	0	-10000	0	0
SREBF1	0.012	0.12	-10000	0	-0.62	11	11
APAF-1/Caspase 9	0.004	0.041	-10000	0	-0.39	1	1
nuclear fragmentation during apoptosis	0.017	0.092	-10000	0	-0.45	13	13
CFL2	0.02	0.11	-10000	0	-0.58	11	11
GAS2	0.007	0.13	-10000	0	-0.58	17	17
positive regulation of apoptosis	0.023	0.078	-10000	0	-0.36	2	2
PRF1	-0.004	0.11	-10000	0	-0.69	12	12

×

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	0.05	-9999	-0.31	12	12
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.022	0.017	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.69	21	21
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	0.032	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.011	-9999	-10000	0	0
S1PR5	0.007	0.053	-9999	-0.37	8	8
S1PR4	0.009	0.038	-9999	-0.31	7	7
GNAI1	0.012	0.037	-9999	-0.81	1	1
S1P/S1P5/G12	-0.004	0.028	-9999	-0.48	1	1
S1P/S1P3/Gq	-0.051	0.16	-9999	-0.41	25	25
S1P/S1P4/Gi	0.03	0.067	-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	-0.81	118	118
GNA15	-0.011	0.09	-9999	-0.32	36	36
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.12	-9999	-0.81	10	10
ABCC1	0.013	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.061	-10000	0	-0.34	7	7
KAT2B	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
AKT1	0.012	0.086	0.24	6	-0.41	15	21
RAR alpha/9cRA/Cyclin H	-0.021	0.087	-10000	0	-0.41	19	19
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.068	-10000	0	-0.37	8	8
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.015	0.12	-10000	0	-0.42	28	28
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0.009	-10000	0	-0.21	1	1
RXRs/RARs/NRIP1/9cRA	-0.016	0.15	-10000	0	-0.62	24	24
NCOA2	-0.067	0.24	-10000	0	-0.81	48	48
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	-0.004	0.12	-10000	0	-0.81	11	11
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.033	0.13	-10000	0	-0.66	19	19
RARA	0.008	0.088	-10000	0	-0.33	28	28
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.002	0.14	-10000	0	-0.57	17	17
PRKCA	-0.015	0.16	-10000	0	-0.81	19	19
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.027	0.15	-10000	0	-0.64	24	24
RXRG	-0.11	0.1	-10000	0	-0.52	23	23
RXRA	0.014	0.088	-10000	0	-0.33	28	28
RXRB	0.008	0.091	-10000	0	-0.44	19	19
VDR/Vit D3/DNA	0	0.009	-10000	0	-0.21	1	1
RBP1	-0.003	0.11	-10000	0	-0.65	12	12
CRBP1/9-cic-RA	-0.012	0.082	-10000	0	-0.63	8	8
RARB	-0.008	0.14	-10000	0	-0.81	14	14
PRKCG	0.008	0.026	-10000	0	-0.31	3	3
MNAT1	0.013	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.022	0.16	-10000	0	-0.66	24	24
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.005	0.13	-10000	0	-0.54	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.087	-10000	0	-0.48	8	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.027	0.15	-10000	0	-0.64	24	24
positive regulation of DNA binding	-0.02	0.082	-10000	0	-0.39	19	19
NRIP1	-0.023	0.14	-10000	0	-0.64	16	16
RXRs/RARs	-0.034	0.15	-10000	0	-0.63	24	24
RXRs/RXRs/DNA/9cRA	-0.044	0.13	-10000	0	-0.68	19	19
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	0.052	-10000	0	-0.52	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

×

Class I PI3K signaling events mediated by Akt

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
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	-10000	0	0
CDKN1A	0.034	0.029	-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	0.014	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
AKT3	0.016	0.029	-10000	0	-0.44	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	0.023	-10000	0	-0.42	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.012	0.037	-10000	0	-0.81	1	1
RAF1	0.013	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.022	0.41	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	0.016	-10000	0	-10000	0	0
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	-0.054	0.2	-10000	0	-0.54	69	69
MAP3K5	0.012	0.037	-10000	0	-0.81	1	1
MAPKAP1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.036	-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	-0.002	0.035	-10000	0	-0.54	2	2
YWHAE	0.013	0	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.004	0.028	-10000	0	-0.36	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	-0.5	1	1
AKT2	0.016	0.029	-10000	0	-0.44	2	2
FOXO1-3a-4/14-3-3 family	0.025	0.042	-10000	0	-10000	0	0
PDPK1	0.01	0.053	-10000	0	-0.81	2	2
MDM2	0.039	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.015	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.051	0.015	-10000	0	-10000	0	0
TSC1/TSC2	0.045	0.015	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.011	-10000	0	-10000	0	0
glucose import	-0.062	0.21	-10000	0	-0.52	84	84
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	-0.063	0.22	-10000	0	-0.52	84	84
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	-0.33	312	312
G1/S transition of mitotic cell cycle	0.046	0.015	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.001	0.053	-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

×

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	0.006	0.076	-9999	-0.71	5	5
positive regulation of NF-kappaB transcription factor activity	-0.005	0.056	-9999	-0.62	4	4
MAP2K4	0.047	0.034	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.008	0.064	-9999	-0.81	3	3
SMPD1	-0.002	0.026	-9999	-0.29	4	4
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	-0.005	0.057	-9999	-0.62	4	4
TRAIL/TRAILR3	-0.059	0.1	-9999	-0.66	4	4
TRAIL/TRAILR1	-0.009	0.074	-9999	-0.62	7	7
TRAIL/TRAILR4	-0.005	0.057	-9999	-0.62	4	4
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.059	-9999	-0.5	7	7
IKK complex	-0.002	0.019	-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	0.019	0.059	-9999	-0.62	4	4
MAP3K1	-0.004	0.031	-9999	-0.32	4	4
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.064	-9999	-0.81	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.034	0.043	-9999	-0.33	7	7
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.019	0.059	-9999	-0.62	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.007	0.054	-9999	-0.46	7	7
mol:ceramide	0.018	0.028	-9999	-0.29	4	4
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.042	0.082	-9999	-0.46	11	11
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.074	0.14	-9999	-0.31	133	133
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.008	0.064	-9999	-0.54	7	7
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.006	0.051	-9999	-0.51	4	4
JNK cascade	-0.005	0.056	-9999	-0.62	4	4
TRAIL (trimer)	0.006	0.075	-9999	-0.71	5	5
TNFRSF10C	-0.074	0.14	-9999	-0.31	133	133
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.007	0.055	-9999	-0.46	7	7
TRAIL/TRAILR2/FADD	-0.005	0.049	-9999	-0.54	4	4
cell death	0.018	0.028	-9999	-0.29	4	4
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.036	0.033	-9999	-0.33	4	4
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.015	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.004	0.041	-9999	-0.46	4	4

