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

Pathway.Name	Avg.Num.Perturbations
Class IB PI3K non-lipid kinase events	274
Signaling events mediated by Stem cell factor receptor (c-Kit)	269
Reelin signaling pathway	241
EGFR-dependent Endothelin signaling events	236
Signaling mediated by p38-alpha and p38-beta	203
HIF-1-alpha transcription factor network	190
p75(NTR)-mediated signaling	161
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	160
IL4-mediated signaling events	159
FOXA2 and FOXA3 transcription factor networks	144

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
Class IB PI3K non-lipid kinase events	0.2689	274	822	3	-0.22	-1000	1000	-1000	-0.019	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2640	269	21043	78	-0.62	0.19	1000	-1000	-0.071	-1000
Reelin signaling pathway	0.2365	241	13535	56	-0.48	0	1000	-1000	-0.075	-1000
EGFR-dependent Endothelin signaling events	0.2316	236	4961	21	-0.35	0	1000	-1000	-0.068	-1000
Signaling mediated by p38-alpha and p38-beta	0.1992	203	8936	44	-0.4	0	1000	-1000	-0.051	-1000
HIF-1-alpha transcription factor network	0.1865	190	14450	76	-0.76	0.019	1000	-1000	-0.083	-1000
p75(NTR)-mediated signaling	0.1580	161	20193	125	-0.39	0	1000	-1000	-0.095	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1570	160	10932	68	-0.54	0.19	1000	-1000	-0.089	-1000
IL4-mediated signaling events	0.1560	159	14498	91	-1	0.52	1000	-1000	-0.12	-1000
FOXA2 and FOXA3 transcription factor networks	0.1413	144	6661	46	-1.2	0.024	1000	-1000	-0.042	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1403	143	7754	54	-0.48	0.022	1000	-1000	-0.083	-1000
Glucocorticoid receptor regulatory network	0.1403	143	16322	114	-0.93	0.34	1000	-1000	-0.065	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1394	142	12533	88	-0.37	0.038	1000	-1000	-0.092	-1000
Aurora B signaling	0.1295	132	8893	67	-0.32	0.01	1000	-1000	-0.06	-1000
Arf6 signaling events	0.1237	126	7828	62	-0.35	0.017	1000	-1000	-0.06	-1000
Wnt signaling	0.1227	125	878	7	-0.17	-0.006	1000	-1000	-0.055	-1000
Endothelins	0.1217	124	11927	96	-0.38	0.035	1000	-1000	-0.077	-1000
Ephrin B reverse signaling	0.1197	122	5864	48	-0.33	0.19	1000	-1000	-0.067	-1000
FOXM1 transcription factor network	0.1178	120	6167	51	-0.43	0.014	1000	-1000	-0.13	-1000
EPHB forward signaling	0.1119	114	9695	85	-0.33	0.18	1000	-1000	-0.088	-1000
ErbB2/ErbB3 signaling events	0.1099	112	7289	65	-0.4	0.018	1000	-1000	-0.065	-1000
IGF1 pathway	0.1060	108	6194	57	-0.18	0.081	1000	-1000	-0.087	-1000
Calcium signaling in the CD4+ TCR pathway	0.0981	100	3112	31	-0.33	0.012	1000	-1000	-0.087	-1000
ErbB4 signaling events	0.0942	96	6642	69	-0.42	0.059	1000	-1000	-0.089	-1000
Nongenotropic Androgen signaling	0.0922	94	4904	52	-0.23	0.11	1000	-1000	-0.059	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0913	93	7935	85	-0.24	0.011	1000	-1000	-0.067	-1000
BMP receptor signaling	0.0913	93	7580	81	-0.55	0.026	1000	-1000	-0.085	-1000
Signaling events regulated by Ret tyrosine kinase	0.0913	93	7704	82	-0.17	0	1000	-1000	-0.083	-1000
Glypican 1 network	0.0893	91	4387	48	-0.32	0.031	1000	-1000	-0.053	-1000
IL23-mediated signaling events	0.0893	91	5487	60	-0.46	0.018	1000	-1000	-0.13	-1000
Noncanonical Wnt signaling pathway	0.0883	90	2365	26	-0.17	0	1000	-1000	-0.073	-1000
Plasma membrane estrogen receptor signaling	0.0873	89	7723	86	-0.2	0.09	1000	-1000	-0.072	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0873	89	10716	120	-0.6	0.24	1000	-1000	-0.078	-1000
Signaling events mediated by PTP1B	0.0854	87	6656	76	-0.65	0.074	1000	-1000	-0.07	-1000
Aurora C signaling	0.0834	85	601	7	-0.16	0	1000	-1000	-0.037	-1000
amb2 Integrin signaling	0.0824	84	6955	82	-0.5	0	1000	-1000	-0.074	-1000
Visual signal transduction: Rods	0.0805	82	4295	52	-0.48	0	1000	-1000	-0.077	-1000
Integrins in angiogenesis	0.0795	81	6805	84	-0.33	0	1000	-1000	-0.088	-1000
IL6-mediated signaling events	0.0756	77	5849	75	-0.28	0.051	1000	-1000	-0.08	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0726	74	3848	52	-0.19	0.03	1000	-1000	-0.053	-1000
Ephrin A reverse signaling	0.0716	73	516	7	-0.081	0	1000	-1000	-0.043	-1000
LPA receptor mediated events	0.0667	68	6956	102	-0.3	0.029	1000	-1000	-0.087	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0658	67	2298	34	-0.094	0	1000	-1000	-0.063	-1000
Syndecan-3-mediated signaling events	0.0658	67	2379	35	-0.35	0	1000	-1000	-0.065	-1000
Signaling events mediated by the Hedgehog family	0.0648	66	3439	52	-0.22	0.03	1000	-1000	-0.064	-1000
Syndecan-1-mediated signaling events	0.0628	64	2205	34	-0.22	0	1000	-1000	-0.063	-1000
PDGFR-alpha signaling pathway	0.0608	62	2737	44	-0.37	0.019	1000	-1000	-0.052	-1000
TCGA08_rtk_signaling	0.0608	62	1612	26	-0.3	0.026	1000	-1000	-0.035	-1000
Fc-epsilon receptor I signaling in mast cells	0.0589	60	5842	97	-0.24	0.028	1000	-1000	-0.085	-1000
S1P1 pathway	0.0589	60	2178	36	-0.33	0.008	1000	-1000	-0.066	-1000
E-cadherin signaling in keratinocytes	0.0589	60	2618	43	-0.3	0.04	1000	-1000	-0.067	-1000
Signaling events mediated by PRL	0.0579	59	2033	34	-0.18	0.021	1000	-1000	-0.059	-1000
Visual signal transduction: Cones	0.0520	53	2044	38	-0.17	0.008	1000	-1000	-0.063	-1000
Nectin adhesion pathway	0.0520	53	3366	63	-0.087	0.001	1000	-1000	-0.066	-1000
Presenilin action in Notch and Wnt signaling	0.0510	52	3185	61	-0.42	0.014	1000	-1000	-0.058	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0500	51	3779	74	-0.3	0.07	1000	-1000	-0.088	-1000
Rapid glucocorticoid signaling	0.0500	51	1024	20	-0.19	0.027	1000	-1000	-0.034	-1000
Signaling events mediated by HDAC Class III	0.0471	48	1945	40	-0.57	0.019	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0471	48	2287	47	-0.47	0.013	1000	-1000	-0.042	-1000
PLK1 signaling events	0.0461	47	4025	85	-0.22	0.031	1000	-1000	-0.053	-1000
Glypican 2 network	0.0461	47	190	4	-0.034	-0.029	1000	-1000	-0.032	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0461	47	1577	33	-0.55	0	1000	-1000	-0.063	-1000
LPA4-mediated signaling events	0.0442	45	546	12	-0.16	0.02	1000	-1000	-0.019	-1000
Canonical Wnt signaling pathway	0.0412	42	2182	51	-0.42	0.14	1000	-1000	-0.059	-1000
Syndecan-4-mediated signaling events	0.0402	41	2757	67	-0.32	0.004	1000	-1000	-0.073	-1000
IL27-mediated signaling events	0.0393	40	2044	51	-0.29	0.032	1000	-1000	-0.074	-1000
IL12-mediated signaling events	0.0363	37	3257	87	-0.35	0.049	1000	-1000	-0.11	-1000
Regulation of Telomerase	0.0363	37	3874	102	-0.35	0.022	1000	-1000	-0.084	-1000
Coregulation of Androgen receptor activity	0.0353	36	2774	76	-0.2	0.035	1000	-1000	-0.047	-1000
Regulation of Androgen receptor activity	0.0353	36	2568	70	-0.26	0.022	1000	-1000	-0.071	-1000
Ras signaling in the CD4+ TCR pathway	0.0353	36	623	17	-0.12	-0.001	1000	-1000	-0.063	-1000
TCR signaling in naïve CD8+ T cells	0.0343	35	3321	93	-0.16	0.077	1000	-1000	-0.075	-1000
Insulin Pathway	0.0334	34	2570	74	-0.2	0.033	1000	-1000	-0.084	-1000
Regulation of nuclear SMAD2/3 signaling	0.0324	33	4621	136	-0.31	0.052	1000	-1000	-0.065	-1000
Osteopontin-mediated events	0.0324	33	1259	38	-0.24	0.022	1000	-1000	-0.091	-1000
Regulation of p38-alpha and p38-beta	0.0314	32	1754	54	-0.37	0.029	1000	-1000	-0.067	-1000
Thromboxane A2 receptor signaling	0.0304	31	3320	105	-0.3	0.066	1000	-1000	-0.064	-1000
Syndecan-2-mediated signaling events	0.0304	31	2148	69	-0.2	0.034	1000	-1000	-0.053	-1000
IL2 signaling events mediated by STAT5	0.0304	31	695	22	-0.11	0.063	1000	-1000	-0.04	-1000
TCGA08_retinoblastoma	0.0304	31	255	8	-0.05	0.009	1000	-1000	-0.025	-1000
BCR signaling pathway	0.0304	31	3069	99	-0.13	0.043	1000	-1000	-0.082	-1000
Effects of Botulinum toxin	0.0285	29	771	26	-0.096	0.001	1000	-1000	-0.061	-1000
Aurora A signaling	0.0265	27	1628	60	-0.2	0.007	1000	-1000	-0.054	-1000
Arf6 trafficking events	0.0255	26	1903	71	-0.44	0.032	1000	-1000	-0.069	-1000
Hedgehog signaling events mediated by Gli proteins	0.0186	19	1267	65	-0.068	0.04	1000	-1000	-0.077	-1000
E-cadherin signaling events	0.0186	19	99	5	-0.025	0	1000	-1000	-0.043	-1000
Ceramide signaling pathway	0.0177	18	1419	76	-0.18	0.049	1000	-1000	-0.065	-1000
TRAIL signaling pathway	0.0177	18	902	48	-0.078	0.045	1000	-1000	-0.066	-1000
Class I PI3K signaling events mediated by Akt	0.0167	17	1202	68	-0.25	0.054	1000	-1000	-0.06	-1000
S1P5 pathway	0.0167	17	291	17	-0.039	0.023	1000	-1000	-0.047	-1000
Caspase cascade in apoptosis	0.0157	16	1212	74	-0.051	0.045	1000	-1000	-0.056	-1000
Cellular roles of Anthrax toxin	0.0157	16	638	39	-0.14	0.02	1000	-1000	-0.027	-1000
S1P4 pathway	0.0157	16	403	25	-0.039	0	1000	-1000	-0.052	-1000
Retinoic acid receptors-mediated signaling	0.0147	15	892	58	-0.1	0.038	1000	-1000	-0.063	-1000
IL2 signaling events mediated by PI3K	0.0137	14	831	58	-0.04	0.06	1000	-1000	-0.077	-1000
PLK2 and PLK4 events	0.0128	13	41	3	-0.011	0.014	1000	-1000	-0.024	-1000
IL1-mediated signaling events	0.0128	13	852	62	-0.038	0.032	1000	-1000	-0.087	-1000
Signaling mediated by p38-gamma and p38-delta	0.0128	13	206	15	-0.016	0.022	1000	-1000	-0.047	-1000
E-cadherin signaling in the nascent adherens junction	0.0118	12	969	76	-0.025	0.048	1000	-1000	-0.077	-1000
S1P3 pathway	0.0118	12	540	42	-0.028	0.022	1000	-1000	-0.052	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0108	11	312	28	-0.039	0.017	1000	-1000	-0.053	-1000
JNK signaling in the CD4+ TCR pathway	0.0108	11	197	17	-0.019	0.043	1000	-1000	-0.065	-1000
BARD1 signaling events	0.0098	10	589	57	-0.11	0.024	1000	-1000	-0.056	-1000
mTOR signaling pathway	0.0098	10	577	53	-0.02	0.025	1000	-1000	-0.058	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0088	9	362	37	-0.047	0.033	1000	-1000	-0.074	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0088	9	824	83	-0.039	0.051	1000	-1000	-0.077	-1000
p38 MAPK signaling pathway	0.0088	9	434	44	-0.071	0.026	1000	-1000	-0.062	-1000
Signaling events mediated by HDAC Class II	0.0079	8	662	75	-0.15	0	1000	-1000	-0.061	-1000
a4b1 and a4b7 Integrin signaling	0.0079	8	43	5	-0.009	-0.002	1000	-1000	-0.031	-1000
IFN-gamma pathway	0.0069	7	488	68	-0.071	0.075	1000	-1000	-0.085	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0069	7	327	45	-0.026	0.073	1000	-1000	-0.083	-1000
VEGFR1 specific signals	0.0069	7	426	56	-0.17	0.065	1000	-1000	-0.076	-1000
EPO signaling pathway	0.0059	6	373	55	-0.036	0.057	1000	-1000	-0.086	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0059	6	812	125	-0.17	0.083	1000	-1000	-0.098	-1000
Class I PI3K signaling events	0.0059	6	471	73	-0.041	0.059	1000	-1000	-0.06	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0049	5	136	23	-0.029	0.041	1000	-1000	-0.067	-1000
Atypical NF-kappaB pathway	0.0049	5	160	31	-0.02	0.03	1000	-1000	-0.069	-1000
PDGFR-beta signaling pathway	0.0049	5	559	97	-0.025	0.051	1000	-1000	-0.086	-1000
ceramide signaling pathway	0.0039	4	225	49	-0.028	0.053	1000	-1000	-0.049	-1000
HIF-2-alpha transcription factor network	0.0039	4	204	43	-0.18	0.18	1000	-1000	-0.077	-1000
Signaling events mediated by HDAC Class I	0.0039	4	483	104	-0.093	0.046	1000	-1000	-0.061	-1000
FoxO family signaling	0.0039	4	314	64	-0.04	0.093	1000	-1000	-0.072	-1000
Paxillin-dependent events mediated by a4b1	0.0029	3	121	36	-0.011	0.022	1000	-1000	-0.065	-1000
Canonical NF-kappaB pathway	0.0020	2	110	39	-0.021	0.077	1000	-1000	-0.076	-1000
Circadian rhythm pathway	0.0020	2	59	22	-0.014	0.042	1000	-1000	-0.075	-1000
Insulin-mediated glucose transport	0.0020	2	73	32	-0.13	0.032	1000	-1000	-0.062	-1000
Arf6 downstream pathway	0.0010	1	80	43	-0.011	0.021	1000	-1000	-0.036	-1000
TCGA08_p53	0.0000	0	0	7	-0.023	0.016	1000	-1000	-0.018	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	7	27	-0.001	0.029	1000	-1000	-0.05	-1000
Arf1 pathway	0.0000	0	23	54	-0.001	0.025	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	0.0000	0	1	13	-0.003	0	1000	-1000	-0.064	-1000
Total	NA	7569	448329	7203	-31	-990	131000	-131000	-8.6	-131000

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.22	0.35	0.8	274	-10000	0	274
PI3K Class IB/PDE3B	-0.22	0.36	-10000	0	-0.8	274	274
PDE3B	-0.22	0.36	-10000	0	-0.8	274	274

×

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

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.16	0.22	-10000	0	-0.39	464	464
CRKL	-0.17	0.23	-10000	0	-0.41	463	463
HRAS	-0.16	0.18	-10000	0	-0.53	34	34
mol:PIP3	-0.17	0.21	-10000	0	-0.4	466	466
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.18	0.24	-10000	0	-0.44	465	465
FOXO3	-0.15	0.21	-10000	0	-0.38	463	463
AKT1	-0.16	0.22	-10000	0	-0.41	464	464
BAD	-0.15	0.21	-10000	0	-0.37	463	463
megakaryocyte differentiation	-0.18	0.23	-10000	0	-0.43	465	465
GSK3B	-0.15	0.21	-10000	0	-0.37	463	463
RAF1	-0.092	0.17	-10000	0	-0.47	22	22
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	465	465
STAT1	-0.45	0.56	-10000	0	-1	475	475
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.44	27	27
cell proliferation	-0.18	0.24	-10000	0	-0.44	466	466
PIK3CA	0	0.009	-10000	0	-0.28	1	1
TEC	-0.002	0.043	-10000	0	-0.8	3	3
RPS6KB1	-0.18	0.24	-10000	0	-0.44	465	465
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.44	27	27
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	465	465
MAPK3	-0.054	0.13	-10000	0	-0.32	21	21
STAP1	-0.2	0.24	-10000	0	-0.45	467	467
GRAP2	-0.015	0.11	-10000	0	-0.8	18	18
JAK2	-0.4	0.44	-10000	0	-0.87	475	475
STAT1 (dimer)	-0.44	0.55	-10000	0	-1	475	475
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	465	465
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	465	465
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.33	-10000	0	-0.62	465	465
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.36	463	463
PI3K	-0.19	0.21	-10000	0	-0.41	469	469
PTEN	-0.002	0.035	-10000	0	-0.8	2	2
SCF/KIT/EPO/EPOR	-0.56	0.7	-10000	0	-1.3	463	463
MAPK8	-0.18	0.24	-10000	0	-0.45	466	466
STAT3 (dimer)	-0.18	0.23	-10000	0	-0.43	465	465
positive regulation of transcription	-0.042	0.11	-10000	0	-0.26	21	21
mol:GDP	-0.17	0.18	-10000	0	-0.57	34	34
PIK3C2B	-0.18	0.24	-10000	0	-0.44	465	465
CBL/CRKL	-0.17	0.19	-10000	0	-0.38	463	463
FER	-0.19	0.24	-10000	0	-0.44	471	471
SH2B3	-0.18	0.24	-10000	0	-0.44	465	465
PDPK1	-0.15	0.2	-10000	0	-0.36	465	465
SNAI2	-0.19	0.25	-10000	0	-0.45	467	467
positive regulation of cell proliferation	-0.32	0.41	-10000	0	-0.75	475	475
KITLG	0.001	0.07	-10000	0	-0.7	8	8
cell motility	-0.32	0.41	-10000	0	-0.75	475	475
PTPN6	0.015	0.021	-10000	0	-0.28	2	2
EPOR	-0.096	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	469	469
SOCS1	-0.005	0.042	-10000	0	-0.32	15	15
cell migration	0.19	0.24	0.44	473	-10000	0	473
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.044	0.11	-10000	0	-0.29	169	169
VAV1	-0.003	0.045	-10000	0	-0.8	3	3
GRB10	-0.18	0.24	-10000	0	-0.44	465	465
PTPN11	0.013	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.23	-10000	0	-0.47	465	465
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.064	0.14	-10000	0	-0.35	21	21
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.73	-10000	0	-1.4	461	461
MAP2K2	-0.064	0.14	-10000	0	-0.35	21	21
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	463	463
STAT5A	-0.27	0.35	-10000	0	-0.64	468	468
GRB2	0	0.009	-10000	0	-10000	0	0
response to radiation	-0.18	0.24	-10000	0	-0.44	467	467
SHC/GRAP2	-0.011	0.081	-10000	0	-0.61	18	18
PTPRO	-0.18	0.24	-10000	0	-0.44	465	465
SH2B2	-0.19	0.24	-10000	0	-0.44	465	465
DOK1	-0.001	0.018	-10000	0	-10000	0	0
MATK	-0.19	0.25	-10000	0	-0.45	473	473
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.13	0.31	-10000	0	-1.5	36	36

×

Reelin signaling pathway

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.006	0.033	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.8	31	31
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.8	2	2
ITGA3	-0.004	0.052	-9999	-0.58	7	7
RELN/VLDLR/Fyn	-0.33	0.28	-9999	-0.55	621	621
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.005	0.045	-9999	-0.45	10	10
AKT1	-0.2	0.17	-9999	-0.33	626	626
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.068	-9999	-0.29	61	61
RELN/LRP8/DAB1	-0.32	0.25	-9999	-0.51	614	614
LRPAP1/LRP8	-0.019	0.055	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.3	0.24	-9999	-0.48	614	614
DAB1/alpha3/beta1 Integrin	-0.28	0.22	-9999	-0.44	624	624
long-term memory	-0.36	0.3	-9999	-0.54	665	665
DAB1/LIS1	-0.29	0.23	-9999	-0.46	621	621
DAB1/CRLK/C3G	-0.28	0.22	-9999	-0.44	621	621
PIK3CA	0	0.009	-9999	-0.29	1	1
DAB1/NCK2	-0.29	0.23	-9999	-0.46	621	621
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.094	0.26	-9999	-0.8	115	115
CDK5R1	-0.008	0.048	-9999	-0.29	29	29
RELN	-0.48	0.39	-9999	-0.8	616	616
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
RELN/LRP8/Fyn	-0.33	0.27	-9999	-0.55	613	613
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.34	0.29	-9999	-0.55	633	633
MAPK8	-0.006	0.066	-9999	-0.8	7	7
RELN/VLDLR/DAB1	-0.32	0.26	-9999	-0.51	624	624
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.31	0.25	-9999	-0.5	624	624
RELN/LRP8	-0.33	0.26	-9999	-0.55	613	613
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.32	0.26	-9999	-0.5	649	649
PI3K	-0.006	0.061	-9999	-0.61	10	10
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.04	-9999	-0.61	4	4
RAP1A	-0.26	0.21	-9999	-0.47	251	251
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.048	-9999	-0.8	3	3
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.055	0.2	-9999	-0.79	71	71
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.13	0.11	-9999	-0.46	11	11
neuron adhesion	-0.24	0.2	-9999	-0.51	138	138
LRP8	-0.03	0.088	-9999	-0.29	107	107
GSK3B	-0.17	0.18	-9999	-0.45	66	66
RELN/VLDLR/DAB1/Fyn	-0.3	0.24	-9999	-0.48	621	621
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.22	0.18	-9999	-0.35	626	626
CDK5	-0.002	0.024	-9999	-10000	0	0
MAPT	-0.043	0.24	-9999	-0.73	108	108
neuron migration	-0.23	0.24	-9999	-0.42	615	615
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.11	-9999	-0.47	11	11
RELN/VLDLR	-0.32	0.26	-9999	-0.51	621	621

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	-0.002	0.025	-9999	-10000	0	0
EGFR	-0.3	0.39	-9999	-0.8	384	384
EGF/EGFR	-0.29	0.31	-9999	-0.55	534	534
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.26	0.28	-9999	-0.51	524	524
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.001	0.025	-9999	-0.8	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.8	214	214
EGF/EGFR dimer/SHC	-0.3	0.32	-9999	-0.59	524	524
mol:GDP	-0.26	0.27	-9999	-0.5	524	524
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.062	0.22	-9999	-0.8	80	80
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.24	0.25	-9999	-0.46	524	524
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.24	0.25	-9999	-0.47	524	524
FRAP1	-0.25	0.26	-9999	-0.48	524	524
EGF/EGFR dimer	-0.35	0.36	-9999	-0.68	524	524
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.048	0.16	-9999	-0.61	80	80

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.62	-9999	-1.3	345	345
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.082	0.15	-9999	-0.4	15	15
ATF2/c-Jun	-0.055	0.16	-9999	-0.84	16	16
MAPK11	-0.085	0.16	-9999	-0.49	18	18
MITF	-0.094	0.2	-9999	-0.36	352	352
MAPKAPK5	-0.09	0.19	-9999	-0.35	348	348
KRT8	-0.095	0.2	-9999	-0.36	349	349
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-10000	0	0
p38alpha-beta/CK2	-0.13	0.24	-9999	-0.45	348	348
CEBPB	-0.09	0.19	-9999	-0.35	348	348
SLC9A1	-0.09	0.19	-9999	-0.35	348	348
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.083	0.19	-9999	-0.34	349	349
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.55	18	18
JUN	-0.054	0.16	-9999	-0.82	16	16
PPARGC1A	-0.22	0.37	-9999	-0.58	429	429
USF1	-0.09	0.19	-9999	-0.35	348	348
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.39	15	15
NOS2	-0.093	0.22	-9999	-0.83	18	18
DDIT3	-0.09	0.19	-9999	-0.35	348	348
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.075	0.17	-9999	-0.43	51	51
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.55	18	18
CREB1	-0.094	0.2	-9999	-0.37	348	348
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.5	17	17
RPS6KA4	-0.09	0.19	-9999	-0.35	348	348
PLA2G4A	-0.13	0.27	-9999	-0.73	126	126
GDI1	-0.09	0.19	-9999	-0.35	348	348
TP53	-0.12	0.24	-9999	-0.44	348	348
RPS6KA5	-0.095	0.2	-9999	-0.36	356	356
ESR1	-0.17	0.25	-9999	-0.42	472	472
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.19	-9999	-0.36	348	348
MEF2A	-0.09	0.19	-9999	-0.36	348	348
EIF4EBP1	-0.094	0.2	-9999	-0.37	348	348
KRT19	-0.1	0.21	-9999	-0.38	351	351
ELK4	-0.09	0.19	-9999	-0.35	348	348
ATF6	-0.09	0.19	-9999	-0.35	348	348
ATF1	-0.094	0.2	-9999	-0.37	348	348
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.55	19	19
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.55	18	18

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.41	0.46	-9999	-1	263	263
HDAC7	0	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.32	0.31	-9999	-0.8	190	190
SMAD4	-0.001	0.025	-9999	-0.8	1	1
ID2	-0.41	0.46	-9999	-1	279	279
AP1	-0.19	0.29	-9999	-0.63	308	308
ABCG2	-0.43	0.5	-9999	-1.1	272	272
HIF1A	-0.051	0.063	-9999	-10000	0	0
TFF3	-0.48	0.52	-9999	-1.1	307	307
GATA2	-0.014	0.13	-9999	-0.77	29	29
AKT1	-0.052	0.08	-9999	-10000	0	0
response to hypoxia	-0.074	0.086	-9999	-0.24	38	38
MCL1	-0.41	0.46	-9999	-1	279	279
NDRG1	-0.41	0.46	-9999	-1	271	271
SERPINE1	-0.41	0.46	-9999	-1	279	279
FECH	-0.41	0.46	-9999	-1	246	246
FURIN	-0.41	0.46	-9999	-1	259	259
NCOA2	-0.025	0.16	-9999	-0.8	43	43
EP300	-0.052	0.12	-9999	-0.36	52	52
HMOX1	-0.41	0.46	-9999	-1	250	250
BHLHE40	-0.41	0.46	-9999	-1	269	269
BHLHE41	-0.42	0.47	-9999	-1	266	266
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.049	0.055	-9999	-0.61	1	1
ENG	-0.034	0.062	-9999	-0.55	1	1
JUN	-0.006	0.075	-9999	-0.8	9	9
RORA	-0.41	0.46	-9999	-1	265	265
ABCB1	-0.34	0.55	-9999	-1.4	199	199
TFRC	-0.41	0.46	-9999	-1	280	280
CXCR4	-0.41	0.46	-9999	-1	270	270
TF	-0.65	0.57	-9999	-1.1	505	505
CITED2	-0.41	0.46	-9999	-1	279	279
HIF1A/ARNT	-0.49	0.52	-9999	-1.2	283	283
LDHA	-0.048	0.047	-9999	-10000	0	0
ETS1	-0.41	0.46	-9999	-1	240	240
PGK1	-0.41	0.46	-9999	-0.99	280	280
NOS2	-0.41	0.46	-9999	-1	280	280
ITGB2	-0.41	0.46	-9999	-0.99	280	280
ALDOA	-0.41	0.46	-9999	-1	264	264
Cbp/p300/CITED2	-0.42	0.44	-9999	-1	251	251
FOS	-0.24	0.37	-9999	-0.8	307	307
HK2	-0.41	0.46	-9999	-1	262	262
SP1	0.012	0.023	-9999	-10000	0	0
GCK	-0.13	0.37	-9999	-1.6	55	55
HK1	-0.41	0.46	-9999	-1	262	262
NPM1	-0.41	0.46	-9999	-1	259	259
EGLN1	-0.41	0.46	-9999	-1	263	263
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.41	0.46	-9999	-1	279	279
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.19	0.41	-9999	-1.1	130	130
IGFBP1	-0.5	0.53	-9999	-1.1	337	337
VEGFA	-0.24	0.31	-9999	-0.76	103	103
HIF1A/JAB1	-0.028	0.025	-9999	-10000	0	0
CP	-0.52	0.55	-9999	-1.1	371	371
CXCL12	-0.44	0.5	-9999	-1.1	291	291
COPS5	0.008	0.006	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.019	-9999	-0.61	1	1
BNIP3	-0.41	0.46	-9999	-1	265	265
EGLN3	-0.42	0.46	-9999	-1	260	260
CA9	-0.45	0.48	-9999	-1.1	285	285
TERT	-0.42	0.47	-9999	-1	282	282
ENO1	-0.41	0.46	-9999	-1	259	259
PFKL	-0.41	0.46	-9999	-1	265	265
NCOA1	-0.001	0.025	-9999	-0.8	1	1
ADM	-0.44	0.49	-9999	-1.1	300	300
ARNT	-0.051	0.063	-9999	-10000	0	0
HNF4A	-0.001	0.041	-9999	-0.29	16	16
ADFP	-0.42	0.46	-9999	-1	283	283
SLC2A1	-0.24	0.32	-9999	-0.75	126	126
LEP	-0.76	0.52	-9999	-1.1	559	559
HIF1A/ARNT/Cbp/p300	-0.33	0.33	-9999	-0.8	224	224
EPO	-0.24	0.27	-9999	-0.85	43	43
CREBBP	-0.052	0.12	-9999	-0.36	52	52
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.31	-9999	-0.81	177	177
PFKFB3	-0.41	0.46	-9999	-1	265	265
NT5E	-0.41	0.46	-9999	-1	280	280

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.019	-9999	-0.61	1	1
Necdin/E2F1	-0.08	0.15	-9999	-0.69	39	39
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.15	0.22	-9999	-0.46	330	330
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.32	-9999	-0.63	405	405
NT-4/5 (dimer)/p75(NTR)	-0.39	0.42	-9999	-0.77	516	516
IKBKB	-0.001	0.013	-9999	-0.29	2	2
AKT1	-0.15	0.22	-9999	-0.46	333	333
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.07	0.22	-9999	-0.69	104	104
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.25	-9999	-0.56	321	321
FURIN	-0.001	0.013	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.21	0.29	-9999	-0.58	366	366
LINGO1	-0.068	0.12	-9999	-0.29	241	241
Sortilin/TRAF6/NRIF	-0.001	0.025	-9999	-0.79	1	1
proBDNF (dimer)	-0.07	0.22	-9999	-0.69	104	104
NTRK1	-0.01	0.067	-9999	-0.36	29	29
RTN4R	-0.011	0.055	-9999	-0.29	40	40
neuron apoptosis	-0.14	0.27	-9999	-0.5	327	327
IRAK1	-0.001	0.015	-9999	-0.29	3	3
SHC1	-0.16	0.27	-9999	-0.54	328	328
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.014	-9999	-0.45	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.16	0.23	-9999	-0.49	328	328
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.18	0.26	-9999	-0.53	342	342
Mammalian IAPs/DIABLO	-0.005	0.046	-9999	-0.48	9	9
proNGF (dimer)	-0.014	0.099	-9999	-0.64	22	22
MAGED1	-0.001	0.018	-9999	-0.29	4	4
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.28	0.38	-9999	-0.8	356	356
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.15	0.22	-9999	-0.46	328	328
NGF	-0.014	0.099	-9999	-0.64	22	22
cell cycle arrest	-0.12	0.23	-9999	-0.45	328	328
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.11	0.16	-9999	-0.33	328	328
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.34	0.37	-9999	-0.68	516	516
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.18	0.26	-9999	-0.55	328	328
PSENEN	0	0.009	-9999	-0.29	1	1
mol:ceramide	-0.14	0.25	-9999	-0.49	328	328
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.085	0.13	-9999	-0.48	13	13
p75(NTR)/beta APP	-0.19	0.28	-9999	-0.61	321	321
BEX1	-0.15	0.28	-9999	-0.8	138	138
mol:GDP	-0.16	0.27	-9999	-0.55	328	328
NGF (dimer)	-0.082	0.18	-9999	-0.5	158	158
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.23	-9999	-0.51	321	321
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
RAC1/GTP	-0.15	0.22	-9999	-0.47	328	328
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.18	0.26	-9999	-0.55	328	328
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.057	0.084	-9999	-10000	0	0
NT3 (dimer)	-0.13	0.29	-9999	-0.76	176	176
TP53	-0.17	0.24	-9999	-0.46	366	366
PRDM4	-0.14	0.25	-9999	-0.49	328	328
BDNF (dimer)	-0.17	0.23	-9999	-0.58	213	213
PIK3CA	0	0.009	-9999	-0.29	1	1
SORT1	-0.001	0.025	-9999	-0.8	1	1
activation of caspase activity	-0.15	0.22	-9999	-0.46	330	330
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.16	0.23	-9999	-0.49	328	328
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.16	0.27	-9999	-0.5	334	334
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.14	0.25	-9999	-0.49	328	328
APH1B	-0.001	0.025	-9999	-0.8	1	1
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.18	0.26	-9999	-0.54	328	328
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.29	0.36	-9999	-0.7	417	417
MAPK8	-0.11	0.24	-9999	-0.44	321	321
MAPK9	-0.11	0.24	-9999	-0.44	321	321
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.13	0.29	-9999	-0.76	176	176
NTF4	-0.28	0.38	-9999	-0.8	356	356
NDN	-0.031	0.15	-9999	-0.8	39	39
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.14	0.21	-9999	-0.43	328	328
p75 CTF/Sortilin/TRAF6/NRIF	0	0.015	-9999	-0.48	1	1
RhoA-B-C/GTP	-0.18	0.26	-9999	-0.55	328	328
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.18	0.25	-9999	-0.5	366	366
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.19	0.27	-9999	-0.53	366	366
PRKACB	-0.016	0.074	-9999	-0.32	51	51
proBDNF (dimer)/p75 ECD	-0.053	0.17	-9999	-0.61	81	81
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.08	-9999	-0.52	20	20
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.13	0.26	-9999	-0.47	328	328
BAD	-0.12	0.24	-9999	-0.45	323	323
RIPK2	-0.001	0.02	-9999	-10000	0	0
NGFR	-0.25	0.37	-9999	-0.8	321	321
CYCS	-0.15	0.22	-9999	-0.46	328	328
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.16	0.23	-9999	-0.49	328	328
BCL2L11	-0.12	0.24	-9999	-0.45	323	323
BDNF (dimer)/p75(NTR)	-0.24	0.33	-9999	-0.66	366	366
PI3K	-0.16	0.24	-9999	-0.5	333	333
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.16	0.23	-9999	-0.49	328	328
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0.009	-9999	-0.29	1	1
NGF (dimer)/p75(NTR)	-0.2	0.3	-9999	-0.62	328	328
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.16	0.23	-9999	-0.49	328	328
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.025	-9999	-0.8	1	1
PLG	-0.001	0.018	-9999	-0.29	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.2	0.27	-9999	-0.53	373	373
SQSTM1	0	0.009	-9999	-0.29	1	1
NGFRAP1	-0.002	0.036	-9999	-0.8	2	2
CASP3	-0.11	0.23	-9999	-0.42	323	323
E2F1	-0.09	0.13	-9999	-0.29	322	322
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.067	0.12	-9999	-0.58	20	20
NGF (dimer)/TRKA	-0.017	0.088	-9999	-0.61	19	19
MMP7	-0.12	0.28	-9999	-0.71	175	175
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.15	0.22	-9999	-0.46	328	328
MMP3	-0.12	0.16	-9999	-0.3	394	394
APAF-1/Caspase 9	-0.11	0.16	-9999	-0.66	15	15

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.074	0.15	-10000	0	-0.38	135	135
NFATC2	-0.061	0.27	-10000	0	-0.77	114	114
NFATC3	-0.06	0.13	-10000	0	-10000	0	0
CD40LG	-0.39	0.58	-10000	0	-1.1	336	336
ITCH	0.013	0.099	-10000	0	-10000	0	0
CBLB	0.013	0.099	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.26	0.36	-10000	0	-1.1	111	111
JUNB	-0.001	0.013	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.1	-10000	0	-0.34	108	108
T cell anergy	-0.028	0.16	-10000	0	-0.48	108	108
TLE4	-0.034	0.26	-10000	0	-0.74	90	90
Jun/NFAT1-c-4/p21SNFT	-0.33	0.46	-10000	0	-0.95	312	312
AP-1/NFAT1-c-4	-0.54	0.67	-10000	0	-1.4	345	345
IKZF1	-0.022	0.21	-10000	0	-0.59	101	101
T-helper 2 cell differentiation	-0.12	0.3	-10000	0	-0.77	129	129
AP-1/NFAT1	-0.23	0.33	-10000	0	-0.65	351	351
CALM1	-0.019	0.054	-10000	0	-10000	0	0
EGR2	-0.34	0.69	-10000	0	-1.3	291	291
EGR3	-0.43	0.76	-10000	0	-1.6	297	297
NFAT1/FOXP3	-0.12	0.22	-10000	0	-0.56	140	140
EGR1	-0.26	0.37	-10000	0	-0.8	325	325
JUN	-0.005	0.077	-10000	0	-0.81	9	9
EGR4	-0.02	0.073	-10000	0	-0.28	73	73
mol:Ca2+	-0.022	0.063	-10000	0	-10000	0	0
GBP3	-0.027	0.23	-10000	0	-0.62	108	108
FOSL1	-0.008	0.055	-10000	0	-0.33	25	25
NFAT1-c-4/MAF/IRF4	-0.34	0.49	-10000	0	-0.97	324	324
DGKA	-0.021	0.21	-10000	0	-0.58	101	101
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.42	0.54	-10000	0	-1.1	358	358
CTLA4	-0.089	0.24	-10000	0	-0.59	112	112
NFAT1-c-4 (dimer)/EGR1	-0.46	0.59	-10000	0	-1.2	357	357
NFAT1-c-4 (dimer)/EGR4	-0.32	0.47	-10000	0	-0.93	345	345
FOS	-0.24	0.38	-10000	0	-0.81	307	307
IFNG	-0.16	0.27	-10000	0	-0.84	105	105
T cell activation	-0.18	0.36	-10000	0	-0.79	201	201
MAF	-0.001	0.025	-10000	0	-0.8	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.19	0.38	0.72	278	-10000	0	278
TNF	-0.34	0.54	-10000	0	-1	334	334
FASLG	-0.4	0.71	-10000	0	-1.3	345	345
TBX21	-0.024	0.16	-10000	0	-0.68	54	54
BATF3	-0.002	0.029	-10000	0	-0.42	4	4
PRKCQ	-0.027	0.17	-10000	0	-0.71	56	56
PTPN1	-0.022	0.21	-10000	0	-0.59	100	100
NFAT1-c-4/ICER1	-0.32	0.46	-10000	0	-0.92	345	345
GATA3	-0.033	0.15	-10000	0	-0.57	61	61
T-helper 1 cell differentiation	-0.16	0.26	-10000	0	-0.82	105	105
IL2RA	-0.25	0.34	-10000	0	-0.97	118	118
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.021	0.21	-10000	0	-0.59	100	100
E2F1	-0.076	0.14	-10000	0	-0.28	322	322
PPARG	-0.19	0.34	-10000	0	-0.8	238	238
SLC3A2	-0.021	0.21	-10000	0	-0.58	101	101
IRF4	-0.073	0.23	-10000	0	-0.74	100	100
PTGS2	-0.49	0.66	-10000	0	-1.2	391	391
CSF2	-0.38	0.56	-10000	0	-1.1	335	335
JunB/Fra1/NFAT1-c-4	-0.31	0.45	-10000	0	-0.91	313	313
IL4	-0.13	0.32	-10000	0	-0.84	121	121
IL5	-0.38	0.56	-10000	0	-1.1	332	332
IL2	-0.19	0.36	-10000	0	-0.81	198	198
IL3	-0.066	0.066	-10000	0	-10000	0	0
RNF128	-0.052	0.28	-10000	0	-0.86	108	108
NFATC1	-0.19	0.38	-10000	0	-0.72	274	274
CDK4	0.099	0.24	0.63	31	-10000	0	31
PTPRK	-0.026	0.23	-10000	0	-0.61	111	111
IL8	-0.39	0.57	-10000	0	-1.1	337	337
POU2F1	0.001	0.01	-10000	0	-0.29	1	1

×

IL4-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
BCL2L1	-0.47	0.47	-10000	0	-1	307	307
STAT6 (cleaved dimer)	-0.51	0.45	-10000	0	-0.96	426	426
IGHG1	-0.16	0.16	-10000	0	-0.35	176	176
IGHG3	-0.46	0.45	-10000	0	-0.92	398	398
AKT1	-0.21	0.24	-10000	0	-0.58	159	159
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.2	-10000	0	-0.56	74	74
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.25	-10000	0	-0.55	223	223
THY1	-0.47	0.47	-10000	0	-1	308	308
MYB	-0.016	0.11	-10000	0	-0.75	21	21
HMGA1	-0.013	0.06	-10000	0	-0.29	47	47
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.3	-10000	0	-0.62	296	296
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.24	-10000	0	-0.54	159	159
SP1	0.018	0.004	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.024	0.03	-10000	0	-0.78	1	1
STAT6 (dimer)/ETS1	-0.49	0.44	-10000	0	-0.97	383	383
SOCS1	-0.3	0.31	-10000	0	-0.72	221	221
SOCS3	-0.23	0.26	-10000	0	-0.71	104	104
FCER2	-0.61	0.66	-10000	0	-1.4	374	374
PARP14	0.003	0.018	-10000	0	-0.29	3	3
CCL17	-0.48	0.47	-10000	0	-1.1	242	242
GRB2	0	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.53	46	46
T cell proliferation	-0.46	0.48	-10000	0	-1.1	315	315
IL4R/JAK1	-0.47	0.47	-10000	0	-1.1	266	266
EGR2	-0.62	0.65	-10000	0	-1.3	395	395
JAK2	-0.008	0.036	-10000	0	-0.82	1	1
JAK3	0.009	0.035	-10000	0	-0.28	14	14
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
JAK1	0.004	0.027	-10000	0	-0.8	1	1
COL1A2	-0.14	0.16	-10000	0	-1.7	2	2
CCL26	-0.47	0.47	-10000	0	-1.1	251	251
IL4R	-0.5	0.5	-10000	0	-1.1	299	299
PTPN6	0.022	0.018	-10000	0	-0.27	2	2
IL13RA2	-0.47	0.47	-10000	0	-1	308	308
IL13RA1	-0.007	0.026	-10000	0	-10000	0	0
IRF4	-0.23	0.48	-10000	0	-1.6	108	108
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.28	-10000	0	-0.62	247	247
GTF3A	0.013	0.016	-10000	0	-0.28	2	2
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL13RA1/JAK2	-0.014	0.042	-10000	0	-0.63	1	1
IRF4/BCL6	-0.2	0.43	-10000	0	-1.4	111	111
CD40LG	-0.033	0.18	-10000	0	-0.7	65	65
MAPK14	-0.26	0.28	-10000	0	-0.62	239	239
mitosis	-0.2	0.23	-10000	0	-0.55	159	159
STAT6	-0.53	0.55	-10000	0	-1.1	389	389
SPI1	0.007	0.022	-10000	0	-0.28	5	5
RPS6KB1	-0.19	0.23	-10000	0	-0.55	128	128
STAT6 (dimer)	-0.54	0.55	-10000	0	-1.1	384	384
STAT6 (dimer)/PARP14	-0.52	0.51	-10000	0	-1.1	393	393
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.24	-10000	0	-0.52	191	191
FRAP1	-0.21	0.24	-10000	0	-0.58	160	160
LTA	-0.48	0.47	-10000	0	-1.1	300	300
FES	-0.002	0.043	-10000	0	-0.8	3	3
T-helper 1 cell differentiation	0.52	0.53	1.1	391	-10000	0	391
CCL11	-0.49	0.45	-10000	0	-1	308	308
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.24	-10000	0	-0.54	169	169
IL2RG	-0.005	0.091	-10000	0	-0.36	52	52
IL10	-0.47	0.47	-10000	0	-1	307	307
IRS1	-0.034	0.16	-10000	0	-0.8	43	43
IRS2	-0.032	0.16	-10000	0	-0.8	41	41
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.47	-10000	0	-1.1	246	246
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.8	318	318
COL1A1	-0.18	0.17	-10000	0	-1.8	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.47	0.48	-10000	0	-1.2	241	241
IL2R gamma/JAK3	-0.013	0.072	-10000	0	-0.45	20	20
TFF3	-0.57	0.59	-10000	0	-1.3	315	315
ALOX15	-0.55	0.57	-10000	0	-1.3	307	307
MYBL1	-0.041	0.1	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.4	0.38	-10000	0	-0.82	364	364
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.008	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.24	-10000	0	-0.53	187	187
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.58	160	160
PI3K	-0.22	0.26	-10000	0	-0.61	160	160
DOK2	-0.003	0.04	-10000	0	-0.46	6	6
ETS1	0.019	0.056	-10000	0	-0.76	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.18	-10000	0	-0.53	36	36
ITGB3	-0.49	0.5	-10000	0	-1.2	272	272
PIGR	-1	0.75	-10000	0	-1.5	662	662
IGHE	0.046	0.04	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.52	36	36
BCL6	0.002	0.051	-10000	0	-0.8	4	4
OPRM1	-0.48	0.47	-10000	0	-1.1	298	298
RETNLB	-0.48	0.47	-10000	0	-1.1	255	255
SELP	-0.63	0.68	-10000	0	-1.5	323	323
AICDA	-0.46	0.45	-10000	0	-1.1	253	253

