PARADIGM pathway analysis of mRNASeq expression and copy number data - Kidney Renal Clear Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	248
HIF-1-alpha transcription factor network	178
TCGA08_retinoblastoma	171
TCGA08_p53	158
EGFR-dependent Endothelin signaling events	142
TCR signaling in naïve CD8+ T cells	140
PDGFR-alpha signaling pathway	115
FOXA2 and FOXA3 transcription factor networks	114
Syndecan-4-mediated signaling events	94
Aurora B signaling	93

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Nephrin/Neph1 signaling in the kidney podocyte	0.4653	248	8465	34	-0.51	0.03	1000	-1000	-0.052	-1000
HIF-1-alpha transcription factor network	0.3340	178	13558	76	-1.1	0.045	1000	-1000	-0.16	-1000
TCGA08_retinoblastoma	0.3208	171	1375	8	-0.58	0.16	1000	-1000	-0.007	-1000
TCGA08_p53	0.2964	158	1111	7	-0.42	0.22	1000	-1000	-0.015	-1000
EGFR-dependent Endothelin signaling events	0.2664	142	2989	21	-0.57	0.043	1000	-1000	-0.058	-1000
TCR signaling in naïve CD8+ T cells	0.2627	140	13059	93	-0.44	0.2	1000	-1000	-0.076	-1000
PDGFR-alpha signaling pathway	0.2158	115	5067	44	-0.22	0.037	1000	-1000	-0.056	-1000
FOXA2 and FOXA3 transcription factor networks	0.2139	114	5280	46	-1.1	0.036	1000	-1000	-0.13	-1000
Syndecan-4-mediated signaling events	0.1764	94	6336	67	-0.43	0.089	1000	-1000	-0.067	-1000
Aurora B signaling	0.1745	93	6262	67	-0.26	0.042	1000	-1000	-0.057	-1000
IL12-mediated signaling events	0.1689	90	7883	87	-0.44	0.11	1000	-1000	-0.13	-1000
Glypican 1 network	0.1595	85	4095	48	-0.4	0.046	1000	-1000	-0.039	-1000
FOXM1 transcription factor network	0.1482	79	4039	51	-0.56	0.031	1000	-1000	-0.13	-1000
amb2 Integrin signaling	0.1388	74	6085	82	-0.45	0.038	1000	-1000	-0.054	-1000
BMP receptor signaling	0.1332	71	5798	81	-0.52	0.054	1000	-1000	-0.084	-1000
Aurora C signaling	0.1295	69	486	7	-0.26	0.027	1000	-1000	-0.019	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1220	65	2158	33	-0.57	0.056	1000	-1000	-0.056	-1000
Glypican 2 network	0.1182	63	253	4	-0.041	-1000	1000	-1000	0.001	-1000
IL4-mediated signaling events	0.1144	61	5581	91	-0.79	0.49	1000	-1000	-0.12	-1000
Caspase cascade in apoptosis	0.1051	56	4189	74	-0.29	0.093	1000	-1000	-0.047	-1000
Syndecan-1-mediated signaling events	0.0994	53	1824	34	-0.25	0.03	1000	-1000	-0.063	-1000
JNK signaling in the CD4+ TCR pathway	0.0957	51	869	17	-0.22	0.03	1000	-1000	-0.052	-1000
Fc-epsilon receptor I signaling in mast cells	0.0901	48	4685	97	-0.23	0.04	1000	-1000	-0.088	-1000
HIF-2-alpha transcription factor network	0.0769	41	1799	43	-0.53	0.25	1000	-1000	-0.072	-1000
Effects of Botulinum toxin	0.0732	39	1021	26	-0.23	0.04	1000	-1000	-0.036	-1000
Arf6 signaling events	0.0713	38	2407	62	-0.57	0.065	1000	-1000	-0.05	-1000
Calcium signaling in the CD4+ TCR pathway	0.0694	37	1151	31	-0.37	0.029	1000	-1000	-0.071	-1000
Coregulation of Androgen receptor activity	0.0675	36	2788	76	-0.86	0.055	1000	-1000	-0.031	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0675	36	1953	54	-0.44	0.041	1000	-1000	-0.08	-1000
Signaling events mediated by the Hedgehog family	0.0657	35	1852	52	-0.28	0.068	1000	-1000	-0.064	-1000
Reelin signaling pathway	0.0657	35	1997	56	-0.17	0.079	1000	-1000	-0.066	-1000
IL27-mediated signaling events	0.0638	34	1742	51	-0.6	0.059	1000	-1000	-0.069	-1000
Ephrin A reverse signaling	0.0619	33	232	7	-0.026	0.012	1000	-1000	-0.019	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0619	33	2266	68	-0.33	0.059	1000	-1000	-0.11	-1000
PLK1 signaling events	0.0600	32	2770	85	-0.18	0.042	1000	-1000	-0.038	-1000
LPA4-mediated signaling events	0.0582	31	383	12	-0.1	0.011	1000	-1000	-0.028	-1000
IL2 signaling events mediated by STAT5	0.0582	31	702	22	-0.29	0.036	1000	-1000	-0.066	-1000
p75(NTR)-mediated signaling	0.0544	29	3674	125	-0.3	0.079	1000	-1000	-0.11	-1000
S1P1 pathway	0.0544	29	1052	36	-0.25	0.029	1000	-1000	-0.062	-1000
Integrins in angiogenesis	0.0507	27	2284	84	-0.27	0.067	1000	-1000	-0.068	-1000
IL23-mediated signaling events	0.0488	26	1560	60	-0.26	0.029	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0469	25	2482	99	-0.22	0.057	1000	-1000	-0.096	-1000
IL2 signaling events mediated by PI3K	0.0450	24	1444	58	-0.29	0.047	1000	-1000	-0.055	-1000
VEGFR1 specific signals	0.0450	24	1370	56	-0.32	0.03	1000	-1000	-0.081	-1000
Signaling events mediated by PTP1B	0.0432	23	1764	76	-0.57	0.065	1000	-1000	-0.057	-1000
Glucocorticoid receptor regulatory network	0.0432	23	2706	114	-0.34	0.15	1000	-1000	-0.081	-1000
Wnt signaling	0.0432	23	162	7	-0.042	0.028	1000	-1000	-0.034	-1000
Ceramide signaling pathway	0.0413	22	1723	76	-0.57	0.21	1000	-1000	-0.059	-1000
Regulation of Telomerase	0.0413	22	2274	102	-0.57	0.062	1000	-1000	-0.086	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0413	22	1960	88	-0.2	0.046	1000	-1000	-0.086	-1000
FoxO family signaling	0.0394	21	1357	64	-0.56	0.095	1000	-1000	-0.057	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0394	21	983	45	-0.36	0.078	1000	-1000	-0.083	-1000
Visual signal transduction: Rods	0.0394	21	1142	52	-0.16	0.04	1000	-1000	-0.056	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0394	21	1654	78	-0.25	0.046	1000	-1000	-0.066	-1000
Noncanonical Wnt signaling pathway	0.0356	19	509	26	-0.098	0.029	1000	-1000	-0.071	-1000
Syndecan-2-mediated signaling events	0.0356	19	1320	69	-0.45	0.063	1000	-1000	-0.055	-1000
EPO signaling pathway	0.0338	18	1040	55	-0.17	0.036	1000	-1000	-0.078	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0338	18	2198	120	-0.11	0.081	1000	-1000	-0.076	-1000
Endothelins	0.0319	17	1653	96	-0.33	0.048	1000	-1000	-0.076	-1000
IL6-mediated signaling events	0.0319	17	1348	75	-0.22	0.06	1000	-1000	-0.058	-1000
Regulation of nuclear SMAD2/3 signaling	0.0300	16	2259	136	-0.3	0.1	1000	-1000	-0.06	-1000
Presenilin action in Notch and Wnt signaling	0.0300	16	1004	61	-0.14	0.084	1000	-1000	-0.063	-1000
LPA receptor mediated events	0.0300	16	1657	102	-0.25	0.052	1000	-1000	-0.079	-1000
Thromboxane A2 receptor signaling	0.0281	15	1630	105	-0.57	0.047	1000	-1000	-0.065	-1000
Aurora A signaling	0.0281	15	904	60	-0.15	0.063	1000	-1000	-0.041	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0281	15	1141	74	-0.57	0.11	1000	-1000	-0.093	-1000
Class I PI3K signaling events	0.0281	15	1128	73	-0.31	0.08	1000	-1000	-0.062	-1000
IFN-gamma pathway	0.0263	14	969	68	-0.24	0.043	1000	-1000	-0.091	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0263	14	518	37	-0.17	0.058	1000	-1000	-0.048	-1000
Canonical Wnt signaling pathway	0.0263	14	723	51	-0.14	0.098	1000	-1000	-0.071	-1000
S1P5 pathway	0.0244	13	223	17	-0.079	0.029	1000	-1000	-0.037	-1000
Nongenotropic Androgen signaling	0.0244	13	715	52	-0.12	0.045	1000	-1000	-0.049	-1000
Plasma membrane estrogen receptor signaling	0.0244	13	1135	86	-0.15	0.053	1000	-1000	-0.093	-1000
Regulation of Androgen receptor activity	0.0244	13	962	70	-0.91	0.054	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0225	12	348	28	-0.079	0.048	1000	-1000	-0.039	-1000
PLK2 and PLK4 events	0.0225	12	38	3	0.006	0.026	1000	-1000	-0.025	-1000
Signaling events regulated by Ret tyrosine kinase	0.0225	12	1030	82	-0.03	0.03	1000	-1000	-0.097	-1000
S1P3 pathway	0.0225	12	528	42	-0.24	0.051	1000	-1000	-0.058	-1000
ErbB4 signaling events	0.0206	11	826	69	-0.16	0.095	1000	-1000	-0.063	-1000
FAS signaling pathway (CD95)	0.0206	11	555	47	-0.28	0.049	1000	-1000	-0.055	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0206	11	1402	125	-0.24	0.044	1000	-1000	-0.079	-1000
TCGA08_rtk_signaling	0.0206	11	291	26	-0.22	0.057	1000	-1000	-0.029	-1000
S1P4 pathway	0.0206	11	294	25	-0.079	0.039	1000	-1000	-0.045	-1000
E-cadherin signaling events	0.0206	11	57	5	0.007	0.026	1000	-1000	-0.013	-1000
Syndecan-3-mediated signaling events	0.0188	10	363	35	-0.011	0.079	1000	-1000	-0.038	-1000
a4b1 and a4b7 Integrin signaling	0.0169	9	48	5	0.01	0.029	1000	-1000	-0.004	-1000
ceramide signaling pathway	0.0169	9	467	49	-0.064	0.045	1000	-1000	-0.061	-1000
Visual signal transduction: Cones	0.0150	8	318	38	-0.013	0.044	1000	-1000	-0.029	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0131	7	663	85	-0.038	0.082	1000	-1000	-0.069	-1000
Ephrin B reverse signaling	0.0131	7	375	48	-0.047	0.052	1000	-1000	-0.042	-1000
Signaling events mediated by PRL	0.0131	7	248	34	-0.044	0.063	1000	-1000	-0.059	-1000
Class IB PI3K non-lipid kinase events	0.0131	7	21	3	-0.021	0.021	1000	-1000	-0.005	-1000
Canonical NF-kappaB pathway	0.0113	6	267	39	-0.11	0.057	1000	-1000	-0.059	-1000
Insulin-mediated glucose transport	0.0113	6	192	32	-0.041	0.057	1000	-1000	-0.037	-1000
mTOR signaling pathway	0.0113	6	324	53	-0.064	0.054	1000	-1000	-0.059	-1000
IL1-mediated signaling events	0.0113	6	376	62	-0.041	0.065	1000	-1000	-0.075	-1000
E-cadherin signaling in the nascent adherens junction	0.0113	6	493	76	-0.031	0.05	1000	-1000	-0.091	-1000
Ras signaling in the CD4+ TCR pathway	0.0113	6	106	17	-0.01	0.054	1000	-1000	-0.038	-1000
ErbB2/ErbB3 signaling events	0.0094	5	339	65	-0.12	0.042	1000	-1000	-0.062	-1000
Cellular roles of Anthrax toxin	0.0094	5	220	39	-0.01	0.039	1000	-1000	-0.024	-1000
Signaling events mediated by HDAC Class III	0.0094	5	232	40	-0.054	0.054	1000	-1000	-0.023	-1000
Signaling mediated by p38-gamma and p38-delta	0.0094	5	75	15	0	0.03	1000	-1000	-0.031	-1000
Signaling mediated by p38-alpha and p38-beta	0.0094	5	246	44	-0.042	0.053	1000	-1000	-0.051	-1000
EPHB forward signaling	0.0094	5	437	85	-0.054	0.073	1000	-1000	-0.1	-1000
PDGFR-beta signaling pathway	0.0094	5	511	97	-0.019	0.087	1000	-1000	-0.087	-1000
p38 MAPK signaling pathway	0.0094	5	253	44	-0.063	0.057	1000	-1000	-0.048	-1000
Regulation of p38-alpha and p38-beta	0.0075	4	263	54	-0.022	0.067	1000	-1000	-0.061	-1000
Insulin Pathway	0.0075	4	310	74	-0.032	0.08	1000	-1000	-0.085	-1000
E-cadherin signaling in keratinocytes	0.0075	4	212	43	-0.22	0.042	1000	-1000	-0.064	-1000
BARD1 signaling events	0.0056	3	207	57	-0.095	0.076	1000	-1000	-0.071	-1000
Osteopontin-mediated events	0.0056	3	120	38	0	0.085	1000	-1000	-0.062	-1000
Hedgehog signaling events mediated by Gli proteins	0.0056	3	227	65	-0.005	0.1	1000	-1000	-0.067	-1000
Class I PI3K signaling events mediated by Akt	0.0056	3	234	68	-0.041	0.055	1000	-1000	-0.05	-1000
Nectin adhesion pathway	0.0056	3	192	63	0	0.057	1000	-1000	-0.067	-1000
Arf6 trafficking events	0.0056	3	252	71	-0.12	0.063	1000	-1000	-0.064	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0038	2	127	52	-0.015	0.1	1000	-1000	-0.054	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0038	2	223	83	-0.041	0.074	1000	-1000	-0.063	-1000
Retinoic acid receptors-mediated signaling	0.0038	2	119	58	-0.015	0.053	1000	-1000	-0.063	-1000
Paxillin-dependent events mediated by a4b1	0.0038	2	75	36	-0.052	0.054	1000	-1000	-0.061	-1000
Atypical NF-kappaB pathway	0.0038	2	62	31	0	0.037	1000	-1000	-0.044	-1000
IGF1 pathway	0.0038	2	126	57	-0.048	0.078	1000	-1000	-0.09	-1000
Signaling events mediated by HDAC Class II	0.0019	1	116	75	-0.041	0.062	1000	-1000	-0.044	-1000
Circadian rhythm pathway	0.0019	1	25	22	-0.014	0.069	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class I	0.0019	1	183	104	-0.057	0.076	1000	-1000	-0.059	-1000
Arf1 pathway	0.0019	1	80	54	0	0.049	1000	-1000	-0.031	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	19	23	-0.027	0.056	1000	-1000	-0.042	-1000
Arf6 downstream pathway	0.0000	0	40	43	-0.047	0.048	1000	-1000	-0.045	-1000
TRAIL signaling pathway	0.0000	0	32	48	0	0.072	1000	-1000	-0.057	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	0	0.07	1000	-1000	-0.057	-1000
Rapid glucocorticoid signaling	0.0000	0	12	20	-0.008	0.036	1000	-1000	-0.012	-1000
Alternative NF-kappaB pathway	0.0000	0	10	13	0	0.062	1000	-1000	-0.015	-1000
Total	NA	3822	202347	7203	-30	-990	131000	-131000	-7.9	-131000

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.4	0.23	0.52	392	-10000	0	392
KIRREL	-0.06	0.087	-10000	0	-0.63	9	9
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.4	0.23	-10000	0	-0.52	392	392
PLCG1	0.029	0.006	-10000	0	-10000	0	0
ARRB2	0.028	0.032	-10000	0	-0.71	1	1
WASL	0.027	0.009	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.42	0.28	-10000	0	-0.54	413	413
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.34	0.24	-10000	0	-0.46	369	369
FYN	-0.4	0.25	0.26	1	-0.5	417	418
mol:Ca2+	-0.41	0.28	-10000	0	-0.53	406	406
mol:DAG	-0.41	0.28	-10000	0	-0.53	406	406
NPHS2	-0.34	0.33	-10000	0	-0.69	241	241
mol:IP3	-0.41	0.28	-10000	0	-0.53	406	406
regulation of endocytosis	-0.37	0.25	-10000	0	-0.49	394	394
Nephrin/NEPH1/podocin/Cholesterol	-0.42	0.28	-10000	0	-0.54	417	417
establishment of cell polarity	-0.4	0.23	-10000	0	-0.52	392	392
Nephrin/NEPH1/podocin/NCK1-2	-0.38	0.27	-10000	0	-0.65	216	216
Nephrin/NEPH1/beta Arrestin2	-0.38	0.25	-10000	0	-0.49	394	394
NPHS1	-0.51	0.28	-10000	0	-0.67	404	404
Nephrin/NEPH1/podocin	-0.4	0.26	-10000	0	-0.51	417	417
TJP1	0.03	0.003	-10000	0	-10000	0	0
NCK1	0.027	0.03	-10000	0	-0.64	1	1
NCK2	0.029	0.006	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.41	0.28	-10000	0	-0.54	406	406
CD2AP	0.029	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.41	0.28	-10000	0	-0.54	411	411
GRB2	0.029	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.39	0.26	0.28	1	-0.5	408	409
cytoskeleton organization	-0.43	0.28	-10000	0	-0.58	369	369
Nephrin/NEPH1	-0.29	0.17	-10000	0	-0.38	392	392
Nephrin/NEPH1/ZO-1	-0.32	0.2	-10000	0	-0.43	390	390

×

HIF-1-alpha transcription factor network

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
PKM2	-0.88	0.48	-10000	0	-1.2	302	302
HDAC7	0.027	0.01	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.63	0.31	-10000	0	-0.92	206	206
SMAD4	0.03	0.005	-10000	0	-10000	0	0
ID2	-0.87	0.48	-10000	0	-1.3	260	260
AP1	0.029	0.077	-10000	0	-0.46	12	12
ABCG2	-0.87	0.48	-10000	0	-1.3	273	273
HIF1A	-0.11	0.074	-10000	0	-0.77	2	2
TFF3	-0.88	0.49	-10000	0	-1.3	273	273
GATA2	0.014	0.097	-10000	0	-0.61	12	12
AKT1	-0.1	0.061	-10000	0	-10000	0	0
response to hypoxia	-0.12	0.061	-10000	0	-0.37	6	6
MCL1	-0.87	0.48	-10000	0	-1.2	275	275
NDRG1	-0.87	0.48	-10000	0	-1.3	272	272
SERPINE1	-0.89	0.51	-10000	0	-1.3	275	275
FECH	-0.87	0.48	-10000	0	-1.3	274	274
FURIN	-0.87	0.48	-10000	0	-1.3	271	271
NCOA2	0.012	0.091	-10000	0	-0.64	10	10
EP300	-0.11	0.077	-10000	0	-0.43	5	5
HMOX1	-0.88	0.49	-10000	0	-1.3	275	275
BHLHE40	-0.87	0.48	-10000	0	-1.3	265	265
BHLHE41	-0.93	0.52	-10000	0	-1.3	281	281
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.1	0.083	-10000	0	-0.54	2	2
ENG	-0.085	0.087	0.43	1	-0.49	2	3
JUN	0.029	0.007	-10000	0	-10000	0	0
RORA	-0.87	0.48	-10000	0	-1.3	263	263
ABCB1	-0.27	0.39	-10000	0	-1.3	66	66
TFRC	-0.87	0.48	-10000	0	-1.3	273	273
CXCR4	-0.95	0.53	-10000	0	-1.3	298	298
TF	-0.92	0.52	-10000	0	-1.3	279	279
CITED2	-0.87	0.48	-10000	0	-1.3	269	269
HIF1A/ARNT	-1.1	0.72	-10000	0	-1.5	306	306
LDHA	-0.082	0.12	-10000	0	-0.78	12	12
ETS1	-0.87	0.48	-10000	0	-1.3	272	272
PGK1	-0.87	0.48	-10000	0	-1.3	270	270
NOS2	-0.88	0.48	-10000	0	-1.3	266	266
ITGB2	-0.91	0.51	-10000	0	-1.3	288	288
ALDOA	-0.87	0.48	-10000	0	-1.3	271	271
Cbp/p300/CITED2	-0.87	0.48	-10000	0	-1.3	263	263
FOS	0.013	0.099	-10000	0	-0.63	12	12
HK2	-1	0.52	-10000	0	-1.4	340	340
SP1	0.023	0.043	-10000	0	-10000	0	0
GCK	-0.17	0.16	-10000	0	-0.95	9	9
HK1	-0.87	0.48	-10000	0	-1.3	265	265
NPM1	-0.84	0.49	-10000	0	-1.2	262	262
EGLN1	-0.87	0.48	-10000	0	-1.3	271	271
CREB1	0.036	0.01	-10000	0	-10000	0	0
PGM1	-0.87	0.48	-10000	0	-1.3	271	271
SMAD3	0.031	0.003	-10000	0	-10000	0	0
EDN1	-0.12	0.14	-10000	0	-0.62	16	16
IGFBP1	-0.91	0.52	-10000	0	-1.3	275	275
VEGFA	-0.68	0.34	-10000	0	-1	218	218
HIF1A/JAB1	-0.063	0.056	-10000	0	-0.58	2	2
CP	-1	0.53	-10000	0	-1.3	348	348
CXCL12	-0.88	0.48	-10000	0	-1.3	274	274
COPS5	0.025	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4	0.045	0.009	-10000	0	-10000	0	0
BNIP3	-0.87	0.48	-10000	0	-1.3	271	271
EGLN3	-1.1	0.48	-10000	0	-1.3	370	370
CA9	-1.1	0.47	-10000	0	-1.3	383	383
TERT	-0.89	0.5	-10000	0	-1.3	276	276
ENO1	-0.87	0.48	-10000	0	-1.3	261	261
PFKL	-0.87	0.48	-10000	0	-1.2	279	279
NCOA1	0.029	0.005	-10000	0	-10000	0	0
ADM	-0.93	0.51	-10000	0	-1.3	286	286
ARNT	-0.11	0.055	-10000	0	-10000	0	0
HNF4A	-0.017	0.17	-10000	0	-0.64	38	38
ADFP	-0.88	0.48	-10000	0	-1.2	302	302
SLC2A1	-0.58	0.3	-10000	0	-0.91	153	153
LEP	-0.88	0.5	-10000	0	-1.3	275	275
HIF1A/ARNT/Cbp/p300	-0.65	0.32	-10000	0	-0.94	213	213
EPO	-0.54	0.32	-10000	0	-0.9	182	182
CREBBP	-0.1	0.076	-10000	0	-0.4	5	5
HIF1A/ARNT/Cbp/p300/HDAC7	-0.67	0.35	-10000	0	-1	208	208
PFKFB3	-0.87	0.48	-10000	0	-1.3	272	272
NT5E	-0.87	0.48	-10000	0	-1.3	271	271

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.024	0.073	-10000	0	-0.6	7	7
CDKN2C	0.078	0.023	-10000	0	-10000	0	0
CDKN2A	-0.58	0.13	-10000	0	-0.6	503	503
CCND2	0.14	0.055	0.22	92	-10000	0	92
RB1	-0.15	0.063	0.27	1	-0.24	93	94
CDK4	0.16	0.063	0.17	493	-10000	0	493
CDK6	0.15	0.066	0.25	89	-0.16	1	90
G1/S progression	0.15	0.064	0.24	95	-0.27	1	96

×

TCGA08_p53

Figure S4. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S4. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.42	0.099	0.17	3	-0.44	503	506
TP53	-0.12	0.075	-10000	0	-0.37	34	34
Senescence	-0.12	0.075	-10000	0	-0.37	34	34
Apoptosis	-0.12	0.075	-10000	0	-0.37	34	34
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.22	0.096	0.23	503	-10000	0	503
MDM4	0.029	0.006	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.029	0.027	-9999	-0.59	1	1
EGFR	0.02	0.067	-9999	-0.6	6	6
EGF/EGFR	-0.29	0.13	-9999	-0.35	425	425
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.28	0.14	-9999	-0.35	399	399
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.028	0.027	-9999	-0.59	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.57	0.2	-9999	-0.63	474	474
EGF/EGFR dimer/SHC	-0.34	0.15	-9999	-0.41	411	411
mol:GDP	-0.28	0.14	-9999	-0.34	399	399
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.008	0.11	-9999	-0.59	18	18
GRB2/SOS1	0.043	0.01	-9999	-10000	0	0
HRAS/GTP	-0.26	0.12	-9999	-0.6	6	6
SHC1	0.029	0.007	-9999	-10000	0	0
HRAS/GDP	-0.26	0.13	-9999	-0.61	6	6
FRAP1	-0.27	0.12	-9999	-0.33	399	399
EGF/EGFR dimer	-0.4	0.16	-9999	-0.48	425	425
SOS1	0.029	0.005	-9999	-10000	0	0
GRB2	0.029	0.005	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.025	0.09	-9999	-0.43	19	19

×

TCR signaling in naïve CD8+ T cells

Figure S6. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.24	0.3	0.29	5	-0.57	218	223
FYN	-0.3	0.39	0.41	13	-0.69	232	245
LAT/GRAP2/SLP76	-0.29	0.33	0.34	4	-0.64	218	222
IKBKB	0.028	0.008	-10000	0	-10000	0	0
AKT1	-0.2	0.28	0.42	22	-0.48	229	251
B2M	0.026	0.007	-10000	0	-10000	0	0
IKBKG	-0.055	0.085	0.16	11	-0.17	73	84
MAP3K8	0.027	0.038	-10000	0	-0.59	2	2
mol:Ca2+	-0.088	0.054	0.071	12	-0.13	285	297
integrin-mediated signaling pathway	0.024	0.073	-10000	0	-0.37	17	17
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.31	0.4	0.47	16	-0.72	233	249
TRPV6	-0.44	0.41	0.7	45	-0.64	406	451
CD28	-0.019	0.16	-10000	0	-0.6	39	39
SHC1	-0.33	0.39	0.42	6	-0.72	234	240
receptor internalization	-0.36	0.4	0.46	1	-0.75	248	249
PRF1	-0.33	0.42	0.41	1	-0.82	201	202
KRAS	0.029	0.006	-10000	0	-10000	0	0
GRB2	0.029	0.005	-10000	0	-10000	0	0
COT/AKT1	-0.15	0.23	0.39	20	-0.38	207	227
LAT	-0.38	0.43	0.39	5	-0.8	241	246
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.25	0.31	-10000	0	-0.6	235	235
CD3E	-0.22	0.31	-10000	0	-0.6	211	211
CD3G	-0.21	0.3	-10000	0	-0.6	203	203
RASGRP2	-0.014	0.029	0.1	3	-0.11	4	7
RASGRP1	-0.17	0.28	0.46	24	-0.46	208	232
HLA-A	-0.004	0.008	0.062	1	-10000	0	1
RASSF5	0.009	0.11	-10000	0	-0.59	17	17
RAP1A/GTP/RAPL	0.025	0.073	-10000	0	-0.37	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.14	0.31	38	-0.13	4	42
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.12	0.12	-10000	0	-0.27	162	162
PRKCA	-0.11	0.16	0.23	10	-0.3	162	172
GRAP2	-0.012	0.16	-10000	0	-0.59	35	35
mol:IP3	-0.13	0.3	0.24	149	-0.46	201	350
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.3	0.38	0.26	1	-0.7	226	227
ORAI1	0.2	0.26	0.67	6	-0.62	23	29
CSK	-0.34	0.39	0.35	5	-0.73	237	242
B7 family/CD28	-0.36	0.45	0.32	2	-0.82	224	226
CHUK	0.029	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.39	0.45	-10000	0	-0.83	242	242
PTPN6	-0.32	0.39	0.26	2	-0.72	233	235
VAV1	-0.37	0.43	0.47	5	-0.8	240	245
Monovalent TCR/CD3	-0.26	0.32	-10000	0	-0.61	226	226
CBL	0.028	0.029	-10000	0	-0.64	1	1
LCK	-0.31	0.4	0.44	10	-0.72	233	243
PAG1	-0.34	0.39	0.28	2	-0.74	235	237
RAP1A	0.029	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.37	0.44	-10000	0	-0.82	235	235
CD80	-0.11	0.26	-10000	0	-0.6	116	116
CD86	-0.071	0.23	-10000	0	-0.6	82	82
PDK1/CARD11/BCL10/MALT1	-0.14	0.16	0.16	1	-0.32	173	174
HRAS	0.029	0.027	-10000	0	-0.59	1	1
GO:0035030	-0.29	0.34	0.38	4	-0.64	228	232
CD8A	-0.25	0.31	-10000	0	-0.6	232	232
CD8B	-0.19	0.3	-10000	0	-0.6	185	185
PTPRC	-0.036	0.19	-10000	0	-0.6	53	53
PDK1/PKC theta	-0.24	0.35	0.54	22	-0.6	224	246
CSK/PAG1	-0.33	0.38	0.3	3	-0.73	226	229
SOS1	0.029	0.005	-10000	0	-10000	0	0
peptide-MHC class I	0.01	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.31	0.37	0.34	1	-0.72	217	218
STIM1	0.11	0.11	0.96	1	-0.6	3	4
RAS family/GTP	-0.04	0.14	0.32	29	-0.18	7	36
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.38	0.44	0.46	1	-0.81	248	249
mol:DAG	-0.18	0.22	0.15	1	-0.42	210	211
RAP1A/GDP	0.001	0.08	0.2	31	-10000	0	31
PLCG1	0.029	0.006	-10000	0	-10000	0	0
CD247	-0.17	0.29	-10000	0	-0.6	169	169
cytotoxic T cell degranulation	-0.31	0.41	0.4	1	-0.77	204	205
RAP1A/GTP	-0.005	0.01	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.24	0.33	0.43	18	-0.57	232	250
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.21	0.39	0.28	85	-0.63	206	291
NRAS	0.029	0.006	-10000	0	-10000	0	0
ZAP70	-0.32	0.31	-10000	0	-0.59	291	291
GRB2/SOS1	0.043	0.01	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.3	0.33	0.27	2	-0.65	221	223
MALT1	0.029	0.005	-10000	0	-10000	0	0
TRAF6	0.03	0.003	-10000	0	-10000	0	0
CD8 heterodimer	-0.3	0.39	-10000	0	-0.71	238	238
CARD11	-0.089	0.24	-10000	0	-0.59	98	98
PRKCB	-0.12	0.16	0.21	8	-0.3	180	188
PRKCE	-0.12	0.16	0.18	30	-0.3	185	215
PRKCQ	-0.3	0.39	0.46	21	-0.69	233	254
LCP2	-0.011	0.14	-10000	0	-0.59	29	29
BCL10	0.029	0.006	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.16	0.24	0.4	23	-0.4	226	249
IKK complex	-0.006	0.14	0.27	63	-0.13	4	67
RAS family/GDP	-0.012	0.013	-10000	0	-0.081	1	1
MAP3K14	-0.11	0.18	0.34	19	-0.3	184	203
PDPK1	-0.18	0.27	0.46	22	-0.45	223	245
TCR/CD3/MHC I/CD8/Fyn	-0.36	0.44	0.42	1	-0.84	227	228

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.22	0.32	-10000	0	-0.63	202	202
PDGF/PDGFRA/CRKL	-0.15	0.24	-10000	0	-0.46	196	196
positive regulation of JUN kinase activity	-0.083	0.2	-10000	0	-0.35	177	177
CRKL	0.03	0.004	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.16	0.24	-10000	0	-0.46	202	202
AP1	-0.12	0.22	0.47	1	-1	12	13
mol:IP3	-0.16	0.24	-10000	0	-0.47	193	193
PLCG1	-0.16	0.24	-10000	0	-0.47	193	193
PDGF/PDGFRA/alphaV Integrin	-0.14	0.24	-10000	0	-0.46	190	190
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0
CRK	0.029	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.16	0.24	-10000	0	-0.47	193	193
CAV3	0.012	0.05	-10000	0	-0.63	3	3
CAV1	-0.009	0.14	-10000	0	-0.59	30	30
SHC/Grb2/SOS1	-0.082	0.2	-10000	0	-0.35	177	177
PDGF/PDGFRA/Shf	-0.15	0.24	-10000	0	-0.46	198	198
FOS	-0.13	0.21	-10000	0	-1	12	12
JUN	-0.024	0.022	-10000	0	-10000	0	0
oligodendrocyte development	-0.14	0.24	-10000	0	-0.46	190	190
GRB2	0.029	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:DAG	-0.16	0.24	-10000	0	-0.47	193	193
PDGF/PDGFRA	-0.22	0.32	-10000	0	-0.63	202	202
actin cytoskeleton reorganization	-0.15	0.24	-10000	0	-0.46	198	198
SRF	0.025	0.01	-10000	0	-10000	0	0
SHC1	0.029	0.007	-10000	0	-10000	0	0
PI3K	-0.1	0.21	-10000	0	-0.39	171	171
PDGF/PDGFRA/Crk/C3G	-0.11	0.22	-10000	0	-0.39	196	196
JAK1	-0.16	0.23	-10000	0	-0.46	198	198
ELK1/SRF	-0.11	0.18	-10000	0	-0.35	179	179
SHB	0.029	0.006	-10000	0	-10000	0	0
SHF	0.028	0.029	-10000	0	-0.64	1	1
CSNK2A1	0.037	0.017	-10000	0	-10000	0	0
GO:0007205	-0.17	0.24	-10000	0	-0.48	198	198
SOS1	0.029	0.005	-10000	0	-10000	0	0
Ras protein signal transduction	-0.083	0.2	-10000	0	-0.35	177	177
PDGF/PDGFRA/SHB	-0.15	0.24	-10000	0	-0.46	198	198
PDGF/PDGFRA/Caveolin-1	-0.17	0.25	-10000	0	-0.47	201	201
ITGAV	0.029	0.007	-10000	0	-10000	0	0
ELK1	-0.15	0.21	-10000	0	-0.42	191	191
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
PDGF/PDGFRA/Crk	-0.15	0.24	-10000	0	-0.46	197	197
JAK-STAT cascade	-0.16	0.23	-10000	0	-0.46	198	198
cell proliferation	-0.15	0.24	-10000	0	-0.46	198	198

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.44	0.41	-10000	0	-1.1	111	111
PCK1	-0.9	0.67	-10000	0	-1.4	286	286
HNF4A	-0.52	0.49	-10000	0	-1.2	122	122
KCNJ11	-0.44	0.45	-10000	0	-1.1	108	108
AKT1	-0.2	0.2	-10000	0	-0.84	13	13
response to starvation	-0.015	0.027	-10000	0	-10000	0	0
DLK1	-0.53	0.51	-10000	0	-1.2	147	147
NKX2-1	-0.075	0.17	0.34	5	-0.44	13	18
ACADM	-0.43	0.42	-10000	0	-1.1	97	97
TAT	-0.48	0.31	-10000	0	-0.86	144	144
CEBPB	-0.022	0.089	-10000	0	-0.65	8	8
CEBPA	-0.022	0.093	-10000	0	-0.63	10	10
TTR	-0.84	0.47	-10000	0	-1.1	327	327
PKLR	-0.48	0.49	-10000	0	-1.2	122	122
APOA1	-0.53	0.49	-10000	0	-1.2	120	120
CPT1C	-0.44	0.42	-10000	0	-1.1	94	94
ALAS1	-0.22	0.21	-10000	0	-0.72	14	14
TFRC	-0.63	0.39	-10000	0	-0.95	251	251
FOXF1	0.019	0.076	-10000	0	-0.59	8	8
NF1	0.036	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	-0.012	0.082	-10000	0	-0.68	4	4
CPT1A	-0.44	0.41	-10000	0	-1.1	110	110
HMGCS1	-0.42	0.41	-10000	0	-1.1	107	107
NR3C1	0.007	0.058	-10000	0	-0.67	1	1
CPT1B	-0.45	0.43	-10000	0	-1.1	122	122
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.03	0.007	-10000	0	-10000	0	0
GCK	-0.43	0.42	-10000	0	-1.1	105	105
CREB1	-0.038	0.08	-10000	0	-0.31	2	2
IGFBP1	-0.25	0.32	-10000	0	-0.8	95	95
PDX1	-0.19	0.2	-10000	0	-0.84	9	9
UCP2	-0.44	0.41	-10000	0	-1	113	113
ALDOB	-0.88	0.56	-10000	0	-1.2	381	381
AFP	-0.64	0.44	-10000	0	-0.86	328	328
BDH1	-0.56	0.5	-10000	0	-1.1	184	184
HADH	-0.44	0.43	-10000	0	-1.1	109	109
F2	-0.58	0.5	-10000	0	-1.3	126	126
HNF1A	-0.012	0.082	-10000	0	-0.68	4	4
G6PC	-0.77	0.63	-10000	0	-1.4	247	247
SLC2A2	-0.31	0.43	-10000	0	-1.5	47	47
INS	0.001	0.062	-10000	0	-10000	0	0
FOXA1	-0.31	0.28	-10000	0	-0.68	152	152
FOXA3	-0.56	0.3	-10000	0	-0.73	356	356
FOXA2	-0.5	0.49	-10000	0	-1.2	125	125
ABCC8	-0.44	0.43	-10000	0	-1.1	99	99
ALB	-1.1	0.43	-10000	0	-1.2	454	454

×

Syndecan-4-mediated signaling events

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
PTK2	-0.1	0.16	-10000	0	-0.7	16	16
Syndecan-4/Syndesmos	-0.31	0.26	-10000	0	-0.6	179	179
positive regulation of JNK cascade	-0.37	0.28	-10000	0	-0.67	201	201
Syndecan-4/ADAM12	-0.39	0.33	-10000	0	-0.7	228	228
CCL5	-0.23	0.3	-10000	0	-0.59	220	220
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
DNM2	0.03	0.003	-10000	0	-10000	0	0
ITGA5	-0.012	0.15	-10000	0	-0.59	35	35
SDCBP	0.028	0.007	-10000	0	-10000	0	0
PLG	-0.29	0.32	-10000	0	-0.59	270	270
ADAM12	-0.13	0.27	-10000	0	-0.59	138	138
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.029	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.085	0.064	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.32	0.27	-10000	0	-0.62	178	178
Syndecan-4/CXCL12/CXCR4	-0.4	0.31	-10000	0	-0.73	198	198
Syndecan-4/Laminin alpha3	-0.32	0.26	-10000	0	-0.6	184	184
MDK	-0.015	0.16	-10000	0	-0.59	38	38
Syndecan-4/FZD7	-0.32	0.26	-10000	0	-0.66	128	128
Syndecan-4/Midkine	-0.34	0.28	-10000	0	-0.62	196	196
FZD7	0.027	0.03	-10000	0	-0.64	1	1
Syndecan-4/FGFR1/FGF	-0.29	0.25	-10000	0	-0.62	121	121
THBS1	0.026	0.05	-10000	0	-0.64	3	3
integrin-mediated signaling pathway	-0.31	0.25	-10000	0	-0.58	186	186
positive regulation of MAPKKK cascade	-0.37	0.28	-10000	0	-0.67	201	201
Syndecan-4/TACI	-0.34	0.29	-10000	0	-0.64	197	197
CXCR4	-0.19	0.29	-10000	0	-0.59	182	182
cell adhesion	0.016	0.078	0.23	2	-0.31	10	12
Syndecan-4/Dynamin	-0.32	0.26	-10000	0	-0.65	132	132
Syndecan-4/TSP1	-0.32	0.26	-10000	0	-0.6	182	182
Syndecan-4/GIPC	-0.32	0.26	-10000	0	-0.6	177	177
Syndecan-4/RANTES	-0.43	0.31	-10000	0	-0.69	261	261
ITGB1	0.029	0.004	-10000	0	-10000	0	0
LAMA1	0.013	0.098	-10000	0	-0.56	14	14
LAMA3	0.022	0.066	-10000	0	-0.59	6	6
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCA	0.089	0.13	1	9	-10000	0	9
Syndecan-4/alpha-Actinin	-0.32	0.26	-10000	0	-0.6	181	181
TFPI	0.019	0.074	-10000	0	-0.57	8	8
F2	-0.2	0.3	-10000	0	-0.59	196	196
alpha5/beta1 Integrin	0.011	0.12	-10000	0	-0.43	35	35
positive regulation of cell adhesion	-0.31	0.26	-10000	0	-0.66	127	127
ACTN1	0.026	0.03	-10000	0	-0.64	1	1
TNC	0.014	0.099	-10000	0	-0.64	12	12
Syndecan-4/CXCL12	-0.32	0.27	-10000	0	-0.6	185	185
FGF6	0.017	0.004	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
CXCL12	0.017	0.086	-10000	0	-0.55	11	11
TNFRSF13B	-0.034	0.18	-10000	0	-0.59	52	52
FGF2	0.023	0.064	-10000	0	-0.63	5	5
FGFR1	0.027	0.009	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.32	0.26	-10000	0	-0.57	218	218
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.001	0.16	-10000	0	-0.57	38	38
cell migration	-0.028	0.021	-10000	0	-10000	0	0
PRKCD	0.03	0.035	-10000	0	-0.57	1	1
vasculogenesis	-0.31	0.25	-10000	0	-0.58	183	183
SDC4	-0.34	0.28	-10000	0	-0.61	218	218
Syndecan-4/Tenascin C	-0.32	0.26	-10000	0	-0.6	186	186
Syndecan-4/PI-4-5-P2/PKC alpha	-0.067	0.05	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.31	0.26	-10000	0	-0.6	177	177
MMP9	-0.24	0.31	-10000	0	-0.59	234	234
Rac1/GTP	0.016	0.079	0.24	2	-0.32	9	11
cytoskeleton organization	-0.3	0.25	-10000	0	-0.57	182	182
GIPC1	0.029	0.029	-10000	0	-0.64	1	1
Syndecan-4/TFPI	-0.32	0.26	-10000	0	-0.6	181	181

×

Aurora B 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
Condensin I complex	-0.12	0.2	-10000	0	-0.4	149	149
STMN1	-0.18	0.22	-10000	0	-0.43	244	244
Aurora B/RasGAP/Survivin	-0.22	0.31	-10000	0	-0.55	231	231
Chromosomal passenger complex/Cul3 protein complex	-0.092	0.16	-10000	0	-0.31	144	144
BIRC5	-0.15	0.28	-10000	0	-0.6	149	149
DES	-0.26	0.3	-10000	0	-0.66	160	160
Aurora C/Aurora B/INCENP	-0.12	0.2	-10000	0	-0.33	239	239
Aurora B/TACC1	-0.15	0.2	-10000	0	-0.36	243	243
Aurora B/PP2A	-0.17	0.24	-10000	0	-0.42	243	243
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.036	0.06	-10000	0	-0.22	3	3
mitotic metaphase/anaphase transition	0	0.006	-10000	0	-10000	0	0
NDC80	-0.26	0.32	-10000	0	-0.57	247	247
Cul3 protein complex	0.042	0.079	-10000	0	-0.4	15	15
KIF2C	-0.082	0.15	-10000	0	-0.29	118	118
PEBP1	0.023	0.011	-10000	0	-10000	0	0
KIF20A	-0.18	0.29	-10000	0	-0.59	176	176
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.17	0.23	-10000	0	-0.43	219	219
SEPT1	-0.052	0.21	-10000	0	-0.59	68	68
SMC2	0.029	0.006	-10000	0	-10000	0	0
SMC4	0.029	0.007	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.059	0.17	-10000	0	-0.72	11	11
PSMA3	0.028	0.008	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-10000	0	-10000	0	0
H3F3B	-0.099	0.13	-10000	0	-0.24	239	239
AURKB	-0.26	0.31	-10000	0	-0.59	244	244
AURKC	0.027	0.038	-10000	0	-0.59	2	2
CDCA8	-0.006	0.12	-10000	0	-0.62	20	20
cytokinesis	-0.17	0.22	-10000	0	-0.49	135	135
Aurora B/Septin1	-0.18	0.28	-10000	0	-0.57	138	138
AURKA	0.024	0.061	-10000	0	-0.6	5	5
INCENP	0.017	0.02	-10000	0	-10000	0	0
KLHL13	0.01	0.11	-10000	0	-0.62	16	16
BUB1	-0.24	0.31	-10000	0	-0.59	225	225
hSgo1/Aurora B/Survivin	-0.23	0.31	-10000	0	-0.52	246	246
EVI5	0.028	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.14	0.22	-10000	0	-0.46	122	122
SGOL1	0	0.12	-10000	0	-0.61	18	18
CENPA	-0.15	0.2	0.19	1	-0.39	191	192
NCAPG	-0.18	0.29	-10000	0	-0.59	173	173
Aurora B/HC8 Proteasome	-0.17	0.23	-10000	0	-0.42	243	243
NCAPD2	0.029	0.006	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.17	0.23	-10000	0	-0.43	235	235
RHOA	0.021	0.014	-10000	0	-10000	0	0
NCAPH	-0.073	0.23	-10000	0	-0.59	86	86
NPM1	-0.098	0.14	-10000	0	-0.62	6	6
RASA1	0.025	0.03	-10000	0	-0.64	1	1
KLHL9	0.029	0.006	-10000	0	-10000	0	0
mitotic prometaphase	-0.006	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.17	0.23	-10000	0	-0.42	243	243
PPP1CC	0.029	0.005	-10000	0	-10000	0	0
Centraspindlin	-0.15	0.24	-10000	0	-0.47	150	150
RhoA/GDP	0.016	0.01	-10000	0	-10000	0	0
NSUN2	-0.1	0.14	-10000	0	-0.61	6	6
MYLK	-0.1	0.14	-10000	0	-0.25	242	242
KIF23	0.017	0.077	-10000	0	-0.6	8	8
VIM	-0.22	0.27	-10000	0	-0.48	256	256
RACGAP1	0.025	0.028	-10000	0	-0.6	1	1
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.12	0.17	-10000	0	-0.65	17	17
Chromosomal passenger complex	-0.17	0.24	-10000	0	-0.45	188	188
Chromosomal passenger complex/EVI5	-0.18	0.32	-10000	0	-0.64	146	146
TACC1	0.027	0.009	-10000	0	-10000	0	0
PPP2R5D	0.029	0.006	-10000	0	-10000	0	0
CUL3	0.029	0.007	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.11	0.18	-10000	0	-0.45	67	67
TBX21	-0.41	0.53	0.79	1	-1.1	154	155
B2M	0.023	0.014	-10000	0	-10000	0	0
TYK2	0.003	0.037	-10000	0	-10000	0	0
IL12RB1	-0.18	0.3	-10000	0	-0.63	159	159
GADD45B	-0.22	0.34	0.61	1	-0.75	62	63
IL12RB2	-0.084	0.22	-10000	0	-0.6	76	76
GADD45G	-0.23	0.34	0.61	1	-0.74	76	77
natural killer cell activation	-0.011	0.026	0.051	3	-0.043	85	88
RELB	0.03	0.003	-10000	0	-10000	0	0
RELA	0.03	0.003	-10000	0	-10000	0	0
IL18	0.022	0.061	-10000	0	-0.58	5	5
IL2RA	-0.09	0.24	-10000	0	-0.59	101	101
IFNG	-0.24	0.31	-10000	0	-0.59	232	232
STAT3 (dimer)	-0.29	0.38	-10000	0	-0.78	159	159
HLA-DRB5	0	0.003	-10000	0	-0.023	10	10
FASLG	-0.44	0.54	0.79	1	-1.1	177	178
NF kappa B2 p52/RelB	-0.34	0.46	-10000	0	-0.96	155	155
CD4	0.018	0.081	-10000	0	-0.59	9	9
SOCS1	0.022	0.066	-10000	0	-0.59	6	6
EntrezGene:6955	-0.003	0.009	-10000	0	-0.025	46	46
CD3D	-0.25	0.31	-10000	0	-0.6	235	235
CD3E	-0.23	0.31	-10000	0	-0.6	211	211
CD3G	-0.22	0.31	-10000	0	-0.6	203	203
IL12Rbeta2/JAK2	-0.061	0.17	-10000	0	-0.46	76	76
CCL3	-0.37	0.5	0.79	1	-1	147	148
CCL4	-0.38	0.52	0.79	1	-1.1	146	147
HLA-A	-0.004	0.008	-10000	0	-0.026	37	37
IL18/IL18R	-0.066	0.21	-10000	0	-0.39	141	141
NOS2	-0.28	0.37	-10000	0	-0.84	99	99
IL12/IL12R/TYK2/JAK2/SPHK2	-0.11	0.18	-10000	0	-0.45	62	62
IL1R1	-0.34	0.47	0.79	1	-0.98	141	142
IL4	0.017	0.037	-10000	0	-10000	0	0
JAK2	0.003	0.037	-10000	0	-10000	0	0
EntrezGene:6957	-0.003	0.009	-10000	0	-0.025	47	47
TCR/CD3/MHC I/CD8	-0.4	0.48	-10000	0	-0.9	232	232
RAB7A	-0.18	0.31	0.56	4	-0.69	25	29
lysosomal transport	-0.17	0.3	0.55	5	-0.66	25	30
FOS	-0.29	0.38	-10000	0	-0.74	173	173
STAT4 (dimer)	-0.3	0.43	0.58	5	-0.85	147	152
STAT5A (dimer)	-0.44	0.54	-10000	0	-1	202	202
GZMA	-0.41	0.54	0.52	1	-1	189	190
GZMB	-0.4	0.52	-10000	0	-1.1	165	165
HLX	-0.045	0.2	-10000	0	-0.59	62	62
LCK	-0.39	0.52	0.56	1	-1.1	157	158
TCR/CD3/MHC II/CD4	-0.22	0.27	-10000	0	-0.51	226	226
IL2/IL2R	-0.23	0.3	-10000	0	-0.45	299	299
MAPK14	-0.22	0.35	0.62	1	-0.75	79	80
CCR5	-0.4	0.45	0.61	1	-0.94	174	175
IL1B	-0.005	0.075	-10000	0	-0.61	6	6
STAT6	-0.073	0.12	-10000	0	-10000	0	0
STAT4	-0.007	0.14	-10000	0	-0.59	30	30
STAT3	0.029	0.004	-10000	0	-10000	0	0
STAT1	0.027	0.028	-10000	0	-0.59	1	1
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
NFKB2	0.029	0.006	-10000	0	-10000	0	0
IL12B	-0.061	0.19	-10000	0	-0.62	54	54
CD8A	-0.25	0.31	-10000	0	-0.6	232	232
CD8B	-0.2	0.3	-10000	0	-0.6	185	185
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.11	0.18	0.45	67	-10000	0	67
IL2RB	-0.29	0.31	-10000	0	-0.59	272	272
proteasomal ubiquitin-dependent protein catabolic process	-0.27	0.39	0.57	5	-0.77	146	151
IL2RG	-0.01	0.15	-10000	0	-0.59	34	34
IL12	-0.044	0.15	-10000	0	-0.48	54	54
STAT5A	0.029	0.004	-10000	0	-10000	0	0
CD247	-0.18	0.29	-10000	0	-0.6	169	169
IL2	0.013	0.084	-10000	0	-0.59	10	10
SPHK2	0.027	0.041	-10000	0	-0.64	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.002	0.037	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.42	0.53	-10000	0	-1.1	158	158
MAP2K3	-0.22	0.35	0.61	1	-0.73	94	95
RIPK2	0.027	0.028	-10000	0	-0.59	1	1
MAP2K6	-0.22	0.35	0.61	1	-0.75	81	82
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0	0.004	-10000	0	-0.027	10	10
IL18RAP	-0.13	0.27	-10000	0	-0.6	136	136
IL12Rbeta1/TYK2	-0.13	0.24	-10000	0	-0.48	159	159
EOMES	-0.32	0.33	-10000	0	-0.64	159	159
STAT1 (dimer)	-0.34	0.41	-10000	0	-0.82	183	183
T cell proliferation	-0.21	0.31	0.48	5	-0.61	125	130
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.018	0.074	-10000	0	-0.61	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.28	0.3	-10000	0	-0.7	113	113
ATF2	-0.2	0.34	0.57	6	-0.71	69	75

