PARADIGM pathway analysis of mRNASeq expression data - Breast Invasive Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by Stem cell factor receptor (c-Kit)	281
Class IB PI3K non-lipid kinase events	280
EGFR-dependent Endothelin signaling events	234
Reelin signaling pathway	228
HIF-1-alpha transcription factor network	207
Signaling mediated by p38-alpha and p38-beta	198
FOXA2 and FOXA3 transcription factor networks	165
p75(NTR)-mediated signaling	162
Glucocorticoid receptor regulatory network	155
Angiopoietin receptor Tie2-mediated signaling	148

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
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2710	281	21957	78	-0.62	0.19	1000	-1000	-0.066	-1000
Class IB PI3K non-lipid kinase events	0.2700	280	840	3	-0.22	-1000	1000	-1000	-0.031	-1000
EGFR-dependent Endothelin signaling events	0.2257	234	4921	21	-0.34	0	1000	-1000	-0.055	-1000
Reelin signaling pathway	0.2199	228	12810	56	-0.48	0	1000	-1000	-0.095	-1000
HIF-1-alpha transcription factor network	0.1996	207	15775	76	-0.76	0.019	1000	-1000	-0.08	-1000
Signaling mediated by p38-alpha and p38-beta	0.1909	198	8715	44	-0.4	0	1000	-1000	-0.046	-1000
FOXA2 and FOXA3 transcription factor networks	0.1591	165	7599	46	-1.2	0.024	1000	-1000	-0.031	-1000
p75(NTR)-mediated signaling	0.1562	162	20344	125	-0.39	0	1000	-1000	-0.098	-1000
Glucocorticoid receptor regulatory network	0.1495	155	17682	114	-0.94	0.35	1000	-1000	-0.064	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1427	148	13069	88	-0.37	0.038	1000	-1000	-0.091	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1369	142	7703	54	-0.48	0.022	1000	-1000	-0.092	-1000
FOXM1 transcription factor network	0.1360	141	7240	51	-0.44	0.014	1000	-1000	-0.13	-1000
Arf6 signaling events	0.1321	137	8508	62	-0.34	0.017	1000	-1000	-0.061	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1321	137	9346	68	-0.52	0.17	1000	-1000	-0.12	-1000
Aurora B signaling	0.1311	136	9176	67	-0.32	0.008	1000	-1000	-0.058	-1000
Endothelins	0.1302	135	12966	96	-0.38	0.037	1000	-1000	-0.06	-1000
Wnt signaling	0.1273	132	927	7	-0.17	-0.007	1000	-1000	-0.047	-1000
IL4-mediated signaling events	0.1205	125	11424	91	-1	0.52	1000	-1000	-0.14	-1000
ErbB2/ErbB3 signaling events	0.1176	122	7970	65	-0.4	0.018	1000	-1000	-0.058	-1000
Ephrin B reverse signaling	0.1148	119	5736	48	-0.32	0.18	1000	-1000	-0.064	-1000
EPHB forward signaling	0.1148	119	10129	85	-0.32	0.17	1000	-1000	-0.084	-1000
Syndecan-1-mediated signaling events	0.1032	107	3655	34	-0.22	0	1000	-1000	-0.058	-1000
IGF1 pathway	0.1022	106	6058	57	-0.18	0.081	1000	-1000	-0.091	-1000
Signaling events regulated by Ret tyrosine kinase	0.1013	105	8625	82	-0.17	0	1000	-1000	-0.077	-1000
ErbB4 signaling events	0.1003	104	7212	69	-0.42	0.057	1000	-1000	-0.076	-1000
BMP receptor signaling	0.0964	100	8100	81	-0.55	0.026	1000	-1000	-0.076	-1000
Calcium signaling in the CD4+ TCR pathway	0.0945	98	3052	31	-0.32	0.012	1000	-1000	-0.1	-1000
Noncanonical Wnt signaling pathway	0.0935	97	2531	26	-0.17	0	1000	-1000	-0.069	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0935	97	8299	85	-0.24	0.011	1000	-1000	-0.069	-1000
Nongenotropic Androgen signaling	0.0916	95	4991	52	-0.23	0.1	1000	-1000	-0.053	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0916	95	11467	120	-0.6	0.24	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0897	93	5626	60	-0.46	0.017	1000	-1000	-0.13	-1000
Glypican 1 network	0.0887	92	4451	48	-0.32	0.03	1000	-1000	-0.042	-1000
Plasma membrane estrogen receptor signaling	0.0887	92	7953	86	-0.19	0.094	1000	-1000	-0.076	-1000
Aurora C signaling	0.0839	87	614	7	-0.17	0	1000	-1000	-0.038	-1000
Integrins in angiogenesis	0.0810	84	7098	84	-0.33	0	1000	-1000	-0.088	-1000
Signaling events mediated by PTP1B	0.0791	82	6280	76	-0.65	0.07	1000	-1000	-0.073	-1000
amb2 Integrin signaling	0.0752	78	6421	82	-0.49	0	1000	-1000	-0.079	-1000
IL6-mediated signaling events	0.0752	78	5916	75	-0.28	0.051	1000	-1000	-0.081	-1000
Visual signal transduction: Rods	0.0752	78	4104	52	-0.48	0	1000	-1000	-0.08	-1000
Ephrin A reverse signaling	0.0723	75	526	7	-0.081	0	1000	-1000	-0.025	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0675	70	3666	52	-0.19	0.03	1000	-1000	-0.064	-1000
Syndecan-3-mediated signaling events	0.0665	69	2436	35	-0.36	0	1000	-1000	-0.069	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0656	68	2343	34	-0.095	0	1000	-1000	-0.052	-1000
LPA receptor mediated events	0.0617	64	6561	102	-0.29	0.029	1000	-1000	-0.082	-1000
Signaling events mediated by the Hedgehog family	0.0608	63	3322	52	-0.22	0.03	1000	-1000	-0.081	-1000
PDGFR-alpha signaling pathway	0.0598	62	2758	44	-0.36	0.019	1000	-1000	-0.059	-1000
PLK1 signaling events	0.0588	61	5189	85	-0.22	0.029	1000	-1000	-0.051	-1000
Visual signal transduction: Cones	0.0569	59	2253	38	-0.18	0.008	1000	-1000	-0.059	-1000
Fc-epsilon receptor I signaling in mast cells	0.0569	59	5762	97	-0.24	0.028	1000	-1000	-0.079	-1000
Nectin adhesion pathway	0.0511	53	3393	63	-0.086	0.002	1000	-1000	-0.065	-1000
E-cadherin signaling in keratinocytes	0.0511	53	2285	43	-0.29	0.04	1000	-1000	-0.071	-1000
Presenilin action in Notch and Wnt signaling	0.0501	52	3226	61	-0.42	0.014	1000	-1000	-0.069	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0492	51	1713	33	-0.55	0	1000	-1000	-0.062	-1000
Rapid glucocorticoid signaling	0.0492	51	1025	20	-0.19	0.027	1000	-1000	-0.037	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0482	50	3758	74	-0.29	0.07	1000	-1000	-0.084	-1000
Signaling events mediated by HDAC Class III	0.0473	49	1983	40	-0.57	0.019	1000	-1000	-0.047	-1000
FAS signaling pathway (CD95)	0.0473	49	2339	47	-0.47	0.013	1000	-1000	-0.044	-1000
LPA4-mediated signaling events	0.0444	46	552	12	-0.16	0.02	1000	-1000	-0.02	-1000
TCGA08_rtk_signaling	0.0444	46	1204	26	-0.29	0.027	1000	-1000	-0.03	-1000
Signaling events mediated by PRL	0.0444	46	1583	34	-0.18	0.02	1000	-1000	-0.063	-1000
S1P1 pathway	0.0434	45	1634	36	-0.33	0.008	1000	-1000	-0.072	-1000
IL27-mediated signaling events	0.0424	44	2259	51	-0.29	0.033	1000	-1000	-0.074	-1000
Syndecan-4-mediated signaling events	0.0424	44	2967	67	-0.32	0.005	1000	-1000	-0.076	-1000
Canonical Wnt signaling pathway	0.0415	43	2220	51	-0.42	0.14	1000	-1000	-0.057	-1000
TCR signaling in naïve CD8+ T cells	0.0386	40	3806	93	-0.16	0.079	1000	-1000	-0.07	-1000
Regulation of Androgen receptor activity	0.0366	38	2681	70	-0.26	0.022	1000	-1000	-0.069	-1000
Coregulation of Androgen receptor activity	0.0357	37	2882	76	-0.2	0.035	1000	-1000	-0.047	-1000
IL12-mediated signaling events	0.0357	37	3288	87	-0.35	0.048	1000	-1000	-0.098	-1000
Insulin Pathway	0.0357	37	2794	74	-0.2	0.033	1000	-1000	-0.084	-1000
Ras signaling in the CD4+ TCR pathway	0.0357	37	637	17	-0.12	-0.001	1000	-1000	-0.059	-1000
Osteopontin-mediated events	0.0347	36	1375	38	-0.24	0.022	1000	-1000	-0.086	-1000
Effects of Botulinum toxin	0.0347	36	947	26	-0.098	0.001	1000	-1000	-0.052	-1000
Regulation of nuclear SMAD2/3 signaling	0.0338	35	4787	136	-0.32	0.053	1000	-1000	-0.065	-1000
Regulation of Telomerase	0.0328	34	3501	102	-0.34	0.022	1000	-1000	-0.09	-1000
Thromboxane A2 receptor signaling	0.0309	32	3425	105	-0.29	0.066	1000	-1000	-0.059	-1000
Regulation of p38-alpha and p38-beta	0.0309	32	1737	54	-0.36	0.029	1000	-1000	-0.069	-1000
TCGA08_retinoblastoma	0.0309	32	262	8	-0.052	0.01	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	0.0299	31	2173	69	-0.2	0.034	1000	-1000	-0.054	-1000
IL2 signaling events mediated by STAT5	0.0299	31	703	22	-0.12	0.063	1000	-1000	-0.042	-1000
BCR signaling pathway	0.0280	29	2898	99	-0.13	0.043	1000	-1000	-0.082	-1000
Aurora A signaling	0.0260	27	1651	60	-0.21	0.006	1000	-1000	-0.06	-1000
Arf6 trafficking events	0.0251	26	1907	71	-0.44	0.032	1000	-1000	-0.068	-1000
Hedgehog signaling events mediated by Gli proteins	0.0183	19	1290	65	-0.068	0.04	1000	-1000	-0.07	-1000
TRAIL signaling pathway	0.0183	19	923	48	-0.079	0.044	1000	-1000	-0.057	-1000
Glypican 2 network	0.0183	19	78	4	-0.035	-0.03	1000	-1000	-0.038	-1000
E-cadherin signaling events	0.0183	19	99	5	-0.025	0	1000	-1000	-0.046	-1000
Class I PI3K signaling events mediated by Akt	0.0174	18	1249	68	-0.25	0.054	1000	-1000	-0.062	-1000
Ceramide signaling pathway	0.0174	18	1405	76	-0.18	0.048	1000	-1000	-0.074	-1000
Retinoic acid receptors-mediated signaling	0.0174	18	1093	58	-0.1	0.037	1000	-1000	-0.059	-1000
BARD1 signaling events	0.0164	17	981	57	-0.11	0.024	1000	-1000	-0.064	-1000
Caspase cascade in apoptosis	0.0154	16	1211	74	-0.049	0.045	1000	-1000	-0.062	-1000
Cellular roles of Anthrax toxin	0.0154	16	628	39	-0.14	0.02	1000	-1000	-0.031	-1000
Signaling mediated by p38-gamma and p38-delta	0.0145	15	233	15	-0.018	0.022	1000	-1000	-0.052	-1000
IL2 signaling events mediated by PI3K	0.0145	15	877	58	-0.042	0.06	1000	-1000	-0.074	-1000
PLK2 and PLK4 events	0.0135	14	44	3	-0.012	0.013	1000	-1000	-0.029	-1000
JNK signaling in the CD4+ TCR pathway	0.0135	14	245	17	-0.019	0.043	1000	-1000	-0.061	-1000
E-cadherin signaling in the nascent adherens junction	0.0135	14	1065	76	-0.025	0.048	1000	-1000	-0.071	-1000
IL1-mediated signaling events	0.0125	13	810	62	-0.037	0.032	1000	-1000	-0.084	-1000
S1P5 pathway	0.0116	12	213	17	-0.039	0.022	1000	-1000	-0.055	-1000
S1P3 pathway	0.0116	12	510	42	-0.028	0.022	1000	-1000	-0.057	-1000
p38 MAPK signaling pathway	0.0106	11	491	44	-0.07	0.026	1000	-1000	-0.056	-1000
mTOR signaling pathway	0.0096	10	547	53	-0.02	0.026	1000	-1000	-0.054	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0087	9	262	28	-0.039	0.017	1000	-1000	-0.048	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0087	9	347	37	-0.048	0.033	1000	-1000	-0.071	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0087	9	788	83	-0.039	0.051	1000	-1000	-0.071	-1000
S1P4 pathway	0.0087	9	241	25	-0.039	0	1000	-1000	-0.051	-1000
Signaling events mediated by HDAC Class II	0.0077	8	660	75	-0.16	0	1000	-1000	-0.055	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0077	8	1023	125	-0.17	0.083	1000	-1000	-0.096	-1000
HIF-2-alpha transcription factor network	0.0068	7	313	43	-0.18	0.18	1000	-1000	-0.072	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0068	7	341	45	-0.026	0.073	1000	-1000	-0.089	-1000
VEGFR1 specific signals	0.0068	7	438	56	-0.17	0.065	1000	-1000	-0.07	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0058	6	143	23	-0.03	0.041	1000	-1000	-0.061	-1000
EPO signaling pathway	0.0058	6	380	55	-0.036	0.057	1000	-1000	-0.08	-1000
Class I PI3K signaling events	0.0058	6	454	73	-0.041	0.059	1000	-1000	-0.07	-1000
PDGFR-beta signaling pathway	0.0058	6	657	97	-0.024	0.052	1000	-1000	-0.08	-1000
FoxO family signaling	0.0048	5	343	64	-0.04	0.091	1000	-1000	-0.071	-1000
Atypical NF-kappaB pathway	0.0048	5	164	31	-0.02	0.03	1000	-1000	-0.071	-1000
Circadian rhythm pathway	0.0039	4	100	22	-0.015	0.041	1000	-1000	-0.064	-1000
Signaling events mediated by HDAC Class I	0.0039	4	481	104	-0.094	0.046	1000	-1000	-0.065	-1000
Canonical NF-kappaB pathway	0.0029	3	153	39	-0.021	0.077	1000	-1000	-0.072	-1000
a4b1 and a4b7 Integrin signaling	0.0029	3	18	5	-0.009	-0.002	1000	-1000	-0.035	-1000
Arf6 downstream pathway	0.0029	3	129	43	-0.01	0.021	1000	-1000	-0.049	-1000
IFN-gamma pathway	0.0029	3	237	68	-0.07	0.075	1000	-1000	-0.094	-1000
ceramide signaling pathway	0.0029	3	192	49	-0.028	0.053	1000	-1000	-0.051	-1000
Insulin-mediated glucose transport	0.0019	2	83	32	-0.13	0.032	1000	-1000	-0.057	-1000
Paxillin-dependent events mediated by a4b1	0.0019	2	91	36	-0.011	0.022	1000	-1000	-0.067	-1000
TCGA08_p53	0.0000	0	0	7	-0.024	0.017	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	7	27	-0.001	0.029	1000	-1000	-0.05	-1000
Arf1 pathway	0.0000	0	23	54	-0.001	0.025	1000	-1000	-0.038	-1000
Alternative NF-kappaB pathway	0.0000	0	1	13	-0.003	0	1000	-1000	-0.057	-1000
Total	NA	7693	457762	7203	-31	-990	131000	-131000	-8.6	-131000

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

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.16	0.22	-10000	0	-0.39	472	472
CRKL	-0.17	0.23	-10000	0	-0.41	472	472
HRAS	-0.16	0.18	-10000	0	-0.46	60	60
mol:PIP3	-0.17	0.21	-10000	0	-0.4	474	474
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.18	0.24	-10000	0	-0.44	473	473
FOXO3	-0.15	0.21	-10000	0	-0.37	471	471
AKT1	-0.16	0.22	-10000	0	-0.41	472	472
BAD	-0.15	0.21	-10000	0	-0.37	471	471
megakaryocyte differentiation	-0.18	0.24	-10000	0	-0.43	474	474
GSK3B	-0.15	0.21	-10000	0	-0.37	471	471
RAF1	-0.092	0.17	-10000	0	-0.4	39	39
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	473	473
STAT1	-0.45	0.56	-10000	0	-1	483	483
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.36	60	60
cell proliferation	-0.18	0.24	-10000	0	-0.44	474	474
PIK3CA	0	0.009	-10000	0	-0.29	1	1
TEC	-0.002	0.043	-10000	0	-0.8	3	3
RPS6KB1	-0.18	0.24	-10000	0	-0.44	473	473
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.36	60	60
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	473	473
MAPK3	-0.054	0.13	-10000	0	-0.32	21	21
STAP1	-0.2	0.24	-10000	0	-0.45	475	475
GRAP2	-0.015	0.11	-10000	0	-0.73	21	21
JAK2	-0.4	0.44	-10000	0	-0.87	483	483
STAT1 (dimer)	-0.44	0.55	-10000	0	-1	483	483
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	473	473
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	473	473
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.34	-10000	0	-0.62	475	475
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.36	470	470
PI3K	-0.19	0.21	-10000	0	-0.41	477	477
PTEN	-0.002	0.035	-10000	0	-0.8	2	2
SCF/KIT/EPO/EPOR	-0.56	0.7	-10000	0	-1.3	471	471
MAPK8	-0.19	0.24	-10000	0	-0.45	474	474
STAT3 (dimer)	-0.18	0.23	-10000	0	-0.43	473	473
positive regulation of transcription	-0.041	0.11	-10000	0	-0.26	21	21
mol:GDP	-0.17	0.18	-10000	0	-0.36	463	463
PIK3C2B	-0.18	0.24	-10000	0	-0.44	473	473
CBL/CRKL	-0.17	0.19	-10000	0	-0.38	471	471
FER	-0.19	0.24	-10000	0	-0.44	478	478
SH2B3	-0.18	0.24	-10000	0	-0.44	473	473
PDPK1	-0.15	0.2	-10000	0	-0.36	473	473
SNAI2	-0.19	0.25	-10000	0	-0.45	475	475
positive regulation of cell proliferation	-0.32	0.41	-10000	0	-0.75	483	483
KITLG	0.001	0.07	-10000	0	-0.7	8	8
cell motility	-0.32	0.41	-10000	0	-0.75	483	483
PTPN6	0.015	0.021	-10000	0	-0.3	1	1
EPOR	-0.096	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	485	485
SOCS1	-0.005	0.042	-10000	0	-0.8	1	1
cell migration	0.19	0.24	0.44	481	-10000	0	481
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.044	0.11	-10000	0	-0.3	171	171
VAV1	-0.003	0.045	-10000	0	-0.6	5	5
GRB10	-0.18	0.24	-10000	0	-0.44	473	473
PTPN11	0.013	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.23	-10000	0	-0.47	478	478
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.064	0.14	-10000	0	-0.35	22	22
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.73	-10000	0	-1.4	469	469
MAP2K2	-0.064	0.14	-10000	0	-0.35	22	22
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	471	471
STAT5A	-0.27	0.35	-10000	0	-0.64	485	485
GRB2	0	0.009	-10000	0	-0.29	1	1
response to radiation	-0.18	0.24	-10000	0	-0.44	475	475
SHC/GRAP2	-0.011	0.081	-10000	0	-0.61	18	18
PTPRO	-0.18	0.24	-10000	0	-0.44	474	474
SH2B2	-0.19	0.24	-10000	0	-0.45	473	473
DOK1	-0.001	0.018	-10000	0	-0.29	4	4
MATK	-0.19	0.25	-10000	0	-0.45	481	481
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.13	0.3	-10000	0	-1.5	36	36

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.22	0.36	0.8	280	-10000	0	280
PI3K Class IB/PDE3B	-0.22	0.36	-10000	0	-0.8	280	280
PDE3B	-0.22	0.36	-10000	0	-0.8	280	280

×

EGFR-dependent Endothelin signaling events

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
HRAS	-0.003	0.027	-9999	-0.29	9	9
EGFR	-0.29	0.39	-9999	-0.8	383	383
EGF/EGFR	-0.28	0.31	-9999	-0.55	530	530
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.25	0.27	-9999	-0.5	519	519
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.001	0.025	-9999	-0.8	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.16	0.32	-9999	-0.8	202	202
EGF/EGFR dimer/SHC	-0.29	0.31	-9999	-0.58	519	519
mol:GDP	-0.25	0.26	-9999	-0.49	519	519
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.062	0.21	-9999	-0.8	81	81
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.23	0.25	-9999	-0.46	519	519
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.23	0.25	-9999	-0.46	519	519
FRAP1	-0.24	0.26	-9999	-0.48	519	519
EGF/EGFR dimer	-0.34	0.35	-9999	-0.67	519	519
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
ETA receptor/Endothelin-1	-0.048	0.16	-9999	-0.61	81	81

×

Reelin signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.006	0.034	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.8	31	31
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.035	-9999	-0.8	2	2
ITGA3	-0.004	0.052	-9999	-0.58	7	7
RELN/VLDLR/Fyn	-0.33	0.28	-9999	-0.55	631	631
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.005	0.047	-9999	-0.45	11	11
AKT1	-0.2	0.17	-9999	-0.33	636	636
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.068	-9999	-0.29	61	61
RELN/LRP8/DAB1	-0.32	0.25	-9999	-0.52	624	624
LRPAP1/LRP8	-0.02	0.057	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.3	0.24	-9999	-0.48	624	624
DAB1/alpha3/beta1 Integrin	-0.28	0.23	-9999	-0.5	265	265
long-term memory	-0.36	0.3	-9999	-0.54	677	677
DAB1/LIS1	-0.29	0.23	-9999	-0.46	631	631
DAB1/CRLK/C3G	-0.28	0.22	-9999	-0.58	139	139
PIK3CA	0	0.009	-9999	-0.29	1	1
DAB1/NCK2	-0.29	0.24	-9999	-0.47	631	631
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.094	0.26	-9999	-0.76	129	129
CDK5R1	-0.008	0.048	-9999	-0.29	29	29
RELN	-0.48	0.39	-9999	-0.8	626	626
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
RELN/LRP8/Fyn	-0.33	0.27	-9999	-0.55	623	623
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.34	0.29	-9999	-0.55	644	644
MAPK8	-0.006	0.07	-9999	-0.8	8	8
RELN/VLDLR/DAB1	-0.32	0.26	-9999	-0.52	631	631
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.31	0.26	-9999	-0.5	635	635
RELN/LRP8	-0.33	0.27	-9999	-0.55	623	623
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.33	0.26	-9999	-0.5	660	660
PI3K	-0.006	0.06	-9999	-0.61	10	10
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.039	-9999	-0.61	4	4
RAP1A	-0.26	0.21	-9999	-0.54	139	139
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.048	-9999	-0.46	9	9
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.056	0.2	-9999	-0.79	73	73
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.13	0.11	-9999	-0.48	12	12
neuron adhesion	-0.24	0.2	-9999	-0.51	141	141
LRP8	-0.031	0.089	-9999	-0.29	111	111
GSK3B	-0.17	0.18	-9999	-0.45	66	66
RELN/VLDLR/DAB1/Fyn	-0.3	0.24	-9999	-0.48	631	631
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.22	0.18	-9999	-0.35	636	636
CDK5	-0.002	0.024	-9999	-0.29	7	7
MAPT	-0.047	0.24	-9999	-0.73	115	115
neuron migration	-0.23	0.24	-9999	-0.42	624	624
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.14	0.11	-9999	-0.48	12	12
RELN/VLDLR	-0.32	0.26	-9999	-0.52	631	631

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.41	0.46	-9999	-0.99	294	294
HDAC7	0	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.33	0.31	-9999	-0.77	238	238
SMAD4	-0.001	0.025	-9999	-0.8	1	1
ID2	-0.41	0.46	-9999	-0.99	291	291
AP1	-0.19	0.29	-9999	-0.63	308	308
ABCG2	-0.44	0.5	-9999	-1.1	301	301
HIF1A	-0.052	0.063	-9999	-10000	0	0
TFF3	-0.49	0.52	-9999	-1.1	371	371
GATA2	-0.015	0.14	-9999	-0.63	42	42
AKT1	-0.053	0.08	-9999	-10000	0	0
response to hypoxia	-0.075	0.086	-9999	-0.24	45	45
MCL1	-0.41	0.46	-9999	-0.99	290	290
NDRG1	-0.42	0.46	-9999	-1	292	292
SERPINE1	-0.42	0.46	-9999	-0.99	298	298
FECH	-0.41	0.46	-9999	-0.99	291	291
FURIN	-0.41	0.46	-9999	-0.99	294	294
NCOA2	-0.026	0.17	-9999	-0.8	45	45
EP300	-0.053	0.12	-9999	-0.35	55	55
HMOX1	-0.42	0.46	-9999	-0.99	293	293
BHLHE40	-0.42	0.46	-9999	-0.99	293	293
BHLHE41	-0.42	0.47	-9999	-1	292	292
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.05	0.055	-9999	-0.61	1	1
ENG	-0.035	0.061	-9999	-0.55	1	1
JUN	-0.004	0.066	-9999	-0.8	7	7
RORA	-0.41	0.46	-9999	-0.99	293	293
ABCB1	-0.34	0.55	-9999	-1.4	205	205
TFRC	-0.42	0.46	-9999	-0.99	295	295
CXCR4	-0.42	0.46	-9999	-1	292	292
TF	-0.65	0.57	-9999	-1.1	563	563
CITED2	-0.41	0.46	-9999	-0.99	290	290
HIF1A/ARNT	-0.5	0.52	-9999	-1.1	298	298
LDHA	-0.049	0.047	-9999	-10000	0	0
ETS1	-0.42	0.46	-9999	-1	293	293
PGK1	-0.41	0.46	-9999	-0.99	294	294
NOS2	-0.42	0.46	-9999	-1	293	293
ITGB2	-0.42	0.46	-9999	-0.99	293	293
ALDOA	-0.42	0.46	-9999	-0.99	294	294
Cbp/p300/CITED2	-0.43	0.44	-9999	-1	267	267
FOS	-0.24	0.37	-9999	-0.8	307	307
HK2	-0.42	0.46	-9999	-1	289	289
SP1	0.012	0.024	-9999	-10000	0	0
GCK	-0.14	0.37	-9999	-1.6	56	56
HK1	-0.41	0.46	-9999	-0.99	293	293
NPM1	-0.41	0.46	-9999	-0.99	293	293
EGLN1	-0.41	0.46	-9999	-0.99	293	293
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.41	0.46	-9999	-0.99	291	291
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.19	0.41	-9999	-1.1	139	139
IGFBP1	-0.51	0.53	-9999	-1.1	369	369
VEGFA	-0.25	0.31	-9999	-0.75	120	120
HIF1A/JAB1	-0.029	0.026	-9999	-10000	0	0
CP	-0.53	0.55	-9999	-1.1	397	397
CXCL12	-0.44	0.5	-9999	-1.1	306	306
COPS5	0.008	0.011	-9999	-0.29	1	1
SMAD3/SMAD4	-0.001	0.019	-9999	-0.61	1	1
BNIP3	-0.42	0.46	-9999	-0.99	293	293
EGLN3	-0.42	0.47	-9999	-1	297	297
CA9	-0.46	0.48	-9999	-1	321	321
TERT	-0.43	0.47	-9999	-1	297	297
ENO1	-0.41	0.46	-9999	-0.99	291	291
PFKL	-0.41	0.46	-9999	-0.99	293	293
NCOA1	-0.001	0.025	-9999	-0.8	1	1
ADM	-0.44	0.49	-9999	-1	314	314
ARNT	-0.052	0.063	-9999	-10000	0	0
HNF4A	-0.002	0.043	-9999	-0.32	3	3
ADFP	-0.42	0.46	-9999	-1	295	295
SLC2A1	-0.25	0.32	-9999	-0.75	128	128
LEP	-0.76	0.52	-9999	-1.1	629	629
HIF1A/ARNT/Cbp/p300	-0.34	0.33	-9999	-0.8	239	239
EPO	-0.24	0.27	-9999	-0.85	45	45
CREBBP	-0.053	0.12	-9999	-0.35	55	55
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.31	-9999	-0.78	222	222
PFKFB3	-0.42	0.47	-9999	-1	291	291
NT5E	-0.42	0.47	-9999	-1	293	293

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.62	-9999	-1.3	350	350
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.082	0.15	-9999	-0.4	13	13
ATF2/c-Jun	-0.053	0.15	-9999	-0.79	14	14
MAPK11	-0.084	0.16	-9999	-0.47	19	19
MITF	-0.093	0.2	-9999	-0.36	357	357
MAPKAPK5	-0.089	0.19	-9999	-0.35	353	353
KRT8	-0.095	0.19	-9999	-0.36	354	354
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-0.29	1	1
p38alpha-beta/CK2	-0.12	0.24	-9999	-0.45	353	353
CEBPB	-0.089	0.19	-9999	-0.35	353	353
SLC9A1	-0.089	0.19	-9999	-0.35	353	353
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.082	0.19	-9999	-0.34	354	354
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.56	16	16
JUN	-0.051	0.15	-9999	-0.78	14	14
PPARGC1A	-0.21	0.37	-9999	-0.58	431	431
USF1	-0.089	0.19	-9999	-0.35	353	353
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.38	16	16
NOS2	-0.093	0.22	-9999	-0.82	18	18
DDIT3	-0.089	0.19	-9999	-0.35	353	353
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.074	0.17	-9999	-0.43	50	50
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.56	16	16
CREB1	-0.094	0.2	-9999	-0.37	353	353
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.51	15	15
RPS6KA4	-0.089	0.19	-9999	-0.49	19	19
PLA2G4A	-0.13	0.27	-9999	-0.73	126	126
GDI1	-0.089	0.19	-9999	-0.35	353	353
TP53	-0.12	0.24	-9999	-0.44	353	353
RPS6KA5	-0.095	0.2	-9999	-0.36	361	361
ESR1	-0.18	0.25	-9999	-0.42	483	483
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.19	-9999	-0.35	353	353
MEF2A	-0.09	0.19	-9999	-0.35	353	353
EIF4EBP1	-0.094	0.2	-9999	-0.37	353	353
KRT19	-0.1	0.2	-9999	-0.37	357	357
ELK4	-0.089	0.19	-9999	-0.35	353	353
ATF6	-0.089	0.19	-9999	-0.35	353	353
ATF1	-0.094	0.2	-9999	-0.37	353	353
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.56	17	17
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.53	19	19

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.24	0.28	-9999	-0.75	135	135
PCK1	-1.1	0.7	-9999	-1.6	650	650
HNF4A	-0.25	0.28	-9999	-0.86	78	78
KCNJ11	-0.28	0.31	-9999	-0.84	143	143
AKT1	-0.15	0.14	-9999	-0.38	65	65
response to starvation	-0.001	0.007	-9999	-10000	0	0
DLK1	-0.5	0.56	-9999	-1.2	350	350
NKX2-1	-0.054	0.15	-9999	-0.55	2	2
ACADM	-0.25	0.28	-9999	-0.78	130	130
TAT	-1.2	0.68	-9999	-1.6	751	751
CEBPB	0.005	0.006	-9999	-10000	0	0
CEBPA	-0.001	0.075	-9999	-0.8	9	9
TTR	-0.46	0.29	-9999	-0.74	387	387
PKLR	-0.25	0.28	-9999	-0.76	131	131
APOA1	-0.3	0.3	-9999	-0.89	98	98
CPT1C	-0.25	0.28	-9999	-0.78	125	125
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.7	418	418
FOXF1	-0.004	0.056	-9999	-0.8	4	4
NF1	0.017	0.025	-9999	-0.8	1	1
HNF1A (dimer)	0.003	0.025	-9999	-0.29	5	5
CPT1A	-0.24	0.28	-9999	-0.76	129	129
HMGCS1	-0.24	0.28	-9999	-0.78	116	116
NR3C1	-0.11	0.13	-9999	-0.53	37	37
CPT1B	-0.24	0.28	-9999	-0.79	117	117
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.007	-9999	-10000	0	0
GCK	-0.28	0.36	-9999	-0.92	163	163
CREB1	-0.059	0.066	-9999	-10000	0	0
IGFBP1	-0.45	0.6	-9999	-1.5	236	236
PDX1	-0.13	0.15	-9999	-0.5	14	14
UCP2	-0.24	0.28	-9999	-0.77	120	120
ALDOB	-0.27	0.3	-9999	-0.81	140	140
AFP	-0.7	0.61	-9999	-1.2	504	504
BDH1	-0.24	0.28	-9999	-0.76	135	135
HADH	-0.26	0.3	-9999	-0.82	121	121
F2	-0.3	0.3	-9999	-0.84	126	126
HNF1A	0.003	0.025	-9999	-0.29	5	5
G6PC	-0.2	0.12	-9999	-0.64	8	8
SLC2A2	-0.16	0.17	-9999	-0.52	11	11
INS	0.024	0.066	-9999	-10000	0	0
FOXA1	-0.25	0.28	-9999	-0.59	289	289
FOXA3	-0.43	0.23	-9999	-0.53	754	754
FOXA2	-0.32	0.34	-9999	-0.82	213	213
ABCC8	-0.35	0.44	-9999	-1.1	197	197
ALB	-0.96	0.64	-9999	-1.4	682	682

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.019	-10000	0	-0.61	1	1
Necdin/E2F1	-0.082	0.15	-10000	0	-0.69	41	41
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.15	0.22	-10000	0	-0.46	334	334
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.32	-10000	0	-0.63	410	410
NT-4/5 (dimer)/p75(NTR)	-0.39	0.42	-10000	0	-0.77	525	525
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	-0.15	0.22	-10000	0	-0.46	337	337
IKBKG	0	0	-10000	0	-10000	0	0
BDNF	-0.07	0.22	-10000	0	-0.8	81	81
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.25	-10000	0	-0.56	325	325
FURIN	-0.001	0.013	-10000	0	-0.29	2	2
proBDNF (dimer)/p75(NTR)/Sortilin	-0.21	0.29	-10000	0	-0.58	370	370
LINGO1	-0.069	0.12	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	-0.001	0.025	-10000	0	-0.8	1	1
proBDNF (dimer)	-0.07	0.22	-10000	0	-0.8	81	81
NTRK1	-0.01	0.066	-10000	0	-0.36	29	29
RTN4R	-0.011	0.056	-10000	0	-10000	0	0
neuron apoptosis	-0.14	0.27	-10000	0	-0.5	325	325
IRAK1	-0.001	0.018	-10000	0	-0.29	4	4
SHC1	-0.16	0.27	-10000	0	-0.54	332	332
ARHGDIA	0	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.014	-10000	0	-0.45	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.16	0.23	-10000	0	-0.49	332	332
MAGEH1	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.18	0.26	-10000	0	-0.53	346	346
Mammalian IAPs/DIABLO	-0.006	0.046	-10000	0	-0.48	9	9
proNGF (dimer)	-0.014	0.098	-10000	0	-0.64	22	22
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
APP	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.28	0.38	-10000	0	-0.8	363	363
ZNF274	0	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.15	0.22	-10000	0	-0.46	332	332
NGF	-0.014	0.099	-10000	0	-0.64	22	22
cell cycle arrest	-0.12	0.23	-10000	0	-0.45	332	332
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.11	0.16	-10000	0	-0.33	332	332
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.34	0.37	-10000	0	-0.68	525	525
NCSTN	0	0	-10000	0	-10000	0	0
mol:GTP	-0.18	0.26	-10000	0	-0.55	332	332
PSENEN	0	0.009	-10000	0	-0.29	1	1
mol:ceramide	-0.14	0.24	-10000	0	-0.49	332	332
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.085	0.13	-10000	0	-0.48	13	13
p75(NTR)/beta APP	-0.19	0.28	-10000	0	-0.61	325	325
BEX1	-0.15	0.28	-10000	0	-0.52	302	302
mol:GDP	-0.16	0.27	-10000	0	-0.55	332	332
NGF (dimer)	-0.082	0.18	-10000	0	-0.5	162	162
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.23	-10000	0	-0.52	325	325
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
RAC1/GTP	-0.15	0.22	-10000	0	-0.47	332	332
MYD88	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.18	0.26	-10000	0	-0.56	332	332
RHOB	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.058	0.086	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.29	-10000	0	-0.76	176	176
TP53	-0.17	0.24	-10000	0	-0.46	370	370
PRDM4	-0.14	0.25	-10000	0	-0.49	332	332
BDNF (dimer)	-0.17	0.23	-10000	0	-0.58	216	216
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SORT1	-0.001	0.025	-10000	0	-0.8	1	1
activation of caspase activity	-0.15	0.22	-10000	0	-0.46	334	334
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.16	0.23	-10000	0	-0.49	332	332
RHOC	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.16	0.27	-10000	0	-0.5	338	338
DIABLO	0	0	-10000	0	-10000	0	0
SMPD2	-0.14	0.25	-10000	0	-0.49	332	332
APH1B	-0.001	0.025	-10000	0	-0.8	1	1
APH1A	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.18	0.26	-10000	0	-0.54	332	332
PSEN1	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.28	0.36	-10000	0	-0.7	421	421
MAPK8	-0.11	0.24	-10000	0	-0.44	325	325
MAPK9	-0.11	0.24	-10000	0	-0.44	325	325
APAF1	0	0	-10000	0	-10000	0	0
NTF3	-0.13	0.29	-10000	0	-0.76	176	176
NTF4	-0.28	0.38	-10000	0	-0.8	363	363
NDN	-0.032	0.16	-10000	0	-0.8	41	41
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.14	0.21	-10000	0	-0.44	332	332
p75 CTF/Sortilin/TRAF6/NRIF	0	0.015	-10000	0	-0.48	1	1
RhoA-B-C/GTP	-0.18	0.26	-10000	0	-0.55	332	332
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.18	0.25	-10000	0	-0.5	370	370
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.19	0.27	-10000	0	-0.53	370	370
PRKACB	-0.016	0.074	-10000	0	-0.32	51	51
proBDNF (dimer)/p75 ECD	-0.052	0.17	-10000	0	-0.61	81	81
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.08	-10000	0	-0.8	9	9
BIRC2	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.13	0.26	0.24	72	-0.47	333	405
BAD	-0.12	0.24	-10000	0	-0.45	327	327
RIPK2	-0.001	0.02	-10000	0	-0.29	5	5
NGFR	-0.25	0.37	-10000	0	-0.8	325	325
CYCS	-0.15	0.22	-10000	0	-0.46	332	332
ADAM17	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.16	0.23	-10000	0	-0.49	332	332
BCL2L11	-0.12	0.24	-10000	0	-0.45	327	327
BDNF (dimer)/p75(NTR)	-0.24	0.33	-10000	0	-0.66	370	370
PI3K	-0.16	0.24	-10000	0	-0.5	337	337
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.16	0.23	-10000	0	-0.49	332	332
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
NGF (dimer)/p75(NTR)	-0.2	0.3	-10000	0	-0.63	332	332
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.16	0.23	-10000	0	-0.5	332	332
TRAF6	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
PLG	-0.001	0.02	-10000	0	-0.29	5	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.19	0.27	-10000	0	-0.53	377	377
SQSTM1	0	0.009	-10000	0	-0.29	1	1
NGFRAP1	-0.002	0.035	-10000	0	-0.8	2	2
CASP3	-0.11	0.23	-10000	0	-0.42	327	327
E2F1	-0.092	0.14	-10000	0	-0.29	330	330
CASP9	0	0	-10000	0	-10000	0	0
IKK complex	-0.067	0.12	-10000	0	-0.58	20	20
NGF (dimer)/TRKA	-0.017	0.088	-10000	0	-0.62	19	19
MMP7	-0.12	0.28	-10000	0	-0.72	178	178
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.15	0.22	-10000	0	-0.46	332	332
MMP3	-0.12	0.16	-10000	0	-0.31	400	400
APAF-1/Caspase 9	-0.11	0.16	-10000	0	-0.66	15	15

