PARADIGM pathway analysis of mRNASeq expression data - Brain Lower Grade Glioma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
IL23-mediated signaling events	115
Ephrin A reverse signaling	111
TCGA08_retinoblastoma	88
FOXM1 transcription factor network	86
IL12-mediated signaling events	83
Aurora B signaling	78
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	71
Effects of Botulinum toxin	69
Syndecan-1-mediated signaling events	68
E-cadherin signaling events	68

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
IL23-mediated signaling events	0.2484	115	6913	60	-0.7	0.014	1000	-1000	-0.14	-1000
Ephrin A reverse signaling	0.2397	111	780	7	-0.14	0	1000	-1000	-0.024	-1000
TCGA08_retinoblastoma	0.1901	88	704	8	-0.1	0.077	1000	-1000	-0.011	-1000
FOXM1 transcription factor network	0.1857	86	4421	51	-0.42	0.027	1000	-1000	-0.18	-1000
IL12-mediated signaling events	0.1793	83	7231	87	-0.57	0.12	1000	-1000	-0.12	-1000
Aurora B signaling	0.1685	78	5275	67	-0.35	0.014	1000	-1000	-0.073	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1533	71	4836	68	-0.48	0.22	1000	-1000	-0.11	-1000
Effects of Botulinum toxin	0.1490	69	1804	26	-0.2	0.014	1000	-1000	-0.061	-1000
Syndecan-1-mediated signaling events	0.1469	68	2329	34	-0.23	0.014	1000	-1000	-0.053	-1000
E-cadherin signaling events	0.1469	68	343	5	-0.12	0.014	1000	-1000	-0.046	-1000
TCR signaling in naïve CD8+ T cells	0.1425	66	6149	93	-0.22	0.072	1000	-1000	-0.077	-1000
IL4-mediated signaling events	0.1382	64	5869	91	-0.61	0.44	1000	-1000	-0.12	-1000
Signaling events mediated by the Hedgehog family	0.1339	62	3249	52	-0.19	0.16	1000	-1000	-0.074	-1000
Glypican 2 network	0.1166	54	218	4	-0.065	-0.018	1000	-1000	-0.028	-1000
Syndecan-4-mediated signaling events	0.1123	52	3536	67	-0.19	0.038	1000	-1000	-0.095	-1000
Thromboxane A2 receptor signaling	0.1102	51	5435	105	-0.22	0.061	1000	-1000	-0.058	-1000
Signaling events regulated by Ret tyrosine kinase	0.1058	49	4048	82	-0.18	0.014	1000	-1000	-0.076	-1000
Signaling mediated by p38-alpha and p38-beta	0.1058	49	2197	44	-0.14	0.014	1000	-1000	-0.046	-1000
a4b1 and a4b7 Integrin signaling	0.1037	48	244	5	-0.081	-0.034	1000	-1000	-0.033	-1000
amb2 Integrin signaling	0.0994	46	3792	82	-0.24	0.014	1000	-1000	-0.077	-1000
Endothelins	0.0972	45	4329	96	-0.2	0.014	1000	-1000	-0.076	-1000
Caspase cascade in apoptosis	0.0950	44	3318	74	-0.19	0.05	1000	-1000	-0.043	-1000
Glypican 1 network	0.0929	43	2070	48	-0.17	0.03	1000	-1000	-0.049	-1000
Visual signal transduction: Cones	0.0907	42	1608	38	-0.16	0.017	1000	-1000	-0.061	-1000
FOXA2 and FOXA3 transcription factor networks	0.0907	42	1966	46	-0.27	0.02	1000	-1000	-0.059	-1000
Reelin signaling pathway	0.0907	42	2378	56	-0.29	0.014	1000	-1000	-0.082	-1000
Visual signal transduction: Rods	0.0907	42	2187	52	-0.21	0.014	1000	-1000	-0.079	-1000
HIF-1-alpha transcription factor network	0.0886	41	3137	76	-0.19	0.09	1000	-1000	-0.079	-1000
EGFR-dependent Endothelin signaling events	0.0886	41	871	21	-0.11	0.014	1000	-1000	-0.063	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0864	40	3452	85	-0.14	0.014	1000	-1000	-0.066	-1000
Calcium signaling in the CD4+ TCR pathway	0.0864	40	1270	31	-0.18	0.014	1000	-1000	-0.076	-1000
p75(NTR)-mediated signaling	0.0842	39	4973	125	-0.16	0.014	1000	-1000	-0.085	-1000
Aurora C signaling	0.0842	39	277	7	-0.17	0	1000	-1000	-0.039	-1000
PDGFR-alpha signaling pathway	0.0842	39	1735	44	-0.17	0.028	1000	-1000	-0.051	-1000
Arf6 signaling events	0.0821	38	2364	62	-0.21	0.014	1000	-1000	-0.056	-1000
IL1-mediated signaling events	0.0821	38	2368	62	-0.19	0.065	1000	-1000	-0.083	-1000
Ras signaling in the CD4+ TCR pathway	0.0821	38	647	17	-0.13	0.021	1000	-1000	-0.038	-1000
Glucocorticoid receptor regulatory network	0.0799	37	4295	114	-0.45	0.25	1000	-1000	-0.06	-1000
PLK1 signaling events	0.0778	36	3068	85	-0.18	0.042	1000	-1000	-0.044	-1000
Osteopontin-mediated events	0.0756	35	1334	38	-0.13	0.016	1000	-1000	-0.096	-1000
IL6-mediated signaling events	0.0756	35	2625	75	-0.16	0.065	1000	-1000	-0.067	-1000
LPA receptor mediated events	0.0713	33	3446	102	-0.19	0.018	1000	-1000	-0.079	-1000
PLK2 and PLK4 events	0.0691	32	98	3	-0.017	-0.012	1000	-1000	-0.012	-1000
TCGA08_p53	0.0691	32	225	7	-0.078	0.05	1000	-1000	-0.013	-1000
Nongenotropic Androgen signaling	0.0691	32	1698	52	-0.1	0.033	1000	-1000	-0.05	-1000
BCR signaling pathway	0.0691	32	3259	99	-0.18	0.03	1000	-1000	-0.087	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0648	30	1146	37	-0.14	0.014	1000	-1000	-0.051	-1000
BMP receptor signaling	0.0626	29	2413	81	-0.18	0.05	1000	-1000	-0.084	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0605	28	1458	52	-0.19	0.026	1000	-1000	-0.057	-1000
Fc-epsilon receptor I signaling in mast cells	0.0583	27	2620	97	-0.19	0.041	1000	-1000	-0.074	-1000
Retinoic acid receptors-mediated signaling	0.0583	27	1592	58	-0.19	0.016	1000	-1000	-0.067	-1000
ErbB2/ErbB3 signaling events	0.0562	26	1722	65	-0.17	0.023	1000	-1000	-0.06	-1000
Coregulation of Androgen receptor activity	0.0562	26	2011	76	-0.14	0.028	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0562	26	1222	47	-0.16	0.016	1000	-1000	-0.043	-1000
Wnt signaling	0.0562	26	186	7	-0.036	-0.017	1000	-1000	-0.029	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0562	26	2306	88	-0.18	0.019	1000	-1000	-0.12	-1000
Rapid glucocorticoid signaling	0.0562	26	538	20	-0.18	0.014	1000	-1000	-0.033	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0562	26	3130	120	-0.21	0.13	1000	-1000	-0.067	-1000
LPA4-mediated signaling events	0.0540	25	308	12	-0.055	0.014	1000	-1000	-0.018	-1000
Regulation of nuclear SMAD2/3 signaling	0.0540	25	3484	136	-0.22	0.22	1000	-1000	-0.059	-1000
Syndecan-2-mediated signaling events	0.0540	25	1781	69	-0.17	0.037	1000	-1000	-0.047	-1000
S1P5 pathway	0.0540	25	437	17	-0.14	0.057	1000	-1000	-0.05	-1000