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.28	-9999	-0.82	84	84
PCK1	-1	0.7	-9999	-1.6	623	623
HNF4A	-0.24	0.28	-9999	-0.87	67	67
KCNJ11	-0.27	0.31	-9999	-0.89	107	107
AKT1	-0.14	0.14	-9999	-0.42	6	6
response to starvation	-0.001	0.007	-9999	-10000	0	0
DLK1	-0.49	0.56	-9999	-1.2	341	341
NKX2-1	-0.054	0.15	-9999	-0.54	2	2
ACADM	-0.24	0.28	-9999	-0.8	110	110
TAT	-1.2	0.68	-9999	-1.6	742	742
CEBPB	0.005	0.006	-9999	-10000	0	0
CEBPA	-0.002	0.076	-9999	-0.8	9	9
TTR	-0.45	0.28	-9999	-0.74	370	370
PKLR	-0.24	0.28	-9999	-0.8	99	99
APOA1	-0.29	0.3	-9999	-0.92	80	80
CPT1C	-0.24	0.28	-9999	-0.81	96	96
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.7	385	385
FOXF1	-0.004	0.056	-9999	-0.58	7	7
NF1	0.017	0.026	-9999	-0.8	1	1
HNF1A (dimer)	0.003	0.025	-9999	-0.28	7	7
CPT1A	-0.24	0.28	-9999	-0.82	87	87
HMGCS1	-0.24	0.28	-9999	-0.8	96	96
NR3C1	-0.11	0.13	-9999	-0.55	37	37
CPT1B	-0.24	0.28	-9999	-0.83	87	87
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.007	-9999	-10000	0	0
GCK	-0.28	0.35	-9999	-0.99	130	130
CREB1	-0.059	0.067	-9999	-10000	0	0
IGFBP1	-0.45	0.6	-9999	-1.5	232	232
PDX1	-0.13	0.14	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.84	77	77
ALDOB	-0.26	0.3	-9999	-0.84	113	113
AFP	-0.69	0.61	-9999	-1.3	430	430
BDH1	-0.24	0.28	-9999	-0.78	115	115
HADH	-0.26	0.3	-9999	-0.87	87	87
F2	-0.29	0.3	-9999	-0.89	91	91
HNF1A	0.003	0.025	-9999	-0.28	7	7
G6PC	-0.2	0.12	-9999	-0.67	6	6
SLC2A2	-0.16	0.17	-9999	-10000	0	0
INS	0.024	0.066	-9999	-10000	0	0
FOXA1	-0.25	0.28	-9999	-0.6	266	266
FOXA3	-0.43	0.23	-9999	-0.55	676	676
FOXA2	-0.32	0.34	-9999	-0.87	162	162
ABCC8	-0.34	0.43	-9999	-1.1	168	168
ALB	-0.94	0.64	-9999	-1.4	658	658

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.024	0.14	-9999	-0.8	31	31
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.33	0.26	-9999	-0.55	613	613
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-0.29	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.29	0.25	-9999	-0.49	613	613
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.068	-9999	-0.29	61	61
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.017	0.095	-9999	-0.43	40	40
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.009	-9999	-0.29	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.055	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.008	0.048	-9999	-0.29	29	29
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.043	0.1	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.34	0.28	-9999	-0.56	624	624
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.24	0.19	-9999	-0.45	174	174
MAP1B	-0.007	0.05	-9999	-0.38	18	18
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.26	0.21	-9999	-0.43	613	613
RELN	-0.48	0.39	-9999	-0.8	616	616
PAFAH/LIS1	-0.01	0.059	-9999	-0.53	11	11
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-9999	-0.41	23	23
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.21	0.17	-9999	-0.34	624	624
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.26	0.2	-9999	-0.42	613	613
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.033	0.092	-9999	-0.29	119	119
PAFAH1B2	-0.004	0.056	-9999	-0.8	5	5
MAP1B/LIS1/Dynein heavy chain	-0.004	0.032	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.22	0.18	-9999	-0.43	175	175
LRP8	-0.03	0.088	-9999	-0.29	107	107
NDEL1/Katanin 60	-0.24	0.19	-9999	-0.45	175	175
P39/CDK5	-0.28	0.22	-9999	-0.45	613	613
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.26	0.24	-9999	-0.46	613	613
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.29	0.24	-9999	-0.48	621	621
RELN/VLDLR	-0.32	0.26	-9999	-0.51	621	621
CDC42	0	0	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory 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
PCK2	0.023	0.078	0.31	37	-10000	0	37
SMARCC2	0.012	0.01	-10000	0	-10000	0	0
SMARCC1	0.012	0.01	-10000	0	-10000	0	0
TBX21	-0.14	0.26	-10000	0	-0.85	76	76
SUMO2	0	0.01	-10000	0	-0.29	1	1
STAT1 (dimer)	0.014	0.039	-10000	0	-0.35	1	1
FKBP4	-0.003	0.027	-10000	0	-10000	0	0
FKBP5	-0.012	0.092	-10000	0	-0.66	18	18
GR alpha/HSP90/FKBP51/HSP90	0.11	0.13	0.34	62	-0.41	16	78
PRL	-0.088	0.12	-10000	0	-0.51	3	3
cortisol/GR alpha (dimer)/TIF2	0.27	0.29	0.54	434	-0.57	25	459
RELA	-0.04	0.084	-10000	0	-0.3	1	1
FGG	0.24	0.22	0.5	274	-0.53	2	276
GR beta/TIF2	0.1	0.19	0.36	94	-0.58	45	139
IFNG	-0.42	0.35	-10000	0	-0.75	472	472
apoptosis	-0.28	0.3	0.59	3	-0.68	248	251
CREB1	-0.008	0.03	-10000	0	-10000	0	0
histone acetylation	0.022	0.14	0.42	35	-0.41	27	62
BGLAP	-0.1	0.15	-10000	0	-0.53	17	17
GR/PKAc	0.11	0.12	0.33	53	-0.47	4	57
NF kappa B1 p50/RelA	-0.066	0.15	-10000	0	-0.44	27	27
SMARCD1	0.012	0.01	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.26	228	-10000	0	228
GATA3	-0.024	0.15	-10000	0	-0.64	49	49
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.04	0.11	0.39	1	-0.6	8	9
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.26	0.56	3	-0.64	136	139
CSN2	0.2	0.18	0.42	206	-0.54	1	207
BRG1/BAF155/BAF170/BAF60A	-0.003	0.033	-10000	0	-0.46	5	5
NFATC1	0	0.044	-10000	0	-0.8	3	3
POU2F1	0.007	0.013	-10000	0	-0.29	1	1
CDKN1A	0.046	0.074	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.008	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.8	13	13
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.34	51	-0.42	11	62
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.37	0.43	0.54	3	-0.91	356	359
JUN	-0.32	0.29	-10000	0	-0.59	454	454
IL4	-0.13	0.16	-10000	0	-0.48	59	59
CDK5R1	-0.008	0.049	-10000	0	-0.29	29	29
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.42	0.41	-10000	0	-0.74	556	556
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.34	54	-0.4	8	62
cortisol/GR alpha (monomer)	0.34	0.32	0.63	479	-0.56	2	481
NCOA2	-0.034	0.16	-10000	0	-0.8	43	43
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.29	0.39	-10000	0	-0.87	307	307
AP-1/NFAT1-c-4	-0.66	0.52	-10000	0	-1	643	643
AFP	-0.61	0.7	-10000	0	-1.6	341	341
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.49	71	-10000	0	71
TP53	0.031	0.024	-10000	0	-0.5	2	2
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.83	0.8	-10000	0	-1.5	516	516
KRT14	-0.83	0.77	-10000	0	-1.6	538	538
TBP	0.019	0.005	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.28	434	-10000	0	434
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.67	0.53	-10000	0	-1	643	643
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.13	0.29	-10000	0	-0.81	159	159
MAPK11	-0.002	0.044	-10000	0	-0.81	3	3
KRT5	-0.93	0.82	-10000	0	-1.7	550	550
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.011	0.026	-10000	0	-0.8	1	1
STAT1	0.014	0.039	-10000	0	-0.35	1	1
CGA	-0.16	0.18	-10000	0	-0.54	58	58
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.18	0.37	497	-10000	0	497
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.18	0.25	-10000	0	-0.58	198	198
NFKB1	-0.04	0.084	-10000	0	-10000	0	0
MAPK8	-0.24	0.22	-10000	0	-0.48	323	323
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.29	0.31	0.59	3	-0.72	248	251
BAX	0.048	0.032	-10000	0	-10000	0	0
POMC	-0.18	0.3	-10000	0	-0.97	75	75
EP300	0.14	0.14	0.29	334	-10000	0	334
cortisol/GR alpha (dimer)/p53	0.31	0.26	0.55	457	-0.57	1	458
proteasomal ubiquitin-dependent protein catabolic process	0.086	0.08	0.24	55	-10000	0	55
SGK1	0.22	0.2	-10000	0	-1.2	6	6
IL13	-0.31	0.28	-10000	0	-0.64	302	302
IL6	-0.5	0.63	-10000	0	-1.3	379	379
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.27	0.22	-10000	0	-0.71	71	71
IL2	-0.41	0.35	-10000	0	-0.75	464	464
CDK5	-0.002	0.024	-10000	0	-0.29	5	5
PRKACB	-0.016	0.074	-10000	0	-0.32	51	51
HSP90AA1	0	0.009	-10000	0	-10000	0	0
IL8	-0.2	0.31	-10000	0	-0.66	205	205
CDK5R1/CDK5	-0.007	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.057	0.099	-10000	0	-0.54	6	6
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.53	392	-0.5	2	394
SMARCA4	0.012	0.014	-10000	0	-0.28	1	1
chromatin remodeling	0.2	0.16	0.4	242	-10000	0	242
NF kappa B1 p50/RelA/Cbp	0.06	0.17	0.34	63	-0.49	1	64
JUN (dimer)	-0.32	0.29	-10000	0	-0.59	455	455
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.13	0.25	-10000	0	-0.75	94	94
NR3C1	0.2	0.21	0.46	256	-0.55	7	263
NR4A1	-0.054	0.23	-10000	0	-0.75	93	93
TIF2/SUV420H1	-0.026	0.12	-10000	0	-0.61	43	43
MAPKKK cascade	-0.28	0.3	0.59	3	-0.68	248	251
cortisol/GR alpha (dimer)/Src-1	0.3	0.26	0.55	447	-0.58	1	448
PBX1	0.005	0.039	-10000	0	-0.54	4	4
POU1F1	0.003	0.015	-10000	0	-10000	0	0
SELE	-0.23	0.37	-10000	0	-0.89	158	158
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.4	236	-10000	0	236
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.53	392	-0.5	2	394
mol:cortisol	0.2	0.2	0.36	499	-10000	0	499
MMP1	-0.21	0.11	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.12	0.41	-10000	0	-0.9	214	214
NCK1/PAK1/Dok-R	-0.089	0.17	-10000	0	-0.42	214	214
NCK1/Dok-R	-0.24	0.47	-10000	0	-1.1	214	214
PIK3CA	0.003	0.011	-10000	0	-0.29	1	1
mol:beta2-estradiol	0.036	0.099	0.24	179	-10000	0	179
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.003	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.038	0.1	0.25	179	-0.31	7	186
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.22	0.43	-10000	0	-1.1	214	214
FN1	-0.11	0.14	-10000	0	-0.29	404	404
PLD2	-0.19	0.52	-10000	0	-1.2	214	214
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.22	-10000	0	-0.8	77	77
ELK1	-0.15	0.46	-10000	0	-1	214	214
GRB7	-0.02	0.076	-10000	0	-0.8	1	1
PAK1	-0.006	0.042	-10000	0	-0.29	23	23
Tie2/Ang1/alpha5/beta1 Integrin	-0.19	0.48	-10000	0	-1.1	214	214
CDKN1A	-0.061	0.28	-10000	0	-0.6	172	172
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.24	0.47	-10000	0	-1.1	214	214
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.065	0.31	-10000	0	-0.66	214	214
PLG	-0.2	0.52	-10000	0	-1.2	214	214
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.18	0.37	-10000	0	-0.88	214	214
GRB2	0	0.009	-10000	0	-10000	0	0
PIK3R1	-0.003	0.08	-10000	0	-0.81	10	10
ANGPT2	-0.11	0.27	-10000	0	-0.68	129	129
BMX	-0.37	0.58	-10000	0	-1.4	216	216
ANGPT1	-0.23	0.57	-10000	0	-1.4	190	190
tube development	-0.077	0.3	-10000	0	-0.64	214	214
ANGPT4	-0.24	0.37	-10000	0	-0.8	307	307
response to hypoxia	-0.01	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.28	0.54	-10000	0	-1.3	214	214
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.32	0.39	-10000	0	-0.8	409	409
STAT5A (dimer)	-0.094	0.35	-10000	0	-0.77	180	180
mol:L-citrulline	-0.065	0.31	-10000	0	-0.66	214	214
AGTR1	-0.2	0.34	-10000	0	-0.7	300	300
MAPK14	-0.18	0.5	-10000	0	-1.1	214	214
Tie2/SHP2	-0.094	0.28	-10000	0	-1.3	45	45
TEK	-0.098	0.31	-10000	0	-1.5	45	45
RPS6KB1	-0.11	0.4	-10000	0	-0.87	214	214
Angiotensin II/AT1	-0.16	0.26	-10000	0	-0.62	241	241
Tie2/Ang1/GRB2	-0.26	0.51	-10000	0	-1.2	214	214
MAPK3	-0.16	0.47	-10000	0	-1.1	214	214
MAPK1	-0.16	0.47	-10000	0	-1.1	214	214
Tie2/Ang1/GRB7	-0.25	0.52	-10000	0	-1.2	214	214
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.19	0.52	-10000	0	-1.2	214	214
PI3K	-0.15	0.47	-10000	0	-1.1	214	214
FES	-0.18	0.5	-10000	0	-1.1	214	214
Crk/Dok-R	-0.24	0.47	-10000	0	-1.1	214	214
Tie2/Ang1/ABIN2	-0.26	0.51	-10000	0	-1.2	214	214
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.097	0.37	-10000	0	-0.8	214	214
STAT5A	-0.006	0.071	-10000	0	-0.8	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.11	0.4	-10000	0	-0.87	214	214
Tie2/Ang2	-0.13	0.41	-10000	0	-0.87	213	213
Tie2/Ang1	-0.22	0.57	-10000	0	-1.3	214	214
FOXO1	-0.094	0.38	-10000	0	-0.81	215	215
ELF1	0.014	0.022	-10000	0	-10000	0	0
ELF2	-0.19	0.51	-10000	0	-1.2	214	214
mol:Choline	-0.18	0.49	-10000	0	-1.1	214	214
cell migration	-0.039	0.1	-10000	0	-0.24	201	201
FYN	-0.095	0.34	-10000	0	-0.73	213	213
DOK2	-0.003	0.04	-10000	0	-0.46	6	6
negative regulation of cell cycle	-0.051	0.25	-10000	0	-0.54	174	174
ETS1	-0.027	0.11	-10000	0	-0.97	5	5
PXN	-0.076	0.33	-10000	0	-0.71	214	214
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.083	0.35	-10000	0	-0.75	214	214
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.04	0.14	-10000	0	-0.53	36	36
MAPKKK cascade	-0.18	0.49	-10000	0	-1.1	214	214
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.24	0.52	-10000	0	-1.2	214	214
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.052	0.28	-10000	0	-0.59	214	214
mol:Phosphatidic acid	-0.18	0.49	-10000	0	-1.1	214	214
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.065	0.31	-10000	0	-0.66	214	214
Rac1/GTP	-0.17	0.33	-10000	0	-0.81	214	214
MMP2	-0.19	0.52	-10000	0	-1.2	215	215

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.05	0.063	-9999	-10000	0	0
STMN1	-0.1	0.12	-9999	-0.36	77	77
Aurora B/RasGAP/Survivin	-0.18	0.13	-9999	-0.29	133	133
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.15	-9999	-0.33	411	411
BIRC5	-0.2	0.13	-9999	-0.29	732	732
DES	-0.29	0.34	-9999	-0.65	467	467
Aurora C/Aurora B/INCENP	-0.066	0.074	-9999	-0.62	1	1
Aurora B/TACC1	-0.098	0.13	-9999	-0.62	39	39
Aurora B/PP2A	-0.096	0.094	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.007	0.016	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.21	0.17	-9999	-0.36	523	523
Cul3 protein complex	-0.21	0.26	-9999	-0.53	411	411
KIF2C	-0.04	0.03	-9999	-10000	0	0
PEBP1	0.002	0.005	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-0.29	768	768
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.096	0.094	-9999	-10000	0	0
SEPT1	-0.008	0.048	-9999	-0.29	30	30
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.004	0.033	-9999	-0.29	14	14
NSUN2/NPM1/Nucleolin	0.01	0.017	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.002	-9999	-10000	0	0
H3F3B	-0.034	0.041	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-0.29	586	586
AURKC	-0.004	0.041	-9999	-0.32	14	14
CDCA8	-0.096	0.14	-9999	-0.29	346	346
cytokinesis	-0.11	0.072	-9999	-10000	0	0
Aurora B/Septin1	-0.09	0.083	-9999	-10000	0	0
AURKA	-0.14	0.15	-9999	-0.29	479	479
INCENP	0.003	0.005	-9999	-10000	0	0
KLHL13	-0.32	0.39	-9999	-0.8	410	410
BUB1	-0.2	0.14	-9999	-0.29	698	698
hSgo1/Aurora B/Survivin	-0.25	0.17	-9999	-0.37	636	636
EVI5	0.008	0.005	-9999	-10000	0	0
RhoA/GTP	-0.095	0.095	-9999	-0.33	14	14
SGOL1	-0.18	0.14	-9999	-0.29	653	653
CENPA	-0.053	0.058	-9999	-10000	0	0
NCAPG	-0.14	0.14	-9999	-0.29	512	512
Aurora B/HC8 Proteasome	-0.096	0.094	-9999	-10000	0	0
NCAPD2	-0.002	0.025	-9999	-0.29	8	8
Aurora B/PP1-gamma	-0.096	0.094	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.11	0.14	-9999	-0.29	404	404
NPM1	-0.015	0.022	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.002	0.036	-9999	-0.8	2	2
mitotic prometaphase	-0.006	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.096	0.094	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.11	0.1	-9999	-0.35	34	34
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.015	0.022	-9999	-10000	0	0
MYLK	-0.086	0.15	-9999	-0.47	126	126
KIF23	-0.088	0.13	-9999	-10000	0	0
VIM	-0.092	0.1	-9999	-0.69	2	2
RACGAP1	-0.01	0.058	-9999	-0.29	41	41
mitosis	0	0	-9999	-10000	0	0
NCL	-0.015	0.022	-9999	-10000	0	0
Chromosomal passenger complex	-0.077	0.073	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.16	0.17	-9999	-0.35	283	283
TACC1	-0.031	0.15	-9999	-0.8	39	39
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.045	-9999	-0.66	4	4
ARNO/beta Arrestin1-2	-0.13	0.19	-9999	-0.44	241	241
EGFR	-0.3	0.39	-9999	-0.8	384	384
EPHA2	-0.005	0.061	-9999	-0.8	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.35	0.36	-9999	-0.68	524	524
ARRB2	-0.054	0.16	-9999	-0.44	141	141
mol:GTP	0.017	0.018	-9999	-0.15	5	5
ARRB1	-0.002	0.037	-9999	-0.63	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.037	0.17	-9999	-0.75	50	50
EGF	-0.17	0.33	-9999	-0.8	214	214
somatostatin receptor activity	0	0	-9999	-0.001	326	326
ARAP2	-0.004	0.056	-9999	-0.8	5	5
mol:GDP	-0.14	0.18	-9999	-0.35	320	320
mol:PI-3-4-5-P3	0	0	-9999	-0.001	213	213
ITGA2B	-0.018	0.077	-9999	-0.31	57	57
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.038	-9999	-0.48	6	6
ADAP1	-0.005	0.05	-9999	-0.43	11	11
KIF13B	-0.002	0.036	-9999	-0.8	2	2
HGF/MET	-0.14	0.28	-9999	-0.66	217	217
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.32	321	321
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.3	0.32	-9999	-0.59	524	524
ADRB2	-0.19	0.34	-9999	-0.8	241	241
receptor agonist activity	0	0	-9999	0	324	324
actin filament binding	0	0	-9999	-0.001	311	311
SRC	0	0.009	-9999	-0.29	1	1
ITGB3	-0.029	0.15	-9999	-0.75	39	39
GNAQ	-0.002	0.036	-9999	-0.8	2	2
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	301	301
ARF6/GDP	-0.015	0.084	-9999	-0.42	17	17
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.52	169	169
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.025	0.096	-9999	-0.49	38	38
ACAP1	-0.019	0.095	-9999	-0.39	48	48
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.092	0.23	-9999	-0.66	141	141
EFNA1	0	0	-9999	-10000	0	0
HGF	-0.053	0.2	-9999	-0.8	67	67
CYTH3	0.01	0.02	-9999	-0.62	1	1
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	266	266
endosomal lumen acidification	0	0	-9999	-0.001	271	271
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.052	0.2	-9999	-0.8	66	66
GNAQ/ARNO	0.004	0.022	-9999	-0.46	2	2
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	329	329
MET	-0.13	0.3	-9999	-0.8	171	171
GNA14	-0.014	0.088	-9999	-0.45	31	31
GNA15	-0.003	0.034	-9999	-0.35	8	8
GIT1	-0.001	0.02	-9999	-0.29	5	5
mol:PI-4-5-P2	0	0	-9999	-0.001	318	318
GNA11	-0.002	0.036	-9999	-0.8	2	2
LHCGR	-0.11	0.28	-9999	-0.8	141	141
AGTR1	-0.21	0.34	-9999	-0.8	241	241
desensitization of G-protein coupled receptor protein signaling pathway	-0.091	0.23	-9999	-0.66	141	141
IPCEF1/ARNO	-0.24	0.25	-9999	-0.47	524	524
alphaIIb/beta3 Integrin	-0.033	0.12	-9999	-0.63	38	38

×

Wnt 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
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	361	361
FZD6	-0.006	0.071	-9999	-0.8	8	8
WNT6	-0.17	0.32	-9999	-0.71	241	241
WNT4	-0.021	0.12	-9999	-0.8	20	20
FZD3	-0.009	0.083	-9999	-0.8	11	11
WNT5A	-0.015	0.1	-9999	-0.6	25	25
WNT11	-0.17	0.32	-9999	-0.8	212	212

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.012	0.2	-9999	-0.6	84	84
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.019	0.2	-9999	-0.98	30	30
EDN1	-0.039	0.24	-9999	-0.82	83	83
EDN3	-0.38	0.4	-9999	-0.8	479	479
EDN2	-0.073	0.14	-9999	-0.3	249	249
HRAS/GDP	-0.03	0.21	-9999	-0.55	87	87
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.14	-9999	-0.48	43	43
ADCY4	-0.15	0.29	-9999	-0.56	293	293
ADCY5	-0.28	0.36	-9999	-0.61	482	482
ADCY6	-0.14	0.27	-9999	-0.54	278	278
ADCY7	-0.14	0.27	-9999	-0.54	278	278
ADCY1	-0.15	0.29	-9999	-0.56	292	292
ADCY2	-0.17	0.32	-9999	-0.6	305	305
ADCY3	-0.14	0.27	-9999	-0.54	278	278
ADCY8	-0.14	0.27	-9999	-0.54	278	278
ADCY9	-0.14	0.27	-9999	-0.54	278	278
arachidonic acid secretion	-0.1	0.3	-9999	-0.61	177	177
ETB receptor/Endothelin-1/Gq/GTP	-0.033	0.18	-9999	-0.4	146	146
GNAO1	-0.031	0.14	-9999	-0.48	66	66
HRAS	-0.002	0.025	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.035	0.21	-9999	-0.56	84	84
ETA receptor/Endothelin-1/Gs/GTP	-0.095	0.32	-9999	-0.57	278	278
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.021	0.21	-9999	-0.6	84	84
EDNRB	-0.07	0.24	-9999	-0.8	99	99
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.027	0.24	-9999	-0.69	100	100
CYSLTR1	-0.023	0.23	-9999	-0.67	96	96
SLC9A1	0.001	0.1	-9999	-0.3	84	84
mol:GDP	-0.039	0.22	-9999	-0.57	98	98
SLC9A3	-0.052	0.28	-9999	-0.64	168	168
RAF1	-0.085	0.25	-9999	-0.56	147	147
JUN	0.024	0.19	-9999	-0.88	29	29
JAK2	-0.013	0.2	-9999	-0.6	84	84
mol:IP3	-0.029	0.18	-9999	-0.53	67	67
ETA receptor/Endothelin-1	0.032	0.25	-9999	-0.64	97	97
PLCB1	-0.052	0.21	-9999	-0.8	74	74
PLCB2	0.006	0.028	-9999	-0.54	2	2
ETA receptor/Endothelin-3	-0.28	0.32	-9999	-0.61	478	478
FOS	-0.26	0.5	-9999	-0.99	314	314
Gai/GDP	-0.016	0.16	-9999	-0.78	28	28
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	-0.051	0.25	-9999	-0.67	110	110
BCAR1	0.002	0.004	-9999	-10000	0	0
PRKCB1	-0.032	0.17	-9999	-0.48	82	82
GNAQ	0.008	0.037	-9999	-0.81	2	2
GNAZ	-0.007	0.075	-9999	-0.8	9	9
GNAL	-0.19	0.34	-9999	-0.8	244	244
Gs family/GDP	-0.18	0.26	-9999	-0.54	290	290
ETA receptor/Endothelin-1/Gq/GTP	0.016	0.13	-9999	-0.4	53	53
MAPK14	-0.031	0.17	-9999	-0.49	80	80
TRPC6	0.016	0.22	-9999	-1.1	30	30
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.039	0.17	-9999	-0.8	49	49
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.04	0.18	-9999	-0.46	110	110
ETB receptor/Endothelin-2	-0.1	0.2	-9999	-0.66	105	105
ETB receptor/Endothelin-3	-0.34	0.34	-9999	-0.66	530	530
ETB receptor/Endothelin-1	-0.082	0.27	-9999	-0.67	168	168
MAPK3	-0.2	0.41	-9999	-0.79	317	317
MAPK1	-0.2	0.41	-9999	-0.79	317	317
Rac1/GDP	-0.029	0.2	-9999	-0.55	87	87
cAMP biosynthetic process	-0.18	0.3	-9999	-0.59	299	299
MAPK8	0.017	0.19	-9999	-0.76	37	37
SRC	0	0.009	-9999	-0.28	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.047	0.18	-9999	-0.48	103	103
p130Cas/CRK/Src/PYK2	-0.016	0.22	-9999	-0.64	68	68
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.029	0.2	-9999	-0.53	95	95
COL1A2	-0.056	0.25	-9999	-0.68	98	98
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.028	0.11	-9999	-0.43	20	20
mol:DAG	-0.03	0.18	-9999	-0.53	67	67
MAP2K2	-0.13	0.32	-9999	-0.57	324	324
MAP2K1	-0.13	0.32	-9999	-0.57	322	322
EDNRA	0.026	0.069	-9999	-0.42	5	5
positive regulation of muscle contraction	-0.013	0.17	-9999	-0.52	84	84
Gq family/GDP	-0.075	0.16	-9999	-0.63	49	49
HRAS/GTP	-0.053	0.21	-9999	-0.51	113	113
PRKCH	-0.024	0.17	-9999	-0.58	50	50
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.036	0.2	-9999	-0.63	66	66
PRKCB	-0.035	0.2	-9999	-0.62	61	61
PRKCE	-0.024	0.17	-9999	-0.58	50	50
PRKCD	-0.025	0.17	-9999	-0.57	50	50
PRKCG	-0.033	0.18	-9999	-0.53	65	65
regulation of vascular smooth muscle contraction	-0.3	0.57	-9999	-1.1	314	314
PRKCQ	-0.047	0.22	-9999	-0.63	86	86
PLA2G4A	-0.12	0.33	-9999	-0.69	175	175
GNA14	-0.005	0.091	-9999	-0.46	31	31
GNA15	0.006	0.036	-9999	-0.35	8	8
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.036	-9999	-0.8	2	2
Rac1/GTP	0.035	0.21	-9999	-0.56	84	84
MMP1	-0.12	0.12	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.004	0.039	-10000	0	-10000	0	0
EFNB1	0.017	0.053	-10000	0	-0.62	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.18	0.21	-10000	0	-0.42	423	423
Ephrin B2/EPHB1-2	-0.2	0.24	-10000	0	-0.48	422	422
neuron projection morphogenesis	-0.17	0.2	-10000	0	-0.4	423	423
Ephrin B1/EPHB1-2/Tiam1	-0.19	0.22	-10000	0	-0.45	423	423
DNM1	-0.006	0.067	-10000	0	-0.8	7	7
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.006	0.14	-10000	0	-0.75	33	33
YES1	-0.027	0.17	-10000	0	-0.99	32	32
Ephrin B1/EPHB1-2/NCK2	-0.19	0.22	-10000	0	-0.45	423	423
PI3K	-0.029	0.14	-10000	0	-0.71	41	41
mol:GDP	-0.19	0.22	-10000	0	-0.45	423	423
ITGA2B	-0.018	0.077	-10000	0	-0.31	57	57
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.028	0.17	-10000	0	-0.98	32	32
MAP3K7	-0.024	0.14	-10000	0	-0.8	32	32
FGR	-0.029	0.17	-10000	0	-0.99	32	32
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.047	0.17	-10000	0	-0.64	68	68
LYN	-0.027	0.17	-10000	0	-0.98	32	32
Ephrin B1/EPHB1-2/Src Family Kinases	-0.029	0.16	-10000	0	-0.93	32	32
Ephrin B1/EPHB1-2	-0.031	0.15	-10000	0	-0.87	32	32
SRC	-0.029	0.17	-10000	0	-0.99	32	32
ITGB3	-0.029	0.15	-10000	0	-0.75	39	39
EPHB1	-0.33	0.4	-10000	0	-0.8	423	423
EPHB4	0	0.009	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.63	38	38
BLK	-0.029	0.17	-10000	0	-0.99	32	32
HCK	-0.029	0.17	-10000	0	-0.99	32	32
regulation of stress fiber formation	0.19	0.22	0.45	423	-10000	0	423
MAPK8	0	0.14	-10000	0	-0.73	36	36
Ephrin B1/EPHB1-2/RGS3	-0.19	0.22	-10000	0	-0.45	423	423
endothelial cell migration	-0.018	0.12	-10000	0	-0.7	32	32
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.019	0.16	-10000	0	-0.92	32	32
regulation of focal adhesion formation	0.19	0.22	0.45	423	-10000	0	423
chemotaxis	0.19	0.22	0.45	423	-10000	0	423
PIK3CA	0	0.009	-10000	0	-0.29	1	1
Rac1/GTP	-0.17	0.2	-10000	0	-0.41	423	423
angiogenesis	-0.031	0.15	-10000	0	-0.86	32	32
LCK	-0.031	0.17	-10000	0	-0.99	32	32

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.22	0.42	-9999	-0.97	118	118
PLK1	-0.082	0.1	-9999	-10000	0	0
BIRC5	-0.093	0.098	-9999	-10000	0	0
HSPA1B	-0.22	0.42	-9999	-0.96	125	125
MAP2K1	0.009	0.029	-9999	-10000	0	0
BRCA2	-0.23	0.43	-9999	-0.97	128	128
FOXM1	-0.27	0.5	-9999	-1	204	204
XRCC1	-0.22	0.42	-9999	-0.95	130	130
FOXM1B/p19	-0.27	0.41	-9999	-0.91	209	209
Cyclin D1/CDK4	-0.21	0.4	-9999	-0.92	111	111
CDC2	-0.24	0.44	-9999	-0.9	204	204
TGFA	-0.21	0.41	-9999	-0.93	131	131
SKP2	-0.22	0.42	-9999	-0.96	124	124
CCNE1	-0.053	0.12	-9999	-0.3	202	202
CKS1B	-0.22	0.43	-9999	-0.95	130	130
RB1	-0.12	0.12	-9999	-0.87	1	1
FOXM1C/SP1	-0.28	0.44	-9999	-0.96	202	202
AURKB	-0.074	0.1	-9999	-10000	0	0
CENPF	-0.25	0.44	-9999	-0.93	185	185
CDK4	0.008	0.018	-9999	-0.3	1	1
MYC	-0.2	0.4	-9999	-0.88	142	142
CHEK2	0.008	0.032	-9999	-0.31	2	2
ONECUT1	-0.22	0.42	-9999	-0.94	135	135
CDKN2A	-0.036	0.11	-9999	-0.28	170	170
LAMA4	-0.22	0.43	-9999	-0.98	124	124
FOXM1B/HNF6	-0.26	0.47	-9999	-1.1	134	134
FOS	-0.43	0.67	-9999	-1.3	326	326
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.22	0.43	-9999	-0.96	127	127
response to radiation	-0.007	0.03	-9999	-10000	0	0
CENPB	-0.22	0.42	-9999	-0.95	131	131
CENPA	-0.25	0.45	-9999	-0.95	174	174
NEK2	-0.27	0.44	-9999	-0.94	181	181
HIST1H2BA	-0.23	0.42	-9999	-0.92	151	151
CCNA2	-0.11	0.15	-9999	-0.3	406	406
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.26	0.47	-9999	-1	164	164
CCNB2	-0.26	0.45	-9999	-0.94	178	178
CCNB1	-0.24	0.45	-9999	-0.96	175	175
ETV5	-0.22	0.43	-9999	-0.98	118	118
ESR1	-0.32	0.57	-9999	-1.3	211	211
CCND1	-0.21	0.41	-9999	-0.94	115	115
GSK3A	0.014	0.021	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.079	0.14	-9999	-0.32	171	171
CDK2	0.006	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.009	0.035	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.31	0.36	-9999	-0.9	207	207
GAS1	-0.26	0.48	-9999	-1.1	159	159
MMP2	-0.23	0.44	-9999	-0.98	132	132
RB1/FOXM1C	-0.22	0.43	-9999	-0.96	129	129
CREBBP	0	0	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.057	0.16	-10000	0	-0.54	103	103
cell-cell adhesion	0.18	0.22	0.68	72	-10000	0	72
Ephrin B/EPHB2/RasGAP	-0.04	0.12	-10000	0	-0.45	86	86
ITSN1	-0.001	0.025	-10000	0	-0.8	1	1
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.017	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.22	0.26	-10000	0	-0.54	422	422
HRAS/GDP	-0.18	0.23	-10000	0	-0.66	92	92
Ephrin B/EPHB1/GRB7	-0.23	0.28	-10000	0	-0.52	442	442
Endophilin/SYNJ1	-0.037	0.12	-10000	0	-0.42	86	86
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
Ephrin B/EPHB1/Src	-0.22	0.28	-10000	0	-0.52	441	441
endothelial cell migration	-0.005	0.045	-10000	0	-0.45	10	10
GRB2	0	0.009	-10000	0	-10000	0	0
GRB7	-0.02	0.076	-10000	0	-0.8	1	1
PAK1	-0.047	0.14	-10000	0	-0.46	97	97
HRAS	-0.002	0.025	-10000	0	-10000	0	0
RRAS	-0.038	0.12	-10000	0	-0.43	86	86
DNM1	-0.006	0.067	-10000	0	-0.8	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.21	0.26	-10000	0	-0.49	441	441
lamellipodium assembly	-0.18	0.22	-10000	0	-0.68	72	72
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.16	0.19	-10000	0	-0.36	422	422
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
EPHB2	-0.005	0.039	-10000	0	-10000	0	0
EPHB3	-0.004	0.032	-10000	0	-10000	0	0
EPHB1	-0.33	0.4	-10000	0	-0.8	423	423
EPHB4	0	0.009	-10000	0	-10000	0	0
mol:GDP	-0.16	0.21	-10000	0	-0.65	87	87
Ephrin B/EPHB2	-0.04	0.13	-10000	0	-0.46	86	86
Ephrin B/EPHB3	-0.04	0.13	-10000	0	-0.46	86	86
JNK cascade	-0.18	0.22	-10000	0	-0.44	422	422
Ephrin B/EPHB1	-0.23	0.28	-10000	0	-0.52	441	441
RAP1/GDP	-0.14	0.18	-10000	0	-0.61	67	67
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.068	0.22	-10000	0	-0.8	86	86
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.24	-10000	0	-0.49	422	422
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.19	0.23	-10000	0	-0.68	90	90
Rap1/GTP	-0.18	0.22	-10000	0	-0.71	71	71
axon guidance	-0.057	0.16	-10000	0	-0.53	103	103
MAPK3	-0.1	0.19	-10000	0	-0.53	67	67
MAPK1	-0.1	0.19	-10000	0	-0.53	67	67
Rac1/GDP	-0.14	0.19	-10000	0	-0.59	85	85
actin cytoskeleton reorganization	-0.14	0.17	-10000	0	-0.53	71	71
CDC42/GDP	-0.14	0.19	-10000	0	-0.59	85	85
PI3K	-0.005	0.045	-10000	0	-0.46	10	10
EFNA5	-0.081	0.24	-10000	0	-0.8	103	103
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.029	0.094	-10000	0	-0.33	86	86
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.17	0.21	-10000	0	-0.67	74	74
PTK2	0.044	0.051	-10000	0	-10000	0	0
MAP4K4	-0.19	0.22	-10000	0	-0.45	422	422
SRC	0	0.009	-10000	0	-0.29	1	1
KALRN	-0.016	0.11	-10000	0	-0.8	20	20
Intersectin/N-WASP	-0.001	0.019	-10000	0	-0.61	1	1
neuron projection morphogenesis	-0.14	0.18	-10000	0	-0.55	76	76
MAP2K1	-0.14	0.18	-10000	0	-0.56	68	68
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.2	0.24	-10000	0	-0.48	422	422
cell migration	-0.13	0.22	-10000	0	-0.57	87	87
NRAS	-0.001	0.013	-10000	0	-10000	0	0
SYNJ1	-0.038	0.12	-10000	0	-0.43	86	86
PXN	0	0	-10000	0	-10000	0	0
TF	-0.25	0.27	-10000	0	-0.46	586	586
HRAS/GTP	-0.19	0.24	-10000	0	-0.75	73	73
Ephrin B1/EPHB1-2	-0.2	0.24	-10000	0	-0.49	422	422
cell adhesion mediated by integrin	0.006	0.13	0.42	86	-10000	0	86
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.21	0.26	-10000	0	-0.48	441	441
RAC1-CDC42/GTP	-0.18	0.22	-10000	0	-0.69	72	72
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.14	0.18	-10000	0	-0.61	67	67
ruffle organization	-0.18	0.22	-10000	0	-0.7	72	72
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.003	0.14	-10000	0	-0.42	88	88
Ephrin B/EPHB2/KALRN	-0.048	0.15	-10000	0	-0.49	97	97
ROCK1	-0.002	0.021	-10000	0	-0.49	1	1
RAS family/GDP	-0.12	0.16	-10000	0	-0.53	68	68
Rac1/GTP	-0.19	0.24	-10000	0	-0.75	72	72
Ephrin B/EPHB1/Src/Paxillin	-0.16	0.2	-10000	0	-0.38	441	441

×

ErbB2/ErbB3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.38	22	22
NFATC4	-0.089	0.16	-9999	-0.36	27	27
ERBB2IP	0.007	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-10000	0	0
mammary gland morphogenesis	-0.15	0.19	-9999	-0.39	377	377
JUN	-0.018	0.081	-9999	-0.37	6	6
HRAS	-0.002	0.025	-9999	-10000	0	0
DOCK7	-0.13	0.19	-9999	-0.39	166	166
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.22	-9999	-0.47	377	377
AKT1	0.007	0.006	-9999	-10000	0	0
BAD	0.018	0.007	-9999	-10000	0	0
MAPK10	-0.11	0.14	-9999	-0.36	160	160
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.2	-9999	-0.42	377	377
RAF1	-0.081	0.16	-9999	-0.43	10	10
ErbB2/ErbB3/neuregulin 2	-0.26	0.25	-9999	-0.51	507	507
STAT3	0.001	0.004	-9999	-10000	0	0
cell migration	-0.063	0.13	-9999	-0.31	86	86
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.23	-9999	-0.51	160	160
FOS	-0.16	0.26	-9999	-0.54	309	309
NRAS	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	-0.15	0.19	-9999	-0.39	377	377
MAPK3	-0.11	0.19	-9999	-0.48	61	61
MAPK1	-0.11	0.19	-9999	-0.48	60	60
JAK2	-0.13	0.19	-9999	-0.37	378	378
NF2	-0.006	0.01	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.17	-9999	-0.36	377	377
NRG1	-0.29	0.39	-9999	-0.8	375	375
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.33	380	380
MAPK9	-0.07	0.088	-9999	-0.28	1	1
ERBB2	-0.016	0.054	-9999	-10000	0	0
ERBB3	0.001	0.044	-9999	-0.8	3	3
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.015	0.017	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.004	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.007	0.005	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.099	0.13	-9999	-0.32	23	23
ErbB2/ErbB2/HSP90 (dimer)	-0.012	0.042	-9999	-10000	0	0
CHRNA1	-0.091	0.16	-9999	-0.41	54	54
myelination	-0.083	0.16	-9999	-0.36	27	27
PPP3CB	-0.13	0.16	-9999	-0.34	377	377
KRAS	-0.001	0.013	-9999	-0.28	2	2
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.37	19	19
NRG2	-0.4	0.4	-9999	-0.8	504	504
mol:GDP	-0.12	0.18	-9999	-0.36	377	377
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.073	0.15	-9999	-0.44	9	9
SRC	0	0.009	-9999	-0.29	1	1
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.37	377	377
MAP2K1	-0.13	0.21	-9999	-0.49	157	157
heart morphogenesis	-0.15	0.19	-9999	-0.39	377	377
RAS family/GDP	-0.11	0.14	-9999	-0.48	6	6
GRB2	0	0.009	-9999	-10000	0	0
PRKACA	-0.01	0.014	-9999	-10000	0	0
CHRNE	0.007	0.023	-9999	-0.18	6	6
HSP90AA1	0	0.009	-9999	-10000	0	0
activation of caspase activity	-0.007	0.006	-9999	-10000	0	0
nervous system development	-0.15	0.19	-9999	-0.39	377	377
CDC42	0	0	-9999	-10000	0	0

