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

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	256
Signaling events mediated by Stem cell factor receptor (c-Kit)	168
Signaling events regulated by Ret tyrosine kinase	149
TCGA08_retinoblastoma	140
Reelin signaling pathway	131
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	121
IL4-mediated signaling events	112
Wnt signaling	108
PDGFR-alpha signaling pathway	99
FOXA2 and FOXA3 transcription factor networks	96

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	0.5110	256	1795	7	-0.52	0	1000	-1000	-0.029	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3353	168	13171	78	-0.81	0.24	1000	-1000	-0.08	-1000
Signaling events regulated by Ret tyrosine kinase	0.2974	149	12277	82	-0.46	0.013	1000	-1000	-0.083	-1000
TCGA08_retinoblastoma	0.2794	140	1126	8	-0.12	0.072	1000	-1000	-0.015	-1000
Reelin signaling pathway	0.2615	131	7350	56	-0.59	0.033	1000	-1000	-0.078	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2415	121	8257	68	-0.9	0.37	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.2236	112	10233	91	-1.3	0.67	1000	-1000	-0.12	-1000
Wnt signaling	0.2156	108	760	7	-0.41	0.013	1000	-1000	-0.028	-1000
PDGFR-alpha signaling pathway	0.1976	99	4366	44	-0.48	0.033	1000	-1000	-0.055	-1000
FOXA2 and FOXA3 transcription factor networks	0.1916	96	4416	46	-0.91	0.021	1000	-1000	-0.05	-1000
Noncanonical Wnt signaling pathway	0.1876	94	2447	26	-0.41	0.013	1000	-1000	-0.088	-1000
Nongenotropic Androgen signaling	0.1756	88	4595	52	-0.34	0.16	1000	-1000	-0.056	-1000
Signaling events mediated by the Hedgehog family	0.1637	82	4278	52	-0.38	0.2	1000	-1000	-0.079	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1597	80	4363	54	-0.59	0.028	1000	-1000	-0.088	-1000
Calcium signaling in the CD4+ TCR pathway	0.1557	78	2438	31	-0.52	0.013	1000	-1000	-0.083	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1497	75	2561	34	-0.17	0.013	1000	-1000	-0.057	-1000
Endothelins	0.1337	67	6455	96	-0.39	0.013	1000	-1000	-0.066	-1000
Glypican 1 network	0.1317	66	3189	48	-0.38	0.028	1000	-1000	-0.043	-1000
IGF1 pathway	0.1277	64	3660	57	-0.19	0.058	1000	-1000	-0.094	-1000
Ephrin B reverse signaling	0.1257	63	3057	48	-0.3	0.18	1000	-1000	-0.073	-1000
HIF-1-alpha transcription factor network	0.1218	61	4707	76	-0.57	0.041	1000	-1000	-0.098	-1000
IL23-mediated signaling events	0.1118	56	3411	60	-0.31	0.019	1000	-1000	-0.14	-1000
BMP receptor signaling	0.1058	53	4323	81	-0.57	0.026	1000	-1000	-0.095	-1000
Glucocorticoid receptor regulatory network	0.1058	53	6101	114	-0.56	0.36	1000	-1000	-0.075	-1000
TCR signaling in naïve CD8+ T cells	0.1058	53	5001	93	-0.2	0.088	1000	-1000	-0.086	-1000
Glypican 2 network	0.1058	53	212	4	-0.087	-0.009	1000	-1000	-0.037	-1000
Arf6 signaling events	0.1038	52	3282	62	-0.32	0.02	1000	-1000	-0.069	-1000
Coregulation of Androgen receptor activity	0.0998	50	3807	76	-0.78	0.062	1000	-1000	-0.043	-1000
Syndecan-1-mediated signaling events	0.0998	50	1728	34	-0.2	0.013	1000	-1000	-0.05	-1000
EPHB forward signaling	0.0958	48	4123	85	-0.3	0.15	1000	-1000	-0.09	-1000
Syndecan-4-mediated signaling events	0.0818	41	2793	67	-0.26	0.023	1000	-1000	-0.086	-1000
IL12-mediated signaling events	0.0798	40	3543	87	-0.4	0.026	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	0.0778	39	2554	65	-0.66	0.061	1000	-1000	-0.061	-1000
amb2 Integrin signaling	0.0758	38	3162	82	-0.24	0.013	1000	-1000	-0.076	-1000
IL6-mediated signaling events	0.0758	38	2883	75	-0.2	0.06	1000	-1000	-0.081	-1000
Signaling mediated by p38-alpha and p38-beta	0.0739	37	1645	44	-0.23	0.013	1000	-1000	-0.052	-1000
EGFR-dependent Endothelin signaling events	0.0679	34	727	21	-0.11	0.013	1000	-1000	-0.067	-1000
Thromboxane A2 receptor signaling	0.0659	33	3507	105	-0.22	0.034	1000	-1000	-0.063	-1000
Osteopontin-mediated events	0.0639	32	1219	38	-0.26	0.013	1000	-1000	-0.09	-1000
Ras signaling in the CD4+ TCR pathway	0.0639	32	560	17	-0.088	0.013	1000	-1000	-0.04	-1000
BCR signaling pathway	0.0619	31	3132	99	-0.2	0.023	1000	-1000	-0.077	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0599	30	2618	85	-0.27	0.013	1000	-1000	-0.067	-1000
FAS signaling pathway (CD95)	0.0599	30	1444	47	-0.23	0.031	1000	-1000	-0.046	-1000
TCGA08_p53	0.0579	29	207	7	-0.081	0.052	1000	-1000	-0.009	-1000
IL27-mediated signaling events	0.0579	29	1495	51	-0.15	0.067	1000	-1000	-0.074	-1000
Plasma membrane estrogen receptor signaling	0.0579	29	2529	86	-0.18	0.021	1000	-1000	-0.074	-1000
Syndecan-2-mediated signaling events	0.0539	27	1915	69	-0.22	0.038	1000	-1000	-0.059	-1000
Regulation of p38-alpha and p38-beta	0.0539	27	1491	54	-0.47	0.013	1000	-1000	-0.06	-1000
Regulation of Androgen receptor activity	0.0539	27	1928	70	-0.48	0.034	1000	-1000	-0.055	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0519	26	1363	52	-0.28	0.054	1000	-1000	-0.059	-1000
Visual signal transduction: Rods	0.0519	26	1396	52	-0.2	0.013	1000	-1000	-0.087	-1000
Integrins in angiogenesis	0.0499	25	2132	84	-0.23	0.034	1000	-1000	-0.085	-1000
ErbB2/ErbB3 signaling events	0.0479	24	1589	65	-0.12	0.027	1000	-1000	-0.061	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0459	23	2066	88	-0.32	0.03	1000	-1000	-0.095	-1000
Signaling events mediated by PRL	0.0459	23	794	34	-0.11	0.013	1000	-1000	-0.04	-1000
JNK signaling in the CD4+ TCR pathway	0.0439	22	389	17	-0.1	0.019	1000	-1000	-0.077	-1000
Signaling events mediated by PTP1B	0.0439	22	1686	76	-0.25	0.021	1000	-1000	-0.078	-1000
LPA receptor mediated events	0.0439	22	2340	102	-0.25	0.031	1000	-1000	-0.087	-1000
VEGFR1 specific signals	0.0419	21	1214	56	-0.071	0.041	1000	-1000	-0.068	-1000
Regulation of nuclear SMAD2/3 signaling	0.0399	20	2757	136	-0.34	0.064	1000	-1000	-0.07	-1000
Aurora C signaling	0.0399	20	140	7	-0.061	0	1000	-1000	-0.043	-1000
Nectin adhesion pathway	0.0399	20	1319	63	-0.26	0.03	1000	-1000	-0.078	-1000
Visual signal transduction: Cones	0.0379	19	726	38	-0.088	0.013	1000	-1000	-0.061	-1000
p75(NTR)-mediated signaling	0.0379	19	2443	125	-0.36	0.067	1000	-1000	-0.097	-1000
Fc-epsilon receptor I signaling in mast cells	0.0379	19	1856	97	-0.2	0.03	1000	-1000	-0.087	-1000
IL1-mediated signaling events	0.0359	18	1143	62	-0.12	0.066	1000	-1000	-0.1	-1000
Syndecan-3-mediated signaling events	0.0359	18	655	35	-0.16	0.013	1000	-1000	-0.055	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0359	18	2236	120	-0.31	0.042	1000	-1000	-0.074	-1000
FOXM1 transcription factor network	0.0359	18	947	51	-0.17	0.053	1000	-1000	-0.15	-1000
ErbB4 signaling events	0.0339	17	1213	69	-0.14	0.058	1000	-1000	-0.079	-1000
TCGA08_rtk_signaling	0.0339	17	461	26	-0.24	0.025	1000	-1000	-0.017	-1000
Rapid glucocorticoid signaling	0.0339	17	342	20	-0.094	0.015	1000	-1000	-0.036	-1000
LPA4-mediated signaling events	0.0299	15	189	12	-0.12	0.015	1000	-1000	-0.018	-1000
Presenilin action in Notch and Wnt signaling	0.0299	15	949	61	-0.2	0.042	1000	-1000	-0.072	-1000
Effects of Botulinum toxin	0.0299	15	393	26	-0.16	0.019	1000	-1000	-0.064	-1000
IL2 signaling events mediated by STAT5	0.0299	15	346	22	-0.067	0.039	1000	-1000	-0.046	-1000
Insulin Pathway	0.0299	15	1158	74	-0.084	0.035	1000	-1000	-0.092	-1000
Signaling events mediated by HDAC Class III	0.0279	14	564	40	-0.36	0.024	1000	-1000	-0.049	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0279	14	471	33	-0.16	0.035	1000	-1000	-0.065	-1000
Class IB PI3K non-lipid kinase events	0.0279	14	42	3	-0.003	-1000	1000	-1000	-0.01	-1000
Aurora B signaling	0.0279	14	971	67	-0.38	0.014	1000	-1000	-0.072	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0259	13	367	28	-0.18	0.031	1000	-1000	-0.054	-1000
a4b1 and a4b7 Integrin signaling	0.0259	13	68	5	-0.033	0.003	1000	-1000	-0.034	-1000
Ceramide signaling pathway	0.0259	13	1038	76	-0.18	0.024	1000	-1000	-0.051	-1000
IL2 signaling events mediated by PI3K	0.0259	13	803	58	-0.066	0.031	1000	-1000	-0.083	-1000
mTOR signaling pathway	0.0240	12	650	53	-0.046	0.021	1000	-1000	-0.058	-1000
IFN-gamma pathway	0.0240	12	819	68	-0.11	0.041	1000	-1000	-0.09	-1000
BARD1 signaling events	0.0220	11	631	57	-0.035	0.052	1000	-1000	-0.063	-1000
Cellular roles of Anthrax toxin	0.0220	11	432	39	-0.088	0.019	1000	-1000	-0.03	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0220	11	527	45	-0.088	0.039	1000	-1000	-0.087	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0220	11	825	74	-0.18	0.085	1000	-1000	-0.093	-1000
Class I PI3K signaling events	0.0220	11	823	73	-0.25	0.032	1000	-1000	-0.065	-1000
Regulation of Telomerase	0.0220	11	1159	102	-0.28	0.052	1000	-1000	-0.1	-1000
Caspase cascade in apoptosis	0.0180	9	726	74	-0.088	0.028	1000	-1000	-0.054	-1000
Retinoic acid receptors-mediated signaling	0.0180	9	522	58	-0.11	0.034	1000	-1000	-0.075	-1000
S1P3 pathway	0.0180	9	399	42	-0.18	0.049	1000	-1000	-0.057	-1000
TRAIL signaling pathway	0.0160	8	395	48	-0.075	0.047	1000	-1000	-0.069	-1000
ceramide signaling pathway	0.0160	8	429	49	-0.088	0.031	1000	-1000	-0.042	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0160	8	700	83	-0.21	0.052	1000	-1000	-0.076	-1000
Circadian rhythm pathway	0.0140	7	164	22	-0.057	0.013	1000	-1000	-0.054	-1000
Signaling events mediated by HDAC Class I	0.0140	7	735	104	-0.088	0.059	1000	-1000	-0.061	-1000
Canonical Wnt signaling pathway	0.0140	7	379	51	-0.048	0.067	1000	-1000	-0.063	-1000
Arf6 downstream pathway	0.0120	6	290	43	-0.17	0.093	1000	-1000	-0.038	-1000
Insulin-mediated glucose transport	0.0120	6	204	32	-0.21	0.042	1000	-1000	-0.063	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0120	6	239	37	-0.035	0.04	1000	-1000	-0.06	-1000
S1P1 pathway	0.0120	6	246	36	-0.028	0.033	1000	-1000	-0.057	-1000
Canonical NF-kappaB pathway	0.0100	5	226	39	-0.088	0.073	1000	-1000	-0.081	-1000
Atypical NF-kappaB pathway	0.0100	5	160	31	-0.041	0.047	1000	-1000	-0.041	-1000
EPO signaling pathway	0.0080	4	245	55	-0.025	0.061	1000	-1000	-0.083	-1000
Paxillin-dependent events mediated by a4b1	0.0080	4	147	36	-0.033	0.024	1000	-1000	-0.072	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0080	4	595	125	-0.036	0.086	1000	-1000	-0.089	-1000
E-cadherin signaling in the nascent adherens junction	0.0080	4	377	76	-0.17	0.074	1000	-1000	-0.079	-1000
PLK1 signaling events	0.0060	3	284	85	-0.035	0.033	1000	-1000	-0.057	-1000
Class I PI3K signaling events mediated by Akt	0.0060	3	267	68	-0.21	0.052	1000	-1000	-0.06	-1000
S1P5 pathway	0.0060	3	67	17	-0.016	0.022	1000	-1000	-0.058	-1000
HIF-2-alpha transcription factor network	0.0060	3	147	43	-0.2	0.2	1000	-1000	-0.074	-1000
Signaling mediated by p38-gamma and p38-delta	0.0060	3	53	15	0	0.031	1000	-1000	-0.027	-1000
PDGFR-beta signaling pathway	0.0060	3	368	97	-0.18	0.064	1000	-1000	-0.083	-1000
S1P4 pathway	0.0060	3	77	25	-0.016	0.032	1000	-1000	-0.055	-1000
p38 MAPK signaling pathway	0.0060	3	154	44	-0.041	0.025	1000	-1000	-0.07	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0040	2	67	23	-0.04	0.049	1000	-1000	-0.073	-1000
Signaling events mediated by HDAC Class II	0.0040	2	180	75	-0.046	0.035	1000	-1000	-0.06	-1000
PLK2 and PLK4 events	0.0040	2	6	3	0.009	0.022	1000	-1000	-0.015	-1000
Aurora A signaling	0.0040	2	167	60	-0.051	0.038	1000	-1000	-0.059	-1000
E-cadherin signaling in keratinocytes	0.0040	2	128	43	-0.004	0.052	1000	-1000	-0.064	-1000
FoxO family signaling	0.0020	1	123	64	-0.21	0.16	1000	-1000	-0.061	-1000
Arf6 trafficking events	0.0020	1	83	71	-0.022	0.046	1000	-1000	-0.084	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.056	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.041	-1000
Arf1 pathway	0.0000	0	37	54	-0.006	0.035	1000	-1000	-0.047	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.056	-1000
Total	NA	4194	230661	7203	-29	-990	131000	-131000	-8.7	-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	350	350
EFNA5	-0.11	0.3	-9999	-0.81	76	76
FYN	-0.38	0.3	-9999	-0.56	350	350
neuron projection morphogenesis	-0.42	0.31	-9999	-0.61	350	350
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.43	0.31	-9999	-0.61	350	350
EPHA5	-0.52	0.4	-9999	-0.82	319	319

×

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	295	295
CRKL	-0.22	0.24	-10000	0	-0.42	288	288
HRAS	-0.19	0.21	-10000	0	-0.5	47	47
mol:PIP3	-0.22	0.22	-10000	0	-0.41	288	288
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.012	0.037	-10000	0	-0.82	1	1
GAB1	-0.24	0.25	-10000	0	-0.45	288	288
FOXO3	-0.2	0.22	-10000	0	-0.38	288	288
AKT1	-0.22	0.23	-10000	0	-0.42	288	288
BAD	-0.2	0.22	-10000	0	-0.38	288	288
megakaryocyte differentiation	-0.25	0.24	-10000	0	-0.45	296	296
GSK3B	-0.2	0.22	-10000	0	-0.38	288	288
RAF1	-0.15	0.18	-10000	0	-0.46	25	25
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.24	0.25	-10000	0	-0.45	288	288
STAT1	-0.6	0.58	-10000	0	-1.1	290	290
HRAS/SPRED1	-0.18	0.14	-10000	0	-0.44	28	28
cell proliferation	-0.24	0.26	-10000	0	-0.45	291	291
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	288	288
HRAS/SPRED2	-0.18	0.14	-10000	0	-0.44	29	29
LYN/TEC/p62DOK	-0.24	0.21	-10000	0	-0.41	288	288
MAPK3	-0.098	0.13	-10000	0	-0.31	22	22
STAP1	-0.27	0.25	-10000	0	-0.48	288	288
GRAP2	-0.045	0.21	-10000	0	-0.82	33	33
JAK2	-0.52	0.45	-10000	0	-0.9	290	290
STAT1 (dimer)	-0.59	0.57	-10000	0	-1.1	290	290
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.25	0.21	-10000	0	-0.42	289	289
actin filament polymerization	-0.24	0.24	-10000	0	-0.44	289	289
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.36	0.34	-10000	0	-0.64	288	288
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.22	0.19	-10000	0	-0.37	286	286
PI3K	-0.22	0.24	-10000	0	-0.42	289	289
PTEN	0.012	0.037	-10000	0	-0.82	1	1
SCF/KIT/EPO/EPOR	-0.75	0.71	-10000	0	-1.4	288	288
MAPK8	-0.25	0.26	-10000	0	-0.46	291	291
STAT3 (dimer)	-0.24	0.24	-10000	0	-0.44	288	288
positive regulation of transcription	-0.078	0.11	-10000	0	-0.25	22	22
mol:GDP	-0.23	0.19	-10000	0	-0.55	47	47
PIK3C2B	-0.24	0.25	-10000	0	-0.45	288	288
CBL/CRKL	-0.2	0.22	-10000	0	-0.39	288	288
FER	-0.24	0.25	-10000	0	-0.45	289	289
SH2B3	-0.24	0.25	-10000	0	-0.45	288	288
PDPK1	-0.2	0.21	-10000	0	-0.37	289	289
SNAI2	-0.25	0.26	-10000	0	-0.46	290	290
positive regulation of cell proliferation	-0.42	0.42	-10000	0	-0.77	290	290
KITLG	-0.005	0.11	-10000	0	-0.85	8	8
cell motility	-0.42	0.42	-10000	0	-0.77	290	290
PTPN6	0.021	0.017	-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	290	290
SOCS1	0.008	0.049	-10000	0	-0.4	6	6
cell migration	0.24	0.25	0.45	291	-10000	0	291
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.005	0.041	-10000	0	-0.33	7	7
VAV1	-0.015	0.1	-10000	0	-0.35	39	39
GRB10	-0.24	0.25	-10000	0	-0.45	288	288
PTPN11	0.02	0.038	-10000	0	-0.8	1	1
SCF/KIT	-0.26	0.26	-10000	0	-0.48	288	288
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.11	0.14	-10000	0	-0.35	22	22
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.81	0.75	-10000	0	-1.4	288	288
MAP2K2	-0.11	0.14	-10000	0	-0.35	22	22
SHC/Grb2/SOS1	-0.24	0.21	-10000	0	-0.41	288	288
STAT5A	-0.35	0.36	-10000	0	-0.65	290	290
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.24	0.25	-10000	0	-0.45	290	290
SHC/GRAP2	-0.043	0.16	-10000	0	-0.63	33	33
PTPRO	-0.26	0.25	-10000	0	-0.46	296	296
SH2B2	-0.24	0.25	-10000	0	-0.45	289	289
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.25	0.25	-10000	0	-0.46	291	291
CREBBP	0.017	0.02	-10000	0	-10000	0	0
BCL2	-0.22	0.42	-10000	0	-1.6	38	38

×

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	0.069	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.25	0.2	-9999	-0.5	123	123
JUN	-0.32	0.31	-9999	-0.66	183	183
HRAS	0.012	0.021	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.38	0.32	-9999	-0.6	308	308
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	308	308
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.82	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.29	0.25	-9999	-0.51	283	283
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.34	0.29	-9999	-0.55	308	308
GRB7	-0.041	0.12	-9999	-0.31	84	84
RET51/GFRalpha1/GDNF	-0.38	0.32	-9999	-0.6	308	308
MAPKKK cascade	-0.3	0.26	-9999	-0.49	308	308
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.34	0.31	-9999	-0.58	296	296
lamellipodium assembly	-0.24	0.18	-9999	-0.38	284	284
RET51/GFRalpha1/GDNF/SHC	-0.38	0.32	-9999	-0.6	308	308
PIK3CA	0.008	0.064	-9999	-0.82	3	3
RET9/GFRalpha1/GDNF/SHC	-0.29	0.25	-9999	-0.51	283	283
RET9/GFRalpha1/GDNF/Shank3	-0.29	0.25	-9999	-0.51	283	283
MAPK3	-0.31	0.29	-9999	-0.51	308	308
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.12	0.3	-9999	-0.82	79	79
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.3	0.29	-9999	-0.5	308	308
DOK5	-0.099	0.28	-9999	-0.82	68	68
GFRA1	-0.46	0.41	-9999	-0.82	284	284
MAPK8	-0.23	0.24	-9999	-0.59	95	95
HRAS/GTP	-0.35	0.3	-9999	-0.56	308	308
tube development	-0.27	0.23	-9999	-0.47	283	283
MAPK1	-0.31	0.29	-9999	-0.51	308	308
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.18	0.18	-9999	-0.34	283	283
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
PDLIM7	0.011	0.029	-9999	-0.31	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.43	0.38	-9999	-0.66	319	319
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.38	0.32	-9999	-0.61	308	308
RET51/GFRalpha1/GDNF/Dok5	-0.45	0.38	-9999	-0.68	320	320
PRKCA	-0.018	0.16	-9999	-0.82	19	19
HRAS/GDP	-0.001	0.013	-9999	-0.21	2	2
CREB1	-0.24	0.24	-9999	-0.43	283	283
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.18	0.18	-9999	-0.34	283	283
RET51/GFRalpha1/GDNF/Grb7	-0.41	0.33	-9999	-0.63	308	308
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.17	0.32	-9999	-0.63	139	139
DOK4	0.013	0.015	-9999	-0.31	1	1
JNK cascade	-0.31	0.3	-9999	-0.64	183	183
RET9/GFRalpha1/GDNF/FRS2	-0.29	0.25	-9999	-0.51	283	283
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	283	283
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.25	0.24	-9999	-0.55	111	111
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.24	0.23	-9999	-0.41	308	308
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.28	0.31	-9999	-0.47	308	308
PI3K	-0.36	0.34	-9999	-0.62	284	284
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.27	0.23	-9999	-0.47	283	283
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.22	0.21	-9999	-0.52	87	87
RET51/GFRalpha1/GDNF/FRS2	-0.38	0.32	-9999	-0.6	308	308
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.084	0.27	-9999	-0.82	59	59
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.28	0.31	-9999	-0.47	308	308
RET51/GFRalpha1/GDNF/PKC alpha	-0.4	0.35	-9999	-0.63	309	309
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	0.37	-9999	-0.67	320	320
Rac1/GTP	-0.29	0.23	-9999	-0.46	284	284
RET9/GFRalpha1/GDNF	-0.32	0.27	-9999	-0.56	283	283
GFRalpha1/GDNF	-0.36	0.31	-9999	-0.63	283	283

×

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	208	208
CDKN2C	0.026	0.036	-10000	0	-0.32	3	3
CDKN2A	-0.12	0.16	-10000	0	-0.32	207	207
CCND2	0.069	0.072	0.17	141	-10000	0	141
RB1	-0.068	0.072	-10000	0	-0.17	141	141
CDK4	0.069	0.071	0.17	142	-10000	0	142
CDK6	0.072	0.077	0.18	141	-0.18	2	143
G1/S progression	0.06	0.079	0.17	141	-10000	0	141

×

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	0.016	-9999	-10000	0	0
VLDLR	-0.021	0.17	-9999	-0.82	21	21
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.01	0.033	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.42	0.26	-9999	-0.56	372	372
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.067	-9999	-0.46	11	11
AKT1	-0.24	0.17	-9999	-0.34	193	193
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
RELN/LRP8/DAB1	-0.39	0.25	-9999	-0.52	370	370
LRPAP1/LRP8	-0.026	0.12	-9999	-0.63	21	21
RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	370	370
DAB1/alpha3/beta1 Integrin	-0.34	0.23	-9999	-0.46	376	376
long-term memory	-0.36	0.24	-9999	-0.49	372	372
DAB1/LIS1	-0.35	0.23	-9999	-0.47	376	376
DAB1/CRLK/C3G	-0.34	0.23	-9999	-0.49	203	203
PIK3CA	0.008	0.064	-9999	-0.82	3	3
DAB1/NCK2	-0.36	0.24	-9999	-0.48	376	376
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.021	0.16	-9999	-0.63	27	27
CDK5R1	0.011	0.025	-9999	-0.31	3	3
RELN	-0.59	0.37	-9999	-0.82	366	366
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.42	0.26	-9999	-0.56	370	370
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.38	0.25	-9999	-0.5	372	372
MAPK8	-0.005	0.12	-9999	-0.82	11	11
RELN/VLDLR/DAB1	-0.39	0.24	-9999	-0.52	372	372
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.36	0.26	-9999	-0.5	376	376
RELN/LRP8	-0.42	0.26	-9999	-0.56	370	370
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	370	370
PI3K	-0.004	0.048	-9999	-0.63	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.02	-9999	-10000	0	0
RAP1A	-0.3	0.23	-9999	-0.82	29	29
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.003	0.015	-9999	-0.31	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.14	-9999	-0.53	23	23
neuron adhesion	-0.28	0.22	-9999	-0.73	33	33
LRP8	-0.021	0.17	-9999	-0.82	21	21
GSK3B	-0.22	0.16	-9999	-0.62	17	17
RELN/VLDLR/DAB1/Fyn	-0.36	0.23	-9999	-0.49	372	372
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.36	373	373
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.033	0.087	-9999	-0.56	5	5
neuron migration	-0.3	0.22	-9999	-0.42	367	367
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.14	-9999	-0.53	23	23
RELN/VLDLR	-0.4	0.26	-9999	-0.53	376	376