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.023	0.078	0.34	8	-10000	0	8
SMARCC2	0.012	0.01	-10000	0	-10000	0	0
SMARCC1	0.012	0.01	-10000	0	-10000	0	0
TBX21	-0.14	0.26	-10000	0	-0.85	77	77
SUMO2	0	0.01	-10000	0	-0.29	1	1
STAT1 (dimer)	0.014	0.041	-10000	0	-0.28	19	19
FKBP4	-0.003	0.027	-10000	0	-0.29	9	9
FKBP5	-0.013	0.098	-10000	0	-0.68	20	20
GR alpha/HSP90/FKBP51/HSP90	0.11	0.13	0.34	63	-0.42	14	77
PRL	-0.089	0.12	-10000	0	-0.5	4	4
cortisol/GR alpha (dimer)/TIF2	0.27	0.29	0.53	473	-0.55	28	501
RELA	-0.039	0.083	-10000	0	-0.3	1	1
FGG	0.24	0.22	0.49	290	-0.5	1	291
GR beta/TIF2	0.11	0.19	0.33	144	-0.57	47	191
IFNG	-0.43	0.35	-10000	0	-0.79	404	404
apoptosis	-0.28	0.3	0.59	3	-0.67	266	269
CREB1	-0.009	0.03	-10000	0	-10000	0	0
histone acetylation	0.021	0.14	0.39	43	-0.37	38	81
BGLAP	-0.1	0.15	-10000	0	-0.52	20	20
GR/PKAc	0.12	0.12	0.32	72	-0.46	3	75
NF kappa B1 p50/RelA	-0.066	0.15	-10000	0	-0.42	34	34
SMARCD1	0.012	0.01	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.25	276	-10000	0	276
GATA3	-0.026	0.16	-10000	0	-0.64	54	54
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.041	0.11	-10000	0	-0.6	7	7
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.27	0.56	3	-0.62	171	174
CSN2	0.2	0.18	0.41	242	-10000	0	242
BRG1/BAF155/BAF170/BAF60A	-0.002	0.032	-10000	0	-0.46	5	5
NFATC1	0	0.044	-10000	0	-0.8	3	3
POU2F1	0.007	0.013	-10000	0	-0.29	1	1
CDKN1A	0.046	0.074	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.008	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.5	31	31
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.34	47	-0.45	6	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.37	0.43	0.54	3	-0.9	361	364
JUN	-0.32	0.29	-10000	0	-0.58	493	493
IL4	-0.13	0.16	-10000	0	-0.56	23	23
CDK5R1	-0.008	0.049	-10000	0	-0.3	29	29
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.42	0.41	-10000	0	-0.74	569	569
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.35	41	-0.48	2	43
cortisol/GR alpha (monomer)	0.35	0.32	0.63	500	-0.44	2	502
NCOA2	-0.035	0.16	-10000	0	-0.8	45	45
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.28	0.38	-10000	0	-0.87	307	307
AP-1/NFAT1-c-4	-0.66	0.52	-10000	0	-1	654	654
AFP	-0.62	0.7	-10000	0	-1.6	360	360
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.42	189	-10000	0	189
TP53	0.031	0.024	-10000	0	-0.5	2	2
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.84	0.8	-10000	0	-1.6	517	517
KRT14	-0.83	0.77	-10000	0	-1.6	548	548
TBP	0.019	0.005	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.28	413	-10000	0	413
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.67	0.52	-10000	0	-1	655	655
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.13	0.29	-10000	0	-0.81	162	162
MAPK11	-0.002	0.044	-10000	0	-0.81	3	3
KRT5	-0.94	0.81	-10000	0	-1.7	560	560
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.011	0.026	-10000	0	-0.8	1	1
STAT1	0.014	0.041	-10000	0	-0.28	19	19
CGA	-0.16	0.18	-10000	0	-0.48	134	134
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.18	0.38	488	-10000	0	488
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.18	0.25	-10000	0	-0.56	230	230
NFKB1	-0.039	0.083	-10000	0	-10000	0	0
MAPK8	-0.24	0.22	-10000	0	-0.44	447	447
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.3	0.32	0.59	3	-0.72	266	269
BAX	0.048	0.032	-10000	0	-10000	0	0
POMC	-0.19	0.3	-10000	0	-0.9	90	90
EP300	0.14	0.14	0.28	426	-10000	0	426
cortisol/GR alpha (dimer)/p53	0.31	0.26	0.56	456	-10000	0	456
proteasomal ubiquitin-dependent protein catabolic process	0.087	0.079	0.24	62	-10000	0	62
SGK1	0.23	0.2	-10000	0	-1.2	6	6
IL13	-0.32	0.28	-10000	0	-0.68	246	246
IL6	-0.5	0.63	-10000	0	-1.3	388	388
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.27	0.22	-10000	0	-0.75	54	54
IL2	-0.42	0.35	-10000	0	-0.75	468	468
CDK5	-0.002	0.024	-10000	0	-0.3	7	7
PRKACB	-0.016	0.074	-10000	0	-0.32	51	51
HSP90AA1	0	0.009	-10000	0	-10000	0	0
IL8	-0.2	0.3	-10000	0	-0.67	203	203
CDK5R1/CDK5	-0.007	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.058	0.097	-10000	0	-0.51	7	7
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.52	448	-0.48	1	449
SMARCA4	0.012	0.013	-10000	0	-0.29	1	1
chromatin remodeling	0.2	0.16	0.37	362	-0.34	1	363
NF kappa B1 p50/RelA/Cbp	0.061	0.17	0.34	90	-0.45	2	92
JUN (dimer)	-0.32	0.29	-10000	0	-0.57	495	495
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.14	0.25	-10000	0	-0.77	90	90
NR3C1	0.2	0.2	0.44	294	-0.48	7	301
NR4A1	-0.053	0.23	-10000	0	-0.74	97	97
TIF2/SUV420H1	-0.027	0.12	-10000	0	-0.61	45	45
MAPKKK cascade	-0.28	0.3	0.59	3	-0.67	266	269
cortisol/GR alpha (dimer)/Src-1	0.3	0.26	0.53	496	-10000	0	496
PBX1	0.005	0.039	-10000	0	-0.8	2	2
POU1F1	0.003	0.015	-10000	0	-0.28	2	2
SELE	-0.23	0.36	-10000	0	-0.75	229	229
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.37	361	-0.34	1	362
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.52	448	-0.48	1	449
mol:cortisol	0.2	0.2	0.36	520	-10000	0	520
MMP1	-0.22	0.11	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.12	0.41	-10000	0	-0.91	221	221
NCK1/PAK1/Dok-R	-0.09	0.17	-10000	0	-0.42	221	221
NCK1/Dok-R	-0.24	0.47	-10000	0	-1.1	221	221
PIK3CA	0.003	0.011	-10000	0	-0.29	1	1
mol:beta2-estradiol	0.037	0.099	0.24	196	-10000	0	196
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.003	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.038	0.11	0.25	185	-0.31	8	193
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.22	0.44	-10000	0	-1.1	221	221
FN1	-0.12	0.14	-10000	0	-0.29	414	414
PLD2	-0.19	0.52	-10000	0	-1.2	221	221
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.22	-10000	0	-0.47	221	221
ELK1	-0.16	0.46	-10000	0	-1	221	221
GRB7	-0.021	0.077	-10000	0	-0.3	72	72
PAK1	-0.007	0.044	-10000	0	-0.29	24	24
Tie2/Ang1/alpha5/beta1 Integrin	-0.2	0.49	-10000	0	-1.1	221	221
CDKN1A	-0.063	0.28	-10000	0	-0.61	156	156
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.24	0.47	-10000	0	-1.1	221	221
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.067	0.31	-10000	0	-0.66	221	221
PLG	-0.2	0.52	-10000	0	-1.2	221	221
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.18	0.37	-10000	0	-0.88	221	221
GRB2	0	0.009	-10000	0	-0.29	1	1
PIK3R1	-0.002	0.08	-10000	0	-0.81	10	10
ANGPT2	-0.11	0.27	-10000	0	-0.75	108	108
BMX	-0.37	0.59	-10000	0	-1.4	224	224
ANGPT1	-0.24	0.57	-10000	0	-1.4	196	196
tube development	-0.08	0.31	-10000	0	-0.64	220	220
ANGPT4	-0.24	0.37	-10000	0	-0.8	313	313
response to hypoxia	-0.01	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.28	0.54	-10000	0	-1.3	221	221
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.32	0.39	-10000	0	-0.8	416	416
STAT5A (dimer)	-0.096	0.35	-10000	0	-0.78	180	180
mol:L-citrulline	-0.067	0.31	-10000	0	-0.66	221	221
AGTR1	-0.2	0.34	-10000	0	-0.7	308	308
MAPK14	-0.18	0.5	-10000	0	-1.1	221	221
Tie2/SHP2	-0.098	0.28	-10000	0	-1.3	48	48
TEK	-0.1	0.32	-10000	0	-1.5	48	48
RPS6KB1	-0.12	0.4	-10000	0	-0.87	221	221
Angiotensin II/AT1	-0.16	0.26	-10000	0	-0.55	293	293
Tie2/Ang1/GRB2	-0.26	0.52	-10000	0	-1.2	221	221
MAPK3	-0.17	0.48	-10000	0	-1.1	221	221
MAPK1	-0.17	0.48	-10000	0	-1.1	221	221
Tie2/Ang1/GRB7	-0.26	0.52	-10000	0	-1.2	222	222
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.2	0.53	-10000	0	-1.2	221	221
PI3K	-0.16	0.48	-10000	0	-1.1	221	221
FES	-0.18	0.5	-10000	0	-1.1	221	221
Crk/Dok-R	-0.24	0.47	-10000	0	-1.1	221	221
Tie2/Ang1/ABIN2	-0.26	0.52	-10000	0	-1.2	221	221
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.1	0.37	-10000	0	-0.8	221	221
STAT5A	-0.006	0.07	-10000	0	-0.8	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.12	0.4	-10000	0	-0.87	221	221
Tie2/Ang2	-0.13	0.41	-10000	0	-0.93	186	186
Tie2/Ang1	-0.22	0.58	-10000	0	-1.3	221	221
FOXO1	-0.098	0.38	-10000	0	-0.81	222	222
ELF1	0.014	0.022	-10000	0	-10000	0	0
ELF2	-0.19	0.52	-10000	0	-1.2	221	221
mol:Choline	-0.18	0.5	-10000	0	-1.1	221	221
cell migration	-0.04	0.1	-10000	0	-0.24	221	221
FYN	-0.098	0.35	-10000	0	-0.77	186	186
DOK2	-0.003	0.047	-10000	0	-0.8	3	3
negative regulation of cell cycle	-0.053	0.25	-10000	0	-0.54	177	177
ETS1	-0.028	0.11	-10000	0	-0.98	5	5
PXN	-0.079	0.33	-10000	0	-0.71	221	221
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.086	0.35	-10000	0	-0.75	221	221
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.041	0.14	-10000	0	-0.78	19	19
MAPKKK cascade	-0.18	0.5	-10000	0	-1.1	221	221
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.24	0.53	-10000	0	-1.2	221	221
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.054	0.28	-10000	0	-0.59	221	221
mol:Phosphatidic acid	-0.18	0.5	-10000	0	-1.1	221	221
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.067	0.31	-10000	0	-0.66	221	221
Rac1/GTP	-0.17	0.33	-10000	0	-0.81	221	221
MMP2	-0.2	0.53	-10000	0	-1.2	222	222

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.8	31	31
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.33	0.27	-9999	-0.55	623	623
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-0.29	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.29	0.26	-9999	-0.5	623	623
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.068	-9999	-0.29	61	61
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.016	0.094	-9999	-0.43	39	39
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.009	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.02	0.057	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.008	0.048	-9999	-0.29	29	29
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.043	0.1	-9999	-0.29	155	155
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.34	0.28	-9999	-0.56	631	631
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.24	0.19	-9999	-0.46	178	178
MAP1B	-0.007	0.051	-9999	-0.38	19	19
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.26	0.21	-9999	-0.44	623	623
RELN	-0.48	0.39	-9999	-0.8	626	626
PAFAH/LIS1	-0.009	0.059	-9999	-0.53	11	11
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-9999	-0.44	5	5
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.21	0.17	-9999	-0.34	634	634
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.26	0.2	-9999	-0.44	393	393
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.034	0.093	-9999	-0.29	122	122
PAFAH1B2	-0.004	0.056	-9999	-0.8	5	5
MAP1B/LIS1/Dynein heavy chain	-0.004	0.032	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.22	0.18	-9999	-0.46	96	96
LRP8	-0.031	0.089	-9999	-0.29	111	111
NDEL1/Katanin 60	-0.24	0.19	-9999	-0.46	179	179
P39/CDK5	-0.28	0.22	-9999	-0.46	623	623
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.26	0.24	-9999	-0.46	623	623
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.29	0.24	-9999	-0.48	631	631
RELN/VLDLR	-0.32	0.26	-9999	-0.52	631	631
CDC42	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.23	0.43	-9999	-0.93	154	154
PLK1	-0.085	0.1	-9999	-10000	0	0
BIRC5	-0.097	0.1	-9999	-10000	0	0
HSPA1B	-0.23	0.43	-9999	-0.91	168	168
MAP2K1	0.008	0.029	-9999	-10000	0	0
BRCA2	-0.23	0.43	-9999	-0.92	170	170
FOXM1	-0.28	0.51	-9999	-1	215	215
XRCC1	-0.23	0.43	-9999	-0.91	172	172
FOXM1B/p19	-0.28	0.41	-9999	-0.9	235	235
Cyclin D1/CDK4	-0.22	0.4	-9999	-0.89	143	143
CDC2	-0.25	0.45	-9999	-0.91	215	215
TGFA	-0.22	0.42	-9999	-0.91	152	152
SKP2	-0.23	0.43	-9999	-0.9	182	182
CCNE1	-0.055	0.12	-9999	-0.3	210	210
CKS1B	-0.23	0.43	-9999	-0.93	155	155
RB1	-0.12	0.12	-9999	-0.89	1	1
FOXM1C/SP1	-0.29	0.44	-9999	-0.96	215	215
AURKB	-0.077	0.11	-9999	-10000	0	0
CENPF	-0.26	0.45	-9999	-0.93	206	206
CDK4	0.007	0.02	-9999	-0.3	3	3
MYC	-0.21	0.41	-9999	-0.84	181	181
CHEK2	0.008	0.033	-9999	-0.31	2	2
ONECUT1	-0.23	0.42	-9999	-0.89	180	180
CDKN2A	-0.037	0.11	-9999	-0.28	169	169
LAMA4	-0.23	0.44	-9999	-0.91	183	183
FOXM1B/HNF6	-0.26	0.48	-9999	-1	179	179
FOS	-0.44	0.67	-9999	-1.3	351	351
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.23	0.43	-9999	-0.91	172	172
response to radiation	-0.007	0.03	-9999	-10000	0	0
CENPB	-0.23	0.43	-9999	-0.91	167	167
CENPA	-0.26	0.45	-9999	-0.93	201	201
NEK2	-0.28	0.44	-9999	-0.95	191	191
HIST1H2BA	-0.24	0.43	-9999	-0.9	182	182
CCNA2	-0.11	0.15	-9999	-0.3	413	413
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.27	0.48	-9999	-1	194	194
CCNB2	-0.26	0.45	-9999	-0.93	204	204
CCNB1	-0.25	0.46	-9999	-0.95	195	195
ETV5	-0.23	0.43	-9999	-0.97	132	132
ESR1	-0.33	0.58	-9999	-1.2	241	241
CCND1	-0.22	0.42	-9999	-0.91	145	145
GSK3A	0.014	0.021	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.081	0.14	-9999	-0.33	182	182
CDK2	0.006	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.009	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.32	0.37	-9999	-0.88	243	243
GAS1	-0.27	0.49	-9999	-1	204	204
MMP2	-0.24	0.44	-9999	-0.96	155	155
RB1/FOXM1C	-0.23	0.44	-9999	-0.91	178	178
CREBBP	0	0	-9999	-10000	0	0

×

Arf6 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.045	-9999	-0.66	4	4
ARNO/beta Arrestin1-2	-0.13	0.19	-9999	-0.44	240	240
EGFR	-0.29	0.39	-9999	-0.8	383	383
EPHA2	-0.005	0.061	-9999	-0.8	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.34	0.35	-9999	-0.67	519	519
ARRB2	-0.054	0.16	-9999	-0.44	143	143
mol:GTP	0.017	0.018	-9999	-0.16	4	4
ARRB1	-0.002	0.036	-9999	-0.63	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.036	0.16	-9999	-0.75	50	50
EGF	-0.16	0.32	-9999	-0.8	202	202
somatostatin receptor activity	0	0	-9999	-0.001	366	366
ARAP2	-0.004	0.056	-9999	-0.8	5	5
mol:GDP	-0.14	0.18	-9999	-0.35	332	332
mol:PI-3-4-5-P3	0	0	-9999	-0.001	317	317
ITGA2B	-0.018	0.078	-9999	-0.8	3	3
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.037	-9999	-0.48	6	6
ADAP1	-0.005	0.05	-9999	-0.43	11	11
KIF13B	-0.002	0.035	-9999	-0.8	2	2
HGF/MET	-0.14	0.28	-9999	-0.66	220	220
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.31	365	365
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.29	0.31	-9999	-0.58	519	519
ADRB2	-0.18	0.34	-9999	-0.8	239	239
receptor agonist activity	0	0	-9999	0	375	375
actin filament binding	0	0	-9999	-0.001	370	370
SRC	0	0.009	-9999	-0.29	1	1
ITGB3	-0.028	0.15	-9999	-0.75	39	39
GNAQ	-0.002	0.035	-9999	-0.8	2	2
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	362	362
ARF6/GDP	-0.014	0.084	-9999	-0.42	17	17
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.47	217	217
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.025	0.096	-9999	-0.5	38	38
ACAP1	-0.019	0.095	-9999	-0.39	49	49
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.091	0.23	-9999	-0.66	143	143
EFNA1	0	0	-9999	-10000	0	0
HGF	-0.053	0.2	-9999	-0.8	68	68
CYTH3	0.01	0.02	-9999	-0.62	1	1
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	382	382
endosomal lumen acidification	0	0	-9999	-0.001	311	311
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.051	0.2	-9999	-0.8	66	66
GNAQ/ARNO	0.004	0.022	-9999	-0.46	2	2
mol:Phosphatidic acid	0	0	-9999	0	2	2
PIP3-E	0	0	-9999	0	402	402
MET	-0.13	0.3	-9999	-0.8	172	172
GNA14	-0.014	0.088	-9999	-0.46	31	31
GNA15	-0.003	0.034	-9999	-0.8	1	1
GIT1	-0.001	0.02	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	365	365
GNA11	-0.002	0.035	-9999	-0.8	2	2
LHCGR	-0.11	0.28	-9999	-0.8	143	143
AGTR1	-0.21	0.34	-9999	-0.7	308	308
desensitization of G-protein coupled receptor protein signaling pathway	-0.091	0.23	-9999	-0.66	143	143
IPCEF1/ARNO	-0.24	0.25	-9999	-0.47	519	519
alphaIIb/beta3 Integrin	-0.033	0.12	-9999	-0.63	38	38

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.075	0.16	-10000	0	-0.39	134	134
NFATC2	-0.057	0.27	-10000	0	-0.77	115	115
NFATC3	-0.056	0.12	-10000	0	-0.31	51	51
CD40LG	-0.38	0.58	-10000	0	-1.1	313	313
ITCH	0.013	0.098	-10000	0	-10000	0	0
CBLB	0.013	0.098	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.25	0.36	-10000	0	-1.2	92	92
JUNB	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.1	-10000	0	-0.34	109	109
T cell anergy	-0.028	0.16	-10000	0	-0.48	109	109
TLE4	-0.031	0.26	-10000	0	-0.69	108	108
Jun/NFAT1-c-4/p21SNFT	-0.31	0.44	-10000	0	-1.1	201	201
AP-1/NFAT1-c-4	-0.52	0.66	-10000	0	-1.4	312	312
IKZF1	-0.02	0.21	-10000	0	-0.63	82	82
T-helper 2 cell differentiation	-0.12	0.3	-10000	0	-0.86	100	100
AP-1/NFAT1	-0.23	0.32	-10000	0	-0.64	353	353
CALM1	-0.019	0.054	-10000	0	-10000	0	0
EGR2	-0.31	0.66	-10000	0	-1.6	171	171
EGR3	-0.4	0.74	-10000	0	-1.6	278	278
NFAT1/FOXP3	-0.12	0.22	-10000	0	-0.65	89	89
EGR1	-0.25	0.37	-10000	0	-0.8	328	328
JUN	-0.004	0.068	-10000	0	-0.81	7	7
EGR4	-0.021	0.075	-10000	0	-0.29	75	75
mol:Ca2+	-0.022	0.063	-10000	0	-10000	0	0
GBP3	-0.024	0.22	-10000	0	-0.62	109	109
FOSL1	-0.011	0.073	-10000	0	-0.8	6	6
NFAT1-c-4/MAF/IRF4	-0.32	0.48	-10000	0	-1.1	202	202
DGKA	-0.018	0.21	-10000	0	-0.59	98	98
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.41	0.53	-10000	0	-1.1	305	305
CTLA4	-0.087	0.24	-10000	0	-0.67	79	79
NFAT1-c-4 (dimer)/EGR1	-0.44	0.58	-10000	0	-1.3	309	309
NFAT1-c-4 (dimer)/EGR4	-0.3	0.46	-10000	0	-0.96	279	279
FOS	-0.24	0.37	-10000	0	-0.82	307	307
IFNG	-0.16	0.27	-10000	0	-0.91	83	83
T cell activation	-0.18	0.35	-10000	0	-0.8	190	190
MAF	-0.001	0.025	-10000	0	-0.8	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.17	0.37	0.92	95	-10000	0	95
TNF	-0.33	0.53	-10000	0	-1.1	286	286
FASLG	-0.38	0.69	-10000	0	-1.3	334	334
TBX21	-0.024	0.16	-10000	0	-0.67	55	55
BATF3	-0.002	0.029	-10000	0	-0.42	4	4
PRKCQ	-0.027	0.17	-10000	0	-0.7	57	57
PTPN1	-0.02	0.21	-10000	0	-0.64	75	75
NFAT1-c-4/ICER1	-0.3	0.45	-10000	0	-0.96	280	280
GATA3	-0.035	0.16	-10000	0	-0.58	66	66
T-helper 1 cell differentiation	-0.15	0.26	-10000	0	-0.88	83	83
IL2RA	-0.24	0.34	-10000	0	-0.99	110	110
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.018	0.21	-10000	0	-0.66	65	65
E2F1	-0.078	0.14	-10000	0	-0.28	330	330
PPARG	-0.19	0.34	-10000	0	-0.8	243	243
SLC3A2	-0.018	0.21	-10000	0	-0.63	78	78
IRF4	-0.072	0.23	-10000	0	-0.8	89	89
PTGS2	-0.48	0.66	-10000	0	-1.3	367	367
CSF2	-0.37	0.56	-10000	0	-1.1	308	308
JunB/Fra1/NFAT1-c-4	-0.29	0.44	-10000	0	-1	200	200
IL4	-0.12	0.32	-10000	0	-0.93	95	95
IL5	-0.37	0.56	-10000	0	-1.1	307	307
IL2	-0.18	0.36	-10000	0	-0.82	186	186
IL3	-0.064	0.065	-10000	0	-10000	0	0
RNF128	-0.052	0.28	-10000	0	-0.86	109	109
NFATC1	-0.17	0.37	-10000	0	-0.93	93	93
CDK4	0.09	0.23	0.62	28	-10000	0	28
PTPRK	-0.023	0.23	-10000	0	-0.66	89	89
IL8	-0.37	0.56	-10000	0	-1.1	316	316
POU2F1	0.001	0.01	-10000	0	-0.29	1	1

×

Aurora B signaling

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.051	0.065	-9999	-10000	0	0
STMN1	-0.11	0.12	-9999	-0.36	78	78
Aurora B/RasGAP/Survivin	-0.18	0.13	-9999	-0.29	473	473
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.15	-9999	-0.33	420	420
BIRC5	-0.21	0.14	-9999	-0.29	743	743
DES	-0.29	0.34	-9999	-0.65	476	476
Aurora C/Aurora B/INCENP	-0.068	0.075	-9999	-0.63	1	1
Aurora B/TACC1	-0.099	0.13	-9999	-0.62	37	37
Aurora B/PP2A	-0.098	0.095	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.008	0.016	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.21	0.17	-9999	-0.36	526	526
Cul3 protein complex	-0.22	0.26	-9999	-0.53	420	420
KIF2C	-0.042	0.032	-9999	-10000	0	0
PEBP1	0.002	0.005	-9999	-10000	0	0
KIF20A	-0.22	0.13	-9999	-0.29	777	777
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.098	0.095	-9999	-10000	0	0
SEPT1	-0.009	0.049	-9999	-0.29	31	31
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.004	0.035	-9999	-0.29	15	15
NSUN2/NPM1/Nucleolin	0.007	0.018	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.002	-9999	-10000	0	0
H3F3B	-0.035	0.043	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-0.29	598	598
AURKC	-0.005	0.042	-9999	-0.32	15	15
CDCA8	-0.098	0.14	-9999	-0.3	354	354
cytokinesis	-0.11	0.077	-9999	-10000	0	0
Aurora B/Septin1	-0.095	0.086	-9999	-10000	0	0
AURKA	-0.14	0.15	-9999	-10000	0	0
INCENP	0.003	0.005	-9999	-10000	0	0
KLHL13	-0.32	0.39	-9999	-0.8	419	419
BUB1	-0.2	0.14	-9999	-0.29	711	711
hSgo1/Aurora B/Survivin	-0.25	0.18	-9999	-0.38	635	635
EVI5	0.008	0.005	-9999	-10000	0	0
RhoA/GTP	-0.1	0.099	-9999	-0.34	16	16
SGOL1	-0.18	0.14	-9999	-0.29	650	650
CENPA	-0.056	0.061	-9999	-10000	0	0
NCAPG	-0.14	0.14	-9999	-0.29	507	507
Aurora B/HC8 Proteasome	-0.098	0.095	-9999	-10000	0	0
NCAPD2	-0.002	0.025	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.098	0.095	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.11	0.14	-9999	-0.29	410	410
NPM1	-0.017	0.023	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.002	0.035	-9999	-0.8	2	2
mitotic prometaphase	-0.006	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.098	0.095	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.11	0.11	-9999	-0.36	41	41
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.017	0.023	-9999	-10000	0	0
MYLK	-0.088	0.15	-9999	-0.47	130	130
KIF23	-0.091	0.14	-9999	-0.29	318	318
VIM	-0.094	0.1	-9999	-0.69	2	2
RACGAP1	-0.011	0.06	-9999	-0.3	45	45
mitosis	0	0	-9999	-10000	0	0
NCL	-0.017	0.023	-9999	-10000	0	0
Chromosomal passenger complex	-0.081	0.076	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.16	0.18	-9999	-0.36	289	289
TACC1	-0.029	0.15	-9999	-0.8	37	37
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Endothelins

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
AKT1	-0.011	0.2	-9999	-0.6	85	85
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.021	0.2	-9999	-0.93	33	33
EDN1	-0.038	0.24	-9999	-0.82	84	84
EDN3	-0.38	0.4	-9999	-0.8	486	486
EDN2	-0.075	0.14	-9999	-0.31	253	253
HRAS/GDP	-0.029	0.21	-9999	-0.52	104	104
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.14	-9999	-0.36	93	93
ADCY4	-0.15	0.29	-9999	-0.57	294	294
ADCY5	-0.28	0.36	-9999	-0.61	491	491
ADCY6	-0.13	0.27	-9999	-0.54	278	278
ADCY7	-0.13	0.27	-9999	-0.54	278	278
ADCY1	-0.15	0.29	-9999	-0.57	293	293
ADCY2	-0.17	0.32	-9999	-0.61	306	306
ADCY3	-0.13	0.27	-9999	-0.54	278	278
ADCY8	-0.14	0.27	-9999	-0.55	278	278
ADCY9	-0.13	0.27	-9999	-0.54	278	278
arachidonic acid secretion	-0.1	0.29	-9999	-0.47	339	339
ETB receptor/Endothelin-1/Gq/GTP	-0.034	0.18	-9999	-0.38	179	179
GNAO1	-0.031	0.13	-9999	-0.48	66	66
HRAS	-0.003	0.027	-9999	-0.29	9	9
ETA receptor/Endothelin-1/G12/GTP	0.037	0.21	-9999	-0.56	85	85
ETA receptor/Endothelin-1/Gs/GTP	-0.091	0.32	-9999	-0.57	278	278
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.02	0.21	-9999	-0.6	85	85
EDNRB	-0.073	0.24	-9999	-0.8	105	105
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.026	0.24	-9999	-0.69	102	102
CYSLTR1	-0.022	0.24	-9999	-0.68	97	97
SLC9A1	0.001	0.1	-9999	-0.3	84	84
mol:GDP	-0.037	0.22	-9999	-0.53	120	120
SLC9A3	-0.053	0.28	-9999	-0.63	174	174
RAF1	-0.083	0.25	-9999	-0.54	156	156
JUN	0.027	0.18	-9999	-0.78	34	34
JAK2	-0.011	0.2	-9999	-0.6	85	85
mol:IP3	-0.028	0.18	-9999	-0.44	107	107
ETA receptor/Endothelin-1	0.034	0.25	-9999	-0.66	95	95
PLCB1	-0.051	0.21	-9999	-0.81	74	74
PLCB2	0.007	0.027	-9999	-0.55	2	2
ETA receptor/Endothelin-3	-0.28	0.32	-9999	-0.62	485	485
FOS	-0.25	0.49	-9999	-0.98	317	317
Gai/GDP	-0.015	0.16	-9999	-0.81	26	26
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	-0.05	0.25	-9999	-0.64	122	122
BCAR1	0.002	0.005	-9999	-10000	0	0
PRKCB1	-0.031	0.17	-9999	-0.42	110	110
GNAQ	0.008	0.037	-9999	-0.81	2	2
GNAZ	-0.007	0.075	-9999	-0.8	9	9
GNAL	-0.19	0.34	-9999	-0.8	244	244
Gs family/GDP	-0.17	0.26	-9999	-0.54	290	290
ETA receptor/Endothelin-1/Gq/GTP	0.017	0.13	-9999	-0.38	68	68
MAPK14	-0.031	0.17	-9999	-0.47	93	93
TRPC6	0.018	0.22	-9999	-1.1	31	31
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.039	0.17	-9999	-0.8	50	50
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.04	0.18	-9999	-0.39	174	174
ETB receptor/Endothelin-2	-0.11	0.21	-9999	-0.66	112	112
ETB receptor/Endothelin-3	-0.34	0.34	-9999	-0.66	540	540
ETB receptor/Endothelin-1	-0.084	0.28	-9999	-0.67	174	174
MAPK3	-0.19	0.41	-9999	-0.78	324	324
MAPK1	-0.19	0.41	-9999	-0.78	324	324
Rac1/GDP	-0.028	0.2	-9999	-0.51	104	104
cAMP biosynthetic process	-0.18	0.3	-9999	-0.6	293	293
MAPK8	0.019	0.19	-9999	-0.74	41	41
SRC	0	0.009	-9999	-0.29	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.048	0.18	-9999	-0.53	86	86
p130Cas/CRK/Src/PYK2	-0.014	0.22	-9999	-0.6	78	78
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.028	0.2	-9999	-0.52	102	102
COL1A2	-0.056	0.26	-9999	-0.69	100	100
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.12	-9999	-0.43	22	22
mol:DAG	-0.029	0.18	-9999	-0.44	107	107
MAP2K2	-0.13	0.32	-9999	-0.57	324	324
MAP2K1	-0.13	0.32	-9999	-0.57	324	324
EDNRA	0.027	0.069	-9999	-0.46	4	4
positive regulation of muscle contraction	-0.012	0.17	-9999	-0.52	85	85
Gq family/GDP	-0.074	0.16	-9999	-0.57	64	64
HRAS/GTP	-0.051	0.21	-9999	-0.47	143	143
PRKCH	-0.023	0.17	-9999	-0.47	85	85
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.035	0.2	-9999	-0.52	104	104
PRKCB	-0.034	0.19	-9999	-0.55	80	80
PRKCE	-0.023	0.17	-9999	-0.5	69	69
PRKCD	-0.024	0.17	-9999	-0.47	85	85
PRKCG	-0.032	0.18	-9999	-0.49	81	81
regulation of vascular smooth muscle contraction	-0.29	0.57	-9999	-1.1	317	317
PRKCQ	-0.046	0.22	-9999	-0.54	119	119
PLA2G4A	-0.12	0.33	-9999	-0.52	339	339
GNA14	-0.004	0.09	-9999	-0.46	31	31
GNA15	0.006	0.036	-9999	-0.35	8	8
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.036	-9999	-0.8	2	2
Rac1/GTP	0.037	0.21	-9999	-0.56	85	85
MMP1	-0.12	0.13	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	366	366
FZD6	-0.007	0.075	-9999	-0.8	9	9
WNT6	-0.17	0.32	-9999	-0.71	247	247
WNT4	-0.022	0.12	-9999	-0.53	42	42
FZD3	-0.009	0.082	-9999	-0.8	11	11
WNT5A	-0.014	0.1	-9999	-0.6	25	25
WNT11	-0.17	0.32	-9999	-0.77	227	227

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.46	0.46	-10000	0	-1.1	221	221
STAT6 (cleaved dimer)	-0.5	0.45	-10000	0	-1	364	364
IGHG1	-0.16	0.16	-10000	0	-0.36	83	83
IGHG3	-0.46	0.44	-10000	0	-0.99	327	327
AKT1	-0.21	0.24	-10000	0	-0.67	79	79
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.2	-10000	0	-0.62	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.25	-10000	0	-0.69	81	81
THY1	-0.46	0.46	-10000	0	-1.1	245	245
MYB	-0.016	0.11	-10000	0	-0.73	22	22
HMGA1	-0.014	0.061	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.69	213	213
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.23	-10000	0	-0.64	61	61
SP1	0.018	0.004	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.024	0.029	-10000	0	-0.78	1	1
STAT6 (dimer)/ETS1	-0.49	0.44	-10000	0	-1	321	321
SOCS1	-0.3	0.31	-10000	0	-0.74	192	192
SOCS3	-0.23	0.26	-10000	0	-0.81	68	68
FCER2	-0.6	0.65	-10000	0	-1.5	327	327
PARP14	0.003	0.018	-10000	0	-0.3	3	3
CCL17	-0.47	0.46	-10000	0	-1.1	230	230
GRB2	0	0.009	-10000	0	-0.29	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.62	24	24
T cell proliferation	-0.46	0.48	-10000	0	-1.1	247	247
IL4R/JAK1	-0.46	0.46	-10000	0	-1.1	232	232
EGR2	-0.61	0.64	-10000	0	-1.5	292	292
JAK2	-0.008	0.036	-10000	0	-0.83	1	1
JAK3	0.01	0.036	-10000	0	-0.29	14	14
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
JAK1	0.004	0.027	-10000	0	-0.8	1	1
COL1A2	-0.14	0.16	-10000	0	-1.7	2	2
CCL26	-0.46	0.46	-10000	0	-1.1	258	258
IL4R	-0.5	0.49	-10000	0	-1.2	240	240
PTPN6	0.022	0.018	-10000	0	-0.27	1	1
IL13RA2	-0.46	0.46	-10000	0	-1.1	226	226
IL13RA1	-0.007	0.026	-10000	0	-10000	0	0
IRF4	-0.22	0.48	-10000	0	-1.6	108	108
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.28	-10000	0	-0.69	162	162
GTF3A	0.013	0.016	-10000	0	-0.28	2	2
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL13RA1/JAK2	-0.014	0.042	-10000	0	-0.63	1	1
IRF4/BCL6	-0.2	0.43	-10000	0	-1.4	107	107
CD40LG	-0.032	0.18	-10000	0	-0.78	55	55
MAPK14	-0.26	0.28	-10000	0	-0.71	145	145
mitosis	-0.2	0.23	-10000	0	-0.63	79	79
STAT6	-0.53	0.54	-10000	0	-1.2	311	311
SPI1	0.007	0.024	-10000	0	-0.28	6	6
RPS6KB1	-0.19	0.22	-10000	0	-0.64	59	59
STAT6 (dimer)	-0.53	0.54	-10000	0	-1.2	311	311
STAT6 (dimer)/PARP14	-0.52	0.51	-10000	0	-1.1	346	346
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.23	-10000	0	-0.66	69	69
FRAP1	-0.21	0.24	-10000	0	-0.67	79	79
LTA	-0.47	0.46	-10000	0	-1.1	249	249
FES	-0.002	0.043	-10000	0	-0.8	3	3
T-helper 1 cell differentiation	0.52	0.52	1.2	311	-10000	0	311
CCL11	-0.49	0.44	-10000	0	-1.1	265	265
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.24	-10000	0	-0.66	70	70
IL2RG	-0.005	0.09	-10000	0	-0.36	52	52
IL10	-0.46	0.47	-10000	0	-1.1	232	232
IRS1	-0.033	0.16	-10000	0	-0.8	43	43
IRS2	-0.032	0.16	-10000	0	-0.8	41	41
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.46	-10000	0	-1.2	210	210
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.83	278	278
COL1A1	-0.18	0.17	-10000	0	-1.8	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.47	0.48	-10000	0	-1.2	194	194
IL2R gamma/JAK3	-0.013	0.072	-10000	0	-0.46	20	20
TFF3	-0.57	0.59	-10000	0	-1.3	310	310
ALOX15	-0.54	0.57	-10000	0	-1.3	273	273
MYBL1	-0.043	0.1	-10000	0	-0.29	154	154
T-helper 2 cell differentiation	-0.4	0.38	-10000	0	-0.87	292	292
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.008	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.24	-10000	0	-0.67	67	67
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.67	79	79
PI3K	-0.22	0.26	-10000	0	-0.72	79	79
DOK2	-0.003	0.047	-10000	0	-0.8	3	3
ETS1	0.019	0.056	-10000	0	-0.76	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.18	-10000	0	-0.68	15	15
ITGB3	-0.48	0.5	-10000	0	-1.2	233	233
PIGR	-1	0.75	-10000	0	-1.5	661	661
IGHE	0.046	0.04	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.67	15	15
BCL6	0.002	0.057	-10000	0	-0.8	5	5
OPRM1	-0.47	0.46	-10000	0	-1.1	249	249
RETNLB	-0.47	0.46	-10000	0	-1.2	219	219
SELP	-0.63	0.68	-10000	0	-1.6	312	312
AICDA	-0.45	0.44	-10000	0	-1.1	205	205

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.39	20	20
NFATC4	-0.088	0.16	-9999	-0.36	27	27
ERBB2IP	0.007	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-10000	0	0
mammary gland morphogenesis	-0.15	0.19	-9999	-0.39	380	380
JUN	-0.018	0.08	-9999	-0.37	6	6
HRAS	-0.003	0.027	-9999	-0.29	9	9
DOCK7	-0.12	0.19	-9999	-0.37	380	380
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.22	-9999	-0.47	380	380
AKT1	0.007	0.006	-9999	-10000	0	0
BAD	0.018	0.008	-9999	-10000	0	0
MAPK10	-0.11	0.14	-9999	-0.35	171	171
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.2	-9999	-0.43	380	380
RAF1	-0.08	0.16	-9999	-0.4	15	15
ErbB2/ErbB3/neuregulin 2	-0.26	0.25	-9999	-0.51	513	513
STAT3	0.001	0.004	-9999	-10000	0	0
cell migration	-0.062	0.13	-9999	-0.3	96	96
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.13	0.22	-9999	-0.51	162	162
FOS	-0.16	0.26	-9999	-0.54	309	309
NRAS	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	-0.15	0.19	-9999	-0.39	380	380
MAPK3	-0.1	0.18	-9999	-0.42	159	159
MAPK1	-0.1	0.18	-9999	-0.42	159	159
JAK2	-0.12	0.19	-9999	-0.37	381	381
NF2	-0.006	0.01	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.17	-9999	-0.36	380	380
NRG1	-0.29	0.39	-9999	-0.8	378	378
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.33	384	384
MAPK9	-0.069	0.088	-9999	-0.22	18	18
ERBB2	-0.016	0.055	-9999	-10000	0	0
ERBB3	0.001	0.044	-9999	-0.81	3	3
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.015	0.017	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.004	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.007	0.005	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.099	0.12	-9999	-0.32	23	23
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.042	-9999	-10000	0	0
CHRNA1	-0.09	0.16	-9999	-0.41	55	55
myelination	-0.082	0.16	-9999	-0.36	27	27
PPP3CB	-0.13	0.16	-9999	-0.36	167	167
KRAS	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.3	380	380
NRG2	-0.4	0.4	-9999	-0.8	510	510
mol:GDP	-0.12	0.18	-9999	-0.36	380	380
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.072	0.15	-9999	-0.4	13	13
SRC	0	0.009	-9999	-0.29	1	1
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.37	380	380
MAP2K1	-0.13	0.21	-9999	-0.48	158	158
heart morphogenesis	-0.15	0.19	-9999	-0.39	380	380
RAS family/GDP	-0.11	0.14	-9999	-0.39	17	17
GRB2	0	0.009	-9999	-0.29	1	1
PRKACA	-0.01	0.014	-9999	-10000	0	0
CHRNE	0.007	0.023	-9999	-0.18	6	6
HSP90AA1	0	0.009	-9999	-10000	0	0
activation of caspase activity	-0.007	0.006	-9999	-10000	0	0
nervous system development	-0.15	0.19	-9999	-0.39	380	380
CDC42	0	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.004	0.039	-10000	0	-0.29	19	19
EFNB1	0.017	0.053	-10000	0	-0.62	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.17	0.21	-10000	0	-0.42	415	415
Ephrin B2/EPHB1-2	-0.2	0.24	-10000	0	-0.49	414	414
neuron projection morphogenesis	-0.16	0.2	-10000	0	-0.4	415	415
Ephrin B1/EPHB1-2/Tiam1	-0.18	0.22	-10000	0	-0.45	415	415
DNM1	-0.006	0.067	-10000	0	-0.74	8	8
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.005	0.14	-10000	0	-0.74	33	33
YES1	-0.027	0.17	-10000	0	-0.99	32	32
Ephrin B1/EPHB1-2/NCK2	-0.18	0.22	-10000	0	-0.45	415	415
PI3K	-0.028	0.14	-10000	0	-0.71	41	41
mol:GDP	-0.18	0.22	-10000	0	-0.45	415	415
ITGA2B	-0.018	0.078	-10000	0	-0.8	3	3
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.027	0.17	-10000	0	-0.98	32	32
MAP3K7	-0.023	0.14	-10000	0	-0.8	32	32
FGR	-0.029	0.17	-10000	0	-0.99	32	32
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.047	0.17	-10000	0	-0.64	68	68
LYN	-0.027	0.17	-10000	0	-0.98	32	32
Ephrin B1/EPHB1-2/Src Family Kinases	-0.028	0.16	-10000	0	-0.93	32	32
Ephrin B1/EPHB1-2	-0.03	0.15	-10000	0	-0.87	32	32
SRC	-0.029	0.17	-10000	0	-0.99	32	32
ITGB3	-0.028	0.15	-10000	0	-0.75	39	39
EPHB1	-0.32	0.39	-10000	0	-0.8	415	415
EPHB4	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.63	38	38
BLK	-0.029	0.17	-10000	0	-0.99	32	32
HCK	-0.029	0.17	-10000	0	-0.99	32	32
regulation of stress fiber formation	0.18	0.22	0.45	415	-10000	0	415
MAPK8	0	0.14	-10000	0	-0.72	37	37
Ephrin B1/EPHB1-2/RGS3	-0.18	0.22	-10000	0	-0.45	415	415
endothelial cell migration	-0.017	0.12	-10000	0	-0.7	32	32
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.019	0.16	-10000	0	-0.92	32	32
regulation of focal adhesion formation	0.18	0.22	0.45	415	-10000	0	415
chemotaxis	0.18	0.22	0.45	415	-10000	0	415
PIK3CA	0	0.009	-10000	0	-0.29	1	1
Rac1/GTP	-0.17	0.2	-10000	0	-0.41	415	415
angiogenesis	-0.03	0.15	-10000	0	-0.86	32	32
LCK	-0.031	0.17	-10000	0	-0.99	32	32

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.057	0.16	-10000	0	-0.54	104	104
cell-cell adhesion	0.17	0.22	0.68	73	-10000	0	73
Ephrin B/EPHB2/RasGAP	-0.04	0.12	-10000	0	-0.45	87	87
ITSN1	-0.001	0.025	-10000	0	-0.8	1	1
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.017	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.22	0.26	-10000	0	-0.54	414	414
HRAS/GDP	-0.18	0.23	-10000	0	-0.66	94	94
Ephrin B/EPHB1/GRB7	-0.22	0.28	-10000	0	-0.53	434	434
Endophilin/SYNJ1	-0.037	0.12	-10000	0	-0.42	87	87
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
Ephrin B/EPHB1/Src	-0.22	0.28	-10000	0	-0.52	433	433
endothelial cell migration	-0.005	0.044	-10000	0	-0.45	10	10
GRB2	0	0.009	-10000	0	-0.29	1	1
GRB7	-0.021	0.077	-10000	0	-0.3	72	72
PAK1	-0.046	0.14	-10000	0	-0.46	96	96
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
RRAS	-0.038	0.12	-10000	0	-0.43	87	87
DNM1	-0.006	0.066	-10000	0	-0.74	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.21	0.26	-10000	0	-0.49	433	433
lamellipodium assembly	-0.17	0.22	-10000	0	-0.68	73	73
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.15	0.19	-10000	0	-0.37	414	414
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
EPHB2	-0.005	0.039	-10000	0	-0.29	19	19
EPHB3	-0.004	0.033	-10000	0	-0.29	14	14
EPHB1	-0.32	0.39	-10000	0	-0.8	415	415
EPHB4	0	0.009	-10000	0	-0.29	1	1
mol:GDP	-0.16	0.21	-10000	0	-0.64	92	92
Ephrin B/EPHB2	-0.04	0.13	-10000	0	-0.46	87	87
Ephrin B/EPHB3	-0.04	0.13	-10000	0	-0.46	87	87
JNK cascade	-0.18	0.22	-10000	0	-0.44	414	414
Ephrin B/EPHB1	-0.22	0.28	-10000	0	-0.53	433	433
RAP1/GDP	-0.13	0.18	-10000	0	-0.56	86	86
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.067	0.22	-10000	0	-0.8	87	87
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.24	-10000	0	-0.49	414	414
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.18	0.23	-10000	0	-0.69	91	91
Rap1/GTP	-0.17	0.22	-10000	0	-0.71	72	72
axon guidance	-0.057	0.16	-10000	0	-0.54	104	104
MAPK3	-0.1	0.19	-10000	0	-0.53	68	68
MAPK1	-0.1	0.19	-10000	0	-0.53	68	68
Rac1/GDP	-0.14	0.19	-10000	0	-0.59	87	87
actin cytoskeleton reorganization	-0.13	0.17	-10000	0	-0.52	77	77
CDC42/GDP	-0.14	0.19	-10000	0	-0.59	87	87
PI3K	-0.005	0.045	-10000	0	-0.46	10	10
EFNA5	-0.081	0.24	-10000	0	-0.8	105	105
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.028	0.094	-10000	0	-0.33	87	87
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.17	0.22	-10000	0	-0.67	76	76
PTK2	0.042	0.051	-10000	0	-10000	0	0
MAP4K4	-0.18	0.22	-10000	0	-0.45	414	414
SRC	0	0.009	-10000	0	-0.29	1	1
KALRN	-0.014	0.1	-10000	0	-0.8	18	18
Intersectin/N-WASP	-0.001	0.019	-10000	0	-0.61	1	1
neuron projection morphogenesis	-0.14	0.18	-10000	0	-0.55	76	76
MAP2K1	-0.14	0.18	-10000	0	-0.56	69	69
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.19	0.24	-10000	0	-0.48	414	414
cell migration	-0.12	0.22	-10000	0	-0.64	69	69
NRAS	-0.001	0.013	-10000	0	-10000	0	0
SYNJ1	-0.038	0.12	-10000	0	-0.43	87	87
PXN	0	0	-10000	0	-10000	0	0
TF	-0.25	0.27	-10000	0	-0.46	596	596
HRAS/GTP	-0.19	0.24	-10000	0	-0.45	433	433
Ephrin B1/EPHB1-2	-0.2	0.24	-10000	0	-0.49	414	414
cell adhesion mediated by integrin	0.007	0.13	0.42	87	-10000	0	87
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.2	0.26	-10000	0	-0.48	433	433
RAC1-CDC42/GTP	-0.17	0.22	-10000	0	-0.69	73	73
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.13	0.18	-10000	0	-0.56	86	86
ruffle organization	-0.18	0.22	-10000	0	-0.71	73	73
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.003	0.14	-10000	0	-0.43	89	89
Ephrin B/EPHB2/KALRN	-0.047	0.15	-10000	0	-0.49	96	96
ROCK1	0.022	0.024	-10000	0	-0.49	1	1
RAS family/GDP	-0.12	0.16	-10000	0	-0.53	69	69
Rac1/GTP	-0.18	0.24	-10000	0	-0.75	73	73
Ephrin B/EPHB1/Src/Paxillin	-0.16	0.2	-10000	0	-0.38	433	433

