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)	169
Signaling events regulated by Ret tyrosine kinase	152
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	126
TCGA08_retinoblastoma	123
Reelin signaling pathway	116
Wnt signaling	108
IL4-mediated signaling events	104
FOXA2 and FOXA3 transcription factor networks	100
PDGFR-alpha signaling pathway	99

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Ephrin A reverse signaling	0.5110	256	1795	7	-0.52	0	1000	-1000	-0.029	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3373	169	13229	78	-0.81	0.24	1000	-1000	-0.072	-1000
Signaling events regulated by Ret tyrosine kinase	0.3034	152	12495	82	-0.46	0.013	1000	-1000	-0.084	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2515	126	8573	68	-0.9	0.37	1000	-1000	-0.1	-1000
TCGA08_retinoblastoma	0.2455	123	985	8	-0.12	0.072	1000	-1000	-0.019	-1000
Reelin signaling pathway	0.2315	116	6514	56	-0.59	0.033	1000	-1000	-0.087	-1000
Wnt signaling	0.2156	108	760	7	-0.41	0.013	1000	-1000	-0.028	-1000
IL4-mediated signaling events	0.2076	104	9509	91	-1.3	0.67	1000	-1000	-0.12	-1000
FOXA2 and FOXA3 transcription factor networks	0.1996	100	4621	46	-0.91	0.021	1000	-1000	-0.042	-1000
PDGFR-alpha signaling pathway	0.1976	99	4366	44	-0.48	0.033	1000	-1000	-0.057	-1000
Noncanonical Wnt signaling pathway	0.1876	94	2463	26	-0.41	0.013	1000	-1000	-0.085	-1000
Signaling events mediated by the Hedgehog family	0.1717	86	4510	52	-0.38	0.2	1000	-1000	-0.071	-1000
Nongenotropic Androgen signaling	0.1677	84	4406	52	-0.34	0.16	1000	-1000	-0.063	-1000
Calcium signaling in the CD4+ TCR pathway	0.1617	81	2512	31	-0.52	0.013	1000	-1000	-0.078	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1497	75	2560	34	-0.17	0.013	1000	-1000	-0.069	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1397	70	3826	54	-0.59	0.028	1000	-1000	-0.1	-1000
Glypican 1 network	0.1317	66	3189	48	-0.38	0.028	1000	-1000	-0.046	-1000
HIF-1-alpha transcription factor network	0.1297	65	4988	76	-0.57	0.041	1000	-1000	-0.081	-1000
Ephrin B reverse signaling	0.1257	63	3057	48	-0.3	0.18	1000	-1000	-0.067	-1000
Endothelins	0.1257	63	6102	96	-0.39	0.013	1000	-1000	-0.084	-1000
Glucocorticoid receptor regulatory network	0.1218	61	6974	114	-0.56	0.36	1000	-1000	-0.065	-1000
IL23-mediated signaling events	0.1158	58	3524	60	-0.31	0.019	1000	-1000	-0.14	-1000
TCR signaling in naïve CD8+ T cells	0.1078	54	5094	93	-0.2	0.088	1000	-1000	-0.078	-1000
IGF1 pathway	0.1078	54	3116	57	-0.19	0.058	1000	-1000	-0.11	-1000
Glypican 2 network	0.1058	53	212	4	-0.087	-0.009	1000	-1000	-0.035	-1000
BMP receptor signaling	0.1018	51	4187	81	-0.57	0.026	1000	-1000	-0.089	-1000
Arf6 signaling events	0.0998	50	3123	62	-0.32	0.02	1000	-1000	-0.065	-1000
Coregulation of Androgen receptor activity	0.0978	49	3790	76	-0.78	0.062	1000	-1000	-0.046	-1000
Syndecan-1-mediated signaling events	0.0958	48	1655	34	-0.2	0.013	1000	-1000	-0.056	-1000
EPHB forward signaling	0.0878	44	3824	85	-0.3	0.15	1000	-1000	-0.087	-1000
Syndecan-4-mediated signaling events	0.0818	41	2774	67	-0.26	0.023	1000	-1000	-0.089	-1000
IL12-mediated signaling events	0.0798	40	3560	87	-0.4	0.026	1000	-1000	-0.11	-1000
IL6-mediated signaling events	0.0798	40	3008	75	-0.2	0.06	1000	-1000	-0.08	-1000
Hedgehog signaling events mediated by Gli proteins	0.0778	39	2563	65	-0.66	0.061	1000	-1000	-0.058	-1000
amb2 Integrin signaling	0.0778	39	3233	82	-0.24	0.013	1000	-1000	-0.081	-1000
Signaling mediated by p38-alpha and p38-beta	0.0699	35	1551	44	-0.23	0.013	1000	-1000	-0.058	-1000
EGFR-dependent Endothelin signaling events	0.0679	34	727	21	-0.11	0.013	1000	-1000	-0.065	-1000
Osteopontin-mediated events	0.0639	32	1244	38	-0.26	0.013	1000	-1000	-0.099	-1000
Thromboxane A2 receptor signaling	0.0639	32	3373	105	-0.22	0.034	1000	-1000	-0.068	-1000
Ras signaling in the CD4+ TCR pathway	0.0639	32	553	17	-0.088	0.013	1000	-1000	-0.042	-1000
FAS signaling pathway (CD95)	0.0619	31	1495	47	-0.23	0.031	1000	-1000	-0.052	-1000
IL27-mediated signaling events	0.0619	31	1583	51	-0.15	0.067	1000	-1000	-0.07	-1000
Plasma membrane estrogen receptor signaling	0.0599	30	2599	86	-0.18	0.021	1000	-1000	-0.074	-1000
Regulation of Androgen receptor activity	0.0559	28	1981	70	-0.48	0.034	1000	-1000	-0.059	-1000
Visual signal transduction: Rods	0.0539	27	1432	52	-0.2	0.013	1000	-1000	-0.072	-1000
Syndecan-2-mediated signaling events	0.0519	26	1811	69	-0.22	0.038	1000	-1000	-0.056	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0519	26	1365	52	-0.28	0.054	1000	-1000	-0.054	-1000
Regulation of p38-alpha and p38-beta	0.0519	26	1456	54	-0.47	0.013	1000	-1000	-0.06	-1000
ErbB2/ErbB3 signaling events	0.0479	24	1581	65	-0.12	0.027	1000	-1000	-0.064	-1000
Integrins in angiogenesis	0.0479	24	2030	84	-0.23	0.034	1000	-1000	-0.085	-1000
LPA receptor mediated events	0.0479	24	2455	102	-0.25	0.031	1000	-1000	-0.082	-1000
BCR signaling pathway	0.0479	24	2462	99	-0.2	0.023	1000	-1000	-0.098	-1000
JNK signaling in the CD4+ TCR pathway	0.0459	23	391	17	-0.1	0.019	1000	-1000	-0.062	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0459	23	2014	85	-0.27	0.013	1000	-1000	-0.08	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0459	23	2088	88	-0.32	0.03	1000	-1000	-0.1	-1000
Signaling events mediated by PTP1B	0.0439	22	1697	76	-0.25	0.021	1000	-1000	-0.079	-1000
p75(NTR)-mediated signaling	0.0439	22	2756	125	-0.36	0.067	1000	-1000	-0.096	-1000
Nectin adhesion pathway	0.0419	21	1350	63	-0.26	0.03	1000	-1000	-0.075	-1000
Effects of Botulinum toxin	0.0419	21	552	26	-0.16	0.019	1000	-1000	-0.06	-1000
Regulation of nuclear SMAD2/3 signaling	0.0399	20	2728	136	-0.34	0.064	1000	-1000	-0.073	-1000
Aurora C signaling	0.0399	20	146	7	-0.061	0	1000	-1000	-0.036	-1000
Visual signal transduction: Cones	0.0379	19	728	38	-0.088	0.013	1000	-1000	-0.057	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0379	19	2307	120	-0.31	0.042	1000	-1000	-0.075	-1000
ErbB4 signaling events	0.0359	18	1274	69	-0.14	0.058	1000	-1000	-0.081	-1000
IL1-mediated signaling events	0.0359	18	1153	62	-0.12	0.066	1000	-1000	-0.097	-1000
Signaling events mediated by PRL	0.0359	18	617	34	-0.11	0.013	1000	-1000	-0.039	-1000
FOXM1 transcription factor network	0.0359	18	919	51	-0.17	0.053	1000	-1000	-0.16	-1000
Aurora B signaling	0.0359	18	1212	67	-0.38	0.014	1000	-1000	-0.062	-1000
Fc-epsilon receptor I signaling in mast cells	0.0339	17	1665	97	-0.2	0.03	1000	-1000	-0.094	-1000
Insulin-mediated glucose transport	0.0339	17	552	32	-0.21	0.042	1000	-1000	-0.062	-1000
TCGA08_rtk_signaling	0.0339	17	459	26	-0.24	0.025	1000	-1000	-0.022	-1000
LPA4-mediated signaling events	0.0299	15	189	12	-0.12	0.015	1000	-1000	-0.023	-1000
Presenilin action in Notch and Wnt signaling	0.0299	15	942	61	-0.2	0.042	1000	-1000	-0.073	-1000
Syndecan-3-mediated signaling events	0.0299	15	535	35	-0.16	0.013	1000	-1000	-0.073	-1000
IL2 signaling events mediated by STAT5	0.0299	15	347	22	-0.067	0.039	1000	-1000	-0.054	-1000
Insulin Pathway	0.0299	15	1123	74	-0.084	0.035	1000	-1000	-0.089	-1000
Rapid glucocorticoid signaling	0.0299	15	308	20	-0.094	0.015	1000	-1000	-0.037	-1000
IFN-gamma pathway	0.0279	14	999	68	-0.11	0.041	1000	-1000	-0.092	-1000
Signaling events mediated by HDAC Class III	0.0279	14	566	40	-0.36	0.024	1000	-1000	-0.043	-1000
VEGFR1 specific signals	0.0279	14	791	56	-0.071	0.041	1000	-1000	-0.083	-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	-0.009	-1000
a4b1 and a4b7 Integrin signaling	0.0259	13	68	5	-0.033	0.003	1000	-1000	-0.038	-1000
Ceramide signaling pathway	0.0259	13	1038	76	-0.18	0.024	1000	-1000	-0.065	-1000
IL2 signaling events mediated by PI3K	0.0259	13	786	58	-0.066	0.031	1000	-1000	-0.082	-1000
BARD1 signaling events	0.0220	11	631	57	-0.035	0.052	1000	-1000	-0.07	-1000
Cellular roles of Anthrax toxin	0.0220	11	435	39	-0.088	0.019	1000	-1000	-0.032	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0220	11	519	45	-0.088	0.039	1000	-1000	-0.085	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0220	11	825	74	-0.18	0.085	1000	-1000	-0.09	-1000
Regulation of Telomerase	0.0220	11	1193	102	-0.28	0.052	1000	-1000	-0.093	-1000
Caspase cascade in apoptosis	0.0200	10	797	74	-0.088	0.028	1000	-1000	-0.051	-1000
mTOR signaling pathway	0.0200	10	532	53	-0.046	0.021	1000	-1000	-0.06	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0200	10	885	83	-0.21	0.052	1000	-1000	-0.075	-1000
Class I PI3K signaling events	0.0200	10	794	73	-0.25	0.032	1000	-1000	-0.071	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0180	9	258	28	-0.18	0.031	1000	-1000	-0.055	-1000
Retinoic acid receptors-mediated signaling	0.0180	9	573	58	-0.11	0.034	1000	-1000	-0.071	-1000
S1P3 pathway	0.0180	9	400	42	-0.18	0.049	1000	-1000	-0.053	-1000
Class I PI3K signaling events mediated by Akt	0.0160	8	568	68	-0.21	0.052	1000	-1000	-0.063	-1000
TRAIL signaling pathway	0.0160	8	399	48	-0.075	0.047	1000	-1000	-0.067	-1000
ceramide signaling pathway	0.0160	8	429	49	-0.088	0.031	1000	-1000	-0.048	-1000
S1P1 pathway	0.0140	7	276	36	-0.028	0.033	1000	-1000	-0.052	-1000
Canonical Wnt signaling pathway	0.0140	7	379	51	-0.048	0.067	1000	-1000	-0.057	-1000
Arf6 downstream pathway	0.0120	6	290	43	-0.17	0.093	1000	-1000	-0.038	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0120	6	227	37	-0.035	0.04	1000	-1000	-0.058	-1000
FoxO family signaling	0.0120	6	428	64	-0.21	0.16	1000	-1000	-0.06	-1000
Canonical NF-kappaB pathway	0.0100	5	226	39	-0.088	0.073	1000	-1000	-0.082	-1000
S1P5 pathway	0.0100	5	99	17	-0.016	0.022	1000	-1000	-0.048	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0100	5	668	125	-0.036	0.086	1000	-1000	-0.093	-1000
E-cadherin signaling in the nascent adherens junction	0.0100	5	399	76	-0.17	0.074	1000	-1000	-0.086	-1000
Circadian rhythm pathway	0.0080	4	106	22	-0.057	0.013	1000	-1000	-0.059	-1000
EPO signaling pathway	0.0080	4	243	55	-0.025	0.061	1000	-1000	-0.091	-1000
Signaling events mediated by HDAC Class I	0.0080	4	503	104	-0.088	0.059	1000	-1000	-0.072	-1000
Atypical NF-kappaB pathway	0.0080	4	148	31	-0.041	0.047	1000	-1000	-0.047	-1000
HIF-2-alpha transcription factor network	0.0060	3	136	43	-0.2	0.2	1000	-1000	-0.077	-1000
Signaling mediated by p38-gamma and p38-delta	0.0060	3	53	15	0	0.031	1000	-1000	-0.029	-1000
Paxillin-dependent events mediated by a4b1	0.0060	3	143	36	-0.033	0.024	1000	-1000	-0.078	-1000
PDGFR-beta signaling pathway	0.0060	3	378	97	-0.18	0.064	1000	-1000	-0.089	-1000
S1P4 pathway	0.0060	3	86	25	-0.016	0.032	1000	-1000	-0.053	-1000
p38 MAPK signaling pathway	0.0060	3	154	44	-0.041	0.025	1000	-1000	-0.069	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0040	2	67	23	-0.04	0.049	1000	-1000	-0.078	-1000
Signaling events mediated by HDAC Class II	0.0040	2	178	75	-0.046	0.035	1000	-1000	-0.057	-1000
PLK2 and PLK4 events	0.0040	2	6	3	0.009	0.022	1000	-1000	-0.02	-1000
Aurora A signaling	0.0040	2	167	60	-0.051	0.038	1000	-1000	-0.063	-1000
PLK1 signaling events	0.0040	2	246	85	-0.035	0.033	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0040	2	125	43	-0.004	0.052	1000	-1000	-0.066	-1000
Arf6 trafficking events	0.0020	1	83	71	-0.022	0.046	1000	-1000	-0.076	-1000
TCGA08_p53	0.0000	0	0	7	-0.081	0.052	1000	-1000	-0.013	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.059	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.045	-1000
Arf1 pathway	0.0000	0	37	54	-0.006	0.035	1000	-1000	-0.048	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.064	-1000
Total	NA	4125	228699	7203	-29	-990	131000	-131000	-8.8	-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	293	293
CRKL	-0.22	0.24	-10000	0	-0.42	288	288
HRAS	-0.19	0.21	-10000	0	-0.5	48	48
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	-0.44	28	28
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	288	288
HRAS/SPRED1	-0.18	0.14	-10000	0	-0.39	47	47
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	-0.4	43	43
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	-0.75	38	38
JAK2	-0.52	0.45	-10000	0	-0.9	288	288
STAT1 (dimer)	-0.59	0.57	-10000	0	-1.1	288	288
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.25	0.21	-10000	0	-0.42	291	291
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	-0.48	77	77
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	288	288
KITLG	-0.005	0.11	-10000	0	-0.85	8	8
cell motility	-0.42	0.42	-10000	0	-0.77	288	288
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	-0.64	288	288
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	-0.66	288	288
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	-0.66	133	133
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	-0.41	308	308
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	-0.38	283	283
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