×

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	-0.041	0.16	-10000	0	-0.51	38	38
NFATC2	-0.24	0.38	-10000	0	-0.81	131	131
NFATC3	-0.084	0.13	-10000	0	-0.31	25	25
CD40LG	-0.74	0.57	-10000	0	-1.2	276	276
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	161	161
JUNB	0.003	0.09	-10000	0	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.015	-10000	0	-0.34	1	1
T cell anergy	0.025	0.065	-10000	0	-0.49	1	1
TLE4	-0.24	0.44	-10000	0	-0.86	143	143
Jun/NFAT1-c-4/p21SNFT	-0.66	0.6	-10000	0	-1.2	252	252
AP-1/NFAT1-c-4	-0.9	0.78	-10000	0	-1.5	278	278
IKZF1	-0.18	0.34	-10000	0	-0.76	95	95
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.81	134	134
AP-1/NFAT1	-0.42	0.48	-10000	0	-0.89	220	220
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.84	-10000	0	-1.6	238	238
EGR3	-0.56	0.72	-10000	0	-1.6	126	126
NFAT1/FOXP3	-0.22	0.34	-10000	0	-0.69	134	134
EGR1	-0.17	0.34	-10000	0	-0.82	108	108
JUN	-0.18	0.34	-10000	0	-0.82	113	113
EGR4	-0.036	0.18	-10000	0	-0.72	31	31
mol:Ca2+	0.016	0.01	-10000	0	-10000	0	0
GBP3	-0.16	0.32	-10000	0	-0.7	105	105
FOSL1	-0.033	0.12	-10000	0	-0.32	69	69
NFAT1-c-4/MAF/IRF4	-0.56	0.56	-10000	0	-1	251	251
DGKA	-0.16	0.3	-10000	0	-0.66	105	105
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.55	0.56	-10000	0	-1	250	250
CTLA4	-0.24	0.39	-10000	0	-0.81	126	126
NFAT1-c-4 (dimer)/EGR1	-0.64	0.66	-10000	0	-1.2	247	247
NFAT1-c-4 (dimer)/EGR4	-0.58	0.56	-10000	0	-1.1	249	249
FOS	-0.21	0.36	-10000	0	-0.82	128	128
IFNG	-0.43	0.54	-10000	0	-1.1	154	154
T cell activation	-0.44	0.42	-10000	0	-0.95	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	0.8	181	-10000	0	181
TNF	-0.6	0.57	-10000	0	-1.1	252	252
FASLG	-0.75	0.78	-10000	0	-1.4	253	253
TBX21	-0.039	0.18	-10000	0	-0.67	34	34
BATF3	-0.006	0.082	-10000	0	-0.33	28	28
PRKCQ	0.003	0.091	-10000	0	-0.82	6	6
PTPN1	-0.16	0.3	-10000	0	-0.67	101	101
NFAT1-c-4/ICER1	-0.55	0.55	-10000	0	-1	249	249
GATA3	-0.03	0.18	-10000	0	-0.78	28	28
T-helper 1 cell differentiation	-0.41	0.52	-10000	0	-1.1	154	154
IL2RA	-0.49	0.46	-10000	0	-1	162	162
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.3	-10000	0	-0.66	106	106
E2F1	-0.08	0.15	-10000	0	-0.3	154	154
PPARG	-0.001	0.1	-10000	0	-0.61	12	12
SLC3A2	-0.16	0.3	-10000	0	-0.67	101	101
IRF4	-0.1	0.24	-10000	0	-0.47	117	117
PTGS2	-0.71	0.56	-10000	0	-1.2	263	263
CSF2	-0.78	0.53	-10000	0	-1.2	279	279
JunB/Fra1/NFAT1-c-4	-0.54	0.53	-10000	0	-1	245	245
IL4	-0.33	0.37	-10000	0	-0.87	131	131
IL5	-0.7	0.54	-10000	0	-1.1	268	268
IL2	-0.45	0.44	-10000	0	-0.98	172	172
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	-0.81	178	178
CDK4	0.22	0.24	0.6	65	-10000	0	65
PTPRK	-0.16	0.3	-10000	0	-0.7	86	86
IL8	-0.72	0.54	-10000	0	-1.2	263	263
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.6	0.44	-10000	0	-1.1	183	183
STAT6 (cleaved dimer)	-0.66	0.44	-10000	0	-1	271	271
IGHG1	-0.21	0.14	-10000	0	-0.34	111	111
IGHG3	-0.59	0.42	-10000	0	-0.94	254	254
AKT1	-0.32	0.26	-10000	0	-0.67	99	99
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.25	-10000	0	-0.7	69	69
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.68	145	145
THY1	-0.6	0.44	-10000	0	-1.1	176	176
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	-0.68	216	216
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.65	108	108
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	-0.98	265	265
SOCS1	-0.41	0.29	-10000	0	-0.72	143	143
SOCS3	-0.37	0.34	-10000	0	-0.98	72	72
FCER2	-0.63	0.47	-10000	0	-0.97	275	275
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.67	0.47	-10000	0	-1.1	230	230
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.63	62	62
T cell proliferation	-0.61	0.46	-10000	0	-1	216	216
IL4R/JAK1	-0.6	0.44	-10000	0	-1	211	211
EGR2	-0.96	0.72	-10000	0	-1.6	268	268
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	-0.58	34	34
CCL26	-0.62	0.45	-10000	0	-1.1	197	197
IL4R	-0.64	0.46	-10000	0	-1.1	222	222
PTPN6	0.029	0.009	-10000	0	-10000	0	0
IL13RA2	-0.71	0.56	-10000	0	-1.2	243	243
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.35	0.5	-10000	0	-1	131	131
ARG1	-0.15	0.12	-10000	0	-10000	0	0
CBL	-0.39	0.29	-10000	0	-0.66	199	199
GTF3A	0.017	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
IL13RA1/JAK2	-0.026	0.052	-10000	0	-0.66	2	2
IRF4/BCL6	-0.32	0.45	-10000	0	-1.1	102	102
CD40LG	-0.13	0.31	-10000	0	-0.8	88	88
MAPK14	-0.39	0.31	-10000	0	-0.72	161	161
mitosis	-0.31	0.24	-10000	0	-0.63	101	101
STAT6	-0.68	0.51	-10000	0	-1.1	248	248
SPI1	0	0.074	-10000	0	-0.31	27	27
RPS6KB1	-0.29	0.23	-10000	0	-0.63	83	83
STAT6 (dimer)	-0.68	0.51	-10000	0	-1.1	248	248
STAT6 (dimer)/PARP14	-0.64	0.47	-10000	0	-1	249	249
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	-0.69	100	100
FRAP1	-0.32	0.26	-10000	0	-0.67	100	100
LTA	-0.62	0.45	-10000	0	-1.1	188	188
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.67	0.49	1.1	249	-10000	0	249
CCL11	-0.59	0.43	-10000	0	-1	185	185
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.68	103	103
IL2RG	-0.044	0.19	-10000	0	-0.52	57	57
IL10	-0.62	0.47	-10000	0	-1.1	187	187
IRS1	-0.084	0.27	-10000	0	-0.82	59	59
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.095	-10000	0	-10000	0	0
IL5	-0.61	0.44	-10000	0	-1	206	206
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.49	0.33	-10000	0	-0.79	222	222
COL1A1	-0.26	0.23	-10000	0	-0.65	64	64
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.6	0.45	-10000	0	-1.1	173	173
IL2R gamma/JAK3	-0.081	0.18	-10000	0	-0.5	57	57
TFF3	-1.3	0.61	-10000	0	-1.6	412	412
ALOX15	-0.61	0.44	-10000	0	-1.1	179	179
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.52	0.36	-10000	0	-0.82	249	249
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	-0.64	99	99
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.67	99	99
PI3K	-0.34	0.28	-10000	0	-0.73	96	96
DOK2	-0.001	0.079	-10000	0	-0.82	2	2
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	-0.62	58	58
ITGB3	-0.62	0.47	-10000	0	-1.1	188	188
PIGR	-0.65	0.5	-10000	0	-1.2	194	194
IGHE	0.052	0.035	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.61	58	58
BCL6	0.012	0.037	-10000	0	-0.82	1	1
OPRM1	-0.61	0.44	-10000	0	-1	208	208
RETNLB	-0.61	0.44	-10000	0	-1.1	182	182
SELP	-0.61	0.45	-10000	0	-1.1	192	192
AICDA	-0.59	0.42	-10000	0	-1	184	184

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.46	311	311
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.003	0.056	-9999	-0.31	15	15
WNT4	-0.26	0.39	-9999	-0.81	166	166
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	257	257

×

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	152	152
PDGF/PDGFRA/CRKL	-0.19	0.29	-9999	-0.62	152	152
positive regulation of JUN kinase activity	-0.14	0.22	-9999	-0.48	152	152
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.2	0.29	-9999	-0.63	152	152
AP1	-0.48	0.62	-9999	-1.5	135	135
mol:IP3	-0.19	0.3	-9999	-0.65	152	152
PLCG1	-0.19	0.3	-9999	-0.65	152	152
PDGF/PDGFRA/alphaV Integrin	-0.19	0.29	-9999	-0.63	153	153
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	152	152
CAV3	-0.001	0.028	-9999	-0.31	4	4
CAV1	-0.008	0.13	-9999	-0.82	13	13
SHC/Grb2/SOS1	-0.15	0.22	-9999	-0.48	152	152
PDGF/PDGFRA/Shf	-0.19	0.29	-9999	-0.62	152	152
FOS	-0.44	0.6	-9999	-1.4	135	135
JUN	-0.17	0.28	-9999	-0.7	113	113
oligodendrocyte development	-0.19	0.29	-9999	-0.62	153	153
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.19	0.3	-9999	-0.65	152	152
PDGF/PDGFRA	-0.25	0.38	-9999	-0.83	152	152
actin cytoskeleton reorganization	-0.19	0.29	-9999	-0.62	152	152
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.16	0.25	-9999	-0.53	155	155
PDGF/PDGFRA/Crk/C3G	-0.16	0.25	-9999	-0.53	152	152
JAK1	-0.18	0.3	-9999	-0.62	152	152
ELK1/SRF	-0.12	0.24	-9999	-0.48	152	152
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	-0.19	0.31	-9999	-0.66	152	152
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.14	0.22	-9999	-0.48	152	152
PDGF/PDGFRA/SHB	-0.19	0.29	-9999	-0.62	152	152
PDGF/PDGFRA/Caveolin-1	-0.2	0.31	-9999	-0.66	155	155
ITGAV	0.01	0.052	-9999	-0.82	2	2
ELK1	-0.17	0.28	-9999	-0.59	152	152
PIK3CA	0.008	0.064	-9999	-0.82	3	3
PDGF/PDGFRA/Crk	-0.19	0.29	-9999	-0.62	152	152
JAK-STAT cascade	-0.18	0.3	-9999	-0.62	152	152
cell proliferation	-0.19	0.29	-9999	-0.62	152	152

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.51	0.54	-9999	-1.1	212	212
PCK1	-0.34	0.49	-9999	-1.5	62	62
HNF4A	-0.66	0.66	-9999	-1.3	249	249
KCNJ11	-0.48	0.54	-9999	-1.1	188	188
AKT1	-0.042	0.12	-9999	-0.4	5	5
response to starvation	-0.017	0.033	-9999	-10000	0	0
DLK1	-0.49	0.54	-9999	-1.1	193	193
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.51	0.54	-9999	-1	218	218
TAT	-0.2	0.22	-9999	-0.71	9	9
CEBPB	0.013	0.005	-9999	-10000	0	0
CEBPA	0.005	0.083	-9999	-0.82	5	5
TTR	-0.19	0.22	-9999	-0.76	28	28
PKLR	-0.52	0.54	-9999	-1.1	206	206
APOA1	-0.91	0.89	-9999	-1.7	258	258
CPT1C	-0.52	0.55	-9999	-1.1	216	216
ALAS1	-0.16	0.21	-9999	-10000	0	0
TFRC	-0.26	0.3	-9999	-0.73	52	52
FOXF1	-0.009	0.083	-9999	-0.74	6	6
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	-1.1	210	210
HMGCS1	-0.51	0.54	-9999	-1.1	207	207
NR3C1	0.019	0.018	-9999	-10000	0	0
CPT1B	-0.51	0.54	-9999	-1.1	206	206
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.66	0.7	-9999	-1.4	216	216
CREB1	0.001	0.052	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.55	14	14
PDX1	-0.18	0.21	-9999	-0.61	1	1
UCP2	-0.51	0.54	-9999	-1.1	213	213
ALDOB	-0.48	0.54	-9999	-1.1	192	192
AFP	-0.046	0.11	-9999	-0.45	17	17
BDH1	-0.51	0.54	-9999	-1.1	201	201
HADH	-0.48	0.54	-9999	-1.1	192	192
F2	-0.62	0.63	-9999	-1.3	209	209
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.006	0.09	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.57	18	18
INS	-0.012	0.066	-9999	-0.83	3	3
FOXA1	-0.055	0.14	-9999	-0.35	74	74
FOXA3	-0.073	0.17	-9999	-0.5	35	35
FOXA2	-0.55	0.61	-9999	-1.2	209	209
ABCC8	-0.78	0.75	-9999	-1.4	262	262
ALB	-0.096	0.32	-9999	-1.3	30	30

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.13	0.31	-9999	-0.82	87	87
GNB1/GNG2	-0.26	0.24	-9999	-0.61	121	121
mol:DAG	-0.21	0.24	-9999	-0.55	119	119
PLCG1	-0.22	0.24	-9999	-0.57	119	119
YES1	-0.25	0.26	-9999	-0.62	128	128
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.22	0.24	-9999	-0.58	119	119
MAP3K7	-0.17	0.2	-9999	-0.45	119	119
mol:Ca2+	-0.2	0.23	-9999	-0.53	119	119
mol:IP3	-0.21	0.24	-9999	-0.55	119	119
NLK	-0.01	0.01	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.19	0.22	-9999	-0.5	119	119
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.46	311	311
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.25	0.26	-9999	-0.62	128	128
GO:0007205	-0.21	0.23	-9999	-0.54	119	119
WNT6	0.003	0.056	-9999	-0.31	15	15
WNT4	-0.26	0.39	-9999	-0.81	166	166
NFAT1/CK1 alpha	-0.3	0.25	-9999	-0.62	152	152
GNG2	0.012	0.037	-9999	-0.82	1	1
WNT5A	-0.004	0.12	-9999	-0.77	11	11
WNT11	-0.41	0.41	-9999	-0.81	257	257
CDC42	-0.23	0.25	-9999	-0.6	118	118

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.21	0.25	-10000	0	-0.5	211	211
regulation of S phase of mitotic cell cycle	-0.12	0.18	-10000	0	-0.34	212	212
GNAO1	-0.016	0.15	-10000	0	-0.7	21	21
HRAS	0.012	0.021	-10000	0	-0.32	2	2
SHBG/T-DHT	-0.009	0.074	-10000	0	-0.56	9	9
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	210	210
T-DHT/AR	-0.27	0.32	-10000	0	-0.64	210	210
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	128	128
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.037	-10000	0	-0.82	1	1
mol:GDP	-0.26	0.3	-10000	0	-0.61	212	212
cell proliferation	-0.19	0.28	-10000	0	-0.54	138	138
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
FOS	-0.24	0.39	-10000	0	-0.89	128	128
mol:Ca2+	-0.027	0.03	-10000	0	-0.071	93	93
MAPK3	-0.18	0.26	-10000	0	-0.45	212	212
MAPK1	-0.081	0.13	-10000	0	-0.3	78	78
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	128	128
cAMP biosynthetic process	0.015	0.078	-10000	0	-0.52	9	9
GNG2	0.012	0.037	-10000	0	-0.82	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	128	128
HRAS/GTP	-0.2	0.23	-10000	0	-0.47	210	210
actin cytoskeleton reorganization	-0.003	0.034	-10000	0	-0.44	3	3
SRC	0.012	0.015	-10000	0	-0.32	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	128	128
PI3K	-0.003	0.042	-10000	0	-0.55	3	3
apoptosis	0.16	0.25	0.52	129	-10000	0	129
T-DHT/AR/PELP1	-0.23	0.27	-10000	0	-0.55	210	210
HRAS/GDP	-0.24	0.29	-10000	0	-0.58	211	211
CREB1	-0.17	0.27	-10000	0	-0.57	129	129
RAC1-CDC42/GTP	-0.003	0.035	-10000	0	-0.45	3	3
AR	-0.34	0.41	-10000	0	-0.82	210	210
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.17	0.24	-10000	0	-0.45	210	210
RAC1-CDC42/GDP	-0.23	0.27	-10000	0	-0.55	210	210
T-DHT/AR/PELP1/Src	-0.21	0.25	-10000	0	-0.51	210	210
MAP2K2	-0.16	0.23	-10000	0	-0.43	210	210
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.18	-10000	0	-0.34	212	212
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	-0.002	0.11	-10000	0	-0.82	9	9
Gi family/GNB1/GNG2/GDP	-0.019	0.12	-10000	0	-0.54	16	16
mol:T-DHT	0	0.001	0.002	76	-0.003	50	126
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.042	-10000	0	-0.5	3	3
Gi family/GTP	-0.094	0.12	-10000	0	-0.47	18	18
CDC42	0.013	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.11	0.26	-10000	0	-0.68	36	36
IHH	-0.2	0.36	-10000	0	-0.84	123	123
SHH Np/Cholesterol/GAS1	-0.1	0.2	-10000	0	-0.51	98	98
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.1	0.2	0.51	98	-10000	0	98
SMO/beta Arrestin2	-0.094	0.24	-10000	0	-0.49	85	85
SMO	-0.1	0.25	-10000	0	-0.51	127	127
AKT1	-0.026	0.12	-10000	0	-0.66	2	2
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	0	0.1	-10000	0	-0.82	8	8
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.1	0.25	-10000	0	-0.5	127	127
STIL	-0.076	0.2	-10000	0	-0.59	18	18
DHH N/PTCH2	-0.11	0.24	-10000	0	-0.64	83	83
DHH N/PTCH1	-0.098	0.22	-10000	0	-0.45	130	130
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
DHH	0.007	0.074	-10000	0	-0.82	4	4
PTHLH	-0.16	0.37	-10000	0	-1.2	36	36
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	36	36
IHH N/Hhip	-0.38	0.4	-10000	0	-0.73	265	265
DHH N/Hhip	-0.25	0.31	-10000	0	-0.63	197	197
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	197	197
HHAT	0.012	0.037	-10000	0	-0.82	1	1
PI3K	-0.004	0.048	-10000	0	-0.63	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.15	0.33	-10000	0	-0.82	97	97
somite specification	-0.1	0.25	-10000	0	-0.5	127	127
SHH Np/Cholesterol/PTCH1	-0.086	0.2	-10000	0	-0.62	17	17
SHH Np/Cholesterol/PTCH2	-0.087	0.19	-10000	0	-0.51	82	82
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.51	135	135
SHH	0.007	0.049	-10000	0	-0.63	1	1
catabolic process	-0.11	0.25	-10000	0	-0.51	126	126
SMO/Vitamin D3	-0.09	0.22	-10000	0	-0.65	17	17
SHH Np/Cholesterol/Hhip	-0.2	0.24	-10000	0	-0.51	196	196
LRP2	-0.21	0.37	-10000	0	-0.82	134	134
receptor-mediated endocytosis	-0.2	0.23	-10000	0	-0.72	49	49
SHH Np/Cholesterol/BOC	-0.014	0.073	-10000	0	-0.52	9	9
SHH Np/Cholesterol/CDO	-0.16	0.23	-10000	0	-0.51	149	149
mesenchymal cell differentiation	0.2	0.24	0.5	196	-10000	0	196
mol:Vitamin D3	-0.085	0.2	-10000	0	-0.62	17	17
IHH N/PTCH2	-0.23	0.34	-10000	0	-0.66	182	182
CDON	-0.23	0.38	-10000	0	-0.82	148	148
IHH N/PTCH1	-0.11	0.25	-10000	0	-0.51	126	126
Megalin/LRPAP1	-0.17	0.28	-10000	0	-0.63	134	134
PTCH2	-0.12	0.3	-10000	0	-0.82	81	81
SHH Np/Cholesterol	-0.006	0.035	-10000	0	-0.51	1	1
PTCH1	-0.11	0.25	-10000	0	-0.51	126	126
HHIP	-0.31	0.4	-10000	0	-0.81	197	197

×

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	-0.021	0.17	-9999	-0.82	21	21
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.42	0.26	-9999	-0.56	370	370
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.37	0.25	-9999	-0.51	370	370
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	-0.093	0.28	-9999	-0.82	64	64
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.026	0.12	-9999	-0.63	21	21
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	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	372	372
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.27	0.2	-9999	-0.69	19	19
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.32	0.23	-9999	-0.44	370	370
RELN	-0.59	0.37	-9999	-0.82	366	366
PAFAH/LIS1	-0.045	0.19	-9999	-0.54	64	64
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	17	17
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.24	0.18	-9999	-0.34	377	377
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.3	0.22	-9999	-0.42	370	370
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	-0.82	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	17	17
LRP8	-0.021	0.17	-9999	-0.82	21	21
NDEL1/Katanin 60	-0.27	0.2	-9999	-0.72	17	17
P39/CDK5	-0.32	0.23	-9999	-0.45	370	370
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.34	0.24	-9999	-0.47	370	370
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	372	372
RELN/VLDLR	-0.4	0.26	-9999	-0.53	376	376
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	87	87
NFATC3	0	0.027	-9999	-10000	0	0
CD40LG	-0.44	0.42	-9999	-0.88	205	205
PTGS2	-0.41	0.39	-9999	-0.85	186	186
JUNB	0.003	0.09	-9999	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.015	-9999	-10000	0	0
CALM1	0.008	0.008	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.82	113	113
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	-0.033	0.12	-9999	-0.32	69	69
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.59	170	170
FOS	-0.2	0.36	-9999	-0.82	128	128
IFNG	-0.44	0.41	-9999	-0.86	204	204
AP-1/NFAT1-c-4	-0.52	0.52	-9999	-1	216	216
FASLG	-0.42	0.39	-9999	-0.84	191	191
NFAT1-c-4/ICER1	-0.12	0.2	-9999	-0.5	95	95
IL2RA	-0.41	0.38	-9999	-0.84	186	186
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.36	-9999	-0.77	260	260
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.5	100	100
IL4	-0.39	0.36	-9999	-0.8	184	184
IL2	-0.012	0.026	-9999	-10000	0	0
IL3	-0.032	0.03	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.006	0.082	-9999	-0.33	28	28
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	0.69	121	-10000	0	121
KIRREL	-0.072	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	-0.076	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	-0.48	121	121
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.55	121	121
establishment of cell polarity	-0.17	0.3	-10000	0	-0.69	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	0.24	-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	-0.53	121	121
Nephrin/NEPH1/ZO-1	-0.14	0.26	-10000	0	-0.57	121	121

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.054	0.14	-9999	-0.56	11	11
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.67	70	70
EDN1	-0.045	0.12	-9999	-0.72	8	8
EDN3	-0.39	0.41	-9999	-0.81	247	247
EDN2	-0.014	0.11	-9999	-0.41	32	32
HRAS/GDP	-0.1	0.24	-9999	-0.51	96	96
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.086	0.18	-9999	-0.39	98	98
ADCY4	-0.098	0.2	-9999	-0.5	73	73
ADCY5	-0.16	0.25	-9999	-0.56	120	120
ADCY6	-0.098	0.2	-9999	-0.5	73	73
ADCY7	-0.098	0.2	-9999	-0.5	73	73
ADCY1	-0.1	0.21	-9999	-0.53	76	76
ADCY2	-0.14	0.24	-9999	-0.55	107	107
ADCY3	-0.098	0.2	-9999	-0.5	73	73
ADCY8	-0.2	0.21	-9999	-0.54	103	103
ADCY9	-0.098	0.2	-9999	-0.5	73	73
arachidonic acid secretion	-0.17	0.32	-9999	-0.62	145	145
ETB receptor/Endothelin-1/Gq/GTP	-0.098	0.22	-9999	-0.42	125	125
GNAO1	-0.016	0.15	-9999	-0.7	21	21
HRAS	0.01	0.021	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.019	0.16	-9999	-0.56	9	9
ETA receptor/Endothelin-1/Gs/GTP	-0.088	0.22	-9999	-0.53	74	74
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.071	0.18	-9999	-0.52	38	38
EDNRB	0.003	0.093	-9999	-0.75	7	7
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.16	0.24	-9999	-0.64	54	54
CYSLTR1	-0.064	0.18	-9999	-0.77	17	17
SLC9A1	-0.023	0.076	-9999	-0.36	3	3
mol:GDP	-0.12	0.26	-9999	-0.55	97	97
SLC9A3	-0.049	0.19	-9999	-0.81	21	21
RAF1	-0.15	0.3	-9999	-0.57	140	140
JUN	-0.28	0.51	-9999	-1.2	122	122
JAK2	-0.056	0.15	-9999	-0.59	12	12
mol:IP3	-0.11	0.23	-9999	-0.48	114	114
ETA receptor/Endothelin-1	-0.041	0.2	-9999	-0.56	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	-0.33	0.33	-9999	-0.66	246	246
FOS	-0.25	0.47	-9999	-1	130	130
Gai/GDP	-0.002	0.13	-9999	-0.66	16	16
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.13	0.24	-9999	-0.58	66	66
BCAR1	0.013	0.001	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.47	116	116
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.094	0.28	-9999	-0.82	65	65
Gs family/GDP	-0.19	0.25	-9999	-0.54	137	137
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.45	112	112
MAPK14	-0.065	0.18	-9999	-0.4	64	64
TRPC6	-0.14	0.3	-9999	-0.72	68	68
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.012	0.037	-9999	-0.82	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.077	0.19	-9999	-0.37	111	111
ETB receptor/Endothelin-2	-0.026	0.1	-9999	-0.63	12	12
ETB receptor/Endothelin-3	-0.32	0.32	-9999	-0.63	248	248
ETB receptor/Endothelin-1	-0.022	0.12	-9999	-0.63	13	13
MAPK3	-0.23	0.43	-9999	-0.89	136	136
MAPK1	-0.23	0.43	-9999	-0.89	137	137
Rac1/GDP	-0.1	0.24	-9999	-0.51	90	90
cAMP biosynthetic process	-0.14	0.21	-9999	-0.54	82	82
MAPK8	-0.18	0.35	-9999	-0.65	132	132
SRC	0.013	0.015	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.008	0.078	-9999	-0.35	10	10
p130Cas/CRK/Src/PYK2	-0.13	0.3	-9999	-0.54	137	137
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.51	90	90
COL1A2	-0.041	0.17	-9999	-0.7	10	10
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.49	14	14
mol:DAG	-0.11	0.23	-9999	-0.48	115	115
MAP2K2	-0.18	0.35	-9999	-0.69	139	139
MAP2K1	-0.18	0.35	-9999	-0.69	139	139
EDNRA	-0.039	0.099	-9999	-0.53	5	5
positive regulation of muscle contraction	-0.038	0.13	-9999	-0.53	9	9
Gq family/GDP	-0.19	0.29	-9999	-0.63	131	131
HRAS/GTP	-0.13	0.26	-9999	-0.52	119	119
PRKCH	-0.1	0.22	-9999	-0.47	109	109
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.25	-9999	-0.53	109	109
PRKCB	-0.12	0.23	-9999	-0.5	106	106
PRKCE	-0.11	0.24	-9999	-0.49	110	110
PRKCD	-0.1	0.22	-9999	-0.49	100	100
PRKCG	-0.11	0.23	-9999	-0.5	100	100
regulation of vascular smooth muscle contraction	-0.3	0.55	-9999	-1.2	130	130
PRKCQ	-0.11	0.23	-9999	-0.5	103	103
PLA2G4A	-0.19	0.36	-9999	-0.69	145	145
GNA14	-0.19	0.36	-9999	-0.82	120	120
GNA15	-0.015	0.093	-9999	-0.33	38	38
GNA12	0.013	0	-9999	-10000	0	0
GNA11	-0.006	0.12	-9999	-0.82	10	10
Rac1/GTP	-0.019	0.16	-9999	-0.54	10	10
MMP1	-0.092	0.16	-9999	-10000	0	0

×

Glypican 1 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	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	-0.049	0.22	-10000	0	-0.8	38	38
PRNP	0.012	0.037	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.094	0.22	-10000	0	-0.63	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	-0.047	0.16	-10000	0	-0.63	37	37
TDGF1	-0.34	0.41	-10000	0	-0.82	214	214
CRIPTO/GPC1	-0.27	0.31	-10000	0	-0.63	214	214
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	214	214
FLT1	0.012	0.037	-10000	0	-0.82	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	214	214
FGR	-0.22	0.28	-10000	0	-0.54	214	214
positive regulation of MAPKKK cascade	-0.28	0.31	-10000	0	-0.61	216	216
SLIT2	-0.11	0.3	-10000	0	-0.8	77	77
GPC1/NRG	-0.057	0.18	-10000	0	-0.63	45	45
NRG1	-0.062	0.24	-10000	0	-0.8	47	47
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.005	0.057	-10000	0	-0.7	3	3
LYN	-0.21	0.28	-10000	0	-0.54	214	214
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	214	214
TGFBR1	0.006	0.05	-10000	0	-0.31	12	12
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.25	0.36	-10000	0	-0.68	189	189
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	-0.82	3	3
BLK	-0.38	0.37	-10000	0	-0.66	290	290
HCK	-0.23	0.28	-10000	0	-0.55	214	214
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.012	0.037	-10000	0	-0.82	1	1
VEGFR1 homodimer	0.012	0.037	-10000	0	-0.82	1	1
TGFBR2	0.008	0.064	-10000	0	-0.82	3	3
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.004	0.03	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.19	0.27	-10000	0	-0.63	137	137
LCK	-0.23	0.28	-10000	0	-0.55	219	219
neuron differentiation	-0.057	0.18	-10000	0	-0.62	45	45
PrPc/Cu2+	-0.001	0.028	-10000	0	-0.64	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.008	0.064	-10000	0	-0.82	3	3

×

IGF1 pathway

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.12	0.23	-10000	0	-0.45	160	160
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	160	160
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.22	-10000	0	-0.52	114	114
AKT1	-0.089	0.21	-10000	0	-0.77	16	16
BAD	-0.076	0.2	-10000	0	-0.7	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.23	-10000	0	-0.45	160	160
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.24	-10000	0	-0.46	160	160
RAF1	-0.066	0.19	-10000	0	-0.65	16	16
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.21	-10000	0	-0.46	114	114
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.14	0.25	-10000	0	-0.49	160	160
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
RPS6KB1	-0.089	0.21	-10000	0	-0.42	115	115
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	-0.41	115	115
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.099	0.17	-10000	0	-0.42	114	114
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	160	160
Crk/p130 Cas/Paxillin	-0.13	0.2	-10000	0	-0.44	114	114
IGF1R	-0.019	0.048	-10000	0	-10000	0	0
IGF1	-0.19	0.35	-10000	0	-0.81	120	120
IRS2/Crk	-0.11	0.22	-10000	0	-0.42	160	160
PI3K	-0.14	0.22	-10000	0	-0.43	160	160
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	114	114
RAF1/14-3-3 E	-0.049	0.17	-10000	0	-0.53	16	16
BAD/14-3-3	-0.062	0.19	-10000	0	-0.62	16	16
PRKCZ	-0.089	0.21	-10000	0	-0.42	115	115
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	114	114
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.19	-10000	0	-0.46	114	114
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	160	160
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.13	0.24	-10000	0	-0.45	160	160
IRS1	-0.14	0.25	-10000	0	-0.49	160	160
IRS2	-0.12	0.23	-10000	0	-0.45	160	160
IGF-1R heterotetramer/IGF1	-0.16	0.27	-10000	0	-0.66	114	114
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.1	0.23	-10000	0	-0.44	115	115
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.1	0.24	-10000	0	-0.53	115	115
SHC1	0.013	0	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	205	205
Ephrin B2/EPHB1-2	-0.19	0.24	-10000	0	-0.5	192	192
neuron projection morphogenesis	-0.23	0.23	-10000	0	-0.5	205	205
Ephrin B1/EPHB1-2/Tiam1	-0.26	0.26	-10000	0	-0.56	205	205
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	-0.47	205	205
PI3K	0.003	0.12	-10000	0	-1	6	6
mol:GDP	-0.26	0.26	-10000	0	-0.55	205	205
ITGA2B	-0.074	0.26	-10000	0	-0.82	53	53
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.01	0.11	-10000	0	-1	6	6
MAP3K7	-0.011	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	-0.32	282	282
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.043	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	0.097	-10000	0	-0.89	6	6
SRC	-0.011	0.11	-10000	0	-1	6	6
ITGB3	-0.011	0.14	-10000	0	-0.82	15	15
EPHB1	-0.3	0.4	-10000	0	-0.82	190	190
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	-0.68	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	205	-10000	0	205
MAPK8	0.003	0.13	-10000	0	-0.78	12	12
Ephrin B1/EPHB1-2/RGS3	-0.18	0.24	-10000	0	-0.47	205	205
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	205	-10000	0	205
chemotaxis	0.18	0.24	0.46	205	-10000	0	205
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
Rac1/GTP	-0.24	0.24	-10000	0	-0.51	205	205
angiogenesis	-0.019	0.096	-10000	0	-0.89	6	6
LCK	-0.015	0.12	-10000	0	-1	6	6