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.009	-9999	-0.29	1	1
CCL5	-0.015	0.081	-9999	-0.36	44	44
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.078	0.11	-9999	-0.32	150	150
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.072	0.097	-9999	-0.35	44	44
Syndecan-1/Syntenin	-0.072	0.097	-9999	-0.32	103	103
MAPK3	-0.046	0.096	-9999	-0.48	5	5
HGF/MET	-0.14	0.28	-9999	-0.66	220	220
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.29	1	1
BSG	0	0.009	-9999	-0.29	1	1
keratinocyte migration	-0.071	0.096	-9999	-0.32	102	102
Syndecan-1/RANTES	-0.08	0.11	-9999	-0.34	106	106
Syndecan-1/CD147	-0.063	0.094	-9999	-0.46	7	7
Syndecan-1/Syntenin/PIP2	-0.069	0.094	-9999	-0.31	103	103
LAMA5	0	0.009	-9999	-0.29	1	1
positive regulation of cell-cell adhesion	-0.068	0.092	-9999	-0.3	103	103
MMP7	-0.12	0.28	-9999	-0.72	178	178
HGF	-0.053	0.2	-9999	-0.8	68	68
Syndecan-1/CASK	-0.074	0.1	-9999	-0.3	150	150
Syndecan-1/HGF/MET	-0.17	0.25	-9999	-0.6	223	223
regulation of cell adhesion	-0.039	0.093	-9999	-0.46	5	5
HPSE	-0.007	0.052	-9999	-0.34	20	20
positive regulation of cell migration	-0.078	0.11	-9999	-0.32	150	150
SDC1	-0.078	0.11	-9999	-0.32	150	150
Syndecan-1/Collagen	-0.078	0.11	-9999	-0.32	150	150
PPIB	-0.001	0.016	-9999	-0.29	3	3
MET	-0.13	0.3	-9999	-0.8	172	172
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.29	453	453
MAPK1	-0.046	0.096	-9999	-0.48	5	5
homophilic cell adhesion	-0.077	0.11	-9999	-0.32	150	150
MMP1	-0.22	0.12	-9999	-0.29	787	787

×

IGF1 pathway

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
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.1	0.24	-10000	0	-0.5	240	240
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
IRS1/Crk	-0.12	0.23	-10000	0	-0.5	254	254
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.24	-10000	0	-0.54	240	240
AKT1	-0.069	0.22	-10000	0	-0.74	47	47
BAD	-0.056	0.2	-10000	0	-0.68	47	47
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.24	-10000	0	-0.49	254	254
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.23	-10000	0	-0.5	254	254
RAF1	-0.048	0.19	-10000	0	-0.64	45	45
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.11	0.22	-10000	0	-0.48	240	240
YWHAZ	-0.001	0.016	-10000	0	-0.29	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.25	-10000	0	-0.54	254	254
PIK3CA	0	0.009	-10000	0	-0.29	1	1
RPS6KB1	-0.069	0.22	-10000	0	-0.74	47	47
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.041	0.16	-10000	0	-0.52	45	45
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.2	-10000	0	-0.73	44	44
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.19	-10000	0	-0.43	240	240
IGF-1R heterotetramer	-0.034	0.14	-10000	0	-0.85	24	24
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.23	-10000	0	-0.5	254	254
Crk/p130 Cas/Paxillin	-0.11	0.21	-10000	0	-0.45	240	240
IGF1R	-0.034	0.14	-10000	0	-0.85	24	24
IGF1	-0.18	0.35	-10000	0	-0.83	231	231
IRS2/Crk	-0.13	0.25	-10000	0	-0.52	256	256
PI3K	-0.12	0.23	-10000	0	-0.49	241	241
apoptosis	0.081	0.15	0.56	46	-10000	0	46
HRAS/GDP	-0.002	0.018	-10000	0	-10000	0	0
PRKCD	-0.095	0.25	-10000	0	-0.54	240	240
RAF1/14-3-3 E	-0.076	0.14	-10000	0	-0.53	45	45
BAD/14-3-3	-0.086	0.16	-10000	0	-0.61	46	46
PRKCZ	-0.069	0.22	-10000	0	-0.74	48	48
Crk/p130 Cas/Paxillin/FAK1	-0.085	0.16	-10000	0	-0.63	45	45
PTPN1	-0.003	0.03	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.14	0.25	-10000	0	-0.57	240	240
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.21	-10000	0	-0.47	240	240
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.23	-10000	0	-0.49	254	254
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.24	-10000	0	-0.49	254	254
IRS1	-0.13	0.25	-10000	0	-0.54	254	254
IRS2	-0.12	0.28	-10000	0	-0.54	267	267
IGF-1R heterotetramer/IGF1	-0.16	0.29	-10000	0	-0.67	240	240
GRB2	0	0.009	-10000	0	-0.29	1	1
PDPK1	-0.11	0.21	-10000	0	-0.8	48	48
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.58	246	246
SHC1	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.036	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.082	0.16	-9999	-0.39	196	196
JUN	-0.051	0.14	-9999	-0.42	61	61
HRAS	-0.003	0.027	-9999	-0.29	9	9
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.2	-9999	-0.53	198	198
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.2	-9999	-0.53	198	198
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.19	-9999	-0.5	189	189
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.48	198	198
GRB7	-0.021	0.077	-9999	-0.3	72	72
RET51/GFRalpha1/GDNF	-0.15	0.2	-9999	-0.53	198	198
MAPKKK cascade	-0.1	0.17	-9999	-0.43	195	195
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.24	-9999	-0.57	201	201
lamellipodium assembly	-0.083	0.15	-9999	-0.37	196	196
RET51/GFRalpha1/GDNF/SHC	-0.15	0.2	-9999	-0.53	198	198
PIK3CA	0	0.009	-9999	-0.29	1	1
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.5	189	189
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.5	189	189
MAPK3	-0.12	0.17	-9999	-0.45	195	195
DOK1	-0.001	0.018	-9999	-0.29	4	4
DOK6	-0.013	0.095	-9999	-0.8	14	14
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.54	54	54
DOK5	-0.02	0.12	-9999	-0.72	29	29
GFRA1	-0.16	0.31	-9999	-0.69	245	245
MAPK8	-0.077	0.14	-9999	-0.34	200	200
HRAS/GTP	-0.12	0.19	-9999	-0.49	195	195
tube development	-0.096	0.18	-9999	-0.47	189	189
MAPK1	-0.12	0.17	-9999	-0.45	195	195
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.066	0.13	-9999	-0.34	189	189
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.15	0.2	-9999	-0.52	204	204
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.2	-9999	-0.53	198	198
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.56	213	213
PRKCA	-0.021	0.13	-9999	-0.77	29	29
HRAS/GDP	-0.002	0.018	-9999	-10000	0	0
CREB1	-0.073	0.15	-9999	-0.38	189	189
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.065	0.13	-9999	-0.34	189	189
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.55	200	200
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.16	-9999	-0.31	386	386
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.05	0.14	-9999	-0.41	61	61
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.5	189	189
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.066	0.13	-9999	-0.34	189	189
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.083	0.14	-9999	-0.36	195	195
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.083	0.14	-9999	-0.36	195	195
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.084	0.15	-9999	-0.37	195	195
PI3K	-0.13	0.24	-9999	-0.59	202	202
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.096	0.18	-9999	-0.47	189	189
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.078	0.13	-9999	-0.41	46	46
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.2	-9999	-0.53	198	198
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.8	43	43
IRS2	-0.032	0.16	-9999	-0.8	41	41
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.15	-9999	-0.37	195	195
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.55	223	223
GRB2	0	0.009	-9999	-0.29	1	1
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.016	0.065	-9999	-0.29	56	56
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.6	209	209
Rac1/GTP	-0.1	0.18	-9999	-0.45	196	196
RET9/GFRalpha1/GDNF	-0.12	0.21	-9999	-0.54	193	193
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.62	193	193

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.027	0.063	-10000	0	-0.5	2	2
epithelial cell differentiation	-0.021	0.062	-10000	0	-0.48	7	7
ITCH	0.009	0.021	-10000	0	-10000	0	0
WWP1	0.007	0.068	-10000	0	-10000	0	0
FYN	-0.002	0.035	-10000	0	-0.8	2	2
EGFR	-0.29	0.39	-10000	0	-0.8	383	383
PRL	-0.004	0.032	-10000	0	-0.29	13	13
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.47	70	70
PTPRZ1	-0.42	0.4	-10000	0	-0.8	551	551
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.2	-10000	0	-0.42	378	378
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.2	0.24	-10000	0	-0.5	378	378
ADAM17	0.009	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.086	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.057	0.13	-10000	0	-0.54	57	57
NCOR1	-0.001	0.025	-10000	0	-0.8	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.22	-10000	0	-0.47	378	378
GRIN2B	-0.18	0.26	-10000	0	-0.47	427	427
ErbB4/ErbB2/betacellulin	-0.05	0.11	-10000	0	-0.47	58	58
STAT1	-0.005	0.039	-10000	0	-0.29	19	19
HBEGF	-0.002	0.035	-10000	0	-0.8	2	2
PRLR	-0.007	0.065	-10000	0	-0.53	13	13
E4ICDs/ETO2	-0.036	0.093	-10000	0	-0.56	19	19
axon guidance	0.044	0.12	-10000	0	-0.42	2	2
NEDD4	0.009	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.007	0.053	-10000	0	-0.62	6	6
CBFA2T3	-0.016	0.11	-10000	0	-0.7	24	24
ErbB4/ErbB2/HBEGF	-0.025	0.051	-10000	0	-0.45	2	2
MAPK3	-0.15	0.19	-10000	0	-0.49	70	70
STAT1 (dimer)	-0.028	0.063	-10000	0	-10000	0	0
MAPK1	-0.15	0.19	-10000	0	-0.49	70	70
JAK2	-0.001	0.025	-10000	0	-0.8	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.22	-10000	0	-0.48	378	378
NRG1	-0.21	0.31	-10000	0	-0.62	378	378
NRG3	-0.051	0.19	-10000	0	-0.65	82	82
NRG2	-0.4	0.4	-10000	0	-0.8	510	510
NRG4	-0.005	0.039	-10000	0	-0.29	19	19
heart development	0.044	0.12	-10000	0	-0.42	2	2
neural crest cell migration	-0.19	0.22	-10000	0	-0.47	378	378
ERBB2	0.01	0.058	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.026	0.059	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.19	0.22	-10000	0	-0.47	378	378
apoptosis	0.057	0.14	0.53	57	-10000	0	57
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.27	0.24	-10000	0	-0.51	510	510
ErbB4/ErbB2/epiregulin	-0.085	0.15	-10000	0	-0.46	124	124
ErbB4/ErbB4/betacellulin/betacellulin	-0.054	0.13	-10000	0	-0.51	58	58
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.022	0.065	-10000	0	-0.52	9	9
MDM2	0.008	0.075	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.23	-10000	0	-0.48	378	378
STAT5A	0.044	0.12	-10000	0	-0.47	7	7
ErbB4/EGFR/neuregulin 1 beta	-0.35	0.36	-10000	0	-0.66	526	526
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.056	-10000	0	-0.47	1	1
STAT5A (dimer)	-0.022	0.067	-10000	0	-0.52	7	7
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.026	0.12	-10000	0	-0.44	4	4
LRIG1	-0.002	0.035	-10000	0	-0.8	2	2
EREG	-0.12	0.26	-10000	0	-0.61	200	200
BTC	-0.045	0.18	-10000	0	-0.79	60	60
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.044	0.12	-10000	0	-0.42	2	2
ERBB4	-0.032	0.073	-10000	0	-10000	0	0
STAT5B	-0.002	0.043	-10000	0	-0.8	3	3
YAP1	-0.01	0.044	-10000	0	-0.64	4	4
GRB2	0	0.009	-10000	0	-0.29	1	1
ErbB4/ErbB2/neuregulin 4	-0.026	0.052	-10000	0	-10000	0	0
glial cell differentiation	0.024	0.055	0.46	1	-10000	0	1
WWOX	-0.001	0.013	-10000	0	-10000	0	0
cell proliferation	-0.12	0.24	-10000	0	-0.47	200	200

×

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	-0.12	0.2	-9999	-0.6	132	132
SMAD6-7/SMURF1	-0.001	0.016	-9999	-0.53	1	1
NOG	-0.026	0.13	-9999	-0.6	45	45
SMAD9	-0.11	0.26	-9999	-0.78	116	116
SMAD4	-0.001	0.025	-9999	-0.8	1	1
SMAD5	-0.076	0.18	-9999	-0.5	118	118
BMP7/USAG1	-0.35	0.35	-9999	-0.67	535	535
SMAD5/SKI	-0.088	0.16	-9999	-0.52	87	87
SMAD1	0.026	0.03	-9999	-10000	0	0
BMP2	-0.14	0.31	-9999	-0.8	185	185
SMAD1/SMAD1/SMAD4	-0.002	0.015	-9999	-10000	0	0
BMPR1A	-0.002	0.035	-9999	-0.8	2	2
BMPR1B	-0.14	0.18	-9999	-0.32	445	445
BMPR1A-1B/BAMBI	-0.092	0.14	-9999	-0.6	57	57
AHSG	-0.004	0.033	-9999	-0.29	14	14
CER1	-0.001	0.016	-9999	-0.29	3	3
BMP2-4/CER1	-0.13	0.25	-9999	-0.58	232	232
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.2	-9999	-0.61	100	100
BMP2-4 (homodimer)	-0.15	0.28	-9999	-0.66	232	232
RGMB	-0.001	0.025	-9999	-0.8	1	1
BMP6/BMPR2/BMPR1A-1B	-0.097	0.16	-9999	-0.55	103	103
RGMA	-0.11	0.27	-9999	-0.8	138	138
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.62	103	103
BMP2-4/USAG1	-0.38	0.37	-9999	-0.66	592	592
SMAD6/SMURF1/SMAD5	-0.088	0.16	-9999	-0.52	87	87
SOSTDC1	-0.39	0.4	-9999	-0.8	507	507
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.57	107	107
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.061	0.21	-9999	-0.8	78	78
HFE2	-0.003	0.027	-9999	-0.29	9	9
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-0.29	1	1
BMP2-4/CHRD	-0.14	0.27	-9999	-0.62	236	236
SMAD5/SMAD5/SMAD4	-0.088	0.16	-9999	-0.52	88	88
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.087	0.17	-9999	-0.53	101	101
BMP7 (homodimer)	-0.077	0.23	-9999	-0.65	123	123
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.05	0.16	-9999	-0.62	78	78
SMAD1/SKI	0.004	0.019	-9999	-10000	0	0
SMAD6	-0.001	0.025	-9999	-0.8	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.13	0.25	-9999	-0.58	232	232
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.038	0.12	-9999	-0.36	109	109
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.01	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.09	0.12	-9999	-0.62	27	27
CHRDL1	-0.55	0.37	-9999	-0.8	712	712
ENDOFIN/SMAD1	0.004	0.019	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.014	-9999	-0.37	1	1
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.034	0.14	-9999	-0.51	70	70
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.48	0.37	-9999	-0.68	729	729
BMP2-4/GREM1	-0.15	0.26	-9999	-0.59	237	237
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.1	0.24	-9999	-0.73	116	116
SMAD1/SMAD6	0.004	0.019	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.077	0.23	-9999	-0.65	123	123
BMP6	-0.061	0.21	-9999	-0.8	78	78
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.1	0.19	-9999	-0.6	100	100
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	0.004	0.019	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.001	0.02	-9999	-0.29	5	5
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.59	163	163
CHRD	-0.032	0.13	-9999	-0.43	78	78
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.24	-9999	-0.54	190	190
BMP4	-0.053	0.2	-9999	-0.8	69	69
FST	-0.036	0.16	-9999	-0.76	49	49
BMP2-4/NOG	-0.14	0.26	-9999	-0.6	247	247
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.095	0.16	-9999	-0.54	107	107

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.01	0.039	-9999	-0.55	3	3
NFATC2	-0.04	0.16	-9999	-0.56	93	93
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.21	0.37	-9999	-0.72	287	287
PTGS2	-0.32	0.47	-9999	-0.86	403	403
JUNB	-0.001	0.013	-9999	-0.29	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.009	-9999	-10000	0	0
CALM1	0	0.003	-9999	-10000	0	0
JUN	-0.005	0.067	-9999	-0.81	7	7
mol:Ca2+	-0.007	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
FOSL1	-0.011	0.073	-9999	-0.8	6	6
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.075	0.15	-9999	-0.54	71	71
FOS	-0.24	0.37	-9999	-0.82	307	307
IFNG	-0.22	0.35	-9999	-0.69	286	286
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.85	283	283
FASLG	-0.2	0.35	-9999	-0.69	284	284
NFAT1-c-4/ICER1	-0.058	0.14	-9999	-0.48	93	93
IL2RA	-0.21	0.35	-9999	-0.69	286	286
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.2	0.34	-9999	-0.68	283	283
JunB/Fra1/NFAT1-c-4	-0.057	0.14	-9999	-0.5	72	72
IL4	-0.2	0.34	-9999	-0.68	280	280
IL2	-0.01	0.025	-9999	-10000	0	0
IL3	-0.024	0.026	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-0.29	1	1
BATF3	-0.002	0.029	-9999	-0.42	4	4
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-0.29	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.072	0.23	-9999	-0.8	93	93
GNB1/GNG2	-0.14	0.23	-9999	-0.64	120	120
mol:DAG	-0.13	0.2	-9999	-0.6	105	105
PLCG1	-0.13	0.21	-9999	-0.63	105	105
YES1	-0.15	0.23	-9999	-0.62	127	127
FZD3	-0.009	0.082	-9999	-0.8	11	11
FZD6	-0.007	0.075	-9999	-0.8	9	9
G protein	-0.13	0.21	-9999	-0.63	107	107
MAP3K7	-0.068	0.18	-9999	-0.49	103	103
mol:Ca2+	-0.092	0.21	-9999	-0.58	105	105
mol:IP3	-0.13	0.2	-9999	-0.6	105	105
NLK	-0.005	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.082	0.2	-9999	-0.53	110	110
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	366	366
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.15	0.23	-9999	-0.66	112	112
GO:0007205	-0.093	0.22	-9999	-0.59	105	105
WNT6	-0.17	0.32	-9999	-0.71	247	247
WNT4	-0.022	0.12	-9999	-0.53	42	42
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.56	184	184
GNG2	-0.009	0.086	-9999	-0.8	12	12
WNT5A	-0.014	0.1	-9999	-0.6	25	25
WNT11	-0.17	0.32	-9999	-0.77	227	227
CDC42	-0.11	0.23	-9999	-0.62	111	111

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.1	0.23	-10000	0	-0.61	172	172
CRKL	-0.039	0.16	-10000	0	-0.35	172	172
mol:PIP3	-0.018	0.036	0.79	2	-10000	0	2
AKT1	0.003	0.022	0.49	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.029	0.15	-10000	0	-0.33	172	172
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
HGF/MET/SHIP2	-0.12	0.24	-10000	0	-0.57	220	220
MAP3K5	-0.02	0.15	-10000	0	-0.54	24	24
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.11	0.22	-10000	0	-0.52	220	220
AP1	-0.19	0.27	-10000	0	-0.59	308	308
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.23	0.36	-10000	0	-0.78	308	308
STAT3 (dimer)	-0.038	0.16	-10000	0	-0.34	220	220
GAB1/CRKL/SHP2/PI3K	-0.063	0.13	-10000	0	-0.54	26	26
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.065	0.13	-10000	0	-0.33	172	172
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.035	-10000	0	-0.8	2	2
ELK1	-0.043	0.1	-10000	0	-0.27	172	172
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.045	0.092	-10000	0	-0.42	20	20
PAK1	0.008	0.029	0.45	2	-10000	0	2
HGF/MET/RANBP10	-0.12	0.24	-10000	0	-0.57	220	220
HRAS	-0.15	0.3	-10000	0	-0.78	172	172
DOCK1	-0.029	0.15	-10000	0	-0.55	20	20
GAB1	-0.049	0.16	-10000	0	-0.35	220	220
CRK	-0.039	0.16	-10000	0	-0.33	220	220
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.3	-10000	0	-0.71	220	220
JUN	-0.005	0.066	-10000	0	-0.8	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.076	0.15	-10000	0	-0.36	220	220
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
cell morphogenesis	-0.017	0.17	-10000	0	-0.6	26	26
GRB2/SHC	-0.065	0.13	-10000	0	-0.33	172	172
FOS	-0.24	0.37	-10000	0	-0.8	307	307
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.043	0.1	-10000	0	-0.27	172	172
HGF/MET/MUC20	-0.12	0.25	-10000	0	-0.58	220	220
cell migration	-0.064	0.13	-10000	0	-0.33	172	172
GRB2	0	0.009	-10000	0	-0.29	1	1
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.1	0.23	-10000	0	-0.61	172	172
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.075	0.15	-10000	0	-0.36	220	220
MET/MUC20	-0.1	0.23	-10000	0	-0.62	172	172
RAP1B	-0.019	0.14	-10000	0	-0.5	20	20
RAP1A	-0.019	0.14	-10000	0	-0.5	20	20
HGF/MET/RANBP9	-0.12	0.24	-10000	0	-0.57	220	220
RAF1	-0.1	0.29	-10000	0	-0.72	172	172
STAT3	-0.072	0.14	-10000	0	-0.34	220	220
cell proliferation	-0.059	0.23	-10000	0	-0.48	220	220
RPS6KB1	-0.026	0.052	-10000	0	-10000	0	0
MAPK3	-0.043	0.092	-10000	0	-0.25	172	172
MAPK1	-0.043	0.092	-10000	0	-0.25	172	172
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.14	-10000	0	-0.48	31	31
SRC	-0.07	0.14	-10000	0	-0.62	20	20
PI3K	-0.07	0.14	-10000	0	-0.35	180	180
MET/Glomulin	-0.093	0.21	-10000	0	-0.56	172	172
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.083	0.27	-10000	0	-0.65	172	172
MET	-0.13	0.3	-10000	0	-0.8	172	172
MAP4K1	-0.028	0.15	-10000	0	-0.33	173	173
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.083	0.27	-10000	0	-0.65	172	172
BAD	0.011	0.021	0.45	2	-10000	0	2
MAP2K4	-0.01	0.14	-10000	0	-0.48	25	25
SHP2/GRB2/SOS1/GAB1	-0.094	0.19	-10000	0	-0.51	172	172
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.07	0.14	-10000	0	-0.36	172	172
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.053	0.2	-10000	0	-0.8	68	68
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.066	0.13	-10000	0	-0.33	172	172
PDPK1	-0.006	0.026	0.57	2	-10000	0	2
HGF/MET/SHIP	-0.12	0.24	-10000	0	-0.57	220	220

×

Nongenotropic Androgen 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
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.068	0.17	-10000	0	-0.49	142	142
regulation of S phase of mitotic cell cycle	-0.041	0.12	-10000	0	-0.35	134	134
GNAO1	-0.031	0.13	-10000	0	-0.48	66	66
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.001	-10000	0	-10000	0	0
MAP2K1	-0.042	0.16	-10000	0	-0.43	131	131
T-DHT/AR	-0.079	0.21	-10000	0	-0.63	131	131
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	307	307
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	50	50
mol:GDP	-0.08	0.21	-10000	0	-0.62	133	133
cell proliferation	-0.1	0.24	-10000	0	-0.54	112	112
PIK3CA	0	0.009	-10000	0	-0.29	1	1
FOS	-0.23	0.42	-10000	0	-0.87	307	307
mol:Ca2+	-0.016	0.027	-10000	0	-0.077	132	132
MAPK3	-0.073	0.2	-10000	0	-0.61	61	61
MAPK1	-0.045	0.12	-10000	0	-0.3	59	59
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.001	0.002	-10000	0	-0.005	307	307
cAMP biosynthetic process	0.012	0.024	-10000	0	-10000	0	0
GNG2	-0.009	0.086	-10000	0	-0.8	12	12
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	307	307
HRAS/GTP	-0.066	0.15	-10000	0	-0.46	131	131
actin cytoskeleton reorganization	-0.004	0.042	-10000	0	-0.43	10	10
SRC	0	0.009	-10000	0	-0.29	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	307	307
PI3K	-0.005	0.053	-10000	0	-0.54	10	10
apoptosis	0.1	0.23	0.43	307	-10000	0	307
T-DHT/AR/PELP1	-0.069	0.18	-10000	0	-0.54	131	131
HRAS/GDP	-0.077	0.2	-10000	0	-0.6	132	132
CREB1	-0.11	0.24	-10000	0	-0.46	307	307
RAC1-CDC42/GTP	-0.004	0.043	-10000	0	-0.44	10	10
AR	-0.1	0.27	-10000	0	-0.8	132	132
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.043	0.16	-10000	0	-0.45	131	131
RAC1-CDC42/GDP	-0.072	0.19	-10000	0	-0.56	131	131
T-DHT/AR/PELP1/Src	-0.063	0.17	-10000	0	-0.5	131	131
MAP2K2	-0.042	0.16	-10000	0	-0.43	131	131
T-DHT/AR/PELP1/Src/PI3K	-0.042	0.12	-10000	0	-0.35	134	134
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.037	0.11	-10000	0	-0.49	36	36
mol:T-DHT	-0.001	0.001	0.001	57	-0.003	249	306
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.005	0.059	-10000	0	-0.62	9	9
Gi family/GTP	-0.048	0.1	-10000	0	-0.3	84	84
CDC42	0	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.1	0.12	-10000	0	-0.34	77	77
NT3 (dimer)/TRKC	-0.3	0.37	-10000	0	-0.7	441	441
NT3 (dimer)/TRKB	-0.51	0.45	-10000	0	-0.8	666	666
SHC/Grb2/SOS1/GAB1/PI3K	-0.003	0.032	-10000	0	-0.32	10	10
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.07	0.22	-10000	0	-0.8	81	81
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DYNLT1	0	0.009	-10000	0	-10000	0	0
NTRK1	-0.01	0.066	-10000	0	-0.36	29	29
NTRK2	-0.42	0.4	-10000	0	-0.8	549	549
NTRK3	-0.28	0.38	-10000	0	-0.8	361	361
NT-4/5 (dimer)/TRKB	-0.6	0.49	-10000	0	-0.87	716	716
neuron apoptosis	0.24	0.24	0.59	291	-10000	0	291
SHC 2-3/Grb2	-0.27	0.28	-10000	0	-0.66	291	291
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.25	0.29	-10000	0	-0.68	275	275
SHC3	-0.25	0.28	-10000	0	-0.66	280	280
STAT3 (dimer)	-0.005	0.03	-10000	0	-0.38	4	4
NT3 (dimer)/TRKA	-0.25	0.32	-10000	0	-0.62	421	421
RIN/GDP	-0.067	0.12	-10000	0	-0.28	63	63
GIPC1	-0.001	0.016	-10000	0	-0.29	3	3
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
DNAJA3	-0.14	0.21	-10000	0	-0.43	332	332
RIN/GTP	0	0.009	-10000	0	-10000	0	0
CCND1	0.018	0.076	-10000	0	-1	4	4
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.28	0.38	-10000	0	-0.8	363	363
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
NGF (dimer)/TRKA/MATK	-0.027	0.11	-10000	0	-0.56	35	35
TRKA/NEDD4-2	-0.007	0.051	-10000	0	-0.61	5	5
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.014	0.099	-10000	0	-0.64	22	22
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.004	0.044	-10000	0	-0.38	11	11
RIT2	-0.001	0.013	-10000	0	-0.29	2	2
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.028	-10000	0	-10000	0	0
DNM1	-0.006	0.066	-10000	0	-0.74	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.14	0.2	-10000	0	-0.42	332	332
mol:GDP	-0.1	0.18	-10000	0	-0.37	226	226
NGF (dimer)	-0.014	0.098	-10000	0	-0.64	22	22
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.063	0.12	-10000	0	-0.28	64	64
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
BDNF (dimer)/TRKB	-0.32	0.3	-10000	0	-0.58	575	575
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0.004	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.29	-10000	0	-0.76	176	176
RAP1/GDP	-0.074	0.085	-10000	0	-0.25	38	38
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.07	0.22	-10000	0	-0.8	81	81
ubiquitin-dependent protein catabolic process	-0.015	0.076	-10000	0	-0.53	20	20
Schwann cell development	-0.06	0.044	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.012	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.001	0.011	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.44	0.39	-10000	0	-0.67	679	679
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.11	0.099	-10000	0	-10000	0	0
STAT3	-0.005	0.03	-10000	0	-0.38	4	4
axon guidance	-0.41	0.35	-10000	0	-0.62	679	679
MAPK3	0.006	0.1	-10000	0	-0.51	35	35
MAPK1	0.006	0.1	-10000	0	-0.51	35	35
CDC42/GDP	-0.063	0.12	-10000	0	-0.28	65	65
NTF3	-0.13	0.29	-10000	0	-0.76	176	176
NTF4	-0.28	0.38	-10000	0	-0.8	363	363
NGF (dimer)/TRKA/FAIM	-0.014	0.075	-10000	0	-0.53	19	19
PI3K	-0.006	0.06	-10000	0	-0.61	10	10
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.16	0.22	-10000	0	-0.45	335	335
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.25	0.34	-10000	0	-0.61	443	443
RGS19	-0.001	0.013	-10000	0	-0.29	2	2
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.083	-10000	0	-10000	0	0
Rac1/GDP	-0.063	0.12	-10000	0	-0.28	64	64
NGF (dimer)/TRKA/GRIT	-0.015	0.076	-10000	0	-0.54	19	19
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.63	23	23
NGF (dimer)/TRKA/NEDD4-2	-0.015	0.076	-10000	0	-0.53	20	20
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.25	0.37	-10000	0	-0.8	325	325
NGF (dimer)/TRKA/GIPC/GAIP	-0.009	0.053	-10000	0	-0.34	25	25
RAS family/GTP/PI3K	-0.004	0.033	-10000	0	-0.34	10	10
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.01	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
MAPKKK cascade	-0.065	0.12	-10000	0	-0.82	19	19
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.047	-10000	0	-0.61	4	4
SQSTM1	0	0.009	-10000	0	-0.29	1	1
BDNF (dimer)/TRKB/GIPC	-0.3	0.28	-10000	0	-0.53	575	575
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.012	0.064	-10000	0	-0.45	20	20
MATK	-0.021	0.11	-10000	0	-0.8	18	18
NEDD4L	-0.001	0.025	-10000	0	-0.8	1	1
RAS family/GDP	-0.067	0.08	-10000	0	-0.24	3	3
NGF (dimer)/TRKA	-0.15	0.22	-10000	0	-0.46	337	337
Rac1/GTP	-0.13	0.14	-10000	0	-0.34	251	251
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.17	0.39	-9999	-1.1	73	73
IL23A	-0.18	0.4	-9999	-1.1	77	77
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.32	-9999	-0.89	132	132
positive regulation of T cell mediated cytotoxicity	-0.19	0.42	-9999	-0.86	226	226
ITGA3	-0.17	0.39	-9999	-0.95	108	108
IL17F	-0.11	0.28	-9999	-0.65	90	90
IL12B	-0.049	0.12	-9999	-0.29	155	155
STAT1 (dimer)	-0.22	0.38	-9999	-0.85	199	199
CD4	-0.16	0.38	-9999	-0.94	96	96
IL23	-0.18	0.38	-9999	-1	77	77
IL23R	-0.013	0.087	-9999	-10000	0	0
IL1B	-0.18	0.41	-9999	-1	120	120
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.17	0.38	-9999	-0.93	108	108
TYK2	0.011	0.017	-9999	-10000	0	0
STAT4	-0.032	0.16	-9999	-0.79	42	42
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.026	0.15	-9999	-0.74	42	42
IL12RB1	-0.002	0.071	-9999	-0.32	42	42
PIK3CA	0	0.009	-9999	-0.29	1	1
IL12Rbeta1/TYK2	-0.003	0.052	-9999	-0.62	2	2
IL23R/JAK2	-0.011	0.11	-9999	-0.65	1	1
positive regulation of chronic inflammatory response	-0.19	0.42	-9999	-0.86	226	226
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.017	0.035	-9999	-0.84	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
NFKB1	0.003	0.006	-9999	-10000	0	0
RELA	0.003	0.006	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.17	0.37	-9999	-0.99	78	78
ALOX12B	-0.17	0.38	-9999	-0.96	94	94
CXCL1	-0.35	0.64	-9999	-1.4	277	277
T cell proliferation	-0.19	0.42	-9999	-0.86	226	226
NFKBIA	0.003	0.006	-9999	-10000	0	0
IL17A	-0.072	0.24	-9999	-0.54	60	60
PI3K	-0.25	0.33	-9999	-0.83	186	186
IFNG	-0.005	0.026	-9999	-0.095	10	10
STAT3 (dimer)	-0.24	0.31	-9999	-0.86	142	142
IL18R1	-0.009	0.1	-9999	-0.8	17	17
IL23/IL23R/JAK2/TYK2/SOCS3	-0.086	0.24	-9999	-0.55	65	65
IL18/IL18R	-0.031	0.12	-9999	-0.54	53	53
macrophage activation	-0.014	0.017	-9999	-0.042	96	96
TNF	-0.18	0.41	-9999	-1.1	96	96
STAT3/STAT4	-0.26	0.35	-9999	-0.85	212	212
STAT4 (dimer)	-0.23	0.4	-9999	-0.88	215	215
IL18	-0.003	0.046	-9999	-0.29	25	25
IL19	-0.18	0.38	-9999	-0.92	119	119
STAT5A (dimer)	-0.22	0.38	-9999	-0.85	203	203
STAT1	-0.005	0.039	-9999	-0.29	19	19
SOCS3	-0.005	0.061	-9999	-0.8	6	6
CXCL9	-0.19	0.39	-9999	-0.93	124	124
MPO	-0.21	0.47	-9999	-1.2	140	140
positive regulation of humoral immune response	-0.19	0.42	-9999	-0.86	226	226
IL23/IL23R/JAK2/TYK2	-0.2	0.44	-9999	-0.89	225	225
IL6	-0.46	0.7	-9999	-1.3	388	388
STAT5A	-0.006	0.07	-9999	-0.8	8	8
IL2	0.004	0.028	-9999	-0.3	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.18	0.41	-9999	-0.99	125	125
keratinocyte proliferation	-0.19	0.42	-9999	-0.86	226	226
NOS2	-0.17	0.39	-9999	-0.9	129	129

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.22	0.27	-10000	0	-0.54	422	422
fibroblast growth factor receptor signaling pathway	-0.22	0.26	-10000	0	-0.54	422	422
LAMA1	-0.094	0.26	-10000	0	-0.79	123	123
PRNP	-0.012	0.099	-10000	0	-0.8	16	16
GPC1/SLIT2	-0.068	0.19	-10000	0	-0.62	113	113
SMAD2	0.01	0.11	-10000	0	-0.48	46	46
GPC1/PrPc/Cu2+	-0.01	0.069	-10000	0	-0.54	17	17
GPC1/Laminin alpha1	-0.073	0.2	-10000	0	-0.61	121	121
TDGF1	-0.008	0.079	-10000	0	-0.76	11	11
CRIPTO/GPC1	-0.008	0.064	-10000	0	-0.61	11	11
APP/GPC1	-0.001	0.023	-10000	0	-0.61	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.018	0.061	-10000	0	-0.53	12	12
FLT1	-0.001	0.025	-10000	0	-0.8	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.024	0.11	-10000	0	-0.53	46	46
SERPINC1	-0.016	0.066	-10000	0	-0.29	57	57
FYN	0.018	0.063	-10000	0	-0.53	13	13
FGR	0.018	0.061	-10000	0	-0.53	12	12
positive regulation of MAPKKK cascade	0.03	0.074	-10000	0	-0.53	13	13
SLIT2	-0.087	0.25	-10000	0	-0.8	112	112
GPC1/NRG	-0.23	0.3	-10000	0	-0.62	379	379
NRG1	-0.29	0.39	-10000	0	-0.8	378	378
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.029	-10000	0	-0.53	2	2
LYN	0.019	0.058	-10000	0	-0.53	11	11
mol:Spermine	0.01	0.024	-10000	0	-0.62	1	1
cell growth	-0.22	0.26	-10000	0	-0.54	422	422
BMP signaling pathway	0.002	0.032	0.37	6	-10000	0	6
SRC	0.019	0.058	-10000	0	-0.53	11	11
TGFBR1	0	0.009	-10000	0	-0.29	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.27	0.37	-10000	0	-0.77	362	362
GPC1	-0.002	0.032	-10000	0	-0.38	6	6
TGFBR1 (dimer)	0	0.009	-10000	0	-0.29	1	1
VEGFA	-0.003	0.03	-10000	0	-10000	0	0
BLK	-0.006	0.087	-10000	0	-0.57	13	13
HCK	0.017	0.061	-10000	0	-0.53	11	11
FGF2	-0.32	0.39	-10000	0	-0.8	416	416
FGFR1	-0.009	0.084	-10000	0	-0.69	14	14
VEGFR1 homodimer	-0.001	0.025	-10000	0	-0.8	1	1
TGFBR2	-0.035	0.16	-10000	0	-0.8	45	45
cell death	-0.001	0.023	-10000	0	-0.61	1	1
ATIII/GPC1	-0.012	0.048	-10000	0	-0.62	1	1
PLA2G2A/GPC1	-0.2	0.29	-10000	0	-0.62	336	336
LCK	0.006	0.09	-10000	0	-0.54	24	24
neuron differentiation	-0.23	0.29	-10000	0	-0.61	379	379
PrPc/Cu2+	-0.01	0.077	-10000	0	-0.62	16	16
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.035	0.16	-10000	0	-0.8	45	45

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.096	0.18	-10000	0	-0.48	185	185
ER alpha/Gai/GDP/Gbeta gamma	-0.092	0.19	-10000	0	-0.48	169	169
AKT1	-0.1	0.32	-10000	0	-0.84	161	161
PIK3CA	0	0.009	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.1	0.32	-10000	0	-0.86	158	158
mol:Ca2+	-0.028	0.15	-10000	0	-0.46	85	85
IGF1R	-0.021	0.12	-10000	0	-0.8	22	22
E2/ER alpha (dimer)/Striatin	-0.11	0.2	-10000	0	-0.55	174	174
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.094	0.3	0.8	161	-10000	0	161
RhoA/GTP	-0.071	0.14	-10000	0	-0.4	158	158
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.093	0.21	-10000	0	-0.54	167	167
regulation of stress fiber formation	0.024	0.14	0.46	11	-10000	0	11
E2/ERA-ERB (dimer)	-0.11	0.2	-10000	0	-0.55	177	177
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
G13/GTP	-0.091	0.18	-10000	0	-0.5	158	158
pseudopodium formation	-0.024	0.14	-10000	0	-0.46	11	11
E2/ER alpha (dimer)/PELP1	-0.099	0.19	-10000	0	-0.54	158	158
GRB2	0	0.009	-10000	0	-0.29	1	1
GNG2	-0.009	0.086	-10000	0	-0.8	12	12
GNAO1	-0.031	0.13	-10000	0	-0.48	66	66
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.06	0.22	-10000	0	-0.55	168	168
E2/ER beta (dimer)	-0.012	0.086	-10000	0	-0.62	20	20
mol:GDP	-0.087	0.21	-10000	0	-0.54	177	177
mol:NADP	-0.06	0.22	-10000	0	-0.55	168	168
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.03	0.15	-10000	0	-0.48	85	85
IGF-1R heterotetramer	-0.021	0.12	-10000	0	-0.8	22	22
PLCB1	-0.064	0.14	-10000	0	-0.5	84	84
PLCB2	-0.034	0.093	-10000	0	-0.67	14	14
IGF1	-0.18	0.33	-10000	0	-0.8	231	231
mol:L-citrulline	-0.06	0.22	-10000	0	-0.55	168	168
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.038	0.15	-10000	0	-0.85	25	25
JNK cascade	-0.012	0.085	-10000	0	-0.62	20	20
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.015	0.11	-10000	0	-0.8	20	20
GNAQ	-0.002	0.035	-10000	0	-0.8	2	2
ESR1	-0.16	0.29	-10000	0	-0.58	276	276
Gq family/GDP/Gbeta gamma	-0.007	0.071	-10000	0	-0.48	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.024	0.13	-10000	0	-0.32	158	158
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.093	0.21	-10000	0	-0.54	167	167
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.62	158	158
STRN	-0.015	0.11	-10000	0	-0.8	19	19
GNAL	-0.19	0.34	-10000	0	-0.8	244	244
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.006	0.082	-10000	0	-0.54	23	23
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	50	50
HBEGF	-0.069	0.19	-10000	0	-0.45	178	178
cAMP biosynthetic process	-0.19	0.26	-10000	0	-0.51	369	369
SRC	-0.051	0.2	-10000	0	-0.45	169	169
PI3K	-0.006	0.06	-10000	0	-0.61	10	10
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.079	0.19	-10000	0	-0.47	185	185
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.54	205	205
Gs family/GTP	-0.19	0.26	-10000	0	-0.53	369	369
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.014	-10000	0	-10000	0	0
vasodilation	-0.056	0.21	-10000	0	-0.52	168	168
mol:DAG	-0.03	0.15	-10000	0	-0.48	85	85
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.45	370	370
MSN	-0.028	0.15	-10000	0	-0.5	11	11
Gq family/GTP	-0.038	0.098	-10000	0	-0.64	16	16
mol:PI-3-4-5-P3	-0.099	0.31	-10000	0	-0.82	158	158
NRAS	-0.001	0.013	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.056	0.21	0.52	168	-10000	0	168
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.08	0.19	-10000	0	-0.5	177	177
NOS3	-0.065	0.24	-10000	0	-0.57	168	168
GNA11	-0.002	0.035	-10000	0	-0.8	2	2
MAPKKK cascade	-0.068	0.26	-10000	0	-0.64	174	174
E2/ER alpha (dimer)/PELP1/Src	-0.098	0.22	-10000	0	-0.57	167	167
ruffle organization	-0.024	0.14	-10000	0	-0.46	11	11
ROCK2	-0.075	0.14	-10000	0	-0.45	31	31
GNA14	-0.014	0.088	-10000	0	-0.46	31	31
GNA15	-0.003	0.034	-10000	0	-0.8	1	1
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.095	0.2	-10000	0	-0.48	176	176
MMP2	-0.043	0.19	-10000	0	-0.43	174	174

×

Aurora C 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
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.075	0.066	-9999	-0.62	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.019	0.017	-9999	-10000	0	0
AURKB	-0.17	0.14	-9999	-0.29	598	598
AURKC	-0.005	0.042	-9999	-0.32	15	15

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.046	-9999	-0.61	5	5
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.55	429	429
PTK2	-0.091	0.2	-9999	-0.67	43	43
IGF1R	-0.021	0.12	-9999	-0.8	22	22
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.092	-9999	-0.62	20	20
SRC	0	0.009	-9999	-0.29	1	1
CDKN1B	-0.089	0.13	-9999	-0.9	11	11
VEGFA	-0.003	0.03	-9999	-10000	0	0
ILK	-0.086	0.12	-9999	-0.84	8	8
ROCK1	-0.001	0.025	-9999	-0.8	1	1
AKT1	-0.076	0.11	-9999	-0.78	8	8
PTK2B	-0.019	0.095	-9999	-0.5	36	36
alphaV/beta3 Integrin/JAM-A	-0.21	0.25	-9999	-0.49	433	433
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.019	0.097	-9999	-0.53	35	35
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.26	-9999	-0.56	254	254
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.013	0.063	-9999	-0.44	10	10
alphaV/beta3 Integrin/Syndecan-1	-0.029	0.1	-9999	-0.54	36	36
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.33	0.36	-9999	-0.77	332	332
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Osteopontin	-0.056	0.11	-9999	-0.55	35	35
RPS6KB1	-0.3	0.32	-9999	-0.7	333	333
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.33	0.39	-9999	-0.77	429	429
GPR124	-0.009	0.086	-9999	-0.8	12	12
MAPK1	-0.33	0.39	-9999	-0.77	429	429
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
alphaV/beta3 Integrin/Tumstatin	-0.11	0.22	-9999	-0.55	214	214
cell adhesion	-0.023	0.11	-9999	-0.51	45	45
ANGPTL3	-0.001	0.018	-9999	-0.29	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.004	0.04	-9999	-0.53	5	5
IGF-1R heterotetramer	-0.021	0.12	-9999	-0.8	22	22
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.035	0.16	-9999	-0.8	45	45
ITGB3	-0.028	0.15	-9999	-0.75	39	39
IGF1	-0.18	0.33	-9999	-0.8	231	231
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.024	0.12	-9999	-0.6	41	41
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.025	-9999	-0.8	1	1
alphaV/beta3 Integrin/CD47	-0.019	0.097	-9999	-0.53	36	36
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.05	0.18	-9999	-0.67	74	74
CSF1	-0.005	0.066	-9999	-0.8	7	7
PIK3C2A	-0.087	0.12	-9999	-0.86	9	9
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.62	67	67
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.02	0.1	-9999	-0.54	36	36
FAK1/Vinculin	-0.066	0.16	-9999	-0.51	40	40
alphaV beta3/Integrin/ppsTEM5	-0.024	0.12	-9999	-0.6	41	41
RHOA	0	0	-9999	-10000	0	0
VTN	-0.026	0.1	-9999	-0.34	80	80
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.32	0.39	-9999	-0.8	416	416
F11R	-0.23	0.31	-9999	-0.61	416	416
alphaV/beta3 Integrin/Lactadherin	-0.026	0.12	-9999	-0.57	44	44
alphaV/beta3 Integrin/TGFBR2	-0.04	0.17	-9999	-0.68	61	61
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.039	-9999	-0.48	7	7
HSP90AA1	0	0.009	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.017	0.089	-9999	-0.49	35	35
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.14	-9999	-0.29	414	414
alphaV/beta3 Integrin/Pyk2	-0.019	0.096	-9999	-0.5	36	36
SDC1	-0.021	0.078	-9999	-0.3	74	74
VAV3	-0.008	0.053	-9999	-0.45	14	14
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.8	43	43
FAK1/Paxillin	-0.066	0.16	-9999	-0.51	40	40
cell migration	-0.052	0.15	-9999	-0.45	40	40
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.23	-9999	-0.44	435	435
SPP1	-0.077	0.13	-9999	-0.29	277	277
KDR	-0.004	0.056	-9999	-0.8	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.14	0.31	-9999	-0.79	190	190
angiogenesis	-0.3	0.39	-9999	-0.75	431	431
Rac1/GTP	-0.007	0.048	-9999	-0.41	14	14
EDIL3	-0.051	0.19	-9999	-0.7	75	75
cell proliferation	-0.04	0.17	-9999	-0.67	61	61