IL2 signaling events mediated by STAT5	0.0540	25	567	22	-0.098	0.019	1000	-1000	-0.042	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0497	23	783	34	-0.063	0.014	1000	-1000	-0.063	-1000
JNK signaling in the CD4+ TCR pathway	0.0497	23	394	17	-0.079	0.014	1000	-1000	-0.059	-1000
Cellular roles of Anthrax toxin	0.0475	22	860	39	-0.16	0.019	1000	-1000	-0.026	-1000
Presenilin action in Notch and Wnt signaling	0.0475	22	1372	61	-0.28	0.032	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class III	0.0475	22	911	40	-0.12	0.1	1000	-1000	-0.04	-1000
IL27-mediated signaling events	0.0475	22	1122	51	-0.16	0.019	1000	-1000	-0.073	-1000
Signaling events mediated by PTP1B	0.0454	21	1644	76	-0.16	0.02	1000	-1000	-0.071	-1000
IL2 signaling events mediated by PI3K	0.0454	21	1256	58	-0.096	0.033	1000	-1000	-0.076	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0432	20	1109	54	-0.16	0.029	1000	-1000	-0.094	-1000
Noncanonical Wnt signaling pathway	0.0432	20	539	26	-0.12	0.014	1000	-1000	-0.065	-1000
Integrins in angiogenesis	0.0432	20	1753	84	-0.095	0.014	1000	-1000	-0.082	-1000
Canonical Wnt signaling pathway	0.0432	20	1022	51	-0.28	0.1	1000	-1000	-0.056	-1000
Paxillin-dependent events mediated by a4b1	0.0410	19	709	36	-0.14	0.033	1000	-1000	-0.059	-1000
E-cadherin signaling in the nascent adherens junction	0.0410	19	1516	76	-0.12	0.014	1000	-1000	-0.077	-1000
ErbB4 signaling events	0.0389	18	1297	69	-0.16	0.043	1000	-1000	-0.083	-1000
Ceramide signaling pathway	0.0389	18	1391	76	-0.16	0.023	1000	-1000	-0.063	-1000
S1P1 pathway	0.0389	18	665	36	-0.099	0.014	1000	-1000	-0.048	-1000
TCGA08_rtk_signaling	0.0389	18	485	26	-0.14	0.029	1000	-1000	-0.02	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0389	18	1474	78	-0.065	0.04	1000	-1000	-0.067	-1000
Ephrin B reverse signaling	0.0367	17	853	48	-0.11	0.082	1000	-1000	-0.066	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0346	16	473	28	-0.14	0.024	1000	-1000	-0.04	-1000
Aurora A signaling	0.0346	16	995	60	-0.14	0.033	1000	-1000	-0.058	-1000
TRAIL signaling pathway	0.0346	16	772	48	-0.046	0.031	1000	-1000	-0.066	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0346	16	1367	83	-0.19	0.053	1000	-1000	-0.069	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0346	16	762	45	-0.16	0.03	1000	-1000	-0.075	-1000
E-cadherin signaling in keratinocytes	0.0346	16	696	43	-0.12	0.026	1000	-1000	-0.062	-1000
S1P4 pathway	0.0324	15	389	25	-0.14	0.029	1000	-1000	-0.05	-1000
Signaling mediated by p38-gamma and p38-delta	0.0302	14	221	15	-0.023	0.027	1000	-1000	-0.024	-1000
Syndecan-3-mediated signaling events	0.0302	14	511	35	-0.17	0.014	1000	-1000	-0.061	-1000
EPHB forward signaling	0.0302	14	1212	85	-0.11	0.037	1000	-1000	-0.087	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0302	14	1105	74	-0.16	0.063	1000	-1000	-0.087	-1000
Regulation of Telomerase	0.0302	14	1477	102	-0.14	0.046	1000	-1000	-0.099	-1000
Insulin-mediated glucose transport	0.0281	13	432	32	-0.12	0.035	1000	-1000	-0.067	-1000
Regulation of p38-alpha and p38-beta	0.0281	13	730	54	-0.11	0.014	1000	-1000	-0.054	-1000
Plasma membrane estrogen receptor signaling	0.0281	13	1171	86	-0.056	0.031	1000	-1000	-0.076	-1000
BARD1 signaling events	0.0259	12	732	57	-0.053	0.029	1000	-1000	-0.057	-1000
ceramide signaling pathway	0.0259	12	589	49	-0.16	0.021	1000	-1000	-0.038	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0259	12	420	33	-0.11	0.042	1000	-1000	-0.062	-1000
Regulation of Androgen receptor activity	0.0238	11	820	70	-0.14	0.033	1000	-1000	-0.06	-1000
EPO signaling pathway	0.0216	10	594	55	-0.12	0.057	1000	-1000	-0.083	-1000
Nectin adhesion pathway	0.0216	10	653	63	-0.12	0.048	1000	-1000	-0.073	-1000
Class I PI3K signaling events	0.0216	10	773	73	-0.11	0.029	1000	-1000	-0.064	-1000
p38 MAPK signaling pathway	0.0216	10	472	44	-0.075	0.021	1000	-1000	-0.059	-1000
Canonical NF-kappaB pathway	0.0194	9	364	39	-0.16	0.087	1000	-1000	-0.074	-1000
IFN-gamma pathway	0.0194	9	629	68	-0.23	0.062	1000	-1000	-0.086	-1000
Atypical NF-kappaB pathway	0.0194	9	283	31	-0.089	0.029	1000	-1000	-0.04	-1000
S1P3 pathway	0.0194	9	396	42	-0.034	0.029	1000	-1000	-0.04	-1000
Class IB PI3K non-lipid kinase events	0.0194	9	27	3	-0.003	0.003	1000	-1000	-0.018	-1000
Circadian rhythm pathway	0.0173	8	186	22	-0.016	0.033	1000	-1000	-0.044	-1000
HIF-2-alpha transcription factor network	0.0173	8	347	43	-0.1	0.1	1000	-1000	-0.073	-1000
Signaling events mediated by PRL	0.0173	8	303	34	-0.061	0.022	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class I	0.0151	7	750	104	-0.16	0.06	1000	-1000	-0.062	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0151	7	945	125	-0.074	0.078	1000	-1000	-0.085	-1000
VEGFR1 specific signals	0.0151	7	421	56	-0.091	0.042	1000	-1000	-0.067	-1000
Hedgehog signaling events mediated by Gli proteins	0.0130	6	404	65	-0.042	0.064	1000	-1000	-0.06	-1000
Arf6 downstream pathway	0.0130	6	269	43	-0.027	0.027	1000	-1000	-0.033	-1000
Insulin Pathway	0.0130	6	505	74	-0.18	0.038	1000	-1000	-0.081	-1000
PDGFR-beta signaling pathway	0.0130	6	582	97	-0.058	0.065	1000	-1000	-0.075	-1000
Signaling events mediated by HDAC Class II	0.0108	5	443	75	-0.17	0.04	1000	-1000	-0.057	-1000
FoxO family signaling	0.0108	5	347	64	-0.12	0.12	1000	-1000	-0.074	-1000
Arf6 trafficking events	0.0108	5	388	71	-0.12	0.048	1000	-1000	-0.07	-1000
IGF1 pathway	0.0086	4	260	57	-0.05	0.054	1000	-1000	-0.085	-1000
Class I PI3K signaling events mediated by Akt	0.0065	3	255	68	-0.12	0.055	1000	-1000	-0.051	-1000
Alternative NF-kappaB pathway	0.0043	2	28	13	-0.006	0.014	1000	-1000	-0.058	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0022	1	43	23	-0.013	0.051	1000	-1000	-0.064	-1000
mTOR signaling pathway	0.0022	1	65	53	-0.006	0.037	1000	-1000	-0.056	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	19	27	-0.004	0.037	1000	-1000	-0.052	-1000
Arf1 pathway	0.0000	0	20	54	-0.005	0.037	1000	-1000	-0.04	-1000
Total	NA	3671	202092	7203	-20	5.6	131000	-131000	-8.3	-131000