×

HIF-1-alpha transcription factor 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	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	-0.29	0.34	-9999	-0.82	107	107
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.19	0.42	-9999	-0.91	68	68
AP1	-0.28	0.45	-9999	-0.92	152	152
ABCG2	-0.2	0.43	-9999	-0.93	69	69
HIF1A	-0.01	0.068	-9999	-10000	0	0
TFF3	-0.57	0.51	-9999	-1	206	206
GATA2	0.014	0.015	-9999	-0.31	1	1
AKT1	-0.039	0.1	-9999	-10000	0	0
response to hypoxia	-0.06	0.11	-9999	-0.24	20	20
MCL1	-0.19	0.42	-9999	-0.91	68	68
NDRG1	-0.19	0.42	-9999	-0.91	67	67
SERPINE1	-0.2	0.43	-9999	-0.93	69	69
FECH	-0.19	0.42	-9999	-0.91	67	67
FURIN	-0.19	0.42	-9999	-0.91	67	67
NCOA2	-0.065	0.24	-9999	-0.82	48	48
EP300	-0.064	0.18	-9999	-0.34	110	110
HMOX1	-0.2	0.42	-9999	-0.91	71	71
BHLHE40	-0.2	0.43	-9999	-0.95	63	63
BHLHE41	-0.19	0.42	-9999	-0.92	68	68
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	-0.82	113	113
RORA	-0.19	0.42	-9999	-0.93	67	67
ABCB1	-0.077	0.19	-9999	-1.4	8	8
TFRC	-0.19	0.42	-9999	-0.92	72	72
CXCR4	-0.19	0.42	-9999	-0.92	67	67
TF	-0.24	0.49	-9999	-1	92	92
CITED2	-0.22	0.47	-9999	-1	82	82
HIF1A/ARNT	-0.3	0.38	-9999	-1	71	71
LDHA	-0.039	0.05	-9999	-10000	0	0
ETS1	-0.19	0.42	-9999	-0.91	67	67
PGK1	-0.19	0.42	-9999	-0.91	67	67
NOS2	-0.21	0.43	-9999	-0.93	71	71
ITGB2	-0.2	0.42	-9999	-0.93	67	67
ALDOA	-0.19	0.42	-9999	-0.9	71	71
Cbp/p300/CITED2	-0.33	0.51	-9999	-1.1	108	108
FOS	-0.2	0.36	-9999	-0.82	128	128
HK2	-0.19	0.42	-9999	-0.92	69	69
SP1	0.022	0.007	-9999	-10000	0	0
GCK	-0.39	0.71	-9999	-1.5	139	139
HK1	-0.19	0.42	-9999	-0.9	71	71
NPM1	-0.19	0.42	-9999	-0.9	71	71
EGLN1	-0.19	0.42	-9999	-0.92	68	68
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.19	0.42	-9999	-0.92	66	66
SMAD3	0.015	0.003	-9999	-10000	0	0
EDN1	-0.16	0.31	-9999	-0.73	65	65
IGFBP1	-0.21	0.42	-9999	-0.9	77	77
VEGFA	-0.16	0.38	-9999	-0.76	75	75
HIF1A/JAB1	-0.011	0.021	-9999	-10000	0	0
CP	-0.35	0.55	-9999	-1	153	153
CXCL12	-0.24	0.48	-9999	-1	89	89
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.19	0.42	-9999	-0.92	63	63
EGLN3	-0.21	0.44	-9999	-0.93	77	77
CA9	-0.21	0.42	-9999	-0.93	68	68
TERT	-0.2	0.42	-9999	-0.92	71	71
ENO1	-0.19	0.42	-9999	-0.93	62	62
PFKL	-0.19	0.42	-9999	-0.91	67	67
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.23	0.44	-9999	-0.91	90	90
ARNT	-0.01	0.067	-9999	-10000	0	0
HNF4A	-0.025	0.064	-9999	-0.35	10	10
ADFP	-0.2	0.42	-9999	-0.91	71	71
SLC2A1	-0.16	0.38	-9999	-0.75	74	74
LEP	-0.2	0.42	-9999	-0.92	69	69
HIF1A/ARNT/Cbp/p300	-0.3	0.36	-9999	-0.85	112	112
EPO	-0.14	0.33	-9999	-0.89	33	33
CREBBP	-0.064	0.18	-9999	-0.34	112	112
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.82	104	104
PFKFB3	-0.19	0.42	-9999	-0.92	68	68
NT5E	-0.2	0.43	-9999	-0.92	71	71

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.21	0.55	-10000	0	-1.3	81	81
IL23A	-0.22	0.56	-10000	0	-1.3	87	87
NF kappa B1 p50/RelA/I kappa B alpha	-0.29	0.46	-10000	0	-1.2	89	89
positive regulation of T cell mediated cytotoxicity	-0.24	0.61	-10000	0	-1.4	91	91
ITGA3	-0.19	0.51	-10000	0	-1.2	82	82
IL17F	-0.1	0.34	-10000	0	-0.74	74	74
IL12B	-0.004	0.11	-10000	0	-0.59	14	14
STAT1 (dimer)	-0.23	0.58	-10000	0	-1.3	89	89
CD4	-0.19	0.5	-10000	0	-1.1	85	85
IL23	-0.23	0.53	-10000	0	-1.2	86	86
IL23R	-0.003	0.099	-10000	0	-10000	0	0
IL1B	-0.23	0.58	-10000	0	-1.3	81	81
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.19	0.5	-10000	0	-1.1	86	86
TYK2	0.014	0.023	-10000	0	-10000	0	0
STAT4	-0.024	0.14	-10000	0	-0.45	41	41
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.03	0.18	-10000	0	-0.8	25	25
IL12RB1	-0.024	0.13	-10000	0	-0.39	48	48
PIK3CA	0.009	0.064	-10000	0	-0.82	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	-1.4	91	91
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	87	87
ALOX12B	-0.21	0.51	-10000	0	-1.2	82	82
CXCL1	-0.22	0.53	-10000	0	-1.2	89	89
T cell proliferation	-0.24	0.61	-10000	0	-1.4	91	91
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.058	0.28	-10000	0	-0.58	63	63
PI3K	-0.3	0.48	-10000	0	-1.2	90	90
IFNG	-0.02	0.055	-10000	0	-0.13	75	75
STAT3 (dimer)	-0.28	0.44	-10000	0	-1.1	86	86
IL18R1	-0.029	0.14	-10000	0	-0.43	47	47
IL23/IL23R/JAK2/TYK2/SOCS3	-0.096	0.33	-10000	0	-0.74	62	62
IL18/IL18R	-0.068	0.18	-10000	0	-0.58	46	46
macrophage activation	-0.014	0.018	-10000	0	-0.044	95	95
TNF	-0.26	0.62	-10000	0	-1.4	103	103
STAT3/STAT4	-0.31	0.49	-10000	0	-1.2	92	92
STAT4 (dimer)	-0.24	0.58	-10000	0	-1.3	92	92
IL18	-0.039	0.15	-10000	0	-0.41	60	60
IL19	-0.19	0.5	-10000	0	-1.1	87	87
STAT5A (dimer)	-0.23	0.57	-10000	0	-1.3	91	91
STAT1	0.006	0.05	-10000	0	-0.31	12	12
SOCS3	-0.025	0.17	-10000	0	-0.8	24	24
CXCL9	-0.3	0.64	-10000	0	-1.4	113	113
MPO	-0.2	0.51	-10000	0	-1.1	89	89
positive regulation of humoral immune response	-0.24	0.61	-10000	0	-1.4	91	91
IL23/IL23R/JAK2/TYK2	-0.29	0.74	-10000	0	-1.6	91	91
IL6	-0.31	0.64	-10000	0	-1.3	124	124
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	87	87
keratinocyte proliferation	-0.24	0.61	-10000	0	-1.4	91	91
NOS2	-0.2	0.5	-10000	0	-1.1	85	85

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.26	0.32	-9999	-0.59	221	221
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.046	0.21	-9999	-0.7	42	42
SMAD9	-0.22	0.28	-9999	-0.59	162	162
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.094	0.2	-9999	-0.36	165	165
BMP7/USAG1	-0.32	0.31	-9999	-0.63	257	257
SMAD5/SKI	-0.082	0.19	-9999	-0.52	28	28
SMAD1	0.019	0.044	-9999	-10000	0	0
BMP2	-0.016	0.15	-9999	-0.82	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	-0.82	165	165
BMPR1A-1B/BAMBI	-0.18	0.26	-9999	-0.55	165	165
AHSG	-0.019	0.087	-9999	-0.31	40	40
CER1	0	0.002	-9999	-10000	0	0
BMP2-4/CER1	-0.036	0.13	-9999	-0.55	31	31
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.074	0.19	-9999	-0.61	32	32
BMP2-4 (homodimer)	-0.042	0.15	-9999	-0.63	31	31
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	165	165
RGMA	-0.018	0.16	-9999	-0.82	19	19
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.086	0.18	-9999	-0.56	30	30
BMP2-4/USAG1	-0.31	0.3	-9999	-0.57	273	273
SMAD6/SMURF1/SMAD5	-0.082	0.19	-9999	-0.52	28	28
SOSTDC1	-0.41	0.41	-9999	-0.81	258	258
BMP7/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	165	165
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	-0.046	0.15	-9999	-0.55	40	40
SMAD5/SMAD5/SMAD4	-0.082	0.19	-9999	-0.52	28	28
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.092	0.14	-9999	-0.48	30	30
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.018	0.059	-9999	-0.4	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	143	143
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.006	0.059	-9999	-0.54	6	6
BMPR1A-1B (homodimer)	-0.21	0.29	-9999	-0.63	165	165
CHRDL1	-0.57	0.38	-9999	-0.82	355	355
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	-0.58	361	361
BMP2-4/GREM1	-0.17	0.27	-9999	-0.59	134	134
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	-0.065	0.16	-9999	-0.49	30	30
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	0.09	-9999	-0.82	6	6
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.19	0.31	-9999	-0.79	86	86
CHRD	-0.003	0.12	-9999	-0.82	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.092	0.19	-9999	-0.6	30	30
BMP4	-0.013	0.14	-9999	-0.64	20	20
FST	-0.19	0.35	-9999	-0.78	129	129
BMP2-4/NOG	-0.073	0.18	-9999	-0.55	63	63
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.15	0.22	-9999	-0.46	165	165

×

Glucocorticoid receptor regulatory network

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
PCK2	0.046	0.094	-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	-0.16	0.28	-10000	0	-0.63	87	87
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	0.09	-10000	0	-0.82	6	6
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.34	44	-0.49	6	50
PRL	-0.088	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.24	0.31	0.59	154	-0.51	20	174
RELA	-0.029	0.087	-10000	0	-0.26	4	4
FGG	0.24	0.19	0.53	102	-10000	0	102
GR beta/TIF2	0.08	0.24	0.35	76	-0.56	48	124
IFNG	-0.49	0.51	-10000	0	-1.1	146	146
apoptosis	0.034	0.24	0.52	58	-0.54	3	61
CREB1	0.012	0.023	-10000	0	-10000	0	0
histone acetylation	-0.069	0.17	-10000	0	-0.39	68	68
BGLAP	-0.098	0.15	-10000	0	-0.53	11	11
GR/PKAc	0.13	0.1	0.34	38	-0.41	1	39
NF kappa B1 p50/RelA	-0.061	0.16	-10000	0	-0.44	30	30
SMARCD1	0.014	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.096	0.28	93	-10000	0	93
GATA3	-0.027	0.19	-10000	0	-0.78	28	28
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.59	33	33
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.061	0.23	0.52	40	-0.74	5	45
CSN2	0.2	0.14	0.44	63	-10000	0	63
BRG1/BAF155/BAF170/BAF60A	0.021	0.048	-10000	0	-10000	0	0
NFATC1	0.001	0.11	-10000	0	-0.82	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	-0.82	15	15
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.044	0.16	0.35	13	-0.49	13	26
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.078	0.44	0.49	44	-0.88	108	152
JUN	-0.33	0.31	-10000	0	-0.71	167	167
IL4	-0.13	0.18	-10000	0	-0.63	27	27
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	-0.84	179	179
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.35	31	-0.47	5	36
cortisol/GR alpha (monomer)	0.36	0.3	0.7	180	-10000	0	180
NCOA2	-0.066	0.24	-10000	0	-0.82	48	48
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.35	-10000	0	-0.84	128	128
AP-1/NFAT1-c-4	-0.55	0.48	-10000	0	-0.99	226	226
AFP	-0.22	0.22	-10000	0	-0.6	88	88
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.49	49	-10000	0	49
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	-0.83	184	184
KRT14	-0.24	0.18	-10000	0	-0.63	18	18
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.065	0.066	-10000	0	-0.28	1	1
HDAC1	0.011	0.005	-10000	0	-10000	0	0
HDAC2	0.031	0.013	-10000	0	-10000	0	0
AP-1	-0.56	0.49	-10000	0	-1	226	226
MAPK14	0.014	0.012	-10000	0	-10000	0	0
MAPK10	0.013	0.039	-10000	0	-0.82	1	1
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.53	0.52	-10000	0	-1.3	131	131
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	0.38	182	-10000	0	182
MAPK3	0.014	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	90	90
NFKB1	-0.031	0.096	-10000	0	-0.94	1	1
MAPK8	-0.19	0.21	-10000	0	-0.52	97	97
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.028	0.25	0.52	58	-0.57	3	61
BAX	0.029	0.034	-10000	0	-10000	0	0
POMC	-0.54	0.69	-10000	0	-1.5	150	150
EP300	0.066	0.066	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.33	0.24	0.6	170	-10000	0	170
proteasomal ubiquitin-dependent protein catabolic process	0.086	0.072	0.25	24	-10000	0	24
SGK1	0.1	0.22	-10000	0	-1.4	10	10
IL13	-0.3	0.25	-10000	0	-0.84	51	51
IL6	-0.37	0.52	-10000	0	-1.1	141	141
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.68	54	54
IL2	-0.36	0.27	-10000	0	-0.72	129	129
CDK5	0.013	0.007	-10000	0	-10000	0	0
PRKACB	0.012	0.037	-10000	0	-0.82	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.26	0.32	-10000	0	-0.73	105	105
CDK5R1/CDK5	0.007	0.025	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.023	0.12	-10000	0	-0.46	6	6
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.57	161	-10000	0	161
SMARCA4	0.014	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.41	112	-0.39	1	113
NF kappa B1 p50/RelA/Cbp	0.029	0.16	-10000	0	-0.45	10	10
JUN (dimer)	-0.33	0.3	-10000	0	-0.7	167	167
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.42	-10000	0	-1.1	92	92
NR3C1	0.22	0.19	0.5	122	-10000	0	122
NR4A1	-0.31	0.41	-10000	0	-0.74	219	219
TIF2/SUV420H1	-0.06	0.18	-10000	0	-0.63	48	48
MAPKKK cascade	0.034	0.24	0.52	58	-0.54	3	61
cortisol/GR alpha (dimer)/Src-1	0.32	0.24	0.6	170	-10000	0	170
PBX1	0.012	0.037	-10000	0	-0.82	1	1
POU1F1	0.007	0.008	-10000	0	-10000	0	0
SELE	-0.33	0.49	-10000	0	-1.2	100	100
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.41	112	-0.4	1	113
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.57	161	-10000	0	161
mol:cortisol	0.21	0.2	0.41	190	-10000	0	190
MMP1	-0.21	0.15	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

Figure S25. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S25. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.62	77	77
FYN	-0.11	0.35	-10000	0	-0.82	81	81
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.67	87	87
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.055	0.22	-10000	0	-0.48	86	86
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.05	-10000	0	-0.19	14	14
MAP3K8	0.002	0.097	-10000	0	-0.82	7	7
mol:Ca2+	-0.031	0.05	-10000	0	-0.12	110	110
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.1	0.32	-10000	0	-0.74	89	89
TRPV6	-0.18	0.34	-10000	0	-0.8	112	112
CD28	-0.045	0.19	-10000	0	-0.59	48	48
SHC1	-0.11	0.34	-10000	0	-0.8	85	85
receptor internalization	-0.14	0.38	-10000	0	-0.83	95	95
PRF1	-0.11	0.35	-10000	0	-0.92	68	68
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.037	0.18	-10000	0	-0.39	83	83
LAT	-0.12	0.35	-10000	0	-0.82	85	85
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.092	0.27	-10000	0	-0.7	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	-0.19	6	6
RASGRP1	-0.051	0.22	-10000	0	-0.47	93	93
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	0.01	0.068	-10000	0	-0.12	59	59
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.057	0.091	-10000	0	-0.27	50	50
PRKCA	-0.059	0.13	-10000	0	-0.31	82	82
GRAP2	-0.045	0.21	-10000	0	-0.82	33	33
mol:IP3	-0.052	0.23	0.27	86	-0.48	80	166
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	0.088	0.16	0.39	105	-10000	0	105
CSK	-0.12	0.35	-10000	0	-0.83	85	85
B7 family/CD28	-0.2	0.35	-10000	0	-0.82	97	97
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.15	0.42	-10000	0	-0.98	87	87
PTPN6	-0.12	0.36	-10000	0	-0.84	84	84
VAV1	-0.12	0.34	-10000	0	-0.79	90	90
Monovalent TCR/CD3	-0.16	0.4	-10000	0	-0.73	121	121
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.86	82	82
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	-0.15	0.42	-10000	0	-0.98	87	87
CD80	-0.071	0.25	-10000	0	-0.8	52	52
CD86	-0.009	0.1	-10000	0	-0.41	26	26
PDK1/CARD11/BCL10/MALT1	-0.069	0.11	-10000	0	-0.32	59	59
HRAS	0.012	0.021	-10000	0	-0.31	2	2
GO:0035030	-0.11	0.29	-10000	0	-0.64	97	97
CD8A	-0.051	0.22	-10000	0	-0.81	39	39
CD8B	-0.089	0.27	-10000	0	-0.72	71	71
PTPRC	-0.035	0.18	-10000	0	-0.59	39	39
PDK1/PKC theta	-0.069	0.27	-10000	0	-0.6	85	85
CSK/PAG1	-0.11	0.34	-10000	0	-0.83	80	80
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	-0.79	88	88
STIM1	0.047	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.091	-10000	0	-0.18	56	56
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.43	-10000	0	-0.95	93	93
mol:DAG	-0.071	0.18	-10000	0	-0.42	87	87
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	-0.07	5	5
mol:PI-3-4-5-P3	-0.074	0.26	-10000	0	-0.58	89	89
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.081	0.29	0.3	77	-0.64	81	158
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.026	0.16	-10000	0	-0.62	31	31
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.25	-10000	0	-0.63	89	89
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.01	0.052	-10000	0	-0.82	2	2
CD8 heterodimer	-0.1	0.29	-10000	0	-0.75	77	77
CARD11	-0.07	0.17	-10000	0	-0.37	110	110
PRKCB	-0.058	0.13	-10000	0	-0.32	77	77
PRKCE	-0.052	0.12	-10000	0	-0.3	73	73
PRKCQ	-0.092	0.31	-10000	0	-0.7	87	87
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	-0.041	0.18	-10000	0	-0.4	86	86
IKK complex	0.014	0.068	-10000	0	-0.12	48	48
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.017	0.14	-10000	0	-0.3	65	65
PDPK1	-0.048	0.21	-10000	0	-0.46	85	85
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.45	-10000	0	-1.1	85	85

×

Glypican 2 network

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
MDK	-0.087	0.15	-9999	-0.32	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	-0.075	0.11	-9999	-0.41	13	13

×

Arf6 signaling events

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	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	0.082	-9999	-0.82	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	-0.099	0.23	-9999	-0.63	77	77
ARRB2	-0.045	0.15	-9999	-0.45	62	62
mol:GTP	0.02	0.012	-9999	-10000	0	0
ARRB1	0.012	0.037	-9999	-0.82	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.01	0.052	-9999	-0.82	2	2
EGF	-0.11	0.29	-9999	-0.78	78	78
somatostatin receptor activity	0	0	-9999	-0.001	151	151
ARAP2	0.01	0.052	-9999	-0.82	2	2
mol:GDP	-0.12	0.14	-9999	-0.29	157	157
mol:PI-3-4-5-P3	0	0	-9999	-0.001	126	126
ITGA2B	-0.074	0.26	-9999	-0.82	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	75	75
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.31	149	149
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.085	0.2	-9999	-0.54	77	77
ADRB2	-0.007	0.13	-9999	-0.82	12	12
receptor agonist activity	0	0	-9999	0	168	168
actin filament binding	0	0	-9999	-0.001	149	149
SRC	0.013	0.015	-9999	-0.31	1	1
ITGB3	-0.012	0.14	-9999	-0.82	15	15
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	142	142
ARF6/GDP	0	0.069	-9999	-0.33	2	2
ARF6/GDP/GULP/ACAP1	-0.19	0.2	-9999	-0.49	119	119
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.066	0.18	-9999	-0.54	62	62
ACAP1	-0.001	0.079	-9999	-0.37	19	19
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.079	0.22	-9999	-0.67	62	62
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.11	0.3	-9999	-0.82	75	75
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	146	146
endosomal lumen acidification	0	0	-9999	-0.001	161	161
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.32	-9999	-0.82	91	91
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	53	53
MET	-0.11	0.16	-9999	-0.31	182	182
GNA14	-0.19	0.35	-9999	-0.82	120	120
GNA15	-0.013	0.093	-9999	-0.33	38	38
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	147	147
GNA11	-0.003	0.12	-9999	-0.82	10	10
LHCGR	-0.099	0.27	-9999	-0.77	69	69
AGTR1	-0.32	0.41	-9999	-0.81	203	203
desensitization of G-protein coupled receptor protein signaling pathway	-0.079	0.22	-9999	-0.67	62	62
IPCEF1/ARNO	-0.057	0.16	-9999	-0.43	77	77
alphaIIb/beta3 Integrin	-0.084	0.23	-9999	-0.68	62	62

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.015	0.065	-10000	0	-0.35	14	14
SVIL	-0.007	0.031	-10000	0	-10000	0	0
ZNF318	0.062	0.092	0.24	1	-0.82	1	2
JMJD2C	-0.065	0.069	-10000	0	-0.12	288	288
T-DHT/AR/Ubc9	-0.28	0.3	-10000	0	-0.62	210	210
CARM1	0.012	0.003	-10000	0	-10000	0	0
PRDX1	0.015	0.004	-10000	0	-10000	0	0
PELP1	0.02	0.011	-10000	0	-10000	0	0
CTNNB1	-0.002	0.023	-10000	0	-10000	0	0
AKT1	0.026	0.02	-10000	0	-10000	0	0
PTK2B	0.004	0.015	-10000	0	-10000	0	0
MED1	0.025	0.019	-10000	0	-10000	0	0
MAK	0.052	0.13	0.21	30	-0.8	7	37
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.06	-10000	0	-0.82	2	2
GSN	-0.006	0.03	-10000	0	-10000	0	0
NCOA2	-0.068	0.24	-10000	0	-0.82	48	48
NCOA6	-0.007	0.046	-10000	0	-0.82	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	0.023	-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	219	219
FHL2	-0.16	0.36	-10000	0	-1.3	39	39
RANBP9	-0.005	0.029	-10000	0	-10000	0	0
JMJD1A	0.003	0.037	-10000	0	-0.12	37	37
CDK6	0.01	0.064	-10000	0	-0.82	3	3
TGFB1I1	-0.007	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.29	0.3	-10000	0	-0.63	211	211
XRCC6	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR	-0.33	0.31	-10000	0	-0.63	237	237
CTDSP1	0.009	0.006	-10000	0	-10000	0	0
CTDSP2	0.047	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	138	138
SRF	0.028	0.04	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-0.87	8	8
KLK3	-0.44	0.71	-10000	0	-1.6	144	144
TMF1	0.006	0.052	-10000	0	-0.82	2	2
HNRNPA1	0.032	0.028	-10000	0	-10000	0	0
AOF2	-0.022	0.034	-10000	0	-0.075	144	144
APPL1	0.052	0.043	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.27	0.29	-10000	0	-0.61	210	210
AR	-0.38	0.42	-10000	0	-0.86	210	210
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	210	210
RPS6KA3	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.28	0.29	-10000	0	-0.62	210	210
LATS2	0.03	0.047	-10000	0	-0.82	1	1
T-DHT/AR/PRX1	-0.24	0.28	-10000	0	-0.56	210	210
Cyclin D3/CDK11 p58	0.001	0.004	-10000	0	-10000	0	0
VAV3	-0.012	0.092	-10000	0	-0.82	6	6
KLK2	-0.78	0.62	-10000	0	-1.3	288	288
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.67	217	217
TMPRSS2	-0.18	0.31	-10000	0	-1.2	36	36
CCND1	0.001	0.05	-10000	0	-10000	0	0
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.032	0.041	-10000	0	-0.082	171	171
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.036	0.077	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.28	0.3	-10000	0	-0.62	212	212
CMTM2	0.014	0.026	-10000	0	-0.31	3	3
SNURF	-0.037	0.2	-10000	0	-0.82	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

×

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	-0.046	0.21	-9999	-0.7	42	42
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.16	-9999	-0.48	52	52
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.092	0.16	-9999	-0.56	30	30
Syndecan-1/Syntenin	-0.092	0.16	-9999	-0.45	51	51
MAPK3	-0.069	0.14	-9999	-0.6	19	19
HGF/MET	-0.16	0.24	-9999	-0.68	75	75
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	-0.09	0.15	-9999	-0.55	30	30
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.62	62	62
Syndecan-1/CD147	-0.081	0.15	-9999	-0.58	25	25
Syndecan-1/Syntenin/PIP2	-0.099	0.14	-9999	-0.47	42	42
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.097	0.14	-9999	-0.46	42	42
MMP7	-0.18	0.22	-9999	-0.37	246	246
HGF	-0.11	0.3	-9999	-0.82	75	75
Syndecan-1/CASK	-0.1	0.16	-9999	-0.46	52	52
Syndecan-1/HGF/MET	-0.2	0.24	-9999	-0.6	99	99
regulation of cell adhesion	-0.059	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	52	52
SDC1	-0.1	0.16	-9999	-0.48	52	52
Syndecan-1/Collagen	-0.1	0.16	-9999	-0.48	52	52
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.1	0.16	-9999	-0.31	182	182
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.085	0.24	-9999	-0.58	83	83
MAPK1	-0.069	0.14	-9999	-0.6	19	19
homophilic cell adhesion	-0.1	0.16	-9999	-0.47	52	52
MMP1	-0.14	0.16	-9999	-0.31	230	230

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.086	0.2	-10000	0	-0.56	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	-0.82	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.081	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.21	0.27	-10000	0	-0.55	190	190
HRAS/GDP	-0.13	0.17	-10000	0	-0.39	62	62
Ephrin B/EPHB1/GRB7	-0.21	0.24	-10000	0	-0.5	195	195
Endophilin/SYNJ1	0.026	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	195	195
endothelial cell migration	-0.003	0.036	-10000	0	-0.46	3	3
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.041	0.12	-10000	0	-0.31	84	84
PAK1	0.034	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	-0.79	17	17
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.15	0.24	-10000	0	-0.45	195	195
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	-0.33	190	190
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.064	-10000	0	-0.82	3	3
EPHB3	-0.19	0.16	-10000	0	-0.31	305	305
EPHB1	-0.3	0.4	-10000	0	-0.82	190	190
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.067	0.17	-10000	0	-0.46	11	11
Ephrin B/EPHB2	-0.014	0.068	-10000	0	-0.47	10	10
Ephrin B/EPHB3	-0.086	0.086	-10000	0	-0.57	7	7
JNK cascade	-0.15	0.24	-10000	0	-0.45	192	192
Ephrin B/EPHB1	-0.19	0.23	-10000	0	-0.48	195	195
RAP1/GDP	-0.051	0.15	-10000	0	-0.49	4	4
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	192	192
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	-0.57	11	11
Rap1/GTP	-0.15	0.18	-10000	0	-0.55	11	11
axon guidance	-0.085	0.2	-10000	0	-0.55	77	77
MAPK3	-0.076	0.16	-10000	0	-0.53	2	2
MAPK1	-0.076	0.16	-10000	0	-0.38	11	11
Rac1/GDP	-0.042	0.17	-10000	0	-0.46	7	7
actin cytoskeleton reorganization	-0.1	0.13	-10000	0	-0.45	6	6
CDC42/GDP	-0.042	0.17	-10000	0	-0.46	7	7
PI3K	-0.003	0.036	-10000	0	-0.47	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	-0.53	12	12
PTK2	0.041	0.052	-10000	0	-10000	0	0
MAP4K4	-0.15	0.24	-10000	0	-0.46	192	192
SRC	0.013	0.015	-10000	0	-0.31	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.066	0.18	-10000	0	-0.54	3	3
MAP2K1	-0.089	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	192	192
cell migration	-0.084	0.19	-10000	0	-0.42	13	13
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.026	0.071	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.022	0.17	-10000	0	-0.44	63	63
HRAS/GTP	-0.16	0.2	-10000	0	-0.4	197	197
Ephrin B1/EPHB1-2	-0.19	0.24	-10000	0	-0.5	192	192
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	197	197
RAC1-CDC42/GTP	-0.2	0.21	-10000	0	-0.49	146	146
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.051	0.15	-10000	0	-0.52	3	3
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	-0.074	0.081	-10000	0	-10000	0	0
RAS family/GDP	-0.082	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	-0.34	195	195

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.084	0.063	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.14	0.18	-9999	-0.65	44	44
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.61	73	73
Syndecan-4/ADAM12	-0.17	0.19	-9999	-0.64	46	46
CCL5	-0.046	0.21	-9999	-0.7	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	-0.3	6	6
ADAM12	-0.068	0.14	-9999	-0.31	125	125
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.064	0.043	-9999	-0.23	5	5
Syndecan-4/Laminin alpha1	-0.17	0.21	-9999	-0.68	53	53
Syndecan-4/CXCL12/CXCR4	-0.17	0.23	-9999	-0.65	73	73
Syndecan-4/Laminin alpha3	-0.16	0.2	-9999	-0.66	49	49
MDK	-0.087	0.15	-9999	-0.32	152	152
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.64	46	46
Syndecan-4/Midkine	-0.18	0.2	-9999	-0.66	46	46
FZD7	0.007	0.074	-9999	-0.82	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.6	45	45
THBS1	-0.019	0.097	-9999	-0.31	49	49
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.66	45	45
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.61	73	73
Syndecan-4/TACI	-0.26	0.26	-9999	-0.63	137	137
CXCR4	0.011	0.025	-9999	-0.31	3	3
cell adhesion	-0.064	0.091	-9999	-0.45	19	19
Syndecan-4/Dynamin	-0.14	0.18	-9999	-0.65	44	44
Syndecan-4/TSP1	-0.15	0.19	-9999	-0.65	45	45
Syndecan-4/GIPC	-0.14	0.18	-9999	-0.65	44	44
Syndecan-4/RANTES	-0.17	0.23	-9999	-0.74	53	53
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.049	0.22	-9999	-0.8	38	38
LAMA3	-0.025	0.16	-9999	-0.57	33	33
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.023	0.15	-9999	-0.74	19	19
Syndecan-4/alpha-Actinin	-0.14	0.18	-9999	-0.65	44	44
TFPI	-0.033	0.19	-9999	-0.82	28	28
F2	-0.007	0.053	-9999	-0.31	14	14
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.18	0.21	-9999	-0.66	58	58
ACTN1	0.013	0.015	-9999	-0.31	1	1
TNC	-0.11	0.17	-9999	-0.33	184	184
Syndecan-4/CXCL12	-0.18	0.24	-9999	-0.68	73	73
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.074	0.26	-9999	-0.82	53	53
TNFRSF13B	-0.2	0.36	-9999	-0.79	133	133
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.012	0.037	-9999	-0.82	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.66	44	44
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	364	364
cell migration	-0.021	0.017	-9999	-10000	0	0
PRKCD	0.008	0.014	-9999	-10000	0	0
vasculogenesis	-0.15	0.18	-9999	-0.62	45	45
SDC4	-0.15	0.19	-9999	-0.7	44	44
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.69	45	45
Syndecan-4/PI-4-5-P2/PKC alpha	-0.051	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.14	0.18	-9999	-0.65	44	44
MMP9	-0.087	0.24	-9999	-0.58	82	82
Rac1/GTP	-0.071	0.087	-9999	-0.46	19	19
cytoskeleton organization	-0.13	0.17	-9999	-0.62	44	44
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.21	-9999	-0.65	62	62