×

Glypican 1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.047	0.052	-10000	0	-0.4	6	6
fibroblast growth factor receptor signaling pathway	0.046	0.052	-10000	0	-0.4	6	6
LAMA1	0.013	0.098	-10000	0	-0.56	14	14
PRNP	0.029	0.005	-10000	0	-10000	0	0
GPC1/SLIT2	-0.068	0.21	-10000	0	-0.47	108	108
SMAD2	0.022	0.027	-10000	0	-0.37	1	1
GPC1/PrPc/Cu2+	0.036	0.022	-10000	0	-0.41	1	1
GPC1/Laminin alpha1	0.029	0.076	-10000	0	-0.46	11	11
TDGF1	-0.4	0.27	-10000	0	-0.54	394	394
CRIPTO/GPC1	-0.29	0.21	-10000	0	-0.47	272	272
APP/GPC1	0.04	0.026	-10000	0	-0.47	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.24	0.18	-10000	0	-0.4	269	269
FLT1	0.023	0.06	-10000	0	-0.59	5	5
GPC1/TGFB/TGFBR1/TGFBR2	0.041	0.034	-10000	0	-0.4	1	1
SERPINC1	-0.028	0.18	-10000	0	-0.63	44	44
FYN	-0.24	0.18	-10000	0	-0.4	271	271
FGR	-0.24	0.18	-10000	0	-0.41	272	272
positive regulation of MAPKKK cascade	-0.28	0.2	0.38	3	-0.44	280	283
SLIT2	-0.11	0.27	-10000	0	-0.62	116	116
GPC1/NRG	0.023	0.085	-10000	0	-0.47	14	14
NRG1	0.008	0.11	-10000	0	-0.56	17	17
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.14	0.22	-10000	0	-0.38	229	229
LYN	-0.24	0.18	-10000	0	-0.4	263	263
mol:Spermine	0.01	0.021	-10000	0	-0.47	1	1
cell growth	0.046	0.052	-10000	0	-0.4	6	6
BMP signaling pathway	-0.027	0.03	0.63	1	-10000	0	1
SRC	-0.24	0.18	-10000	0	-0.4	264	264
TGFBR1	0.029	0.006	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.025	0.17	-10000	0	-0.59	43	43
GPC1	0.027	0.03	-10000	0	-0.64	1	1
TGFBR1 (dimer)	0.029	0.006	-10000	0	-10000	0	0
VEGFA	-0.25	0.31	-10000	0	-0.59	234	234
BLK	-0.26	0.21	-10000	0	-0.44	276	276
HCK	-0.26	0.19	-10000	0	-0.42	277	277
FGF2	0.023	0.064	-10000	0	-0.63	5	5
FGFR1	0.027	0.009	-10000	0	-10000	0	0
VEGFR1 homodimer	0.023	0.06	-10000	0	-0.59	5	5
TGFBR2	0.022	0.014	-10000	0	-10000	0	0
cell death	0.04	0.025	-10000	0	-0.47	1	1
ATIII/GPC1	-0.004	0.14	-10000	0	-0.47	45	45
PLA2G2A/GPC1	-0.002	0.13	-10000	0	-0.43	44	44
LCK	-0.26	0.19	-10000	0	-0.42	280	280
neuron differentiation	0.023	0.085	-10000	0	-0.46	14	14
PrPc/Cu2+	0.021	0.004	-10000	0	-10000	0	0
APP	0.029	0.006	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.021	0.014	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.14	0.54	0.78	1	-1.1	86	87
PLK1	-0.051	0.26	-10000	0	-0.5	121	121
BIRC5	-0.078	0.28	-10000	0	-0.5	142	142
HSPA1B	-0.15	0.54	0.78	2	-1.1	87	89
MAP2K1	0.026	0.053	-10000	0	-10000	0	0
BRCA2	-0.15	0.54	-10000	0	-1.1	79	79
FOXM1	-0.23	0.69	-10000	0	-1.4	101	101
XRCC1	-0.15	0.53	-10000	0	-1.1	92	92
FOXM1B/p19	-0.3	0.48	-10000	0	-1.1	91	91
Cyclin D1/CDK4	-0.14	0.49	-10000	0	-1	81	81
CDC2	-0.16	0.56	-10000	0	-1.1	100	100
TGFA	-0.14	0.49	-10000	0	-0.98	82	82
SKP2	-0.14	0.54	0.72	4	-1.1	86	90
CCNE1	0.023	0.073	-10000	0	-0.6	7	7
CKS1B	-0.15	0.54	-10000	0	-1.1	101	101
RB1	-0.035	0.3	-10000	0	-0.94	13	13
FOXM1C/SP1	-0.18	0.61	-10000	0	-1.3	96	96
AURKB	-0.16	0.32	-10000	0	-1.3	8	8
CENPF	-0.17	0.57	0.69	1	-1.2	86	87
CDK4	0.026	0.025	-10000	0	-10000	0	0
MYC	-0.13	0.48	-10000	0	-0.96	88	88
CHEK2	0.024	0.067	-10000	0	-0.64	2	2
ONECUT1	-0.15	0.52	-10000	0	-1.1	91	91
CDKN2A	-0.56	0.13	-10000	0	-0.59	503	503
LAMA4	-0.2	0.55	0.78	1	-1.1	97	98
FOXM1B/HNF6	-0.2	0.61	-10000	0	-1.3	93	93
FOS	-0.16	0.55	-10000	0	-1.1	94	94
SP1	0.029	0.009	-10000	0	-10000	0	0
CDC25B	-0.15	0.54	-10000	0	-1.1	85	85
response to radiation	0.005	0.036	-10000	0	-10000	0	0
CENPB	-0.15	0.54	-10000	0	-1.1	87	87
CENPA	-0.21	0.61	-10000	0	-1.2	112	112
NEK2	-0.19	0.59	0.69	1	-1.2	101	102
HIST1H2BA	-0.16	0.54	0.78	1	-1.1	87	88
CCNA2	-0.09	0.25	-10000	0	-0.6	101	101
EP300	0.028	0.029	-10000	0	-0.64	1	1
CCNB1/CDK1	-0.19	0.62	-10000	0	-1.3	93	93
CCNB2	-0.19	0.6	0.78	1	-1.2	108	109
CCNB1	-0.16	0.57	-10000	0	-1.2	91	91
ETV5	-0.15	0.54	-10000	0	-1.1	88	88
ESR1	-0.15	0.54	0.78	1	-1.1	86	87
CCND1	-0.14	0.5	-10000	0	-1	84	84
GSK3A	0.027	0.046	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.024	0.2	-10000	0	-0.42	97	97
CDK2	0.031	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.006	0.043	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.17	0.57	-10000	0	-1.2	94	94
GAS1	-0.19	0.57	-10000	0	-1.1	108	108
MMP2	-0.15	0.54	0.78	1	-1.1	87	88
RB1/FOXM1C	-0.16	0.54	-10000	0	-1.1	88	88
CREBBP	0.029	0.006	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.047	0.2	-10000	0	-0.43	103	103
alphaM/beta2 Integrin/GPIbA	-0.045	0.2	-10000	0	-0.43	100	100
alphaM/beta2 Integrin/proMMP-9	-0.21	0.29	-10000	0	-0.48	256	256
PLAUR	0	0.13	-10000	0	-0.59	25	25
HMGB1	0.025	0.022	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.045	0.2	-10000	0	-0.43	99	99
AGER	-0.088	0.24	-10000	0	-0.59	95	95
RAP1A	0.029	0.006	-10000	0	-10000	0	0
SELPLG	-0.009	0.15	-10000	0	-0.59	32	32
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.1	0.25	-10000	0	-0.61	59	59
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.25	0.31	-10000	0	-0.59	234	234
CYR61	0.023	0.057	-10000	0	-0.48	6	6
TLN1	0.029	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.19	0.16	-10000	0	-0.44	106	106
RHOA	0.021	0.014	-10000	0	-10000	0	0
P-selectin oligomer	0.001	0.13	-10000	0	-0.62	22	22
MYH2	-0.29	0.2	-10000	0	-0.51	180	180
MST1R	0.013	0.071	-10000	0	-0.58	7	7
leukocyte activation during inflammatory response	-0.14	0.24	-10000	0	-0.55	83	83
APOB	-0.17	0.29	-10000	0	-0.59	166	166
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.022	0.067	-10000	0	-0.6	6	6
JAM3	0.03	0.003	-10000	0	-10000	0	0
GP1BA	0.028	0.029	-10000	0	-0.64	1	1
alphaM/beta2 Integrin/CTGF	-0.051	0.2	-10000	0	-0.43	104	104
alphaM/beta2 Integrin	-0.23	0.18	-10000	0	-0.41	216	216
JAM3 homodimer	0.03	0.003	-10000	0	-10000	0	0
ICAM2	0.029	0.005	-10000	0	-10000	0	0
ICAM1	0.017	0.089	-10000	0	-0.59	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.23	0.18	-10000	0	-0.4	216	216
cell adhesion	-0.045	0.2	-10000	0	-0.42	100	100
NFKB1	-0.12	0.25	0.4	5	-0.63	63	68
THY1	0.028	0.029	-10000	0	-0.64	1	1
RhoA/GDP	0.016	0.01	-10000	0	-10000	0	0
Lipoprotein(a)	-0.099	0.2	-10000	0	-0.38	166	166
alphaM/beta2 Integrin/LRP/tPA	-0.031	0.19	-10000	0	-0.52	37	37
IL6	-0.15	0.3	0.39	3	-0.72	78	81
ITGB2	-0.092	0.24	-10000	0	-0.59	98	98
elevation of cytosolic calcium ion concentration	-0.046	0.21	-10000	0	-0.56	42	42
alphaM/beta2 Integrin/JAM2/JAM3	-0.022	0.19	-10000	0	-0.53	30	30
JAM2	0.029	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.042	0.19	-10000	0	-0.56	34	34
alphaM/beta2 Integrin/uPA/Plg	-0.23	0.27	-10000	0	-0.46	252	252
RhoA/GTP	-0.29	0.21	-10000	0	-0.52	190	190
positive regulation of phagocytosis	-0.19	0.2	-10000	0	-0.55	81	81
Ron/MSP	0.018	0.081	-10000	0	-0.45	14	14
alphaM/beta2 Integrin/uPAR/uPA	-0.045	0.21	-10000	0	-0.56	42	42
alphaM/beta2 Integrin/uPAR	-0.06	0.22	-10000	0	-0.45	113	113
PLAU	0.02	0.074	-10000	0	-0.56	8	8
PLAT	0.016	0.088	-10000	0	-0.6	10	10
actin filament polymerization	-0.27	0.19	-10000	0	-0.48	178	178
MST1	0.012	0.079	-10000	0	-0.61	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.14	0.25	-10000	0	-0.56	83	83
TNF	-0.11	0.24	0.39	4	-0.6	64	68
RAP1B	0.029	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.05	0.2	-10000	0	-0.43	105	105
fibrinolysis	-0.23	0.27	-10000	0	-0.46	252	252
HCK	-0.003	0.14	-10000	0	-0.59	27	27
dendritic cell antigen processing and presentation	-0.23	0.18	-10000	0	-0.4	216	216
VTN	-0.069	0.24	-10000	0	-0.62	79	79
alphaM/beta2 Integrin/CYR61	-0.047	0.2	-10000	0	-0.43	102	102
LPA	0.018	0.05	-10000	0	-0.63	3	3
LRP1	0.029	0.005	-10000	0	-10000	0	0
cell migration	-0.2	0.28	-10000	0	-0.6	111	111
FN1	-0.017	0.16	-10000	0	-0.6	38	38
alphaM/beta2 Integrin/Thy1	-0.044	0.2	-10000	0	-0.43	100	100
MPO	0.009	0.11	-10000	0	-0.59	17	17
KNG1	-0.45	0.29	-10000	0	-0.63	380	380
RAP1/GDP	0.038	0.01	-10000	0	-10000	0	0
ROCK1	-0.27	0.2	-10000	0	-0.5	173	173
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.3	0.32	-10000	0	-0.61	270	270
CTGF	0.019	0.076	-10000	0	-0.64	7	7
alphaM/beta2 Integrin/Hck	-0.06	0.24	-10000	0	-0.5	101	101
ITGAM	0.001	0.12	-10000	0	-0.59	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.056	0.24	-10000	0	-0.58	62	62
HP	-0.12	0.27	-10000	0	-0.59	128	128
leukocyte adhesion	-0.075	0.2	-10000	0	-0.54	41	41
SELP	0.001	0.13	-10000	0	-0.62	22	22

×

BMP receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.46	0.28	-10000	0	-0.56	421	421
SMAD6-7/SMURF1	0.053	0.021	-10000	0	-10000	0	0
NOG	-0.072	0.23	-10000	0	-0.6	84	84
SMAD9	-0.066	0.17	-10000	0	-0.64	38	38
SMAD4	0.029	0.005	-10000	0	-10000	0	0
SMAD5	-0.14	0.16	-10000	0	-0.49	30	30
BMP7/USAG1	-0.52	0.32	-10000	0	-0.64	434	434
SMAD5/SKI	-0.15	0.16	0.33	2	-0.48	26	28
SMAD1	-0.023	0.054	-10000	0	-10000	0	0
BMP2	0.025	0.05	-10000	0	-0.64	3	3
SMAD1/SMAD1/SMAD4	0.012	0.054	-10000	0	-10000	0	0
BMPR1A	0.029	0.006	-10000	0	-10000	0	0
BMPR1B	-0.43	0.31	-10000	0	-0.63	362	362
BMPR1A-1B/BAMBI	-0.26	0.22	-10000	0	-0.41	358	358
AHSG	0.008	0.093	-10000	0	-0.6	12	12
CER1	0.02	0.006	-10000	0	-10000	0	0
BMP2-4/CER1	0.044	0.047	-10000	0	-0.41	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.1	0.12	-10000	0	-0.46	9	9
BMP2-4 (homodimer)	0.035	0.05	-10000	0	-0.4	6	6
RGMB	0.023	0.039	-10000	0	-0.59	2	2
BMP6/BMPR2/BMPR1A-1B	-0.23	0.2	-10000	0	-0.37	346	346
RGMA	0.023	0.065	-10000	0	-0.64	5	5
SMURF1	0.027	0.009	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.12	0.14	-10000	0	-0.37	47	47
BMP2-4/USAG1	-0.21	0.22	-10000	0	-0.41	298	298
SMAD6/SMURF1/SMAD5	-0.14	0.16	0.31	1	-0.5	22	23
SOSTDC1	-0.35	0.32	-10000	0	-0.64	299	299
BMP7/BMPR2/BMPR1A-1B	-0.46	0.27	-10000	0	-0.56	430	430
SKI	0.029	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.019	0.078	-10000	0	-0.6	8	8
HFE2	0.004	0.12	-10000	0	-0.6	19	19
ZFYVE16	0.027	0.009	-10000	0	-10000	0	0
MAP3K7	0.028	0.007	-10000	0	-10000	0	0
BMP2-4/CHRD	0.043	0.072	-10000	0	-0.43	10	10
SMAD5/SMAD5/SMAD4	-0.15	0.16	0.31	1	-0.48	28	29
MAPK1	0.03	0.004	-10000	0	-10000	0	0
TAK1/TAB family	-0.1	0.12	-10000	0	-0.39	17	17
BMP7 (homodimer)	-0.4	0.31	-10000	0	-0.63	340	340
NUP214	0.029	0.005	-10000	0	-10000	0	0
BMP6/FETUA	0.02	0.087	-10000	0	-0.45	16	16
SMAD1/SKI	-0.018	0.066	0.34	1	-0.42	1	2
SMAD6	0.03	0.003	-10000	0	-10000	0	0
CTDSP2	0.029	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.036	0.076	-10000	0	-0.38	15	15
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.14	0.29	-10000	0	-0.63	132	132
BMPR2 (homodimer)	0.029	0.007	-10000	0	-10000	0	0
GADD34/PP1CA	0.054	0.02	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.31	0.24	-10000	0	-0.47	356	356
CHRDL1	-0.31	0.33	-10000	0	-0.63	271	271
ENDOFIN/SMAD1	-0.015	0.064	0.34	1	-0.44	1	2
SMAD6-7/SMURF1/SMAD1	0.016	0.066	-10000	0	-10000	0	0
SMAD6/SMURF1	0.027	0.009	-10000	0	-10000	0	0
BAMBI	0.021	0.072	-10000	0	-0.59	7	7
SMURF2	0.028	0.029	-10000	0	-0.64	1	1
BMP2-4/CHRDL1	-0.18	0.23	-10000	0	-0.41	264	264
BMP2-4/GREM1	-0.062	0.2	-10000	0	-0.4	130	130
SMAD7	0.029	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.063	0.17	-10000	0	-0.58	44	44
SMAD1/SMAD6	-0.017	0.061	-10000	0	-0.44	1	1
TAK1/SMAD6	0.037	0.016	-10000	0	-10000	0	0
BMP7	-0.4	0.31	-10000	0	-0.64	340	340
BMP6	0.019	0.078	-10000	0	-0.6	8	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.099	0.11	-10000	0	-0.35	27	27
PPM1A	0.028	0.008	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.02	0.067	0.34	1	-0.44	1	2
SMAD7/SMURF1	0.039	0.015	-10000	0	-10000	0	0
CTDSPL	0.021	0.014	-10000	0	-10000	0	0
PPP1CA	0.03	0.003	-10000	0	-10000	0	0
XIAP	0.03	0.003	-10000	0	-10000	0	0
CTDSP1	0.028	0.007	-10000	0	-10000	0	0
PPP1R15A	0.03	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.16	0.18	-10000	0	-0.47	77	77
CHRD	0.017	0.084	-10000	0	-0.62	9	9
BMPR2	0.029	0.007	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.14	0.13	-10000	0	-0.38	44	44
BMP4	0.024	0.051	-10000	0	-0.64	3	3
FST	-0.04	0.2	-10000	0	-0.63	54	54
BMP2-4/NOG	-0.017	0.16	-10000	0	-0.38	83	83
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.42	0.26	-10000	0	-0.66	248	248

×

Aurora C signaling

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
INCENP	0.03	0.003	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.13	0.2	-9999	-0.34	239	239
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.03	0.059	-9999	-0.62	1	1
AURKB	-0.26	0.31	-9999	-0.59	244	244
AURKC	0.027	0.038	-9999	-0.59	2	2

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.012	0.11	-10000	0	-0.62	14	14
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.025	0.048	-10000	0	-0.6	3	3
TCEB1	0.028	0.007	-10000	0	-10000	0	0
HIF1A/p53	-0.069	0.079	0.26	1	-0.47	14	15
HIF1A	-0.076	0.08	-10000	0	-0.49	14	14
COPS5	0.028	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.056	0.052	-10000	0	-10000	0	0
FIH (dimer)	0.029	0.006	-10000	0	-10000	0	0
CDKN2A	-0.57	0.13	-10000	0	-0.6	503	503
ARNT/IPAS	0.029	0.082	-10000	0	-0.46	14	14
HIF1AN	0.029	0.006	-10000	0	-10000	0	0
GNB2L1	0.023	0.013	-10000	0	-10000	0	0
HIF1A/ARNT	-0.067	0.081	0.26	1	-0.47	14	15
CUL2	0.029	0.004	-10000	0	-10000	0	0
OS9	0.029	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.041	0.042	-10000	0	-0.38	3	3
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.065	0.079	-10000	0	-0.47	14	14
PHD1-3/OS9	-0.28	0.13	-10000	0	-0.34	435	435
HIF1A/RACK1/Elongin B/Elongin C	-0.045	0.081	-10000	0	-0.45	13	13
VHL	0.021	0.02	-10000	0	-0.32	1	1
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
HIF1A/JAB1	-0.066	0.08	-10000	0	-0.47	14	14
EGLN3	-0.52	0.2	-10000	0	-0.6	462	462
EGLN2	0.03	0.003	-10000	0	-10000	0	0
EGLN1	0.029	0.006	-10000	0	-10000	0	0
TP53	0.029	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.13	0.26	-10000	0	-0.53	142	142
ARNT	0.029	0.007	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.03	0.004	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.36	0.1	-10000	0	-0.37	496	496

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.015	0.16	-9999	-0.59	38	38
GPC2	-0.038	0.19	-9999	-0.59	55	55
GPC2/Midkine	-0.041	0.19	-9999	-0.48	80	80
neuron projection morphogenesis	-0.041	0.19	-9999	-0.48	80	80

×

IL4-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.42	-10000	0	-1.1	84	84
STAT6 (cleaved dimer)	-0.49	0.44	-10000	0	-1.1	132	132
IGHG1	-0.16	0.16	-10000	0	-0.48	11	11
IGHG3	-0.43	0.4	-10000	0	-1	116	116
AKT1	-0.24	0.26	-10000	0	-0.71	59	59
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.18	0.22	-10000	0	-0.66	42	42
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.26	-10000	0	-0.75	46	46
THY1	-0.45	0.42	-10000	0	-1.1	81	81
MYB	-0.14	0.28	-10000	0	-0.6	139	139
HMGA1	0.028	0.028	-10000	0	-0.59	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.32	0.31	-10000	0	-0.78	110	110
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.24	0.26	-10000	0	-0.75	45	45
SP1	0.026	0.032	-10000	0	-10000	0	0
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
SOCS5	0.04	0.02	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.44	-10000	0	-1.1	123	123
SOCS1	-0.32	0.3	-10000	0	-0.76	77	77
SOCS3	-0.27	0.27	-10000	0	-0.77	49	49
FCER2	-0.38	0.37	-10000	0	-0.99	76	76
PARP14	0.028	0.009	-10000	0	-10000	0	0
CCL17	-0.46	0.43	-10000	0	-1.1	87	87
GRB2	0.029	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.23	-10000	0	-0.69	38	38
T cell proliferation	-0.45	0.44	-10000	0	-1.1	103	103
IL4R/JAK1	-0.44	0.42	-10000	0	-1.1	91	91
EGR2	-0.46	0.43	-10000	0	-1.2	87	87
JAK2	-0.02	0.038	-10000	0	-10000	0	0
JAK3	-0.094	0.25	-10000	0	-0.59	105	105
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
JAK1	0.01	0.019	-10000	0	-10000	0	0
COL1A2	-0.17	0.21	-10000	0	-0.68	35	35
CCL26	-0.44	0.43	-10000	0	-1.1	86	86
IL4R	-0.47	0.44	-10000	0	-1.2	87	87
PTPN6	0.04	0.015	-10000	0	-10000	0	0
IL13RA2	-0.51	0.5	-10000	0	-1.3	114	114
IL13RA1	-0.02	0.04	-10000	0	-10000	0	0
IRF4	-0.2	0.28	-10000	0	-0.72	82	82
ARG1	-0.15	0.19	-10000	0	-0.74	14	14
CBL	-0.3	0.3	-10000	0	-0.75	103	103
GTF3A	-0.002	0.049	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
IL13RA1/JAK2	-0.025	0.054	-10000	0	-10000	0	0
IRF4/BCL6	-0.18	0.27	-10000	0	-0.68	72	72
CD40LG	-0.047	0.2	-10000	0	-0.64	55	55
MAPK14	-0.3	0.3	-10000	0	-0.78	84	84
mitosis	-0.23	0.25	-10000	0	-0.67	59	59
STAT6	-0.5	0.48	-10000	0	-1.2	109	109
SPI1	-0.054	0.22	-10000	0	-0.59	73	73
RPS6KB1	-0.22	0.25	-10000	0	-0.67	46	46
STAT6 (dimer)	-0.5	0.47	-10000	0	-1.2	109	109
STAT6 (dimer)/PARP14	-0.46	0.44	-10000	0	-1.1	109	109
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.25	0.26	-10000	0	-0.71	68	68
FRAP1	-0.24	0.27	-10000	0	-0.71	59	59
LTA	-0.52	0.45	-10000	0	-1.2	115	115
FES	0.027	0.041	-10000	0	-0.64	2	2
T-helper 1 cell differentiation	0.49	0.47	1.2	109	-10000	0	109
CCL11	-0.65	0.57	-10000	0	-1.3	208	208
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.23	0.25	-10000	0	-0.7	56	56
IL2RG	-0.008	0.16	-10000	0	-0.59	34	34
IL10	-0.46	0.43	-10000	0	-1.1	108	108
IRS1	0.023	0.058	-10000	0	-0.64	4	4
IRS2	0.02	0.078	-10000	0	-0.6	8	8
IL4	-0.11	0.13	-10000	0	-1.1	3	3
IL5	-0.42	0.43	-10000	0	-1.1	81	81
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.34	-10000	0	-0.87	87	87
COL1A1	-0.3	0.31	-10000	0	-0.67	168	168
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.44	0.42	-10000	0	-1.2	77	77
IL2R gamma/JAK3	-0.081	0.25	-10000	0	-0.55	109	109
TFF3	-0.46	0.44	-10000	0	-1.2	87	87
ALOX15	-0.45	0.42	-10000	0	-1.1	85	85
MYBL1	-0.007	0.14	-10000	0	-0.59	30	30
T-helper 2 cell differentiation	-0.39	0.37	-10000	0	-0.94	100	100
SHC1	0.029	0.007	-10000	0	-10000	0	0
CEBPB	0.022	0.079	-10000	0	-0.6	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.23	0.25	-10000	0	-0.7	52	52
mol:PI-3-4-5-P3	-0.24	0.27	-10000	0	-0.71	59	59
PI3K	-0.25	0.28	-10000	0	-0.76	59	59
DOK2	-0.01	0.15	-10000	0	-0.59	31	31
ETS1	0.04	0.02	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.19	0.22	-10000	0	-0.66	42	42
ITGB3	-0.45	0.43	-10000	0	-1.1	94	94
PIGR	-0.79	0.66	-10000	0	-1.4	256	256
IGHE	0.032	0.073	0.3	5	-0.39	1	6
MAPKKK cascade	-0.19	0.22	-10000	0	-0.65	42	42
BCL6	0.028	0.007	-10000	0	-10000	0	0
OPRM1	-0.45	0.42	-10000	0	-1.1	83	83
RETNLB	-0.45	0.42	-10000	0	-1.1	84	84
SELP	-0.47	0.47	-10000	0	-1.2	87	87
AICDA	-0.52	0.44	-10000	0	-1.1	135	135

×

Caspase cascade in apoptosis

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
TOP1	-0.078	0.18	-10000	0	-0.37	112	112
ACTA1	-0.12	0.22	-10000	0	-0.49	112	112
NUMA1	-0.078	0.18	0.25	1	-0.38	113	114
SPTAN1	-0.12	0.22	0.26	1	-0.49	108	109
LIMK1	-0.11	0.22	0.34	2	-0.48	109	111
BIRC3	-0.064	0.22	-10000	0	-0.59	79	79
BIRC2	0.029	0.004	-10000	0	-10000	0	0
BAX	0.03	0.003	-10000	0	-10000	0	0
CASP10	-0.19	0.29	-10000	0	-0.55	188	188
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.03	0.003	-10000	0	-10000	0	0
PTK2	-0.081	0.18	0.25	1	-0.38	113	114
DIABLO	0.029	0.005	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.12	0.21	0.26	1	-0.49	108	109
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.029	0.005	-10000	0	-10000	0	0
GSN	-0.12	0.22	0.27	1	-0.49	108	109
MADD	0.03	0.003	-10000	0	-10000	0	0
TFAP2A	-0.29	0.3	-10000	0	-0.54	278	278
BID	-0.074	0.12	-10000	0	-0.28	109	109
MAP3K1	-0.03	0.078	-10000	0	-10000	0	0
TRADD	0.029	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.042	0.012	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.12	0.22	0.31	3	-0.49	108	111
CASP9	0.029	0.006	-10000	0	-10000	0	0
DNA repair	0.017	0.086	0.3	15	-0.19	3	18
neuron apoptosis	0.005	0.11	-10000	0	-0.61	14	14
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.1	0.21	-10000	0	-0.47	110	110
APAF1	0.029	0.006	-10000	0	-10000	0	0
CASP6	-0.029	0.15	0.36	2	-0.9	7	9
TRAF2	0.029	0.005	-10000	0	-10000	0	0
ICAD/CAD	-0.12	0.21	0.43	1	-0.48	108	109
CASP7	0.032	0.11	0.27	46	-0.3	11	57
KRT18	0.011	0.041	-10000	0	-0.32	1	1
apoptosis	-0.12	0.21	0.41	2	-0.48	95	97
DFFA	-0.12	0.22	-10000	0	-0.49	108	108
DFFB	-0.12	0.22	-10000	0	-0.49	108	108
PARP1	-0.017	0.087	0.19	3	-0.3	15	18
actin filament polymerization	0.093	0.21	0.45	101	-0.41	2	103
TNF	0.019	0.079	-10000	0	-0.61	8	8
CYCS	-0.047	0.11	0.19	5	-0.22	105	110
SATB1	-0.026	0.14	0.44	2	-0.83	7	9
SLK	-0.12	0.22	0.34	1	-0.5	109	110
p15 BID/BAX	-0.051	0.12	-10000	0	-0.28	2	2
CASP2	0.029	0.082	-10000	0	-0.47	2	2
JNK cascade	0.029	0.078	-10000	0	-10000	0	0
CASP3	-0.13	0.23	-10000	0	-0.52	110	110
LMNB2	0.025	0.11	0.36	11	-0.54	6	17
RIPK1	0.029	0.006	-10000	0	-10000	0	0
CASP4	0.03	0.003	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.013	0.14	-10000	0	-0.33	75	75
negative regulation of DNA binding	-0.29	0.29	-10000	0	-0.53	279	279
stress fiber formation	-0.12	0.22	0.34	1	-0.49	109	110
GZMB	-0.21	0.33	-10000	0	-0.63	190	190
CASP1	0.021	0.003	-10000	0	-10000	0	0
LMNB1	0.018	0.1	0.39	8	-0.44	5	13
APP	0.005	0.11	-10000	0	-0.62	14	14
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0.002	-10000	0	-10000	0	0
VIM	-0.11	0.21	0.28	1	-0.47	94	95
LMNA	0.022	0.11	0.36	11	-0.38	10	21
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.015	0.065	-10000	0	-0.5	2	2
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.12	0.22	0.3	1	-0.49	108	109
APAF-1/Caspase 9	-0.014	0.13	-10000	0	-0.58	22	22
nuclear fragmentation during apoptosis	-0.077	0.18	0.24	1	-0.37	113	114
CFL2	-0.098	0.22	0.41	2	-0.46	101	103
GAS2	-0.13	0.22	0.41	1	-0.49	117	118
positive regulation of apoptosis	0.027	0.11	0.36	11	-0.49	6	17
PRF1	-0.13	0.27	-10000	0	-0.59	132	132

×

Syndecan-1-mediated signaling events

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
TGFB1	0.025	0.054	-10000	0	-0.59	4	4
CCL5	-0.23	0.3	-10000	0	-0.59	220	220
SDCBP	0.028	0.007	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.14	0.17	0.27	2	-0.4	92	94
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.13	0.16	-10000	0	-0.45	51	51
Syndecan-1/Syntenin	-0.12	0.16	0.33	2	-0.46	45	47
MAPK3	-0.11	0.15	-10000	0	-0.5	23	23
HGF/MET	0.019	0.1	-10000	0	-0.47	20	20
TGFB1/TGF beta receptor Type II	0.025	0.054	-10000	0	-0.59	4	4
BSG	0.028	0.027	-10000	0	-0.59	1	1
keratinocyte migration	-0.12	0.16	-10000	0	-0.44	51	51
Syndecan-1/RANTES	-0.25	0.22	0.4	2	-0.5	185	187
Syndecan-1/CD147	-0.11	0.17	-10000	0	-0.53	23	23
Syndecan-1/Syntenin/PIP2	-0.12	0.16	0.26	1	-0.44	45	46
LAMA5	0.027	0.04	-10000	0	-0.61	2	2
positive regulation of cell-cell adhesion	-0.12	0.15	-10000	0	-0.44	45	45
MMP7	-0.09	0.26	-10000	0	-0.63	95	95
HGF	0.003	0.12	-10000	0	-0.6	20	20
Syndecan-1/CASK	-0.13	0.15	-10000	0	-0.38	92	92
Syndecan-1/HGF/MET	-0.12	0.18	-10000	0	-0.53	36	36
regulation of cell adhesion	-0.1	0.15	0.51	1	-0.49	23	24
HPSE	0.027	0.041	-10000	0	-0.64	2	2
positive regulation of cell migration	-0.14	0.17	0.27	2	-0.4	92	94
SDC1	-0.14	0.17	0.25	1	-0.4	92	93
Syndecan-1/Collagen	-0.14	0.17	0.27	2	-0.4	92	94
PPIB	0.03	0.003	-10000	0	-10000	0	0
MET	0.024	0.039	-10000	0	-0.59	2	2
PRKACA	0.03	0.002	-10000	0	-10000	0	0
MMP9	-0.25	0.31	-10000	0	-0.59	234	234
MAPK1	-0.11	0.15	0.28	1	-0.5	23	24
homophilic cell adhesion	-0.13	0.17	0.27	2	-0.4	91	93
MMP1	-0.095	0.25	-10000	0	-0.6	103	103

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.22	0.36	-10000	0	-0.76	121	121
MAP4K1	-0.22	0.3	-10000	0	-0.59	214	214
MAP3K8	0.027	0.038	-10000	0	-0.59	2	2
PRKCB	0.022	0.062	-10000	0	-0.61	5	5
DBNL	0.027	0.009	-10000	0	-10000	0	0
CRKL	0.03	0.004	-10000	0	-10000	0	0
MAP3K1	-0.078	0.16	-10000	0	-0.52	37	37
JUN	0.013	0.12	0.33	2	-0.57	14	16
MAP3K7	-0.081	0.16	-10000	0	-0.51	39	39
GRAP2	-0.012	0.16	-10000	0	-0.59	35	35
CRK	0.029	0.005	-10000	0	-10000	0	0
MAP2K4	-0.044	0.19	0.34	15	-0.49	37	52
LAT	-0.14	0.28	-10000	0	-0.59	144	144
LCP2	-0.012	0.14	-10000	0	-0.59	29	29
MAPK8	0.009	0.12	0.3	1	-0.58	16	17
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.086	0.17	-10000	0	-0.54	39	39
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.2	0.34	-10000	0	-0.73	119	119

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.027	0.009	-10000	0	-10000	0	0
LAT2	-0.076	0.15	-10000	0	-0.45	47	47
AP1	-0.044	0.16	-10000	0	-0.51	12	12
mol:PIP3	-0.099	0.3	0.44	38	-0.6	85	123
IKBKB	-0.017	0.19	0.34	62	-0.3	47	109
AKT1	-0.07	0.2	0.44	12	-0.52	20	32
IKBKG	-0.018	0.19	0.33	61	-0.3	49	110
MS4A2	-0.1	0.26	-10000	0	-0.59	114	114
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
MAP3K1	-0.048	0.2	0.38	26	-0.41	40	66
mol:Ca2+	-0.063	0.24	0.38	45	-0.43	84	129
LYN	0.025	0.012	-10000	0	-10000	0	0
CBLB	-0.051	0.11	-10000	0	-0.35	16	16
SHC1	0.029	0.007	-10000	0	-10000	0	0
RasGAP/p62DOK	0.04	0.036	-10000	0	-0.35	2	2
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
PLD2	-0.1	0.2	0.34	17	-0.59	21	38
PTPN13	-0.025	0.14	0.39	3	-0.64	10	13
PTPN11	0.026	0.014	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.006	0.17	0.43	31	-0.37	1	32
SYK	0.024	0.035	-10000	0	-0.49	2	2
GRB2	0.029	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.17	0.24	-10000	0	-0.59	108	108
LAT	-0.13	0.19	-10000	0	-0.48	87	87
PAK2	-0.071	0.2	0.38	16	-0.44	68	84
NFATC2	-0.036	0.081	-10000	0	-0.53	5	5
HRAS	-0.088	0.2	0.34	7	-0.47	74	81
GAB2	0.03	0.003	-10000	0	-10000	0	0
PLA2G1B	-0.2	0.38	-10000	0	-0.8	150	150
Fc epsilon R1	-0.13	0.24	-10000	0	-0.41	206	206
Antigen/IgE/Fc epsilon R1	-0.12	0.22	-10000	0	-0.38	206	206
mol:GDP	-0.11	0.21	0.26	1	-0.51	79	80
JUN	0.029	0.006	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.025	0.03	-10000	0	-0.64	1	1
FOS	0.013	0.099	-10000	0	-0.63	12	12
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.054	0.12	-10000	0	-0.35	23	23
CHUK	-0.019	0.19	0.33	60	-0.3	47	107
KLRG1	-0.055	0.11	-10000	0	-0.35	20	20
VAV1	-0.12	0.19	-10000	0	-0.47	92	92
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.05	0.11	-10000	0	-0.36	17	17
negative regulation of mast cell degranulation	-0.043	0.12	-10000	0	-0.46	8	8
BTK	-0.067	0.15	-10000	0	-0.44	16	16
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.07	0.16	-10000	0	-0.36	82	82
GAB2/PI3K/SHP2	-0.11	0.17	-10000	0	-0.57	21	21
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.052	0.12	-10000	0	-0.37	26	26
RAF1	-0.23	0.42	-10000	0	-0.89	150	150
Fc epsilon R1/FcgammaRIIB/SHIP	-0.15	0.28	-10000	0	-0.66	83	83
FCER1G	-0.082	0.24	-10000	0	-0.6	94	94
FCER1A	0.001	0.12	-10000	0	-0.63	19	19
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.21	-10000	0	-0.36	201	201
MAPK3	-0.2	0.38	-10000	0	-0.81	150	150
MAPK1	-0.2	0.39	-10000	0	-0.81	150	150
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MAPK8	0.007	0.14	-10000	0	-0.68	15	15
DUSP1	0.021	0.03	-10000	0	-0.59	1	1
NF-kappa-B/RelA	-0.03	0.083	-10000	0	-0.28	1	1
actin cytoskeleton reorganization	-0.022	0.14	0.4	3	-0.67	9	12
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.1	0.21	-10000	0	-0.51	70	70
FER	-0.049	0.11	-10000	0	-0.36	18	18
RELA	0.03	0.003	-10000	0	-10000	0	0
ITK	-0.056	0.11	-10000	0	-0.26	84	84
SOS1	0.029	0.005	-10000	0	-10000	0	0
PLCG1	-0.087	0.24	0.39	13	-0.52	82	95
cytokine secretion	-0.029	0.053	-10000	0	-10000	0	0
SPHK1	-0.071	0.14	-10000	0	-0.45	35	35
PTK2	-0.024	0.15	0.4	3	-0.71	9	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.22	-10000	0	-0.56	80	80
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.059	0.28	0.4	56	-0.54	72	128
MAP2K2	-0.22	0.39	-10000	0	-0.83	150	150
MAP2K1	-0.21	0.39	-10000	0	-0.83	150	150
MAP2K7	0.03	0.003	-10000	0	-10000	0	0
KLRG1/SHP2	-0.05	0.12	0.29	2	-0.37	10	12
MAP2K4	0.018	0.13	-10000	0	-0.81	12	12
Fc epsilon R1/FcgammaRIIB	-0.16	0.29	-10000	0	-0.47	224	224
mol:Choline	-0.099	0.2	0.34	17	-0.58	21	38
SHC/Grb2/SOS1	-0.019	0.13	-10000	0	-0.38	3	3
FYN	0.028	0.008	-10000	0	-10000	0	0
DOK1	0.029	0.005	-10000	0	-10000	0	0
PXN	-0.014	0.15	0.42	10	-0.67	8	18
HCLS1	-0.058	0.13	-10000	0	-0.45	25	25
PRKCB	-0.043	0.23	0.37	59	-0.41	74	133
FCGR2B	-0.078	0.23	-10000	0	-0.59	90	90
IGHE	-0.003	0.011	-10000	0	-10000	0	0
KLRG1/SHIP	-0.044	0.12	-10000	0	-0.47	8	8
LCP2	-0.012	0.14	-10000	0	-0.59	29	29
PLA2G4A	-0.052	0.12	-10000	0	-0.42	9	9
RASA1	0.025	0.03	-10000	0	-0.64	1	1
mol:Phosphatidic acid	-0.099	0.2	0.34	17	-0.58	21	38
IKK complex	0.002	0.16	0.33	61	-0.25	3	64
WIPF1	0.029	0.006	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.018	0.15	-10000	0	-0.79	14	14
oxygen homeostasis	-0.003	0.014	-10000	0	-10000	0	0
TCEB2	0.025	0.048	-10000	0	-0.6	3	3
TCEB1	0.028	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.15	0.13	-10000	0	-0.45	8	8
EPO	-0.29	0.3	-10000	0	-0.76	79	79
FIH (dimer)	0.022	0.023	-10000	0	-10000	0	0
APEX1	0.024	0.02	-10000	0	-10000	0	0
SERPINE1	-0.25	0.3	-10000	0	-0.81	65	65
FLT1	0.001	0.12	-10000	0	-0.82	7	7
ADORA2A	-0.24	0.27	0.53	2	-0.74	43	45
germ cell development	-0.3	0.34	-10000	0	-0.74	142	142
SLC11A2	-0.22	0.27	-10000	0	-0.74	41	41
BHLHE40	-0.23	0.26	-10000	0	-0.75	40	40
HIF1AN	0.022	0.023	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.21	0.2	-10000	0	-0.48	78	78
ETS1	0.045	0.012	-10000	0	-10000	0	0
CITED2	-0.035	0.17	-10000	0	-0.74	23	23
KDR	0.009	0.098	-10000	0	-0.86	5	5
PGK1	-0.23	0.27	-10000	0	-0.75	41	41
SIRT1	0.028	0.006	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	-0.26	0.32	-10000	0	-0.89	44	44
EPAS1	-0.19	0.14	0.33	1	-0.36	108	109
SP1	0.035	0.015	-10000	0	-10000	0	0
ABCG2	-0.23	0.27	-10000	0	-0.75	43	43
EFNA1	-0.22	0.27	-10000	0	-0.74	42	42
FXN	-0.24	0.27	0.56	1	-0.74	43	44
POU5F1	-0.32	0.35	-10000	0	-0.78	144	144
neuron apoptosis	0.25	0.31	0.86	44	-10000	0	44
EP300	0.028	0.029	-10000	0	-0.64	1	1
EGLN3	-0.53	0.21	-10000	0	-0.6	462	462
EGLN2	0.025	0.018	-10000	0	-10000	0	0
EGLN1	0.021	0.022	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.037	0.044	-10000	0	-0.38	3	3
VHL	0.021	0.02	-10000	0	-0.32	1	1
ARNT	0.02	0.023	-10000	0	-10000	0	0
SLC2A1	-0.25	0.29	0.5	1	-0.82	50	51
TWIST1	-0.23	0.26	0.56	1	-0.72	46	47
ELK1	0.037	0.007	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.17	0.18	-10000	0	-0.5	23	23
VEGFA	-0.34	0.36	-10000	0	-0.78	150	150
CREBBP	0.029	0.006	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0.008	0.041	0.17	2	-0.45	4	6
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.025	0.085	-10000	0	-0.46	15	15
STXBP1	0.028	0.029	-10000	0	-0.64	1	1
ACh/CHRNA1	-0.16	0.2	-10000	0	-0.39	220	220
RAB3GAP2/RIMS1/UNC13B	0.04	0.077	-10000	0	-0.39	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.007	0.11	-10000	0	-0.63	15	15
mol:ACh	0.002	0.046	0.1	43	-0.15	3	46
RAB3GAP2	0.029	0.007	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.019	0.087	-10000	0	-0.4	8	8
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.16	0.2	-10000	0	-0.39	220	220
UNC13B	0.029	0.006	-10000	0	-10000	0	0
CHRNA1	-0.23	0.3	-10000	0	-0.59	220	220
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.052	0.16	-10000	0	-0.43	82	82
SNAP25	-0.022	0.077	0.12	4	-0.21	74	78
VAMP2	0.007	0.001	-10000	0	-10000	0	0
SYT1	-0.074	0.24	-10000	0	-0.63	82	82
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.024	0.042	-10000	0	-0.38	5	5
STX1A/SNAP25 fragment 1/VAMP2	0.019	0.087	-10000	0	-0.4	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.03	0.041	-10000	0	-0.4	4	4
ARNO/beta Arrestin1-2	0.022	0.066	-10000	0	-0.78	1	1
EGFR	0.019	0.067	-10000	0	-0.6	6	6
EPHA2	0.027	0.03	-10000	0	-0.64	1	1
USP6	0.028	0.027	-10000	0	-0.59	1	1
IQSEC1	0.021	0.014	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.4	0.16	-10000	0	-0.48	425	425
ARRB2	-0.006	0.075	-10000	0	-0.26	40	40
mol:GTP	0.001	0.046	0.19	6	-0.18	4	10
ARRB1	0.03	0.003	-10000	0	-10000	0	0
FBXO8	0.029	0.004	-10000	0	-10000	0	0
TSHR	-0.043	0.2	-10000	0	-0.59	60	60
EGF	-0.57	0.2	-10000	0	-0.63	474	474
somatostatin receptor activity	0	0	0.001	16	-0.001	21	37
ARAP2	0.027	0.041	-10000	0	-0.64	2	2
mol:GDP	-0.046	0.099	0.25	5	-0.33	24	29
mol:PI-3-4-5-P3	0	0	0.001	8	-0.001	10	18
ITGA2B	0.007	0.12	-10000	0	-0.59	19	19
ARF6	0.028	0.008	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.065	0.041	-10000	0	-0.36	3	3
ADAP1	0.022	0.058	-10000	0	-0.64	4	4
KIF13B	0.027	0.009	-10000	0	-10000	0	0
HGF/MET	0.019	0.1	-10000	0	-0.47	20	20
PXN	0.029	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.065	0.11	0.29	11	-0.34	23	34
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.34	0.14	-10000	0	-0.4	422	422
ADRB2	0.02	0.043	-10000	0	-0.64	2	2
receptor agonist activity	0	0	0	19	0	15	34
actin filament binding	0	0	0.001	19	-0.001	23	42
SRC	0.029	0.006	-10000	0	-10000	0	0
ITGB3	0.023	0.065	-10000	0	-0.64	5	5
GNAQ	0.029	0.006	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	25	-0.001	13	38
ARF6/GDP	-0.049	0.12	0.27	5	-0.42	15	20
ARF6/GDP/GULP/ACAP1	-0.14	0.19	0.27	1	-0.43	89	90
alphaIIb/beta3 Integrin/paxillin/GIT1	0.055	0.09	-10000	0	-0.42	6	6
ACAP1	-0.21	0.3	-10000	0	-0.59	203	203
ACAP2	0.028	0.007	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	-0.007	0.1	-10000	0	-0.36	40	40
EFNA1	0.027	0.028	-10000	0	-0.59	1	1
HGF	0.003	0.12	-10000	0	-0.6	20	20
CYTH3	0.011	0.004	-10000	0	-10000	0	0
CYTH2	0.018	0.044	-10000	0	-0.99	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
fibronectin binding	0	0	0.001	31	-0.001	14	45
endosomal lumen acidification	0	0	0.001	3	-0.001	21	24
microtubule-based process	0	0	-10000	0	-0.001	1	1
GULP1	0.006	0.12	-10000	0	-0.62	18	18
GNAQ/ARNO	0.034	0.043	-10000	0	-0.92	1	1
mol:Phosphatidic acid	0	0	0	4	-10000	0	4
PIP3-E	0	0	0.001	2	0	1	3
MET	0.024	0.039	-10000	0	-0.59	2	2
GNA14	0.02	0.076	-10000	0	-0.64	7	7
GNA15	0.012	0.1	-10000	0	-0.59	15	15
GIT1	0.029	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	22	-0.001	16	38
GNA11	0.026	0.05	-10000	0	-0.64	3	3
LHCGR	-0.04	0.16	-10000	0	-0.59	39	39
AGTR1	-0.002	0.14	-10000	0	-0.62	25	25
desensitization of G-protein coupled receptor protein signaling pathway	-0.007	0.1	-10000	0	-0.36	40	40
IPCEF1/ARNO	-0.25	0.12	-10000	0	-0.64	6	6
alphaIIb/beta3 Integrin	0.021	0.1	-10000	0	-0.46	23	23

×

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	-0.024	0.046	-9999	-10000	0	0
NFATC2	-0.025	0.061	-9999	-0.45	5	5
NFATC3	-0.023	0.046	-9999	-10000	0	0
CD40LG	-0.27	0.34	-9999	-0.79	103	103
PTGS2	-0.26	0.31	-9999	-0.74	93	93
JUNB	0.027	0.041	-9999	-0.64	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.013	0.033	-9999	-10000	0	0
CaM/Ca2+	-0.013	0.033	-9999	-10000	0	0
CALM1	0.004	0.027	-9999	-10000	0	0
JUN	0.003	0.028	-9999	-10000	0	0
mol:Ca2+	-0.017	0.016	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.016	-9999	-10000	0	0
FOSL1	-0.001	0.13	-9999	-0.59	26	26
CREM	0.029	0.004	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.14	0.2	-9999	-0.6	28	28
FOS	-0.011	0.1	-9999	-0.64	12	12
IFNG	-0.36	0.4	-9999	-0.78	218	218
AP-1/NFAT1-c-4	-0.3	0.37	-9999	-0.87	98	98
FASLG	-0.37	0.4	-9999	-0.77	221	221
NFAT1-c-4/ICER1	-0.063	0.11	-9999	-0.46	5	5
IL2RA	-0.29	0.35	-9999	-0.82	109	109
FKBP12/FK506	0.021	0.004	-9999	-10000	0	0
CSF2	-0.25	0.3	-9999	-0.74	85	85
JunB/Fra1/NFAT1-c-4	-0.07	0.13	-9999	-0.48	11	11
IL4	-0.24	0.29	-9999	-0.72	82	82
IL2	-0.007	0.12	-9999	-0.86	7	7
IL3	-0.014	0.074	-9999	-0.69	1	1
FKBP1A	0.029	0.005	-9999	-10000	0	0
BATF3	-0.025	0.17	-9999	-0.59	45	45
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.029	0.007	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.028	0.011	-9999	-10000	0	0
SVIL	0.028	0.01	-9999	-10000	0	0
ZNF318	0.03	0.013	-9999	-10000	0	0
JMJD2C	-0.001	0.017	-9999	-0.086	18	18
T-DHT/AR/Ubc9	-0.084	0.093	-9999	-0.47	23	23
CARM1	0.03	0.003	-9999	-10000	0	0
PRDX1	0.029	0.006	-9999	-10000	0	0
PELP1	0.029	0.005	-9999	-10000	0	0
CTNNB1	0.02	0.015	-9999	-10000	0	0
AKT1	0.028	0.009	-9999	-10000	0	0
PTK2B	0.026	0.011	-9999	-10000	0	0
MED1	0.03	0.005	-9999	-10000	0	0
MAK	0.029	0.03	-9999	-0.59	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.02	0.06	-9999	-0.65	4	4
GSN	0.027	0.012	-9999	-10000	0	0
NCOA2	0.015	0.091	-9999	-0.64	10	10
NCOA6	0.027	0.011	-9999	-10000	0	0
DNA-PK	0.055	0.022	-9999	-10000	0	0
NCOA4	0.029	0.005	-9999	-10000	0	0
PIAS3	0.028	0.009	-9999	-10000	0	0
cell proliferation	-0.044	0.1	-9999	-0.54	19	19
XRCC5	0.029	0.007	-9999	-10000	0	0
UBE3A	0.027	0.015	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.099	0.12	-9999	-0.5	38	38
FHL2	-0.051	0.11	-9999	-0.74	9	9
RANBP9	0.028	0.011	-9999	-10000	0	0
JMJD1A	-0.12	0.052	-9999	-0.14	453	453
CDK6	0.025	0.03	-9999	-0.63	1	1
TGFB1I1	0.026	0.029	-9999	-0.59	1	1
T-DHT/AR/CyclinD1	-0.099	0.11	-9999	-0.46	42	42
XRCC6	0.03	0.005	-9999	-10000	0	0
T-DHT/AR	-0.16	0.1	-9999	-0.44	34	34
CTDSP1	0.028	0.007	-9999	-10000	0	0
CTDSP2	0.031	0.012	-9999	-10000	0	0
BRCA1	0.028	0.01	-9999	-10000	0	0
TCF4	0.03	0.009	-9999	-10000	0	0
CDKN2A	-0.57	0.13	-9999	-0.6	503	503
SRF	0.036	0.015	-9999	-10000	0	0
NKX3-1	-0.21	0.082	-9999	-0.24	465	465
KLK3	0.02	0.089	-9999	-0.45	12	12
TMF1	0.023	0.012	-9999	-10000	0	0
HNRNPA1	0.03	0.007	-9999	-10000	0	0
AOF2	-0.001	0.006	-9999	-0.049	1	1
APPL1	0.017	0.014	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.084	0.093	-9999	-0.46	24	24
AR	-0.083	0.14	-9999	-0.66	26	26
UBA3	0.023	0.012	-9999	-10000	0	0
PATZ1	0.03	0.007	-9999	-10000	0	0
PAWR	0.028	0.029	-9999	-0.64	1	1
PRKDC	0.028	0.008	-9999	-10000	0	0
PA2G4	0.03	0.008	-9999	-10000	0	0
UBE2I	0.029	0.006	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.076	0.086	-9999	-0.42	25	25
RPS6KA3	0.027	0.032	-9999	-0.66	1	1
T-DHT/AR/ARA70	-0.086	0.093	-9999	-0.46	24	24
LATS2	0.03	0.007	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.077	0.085	-9999	-0.42	25	25
Cyclin D3/CDK11 p58	0.021	0.005	-9999	-10000	0	0
VAV3	0.011	0.11	-9999	-0.64	14	14
KLK2	-0.078	0.096	-9999	-0.53	19	19
CASP8	0.029	0.006	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.077	0.11	-9999	-0.49	26	26
TMPRSS2	-0.86	0.33	-9999	-0.98	457	457
CCND1	0.008	0.11	-9999	-0.59	18	18
PIAS1	0.028	0.015	-9999	-10000	0	0
mol:T-DHT	-0.059	0.025	-9999	-0.069	444	444
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.027	0.02	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.079	0.096	-9999	-0.47	22	22
CMTM2	0.016	0.089	-9999	-0.59	11	11
SNURF	0.008	0.12	-9999	-0.64	17	17
ZMIZ1	-0.049	0.033	-9999	-10000	0	0
CCND3	0.029	0.006	-9999	-10000	0	0
TGIF1	0.03	0.007	-9999	-10000	0	0
FKBP4	0.027	0.011	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.028	0.008	-10000	0	-10000	0	0
VLDLR	0.029	0.006	-10000	0	-10000	0	0
LRPAP1	0.029	0.004	-10000	0	-10000	0	0
NUDC	0.029	0.006	-10000	0	-10000	0	0
RELN/LRP8	-0.087	0.21	-10000	0	-0.4	159	159
CaM/Ca2+	0.021	0.006	-10000	0	-10000	0	0
KATNA1	0.027	0.008	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.08	0.19	-10000	0	-0.36	158	158
IQGAP1/CaM	0.041	0.012	-10000	0	-10000	0	0
DAB1	0.01	0.096	-10000	0	-0.59	13	13
IQGAP1	0.03	0.004	-10000	0	-10000	0	0
PLA2G7	-0.44	0.27	-10000	0	-0.59	396	396
CALM1	0.028	0.008	-10000	0	-10000	0	0
DYNLT1	0.028	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.041	0.023	-10000	0	-0.43	1	1
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.029	0.005	-10000	0	-10000	0	0
CDK5R1	0.029	0.005	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	0.016	0.004	-10000	0	-10000	0	0
CDK5R2	-0.049	0.2	-10000	0	-0.6	63	63
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.099	0.21	-10000	0	-0.4	168	168
YWHAE	0.029	0.005	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.052	0.18	0.32	26	-0.46	13	39
MAP1B	0.008	0.007	-10000	0	-10000	0	0
RAC1	0.021	0.008	-10000	0	-10000	0	0
p35/CDK5	-0.071	0.16	-10000	0	-10000	0	0
RELN	-0.17	0.3	-10000	0	-0.63	158	158
PAFAH/LIS1	-0.27	0.18	-10000	0	-0.37	383	383
LIS1/CLIP170	0.037	0.011	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.052	0.13	-10000	0	-0.41	3	3
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.061	0.14	-10000	0	-0.43	14	14
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.085	0.16	-10000	0	-0.5	13	13
LIS1/IQGAP1	0.037	0.01	-10000	0	-10000	0	0
RHOA	0.016	0.011	-10000	0	-10000	0	0
PAFAH1B1	0.022	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.028	0.029	-10000	0	-0.64	1	1
PAFAH1B2	0.028	0.029	-10000	0	-0.64	1	1
MAP1B/LIS1/Dynein heavy chain	0.038	0.023	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.049	0.18	0.34	14	-0.46	10	24
LRP8	0.028	0.028	-10000	0	-0.59	1	1
NDEL1/Katanin 60	-0.055	0.18	0.32	24	-0.46	12	36
P39/CDK5	-0.1	0.19	-10000	0	-0.59	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.037	0.011	-10000	0	-10000	0	0
CDK5	-0.087	0.16	-10000	0	-10000	0	0
PPP2R5D	0.029	0.006	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.032	0.009	-10000	0	-10000	0	0
CSNK2A1	0.029	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.073	0.19	-10000	0	-0.35	149	149
RELN/VLDLR	-0.068	0.2	-10000	0	-0.36	158	158
CDC42	0.022	0.007	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.18	0.19	-10000	0	-0.58	32	32
IHH	-0.08	0.19	-10000	0	-0.69	44	44
SHH Np/Cholesterol/GAS1	0.004	0.098	-10000	0	-0.37	30	30
LRPAP1	0.029	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.004	0.097	0.37	30	-10000	0	30
SMO/beta Arrestin2	-0.085	0.15	-10000	0	-0.52	25	25
SMO	-0.096	0.15	-10000	0	-0.54	25	25
AKT1	-0.034	0.11	-10000	0	-0.54	10	10
ARRB2	0.028	0.032	-10000	0	-0.71	1	1
BOC	0.028	0.008	-10000	0	-10000	0	0
ADRBK1	0.03	0.003	-10000	0	-10000	0	0
heart looping	-0.094	0.14	-10000	0	-0.53	25	25
STIL	-0.069	0.13	-10000	0	-0.52	6	6
DHH N/PTCH2	0.008	0.12	-10000	0	-0.44	36	36
DHH N/PTCH1	-0.1	0.15	-10000	0	-0.5	32	32
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
DHH	0.014	0.099	-10000	0	-0.64	12	12
PTHLH	-0.28	0.27	-10000	0	-0.81	37	37
determination of left/right symmetry	-0.094	0.14	-10000	0	-0.53	25	25
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
skeletal system development	-0.28	0.27	-10000	0	-0.8	37	37
IHH N/Hhip	-0.16	0.25	-10000	0	-0.53	156	156
DHH N/Hhip	-0.093	0.23	-10000	0	-0.48	133	133
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.094	0.14	-10000	0	-0.53	25	25
pancreas development	-0.13	0.28	-10000	0	-0.62	130	130
HHAT	0.029	0.006	-10000	0	-10000	0	0
PI3K	0.037	0.035	-10000	0	-0.47	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.008	0.15	-10000	0	-0.58	32	32
somite specification	-0.094	0.14	-10000	0	-0.53	25	25
SHH Np/Cholesterol/PTCH1	-0.082	0.13	-10000	0	-0.44	26	26
SHH Np/Cholesterol/PTCH2	0.007	0.091	-10000	0	-0.34	31	31
SHH Np/Cholesterol/Megalin	-0.004	0.12	-10000	0	-0.4	36	36
SHH	0.011	0.068	-10000	0	-0.47	10	10
catabolic process	-0.12	0.16	-10000	0	-0.52	32	32
SMO/Vitamin D3	-0.084	0.14	-10000	0	-0.49	26	26
SHH Np/Cholesterol/Hhip	-0.068	0.18	-10000	0	-0.38	116	116
LRP2	-0.022	0.17	-10000	0	-0.59	43	43
receptor-mediated endocytosis	-0.096	0.16	-10000	0	-0.65	17	17
SHH Np/Cholesterol/BOC	0.022	0.056	-10000	0	-0.36	10	10
SHH Np/Cholesterol/CDO	-0.015	0.12	-10000	0	-0.34	61	61
mesenchymal cell differentiation	0.068	0.17	0.38	116	-10000	0	116
mol:Vitamin D3	-0.076	0.14	-10000	0	-0.45	26	26
IHH N/PTCH2	-0.057	0.16	-10000	0	-0.46	67	67
CDON	-0.04	0.2	-10000	0	-0.59	59	59
IHH N/PTCH1	-0.12	0.16	-10000	0	-0.53	32	32
Megalin/LRPAP1	0.004	0.13	-10000	0	-0.47	35	35
PTCH2	-0.001	0.13	-10000	0	-0.59	25	25
SHH Np/Cholesterol	0.011	0.053	-10000	0	-0.37	10	10
PTCH1	-0.12	0.16	-10000	0	-0.52	32	32
HHIP	-0.13	0.28	-10000	0	-0.62	130	130

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.039	0.015	-10000	0	-10000	0	0
VLDLR	0.029	0.006	-10000	0	-10000	0	0
CRKL	0.03	0.004	-10000	0	-10000	0	0
LRPAP1	0.029	0.004	-10000	0	-10000	0	0
FYN	0.028	0.008	-10000	0	-10000	0	0
ITGA3	0.028	0.027	-10000	0	-0.59	1	1
RELN/VLDLR/Fyn	-0.087	0.21	-10000	0	-0.4	158	158
MAPK8IP1/MKK7/MAP3K11/JNK1	0.079	0.05	-10000	0	-0.68	1	1
AKT1	-0.065	0.13	-10000	0	-0.38	15	15
MAP2K7	0.03	0.003	-10000	0	-10000	0	0
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0
DAB1	0.01	0.096	-10000	0	-0.59	13	13
RELN/LRP8/DAB1	-0.089	0.2	-10000	0	-0.37	169	169
LRPAP1/LRP8	0.041	0.023	-10000	0	-0.43	1	1
RELN/LRP8/DAB1/Fyn	-0.075	0.19	-10000	0	-0.35	162	162
DAB1/alpha3/beta1 Integrin	-0.064	0.18	-10000	0	-0.6	1	1
long-term memory	-0.11	0.21	-10000	0	-0.62	19	19
DAB1/LIS1	-0.059	0.19	-10000	0	-0.62	1	1
DAB1/CRLK/C3G	-0.065	0.18	-10000	0	-0.6	1	1
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
DAB1/NCK2	-0.059	0.19	-10000	0	-0.62	1	1
ARHGEF2	0.028	0.007	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.053	0.21	-10000	0	-0.6	68	68
CDK5R1	0.029	0.005	-10000	0	-10000	0	0
RELN	-0.17	0.3	-10000	0	-0.63	158	158
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
RELN/LRP8/Fyn	-0.087	0.21	-10000	0	-0.4	159	159
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.11	0.22	-10000	0	-0.64	20	20
MAPK8	0.027	0.041	-10000	0	-0.64	2	2
RELN/VLDLR/DAB1	-0.089	0.2	-10000	0	-0.37	168	168
ITGB1	0.029	0.004	-10000	0	-10000	0	0
MAP1B	-0.087	0.18	-10000	0	-0.35	130	130
RELN/LRP8	-0.087	0.21	-10000	0	-0.4	159	159
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.066	0.2	-10000	0	-0.38	28	28
PI3K	0.037	0.035	-10000	0	-0.47	2	2
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.042	0.022	-10000	0	-0.43	1	1
RAP1A	-0.056	0.18	0.44	5	-0.57	1	6
PAFAH1B1	0.029	0.005	-10000	0	-10000	0	0
MAPK8IP1	0.027	0.041	-10000	0	-0.64	2	2
CRLK/C3G	0.043	0.009	-10000	0	-10000	0	0
GRIN2B	0.023	0.039	-10000	0	-0.59	2	2
NCK2	0.029	0.006	-10000	0	-10000	0	0
neuron differentiation	-0.034	0.13	-10000	0	-0.4	24	24
neuron adhesion	-0.048	0.17	0.4	8	-0.54	1	9
LRP8	0.028	0.028	-10000	0	-0.59	1	1
GSK3B	-0.059	0.12	-10000	0	-0.52	2	2
RELN/VLDLR/DAB1/Fyn	-0.075	0.19	-10000	0	-0.35	168	168
MAP3K11	0.029	0.029	-10000	0	-0.64	1	1
RELN/VLDLR/DAB1/P13K	-0.069	0.14	-10000	0	-0.29	143	143
CDK5	0.027	0.009	-10000	0	-10000	0	0
MAPT	0.012	0.096	0.71	5	-0.59	6	11
neuron migration	-0.066	0.18	0.46	4	-0.52	2	6
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.034	0.13	-10000	0	-0.4	24	24
RELN/VLDLR	-0.068	0.2	-10000	0	-0.36	158	158