IL23-mediated signaling 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
CCL2	-0.61	0.56	-10000	0	-1.2	190	190
IL23A	-0.62	0.56	-10000	0	-1.2	185	185
NF kappa B1 p50/RelA/I kappa B alpha	-0.59	0.52	-10000	0	-1.1	188	188
positive regulation of T cell mediated cytotoxicity	-0.65	0.63	-10000	0	-1.3	192	192
ITGA3	-0.56	0.53	-10000	0	-1.1	175	175
IL17F	-0.36	0.33	-10000	0	-0.72	161	161
IL12B	-0.022	0.058	-10000	0	-0.55	4	4
STAT1 (dimer)	-0.62	0.6	-10000	0	-1.2	191	191
CD4	-0.55	0.51	-10000	0	-1.1	174	174
IL23	-0.6	0.53	-10000	0	-1.2	186	186
IL23R	-0.084	0.085	-10000	0	-0.52	1	1
IL1B	-0.66	0.61	-10000	0	-1.3	202	202
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.55	0.51	-10000	0	-1.1	176	176
TYK2	-0.001	0.018	-10000	0	-10000	0	0
STAT4	-0.16	0.26	-10000	0	-0.54	148	148
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.081	0.21	-10000	0	-0.55	78	78
IL12RB1	-0.047	0.16	-10000	0	-0.6	36	36
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.038	0.12	-10000	0	-0.44	36	36
IL23R/JAK2	-0.095	0.1	-10000	0	-0.51	1	1
positive regulation of chronic inflammatory response	-0.65	0.63	-10000	0	-1.3	192	192
natural killer cell activation	0.008	0.007	0.047	1	-10000	0	1
JAK2	0.008	0.018	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
NFKB1	0.011	0.003	-10000	0	-10000	0	0
RELA	0.011	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.57	0.5	-10000	0	-1.1	188	188
ALOX12B	-0.62	0.57	-10000	0	-1.3	169	169
CXCL1	-0.61	0.56	-10000	0	-1.2	192	192
T cell proliferation	-0.65	0.63	-10000	0	-1.3	192	192
NFKBIA	0.011	0.003	-10000	0	-10000	0	0
IL17A	-0.27	0.26	-10000	0	-0.57	119	119
PI3K	-0.6	0.53	-10000	0	-1.1	194	194
IFNG	-0.024	0.031	-10000	0	-0.098	17	17
STAT3 (dimer)	-0.57	0.49	-10000	0	-1.1	188	188
IL18R1	-0.054	0.18	-10000	0	-0.55	57	57
IL23/IL23R/JAK2/TYK2/SOCS3	-0.33	0.3	-10000	0	-0.67	132	132
IL18/IL18R	-0.1	0.21	-10000	0	-0.44	105	105
macrophage activation	-0.028	0.018	-10000	0	-0.044	174	174
TNF	-0.65	0.61	-10000	0	-1.3	193	193
STAT3/STAT4	-0.67	0.54	-10000	0	-1.2	217	217
STAT4 (dimer)	-0.68	0.6	-10000	0	-1.2	209	209
IL18	-0.029	0.15	-10000	0	-0.55	36	36
IL19	-0.55	0.51	-10000	0	-1.1	156	156
STAT5A (dimer)	-0.62	0.59	-10000	0	-1.2	187	187
STAT1	-0.002	0.09	-10000	0	-0.5	15	15
SOCS3	-0.12	0.24	-10000	0	-0.53	116	116
CXCL9	-0.64	0.57	-10000	0	-1.2	200	200
MPO	-0.64	0.57	-10000	0	-1.2	201	201
positive regulation of humoral immune response	-0.65	0.63	-10000	0	-1.3	192	192
IL23/IL23R/JAK2/TYK2	-0.7	0.74	-10000	0	-1.4	192	192
IL6	-0.62	0.57	-10000	0	-1.2	193	193
STAT5A	0	0.093	-10000	0	-0.6	11	11
IL2	0.006	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.007	0.047	1	-10000	0	1
CD3E	-0.63	0.57	-10000	0	-1.2	180	180
keratinocyte proliferation	-0.65	0.63	-10000	0	-1.3	192	192
NOS2	-0.57	0.53	-10000	0	-1.1	178	178