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.05	-10000	0	-0.8	4	4
Jak2/Leptin Receptor	-0.16	0.24	-10000	0	-0.53	280	280
PTP1B/AKT1	-0.069	0.11	-10000	0	-0.34	106	106
FYN	-0.002	0.035	-10000	0	-0.8	2	2
p210 bcr-abl/PTP1B	-0.07	0.13	-10000	0	-0.39	108	108
EGFR	-0.3	0.39	-10000	0	-0.81	383	383
EGF/EGFR	-0.29	0.31	-10000	0	-0.57	521	521
CSF1	-0.005	0.066	-10000	0	-0.8	7	7
AKT1	0	0.002	-10000	0	-10000	0	0
INSR	0	0.009	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.097	0.12	-10000	0	-0.37	112	112
Insulin Receptor/Insulin	-0.049	0.08	-10000	0	-0.41	19	19
HCK	-0.004	0.032	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.059	0.12	-10000	0	-0.37	106	106
EGF	-0.16	0.32	-10000	0	-0.81	202	202
YES1	-0.001	0.025	-10000	0	-0.8	1	1
CAV1	-0.17	0.24	-10000	0	-0.51	277	277
TXN	0	0.016	-10000	0	-0.29	3	3
PTP1B/IRS1/GRB2	-0.086	0.14	-10000	0	-0.5	79	79
cell migration	0.07	0.13	0.39	108	-10000	0	108
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.005	0.066	-10000	0	-0.53	13	13
ITGA2B	-0.018	0.078	-10000	0	-0.81	3	3
CSF1R	-0.001	0.026	-10000	0	-0.55	2	2
Prolactin Receptor/Prolactin	-0.006	0.054	-10000	0	-0.62	6	6
FGR	-0.001	0.026	-10000	0	-0.8	1	1
PTP1B/p130 Cas	-0.074	0.11	-10000	0	-0.37	106	106
Crk/p130 Cas	-0.068	0.11	-10000	0	-0.36	94	94
DOK1	-0.045	0.12	-10000	0	-0.33	91	91
JAK2	-0.041	0.079	-10000	0	-0.33	24	24
Jak2/Leptin Receptor/Leptin	-0.37	0.18	-10000	0	-0.48	594	594
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
PTPN1	-0.071	0.13	-10000	0	-0.39	108	108
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.055	0.12	-10000	0	-0.3	193	193
SRC	-0.013	0.047	-10000	0	-10000	0	0
ITGB3	-0.028	0.15	-10000	0	-0.77	38	38
CAT1/PTP1B	-0.084	0.17	-10000	0	-0.48	77	77
CAPN1	0	0.009	-10000	0	-0.29	1	1
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.043	0.09	-10000	0	-0.54	16	16
mol:H2O2	-0.005	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.33	0.16	-10000	0	-0.44	521	521
negative regulation of transcription	-0.04	0.078	-10000	0	-0.32	24	24
FCGR2A	0	0.009	-10000	0	-0.29	1	1
FER	-0.008	0.084	-10000	0	-0.82	11	11
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.63	38	38
BLK	-0.041	0.11	-10000	0	-0.3	142	142
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0.001	0.003	-10000	0	-10000	0	0
LEPR	-0.21	0.36	-10000	0	-0.81	276	276
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-0.29	1	1
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.031	0.13	-10000	0	-0.51	15	15
PRL	-0.004	0.033	-10000	0	-0.29	13	13
SOCS3	0.017	0.12	-10000	0	-1.5	6	6
SPRY2	-0.091	0.26	-10000	0	-0.82	116	116
Insulin Receptor/Insulin/IRS1	-0.023	0.11	-10000	0	-0.55	43	43
CSF1/CSF1R	-0.071	0.12	-10000	0	-0.36	110	110
Ras protein signal transduction	0.037	0.036	-10000	0	-10000	0	0
IRS1	-0.033	0.16	-10000	0	-0.8	43	43
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.65	0.32	-10000	0	-0.8	839	839
STAT5B	-0.057	0.11	-10000	0	-0.32	110	110
STAT5A	-0.058	0.11	-10000	0	-0.32	113	113
GRB2	0	0.009	-10000	0	-0.29	1	1
PDGFB-D/PDGFRB	-0.076	0.12	-10000	0	-0.38	108	108
CSN2	0.018	0.034	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
LAT	-0.014	0.053	-10000	0	-0.58	2	2
YBX1	-0.001	0.014	-10000	0	-10000	0	0
LCK	-0.02	0.1	-10000	0	-0.43	49	49
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.004	0.046	-10000	0	-0.81	2	2

×

amb2 Integrin signaling

Figure S38. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S38. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.062	-9999	-0.58	10	10
alphaM/beta2 Integrin/GPIbA	-0.025	0.059	-9999	-0.53	9	9
alphaM/beta2 Integrin/proMMP-9	-0.082	0.081	-9999	-0.34	17	17
PLAUR	-0.021	0.074	-9999	-10000	0	0
HMGB1	-0.013	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.018	0.028	-9999	-10000	0	0
AGER	-0.015	0.041	-9999	-0.86	2	2
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.075	0.097	-9999	-0.7	2	2
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.29	453	453
CYR61	-0.044	0.18	-9999	-0.8	57	57
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.058	0.11	-9999	-0.53	21	21
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.34	-9999	-0.8	243	243
MYH2	-0.07	0.16	-9999	-0.4	113	113
MST1R	-0.011	0.086	-9999	-0.57	20	20
leukocyte activation during inflammatory response	-0.3	0.23	-9999	-0.48	636	636
APOB	-0.49	0.39	-9999	-0.8	636	636
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.079	-9999	-0.8	10	10
JAM3	-0.005	0.066	-9999	-0.8	7	7
GP1BA	-0.012	0.079	-9999	-0.4	32	32
alphaM/beta2 Integrin/CTGF	-0.025	0.07	-9999	-0.59	13	13
alphaM/beta2 Integrin	-0.073	0.13	-9999	-0.37	85	85
JAM3 homodimer	-0.005	0.066	-9999	-0.8	7	7
ICAM2	-0.004	0.056	-9999	-0.8	5	5
ICAM1	-0.004	0.035	-9999	-0.29	15	15
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.062	0.14	-9999	-0.37	85	85
cell adhesion	-0.025	0.059	-9999	-0.53	9	9
NFKB1	-0.14	0.18	-9999	-0.66	14	14
THY1	-0.002	0.024	-9999	-0.29	7	7
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.34	0.27	-9999	-0.55	636	636
alphaM/beta2 Integrin/LRP/tPA	-0.035	0.11	-9999	-0.56	43	43
IL6	-0.3	0.48	-9999	-0.94	380	380
ITGB2	-0.017	0.037	-9999	-0.3	14	14
elevation of cytosolic calcium ion concentration	-0.024	0.048	-9999	-0.39	1	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.043	0.13	-9999	-0.55	61	61
JAM2	-0.046	0.19	-9999	-0.8	59	59
alphaM/beta2 Integrin/ICAM1	-0.022	0.083	-9999	-0.54	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.032	-9999	-10000	0	0
RhoA/GTP	-0.089	0.16	-9999	-0.39	186	186
positive regulation of phagocytosis	-0.049	0.09	-9999	-0.46	18	18
Ron/MSP	-0.017	0.1	-9999	-0.67	22	22
alphaM/beta2 Integrin/uPAR/uPA	-0.024	0.048	-9999	-0.4	1	1
alphaM/beta2 Integrin/uPAR	-0.028	0.046	-9999	-0.44	1	1
PLAU	-0.008	0.047	-9999	-0.29	28	28
PLAT	-0.029	0.15	-9999	-0.76	39	39
actin filament polymerization	-0.067	0.16	-9999	-0.39	113	113
MST1	-0.012	0.092	-9999	-0.64	19	19
alphaM/beta2 Integrin/lipoprotein(a)	-0.3	0.23	-9999	-0.48	636	636
TNF	-0.089	0.22	-9999	-0.96	18	18
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.021	0.036	-9999	-0.29	1	1
fibrinolysis	-0.019	0.032	-9999	-10000	0	0
HCK	-0.004	0.032	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.062	0.14	-9999	-0.37	85	85
VTN	-0.026	0.1	-9999	-0.34	80	80
alphaM/beta2 Integrin/CYR61	-0.047	0.13	-9999	-0.58	57	57
LPA	-0.001	0.02	-9999	-0.29	5	5
LRP1	-0.009	0.082	-9999	-0.8	11	11
cell migration	-0.071	0.083	-9999	-0.48	15	15
FN1	-0.12	0.14	-9999	-0.29	414	414
alphaM/beta2 Integrin/Thy1	-0.019	0.031	-9999	-10000	0	0
MPO	-0.055	0.2	-9999	-0.78	73	73
KNG1	-0.005	0.039	-9999	-0.29	19	19
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.066	0.16	-9999	-0.4	109	109
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.02	-9999	-0.29	5	5
CTGF	-0.011	0.091	-9999	-0.71	16	16
alphaM/beta2 Integrin/Hck	-0.019	0.035	-9999	-10000	0	0
ITGAM	-0.015	0.028	-9999	-0.3	6	6
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.21	-9999	-0.51	243	243
HP	-0.16	0.31	-9999	-0.8	194	194
leukocyte adhesion	-0.076	0.13	-9999	-0.6	41	41
SELP	-0.19	0.34	-9999	-0.8	243	243

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.065	0.22	-9999	-0.68	40	40
CRP	-0.069	0.22	-9999	-0.68	40	40
cell cycle arrest	-0.083	0.25	-9999	-0.72	67	67
TIMP1	-0.062	0.21	-9999	-0.56	64	64
IL6ST	-0.083	0.26	-9999	-0.8	124	124
Rac1/GDP	-0.13	0.23	-9999	-0.68	88	88
AP1	-0.13	0.24	-9999	-0.47	307	307
GAB2	0.004	0.045	-9999	-0.38	11	11
TNFSF11	-0.075	0.22	-9999	-0.66	48	48
HSP90B1	0.015	0.047	-9999	-10000	0	0
GAB1	0	0.002	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.76	82	82
AKT1	0.038	0.04	-9999	-10000	0	0
FOXO1	0.047	0.057	-9999	-0.42	10	10
MAP2K6	-0.15	0.26	-9999	-0.72	103	103
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.087	0.23	-9999	-0.64	84	84
MITF	-0.14	0.26	-9999	-0.72	95	95
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.014	0.12	-9999	-1.5	7	7
CEBPB	0.016	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.056	0.084	-9999	-0.44	10	10
STAT3	-0.092	0.26	-9999	-0.79	67	67
STAT1	-0.013	0.022	-9999	-10000	0	0
CEBPD	-0.067	0.22	-9999	-0.67	54	54
PIK3CA	0.012	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.06	-9999	-0.61	10	10
JUN	-0.005	0.066	-9999	-0.8	7	7
PIAS3/MITF	-0.16	0.22	-9999	-0.72	84	84
MAPK11	-0.13	0.25	-9999	-0.77	83	83
STAT3 (dimer)/FOXO1	-0.035	0.22	-9999	-0.59	63	63
GRB2/SOS1/GAB family	-0.14	0.2	-9999	-0.72	68	68
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.16	0.26	-9999	-0.51	209	209
GRB2	0	0.009	-9999	-0.29	1	1
JAK2	-0.001	0.025	-9999	-0.8	1	1
LBP	-0.24	0.45	-9999	-0.97	259	259
PIK3R1	0.003	0.08	-9999	-0.8	10	10
JAK1	0.003	0.026	-9999	-0.8	1	1
MYC	-0.078	0.26	-9999	-0.82	63	63
FGG	-0.075	0.22	-9999	-0.69	40	40
macrophage differentiation	-0.083	0.25	-9999	-0.72	67	67
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.28	-9999	-0.51	472	472
JUNB	-0.064	0.21	-9999	-0.61	58	58
FOS	-0.24	0.37	-9999	-0.8	307	307
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.16	0.26	-9999	-0.52	220	220
STAT1/PIAS1	-0.14	0.22	-9999	-0.59	119	119
GRB2/SOS1/GAB family/SHP2/PI3K	-0.002	0.031	-9999	-0.29	5	5
STAT3 (dimer)	-0.087	0.26	-9999	-0.76	67	67
PRKCD	-0.061	0.22	-9999	-0.61	76	76
IL6R	-0.028	0.16	-9999	-0.8	40	40
SOCS3	-0.12	0.24	-9999	-0.75	80	80
gp130 (dimer)/JAK1/JAK1/LMO4	-0.056	0.18	-9999	-0.53	126	126
Rac1/GTP	-0.15	0.21	-9999	-0.68	88	88
HCK	-0.004	0.032	-9999	-10000	0	0
MAPKKK cascade	-0.006	0.085	-9999	-1	2	2
bone resorption	-0.071	0.21	-9999	-0.61	55	55
IRF1	-0.065	0.22	-9999	-0.63	60	60
mol:GDP	-0.13	0.25	-9999	-0.65	109	109
SOS1	0	0.003	-9999	-10000	0	0
VAV1	-0.14	0.26	-9999	-0.67	106	106
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.17	0.25	-9999	-0.82	85	85
PTPN11	-0.014	0.02	-9999	-10000	0	0
IL6/IL6RA	-0.24	0.32	-9999	-0.64	398	398
gp130 (dimer)/TYK2/TYK2/LMO4	-0.058	0.18	-9999	-0.53	126	126
gp130 (dimer)/JAK2/JAK2/LMO4	-0.058	0.18	-9999	-0.53	126	126
IL6	-0.28	0.39	-9999	-0.8	381	381
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.003	0.026	-9999	-0.81	1	1
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-9999	-0.41	471	471
LMO4	0.009	0.051	-9999	-0.8	3	3
STAT3 (dimer)/PIAS3	-0.15	0.21	-9999	-0.79	67	67
MCL1	0.051	0.032	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.023	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.039	-9999	-0.31	2	2
PDE6G/GNAT1/GTP	-0.009	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.035	-9999	-10000	0	0
GRK1	-0.003	0.028	-9999	-0.29	10	10
CNG Channel	-0.14	0.2	-9999	-0.44	302	302
mol:Na +	-0.13	0.19	-9999	-0.43	297	297
mol:ADP	-0.003	0.028	-9999	-0.29	10	10
RGS9-1/Gbeta5/R9AP	-0.064	0.16	-9999	-0.54	104	104
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.14	0.2	-9999	-0.44	297	297
CNGB1	-0.015	0.064	-9999	-10000	0	0
RDH5	-0.48	0.4	-9999	-0.8	614	614
SAG	-0.014	0.063	-9999	-0.29	51	51
mol:Ca2+	-0.12	0.18	-9999	-0.54	24	24
Na + (4 Units)	-0.12	0.18	-9999	-0.52	24	24
RGS9	-0.084	0.24	-9999	-0.74	118	118
GNB1/GNGT1	-0.029	0.067	-9999	-10000	0	0
GNAT1/GDP	-0.057	0.14	-9999	-0.47	104	104
GUCY2D	-0.007	0.06	-9999	-0.8	4	4
GNGT1	-0.046	0.11	-9999	-0.29	165	165
GUCY2F	-0.001	0.013	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.019	0.071	-9999	-0.46	21	21
mol:11-cis-retinal	-0.48	0.39	-9999	-0.8	614	614
mol:cGMP	-0.011	0.051	-9999	-0.46	9	9
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.37	0.3	-9999	-0.62	614	614
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.23	0.36	-9999	-0.8	297	297
Metarhodopsin II	-0.003	0.021	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.012	0.054	-9999	-0.49	9	9
RGS9BP	-0.019	0.072	-9999	-0.29	68	68
Metarhodopsin II/Transducin	-0.009	0.02	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.044	-9999	-0.5	5	5
PDE6A/B	-0.017	0.091	-9999	-0.62	21	21
mol:Pi	-0.064	0.16	-9999	-0.54	104	104
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.023	0.05	-9999	-10000	0	0
PDE6B	-0.017	0.11	-9999	-0.74	24	24
PDE6A	-0.006	0.043	-9999	-10000	0	0
PDE6G	-0.013	0.059	-9999	-10000	0	0
RHO	-0.004	0.035	-9999	-0.29	15	15
PDE6	-0.065	0.15	-9999	-0.46	121	121
GUCA1A	-0.013	0.059	-9999	-0.29	45	45
GC2/GCAP Family	-0.009	0.044	-9999	-0.5	5	5
GUCA1C	0	0.009	-9999	-0.29	1	1
GUCA1B	-0.004	0.056	-9999	-0.8	5	5

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.055	0.16	-9999	-0.54	104	104
EFNA5	-0.081	0.24	-9999	-0.8	105	105
FYN	-0.034	0.16	-9999	-0.5	105	105
neuron projection morphogenesis	-0.055	0.16	-9999	-0.54	104	104
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.055	0.16	-9999	-0.54	104	104
EPHA5	-0.001	0.018	-9999	-0.29	4	4

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.036	0.16	-9999	-0.43	20	20
RXRs/LXRs/DNA/Oxysterols	-0.016	0.15	-9999	-0.5	19	19
MED1	-0.007	0.044	-9999	-0.29	24	24
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.023	0.092	-9999	-0.36	65	65
RXRs/NUR77	-0.15	0.24	-9999	-0.51	312	312
RXRs/PPAR	-0.13	0.23	-9999	-0.38	427	427
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.007	0.052	-9999	-0.46	13	13
RARA	-0.004	0.033	-9999	-0.29	14	14
NCOA1	-0.001	0.025	-9999	-0.8	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.007	0.053	-9999	-0.46	13	13
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.022	0.088	-9999	-0.35	65	65
THRA	-0.001	0.025	-9999	-0.8	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.2	-9999	-0.48	256	256
NR1H4	-0.003	0.03	-9999	-0.29	11	11
RXRs/LXRs/DNA	-0.11	0.19	-9999	-0.43	256	256
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.19	-9999	-0.45	256	256
NR4A1	-0.063	0.22	-9999	-0.8	81	81
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.045	0.13	-9999	-0.27	256	256
RXRG	-0.19	0.35	-9999	-0.79	259	259
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.016	0.007	-9999	-10000	0	0
THRB	-0.043	0.18	-9999	-0.8	56	56
PPARG	-0.19	0.34	-9999	-0.8	243	243
PPARD	0	0	-9999	-10000	0	0
TNF	-0.018	0.19	-9999	-1.2	15	15
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.016	0.15	-9999	-0.5	19	19
PPARA	-0.005	0.061	-9999	-0.8	6	6
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.089	-9999	-0.8	13	13
RXRs/NUR77/BCL2	-0.12	0.19	-9999	-0.38	334	334
SREBF1	-0.006	0.14	-9999	-0.63	8	8
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-9999	-0.48	256	256
ABCA1	-0.01	0.16	-9999	-1	10	10
RARs/THRs	-0.032	0.12	-9999	-0.48	65	65
RXRs/FXR	-0.12	0.21	-9999	-0.48	256	256
BCL2	-0.028	0.15	-9999	-0.8	36	36

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.027	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.18	0.2	-9999	-0.41	458	458
Syndecan-3/Neurocan	-0.007	0.027	-9999	-10000	0	0
POMC	-0.024	0.12	-9999	-0.48	51	51
EGFR	-0.29	0.39	-9999	-0.8	383	383
Syndecan-3/EGFR	-0.16	0.22	-9999	-0.45	378	378
AGRP	-0.003	0.028	-9999	-0.29	10	10
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.009	-9999	-0.29	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.025	-9999	-0.8	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.072	-9999	-0.29	68	68
long-term memory	-0.002	0.021	-9999	-0.42	2	2
Syndecan-3/IL8	-0.016	0.067	-9999	-0.45	20	20
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.002	0.035	-9999	-0.8	2	2
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.004	0.032	-9999	-0.29	13	13
SRC	0	0.009	-9999	-0.29	1	1
PTN	-0.36	0.4	-9999	-0.8	460	460
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.18	0.2	-9999	-0.4	458	458
Syndecan-3/AgRP	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.015	-9999	-10000	0	0
Fyn/Cortactin	-0.003	0.032	-9999	-0.61	2	2
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.015	0.066	-9999	-0.44	20	20
IL8	-0.033	0.13	-9999	-0.41	84	84
Syndecan-3/Fyn/Cortactin	-0.002	0.021	-9999	-0.43	2	2
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.019	0.092	-9999	-0.6	21	21
Gamma Secretase	-0.001	0.014	-9999	-0.45	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

Figure S44. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S44. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.095	0.2	0.64	110	-10000	0	110
KIRREL	-0.084	0.25	-10000	0	-0.81	110	110
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.095	0.2	-10000	0	-0.64	110	110
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.069	0.15	-10000	0	-0.49	110	110
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.042	0.11	-10000	0	-0.36	110	110
FYN	-0.064	0.15	-10000	0	-0.47	110	110
mol:Ca2+	-0.068	0.15	-10000	0	-0.49	110	110
mol:DAG	-0.069	0.15	-10000	0	-0.49	110	110
NPHS2	-0.008	0.031	-10000	0	-0.29	5	5
mol:IP3	-0.069	0.15	-10000	0	-0.49	110	110
regulation of endocytosis	-0.054	0.14	-10000	0	-0.44	110	110
Nephrin/NEPH1/podocin/Cholesterol	-0.071	0.16	-10000	0	-0.5	110	110
establishment of cell polarity	-0.095	0.2	-10000	0	-0.64	110	110
Nephrin/NEPH1/podocin/NCK1-2	-0.056	0.14	-10000	0	-0.45	110	110
Nephrin/NEPH1/beta Arrestin2	-0.055	0.14	-10000	0	-0.45	110	110
NPHS1	-0.051	0.11	-10000	0	-0.36	17	17
Nephrin/NEPH1/podocin	-0.064	0.15	-10000	0	-0.48	110	110
TJP1	-0.001	0.025	-10000	0	-0.8	1	1
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.069	0.15	-10000	0	-0.49	110	110
CD2AP	0	0.009	-10000	0	-0.29	1	1
Nephrin/NEPH1/podocin/GRB2	-0.069	0.15	-10000	0	-0.49	110	110
GRB2	0	0.009	-10000	0	-0.29	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.073	0.17	-10000	0	-0.51	118	118
cytoskeleton organization	-0.054	0.14	-10000	0	-0.46	110	110
Nephrin/NEPH1	-0.069	0.15	-10000	0	-0.48	110	110
Nephrin/NEPH1/ZO-1	-0.075	0.16	-10000	0	-0.53	110	110

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.018	0.094	-9999	-0.52	32	32
NF kappa B1 p50/RelA/I kappa B alpha	-0.044	0.11	-9999	-0.48	5	5
AP1	-0.19	0.25	-9999	-0.48	400	400
mol:PIP3	-0.2	0.25	-9999	-0.47	387	387
AKT1	-0.015	0.073	-9999	-0.59	7	7
PTK2B	0.014	0.061	-9999	-0.3	21	21
RHOA	0.029	0.027	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.007	0.13	-9999	-0.36	122	122
MAGI3	-0.001	0.025	-9999	-0.8	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.062	0.15	-9999	-0.43	139	139
HRAS/GDP	-0.002	0.018	-9999	-0.2	9	9
positive regulation of microtubule depolymerization	-0.02	0.15	-9999	-0.41	117	117
NF kappa B1 p50/RelA	-0.054	0.14	-9999	-0.64	9	9
endothelial cell migration	0.008	0.12	-9999	-0.65	30	30
ADCY4	-0.001	0.15	-9999	-0.65	35	35
ADCY5	-0.071	0.19	-9999	-0.61	72	72
ADCY6	0.008	0.13	-9999	-0.61	28	28
ADCY7	0.008	0.13	-9999	-0.61	28	28
ADCY1	0	0.14	-9999	-0.64	34	34
ADCY2	-0.011	0.16	-9999	-0.63	41	41
ADCY3	0.008	0.13	-9999	-0.61	28	28
ADCY8	0.005	0.13	-9999	-0.62	28	28
ADCY9	0.008	0.13	-9999	-0.61	28	28
GSK3B	0.021	0.058	-9999	-0.36	9	9
arachidonic acid secretion	0.011	0.12	-9999	-0.56	31	31
GNG2	-0.009	0.086	-9999	-0.8	12	12
TRIP6	-0.001	0.017	-9999	-0.52	1	1
GNAO1	-0.006	0.13	-9999	-0.53	52	52
HRAS	-0.003	0.027	-9999	-0.29	9	9
NFKBIA	-0.004	0.15	-9999	-0.4	122	122
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.004	-9999	-10000	0	0
JUN	-0.005	0.066	-9999	-0.8	7	7
LPA/LPA2/NHERF2	-0.002	0.016	-9999	-10000	0	0
TIAM1	0.001	0.004	-9999	-10000	0	0
PIK3R1	-0.008	0.078	-9999	-0.8	10	10
mol:IP3	-0.008	0.13	-9999	-0.36	122	122
PLCB3	0.024	0.018	-9999	-10000	0	0
FOS	-0.24	0.37	-9999	-0.8	307	307
positive regulation of mitosis	0.011	0.12	-9999	-0.56	31	31
LPA/LPA1-2-3	-0.074	0.17	-9999	-0.5	139	139
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.002	0.1	-9999	-0.39	22	22
GNAZ	0.009	0.1	-9999	-0.49	38	38
EGFR/PI3K-beta/Gab1	-0.21	0.26	-9999	-0.64	161	161
positive regulation of dendritic cell cytokine production	-0.073	0.17	-9999	-0.49	139	139
LPA/LPA2/MAGI-3	-0.002	0.02	-9999	-0.53	1	1
ARHGEF1	-0.01	0.068	-9999	-0.45	21	21
GNAI2	0.013	0.086	-9999	-0.47	30	30
GNAI3	0.013	0.086	-9999	-0.47	30	30
GNAI1	-0.013	0.15	-9999	-0.55	73	73
LPA/LPA3	-0.081	0.2	-9999	-0.62	122	122
LPA/LPA2	-0.002	0.016	-9999	-10000	0	0
LPA/LPA1	-0.016	0.095	-9999	-0.55	30	30
HB-EGF/EGFR	-0.26	0.26	-9999	-0.58	383	383
HBEGF	-0.069	0.11	-9999	-0.62	3	3
mol:DAG	-0.008	0.13	-9999	-0.36	122	122
cAMP biosynthetic process	-0.01	0.15	-9999	-0.57	50	50
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
GNB1	0	0	-9999	-10000	0	0
LYN	-0.004	0.15	-9999	-0.4	122	122
GNAQ	-0.054	0.13	-9999	-0.42	124	124
LPAR2	-0.001	0.016	-9999	-0.29	3	3
LPAR3	-0.11	0.26	-9999	-0.8	122	122
LPAR1	-0.018	0.11	-9999	-0.8	21	21
IL8	-0.19	0.23	-9999	-0.44	403	403
PTK2	-0.068	0.16	-9999	-0.46	139	139
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.062	0.15	-9999	-0.43	139	139
EGFR	-0.29	0.39	-9999	-0.8	383	383
PLCG1	-0.031	0.15	-9999	-0.43	122	122
PLD2	-0.068	0.16	-9999	-0.46	139	139
G12/G13	-0.012	0.074	-9999	-0.49	21	21
PI3K-beta	-0.017	0.086	-9999	-0.72	7	7
cell migration	-0.021	0.054	-9999	-0.24	7	7
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
PXN	0.002	0.1	-9999	-0.4	22	22
HRAS/GTP	-0.033	0.12	-9999	-0.58	31	31
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.29	453	453
PRKCE	0	0.001	-9999	-10000	0	0
PRKCD	0	0.13	-9999	-0.39	10	10
Gi(beta/gamma)	-0.034	0.12	-9999	-0.58	35	35
mol:LPA	-0.002	0.02	-9999	-0.22	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.056	0.14	-9999	-0.64	10	10
MAPKKK cascade	0.011	0.12	-9999	-0.56	31	31
contractile ring contraction involved in cytokinesis	0.029	0.026	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.059	0.14	-9999	-0.43	130	130
GNA15	-0.054	0.13	-9999	-0.42	123	123
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.022	0.15	-9999	-0.43	117	117
GNA11	-0.054	0.13	-9999	-0.42	124	124
Rac1/GTP	0.001	0.005	-9999	-10000	0	0
MMP2	0.008	0.12	-9999	-0.65	30	30

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.054	0.3	-10000	0	-0.82	124	124
IHH	-0.014	0.082	-10000	0	-0.46	6	6
SHH Np/Cholesterol/GAS1	-0.03	0.12	-10000	0	-0.5	57	57
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.03	0.11	0.5	57	-10000	0	57
SMO/beta Arrestin2	-0.076	0.23	-10000	0	-0.85	78	78
SMO	-0.037	0.26	-10000	0	-0.91	78	78
AKT1	0.008	0.11	-10000	0	-0.33	77	77
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.06	0.21	-10000	0	-0.8	78	78
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.035	0.26	-10000	0	-0.88	78	78
STIL	-0.04	0.21	-10000	0	-0.71	80	80
DHH N/PTCH2	-0.066	0.2	-10000	0	-0.64	105	105
DHH N/PTCH1	-0.09	0.24	-10000	0	-0.78	101	101
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DHH	-0.023	0.13	-10000	0	-0.8	29	29
PTHLH	-0.082	0.38	-10000	0	-1.1	124	124
determination of left/right symmetry	-0.035	0.26	-10000	0	-0.88	78	78
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
skeletal system development	-0.079	0.37	-10000	0	-1	124	124
IHH N/Hhip	-0.014	0.046	-10000	0	-0.66	1	1
DHH N/Hhip	-0.02	0.11	-10000	0	-0.62	30	30
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.035	0.26	-10000	0	-0.88	78	78
pancreas development	-0.004	0.038	-10000	0	-0.34	11	11
HHAT	-0.001	0.025	-10000	0	-0.8	1	1
PI3K	-0.006	0.06	-10000	0	-0.61	10	10
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.043	0.18	-10000	0	-0.8	56	56
somite specification	-0.035	0.26	-10000	0	-0.88	78	78
SHH Np/Cholesterol/PTCH1	-0.072	0.21	-10000	0	-0.76	77	77
SHH Np/Cholesterol/PTCH2	-0.042	0.14	-10000	0	-0.5	83	83
SHH Np/Cholesterol/Megalin	-0.14	0.22	-10000	0	-0.5	272	272
SHH	0.01	0.036	-10000	0	-0.62	1	1
catabolic process	-0.048	0.26	-10000	0	-0.86	86	86
SMO/Vitamin D3	-0.075	0.23	-10000	0	-0.82	78	78
SHH Np/Cholesterol/Hhip	-0.005	0.034	-10000	0	-0.5	2	2
LRP2	-0.22	0.35	-10000	0	-0.8	271	271
receptor-mediated endocytosis	-0.15	0.25	-10000	0	-0.83	94	94
SHH Np/Cholesterol/BOC	-0.041	0.13	-10000	0	-0.5	79	79
SHH Np/Cholesterol/CDO	-0.01	0.06	-10000	0	-0.49	14	14
mesenchymal cell differentiation	0.005	0.034	0.5	2	-10000	0	2
mol:Vitamin D3	-0.031	0.22	-10000	0	-0.77	77	77
IHH N/PTCH2	-0.065	0.19	-10000	0	-0.67	86	86
CDON	-0.01	0.089	-10000	0	-0.8	13	13
IHH N/PTCH1	-0.046	0.26	-10000	0	-0.87	86	86
Megalin/LRPAP1	-0.16	0.27	-10000	0	-0.61	271	271
PTCH2	-0.064	0.22	-10000	0	-0.8	82	82
SHH Np/Cholesterol	-0.004	0.026	-10000	0	-0.5	1	1
PTCH1	-0.048	0.26	-10000	0	-0.87	86	86
HHIP	-0.004	0.038	-10000	0	-0.34	11	11

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.049	0.2	-9999	-0.82	65	65
PDGF/PDGFRA/CRKL	-0.038	0.15	-9999	-0.62	64	64
positive regulation of JUN kinase activity	-0.029	0.11	-9999	-0.47	64	64
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.042	0.15	-9999	-0.62	64	64
AP1	-0.36	0.54	-9999	-1.2	307	307
mol:IP3	-0.033	0.16	-9999	-0.64	64	64
PLCG1	-0.033	0.16	-9999	-0.64	64	64
PDGF/PDGFRA/alphaV Integrin	-0.038	0.15	-9999	-0.62	64	64
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.033	0.16	-9999	-0.64	64	64
CAV3	-0.001	0.016	-9999	-0.29	3	3
CAV1	-0.17	0.33	-9999	-0.8	224	224
SHC/Grb2/SOS1	-0.03	0.12	-9999	-0.48	64	64
PDGF/PDGFRA/Shf	-0.039	0.15	-9999	-0.62	64	64
FOS	-0.32	0.55	-9999	-1.1	341	341
JUN	-0.024	0.061	-9999	-0.68	7	7
oligodendrocyte development	-0.038	0.15	-9999	-0.62	64	64
GRB2	0	0.009	-9999	-0.29	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:DAG	-0.033	0.16	-9999	-0.64	64	64
PDGF/PDGFRA	-0.049	0.2	-9999	-0.82	65	65
actin cytoskeleton reorganization	-0.039	0.15	-9999	-0.62	65	65
SRF	0.015	0.021	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.038	0.14	-9999	-0.54	73	73
PDGF/PDGFRA/Crk/C3G	-0.033	0.13	-9999	-0.53	64	64
JAK1	-0.023	0.15	-9999	-0.62	65	65
ELK1/SRF	-0.026	0.12	-9999	-0.48	64	64
SHB	-0.001	0.026	-9999	-0.8	1	1
SHF	-0.001	0.026	-9999	-0.55	2	2
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.034	0.16	-9999	-0.66	64	64
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.029	0.11	-9999	-0.47	64	64
PDGF/PDGFRA/SHB	-0.039	0.15	-9999	-0.62	65	65
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.72	246	246
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.033	0.15	-9999	-0.59	64	64
PIK3CA	0	0.009	-9999	-0.29	1	1
PDGF/PDGFRA/Crk	-0.038	0.15	-9999	-0.62	64	64
JAK-STAT cascade	-0.022	0.15	-9999	-0.62	65	65
cell proliferation	-0.039	0.15	-9999	-0.62	64	64

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.028	0.03	-9999	-10000	0	0
BUB1B	-0.038	0.051	-9999	-10000	0	0
PLK1	-0.007	0.023	-9999	-10000	0	0
PLK1S1	0.001	0.013	-9999	-10000	0	0
KIF2A	0.002	0.021	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.008	0.023	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.17	0.12	-9999	-0.28	506	506
WEE1	-0.002	0.023	-9999	-10000	0	0
cytokinesis	-0.053	0.056	-9999	-0.24	28	28
PP2A-alpha B56	0.029	0.02	-9999	-10000	0	0
AURKA	0	0.014	-9999	-10000	0	0
PICH/PLK1	-0.075	0.095	-9999	-0.34	11	11
CENPE	-0.05	0.085	-9999	-0.17	173	173
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.002	0.021	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.005	0.016	-9999	-10000	0	0
PAK1	-0.007	0.043	-9999	-0.28	24	24
SPC24	-0.18	0.14	-9999	-0.29	645	645
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.005	0.018	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.004	0.013	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.025	-9999	-0.8	1	1
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.008	0.023	-9999	-10000	0	0
ODF2	0	0	-9999	-10000	0	0
BUB1	0.023	0.016	-9999	-10000	0	0
TPT1	0.001	0.013	-9999	-10000	0	0
CDC25C	-0.007	0.015	-9999	-10000	0	0
CDC25B	-0.001	0.041	-9999	-0.29	20	20
SGOL1	-0.028	0.03	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.022	0.042	-9999	-10000	0	0
CDC14B	-0.009	0.11	-9999	-0.63	32	32
CDC20	-0.16	0.14	-9999	-0.29	563	563
PLK1/PBIP1	-0.029	0.054	-9999	-0.18	4	4
mitosis	-0.006	0.007	-9999	-0.022	2	2
FBXO5	0	0.022	-9999	-0.15	1	1
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.14	-9999	-0.29	634	634
metaphase plate congression	-0.002	0.015	-9999	-10000	0	0
ERCC6L	-0.064	0.089	-9999	-10000	0	0
NLP/gamma Tubulin	0	0.013	-9999	-10000	0	0
microtubule cytoskeleton organization	0.001	0.013	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.14	0.1	-9999	-0.28	267	267
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.003	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.002	0.023	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.05	-9999	-0.3	26	26
microtubule-based process	-0.11	0.068	-9999	-0.17	213	213
Golgi organization	-0.008	0.023	-9999	-10000	0	0
Cohesin/SA2	-0.01	0.018	-9999	-0.46	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-0.29	777	777
APC/C/CDC20	-0.087	0.079	-9999	-0.17	418	418
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.029	0.053	-9999	-0.18	4	4
PRC1	-0.075	0.13	-9999	-0.29	268	268
ECT2	-0.004	0.039	-9999	-0.19	5	5
C13orf34	0	0.021	-9999	-10000	0	0
NUDC	-0.002	0.015	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.038	0.051	-9999	-10000	0	0
spindle assembly	-0.003	0.019	-9999	-10000	0	0
spindle stabilization	0.001	0.013	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.094	-9999	-0.54	32	32
MKLP2/PLK1	-0.12	0.068	-9999	-0.17	213	213
CCNB1	-0.057	0.12	-9999	-0.29	215	215
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	-0.008	0.086	-9999	-0.52	28	28
TUBG1	0.001	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.04	-9999	-10000	0	0
MLF1IP	-0.027	0.075	-9999	-0.2	78	78
INCENP	0	0.002	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.008	0.056	-9999	-0.46	15	15
RGS9BP	-0.019	0.072	-9999	-0.29	68	68
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.028	-9999	-0.29	10	10
mol:Na +	-0.02	0.052	-9999	-10000	0	0
mol:ADP	0.008	0.026	-9999	-10000	0	0
GNAT2	-0.001	0.018	-9999	-0.29	4	4
RGS9-1/Gbeta5/R9AP	-0.064	0.16	-9999	-0.54	104	104
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.015	-9999	-10000	0	0
GRK7	-0.002	0.024	-9999	-0.29	7	7
CNGB3	-0.011	0.054	-9999	-0.29	38	38
Cone Metarhodopsin II/X-Arrestin	-0.002	0.017	-9999	-10000	0	0
mol:Ca2+	-0.095	0.084	-9999	-0.28	82	82
Cone PDE6	-0.056	0.14	-9999	-0.47	104	104
Cone Metarhodopsin II	-0.002	0.018	-9999	-10000	0	0
Na + (4 Units)	-0.098	0.08	-9999	-0.27	82	82
GNAT2/GDP	-0.055	0.14	-9999	-0.47	104	104
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.007	0.016	-9999	-10000	0	0
Cone Transducin	-0.008	0.059	-9999	-0.49	15	15
SLC24A2	-0.18	0.14	-9999	-0.29	631	631
GNB3/GNGT2	-0.009	0.074	-9999	-0.61	15	15
GNB3	-0.011	0.091	-9999	-0.71	16	16
GNAT2/GTP	-0.001	0.012	-9999	-10000	0	0
CNGA3	-0.027	0.084	-9999	-0.29	96	96
ARR3	-0.002	0.025	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.02	0.052	-9999	-10000	0	0
mol:Pi	-0.064	0.16	-9999	-0.54	104	104
Cone CNG Channel	-0.016	0.039	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.18	0.14	-9999	-0.29	631	631
RGS9	-0.084	0.24	-9999	-0.74	118	118
PDE6C	0	0.009	-9999	-0.29	1	1
GNGT2	-0.002	0.035	-9999	-0.8	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.002	0.022	-9999	-0.29	6	6