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.041	0.16	-10000	0	-0.5	39	39
NFATC2	-0.24	0.38	-10000	0	-0.81	131	131
NFATC3	-0.084	0.13	-10000	0	-0.31	26	26
CD40LG	-0.74	0.57	-10000	0	-1.2	300	300
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	-1.1	177	177
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	-0.92	124	124
Jun/NFAT1-c-4/p21SNFT	-0.66	0.6	-10000	0	-1.2	260	260
AP-1/NFAT1-c-4	-0.9	0.78	-10000	0	-1.5	287	287
IKZF1	-0.18	0.34	-10000	0	-0.78	89	89
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.86	116	116
AP-1/NFAT1	-0.42	0.48	-10000	0	-0.9	218	218
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.84	-10000	0	-1.6	241	241
EGR3	-0.56	0.72	-10000	0	-1.2	208	208
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	104	104
FOSL1	-0.033	0.12	-10000	0	-0.32	69	69
NFAT1-c-4/MAF/IRF4	-0.56	0.56	-10000	0	-1	257	257
DGKA	-0.16	0.3	-10000	0	-0.67	101	101
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.55	0.56	-10000	0	-1	256	256
CTLA4	-0.24	0.39	-10000	0	-0.82	122	122
NFAT1-c-4 (dimer)/EGR1	-0.64	0.66	-10000	0	-1.2	257	257
NFAT1-c-4 (dimer)/EGR4	-0.58	0.56	-10000	0	-1.1	257	257
FOS	-0.21	0.36	-10000	0	-0.82	128	128
IFNG	-0.43	0.54	-10000	0	-1.1	168	168
T cell activation	-0.44	0.42	-10000	0	-0.96	167	167
MAF	0.013	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.37	0.42	0.75	236	-10000	0	236
TNF	-0.6	0.57	-10000	0	-1.1	272	272
FASLG	-0.75	0.78	-10000	0	-1.4	254	254
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	-0.74	74	74
NFAT1-c-4/ICER1	-0.55	0.55	-10000	0	-1	253	253
GATA3	-0.03	0.18	-10000	0	-0.78	28	28
T-helper 1 cell differentiation	-0.41	0.52	-10000	0	-1	171	171
IL2RA	-0.49	0.46	-10000	0	-1	174	174
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.3	-10000	0	-0.7	88	88
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	-1.1	281	281
CSF2	-0.78	0.53	-10000	0	-1.2	297	297
JunB/Fra1/NFAT1-c-4	-0.54	0.53	-10000	0	-1	253	253
IL4	-0.33	0.37	-10000	0	-0.93	112	112
IL5	-0.7	0.54	-10000	0	-1.1	283	283
IL2	-0.45	0.44	-10000	0	-1	161	161
IL3	-0.097	0.062	-10000	0	-10000	0	0
RNF128	0.049	0.041	-10000	0	-0.87	1	1
NFATC1	-0.37	0.42	-10000	0	-0.75	236	236
CDK4	0.22	0.24	0.58	84	-10000	0	84
PTPRK	-0.16	0.3	-10000	0	-0.7	85	85
IL8	-0.72	0.54	-10000	0	-1.1	281	281
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	206	206
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	0.22	2	-10000	0	2
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 S6. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.82	36	36
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	-0.9	29	29
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	-0.33	20	20
neuron migration	-0.3	0.22	-9999	-0.66	30	30
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

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.28	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