×

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.14	0.22	-9999	-0.45	146	146
EFNA5	-0.083	0.22	-9999	-0.56	79	79
FYN	-0.11	0.22	-9999	-0.4	146	146
neuron projection morphogenesis	-0.14	0.22	-9999	-0.45	146	146
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.14	0.22	-9999	-0.45	146	146
EPHA5	-0.13	0.25	-9999	-0.56	117	117

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.062	0.19	-10000	0	-0.55	62	62
CDKN2C	-0.021	0.13	-10000	0	-0.44	41	41
CDKN2A	-0.1	0.23	-10000	0	-0.55	96	96
CCND2	0.065	0.14	0.3	101	-0.14	2	103
RB1	-0.07	0.15	-10000	0	-0.32	96	96
CDK4	0.077	0.16	0.34	97	-10000	0	97
CDK6	0.069	0.16	0.33	99	-0.17	13	112
G1/S progression	0.057	0.16	0.32	97	-10000	0	97

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.22	0.65	-10000	0	-1.2	113	113
PLK1	-0.006	0.2	-10000	0	-1.5	4	4
BIRC5	-0.23	0.55	-10000	0	-1.5	69	69
HSPA1B	-0.24	0.66	-10000	0	-1.2	119	119
MAP2K1	0.023	0.052	-10000	0	-0.54	1	1
BRCA2	-0.24	0.68	-10000	0	-1.3	122	122
FOXM1	-0.38	0.95	-10000	0	-1.8	121	121
XRCC1	-0.22	0.65	-10000	0	-1.2	112	112
FOXM1B/p19	-0.39	0.57	0.43	4	-1.3	122	126
Cyclin D1/CDK4	-0.21	0.6	-10000	0	-1.1	117	117
CDC2	-0.24	0.69	-10000	0	-1.3	120	120
TGFA	-0.19	0.59	-10000	0	-1.1	118	118
SKP2	-0.22	0.66	-10000	0	-1.2	117	117
CCNE1	0.013	0.036	-10000	0	-0.51	2	2
CKS1B	-0.22	0.65	-10000	0	-1.2	112	112
RB1	-0.18	0.28	-10000	0	-0.76	60	60
FOXM1C/SP1	-0.3	0.76	-10000	0	-1.5	120	120
AURKB	-0.28	0.59	-10000	0	-1.5	87	87
CENPF	-0.26	0.7	-10000	0	-1.3	117	117
CDK4	0.003	0.088	-10000	0	-0.5	13	13
MYC	-0.19	0.58	-10000	0	-1	116	116
CHEK2	0.009	0.11	-10000	0	-0.57	13	13
ONECUT1	-0.23	0.64	-10000	0	-1.2	120	120
CDKN2A	-0.11	0.24	-10000	0	-0.58	96	96
LAMA4	-0.22	0.65	-10000	0	-1.2	116	116
FOXM1B/HNF6	-0.32	0.79	-10000	0	-1.5	122	122
FOS	-0.31	0.7	-10000	0	-1.2	154	154
SP1	0.015	0.006	-10000	0	-10000	0	0
CDC25B	-0.22	0.65	-10000	0	-1.2	111	111
response to radiation	0.007	0.042	-10000	0	-10000	0	0
CENPB	-0.22	0.65	-10000	0	-1.2	113	113
CENPA	-0.27	0.71	-10000	0	-1.3	123	123
NEK2	-0.29	0.73	-10000	0	-1.3	131	131
HIST1H2BA	-0.23	0.65	-10000	0	-1.2	112	112
CCNA2	-0.058	0.19	-10000	0	-0.55	61	61
EP300	0.009	0.057	-10000	0	-0.61	4	4
CCNB1/CDK1	-0.3	0.78	-10000	0	-1.5	113	113
CCNB2	-0.28	0.74	-10000	0	-1.4	128	128
CCNB1	-0.25	0.7	-10000	0	-1.3	111	111
ETV5	-0.25	0.66	-10000	0	-1.2	120	120
ESR1	-0.24	0.66	-10000	0	-1.2	123	123
CCND1	-0.21	0.62	-10000	0	-1.1	117	117
GSK3A	0.027	0.036	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.018	0.17	-10000	0	-0.4	64	64
CDK2	-0.001	0.095	-10000	0	-0.55	13	13
G2/M transition of mitotic cell cycle	0.007	0.049	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.42	0.59	-10000	0	-1.3	126	126
GAS1	-0.23	0.66	-10000	0	-1.2	113	113
MMP2	-0.23	0.66	-10000	0	-1.2	112	112
RB1/FOXM1C	-0.23	0.65	-10000	0	-1.2	119	119
CREBBP	0.014	0	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.12	0.17	-10000	0	-0.4	80	80
TBX21	-0.49	0.5	-10000	0	-1	180	180
B2M	0.009	0.053	-10000	0	-0.5	5	5
TYK2	0.001	0.018	-10000	0	-10000	0	0
IL12RB1	-0.045	0.16	-10000	0	-0.59	36	36
GADD45B	-0.36	0.39	-10000	0	-0.81	148	148
IL12RB2	-0.13	0.24	-10000	0	-0.56	113	113
GADD45G	-0.38	0.41	-10000	0	-0.93	114	114
natural killer cell activation	-0.017	0.023	-10000	0	-10000	0	0