×

IGF1 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
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.1	0.24	-10000	0	-0.5	248	248
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.002	0.025	-10000	0	-10000	0	0
IRS1/Crk	-0.12	0.23	-10000	0	-0.5	248	248
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.24	-10000	0	-0.54	234	234
AKT1	-0.068	0.22	-10000	0	-0.74	48	48
BAD	-0.055	0.2	-10000	0	-0.68	47	47
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.24	-10000	0	-0.5	248	248
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.23	-10000	0	-0.5	248	248
RAF1	-0.048	0.19	-10000	0	-0.64	45	45
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.11	0.22	-10000	0	-0.47	248	248
YWHAZ	-0.001	0.015	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.25	-10000	0	-0.54	248	248
PIK3CA	0	0.009	-10000	0	-0.29	1	1
RPS6KB1	-0.068	0.22	-10000	0	-0.74	48	48
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.04	0.16	-10000	0	-0.52	45	45
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.2	-10000	0	-0.73	44	44
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.099	0.19	-10000	0	-0.43	234	234
IGF-1R heterotetramer	-0.034	0.14	-10000	0	-0.67	35	35
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.23	-10000	0	-0.5	248	248
Crk/p130 Cas/Paxillin	-0.11	0.21	-10000	0	-0.45	234	234
IGF1R	-0.034	0.14	-10000	0	-0.67	35	35
IGF1	-0.18	0.35	-10000	0	-0.83	225	225
IRS2/Crk	-0.13	0.25	-10000	0	-0.51	261	261
PI3K	-0.12	0.23	-10000	0	-0.48	249	249
apoptosis	0.081	0.15	0.56	46	-10000	0	46
HRAS/GDP	-0.002	0.017	-10000	0	-10000	0	0
PRKCD	-0.094	0.25	-10000	0	-0.54	234	234
RAF1/14-3-3 E	-0.076	0.14	-10000	0	-0.53	45	45
BAD/14-3-3	-0.086	0.16	-10000	0	-0.61	46	46
PRKCZ	-0.069	0.22	-10000	0	-0.73	49	49
Crk/p130 Cas/Paxillin/FAK1	-0.085	0.16	-10000	0	-0.63	45	45
PTPN1	-0.003	0.03	-10000	0	-0.29	11	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.13	0.25	-10000	0	-0.57	234	234
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.21	-10000	0	-0.47	234	234
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.23	-10000	0	-0.49	248	248
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.24	-10000	0	-0.5	248	248
IRS1	-0.13	0.25	-10000	0	-0.54	248	248
IRS2	-0.12	0.28	-10000	0	-0.54	261	261
IGF-1R heterotetramer/IGF1	-0.16	0.29	-10000	0	-0.67	234	234
GRB2	0	0.009	-10000	0	-10000	0	0
PDPK1	-0.11	0.21	-10000	0	-0.46	235	235
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.58	245	245
SHC1	0	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.01	0.039	-9999	-0.54	3	3
NFATC2	-0.04	0.16	-9999	-0.56	92	92
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.22	0.37	-9999	-0.72	289	289
PTGS2	-0.33	0.47	-9999	-0.86	401	401
JUNB	-0.001	0.013	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.009	-9999	-10000	0	0
CALM1	0	0.003	-9999	-10000	0	0
JUN	-0.007	0.076	-9999	-0.81	9	9
mol:Ca2+	-0.007	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
FOSL1	-0.008	0.055	-9999	-0.33	25	25
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.077	0.15	-9999	-0.52	79	79
FOS	-0.25	0.38	-9999	-0.82	307	307
IFNG	-0.22	0.35	-9999	-0.69	295	295
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.83	303	303
FASLG	-0.21	0.35	-9999	-0.69	285	285
NFAT1-c-4/ICER1	-0.058	0.14	-9999	-0.48	95	95
IL2RA	-0.21	0.35	-9999	-0.7	286	286
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.21	0.34	-9999	-0.68	284	284
JunB/Fra1/NFAT1-c-4	-0.056	0.14	-9999	-0.49	70	70
IL4	-0.21	0.34	-9999	-0.68	283	283
IL2	-0.01	0.025	-9999	-10000	0	0
IL3	-0.024	0.026	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-0.29	1	1
BATF3	-0.002	0.029	-9999	-0.42	4	4
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-0.29	1	1

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.026	0.062	-10000	0	-0.5	2	2
epithelial cell differentiation	-0.021	0.063	-10000	0	-0.49	6	6
ITCH	0.009	0.021	-10000	0	-10000	0	0
WWP1	0.008	0.068	-10000	0	-10000	0	0
FYN	-0.002	0.036	-10000	0	-0.8	2	2
EGFR	-0.3	0.39	-10000	0	-0.8	384	384
PRL	-0.004	0.032	-10000	0	-0.29	13	13
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.47	63	63
PTPRZ1	-0.42	0.4	-10000	0	-0.8	535	535
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.2	-10000	0	-0.52	68	68
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.2	0.24	-10000	0	-0.5	375	375
ADAM17	0.009	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0.001	0.086	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.058	0.14	-10000	0	-0.54	61	61
NCOR1	-0.001	0.025	-10000	0	-0.8	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.22	-10000	0	-0.47	375	375
GRIN2B	-0.18	0.25	-10000	0	-0.46	423	423
ErbB4/ErbB2/betacellulin	-0.049	0.11	-10000	0	-0.47	57	57
STAT1	-0.005	0.038	-10000	0	-10000	0	0
HBEGF	-0.002	0.036	-10000	0	-0.8	2	2
PRLR	-0.007	0.066	-10000	0	-0.52	13	13
E4ICDs/ETO2	-0.035	0.093	-10000	0	-0.56	19	19
axon guidance	0.044	0.12	-10000	0	-0.42	2	2
NEDD4	0.009	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.007	0.054	-10000	0	-0.62	6	6
CBFA2T3	-0.016	0.11	-10000	0	-0.7	24	24
ErbB4/ErbB2/HBEGF	-0.024	0.05	-10000	0	-0.44	2	2
MAPK3	-0.15	0.19	-10000	0	-0.49	68	68
STAT1 (dimer)	-0.028	0.063	-10000	0	-10000	0	0
MAPK1	-0.15	0.19	-10000	0	-0.49	64	64
JAK2	-0.001	0.025	-10000	0	-0.8	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.22	-10000	0	-0.48	375	375
NRG1	-0.21	0.31	-10000	0	-0.62	375	375
NRG3	-0.054	0.19	-10000	0	-0.8	61	61
NRG2	-0.4	0.4	-10000	0	-0.8	504	504
NRG4	-0.005	0.038	-10000	0	-10000	0	0
heart development	0.044	0.12	-10000	0	-0.42	2	2
neural crest cell migration	-0.19	0.22	-10000	0	-0.47	375	375
ERBB2	0.011	0.057	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.026	0.059	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.2	0.22	-10000	0	-0.47	379	379
apoptosis	0.059	0.14	0.53	61	-10000	0	61
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.27	0.24	-10000	0	-0.51	504	504
ErbB4/ErbB2/epiregulin	-0.086	0.15	-10000	0	-0.46	123	123
ErbB4/ErbB4/betacellulin/betacellulin	-0.053	0.13	-10000	0	-0.51	57	57
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.022	0.065	-10000	0	-0.52	9	9
MDM2	0.009	0.074	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.23	-10000	0	-0.48	375	375
STAT5A	0.044	0.12	-10000	0	-0.48	6	6
ErbB4/EGFR/neuregulin 1 beta	-0.35	0.36	-10000	0	-0.67	521	521
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.055	-10000	0	-0.47	1	1
STAT5A (dimer)	-0.021	0.067	-10000	0	-0.54	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.026	0.11	-10000	0	-0.44	4	4
LRIG1	-0.002	0.036	-10000	0	-0.8	2	2
EREG	-0.12	0.26	-10000	0	-0.6	199	199
BTC	-0.045	0.18	-10000	0	-0.8	57	57
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.044	0.12	-10000	0	-0.42	2	2
ERBB4	-0.031	0.072	-10000	0	-10000	0	0
STAT5B	-0.002	0.043	-10000	0	-0.8	3	3
YAP1	-0.01	0.044	-10000	0	-0.64	4	4
GRB2	0	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.026	0.051	-10000	0	-10000	0	0
glial cell differentiation	0.023	0.055	0.46	1	-10000	0	1
WWOX	-0.001	0.013	-10000	0	-10000	0	0
cell proliferation	-0.12	0.24	-10000	0	-0.58	71	71

×

Nongenotropic Androgen signaling

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
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.067	0.17	-10000	0	-0.49	138	138
regulation of S phase of mitotic cell cycle	-0.041	0.12	-10000	0	-0.35	130	130
GNAO1	-0.031	0.14	-10000	0	-0.48	66	66
HRAS	-0.002	0.025	-10000	0	-0.29	1	1
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.001	-10000	0	-10000	0	0
MAP2K1	-0.042	0.16	-10000	0	-0.43	127	127
T-DHT/AR	-0.078	0.21	-10000	0	-0.63	127	127
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	307	307
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	49	49
mol:GDP	-0.079	0.21	-10000	0	-0.63	127	127
cell proliferation	-0.1	0.24	-10000	0	-0.56	98	98
PIK3CA	0	0.009	-10000	0	-0.29	1	1
FOS	-0.23	0.42	-10000	0	-0.87	307	307
mol:Ca2+	-0.016	0.027	-10000	0	-0.077	131	131
MAPK3	-0.074	0.2	-10000	0	-0.61	60	60
MAPK1	-0.046	0.12	-10000	0	-0.31	57	57
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.001	0.002	-10000	0	-0.005	307	307
cAMP biosynthetic process	0.012	0.024	-10000	0	-10000	0	0
GNG2	-0.009	0.087	-10000	0	-0.8	12	12
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	307	307
HRAS/GTP	-0.065	0.15	-10000	0	-0.46	127	127
actin cytoskeleton reorganization	-0.004	0.043	-10000	0	-0.43	10	10
SRC	0	0.009	-10000	0	-0.28	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	307	307
PI3K	-0.005	0.053	-10000	0	-0.54	10	10
apoptosis	0.11	0.23	0.43	307	-10000	0	307
T-DHT/AR/PELP1	-0.068	0.18	-10000	0	-0.54	127	127
HRAS/GDP	-0.076	0.2	-10000	0	-0.6	128	128
CREB1	-0.12	0.24	-10000	0	-0.46	307	307
RAC1-CDC42/GTP	-0.004	0.043	-10000	0	-0.44	10	10
AR	-0.1	0.27	-10000	0	-0.8	128	128
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.043	0.16	-10000	0	-0.45	127	127
RAC1-CDC42/GDP	-0.071	0.19	-10000	0	-0.56	127	127
T-DHT/AR/PELP1/Src	-0.062	0.16	-10000	0	-0.5	127	127
MAP2K2	-0.042	0.16	-10000	0	-0.43	127	127
T-DHT/AR/PELP1/Src/PI3K	-0.041	0.12	-10000	0	-0.35	130	130
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.037	0.11	-10000	0	-0.49	36	36
mol:T-DHT	-0.001	0.001	0.001	57	-0.003	248	305
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.005	0.059	-10000	0	-0.62	9	9
Gi family/GTP	-0.048	0.1	-10000	0	-0.3	83	83
CDC42	0	0	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	-0.1	0.23	-10000	0	-0.61	170	170
CRKL	-0.039	0.16	-10000	0	-0.35	170	170
mol:PIP3	-0.018	0.036	0.79	2	-10000	0	2
AKT1	0.003	0.022	0.49	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.029	0.15	-10000	0	-0.55	20	20
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
HGF/MET/SHIP2	-0.12	0.24	-10000	0	-0.57	217	217
MAP3K5	-0.02	0.15	-10000	0	-0.54	24	24
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.11	0.22	-10000	0	-0.52	217	217
AP1	-0.19	0.27	-10000	0	-0.59	308	308
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.24	0.37	-10000	0	-0.78	308	308
STAT3 (dimer)	-0.038	0.16	-10000	0	-0.34	217	217
GAB1/CRKL/SHP2/PI3K	-0.064	0.13	-10000	0	-0.54	26	26
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.065	0.13	-10000	0	-0.55	20	20
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.8	2	2
ELK1	-0.043	0.1	-10000	0	-0.27	170	170
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.046	0.093	-10000	0	-0.42	20	20
PAK1	0.008	0.029	0.45	2	-10000	0	2
HGF/MET/RANBP10	-0.12	0.24	-10000	0	-0.57	217	217
HRAS	-0.15	0.3	-10000	0	-0.69	217	217
DOCK1	-0.029	0.15	-10000	0	-0.55	20	20
GAB1	-0.049	0.16	-10000	0	-0.35	217	217
CRK	-0.039	0.16	-10000	0	-0.35	170	170
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.3	-10000	0	-0.71	217	217
JUN	-0.007	0.075	-10000	0	-0.8	9	9
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.076	0.15	-10000	0	-0.36	217	217
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
cell morphogenesis	-0.017	0.17	-10000	0	-0.6	26	26
GRB2/SHC	-0.066	0.13	-10000	0	-0.33	170	170
FOS	-0.24	0.37	-10000	0	-0.8	307	307
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.043	0.1	-10000	0	-0.27	170	170
HGF/MET/MUC20	-0.12	0.25	-10000	0	-0.58	217	217
cell migration	-0.065	0.13	-10000	0	-0.33	170	170
GRB2	0	0.009	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.1	0.23	-10000	0	-0.61	170	170
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.076	0.15	-10000	0	-0.36	217	217
MET/MUC20	-0.1	0.23	-10000	0	-0.62	171	171
RAP1B	-0.019	0.14	-10000	0	-0.5	20	20
RAP1A	-0.019	0.14	-10000	0	-0.5	20	20
HGF/MET/RANBP9	-0.12	0.24	-10000	0	-0.57	217	217
RAF1	-0.1	0.29	-10000	0	-0.71	173	173
STAT3	-0.072	0.14	-10000	0	-0.34	217	217
cell proliferation	-0.059	0.23	-10000	0	-0.48	217	217
RPS6KB1	-0.026	0.052	-10000	0	-0.18	20	20
MAPK3	-0.044	0.092	-10000	0	-0.25	170	170
MAPK1	-0.044	0.092	-10000	0	-0.25	170	170
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.14	-10000	0	-0.47	30	30
SRC	-0.07	0.14	-10000	0	-0.62	20	20
PI3K	-0.07	0.14	-10000	0	-0.35	178	178
MET/Glomulin	-0.093	0.21	-10000	0	-0.56	170	170
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.084	0.27	-10000	0	-0.65	170	170
MET	-0.13	0.3	-10000	0	-0.8	171	171
MAP4K1	-0.028	0.15	-10000	0	-0.33	171	171
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.084	0.27	-10000	0	-0.65	170	170
BAD	0.011	0.021	0.45	2	-10000	0	2
MAP2K4	-0.01	0.14	-10000	0	-0.48	25	25
SHP2/GRB2/SOS1/GAB1	-0.095	0.19	-10000	0	-0.51	170	170
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.07	0.14	-10000	0	-0.36	170	170
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.053	0.2	-10000	0	-0.8	67	67
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.066	0.13	-10000	0	-0.33	170	170
PDPK1	-0.006	0.026	0.57	2	-10000	0	2
HGF/MET/SHIP	-0.12	0.24	-10000	0	-0.57	217	217

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.2	-9999	-0.6	124	124
SMAD6-7/SMURF1	-0.001	0.017	-9999	-0.53	1	1
NOG	-0.023	0.12	-9999	-0.57	41	41
SMAD9	-0.11	0.26	-9999	-0.78	114	114
SMAD4	-0.001	0.025	-9999	-0.8	1	1
SMAD5	-0.075	0.18	-9999	-0.48	131	131
BMP7/USAG1	-0.35	0.35	-9999	-0.67	528	528
SMAD5/SKI	-0.087	0.16	-9999	-0.46	117	117
SMAD1	0.026	0.03	-9999	-10000	0	0
BMP2	-0.14	0.31	-9999	-0.8	181	181
SMAD1/SMAD1/SMAD4	-0.002	0.015	-9999	-10000	0	0
BMPR1A	-0.002	0.036	-9999	-0.8	2	2
BMPR1B	-0.14	0.18	-9999	-0.8	25	25
BMPR1A-1B/BAMBI	-0.092	0.14	-9999	-0.6	57	57
AHSG	-0.003	0.031	-9999	-0.29	12	12
CER1	-0.001	0.015	-9999	-0.29	3	3
BMP2-4/CER1	-0.13	0.25	-9999	-0.58	226	226
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.2	-9999	-0.52	143	143
BMP2-4 (homodimer)	-0.15	0.28	-9999	-0.66	226	226
RGMB	-0.001	0.025	-9999	-0.8	1	1
BMP6/BMPR2/BMPR1A-1B	-0.097	0.16	-9999	-0.54	102	102
RGMA	-0.11	0.28	-9999	-0.8	138	138
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.62	102	102
BMP2-4/USAG1	-0.38	0.37	-9999	-0.66	587	587
SMAD6/SMURF1/SMAD5	-0.087	0.16	-9999	-0.49	98	98
SOSTDC1	-0.4	0.4	-9999	-0.8	507	507
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.58	100	100
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.061	0.21	-9999	-0.79	79	79
HFE2	-0.002	0.025	-9999	-0.29	8	8
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-0.29	1	1
BMP2-4/CHRD	-0.14	0.27	-9999	-0.62	230	230
SMAD5/SMAD5/SMAD4	-0.088	0.16	-9999	-0.51	88	88
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.087	0.17	-9999	-0.53	100	100
BMP7 (homodimer)	-0.074	0.22	-9999	-0.64	118	118
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.049	0.16	-9999	-0.62	77	77
SMAD1/SKI	0.004	0.019	-9999	-10000	0	0
SMAD6	-0.001	0.025	-9999	-0.8	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.13	0.25	-9999	-0.58	226	226
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.038	0.12	-9999	-0.35	110	110
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.01	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.09	0.12	-9999	-0.62	27	27
CHRDL1	-0.55	0.37	-9999	-0.8	697	697
ENDOFIN/SMAD1	0.004	0.019	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.014	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.035	0.14	-9999	-0.51	70	70
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.48	0.37	-9999	-0.68	714	714
BMP2-4/GREM1	-0.15	0.26	-9999	-0.59	231	231
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.1	0.24	-9999	-0.73	113	113
SMAD1/SMAD6	0.004	0.019	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.074	0.22	-9999	-0.64	118	118
BMP6	-0.061	0.21	-9999	-0.79	79	79
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.1	0.19	-9999	-0.6	99	99
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	0.004	0.019	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.001	0.02	-9999	-0.29	5	5
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.58	160	160
CHRD	-0.033	0.13	-9999	-0.8	21	21
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.24	-9999	-0.54	189	189
BMP4	-0.052	0.2	-9999	-0.8	67	67
FST	-0.034	0.16	-9999	-0.76	46	46
BMP2-4/NOG	-0.14	0.26	-9999	-0.59	239	239
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.093	0.16	-9999	-0.55	100	100

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.035	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.081	0.16	-9999	-0.47	90	90
JUN	-0.05	0.14	-9999	-0.53	27	27
HRAS	-0.002	0.025	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.2	-9999	-0.53	190	190
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.2	-9999	-0.53	190	190
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.19	-9999	-0.5	181	181
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.48	187	187
GRB7	-0.02	0.076	-9999	-0.8	1	1
RET51/GFRalpha1/GDNF	-0.15	0.2	-9999	-0.53	190	190
MAPKKK cascade	-0.097	0.17	-9999	-0.54	48	48
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.23	-9999	-0.57	193	193
lamellipodium assembly	-0.081	0.15	-9999	-0.37	188	188
RET51/GFRalpha1/GDNF/SHC	-0.15	0.2	-9999	-0.53	190	190
PIK3CA	0	0.009	-9999	-0.29	1	1
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.5	181	181
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.5	181	181
MAPK3	-0.12	0.17	-9999	-0.45	187	187
DOK1	-0.001	0.018	-9999	-10000	0	0
DOK6	-0.013	0.096	-9999	-0.8	14	14
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.54	54	54
DOK5	-0.02	0.12	-9999	-0.71	28	28
GFRA1	-0.16	0.31	-9999	-0.8	181	181
MAPK8	-0.074	0.13	-9999	-0.44	53	53
HRAS/GTP	-0.12	0.19	-9999	-0.49	187	187
tube development	-0.094	0.18	-9999	-0.46	181	181
MAPK1	-0.12	0.17	-9999	-0.45	187	187
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.064	0.13	-9999	-0.34	181	181
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.2	-9999	-0.52	193	193
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.2	-9999	-0.53	190	190
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.56	205	205
PRKCA	-0.021	0.13	-9999	-0.8	26	26
HRAS/GDP	-0.002	0.017	-9999	-10000	0	0
CREB1	-0.071	0.15	-9999	-0.38	181	181
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.064	0.13	-9999	-0.34	181	181
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.55	192	192
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.11	0.16	-9999	-0.31	380	380
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.049	0.14	-9999	-0.52	27	27
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.5	181	181
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.064	0.13	-9999	-0.34	181	181
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.14	-9999	-0.36	187	187
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.08	0.14	-9999	-0.36	187	187
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.082	0.15	-9999	-0.37	187	187
PI3K	-0.13	0.24	-9999	-0.6	188	188
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.094	0.18	-9999	-0.46	181	181
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.076	0.13	-9999	-0.41	46	46
RET51/GFRalpha1/GDNF/FRS2	-0.15	0.2	-9999	-0.53	190	190
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.034	0.16	-9999	-0.8	43	43
IRS2	-0.032	0.16	-9999	-0.8	41	41
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.082	0.15	-9999	-0.37	187	187
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.22	-9999	-0.55	214	214
GRB2	0	0.009	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.015	0.065	-9999	-0.29	55	55
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.6	201	201
Rac1/GTP	-0.098	0.18	-9999	-0.45	188	188
RET9/GFRalpha1/GDNF	-0.11	0.21	-9999	-0.54	185	185
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.62	185	185

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.22	0.27	-10000	0	-0.54	415	415
fibroblast growth factor receptor signaling pathway	-0.22	0.26	-10000	0	-0.53	415	415
LAMA1	-0.095	0.26	-10000	0	-0.79	123	123
PRNP	-0.013	0.1	-10000	0	-0.8	16	16
GPC1/SLIT2	-0.066	0.19	-10000	0	-0.61	109	109
SMAD2	0.01	0.1	-10000	0	-0.48	44	44
GPC1/PrPc/Cu2+	-0.01	0.069	-10000	0	-0.54	17	17
GPC1/Laminin alpha1	-0.074	0.2	-10000	0	-0.61	121	121
TDGF1	-0.008	0.08	-10000	0	-0.76	11	11
CRIPTO/GPC1	-0.008	0.065	-10000	0	-0.61	11	11
APP/GPC1	-0.001	0.023	-10000	0	-0.61	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.018	0.061	-10000	0	-0.53	12	12
FLT1	-0.001	0.025	-10000	0	-0.8	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.024	0.11	-10000	0	-0.53	44	44
SERPINC1	-0.015	0.064	-10000	0	-0.29	54	54
FYN	0.018	0.063	-10000	0	-0.53	13	13
FGR	0.019	0.059	-10000	0	-0.53	11	11
positive regulation of MAPKKK cascade	0.031	0.073	-10000	0	-0.54	12	12
SLIT2	-0.085	0.25	-10000	0	-0.8	108	108
GPC1/NRG	-0.23	0.3	-10000	0	-0.61	376	376
NRG1	-0.3	0.39	-10000	0	-0.8	375	375
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.029	-10000	0	-0.53	2	2
LYN	0.019	0.059	-10000	0	-0.53	11	11
mol:Spermine	0.01	0.024	-10000	0	-0.62	1	1
cell growth	-0.22	0.26	-10000	0	-0.53	415	415
BMP signaling pathway	0.002	0.032	0.37	6	-10000	0	6
SRC	0.019	0.059	-10000	0	-0.53	11	11
TGFBR1	0	0.009	-10000	0	-0.29	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.27	0.37	-10000	0	-0.76	359	359
GPC1	-0.002	0.032	-10000	0	-0.37	6	6
TGFBR1 (dimer)	0	0.009	-10000	0	-0.28	1	1
VEGFA	-0.003	0.03	-10000	0	-10000	0	0
BLK	-0.007	0.087	-10000	0	-0.56	13	13
HCK	0.017	0.061	-10000	0	-0.53	11	11
FGF2	-0.32	0.39	-10000	0	-0.8	409	409
FGFR1	-0.01	0.084	-10000	0	-0.69	14	14
VEGFR1 homodimer	-0.001	0.025	-10000	0	-0.8	1	1
TGFBR2	-0.034	0.16	-10000	0	-0.8	43	43
cell death	-0.001	0.023	-10000	0	-0.61	1	1
ATIII/GPC1	-0.011	0.046	-10000	0	-0.62	1	1
PLA2G2A/GPC1	-0.21	0.29	-10000	0	-0.62	333	333
LCK	0.006	0.09	-10000	0	-0.54	24	24
neuron differentiation	-0.23	0.29	-10000	0	-0.61	376	376
PrPc/Cu2+	-0.01	0.077	-10000	0	-0.62	16	16
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.034	0.16	-10000	0	-0.8	43	43

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.17	0.4	-9999	-1	87	87
IL23A	-0.17	0.4	-9999	-1	94	94
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.32	-9999	-0.89	129	129
positive regulation of T cell mediated cytotoxicity	-0.19	0.43	-9999	-0.86	222	222
ITGA3	-0.17	0.39	-9999	-0.98	92	92
IL17F	-0.11	0.28	-9999	-0.66	87	87
IL12B	-0.048	0.12	-9999	-0.3	103	103
STAT1 (dimer)	-0.22	0.38	-9999	-0.88	171	171
CD4	-0.16	0.38	-9999	-0.9	113	113
IL23	-0.18	0.39	-9999	-0.99	94	94
IL23R	-0.013	0.088	-9999	-10000	0	0
IL1B	-0.18	0.41	-9999	-1.1	98	98
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.17	0.38	-9999	-0.96	96	96
TYK2	0.011	0.017	-9999	-10000	0	0
STAT4	-0.033	0.16	-9999	-0.79	42	42
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.025	0.15	-9999	-0.75	40	40
IL12RB1	-0.001	0.069	-9999	-0.32	40	40
PIK3CA	0	0.009	-9999	-0.28	1	1
IL12Rbeta1/TYK2	-0.002	0.052	-9999	-0.62	2	2
IL23R/JAK2	-0.011	0.11	-9999	-0.64	1	1
positive regulation of chronic inflammatory response	-0.19	0.43	-9999	-0.86	222	222
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.018	0.035	-9999	-0.84	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
NFKB1	0.003	0.006	-9999	-10000	0	0
RELA	0.003	0.006	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.17	0.37	-9999	-0.93	96	96
ALOX12B	-0.17	0.38	-9999	-0.96	91	91
CXCL1	-0.36	0.64	-9999	-1.4	272	272
T cell proliferation	-0.19	0.43	-9999	-0.86	222	222
NFKBIA	0.003	0.006	-9999	-10000	0	0
IL17A	-0.07	0.24	-9999	-0.54	54	54
PI3K	-0.25	0.33	-9999	-0.85	168	168
IFNG	-0.005	0.026	-9999	-0.089	25	25
STAT3 (dimer)	-0.24	0.32	-9999	-0.88	128	128
IL18R1	-0.009	0.1	-9999	-0.8	17	17
IL23/IL23R/JAK2/TYK2/SOCS3	-0.084	0.24	-9999	-0.56	55	55
IL18/IL18R	-0.031	0.12	-9999	-0.55	51	51
macrophage activation	-0.013	0.017	-9999	-0.04	137	137
TNF	-0.18	0.41	-9999	-0.99	120	120
STAT3/STAT4	-0.26	0.35	-9999	-0.88	187	187
STAT4 (dimer)	-0.23	0.4	-9999	-0.9	202	202
IL18	-0.003	0.046	-9999	-0.29	26	26
IL19	-0.18	0.38	-9999	-0.9	123	123
STAT5A (dimer)	-0.22	0.38	-9999	-0.85	199	199
STAT1	-0.005	0.038	-9999	-10000	0	0
SOCS3	-0.005	0.061	-9999	-0.8	6	6
CXCL9	-0.18	0.39	-9999	-0.94	120	120
MPO	-0.21	0.47	-9999	-1.1	166	166
positive regulation of humoral immune response	-0.19	0.43	-9999	-0.86	222	222
IL23/IL23R/JAK2/TYK2	-0.2	0.45	-9999	-0.91	210	210
IL6	-0.46	0.7	-9999	-1.3	381	381
STAT5A	-0.006	0.071	-9999	-0.8	8	8
IL2	0.003	0.029	-9999	-0.3	9	9
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.18	0.41	-9999	-0.99	120	120
keratinocyte proliferation	-0.19	0.43	-9999	-0.86	222	222
NOS2	-0.17	0.39	-9999	-0.95	105	105

×

Noncanonical Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.072	0.23	-9999	-0.8	92	92
GNB1/GNG2	-0.14	0.23	-9999	-0.68	104	104
mol:DAG	-0.13	0.2	-9999	-0.6	104	104
PLCG1	-0.13	0.21	-9999	-0.63	104	104
YES1	-0.15	0.23	-9999	-0.66	109	109
FZD3	-0.009	0.083	-9999	-0.8	11	11
FZD6	-0.006	0.071	-9999	-0.8	8	8
G protein	-0.13	0.21	-9999	-0.63	106	106
MAP3K7	-0.068	0.19	-9999	-0.49	101	101
mol:Ca2+	-0.092	0.21	-9999	-0.58	104	104
mol:IP3	-0.13	0.2	-9999	-0.6	104	104
NLK	-0.005	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.082	0.2	-9999	-0.53	106	106
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.16	0.24	-9999	-0.44	361	361
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.15	0.23	-9999	-0.66	108	108
GO:0007205	-0.094	0.22	-9999	-0.59	104	104
WNT6	-0.17	0.32	-9999	-0.71	241	241
WNT4	-0.021	0.12	-9999	-0.8	20	20
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.62	134	134
GNG2	-0.009	0.087	-9999	-0.8	12	12
WNT5A	-0.015	0.1	-9999	-0.6	25	25
WNT11	-0.17	0.32	-9999	-0.8	212	212
CDC42	-0.11	0.23	-9999	-0.66	95	95

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.096	0.18	-10000	0	-0.47	180	180
ER alpha/Gai/GDP/Gbeta gamma	-0.09	0.19	-10000	0	-0.47	174	174
AKT1	-0.098	0.32	-10000	0	-0.84	154	154
PIK3CA	0	0.009	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.1	0.32	-10000	0	-0.86	151	151
mol:Ca2+	-0.028	0.15	-10000	0	-0.56	35	35
IGF1R	-0.021	0.12	-10000	0	-0.61	35	35
E2/ER alpha (dimer)/Striatin	-0.11	0.2	-10000	0	-0.55	166	166
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.09	0.3	0.8	154	-10000	0	154
RhoA/GTP	-0.07	0.14	-10000	0	-0.4	151	151
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.09	0.21	-10000	0	-0.54	160	160
regulation of stress fiber formation	0.023	0.14	0.37	30	-10000	0	30
E2/ERA-ERB (dimer)	-0.11	0.2	-10000	0	-0.55	172	172
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
G13/GTP	-0.09	0.17	-10000	0	-0.49	151	151
pseudopodium formation	-0.023	0.14	-10000	0	-0.37	30	30
E2/ER alpha (dimer)/PELP1	-0.098	0.19	-10000	0	-0.54	151	151
GRB2	0	0.009	-10000	0	-10000	0	0
GNG2	-0.009	0.087	-10000	0	-0.8	12	12
GNAO1	-0.031	0.14	-10000	0	-0.48	66	66
HRAS	-0.002	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.058	0.22	-10000	0	-0.55	161	161
E2/ER beta (dimer)	-0.013	0.09	-10000	0	-0.62	22	22
mol:GDP	-0.085	0.2	-10000	0	-0.54	172	172
mol:NADP	-0.058	0.22	-10000	0	-0.55	161	161
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.03	0.15	-10000	0	-0.59	34	34
IGF-1R heterotetramer	-0.021	0.12	-10000	0	-0.61	35	35
PLCB1	-0.064	0.14	-10000	0	-0.5	84	84
PLCB2	-0.034	0.091	-10000	0	-0.64	14	14
IGF1	-0.18	0.33	-10000	0	-0.8	225	225
mol:L-citrulline	-0.058	0.22	-10000	0	-0.55	161	161
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.038	0.15	-10000	0	-0.85	25	25
JNK cascade	-0.013	0.09	-10000	0	-0.62	22	22
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.017	0.12	-10000	0	-0.8	22	22
GNAQ	-0.002	0.036	-10000	0	-0.8	2	2
ESR1	-0.15	0.29	-10000	0	-0.57	277	277
Gq family/GDP/Gbeta gamma	-0.007	0.071	-10000	0	-0.72	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.023	0.13	-10000	0	-0.36	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.09	0.21	-10000	0	-0.54	160	160
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.62	151	151
STRN	-0.014	0.11	-10000	0	-0.8	18	18
GNAL	-0.19	0.34	-10000	0	-0.8	244	244
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.005	0.086	-10000	0	-0.54	25	25
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	49	49
HBEGF	-0.067	0.19	-10000	0	-0.45	171	171
cAMP biosynthetic process	-0.19	0.26	-10000	0	-0.51	366	366
SRC	-0.049	0.2	-10000	0	-0.45	162	162
PI3K	-0.006	0.061	-10000	0	-0.61	10	10
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.077	0.18	-10000	0	-0.47	180	180
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.52	228	228
Gs family/GTP	-0.2	0.26	-10000	0	-0.52	366	366
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.013	-10000	0	-10000	0	0
vasodilation	-0.054	0.21	-10000	0	-0.52	161	161
mol:DAG	-0.03	0.15	-10000	0	-0.59	34	34
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.45	367	367
MSN	-0.027	0.15	-10000	0	-0.4	30	30
Gq family/GTP	-0.037	0.096	-10000	0	-0.68	13	13
mol:PI-3-4-5-P3	-0.095	0.31	-10000	0	-0.82	151	151
NRAS	-0.001	0.013	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.054	0.21	0.52	161	-10000	0	161
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.078	0.19	-10000	0	-0.5	172	172
NOS3	-0.063	0.23	-10000	0	-0.58	161	161
GNA11	-0.002	0.036	-10000	0	-0.8	2	2
MAPKKK cascade	-0.065	0.26	-10000	0	-0.64	166	166
E2/ER alpha (dimer)/PELP1/Src	-0.095	0.22	-10000	0	-0.57	160	160
ruffle organization	-0.023	0.14	-10000	0	-0.37	30	30
ROCK2	-0.074	0.14	-10000	0	-0.38	175	175
GNA14	-0.014	0.088	-10000	0	-0.45	31	31
GNA15	-0.003	0.034	-10000	0	-0.35	8	8
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.092	0.2	-10000	0	-0.48	169	169
MMP2	-0.042	0.19	-10000	0	-0.43	169	169

×

Neurotrophic factor-mediated Trk receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.11	0.12	-10000	0	-0.33	89	89
NT3 (dimer)/TRKC	-0.31	0.37	-10000	0	-0.7	439	439
NT3 (dimer)/TRKB	-0.51	0.45	-10000	0	-0.8	656	656
SHC/Grb2/SOS1/GAB1/PI3K	-0.003	0.032	-10000	0	-0.32	10	10
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.07	0.22	-10000	0	-0.69	104	104
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DYNLT1	0	0.009	-10000	0	-0.29	1	1
NTRK1	-0.01	0.067	-10000	0	-0.36	29	29
NTRK2	-0.42	0.4	-10000	0	-0.8	539	539
NTRK3	-0.28	0.38	-10000	0	-0.8	354	354
NT-4/5 (dimer)/TRKB	-0.6	0.49	-10000	0	-0.87	705	705
neuron apoptosis	0.24	0.24	0.59	287	-10000	0	287
SHC 2-3/Grb2	-0.27	0.28	-10000	0	-0.66	287	287
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.25	0.29	-10000	0	-0.68	271	271
SHC3	-0.25	0.28	-10000	0	-0.66	276	276
STAT3 (dimer)	-0.005	0.028	-10000	0	-0.38	3	3
NT3 (dimer)/TRKA	-0.26	0.32	-10000	0	-0.61	417	417
RIN/GDP	-0.069	0.12	-10000	0	-0.28	58	58
GIPC1	-0.001	0.015	-10000	0	-10000	0	0
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
DNAJA3	-0.14	0.21	-10000	0	-0.44	321	321
RIN/GTP	0	0.009	-10000	0	-10000	0	0
CCND1	0.019	0.069	-10000	0	-1	3	3
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.28	0.38	-10000	0	-0.8	356	356
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.027	0.11	-10000	0	-0.56	35	35
TRKA/NEDD4-2	-0.007	0.051	-10000	0	-0.61	5	5
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.014	0.099	-10000	0	-0.64	22	22
HRAS	-0.002	0.025	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.004	0.044	-10000	0	-0.38	11	11
RIT2	-0.001	0.013	-10000	0	-0.29	2	2
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.028	-10000	0	-10000	0	0
DNM1	-0.006	0.067	-10000	0	-0.8	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.14	0.2	-10000	0	-0.42	321	321
mol:GDP	-0.11	0.18	-10000	0	-0.37	207	207
NGF (dimer)	-0.014	0.099	-10000	0	-0.64	22	22
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.065	0.12	-10000	0	-0.29	51	51
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
BDNF (dimer)/TRKB	-0.32	0.3	-10000	0	-0.58	565	565
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0.004	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.29	-10000	0	-0.76	176	176
RAP1/GDP	-0.074	0.085	-10000	0	-0.25	18	18
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.07	0.22	-10000	0	-0.69	104	104
ubiquitin-dependent protein catabolic process	-0.015	0.076	-10000	0	-0.53	20	20
Schwann cell development	-0.06	0.044	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.012	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.001	0.012	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.44	0.39	-10000	0	-0.87	388	388
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.11	0.099	-10000	0	-10000	0	0
STAT3	-0.005	0.028	-10000	0	-0.38	3	3
axon guidance	-0.41	0.35	-10000	0	-0.81	388	388
MAPK3	0.005	0.1	-10000	0	-0.51	35	35
MAPK1	0.005	0.1	-10000	0	-0.51	35	35
CDC42/GDP	-0.065	0.12	-10000	0	-0.29	49	49
NTF3	-0.13	0.29	-10000	0	-0.76	176	176
NTF4	-0.28	0.38	-10000	0	-0.8	356	356
NGF (dimer)/TRKA/FAIM	-0.014	0.075	-10000	0	-0.53	19	19
PI3K	-0.006	0.061	-10000	0	-0.61	10	10
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.16	0.22	-10000	0	-0.46	325	325
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.25	0.34	-10000	0	-0.61	441	441
RGS19	-0.001	0.013	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.083	-10000	0	-10000	0	0
Rac1/GDP	-0.065	0.12	-10000	0	-0.29	50	50
NGF (dimer)/TRKA/GRIT	-0.015	0.077	-10000	0	-0.54	19	19
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.64	22	22
NGF (dimer)/TRKA/NEDD4-2	-0.015	0.077	-10000	0	-0.53	20	20
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.25	0.37	-10000	0	-0.8	321	321
NGF (dimer)/TRKA/GIPC/GAIP	-0.009	0.054	-10000	0	-0.34	25	25
RAS family/GTP/PI3K	-0.004	0.034	-10000	0	-0.34	10	10
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.01	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
MAPKKK cascade	-0.065	0.12	-10000	0	-0.82	19	19
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.047	-10000	0	-0.61	4	4
SQSTM1	0	0.009	-10000	0	-0.29	1	1
BDNF (dimer)/TRKB/GIPC	-0.29	0.28	-10000	0	-0.53	565	565
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.012	0.064	-10000	0	-0.45	20	20
MATK	-0.022	0.11	-10000	0	-0.49	45	45
NEDD4L	-0.001	0.025	-10000	0	-0.8	1	1
RAS family/GDP	-0.067	0.08	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.15	0.22	-10000	0	-0.46	328	328
Rac1/GTP	-0.13	0.14	-10000	0	-0.34	247	247
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.003	0.05	-10000	0	-0.8	4	4
Jak2/Leptin Receptor	-0.16	0.24	-10000	0	-0.53	279	279
PTP1B/AKT1	-0.072	0.11	-10000	0	-0.34	109	109
FYN	-0.002	0.036	-10000	0	-0.8	2	2
p210 bcr-abl/PTP1B	-0.074	0.13	-10000	0	-0.38	117	117
EGFR	-0.3	0.39	-10000	0	-0.81	384	384
EGF/EGFR	-0.3	0.31	-10000	0	-0.58	526	526
CSF1	-0.006	0.066	-10000	0	-0.8	7	7
AKT1	0	0.001	-10000	0	-10000	0	0
INSR	0	0.009	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.099	0.12	-10000	0	-0.38	114	114
Insulin Receptor/Insulin	-0.051	0.082	-10000	0	-0.42	19	19
HCK	-0.003	0.031	-10000	0	-0.29	12	12
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.062	0.13	-10000	0	-0.37	110	110
EGF	-0.17	0.33	-10000	0	-0.81	214	214
YES1	-0.001	0.025	-10000	0	-0.8	1	1
CAV1	-0.18	0.24	-10000	0	-0.5	282	282
TXN	0	0.016	-10000	0	-0.29	1	1
PTP1B/IRS1/GRB2	-0.089	0.15	-10000	0	-0.41	141	141
cell migration	0.074	0.13	0.38	117	-10000	0	117
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.005	0.066	-10000	0	-0.52	13	13
ITGA2B	-0.017	0.077	-10000	0	-0.32	57	57
CSF1R	-0.001	0.027	-10000	0	-0.54	2	2
Prolactin Receptor/Prolactin	-0.006	0.054	-10000	0	-0.62	6	6
FGR	0	0.009	-10000	0	-0.29	1	1
PTP1B/p130 Cas	-0.077	0.12	-10000	0	-0.37	107	107
Crk/p130 Cas	-0.071	0.11	-10000	0	-0.44	40	40
DOK1	-0.048	0.12	-10000	0	-0.33	101	101
JAK2	-0.043	0.08	-10000	0	-0.33	25	25
Jak2/Leptin Receptor/Leptin	-0.37	0.19	-10000	0	-0.44	831	831
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
PTPN1	-0.074	0.13	-10000	0	-0.38	117	117
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.054	0.12	-10000	0	-0.8	2	2
SRC	-0.014	0.048	-10000	0	-10000	0	0
ITGB3	-0.029	0.15	-10000	0	-0.75	39	39
CAT1/PTP1B	-0.086	0.17	-10000	0	-0.37	182	182
CAPN1	0	0.009	-10000	0	-0.29	1	1
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.044	0.092	-10000	0	-0.55	17	17
mol:H2O2	-0.006	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.33	0.16	-10000	0	-0.43	568	568
negative regulation of transcription	-0.042	0.079	-10000	0	-0.33	25	25
FCGR2A	0	0.009	-10000	0	-0.29	1	1
FER	-0.009	0.088	-10000	0	-0.81	12	12
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.63	38	38
BLK	-0.041	0.11	-10000	0	-0.3	142	142
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0.001	0.003	-10000	0	-10000	0	0
LEPR	-0.21	0.36	-10000	0	-0.8	272	272
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-10000	0	0
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.03	0.13	-10000	0	-0.37	36	36
PRL	-0.004	0.033	-10000	0	-0.29	13	13
SOCS3	0.017	0.12	-10000	0	-1.5	6	6
SPRY2	-0.095	0.26	-10000	0	-0.81	120	120
Insulin Receptor/Insulin/IRS1	-0.023	0.11	-10000	0	-0.55	43	43
CSF1/CSF1R	-0.074	0.12	-10000	0	-0.36	116	116
Ras protein signal transduction	0.038	0.036	-10000	0	-10000	0	0
IRS1	-0.034	0.16	-10000	0	-0.8	43	43
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.65	0.32	-10000	0	-0.8	823	823
STAT5B	-0.06	0.11	-10000	0	-0.32	114	114
STAT5A	-0.061	0.11	-10000	0	-0.32	117	117
GRB2	0	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.079	0.12	-10000	0	-0.38	112	112
CSN2	0.019	0.034	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
LAT	-0.015	0.054	-10000	0	-0.58	2	2
YBX1	-0.001	0.014	-10000	0	-0.28	1	1
LCK	-0.02	0.1	-10000	0	-0.42	49	49
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.004	0.046	-10000	0	-0.38	12	12

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.073	0.066	-9999	-0.62	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.019	0.017	-9999	-10000	0	0
AURKB	-0.16	0.14	-9999	-0.29	586	586
AURKC	-0.004	0.041	-9999	-0.32	14	14