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.6	0.44	-10000	0	-1.1	171	171
STAT6 (cleaved dimer)	-0.66	0.44	-10000	0	-1	267	267
IGHG1	-0.21	0.14	-10000	0	-0.36	57	57
IGHG3	-0.59	0.42	-10000	0	-0.94	246	246
AKT1	-0.32	0.26	-10000	0	-0.71	81	81
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.25	-10000	0	-0.73	62	62
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.71	122	122
THY1	-0.6	0.44	-10000	0	-1.1	167	167
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	-0.69	207	207
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.69	84	84
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	260	260
SOCS1	-0.41	0.29	-10000	0	-0.72	148	148
SOCS3	-0.37	0.34	-10000	0	-0.98	71	71
FCER2	-0.63	0.47	-10000	0	-0.98	266	266
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.67	0.47	-10000	0	-1.1	231	231
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.65	54	54
T cell proliferation	-0.61	0.46	-10000	0	-1.1	200	200
IL4R/JAK1	-0.6	0.44	-10000	0	-1	192	192
EGR2	-0.96	0.72	-10000	0	-1.6	261	261
JAK2	-0.02	0.058	-10000	0	-0.85	2	2
JAK3	-0.066	0.14	-10000	0	-0.31	120	120
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.008	-10000	0	-10000	0	0
COL1A2	-0.2	0.17	-10000	0	-0.58	30	30
CCL26	-0.62	0.45	-10000	0	-1.1	176	176
IL4R	-0.64	0.46	-10000	0	-1.1	200	200
PTPN6	0.029	0.009	-10000	0	-10000	0	0
IL13RA2	-0.71	0.56	-10000	0	-1.3	200	200
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.35	0.5	-10000	0	-1.2	107	107
ARG1	-0.15	0.12	-10000	0	-10000	0	0
CBL	-0.39	0.29	-10000	0	-0.69	170	170
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	101	101
CD40LG	-0.13	0.31	-10000	0	-0.8	88	88
MAPK14	-0.39	0.31	-10000	0	-0.77	134	134
mitosis	-0.31	0.24	-10000	0	-0.66	83	83
STAT6	-0.68	0.51	-10000	0	-1.1	238	238
SPI1	0	0.074	-10000	0	-0.31	27	27
RPS6KB1	-0.29	0.23	-10000	0	-0.66	67	67
STAT6 (dimer)	-0.68	0.51	-10000	0	-1.1	238	238
STAT6 (dimer)/PARP14	-0.64	0.47	-10000	0	-1.1	233	233
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	-0.71	93	93
FRAP1	-0.32	0.26	-10000	0	-0.71	81	81
LTA	-0.62	0.45	-10000	0	-1.1	204	204
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.67	0.49	1.1	239	-10000	0	239
CCL11	-0.59	0.43	-10000	0	-1.1	178	178
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.7	90	90
IL2RG	-0.044	0.19	-10000	0	-0.52	57	57
IL10	-0.62	0.47	-10000	0	-1.1	184	184
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	199	199
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.49	0.33	-10000	0	-0.8	215	215
COL1A1	-0.26	0.23	-10000	0	-0.75	29	29
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	161	161
IL2R gamma/JAK3	-0.081	0.18	-10000	0	-0.5	57	57
TFF3	-1.3	0.61	-10000	0	-1.6	408	408
ALOX15	-0.61	0.44	-10000	0	-1.1	167	167
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.52	0.36	-10000	0	-0.84	231	231
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	-0.66	86	86
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.71	81	81
PI3K	-0.34	0.28	-10000	0	-0.76	80	80
DOK2	-0.001	0.079	-10000	0	-0.37	19	19
ETS1	0.03	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.25	0.21	-10000	0	-0.63	56	56
ITGB3	-0.62	0.47	-10000	0	-1.1	182	182
PIGR	-0.65	0.5	-10000	0	-1.2	185	185
IGHE	0.052	0.035	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.61	57	57
BCL6	0.012	0.037	-10000	0	-0.82	1	1
OPRM1	-0.61	0.44	-10000	0	-1.1	167	167
RETNLB	-0.61	0.44	-10000	0	-1.1	173	173
SELP	-0.61	0.45	-10000	0	-1.1	181	181
AICDA	-0.59	0.42	-10000	0	-1	180	180

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.51	0.54	-9999	-1	222	222
PCK1	-0.34	0.49	-9999	-1.5	63	63
HNF4A	-0.66	0.66	-9999	-1.3	252	252
KCNJ11	-0.48	0.54	-9999	-1	206	206
AKT1	-0.042	0.12	-9999	-0.38	15	15
response to starvation	-0.017	0.033	-9999	-10000	0	0
DLK1	-0.49	0.54	-9999	-1.1	198	198
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.51	0.54	-9999	-1.1	207	207
TAT	-0.2	0.22	-9999	-0.58	34	34
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	-0.74	32	32
PKLR	-0.52	0.54	-9999	-1	220	220
APOA1	-0.91	0.89	-9999	-1.7	256	256
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	-0.72	55	55
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	215	215
HMGCS1	-0.51	0.54	-9999	-1.1	212	212
NR3C1	0.019	0.018	-9999	-10000	0	0
CPT1B	-0.51	0.54	-9999	-1	218	218
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.66	0.7	-9999	-1.3	243	243
CREB1	0.001	0.052	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.56	12	12
PDX1	-0.18	0.21	-9999	-0.61	1	1
UCP2	-0.51	0.54	-9999	-1	219	219
ALDOB	-0.48	0.54	-9999	-1	205	205
AFP	-0.046	0.11	-9999	-0.45	17	17
BDH1	-0.51	0.54	-9999	-1	217	217
HADH	-0.48	0.54	-9999	-1.1	182	182
F2	-0.62	0.63	-9999	-1.2	241	241
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.006	0.09	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.7	2	2
INS	-0.012	0.066	-9999	-0.83	3	3
FOXA1	-0.055	0.14	-9999	-0.52	15	15
FOXA3	-0.073	0.17	-9999	-0.36	100	100
FOXA2	-0.55	0.61	-9999	-1.1	226	226
ABCC8	-0.78	0.75	-9999	-1.4	276	276
ALB	-0.096	0.32	-9999	-1.3	30	30

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.25	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

×

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	-0.6	122	122
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	-0.48	134	134
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

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.11	0.26	-10000	0	-0.68	36	36
IHH	-0.2	0.36	-10000	0	-0.83	124	124
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	-0.48	127	127
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	128	128
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	128	128
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	128	128
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	128	128
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	-0.5	128	128
SMO/Vitamin D3	-0.09	0.22	-10000	0	-0.44	127	127
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	-0.43	86	86
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	128	128
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	128	128
HHIP	-0.31	0.4	-10000	0	-0.81	197	197

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.21	0.25	-10000	0	-0.5	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	-0.62	210	210
cell proliferation	-0.19	0.28	-10000	0	-0.68	79	79
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	-0.59	87	87
MAPK1	-0.081	0.13	-10000	0	-0.31	77	77
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	0.53	128	-10000	0	128
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	128	128
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

×

Calcium signaling in the CD4+ TCR pathway

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
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	-0.86	213	213
PTGS2	-0.41	0.39	-9999	-0.85	189	189
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	-0.58	178	178
FOS	-0.2	0.36	-9999	-0.82	128	128
IFNG	-0.44	0.41	-9999	-0.84	214	214
AP-1/NFAT1-c-4	-0.52	0.52	-9999	-0.96	241	241
FASLG	-0.42	0.39	-9999	-0.84	195	195
NFAT1-c-4/ICER1	-0.12	0.2	-9999	-0.5	95	95
IL2RA	-0.41	0.38	-9999	-0.83	189	189
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.36	-9999	-0.76	270	270
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.5	101	101
IL4	-0.39	0.36	-9999	-0.8	186	186
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 S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	91	91
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

×

Lissencephaly gene (LIS1) in neuronal migration and development

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	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	-0.72	17	17
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	-0.36	195	195
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.3	0.22	-9999	-0.79	17	17
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

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.001	0.025	-10000	0	-0.54	1	1
fibroblast growth factor receptor signaling pathway	-0.001	0.025	-10000	0	-0.54	1	1
LAMA1	-0.049	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

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.19	0.42	-9999	-0.9	71	71
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.29	0.34	-9999	-0.81	116	116
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.19	0.42	-9999	-0.91	71	71
AP1	-0.28	0.45	-9999	-0.92	152	152
ABCG2	-0.2	0.43	-9999	-0.92	72	72
HIF1A	-0.01	0.068	-9999	-10000	0	0
TFF3	-0.57	0.51	-9999	-1	219	219
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	23	23
MCL1	-0.19	0.42	-9999	-0.9	71	71
NDRG1	-0.19	0.42	-9999	-0.9	71	71
SERPINE1	-0.2	0.43	-9999	-0.91	77	77
FECH	-0.19	0.42	-9999	-0.9	71	71
FURIN	-0.19	0.42	-9999	-0.9	71	71
NCOA2	-0.065	0.24	-9999	-0.82	48	48
EP300	-0.064	0.18	-9999	-0.32	133	133
HMOX1	-0.2	0.42	-9999	-0.91	73	73
BHLHE40	-0.2	0.43	-9999	-0.92	73	73
BHLHE41	-0.19	0.42	-9999	-0.91	72	72
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	-0.92	71	71
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	-0.9	71	71
TF	-0.24	0.49	-9999	-1	94	94
CITED2	-0.22	0.47	-9999	-1	84	84
HIF1A/ARNT	-0.3	0.38	-9999	-0.98	81	81
LDHA	-0.039	0.05	-9999	-10000	0	0
ETS1	-0.19	0.42	-9999	-0.9	71	71
PGK1	-0.19	0.42	-9999	-0.9	71	71
NOS2	-0.21	0.43	-9999	-0.9	82	82
ITGB2	-0.2	0.42	-9999	-0.92	72	72
ALDOA	-0.19	0.42	-9999	-0.9	71	71
Cbp/p300/CITED2	-0.33	0.51	-9999	-1	122	122
FOS	-0.2	0.36	-9999	-0.82	128	128
HK2	-0.19	0.42	-9999	-0.91	73	73
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	-0.91	72	72
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.19	0.42	-9999	-0.9	71	71
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	78	78
VEGFA	-0.16	0.38	-9999	-0.73	88	88
HIF1A/JAB1	-0.011	0.021	-9999	-10000	0	0
CP	-0.35	0.55	-9999	-1	155	155
CXCL12	-0.24	0.48	-9999	-1	92	92
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.19	0.42	-9999	-0.9	71	71
EGLN3	-0.21	0.44	-9999	-0.93	77	77
CA9	-0.21	0.42	-9999	-0.91	75	75
TERT	-0.2	0.42	-9999	-0.91	72	72
ENO1	-0.19	0.42	-9999	-0.9	71	71
PFKL	-0.19	0.42	-9999	-0.9	71	71
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.23	0.44	-9999	-0.89	98	98
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	-0.9	73	73
SLC2A1	-0.16	0.38	-9999	-0.73	82	82
LEP	-0.2	0.42	-9999	-0.92	71	71
HIF1A/ARNT/Cbp/p300	-0.3	0.36	-9999	-0.83	121	121
EPO	-0.14	0.33	-9999	-0.91	31	31
CREBBP	-0.064	0.18	-9999	-0.32	135	135
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.8	116	116
PFKFB3	-0.19	0.42	-9999	-0.91	72	72
NT5E	-0.2	0.43	-9999	-0.92	71	71