RELB	0.009	0.055	-10000	0	-0.52	5	5
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.033	0.16	-10000	0	-0.56	36	36
IL2RA	-0.065	0.18	-10000	0	-0.51	65	65
IFNG	-0.001	0.047	-10000	0	-0.5	4	4
STAT3 (dimer)	-0.37	0.36	-10000	0	-0.74	187	187
HLA-DRB5	-0.13	0.24	-10000	0	-0.55	115	115
FASLG	-0.46	0.47	-10000	0	-0.94	187	187
NF kappa B2 p52/RelB	-0.47	0.43	-10000	0	-0.87	210	210
CD4	0.004	0.066	-10000	0	-0.53	7	7
SOCS1	-0.032	0.15	-10000	0	-0.52	40	40
EntrezGene:6955	-0.002	0.009	-10000	0	-10000	0	0
CD3D	-0.12	0.23	-10000	0	-0.54	108	108
CD3E	-0.14	0.25	-10000	0	-0.55	127	127
CD3G	-0.031	0.14	-10000	0	-0.5	35	35
IL12Rbeta2/JAK2	-0.1	0.18	-10000	0	-0.41	113	113
CCL3	-0.57	0.58	-10000	0	-1.2	197	197
CCL4	-0.57	0.59	-10000	0	-1.2	198	198
HLA-A	0.004	0.071	-10000	0	-0.5	9	9
IL18/IL18R	-0.097	0.23	-10000	0	-0.43	131	131
NOS2	-0.43	0.45	-10000	0	-0.93	162	162
IL12/IL12R/TYK2/JAK2/SPHK2	-0.11	0.15	-10000	0	-0.41	51	51
IL1R1	-0.47	0.49	-10000	0	-1	172	172
IL4	0.019	0.023	-10000	0	-10000	0	0
JAK2	0.001	0.018	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.13	0.25	-10000	0	-0.57	87	87
RAB7A	-0.29	0.32	-10000	0	-0.71	111	111
lysosomal transport	-0.28	0.3	-10000	0	-0.67	114	114
FOS	-0.36	0.45	-10000	0	-0.91	143	143
STAT4 (dimer)	-0.43	0.41	-10000	0	-0.86	184	184
STAT5A (dimer)	-0.48	0.44	-10000	0	-0.88	212	212
GZMA	-0.53	0.54	-10000	0	-1.1	190	190
GZMB	-0.52	0.53	-10000	0	-1.1	189	189
HLX	-0.002	0.093	-10000	0	-0.53	14	14
LCK	-0.53	0.53	-10000	0	-1	215	215
TCR/CD3/MHC II/CD4	-0.17	0.25	-10000	0	-0.51	131	131
IL2/IL2R	-0.13	0.21	-10000	0	-0.47	101	101
MAPK14	-0.36	0.39	-10000	0	-0.81	155	155
CCR5	-0.42	0.45	-10000	0	-1	121	121
IL1B	-0.19	0.28	-10000	0	-0.57	157	157
STAT6	-0.11	0.12	-10000	0	-0.36	2	2
STAT4	-0.16	0.26	-10000	0	-0.54	148	148
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.002	0.09	-10000	0	-0.5	15	15
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.011	0.047	-10000	0	-0.57	3	3
IL12B	-0.015	0.054	-10000	0	-0.54	4	4
CD8A	-0.079	0.21	-10000	0	-0.56	76	76
CD8B	-0.035	0.16	-10000	0	-0.57	39	39
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.12	0.16	0.39	80	-10000	0	80
IL2RB	-0.099	0.22	-10000	0	-0.54	94	94
proteasomal ubiquitin-dependent protein catabolic process	-0.39	0.36	-10000	0	-0.77	184	184
IL2RG	-0.043	0.17	-10000	0	-0.53	49	49
IL12	-0.032	0.11	-10000	0	-0.46	27	27
STAT5A	0	0.093	-10000	0	-0.6	11	11
CD247	-0.02	0.13	-10000	0	-0.53	28	28
IL2	0.001	0.003	-10000	0	-10000	0	0
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.03	0.14	-10000	0	-0.62	23	23
IL12/IL12R/TYK2/JAK2	-0.53	0.57	-10000	0	-1	211	211
MAP2K3	-0.37	0.4	-10000	0	-0.81	158	158
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.37	0.4	-10000	0	-0.81	162	162
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.097	0.22	-10000	0	-0.55	91	91
IL18RAP	-0.086	0.22	-10000	0	-0.56	78	78
IL12Rbeta1/TYK2	-0.035	0.12	-10000	0	-0.44	36	36
EOMES	-0.01	0.16	-10000	0	-0.46	31	31
STAT1 (dimer)	-0.37	0.35	-10000	0	-0.74	180	180
T cell proliferation	-0.32	0.29	-10000	0	-0.63	170	170
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.058	0.19	-10000	0	-0.56	57	57
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.37	0.29	-10000	0	-0.69	173	173
ATF2	-0.34	0.36	-10000	0	-0.76	142	142