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.006	0.13	-10000	0	-0.56	11	11
BAG4	0.012	0.037	-10000	0	-0.81	1	1
BAD	0.018	0.045	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.65	37	37
BAX	0.017	0.047	-10000	0	-0.22	1	1
EnzymeConsortium:3.1.4.12	0.004	0.033	-10000	0	-0.12	11	11
IKBKB	0.014	0.12	-10000	0	-0.52	11	11
MAP2K2	0.027	0.056	-10000	0	-0.36	2	2
MAP2K1	0.027	0.056	-10000	0	-0.36	2	2
SMPD1	0.01	0.033	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.014	0.12	-10000	0	-0.53	11	11
MAP2K4	0.024	0.046	-10000	0	-10000	0	0
protein ubiquitination	0.015	0.12	-10000	0	-0.52	11	11
EnzymeConsortium:2.7.1.37	0.031	0.061	-10000	0	-0.37	2	2
response to UV	0	0.001	-10000	0	-0.003	2	2
RAF1	0.022	0.056	-10000	0	-0.39	2	2
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.047	-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	0.018	0.047	-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	0.055	-10000	0	-0.35	2	2
MAPK1	0.03	0.055	-10000	0	-0.35	2	2
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.006	0.13	-10000	0	-0.56	11	11
KSR1	0.016	0.056	-10000	0	-0.42	2	2
MAPK8	0.021	0.08	-10000	0	-0.42	11	11
TRAF2	0.013	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.014	0.12	-10000	0	-0.52	11	11
TNF R/SODD	-0.001	0.028	-10000	0	-0.62	1	1
TNF	-0.087	0.27	-10000	0	-0.76	64	64
CYCS	0.027	0.056	0.16	30	-10000	0	30
IKBKG	0.014	0.12	-10000	0	-0.52	11	11
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.003	0.13	-10000	0	-0.44	25	25
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AIFM1	0.027	0.056	0.16	30	-10000	0	30
TNF/TNF R/SODD	-0.065	0.17	-10000	0	-0.54	58	58
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.033	-10000	0	-10000	0	0
NSMAF	0.006	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	-0.81	36	36

×

Canonical NF-kappaB 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	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	0.073	0.051	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	-0.029	0.078	-9999	-0.62	2	2
NFKBIA	0.048	0.023	-9999	-0.47	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	0.02	-9999	-10000	0	0
IKK complex/A20	-0.048	0.13	-9999	-0.39	57	57
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.038	-9999	-0.42	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	0.034	-9999	-0.54	2	2
NOD2	-0.033	0.12	-9999	-0.32	68	68
NFKB1	0.015	0.037	-9999	-0.81	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	0.037	-9999	-0.81	1	1
TNF/TNFR1A	-0.075	0.2	-9999	-0.62	57	57
TRAF6	0.01	0.053	-9999	-0.81	2	2
PRKCA	-0.018	0.16	-9999	-0.81	19	19
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.087	0.26	-9999	-0.76	64	64
NF kappa B1 p50/RelA	-0.001	0.023	-9999	-0.52	1	1
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.023	-9999	-0.46	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	-0.016	0.076	-9999	-0.39	19	19

×

Canonical Wnt signaling pathway

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
HDAC1	0.006	0.023	0.22	1	-10000	0	1
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	-0.024	0.16	-10000	0	-0.65	28	28
TLE1	0	0.065	-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	60	60
beta catenin/RanBP3	0.021	0.09	0.36	27	-10000	0	27
KREMEN2	-0.01	0.083	-10000	0	-0.31	35	35
DKK1	-0.041	0.13	-10000	0	-0.32	80	80
beta catenin/beta TrCP1	0.052	0.037	-10000	0	-10000	0	0
FZD1	0.014	0.001	-10000	0	-10000	0	0
AXIN2	-0.048	0.31	-10000	0	-1.6	19	19
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	0.064	0.044	0.29	1	-0.4	1	2
Axin1/APC/GSK3	0.007	0.031	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.058	0.021	-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	-0.028	0.25	-10000	0	-1.6	12	12
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.034	0.11	-10000	0	-0.55	19	19
NKD1	-0.013	0.14	-10000	0	-0.7	18	18
TCF4	0.006	0.021	-10000	0	-10000	0	0
TCF3	0.006	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.001	0.013	-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	-0.003	0.066	-10000	0	-0.4	10	10
DVL1	0.019	0.027	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.067	0.074	-10000	0	-0.49	3	3
DKK1/LRP6/Kremen 2	-0.038	0.08	-10000	0	-0.39	9	9
LRP6	0.014	0	-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	-0.8	1	1
WNT1	0.008	0.032	-10000	0	-0.31	5	5
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	0.059	0.36	14	-10000	0	14
APC	0.038	0.028	-10000	0	-0.46	1	1
WNT1/LRP6/FZD1	0.034	0.037	-10000	0	-10000	0	0
CREBBP	0.006	0.021	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.033	0.3	1	-0.46	2	3
DAPP1	-0.054	0.14	-10000	0	-0.49	12	12
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.059	0.18	-10000	0	-0.49	32	32
mol:DAG	-0.006	0.097	-10000	0	-0.27	16	16
HRAS	0.013	0.02	-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	0.013	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	0.037	-10000	0	-0.81	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	0.029	-10000	0	-0.31	4	4
mol:Ca2+	0.006	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.81	1	1
ZAP70	-0.026	0.16	-10000	0	-0.62	31	31
mol:IP3	0.004	0.072	-10000	0	-0.21	1	1
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	-0.002	0.035	-10000	0	-0.54	2	2
BLNK	0.013	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.038	0.037	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-10000	0	0
PLEKHA2	0.022	0.041	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.79	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.014	0.3	1	-10000	0	1
RhoA/GTP	0	0.013	0.26	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.051	0.16	-10000	0	-0.59	14	14
BLK	-0.24	0.37	-10000	0	-0.74	168	168
PDPK1	0.01	0.053	-10000	0	-0.81	2	2
CYTH1	0	0.013	0.26	1	-10000	0	1
HCK	-0.01	0.084	-10000	0	-0.31	36	36
CYTH3	-0.002	0.033	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	-0.012	0.086	0.22	1	-0.59	10	11
SGK1	-0.013	0.096	0.24	1	-0.66	10	11
INPP5D	-0.003	0.071	-10000	0	-0.31	25	25
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	0.019	0.29	1	-10000	0	1
mol:PI-3-4-5-P3	0	0.017	0.36	1	-10000	0	1
ARAP3/RAP1A/GTP	0	0.013	0.26	1	-10000	0	1
VAV1	-0.015	0.1	-10000	0	-0.35	39	39
mol:PI-3-4-P2	0.013	0.049	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.032	0.009	-10000	0	-10000	0	0
PLEKHA1	0.022	0.041	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.035	-10000	0	-0.46	1	1
LAT	0.005	0.077	-10000	0	-0.65	6	6
Rac1/GTP	-0.006	0.054	-10000	0	-0.47	2	2
ITK	-0.056	0.14	-10000	0	-0.43	61	61
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.015	0.13	-10000	0	-0.4	16	16
LCK	-0.01	0.11	-10000	0	-0.42	27	27
BTK	-0.013	0.06	0.26	1	-0.43	8	9