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.054	0.14	-9999	-0.55	12	12
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.7	62	62
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	-0.54	81	81
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.086	0.18	-9999	-0.39	91	91
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	74	74
ADCY7	-0.098	0.2	-9999	-0.5	73	73
ADCY1	-0.1	0.21	-9999	-0.53	75	75
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	-0.55	102	102
ADCY9	-0.098	0.2	-9999	-0.5	73	73
arachidonic acid secretion	-0.17	0.32	-9999	-0.65	134	134
ETB receptor/Endothelin-1/Gq/GTP	-0.098	0.22	-9999	-0.43	123	123
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	-0.54	10	10
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	-0.31	7	7
mol:GDP	-0.12	0.26	-9999	-0.56	93	93
SLC9A3	-0.049	0.19	-9999	-0.81	21	21
RAF1	-0.15	0.3	-9999	-0.59	126	126
JUN	-0.28	0.51	-9999	-1.2	122	122
JAK2	-0.056	0.15	-9999	-0.57	13	13
mol:IP3	-0.11	0.23	-9999	-0.49	109	109
ETA receptor/Endothelin-1	-0.041	0.2	-9999	-0.48	39	39
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	128	128
Gai/GDP	-0.002	0.13	-9999	-0.64	17	17
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	-0.48	109	109
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	-0.57	121	121
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.45	108	108
MAPK14	-0.065	0.18	-9999	-0.48	34	34
TRPC6	-0.14	0.3	-9999	-0.75	60	60
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	-0.4	86	86
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	-0.9	134	134
MAPK1	-0.23	0.43	-9999	-0.9	134	134
Rac1/GDP	-0.1	0.24	-9999	-0.54	80	80
cAMP biosynthetic process	-0.14	0.21	-9999	-0.55	80	80
MAPK8	-0.18	0.35	-9999	-0.69	113	113
SRC	0.013	0.015	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.008	0.078	-9999	-0.33	13	13
p130Cas/CRK/Src/PYK2	-0.13	0.3	-9999	-0.61	99	99
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.54	80	80
COL1A2	-0.041	0.17	-9999	-0.64	13	13
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.49	14	14
mol:DAG	-0.11	0.23	-9999	-0.49	109	109
MAP2K2	-0.18	0.35	-9999	-0.7	136	136
MAP2K1	-0.18	0.35	-9999	-0.7	137	137
EDNRA	-0.039	0.099	-9999	-0.48	6	6
positive regulation of muscle contraction	-0.038	0.13	-9999	-0.53	9	9
Gq family/GDP	-0.19	0.29	-9999	-0.66	120	120
HRAS/GTP	-0.13	0.26	-9999	-0.57	98	98
PRKCH	-0.1	0.22	-9999	-0.5	94	94
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.25	-9999	-0.53	109	109
PRKCB	-0.12	0.23	-9999	-0.52	95	95
PRKCE	-0.11	0.24	-9999	-0.53	87	87
PRKCD	-0.1	0.22	-9999	-0.51	87	87
PRKCG	-0.11	0.23	-9999	-0.52	86	86
regulation of vascular smooth muscle contraction	-0.3	0.55	-9999	-1.2	128	128
PRKCQ	-0.11	0.23	-9999	-0.52	90	90
PLA2G4A	-0.19	0.36	-9999	-0.72	134	134
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

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.046	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	-0.78	57	57
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	0.31	79	-0.49	6	85
PRL	-0.088	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.24	0.31	0.58	167	-0.48	26	193
RELA	-0.029	0.087	-10000	0	-10000	0	0
FGG	0.24	0.19	0.51	117	-10000	0	117
GR beta/TIF2	0.08	0.24	0.33	90	-0.56	48	138
IFNG	-0.49	0.51	-10000	0	-0.92	217	217
apoptosis	0.034	0.24	0.49	70	-0.51	5	75
CREB1	0.012	0.023	-10000	0	-10000	0	0
histone acetylation	-0.069	0.17	-10000	0	-0.4	63	63
BGLAP	-0.098	0.15	-10000	0	-0.53	12	12
GR/PKAc	0.13	0.1	0.34	33	-0.41	1	34
NF kappa B1 p50/RelA	-0.061	0.16	-10000	0	-0.45	28	28
SMARCD1	0.014	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.096	0.27	99	-10000	0	99
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	-0.56	40	40
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.061	0.23	0.51	49	-0.74	5	54
CSN2	0.2	0.14	0.43	79	-10000	0	79
BRG1/BAF155/BAF170/BAF60A	0.021	0.048	-10000	0	-0.34	2	2
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	-0.34	315	315
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.044	0.16	0.3	34	-0.44	20	54
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.078	0.44	0.48	57	-0.88	108	165
JUN	-0.33	0.31	-10000	0	-0.68	183	183
IL4	-0.13	0.18	-10000	0	-0.67	22	22
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	-0.82	188	188
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.32	56	-0.47	5	61
cortisol/GR alpha (monomer)	0.36	0.3	0.68	191	-10000	0	191
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	-0.95	245	245
AFP	-0.22	0.22	-10000	0	-0.62	78	78
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.5	39	-10000	0	39
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	-0.74	247	247
KRT14	-0.24	0.18	-10000	0	-0.6	25	25
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.065	0.066	-10000	0	-10000	0	0
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	-0.96	245	245
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	-1.1	159	159
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	-0.53	26	26
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.38	191	-10000	0	191
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	-0.67	94	94
NFKB1	-0.031	0.096	-10000	0	-0.38	6	6
MAPK8	-0.19	0.21	-10000	0	-0.49	114	114
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.028	0.25	0.5	70	-0.53	5	75
BAX	0.029	0.034	-10000	0	-10000	0	0
POMC	-0.54	0.69	-10000	0	-1.4	154	154
EP300	0.066	0.066	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.33	0.24	0.59	186	-10000	0	186
proteasomal ubiquitin-dependent protein catabolic process	0.086	0.072	0.24	29	-10000	0	29
SGK1	0.1	0.22	-10000	0	-1.4	10	10
IL13	-0.3	0.25	-10000	0	-0.79	64	64
IL6	-0.37	0.52	-10000	0	-1.1	137	137
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.62	74	74
IL2	-0.36	0.27	-10000	0	-0.74	120	120
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	-0.84	72	72
CDK5R1/CDK5	0.007	0.025	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.023	0.12	-10000	0	-0.63	2	2
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.55	178	-10000	0	178
SMARCA4	0.014	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.4	124	-0.39	1	125
NF kappa B1 p50/RelA/Cbp	0.029	0.16	-10000	0	-0.5	6	6
JUN (dimer)	-0.33	0.3	-10000	0	-0.68	184	184
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.42	-10000	0	-1	101	101
NR3C1	0.22	0.19	0.47	139	-10000	0	139
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	0.49	70	-0.51	5	75
cortisol/GR alpha (dimer)/Src-1	0.32	0.24	0.58	182	-10000	0	182
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	106	106
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.4	124	-0.4	1	125
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.22	0.55	178	-10000	0	178
mol:cortisol	0.21	0.2	0.4	194	-10000	0	194
MMP1	-0.21	0.15	-10000	0	-10000	0	0

×

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	-1.2	88	88
IL23A	-0.22	0.56	-10000	0	-1.2	91	91
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	-1.3	96	96
ITGA3	-0.19	0.51	-10000	0	-1.1	89	89
IL17F	-0.1	0.34	-10000	0	-0.73	77	77
IL12B	-0.004	0.11	-10000	0	-0.59	14	14
STAT1 (dimer)	-0.23	0.58	-10000	0	-1.3	91	91
CD4	-0.19	0.5	-10000	0	-1.1	85	85
IL23	-0.23	0.53	-10000	0	-1.2	89	89
IL23R	-0.003	0.099	-10000	0	-10000	0	0
IL1B	-0.23	0.58	-10000	0	-1.3	91	91
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	-0.78	26	26
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	-1.3	96	96
natural killer cell activation	0.001	0.009	0.036	1	-10000	0	1
JAK2	0.019	0.061	-10000	0	-0.84	2	2
PIK3R1	0.014	0	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
RELA	0.013	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.21	0.5	-10000	0	-1.1	90	90
ALOX12B	-0.21	0.51	-10000	0	-1.1	87	87
CXCL1	-0.22	0.53	-10000	0	-1.2	90	90
T cell proliferation	-0.24	0.61	-10000	0	-1.3	96	96
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.058	0.28	-10000	0	-0.58	61	61
PI3K	-0.3	0.48	-10000	0	-1.2	91	91
IFNG	-0.02	0.055	-10000	0	-0.12	91	91
STAT3 (dimer)	-0.28	0.44	-10000	0	-1.1	88	88
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	-0.56	50	50
macrophage activation	-0.014	0.018	-10000	0	-0.044	97	97
TNF	-0.26	0.62	-10000	0	-1.3	105	105
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	88	88
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	116	116
MPO	-0.2	0.51	-10000	0	-1.1	89	89
positive regulation of humoral immune response	-0.24	0.61	-10000	0	-1.3	96	96
IL23/IL23R/JAK2/TYK2	-0.29	0.74	-10000	0	-1.5	96	96
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	91	91
keratinocyte proliferation	-0.24	0.61	-10000	0	-1.3	96	96
NOS2	-0.2	0.5	-10000	0	-1.1	89	89

×

TCR signaling in naïve CD8+ T cells

Figure S23. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S23. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.61	79	79
FYN	-0.11	0.35	-10000	0	-0.82	81	81
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.66	89	89
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.055	0.22	-10000	0	-0.48	89	89
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.05	-10000	0	-0.18	15	15
MAP3K8	0.002	0.097	-10000	0	-0.82	7	7
mol:Ca2+	-0.031	0.05	-10000	0	-0.12	108	108
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.1	0.32	-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	-0.84	93	93
PRF1	-0.11	0.35	-10000	0	-0.9	71	71
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.037	0.18	-10000	0	-0.38	89	89
LAT	-0.12	0.35	-10000	0	-0.82	85	85
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.092	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	65	65
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.057	0.091	-10000	0	-0.26	62	62
PRKCA	-0.059	0.13	-10000	0	-0.3	96	96
GRAP2	-0.045	0.21	-10000	0	-0.75	38	38
mol:IP3	-0.052	0.23	0.27	87	-0.46	89	176
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	-0.99	86	86
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	-0.72	124	124
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	-0.99	86	86
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	-0.3	70	70
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	-0.72	26	26
PDK1/PKC theta	-0.069	0.27	-10000	0	-0.6	88	88
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	-0.78	90	90
STIM1	0.047	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.091	-10000	0	-0.18	52	52
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	-0.41	90	90
RAP1A/GDP	0.006	0.03	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.024	0.16	-10000	0	-0.62	30	30
cytotoxic T cell degranulation	-0.11	0.33	-10000	0	-0.83	73	73
RAP1A/GTP	-0.003	0.009	-10000	0	-10000	0	0
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	-0.62	89	166
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	-0.62	90	90
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	-0.31	88	88
PRKCE	-0.052	0.12	-10000	0	-0.3	73	73
PRKCQ	-0.092	0.31	-10000	0	-0.69	89	89
LCP2	0.008	0.043	-10000	0	-0.31	9	9
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.041	0.18	-10000	0	-0.4	88	88
IKK complex	0.014	0.068	-10000	0	-0.12	56	56
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

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.42	160	160
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	-0.77	16	16
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.058	0.16	-10000	0	-0.53	16	16
PXN	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.19	-10000	0	-0.72	14	14
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.099	0.17	-10000	0	-0.42	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	-0.8	13	13
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	-0.46	114	114
PI3K	-0.14	0.22	-10000	0	-0.47	115	115
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	-0.77	16	16
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	-0.83	16	16
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

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.087	0.15	-9999	-0.32	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

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.26	0.32	-9999	-0.59	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	-0.55	29	29
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