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.027	0.16	-10000	0	-0.43	35	35
TBX21	-0.12	0.44	-10000	0	-1.1	68	68
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	-0.091	0.38	-10000	0	-0.95	58	58
IL12RB2	-0.014	0.16	-10000	0	-0.72	21	21
GADD45G	-0.075	0.34	-10000	0	-0.92	45	45
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	-0.41	60	60
IL2RA	-0.047	0.2	-10000	0	-0.6	50	50
IFNG	-0.11	0.28	-10000	0	-0.72	81	81
STAT3 (dimer)	-0.074	0.32	-10000	0	-0.74	68	68
HLA-DRB5	-0.041	0.13	-10000	0	-0.35	72	72
FASLG	-0.14	0.48	-10000	0	-1.2	70	70
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.84	73	73
CD4	-0.001	0.063	-10000	0	-0.32	19	19
SOCS1	0.008	0.049	-10000	0	-0.4	6	6
EntrezGene:6955	-0.006	0.015	-10000	0	-10000	0	0
CD3D	-0.096	0.27	-10000	0	-0.7	75	75
CD3E	-0.071	0.24	-10000	0	-0.74	54	54
CD3G	-0.15	0.32	-10000	0	-0.78	99	99
IL12Rbeta2/JAK2	-0.001	0.13	-10000	0	-0.63	19	19
CCL3	-0.11	0.43	-10000	0	-1.1	57	57
CCL4	-0.15	0.51	-10000	0	-1.3	66	66
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
IL18/IL18R	-0.032	0.2	-10000	0	-0.57	48	48
NOS2	-0.089	0.34	-10000	0	-0.88	51	51
IL12/IL12R/TYK2/JAK2/SPHK2	-0.025	0.15	-10000	0	-0.43	31	31
IL1R1	-0.088	0.37	-10000	0	-0.97	52	52
IL4	0.002	0.023	-10000	0	-10000	0	0
JAK2	0.012	0.057	-10000	0	-0.83	2	2
EntrezGene:6957	-0.006	0.014	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.56	-10000	0	-1.1	108	108
RAB7A	-0.042	0.29	-10000	0	-0.68	51	51
lysosomal transport	-0.037	0.28	-10000	0	-0.65	52	52
FOS	-0.4	0.65	-10000	0	-1.3	160	160
STAT4 (dimer)	-0.08	0.35	-10000	0	-0.82	64	64
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.87	96	96
GZMA	-0.11	0.41	-10000	0	-1	61	61
GZMB	-0.1	0.39	-10000	0	-0.99	57	57
HLX	0.004	0.054	-10000	0	-0.31	14	14
LCK	-0.11	0.42	-10000	0	-1	68	68
TCR/CD3/MHC II/CD4	-0.18	0.35	-10000	0	-0.74	103	103
IL2/IL2R	-0.081	0.22	-10000	0	-0.67	48	48
MAPK14	-0.07	0.35	-10000	0	-0.8	64	64
CCR5	-0.099	0.4	-10000	0	-1	58	58
IL1B	-0.043	0.22	-10000	0	-0.8	36	36
STAT6	-0.005	0.11	-10000	0	-0.25	13	13
STAT4	-0.024	0.14	-10000	0	-0.45	41	41
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	-0.82	1	1
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.004	0.11	-10000	0	-0.58	14	14
CD8A	-0.051	0.22	-10000	0	-0.81	39	39
CD8B	-0.09	0.26	-10000	0	-0.72	71	71
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.026	0.16	0.43	35	-10000	0	35
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	63	63
IL2RG	-0.048	0.19	-10000	0	-0.52	57	57
IL12	-0.06	0.22	-10000	0	-0.64	59	59
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	-0.075	0.26	-10000	0	-0.8	56	56
IL12/IL12R/TYK2/JAK2	-0.13	0.48	-10000	0	-1	75	75
MAP2K3	-0.072	0.34	-10000	0	-0.8	62	62
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.078	0.35	-10000	0	-0.82	65	65
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	-0.026	0.18	-10000	0	-0.78	26	26
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)	-0.14	0.37	-10000	0	-0.79	93	93
T cell proliferation	-0.05	0.27	-10000	0	-0.6	59	59
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.025	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	-0.68	65	65
ATF2	-0.075	0.33	-10000	0	-0.74	64	64

×

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	-0.32	0.28	-9999	-0.55	261	261
GNAO1	-0.02	0.15	-9999	-0.7	21	21
SMO/beta Arrestin2	0.012	0.031	-9999	-0.62	1	1
SMO	0.006	0.038	-9999	-0.82	1	1
ARRB2	0.008	0.007	-9999	-10000	0	0
GLI3/SPOP	0.045	0.055	-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	-0.83	1	1
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.24	0.19	-9999	-0.51	136	136
SAP30	0.013	0.037	-9999	-0.82	1	1
mol:GDP	0.006	0.038	-9999	-0.82	1	1
MIM/GLI2A	-0.007	0.043	-9999	-0.31	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GLI2	0.034	0.06	-9999	-10000	0	0
GLI3	0.039	0.058	-9999	-10000	0	0
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.012	0.037	-9999	-0.82	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	242	242
neural tube patterning	-0.32	0.28	-9999	-0.55	261	261
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.022	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	-0.007	0.043	-9999	-0.31	1	1
embryonic limb morphogenesis	-0.32	0.28	-9999	-0.55	261	261
SUFU	0.016	0.021	-9999	-10000	0	0
LGALS3	-0.092	0.16	-9999	-0.32	160	160
catabolic process	0.061	0.067	-9999	-10000	0	0
GLI3A/CBP	-0.19	0.2	-9999	-0.38	260	260
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.32	0.29	-9999	-0.57	261	261
RAB23	0.007	0.074	-9999	-0.82	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.03	0.08	-9999	-0.45	2	2
GNAZ	0.01	0.006	-9999	-10000	0	0
RBBP4	0.009	0.064	-9999	-0.82	3	3
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.056	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.013	0.062	-9999	-0.42	2	2
PTCH1	-0.28	0.27	-9999	-0.62	136	136
MIM/GLI1	-0.45	0.39	-9999	-0.75	256	256
CREBBP	-0.19	0.2	-9999	-0.38	260	260
Su(fu)/SIN3/HDAC complex	0.056	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	-0.54	18	18
alphaM/beta2 Integrin/GPIbA	-0.053	0.14	-9999	-0.49	38	38
alphaM/beta2 Integrin/proMMP-9	-0.093	0.2	-9999	-0.59	57	57
PLAUR	-0.091	0.15	-9999	-0.31	160	160
HMGB1	0.003	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.033	0.098	-9999	-0.52	11	11
AGER	-0.056	0.21	-9999	-0.78	38	38
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.009	0.083	-9999	-0.31	35	35
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.11	0.19	-9999	-0.61	45	45
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.085	0.24	-9999	-0.58	83	83
CYR61	-0.24	0.38	-9999	-0.82	151	151
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.069	0.088	-9999	-0.4	11	11
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.002	0.1	-9999	-0.58	13	13
MYH2	-0.1	0.12	-9999	-0.39	39	39
MST1R	0	0.096	-9999	-0.59	11	11
leukocyte activation during inflammatory response	-0.039	0.092	-9999	-0.52	7	7
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	-0.018	0.15	-9999	-0.62	25	25
alphaM/beta2 Integrin/CTGF	-0.12	0.22	-9999	-0.56	94	94
alphaM/beta2 Integrin	-0.092	0.11	-9999	-0.34	47	47
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.066	0.14	-9999	-0.31	122	122
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.091	0.11	-9999	-0.34	47	47
cell adhesion	-0.052	0.14	-9999	-0.49	38	38
NFKB1	-0.12	0.29	-9999	-0.71	65	65
THY1	0.011	0.029	-9999	-0.31	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.014	0.049	-9999	-0.34	2	2
alphaM/beta2 Integrin/LRP/tPA	-0.033	0.1	-9999	-0.58	9	9
IL6	-0.21	0.44	-9999	-1	96	96
ITGB2	-0.018	0.087	-9999	-0.34	30	30
elevation of cytosolic calcium ion concentration	-0.14	0.16	-9999	-0.51	39	39
alphaM/beta2 Integrin/JAM2/JAM3	-0.031	0.099	-9999	-0.59	9	9
JAM2	0.006	0.075	-9999	-0.72	5	5
alphaM/beta2 Integrin/ICAM1	-0.06	0.12	-9999	-0.5	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.099	0.12	-9999	-0.51	20	20
RhoA/GTP	-0.1	0.12	-9999	-0.4	41	41
positive regulation of phagocytosis	-0.068	0.12	-9999	-0.49	16	16
Ron/MSP	-0.011	0.076	-9999	-0.63	7	7
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.16	-9999	-0.51	39	39
alphaM/beta2 Integrin/uPAR	-0.084	0.13	-9999	-0.45	35	35
PLAU	-0.14	0.16	-9999	-0.31	235	235
PLAT	0.003	0.076	-9999	-0.45	11	11
actin filament polymerization	-0.096	0.11	-9999	-0.37	39	39
MST1	0.011	0.04	-9999	-0.56	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.039	0.094	-9999	-0.62	5	5
TNF	-0.17	0.39	-9999	-0.98	80	80
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.13	-9999	-0.53	22	22
fibrinolysis	-0.098	0.12	-9999	-0.51	20	20
HCK	-0.01	0.084	-9999	-0.31	36	36
dendritic cell antigen processing and presentation	-0.091	0.11	-9999	-0.34	47	47
VTN	-0.066	0.24	-9999	-0.75	52	52
alphaM/beta2 Integrin/CYR61	-0.2	0.27	-9999	-0.57	165	165
LPA	-0.002	0.043	-9999	-0.31	9	9
LRP1	0.012	0.037	-9999	-0.82	1	1
cell migration	-0.09	0.2	-9999	-0.57	59	59
FN1	-0.22	0.15	-9999	-0.31	364	364
alphaM/beta2 Integrin/Thy1	-0.034	0.099	-9999	-0.52	11	11
MPO	0	0.093	-9999	-0.65	9	9
KNG1	-0.014	0.078	-9999	-0.31	32	32
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.091	0.11	-9999	-0.38	38	38
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.04	-9999	-0.31	8	8
CTGF	-0.11	0.3	-9999	-0.82	77	77
alphaM/beta2 Integrin/Hck	-0.045	0.12	-9999	-0.45	35	35
ITGAM	-0.022	0.11	-9999	-0.39	32	32
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.046	0.13	-9999	-0.52	26	26
HP	-0.083	0.16	-9999	-0.34	137	137
leukocyte adhesion	-0.086	0.15	-9999	-0.6	26	26
SELP	-0.002	0.1	-9999	-0.58	13	13

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.05	0.21	-10000	0	-0.66	20	20
CRP	-0.056	0.21	-10000	0	-0.67	21	21
cell cycle arrest	-0.071	0.23	-10000	0	-0.72	31	31
TIMP1	-0.15	0.22	-10000	0	-0.6	38	38
IL6ST	-0.11	0.29	-10000	0	-0.82	72	72
Rac1/GDP	-0.078	0.24	-10000	0	-0.61	58	58
AP1	-0.19	0.32	-10000	0	-0.71	119	119
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.092	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	-0.084	0.29	-10000	0	-0.78	55	55
AKT1	0.053	0.056	-10000	0	-1.1	1	1
FOXO1	0.06	0.052	-10000	0	-0.98	1	1
MAP2K6	-0.09	0.28	-10000	0	-0.69	65	65
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.067	0.23	-10000	0	-0.63	45	45
MITF	-0.078	0.25	-10000	0	-0.58	67	67
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	-0.02	0.084	-10000	0	-0.49	1	1
STAT3	-0.084	0.24	-10000	0	-0.78	31	31
STAT1	-0.01	0.022	-10000	0	-10000	0	0
CEBPD	-0.05	0.21	-10000	0	-0.66	21	21
PIK3CA	0.01	0.064	-10000	0	-0.82	3	3
PI3K	0.019	0.05	-10000	0	-0.62	3	3
JUN	-0.17	0.35	-10000	0	-0.82	113	113
PIAS3/MITF	-0.066	0.24	-10000	0	-0.6	55	55
MAPK11	-0.084	0.29	-10000	0	-0.78	55	55
STAT3 (dimer)/FOXO1	-0.001	0.2	-10000	0	-0.57	21	21
GRB2/SOS1/GAB family	-0.11	0.19	-10000	0	-0.67	32	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.11	0.25	-10000	0	-0.44	148	148
GRB2	0.014	0	-10000	0	-10000	0	0
JAK2	0.01	0.052	-10000	0	-0.82	2	2
LBP	-0.056	0.19	-10000	0	-0.63	11	11
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.014	0.004	-10000	0	-10000	0	0
MYC	-0.065	0.26	-10000	0	-0.95	23	23
FGG	-0.059	0.21	-10000	0	-0.67	23	23
macrophage differentiation	-0.071	0.23	-10000	0	-0.72	31	31
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.17	0.28	-10000	0	-0.56	148	148
JUNB	-0.056	0.23	-10000	0	-0.78	21	21
FOS	-0.2	0.36	-10000	0	-0.82	128	128
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.088	0.27	-10000	0	-0.48	125	125
STAT1/PIAS1	-0.072	0.23	-10000	0	-0.58	54	54
GRB2/SOS1/GAB family/SHP2/PI3K	0.039	0.06	-10000	0	-0.59	3	3
STAT3 (dimer)	-0.081	0.24	-10000	0	-0.76	31	31
PRKCD	-0.056	0.22	-10000	0	-0.63	38	38
IL6R	-0.014	0.15	-10000	0	-0.82	17	17
SOCS3	-0.095	0.35	-10000	0	-1	49	49
gp130 (dimer)/JAK1/JAK1/LMO4	-0.057	0.2	-10000	0	-0.54	72	72
Rac1/GTP	-0.094	0.23	-10000	0	-0.6	59	59
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	-0.087	0.21	-10000	0	-0.62	26	26
IRF1	-0.05	0.21	-10000	0	-0.64	25	25
mol:GDP	-0.089	0.25	-10000	0	-0.61	66	66
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.092	0.26	-10000	0	-0.62	66	66
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.095	0.29	-10000	0	-0.8	53	53
PTPN11	-0.01	0.058	-10000	0	-1.2	1	1
IL6/IL6RA	-0.13	0.27	-10000	0	-0.65	100	100
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	118	118
PIAS3	0.013	0	-10000	0	-10000	0	0
PTPRE	-0.089	0.15	-10000	0	-0.32	151	151
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	-0.092	0.26	-10000	0	-0.46	130	130
LMO4	0.013	0.009	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.099	0.23	0.38	1	-0.76	32	33
MCL1	0.059	0.048	-10000	0	-0.88	1	1

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.37	-9999	-1.3	40	40
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.032	0.11	-9999	-0.39	20	20
ATF2/c-Jun	-0.22	0.42	-9999	-0.96	116	116
MAPK11	-0.032	0.11	-9999	-0.39	20	20
MITF	-0.025	0.13	-9999	-0.41	40	40
MAPKAPK5	-0.025	0.13	-9999	-0.47	20	20
KRT8	-0.025	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	-0.025	0.13	-9999	-0.41	40	40
SLC9A1	-0.025	0.13	-9999	-0.41	40	40
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.07	0.19	-9999	-0.56	40	40
p38alpha-beta/MNK1	-0.021	0.13	-9999	-0.49	20	20
JUN	-0.21	0.42	-9999	-0.96	116	116
PPARGC1A	-0.23	0.25	-9999	-0.46	262	262
USF1	-0.025	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	-0.66	8	8
DDIT3	-0.027	0.13	-9999	-0.41	40	40
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.01	0.11	-9999	-0.39	19	19
p38alpha-beta/HBP1	-0.021	0.13	-9999	-0.49	20	20
CREB1	-0.045	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	-0.025	0.13	-9999	-0.41	40	40
PLA2G4A	-0.045	0.19	-9999	-0.59	45	45
GDI1	-0.025	0.13	-9999	-0.41	40	40
TP53	-0.033	0.16	-9999	-0.51	40	40
RPS6KA5	-0.074	0.2	-9999	-0.46	87	87
ESR1	-0.06	0.2	-9999	-0.55	53	53
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.026	0.13	-9999	-0.48	21	21
MEF2A	-0.026	0.13	-9999	-0.41	41	41
EIF4EBP1	-0.045	0.15	-9999	-0.46	40	40
KRT19	-0.1	0.2	-9999	-0.53	56	56
ELK4	-0.025	0.13	-9999	-0.47	20	20
ATF6	-0.025	0.13	-9999	-0.47	20	20
ATF1	-0.046	0.16	-9999	-0.47	41	41
p38alpha-beta/MAPKAPK2	-0.021	0.13	-9999	-0.49	20	20
p38alpha-beta/MAPKAPK3	-0.021	0.13	-9999	-0.49	20	20

×

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	0.082	-9999	-0.82	5	5
EGF/EGFR	-0.078	0.17	-9999	-0.45	83	83
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.072	0.16	-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	-0.085	0.2	-9999	-0.54	77	77
mol:GDP	-0.071	0.16	-9999	-0.45	77	77
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.003	0.086	-9999	-0.63	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	-0.43	77	77
FRAP1	-0.036	0.17	-9999	-0.44	77	77
EGF/EGFR dimer	-0.099	0.23	-9999	-0.63	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	-0.034	0.11	-10000	0	-0.31	70	70
GNB1/GNG2	-0.042	0.067	-10000	0	-0.2	44	44
AKT1	-0.006	0.1	-10000	0	-0.21	39	39
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	0.069	-10000	0	-0.71	1	1
RhoA/GTP	-0.029	0.045	-10000	0	-10000	0	0
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	-0.027	0.12	-10000	0	-0.55	12	12
G beta5/gamma2	-0.056	0.09	-10000	0	-0.27	45	45
PRKCH	-0.042	0.16	-10000	0	-0.36	72	72
DNM1	-0.014	0.15	-10000	0	-0.79	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	-0.82	20	20
G12 family/GTP	-0.072	0.11	-10000	0	-0.3	72	72
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	0.011	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	-0.82	138	138
mol:IP3	-0.049	0.18	-10000	0	-0.39	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	-0.095	0.2	-10000	0	-0.39	148	148
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	-0.82	5	5
PRKCB1	-0.049	0.17	-10000	0	-0.39	72	72
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.071	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	0.08	-10000	0	-0.35	17	17
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	-0.016	0.079	-10000	0	-1.1	1	1
MAPK14	-0.012	0.11	-10000	0	-0.23	44	44
TGM2/GTP	-0.061	0.2	-10000	0	-0.43	74	74
MAPK11	-0.012	0.11	-10000	0	-0.23	44	44
ARHGEF1	-0.01	0.088	-10000	0	-0.18	43	43
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	77	77
cAMP biosynthetic process	-0.049	0.16	-10000	0	-0.36	74	74
Gq family/GTP/EBP50	-0.045	0.12	-10000	0	-0.25	127	127
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.034	0.069	-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	-0.027	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	-0.64	5	5
PRKACA	0.002	0.095	-10000	0	-0.4	24	24
Gq family/GDP/G beta5/gamma2	-0.029	0.12	-10000	0	-0.36	27	27
TXA2/TP beta/beta Arrestin2	-0.022	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	-0.44	72	72
EGFR	0.005	0.082	-10000	0	-0.82	5	5
TXA2/TP alpha	-0.07	0.22	-10000	0	-0.49	73	73
Gq family/GTP	-0.078	0.13	-10000	0	-0.3	127	127
YES1	0.034	0.069	-10000	0	-0.71	1	1
GNAI2/GTP	-0.015	0.069	-10000	0	-0.9	1	1
PGD2/DP	-0.025	0.12	-10000	0	-0.64	20	20
SLC9A3R1	0.012	0.021	-10000	0	-0.31	2	2
FYN	0.034	0.069	-10000	0	-0.71	1	1
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.012	0.093	-10000	0	-0.33	38	38
PGK/cGMP	-0.15	0.24	-10000	0	-0.55	138	138
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.029	0.092	-10000	0	-0.61	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	-0.39	78	78
PRKCB	-0.051	0.17	-10000	0	-0.38	75	75
PRKCE	-0.044	0.17	-10000	0	-0.38	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	-0.061	0.21	-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	-0.048	0.18	-10000	0	-0.43	72	72
TP beta/GNAI2/GDP/G beta/gamma	-0.017	0.085	-10000	0	-1.3	1	1
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.35	-10000	0	-0.82	120	120
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	-0.82	10	10
Rac1/GTP	0.004	0.005	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.031	0.14	-9999	-0.45	39	39
NF kappa B1 p50/RelA/I kappa B alpha	-0.054	0.11	-9999	-0.54	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.064	0.15	-9999	-0.61	25	25
AP1	-0.26	0.35	-9999	-0.85	111	111
ILK	-0.031	0.15	-9999	-0.48	39	39
bone resorption	-0.047	0.15	-9999	-0.65	11	11
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.051	0.12	-9999	-0.44	39	39
ITGAV	0.01	0.052	-9999	-0.81	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.031	0.14	-9999	-0.63	25	25
alphaV/beta3 Integrin/Osteopontin	-0.068	0.15	-9999	-0.54	39	39
MAP3K1	-0.032	0.15	-9999	-0.49	39	39
JUN	-0.17	0.35	-9999	-0.82	113	113
MAPK3	-0.031	0.14	-9999	-0.45	39	39
MAPK1	-0.031	0.14	-9999	-0.45	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.82	1	1
MAPK8	-0.031	0.17	-9999	-0.5	46	46
ITGB3	-0.011	0.14	-9999	-0.81	15	15
NFKBIA	-0.025	0.14	-9999	-0.44	39	39
FOS	-0.2	0.36	-9999	-0.82	128	128
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.11	0.17	-9999	-0.7	4	4
NF kappa B1 p50/RelA	-0.06	0.11	-9999	-0.53	6	6
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	-0.47	44	44
MAP3K14	-0.039	0.15	-9999	-0.49	39	39
ROCK2	-0.028	0.18	-9999	-0.82	25	25
SPP1	-0.078	0.2	-9999	-0.42	105	105
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.045	0.13	-9999	-0.42	44	44
MMP2	-0.17	0.29	-9999	-0.66	102	102

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.088	0.22	-9999	-0.41	147	147
MAP3K8	-0.001	0.098	-9999	-0.82	7	7
FOS	-0.054	0.16	-9999	-0.5	35	35
PRKCA	-0.02	0.16	-9999	-0.82	19	19
PTPN7	-0.047	0.18	-9999	-0.47	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	-0.59	23	23
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	127	127
MAPK1	-0.029	0.12	-9999	-0.43	28	28
RAF1	-0.039	0.12	-9999	-0.57	23	23
KRAS	0.013	0.002	-9999	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.19	-9999	-0.46	69	69
IKBKB	-0.019	0.073	-9999	-0.33	4	4
AKT1	-0.043	0.1	-9999	-0.26	28	28
IKBKG	-0.018	0.077	-9999	-0.36	4	4
CALM1	-0.037	0.087	-9999	-0.35	3	3
PIK3CA	0.008	0.064	-9999	-0.82	3	3
MAP3K1	-0.078	0.18	-9999	-0.58	23	23
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.047	0.091	-9999	-0.38	3	3
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.081	0.13	-9999	-0.28	123	123
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	148	148
CD22	-0.15	0.23	-9999	-0.5	120	120
CAMK2G	-0.027	0.083	-9999	-0.32	3	3
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	25	25
SHC/GRB2/SOS1	-0.1	0.15	-9999	-10000	0	0
GO:0007205	-0.048	0.092	-9999	-0.38	3	3
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.038	0.088	-9999	-0.35	3	3
NFATC1	-0.073	0.16	-9999	-0.55	22	22
B-cell antigen/BCR complex	-0.17	0.24	-9999	-0.52	148	148
PAG1/CSK	-0.002	0.029	-9999	-0.63	1	1
NFKBIB	0.002	0.029	-9999	-0.11	3	3
HRAS	-0.04	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	-0.2	1	1
RasGAP/Csk	-0.14	0.2	-9999	-0.49	103	103
mol:GDP	-0.043	0.085	-9999	-0.35	3	3
PTEN	0.012	0.037	-9999	-0.82	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	-0.091	0.18	-9999	-0.43	82	82
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.053	0.09	-9999	-0.38	3	3
CSK	0.013	0.015	-9999	-0.31	1	1
FOS	-0.14	0.21	-9999	-0.47	131	131
CHUK	-0.018	0.077	-9999	-0.3	8	8
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	-0.48	112	112
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.035	-9999	-0.13	19	19
VAV2	-0.14	0.19	-9999	-0.43	105	105
ubiquitin-dependent protein catabolic process	0.007	0.028	-9999	-0.11	3	3
BTK	-0.018	0.16	-9999	-1.2	8	8
CD19	-0.15	0.2	-9999	-0.41	156	156
MAP4K1	-0.021	0.13	-9999	-0.4	42	42
CD72	0.011	0.029	-9999	-0.31	4	4
PAG1	0.012	0.037	-9999	-0.82	1	1
MAPK14	-0.059	0.16	-9999	-0.53	18	18
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.037	0.09	-9999	-0.32	3	3
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.066	0.17	-9999	-0.43	79	79
RAF1	-0.03	0.097	-9999	-0.32	4	4
RasGAP/p62DOK/SHIP	-0.14	0.2	-9999	-0.47	100	100
CD79A	-0.2	0.3	-9999	-0.52	195	195
re-entry into mitotic cell cycle	-0.08	0.13	-9999	-0.27	123	123
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.011	0.085	-9999	-10000	0	0
MAPK1	-0.011	0.085	-9999	-10000	0	0
CD72/SHP1	-0.1	0.21	-9999	-0.55	59	59
NFKB1	0.012	0.037	-9999	-0.82	1	1
MAPK8	-0.067	0.17	-9999	-0.55	26	26
actin cytoskeleton organization	-0.091	0.18	-9999	-0.38	86	86
NF-kappa-B/RelA	0.023	0.046	-9999	-0.2	1	1
Calcineurin	-0.037	0.06	-9999	-10000	0	0
PI3K	-0.13	0.17	-9999	-0.5	40	40
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.057	0.088	-9999	-0.34	3	3
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.11	0.24	-9999	-0.72	41	41
DAPP1	-0.14	0.26	-9999	-1.1	23	23
cytokine secretion	-0.067	0.15	-9999	-0.51	22	22
mol:DAG	-0.053	0.09	-9999	-0.38	3	3
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.02	0.092	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.17	0.24	-9999	-0.48	165	165
mol:PI-3-4-5-P3	-0.098	0.12	-9999	-0.35	38	38
ETS1	-0.018	0.078	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.17	-9999	-0.46	82	82
B-cell antigen/BCR complex/LYN	-0.13	0.21	-9999	-0.45	108	108
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.052	-9999	-0.82	2	2
RAC1	-0.097	0.19	-9999	-0.41	86	86
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.52	106	106
CARD11	-0.076	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	-0.033	0.18	-9999	-0.58	39	39
PDPK1	-0.045	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	-0.089	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.073	0.097	-10000	0	-10000	0	0
CRKL	-0.031	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	-0.82	3	3
HGF/MET/SHIP2	-0.14	0.2	-10000	0	-0.59	75	75
MAP3K5	-0.018	0.11	-10000	0	-0.47	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.19	-10000	0	-0.54	75	75
AP1	-0.27	0.42	-10000	0	-0.87	152	152
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	152	152
STAT3 (dimer)	-0.039	0.13	-10000	0	-0.39	25	25
GAB1/CRKL/SHP2/PI3K	-0.042	0.093	-10000	0	-0.59	3	3
INPP5D	-0.003	0.071	-10000	0	-0.31	25	25
CBL/CRK	-0.022	0.11	-10000	0	-0.3	25	25
PTPN11	0.012	0.037	-10000	0	-0.82	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.037	-10000	0	-0.82	1	1
ELK1	-0.048	0.062	-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	-0.5	2	3
HGF/MET/RANBP10	-0.14	0.2	-10000	0	-0.59	75	75
HRAS	-0.058	0.16	-10000	0	-0.42	75	75
DOCK1	-0.025	0.12	-10000	0	-0.34	29	29
GAB1	-0.041	0.12	-10000	0	-0.3	75	75
CRK	-0.031	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	75	75
JUN	-0.17	0.35	-10000	0	-0.82	113	113
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.07	0.1	-10000	0	-0.29	75	75
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.011	0.14	-10000	0	-0.65	2	2
GRB2/SHC	-0.038	0.096	-10000	0	-10000	0	0
FOS	-0.2	0.36	-10000	0	-0.82	128	128
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.048	0.062	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.14	0.21	-10000	0	-0.6	75	75
cell migration	-0.038	0.094	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.073	0.097	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.051	0.14	-10000	0	-0.36	75	75
MET/MUC20	-0.077	0.1	-10000	0	-0.21	182	182
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	75	75
RAF1	-0.047	0.15	-10000	0	-0.45	26	26
STAT3	-0.04	0.13	-10000	0	-0.39	25	25
cell proliferation	-0.047	0.18	-10000	0	-0.45	75	75
RPS6KB1	-0.015	0.039	-10000	0	-10000	0	0
MAPK3	-0.049	0.057	-10000	0	-10000	0	0
MAPK1	-0.049	0.057	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.008	0.13	-10000	0	-0.57	15	15
SRC	-0.039	0.13	-10000	0	-0.39	25	25
PI3K	-0.041	0.1	-10000	0	-0.32	28	28
MET/Glomulin	-0.058	0.093	-10000	0	-0.18	182	182
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.036	0.14	-10000	0	-0.42	26	26
MET	-0.1	0.16	-10000	0	-0.31	182	182
MAP4K1	-0.027	0.12	-10000	0	-0.33	34	34
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.036	0.14	-10000	0	-0.42	26	26
BAD	0.009	0.037	0.42	1	-0.5	2	3
MAP2K4	-0.009	0.1	-10000	0	-0.42	5	5
SHP2/GRB2/SOS1/GAB1	-0.057	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	-0.26	75	75
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	75	75
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	-0.33	25	25
PDPK1	-0.009	0.043	0.51	1	-0.57	2	3
HGF/MET/SHIP	-0.14	0.21	-10000	0	-0.57	83	83