×

Circadian rhythm 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
chromatin modification	-0.025	0.047	-9999	-0.62	1	1
CLOCK	-0.044	0.21	-9999	-0.82	33	33
TIMELESS/CRY2	-0.004	0.065	-9999	-10000	0	0
DEC1/BMAL1	-0.024	0.067	-9999	-10000	0	0
ATR	0.012	0.037	-9999	-0.81	1	1
NR1D1	-0.054	0.13	-9999	-10000	0	0
ARNTL	-0.025	0.1	-9999	-0.31	55	55
TIMELESS	-0.012	0.073	-9999	-10000	0	0
NPAS2	0.009	0.04	-9999	-0.81	1	1
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.006	0.03	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.006	0.03	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.035	0.16	-9999	-0.56	34	34
BMAL1/CLOCK	-0.055	0.16	-9999	-0.62	15	15
S phase of mitotic cell cycle	-0.025	0.047	-9999	-0.62	1	1
TIMELESS/CHEK1/ATR	-0.025	0.048	-9999	-0.64	1	1
mol:NADPH	-0.006	0.03	-9999	-10000	0	0
PER1/TIMELESS	-0.004	0.065	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.014	-9999	-0.31	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.008	0.094	-9999	-0.45	17	17
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.007	0.074	-9999	-0.81	4	4
ITGA4	0.002	0.077	-9999	-0.44	12	12
alpha4/beta7 Integrin/MAdCAM1	-0.035	0.11	-9999	-0.5	20	20
EPO	0.002	0.038	-9999	-0.31	7	7
alpha4/beta7 Integrin	-0.033	0.12	-9999	-0.62	18	18
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.007	0.055	-9999	-0.62	3	3
EPO/EPOR (dimer)	-0.007	0.036	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.037	-9999	-0.46	3	3
PIK3CA	0.008	0.064	-9999	-0.81	3	3
PI3K	-0.004	0.048	-9999	-0.62	3	3
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.022	0.067	-9999	-0.62	4	4
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.012	0.096	-9999	-0.36	30	30
cell adhesion	-0.035	0.1	-9999	-0.49	20	20
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.022	0.078	-9999	-0.55	7	7
ITGB7	-0.024	0.15	-9999	-0.51	35	35
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.013	0.08	-9999	-0.55	9	9
p130Cas/Crk/Dock1	0.039	0.079	-9999	-0.81	1	1
VCAM1	0.002	0.089	-9999	-0.56	10	10
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.042	-9999	-0.49	3	3
BCAR1	0.031	0.074	-9999	-0.51	7	7
EPOR	0.007	0.046	-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	-0.001	0.038	-9999	-0.48	3	3

×

FoxO family signaling

Figure S107. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S107. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.038	0.025	-9999	-10000	0	0
PLK1	0.1	0.11	-9999	-0.73	1	1
CDKN1B	0.15	0.047	-9999	-0.39	1	1
FOXO3	0.1	0.11	-9999	-0.58	4	4
KAT2B	0.025	0.01	-9999	-10000	0	0
FOXO1/SIRT1	0.01	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	0.016	-9999	-10000	0	0
MAPK10	0.043	0.025	-9999	-0.5	1	1
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.11	0.065	-9999	-0.48	4	4
response to oxidative stress	0.015	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	0.013	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	0.04	0.028	-9999	-10000	0	0
FOXO1/SKP2	0.039	0.05	-9999	-0.49	4	4
mol:GDP	0.015	0.013	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.061	-9999	-0.72	1	1
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.041	0.042	-9999	-10000	0	0
MST1	0.023	0.042	-9999	-0.57	2	2
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.008	0.066	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.033	0.077	-9999	-0.48	11	11
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	0.006	0.042	-9999	-0.81	1	1
SOD2	0.16	0.073	-9999	-0.53	3	3
RBL2	0.11	0.15	-9999	-1.4	4	4
RAL/GDP	0.033	0.013	-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	0.042	0.01	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.082	0.42	-9999	-1.5	38	38
SKP2	0.007	0.074	-9999	-0.81	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	0.049	-9999	-0.42	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.05	-9999	-0.49	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.008	0.12	-9999	-0.81	10	10
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.003	-9999	-10000	0	0
ZFAND5	0.11	0.055	-9999	-0.47	1	1
SFN	-0.21	0.19	-9999	-0.33	312	312
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.016	0.065	-9999	-10000	0	0
CREBBP	0.014	0.003	-9999	-10000	0	0
FBXO32	0.1	0.11	-9999	-0.73	1	1
BCL6	0.11	0.11	-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

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.69	21	21
CDC42/GTP	-0.011	0.054	-9999	-0.29	17	17
PLCG1	0.03	0.064	-9999	-0.3	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	0.053	-9999	-0.29	17	17
S1PR5	0.007	0.053	-9999	-0.37	8	8
S1PR4	0.009	0.038	-9999	-0.31	7	7
MAPK3	0.03	0.064	-9999	-0.3	17	17
MAPK1	0.03	0.064	-9999	-0.3	17	17
S1P/S1P5/Gi	0.022	0.07	-9999	-0.33	18	18
GNAI1	0.012	0.037	-9999	-0.81	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.003	0.031	-9999	-0.55	1	1
RHOA	0.032	0.018	-9999	-10000	0	0
S1P/S1P4/Gi	0.022	0.068	-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	-0.002	0.016	-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