×

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	142	142
ARAP2	0.01	0.052	-9999	-0.82	2	2
mol:GDP	-0.12	0.14	-9999	-0.31	136	136
mol:PI-3-4-5-P3	0	0	-9999	-0.001	109	109
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	145	145
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	151	151
actin filament binding	0	0	-9999	-0.001	139	139
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	131	131
ARF6/GDP	0	0.069	-9999	-0.33	2	2
ARF6/GDP/GULP/ACAP1	-0.19	0.2	-9999	-0.5	114	114
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.066	0.18	-9999	-0.54	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	118	118
endosomal lumen acidification	0	0	-9999	-0.001	145	145
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	40	40
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	139	139
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	-10000	0	-0.82	1	1
JMJD2C	-0.065	0.069	-10000	0	-0.12	289	289
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	-10000	0	-0.8	7	7
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	218	218
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	213	213
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	132	132
SRF	0.028	0.04	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-0.63	15	15
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	35	35
CCND1	0.001	0.05	-10000	0	-0.31	12	12
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.032	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	-0.58	27	27
Syndecan-1/Syntenin	-0.092	0.16	-9999	-0.56	30	30
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	-0.57	27	27
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.66	54	54
Syndecan-1/CD147	-0.081	0.15	-9999	-0.64	19	19
Syndecan-1/Syntenin/PIP2	-0.099	0.14	-9999	-0.54	30	30
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.097	0.14	-9999	-0.52	30	30
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	-0.63	91	91
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	-10000	0	0
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	-0.51	18	18
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	-0.43	11	11
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	-0.49	4	4
ruffle organization	-0.11	0.22	-10000	0	-0.55	11	11
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.018	0.11	-10000	0	-0.45	24	24
Ephrin B/EPHB2/KALRN	-0.013	0.067	-10000	0	-0.46	10	10
ROCK1	-0.074	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	-0.32	344	344
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	83	83
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	-0.44	34	34
TBX21	-0.12	0.44	-10000	0	-1.1	63	63
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	-0.9	66	66
IL12RB2	-0.014	0.16	-10000	0	-0.72	21	21
GADD45G	-0.075	0.34	-10000	0	-0.86	53	53
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	67	67
HLA-DRB5	-0.041	0.13	-10000	0	-0.35	72	72
FASLG	-0.14	0.48	-10000	0	-1.2	73	73
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.86	70	70
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	54	54
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	-0.56	50	50
NOS2	-0.089	0.34	-10000	0	-0.86	54	54
IL12/IL12R/TYK2/JAK2/SPHK2	-0.025	0.15	-10000	0	-0.4	37	37
IL1R1	-0.088	0.37	-10000	0	-0.97	51	51
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	-0.73	38	38
lysosomal transport	-0.037	0.28	-10000	0	-0.66	48	48
FOS	-0.4	0.65	-10000	0	-1.3	159	159
STAT4 (dimer)	-0.08	0.35	-10000	0	-0.82	63	63
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.87	98	98
GZMA	-0.11	0.41	-10000	0	-1.1	53	53
GZMB	-0.1	0.39	-10000	0	-0.96	62	62
HLX	0.004	0.054	-10000	0	-0.31	14	14
LCK	-0.11	0.42	-10000	0	-1	67	67
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	-0.78	68	68
CCR5	-0.099	0.4	-10000	0	-1.1	51	51
IL1B	-0.043	0.22	-10000	0	-0.76	39	39
STAT6	-0.005	0.11	-10000	0	-0.26	8	8
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	34	-10000	0	34
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	74	74
MAP2K3	-0.072	0.34	-10000	0	-0.77	68	68
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.078	0.35	-10000	0	-0.78	74	74
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	-0.6	7	7
EOMES	-0.15	0.43	-10000	0	-1.5	45	45
STAT1 (dimer)	-0.14	0.37	-10000	0	-0.77	100	100
T cell proliferation	-0.05	0.27	-10000	0	-0.6	62	62
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	-0.73	67	67

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.05	0.21	-10000	0	-0.65	23	23
CRP	-0.056	0.21	-10000	0	-0.64	28	28
cell cycle arrest	-0.071	0.23	-10000	0	-0.71	32	32
TIMP1	-0.15	0.22	-10000	0	-0.56	50	50
IL6ST	-0.11	0.29	-10000	0	-0.82	72	72
Rac1/GDP	-0.078	0.24	-10000	0	-0.58	63	63
AP1	-0.19	0.32	-10000	0	-0.69	127	127
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.092	0.22	-10000	0	-0.64	30	30
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	-0.8	52	52
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	-0.65	72	72
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	-0.59	66	66
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	-0.38	2	2
STAT3	-0.084	0.24	-10000	0	-0.77	32	32
STAT1	-0.01	0.022	-10000	0	-10000	0	0
CEBPD	-0.05	0.21	-10000	0	-0.7	15	15
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	-0.62	51	51
MAPK11	-0.084	0.29	-10000	0	-0.78	55	55
STAT3 (dimer)/FOXO1	-0.001	0.2	0.43	1	-0.57	22	23
GRB2/SOS1/GAB family	-0.11	0.19	-10000	0	-0.64	36	36
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	-0.58	19	19
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	-0.88	28	28
FGG	-0.059	0.21	-10000	0	-0.65	26	26
macrophage differentiation	-0.071	0.23	-10000	0	-0.71	32	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.17	0.28	-10000	0	-0.56	148	148
JUNB	-0.056	0.23	-10000	0	-0.71	30	30
FOS	-0.2	0.36	-10000	0	-0.82	128	128
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.088	0.27	-10000	0	-0.46	139	139
STAT1/PIAS1	-0.072	0.23	-10000	0	-0.54	64	64
GRB2/SOS1/GAB family/SHP2/PI3K	0.039	0.06	-10000	0	-0.73	2	2
STAT3 (dimer)	-0.081	0.24	-10000	0	-0.75	32	32
PRKCD	-0.056	0.22	-10000	0	-0.62	40	40
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	-0.59	62	62
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	-0.6	30	30
IRF1	-0.05	0.21	-10000	0	-0.68	18	18
mol:GDP	-0.089	0.25	-10000	0	-0.56	79	79
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.092	0.26	-10000	0	-0.57	79	79
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.095	0.29	-10000	0	-0.8	54	54
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

×

Hedgehog signaling events mediated by Gli proteins

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
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	-0.28	1	1
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	-0.61	146	146
MIM/GLI1	-0.45	0.39	-9999	-0.76	254	254
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 S35. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.042	0.12	-9999	-0.46	29	29
alphaM/beta2 Integrin/GPIbA	-0.053	0.14	-9999	-0.49	38	38
alphaM/beta2 Integrin/proMMP-9	-0.093	0.2	-9999	-0.55	66	66
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	-0.42	21	21
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	-0.33	52	52
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	-0.33	52	52
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	-1.1	95	95
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	45	45
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	-0.53	7	7
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	-0.44	39	39
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	-0.33	52	52
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	61	61
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	40	40
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

×

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	19	19
ATF2/c-Jun	-0.22	0.42	-9999	-0.97	114	114
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	-0.47	20	20
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	114	114
PPARGC1A	-0.23	0.25	-9999	-0.46	243	243
USF1	-0.025	0.13	-9999	-0.41	40	40
RAB5/GDP/GDI1	-0.036	0.082	-9999	-0.41	4	4
NOS2	-0.045	0.16	-9999	-0.64	9	9
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	20	20
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	-0.44	19	19
RPS6KA4	-0.025	0.13	-9999	-0.47	20	20
PLA2G4A	-0.045	0.19	-9999	-0.59	45	45
GDI1	-0.025	0.13	-9999	-0.47	20	20
TP53	-0.033	0.16	-9999	-0.51	40	40
RPS6KA5	-0.074	0.2	-9999	-0.49	70	70
ESR1	-0.06	0.2	-9999	-0.54	55	55
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.026	0.13	-9999	-0.41	41	41
MEF2A	-0.026	0.13	-9999	-0.48	21	21
EIF4EBP1	-0.045	0.15	-9999	-0.46	40	40
KRT19	-0.1	0.2	-9999	-0.64	36	36
ELK4	-0.025	0.13	-9999	-0.41	40	40
ATF6	-0.025	0.13	-9999	-0.41	40	40
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

×

Osteopontin-mediated events

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	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	-0.84	116	116
ILK	-0.031	0.15	-9999	-0.48	39	39
bone resorption	-0.047	0.15	-9999	-0.53	21	21
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	-0.65	112	112

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	43	43
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	-0.14	2	2
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	0.33	15	-10000	0	15
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.22	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	-1.1	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.029	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.016	0.079	-10000	0	-1.1	1	1
MAPK14	-0.012	0.11	-10000	0	-0.23	42	42
TGM2/GTP	-0.061	0.2	-10000	0	-0.43	74	74
MAPK11	-0.012	0.11	-10000	0	-0.23	70	70
ARHGEF1	-0.01	0.088	-10000	0	-0.18	29	29
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.046	0.18	-10000	0	-0.39	73	73
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.04	0.15	-10000	0	-0.3	77	77
cAMP biosynthetic process	-0.049	0.16	-10000	0	-0.36	73	73
Gq family/GTP/EBP50	-0.045	0.12	-10000	0	-0.35	23	23
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.034	0.069	-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	-0.33	9	9
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	-0.5	12	12
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	72	72
PRKCD	-0.045	0.17	-10000	0	-0.38	72	72
PRKCG	-0.049	0.17	-10000	0	-0.39	72	72
muscle contraction	-0.061	0.21	-10000	0	-0.49	73	73
PRKCZ	-0.034	0.16	-10000	0	-0.35	70	70
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	75	75
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

×

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	-0.57	25	25
ELK1	0.008	0.01	-9999	-10000	0	0
BRAF	-0.039	0.12	-9999	-0.57	23	23
mol:GTP	-0.001	0.003	-9999	-0.006	127	127
MAPK1	-0.029	0.12	-9999	-0.51	19	19
RAF1	-0.039	0.12	-9999	-0.57	23	23
KRAS	0.013	0.002	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.2	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.029	0.1	0.26	5	-0.37	37	42
MAP2K4	-0.019	0.16	-10000	0	-0.4	39	39
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	-0.28	16	16
MAP3K7	0.011	0.005	-10000	0	-10000	0	0
RB1	0.024	0.079	0.28	40	-0.31	1	41
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	-0.44	96	96
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