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.026	0.079	0.29	38	-10000	0	38
RFC1	0.026	0.079	0.29	38	-10000	0	38
PRKDC	0.026	0.079	0.29	38	-10000	0	38
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	-0.019	0.16	-10000	0	-0.53	16	16
mol:ceramide	-0.021	0.15	-10000	0	-0.47	38	38
GSN	0.026	0.079	0.29	38	-10000	0	38
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	-0.029	0.078	0.32	3	-10000	0	3
MAP3K1	0.007	0.097	-10000	0	-10000	0	0
MAP3K7	0.011	0.005	-10000	0	-10000	0	0
RB1	0.024	0.079	0.29	37	-0.31	1	38
CFLAR	0.014	0.004	-10000	0	-10000	0	0
HGF/MET	-0.14	0.22	-10000	0	-0.61	78	78
ARHGDIB	0.023	0.081	0.29	38	-10000	0	38
FADD	0.011	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.026	0.078	-10000	0	-0.29	38	38
NFKB1	-0.049	0.09	-10000	0	-0.32	17	17
MAPK8	-0.051	0.21	-10000	0	-0.45	90	90
DFFA	0.026	0.079	0.29	38	-10000	0	38
DNA fragmentation during apoptosis	0.026	0.078	0.29	38	-10000	0	38
FAS/FADD/MET	-0.058	0.076	-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	0.026	0.079	0.29	38	-10000	0	38
DFFB	0.026	0.079	0.29	38	-10000	0	38
CHUK	-0.042	0.08	-10000	0	-0.73	1	1
FASLG	-0.063	0.23	-10000	0	-0.67	55	55
FAS/FADD	-0.001	0.001	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	75	75
LMNA	0.024	0.071	0.26	38	-10000	0	38
CASP6	0.026	0.079	0.29	38	-10000	0	38
CASP10	0.011	0.006	-10000	0	-10000	0	0
CASP3	0.031	0.095	0.35	41	-10000	0	41
PTPN13	0.003	0.09	-10000	0	-0.82	6	6
CASP8	0.008	0.045	0.45	3	-10000	0	3
IL6	-0.23	0.54	-10000	0	-1.4	89	89
MET	-0.1	0.16	-10000	0	-0.31	182	182
ICAD/CAD	0.024	0.073	0.27	38	-10000	0	38
FASLG/FAS/FADD/FAF1/Caspase 10	-0.022	0.15	-10000	0	-0.48	38	38
activation of caspase activity by cytochrome c	-0.029	0.077	0.32	3	-10000	0	3
PAK2	0.026	0.078	0.29	38	-10000	0	38
BCL2	-0.049	0.22	-10000	0	-0.82	38	38

×

TCGA08_p53

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
CDKN2A	-0.081	0.11	-9999	-0.21	207	207
TP53	-0.027	0.033	-9999	-10000	0	0
Senescence	-0.027	0.033	-9999	-10000	0	0
Apoptosis	-0.027	0.033	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.052	0.062	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

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	53	53
TBX21	-0.093	0.22	-10000	0	-0.62	38	38
IL12B	-0.008	0.1	-10000	0	-0.57	14	14
IL12A	-0.06	0.2	-10000	0	-0.61	56	56
IL6ST	-0.11	0.29	-10000	0	-0.82	72	72
IL27RA/JAK1	0.013	0.027	-10000	0	-10000	0	0
IL27	0.001	0.04	-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	-0.32	12	12
IL12RB1	-0.025	0.13	-10000	0	-0.38	48	48
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.091	0.21	-10000	0	-0.62	32	32
IL27/IL27R/JAK2/TYK2	-0.068	0.15	-10000	0	-0.47	20	20
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	17	-0.74	19	36
JAK2	0.011	0.053	-10000	0	-0.83	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	100	100
IL12/IL12R/TYK2/JAK2	-0.061	0.18	-10000	0	-0.76	16	16
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	0.049	-10000	0	-0.13	70	70
T cell differentiation	-0.006	0.008	-10000	0	-0.022	69	69
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)	-0.075	0.16	-10000	0	-0.52	25	25
STAT4	-0.024	0.14	-10000	0	-0.45	41	41
T cell activation	-0.012	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.063	0.18	-10000	0	-0.62	14	14
GATA3	-0.044	0.34	-10000	0	-1.5	26	26
IL18	-0.025	0.11	-10000	0	-0.29	60	60
positive regulation of mast cell cytokine production	-0.055	0.14	-10000	0	-0.51	11	11
IL27/EBI3	-0.1	0.12	-10000	0	-0.44	7	7
IL27RA	0.003	0.027	-10000	0	-10000	0	0
IL6	-0.15	0.32	-10000	0	-0.69	118	118
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	-0.64	33	33
EBI3	-0.15	0.17	-10000	0	-0.32	245	245
TNF	-0.067	0.21	-10000	0	-0.59	65	65

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.033	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	-0.013	0.2	-10000	0	-0.86	25	25
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.012	0.2	-10000	0	-0.87	25	25
mol:Ca2+	-0.1	0.23	-10000	0	-0.49	122	122
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.07	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	-0.41	23	23
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.035	0.13	-10000	0	-0.59	23	23
regulation of stress fiber formation	-0.012	0.12	0.36	25	-10000	0	25
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	0.012	0.12	-10000	0	-0.36	25	25
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	-0.82	1	1
GNAO1	-0.016	0.15	-10000	0	-0.7	21	21
HRAS	0.012	0.021	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.014	0.15	-10000	0	-0.58	25	25
E2/ER beta (dimer)	-0.004	0.049	-10000	0	-0.64	3	3
mol:GDP	-0.033	0.12	-10000	0	-0.56	25	25
mol:NADP	0.014	0.15	-10000	0	-0.58	25	25
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.11	0.24	-10000	0	-0.52	122	122
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.12	0.25	-10000	0	-0.53	122	122
PLCB2	-0.12	0.25	-10000	0	-0.54	121	121
IGF1	-0.18	0.35	-10000	0	-0.79	120	120
mol:L-citrulline	0.014	0.15	-10000	0	-0.58	25	25
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	-0.82	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	-0.058	0.18	-10000	0	-0.53	24	24
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	-0.035	0.13	-10000	0	-0.59	23	23
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.043	0.14	-10000	0	-0.64	23	23
STRN	-0.04	0.2	-10000	0	-0.82	32	32
GNAL	-0.094	0.28	-10000	0	-0.82	65	65
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.017	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	-0.82	1	1
HBEGF	-0.004	0.16	-10000	0	-0.5	32	32
cAMP biosynthetic process	-0.089	0.18	-10000	0	-0.48	86	86
SRC	0.015	0.14	-10000	0	-0.5	24	24
PI3K	-0.004	0.048	-10000	0	-0.63	3	3
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.029	0.11	-10000	0	-0.5	25	25
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.099	0.18	-10000	0	-0.52	38	38
Gs family/GTP	-0.091	0.19	-10000	0	-0.49	86	86
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	0.015	0.14	-10000	0	-0.55	25	25
mol:DAG	-0.11	0.24	-10000	0	-0.52	122	122
Gs family/GDP/Gbeta gamma	-0.072	0.16	-10000	0	-0.4	86	86
MSN	0.011	0.12	-10000	0	-0.38	25	25
Gq family/GTP	-0.15	0.24	-10000	0	-0.56	127	127
mol:PI-3-4-5-P3	-0.01	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	-0.015	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	-0.82	10	10
MAPKKK cascade	-0.007	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	0.012	0.12	-10000	0	-0.36	25	25
ROCK2	0.001	0.14	-10000	0	-0.4	47	47
GNA14	-0.18	0.35	-10000	0	-0.82	120	120
GNA15	-0.012	0.093	-10000	0	-0.33	38	38
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.027	0.19	-10000	0	-0.48	63	63
MMP2	0.016	0.14	-10000	0	-0.49	28	28

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.12	0.1	-9999	-0.65	7	7
EPHB2	0.008	0.064	-9999	-0.82	3	3
Syndecan-2/TACI	-0.13	0.26	-9999	-0.56	130	130
LAMA1	-0.049	0.22	-9999	-0.8	38	38
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	-0.55	7	7
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.023	0.1	-9999	-0.75	2	2
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	-0.57	33	33
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	-0.82	3	3
Syndecan-2/MMP2	0.009	0.099	-9999	-0.58	13	13
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.079	0.098	-9999	-10000	0	0
dendrite morphogenesis	0.014	0.079	-9999	-0.54	10	10
Syndecan-2/GM-CSF	-0.11	0.098	-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	-0.087	0.091	-9999	-0.51	7	7
MAPK1	-0.087	0.091	-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	195	195
MAPK8	0.016	0.11	-9999	-0.55	18	18
Syndecan-2/alpha2/beta1 Integrin	-0.086	0.14	-9999	-0.51	41	41
Syndecan-2/Kininogen	-0.007	0.077	-9999	-0.55	7	7
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.032	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	-0.54	7	7
actin cytoskeleton reorganization	-0.12	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	133	133
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.079	0.098	-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	-0.49	7	7
FN1	-0.22	0.15	-9999	-0.31	364	364
Syndecan-2/IL8	-0.039	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	340	340
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	0.057	-9999	-0.49	7	7
PRKACA	0.027	0.061	-9999	-0.49	7	7
angiogenesis	-0.039	0.12	-9999	-0.54	18	18
MMP2	-0.001	0.1	-9999	-0.63	11	11
IL8	-0.083	0.18	-9999	-0.36	131	131
calcineurin-NFAT signaling pathway	-0.13	0.25	-9999	-0.55	130	130

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.006	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	291	291
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	-0.82	138	138
DUSP8	0.003	0.082	-9999	-0.52	10	10
PGK/cGMP/p38 alpha	-0.16	0.2	-9999	-0.46	141	141
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	-0.82	81	81
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1/OSM/MEKK3/MKK3	-0.001	0.008	-9999	-10000	0	0
TRAF6	0.01	0.052	-9999	-0.82	2	2
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.012	0.021	-9999	-0.31	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.062	0.13	-9999	-0.36	17	17
BLK	-0.25	0.37	-9999	-0.75	171	171
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	-0.51	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	-0.06	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	-0.45	6	6
p38alpha-beta/MKP5	-0.052	0.13	-9999	-0.48	7	7
PGK/cGMP	-0.18	0.28	-9999	-0.64	138	138
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.12	0.2	-9999	-0.48	81	81
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.47	0.41	-9999	-0.82	291	291

×

Regulation of Androgen receptor activity

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
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	-0.033	0.15	-9999	-0.65	16	16
JUN	-0.18	0.34	-9999	-0.82	113	113
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	-0.69	17	17
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	0.059	-9999	-10000	0	0
NCOA2	-0.073	0.24	-9999	-0.82	48	48
CEBPA	0.006	0.083	-9999	-0.82	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	108	108
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	-0.41	78	78
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	0.096	-9999	-0.64	11	11
T-DHT/AR/TIF2/CARM1	-0.13	0.24	-9999	-0.7	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	146	146
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.055	0.15	-9999	-0.68	19	19
TMPRSS2	-0.057	0.31	-9999	-1.2	32	32
RXRG	-0.28	0.12	-9999	-0.32	444	444
mol:9cRA	-0.002	0.002	-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	-0.82	11	11
KLK2	-0.48	0.42	-9999	-0.83	295	295
AR	-0.15	0.22	-9999	-0.38	211	211
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	-0.33	11	11
T-DHT/AR/RACK1/Src	-0.079	0.15	-9999	-0.67	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	-0.056	0.16	-9999	-0.46	50	50
T-DHT/AR/Hsp90	-0.058	0.15	-9999	-0.68	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	-0.82	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

×

RXR and RAR heterodimerization with other nuclear receptor

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
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	-0.059	0.11	-9999	-0.35	49	49
RXRs/LXRs/DNA/Oxysterols	-0.048	0.15	-9999	-0.46	58	58
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.021	0.083	-9999	-0.34	24	24
RXRs/NUR77	-0.26	0.25	-9999	-0.63	150	150
RXRs/PPAR	-0.055	0.064	-9999	-0.4	11	11
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.013	0.079	-9999	-0.48	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	0.054	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	0.01	-9999	-10000	0	0
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	-0.098	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	-0.11	0.067	-9999	-0.52	4	4
NR4A1	-0.23	0.38	-9999	-0.81	148	148
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.048	0.048	-9999	-0.32	4	4
RXRG	-0.28	0.12	-9999	-0.32	444	444
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	-0.82	11	11
PPARG	-0.001	0.1	-9999	-0.61	12	12
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.41	-9999	-1.3	58	58
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.047	0.15	-9999	-0.46	58	58
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.14	-9999	-0.82	14	14
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.45	175	175
SREBF1	-0.037	0.14	-9999	-0.62	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.082	-9999	-0.58	4	4
ABCA1	-0.037	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	-0.05	0.22	-9999	-0.82	38	38

×

Visual signal transduction: Rods

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
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	-0.065	0.24	-9999	-0.81	48	48
CNG Channel	-0.03	0.086	-9999	-0.5	10	10
mol:Na +	-0.025	0.083	-9999	-0.53	4	4
mol:ADP	-0.065	0.24	-9999	-0.8	48	48
RGS9-1/Gbeta5/R9AP	-0.088	0.2	-9999	-0.55	79	79
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.025	0.085	-9999	-0.55	4	4
CNGB1	-0.004	0.071	-9999	-0.31	25	25
RDH5	-0.2	0.16	-9999	-0.31	322	322
SAG	0.002	0.015	-9999	-0.31	1	1
mol:Ca2+	0.013	0.09	-9999	-0.8	1	1
Na + (4 Units)	-0.023	0.076	-9999	-0.76	1	1
RGS9	-0.073	0.25	-9999	-0.79	54	54
GNB1/GNGT1	-0.003	0.024	-9999	-10000	0	0
GNAT1/GDP	-0.077	0.18	-9999	-0.48	79	79
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	0.16	-9999	-0.31	322	322
mol:cGMP	-0.016	0.07	-9999	-0.48	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.13	0.099	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0	0.097	-9999	-0.56	12	12
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	-0.036	0.2	-9999	-0.82	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	-0.088	0.2	-9999	-0.55	79	79
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.022	-9999	-0.3	1	1
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	82	82
GUCA1A	0.004	0.033	-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

×

Integrins in angiogenesis

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
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	0.016	0.15	-9999	-0.52	19	19
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.026	0.11	-9999	-0.31	60	60
SRC	0.013	0.015	-9999	-0.31	1	1
CDKN1B	-0.062	0.18	-9999	-0.61	45	45
VEGFA	0.008	0.064	-9999	-0.82	3	3
ILK	-0.062	0.18	-9999	-0.61	45	45
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.057	0.16	-9999	-0.57	45	45
PTK2B	0.018	0.11	-9999	-0.5	22	22
alphaV/beta3 Integrin/JAM-A	-0.058	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	-0.019	0.1	-9999	-0.58	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.26	-9999	-0.53	160	160
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.004	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	170	170
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.82	3	3
alphaV/beta3 Integrin/Osteopontin	-0.069	0.16	-9999	-0.56	39	39
RPS6KB1	-0.2	0.24	-9999	-0.57	119	119
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.094	0.15	-9999	-0.72	17	17
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.094	0.15	-9999	-0.72	17	17
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	0.006	0.026	-9999	-10000	0	0
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	-0.82	3	3
ITGB3	-0.011	0.14	-9999	-0.82	15	15
IGF1	-0.18	0.35	-9999	-0.79	120	120
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	-0.82	8	8
PIK3C2A	-0.063	0.18	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.053	0.14	-9999	-0.77	3	3
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.023	0.11	-9999	-0.53	22	22
FAK1/Vinculin	0.024	0.12	-9999	-0.42	16	16
alphaV beta3/Integrin/ppsTEM5	-0.018	0.1	-9999	-0.57	16	16
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.066	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	-0.021	0.11	-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	0.15	-9999	-0.31	364	364
alphaV/beta3 Integrin/Pyk2	-0.022	0.11	-9999	-0.5	22	22
SDC1	0.01	0.033	-9999	-0.31	5	5
VAV3	0.026	0.097	-9999	-0.52	14	14
PTPN11	0.012	0.037	-9999	-0.82	1	1
IRS1	-0.084	0.27	-9999	-0.82	59	59
FAK1/Paxillin	0.024	0.12	-9999	-0.48	8	8
cell migration	0.034	0.12	-9999	-0.43	8	8
ITGAV	0.01	0.052	-9999	-0.82	2	2
PI3K	-0.054	0.15	-9999	-0.44	61	61
SPP1	-0.078	0.2	-9999	-0.42	105	105
KDR	0.007	0.074	-9999	-0.82	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.052	-9999	-0.82	2	2
COL4A3	-0.011	0.14	-9999	-0.82	15	15
angiogenesis	-0.082	0.18	-9999	-0.59	37	37
Rac1/GTP	-0.013	0.082	-9999	-0.47	14	14
EDIL3	-0.025	0.14	-9999	-0.43	43	43
cell proliferation	-0.021	0.11	-9999	-0.59	18	18

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.38	21	21
NFATC4	0.001	0.11	-9999	-0.5	3	3
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.044	0.13	-9999	-0.4	54	54
JUN	0.004	0.097	-9999	-0.27	13	13
HRAS	0.012	0.021	-9999	-0.32	2	2
DOCK7	-0.012	0.14	-9999	-0.38	57	57
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.053	0.15	-9999	-0.49	54	54
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.022	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	0.12	-9999	-0.4	21	21
ErbB2/ErbB3/neuregulin 2	-0.067	0.17	-9999	-0.51	65	65
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.023	0.081	-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	117	117
FOS	-0.1	0.28	-9999	-0.51	152	152
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.044	0.13	-9999	-0.4	54	54
MAPK3	-0.079	0.26	-9999	-0.5	114	114
MAPK1	-0.079	0.26	-9999	-0.5	114	114
JAK2	-0.011	0.13	-9999	-0.38	56	56
NF2	-0.002	0.005	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.014	0.13	-9999	-0.37	54	54
NRG1	-0.064	0.24	-9999	-0.8	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	-0.74	12	12
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.003	0.01	-9999	-10000	0	0
STAT3 (dimer)	0	0.003	-9999	-10000	0	0
RNF41	0.027	0.007	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.031	0.085	-9999	-0.38	2	2
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.052	0.2	-9999	-0.44	45	45
myelination	0.01	0.11	-9999	-0.46	3	3
PPP3CB	-0.008	0.12	-9999	-0.35	54	54
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-9999	-0.65	2	2
NRG2	-0.08	0.26	-9999	-0.79	58	58
mol:GDP	-0.013	0.13	-9999	-0.37	54	54
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.003	0.13	-9999	-0.41	21	21
SRC	0.013	0.015	-9999	-0.31	1	1
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.011	0.13	-9999	-0.38	55	55
MAP2K1	-0.071	0.23	-9999	-0.61	27	27
heart morphogenesis	-0.044	0.13	-9999	-0.4	54	54
RAS family/GDP	-0.005	0.11	-9999	-0.64	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

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.012	0.22	-10000	0	-0.97	21	21
NCK1/PAK1/Dok-R	-0.028	0.09	-10000	0	-0.43	22	22
NCK1/Dok-R	-0.067	0.24	-10000	0	-1.2	21	21
PIK3CA	0.008	0.064	-10000	0	-0.82	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	-0.011	0.069	0.26	3	-0.33	12	15
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.059	0.23	-10000	0	-1.1	21	21
FN1	-0.22	0.15	-10000	0	-0.31	364	364
PLD2	0.001	0.28	-10000	0	-1.3	21	21
PTPN11	0.012	0.037	-10000	0	-0.82	1	1
GRB14	-0.012	0.14	-10000	0	-0.82	15	15
ELK1	0.017	0.24	-10000	0	-1.1	21	21
GRB7	-0.041	0.12	-10000	0	-0.31	84	84
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.1	0.24	-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	-0.067	0.24	-10000	0	-1.2	21	21
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.028	0.17	-10000	0	-0.69	21	21
PLG	-0.008	0.28	-10000	0	-1.3	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.011	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	-0.86	15	15
BMX	-0.013	0.29	-10000	0	-1.2	23	23
ANGPT1	-0.036	0.29	-10000	0	-1.5	18	18
tube development	-0.016	0.18	-10000	0	-0.73	21	21
ANGPT4	-0.062	0.23	-10000	0	-0.75	50	50
response to hypoxia	0	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.018	0.3	-10000	0	-1.3	22	22
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.018	0.21	-10000	0	-0.84	21	21
mol:L-citrulline	0.028	0.17	-10000	0	-0.69	21	21
AGTR1	-0.32	0.41	-10000	0	-0.81	203	203
MAPK14	-0.01	0.27	-10000	0	-1.2	21	21
Tie2/SHP2	-0.027	0.16	-10000	0	-1.4	6	6
TEK	0.015	0.18	-10000	0	-1.5	6	6
RPS6KB1	0.012	0.21	-10000	0	-0.93	21	21
Angiotensin II/AT1	-0.25	0.32	-10000	0	-0.63	203	203
Tie2/Ang1/GRB2	-0.004	0.29	-10000	0	-1.3	21	21
MAPK3	0.012	0.25	-10000	0	-1.1	21	21
MAPK1	0.012	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	-0.82	1	1
MAPK8	-0.007	0.29	-10000	0	-1.2	24	24
PI3K	-0.003	0.25	-10000	0	-1.1	21	21
FES	-0.01	0.27	-10000	0	-1.2	21	21
Crk/Dok-R	-0.067	0.24	-10000	0	-1.2	21	21
Tie2/Ang1/ABIN2	-0.004	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	0.012	0.21	-10000	0	-0.93	21	21
Tie2/Ang2	-0.038	0.24	-10000	0	-1	21	21
Tie2/Ang1	-0.011	0.31	-10000	0	-1.4	21	21
FOXO1	0.023	0.2	-10000	0	-0.86	21	21
ELF1	0.015	0.077	-10000	0	-0.84	4	4
ELF2	-0.002	0.27	-10000	0	-1.2	21	21
mol:Choline	0.004	0.26	-10000	0	-1.2	21	21
cell migration	-0.024	0.055	-10000	0	-0.24	21	21
FYN	-0.022	0.21	-10000	0	-0.85	21	21
DOK2	-0.001	0.079	-10000	0	-0.82	2	2
negative regulation of cell cycle	-0.006	0.16	-10000	0	-0.58	21	21
ETS1	0.016	0.044	-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	-0.086	0.27	-10000	0	-0.76	66	66
MAPKKK cascade	0.004	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	0.004	0.26	-10000	0	-1.2	21	21
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.028	0.17	-10000	0	-0.69	21	21
Rac1/GTP	-0.05	0.17	-10000	0	-0.86	21	21
MMP2	-0.006	0.28	-10000	0	-1.3	22	22

×

Signaling events mediated by PRL

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
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0.002	0.097	-9999	-0.82	7	7
CDKN1A	-0.013	0.088	-9999	-0.26	2	2
PRL-3/alpha Tubulin	-0.018	0.057	-9999	-10000	0	0
mol:Ca2+	-0.014	0.11	-9999	-0.38	28	28
AGT	-0.022	0.14	-9999	-0.46	37	37
CCNA2	-0.063	0.2	-9999	-0.45	108	108
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.11	0.27	-9999	-0.62	108	108
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	108	108
PTP4A3	-0.015	0.093	-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	-0.31	1	1
RAC1	-0.017	0.093	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.068	0.2	-9999	-0.45	108	108
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.013	0.042	-9999	-10000	0	0
RHOC	-0.017	0.093	-9999	-10000	0	0
RHOA	-0.017	0.093	-9999	-10000	0	0
cell motility	-0.016	0.099	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.062	0.2	-9999	-0.44	108	108
PRL-3/alpha1 Integrin	-0.026	0.095	-9999	-0.67	7	7
ROCK1	-0.016	0.1	-9999	-10000	0	0
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.072	0.21	-9999	-0.48	108	108
ATF5	0	0.064	-9999	-0.31	20	20

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.4	42	42
MAP3K8	0.002	0.097	-9999	-0.82	7	7
PRKCB	-0.022	0.12	-9999	-0.37	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	124	124
MAP3K7	0.012	0.11	-9999	-0.55	6	6
GRAP2	-0.045	0.21	-9999	-0.82	33	33
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.019	0.11	-9999	-0.52	7	7
LAT	0.005	0.077	-9999	-0.82	4	4
LCP2	0.008	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	0.004	0.12	-9999	-0.59	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.053	0.15	-9999	-0.52	41	41

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-10000	0	-0.82	1	1
Jak2/Leptin Receptor	-0.025	0.096	-10000	0	-0.43	13	13
PTP1B/AKT1	-0.004	0.064	-10000	0	-0.34	2	2
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.013	0.07	-10000	0	-0.34	4	4
EGFR	0.003	0.083	-10000	0	-0.82	5	5
EGF/EGFR	-0.085	0.18	-10000	0	-0.5	77	77
CSF1	0	0.1	-10000	0	-0.82	8	8
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.014	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.099	0.12	-10000	0	-0.44	20	20
Insulin Receptor/Insulin	-0.016	0.054	-10000	0	-0.48	3	3
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	-0.34	3	3
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	-0.37	7	7
TXN	0.011	0.015	-10000	0	-0.32	1	1
PTP1B/IRS1/GRB2	-0.055	0.17	-10000	0	-0.49	60	60
cell migration	0.013	0.07	0.34	4	-10000	0	4
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.043	0.19	-10000	0	-0.59	47	47
ITGA2B	-0.075	0.26	-10000	0	-0.82	53	53
CSF1R	0.008	0.049	-10000	0	-0.4	6	6
Prolactin Receptor/Prolactin	-0.039	0.15	-10000	0	-0.64	26	26
FGR	0.011	0.029	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.005	0.066	-10000	0	-0.36	2	2
Crk/p130 Cas	0	0.061	-10000	0	-0.34	2	2
DOK1	0.005	0.063	-10000	0	-0.36	1	1
JAK2	-0.013	0.091	-10000	0	-0.4	14	14
Jak2/Leptin Receptor/Leptin	-0.05	0.13	-10000	0	-0.57	24	24
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.013	0.07	-10000	0	-0.34	4	4
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.19	0.19	-10000	0	-0.34	284	284
SRC	0.011	0.03	-10000	0	-10000	0	0
ITGB3	-0.013	0.14	-10000	0	-0.82	15	15
CAT1/PTP1B	-0.091	0.15	-10000	0	-0.39	55	55
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.013	0.015	-10000	0	-0.31	1	1
PI3K	-0.017	0.061	-10000	0	-0.5	6	6
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.046	0.13	-10000	0	-0.6	24	24
negative regulation of transcription	-0.012	0.091	-10000	0	-0.39	14	14
FCGR2A	-0.007	0.085	-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	-0.25	0.37	-10000	0	-0.75	171	171
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	-0.49	53	53
PRL	0.001	0.015	-10000	0	-0.31	1	1
SOCS3	-0.055	0.32	-10000	0	-1.5	23	23
SPRY2	0.009	0.055	-10000	0	-0.65	3	3
Insulin Receptor/Insulin/IRS1	-0.068	0.18	-10000	0	-0.55	62	62
CSF1/CSF1R	-0.009	0.094	-10000	0	-0.51	10	10
Ras protein signal transduction	0.021	0.023	-10000	0	-10000	0	0
IRS1	-0.084	0.27	-10000	0	-0.82	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	-0.008	0.071	-10000	0	-0.31	6	6
STAT5A	-0.008	0.071	-10000	0	-0.31	6	6
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.069	-10000	0	-0.39	3	3
CSN2	-0.006	0.054	-10000	0	-10000	0	0
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
LAT	0.001	0.065	-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	219	219

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.6	1	1
AP1	-0.25	0.36	-9999	-0.68	177	177
mol:PIP3	-0.04	0.12	-9999	-0.64	8	8
AKT1	-0.025	0.095	-9999	-0.58	5	5
PTK2B	0.001	0.084	-9999	-0.33	13	13
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	-0.32	1	1
MAGI3	0.012	0.037	-9999	-0.82	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.013	0.13	-9999	-0.44	39	39
HRAS/GDP	-0.001	0.013	-9999	-0.21	2	2
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	-0.026	0.2	-9999	-0.64	41	41
ADCY4	-0.013	0.19	-9999	-0.61	40	40
ADCY5	-0.044	0.21	-9999	-0.64	43	43
ADCY6	-0.013	0.19	-9999	-0.61	40	40
ADCY7	-0.013	0.19	-9999	-0.61	40	40
ADCY1	-0.016	0.19	-9999	-0.62	40	40
ADCY2	-0.036	0.21	-9999	-0.66	41	41
ADCY3	-0.013	0.19	-9999	-0.61	40	40
ADCY8	-0.055	0.19	-9999	-0.65	40	40
ADCY9	-0.013	0.19	-9999	-0.61	40	40
GSK3B	0.009	0.081	-9999	-0.33	5	5
arachidonic acid secretion	-0.006	0.18	-9999	-0.57	39	39
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	0.078	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.036	0.11	-9999	-0.97	6	6
JUN	-0.17	0.35	-9999	-0.82	113	113
LPA/LPA2/NHERF2	-0.001	0.007	-9999	-10000	0	0
TIAM1	-0.046	0.13	-9999	-1.2	6	6
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.003	0.075	-9999	-0.32	1	1
PLCB3	0.03	0.009	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
positive regulation of mitosis	-0.006	0.18	-9999	-0.57	39	39
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	-0.019	0.17	-9999	-0.57	41	41
EGFR/PI3K-beta/Gab1	-0.042	0.13	-9999	-0.68	8	8
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	0.001	0.15	-9999	-0.49	39	39
GNAI2	-0.019	0.17	-9999	-0.57	41	41
GNAI3	-0.019	0.17	-9999	-0.57	41	41
GNAI1	-0.02	0.17	-9999	-0.58	40	40
LPA/LPA3	-0.01	0.044	-9999	-10000	0	0
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.055	0.18	-9999	-0.65	41	41
HB-EGF/EGFR	-0.056	0.17	-9999	-0.53	51	51
HBEGF	-0.062	0.19	-9999	-0.62	46	46
mol:DAG	0.003	0.075	-9999	-0.32	1	1
cAMP biosynthetic process	-0.026	0.19	-9999	-0.56	53	53
NFKB1	0.012	0.037	-9999	-0.82	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.01	0.078	-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	-10000	0	0
LPAR1	-0.049	0.23	-9999	-0.83	39	39
IL8	-0.13	0.2	-9999	-0.48	57	57
PTK2	-0.009	0.15	-9999	-0.5	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.013	0.13	-9999	-0.45	39	39
EGFR	0.005	0.082	-9999	-0.82	5	5
PLCG1	-0.017	0.086	-9999	-0.31	10	10
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	-0.71	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	-0.37	33	33
HRAS/GTP	-0.008	0.19	-9999	-0.59	39	39
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.085	0.24	-9999	-0.58	83	83
PRKCE	0.006	0.083	-9999	-0.82	5	5
PRKCD	0.01	0.072	-9999	-10000	0	0
Gi(beta/gamma)	-0.007	0.18	-9999	-0.59	39	39
mol:LPA	0.003	0.018	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.028	0.13	-9999	-0.64	7	7
MAPKKK cascade	-0.006	0.18	-9999	-0.57	39	39
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	120	120
GNA15	0.009	0.055	-9999	-0.43	1	1
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.009	0.089	-9999	-0.43	5	5
GNA11	0.01	0.069	-9999	-0.42	10	10
Rac1/GTP	-0.037	0.11	-9999	-1	6	6
MMP2	-0.027	0.2	-9999	-0.64	41	41