×

S1P5 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	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	0.011	0.054	0.29	17	-10000	0	17
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.003	0.031	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.017	0.15	-10000	0	-0.69	21	21
RhoA/GTP	-0.012	0.055	-10000	0	-0.3	17	17
negative regulation of cAMP metabolic process	0.022	0.07	-10000	0	-0.33	18	18
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	0.053	-10000	0	-0.37	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.07	-10000	0	-0.33	18	18
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.037	-10000	0	-0.81	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.66	16	16
AKT1	0.083	0.089	-9999	-0.6	7	7
PTK2B	0.036	0.13	-9999	-0.53	22	22
VEGFR2 homodimer/Frs2	0.03	0.096	-9999	-1	4	4
CAV1	-0.008	0.13	-9999	-0.81	13	13
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.01	0.1	-9999	-0.86	6	6
endothelial cell proliferation	0.079	0.099	-9999	-0.55	7	7
mol:Ca2+	0.05	0.1	-9999	-0.72	7	7
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.01	0.098	-9999	-0.81	6	6
RP11-342D11.1	0.041	0.1	-9999	-0.73	7	7
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	-0.006	0.061	-9999	-0.58	5	5
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.008	0.064	-9999	-0.81	3	3
HRAS/GDP	-0.009	0.082	-9999	-0.74	5	5
SH2D2A	-0.036	0.18	-9999	-0.61	39	39
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.008	0.069	-9999	-0.69	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.036	0.15	-9999	-0.56	29	29
VEGFR1 homodimer	0.012	0.037	-9999	-0.81	1	1
SHC/GRB2/SOS1	-0.01	0.094	-9999	-0.93	4	4
GRB10	0.05	0.1	-9999	-0.72	7	7
PTPN11	0.012	0.037	-9999	-0.81	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	-0.009	0.094	-9999	-0.78	6	6
HRAS	0.012	0.021	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.077	-9999	-0.48	5	5
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.01	0.095	-9999	-0.79	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.003	0.091	-9999	-0.81	6	6
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.01	0.1	-9999	-0.86	6	6
mol:GDP	-0.009	0.087	-9999	-0.87	4	4
mol:NADP	0.076	0.066	-9999	-0.56	4	4
eNOS/Hsp90	0.079	0.062	-9999	-0.52	4	4
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.05	0.11	-9999	-0.75	7	7
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.064	-9999	-0.81	3	3
VEGFC	0.012	0.037	-9999	-0.81	1	1
FAK1/Vinculin	0.058	0.11	-9999	-0.71	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.13	-9999	-0.57	22	22
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.019	0.063	-9999	-0.58	4	4
mol:L-citrulline	0.076	0.066	-9999	-0.56	4	4
ITGAV	0.01	0.053	-9999	-0.81	2	2
PIK3CA	0.008	0.064	-9999	-0.81	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.01	0.098	-9999	-0.81	6	6
VEGFR2 homodimer/VEGFA homodimer	-0.012	0.12	-9999	-0.84	7	7
VEGFR2/3 heterodimer	0.024	0.13	-9999	-1	7	7
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.051	0.11	-9999	-0.77	7	7
VEGFR2 homodimer	0.029	0.1	-9999	-1.1	4	4
FLT1	0.012	0.037	-9999	-0.81	1	1
NEDD4	0.013	0.053	-9999	-0.81	2	2
MAPK3	0.045	0.1	-9999	-0.64	8	8
MAPK1	0.045	0.1	-9999	-0.64	8	8
VEGFA145/NRP2	-0.02	0.071	-9999	-0.62	3	3
VEGFR1/2 heterodimer	0.029	0.11	-9999	-1.1	4	4
KDR	0.029	0.11	-9999	-1.1	4	4
VEGFA165/NRP1/VEGFR2 homodimer	-0.018	0.11	-9999	-0.78	7	7
SRC	0.013	0.015	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.047	0.11	-9999	-0.66	8	8
PI3K	-0.011	0.094	-9999	-0.75	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.01	0.1	-9999	-0.86	6	6
FES	0.05	0.11	-9999	-0.77	7	7
GAB1	-0.01	0.093	-9999	-0.78	6	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.011	0.1	-9999	-0.86	6	6
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	0.068	0.092	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.01	0.1	-9999	-0.86	6	6
PI3K/GAB1	0.085	0.084	-9999	-0.61	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.009	0.094	-9999	-0.78	6	6
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.014	0.12	-9999	-0.88	8	8
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.05	0.11	-9999	-0.77	7	7
actin cytoskeleton reorganization	-0.036	0.14	-9999	-0.55	29	29
PTK2	0.052	0.12	-9999	-0.79	7	7
EDG1	0.041	0.1	-9999	-0.73	7	7
mol:DAG	0.05	0.11	-9999	-0.75	7	7
CaM/Ca2+	-0.009	0.088	-9999	-0.67	7	7
MAP2K3	0.048	0.12	-9999	-0.98	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.011	0.11	-9999	-0.8	7	7
PLCG1	0.05	0.11	-9999	-0.77	7	7
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.01	0.099	-9999	-0.81	6	6
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.011	0.12	-9999	-0.91	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.01	0.1	-9999	-0.86	6	6
cell migration	0.082	0.096	-9999	-0.64	5	5
mol:PI-3-4-5-P3	-0.01	0.081	-9999	-0.66	6	6
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	0.047	0.095	-9999	-0.68	7	7
mol:NO	0.076	0.066	-9999	-0.56	4	4
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.081	-9999	-0.74	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.049	0.12	-9999	-0.8	7	7
VHL	0.008	0.064	-9999	-0.81	3	3
ITGB3	-0.012	0.14	-9999	-0.81	15	15
NOS3	0.078	0.076	-9999	-0.65	4	4
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.013	0.11	-9999	-0.73	9	9
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.039	0.14	-9999	-0.52	24	24
PRKCB	0.04	0.11	-9999	-0.57	12	12
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.04	0.11	-9999	-0.77	7	7
VEGFR1/2 heterodimer/VEGFA homodimer	-0.011	0.12	-9999	-0.91	6	6
VEGFA165/NRP2	-0.02	0.071	-9999	-0.62	3	3
MAPKKK cascade	-0.009	0.08	-9999	-0.73	5	5
NRP2	-0.013	0.088	-9999	-0.31	40	40
VEGFC homodimer	0.012	0.037	-9999	-0.81	1	1
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.058	0.11	-9999	-0.71	7	7
MAP3K13	0.04	0.14	-9999	-0.6	16	16
PDPK1	0.076	0.09	-9999	-0.71	5	5