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.42	35	-10000	0	35
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	-10000	0	0
T-helper 2 cell differentiation	0.067	0.15	0.42	35	-10000	0	35
T cell proliferation during immune response	0.067	0.15	0.42	35	-10000	0	35
MAPKKK cascade	-0.067	0.15	-10000	0	-0.42	35	35
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	-0.6	35	35
IL27/IL27R/JAK2/TYK2	-0.068	0.15	-10000	0	-0.43	34	34
positive regulation of T cell mediated cytotoxicity	-0.067	0.15	-10000	0	-0.42	35	35
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	-10000	0	0
mast cell activation	0.067	0.15	0.42	35	-10000	0	35
IFNG	-0.021	0.049	-10000	0	-0.13	71	71
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	-0.54	32	32
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	-0.57	39	39
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 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
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	0.34	47	-10000	0	47
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	-0.34	47	47
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	-0.68	12	12
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.021	0.08	-10000	0	-0.33	23	23
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	-0.57	121	121
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	-0.62	25	25
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	-0.34	47	47
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	64	64
MMP2	0.016	0.14	-10000	0	-0.48	29	29

×

Regulation of Androgen receptor activity

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
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	-0.56	16	16
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	-0.38	131	131
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	145	145
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	297	297
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

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.016	-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	-0.45	14	14
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	-0.46	14	14
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	-0.45	9	9
Na + (4 Units)	-0.023	0.076	-9999	-0.43	9	9
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

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.5	18	18
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.007	0.058	-9999	-0.49	7	7
LAMA3	-0.025	0.16	-9999	-0.57	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	-0.82	11	11
calcineurin-NFAT signaling pathway	-0.13	0.25	-9999	-0.55	130	130

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.038	0.037	-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	-0.21	1	1
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	-0.21	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.082	-9999	-0.58	4	4
NR1H4	0.001	0.032	-9999	-0.31	5	5
RXRs/LXRs/DNA	-0.098	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

×

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	-0.38	14	14
BLK	-0.25	0.37	-9999	-0.82	148	148
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	-0.34	5	5
positive regulation of innate immune response	-0.06	0.14	-9999	-0.4	13	13
LCK	-0.01	0.11	-9999	-0.42	27	27
p38alpha-beta/MKP7	-0.05	0.13	-9999	-0.46	5	5
p38alpha-beta/MKP5	-0.052	0.13	-9999	-0.5	6	6
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	76	76
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

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.01	0.12	-9999	-0.38	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	-0.28	12	12
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	-0.36	2	2
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	-0.3	5	5
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	-0.46	33	33
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	-0.57	34	34
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

×

Integrins in angiogenesis

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
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	-0.5	23	23
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	-0.61	119	119
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	-0.74	16	16
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.094	0.15	-9999	-0.74	16	16
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.034	0.15	-9999	-0.61	28	28
cell adhesion	-0.029	0.099	-9999	-0.53	16	16
ANGPTL3	0.006	0.026	-9999	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.071	-9999	-0.62	6	6
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.008	0.064	-9999	-0.82	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	-0.41	17	17
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	-0.84	4	4
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

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.044	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	-0.27	40	40
RHOA	0.031	0.046	-9999	-0.26	1	1
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.003	0.074	-9999	-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	40	40
HRAS/GDP	-0.001	0.013	-9999	-0.21	2	2
positive regulation of microtubule depolymerization	0.009	0.087	-9999	-0.36	9	9
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	-0.63	43	43
ADCY9	-0.013	0.19	-9999	-0.61	40	40
GSK3B	0.009	0.081	-9999	-0.3	12	12
arachidonic acid secretion	-0.006	0.18	-9999	-0.57	40	40
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	40	40
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	-0.56	42	42
LPA/LPA3	-0.01	0.044	-9999	-0.21	21	21
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	-0.31	21	21
LPAR1	-0.049	0.23	-9999	-0.83	39	39
IL8	-0.13	0.2	-9999	-0.48	58	58
PTK2	-0.009	0.15	-9999	-0.5	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.013	0.13	-9999	-0.44	40	40
EGFR	0.005	0.082	-9999	-0.82	5	5
PLCG1	-0.017	0.086	-9999	-0.29	14	14
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	-0.36	39	39
HRAS/GTP	-0.008	0.19	-9999	-0.59	40	40
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	-0.58	40	40
mol:LPA	0.003	0.018	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.028	0.13	-9999	-0.53	14	14
MAPKKK cascade	-0.006	0.18	-9999	-0.57	40	40
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	-0.35	2	2
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.009	0.089	-9999	-0.37	9	9
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

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.19	-9999	-0.47	65	65
IKBKB	-0.019	0.073	-9999	-0.29	7	7
AKT1	-0.043	0.1	-9999	-0.27	23	23
IKBKG	-0.018	0.077	-9999	-0.3	8	8
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	-0.65	18	18
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	115	115
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	-0.51	112	112
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	80	80
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	-0.61	53	53
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.035	-9999	-0.13	19	19
VAV2	-0.14	0.19	-9999	-0.85	13	13
ubiquitin-dependent protein catabolic process	0.007	0.028	-9999	-0.11	3	3
BTK	-0.018	0.16	-9999	-1.2	8	8
CD19	-0.15	0.2	-9999	-0.6	36	36
MAP4K1	-0.021	0.13	-9999	-0.82	7	7
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	-0.56	15	15
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	1	1
RasGAP/p62DOK/SHIP	-0.14	0.2	-9999	-0.46	112	112
CD79A	-0.2	0.3	-9999	-0.52	195	195
re-entry into mitotic cell cycle	-0.08	0.13	-9999	-0.28	113	113
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	-0.66	35	35
NFKB1	0.012	0.037	-9999	-0.82	1	1
MAPK8	-0.067	0.17	-9999	-0.57	23	23
actin cytoskeleton organization	-0.091	0.18	-9999	-0.68	13	13
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	-0.54	32	32
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	-0.98	23	23
DAPP1	-0.14	0.26	-9999	-1.2	20	20
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	-0.58	102	102
mol:PI-3-4-5-P3	-0.098	0.12	-9999	-0.38	26	26
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	-0.49	88	88
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.052	-9999	-0.82	2	2
RAC1	-0.097	0.19	-9999	-0.75	13	13
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.55	88	88
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	-0.82	21	21
PDPK1	-0.045	0.1	-9999	-0.27	23	23
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

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.057	0.16	-9999	-0.55	43	43
MAP4K1	-0.021	0.13	-9999	-0.82	7	7
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	-0.75	38	38
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.019	0.11	-9999	-0.52	7	7
LAT	0.005	0.077	-9999	-0.65	6	6
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	-0.37	34	34
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.053	0.15	-9999	-0.52	43	43

×

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

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
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	-10000	0	0
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	-0.69	2	2
INPP5D	-0.003	0.071	-10000	0	-0.31	25	25
CBL/CRK	-0.022	0.11	-10000	0	-10000	0	0
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	-0.48	26	26
DOCK1	-0.025	0.12	-10000	0	-0.55	4	4
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	-0.3	25	25
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	-0.3	25	25
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	-10000	0	0
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	-0.53	3	3
MET/Glomulin	-0.058	0.093	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.036	0.14	-10000	0	-10000	0	0
MET	-0.1	0.16	-10000	0	-0.31	182	182
MAP4K1	-0.027	0.12	-10000	0	-0.54	4	4
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.036	0.14	-10000	0	-10000	0	0
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	-0.32	25	25
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	-0.6	75	75

×

Angiopoietin receptor Tie2-mediated signaling

Figure S55. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S55. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.012	0.22	-10000	0	-0.97	21	21
NCK1/PAK1/Dok-R	-0.028	0.09	-10000	0	-0.43	21	21
NCK1/Dok-R	-0.067	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	0.25	13	-0.33	12	25
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	-1.3	22	22
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	21	21
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.018	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	202	202
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	-1.3	22	22
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	-0.37	19	19
negative regulation of cell cycle	-0.006	0.16	-10000	0	-0.58	21	21
ETS1	0.016	0.044	-10000	0	-0.24	2	2
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	21	21

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-10000	0	-0.82	1	1
Jak2/Leptin Receptor	-0.025	0.096	-10000	0	-0.39	18	18
PTP1B/AKT1	-0.004	0.064	-10000	0	-0.32	3	3
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.013	0.07	-10000	0	-0.32	5	5
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	-0.43	22	22
Insulin Receptor/Insulin	-0.016	0.054	-10000	0	-0.44	4	4
HCK	-0.01	0.084	-10000	0	-0.31	36	36
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.004	0.067	-10000	0	-0.34	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	0.32	5	-10000	0	5
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	-0.34	3	3
Crk/p130 Cas	0	0.061	-10000	0	-0.34	2	2
DOK1	0.005	0.063	-10000	0	-0.28	5	5
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	-0.32	5	5
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	-0.38	62	62
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	-0.82	148	148
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	-0.27	10	10
STAT5A	-0.008	0.071	-10000	0	-0.27	10	10
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.069	-10000	0	-0.34	5	5
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