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.054	-10000	0	-0.59	4	4
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.059	0.15	0.44	29	-0.35	1	30
IL27/IL27R/JAK1	-0.027	0.27	0.67	3	-0.69	31	34
TBX21	-0.14	0.34	0.57	9	-0.63	112	121
IL12B	-0.046	0.19	-10000	0	-0.6	54	54
IL12A	0.007	0.01	-10000	0	-10000	0	0
IL6ST	-0.005	0.12	-10000	0	-0.63	18	18
IL27RA/JAK1	0.013	0.063	-10000	0	-0.44	1	1
IL27	-0.022	0.15	-10000	0	-0.6	32	32
TYK2	0.011	0.026	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.011	0.11	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.059	0.15	0.44	29	-0.35	1	30
T cell proliferation during immune response	0.059	0.15	0.44	29	-0.35	1	30
MAPKKK cascade	-0.059	0.15	0.35	1	-0.44	29	30
STAT3	0.029	0.004	-10000	0	-10000	0	0
STAT2	0.029	0.005	-10000	0	-10000	0	0
STAT1	0.029	0.029	-10000	0	-0.59	1	1
IL12RB1	-0.16	0.29	-10000	0	-0.6	159	159
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.1	0.3	0.56	9	-0.59	78	87
IL27/IL27R/JAK2/TYK2	-0.059	0.15	0.36	1	-0.45	28	29
positive regulation of T cell mediated cytotoxicity	-0.059	0.15	0.35	1	-0.44	29	30
STAT1 (dimer)	0.018	0.42	0.54	108	-0.74	59	167
JAK2	0.015	0.021	-10000	0	-10000	0	0
JAK1	0.03	0.009	-10000	0	-10000	0	0
STAT2 (dimer)	-0.039	0.15	0.39	2	-0.44	18	20
T cell proliferation	-0.088	0.17	-10000	0	-0.53	31	31
IL12/IL12R/TYK2/JAK2	-0.099	0.17	-10000	0	-0.8	3	3
IL17A	-0.011	0.11	-10000	0	-10000	0	0
mast cell activation	0.059	0.15	0.44	29	-0.35	1	30
IFNG	-0.027	0.056	0.14	4	-0.1	50	54
T cell differentiation	-0.008	0.01	0.02	4	-0.023	116	120
STAT3 (dimer)	-0.04	0.16	0.39	2	-0.47	11	13
STAT5A (dimer)	-0.04	0.16	0.39	2	-0.44	19	21
STAT4 (dimer)	-0.058	0.18	0.39	2	-0.52	39	41
STAT4	-0.007	0.14	-10000	0	-0.59	30	30
T cell activation	-0.009	0.006	0.07	1	-10000	0	1
IL27R/JAK2/TYK2	-0.012	0.11	-10000	0	-0.47	5	5
GATA3	-0.6	0.65	0.5	1	-1.3	258	259
IL18	0.007	0.044	-10000	0	-0.44	5	5
positive regulation of mast cell cytokine production	-0.04	0.15	0.38	2	-0.46	11	13
IL27/EBI3	-0.066	0.22	-10000	0	-0.55	86	86
IL27RA	-0.004	0.049	-10000	0	-0.47	1	1
IL6	-0.047	0.2	-10000	0	-0.61	62	62
STAT5A	0.029	0.004	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	-0.011	0.057	-10000	0	-10000	0	0
IL1B	0.005	0.048	-10000	0	-0.44	6	6
EBI3	-0.068	0.22	-10000	0	-0.61	76	76
TNF	0.003	0.057	-10000	0	-0.46	8	8

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.012	0.13	-9999	-0.42	46	46
EFNA5	-0.026	0.18	-9999	-0.63	40	40
FYN	0.007	0.14	-9999	-0.38	46	46
neuron projection morphogenesis	-0.012	0.13	-9999	-0.42	46	46
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.012	0.13	-9999	-0.42	46	46
EPHA5	0.012	0.077	-9999	-0.6	8	8

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.14	0.26	-10000	0	-0.7	76	76
NFATC2	-0.075	0.21	-10000	0	-0.73	14	14
NFATC3	-0.019	0.066	-10000	0	-0.34	1	1
CD40LG	-0.19	0.35	-10000	0	-0.95	47	47
ITCH	0.041	0.046	-10000	0	-10000	0	0
CBLB	0.038	0.047	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.33	0.44	-10000	0	-0.98	120	120
JUNB	0.027	0.041	-10000	0	-0.64	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.038	0.055	-10000	0	-0.3	11	11
T cell anergy	0.025	0.073	-10000	0	-0.41	10	10
TLE4	-0.038	0.15	-10000	0	-0.57	11	11
Jun/NFAT1-c-4/p21SNFT	-0.13	0.28	-10000	0	-0.93	15	15
AP-1/NFAT1-c-4	-0.18	0.35	-10000	0	-1.1	22	22
IKZF1	-0.094	0.25	-10000	0	-0.62	88	88
T-helper 2 cell differentiation	-0.28	0.26	0.5	2	-0.68	67	69
AP-1/NFAT1	-0.052	0.17	-10000	0	-0.59	13	13
CALM1	0.037	0.034	-10000	0	-10000	0	0
EGR2	-0.091	0.24	-10000	0	-1.3	9	9
EGR3	-0.092	0.23	-10000	0	-1.3	9	9
NFAT1/FOXP3	-0.18	0.32	-10000	0	-0.71	110	110
EGR1	0.012	0.086	-10000	0	-0.63	9	9
JUN	0.011	0.032	-10000	0	-10000	0	0
EGR4	0.02	0.061	-10000	0	-0.59	5	5
mol:Ca2+	0	0.039	-10000	0	-0.45	1	1
GBP3	-0.04	0.16	-10000	0	-0.63	11	11
FOSL1	-0.001	0.13	-10000	0	-0.59	26	26
NFAT1-c-4/MAF/IRF4	-0.14	0.31	-10000	0	-0.84	23	23
DGKA	-0.039	0.16	-10000	0	-0.7	11	11
CREM	0.029	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.1	0.22	-10000	0	-1	7	7
CTLA4	-0.29	0.4	-10000	0	-0.71	232	232
NFAT1-c-4 (dimer)/EGR1	-0.084	0.24	-10000	0	-1.1	8	8
NFAT1-c-4 (dimer)/EGR4	-0.09	0.24	-10000	0	-1	8	8
FOS	-0.005	0.1	-10000	0	-0.63	12	12
IFNG	-0.28	0.36	-10000	0	-0.78	127	127
T cell activation	-0.045	0.18	-10000	0	-0.72	7	7
MAF	0.029	0.006	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.059	0.16	0.79	5	-10000	0	5
TNF	-0.066	0.23	-10000	0	-1.1	7	7
FASLG	-0.21	0.34	-10000	0	-1.3	11	11
TBX21	-0.21	0.31	-10000	0	-0.64	172	172
BATF3	-0.024	0.17	-10000	0	-0.59	45	45
PRKCQ	-0.026	0.1	-10000	0	-0.57	15	15
PTPN1	-0.037	0.15	-10000	0	-0.57	11	11
NFAT1-c-4/ICER1	-0.088	0.23	-10000	0	-0.97	8	8
GATA3	-0.3	0.33	-10000	0	-0.63	258	258
T-helper 1 cell differentiation	-0.27	0.35	-10000	0	-0.75	134	134
IL2RA	-0.23	0.36	-10000	0	-0.86	95	95
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.037	0.15	-10000	0	-0.57	11	11
E2F1	-0.028	0.19	-10000	0	-0.58	54	54
PPARG	0.021	0.014	-10000	0	-10000	0	0
SLC3A2	-0.037	0.15	-10000	0	-0.58	10	10
IRF4	-0.11	0.26	-10000	0	-0.59	118	118
PTGS2	-0.18	0.32	-10000	0	-1	22	22
CSF2	-0.17	0.3	-10000	0	-1	20	20
JunB/Fra1/NFAT1-c-4	-0.087	0.24	-10000	0	-0.96	8	8
IL4	-0.29	0.26	0.55	1	-0.72	63	64
IL5	-0.16	0.29	-10000	0	-0.97	17	17
IL2	-0.046	0.18	-10000	0	-0.73	7	7
IL3	-0.03	0.057	-10000	0	-0.9	1	1
RNF128	0.028	0.12	-10000	0	-0.63	16	16
NFATC1	-0.058	0.16	-10000	0	-0.84	4	4
CDK4	0.041	0.13	-10000	0	-10000	0	0
PTPRK	-0.042	0.15	-10000	0	-0.62	10	10
IL8	-0.18	0.33	-10000	0	-1	29	29
POU2F1	0.029	0.007	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.037	0.069	0.14	141	-0.14	2	143
BUB1B	-0.006	0.085	0.2	8	-0.31	27	35
PLK1	-0.004	0.047	0.15	10	-0.15	10	20
PLK1S1	0.007	0.031	0.15	9	-0.2	1	10
KIF2A	0.014	0.086	0.25	42	-0.33	4	46
regulation of mitotic centrosome separation	-0.004	0.047	0.15	10	-0.15	10	20
GOLGA2	0.029	0.006	-10000	0	-10000	0	0
Hec1/SPC24	-0.074	0.22	-10000	0	-0.45	122	122
WEE1	0.012	0.058	0.23	4	-0.85	1	5
cytokinesis	-0.054	0.17	0.26	12	-0.31	105	117
PP2A-alpha B56	-0.024	0.12	-10000	0	-0.6	7	7
AURKA	0.005	0.033	0.14	6	-0.17	5	11
PICH/PLK1	-0.014	0.11	-10000	0	-0.52	18	18
CENPE	-0.041	0.13	0.27	3	-0.39	62	65
RhoA/GTP	0.016	0.01	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.014	0.085	0.25	42	-0.33	4	46
PPP2CA	0.023	0.013	-10000	0	-10000	0	0
FZR1	0.028	0.029	-10000	0	-0.64	1	1
TPX2	-0.018	0.074	0.15	13	-0.15	107	120
PAK1	0.03	0.003	-10000	0	-10000	0	0
SPC24	-0.033	0.19	-10000	0	-0.59	53	53
FBXW11	0.023	0.013	-10000	0	-10000	0	0
CLSPN	-0.017	0.076	0.16	1	-0.2	59	60
GORASP1	0.021	0.014	-10000	0	-10000	0	0
metaphase	-0.002	0.006	0.017	20	-0.012	100	120
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.003	0.026	0.085	11	-0.077	10	21
G2 phase of mitotic cell cycle	0	0.002	0.017	2	-0.011	1	3
STAG2	0.03	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.11	0.22	-10000	0	-0.45	145	145
spindle elongation	-0.004	0.047	0.15	10	-0.15	10	20
ODF2	0.029	0.006	-10000	0	-10000	0	0
BUB1	-0.056	0.12	-10000	0	-0.66	7	7
TPT1	0.002	0.039	0.15	4	-0.19	11	15
CDC25C	-0.03	0.11	0.17	7	-0.2	93	100
CDC25B	0.025	0.055	-10000	0	-0.6	4	4
SGOL1	-0.038	0.069	0.14	2	-0.14	141	143
RHOA	0.021	0.014	-10000	0	-10000	0	0
CCNB1/CDK1	0.017	0.071	-10000	0	-0.43	8	8
CDC14B	0.011	0.003	-10000	0	-10000	0	0
CDC20	-0.022	0.17	-10000	0	-0.6	43	43
PLK1/PBIP1	-0.013	0.079	0.14	2	-0.37	18	20
mitosis	-0.002	0.003	0.025	2	-10000	0	2
FBXO5	-0.001	0.046	0.2	6	-0.21	3	9
CDC2	0	0.003	-10000	0	-0.017	8	8
NDC80	-0.099	0.25	-10000	0	-0.59	109	109
metaphase plate congression	-0.004	0.061	0.14	3	-0.25	22	25
ERCC6L	-0.001	0.1	-10000	0	-0.5	18	18
NLP/gamma Tubulin	-0.001	0.031	0.12	7	-0.12	8	15
microtubule cytoskeleton organization	0.002	0.039	0.14	4	-0.19	11	15
G2/M transition DNA damage checkpoint	0	0.002	0.012	2	-10000	0	2
PPP1R12A	0.03	0.005	-10000	0	-10000	0	0
interphase	0	0.002	0.012	2	-10000	0	2
PLK1/PRC1-2	-0.088	0.2	-10000	0	-0.35	176	176
GRASP65/GM130/RAB1/GTP/PLK1	0.02	0.046	-10000	0	-10000	0	0
RAB1A	0.029	0.005	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.001	0.034	0.12	13	-0.13	8	21
mitotic prometaphase	-0.002	0.005	0.017	17	-0.012	1	18
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.057	-10000	0	-0.49	3	3
microtubule-based process	-0.11	0.18	0.21	1	-0.36	176	177
Golgi organization	-0.004	0.047	0.15	10	-0.15	10	20
Cohesin/SA2	0.008	0.046	0.17	3	-10000	0	3
PPP1CB/MYPT1	0.042	0.011	-10000	0	-10000	0	0
KIF20A	-0.18	0.29	-10000	0	-0.59	176	176
APC/C/CDC20	-0.016	0.12	0.18	4	-0.39	43	47
PPP2R1A	0.03	0.003	-10000	0	-10000	0	0
chromosome segregation	-0.013	0.078	0.14	2	-0.37	18	20
PRC1	0.024	0.06	-10000	0	-0.59	5	5
ECT2	0.004	0.056	0.24	14	-10000	0	14
C13orf34	-0.001	0.036	0.12	11	-0.13	7	18
NUDC	-0.004	0.061	0.14	3	-0.25	22	25
regulation of attachment of spindle microtubules to kinetochore	-0.006	0.084	0.2	8	-0.3	27	35
spindle assembly	-0.002	0.04	0.14	10	-0.13	7	17
spindle stabilization	0.007	0.031	0.15	9	-0.2	1	10
APC/C/HCDH1	0.029	0.02	-10000	0	-0.41	1	1
MKLP2/PLK1	-0.11	0.18	0.21	1	-0.36	176	177
CCNB1	0.018	0.077	-10000	0	-0.59	8	8
PPP1CB	0.03	0.005	-10000	0	-10000	0	0
BTRC	0.029	0.006	-10000	0	-10000	0	0
ROCK2	-0.022	0.077	0.2	1	-0.38	10	11
TUBG1	0.004	0.037	0.16	3	-0.23	6	9
G2/M transition of mitotic cell cycle	-0.009	0.06	-10000	0	-0.42	8	8
MLF1IP	-0.006	0.084	-10000	0	-0.45	18	18
INCENP	0.028	0.003	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.01	0.018	-10000	0	-0.41	1	1
ADCY5	-0.005	0.079	-10000	0	-0.41	19	19
ADCY6	0.01	0.034	-10000	0	-0.76	1	1
ADCY7	-0.001	0.066	-10000	0	-0.37	16	16
ADCY1	0.001	0.062	-10000	0	-0.4	12	12
ADCY2	-0.067	0.16	-10000	0	-0.37	114	114
ADCY3	0.011	0.018	-10000	0	-0.41	1	1
ADCY8	-0.1	0.18	-10000	0	-0.37	156	156
PRKCE	0.011	0.021	-10000	0	-0.48	1	1
ADCY9	0.01	0.018	-10000	0	-0.41	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.042	0.13	0.29	20	-0.32	41	61

×

IL2 signaling events mediated by STAT5

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
GAB2	0.03	0.003	-10000	0	-10000	0	0
ELF1	-0.023	0.12	-10000	0	-0.53	4	4
CCNA2	-0.09	0.24	-10000	0	-0.59	101	101
PIK3CA	0.028	0.03	-10000	0	-0.64	1	1
JAK3	-0.093	0.25	-10000	0	-0.59	105	105
PIK3R1	0.027	0.03	-10000	0	-0.64	1	1
JAK1	0.029	0.006	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.052	0.16	-10000	0	-0.48	34	34
SHC1	0.029	0.007	-10000	0	-10000	0	0
SP1	0.036	0.019	-10000	0	-10000	0	0
IL2RA	-0.075	0.21	-10000	0	-0.51	102	102
IL2RB	-0.29	0.31	-10000	0	-0.59	272	272
SOS1	0.03	0.005	-10000	0	-10000	0	0
IL2RG	-0.01	0.15	-10000	0	-0.59	34	34
G1/S transition of mitotic cell cycle	-0.001	0.13	0.43	7	-0.53	4	11
PTPN11	0.03	0.006	-10000	0	-10000	0	0
CCND2	0.028	0.034	-10000	0	-0.51	2	2
LCK	0.003	0.12	-10000	0	-0.59	22	22
GRB2	0.03	0.005	-10000	0	-10000	0	0
IL2	0.014	0.084	-10000	0	-0.59	10	10
CDK6	0.025	0.03	-10000	0	-0.64	1	1
CCND3	-0.036	0.14	0.5	1	-0.6	1	2

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.042	0.024	-10000	0	-0.47	1	1
Necdin/E2F1	-0.008	0.15	-10000	0	-0.43	56	56
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.023	0.15	-10000	0	-0.62	7	7
NGF (dimer)/p75(NTR)/BEX1	-0.17	0.25	-10000	0	-0.43	245	245
NT-4/5 (dimer)/p75(NTR)	0.002	0.13	-10000	0	-0.45	38	38
IKBKB	0.028	0.008	-10000	0	-10000	0	0
AKT1	-0.009	0.15	0.41	4	-0.62	8	12
IKBKG	0.03	0.004	-10000	0	-10000	0	0
BDNF	-0.052	0.21	-10000	0	-0.59	69	69
MGDIs/NGR/p75(NTR)/LINGO1	0.009	0.14	-10000	0	-0.4	57	57
FURIN	0.03	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.025	0.18	-10000	0	-0.4	95	95
LINGO1	0.005	0.12	-10000	0	-0.59	21	21
Sortilin/TRAF6/NRIF	0.036	0.021	-10000	0	-10000	0	0
proBDNF (dimer)	-0.052	0.21	-10000	0	-0.59	69	69
NTRK1	-0.017	0.16	-10000	0	-0.61	37	37
RTN4R	0.022	0.067	-10000	0	-0.6	6	6
neuron apoptosis	-0.027	0.16	0.45	6	-0.55	12	18
IRAK1	0.03	0.003	-10000	0	-10000	0	0
SHC1	-0.033	0.15	-10000	0	-0.4	73	73
ARHGDIA	0.028	0.029	-10000	0	-0.64	1	1
RhoA/GTP	0.016	0.01	-10000	0	-10000	0	0
Gamma Secretase	0.079	0.029	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.011	0.16	-10000	0	-0.55	11	11
MAGEH1	0.03	0.003	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.009	0.16	-10000	0	-0.52	13	13
Mammalian IAPs/DIABLO	0.013	0.14	-10000	0	-0.33	75	75
proNGF (dimer)	-0.026	0.18	-10000	0	-0.59	47	47
MAGED1	0.03	0.003	-10000	0	-10000	0	0
APP	0.029	0.006	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.017	0.056	-10000	0	-0.62	4	4
ZNF274	0.03	0.003	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.019	0.14	-10000	0	-0.53	10	10
NGF	-0.027	0.18	-10000	0	-0.59	47	47
cell cycle arrest	0.012	0.17	0.36	10	-0.65	7	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.006	0.097	-10000	0	-0.4	16	16
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.022	0.11	-10000	0	-0.38	38	38
NCSTN	0.029	0.007	-10000	0	-10000	0	0
mol:GTP	-0.007	0.16	-10000	0	-0.4	73	73
PSENEN	0.03	0.003	-10000	0	-10000	0	0
mol:ceramide	-0.026	0.14	-10000	0	-0.54	11	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.009	0.068	-10000	0	-0.46	3	3
p75(NTR)/beta APP	0.011	0.12	-10000	0	-0.44	33	33
BEX1	-0.22	0.32	-10000	0	-0.63	193	193
mol:GDP	-0.045	0.15	-10000	0	-0.4	73	73
NGF (dimer)	-0.25	0.26	-10000	0	-0.44	300	300
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.026	0.14	-10000	0	-0.56	8	8
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
RAC1/GTP	-0.007	0.14	-10000	0	-0.35	67	67
MYD88	0.021	0.014	-10000	0	-10000	0	0
CHUK	0.029	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.006	0.16	-10000	0	-0.4	73	73
RHOB	0.029	0.005	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.007	0.14	-10000	0	-0.43	54	54
NT3 (dimer)	0.023	0.063	-10000	0	-0.62	5	5
TP53	-0.029	0.14	0.34	3	-0.59	7	10
PRDM4	-0.025	0.14	-10000	0	-0.57	10	10
BDNF (dimer)	-0.29	0.29	-10000	0	-0.48	340	340
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
SORT1	0.028	0.029	-10000	0	-0.64	1	1
activation of caspase activity	0.017	0.15	-10000	0	-0.61	7	7
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.011	0.16	-10000	0	-0.55	11	11
RHOC	0.029	0.006	-10000	0	-10000	0	0
XIAP	0.03	0.003	-10000	0	-10000	0	0
MAPK10	-0.013	0.15	0.46	7	-0.5	5	12
DIABLO	0.029	0.005	-10000	0	-10000	0	0
SMPD2	-0.027	0.14	-10000	0	-0.54	11	11
APH1B	0.03	0.003	-10000	0	-10000	0	0
APH1A	0.029	0.007	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.007	0.16	-10000	0	-0.4	74	74
PSEN1	0.028	0.008	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.041	0.012	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.006	0.13	-10000	0	-0.45	38	38
MAPK8	-0.014	0.14	0.43	7	-0.47	4	11
MAPK9	-0.018	0.13	0.45	6	-0.52	2	8
APAF1	0.029	0.005	-10000	0	-10000	0	0
NTF3	0.023	0.063	-10000	0	-0.62	5	5
NTF4	0.017	0.056	-10000	0	-0.62	4	4
NDN	0.027	0.041	-10000	0	-0.64	2	2
RAC1/GDP	0.02	0.007	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.003	0.14	-10000	0	-0.57	7	7
p75 CTF/Sortilin/TRAF6/NRIF	0.071	0.028	-10000	0	-0.37	1	1
RhoA-B-C/GTP	-0.007	0.16	-10000	0	-0.4	73	73
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.007	0.17	-10000	0	-0.55	10	10
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.006	0.17	-10000	0	-0.56	11	11
PRKACB	0.029	0.006	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.02	0.16	-10000	0	-0.43	68	68
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.064	0.22	-10000	0	-0.59	79	79
BIRC2	0.03	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	0.031	0.16	0.33	5	-0.53	7	12
BAD	0.004	0.15	0.48	10	-0.47	5	15
RIPK2	0.027	0.028	-10000	0	-0.59	1	1
NGFR	-0.011	0.16	-10000	0	-0.6	34	34
CYCS	-0.021	0.14	0.43	2	-0.62	8	10
ADAM17	0.029	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.008	0.16	-10000	0	-0.57	10	10
BCL2L11	0.005	0.15	0.46	10	-0.48	5	15
BDNF (dimer)/p75(NTR)	-0.049	0.2	-10000	0	-0.46	96	96
PI3K	0.005	0.16	-10000	0	-0.58	11	11
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.011	0.16	-10000	0	-0.55	11	11
NDNL2	0.03	0.003	-10000	0	-10000	0	0
YWHAE	0.029	0.005	-10000	0	-10000	0	0
PRKCI	0.028	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.029	0.18	-10000	0	-0.47	73	73
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.011	0.16	-10000	0	-0.55	11	11
TRAF6	0.03	0.003	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCZ	0.025	0.05	-10000	0	-0.64	3	3
PLG	-0.3	0.32	-10000	0	-0.61	270	270
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.048	0.16	-10000	0	-0.52	24	24
SQSTM1	0.022	0.013	-10000	0	-10000	0	0
NGFRAP1	0.03	0.003	-10000	0	-10000	0	0
CASP3	0.008	0.14	0.46	10	-0.44	5	15
E2F1	-0.035	0.19	-10000	0	-0.59	54	54
CASP9	0.029	0.006	-10000	0	-10000	0	0
IKK complex	0.021	0.13	-10000	0	-0.52	1	1
NGF (dimer)/TRKA	-0.035	0.18	-10000	0	-0.45	80	80
MMP7	-0.09	0.26	-10000	0	-0.63	95	95
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.024	0.15	-10000	0	-0.62	7	7
MMP3	-0.03	0.17	-10000	0	-0.59	46	46
APAF-1/Caspase 9	-0.053	0.13	-10000	0	-0.48	9	9

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.17	0.24	-10000	0	-0.43	234	234
PDGFRB	0.023	0.013	-10000	0	-10000	0	0
SPHK1	-0.01	0.082	-10000	0	-0.59	6	6
mol:S1P	-0.005	0.076	-10000	0	-0.5	6	6
S1P1/S1P/Gi	-0.054	0.13	0.32	1	-0.5	19	20
GNAO1	0.026	0.055	-10000	0	-0.6	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.029	0.11	0.33	1	-0.6	5	6
PLCG1	-0.043	0.12	0.32	2	-0.52	12	14
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.013	-10000	0	-10000	0	0
GNAI2	0.022	0.016	-10000	0	-10000	0	0
GNAI3	0.029	0.008	-10000	0	-10000	0	0
GNAI1	0.026	0.031	-10000	0	-0.65	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.16	0.19	-10000	0	-0.36	234	234
S1P1/S1P	-0.097	0.15	0.25	1	-0.38	28	29
negative regulation of cAMP metabolic process	-0.052	0.13	0.32	1	-0.49	19	20
MAPK3	-0.053	0.16	0.42	2	-0.62	23	25
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.01	-10000	0	-10000	0	0
KDR	0.029	0.029	-10000	0	-0.64	1	1
PLCB2	-0.11	0.18	0.32	9	-0.44	53	62
RAC1	0.027	0.009	-10000	0	-10000	0	0
RhoA/GTP	-0.092	0.12	-10000	0	-0.35	16	16
receptor internalization	-0.094	0.14	-10000	0	-0.35	29	29
PTGS2	-0.053	0.24	0.49	6	-0.96	25	31
Rac1/GTP	-0.085	0.12	-10000	0	-0.34	17	17
RHOA	0.021	0.014	-10000	0	-10000	0	0
VEGFA	-0.25	0.31	-10000	0	-0.59	234	234
negative regulation of T cell proliferation	-0.052	0.13	0.32	1	-0.49	19	20
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.026	0.051	-10000	0	-0.64	3	3
MAPK1	-0.056	0.16	0.32	1	-0.62	24	25
S1P1/S1P/PDGFB-D/PDGFRB	-0.087	0.14	0.3	1	-0.42	14	15
ABCC1	0.029	0.007	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.17	0.24	-10000	0	-0.44	234	234
alphaV beta3 Integrin	0.048	0.068	-10000	0	-0.44	9	9
PTK2	-0.093	0.17	0.57	4	-0.52	9	13
IGF1R	0.03	0.003	-10000	0	-10000	0	0
PI4KB	0.029	0.007	-10000	0	-10000	0	0
MFGE8	0.028	0.027	-10000	0	-0.59	1	1
SRC	0.029	0.006	-10000	0	-10000	0	0
CDKN1B	-0.042	0.18	-10000	0	-0.48	72	72
VEGFA	-0.25	0.31	-10000	0	-0.59	234	234
ILK	-0.043	0.18	-10000	0	-0.48	74	74
ROCK1	0.029	0.005	-10000	0	-10000	0	0
AKT1	-0.041	0.17	-10000	0	-0.46	68	68
PTK2B	-0.12	0.17	0.36	2	-0.5	2	4
alphaV/beta3 Integrin/JAM-A	0.002	0.15	-10000	0	-0.68	1	1
CBL	0.028	0.029	-10000	0	-0.64	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.15	0.22	-10000	0	-0.4	222	222
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.064	0.058	-10000	0	-0.37	4	4
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.096	0.16	-10000	0	-0.43	60	60
alphaV/beta3 Integrin/Syndecan-1	0.047	0.068	-10000	0	-0.4	11	11
PI4KA	0.03	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.026	0.12	-10000	0	-0.62	4	4
PI4 Kinase	0.042	0.011	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
alphaV/beta3 Integrin/Osteopontin	0.05	0.056	-10000	0	-0.4	7	7
RPS6KB1	0.018	0.13	0.47	13	-0.57	4	17
TLN1	0.029	0.006	-10000	0	-10000	0	0
MAPK3	0	0.11	-10000	0	-0.6	9	9
GPR124	0.025	0.039	-10000	0	-0.59	2	2
MAPK1	0.001	0.11	-10000	0	-0.6	9	9
PXN	0.029	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
alphaV/beta3 Integrin/Tumstatin	0.003	0.15	-10000	0	-0.42	57	57
cell adhesion	-0.11	0.18	-10000	0	-0.38	25	25
ANGPTL3	-0.27	0.32	-10000	0	-0.61	241	241
VEGFR2 homodimer/VEGFA homodimer/Src	-0.13	0.21	-10000	0	-0.37	231	231
IGF-1R heterotetramer	0.03	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
TGFBR2	0.022	0.014	-10000	0	-10000	0	0
ITGB3	0.023	0.065	-10000	0	-0.64	5	5
IGF1	0.023	0.06	-10000	0	-0.59	5	5
RAC1	0.027	0.009	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.047	0.053	-10000	0	-0.4	6	6
apoptosis	0.028	0.006	-10000	0	-10000	0	0
CD47	0.027	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.048	0.049	-10000	0	-0.4	5	5
VCL	0.029	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.036	0.087	-10000	0	-0.41	17	17
CSF1	0.028	0.029	-10000	0	-0.64	1	1
PIK3C2A	-0.045	0.19	-10000	0	-0.49	75	75
PI4 Kinase/Pyk2	-0.14	0.19	-10000	0	-0.56	43	43
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.2	-10000	0	-0.34	226	226
FAK1/Vinculin	-0.069	0.15	0.59	3	-0.47	4	7
alphaV beta3/Integrin/ppsTEM5	0.047	0.053	-10000	0	-0.4	6	6
RHOA	0.021	0.014	-10000	0	-10000	0	0
VTN	-0.069	0.24	-10000	0	-0.62	79	79
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
FGF2	0.023	0.064	-10000	0	-0.63	5	5
F11R	0.018	0.045	-10000	0	-0.47	4	4
alphaV/beta3 Integrin/Lactadherin	0.051	0.051	-10000	0	-0.4	6	6
alphaV/beta3 Integrin/TGFBR2	0.038	0.051	-10000	0	-0.4	5	5
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.067	0.046	-10000	0	-0.54	2	2
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.048	0.044	-10000	0	-0.37	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.017	0.16	-10000	0	-0.6	38	38
alphaV/beta3 Integrin/Pyk2	-0.11	0.18	-10000	0	-0.39	7	7
SDC1	0.021	0.071	-10000	0	-0.64	6	6
VAV3	0.03	0.084	0.36	7	-0.67	1	8
PTPN11	0.029	0.005	-10000	0	-10000	0	0
IRS1	0.023	0.058	-10000	0	-0.64	4	4
FAK1/Paxillin	-0.07	0.14	0.53	2	-0.5	3	5
cell migration	-0.063	0.13	0.52	2	-0.45	3	5
ITGAV	0.029	0.007	-10000	0	-10000	0	0
PI3K	0.012	0.14	-10000	0	-0.92	1	1
SPP1	0.026	0.05	-10000	0	-0.64	3	3
KDR	0.028	0.029	-10000	0	-0.64	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.029	0.007	-10000	0	-10000	0	0
COL4A3	-0.042	0.2	-10000	0	-0.61	58	58
angiogenesis	-0.008	0.14	0.32	4	-0.62	9	13
Rac1/GTP	0.035	0.065	-10000	0	-0.62	1	1
EDIL3	0.01	0.1	-10000	0	-0.6	14	14
cell proliferation	0.037	0.051	-10000	0	-0.4	5	5

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.18	0.36	-10000	0	-1.1	17	17
IL23A	-0.16	0.36	-10000	0	-1.2	10	10
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.36	-10000	0	-1	21	21
positive regulation of T cell mediated cytotoxicity	-0.19	0.39	-10000	0	-1.1	30	30
ITGA3	-0.16	0.36	-10000	0	-1.1	11	11
IL17F	-0.11	0.28	0.58	4	-0.73	12	16
IL12B	-0.057	0.19	-10000	0	-0.61	54	54
STAT1 (dimer)	-0.18	0.37	-10000	0	-1	28	28
CD4	-0.17	0.37	-10000	0	-1.1	16	16
IL23	-0.19	0.34	-10000	0	-1.1	15	15
IL23R	-0.021	0.16	-10000	0	-0.71	14	14
IL1B	-0.17	0.37	-10000	0	-1.1	14	14
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.17	0.36	-10000	0	-1	17	17
TYK2	0.014	0.035	-10000	0	-10000	0	0
STAT4	-0.007	0.14	-10000	0	-0.59	30	30
STAT3	0.029	0.005	-10000	0	-10000	0	0
IL18RAP	-0.14	0.27	-10000	0	-0.6	136	136
IL12RB1	-0.17	0.3	-10000	0	-0.62	159	159
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
IL12Rbeta1/TYK2	-0.12	0.24	-10000	0	-0.47	159	159
IL23R/JAK2	-0.024	0.16	-10000	0	-0.76	8	8
positive regulation of chronic inflammatory response	-0.19	0.39	-10000	0	-1.1	30	30
natural killer cell activation	0.002	0.01	0.049	10	-10000	0	10
JAK2	0.01	0.042	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
NFKB1	0.028	0.029	-10000	0	-0.63	1	1
RELA	0.029	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.19	0.33	-10000	0	-1.1	15	15
ALOX12B	-0.21	0.38	-10000	0	-1.1	21	21
CXCL1	-0.2	0.41	-10000	0	-1.2	34	34
T cell proliferation	-0.19	0.39	-10000	0	-1.1	30	30
NFKBIA	0.028	0.008	-10000	0	-10000	0	0
IL17A	-0.079	0.23	0.4	1	-0.6	4	5
PI3K	-0.17	0.36	-10000	0	-1	26	26
IFNG	-0.04	0.059	0.12	6	-0.12	23	29
STAT3 (dimer)	-0.16	0.35	-10000	0	-1	21	21
IL18R1	0.012	0.074	-10000	0	-0.61	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	-0.11	0.28	-10000	0	-0.74	20	20
IL18/IL18R	-0.095	0.2	-10000	0	-0.4	144	144
macrophage activation	-0.014	0.015	-10000	0	-10000	0	0
TNF	-0.17	0.37	-10000	0	-1.2	15	15
STAT3/STAT4	-0.18	0.38	-10000	0	-1	34	34
STAT4 (dimer)	-0.2	0.39	-10000	0	-1.1	35	35
IL18	0.015	0.061	-10000	0	-0.59	5	5
IL19	-0.17	0.36	-10000	0	-1.1	14	14
STAT5A (dimer)	-0.18	0.38	-10000	0	-1	29	29
STAT1	0.027	0.028	-10000	0	-0.59	1	1
SOCS3	0.024	0.054	-10000	0	-0.59	4	4
CXCL9	-0.26	0.43	-10000	0	-1	46	46
MPO	-0.18	0.36	-10000	0	-1.1	15	15
positive regulation of humoral immune response	-0.19	0.39	-10000	0	-1.1	30	30
IL23/IL23R/JAK2/TYK2	-0.2	0.39	-10000	0	-1.1	29	29
IL6	-0.2	0.44	-10000	0	-1.2	41	41
STAT5A	0.029	0.004	-10000	0	-10000	0	0
IL2	-0.011	0.086	-10000	0	-0.59	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.01	0.049	10	-10000	0	10
CD3E	-0.25	0.43	-10000	0	-1	46	46
keratinocyte proliferation	-0.19	0.39	-10000	0	-1.1	30	30
NOS2	-0.17	0.36	-10000	0	-1.1	16	16

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.022	0.15	0.37	13	-0.44	11	24
IKBKB	0.006	0.12	0.33	19	-0.31	5	24
AKT1	0.001	0.14	0.41	24	-0.29	4	28
IKBKG	0.02	0.11	0.32	15	-0.3	1	16
CALM1	-0.003	0.09	0.36	1	-10000	0	1
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
MAP3K1	-0.045	0.19	0.41	16	-0.47	33	49
MAP3K7	0.028	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.005	0.095	-10000	0	-0.32	7	7
DOK1	0.029	0.005	-10000	0	-10000	0	0
AP-1	0.013	0.11	0.29	24	-0.28	6	30
LYN	0.028	0.007	-10000	0	-10000	0	0
BLNK	0.028	0.03	-10000	0	-0.64	1	1
SHC1	0.029	0.007	-10000	0	-10000	0	0
BCR complex	-0.075	0.21	-10000	0	-0.44	126	126
CD22	-0.064	0.16	-10000	0	-0.5	28	28
CAMK2G	0.003	0.088	0.35	1	-10000	0	1
CSNK2A1	0.029	0.005	-10000	0	-10000	0	0
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
SHC/GRB2/SOS1	-0.041	0.14	-10000	0	-0.55	3	3
GO:0007205	-0.005	0.096	-10000	0	-0.33	7	7
SYK	0.027	0.033	-10000	0	-0.48	2	2
ELK1	0	0.095	0.3	1	-10000	0	1
NFATC1	-0.038	0.15	0.37	7	-0.39	28	35
B-cell antigen/BCR complex	-0.075	0.21	-10000	0	-0.44	126	126
PAG1/CSK	0.041	0.011	-10000	0	-10000	0	0
NFKBIB	0.021	0.053	0.14	28	-0.13	5	33
HRAS	-0.003	0.094	0.31	2	-0.33	2	4
NFKBIA	0.021	0.052	0.14	28	-0.13	4	32
NF-kappa-B/RelA/I kappa B beta	0.027	0.049	0.16	18	-0.17	1	19
RasGAP/Csk	-0.079	0.23	-10000	0	-0.62	46	46
mol:GDP	-0.003	0.092	0.26	1	-0.34	5	6
PTEN	0.029	0.006	-10000	0	-10000	0	0
CD79B	0.026	0.047	-10000	0	-0.59	3	3
NF-kappa-B/RelA/I kappa B alpha	0.027	0.048	0.16	18	-0.17	1	19
GRB2	0.029	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.014	0.18	0.4	14	-0.45	16	30
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:IP3	-0.007	0.094	-10000	0	-0.33	7	7
CSK	0.03	0.003	-10000	0	-10000	0	0
FOS	-0.005	0.1	0.32	3	-0.52	3	6
CHUK	0.012	0.12	0.32	15	-0.32	6	21
IBTK	0.028	0.007	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.027	0.16	0.39	1	-0.48	4	5
PTPN6	-0.058	0.15	-10000	0	-0.48	26	26
RELA	0.03	0.003	-10000	0	-10000	0	0
BCL2A1	0.004	0.06	0.15	12	-0.13	3	15
VAV2	-0.074	0.19	-10000	0	-0.51	62	62
ubiquitin-dependent protein catabolic process	0.025	0.052	0.14	30	-0.13	4	34
BTK	-0.041	0.15	-10000	0	-0.88	11	11
CD19	-0.091	0.21	-10000	0	-0.57	67	67
MAP4K1	-0.22	0.3	-10000	0	-0.59	214	214
CD72	-0.12	0.26	-10000	0	-0.59	124	124
PAG1	0.028	0.007	-10000	0	-10000	0	0
MAPK14	-0.033	0.18	0.37	21	-0.42	19	40
SH3BP5	0.02	0.032	-10000	0	-0.64	1	1
PIK3AP1	0.001	0.095	0.3	1	-0.45	3	4
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.061	0.14	-10000	0	-0.46	12	12
RAF1	0.001	0.091	0.31	3	-10000	0	3
RasGAP/p62DOK/SHIP	-0.077	0.23	-10000	0	-0.61	46	46
CD79A	-0.12	0.27	-10000	0	-0.59	128	128
re-entry into mitotic cell cycle	0.013	0.11	0.29	23	-0.28	6	29
RASA1	0.025	0.03	-10000	0	-0.64	1	1
MAPK3	0.018	0.1	0.39	9	-10000	0	9
MAPK1	0.014	0.093	0.38	5	-10000	0	5
CD72/SHP1	-0.11	0.23	0.34	1	-0.54	85	86
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MAPK8	-0.035	0.18	0.37	22	-0.42	18	40
actin cytoskeleton organization	-0.048	0.18	0.36	5	-0.48	37	42
NF-kappa-B/RelA	0.057	0.088	0.27	26	-10000	0	26
Calcineurin	0.02	0.089	-10000	0	-10000	0	0
PI3K	-0.074	0.16	-10000	0	-0.49	37	37
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.007	0.091	0.31	1	-0.38	6	7
SOS1	0.029	0.005	-10000	0	-10000	0	0
Bam32/HPK1	-0.14	0.23	-10000	0	-0.58	43	43
DAPP1	-0.041	0.15	-10000	0	-0.69	11	11
cytokine secretion	-0.035	0.14	0.37	7	-0.37	28	35
mol:DAG	-0.007	0.094	-10000	0	-0.33	7	7
PLCG2	0.02	0.073	-10000	0	-0.61	7	7
MAP2K1	0.01	0.094	0.37	4	-10000	0	4
B-cell antigen/BCR complex/FcgammaRIIB	-0.11	0.26	-10000	0	-0.46	166	166
mol:PI-3-4-5-P3	-0.057	0.12	-10000	0	-0.37	20	20
ETS1	0.007	0.088	0.43	2	-10000	0	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.021	0.17	-10000	0	-0.62	3	3
B-cell antigen/BCR complex/LYN	-0.062	0.14	-10000	0	-0.4	34	34
MALT1	0.029	0.005	-10000	0	-10000	0	0
TRAF6	0.03	0.003	-10000	0	-10000	0	0
RAC1	-0.054	0.19	0.33	2	-0.51	37	39
B-cell antigen/BCR complex/LYN/SYK	-0.057	0.18	-10000	0	-0.53	27	27
CARD11	-0.042	0.18	0.36	8	-0.42	54	62
FCGR2B	-0.078	0.23	-10000	0	-0.59	90	90
PPP3CA	0.03	0.003	-10000	0	-10000	0	0
BCL10	0.029	0.006	-10000	0	-10000	0	0
IKK complex	0.02	0.071	0.2	35	-10000	0	35
PTPRC	-0.034	0.19	-10000	0	-0.59	53	53
PDPK1	-0.021	0.11	0.36	8	-0.29	7	15
PPP3CB	0.029	0.006	-10000	0	-10000	0	0
PPP3CC	0.027	0.009	-10000	0	-10000	0	0
POU2F2	0.012	0.054	0.15	12	-0.12	1	13

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.064	0.15	-10000	0	-0.53	17	17
UGCG	-0.012	0.11	-10000	0	-0.57	19	19
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.035	0.15	0.35	3	-0.43	23	26
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.011	0.11	-10000	0	-0.56	19	19
mol:DAG	-0.013	0.13	-10000	0	-0.84	12	12
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.14	0.29	1	-0.44	17	18
FRAP1	-0.038	0.16	0.36	3	-0.48	24	27
FOXO3	-0.034	0.16	0.36	4	-0.46	22	26
AKT1	-0.043	0.16	0.31	1	-0.48	28	29
GAB2	0.03	0.003	-10000	0	-10000	0	0
SMPD1	0.007	0.046	-10000	0	-0.74	1	1
SGMS1	-0.007	0.11	-10000	0	-0.7	12	12
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	0.013	0.027	-10000	0	-0.4	2	2
CALM1	0.028	0.008	-10000	0	-10000	0	0
cell proliferation	-0.014	0.12	0.3	4	-0.5	16	20
EIF3A	0.029	0.006	-10000	0	-10000	0	0
PI3K	0.041	0.036	-10000	0	-0.47	2	2
RPS6KB1	-0.017	0.12	-10000	0	-0.91	6	6
mol:sphingomyelin	-0.013	0.13	-10000	0	-0.84	12	12
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.092	0.25	-10000	0	-0.59	105	105
PIK3R1	0.028	0.03	-10000	0	-0.63	1	1
JAK1	0.031	0.007	-10000	0	-10000	0	0
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MYC	-0.031	0.16	0.43	4	-0.57	8	12
MYB	-0.097	0.21	-10000	0	-0.58	24	24
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.054	0.16	0.26	1	-0.5	36	37
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.009	0.12	-10000	0	-0.86	6	6
mol:PI-3-4-5-P3	-0.053	0.16	0.26	1	-0.48	36	37
Rac1/GDP	0.027	0.028	-10000	0	-0.36	2	2
T cell proliferation	-0.046	0.16	0.31	1	-0.46	33	34
SHC1	0.029	0.007	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.007	0.021	-10000	0	-0.041	137	137
PRKCZ	-0.046	0.16	-10000	0	-0.48	32	32
NF kappa B1 p50/RelA	-0.014	0.15	0.31	1	-0.45	15	16
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.081	0.16	-10000	0	-0.48	45	45
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
RELA	0.03	0.003	-10000	0	-10000	0	0
IL2RA	-0.09	0.24	-10000	0	-0.59	101	101
IL2RB	-0.29	0.31	-10000	0	-0.59	272	272
TERT	-0.05	0.2	-10000	0	-0.59	61	61
E2F1	-0.048	0.14	-10000	0	-0.41	26	26
SOS1	0.029	0.005	-10000	0	-10000	0	0
RPS6	0.026	0.039	-10000	0	-0.59	2	2
mol:cAMP	0.003	0.01	0.02	137	-10000	0	137
PTPN11	0.029	0.006	-10000	0	-10000	0	0
IL2RG	-0.008	0.15	-10000	0	-0.59	34	34
actin cytoskeleton organization	-0.046	0.16	0.31	1	-0.46	33	34
GRB2	0.03	0.005	-10000	0	-10000	0	0
IL2	0.015	0.085	-10000	0	-0.59	10	10
PIK3CA	0.029	0.03	-10000	0	-0.63	1	1
Rac1/GTP	0.047	0.037	-10000	0	-0.34	2	2
LCK	0.005	0.12	-10000	0	-0.59	22	22
BCL2	-0.021	0.14	0.45	2	-0.47	3	5

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.035	0.055	-10000	0	-0.44	5	5
VEGFR1 homodimer/NRP1	0.015	0.052	-10000	0	-0.43	7	7
mol:DAG	-0.17	0.18	-10000	0	-0.7	6	6
VEGFR1 homodimer/NRP1/VEGFR 121	-0.13	0.19	-10000	0	-0.58	7	7
CaM/Ca2+	-0.15	0.18	-10000	0	-0.66	6	6
HIF1A	0.03	0.049	-10000	0	-0.62	2	2
GAB1	0.03	0.004	-10000	0	-10000	0	0
AKT1	-0.12	0.16	-10000	0	-0.67	6	6
PLCG1	-0.17	0.19	-10000	0	-0.71	6	6
NOS3	-0.1	0.15	-10000	0	-0.54	10	10
CBL	0.028	0.029	-10000	0	-0.64	1	1
mol:NO	-0.096	0.15	0.72	1	-0.52	10	11
FLT1	0.022	0.061	-10000	0	-0.5	7	7
PGF	-0.32	0.31	-10000	0	-0.6	289	289
VEGFR1 homodimer/NRP2/VEGFR121	-0.12	0.2	-10000	0	-0.59	9	9
CALM1	0.028	0.008	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
eNOS/Hsp90	-0.083	0.16	0.56	1	-0.55	6	7
endothelial cell proliferation	-0.12	0.16	0.59	1	-0.57	8	9
mol:Ca2+	-0.17	0.18	-10000	0	-0.69	6	6
MAPK3	-0.15	0.16	0.46	2	-0.6	6	8
MAPK1	-0.15	0.16	0.46	2	-0.62	6	8
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
PLGF homodimer	-0.32	0.31	-10000	0	-0.59	289	289
PRKACA	0.03	0.002	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.009	0.14	-10000	0	-0.59	30	30
VEGFA homodimer	-0.25	0.31	-10000	0	-0.59	234	234
VEGFR1 homodimer/VEGFA homodimer	-0.14	0.21	-10000	0	-0.57	9	9
platelet activating factor biosynthetic process	-0.14	0.16	0.44	2	-0.58	6	8
PI3K	-0.14	0.19	-10000	0	-0.73	6	6
PRKCA	-0.16	0.17	0.58	1	-0.65	6	7
PRKCB	-0.16	0.17	0.58	1	-0.62	8	9
VEGFR1 homodimer/PLGF homodimer	-0.19	0.21	-10000	0	-0.55	18	18
VEGFA	-0.25	0.31	-10000	0	-0.59	234	234
VEGFB	0.03	0.003	-10000	0	-10000	0	0
mol:IP3	-0.17	0.18	-10000	0	-0.7	6	6
RASA1	0.022	0.055	-10000	0	-0.7	1	1
NRP2	0.02	0.071	-10000	0	-0.59	7	7
VEGFR1 homodimer	0.021	0.061	-10000	0	-0.5	7	7
VEGFB homodimer	0.03	0.003	-10000	0	-10000	0	0
NCK1	0.027	0.03	-10000	0	-0.64	1	1
eNOS/Caveolin-1	-0.1	0.16	-10000	0	-0.53	25	25
PTPN11	0.029	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.14	0.19	-10000	0	-0.72	6	6
mol:L-citrulline	-0.096	0.15	0.72	1	-0.52	10	11
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.1	0.2	-10000	0	-0.68	5	5
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.12	0.2	-10000	0	-0.66	6	6
CD2AP	0.029	0.006	-10000	0	-10000	0	0
PI3K/GAB1	-0.13	0.19	-10000	0	-0.69	6	6
PDPK1	-0.13	0.18	0.35	1	-0.7	6	7
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.12	0.2	-10000	0	-0.66	5	5
mol:NADP	-0.096	0.15	0.72	1	-0.52	10	11
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.1	0.19	-10000	0	-0.67	5	5
VEGFR1 homodimer/NRP2	0.03	0.069	-10000	0	-0.44	5	5

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.023	0.013	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.062	0.13	-10000	0	-0.44	25	25
PTP1B/AKT1	-0.051	0.072	-10000	0	-0.33	5	5
FYN	0.028	0.008	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.065	0.075	0.37	1	-0.31	10	11
EGFR	-0.011	0.066	-10000	0	-0.61	6	6
EGF/EGFR	-0.3	0.13	-10000	0	-0.36	393	393
CSF1	0.028	0.029	-10000	0	-0.64	1	1
AKT1	0.028	0.008	-10000	0	-10000	0	0
INSR	0.03	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.067	0.09	-10000	0	-0.4	16	16
Insulin Receptor/Insulin	-0.02	0.084	0.3	1	-10000	0	1
HCK	-0.003	0.14	-10000	0	-0.59	27	27
CRK	0.029	0.005	-10000	0	-10000	0	0
TYK2	-0.059	0.073	0.34	1	-0.35	5	6
EGF	-0.57	0.2	-10000	0	-0.63	474	474
YES1	0.029	0.005	-10000	0	-10000	0	0
CAV1	-0.14	0.11	0.32	5	-0.32	47	52
TXN	0.023	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.053	0.079	0.34	1	-0.4	6	7
cell migration	0.065	0.075	0.31	10	-0.37	1	11
STAT3	0.029	0.005	-10000	0	-10000	0	0
PRLR	-0.052	0.21	-10000	0	-0.64	62	62
ITGA2B	0.006	0.12	-10000	0	-0.59	19	19
CSF1R	0.017	0.061	-10000	0	-0.59	5	5
Prolactin Receptor/Prolactin	-0.029	0.16	-10000	0	-0.48	62	62
FGR	0.025	0.047	-10000	0	-0.59	3	3
PTP1B/p130 Cas	-0.058	0.072	-10000	0	-0.34	6	6
Crk/p130 Cas	-0.052	0.072	-10000	0	-0.36	3	3
DOK1	-0.026	0.081	0.3	4	-0.34	2	6
JAK2	-0.069	0.14	0.32	1	-0.42	42	43
Jak2/Leptin Receptor/Leptin	-0.04	0.12	-10000	0	-0.54	4	4
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
PTPN1	-0.066	0.076	0.37	1	-0.32	10	11
LYN	0.028	0.007	-10000	0	-10000	0	0
CDH2	0.01	0.11	-10000	0	-0.62	16	16
SRC	0.002	0.046	0.34	1	-0.52	2	3
ITGB3	0.022	0.065	-10000	0	-0.64	5	5
CAT1/PTP1B	-0.22	0.16	0.4	5	-0.45	74	79
CAPN1	0.028	0.003	-10000	0	-10000	0	0
CSK	0.03	0.003	-10000	0	-10000	0	0
PI3K	0.002	0.084	-10000	0	-0.56	1	1
mol:H2O2	-0.006	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.033	0.11	-10000	0	-0.53	4	4
negative regulation of transcription	-0.067	0.14	0.32	1	-0.42	42	43
FCGR2A	0.001	0.13	-10000	0	-0.59	23	23
FER	0.017	0.042	-10000	0	-0.65	2	2
alphaIIb/beta3 Integrin	0.019	0.1	-10000	0	-0.46	23	23
BLK	-0.013	0.15	-10000	0	-0.59	34	34
Insulin Receptor/Insulin/Shc	0.05	0.013	-10000	0	-10000	0	0
RHOA	0.02	0.013	-10000	0	-10000	0	0
LEPR	0.029	0.006	-10000	0	-10000	0	0
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
p210 bcr-abl/Grb2	0.029	0.005	-10000	0	-10000	0	0
mol:NADPH	-0.006	0.003	-10000	0	-10000	0	0
TRPV6	-0.19	0.16	0.36	4	-0.43	102	106
PRL	0.002	0.022	-10000	0	-10000	0	0
SOCS3	0.025	0.12	-10000	0	-0.98	6	6
SPRY2	0.025	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.046	0.043	-10000	0	-0.42	4	4
CSF1/CSF1R	-0.047	0.075	0.34	1	-0.4	6	7
Ras protein signal transduction	0.034	0.069	0.5	10	-10000	0	10
IRS1	0.023	0.058	-10000	0	-0.64	4	4
INS	0.006	0.019	-10000	0	-10000	0	0
LEP	-0.039	0.17	-10000	0	-0.59	47	47
STAT5B	-0.059	0.093	0.37	1	-0.35	22	23
STAT5A	-0.059	0.093	0.37	1	-0.35	22	23
GRB2	0.029	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.047	0.068	0.34	1	-0.37	3	4
CSN2	0.003	0.072	-10000	0	-0.62	1	1
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
LAT	-0.056	0.11	-10000	0	-0.48	8	8
YBX1	0.033	0.008	-10000	0	-10000	0	0
LCK	0.003	0.12	-10000	0	-0.59	22	22
SHC1	0.029	0.007	-10000	0	-10000	0	0
NOX4	0.021	0.053	-10000	0	-0.56	4	4