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.051	0.1	-9999	-10000	0	0
CRKL	0.037	0.049	-9999	-0.46	2	2
mol:DAG	0.041	0.051	-9999	-0.37	1	1
HRAS	0.061	0.044	-9999	-0.42	1	1
MAPK8	0.018	0.091	-9999	-0.55	11	11
RAP1A	0.037	0.049	-9999	-0.46	2	2
GAB1	0.037	0.049	-9999	-0.46	2	2
MAPK14	0.03	0.03	-9999	-10000	0	0
EPO	0.005	0.038	-9999	-0.3	7	7
PLCG1	0.041	0.052	-9999	-0.38	1	1
EPOR/TRPC2/IP3 Receptors	0.009	0.046	-9999	-0.31	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.021	0.12	-9999	-0.57	23	23
GAB1/SHC/GRB2/SOS1	-0.006	0.029	-9999	-0.45	1	1
EPO/EPOR (dimer)	0.013	0.041	-9999	-0.28	1	1
IRS2	0.037	0.049	-9999	-0.46	2	2
STAT1	0.041	0.078	-9999	-10000	0	0
STAT5B	0.042	0.066	-9999	-0.38	1	1
cell proliferation	0.026	0.086	-9999	-0.51	11	11
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.009	0.036	-9999	-0.44	2	2
TEC	0.037	0.049	-9999	-0.46	2	2
SOCS3	-0.026	0.18	-9999	-0.79	24	24
STAT1 (dimer)	0.041	0.077	-9999	-0.36	1	1
JAK2	0.011	0.053	-9999	-0.82	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.042	0.055	-9999	-0.49	2	2
EPO/EPOR	0.013	0.041	-9999	-0.28	1	1
LYN	0.014	0.004	-9999	-10000	0	0
TEC/VAV2	0.045	0.048	-9999	-0.44	2	2
elevation of cytosolic calcium ion concentration	0.009	0.046	-9999	-0.31	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.028	0.035	-9999	-10000	0	0
mol:IP3	0.041	0.051	-9999	-0.37	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.011	0.036	-9999	-0.47	1	1
SH2B3	0.014	0.005	-9999	-10000	0	0
NFKB1	0.029	0.038	-9999	-0.5	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.017	0.066	-9999	-0.29	25	25
PTPN6	0.03	0.051	-9999	-0.49	2	2
TEC/VAV2/GRB2	0.05	0.046	-9999	-0.48	1	1
EPOR	0.009	0.046	-9999	-0.31	10	10
INPP5D	-0.003	0.071	-9999	-0.31	25	25
mol:GDP	-0.006	0.029	-9999	-0.46	1	1
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
CRKL/CBL/C3G	0.05	0.046	-9999	-0.48	1	1
VAV2	0.037	0.049	-9999	-0.46	2	2
CBL	0.037	0.049	-9999	-0.46	2	2
SHC/Grb2/SOS1	-0.007	0.031	-9999	-0.48	1	1
STAT5A	0.042	0.066	-9999	-0.38	1	1
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.052	0.098	-9999	-0.41	1	1
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.81	1	1
BTK	0.021	0.087	-9999	-0.48	9	9
BCL2	0.002	0.28	-9999	-0.98	36	36

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.059	0.16	-9999	-0.5	58	58
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.15	-9999	-0.41	58	58
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	-0.024	0.065	-9999	-10000	0	0
YY1/LSF	0.028	0.049	-9999	-0.52	4	4
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.012	0.13	-9999	-0.36	57	57
I kappa B alpha/HDAC1	0.001	0.089	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	-0.002	0.11	-9999	-0.32	57	57
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	0.001	0.089	-9999	-10000	0	0
NuRD/MBD3 Complex	0.049	0.02	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.003	0.11	-9999	-0.47	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
GATA1	0.008	0.016	-9999	-0.31	1	1
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	0.064	-9999	-0.81	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	-0.007	0.099	-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	0.027	-9999	-10000	0	0
SIN3 complex	-0.001	0.022	-9999	-0.49	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.037	-9999	-0.81	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.016	0.083	-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	-0.059	0.15	-9999	-0.45	62	62
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	0.089	-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	0.021	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	-0.007	0.099	-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	0.027	0	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.81	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.043	-9999	-0.48	4	4
YY1/SAP30/HDAC1	-0.001	0.021	-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	-0.007	0.099	-9999	-10000	0	0
histone deacetylation	0.049	0.02	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.012	0.083	-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	0.089	-9999	-10000	0	0
GATA1/HDAC1	0	0.009	-9999	-10000	0	0
GATA1/HDAC3	-0.009	0.088	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.075	0.2	-9999	-0.62	57	57
SIN3/HDAC complex/Mad/Max	0.049	0.023	-9999	-10000	0	0
NuRD Complex	0.058	0.021	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.024	0.064	-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	0.038	-9999	-0.49	3	3
GATA1/Fog1	0	0.009	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.087	0.26	-9999	-0.76	64	64
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	-0.051	0.14	-9999	-0.43	57	57
SIN3/HDAC complex/NCoR1	0.046	0.026	-9999	-10000	0	0
TFCP2	0.007	0.074	-9999	-0.81	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

×

Paxillin-dependent events mediated by a4b1

Figure S113. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S113. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.007	-10000	0	-10000	0	0
DOCK1	0.007	0.074	-10000	0	-0.81	4	4
ITGA4	0.002	0.077	-10000	0	-0.44	12	12
RAC1	0.013	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.033	0.12	-10000	0	-0.62	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.046	-10000	0	-0.54	3	3
alpha4/beta7 Integrin/Paxillin	-0.025	0.095	-10000	0	-0.5	17	17
lamellipodium assembly	-0.004	0.057	-10000	0	-0.54	5	5
PIK3CA	0.008	0.064	-10000	0	-0.81	3	3
PI3K	-0.004	0.048	-10000	0	-0.62	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	0.034	-10000	0	-0.42	3	3
cell adhesion	-0.005	0.038	-10000	0	-0.45	3	3
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.005	0.042	-10000	0	-0.49	3	3
ITGB1	0.013	0	-10000	0	-10000	0	0
ITGB7	-0.024	0.15	-10000	0	-0.51	35	35
ARF6/GDP	0.001	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.011	0.068	-10000	0	-0.52	7	7
p130Cas/Crk/Dock1	-0.004	0.048	-10000	0	-0.54	4	4
VCAM1	0.002	0.089	-10000	0	-0.56	10	10
alpha4/beta1 Integrin/Paxillin/Talin	-0.005	0.038	-10000	0	-0.46	3	3
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.038	-10000	0	-0.46	3	3
BCAR1	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.038	0.45	3	-10000	0	3
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	-0.005	0.038	-10000	0	-0.46	3	3
Rac1/GTP	-0.005	0.067	-10000	0	-0.76	3	3