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.002	0.035	-9999	-0.8	2	2
LAT2	-0.062	0.14	-9999	-0.43	86	86
AP1	-0.15	0.22	-9999	-0.44	328	328
mol:PIP3	-0.027	0.2	-9999	-0.51	89	89
IKBKB	0.002	0.12	-9999	-0.32	49	49
AKT1	-0.082	0.17	-9999	-0.67	43	43
IKBKG	0.002	0.12	-9999	-0.32	49	49
MS4A2	-0.067	0.22	-9999	-0.78	89	89
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
MAP3K1	0.006	0.13	-9999	-0.44	41	41
mol:Ca2+	-0.012	0.15	-9999	-0.37	89	89
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.061	0.14	-9999	-0.43	86	86
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.063	0.16	-9999	-0.49	133	133
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.097	0.21	-9999	-0.49	203	203
PTPN13	-0.031	0.17	-9999	-0.54	64	64
PTPN11	0.01	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.007	0.15	-9999	-0.42	40	40
SYK	0.011	0.01	-9999	-0.29	1	1
GRB2	0	0.009	-9999	-0.29	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.086	0.18	-9999	-0.52	89	89
LAT	-0.063	0.14	-9999	-0.43	87	87
PAK2	-0.003	0.14	-9999	-0.49	41	41
NFATC2	-0.1	0.24	-9999	-0.82	93	93
HRAS	-0.012	0.15	-9999	-0.53	43	43
GAB2	-0.004	0.044	-9999	-0.38	11	11
PLA2G1B	0.028	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.25	-9999	-0.61	203	203
Antigen/IgE/Fc epsilon R1	-0.11	0.24	-9999	-0.56	203	203
mol:GDP	-0.019	0.15	-9999	-0.55	43	43
JUN	-0.005	0.066	-9999	-0.8	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.81	10	10
FOS	-0.24	0.37	-9999	-0.8	307	307
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.066	0.15	-9999	-0.45	88	88
CHUK	0.002	0.12	-9999	-0.32	49	49
KLRG1	-0.061	0.13	-9999	-0.5	48	48
VAV1	-0.063	0.14	-9999	-0.44	89	89
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.061	0.14	-9999	-0.43	86	86
negative regulation of mast cell degranulation	-0.056	0.12	-9999	-0.51	39	39
BTK	-0.06	0.14	-9999	-0.43	87	87
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.085	0.2	-9999	-0.43	205	205
GAB2/PI3K/SHP2	-0.091	0.19	-9999	-0.74	45	45
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.069	0.16	-9999	-0.68	40	40
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.52	205	205
FCER1G	0.003	0.012	-9999	-0.29	1	1
FCER1A	-0.11	0.29	-9999	-0.81	153	153
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.22	-9999	-0.53	203	203
MAPK3	0.026	0.019	-9999	-10000	0	0
MAPK1	0.026	0.019	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.01	0.079	-9999	-0.67	9	9
DUSP1	-0.1	0.27	-9999	-0.8	133	133
NF-kappa-B/RelA	-0.027	0.054	-9999	-0.24	1	1
actin cytoskeleton reorganization	-0.026	0.15	-9999	-0.56	37	37
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.057	0.13	-9999	-0.52	48	48
FER	-0.066	0.15	-9999	-0.45	93	93
RELA	0	0	-9999	-10000	0	0
ITK	-0.036	0.12	-9999	-0.6	39	39
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.016	0.16	-9999	-0.57	42	42
cytokine secretion	-0.019	0.04	-9999	-10000	0	0
SPHK1	-0.064	0.14	-9999	-0.44	89	89
PTK2	-0.028	0.16	-9999	-0.58	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.089	0.19	-9999	-0.55	89	89
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.022	0.2	-9999	-0.49	90	90
MAP2K2	0.022	0.019	-9999	-10000	0	0
MAP2K1	0.022	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.12	-9999	-0.51	39	39
MAP2K4	0.016	0.034	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.11	0.24	-9999	-0.56	205	205
mol:Choline	-0.095	0.2	-9999	-0.48	203	203
SHC/Grb2/SOS1	-0.055	0.13	-9999	-0.53	37	37
FYN	-0.002	0.035	-9999	-0.8	2	2
DOK1	-0.001	0.018	-9999	-0.29	4	4
PXN	-0.018	0.15	-9999	-0.53	37	37
HCLS1	-0.061	0.14	-9999	-0.43	86	86
PRKCB	-0.014	0.16	-9999	-0.39	94	94
FCGR2B	-0.003	0.051	-9999	-0.8	4	4
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.057	0.12	-9999	-0.52	39	39
LCP2	0	0.009	-9999	-0.29	1	1
PLA2G4A	-0.11	0.21	-9999	-0.51	186	186
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.095	0.2	-9999	-0.48	203	203
IKK complex	0.02	0.093	-9999	-0.23	45	45
WIPF1	0	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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
PDGFRB	-0.003	0.05	-9999	-0.8	4	4
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.61	35	35
PTK2	-0.065	0.19	-9999	-0.58	112	112
positive regulation of JNK cascade	-0.037	0.11	-9999	-0.34	112	112
CDC42/GDP	-0.001	0.16	-9999	-0.46	112	112
Rac1/GDP	0.002	0.16	-9999	-0.46	112	112
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.046	0.13	-9999	-0.42	112	112
nectin-3/I-afadin	-0.069	0.2	-9999	-0.64	112	112
RAPGEF1	-0.009	0.18	-9999	-0.53	112	112
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.023	0.21	-9999	-0.62	112	112
PDGFB-D/PDGFRB	-0.003	0.05	-9999	-0.8	4	4
TLN1	0.001	0.1	-9999	-0.53	14	14
Rap1/GTP	-0.04	0.11	-9999	-0.36	112	112
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.037	-9999	-0.49	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.64	112	112
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.012	0.2	-9999	-0.58	112	112
MLLT4	-0.005	0.062	-9999	-0.73	7	7
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.057	0.17	-9999	-0.5	117	117
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.047	-9999	-0.61	6	6
positive regulation of lamellipodium assembly	-0.039	0.11	-9999	-0.36	112	112
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.086	0.25	-9999	-0.8	111	111
PVRL2	-0.001	0.016	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
CDH1	-0.025	0.14	-9999	-0.8	32	32
CLDN1	-0.036	0.15	-9999	-0.58	64	64
JAM-A/CLDN1	-0.074	0.19	-9999	-0.52	140	140
SRC	-0.077	0.22	-9999	-0.7	112	112
ITGB3	-0.028	0.15	-9999	-0.75	39	39
nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.047	-9999	-0.61	6	6
FARP2	-0.017	0.2	-9999	-0.57	112	112
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.06	0.17	-9999	-0.55	112	112
nectin-1/I-afadin	-0.004	0.047	-9999	-0.61	6	6
nectin-2/I-afadin	-0.004	0.048	-9999	-0.61	6	6
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	-0.06	0.17	-9999	-0.55	112	112
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.037	0.11	-9999	-0.34	112	112
alphaV/beta3 Integrin/Talin	-0.04	0.13	-9999	-0.6	40	40
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-9999	-0.61	6	6
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.048	-9999	-0.61	6	6
PIP5K1C	-0.032	0.1	-9999	-0.29	116	116
VAV2	-0.018	0.2	-9999	-0.58	112	112
RAP1/GDP	-0.047	0.13	-9999	-0.43	112	112
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.06	0.17	-9999	-0.55	112	112
nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.64	112	112
Rac1/GTP	-0.048	0.14	-9999	-0.44	112	112
PTPRM	-0.037	0.11	-9999	-0.33	116	116
E-cadherin/beta catenin/alpha catenin	-0.016	0.082	-9999	-0.44	37	37
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.009	0.049	-10000	0	-0.43	10	10
adherens junction organization	0.03	0.067	-10000	0	-0.31	33	33
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.18	-10000	0	-0.38	385	385
FMN1	0.022	0.094	-10000	0	-0.46	23	23
mol:IP3	-0.009	0.048	-10000	0	-0.4	10	10
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.057	-10000	0	-0.32	33	33
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.01	0.05	-10000	0	-0.39	10	10
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.088	-10000	0	-0.51	32	32
CTNND1	0.011	0.01	-10000	0	-0.28	1	1
mol:PI-4-5-P2	0.032	0.06	-10000	0	-10000	0	0
VASP	0.032	0.061	-10000	0	-10000	0	0
ZYX	0.032	0.061	-10000	0	-10000	0	0
JUB	0.03	0.067	-10000	0	-0.42	4	4
EGFR(dimer)	-0.16	0.21	-10000	0	-0.43	393	393
E-cadherin/beta catenin-gamma catenin	-0.016	0.09	-10000	0	-0.51	33	33
mol:PI-3-4-5-P3	-0.01	0.054	-10000	0	-0.42	10	10
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PI3K	-0.011	0.055	-10000	0	-0.42	10	10
FYN	0.04	0.054	-10000	0	-0.38	2	2
mol:Ca2+	-0.009	0.047	-10000	0	-0.39	10	10
JUP	0	0.027	-10000	0	-0.55	2	2
PIK3R1	-0.008	0.078	-10000	0	-0.8	10	10
mol:DAG	-0.009	0.048	-10000	0	-0.4	10	10
CDH1	-0.025	0.14	-10000	0	-0.8	32	32
RhoA/GDP	-0.14	0.18	-10000	0	-0.57	21	21
establishment of polarity of embryonic epithelium	0.032	0.06	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.29	0.39	-10000	0	-0.8	383	383
CASR	0.008	0.054	-10000	0	-0.37	10	10
RhoA/GTP	-0.008	0.042	-10000	0	-10000	0	0
AKT2	-0.01	0.05	-10000	0	-0.39	10	10
actin cable formation	0.029	0.091	-10000	0	-0.44	22	22
apoptosis	0.01	0.05	0.4	10	-10000	0	10
CTNNA1	0.011	0.002	-10000	0	-10000	0	0
mol:GDP	-0.16	0.2	-10000	0	-0.41	385	385
PIP5K1A	0.032	0.061	-10000	0	-10000	0	0
PLCG1	-0.009	0.049	-10000	0	-0.41	10	10
Rac1/GTP	-0.15	0.19	-10000	0	-0.4	379	379
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.005	0.052	-10000	0	-0.54	9	9
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.004	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.068	0.22	-10000	0	-0.8	88	88
LRP6/FZD1	0	0.008	-10000	0	-10000	0	0
TLE1	-0.005	0.07	-10000	0	-0.8	8	8
AP1	-0.11	0.18	-10000	0	-0.37	311	311
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.002	0.043	-10000	0	-0.8	3	3
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.045	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.002	0.038	-10000	0	-0.71	3	3
WIF1	-0.42	0.4	-10000	0	-0.79	554	554
NOTCH1	-0.002	0.041	-10000	0	-0.76	3	3
PSENEN	0	0.009	-10000	0	-0.29	1	1
KREMEN2	-0.14	0.14	-10000	0	-0.29	500	500
DKK1	-0.079	0.19	-10000	0	-0.42	194	194
beta catenin/beta TrCP1	-0.009	0.025	-10000	0	-10000	0	0
APH1B	-0.001	0.025	-10000	0	-0.8	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.014	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.003	0.04	-10000	0	-0.34	8	8
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.37	-10000	0	-0.8	307	307
JUN	-0.005	0.066	-10000	0	-0.8	7	7
MAP3K7	0.001	0.01	-10000	0	-0.29	1	1
CTNNB1	-0.003	0.035	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.083	0.11	-10000	0	-0.61	28	28
HNF1A	-0.001	0.024	-10000	0	-0.29	7	7
CTBP1	0.001	0.004	-10000	0	-10000	0	0
MYC	-0.033	0.22	-10000	0	-1.5	23	23
NKD1	-0.009	0.07	-10000	0	-0.43	22	22
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.04	0.13	-10000	0	-0.45	91	91
apoptosis	-0.11	0.17	-10000	0	-0.37	311	311
Delta 1/NOTCHprecursor	-0.005	0.051	-10000	0	-0.53	9	9
DLL1	-0.005	0.061	-10000	0	-0.8	6	6
PPARD	-0.001	0.012	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.014	-10000	0	-0.45	1	1
APC	0.003	0.014	-10000	0	-10000	0	0
DVL1	-0.038	0.036	-10000	0	-10000	0	0
CSNK2A1	0	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.58	53	53
LRP6	-0.001	0.013	-10000	0	-0.29	2	2
CSNK1A1	0	0.001	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.012	0.096	-10000	0	-1.5	4	4
WNT1	-0.001	0.013	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.01	0.037	-10000	0	-10000	0	0
DKK2	-0.022	0.13	-10000	0	-0.77	30	30
NOTCH1 precursor/DVL1	-0.019	0.039	-10000	0	-0.66	3	3
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	0.001	0.004	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.04	0.13	-10000	0	-0.45	91	91
PPP2R5D	-0.015	0.038	0.36	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.25	0.24	-10000	0	-0.48	540	540
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.55	0.37	-9999	-0.8	709	709
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.007	0.044	-9999	-0.29	25	25
TCEB1	-0.001	0.013	-9999	-0.29	2	2
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.007	-9999	-10000	0	0
COPS5	0	0.009	-9999	-0.29	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.016	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.05	0.11	-9999	-0.29	179	179
ARNT/IPAS	-0.42	0.29	-9999	-0.61	709	709
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0.009	-9999	-0.29	1	1
RACK1/Elongin B/Elongin C	-0.004	0.022	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.038	-9999	-0.48	2	2
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.014	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
HIF1A/JAB1	-0.001	0.007	-9999	-10000	0	0
EGLN3	-0.022	0.08	-9999	-0.3	78	78
EGLN2	-0.002	0.022	-9999	-0.29	6	6
EGLN1	-0.001	0.025	-9999	-0.8	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.001	0.005	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.019	0.039	-9999	-10000	0	0

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.11	0.21	-10000	0	-0.48	247	247
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.021	-10000	0	-10000	0	0
GNB1/GNG2	-0.006	0.058	-10000	0	-0.54	12	12
GNB1	0	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	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.21	-10000	0	-0.5	244	244
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	0.027	0.048	0.11	244	-10000	0	244
GNAL	-0.19	0.34	-10000	0	-0.8	244	244
GNG2	-0.009	0.086	-10000	0	-0.8	12	12
CRH	-0.003	0.03	-10000	0	-0.29	11	11
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.04	-10000	0	-0.45	8	8
MAPK11	0.007	0.025	-10000	0	-0.45	3	3

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.01	0.058	-10000	0	-0.33	33	33
epithelial cell differentiation	-0.014	0.078	-10000	0	-0.45	32	32
CYFIP2	-0.01	0.067	-10000	0	-0.36	30	30
ENAH	0.056	0.063	-10000	0	-10000	0	0
EGFR	-0.29	0.39	-10000	0	-0.8	383	383
EPHA2	-0.005	0.061	-10000	0	-0.8	6	6
MYO6	-0.014	0.075	-10000	0	-0.43	33	33
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.006	0.039	-10000	0	-0.53	4	4
AQP5	-0.24	0.3	-10000	0	-0.6	412	412
CTNND1	0	0.009	-10000	0	-0.29	1	1
mol:PI-4-5-P2	-0.013	0.073	-10000	0	-0.42	32	32
regulation of calcium-dependent cell-cell adhesion	-0.036	0.12	-10000	0	-0.43	86	86
EGF	-0.16	0.32	-10000	0	-0.8	202	202
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.039	0.14	-10000	0	-0.57	56	56
cortical microtubule organization	-0.014	0.078	-10000	0	-0.45	32	32
GO:0000145	0.024	0.076	-10000	0	-0.4	32	32
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.014	0.079	-10000	0	-0.46	32	32
MLLT4	-0.005	0.062	-10000	0	-0.73	7	7
ARF6/GDP	-0.013	0.066	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.037	-10000	0	-0.48	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.035	0.08	-10000	0	-0.39	32	32
PVRL2	-0.001	0.016	-10000	0	-10000	0	0
ZYX	-0.013	0.074	-10000	0	-0.43	32	32
ARF6/GTP	-0.003	0.034	-10000	0	-0.44	6	6
CDH1	-0.025	0.14	-10000	0	-0.8	32	32
EGFR/EGFR/EGF/EGF	-0.24	0.26	-10000	0	-0.47	533	533
RhoA/GDP	-0.013	0.073	-10000	0	-0.42	32	32
actin cytoskeleton organization	0.031	0.079	-10000	0	-0.4	33	33
IGF-1R heterotetramer	-0.021	0.12	-10000	0	-0.8	22	22
GIT1	-0.001	0.02	-10000	0	-10000	0	0
IGF1R	-0.021	0.12	-10000	0	-0.8	22	22
IGF1	-0.18	0.33	-10000	0	-0.8	231	231
DIAPH1	-0.002	0.045	-10000	0	-0.7	4	4
Wnt receptor signaling pathway	0.014	0.078	0.45	32	-10000	0	32
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.013	0.066	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	0.031	0.08	-10000	0	-0.41	33	33
EFNA1	0	0	-10000	0	-10000	0	0
LPP	0.028	0.087	-10000	0	-0.4	40	40
Ephrin A1/EPHA2	-0.015	0.077	-10000	0	-0.41	38	38
SEC6/SEC8	-0.014	0.072	-10000	0	-0.76	1	1
MGAT3	-0.037	0.12	-10000	0	-0.44	86	86
HGF/MET	-0.11	0.21	-10000	0	-0.46	244	244
HGF	-0.053	0.2	-10000	0	-0.8	68	68
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.011	0.058	-10000	0	-0.33	33	33
actin cable formation	0.07	0.061	-10000	0	-0.33	1	1
KIAA1543	0.03	0.089	-10000	0	-0.44	33	33
KIFC3	-0.014	0.076	-10000	0	-0.43	34	34
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.014	0.075	-10000	0	-0.43	33	33
NCK1/GIT1	-0.001	0.013	-10000	0	-10000	0	0
mol:GDP	-0.014	0.078	-10000	0	-0.45	32	32
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.013	0.074	-10000	0	-0.43	32	32
PIP5K1C	-0.013	0.074	-10000	0	-0.43	32	32
LIMA1	-0.001	0.025	-10000	0	-0.8	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.012	0.059	-10000	0	-10000	0	0
adherens junction assembly	0.046	0.086	-10000	0	-0.64	4	4
IGF-1R heterotetramer/IGF1	-0.12	0.2	-10000	0	-0.44	267	267
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-10000	0	-0.61	6	6
MET	-0.13	0.3	-10000	0	-0.8	172	172
PLEKHA7	-0.014	0.081	-10000	0	-0.46	32	32
mol:GTP	-0.003	0.037	-10000	0	-0.48	6	6
establishment of epithelial cell apical/basal polarity	-0.013	0.068	-10000	0	-0.72	1	1
cortical actin cytoskeleton stabilization	-0.01	0.058	-10000	0	-0.33	33	33
regulation of cell-cell adhesion	0.031	0.079	-10000	0	-0.4	33	33
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.011	0.058	-10000	0	-0.33	33	33

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.025	-10000	0	-0.8	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.077	0.62	1	-10000	0	1
CDKN1A	-0.002	0.042	-10000	0	-0.95	2	2
KAT2B	-0.001	0.025	-10000	0	-0.8	1	1
BAX	-0.001	0.02	-10000	0	-0.29	5	5
FOXO3	-0.001	0.018	-10000	0	-0.33	3	3
FOXO1	-0.008	0.079	-10000	0	-0.8	10	10
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.57	0.36	-10000	0	-0.79	753	753
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.03	-10000	0	-0.61	1	1
PPARGC1A	-0.17	0.33	-10000	0	-0.78	229	229
FHL2	-0.005	0.061	-10000	0	-0.8	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.012	0.077	-10000	0	-0.62	1	1
SIRT1/FOXO3a	0	0.015	-10000	0	-0.25	3	3
SIRT1	0	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.018	-10000	0	-0.53	1	1
SIRT1/Histone H1b	-0.003	0.012	-10000	0	-10000	0	0
apoptosis	0	0.012	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.12	0.22	-10000	0	-0.54	218	218
p53/SIRT1	0.001	0.019	0.43	2	-10000	0	2
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.061	-10000	0	-0.49	16	16
HIST1H1E	-0.005	0.015	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.024	0.53	1	-10000	0	1
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.012	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.44	0.28	-10000	0	-0.62	727	727
ACSS2	0.019	0.02	-10000	0	-0.62	1	1
SIRT1/PCAF/MYOD	-0.002	0.024	-10000	0	-0.53	1	1

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.011	0.053	0.29	36	-10000	0	36
RFC1	0.011	0.053	0.29	36	-10000	0	36
PRKDC	0.01	0.054	0.29	36	-10000	0	36
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.023	0.037	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.016	0.067	0.25	17	-0.38	15	32
MAP2K4	-0.058	0.16	-10000	0	-0.42	30	30
mol:ceramide	-0.031	0.11	-10000	0	-0.54	19	19
GSN	0.004	0.077	0.29	35	-0.5	13	48
FASLG/FAS/FADD/FAF1/Caspase 8	-0.03	0.071	0.23	14	-0.46	15	29
FAS	0.004	0.051	-10000	0	-0.81	4	4
BID	0.001	0.011	0.32	1	-10000	0	1
MAP3K1	-0.021	0.093	-10000	0	-0.29	14	14
MAP3K7	0	0.009	-10000	0	-0.29	1	1
RB1	0.01	0.053	0.29	35	-0.3	1	36
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.27	-10000	0	-0.6	236	236
ARHGDIB	0.01	0.054	0.29	36	-10000	0	36
FADD	0.003	0.038	-10000	0	-0.3	15	15
actin filament polymerization	-0.004	0.077	0.5	13	-0.29	35	48
NFKB1	-0.076	0.1	-10000	0	-0.32	2	2
MAPK8	-0.12	0.24	-10000	0	-0.43	385	385
DFFA	0.011	0.053	0.29	36	-10000	0	36
DNA fragmentation during apoptosis	0.011	0.053	0.29	36	-10000	0	36
FAS/FADD/MET	-0.094	0.21	-10000	0	-0.56	173	173
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.052	-10000	0	-0.31	26	26
FAF1	0.008	0.006	-10000	0	-10000	0	0
PARP1	0.011	0.053	0.29	36	-10000	0	36
DFFB	0.011	0.053	0.29	36	-10000	0	36
CHUK	-0.066	0.088	-10000	0	-10000	0	0
FASLG	-0.015	0.11	-10000	0	-0.42	54	54
FAS/FADD	-0.005	0.048	-10000	0	-0.67	4	4
HGF	-0.053	0.2	-10000	0	-0.8	68	68
LMNA	0.01	0.048	0.26	36	-10000	0	36
CASP6	0.011	0.053	0.29	36	-10000	0	36
CASP10	0.004	0.051	-10000	0	-0.81	4	4
CASP3	0.013	0.064	0.34	37	-10000	0	37
PTPN13	-0.025	0.14	-10000	0	-0.8	32	32
CASP8	0.003	0.02	0.45	1	-10000	0	1
IL6	-0.47	0.67	-10000	0	-1.4	380	380
MET	-0.13	0.3	-10000	0	-0.8	172	172
ICAD/CAD	0.01	0.049	0.26	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 10	-0.032	0.12	-10000	0	-0.55	19	19
activation of caspase activity by cytochrome c	0.001	0.011	0.32	1	-10000	0	1
PAK2	0.011	0.052	0.28	36	-10000	0	36
BCL2	-0.023	0.15	-10000	0	-0.8	36	36

×

LPA4-mediated signaling events

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
ADCY4	0	0.1	-9999	-0.54	38	38
ADCY5	-0.16	0.26	-9999	-0.54	339	339
ADCY6	0.02	0	-9999	-10000	0	0
ADCY7	0.02	0	-9999	-10000	0	0
ADCY1	-0.007	0.097	-9999	-0.54	26	26
ADCY2	-0.029	0.15	-9999	-0.54	80	80
ADCY3	0.02	0.005	-9999	-10000	0	0
ADCY8	0.009	0.028	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.031	0.1	-9999	-0.31	69	69

×

TCGA08_rtk_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
PDGFRA	-0.05	0.19	-10000	0	-0.8	65	65
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
EGFR	-0.29	0.39	-10000	0	-0.8	383	383
AKT	0.014	0.079	-10000	0	-0.56	17	17
FOXO3	-0.002	0.043	-10000	0	-0.8	3	3
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.008	0.079	-10000	0	-0.8	10	10
AKT3	-0.013	0.1	-10000	0	-0.8	17	17
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.13	0.3	-10000	0	-0.8	172	172
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
PIK3CG	-0.014	0.1	-10000	0	-0.7	20	20
PIK3R3	0	0.009	-10000	0	-0.29	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.025	-10000	0	-0.8	1	1
RAS	-0.093	0.16	0.26	1	-0.37	194	195
ERBB2	-0.023	0.078	-10000	0	-0.29	82	82
proliferation/survival/translation	-0.005	0.057	0.27	12	-10000	0	12
PI3K	-0.084	0.16	-10000	0	-0.36	201	201
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
FOXO	0.027	0.029	-10000	0	-0.5	1	1
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.035	-10000	0	-0.8	2	2

×

Signaling events mediated by PRL

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
CCNE1	-0.059	0.12	-9999	-0.29	210	210
mol:Halofuginone	0	0.003	-9999	-10000	0	0
ITGA1	-0.008	0.079	-9999	-0.8	10	10
CDKN1A	-0.058	0.09	-9999	-0.85	2	2
PRL-3/alpha Tubulin	-0.002	0.018	-9999	-10000	0	0
mol:Ca2+	-0.035	0.098	-9999	-0.56	17	17
AGT	-0.049	0.13	-9999	-0.34	152	152
CCNA2	-0.16	0.24	-9999	-0.56	176	176
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.18	0.29	-9999	-0.61	328	328
CDK2/Cyclin E1	-0.068	0.091	-9999	-0.82	2	2
MAPK3	0.02	0.02	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.008	-9999	-10000	0	0
MAPK1	0.02	0.02	-9999	-10000	0	0
PTP4A1	-0.12	0.24	-9999	-0.47	328	328
PTP4A3	-0.003	0.028	-9999	-0.29	10	10
PTP4A2	-0.001	0.013	-9999	-0.29	2	2
ITGB1	0.02	0.02	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
RAC1	-0.056	0.083	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.14	0.2	-9999	-0.6	2	2
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.009	-9999	-10000	0	0
RHOC	-0.056	0.083	-9999	-10000	0	0
RHOA	-0.056	0.083	-9999	-10000	0	0
cell motility	-0.035	0.1	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.14	0.2	-9999	-0.63	1	1
PRL-3/alpha1 Integrin	-0.008	0.062	-9999	-0.61	10	10
ROCK1	-0.035	0.11	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.12	0.24	-9999	-0.47	328	328
ATF5	-0.001	0.018	-9999	-0.29	4	4

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.047	-9999	-0.63	5	5
PDGFRB	0.004	0.051	-9999	-0.81	4	4
SPHK1	-0.025	0.056	-9999	-1.1	2	2
mol:S1P	-0.031	0.058	-9999	-0.97	2	2
S1P1/S1P/Gi	-0.099	0.23	-9999	-0.6	85	85
GNAO1	-0.024	0.14	-9999	-0.49	66	66
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.6	65	65
PLCG1	-0.088	0.22	-9999	-0.63	64	64
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.051	-9999	-0.81	4	4
GNAI2	0.008	0.006	-9999	-10000	0	0
GNAI3	0.008	0.006	-9999	-10000	0	0
GNAI1	-0.032	0.18	-9999	-0.82	50	50
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.045	-9999	-0.55	5	5
S1P1/S1P	-0.045	0.075	-9999	-0.62	7	7
negative regulation of cAMP metabolic process	-0.096	0.22	-9999	-0.58	85	85
MAPK3	-0.16	0.31	-9999	-0.57	351	351
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.004	0.056	-9999	-0.81	5	5
PLCB2	-0.008	0.086	-9999	-0.53	8	8
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.061	-9999	-0.5	7	7
receptor internalization	-0.042	0.07	-9999	-0.57	7	7
PTGS2	-0.33	0.55	-9999	-1.1	350	350
Rac1/GTP	-0.037	0.061	-9999	-0.5	7	7
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.03	-9999	-0.3	1	1
negative regulation of T cell proliferation	-0.096	0.22	-9999	-0.58	85	85
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.001	0.076	-9999	-0.81	9	9
MAPK1	-0.16	0.31	-9999	-0.57	351	351
S1P1/S1P/PDGFB-D/PDGFRB	-0.02	0.11	-9999	-0.68	9	9
ABCC1	0	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.002	0.011	-10000	0	-0.29	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.033	0.13	0.42	42	-10000	0	42
IL27/IL27R/JAK1	-0.071	0.18	-10000	0	-0.65	48	48
TBX21	-0.043	0.22	-10000	0	-0.64	67	67
IL12B	-0.054	0.12	-10000	0	-0.29	214	214
IL12A	-0.03	0.15	-10000	0	-0.57	68	68
IL6ST	-0.088	0.27	-10000	0	-0.81	124	124
IL27RA/JAK1	-0.007	0.063	-10000	0	-1.1	3	3
IL27	-0.023	0.092	-10000	0	-10000	0	0
TYK2	0.01	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.13	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.033	0.13	0.42	42	-10000	0	42
T cell proliferation during immune response	0.033	0.13	0.42	42	-10000	0	42
MAPKKK cascade	-0.033	0.13	-10000	0	-0.42	42	42
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.04	-10000	0	-0.29	19	19
IL12RB1	-0.013	0.066	-10000	0	-0.32	42	42
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.058	0.23	-10000	0	-0.62	98	98
IL27/IL27R/JAK2/TYK2	-0.033	0.13	-10000	0	-0.42	42	42
positive regulation of T cell mediated cytotoxicity	-0.033	0.13	-10000	0	-0.42	42	42
STAT1 (dimer)	-0.092	0.23	0.47	19	-0.74	55	74
JAK2	0.004	0.026	-10000	0	-0.81	1	1
JAK1	0	0.025	-10000	0	-0.8	1	1
STAT2 (dimer)	-0.044	0.11	-10000	0	-0.43	26	26
T cell proliferation	-0.19	0.25	-10000	0	-0.47	398	398
IL12/IL12R/TYK2/JAK2	0.011	0.072	-10000	0	-10000	0	0
IL17A	-0.13	0.18	-10000	0	-10000	0	0
mast cell activation	0.033	0.13	0.42	42	-10000	0	42
IFNG	0	0.025	-10000	0	-0.084	3	3
T cell differentiation	-0.004	0.006	-10000	0	-0.019	21	21
STAT3 (dimer)	-0.044	0.11	-10000	0	-0.45	22	22
STAT5A (dimer)	-0.047	0.12	-10000	0	-0.46	32	32
STAT4 (dimer)	-0.062	0.14	-10000	0	-0.5	63	63
STAT4	-0.032	0.16	-10000	0	-0.79	42	42
T cell activation	-0.009	0.008	0.13	2	-10000	0	2
IL27R/JAK2/TYK2	-0.06	0.16	-10000	0	-0.52	73	73
GATA3	-0.039	0.27	-10000	0	-1.5	37	37
IL18	0.006	0.032	-10000	0	-0.2	8	8
positive regulation of mast cell cytokine production	-0.043	0.11	-10000	0	-0.44	22	22
IL27/EBI3	-0.025	0.083	-10000	0	-0.54	13	13
IL27RA	0	0.067	-10000	0	-1.4	2	2
IL6	-0.29	0.39	-10000	0	-0.8	380	380
STAT5A	-0.006	0.07	-10000	0	-0.8	8	8
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.004	0.026	0.48	2	-10000	0	2
IL1B	0.001	0.077	-10000	0	-0.53	19	19
EBI3	-0.004	0.077	-10000	0	-0.52	18	18
TNF	-0.002	0.079	-10000	0	-0.62	14	14

×

Syndecan-4-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.001	0.035	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.023	0.035	-9999	-0.64	1	1
positive regulation of JNK cascade	-0.049	0.11	-9999	-0.42	35	35
Syndecan-4/ADAM12	-0.031	0.053	-9999	-0.55	2	2
CCL5	-0.015	0.081	-9999	-0.36	44	44
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.001	0.021	-9999	-0.29	5	5
ADAM12	-0.019	0.077	-9999	-0.3	65	65
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.002	0.022	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.054	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.073	0.14	-9999	-0.47	62	62
Syndecan-4/CXCL12/CXCR4	-0.051	0.11	-9999	-0.46	19	19
Syndecan-4/Laminin alpha3	-0.13	0.2	-9999	-0.49	190	190
MDK	-0.011	0.056	-9999	-0.29	41	41
Syndecan-4/FZD7	-0.031	0.067	-9999	-0.47	13	13
Syndecan-4/Midkine	-0.027	0.04	-9999	-0.64	1	1
FZD7	-0.015	0.11	-9999	-0.8	20	20
Syndecan-4/FGFR1/FGF	-0.19	0.21	-9999	-0.49	155	155
THBS1	-0.003	0.05	-9999	-0.8	4	4
integrin-mediated signaling pathway	-0.033	0.073	-9999	-0.47	16	16
positive regulation of MAPKKK cascade	-0.049	0.11	-9999	-0.42	35	35
Syndecan-4/TACI	-0.034	0.066	-9999	-0.5	7	7
CXCR4	-0.007	0.045	-9999	-10000	0	0
cell adhesion	-0.02	0.062	-9999	-0.34	27	27
Syndecan-4/Dynamin	-0.022	0.034	-9999	-0.64	1	1
Syndecan-4/TSP1	-0.024	0.043	-9999	-0.5	4	4
Syndecan-4/GIPC	-0.023	0.035	-9999	-0.64	1	1
Syndecan-4/RANTES	-0.03	0.052	-9999	-0.49	6	6
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.094	0.26	-9999	-0.79	123	123
LAMA3	-0.2	0.35	-9999	-0.8	259	259
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.003	0.13	-9999	-0.73	29	29
Syndecan-4/alpha-Actinin	-0.023	0.037	-9999	-0.55	2	2
TFPI	-0.037	0.17	-9999	-0.8	48	48
F2	0.001	0.029	-9999	-0.29	10	10
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.24	-9999	-0.53	200	200
ACTN1	-0.001	0.025	-9999	-0.8	1	1
TNC	-0.021	0.12	-9999	-0.8	24	24
Syndecan-4/CXCL12	-0.056	0.11	-9999	-0.46	37	37
FGF6	-0.002	0.035	-9999	-0.8	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.062	0.21	-9999	-0.8	80	80
TNFRSF13B	-0.026	0.11	-9999	-0.8	15	15
FGF2	-0.32	0.39	-9999	-0.8	416	416
FGFR1	-0.009	0.084	-9999	-0.69	14	14
Syndecan-4/PI-4-5-P2	-0.016	0.047	-9999	-0.65	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.15	-9999	-0.3	413	413
cell migration	-0.024	0.019	-9999	-10000	0	0
PRKCD	0.005	0.014	-9999	-0.28	1	1
vasculogenesis	-0.024	0.042	-9999	-0.46	5	5
SDC4	-0.016	0.05	-9999	-0.69	1	1
Syndecan-4/Tenascin C	-0.033	0.075	-9999	-0.49	16	16
Syndecan-4/PI-4-5-P2/PKC alpha	-0.043	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.022	0.034	-9999	-0.64	1	1
MMP9	-0.12	0.15	-9999	-0.29	453	453
Rac1/GTP	-0.028	0.058	-9999	-0.35	27	27
cytoskeleton organization	-0.023	0.034	-9999	-0.61	1	1
GIPC1	-0.001	0.016	-9999	-0.29	3	3
Syndecan-4/TFPI	-0.043	0.096	-9999	-0.47	31	31

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.004	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0.008	-10000	0	-10000	0	0
SMAD4	-0.001	0.025	-10000	0	-0.8	1	1
DKK2	-0.022	0.13	-10000	0	-0.77	30	30
TLE1	-0.002	0.072	-10000	0	-0.8	8	8
MACF1	0	0.002	-10000	0	-10000	0	0
CTNNB1	0.1	0.087	-10000	0	-10000	0	0
WIF1	-0.42	0.4	-10000	0	-0.79	554	554
beta catenin/RanBP3	0.014	0.079	0.38	39	-10000	0	39
KREMEN2	-0.14	0.14	-10000	0	-0.29	500	500
DKK1	-0.079	0.19	-10000	0	-0.42	194	194
beta catenin/beta TrCP1	0.1	0.084	-10000	0	-10000	0	0
FZD1	0	0.001	-10000	0	-10000	0	0
AXIN2	-0.016	0.22	-10000	0	-1.6	20	20
AXIN1	0.007	0.006	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.007	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.078	0.3	1	-0.5	6	7
Axin1/APC/GSK3	0.001	0.014	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.077	0.033	-10000	0	-10000	0	0
HNF1A	0.002	0.028	-10000	0	-0.3	3	3
CTBP1	0.004	0.016	-10000	0	-10000	0	0
MYC	-0.019	0.23	-10000	0	-1.5	24	24
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.083	0.11	-10000	0	-0.61	28	28
NKD1	-0.009	0.07	-10000	0	-0.43	22	22
TCF4	-0.003	0.076	-10000	0	-0.8	9	9
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.007	-10000	0	-10000	0	0
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.015	0.1	0.45	44	-0.43	1	45
LEF1	-0.033	0.1	-10000	0	-0.3	119	119
DVL1	0.072	0.065	0.22	1	-10000	0	1
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.099	0.09	-10000	0	-0.58	5	5
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.58	53	53
LRP6	0	0.013	-10000	0	-0.29	2	2
CSNK1A1	0.005	0.018	-10000	0	-10000	0	0
NLK	0.01	0.014	-10000	0	-0.3	2	2
CCND1	0.001	0.11	-10000	0	-1.6	4	4
WNT1	0	0.013	-10000	0	-10000	0	0
GSK3A	0.006	0.006	-10000	0	-10000	0	0
GSK3B	0	0.001	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.044	0.045	0.31	9	-10000	0	9
APC	0	0.008	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.14	0.13	0.27	540	-10000	0	540
CREBBP	0.004	0.016	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.036	0.12	-10000	0	-0.59	40	40
FYN	0.015	0.18	-10000	0	-0.72	46	46
LAT/GRAP2/SLP76	-0.029	0.15	-10000	0	-0.66	42	42
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	0.03	0.12	-10000	0	-0.47	43	43
B2M	0.011	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.027	-10000	0	-0.16	2	2
MAP3K8	-0.006	0.066	-10000	0	-0.74	8	8
mol:Ca2+	-0.025	0.048	-10000	0	-0.12	203	203
integrin-mediated signaling pathway	-0.002	0.029	-10000	0	-0.54	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.021	0.18	-10000	0	-0.7	45	45
TRPV6	-0.16	0.32	-10000	0	-0.78	216	216
CD28	-0.008	0.071	-10000	0	-0.52	16	16
SHC1	0.01	0.18	-10000	0	-0.78	42	42
receptor internalization	-0.002	0.2	-10000	0	-0.8	49	49
PRF1	-0.002	0.23	-10000	0	-1.1	35	35
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2	0	0.009	-10000	0	-0.29	1	1
COT/AKT1	0.032	0.1	-10000	0	-0.38	44	44
LAT	0.008	0.19	-10000	0	-0.78	44	44
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.49	73	73
CD3E	-0.018	0.14	-10000	0	-0.51	60	60
CD3G	-0.033	0.16	-10000	0	-0.56	77	77
RASGRP2	-0.006	0.039	-10000	0	-0.18	44	44
RASGRP1	0.035	0.12	-10000	0	-0.46	45	45
HLA-A	0.009	0.027	-10000	0	-0.29	8	8
RASSF5	-0.003	0.044	-10000	0	-0.8	3	3
RAP1A/GTP/RAPL	-0.002	0.029	-10000	0	-0.54	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.043	-10000	0	-0.12	39	39
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.015	0.048	-10000	0	-0.24	29	29
PRKCA	-0.013	0.086	-10000	0	-0.31	57	57
GRAP2	-0.015	0.11	-10000	0	-0.73	21	21
mol:IP3	0.019	0.15	0.27	174	-0.45	41	215
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.007	0.21	-10000	0	-0.92	40	40
ORAI1	0.079	0.15	0.38	202	-10000	0	202
CSK	0.008	0.19	-10000	0	-0.8	41	41
B7 family/CD28	-0.026	0.18	-10000	0	-0.66	59	59
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.003	0.22	-10000	0	-0.77	60	60
PTPN6	0.007	0.19	-10000	0	-0.76	45	45
VAV1	0.009	0.19	-10000	0	-0.77	44	44
Monovalent TCR/CD3	-0.031	0.21	-10000	0	-0.68	68	68
CBL	0	0	-10000	0	-10000	0	0
LCK	0.009	0.2	-10000	0	-0.76	48	48
PAG1	0.008	0.19	-10000	0	-0.79	43	43
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.003	0.22	-10000	0	-0.78	57	57
CD80	-0.077	0.13	-10000	0	-0.29	278	278
CD86	-0.002	0.022	-10000	0	-0.29	6	6
PDK1/CARD11/BCL10/MALT1	-0.018	0.058	-10000	0	-0.28	35	35
HRAS	-0.003	0.027	-10000	0	-0.29	9	9
GO:0035030	-0.037	0.14	-10000	0	-0.54	57	57
CD8A	-0.001	0.079	-10000	0	-0.38	34	34
CD8B	-0.023	0.15	-10000	0	-0.6	55	55
PTPRC	-0.002	0.078	-10000	0	-0.5	20	20
PDK1/PKC theta	0.033	0.16	-10000	0	-0.6	45	45
CSK/PAG1	0.013	0.18	-10000	0	-0.78	40	40
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.016	-10000	0	-10000	0	0
GRAP2/SLP76	-0.036	0.17	-10000	0	-0.75	45	45
STIM1	0.041	0.079	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.054	-10000	0	-0.18	31	31
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.006	0.23	-10000	0	-0.89	49	49
mol:DAG	-0.008	0.1	-10000	0	-0.41	42	42
RAP1A/GDP	0.015	0.019	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.012	0.12	-10000	0	-0.59	37	37
cytotoxic T cell degranulation	0.001	0.21	-10000	0	-0.97	38	38
RAP1A/GTP	-0.003	0.014	-10000	0	-0.068	27	27
mol:PI-3-4-5-P3	0.026	0.14	-10000	0	-0.55	46	46
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.18	0.29	165	-0.61	42	207
NRAS	-0.001	0.013	-10000	0	-10000	0	0
ZAP70	-0.03	0.12	-10000	0	-0.8	20	20
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.026	0.14	-10000	0	-0.63	42	42
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.033	0.14	-10000	0	-0.57	53	53
CARD11	-0.007	0.052	-10000	0	-0.8	2	2
PRKCB	-0.012	0.085	-10000	0	-0.33	45	45
PRKCE	-0.006	0.069	-10000	0	-0.29	34	34
PRKCQ	0.023	0.18	-10000	0	-0.68	48	48
LCP2	0	0.009	-10000	0	-0.29	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.031	0.1	-10000	0	-0.39	43	43
IKK complex	0.041	0.045	-10000	0	-0.12	27	27
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.036	0.081	-10000	0	-0.29	37	37
PDPK1	0.033	0.12	-10000	0	-0.45	40	40
TCR/CD3/MHC I/CD8/Fyn	-0.007	0.24	-10000	0	-0.94	49	49

×

Regulation of Androgen receptor activity

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
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.005	0.02	-9999	-0.56	1	1
REL	-0.006	0.091	-9999	-0.8	13	13
HDAC7	0.009	0.13	-9999	-0.59	14	14
JUN	-0.005	0.066	-9999	-0.8	7	7
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.025	-9999	-0.8	1	1
KAT5	0.002	0.005	-9999	-10000	0	0
MAPK14	0.008	0.09	-9999	-0.62	20	20
FOXO1	-0.008	0.079	-9999	-0.8	10	10
T-DHT/AR	-0.004	0.13	-9999	-0.59	17	17
MAP2K6	-0.008	0.11	-9999	-0.79	21	21
BRM/BAF57	-0.001	0.011	-9999	-10000	0	0
MAP2K4	0.007	0.026	-9999	-0.81	1	1
SMARCA2	0	0	-9999	-10000	0	0
PDE9A	-0.09	0.29	-9999	-1.2	62	62
NCOA2	-0.035	0.16	-9999	-0.8	45	45
CEBPA	-0.005	0.075	-9999	-0.8	9	9
EHMT2	0.002	0.004	-9999	-10000	0	0
cell proliferation	0.014	0.14	-9999	-0.51	22	22
NR0B1	-0.01	0.053	-9999	-0.29	36	36
EGR1	-0.26	0.37	-9999	-0.8	328	328
RXRs/9cRA	-0.12	0.21	-9999	-0.49	256	256
AR/RACK1/Src	-0.003	0.11	-9999	-0.49	28	28
AR/GR	-0.052	0.13	-9999	-0.45	49	49
GNB2L1	0.001	0.004	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.29	1	1
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.014	0.061	-9999	-0.62	9	9
T-DHT/AR/TIF2/CARM1	-0.014	0.15	-9999	-0.52	65	65
SRC	0.022	0.09	-9999	-0.47	28	28
NR3C1	-0.011	0.093	-9999	-0.8	14	14
KLK3	-0.22	0.43	-9999	-1.2	158	158
APPBP2	0	0.016	-9999	-10000	0	0
TRIM24	0.004	0.011	-9999	-0.29	1	1
T-DHT/AR/TIP60	-0.026	0.095	-9999	-0.52	28	28
TMPRSS2	-0.17	0.42	-9999	-1.2	135	135
RXRG	-0.2	0.35	-9999	-0.8	259	259
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.001	0.004	-9999	-10000	0	0
NR2C2	-0.008	0.079	-9999	-0.8	10	10
KLK2	-0.041	0.24	-9999	-0.76	92	92
AR	-0.026	0.14	-9999	-0.35	139	139
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
MDM2	0.005	0.023	-9999	-0.29	4	4
SRY	0.004	0.01	-9999	-10000	0	0
GATA2	-0.026	0.13	-9999	-0.63	42	42
MYST2	0.002	0.01	-9999	-0.29	1	1
HOXB13	-0.13	0.15	-9999	-0.29	475	475
T-DHT/AR/RACK1/Src	-0.013	0.1	-9999	-0.5	28	28
positive regulation of transcription	-0.026	0.13	-9999	-0.63	42	42
DNAJA1	0.001	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.014	-9999	-10000	0	0
NCOA1	0.012	0.027	-9999	-0.83	1	1
SPDEF	-0.06	0.21	-9999	-0.65	103	103
T-DHT/AR/TIF2	0.013	0.099	-9999	-0.5	18	18
T-DHT/AR/Hsp90	-0.033	0.091	-9999	-0.52	28	28
GSK3B	0.005	0.006	-9999	-10000	0	0
NR2C1	0.003	0.006	-9999	-10000	0	0
mol:T-DHT	0.015	0.095	-9999	-0.51	28	28
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.006	0.014	-9999	-10000	0	0
POU2F1	0.021	0.026	-9999	-0.42	1	1
T-DHT/AR/DAX-1	-0.035	0.096	-9999	-0.53	28	28
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	-0.001	0.016	-9999	-0.3	3	3