×

Glucocorticoid receptor regulatory network

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
PCK2	0.037	0.089	-10000	0	-1.2	1	1
SMARCC2	0.031	0.005	-10000	0	-10000	0	0
SMARCC1	0.023	0.014	-10000	0	-10000	0	0
TBX21	-0.18	0.27	0.57	1	-0.55	173	174
SUMO2	0.024	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.035	0.037	-10000	0	-0.8	1	1
FKBP4	0.029	0.006	-10000	0	-10000	0	0
FKBP5	0.02	0.072	-10000	0	-0.6	7	7
GR alpha/HSP90/FKBP51/HSP90	0.065	0.1	0.39	3	-0.43	2	5
PRL	-0.029	0.11	-10000	0	-0.62	5	5
cortisol/GR alpha (dimer)/TIF2	0.12	0.22	0.54	52	-0.43	2	54
RELA	0.01	0.081	-10000	0	-0.31	1	1
FGG	-0.047	0.29	0.54	9	-0.51	80	89
GR beta/TIF2	0.049	0.12	0.36	7	-0.42	8	15
IFNG	-0.29	0.29	-10000	0	-0.71	108	108
apoptosis	-0.079	0.21	-10000	0	-0.6	26	26
CREB1	-0.003	0.1	-10000	0	-0.35	41	41
histone acetylation	-0.002	0.1	0.31	3	-0.42	5	8
BGLAP	-0.02	0.098	-10000	0	-0.63	2	2
GR/PKAc	0.074	0.094	0.38	3	-0.37	1	4
NF kappa B1 p50/RelA	0.016	0.15	-10000	0	-0.5	16	16
SMARCD1	0.031	0.005	-10000	0	-10000	0	0
MDM2	0.04	0.08	0.28	10	-10000	0	10
GATA3	-0.29	0.33	-10000	0	-0.63	258	258
AKT1	0.021	0.008	-10000	0	-10000	0	0
CSF2	-0.023	0.11	-10000	0	-0.66	4	4
GSK3B	0.023	0.012	-10000	0	-10000	0	0
NR1I3	-0.044	0.22	-10000	0	-0.73	15	15
CSN2	0.064	0.16	0.42	12	-0.38	1	13
BRG1/BAF155/BAF170/BAF60A	0.06	0.04	-10000	0	-10000	0	0
NFATC1	0.031	0.007	-10000	0	-10000	0	0
POU2F1	0.032	0.008	-10000	0	-10000	0	0
CDKN1A	0.033	0.059	0.85	1	-10000	0	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.041	0.2	-10000	0	-0.59	59	59
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.032	0.15	0.37	2	-0.4	14	16
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.018	0.24	-10000	0	-0.77	14	14
JUN	-0.19	0.21	-10000	0	-0.57	77	77
IL4	-0.029	0.092	-10000	0	-0.53	1	1
CDK5R1	0.027	0.006	-10000	0	-10000	0	0
PRKACA	0.03	0.002	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.22	0.26	9	-0.52	95	104
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.075	0.1	0.4	2	-0.42	1	3
cortisol/GR alpha (monomer)	0.14	0.26	0.62	58	-0.48	1	59
NCOA2	0.015	0.091	-10000	0	-0.64	10	10
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.045	0.12	-10000	0	-0.69	12	12
AP-1/NFAT1-c-4	-0.26	0.27	-10000	0	-0.72	76	76
AFP	-0.34	0.53	-10000	0	-1.3	109	109
SUV420H1	0.03	0.003	-10000	0	-10000	0	0
IRF1	0.067	0.11	0.48	5	-10000	0	5
TP53	0.051	0.018	-10000	0	-10000	0	0
PPP5C	0.03	0.003	-10000	0	-10000	0	0
KRT17	-0.22	0.34	-10000	0	-1	59	59
KRT14	-0.12	0.2	-10000	0	-0.6	47	47
TBP	0.036	0.014	-10000	0	-10000	0	0
CREBBP	0.053	0.058	-10000	0	-10000	0	0
HDAC1	0.027	0.006	-10000	0	-10000	0	0
HDAC2	0.028	0.011	-10000	0	-10000	0	0
AP-1	-0.26	0.27	-10000	0	-0.72	78	78
MAPK14	0.025	0.01	-10000	0	-10000	0	0
MAPK10	0.019	0.066	-10000	0	-0.64	5	5
MAPK11	0.022	0.04	-10000	0	-0.6	2	2
KRT5	-0.21	0.27	-10000	0	-0.71	76	76
interleukin-1 receptor activity	0	0.008	-10000	0	-10000	0	0
NCOA1	0.032	0.007	-10000	0	-10000	0	0
STAT1	0.035	0.038	-10000	0	-0.8	1	1
CGA	-0.13	0.33	-10000	0	-1.1	50	50
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.079	0.12	0.47	12	-10000	0	12
MAPK3	0.025	0.01	-10000	0	-10000	0	0
MAPK1	0.026	0.009	-10000	0	-10000	0	0
ICAM1	-0.054	0.18	-10000	0	-0.64	25	25
NFKB1	0.009	0.088	-10000	0	-0.8	1	1
MAPK8	-0.12	0.16	-10000	0	-0.47	37	37
MAPK9	0.02	0.013	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.084	0.22	-10000	0	-0.63	26	26
BAX	0.036	0.033	-10000	0	-10000	0	0
POMC	-0.051	0.14	0.49	1	-0.76	6	7
EP300	0.055	0.064	-10000	0	-0.53	1	1
cortisol/GR alpha (dimer)/p53	0.15	0.22	0.56	56	-10000	0	56
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.062	0.24	3	-10000	0	3
SGK1	0.075	0.089	-10000	0	-10000	0	0
IL13	-0.29	0.25	-10000	0	-0.71	84	84
IL6	-0.11	0.3	-10000	0	-0.86	58	58
PRKACG	0.02	0.006	-10000	0	-10000	0	0
IL5	-0.24	0.2	-10000	0	-0.65	37	37
IL2	-0.16	0.21	-10000	0	-0.7	25	25
CDK5	0.025	0.009	-10000	0	-10000	0	0
PRKACB	0.029	0.006	-10000	0	-10000	0	0
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
IL8	-0.075	0.24	-10000	0	-0.74	42	42
CDK5R1/CDK5	0.035	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.05	0.13	-10000	0	-0.54	2	2
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.21	0.54	48	-10000	0	48
SMARCA4	0.032	0.003	-10000	0	-10000	0	0
chromatin remodeling	0.07	0.12	0.39	18	-10000	0	18
NF kappa B1 p50/RelA/Cbp	0.073	0.14	-10000	0	-0.67	2	2
JUN (dimer)	-0.19	0.21	-10000	0	-0.57	77	77
YWHAH	0.03	0.004	-10000	0	-10000	0	0
VIPR1	-0.052	0.16	-10000	0	-0.77	15	15
NR3C1	0.065	0.15	0.46	20	-0.62	1	21
NR4A1	0.018	0.11	-10000	0	-0.62	15	15
TIF2/SUV420H1	0.032	0.071	-10000	0	-0.47	10	10
MAPKKK cascade	-0.079	0.21	-10000	0	-0.6	26	26
cortisol/GR alpha (dimer)/Src-1	0.14	0.22	0.56	51	-0.51	1	52
PBX1	0.011	0.12	-10000	0	-0.63	16	16
POU1F1	0.021	0.011	-10000	0	-10000	0	0
SELE	-0.096	0.32	-10000	0	-1.2	36	36
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.07	0.12	0.4	18	-10000	0	18
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.21	0.54	48	-10000	0	48
mol:cortisol	0.047	0.17	0.34	55	-0.29	26	81
MMP1	-0.17	0.32	-10000	0	-0.79	86	86

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.039	0.15	-9999	-0.43	44	44
FZD6	0.028	0.007	-9999	-10000	0	0
WNT6	0.005	0.12	-9999	-0.6	20	20
WNT4	-0.042	0.2	-9999	-0.62	57	57
FZD3	0.027	0.009	-9999	-10000	0	0
WNT5A	0.019	0.038	-9999	-0.43	3	3
WNT11	-0.018	0.17	-9999	-0.63	38	38

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.018	0.038	-10000	0	-0.47	3	3
MAP4K4	0.013	0.066	-10000	0	-0.5	2	2
BAG4	0.026	0.03	-10000	0	-0.64	1	1
PKC zeta/ceramide	-0.1	0.084	-10000	0	-0.31	52	52
NFKBIA	0.028	0.007	-10000	0	-10000	0	0
BIRC3	-0.064	0.22	-10000	0	-0.59	79	79
BAX	-0.036	0.036	-10000	0	-0.3	4	4
RIPK1	0.029	0.006	-10000	0	-10000	0	0
AKT1	0.028	0.068	0.89	3	-10000	0	3
BAD	-0.1	0.079	-10000	0	-0.3	49	49
SMPD1	0.022	0.054	0.28	9	-10000	0	9
RB1	-0.1	0.078	-10000	0	-0.3	48	48
FADD/Caspase 8	0.023	0.077	-10000	0	-0.48	3	3
MAP2K4	-0.08	0.076	-10000	0	-0.43	5	5
NSMAF	0.028	0.007	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.077	0.087	-10000	0	-0.32	29	29
EGF	-0.57	0.2	-10000	0	-0.63	474	474
mol:ceramide	-0.11	0.083	0.18	1	-0.3	57	58
MADD	0.03	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.018	0.023	-10000	0	-0.47	1	1
ASAH1	0.027	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.1	0.077	-10000	0	-0.3	48	48
cell proliferation	-0.058	0.073	-10000	0	-0.4	8	8
BID	-0.004	0.071	-10000	0	-0.54	4	4
MAP3K1	-0.092	0.073	-10000	0	-0.29	38	38
EIF2A	-0.076	0.083	0.3	5	-0.6	3	8
TRADD	0.029	0.006	-10000	0	-10000	0	0
CRADD	0.029	0.005	-10000	0	-10000	0	0
MAPK3	-0.077	0.073	-10000	0	-0.46	7	7
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.077	0.073	-10000	0	-0.46	7	7
Cathepsin D/ceramide	-0.1	0.08	-10000	0	-0.3	49	49
FADD	0.014	0.066	-10000	0	-0.5	2	2
KSR1	-0.1	0.083	0.19	1	-0.31	52	53
MAPK8	-0.082	0.086	-10000	0	-0.41	15	15
PRKRA	-0.099	0.08	-10000	0	-0.3	47	47
PDGFA	0.025	0.03	-10000	0	-0.64	1	1
TRAF2	0.029	0.005	-10000	0	-10000	0	0
IGF1	0.023	0.06	-10000	0	-0.59	5	5
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.083	0.18	1	-0.3	57	58
CTSD	0.029	0.029	-10000	0	-0.64	1	1
regulation of nitric oxide biosynthetic process	0.043	0.023	-10000	0	-0.47	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.061	0.079	-10000	0	-0.44	8	8
PRKCD	0.02	0.03	-10000	0	-0.59	1	1
PRKCZ	0.025	0.05	-10000	0	-0.64	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.018	0.023	-10000	0	-0.47	1	1
RelA/NF kappa B1	0.043	0.023	-10000	0	-0.47	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.028	0.029	-10000	0	-0.64	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.014	0.071	-10000	0	-0.53	2	2
TNFR1A/BAG4/TNF-alpha	0.045	0.061	-10000	0	-0.39	9	9
mol:Sphingosine-1-phosphate	0.018	0.038	-10000	0	-0.47	3	3
MAP2K1	-0.083	0.076	-10000	0	-0.48	7	7
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.03	0.003	-10000	0	-10000	0	0
CYCS	-0.055	0.035	-10000	0	-0.31	4	4
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
TNFR1A/BAG4	0.039	0.026	-10000	0	-0.47	1	1
EIF2AK2	-0.087	0.088	0.27	6	-0.29	39	45
TNF-alpha/TNFR1A/FAN	0.047	0.057	-10000	0	-0.39	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.072	-10000	0	-0.42	6	6
MAP2K2	-0.084	0.074	-10000	0	-0.46	7	7
SMPD3	0.017	0.054	0.21	2	-0.41	2	4
TNF	0.019	0.079	-10000	0	-0.61	8	8
PKC zeta/PAR4	0.037	0.046	-10000	0	-0.47	4	4
mol:PHOSPHOCHOLINE	0.21	0.087	0.24	423	-10000	0	423
NF kappa B1/RelA/I kappa B alpha	0.075	0.046	-10000	0	-10000	0	0
AIFM1	-0.062	0.049	-10000	0	-0.35	4	4
BCL2	0.029	0.005	-10000	0	-10000	0	0

×

Regulation of Telomerase

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.17	0.21	0.49	1	-0.67	47	48
RAD9A	0.03	0.003	-10000	0	-10000	0	0
AP1	0.027	0.077	-10000	0	-0.47	12	12
IFNAR2	0.028	0.009	-10000	0	-10000	0	0
AKT1	0.013	0.051	-10000	0	-0.53	1	1
ER alpha/Oestrogen	0.016	0.044	-10000	0	-0.42	5	5
NFX1/SIN3/HDAC complex	0.029	0.068	-10000	0	-0.38	6	6
EGF	-0.57	0.2	-10000	0	-0.63	474	474
SMG5	0.029	0.007	-10000	0	-10000	0	0
SMG6	0.029	0.005	-10000	0	-10000	0	0
SP3/HDAC2	0.038	0.018	-10000	0	-10000	0	0
TERT/c-Abl	-0.16	0.2	-10000	0	-0.64	44	44
SAP18	0.029	0.005	-10000	0	-10000	0	0
MRN complex	0.044	0.027	-10000	0	-10000	0	0
WT1	-0.28	0.33	-10000	0	-0.64	241	241
WRN	0.027	0.009	-10000	0	-10000	0	0
SP1	0.026	0.014	-10000	0	-10000	0	0
SP3	0.028	0.007	-10000	0	-10000	0	0
TERF2IP	0.029	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.14	0.19	-10000	0	-0.62	28	28
Mad/Max	0.039	0.015	-10000	0	-10000	0	0
TERT	-0.18	0.22	0.5	1	-0.7	45	46
CCND1	-0.16	0.21	0.65	1	-0.7	30	31
MAX	0.027	0.008	-10000	0	-10000	0	0
RBBP7	0.029	0.003	-10000	0	-10000	0	0
RBBP4	0.027	0.03	-10000	0	-0.64	1	1
TERF2	0.026	0.007	-10000	0	-10000	0	0
PTGES3	0.029	0.005	-10000	0	-10000	0	0
SIN3A	0.03	0.003	-10000	0	-10000	0	0
Telomerase/911	0.028	0.043	-10000	0	-10000	0	0
CDKN1B	-0.12	0.18	-10000	0	-0.67	1	1
RAD1	0.027	0.009	-10000	0	-10000	0	0
XRCC5	0.028	0.007	-10000	0	-10000	0	0
XRCC6	0.03	0.004	-10000	0	-10000	0	0
SAP30	0.008	0.11	-10000	0	-0.59	18	18
TRF2/PARP2	0.039	0.013	-10000	0	-10000	0	0
UBE3A	0.029	0.004	-10000	0	-10000	0	0
JUN	0.028	0.007	-10000	0	-10000	0	0
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.02	0.009	-10000	0	-10000	0	0
FOS	0.012	0.099	-10000	0	-0.63	12	12
IFN-gamma/IRF1	-0.15	0.22	-10000	0	-0.42	190	190
PARP2	0.028	0.007	-10000	0	-10000	0	0
BLM	0.017	0.089	-10000	0	-0.59	11	11
Telomerase	-0.021	0.12	-10000	0	-0.63	3	3
IRF1	0.025	0.03	-10000	0	-0.58	1	1
ESR1	0.022	0.059	-10000	0	-0.56	5	5
KU/TER	0.042	0.011	-10000	0	-10000	0	0
ATM/TRF2	0.042	0.023	-10000	0	-0.42	1	1
ubiquitin-dependent protein catabolic process	0.04	0.056	-10000	0	-0.39	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.04	0.057	-10000	0	-0.4	2	2
HDAC1	0.029	0.006	-10000	0	-10000	0	0
HDAC2	0.025	0.014	-10000	0	-10000	0	0
ATM	0.01	0.022	-10000	0	-0.46	1	1
SMAD3	0.02	0.04	-10000	0	-0.43	4	4
ABL1	0.029	0.005	-10000	0	-10000	0	0
MXD1	0.029	0.006	-10000	0	-10000	0	0
MRE11A	0.03	0.004	-10000	0	-10000	0	0
HUS1	0.027	0.009	-10000	0	-10000	0	0
RPS6KB1	0.029	0.005	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.12	0.2	-10000	0	-0.69	24	24
NR2F2	0.031	0.007	-10000	0	-10000	0	0
MAPK3	0.007	0.063	-10000	0	-0.44	10	10
MAPK1	0.007	0.063	-10000	0	-0.44	10	10
TGFB1/TGF beta receptor Type II	0.025	0.054	-10000	0	-0.59	4	4
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
HNRNPC	0.028	0.007	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.01	0.022	-10000	0	-0.46	1	1
NBN	0.028	0.007	-10000	0	-10000	0	0
EGFR	0.02	0.067	-10000	0	-0.6	6	6
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.41	0.16	-10000	0	-0.48	425	425
MYC	0.006	0.12	-10000	0	-0.59	19	19
IL2	0.008	0.086	-10000	0	-0.59	10	10
KU	0.042	0.011	-10000	0	-10000	0	0
RAD50	0.023	0.013	-10000	0	-10000	0	0
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
TGFB1	0.025	0.054	-10000	0	-0.59	4	4
TRF2/BLM	0.032	0.065	-10000	0	-0.41	11	11
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.15	0.2	-10000	0	-0.66	38	38
SP1/HDAC2	0.035	0.025	-10000	0	-10000	0	0
PINX1	0.027	0.009	-10000	0	-10000	0	0
Telomerase/EST1A	-0.14	0.19	-10000	0	-0.62	30	30
Smad3/Myc	0.02	0.086	-10000	0	-0.38	22	22
911 complex	0.051	0.023	-10000	0	-10000	0	0
IFNG	-0.24	0.3	-10000	0	-0.58	232	232
Telomerase/PinX1	-0.14	0.19	-10000	0	-0.62	30	30
Telomerase/AKT1/mTOR/p70S6K	-0.019	0.096	-10000	0	-0.48	4	4
SIN3B	0.03	0.003	-10000	0	-10000	0	0
YWHAE	0.029	0.005	-10000	0	-10000	0	0
Telomerase/EST1B	-0.14	0.19	-10000	0	-0.61	30	30
response to DNA damage stimulus	0.006	0.012	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.062	0.039	-10000	0	-10000	0	0
TRF2/WRN	0.038	0.015	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.19	-10000	0	-0.62	28	28
E2F1	-0.036	0.19	-10000	0	-0.59	54	54
ZNFX1	0.029	0.006	-10000	0	-10000	0	0
PIF1	-0.08	0.24	-10000	0	-0.59	93	93
NCL	0.028	0.007	-10000	0	-10000	0	0
DKC1	0.03	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.07	0.26	-10000	0	-0.89	29	29
NCK1/PAK1/Dok-R	-0.063	0.1	-10000	0	-0.41	27	27
NCK1/Dok-R	0.006	0.27	-10000	0	-1	30	30
PIK3CA	0.026	0.03	-10000	0	-0.63	1	1
mol:beta2-estradiol	-0.003	0.035	0.27	8	-10000	0	8
RELA	0.03	0.003	-10000	0	-10000	0	0
SHC1	0.028	0.007	-10000	0	-10000	0	0
Rac/GDP	0.02	0.007	-10000	0	-10000	0	0
F2	-0.2	0.3	0.27	3	-0.58	195	198
TNIP2	0.03	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	0.046	0.26	-10000	0	-0.95	30	30
FN1	-0.017	0.16	-10000	0	-0.6	38	38
PLD2	0.004	0.28	-10000	0	-1.1	30	30
PTPN11	0.029	0.005	-10000	0	-10000	0	0
GRB14	-0.005	0.15	-10000	0	-0.64	27	27
ELK1	0.02	0.25	-10000	0	-0.93	30	30
GRB7	0.02	0.076	-10000	0	-0.64	7	7
PAK1	0.03	0.003	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.002	0.29	-10000	0	-1	29	29
CDKN1A	-0.077	0.24	-10000	0	-0.63	25	25
ITGA5	-0.012	0.15	-10000	0	-0.59	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.001	0.27	-10000	0	-1	30	30
CRK	0.029	0.005	-10000	0	-10000	0	0
mol:NO	-0.028	0.22	0.44	5	-0.63	29	34
PLG	-0.16	0.31	-10000	0	-1.2	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.045	0.23	-10000	0	-0.82	29	29
GRB2	0.029	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.03	-10000	0	-0.64	1	1
ANGPT2	-0.13	0.27	-10000	0	-0.65	31	31
BMX	-0.042	0.29	-10000	0	-1.1	30	30
ANGPT1	0.045	0.17	-10000	0	-1.2	8	8
tube development	-0.096	0.25	-10000	0	-0.7	28	28
ANGPT4	0.003	0.11	-10000	0	-0.6	16	16
response to hypoxia	-0.005	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.004	0.3	-10000	0	-1.1	30	30
alpha5/beta1 Integrin	0.011	0.12	-10000	0	-0.43	35	35
FGF2	0.028	0.065	-10000	0	-0.62	5	5
STAT5A (dimer)	-0.097	0.28	-10000	0	-0.79	28	28
mol:L-citrulline	-0.028	0.22	0.44	5	-0.63	29	34
AGTR1	-0.023	0.14	-10000	0	-0.63	25	25
MAPK14	-0.029	0.3	-10000	0	-1.1	32	32
Tie2/SHP2	-0.002	0.26	-10000	0	-1.1	28	28
TEK	-0.007	0.29	-10000	0	-1.2	28	28
RPS6KB1	-0.042	0.25	-10000	0	-0.83	30	30
Angiotensin II/AT1	-0.026	0.1	-10000	0	-0.47	25	25
Tie2/Ang1/GRB2	0.015	0.29	-10000	0	-1.1	30	30
MAPK3	0.01	0.25	-10000	0	-0.95	30	30
MAPK1	0.008	0.25	-10000	0	-0.96	30	30
Tie2/Ang1/GRB7	0.011	0.29	-10000	0	-1.1	30	30
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MAPK8	0.002	0.28	-10000	0	-1.1	30	30
PI3K	-0.061	0.28	-10000	0	-1	30	30
FES	-0.024	0.29	-10000	0	-1.1	31	31
Crk/Dok-R	0.009	0.28	-10000	0	-1	29	29
Tie2/Ang1/ABIN2	0.014	0.29	-10000	0	-1.1	30	30
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.059	0.24	0.44	1	-0.78	30	31
STAT5A	0.03	0.005	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.039	0.25	0.51	1	-0.84	29	30
Tie2/Ang2	-0.13	0.31	-10000	0	-0.98	28	28
Tie2/Ang1	0.001	0.3	-10000	0	-1.2	30	30
FOXO1	-0.079	0.25	-10000	0	-0.8	28	28
ELF1	0.031	0.042	-10000	0	-0.63	1	1
ELF2	0.003	0.28	-10000	0	-1.1	30	30
mol:Choline	0.007	0.26	-10000	0	-1	30	30
cell migration	-0.043	0.064	-10000	0	-0.25	9	9
FYN	-0.11	0.27	-10000	0	-0.81	28	28
DOK2	-0.01	0.15	-10000	0	-0.59	31	31
negative regulation of cell cycle	-0.068	0.22	-10000	0	-0.56	30	30
ETS1	0.035	0.04	-10000	0	-0.29	5	5
PXN	-0.022	0.22	0.5	7	-0.69	28	35
ITGB1	0.029	0.004	-10000	0	-10000	0	0
NOS3	-0.038	0.23	0.52	2	-0.72	29	31
RAC1	0.027	0.009	-10000	0	-10000	0	0
TNF	0.02	0.088	-10000	0	-0.58	9	9
MAPKKK cascade	0.007	0.26	-10000	0	-1	30	30
RASA1	0.025	0.03	-10000	0	-0.64	1	1
Tie2/Ang1/Shc	0.007	0.28	-10000	0	-1.1	30	30
NCK1	0.027	0.03	-10000	0	-0.64	1	1
vasculogenesis	-0.022	0.2	0.41	8	-0.56	29	37
mol:Phosphatidic acid	0.007	0.26	-10000	0	-1	30	30
mol:Angiotensin II	-0.011	0.015	-10000	0	-10000	0	0
mol:NADP	-0.028	0.22	0.44	5	-0.63	29	34
Rac1/GTP	-0.041	0.22	-10000	0	-0.78	29	29
MMP2	-0.001	0.28	-10000	0	-1.1	30	30

×

FoxO family signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.56	0.64	-10000	0	-1.2	245	245
PLK1	-0.13	0.24	0.48	1	-0.7	24	25
CDKN1B	-0.01	0.15	0.54	1	-0.38	1	2
FOXO3	-0.068	0.18	-10000	0	-0.59	17	17
KAT2B	0.013	0.039	-10000	0	-0.67	1	1
FOXO1/SIRT1	-0.13	0.22	-10000	0	-0.38	215	215
CAT	-0.082	0.19	0.48	1	-1	4	5
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
AKT1	-0.01	0.05	-10000	0	-10000	0	0
FOXO1	-0.17	0.23	0.3	1	-0.42	226	227
MAPK10	0.037	0.069	0.34	3	-0.36	4	7
mol:GTP	0.002	0.001	-10000	0	-10000	0	0
FOXO4	0.094	0.086	0.38	14	-10000	0	14
response to oxidative stress	-0.028	0.042	-10000	0	-0.29	1	1
FOXO3A/SIRT1	-0.022	0.19	-10000	0	-0.59	12	12
XPO1	0.03	0.005	-10000	0	-10000	0	0
EP300	-0.011	0.055	-10000	0	-0.48	2	2
BCL2L11	0.005	0.084	-10000	0	-0.72	6	6
FOXO1/SKP2	-0.14	0.21	-10000	0	-0.39	196	196
mol:GDP	-0.028	0.042	-10000	0	-0.29	1	1
RAN	0.031	0.006	-10000	0	-10000	0	0
GADD45A	0.059	0.16	-10000	0	-0.63	14	14
YWHAQ	0.029	0.005	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.031	0.11	-10000	0	-0.55	8	8
MST1	0.004	0.082	-10000	0	-0.62	8	8
CSNK1D	0.029	0.005	-10000	0	-10000	0	0
CSNK1E	0.03	0.004	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.027	0.11	-10000	0	-0.61	7	7
YWHAB	0.029	0.006	-10000	0	-10000	0	0
MAPK8	0.039	0.063	0.34	2	-0.37	2	4
MAPK9	0.025	0.048	0.35	2	-10000	0	2
YWHAG	0.027	0.009	-10000	0	-10000	0	0
YWHAE	0.029	0.005	-10000	0	-10000	0	0
YWHAZ	0.028	0.007	-10000	0	-10000	0	0
SIRT1	0.044	0.018	-10000	0	-10000	0	0
SOD2	-0.05	0.18	0.47	1	-0.54	14	15
RBL2	-0.021	0.16	-10000	0	-0.91	7	7
RAL/GDP	0.018	0.034	-10000	0	-10000	0	0
CHUK	0.021	0.026	-10000	0	-10000	0	0
Ran/GTP	0.026	0.005	-10000	0	-10000	0	0
CSNK1G2	0.028	0.029	-10000	0	-0.64	1	1
RAL/GTP	0.028	0.032	-10000	0	-10000	0	0
CSNK1G1	0.03	0.003	-10000	0	-10000	0	0
FASLG	-0.22	0.24	-10000	0	-0.67	9	9
SKP2	0.027	0.009	-10000	0	-10000	0	0
USP7	0.03	0.007	-10000	0	-10000	0	0
IKBKB	0.02	0.026	-10000	0	-10000	0	0
CCNB1	-0.069	0.19	-10000	0	-0.73	10	10
FOXO1-3a-4/beta catenin	-0.039	0.14	0.4	4	-0.43	1	5
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-10000	0	-0.38	196	196
CSNK1A1	0.023	0.013	-10000	0	-10000	0	0
SGK1	0.02	0.026	-10000	0	-10000	0	0
CSNK1G3	0.023	0.012	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.045	0.012	-10000	0	-10000	0	0
ZFAND5	0.095	0.085	0.45	9	-10000	0	9
SFN	-0.041	0.2	-10000	0	-0.59	59	59
CDK2	-0.02	0.059	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.007	0.11	-10000	0	-0.53	12	12
CREBBP	-0.018	0.057	-10000	0	-10000	0	0
FBXO32	-0.076	0.18	0.48	1	-0.69	6	7
BCL6	-0.026	0.17	-10000	0	-0.8	8	8
RALB	0.031	0.005	-10000	0	-10000	0	0
RALA	0.028	0.01	-10000	0	-10000	0	0
YWHAH	0.03	0.004	-10000	0	-10000	0	0

×

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

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
BAG4	0.026	0.03	-10000	0	-0.64	1	1
Caspase 8 (4 units)	-0.062	0.11	-10000	0	-0.38	1	1
NEF	-0.056	0.076	-10000	0	-0.46	5	5
NFKBIA	0.013	0.046	-10000	0	-10000	0	0
BIRC3	-0.05	0.21	-10000	0	-0.55	79	79
CYCS	-0.073	0.11	-10000	0	-0.4	2	2
RIPK1	0.029	0.006	-10000	0	-10000	0	0
CD247	-0.25	0.34	-10000	0	-0.73	169	169
MAP2K7	-0.044	0.14	0.38	2	-0.6	14	16
protein ubiquitination	0.032	0.099	0.4	8	-0.55	3	11
CRADD	0.029	0.005	-10000	0	-10000	0	0
DAXX	0.029	0.006	-10000	0	-10000	0	0
FAS	0.029	0.006	-10000	0	-10000	0	0
BID	-0.083	0.12	-10000	0	-0.36	2	2
NF-kappa-B/RelA/I kappa B alpha	0.014	0.12	-10000	0	-0.47	2	2
TRADD	0.029	0.006	-10000	0	-10000	0	0
MAP3K5	0.028	0.008	-10000	0	-10000	0	0
CFLAR	0.029	0.006	-10000	0	-10000	0	0
FADD	0.03	0.003	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.014	0.12	-10000	0	-0.47	2	2
MAPK8	-0.038	0.13	0.43	3	-0.59	11	14
APAF1	0.029	0.005	-10000	0	-10000	0	0
TRAF1	0.028	0.028	-10000	0	-0.59	1	1
TRAF2	0.029	0.005	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.09	0.12	-10000	0	-0.32	8	8
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.013	0.096	-10000	0	-0.65	4	4
CHUK	0.031	0.093	0.3	6	-0.62	3	9
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.078	0.03	-10000	0	-10000	0	0
TCRz/NEF	-0.26	0.31	-10000	0	-0.52	279	279
TNF	0.019	0.079	-10000	0	-0.61	8	8
FASLG	-0.36	0.4	-10000	0	-0.72	276	276
NFKB1	0.012	0.055	-10000	0	-0.63	1	1
TNFR1A/BAG4/TNF-alpha	0.045	0.061	-10000	0	-0.39	9	9
CASP6	-0.022	0.12	-10000	0	-0.56	11	11
CASP7	-0.065	0.16	0.38	1	-0.48	3	4
RELA	0.013	0.048	-10000	0	-10000	0	0
CASP2	0.027	0.009	-10000	0	-10000	0	0
CASP3	-0.062	0.16	0.38	1	-0.48	4	5
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.039	0.026	-10000	0	-0.47	1	1
CASP8	0.029	0.006	-10000	0	-10000	0	0
CASP9	0.029	0.006	-10000	0	-10000	0	0
MAP3K14	0.022	0.096	-10000	0	-0.72	3	3
APAF-1/Caspase 9	-0.088	0.16	-10000	0	-0.45	47	47
BCL2	-0.031	0.13	0.47	3	-0.55	10	13

×

Visual signal transduction: Rods

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
mol:K +	0.03	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.005	0.06	-10000	0	-0.47	8	8
Metarhodopsin II/Arrestin	0.016	0.069	-10000	0	-0.38	15	15
PDE6G/GNAT1/GTP	0.014	0.069	-10000	0	-0.4	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.006	0.081	-10000	0	-0.63	8	8
GRK1	0.02	0.006	-10000	0	-10000	0	0
CNG Channel	-0.046	0.16	-10000	0	-0.7	7	7
mol:Na +	-0.047	0.18	-10000	0	-0.56	21	21
mol:ADP	0.02	0.006	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.028	0.11	-10000	0	-0.39	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.041	0.19	-10000	0	-0.58	21	21
CNGB1	0.014	0.08	-10000	0	-0.59	9	9
RDH5	0.021	0.073	-10000	0	-0.6	7	7
SAG	0.017	0.027	-10000	0	-0.59	1	1
mol:Ca2+	-0.068	0.16	0.38	3	-0.56	19	22
Na + (4 Units)	-0.047	0.16	-10000	0	-0.54	19	19
RGS9	0.013	0.1	-10000	0	-0.58	14	14
GNB1/GNGT1	-0.1	0.21	-10000	0	-0.43	154	154
GNAT1/GDP	0.014	0.11	-10000	0	-0.36	34	34
GUCY2D	-0.004	0.13	-10000	0	-0.59	26	26
GNGT1	-0.16	0.28	-10000	0	-0.59	154	154
GUCY2F	0.019	0.004	-10000	0	-10000	0	0
GNB5	0.03	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.002	0.093	-10000	0	-0.48	10	10
mol:11-cis-retinal	0.021	0.073	-10000	0	-0.6	7	7
mol:cGMP	0.016	0.11	-10000	0	-0.38	14	14
GNB1	0.029	0.006	-10000	0	-10000	0	0
Rhodopsin	0.018	0.096	-10000	0	-0.44	22	22
SLC24A1	0.03	0.003	-10000	0	-10000	0	0
CNGA1	-0.093	0.26	-10000	0	-0.63	98	98
Metarhodopsin II	0.016	0.063	-10000	0	-0.35	15	15
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.025	0.11	-10000	0	-0.36	39	39
RGS9BP	0	0.14	-10000	0	-0.64	23	23
Metarhodopsin II/Transducin	-0.063	0.13	-10000	0	-0.37	50	50
GCAP Family/Ca ++	0.03	0.071	-10000	0	-0.37	15	15
PDE6A/B	0.016	0.092	-10000	0	-0.47	17	17
mol:Pi	0.027	0.11	-10000	0	-0.39	34	34
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.082	0.18	-10000	0	-0.34	157	157
PDE6B	0.023	0.065	-10000	0	-0.64	5	5
PDE6A	0.006	0.096	-10000	0	-0.59	13	13
PDE6G	0.023	0.064	-10000	0	-0.63	5	5
RHO	0.006	0.1	-10000	0	-0.59	15	15
PDE6	0.027	0.13	-10000	0	-0.64	5	5
GUCA1A	0.011	0.08	-10000	0	-0.59	9	9
GC2/GCAP Family	0.04	0.075	-10000	0	-0.37	15	15
GUCA1C	0.016	0.041	-10000	0	-0.64	2	2
GUCA1B	0.023	0.06	-10000	0	-0.59	5	5

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.11	0.18	-10000	0	-0.62	21	21
CRKL	0.006	0.11	-10000	0	-0.48	20	20
HRAS	-0.013	0.14	-10000	0	-0.53	10	10
mol:PIP3	0.011	0.12	-10000	0	-0.45	20	20
SPRED1	0.03	0.003	-10000	0	-10000	0	0
SPRED2	0.028	0.029	-10000	0	-0.64	1	1
GAB1	0.004	0.12	-10000	0	-0.49	24	24
FOXO3	0.012	0.14	0.46	1	-0.62	12	13
AKT1	0.009	0.16	-10000	0	-0.55	22	22
BAD	0.013	0.15	0.46	1	-0.63	12	13
megakaryocyte differentiation	-0.055	0.18	-10000	0	-0.46	57	57
GSK3B	0.015	0.15	0.42	1	-0.62	12	13
RAF1	-0.02	0.11	0.31	2	-0.43	8	10
SHC1	0.029	0.007	-10000	0	-10000	0	0
STAT3	0.003	0.12	-10000	0	-0.49	23	23
STAT1	-0.016	0.25	-10000	0	-1.1	24	24
HRAS/SPRED1	0.003	0.12	-10000	0	-0.42	10	10
cell proliferation	0.002	0.13	-10000	0	-0.5	25	25
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
TEC	0.029	0.004	-10000	0	-10000	0	0
RPS6KB1	0.01	0.14	-10000	0	-0.49	27	27
HRAS/SPRED2	0.002	0.12	-10000	0	-0.42	11	11
LYN/TEC/p62DOK	0.042	0.12	-10000	0	-0.52	12	12
MAPK3	0.012	0.099	0.31	9	-0.34	3	12
STAP1	-0.25	0.19	-10000	0	-0.41	157	157
GRAP2	-0.012	0.16	-10000	0	-0.59	35	35
JAK2	-0.016	0.23	-10000	0	-0.98	24	24
STAT1 (dimer)	-0.013	0.24	-10000	0	-1	24	24
mol:Gleevec	-0.002	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.038	0.18	-10000	0	-0.55	21	21
actin filament polymerization	-0.001	0.12	-10000	0	-0.5	21	21
LYN	0.028	0.007	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.22	0.21	-10000	0	-0.77	32	32
PIK3R1	0.026	0.03	-10000	0	-0.63	1	1
CBL/CRKL/GRB2	0.036	0.11	-10000	0	-0.54	7	7
PI3K	0.031	0.13	-10000	0	-0.51	18	18
PTEN	0.029	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.062	0.29	-10000	0	-1.2	24	24
MAPK8	0.001	0.13	-10000	0	-0.51	25	25
STAT3 (dimer)	0.003	0.12	-10000	0	-0.48	23	23
positive regulation of transcription	0.015	0.088	0.3	10	-0.27	3	13
mol:GDP	-0.03	0.16	-10000	0	-0.51	18	18
PIK3C2B	0.003	0.12	-10000	0	-0.48	24	24
CBL/CRKL	0.022	0.11	-10000	0	-0.46	17	17
FER	-0.003	0.12	-10000	0	-0.49	23	23
SH2B3	0.004	0.12	-10000	0	-0.49	23	23
PDPK1	0.02	0.12	0.34	6	-0.43	16	22
SNAI2	0.002	0.12	-10000	0	-0.5	23	23
positive regulation of cell proliferation	0.007	0.19	-10000	0	-0.79	24	24
KITLG	0.017	0.095	-10000	0	-0.65	10	10
cell motility	0.007	0.19	-10000	0	-0.79	24	24
PTPN6	0.027	0.008	-10000	0	-10000	0	0
EPOR	0.041	0.096	-10000	0	-1.1	2	2
STAT5A (dimer)	0.019	0.17	-10000	0	-0.62	27	27
SOCS1	0.022	0.066	-10000	0	-0.59	6	6
cell migration	0.028	0.16	0.51	30	-10000	0	30
SOS1	0.029	0.005	-10000	0	-10000	0	0
EPO	-0.17	0.28	-10000	0	-0.58	168	168
VAV1	-0.12	0.26	-10000	0	-0.59	123	123
GRB10	0.001	0.12	-10000	0	-0.49	22	22
PTPN11	0.028	0.007	-10000	0	-10000	0	0
SCF/KIT	0.003	0.13	-10000	0	-0.51	26	26
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.012	0.093	0.31	3	-0.39	3	6
CBL	0.028	0.029	-10000	0	-0.64	1	1
KIT	-0.01	0.29	-10000	0	-1.3	24	24
MAP2K2	-0.012	0.094	0.35	3	-0.39	3	6
SHC/Grb2/SOS1	0.043	0.12	-10000	0	-0.48	16	16
STAT5A	0.019	0.17	-10000	0	-0.65	27	27
GRB2	0.029	0.005	-10000	0	-10000	0	0
response to radiation	0.003	0.12	0.28	1	-0.49	23	24
SHC/GRAP2	0.01	0.12	-10000	0	-0.43	34	34
PTPRO	-0.057	0.18	-10000	0	-0.47	57	57
SH2B2	-0.002	0.12	-10000	0	-0.52	21	21
DOK1	0.029	0.005	-10000	0	-10000	0	0
MATK	-0.029	0.16	-10000	0	-0.53	30	30
CREBBP	0.046	0.032	-10000	0	-10000	0	0
BCL2	0.041	0.097	-10000	0	-0.88	2	2

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.023	0.063	-9999	-0.62	5	5
GNB1/GNG2	-0.025	0.15	-9999	-0.47	22	22
mol:DAG	-0.032	0.13	-9999	-0.44	19	19
PLCG1	-0.033	0.13	-9999	-0.46	19	19
YES1	-0.037	0.14	-9999	-0.41	42	42
FZD3	0.027	0.009	-9999	-10000	0	0
FZD6	0.028	0.007	-9999	-10000	0	0
G protein	-0.022	0.14	-9999	-0.46	19	19
MAP3K7	-0.089	0.17	-9999	-0.5	33	33
mol:Ca2+	-0.031	0.13	-9999	-0.43	19	19
mol:IP3	-0.032	0.13	-9999	-0.44	19	19
NLK	-0.001	0.089	-9999	-0.81	6	6
GNB1	0.029	0.006	-9999	-10000	0	0
CAMK2A	-0.098	0.18	-9999	-0.5	46	46
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.039	0.15	-9999	-0.43	44	44
CSNK1A1	0.023	0.013	-9999	-10000	0	0
GNAS	-0.037	0.14	-9999	-0.41	43	43
GO:0007205	-0.036	0.12	-9999	-0.43	21	21
WNT6	0.005	0.12	-9999	-0.6	20	20
WNT4	-0.042	0.2	-9999	-0.62	57	57
NFAT1/CK1 alpha	-0.015	0.13	-9999	-0.46	12	12
GNG2	0.028	0.008	-9999	-10000	0	0
WNT5A	0.019	0.038	-9999	-0.43	3	3
WNT11	-0.018	0.17	-9999	-0.63	38	38
CDC42	-0.033	0.13	-9999	-0.46	22	22

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.007	0.1	-10000	0	-0.37	34	34
EPHB2	0.019	0.076	-10000	0	-0.5	10	10
Syndecan-2/TACI	-0.005	0.12	-10000	0	-0.36	51	51
LAMA1	0.013	0.098	-10000	0	-0.56	14	14
Syndecan-2/alpha2 ITGB1	0.054	0.055	-10000	0	-0.34	1	1
HRAS	0.029	0.027	-10000	0	-0.59	1	1
Syndecan-2/CASK	0.015	0.004	-10000	0	-10000	0	0
ITGA5	-0.012	0.15	-10000	0	-0.59	35	35
BAX	0.021	0.024	-10000	0	-10000	0	0
EPB41	0.029	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.032	0.009	-10000	0	-10000	0	0
LAMA3	0.022	0.066	-10000	0	-0.59	6	6
EZR	0.028	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.02	0.067	-10000	0	-0.6	6	6
Syndecan-2/MMP2	0.03	0.042	-10000	0	-0.37	5	5
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.036	0.048	-10000	0	-0.47	4	4
dendrite morphogenesis	0.029	0.044	-10000	0	-0.4	4	4
Syndecan-2/GM-CSF	0.014	0.063	-10000	0	-0.36	13	13
determination of left/right symmetry	0.02	0.005	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.025	0.024	-10000	0	-0.36	1	1
GNB2L1	0.023	0.013	-10000	0	-10000	0	0
MAPK3	0.012	0.06	-10000	0	-0.33	13	13
MAPK1	0.013	0.061	-10000	0	-0.33	13	13
Syndecan-2/RACK1	0.037	0.028	-10000	0	-0.31	1	1
NF1	0.029	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.02	0.005	-10000	0	-10000	0	0
ITGA2	0.022	0.06	-10000	0	-0.57	5	5
MAPK8	0.023	0.027	-10000	0	-0.39	2	2
Syndecan-2/alpha2/beta1 Integrin	0.049	0.069	-10000	0	-10000	0	0
Syndecan-2/Kininogen	-0.28	0.19	-10000	0	-0.4	361	361
ITGB1	0.029	0.004	-10000	0	-10000	0	0
SRC	0.063	0.066	0.35	1	-10000	0	1
Syndecan-2/CASK/Protein 4.1	0.031	0.01	-10000	0	-10000	0	0
extracellular matrix organization	0.032	0.036	-10000	0	-0.36	4	4
actin cytoskeleton reorganization	0.007	0.1	-10000	0	-0.37	34	34
Syndecan-2/Caveolin-2/Ras	0.042	0.046	-10000	0	-0.36	1	1
Syndecan-2/Laminin alpha3	0.031	0.041	-10000	0	-0.36	5	5
Syndecan-2/RasGAP	0.046	0.042	-10000	0	-0.62	1	1
alpha5/beta1 Integrin	0.011	0.12	-10000	0	-0.43	35	35
PRKCD	0.02	0.03	-10000	0	-0.59	1	1
Syndecan-2 dimer	0.029	0.045	-10000	0	-0.4	4	4
GO:0007205	0.004	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.06	0.059	-10000	0	-0.6	1	1
RHOA	0.021	0.014	-10000	0	-10000	0	0
SDCBP	0.028	0.007	-10000	0	-10000	0	0
TNFRSF13B	-0.034	0.18	-10000	0	-0.59	52	52
RASA1	0.025	0.03	-10000	0	-0.64	1	1
alpha2/beta1 Integrin	0.036	0.048	-10000	0	-0.47	4	4
Syndecan-2/Synbindin	0.035	0.009	-10000	0	-10000	0	0
TGFB1	0.025	0.054	-10000	0	-0.59	4	4
CASP3	0.025	0.034	-10000	0	-0.33	1	1
FN1	-0.017	0.16	-10000	0	-0.6	38	38
Syndecan-2/IL8	0.009	0.099	-10000	0	-0.38	32	32
SDC2	0.02	0.005	-10000	0	-10000	0	0
KNG1	-0.45	0.29	-10000	0	-0.63	380	380
Syndecan-2/Neurofibromin	0.035	0.01	-10000	0	-10000	0	0
TRAPPC4	0.03	0.003	-10000	0	-10000	0	0
CSF2	0.002	0.099	-10000	0	-0.59	14	14
Syndecan-2/TGFB1	0.032	0.036	-10000	0	-0.36	4	4
Syndecan-2/Syntenin/PI-4-5-P2	0.032	0.009	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.037	0.026	-10000	0	-10000	0	0
PRKACA	0.034	0.03	-10000	0	-10000	0	0
angiogenesis	0.009	0.099	-10000	0	-0.37	32	32
MMP2	0.022	0.067	-10000	0	-0.6	6	6
IL8	-0.011	0.16	-10000	0	-0.6	34	34
calcineurin-NFAT signaling pathway	-0.005	0.12	-10000	0	-0.36	51	51

×

EPO signaling pathway

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
BCL2L1	0.02	0.11	0.46	3	-10000	0	3
CRKL	-0.031	0.16	0.38	14	-10000	0	14
mol:DAG	-0.025	0.12	-10000	0	-10000	0	0
HRAS	-0.009	0.16	0.44	14	-0.46	1	15
MAPK8	-0.061	0.17	0.36	1	-0.52	2	3
RAP1A	-0.032	0.16	0.38	15	-10000	0	15
GAB1	-0.032	0.16	0.36	13	-10000	0	13
MAPK14	-0.059	0.17	0.36	1	-10000	0	1
EPO	-0.17	0.29	-10000	0	-0.58	168	168
PLCG1	-0.025	0.12	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.016	0.032	-10000	0	-10000	0	0
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.076	0.19	-10000	0	-0.35	167	167
GAB1/SHC/GRB2/SOS1	-0.013	0.15	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.11	0.22	-10000	0	-0.43	168	168
IRS2	-0.037	0.16	0.37	13	-0.47	2	15
STAT1	-0.017	0.13	-10000	0	-10000	0	0
STAT5B	-0.022	0.12	-10000	0	-10000	0	0
cell proliferation	-0.054	0.17	0.38	6	-0.62	1	7
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.034	0.12	-10000	0	-0.47	1	1
TEC	-0.032	0.16	0.36	13	-10000	0	13
SOCS3	0.024	0.054	-10000	0	-0.59	4	4
STAT1 (dimer)	-0.016	0.12	-10000	0	-10000	0	0
JAK2	0.014	0.031	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
EPO/EPOR (dimer)/JAK2	-0.026	0.17	-10000	0	-10000	0	0
EPO/EPOR	-0.11	0.22	-10000	0	-0.43	168	168
LYN	0.03	0.008	-10000	0	-10000	0	0
TEC/VAV2	-0.026	0.15	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.016	0.032	-10000	0	-10000	0	0
SHC1	0.029	0.007	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.069	0.19	-10000	0	-0.34	157	157
mol:IP3	-0.025	0.12	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.022	0.15	0.41	2	-0.5	2	4
SH2B3	0.013	0.03	-10000	0	-10000	0	0
NFKB1	-0.059	0.17	0.36	1	-0.66	1	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.048	0.1	-10000	0	-0.34	7	7
PTPN6	-0.044	0.15	0.3	3	-10000	0	3
TEC/VAV2/GRB2	-0.017	0.15	-10000	0	-10000	0	0
EPOR	0.016	0.032	-10000	0	-10000	0	0
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
mol:GDP	-0.014	0.15	-10000	0	-10000	0	0
SOS1	0.029	0.005	-10000	0	-10000	0	0
PLCG2	0.02	0.073	-10000	0	-0.61	7	7
CRKL/CBL/C3G	-0.016	0.15	-10000	0	-0.54	1	1
VAV2	-0.031	0.16	0.37	14	-10000	0	14
CBL	-0.034	0.16	0.36	12	-0.58	1	13
SHC/Grb2/SOS1	-0.042	0.13	-10000	0	-10000	0	0
STAT5A	-0.022	0.12	-10000	0	-10000	0	0
GRB2	0.029	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	-0.005	0.13	-10000	0	-10000	0	0
LYN/PLCgamma2	0.036	0.055	-10000	0	-0.44	6	6
PTPN11	0.029	0.005	-10000	0	-10000	0	0
BTK	-0.097	0.2	0.38	13	-0.55	29	42
BCL2	0.022	0.12	0.42	4	-10000	0	4

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.03	0.004	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.025	0.052	-10000	0	-0.36	2	2
NT3 (dimer)/TRKC	0.013	0.12	-10000	0	-0.5	26	26
NT3 (dimer)/TRKB	-0.048	0.2	-10000	0	-0.42	106	106
SHC/Grb2/SOS1/GAB1/PI3K	0.036	0.031	-10000	0	-0.45	1	1
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0
BDNF	-0.052	0.21	-10000	0	-0.59	69	69
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
DYNLT1	0.028	0.008	-10000	0	-10000	0	0
NTRK1	-0.017	0.16	-10000	0	-0.61	37	37
NTRK2	-0.089	0.25	-10000	0	-0.62	96	96
NTRK3	-0.006	0.15	-10000	0	-0.64	28	28
NT-4/5 (dimer)/TRKB	-0.056	0.2	-10000	0	-0.43	112	112
neuron apoptosis	0.078	0.18	0.52	40	-10000	0	40
SHC 2-3/Grb2	-0.085	0.2	-10000	0	-0.58	40	40
SHC1	0.029	0.007	-10000	0	-10000	0	0
SHC2	-0.044	0.14	-10000	0	-0.5	24	24
SHC3	-0.11	0.23	-10000	0	-0.6	79	79
STAT3 (dimer)	0.027	0.053	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.007	0.16	-10000	0	-0.4	69	69
RIN/GDP	0.049	0.084	0.31	13	-0.32	4	17
GIPC1	0.029	0.029	-10000	0	-0.64	1	1
KRAS	0.029	0.006	-10000	0	-10000	0	0
DNAJA3	-0.03	0.11	-10000	0	-0.43	16	16
RIN/GTP	0.014	0.02	-10000	0	-0.44	1	1
CCND1	0.012	0.098	-10000	0	-0.51	18	18
MAGED1	0.03	0.003	-10000	0	-10000	0	0
PTPN11	0.029	0.005	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.017	0.056	-10000	0	-0.62	4	4
SHC/GRB2/SOS1	0.056	0.017	-10000	0	-10000	0	0
GRB2	0.029	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.053	0.2	-10000	0	-0.41	122	122
TRKA/NEDD4-2	0.006	0.13	-10000	0	-0.47	34	34
ELMO1	0.026	0.028	-10000	0	-0.59	1	1
RhoG/GTP/ELMO1/DOCK1	0.034	0.03	-10000	0	-0.39	2	2
NGF	-0.027	0.18	-10000	0	-0.59	47	47
HRAS	0.029	0.027	-10000	0	-0.59	1	1
DOCK1	0.028	0.03	-10000	0	-0.64	1	1
GAB2	0.03	0.003	-10000	0	-10000	0	0
RIT2	0.019	0.027	-10000	0	-0.59	1	1
RIT1	0.028	0.007	-10000	0	-10000	0	0
FRS2	0.029	0.005	-10000	0	-10000	0	0
DNM1	0.015	0.094	-10000	0	-0.6	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.005	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.014	0.11	-10000	0	-0.42	16	16
mol:GDP	0.056	0.12	0.41	14	-0.46	7	21
NGF (dimer)	-0.026	0.18	-10000	0	-0.59	47	47
RhoG/GDP	0.019	0.021	-10000	0	-0.44	1	1
RIT1/GDP	0.051	0.079	0.32	10	-0.31	4	14
TIAM1	0.029	0.006	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
BDNF (dimer)/TRKB	-0.076	0.22	-10000	0	-0.41	146	146
KIDINS220/CRKL/C3G	0.043	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.028	-10000	0	-0.47	1	1
FRS2 family/SHP2	0.056	0.017	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.07	0.023	-10000	0	-10000	0	0
RIT1/GTP	0.021	0.005	-10000	0	-10000	0	0
NT3 (dimer)	0.023	0.063	-10000	0	-0.62	5	5
RAP1/GDP	0.034	0.056	-10000	0	-0.28	2	2
KIDINS220/CRKL	0.03	0.004	-10000	0	-10000	0	0
BDNF (dimer)	-0.052	0.21	-10000	0	-0.59	69	69
ubiquitin-dependent protein catabolic process	-0.014	0.16	-10000	0	-0.38	79	79
Schwann cell development	-0.019	0.027	-10000	0	-10000	0	0
EHD4	0.03	0.003	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.07	0.023	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.042	0.024	-10000	0	-10000	0	0
RAP1B	0.029	0.005	-10000	0	-10000	0	0
RAP1A	0.029	0.006	-10000	0	-10000	0	0
CDC42/GTP	-0.062	0.2	-10000	0	-0.62	25	25
ABL1	0.029	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.043	0.01	-10000	0	-10000	0	0
Rap1/GTP	0	0.11	-10000	0	-0.49	7	7
STAT3	0.027	0.053	-10000	0	-10000	0	0
axon guidance	-0.069	0.18	-10000	0	-0.59	25	25
MAPK3	-0.062	0.18	-10000	0	-0.43	44	44
MAPK1	-0.061	0.18	-10000	0	-0.45	38	38
CDC42/GDP	0.057	0.086	0.33	16	-0.31	4	20
NTF3	0.023	0.063	-10000	0	-0.62	5	5
NTF4	0.017	0.056	-10000	0	-0.62	4	4
NGF (dimer)/TRKA/FAIM	-0.014	0.16	-10000	0	-0.39	79	79
PI3K	0.037	0.035	-10000	0	-0.47	2	2
FRS3	0.029	0.006	-10000	0	-10000	0	0
FAIM	0.028	0.007	-10000	0	-10000	0	0
GAB1	0.03	0.004	-10000	0	-10000	0	0
RASGRF1	-0.036	0.12	-10000	0	-0.45	19	19
SOS1	0.029	0.005	-10000	0	-10000	0	0
MCF2L	0.003	0.1	-10000	0	-0.43	26	26
RGS19	0.029	0.006	-10000	0	-10000	0	0
CDC42	0.029	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.049	0.096	0.33	3	-0.57	6	9
Rac1/GDP	0.046	0.074	0.3	6	-0.32	4	10
NGF (dimer)/TRKA/GRIT	-0.029	0.16	-10000	0	-0.39	80	80
neuron projection morphogenesis	0.001	0.16	0.41	1	-1.1	6	7
NGF (dimer)/TRKA/NEDD4-2	-0.014	0.16	-10000	0	-0.39	79	79
MAP2K1	0.041	0.047	0.43	3	-10000	0	3
NGFR	-0.011	0.16	-10000	0	-0.6	34	34
NGF (dimer)/TRKA/GIPC/GAIP	-0.007	0.11	-10000	0	-0.43	11	11
RAS family/GTP/PI3K	0.03	0.033	-10000	0	-0.45	2	2
FRS2 family/SHP2/GRB2/SOS1	0.08	0.028	-10000	0	-10000	0	0
NRAS	0.029	0.006	-10000	0	-10000	0	0
GRB2/SOS1	0.043	0.01	-10000	0	-10000	0	0
PRKCI	0.028	0.007	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCZ	0.025	0.05	-10000	0	-0.64	3	3
MAPKKK cascade	-0.064	0.2	-10000	0	-0.61	55	55
RASA1	0.025	0.03	-10000	0	-0.64	1	1
TRKA/c-Abl	0.006	0.13	-10000	0	-0.47	34	34
SQSTM1	0.022	0.013	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.058	0.2	-10000	0	-0.4	89	89
NGF (dimer)/TRKA/p62/Atypical PKCs	0.009	0.13	-10000	0	-0.65	1	1
MATK	-0.033	0.19	-10000	0	-0.59	53	53
NEDD4L	0.028	0.029	-10000	0	-0.64	1	1
RAS family/GDP	-0.008	0.034	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.032	0.12	-10000	0	-0.45	17	17
Rac1/GTP	-0.03	0.068	-10000	0	-0.36	5	5
FRS2 family/SHP2/CRK family	0.081	0.027	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0	0.16	0.38	2	-0.52	5	7
PTK2B	0.027	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.047	0.15	0.48	2	-0.79	5	7
EDN1	0.001	0.16	0.42	1	-0.5	22	23
EDN3	0.011	0.088	-10000	0	-0.59	11	11
EDN2	-0.047	0.2	-10000	0	-0.57	66	66
HRAS/GDP	0.032	0.15	0.32	5	-0.59	11	16
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.017	0.12	0.27	1	-0.54	10	11
ADCY4	0.004	0.13	0.34	1	-0.42	5	6
ADCY5	-0.01	0.15	0.35	2	-0.52	15	17
ADCY6	0.003	0.13	0.34	1	-0.44	6	7
ADCY7	-0.007	0.14	0.34	1	-0.47	9	10
ADCY1	-0.005	0.14	0.34	1	-0.48	6	7
ADCY2	-0.068	0.18	0.36	1	-0.46	30	31
ADCY3	0.006	0.13	0.35	2	-0.44	6	8
ADCY8	-0.093	0.19	0.34	1	-0.49	36	37
ADCY9	0.004	0.13	0.35	2	-0.44	6	8
arachidonic acid secretion	0.043	0.15	0.38	7	-0.56	12	19
ETB receptor/Endothelin-1/Gq/GTP	0.027	0.088	-10000	0	-0.5	6	6
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
HRAS	0.029	0.027	-10000	0	-0.59	1	1
ETA receptor/Endothelin-1/G12/GTP	0.037	0.18	0.4	20	-0.53	4	24
ETA receptor/Endothelin-1/Gs/GTP	0.039	0.17	0.38	23	-0.47	6	29
mol:GTP	0.002	0.002	-10000	0	-10000	0	0
COL3A1	-0.026	0.23	0.41	1	-0.66	49	50
EDNRB	0.018	0.056	-10000	0	-0.51	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.03	0.22	0.6	1	-0.54	46	47
CYSLTR1	0.002	0.17	0.41	1	-0.54	7	8
SLC9A1	0.013	0.097	0.28	2	-0.32	4	6
mol:GDP	0.023	0.16	0.32	8	-0.62	12	20
SLC9A3	-0.33	0.29	-10000	0	-0.67	132	132
RAF1	0.013	0.15	0.32	5	-0.62	12	17
JUN	0.048	0.14	-10000	0	-0.66	5	5
JAK2	0.001	0.17	0.38	2	-0.55	5	7
mol:IP3	0.012	0.13	0.26	1	-0.58	11	12
ETA receptor/Endothelin-1	0.026	0.23	0.47	24	-0.45	40	64
PLCB1	0.018	0.087	-10000	0	-0.64	9	9
PLCB2	-0.038	0.2	-10000	0	-0.59	58	58
ETA receptor/Endothelin-3	0.023	0.11	-10000	0	-0.44	11	11
FOS	0.029	0.18	0.39	4	-0.81	16	20
Gai/GDP	-0.1	0.25	-10000	0	-0.62	46	46
CRK	0.03	0.005	-10000	0	-10000	0	0
mol:Ca ++	-0.001	0.18	0.33	1	-0.6	14	15
BCAR1	0.028	0.03	-10000	0	-0.63	1	1
PRKCB1	0.014	0.13	-10000	0	-0.55	11	11
GNAQ	0.032	0.007	-10000	0	-10000	0	0
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
GNAL	0.029	0.005	-10000	0	-10000	0	0
Gs family/GDP	0.028	0.14	0.3	5	-0.58	10	15
ETA receptor/Endothelin-1/Gq/GTP	0.035	0.11	0.26	1	-0.49	5	6
MAPK14	0.014	0.1	0.35	1	-0.53	8	9
TRPC6	0.046	0.16	0.55	1	-0.91	4	5
GNAI2	0.021	0.014	-10000	0	-10000	0	0
GNAI3	0.029	0.006	-10000	0	-10000	0	0
GNAI1	0.026	0.03	-10000	0	-0.64	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.012	0.11	-10000	0	-0.5	12	12
ETB receptor/Endothelin-2	-0.025	0.16	-10000	0	-0.44	61	61
ETB receptor/Endothelin-3	0.02	0.08	-10000	0	-0.44	13	13
ETB receptor/Endothelin-1	0.014	0.14	-10000	0	-0.42	17	17
MAPK3	0.032	0.17	0.39	5	-0.73	16	21
MAPK1	0.032	0.18	0.4	5	-0.71	17	22
Rac1/GDP	0.024	0.14	0.31	2	-0.59	10	12
cAMP biosynthetic process	-0.024	0.15	0.42	6	-0.48	11	17
MAPK8	0.045	0.16	0.4	1	-0.68	11	12
SRC	0.029	0.006	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.012	0.073	-10000	0	-0.47	4	4
p130Cas/CRK/Src/PYK2	0.039	0.16	0.41	10	-0.62	11	21
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.024	0.14	0.31	2	-0.59	10	12
COL1A2	-0.025	0.24	0.64	1	-0.6	61	62
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.022	0.17	0.29	1	-0.44	60	61
mol:DAG	0.012	0.13	0.26	1	-0.58	11	12
MAP2K2	0.028	0.16	0.46	3	-0.62	15	18
MAP2K1	0.03	0.16	0.38	5	-0.64	13	18
EDNRA	0.022	0.12	0.41	1	-0.36	5	6
positive regulation of muscle contraction	0.021	0.15	0.42	7	-0.46	4	11
Gq family/GDP	0.036	0.15	-10000	0	-0.62	11	11
HRAS/GTP	0.018	0.15	0.32	5	-0.61	12	17
PRKCH	0.013	0.12	-10000	0	-0.58	8	8
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCA	0.019	0.13	-10000	0	-0.59	9	9
PRKCB	0.017	0.14	0.33	6	-0.61	12	18
PRKCE	0.016	0.13	-10000	0	-0.57	10	10
PRKCD	-0.002	0.12	-10000	0	-0.59	9	9
PRKCG	-0.001	0.15	-10000	0	-0.56	18	18
regulation of vascular smooth muscle contraction	0.028	0.21	0.42	5	-0.93	16	21
PRKCQ	0.007	0.14	0.29	1	-0.63	12	13
PLA2G4A	0.041	0.16	0.38	7	-0.61	12	19
GNA14	0.023	0.077	-10000	0	-0.63	7	7
GNA15	0.014	0.1	-10000	0	-0.59	15	15
GNA12	0.027	0.009	-10000	0	-10000	0	0
GNA11	0.028	0.05	-10000	0	-0.63	3	3
Rac1/GTP	0.038	0.18	0.41	19	-0.53	4	23
MMP1	-0.11	0.28	0.7	1	-0.63	103	104