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.062	-9999	-0.57	10	10
alphaM/beta2 Integrin/GPIbA	-0.024	0.059	-9999	-0.53	9	9
alphaM/beta2 Integrin/proMMP-9	-0.079	0.08	-9999	-0.38	8	8
PLAUR	-0.02	0.074	-9999	-0.29	73	73
HMGB1	-0.013	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.017	0.028	-9999	-10000	0	0
AGER	-0.015	0.041	-9999	-0.86	2	2
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.074	0.097	-9999	-0.7	2	2
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.29	437	437
CYR61	-0.044	0.18	-9999	-0.8	56	56
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.056	0.11	-9999	-0.53	20	20
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.34	-9999	-0.8	238	238
MYH2	-0.067	0.16	-9999	-0.36	196	196
MST1R	-0.011	0.087	-9999	-0.57	20	20
leukocyte activation during inflammatory response	-0.3	0.22	-9999	-0.48	633	633
APOB	-0.5	0.39	-9999	-0.8	633	633
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.079	-9999	-0.8	10	10
JAM3	-0.006	0.066	-9999	-0.8	7	7
GP1BA	-0.012	0.079	-9999	-0.4	31	31
alphaM/beta2 Integrin/CTGF	-0.024	0.07	-9999	-0.59	13	13
alphaM/beta2 Integrin	-0.07	0.13	-9999	-0.3	186	186
JAM3 homodimer	-0.006	0.066	-9999	-0.8	7	7
ICAM2	-0.004	0.056	-9999	-0.8	5	5
ICAM1	-0.004	0.034	-9999	-0.29	15	15
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.059	0.14	-9999	-0.3	186	186
cell adhesion	-0.024	0.058	-9999	-0.53	9	9
NFKB1	-0.14	0.18	-9999	-0.66	14	14
THY1	-0.002	0.024	-9999	-0.29	7	7
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.34	0.26	-9999	-0.55	633	633
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.11	-9999	-0.55	42	42
IL6	-0.3	0.48	-9999	-0.94	373	373
ITGB2	-0.017	0.035	-9999	-0.3	12	12
elevation of cytosolic calcium ion concentration	-0.024	0.047	-9999	-0.39	1	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.044	0.13	-9999	-0.55	61	61
JAM2	-0.046	0.19	-9999	-0.8	59	59
alphaM/beta2 Integrin/ICAM1	-0.022	0.084	-9999	-0.54	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.032	-9999	-10000	0	0
RhoA/GTP	-0.084	0.16	-9999	-0.37	213	213
positive regulation of phagocytosis	-0.048	0.088	-9999	-0.46	17	17
Ron/MSP	-0.017	0.1	-9999	-0.67	22	22
alphaM/beta2 Integrin/uPAR/uPA	-0.024	0.048	-9999	-0.39	1	1
alphaM/beta2 Integrin/uPAR	-0.027	0.045	-9999	-0.38	2	2
PLAU	-0.008	0.047	-9999	-0.29	28	28
PLAT	-0.028	0.15	-9999	-0.76	38	38
actin filament polymerization	-0.064	0.16	-9999	-0.34	196	196
MST1	-0.012	0.092	-9999	-0.66	18	18
alphaM/beta2 Integrin/lipoprotein(a)	-0.3	0.23	-9999	-0.48	633	633
TNF	-0.089	0.22	-9999	-0.96	18	18
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.021	0.035	-9999	-10000	0	0
fibrinolysis	-0.019	0.032	-9999	-10000	0	0
HCK	-0.003	0.031	-9999	-0.29	12	12
dendritic cell antigen processing and presentation	-0.059	0.14	-9999	-0.3	186	186
VTN	-0.024	0.091	-9999	-0.32	76	76
alphaM/beta2 Integrin/CYR61	-0.047	0.13	-9999	-0.58	56	56
LPA	-0.001	0.02	-9999	-10000	0	0
LRP1	-0.009	0.083	-9999	-0.8	11	11
cell migration	-0.069	0.082	-9999	-0.51	12	12
FN1	-0.11	0.14	-9999	-0.29	404	404
alphaM/beta2 Integrin/Thy1	-0.018	0.03	-9999	-10000	0	0
MPO	-0.053	0.2	-9999	-0.78	69	69
KNG1	-0.004	0.034	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.063	0.16	-9999	-0.37	149	149
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.018	-9999	-0.29	4	4
CTGF	-0.011	0.091	-9999	-0.73	15	15
alphaM/beta2 Integrin/Hck	-0.019	0.033	-9999	-0.32	2	2
ITGAM	-0.015	0.028	-9999	-0.34	2	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.21	-9999	-0.51	238	238
HP	-0.16	0.31	-9999	-0.72	225	225
leukocyte adhesion	-0.076	0.13	-9999	-0.6	41	41
SELP	-0.19	0.34	-9999	-0.8	238	238

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.023	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.039	-9999	-0.3	2	2
PDE6G/GNAT1/GTP	-0.008	0.035	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.034	-9999	-10000	0	0
GRK1	-0.003	0.028	-9999	-0.29	10	10
CNG Channel	-0.14	0.2	-9999	-0.48	122	122
mol:Na +	-0.13	0.19	-9999	-0.42	298	298
mol:ADP	-0.003	0.028	-9999	-0.28	10	10
RGS9-1/Gbeta5/R9AP	-0.064	0.16	-9999	-0.54	104	104
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.14	0.2	-9999	-0.44	298	298
CNGB1	-0.015	0.063	-9999	-0.29	52	52
RDH5	-0.48	0.39	-9999	-0.8	604	604
SAG	-0.015	0.063	-9999	-0.29	53	53
mol:Ca2+	-0.13	0.18	-9999	-0.42	178	178
Na + (4 Units)	-0.12	0.18	-9999	-0.41	178	178
RGS9	-0.086	0.24	-9999	-0.74	118	118
GNB1/GNGT1	-0.029	0.067	-9999	-10000	0	0
GNAT1/GDP	-0.057	0.14	-9999	-0.47	104	104
GUCY2D	-0.007	0.057	-9999	-0.36	20	20
GNGT1	-0.046	0.1	-9999	-0.29	164	164
GUCY2F	-0.001	0.013	-9999	-0.29	2	2
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.018	0.07	-9999	-0.46	20	20
mol:11-cis-retinal	-0.48	0.39	-9999	-0.8	604	604
mol:cGMP	-0.01	0.048	-9999	-0.46	8	8
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.37	0.3	-9999	-0.62	604	604
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.23	0.36	-9999	-0.79	299	299
Metarhodopsin II	-0.003	0.021	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.011	0.051	-9999	-0.49	8	8
RGS9BP	-0.017	0.068	-9999	-0.29	61	61
Metarhodopsin II/Transducin	-0.009	0.019	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.043	-9999	-0.5	5	5
PDE6A/B	-0.016	0.089	-9999	-0.61	20	20
mol:Pi	-0.064	0.16	-9999	-0.54	104	104
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.022	0.049	-9999	-10000	0	0
PDE6B	-0.016	0.11	-9999	-0.8	20	20
PDE6A	-0.006	0.042	-9999	-10000	0	0
PDE6G	-0.011	0.056	-9999	-0.29	41	41
RHO	-0.004	0.033	-9999	-0.29	14	14
PDE6	-0.064	0.15	-9999	-0.45	120	120
GUCA1A	-0.011	0.055	-9999	-0.29	39	39
GC2/GCAP Family	-0.008	0.043	-9999	-0.5	5	5
GUCA1C	0	0.009	-9999	-0.29	1	1
GUCA1B	-0.004	0.056	-9999	-0.8	5	5

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.043	-9999	-0.61	4	4
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.55	423	423
PTK2	-0.091	0.2	-9999	-0.66	43	43
IGF1R	-0.021	0.12	-9999	-0.61	35	35
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.093	-9999	-0.8	13	13
SRC	0	0.009	-9999	-0.29	1	1
CDKN1B	-0.086	0.12	-9999	-0.87	8	8
VEGFA	-0.003	0.03	-9999	-10000	0	0
ILK	-0.084	0.11	-9999	-0.76	5	5
ROCK1	-0.001	0.025	-9999	-0.8	1	1
AKT1	-0.074	0.095	-9999	-0.71	5	5
PTK2B	-0.018	0.093	-9999	-0.48	36	36
alphaV/beta3 Integrin/JAM-A	-0.2	0.25	-9999	-0.48	426	426
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.02	0.098	-9999	-0.53	35	35
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.26	-9999	-0.56	248	248
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.012	0.059	-9999	-0.42	8	8
alphaV/beta3 Integrin/Syndecan-1	-0.029	0.1	-9999	-0.54	36	36
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.33	0.36	-9999	-0.64	500	500
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Osteopontin	-0.056	0.11	-9999	-0.55	35	35
RPS6KB1	-0.3	0.32	-9999	-0.7	324	324
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.33	0.39	-9999	-0.77	423	423
GPR124	-0.009	0.087	-9999	-0.8	12	12
MAPK1	-0.33	0.39	-9999	-0.77	423	423
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
alphaV/beta3 Integrin/Tumstatin	-0.11	0.22	-9999	-0.54	213	213
cell adhesion	-0.024	0.11	-9999	-0.51	45	45
ANGPTL3	-0.001	0.02	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.004	0.036	-9999	-0.53	4	4
IGF-1R heterotetramer	-0.021	0.12	-9999	-0.61	35	35
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.034	0.16	-9999	-0.8	43	43
ITGB3	-0.029	0.15	-9999	-0.75	39	39
IGF1	-0.18	0.33	-9999	-0.8	225	225
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.024	0.12	-9999	-0.6	41	41
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.025	-9999	-0.8	1	1
alphaV/beta3 Integrin/CD47	-0.019	0.098	-9999	-0.53	36	36
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.05	0.18	-9999	-0.67	72	72
CSF1	-0.006	0.066	-9999	-0.8	7	7
PIK3C2A	-0.085	0.11	-9999	-0.81	6	6
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.6	65	65
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.02	0.1	-9999	-0.52	36	36
FAK1/Vinculin	-0.066	0.16	-9999	-0.5	40	40
alphaV beta3/Integrin/ppsTEM5	-0.025	0.12	-9999	-0.6	41	41
RHOA	0	0	-9999	-10000	0	0
VTN	-0.024	0.091	-9999	-0.32	76	76
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.32	0.39	-9999	-0.8	409	409
F11R	-0.23	0.31	-9999	-0.61	409	409
alphaV/beta3 Integrin/Lactadherin	-0.026	0.12	-9999	-0.57	44	44
alphaV/beta3 Integrin/TGFBR2	-0.04	0.17	-9999	-0.67	60	60
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.04	-9999	-0.48	7	7
HSP90AA1	0	0.009	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.017	0.089	-9999	-0.49	35	35
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.14	-9999	-0.29	404	404
alphaV/beta3 Integrin/Pyk2	-0.019	0.094	-9999	-0.49	36	36
SDC1	-0.021	0.078	-9999	-0.29	74	74
VAV3	-0.007	0.052	-9999	-0.45	13	13
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.034	0.16	-9999	-0.8	43	43
FAK1/Paxillin	-0.066	0.16	-9999	-0.5	40	40
cell migration	-0.052	0.15	-9999	-0.44	40	40
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.23	-9999	-0.59	92	92
SPP1	-0.076	0.13	-9999	-0.29	271	271
KDR	-0.003	0.05	-9999	-0.8	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.15	0.31	-9999	-0.79	188	188
angiogenesis	-0.3	0.39	-9999	-0.74	425	425
Rac1/GTP	-0.007	0.047	-9999	-0.41	13	13
EDIL3	-0.05	0.19	-9999	-0.8	58	58
cell proliferation	-0.04	0.17	-9999	-0.67	60	60

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.063	0.22	-9999	-0.63	60	60
CRP	-0.067	0.22	-9999	-0.68	40	40
cell cycle arrest	-0.081	0.25	-9999	-0.72	67	67
TIMP1	-0.06	0.21	-9999	-0.59	49	49
IL6ST	-0.082	0.26	-9999	-0.8	120	120
Rac1/GDP	-0.13	0.23	-9999	-0.68	86	86
AP1	-0.13	0.24	-9999	-0.5	245	245
GAB2	0.004	0.045	-9999	-0.38	11	11
TNFSF11	-0.072	0.22	-9999	-0.66	48	48
HSP90B1	0.016	0.047	-9999	-10000	0	0
GAB1	0	0.002	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.73	88	88
AKT1	0.038	0.04	-9999	-10000	0	0
FOXO1	0.048	0.057	-9999	-0.42	10	10
MAP2K6	-0.15	0.26	-9999	-0.71	103	103
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.085	0.23	-9999	-0.65	83	83
MITF	-0.14	0.26	-9999	-0.62	126	126
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.014	0.13	-9999	-1.5	7	7
CEBPB	0.016	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.056	0.084	-9999	-1	2	2
STAT3	-0.089	0.26	-9999	-0.79	67	67
STAT1	-0.013	0.022	-9999	-10000	0	0
CEBPD	-0.064	0.23	-9999	-0.65	60	60
PIK3CA	0.012	0.009	-9999	-0.28	1	1
PI3K	-0.006	0.061	-9999	-0.61	10	10
JUN	-0.007	0.075	-9999	-0.8	9	9
PIAS3/MITF	-0.16	0.22	-9999	-0.68	93	93
MAPK11	-0.13	0.25	-9999	-0.75	88	88
STAT3 (dimer)/FOXO1	-0.033	0.22	-9999	-0.6	61	61
GRB2/SOS1/GAB family	-0.14	0.2	-9999	-0.75	63	63
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.16	0.26	-9999	-0.47	252	252
GRB2	0	0.009	-9999	-10000	0	0
JAK2	-0.001	0.025	-9999	-0.8	1	1
LBP	-0.23	0.45	-9999	-0.97	246	246
PIK3R1	0.003	0.08	-9999	-0.8	10	10
JAK1	0.002	0.026	-9999	-0.8	1	1
MYC	-0.076	0.26	-9999	-0.86	55	55
FGG	-0.072	0.22	-9999	-0.68	43	43
macrophage differentiation	-0.081	0.25	-9999	-0.72	67	67
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.28	-9999	-0.51	462	462
JUNB	-0.061	0.21	-9999	-0.65	42	42
FOS	-0.24	0.37	-9999	-0.8	307	307
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.15	0.27	-9999	-0.49	251	251
STAT1/PIAS1	-0.14	0.22	-9999	-0.65	94	94
GRB2/SOS1/GAB family/SHP2/PI3K	-0.002	0.031	-9999	-0.33	1	1
STAT3 (dimer)	-0.084	0.26	-9999	-0.76	67	67
PRKCD	-0.059	0.22	-9999	-0.62	75	75
IL6R	-0.028	0.15	-9999	-0.8	39	39
SOCS3	-0.12	0.24	-9999	-0.76	79	79
gp130 (dimer)/JAK1/JAK1/LMO4	-0.055	0.18	-9999	-0.53	123	123
Rac1/GTP	-0.15	0.21	-9999	-0.68	87	87
HCK	-0.003	0.031	-9999	-0.29	12	12
MAPKKK cascade	-0.005	0.085	-9999	-1	2	2
bone resorption	-0.068	0.21	-9999	-0.61	54	54
IRF1	-0.063	0.22	-9999	-0.64	54	54
mol:GDP	-0.13	0.25	-9999	-0.67	100	100
SOS1	0	0.003	-9999	-10000	0	0
VAV1	-0.13	0.26	-9999	-0.69	100	100
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.17	0.25	-9999	-0.82	84	84
PTPN11	-0.013	0.02	-9999	-10000	0	0
IL6/IL6RA	-0.24	0.32	-9999	-0.64	390	390
gp130 (dimer)/TYK2/TYK2/LMO4	-0.057	0.18	-9999	-0.53	123	123
gp130 (dimer)/JAK2/JAK2/LMO4	-0.058	0.18	-9999	-0.53	123	123
IL6	-0.28	0.39	-9999	-0.8	373	373
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.003	0.026	-9999	-0.81	1	1
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-9999	-0.41	461	461
LMO4	0.009	0.05	-9999	-0.54	6	6
STAT3 (dimer)/PIAS3	-0.15	0.21	-9999	-0.78	67	67
MCL1	0.051	0.033	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

Figure S40. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S40. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.036	0.16	-9999	-0.31	255	255
RXRs/LXRs/DNA/Oxysterols	-0.016	0.15	-9999	-0.43	33	33
MED1	-0.007	0.043	-9999	-0.29	24	24
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.022	0.091	-9999	-0.36	62	62
RXRs/NUR77	-0.16	0.24	-9999	-0.51	308	308
RXRs/PPAR	-0.13	0.23	-9999	-0.38	420	420
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.007	0.051	-9999	-0.46	12	12
RARA	-0.004	0.033	-9999	-10000	0	0
NCOA1	-0.001	0.025	-9999	-0.8	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.007	0.051	-9999	-0.46	12	12
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.022	0.087	-9999	-0.35	62	62
THRA	-0.001	0.025	-9999	-0.8	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.2	-9999	-0.48	252	252
NR1H4	-0.003	0.027	-9999	-0.29	9	9
RXRs/LXRs/DNA	-0.11	0.19	-9999	-0.43	252	252
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.19	-9999	-0.45	252	252
NR4A1	-0.064	0.22	-9999	-0.8	81	81
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.044	0.13	-9999	-0.27	252	252
RXRG	-0.19	0.35	-9999	-0.8	252	252
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.016	0.007	-9999	-10000	0	0
THRB	-0.043	0.18	-9999	-0.8	54	54
PPARG	-0.19	0.34	-9999	-0.8	238	238
PPARD	0	0	-9999	-10000	0	0
TNF	-0.018	0.2	-9999	-1.2	15	15
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.016	0.15	-9999	-0.43	33	33
PPARA	-0.005	0.061	-9999	-0.8	6	6
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.009	0.087	-9999	-0.8	12	12
RXRs/NUR77/BCL2	-0.12	0.19	-9999	-0.38	330	330
SREBF1	-0.006	0.14	-9999	-0.63	8	8
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-9999	-0.48	252	252
ABCA1	-0.01	0.16	-9999	-1	10	10
RARs/THRs	-0.031	0.12	-9999	-0.48	62	62
RXRs/FXR	-0.12	0.21	-9999	-0.48	252	252
BCL2	-0.028	0.15	-9999	-0.8	36	36

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.055	0.16	-9999	-0.54	103	103
EFNA5	-0.081	0.24	-9999	-0.8	103	103
FYN	-0.051	0.15	-9999	-0.49	104	104
neuron projection morphogenesis	-0.055	0.16	-9999	-0.54	103	103
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.055	0.16	-9999	-0.54	103	103
EPHA5	-0.001	0.018	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.018	0.094	-9999	-0.52	31	31
NF kappa B1 p50/RelA/I kappa B alpha	-0.044	0.11	-9999	-0.48	5	5
AP1	-0.19	0.26	-9999	-0.48	396	396
mol:PIP3	-0.2	0.25	-9999	-0.46	433	433
AKT1	-0.014	0.073	-9999	-0.59	7	7
PTK2B	0.014	0.061	-9999	-0.3	22	22
RHOA	0.029	0.026	-9999	-0.23	1	1
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.007	0.13	-9999	-0.35	121	121
MAGI3	-0.001	0.025	-9999	-0.8	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.062	0.15	-9999	-0.42	145	145
HRAS/GDP	-0.002	0.017	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.018	0.15	-9999	-0.41	109	109
NF kappa B1 p50/RelA	-0.053	0.14	-9999	-0.64	9	9
endothelial cell migration	0.008	0.12	-9999	-0.65	29	29
ADCY4	-0.001	0.15	-9999	-0.64	35	35
ADCY5	-0.069	0.19	-9999	-0.57	80	80
ADCY6	0.008	0.12	-9999	-0.61	27	27
ADCY7	0.008	0.12	-9999	-0.61	27	27
ADCY1	0	0.14	-9999	-0.64	33	33
ADCY2	-0.011	0.16	-9999	-0.64	39	39
ADCY3	0.008	0.12	-9999	-0.61	27	27
ADCY8	0.005	0.13	-9999	-0.59	29	29
ADCY9	0.008	0.12	-9999	-0.61	27	27
GSK3B	0.022	0.058	-9999	-0.36	9	9
arachidonic acid secretion	0.012	0.12	-9999	-0.44	53	53
GNG2	-0.009	0.087	-9999	-0.8	12	12
TRIP6	-0.001	0.017	-9999	-0.52	1	1
GNAO1	-0.006	0.13	-9999	-0.53	51	51
HRAS	-0.002	0.025	-9999	-10000	0	0
NFKBIA	-0.004	0.15	-9999	-0.4	121	121
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0	0.03	-9999	-0.94	1	1
JUN	-0.007	0.075	-9999	-0.8	9	9
LPA/LPA2/NHERF2	-0.002	0.015	-9999	-10000	0	0
TIAM1	0	0.035	-9999	-1.1	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:IP3	-0.008	0.13	-9999	-0.36	121	121
PLCB3	0.025	0.017	-9999	-10000	0	0
FOS	-0.24	0.37	-9999	-0.8	307	307
positive regulation of mitosis	0.012	0.12	-9999	-0.44	53	53
LPA/LPA1-2-3	-0.074	0.17	-9999	-0.5	137	137
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.002	0.1	-9999	-0.39	21	21
GNAZ	0.009	0.1	-9999	-0.49	37	37
EGFR/PI3K-beta/Gab1	-0.21	0.26	-9999	-0.48	433	433
positive regulation of dendritic cell cytokine production	-0.073	0.17	-9999	-0.49	137	137
LPA/LPA2/MAGI-3	-0.002	0.02	-9999	-0.53	1	1
ARHGEF1	-0.01	0.068	-9999	-0.45	20	20
GNAI2	0.014	0.085	-9999	-0.47	29	29
GNAI3	0.014	0.085	-9999	-0.47	29	29
GNAI1	-0.013	0.15	-9999	-0.55	71	71
LPA/LPA3	-0.082	0.2	-9999	-0.62	121	121
LPA/LPA2	-0.002	0.016	-9999	-10000	0	0
LPA/LPA1	-0.016	0.094	-9999	-0.55	29	29
HB-EGF/EGFR	-0.26	0.26	-9999	-0.58	384	384
HBEGF	-0.066	0.1	-9999	-0.61	3	3
mol:DAG	-0.008	0.13	-9999	-0.36	121	121
cAMP biosynthetic process	-0.009	0.15	-9999	-0.56	51	51
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
GNB1	0	0	-9999	-10000	0	0
LYN	-0.004	0.15	-9999	-0.4	121	121
GNAQ	-0.054	0.14	-9999	-0.41	123	123
LPAR2	-0.001	0.015	-9999	-10000	0	0
LPAR3	-0.11	0.26	-9999	-0.68	160	160
LPAR1	-0.017	0.11	-9999	-0.8	20	20
IL8	-0.19	0.23	-9999	-0.44	404	404
PTK2	-0.068	0.16	-9999	-0.46	137	137
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.062	0.15	-9999	-0.42	145	145
EGFR	-0.3	0.39	-9999	-0.8	384	384
PLCG1	-0.034	0.15	-9999	-0.43	121	121
PLD2	-0.068	0.16	-9999	-0.46	137	137
G12/G13	-0.012	0.073	-9999	-0.49	20	20
PI3K-beta	-0.017	0.086	-9999	-0.43	37	37
cell migration	-0.022	0.054	-9999	-0.25	6	6
SLC9A3R2	-0.001	0.018	-9999	-10000	0	0
PXN	0.002	0.1	-9999	-0.4	21	21
HRAS/GTP	-0.033	0.12	-9999	-0.46	53	53
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.29	437	437
PRKCE	-0.001	0.025	-9999	-0.8	1	1
PRKCD	0	0.13	-9999	-0.55	2	2
Gi(beta/gamma)	-0.034	0.12	-9999	-0.59	34	34
mol:LPA	-0.002	0.02	-9999	-0.22	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.056	0.14	-9999	-0.64	10	10
MAPKKK cascade	0.012	0.12	-9999	-0.44	53	53
contractile ring contraction involved in cytokinesis	0.029	0.026	-9999	-0.23	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.059	0.14	-9999	-0.43	129	129
GNA15	-0.054	0.13	-9999	-0.41	122	122
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.019	0.15	-9999	-0.43	109	109
GNA11	-0.054	0.14	-9999	-0.41	123	123
Rac1/GTP	0	0.032	-9999	-1	1	1
MMP2	0.008	0.12	-9999	-0.66	29	29

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.094	0.2	0.64	108	-10000	0	108
KIRREL	-0.084	0.25	-10000	0	-0.81	108	108
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.094	0.2	-10000	0	-0.64	108	108
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.068	0.15	-10000	0	-0.49	108	108
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.042	0.11	-10000	0	-0.36	108	108
FYN	-0.063	0.14	-10000	0	-0.47	108	108
mol:Ca2+	-0.067	0.15	-10000	0	-0.49	108	108
mol:DAG	-0.068	0.15	-10000	0	-0.49	108	108
NPHS2	-0.008	0.029	-10000	0	-0.28	4	4
mol:IP3	-0.068	0.15	-10000	0	-0.49	108	108
regulation of endocytosis	-0.035	0.14	-10000	0	-0.44	108	108
Nephrin/NEPH1/podocin/Cholesterol	-0.07	0.15	-10000	0	-0.5	108	108
establishment of cell polarity	-0.094	0.2	-10000	0	-0.64	108	108
Nephrin/NEPH1/podocin/NCK1-2	-0.055	0.14	-10000	0	-0.45	108	108
Nephrin/NEPH1/beta Arrestin2	-0.036	0.14	-10000	0	-0.44	108	108
NPHS1	-0.05	0.11	-10000	0	-0.36	16	16
Nephrin/NEPH1/podocin	-0.064	0.15	-10000	0	-0.47	108	108
TJP1	-0.001	0.025	-10000	0	-0.8	1	1
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.068	0.15	-10000	0	-0.49	108	108
CD2AP	0	0.009	-10000	0	-0.29	1	1
Nephrin/NEPH1/podocin/GRB2	-0.068	0.15	-10000	0	-0.49	108	108
GRB2	0	0.009	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.073	0.17	-10000	0	-0.51	116	116
cytoskeleton organization	-0.053	0.14	-10000	0	-0.46	108	108
Nephrin/NEPH1	-0.068	0.15	-10000	0	-0.48	108	108
Nephrin/NEPH1/ZO-1	-0.074	0.16	-10000	0	-0.53	108	108

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.027	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.18	0.2	-9999	-0.41	448	448
Syndecan-3/Neurocan	-0.007	0.027	-9999	-10000	0	0
POMC	-0.023	0.12	-9999	-0.47	50	50
EGFR	-0.3	0.39	-9999	-0.8	384	384
Syndecan-3/EGFR	-0.17	0.22	-9999	-0.45	379	379
AGRP	-0.003	0.028	-9999	-10000	0	0
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.009	-9999	-0.29	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.025	-9999	-0.8	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.071	-9999	-0.29	67	67
long-term memory	-0.002	0.021	-9999	-0.42	2	2
Syndecan-3/IL8	-0.015	0.067	-9999	-0.45	20	20
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.8	2	2
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.003	0.031	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PTN	-0.35	0.4	-9999	-0.8	450	450
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.18	0.2	-9999	-0.4	448	448
Syndecan-3/AgRP	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.015	-9999	-10000	0	0
Fyn/Cortactin	-0.003	0.032	-9999	-0.61	2	2
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.015	0.066	-9999	-0.44	20	20
IL8	-0.033	0.13	-9999	-0.41	81	81
Syndecan-3/Fyn/Cortactin	-0.002	0.021	-9999	-0.43	2	2
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.019	0.089	-9999	-0.59	20	20
Gamma Secretase	-0.001	0.014	-9999	-0.45	1	1

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.055	0.3	-10000	0	-0.81	124	124
IHH	-0.014	0.08	-10000	0	-0.4	7	7
SHH Np/Cholesterol/GAS1	-0.03	0.12	-10000	0	-0.5	57	57
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.03	0.12	0.5	57	-10000	0	57
SMO/beta Arrestin2	-0.076	0.23	-10000	0	-0.8	85	85
SMO	-0.037	0.26	-10000	0	-0.84	88	88
AKT1	0.007	0.11	-10000	0	-0.42	24	24
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.061	0.21	-10000	0	-0.8	78	78
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.035	0.26	-10000	0	-0.82	88	88
STIL	-0.039	0.21	-10000	0	-0.69	82	82
DHH N/PTCH2	-0.067	0.2	-10000	0	-0.64	105	105
DHH N/PTCH1	-0.091	0.24	-10000	0	-0.75	108	108
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DHH	-0.023	0.13	-10000	0	-0.8	29	29
PTHLH	-0.084	0.38	-10000	0	-1.1	124	124
determination of left/right symmetry	-0.035	0.26	-10000	0	-0.82	88	88
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
skeletal system development	-0.081	0.38	-10000	0	-1	124	124
IHH N/Hhip	-0.014	0.046	-10000	0	-0.66	1	1
DHH N/Hhip	-0.02	0.11	-10000	0	-0.62	30	30
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.035	0.26	-10000	0	-0.82	88	88
pancreas development	-0.004	0.038	-10000	0	-0.8	1	1
HHAT	-0.001	0.025	-10000	0	-0.8	1	1
PI3K	-0.006	0.061	-10000	0	-0.61	10	10
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.044	0.18	-10000	0	-0.8	56	56
somite specification	-0.035	0.26	-10000	0	-0.82	88	88
SHH Np/Cholesterol/PTCH1	-0.072	0.21	-10000	0	-0.71	87	87
SHH Np/Cholesterol/PTCH2	-0.043	0.14	-10000	0	-0.5	83	83
SHH Np/Cholesterol/Megalin	-0.14	0.22	-10000	0	-0.5	266	266
SHH	0.01	0.036	-10000	0	-0.62	1	1
catabolic process	-0.048	0.26	-10000	0	-0.68	124	124
SMO/Vitamin D3	-0.075	0.23	-10000	0	-0.77	86	86
SHH Np/Cholesterol/Hhip	-0.005	0.034	-10000	0	-0.5	2	2
LRP2	-0.22	0.35	-10000	0	-0.8	265	265
receptor-mediated endocytosis	-0.15	0.25	-10000	0	-0.81	96	96
SHH Np/Cholesterol/BOC	-0.041	0.13	-10000	0	-0.5	79	79
SHH Np/Cholesterol/CDO	-0.01	0.06	-10000	0	-0.49	14	14
mesenchymal cell differentiation	0.005	0.034	0.5	2	-10000	0	2
mol:Vitamin D3	-0.031	0.22	-10000	0	-0.71	88	88
IHH N/PTCH2	-0.066	0.19	-10000	0	-0.69	82	82
CDON	-0.01	0.09	-10000	0	-0.8	13	13
IHH N/PTCH1	-0.045	0.26	-10000	0	-0.69	124	124
Megalin/LRPAP1	-0.16	0.27	-10000	0	-0.61	265	265
PTCH2	-0.065	0.22	-10000	0	-0.8	82	82
SHH Np/Cholesterol	-0.003	0.025	-10000	0	-0.5	1	1
PTCH1	-0.048	0.26	-10000	0	-0.68	124	124
HHIP	-0.004	0.038	-10000	0	-0.8	1	1

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.009	-9999	-0.29	1	1
CCL5	-0.014	0.077	-9999	-0.35	42	42
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.075	0.11	-9999	-0.34	98	98
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.07	0.097	-9999	-0.35	40	40
Syndecan-1/Syntenin	-0.069	0.096	-9999	-0.35	40	40
MAPK3	-0.044	0.095	-9999	-0.48	5	5
HGF/MET	-0.14	0.28	-9999	-0.66	217	217
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.28	1	1
BSG	0	0.009	-9999	-0.29	1	1
keratinocyte migration	-0.069	0.095	-9999	-0.35	40	40
Syndecan-1/RANTES	-0.077	0.11	-9999	-0.4	43	43
Syndecan-1/CD147	-0.061	0.094	-9999	-0.52	5	5
Syndecan-1/Syntenin/PIP2	-0.067	0.093	-9999	-0.34	40	40
LAMA5	0	0.009	-9999	-0.29	1	1
positive regulation of cell-cell adhesion	-0.066	0.091	-9999	-0.33	40	40
MMP7	-0.12	0.28	-9999	-0.71	175	175
HGF	-0.053	0.2	-9999	-0.8	67	67
Syndecan-1/CASK	-0.071	0.1	-9999	-0.33	98	98
Syndecan-1/HGF/MET	-0.16	0.25	-9999	-0.59	219	219
regulation of cell adhesion	-0.035	0.093	-9999	-0.49	4	4
HPSE	-0.007	0.052	-9999	-0.34	20	20
positive regulation of cell migration	-0.075	0.11	-9999	-0.34	98	98
SDC1	-0.076	0.11	-9999	-0.34	98	98
Syndecan-1/Collagen	-0.075	0.11	-9999	-0.34	98	98
PPIB	-0.001	0.015	-9999	-0.29	3	3
MET	-0.13	0.3	-9999	-0.8	171	171
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.29	437	437
MAPK1	-0.044	0.095	-9999	-0.48	5	5
homophilic cell adhesion	-0.075	0.11	-9999	-0.34	98	98
MMP1	-0.22	0.12	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.051	0.2	-9999	-0.82	66	66
PDGF/PDGFRA/CRKL	-0.04	0.15	-9999	-0.62	65	65
positive regulation of JUN kinase activity	-0.03	0.12	-9999	-0.47	65	65
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.043	0.15	-9999	-0.62	65	65
AP1	-0.37	0.54	-9999	-1.2	307	307
mol:IP3	-0.034	0.16	-9999	-0.64	65	65
PLCG1	-0.034	0.16	-9999	-0.64	65	65
PDGF/PDGFRA/alphaV Integrin	-0.04	0.15	-9999	-0.62	65	65
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.034	0.16	-9999	-0.64	65	65
CAV3	-0.001	0.015	-9999	-0.29	3	3
CAV1	-0.17	0.33	-9999	-0.8	217	217
SHC/Grb2/SOS1	-0.031	0.12	-9999	-0.48	65	65
PDGF/PDGFRA/Shf	-0.04	0.15	-9999	-0.62	65	65
FOS	-0.33	0.55	-9999	-1.1	307	307
JUN	-0.025	0.068	-9999	-0.69	9	9
oligodendrocyte development	-0.039	0.15	-9999	-0.62	65	65
GRB2	0	0.009	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:DAG	-0.034	0.16	-9999	-0.64	65	65
PDGF/PDGFRA	-0.051	0.2	-9999	-0.82	66	66
actin cytoskeleton reorganization	-0.04	0.15	-9999	-0.62	66	66
SRF	0.015	0.022	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.039	0.14	-9999	-0.54	74	74
PDGF/PDGFRA/Crk/C3G	-0.034	0.13	-9999	-0.53	65	65
JAK1	-0.024	0.16	-9999	-0.62	66	66
ELK1/SRF	-0.027	0.12	-9999	-0.48	65	65
SHB	-0.001	0.027	-9999	-0.54	2	2
SHF	-0.001	0.027	-9999	-0.54	2	2
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.036	0.17	-9999	-0.66	65	65
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.03	0.12	-9999	-0.47	65	65
PDGF/PDGFRA/SHB	-0.04	0.15	-9999	-0.62	66	66
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.72	239	239
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.034	0.16	-9999	-0.59	65	65
PIK3CA	0	0.009	-9999	-0.29	1	1
PDGF/PDGFRA/Crk	-0.04	0.15	-9999	-0.62	65	65
JAK-STAT cascade	-0.024	0.16	-9999	-0.61	66	66
cell proliferation	-0.04	0.15	-9999	-0.62	65	65

×

TCGA08_rtk_signaling

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
PDGFRA	-0.051	0.2	-10000	0	-0.79	66	66
HRAS	-0.002	0.025	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	384	384
AKT	0.014	0.077	-10000	0	-0.56	16	16
FOXO3	-0.002	0.043	-10000	0	-0.8	3	3
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.008	0.079	-10000	0	-0.8	10	10
AKT3	-0.013	0.1	-10000	0	-0.8	16	16
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.13	0.3	-10000	0	-0.8	171	171
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
PIK3CG	-0.013	0.098	-10000	0	-0.69	19	19
PIK3R3	0	0.009	-10000	0	-10000	0	0
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.025	-10000	0	-0.8	1	1
RAS	-0.095	0.16	0.26	1	-0.26	422	423
ERBB2	-0.022	0.077	-10000	0	-0.29	80	80
proliferation/survival/translation	-0.005	0.057	0.25	13	-10000	0	13
PI3K	-0.085	0.16	-10000	0	-0.26	394	394
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
FOXO	0.026	0.029	-10000	0	-0.5	1	1
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.8	2	2

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	-0.002	0.036	-9999	-0.8	2	2
LAT2	-0.062	0.14	-9999	-0.43	84	84
AP1	-0.16	0.22	-9999	-0.44	326	326
mol:PIP3	-0.027	0.2	-9999	-0.5	87	87
IKBKB	0.002	0.12	-9999	-0.32	47	47
AKT1	-0.082	0.17	-9999	-0.68	39	39
IKBKG	0.002	0.12	-9999	-0.32	47	47
MS4A2	-0.066	0.22	-9999	-0.78	87	87
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
MAP3K1	0.006	0.13	-9999	-0.44	37	37
mol:Ca2+	-0.013	0.15	-9999	-0.37	87	87
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.061	0.14	-9999	-0.42	84	84
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.065	0.16	-9999	-0.49	134	134
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.097	0.21	-9999	-0.49	201	201
PTPN13	-0.031	0.17	-9999	-0.54	62	62
PTPN11	0.01	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.006	0.15	-9999	-0.42	38	38
SYK	0.011	0.01	-9999	-10000	0	0
GRB2	0	0.009	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.086	0.18	-9999	-0.52	87	87
LAT	-0.063	0.14	-9999	-0.43	85	85
PAK2	-0.003	0.14	-9999	-0.5	38	38
NFATC2	-0.1	0.24	-9999	-0.81	93	93
HRAS	-0.012	0.15	-9999	-0.54	39	39
GAB2	-0.004	0.044	-9999	-0.38	11	11
PLA2G1B	0.028	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.25	-9999	-0.6	201	201
Antigen/IgE/Fc epsilon R1	-0.11	0.23	-9999	-0.56	201	201
mol:GDP	-0.019	0.15	-9999	-0.55	40	40
JUN	-0.007	0.075	-9999	-0.8	9	9
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
FOS	-0.24	0.37	-9999	-0.8	307	307
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.066	0.14	-9999	-0.45	87	87
CHUK	0.002	0.12	-9999	-0.32	47	47
KLRG1	-0.061	0.13	-9999	-0.5	46	46
VAV1	-0.063	0.14	-9999	-0.44	87	87
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.061	0.14	-9999	-0.42	84	84
negative regulation of mast cell degranulation	-0.056	0.12	-9999	-0.5	37	37
BTK	-0.06	0.14	-9999	-0.52	45	45
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.085	0.2	-9999	-0.42	203	203
GAB2/PI3K/SHP2	-0.091	0.19	-9999	-0.75	41	41
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.069	0.16	-9999	-0.37	159	159
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.51	203	203
FCER1G	0.003	0.012	-9999	-0.28	1	1
FCER1A	-0.11	0.29	-9999	-0.81	151	151
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.22	-9999	-0.52	201	201
MAPK3	0.026	0.018	-9999	-10000	0	0
MAPK1	0.026	0.018	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.01	0.077	-9999	-0.68	8	8
DUSP1	-0.1	0.27	-9999	-0.8	134	134
NF-kappa-B/RelA	-0.027	0.054	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.026	0.15	-9999	-0.55	37	37
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.057	0.13	-9999	-0.53	43	43
FER	-0.066	0.15	-9999	-0.45	92	92
RELA	0	0	-9999	-10000	0	0
ITK	-0.036	0.12	-9999	-0.6	39	39
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.016	0.16	-9999	-0.57	40	40
cytokine secretion	-0.019	0.04	-9999	-10000	0	0
SPHK1	-0.064	0.14	-9999	-0.44	87	87
PTK2	-0.028	0.16	-9999	-0.57	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.089	0.19	-9999	-0.45	201	201
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.022	0.2	-9999	-0.49	88	88
MAP2K2	0.022	0.019	-9999	-10000	0	0
MAP2K1	0.022	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.12	-9999	-0.51	37	37
MAP2K4	0.016	0.034	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.11	0.23	-9999	-0.55	203	203
mol:Choline	-0.095	0.2	-9999	-0.48	201	201
SHC/Grb2/SOS1	-0.055	0.12	-9999	-0.53	35	35
FYN	-0.002	0.036	-9999	-0.8	2	2
DOK1	-0.001	0.018	-9999	-10000	0	0
PXN	-0.018	0.14	-9999	-0.53	35	35
HCLS1	-0.061	0.14	-9999	-0.42	84	84
PRKCB	-0.015	0.16	-9999	-0.38	92	92
FCGR2B	-0.003	0.051	-9999	-0.7	5	5
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.057	0.12	-9999	-0.52	37	37
LCP2	0	0.009	-9999	-0.29	1	1
PLA2G4A	-0.11	0.21	-9999	-0.5	183	183
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.095	0.2	-9999	-0.48	201	201
IKK complex	0.019	0.093	-9999	-0.23	43	43
WIPF1	0	0	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.043	-9999	-0.63	4	4
PDGFRB	0.004	0.051	-9999	-0.81	4	4
SPHK1	-0.025	0.056	-9999	-1.1	2	2
mol:S1P	-0.031	0.059	-9999	-0.97	2	2
S1P1/S1P/Gi	-0.099	0.23	-9999	-0.56	95	95
GNAO1	-0.024	0.14	-9999	-0.49	66	66
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.6	64	64
PLCG1	-0.089	0.22	-9999	-0.56	83	83
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.051	-9999	-0.81	4	4
GNAI2	0.008	0.006	-9999	-10000	0	0
GNAI3	0.008	0.006	-9999	-10000	0	0
GNAI1	-0.032	0.18	-9999	-0.82	49	49
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.041	-9999	-0.55	4	4
S1P1/S1P	-0.044	0.074	-9999	-0.64	6	6
negative regulation of cAMP metabolic process	-0.096	0.22	-9999	-0.37	356	356
MAPK3	-0.16	0.31	-9999	-0.57	346	346
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.003	0.051	-9999	-0.81	4	4
PLCB2	-0.008	0.085	-9999	-0.54	7	7
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.06	-9999	-0.52	6	6
receptor internalization	-0.042	0.069	-9999	-0.58	6	6
PTGS2	-0.33	0.55	-9999	-1.1	345	345
Rac1/GTP	-0.037	0.06	-9999	-0.52	6	6
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.03	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.096	0.22	-9999	-0.37	356	356
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0	0.077	-9999	-0.81	9	9
MAPK1	-0.16	0.31	-9999	-0.57	346	346
S1P1/S1P/PDGFB-D/PDGFRB	-0.02	0.11	-9999	-0.69	8	8
ABCC1	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.009	0.05	-10000	0	-0.43	10	10
adherens junction organization	0.03	0.068	-10000	0	-0.44	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.18	-10000	0	-0.38	386	386
FMN1	0.022	0.094	-10000	0	-0.46	22	22
mol:IP3	-0.009	0.048	-10000	0	-0.4	10	10
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.057	-10000	0	-0.32	33	33
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.01	0.05	-10000	0	-0.39	10	10
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.089	-10000	0	-0.51	32	32
CTNND1	0.011	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.032	0.06	-10000	0	-10000	0	0
VASP	0.032	0.061	-10000	0	-10000	0	0
ZYX	0.032	0.061	-10000	0	-10000	0	0
JUB	0.03	0.068	-10000	0	-0.42	4	4
EGFR(dimer)	-0.17	0.21	-10000	0	-0.44	380	380
E-cadherin/beta catenin-gamma catenin	-0.016	0.091	-10000	0	-0.51	33	33
mol:PI-3-4-5-P3	-0.011	0.054	-10000	0	-0.41	10	10
PIK3CA	0	0.009	-10000	0	-0.28	1	1
PI3K	-0.011	0.055	-10000	0	-0.42	10	10
FYN	0.04	0.054	-10000	0	-0.38	2	2
mol:Ca2+	-0.009	0.047	-10000	0	-0.39	10	10
JUP	0	0.027	-10000	0	-0.54	2	2
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:DAG	-0.009	0.048	-10000	0	-0.4	10	10
CDH1	-0.025	0.14	-10000	0	-0.8	32	32
RhoA/GDP	-0.14	0.18	-10000	0	-0.38	386	386
establishment of polarity of embryonic epithelium	0.032	0.06	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	384	384
CASR	0.008	0.054	-10000	0	-0.37	10	10
RhoA/GTP	-0.008	0.043	-10000	0	-0.35	10	10
AKT2	-0.01	0.05	-10000	0	-0.39	10	10
actin cable formation	0.029	0.092	-10000	0	-0.44	22	22
apoptosis	0.01	0.051	0.4	10	-10000	0	10
CTNNA1	0.011	0.002	-10000	0	-10000	0	0
mol:GDP	-0.16	0.2	-10000	0	-0.41	386	386
PIP5K1A	0.032	0.061	-10000	0	-10000	0	0
PLCG1	-0.009	0.049	-10000	0	-0.41	10	10
Rac1/GTP	-0.15	0.2	-10000	0	-0.4	380	380
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.057	0.11	-9999	-0.29	202	202
mol:Halofuginone	0	0.003	-9999	-10000	0	0
ITGA1	-0.008	0.079	-9999	-0.8	10	10
CDKN1A	-0.058	0.09	-9999	-0.85	2	2
PRL-3/alpha Tubulin	-0.002	0.017	-9999	-10000	0	0
mol:Ca2+	-0.034	0.097	-9999	-0.63	14	14
AGT	-0.049	0.13	-9999	-0.33	149	149
CCNA2	-0.16	0.24	-9999	-0.5	325	325
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.18	0.3	-9999	-0.61	325	325
CDK2/Cyclin E1	-0.067	0.091	-9999	-0.82	2	2
MAPK3	0.021	0.019	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.006	-9999	-10000	0	0
MAPK1	0.021	0.019	-9999	-10000	0	0
PTP4A1	-0.12	0.24	-9999	-0.47	325	325
PTP4A3	-0.003	0.027	-9999	-0.29	9	9
PTP4A2	0	0.009	-9999	-0.29	1	1
ITGB1	0.021	0.019	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
RAC1	-0.057	0.083	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.14	0.2	-9999	-0.43	325	325
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.008	-9999	-10000	0	0
RHOC	-0.057	0.083	-9999	-10000	0	0
RHOA	-0.057	0.083	-9999	-0.22	1	1
cell motility	-0.036	0.1	-9999	-0.24	1	1
PRL-1/alpha Tubulin	-0.14	0.2	-9999	-0.63	1	1
PRL-3/alpha1 Integrin	-0.008	0.063	-9999	-0.61	10	10
ROCK1	-0.036	0.11	-9999	-0.24	1	1
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.12	0.24	-9999	-0.47	325	325
ATF5	-0.001	0.018	-9999	-0.29	4	4