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.003	0.033	-10000	0	-0.8	1	1
SVIL	-0.005	0.054	-10000	0	-0.8	4	4
ZNF318	0.024	0.059	0.22	1	-10000	0	1
JMJD2C	-0.003	0.041	-10000	0	-0.12	98	98
T-DHT/AR/Ubc9	-0.079	0.18	-10000	0	-0.55	132	132
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.002	0.012	-10000	0	-0.29	1	1
PELP1	0.005	0.013	-10000	0	-10000	0	0
CTNNB1	0	0.015	-10000	0	-10000	0	0
AKT1	0.008	0.019	-10000	0	-10000	0	0
PTK2B	0	0.013	-10000	0	-10000	0	0
MED1	0.002	0.048	-10000	0	-0.29	20	20
MAK	0.013	0.11	0.22	9	-0.59	20	29
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.006	0.064	-10000	0	-0.8	6	6
GSN	-0.013	0.092	-10000	0	-0.8	13	13
NCOA2	-0.035	0.16	-10000	0	-0.8	45	45
NCOA6	-0.002	0.021	-10000	0	-0.29	1	1
DNA-PK	0.024	0.06	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0	0.015	-10000	0	-10000	0	0
cell proliferation	-0.007	0.12	-10000	0	-0.91	12	12
XRCC5	0.007	0.016	-10000	0	-10000	0	0
UBE3A	-0.006	0.032	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.092	0.21	-10000	0	-0.59	145	145
FHL2	-0.017	0.13	-10000	0	-1.3	6	6
RANBP9	-0.001	0.019	-10000	0	-10000	0	0
JMJD1A	-0.011	0.056	-10000	0	-0.14	147	147
CDK6	-0.008	0.087	-10000	0	-0.73	14	14
TGFB1I1	-0.004	0.048	-10000	0	-0.8	3	3
T-DHT/AR/CyclinD1	-0.092	0.19	-10000	0	-0.56	137	137
XRCC6	0.007	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.065	0.21	-10000	0	-0.54	148	148
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0.016	0.04	-10000	0	-10000	0	0
BRCA1	-0.003	0.035	-10000	0	-0.49	3	3
TCF4	0.006	0.081	-10000	0	-0.8	9	9
CDKN2A	-0.041	0.11	-10000	0	-0.29	154	154
SRF	0.024	0.02	-10000	0	-10000	0	0
NKX3-1	-0.081	0.19	-10000	0	-1.3	19	19
KLK3	-0.2	0.53	-10000	0	-1.6	135	135
TMF1	0	0	-10000	0	-10000	0	0
HNRNPA1	0.009	0.022	-10000	0	-10000	0	0
AOF2	-0.009	0.024	-10000	0	-0.072	135	135
APPL1	0.035	0.034	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.071	0.19	-10000	0	-0.55	131	131
AR	-0.099	0.27	-10000	0	-0.81	132	132
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.009	0.022	-10000	0	-10000	0	0
PAWR	-0.001	0.025	-10000	0	-0.8	1	1
PRKDC	0.006	0.024	-10000	0	-0.29	3	3
PA2G4	0.012	0.029	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.067	0.18	-10000	0	-0.51	131	131
RPS6KA3	-0.009	0.073	-10000	0	-0.8	8	8
T-DHT/AR/ARA70	-0.084	0.18	-10000	0	-0.55	132	132
LATS2	0.01	0.024	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.061	0.18	0.19	1	-0.51	131	132
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.011	0.078	-10000	0	-0.44	25	25
KLK2	-0.12	0.32	-10000	0	-1.2	76	76
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.096	0.2	-10000	0	-0.54	162	162
TMPRSS2	-0.18	0.4	-10000	0	-1.2	133	133
CCND1	-0.016	0.074	-10000	0	-0.34	42	42
PIAS1	-0.006	0.032	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.034	-10000	0	-0.079	177	177
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.013	0.051	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.082	0.2	-10000	0	-0.56	142	142
CMTM2	0.004	0.013	-10000	0	-0.29	1	1
SNURF	-0.02	0.13	-10000	0	-0.8	26	26
ZMIZ1	0.004	0.031	-10000	0	-0.36	1	1
CCND3	0.002	0.011	-10000	0	-10000	0	0
TGIF1	0.009	0.022	-10000	0	-10000	0	0
FKBP4	-0.004	0.034	-10000	0	-0.3	9	9

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.005	0.13	-10000	0	-0.39	60	60
TBX21	-0.013	0.35	-10000	0	-1.3	52	52
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.004	0.073	-10000	0	-0.32	42	42
GADD45B	0.033	0.22	-10000	0	-0.8	34	34
IL12RB2	-0.058	0.2	-10000	0	-0.44	175	175
GADD45G	0.023	0.22	-10000	0	-0.81	35	35
natural killer cell activation	0.007	0.017	-10000	0	-10000	0	0
RELB	-0.003	0.028	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.047	-10000	0	-0.29	25	25
IL2RA	-0.028	0.11	-10000	0	-0.8	14	14
IFNG	-0.041	0.1	-10000	0	-10000	0	0
STAT3 (dimer)	0.026	0.22	-10000	0	-0.65	55	55
HLA-DRB5	-0.018	0.096	-10000	0	-0.33	80	80
FASLG	0.004	0.29	-10000	0	-1.1	42	42
NF kappa B2 p52/RelB	-0.078	0.2	-10000	0	-0.8	51	51
CD4	0.008	0.006	-10000	0	-10000	0	0
SOCS1	-0.005	0.042	-10000	0	-0.8	1	1
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.027	0.14	-10000	0	-0.5	73	73
CD3E	-0.021	0.14	-10000	0	-0.51	60	60
CD3G	-0.034	0.17	-10000	0	-0.57	77	77
IL12Rbeta2/JAK2	-0.027	0.16	-10000	0	-0.6	55	55
CCL3	0.013	0.26	-10000	0	-1	37	37
CCL4	0.015	0.25	-10000	0	-0.98	34	34
HLA-A	0.009	0.028	-10000	0	-0.3	8	8
IL18/IL18R	0.022	0.14	-10000	0	-0.55	53	53
NOS2	0.019	0.25	-10000	0	-0.88	44	44
IL12/IL12R/TYK2/JAK2/SPHK2	-0.004	0.13	-10000	0	-0.41	53	53
IL1R1	0.002	0.3	-10000	0	-1.2	42	42
IL4	-0.005	0.018	-10000	0	-10000	0	0
JAK2	0.016	0.03	-10000	0	-0.81	1	1
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.031	0.25	-10000	0	-1	47	47
RAB7A	0.047	0.19	-10000	0	-0.7	29	29
lysosomal transport	0.048	0.19	-10000	0	-0.65	30	30
FOS	-0.35	0.66	-10000	0	-1.3	322	322
STAT4 (dimer)	0.022	0.26	-10000	0	-0.87	53	53
STAT5A (dimer)	-0.086	0.22	-10000	0	-0.79	56	56
GZMA	0.003	0.28	-10000	0	-1.1	37	37
GZMB	-0.007	0.3	-10000	0	-1.2	44	44
HLX	-0.001	0.013	-10000	0	-0.29	2	2
LCK	0.004	0.29	-10000	0	-0.88	61	61
TCR/CD3/MHC II/CD4	-0.064	0.2	-10000	0	-0.55	86	86
IL2/IL2R	-0.03	0.1	-10000	0	-0.48	38	38
MAPK14	0.037	0.22	-10000	0	-0.78	40	40
CCR5	0.026	0.22	-10000	0	-0.82	36	36
IL1B	0.004	0.1	-10000	0	-0.7	19	19
STAT6	0.026	0.087	-10000	0	-0.24	23	23
STAT4	-0.032	0.16	-10000	0	-0.79	42	42
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.039	-10000	0	-0.29	19	19
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0.009	-10000	0	-0.29	1	1
IL12B	-0.046	0.12	-10000	0	-0.28	202	202
CD8A	-0.002	0.079	-10000	0	-0.39	34	34
CD8B	-0.023	0.15	-10000	0	-0.58	58	58
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.005	0.13	0.39	60	-10000	0	60
IL2RB	-0.012	0.065	-10000	0	-0.31	41	41
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.24	-10000	0	-0.78	53	53
IL2RG	-0.018	0.088	-10000	0	-0.36	52	52
IL12	-0.054	0.17	-10000	0	-0.6	65	65
STAT5A	-0.006	0.07	-10000	0	-0.8	8	8
CD247	-0.013	0.12	-10000	0	-0.59	37	37
IL2	-0.002	0.025	-10000	0	-0.29	8	8
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.035	0.2	-10000	0	-0.69	76	76
IL12/IL12R/TYK2/JAK2	0.008	0.29	-10000	0	-0.84	67	67
MAP2K3	0.032	0.22	-10000	0	-0.78	40	40
RIPK2	-0.001	0.02	-10000	0	-0.29	5	5
MAP2K6	0.028	0.23	-10000	0	-0.77	44	44
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.027	-10000	0	-0.55	2	2
IL18RAP	-0.016	0.15	-10000	0	-0.74	42	42
IL12Rbeta1/TYK2	0.014	0.056	-10000	0	-0.65	2	2
EOMES	-0.022	0.18	-10000	0	-1.5	15	15
STAT1 (dimer)	0.029	0.22	-10000	0	-0.74	35	35
T cell proliferation	0.033	0.2	-10000	0	-0.62	52	52
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.81	17	17
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.062	0.17	-10000	0	-0.73	47	47
ATF2	0.044	0.21	-10000	0	-0.73	38	38

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.22	-9999	-0.48	275	275
TC10/GTP	-0.11	0.18	-9999	-0.42	260	260
Insulin Receptor/Insulin/IRS1/Shp2	-0.021	0.1	-9999	-0.5	43	43
HRAS	-0.003	0.027	-9999	-0.29	9	9
APS homodimer	-0.013	0.061	-9999	-0.29	48	48
GRB14	-0.1	0.22	-9999	-0.47	221	221
FOXO3	-0.014	0.067	-9999	-0.68	9	9
AKT1	-0.057	0.13	-9999	-0.52	11	11
INSR	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.2	0.35	-9999	-0.8	260	260
CRK	0	0	-9999	-10000	0	0
PTPN1	0.033	0.03	-9999	-10000	0	0
CAV1	-0.12	0.23	-9999	-0.52	242	242
CBL/APS/CAP/Crk-II/C3G	-0.12	0.2	-9999	-0.46	260	260
Insulin Receptor/Insulin/IRS1/NCK2	-0.021	0.1	-9999	-0.5	43	43
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.022	0.096	-9999	-0.44	53	53
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.056	-9999	-10000	0	0
RPS6KB1	-0.008	0.14	-9999	-0.47	11	11
PARD6A	-0.002	0.024	-9999	-10000	0	0
CBL	0	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	-0.008	0.079	-9999	-0.8	10	10
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.05	0.12	-9999	-0.49	11	11
HRAS/GTP	-0.016	0.075	-9999	-0.38	43	43
Insulin Receptor	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.019	0.093	-9999	-0.46	43	43
PRKCI	-0.013	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.063	0.14	-9999	-0.42	88	88
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.003	-9999	-10000	0	0
PI3K	-0.023	0.098	-9999	-0.44	53	53
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.004	-9999	-10000	0	0
HRAS/GDP	-0.002	0.018	-9999	-10000	0	0
AKT2	-0.057	0.13	-9999	-0.52	11	11
PRKCZ	-0.014	0.037	-9999	-0.61	1	1
SH2B2	-0.013	0.061	-9999	-0.29	48	48
SHC/SHIP	-0.018	0.087	-9999	-0.44	43	43
F2RL2	-0.058	0.15	-9999	-0.36	170	170
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.004	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.13	0.21	-9999	-0.49	260	260
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	-0.019	0.093	-9999	-0.47	43	43
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.01	0.075	-9999	-0.99	6	6
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.8	43	43
p62DOK/RasGAP	0	0.003	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	-0.019	0.092	-9999	-0.46	43	43
GRB2	0	0.009	-9999	-0.29	1	1
EIF4EBP1	-0.014	0.14	-9999	-0.47	23	23
PTPRA	0	0.001	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.013	0.065	-9999	-0.33	43	43
Insulin Receptor/Insulin/IRS1	-0.021	0.1	-9999	-0.51	43	43
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.026	0.075	-9999	-0.46	22	22

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.52	60	60
MAP3K8	-0.006	0.067	-9999	-0.74	8	8
FOS	-0.034	0.14	-9999	-0.46	35	35
PRKCA	-0.013	0.13	-9999	-0.78	29	29
PTPN7	-0.008	0.071	-9999	-0.33	18	18
HRAS	-0.003	0.027	-9999	-0.29	9	9
PRKCB	-0.011	0.11	-9999	-0.55	36	36
NRAS	-0.001	0.013	-9999	-10000	0	0
RAS family/GTP	-0.002	0.015	-9999	-10000	0	0
MAPK3	-0.007	0.073	-9999	-10000	0	0
MAP2K1	-0.012	0.14	-9999	-0.6	44	44
ELK1	-0.003	0.005	-9999	-10000	0	0
BRAF	-0.032	0.12	-9999	-0.57	44	44
mol:GTP	-0.002	0.003	-9999	-0.006	307	307
MAPK1	-0.007	0.073	-9999	-0.29	1	1
RAF1	-0.032	0.12	-9999	-0.57	44	44
KRAS	-0.001	0.013	-9999	-0.29	2	2

×

Osteopontin-mediated 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
IKK alpha homodimer	-0.037	0.085	-9999	-0.44	35	35
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.07	-9999	-0.47	5	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.046	0.075	-9999	-10000	0	0
AP1	-0.14	0.21	-9999	-0.58	115	115
ILK	-0.007	0.11	-9999	-0.47	35	35
bone resorption	-0.038	0.11	-9999	-0.67	18	18
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.004	0.091	-9999	-0.42	35	35
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.017	0.1	-9999	-0.61	28	28
alphaV/beta3 Integrin/Osteopontin	-0.05	0.11	-9999	-0.53	35	35
MAP3K1	-0.007	0.11	-9999	-0.49	35	35
JUN	-0.005	0.066	-9999	-0.8	7	7
MAPK3	0.009	0.11	-9999	-0.44	35	35
MAPK1	0.009	0.11	-9999	-0.44	35	35
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.002	0.13	-9999	-0.54	37	37
ITGB3	-0.028	0.14	-9999	-0.78	36	36
NFKBIA	0.022	0.1	-9999	-0.42	35	35
FOS	-0.24	0.37	-9999	-0.8	307	307
CD44	-0.001	0.016	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
PLAU	0.021	0.1	-9999	-0.49	5	5
NF kappa B1 p50/RelA	-0.022	0.066	-9999	-0.45	5	5
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.6	35	35
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.11	-9999	-0.48	35	35
VAV3	-0.003	0.11	-9999	-0.45	42	42
MAP3K14	-0.005	0.11	-9999	-0.48	35	35
ROCK2	-0.022	0.13	-9999	-0.8	28	28
SPP1	-0.075	0.12	-9999	-0.28	277	277
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.036	0.084	-9999	-0.41	42	42
MMP2	-0.074	0.21	-9999	-0.67	38	38

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.04	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.047	0.14	-9999	-0.61	46	46
STXBP1	-0.005	0.061	-9999	-0.8	6	6
ACh/CHRNA1	-0.062	0.081	-9999	-0.22	34	34
RAB3GAP2/RIMS1/UNC13B	-0.039	0.11	-9999	-0.53	46	46
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	-0.067	0.18	-9999	-0.44	159	159
mol:ACh	0.001	0.032	-9999	-0.15	36	36
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.038	0.095	-9999	-0.4	52	52
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.062	0.081	-9999	-0.22	34	34
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.098	0.14	-9999	-0.29	353	353
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.06	0.12	-9999	-0.53	47	47
SNAP25	-0.017	0.07	-9999	-0.38	36	36
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.089	0.18	-9999	-0.8	40	40
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.009	0.05	-9999	-0.54	6	6
STX1A/SNAP25 fragment 1/VAMP2	-0.038	0.095	-9999	-0.4	52	52

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.21	0.25	1	-0.57	158	159
AKT1	0.014	0.006	-10000	0	-10000	0	0
GSC	-0.038	0.3	-10000	0	-1.5	41	41
NKX2-5	-0.044	0.1	-10000	0	-0.28	161	161
muscle cell differentiation	0.007	0.05	0.77	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.006	0.04	-10000	0	-0.46	2	2
SMAD4	0.014	0.042	-10000	0	-0.84	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.21	0.26	-10000	0	-0.53	407	407
SMAD3/SMAD4/VDR	0.005	0.031	-10000	0	-0.44	2	2
MYC	-0.017	0.12	-10000	0	-0.81	23	23
CDKN2B	0.029	0.13	-10000	0	-1.5	7	7
AP1	-0.12	0.2	-10000	0	-0.42	308	308
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.016	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.001	0.041	-10000	0	-0.33	2	2
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.041	0.12	-10000	0	-0.28	185	185
SMAD3/SMAD4/GR	-0.01	0.072	-10000	0	-0.57	15	15
GATA3	-0.037	0.15	-10000	0	-0.8	37	37
SKI/SIN3/HDAC complex/NCoR1	0.002	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.051	0.12	-10000	0	-0.55	44	44
endothelial cell migration	-0.009	0.039	-10000	0	-10000	0	0
MAX	0.001	0.004	-10000	0	-10000	0	0
RBBP7	-0.002	0.025	-10000	0	-10000	0	0
RBBP4	0	0.025	-10000	0	-0.8	1	1
RUNX2	-0.004	0.035	-10000	0	-0.29	15	15
RUNX3	-0.005	0.063	-10000	0	-0.63	9	9
RUNX1	-0.001	0.025	-10000	0	-0.8	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.01	0.093	-10000	0	-0.81	14	14
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.051	0.079	-10000	0	-1.5	2	2
KAT2B	0	0.025	-10000	0	-0.8	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.028	0.07	-10000	0	-0.47	5	5
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.002	-10000	0	-10000	0	0
SERPINE1	0.009	0.039	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.002	0.038	-10000	0	-0.56	3	3
SMAD3/SMAD4/ATF3	-0.082	0.2	-10000	0	-0.57	149	149
SAP30	-0.001	0.018	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.005	0.023	-10000	0	-10000	0	0
JUN	-0.075	0.23	-10000	0	-0.41	308	308
SMAD3/SMAD4/IRF7	-0.018	0.065	-10000	0	-0.55	1	1
TFE3	0.017	0.006	-10000	0	-10000	0	0
COL1A2	0.029	0.1	-10000	0	-1.3	2	2
mesenchymal cell differentiation	0.004	0.034	0.55	1	-10000	0	1
DLX1	-0.059	0.14	-10000	0	-0.34	181	181
TCF3	0	0.009	-10000	0	-0.29	1	1
FOS	-0.22	0.37	-10000	0	-0.8	307	307
SMAD3/SMAD4/Max	-0.002	0.029	-10000	0	-0.56	1	1
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0.001	0.006	-10000	0	-10000	0	0
LAMC1	0.043	0.048	-10000	0	-0.63	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.028	-10000	0	-0.55	1	1
IRF7	-0.028	0.087	-10000	0	-0.3	91	91
ESR1	-0.16	0.29	-10000	0	-0.59	275	275
HNF4A	-0.005	0.038	-10000	0	-10000	0	0
MEF2C	0.002	0.092	-10000	0	-0.66	3	3
SMAD2-3/SMAD4	-0.003	0.033	-10000	0	-0.55	1	1
Cbp/p300/Src-1	0.003	0.022	-10000	0	-0.53	1	1
IGHV3OR16-13	-0.001	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.002	0.007	-10000	0	-10000	0	0
SKIL	-0.003	0.03	-10000	0	-0.29	11	11
HDAC1	0	0.002	-10000	0	-10000	0	0
HDAC2	0	0.002	-10000	0	-10000	0	0
SNIP1	0	0.002	-10000	0	-10000	0	0
GCN5L2	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.001	0.03	-10000	0	-0.55	1	1
MSG1/HSC70	-0.24	0.3	-10000	0	-0.61	407	407
SMAD2	0.015	0.021	-10000	0	-10000	0	0
SMAD3	0.015	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.035	0.037	-10000	0	-0.33	3	3
SMAD2/SMAD2/SMAD4	0.027	0.04	-10000	0	-1.1	1	1
NCOR1	0	0.025	-10000	0	-0.81	1	1
NCOA2	-0.035	0.16	-10000	0	-0.8	45	45
NCOA1	-0.001	0.025	-10000	0	-0.8	1	1
MYOD/E2A	-0.003	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.013	0.044	-10000	0	-0.42	2	2
IFNB1	0.013	0.089	-10000	0	-0.43	7	7
SMAD3/SMAD4/MEF2C	-0.026	0.072	-10000	0	-0.77	2	2
CITED1	-0.32	0.39	-10000	0	-0.78	422	422
SMAD2-3/SMAD4/ARC105	-0.001	0.029	-10000	0	-0.49	1	1
RBL1	-0.002	0.037	-10000	0	-0.55	4	4
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.045	0.064	-10000	0	-0.49	7	7
RUNX1-3/PEBPB2	-0.004	0.049	-10000	0	-0.61	6	6
SMAD7	-0.071	0.14	-10000	0	-0.53	12	12
MYC/MIZ-1	-0.013	0.092	-10000	0	-0.62	23	23
SMAD3/SMAD4	0.019	0.059	0.28	38	-0.45	1	39
IL10	0.019	0.12	-10000	0	-0.52	39	39
PIASy/HDAC complex	0.001	0.004	-10000	0	-10000	0	0
PIAS3	0.001	0.005	-10000	0	-10000	0	0
CDK2	0.002	0.008	-10000	0	-10000	0	0
IL5	0.014	0.11	-10000	0	-0.53	32	32
CDK4	0.001	0.018	-10000	0	-0.29	3	3
PIAS4	0.001	0.004	-10000	0	-10000	0	0
ATF3	-0.12	0.28	-10000	0	-0.8	148	148
SMAD3/SMAD4/SP1	0	0.033	-10000	0	-0.52	2	2
FOXG1	-0.022	0.075	-10000	0	-0.29	73	73
FOXO3	0.025	0.035	-10000	0	-0.61	3	3
FOXO1	0.02	0.063	-10000	0	-0.61	10	10
FOXO4	0.026	0.008	-10000	0	-10000	0	0
heart looping	0.003	0.092	-10000	0	-0.65	3	3
CEBPB	0.012	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.034	0.093	-10000	0	-0.56	19	19
MYOD1	-0.004	0.033	-10000	0	-0.29	14	14
SMAD3/SMAD4/HNF4	-0.006	0.036	-10000	0	-0.7	1	1
SMAD3/SMAD4/GATA3	-0.024	0.11	-10000	0	-0.58	37	37
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.03	-10000	0	-0.29	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0	0.051	-10000	0	-0.54	7	7
SMAD3/SMAD4/SP1-3	0.003	0.03	-10000	0	-0.46	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0.019	0.013	-10000	0	-10000	0	0
SIN3B	0	0.002	-10000	0	-10000	0	0
SIN3A	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.009	0.089	-10000	0	-0.5	5	5
ITGB5	0.053	0.046	-10000	0	-0.43	1	1
TGIF/SIN3/HDAC complex/CtBP	0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.072	0.19	-10000	0	-0.57	132	132
AR	-0.1	0.27	-10000	0	-0.8	132	132
negative regulation of cell growth	-0.026	0.074	-10000	0	-0.49	2	2
SMAD3/SMAD4/MYOD	-0.007	0.035	-10000	0	-0.55	1	1
E2F5	-0.006	0.04	-10000	0	-0.29	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.002	0.056	-10000	0	-0.55	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0	0.045	-10000	0	-0.34	4	4
TFDP1	-0.001	0.018	-10000	0	-0.29	4	4
SMAD3/SMAD4/AP1	-0.12	0.21	-10000	0	-0.42	308	308
SMAD3/SMAD4/RUNX2	-0.004	0.034	-10000	0	-0.55	1	1
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.002	0.035	-10000	0	-0.8	2	2

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.053	0.12	-9999	-0.62	4	4
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.18	0.29	-9999	-0.62	308	308
IFNAR2	0.01	0.005	-9999	-10000	0	0
AKT1	-0.038	0.11	-9999	-0.29	158	158
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.46	258	258
NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
EGF	-0.16	0.32	-9999	-0.8	202	202
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.065	0.088	-9999	-0.58	4	4
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.15	-9999	-0.29	528	528
WRN	0	0	-9999	-10000	0	0
SP1	0.011	0.005	-9999	-10000	0	0
SP3	0.007	0.006	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.05	0.077	-9999	-0.59	2	2
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.053	0.12	-9999	-0.64	4	4
CCND1	-0.046	0.13	-9999	-1.3	4	4
MAX	0.008	0.006	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-10000	0	0
RBBP4	-0.001	0.025	-9999	-0.8	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	0.008	0.021	-9999	-10000	0	0
CDKN1B	0.008	0.075	-9999	-0.88	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.29	4	4
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.004	0.006	-9999	-10000	0	0
JUN	0	0.067	-9999	-0.8	7	7
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.23	0.37	-9999	-0.8	307	307
IFN-gamma/IRF1	-0.025	0.063	-9999	-0.36	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.031	0.09	-9999	-0.29	112	112
Telomerase	-0.005	0.027	-9999	-10000	0	0
IRF1	0.007	0.021	-9999	-0.28	3	3
ESR1	-0.16	0.29	-9999	-0.58	276	276
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0.011	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.022	0.007	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.007	0.011	-9999	-0.29	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.016	-9999	-0.29	3	3
TERT/NF kappa B1/14-3-3	-0.064	0.1	-9999	-0.67	3	3
NR2F2	0.001	0.044	-9999	-0.8	3	3
MAPK3	0.014	0.019	-9999	-10000	0	0
MAPK1	0.014	0.019	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.29	1	1
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.29	0.39	-9999	-0.8	383	383
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.34	0.35	-9999	-0.67	519	519
MYC	-0.009	0.12	-9999	-0.8	23	23
IL2	0.004	0.027	-9999	-0.29	8	8
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
TGFB1	0	0.009	-9999	-0.29	1	1
TRF2/BLM	-0.018	0.051	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.061	0.086	-9999	-0.6	3	3
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.05	0.077	-9999	-0.59	2	2
Smad3/Myc	-0.012	0.078	-9999	-0.53	23	23
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.033	0.1	-9999	-10000	0	0
Telomerase/PinX1	-0.05	0.077	-9999	-0.59	2	2
Telomerase/AKT1/mTOR/p70S6K	0.003	0.055	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.05	0.077	-9999	-0.59	2	2
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.05	0.077	-9999	-0.59	2	2
E2F1	-0.084	0.14	-9999	-0.29	330	330
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.058	0.12	-9999	-10000	0	0
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-0.29	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.005	0.036	-10000	0	-0.29	15	15
GNB1/GNG2	-0.015	0.048	-10000	0	-0.19	65	65
AKT1	0.051	0.072	-10000	0	-0.2	60	60
EGF	-0.16	0.32	-10000	0	-0.8	202	202
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.01	0.052	-10000	0	-0.44	4	4
mol:Ca2+	0.047	0.099	-10000	0	-0.3	60	60
LYN	-0.01	0.049	-10000	0	-0.39	3	3
RhoA/GTP	-0.008	0.03	-10000	0	-0.14	5	5
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.053	0.11	-10000	0	-0.35	60	60
GNG2	-0.009	0.086	-10000	0	-0.8	12	12
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.055	-10000	0	-0.54	6	6
G beta5/gamma2	-0.019	0.064	-10000	0	-0.25	65	65
PRKCH	0.048	0.11	-10000	0	-0.35	60	60
DNM1	-0.006	0.066	-10000	0	-0.74	8	8
TXA2/TP beta/beta Arrestin3	-0.004	0.027	-10000	0	-0.31	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.031	0.15	-10000	0	-0.72	44	44
G12 family/GTP	-0.021	0.073	-10000	0	-0.31	60	60
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.003	0.05	-10000	0	-0.8	4	4
RhoA/GTP/ROCK1	-0.001	0.017	-10000	0	-0.54	1	1
mol:GDP	-0.036	0.08	0.34	23	-10000	0	23
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
PRKG1	-0.053	0.2	-10000	0	-0.8	69	69
mol:IP3	0.048	0.12	-10000	0	-0.38	60	60
cell morphogenesis	-0.001	0.017	-10000	0	-0.54	1	1
PLCB2	0.045	0.15	-10000	0	-0.52	60	60
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.004	0.062	-10000	0	-0.39	8	8
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.01	0.049	-10000	0	-0.39	3	3
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.003	0.031	-10000	0	-0.29	12	12
PRKCB1	0.045	0.12	-10000	0	-0.38	60	60
GNAQ	-0.002	0.035	-10000	0	-0.8	2	2
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.047	0.16	-10000	0	-0.55	60	60
LCK	-0.014	0.072	-10000	0	-0.45	17	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.057	-10000	0	-0.3	31	31
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.035	-10000	0	-0.29	7	7
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.055	-10000	0	-0.3	36	36
MAPK14	0.051	0.079	-10000	0	-0.23	60	60
TGM2/GTP	0.047	0.13	-10000	0	-0.43	60	60
MAPK11	0.051	0.082	-10000	0	-0.24	60	60
ARHGEF1	0.039	0.061	-10000	0	-0.18	60	60
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.05	0.12	-10000	0	-0.4	60	60
RAB11/GDP	-0.001	0.013	-10000	0	-0.29	2	2
ICAM1	0.046	0.092	-10000	0	-0.28	60	60
cAMP biosynthetic process	0.043	0.11	-10000	0	-0.36	60	60
Gq family/GTP/EBP50	0.006	0.036	-10000	0	-0.25	15	15
actin cytoskeleton reorganization	-0.001	0.017	-10000	0	-0.54	1	1
SRC	-0.01	0.049	-10000	0	-0.39	3	3
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.028	0.1	-10000	0	-0.31	40	40
VCAM1	0.044	0.1	-10000	0	-0.32	60	60
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.055	-10000	0	-0.54	6	6
platelet activation	0.066	0.1	-10000	0	-0.31	60	60
PGI2/IP	-0.002	0.021	-10000	0	-0.2	12	12
PRKACA	-0.015	0.07	-10000	0	-0.38	37	37
Gq family/GDP/G beta5/gamma2	0.027	0.057	-10000	0	-0.46	8	8
TXA2/TP beta/beta Arrestin2	-0.006	0.055	-10000	0	-0.66	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.065	-10000	0	-0.35	37	37
mol:DAG	0.047	0.13	-10000	0	-0.42	60	60
EGFR	-0.29	0.39	-10000	0	-0.8	383	383
TXA2/TP alpha	0.048	0.15	-10000	0	-0.5	60	60
Gq family/GTP	-0.003	0.034	-10000	0	-0.28	15	15
YES1	-0.01	0.05	-10000	0	-0.37	5	5
GNAI2/GTP	-0.011	0.056	-10000	0	-0.41	5	5
PGD2/DP	-0.024	0.12	-10000	0	-0.62	37	37
SLC9A3R1	-0.024	0.08	-10000	0	-0.29	87	87
FYN	-0.011	0.053	-10000	0	-0.41	6	6
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.034	-10000	0	-0.8	1	1
PGK/cGMP	-0.036	0.13	-10000	0	-0.54	69	69
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.017	0.08	-10000	0	-0.56	13	13
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.042	0.13	-10000	0	-0.36	77	77
PRKCB	0.043	0.12	-10000	0	-0.37	71	71
PRKCE	0.05	0.11	-10000	0	-0.35	60	60
PRKCD	0.048	0.12	-10000	0	-0.38	60	60
PRKCG	0.045	0.12	-10000	0	-0.39	60	60
muscle contraction	0.051	0.15	-10000	0	-0.5	60	60
PRKCZ	0.053	0.11	-10000	0	-0.35	60	60
ARR3	-0.002	0.025	-10000	0	-10000	0	0
TXA2/TP beta	-0.013	0.063	-10000	0	-0.35	19	19
PRKCQ	0.036	0.14	-10000	0	-0.38	90	90
MAPKKK cascade	0.045	0.14	-10000	0	-0.48	60	60
SELE	0.039	0.12	-10000	0	-0.42	60	60
TP beta/GNAI2/GDP/G beta/gamma	-0.016	0.079	-10000	0	-0.56	13	13
ROCK1	-0.001	0.025	-10000	0	-0.8	1	1
GNA14	-0.014	0.088	-10000	0	-0.46	31	31
chemotaxis	0.046	0.18	-10000	0	-0.63	60	60
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.002	0.035	-10000	0	-0.8	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.11	-9999	-0.78	21	21
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.025	-9999	-0.8	1	1
RAC1-CDC42/GTP/PAK family	-0.12	0.14	-9999	-0.28	466	466
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.025	-9999	-0.8	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.002	0.035	-9999	-0.8	2	2
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.001	0.026	-9999	-0.8	1	1
p38 alpha/TAB1	-0.006	0.033	-9999	-0.32	4	4
PRKG1	-0.053	0.2	-9999	-0.8	69	69
DUSP8	-0.003	0.044	-9999	-0.68	4	4
PGK/cGMP/p38 alpha	-0.032	0.1	-9999	-0.4	72	72
apoptosis	-0.006	0.032	-9999	-0.31	4	4
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.1	0.27	-9999	-0.8	133	133
PAK1	-0.007	0.044	-9999	-0.29	24	24
SRC	0	0.009	-9999	-0.29	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	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	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.018	0.067	-9999	-0.35	18	18
BLK	-0.041	0.11	-9999	-0.3	142	142
HCK	-0.004	0.032	-9999	-10000	0	0
MAP2K3	0	0.009	-9999	-0.29	1	1
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.016	-9999	-0.29	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.029	0.047	-9999	-0.34	4	4
positive regulation of innate immune response	0.025	0.073	-9999	-0.37	18	18
LCK	-0.02	0.1	-9999	-0.43	49	49
p38alpha-beta/MKP7	-0.011	0.053	-9999	-0.39	7	7
p38alpha-beta/MKP5	-0.011	0.053	-9999	-0.35	17	17
PGK/cGMP	-0.041	0.16	-9999	-0.62	69	69
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.058	0.14	-9999	-0.38	138	138
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.36	0.4	-9999	-0.8	466	466

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.004	0.066	-10000	0	-0.68	9	9
CDKN2C	0.006	0.039	-10000	0	-0.79	2	2
CDKN2A	-0.052	0.12	-10000	0	-0.3	179	179
CCND2	0.006	0.033	0.25	8	-0.16	12	20
RB1	-0.007	0.032	0.19	4	-0.25	8	12
CDK4	0.01	0.031	0.25	9	-10000	0	9
CDK6	0.006	0.038	0.27	8	-0.22	11	19
G1/S progression	-0.006	0.036	0.25	8	-0.19	4	12

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.059	0.076	-9999	-0.41	6	6
EPHB2	-0.005	0.039	-9999	-0.29	19	19
Syndecan-2/TACI	-0.017	0.076	-9999	-0.53	18	18
LAMA1	-0.094	0.26	-9999	-0.79	123	123
Syndecan-2/alpha2 ITGB1	-0.13	0.22	-9999	-0.47	275	275
HRAS	-0.003	0.027	-9999	-0.29	9	9
Syndecan-2/CASK	-0.002	0.03	-9999	-0.54	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.034	0.059	-9999	-0.51	11	11
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.027	-9999	-0.48	3	3
LAMA3	-0.2	0.35	-9999	-0.8	259	259
EZR	-0.001	0.016	-9999	-0.29	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.098	0.26	-9999	-0.8	127	127
Syndecan-2/MMP2	-0.007	0.07	-9999	-0.67	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.015	0.096	-9999	-0.61	26	26
dendrite morphogenesis	-0.005	0.035	-9999	-0.52	3	3
Syndecan-2/GM-CSF	-0.005	0.037	-9999	-0.53	3	3
determination of left/right symmetry	0.017	0.036	-9999	-0.37	7	7
Syndecan-2/PKC delta	-0.002	0.03	-9999	-0.53	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.036	-9999	-0.48	3	3
MAPK1	0.022	0.036	-9999	-0.48	3	3
Syndecan-2/RACK1	-0.003	0.028	-9999	-0.46	3	3
NF1	-0.001	0.025	-9999	-0.8	1	1
FGFR/FGF/Syndecan-2	0.017	0.036	-9999	-0.37	7	7
ITGA2	-0.02	0.13	-9999	-0.8	26	26
MAPK8	0.028	0.062	-9999	-0.56	11	11
Syndecan-2/alpha2/beta1 Integrin	-0.065	0.18	-9999	-0.51	131	131
Syndecan-2/Kininogen	-0.005	0.036	-9999	-0.53	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.003	0.026	-9999	-0.42	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.027	-9999	-0.49	3	3
extracellular matrix organization	-0.002	0.03	-9999	-0.52	3	3
actin cytoskeleton reorganization	-0.059	0.075	-9999	-0.41	6	6
Syndecan-2/Caveolin-2/Ras	-0.062	0.16	-9999	-0.49	127	127
Syndecan-2/Laminin alpha3	-0.14	0.23	-9999	-0.53	262	262
Syndecan-2/RasGAP	-0.003	0.026	-9999	-0.43	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.29	1	1
Syndecan-2 dimer	-0.005	0.035	-9999	-0.53	3	3
GO:0007205	0	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.024	-9999	-0.41	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.026	0.11	-9999	-0.8	15	15
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.015	0.096	-9999	-0.61	26	26
Syndecan-2/Synbindin	-0.002	0.03	-9999	-0.53	3	3
TGFB1	0	0.009	-9999	-0.29	1	1
CASP3	0.03	0.029	-9999	-0.48	3	3
FN1	-0.12	0.14	-9999	-0.29	414	414
Syndecan-2/IL8	-0.021	0.085	-9999	-0.53	23	23
SDC2	0.017	0.036	-9999	-0.37	7	7
KNG1	-0.005	0.039	-9999	-0.29	19	19
Syndecan-2/Neurofibromin	-0.003	0.034	-9999	-0.53	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.006	0.043	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.002	0.03	-9999	-0.53	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.027	-9999	-0.49	3	3
Syndecan-2/Ezrin	-0.002	0.027	-9999	-0.48	3	3
PRKACA	0.03	0.033	-9999	-0.48	4	4
angiogenesis	-0.021	0.084	-9999	-0.53	23	23
MMP2	-0.008	0.079	-9999	-0.8	10	10
IL8	-0.033	0.13	-9999	-0.41	84	84
calcineurin-NFAT signaling pathway	-0.017	0.076	-9999	-0.53	18	18

×

IL2 signaling events mediated by STAT5

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
GAB2	0.007	0.045	-9999	-0.38	11	11
ELF1	-0.011	0.049	-9999	-0.38	14	14
CCNA2	-0.12	0.14	-9999	-0.29	413	413
PIK3CA	0.01	0.01	-9999	-0.29	1	1
JAK3	-0.004	0.033	-9999	-0.29	14	14
PIK3R1	-0.008	0.078	-9999	-0.8	10	10
JAK1	0.01	0.025	-9999	-0.8	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.058	0.08	-9999	-0.61	8	8
SHC1	0.011	0.003	-9999	-10000	0	0
SP1	-0.005	0.043	-9999	-0.38	13	13
IL2RA	0.003	0.13	-9999	-1	14	14
IL2RB	-0.012	0.065	-9999	-0.31	41	41
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.018	0.087	-9999	-0.36	52	52
G1/S transition of mitotic cell cycle	0.004	0.14	-9999	-0.84	21	21
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.016	0.12	-9999	-1	13	13
LCK	-0.02	0.1	-9999	-0.42	49	49
GRB2	0	0.009	-9999	-0.29	1	1
IL2	-0.002	0.025	-9999	-0.29	8	8
CDK6	-0.01	0.087	-9999	-0.73	14	14
CCND3	0.063	0.07	-9999	-0.58	5	5