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.002	0.039	-10000	0	-0.63	2	2
Necdin/E2F1	-0.068	0.12	-10000	0	-0.75	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.035	0.1	-10000	0	-0.48	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.28	-10000	0	-0.57	238	238
NT-4/5 (dimer)/p75(NTR)	-0.074	0.18	-10000	0	-0.66	37	37
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.003	0.12	-10000	0	-0.48	23	23
IKBKG	0.013	0	-10000	0	-10000	0	0
BDNF	-0.014	0.14	-10000	0	-0.61	22	22
MGDIs/NGR/p75(NTR)/LINGO1	-0.048	0.12	-10000	0	-0.53	21	21
FURIN	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.057	0.14	-10000	0	-0.54	32	32
LINGO1	-0.003	0.071	-10000	0	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.025	-10000	0	-10000	0	0
proBDNF (dimer)	-0.014	0.14	-10000	0	-0.61	22	22
NTRK1	-0.002	0.062	-10000	0	-0.31	19	19
RTN4R	0.013	0	-10000	0	-10000	0	0
neuron apoptosis	-0.01	0.13	-10000	0	-0.49	26	26
IRAK1	0.013	0	-10000	0	-10000	0	0
SHC1	-0.02	0.13	-10000	0	-0.56	20	20
ARHGDIA	0.013	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.039	0.11	-10000	0	-0.52	20	20
MAGEH1	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.043	0.12	-10000	0	-0.51	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.49	25	25
proNGF (dimer)	0.006	0.069	-10000	0	-0.56	6	6
MAGED1	0.013	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.022	0.16	-10000	0	-0.66	26	26
ZNF274	0.013	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.036	0.1	-10000	0	-0.48	20	20
NGF	0.006	0.069	-10000	0	-0.56	6	6
cell cycle arrest	0.044	0.16	-10000	0	-0.47	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.085	-10000	0	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.064	0.16	-10000	0	-0.58	39	39
NCSTN	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.045	0.12	-10000	0	-0.56	21	21
PSENEN	0.013	0	-10000	0	-10000	0	0
mol:ceramide	-0.009	0.12	-10000	0	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.07	-10000	0	-0.43	2	2
p75(NTR)/beta APP	-0.049	0.13	-10000	0	-0.63	18	18
BEX1	-0.36	0.41	-10000	0	-0.82	223	223
mol:GDP	-0.03	0.13	-10000	0	-0.57	20	20
NGF (dimer)	-0.094	0.13	-10000	0	-0.5	31	31
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.042	0.11	-10000	0	-0.52	18	18
PIK3R1	0.013	0	-10000	0	-10000	0	0
RAC1/GTP	-0.038	0.1	-10000	0	-0.5	20	20
MYD88	0.013	0	-10000	0	-10000	0	0
CHUK	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.045	0.12	-10000	0	-0.56	21	21
RHOB	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.062	0.093	-10000	0	-10000	0	0
NT3 (dimer)	-0.047	0.2	-10000	0	-0.6	49	49
TP53	-0.005	0.13	-10000	0	-0.45	32	32
PRDM4	-0.009	0.12	-10000	0	-0.51	20	20
BDNF (dimer)	-0.13	0.16	-10000	0	-0.53	42	42
PIK3CA	0.008	0.064	-10000	0	-0.82	3	3
SORT1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.034	0.1	-10000	0	-0.48	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.11	-10000	0	-0.52	22	22
RHOC	0.013	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
MAPK10	0.024	0.12	-10000	0	-0.44	20	20
DIABLO	0.013	0	-10000	0	-10000	0	0
SMPD2	-0.009	0.12	-10000	0	-0.51	20	20
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.044	0.12	-10000	0	-0.56	20	20
PSEN1	0.013	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-10000	0	-0.63	1	1
NT3 (dimer)/p75(NTR)	-0.092	0.2	-10000	0	-0.66	45	45
MAPK8	0.017	0.13	-10000	0	-0.45	20	20
MAPK9	0.024	0.12	-10000	0	-0.43	19	19
APAF1	0.012	0.037	-10000	0	-0.82	1	1
NTF3	-0.047	0.2	-10000	0	-0.6	49	49
NTF4	-0.022	0.16	-10000	0	-0.66	26	26
NDN	0.005	0.082	-10000	0	-0.82	5	5
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.032	0.094	-10000	0	-0.44	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.053	-10000	0	-0.65	3	3
RhoA-B-C/GTP	-0.045	0.12	-10000	0	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.047	0.12	-10000	0	-0.48	32	32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.052	0.13	-10000	0	-0.51	32	32
PRKACB	0.012	0.037	-10000	0	-0.82	1	1
proBDNF (dimer)/p75 ECD	-0.022	0.11	-10000	0	-0.63	15	15
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.64	38	38
BIRC2	0.013	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.067	0.17	0.24	193	-0.47	20	213
BAD	0.029	0.12	-10000	0	-0.43	20	20
RIPK2	0.013	0	-10000	0	-10000	0	0
NGFR	-0.06	0.18	-10000	0	-0.42	84	84
CYCS	0	0.11	-10000	0	-0.48	20	20
ADAM17	0.01	0.052	-10000	0	-0.82	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.041	0.11	-10000	0	-0.52	22	22
BCL2L11	0.029	0.12	-10000	0	-0.43	20	20
BDNF (dimer)/p75(NTR)	-0.069	0.16	-10000	0	-0.63	32	32
PI3K	-0.041	0.12	-10000	0	-0.52	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.039	0.11	-10000	0	-0.52	20	20
NDNL2	0.013	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.054	0.14	-10000	0	-0.65	20	20
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.039	0.11	-10000	0	-0.52	20	20
TRAF6	0.01	0.052	-10000	0	-0.82	2	2
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
PLG	-0.004	0.04	-10000	0	-0.31	8	8
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.016	0.14	-10000	0	-0.49	32	32
SQSTM1	0.013	0	-10000	0	-10000	0	0
NGFRAP1	0.013	0	-10000	0	-10000	0	0
CASP3	0.031	0.11	-10000	0	-0.4	20	20
E2F1	-0.087	0.15	-10000	0	-0.31	154	154
CASP9	0.013	0	-10000	0	-10000	0	0
IKK complex	-0.013	0.058	-10000	0	-0.53	3	3
NGF (dimer)/TRKA	-0.013	0.063	-10000	0	-0.63	3	3
MMP7	-0.18	0.22	-10000	0	-0.37	246	246
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.037	0.11	-10000	0	-0.49	22	22
MMP3	-0.04	0.11	-10000	0	-0.31	71	71
APAF-1/Caspase 9	-0.04	0.11	-10000	0	-0.6	7	7

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.037	-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	-0.28	32	32
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

×

Effects of Botulinum toxin

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
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	-0.24	223	223
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

×

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	-1	132	132
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	-0.5	49	49
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	-1.1	120	120
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	-0.42	6	6
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	0.32	37	-10000	0	37
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	-0.68	2	2
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	-0.36	1	1
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	-1.1	118	118
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	-0.38	8	8
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.011	0.02	-9999	-10000	0	0
AURKB	-0.061	0.14	-9999	-0.31	114	114
AURKC	-0.001	0.067	-9999	-0.31	22	22

×

Visual signal transduction: Cones

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
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	-0.21	2	2
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

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.39	87	87
NT-4/5 (dimer)/TRKB	-0.067	0.16	-10000	0	-0.57	42	42
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	-0.27	3	3
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	18	18
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	-0.4	4	4
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	-0.48	25	25
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	-0.67	1	1
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	197	197
FRS2 family/SHP2/CRK family	-0.001	0.02	-10000	0	-0.46	1	1

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-10000	0	0
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	-0.44	46	46
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	-0.57	2	2
axon guidance	-0.001	0.086	-10000	0	-0.43	3	3
NEDD4	0.021	0.056	-10000	0	-0.8	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.042	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	-0.52	11	11
STAT1 (dimer)	-0.009	0.091	-10000	0	-0.45	1	1
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	-0.43	3	3
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	56	56
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	-0.51	1	1
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	-0.44	3	3
ERBB4	-0.012	0.1	-10000	0	-0.52	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.011	0.02	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.026	0.057	-10000	0	-0.5	2	2
glial cell differentiation	0.033	0.063	0.42	1	-10000	0	1
WWOX	0.012	0.037	-10000	0	-0.82	1	1
cell proliferation	-0.024	0.17	-10000	0	-0.46	55	55

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.027	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	-10000	0	0
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	-0.43	125	125
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	-0.55	40	40
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

×

Signaling events mediated by PRL

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
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	-0.64	11	11
AGT	-0.022	0.14	-9999	-0.46	37	37
CCNA2	-0.063	0.2	-9999	-0.58	5	5
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	-0.25	17	17
RHOA	-0.017	0.093	-9999	-10000	0	0
cell motility	-0.016	0.099	-9999	-0.26	17	17
PRL-1/alpha Tubulin	-0.062	0.2	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.026	0.095	-9999	-0.67	7	7
ROCK1	-0.016	0.1	-9999	-0.27	17	17
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.072	0.21	-9999	-0.48	108	108
ATF5	0	0.064	-9999	-0.31	20	20

×

FOXM1 transcription factor network

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
NFATC3	0.053	0.35	-9999	-0.92	13	13
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	-0.92	13	13
MAP2K1	0.032	0.037	-9999	-10000	0	0
BRCA2	0.048	0.36	-9999	-0.98	16	16
FOXM1	0.043	0.39	-9999	-1	19	19
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	-0.85	14	14
CDC2	0.047	0.36	-9999	-0.9	19	19
TGFA	0.024	0.34	-9999	-0.85	16	16
SKP2	0.046	0.36	-9999	-0.97	17	17
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.053	0.35	-9999	-0.92	13	13
RB1	-0.052	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.038	0.36	-9999	-1	18	18
AURKB	-0.005	0.13	-9999	-10000	0	0
CENPF	0.047	0.36	-9999	-0.94	14	14
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	-0.32	168	168
LAMA4	0.053	0.35	-9999	-0.91	14	14
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	-0.91	14	14
response to radiation	0.016	0.034	-9999	-10000	0	0
CENPB	0.053	0.35	-9999	-0.92	13	13
CENPA	0.039	0.37	-9999	-0.98	18	18
NEK2	0.043	0.36	-9999	-0.93	17	17
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	-0.95	14	14
CCNB1	0.049	0.36	-9999	-0.94	15	15
ETV5	0.053	0.35	-9999	-0.92	13	13
ESR1	0.006	0.43	-9999	-1.1	35	35
CCND1	0.043	0.34	-9999	-0.87	14	14
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.051	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.12	0.23	-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

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.001	0.08	-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	34	34
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	-0.38	8	8
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	-0.39	12	12
Aurora B/Septin1	-0.026	0.1	-9999	-0.43	10	10
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	-0.32	174	174
hSgo1/Aurora B/Survivin	-0.024	0.12	-9999	-0.36	37	37
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.03	0.072	-9999	-0.32	17	17
SGOL1	0.001	0.062	-9999	-0.31	19	19
CENPA	-0.008	0.07	-9999	-0.23	16	16
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	-0.35	19	19
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	-0.25	29	29
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

×

Fc-epsilon receptor I signaling in mast cells

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
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	130	130
mol:PIP3	-0.017	0.15	-9999	-0.51	15	15
IKBKB	0.003	0.093	-9999	-0.28	14	14
AKT1	-0.016	0.14	-9999	-0.58	6	6
IKBKG	0.003	0.093	-9999	-0.28	13	13
MS4A2	-0.065	0.14	-9999	-0.33	3	3
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	-0.48	6	6
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	-0.59	5	5
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	-0.42	2	2
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	-0.44	7	7
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	-0.56	8	8
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	-0.55	41	41
Antigen/IgE/Fc epsilon R1	-0.088	0.15	-9999	-0.51	41	41
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	-0.38	4	4
CHUK	0.003	0.093	-9999	-0.28	14	14
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	-0.36	3	3
negative regulation of mast cell degranulation	-0.019	0.1	-9999	-0.39	12	12
BTK	-0.022	0.12	-9999	-0.61	11	11
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.048	0.19	-9999	-0.53	45	45
GAB2/PI3K/SHP2	-0.063	0.13	-9999	-0.66	6	6
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.018	0.093	-9999	-0.32	9	9
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	-0.48	40	40
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.82	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	-0.62	7	7
FER	-0.012	0.096	-9999	-0.51	4	4
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	-10000	0	0
SPHK1	-0.013	0.091	-9999	-0.45	2	2
PTK2	-0.005	0.085	-9999	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.066	0.13	-9999	-0.44	41	41
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	-0.37	24	24
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	-0.4	12	12
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

×

Insulin-mediated glucose transport

Figure S70. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S70. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.003	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	-10000	0	16
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	-0.26	59	59
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	-0.34	315	315
LNPEP	-0.013	0.15	-10000	0	-0.82	16	16
YWHAE	0.013	0	-10000	0	-10000	0	0