×

Aurora B signaling

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
Condensin I complex	-0.13	0.26	-9999	-0.55	114	114
STMN1	-0.11	0.2	-9999	-0.41	147	147
Aurora B/RasGAP/Survivin	-0.18	0.29	-9999	-0.58	150	150
Chromosomal passenger complex/Cul3 protein complex	-0.097	0.2	-9999	-0.43	104	104
BIRC5	-0.15	0.27	-9999	-0.58	127	127
DES	-0.35	0.47	-9999	-0.95	151	151
Aurora C/Aurora B/INCENP	-0.11	0.17	-9999	-0.34	145	145
Aurora B/TACC1	-0.1	0.17	-9999	-0.34	146	146
Aurora B/PP2A	-0.12	0.2	-9999	-0.4	146	146
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.031	0.076	-9999	-0.17	88	88
mitotic metaphase/anaphase transition	0	0.006	-9999	-10000	0	0
NDC80	-0.2	0.32	-9999	-0.61	167	167
Cul3 protein complex	-0.009	0.056	-9999	-0.37	11	11
KIF2C	-0.14	0.29	-9999	-0.47	149	149
PEBP1	0.007	0.042	-9999	-0.62	2	2
KIF20A	-0.18	0.27	-9999	-0.56	154	154
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.12	0.2	-9999	-0.4	146	146
SEPT1	0.009	0.055	-9999	-0.52	5	5
SMC2	0.014	0	-9999	-10000	0	0
SMC4	-0.015	0.12	-9999	-0.5	27	27
NSUN2/NPM1/Nucleolin	-0.17	0.34	-9999	-0.84	87	87
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.081	0.16	-9999	-0.3	146	146
AURKB	-0.17	0.28	-9999	-0.58	146	146
AURKC	-0.02	0.13	-9999	-0.52	30	30
CDCA8	-0.058	0.18	-9999	-0.54	58	58
cytokinesis	-0.28	0.41	-9999	-0.82	152	152
Aurora B/Septin1	-0.26	0.39	-9999	-0.78	150	150
AURKA	-0.015	0.12	-9999	-0.5	26	26
INCENP	0.009	0.009	-9999	-10000	0	0
KLHL13	0.012	0.041	-9999	-0.61	2	2
BUB1	-0.12	0.24	-9999	-0.56	108	108
hSgo1/Aurora B/Survivin	-0.24	0.36	-9999	-0.7	162	162
EVI5	0.013	0.003	-9999	-10000	0	0
RhoA/GTP	-0.25	0.36	-9999	-0.74	148	148
SGOL1	-0.12	0.24	-9999	-0.55	114	114
CENPA	-0.18	0.32	-9999	-0.57	154	154
NCAPG	-0.14	0.26	-9999	-0.56	128	128
Aurora B/HC8 Proteasome	-0.12	0.2	-9999	-0.4	146	146
NCAPD2	0.01	0.047	-9999	-0.5	4	4
Aurora B/PP1-gamma	-0.12	0.2	-9999	-0.4	146	146
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	-0.066	0.2	-9999	-0.55	66	66
NPM1	-0.14	0.24	-9999	-0.62	87	87
RASA1	0.014	0	-9999	-10000	0	0
KLHL9	0.002	0.086	-9999	-0.61	9	9
mitotic prometaphase	-0.006	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.12	0.2	-9999	-0.4	146	146
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.28	0.41	-9999	-0.8	154	154
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.14	0.24	-9999	-0.62	87	87
MYLK	-0.089	0.16	-9999	-0.3	155	155
KIF23	-0.12	0.24	-9999	-0.56	107	107
VIM	-0.17	0.24	-9999	-0.45	196	196
RACGAP1	0.003	0.061	-9999	-0.52	6	6
mitosis	0	0	-9999	-10000	0	0
NCL	-0.14	0.24	-9999	-0.62	87	87
Chromosomal passenger complex	-0.22	0.39	-9999	-0.7	153	153
Chromosomal passenger complex/EVI5	-0.18	0.32	-9999	-0.64	136	136
TACC1	0.014	0	-9999	-10000	0	0
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.014	0.1	-10000	0	-0.58	11	11
NFATC2	-0.13	0.31	-10000	0	-0.74	71	71
NFATC3	-0.048	0.11	-10000	0	-0.31	10	10
CD40LG	-0.38	0.48	-10000	0	-1	142	142
ITCH	-0.03	0.12	-10000	0	-0.53	3	3
CBLB	-0.031	0.13	-10000	0	-0.61	4	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.34	0.4	-10000	0	-0.94	102	102
JUNB	-0.036	0.16	-10000	0	-0.52	43	43
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.084	0.13	-10000	0	-0.3	82	82
T cell anergy	-0.094	0.2	-10000	0	-0.44	85	85
TLE4	-0.082	0.26	-10000	0	-0.68	51	51
Jun/NFAT1-c-4/p21SNFT	-0.35	0.44	-10000	0	-0.98	120	120
AP-1/NFAT1-c-4	-0.46	0.57	-10000	0	-1.2	139	139
IKZF1	-0.094	0.28	-10000	0	-0.76	52	52
T-helper 2 cell differentiation	-0.18	0.29	-10000	0	-0.75	65	65
AP-1/NFAT1	-0.17	0.26	-10000	0	-0.56	113	113
CALM1	-0.025	0.09	-10000	0	-0.7	2	2
EGR2	-0.29	0.53	-10000	0	-1.2	80	80
EGR3	-0.33	0.58	-10000	0	-1.2	113	113
NFAT1/FOXP3	-0.12	0.26	-10000	0	-0.68	59	59
EGR1	-0.11	0.23	-10000	0	-0.55	99	99
JUN	-0.004	0.079	-10000	0	-0.52	10	10
EGR4	-0.2	0.28	-10000	0	-0.56	172	172
mol:Ca2+	-0.04	0.084	-10000	0	-0.3	1	1
GBP3	-0.16	0.36	-10000	0	-0.83	88	88
FOSL1	-0.095	0.22	-10000	0	-0.54	91	91
NFAT1-c-4/MAF/IRF4	-0.32	0.43	-10000	0	-0.96	116	116
DGKA	-0.074	0.23	-10000	0	-0.67	39	39
CREM	0.012	0.037	-10000	0	-0.55	2	2
NFAT1-c-4/PPARG	-0.33	0.44	-10000	0	-0.97	119	119
CTLA4	-0.12	0.3	-10000	0	-0.7	79	79
NFAT1-c-4 (dimer)/EGR1	-0.38	0.51	-10000	0	-1	139	139
NFAT1-c-4 (dimer)/EGR4	-0.43	0.48	-10000	0	-1	145	145
FOS	-0.1	0.23	-10000	0	-0.57	87	87
IFNG	-0.17	0.24	-10000	0	-0.75	41	41
T cell activation	-0.17	0.28	-10000	0	-0.73	53	53
MAF	0.01	0.05	-10000	0	-0.61	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.22	0.4	0.83	99	-10000	0	99
TNF	-0.48	0.5	-10000	0	-1	178	178
FASLG	-0.34	0.55	-10000	0	-1.2	107	107
TBX21	-0.046	0.18	-10000	0	-0.54	51	51
BATF3	-0.036	0.16	-10000	0	-0.54	42	42
PRKCQ	-0.01	0.12	-10000	0	-0.59	18	18
PTPN1	-0.074	0.23	-10000	0	-0.64	44	44
NFAT1-c-4/ICER1	-0.32	0.44	-10000	0	-0.97	113	113
GATA3	-0.11	0.23	-10000	0	-0.54	100	100
T-helper 1 cell differentiation	-0.16	0.24	-10000	0	-0.73	42	42
IL2RA	-0.3	0.34	-10000	0	-0.82	98	98
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.075	0.23	-10000	0	-0.66	40	40
E2F1	-0.011	0.13	-10000	0	-0.52	26	26
PPARG	-0.014	0.13	-10000	0	-0.58	22	22
SLC3A2	-0.074	0.23	-10000	0	-0.65	42	42
IRF4	-0.048	0.18	-10000	0	-0.55	51	51
PTGS2	-0.41	0.52	-10000	0	-1.1	145	145
CSF2	-0.37	0.47	-10000	0	-1	131	131
JunB/Fra1/NFAT1-c-4	-0.37	0.46	-10000	0	-0.96	134	134
IL4	-0.19	0.31	-10000	0	-0.81	61	61
IL5	-0.37	0.47	-10000	0	-1	134	134
IL2	-0.17	0.29	-10000	0	-0.76	49	49
IL3	-0.066	0.072	-10000	0	-0.96	1	1
RNF128	-0.15	0.3	-10000	0	-0.56	150	150
NFATC1	-0.22	0.41	-10000	0	-0.84	99	99
CDK4	0.13	0.24	0.64	27	-0.6	1	28
PTPRK	-0.075	0.24	-10000	0	-0.66	42	42
IL8	-0.44	0.52	-10000	0	-1.1	157	157
POU2F1	0.013	0.029	-10000	0	-0.61	1	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.052	0.14	-9999	-0.37	78	78
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.091	0.17	-9999	-0.41	103	103
STXBP1	-0.014	0.12	-9999	-0.5	25	25
ACh/CHRNA1	-0.13	0.17	-9999	-0.38	144	144
RAB3GAP2/RIMS1/UNC13B	-0.075	0.14	-9999	-0.34	103	103
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	-0.11	0.24	-9999	-0.56	103	103
mol:ACh	-0.038	0.069	-9999	-0.14	147	147
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.14	0.21	-9999	-0.46	113	113
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.13	0.17	-9999	-0.38	144	144
UNC13B	0.013	0.029	-9999	-0.61	1	1
CHRNA1	-0.16	0.26	-9999	-0.54	143	143
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.16	0.21	-9999	-0.42	179	179
SNAP25	-0.075	0.13	-9999	-0.25	149	149
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.2	0.28	-9999	-0.55	179	179
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.05	0.16	-9999	-0.38	80	80
STX1A/SNAP25 fragment 1/VAMP2	-0.14	0.21	-9999	-0.46	113	113