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.008	0.057	-9999	-0.46	15	15
RGS9BP	-0.017	0.068	-9999	-0.29	61	61
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.028	-9999	-0.29	10	10
mol:Na +	-0.02	0.051	-9999	-10000	0	0
mol:ADP	0.008	0.026	-9999	-10000	0	0
GNAT2	-0.001	0.018	-9999	-0.29	4	4
RGS9-1/Gbeta5/R9AP	-0.064	0.16	-9999	-0.54	104	104
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.014	-9999	-10000	0	0
GRK7	-0.002	0.024	-9999	-0.29	7	7
CNGB3	-0.011	0.054	-9999	-0.29	38	38
Cone Metarhodopsin II/X-Arrestin	-0.002	0.017	-9999	-10000	0	0
mol:Ca2+	-0.095	0.079	-9999	-10000	0	0
Cone PDE6	-0.056	0.14	-9999	-0.47	104	104
Cone Metarhodopsin II	-0.002	0.017	-9999	-10000	0	0
Na + (4 Units)	-0.096	0.079	-9999	-10000	0	0
GNAT2/GDP	-0.055	0.14	-9999	-0.46	104	104
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.005	0.015	-9999	-10000	0	0
Cone Transducin	-0.008	0.06	-9999	-0.49	15	15
SLC24A2	-0.17	0.14	-9999	-0.29	616	616
GNB3/GNGT2	-0.01	0.074	-9999	-0.61	15	15
GNB3	-0.011	0.091	-9999	-0.7	16	16
GNAT2/GTP	-0.001	0.012	-9999	-10000	0	0
CNGA3	-0.026	0.083	-9999	-0.29	94	94
ARR3	-0.002	0.025	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.02	0.051	-9999	-10000	0	0
mol:Pi	-0.064	0.16	-9999	-0.54	104	104
Cone CNG Channel	-0.015	0.039	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.17	0.14	-9999	-0.28	616	616
RGS9	-0.086	0.24	-9999	-0.74	118	118
PDE6C	0	0.009	-9999	-0.29	1	1
GNGT2	-0.002	0.036	-9999	-0.8	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.02	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.05	-9999	-0.8	4	4
alphaV beta3 Integrin	-0.022	0.11	-9999	-0.61	35	35
PTK2	-0.066	0.19	-9999	-0.57	111	111
positive regulation of JNK cascade	-0.038	0.11	-9999	-0.34	111	111
CDC42/GDP	-0.001	0.16	-9999	-0.46	111	111
Rac1/GDP	0.001	0.16	-9999	-0.46	111	111
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.047	0.13	-9999	-0.42	111	111
nectin-3/I-afadin	-0.069	0.2	-9999	-0.64	111	111
RAPGEF1	-0.009	0.18	-9999	-0.53	111	111
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.023	0.21	-9999	-0.61	111	111
PDGFB-D/PDGFRB	-0.003	0.05	-9999	-0.8	4	4
TLN1	0.001	0.1	-9999	-0.55	13	13
Rap1/GTP	-0.04	0.11	-9999	-0.36	111	111
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.038	-9999	-0.49	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.64	111	111
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.012	0.2	-9999	-0.58	111	111
MLLT4	-0.005	0.062	-9999	-0.73	7	7
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.057	0.17	-9999	-0.5	116	116
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.047	-9999	-0.61	6	6
positive regulation of lamellipodium assembly	-0.039	0.11	-9999	-0.36	111	111
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.087	0.25	-9999	-0.8	110	110
PVRL2	-0.001	0.013	-9999	-0.29	2	2
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
CDH1	-0.025	0.14	-9999	-0.8	32	32
CLDN1	-0.036	0.15	-9999	-0.58	64	64
JAM-A/CLDN1	-0.074	0.19	-9999	-0.53	138	138
SRC	-0.077	0.22	-9999	-0.7	111	111
ITGB3	-0.029	0.15	-9999	-0.75	39	39
nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.047	-9999	-0.61	6	6
FARP2	-0.017	0.2	-9999	-0.57	111	111
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.06	0.18	-9999	-0.55	111	111
nectin-1/I-afadin	-0.004	0.047	-9999	-0.61	6	6
nectin-2/I-afadin	-0.004	0.048	-9999	-0.61	6	6
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.06	0.18	-9999	-0.55	111	111
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.038	0.11	-9999	-0.34	111	111
alphaV/beta3 Integrin/Talin	-0.041	0.13	-9999	-0.59	40	40
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-9999	-0.61	6	6
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.048	-9999	-0.61	6	6
PIP5K1C	-0.033	0.1	-9999	-0.29	115	115
VAV2	-0.019	0.2	-9999	-0.58	111	111
RAP1/GDP	-0.047	0.13	-9999	-0.42	111	111
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.06	0.18	-9999	-0.55	111	111
nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.64	111	111
Rac1/GTP	-0.048	0.14	-9999	-0.44	111	111
PTPRM	-0.037	0.11	-9999	-0.33	115	115
E-cadherin/beta catenin/alpha catenin	-0.016	0.083	-9999	-0.44	37	37
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.004	0.047	-10000	0	-0.52	8	8
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.004	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.069	0.22	-10000	0	-0.8	88	88
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
TLE1	-0.006	0.071	-10000	0	-0.8	8	8
AP1	-0.11	0.18	-10000	0	-0.37	311	311
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.001	0.036	-10000	0	-0.8	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.044	-10000	0	-10000	0	0
NICD/RBPSUH	-0.001	0.031	-10000	0	-0.71	2	2
WIF1	-0.42	0.4	-10000	0	-0.79	544	544
NOTCH1	-0.002	0.033	-10000	0	-0.75	2	2
PSENEN	0	0.009	-10000	0	-0.29	1	1
KREMEN2	-0.14	0.14	-10000	0	-0.29	486	486
DKK1	-0.079	0.19	-10000	0	-0.42	190	190
beta catenin/beta TrCP1	-0.009	0.024	0.22	4	-10000	0	4
APH1B	-0.001	0.025	-10000	0	-0.8	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.012	-10000	0	-0.21	2	2
CtBP/CBP/TCF1/TLE1/AES	0.003	0.04	-10000	0	-0.35	6	6
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.37	-10000	0	-0.8	307	307
JUN	-0.007	0.075	-10000	0	-0.8	9	9
MAP3K7	0.001	0.01	-10000	0	-0.29	1	1
CTNNB1	-0.003	0.035	0.23	4	-10000	0	4
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.081	0.11	-10000	0	-0.61	28	28
HNF1A	-0.001	0.024	-10000	0	-0.29	7	7
CTBP1	0.001	0.004	-10000	0	-10000	0	0
MYC	-0.034	0.22	-10000	0	-1.5	23	23
NKD1	-0.009	0.071	-10000	0	-0.43	22	22
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.04	0.13	-10000	0	-0.45	90	90
apoptosis	-0.11	0.18	-10000	0	-0.37	311	311
Delta 1/NOTCHprecursor	-0.004	0.046	-10000	0	-0.51	8	8
DLL1	-0.005	0.061	-10000	0	-0.8	6	6
PPARD	-0.001	0.012	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.014	-10000	0	-0.45	1	1
APC	0.003	0.012	-10000	0	-10000	0	0
DVL1	-0.038	0.036	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.14	-10000	0	-0.58	51	51
LRP6	0	0.009	-10000	0	-10000	0	0
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.01	0.085	-10000	0	-1.5	3	3
WNT1	-0.001	0.013	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.011	0.036	-10000	0	-10000	0	0
DKK2	-0.023	0.13	-10000	0	-0.77	30	30
NOTCH1 precursor/DVL1	-0.018	0.032	-10000	0	-0.63	2	2
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	0.001	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.04	0.13	-10000	0	-0.45	90	90
PPP2R5D	-0.015	0.038	0.36	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.25	0.24	-10000	0	-0.48	531	531
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.011	0.058	-10000	0	-0.33	33	33
epithelial cell differentiation	-0.014	0.079	-10000	0	-0.45	32	32
CYFIP2	-0.011	0.068	-10000	0	-0.35	32	32
ENAH	0.056	0.063	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	384	384
EPHA2	-0.005	0.061	-10000	0	-0.8	6	6
MYO6	-0.014	0.076	-10000	0	-0.43	33	33
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.006	0.04	-10000	0	-0.53	4	4
AQP5	-0.24	0.3	-10000	0	-0.6	405	405
CTNND1	0	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.073	-10000	0	-0.42	32	32
regulation of calcium-dependent cell-cell adhesion	-0.036	0.12	-10000	0	-0.43	84	84
EGF	-0.17	0.33	-10000	0	-0.8	214	214
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.039	0.14	-10000	0	-0.57	54	54
cortical microtubule organization	-0.014	0.079	-10000	0	-0.45	32	32
GO:0000145	0.024	0.076	-10000	0	-0.4	32	32
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.014	0.079	-10000	0	-0.46	32	32
MLLT4	-0.005	0.062	-10000	0	-0.73	7	7
ARF6/GDP	-0.013	0.066	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.038	-10000	0	-0.48	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.034	0.08	-10000	0	-0.39	32	32
PVRL2	-0.001	0.013	-10000	0	-0.29	2	2
ZYX	-0.013	0.074	-10000	0	-0.43	32	32
ARF6/GTP	-0.003	0.034	-10000	0	-0.44	6	6
CDH1	-0.025	0.14	-10000	0	-0.8	32	32
EGFR/EGFR/EGF/EGF	-0.25	0.27	-10000	0	-0.48	538	538
RhoA/GDP	-0.013	0.073	-10000	0	-0.42	32	32
actin cytoskeleton organization	0.03	0.079	-10000	0	-0.4	33	33
IGF-1R heterotetramer	-0.021	0.12	-10000	0	-0.61	35	35
GIT1	-0.001	0.02	-10000	0	-0.29	5	5
IGF1R	-0.021	0.12	-10000	0	-0.61	35	35
IGF1	-0.18	0.33	-10000	0	-0.8	225	225
DIAPH1	-0.002	0.045	-10000	0	-0.7	4	4
Wnt receptor signaling pathway	0.014	0.079	0.45	32	-10000	0	32
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.013	0.067	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	0.03	0.081	-10000	0	-0.41	33	33
EFNA1	0	0	-10000	0	-10000	0	0
LPP	0.029	0.086	-10000	0	-0.4	39	39
Ephrin A1/EPHA2	-0.015	0.077	-10000	0	-0.41	38	38
SEC6/SEC8	-0.014	0.073	-10000	0	-0.76	1	1
MGAT3	-0.036	0.12	-10000	0	-0.44	84	84
HGF/MET	-0.11	0.21	-10000	0	-0.46	241	241
HGF	-0.053	0.2	-10000	0	-0.8	67	67
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.011	0.058	-10000	0	-0.33	33	33
actin cable formation	0.07	0.061	-10000	0	-0.33	1	1
KIAA1543	0.03	0.09	-10000	0	-0.44	33	33
KIFC3	-0.014	0.077	-10000	0	-0.43	34	34
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.014	0.076	-10000	0	-0.43	33	33
NCK1/GIT1	-0.001	0.013	-10000	0	-10000	0	0
mol:GDP	-0.014	0.079	-10000	0	-0.45	32	32
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.013	0.074	-10000	0	-0.43	32	32
PIP5K1C	-0.013	0.074	-10000	0	-0.43	32	32
LIMA1	-0.001	0.025	-10000	0	-0.8	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.012	0.059	-10000	0	-10000	0	0
adherens junction assembly	0.046	0.086	-10000	0	-0.64	4	4
IGF-1R heterotetramer/IGF1	-0.11	0.2	-10000	0	-0.44	261	261
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-10000	0	-0.61	6	6
MET	-0.13	0.3	-10000	0	-0.8	171	171
PLEKHA7	-0.014	0.081	-10000	0	-0.45	32	32
mol:GTP	-0.003	0.037	-10000	0	-0.48	6	6
establishment of epithelial cell apical/basal polarity	-0.013	0.069	-10000	0	-0.72	1	1
cortical actin cytoskeleton stabilization	-0.011	0.058	-10000	0	-0.33	33	33
regulation of cell-cell adhesion	0.03	0.079	-10000	0	-0.4	33	33
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.011	0.058	-10000	0	-0.33	33	33

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.12	0.21	-10000	0	-0.48	247	247
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.02	-10000	0	-10000	0	0
GNB1/GNG2	-0.006	0.058	-10000	0	-0.54	12	12
GNB1	0	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.22	-10000	0	-0.5	244	244
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.027	0.049	0.11	244	-10000	0	244
GNAL	-0.19	0.34	-10000	0	-0.8	244	244
GNG2	-0.009	0.087	-10000	0	-0.8	12	12
CRH	-0.003	0.03	-10000	0	-0.29	11	11
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.038	-10000	0	-0.45	7	7
MAPK11	0.007	0.025	-10000	0	-0.45	3	3

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.025	-10000	0	-0.8	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.011	0.075	0.61	1	-10000	0	1
CDKN1A	-0.002	0.042	-10000	0	-0.95	2	2
KAT2B	-0.001	0.025	-10000	0	-0.8	1	1
BAX	-0.001	0.02	-10000	0	-0.29	5	5
FOXO3	-0.001	0.018	-10000	0	-0.33	3	3
FOXO1	-0.008	0.079	-10000	0	-0.8	10	10
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.57	0.36	-10000	0	-0.78	739	739
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.03	-10000	0	-0.61	1	1
PPARGC1A	-0.18	0.33	-10000	0	-0.8	219	219
FHL2	-0.005	0.061	-10000	0	-0.8	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.011	0.075	-10000	0	-0.62	1	1
SIRT1/FOXO3a	0	0.015	-10000	0	-0.25	3	3
SIRT1	0	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.018	-10000	0	-0.53	1	1
SIRT1/Histone H1b	-0.003	0.011	-10000	0	-10000	0	0
apoptosis	0	0.012	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.12	0.22	-10000	0	-0.54	219	219
p53/SIRT1	0.001	0.019	0.43	2	-10000	0	2
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.061	-10000	0	-0.49	16	16
HIST1H1E	-0.005	0.014	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.024	0.53	1	-10000	0	1
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.012	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.43	0.28	-10000	0	-0.61	712	712
ACSS2	0.019	0.021	-10000	0	-0.62	1	1
SIRT1/PCAF/MYOD	-0.002	0.024	-10000	0	-0.53	1	1

×

FAS signaling pathway (CD95)

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
SPTAN1	0.011	0.053	0.29	36	-10000	0	36
RFC1	0.011	0.053	0.29	36	-10000	0	36
PRKDC	0.01	0.054	0.29	36	-10000	0	36
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.023	0.037	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.015	0.066	0.25	17	-0.38	14	31
MAP2K4	-0.058	0.16	-10000	0	-0.52	17	17
mol:ceramide	-0.03	0.11	-10000	0	-0.57	17	17
GSN	0.004	0.078	0.29	35	-0.5	13	48
FASLG/FAS/FADD/FAF1/Caspase 8	-0.029	0.071	0.23	13	-0.46	14	27
FAS	0.004	0.052	-10000	0	-0.81	4	4
BID	0.001	0.011	0.32	1	-10000	0	1
MAP3K1	-0.021	0.093	-10000	0	-0.3	9	9
MAP3K7	0	0.009	-10000	0	-0.28	1	1
RB1	0.01	0.053	0.29	35	-0.3	1	36
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.27	-10000	0	-0.6	233	233
ARHGDIB	0.01	0.054	0.29	36	-10000	0	36
FADD	0.003	0.038	-10000	0	-0.3	15	15
actin filament polymerization	-0.004	0.078	0.5	13	-0.29	35	48
NFKB1	-0.076	0.1	-10000	0	-10000	0	0
MAPK8	-0.12	0.24	-10000	0	-0.43	375	375
DFFA	0.011	0.053	0.29	36	-10000	0	36
DNA fragmentation during apoptosis	0.011	0.053	0.29	36	-10000	0	36
FAS/FADD/MET	-0.094	0.21	-10000	0	-0.56	171	171
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.053	-10000	0	-0.3	27	27
FAF1	0.008	0.006	-10000	0	-10000	0	0
PARP1	0.011	0.053	0.29	36	-10000	0	36
DFFB	0.011	0.053	0.29	36	-10000	0	36
CHUK	-0.066	0.088	-10000	0	-10000	0	0
FASLG	-0.014	0.1	-10000	0	-0.41	52	52
FAS/FADD	-0.005	0.048	-10000	0	-0.67	4	4
HGF	-0.053	0.2	-10000	0	-0.8	67	67
LMNA	0.01	0.048	0.26	36	-10000	0	36
CASP6	0.011	0.053	0.29	36	-10000	0	36
CASP10	0.004	0.052	-10000	0	-0.81	4	4
CASP3	0.013	0.064	0.34	37	-10000	0	37
PTPN13	-0.025	0.14	-10000	0	-0.8	32	32
CASP8	0.003	0.02	0.45	1	-10000	0	1
IL6	-0.47	0.67	-10000	0	-1.4	373	373
MET	-0.13	0.3	-10000	0	-0.8	171	171
ICAD/CAD	0.01	0.049	0.26	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 10	-0.03	0.12	-10000	0	-0.58	17	17
activation of caspase activity by cytochrome c	0.001	0.011	0.32	1	-10000	0	1
PAK2	0.011	0.053	0.28	36	-10000	0	36
BCL2	-0.024	0.15	-10000	0	-0.8	36	36

×

PLK1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.028	0.028	-9999	-10000	0	0
BUB1B	-0.036	0.05	-9999	-10000	0	0
PLK1	-0.007	0.023	-9999	-10000	0	0
PLK1S1	0.001	0.013	-9999	-10000	0	0
KIF2A	0.003	0.02	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.007	0.023	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.17	0.12	-9999	-0.27	503	503
WEE1	-0.001	0.023	-9999	-10000	0	0
cytokinesis	-0.05	0.055	-9999	-0.26	10	10
PP2A-alpha B56	0.031	0.021	-9999	-10000	0	0
AURKA	0.002	0.013	-9999	-10000	0	0
PICH/PLK1	-0.073	0.093	-9999	-0.33	10	10
CENPE	-0.049	0.084	-9999	-0.21	2	2
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.003	0.02	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.004	0.015	-9999	-10000	0	0
PAK1	-0.006	0.042	-9999	-0.28	23	23
SPC24	-0.18	0.14	-9999	-0.29	632	632
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.004	0.016	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.004	0.013	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.025	-9999	-0.8	1	1
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.007	0.023	-9999	-10000	0	0
ODF2	0	0	-9999	-10000	0	0
BUB1	0.025	0.018	-9999	-10000	0	0
TPT1	0.001	0.013	-9999	-10000	0	0
CDC25C	-0.005	0.014	-9999	-10000	0	0
CDC25B	-0.003	0.039	-9999	-0.28	19	19
SGOL1	-0.028	0.028	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.021	0.041	-9999	-10000	0	0
CDC14B	-0.01	0.11	-9999	-0.63	33	33
CDC20	-0.15	0.14	-9999	-0.29	550	550
PLK1/PBIP1	-0.028	0.052	-9999	-10000	0	0
mitosis	-0.006	0.007	-9999	-0.022	2	2
FBXO5	0.001	0.022	-9999	-0.14	1	1
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.14	-9999	-0.29	631	631
metaphase plate congression	-0.002	0.015	-9999	-10000	0	0
ERCC6L	-0.062	0.087	-9999	-10000	0	0
NLP/gamma Tubulin	0	0.013	-9999	-10000	0	0
microtubule cytoskeleton organization	0.001	0.013	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.14	0.099	-9999	-0.28	260	260
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.003	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.002	0.023	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.051	-9999	-0.29	28	28
microtubule-based process	-0.11	0.066	-9999	-0.19	7	7
Golgi organization	-0.007	0.023	-9999	-10000	0	0
Cohesin/SA2	-0.009	0.018	-9999	-0.46	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-0.29	768	768
APC/C/CDC20	-0.085	0.078	-9999	-0.19	7	7
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.028	0.052	-9999	-10000	0	0
PRC1	-0.073	0.12	-9999	-0.29	261	261
ECT2	-0.003	0.038	-9999	-0.21	2	2
C13orf34	0	0.021	-9999	-10000	0	0
NUDC	-0.002	0.015	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.036	0.049	-9999	-10000	0	0
spindle assembly	-0.003	0.019	-9999	-10000	0	0
spindle stabilization	0.001	0.013	-9999	-10000	0	0
APC/C/HCDH1	-0.018	0.096	-9999	-0.54	33	33
MKLP2/PLK1	-0.11	0.066	-9999	-0.19	7	7
CCNB1	-0.057	0.11	-9999	-0.28	207	207
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	-0.007	0.085	-9999	-0.51	27	27
TUBG1	0.001	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.022	0.039	-9999	-10000	0	0
MLF1IP	-0.027	0.074	-9999	-10000	0	0
INCENP	0	0.002	-9999	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.011	0.055	-9999	-0.29	40	40
GPC2	-0.034	0.099	-9999	-0.3	116	116
GPC2/Midkine	-0.029	0.078	-9999	-0.4	17	17
neuron projection morphogenesis	-0.029	0.078	-9999	-0.4	17	17

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.55	0.37	-9999	-0.8	700	700
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.007	0.043	-9999	-10000	0	0
TCEB1	-0.001	0.013	-9999	-10000	0	0
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.007	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.016	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.048	0.11	-9999	-0.29	172	172
ARNT/IPAS	-0.42	0.28	-9999	-0.61	700	700
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0.009	-9999	-0.29	1	1
RACK1/Elongin B/Elongin C	-0.004	0.022	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.037	-9999	-0.48	2	2
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.014	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
HIF1A/JAB1	-0.001	0.005	-9999	-10000	0	0
EGLN3	-0.021	0.078	-9999	-0.8	1	1
EGLN2	-0.002	0.022	-9999	-10000	0	0
EGLN1	-0.001	0.025	-9999	-0.8	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.004	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.018	0.038	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.001	0.11	-9999	-0.54	38	38
ADCY5	-0.16	0.26	-9999	-0.54	328	328
ADCY6	0.02	0.017	-9999	-0.54	1	1
ADCY7	0.02	0.017	-9999	-0.54	1	1
ADCY1	-0.007	0.097	-9999	-0.54	26	26
ADCY2	-0.03	0.15	-9999	-0.54	80	80
ADCY3	0.02	0.018	-9999	-0.54	1	1
ADCY8	0.009	0.032	-9999	-0.54	1	1
PRKCE	0.011	0.02	-9999	-0.62	1	1
ADCY9	0.02	0.017	-9999	-0.54	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.031	0.1	-9999	-0.31	68	68

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.017	-10000	0	-10000	0	0
AES	0.004	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
SMAD4	-0.001	0.025	-10000	0	-0.8	1	1
DKK2	-0.023	0.13	-10000	0	-0.77	30	30
TLE1	-0.003	0.073	-10000	0	-0.8	8	8
MACF1	0	0.002	-10000	0	-10000	0	0
CTNNB1	0.1	0.087	-10000	0	-10000	0	0
WIF1	-0.42	0.4	-10000	0	-0.79	544	544
beta catenin/RanBP3	0.014	0.077	0.38	38	-10000	0	38
KREMEN2	-0.14	0.14	-10000	0	-0.29	486	486
DKK1	-0.079	0.19	-10000	0	-0.42	190	190
beta catenin/beta TrCP1	0.1	0.084	-10000	0	-10000	0	0
FZD1	0	0.001	-10000	0	-10000	0	0
AXIN2	-0.013	0.21	-10000	0	-1.5	18	18
AXIN1	0.007	0.006	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.007	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.078	-10000	0	-0.52	5	5
Axin1/APC/GSK3	0.001	0.014	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.078	0.033	-10000	0	-10000	0	0
HNF1A	0.002	0.028	-10000	0	-0.29	6	6
CTBP1	0.004	0.015	-10000	0	-10000	0	0
MYC	-0.019	0.24	-10000	0	-1.6	23	23
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.081	0.11	-10000	0	-0.61	28	28
NKD1	-0.009	0.071	-10000	0	-0.43	22	22
TCF4	-0.004	0.08	-10000	0	-0.8	10	10
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.006	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.013	0.096	0.44	42	-0.43	1	43
LEF1	-0.036	0.1	-10000	0	-0.3	125	125
DVL1	0.072	0.065	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.099	0.09	-10000	0	-0.63	4	4
DKK1/LRP6/Kremen 2	-0.11	0.14	-10000	0	-0.58	51	51
LRP6	0	0.009	-10000	0	-10000	0	0
CSNK1A1	0.004	0.017	-10000	0	-10000	0	0
NLK	0.01	0.014	-10000	0	-0.29	2	2
CCND1	0.003	0.099	-10000	0	-1.6	3	3
WNT1	0	0.013	-10000	0	-10000	0	0
GSK3A	0.006	0.006	-10000	0	-10000	0	0
GSK3B	0	0.001	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.044	0.045	0.27	13	-10000	0	13
APC	0	0.007	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.14	0.13	0.27	531	-10000	0	531
CREBBP	0.004	0.015	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.033	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.021	0.034	-9999	-0.64	1	1
positive regulation of JNK cascade	-0.047	0.11	-9999	-0.43	19	19
Syndecan-4/ADAM12	-0.029	0.052	-9999	-0.55	2	2
CCL5	-0.014	0.077	-9999	-0.35	42	42
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.001	0.019	-9999	-0.28	4	4
ADAM12	-0.02	0.078	-9999	-0.3	66	66
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.02	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.053	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.071	0.14	-9999	-0.46	60	60
Syndecan-4/CXCL12/CXCR4	-0.049	0.11	-9999	-0.48	7	7
Syndecan-4/Laminin alpha3	-0.13	0.2	-9999	-0.5	114	114
MDK	-0.011	0.055	-9999	-0.29	40	40
Syndecan-4/FZD7	-0.029	0.068	-9999	-0.47	14	14
Syndecan-4/Midkine	-0.025	0.039	-9999	-0.64	1	1
FZD7	-0.017	0.11	-9999	-0.8	21	21
Syndecan-4/FGFR1/FGF	-0.18	0.21	-9999	-0.48	151	151
THBS1	-0.003	0.05	-9999	-0.8	4	4
integrin-mediated signaling pathway	-0.031	0.073	-9999	-0.47	16	16
positive regulation of MAPKKK cascade	-0.047	0.11	-9999	-0.43	19	19
Syndecan-4/TACI	-0.032	0.066	-9999	-0.5	7	7
CXCR4	-0.007	0.045	-9999	-0.29	26	26
cell adhesion	-0.022	0.059	-9999	-0.34	26	26
Syndecan-4/Dynamin	-0.02	0.033	-9999	-0.64	1	1
Syndecan-4/TSP1	-0.022	0.042	-9999	-0.5	4	4
Syndecan-4/GIPC	-0.021	0.034	-9999	-0.64	1	1
Syndecan-4/RANTES	-0.027	0.05	-9999	-0.51	5	5
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.095	0.26	-9999	-0.79	123	123
LAMA3	-0.2	0.35	-9999	-0.8	254	254
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.003	0.13	-9999	-0.76	26	26
Syndecan-4/alpha-Actinin	-0.021	0.036	-9999	-0.54	2	2
TFPI	-0.037	0.17	-9999	-0.8	47	47
F2	0.002	0.028	-9999	-0.29	9	9
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.24	-9999	-0.6	107	107
ACTN1	-0.001	0.025	-9999	-0.8	1	1
TNC	-0.021	0.12	-9999	-0.67	32	32
Syndecan-4/CXCL12	-0.054	0.11	-9999	-0.46	36	36
FGF6	-0.002	0.036	-9999	-0.8	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.062	0.22	-9999	-0.8	79	79
TNFRSF13B	-0.026	0.11	-9999	-0.4	67	67
FGF2	-0.32	0.39	-9999	-0.8	409	409
FGFR1	-0.01	0.084	-9999	-0.69	14	14
Syndecan-4/PI-4-5-P2	-0.014	0.045	-9999	-0.65	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.15	-9999	-0.29	404	404
cell migration	-0.024	0.019	-9999	-10000	0	0
PRKCD	0.004	0.014	-9999	-0.28	1	1
vasculogenesis	-0.022	0.041	-9999	-0.48	4	4
SDC4	-0.014	0.048	-9999	-0.69	1	1
Syndecan-4/Tenascin C	-0.032	0.075	-9999	-0.49	16	16
Syndecan-4/PI-4-5-P2/PKC alpha	-0.043	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.02	0.033	-9999	-0.64	1	1
MMP9	-0.12	0.15	-9999	-0.28	433	433
Rac1/GTP	-0.026	0.057	-9999	-0.35	26	26
cytoskeleton organization	-0.02	0.033	-9999	-0.61	1	1
GIPC1	-0.001	0.015	-9999	-10000	0	0
Syndecan-4/TFPI	-0.04	0.095	-9999	-0.51	10	10

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.002	0.011	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.032	0.12	0.46	25	-10000	0	25
IL27/IL27R/JAK1	-0.07	0.18	-10000	0	-0.67	38	38
TBX21	-0.042	0.21	-10000	0	-0.65	65	65
IL12B	-0.053	0.12	-10000	0	-0.29	210	210
IL12A	-0.029	0.15	-10000	0	-0.62	57	57
IL6ST	-0.087	0.26	-10000	0	-0.81	120	120
IL27RA/JAK1	-0.007	0.063	-10000	0	-1.1	3	3
IL27	-0.021	0.089	-10000	0	-0.29	65	65
TYK2	0.01	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.032	0.12	0.46	25	-10000	0	25
T cell proliferation during immune response	0.032	0.12	0.46	25	-10000	0	25
MAPKKK cascade	-0.032	0.12	-10000	0	-0.46	25	25
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.038	-10000	0	-10000	0	0
IL12RB1	-0.012	0.065	-10000	0	-0.31	40	40
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.056	0.23	-10000	0	-0.62	95	95
IL27/IL27R/JAK2/TYK2	-0.032	0.13	-10000	0	-0.47	23	23
positive regulation of T cell mediated cytotoxicity	-0.032	0.12	-10000	0	-0.46	25	25
STAT1 (dimer)	-0.09	0.22	0.5	9	-0.8	40	49
JAK2	0.004	0.026	-10000	0	-0.81	1	1
JAK1	0	0.025	-10000	0	-0.8	1	1
STAT2 (dimer)	-0.043	0.11	-10000	0	-0.48	14	14
T cell proliferation	-0.18	0.25	-10000	0	-0.48	380	380
IL12/IL12R/TYK2/JAK2	0.013	0.071	-10000	0	-10000	0	0
IL17A	-0.13	0.18	-10000	0	-10000	0	0
mast cell activation	0.032	0.12	0.46	25	-10000	0	25
IFNG	0	0.024	-10000	0	-0.079	6	6
T cell differentiation	-0.003	0.006	-10000	0	-0.019	25	25
STAT3 (dimer)	-0.043	0.11	-10000	0	-0.48	14	14
STAT5A (dimer)	-0.046	0.12	-10000	0	-0.52	18	18
STAT4 (dimer)	-0.061	0.14	-10000	0	-0.51	56	56
STAT4	-0.033	0.16	-10000	0	-0.79	42	42
T cell activation	-0.009	0.008	0.13	2	-10000	0	2
IL27R/JAK2/TYK2	-0.059	0.16	-10000	0	-0.61	24	24
GATA3	-0.035	0.27	-10000	0	-1.5	34	34
IL18	0.006	0.032	-10000	0	-0.19	26	26
positive regulation of mast cell cytokine production	-0.042	0.11	-10000	0	-0.47	14	14
IL27/EBI3	-0.025	0.083	-10000	0	-0.52	15	15
IL27RA	0	0.068	-10000	0	-1.4	2	2
IL6	-0.29	0.39	-10000	0	-0.8	373	373
STAT5A	-0.006	0.071	-10000	0	-0.8	8	8
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.027	0.48	2	-10000	0	2
IL1B	0	0.08	-10000	0	-0.62	16	16
EBI3	-0.005	0.079	-10000	0	-0.5	20	20
TNF	-0.002	0.079	-10000	0	-0.36	36	36

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.004	0.13	-10000	0	-0.4	53	53
TBX21	-0.013	0.35	-10000	0	-1.3	52	52
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.004	0.071	-10000	0	-0.32	40	40
GADD45B	0.033	0.22	-10000	0	-0.8	35	35
IL12RB2	-0.057	0.2	-10000	0	-0.44	170	170
GADD45G	0.024	0.22	-10000	0	-0.82	34	34
natural killer cell activation	0.007	0.017	-10000	0	-10000	0	0
RELB	-0.003	0.027	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.047	-10000	0	-0.28	26	26
IL2RA	-0.03	0.12	-10000	0	-0.8	14	14
IFNG	-0.04	0.099	-10000	0	-0.29	141	141
STAT3 (dimer)	0.026	0.22	-10000	0	-0.65	55	55
HLA-DRB5	-0.017	0.095	-10000	0	-0.32	78	78
FASLG	0.005	0.29	-10000	0	-1.1	41	41
NF kappa B2 p52/RelB	-0.079	0.2	-10000	0	-0.84	46	46
CD4	0.008	0.006	-10000	0	-10000	0	0
SOCS1	-0.005	0.042	-10000	0	-0.32	15	15
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.027	0.15	-10000	0	-0.5	72	72
CD3E	-0.021	0.13	-10000	0	-0.5	59	59
CD3G	-0.034	0.16	-10000	0	-0.57	75	75
IL12Rbeta2/JAK2	-0.027	0.16	-10000	0	-0.62	50	50
CCL3	0.013	0.26	-10000	0	-0.99	38	38
CCL4	0.015	0.26	-10000	0	-0.96	36	36
HLA-A	0.009	0.028	-10000	0	-0.35	1	1
IL18/IL18R	0.022	0.14	-10000	0	-0.56	51	51
NOS2	0.019	0.25	-10000	0	-0.93	40	40
IL12/IL12R/TYK2/JAK2/SPHK2	-0.003	0.13	-10000	0	-0.41	47	47
IL1R1	0.002	0.3	-10000	0	-1.2	42	42
IL4	-0.005	0.018	-10000	0	-10000	0	0
JAK2	0.016	0.03	-10000	0	-0.81	1	1
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.032	0.26	-10000	0	-1	47	47
RAB7A	0.048	0.19	-10000	0	-0.72	27	27
lysosomal transport	0.049	0.19	-10000	0	-0.66	29	29
FOS	-0.35	0.67	-10000	0	-1.3	320	320
STAT4 (dimer)	0.022	0.26	-10000	0	-0.89	50	50
STAT5A (dimer)	-0.084	0.22	-10000	0	-0.73	69	69
GZMA	0.004	0.28	-10000	0	-1.1	40	40
GZMB	-0.007	0.3	-10000	0	-1.1	45	45
HLX	-0.001	0.013	-10000	0	-10000	0	0
LCK	0.005	0.29	-10000	0	-0.83	70	70
TCR/CD3/MHC II/CD4	-0.065	0.2	-10000	0	-0.56	83	83
IL2/IL2R	-0.03	0.1	-10000	0	-0.48	39	39
MAPK14	0.037	0.22	-10000	0	-0.79	39	39
CCR5	0.027	0.22	-10000	0	-0.87	32	32
IL1B	0.003	0.11	-10000	0	-0.71	20	20
STAT6	0.026	0.086	-10000	0	-0.24	15	15
STAT4	-0.033	0.16	-10000	0	-0.79	42	42
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.038	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0.009	-10000	0	-0.29	1	1
IL12B	-0.045	0.12	-10000	0	-0.29	119	119
CD8A	-0.002	0.079	-10000	0	-0.39	33	33
CD8B	-0.024	0.15	-10000	0	-0.55	64	64
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.004	0.13	0.4	53	-10000	0	53
IL2RB	-0.012	0.064	-10000	0	-0.31	40	40
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.24	-10000	0	-0.8	50	50
IL2RG	-0.018	0.088	-10000	0	-0.36	52	52
IL12	-0.052	0.16	-10000	0	-0.61	61	61
STAT5A	-0.006	0.071	-10000	0	-0.8	8	8
CD247	-0.013	0.12	-10000	0	-0.58	38	38
IL2	-0.003	0.027	-10000	0	-0.29	9	9
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.034	0.19	-10000	0	-0.77	62	62
IL12/IL12R/TYK2/JAK2	0.008	0.29	-10000	0	-0.85	66	66
MAP2K3	0.033	0.22	-10000	0	-0.81	38	38
RIPK2	-0.001	0.02	-10000	0	-10000	0	0
MAP2K6	0.029	0.23	-10000	0	-0.78	44	44
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.028	-10000	0	-0.8	1	1
IL18RAP	-0.016	0.15	-10000	0	-0.75	40	40
IL12Rbeta1/TYK2	0.014	0.056	-10000	0	-0.65	2	2
EOMES	-0.023	0.18	-10000	0	-1.5	15	15
STAT1 (dimer)	0.03	0.22	-10000	0	-0.72	39	39
T cell proliferation	0.033	0.2	-10000	0	-0.64	49	49
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.81	17	17
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.061	0.17	-10000	0	-0.76	42	42
ATF2	0.044	0.21	-10000	0	-0.76	35	35

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.052	0.11	-9999	-0.6	4	4
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.19	0.29	-9999	-0.63	308	308
IFNAR2	0.01	0.005	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.29	151	151
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.43	277	277
NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.8	214	214
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.064	0.086	-9999	-0.6	3	3
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.15	-9999	-0.28	524	524
WRN	0	0	-9999	-10000	0	0
SP1	0.011	0.005	-9999	-10000	0	0
SP3	0.007	0.006	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.05	0.075	-9999	-0.54	3	3
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.053	0.12	-9999	-0.66	3	3
CCND1	-0.045	0.12	-9999	-1.3	3	3
MAX	0.007	0.006	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.29	8	8
RBBP4	-0.001	0.025	-9999	-0.8	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	0.007	0.021	-9999	-10000	0	0
CDKN1B	0.009	0.074	-9999	-0.88	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.29	4	4
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.003	0.005	-9999	-10000	0	0
JUN	-0.002	0.076	-9999	-0.8	9	9
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.24	0.37	-9999	-0.8	307	307
IFN-gamma/IRF1	-0.024	0.061	-9999	-0.36	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.031	0.088	-9999	-0.29	109	109
Telomerase	-0.004	0.026	-9999	-10000	0	0
IRF1	0.005	0.02	-9999	-0.28	3	3
ESR1	-0.15	0.29	-9999	-0.57	277	277
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0.011	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.022	0.006	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.007	0.011	-9999	-0.28	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.015	-9999	-0.29	3	3
TERT/NF kappa B1/14-3-3	-0.063	0.1	-9999	-0.67	3	3
NR2F2	0	0.044	-9999	-0.8	3	3
MAPK3	0.014	0.02	-9999	-10000	0	0
MAPK1	0.014	0.02	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.28	1	1
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.3	0.39	-9999	-0.8	384	384
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.35	0.36	-9999	-0.68	524	524
MYC	-0.009	0.12	-9999	-0.8	23	23
IL2	0.004	0.028	-9999	-0.28	9	9
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
TGFB1	0	0.009	-9999	-0.28	1	1
TRF2/BLM	-0.017	0.05	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.06	0.084	-9999	-0.6	3	3
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.05	0.075	-9999	-0.54	3	3
Smad3/Myc	-0.012	0.079	-9999	-0.53	23	23
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.033	0.098	-9999	-0.28	141	141
Telomerase/PinX1	-0.05	0.075	-9999	-0.54	3	3
Telomerase/AKT1/mTOR/p70S6K	0.003	0.054	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.05	0.075	-9999	-0.58	2	2
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.05	0.075	-9999	-0.54	3	3
E2F1	-0.083	0.14	-9999	-0.29	322	322
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.057	0.11	-9999	-0.29	204	204
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-0.29	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.003	0.033	-10000	0	-0.8	1	1
SVIL	-0.005	0.054	-10000	0	-0.8	4	4
ZNF318	0.024	0.06	0.22	2	-10000	0	2
JMJD2C	-0.003	0.042	-10000	0	-0.14	79	79
T-DHT/AR/Ubc9	-0.079	0.18	-10000	0	-0.55	127	127
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.002	0.012	-10000	0	-10000	0	0
PELP1	0.005	0.013	-10000	0	-10000	0	0
CTNNB1	0	0.015	-10000	0	-10000	0	0
AKT1	0.008	0.019	-10000	0	-10000	0	0
PTK2B	0	0.013	-10000	0	-10000	0	0
MED1	0.002	0.048	-10000	0	-0.28	21	21
MAK	0.013	0.11	0.27	2	-0.57	19	21
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.007	0.064	-10000	0	-0.8	6	6
GSN	-0.013	0.092	-10000	0	-0.8	13	13
NCOA2	-0.034	0.16	-10000	0	-0.8	43	43
NCOA6	-0.002	0.021	-10000	0	-10000	0	0
DNA-PK	0.023	0.06	0.22	2	-10000	0	2
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0	0.015	-10000	0	-10000	0	0
cell proliferation	-0.006	0.11	-10000	0	-0.88	11	11
XRCC5	0.007	0.016	-10000	0	-10000	0	0
UBE3A	-0.006	0.032	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.092	0.21	-10000	0	-0.59	141	141
FHL2	-0.017	0.13	-10000	0	-1.3	6	6
RANBP9	-0.001	0.019	-10000	0	-10000	0	0
JMJD1A	-0.012	0.056	-10000	0	-0.14	146	146
CDK6	-0.008	0.088	-10000	0	-0.73	14	14
TGFB1I1	-0.004	0.048	-10000	0	-0.8	3	3
T-DHT/AR/CyclinD1	-0.091	0.19	-10000	0	-0.56	130	130
XRCC6	0.007	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.065	0.21	-10000	0	-0.54	143	143
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0.016	0.04	-10000	0	-10000	0	0
BRCA1	-0.003	0.035	-10000	0	-0.49	3	3
TCF4	0.005	0.085	-10000	0	-0.8	10	10
CDKN2A	-0.039	0.11	-10000	0	-0.29	148	148
SRF	0.024	0.02	-10000	0	-10000	0	0
NKX3-1	-0.081	0.19	-10000	0	-1.3	18	18
KLK3	-0.2	0.53	-10000	0	-1.6	133	133
TMF1	0	0	-10000	0	-10000	0	0
HNRNPA1	0.009	0.022	-10000	0	-10000	0	0
AOF2	-0.009	0.024	-10000	0	-0.072	133	133
APPL1	0.035	0.034	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.07	0.19	-10000	0	-0.55	127	127
AR	-0.098	0.27	-10000	0	-0.81	128	128
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.009	0.022	-10000	0	-10000	0	0
PAWR	-0.001	0.025	-10000	0	-0.8	1	1
PRKDC	0.006	0.024	-10000	0	-0.29	3	3
PA2G4	0.012	0.029	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.066	0.17	-10000	0	-0.51	127	127
RPS6KA3	-0.009	0.074	-10000	0	-0.8	8	8
T-DHT/AR/ARA70	-0.083	0.18	-10000	0	-0.55	127	127
LATS2	0.01	0.024	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.061	0.18	-10000	0	-0.51	127	127
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.01	0.074	-10000	0	-0.69	8	8
KLK2	-0.12	0.33	-10000	0	-1.2	79	79
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.095	0.2	-10000	0	-0.54	157	157
TMPRSS2	-0.18	0.4	-10000	0	-1.2	137	137
CCND1	-0.015	0.07	-10000	0	-0.33	41	41
PIAS1	-0.006	0.032	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.034	-10000	0	-0.078	179	179
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.013	0.051	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.082	0.19	-10000	0	-0.56	138	138
CMTM2	0.004	0.013	-10000	0	-0.28	1	1
SNURF	-0.02	0.13	-10000	0	-0.8	26	26
ZMIZ1	0.003	0.031	-10000	0	-0.35	1	1
CCND3	0.002	0.011	-10000	0	-10000	0	0
TGIF1	0.009	0.022	-10000	0	-10000	0	0
FKBP4	-0.004	0.033	-10000	0	-0.37	1	1