×

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	0.2	1	-10000	0	1
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.1	0.16	-10000	0	-0.31	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	0.19	1	-0.17	1	2
PI3K	-0.038	0.095	0.23	1	-0.23	48	49
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

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.22	1	1
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	-1.1	1	1
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	-0.62	2	2
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

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.82	11	11
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

×

IL2 signaling events mediated by STAT5

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
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	-0.57	19	19
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.044	0.25	-9999	-0.98	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 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
CBL/APS/CAP	-0.057	0.15	-9999	-0.44	65	65
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	-0.56	2	2
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	-10000	0	0
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	-0.39	58	58
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	-1	2	2
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	-10000	0	0
AKT2	-0.015	0.16	-9999	-0.88	2	2
PRKCZ	-0.015	0.034	-9999	-10000	0	0
SH2B2	0.011	0.04	-9999	-0.56	2	2
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

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-10000	0	0
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

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	68	68
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.021	0.16	-9999	-0.4	68	68
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	-0.4	68	68
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	-0.4	68	68
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	-0.46	6	6
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	-0.74	1	1
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	-0.62	4	4
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	-0.74	2	2
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	-0.46	6	6
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	-0.59	4	4
RAP1/GDP	-0.042	0.1	-9999	-0.6	1	1
CBL	-0.018	0.16	-9999	-0.4	68	68
MAP3K1	-0.017	0.16	-9999	-0.4	68	68
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

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.021	0.029	0.62	1	-10000	0	1
CDKN1A	-0.006	0.035	-10000	0	-10000	0	0
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
FOXO3	0	0.007	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.024	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	0.006	0.033	-10000	0	-0.31	5	5
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.019	-10000	0	-10000	0	0
PPARGC1A	-0.36	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

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.9	1	1
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.017	0.15	-9999	-0.84	1	1
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	-0.48	19	19
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	-1.2	1	1
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	-0.31	42	42
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	-1.2	1	1
mol:L-citrulline	0.017	0.15	-9999	-0.84	1	1
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	-1.2	1	1
PDPK1	0	0.16	-9999	-1.2	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.005	0.082	-9999	-0.89	3	3
mol:NADP	0.017	0.15	-9999	-0.84	1	1
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

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

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

×

a4b1 and a4b7 Integrin signaling

Figure 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	-0.88	2	2
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	-0.6	18	18
AKT1	0.009	0.18	-10000	0	-0.61	22	22
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	-0.46	35	35
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	-0.012	5	5
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	-0.55	25	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.03	0.038	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.008	0.16	-10000	0	-0.53	25	25
Rac1/GDP	0.024	0.042	-10000	0	-0.5	3	3
T cell proliferation	0.016	0.15	-10000	0	-0.59	14	14
SHC1	0.013	0.004	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.011	-10000	0	-0.052	17	17
PRKCZ	0.015	0.15	-10000	0	-0.64	13	13
NF kappa B1 p50/RelA	-0.059	0.14	-10000	0	-0.52	21	21
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	-0.59	14	14
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

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.003	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	0.2	1	-10000	0	1
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	-0.1	15	15
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 S88. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.012	0.037	-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	-0.78	25	25
MAP2K7	0.024	0.081	-9999	-10000	0	0
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	-0.4	2	2
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 S89. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.024	0.096	-9999	-0.49	2	2
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	-0.39	55	55
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	-0.48	1	1
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	-0.57	1	1
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	-10000	0	0
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 S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.017	0.093	-10000	0	-0.46	13	13
ACTA1	0.008	0.12	0.24	20	-0.58	13	33
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	-0.31	2	2
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	-0.59	12	12
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	-0.4	4	4
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	0.24	22	-0.61	13	35
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	0.25	22	-0.5	11	33
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	-0.56	18	18
positive regulation of apoptosis	0.023	0.078	-10000	0	-0.31	4	4
PRF1	-0.003	0.11	-10000	0	-0.69	12	12

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.65	3	4
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	-10000	0	-0.35	3	3
MAP3K5	0.011	0.021	-10000	0	-0.45	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.021	-10000	0	-0.45	1	1
mol:LY294002	0	0.001	0.001	1	-0.002	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	-0.51	2	2
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	-0.79	3	4
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

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.31	2	2
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.018	0.083	-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	-0.34	315	315
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	-0.5	24	24
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	-0.4	11	11
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

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.033	0.3	1	-0.53	1	2
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	-10000	0	-10000	0	0
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	1	1
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	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.051	0.16	-10000	0	-0.6	14	14
BLK	-0.25	0.37	-10000	0	-0.82	148	148
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	-10000	0	-0.49	2	2
CYTH2	0	0.013	-10000	0	-10000	0	0
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	-10000	0	-10000	0	0
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	-0.65	6	6
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	-10000	0	-0.43	8	8

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-10000	0	0
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	-0.41	25	25
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

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.41	19	19
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	-0.21	1	1
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	-0.35	55	55
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	-0.36	19	19
RXRB	0.009	0.09	-10000	0	-0.44	19	19
VDR/Vit D3/DNA	0	0.01	-10000	0	-0.21	1	1
RBP1	-0.004	0.11	-10000	0	-0.66	13	13
CRBP1/9-cic-RA	-0.013	0.086	-10000	0	-0.5	13	13
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	-0.39	19	19
NRIP1	-0.023	0.14	-10000	0	-0.61	20	20
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 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
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	17	17
VEGFR1 homodimer/VEGFA homodimer	0.024	0.066	-9999	-0.79	3	3
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.068	0.17	-9999	-0.35	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

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.039	0.016	-10000	0	-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	-0.37	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.039	0.016	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.015	-10000	0	-10000	0	0
mTORC2	-0.001	0.023	-10000	0	-0.51	1	1
AKT2	0.016	0.029	-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	-0.34	315	315
G1/S transition of mitotic cell cycle	0.046	0.015	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.001	0.053	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
KPNA1	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

Figure 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	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	-0.32	4	4
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.064	-9999	-0.82	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 S100. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S100. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	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	-0.5	18	18
GNAO1	-0.016	0.15	-9999	-0.7	21	21
PDGFB-D/PDGFRB/PLCgamma1	0.025	0.13	-9999	-0.54	10	10
PLCG1	0.023	0.13	-9999	-0.6	9	9
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	-0.48	18	18
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	41	41
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	-0.48	18	18
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 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	-10000	0	-10000	0	0
AES	0.005	0.02	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	-0.026	0.17	-10000	0	-0.66	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	26	-10000	0	26
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	0.21	1	-10000	0	1
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	-0.47	4	4
DKK1/LRP6/Kremen 2	-0.038	0.08	-10000	0	-0.4	8	8
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	-10000	0	-10000	0	0

×

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

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.61	7	7
p130Cas/Crk/Dock1	0.04	0.079	-9999	-0.81	1	1
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

×

FoxO family signaling

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
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	-0.34	315	315
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.017	0.065	-9999	-0.32	5	5
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

×

Canonical NF-kappaB 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
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

×

S1P5 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.011	0.054	0.29	17	-10000	0	17
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.003	0.031	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.016	0.15	-10000	0	-0.7	21	21
RhoA/GTP	-0.012	0.055	-10000	0	-0.3	17	17
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

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.021	0.12	-9999	-0.66	16	16
AKT1	0.084	0.089	-9999	-0.68	5	5
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	-0.61	39	39
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	-0.82	6	6
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	-0.73	6	6
MAPK1	0.045	0.1	-9999	-0.64	8	8
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	-0.78	7	7
SRC	0.013	0.015	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.047	0.11	-9999	-0.67	8	8
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	-0.7	4	4
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	-0.68	7	7
mol:NO	0.076	0.066	-9999	-0.56	4	4
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.081	-9999	-0.74	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.049	0.12	-9999	-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	-0.62	9	9
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	-0.31	42	42
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 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
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	-0.15	11	11
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.045	0.002	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0.002	-9999	-10000	0	0
WASF2	0.002	0.008	-9999	-10000	0	0
Rap1/GTP	0	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.078	-9999	-0.46	14	14
CCND1	0.015	0.039	-9999	-0.18	11	11
VAV2	0.056	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.045	0.001	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.016	0.074	-9999	-0.43	14	14
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.044	0.009	-9999	-10000	0	0
PIK3CA	0.008	0.064	-9999	-0.82	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

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.33	17	17
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	-0.62	15	15
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

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.05	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	-10000	0	0
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	-10000	0	0
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

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.06	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	-0.47	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
GATA1	0.008	0.016	-9999	-0.31	1	1
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.022	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.008	0.064	-9999	-0.82	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	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.044	0.027	-9999	-10000	0	0
SIN3 complex	-0.001	0.022	-9999	-0.49	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.037	-9999	-0.82	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	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.032	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.027	0	-9999	-10000	0	0
NFKB1	0.012	0.037	-9999	-0.82	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	-10000	0	0
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

×

Atypical NF-kappaB pathway

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
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	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.047	0.038	-9999	-0.4	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
PI3K	-0.004	0.048	-9999	-0.63	3	3
NF kappa B1 p50/RelA	0.031	0.038	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	0.045	0.036	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.01	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

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.001	0.025	-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	-0.96	3	3
EPAS1	0.1	0.1	-10000	0	-0.63	3	3
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	-0.57	21	21
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 S115. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.032	0	-9999	-10000	0	0
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.031	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

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.007	-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	-0.65	3	3
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	-0.76	3	3

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.56	2	2
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	-0.44	14	14
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	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.001	0.029	-9999	-0.64	1	1
PTPRJ	0.013	0	-9999	-10000	0	0

×

S1P4 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
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	-0.3	17	17
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.011	0.052	-9999	-0.31	1	1
S1PR5	0.007	0.053	-9999	-0.38	8	8
S1PR4	0.009	0.038	-9999	-10000	0	0
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 S119. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.03	-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 S120. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	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 S121. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.022	-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	-10000	0	0
nuclear import	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
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 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
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

×

PLK1 signaling events

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
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	-10000	0	0
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	-10000	0	0
microtubule cytoskeleton organization	0.015	0.007	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-9999	-0.011	3	3
PPP1R12A	0.013	0	-9999	-10000	0	0
interphase	0	0.001	-9999	-0.011	3	3
PLK1/PRC1-2	0.008	0.058	-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	-0.18	1	1
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	-10000	0	0
INCENP	0.009	0.053	-9999	-0.82	2	2

×

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	-10000	0	0
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

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.081	0.11	-9999	-9999
TP53	-0.027	0.033	-9999	-9999
Senescence	-0.027	0.033	-9999	-9999
Apoptosis	-0.027	0.033	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.052	0.062	-9999	-9999
MDM4	0.013	0	-9999	-9999

×

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	-0.25	2	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.002	0.026	-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	-10000	0	0
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