×

IL6-mediated signaling events

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
BCL2L1	-0.094	0.24	0.57	3	-0.66	16	19
CRP	-0.13	0.29	0.55	1	-0.7	59	60
cell cycle arrest	-0.12	0.26	-10000	0	-0.68	41	41
TIMP1	-0.097	0.26	-10000	0	-0.68	33	33
IL6ST	0.003	0.12	-10000	0	-0.62	18	18
Rac1/GDP	-0.085	0.18	-10000	0	-0.47	39	39
AP1	0.029	0.12	0.46	1	-0.75	4	5
GAB2	0.03	0.003	-10000	0	-10000	0	0
TNFSF11	-0.13	0.28	0.61	1	-0.73	39	40
HSP90B1	0.026	0.064	-10000	0	-10000	0	0
GAB1	0.03	0.004	-10000	0	-10000	0	0
MAPK14	0.005	0.1	-10000	0	-0.54	6	6
AKT1	0.045	0.04	-10000	0	-0.5	1	1
FOXO1	0.054	0.044	-10000	0	-0.48	1	1
MAP2K6	-0.017	0.1	-10000	0	-0.58	6	6
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.099	0.19	-10000	0	-0.5	40	40
MITF	-0.027	0.1	-10000	0	-0.48	8	8
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.03	0.003	-10000	0	-10000	0	0
A2M	0.029	0.07	-10000	0	-1.1	2	2
CEBPB	0.024	0.077	-10000	0	-0.59	8	8
GRB2/SOS1/GAB family/SHP2	0.014	0.08	-10000	0	-0.66	4	4
STAT3	-0.14	0.26	-10000	0	-0.72	40	40
STAT1	0.001	0.1	-10000	0	-0.82	7	7
CEBPD	-0.096	0.24	0.55	2	-0.64	18	20
PIK3CA	0.029	0.03	-10000	0	-0.64	1	1
PI3K	0.04	0.035	-10000	0	-0.47	2	2
JUN	0.028	0.006	-10000	0	-10000	0	0
PIAS3/MITF	-0.012	0.11	-10000	0	-0.55	5	5
MAPK11	0.004	0.11	-10000	0	-0.58	7	7
STAT3 (dimer)/FOXO1	-0.063	0.21	0.43	1	-0.62	7	8
GRB2/SOS1/GAB family	0.028	0.12	-10000	0	-0.51	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.019	0.12	-10000	0	-0.43	16	16
GRB2	0.029	0.005	-10000	0	-10000	0	0
JAK2	0.028	0.007	-10000	0	-10000	0	0
LBP	-0.22	0.4	0.57	3	-0.8	138	141
PIK3R1	0.027	0.03	-10000	0	-0.63	1	1
JAK1	0.028	0.011	-10000	0	-10000	0	0
MYC	-0.1	0.25	0.54	3	-0.67	22	25
FGG	-0.18	0.31	0.52	1	-0.71	70	71
macrophage differentiation	-0.12	0.26	-10000	0	-0.68	41	41
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.005	0.15	-10000	0	-0.48	9	9
JUNB	-0.099	0.24	-10000	0	-0.68	19	19
FOS	0.012	0.099	-10000	0	-0.63	12	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.027	0.12	-10000	0	-0.46	11	11
STAT1/PIAS1	-0.031	0.13	-10000	0	-0.53	7	7
GRB2/SOS1/GAB family/SHP2/PI3K	0.042	0.043	-10000	0	-0.54	1	1
STAT3 (dimer)	-0.13	0.27	-10000	0	-0.71	41	41
PRKCD	-0.11	0.21	0.42	7	-0.57	34	41
IL6R	0.028	0.01	-10000	0	-10000	0	0
SOCS3	0.032	0.12	0.45	1	-0.62	4	5
gp130 (dimer)/JAK1/JAK1/LMO4	0.032	0.086	-10000	0	-0.4	17	17
Rac1/GTP	-0.093	0.18	-10000	0	-0.47	50	50
HCK	-0.004	0.14	-10000	0	-0.59	27	27
MAPKKK cascade	0.033	0.096	-10000	0	-0.78	3	3
bone resorption	-0.12	0.27	0.61	1	-0.69	39	40
IRF1	-0.066	0.26	0.56	6	-0.66	16	22
mol:GDP	-0.1	0.17	-10000	0	-0.44	60	60
SOS1	0.029	0.005	-10000	0	-10000	0	0
VAV1	-0.1	0.17	-10000	0	-0.44	60	60
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.006	0.12	-10000	0	-0.55	8	8
PTPN11	0.012	0.038	-10000	0	-0.7	1	1
IL6/IL6RA	-0.022	0.16	-10000	0	-0.45	61	61
gp130 (dimer)/TYK2/TYK2/LMO4	0.035	0.084	-10000	0	-0.4	17	17
gp130 (dimer)/JAK2/JAK2/LMO4	0.032	0.084	-10000	0	-0.4	17	17
IL6	-0.052	0.21	-10000	0	-0.61	62	62
PIAS3	0.029	0.006	-10000	0	-10000	0	0
PTPRE	0.029	0.031	-10000	0	-0.55	1	1
PIAS1	0.03	0.003	-10000	0	-10000	0	0
RAC1	0.026	0.009	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.02	0.1	-10000	0	-0.46	8	8
LMO4	0.025	0.017	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.12	0.25	-10000	0	-0.71	28	28
MCL1	0.06	0.057	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.023	0.034	-10000	0	-0.62	1	1
HSPA8	0.03	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.076	0.074	0.36	1	-0.4	4	5
AKT1	0.03	0.012	-10000	0	-10000	0	0
GSC	-0.028	0.16	-10000	0	-0.56	14	14
NKX2-5	0.003	0.001	-10000	0	-10000	0	0
muscle cell differentiation	-0.044	0.08	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.094	0.09	-10000	0	-10000	0	0
SMAD4	0.041	0.036	-10000	0	-10000	0	0
CBFB	0.029	0.006	-10000	0	-10000	0	0
SAP18	0.029	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.047	0.044	-10000	0	-0.37	3	3
SMAD3/SMAD4/VDR	0.091	0.061	-10000	0	-10000	0	0
MYC	0.004	0.12	-10000	0	-0.59	19	19
CDKN2B	0.022	0.11	-10000	0	-0.56	2	2
AP1	0.063	0.067	-10000	0	-0.39	1	1
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.054	0.065	-10000	0	-0.49	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.045	0.044	-10000	0	-10000	0	0
SP3	0.032	0.007	-10000	0	-10000	0	0
CREB1	0.029	0.006	-10000	0	-10000	0	0
FOXH1	-0.021	0.17	-10000	0	-0.6	40	40
SMAD3/SMAD4/GR	0.064	0.056	-10000	0	-0.39	1	1
GATA3	-0.3	0.33	-10000	0	-0.63	258	258
SKI/SIN3/HDAC complex/NCoR1	0.043	0.036	-10000	0	-0.36	1	1
MEF2C/TIF2	0.024	0.12	-10000	0	-0.65	3	3
endothelial cell migration	0.054	0.17	0.52	19	-10000	0	19
MAX	0.03	0.014	-10000	0	-10000	0	0
RBBP7	0.03	0.003	-10000	0	-10000	0	0
RBBP4	0.028	0.03	-10000	0	-0.64	1	1
RUNX2	0.012	0.1	-10000	0	-0.59	14	14
RUNX3	-0.24	0.31	-10000	0	-0.59	229	229
RUNX1	-0.013	0.15	-10000	0	-0.59	35	35
CTBP1	0.029	0.004	-10000	0	-10000	0	0
NR3C1	0.024	0.032	-10000	0	-0.59	1	1
VDR	0.025	0.05	-10000	0	-0.64	3	3
CDKN1A	0.05	0.082	-10000	0	-10000	0	0
KAT2B	0.02	0.031	-10000	0	-0.63	1	1
SMAD2/SMAD2/SMAD4/FOXH1	0.038	0.14	-10000	0	-0.4	33	33
DCP1A	0.022	0.013	-10000	0	-10000	0	0
SKI	0.029	0.007	-10000	0	-10000	0	0
SERPINE1	-0.054	0.17	-10000	0	-0.52	19	19
SMAD3/SMAD4/ATF2	0.073	0.05	-10000	0	-0.41	1	1
SMAD3/SMAD4/ATF3	0.071	0.062	-10000	0	-0.42	4	4
SAP30	0.008	0.11	-10000	0	-0.59	18	18
Cbp/p300/PIAS3	0.047	0.041	-10000	0	-0.38	1	1
JUN	0.051	0.064	-10000	0	-0.38	1	1
SMAD3/SMAD4/IRF7	0.063	0.092	-10000	0	-0.39	6	6
TFE3	0.029	0.021	-10000	0	-10000	0	0
COL1A2	-0.029	0.16	-10000	0	-0.47	58	58
mesenchymal cell differentiation	-0.063	0.085	0.39	11	-10000	0	11
DLX1	-0.29	0.31	-10000	0	-0.59	272	272
TCF3	0.03	0.003	-10000	0	-10000	0	0
FOS	0.02	0.099	-10000	0	-0.62	12	12
SMAD3/SMAD4/Max	0.079	0.049	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.053	0.028	-10000	0	-0.39	1	1
ZBTB17	0.024	0.04	-10000	0	-0.61	2	2
LAMC1	0.053	0.039	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.075	0.044	-10000	0	-10000	0	0
IRF7	0.009	0.12	-10000	0	-0.59	19	19
ESR1	0.024	0.06	-10000	0	-0.56	5	5
HNF4A	-0.019	0.17	-10000	0	-0.64	38	38
MEF2C	0.022	0.11	0.38	5	-0.42	5	10
SMAD2-3/SMAD4	0.083	0.049	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.051	0.031	-10000	0	-0.39	1	1
IGHV3OR16-13	-0.024	0.066	-10000	0	-0.49	5	5
TGIF2/HDAC complex	0.029	0.006	-10000	0	-10000	0	0
CREBBP	0.027	0.011	-10000	0	-10000	0	0
SKIL	0.028	0.007	-10000	0	-10000	0	0
HDAC1	0.029	0.006	-10000	0	-10000	0	0
HDAC2	0.028	0.008	-10000	0	-10000	0	0
SNIP1	0.029	0.006	-10000	0	-10000	0	0
GCN5L2	-0.002	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.079	0.054	-10000	0	-10000	0	0
MSG1/HSC70	0.043	0.03	-10000	0	-0.44	2	2
SMAD2	0.031	0.024	-10000	0	-10000	0	0
SMAD3	0.042	0.034	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.052	0.033	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.015	0.068	-10000	0	-0.45	4	4
NCOR1	0.029	0.005	-10000	0	-10000	0	0
NCOA2	0.015	0.091	-10000	0	-0.64	10	10
NCOA1	0.029	0.005	-10000	0	-10000	0	0
MYOD/E2A	0.012	0.11	-10000	0	-0.43	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.1	0.094	-10000	0	-10000	0	0
IFNB1	0.031	0.078	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.051	0.11	-10000	0	-10000	0	0
CITED1	0.027	0.038	-10000	0	-0.59	2	2
SMAD2-3/SMAD4/ARC105	0.097	0.047	-10000	0	-10000	0	0
RBL1	0.029	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.055	0.046	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.15	0.22	-10000	0	-0.39	241	241
SMAD7	0.08	0.068	-10000	0	-10000	0	0
MYC/MIZ-1	0.017	0.093	-10000	0	-0.43	21	21
SMAD3/SMAD4	0.015	0.094	-10000	0	-0.48	1	1
IL10	-0.16	0.24	-10000	0	-0.64	38	38
PIASy/HDAC complex	0.031	0.009	-10000	0	-10000	0	0
PIAS3	0.028	0.007	-10000	0	-10000	0	0
CDK2	0.027	0.01	-10000	0	-10000	0	0
IL5	-0.13	0.19	-10000	0	-0.55	17	17
CDK4	0.025	0.014	-10000	0	-10000	0	0
PIAS4	0.031	0.009	-10000	0	-10000	0	0
ATF3	0.023	0.06	-10000	0	-0.57	5	5
SMAD3/SMAD4/SP1	0.07	0.087	-10000	0	-0.38	1	1
FOXG1	-0.01	0.11	-10000	0	-0.59	18	18
FOXO3	0.024	0.013	-10000	0	-10000	0	0
FOXO1	0.025	0.012	-10000	0	-10000	0	0
FOXO4	0.026	0.011	-10000	0	-10000	0	0
heart looping	0.022	0.11	0.38	5	-0.41	7	12
CEBPB	0.021	0.077	-10000	0	-0.59	8	8
SMAD3/SMAD4/DLX1	-0.16	0.22	-10000	0	-0.38	251	251
MYOD1	-0.012	0.14	-10000	0	-0.59	29	29
SMAD3/SMAD4/HNF4	0.04	0.14	-10000	0	-0.42	38	38
SMAD3/SMAD4/GATA3	-0.16	0.25	-10000	0	-0.41	218	218
SnoN/SIN3/HDAC complex/NCoR1	0.028	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.1	0.21	-10000	0	-0.55	22	22
SMAD3/SMAD4/SP1-3	0.087	0.085	-10000	0	-10000	0	0
MED15	0.03	0.004	-10000	0	-10000	0	0
SP1	0.023	0.05	-10000	0	-10000	0	0
SIN3B	0.03	0.003	-10000	0	-10000	0	0
SIN3A	0.03	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.043	0.12	-10000	0	-0.43	14	14
ITGB5	0.058	0.077	0.43	2	-10000	0	2
TGIF/SIN3/HDAC complex/CtBP	0.039	0.05	-10000	0	-0.47	3	3
SMAD3/SMAD4/AR	0.055	0.11	-10000	0	-0.42	25	25
AR	-0.002	0.14	-10000	0	-0.62	26	26
negative regulation of cell growth	0.055	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.048	0.11	-10000	0	-0.38	27	27
E2F5	0.027	0.03	-10000	0	-0.64	1	1
E2F4	0.029	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.039	0.12	-10000	0	-0.43	12	12
SMAD2-3/SMAD4/FOXO1-3a-4	0.053	0.036	-10000	0	-10000	0	0
TFDP1	0.029	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.082	0.071	-10000	0	-0.39	1	1
SMAD3/SMAD4/RUNX2	0.063	0.085	-10000	0	-0.39	11	11
TGIF2	0.029	0.006	-10000	0	-10000	0	0
TGIF1	0.029	0.005	-10000	0	-10000	0	0
ATF2	0.027	0.03	-10000	0	-0.64	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.037	0.077	-10000	0	-0.63	1	1
HDAC1	0.026	0.008	-10000	0	-10000	0	0
AES	0.029	0.004	-10000	0	-10000	0	0
FBXW11	0.023	0.013	-10000	0	-10000	0	0
DTX1	-0.027	0.18	-10000	0	-0.63	45	45
LRP6/FZD1	0.039	0.015	-10000	0	-10000	0	0
TLE1	0.028	0.006	-10000	0	-10000	0	0
AP1	-0.065	0.16	-10000	0	-0.32	136	136
NCSTN	0.029	0.007	-10000	0	-10000	0	0
ADAM10	0.028	0.029	-10000	0	-0.64	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.046	0.062	-10000	0	-0.74	1	1
NICD/RBPSUH	0.04	0.077	-10000	0	-0.61	1	1
WIF1	0.016	0.064	-10000	0	-0.63	5	5
NOTCH1	0.025	0.075	-10000	0	-0.65	1	1
PSENEN	0.03	0.003	-10000	0	-10000	0	0
KREMEN2	-0.043	0.2	-10000	0	-0.59	60	60
DKK1	0.002	0.13	-10000	0	-0.61	22	22
beta catenin/beta TrCP1	0.036	0.091	0.3	4	-10000	0	4
APH1B	0.03	0.003	-10000	0	-10000	0	0
APH1A	0.029	0.007	-10000	0	-10000	0	0
AXIN1	0.011	0.066	0.28	3	-0.32	1	4
CtBP/CBP/TCF1/TLE1/AES	0.028	0.038	-10000	0	-0.36	2	2
PSEN1	0.028	0.008	-10000	0	-10000	0	0
FOS	0.013	0.099	-10000	0	-0.63	12	12
JUN	0.029	0.006	-10000	0	-10000	0	0
MAP3K7	0.027	0.008	-10000	0	-10000	0	0
CTNNB1	0.036	0.11	0.29	12	-0.33	4	16
MAPK3	0.029	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.009	0.15	-10000	0	-0.38	75	75
HNF1A	0.023	0.058	-10000	0	-0.64	4	4
CTBP1	0.029	0.004	-10000	0	-10000	0	0
MYC	0.007	0.14	-10000	0	-0.7	10	10
NKD1	-0.14	0.29	-10000	0	-0.63	134	134
FZD1	0.027	0.009	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.009	0.13	-10000	0	-0.6	4	4
apoptosis	-0.065	0.16	-10000	0	-0.32	136	136
Delta 1/NOTCHprecursor	0.037	0.077	-10000	0	-0.61	1	1
DLL1	0.027	0.008	-10000	0	-10000	0	0
PPARD	0.009	0.15	-10000	0	-0.75	19	19
Gamma Secretase	0.079	0.029	-10000	0	-10000	0	0
APC	0.011	0.072	0.3	3	-0.4	3	6
DVL1	0.02	0.035	-10000	0	-0.43	2	2
CSNK2A1	0.029	0.006	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.008	0.16	-10000	0	-0.4	69	69
LRP6	0.029	0.006	-10000	0	-10000	0	0
CSNK1A1	0.023	0.013	-10000	0	-10000	0	0
NLK	0.017	0.009	-10000	0	-10000	0	0
CCND1	0.02	0.099	-10000	0	-0.57	5	5
WNT1	-0.001	0.13	-10000	0	-0.59	25	25
Axin1/APC/beta catenin	0.081	0.099	0.4	17	-10000	0	17
DKK2	0	0.13	-10000	0	-0.6	24	24
NOTCH1 precursor/DVL1	0.046	0.081	-10000	0	-0.55	1	1
GSK3B	0.028	0.008	-10000	0	-10000	0	0
FRAT1	0.028	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.01	0.13	-10000	0	-0.61	4	4
PPP2R5D	0.084	0.15	0.34	119	-0.37	9	128
MAPK1	0.03	0.004	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.041	0.096	-10000	0	-0.34	29	29
RBPJ	0.029	0.004	-10000	0	-10000	0	0
CREBBP	0.031	0.009	-10000	0	-10000	0	0

×

LPA receptor mediated 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
GNB1/GNG2	0.037	0.089	-10000	0	-0.36	22	22
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.078	-10000	0	-10000	0	0
AP1	0.019	0.097	-10000	0	-0.39	4	4
mol:PIP3	-0.003	0.067	-10000	0	-0.49	1	1
AKT1	0.01	0.11	0.38	2	-0.4	1	3
PTK2B	0.005	0.086	0.26	1	-0.39	8	9
RHOA	-0.04	0.12	-10000	0	-0.38	22	22
PIK3CB	0.028	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.028	0.059	0.42	2	-0.39	2	4
MAGI3	0.025	0.05	-10000	0	-0.63	3	3
RELA	0.03	0.003	-10000	0	-10000	0	0
apoptosis	0.009	0.079	-10000	0	-0.33	23	23
HRAS/GDP	0.021	0.02	-10000	0	-0.44	1	1
positive regulation of microtubule depolymerization	0.01	0.087	0.28	4	-0.34	8	12
NF kappa B1 p50/RelA	0.026	0.079	-10000	0	-10000	0	0
endothelial cell migration	0.005	0.1	-10000	0	-0.42	28	28
ADCY4	0.004	0.1	-10000	0	-0.45	22	22
ADCY5	-0.001	0.11	-10000	0	-0.44	27	27
ADCY6	0.004	0.1	-10000	0	-0.45	22	22
ADCY7	0.001	0.1	-10000	0	-0.45	22	22
ADCY1	0.001	0.1	-10000	0	-0.44	22	22
ADCY2	-0.025	0.12	-10000	0	-0.44	27	27
ADCY3	0.004	0.1	-10000	0	-0.44	23	23
ADCY8	-0.032	0.12	-10000	0	-0.44	28	28
ADCY9	0.003	0.1	-10000	0	-0.45	22	22
GSK3B	0.008	0.083	0.28	4	-0.38	7	11
arachidonic acid secretion	0.006	0.1	-10000	0	-0.44	22	22
GNG2	0.028	0.008	-10000	0	-10000	0	0
TRIP6	0.029	0.012	-10000	0	-10000	0	0
GNAO1	0.006	0.095	-10000	0	-0.38	27	27
HRAS	0.029	0.027	-10000	0	-0.59	1	1
NFKBIA	0.032	0.076	0.36	4	-0.39	1	5
GAB1	0.03	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.016	0.17	-10000	0	-0.82	19	19
JUN	0.029	0.006	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.039	0.025	-10000	0	-0.4	1	1
TIAM1	-0.001	0.2	-10000	0	-0.98	20	20
PIK3R1	0.026	0.03	-10000	0	-0.63	1	1
mol:IP3	0.027	0.059	0.42	2	-0.4	2	4
PLCB3	0.035	0.039	-10000	0	-0.36	1	1
FOS	0.013	0.099	-10000	0	-0.63	12	12
positive regulation of mitosis	0.006	0.1	-10000	0	-0.44	22	22
LPA/LPA1-2-3	0.035	0.095	-10000	0	-0.36	25	25
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
stress fiber formation	0.018	0.087	0.38	1	-0.37	6	7
GNAZ	0.007	0.096	-10000	0	-0.4	25	25
EGFR/PI3K-beta/Gab1	0.009	0.074	-10000	0	-0.51	1	1
positive regulation of dendritic cell cytokine production	0.033	0.094	-10000	0	-0.36	25	25
LPA/LPA2/MAGI-3	0.037	0.037	-10000	0	-0.4	3	3
ARHGEF1	0.032	0.092	0.37	6	-0.33	15	21
GNAI2	0.003	0.085	-10000	0	-0.37	23	23
GNAI3	0.009	0.09	-10000	0	-0.39	22	22
GNAI1	0.009	0.084	-10000	0	-0.38	20	20
LPA/LPA3	0.017	0.038	-10000	0	-0.43	3	3
LPA/LPA2	0.024	0.016	-10000	0	-10000	0	0
LPA/LPA1	0.005	0.1	-10000	0	-0.42	28	28
HB-EGF/EGFR	-0.13	0.19	-10000	0	-0.37	182	182
HBEGF	-0.16	0.21	-10000	0	-0.43	187	187
mol:DAG	0.027	0.059	0.42	2	-0.4	2	4
cAMP biosynthetic process	0.011	0.12	0.36	10	-0.42	18	28
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
SRC	0.029	0.006	-10000	0	-10000	0	0
GNB1	0.028	0.006	-10000	0	-10000	0	0
LYN	0.034	0.08	0.36	5	-0.41	1	6
GNAQ	0.022	0.026	-10000	0	-10000	0	0
LPAR2	0.03	0.003	-10000	0	-10000	0	0
LPAR3	0.02	0.047	-10000	0	-0.59	3	3
LPAR1	0.003	0.13	-10000	0	-0.58	24	24
IL8	-0.033	0.15	0.3	1	-0.43	19	20
PTK2	0.013	0.083	-10000	0	-0.35	12	12
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
CASP3	0.009	0.079	-10000	0	-0.33	23	23
EGFR	0.02	0.067	-10000	0	-0.6	6	6
PLCG1	0.02	0.041	-10000	0	-0.37	2	2
PLD2	0.014	0.083	-10000	0	-0.34	20	20
G12/G13	0.038	0.081	-10000	0	-0.36	15	15
PI3K-beta	-0.023	0.1	-10000	0	-0.43	11	11
cell migration	0.028	0.065	-10000	0	-0.26	10	10
SLC9A3R2	0.027	0.03	-10000	0	-0.64	1	1
PXN	0.018	0.088	0.38	1	-0.38	6	7
HRAS/GTP	0.003	0.1	-10000	0	-0.45	22	22
RAC1	0.027	0.009	-10000	0	-10000	0	0
MMP9	-0.25	0.31	-10000	0	-0.59	234	234
PRKCE	0.028	0.03	-10000	0	-0.64	1	1
PRKCD	0.024	0.063	0.36	4	-0.39	1	5
Gi(beta/gamma)	0.009	0.1	-10000	0	-0.42	22	22
mol:LPA	0.001	0.022	-10000	0	-0.28	1	1
TRIP6/p130 Cas/FAK1/Paxillin	0.035	0.089	-10000	0	-10000	0	0
MAPKKK cascade	0.006	0.1	-10000	0	-0.44	22	22
contractile ring contraction involved in cytokinesis	-0.044	0.12	-10000	0	-0.37	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.017	0.051	-10000	0	-0.38	6	6
GNA15	0.015	0.054	-10000	0	-0.46	1	1
GNA12	0.027	0.009	-10000	0	-10000	0	0
GNA13	0.029	0.005	-10000	0	-10000	0	0
MAPT	0.01	0.089	0.28	4	-0.35	8	12
GNA11	0.021	0.037	-10000	0	-0.34	3	3
Rac1/GTP	0.016	0.18	-10000	0	-0.87	19	19
MMP2	0.005	0.1	-10000	0	-0.42	28	28

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.022	0.066	-10000	0	-0.59	6	6
GNB1/GNG2	-0.027	0.054	-10000	0	-0.2	18	18
AKT1	0.027	0.11	0.29	7	-0.35	12	19
EGF	-0.57	0.2	-10000	0	-0.63	474	474
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.013	0.075	0.34	3	-0.4	2	5
mol:Ca2+	0.038	0.12	0.33	6	-0.33	16	22
LYN	0.013	0.069	0.37	2	-10000	0	2
RhoA/GTP	0.008	0.047	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.035	0.13	0.34	6	-0.36	16	22
GNG2	0.028	0.008	-10000	0	-10000	0	0
ARRB2	0.028	0.032	-10000	0	-0.71	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.016	0.078	0.36	1	-0.48	5	6
G beta5/gamma2	-0.034	0.07	-10000	0	-0.27	19	19
PRKCH	0.032	0.13	0.38	3	-0.38	16	19
DNM1	0.015	0.094	-10000	0	-0.6	12	12
TXA2/TP beta/beta Arrestin3	0.003	0.036	-10000	0	-0.42	1	1
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.061	0.22	-10000	0	-0.59	75	75
G12 family/GTP	0.009	0.1	-10000	0	-0.32	13	13
ADRBK1	0.03	0.003	-10000	0	-10000	0	0
ADRBK2	0.03	0.004	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.029	0.019	-10000	0	-10000	0	0
mol:GDP	-0.032	0.091	0.42	4	-0.31	3	7
mol:NADP	0.027	0.009	-10000	0	-10000	0	0
RAB11A	0.03	0.003	-10000	0	-10000	0	0
PRKG1	0.011	0.11	-10000	0	-0.64	14	14
mol:IP3	0.036	0.14	0.39	4	-0.41	19	23
cell morphogenesis	0.028	0.019	-10000	0	-10000	0	0
PLCB2	0.03	0.18	0.5	2	-0.55	22	24
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.006	0.1	0.37	2	-0.4	15	17
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.002	0.095	0.39	1	-0.39	9	10
RHOA	0.021	0.014	-10000	0	-10000	0	0
PTGIR	0.027	0.04	-10000	0	-0.61	2	2
PRKCB1	0.033	0.14	0.37	4	-0.38	28	32
GNAQ	0.029	0.006	-10000	0	-10000	0	0
mol:L-citrulline	0.027	0.009	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.03	0.18	0.46	3	-0.52	37	40
LCK	0.004	0.097	0.34	3	-0.4	12	15
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.007	0.079	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.014	0.084	-10000	0	-0.46	9	9
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.011	0.081	-10000	0	-0.35	1	1
MAPK14	0.035	0.097	0.28	10	-0.26	1	11
TGM2/GTP	0.035	0.16	0.38	2	-0.46	13	15
MAPK11	0.037	0.097	0.28	10	-0.3	3	13
ARHGEF1	0.021	0.068	-10000	0	-0.23	1	1
GNAI2	0.021	0.014	-10000	0	-10000	0	0
JNK cascade	0.036	0.14	0.4	4	-0.38	34	38
RAB11/GDP	0.029	0.003	-10000	0	-10000	0	0
ICAM1	0.036	0.12	0.32	5	-0.32	19	24
cAMP biosynthetic process	0.032	0.14	0.35	6	-0.38	18	24
Gq family/GTP/EBP50	0.018	0.054	0.23	3	-0.28	4	7
actin cytoskeleton reorganization	0.028	0.019	-10000	0	-10000	0	0
SRC	0.012	0.067	0.39	1	-10000	0	1
GNB5	0.03	0.003	-10000	0	-10000	0	0
GNB1	0.029	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.1	0.086	0.27	2	-0.32	18	20
VCAM1	0.034	0.12	0.31	6	-0.35	16	22
TP beta/Gq family/GDP/G beta5/gamma2	0.016	0.078	0.36	1	-0.48	5	6
platelet activation	0.047	0.13	0.34	12	-0.33	10	22
PGI2/IP	0.02	0.03	-10000	0	-0.46	2	2
PRKACA	-0.008	0.084	-10000	0	-0.32	2	2
Gq family/GDP/G beta5/gamma2	0.013	0.075	0.26	1	-0.44	5	6
TXA2/TP beta/beta Arrestin2	0.001	0.051	-10000	0	-0.39	4	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.008	0.078	-10000	0	-0.3	2	2
mol:DAG	0.035	0.16	0.42	3	-0.43	29	32
EGFR	0.02	0.067	-10000	0	-0.6	6	6
TXA2/TP alpha	0.033	0.18	0.47	3	-0.51	20	23
Gq family/GTP	0.012	0.051	0.22	1	-0.31	7	8
YES1	0.015	0.071	0.37	2	-10000	0	2
GNAI2/GTP	0.001	0.067	-10000	0	-10000	0	0
PGD2/DP	-0.045	0.16	-10000	0	-0.44	75	75
SLC9A3R1	0.029	0.005	-10000	0	-10000	0	0
FYN	0.013	0.07	0.34	3	-10000	0	3
mol:NO	0.027	0.009	-10000	0	-10000	0	0
GNA15	0.012	0.1	-10000	0	-0.59	15	15
PGK/cGMP	0.024	0.069	-10000	0	-0.41	12	12
RhoA/GDP	0.021	0.013	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.024	0.092	-10000	0	-0.45	1	1
NOS3	0.027	0.009	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCA	0.036	0.13	0.37	6	-0.39	12	18
PRKCB	0.037	0.14	0.35	12	-0.4	20	32
PRKCE	0.036	0.14	0.34	5	-0.39	16	21
PRKCD	0.011	0.13	0.41	3	-0.39	26	29
PRKCG	0.029	0.15	0.42	3	-0.43	25	28
muscle contraction	0.034	0.17	0.46	3	-0.48	33	36
PRKCZ	0.035	0.13	0.35	5	-0.36	15	20
ARR3	0.021	0.005	-10000	0	-10000	0	0
TXA2/TP beta	0.019	0.082	-10000	0	-10000	0	0
PRKCQ	0.03	0.14	0.37	5	-0.41	18	23
MAPKKK cascade	0.031	0.16	0.43	3	-0.47	25	28
SELE	0.028	0.14	0.33	5	-0.41	36	41
TP beta/GNAI2/GDP/G beta/gamma	0.015	0.082	-10000	0	-10000	0	0
ROCK1	0.029	0.005	-10000	0	-10000	0	0
GNA14	0.02	0.076	-10000	0	-0.64	7	7
chemotaxis	0.028	0.2	0.52	2	-0.6	37	39
GNA12	0.027	0.009	-10000	0	-10000	0	0
GNA13	0.029	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.05	-10000	0	-0.64	3	3
Rac1/GTP	0.02	0.007	-10000	0	-10000	0	0

×

Aurora A signaling

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
Aurora A/GADD45A	0.037	0.04	-10000	0	-10000	0	0
BIRC5	-0.15	0.28	-10000	0	-0.59	149	149
NFKBIA	0.024	0.026	0.26	1	-10000	0	1
CPEB1	-0.1	0.26	-10000	0	-0.63	106	106
AKT1	0.023	0.024	-10000	0	-10000	0	0
NDEL1	0.029	0.005	-10000	0	-10000	0	0
Aurora A/BRCA1	0.031	0.035	-10000	0	-10000	0	0
NDEL1/TACC3	0.047	0.053	-10000	0	-0.46	3	3
GADD45A	0.029	0.006	-10000	0	-10000	0	0
GSK3B	0.031	0.013	-10000	0	-10000	0	0
PAK1/Aurora A	0.039	0.041	-10000	0	-10000	0	0
MDM2	0.029	0.005	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.072	0.19	-10000	0	-0.43	110	110
TP53	0.033	0.025	-10000	0	-0.34	1	1
DLG7	0.021	0.025	-10000	0	-10000	0	0
AURKAIP1	0.025	0.049	-10000	0	-0.62	3	3
ARHGEF7	0.029	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.05	0.056	-10000	0	-0.48	3	3
G2/M transition of mitotic cell cycle	0.031	0.034	-10000	0	-10000	0	0
AURKA	0.031	0.033	-10000	0	-10000	0	0
AURKB	-0.066	0.093	-10000	0	-0.18	155	155
CDC25B	0.029	0.032	-10000	0	-0.34	1	1
G2/M transition checkpoint	0.013	0.03	-10000	0	-10000	0	0
mRNA polyadenylation	-0.047	0.16	-10000	0	-0.36	103	103
Aurora A/CPEB	-0.047	0.16	-10000	0	-0.36	103	103
Aurora A/TACC1/TRAP/chTOG	0.063	0.045	-10000	0	-10000	0	0
BRCA1	0.029	0.004	-10000	0	-10000	0	0
centrosome duplication	0.038	0.041	-10000	0	-10000	0	0
regulation of centrosome cycle	0.045	0.052	-10000	0	-0.45	3	3
spindle assembly	0.061	0.044	-10000	0	-10000	0	0
TDRD7	0.029	0.006	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	-0.036	0.16	-10000	0	-0.41	13	13
CENPA	-0.049	0.085	-10000	0	-0.26	14	14
Aurora A/PP2A	0.037	0.04	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.03	0.031	-10000	0	-10000	0	0
negative regulation of DNA binding	0.033	0.027	-10000	0	-0.34	1	1
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.043	0.008	-10000	0	-10000	0	0
RASA1	0.025	0.03	-10000	0	-0.64	1	1
Ajuba/Aurora A	0.013	0.03	-10000	0	-10000	0	0
mitotic prometaphase	0.023	0.028	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.033	-10000	0	-10000	0	0
TACC1	0.027	0.009	-10000	0	-10000	0	0
TACC3	0.025	0.054	-10000	0	-0.59	4	4
Aurora A/Antizyme1	0.049	0.052	-10000	0	-0.34	3	3
Aurora A/RasGAP	0.034	0.044	-10000	0	-0.4	1	1
OAZ1	0.028	0.027	-10000	0	-0.59	1	1
RAN	0.029	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.033	0.01	-10000	0	-10000	0	0
GIT1	0.029	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.059	0.012	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.071	0.19	-10000	0	-0.43	110	110
PPP2R5D	0.029	0.006	-10000	0	-10000	0	0
Aurora A/TPX2	-0.045	0.15	-10000	0	-0.39	15	15
PAK1	0.03	0.003	-10000	0	-10000	0	0
CKAP5	0.03	0.003	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.013	0.058	-10000	0	-0.41	3	3
epithelial cell differentiation	0.027	0.071	-10000	0	-0.34	14	14
CYFIP2	0.014	0.077	-10000	0	-0.64	7	7
ENAH	0.062	0.1	0.39	17	-10000	0	17
EGFR	0.02	0.067	-10000	0	-0.6	6	6
EPHA2	0.027	0.03	-10000	0	-0.64	1	1
MYO6	0.058	0.11	0.38	13	-0.48	2	15
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.038	0.058	-10000	0	-0.4	7	7
AQP5	-0.1	0.24	-10000	0	-0.51	108	108
CTNND1	0.03	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.062	0.11	0.4	13	-10000	0	13
regulation of calcium-dependent cell-cell adhesion	0.052	0.12	0.4	11	-0.46	1	12
EGF	-0.57	0.2	-10000	0	-0.63	474	474
NCKAP1	0.029	0.006	-10000	0	-10000	0	0
AQP3	0.007	0.16	-10000	0	-0.55	30	30
cortical microtubule organization	0.027	0.071	-10000	0	-0.34	14	14
GO:0000145	0.052	0.11	0.39	13	-10000	0	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.031	0.073	-10000	0	-0.34	14	14
MLLT4	0.027	0.008	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.046	-10000	0	-10000	0	0
ARF6	0.028	0.008	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.065	0.041	-10000	0	-0.36	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.041	0.084	0.38	2	-10000	0	2
PVRL2	0.03	0.003	-10000	0	-10000	0	0
ZYX	0.048	0.094	0.36	5	-10000	0	5
ARF6/GTP	0.069	0.044	-10000	0	-0.34	2	2
CDH1	0.007	0.12	-10000	0	-0.62	18	18
EGFR/EGFR/EGF/EGF	-0.24	0.14	-10000	0	-0.59	19	19
RhoA/GDP	0.029	0.068	-10000	0	-10000	0	0
actin cytoskeleton organization	0.051	0.1	0.35	12	-0.45	2	14
IGF-1R heterotetramer	0.03	0.003	-10000	0	-10000	0	0
GIT1	0.029	0.004	-10000	0	-10000	0	0
IGF1R	0.03	0.003	-10000	0	-10000	0	0
IGF1	0.023	0.06	-10000	0	-0.59	5	5
DIAPH1	0.032	0.11	-10000	0	-0.67	7	7
Wnt receptor signaling pathway	-0.027	0.071	0.34	14	-10000	0	14
RHOA	0.021	0.014	-10000	0	-10000	0	0
RhoA/GTP	-0.009	0.048	-10000	0	-10000	0	0
CTNNA1	0.023	0.013	-10000	0	-10000	0	0
VCL	0.051	0.1	0.35	12	-0.46	2	14
EFNA1	0.027	0.028	-10000	0	-0.59	1	1
LPP	0.046	0.095	0.39	6	-10000	0	6
Ephrin A1/EPHA2	0.023	0.065	-10000	0	-10000	0	0
SEC6/SEC8	0.001	0.05	-10000	0	-10000	0	0
MGAT3	0.053	0.12	0.41	11	-0.47	1	12
HGF/MET	0.012	0.09	-10000	0	-0.6	3	3
HGF	0.003	0.12	-10000	0	-0.6	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.013	0.058	-10000	0	-0.41	3	3
actin cable formation	0.11	0.13	0.33	73	-10000	0	73
KIAA1543	0.048	0.11	0.36	10	-0.53	2	12
KIFC3	0.051	0.094	-10000	0	-10000	0	0
NCK1	0.027	0.03	-10000	0	-0.64	1	1
EXOC3	0.027	0.009	-10000	0	-10000	0	0
ACTN1	0.052	0.1	0.43	7	-10000	0	7
NCK1/GIT1	0.04	0.025	-10000	0	-0.47	1	1
mol:GDP	0.027	0.071	-10000	0	-0.34	14	14
EXOC4	0.027	0.009	-10000	0	-10000	0	0
STX4	0.051	0.092	-10000	0	-10000	0	0
PIP5K1C	0.062	0.11	0.4	13	-10000	0	13
LIMA1	0.029	0.005	-10000	0	-10000	0	0
ABI1	0.029	0.004	-10000	0	-10000	0	0
ROCK1	0.075	0.11	0.41	19	-10000	0	19
adherens junction assembly	0.071	0.14	0.51	16	-0.71	2	18
IGF-1R heterotetramer/IGF1	0.022	0.069	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.04	0.013	-10000	0	-10000	0	0
MET	0.024	0.039	-10000	0	-0.59	2	2
PLEKHA7	0.057	0.11	0.36	10	-0.56	2	12
mol:GTP	0.063	0.04	-10000	0	-0.35	3	3
establishment of epithelial cell apical/basal polarity	0.083	0.13	0.38	50	-10000	0	50
cortical actin cytoskeleton stabilization	0.013	0.058	-10000	0	-0.41	3	3
regulation of cell-cell adhesion	0.051	0.1	0.35	12	-0.45	2	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.013	0.058	-10000	0	-0.41	3	3

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.024	0.029	-10000	0	-10000	0	0
DAPP1	0.009	0.11	0.34	8	-0.41	13	21
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.08	0.19	0.29	1	-0.51	45	46
mol:DAG	-0.021	0.15	0.29	55	-0.26	37	92
HRAS	0.033	0.028	-10000	0	-0.59	1	1
RAP1A	0.033	0.009	-10000	0	-10000	0	0
ARF5/GDP	0.031	0.076	0.26	2	-0.38	4	6
PLCG2	0.02	0.073	-10000	0	-0.61	7	7
PLCG1	0.029	0.006	-10000	0	-10000	0	0
ARF5	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0.01	0.03	0.3	2	-10000	0	2
ARF1/GTP	0.037	0.057	0.31	3	-10000	0	3
RHOA	0.021	0.014	-10000	0	-10000	0	0
YES1	0.029	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.021	0.028	0.3	1	-10000	0	1
ADAP1	0.034	0.07	0.29	3	-10000	0	3
ARAP3	0.01	0.03	0.3	2	-10000	0	2
INPPL1	0.03	0.003	-10000	0	-10000	0	0
PREX1	0.029	0.006	-10000	0	-10000	0	0
ARHGEF6	0.03	0.003	-10000	0	-10000	0	0
ARHGEF7	0.029	0.004	-10000	0	-10000	0	0
ARF1	0.029	0.006	-10000	0	-10000	0	0
NRAS	0.033	0.01	-10000	0	-10000	0	0
FYN	0.028	0.008	-10000	0	-10000	0	0
ARF6	0.028	0.008	-10000	0	-10000	0	0
FGR	0.025	0.047	-10000	0	-0.59	3	3
mol:Ca2+	0	0.097	0.32	19	-10000	0	19
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.029	0.006	-10000	0	-10000	0	0
ZAP70	-0.31	0.31	-10000	0	-0.59	291	291
mol:IP3	-0.009	0.12	0.33	22	-10000	0	22
LYN	0.028	0.007	-10000	0	-10000	0	0
ARF1/GDP	0.042	0.081	0.26	6	-0.37	4	10
RhoA/GDP	0.018	0.046	0.38	1	-10000	0	1
PDK1/Src/Hsp90	0.052	0.029	-10000	0	-0.4	1	1
BLNK	0.028	0.03	-10000	0	-0.64	1	1
actin cytoskeleton reorganization	0.04	0.098	0.38	12	-10000	0	12
SRC	0.029	0.006	-10000	0	-10000	0	0
PLEKHA2	0.013	0.034	-10000	0	-0.37	4	4
RAC1	0.027	0.009	-10000	0	-10000	0	0
PTEN	0.021	0.013	-10000	0	-10000	0	0
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
ARF6/GTP	0.024	0.027	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.03	0.3	2	-10000	0	2
Src family/SYK family/BLNK-LAT	-0.1	0.17	-10000	0	-0.43	63	63
BLK	-0.013	0.15	-10000	0	-0.59	34	34
PDPK1	0.027	0.03	-10000	0	-0.64	1	1
CYTH1	0.048	0.073	0.29	11	-10000	0	11
HCK	-0.003	0.14	-10000	0	-0.59	27	27
CYTH3	0.037	0.063	0.29	3	-10000	0	3
CYTH2	0.047	0.072	0.29	11	-10000	0	11
KRAS	0.033	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.043	0.056	-10000	0	-0.42	1	1
SGK1	0.038	0.072	-10000	0	-0.45	1	1
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
mol:GDP	0.031	0.083	0.26	8	-0.4	4	12
SOS1	0.029	0.005	-10000	0	-10000	0	0
SYK	0.027	0.033	-10000	0	-0.48	2	2
ARF6/GDP	0.018	0.045	0.39	1	-10000	0	1
mol:PI-3-4-5-P3	0.039	0.062	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0.021	0.028	0.3	1	-10000	0	1
VAV1	-0.12	0.26	-10000	0	-0.59	123	123
mol:PI-3-4-P2	0.019	0.04	-10000	0	-0.43	4	4
RAS family/GTP/PI3K Class I	0.08	0.066	0.34	1	-10000	0	1
PLEKHA1	0.013	0.034	-10000	0	-0.37	4	4
Rac1/GDP	0.031	0.075	0.24	1	-0.38	4	5
LAT	-0.14	0.28	-10000	0	-0.59	144	144
Rac1/GTP	0.016	0.073	-10000	0	-0.4	1	1
ITK	-0.056	0.15	0.33	3	-10000	0	3
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.047	0.18	0.3	48	-0.38	39	87
LCK	0.003	0.12	-10000	0	-0.59	22	22
BTK	-0.015	0.15	0.29	12	-10000	0	12

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.081	0.17	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.03	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.05	0.15	-10000	0	-0.79	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.007	0.062	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.06	0.086	-10000	0	-0.34	1	1
CaM/Ca2+	-0.073	0.16	-10000	0	-10000	0	0
RAP1A	0.029	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.084	0.15	-10000	0	-0.66	1	1
AKT1	-0.057	0.16	0.4	8	-10000	0	8
MAP2K1	-0.077	0.14	0.31	5	-10000	0	5
MAP3K11	-0.086	0.16	0.31	7	-0.58	1	8
IFNGR1	0.005	0.031	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.17	0.25	-10000	0	-0.59	98	98
Rap1/GTP	-0.073	0.11	-10000	0	-10000	0	0
CRKL/C3G	0.043	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.087	0.19	-10000	0	-10000	0	0
CEBPB	-0.007	0.15	0.5	11	-10000	0	11
STAT3	0.029	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.063	0.17	-10000	0	-0.62	3	3
STAT1	-0.083	0.16	0.32	8	-0.66	1	9
CALM1	0.028	0.008	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.24	0.3	-10000	0	-0.58	232	232
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
STAT1 (dimer)/PIAS1	-0.069	0.16	0.32	3	-0.62	1	4
CEBPB/PTGES2/Cbp/p300	-0.01	0.085	-10000	0	-0.4	1	1
mol:Ca2+	-0.081	0.16	-10000	0	-10000	0	0
MAPK3	-0.038	0.13	0.42	3	-0.62	1	4
STAT1 (dimer)	-0.075	0.12	-10000	0	-0.49	1	1
MAPK1	-0.037	0.13	0.45	4	-0.59	2	6
JAK2	0.005	0.031	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
JAK1	0.005	0.032	-10000	0	-10000	0	0
CAMK2D	0.03	0.004	-10000	0	-10000	0	0
DAPK1	0.008	0.13	0.4	18	-0.61	3	21
SMAD7	-0.011	0.077	0.24	20	-10000	0	20
CBL/CRKL/C3G	-0.061	0.16	-10000	0	-10000	0	0
PI3K	-0.07	0.15	-10000	0	-10000	0	0
IFNG	-0.24	0.3	-10000	0	-0.58	232	232
apoptosis	0	0.12	0.4	14	-0.43	7	21
CAMK2G	0.029	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.029	0.004	-10000	0	-10000	0	0
CAMK2A	-0.14	0.28	-10000	0	-0.64	127	127
CAMK2B	-0.063	0.22	-10000	0	-0.63	71	71
FRAP1	-0.057	0.14	0.35	12	-10000	0	12
PRKCD	-0.069	0.14	0.37	6	-10000	0	6
RAP1B	0.029	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	-0.06	0.086	-10000	0	-0.34	1	1
PTPN2	0.029	0.005	-10000	0	-10000	0	0
EP300	0.029	0.029	-10000	0	-0.63	1	1
IRF1	-0.036	0.12	0.42	5	-0.75	1	6
STAT1 (dimer)/PIASy	-0.071	0.16	0.37	2	-0.63	1	3
SOCS1	0.028	0.069	-10000	0	-0.98	1	1
mol:GDP	-0.061	0.15	-10000	0	-10000	0	0
CASP1	-0.012	0.076	0.24	20	-10000	0	20
PTGES2	0.026	0.041	-10000	0	-0.64	2	2
IRF9	0.023	0.071	0.25	17	-10000	0	17
mol:PI-3-4-5-P3	-0.077	0.14	-10000	0	-10000	0	0
RAP1/GDP	-0.061	0.12	-10000	0	-10000	0	0
CBL	-0.087	0.15	0.3	7	-10000	0	7
MAP3K1	-0.084	0.15	0.33	5	-10000	0	5
PIAS1	0.03	0.003	-10000	0	-10000	0	0
PIAS4	0.029	0.003	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.06	0.086	-10000	0	-0.34	1	1
PTPN11	-0.096	0.15	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.023	0.06	-10000	0	-10000	0	0
CRKL	0.03	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
DOCK1	0.028	0.03	-10000	0	-0.64	1	1
ITGA4	0.01	0.11	-10000	0	-0.59	16	16
alpha4/beta7 Integrin/MAdCAM1	0.031	0.092	-10000	0	-0.34	25	25
EPO	-0.17	0.29	-10000	0	-0.59	168	168
alpha4/beta7 Integrin	0.027	0.082	-10000	0	-0.43	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.027	0.082	-10000	0	-0.43	16	16
EPO/EPOR (dimer)	-0.11	0.22	-10000	0	-0.43	168	168
lamellipodium assembly	0.024	0.089	0.31	1	-0.54	6	7
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
PI3K	0.037	0.035	-10000	0	-0.47	2	2
ARF6	0.028	0.008	-10000	0	-10000	0	0
JAK2	-0.045	0.12	-10000	0	-0.39	10	10
PXN	0.029	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
MADCAM1	0.014	0.09	-10000	0	-0.6	11	11
cell adhesion	0.029	0.091	-10000	0	-0.34	25	25
CRKL/CBL	0.042	0.024	-10000	0	-0.47	1	1
ITGB1	0.029	0.004	-10000	0	-10000	0	0
SRC	0.014	0.084	-10000	0	-0.35	1	1
ITGB7	0.029	0.005	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.034	0.095	-10000	0	-0.37	26	26
p130Cas/Crk/Dock1	0.037	0.084	-10000	0	-0.59	1	1
VCAM1	0.015	0.089	-10000	0	-0.53	13	13
RHOA	0.021	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.058	0.073	-10000	0	-10000	0	0
BCAR1	0.008	0.082	-10000	0	-0.64	1	1
EPOR	0.03	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.028	0.029	-10000	0	-0.64	1	1
GIT1	0.029	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.023	0.091	0.32	1	-0.56	6	7

×

Canonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.013	-10000	0	-10000	0	0
AES	0.027	0.011	-10000	0	-10000	0	0
FBXW11	0.023	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.04	0.015	-10000	0	-10000	0	0
SMAD4	0.029	0.005	-10000	0	-10000	0	0
DKK2	0.001	0.13	-10000	0	-0.6	24	24
TLE1	0.027	0.012	-10000	0	-10000	0	0
MACF1	0.03	0.007	-10000	0	-10000	0	0
CTNNB1	0.037	0.12	0.41	10	-0.41	1	11
WIF1	0.002	0.066	-10000	0	-0.63	5	5
beta catenin/RanBP3	-0.009	0.089	0.32	10	-10000	0	10
KREMEN2	-0.043	0.2	-10000	0	-0.59	60	60
DKK1	0.002	0.13	-10000	0	-0.61	22	22
beta catenin/beta TrCP1	0.02	0.087	0.35	2	-10000	0	2
FZD1	0.027	0.01	-10000	0	-10000	0	0
AXIN2	-0.001	0.12	0.54	9	-1.4	2	11
AXIN1	0.029	0.007	-10000	0	-10000	0	0
RAN	0.029	0.006	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.005	0.12	-10000	0	-0.54	13	13
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.062	0.087	0.34	1	-0.75	1	2
Axin1/APC/GSK3	0.074	0.087	0.36	12	-10000	0	12
Axin1/APC/GSK3/beta catenin/Macf1	0.05	0.1	0.42	6	-10000	0	6
HNF1A	0.022	0.059	-10000	0	-0.64	4	4
CTBP1	0.027	0.012	-10000	0	-10000	0	0
MYC	-0.002	0.14	0.59	12	-0.53	3	15
RANBP3	0.03	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.009	0.15	-10000	0	-0.38	75	75
NKD1	-0.14	0.29	-10000	0	-0.63	134	134
TCF4	0.027	0.012	-10000	0	-10000	0	0
TCF3	0.027	0.011	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.046	0.088	-10000	0	-0.33	24	24
Ran/GTP	0.021	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.015	0.093	0.37	13	-0.52	2	15
LEF1	0.008	0.11	-10000	0	-0.6	16	16
DVL1	0.021	0.031	-10000	0	-0.3	2	2
CSNK2A1	0.03	0.006	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.07	0.088	0.35	1	-0.6	2	3
DKK1/LRP6/Kremen 2	-0.008	0.16	-10000	0	-0.4	69	69
LRP6	0.03	0.006	-10000	0	-10000	0	0
CSNK1A1	0.021	0.016	-10000	0	-10000	0	0
NLK	0.03	0.005	-10000	0	-10000	0	0
CCND1	-0.015	0.1	0.57	2	-0.48	17	19
WNT1	0	0.13	-10000	0	-0.59	25	25
GSK3A	0.031	0.004	-10000	0	-10000	0	0
GSK3B	0.028	0.008	-10000	0	-10000	0	0
FRAT1	0.028	0.006	-10000	0	-10000	0	0
PPP2R5D	0.098	0.14	0.34	124	-0.34	8	132
APC	0.027	0.096	0.38	9	-10000	0	9
WNT1/LRP6/FZD1	0.036	0.053	0.25	3	-10000	0	3
CREBBP	0.026	0.012	-10000	0	-10000	0	0