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.004	0.11	-10000	0	-0.44	35	35
IKBKB	0.016	0.053	-10000	0	-0.27	2	2
AKT1	0.003	0.082	0.25	2	-0.27	23	25
IKBKG	0.018	0.055	-10000	0	-0.28	3	3
CALM1	-0.011	0.093	-10000	0	-0.45	29	29
PIK3CA	0	0.009	-10000	0	-0.29	1	1
MAP3K1	-0.009	0.15	-10000	0	-0.66	31	31
MAP3K7	0	0.009	-10000	0	-0.29	1	1
mol:Ca2+	-0.02	0.098	-10000	0	-0.48	29	29
DOK1	-0.001	0.018	-10000	0	-0.29	4	4
AP-1	-0.041	0.11	-10000	0	-0.26	75	75
LYN	0	0	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.21	-10000	0	-0.64	112	112
CD22	-0.062	0.18	-10000	0	-0.55	96	96
CAMK2G	-0.002	0.087	-10000	0	-0.5	16	16
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.047	0.14	-10000	0	-0.78	15	15
GO:0007205	-0.02	0.099	-10000	0	-0.49	29	29
SYK	0	0.009	-10000	0	-0.29	1	1
ELK1	-0.011	0.094	-10000	0	-0.46	29	29
NFATC1	-0.017	0.13	-10000	0	-0.58	32	32
B-cell antigen/BCR complex	-0.079	0.21	-10000	0	-0.64	112	112
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.009	0.1	-10000	0	-0.47	30	30
NFKBIA	0.016	0.02	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.058	0.16	-10000	0	-0.53	95	95
mol:GDP	-0.02	0.092	-10000	0	-0.46	29	29
PTEN	-0.002	0.035	-10000	0	-0.8	2	2
CD79B	-0.028	0.14	-10000	0	-0.6	48	48
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
PI3K/BCAP/CD19	-0.027	0.16	-10000	0	-0.48	95	95
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.03	0.098	-10000	0	-0.5	29	29
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.22	-10000	0	-0.45	327	327
CHUK	0.018	0.055	-10000	0	-0.28	3	3
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.023	0.078	-10000	0	-0.48	17	17
PTPN6	-0.057	0.17	-10000	0	-0.75	39	39
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.07	0.17	-10000	0	-0.81	32	32
ubiquitin-dependent protein catabolic process	0.019	0.019	-10000	0	-10000	0	0
BTK	-0.004	0.006	-10000	0	-10000	0	0
CD19	-0.081	0.18	-10000	0	-0.54	93	93
MAP4K1	-0.013	0.067	-10000	0	-0.31	44	44
CD72	-0.009	0.054	-10000	0	-0.31	30	30
PAG1	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0.002	0.13	-10000	0	-0.55	30	30
SH3BP5	0	0	-10000	0	-10000	0	0
PIK3AP1	-0.011	0.11	-10000	0	-0.54	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.042	0.13	-10000	0	-0.48	81	81
RAF1	-0.001	0.097	-10000	0	-0.44	29	29
RasGAP/p62DOK/SHIP	-0.055	0.16	-10000	0	-0.5	95	95
CD79A	-0.082	0.22	-10000	0	-0.8	79	79
re-entry into mitotic cell cycle	-0.04	0.11	-10000	0	-0.25	82	82
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.016	0.083	-10000	0	-0.43	16	16
MAPK1	0.016	0.083	-10000	0	-0.43	16	16
CD72/SHP1	-0.055	0.16	-10000	0	-0.7	38	38
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.13	-10000	0	-0.52	38	38
actin cytoskeleton organization	-0.026	0.15	-10000	0	-0.65	32	32
NF-kappa-B/RelA	0.043	0.032	-10000	0	-10000	0	0
Calcineurin	-0.02	0.072	-10000	0	-0.44	16	16
PI3K	-0.058	0.13	-10000	0	-0.54	41	41
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.032	0.11	-10000	0	-0.57	29	29
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.048	0.17	-10000	0	-0.84	34	34
DAPP1	-0.051	0.2	-10000	0	-0.98	33	33
cytokine secretion	-0.015	0.12	-10000	0	-0.52	33	33
mol:DAG	-0.03	0.098	-10000	0	-0.5	29	29
PLCG2	-0.002	0.036	-10000	0	-0.63	3	3
MAP2K1	0.008	0.091	-10000	0	-0.48	16	16
B-cell antigen/BCR complex/FcgammaRIIB	-0.069	0.19	-10000	0	-0.62	95	95
mol:PI-3-4-5-P3	-0.043	0.093	0.34	2	-0.36	41	43
ETS1	0.004	0.09	-10000	0	-0.49	19	19
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.057	0.16	-10000	0	-0.52	93	93
B-cell antigen/BCR complex/LYN	-0.058	0.19	-10000	0	-0.58	93	93
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0.001	-10000	0	-10000	0	0
RAC1	-0.029	0.16	-10000	0	-0.71	32	32
B-cell antigen/BCR complex/LYN/SYK	-0.058	0.18	-10000	0	-0.78	36	36
CARD11	-0.015	0.1	-10000	0	-0.49	29	29
FCGR2B	-0.003	0.051	-10000	0	-0.8	4	4
PPP3CA	-0.001	0.013	-10000	0	-0.29	2	2
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	-10000	0	-10000	0	0
PTPRC	-0.01	0.077	-10000	0	-0.5	20	20
PDPK1	-0.028	0.063	0.22	2	-0.27	23	25
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.014	-10000	0	-0.14	1	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.026	0.031	-9999	-10000	0	0
BIRC5	-0.21	0.13	-9999	-0.29	743	743
NFKBIA	-0.024	0.034	-9999	-10000	0	0
CPEB1	-0.15	0.31	-9999	-0.8	194	194
AKT1	-0.024	0.034	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.024	0.033	-9999	-0.56	1	1
NDEL1/TACC3	-0.039	0.059	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.003	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.03	0.039	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-0.29	4	4
JUB	-0.003	0.05	-9999	-0.8	4	4
TPX2	-0.11	0.1	-9999	-10000	0	0
TP53	-0.011	0.016	-9999	-10000	0	0
DLG7	-0.03	0.036	-9999	-10000	0	0
AURKAIP1	-0.003	0.031	-9999	-0.29	12	12
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.042	0.063	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.023	0.033	-9999	-0.55	1	1
AURKA	-0.037	0.045	-9999	-10000	0	0
AURKB	-0.008	0.01	-9999	-10000	0	0
CDC25B	-0.018	0.025	-9999	-10000	0	0
G2/M transition checkpoint	-0.025	0.04	-9999	-0.5	4	4
mRNA polyadenylation	-0.12	0.2	-9999	-0.53	193	193
Aurora A/CPEB	-0.12	0.2	-9999	-0.53	193	193
Aurora A/TACC1/TRAP/chTOG	-0.031	0.088	-9999	-0.48	37	37
BRCA1	-0.001	0.028	-9999	-0.46	3	3
centrosome duplication	-0.029	0.039	-9999	-10000	0	0
regulation of centrosome cycle	-0.039	0.059	-9999	-10000	0	0
spindle assembly	-0.031	0.087	-9999	-0.48	37	37
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.071	-9999	-0.62	1	1
CENPA	-0.004	0.011	-9999	-10000	0	0
Aurora A/PP2A	-0.026	0.031	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.006	0.029	-9999	-10000	0	0
negative regulation of DNA binding	-0.009	0.019	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.013	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.025	0.041	-9999	-0.51	4	4
mitotic prometaphase	-0.013	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.037	0.045	-9999	-10000	0	0
TACC1	-0.029	0.15	-9999	-0.8	37	37
TACC3	-0.044	0.1	-9999	-0.29	159	159
Aurora A/Antizyme1	-0.021	0.025	-9999	-10000	0	0
Aurora A/RasGAP	-0.026	0.031	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.003	0.003	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.004	0.023	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.11	0.1	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.088	-9999	-10000	0	0
PAK1	-0.007	0.044	-9999	-0.29	24	24
CKAP5	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.44	0.4	-10000	0	-0.8	572	572
CLTC	0.027	0.017	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	0.02	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.006	0.027	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.017	-10000	0	-10000	0	0
CPE	0.005	0.084	-10000	0	-0.54	24	24
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.002	0.019	-10000	0	-10000	0	0
CTNND1	0.025	0.031	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.03	0.014	-10000	0	-10000	0	0
TSHR	-0.007	0.11	-10000	0	-0.54	45	45
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.007	0.075	-10000	0	-0.8	9	9
mol:Choline	-0.002	0.019	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.036	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.027	-10000	0	-10000	0	0
JUP	0.025	0.017	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.005	0.048	-10000	0	-0.49	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.016	0.053	-10000	0	-0.38	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-0.29	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.004	0.036	-10000	0	-0.29	16	16
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.034	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.005	-10000	0	-10000	0	0
ACAP1	-0.001	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.021	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0.001	-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	0.025	0.03	-10000	0	-10000	0	0
NME1	0.01	0.037	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.017	-10000	0	-10000	0	0
IL2RA	0.017	0.044	-10000	0	-0.37	7	7
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.22	0.2	-10000	0	-0.4	572	572
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.003	0.032	-10000	0	-0.34	9	9
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.014	-10000	0	-10000	0	0
SDC1	0.021	0.024	-10000	0	-0.35	1	1
ARF6/GDP	-0.007	0.033	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.035	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.019	-10000	0	-10000	0	0
endocytosis	0.005	0.048	0.48	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.073	0.2	-10000	0	-0.43	239	239
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.025	-10000	0	-0.8	1	1
Dynamin 2/GDP	-0.006	0.027	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.14	0.23	-10000	0	-0.43	390	390
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.008	0.03	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.001	0.004	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.01	0.076	-9999	-0.56	19	19
forebrain development	-0.025	0.2	-9999	-0.51	130	130
GNAO1	-0.029	0.14	-9999	-0.48	66	66
SMO/beta Arrestin2	-0.005	0.054	-9999	-0.62	8	8
SMO	0.004	0.072	-9999	-0.75	9	9
ARRB2	0.01	0.004	-9999	-10000	0	0
GLI3/SPOP	-0.002	0.035	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.002	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.037	0.17	-9999	-0.8	50	50
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.055	0.16	-9999	-0.49	91	91
SAP30	0	0.018	-9999	-0.29	4	4
mol:GDP	0.004	0.072	-9999	-0.75	9	9
MIM/GLI2A	0.002	0.029	-9999	-0.29	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.002	0.005	-9999	-10000	0	0
GLI2	0.04	0.036	-9999	-10000	0	0
GLI3	0.039	0.04	-9999	-0.3	12	12
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.004	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.009	0.086	-9999	-0.8	12	12
Gi family/GTP	-0.022	0.095	-9999	-0.36	47	47
SIN3B	0.001	0.004	-9999	-10000	0	0
SIN3A	0.001	0.004	-9999	-10000	0	0
GLI3/Su(fu)	-0.002	0.026	-9999	-0.45	1	1
GLI2/Su(fu)	0.007	0.046	-9999	-0.39	6	6
FOXA2	-0.012	0.032	-9999	-10000	0	0
neural tube patterning	-0.025	0.2	-9999	-0.51	130	130
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.026	-9999	-0.46	1	1
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.002	0.029	-9999	-0.29	9	9
embryonic limb morphogenesis	-0.025	0.2	-9999	-0.51	130	130
SUFU	-0.003	0.029	-9999	-0.31	9	9
LGALS3	-0.01	0.089	-9999	-0.8	13	13
catabolic process	-0.004	0.027	-9999	-10000	0	0
GLI3A/CBP	-0.021	0.096	-9999	-0.38	68	68
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.027	0.21	-9999	-0.53	130	130
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.025	-9999	-0.8	1	1
RBBP7	-0.001	0.026	-9999	-10000	0	0
Su(fu)/Galectin3	-0.008	0.065	-9999	-0.54	14	14
GNAZ	-0.005	0.075	-9999	-0.8	9	9
RBBP4	0	0.025	-9999	-0.8	1	1
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.004	0.026	-9999	-10000	0	0
STK36	0.011	0.026	-9999	-0.8	1	1
Gi family/GNB1/GNG2/GDP	-0.028	0.099	-9999	-0.47	25	25
PTCH1	-0.068	0.35	-9999	-1.2	78	78
MIM/GLI1	-0.052	0.18	-9999	-0.49	130	130
CREBBP	-0.021	0.096	-9999	-0.38	68	68
Su(fu)/SIN3/HDAC complex	0.006	0.021	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.075	-10000	0	-0.75	10	10
positive regulation of NF-kappaB transcription factor activity	-0.065	0.19	-10000	0	-0.61	110	110
MAP2K4	0.041	0.039	-10000	0	-0.38	2	2
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.005	0.061	-10000	0	-0.8	6	6
SMPD1	-0.003	0.027	-10000	0	-0.29	9	9
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.079	0.24	-10000	0	-0.8	102	102
TRAIL/TRAILR2	-0.006	0.057	-10000	0	-0.61	9	9
TRAIL/TRAILR3	-0.009	0.071	-10000	0	-0.66	11	11
TRAIL/TRAILR1	-0.009	0.074	-10000	0	-0.61	15	15
TRAIL/TRAILR4	-0.065	0.19	-10000	0	-0.61	110	110
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.059	-10000	0	-0.49	15	15
IKK complex	-0.003	0.02	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0.006	-10000	0	-0.2	1	1
MAPK3	0.017	0.059	-10000	0	-0.61	9	9
MAP3K1	-0.004	0.033	-10000	0	-0.32	10	10
TRAILR4 (trimer)	-0.078	0.24	-10000	0	-0.8	102	102
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.005	0.061	-10000	0	-0.8	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.039	-10000	0	-0.33	15	15
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.059	-10000	0	-0.61	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.008	0.056	-10000	0	-0.46	15	15
mol:ceramide	-0.003	0.027	-10000	0	-0.28	9	9
FADD	-0.004	0.035	-10000	0	-0.29	15	15
MAPK8	0.044	0.057	-10000	0	-0.45	9	9
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
TRAILR3 (trimer)	-0.005	0.05	-10000	0	-0.43	11	11
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.066	-10000	0	-0.54	15	15
DAP3	0	0.009	-10000	0	-0.29	1	1
CASP10	0.021	0.11	0.31	96	-0.5	13	109
JNK cascade	-0.065	0.19	-10000	0	-0.61	110	110
TRAIL (trimer)	-0.007	0.075	-10000	0	-0.75	10	10
TNFRSF10C	-0.005	0.05	-10000	0	-0.43	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.008	0.057	-10000	0	-0.46	15	15
TRAIL/TRAILR2/FADD	-0.007	0.052	-10000	0	-0.53	9	9
cell death	-0.003	0.026	-10000	0	-0.28	9	9
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.03	-10000	0	-0.32	9	9
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.015	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.005	0.043	-10000	0	-0.45	9	9

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.011	0.056	-9999	-0.29	41	41
GPC2	-0.035	0.1	-9999	-0.8	3	3
GPC2/Midkine	-0.03	0.079	-9999	-0.41	17	17
neuron projection morphogenesis	-0.03	0.079	-9999	-0.41	17	17

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.017	0.093	-9999	-0.53	33	33
E-cadherin/beta catenin	-0.019	0.11	-9999	-0.61	32	32
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.001	0.026	-9999	-0.55	2	2
CDH1	-0.025	0.14	-9999	-0.8	32	32

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.001	0.008	-10000	0	-10000	0	0
CDKN1B	0.036	0.025	-10000	0	-0.43	3	3
CDKN1A	0.036	0.021	-10000	0	-0.43	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
FOXO3	0.036	0.025	-10000	0	-0.43	3	3
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	-0.001	0.013	-10000	0	-0.29	2	2
AKT3	0.009	0.058	-10000	0	-0.44	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.003	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.026	-10000	0	-0.42	4	4
BAD/YWHAZ	-0.001	0.01	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.025	0.41	4	-10000	0	4
TSC1	0.037	0.003	-10000	0	-10000	0	0
YWHAZ	-0.001	0.016	-10000	0	-0.29	3	3
AKT1/RAF1	0	0.001	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.037	0.003	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.021	0.042	-10000	0	-0.52	6	6
MAP3K5	-0.003	0.05	-10000	0	-0.8	4	4
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.021	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.003	-10000	0	-10000	0	0
CASP9	0.037	0.003	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.022	-10000	0	-0.4	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
AKT2/p21CIP1	-0.001	0.018	-10000	0	-0.41	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.003	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.004	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.054	0.029	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.037	0.009	-10000	0	-10000	0	0
MAPKKK cascade	0	0.001	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.005	-10000	0	-10000	0	0
TSC1/TSC2	0.044	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.005	-10000	0	-10000	0	0
glucose import	-0.25	0.26	-10000	0	-0.48	575	575
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.25	0.26	-10000	0	-0.48	575	575
GSK3A	0.037	0.003	-10000	0	-10000	0	0
FOXO1	0.033	0.046	-10000	0	-0.43	10	10
GSK3B	0.037	0.003	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.5	31	31
G1/S transition of mitotic cell cycle	0.044	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.043	0.031	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.022	0.02	-10000	0	-0.61	1	1
MAP4K4	0.041	0.047	-10000	0	-0.69	1	1
BAG4	-0.006	0.057	-10000	0	-0.8	4	4
PKC zeta/ceramide	-0.023	0.048	0.18	1	-0.58	1	2
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.08	-10000	0	-0.8	9	9
BAX	-0.008	0.021	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.009	-10000	0	-10000	0	0
BAD	-0.022	0.046	0.2	1	-0.25	1	2
SMPD1	0.025	0.034	-10000	0	-0.25	14	14
RB1	-0.022	0.047	0.2	1	-0.48	1	2
FADD/Caspase 8	0.048	0.048	-10000	0	-0.65	1	1
MAP2K4	-0.014	0.047	-10000	0	-0.46	2	2
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.014	0.046	-10000	0	-0.46	1	1
EGF	-0.16	0.32	-10000	0	-0.8	202	202
mol:ceramide	-0.033	0.048	0.21	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.021	0.023	-10000	0	-0.61	1	1
ASAH1	-0.001	0.016	-10000	0	-0.29	3	3
negative regulation of cell cycle	-0.022	0.047	0.2	1	-0.48	1	2
cell proliferation	-0.095	0.16	-10000	0	-0.39	231	231
BID	0.023	0.035	-10000	0	-0.4	1	1
MAP3K1	-0.022	0.047	0.2	1	-0.48	1	2
EIF2A	-0.005	0.041	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.002	0.043	-10000	0	-0.42	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.002	0.043	-10000	0	-0.42	1	1
Cathepsin D/ceramide	-0.028	0.05	0.18	1	-0.25	2	3
FADD	0.039	0.05	-10000	0	-0.47	3	3
KSR1	-0.022	0.048	0.2	1	-0.33	3	4
MAPK8	-0.012	0.055	0.2	1	-0.35	10	11
PRKRA	-0.022	0.045	0.2	1	-10000	0	1
PDGFA	-0.001	0.025	-10000	0	-0.8	1	1
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
IGF1	-0.18	0.33	-10000	0	-0.8	231	231
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.033	0.047	0.21	1	-10000	0	1
CTSD	-0.011	0.055	-10000	0	-0.29	39	39
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.1	0.17	-10000	0	-0.42	231	231
PRKCD	0	0.009	-10000	0	-0.29	1	1
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.023	-10000	0	-0.61	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.001	0.025	-10000	0	-0.8	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.006	0.043	-10000	0	-0.73	1	1
TNFR1A/BAG4/TNF-alpha	-0.014	0.074	-10000	0	-0.54	18	18
mol:Sphingosine-1-phosphate	0.022	0.02	-10000	0	-0.61	1	1
MAP2K1	-0.005	0.044	-10000	0	-0.43	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.007	0.044	0.18	25	-10000	0	25
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.004	0.042	-10000	0	-0.61	4	4
EIF2AK2	-0.013	0.043	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.01	0.064	-10000	0	-0.53	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.021	-10000	0	-0.33	1	1
MAP2K2	-0.005	0.044	-10000	0	-0.43	1	1
SMPD3	0.025	0.043	-10000	0	-0.28	18	18
TNF	-0.018	0.1	-10000	0	-0.48	38	38
PKC zeta/PAR4	-0.001	0.027	-10000	0	-0.61	2	2
mol:PHOSPHOCHOLINE	0.044	0.11	0.27	201	-10000	0	201
NF kappa B1/RelA/I kappa B alpha	-0.001	0.02	-10000	0	-0.45	2	2
AIFM1	-0.007	0.044	0.18	25	-10000	0	25
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

Retinoic acid receptors-mediated signaling

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	0	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	-0.001	0.016	-10000	0	-0.53	1	1
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.037	0.04	-10000	0	-0.32	4	4
KAT2B	-0.001	0.025	-10000	0	-0.8	1	1
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.02	0.05	0.24	4	-0.34	12	16
RAR alpha/9cRA/Cyclin H	-0.012	0.065	-10000	0	-0.38	27	27
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.034	0.05	-10000	0	-0.32	14	14
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.012	0.071	-10000	0	-0.64	9	9
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.006	0.12	-10000	0	-0.57	31	31
NCOA2	-0.035	0.16	-10000	0	-0.8	45	45
NCOA3	0	0.009	-10000	0	-10000	0	0
NCOA1	-0.001	0.025	-10000	0	-0.8	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.009	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.071	-10000	0	-0.8	8	8
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.043	0.11	-10000	0	-0.63	27	27
RARA	0.014	0.064	-10000	0	-0.32	34	34
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.021	0.084	-10000	0	-0.3	56	56
PRKCA	-0.008	0.13	-10000	0	-0.77	29	29
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.006	0.13	-10000	0	-0.58	33	33
RXRG	-0.1	0.21	-10000	0	-0.45	277	277
RXRA	0.022	0.066	-10000	0	-0.33	34	34
RXRB	0.01	0.076	-10000	0	-0.44	27	27
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.024	0.096	-10000	0	-0.34	75	75
CRBP1/9-cic-RA	-0.017	0.069	-10000	0	-0.24	75	75
RARB	0.003	0.091	-10000	0	-0.8	13	13
PRKCG	-0.002	0.059	-10000	0	-0.29	43	43
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.12	-10000	0	-0.61	31	31
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.012	0.1	-10000	0	-0.49	32	32
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.057	-10000	0	-0.45	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.006	0.13	-10000	0	-0.58	34	34
positive regulation of DNA binding	-0.011	0.062	-10000	0	-0.36	27	27
NRIP1	-0.004	0.12	-10000	0	-0.62	22	22
RXRs/RARs	-0.013	0.13	-10000	0	-0.57	34	34
RXRs/RXRs/DNA/9cRA	-0.046	0.12	-10000	0	-0.66	27	27
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.006	0.036	-10000	0	-0.52	1	1
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	-0.01	0.076	-10000	0	-0.61	16	16
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.024	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.028	0.072	-10000	0	-0.49	17	17
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	-0.001	0.009	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.001	0.011	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-0.29	1	1
BRCA1	-0.001	0.028	-10000	0	-0.46	3	3
CCNE1	-0.059	0.12	-10000	0	-0.29	210	210
CDK2/Cyclin E1	-0.037	0.074	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.011	0.079	-10000	0	-0.61	17	17
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.05	0.11	-10000	0	-10000	0	0
DNA repair	0.008	0.093	-10000	0	-0.47	6	6
BRCA1/BARD1/ubiquitin	-0.011	0.079	-10000	0	-0.61	17	17
BARD1/DNA-PK	-0.008	0.06	-10000	0	-0.48	16	16
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.01	0.076	0.61	16	-10000	0	16
BRCA1/BARD1/CTIP/M/R/N Complex	-0.005	0.039	-10000	0	-0.32	16	16
BRCA1/BACH1/BARD1/TopBP1	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/P53	-0.008	0.061	-10000	0	-0.48	17	17
BARD1/CSTF1/BRCA1	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BACH1	-0.001	0.028	-10000	0	-0.46	3	3
BARD1	-0.013	0.099	-10000	0	-0.77	17	17
PCNA	-0.001	0.016	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/UbcH7	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/RAD51/PCNA	-0.052	0.085	-10000	0	-0.53	17	17
BARD1/DNA-PK/P53	-0.007	0.056	-10000	0	-0.45	16	16
BRCA1/BARD1/Ubiquitin	-0.011	0.079	-10000	0	-0.61	17	17
BRCA1/BARD1/CTIP	-0.008	0.061	-10000	0	-0.48	17	17
FA complex	-0.005	0.011	-10000	0	-10000	0	0
BARD1/EWS	-0.01	0.076	-10000	0	-0.61	16	16
RBBP8	0.022	0.006	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.008	0.061	0.48	17	-10000	0	17
BRCA1/BARD1	-0.028	0.073	-10000	0	-0.49	17	17
CSTF1	0	0.009	-10000	0	-0.29	1	1
BARD1/EWS-Fli1	-0.01	0.077	-10000	0	-0.62	16	16
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-0.29	386	386
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.011	0.079	-10000	0	-0.61	17	17
EWSR1	0	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.006	0.094	-10000	0	-0.46	33	33
ACTA1	-0.017	0.13	0.27	1	-0.66	32	33
NUMA1	0.006	0.094	-10000	0	-0.46	33	33
SPTAN1	-0.003	0.13	-10000	0	-0.64	31	31
LIMK1	-0.004	0.13	-10000	0	-0.64	31	31
BIRC3	-0.01	0.08	-10000	0	-0.8	9	9
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
CASP10	-0.014	0.14	-10000	0	-0.68	34	34
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.006	0.094	-10000	0	-0.46	33	33
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.003	0.12	-10000	0	-0.62	31	31
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.009	0.14	-10000	0	-0.64	40	40
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.013	0.088	-10000	0	-0.69	15	15
BID	0.005	0.061	-10000	0	-0.3	33	33
MAP3K1	0.005	0.042	-10000	0	-0.28	8	8
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.004	0.13	-10000	0	-0.64	31	31
CASP9	0.001	0.003	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	0.18	7	-0.22	5	12
neuron apoptosis	0.022	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.12	-10000	0	-0.61	31	31
APAF1	0	0.002	-10000	0	-10000	0	0
CASP6	0.023	0.057	-10000	0	-0.42	4	4
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
ICAD/CAD	0.004	0.12	-10000	0	-0.61	31	31
CASP7	-0.007	0.037	0.35	9	-10000	0	9
KRT18	0.016	0.016	-10000	0	-10000	0	0
apoptosis	0.01	0.11	0.3	1	-0.54	31	32
DFFA	-0.003	0.13	-10000	0	-0.64	31	31
DFFB	-0.003	0.13	-10000	0	-0.64	31	31
PARP1	0.002	0.031	0.22	5	-0.18	7	12
actin filament polymerization	-0.003	0.12	0.57	34	-10000	0	34
TNF	-0.018	0.1	-10000	0	-0.48	38	38
CYCS	0.008	0.049	-10000	0	-0.22	32	32
SATB1	0.017	0.1	-10000	0	-0.49	28	28
SLK	-0.003	0.13	-10000	0	-0.64	31	31
p15 BID/BAX	-0.014	0.049	-10000	0	-0.34	9	9
CASP2	0.043	0.041	-10000	0	-0.46	1	1
JNK cascade	-0.005	0.042	0.28	8	-10000	0	8
CASP3	-0.012	0.13	0.29	1	-0.65	34	35
LMNB2	0.04	0.038	-10000	0	-0.35	3	3
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.025	-10000	0	-0.8	1	1
Mammalian IAPs/DIABLO	-0.006	0.046	-10000	0	-0.48	9	9
negative regulation of DNA binding	0.013	0.087	-10000	0	-0.68	15	15
stress fiber formation	-0.003	0.12	-10000	0	-0.62	31	31
GZMB	-0.028	0.15	-10000	0	-0.66	42	42
CASP1	0.014	0.035	-10000	0	-0.44	6	6
LMNB1	0.044	0.038	-10000	0	-0.35	3	3
APP	0.022	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.004	0.1	0.3	1	-0.52	31	32
LMNA	0.04	0.038	-10000	0	-0.35	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.037	-10000	0	-0.49	1	1
LRDD	-0.001	0.018	-10000	0	-10000	0	0
SREBF1	-0.006	0.13	-10000	0	-0.64	31	31
APAF-1/Caspase 9	-0.004	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.006	0.093	-10000	0	-0.46	33	33
CFL2	0.003	0.12	-10000	0	-0.59	34	34
GAS2	-0.049	0.19	-10000	0	-0.52	123	123
positive regulation of apoptosis	0.045	0.038	-10000	0	-0.38	2	2
PRF1	-0.018	0.11	-10000	0	-0.64	29	29

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.002	0.036	-10000	0	-0.8	2	2
ANTXR2	-0.009	0.082	-10000	0	-0.8	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.1	12	12
monocyte activation	0.003	0.075	-10000	0	-0.46	26	26
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.009	-10000	0	-10000	0	0
MAP2K7	-0.001	0.009	-10000	0	-10000	0	0
MAP2K6	-0.01	0.067	-10000	0	-0.48	20	20
CYAA	0.01	0.057	-10000	0	-0.5	12	12
MAP2K4	-0.001	0.018	-10000	0	-0.48	1	1
IL1B	0.007	0.066	-10000	0	-0.35	30	30
Channel	-0.006	0.059	-10000	0	-0.54	12	12
NLRP1	-0.008	0.06	-10000	0	-0.5	15	15
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.1	12	-10000	0	12
MAPK3	-0.001	0.009	-10000	0	-10000	0	0
MAPK1	-0.001	0.009	-10000	0	-10000	0	0
PGR	-0.14	0.21	-10000	0	-0.48	294	294
PA/Cellular Receptors	-0.007	0.064	-10000	0	-0.58	12	12
apoptosis	-0.001	0.011	-10000	0	-0.1	12	12
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.006	0.055	-10000	0	-0.5	12	12
macrophage activation	0.02	0.01	-10000	0	-10000	0	0
TNF	-0.018	0.1	-10000	0	-0.48	38	38
VCAM1	-0.012	0.073	-10000	0	-0.46	26	26
platelet activation	-0.001	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.014	0.021	0.2	3	-10000	0	3
IL18	0.011	0.037	-10000	0	-0.22	15	15
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.1	12	12
LEF	-0.001	0.011	-10000	0	-0.1	12	12
CASP1	-0.005	0.03	-10000	0	-0.24	15	15
mol:cAMP	-0.001	0.013	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.1	12	12
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.006	0.056	-10000	0	-0.51	12	12
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.03	0.008	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.046	-9999	-10000	0	0
MAPK12	0.019	0.079	-9999	-0.47	24	24
CCND1	0.015	0.042	-9999	-0.23	23	23
p38 gamma/SNTA1	-0.011	0.068	-9999	-0.47	20	20
MAP2K3	0	0.009	-9999	-0.29	1	1
PKN1	0	0.009	-9999	-0.29	1	1
G2/M transition checkpoint	0.019	0.078	-9999	-0.47	24	24
MAP2K6	0.012	0.08	-9999	-0.5	24	24
MAPT	-0.018	0.14	-9999	-0.4	112	112
MAPK13	0.022	0.009	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.029	-9999	-0.44	4	4

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.064	-10000	0	-0.67	1	1
UGCG	-0.011	0.094	-10000	0	-0.82	13	13
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.091	-10000	0	-0.39	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.014	0.096	-10000	0	-0.81	13	13
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.091	-10000	0	-0.39	42	42
FRAP1	0.052	0.13	-10000	0	-0.41	64	64
FOXO3	0.06	0.11	-10000	0	-0.42	33	33
AKT1	0.055	0.11	-10000	0	-0.45	32	32
GAB2	0.007	0.045	-10000	0	-0.38	11	11
SMPD1	-0.002	0.014	-10000	0	-10000	0	0
SGMS1	-0.002	0.014	-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	0.016	0.055	-10000	0	-0.54	10	10
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.033	0.09	-10000	0	-0.36	36	36
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.006	0.06	-10000	0	-0.62	10	10
RPS6KB1	0.022	0.032	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	21	21
JAK3	0.009	0.035	-10000	0	-0.29	14	14
PIK3R1	0.005	0.08	-10000	0	-0.8	10	10
JAK1	0.012	0.026	-10000	0	-0.8	1	1
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.046	0.18	-10000	0	-0.94	28	28
MYB	0.01	0.18	-10000	0	-1.3	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.094	-10000	0	-0.59	10	10
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.021	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.053	0.092	-10000	0	-0.57	10	10
Rac1/GDP	-0.005	0.048	-10000	0	-0.49	10	10
T cell proliferation	0.058	0.088	-10000	0	-0.53	10	10
SHC1	0.011	0.004	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.01	-10000	0	-0.066	19	19
PRKCZ	0.058	0.091	-10000	0	-0.55	10	10
NF kappa B1 p50/RelA	-0.025	0.089	-10000	0	-0.49	15	15
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.039	0.069	-10000	0	-0.57	5	5
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.018	0.12	-10000	0	-0.74	16	16
IL2RB	0	0.067	-10000	0	-0.31	41	41
TERT	-0.042	0.1	-10000	0	-0.29	150	150
E2F1	0.022	0.064	-10000	0	-0.44	19	19
SOS1	0.011	0.004	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.03	19	-10000	0	19
PTPN11	0.011	0.004	-10000	0	-10000	0	0
IL2RG	-0.005	0.09	-10000	0	-0.36	52	52
actin cytoskeleton organization	0.058	0.088	-10000	0	-0.53	10	10
GRB2	0.011	0.01	-10000	0	-0.29	1	1
IL2	0.006	0.026	-10000	0	-0.29	8	8
PIK3CA	0.013	0.01	-10000	0	-0.28	1	1
Rac1/GTP	0.026	0.049	-10000	0	-0.46	10	10
LCK	-0.007	0.1	-10000	0	-0.42	49	49
BCL2	0.038	0.2	-10000	0	-0.86	42	42

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0.009	-9999	-10000	0	0
PLK4	-0.012	0.058	-9999	-0.29	44	44
regulation of centriole replication	0.013	0.042	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.017	0.085	-9999	-0.52	23	23
MAP4K1	-0.013	0.067	-9999	-0.31	44	44
MAP3K8	-0.006	0.066	-9999	-0.74	8	8
PRKCB	-0.019	0.11	-9999	-0.55	36	36
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.007	0.048	-9999	-0.47	4	4
JUN	0.017	0.11	-9999	-0.6	32	32
MAP3K7	-0.007	0.046	-9999	-0.49	3	3
GRAP2	-0.015	0.11	-9999	-0.73	21	21
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.043	0.057	-9999	-0.46	5	5
LAT	-0.005	0.048	-9999	-0.8	2	2
LCP2	0	0.009	-9999	-0.29	1	1
MAPK8	0.013	0.11	-9999	-0.69	25	25
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.05	-9999	-0.35	18	18
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.016	0.079	-9999	-0.49	23	23

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.019	0.1	-9999	-0.58	32	32
KLHL20	-0.009	0.033	-9999	-0.24	3	3
CYFIP2	-0.01	0.067	-9999	-0.36	30	30
Rac1/GDP	0.048	0.072	-9999	-0.35	32	32
ENAH	-0.018	0.1	-9999	-0.58	32	32
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.051	-9999	-0.5	1	1
ABI1/Sra1/Nap1	-0.006	0.025	-9999	-0.19	4	4
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.019	0.087	-9999	-0.48	34	34
RAPGEF1	0.037	0.094	-9999	-0.48	32	32
CTNND1	0	0.009	-9999	-0.29	1	1
regulation of calcium-dependent cell-cell adhesion	-0.019	0.1	-9999	-0.6	32	32
CRK	0.028	0.1	-9999	-0.54	32	32
E-cadherin/gamma catenin/alpha catenin	-0.017	0.093	-9999	-0.53	33	33
alphaE/beta7 Integrin	-0.006	0.04	-9999	-0.61	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.037	-9999	-0.49	6	6
DLG1	-0.018	0.1	-9999	-0.58	32	32
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.041	-9999	-0.32	2	2
MLLT4	-0.005	0.062	-9999	-0.73	7	7
ARF6/GTP/NME1/Tiam1	-0.007	0.028	-9999	-10000	0	0
PI3K	-0.011	0.053	-9999	-0.43	2	2
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.11	-9999	-0.61	33	33
TIAM1	-0.001	0.018	-9999	-0.29	4	4
E-cadherin(dimer)/Ca2+	-0.014	0.079	-9999	-0.46	32	32
AKT1	-0.006	0.03	-9999	-0.22	2	2
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
CDH1	-0.025	0.14	-9999	-0.8	32	32
RhoA/GDP	0.047	0.072	-9999	-0.35	32	32
actin cytoskeleton organization	-0.007	0.025	-9999	-0.18	3	3
CDC42/GDP	0.047	0.072	-9999	-0.35	32	32
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.011	0.059	-9999	-0.34	33	33
ITGB7	-0.009	0.058	-9999	-0.8	2	2
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.015	0.083	-9999	-0.48	32	32
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.014	0.08	-9999	-0.46	32	32
mol:GDP	0.045	0.083	-9999	-0.41	32	32
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.001	0.026	-9999	-0.55	2	2
p120 catenin/RhoA/GDP	-0.011	0.062	-9999	-0.35	32	32
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.007	0.029	-9999	-0.22	7	7
NME1	-0.014	0.063	-9999	-0.29	51	51
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.019	0.1	-9999	-0.57	33	33
regulation of cell-cell adhesion	-0.008	0.044	-9999	-0.42	1	1
WASF2	-0.003	0.013	-9999	-10000	0	0
Rap1/GTP	-0.011	0.058	-9999	-0.59	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.082	-9999	-0.45	35	35
CCND1	-0.009	0.036	-9999	-0.27	7	7
VAV2	0.033	0.098	-9999	-0.51	32	32
RAP1/GDP	-0.011	0.059	-9999	-0.57	1	1
adherens junction assembly	-0.018	0.098	-9999	-0.55	33	33
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.078	-9999	-0.42	35	35
E-cadherin/beta catenin	-0.015	0.086	-9999	-0.5	32	32
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.018	0.1	-9999	-0.58	32	32
PIK3CA	0	0.009	-9999	-0.29	1	1
Rac1/GTP	-0.012	0.054	-9999	-0.36	6	6
E-cadherin/beta catenin/alpha catenin	-0.016	0.092	-9999	-0.53	32	32
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.11	-9999	-0.62	32	32

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.007	0.043	-10000	0	-0.48	4	4
IRAK/TOLLIP	-0.001	0.01	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.031	0.12	-10000	0	-0.6	40	40
IL1A	-0.006	0.041	-10000	0	-0.29	21	21
IL1B	0.01	0.096	-10000	0	-0.7	17	17
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.014	-10000	0	-10000	0	0
IL1R2	-0.037	0.16	-10000	0	-0.57	68	68
IL1R1	-0.015	0.11	-10000	0	-0.8	20	20
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.001	0.063	0.24	31	-0.33	17	48
TOLLIP	0	0.009	-10000	0	-0.29	1	1
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.032	0.078	-10000	0	-0.38	34	34
MAP3K7	0	0.009	-10000	0	-0.29	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.021	0.11	-10000	0	-0.48	45	45
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.012	0.072	-10000	0	-0.5	20	20
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.011	0.068	-10000	0	-0.47	20	20
IL1 beta fragment/IL1R1/IL1RAP	-0.019	0.11	-10000	0	-0.56	35	35
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.028	0.072	-10000	0	-0.4	28	28
IRAK1	0.021	0.013	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.02	0.094	-10000	0	-0.61	22	22
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.006	0.06	-10000	0	-0.61	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.011	0.062	-10000	0	-0.37	21	21
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.019	0.11	-10000	0	-0.56	35	35
IL1 beta/IL1R2	-0.034	0.13	-10000	0	-0.57	53	53
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.019	0.094	-10000	0	-0.93	4	4
IRAK3	-0.03	0.15	-10000	0	-0.79	39	39
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.017	0.098	-10000	0	-0.5	35	35
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.048	-10000	0	-0.34	20	20
IL1 alpha/IL1R1/IL1RAP	-0.014	0.08	-10000	0	-0.55	20	20
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0.009	-10000	0	-0.29	1	1
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.008	-10000	0	-10000	0	0
IL1RAP	-0.001	0.025	-10000	0	-0.8	1	1
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.014	0.078	-10000	0	-0.82	4	4
CASP1	-0.004	0.056	-10000	0	-0.8	5	5
IL1RN/IL1R2	-0.035	0.12	-10000	0	-0.59	44	44
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.018	0.1	-10000	0	-0.52	35	35
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-0.29	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.008	0.054	-10000	0	-0.39	20	20
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL1RN	-0.012	0.065	-10000	0	-0.8	2	2
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.009	0.059	-10000	0	-0.42	20	20

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.022	0.076	0.51	6	-10000	0	6
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-10000	0	-0.54	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.031	0.13	-10000	0	-0.48	66	66
RhoA/GTP	-0.023	0.077	-10000	0	-0.52	6	6
negative regulation of cAMP metabolic process	-0.026	0.086	-10000	0	-0.37	35	35
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.059	-10000	0	-0.8	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.026	0.087	-10000	0	-0.37	35	35
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	50	50

×

S1P3 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
PDGFRB	-0.003	0.05	-9999	-0.8	4	4
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.028	0.093	-9999	-0.34	81	81
GNAO1	-0.019	0.14	-9999	-0.48	66	66
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-10000	0	0
AKT1	-0.011	0.052	-9999	-0.68	4	4
AKT3	0.015	0.19	-9999	-1.4	17	17
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.05	-9999	-0.8	4	4
GNAI2	0.012	0.002	-9999	-10000	0	0
GNAI3	0.012	0.002	-9999	-10000	0	0
GNAI1	-0.027	0.18	-9999	-0.81	50	50
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.028	-9999	-0.29	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.1	-9999	-0.39	38	38
MAPK3	0.02	0.099	-9999	-0.52	13	13
MAPK1	0.02	0.099	-9999	-0.52	13	13
JAK2	0.022	0.1	-9999	-0.48	16	16
CXCR4	0.016	0.1	-9999	-0.48	18	18
FLT1	0.013	0.026	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.019	0.099	-9999	-0.52	13	13
S1P/S1P3/Gi	0.012	0.1	-9999	-0.4	38	38
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.024	0.083	-9999	-0.5	13	13
VEGFA	0.01	0.031	-9999	-0.35	1	1
S1P/S1P2/Gi	0.01	0.098	-9999	-0.37	37	37
VEGFR1 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.64	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.006	0.041	-9999	-0.34	15	15
GNAQ	-0.002	0.035	-9999	-0.8	2	2
GNAZ	0.005	0.076	-9999	-0.8	9	9
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.014	0.088	-9999	-0.46	31	31
GNA15	-0.003	0.034	-9999	-0.8	1	1
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.035	-9999	-0.8	2	2
Rac1/GTP	-0.024	0.083	-9999	-0.5	13	13

×

p38 MAPK 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
TRAF6/ASK1	-0.002	0.029	-10000	0	-0.47	4	4
TRAF2/ASK1	-0.003	0.035	-10000	0	-0.54	4	4
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.025	0.046	-10000	0	-0.39	3	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.062	-10000	0	-0.39	8	8
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.035	0.094	-10000	0	-0.29	125	125
TXN	0.008	0.005	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	0	0	-10000	0	-10000	0	0
GADD45B	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K6	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K7	0	0.009	-10000	0	-0.29	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.003	0.043	-10000	0	-0.61	5	5
TAK1/TAB family	0.001	0.012	0.22	3	-10000	0	3
RAC1/OSM/MEKK3	0	0.006	-10000	0	-10000	0	0
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
RAC1/OSM/MEKK3/MKK3	-0.006	0.024	-10000	0	-0.4	1	1
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.07	0.21	-10000	0	-0.6	121	121
CCM2	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/CAMKIIB	-0.045	0.14	-10000	0	-0.54	74	74
MAPK11	-0.002	0.043	-10000	0	-0.8	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.042	0.13	-10000	0	-0.5	77	77
OSM/MEKK3	0	0.008	-10000	0	-10000	0	0
TAOK1	-0.003	0.094	-10000	0	-0.44	45	45
TAOK2	0.017	0	-10000	0	-10000	0	0
TAOK3	0.017	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.003	0.05	-10000	0	-0.8	4	4
MAP3K10	0	0.009	-10000	0	-0.29	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.002	0.033	-10000	0	-0.53	4	4
GADD45/MTK1/MTK1	-0.013	0.035	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.018	0.08	0.33	1	-0.36	52	53
FRAP1	0.011	0.021	-10000	0	-10000	0	0
AKT1	-0.016	0.069	0.24	1	-0.42	11	12
INSR	0	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.012	0.053	-10000	0	-0.34	11	11
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.017	-10000	0	-10000	0	0
TSC2	0	0.001	-10000	0	-10000	0	0
RHEB/GDP	-0.011	0.046	-10000	0	-0.31	11	11
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.017	0.084	-10000	0	-0.42	43	43
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.02	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.018	0.044	0.19	1	-0.26	11	12
MAP3K5	0.009	0.028	-10000	0	-0.44	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
apoptosis	0.009	0.028	-10000	0	-0.44	4	4
mol:LY294002	0	0	-10000	0	-0.002	43	43
EIF4B	0.025	0.04	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.007	0.029	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.02	0.086	-10000	0	-0.39	53	53
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.031	0.18	1	-0.19	10	11
FKBP1A	0	0.009	-10000	0	-0.29	1	1
RHEB/GTP	-0.01	0.046	-10000	0	-0.3	11	11
mol:Amino Acids	0	0	-10000	0	-0.002	43	43
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.016	0.072	0.26	1	-0.33	52	53
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.004	0.04	-10000	0	-0.63	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.013	0.057	-10000	0	-0.36	11	11
tumor necrosis factor receptor activity	0	0	0.002	43	-10000	0	43
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	-0.011	0.092	-10000	0	-0.45	43	43
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.035	-10000	0	-0.8	2	2
PDK2	-0.018	0.078	0.26	1	-0.34	55	56
EIF4EBP1	0.013	0.012	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PPP2R5D	0.018	0.02	-10000	0	-10000	0	0
peptide biosynthetic process	0	0.004	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-0.003	10	12
EEF2	0	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.007	0.052	-9999	-0.34	21	21
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.002	0.017	-9999	-0.36	2	2
GNAO1	-0.031	0.13	-9999	-0.48	66	66
mol:Sphinganine-1-P	0.017	0.039	-9999	-0.61	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.027	-9999	-0.29	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.015	-9999	-0.31	2	2
S1PR5	-0.008	0.059	-9999	-0.8	3	3
S1PR4	-0.015	0.081	-9999	-0.8	6	6
GNAI1	-0.039	0.17	-9999	-0.8	50	50
S1P/S1P5/G12	-0.005	0.033	-9999	-0.47	3	3
S1P/S1P3/Gq	-0.004	0.036	-9999	-0.29	15	15
S1P/S1P4/Gi	-0.026	0.083	-9999	-0.34	38	38
GNAQ	-0.002	0.035	-9999	-0.8	2	2
GNAZ	-0.007	0.075	-9999	-0.8	9	9
GNA14	-0.014	0.088	-9999	-0.46	31	31
GNA15	-0.003	0.034	-9999	-0.8	1	1
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.035	-9999	-0.8	2	2
ABCC1	0	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

Figure S105. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S105. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.004	0.025	-9999	-0.41	2	2
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin/MAdCAM1	-0.01	0.043	-9999	-0.46	3	3
EPO	-0.048	0.11	-9999	-0.29	171	171
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.03	0.068	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.04	-9999	-0.4	10	10
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.06	-9999	-0.61	10	10
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.01	0.025	-9999	-0.51	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
MADCAM1	-0.011	0.056	-9999	-0.29	41	41
cell adhesion	-0.01	0.043	-9999	-0.45	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.025	0.058	-9999	-0.48	12	12
ITGB7	-0.009	0.058	-9999	-0.8	2	2
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.059	-9999	-0.53	12	12
p130Cas/Crk/Dock1	-0.006	0.043	-9999	-0.4	12	12
VCAM1	-0.011	0.089	-9999	-0.63	18	18
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.014	-9999	-10000	0	0
BCAR1	0.033	0.055	-9999	-0.44	12	12
EPOR	0	0.009	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-10000	0	0
Rac1/GTP	-0.003	0.041	-9999	-0.42	10	10