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.011	0.15	-9999	-0.55	33	33
NF kappa B1 p50/RelA/I kappa B alpha	0.043	0.039	-9999	-0.41	1	1
NFKBIA	0.024	0.037	-9999	-0.27	6	6
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.027	0.025	-9999	-0.54	1	1
ARRB2	0.018	0	-9999	-10000	0	0
REL	-0.042	0.21	-9999	-0.81	33	33
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.027	-9999	-0.54	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.025	-9999	-0.54	1	1
PIK3CA	0.008	0.064	-9999	-0.81	3	3
NF kappa B1 p50 dimer	0.02	0.029	-9999	-0.62	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.023	0.029	-9999	-0.62	1	1
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.038	-9999	-10000	0	0
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	-10000	0	0
PI3K	-0.004	0.048	-9999	-0.62	3	3
NF kappa B1 p50/RelA	0.031	0.038	-9999	-10000	0	0
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	0.045	0.036	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.011	0.15	-9999	-0.55	33	33
LCK	-0.01	0.11	-9999	-0.42	27	27
BCL3	0.013	0.015	-9999	-0.31	1	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.009	0.018	-9999	-10000	0	0
BUB1B	0.017	0.027	-9999	-10000	0	0
PLK1	0.017	0.012	-9999	-10000	0	0
PLK1S1	0.015	0.007	-9999	-10000	0	0
KIF2A	0.023	0.029	-9999	-0.58	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	0.001	0.073	-9999	-0.28	16	16
WEE1	0.022	0.011	-9999	-10000	0	0
cytokinesis	0.002	0.072	-9999	-0.31	5	5
PP2A-alpha B56	0.006	0.068	-9999	-0.72	3	3
AURKA	0.016	0.009	-9999	-10000	0	0
PICH/PLK1	0.033	0.018	-9999	-10000	0	0
CENPE	0.019	0.048	-9999	-0.52	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	0.022	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
SPC24	-0.008	0.08	-9999	-0.31	32	32
FBXW11	0.013	0	-9999	-10000	0	0
CLSPN	0.005	0.034	-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	-0.065	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	0.067	-9999	-0.8	3	3
TPT1	0.015	0.007	-9999	-10000	0	0
CDC25C	0.012	0.022	-9999	-10000	0	0
CDC25B	0.012	0.025	-9999	-0.31	3	3
SGOL1	0.009	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	0.004	0.072	-9999	-0.64	6	6
CDC20	0.008	0.041	-9999	-0.31	8	8
PLK1/PBIP1	0.002	0.022	-9999	-10000	0	0
mitosis	0	0.002	-9999	-0.022	3	3
FBXO5	0.021	0.021	-9999	-0.39	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.027	0.11	-9999	-0.31	61	61
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	0.008	0.057	-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	0.038	-9999	-0.47	3	3
mitotic prometaphase	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.035	-9999	-0.3	3	3
microtubule-based process	-0.001	0.06	-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	-0.035	0.12	-9999	-0.31	74	74
APC/C/CDC20	0.02	0.025	-9999	-0.18	1	1
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	0.038	-9999	-0.55	2	2
C13orf34	0.018	0.039	-9999	-0.47	3	3
NUDC	0.015	0.007	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.027	-9999	-10000	0	0
spindle assembly	0.017	0.011	-9999	-10000	0	0
spindle stabilization	0.015	0.007	-9999	-10000	0	0
APC/C/HCDH1	0.012	0.062	-9999	-0.55	6	6
MKLP2/PLK1	-0.001	0.061	-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	-0.003	0.12	-9999	-0.52	25	25
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	0.032	-9999	-0.22	10	10
INCENP	0.009	0.053	-9999	-0.82	2	2

×

HIF-2-alpha transcription factor network

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
MMP14	-0.001	0.025	-10000	0	-10000	0	0
oxygen homeostasis	0.015	0.011	-10000	0	-10000	0	0
TCEB2	0.011	0.025	-10000	0	-0.31	3	3
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.011	0.072	-10000	0	-0.69	4	4
EPO	0.18	0.14	-10000	0	-0.8	2	2
FIH (dimer)	0.028	0.011	-10000	0	-10000	0	0
APEX1	0.027	0.011	-10000	0	-10000	0	0
SERPINE1	0.17	0.17	-10000	0	-0.8	3	3
FLT1	-0.002	0.072	-10000	0	-1.6	1	1
ADORA2A	0.18	0.14	-10000	0	-0.85	2	2
germ cell development	0.19	0.14	-10000	0	-0.84	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	0.028	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.003	0.076	-10000	0	-0.96	2	2
ETS1	0.03	0.003	-10000	0	-10000	0	0
CITED2	-0.093	0.32	-10000	0	-1.2	39	39
KDR	-0.009	0.13	-10000	0	-1.4	4	4
PGK1	0.19	0.15	-10000	0	-0.89	2	2
SIRT1	0.012	0.037	-10000	0	-0.81	1	1
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.2	0.17	-10000	0	-0.96	3	3
EPAS1	0.1	0.1	-10000	0	-0.55	4	4
SP1	0.022	0.002	-10000	0	-10000	0	0
ABCG2	0.18	0.17	-10000	0	-0.88	5	5
EFNA1	0.19	0.15	-10000	0	-0.89	2	2
FXN	0.18	0.14	-10000	0	-0.85	2	2
POU5F1	0.19	0.15	-10000	0	-0.9	2	2
neuron apoptosis	-0.2	0.16	0.91	3	-10000	0	3
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	-0.002	0.14	-10000	0	-0.57	21	21
EGLN2	0.028	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.055	-10000	0	-0.82	2	2
VHL/Elongin B/Elongin C	-0.004	0.047	-10000	0	-0.59	3	3
VHL	0.008	0.064	-10000	0	-0.81	3	3
ARNT	0.027	0.011	-10000	0	-10000	0	0
SLC2A1	0.18	0.14	-10000	0	-0.85	2	2
TWIST1	0.17	0.18	-10000	0	-0.65	10	10
ELK1	0.015	0.026	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.002	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 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
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	0.031	0.008	-9999	-10000	0	0
MAPK12	0.019	0.079	-9999	-0.47	12	12
CCND1	0.017	0.034	-9999	-0.25	1	1
p38 gamma/SNTA1	0.025	0.075	-9999	-0.44	12	12
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.019	0.079	-9999	-0.47	12	12
MAP2K6	0.012	0.085	-9999	-0.52	12	12
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