×

S1P5 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	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	0.007	0.095	0.57	1	-10000	0	1
GNAI2	0.021	0.014	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.032	0.15	-10000	0	-0.37	83	83
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
RhoA/GTP	-0.006	0.097	-10000	0	-0.58	1	1
negative regulation of cAMP metabolic process	-0.016	0.1	-10000	0	-0.36	19	19
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
GNAI3	0.029	0.006	-10000	0	-10000	0	0
GNA12	0.027	0.009	-10000	0	-10000	0	0
S1PR5	-0.079	0.24	-10000	0	-0.59	92	92
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.016	0.1	-10000	0	-0.36	19	19
RhoA/GDP	0.016	0.01	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
GNAI1	0.026	0.03	-10000	0	-0.64	1	1

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.032	0.09	-10000	0	-0.36	25	25
regulation of S phase of mitotic cell cycle	0.019	0.07	-10000	0	-0.38	6	6
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
HRAS	0.029	0.027	-10000	0	-0.59	1	1
SHBG/T-DHT	-0.024	0.13	-10000	0	-0.4	54	54
PELP1	0.029	0.006	-10000	0	-10000	0	0
AKT1	0.011	0.003	-10000	0	-10000	0	0
MAP2K1	0.009	0.073	0.35	1	-0.4	3	4
T-DHT/AR	-0.002	0.11	-10000	0	-0.46	26	26
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.009	13	13
GNAI2	0.021	0.014	-10000	0	-10000	0	0
GNAI3	0.029	0.006	-10000	0	-10000	0	0
GNAI1	0.026	0.03	-10000	0	-0.64	1	1
mol:GDP	-0.007	0.1	-10000	0	-0.46	24	24
cell proliferation	0.006	0.11	0.31	4	-0.56	6	10
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
FOS	0.01	0.14	-10000	0	-0.73	14	14
mol:Ca2+	0.003	0.016	-10000	0	-0.083	9	9
MAPK3	0.011	0.091	0.31	5	-0.48	5	10
MAPK1	0.014	0.062	-10000	0	-0.43	4	4
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:IP3	0	0.001	-10000	0	-0.005	12	12
cAMP biosynthetic process	-0.039	0.12	0.24	2	-0.39	53	55
GNG2	0.028	0.008	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	12	12
HRAS/GTP	0.041	0.08	-10000	0	-0.33	21	21
actin cytoskeleton reorganization	0.036	0.029	-10000	0	-0.32	2	2
SRC	0.029	0.006	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	12	12
PI3K	0.034	0.03	-10000	0	-0.41	2	2
apoptosis	-0.015	0.1	0.5	12	-0.26	3	15
T-DHT/AR/PELP1	0.019	0.094	-10000	0	-0.4	24	24
HRAS/GDP	0.01	0.1	-10000	0	-0.45	24	24
CREB1	0.016	0.11	0.27	2	-0.54	12	14
RAC1-CDC42/GTP	0.045	0.033	-10000	0	-0.32	2	2
AR	-0.002	0.14	-10000	0	-0.62	26	26
GNB1	0.029	0.006	-10000	0	-10000	0	0
RAF1	0.011	0.076	0.35	1	-0.39	3	4
RAC1-CDC42/GDP	0.03	0.1	-10000	0	-0.45	18	18
T-DHT/AR/PELP1/Src	0.038	0.085	-10000	0	-0.37	20	20
MAP2K2	0.008	0.072	0.35	1	-0.4	3	4
T-DHT/AR/PELP1/Src/PI3K	0.019	0.07	-10000	0	-0.38	6	6
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
SHBG	-0.039	0.2	-10000	0	-0.63	54	54
Gi family/GNB1/GNG2/GDP	-0.009	0.12	-10000	0	-0.5	15	15
mol:T-DHT	0	0.001	-10000	0	-0.007	9	9
RAC1	0.027	0.009	-10000	0	-10000	0	0
GNRH1	-0.12	0.2	-10000	0	-0.44	147	147
Gi family/GTP	0.007	0.059	-10000	0	-0.35	7	7
CDC42	0.029	0.006	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.053	0.06	-10000	0	-0.33	10	10
ER alpha/Gai/GDP/Gbeta gamma	-0.031	0.17	-10000	0	-0.54	36	36
AKT1	-0.03	0.22	-10000	0	-0.73	45	45
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.03	0.23	-10000	0	-0.75	45	45
mol:Ca2+	-0.018	0.12	-10000	0	-0.47	17	17
IGF1R	0.03	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.03	0.059	-10000	0	-0.45	7	7
SHC1	0.029	0.007	-10000	0	-10000	0	0
apoptosis	0.027	0.22	0.7	45	-10000	0	45
RhoA/GTP	0.017	0.034	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.004	0.14	-10000	0	-0.58	13	13
regulation of stress fiber formation	-0.034	0.058	0.48	1	-0.36	4	5
E2/ERA-ERB (dimer)	0.026	0.061	-10000	0	-0.39	10	10
KRAS	0.029	0.006	-10000	0	-10000	0	0
G13/GTP	0.031	0.037	-10000	0	-0.36	4	4
pseudopodium formation	0.034	0.058	0.36	4	-0.48	1	5
E2/ER alpha (dimer)/PELP1	0.033	0.04	-10000	0	-0.4	4	4
GRB2	0.029	0.005	-10000	0	-10000	0	0
GNG2	0.028	0.008	-10000	0	-10000	0	0
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
HRAS	0.029	0.027	-10000	0	-0.59	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.004	0.18	0.33	4	-0.54	40	44
E2/ER beta (dimer)	0.015	0.051	-10000	0	-0.41	7	7
mol:GDP	0.02	0.054	-10000	0	-0.42	4	4
mol:NADP	-0.004	0.18	0.33	4	-0.54	40	44
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:IP3	-0.019	0.13	-10000	0	-0.49	17	17
IGF-1R heterotetramer	0.03	0.003	-10000	0	-10000	0	0
PLCB1	0.015	0.09	-10000	0	-0.5	10	10
PLCB2	-0.014	0.12	-10000	0	-0.47	16	16
IGF1	0.023	0.06	-10000	0	-0.59	5	5
mol:L-citrulline	-0.004	0.18	0.33	4	-0.54	40	44
RHOA	0.021	0.014	-10000	0	-10000	0	0
Gai/GDP	-0.11	0.26	-10000	0	-0.53	119	119
JNK cascade	0.015	0.05	-10000	0	-0.41	7	7
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
ESR2	0.02	0.069	-10000	0	-0.56	7	7
GNAQ	0.029	0.006	-10000	0	-10000	0	0
ESR1	0.022	0.059	-10000	0	-0.56	5	5
Gq family/GDP/Gbeta gamma	0.021	0.12	-10000	0	-0.76	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.03	0.14	-10000	0	-0.91	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.005	0.14	-10000	0	-0.58	13	13
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
E2/ER alpha (dimer)	0.016	0.044	-10000	0	-0.42	5	5
STRN	0.024	0.058	-10000	0	-0.64	4	4
GNAL	0.029	0.005	-10000	0	-10000	0	0
PELP1	0.029	0.005	-10000	0	-10000	0	0
MAPK11	0.014	0.05	-10000	0	-0.38	8	8
GNAI2	0.021	0.014	-10000	0	-10000	0	0
GNAI3	0.029	0.006	-10000	0	-10000	0	0
GNAI1	0.026	0.03	-10000	0	-0.64	1	1
HBEGF	-0.08	0.18	0.41	10	-0.54	31	41
cAMP biosynthetic process	0.023	0.049	-10000	0	-0.31	10	10
SRC	-0.025	0.16	-10000	0	-0.62	21	21
PI3K	0.037	0.035	-10000	0	-0.47	2	2
GNB1	0.029	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.042	0.065	-10000	0	-0.4	2	2
SOS1	0.029	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.038	0.098	-10000	0	-0.48	13	13
Gs family/GTP	0.03	0.052	-10000	0	-0.32	10	10
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.053	0.023	-10000	0	-0.34	1	1
vasodilation	-0.002	0.17	0.31	5	-0.51	40	45
mol:DAG	-0.019	0.13	-10000	0	-0.49	17	17
Gs family/GDP/Gbeta gamma	0.021	0.056	-10000	0	-0.37	2	2
MSN	0.035	0.061	0.37	4	-0.52	1	5
Gq family/GTP	0.023	0.079	-10000	0	-0.48	9	9
mol:PI-3-4-5-P3	-0.028	0.22	-10000	0	-0.72	45	45
NRAS	0.029	0.006	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.002	0.17	0.51	40	-0.31	5	45
GRB2/SOS1	0.043	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.063	-10000	0	-0.41	3	3
NOS3	-0.006	0.19	0.36	3	-0.57	40	43
GNA11	0.026	0.05	-10000	0	-0.64	3	3
MAPKKK cascade	0.006	0.18	0.41	3	-0.55	44	47
E2/ER alpha (dimer)/PELP1/Src	0.002	0.15	-10000	0	-0.6	14	14
ruffle organization	0.034	0.058	0.36	4	-0.48	1	5
ROCK2	0.039	0.064	0.38	4	-0.58	1	5
GNA14	0.02	0.076	-10000	0	-0.64	7	7
GNA15	0.012	0.1	-10000	0	-0.59	15	15
GNA13	0.029	0.005	-10000	0	-10000	0	0
MMP9	-0.15	0.2	0.38	7	-0.5	63	70
MMP2	-0.019	0.16	0.33	2	-0.58	20	22

×

Regulation of Androgen receptor activity

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
HDAC1	0.022	0.006	-10000	0	-10000	0	0
SMARCC1	0.009	0.046	-10000	0	-0.66	2	2
REL	0.025	0.053	-10000	0	-0.56	4	4
HDAC7	-0.13	0.096	-10000	0	-0.61	4	4
JUN	0.029	0.006	-10000	0	-10000	0	0
EP300	0.028	0.029	-10000	0	-0.64	1	1
KAT2B	0.02	0.032	-10000	0	-0.64	1	1
KAT5	0.03	0.003	-10000	0	-10000	0	0
MAPK14	-0.016	0.041	-10000	0	-0.5	3	3
FOXO1	0.029	0.005	-10000	0	-10000	0	0
T-DHT/AR	-0.14	0.1	-10000	0	-0.6	5	5
MAP2K6	0.014	0.052	-10000	0	-0.66	3	3
BRM/BAF57	0.041	0.012	-10000	0	-10000	0	0
MAP2K4	0.018	0.011	-10000	0	-10000	0	0
SMARCA2	0.028	0.007	-10000	0	-10000	0	0
PDE9A	-0.12	0.14	-10000	0	-0.82	14	14
NCOA2	0.015	0.091	-10000	0	-0.64	10	10
CEBPA	0.018	0.085	-10000	0	-0.59	10	10
EHMT2	0.029	0.006	-10000	0	-10000	0	0
cell proliferation	-0.12	0.13	0.51	4	-0.47	16	20
NR0B1	-0.016	0.15	-10000	0	-0.59	32	32
EGR1	0.011	0.087	-10000	0	-0.64	9	9
RXRs/9cRA	0.048	0.037	-10000	0	-0.36	3	3
AR/RACK1/Src	-0.037	0.067	-10000	0	-0.46	5	5
AR/GR	-0.019	0.091	-10000	0	-0.5	11	11
GNB2L1	0.023	0.013	-10000	0	-10000	0	0
PKN1	0.03	0.002	-10000	0	-10000	0	0
RCHY1	0.03	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-0.017	1	1
MAPK8	-0.016	0.034	-10000	0	-0.48	2	2
T-DHT/AR/TIF2/CARM1	-0.048	0.093	-10000	0	-0.59	8	8
SRC	-0.037	0.042	-10000	0	-0.4	3	3
NR3C1	0.022	0.03	-10000	0	-0.59	1	1
KLK3	-0.027	0.14	0.35	1	-0.59	19	20
APPBP2	0	0.018	-10000	0	-10000	0	0
TRIM24	0.027	0.01	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.05	0.07	-10000	0	-0.49	6	6
TMPRSS2	-0.91	0.36	-10000	0	-1	460	460
RXRG	0.022	0.057	-10000	0	-0.62	4	4
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.029	0.005	-10000	0	-10000	0	0
RXRB	0.029	0.006	-10000	0	-10000	0	0
CARM1	0.03	0.003	-10000	0	-10000	0	0
NR2C2	0.02	0.032	-10000	0	-0.64	1	1
KLK2	-0.037	0.11	-10000	0	-0.54	16	16
AR	-0.023	0.077	-10000	0	-0.4	16	16
SENP1	0.029	0.005	-10000	0	-10000	0	0
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
MDM2	0.029	0.007	-10000	0	-10000	0	0
SRY	0	0.004	0.02	18	-10000	0	18
GATA2	0.014	0.096	-10000	0	-0.61	12	12
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.095	0.24	-10000	0	-0.59	101	101
T-DHT/AR/RACK1/Src	-0.037	0.067	-10000	0	-0.47	4	4
positive regulation of transcription	0.014	0.096	-10000	0	-0.61	12	12
DNAJA1	-0.001	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.009	-10000	0	-10000	0	0
NCOA1	0.054	0.032	-10000	0	-10000	0	0
SPDEF	-0.1	0.26	-10000	0	-0.6	111	111
T-DHT/AR/TIF2	-0.03	0.095	-10000	0	-0.54	9	9
T-DHT/AR/Hsp90	-0.048	0.068	-10000	0	-0.51	4	4
GSK3B	0.024	0.008	-10000	0	-10000	0	0
NR2C1	0.029	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.044	0.047	-10000	0	-0.41	5	5
SIRT1	0.029	0.005	-10000	0	-10000	0	0
ZMIZ2	0.027	0.01	-10000	0	-10000	0	0
POU2F1	-0.071	0.047	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.075	0.11	-10000	0	-0.55	11	11
CREBBP	0.029	0.006	-10000	0	-10000	0	0
SMARCE1	0.029	0.005	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.041	-10000	0	-0.64	2	2
SPHK1	-0.02	0.17	-10000	0	-0.59	42	42
GNAI2	0.021	0.014	-10000	0	-10000	0	0
mol:S1P	0.006	0.062	-10000	0	-0.31	3	3
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
mol:Sphinganine-1-P	-0.015	0.13	-10000	0	-0.44	43	43
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.048	0.061	-10000	0	-10000	0	0
GNAI3	0.029	0.006	-10000	0	-10000	0	0
G12/G13	0.039	0.015	-10000	0	-10000	0	0
S1PR3	0.029	0.006	-10000	0	-10000	0	0
S1PR2	0.03	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0	0.052	-10000	0	-0.27	3	3
S1PR5	-0.079	0.24	-10000	0	-0.59	92	92
S1PR4	-0.006	0.14	-10000	0	-0.59	30	30
GNAI1	0.026	0.03	-10000	0	-0.64	1	1
S1P/S1P5/G12	-0.025	0.15	-10000	0	-0.34	83	83
S1P/S1P3/Gq	0.022	0.09	-10000	0	-0.4	8	8
S1P/S1P4/Gi	0.013	0.076	0.29	1	-0.33	8	9
GNAQ	0.029	0.006	-10000	0	-10000	0	0
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
GNA14	0.02	0.076	-10000	0	-0.64	7	7
GNA15	0.012	0.1	-10000	0	-0.59	15	15
GNA12	0.027	0.009	-10000	0	-10000	0	0
GNA13	0.029	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.05	-10000	0	-0.64	3	3
ABCC1	0.029	0.006	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.008	0.11	-9999	-0.59	16	16
PLK4	0.026	0.047	-9999	-0.59	3	3
regulation of centriole replication	0.006	0.086	-9999	-0.43	19	19

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.002	0.11	-10000	0	-0.55	17	17
Crk/p130 Cas/Paxillin	-0.03	0.084	-10000	0	-0.42	5	5
JUN	0.006	0.095	-10000	0	-0.49	8	8
HRAS	0.029	0.027	-10000	0	-0.59	1	1
RET51/GFRalpha1/GDNF/GRB10	0.02	0.13	-10000	0	-0.39	38	38
RAP1A	0.029	0.006	-10000	0	-10000	0	0
FRS2	0.029	0.005	-10000	0	-10000	0	0
RAP1A/GDP	0.021	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.019	0.13	-10000	0	-0.4	38	38
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.029	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.01	0.1	-10000	0	-0.36	29	29
RHOA	0.021	0.014	-10000	0	-10000	0	0
RAP1A/GTP	0.02	0.12	-10000	0	-0.62	3	3
GRB7	0.02	0.076	-10000	0	-0.64	7	7
RET51/GFRalpha1/GDNF	0.02	0.14	-10000	0	-0.4	39	39
MAPKKK cascade	0.01	0.11	-10000	0	-0.53	4	4
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
RET9/GFRalpha1/GDNF/IRS1	0.012	0.11	-10000	0	-0.38	38	38
lamellipodium assembly	0.003	0.091	-10000	0	-0.37	6	6
RET51/GFRalpha1/GDNF/SHC	0.02	0.13	-10000	0	-0.39	41	41
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
RET9/GFRalpha1/GDNF/SHC	0.016	0.1	-10000	0	-0.37	33	33
RET9/GFRalpha1/GDNF/Shank3	0.016	0.11	-10000	0	-0.37	35	35
MAPK3	0.005	0.12	0.52	1	-0.59	3	4
DOK1	0.029	0.005	-10000	0	-10000	0	0
DOK6	0.016	0.092	-10000	0	-0.61	11	11
PXN	0.029	0.005	-10000	0	-10000	0	0
neurite development	0.005	0.11	-10000	0	-0.48	6	6
DOK5	0.016	0.09	-10000	0	-0.63	10	10
GFRA1	-0.016	0.16	-10000	0	-0.58	39	39
MAPK8	0.002	0.099	-10000	0	-0.5	9	9
HRAS/GTP	0.018	0.13	-10000	0	-0.6	4	4
tube development	0.02	0.1	-10000	0	-0.35	29	29
MAPK1	0.011	0.13	0.43	6	-0.59	3	9
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.009	0.074	-10000	0	-0.35	1	1
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
SRC	0.029	0.006	-10000	0	-10000	0	0
PDLIM7	0.019	0.048	-10000	0	-0.59	3	3
RET51/GFRalpha1/GDNF/Dok6	0.024	0.14	-10000	0	-0.62	9	9
SHC1	0.029	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.019	0.13	-10000	0	-0.4	39	39
RET51/GFRalpha1/GDNF/Dok5	0.014	0.15	-10000	0	-0.43	43	43
PRKCA	0.029	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.021	0.02	-10000	0	-0.44	1	1
CREB1	0.007	0.097	-10000	0	-0.44	9	9
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.006	0.082	-10000	0	-0.3	25	25
RET51/GFRalpha1/GDNF/Grb7	0.015	0.15	-10000	0	-0.43	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.007	0.12	-10000	0	-0.61	18	18
DOK4	0.029	0.006	-10000	0	-10000	0	0
JNK cascade	0.006	0.093	-10000	0	-0.48	8	8
RET9/GFRalpha1/GDNF/FRS2	0.017	0.1	-10000	0	-0.37	31	31
SHANK3	0.03	0.003	-10000	0	-10000	0	0
RASA1	0.025	0.03	-10000	0	-0.64	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.006	0.085	-10000	0	-0.3	31	31
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.005	0.095	-10000	0	-0.38	9	9
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.002	0.11	-10000	0	-0.42	16	16
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.004	0.1	-10000	0	-0.45	11	11
PI3K	0.005	0.14	-10000	0	-0.51	12	12
SOS1	0.029	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.028	0.1	-10000	0	-0.35	29	29
GRB10	0.027	0.009	-10000	0	-10000	0	0
activation of MAPKK activity	0.005	0.085	-10000	0	-0.41	3	3
RET51/GFRalpha1/GDNF/FRS2	0.021	0.13	-10000	0	-0.4	35	35
GAB1	0.03	0.004	-10000	0	-10000	0	0
IRS1	0.023	0.058	-10000	0	-0.64	4	4
IRS2	0.02	0.078	-10000	0	-0.6	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.002	0.11	-10000	0	-0.42	15	15
RET51/GFRalpha1/GDNF/PKC alpha	0.019	0.13	-10000	0	-0.4	38	38
GRB2	0.029	0.005	-10000	0	-10000	0	0
PRKACA	0.03	0.002	-10000	0	-10000	0	0
GDNF	0.017	0.047	-10000	0	-0.59	3	3
RAC1	0.027	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.015	0.14	-10000	0	-0.4	42	42
Rac1/GTP	0.01	0.11	-10000	0	-0.45	6	6
RET9/GFRalpha1/GDNF	-0.001	0.11	-10000	0	-0.41	35	35
GFRalpha1/GDNF	-0.003	0.13	-10000	0	-0.47	35	35

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.023	0.013	-9999	-10000	0	0
mol:S1P	0.001	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.011	0.049	-9999	-10000	0	0
GNAO1	0.026	0.055	-9999	-0.6	4	4
S1P/S1P3/G12/G13	0.051	0.022	-9999	-10000	0	0
AKT1	0.027	0.038	-9999	-0.37	1	1
AKT3	-0.017	0.097	-9999	-0.57	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.013	-9999	-10000	0	0
GNAI2	0.023	0.014	-9999	-10000	0	0
GNAI3	0.03	0.006	-9999	-10000	0	0
GNAI1	0.027	0.03	-9999	-0.63	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.031	0.006	-9999	-10000	0	0
S1PR2	0.03	0.003	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.033	0.04	-9999	-0.33	1	1
MAPK3	0.03	0.037	-9999	-10000	0	0
MAPK1	0.03	0.038	-9999	-10000	0	0
JAK2	-0.028	0.097	-9999	-0.46	4	4
CXCR4	-0.083	0.16	-9999	-0.41	7	7
FLT1	0.026	0.06	-9999	-0.59	5	5
RhoA/GDP	0.016	0.01	-9999	-10000	0	0
Rac1/GDP	0.02	0.007	-9999	-10000	0	0
SRC	0.03	0.037	-9999	-10000	0	0
S1P/S1P3/Gi	0.033	0.04	-9999	-0.34	1	1
RAC1	0.027	0.009	-9999	-10000	0	0
RhoA/GTP	0.038	0.047	-9999	-10000	0	0
VEGFA	-0.24	0.31	-9999	-0.59	234	234
S1P/S1P2/Gi	0.03	0.041	-9999	-0.34	1	1
VEGFR1 homodimer/VEGFA homodimer	-0.17	0.24	-9999	-0.44	234	234
RHOA	0.021	0.014	-9999	-10000	0	0
S1P/S1P3/Gq	0.027	0.058	-9999	-0.4	3	3
GNAQ	0.029	0.006	-9999	-10000	0	0
GNAZ	0.027	0.05	-9999	-0.63	3	3
G12/G13	0.039	0.015	-9999	-10000	0	0
GNA14	0.02	0.076	-9999	-0.64	7	7
GNA15	0.012	0.1	-9999	-0.59	15	15
GNA12	0.027	0.009	-9999	-10000	0	0
GNA13	0.029	0.005	-9999	-10000	0	0
GNA11	0.026	0.05	-9999	-0.64	3	3
Rac1/GTP	0.028	0.053	-9999	-10000	0	0

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.077	0.082	-10000	0	-0.38	1	1
epithelial cell differentiation	-0.049	0.1	-10000	0	-0.46	3	3
ITCH	0.063	0.02	-10000	0	-10000	0	0
WWP1	-0.092	0.064	-10000	0	-10000	0	0
FYN	0.028	0.008	-10000	0	-10000	0	0
EGFR	0.02	0.067	-10000	0	-0.6	6	6
PRL	0.021	0.007	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.047	0.08	0.38	2	-0.52	1	3
PTPRZ1	-0.049	0.2	-10000	0	-0.63	58	58
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.058	0.079	-10000	0	-0.44	5	5
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.08	0.083	-10000	0	-0.46	11	11
ADAM17	0.064	0.02	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.12	0.084	-10000	0	-0.33	3	3
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.11	0.092	-10000	0	-0.46	10	10
NCOR1	0.029	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.069	0.081	-10000	0	-0.45	9	9
GRIN2B	-0.067	0.077	-10000	0	-0.43	10	10
ErbB4/ErbB2/betacellulin	-0.12	0.14	-10000	0	-0.44	64	64
STAT1	0.027	0.028	-10000	0	-0.59	1	1
HBEGF	0.023	0.013	-10000	0	-10000	0	0
PRLR	-0.051	0.21	-10000	0	-0.64	62	62
E4ICDs/ETO2	-0.1	0.079	-10000	0	-0.45	3	3
axon guidance	-0.044	0.082	-10000	0	-10000	0	0
NEDD4	0.062	0.046	-10000	0	-0.62	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.027	0.16	-10000	0	-0.48	62	62
CBFA2T3	0.027	0.039	-10000	0	-0.59	2	2
ErbB4/ErbB2/HBEGF	-0.047	0.064	-10000	0	-0.44	1	1
MAPK3	-0.052	0.079	0.45	1	-0.54	1	2
STAT1 (dimer)	-0.1	0.076	-10000	0	-0.35	2	2
MAPK1	-0.051	0.081	0.38	2	-0.54	1	3
JAK2	0.028	0.007	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.076	0.079	-10000	0	-0.45	10	10
NRG1	0.026	0.082	-10000	0	-0.46	13	13
NRG3	0.016	0.09	-10000	0	-0.6	11	11
NRG2	0.012	0.081	-10000	0	-0.6	9	9
NRG4	-0.028	0.18	-10000	0	-0.63	45	45
heart development	-0.044	0.082	-10000	0	-10000	0	0
neural crest cell migration	-0.075	0.078	-10000	0	-0.45	10	10
ERBB2	0.042	0.034	-10000	0	-0.47	2	2
WWOX/E4ICDs	-0.1	0.077	-10000	0	-0.41	2	2
SHC1	0.029	0.007	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.12	0.13	-10000	0	-0.46	40	40
apoptosis	0.089	0.078	0.35	11	-10000	0	11
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.084	0.089	-10000	0	-0.39	9	9
ErbB4/ErbB2/epiregulin	-0.084	0.097	-10000	0	-0.41	22	22
ErbB4/ErbB4/betacellulin/betacellulin	-0.16	0.15	-10000	0	-0.48	78	78
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.094	0.13	-10000	0	-0.45	35	35
MDM2	-0.1	0.071	-10000	0	-0.38	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.052	0.071	-10000	0	-0.43	10	10
STAT5A	-0.038	0.077	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.072	0.086	-10000	0	-0.44	14	14
DLG4	0.029	0.005	-10000	0	-10000	0	0
GRB2/SHC	0.042	0.011	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.096	0.068	-10000	0	-0.35	1	1
STAT5A (dimer)	-0.048	0.12	-10000	0	-0.49	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.036	0.085	0.35	1	-10000	0	1
LRIG1	0.023	0.013	-10000	0	-10000	0	0
EREG	-0.009	0.15	-10000	0	-0.59	32	32
BTC	-0.069	0.24	-10000	0	-0.62	79	79
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.044	0.081	-10000	0	-10000	0	0
ERBB4	-0.12	0.084	-10000	0	-0.34	3	3
STAT5B	0.029	0.004	-10000	0	-10000	0	0
YAP1	-0.021	0.039	-10000	0	-0.53	2	2
GRB2	0.029	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.095	0.12	-10000	0	-0.44	37	37
glial cell differentiation	0.095	0.068	0.35	1	-10000	0	1
WWOX	0.027	0.028	-10000	0	-0.59	1	1
cell proliferation	-0.079	0.15	0.35	1	-0.54	20	21

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.008	0.026	-10000	0	-10000	0	0
RFC1	0.008	0.025	-10000	0	-10000	0	0
PRKDC	0.01	0.036	0.33	1	-10000	0	1
RIPK1	0.029	0.007	-10000	0	-10000	0	0
CASP7	-0.009	0.11	-10000	0	-0.64	11	11
FASLG/FAS/FADD/FAF1	-0.073	0.11	0.24	6	-0.31	2	8
MAP2K4	-0.053	0.15	0.31	5	-0.56	18	23
mol:ceramide	-0.084	0.13	-10000	0	-0.39	10	10
GSN	0.008	0.026	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.085	0.12	-10000	0	-0.44	4	4
FAS	0.027	0.011	-10000	0	-10000	0	0
BID	0.002	0.041	-10000	0	-10000	0	0
MAP3K1	-0.017	0.12	0.32	5	-0.51	15	20
MAP3K7	0.028	0.008	-10000	0	-10000	0	0
RB1	0.009	0.029	-10000	0	-10000	0	0
CFLAR	0.029	0.007	-10000	0	-10000	0	0
HGF/MET	0.03	0.1	-10000	0	-0.42	25	25
ARHGDIB	0.012	0.038	-10000	0	-10000	0	0
FADD	0.028	0.011	-10000	0	-10000	0	0
actin filament polymerization	-0.008	0.026	-10000	0	-10000	0	0
NFKB1	-0.027	0.088	-10000	0	-0.59	6	6
MAPK8	-0.061	0.17	0.41	3	-0.52	33	36
DFFA	0.008	0.025	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.008	0.025	-10000	0	-10000	0	0
FAS/FADD/MET	0.049	0.034	-10000	0	-0.37	2	2
CFLAR/RIP1	0.042	0.013	-10000	0	-10000	0	0
FAIM3	-0.013	0.16	-10000	0	-0.59	36	36
FAF1	0.026	0.014	-10000	0	-10000	0	0
PARP1	0.008	0.025	-10000	0	-10000	0	0
DFFB	0.008	0.025	-10000	0	-10000	0	0
CHUK	-0.021	0.078	-10000	0	-0.6	4	4
FASLG	-0.28	0.31	-10000	0	-0.59	258	258
FAS/FADD	0.04	0.017	-10000	0	-10000	0	0
HGF	0.003	0.12	-10000	0	-0.6	20	20
LMNA	0.007	0.033	0.29	1	-0.33	1	2
CASP6	0.008	0.025	-10000	0	-10000	0	0
CASP10	0.027	0.011	-10000	0	-10000	0	0
CASP3	0.006	0.032	-10000	0	-10000	0	0
PTPN13	0.018	0.086	-10000	0	-0.64	9	9
CASP8	0.005	0.07	0.26	36	-10000	0	36
IL6	-0.086	0.3	-10000	0	-1.1	32	32
MET	0.024	0.039	-10000	0	-0.59	2	2
ICAD/CAD	0.01	0.023	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.085	0.13	-10000	0	-0.39	10	10
activation of caspase activity by cytochrome c	0.002	0.041	-10000	0	-10000	0	0
PAK2	0.011	0.038	-10000	0	-10000	0	0
BCL2	0.029	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.037	0.051	-10000	0	-0.47	5	5
AKT1	-0.018	0.14	0.6	3	-0.63	2	5
PTK2B	-0.099	0.17	0.36	2	-0.89	1	3
VEGFR2 homodimer/Frs2	0.043	0.042	-10000	0	-0.76	1	1
CAV1	-0.009	0.14	-10000	0	-0.59	30	30
CALM1	0.028	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.11	0.19	-10000	0	-0.7	2	2
endothelial cell proliferation	0.002	0.16	0.49	18	-0.5	1	19
mol:Ca2+	-0.1	0.17	-10000	0	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.085	0.18	-10000	0	-0.8	1	1
RP11-342D11.1	-0.11	0.16	-10000	0	-0.89	1	1
CDH5	0.028	0.028	-10000	0	-0.59	1	1
VEGFA homodimer	-0.11	0.19	-10000	0	-0.33	146	146
SHC1	0.029	0.007	-10000	0	-10000	0	0
SHC2	0.022	0.068	-10000	0	-0.6	6	6
HRAS/GDP	-0.078	0.15	-10000	0	-0.6	2	2
SH2D2A	-0.16	0.29	-10000	0	-0.59	164	164
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.024	0.14	-10000	0	-0.6	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.22	0.23	-10000	0	-0.63	64	64
VEGFR1 homodimer	0.023	0.06	-10000	0	-0.59	5	5
SHC/GRB2/SOS1	-0.07	0.18	-10000	0	-0.73	1	1
GRB10	-0.095	0.16	-10000	0	-0.75	1	1
PTPN11	0.029	0.005	-10000	0	-10000	0	0
GRB2	0.029	0.005	-10000	0	-10000	0	0
PAK1	0.03	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.083	0.18	-10000	0	-0.75	2	2
HRAS	0.029	0.027	-10000	0	-0.59	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.05	0.11	-10000	0	-0.41	14	14
HIF1A	0.025	0.042	-10000	0	-0.64	2	2
FRS2	0.029	0.005	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.085	0.18	-10000	0	-0.79	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.022	0.013	-10000	0	-10000	0	0
Nck/Pak	0.041	0.025	-10000	0	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.11	0.19	-10000	0	-0.69	2	2
mol:GDP	-0.077	0.16	-10000	0	-0.7	1	1
mol:NADP	-0.02	0.13	0.47	5	-0.49	1	6
eNOS/Hsp90	-0.015	0.12	0.37	2	-0.45	1	3
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:IP3	-0.1	0.17	-10000	0	-0.76	1	1
HIF1A/ARNT	0.038	0.035	-10000	0	-0.47	2	2
SHB	0.029	0.006	-10000	0	-10000	0	0
VEGFA	-0.24	0.31	-10000	0	-0.59	234	234
VEGFC	0.028	0.027	-10000	0	-0.59	1	1
FAK1/Vinculin	-0.066	0.15	0.45	2	-0.68	2	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.091	0.19	-10000	0	-0.96	1	1
PTPN6	0.029	0.006	-10000	0	-10000	0	0
EPAS1	0.037	0.034	-10000	0	-0.48	2	2
mol:L-citrulline	-0.02	0.13	0.47	5	-0.49	1	6
ITGAV	0.029	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.09	0.19	-10000	0	-0.96	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.19	-10000	0	-0.99	1	1
VEGFR2/3 heterodimer	0.033	0.039	-10000	0	-0.49	2	2
VEGFB	0.03	0.003	-10000	0	-10000	0	0
MAPK11	-0.096	0.16	0.35	1	-0.66	2	3
VEGFR2 homodimer	0.032	0.045	-10000	0	-0.65	2	2
FLT1	0.023	0.06	-10000	0	-0.59	5	5
NEDD4	0.029	0.041	-10000	0	-0.63	2	2
MAPK3	-0.095	0.15	0.35	2	-0.72	1	3
MAPK1	-0.093	0.16	0.35	2	-0.66	1	3
VEGFA145/NRP2	-0.17	0.24	-10000	0	-0.43	231	231
VEGFR1/2 heterodimer	0.04	0.057	-10000	0	-0.74	1	1
KDR	0.032	0.045	-10000	0	-0.65	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.088	0.18	-10000	0	-0.88	2	2
SRC	0.029	0.006	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.084	0.17	0.46	4	-0.7	1	5
PI3K	-0.052	0.14	-10000	0	-0.58	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.11	0.19	-10000	0	-0.62	2	2
FES	-0.1	0.18	-10000	0	-0.78	2	2
GAB1	-0.059	0.14	-10000	0	-0.8	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.11	0.19	-10000	0	-0.62	2	2
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
SOS1	0.029	0.005	-10000	0	-10000	0	0
ARNT	0.029	0.007	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.033	0.12	0.33	1	-0.44	3	4
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.1	0.19	-10000	0	-0.7	2	2
PI3K/GAB1	-0.017	0.12	-10000	0	-0.49	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.079	0.18	-10000	0	-0.77	1	1
PRKACA	0.03	0.002	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.044	0.046	-10000	0	-0.55	1	1
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
CDC42	-0.1	0.17	-10000	0	-0.92	1	1
actin cytoskeleton reorganization	-0.22	0.23	-10000	0	-0.62	65	65
PTK2	-0.078	0.14	-10000	0	-0.74	2	2
EDG1	-0.11	0.16	-10000	0	-0.89	1	1
mol:DAG	-0.1	0.17	-10000	0	-0.76	1	1
CaM/Ca2+	-0.086	0.16	-10000	0	-0.69	1	1
MAP2K3	-0.098	0.16	0.39	1	-0.74	1	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.077	0.19	-10000	0	-0.79	1	1
PLCG1	-0.1	0.17	-10000	0	-0.78	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.091	0.19	-10000	0	-0.8	1	1
IQGAP1	0.03	0.004	-10000	0	-10000	0	0
YES1	0.029	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.11	0.19	-10000	0	-0.7	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.11	0.19	-10000	0	-0.7	2	2
cell migration	-0.033	0.14	0.43	3	-0.53	3	6
mol:PI-3-4-5-P3	-0.049	0.13	-10000	0	-0.53	3	3
FYN	0.028	0.008	-10000	0	-10000	0	0
VEGFB/NRP1	-0.093	0.16	-10000	0	-0.85	1	1
mol:NO	-0.02	0.13	0.47	5	-0.49	1	6
PXN	0.029	0.005	-10000	0	-10000	0	0
HRAS/GTP	-0.089	0.14	-10000	0	-0.6	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.091	0.17	-10000	0	-0.8	1	1
VHL	0.021	0.02	-10000	0	-0.32	1	1
ITGB3	0.023	0.065	-10000	0	-0.64	5	5
NOS3	-0.025	0.14	0.48	5	-0.56	1	6
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.2	-10000	0	-0.68	4	4
RAC1	0.027	0.009	-10000	0	-10000	0	0
PRKCA	-0.097	0.16	-10000	0	-0.71	1	1
PRKCB	-0.098	0.16	-10000	0	-0.64	2	2
VCL	0.029	0.006	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.1	0.18	-10000	0	-0.93	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.11	0.2	-10000	0	-0.65	6	6
VEGFA165/NRP2	-0.17	0.24	-10000	0	-0.43	231	231
MAPKKK cascade	-0.064	0.16	0.4	1	-0.53	2	3
NRP2	0.02	0.071	-10000	0	-0.59	7	7
VEGFC homodimer	0.028	0.027	-10000	0	-0.59	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
ROCK1	0.029	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	-0.065	0.15	0.45	2	-0.68	2	4
MAP3K13	-0.1	0.17	-10000	0	-0.78	1	1
PDPK1	-0.047	0.12	-10000	0	-0.63	2	2

×

TCGA08_rtk_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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.22	0.32	-10000	0	-0.63	202	202
HRAS	0.029	0.027	-10000	0	-0.59	1	1
EGFR	0.02	0.067	-10000	0	-0.6	6	6
AKT	0.032	0.088	0.32	12	-10000	0	12
FOXO3	0.028	0.008	-10000	0	-10000	0	0
AKT1	0.028	0.008	-10000	0	-10000	0	0
FOXO1	0.029	0.005	-10000	0	-10000	0	0
AKT3	0.028	0.007	-10000	0	-10000	0	0
FOXO4	0.03	0.001	-10000	0	-10000	0	0
MET	0.024	0.039	-10000	0	-0.59	2	2
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
PIK3CB	0.028	0.007	-10000	0	-10000	0	0
NRAS	0.029	0.006	-10000	0	-10000	0	0
PIK3CG	0.023	0.047	-10000	0	-0.59	3	3
PIK3R3	0.029	0.006	-10000	0	-10000	0	0
PIK3R2	0.03	0.003	-10000	0	-10000	0	0
NF1	0.029	0.004	-10000	0	-10000	0	0
RAS	-0.029	0.083	-10000	0	-0.26	4	4
ERBB2	0.027	0.041	-10000	0	-0.64	2	2
proliferation/survival/translation	-0.044	0.06	0.27	5	-0.23	1	6
PI3K	0	0.1	0.3	24	-0.28	4	28
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
KRAS	0.029	0.006	-10000	0	-10000	0	0
FOXO	0.057	0.071	0.27	23	-10000	0	23
AKT2	0.03	0.003	-10000	0	-10000	0	0
PTEN	0.029	0.006	-10000	0	-10000	0	0

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
CDC42/GTP	0.012	0.071	-10000	0	-0.33	5	5
PLCG1	0.012	0.06	-10000	0	-0.34	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.021	0.014	-10000	0	-10000	0	0
GNAI3	0.029	0.006	-10000	0	-10000	0	0
G12/G13	0.039	0.015	-10000	0	-10000	0	0
cell migration	0.011	0.069	-10000	0	-0.32	5	5
S1PR5	-0.079	0.24	-10000	0	-0.59	92	92
S1PR4	-0.006	0.14	-10000	0	-0.59	30	30
MAPK3	0.011	0.06	-10000	0	-0.34	5	5
MAPK1	0.012	0.061	-10000	0	-0.34	5	5
S1P/S1P5/Gi	-0.016	0.1	-10000	0	-0.36	19	19
GNAI1	0.026	0.03	-10000	0	-0.64	1	1
CDC42/GDP	0.021	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.032	0.15	-10000	0	-0.37	83	83
RHOA	0.012	0.091	0.36	4	-10000	0	4
S1P/S1P4/Gi	0.013	0.065	-10000	0	-0.36	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
S1P/S1P4/G12/G13	0.028	0.09	-10000	0	-0.34	28	28
GNA12	0.027	0.009	-10000	0	-10000	0	0
GNA13	0.029	0.005	-10000	0	-10000	0	0
CDC42	0.029	0.006	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.024	0.092	-9999	-0.42	19	19
E-cadherin/beta catenin	0.014	0.091	-9999	-0.47	17	17
CTNNB1	0.021	0.014	-9999	-10000	0	0
JUP	0.026	0.05	-9999	-0.64	3	3
CDH1	0.007	0.12	-9999	-0.62	18	18

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.03	0.003	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.044	0.092	-9999	-0.63	1	1
Syndecan-3/Neurocan	0.014	0.09	-9999	-0.33	32	32
POMC	0.026	0.044	-9999	-0.67	2	2
EGFR	0.02	0.067	-9999	-0.6	6	6
Syndecan-3/EGFR	0.018	0.079	-9999	-0.34	21	21
AGRP	0.022	0.041	-9999	-0.64	2	2
NCSTN	0.029	0.007	-9999	-10000	0	0
PSENEN	0.03	0.003	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.03	0.003	-9999	-10000	0	0
APH1A	0.029	0.007	-9999	-10000	0	0
NCAN	0.011	0.096	-9999	-0.59	13	13
long-term memory	0.04	0.073	-9999	-0.32	12	12
Syndecan-3/IL8	0.003	0.11	-9999	-0.32	51	51
PSEN1	0.028	0.008	-9999	-10000	0	0
Src/Cortactin	0.043	0.009	-9999	-10000	0	0
FYN	0.028	0.008	-9999	-10000	0	0
limb bud formation	0.012	0.056	-9999	-0.36	11	11
MC4R	0.01	0.08	-9999	-0.59	9	9
SRC	0.029	0.006	-9999	-10000	0	0
PTN	0.011	0.1	-9999	-0.63	13	13
FGFR/FGF/Syndecan-3	0.012	0.056	-9999	-0.36	11	11
neuron projection morphogenesis	0.023	0.1	-9999	-0.6	2	2
Syndecan-3/AgRP	0.019	0.075	-9999	-0.33	22	22
Syndecan-3/AgRP/MC4R	0.026	0.088	-9999	-0.33	16	16
Fyn/Cortactin	0.041	0.012	-9999	-10000	0	0
SDC3	0.011	0.057	-9999	-0.37	11	11
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.003	0.11	-9999	-0.31	51	51
IL8	-0.011	0.16	-9999	-0.6	34	34
Syndecan-3/Fyn/Cortactin	0.042	0.074	-9999	-0.33	12	12
Syndecan-3/CASK	0.004	0.069	-9999	-0.34	20	20
alpha-MSH/MC4R	0.026	0.07	-9999	-0.45	11	11
Gamma Secretase	0.079	0.029	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.029	0.004	-9999	-10000	0	0
ITGB7	0.029	0.005	-9999	-10000	0	0
ITGA4	0.01	0.11	-9999	-0.59	16	16
alpha4/beta7 Integrin	0.027	0.082	-9999	-0.43	16	16
alpha4/beta1 Integrin	0.027	0.082	-9999	-0.43	16	16

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.018	0.087	-10000	0	-0.56	3	3
BAG4	0.026	0.03	-10000	0	-0.64	1	1
BAD	0.02	0.056	0.38	5	-0.3	2	7
NFKBIA	0.028	0.007	-10000	0	-10000	0	0
BIRC3	-0.064	0.22	-10000	0	-0.59	79	79
BAX	0.022	0.048	0.25	11	-10000	0	11
EnzymeConsortium:3.1.4.12	0.011	0.032	0.12	12	-0.12	3	15
IKBKB	0.025	0.086	0.33	3	-0.52	3	6
MAP2K2	0.029	0.06	0.29	11	-0.28	1	12
MAP2K1	0.031	0.062	0.31	11	-10000	0	11
SMPD1	0.016	0.035	0.21	6	-0.15	2	8
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.026	0.092	0.37	1	-0.53	4	5
MAP2K4	0.037	0.072	0.26	25	-10000	0	25
protein ubiquitination	0.03	0.1	0.4	8	-0.54	3	11
EnzymeConsortium:2.7.1.37	0.036	0.07	0.36	10	-10000	0	10
response to UV	0	0.001	0.004	20	-0.003	1	21
RAF1	0.018	0.058	0.29	11	-0.25	3	14
CRADD	0.029	0.005	-10000	0	-10000	0	0
mol:ceramide	0.019	0.046	0.22	9	-0.18	3	12
I-kappa-B-alpha/RELA/p50/ubiquitin	0.038	0.01	-10000	0	-10000	0	0
MADD	0.03	0.003	-10000	0	-10000	0	0
MAP3K1	0.034	0.07	0.22	44	-10000	0	44
TRADD	0.029	0.006	-10000	0	-10000	0	0
RELA/p50	0.03	0.003	-10000	0	-10000	0	0
MAPK3	0.033	0.06	0.29	12	-10000	0	12
MAPK1	0.033	0.061	0.29	12	-10000	0	12
p50/RELA/I-kappa-B-alpha	0.042	0.011	-10000	0	-10000	0	0
FADD	0.015	0.087	0.37	1	-0.55	3	4
KSR1	0.022	0.056	0.26	10	-0.26	5	15
MAPK8	0.037	0.076	0.32	14	-0.28	2	16
TRAF2	0.029	0.006	-10000	0	-10000	0	0
response to radiation	0	0.001	0.004	8	-10000	0	8
CHUK	0.025	0.088	0.3	2	-0.52	3	5
TNF R/SODD	0.039	0.026	-10000	0	-0.47	1	1
TNF	0.019	0.079	-10000	0	-0.61	8	8
CYCS	0.026	0.06	0.25	15	-10000	0	15
IKBKG	0.026	0.091	0.32	3	-0.52	3	6
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.014	0.091	-10000	0	-0.51	5	5
RELA	0.03	0.003	-10000	0	-10000	0	0
RIPK1	0.029	0.006	-10000	0	-10000	0	0
AIFM1	0.02	0.052	0.26	11	-10000	0	11
TNF/TNF R/SODD	0.045	0.061	-10000	0	-0.39	9	9
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
response to heat	0	0.001	0.004	8	-10000	0	8
CASP8	0.024	0.097	-10000	0	-0.61	11	11
NSMAF	0.017	0.089	0.32	2	-0.55	3	5
response to hydrogen peroxide	0	0.001	0.004	20	-0.003	1	21
BCL2	0.029	0.005	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.029	0.082	-9999	-0.32	27	27
RGS9BP	0	0.14	-9999	-0.64	23	23
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.02	0.006	-9999	-10000	0	0
mol:Na +	0.021	0.052	-9999	-0.38	8	8
mol:ADP	0.004	0.031	-9999	-0.44	2	2
GNAT2	0.027	0.007	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.028	0.11	-9999	-0.39	34	34
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.031	0.01	-9999	-10000	0	0
GRK7	0.023	0.039	-9999	-0.59	2	2
CNGB3	0.014	0.068	-9999	-0.61	6	6
Cone Metarhodopsin II/X-Arrestin	0.016	0.004	-9999	-10000	0	0
mol:Ca2+	-0.013	0.077	-9999	-0.44	12	12
Cone PDE6	0.044	0.1	-9999	-0.36	6	6
Cone Metarhodopsin II	0.027	0.025	-9999	-0.35	2	2
Na + (4 Units)	0.025	0.075	-9999	-0.44	12	12
GNAT2/GDP	0.038	0.1	-9999	-0.35	25	25
GNB5	0.03	0.003	-9999	-10000	0	0
mol:GMP (4 units)	0.01	0.041	-9999	-0.33	2	2
Cone Transducin	0.032	0.088	-9999	-0.34	27	27
SLC24A2	0.011	0.074	-9999	-0.62	7	7
GNB3/GNGT2	0.017	0.1	-9999	-0.43	27	27
GNB3	-0.002	0.13	-9999	-0.59	26	26
GNAT2/GTP	0.02	0.005	-9999	-10000	0	0
CNGA3	0.017	0.046	-9999	-0.59	3	3
ARR3	0.021	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.021	0.052	-9999	-0.38	8	8
mol:Pi	0.027	0.11	-9999	-0.39	34	34
Cone CNG Channel	0.044	0.054	-9999	-0.45	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.011	0.074	-9999	-0.62	7	7
RGS9	0.013	0.1	-9999	-0.58	14	14
PDE6C	0.02	0.038	-9999	-0.59	2	2
GNGT2	0.028	0.027	-9999	-0.59	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.021	0.007	-9999	-10000	0	0

×

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

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
MET/RANBP9	0.036	0.033	-10000	0	-0.43	2	2
CRKL	0.049	0.097	0.39	8	-0.43	7	15
mol:PIP3	-0.011	0.044	-10000	0	-0.7	2	2
AKT1	0.001	0.056	-10000	0	-0.52	3	3
PTK2B	0.027	0.009	-10000	0	-10000	0	0
RAPGEF1	0.052	0.097	0.39	11	-0.48	3	14
RANBP10	0.029	0.006	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
HGF/MET/SHIP2	0.036	0.091	-10000	0	-0.4	20	20
MAP3K5	0.016	0.12	0.44	11	-0.49	3	14
HGF/MET/CIN85/CBL/ENDOPHILINS	0.05	0.092	-10000	0	-0.38	20	20
AP1	0.029	0.073	-10000	0	-0.4	12	12
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.029	0.007	-10000	0	-10000	0	0
apoptosis	-0.038	0.24	-10000	0	-0.71	55	55
STAT3 (dimer)	0.03	0.066	-10000	0	-0.48	3	3
GAB1/CRKL/SHP2/PI3K	0.066	0.086	0.43	1	-0.5	3	4
INPP5D	0.024	0.054	-10000	0	-0.59	4	4
CBL/CRK	0.064	0.098	0.35	11	-0.51	4	15
PTPN11	0.029	0.005	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.029	0.006	-10000	0	-10000	0	0
PTEN	0.029	0.006	-10000	0	-10000	0	0
ELK1	0.023	0.11	0.33	54	-0.24	2	56
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.024	0.043	-10000	0	-0.27	4	4
PAK1	0.004	0.056	0.38	1	-0.57	2	3
HGF/MET/RANBP10	0.035	0.089	-10000	0	-0.4	19	19
HRAS	0.019	0.099	-10000	0	-0.56	6	6
DOCK1	0.052	0.1	0.4	12	-0.51	4	16
GAB1	0.034	0.084	0.25	3	-0.46	7	10
CRK	0.047	0.093	0.31	9	-0.43	7	16
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.1	-10000	0	-0.56	10	10
JUN	0.029	0.006	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.009	0.042	-10000	0	-0.22	10	10
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
cell morphogenesis	0.082	0.14	0.49	29	-0.55	3	32
GRB2/SHC	0.039	0.045	-10000	0	-0.29	1	1
FOS	0.013	0.099	-10000	0	-0.63	12	12
GLMN	0.005	0.001	-10000	0	-10000	0	0
cell motility	0.022	0.11	0.33	54	-0.24	2	56
HGF/MET/MUC20	0.019	0.087	-10000	0	-0.4	20	20
cell migration	0.038	0.045	-10000	0	-0.29	1	1
GRB2	0.029	0.005	-10000	0	-10000	0	0
CBL	0.028	0.029	-10000	0	-0.64	1	1
MET/RANBP10	0.037	0.033	-10000	0	-0.43	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.023	0.061	-10000	0	-0.46	3	3
MET/MUC20	0.018	0.029	-10000	0	-0.44	2	2
RAP1B	0.06	0.11	0.52	12	-0.49	2	14
RAP1A	0.055	0.096	0.44	9	-0.58	1	10
HGF/MET/RANBP9	0.034	0.09	-10000	0	-0.4	20	20
RAF1	0.019	0.096	-10000	0	-0.57	4	4
STAT3	0.03	0.067	-10000	0	-0.48	3	3
cell proliferation	0.044	0.084	0.35	3	-0.48	3	6
RPS6KB1	0.013	0.037	-10000	0	-0.42	3	3
MAPK3	0.011	0.1	0.44	9	-10000	0	9
MAPK1	0.011	0.11	0.52	8	-10000	0	8
RANBP9	0.029	0.006	-10000	0	-10000	0	0
MAPK8	0.038	0.13	0.48	13	-0.46	5	18
SRC	0.02	0.057	-10000	0	-0.44	3	3
PI3K	0.037	0.055	-10000	0	-0.44	3	3
MET/Glomulin	0.018	0.033	-10000	0	-0.38	2	2
SOS1	0.029	0.005	-10000	0	-10000	0	0
MAP2K1	0.044	0.1	-10000	0	-0.55	3	3
MET	0.024	0.039	-10000	0	-0.59	2	2
MAP4K1	0.014	0.12	0.44	11	-0.48	5	16
PTK2	0.029	0.007	-10000	0	-10000	0	0
MAP2K2	0.045	0.1	0.42	2	-0.55	3	5
BAD	0.002	0.062	0.38	1	-0.6	3	4
MAP2K4	0.021	0.11	0.44	12	-0.54	1	13
SHP2/GRB2/SOS1/GAB1	0.045	0.067	-10000	0	-0.62	1	1
INPPL1	0.03	0.003	-10000	0	-10000	0	0
PXN	0.029	0.005	-10000	0	-10000	0	0
SH3KBP1	0.03	0.003	-10000	0	-10000	0	0
HGS	0.009	0.038	-10000	0	-0.31	1	1
PLCgamma1/PKC	0.021	0.004	-10000	0	-10000	0	0
HGF	0.003	0.12	-10000	0	-0.6	20	20
RASA1	0.025	0.03	-10000	0	-0.64	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
PTPRJ	0.03	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.04	0.054	-10000	0	-0.42	2	2
PDPK1	-0.002	0.058	-10000	0	-0.56	3	3
HGF/MET/SHIP	0.031	0.099	-10000	0	-0.41	23	23

×

Ephrin B reverse 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
EFNB2	0.029	0.004	-10000	0	-10000	0	0
EPHB2	0.019	0.076	-10000	0	-0.5	10	10
EFNB1	0.012	0.069	-10000	0	-0.44	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.052	0.082	-10000	0	-0.52	4	4
Ephrin B2/EPHB1-2	0.044	0.062	-10000	0	-0.42	7	7
neuron projection morphogenesis	0.033	0.073	-10000	0	-0.5	4	4
Ephrin B1/EPHB1-2/Tiam1	0.048	0.084	-10000	0	-0.56	4	4
DNM1	0.015	0.094	-10000	0	-0.6	12	12
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.003	0.087	-10000	0	-0.5	14	14
YES1	0.001	0.12	-10000	0	-0.74	14	14
Ephrin B1/EPHB1-2/NCK2	0.048	0.084	-10000	0	-0.56	4	4
PI3K	0.03	0.097	-10000	0	-0.53	13	13
mol:GDP	0.046	0.083	-10000	0	-0.55	4	4
ITGA2B	0.007	0.12	-10000	0	-0.59	19	19
endothelial cell proliferation	0.035	0.013	-10000	0	-10000	0	0
FYN	-0.001	0.13	-10000	0	-0.75	14	14
MAP3K7	-0.002	0.091	-10000	0	-0.56	13	13
FGR	0	0.12	-10000	0	-0.74	14	14
TIAM1	0.029	0.006	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
RGS3	0.029	0.006	-10000	0	-10000	0	0
cell adhesion	0.014	0.12	-10000	0	-0.6	11	11
LYN	0.001	0.12	-10000	0	-0.74	14	14
Ephrin B1/EPHB1-2/Src Family Kinases	-0.005	0.12	-10000	0	-0.69	14	14
Ephrin B1/EPHB1-2	-0.006	0.1	-10000	0	-0.6	14	14
SRC	0.003	0.12	-10000	0	-0.72	14	14
ITGB3	0.023	0.065	-10000	0	-0.64	5	5
EPHB1	0.023	0.056	-10000	0	-0.62	4	4
EPHB4	0.027	0.009	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.036	0.013	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.021	0.1	-10000	0	-0.46	23	23
BLK	-0.004	0.12	-10000	0	-0.74	14	14
HCK	-0.002	0.12	-10000	0	-0.73	14	14
regulation of stress fiber formation	-0.046	0.083	0.55	4	-10000	0	4
MAPK8	0.006	0.088	0.4	1	-0.5	12	13
Ephrin B1/EPHB1-2/RGS3	0.048	0.085	-10000	0	-0.56	4	4
endothelial cell migration	0.018	0.098	0.39	4	-0.5	10	14
NCK2	0.029	0.006	-10000	0	-10000	0	0
PTPN13	0.016	0.099	-10000	0	-0.73	9	9
regulation of focal adhesion formation	-0.046	0.083	0.55	4	-10000	0	4
chemotaxis	-0.047	0.083	0.55	4	-10000	0	4
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
Rac1/GTP	0.043	0.078	-10000	0	-0.52	4	4
angiogenesis	-0.006	0.099	-10000	0	-0.59	14	14
LCK	-0.002	0.13	-10000	0	-0.75	14	14