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.049	0.029	-10000	0	-0.36	4	4
NFATC2	0.017	0.064	-10000	0	-0.32	10	10
NFATC3	0	0.016	-10000	0	-0.52	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.011	0.096	-10000	0	-0.4	35	35
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.019	0.078	-10000	0	-0.49	17	17
BCL2/BAX	-0.022	0.11	-10000	0	-0.62	36	36
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0	0	-10000	0	-10000	0	0
BAD	-0.001	0.013	-10000	0	-0.29	2	2
CABIN1/MEF2D	-0.02	0.082	-10000	0	-0.52	17	17
Calcineurin A alpha-beta B1/BCL2	-0.028	0.15	-10000	0	-0.8	36	36
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.02	0.081	0.52	17	-10000	0	17
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.03	0.088	-10000	0	-0.29	107	107
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.5	31	31
MAP3K8	-0.006	0.066	-10000	0	-0.74	8	8
NFAT4/CK1 alpha	-0.001	0.017	-10000	0	-0.39	2	2
MEF2D/NFAT1/Cbp/p300	-0.034	0.089	-10000	0	-0.47	2	2
CABIN1	0.011	0.097	-10000	0	-0.41	35	35
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.025	-10000	0	-0.8	1	1
CAMK4	-0.011	0.06	-10000	0	-0.8	1	1
mol:Ca2+	0	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.044	-10000	0	-0.61	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.006	0.07	-10000	0	-0.8	8	8
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-0.29	1	1
NFAT1-c-4/YWHAQ	-0.002	0.022	-10000	0	-0.41	1	1
PRKCH	-0.001	0.025	-10000	0	-0.8	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0	0	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-10000	0	-10000	0	0
apoptosis	-0.007	0.036	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.023	-10000	0	-10000	0	0
PRKCB	-0.019	0.11	-10000	0	-0.55	36	36
PRKCE	0	0	-10000	0	-10000	0	0
JNK2/NFAT4	0	0.014	-10000	0	-0.47	1	1
BAD/BCL-XL	0	0.008	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.29	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
PRKCA	-0.021	0.13	-10000	0	-0.77	29	29
PRKCG	-0.012	0.058	-10000	0	-0.29	43	43
PRKCQ	-0.039	0.17	-10000	0	-0.7	57	57
FKBP38/BCL2	-0.021	0.11	-10000	0	-0.61	36	36
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.048	0.049	-10000	0	-0.38	9	9
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.006	0.033	-10000	0	-0.54	1	1
NFATc/ERK1	0.049	0.033	-10000	0	-0.37	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.019	0.077	-10000	0	-0.49	17	17
NR4A1	-0.004	0.21	-10000	0	-0.71	81	81
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	0	0.016	-10000	0	-0.51	1	1
NFAT1/CK1 alpha	-0.015	0.039	-10000	0	-0.3	3	3
RCH1/ KPNB1	-0.019	0.056	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.015	0.067	-10000	0	-0.3	52	52
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.016	-10000	0	-0.29	3	3
NFATc/p38 alpha	0.051	0.031	-10000	0	-0.37	1	1
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.031	0.13	-9999	-0.48	66	66
CDC42/GTP	-0.024	0.076	-9999	-0.5	4	4
PLCG1	-0.025	0.079	-9999	-0.51	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.024	0.075	-9999	-0.48	4	4
S1PR5	-0.008	0.059	-9999	-0.8	3	3
S1PR4	-0.015	0.081	-9999	-0.8	6	6
MAPK3	-0.025	0.079	-9999	-0.51	4	4
MAPK1	-0.025	0.079	-9999	-0.51	4	4
S1P/S1P5/Gi	-0.026	0.087	-9999	-0.37	35	35
GNAI1	-0.039	0.17	-9999	-0.8	50	50
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-9999	-0.54	3	3
RHOA	-0.007	0.04	-9999	-0.45	6	6
S1P/S1P4/Gi	-0.028	0.086	-9999	-0.35	37	37
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.075	-9999	-0.8	9	9
S1P/S1P4/G12/G13	-0.007	0.044	-9999	-0.49	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.006	0.051	-10000	0	-0.48	12	12
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.013	-10000	0	-0.4	1	1
GATA1/HDAC4	-0.004	0.03	-10000	0	-0.61	1	1
GATA1/HDAC5	-0.003	0.023	-10000	0	-10000	0	0
GATA2/HDAC5	-0.019	0.1	-10000	0	-0.61	28	28
HDAC5/BCL6/BCoR	-0.004	0.043	-10000	0	-0.53	7	7
HDAC9	-0.01	0.077	-10000	0	-0.5	20	20
Glucocorticoid receptor/Hsp90/HDAC6	-0.007	0.061	-10000	0	-0.53	14	14
HDAC4/ANKRA2	-0.001	0.019	-10000	0	-0.61	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.026	0.13	-10000	0	-0.63	42	42
HDAC4/RFXANK	-0.001	0.023	-10000	0	-0.61	1	1
BCOR	-0.002	0.035	-10000	0	-0.8	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0.009	-10000	0	-0.29	1	1
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.007	0.066	-10000	0	-0.61	12	12
Histones	-0.003	0.024	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.025	-10000	0	-0.8	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.019	-10000	0	-0.61	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.013	-10000	0	-10000	0	0
CAMK4	-0.011	0.06	-10000	0	-0.8	1	1
Tubulin/HDAC6	-0.001	0.018	-10000	0	-0.53	1	1
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.005	0.037	-10000	0	-0.29	17	17
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.011	0.093	-10000	0	-0.8	14	14
SUMO1/HDAC4	0	0.014	-10000	0	-0.44	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.019	-10000	0	-0.61	1	1
Tubulin	-0.001	0.021	-10000	0	-0.61	1	1
HDAC4/14-3-3 E	-0.001	0.019	-10000	0	-0.61	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.004	0.05	-10000	0	-0.61	7	7
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.016	-10000	0	-0.53	1	1
HDAC4/SRF	-0.006	0.035	-10000	0	-0.53	2	2
HDAC4/ER alpha	-0.12	0.22	-10000	0	-0.61	159	159
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.024	-10000	0	-10000	0	0
cell motility	-0.001	0.017	-10000	0	-0.53	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.004	0.056	-10000	0	-0.8	5	5
HDAC4/CaMK II delta B	-0.001	0.025	-10000	0	-0.8	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.16	0.29	-10000	0	-0.58	276	276
HDAC6/HDAC11	-0.001	0.013	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.001	0.025	-10000	0	-0.8	1	1
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.02	-10000	0	-0.45	2	2
GNG2	-0.009	0.086	-10000	0	-0.8	12	12
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.028	-10000	0	-0.8	1	1
HDAC11	-0.001	0.02	-10000	0	-0.29	5	5
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.001	0.02	-10000	0	-0.29	5	5
nuclear import	0	0.014	0.44	1	-10000	0	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.61	35	35
AKT1	0.081	0.068	-9999	-0.68	6	6
PTK2B	-0.02	0.11	-9999	-1	7	7
VEGFR2 homodimer/Frs2	-0.008	0.08	-9999	-0.85	8	8
CAV1	-0.17	0.33	-9999	-0.8	224	224
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.008	0.075	-9999	-0.79	8	8
endothelial cell proliferation	0.083	0.084	-9999	-0.69	6	6
mol:Ca2+	0.05	0.072	-9999	-0.88	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.007	0.071	-9999	-0.95	5	5
RP11-342D11.1	0.042	0.072	-9999	-0.71	8	8
CDH5	-0.007	0.075	-9999	-0.8	9	9
VEGFA homodimer	-0.001	0.012	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.02	0.13	-9999	-0.8	26	26
HRAS/GDP	-0.005	0.057	-9999	-0.76	5	5
SH2D2A	-0.034	0.098	-9999	-0.3	120	120
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.003	0.053	-9999	-0.69	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.02	0.085	-9999	-0.75	10	10
VEGFR1 homodimer	-0.001	0.025	-9999	-0.8	1	1
SHC/GRB2/SOS1	-0.004	0.064	-9999	-0.85	5	5
GRB10	0.05	0.072	-9999	-0.88	5	5
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
PAK1	-0.007	0.044	-9999	-0.29	24	24
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.092	-9999	-1	7	7
HRAS	-0.003	0.027	-9999	-0.29	9	9
VEGF/Rho/ROCK1/Integrin Complex	-0.011	0.064	-9999	-0.59	7	7
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.007	0.069	-9999	-0.92	5	5
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.043	-9999	-0.8	3	3
Nck/Pak	-0.004	0.028	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.008	0.082	-9999	-0.82	9	9
mol:GDP	-0.004	0.061	-9999	-0.81	5	5
mol:NADP	0.073	0.05	-9999	-0.56	5	5
eNOS/Hsp90	0.075	0.047	-9999	-0.52	5	5
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:IP3	0.051	0.073	-9999	-0.9	5	5
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.026	-9999	-0.8	1	1
VEGFA	-0.003	0.029	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	0.056	0.1	-9999	-0.97	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.022	0.12	-9999	-1.1	7	7
PTPN6	-0.001	0.013	-9999	-0.29	2	2
EPAS1	-0.006	0.069	-9999	-0.73	8	8
mol:L-citrulline	0.073	0.05	-9999	-0.56	5	5
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.071	-9999	-0.95	5	5
VEGFR2 homodimer/VEGFA homodimer	-0.007	0.074	-9999	-0.78	8	8
VEGFR2/3 heterodimer	-0.008	0.091	-9999	-0.92	9	9
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.055	0.078	-9999	-0.95	5	5
VEGFR2 homodimer	0.028	0.091	-9999	-0.95	8	8
FLT1	-0.001	0.025	-9999	-0.8	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.051	0.081	-9999	-0.85	6	6
MAPK1	0.051	0.081	-9999	-0.85	6	6
VEGFA145/NRP2	-0.004	0.04	-9999	-0.66	3	3
VEGFR1/2 heterodimer	-0.007	0.085	-9999	-0.91	8	8
KDR	0.028	0.091	-9999	-0.96	8	8
VEGFA165/NRP1/VEGFR2 homodimer	-0.006	0.081	-9999	-0.98	6	6
SRC	0	0.009	-9999	-0.29	1	1
platelet activating factor biosynthetic process	0.053	0.083	-9999	-0.88	6	6
PI3K	-0.008	0.075	-9999	-0.9	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.007	0.075	-9999	-0.79	8	8
FES	0.049	0.079	-9999	-0.92	5	5
GAB1	-0.005	0.069	-9999	-0.94	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.075	-9999	-0.79	8	8
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.01	0.17	-9999	-0.57	13	13
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.008	0.076	-9999	-0.75	9	9
PI3K/GAB1	0.079	0.076	-9999	-0.72	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.002	0.07	-9999	-0.91	5	5
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.007	0.085	-9999	-0.86	9	9
HSP90AA1	0	0.009	-9999	-10000	0	0
CDC42	0.051	0.075	-9999	-0.92	5	5
actin cytoskeleton reorganization	-0.02	0.084	-9999	-0.74	10	10
PTK2	0.052	0.11	-9999	-1.1	6	6
EDG1	0.042	0.072	-9999	-0.71	8	8
mol:DAG	0.051	0.073	-9999	-0.9	5	5
CaM/Ca2+	-0.006	0.061	-9999	-0.82	5	5
MAP2K3	0.056	0.077	-9999	-0.87	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.005	0.071	-9999	-0.94	5	5
PLCG1	0.051	0.075	-9999	-0.92	5	5
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.007	0.072	-9999	-0.95	5	5
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.025	-9999	-0.8	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.007	0.075	-9999	-0.79	8	8
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.007	0.075	-9999	-0.79	8	8
cell migration	0.078	0.089	-9999	-0.79	6	6
mol:PI-3-4-5-P3	-0.007	0.066	-9999	-0.79	6	6
FYN	-0.002	0.035	-9999	-0.8	2	2
VEGFB/NRP1	-0.006	0.062	-9999	-0.83	5	5
mol:NO	0.073	0.05	-9999	-0.56	5	5
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.057	-9999	-0.77	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.005	0.071	-9999	-0.94	5	5
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.028	0.15	-9999	-0.75	39	39
NOS3	0.075	0.056	-9999	-0.65	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.019	0.1	-9999	-0.55	34	34
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.045	0.11	-9999	-0.99	5	5
PRKCB	0.047	0.1	-9999	-0.9	7	7
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.006	0.067	-9999	-0.71	8	8
VEGFR1/2 heterodimer/VEGFA homodimer	-0.008	0.08	-9999	-0.84	8	8
VEGFA165/NRP2	-0.004	0.04	-9999	-0.66	3	3
MAPKKK cascade	-0.004	0.058	-9999	-0.77	5	5
NRP2	-0.003	0.044	-9999	-0.68	4	4
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	-0.001	0.025	-9999	-0.8	1	1
FAK1/Paxillin	0.056	0.1	-9999	-0.97	6	6
MAP3K13	0.049	0.081	-9999	-0.92	5	5
PDPK1	0.074	0.066	-9999	-0.67	6	6

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0	0.017	-10000	0	-10000	0	0
oxygen homeostasis	0.012	0.012	-10000	0	-10000	0	0
TCEB2	-0.007	0.044	-10000	0	-0.29	25	25
TCEB1	-0.001	0.013	-10000	0	-0.29	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.005	0.037	-10000	0	-0.43	2	2
EPO	0.15	0.15	-10000	0	-0.72	2	2
FIH (dimer)	0.023	0.012	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.3	1	1
SERPINE1	0.16	0.15	-10000	0	-0.69	4	4
FLT1	-0.003	0.079	-10000	0	-1	5	5
ADORA2A	0.14	0.16	-10000	0	-0.67	4	4
germ cell development	0.16	0.15	-10000	0	-0.64	7	7
SLC11A2	0.16	0.15	-10000	0	-0.69	4	4
BHLHE40	0.16	0.15	-10000	0	-0.81	5	5
HIF1AN	0.023	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.015	0.069	-10000	0	-0.44	4	4
ETS1	0.022	0.058	-10000	0	-0.81	5	5
CITED2	0.001	0.01	-10000	0	-10000	0	0
KDR	-0.007	0.11	-10000	0	-1.2	8	8
PGK1	0.16	0.15	-10000	0	-0.69	4	4
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.18	0.16	-10000	0	-0.77	5	5
EPAS1	0.094	0.081	-10000	0	-0.42	4	4
SP1	0.018	0.002	-10000	0	-10000	0	0
ABCG2	0.13	0.25	-10000	0	-0.7	73	73
EFNA1	0.16	0.15	-10000	0	-0.69	4	4
FXN	0.16	0.15	-10000	0	-0.67	4	4
POU5F1	0.16	0.16	-10000	0	-0.67	7	7
neuron apoptosis	-0.18	0.15	0.74	5	-10000	0	5
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0	0.083	-10000	0	-0.28	78	78
EGLN2	0.021	0.026	-10000	0	-0.3	2	2
EGLN1	0.022	0.028	-10000	0	-0.81	1	1
VHL/Elongin B/Elongin C	-0.004	0.022	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.01	-10000	0	-10000	0	0
SLC2A1	0.15	0.15	-10000	0	-0.67	5	5
TWIST1	0.14	0.21	-10000	0	-0.7	38	38
ELK1	0.019	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.008	0.062	-10000	0	-0.61	1	1
VEGFA	0.16	0.15	-10000	0	-0.71	4	4
CREBBP	0	0	-10000	0	-10000	0	0

×

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

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
BAG4	-0.006	0.057	-9999	-0.8	4	4
Caspase 8 (4 units)	-0.009	0.047	-9999	-1	1	1
NEF	-0.006	0.027	-9999	-0.22	9	9
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	0.034	0.084	-9999	-0.81	9	9
CYCS	0.04	0.059	-9999	-0.95	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.026	0.13	-9999	-0.62	37	37
MAP2K7	0.042	0.049	-9999	-0.81	1	1
protein ubiquitination	0.066	0.035	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.003	0.05	-9999	-0.8	4	4
BID	-0.01	0.053	-9999	-1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.034	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.05	-9999	-0.8	4	4
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.004	0.035	-9999	-0.29	15	15
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.034	-9999	-10000	0	0
MAPK8	0.045	0.063	-9999	-0.48	9	9
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.018	-9999	-0.29	4	4
TRAF2	-0.001	0.018	-9999	-0.29	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.012	0.057	-9999	-0.34	20	20
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.032	-9999	-0.37	2	2
CHUK	0.067	0.037	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.005	0.048	-9999	-0.53	7	7
TCRz/NEF	-0.025	0.11	-9999	-0.53	39	39
TNF	-0.018	0.1	-9999	-0.48	38	38
FASLG	-0.007	0.15	-9999	-0.65	39	39
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.014	0.074	-9999	-0.54	18	18
CASP6	-0.004	0.032	-9999	-0.71	1	1
CASP7	0.073	0.077	-9999	-0.62	9	9
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.073	0.077	-9999	-0.62	9	9
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.004	0.042	-9999	-0.61	4	4
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.062	0.04	-9999	-0.36	1	1
APAF-1/Caspase 9	-0.01	0.054	-9999	-0.51	9	9
BCL2	0.036	0.1	-9999	-0.44	42	42

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.028	-9999	-0.91	1	1
VEGFR1 homodimer/NRP1	-0.001	0.028	-9999	-0.92	1	1
mol:DAG	0.038	0.032	-9999	-0.65	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.029	-9999	-0.86	1	1
CaM/Ca2+	-0.001	0.028	-9999	-0.61	2	2
HIF1A	0	0.012	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.005	0.048	-9999	-0.72	1	1
PLCG1	0.038	0.032	-9999	-0.66	2	2
NOS3	0.062	0.032	-9999	-0.56	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.061	0.031	-9999	-0.54	2	2
FLT1	0.029	0.032	-9999	-1	1	1
PGF	-0.001	0.028	-9999	-0.46	3	3
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.048	-9999	-0.79	3	3
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
eNOS/Hsp90	0.065	0.03	-9999	-0.65	1	1
endothelial cell proliferation	0.036	0.089	-9999	-0.65	5	5
mol:Ca2+	0.038	0.032	-9999	-0.64	2	2
MAPK3	0.039	0.083	-9999	-0.44	28	28
MAPK1	0.039	0.083	-9999	-0.44	28	28
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
PLGF homodimer	-0.001	0.028	-9999	-0.46	3	3
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.33	-9999	-0.8	224	224
VEGFA homodimer	-0.003	0.03	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.031	-9999	-0.91	1	1
platelet activating factor biosynthetic process	0.046	0.081	-9999	-1.1	1	1
PI3K	-0.006	0.052	-9999	-0.47	12	12
PRKCA	0.032	0.088	-9999	-0.47	28	28
PRKCB	0.034	0.077	-9999	-0.48	19	19
VEGFR1 homodimer/PLGF homodimer	-0.002	0.033	-9999	-0.72	2	2
VEGFA	-0.003	0.03	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.032	-9999	-0.65	2	2
RASA1	0.039	0.027	-9999	-0.84	1	1
NRP2	-0.003	0.044	-9999	-0.68	4	4
VEGFR1 homodimer	0.029	0.032	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.03	0.19	-9999	-0.64	6	6
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.051	-9999	-0.47	12	12
mol:L-citrulline	0.061	0.031	-9999	-0.54	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.028	-9999	-0.8	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.029	-9999	-0.85	1	1
CD2AP	0	0.009	-9999	-0.29	1	1
PI3K/GAB1	-0.005	0.049	-9999	-0.45	12	12
PDPK1	-0.005	0.048	-9999	-0.74	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.029	-9999	-0.85	1	1
mol:NADP	0.061	0.031	-9999	-0.54	2	2
HSP90AA1	0	0.009	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.002	0.027	-9999	-0.79	1	1
VEGFR1 homodimer/NRP2	-0.002	0.048	-9999	-0.8	3	3

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	-0.001	0.025	-9999	-0.8	1	1
SMAD2	0.014	0.005	-9999	-10000	0	0
SMAD3	0.041	0	-9999	-10000	0	0
SMAD3/SMAD4	0.004	0.016	-9999	-0.29	1	1
SMAD4/Ubc9/PIASy	-0.001	0.016	-9999	-0.53	1	1
SMAD2/SMAD2/SMAD4	-0.01	0.031	-9999	-0.53	1	1
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0.015	-9999	-0.48	1	1
MAP3K1	-0.001	0.025	-9999	-0.8	1	1
TRAP-1/SMAD4	-0.009	0.073	-9999	-0.61	15	15
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.011	0.093	-9999	-0.8	14	14
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-0.29	1	1
KPNA2	-0.03	0.088	-9999	-0.29	107	107
PIAS4	0	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.058	0.077	-9999	-0.52	1	1
CRKL	0.028	0.05	-9999	-0.49	1	1
mol:DAG	-0.007	0.026	-9999	-0.39	1	1
HRAS	-0.006	0.022	-9999	-0.4	1	1
MAPK8	0.01	0.069	-9999	-0.52	8	8
RAP1A	0.028	0.05	-9999	-0.49	1	1
GAB1	0.028	0.05	-9999	-0.49	1	1
MAPK14	0.015	0.051	-9999	-10000	0	0
EPO	-0.036	0.11	-9999	-0.28	171	171
PLCG1	-0.007	0.027	-9999	-0.4	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-0.28	1	1
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.066	-9999	-0.64	6	6
GAB1/SHC/GRB2/SOS1	-0.007	0.022	-9999	-0.42	1	1
EPO/EPOR (dimer)	-0.029	0.065	-9999	-10000	0	0
IRS2	0.009	0.11	-9999	-0.48	42	42
STAT1	0.048	0.057	-9999	-0.51	1	1
STAT5B	-0.004	0.044	-9999	-0.44	4	4
cell proliferation	0.02	0.065	-9999	-0.48	8	8
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.01	0.042	-9999	-0.42	5	5
TEC	0.027	0.057	-9999	-0.49	4	4
SOCS3	-0.005	0.061	-9999	-0.8	6	6
STAT1 (dimer)	0.048	0.056	-9999	-0.5	1	1
JAK2	0.011	0.026	-9999	-0.82	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
EPO/EPOR (dimer)/JAK2	0.054	0.041	-9999	-0.52	1	1
EPO/EPOR	-0.029	0.065	-9999	-10000	0	0
LYN	0.012	0.002	-9999	-10000	0	0
TEC/VAV2	-0.007	0.042	-9999	-0.47	4	4
elevation of cytosolic calcium ion concentration	0.012	0.01	-9999	-0.28	1	1
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.018	0.049	-9999	-10000	0	0
mol:IP3	-0.007	0.026	-9999	-0.39	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.029	0.094	-9999	-0.49	22	22
SH2B3	0.012	0.004	-9999	-10000	0	0
NFKB1	0.015	0.051	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.031	-9999	-0.32	7	7
PTPN6	0.02	0.052	-9999	-0.52	1	1
TEC/VAV2/GRB2	-0.011	0.035	-9999	-0.45	4	4
EPOR	0.012	0.01	-9999	-0.28	1	1
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.008	0.023	-9999	-0.43	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.002	0.036	-9999	-0.63	3	3
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.45	1	1
VAV2	0.028	0.05	-9999	-0.49	1	1
CBL	0.028	0.05	-9999	-0.49	1	1
SHC/Grb2/SOS1	0.005	0.028	-9999	-0.45	1	1
STAT5A	-0.006	0.057	-9999	-0.48	9	9
GRB2	0	0.009	-9999	-0.29	1	1
STAT5 (dimer)	0.057	0.087	-9999	-0.57	5	5
LYN/PLCgamma2	-0.001	0.027	-9999	-0.61	2	2
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.051	-9999	-0.49	1	1
BCL2	0.035	0.2	-9999	-0.98	36	36

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.025	0.3	2	-0.4	1	3
DAPP1	0.036	0.054	-10000	0	-0.59	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.046	0.08	-10000	0	-0.57	10	10
mol:DAG	0.052	0.051	0.21	1	-0.27	7	8
HRAS	-0.002	0.026	-10000	0	-0.28	9	9
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.003	0.026	-10000	0	-0.26	4	4
PLCG2	-0.002	0.036	-10000	0	-0.63	3	3
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	-0.001	0.023	0.27	2	-0.4	2	4
ARF1/GTP	-0.001	0.023	0.28	2	-0.38	2	4
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.025	-10000	0	-0.8	1	1
RAP1A/GTP	-0.001	0.022	0.25	2	-0.39	2	4
ADAP1	-0.003	0.033	-10000	0	-0.42	3	3
ARAP3	-0.001	0.023	0.26	2	-0.4	2	4
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.057	-10000	0	-0.3	35	35
ARHGEF6	-0.012	0.096	-10000	0	-0.8	15	15
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
FYN	-0.002	0.035	-10000	0	-0.8	2	2
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.001	0.026	-10000	0	-0.8	1	1
mol:Ca2+	0.039	0.029	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
ZAP70	-0.03	0.12	-10000	0	-0.8	20	20
mol:IP3	0.047	0.039	-10000	0	-0.21	2	2
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.026	-10000	0	-0.3	2	2
RhoA/GDP	-0.002	0.023	0.28	2	-10000	0	2
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.061	0.035	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
PLEKHA2	0.03	0.008	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.78	2	2
HSP90AA1	0	0.009	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.022	0.3	2	-10000	0	2
RhoA/GTP	-0.001	0.021	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.011	0.058	-10000	0	-0.54	6	6
BLK	-0.041	0.11	-10000	0	-0.3	142	142
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.021	-10000	0	-10000	0	0
HCK	-0.004	0.032	-10000	0	-10000	0	0
CYTH3	-0.002	0.025	-10000	0	-0.42	1	1
CYTH2	-0.001	0.021	-10000	0	-0.37	2	2
KRAS	-0.001	0.013	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.054	-10000	0	-0.56	9	9
SGK1	-0.004	0.056	0.23	2	-0.71	6	8
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.034	-10000	0	-0.28	4	4
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-0.29	1	1
ARF6/GDP	-0.002	0.023	0.29	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.025	0.36	2	-0.39	2	4
ARAP3/RAP1A/GTP	-0.001	0.023	-10000	0	-0.4	2	2
VAV1	-0.003	0.045	-10000	0	-0.6	5	5
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.002	0.02	-10000	0	-0.4	2	2
PLEKHA1	0.03	0.018	-10000	0	-0.53	1	1
Rac1/GDP	-0.003	0.026	-10000	0	-0.3	2	2
LAT	-0.005	0.048	-10000	0	-0.8	2	2
Rac1/GTP	-0.006	0.047	-10000	0	-0.37	15	15
ITK	-0.02	0.087	0.26	1	-0.44	38	39
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.066	0.24	1	-0.39	7	8
LCK	-0.02	0.1	-10000	0	-0.43	49	49
BTK	-0.001	0.022	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.004	0.047	-9999	-0.56	6	6
PDGFB-D/PDGFRB/SLAP	-0.004	0.042	-9999	-0.61	4	4
PDGFB-D/PDGFRB/APS/CBL	-0.009	0.044	-9999	-0.53	4	4
AKT1	-0.011	0.05	-9999	-0.52	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.036	0.054	-9999	-0.6	6	6
PIK3CA	0	0.009	-9999	-0.29	1	1
FGR	-0.003	0.04	-9999	-0.54	5	5
mol:Ca2+	0.033	0.049	-9999	-0.69	4	4
MYC	0.039	0.14	-9999	-0.8	27	27
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.003	0.03	-9999	-0.43	4	4
LRP1/PDGFRB/PDGFB	-0.008	0.07	-9999	-0.6	13	13
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.05	-9999	-0.7	4	4
PTEN	-0.002	0.035	-9999	-0.8	2	2
GRB2	0	0.009	-9999	-0.29	1	1
GRB7	-0.021	0.077	-9999	-0.3	72	72
PDGFB-D/PDGFRB/SHP2	-0.002	0.038	-9999	-0.61	4	4
PDGFB-D/PDGFRB/GRB10	-0.002	0.038	-9999	-0.61	4	4
cell cycle arrest	-0.004	0.041	-9999	-0.61	4	4
HRAS	-0.003	0.027	-9999	-0.29	9	9
HIF1A	0.052	0.059	-9999	-0.45	3	3
GAB1	0.035	0.057	-9999	-0.68	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.04	0.054	-9999	-0.62	4	4
PDGFB-D/PDGFRB	-0.003	0.036	-9999	-0.54	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.038	-9999	-0.61	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.051	-9999	-0.58	6	6
positive regulation of MAPKKK cascade	-0.002	0.038	-9999	-0.61	4	4
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:IP3	0.033	0.051	-9999	-0.71	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.016	0.063	-9999	-0.61	5	5
SHB	-0.001	0.026	-9999	-0.8	1	1
BLK	-0.002	0.051	-9999	-0.59	7	7
PTPN2	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.038	-9999	-0.61	4	4
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.04	0.064	-9999	-0.62	5	5
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.038	-9999	-0.61	4	4
LCK	-0.01	0.083	-9999	-0.64	16	16
PDGFRB	0.008	0.051	-9999	-0.81	4	4
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.035	-9999	-0.52	4	4
ABL1	0.034	0.051	-9999	-0.64	4	4
PDGFB-D/PDGFRB/CBL	0.034	0.062	-9999	-0.8	4	4
PTPN1	-0.002	0.03	-9999	-0.3	1	1
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.005	0.039	-9999	-0.29	19	19
cell proliferation	0.04	0.12	-9999	-0.69	27	27
SLA	-0.003	0.027	-9999	-0.29	9	9
actin cytoskeleton reorganization	-0.003	0.029	-9999	-0.41	2	2
SRC	-0.002	0.034	-9999	-0.51	4	4
PI3K	-0.013	0.056	-9999	-0.59	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.012	0.051	-9999	-0.53	5	5
SH2B2	-0.013	0.061	-9999	-0.29	48	48
PLCgamma1/SPHK1	0.004	0.054	-9999	-0.62	6	6
LYN	-0.002	0.035	-9999	-0.52	4	4
LRP1	-0.009	0.082	-9999	-0.8	11	11
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.002	0.043	-9999	-0.8	3	3
STAT5A	-0.006	0.07	-9999	-0.8	8	8
NCK1-2/p130 Cas	-0.002	0.028	-9999	-0.42	4	4
SPHK1	-0.007	0.052	-9999	-0.34	21	21
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.033	0.051	-9999	-0.71	4	4
PLCG1	0.033	0.052	-9999	-0.73	4	4
NHERF/PDGFRB	-0.015	0.052	-9999	-0.53	4	4
YES1	-0.003	0.039	-9999	-0.53	5	5
cell migration	-0.015	0.052	-9999	-0.52	4	4
SHC/Grb2/SOS1	-0.003	0.028	-9999	-0.42	4	4
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
SLC9A3R1	-0.024	0.08	-9999	-0.29	87	87
NHERF1-2/PDGFRB/PTEN	-0.013	0.049	-9999	-0.48	6	6
FYN	-0.004	0.063	-9999	-0.9	4	4
DOK1	0.005	0.037	-9999	-0.48	4	4
HRAS/GTP	-0.002	0.018	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.046	0.084	-9999	-0.44	27	27
PRKCD	0.03	0.036	-9999	-0.48	4	4
FER	0.024	0.064	-9999	-0.49	15	15
MAPKKK cascade	-0.002	0.028	-9999	-0.42	4	4
RASA1	0.03	0.036	-9999	-0.48	4	4
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.031	-9999	-0.44	4	4
PDGFB-D/PDGFRB/SHB	-0.003	0.043	-9999	-0.61	5	5
chemotaxis	0.034	0.049	-9999	-0.62	4	4
STAT1-3-5/STAT1-3-5	-0.008	0.057	-9999	-0.84	2	2
Bovine Papilomavirus E5/PDGFRB	-0.002	0.039	-9999	-0.62	4	4
PTPRJ	0	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.029	0.037	-9999	-10000	0	0
PLK1	0.007	0.12	-9999	-0.63	7	7
CDKN1B	0.08	0.071	-9999	-0.54	3	3
FOXO3	0.04	0.11	-9999	-0.57	11	11
KAT2B	0.008	0.029	-9999	-0.84	1	1
FOXO1/SIRT1	0.007	0.038	-9999	-0.32	10	10
CAT	0.043	0.12	-9999	-1.1	5	5
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.032	0.04	-9999	-0.36	10	10
MAPK10	-0.04	0.18	-9999	-0.46	162	162
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.063	0.089	-9999	-0.42	1	1
response to oxidative stress	0.005	0.012	-9999	-10000	0	0
FOXO3A/SIRT1	-0.016	0.068	-9999	-0.52	8	8
XPO1	0	0	-9999	-10000	0	0
EP300	0.009	0.005	-9999	-10000	0	0
BCL2L11	0.028	0.019	-9999	-10000	0	0
FOXO1/SKP2	-0.003	0.032	-9999	-0.32	10	10
mol:GDP	0.005	0.012	-9999	-10000	0	0
RAN	0.012	0.001	-9999	-10000	0	0
GADD45A	0.068	0.064	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.069	0.026	-9999	-10000	0	0
MST1	-0.003	0.094	-9999	-0.64	19	19
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.002	0.039	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.033	0.044	-9999	-0.46	8	8
MAPK9	0.036	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.016	-9999	-0.29	3	3
SIRT1	0.002	0.008	-9999	-10000	0	0
SOD2	0.091	0.076	-9999	-10000	0	0
RBL2	0.06	0.082	-9999	-0.55	2	2
RAL/GDP	0.011	0.016	-9999	-10000	0	0
CHUK	0.009	0.012	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.03	0.01	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.004	0.18	-9999	-1.5	13	13
SKP2	0	0	-9999	-10000	0	0
USP7	0.012	0.001	-9999	-10000	0	0
IKBKB	0.008	0.018	-9999	-0.27	2	2
CCNB1	0.033	0.12	-9999	-0.74	3	3
FOXO1-3a-4/beta catenin	-0.009	0.042	-9999	-0.41	6	6
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.032	-9999	-0.32	10	10
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.004	0.063	-9999	-0.81	6	6
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.068	0.079	-9999	-10000	0	0
SFN	-0.015	0.097	-9999	-0.5	31	31
CDK2	0.002	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.027	0.05	-9999	-10000	0	0
CREBBP	0.002	0.005	-9999	-10000	0	0
FBXO32	0.042	0.13	-9999	-1.2	6	6
BCL6	0.055	0.12	-9999	-1.2	6	6
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.008	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.007	0.059	-9999	-0.53	13	13
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.025	-9999	-10000	0	0
NFKBIA	0.024	0.035	-9999	-0.27	13	13
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0.017	0	-9999	-10000	0	0
REL	-0.01	0.089	-9999	-0.8	13	13
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.009	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0.006	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.035	-9999	-0.27	13	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.024	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.06	-9999	-0.61	10	10
NF kappa B1 p50/RelA	-0.004	0.03	-9999	-0.27	13	13
IKBKB	-0.001	0.013	-9999	-0.29	2	2
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-0.29	1	1
I kappa B alpha/PIK3R1	-0.008	0.051	-9999	-0.45	10	10
cell death	-0.003	0.023	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.007	0.059	-9999	-0.53	13	13
LCK	-0.02	0.1	-9999	-0.43	49	49
BCL3	-0.001	0.013	-9999	-0.29	2	2

×

Circadian rhythm 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
chromatin modification	-0.004	0.019	-9999	-10000	0	0
CLOCK	0.005	0.087	-9999	-0.8	12	12
TIMELESS/CRY2	-0.002	0.011	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.011	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.041	0.017	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.04	0.02	-9999	-10000	0	0
NPAS2	0.008	0.064	-9999	-0.63	9	9
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.014	0.003	-9999	-10000	0	0
CHEK1	-0.007	0.045	-9999	-0.29	26	26
mol:HEME	0.014	0.003	-9999	-10000	0	0
PER1	-0.015	0.11	-9999	-0.8	20	20
BMAL/CLOCK/NPAS2	-0.009	0.068	-9999	-0.52	18	18
BMAL1/CLOCK	0.041	0.055	-9999	-0.4	11	11
S phase of mitotic cell cycle	-0.004	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.004	0.019	-9999	-10000	0	0
mol:NADPH	0.014	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.01	0.064	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.001	0.018	-9999	-0.29	4	4

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.005	0.058	-9999	-0.49	14	14
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.047	-9999	-0.41	14	14
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.024	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.024	-9999	-10000	0	0
YY1/LSF	-0.001	0.018	-9999	-0.4	2	2
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.006	0.042	-9999	-0.36	14	14
I kappa B alpha/HDAC1	-0.004	0.028	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.005	0.037	-9999	-0.32	14	14
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.006	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.033	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.026	0.13	-9999	-0.63	42	42
GATA1	-0.005	0.037	-9999	-0.29	17	17
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.008	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	-0.001	0.025	-9999	-0.8	1	1
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.005	0.033	-9999	-10000	0	0
KAT2B	-0.001	0.025	-9999	-0.8	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.008	-9999	-10000	0	0
SIN3 complex	0	0.007	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.025	-9999	-0.8	1	1
YY1/HDAC3	-0.004	0.026	-9999	-10000	0	0
YY1/HDAC2	0	0.009	-9999	-0.3	1	1
YY1/HDAC1	0	0.009	-9999	-0.3	1	1
NuRD/MBD2 Complex (MeCP1)	0	0.006	-9999	-10000	0	0
PPARG	-0.094	0.17	-9999	-0.38	252	252
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.028	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-9999	-0.29	2	2
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.005	0.033	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0.011	-9999	-0.35	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0.009	-9999	-0.29	1	1
STAT3	0.025	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.017	-9999	-0.47	1	1
YY1/SAP30/HDAC1	-0.001	0.011	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.033	-9999	-10000	0	0
histone deacetylation	0.046	0.008	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.025	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.019	0.083	-9999	-0.48	28	28
GATA1/HDAC1	-0.003	0.023	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.032	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.076	-9999	-0.61	14	14
SIN3/HDAC complex/Mad/Max	0	0.006	-9999	-10000	0	0
NuRD Complex	0	0.007	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.023	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.018	-9999	-0.48	1	1
GATA1/Fog1	-0.004	0.028	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.018	0.1	-9999	-0.48	38	38
negative regulation of cell growth	0.046	0.009	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.05	-9999	-0.43	14	14
SIN3/HDAC complex/NCoR1	0	0.01	-9999	-0.26	1	1
TFCP2	-0.001	0.025	-9999	-0.8	1	1
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0.009	-9999	-0.29	1	1
MBD2	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.077	0.036	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.007	0.039	-9999	-0.49	2	2
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-0.29	2	2
RIPK2	-0.001	0.02	-9999	-0.29	5	5
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.003	0.047	-9999	-10000	0	0
NEMO/A20/RIP2	-0.001	0.02	-9999	-0.29	5	5
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.008	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.009	0.054	-9999	-0.31	31	31
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.013	0.076	-9999	-0.61	14	14
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.021	0.13	-9999	-0.77	29	29
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.018	0.1	-9999	-0.48	38	38
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0	0.008	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.061	-9999	-0.38	27	27

×

a4b1 and a4b7 Integrin signaling

Figure S122. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S122. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.009	0.058	-9999	-0.8	2	2
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.029	0.044	-10000	0	-10000	0	0
regulation of axonogenesis	0.004	0.03	0.32	9	-10000	0	9
myoblast fusion	0.007	0.025	-10000	0	-10000	0	0
mol:GTP	-0.005	0.015	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.029	-10000	0	-10000	0	0
ARF1/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GM1	0.006	0.014	-10000	0	-10000	0	0
mol:Choline	0.021	0.052	-10000	0	-0.52	9	9
lamellipodium assembly	-0.004	0.031	-10000	0	-10000	0	0
MAPK3	0.021	0.024	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.029	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.007	0.025	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.024	-10000	0	-10000	0	0
ARF6	0.007	0.007	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
TIAM1	0.011	0.019	-10000	0	-0.29	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.024	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.021	-10000	0	-10000	0	0
KALRN	-0.01	0.065	-10000	0	-0.48	18	18
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.021	-10000	0	-10000	0	0
NME1	-0.003	0.065	-10000	0	-0.29	51	51
Rac1/GDP	-0.006	0.021	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.015	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.031	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.015	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.015	-10000	0	-10000	0	0
RhoA/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.029	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.011	0.058	-10000	0	-0.59	9	9
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.031	-10000	0	-10000	0	0
ruffle organization	-0.004	0.03	-10000	0	-0.32	9	9
regulation of epithelial cell migration	-0.005	0.015	-10000	0	-10000	0	0
PLD2	0.017	0.013	-10000	0	-10000	0	0
PIP5K1A	-0.004	0.03	-10000	0	-0.32	9	9
mol:Phosphatidic acid	0.021	0.052	-10000	0	-0.52	9	9
Rac1/GTP	-0.004	0.031	-10000	0	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.011	0.036	-9999	-0.42	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.007	0.028	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.023	-9999	-0.53	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.006	0.04	-9999	-0.34	2	2
CaM/Ca2+	0.009	0.032	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.012	0.036	-9999	-0.41	1	1
AKT1	-0.01	0.043	-9999	-0.46	2	2
MAP2K1	0.04	0.044	-9999	-10000	0	0
MAP3K11	0.03	0.043	-9999	-10000	0	0
IFNGR1	0.001	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.097	-9999	-0.41	24	24
Rap1/GTP	-0.004	0.016	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.012	0.037	-9999	-0.44	2	2
CEBPB	0.075	0.04	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.008	0.056	-9999	-1.2	1	1
STAT1	-0.011	0.036	-9999	-0.4	1	1
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.039	0.098	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
STAT1 (dimer)/PIAS1	-0.01	0.032	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	0.01	0.035	-9999	-0.42	2	2
MAPK3	0.054	0.041	-9999	-10000	0	0
STAT1 (dimer)	-0.007	0.054	-9999	-0.49	2	2
MAPK1	0.054	0.041	-9999	-10000	0	0
JAK2	0	0.025	-9999	-0.8	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
JAK1	0	0.025	-9999	-0.8	1	1
CAMK2D	-0.002	0.043	-9999	-0.8	3	3
DAPK1	0.069	0.033	-9999	-10000	0	0
SMAD7	0.05	0.038	-9999	-0.18	1	1
CBL/CRKL/C3G	-0.007	0.022	-9999	-10000	0	0
PI3K	0.004	0.052	-9999	-0.5	2	2
IFNG	-0.039	0.098	-9999	-10000	0	0
apoptosis	0.053	0.029	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.009	0.049	-9999	-0.29	31	31
CAMK2B	-0.07	0.21	-9999	-0.6	121	121
FRAP1	0.038	0.055	-9999	-0.43	2	2
PRKCD	-0.01	0.044	-9999	-0.46	2	2
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.006	0.04	-9999	-0.34	2	2
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.047	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.01	0.033	-9999	-10000	0	0
SOCS1	0	0.05	-9999	-1.5	1	1
mol:GDP	-0.007	0.021	-9999	-10000	0	0
CASP1	0.049	0.046	-9999	-0.36	5	5
PTGES2	0	0.009	-9999	-0.29	1	1
IRF9	0.057	0.019	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.047	-9999	-0.43	6	6
RAP1/GDP	-0.004	0.016	-9999	-10000	0	0
CBL	-0.01	0.028	-9999	-10000	0	0
MAP3K1	0.03	0.045	-9999	-0.42	2	2
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.006	0.04	-9999	-0.34	2	2
PTPN11	-0.011	0.032	-9999	-0.42	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.045	0.047	-10000	0	-0.55	1	1
BAG4	-0.006	0.057	-10000	0	-0.8	4	4
BAD	0.032	0.018	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.08	-10000	0	-0.8	9	9
BAX	0.031	0.02	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.013	-10000	0	-0.1	2	2
IKBKB	0.051	0.046	-10000	0	-0.52	1	1
MAP2K2	0.044	0.025	-10000	0	-0.47	1	1
MAP2K1	0.044	0.025	-10000	0	-0.47	1	1
SMPD1	0.021	0.013	-10000	0	-0.11	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.05	0.05	-10000	0	-0.45	3	3
MAP2K4	0.038	0.026	-10000	0	-0.39	2	2
protein ubiquitination	0.053	0.046	-10000	0	-0.52	1	1
EnzymeConsortium:2.7.1.37	0.049	0.027	-10000	0	-0.5	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.039	0.025	-10000	0	-0.5	1	1
CRADD	0	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.018	-10000	0	-0.15	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.023	-10000	0	-0.41	1	1
TRADD	0	0	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.046	0.024	-10000	0	-0.46	1	1
MAPK1	0.046	0.024	-10000	0	-0.46	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.043	0.051	-10000	0	-0.47	3	3
KSR1	0.032	0.025	-10000	0	-0.53	1	1
MAPK8	0.041	0.048	-10000	0	-0.43	9	9
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.051	0.045	-10000	0	-0.52	1	1
TNF R/SODD	-0.004	0.042	-10000	0	-0.61	4	4
TNF	-0.018	0.1	-10000	0	-0.8	14	14
CYCS	0.037	0.027	0.15	31	-10000	0	31
IKBKG	0.051	0.045	-10000	0	-0.52	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.038	0.05	-10000	0	-0.59	1	1
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.027	0.15	31	-10000	0	31
TNF/TNF R/SODD	-0.014	0.074	-10000	0	-0.54	18	18
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.027	0.013	-10000	0	-10000	0	0
NSMAF	0.045	0.047	-10000	0	-0.55	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.51	9	9
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	-0.001	0.013	-9999	-0.29	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.12	0.15	-9999	-0.35	11	11
YWHAZ	-0.001	0.016	-9999	-0.29	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.019	0.048	-9999	-0.62	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.003	0.028	-9999	-10000	0	0
PRKCI	0	0.009	-9999	-0.29	1	1
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.032	0	-9999	-10000	0	0
PRKCZ	-0.001	0.025	-9999	-0.8	1	1
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.004	0.031	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.13	0.16	-9999	-0.39	11	11
STX4	0	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.015	0.097	-9999	-0.5	31	31
LNPEP	-0.006	0.07	-9999	-0.8	8	8
YWHAE	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.014	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.033	-9999	-0.48	2	2
lamellipodium assembly	-0.004	0.046	-9999	-0.46	10	10
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.06	-9999	-0.61	10	10
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
cell adhesion	-0.001	0.01	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.011	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.009	0.058	-9999	-0.8	2	2
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.007	0.049	-9999	-0.45	12	12
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.011	0.089	-9999	-0.63	18	18
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.012	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.001	0.012	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	-0.004	0.051	-9999	-0.52	10	10

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.024	0.078	-9999	-9999
TP53	-0.008	0.02	-9999	-9999
Senescence	-0.008	0.02	-9999	-9999
Apoptosis	-0.008	0.02	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.017	0.04	-9999	-9999
MDM4	0	0	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.012	-9999	-0.37	1	1
MDM2/SUMO1	0	0.007	-9999	-10000	0	0
HDAC4	-0.001	0.025	-9999	-0.8	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.029	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0.014	-9999	-0.44	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0	0.007	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-0.29	4	4
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

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	-0.001	0.009	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	-0.001	0.02	-9999	-0.29	5	5
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.003	-9999	-10000	0	0
CD4	0	0	-9999	-10000	0	0
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.01	0.016	-9999	-0.2	6	6
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.007	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.009	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.009	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.004	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-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	0.001	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0.016	-9999	-0.2	6	6
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0.016	-9999	-0.2	6	6
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0	0	-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	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.01	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.018	-9999	-10000	0	0
RELB	-0.003	0.028	-9999	-10000	0	0
NFKB2	0	0.009	-9999	-0.29	1	1
NF kappa B2 p52/RelB	-0.002	0.015	-9999	-10000	0	0
regulation of B cell activation	-0.002	0.015	-9999	-10000	0	0

pid_entity	TCGA.V7.A7HQ	TCGA.S3.A6ZH	TCGA.S3.A6ZG	TCGA.S3.A6ZF
109_MAP3K5	-0.27	-0.27	0.054	0.054
47_PPARGC1A	0	-0.8	0	-0.8
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	-0.8	-0.8	-0.8	0
131_RELN/VLDLR	-0.48	-0.48	-0.48	-0.48
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	-0.43	-0.074	-0.074	-0.072
84_STAT5A	-0.43	-0.074	-0.074	-0.072