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.004	0.02	-9999	-0.56	1	1
REL	-0.005	0.088	-9999	-0.8	12	12
HDAC7	0.009	0.13	-9999	-0.59	14	14
JUN	-0.007	0.075	-9999	-0.8	9	9
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.025	-9999	-0.8	1	1
KAT5	0.002	0.005	-9999	-10000	0	0
MAPK14	0.007	0.09	-9999	-0.62	20	20
FOXO1	-0.008	0.079	-9999	-0.8	10	10
T-DHT/AR	-0.004	0.13	-9999	-0.63	14	14
MAP2K6	-0.009	0.11	-9999	-0.78	21	21
BRM/BAF57	-0.001	0.011	-9999	-10000	0	0
MAP2K4	0.007	0.027	-9999	-0.81	1	1
SMARCA2	0	0	-9999	-10000	0	0
PDE9A	-0.09	0.29	-9999	-1.2	60	60
NCOA2	-0.034	0.16	-9999	-0.8	43	43
CEBPA	-0.005	0.075	-9999	-0.8	9	9
EHMT2	0	0.001	-9999	-10000	0	0
cell proliferation	0.014	0.14	-9999	-0.5	24	24
NR0B1	-0.01	0.053	-9999	-0.29	36	36
EGR1	-0.26	0.38	-9999	-0.8	325	325
RXRs/9cRA	-0.12	0.21	-9999	-0.49	252	252
AR/RACK1/Src	-0.004	0.11	-9999	-0.49	27	27
AR/GR	-0.052	0.13	-9999	-0.49	40	40
GNB2L1	0.001	0.004	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.29	1	1
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.015	0.058	-9999	-0.62	8	8
T-DHT/AR/TIF2/CARM1	-0.014	0.15	-9999	-0.58	39	39
SRC	0.022	0.09	-9999	-0.48	27	27
NR3C1	-0.012	0.097	-9999	-0.8	15	15
KLK3	-0.22	0.43	-9999	-1.2	156	156
APPBP2	0	0.016	-9999	-0.28	3	3
TRIM24	0.004	0.011	-9999	-0.29	1	1
T-DHT/AR/TIP60	-0.025	0.095	-9999	-0.52	27	27
TMPRSS2	-0.17	0.42	-9999	-1.2	135	135
RXRG	-0.2	0.35	-9999	-0.8	252	252
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.001	0.004	-9999	-10000	0	0
NR2C2	-0.007	0.075	-9999	-0.8	9	9
KLK2	-0.043	0.25	-9999	-0.78	88	88
AR	-0.025	0.14	-9999	-0.35	134	134
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
MDM2	0.005	0.023	-9999	-0.29	4	4
SRY	0.004	0.01	-9999	-10000	0	0
GATA2	-0.025	0.13	-9999	-0.8	27	27
MYST2	0.002	0.01	-9999	-10000	0	0
HOXB13	-0.13	0.15	-9999	-0.29	469	469
T-DHT/AR/RACK1/Src	-0.013	0.1	-9999	-0.5	27	27
positive regulation of transcription	-0.025	0.13	-9999	-0.8	27	27
DNAJA1	0.001	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.014	-9999	-10000	0	0
NCOA1	0.012	0.027	-9999	-0.83	1	1
SPDEF	-0.056	0.2	-9999	-0.63	98	98
T-DHT/AR/TIF2	0.014	0.097	-9999	-0.51	16	16
T-DHT/AR/Hsp90	-0.033	0.091	-9999	-0.52	27	27
GSK3B	0.005	0.006	-9999	-10000	0	0
NR2C1	0.002	0.006	-9999	-10000	0	0
mol:T-DHT	0.015	0.095	-9999	-0.51	27	27
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.006	0.014	-9999	-10000	0	0
POU2F1	0.021	0.026	-9999	-0.42	1	1
T-DHT/AR/DAX-1	-0.034	0.095	-9999	-0.53	27	27
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	-0.001	0.016	-9999	-0.29	3	3

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.52	59	59
MAP3K8	-0.005	0.063	-9999	-0.73	7	7
FOS	-0.035	0.14	-9999	-0.46	34	34
PRKCA	-0.013	0.13	-9999	-0.78	28	28
PTPN7	-0.008	0.07	-9999	-0.32	18	18
HRAS	-0.002	0.025	-9999	-10000	0	0
PRKCB	-0.011	0.11	-9999	-0.55	36	36
NRAS	-0.001	0.013	-9999	-0.29	2	2
RAS family/GTP	-0.002	0.014	-9999	-10000	0	0
MAPK3	-0.007	0.073	-9999	-0.29	1	1
MAP2K1	-0.012	0.14	-9999	-0.6	43	43
ELK1	-0.003	0.005	-9999	-10000	0	0
BRAF	-0.032	0.12	-9999	-0.57	43	43
mol:GTP	-0.002	0.003	-9999	-0.006	307	307
MAPK1	-0.007	0.073	-9999	-10000	0	0
RAF1	-0.032	0.12	-9999	-0.57	43	43
KRAS	-0.001	0.013	-9999	-0.28	2	2

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.035	0.12	-10000	0	-0.62	36	36
FYN	0.016	0.18	-10000	0	-0.77	40	40
LAT/GRAP2/SLP76	-0.029	0.15	-10000	0	-0.66	41	41
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	0.03	0.12	-10000	0	-0.48	39	39
B2M	0.011	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.027	-10000	0	-0.19	1	1
MAP3K8	-0.005	0.062	-10000	0	-0.73	7	7
mol:Ca2+	-0.024	0.047	-10000	0	-0.12	195	195
integrin-mediated signaling pathway	-0.002	0.029	-10000	0	-0.53	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.021	0.18	-10000	0	-0.72	42	42
TRPV6	-0.16	0.32	-10000	0	-0.78	209	209
CD28	-0.008	0.072	-10000	0	-0.8	7	7
SHC1	0.011	0.18	-10000	0	-0.8	39	39
receptor internalization	-0.002	0.2	-10000	0	-0.81	48	48
PRF1	-0.002	0.23	-10000	0	-1.1	33	33
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2	0	0.009	-10000	0	-10000	0	0
COT/AKT1	0.032	0.1	-10000	0	-0.38	41	41
LAT	0.008	0.19	-10000	0	-0.78	43	43
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.024	0.15	-10000	0	-0.49	72	72
CD3E	-0.018	0.14	-10000	0	-0.5	59	59
CD3G	-0.033	0.16	-10000	0	-0.56	75	75
RASGRP2	-0.005	0.039	-10000	0	-0.18	42	42
RASGRP1	0.036	0.12	-10000	0	-0.47	42	42
HLA-A	0.009	0.027	-10000	0	-10000	0	0
RASSF5	-0.003	0.044	-10000	0	-0.67	4	4
RAP1A/GTP/RAPL	-0.002	0.029	-10000	0	-0.54	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.043	-10000	0	-0.12	39	39
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.048	-10000	0	-0.24	27	27
PRKCA	-0.013	0.086	-10000	0	-0.32	52	52
GRAP2	-0.015	0.11	-10000	0	-0.8	18	18
mol:IP3	0.018	0.15	0.27	167	-0.46	40	207
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.008	0.22	-10000	0	-0.94	39	39
ORAI1	0.077	0.15	0.38	195	-10000	0	195
CSK	0.008	0.19	-10000	0	-0.82	39	39
B7 family/CD28	-0.025	0.18	-10000	0	-0.73	47	47
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.003	0.22	-10000	0	-0.93	43	43
PTPN6	0.007	0.19	-10000	0	-0.79	42	42
VAV1	0.009	0.19	-10000	0	-0.8	41	41
Monovalent TCR/CD3	-0.031	0.21	-10000	0	-0.71	63	63
CBL	0	0	-10000	0	-10000	0	0
LCK	0.009	0.2	-10000	0	-0.8	43	43
PAG1	0.008	0.19	-10000	0	-0.8	41	41
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.002	0.22	-10000	0	-0.91	43	43
CD80	-0.076	0.13	-10000	0	-10000	0	0
CD86	-0.001	0.02	-10000	0	-0.29	5	5
PDK1/CARD11/BCL10/MALT1	-0.018	0.058	-10000	0	-0.28	31	31
HRAS	-0.002	0.025	-10000	0	-10000	0	0
GO:0035030	-0.038	0.14	-10000	0	-0.58	47	47
CD8A	-0.001	0.079	-10000	0	-0.38	33	33
CD8B	-0.023	0.15	-10000	0	-0.55	64	64
PTPRC	-0.009	0.074	-10000	0	-0.47	20	20
PDK1/PKC theta	0.033	0.16	-10000	0	-0.6	43	43
CSK/PAG1	0.013	0.18	-10000	0	-0.81	37	37
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.016	-10000	0	-10000	0	0
GRAP2/SLP76	-0.036	0.17	-10000	0	-0.76	44	44
STIM1	0.041	0.078	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.054	-10000	0	-0.18	31	31
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.006	0.23	-10000	0	-0.94	45	45
mol:DAG	-0.008	0.1	-10000	0	-0.41	41	41
RAP1A/GDP	0.015	0.019	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.013	0.12	-10000	0	-0.58	38	38
cytotoxic T cell degranulation	0.001	0.21	-10000	0	-1	35	35
RAP1A/GTP	-0.003	0.013	-10000	0	-0.069	23	23
mol:PI-3-4-5-P3	0.026	0.14	-10000	0	-0.57	42	42
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.011	0.18	0.29	158	-0.62	40	198
NRAS	-0.001	0.013	-10000	0	-10000	0	0
ZAP70	-0.03	0.13	-10000	0	-0.8	20	20
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.027	0.14	-10000	0	-0.63	41	41
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.033	0.14	-10000	0	-0.58	52	52
CARD11	-0.007	0.052	-10000	0	-0.34	21	21
PRKCB	-0.012	0.085	-10000	0	-0.34	44	44
PRKCE	-0.007	0.07	-10000	0	-0.29	34	34
PRKCQ	0.023	0.18	-10000	0	-0.7	44	44
LCP2	0	0.009	-10000	0	-0.29	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.032	0.1	-10000	0	-0.4	39	39
IKK complex	0.041	0.045	-10000	0	-0.12	24	24
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.036	0.08	-10000	0	-0.3	34	34
PDPK1	0.034	0.12	-10000	0	-0.46	38	38
TCR/CD3/MHC I/CD8/Fyn	-0.006	0.24	-10000	0	-0.95	48	48

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.22	-9999	-0.48	271	271
TC10/GTP	-0.11	0.18	-9999	-0.42	256	256
Insulin Receptor/Insulin/IRS1/Shp2	-0.021	0.1	-9999	-0.5	43	43
HRAS	-0.002	0.025	-9999	-10000	0	0
APS homodimer	-0.013	0.059	-9999	-0.28	46	46
GRB14	-0.1	0.22	-9999	-0.8	77	77
FOXO3	-0.015	0.067	-9999	-0.68	9	9
AKT1	-0.057	0.13	-9999	-0.52	11	11
INSR	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.2	0.35	-9999	-0.8	256	256
CRK	0	0	-9999	-10000	0	0
PTPN1	0.033	0.03	-9999	-10000	0	0
CAV1	-0.12	0.23	-9999	-0.52	235	235
CBL/APS/CAP/Crk-II/C3G	-0.12	0.2	-9999	-0.46	256	256
Insulin Receptor/Insulin/IRS1/NCK2	-0.021	0.1	-9999	-0.5	43	43
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.097	-9999	-0.44	53	53
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.013	0.056	-9999	-10000	0	0
RPS6KB1	-0.008	0.14	-9999	-0.47	11	11
PARD6A	-0.002	0.024	-9999	-0.29	7	7
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.05	0.12	-9999	-0.49	10	10
HRAS/GTP	-0.016	0.076	-9999	-0.47	2	2
Insulin Receptor	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.02	0.093	-9999	-0.46	43	43
PRKCI	-0.013	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.062	0.14	-9999	-0.42	88	88
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.003	-9999	-10000	0	0
PI3K	-0.023	0.098	-9999	-0.44	53	53
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.002	0.017	-9999	-10000	0	0
AKT2	-0.057	0.13	-9999	-0.52	11	11
PRKCZ	-0.014	0.037	-9999	-0.61	1	1
SH2B2	-0.013	0.059	-9999	-0.29	46	46
SHC/SHIP	-0.018	0.088	-9999	-0.44	43	43
F2RL2	-0.057	0.15	-9999	-0.35	167	167
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.004	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.13	0.21	-9999	-0.49	256	256
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	-0.02	0.094	-9999	-0.47	43	43
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.009	0.076	-9999	-0.99	6	6
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.034	0.16	-9999	-0.8	43	43
p62DOK/RasGAP	0	0.003	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	-0.02	0.093	-9999	-0.46	43	43
GRB2	0	0.009	-9999	-10000	0	0
EIF4EBP1	-0.014	0.14	-9999	-0.46	23	23
PTPRA	0	0.001	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.014	0.066	-9999	-0.33	43	43
Insulin Receptor/Insulin/IRS1	-0.022	0.1	-9999	-0.51	43	43
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.025	0.074	-9999	-0.46	21	21

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.2	0.26	1	-0.57	151	152
AKT1	0.014	0.006	-10000	0	-10000	0	0
GSC	-0.039	0.3	-10000	0	-1.5	41	41
NKX2-5	-0.043	0.1	-10000	0	-0.28	157	157
muscle cell differentiation	0.006	0.049	0.77	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.005	0.04	-10000	0	-0.46	2	2
SMAD4	0.014	0.042	-10000	0	-0.84	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.2	0.26	-10000	0	-0.53	385	385
SMAD3/SMAD4/VDR	0.005	0.031	-10000	0	-0.44	2	2
MYC	-0.018	0.12	-10000	0	-0.81	23	23
CDKN2B	0.028	0.13	-10000	0	-1.5	7	7
AP1	-0.12	0.21	-10000	0	-0.42	308	308
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.016	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0	0.042	-10000	0	-0.35	1	1
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.04	0.11	-10000	0	-0.28	178	178
SMAD3/SMAD4/GR	-0.01	0.074	-10000	0	-0.57	16	16
GATA3	-0.035	0.15	-10000	0	-0.79	34	34
SKI/SIN3/HDAC complex/NCoR1	0.002	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.05	0.12	-10000	0	-0.53	45	45
endothelial cell migration	-0.009	0.039	-10000	0	-10000	0	0
MAX	0.001	0.004	-10000	0	-10000	0	0
RBBP7	-0.002	0.025	-10000	0	-0.29	8	8
RBBP4	0	0.025	-10000	0	-0.8	1	1
RUNX2	-0.004	0.033	-10000	0	-0.29	14	14
RUNX3	-0.006	0.063	-10000	0	-0.63	9	9
RUNX1	-0.001	0.025	-10000	0	-0.8	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.011	0.097	-10000	0	-0.8	15	15
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.05	0.08	-10000	0	-1.5	2	2
KAT2B	0	0.026	-10000	0	-0.8	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.027	0.07	-10000	0	-0.47	5	5
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.002	-10000	0	-10000	0	0
SERPINE1	0.009	0.039	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.002	0.038	-10000	0	-0.56	3	3
SMAD3/SMAD4/ATF3	-0.083	0.2	-10000	0	-0.57	149	149
SAP30	-0.001	0.018	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.005	0.023	-10000	0	-10000	0	0
JUN	-0.079	0.23	-10000	0	-0.41	308	308
SMAD3/SMAD4/IRF7	-0.016	0.064	-10000	0	-0.55	1	1
TFE3	0.017	0.006	-10000	0	-10000	0	0
COL1A2	0.028	0.1	-10000	0	-1.3	2	2
mesenchymal cell differentiation	0.004	0.034	0.55	1	-10000	0	1
DLX1	-0.053	0.13	-10000	0	-0.31	171	171
TCF3	0	0.009	-10000	0	-10000	0	0
FOS	-0.23	0.37	-10000	0	-0.8	307	307
SMAD3/SMAD4/Max	-0.002	0.029	-10000	0	-0.55	1	1
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0.001	0.006	-10000	0	-10000	0	0
LAMC1	0.042	0.048	-10000	0	-0.63	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.029	-10000	0	-0.55	1	1
IRF7	-0.027	0.085	-10000	0	-0.36	22	22
ESR1	-0.15	0.29	-10000	0	-0.57	276	276
HNF4A	-0.004	0.036	-10000	0	-0.29	16	16
MEF2C	0.003	0.092	-10000	0	-0.66	3	3
SMAD2-3/SMAD4	-0.003	0.034	-10000	0	-0.55	1	1
Cbp/p300/Src-1	0.003	0.023	-10000	0	-0.53	1	1
IGHV3OR16-13	-0.001	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.002	0.007	-10000	0	-10000	0	0
SKIL	-0.003	0.03	-10000	0	-0.29	11	11
HDAC1	0	0.002	-10000	0	-10000	0	0
HDAC2	0	0.002	-10000	0	-10000	0	0
SNIP1	0	0.002	-10000	0	-10000	0	0
GCN5L2	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.001	0.03	-10000	0	-0.54	1	1
MSG1/HSC70	-0.23	0.3	-10000	0	-0.61	385	385
SMAD2	0.014	0.021	-10000	0	-10000	0	0
SMAD3	0.014	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.035	0.036	-10000	0	-0.35	2	2
SMAD2/SMAD2/SMAD4	0.027	0.041	-10000	0	-1.1	1	1
NCOR1	0	0.025	-10000	0	-0.8	1	1
NCOA2	-0.034	0.16	-10000	0	-0.8	43	43
NCOA1	-0.001	0.025	-10000	0	-0.8	1	1
MYOD/E2A	-0.003	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.011	0.042	-10000	0	-0.42	2	2
IFNB1	0.014	0.087	-10000	0	-0.41	14	14
SMAD3/SMAD4/MEF2C	-0.025	0.072	-10000	0	-0.77	2	2
CITED1	-0.31	0.39	-10000	0	-0.78	399	399
SMAD2-3/SMAD4/ARC105	-0.001	0.029	-10000	0	-0.48	1	1
RBL1	-0.001	0.028	-10000	0	-0.46	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.044	0.064	-10000	0	-0.49	7	7
RUNX1-3/PEBPB2	-0.004	0.049	-10000	0	-0.61	6	6
SMAD7	-0.074	0.14	-10000	0	-0.58	10	10
MYC/MIZ-1	-0.013	0.093	-10000	0	-0.62	23	23
SMAD3/SMAD4	0.018	0.06	0.28	38	-0.45	1	39
IL10	0.019	0.12	-10000	0	-0.52	36	36
PIASy/HDAC complex	0.001	0.004	-10000	0	-10000	0	0
PIAS3	0.001	0.005	-10000	0	-10000	0	0
CDK2	0.002	0.008	-10000	0	-10000	0	0
IL5	0.015	0.11	-10000	0	-0.52	34	34
CDK4	0.001	0.015	-10000	0	-10000	0	0
PIAS4	0.001	0.004	-10000	0	-10000	0	0
ATF3	-0.12	0.28	-10000	0	-0.8	149	149
SMAD3/SMAD4/SP1	0	0.033	-10000	0	-0.52	2	2
FOXG1	-0.021	0.073	-10000	0	-0.29	71	71
FOXO3	0.025	0.036	-10000	0	-0.61	3	3
FOXO1	0.02	0.063	-10000	0	-0.61	10	10
FOXO4	0.026	0.008	-10000	0	-10000	0	0
heart looping	0.003	0.091	-10000	0	-0.65	3	3
CEBPB	0.012	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.029	0.079	-10000	0	-0.57	10	10
MYOD1	-0.004	0.033	-10000	0	-0.29	14	14
SMAD3/SMAD4/HNF4	-0.006	0.036	-10000	0	-0.69	1	1
SMAD3/SMAD4/GATA3	-0.023	0.11	-10000	0	-0.58	34	34
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.029	-10000	0	-0.28	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0	0.051	-10000	0	-0.54	7	7
SMAD3/SMAD4/SP1-3	0.003	0.03	-10000	0	-0.46	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0.019	0.013	-10000	0	-10000	0	0
SIN3B	0	0.002	-10000	0	-10000	0	0
SIN3A	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.008	0.089	-10000	0	-0.47	6	6
ITGB5	0.052	0.047	-10000	0	-0.42	1	1
TGIF/SIN3/HDAC complex/CtBP	0	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.071	0.19	-10000	0	-0.57	128	128
AR	-0.1	0.26	-10000	0	-0.8	127	127
negative regulation of cell growth	-0.026	0.074	-10000	0	-0.49	2	2
SMAD3/SMAD4/MYOD	-0.007	0.035	-10000	0	-0.55	1	1
E2F5	-0.006	0.04	-10000	0	-0.29	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.003	0.056	-10000	0	-0.55	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0	0.045	-10000	0	-0.34	4	4
TFDP1	-0.001	0.018	-10000	0	-0.29	4	4
SMAD3/SMAD4/AP1	-0.12	0.21	-10000	0	-0.42	308	308
SMAD3/SMAD4/RUNX2	-0.004	0.034	-10000	0	-0.55	1	1
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.002	0.036	-10000	0	-0.8	2	2

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.036	0.085	-9999	-0.44	35	35
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.07	-9999	-0.47	5	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.045	0.074	-9999	-10000	0	0
AP1	-0.15	0.22	-9999	-0.8	37	37
ILK	-0.006	0.11	-9999	-0.47	35	35
bone resorption	-0.037	0.11	-9999	-0.66	17	17
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.005	0.092	-9999	-0.42	35	35
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.017	0.099	-9999	-0.61	27	27
alphaV/beta3 Integrin/Osteopontin	-0.05	0.11	-9999	-0.53	35	35
MAP3K1	-0.007	0.11	-9999	-0.49	35	35
JUN	-0.007	0.075	-9999	-0.8	9	9
MAPK3	0.009	0.11	-9999	-0.44	35	35
MAPK1	0.009	0.11	-9999	-0.44	35	35
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.003	0.12	-9999	-0.52	37	37
ITGB3	-0.028	0.14	-9999	-0.74	39	39
NFKBIA	0.022	0.1	-9999	-0.42	35	35
FOS	-0.24	0.37	-9999	-0.8	307	307
CD44	-0.001	0.015	-9999	-0.29	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.021	0.1	-9999	-0.51	3	3
NF kappa B1 p50/RelA	-0.022	0.067	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.6	35	35
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.11	-9999	-0.48	35	35
VAV3	-0.002	0.11	-9999	-0.45	41	41
MAP3K14	-0.004	0.11	-9999	-0.48	35	35
ROCK2	-0.021	0.13	-9999	-0.8	27	27
SPP1	-0.074	0.12	-9999	-0.28	271	271
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.035	0.084	-9999	-0.46	14	14
MMP2	-0.076	0.21	-9999	-0.68	37	37

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.11	-9999	-0.78	21	21
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.025	-9999	-0.8	1	1
RAC1-CDC42/GTP/PAK family	-0.13	0.14	-9999	-0.28	468	468
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.025	-9999	-0.8	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.8	2	2
MAP3K12	0	0	-9999	-10000	0	0
FGR	0	0.009	-9999	-0.29	1	1
p38 alpha/TAB1	-0.006	0.033	-9999	-0.35	3	3
PRKG1	-0.052	0.2	-9999	-0.8	66	66
DUSP8	-0.003	0.044	-9999	-0.8	3	3
PGK/cGMP/p38 alpha	-0.031	0.1	-9999	-0.4	69	69
apoptosis	-0.006	0.032	-9999	-0.34	3	3
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.1	0.27	-9999	-0.8	134	134
PAK1	-0.006	0.042	-9999	-0.29	23	23
SRC	0	0.009	-9999	-0.29	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.018	0.067	-9999	-0.35	17	17
BLK	-0.041	0.11	-9999	-0.3	142	142
HCK	-0.003	0.031	-9999	-0.29	12	12
MAP2K3	0	0.009	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.015	-9999	-0.29	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.029	0.047	-9999	-0.38	3	3
positive regulation of innate immune response	0.024	0.072	-9999	-0.37	17	17
LCK	-0.02	0.1	-9999	-0.42	49	49
p38alpha-beta/MKP7	-0.011	0.053	-9999	-0.35	16	16
p38alpha-beta/MKP5	-0.011	0.053	-9999	-0.35	17	17
PGK/cGMP	-0.04	0.15	-9999	-0.62	66	66
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.059	0.14	-9999	-0.38	146	146
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.37	0.4	-9999	-0.8	468	468

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.005	0.036	-10000	0	-0.28	15	15
GNB1/GNG2	-0.015	0.049	-10000	0	-0.19	65	65
AKT1	0.05	0.073	-10000	0	-0.21	36	36
EGF	-0.17	0.33	-10000	0	-0.8	214	214
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.01	0.049	-10000	0	-0.39	3	3
mol:Ca2+	0.046	0.1	-10000	0	-0.3	61	61
LYN	-0.01	0.049	-10000	0	-0.39	3	3
RhoA/GTP	-0.009	0.03	-10000	0	-0.13	30	30
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.11	-10000	0	-0.35	61	61
GNG2	-0.009	0.087	-10000	0	-0.8	12	12
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.056	-10000	0	-0.54	6	6
G beta5/gamma2	-0.02	0.065	-10000	0	-0.28	41	41
PRKCH	0.048	0.11	-10000	0	-0.35	61	61
DNM1	-0.006	0.067	-10000	0	-0.8	7	7
TXA2/TP beta/beta Arrestin3	-0.004	0.028	-10000	0	-0.31	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.031	0.15	-10000	0	-0.72	44	44
G12 family/GTP	-0.022	0.074	-10000	0	-0.31	61	61
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.003	0.05	-10000	0	-0.8	4	4
RhoA/GTP/ROCK1	-0.001	0.017	-10000	0	-0.54	1	1
mol:GDP	-0.036	0.08	0.35	22	-10000	0	22
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
PRKG1	-0.052	0.2	-10000	0	-0.8	66	66
mol:IP3	0.047	0.12	-10000	0	-0.38	61	61
cell morphogenesis	-0.001	0.017	-10000	0	-0.53	1	1
PLCB2	0.044	0.16	-10000	0	-0.52	61	61
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.002	0.063	-10000	0	-0.39	8	8
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.01	0.05	-10000	0	-0.39	3	3
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.003	0.031	-10000	0	-0.29	12	12
PRKCB1	0.044	0.12	-10000	0	-0.38	61	61
GNAQ	-0.002	0.036	-10000	0	-0.8	2	2
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.046	0.16	-10000	0	-0.55	61	61
LCK	-0.013	0.073	-10000	0	-0.45	17	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.057	-10000	0	-0.35	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.035	-10000	0	-0.29	7	7
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.056	-10000	0	-0.34	1	1
MAPK14	0.051	0.08	-10000	0	-0.23	61	61
TGM2/GTP	0.046	0.14	-10000	0	-0.43	61	61
MAPK11	0.05	0.082	-10000	0	-0.25	36	36
ARHGEF1	0.038	0.062	-10000	0	-0.18	61	61
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.049	0.12	-10000	0	-0.4	61	61
RAB11/GDP	-0.001	0.013	-10000	0	-0.28	2	2
ICAM1	0.046	0.093	-10000	0	-0.28	61	61
cAMP biosynthetic process	0.043	0.12	-10000	0	-0.36	61	61
Gq family/GTP/EBP50	0	0.034	-10000	0	-0.32	3	3
actin cytoskeleton reorganization	-0.001	0.017	-10000	0	-0.53	1	1
SRC	-0.01	0.049	-10000	0	-0.39	3	3
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.031	0.11	-10000	0	-0.3	46	46
VCAM1	0.044	0.1	-10000	0	-0.32	61	61
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.056	-10000	0	-0.54	6	6
platelet activation	0.066	0.11	-10000	0	-0.31	61	61
PGI2/IP	-0.002	0.021	-10000	0	-0.19	12	12
PRKACA	-0.015	0.071	-10000	0	-0.38	37	37
Gq family/GDP/G beta5/gamma2	0.027	0.057	-10000	0	-0.53	6	6
TXA2/TP beta/beta Arrestin2	-0.006	0.055	-10000	0	-0.66	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.014	0.065	-10000	0	-0.35	37	37
mol:DAG	0.046	0.13	-10000	0	-0.42	61	61
EGFR	-0.3	0.39	-10000	0	-0.8	384	384
TXA2/TP alpha	0.047	0.15	-10000	0	-0.5	61	61
Gq family/GTP	-0.004	0.035	-10000	0	-0.28	15	15
YES1	-0.01	0.05	-10000	0	-0.37	5	5
GNAI2/GTP	-0.012	0.057	-10000	0	-0.43	4	4
PGD2/DP	-0.024	0.12	-10000	0	-0.55	44	44
SLC9A3R1	-0.025	0.081	-10000	0	-0.29	89	89
FYN	-0.011	0.053	-10000	0	-0.41	6	6
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.034	-10000	0	-0.35	8	8
PGK/cGMP	-0.035	0.13	-10000	0	-0.54	66	66
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.017	0.08	-10000	0	-0.57	12	12
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.041	0.13	-10000	0	-0.38	68	68
PRKCB	0.043	0.12	-10000	0	-0.37	72	72
PRKCE	0.049	0.11	-10000	0	-0.35	61	61
PRKCD	0.047	0.12	-10000	0	-0.38	61	61
PRKCG	0.044	0.12	-10000	0	-0.39	61	61
muscle contraction	0.05	0.15	-10000	0	-0.5	61	61
PRKCZ	0.052	0.11	-10000	0	-0.35	62	62
ARR3	-0.002	0.025	-10000	0	-10000	0	0
TXA2/TP beta	-0.013	0.064	-10000	0	-0.46	5	5
PRKCQ	0.036	0.14	-10000	0	-0.38	83	83
MAPKKK cascade	0.044	0.14	-10000	0	-0.48	61	61
SELE	0.038	0.12	-10000	0	-0.42	61	61
TP beta/GNAI2/GDP/G beta/gamma	-0.016	0.08	-10000	0	-0.57	12	12
ROCK1	-0.001	0.025	-10000	0	-0.8	1	1
GNA14	-0.014	0.088	-10000	0	-0.45	31	31
chemotaxis	0.045	0.18	-10000	0	-0.63	61	61
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.002	0.036	-10000	0	-0.8	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.058	0.075	-9999	-0.41	6	6
EPHB2	-0.005	0.039	-9999	-10000	0	0
Syndecan-2/TACI	-0.017	0.076	-9999	-0.53	18	18
LAMA1	-0.095	0.26	-9999	-0.79	123	123
Syndecan-2/alpha2 ITGB1	-0.12	0.21	-9999	-0.47	270	270
HRAS	-0.002	0.025	-9999	-10000	0	0
Syndecan-2/CASK	-0.002	0.03	-9999	-0.54	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.034	0.057	-9999	-0.64	3	3
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.027	-9999	-0.48	3	3
LAMA3	-0.2	0.35	-9999	-0.8	254	254
EZR	-0.001	0.015	-9999	-0.29	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.098	0.26	-9999	-0.8	125	125
Syndecan-2/MMP2	-0.007	0.07	-9999	-0.67	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.016	0.097	-9999	-0.61	26	26
dendrite morphogenesis	-0.005	0.035	-9999	-0.52	3	3
Syndecan-2/GM-CSF	-0.005	0.037	-9999	-0.53	3	3
determination of left/right symmetry	0.017	0.037	-9999	-0.61	3	3
Syndecan-2/PKC delta	-0.002	0.03	-9999	-0.53	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.036	-9999	-0.48	3	3
MAPK1	0.022	0.036	-9999	-0.48	3	3
Syndecan-2/RACK1	-0.003	0.027	-9999	-0.45	3	3
NF1	-0.001	0.025	-9999	-0.8	1	1
FGFR/FGF/Syndecan-2	0.017	0.037	-9999	-0.61	3	3
ITGA2	-0.02	0.13	-9999	-0.8	26	26
MAPK8	0.028	0.059	-9999	-0.56	10	10
Syndecan-2/alpha2/beta1 Integrin	-0.066	0.18	-9999	-0.51	131	131
Syndecan-2/Kininogen	-0.004	0.035	-9999	-0.53	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.026	-9999	-0.42	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.027	-9999	-0.49	3	3
extracellular matrix organization	-0.002	0.03	-9999	-0.52	3	3
actin cytoskeleton reorganization	-0.058	0.074	-9999	-0.41	6	6
Syndecan-2/Caveolin-2/Ras	-0.062	0.16	-9999	-0.49	125	125
Syndecan-2/Laminin alpha3	-0.13	0.23	-9999	-0.53	257	257
Syndecan-2/RasGAP	-0.002	0.026	-9999	-0.43	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.29	1	1
Syndecan-2 dimer	-0.005	0.035	-9999	-0.53	3	3
GO:0007205	0	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.024	-9999	-0.41	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.026	0.11	-9999	-0.4	67	67
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.016	0.097	-9999	-0.61	26	26
Syndecan-2/Synbindin	-0.002	0.03	-9999	-0.53	3	3
TGFB1	0	0.009	-9999	-0.29	1	1
CASP3	0.03	0.029	-9999	-0.48	3	3
FN1	-0.11	0.14	-9999	-0.29	404	404
Syndecan-2/IL8	-0.021	0.085	-9999	-0.53	23	23
SDC2	0.017	0.037	-9999	-0.61	3	3
KNG1	-0.004	0.034	-9999	-10000	0	0
Syndecan-2/Neurofibromin	-0.003	0.034	-9999	-0.53	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.006	0.042	-9999	-0.29	23	23
Syndecan-2/TGFB1	-0.002	0.03	-9999	-0.53	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.027	-9999	-0.49	3	3
Syndecan-2/Ezrin	-0.002	0.028	-9999	-0.48	3	3
PRKACA	0.03	0.033	-9999	-0.48	4	4
angiogenesis	-0.021	0.084	-9999	-0.53	23	23
MMP2	-0.008	0.079	-9999	-0.8	10	10
IL8	-0.033	0.13	-9999	-0.41	81	81
calcineurin-NFAT signaling pathway	-0.017	0.076	-9999	-0.53	18	18

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.006	0.045	-9999	-0.38	11	11
ELF1	-0.012	0.05	-9999	-0.38	14	14
CCNA2	-0.11	0.14	-9999	-0.29	406	406
PIK3CA	0.01	0.01	-9999	-0.28	1	1
JAK3	-0.004	0.033	-9999	-0.28	14	14
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
JAK1	0.01	0.026	-9999	-0.8	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.057	0.08	-9999	-0.61	8	8
SHC1	0.011	0.003	-9999	-10000	0	0
SP1	-0.005	0.043	-9999	-0.38	13	13
IL2RA	0.002	0.13	-9999	-1	14	14
IL2RB	-0.012	0.064	-9999	-0.31	40	40
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.018	0.088	-9999	-0.35	52	52
G1/S transition of mitotic cell cycle	0.005	0.14	-9999	-0.84	21	21
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.016	0.12	-9999	-1	13	13
LCK	-0.02	0.1	-9999	-0.42	49	49
GRB2	0	0.009	-9999	-10000	0	0
IL2	-0.002	0.027	-9999	-0.28	9	9
CDK6	-0.01	0.087	-9999	-0.73	14	14
CCND3	0.063	0.07	-9999	-0.58	5	5

×

TCGA08_retinoblastoma

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
CDKN2B	-0.004	0.066	-10000	0	-0.67	9	9
CDKN2C	0.006	0.039	-10000	0	-0.79	2	2
CDKN2A	-0.05	0.11	-10000	0	-0.3	172	172
CCND2	0.006	0.033	0.25	8	-0.16	12	20
RB1	-0.007	0.032	0.19	4	-0.25	8	12
CDK4	0.009	0.03	0.25	9	-10000	0	9
CDK6	0.006	0.038	0.27	8	-0.22	11	19
G1/S progression	-0.007	0.035	0.25	8	-0.19	4	12

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.004	0.11	-10000	0	-0.44	35	35
IKBKB	0.015	0.053	-10000	0	-0.26	3	3
AKT1	0.003	0.082	0.25	2	-0.27	22	24
IKBKG	0.018	0.055	-10000	0	-0.28	3	3
CALM1	-0.011	0.093	-10000	0	-0.45	29	29
PIK3CA	0	0.009	-10000	0	-0.29	1	1
MAP3K1	-0.009	0.15	-10000	0	-0.66	31	31
MAP3K7	0	0.009	-10000	0	-0.29	1	1
mol:Ca2+	-0.02	0.098	-10000	0	-0.48	29	29
DOK1	-0.001	0.018	-10000	0	-10000	0	0
AP-1	-0.042	0.11	-10000	0	-0.26	73	73
LYN	0	0	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.21	-10000	0	-0.64	111	111
CD22	-0.062	0.18	-10000	0	-0.55	95	95
CAMK2G	-0.003	0.088	-10000	0	-0.41	29	29
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.047	0.14	-10000	0	-0.78	15	15
GO:0007205	-0.02	0.1	-10000	0	-0.49	29	29
SYK	0	0.009	-10000	0	-10000	0	0
ELK1	-0.011	0.095	-10000	0	-0.46	29	29
NFATC1	-0.017	0.13	-10000	0	-0.57	33	33
B-cell antigen/BCR complex	-0.079	0.21	-10000	0	-0.64	111	111
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.009	0.1	-10000	0	-0.47	30	30
NFKBIA	0.016	0.02	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.058	0.16	-10000	0	-0.52	94	94
mol:GDP	-0.02	0.092	-10000	0	-0.46	29	29
PTEN	-0.002	0.036	-10000	0	-0.8	2	2
CD79B	-0.028	0.14	-10000	0	-0.6	48	48
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.027	0.16	-10000	0	-0.48	94	94
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
mol:IP3	-0.03	0.098	-10000	0	-0.5	29	29
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.22	-10000	0	-0.45	327	327
CHUK	0.018	0.055	-10000	0	-0.24	17	17
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.024	0.079	-10000	0	-0.48	17	17
PTPN6	-0.058	0.17	-10000	0	-0.51	96	96
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.07	0.17	-10000	0	-0.62	56	56
ubiquitin-dependent protein catabolic process	0.019	0.019	-10000	0	-10000	0	0
BTK	-0.004	0.006	-10000	0	-10000	0	0
CD19	-0.08	0.18	-10000	0	-0.54	92	92
MAP4K1	-0.013	0.066	-10000	0	-0.8	2	2
CD72	-0.008	0.052	-10000	0	-0.3	28	28
PAG1	-0.001	0.02	-10000	0	-10000	0	0
MAPK14	0.002	0.13	-10000	0	-0.54	30	30
SH3BP5	0	0	-10000	0	-10000	0	0
PIK3AP1	-0.011	0.11	-10000	0	-0.54	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.042	0.14	-10000	0	-0.48	80	80
RAF1	-0.001	0.098	-10000	0	-0.44	28	28
RasGAP/p62DOK/SHIP	-0.055	0.16	-10000	0	-0.5	94	94
CD79A	-0.082	0.22	-10000	0	-0.55	152	152
re-entry into mitotic cell cycle	-0.041	0.11	-10000	0	-0.27	69	69
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.083	-10000	0	-0.43	16	16
MAPK1	0.015	0.083	-10000	0	-0.43	16	16
CD72/SHP1	-0.055	0.16	-10000	0	-0.67	41	41
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0	0.13	-10000	0	-0.53	35	35
actin cytoskeleton organization	-0.025	0.15	-10000	0	-0.65	32	32
NF-kappa-B/RelA	0.043	0.032	-10000	0	-10000	0	0
Calcineurin	-0.021	0.072	-10000	0	-0.44	16	16
PI3K	-0.058	0.13	-10000	0	-0.53	41	41
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.032	0.11	-10000	0	-0.57	29	29
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.048	0.17	-10000	0	-0.83	34	34
DAPP1	-0.051	0.2	-10000	0	-0.97	34	34
cytokine secretion	-0.014	0.12	-10000	0	-0.52	33	33
mol:DAG	-0.03	0.098	-10000	0	-0.5	29	29
PLCG2	-0.002	0.037	-10000	0	-0.63	3	3
MAP2K1	0.008	0.091	-10000	0	-0.48	16	16
B-cell antigen/BCR complex/FcgammaRIIB	-0.07	0.19	-10000	0	-0.56	113	113
mol:PI-3-4-5-P3	-0.043	0.093	0.34	2	-0.37	36	38
ETS1	0.004	0.09	-10000	0	-0.49	19	19
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.057	0.16	-10000	0	-0.52	92	92
B-cell antigen/BCR complex/LYN	-0.058	0.19	-10000	0	-0.58	92	92
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0.001	-10000	0	-10000	0	0
RAC1	-0.028	0.16	-10000	0	-0.71	32	32
B-cell antigen/BCR complex/LYN/SYK	-0.058	0.18	-10000	0	-0.56	92	92
CARD11	-0.015	0.1	-10000	0	-0.49	29	29
FCGR2B	-0.003	0.051	-10000	0	-0.7	5	5
PPP3CA	-0.001	0.013	-10000	0	-0.29	2	2
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	-10000	0	-10000	0	0
PTPRC	-0.009	0.073	-10000	0	-0.47	20	20
PDPK1	-0.028	0.063	0.22	2	-0.27	22	24
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.014	-10000	0	-0.14	1	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.04	-9999	-0.19	40	40
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.046	0.13	-9999	-0.61	42	42
STXBP1	-0.005	0.061	-9999	-0.8	6	6
ACh/CHRNA1	-0.06	0.08	-9999	-0.27	9	9
RAB3GAP2/RIMS1/UNC13B	-0.038	0.11	-9999	-0.53	42	42
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.066	0.18	-9999	-0.42	159	159
mol:ACh	0.001	0.031	-9999	-0.15	33	33
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.037	0.093	-9999	-0.4	48	48
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.06	0.079	-9999	-0.27	9	9
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.096	0.14	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.059	0.12	-9999	-0.47	55	55
SNAP25	-0.016	0.068	-9999	-0.38	33	33
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.087	0.18	-9999	-0.37	241	241
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.009	0.05	-9999	-0.54	6	6
STX1A/SNAP25 fragment 1/VAMP2	-0.037	0.093	-9999	-0.4	48	48