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.081	-9999	-0.61	8	8
CCL5	-0.093	0.22	-9999	-0.55	89	89
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.14	0.19	-9999	-0.42	101	101
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.12	0.18	-9999	-0.46	74	74
Syndecan-1/Syntenin	-0.12	0.18	-9999	-0.45	72	72
MAPK3	-0.098	0.17	-9999	-0.48	41	41
HGF/MET	-0.17	0.23	-9999	-0.44	177	177
TGFB1/TGF beta receptor Type II	0.004	0.081	-9999	-0.61	8	8
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.12	0.18	-9999	-0.45	74	74
Syndecan-1/RANTES	-0.18	0.22	-9999	-0.47	131	131
Syndecan-1/CD147	-0.11	0.18	-9999	-0.43	72	72
Syndecan-1/Syntenin/PIP2	-0.13	0.17	-9999	-0.44	72	72
LAMA5	0.012	0.037	-9999	-0.55	2	2
positive regulation of cell-cell adhesion	-0.14	0.16	-9999	-0.43	72	72
MMP7	-0.15	0.26	-9999	-0.55	136	136
HGF	-0.078	0.2	-9999	-0.52	80	80
Syndecan-1/CASK	-0.13	0.18	-9999	-0.4	100	100
Syndecan-1/HGF/MET	-0.23	0.25	-9999	-0.52	162	162
regulation of cell adhesion	-0.088	0.16	-9999	-0.46	41	41
HPSE	-0.057	0.19	-9999	-0.57	56	56
positive regulation of cell migration	-0.14	0.19	-9999	-0.42	101	101
SDC1	-0.14	0.19	-9999	-0.42	101	101
Syndecan-1/Collagen	-0.14	0.19	-9999	-0.42	101	101
PPIB	0.014	0	-9999	-10000	0	0
MET	-0.14	0.25	-9999	-0.55	129	129
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.15	0.25	-9999	-0.53	136	136
MAPK1	-0.098	0.17	-9999	-0.48	41	41
homophilic cell adhesion	-0.14	0.19	-9999	-0.41	101	101
MMP1	-0.048	0.16	-9999	-0.5	51	51

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.084	0.15	-9999	-0.34	115	115
E-cadherin/beta catenin	-0.092	0.17	-9999	-0.39	109	109
CTNNB1	0.014	0	-9999	-10000	0	0
JUP	0.001	0.087	-9999	-0.58	10	10
CDH1	-0.12	0.24	-9999	-0.55	109	109