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.032	0.043	-9999	-0.92	1	1
VEGFR1 homodimer/NRP1	-0.002	0.041	-9999	-0.93	1	1
mol:DAG	-0.012	0.16	-9999	-0.49	52	52
VEGFR1 homodimer/NRP1/VEGFR 121	-0.005	0.066	-9999	-0.77	3	3
CaM/Ca2+	-0.005	0.15	-9999	-0.45	52	52
HIF1A	0.021	0.018	-9999	-0.38	1	1
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.009	0.16	-9999	-1.1	2	2
PLCG1	-0.013	0.16	-9999	-0.49	52	52
NOS3	0.016	0.15	-9999	-0.43	52	52
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.017	0.15	-9999	-0.41	52	52
FLT1	0.031	0.047	-9999	-1	1	1
PGF	-0.071	0.25	-9999	-0.82	51	51
VEGFR1 homodimer/NRP2/VEGFR121	-0.015	0.074	-9999	-0.76	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.82	3	3
eNOS/Hsp90	0.024	0.14	-9999	-0.8	1	1
endothelial cell proliferation	-0.024	0.19	-9999	-0.51	53	53
mol:Ca2+	-0.012	0.16	-9999	-0.48	52	52
MAPK3	-0.012	0.17	-9999	-0.43	69	69
MAPK1	-0.012	0.17	-9999	-0.43	69	69
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.071	0.25	-9999	-0.82	51	51
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.008	0.13	-9999	-0.82	13	13
VEGFA homodimer	0.008	0.064	-9999	-0.82	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	-0.95	2	2
PI3K	-0.05	0.15	-9999	-0.46	54	54
PRKCA	-0.021	0.18	-9999	-0.46	69	69
PRKCB	-0.02	0.17	-9999	-0.47	56	56
VEGFR1 homodimer/PLGF homodimer	-0.026	0.18	-9999	-0.54	52	52
VEGFA	0.008	0.064	-9999	-0.82	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.012	0.16	-9999	-0.49	52	52
RASA1	0.041	0.04	-9999	-0.85	1	1
NRP2	-0.014	0.091	-9999	-10000	0	0
VEGFR1 homodimer	0.031	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	-0.8	4	4
PTPN11	0.012	0.037	-9999	-0.82	1	1
mol:PI-3-4-5-P3	-0.05	0.15	-9999	-0.46	54	54
mol:L-citrulline	0.017	0.15	-9999	-0.41	52	52
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	54	54
PDPK1	0	0.16	-9999	-0.44	54	54
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.005	0.082	-9999	-0.89	3	3
mol:NADP	0.017	0.15	-9999	-0.41	52	52
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	0.017	0.066	-9999	-0.92	1	1

×

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	-0.82	4	4
SMAD3/SMAD4/ER alpha	-0.051	0.14	-10000	0	-0.59	23	23
AKT1	0.008	0.011	-10000	0	-10000	0	0
GSC	-0.19	0.54	-10000	0	-1.5	68	68
NKX2-5	0.002	0.028	-10000	0	-0.31	4	4
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	0.059	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.077	-10000	0	-0.54	5	5
SMAD3/SMAD4/VDR	0.009	0.044	-10000	0	-10000	0	0
MYC	0.001	0.14	-10000	0	-0.82	13	13
CDKN2B	-0.076	0.14	-10000	0	-10000	0	0
AP1	-0.25	0.5	-10000	0	-0.98	144	144
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.055	-10000	0	-0.71	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.062	-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	-0.032	0.18	-10000	0	-0.77	28	28
SKI/SIN3/HDAC complex/NCoR1	0.041	0.029	-10000	0	-10000	0	0
MEF2C/TIF2	-0.04	0.17	-10000	0	-0.54	34	34
endothelial cell migration	-0.006	0.1	1.4	1	-10000	0	1
MAX	0.013	0.007	-10000	0	-10000	0	0
RBBP7	0.012	0.004	-10000	0	-10000	0	0
RBBP4	0.007	0.064	-10000	0	-0.82	3	3
RUNX2	-0.073	0.15	-10000	0	-0.32	130	130
RUNX3	-0.012	0.13	-10000	0	-0.62	20	20
RUNX1	-0.13	0.16	-10000	0	-0.31	219	219
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.007	-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	0.015	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.035	0.093	-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	0.005	0.11	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.042	0.13	-10000	0	-0.59	22	22
SMAD3/SMAD4/ATF3	-0.16	0.27	-10000	0	-0.62	119	119
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	-1	134	134
SMAD3/SMAD4/IRF7	-0.017	0.046	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.005	0.1	-10000	0	-1.2	1	1
mesenchymal cell differentiation	0.064	0.095	0.5	3	-10000	0	3
DLX1	-0.03	0.18	-10000	0	-0.82	26	26
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.22	0.39	-10000	0	-0.88	128	128
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	0.012	-10000	0	-10000	0	0
LAMC1	0.025	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.017	0.045	-10000	0	-10000	0	0
IRF7	0.014	0.015	-10000	0	-0.31	1	1
ESR1	-0.046	0.19	-10000	0	-0.53	55	55
HNF4A	-0.003	0.045	-10000	0	-0.31	10	10
MEF2C	0.006	0.097	-10000	0	-1	1	1
SMAD2-3/SMAD4	-0.031	0.055	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.024	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.017	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	-0.82	1	1
HDAC1	0.012	0.004	-10000	0	-10000	0	0
HDAC2	0.012	0.004	-10000	0	-10000	0	0
SNIP1	0.008	0.052	-10000	0	-0.82	2	2
GCN5L2	0.005	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.012	0.046	-10000	0	-10000	0	0
MSG1/HSC70	-0.18	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	-0.41	7	7
SMAD2/SMAD2/SMAD4	0.014	0.028	-10000	0	-10000	0	0
NCOR1	0.012	0.004	-10000	0	-10000	0	0
NCOA2	-0.066	0.24	-10000	0	-0.82	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	-0.005	0.098	-10000	0	-1	1	1
CITED1	-0.26	0.14	-10000	0	-0.32	413	413
SMAD2-3/SMAD4/ARC105	-0.022	0.046	-10000	0	-10000	0	0
RBL1	-0.007	0.13	-10000	0	-0.82	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.006	0.081	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.084	0.11	-10000	0	-0.49	18	18
SMAD7	-0.1	0.28	-10000	0	-0.6	93	93
MYC/MIZ-1	0.014	0.11	-10000	0	-0.63	13	13
SMAD3/SMAD4	0.06	0.1	0.31	39	-0.35	1	40
IL10	-0.028	0.19	-10000	0	-0.61	40	40
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	-0.017	0.14	-10000	0	-0.5	26	26
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	126	126
SMAD3/SMAD4/SP1	-0.016	0.055	-10000	0	-10000	0	0
FOXG1	-0.001	0.062	-10000	0	-0.35	13	13
FOXO3	0.017	0.015	-10000	0	-10000	0	0
FOXO1	0.017	0.015	-10000	0	-10000	0	0
FOXO4	0.017	0.015	-10000	0	-10000	0	0
heart looping	0.006	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	-0.6	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	-0.54	31	31
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.037	-10000	0	-0.82	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.077	0.11	-10000	0	-0.53	15	15
SMAD3/SMAD4/SP1-3	0.007	0.058	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.015	0.022	-10000	0	-10000	0	0
SIN3B	0.012	0.004	-10000	0	-10000	0	0
SIN3A	0.012	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.013	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	210	210
AR	-0.34	0.41	-10000	0	-0.82	210	210
negative regulation of cell growth	-0.04	0.13	-10000	0	-0.55	4	4
SMAD3/SMAD4/MYOD	-0.023	0.05	-10000	0	-10000	0	0
E2F5	0.012	0.037	-10000	0	-0.82	1	1
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.01	0.066	-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	-0.82	1	1
SMAD3/SMAD4/AP1	-0.26	0.51	-10000	0	-1	134	134
SMAD3/SMAD4/RUNX2	-0.065	0.095	-10000	0	-0.5	3	3
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	-0.82	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	0.052	-9999	-0.82	2	2
Aurora C/Aurora B/INCENP	-0.04	0.077	-9999	-0.64	2	2
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	114	114
AURKC	-0.001	0.067	-9999	-0.31	22	22

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-9999	-0.82	1	1
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.66	16	16
PTK2	-0.042	0.16	-9999	-0.6	32	32
positive regulation of JNK cascade	-0.022	0.084	-9999	-0.34	32	32
CDC42/GDP	0.028	0.13	-9999	-0.47	32	32
Rac1/GDP	0.03	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	-0.63	32	32
RAPGEF1	0.02	0.15	-9999	-0.53	32	32
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0.17	-9999	-0.62	32	32
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.82	1	1
TLN1	0.018	0.077	-9999	-0.93	1	1
Rap1/GTP	-0.024	0.09	-9999	-0.37	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	-0.63	32	32
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.021	0.16	-9999	-0.59	32	32
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.82	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	-0.023	0.088	-9999	-0.36	32	32
PVRL1	0.005	0.052	-9999	-0.31	13	13
PVRL3	-0.04	0.2	-9999	-0.82	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	-0.33	407	407
JAM-A/CLDN1	-0.14	0.14	-9999	-0.57	42	42
SRC	-0.047	0.18	-9999	-0.71	32	32
ITGB3	-0.011	0.14	-9999	-0.82	15	15
nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.032	-9999	-10000	0	0
FARP2	0.015	0.16	-9999	-0.58	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	-0.55	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	-0.022	0.084	-9999	-0.34	32	32
alphaV/beta3 Integrin/Talin	0.016	0.13	-9999	-0.6	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	0.01	0.081	-9999	-0.99	1	1
VAV2	0.014	0.16	-9999	-0.59	32	32
RAP1/GDP	-0.028	0.11	-9999	-0.43	32	32
ITGAV	0.01	0.052	-9999	-0.82	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	-0.63	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

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.017	0.085	-9999	-0.47	16	16
RGS9BP	-0.036	0.2	-9999	-0.82	30	30
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.065	0.24	-9999	-0.81	48	48
mol:Na +	-0.022	0.058	-9999	-10000	0	0
mol:ADP	-0.043	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	79	79
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.011	-9999	-10000	0	0
GRK7	0.007	0.007	-9999	-10000	0	0
CNGB3	0.003	0.005	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.015	0.064	-9999	-0.3	2	2
Cone PDE6	-0.077	0.18	-9999	-0.48	79	79
Cone Metarhodopsin II	-0.048	0.15	-9999	-0.51	47	47
Na + (4 Units)	-0.026	0.058	-9999	-0.3	2	2
GNAT2/GDP	-0.076	0.18	-9999	-0.48	79	79
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.015	-9999	-10000	0	0
Cone Transducin	-0.018	0.089	-9999	-0.5	16	16
SLC24A2	-0.01	0.065	-9999	-0.31	22	22
GNB3/GNGT2	-0.022	0.11	-9999	-0.63	16	16
GNB3	-0.012	0.14	-9999	-0.78	16	16
GNAT2/GTP	-0.001	0.013	-9999	-10000	0	0
CNGA3	-0.029	0.11	-9999	-0.31	64	64
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.022	0.058	-9999	-10000	0	0
mol:Pi	-0.088	0.2	-9999	-0.55	79	79
Cone CNG Channel	-0.017	0.043	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.065	-9999	-0.31	22	22
RGS9	-0.073	0.25	-9999	-0.79	54	54
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

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.002	0.039	-9999	-0.63	2	2
Necdin/E2F1	-0.068	0.12	-9999	-0.75	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.035	0.1	-9999	-0.48	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.28	-9999	-0.57	238	238
NT-4/5 (dimer)/p75(NTR)	-0.074	0.18	-9999	-0.66	37	37
IKBKB	0.013	0	-9999	-10000	0	0
AKT1	-0.003	0.12	-9999	-0.48	23	23
IKBKG	0.013	0	-9999	-10000	0	0
BDNF	-0.014	0.14	-9999	-0.61	22	22
MGDIs/NGR/p75(NTR)/LINGO1	-0.048	0.12	-9999	-0.56	18	18
FURIN	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.057	0.14	-9999	-0.56	30	30
LINGO1	-0.003	0.071	-9999	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.025	-9999	-10000	0	0
proBDNF (dimer)	-0.014	0.14	-9999	-0.61	22	22
NTRK1	-0.002	0.062	-9999	-0.31	19	19
RTN4R	0.013	0	-9999	-10000	0	0
neuron apoptosis	-0.01	0.13	-9999	-0.58	8	8
IRAK1	0.013	0	-9999	-10000	0	0
SHC1	-0.02	0.13	-9999	-0.56	20	20
ARHGDIA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.039	0.11	-9999	-0.52	20	20
MAGEH1	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.043	0.12	-9999	-0.51	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-9999	-0.49	25	25
proNGF (dimer)	0.006	0.069	-9999	-0.56	6	6
MAGED1	0.013	0	-9999	-10000	0	0
APP	0.013	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.022	0.16	-9999	-0.66	26	26
ZNF274	0.013	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.036	0.1	-9999	-0.48	20	20
NGF	0.006	0.069	-9999	-0.56	6	6
cell cycle arrest	0.044	0.16	-9999	-0.47	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.085	-9999	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.064	0.16	-9999	-0.58	38	38
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.045	0.12	-9999	-0.56	21	21
PSENEN	0.013	0	-9999	-10000	0	0
mol:ceramide	-0.009	0.12	-9999	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.07	-9999	-0.43	2	2
p75(NTR)/beta APP	-0.049	0.13	-9999	-0.63	18	18
BEX1	-0.36	0.41	-9999	-0.82	223	223
mol:GDP	-0.03	0.13	-9999	-0.57	20	20
NGF (dimer)	-0.094	0.13	-9999	-0.5	31	31
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.042	0.11	-9999	-0.52	18	18
PIK3R1	0.013	0	-9999	-10000	0	0
RAC1/GTP	-0.038	0.1	-9999	-0.5	20	20
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.045	0.12	-9999	-0.56	21	21
RHOB	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.062	0.093	-9999	-10000	0	0
NT3 (dimer)	-0.047	0.2	-9999	-0.6	49	49
TP53	-0.005	0.13	-9999	-0.45	32	32
PRDM4	-0.009	0.12	-9999	-0.51	20	20
BDNF (dimer)	-0.13	0.16	-9999	-0.53	42	42
PIK3CA	0.008	0.064	-9999	-0.82	3	3
SORT1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.034	0.1	-9999	-0.48	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.11	-9999	-0.52	22	22
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	0.024	0.12	-9999	-0.6	4	4
DIABLO	0.013	0	-9999	-10000	0	0
SMPD2	-0.009	0.12	-9999	-0.51	20	20
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.044	0.12	-9999	-0.56	20	20
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-9999	-0.63	1	1
NT3 (dimer)/p75(NTR)	-0.092	0.2	-9999	-0.66	45	45
MAPK8	0.017	0.13	-9999	-0.66	4	4
MAPK9	0.024	0.12	-9999	-0.6	3	3
APAF1	0.012	0.037	-9999	-0.82	1	1
NTF3	-0.047	0.2	-9999	-0.6	49	49
NTF4	-0.022	0.16	-9999	-0.66	26	26
NDN	0.005	0.082	-9999	-0.82	5	5
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.032	0.094	-9999	-0.44	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.053	-9999	-0.65	3	3
RhoA-B-C/GTP	-0.045	0.12	-9999	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.047	0.12	-9999	-0.48	32	32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.052	0.13	-9999	-0.51	32	32
PRKACB	0.012	0.037	-9999	-0.82	1	1
proBDNF (dimer)/p75 ECD	-0.022	0.11	-9999	-0.63	15	15
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.037	0.19	-9999	-0.64	38	38
BIRC2	0.013	0	-9999	-10000	0	0
neuron projection morphogenesis	0.067	0.17	-9999	-0.47	20	20
BAD	0.029	0.12	-9999	-0.59	4	4
RIPK2	0.013	0	-9999	-10000	0	0
NGFR	-0.06	0.18	-9999	-0.42	84	84
CYCS	0	0.11	-9999	-0.48	20	20
ADAM17	0.01	0.052	-9999	-0.82	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.041	0.11	-9999	-0.52	22	22
BCL2L11	0.029	0.12	-9999	-0.59	4	4
BDNF (dimer)/p75(NTR)	-0.069	0.16	-9999	-0.63	32	32
PI3K	-0.041	0.12	-9999	-0.52	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.039	0.11	-9999	-0.52	20	20
NDNL2	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.054	0.14	-9999	-0.65	20	20
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.039	0.11	-9999	-0.52	20	20
TRAF6	0.01	0.052	-9999	-0.82	2	2
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
PLG	-0.004	0.04	-9999	-0.31	8	8
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.016	0.14	-9999	-0.49	32	32
SQSTM1	0.013	0	-9999	-10000	0	0
NGFRAP1	0.013	0	-9999	-10000	0	0
CASP3	0.031	0.11	-9999	-0.53	4	4
E2F1	-0.087	0.15	-9999	-0.31	154	154
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.013	0.058	-9999	-0.53	3	3
NGF (dimer)/TRKA	-0.013	0.063	-9999	-0.63	3	3
MMP7	-0.18	0.22	-9999	-0.37	246	246
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.037	0.11	-9999	-0.49	22	22
MMP3	-0.04	0.11	-9999	-0.31	71	71
APAF-1/Caspase 9	-0.04	0.11	-9999	-0.6	7	7

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.015	-9999	-0.31	1	1
LAT2	-0.018	0.1	-9999	-0.37	6	6
AP1	-0.2	0.28	-9999	-0.63	131	131
mol:PIP3	-0.017	0.15	-9999	-0.51	15	15
IKBKB	0.003	0.093	-9999	-0.29	12	12
AKT1	-0.016	0.14	-9999	-0.58	6	6
IKBKG	0.003	0.093	-9999	-0.29	12	12
MS4A2	-0.065	0.14	-9999	-0.31	115	115
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.82	3	3
MAP3K1	0.01	0.1	-9999	-0.46	7	7
mol:Ca2+	-0.008	0.12	-9999	-0.37	15	15
LYN	0.01	0.007	-9999	-10000	0	0
CBLB	-0.01	0.088	-9999	-0.35	4	4
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.081	0.18	-9999	-0.5	81	81
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	25	25
PLD2	-0.047	0.14	-9999	-0.44	40	40
PTPN13	-0.001	0.1	-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	-0.39	3	3
SYK	0.01	0.007	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.062	0.13	-9999	-0.53	15	15
LAT	-0.014	0.099	-9999	-0.43	8	8
PAK2	0.002	0.11	-9999	-0.51	8	8
NFATC2	-0.15	0.28	-9999	-0.75	87	87
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	-0.098	0.16	-9999	-0.47	67	67
Antigen/IgE/Fc epsilon R1	-0.088	0.15	-9999	-0.43	67	67
mol:GDP	-0.016	0.13	-9999	-0.5	15	15
JUN	-0.17	0.35	-9999	-0.82	113	113
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.043	0.078	-9999	-0.32	8	8
CHUK	0.003	0.093	-9999	-0.28	13	13
KLRG1	-0.021	0.1	-9999	-0.41	14	14
VAV1	-0.023	0.11	-9999	-0.49	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.01	0.088	-9999	-0.35	4	4
negative regulation of mast cell degranulation	-0.019	0.1	-9999	-0.37	15	15
BTK	-0.022	0.12	-9999	-0.59	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.048	0.19	-9999	-0.52	47	47
GAB2/PI3K/SHP2	-0.063	0.13	-9999	-0.6	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.018	0.093	-9999	-0.29	35	35
RAF1	0.018	0.02	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.2	-9999	-0.58	57	57
FCER1G	-0.008	0.082	-9999	-0.32	32	32
FCER1A	-0.074	0.22	-9999	-0.55	76	76
Antigen/IgE/Fc epsilon R1/Fyn	-0.079	0.14	-9999	-0.47	41	41
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.82	1	1
MAPK8	0.005	0.11	-9999	-0.66	11	11
DUSP1	-0.12	0.3	-9999	-0.82	81	81
NF-kappa-B/RelA	-0.019	0.044	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.004	0.082	-9999	-0.38	1	1
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	-0.53	62	62
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.012	0.13	-9999	-0.57	10	10
cytokine secretion	-0.014	0.032	-9999	-0.22	1	1
SPHK1	-0.013	0.091	-9999	-0.38	5	5
PTK2	-0.005	0.085	-9999	-0.39	1	1
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.066	0.13	-9999	-0.56	12	12
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.011	0.14	-9999	-0.49	13	13
MAP2K2	0.025	0.018	-9999	-10000	0	0
MAP2K1	0.025	0.018	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.046	0.092	-9999	-0.42	14	14
MAP2K4	0.021	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.21	-9999	-0.63	52	52
mol:Choline	-0.046	0.14	-9999	-0.44	40	40
SHC/Grb2/SOS1	-0.03	0.065	-9999	-0.4	1	1
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.004	0.08	-9999	-10000	0	0
HCLS1	-0.012	0.093	-9999	-0.38	5	5
PRKCB	-0.01	0.12	-9999	-0.38	22	22
FCGR2B	-0.03	0.18	-9999	-0.73	29	29
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.019	0.11	-9999	-0.38	15	15
LCP2	0.007	0.044	-9999	-0.32	9	9
PLA2G4A	-0.039	0.15	-9999	-0.51	35	35
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.046	0.14	-9999	-0.44	40	40
IKK complex	0.018	0.075	-9999	-0.22	5	5
WIPF1	0.013	0	-9999	-10000	0	0

×

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	77	77
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	-0.084	0.24	-9999	-0.59	81	81
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.005	0.067	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.005	0.082	-9999	-0.82	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.066	0.027	-9999	-10000	0	0
JUN	-0.073	0.22	-9999	-0.44	115	115
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.062	0.13	-9999	-0.47	37	37
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.072	0.14	-9999	-0.51	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	-0.53	35	35
NFKB1	0.012	0.037	-9999	-0.82	1	1
MAPK8	0.019	0.11	-9999	-0.52	19	19
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.044	0.11	-9999	-0.63	11	11
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.052	-9999	-0.82	2	2
PI3K	-0.004	0.048	-9999	-0.63	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	-0.53	35	35
IL1 beta/IL1R2	-0.099	0.22	-9999	-0.6	73	73
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	-0.064	0.13	-9999	-0.48	39	39
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.1	-9999	-0.34	38	38
IL1 alpha/IL1R1/IL1RAP	-0.083	0.15	-9999	-0.56	38	38
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.022	0.035	-9999	-0.47	2	2
IL1RAP	-0.071	0.14	-9999	-0.31	130	130
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.049	0.11	-9999	-0.49	11	11
CASP1	0.007	0.061	-9999	-0.46	7	7
IL1RN/IL1R2	-0.11	0.21	-9999	-0.62	64	64
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	-0.34	4	4
PIK3CA	0.008	0.064	-9999	-0.82	3	3
IL1RN	-0.053	0.16	-9999	-0.38	85	85
TRAF6/TAK1/TAB1/TAB2	-0.002	0.029	-9999	-0.46	2	2
MAP2K6	0.022	0.075	-9999	-0.44	13	13

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.04	0.12	-9999	-0.42	47	47
Syndecan-3/Neurocan	-0.034	0.12	-9999	-0.46	35	35
POMC	-0.16	0.34	-9999	-0.8	106	106
EGFR	0.005	0.082	-9999	-0.82	5	5
Syndecan-3/EGFR	-0.005	0.046	-9999	-0.46	5	5
AGRP	-0.006	0.065	-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	-0.049	0.21	-9999	-0.75	40	40
long-term memory	0	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.04	0.082	-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	-0.31	1	1
PTN	-0.065	0.24	-9999	-0.81	48	48
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	-0.067	0.15	-9999	-0.41	81	81
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	-0.04	0.081	-9999	-0.45	11	11
IL8	-0.083	0.18	-9999	-0.36	131	131
Syndecan-3/Fyn/Cortactin	0	0.006	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.14	0.26	-9999	-0.63	103	103
Gamma Secretase	0	0	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.064	0.081	-10000	0	-0.34	22	22
NT3 (dimer)/TRKC	-0.089	0.19	-10000	0	-0.67	40	40
NT3 (dimer)/TRKB	-0.082	0.18	-10000	0	-0.57	50	50
SHC/Grb2/SOS1/GAB1/PI3K	0.038	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	-0.82	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	0.082	-10000	0	-0.82	5	5
NTRK3	-0.056	0.17	-10000	0	-0.82	13	13
NT-4/5 (dimer)/TRKB	-0.067	0.16	-10000	0	-0.58	41	41
neuron apoptosis	0.04	0.091	0.43	13	-10000	0	13
SHC 2-3/Grb2	-0.042	0.098	-10000	0	-0.47	13	13
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.029	0.091	-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	-0.083	0.17	-10000	0	-0.56	47	47
RIN/GDP	-0.009	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	-0.031	0.09	-10000	0	-0.44	19	19
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	-0.82	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	0.039	-10000	0	-10000	0	0
ELMO1	-0.31	0.4	-10000	0	-0.82	195	195
RhoG/GTP/ELMO1/DOCK1	-0.22	0.27	-10000	0	-0.56	196	196
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	-0.82	4	4
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.014	0.15	-10000	0	-0.79	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.2	0.23	-10000	0	-0.47	210	210
mol:GDP	-0.015	0.088	-10000	0	-0.41	3	3
NGF (dimer)	0.006	0.069	-10000	0	-0.56	6	6
RhoG/GDP	-0.25	0.31	-10000	0	-0.64	195	195
RIT1/GDP	-0.004	0.062	-10000	0	-0.28	2	2
TIAM1	-0.17	0.16	-10000	0	-0.32	282	282
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)	-0.047	0.2	-10000	0	-0.6	49	49
RAP1/GDP	-0.018	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	-0.066	0.14	-10000	0	-0.45	55	55
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	55	55
MAPK3	0.014	0.078	-10000	0	-0.49	8	8
MAPK1	0.014	0.078	-10000	0	-0.49	8	8
CDC42/GDP	-0.004	0.062	-10000	0	-0.28	2	2
NTF3	-0.047	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	-0.63	3	3
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.13	0.11	-10000	0	-0.47	26	26
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.052	0.17	-10000	0	-0.58	40	40
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	0.047	-10000	0	-0.42	1	1
Rac1/GDP	-0.004	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	0.001	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	0.031	0.031	-10000	0	-0.36	3	3
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.02	-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	0.039	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.02	0.097	-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	-0.015	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	199	199
FRS2 family/SHP2/CRK family	-0.001	0.02	-10000	0	-0.46	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.053	0.35	-9999	-0.91	14	14
PLK1	0.044	0.07	-9999	-10000	0	0
BIRC5	0.029	0.12	-9999	-1.5	1	1
HSPA1B	0.053	0.35	-9999	-0.91	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	-1	18	18
XRCC1	0.053	0.35	-9999	-0.92	13	13
FOXM1B/p19	-0.092	0.3	-9999	-0.9	26	26
Cyclin D1/CDK4	0.04	0.33	-9999	-0.91	8	8
CDC2	0.047	0.36	-9999	-0.9	19	19
TGFA	0.024	0.34	-9999	-0.89	11	11
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	14	14
RB1	-0.052	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.038	0.36	-9999	-0.98	19	19
AURKB	-0.005	0.13	-9999	-10000	0	0
CENPF	0.047	0.36	-9999	-0.95	13	13
CDK4	0.019	0.015	-9999	-10000	0	0
MYC	0.046	0.35	-9999	-0.93	20	20
CHEK2	0.032	0.037	-9999	-10000	0	0
ONECUT1	0.037	0.34	-9999	-0.9	14	14
CDKN2A	-0.12	0.16	-9999	-0.31	207	207
LAMA4	0.053	0.35	-9999	-0.92	13	13
FOXM1B/HNF6	0.03	0.37	-9999	-1	14	14
FOS	-0.17	0.65	-9999	-1.2	129	129
SP1	0.014	0.005	-9999	-10000	0	0
CDC25B	0.053	0.35	-9999	-0.9	15	15
response to radiation	0.016	0.034	-9999	-10000	0	0
CENPB	0.053	0.35	-9999	-0.91	14	14
CENPA	0.039	0.37	-9999	-0.97	19	19
NEK2	0.043	0.36	-9999	-0.93	16	16
HIST1H2BA	0.045	0.35	-9999	-0.92	13	13
CCNA2	0.01	0.049	-9999	-0.33	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	-0.94	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	-0.93	8	8
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	0.23	-9999	-0.88	21	21
GAS1	-0.12	0.61	-9999	-1.2	105	105
MMP2	0.044	0.38	-9999	-1.1	16	16
RB1/FOXM1C	0.051	0.34	-9999	-0.92	14	14
CREBBP	0.013	0	-9999	-10000	0	0