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.025	0.03	-9999	-10000	0	0
BIRC5	-0.2	0.13	-9999	-0.29	732	732
NFKBIA	-0.023	0.033	-9999	-10000	0	0
CPEB1	-0.15	0.31	-9999	-0.8	192	192
AKT1	-0.023	0.033	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.023	0.032	-9999	-0.56	1	1
NDEL1/TACC3	-0.038	0.058	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.003	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.029	0.038	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-0.29	4	4
JUB	-0.003	0.05	-9999	-0.8	4	4
TPX2	-0.11	0.098	-9999	-10000	0	0
TP53	-0.011	0.016	-9999	-10000	0	0
DLG7	-0.03	0.036	-9999	-10000	0	0
AURKAIP1	-0.003	0.03	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.041	0.062	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.023	0.032	-9999	-0.55	1	1
AURKA	-0.037	0.044	-9999	-10000	0	0
AURKB	-0.006	0.009	-9999	-10000	0	0
CDC25B	-0.017	0.025	-9999	-10000	0	0
G2/M transition checkpoint	-0.024	0.04	-9999	-0.5	4	4
mRNA polyadenylation	-0.12	0.2	-9999	-0.53	191	191
Aurora A/CPEB	-0.12	0.2	-9999	-0.53	191	191
Aurora A/TACC1/TRAP/chTOG	-0.032	0.091	-9999	-0.48	39	39
BRCA1	-0.001	0.028	-9999	-0.46	3	3
centrosome duplication	-0.029	0.038	-9999	-10000	0	0
regulation of centrosome cycle	-0.038	0.057	-9999	-10000	0	0
spindle assembly	-0.031	0.09	-9999	-0.47	39	39
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.069	-9999	-0.62	1	1
CENPA	-0.002	0.011	-9999	-10000	0	0
Aurora A/PP2A	-0.025	0.03	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.007	0.028	-9999	-10000	0	0
negative regulation of DNA binding	-0.009	0.018	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.013	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.024	0.04	-9999	-0.5	4	4
mitotic prometaphase	-0.013	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.037	0.044	-9999	-10000	0	0
TACC1	-0.031	0.15	-9999	-0.8	39	39
TACC3	-0.043	0.1	-9999	-0.29	155	155
Aurora A/Antizyme1	-0.021	0.024	-9999	-10000	0	0
Aurora A/RasGAP	-0.025	0.03	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.003	0.003	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
GIT1/beta-PIX/PAK1	-0.004	0.023	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.1	0.098	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.087	-9999	-10000	0	0
PAK1	-0.006	0.042	-9999	-0.29	23	23
CKAP5	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.44	0.4	-10000	0	-0.8	560	560
CLTC	0.027	0.017	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	0.02	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.006	0.027	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.017	-10000	0	-0.27	1	1
CPE	0.005	0.083	-10000	0	-0.54	23	23
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.002	0.019	-10000	0	-10000	0	0
CTNND1	0.025	0.03	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.03	0.014	-10000	0	-10000	0	0
TSHR	-0.008	0.12	-10000	0	-0.54	45	45
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.007	0.076	-10000	0	-0.75	10	10
mol:Choline	-0.002	0.019	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.036	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.027	-10000	0	-10000	0	0
JUP	0.025	0.017	-10000	0	-0.27	1	1
ASAP2/amphiphysin II	-0.005	0.048	-10000	0	-0.49	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.016	0.054	-10000	0	-0.27	32	32
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.004	0.036	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.034	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.005	-10000	0	-10000	0	0
ACAP1	-0.001	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.021	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0.001	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.025	0.03	-10000	0	-10000	0	0
NME1	0.01	0.036	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.017	-10000	0	-10000	0	0
IL2RA	0.017	0.044	-10000	0	-0.32	14	14
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.22	0.2	-10000	0	-0.4	560	560
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.003	0.032	-10000	0	-0.34	9	9
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.014	-10000	0	-10000	0	0
SDC1	0.021	0.024	-10000	0	-0.35	1	1
ARF6/GDP	-0.007	0.032	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.035	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.019	-10000	0	-10000	0	0
endocytosis	0.005	0.048	0.48	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.076	0.2	-10000	0	-0.43	241	241
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.025	-10000	0	-0.8	1	1
Dynamin 2/GDP	-0.006	0.027	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.14	0.23	-10000	0	-0.43	385	385
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.008	0.03	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

Figure 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
HDAC1	0.001	0.004	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.01	0.077	-9999	-0.56	19	19
forebrain development	-0.025	0.2	-9999	-0.52	128	128
GNAO1	-0.029	0.14	-9999	-0.48	66	66
SMO/beta Arrestin2	-0.005	0.055	-9999	-0.62	8	8
SMO	0.004	0.073	-9999	-0.75	9	9
ARRB2	0.01	0.004	-9999	-10000	0	0
GLI3/SPOP	-0.002	0.035	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.002	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.036	0.17	-9999	-0.8	49	49
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.055	0.16	-9999	-0.5	86	86
SAP30	0	0.018	-9999	-0.29	4	4
mol:GDP	0.004	0.073	-9999	-0.75	9	9
MIM/GLI2A	0.002	0.029	-9999	-0.29	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.002	0.005	-9999	-10000	0	0
GLI2	0.04	0.037	-9999	-10000	0	0
GLI3	0.039	0.041	-9999	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.004	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.009	0.087	-9999	-0.8	12	12
Gi family/GTP	-0.023	0.095	-9999	-0.36	46	46
SIN3B	0.001	0.004	-9999	-10000	0	0
SIN3A	0.001	0.004	-9999	-10000	0	0
GLI3/Su(fu)	-0.003	0.026	-9999	-0.45	1	1
GLI2/Su(fu)	0.007	0.047	-9999	-0.39	6	6
FOXA2	-0.012	0.032	-9999	-10000	0	0
neural tube patterning	-0.025	0.2	-9999	-0.52	128	128
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.026	-9999	-0.46	1	1
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.002	0.029	-9999	-0.29	9	9
embryonic limb morphogenesis	-0.025	0.2	-9999	-0.52	128	128
SUFU	-0.003	0.029	-9999	-0.4	2	2
LGALS3	-0.01	0.09	-9999	-0.8	13	13
catabolic process	-0.005	0.028	-9999	-10000	0	0
GLI3A/CBP	-0.022	0.096	-9999	-0.38	68	68
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.027	0.21	-9999	-0.53	128	128
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.025	-9999	-0.8	1	1
RBBP7	-0.001	0.026	-9999	-0.29	8	8
Su(fu)/Galectin3	-0.009	0.066	-9999	-0.54	14	14
GNAZ	-0.005	0.075	-9999	-0.8	9	9
RBBP4	0	0.025	-9999	-0.8	1	1
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.004	0.027	-9999	-10000	0	0
STK36	0.011	0.026	-9999	-0.8	1	1
Gi family/GNB1/GNG2/GDP	-0.028	0.099	-9999	-0.57	16	16
PTCH1	-0.068	0.35	-9999	-1.1	92	92
MIM/GLI1	-0.053	0.19	-9999	-0.49	128	128
CREBBP	-0.022	0.096	-9999	-0.38	68	68
Su(fu)/SIN3/HDAC complex	0.006	0.021	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.017	0.094	-9999	-0.53	33	33
E-cadherin/beta catenin	-0.019	0.11	-9999	-0.61	32	32
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.001	0.027	-9999	-0.54	2	2
CDH1	-0.025	0.14	-9999	-0.8	32	32

×

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
SPHK2	0.022	0.02	-10000	0	-0.61	1	1
MAP4K4	0.041	0.047	-10000	0	-0.69	1	1
BAG4	-0.005	0.052	-10000	0	-0.4	13	13
PKC zeta/ceramide	-0.025	0.049	0.18	1	-0.58	1	2
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.08	-10000	0	-0.52	20	20
BAX	-0.009	0.022	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.01	-10000	0	-10000	0	0
BAD	-0.023	0.047	0.2	1	-0.25	1	2
SMPD1	0.025	0.034	-10000	0	-0.25	14	14
RB1	-0.024	0.048	0.2	1	-0.48	1	2
FADD/Caspase 8	0.048	0.048	-10000	0	-0.65	1	1
MAP2K4	-0.016	0.048	-10000	0	-0.46	2	2
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.016	0.047	-10000	0	-0.46	1	1
EGF	-0.17	0.33	-10000	0	-0.8	214	214
mol:ceramide	-0.035	0.049	0.21	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.021	0.023	-10000	0	-0.61	1	1
ASAH1	-0.001	0.015	-10000	0	-0.29	3	3
negative regulation of cell cycle	-0.024	0.048	0.2	1	-0.48	1	2
cell proliferation	-0.095	0.16	-10000	0	-0.39	225	225
BID	0.023	0.035	-10000	0	-0.4	1	1
MAP3K1	-0.024	0.048	0.2	1	-0.48	1	2
EIF2A	-0.006	0.042	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.003	0.044	-10000	0	-0.42	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.003	0.044	-10000	0	-0.42	1	1
Cathepsin D/ceramide	-0.029	0.051	0.18	1	-0.25	2	3
FADD	0.039	0.051	-10000	0	-0.47	3	3
KSR1	-0.024	0.049	0.2	1	-0.33	3	4
MAPK8	-0.013	0.055	0.2	1	-0.36	9	10
PRKRA	-0.023	0.046	0.2	1	-10000	0	1
PDGFA	-0.001	0.025	-10000	0	-0.8	1	1
TRAF2	-0.001	0.018	-10000	0	-10000	0	0
IGF1	-0.18	0.33	-10000	0	-0.8	225	225
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.034	0.049	0.21	1	-10000	0	1
CTSD	-0.01	0.053	-10000	0	-0.29	37	37
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.1	0.17	-10000	0	-0.42	225	225
PRKCD	0	0.009	-10000	0	-0.29	1	1
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.023	-10000	0	-0.61	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.001	0.025	-10000	0	-0.8	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.006	0.043	-10000	0	-0.73	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.072	-10000	0	-0.54	17	17
mol:Sphingosine-1-phosphate	0.022	0.02	-10000	0	-0.61	1	1
MAP2K1	-0.007	0.045	-10000	0	-0.43	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.008	0.045	0.18	25	-10000	0	25
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.004	0.038	-10000	0	-0.61	3	3
EIF2AK2	-0.015	0.044	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.01	0.064	-10000	0	-0.53	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.022	-10000	0	-0.33	1	1
MAP2K2	-0.007	0.045	-10000	0	-0.43	1	1
SMPD3	0.025	0.042	-10000	0	-0.27	17	17
TNF	-0.017	0.1	-10000	0	-0.49	36	36
PKC zeta/PAR4	-0.001	0.027	-10000	0	-0.61	2	2
mol:PHOSPHOCHOLINE	0.049	0.12	0.27	213	-10000	0	213
NF kappa B1/RelA/I kappa B alpha	-0.001	0.02	-10000	0	-0.45	2	2
AIFM1	-0.008	0.045	0.18	25	-10000	0	25
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.076	-10000	0	-0.75	10	10
positive regulation of NF-kappaB transcription factor activity	-0.065	0.19	-10000	0	-0.61	108	108
MAP2K4	0.041	0.04	-10000	0	-0.43	1	1
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.005	0.061	-10000	0	-0.8	6	6
SMPD1	-0.003	0.027	-10000	0	-0.29	9	9
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.078	0.24	-10000	0	-0.8	99	99
TRAIL/TRAILR2	-0.006	0.058	-10000	0	-0.61	9	9
TRAIL/TRAILR3	-0.009	0.072	-10000	0	-0.66	11	11
TRAIL/TRAILR1	-0.009	0.074	-10000	0	-0.61	15	15
TRAIL/TRAILR4	-0.065	0.19	-10000	0	-0.61	108	108
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.059	-10000	0	-0.49	15	15
IKK complex	-0.003	0.02	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0.006	-10000	0	-10000	0	0
MAPK3	0.017	0.06	-10000	0	-0.61	9	9
MAP3K1	-0.004	0.033	-10000	0	-0.32	10	10
TRAILR4 (trimer)	-0.078	0.24	-10000	0	-0.8	99	99
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.005	0.061	-10000	0	-0.8	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.04	-10000	0	-0.33	15	15
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.06	-10000	0	-0.61	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.008	0.056	-10000	0	-0.46	15	15
mol:ceramide	-0.003	0.027	-10000	0	-0.28	9	9
FADD	-0.004	0.034	-10000	0	-0.29	15	15
MAPK8	0.045	0.056	-10000	0	-0.45	8	8
TRAF2	-0.001	0.018	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.005	0.05	-10000	0	-0.43	11	11
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.067	-10000	0	-0.54	15	15
DAP3	0	0.009	-10000	0	-0.29	1	1
CASP10	0.021	0.11	0.31	94	-0.5	13	107
JNK cascade	-0.065	0.19	-10000	0	-0.61	108	108
TRAIL (trimer)	-0.007	0.075	-10000	0	-0.75	10	10
TNFRSF10C	-0.005	0.05	-10000	0	-0.43	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.009	0.057	-10000	0	-0.46	15	15
TRAIL/TRAILR2/FADD	-0.007	0.052	-10000	0	-0.53	9	9
cell death	-0.003	0.027	-10000	0	-0.28	9	9
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.031	-10000	0	-0.32	9	9
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.015	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.006	0.043	-10000	0	-0.45	9	9

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0.007	-10000	0	-10000	0	0
CDKN1B	0.036	0.025	-10000	0	-0.43	3	3
CDKN1A	0.036	0.021	-10000	0	-0.43	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
FOXO3	0.036	0.025	-10000	0	-0.43	3	3
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-10000	0	0
AKT3	0.009	0.057	-10000	0	-0.44	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.026	-10000	0	-0.42	4	4
BAD/YWHAZ	-0.001	0.009	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.025	0.4	4	-10000	0	4
TSC1	0.037	0.002	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-10000	0	0
AKT1/RAF1	0	0.001	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.037	0.002	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.021	0.045	-10000	0	-0.52	7	7
MAP3K5	-0.003	0.05	-10000	0	-0.8	4	4
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.021	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.002	-10000	0	-10000	0	0
CASP9	0.037	0.002	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.022	-10000	0	-0.4	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
AKT2/p21CIP1	-0.001	0.018	-10000	0	-0.41	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.003	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.054	0.029	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.036	0.009	-10000	0	-10000	0	0
MAPKKK cascade	0	0.001	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.005	-10000	0	-10000	0	0
TSC1/TSC2	0.044	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.005	-10000	0	-10000	0	0
glucose import	-0.25	0.26	-10000	0	-0.48	563	563
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.25	0.26	-10000	0	-0.48	563	563
GSK3A	0.037	0.002	-10000	0	-10000	0	0
FOXO1	0.032	0.046	-10000	0	-0.43	10	10
GSK3B	0.037	0.002	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.8	13	13
G1/S transition of mitotic cell cycle	0.044	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.043	0.031	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.023	0.076	0.32	35	-10000	0	35
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-10000	0	-0.54	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.031	0.14	-10000	0	-0.48	66	66
RhoA/GTP	-0.023	0.077	-10000	0	-0.33	35	35
negative regulation of cAMP metabolic process	-0.026	0.086	-10000	0	-0.36	35	35
GNAZ	-0.007	0.075	-10000	0	-0.8	9	9
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.059	-10000	0	-0.35	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.026	0.087	-10000	0	-0.37	35	35
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.039	0.17	-10000	0	-0.8	49	49

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.006	0.095	0.23	1	-0.46	33	34
ACTA1	-0.017	0.13	0.27	1	-0.66	32	33
NUMA1	0.006	0.095	0.23	1	-0.46	33	34
SPTAN1	-0.004	0.13	-10000	0	-0.64	31	31
LIMK1	-0.004	0.13	-10000	0	-0.64	31	31
BIRC3	-0.01	0.08	-10000	0	-0.52	20	20
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
CASP10	-0.015	0.15	-10000	0	-0.68	34	34
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.006	0.095	0.23	1	-0.46	33	34
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.003	0.12	-10000	0	-0.62	31	31
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.01	0.14	-10000	0	-0.64	40	40
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.013	0.089	-10000	0	-0.69	15	15
BID	0.005	0.062	-10000	0	-0.3	33	33
MAP3K1	0.004	0.042	-10000	0	-0.28	8	8
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.004	0.13	-10000	0	-0.64	31	31
CASP9	0.001	0.003	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	0.18	7	-0.22	5	12
neuron apoptosis	0.022	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.12	-10000	0	-0.61	31	31
APAF1	0	0.002	-10000	0	-10000	0	0
CASP6	0.023	0.057	-10000	0	-0.42	4	4
TRAF2	-0.001	0.018	-10000	0	-10000	0	0
ICAD/CAD	0.004	0.12	-10000	0	-0.61	31	31
CASP7	-0.007	0.037	0.35	9	-10000	0	9
KRT18	0.016	0.016	-10000	0	-10000	0	0
apoptosis	0.009	0.11	0.3	1	-0.54	31	32
DFFA	-0.004	0.13	-10000	0	-0.64	31	31
DFFB	-0.004	0.13	-10000	0	-0.64	31	31
PARP1	0.002	0.032	0.22	5	-0.18	7	12
actin filament polymerization	-0.003	0.12	0.57	34	-10000	0	34
TNF	-0.017	0.1	-10000	0	-0.49	36	36
CYCS	0.007	0.049	-10000	0	-0.22	31	31
SATB1	0.017	0.1	-10000	0	-0.48	29	29
SLK	-0.004	0.13	-10000	0	-0.64	31	31
p15 BID/BAX	-0.014	0.049	-10000	0	-0.35	8	8
CASP2	0.043	0.042	-10000	0	-0.46	1	1
JNK cascade	-0.004	0.042	0.27	8	-10000	0	8
CASP3	-0.013	0.13	0.29	1	-0.65	34	35
LMNB2	0.04	0.038	-10000	0	-0.35	3	3
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.025	-10000	0	-0.8	1	1
Mammalian IAPs/DIABLO	-0.005	0.046	-10000	0	-0.48	9	9
negative regulation of DNA binding	0.013	0.087	-10000	0	-0.68	15	15
stress fiber formation	-0.003	0.12	-10000	0	-0.62	31	31
GZMB	-0.028	0.15	-10000	0	-0.66	42	42
CASP1	0.014	0.035	-10000	0	-0.44	6	6
LMNB1	0.044	0.039	-10000	0	-0.35	3	3
APP	0.022	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.004	0.1	0.3	1	-0.52	31	32
LMNA	0.04	0.038	-10000	0	-0.35	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.037	-10000	0	-0.49	1	1
LRDD	-0.001	0.018	-10000	0	-10000	0	0
SREBF1	-0.006	0.13	-10000	0	-0.64	31	31
APAF-1/Caspase 9	-0.004	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.006	0.093	0.23	1	-0.45	33	34
CFL2	0.003	0.12	-10000	0	-0.59	34	34
GAS2	-0.051	0.19	-10000	0	-0.53	125	125
positive regulation of apoptosis	0.045	0.038	-10000	0	-0.38	2	2
PRF1	-0.018	0.11	-10000	0	-0.8	20	20

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.002	0.037	-10000	0	-0.63	3	3
ANTXR2	-0.009	0.083	-10000	0	-0.8	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.1	12	12
monocyte activation	0.003	0.075	-10000	0	-0.46	26	26
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.01	-10000	0	-10000	0	0
MAP2K7	-0.001	0.01	-10000	0	-10000	0	0
MAP2K6	-0.011	0.067	-10000	0	-0.48	20	20
CYAA	0.01	0.058	-10000	0	-0.5	12	12
MAP2K4	-0.002	0.018	-10000	0	-0.48	1	1
IL1B	0.006	0.069	-10000	0	-0.35	31	31
Channel	-0.006	0.059	-10000	0	-0.53	12	12
NLRP1	-0.008	0.06	-10000	0	-0.5	15	15
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.1	12	-10000	0	12
MAPK3	-0.001	0.01	-10000	0	-10000	0	0
MAPK1	-0.001	0.01	-10000	0	-10000	0	0
PGR	-0.14	0.21	-10000	0	-0.48	286	286
PA/Cellular Receptors	-0.007	0.064	-10000	0	-0.58	12	12
apoptosis	-0.001	0.011	-10000	0	-0.1	12	12
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.006	0.056	-10000	0	-0.5	12	12
macrophage activation	0.02	0.01	-10000	0	-10000	0	0
TNF	-0.017	0.1	-10000	0	-0.49	36	36
VCAM1	-0.012	0.073	-10000	0	-0.46	26	26
platelet activation	-0.001	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.014	0.021	0.11	21	-10000	0	21
IL18	0.01	0.037	-10000	0	-0.22	15	15
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.1	12	12
LEF	-0.001	0.011	-10000	0	-0.1	12	12
CASP1	-0.005	0.031	-10000	0	-0.24	15	15
mol:cAMP	-0.001	0.014	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.1	12	12
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.006	0.057	-10000	0	-0.51	12	12
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.031	0.14	-9999	-0.48	66	66
CDC42/GTP	-0.024	0.076	-9999	-0.37	10	10
PLCG1	-0.025	0.079	-9999	-0.32	37	37
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.024	0.075	-9999	-0.31	37	37
S1PR5	-0.008	0.059	-9999	-0.35	24	24
S1PR4	-0.015	0.081	-9999	-0.36	43	43
MAPK3	-0.025	0.079	-9999	-0.32	37	37
MAPK1	-0.025	0.079	-9999	-0.51	4	4
S1P/S1P5/Gi	-0.026	0.087	-9999	-0.37	35	35
GNAI1	-0.039	0.17	-9999	-0.8	49	49
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-9999	-0.54	3	3
RHOA	-0.007	0.04	-9999	-0.45	6	6
S1P/S1P4/Gi	-0.028	0.086	-9999	-0.35	37	37
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.075	-9999	-0.8	9	9
S1P/S1P4/G12/G13	-0.007	0.044	-9999	-0.49	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	0	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	-0.001	0.017	-10000	0	-0.53	1	1
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.038	0.039	-10000	0	-0.32	3	3
KAT2B	-0.001	0.025	-10000	0	-0.8	1	1
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.02	0.049	0.24	4	-0.34	11	15
RAR alpha/9cRA/Cyclin H	-0.011	0.064	-10000	0	-0.38	26	26
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.034	0.048	-10000	0	-0.32	13	13
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.012	0.068	-10000	0	-0.68	7	7
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.006	0.12	-10000	0	-0.59	28	28
NCOA2	-0.034	0.16	-10000	0	-0.8	43	43
NCOA3	0	0.009	-10000	0	-10000	0	0
NCOA1	-0.001	0.025	-10000	0	-0.8	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.009	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.067	-10000	0	-0.8	7	7
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.11	-10000	0	-0.63	26	26
RARA	0.014	0.062	-10000	0	-0.32	32	32
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.022	0.08	-10000	0	-0.29	54	54
PRKCA	-0.007	0.13	-10000	0	-0.8	26	26
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.005	0.13	-10000	0	-0.62	28	28
RXRG	-0.1	0.21	-10000	0	-0.45	272	272
RXRA	0.022	0.065	-10000	0	-0.33	32	32
RXRB	0.011	0.075	-10000	0	-0.44	26	26
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.024	0.095	-10000	0	-0.8	7	7
CRBP1/9-cic-RA	-0.017	0.069	-10000	0	-0.62	7	7
RARB	0.004	0.088	-10000	0	-0.8	12	12
PRKCG	-0.002	0.059	-10000	0	-0.28	43	43
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.12	-10000	0	-0.62	28	28
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.013	0.1	-10000	0	-0.49	30	30
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.056	-10000	0	-0.45	4	4
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.005	0.13	-10000	0	-0.62	28	28
positive regulation of DNA binding	-0.011	0.061	-10000	0	-0.36	26	26
NRIP1	-0.003	0.12	-10000	0	-0.86	8	8
RXRs/RARs	-0.012	0.13	-10000	0	-0.59	31	31
RXRs/RXRs/DNA/9cRA	-0.046	0.12	-10000	0	-0.66	26	26
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.006	0.035	-10000	0	-0.52	1	1
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.045	0.064	-10000	0	-0.52	5	5
UGCG	-0.011	0.095	-10000	0	-0.82	13	13
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.092	-10000	0	-0.39	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.014	0.097	-10000	0	-0.81	13	13
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.091	-10000	0	-0.4	34	34
FRAP1	0.052	0.13	-10000	0	-0.43	54	54
FOXO3	0.06	0.11	-10000	0	-0.57	11	11
AKT1	0.055	0.12	-10000	0	-0.45	32	32
GAB2	0.007	0.046	-10000	0	-0.38	11	11
SMPD1	-0.002	0.014	-10000	0	-10000	0	0
SGMS1	-0.002	0.014	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.056	-10000	0	-0.54	10	10
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.032	0.091	-10000	0	-0.36	35	35
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.006	0.061	-10000	0	-0.61	10	10
RPS6KB1	0.022	0.032	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	21	21
JAK3	0.009	0.035	-10000	0	-0.28	14	14
PIK3R1	0.005	0.081	-10000	0	-0.8	10	10
JAK1	0.012	0.026	-10000	0	-0.8	1	1
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.045	0.18	-10000	0	-0.94	28	28
MYB	0.01	0.18	-10000	0	-1.3	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.052	0.095	-10000	0	-0.59	10	10
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.022	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.052	0.093	-10000	0	-0.57	10	10
Rac1/GDP	-0.005	0.048	-10000	0	-0.49	10	10
T cell proliferation	0.058	0.088	-10000	0	-0.53	10	10
SHC1	0.011	0.004	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.01	-10000	0	-0.066	19	19
PRKCZ	0.058	0.091	-10000	0	-0.55	10	10
NF kappa B1 p50/RelA	-0.026	0.09	-10000	0	-0.53	12	12
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.039	0.069	-10000	0	-0.46	8	8
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.019	0.12	-10000	0	-0.8	14	14
IL2RB	0.001	0.066	-10000	0	-0.31	40	40
TERT	-0.04	0.1	-10000	0	-0.29	144	144
E2F1	0.023	0.064	-10000	0	-0.44	19	19
SOS1	0.011	0.004	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.03	19	-10000	0	19
PTPN11	0.011	0.004	-10000	0	-10000	0	0
IL2RG	-0.005	0.09	-10000	0	-0.35	52	52
actin cytoskeleton organization	0.058	0.088	-10000	0	-0.53	10	10
GRB2	0.01	0.01	-10000	0	-10000	0	0
IL2	0.006	0.028	-10000	0	-0.28	9	9
PIK3CA	0.013	0.01	-10000	0	-0.28	1	1
Rac1/GTP	0.026	0.05	-10000	0	-0.46	10	10
LCK	-0.008	0.1	-10000	0	-0.42	49	49
BCL2	0.038	0.2	-10000	0	-0.86	42	42

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0.009	-9999	-0.29	1	1
PLK4	-0.011	0.055	-9999	-0.29	40	40
regulation of centriole replication	0.014	0.04	-9999	-10000	0	0

×

IL1-mediated signaling events

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
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.007	0.044	-10000	0	-0.46	5	5
IRAK/TOLLIP	-0.001	0.009	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.031	0.12	-10000	0	-0.6	40	40
IL1A	-0.006	0.04	-10000	0	-0.29	20	20
IL1B	0.009	0.1	-10000	0	-0.73	17	17
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.014	-10000	0	-0.4	1	1
IL1R2	-0.038	0.16	-10000	0	-0.57	67	67
IL1R1	-0.016	0.11	-10000	0	-0.8	20	20
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.001	0.064	0.24	32	-0.33	17	49
TOLLIP	0	0.009	-10000	0	-0.29	1	1
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.032	0.08	-10000	0	-0.38	35	35
MAP3K7	0	0.009	-10000	0	-0.29	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.022	0.11	-10000	0	-0.49	45	45
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.012	0.073	-10000	0	-0.5	20	20
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.011	0.068	-10000	0	-0.47	20	20
IL1 beta fragment/IL1R1/IL1RAP	-0.02	0.11	-10000	0	-0.57	35	35
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.028	0.071	-10000	0	-0.4	27	27
IRAK1	0.021	0.012	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.02	0.094	-10000	0	-0.61	22	22
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.006	0.061	-10000	0	-0.61	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.011	0.064	-10000	0	-0.37	22	22
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.02	0.11	-10000	0	-0.57	35	35
IL1 beta/IL1R2	-0.034	0.14	-10000	0	-0.58	52	52
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.02	0.097	-10000	0	-0.9	5	5
IRAK3	-0.032	0.16	-10000	0	-0.79	41	41
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.018	0.1	-10000	0	-0.51	35	35
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.049	-10000	0	-0.34	20	20
IL1 alpha/IL1R1/IL1RAP	-0.014	0.08	-10000	0	-0.55	20	20
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0.009	-10000	0	-0.29	1	1
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0.007	-10000	0	-10000	0	0
IL1RAP	-0.001	0.025	-10000	0	-0.8	1	1
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.081	-10000	0	-0.8	5	5
CASP1	-0.004	0.056	-10000	0	-0.8	5	5
IL1RN/IL1R2	-0.035	0.12	-10000	0	-0.58	44	44
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.019	0.11	-10000	0	-0.54	35	35
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-0.29	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.008	0.054	-10000	0	-0.39	20	20
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL1RN	-0.012	0.064	-10000	0	-0.31	39	39
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.009	0.059	-10000	0	-0.42	20	20

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.03	0.007	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.045	-9999	-10000	0	0
MAPK12	0.018	0.079	-9999	-0.47	24	24
CCND1	0.016	0.04	-9999	-0.41	4	4
p38 gamma/SNTA1	-0.011	0.069	-9999	-0.46	20	20
MAP2K3	0	0.009	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.29	1	1
G2/M transition checkpoint	0.018	0.078	-9999	-0.47	24	24
MAP2K6	0.012	0.08	-9999	-0.5	24	24
MAPT	-0.016	0.13	-9999	-0.4	105	105
MAPK13	0.022	0.009	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.029	-9999	-0.44	4	4

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.019	0.1	-9999	-0.58	32	32
KLHL20	-0.009	0.033	-9999	-0.24	3	3
CYFIP2	-0.011	0.068	-9999	-0.35	32	32
Rac1/GDP	0.048	0.072	-9999	-0.35	32	32
ENAH	-0.019	0.1	-9999	-0.58	32	32
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.051	-9999	-0.5	1	1
ABI1/Sra1/Nap1	-0.006	0.025	-9999	-0.21	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.019	0.087	-9999	-0.48	34	34
RAPGEF1	0.037	0.094	-9999	-0.48	32	32
CTNND1	0	0.009	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.019	0.11	-9999	-0.6	32	32
CRK	0.028	0.1	-9999	-0.54	32	32
E-cadherin/gamma catenin/alpha catenin	-0.017	0.094	-9999	-0.53	33	33
alphaE/beta7 Integrin	-0.006	0.039	-9999	-0.61	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.038	-9999	-0.49	6	6
DLG1	-0.019	0.1	-9999	-0.58	32	32
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.041	-9999	-0.32	2	2
MLLT4	-0.005	0.062	-9999	-0.73	7	7
ARF6/GTP/NME1/Tiam1	-0.007	0.028	-9999	-10000	0	0
PI3K	-0.011	0.054	-9999	-0.43	2	2
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.11	-9999	-0.61	33	33
TIAM1	-0.001	0.018	-9999	-0.29	4	4
E-cadherin(dimer)/Ca2+	-0.014	0.079	-9999	-0.46	32	32
AKT1	-0.006	0.03	-9999	-0.24	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
CDH1	-0.025	0.14	-9999	-0.8	32	32
RhoA/GDP	0.047	0.072	-9999	-0.35	32	32
actin cytoskeleton organization	-0.006	0.025	-9999	-0.18	3	3
CDC42/GDP	0.047	0.072	-9999	-0.44	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.011	0.06	-9999	-0.34	33	33
ITGB7	-0.009	0.057	-9999	-0.32	27	27
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.015	0.084	-9999	-0.48	32	32
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.015	0.081	-9999	-0.46	32	32
mol:GDP	0.044	0.084	-9999	-0.41	32	32
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.001	0.027	-9999	-0.54	2	2
p120 catenin/RhoA/GDP	-0.011	0.062	-9999	-0.54	1	1
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.007	0.028	-9999	-0.21	6	6
NME1	-0.014	0.062	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.019	0.1	-9999	-0.57	33	33
regulation of cell-cell adhesion	-0.008	0.045	-9999	-0.42	1	1
WASF2	-0.003	0.013	-9999	-10000	0	0
Rap1/GTP	-0.011	0.059	-9999	-0.59	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.083	-9999	-0.45	35	35
CCND1	-0.009	0.034	-9999	-0.31	4	4
VAV2	0.032	0.099	-9999	-0.51	32	32
RAP1/GDP	-0.011	0.06	-9999	-0.57	1	1
adherens junction assembly	-0.018	0.098	-9999	-0.55	33	33
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.078	-9999	-0.42	35	35
E-cadherin/beta catenin	-0.016	0.086	-9999	-0.49	32	32
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.019	0.1	-9999	-0.58	32	32
PIK3CA	0	0.009	-9999	-0.29	1	1
Rac1/GTP	-0.012	0.054	-9999	-0.4	3	3
E-cadherin/beta catenin/alpha catenin	-0.017	0.092	-9999	-0.53	32	32
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.11	-9999	-0.62	32	32

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.05	-9999	-0.8	4	4
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.028	0.093	-9999	-0.34	80	80
GNAO1	-0.02	0.14	-9999	-0.48	66	66
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-10000	0	0
AKT1	-0.011	0.053	-9999	-0.68	4	4
AKT3	0.016	0.18	-9999	-1.4	16	16
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.05	-9999	-0.8	4	4
GNAI2	0.012	0.002	-9999	-10000	0	0
GNAI3	0.012	0.002	-9999	-10000	0	0
GNAI1	-0.027	0.18	-9999	-0.8	49	49
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.028	-9999	-0.29	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.1	-9999	-0.39	38	38
MAPK3	0.02	0.099	-9999	-0.51	13	13
MAPK1	0.02	0.099	-9999	-0.51	13	13
JAK2	0.022	0.1	-9999	-0.46	18	18
CXCR4	0.016	0.1	-9999	-0.48	18	18
FLT1	0.013	0.026	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.019	0.099	-9999	-0.51	13	13
S1P/S1P3/Gi	0.012	0.1	-9999	-0.4	38	38
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.023	0.083	-9999	-0.36	37	37
VEGFA	0.01	0.031	-9999	-0.34	1	1
S1P/S1P2/Gi	0.01	0.098	-9999	-0.37	37	37
VEGFR1 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.64	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.006	0.041	-9999	-0.34	15	15
GNAQ	-0.002	0.036	-9999	-0.8	2	2
GNAZ	0.005	0.076	-9999	-0.8	9	9
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.014	0.088	-9999	-0.45	31	31
GNA15	-0.003	0.034	-9999	-0.35	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.036	-9999	-0.8	2	2
Rac1/GTP	-0.023	0.083	-9999	-0.5	13	13

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.007	0.053	-9999	-0.33	22	22
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.002	0.017	-9999	-0.36	2	2
GNAO1	-0.031	0.14	-9999	-0.48	66	66
mol:Sphinganine-1-P	0.017	0.04	-9999	-0.61	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.027	-9999	-0.29	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.015	-9999	-0.31	2	2
S1PR5	-0.008	0.059	-9999	-0.35	24	24
S1PR4	-0.015	0.081	-9999	-0.36	43	43
GNAI1	-0.039	0.17	-9999	-0.8	49	49
S1P/S1P5/G12	-0.005	0.033	-9999	-0.47	3	3
S1P/S1P3/Gq	-0.004	0.036	-9999	-10000	0	0
S1P/S1P4/Gi	-0.026	0.083	-9999	-0.34	38	38
GNAQ	-0.002	0.036	-9999	-0.8	2	2
GNAZ	-0.007	0.075	-9999	-0.8	9	9
GNA14	-0.014	0.088	-9999	-0.45	31	31
GNA15	-0.003	0.034	-9999	-0.35	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.036	-9999	-0.8	2	2
ABCC1	0	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.017	0.085	-9999	-0.52	23	23
MAP4K1	-0.013	0.066	-9999	-0.8	2	2
MAP3K8	-0.005	0.062	-9999	-0.73	7	7
PRKCB	-0.019	0.11	-9999	-0.54	36	36
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.007	0.048	-9999	-0.47	4	4
JUN	0.016	0.12	-9999	-0.59	33	33
MAP3K7	-0.007	0.046	-9999	-0.49	3	3
GRAP2	-0.015	0.11	-9999	-0.8	18	18
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.043	0.057	-9999	-0.46	5	5
LAT	-0.006	0.049	-9999	-0.8	2	2
LCP2	0	0.009	-9999	-0.29	1	1
MAPK8	0.013	0.11	-9999	-0.69	24	24
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.05	-9999	-0.35	18	18
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.016	0.079	-9999	-0.5	21	21

×

BARD1 signaling events

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
BARD1/CSTF1	-0.01	0.077	-10000	0	-0.61	16	16
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.024	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.027	0.072	-10000	0	-0.49	17	17
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	-0.001	0.009	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.001	0.011	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-0.29	1	1
BRCA1	-0.001	0.028	-10000	0	-0.46	3	3
CCNE1	-0.057	0.11	-10000	0	-0.29	202	202
CDK2/Cyclin E1	-0.036	0.072	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.011	0.079	-10000	0	-0.61	17	17
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.05	0.11	-10000	0	-10000	0	0
DNA repair	0.009	0.092	-10000	0	-0.47	6	6
BRCA1/BARD1/ubiquitin	-0.011	0.079	-10000	0	-0.61	17	17
BARD1/DNA-PK	-0.008	0.06	-10000	0	-0.48	16	16
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.01	0.076	0.61	16	-10000	0	16
BRCA1/BARD1/CTIP/M/R/N Complex	-0.005	0.04	-10000	0	-0.32	16	16
BRCA1/BACH1/BARD1/TopBP1	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/P53	-0.008	0.062	-10000	0	-0.48	17	17
BARD1/CSTF1/BRCA1	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BACH1	-0.001	0.028	-10000	0	-0.46	3	3
BARD1	-0.013	0.1	-10000	0	-0.77	17	17
PCNA	-0.001	0.015	-10000	0	-0.29	3	3
BRCA1/BARD1/UbcH5C	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/UbcH7	-0.009	0.068	-10000	0	-0.53	17	17
BRCA1/BARD1/RAD51/PCNA	-0.052	0.084	-10000	0	-0.53	17	17
BARD1/DNA-PK/P53	-0.008	0.056	-10000	0	-0.45	16	16
BRCA1/BARD1/Ubiquitin	-0.011	0.079	-10000	0	-0.61	17	17
BRCA1/BARD1/CTIP	-0.008	0.062	-10000	0	-0.48	17	17
FA complex	-0.005	0.01	-10000	0	-10000	0	0
BARD1/EWS	-0.01	0.076	-10000	0	-0.61	16	16
RBBP8	0.022	0.006	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.008	0.061	0.48	17	-10000	0	17
BRCA1/BARD1	-0.027	0.073	-10000	0	-0.49	17	17
CSTF1	0	0.009	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.01	0.078	-10000	0	-0.62	16	16
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-10000	0	0
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.011	0.079	-10000	0	-0.61	17	17
EWSR1	0	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.018	0.081	0.33	1	-0.36	52	53
FRAP1	0.011	0.022	-10000	0	-10000	0	0
AKT1	-0.016	0.07	0.24	1	-0.3	52	53
INSR	0	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.013	0.054	-10000	0	-0.34	11	11
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.017	-10000	0	-10000	0	0
TSC2	0	0.001	-10000	0	-10000	0	0
RHEB/GDP	-0.011	0.047	-10000	0	-0.31	11	11
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.018	0.084	-10000	0	-0.42	43	43
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.021	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.018	0.044	-10000	0	-0.26	11	11
MAP3K5	0.009	0.028	-10000	0	-0.44	4	4
PIK3R1	-0.008	0.079	-10000	0	-0.8	10	10
apoptosis	0.009	0.028	-10000	0	-0.44	4	4
mol:LY294002	0	0	-10000	0	-0.002	43	43
EIF4B	0.025	0.04	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.007	0.029	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.02	0.086	-10000	0	-0.39	53	53
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.031	0.18	1	-10000	0	1
FKBP1A	0	0.009	-10000	0	-0.28	1	1
RHEB/GTP	-0.011	0.046	-10000	0	-0.3	11	11
mol:Amino Acids	0	0	-10000	0	-0.002	43	43
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.017	0.073	0.26	1	-0.33	52	53
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.004	0.04	-10000	0	-0.63	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.013	0.058	-10000	0	-0.36	11	11
tumor necrosis factor receptor activity	0	0	0.002	43	-10000	0	43
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	-0.011	0.092	-10000	0	-0.45	43	43
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.035	-10000	0	-0.8	2	2
PDK2	-0.018	0.079	0.26	1	-0.34	55	56
EIF4EBP1	0.013	0.013	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.28	1	1
PPP2R5D	0.018	0.02	-10000	0	-10000	0	0
peptide biosynthetic process	0	0.004	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-0.003	10	12
EEF2	0	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.004	0.024	-9999	-0.41	2	2
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin/MAdCAM1	-0.01	0.043	-9999	-0.46	3	3
EPO	-0.047	0.11	-9999	-0.29	169	169
alpha4/beta7 Integrin	-0.007	0.045	-9999	-0.44	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.03	0.067	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.041	-9999	-0.4	10	10
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.061	-9999	-0.61	10	10
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.009	0.025	-9999	-0.51	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
MADCAM1	-0.011	0.055	-9999	-0.29	40	40
cell adhesion	-0.01	0.042	-9999	-0.45	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.025	0.058	-9999	-0.48	12	12
ITGB7	-0.009	0.057	-9999	-0.32	27	27
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.059	-9999	-0.53	12	12
p130Cas/Crk/Dock1	-0.006	0.043	-9999	-10000	0	0
VCAM1	-0.011	0.089	-9999	-0.63	18	18
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.014	-9999	-10000	0	0
BCAR1	0.033	0.055	-9999	-0.44	12	12
EPOR	0	0.009	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
Rac1/GTP	-0.003	0.042	-9999	-0.42	10	10

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.049	0.029	-10000	0	-0.39	1	1
NFATC2	0.017	0.062	-10000	0	-0.3	9	9
NFATC3	-0.001	0.016	-10000	0	-0.51	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.011	0.097	-10000	0	-0.54	18	18
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.019	0.078	-10000	0	-0.49	17	17
BCL2/BAX	-0.022	0.12	-10000	0	-0.62	36	36
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.021	0.083	-10000	0	-0.52	17	17
Calcineurin A alpha-beta B1/BCL2	-0.028	0.15	-10000	0	-0.8	36	36
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.02	0.081	0.51	17	-10000	0	17
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.029	0.086	-10000	0	-0.29	103	103
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.015	0.097	-10000	0	-0.8	13	13
MAP3K8	-0.005	0.062	-10000	0	-0.73	7	7
NFAT4/CK1 alpha	-0.001	0.017	-10000	0	-0.39	2	2
MEF2D/NFAT1/Cbp/p300	-0.034	0.09	-10000	0	-0.32	81	81
CABIN1	0.011	0.098	-10000	0	-0.54	18	18
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.025	-10000	0	-0.8	1	1
CAMK4	-0.011	0.058	-10000	0	-0.3	36	36
mol:Ca2+	0	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.044	-10000	0	-0.61	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.006	0.066	-10000	0	-0.8	7	7
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-0.29	1	1
NFAT1-c-4/YWHAQ	-0.002	0.022	-10000	0	-0.41	1	1
PRKCH	-0.001	0.025	-10000	0	-0.8	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0	0	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-10000	0	-10000	0	0
apoptosis	-0.007	0.036	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.024	-10000	0	-10000	0	0
PRKCB	-0.019	0.11	-10000	0	-0.54	36	36
PRKCE	-0.001	0.025	-10000	0	-0.8	1	1
JNK2/NFAT4	0	0.015	-10000	0	-0.47	1	1
BAD/BCL-XL	0	0.006	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.29	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.025	-10000	0	-0.8	1	1
PRKCA	-0.021	0.13	-10000	0	-0.8	26	26
PRKCG	-0.012	0.057	-10000	0	-0.29	43	43
PRKCQ	-0.039	0.17	-10000	0	-0.71	56	56
FKBP38/BCL2	-0.022	0.11	-10000	0	-0.61	36	36
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.048	0.047	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.006	0.032	-10000	0	-0.54	1	1
NFATc/ERK1	0.049	0.033	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.019	0.078	-10000	0	-0.49	17	17
NR4A1	-0.005	0.21	-10000	0	-0.71	81	81
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.001	0.016	-10000	0	-0.51	1	1
NFAT1/CK1 alpha	-0.015	0.038	-10000	0	-0.27	6	6
RCH1/ KPNB1	-0.018	0.055	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.015	0.067	-10000	0	-0.3	52	52
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-10000	0	0
NFATc/p38 alpha	0.051	0.031	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.029	-10000	0	-0.47	4	4
TRAF2/ASK1	-0.003	0.035	-10000	0	-0.54	4	4
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.025	0.046	-10000	0	-0.39	3	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.062	-10000	0	-0.39	8	8
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.034	0.092	-10000	0	-0.29	121	121
TXN	0.008	0.005	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	0	0	-10000	0	-10000	0	0
GADD45B	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K6	-0.001	0.025	-10000	0	-0.8	1	1
MAP3K7	0	0.009	-10000	0	-0.29	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.003	0.043	-10000	0	-0.61	5	5
TAK1/TAB family	0.001	0.012	0.22	3	-10000	0	3
RAC1/OSM/MEKK3	0	0.005	-10000	0	-10000	0	0
TRAF2	-0.001	0.018	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.006	0.024	-10000	0	-0.4	1	1
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.071	0.21	-10000	0	-0.8	74	74
CCM2	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/CAMKIIB	-0.046	0.14	-10000	0	-0.54	74	74
MAPK11	-0.002	0.043	-10000	0	-0.8	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.043	0.13	-10000	0	-0.49	77	77
OSM/MEKK3	0	0.008	-10000	0	-10000	0	0
TAOK1	-0.003	0.092	-10000	0	-0.44	43	43
TAOK2	0.017	0	-10000	0	-10000	0	0
TAOK3	0.017	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.003	0.05	-10000	0	-0.8	4	4
MAP3K10	0	0.009	-10000	0	-0.29	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.002	0.033	-10000	0	-0.53	4	4
GADD45/MTK1/MTK1	-0.013	0.035	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.006	0.052	-10000	0	-0.48	12	12
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.013	-10000	0	-0.4	1	1
GATA1/HDAC4	-0.003	0.03	-10000	0	-0.61	1	1
GATA1/HDAC5	-0.003	0.022	-10000	0	-10000	0	0
GATA2/HDAC5	-0.018	0.1	-10000	0	-0.61	27	27
HDAC5/BCL6/BCoR	-0.003	0.04	-10000	0	-0.53	6	6
HDAC9	-0.01	0.077	-10000	0	-0.49	20	20
Glucocorticoid receptor/Hsp90/HDAC6	-0.008	0.064	-10000	0	-0.53	15	15
HDAC4/ANKRA2	-0.001	0.019	-10000	0	-0.61	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.025	0.13	-10000	0	-0.8	27	27
HDAC4/RFXANK	-0.001	0.023	-10000	0	-0.61	1	1
BCOR	-0.002	0.036	-10000	0	-0.8	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0.009	-10000	0	-10000	0	0
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.007	0.066	-10000	0	-0.61	12	12
Histones	-0.003	0.024	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.025	-10000	0	-0.8	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.019	-10000	0	-0.61	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.013	-10000	0	-10000	0	0
CAMK4	-0.011	0.058	-10000	0	-0.3	36	36
Tubulin/HDAC6	0	0.006	-10000	0	-10000	0	0
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.004	0.036	-10000	0	-0.29	16	16
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.012	0.097	-10000	0	-0.8	15	15
SUMO1/HDAC4	0	0.014	-10000	0	-0.44	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.019	-10000	0	-0.61	1	1
Tubulin	0	0.008	-10000	0	-10000	0	0
HDAC4/14-3-3 E	-0.001	0.019	-10000	0	-0.61	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.004	0.047	-10000	0	-0.61	6	6
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.017	-10000	0	-0.53	1	1
HDAC4/SRF	-0.006	0.034	-10000	0	-0.53	2	2
HDAC4/ER alpha	-0.11	0.22	-10000	0	-0.61	152	152
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.024	-10000	0	-10000	0	0
cell motility	0	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.003	0.05	-10000	0	-0.8	4	4
HDAC4/CaMK II delta B	-0.001	0.025	-10000	0	-0.8	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.29	-10000	0	-0.57	277	277
HDAC6/HDAC11	-0.001	0.011	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.001	0.025	-10000	0	-0.8	1	1
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.02	-10000	0	-0.45	2	2
GNG2	-0.009	0.087	-10000	0	-0.8	12	12
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.013	-10000	0	-0.29	2	2
HDAC11	-0.001	0.018	-10000	0	-0.29	4	4
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.001	0.02	-10000	0	-10000	0	0
nuclear import	0	0.014	0.44	1	-10000	0	1