×

Signaling events mediated by PRL

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
CCNE1	0.022	0.071	-10000	0	-0.59	7	7
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	0.027	0.009	-10000	0	-10000	0	0
CDKN1A	0.018	0.049	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.026	0.085	-10000	0	-0.43	17	17
mol:Ca2+	-0.023	0.1	0.26	17	-0.44	21	38
AGT	0.001	0.13	-10000	0	-0.57	24	24
CCNA2	-0.044	0.13	-10000	0	-0.63	6	6
TUBA1B	0.029	0.005	-10000	0	-10000	0	0
EGR1	0.011	0.063	-10000	0	-0.46	9	9
CDK2/Cyclin E1	0.059	0.11	-10000	0	-0.55	5	5
MAPK3	0.007	0.081	-10000	0	-0.43	17	17
PRL-2 /Rab GGTase beta	0.043	0.009	-10000	0	-10000	0	0
MAPK1	0.008	0.081	-10000	0	-0.43	17	17
PTP4A1	0.01	0.046	-10000	0	-10000	0	0
PTP4A3	0.008	0.11	-10000	0	-0.59	17	17
PTP4A2	0.029	0.006	-10000	0	-10000	0	0
ITGB1	0.008	0.081	-10000	0	-0.43	17	17
SRC	0.029	0.006	-10000	0	-10000	0	0
RAC1	0.017	0.038	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.039	0.034	-10000	0	-0.47	2	2
PRL-1/ATF-5	0.062	0.087	-10000	0	-10000	0	0
RABGGTA	0.026	0.041	-10000	0	-0.64	2	2
BCAR1	-0.005	0.054	0.26	17	-0.49	1	18
RHOC	0.014	0.054	-10000	0	-0.58	1	1
RHOA	-0.026	0.12	-10000	0	-0.57	4	4
cell motility	0.021	0.09	0.29	8	-0.33	8	16
PRL-1/alpha Tubulin	0.063	0.082	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.024	0.083	-10000	0	-0.43	16	16
ROCK1	0.021	0.085	0.27	6	-0.32	6	12
RABGGTB	0.029	0.006	-10000	0	-10000	0	0
CDK2	0.029	0.005	-10000	0	-10000	0	0
mitosis	0.01	0.046	-10000	0	-10000	0	0
ATF5	0.026	0.047	-10000	0	-0.59	3	3

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.021	0.073	0.61	7	-10000	0	7
PI3K Class IB/PDE3B	0.021	0.073	-10000	0	-0.61	7	7
PDE3B	0.021	0.073	-10000	0	-0.61	7	7

×

Canonical NF-kappaB pathway

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
FBXW11	0.025	0.015	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.043	0.074	0.31	9	-10000	0	9
ERC1	0.029	0.006	-10000	0	-10000	0	0
RIP2/NOD2	-0.067	0.2	-10000	0	-0.44	116	116
NFKBIA	0.025	0.023	-10000	0	-10000	0	0
BIRC2	0.03	0.004	-10000	0	-10000	0	0
IKBKB	0.028	0.008	-10000	0	-10000	0	0
RIPK2	0.027	0.028	-10000	0	-0.59	1	1
IKBKG	0.009	0.067	-10000	0	-10000	0	0
IKK complex/A20	0.034	0.098	-10000	0	-0.48	1	1
NEMO/A20/RIP2	0.027	0.028	-10000	0	-0.59	1	1
XPO1	0.029	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.023	0.086	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.029	0.006	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.038	0.01	-10000	0	-10000	0	0
IKK complex/ELKS	0.026	0.077	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	0.057	0.015	-10000	0	-10000	0	0
NOD2	-0.11	0.26	-10000	0	-0.59	120	120
NFKB1	0.032	0.029	-10000	0	-0.63	1	1
RELA	0.034	0.003	-10000	0	-10000	0	0
MALT1	0.029	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.043	0.007	-10000	0	-10000	0	0
ATM	0.028	0.029	-10000	0	-0.64	1	1
TNF/TNFR1A	0.034	0.062	-10000	0	-0.45	8	8
TRAF6	0.03	0.003	-10000	0	-10000	0	0
PRKCA	0.029	0.005	-10000	0	-10000	0	0
CHUK	0.029	0.006	-10000	0	-10000	0	0
UBE2D3	0.03	0.004	-10000	0	-10000	0	0
TNF	0.019	0.079	-10000	0	-0.61	8	8
NF kappa B1 p50/RelA	0.053	0.037	-10000	0	-0.39	1	1
BCL10	0.029	0.006	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.023	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.025	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
IKK complex	0.032	0.087	-10000	0	-10000	0	0
CYLD	0.029	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.04	0.089	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.047	0.11	0.3	1	-0.57	7	8
CaM/Ca2+	0.021	0.006	-10000	0	-10000	0	0
AKT1	0.028	0.008	-10000	0	-10000	0	0
AKT2	0.03	0.003	-10000	0	-10000	0	0
STXBP4	0.029	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.042	0.13	0.27	34	-0.5	14	48
YWHAZ	0.028	0.007	-10000	0	-10000	0	0
CALM1	0.028	0.008	-10000	0	-10000	0	0
YWHAQ	0.029	0.005	-10000	0	-10000	0	0
TBC1D4	0.022	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.03	0.004	-10000	0	-10000	0	0
YWHAB	0.029	0.006	-10000	0	-10000	0	0
SNARE/Synip	0.057	0.016	-10000	0	-10000	0	0
YWHAG	0.027	0.009	-10000	0	-10000	0	0
ASIP	-0.027	0.17	-10000	0	-0.59	45	45
PRKCI	0.028	0.007	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.021	0.006	-10000	0	-10000	0	0
RHOQ	0.029	0.005	-10000	0	-10000	0	0
GYS1	0.023	0.009	-10000	0	-10000	0	0
PRKCZ	0.025	0.05	-10000	0	-0.64	3	3
TRIP10	0.03	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.039	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.021	0.062	-10000	0	-0.34	3	3
VAMP2	0.029	0.005	-10000	0	-10000	0	0
SLC2A4	0.04	0.14	0.33	9	-0.56	15	24
STX4	0.029	0.006	-10000	0	-10000	0	0
GSK3B	0.028	0.011	-10000	0	-10000	0	0
SFN	-0.041	0.2	-10000	0	-0.59	59	59
LNPEP	0.023	0.042	-10000	0	-0.64	2	2
YWHAE	0.029	0.005	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.029	0.006	-10000	0	-10000	0	0
mol:PIP3	0.007	0.046	-10000	0	-0.35	6	6
FRAP1	0.025	0.043	0.28	1	-10000	0	1
AKT1	0.023	0.065	0.28	2	-0.43	3	5
INSR	0.03	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.032	0.004	-10000	0	-10000	0	0
mol:GTP	0.045	0.062	0.3	1	-0.39	2	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.015	0.025	-10000	0	-0.26	1	1
TSC2	0.029	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.02	0.04	-10000	0	-0.36	2	2
TSC1	0.029	0.006	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.023	0.051	-10000	0	-0.37	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.029	0.033	-10000	0	-0.3	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.029	0.006	-10000	0	-10000	0	0
RPS6KB1	0.039	0.072	0.33	7	-0.55	1	8
MAP3K5	-0.004	0.051	0.17	1	-0.18	15	16
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
apoptosis	-0.004	0.051	0.17	1	-0.18	15	16
mol:LY294002	0	0	-10000	0	-0.001	14	14
EIF4B	0.044	0.077	0.33	14	-0.46	1	15
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.054	0.064	0.29	5	-0.61	1	6
eIF4E/eIF4G1/eIF4A1	0.02	0.018	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.034	0.057	-10000	0	-0.36	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.047	0.24	7	-0.22	1	8
FKBP1A	0.029	0.006	-10000	0	-10000	0	0
RHEB/GTP	0.041	0.053	-10000	0	-0.35	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	14	14
FKBP12/Rapamycin	0.022	0.005	-10000	0	-10000	0	0
PDPK1	0.007	0.05	-10000	0	-0.39	5	5
EIF4E	0.03	0.003	-10000	0	-10000	0	0
ASK1/PP5C	0.001	0.16	-10000	0	-0.54	41	41
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0.031	-10000	0	-10000	0	0
TSC1/TSC2	0.05	0.067	0.32	1	-0.42	2	3
tumor necrosis factor receptor activity	0	0	0.001	14	-10000	0	14
RPS6	0.026	0.039	-10000	0	-0.59	2	2
PPP5C	0.03	0.003	-10000	0	-10000	0	0
EIF4G1	0.029	0.006	-10000	0	-10000	0	0
IRS1	0.004	0.052	-10000	0	-0.23	22	22
INS	0.018	0.002	-10000	0	-10000	0	0
PTEN	0.028	0.006	-10000	0	-10000	0	0
PDK2	0.01	0.048	-10000	0	-0.38	2	2
EIF4EBP1	-0.064	0.28	-10000	0	-1	41	41
PIK3CA	0.028	0.03	-10000	0	-0.64	1	1
PPP2R5D	0.029	0.05	0.33	5	-10000	0	5
peptide biosynthetic process	0.018	0.013	-10000	0	-10000	0	0
RHEB	0.027	0.009	-10000	0	-10000	0	0
EIF4A1	0.029	0.005	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.001	0.005	17	-0.003	1	18
EEF2	0.018	0.013	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.044	0.26	-10000	0	-0.92	41	41

×

IL1-mediated signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.022	0.004	-10000	0	-10000	0	0
PRKCZ	0.025	0.05	-10000	0	-0.64	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.029	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.02	0.095	-10000	0	-0.39	2	2
IRAK/TOLLIP	0.038	0.009	-10000	0	-10000	0	0
IKBKB	0.028	0.008	-10000	0	-10000	0	0
IKBKG	0.03	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.024	0.17	-10000	0	-0.46	68	68
IL1A	0.011	0.1	-10000	0	-0.59	14	14
IL1B	0.017	0.049	-10000	0	-0.44	6	6
IRAK/TRAF6/p62/Atypical PKCs	0.055	0.045	-10000	0	-10000	0	0
IL1R2	-0.041	0.2	-10000	0	-0.61	58	58
IL1R1	0.029	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.009	0.046	-10000	0	-10000	0	0
TOLLIP	0.03	0.003	-10000	0	-10000	0	0
TICAM2	0.024	0.012	-10000	0	-10000	0	0
MAP3K3	0.029	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.019	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.058	0.06	-10000	0	-10000	0	0
JUN	0.02	0.044	0.33	2	-10000	0	2
MAP3K7	0.028	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.065	0.064	-10000	0	-0.65	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	0.039	0.078	-10000	0	-0.36	2	2
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.046	0.078	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	0.045	0.054	-10000	0	-0.34	9	9
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MAPK8	0.024	0.047	0.34	2	-10000	0	2
IRAK1	0.021	0.005	-10000	0	-10000	0	0
IL1RN/IL1R1	0.028	0.086	-10000	0	-0.44	17	17
IRAK4	0.029	0.005	-10000	0	-10000	0	0
PRKCI	0.028	0.007	-10000	0	-10000	0	0
TRAF6	0.03	0.003	-10000	0	-10000	0	0
PI3K	0.037	0.035	-10000	0	-0.47	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.077	-10000	0	-0.4	1	1
CHUK	0.029	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.045	0.054	-10000	0	-0.34	9	9
IL1 beta/IL1R2	-0.008	0.14	-10000	0	-0.39	61	61
IRAK/TRAF6/TAK1/TAB1/TAB2	0.043	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.049	0.063	-10000	0	-0.88	1	1
IRAK3	0.029	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.056	0.059	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.023	0.045	-10000	0	-0.35	1	1
IL1 alpha/IL1R1/IL1RAP	0.041	0.078	-10000	0	-0.37	17	17
RELA	0.03	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.022	0.013	-10000	0	-10000	0	0
MYD88	0.021	0.014	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.053	0.016	-10000	0	-10000	0	0
IL1RAP	0.024	0.055	-10000	0	-0.6	4	4
UBE2N	0.029	0.005	-10000	0	-10000	0	0
IRAK/TRAF6	0.03	0.043	-10000	0	-10000	0	0
CASP1	0.03	0.004	-10000	0	-10000	0	0
IL1RN/IL1R2	-0.026	0.18	-10000	0	-0.46	71	71
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.042	0.059	-10000	0	-10000	0	0
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.016	0.098	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
IL1RN	0.009	0.11	-10000	0	-0.6	17	17
TRAF6/TAK1/TAB1/TAB2	0.04	0.013	-10000	0	-10000	0	0
MAP2K6	0.029	0.043	0.35	2	-0.32	3	5

×

E-cadherin signaling in the nascent adherens junction

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.022	0.12	-10000	0	-0.48	17	17
KLHL20	0.022	0.075	0.21	2	-0.32	2	4
CYFIP2	0.014	0.077	-10000	0	-0.64	7	7
Rac1/GDP	0.024	0.087	0.3	4	-10000	0	4
ENAH	-0.02	0.12	-10000	0	-0.48	18	18
AP1M1	0.03	0.003	-10000	0	-10000	0	0
RAP1B	0.029	0.005	-10000	0	-10000	0	0
RAP1A	0.029	0.006	-10000	0	-10000	0	0
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
CDC42/GTP	0.028	0.053	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.013	0.034	-10000	0	-0.2	4	4
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.038	0.082	-10000	0	-0.37	14	14
RAPGEF1	-0.011	0.12	0.27	4	-0.43	12	16
CTNND1	0.03	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.023	0.13	-10000	0	-0.5	18	18
CRK	-0.01	0.12	-10000	0	-0.45	15	15
E-cadherin/gamma catenin/alpha catenin	0.028	0.089	-10000	0	-0.42	16	16
alphaE/beta7 Integrin	0.042	0.01	-10000	0	-10000	0	0
IQGAP1	0.03	0.004	-10000	0	-10000	0	0
NCKAP1	0.029	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.02	-10000	0	-10000	0	0
DLG1	-0.018	0.12	-10000	0	-0.48	16	16
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.029	-10000	0	-10000	0	0
MLLT4	0.027	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.05	0.025	-10000	0	-0.34	1	1
PI3K	-0.007	0.037	-10000	0	-10000	0	0
ARF6	0.028	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.022	0.1	-10000	0	-0.49	19	19
TIAM1	0.029	0.006	-10000	0	-10000	0	0
E-cadherin(dimer)/Ca2+	0.031	0.073	-10000	0	-0.34	14	14
AKT1	0.021	0.032	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
CDH1	0.007	0.12	-10000	0	-0.62	18	18
RhoA/GDP	0.041	0.085	0.34	9	-10000	0	9
actin cytoskeleton organization	0.023	0.062	0.17	15	-0.23	2	17
CDC42/GDP	0.032	0.11	0.37	15	-10000	0	15
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.011	0.063	-10000	0	-0.3	16	16
ITGB7	0.029	0.005	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.034	0.078	-10000	0	-0.36	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin	0.02	0.068	-10000	0	-0.34	14	14
mol:GDP	0.021	0.12	0.44	10	-0.4	3	13
CDC42/GTP/IQGAP1	0.039	0.009	-10000	0	-10000	0	0
JUP	0.026	0.05	-10000	0	-0.64	3	3
p120 catenin/RhoA/GDP	0.019	0.081	0.31	3	-10000	0	3
RAC1/GTP/IQGAP1	0.036	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.044	0.005	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
CDC42	0.029	0.006	-10000	0	-10000	0	0
CTNNA1	0.023	0.013	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.02	0.062	0.17	15	-0.22	18	33
NME1	0.028	0.027	-10000	0	-0.59	1	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.022	0.12	-10000	0	-0.48	17	17
regulation of cell-cell adhesion	0.013	0.042	-10000	0	-10000	0	0
WASF2	0.014	0.03	-10000	0	-10000	0	0
Rap1/GTP	0.034	0.066	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.05	0.087	-10000	0	-0.66	1	1
CCND1	0.021	0.073	0.2	8	-0.27	18	26
VAV2	-0.017	0.16	-10000	0	-0.56	16	16
RAP1/GDP	0.043	0.077	0.29	2	-10000	0	2
adherens junction assembly	-0.021	0.12	-10000	0	-0.47	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.029	0.004	-10000	0	-10000	0	0
PIP5K1C	0.03	0.003	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.048	0.091	-10000	0	-0.64	1	1
E-cadherin/beta catenin	0	0.078	-10000	0	-0.41	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.021	0.12	-10000	0	-0.48	17	17
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
Rac1/GTP	-0.031	0.078	-10000	0	-0.4	5	5
E-cadherin/beta catenin/alpha catenin	0.023	0.079	-10000	0	-0.4	14	14
ITGAE	0.029	0.005	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.024	0.13	-10000	0	-0.51	18	18

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.045	0.12	0.38	2	-0.55	10	12
MAP3K8	0.027	0.038	-10000	0	-0.59	2	2
FOS	0.032	0.1	0.36	4	-0.53	8	12
PRKCA	0.03	0.008	-10000	0	-10000	0	0
PTPN7	-0.01	0.15	-10000	0	-0.59	34	34
HRAS	0.029	0.027	-10000	0	-0.59	1	1
PRKCB	0.023	0.063	-10000	0	-0.62	5	5
NRAS	0.029	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.054	0.024	-10000	0	-0.34	1	1
MAPK3	0.019	0.087	-10000	0	-0.49	9	9
MAP2K1	0.029	0.054	-10000	0	-0.49	2	2
ELK1	0.03	0.009	-10000	0	-10000	0	0
BRAF	0.029	0.039	-10000	0	-0.45	2	2
mol:GTP	0	0.002	-10000	0	-0.007	13	13
MAPK1	0.019	0.088	-10000	0	-0.45	11	11
RAF1	0.022	0.04	-10000	0	-0.45	2	2
KRAS	0.029	0.006	-10000	0	-10000	0	0

×

ErbB2/ErbB3 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
USP8	0.011	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.015	0.094	-10000	0	-0.53	6	6
NFATC4	0.009	0.065	0.28	7	-0.48	1	8
ERBB2IP	0.027	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.028	0.008	-10000	0	-10000	0	0
mammary gland morphogenesis	0.014	0.073	-10000	0	-10000	0	0
JUN	0.019	0.065	0.27	3	-0.31	2	5
HRAS	0.028	0.027	-10000	0	-0.59	1	1
DOCK7	0.006	0.069	-10000	0	-0.57	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.027	0.083	-10000	0	-0.35	21	21
AKT1	0.011	0.005	-10000	0	-10000	0	0
BAD	0.01	0.025	-10000	0	-0.39	2	2
MAPK10	0.018	0.056	0.2	7	-0.31	2	9
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.015	0.078	-10000	0	-10000	0	0
RAF1	-0.006	0.087	-10000	0	-0.51	6	6
ErbB2/ErbB3/neuregulin 2	0.015	0.071	-10000	0	-0.36	16	16
STAT3	0.028	0.099	-10000	0	-0.89	6	6
cell migration	0.039	0.084	0.33	17	-0.26	2	19
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.11	0.19	-10000	0	-0.53	12	12
FOS	-0.068	0.14	0.3	1	-0.49	12	13
NRAS	0.028	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.073	-10000	0	-10000	0	0
MAPK3	-0.09	0.16	0.35	1	-0.56	6	7
MAPK1	-0.09	0.16	0.38	1	-0.58	7	8
JAK2	0.007	0.065	-10000	0	-10000	0	0
NF2	0.018	0.037	-10000	0	-0.79	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.009	0.085	-10000	0	-0.39	18	18
NRG1	0.008	0.11	-10000	0	-0.56	17	17
GRB2/SOS1	0.042	0.009	-10000	0	-10000	0	0
MAPK8	0.01	0.078	-10000	0	-0.37	6	6
MAPK9	0.011	0.044	0.2	5	-0.27	1	6
ERBB2	-0.015	0.03	-10000	0	-0.49	2	2
ERBB3	0.018	0.081	-10000	0	-0.64	8	8
SHC1	0.028	0.006	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
apoptosis	-0.006	0.022	0.28	2	-10000	0	2
STAT3 (dimer)	0.028	0.097	-10000	0	-0.87	6	6
RNF41	0.009	0.006	-10000	0	-10000	0	0
FRAP1	0.005	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.01	0.049	-10000	0	-0.39	1	1
ErbB2/ErbB2/HSP90 (dimer)	0.016	0.028	-10000	0	-0.42	2	2
CHRNA1	-0.12	0.19	0.34	1	-0.43	58	59
myelination	0.007	0.078	0.4	7	-0.43	1	8
PPP3CB	0.007	0.063	-10000	0	-10000	0	0
KRAS	0.028	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.034	0.085	-10000	0	-0.53	5	5
NRG2	0.012	0.081	-10000	0	-0.6	9	9
mol:GDP	0.009	0.085	-10000	0	-0.39	18	18
SOS1	0.029	0.005	-10000	0	-10000	0	0
MAP2K2	-0.015	0.091	0.29	1	-0.48	6	7
SRC	0.029	0.006	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.008	0.066	-10000	0	-10000	0	0
MAP2K1	-0.11	0.18	-10000	0	-0.56	14	14
heart morphogenesis	0.014	0.073	-10000	0	-10000	0	0
RAS family/GDP	0.041	0.091	-10000	0	-0.53	6	6
GRB2	0.029	0.005	-10000	0	-10000	0	0
PRKACA	0.016	0.038	-10000	0	-0.83	1	1
CHRNE	0.013	0.022	0.2	1	-0.19	2	3
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
activation of caspase activity	-0.011	0.005	-10000	0	-10000	0	0
nervous system development	0.014	0.073	-10000	0	-10000	0	0
CDC42	0.029	0.006	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.029	0.016	-10000	0	-0.32	1	1
ANTXR2	0.03	0.003	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0.002	0.002	-10000	0	-0.045	1	1
monocyte activation	0.004	0.092	-10000	0	-0.36	26	26
MAP2K2	0.014	0.06	-10000	0	-0.59	5	5
MAP2K1	0.004	0.002	-10000	0	-10000	0	0
MAP2K7	0.004	0.002	-10000	0	-10000	0	0
MAP2K6	0.002	0.026	-10000	0	-0.34	3	3
CYAA	0.006	0.007	-10000	0	-10000	0	0
MAP2K4	0.004	0.001	-10000	0	-10000	0	0
IL1B	0.006	0.045	0.24	6	-0.31	6	12
Channel	0.037	0.012	-10000	0	-10000	0	0
NLRP1	0.001	0.033	-10000	0	-0.34	5	5
CALM1	0.028	0.008	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.007	0.094	-10000	0	-0.37	33	33
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	-0.002	0.002	0.045	1	-10000	0	1
MAPK3	0.004	0.002	-10000	0	-10000	0	0
MAPK1	0.004	0.002	-10000	0	-10000	0	0
PGR	-0.007	0.061	-10000	0	-0.35	16	16
PA/Cellular Receptors	0.039	0.012	-10000	0	-10000	0	0
apoptosis	0.002	0.002	-10000	0	-0.045	1	1
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.036	0.011	-10000	0	-10000	0	0
macrophage activation	0.006	0.002	-10000	0	-10000	0	0
TNF	0.019	0.079	-10000	0	-0.61	8	8
VCAM1	0.004	0.092	-10000	0	-0.36	25	25
platelet activation	-0.007	0.094	-10000	0	-0.37	33	33
MAPKKK cascade	-0.01	0.018	-10000	0	-0.14	4	4
IL18	0.004	0.035	-10000	0	-0.31	5	5
negative regulation of macrophage activation	0.002	0.002	-10000	0	-0.045	1	1
LEF	0.002	0.002	-10000	0	-0.045	1	1
CASP1	0.005	0.017	-10000	0	-0.16	5	5
mol:cAMP	-0.007	0.095	-10000	0	-0.37	33	33
necrosis	0.002	0.002	-10000	0	-0.045	1	1
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.036	0.011	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.028	0.029	-10000	0	-0.64	1	1
HDAC4	0.028	0.007	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.018	0.027	0.41	2	-10000	0	2
CDKN1A	-0.004	0.025	-10000	0	-0.4	2	2
KAT2B	0.02	0.032	-10000	0	-0.64	1	1
BAX	0.03	0.003	-10000	0	-10000	0	0
FOXO3	-0.007	0.021	0.47	1	-10000	0	1
FOXO1	0.029	0.005	-10000	0	-10000	0	0
FOXO4	0.023	0.016	-10000	0	-0.3	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.03	0.004	-10000	0	-10000	0	0
TAT	0.015	0.085	-10000	0	-0.59	10	10
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.014	0.1	-10000	0	-0.43	30	30
PPARGC1A	-0.034	0.2	-10000	0	-0.63	51	51
FHL2	0.024	0.057	-10000	0	-0.62	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.039	0.01	-10000	0	-10000	0	0
HIST2H4A	0.018	0.027	-10000	0	-0.41	2	2
SIRT1/FOXO3a	0.01	0.027	0.31	1	-10000	0	1
SIRT1	0.024	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.051	0.019	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.034	0.03	-10000	0	-10000	0	0
apoptosis	-0.054	0.014	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.007	0.13	-10000	0	-0.41	50	50
p53/SIRT1	0.029	0.018	-10000	0	-10000	0	0
SIRT1/FOXO4	0.038	0.023	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.048	0.038	-10000	0	-0.36	4	4
HIST1H1E	0.022	0.019	-10000	0	-0.31	1	1
SIRT1/p300	0.038	0.025	-10000	0	-0.47	1	1
muscle cell differentiation	-0.003	0.093	0.37	30	-10000	0	30
TP53	0.024	0.008	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.054	0.014	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0
MEF2D	0.029	0.007	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.028	0.065	-10000	0	-0.43	10	10
ACSS2	0.02	0.006	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.003	0.093	-10000	0	-0.37	30	30

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.012	0.041	-10000	0	-0.4	5	5
SNTA1	0.028	0.03	-10000	0	-0.64	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.013	0.04	-10000	0	-0.39	5	5
MAPK12	0.004	0.05	-10000	0	-0.34	11	11
CCND1	0.008	0.045	-10000	0	-0.32	4	4
p38 gamma/SNTA1	0.026	0.062	-10000	0	-0.35	11	11
MAP2K3	0.029	0.005	-10000	0	-10000	0	0
PKN1	0.03	0.002	-10000	0	-10000	0	0
G2/M transition checkpoint	0.004	0.05	-10000	0	-0.34	11	11
MAP2K6	0.009	0.031	-10000	0	-0.4	3	3
MAPT	0.01	0.078	0.29	4	-0.39	15	19
MAPK13	0.018	0.048	-10000	0	-0.47	5	5
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.011	0.001	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0	0.23	-10000	0	-1.1	21	21
MKNK1	0.029	0.006	-10000	0	-10000	0	0
MAPK14	0.031	0.076	-10000	0	-0.42	2	2
ATF2/c-Jun	0.027	0.061	-10000	0	-0.43	1	1
MAPK11	0.029	0.086	-10000	0	-0.47	5	5
MITF	0.02	0.097	-10000	0	-0.54	6	6
MAPKAPK5	0.031	0.088	-10000	0	-0.5	3	3
KRT8	0.03	0.09	-10000	0	-0.49	4	4
MAPKAPK3	0.021	0.014	-10000	0	-10000	0	0
MAPKAPK2	0.029	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.038	0.12	-10000	0	-0.46	21	21
CEBPB	0.028	0.094	-10000	0	-0.5	3	3
SLC9A1	0.029	0.095	-10000	0	-0.58	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.034	0.091	-10000	0	-0.5	4	4
p38alpha-beta/MNK1	0.052	0.1	-10000	0	-0.55	3	3
JUN	0.029	0.062	-10000	0	-0.42	1	1
PPARGC1A	-0.005	0.14	-10000	0	-0.54	8	8
USF1	0.031	0.085	-10000	0	-0.45	2	2
RAB5/GDP/GDI1	0.021	0.066	-10000	0	-0.37	3	3
NOS2	0.031	0.1	-10000	0	-0.79	1	1
DDIT3	0.029	0.093	-10000	0	-0.48	5	5
RAB5A	0.022	0.014	-10000	0	-10000	0	0
HSPB1	0.043	0.11	0.3	42	-0.44	6	48
p38alpha-beta/HBP1	0.048	0.099	-10000	0	-0.56	3	3
CREB1	0.03	0.097	-10000	0	-0.54	6	6
RAB5/GDP	0.016	0.01	-10000	0	-10000	0	0
EIF4E	0.027	0.082	-10000	0	-0.53	2	2
RPS6KA4	0.032	0.089	-10000	0	-0.54	3	3
PLA2G4A	0.02	0.096	-10000	0	-0.56	5	5
GDI1	0.031	0.089	-10000	0	-0.5	3	3
TP53	0.021	0.11	-10000	0	-0.46	21	21
RPS6KA5	0.028	0.097	-10000	0	-0.56	6	6
ESR1	0.025	0.1	-10000	0	-0.58	6	6
HBP1	0.027	0.009	-10000	0	-10000	0	0
MEF2C	0.028	0.085	-10000	0	-0.5	4	4
MEF2A	0.032	0.091	-10000	0	-0.61	3	3
EIF4EBP1	0.024	0.11	-10000	0	-0.58	8	8
KRT19	-0.042	0.18	-10000	0	-0.67	14	14
ELK4	0.031	0.087	-10000	0	-0.48	3	3
ATF6	0.031	0.085	-10000	0	-0.45	2	2
ATF1	0.031	0.097	-10000	0	-0.54	6	6
p38alpha-beta/MAPKAPK2	0.053	0.1	-10000	0	-0.5	3	3
p38alpha-beta/MAPKAPK3	0.036	0.1	-10000	0	-0.56	3	3

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.008	0.12	-10000	0	-0.4	45	45
cell-cell adhesion	-0.003	0.052	0.55	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	0.064	0.069	-10000	0	-10000	0	0
ITSN1	0.029	0.006	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
SHC1	0.029	0.007	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.029	0.064	-10000	0	-0.41	11	11
Ephrin B1/EPHB1	0.035	0.038	-10000	0	-0.39	4	4
HRAS/GDP	0.034	0.059	-10000	0	-0.48	1	1
Ephrin B/EPHB1/GRB7	0.068	0.076	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.022	0.055	-10000	0	-10000	0	0
KRAS	0.029	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.071	0.064	-10000	0	-10000	0	0
endothelial cell migration	0.05	0.036	-10000	0	-0.34	2	2
GRB2	0.029	0.005	-10000	0	-10000	0	0
GRB7	0.02	0.076	-10000	0	-0.64	7	7
PAK1	0.028	0.055	-10000	0	-10000	0	0
HRAS	0.029	0.027	-10000	0	-0.59	1	1
RRAS	0.023	0.055	-10000	0	-10000	0	0
DNM1	0.015	0.094	-10000	0	-0.6	12	12
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.026	0.054	-10000	0	-10000	0	0
lamellipodium assembly	0.003	0.052	-10000	0	-0.55	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.038	0.046	-10000	0	-0.43	1	1
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
EPHB2	0.019	0.076	-10000	0	-0.5	10	10
EPHB3	0.015	0.095	-10000	0	-0.64	11	11
EPHB1	0.023	0.056	-10000	0	-0.61	4	4
EPHB4	0.027	0.009	-10000	0	-10000	0	0
mol:GDP	0.022	0.057	0.34	3	-0.47	1	4
Ephrin B/EPHB2	0.058	0.06	-10000	0	-10000	0	0
Ephrin B/EPHB3	0.052	0.078	-10000	0	-0.37	16	16
JNK cascade	0.025	0.066	0.36	5	-0.56	2	7
Ephrin B/EPHB1	0.057	0.059	-10000	0	-0.35	7	7
RAP1/GDP	0.064	0.078	0.35	5	-10000	0	5
EFNB2	0.029	0.004	-10000	0	-10000	0	0
EFNB3	0.021	0.072	-10000	0	-0.59	7	7
EFNB1	0.03	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.044	0.062	-10000	0	-0.42	7	7
RAP1B	0.029	0.005	-10000	0	-10000	0	0
RAP1A	0.029	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.045	0.073	-10000	0	-0.54	2	2
Rap1/GTP	0.022	0.058	-10000	0	-0.56	1	1
axon guidance	-0.008	0.12	-10000	0	-0.4	45	45
MAPK3	0.032	0.043	-10000	0	-0.38	1	1
MAPK1	0.033	0.043	-10000	0	-0.38	1	1
Rac1/GDP	0.038	0.063	0.36	2	-0.43	1	3
actin cytoskeleton reorganization	-0.008	0.044	-10000	0	-0.39	3	3
CDC42/GDP	0.057	0.081	0.35	6	-0.42	1	7
PI3K	0.056	0.038	-10000	0	-0.35	2	2
EFNA5	-0.026	0.18	-10000	0	-0.63	40	40
Ephrin B2/EPHB4	0.036	0.013	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.032	0.05	-10000	0	-0.37	1	1
CDC42	0.029	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.016	0.059	-10000	0	-0.54	2	2
PTK2	0.021	0.085	0.53	14	-10000	0	14
MAP4K4	0.025	0.066	0.36	5	-0.57	2	7
SRC	0.029	0.006	-10000	0	-10000	0	0
KALRN	0.028	0.008	-10000	0	-10000	0	0
Intersectin/N-WASP	0.039	0.015	-10000	0	-10000	0	0
neuron projection morphogenesis	0.073	0.12	0.42	36	-0.45	1	37
MAP2K1	0.034	0.043	-10000	0	-0.4	1	1
WASL	0.027	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.06	0.069	-10000	0	-0.47	5	5
cell migration	0.047	0.079	0.46	5	-0.43	1	6
NRAS	0.029	0.006	-10000	0	-10000	0	0
SYNJ1	0.022	0.056	-10000	0	-10000	0	0
PXN	0.029	0.005	-10000	0	-10000	0	0
TF	-0.054	0.14	-10000	0	-0.6	2	2
HRAS/GTP	0.044	0.072	-10000	0	-0.59	2	2
Ephrin B1/EPHB1-2	0.044	0.064	-10000	0	-0.41	8	8
cell adhesion mediated by integrin	-0.005	0.058	0.37	6	-0.37	3	9
RAC1	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0.048	0.073	-10000	0	-0.54	2	2
RAC1-CDC42/GTP	0.004	0.071	-10000	0	-0.68	2	2
RASA1	0.025	0.03	-10000	0	-0.64	1	1
RAC1-CDC42/GDP	0.05	0.063	0.36	2	-10000	0	2
ruffle organization	0.073	0.13	0.4	48	-0.56	1	49
NCK1	0.027	0.03	-10000	0	-0.64	1	1
receptor internalization	0.01	0.069	-10000	0	-0.42	1	1
Ephrin B/EPHB2/KALRN	0.069	0.066	-10000	0	-10000	0	0
ROCK1	0.02	0.061	-10000	0	-0.37	11	11
RAS family/GDP	-0.008	0.044	-10000	0	-0.42	1	1
Rac1/GTP	0.011	0.057	-10000	0	-0.59	1	1
Ephrin B/EPHB1/Src/Paxillin	0.035	0.043	-10000	0	-0.34	1	1

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.012	0.083	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SLAP	0.009	0.1	-10000	0	-0.44	25	25
PDGFB-D/PDGFRB/APS/CBL	0.04	0.047	-10000	0	-0.38	4	4
AKT1	0.087	0.13	0.38	58	-10000	0	58
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.041	0.1	0.34	6	-10000	0	6
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
FGR	0.037	0.1	0.33	6	-0.62	2	8
mol:Ca2+	0.049	0.065	0.33	8	-10000	0	8
MYC	0.062	0.14	0.47	17	-0.44	4	21
SHC1	0.029	0.007	-10000	0	-10000	0	0
HRAS/GDP	0.051	0.055	-10000	0	-0.63	1	1
LRP1/PDGFRB/PDGFB	0.046	0.027	-10000	0	-10000	0	0
GRB10	0.027	0.009	-10000	0	-10000	0	0
PTPN11	0.029	0.005	-10000	0	-10000	0	0
GO:0007205	0.049	0.065	0.34	7	-10000	0	7
PTEN	0.029	0.006	-10000	0	-10000	0	0
GRB2	0.029	0.005	-10000	0	-10000	0	0
GRB7	0.02	0.076	-10000	0	-0.64	7	7
PDGFB-D/PDGFRB/SHP2	0.033	0.02	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.032	0.02	-10000	0	-10000	0	0
cell cycle arrest	0.009	0.1	-10000	0	-0.44	25	25
HRAS	0.029	0.027	-10000	0	-0.59	1	1
HIF1A	0.079	0.13	0.37	57	-0.53	1	58
GAB1	0.046	0.083	0.35	8	-10000	0	8
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.046	0.087	0.38	8	-10000	0	8
PDGFB-D/PDGFRB	0.044	0.029	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.033	0.02	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.009	0.085	-10000	0	-0.4	1	1
positive regulation of MAPKKK cascade	0.033	0.02	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
mol:IP3	0.049	0.066	0.34	7	-10000	0	7
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.028	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.027	0.059	-10000	0	-0.48	6	6
SHB	0.029	0.006	-10000	0	-10000	0	0
BLK	0.013	0.12	0.32	4	-0.48	8	12
PTPN2	0.031	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.034	0.019	-10000	0	-10000	0	0
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
VAV2	0.048	0.092	0.38	8	-10000	0	8
CBL	0.028	0.029	-10000	0	-0.64	1	1
PDGFB-D/PDGFRB/DEP1	0.034	0.019	-10000	0	-10000	0	0
LCK	0.029	0.12	0.33	6	-0.57	4	10
PDGFRB	0.023	0.013	-10000	0	-10000	0	0
ACP1	0.029	0.005	-10000	0	-10000	0	0
HCK	0.043	0.082	0.34	5	-10000	0	5
ABL1	0.048	0.089	0.34	11	-0.44	2	13
PDGFB-D/PDGFRB/CBL	0.041	0.076	0.38	2	-10000	0	2
PTPN1	0.03	0.007	-10000	0	-10000	0	0
SNX15	0.03	0.003	-10000	0	-10000	0	0
STAT3	0.029	0.004	-10000	0	-10000	0	0
STAT1	0.027	0.028	-10000	0	-0.59	1	1
cell proliferation	0.062	0.13	0.44	19	-0.4	4	23
SLA	-0.002	0.13	-10000	0	-0.59	26	26
actin cytoskeleton reorganization	0.041	0.047	0.36	2	-10000	0	2
SRC	0.05	0.064	0.32	4	-10000	0	4
PI3K	0.011	0.025	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.039	0.054	-10000	0	-0.41	5	5
SH2B2	0.022	0.054	-10000	0	-0.59	4	4
PLCgamma1/SPHK1	0.042	0.1	0.34	6	-10000	0	6
LYN	0.041	0.09	0.32	3	-0.63	2	5
LRP1	0.029	0.005	-10000	0	-10000	0	0
SOS1	0.029	0.005	-10000	0	-10000	0	0
STAT5B	0.029	0.004	-10000	0	-10000	0	0
STAT5A	0.029	0.004	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.061	0.05	-10000	0	-10000	0	0
SPHK1	-0.019	0.17	-10000	0	-0.59	42	42
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.049	0.066	0.34	7	-10000	0	7
PLCG1	0.05	0.066	0.34	7	-10000	0	7
NHERF/PDGFRB	0.044	0.034	-10000	0	-0.4	1	1
YES1	0.048	0.073	0.32	2	-0.55	2	4
cell migration	0.043	0.033	-10000	0	-0.4	1	1
SHC/Grb2/SOS1	0.063	0.043	-10000	0	-10000	0	0
SLC9A3R2	0.027	0.03	-10000	0	-0.64	1	1
SLC9A3R1	0.029	0.005	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.054	0.04	-10000	0	-0.37	1	1
FYN	0.029	0.11	0.32	4	-0.45	6	10
DOK1	0.06	0.063	-10000	0	-10000	0	0
HRAS/GTP	0.021	0.02	-10000	0	-0.44	1	1
PDGFB	0.03	0.004	-10000	0	-10000	0	0
RAC1	0.065	0.12	0.46	13	-0.48	1	14
PRKCD	0.039	0.057	-10000	0	-0.34	1	1
FER	0.035	0.051	-10000	0	-0.38	2	2
MAPKKK cascade	0.043	0.082	0.37	15	-10000	0	15
RASA1	0.045	0.057	-10000	0	-0.38	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
NCK2	0.029	0.006	-10000	0	-10000	0	0
p62DOK/Csk	0.075	0.059	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.033	0.02	-10000	0	-10000	0	0
chemotaxis	0.048	0.088	0.34	11	-0.43	2	13
STAT1-3-5/STAT1-3-5	0.052	0.038	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.017	0.01	-10000	0	-10000	0	0
PTPRJ	0.03	0.003	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.024	0.008	-10000	0	-10000	0	0
TRAF2/ASK1	0.036	0.012	-10000	0	-10000	0	0
ATM	0.028	0.029	-10000	0	-0.64	1	1
MAP2K3	0.034	0.069	0.47	3	-10000	0	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.036	0.071	0.41	3	-0.36	3	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.018	0.081	-10000	0	-0.6	9	9
TXN	0.01	0.002	-10000	0	-10000	0	0
CALM1	0.028	0.008	-10000	0	-10000	0	0
GADD45A	0.029	0.006	-10000	0	-10000	0	0
GADD45B	0.03	0.003	-10000	0	-10000	0	0
MAP3K1	0.027	0.009	-10000	0	-10000	0	0
MAP3K6	0.028	0.03	-10000	0	-0.64	1	1
MAP3K7	0.028	0.007	-10000	0	-10000	0	0
MAP3K4	0.028	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.039	0.026	-10000	0	-0.47	1	1
TAK1/TAB family	-0.003	0.015	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.05	0.019	-10000	0	-10000	0	0
TRAF2	0.029	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.039	0.051	-10000	0	-10000	0	0
TRAF6	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.063	0.22	-10000	0	-0.63	71	71
CCM2	0.027	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.025	0.15	-10000	0	-0.4	71	71
MAPK11	0.027	0.038	-10000	0	-0.59	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.009	0.14	-10000	0	-0.36	71	71
OSM/MEKK3	0.039	0.015	-10000	0	-10000	0	0
TAOK1	0.015	0.045	-10000	0	-0.34	8	8
TAOK2	0.02	0.018	-10000	0	-0.37	1	1
TAOK3	0.02	0.017	-10000	0	-0.37	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.029	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.028	0.008	-10000	0	-10000	0	0
MAP3K10	0.028	0.029	-10000	0	-0.64	1	1
MAP3K3	0.029	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.025	0.018	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.057	0.052	-10000	0	-0.3	6	6

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.038	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.029	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.05	-10000	0	-0.64	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.029	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.021	0.029	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.029	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.029	0.005	-10000	0	-10000	0	0
FYN	0.028	0.008	-10000	0	-10000	0	0
MAP3K12	0.028	0.029	-10000	0	-0.64	1	1
FGR	0.025	0.047	-10000	0	-0.59	3	3
p38 alpha/TAB1	-0.022	0.08	-10000	0	-0.61	7	7
PRKG1	0.011	0.11	-10000	0	-0.64	14	14
DUSP8	0.029	0.029	-10000	0	-0.64	1	1
PGK/cGMP/p38 alpha	0.023	0.11	-10000	0	-0.5	11	11
apoptosis	-0.021	0.076	-10000	0	-0.57	7	7
RAL/GTP	0.035	0.014	-10000	0	-10000	0	0
LYN	0.028	0.007	-10000	0	-10000	0	0
DUSP1	0.021	0.03	-10000	0	-0.59	1	1
PAK1	0.03	0.003	-10000	0	-10000	0	0
SRC	0.029	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.067	0.026	-10000	0	-10000	0	0
TRAF6	0.03	0.003	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.027	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.035	0.014	-10000	0	-10000	0	0
MAPK11	0.045	0.12	0.38	13	-0.43	8	21
BLK	-0.013	0.15	-10000	0	-0.59	34	34
HCK	-0.003	0.14	-10000	0	-0.59	27	27
MAP2K3	0.029	0.005	-10000	0	-10000	0	0
DUSP16	0.029	0.006	-10000	0	-10000	0	0
DUSP10	0.025	0.05	-10000	0	-0.63	3	3
TRAF6/MEKK3	0.037	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.04	0.12	0.31	13	-0.66	7	20
positive regulation of innate immune response	0.051	0.14	0.41	13	-0.59	8	21
LCK	0.003	0.12	-10000	0	-0.59	22	22
p38alpha-beta/MKP7	0.055	0.12	0.36	6	-0.62	6	12
p38alpha-beta/MKP5	0.058	0.14	0.45	9	-0.58	8	17
PGK/cGMP	0.008	0.08	-10000	0	-0.47	14	14
PAK2	0.028	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.035	0.12	0.43	4	-0.58	7	11
CDC42	0.029	0.006	-10000	0	-10000	0	0
RALB	0.029	0.005	-10000	0	-10000	0	0
RALA	0.027	0.009	-10000	0	-10000	0	0
PAK3	0.013	0.098	-10000	0	-0.6	13	13

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.044	0.056	-10000	0	-10000	0	0
TC10/GTP	0.044	0.043	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.064	0.045	-10000	0	-0.38	4	4
HRAS	0.029	0.027	-10000	0	-0.59	1	1
APS homodimer	0.022	0.054	-10000	0	-0.59	4	4
GRB14	-0.005	0.15	-10000	0	-0.64	27	27
FOXO3	-0.001	0.15	-10000	0	-0.6	28	28
AKT1	0.035	0.11	0.41	16	-0.57	2	18
INSR	0.033	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.065	0.018	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.027	0.009	-10000	0	-10000	0	0
SORBS1	0.028	0.03	-10000	0	-0.64	1	1
CRK	0.029	0.005	-10000	0	-10000	0	0
PTPN1	0.022	0.01	-10000	0	-10000	0	0
CAV1	0	0.089	-10000	0	-0.33	32	32
CBL/APS/CAP/Crk-II/C3G	0.07	0.054	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.065	0.045	-10000	0	-0.38	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.046	0.047	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.043	0.039	-10000	0	-10000	0	0
RPS6KB1	0.029	0.1	0.38	14	-0.52	2	16
PARD6A	0.025	0.05	-10000	0	-0.64	3	3
CBL	0.028	0.029	-10000	0	-0.64	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.016	0.056	-10000	0	-0.49	6	6
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.028	0.076	-10000	0	-0.53	2	2
HRAS/GTP	0.016	0.043	-10000	0	-0.55	1	1
Insulin Receptor	0.033	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.075	0.047	-10000	0	-10000	0	0
PRKCI	0.032	0.051	-10000	0	-0.48	2	2
Insulin Receptor/Insulin/GRB14/PDK1	0.013	0.083	-10000	0	-0.62	2	2
SHC1	0.029	0.007	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.039	0.062	-10000	0	-0.45	7	7
PI3K	0.057	0.051	-10000	0	-10000	0	0
NCK2	0.029	0.006	-10000	0	-10000	0	0
RHOQ	0.029	0.005	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
HRAS/GDP	0.021	0.02	-10000	0	-0.44	1	1
AKT2	0.041	0.12	0.41	20	-0.57	2	22
PRKCZ	0.03	0.067	-10000	0	-0.59	5	5
SH2B2	0.022	0.054	-10000	0	-0.59	4	4
SHC/SHIP	0.034	0.051	-10000	0	-0.63	1	1
F2RL2	-0.005	0.14	-10000	0	-0.59	27	27
TRIP10	0.03	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.052	0.015	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.039	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.08	0.026	-10000	0	-10000	0	0
RAPGEF1	0.029	0.005	-10000	0	-10000	0	0
RASA1	0.025	0.03	-10000	0	-0.64	1	1
NCK1	0.027	0.03	-10000	0	-0.64	1	1
CBL/APS/CAP/Crk-II	0.062	0.052	-10000	0	-0.37	2	2
TC10/GDP	0.022	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.064	0.027	-10000	0	-10000	0	0
INPP5D	0.019	0.052	-10000	0	-0.43	4	4
SOS1	0.029	0.005	-10000	0	-10000	0	0
SGK1	-0.032	0.17	-10000	0	-0.62	40	40
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.029	0.005	-10000	0	-10000	0	0
IRS1	0.023	0.058	-10000	0	-0.64	4	4
p62DOK/RasGAP	0.039	0.063	-10000	0	-0.45	7	7
INS	0.023	0.007	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.019	0.051	-10000	0	-0.43	4	4
GRB2	0.029	0.005	-10000	0	-10000	0	0
EIF4EBP1	0.011	0.12	0.38	13	-0.58	5	18
PTPRA	0.031	0.006	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
TC10/GTP/CIP4	0.039	0.008	-10000	0	-10000	0	0
PDPK1	0.027	0.03	-10000	0	-0.64	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.036	0.03	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.048	0.041	-10000	0	-0.38	4	4
Insulin Receptor/Insulin/IRS3	0.041	0.011	-10000	0	-10000	0	0
Par3/Par6	0.039	0.09	-10000	0	-0.35	3	3

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.039	0.069	0.37	1	-0.38	1	2
adherens junction organization	0.002	0.093	0.25	5	-0.43	5	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.042	0.078	0.34	2	-10000	0	2
FMN1	-0.016	0.1	-10000	0	-0.43	12	12
mol:IP3	0.024	0.053	-10000	0	-0.36	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.001	0.078	-10000	0	-0.49	3	3
CTNNB1	0.022	0.014	-10000	0	-10000	0	0
AKT1	0.026	0.06	0.26	1	-10000	0	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.051	0.14	-10000	0	-0.57	21	21
CTNND1	0.032	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.073	-10000	0	-0.41	4	4
VASP	-0.001	0.075	-10000	0	-0.47	3	3
ZYX	0	0.073	-10000	0	-0.47	3	3
JUB	-0.002	0.074	-10000	0	-0.47	3	3
EGFR(dimer)	0.007	0.085	-10000	0	-0.46	4	4
E-cadherin/beta catenin-gamma catenin	0.023	0.088	-10000	0	-0.4	19	19
mol:PI-3-4-5-P3	0.033	0.069	-10000	0	-0.4	2	2
PIK3CA	0.03	0.03	-10000	0	-0.64	1	1
PI3K	0.034	0.071	-10000	0	-0.41	2	2
FYN	-0.2	0.14	-10000	0	-0.45	34	34
mol:Ca2+	0.024	0.053	-10000	0	-0.35	2	2
JUP	0.028	0.051	-10000	0	-0.63	3	3
PIK3R1	0.028	0.031	-10000	0	-0.64	1	1
mol:DAG	0.024	0.053	-10000	0	-0.36	2	2
CDH1	0.008	0.12	-10000	0	-0.62	18	18
RhoA/GDP	0.041	0.078	0.35	3	-10000	0	3
establishment of polarity of embryonic epithelium	0	0.074	-10000	0	-0.46	3	3
SRC	0.029	0.006	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
EGFR	0.02	0.067	-10000	0	-0.6	6	6
CASR	-0.22	0.15	-10000	0	-0.47	15	15
RhoA/GTP	0.029	0.051	-10000	0	-10000	0	0
AKT2	0.027	0.064	0.26	2	-0.4	1	3
actin cable formation	-0.015	0.1	-10000	0	-0.43	11	11
apoptosis	-0.028	0.07	0.36	2	-0.35	6	8
CTNNA1	0.024	0.013	-10000	0	-10000	0	0
mol:GDP	0.016	0.059	-10000	0	-10000	0	0
PIP5K1A	0	0.074	-10000	0	-0.42	4	4
PLCG1	0.024	0.054	-10000	0	-0.37	1	1
Rac1/GTP	0.018	0.085	-10000	0	-0.42	4	4
homophilic cell adhesion	0.001	0.003	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	0.038	0.036	-10000	0	-0.47	2	2
ATM	0.028	0.029	-10000	0	-0.64	1	1
UBE2D3	0.03	0.004	-10000	0	-10000	0	0
PRKDC	0.028	0.008	-10000	0	-10000	0	0
ATR	0.028	0.007	-10000	0	-10000	0	0
UBE2L3	0.03	0.004	-10000	0	-10000	0	0
FANCD2	0.021	0.022	-10000	0	-0.36	1	1
protein ubiquitination	0.067	0.06	-10000	0	-0.64	1	1
XRCC5	0.028	0.007	-10000	0	-10000	0	0
XRCC6	0.03	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.044	0.027	-10000	0	-10000	0	0
MRE11A	0.03	0.004	-10000	0	-10000	0	0
DNA-PK	0.054	0.02	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.003	0.11	-10000	0	-0.57	12	12
FANCF	0.03	0.004	-10000	0	-10000	0	0
BRCA1	0.029	0.004	-10000	0	-10000	0	0
CCNE1	0.022	0.071	-10000	0	-0.59	7	7
CDK2/Cyclin E1	0.037	0.055	-10000	0	-0.43	7	7
FANCG	0.029	0.006	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.039	0.037	-10000	0	-0.47	2	2
FANCE	0.028	0.028	-10000	0	-0.59	1	1
FANCC	0.029	0.006	-10000	0	-10000	0	0
NBN	0.028	0.007	-10000	0	-10000	0	0
FANCA	-0.095	0.25	-10000	0	-0.59	105	105
DNA repair	0.015	0.11	0.37	6	-0.62	4	10
BRCA1/BARD1/ubiquitin	0.039	0.037	-10000	0	-0.47	2	2
BARD1/DNA-PK	0.066	0.039	-10000	0	-0.37	2	2
FANCL	0.029	0.005	-10000	0	-10000	0	0
mRNA polyadenylation	-0.038	0.036	0.47	2	-10000	0	2
BRCA1/BARD1/CTIP/M/R/N Complex	0.028	0.046	-10000	0	-0.69	1	1
BRCA1/BACH1/BARD1/TopBP1	0.052	0.037	-10000	0	-0.4	2	2
BRCA1/BARD1/P53	0.066	0.038	-10000	0	-0.37	2	2
BARD1/CSTF1/BRCA1	0.053	0.034	-10000	0	-0.4	2	2
BRCA1/BACH1	0.029	0.004	-10000	0	-10000	0	0
BARD1	0.025	0.047	-10000	0	-0.48	4	4
PCNA	0.029	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.054	0.035	-10000	0	-0.4	2	2
BRCA1/BARD1/UbcH7	0.054	0.035	-10000	0	-0.4	2	2
BRCA1/BARD1/RAD51/PCNA	0.057	0.074	-10000	0	-0.39	3	3
BARD1/DNA-PK/P53	0.076	0.041	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.039	0.037	-10000	0	-0.47	2	2
BRCA1/BARD1/CTIP	0.048	0.047	-10000	0	-0.48	3	3
FA complex	-0.001	0.093	-10000	0	-0.45	5	5
BARD1/EWS	0.039	0.037	-10000	0	-0.47	2	2
RBBP8	0.021	0.038	-10000	0	-0.85	1	1
TP53	0.029	0.005	-10000	0	-10000	0	0
TOPBP1	0.028	0.007	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.064	0.038	0.36	2	-10000	0	2
BRCA1/BARD1	0.074	0.062	-10000	0	-0.65	1	1
CSTF1	0.029	0.006	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.018	0.034	-10000	0	-0.47	2	2
CDK2	0.029	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.013	0.1	-10000	0	-0.6	14	14
RAD50	0.023	0.013	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.039	0.037	-10000	0	-0.47	2	2
EWSR1	0.03	0.004	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.058	0.063	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.077	0.08	0.37	5	-0.58	1	6
alphaV/beta3 Integrin/Osteopontin/Src	0.047	0.043	-10000	0	-0.47	3	3
AP1	0.085	0.1	-10000	0	-0.6	3	3
ILK	0.047	0.058	-10000	0	-10000	0	0
bone resorption	0.043	0.092	-10000	0	-0.58	3	3
PTK2B	0.027	0.009	-10000	0	-10000	0	0
PYK2/p130Cas	0.072	0.066	-10000	0	-10000	0	0
ITGAV	0.033	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.023	0.095	-10000	0	-0.44	21	21
alphaV/beta3 Integrin/Osteopontin	0.064	0.059	-10000	0	-0.38	7	7
MAP3K1	0.042	0.059	-10000	0	-10000	0	0
JUN	0.029	0.007	-10000	0	-10000	0	0
MAPK3	0.039	0.064	-10000	0	-10000	0	0
MAPK1	0.042	0.063	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.007	-10000	0	-10000	0	0
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
MAPK8	0.038	0.07	0.41	1	-0.65	2	3
ITGB3	0.027	0.065	-10000	0	-0.62	5	5
NFKBIA	0.04	0.062	-10000	0	-10000	0	0
FOS	0.013	0.099	-10000	0	-0.63	12	12
CD44	0.008	0.11	-10000	0	-0.59	18	18
CHUK	0.029	0.006	-10000	0	-10000	0	0
PLAU	0.05	0.16	0.52	4	-1.1	8	12
NF kappa B1 p50/RelA	0.083	0.077	0.38	1	-0.56	1	2
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
RELA	0.03	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.045	0.052	-10000	0	-0.46	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.045	0.061	-10000	0	-10000	0	0
VAV3	0.029	0.083	-10000	0	-0.66	1	1
MAP3K14	0.046	0.065	-10000	0	-10000	0	0
ROCK2	0.025	0.053	-10000	0	-0.56	4	4
SPP1	0.03	0.051	-10000	0	-0.63	3	3
RAC1	0.027	0.009	-10000	0	-10000	0	0
Rac1/GTP	0.037	0.074	-10000	0	-0.61	1	1
MMP2	0.053	0.1	0.43	2	-0.51	7	9