×

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	-0.73	1	1
PDGFB-D/PDGFRB/SLAP	0.004	0.031	-9999	-0.63	1	1
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.025	-9999	-0.54	1	1
AKT1	0.059	0.043	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.05	-9999	-0.78	1	1
PIK3CA	0.008	0.064	-9999	-0.81	3	3
FGR	0.002	0.028	-9999	-0.56	1	1
mol:Ca2+	0.02	0.048	-9999	-0.82	1	1
MYC	0.02	0.15	-9999	-0.84	13	13
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.028	-9999	-0.45	1	1
LRP1/PDGFRB/PDGFB	-0.002	0.034	-9999	-0.54	2	2
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.81	1	1
GO:0007205	0.02	0.049	-9999	-0.84	1	1
PTEN	0.012	0.037	-9999	-0.81	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.04	0.12	-9999	-0.31	82	82
PDGFB-D/PDGFRB/SHP2	0.003	0.041	-9999	-0.63	2	2
PDGFB-D/PDGFRB/GRB10	0.005	0.03	-9999	-0.63	1	1
cell cycle arrest	-0.001	0.03	-9999	-0.62	1	1
HRAS	0.012	0.021	-9999	-0.31	2	2
HIF1A	0.064	0.039	-9999	-10000	0	0
GAB1	0.013	0.063	-9999	-0.86	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.02	0.059	-9999	-0.78	1	1
PDGFB-D/PDGFRB	0.012	0.031	-9999	-0.56	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.03	-9999	-0.63	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.002	0.047	-9999	-0.74	1	1
positive regulation of MAPKKK cascade	-0.002	0.04	-9999	-0.63	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.02	0.049	-9999	-0.85	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.015	-9999	-0.31	1	1
PDGFB-D/PDGFRB/GRB7	-0.029	0.084	-9999	-0.78	1	1
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.18	0.28	-9999	-0.62	145	145
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.005	0.03	-9999	-0.63	1	1
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.017	0.07	-9999	-0.86	1	1
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.005	0.03	-9999	-0.63	1	1
LCK	-0.008	0.087	-9999	-0.73	6	6
PDGFRB	0.012	0.038	-9999	-0.82	1	1
ACP1	0.013	0	-9999	-10000	0	0
HCK	0.005	0.035	-9999	-0.54	1	1
ABL1	0.009	0.061	-9999	-0.83	1	1
PDGFB-D/PDGFRB/CBL	0.01	0.067	-9999	-0.94	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	0.05	-9999	-0.31	12	12
cell proliferation	0.022	0.13	-9999	-0.73	13	13
SLA	0.013	0.015	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.052	0.024	-9999	-0.42	1	1
SRC	0.006	0.028	-9999	-0.55	1	1
PI3K	-0.004	0.04	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.027	0.065	-9999	-0.69	1	1
SH2B2	0.013	0.015	-9999	-0.31	1	1
PLCgamma1/SPHK1	0.024	0.052	-9999	-0.82	1	1
LYN	0.006	0.029	-9999	-0.55	1	1
LRP1	0.012	0.037	-9999	-0.81	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	-0.44	1	1
SPHK1	0.006	0.05	-9999	-0.31	12	12
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.02	0.049	-9999	-0.85	1	1
PLCG1	0.02	0.051	-9999	-0.89	1	1
NHERF/PDGFRB	-0.002	0.026	-9999	-0.54	1	1
YES1	0.004	0.027	-9999	-0.55	1	1
cell migration	-0.002	0.026	-9999	-0.54	1	1
SHC/Grb2/SOS1	0	0.021	-9999	-0.44	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	0.032	-9999	-0.49	2	2
FYN	0.006	0.028	-9999	-0.55	1	1
DOK1	0.034	0.025	-9999	-0.5	1	1
HRAS/GTP	-0.001	0.013	-9999	-10000	0	0
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.028	0.087	-9999	-0.44	13	13
PRKCD	0.034	0.025	-9999	-0.5	1	1
FER	0.031	0.049	-9999	-0.5	4	4
MAPKKK cascade	-0.001	0.02	-9999	-0.43	1	1
RASA1	0.034	0.025	-9999	-0.5	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	-0.45	1	1
PDGFB-D/PDGFRB/SHB	0.005	0.03	-9999	-0.63	1	1
chemotaxis	0.01	0.059	-9999	-0.79	1	1
STAT1-3-5/STAT1-3-5	-0.003	0.023	-9999	-0.42	1	1
Bovine Papilomavirus E5/PDGFRB	0.001	0.029	-9999	-0.64	1	1
PTPRJ	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.05	0.038	-10000	0	-0.43	3	3
adherens junction organization	0.04	0.038	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.052	0.059	-10000	0	-0.42	7	7
FMN1	0.019	0.11	-10000	0	-0.43	28	28
mol:IP3	-0.002	0.031	-10000	0	-0.4	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	0.035	-10000	0	-0.39	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	0.035	-10000	0	-0.48	2	2
VASP	0.046	0.011	-10000	0	-10000	0	0
ZYX	0.046	0.011	-10000	0	-10000	0	0
JUB	0.045	0.024	-10000	0	-0.43	1	1
EGFR(dimer)	0.041	0.051	-10000	0	-0.45	5	5
E-cadherin/beta catenin-gamma catenin	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.033	-10000	0	-0.42	3	3
PIK3CA	0.009	0.064	-10000	0	-0.81	3	3
PI3K	-0.003	0.033	-10000	0	-0.43	3	3
FYN	0.051	0.034	-10000	0	-0.35	3	3
mol:Ca2+	0.042	0.034	-10000	0	-0.39	3	3
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.002	0.031	-10000	0	-0.4	3	3
CDH1	0.013	0	-10000	0	-10000	0	0
RhoA/GDP	0.052	0.059	-10000	0	-0.42	7	7
establishment of polarity of embryonic epithelium	0.046	0.011	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.005	0.083	-10000	0	-0.81	5	5
CASR	0.042	0.037	-10000	0	-0.38	3	3
RhoA/GTP	-0.002	0.028	-10000	0	-0.36	3	3
AKT2	0.049	0.035	-10000	0	-0.39	3	3
actin cable formation	0.027	0.11	-10000	0	-0.41	28	28
apoptosis	0.002	0.032	0.41	3	-10000	0	3
CTNNA1	0.014	0.001	-10000	0	-10000	0	0
mol:GDP	0.046	0.063	-10000	0	-0.46	7	7
PIP5K1A	0.044	0.036	-10000	0	-0.5	2	2
PLCG1	-0.003	0.032	-10000	0	-0.41	3	3
Rac1/GTP	-0.005	0.042	-10000	0	-0.41	5	5
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.03	-9999	-0.39	3	3
TRAF2/ASK1	-0.001	0.025	-9999	-0.55	1	1
ATM	0.012	0.037	-9999	-0.81	1	1
MAP2K3	0.026	0.057	-9999	-0.52	2	2
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.023	0.079	-9999	-0.42	7	7
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0	0.1	-9999	-0.66	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	-0.013	0.15	-9999	-0.81	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	0.028	-9999	-0.62	1	1
TAK1/TAB family	-0.001	0.014	-9999	-0.21	2	2
RAC1/OSM/MEKK3	-0.001	0.009	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.009	0.033	-9999	-0.38	2	2
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	0.083	-9999	-0.81	5	5
CCM2	0.012	0.021	-9999	-0.31	2	2
CaM/Ca2+/CAMKIIB	-0.006	0.055	-9999	-0.55	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	0.062	-9999	-0.59	5	5
OSM/MEKK3	-0.001	0.013	-9999	-10000	0	0
TAOK1	-0.04	0.16	-9999	-0.46	61	61
TAOK2	0.017	0.021	-9999	-0.44	1	1
TAOK3	0.017	0.021	-9999	-0.44	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	0.037	-9999	-0.81	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.025	-9999	-0.54	1	1
GADD45/MTK1/MTK1	-0.022	0.1	-9999	-0.48	22	22