×

ErbB4 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	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	-0.34	7	7
epithelial cell differentiation	-0.047	0.1	-10000	0	-0.47	12	12
ITCH	0.024	0.02	-10000	0	-10000	0	0
WWP1	-0.002	0.08	-10000	0	-0.43	1	1
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.005	0.082	-10000	0	-0.82	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	-0.016	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	-0.042	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	-0.52	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.045	0.16	-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	-0.47	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	0.073	-10000	0	-0.31	26	26
PRLR	-0.044	0.19	-10000	0	-0.59	47	47
E4ICDs/ETO2	-0.007	0.092	-10000	0	-0.49	3	3
axon guidance	-0.001	0.086	-10000	0	-0.41	4	4
NEDD4	0.021	0.056	-10000	0	-0.8	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.042	0.14	-10000	0	-0.64	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	-0.004	0.14	-10000	0	-0.53	10	10
STAT1 (dimer)	-0.009	0.091	-10000	0	-0.35	6	6
MAPK1	-0.004	0.14	-10000	0	-0.52	11	11
JAK2	0.01	0.052	-10000	0	-0.82	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.066	0.14	-10000	0	-0.49	46	46
NRG1	-0.032	0.2	-10000	0	-0.64	46	46
NRG3	-0.046	0.21	-10000	0	-0.82	36	36
NRG2	-0.08	0.26	-10000	0	-0.79	58	58
NRG4	0.008	0.036	-10000	0	-0.31	6	6
heart development	-0.001	0.086	-10000	0	-0.41	4	4
neural crest cell migration	-0.032	0.16	-10000	0	-0.49	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	-0.62	5	5
apoptosis	0.058	0.14	0.46	37	-10000	0	37
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.066	0.19	-10000	0	-0.55	57	57
ErbB4/ErbB2/epiregulin	-0.08	0.088	-10000	0	-0.55	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	-0.06	0.14	-10000	0	-0.5	46	46
STAT5A	0.008	0.081	-10000	0	-0.41	3	3
ErbB4/EGFR/neuregulin 1 beta	-0.07	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)	-0.049	0.11	-10000	0	-0.51	12	12
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.079	-10000	0	-0.51	1	1
LRIG1	0	0.1	-10000	0	-0.82	8	8
EREG	-0.14	0.16	-10000	0	-0.31	234	234
BTC	-0.015	0.15	-10000	0	-0.82	17	17
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.086	-10000	0	-0.41	4	4
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	-0.82	1	1
cell proliferation	-0.024	0.17	-10000	0	-0.56	17	17

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.24	0.38	-10000	0	-0.82	152	152
HRAS	0.012	0.021	-10000	0	-0.31	2	2
EGFR	0.005	0.082	-10000	0	-0.82	5	5
AKT	0.019	0.025	-10000	0	-10000	0	0
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.1	0.16	-10000	0	-0.31	182	182
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.013	0.14	-10000	0	-0.73	18	18
PIK3R3	0.012	0.037	-10000	0	-0.82	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.058	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	-0.038	0.095	0.23	1	-0.22	50	51
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.025	0.027	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.037	-10000	0	-0.82	1	1

×

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	66	66
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.056	-10000	0	-0.21	34	34
GNB1/GNG2	-0.001	0.024	-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	-0.52	65	65
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	65	-10000	0	65
GNAL	-0.094	0.28	-10000	0	-0.82	65	65
GNG2	0.012	0.037	-10000	0	-0.82	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	0.068	-10000	0	-0.46	11	11
MAPK11	0.009	0	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.015	0.057	-9999	-0.55	5	5
ADCY5	-0.057	0.2	-9999	-0.55	67	67
ADCY6	0.015	0.057	-9999	-0.55	5	5
ADCY7	0.015	0.057	-9999	-0.55	5	5
ADCY1	0.008	0.089	-9999	-0.62	9	9
ADCY2	-0.039	0.17	-9999	-0.56	47	47
ADCY3	0.015	0.057	-9999	-0.55	5	5
ADCY8	-0.12	0.1	-9999	-0.7	5	5
PRKCE	0.006	0.064	-9999	-0.64	5	5
ADCY9	0.015	0.057	-9999	-0.55	5	5
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.056	0.1	-9999	-0.38	31	31

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.019	0.12	-10000	0	-0.78	12	12
HDAC1	0.002	0.009	-10000	0	-10000	0	0
AES	0.012	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.002	0.097	-10000	0	-0.82	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.008	0.064	-10000	0	-0.82	3	3
AP1	-0.14	0.26	-10000	0	-0.53	140	140
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.007	0.13	-10000	0	-0.82	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.053	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.017	0.11	-10000	0	-0.73	12	12
WIF1	-0.034	0.1	-10000	0	-0.31	62	62
NOTCH1	-0.018	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	-0.042	0.13	-10000	0	-0.33	81	81
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	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.024	0.036	-10000	0	-0.35	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.2	0.36	-10000	0	-0.82	128	128
JUN	-0.17	0.35	-10000	0	-0.82	113	113
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.029	0.04	0.24	13	-10000	0	13
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.12	-10000	0	-0.56	20	20
HNF1A	0.012	0.002	-10000	0	-10000	0	0
CTBP1	0.012	0.002	-10000	0	-10000	0	0
MYC	-0.014	0.25	-10000	0	-1.5	13	13
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	140	140
Delta 1/NOTCHprecursor	-0.018	0.12	-10000	0	-0.76	12	12
DLL1	0.011	0.04	-10000	0	-0.56	2	2
PPARD	0.024	0.017	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.06	-10000	0	-0.65	2	2
DVL1	0.002	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	0.008	-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	0.051	-10000	0	-0.67	1	1
DKK2	-0.026	0.17	-10000	0	-0.66	29	29
NOTCH1 precursor/DVL1	-0.012	0.099	-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	-0.018	0.045	-10000	0	-10000	0	0
RBPJ	0.013	0.015	-10000	0	-0.31	1	1
CREBBP	0.017	0.004	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.014	0.066	-9999	-0.39	3	3
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	-0.014	0.065	-9999	-0.38	3	3
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.015	0.094	-9999	-0.33	40	40
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.11	0.16	-9999	-0.39	64	64
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	223	223
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

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.82	3	3
JAK3	-0.067	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	-0.58	18	18
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.044	0.25	-9999	-0.98	32	32
IL2RB	-0.013	0.13	-9999	-0.5	27	27
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.047	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	-0.82	1	1
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.009	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	-0.82	3	3
CCND3	0.028	0.13	-9999	-0.62	8	8

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.057	0.15	-9999	-0.44	62	62
TC10/GTP	-0.004	0.042	-9999	-0.42	5	5
Insulin Receptor/Insulin/IRS1/Shp2	-0.063	0.17	-9999	-0.51	62	62
HRAS	0.012	0.021	-9999	-0.31	2	2
APS homodimer	0.011	0.04	-9999	-0.82	1	1
GRB14	-0.012	0.14	-9999	-0.82	15	15
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	-0.002	0.033	-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	-0.82	4	4
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.035	0.035	-9999	-0.41	3	3
CAV1	-0.046	0.18	-9999	-0.47	75	75
CBL/APS/CAP/Crk-II/C3G	-0.005	0.046	-9999	-0.46	5	5
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	-0.057	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	-0.051	0.13	-9999	-0.49	4	4
Insulin Receptor	0.015	0.003	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.058	0.15	-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	76	76
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.004	-9999	-10000	0	0
PI3K	-0.058	0.15	-9999	-0.46	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	-0.21	2	2
AKT2	-0.015	0.16	-9999	-0.44	17	17
PRKCZ	-0.015	0.034	-9999	-10000	0	0
SH2B2	0.011	0.04	-9999	-0.82	1	1
SHC/SHIP	-0.031	0.16	-9999	-0.45	62	62
F2RL2	-0.08	0.16	-9999	-0.32	138	138
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	-0.005	0.049	-9999	-0.49	5	5
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.003	0.036	-9999	-0.46	3	3
INPP5D	-0.041	0.17	-9999	-0.48	62	62
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.024	0.14	-9999	-1	10	10
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.82	1	1
IRS1	-0.084	0.27	-9999	-0.82	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	-0.04	0.17	-9999	-0.48	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	-0.82	3	3
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0.052	-9999	-0.82	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.009	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	-0.036	0.064	-9999	-0.47	3	3

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-10000	0	0
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	-0.36	0.41	-10000	0	-0.82	223	223
FHL2	-0.051	0.22	-10000	0	-0.82	39	39
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.03	-10000	0	-0.63	1	1
HIST2H4A	0.021	0.029	-10000	0	-0.63	1	1
SIRT1/FOXO3a	0	0.026	-10000	0	-0.55	1	1
SIRT1	0	0.038	-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	223	223
p53/SIRT1	0.004	0.042	-10000	0	-0.63	1	1
SIRT1/FOXO4	0.001	0.026	-10000	0	-0.53	1	1
FOXO1/FHL2/SIRT1	-0.038	0.14	-10000	0	-0.5	40	40
HIST1H1E	0.015	0.053	-10000	0	-0.36	9	9
SIRT1/p300	0.001	0.03	-10000	0	-0.63	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	-0.63	1	1
ACSS2	0.021	0.029	-10000	0	-0.63	1	1
SIRT1/PCAF/MYOD	-0.001	0.03	-10000	0	-0.55	1	1

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.34	-9999	-0.82	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	-0.003	0.04	-9999	-0.51	3	3
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.12	0.16	-9999	-0.31	207	207
ARNT/IPAS	-0.13	0.25	-9999	-0.63	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	-0.82	3	3
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.023	-9999	-10000	0	0
EGLN3	-0.019	0.14	-9999	-0.49	32	32
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.01	0.052	-9999	-0.82	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	-0.03	0.073	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.003	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

×

Aurora B signaling

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
Condensin I complex	-0.001	0.08	-9999	-10000	0	0
STMN1	-0.022	0.095	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.024	0.11	-9999	-0.33	31	31
Chromosomal passenger complex/Cul3 protein complex	0.007	0.07	-9999	-0.29	14	14
BIRC5	-0.011	0.092	-9999	-0.34	35	35
DES	-0.38	0.3	-9999	-0.61	304	304
Aurora C/Aurora B/INCENP	-0.017	0.088	-9999	-0.64	2	2
Aurora B/TACC1	-0.022	0.081	-9999	-0.71	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	-0.047	0.14	-9999	-0.39	57	57
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	0.008	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	0.006	0.045	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
H3F3B	-0.008	0.055	-9999	-10000	0	0
AURKB	-0.052	0.14	-9999	-0.31	114	114
AURKC	-0.001	0.067	-9999	-0.31	22	22
CDCA8	0.01	0.031	-9999	-0.33	4	4
cytokinesis	-0.065	0.082	-9999	-0.43	5	5
Aurora B/Septin1	-0.026	0.1	-9999	-0.45	7	7
AURKA	0.013	0.002	-9999	-10000	0	0
INCENP	0.009	0.053	-9999	-0.83	2	2
KLHL13	-0.016	0.14	-9999	-0.54	27	27
BUB1	-0.1	0.16	-9999	-0.82	1	1
hSgo1/Aurora B/Survivin	-0.024	0.12	-9999	-0.45	16	16
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.03	0.072	-9999	-0.37	4	4
SGOL1	0.001	0.062	-9999	-0.31	19	19
CENPA	-0.008	0.07	-9999	-0.24	9	9
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	0.091	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.034	0.08	-9999	-0.36	17	17
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.048	-9999	-10000	0	0
MYLK	-0.009	0.06	-9999	-0.55	1	1
KIF23	-0.004	0.074	-9999	-0.32	26	26
VIM	-0.022	0.093	-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	0.082	-9999	-0.26	23	23
Chromosomal passenger complex/EVI5	0.011	0.12	-9999	-0.47	7	7
TACC1	0.012	0.037	-9999	-0.82	1	1
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.016	0.15	-9999	-0.7	21	21
mol:Sphinganine-1-P	0.019	0.035	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.002	0.014	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.013	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.011	-9999	-10000	0	0
S1PR5	0.007	0.053	-9999	-0.38	8	8
S1PR4	0.009	0.038	-9999	-0.31	7	7
GNAI1	0.012	0.037	-9999	-0.82	1	1
S1P/S1P5/G12	-0.004	0.028	-9999	-0.48	1	1
S1P/S1P3/Gq	-0.051	0.16	-9999	-0.31	127	127
S1P/S1P4/Gi	0.031	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	-0.82	120	120
GNA15	-0.012	0.093	-9999	-0.33	38	38
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.12	-9999	-0.82	10	10
ABCC1	0.013	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.024	0.15	-9999	-0.52	35	35
ITGA4	0.003	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	-0.63	3	3

×

Ceramide signaling pathway

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
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	-0.82	1	1
PKC zeta/ceramide	-0.018	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.64	38	38
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	-0.017	0.04	-10000	0	-10000	0	0
SMPD1	-0.005	0.095	-10000	0	-0.26	58	58
RB1	-0.018	0.046	-10000	0	-0.5	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	-0.028	0.043	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.023	0.029	-10000	0	-0.63	1	1
ASAH1	0.012	0.037	-10000	0	-0.82	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	115	115
BID	-0.015	0.091	-10000	0	-0.4	11	11
MAP3K1	-0.017	0.04	-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	-0.55	2	2
MAPK8	-0.01	0.06	-10000	0	-0.32	11	11
PRKRA	-0.017	0.04	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.18	0.35	-10000	0	-0.79	120	120
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.043	-10000	0	-10000	0	0
CTSD	0.013	0.015	-10000	0	-0.31	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.028	-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	115	115
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	-0.63	1	1
RelA/NF kappa B1	-0.001	0.028	-10000	0	-0.63	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.011	0.15	-10000	0	-0.74	11	11
TNFR1A/BAG4/TNF-alpha	-0.066	0.17	-10000	0	-0.54	59	59
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.002	0.047	-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	0.004	0.053	0.18	29	-10000	0	29
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.012	0.037	-10000	0	-0.82	1	1
TNFR1A/BAG4	-0.001	0.028	-10000	0	-0.63	1	1
EIF2AK2	-0.009	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.065	0.17	-10000	0	-0.54	58	58
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.078	-10000	0	-0.33	11	11
MAP2K2	-0.002	0.047	-10000	0	-0.48	2	2
SMPD3	-0.011	0.12	-10000	0	-0.3	63	63
TNF	-0.088	0.27	-10000	0	-0.76	65	65
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.023	0.11	0.28	72	-10000	0	72
NF kappa B1/RelA/I kappa B alpha	-0.001	0.02	-10000	0	-0.46	1	1
AIFM1	0.004	0.053	0.18	29	-10000	0	29
BCL2	-0.05	0.22	-10000	0	-0.82	38	38

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0.12	-10000	0	-0.75	3	3
UGCG	-0.034	0.18	-10000	0	-0.8	25	25
AKT1/mTOR/p70S6K/Hsp90/TERT	0.018	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	-0.06	0.14	-10000	0	-0.45	38	38
FRAP1	0	0.2	-10000	0	-0.53	38	38
FOXO3	0.018	0.16	-10000	0	-0.59	19	19
AKT1	0.009	0.18	-10000	0	-0.65	19	19
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	0.005	0.03	-10000	0	-10000	0	0
SGMS1	0.005	0.03	-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	-0.004	0.16	-10000	0	-0.49	30	30
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	0.003	-10000	0	-0.013	1	1
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	-0.82	1	1
MYC	0.007	0.22	-10000	0	-0.94	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	-0.57	23	23
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	-0.55	23	23
Rac1/GDP	0.024	0.042	-10000	0	-0.5	3	3
T cell proliferation	0.016	0.15	-10000	0	-0.52	21	21
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	-0.054	16	16
PRKCZ	0.015	0.15	-10000	0	-0.54	21	21
NF kappa B1 p50/RelA	-0.059	0.14	-10000	0	-0.46	31	31
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.001	0.13	-10000	0	-0.6	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.048	0.2	-10000	0	-0.6	50	50
IL2RB	-0.012	0.13	-10000	0	-0.5	27	27
TERT	-0.002	0.043	-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	0.016	0.15	-10000	0	-0.52	21	21
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	-0.029	0.29	-10000	0	-0.83	50	50

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.026	-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	-0.027	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	0.065	-10000	0	-0.45	3	3
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.034	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	0.2	1	-0.35	3	4
MAP3K5	0.011	0.021	-10000	0	-0.45	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.021	-10000	0	-0.45	1	1
mol:LY294002	0	0.001	0.001	1	-0.002	58	59
EIF4B	0.017	0.055	-10000	0	-0.34	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.013	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	0.021	0.04	0.18	1	-0.28	2	3
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.022	0.064	-10000	0	-0.44	3	3
mol:Amino Acids	0	0.001	0.001	1	-0.002	58	59
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.04	0.12	0.26	1	-0.33	61	62
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.033	-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	1	59
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	-0.82	3	3
PTEN	0.011	0.037	-10000	0	-0.82	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	0.009	0.064	-10000	0	-0.82	3	3
PPP2R5D	0.015	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.015	0.039	-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

×

IFN-gamma 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.028	0.16	-9999	-0.43	68	68
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	-0.049	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+	-0.057	0.14	-9999	-0.4	67	67
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.021	0.16	-9999	-0.48	7	7
AKT1	-0.003	0.15	-9999	-0.62	3	3
MAP2K1	-0.007	0.15	-9999	-0.5	6	6
MAP3K11	-0.018	0.16	-9999	-0.41	67	67
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.026	0.068	-9999	-0.63	1	1
Rap1/GTP	-0.042	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	-0.064	0.16	-9999	-0.45	67	67
CEBPB	0.016	0.18	-9999	-0.81	6	6
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.06	0.15	-9999	-1.1	2	2
STAT1	-0.02	0.16	-9999	-0.48	7	7
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.11	0.28	-9999	-0.72	81	81
PIK3CA	0.008	0.064	-9999	-0.82	3	3
STAT1 (dimer)/PIAS1	-0.011	0.15	-9999	-0.79	1	1
CEBPB/PTGES2/Cbp/p300	-0.035	0.083	-9999	-0.44	6	6
mol:Ca2+	-0.061	0.15	-9999	-0.43	68	68
MAPK3	0.009	0.14	-9999	-0.52	6	6
STAT1 (dimer)	-0.032	0.081	-9999	-0.42	2	2
MAPK1	0.009	0.14	-9999	-0.52	6	6
JAK2	0.006	0.055	-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	0.016	0.18	-9999	-0.66	24	24
SMAD7	0.04	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.05	0.12	-9999	-0.76	1	1
PI3K	-0.057	0.14	-9999	-0.5	9	9
IFNG	-0.11	0.28	-9999	-0.72	81	81
apoptosis	0.013	0.13	-9999	-0.45	24	24
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.005	0.069	-9999	-0.31	24	24
CAMK2B	0.004	0.09	-9999	-0.82	6	6
FRAP1	-0.001	0.14	-9999	-0.56	3	3
PRKCD	-0.003	0.15	-9999	-0.63	3	3
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.024	0.061	-9999	-0.3	2	2
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
IRF1	0.028	0.12	-9999	-0.53	1	1
STAT1 (dimer)/PIASy	-0.055	0.13	-9999	-0.79	1	1
SOCS1	0.001	0.074	-9999	-1.5	1	1
mol:GDP	-0.049	0.12	-9999	-0.71	1	1
CASP1	0.038	0.063	-9999	-0.35	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.041	0.058	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.055	0.13	-9999	-0.48	9	9
RAP1/GDP	-0.042	0.1	-9999	-0.6	1	1
CBL	-0.018	0.16	-9999	-0.4	67	67
MAP3K1	-0.017	0.16	-9999	-0.49	7	7
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	-0.028	0.16	-9999	-0.43	68	68
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-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	-0.63	28	28
ATM	0.012	0.037	-10000	0	-0.82	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.012	0.037	-10000	0	-0.82	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.029	-10000	0	-0.44	2	2
protein ubiquitination	-0.026	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	-0.82	3	3
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.013	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0	0	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.035	0.14	-10000	0	-0.63	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	-0.001	0.067	-10000	0	-0.31	22	22
DNA repair	0.052	0.1	-10000	0	-0.52	1	1
BRCA1/BARD1/ubiquitin	-0.035	0.14	-10000	0	-0.63	28	28
BARD1/DNA-PK	-0.027	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	0.091	-10000	0	-0.58	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.03	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/P53	-0.028	0.12	-10000	0	-0.49	29	29
BARD1/CSTF1/BRCA1	-0.03	0.12	-10000	0	-0.54	28	28
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.033	0.19	-10000	0	-0.82	28	28
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.03	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/UbcH7	-0.03	0.12	-10000	0	-0.54	28	28
BRCA1/BARD1/RAD51/PCNA	-0.028	0.11	-10000	0	-0.5	28	28
BARD1/DNA-PK/P53	-0.026	0.1	-10000	0	-0.46	28	28
BRCA1/BARD1/Ubiquitin	-0.035	0.14	-10000	0	-0.63	28	28
BRCA1/BARD1/CTIP	-0.028	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	-0.63	28	28
RBBP8	0.023	0.029	-10000	0	-0.63	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.028	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	-0.035	0.15	-10000	0	-0.64	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	-0.63	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	-0.82	10	10
ANTXR2	0.008	0.064	-10000	0	-0.82	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	61	61
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.014	-10000	0	-10000	0	0
MAP2K7	-0.002	0.014	-10000	0	-10000	0	0
MAP2K6	-0.013	0.074	-10000	0	-0.5	11	11
CYAA	0.004	0.079	-10000	0	-0.48	13	13
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.018	0.12	-10000	0	-0.46	35	35
Channel	-0.013	0.081	-10000	0	-0.51	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	-0.46	14	14
PA/Cellular Receptors	-0.014	0.087	-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	-0.48	13	13
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.088	0.27	-10000	0	-0.76	65	65
VCAM1	-0.047	0.17	-10000	0	-0.48	61	61
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

×

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

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
BAG4	0.012	0.037	-9999	-0.82	1	1
Caspase 8 (4 units)	-0.022	0.063	-9999	-10000	0	0
NEF	-0.012	0.055	-9999	-10000	0	0
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	-0.005	0.2	-9999	-0.81	26	26
CYCS	-0.004	0.1	-9999	-0.4	7	7
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.039	0.19	-9999	-0.7	30	30
MAP2K7	0.024	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	0.079	-9999	-0.34	26	26
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.012	0.037	-9999	-0.82	1	1
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.022	0.08	-9999	-0.35	26	26
MAPK8	0.021	0.1	-9999	-0.41	11	11
APAF1	0.012	0.037	-9999	-0.82	1	1
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.098	-9999	-0.31	30	30
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.025	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	0.02	-9999	-0.46	1	1
TCRz/NEF	-0.061	0.18	-9999	-0.52	54	54
TNF	-0.088	0.27	-9999	-0.76	65	65
FASLG	-0.073	0.29	-9999	-0.86	54	54
NFKB1	0.007	0.047	-9999	-0.81	1	1
TNFR1A/BAG4/TNF-alpha	-0.066	0.17	-9999	-0.54	59	59
CASP6	-0.005	0.045	-9999	-10000	0	0
CASP7	0.029	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	0.029	0.16	-9999	-0.62	25	25
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.028	-9999	-0.63	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.098	-9999	-10000	0	0
APAF-1/Caspase 9	-0.047	0.12	-9999	-0.52	25	25
BCL2	-0.005	0.15	-9999	-0.4	46	46

×

Stabilization and expansion of the E-cadherin adherens junction

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
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	0.082	-9999	-0.82	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	0.074	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	78	78
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.071	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	0.033	-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	-0.066	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	120	120
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	0.059	-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	-0.038	0.075	-9999	-10000	0	0
HGF/MET	-0.1	0.16	-9999	-0.47	75	75
HGF	-0.11	0.3	-9999	-0.82	75	75
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	-0.42	1	1
KIFC3	0.041	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.04	0.007	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.041	0	-9999	-10000	0	0
PIP5K1C	0.041	0	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.064	0.019	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.097	0.18	-9999	-0.42	114	114
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	182	182
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	0.067	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.033	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.047	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.033	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.033	0.3	1	-0.47	2	3
DAPP1	-0.055	0.14	-10000	0	-0.49	12	12
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.06	0.18	-10000	0	-0.58	19	19
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	0.022	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	-0.82	1	1
ARHGEF7	0.013	0	-10000	0	-10000	0	0
ARF1	0.013	0	-10000	0	-10000	0	0
NRAS	0.014	0.001	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
FGR	0.011	0.029	-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	-0.32	282	282
ZAP70	-0.026	0.16	-10000	0	-0.62	31	31
mol:IP3	0.004	0.072	-10000	0	-0.21	2	2
LYN	0.013	0	-10000	0	-10000	0	0
ARF1/GDP	0.022	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	-0.31	1	1
PLEKHA2	0.022	0.041	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.001	0.035	-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	-0.6	14	14
BLK	-0.25	0.37	-10000	0	-0.75	171	171
PDPK1	0.01	0.052	-10000	0	-0.82	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	-10000	0	-0.6	10	10
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	0.022	0.035	-10000	0	-0.46	1	1
LAT	0.005	0.077	-10000	0	-0.82	4	4
Rac1/GTP	-0.007	0.055	-10000	0	-0.47	2	2
ITK	-0.055	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

×

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	0.096	-9999	-0.51	1	1
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.28	0.45	-9999	-0.92	152	152
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	0	0.068	-9999	-0.29	23	23
ER alpha/Oestrogen	-0.041	0.14	-9999	-0.63	23	23
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	0.006	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.036	0.073	-9999	-10000	0	0
SAP18	0.014	0	-9999	-10000	0	0
MRN complex	-0.003	0.042	-9999	-0.54	3	3
WT1	-0.026	0.1	-9999	-0.31	56	56
WRN	0.012	0.037	-9999	-0.82	1	1
SP1	0.015	0.003	-9999	-10000	0	0
SP3	0.014	0.002	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.03	0.057	-9999	-10000	0	0
Mad/Max	0.006	0.01	-9999	-10000	0	0
TERT	-0.025	0.097	-9999	-0.52	1	1
CCND1	-0.016	0.096	-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	-0.82	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	0.02	-9999	-10000	0	0
CDKN1B	-0.04	0.19	-9999	-0.52	66	66
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	-0.82	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	-0.82	113	113
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.003	0.006	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
IFN-gamma/IRF1	-0.086	0.21	-9999	-0.61	67	67
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	-0.045	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	0.015	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	-0.82	3	3
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.032	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	-0.82	1	1
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.025	-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	-0.098	0.22	-9999	-0.62	77	77
MYC	-0.008	0.13	-9999	-0.82	13	13
IL2	0.006	0.007	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.008	0.041	-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	0.057	-9999	-10000	0	0
Smad3/Myc	0.01	0.094	-9999	-0.55	13	13
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.1	0.28	-9999	-0.71	81	81
Telomerase/PinX1	-0.03	0.057	-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	0.057	-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	0.057	-9999	-10000	0	0
E2F1	-0.086	0.15	-9999	-0.31	154	154
ZNFX1	0.014	0	-9999	-10000	0	0
PIF1	0.001	0.095	-9999	-0.62	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

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.017	0.093	-10000	0	-0.46	13	13
ACTA1	0.008	0.12	-10000	0	-0.6	12	12
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	-0.64	38	38
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-10000	0	0
CASP10	-0.003	0.12	-10000	0	-0.59	16	16
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	-0.61	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	60	60
BID	-0.01	0.069	-10000	0	-0.31	13	13
MAP3K1	0.013	0.042	-10000	0	-0.24	2	2
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-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	2	-0.23	22	24
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	-0.82	1	1
CASP6	0.021	0.064	-10000	0	-0.43	4	4
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.02	0.11	-10000	0	-0.59	11	11
CASP7	0.01	0.079	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	-0.17	2	24
actin filament polymerization	-0.02	0.11	0.56	11	-10000	0	11
TNF	-0.088	0.27	-10000	0	-0.76	65	65
CYCS	0.004	0.047	-10000	0	-0.22	13	13
SATB1	0.028	0.061	-10000	0	-0.42	3	3
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	0.24	2	-10000	0	2
CASP3	0.005	0.12	-10000	0	-0.61	13	13
LMNB2	0.021	0.075	-10000	0	-0.32	4	4
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.49	25	25
negative regulation of DNA binding	-0.054	0.22	-10000	0	-0.64	60	60
stress fiber formation	0.01	0.12	-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	-0.32	4	4
APP	0.023	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	0.02	0.1	-10000	0	-0.5	11	11
LMNA	0.021	0.075	-10000	0	-0.32	4	4
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	-0.33	3	3
PRF1	-0.003	0.11	-10000	0	-0.69	12	12

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-0.31	1	1
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.06	-10000	0	-0.34	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	7	-0.41	15	22
RAR alpha/9cRA/Cyclin H	-0.021	0.087	-10000	0	-0.61	3	3
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.067	-10000	0	-0.32	14	14
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.014	0.12	-10000	0	-0.7	11	11
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.016	0.15	-10000	0	-0.62	24	24
NCOA2	-0.066	0.24	-10000	0	-0.82	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	-0.82	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	-0.34	28	28
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.14	-10000	0	-0.41	35	35
PRKCA	-0.015	0.16	-10000	0	-0.82	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	0.015	0.088	-10000	0	-0.33	28	28
RXRB	0.009	0.09	-10000	0	-0.44	19	19
VDR/Vit D3/DNA	0	0.01	-10000	0	-10000	0	0
RBP1	-0.004	0.11	-10000	0	-0.66	13	13
CRBP1/9-cic-RA	-0.013	0.086	-10000	0	-0.64	9	9
RARB	-0.008	0.14	-10000	0	-0.82	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	0.03	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	-0.48	5	5
NRIP1	-0.023	0.14	-10000	0	-0.64	16	16
RXRs/RARs	-0.034	0.15	-10000	0	-0.64	24	24
RXRs/RXRs/DNA/9cRA	-0.044	0.13	-10000	0	-0.69	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

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-9999	-0.82	1	1
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.057	-9999	-0.27	17	17
GNAO1	-0.014	0.15	-9999	-0.7	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	-0.82	1	1
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.013	0.037	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.036	0.066	-9999	-0.31	16	16
MAPK3	0.042	0.063	-9999	-10000	0	0
MAPK1	0.042	0.063	-9999	-10000	0	0
JAK2	0.045	0.065	-9999	-0.42	1	1
CXCR4	0.041	0.064	-9999	-10000	0	0
FLT1	0.015	0.037	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.042	0.063	-9999	-10000	0	0
S1P/S1P3/Gi	0.036	0.066	-9999	-0.32	16	16
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.01	0.05	-9999	-10000	0	0
VEGFA	0.012	0.064	-9999	-0.82	3	3
S1P/S1P2/Gi	0.03	0.067	-9999	-0.32	16	16
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	127	127
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.015	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	120	120
GNA15	-0.012	0.093	-9999	-0.33	38	38
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.12	-9999	-0.82	10	10
Rac1/GTP	-0.01	0.05	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.006	0.075	-9999	-0.72	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	-0.82	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	0.056	-9999	-0.63	4	4
TRAIL/TRAILR3	-0.06	0.1	-9999	-0.67	4	4
TRAIL/TRAILR1	-0.009	0.074	-9999	-0.63	7	7
TRAIL/TRAILR4	-0.005	0.056	-9999	-0.63	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	-0.003	0.03	-9999	-10000	0	0
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.064	-9999	-0.82	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	0.043	0.081	-9999	-0.46	11	11
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.075	0.14	-9999	-0.31	135	135
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	0.05	-9999	-0.52	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	-0.075	0.14	-9999	-0.31	135	135
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.007	0.055	-9999	-0.47	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	0.037	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 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
MAP4K4	0.006	0.13	-10000	0	-0.56	11	11
BAG4	0.012	0.037	-10000	0	-0.82	1	1
BAD	0.018	0.045	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.64	38	38
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	0.022	0.08	-10000	0	-0.43	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	-0.63	1	1
TNF	-0.088	0.27	-10000	0	-0.76	65	65
CYCS	0.028	0.056	0.16	31	-10000	0	31
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	0.028	0.056	0.16	31	-10000	0	31
TNF/TNF R/SODD	-0.066	0.17	-10000	0	-0.54	59	59
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	-0.05	0.22	-10000	0	-0.82	38	38