×

Hedgehog signaling events mediated by Gli proteins

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.029	0.006	-10000	0	-10000	0	0
HDAC2	0.028	0.008	-10000	0	-10000	0	0
GNB1/GNG2	0.049	0.031	-10000	0	-0.4	1	1
forebrain development	0.047	0.11	0.47	5	-0.48	5	10
GNAO1	0.024	0.055	-10000	0	-0.6	4	4
SMO/beta Arrestin2	0.039	0.037	-10000	0	-0.5	2	2
SMO	0.026	0.031	-10000	0	-0.63	1	1
ARRB2	0.029	0.033	-10000	0	-0.71	1	1
GLI3/SPOP	0.056	0.09	-10000	0	-0.5	8	8
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.028	0.008	-10000	0	-10000	0	0
GNAI2	0.022	0.014	-10000	0	-10000	0	0
SIN3/HDAC complex	0.059	0.076	-10000	0	-0.33	18	18
GNAI1	0.026	0.03	-10000	0	-0.63	1	1
XPO1	0.03	0.011	-10000	0	-10000	0	0
GLI1/Su(fu)	0.04	0.096	-10000	0	-0.58	5	5
SAP30	0.008	0.11	-10000	0	-0.59	18	18
mol:GDP	0.026	0.031	-10000	0	-0.63	1	1
MIM/GLI2A	0.027	0.03	-10000	0	-10000	0	0
IFT88	0.028	0.029	-10000	0	-0.64	1	1
GNAI3	0.029	0.006	-10000	0	-10000	0	0
GLI2	0.071	0.077	0.31	12	-10000	0	12
GLI3	0.042	0.096	0.3	3	-0.56	8	11
CSNK1D	0.029	0.005	-10000	0	-10000	0	0
CSNK1E	0.03	0.004	-10000	0	-10000	0	0
SAP18	0.029	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.028	0.029	-10000	0	-0.63	1	1
GNG2	0.028	0.008	-10000	0	-10000	0	0
Gi family/GTP	0.024	0.044	-10000	0	-0.39	3	3
SIN3B	0.03	0.003	-10000	0	-10000	0	0
SIN3A	0.03	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.046	0.1	-10000	0	-0.62	8	8
GLI2/Su(fu)	0.072	0.067	0.27	2	-0.57	1	3
FOXA2	-0.005	0.21	-10000	0	-1	14	14
neural tube patterning	0.047	0.11	0.47	5	-0.48	5	10
SPOP	0.029	0.005	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.046	0.048	-10000	0	-0.54	1	1
GNB1	0.029	0.006	-10000	0	-10000	0	0
CSNK1G2	0.028	0.029	-10000	0	-0.64	1	1
CSNK1G3	0.023	0.012	-10000	0	-10000	0	0
MTSS1	0.027	0.03	-10000	0	-10000	0	0
embryonic limb morphogenesis	0.047	0.11	0.47	5	-0.48	5	10
SUFU	0.03	0.032	-10000	0	-0.58	1	1
LGALS3	0.015	0.09	-10000	0	-0.6	11	11
catabolic process	0.1	0.12	0.38	10	-0.56	5	15
GLI3A/CBP	0.031	0.044	-10000	0	-0.36	2	2
KIF3A	0.023	0.013	-10000	0	-10000	0	0
GLI1	0.047	0.11	0.48	5	-0.49	5	10
RAB23	0.029	0.006	-10000	0	-10000	0	0
CSNK1A1	0.023	0.013	-10000	0	-10000	0	0
IFT172	0.029	0.005	-10000	0	-10000	0	0
RBBP7	0.03	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.036	0.079	-10000	0	-0.51	6	6
GNAZ	0.026	0.05	-10000	0	-0.64	3	3
RBBP4	0.027	0.03	-10000	0	-0.64	1	1
CSNK1G1	0.03	0.003	-10000	0	-10000	0	0
PIAS1	0.03	0.003	-10000	0	-10000	0	0
PRKACA	0.03	0.002	-10000	0	-10000	0	0
GLI2/SPOP	0.084	0.065	0.29	6	-10000	0	6
STK36	0.03	0.011	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.029	0.038	-10000	0	-0.44	1	1
PTCH1	0.047	0.11	0.48	4	-0.97	1	5
MIM/GLI1	0.049	0.14	0.45	2	-0.55	5	7
CREBBP	0.031	0.044	-10000	0	-0.36	2	2
Su(fu)/SIN3/HDAC complex	0.03	0.1	0.26	1	-0.54	11	12

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.023	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.05	0.029	-10000	0	-0.37	1	1
CDKN1B	0.019	0.076	-10000	0	-0.57	1	1
CDKN1A	0.019	0.075	-10000	0	-0.58	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.028	0.008	-10000	0	-10000	0	0
FOXO3	0.019	0.071	-10000	0	-0.58	2	2
AKT1	0.025	0.031	-10000	0	-0.6	1	1
BAD	0.027	0.04	-10000	0	-0.61	2	2
AKT3	0.019	0.018	-10000	0	-0.37	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.016	0.08	-10000	0	-0.58	2	2
AKT1/ASK1	0.026	0.091	-10000	0	-0.5	4	4
BAD/YWHAZ	0.055	0.031	-10000	0	-0.39	2	2
RICTOR	0.027	0.009	-10000	0	-10000	0	0
RAF1	0.021	0.014	-10000	0	-10000	0	0
JNK cascade	-0.025	0.088	0.49	4	-10000	0	4
TSC1	0.021	0.067	-10000	0	-0.57	1	1
YWHAZ	0.028	0.007	-10000	0	-10000	0	0
AKT1/RAF1	0.02	0.091	-10000	0	-0.51	4	4
EP300	0.028	0.029	-10000	0	-0.64	1	1
mol:GDP	0.012	0.072	-10000	0	-0.6	2	2
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.014	0.079	-10000	0	-0.58	2	2
YWHAQ	0.029	0.005	-10000	0	-10000	0	0
TBC1D4	0.017	0.015	-10000	0	-0.31	1	1
MAP3K5	0.028	0.008	-10000	0	-10000	0	0
MAPKAP1	0.029	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.032	0.082	0.32	9	-0.25	10	19
YWHAH	0.03	0.004	-10000	0	-10000	0	0
AKT1S1	0.017	0.079	-10000	0	-0.58	2	2
CASP9	0.02	0.07	-10000	0	-0.59	1	1
YWHAB	0.029	0.006	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.033	0.094	0.34	5	-0.45	4	9
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.052	0.029	-10000	0	-0.4	1	1
YWHAE	0.029	0.005	-10000	0	-10000	0	0
SRC	0.029	0.006	-10000	0	-10000	0	0
AKT2/p21CIP1	0.016	0.078	-10000	0	-0.47	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.027	-10000	0	-10000	0	0
CHUK	0.018	0.076	-10000	0	-0.58	2	2
BAD/BCL-XL	0.039	0.093	-10000	0	-0.47	5	5
mTORC2	0.033	0.013	-10000	0	-10000	0	0
AKT2	0.02	0.018	-10000	0	-0.37	1	1
FOXO1-3a-4/14-3-3 family	0.036	0.11	0.3	9	-0.41	11	20
PDPK1	0.027	0.03	-10000	0	-0.64	1	1
MDM2	0.02	0.077	-10000	0	-0.57	1	1
MAPKKK cascade	-0.019	0.089	0.5	4	-10000	0	4
MDM2/Cbp/p300	0.047	0.095	0.32	3	-0.44	5	8
TSC1/TSC2	0.026	0.074	0.28	11	-0.56	1	12
proteasomal ubiquitin-dependent protein catabolic process	0.044	0.091	0.31	3	-0.42	5	8
glucose import	0.01	0.058	-10000	0	-0.35	11	11
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.053	0.24	3	-0.32	2	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.008	0.055	-10000	0	-0.36	11	11
GSK3A	0.017	0.079	-10000	0	-0.58	2	2
FOXO1	0.017	0.079	-10000	0	-0.58	2	2
GSK3B	0.018	0.073	-10000	0	-0.58	2	2
SFN	-0.041	0.2	-10000	0	-0.59	59	59
G1/S transition of mitotic cell cycle	0.024	0.079	0.34	3	-0.52	3	6
p27Kip1/14-3-3 family	0.039	0.069	0.27	2	-0.38	3	5
PRKACA	0.03	0.002	-10000	0	-10000	0	0
KPNA1	0.028	0.008	-10000	0	-10000	0	0
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
YWHAG	0.027	0.009	-10000	0	-10000	0	0
RHEB	0.027	0.009	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0

×

Nectin adhesion 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.023	0.013	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.037	0.051	-10000	0	-0.47	5	5
PTK2	0.029	0.078	-10000	0	-0.7	1	1
positive regulation of JNK cascade	0.01	0.1	-10000	0	-0.34	14	14
CDC42/GDP	0.036	0.14	0.37	3	-0.46	9	12
Rac1/GDP	0.03	0.13	-10000	0	-0.5	5	5
RAP1B	0.029	0.005	-10000	0	-10000	0	0
RAP1A	0.029	0.006	-10000	0	-10000	0	0
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
CDC42/GTP	0.021	0.13	-10000	0	-0.43	14	14
nectin-3/I-afadin	0.036	0.037	-10000	0	-0.47	2	2
RAPGEF1	0.019	0.12	0.3	2	-0.47	3	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0.13	-10000	0	-0.54	3	3
PDGFB-D/PDGFRB	0.023	0.013	-10000	0	-10000	0	0
TLN1	0.016	0.016	-10000	0	-10000	0	0
Rap1/GTP	0.012	0.09	-10000	0	-0.39	1	1
IQGAP1	0.03	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.02	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.036	0.037	-10000	0	-0.47	2	2
PVR	0.03	0.003	-10000	0	-10000	0	0
Necl-5(dimer)	0.03	0.003	-10000	0	-10000	0	0
mol:GDP	0.022	0.16	0.39	3	-0.54	13	16
MLLT4	0.027	0.008	-10000	0	-10000	0	0
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
PI3K	0.055	0.056	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.04	0.013	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.013	0.1	-10000	0	-0.37	10	10
PVRL1	0.03	0.003	-10000	0	-10000	0	0
PVRL3	0.024	0.044	-10000	0	-0.53	3	3
PVRL2	0.03	0.003	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
CDH1	0.007	0.12	-10000	0	-0.62	18	18
CLDN1	0.022	0.063	-10000	0	-0.62	5	5
JAM-A/CLDN1	0.057	0.055	-10000	0	-0.36	5	5
SRC	0.006	0.14	-10000	0	-0.6	3	3
ITGB3	0.023	0.065	-10000	0	-0.64	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.04	0.013	-10000	0	-10000	0	0
FARP2	0.015	0.17	-10000	0	-0.64	15	15
RAC1	0.027	0.009	-10000	0	-10000	0	0
CTNNA1	0.023	0.013	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.049	0.037	-10000	0	-0.4	2	2
nectin-1/I-afadin	0.04	0.013	-10000	0	-10000	0	0
nectin-2/I-afadin	0.04	0.013	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.036	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.05	0.037	-10000	0	-0.4	2	2
CDC42/GTP/IQGAP1/filamentous actin	0.039	0.009	-10000	0	-10000	0	0
F11R	0.029	0.007	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.01	0.1	-10000	0	-0.34	14	14
alphaV/beta3 Integrin/Talin	0.047	0.051	-10000	0	-0.49	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.04	0.013	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.04	0.013	-10000	0	-10000	0	0
PIP5K1C	0.017	0.017	-10000	0	-10000	0	0
VAV2	0.016	0.17	-10000	0	-0.63	12	12
RAP1/GDP	0.036	0.13	-10000	0	-0.44	2	2
ITGAV	0.029	0.007	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.049	0.037	-10000	0	-0.4	2	2
nectin-3(dimer)/I-afadin/I-afadin	0.036	0.037	-10000	0	-0.47	2	2
Rac1/GTP	0.021	0.13	-10000	0	-0.46	9	9
PTPRM	0.018	0.019	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.04	0.075	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.029	0.006	-10000	0	-10000	0	0

×

Arf6 trafficking 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
SLC2A4	0.015	0.097	-10000	0	-0.64	11	11
CLTC	0.019	0.085	-10000	0	-0.39	5	5
calcium ion-dependent exocytosis	0.027	0.028	0.2	1	-10000	0	1
Dynamin 2/GTP	0.032	0.019	-10000	0	-0.34	1	1
EXOC4	0.027	0.009	-10000	0	-10000	0	0
CD59	0.016	0.064	-10000	0	-0.3	4	4
CPE	0.005	0.077	-10000	0	-0.37	21	21
CTNNB1	0.021	0.014	-10000	0	-10000	0	0
membrane fusion	0.02	0.015	-10000	0	-10000	0	0
CTNND1	0.026	0.025	-10000	0	-10000	0	0
DNM2	0.03	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.024	0.049	0.26	1	-0.44	1	2
TSHR	-0.025	0.12	-10000	0	-0.37	60	60
INS	0.017	0.038	-10000	0	-0.77	1	1
BIN1	0.029	0.005	-10000	0	-10000	0	0
mol:Choline	0.02	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.018	-10000	0	-0.37	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.028	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.032	0.019	-10000	0	-0.33	1	1
JUP	0.014	0.068	-10000	0	-0.38	1	1
ASAP2/amphiphysin II	0.051	0.025	-10000	0	-0.37	1	1
ARF6/GTP	0.021	0.006	-10000	0	-10000	0	0
CDH1	0.009	0.078	-10000	0	-0.45	3	3
clathrin-independent pinocytosis	0.021	0.006	-10000	0	-10000	0	0
MAPK8IP3	-0.014	0.16	-10000	0	-0.59	36	36
positive regulation of endocytosis	0.021	0.006	-10000	0	-10000	0	0
EXOC2	0.029	0.006	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.036	0.022	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.029	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.021	0.077	0.51	1	-10000	0	1
positive regulation of phagocytosis	0.02	0.007	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.009	0.1	-10000	0	-0.37	36	36
ACAP1	0.012	0.036	-10000	0	-0.27	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.008	0.062	-10000	0	-0.32	5	5
clathrin heavy chain/ACAP1	0.022	0.069	-10000	0	-0.49	1	1
JIP4/KLC1	0.052	0.018	-10000	0	-10000	0	0
EXOC1	0.03	0.004	-10000	0	-10000	0	0
exocyst	0.036	0.022	-10000	0	-10000	0	0
RALA/GTP	0.02	0.007	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.037	0.012	-10000	0	-10000	0	0
receptor recycling	0.021	0.006	-10000	0	-10000	0	0
CTNNA1	0.021	0.027	-10000	0	-10000	0	0
NME1	0.019	0.018	-10000	0	-0.37	1	1
clathrin coat assembly	0.019	0.088	-10000	0	-0.38	5	5
IL2RA	-0.018	0.093	-10000	0	-0.38	7	7
VAMP3	0.02	0.007	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.02	0.08	-10000	0	-0.44	4	4
EXOC6	0.029	0.006	-10000	0	-10000	0	0
PLD1	0.021	0.009	-10000	0	-10000	0	0
PLD2	0.021	0.009	-10000	0	-10000	0	0
EXOC5	0.028	0.008	-10000	0	-10000	0	0
PIP5K1C	0.024	0.046	-10000	0	-0.45	1	1
SDC1	0.013	0.074	-10000	0	-0.51	2	2
ARF6/GDP	0.028	0.02	-10000	0	-0.37	1	1
EXOC7	0.029	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.023	0.08	-10000	0	-0.52	1	1
mol:Phosphatidic acid	0.02	0.015	-10000	0	-10000	0	0
endocytosis	-0.05	0.025	0.37	1	-10000	0	1
SCAMP2	0.03	0.003	-10000	0	-10000	0	0
ADRB2	0.063	0.1	0.33	6	-0.51	1	7
EXOC3	0.027	0.009	-10000	0	-10000	0	0
ASAP2	0.028	0.029	-10000	0	-0.64	1	1
Dynamin 2/GDP	0.035	0.02	-10000	0	-0.33	1	1
KLC1	0.028	0.008	-10000	0	-10000	0	0
AVPR2	-0.12	0.19	0.3	1	-0.58	25	26
RALA	0.027	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.039	0.08	-10000	0	-0.49	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0.067	0.84	1	-10000	0	1
VDR	0.025	0.05	-10000	0	-0.64	3	3
FAM120B	0.027	0.008	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.057	0.046	-10000	0	-0.34	1	1
RXRs/LXRs/DNA/Oxysterols	0.062	0.056	-10000	0	-10000	0	0
MED1	0.029	0.004	-10000	0	-10000	0	0
mol:9cRA	0.006	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.012	0.074	-10000	0	-10000	0	0
RXRs/NUR77	0.065	0.085	-10000	0	-0.37	6	6
RXRs/PPAR	0.034	0.039	-10000	0	-0.55	1	1
NCOR2	0.029	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.038	-10000	0	-0.47	3	3
RARs/VDR/DNA/Vit D3	0.045	0.05	-10000	0	-0.35	2	2
RARA	0.029	0.004	-10000	0	-10000	0	0
NCOA1	0.029	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.025	0.05	-10000	0	-0.63	3	3
RARs/RARs/DNA/9cRA	0.037	0.036	-10000	0	-0.35	2	2
RARG	0.029	0.005	-10000	0	-10000	0	0
RPS6KB1	0.02	0.071	0.5	9	-0.44	1	10
RARs/THRs/DNA/SMRT	0.013	0.074	-10000	0	-10000	0	0
THRA	0.028	0.029	-10000	0	-0.64	1	1
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.038	-10000	0	-0.47	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	0.067	0.05	0.33	1	-0.39	1	2
NR1H4	0.011	0.11	-10000	0	-0.64	14	14
RXRs/LXRs/DNA	0.1	0.062	-10000	0	-10000	0	0
NR1H2	0.034	0.031	-10000	0	-0.63	1	1
NR1H3	0.036	0.01	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.069	0.054	-10000	0	-0.35	3	3
NR4A1	0.012	0.11	-10000	0	-0.63	14	14
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.027	0.073	-10000	0	-0.43	9	9
RXRG	0.027	0.057	-10000	0	-0.61	4	4
RXR alpha/CCPG	0.043	0.017	-10000	0	-10000	0	0
RXRA	0.034	0.011	-10000	0	-10000	0	0
RXRB	0.035	0.012	-10000	0	-10000	0	0
THRB	-0.015	0.14	-10000	0	-0.57	32	32
PPARG	0.021	0.014	-10000	0	-10000	0	0
PPARD	0.029	0.006	-10000	0	-10000	0	0
TNF	0.056	0.11	-10000	0	-1	4	4
mol:Oxysterols	0.006	0.006	-10000	0	-10000	0	0
cholesterol transport	0.062	0.056	-10000	0	-10000	0	0
PPARA	0.03	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.043	-10000	0	-0.64	2	2
RXRs/NUR77/BCL2	0.027	0.059	-10000	0	-0.46	2	2
SREBF1	0.062	0.051	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.067	0.05	0.33	1	-0.39	1	2
ABCA1	0.061	0.058	-10000	0	-10000	0	0
RARs/THRs	0.037	0.1	-10000	0	-10000	0	0
RXRs/FXR	0.066	0.084	-10000	0	-0.42	2	2
BCL2	0.029	0.005	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.006	-10000	0	-10000	0	0
NFATC1	0.045	0.071	0.37	3	-0.44	1	4
NFATC2	0.037	0.068	0.23	7	-0.26	12	19
NFATC3	0.025	0.031	-10000	0	-0.35	3	3
YWHAE	0.029	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0	0.085	0.31	2	-0.37	9	11
Exportin 1/Ran/NUP214	0.056	0.018	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.025	0.078	-10000	0	-0.43	3	3
BCL2/BAX	0.043	0.009	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.021	0.01	-10000	0	-10000	0	0
BAX	0.03	0.003	-10000	0	-10000	0	0
MAPK14	0.029	0.006	-10000	0	-10000	0	0
BAD	0.027	0.04	-10000	0	-0.61	2	2
CABIN1/MEF2D	0.014	0.082	0.31	1	-0.39	5	6
Calcineurin A alpha-beta B1/BCL2	0.029	0.005	-10000	0	-10000	0	0
FKBP8	0.029	0.029	-10000	0	-0.64	1	1
activation-induced cell death of T cells	-0.014	0.081	0.38	5	-0.31	1	6
KPNB1	0.029	0.005	-10000	0	-10000	0	0
KPNA2	0.029	0.005	-10000	0	-10000	0	0
XPO1	0.029	0.005	-10000	0	-10000	0	0
SFN	-0.041	0.2	-10000	0	-0.59	59	59
MAP3K8	0.027	0.038	-10000	0	-0.59	2	2
NFAT4/CK1 alpha	0.032	0.03	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.074	0.089	-10000	0	-0.44	3	3
CABIN1	0	0.084	0.31	2	-0.38	8	10
CALM1	0.028	0.009	-10000	0	-10000	0	0
RAN	0.029	0.006	-10000	0	-10000	0	0
MAP3K1	0.027	0.009	-10000	0	-10000	0	0
CAMK4	0.023	0.031	-10000	0	-0.64	1	1
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.029	0.006	-10000	0	-10000	0	0
YWHAH	0.03	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.039	0.034	-10000	0	-0.47	2	2
YWHAB	0.029	0.006	-10000	0	-10000	0	0
MAPK8	0.027	0.041	-10000	0	-0.64	2	2
MAPK9	0.022	0.013	-10000	0	-10000	0	0
YWHAG	0.027	0.009	-10000	0	-10000	0	0
FKBP1A	0.029	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.07	0.079	-10000	0	-0.45	1	1
PRKCH	0.028	0.008	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.041	0.027	-10000	0	-0.47	1	1
CASP3	0.03	0.004	-10000	0	-10000	0	0
PIM1	0.029	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
apoptosis	0.025	0.016	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.061	-10000	0	-0.36	5	5
PRKCB	0.022	0.062	-10000	0	-0.61	5	5
PRKCE	0.028	0.029	-10000	0	-0.64	1	1
JNK2/NFAT4	0.026	0.044	-10000	0	-0.4	1	1
BAD/BCL-XL	0.041	0.032	-10000	0	-0.45	2	2
PRKCD	0.02	0.03	-10000	0	-0.59	1	1
NUP214	0.029	0.005	-10000	0	-10000	0	0
PRKCZ	0.025	0.051	-10000	0	-0.64	3	3
PRKCA	0.029	0.005	-10000	0	-10000	0	0
PRKCG	-0.001	0.12	-10000	0	-0.6	21	21
PRKCQ	0.012	0.1	-10000	0	-0.57	15	15
FKBP38/BCL2	0.042	0.024	-10000	0	-0.47	1	1
EP300	0.028	0.03	-10000	0	-0.63	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.029	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.057	0.075	0.35	2	-0.39	1	3
CaM/Ca2+/FKBP38	0.037	0.024	-10000	0	-0.42	1	1
FKBP12/FK506	0.021	0.004	-10000	0	-10000	0	0
CSNK1A1	0.017	0.012	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.031	0.026	-10000	0	-0.39	1	1
NFATc/ERK1	0.054	0.07	-10000	0	-0.41	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.025	0.079	-10000	0	-0.44	3	3
NR4A1	0.051	0.12	-10000	0	-0.58	13	13
GSK3B	0.028	0.008	-10000	0	-10000	0	0
positive T cell selection	0.025	0.031	-10000	0	-0.35	3	3
NFAT1/CK1 alpha	0.021	0.038	-10000	0	-10000	0	0
RCH1/ KPNB1	0.043	0.008	-10000	0	-10000	0	0
YWHAQ	0.029	0.005	-10000	0	-10000	0	0
PRKACA	0.03	0.003	-10000	0	-10000	0	0
AKAP5	0.025	0.042	-10000	0	-0.64	2	2
MEF2D	0.029	0.009	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.028	0.007	-10000	0	-10000	0	0
NFATc/p38 alpha	0.06	0.071	0.37	3	-0.39	1	4
CREBBP	0.029	0.008	-10000	0	-10000	0	0
BCL2	0.029	0.005	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.029	0.006	-10000	0	-10000	0	0
HDAC3	0.023	0.013	-10000	0	-10000	0	0
VDR	0.025	0.05	-10000	0	-0.64	3	3
Cbp/p300/PCAF	0.041	0.045	-10000	0	-0.76	1	1
EP300	0.028	0.029	-10000	0	-0.64	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.028	0.051	-10000	0	-0.33	4	4
KAT2B	0.02	0.032	-10000	0	-0.64	1	1
MAPK14	0.029	0.006	-10000	0	-10000	0	0
AKT1	0	0.054	0.22	1	-10000	0	1
RAR alpha/9cRA/Cyclin H	0.05	0.057	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.027	0.053	-10000	0	-0.44	1	1
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.025	0.056	-10000	0	-0.37	6	6
NCOR2	0.029	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.038	-10000	0	-0.47	3	3
RXRs/RARs/NRIP1/9cRA	0.03	0.078	-10000	0	-0.53	1	1
NCOA2	0.015	0.091	-10000	0	-0.64	10	10
NCOA3	0.029	0.006	-10000	0	-10000	0	0
NCOA1	0.029	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.025	0.05	-10000	0	-0.63	3	3
RARG	0.03	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.04	0.008	-10000	0	-10000	0	0
MAPK3	0.03	0.006	-10000	0	-10000	0	0
MAPK1	0.03	0.004	-10000	0	-10000	0	0
MAPK8	0.028	0.041	-10000	0	-0.63	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.045	0.07	-10000	0	-0.54	1	1
RARA	0.022	0.04	-10000	0	-0.26	3	3
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.02	0.08	-10000	0	-0.47	9	9
PRKCA	0.032	0.006	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.004	0.1	0.36	1	-0.52	3	4
RXRG	0.017	0.062	-10000	0	-0.62	1	1
RXRA	0.028	0.044	-10000	0	-10000	0	0
RXRB	0.019	0.063	-10000	0	-0.5	3	3
VDR/Vit D3/DNA	0.019	0.038	-10000	0	-0.47	3	3
RBP1	0.024	0.055	-10000	0	-0.6	4	4
CRBP1/9-cic-RA	0.018	0.041	-10000	0	-0.44	4	4
RARB	0.021	0.043	-10000	0	-0.64	2	2
PRKCG	0.002	0.12	-10000	0	-0.59	21	21
MNAT1	0.028	0.008	-10000	0	-10000	0	0
RAR alpha/RXRs	0.024	0.076	-10000	0	-0.53	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.032	0.073	0.3	1	-0.43	2	3
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.11	0.28	8	-0.36	5	13
RXRs/RARs/NRIP1/9cRA/HDAC3	0.014	0.1	0.4	1	-0.51	2	3
positive regulation of DNA binding	0.037	0.049	-10000	0	-10000	0	0
NRIP1	-0.008	0.12	-10000	0	-10000	0	0
RXRs/RARs	-0.015	0.12	-10000	0	-0.49	4	4
RXRs/RXRs/DNA/9cRA	0.028	0.062	-10000	0	-0.48	2	2
PRKACA	0.03	0.002	-10000	0	-10000	0	0
CDK7	0.027	0.009	-10000	0	-10000	0	0
TFIIH	0.051	0.023	-10000	0	-10000	0	0
RAR alpha/9cRA	0.053	0.054	-10000	0	-10000	0	0
CCNH	0.026	0.01	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.048	0.025	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.03	0.004	-9999	-10000	0	0
Rac1/GDP	0.023	0.013	-9999	-10000	0	0
DOCK1	0.028	0.03	-9999	-0.64	1	1
ITGA4	0.01	0.11	-9999	-0.59	16	16
RAC1	0.027	0.009	-9999	-10000	0	0
alpha4/beta7 Integrin	0.027	0.082	-9999	-0.43	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.029	0.005	-9999	-10000	0	0
alpha4/beta1 Integrin	0.044	0.075	-9999	-0.37	16	16
alpha4/beta7 Integrin/Paxillin	0.04	0.068	-9999	-10000	0	0
lamellipodium assembly	0.038	0.058	-9999	-0.62	2	2
PIK3CA	0.027	0.03	-9999	-0.64	1	1
PI3K	0.037	0.035	-9999	-0.47	2	2
ARF6	0.028	0.008	-9999	-10000	0	0
TLN1	0.029	0.006	-9999	-10000	0	0
PXN	0.023	0.005	-9999	-10000	0	0
PIK3R1	0.026	0.03	-9999	-0.64	1	1
ARF6/GTP	0.049	0.064	-9999	-10000	0	0
cell adhesion	0.051	0.068	-9999	-10000	0	0
CRKL/CBL	0.042	0.024	-9999	-0.47	1	1
alpha4/beta1 Integrin/Paxillin	0.04	0.068	-9999	-10000	0	0
ITGB1	0.029	0.004	-9999	-10000	0	0
ITGB7	0.029	0.005	-9999	-10000	0	0
ARF6/GDP	0.024	0.012	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.045	0.086	-9999	-10000	0	0
p130Cas/Crk/Dock1	0.054	0.033	-9999	-0.4	2	2
VCAM1	0.015	0.089	-9999	-0.53	13	13
alpha4/beta1 Integrin/Paxillin/Talin	0.053	0.069	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.054	0.069	-9999	-10000	0	0
BCAR1	0.028	0.03	-9999	-0.64	1	1
mol:GDP	-0.052	0.068	-9999	-10000	0	0
CBL	0.028	0.029	-9999	-0.64	1	1
PRKACA	0.03	0.002	-9999	-10000	0	0
GIT1	0.029	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.053	0.069	-9999	-10000	0	0
Rac1/GTP	0.04	0.065	-9999	-0.72	2	2

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.042	0.03	-10000	0	-0.43	2	2
FBXW11	0.023	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.032	0.041	-10000	0	-0.41	4	4
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.06	-10000	0	-10000	0	0
NFKBIA	0.019	0.044	-10000	0	-0.33	2	2
MAPK14	0.029	0.006	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.027	0.026	-10000	0	-0.4	1	1
ARRB2	0.019	0.028	-10000	0	-0.62	1	1
REL	0.025	0.053	-10000	0	-0.56	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.034	0.033	-10000	0	-0.39	2	2
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.035	0.022	-10000	0	-0.4	1	1
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
NF kappa B1 p50 dimer	0.025	0.023	-10000	0	-0.47	1	1
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
NFKB1	0.02	0.023	-10000	0	-0.47	1	1
RELA	0.03	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.023	0.042	-10000	0	-0.28	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.037	0.068	-10000	0	-0.5	1	1
SRC	0.029	0.006	-10000	0	-10000	0	0
PI3K	0.037	0.035	-10000	0	-0.47	2	2
NF kappa B1 p50/RelA	0.024	0.043	-10000	0	-0.29	2	2
IKBKB	0.028	0.008	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.023	0.013	-10000	0	-10000	0	0
SYK	0.027	0.033	-10000	0	-0.48	2	2
I kappa B alpha/PIK3R1	0.022	0.063	0.28	1	-0.41	2	3
cell death	0.035	0.065	-10000	0	-0.48	1	1
NF kappa B1 p105/c-Rel	0.032	0.041	-10000	0	-0.41	4	4
LCK	0.003	0.12	-10000	0	-0.59	22	22
BCL3	0.027	0.038	-10000	0	-0.59	2	2

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.029	0.006	-10000	0	-10000	0	0
PTK2	0.029	0.007	-10000	0	-10000	0	0
CRKL	0.025	0.038	-10000	0	-10000	0	0
GRB2/SOS1/SHC	0.056	0.017	-10000	0	-10000	0	0
HRAS	0.029	0.027	-10000	0	-0.59	1	1
IRS1/Crk	0.03	0.035	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/PTP1B	0.052	0.042	-10000	0	-0.33	2	2
AKT1	0.036	0.068	0.31	6	-0.61	1	7
BAD	0.032	0.073	0.3	6	-0.82	1	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.038	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.035	0.037	-10000	0	-10000	0	0
RAF1	-0.04	0.18	0.34	2	-0.59	2	4
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.064	0.042	-10000	0	-10000	0	0
YWHAZ	0.028	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.033	0.039	-10000	0	-0.27	6	6
PIK3CA	0.027	0.03	-10000	0	-0.64	1	1
RPS6KB1	0.04	0.072	0.32	7	-0.61	1	8
GNB2L1	0.023	0.013	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.038	0.16	0.33	8	-0.48	2	10
PXN	0.029	0.005	-10000	0	-10000	0	0
PIK3R1	0.026	0.03	-10000	0	-0.64	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.043	0.01	-10000	0	-10000	0	0
HRAS/GTP	0.031	0.034	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.078	0.041	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.032	0.016	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.05	0.041	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	0.065	0.046	-10000	0	-10000	0	0
IGF1R	0.032	0.016	-10000	0	-10000	0	0
IGF1	0.026	0.06	-10000	0	-0.57	5	5
IRS2/Crk	0.032	0.054	-10000	0	-0.32	4	4
PI3K	0.058	0.052	-10000	0	-0.34	1	1
apoptosis	-0.048	0.072	0.66	1	-0.31	9	10
HRAS/GDP	0.021	0.02	-10000	0	-0.44	1	1
PRKCD	0.029	0.05	-10000	0	-0.44	3	3
RAF1/14-3-3 E	-0.037	0.18	0.34	4	-0.5	2	6
BAD/14-3-3	0.05	0.075	0.33	6	-0.73	1	7
PRKCZ	0.036	0.071	0.32	5	-0.61	1	6
Crk/p130 Cas/Paxillin/FAK1	0.041	0.045	-10000	0	-0.51	1	1
PTPN1	0.029	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.025	0.039	-10000	0	-0.36	3	3
BCAR1	0.028	0.03	-10000	0	-0.64	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.061	0.044	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.029	0.005	-10000	0	-10000	0	0
IRS1/NCK2	0.038	0.039	-10000	0	-10000	0	0
GRB10	0.027	0.009	-10000	0	-10000	0	0
PTPN11	0.026	0.039	-10000	0	-10000	0	0
IRS1	0.022	0.041	0.21	1	-0.27	6	7
IRS2	0.02	0.057	-10000	0	-0.33	7	7
IGF-1R heterotetramer/IGF1	0.039	0.048	-10000	0	-0.4	5	5
GRB2	0.029	0.005	-10000	0	-10000	0	0
PDPK1	0.043	0.071	0.32	7	-0.64	1	8
YWHAE	0.029	0.005	-10000	0	-10000	0	0
PRKD1	0.041	0.05	-10000	0	-0.37	4	4
SHC1	0.029	0.007	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.068	0.031	-10000	0	-0.37	1	1
HDAC3	0.023	0.013	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.008	0.002	-10000	0	-10000	0	0
GATA1/HDAC4	0.023	0.09	-10000	0	-0.43	19	19
GATA1/HDAC5	0.023	0.094	-10000	0	-0.44	21	21
GATA2/HDAC5	0.029	0.076	-10000	0	-0.47	11	11
HDAC5/BCL6/BCoR	0.055	0.026	-10000	0	-0.4	1	1
HDAC9	0.027	0.009	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.043	0.033	-10000	0	-0.37	1	1
HDAC4/ANKRA2	0.038	0.016	-10000	0	-10000	0	0
HDAC5/YWHAB	0.041	0.025	-10000	0	-0.47	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.022	0.008	-10000	0	-10000	0	0
GATA2	0.014	0.096	-10000	0	-0.61	12	12
HDAC4/RFXANK	0.041	0.023	-10000	0	-0.43	1	1
BCOR	0.03	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.028	0.029	-10000	0	-0.64	1	1
HDAC5	0.028	0.029	-10000	0	-0.64	1	1
GNB1/GNG2	0.04	0.014	-10000	0	-10000	0	0
Histones	0.032	0.045	-10000	0	-0.72	1	1
ADRBK1	0.03	0.003	-10000	0	-10000	0	0
HDAC4	0.028	0.007	-10000	0	-10000	0	0
XPO1	0.029	0.005	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.038	0.027	-10000	0	-0.47	1	1
HDAC4/Ubc9	0.04	0.013	-10000	0	-10000	0	0
HDAC7	0.029	0.005	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.042	0.024	-10000	0	-0.47	1	1
TUBA1B	0.029	0.005	-10000	0	-10000	0	0
HDAC6	0.03	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.041	0.032	-10000	0	-0.45	2	2
CAMK4	0.023	0.031	-10000	0	-0.64	1	1
Tubulin/HDAC6	0.056	0.026	-10000	0	-0.4	1	1
SUMO1	0.029	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.029	0.006	-10000	0	-10000	0	0
GATA1	0.004	0.12	-10000	0	-0.59	20	20
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.029	0.005	-10000	0	-10000	0	0
NR3C1	0.022	0.03	-10000	0	-0.59	1	1
SUMO1/HDAC4	0.051	0.027	-10000	0	-10000	0	0
SRF	0.029	0.006	-10000	0	-10000	0	0
HDAC4/YWHAB	0.041	0.012	-10000	0	-10000	0	0
Tubulin	0.041	0.025	-10000	0	-0.47	1	1
HDAC4/14-3-3 E	0.041	0.011	-10000	0	-10000	0	0
GNB1	0.029	0.006	-10000	0	-10000	0	0
RANGAP1	0.03	0.004	-10000	0	-10000	0	0
BCL6/BCoR	0.042	0.011	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.043	0.028	-10000	0	-10000	0	0
HDAC4/SRF	0.045	0.033	-10000	0	-0.4	1	1
HDAC4/ER alpha	0.035	0.047	-10000	0	-0.46	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.032	0.044	-10000	0	-0.72	1	1
cell motility	0.055	0.026	-10000	0	-0.4	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.029	0.006	-10000	0	-10000	0	0
HDAC7/HDAC3	0.034	0.019	-10000	0	-10000	0	0
BCL6	0.029	0.007	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.028	0.007	-10000	0	-10000	0	0
Hsp90/HDAC6	0.041	0.012	-10000	0	-10000	0	0
ESR1	0.022	0.059	-10000	0	-0.56	5	5
HDAC6/HDAC11	0.03	0.03	-10000	0	-0.47	1	1
Ran/GTP/Exportin 1	0.052	0.029	-10000	0	-10000	0	0
NPC	0.017	0.003	-10000	0	-10000	0	0
MEF2C	0.026	0.01	-10000	0	-10000	0	0
RAN	0.029	0.006	-10000	0	-10000	0	0
HDAC4/MEF2C	0.062	0.041	-10000	0	-10000	0	0
GNG2	0.028	0.008	-10000	0	-10000	0	0
NCOR2	0.029	0.005	-10000	0	-10000	0	0
TUBB2A	0.028	0.03	-10000	0	-0.64	1	1
HDAC11	0.02	0.032	-10000	0	-0.64	1	1
HSP90AA1	0.028	0.008	-10000	0	-10000	0	0
RANBP2	0.029	0.005	-10000	0	-10000	0	0
ANKRA2	0.027	0.009	-10000	0	-10000	0	0
RFXANK	0.029	0.027	-10000	0	-0.59	1	1
nuclear import	-0.041	0.022	0.35	1	-10000	0	1

×

Circadian rhythm 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
chromatin modification	0.066	0.03	-10000	0	-10000	0	0
CLOCK	0.032	0.03	-10000	0	-0.63	1	1
TIMELESS/CRY2	0.056	0.027	-10000	0	-10000	0	0
DEC1/BMAL1	0.037	0.023	-10000	0	-0.43	1	1
ATR	0.028	0.007	-10000	0	-10000	0	0
NR1D1	0.035	0.064	-10000	0	-0.84	2	2
ARNTL	0.033	0.006	-10000	0	-10000	0	0
TIMELESS	0.038	0.024	-10000	0	-10000	0	0
NPAS2	0.024	0.071	-10000	0	-0.49	9	9
CRY2	0.03	0.003	-10000	0	-10000	0	0
mol:CO	-0.014	0.008	0.11	2	-10000	0	2
CHEK1	0.03	0.003	-10000	0	-10000	0	0
mol:HEME	0.014	0.008	-10000	0	-0.11	2	2
PER1	0.029	0.005	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.069	0.051	-10000	0	-0.39	4	4
BMAL1/CLOCK	0.05	0.06	-10000	0	-0.8	1	1
S phase of mitotic cell cycle	0.066	0.03	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.067	0.03	-10000	0	-10000	0	0
mol:NADPH	0.014	0.008	-10000	0	-0.11	2	2
PER1/TIMELESS	0.055	0.026	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.018	0.027	-10000	0	-0.59	1	1

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.049	0.06	-10000	0	-0.41	3	3
Ran/GTP/Exportin 1/HDAC1	0.008	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.055	-10000	0	-0.46	1	1
SUMO1	0.029	0.007	-10000	0	-10000	0	0
ZFPM1	0.025	0.05	-10000	0	-0.64	3	3
NPC/RanGAP1/SUMO1/Ubc9	0.022	0.008	-10000	0	-10000	0	0
FKBP3	0.028	0.008	-10000	0	-10000	0	0
Histones	0.056	0.045	-10000	0	-10000	0	0
YY1/LSF	0.009	0.067	-10000	0	-0.64	1	1
SMG5	0.029	0.007	-10000	0	-10000	0	0
RAN	0.029	0.006	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.026	0.034	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.03	0.039	-10000	0	-10000	0	0
SAP18	0.029	0.005	-10000	0	-10000	0	0
RELA	0.027	0.037	-10000	0	-10000	0	0
HDAC1/Smad7	0.052	0.022	-10000	0	-10000	0	0
RANGAP1	0.03	0.004	-10000	0	-10000	0	0
HDAC3/TR2	0.033	0.032	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.044	0.027	-10000	0	-0.32	1	1
NF kappa B1 p50/RelA	0.076	0.069	0.28	8	-0.55	1	9
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.014	0.096	-10000	0	-0.61	12	12
GATA1	0.004	0.12	-10000	0	-0.59	20	20
Mad/Max	0.04	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.049	0.055	-10000	0	-0.42	2	2
RBBP7	0.03	0.003	-10000	0	-10000	0	0
NPC	0.017	0.003	-10000	0	-10000	0	0
RBBP4	0.028	0.03	-10000	0	-0.64	1	1
MAX	0.028	0.008	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.023	0.013	-10000	0	-10000	0	0
NFKBIA	0.021	0.029	-10000	0	-10000	0	0
KAT2B	0.02	0.032	-10000	0	-0.64	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.035	0.045	-10000	0	-0.42	2	2
SIN3 complex	0.059	0.076	-10000	0	-0.33	18	18
SMURF1	0.027	0.009	-10000	0	-10000	0	0
CHD3	0.029	0.005	-10000	0	-10000	0	0
SAP30	0.008	0.11	-10000	0	-0.59	18	18
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.029	0.005	-10000	0	-10000	0	0
YY1/HDAC3	0.019	0.05	-10000	0	-0.56	1	1
YY1/HDAC2	0.012	0.064	-10000	0	-0.64	1	1
YY1/HDAC1	0.01	0.066	-10000	0	-0.64	1	1
NuRD/MBD2 Complex (MeCP1)	0.044	0.022	-10000	0	-10000	0	0
PPARG	0.021	0.041	-10000	0	-0.34	2	2
HDAC8/hEST1B	0.058	0.014	-10000	0	-10000	0	0
UBE2I	0.029	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.023	0.013	-10000	0	-10000	0	0
TNFRSF1A	0.029	0.006	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.033	0.032	-10000	0	-10000	0	0
MBD3L2	0.018	0.002	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.051	0.022	-10000	0	-10000	0	0
CREBBP	0.029	0.006	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.046	0.062	-10000	0	-0.37	1	1
HDAC1	0.029	0.006	-10000	0	-10000	0	0
HDAC3	0.023	0.027	-10000	0	-10000	0	0
HDAC2	0.028	0.008	-10000	0	-10000	0	0
YY1	0.021	0.036	-10000	0	-0.71	1	1
HDAC8	0.03	0.001	-10000	0	-10000	0	0
SMAD7	0.029	0.005	-10000	0	-10000	0	0
NCOR2	0.029	0.005	-10000	0	-10000	0	0
MXD1	0.029	0.005	-10000	0	-10000	0	0
STAT3	0.029	0.019	-10000	0	-0.36	1	1
NFKB1	0.028	0.029	-10000	0	-0.64	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.029	0.005	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.022	0.067	-10000	0	-0.6	1	1
YY1/SAP30/HDAC1	0.01	0.094	-10000	0	-0.47	5	5
EP300	0.028	0.029	-10000	0	-0.64	1	1
STAT3 (dimer non-phopshorylated)	0.029	0.019	-10000	0	-0.36	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.029	-10000	0	-10000	0	0
histone deacetylation	0.05	0.025	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.033	0.032	-10000	0	-10000	0	0
nuclear export	-0.057	0.014	-10000	0	-10000	0	0
PRKACA	0.03	0.002	-10000	0	-10000	0	0
GATAD2B	0.029	0.007	-10000	0	-10000	0	0
GATAD2A	0.03	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.026	0.06	-10000	0	-0.36	8	8
GATA1/HDAC1	0.023	0.091	-10000	0	-0.43	20	20
GATA1/HDAC3	0.022	0.066	-10000	0	-10000	0	0
CHD4	0.029	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.034	0.062	-10000	0	-0.45	8	8
SIN3/HDAC complex/Mad/Max	0.038	0.043	-10000	0	-0.41	2	2
NuRD Complex	0.051	0.06	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.053	0.043	-10000	0	-10000	0	0
SIN3B	0.03	0.003	-10000	0	-10000	0	0
MTA2	0.03	0.003	-10000	0	-10000	0	0
SIN3A	0.03	0.003	-10000	0	-10000	0	0
XPO1	0.029	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.051	0.027	-10000	0	-10000	0	0
HDAC complex	0.069	0.03	-10000	0	-10000	0	0
GATA1/Fog1	0.021	0.096	-10000	0	-0.44	21	21
FKBP25/HDAC1/HDAC2	0.052	0.021	-10000	0	-10000	0	0
TNF	0.019	0.079	-10000	0	-0.61	8	8
negative regulation of cell growth	0.04	0.043	-10000	0	-0.4	2	2
NuRD/MBD2/PRMT5 Complex	0.044	0.022	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.052	0.029	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.029	0.041	-10000	0	-0.34	2	2
SIN3/HDAC complex/NCoR1	0.038	0.041	-10000	0	-0.35	1	1
TFCP2	0.029	0.005	-10000	0	-10000	0	0
NR2C1	0.029	0.005	-10000	0	-10000	0	0
MBD3	0.027	0.04	-10000	0	-0.61	2	2
MBD2	0.029	0.005	-10000	0	-10000	0	0

×

Arf1 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
coatomer protein complex	0.052	0.074	0.31	9	-0.45	1	10
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.017	0.051	0.15	1	-0.28	9	10
AP2	0.042	0.01	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.037	0.014	-10000	0	-10000	0	0
CLTB	0.022	0.013	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0.014	-10000	0	-10000	0	0
CD4	0.018	0.081	-10000	0	-0.59	9	9
CLTA	0.029	0.006	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
ARFGAP1	0.011	0.021	-10000	0	-0.48	1	1
mol:PI-4-5-P2	0.011	0.016	-10000	0	-0.35	1	1
ARF1/GTP	0.035	0.013	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.016	0.021	-10000	0	-0.4	1	1
mol:Choline	0.011	0.016	-10000	0	-0.34	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.029	0.007	-10000	0	-10000	0	0
DDEF1	0.01	0.016	-10000	0	-0.35	1	1
ARF1/GDP	0.007	0.021	-10000	0	-0.39	1	1
AP2M1	0.029	0.006	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.017	0.007	-10000	0	-10000	0	0
Rac/GTP	0.021	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.042	0.022	-10000	0	-0.35	1	1
ARFIP2	0.027	0.008	-10000	0	-10000	0	0
COPA	0.029	0.007	-10000	0	-10000	0	0
RAC1	0.027	0.009	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.014	0.036	-10000	0	-0.29	4	4
ARF1/GTP/ARHGAP10	0.02	0.005	-10000	0	-10000	0	0
GGA3	0.029	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.028	0.029	-10000	0	-0.23	6	6
AP2A1	0.03	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.019	0.017	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.028	0.037	-10000	0	-0.3	6	6
Arfaptin 2/Rac/GDP	0.036	0.013	-10000	0	-10000	0	0
CYTH2	0.031	0.005	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.039	0.011	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.02	0.007	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.022	0.028	-10000	0	-10000	0	0
PLD2	0.011	0.016	-10000	0	-0.34	1	1
ARF-GAP1/v-SNARE	0.011	0.021	-10000	0	-0.47	1	1
PIP5K1A	0.011	0.016	-10000	0	-0.35	1	1
ARF1/GTP/Membrin/GBF1/p115	0.028	0.017	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.016	-10000	0	-0.34	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.011	0.021	-10000	0	-0.47	1	1
GOSR2	0.018	0.009	-10000	0	-10000	0	0
USO1	0.016	0.025	-10000	0	-0.3	3	3
GBF1	0.011	0.046	-10000	0	-0.3	11	11
ARF1/GTP/Arfaptin 2	0.041	0.011	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.049	0.058	-10000	0	-0.37	9	9

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.029	0.005	-10000	0	-10000	0	0
SMAD2	-0.027	0.066	0.23	1	-10000	0	1
SMAD3	0.027	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4	0.034	0.091	-10000	0	-0.47	11	11
SMAD4/Ubc9/PIASy	0.056	0.017	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.022	0.082	-10000	0	-10000	0	0
PPM1A	0.028	0.008	-10000	0	-10000	0	0
CALM1	0.028	0.008	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.016	0.076	-10000	0	-0.3	6	6
MAP3K1	0.027	0.009	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.042	0.015	-10000	0	-10000	0	0
MAPK3	0.029	0.006	-10000	0	-10000	0	0
MAPK1	0.03	0.004	-10000	0	-10000	0	0
NUP214	0.029	0.005	-10000	0	-10000	0	0
CTDSP1	0.028	0.007	-10000	0	-10000	0	0
CTDSP2	0.029	0.005	-10000	0	-10000	0	0
CTDSPL	0.021	0.014	-10000	0	-10000	0	0
KPNB1	0.029	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.028	0.016	-10000	0	-0.32	1	1
UBE2I	0.029	0.006	-10000	0	-10000	0	0
NUP153	0.029	0.006	-10000	0	-10000	0	0
KPNA2	0.029	0.005	-10000	0	-10000	0	0
PIAS4	0.03	0.003	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.015	0.1	-10000	0	-0.5	1	1
regulation of axonogenesis	-0.011	0.052	-10000	0	-10000	0	0
myoblast fusion	-0.018	0.061	0.35	3	-10000	0	3
mol:GTP	0.012	0.046	-10000	0	-0.39	1	1
regulation of calcium-dependent cell-cell adhesion	-0.047	0.054	0.34	1	-10000	0	1
ARF1/GTP	0.025	0.047	-10000	0	-0.3	1	1
mol:GM1	0.002	0.039	-10000	0	-0.31	1	1
mol:Choline	0.014	0.032	-10000	0	-10000	0	0
lamellipodium assembly	0.007	0.077	-10000	0	-0.46	2	2
MAPK3	0.022	0.056	-10000	0	-0.48	1	1
ARF6/GTP/NME1/Tiam1	0.048	0.054	-10000	0	-0.34	1	1
ARF1	0.029	0.006	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.061	-10000	0	-0.35	3	3
ARF1/GDP	0.017	0.074	-10000	0	-0.36	2	2
ARF6	0.028	0.027	-10000	0	-10000	0	0
RAB11A	0.03	0.003	-10000	0	-10000	0	0
TIAM1	0.03	0.009	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.054	-10000	0	-0.3	1	1
actin filament bundle formation	-0.01	0.073	0.36	2	-10000	0	2
KALRN	0.012	0.046	-10000	0	-0.35	1	1
RAB11FIP3/RAB11A	0.042	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.01	0.074	-10000	0	-0.36	2	2
NME1	0.029	0.028	-10000	0	-0.59	1	1
Rac1/GDP	0.023	0.069	-10000	0	-0.38	1	1
substrate adhesion-dependent cell spreading	0.012	0.046	-10000	0	-0.39	1	1
cortical actin cytoskeleton organization	0.006	0.077	-10000	0	-0.46	2	2
RAC1	0.027	0.009	-10000	0	-10000	0	0
liver development	0.012	0.046	-10000	0	-0.39	1	1
ARF6/GTP	0.012	0.046	-10000	0	-0.4	1	1
RhoA/GTP	0.017	0.044	-10000	0	-0.3	1	1
mol:GDP	0.003	0.069	-10000	0	-0.36	3	3
ARF6/GTP/RAB11FIP3/RAB11A	0.043	0.046	-10000	0	-10000	0	0
RHOA	0.021	0.014	-10000	0	-10000	0	0
PLD1	0.016	0.037	-10000	0	-10000	0	0
RAB11FIP3	0.029	0.006	-10000	0	-10000	0	0
tube morphogenesis	0.007	0.077	-10000	0	-0.46	2	2
ruffle organization	0.011	0.052	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.012	0.046	-10000	0	-0.39	1	1
PLD2	0.015	0.042	-10000	0	-0.28	1	1
PIP5K1A	0.011	0.052	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.014	0.032	-10000	0	-10000	0	0
Rac1/GTP	0.006	0.077	-10000	0	-0.47	2	2

×

TRAIL signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.027	0.03	-10000	0	-0.64	1	1
positive regulation of NF-kappaB transcription factor activity	0.037	0.027	-10000	0	-0.47	1	1
MAP2K4	0.037	0.031	-10000	0	-10000	0	0
IKBKB	0.028	0.008	-10000	0	-10000	0	0
TNFRSF10B	0.026	0.028	-10000	0	-0.59	1	1
TNFRSF10A	0.026	0.018	-10000	0	-0.32	1	1
SMPD1	0.019	0.014	-10000	0	-0.23	1	1
IKBKG	0.03	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.027	0.009	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.037	0.029	-10000	0	-0.47	1	1
TRAIL/TRAILR3	0.038	0.027	-10000	0	-0.47	1	1
TRAIL/TRAILR1	0.038	0.027	-10000	0	-0.47	1	1
TRAIL/TRAILR4	0.038	0.027	-10000	0	-0.47	1	1
TRAIL/TRAILR1/DAP3/GTP	0.047	0.029	-10000	0	-0.37	1	1
IKK complex	0.039	0.028	-10000	0	-10000	0	0
RIPK1	0.029	0.006	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.021	0.005	-10000	0	-10000	0	0
MAPK3	0.021	0.022	-10000	0	-0.47	1	1
MAP3K1	0.038	0.031	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.027	0.009	-10000	0	-10000	0	0
TRADD	0.029	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.026	0.018	-10000	0	-0.32	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.037	0.023	-10000	0	-10000	0	0
CFLAR	0.029	0.006	-10000	0	-10000	0	0
MAPK1	0.021	0.022	-10000	0	-0.47	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	0.072	0.039	-10000	0	-10000	0	0
mol:ceramide	0.019	0.014	-10000	0	-0.23	1	1
FADD	0.03	0.003	-10000	0	-10000	0	0
MAPK8	0.037	0.04	0.29	1	-10000	0	1
TRAF2	0.029	0.005	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.027	0.009	-10000	0	-10000	0	0
CHUK	0.029	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.052	0.029	-10000	0	-0.4	1	1
DAP3	0.028	0.007	-10000	0	-10000	0	0
CASP10	0.017	0.02	-10000	0	-0.4	1	1
JNK cascade	0.037	0.027	-10000	0	-0.47	1	1
TRAIL (trimer)	0.027	0.03	-10000	0	-0.63	1	1
TNFRSF10C	0.027	0.009	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.058	0.032	-10000	0	-0.35	1	1
TRAIL/TRAILR2/FADD	0.051	0.031	-10000	0	-0.4	1	1
cell death	0.019	0.014	-10000	0	-0.23	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.037	0.023	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.026	0.028	-10000	0	-0.59	1	1
CASP8	0.005	0.079	-10000	0	-0.58	9	9
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.072	0.04	-10000	0	-10000	0	0

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.029	0.006	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC4	0	0.001	-10000	0	-9999	0
MDM2/SUMO1	0.05	0.028	-10000	0	-9999	0
HDAC4	0.028	0.007	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC1	0	0.001	-10000	0	-9999	0
SUMO1	0.029	0.007	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	0.016	0.023	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	0.022	0.007	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	0.029	0.006	-10000	0	-9999	0
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	0.029	0.005	-10000	0	-9999	0
SUMO1/HDAC4	0.051	0.027	-10000	0	-9999	0
SUMO1/HDAC1	0.051	0.027	-10000	0	-9999	0
RANGAP1	0.03	0.004	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	0.07	0.023	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.022	0.008	-10000	0	-9999	0
Ran/GTP	0.037	0.028	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	0.029	0.005	-10000	0	-9999	0
UBE2I	0.029	0.006	-10000	0	-9999	0
Ran/GTP/Exportin 1	0.039	0.027	0.25	1	-9999	1
NPC	0.017	0.003	-10000	0	-9999	0
PIAS2	0.029	0.005	-10000	0	-9999	0
PIAS1	0.03	0.003	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.047	0.017	-9999	-10000	0	0
MAPK9	0.008	0.005	-9999	-10000	0	0
adrenocorticotropin secretion	-0.008	0.039	-9999	-0.44	4	4
GNB1/GNG2	0.036	0.012	-9999	-10000	0	0
GNB1	0.029	0.006	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.01	0.002	-9999	-10000	0	0
Gs family/GTP	0.019	0.003	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.029	0.005	-9999	-10000	0	0
GNG2	0.028	0.008	-9999	-10000	0	0
CRH	0.015	0.053	-9999	-0.59	4	4
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.009	0.024	-9999	-0.38	2	2
MAPK11	0.01	0.016	-9999	-0.26	2	2

×

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	0.039	0.042	-9999	-0.43	4	4
FBXW11	0.023	0.013	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.023	0.013	-9999	-10000	0	0
CHUK	0.029	0.006	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.062	0.048	-9999	-10000	0	0
NFKB1	0.028	0.029	-9999	-0.64	1	1
MAP3K14	0.025	0.054	-9999	-0.59	4	4
NF kappa B1 p50/RelB	0.042	0.024	-9999	-0.47	1	1
RELB	0.03	0.003	-9999	-10000	0	0
NFKB2	0.029	0.006	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.039	0.009	-9999	-10000	0	0
regulation of B cell activation	0.038	0.009	-9999	-10000	0	0

pid_entity	TCGA.T7.A92I	TCGA.MW.A4EC	TCGA.MM.A84U	TCGA.MM.A564
109_MAP3K5	0.054	0.1	-0.064	0.054
47_PPARGC1A	0.03	0.03	0.03	0.03
105_BMP4	0.03	0.03	0.03	0.03
105_BMP6	0.03	0.03	0.03	0.03
105_BMP7	0.03	0.018	-0.64	-0.64
105_BMP2	0.03	0.03	0.03	0.03
131_RELN/VLDLR	-0.35	-0.37	0.077	-0.37
30_TGFB1/TGF beta receptor Type II	0.03	0.029	0.029	0.034
84_STAT5B	-0.022	-0.052	-0.14	-0.14
84_STAT5A	-0.022	-0.052	-0.14	-0.14