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	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	-0.04	0.15	-9999	-0.62	32	32
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	-0.04	0.2	-9999	-0.81	32	32
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.012	0.037	-9999	-0.81	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 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
G beta1gamma2/HDAC5	-0.001	0.022	-9999	-0.49	1	1
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0.009	-9999	-10000	0	0
GATA1/HDAC5	0	0.009	-9999	-10000	0	0
GATA2/HDAC5	0	0.009	-9999	-10000	0	0
HDAC5/BCL6/BCoR	-0.001	0.024	-9999	-0.54	1	1
HDAC9	-0.015	0.092	-9999	-0.31	44	44
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	0.028	-9999	-0.62	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	-0.004	0.11	-9999	-0.53	16	16
Tubulin/HDAC6	-0.005	0.054	-9999	-0.54	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	0.008	0.016	-9999	-0.31	1	1
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	-0.006	0.062	-9999	-0.62	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	0.028	-9999	-0.62	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.01	0.067	-9999	-0.54	7	7
HDAC4/ER alpha	-0.042	0.14	-9999	-0.62	23	23
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.036	0.022	-9999	-10000	0	0
cell motility	-0.005	0.054	-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	0.037	-9999	-0.81	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.046	0.19	-9999	-0.52	55	55
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	0.037	-9999	-0.81	1	1
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.001	0.021	-9999	-0.46	1	1
GNG2	0.012	0.037	-9999	-0.81	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.005	0.083	-9999	-0.81	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

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.009	0.035	-9999	-0.31	6	6
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.022	0.024	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.028	0.008	-9999	-10000	0	0
BIRC5	-0.011	0.089	-9999	-0.32	35	35
NFKBIA	0.032	0.009	-9999	-10000	0	0
CPEB1	-0.05	0.22	-9999	-0.81	38	38
AKT1	0.032	0.009	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.012	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.015	-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	0.008	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.012	0.037	-9999	-0.81	1	1
TPX2	0.001	0.068	-9999	-10000	0	0
TP53	0.031	0.007	-9999	-10000	0	0
DLG7	0.021	0.009	-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	0.016	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.011	-9999	-10000	0	0
AURKA	0.026	0.012	-9999	-10000	0	0
AURKB	-0.014	0.028	-9999	-0.14	4	4
CDC25B	0.007	0.019	-9999	-10000	0	0
G2/M transition checkpoint	0.002	0.025	-9999	-0.49	1	1
mRNA polyadenylation	-0.036	0.13	-9999	-0.49	38	38
Aurora A/CPEB	-0.036	0.13	-9999	-0.5	38	38
Aurora A/TACC1/TRAP/chTOG	0.003	0.026	-9999	-0.46	1	1
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.028	0.008	-9999	-10000	0	0
regulation of centrosome cycle	0.002	0.012	-9999	-10000	0	0
spindle assembly	0.002	0.023	-9999	-0.45	1	1
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.007	0.033	-9999	-0.44	1	1
CENPA	-0.01	0.028	-9999	-0.26	4	4
Aurora A/PP2A	0.028	0.008	-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	0.007	-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	0.025	-9999	-0.5	1	1
mitotic prometaphase	0.006	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.012	-9999	-10000	0	0
TACC1	0.012	0.037	-9999	-0.81	1	1
TACC3	0.012	0.021	-9999	-0.31	2	2
Aurora A/Antizyme1	0.003	0.016	-9999	-10000	0	0
Aurora A/RasGAP	0.028	0.008	-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	0.001	0.068	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.019	0.05	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

Arf6 downstream pathway

Figure S125. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S125. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.06	0.12	-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	-0.027	0.039	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.091	0.11	0.51	1	-10000	0	1
ARF1/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GM1	-0.011	0.034	-10000	0	-10000	0	0
mol:Choline	0.012	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.003	0.064	-10000	0	-10000	0	0
MAPK3	-0.017	0.065	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.091	0.11	-10000	0	-0.52	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.023	0.053	-10000	0	-10000	0	0
ARF1/GDP	0.004	0.059	-10000	0	-10000	0	0
ARF6	-0.002	0.023	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.33	114	114
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	-0.006	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	0.01	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	-0.003	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	-0.027	0.039	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GDP	-0.011	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	0.033	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.003	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	0.033	-10000	0	-10000	0	0
PIP5K1A	0.01	0.037	-10000	0	-0.32	2	2
mol:Phosphatidic acid	0.012	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.003	0.064	-10000	0	-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	0.045	0.002	-9999	-10000	0	0
KLHL20	-0.009	0.021	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.073	0.009	-9999	-10000	0	0
ENAH	0.045	0.002	-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	-0.019	0.084	-9999	-0.49	14	14
RAPGEF1	0.057	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	-0.026	0.11	-9999	-0.62	14	14
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	-0.078	0.071	-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	-0.81	1	1
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	-0.001	0.011	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.073	0.009	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.016	-9999	-10000	0	0
CDC42/GDP	0.073	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.027	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.51	35	35
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	0.072	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	11	11
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.045	0.002	-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	-0.018	0.078	-9999	-0.46	14	14
CCND1	0.015	0.039	-9999	-0.18	11	11
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	-0.016	0.074	-9999	-0.43	14	14
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	0.064	-9999	-0.81	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	-0.023	0.16	-10000	0	-0.73	24	24
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	0.067	-10000	0	-0.55	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	0.036	-10000	0	-0.55	2	2
INS	0.009	0.045	-10000	0	-0.56	3	3
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	0.022	-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	0.007	-10000	0	-10000	0	0
ACAP1	0.026	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	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	0.01	0.071	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.017	0.08	-10000	0	-0.4	20	20
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	0.009	-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	0.022	0.49	1	-10000	0	1
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.029	0.073	-10000	0	-0.43	12	12
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.012	0.037	-10000	0	-0.81	1	1
Dynamin 2/GDP	0.026	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.031	0.067	-10000	0	-0.43	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	0.03	-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	0.003	-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	0.001	0.062	-9999	-0.31	19	19
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	0.027	-9999	-0.42	2	2
ARF1/GTP	-0.001	0.016	-9999	-0.25	2	2
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	0.027	-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	0.018	0	-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	0.009	-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	0.035	0.016	-9999	-10000	0	0
PLD2	-0.002	0.027	-9999	-0.42	2	2
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	-0.002	0.027	-9999	-0.43	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.001	0.015	-9999	-0.23	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	-10000	0	0
USO1	-0.001	0.011	-9999	-10000	0	0
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	-0.006	0.03	-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	0.037	-9999	-0.81	1	1
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.028	-9999	-0.62	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	-0.81	-0.81	-0.81	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	-0.49	-0.49	-0.49	-0.49
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.016
84_STAT5B	0.047	-0.096	0	-0.097
84_STAT5A	0.047	-0.096	0	-0.097