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	0.013	0	-10000	0	-10000	0	0
NFATC1	0.047	0.058	-10000	0	-0.38	8	8
NFATC2	-0.019	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	0.087	-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	-0.048	0.17	-10000	0	-0.63	38	38
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	-10000	0	0
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.018	0.083	-10000	0	-0.56	4	4
Calcineurin A alpha-beta B1/BCL2	-0.049	0.22	-10000	0	-0.82	38	38
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	-0.82	15	15
MAP3K8	-0.002	0.097	-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	-0.34	149	149
CABIN1	0.014	0.088	-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	-0.008	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	-0.006	0.05	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.006	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.015	0.051	-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	-0.37	46	46
PRKCE	0.005	0.082	-10000	0	-0.82	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	-0.82	19	19
PRKCG	0.005	0.026	-10000	0	-0.31	3	3
PRKCQ	0.003	0.09	-10000	0	-0.82	6	6
FKBP38/BCL2	-0.047	0.17	-10000	0	-0.63	38	38
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	-0.41	3	3
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	0.069	-10000	0	-0.56	7	7
NFATc/ERK1	0.052	0.055	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.023	0.088	-10000	0	-0.52	9	9
NR4A1	-0.18	0.36	-10000	0	-0.73	149	149
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	0.063	-10000	0	-0.4	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	-10000	0	0
CREBBP	0.01	0.007	-10000	0	-10000	0	0
BCL2	-0.05	0.22	-10000	0	-0.82	38	38

×

Circadian rhythm 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
chromatin modification	-0.026	0.048	-9999	-0.63	1	1
CLOCK	-0.044	0.21	-9999	-0.82	33	33
TIMELESS/CRY2	-0.005	0.065	-9999	-10000	0	0
DEC1/BMAL1	-0.025	0.068	-9999	-10000	0	0
ATR	0.012	0.037	-9999	-0.82	1	1
NR1D1	-0.057	0.13	-9999	-10000	0	0
ARNTL	-0.026	0.1	-9999	-0.32	57	57
TIMELESS	-0.013	0.074	-9999	-10000	0	0
NPAS2	0.009	0.04	-9999	-0.56	2	2
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.007	0.03	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.007	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	-0.057	0.16	-9999	-0.5	33	33
S phase of mitotic cell cycle	-0.026	0.048	-9999	-0.63	1	1
TIMELESS/CHEK1/ATR	-0.026	0.048	-9999	-0.64	1	1
mol:NADPH	-0.007	0.03	-9999	-10000	0	0
PER1/TIMELESS	-0.005	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

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.06	0.16	-9999	-0.5	59	59
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.15	-9999	-0.41	59	59
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.024	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	58	58
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	58	58
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	-0.29	59	59
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	-0.82	3	3
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	-0.007	0.099	-9999	-0.28	58	58
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	-0.82	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.015	0.084	-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	-0.46	63	63
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.001	0.089	-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	-0.28	58	58
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	-0.82	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.043	-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	-0.28	58	58
histone deacetylation	0.049	0.019	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.012	0.084	-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	0.089	-9999	-10000	0	0
GATA1/HDAC1	0	0.009	-9999	-10000	0	0
GATA1/HDAC3	-0.009	0.089	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.075	0.2	-9999	-0.63	58	58
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	0.065	-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	-0.088	0.27	-9999	-0.76	65	65
negative regulation of cell growth	0.049	0.022	-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	-0.44	58	58
SIN3/HDAC complex/NCoR1	0.046	0.026	-9999	-10000	0	0
TFCP2	0.007	0.074	-9999	-0.82	4	4
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

Figure S102. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S102. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.023	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	-0.026	0.17	-10000	0	-0.66	29	29
TLE1	0	0.065	-10000	0	-0.8	3	3
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.047	0.04	-10000	0	-10000	0	0
WIF1	-0.035	0.1	-10000	0	-0.31	62	62
beta catenin/RanBP3	0.022	0.091	0.37	25	-10000	0	25
KREMEN2	-0.01	0.083	-10000	0	-0.31	35	35
DKK1	-0.042	0.13	-10000	0	-0.33	81	81
beta catenin/beta TrCP1	0.052	0.038	-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	0.063	0.044	-10000	0	-0.41	1	1
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	-0.031	0.26	-10000	0	-1.6	13	13
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.12	-10000	0	-0.56	20	20
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	28	-10000	0	28
LEF1	-0.003	0.066	-10000	0	-0.41	10	10
DVL1	0.019	0.028	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.067	0.074	-10000	0	-0.5	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	-0.81	1	1
WNT1	0.008	0.033	-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	0.038	-10000	0	-10000	0	0
CREBBP	0.006	0.021	0.2	1	-10000	0	1

×

Arf6 downstream 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
PLAUR	-0.062	0.13	-10000	0	-10000	0	0
regulation of axonogenesis	-0.01	0.037	0.32	2	-10000	0	2
myoblast fusion	0.024	0.053	-10000	0	-10000	0	0
mol:GTP	-0.027	0.04	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.093	0.11	0.52	1	-10000	0	1
ARF1/GTP	-0.016	0.023	-10000	0	-10000	0	0
mol:GM1	-0.011	0.034	-10000	0	-10000	0	0
mol:Choline	0.011	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.004	0.065	-10000	0	-10000	0	0
MAPK3	-0.018	0.066	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.094	0.11	-10000	0	-0.52	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.024	0.053	-10000	0	-10000	0	0
ARF1/GDP	0.003	0.06	-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	0.17	-10000	0	-0.32	282	282
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.018	0.066	-10000	0	-10000	0	0
actin filament bundle formation	0.026	0.039	-10000	0	-10000	0	0
KALRN	-0.006	0.052	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.026	0.039	-10000	0	-10000	0	0
NME1	0.01	0.007	-10000	0	-10000	0	0
Rac1/GDP	-0.026	0.039	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.027	0.04	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.065	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.027	0.04	-10000	0	-10000	0	0
ARF6/GTP	-0.027	0.04	-10000	0	-10000	0	0
RhoA/GTP	-0.016	0.023	-10000	0	-10000	0	0
mol:GDP	-0.012	0.066	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.01	0.015	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0	0.034	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.065	-10000	0	-10000	0	0
ruffle organization	0.01	0.037	-10000	0	-0.32	2	2
regulation of epithelial cell migration	-0.027	0.04	-10000	0	-10000	0	0
PLD2	0	0.034	-10000	0	-10000	0	0
PIP5K1A	0.01	0.037	-10000	0	-0.32	2	2
mol:Phosphatidic acid	0.011	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.065	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.003	0.076	-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	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.041	0.077	0.23	16	-0.27	11	27
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	-0.065	0.22	-10000	0	-0.63	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	65	65
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	-10000	0	2
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	-0.82	15	15
LNPEP	-0.013	0.15	-10000	0	-0.82	16	16
YWHAE	0.013	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.009	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	-0.82	4	4
ITGA4	0.003	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	-0.63	3	3
EPO/EPOR (dimer)	-0.007	0.037	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.037	-9999	-0.46	3	3
PIK3CA	0.008	0.064	-9999	-0.82	3	3
PI3K	-0.004	0.048	-9999	-0.63	3	3
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.023	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	0.023	0.078	-9999	-0.56	7	7
ITGB7	-0.024	0.15	-9999	-0.52	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	0.04	0.079	-9999	-0.44	11	11
VCAM1	0.002	0.088	-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	-0.52	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

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.08	-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	0.016	0.14	-9999	-0.66	9	9
GNAO1	-0.016	0.15	-9999	-0.7	21	21
PDGFB-D/PDGFRB/PLCgamma1	0.025	0.13	-9999	-0.57	9	9
PLCG1	0.023	0.13	-9999	-0.64	8	8
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.82	1	1
GNAI2	0.014	0.004	-9999	-10000	0	0
GNAI3	0.013	0.004	-9999	-10000	0	0
GNAI1	0.012	0.037	-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	-0.015	0.066	-9999	-0.5	6	6
negative regulation of cAMP metabolic process	0.017	0.14	-9999	-0.64	9	9
MAPK3	0.01	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	0.031	0.072	-9999	-0.44	6	6
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.053	-9999	-0.41	6	6
receptor internalization	-0.015	0.061	-9999	-0.46	6	6
PTGS2	-0.028	0.32	-9999	-1.1	40	40
Rac1/GTP	-0.013	0.053	-9999	-0.41	6	6
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.064	-9999	-0.82	3	3
negative regulation of T cell proliferation	0.017	0.14	-9999	-0.64	9	9
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.004	-9999	-10000	0	0
MAPK1	0.01	0.19	-9999	-0.57	41	41
S1P1/S1P/PDGFB-D/PDGFRB	0.033	0.086	-9999	-0.5	7	7
ABCC1	0.014	0.002	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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
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	-0.63	2	2
NFKBIA	0.049	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	-0.006	0.02	-9999	-10000	0	0
IKK complex/A20	-0.048	0.13	-9999	-0.64	2	2
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.038	-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	-0.034	0.12	-9999	-0.33	69	69
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	-0.82	1	1
TNF/TNFR1A	-0.075	0.2	-9999	-0.63	58	58
TRAF6	0.01	0.052	-9999	-0.82	2	2
PRKCA	-0.018	0.16	-9999	-0.82	19	19
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.088	0.27	-9999	-0.76	65	65
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	-0.47	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.003	0.016	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.016	0.076	-9999	-0.53	1	1

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.009	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.01	0.15	-9999	-0.56	33	33
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.038	-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	-0.041	0.21	-9999	-0.82	33	33
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.027	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	-0.82	3	3
NF kappa B1 p50 dimer	0.02	0.029	-9999	-0.63	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.023	0.029	-9999	-0.63	1	1
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.038	-9999	-0.27	6	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.047	0.038	-9999	-0.4	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
PI3K	-0.004	0.048	-9999	-0.63	3	3
NF kappa B1 p50/RelA	0.031	0.038	-9999	-0.27	6	6
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	0.045	0.036	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.01	0.15	-9999	-0.56	33	33
LCK	-0.01	0.11	-9999	-0.42	27	27
BCL3	0.013	0.015	-9999	-0.31	1	1

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.05	0.11	-9999	-10000	0	0
CRKL	0.037	0.049	-9999	-0.46	2	2
mol:DAG	0.04	0.052	-9999	-0.37	1	1
HRAS	0.061	0.045	-9999	-0.42	1	1
MAPK8	0.019	0.091	-9999	-0.56	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	0.053	-9999	-0.38	1	1
EPOR/TRPC2/IP3 Receptors	0.009	0.047	-9999	-0.32	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.021	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	0.04	0.079	-9999	-0.37	1	1
STAT5B	0.042	0.067	-9999	-0.38	1	1
cell proliferation	0.026	0.086	-9999	-0.52	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	-0.025	0.17	-9999	-0.8	24	24
STAT1 (dimer)	0.04	0.078	-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	-0.51	1	1
elevation of cytosolic calcium ion concentration	0.009	0.047	-9999	-0.32	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.028	0.036	-9999	-10000	0	0
mol:IP3	0.04	0.052	-9999	-0.37	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.011	0.036	-9999	-0.48	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	0.065	-9999	-0.3	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	0.047	-9999	-0.32	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	0.067	-9999	-0.38	1	1
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.051	0.1	-9999	-0.41	1	1
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.012	0.037	-9999	-0.82	1	1
BTK	0.021	0.088	-9999	-0.49	9	9
BCL2	-0.001	0.28	-9999	-0.98	38	38

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.82	4	4
ITGA4	0.003	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	-0.82	3	3
PI3K	-0.004	0.048	-10000	0	-0.63	3	3
ARF6	0.013	0	-10000	0	-10000	0	0
TLN1	0.013	0	-10000	0	-10000	0	0
PXN	0.024	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.034	-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	-0.52	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	0.088	-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	0.066	-10000	0	-0.62	5	5

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.66	16	16
AKT1	0.084	0.089	-9999	-0.6	7	7
PTK2B	0.036	0.13	-9999	-0.83	6	6
VEGFR2 homodimer/Frs2	0.03	0.095	-9999	-1	4	4
CAV1	-0.008	0.13	-9999	-0.82	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	-0.61	5	5
mol:Ca2+	0.05	0.1	-9999	-0.73	7	7
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.01	0.098	-9999	-0.82	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	-0.82	3	3
HRAS/GDP	-0.009	0.081	-9999	-0.74	5	5
SH2D2A	-0.035	0.18	-9999	-0.82	23	23
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.008	0.068	-9999	-0.69	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.036	0.14	-9999	-0.56	29	29
VEGFR1 homodimer	0.012	0.037	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.01	0.094	-9999	-0.93	4	4
GRB10	0.05	0.1	-9999	-0.95	4	4
PTPN11	0.012	0.037	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.009	0.094	-9999	-0.96	4	4
HRAS	0.012	0.021	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.076	-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	-0.009	0.094	-9999	-0.79	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.003	0.09	-9999	-0.82	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	0.086	-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	-0.82	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	0.062	-9999	-0.58	4	4
mol:L-citrulline	0.076	0.066	-9999	-0.56	4	4
ITGAV	0.01	0.052	-9999	-0.82	2	2
PIK3CA	0.008	0.064	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.01	0.098	-9999	-1	4	4
VEGFR2 homodimer/VEGFA homodimer	-0.012	0.12	-9999	-0.85	7	7
VEGFR2/3 heterodimer	0.024	0.13	-9999	-1	7	7
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.052	0.11	-9999	-0.77	7	7
VEGFR2 homodimer	0.029	0.1	-9999	-1.1	4	4
FLT1	0.012	0.037	-9999	-0.82	1	1
NEDD4	0.013	0.052	-9999	-0.81	2	2
MAPK3	0.045	0.1	-9999	-0.8	5	5
MAPK1	0.045	0.1	-9999	-0.73	6	6
VEGFA145/NRP2	-0.02	0.072	-9999	-0.62	3	3
VEGFR1/2 heterodimer	0.029	0.11	-9999	-1.1	4	4
KDR	0.029	0.1	-9999	-1.1	4	4
VEGFA165/NRP1/VEGFR2 homodimer	-0.018	0.11	-9999	-1.1	4	4
SRC	0.013	0.015	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.047	0.11	-9999	-0.83	5	5
PI3K	-0.011	0.093	-9999	-0.9	4	4
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.01	0.1	-9999	-0.86	6	6
FES	0.05	0.11	-9999	-0.78	7	7
GAB1	-0.01	0.092	-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	0.069	0.091	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.01	0.1	-9999	-0.86	6	6
PI3K/GAB1	0.086	0.084	-9999	-0.61	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.009	0.094	-9999	-0.96	4	4
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	-0.78	7	7
actin cytoskeleton reorganization	-0.035	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	0.087	-9999	-0.88	4	4
MAP2K3	0.049	0.12	-9999	-0.98	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.011	0.11	-9999	-1.1	4	4
PLCG1	0.05	0.11	-9999	-0.78	7	7
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.01	0.098	-9999	-0.82	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	0.11	-9999	-0.92	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.01	0.1	-9999	-0.86	6	6
cell migration	0.083	0.095	-9999	-0.69	4	4
mol:PI-3-4-5-P3	-0.01	0.081	-9999	-0.78	4	4
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	0.047	0.095	-9999	-0.89	4	4
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	-1.1	4	4
VHL	0.008	0.064	-9999	-0.82	3	3
ITGB3	-0.011	0.14	-9999	-0.82	15	15
NOS3	0.078	0.075	-9999	-0.66	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	-0.54	21	21
PRKCB	0.04	0.11	-9999	-0.88	4	4
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	0.11	-9999	-0.92	6	6
VEGFA165/NRP2	-0.02	0.072	-9999	-0.62	3	3
MAPKKK cascade	-0.009	0.08	-9999	-0.79	4	4
NRP2	-0.014	0.091	-9999	-10000	0	0
VEGFC homodimer	0.012	0.037	-9999	-0.82	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	0.041	0.14	-9999	-0.6	16	16
PDPK1	0.076	0.09	-9999	-0.71	5	5

×

E-cadherin signaling in the nascent adherens junction

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
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	0.074	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	0.058	0.006	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.052	0.006	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.026	0.11	-9999	-0.63	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	-0.079	0.072	-9999	-0.5	1	1
PI3K	-0.002	0.021	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.17	0.16	-9999	-0.32	282	282
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	-0.52	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	0.033	-9999	-10000	0	0
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	-10000	0	0
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	-0.82	3	3
Rac1/GTP	-0.018	0.034	-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

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.009	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	0.075	-9999	-0.28	17	17
WEE1	0.022	0.011	-9999	-10000	0	0
cytokinesis	0.003	0.072	-9999	-0.3	6	6
PP2A-alpha B56	0.005	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	-0.009	0.082	-9999	-0.31	34	34
FBXW11	0.013	0	-9999	-10000	0	0
CLSPN	0.005	0.035	-9999	-0.35	2	2
GORASP1	0.013	0	-9999	-10000	0	0
metaphase	0.001	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.009	0.007	-9999	-0.066	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.013	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-9999	-10000	0	0
spindle elongation	0.017	0.012	-9999	-10000	0	0
ODF2	0.013	0.001	-9999	-10000	0	0
BUB1	-0.027	0.067	-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	0.071	-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	-0.4	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.027	0.11	-9999	-0.31	62	62
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	-0.076	3	3
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	0.058	-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	-0.32	2	2
microtubule-based process	-0.001	0.061	-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	-10000	0	0
PPP2R1A	0.013	0	-9999	-10000	0	0
chromosome segregation	0.002	0.022	-9999	-10000	0	0
PRC1	0.013	0	-9999	-10000	0	0
ECT2	0.022	0.038	-9999	-0.56	2	2
C13orf34	0.019	0.039	-9999	-0.48	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	-0.002	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	2	2
INCENP	0.009	0.053	-9999	-0.82	2	2

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.03	-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	-0.45	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.039	0.016	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.023	-10000	0	-0.43	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.012	0.037	-10000	0	-0.82	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	-0.053	0.2	-10000	0	-0.55	69	69
MAP3K5	0.012	0.037	-10000	0	-0.82	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	-0.31	1	1
AKT2/p21CIP1	-0.004	0.028	-10000	0	-0.41	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.039	0.016	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.015	-10000	0	-10000	0	0
mTORC2	-0.001	0.023	-10000	0	-0.51	1	1
AKT2	0.016	0.029	-10000	0	-0.45	2	2
FOXO1-3a-4/14-3-3 family	0.024	0.042	-10000	0	-10000	0	0
PDPK1	0.01	0.052	-10000	0	-0.82	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	0.046	0.015	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.011	-10000	0	-10000	0	0
glucose import	-0.061	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	-0.062	0.21	-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	-0.82	15	15
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

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.011	0.054	0.38	1	-10000	0	1
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	-0.016	0.15	-10000	0	-0.7	21	21
RhoA/GTP	-0.012	0.055	-10000	0	-0.39	1	1
negative regulation of cAMP metabolic process	0.022	0.069	-10000	0	-0.33	17	17
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	0.007	0.053	-10000	0	-0.38	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.07	-10000	0	-0.33	17	17
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	-0.82	1	1

×

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	-0.7	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	0.071	-10000	0	-1.6	1	1
ADORA2A	0.18	0.15	-10000	0	-0.86	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	-0.002	0.076	-10000	0	-0.96	2	2
ETS1	0.03	0.003	-10000	0	-10000	0	0
CITED2	-0.092	0.32	-10000	0	-1.2	39	39
KDR	-0.009	0.12	-10000	0	-1.4	4	4
PGK1	0.19	0.15	-10000	0	-0.89	2	2
SIRT1	0.012	0.037	-10000	0	-0.82	1	1
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.2	0.17	-10000	0	-1.2	2	2
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	-0.86	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	-0.003	0.14	-10000	0	-0.47	32	32
EGLN2	0.028	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.054	-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	-0.82	3	3
ARNT	0.027	0.011	-10000	0	-10000	0	0
SLC2A1	0.18	0.14	-10000	0	-0.86	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	0.068	-10000	0	-0.76	2	2
VEGFA	0.18	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	-0.48	12	12
CCND1	0.017	0.034	-9999	-0.25	1	1
p38 gamma/SNTA1	0.025	0.074	-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	0.078	-9999	-0.47	12	12
MAP2K6	0.013	0.084	-9999	-0.52	12	12
MAPT	0.024	0.044	-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	-0.001	0.03	-9999	-0.63	1	1
PDGFB-D/PDGFRB/APS/CBL	-0.002	0.035	-9999	-0.54	2	2
AKT1	0.059	0.043	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.023	0.05	-9999	-0.78	1	1
PIK3CA	0.008	0.064	-9999	-0.82	3	3
FGR	0.002	0.028	-9999	-0.56	1	1
mol:Ca2+	0.02	0.048	-9999	-0.82	1	1
MYC	0.018	0.15	-9999	-0.84	14	14
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	-0.82	1	1
GO:0007205	0.02	0.049	-9999	-0.84	1	1
PTEN	0.012	0.037	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.041	0.12	-9999	-0.31	84	84
PDGFB-D/PDGFRB/SHP2	-0.002	0.04	-9999	-0.63	2	2
PDGFB-D/PDGFRB/GRB10	-0.001	0.028	-9999	-0.63	1	1
cell cycle arrest	-0.002	0.029	-9999	-0.63	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	0.03	-9999	-0.56	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.028	-9999	-0.63	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.002	0.047	-9999	-0.75	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	-0.32	1	1
PDGFB-D/PDGFRB/GRB7	-0.035	0.083	-9999	-0.79	1	1
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.18	0.28	-9999	-0.62	148	148
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.028	-9999	-0.63	1	1
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.016	0.07	-9999	-0.87	1	1
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.028	-9999	-0.63	1	1
LCK	-0.008	0.086	-9999	-0.73	6	6
PDGFRB	0.012	0.038	-9999	-0.83	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	0.009	0.067	-9999	-0.95	1	1
PTPN1	0.014	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.006	0.05	-9999	-0.31	12	12
cell proliferation	0.02	0.13	-9999	-0.73	14	14
SLA	0.013	0.015	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.052	0.024	-9999	-0.43	1	1
SRC	0.006	0.028	-9999	-0.56	1	1
PI3K	-0.004	0.04	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.027	0.066	-9999	-0.69	1	1
SH2B2	0.011	0.04	-9999	-0.82	1	1
PLCgamma1/SPHK1	0.024	0.052	-9999	-0.82	1	1
LYN	0.006	0.028	-9999	-0.55	1	1
LRP1	0.012	0.037	-9999	-0.82	1	1
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.021	-9999	-0.44	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	-0.002	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	-0.21	2	2
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.027	0.089	-9999	-0.54	4	4
PRKCD	0.034	0.025	-9999	-0.5	1	1
FER	0.031	0.048	-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	-0.001	0.028	-9999	-0.63	1	1
chemotaxis	0.009	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

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.016	0.15	-9999	-0.7	21	21
CDC42/GTP	-0.011	0.053	-9999	-0.32	1	1
PLCG1	0.03	0.064	-9999	-0.33	1	1
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	0.052	-9999	-0.31	1	1
S1PR5	0.007	0.053	-9999	-0.38	8	8
S1PR4	0.009	0.038	-9999	-0.31	7	7
MAPK3	0.03	0.064	-9999	-0.33	1	1
MAPK1	0.03	0.064	-9999	-0.33	1	1
S1P/S1P5/Gi	0.022	0.07	-9999	-0.33	17	17
GNAI1	0.012	0.037	-9999	-0.82	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	0.023	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

×

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	0.024	-9999	-0.55	1	1
ATM	0.012	0.037	-9999	-0.82	1	1
MAP2K3	0.025	0.057	-9999	-0.53	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	-0.67	10	10
TXN	0.009	0.006	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	-0.013	0.15	-9999	-0.82	16	16
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.028	-9999	-0.63	1	1
TAK1/TAB family	-0.001	0.013	-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	-0.47	1	1
TRAF6	0.007	0.029	-9999	-0.46	2	2
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.003	0.09	-9999	-0.82	6	6
CCM2	0.012	0.021	-9999	-0.31	2	2
CaM/Ca2+/CAMKIIB	-0.007	0.06	-9999	-0.55	6	6
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.007	0.066	-9999	-0.58	6	6
OSM/MEKK3	-0.001	0.013	-9999	-10000	0	0
TAOK1	-0.041	0.16	-9999	-0.46	62	62
TAOK2	0.017	0.021	-9999	-0.45	1	1
TAOK3	0.017	0.021	-9999	-0.45	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.012	0.037	-9999	-0.82	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.025	-9999	-0.54	1	1
GADD45/MTK1/MTK1	-0.022	0.1	-9999	-0.49	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	-0.63	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	-0.82	32	32
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.012	0.037	-9999	-0.82	1	1
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

Figure 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	-0.017	0.095	-9999	-0.31	47	47
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	-0.63	1	1
Histones	0.035	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	-0.63	5	5
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.028	-9999	-0.63	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.01	0.066	-9999	-0.54	7	7
HDAC4/ER alpha	-0.042	0.14	-9999	-0.63	23	23
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.035	0.023	-9999	-10000	0	0
cell motility	-0.005	0.053	-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	-0.82	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.046	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	-0.82	1	1
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.001	0.02	-9999	-0.46	1	1
GNG2	0.012	0.037	-9999	-0.82	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.005	0.082	-9999	-0.82	5	5
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.012	0.021	-9999	-0.31	2	2
nuclear import	0	0	-9999	-10000	0	0

×

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	0.036	-9999	-0.31	6	6
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.022	0.025	-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	0.09	-9999	-0.33	35	35
NFKBIA	0.032	0.009	-9999	-10000	0	0
CPEB1	-0.051	0.22	-9999	-0.82	39	39
AKT1	0.032	0.009	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.011	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.015	-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	-0.82	1	1
TPX2	0.001	0.069	-9999	-10000	0	0
TP53	0.032	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	-0.015	0.028	-9999	-10000	0	0
CDC25B	0.007	0.019	-9999	-10000	0	0
G2/M transition checkpoint	0.002	0.025	-9999	-0.5	1	1
mRNA polyadenylation	-0.036	0.13	-9999	-0.5	39	39
Aurora A/CPEB	-0.037	0.14	-9999	-0.5	39	39
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	-0.46	1	1
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.007	0.034	-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	-0.82	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	0.069	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.019	0.051	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.051	0.038	-10000	0	-0.44	3	3
adherens junction organization	0.04	0.037	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.052	0.059	-10000	0	-0.74	1	1
FMN1	0.02	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	0.034	-10000	0	-0.4	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.046	0.006	-10000	0	-10000	0	0
CTNND1	0.014	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.035	-10000	0	-0.48	2	2
VASP	0.047	0.011	-10000	0	-10000	0	0
ZYX	0.047	0.011	-10000	0	-10000	0	0
JUB	0.046	0.024	-10000	0	-0.43	1	1
EGFR(dimer)	0.041	0.051	-10000	0	-0.46	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	-0.82	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	-0.4	3	3
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.002	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	-0.74	1	1
establishment of polarity of embryonic epithelium	0.046	0.011	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.005	0.082	-10000	0	-0.82	5	5
CASR	0.042	0.036	-10000	0	-0.38	3	3
RhoA/GTP	-0.002	0.028	-10000	0	-0.36	3	3
AKT2	0.049	0.034	-10000	0	-0.4	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	0.045	0.036	-10000	0	-0.5	2	2
PLCG1	-0.002	0.032	-10000	0	-0.41	3	3
Rac1/GTP	-0.004	0.042	-10000	0	-0.41	5	5
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

FoxO family signaling

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
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	0.11	0.11	-9999	-0.58	4	4
KAT2B	0.025	0.01	-9999	-10000	0	0
FOXO1/SIRT1	0.009	0.038	-9999	-0.59	1	1
CAT	0.1	0.15	-9999	-1.4	3	3
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.028	0.011	-9999	-10000	0	0
FOXO1	0.042	0.016	-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	0.064	-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	0.041	0.028	-9999	-10000	0	0
FOXO1/SKP2	0.039	0.05	-9999	-0.5	4	4
mol:GDP	0.015	0.013	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.06	-9999	-0.72	1	1
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.04	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	0.034	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	0.072	-9999	-0.79	1	1
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	-0.08	0.42	-9999	-1.5	38	38
SKP2	0.007	0.074	-9999	-0.82	4	4
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.025	0.01	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.73	1	1
FOXO1-3a-4/beta catenin	-0.003	0.048	-9999	-0.42	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.049	-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	0.054	-9999	-0.47	1	1
SFN	-0.21	0.19	-9999	-0.82	15	15
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.017	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	0.12	0.1	-9999	-0.94	2	2
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	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	-0.022	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	0.079	-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	0.5	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	-0.82	1	1
Dynamin 2/GDP	0.027	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.03	0.07	-10000	0	-0.43	11	11
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

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

×

E-cadherin signaling events

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

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

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

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.001	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.014	-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	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.002	0.026	-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	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARFIP2	0	0.004	-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	0.007	-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	-0.24	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.002	0.026	-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	-0.82	1	1
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.028	-9999	-0.63	1	1
RELB	0.013	0	-9999	-10000	0	0
NFKB2	0.013	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.QD.A8IV	TCGA.MK.A84Z	TCGA.MK.A4N9	TCGA.MK.A4N7
109_MAP3K5	-0.21	0.058	-0.28	-0.018
47_PPARGC1A	0.013	0.013	-0.82	-0.82
105_BMP4	0.013	0.013	0.013	-0.31
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	-0.49	-0.49	-0.49
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.013
84_STAT5B	0.047	0	0.047	-0.097
84_STAT5A	0.047	0	0.047	-0.097