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.009	0.057	-9999	-0.32	27	27
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin	-0.007	0.045	-9999	-0.44	6	6
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.011	0.037	-9999	-0.42	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.007	0.028	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.024	-9999	-0.53	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.006	0.04	-9999	-0.34	2	2
CaM/Ca2+	0.01	0.033	-9999	-0.39	2	2
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.035	-9999	-0.4	1	1
AKT1	-0.01	0.043	-9999	-0.46	2	2
MAP2K1	0.04	0.043	-9999	-0.4	1	1
MAP3K11	0.03	0.042	-9999	-0.39	2	2
IFNGR1	0.001	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.098	-9999	-0.41	24	24
Rap1/GTP	-0.004	0.015	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.005	0.037	-9999	-0.44	2	2
CEBPB	0.075	0.039	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.008	0.057	-9999	-1.2	1	1
STAT1	-0.011	0.035	-9999	-0.4	1	1
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.038	0.096	-9999	-0.28	141	141
PIK3CA	0	0.009	-9999	-0.29	1	1
STAT1 (dimer)/PIAS1	-0.009	0.031	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	0.01	0.035	-9999	-0.42	2	2
MAPK3	0.054	0.04	-9999	-10000	0	0
STAT1 (dimer)	-0.007	0.055	-9999	-0.6	1	1
MAPK1	0.054	0.04	-9999	-10000	0	0
JAK2	0	0.025	-9999	-0.8	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
JAK1	0	0.025	-9999	-0.8	1	1
CAMK2D	-0.002	0.043	-9999	-0.8	3	3
DAPK1	0.07	0.033	-9999	-10000	0	0
SMAD7	0.05	0.038	-9999	-10000	0	0
CBL/CRKL/C3G	-0.007	0.022	-9999	-10000	0	0
PI3K	0.004	0.052	-9999	-0.42	10	10
IFNG	-0.038	0.096	-9999	-0.28	141	141
apoptosis	0.053	0.029	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.008	0.047	-9999	-0.29	29	29
CAMK2B	-0.071	0.21	-9999	-0.8	74	74
FRAP1	0.039	0.055	-9999	-0.42	2	2
PRKCD	-0.01	0.044	-9999	-0.46	2	2
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.006	0.04	-9999	-0.34	2	2
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.046	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.009	0.033	-9999	-10000	0	0
SOCS1	0	0.05	-9999	-1.5	1	1
mol:GDP	-0.007	0.021	-9999	-10000	0	0
CASP1	0.049	0.046	-9999	-0.36	5	5
PTGES2	0	0.009	-9999	-10000	0	0
IRF9	0.058	0.019	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.048	-9999	-0.41	11	11
RAP1/GDP	-0.004	0.016	-9999	-10000	0	0
CBL	-0.009	0.028	-9999	-0.39	2	2
MAP3K1	0.031	0.045	-9999	-0.4	3	3
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.006	0.04	-9999	-0.34	2	2
PTPN11	-0.011	0.032	-9999	-0.42	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.005	0.052	-9999	-0.4	13	13
Caspase 8 (4 units)	-0.009	0.047	-9999	-1	1	1
NEF	-0.005	0.026	-9999	-0.22	8	8
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	0.034	0.084	-9999	-0.81	9	9
CYCS	0.041	0.059	-9999	-0.94	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.026	0.13	-9999	-0.7	30	30
MAP2K7	0.042	0.049	-9999	-0.81	1	1
protein ubiquitination	0.066	0.035	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.003	0.05	-9999	-0.8	4	4
BID	-0.01	0.052	-9999	-1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.034	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.05	-9999	-0.8	4	4
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.004	0.034	-9999	-0.29	15	15
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.034	-9999	-10000	0	0
MAPK8	0.045	0.06	-9999	-0.46	8	8
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.018	-9999	-0.29	4	4
TRAF2	-0.001	0.018	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.011	0.057	-9999	-0.34	19	19
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.032	-9999	-0.39	1	1
CHUK	0.067	0.037	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.005	0.048	-9999	-0.53	7	7
TCRz/NEF	-0.025	0.11	-9999	-0.53	38	38
TNF	-0.017	0.1	-9999	-0.49	36	36
FASLG	-0.006	0.14	-9999	-0.65	38	38
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.072	-9999	-0.54	17	17
CASP6	-0.004	0.032	-9999	-0.71	1	1
CASP7	0.073	0.077	-9999	-0.62	9	9
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.073	0.077	-9999	-0.62	9	9
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.004	0.038	-9999	-0.61	3	3
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.062	0.04	-9999	-10000	0	0
APAF-1/Caspase 9	-0.009	0.054	-9999	-0.51	9	9
BCL2	0.036	0.1	-9999	-0.43	41	41

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.028	-9999	-0.91	1	1
VEGFR1 homodimer/NRP1	-0.001	0.029	-9999	-0.92	1	1
mol:DAG	0.038	0.032	-9999	-0.65	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.029	-9999	-0.85	1	1
CaM/Ca2+	-0.001	0.028	-9999	-0.61	2	2
HIF1A	0	0.012	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.005	0.049	-9999	-0.72	1	1
PLCG1	0.038	0.033	-9999	-0.66	2	2
NOS3	0.062	0.033	-9999	-0.56	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.061	0.031	-9999	-0.54	2	2
FLT1	0.029	0.033	-9999	-1	1	1
PGF	-0.001	0.028	-9999	-0.46	3	3
VEGFR1 homodimer/NRP2/VEGFR121	-0.004	0.048	-9999	-0.79	3	3
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
eNOS/Hsp90	0.065	0.03	-9999	-0.65	1	1
endothelial cell proliferation	0.036	0.089	-9999	-0.65	5	5
mol:Ca2+	0.038	0.032	-9999	-0.64	2	2
MAPK3	0.04	0.083	-9999	-0.44	27	27
MAPK1	0.04	0.083	-9999	-0.44	26	26
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
PLGF homodimer	-0.001	0.028	-9999	-0.46	3	3
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.33	-9999	-0.8	217	217
VEGFA homodimer	-0.003	0.029	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.031	-9999	-0.91	1	1
platelet activating factor biosynthetic process	0.046	0.08	-9999	-1.1	1	1
PI3K	-0.006	0.052	-9999	-0.47	12	12
PRKCA	0.033	0.087	-9999	-0.47	27	27
PRKCB	0.034	0.078	-9999	-0.48	19	19
VEGFR1 homodimer/PLGF homodimer	-0.002	0.033	-9999	-0.72	2	2
VEGFA	-0.003	0.03	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.032	-9999	-0.65	2	2
RASA1	0.039	0.028	-9999	-0.84	1	1
NRP2	-0.003	0.044	-9999	-0.67	4	4
VEGFR1 homodimer	0.029	0.033	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.028	0.18	-9999	-0.64	6	6
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.052	-9999	-0.47	12	12
mol:L-citrulline	0.061	0.031	-9999	-0.54	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.028	-9999	-0.8	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.029	-9999	-0.85	1	1
CD2AP	0	0.009	-9999	-0.29	1	1
PI3K/GAB1	-0.005	0.049	-9999	-0.45	11	11
PDPK1	-0.005	0.048	-9999	-0.74	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.029	-9999	-0.85	1	1
mol:NADP	0.061	0.031	-9999	-0.54	2	2
HSP90AA1	0	0.009	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.002	0.027	-9999	-0.79	1	1
VEGFR1 homodimer/NRP2	-0.002	0.049	-9999	-0.8	3	3

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.058	0.078	-9999	-0.52	1	1
CRKL	0.028	0.049	-9999	-0.49	1	1
mol:DAG	-0.002	0.027	-9999	-0.39	1	1
HRAS	-0.006	0.022	-9999	-10000	0	0
MAPK8	0.011	0.067	-9999	-0.52	7	7
RAP1A	0.028	0.049	-9999	-0.49	1	1
GAB1	0.028	0.049	-9999	-0.49	1	1
MAPK14	0.015	0.051	-9999	-10000	0	0
EPO	-0.036	0.11	-9999	-0.28	169	169
PLCG1	-0.002	0.028	-9999	-0.4	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-0.28	1	1
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.066	-9999	-0.63	6	6
GAB1/SHC/GRB2/SOS1	-0.007	0.022	-9999	-0.42	1	1
EPO/EPOR (dimer)	-0.029	0.064	-9999	-10000	0	0
IRS2	0.009	0.11	-9999	-0.47	42	42
STAT1	0.048	0.057	-9999	-0.51	1	1
STAT5B	-0.004	0.045	-9999	-0.44	4	4
cell proliferation	0.02	0.063	-9999	-0.48	7	7
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.009	0.042	-9999	-0.43	4	4
TEC	0.027	0.057	-9999	-0.49	4	4
SOCS3	-0.005	0.061	-9999	-0.8	6	6
STAT1 (dimer)	0.048	0.057	-9999	-0.5	1	1
JAK2	0.011	0.026	-9999	-0.82	1	1
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
EPO/EPOR (dimer)/JAK2	0.055	0.041	-9999	-0.52	1	1
EPO/EPOR	-0.029	0.064	-9999	-10000	0	0
LYN	0.012	0.002	-9999	-10000	0	0
TEC/VAV2	-0.007	0.042	-9999	-0.46	4	4
elevation of cytosolic calcium ion concentration	0.012	0.01	-9999	-0.28	1	1
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.018	0.048	-9999	-10000	0	0
mol:IP3	-0.002	0.027	-9999	-0.39	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.029	0.094	-9999	-0.49	22	22
SH2B3	0.012	0.004	-9999	-10000	0	0
NFKB1	0.015	0.051	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.009	0.031	-9999	-0.32	7	7
PTPN6	0.021	0.051	-9999	-0.52	1	1
TEC/VAV2/GRB2	-0.01	0.035	-9999	-0.45	4	4
EPOR	0.012	0.01	-9999	-0.28	1	1
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.007	0.022	-9999	-0.43	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.002	0.037	-9999	-0.63	3	3
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.45	1	1
VAV2	0.028	0.049	-9999	-0.49	1	1
CBL	0.028	0.049	-9999	-0.49	1	1
SHC/Grb2/SOS1	0.005	0.029	-9999	-0.45	1	1
STAT5A	-0.006	0.057	-9999	-0.48	9	9
GRB2	0	0.009	-9999	-10000	0	0
STAT5 (dimer)	0.057	0.088	-9999	-0.57	5	5
LYN/PLCgamma2	-0.001	0.028	-9999	-0.61	2	2
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.05	-9999	-0.49	1	1
BCL2	0.034	0.2	-9999	-0.98	36	36

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.022	0.11	-9999	-0.61	35	35
AKT1	0.081	0.065	-9999	-0.7	5	5
PTK2B	-0.02	0.11	-9999	-1	6	6
VEGFR2 homodimer/Frs2	-0.007	0.076	-9999	-0.84	7	7
CAV1	-0.17	0.33	-9999	-0.8	217	217
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.007	0.071	-9999	-0.78	7	7
endothelial cell proliferation	0.083	0.082	-9999	-0.72	5	5
mol:Ca2+	0.051	0.068	-9999	-0.91	4	4
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.004	0.067	-9999	-0.98	4	4
RP11-342D11.1	0.043	0.068	-9999	-0.7	7	7
CDH5	-0.007	0.075	-9999	-0.8	9	9
VEGFA homodimer	-0.001	0.012	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.021	0.13	-9999	-0.78	27	27
HRAS/GDP	-0.003	0.052	-9999	-0.77	4	4
SH2D2A	-0.034	0.097	-9999	-0.8	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.002	0.05	-9999	-0.71	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.019	0.081	-9999	-0.74	9	9
VEGFR1 homodimer	-0.001	0.025	-9999	-0.8	1	1
SHC/GRB2/SOS1	-0.004	0.06	-9999	-0.88	4	4
GRB10	0.051	0.068	-9999	-0.91	4	4
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-10000	0	0
PAK1	-0.006	0.042	-9999	-0.29	23	23
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.09	-9999	-1.1	6	6
HRAS	-0.002	0.025	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.011	0.062	-9999	-0.58	6	6
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.006	0.065	-9999	-0.96	4	4
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.043	-9999	-0.8	3	3
Nck/Pak	-0.004	0.027	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.007	0.079	-9999	-0.81	8	8
mol:GDP	-0.004	0.057	-9999	-0.84	4	4
mol:NADP	0.074	0.047	-9999	-0.57	4	4
eNOS/Hsp90	0.075	0.044	-9999	-0.53	4	4
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:IP3	0.051	0.069	-9999	-0.94	4	4
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.027	-9999	-0.54	2	2
VEGFA	-0.003	0.029	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	0.056	0.096	-9999	-0.96	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.02	0.12	-9999	-1.1	6	6
PTPN6	-0.001	0.013	-9999	-0.29	2	2
EPAS1	-0.005	0.069	-9999	-0.78	7	7
mol:L-citrulline	0.074	0.047	-9999	-0.57	4	4
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.005	0.068	-9999	-0.98	4	4
VEGFR2 homodimer/VEGFA homodimer	-0.006	0.07	-9999	-0.78	7	7
VEGFR2/3 heterodimer	-0.007	0.087	-9999	-0.92	8	8
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.056	0.074	-9999	-0.99	4	4
VEGFR2 homodimer	0.029	0.085	-9999	-0.94	7	7
FLT1	-0.001	0.025	-9999	-0.8	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.052	0.078	-9999	-0.88	5	5
MAPK1	0.052	0.078	-9999	-0.88	5	5
VEGFA145/NRP2	-0.004	0.04	-9999	-0.66	3	3
VEGFR1/2 heterodimer	-0.006	0.081	-9999	-0.91	7	7
KDR	0.029	0.086	-9999	-0.95	7	7
VEGFA165/NRP1/VEGFR2 homodimer	-0.005	0.078	-9999	-1	5	5
SRC	0	0.009	-9999	-0.29	1	1
platelet activating factor biosynthetic process	0.054	0.08	-9999	-0.91	5	5
PI3K	-0.007	0.072	-9999	-0.93	5	5
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.006	0.071	-9999	-0.78	7	7
FES	0.05	0.075	-9999	-0.96	4	4
GAB1	-0.005	0.066	-9999	-0.99	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.071	-9999	-0.78	7	7
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.009	0.17	-9999	-0.55	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.007	0.072	-9999	-0.74	8	8
PI3K/GAB1	0.08	0.073	-9999	-0.73	5	5
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.001	0.066	-9999	-0.94	4	4
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.007	0.082	-9999	-0.86	8	8
HSP90AA1	0	0.009	-9999	-10000	0	0
CDC42	0.051	0.071	-9999	-0.96	4	4
actin cytoskeleton reorganization	-0.019	0.08	-9999	-0.73	9	9
PTK2	0.052	0.11	-9999	-1.1	5	5
EDG1	0.043	0.068	-9999	-0.7	7	7
mol:DAG	0.051	0.069	-9999	-0.94	4	4
CaM/Ca2+	-0.005	0.058	-9999	-0.85	4	4
MAP2K3	0.057	0.073	-9999	-0.9	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.004	0.067	-9999	-0.98	4	4
PLCG1	0.051	0.071	-9999	-0.96	4	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.005	0.069	-9999	-0.98	4	4
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.025	-9999	-0.8	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.006	0.071	-9999	-1	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.007	0.071	-9999	-0.78	7	7
cell migration	0.078	0.086	-9999	-0.8	5	5
mol:PI-3-4-5-P3	-0.006	0.064	-9999	-0.81	5	5
FYN	-0.002	0.036	-9999	-0.8	2	2
VEGFB/NRP1	-0.005	0.059	-9999	-0.86	4	4
mol:NO	0.074	0.047	-9999	-0.57	4	4
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.005	0.052	-9999	-0.77	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.004	0.067	-9999	-0.98	4	4
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.029	0.15	-9999	-0.75	39	39
NOS3	0.076	0.053	-9999	-0.67	4	4
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.019	0.1	-9999	-0.54	33	33
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.046	0.1	-9999	-1.1	4	4
PRKCB	0.048	0.099	-9999	-0.94	6	6
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.004	0.063	-9999	-0.7	7	7
VEGFR1/2 heterodimer/VEGFA homodimer	-0.007	0.077	-9999	-0.84	7	7
VEGFA165/NRP2	-0.004	0.04	-9999	-0.66	3	3
MAPKKK cascade	-0.003	0.054	-9999	-0.77	4	4
NRP2	-0.003	0.044	-9999	-0.67	4	4
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	-0.001	0.025	-9999	-0.8	1	1
FAK1/Paxillin	0.056	0.096	-9999	-0.96	5	5
MAP3K13	0.049	0.077	-9999	-0.96	4	4
PDPK1	0.074	0.063	-9999	-0.68	5	5

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.025	0.3	2	-0.4	1	3
DAPP1	0.036	0.051	-10000	0	-0.53	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.046	0.078	-10000	0	-0.54	10	10
mol:DAG	0.052	0.051	0.21	1	-0.28	6	7
HRAS	-0.002	0.025	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.003	0.026	-10000	0	-0.3	2	2
PLCG2	-0.002	0.037	-10000	0	-0.63	3	3
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	-0.001	0.023	0.27	2	-0.4	2	4
ARF1/GTP	-0.001	0.023	0.28	2	-0.38	2	4
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.025	-10000	0	-0.8	1	1
RAP1A/GTP	-0.001	0.022	0.25	2	-0.39	2	4
ADAP1	-0.003	0.033	0.26	2	-0.4	5	7
ARAP3	-0.001	0.023	0.26	2	-0.4	2	4
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.057	-10000	0	-0.3	35	35
ARHGEF6	-0.011	0.093	-10000	0	-0.8	14	14
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.012	-10000	0	-10000	0	0
FYN	-0.002	0.036	-10000	0	-0.8	2	2
ARF6	0	0	-10000	0	-10000	0	0
FGR	0	0.009	-10000	0	-0.29	1	1
mol:Ca2+	0.039	0.029	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
ZAP70	-0.03	0.13	-10000	0	-0.8	20	20
mol:IP3	0.047	0.038	-10000	0	-0.22	1	1
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.026	-10000	0	-0.3	2	2
RhoA/GDP	-0.002	0.023	0.28	2	-0.34	2	4
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.061	0.035	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
PLEKHA2	0.03	0.008	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.035	-10000	0	-0.78	2	2
HSP90AA1	0	0.009	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.022	0.3	2	-10000	0	2
RhoA/GTP	-0.001	0.021	0.25	2	-0.37	2	4
Src family/SYK family/BLNK-LAT	-0.01	0.056	-10000	0	-0.55	5	5
BLK	-0.041	0.11	-10000	0	-0.3	142	142
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.021	0.26	2	-0.37	2	4
HCK	-0.003	0.031	-10000	0	-0.29	12	12
CYTH3	-0.001	0.025	0.26	2	-0.38	3	5
CYTH2	-0.001	0.021	0.26	2	-0.37	2	4
KRAS	-0.001	0.012	-10000	0	-0.28	2	2
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.055	-10000	0	-0.56	9	9
SGK1	-0.004	0.056	-10000	0	-0.71	6	6
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.033	-10000	0	-0.28	4	4
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-10000	0	0
ARF6/GDP	-0.002	0.023	0.29	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.025	0.36	2	-0.39	2	4
ARAP3/RAP1A/GTP	-0.001	0.023	0.25	2	-0.4	2	4
VAV1	-0.003	0.045	-10000	0	-0.8	3	3
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.002	0.02	-10000	0	-0.4	2	2
PLEKHA1	0.03	0.018	-10000	0	-0.53	1	1
Rac1/GDP	-0.003	0.026	-10000	0	-0.3	2	2
LAT	-0.006	0.049	-10000	0	-0.8	2	2
Rac1/GTP	-0.005	0.046	-10000	0	-0.38	14	14
ITK	-0.02	0.088	-10000	0	-0.44	38	38
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.065	0.24	1	-0.4	6	7
LCK	-0.02	0.1	-10000	0	-0.42	49	49
BTK	-0.001	0.022	0.26	2	-0.37	2	4

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.001	0.025	-9999	-0.8	1	1
SMAD2	0.014	0.005	-9999	-10000	0	0
SMAD3	0.041	0	-9999	-10000	0	0
SMAD3/SMAD4	0.004	0.017	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.017	-9999	-0.53	1	1
SMAD2/SMAD2/SMAD4	-0.009	0.031	-9999	-0.53	1	1
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0.015	-9999	-0.48	1	1
MAP3K1	-0.001	0.025	-9999	-0.8	1	1
TRAP-1/SMAD4	-0.008	0.071	-9999	-0.61	14	14
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.01	0.09	-9999	-0.8	13	13
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-0.29	1	1
KPNA2	-0.029	0.086	-9999	-0.29	103	103
PIAS4	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0.008	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.006	0.057	-9999	-0.53	12	12
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.025	-9999	-10000	0	0
NFKBIA	0.024	0.035	-9999	-0.27	13	13
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0.017	0	-9999	-10000	0	0
REL	-0.009	0.087	-9999	-0.8	12	12
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.009	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0.006	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.035	-9999	-0.27	13	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.024	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.061	-9999	-0.61	10	10
NF kappa B1 p50/RelA	-0.004	0.03	-9999	-0.27	13	13
IKBKB	-0.001	0.013	-9999	-0.29	2	2
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-10000	0	0
I kappa B alpha/PIK3R1	-0.008	0.052	-9999	-0.44	10	10
cell death	-0.003	0.023	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.006	0.057	-9999	-0.53	12	12
LCK	-0.02	0.1	-9999	-0.42	49	49
BCL3	-0.001	0.013	-9999	-0.29	2	2

×

PDGFR-beta signaling pathway

Figure S118. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S118. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.004	0.047	-9999	-0.56	6	6
PDGFB-D/PDGFRB/SLAP	-0.004	0.042	-9999	-0.61	4	4
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.043	-9999	-0.52	4	4
AKT1	-0.011	0.05	-9999	-0.52	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.004	0.052	-9999	-0.59	6	6
PIK3CA	0	0.009	-9999	-0.29	1	1
FGR	-0.002	0.035	-9999	-0.51	4	4
mol:Ca2+	0.033	0.049	-9999	-0.68	4	4
MYC	0.039	0.14	-9999	-0.83	25	25
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.003	0.029	-9999	-0.43	4	4
LRP1/PDGFRB/PDGFB	-0.008	0.07	-9999	-0.6	13	13
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.05	-9999	-0.7	4	4
PTEN	-0.002	0.036	-9999	-0.8	2	2
GRB2	0	0.009	-9999	-10000	0	0
GRB7	-0.02	0.076	-9999	-0.8	1	1
PDGFB-D/PDGFRB/SHP2	-0.002	0.038	-9999	-0.61	4	4
PDGFB-D/PDGFRB/GRB10	-0.002	0.038	-9999	-0.61	4	4
cell cycle arrest	-0.004	0.042	-9999	-0.61	4	4
HRAS	-0.002	0.025	-9999	-10000	0	0
HIF1A	0.051	0.059	-9999	-0.48	2	2
GAB1	0.035	0.056	-9999	-0.68	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.039	0.054	-9999	-0.62	4	4
PDGFB-D/PDGFRB	-0.003	0.037	-9999	-0.54	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.038	-9999	-0.61	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.051	-9999	-0.58	6	6
positive regulation of MAPKKK cascade	-0.002	0.038	-9999	-0.61	4	4
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
mol:IP3	0.033	0.051	-9999	-0.71	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.015	0.062	-9999	-0.61	5	5
SHB	-0.001	0.027	-9999	-0.54	2	2
BLK	-0.002	0.052	-9999	-0.59	7	7
PTPN2	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.038	-9999	-0.61	4	4
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.039	0.064	-9999	-0.61	5	5
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.038	-9999	-0.61	4	4
LCK	-0.01	0.084	-9999	-0.64	16	16
PDGFRB	0.008	0.051	-9999	-0.81	4	4
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.035	-9999	-0.52	4	4
ABL1	0.034	0.051	-9999	-0.64	4	4
PDGFB-D/PDGFRB/CBL	0.034	0.062	-9999	-0.8	4	4
PTPN1	-0.002	0.03	-9999	-0.28	11	11
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.005	0.038	-9999	-10000	0	0
cell proliferation	0.04	0.12	-9999	-0.69	27	27
SLA	-0.003	0.027	-9999	-0.29	9	9
actin cytoskeleton reorganization	-0.003	0.029	-9999	-10000	0	0
SRC	-0.002	0.035	-9999	-0.51	4	4
PI3K	-0.013	0.056	-9999	-0.59	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.012	0.05	-9999	-0.53	5	5
SH2B2	-0.013	0.059	-9999	-0.29	46	46
PLCgamma1/SPHK1	0	0.053	-9999	-0.62	6	6
LYN	-0.002	0.035	-9999	-0.52	4	4
LRP1	-0.009	0.083	-9999	-0.8	11	11
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.002	0.043	-9999	-0.8	3	3
STAT5A	-0.006	0.071	-9999	-0.8	8	8
NCK1-2/p130 Cas	-0.003	0.028	-9999	-0.42	4	4
SPHK1	-0.007	0.053	-9999	-0.33	22	22
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.033	0.051	-9999	-0.71	4	4
PLCG1	0.033	0.052	-9999	-0.73	4	4
NHERF/PDGFRB	-0.015	0.052	-9999	-0.52	4	4
YES1	-0.003	0.04	-9999	-0.53	5	5
cell migration	-0.015	0.052	-9999	-0.52	4	4
SHC/Grb2/SOS1	-0.003	0.028	-9999	-0.42	4	4
SLC9A3R2	-0.001	0.018	-9999	-10000	0	0
SLC9A3R1	-0.025	0.081	-9999	-0.29	89	89
NHERF1-2/PDGFRB/PTEN	-0.013	0.049	-9999	-0.48	6	6
FYN	-0.004	0.063	-9999	-0.9	4	4
DOK1	0.005	0.037	-9999	-0.48	4	4
HRAS/GTP	-0.002	0.017	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.046	0.084	-9999	-0.44	27	27
PRKCD	0.03	0.037	-9999	-0.48	4	4
FER	0.024	0.07	-9999	-0.52	15	15
MAPKKK cascade	-0.002	0.028	-9999	-0.41	4	4
RASA1	0.03	0.036	-9999	-0.48	4	4
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.031	-9999	-0.44	4	4
PDGFB-D/PDGFRB/SHB	-0.003	0.043	-9999	-0.61	5	5
chemotaxis	0.034	0.049	-9999	-0.62	4	4
STAT1-3-5/STAT1-3-5	-0.008	0.057	-9999	-0.7	3	3
Bovine Papilomavirus E5/PDGFRB	-0.002	0.039	-9999	-0.62	4	4
PTPRJ	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.045	0.048	-10000	0	-0.55	1	1
BAG4	-0.005	0.052	-10000	0	-0.4	13	13
BAD	0.032	0.018	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.08	-10000	0	-0.52	20	20
BAX	0.031	0.02	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.013	-10000	0	-0.1	2	2
IKBKB	0.051	0.046	-10000	0	-0.51	1	1
MAP2K2	0.044	0.025	-10000	0	-0.47	1	1
MAP2K1	0.044	0.025	-10000	0	-0.47	1	1
SMPD1	0.021	0.013	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.05	0.05	-10000	0	-0.45	3	3
MAP2K4	0.038	0.026	-10000	0	-0.39	2	2
protein ubiquitination	0.053	0.046	-10000	0	-0.52	1	1
EnzymeConsortium:2.7.1.37	0.049	0.027	-10000	0	-0.49	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.039	0.025	-10000	0	-0.5	1	1
CRADD	0	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.018	-10000	0	-0.17	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.023	-10000	0	-0.41	1	1
TRADD	0	0	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.046	0.024	-10000	0	-0.46	1	1
MAPK1	0.046	0.024	-10000	0	-0.46	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.043	0.052	-10000	0	-0.47	3	3
KSR1	0.032	0.026	-10000	0	-0.53	1	1
MAPK8	0.041	0.047	-10000	0	-0.43	8	8
TRAF2	-0.001	0.018	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.051	0.046	-10000	0	-0.51	1	1
TNF R/SODD	-0.004	0.038	-10000	0	-0.61	3	3
TNF	-0.017	0.1	-10000	0	-0.49	36	36
CYCS	0.037	0.027	0.15	31	-10000	0	31
IKBKG	0.051	0.046	-10000	0	-0.51	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.038	0.05	-10000	0	-0.59	1	1
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.027	0.15	31	-10000	0	31
TNF/TNF R/SODD	-0.013	0.072	-10000	0	-0.54	17	17
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.027	0.013	-10000	0	-10000	0	0
NSMAF	0.045	0.047	-10000	0	-0.55	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.028	0.15	-10000	0	-0.8	36	36

×

HIF-2-alpha transcription factor network

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
MMP14	0	0.016	-10000	0	-10000	0	0
oxygen homeostasis	0.012	0.012	-10000	0	-10000	0	0
TCEB2	-0.007	0.043	-10000	0	-10000	0	0
TCEB1	-0.001	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.004	0.037	-10000	0	-0.46	1	1
EPO	0.15	0.15	-10000	0	-0.72	2	2
FIH (dimer)	0.023	0.012	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.3	1	1
SERPINE1	0.16	0.15	-10000	0	-0.68	4	4
FLT1	-0.003	0.08	-10000	0	-1	5	5
ADORA2A	0.14	0.16	-10000	0	-0.64	5	5
germ cell development	0.16	0.15	-10000	0	-0.66	6	6
SLC11A2	0.16	0.15	-10000	0	-0.68	4	4
BHLHE40	0.16	0.15	-10000	0	-0.81	5	5
HIF1AN	0.023	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.016	0.07	-10000	0	-0.5	2	2
ETS1	0.022	0.059	-10000	0	-0.81	5	5
CITED2	0.001	0.01	-10000	0	-10000	0	0
KDR	-0.006	0.11	-10000	0	-1.2	7	7
PGK1	0.16	0.15	-10000	0	-0.68	4	4
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.18	0.16	-10000	0	-0.77	5	5
EPAS1	0.095	0.081	-10000	0	-0.42	4	4
SP1	0.018	0.002	-10000	0	-10000	0	0
ABCG2	0.13	0.25	-10000	0	-0.7	71	71
EFNA1	0.16	0.15	-10000	0	-0.68	4	4
FXN	0.16	0.15	-10000	0	-0.67	4	4
POU5F1	0.16	0.15	-10000	0	-0.69	6	6
neuron apoptosis	-0.18	0.15	0.74	5	-10000	0	5
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0.001	0.081	-10000	0	-0.38	7	7
EGLN2	0.021	0.025	-10000	0	-0.3	1	1
EGLN1	0.022	0.029	-10000	0	-0.81	1	1
VHL/Elongin B/Elongin C	-0.004	0.022	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.009	-10000	0	-10000	0	0
SLC2A1	0.15	0.15	-10000	0	-0.66	5	5
TWIST1	0.14	0.2	-10000	0	-0.71	35	35
ELK1	0.019	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.009	0.063	-10000	0	-0.61	1	1
VEGFA	0.16	0.15	-10000	0	-0.71	4	4
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.005	0.058	-9999	-0.49	14	14
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.048	-9999	-0.41	14	14
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.024	-9999	-0.29	7	7
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.024	-9999	-10000	0	0
YY1/LSF	-0.001	0.018	-9999	-0.4	2	2
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.006	0.042	-9999	-0.36	14	14
I kappa B alpha/HDAC1	-0.004	0.029	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.005	0.037	-9999	-0.31	14	14
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.029	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.007	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.033	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.025	0.13	-9999	-0.8	27	27
GATA1	-0.004	0.036	-9999	-0.29	16	16
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.008	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.29	8	8
NPC	0	0	-9999	-10000	0	0
RBBP4	-0.001	0.025	-9999	-0.8	1	1
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.005	0.033	-9999	-10000	0	0
KAT2B	-0.001	0.025	-9999	-0.8	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.008	-9999	-10000	0	0
SIN3 complex	0	0.007	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.025	-9999	-0.8	1	1
YY1/HDAC3	-0.004	0.026	-9999	-10000	0	0
YY1/HDAC2	0	0.009	-9999	-0.3	1	1
YY1/HDAC1	0	0.009	-9999	-0.3	1	1
NuRD/MBD2 Complex (MeCP1)	0	0.006	-9999	-10000	0	0
PPARG	-0.093	0.17	-9999	-0.38	247	247
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.029	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.005	0.033	-9999	-0.28	14	14
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0.011	-9999	-0.35	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0.009	-9999	-0.29	1	1
STAT3	0.025	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.017	-9999	-0.47	1	1
YY1/SAP30/HDAC1	-0.001	0.011	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.033	-9999	-10000	0	0
histone deacetylation	0.046	0.008	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.025	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.018	0.082	-9999	-0.48	27	27
GATA1/HDAC1	-0.003	0.022	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.032	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.012	0.076	-9999	-0.61	14	14
SIN3/HDAC complex/Mad/Max	0	0.007	-9999	-10000	0	0
NuRD Complex	0	0.007	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.023	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.018	-9999	-0.48	1	1
GATA1/Fog1	-0.004	0.027	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.017	0.1	-9999	-0.49	36	36
negative regulation of cell growth	0.046	0.009	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.05	-9999	-0.43	14	14
SIN3/HDAC complex/NCoR1	0	0.01	-9999	-10000	0	0
TFCP2	-0.001	0.025	-9999	-0.8	1	1
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0.009	-9999	-0.29	1	1
MBD2	0	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.029	0.037	-9999	-10000	0	0
PLK1	0.01	0.12	-9999	-0.61	8	8
CDKN1B	0.083	0.068	-9999	-0.54	3	3
FOXO3	0.043	0.11	-9999	-0.58	10	10
KAT2B	0.008	0.029	-9999	-0.84	1	1
FOXO1/SIRT1	0.007	0.038	-9999	-0.32	10	10
CAT	0.045	0.12	-9999	-1.1	5	5
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.032	0.04	-9999	-0.36	10	10
MAPK10	-0.04	0.18	-9999	-0.46	159	159
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.064	0.088	-9999	-0.37	1	1
response to oxidative stress	0.005	0.012	-9999	-10000	0	0
FOXO3A/SIRT1	-0.015	0.067	-9999	-0.52	8	8
XPO1	0	0	-9999	-10000	0	0
EP300	0.009	0.005	-9999	-10000	0	0
BCL2L11	0.029	0.019	-9999	-10000	0	0
FOXO1/SKP2	-0.003	0.032	-9999	-0.32	10	10
mol:GDP	0.005	0.012	-9999	-10000	0	0
RAN	0.012	0.001	-9999	-10000	0	0
GADD45A	0.069	0.062	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.069	0.027	-9999	-10000	0	0
MST1	-0.003	0.094	-9999	-0.66	18	18
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.002	0.039	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.034	0.041	-9999	-0.45	7	7
MAPK9	0.037	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.015	-9999	-10000	0	0
SIRT1	0.002	0.008	-9999	-10000	0	0
SOD2	0.093	0.074	-9999	-10000	0	0
RBL2	0.062	0.08	-9999	-0.55	2	2
RAL/GDP	0.011	0.016	-9999	-10000	0	0
CHUK	0.009	0.012	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.031	0.009	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.006	0.17	-9999	-1.5	12	12
SKP2	0	0	-9999	-10000	0	0
USP7	0.012	0.001	-9999	-10000	0	0
IKBKB	0.008	0.017	-9999	-0.27	2	2
CCNB1	0.036	0.12	-9999	-0.74	3	3
FOXO1-3a-4/beta catenin	-0.008	0.039	-9999	-0.4	5	5
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.032	-9999	-0.32	10	10
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.004	0.064	-9999	-0.81	6	6
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.068	0.078	-9999	-10000	0	0
SFN	-0.015	0.097	-9999	-0.8	13	13
CDK2	0.002	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.027	0.05	-9999	-10000	0	0
CREBBP	0.002	0.005	-9999	-10000	0	0
FBXO32	0.044	0.13	-9999	-1.2	6	6
BCL6	0.058	0.11	-9999	-1.1	5	5
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.028	-9999	-0.29	10	10
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.045	-9999	-0.44	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.014	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.032	-9999	-0.48	2	2
lamellipodium assembly	-0.004	0.046	-9999	-0.46	10	10
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.006	0.061	-9999	-0.61	10	10
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.008	0.079	-9999	-0.8	10	10
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
cell adhesion	-0.001	0.01	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.011	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.009	0.057	-9999	-0.32	27	27
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.007	0.05	-9999	-0.45	12	12
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.011	0.089	-9999	-0.63	18	18
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.012	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.001	0.012	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	-0.004	0.051	-9999	-0.52	10	10

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.077	0.036	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.007	0.038	-9999	-0.49	2	2
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-0.29	2	2
RIPK2	-0.001	0.02	-9999	-10000	0	0
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.003	0.047	-9999	-10000	0	0
NEMO/A20/RIP2	-0.001	0.02	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.008	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.009	0.054	-9999	-0.3	30	30
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.012	0.076	-9999	-0.61	14	14
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.021	0.13	-9999	-0.8	26	26
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.017	0.1	-9999	-0.49	36	36
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0	0.009	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.06	-9999	-10000	0	0

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.004	0.019	-9999	-10000	0	0
CLOCK	0.005	0.084	-9999	-0.8	11	11
TIMELESS/CRY2	-0.002	0.011	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.011	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.04	0.017	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.04	0.02	-9999	-10000	0	0
NPAS2	0.008	0.069	-9999	-0.8	7	7
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.014	0.003	-9999	-10000	0	0
CHEK1	-0.007	0.044	-9999	-10000	0	0
mol:HEME	0.014	0.003	-9999	-10000	0	0
PER1	-0.014	0.11	-9999	-0.8	18	18
BMAL/CLOCK/NPAS2	-0.01	0.069	-9999	-0.52	18	18
BMAL1/CLOCK	0.042	0.054	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.004	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.02	-9999	-10000	0	0
mol:NADPH	0.014	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.01	0.062	-9999	-0.56	1	1
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.001	0.018	-9999	-0.29	4	4

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.51	9	9
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	-0.001	0.013	-9999	-0.29	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.12	0.15	-9999	-0.35	11	11
YWHAZ	-0.001	0.015	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.018	0.053	-9999	-0.61	7	7
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.003	0.028	-9999	-0.29	10	10
PRKCI	0	0.009	-9999	-0.29	1	1
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.032	0	-9999	-10000	0	0
PRKCZ	-0.001	0.025	-9999	-0.8	1	1
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.004	0.032	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.13	0.16	-9999	-0.39	11	11
STX4	0	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.015	0.097	-9999	-0.8	13	13
LNPEP	-0.006	0.071	-9999	-0.8	8	8
YWHAE	0	0	-9999	-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	0.029	0.043	-10000	0	-10000	0	0
regulation of axonogenesis	0.004	0.03	0.32	9	-10000	0	9
myoblast fusion	0.008	0.026	-10000	0	-10000	0	0
mol:GTP	-0.005	0.015	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.029	-10000	0	-10000	0	0
ARF1/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GM1	0.006	0.014	-10000	0	-10000	0	0
mol:Choline	0.021	0.052	-10000	0	-0.52	9	9
lamellipodium assembly	-0.004	0.031	-10000	0	-10000	0	0
MAPK3	0.021	0.023	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.008	0.029	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.026	-10000	0	-10000	0	0
ARF1/GDP	-0.004	0.024	-10000	0	-10000	0	0
ARF6	0.007	0.007	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
TIAM1	0.011	0.019	-10000	0	-0.28	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.023	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.021	-10000	0	-10000	0	0
KALRN	-0.011	0.069	-10000	0	-0.48	20	20
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.021	-10000	0	-10000	0	0
NME1	-0.003	0.064	-10000	0	-10000	0	0
Rac1/GDP	-0.006	0.021	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.015	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.031	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.015	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.015	-10000	0	-10000	0	0
RhoA/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.029	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.011	0.058	-10000	0	-0.59	9	9
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.031	-10000	0	-10000	0	0
ruffle organization	-0.004	0.03	-10000	0	-0.32	9	9
regulation of epithelial cell migration	-0.005	0.015	-10000	0	-10000	0	0
PLD2	0.016	0.013	-10000	0	-10000	0	0
PIP5K1A	-0.004	0.03	-10000	0	-0.32	9	9
mol:Phosphatidic acid	0.021	0.052	-10000	0	-0.52	9	9
Rac1/GTP	-0.004	0.032	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.023	0.076	-9999	-9999
TP53	-0.008	0.019	-9999	-9999
Senescence	-0.008	0.019	-9999	-9999
Apoptosis	-0.008	0.019	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.016	0.039	-9999	-9999
MDM4	0	0	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

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

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.008	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	-0.001	0.02	-9999	-0.29	5	5
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.003	-9999	-10000	0	0
CD4	0	0	-9999	-10000	0	0
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.01	0.016	-9999	-0.19	6	6
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.007	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.009	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.009	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.004	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0	0.001	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0.016	-9999	-0.19	6	6
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0.016	-9999	-0.19	6	6
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

Figure S131. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S131. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.01	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.017	-9999	-10000	0	0
RELB	-0.003	0.027	-9999	-10000	0	0
NFKB2	0	0.009	-9999	-0.29	1	1
NF kappa B2 p52/RelB	-0.001	0.015	-9999	-10000	0	0
regulation of B cell activation	-0.001	0.015	-9999	-10000	0	0

pid_entity	TCGA.S3.A6ZH	TCGA.S3.A6ZG	TCGA.S3.A6ZF	TCGA.PE.A5DE
109_MAP3K5	-0.27	0.054	0.054	0.041
47_PPARGC1A	-0.8	0	-0.8	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	-0.8	-0.8	0	0
131_RELN/VLDLR	-0.48	-0.48	-0.48	-0.48
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	-0.074	-0.074	-0.072	-0.1
84_STAT5A	-0.074	-0.074	-0.072	-0.1