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.14	0.19	-10000	0	-0.46	99	99
FYN	-0.15	0.27	-10000	0	-0.54	122	122
LAT/GRAP2/SLP76	-0.18	0.22	-10000	0	-0.5	118	118
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.11	0.19	-10000	0	-0.39	116	116
B2M	0.006	0.054	-10000	0	-0.51	5	5
IKBKG	-0.036	0.046	-10000	0	-0.14	26	26
MAP3K8	-0.006	0.1	-10000	0	-0.51	18	18
mol:Ca2+	-0.027	0.043	-10000	0	-0.11	91	91
integrin-mediated signaling pathway	-0.011	0.06	-10000	0	-0.34	15	15
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.16	0.27	-10000	0	-0.55	122	122
TRPV6	-0.12	0.24	-10000	0	-0.57	99	99
CD28	-0.079	0.21	-10000	0	-0.55	75	75
SHC1	-0.15	0.27	-10000	0	-0.54	118	118
receptor internalization	-0.13	0.24	-10000	0	-0.5	107	107
PRF1	-0.18	0.37	-10000	0	-0.97	68	68
KRAS	0.013	0.024	-10000	0	-0.5	1	1
GRB2	0.013	0.024	-10000	0	-0.5	1	1
COT/AKT1	-0.087	0.16	-10000	0	-0.34	97	97
LAT	-0.17	0.27	-10000	0	-0.54	127	127
EntrezGene:6955	-0.002	0.006	-10000	0	-10000	0	0
CD3D	-0.12	0.23	-10000	0	-0.54	108	108
CD3E	-0.14	0.25	-10000	0	-0.55	127	127
CD3G	-0.031	0.14	-10000	0	-0.5	35	35
RASGRP2	-0.007	0.025	-10000	0	-0.19	2	2
RASGRP1	-0.12	0.2	-10000	0	-0.4	120	120
HLA-A	0.001	0.071	-10000	0	-0.5	9	9
RASSF5	-0.004	0.1	-10000	0	-0.56	15	15
RAP1A/GTP/RAPL	-0.011	0.06	-10000	0	-0.34	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.018	0.063	-10000	0	-0.12	50	50
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.066	0.081	-10000	0	-0.22	65	65
PRKCA	-0.083	0.11	-10000	0	-0.25	91	91
GRAP2	-0.051	0.18	-10000	0	-0.54	54	54
mol:IP3	-0.11	0.19	0.2	55	-0.39	107	162
EntrezGene:6957	-0.002	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.12	0.22	-10000	0	-0.46	106	106
ORAI1	0.072	0.13	0.31	98	-10000	0	98
CSK	-0.16	0.27	-10000	0	-0.55	119	119
B7 family/CD28	-0.22	0.28	-10000	0	-0.61	123	123
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.18	0.3	-10000	0	-0.59	128	128
PTPN6	-0.16	0.28	-10000	0	-0.56	124	124
VAV1	-0.17	0.28	-10000	0	-0.56	123	123
Monovalent TCR/CD3	-0.12	0.2	-10000	0	-0.37	156	156
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.18	0.3	-10000	0	-0.56	141	141
PAG1	-0.16	0.27	-10000	0	-0.55	119	119
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.18	0.3	-10000	0	-0.6	123	123
CD80	-0.047	0.17	-10000	0	-0.52	51	51
CD86	-0.027	0.15	-10000	0	-0.57	32	32
PDK1/CARD11/BCL10/MALT1	-0.081	0.099	-10000	0	-0.26	74	74
HRAS	0.014	0	-10000	0	-10000	0	0
GO:0035030	-0.16	0.25	-10000	0	-0.52	118	118
CD8A	-0.081	0.21	-10000	0	-0.56	76	76
CD8B	-0.038	0.16	-10000	0	-0.58	39	39
PTPRC	-0.044	0.17	-10000	0	-0.55	47	47
PDK1/PKC theta	-0.13	0.23	-10000	0	-0.48	113	113
CSK/PAG1	-0.15	0.26	-10000	0	-0.54	112	112
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.003	0.073	-10000	0	-0.44	11	11
GRAP2/SLP76	-0.19	0.26	-10000	0	-0.56	125	125
STIM1	0.039	0.063	-10000	0	-10000	0	0
RAS family/GTP	-0.025	0.084	-10000	0	-0.17	30	30
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.14	0.26	-10000	0	-0.53	107	107
mol:DAG	-0.12	0.16	-10000	0	-0.35	113	113
RAP1A/GDP	-0.006	0.027	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.02	0.13	-10000	0	-0.53	28	28
cytotoxic T cell degranulation	-0.17	0.35	-10000	0	-0.88	72	72
RAP1A/GTP	-0.004	0.006	-10000	0	-0.067	2	2
mol:PI-3-4-5-P3	-0.14	0.22	-10000	0	-0.45	120	120
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.15	0.24	0.23	40	-0.5	109	149
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.053	0.18	-10000	0	-0.54	56	56
GRB2/SOS1	-0.001	0.016	-10000	0	-0.35	1	1
LAT/GRAP2/SLP76/VAV1	-0.17	0.22	-10000	0	-0.49	121	121
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.029	-10000	0	-0.61	1	1
CD8 heterodimer	-0.086	0.21	-10000	0	-0.47	98	98
CARD11	-0.01	0.12	-10000	0	-0.58	19	19
PRKCB	-0.11	0.12	-10000	0	-0.27	118	118
PRKCE	-0.086	0.11	-10000	0	-0.26	91	91
PRKCQ	-0.16	0.26	-10000	0	-0.53	120	120
LCP2	-0.003	0.094	-10000	0	-0.5	16	16
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.092	0.16	-10000	0	-0.33	114	114
IKK complex	-0.012	0.062	-10000	0	-0.11	26	26
RAS family/GDP	-0.007	0.009	-10000	0	-10000	0	0
MAP3K14	-0.058	0.13	-10000	0	-0.27	71	71
PDPK1	-0.1	0.18	-10000	0	-0.37	109	109
TCR/CD3/MHC I/CD8/Fyn	-0.18	0.31	-10000	0	-0.61	131	131

×

IL4-mediated signaling events

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
BCL2L1	-0.4	0.44	-10000	0	-1.1	81	81
STAT6 (cleaved dimer)	-0.48	0.44	-10000	0	-0.99	161	161
IGHG1	-0.16	0.21	-10000	0	-0.57	37	37
IGHG3	-0.39	0.42	-10000	0	-0.94	129	129
AKT1	-0.24	0.29	-10000	0	-0.74	71	71
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.3	-10000	0	-0.78	67	67
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.27	-10000	0	-0.69	60	60
THY1	-0.41	0.46	-10000	0	-1.1	98	98
MYB	-0.062	0.19	-10000	0	-0.55	62	62
HMGA1	0.011	0.044	-10000	0	-0.53	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.33	0.35	-10000	0	-0.76	134	134
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.27	-10000	0	-0.68	63	63
SP1	0.021	0.01	-10000	0	-10000	0	0
INPP5D	0.008	0.058	-10000	0	-0.54	5	5
SOCS5	0.028	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.46	0.46	-10000	0	-1	146	146
SOCS1	-0.3	0.33	-10000	0	-0.76	109	109
SOCS3	-0.36	0.42	-10000	0	-0.94	124	124
FCER2	-0.43	0.45	-10000	0	-1.1	106	106
PARP14	-0.002	0.087	-10000	0	-0.53	12	12
CCL17	-0.41	0.45	-10000	0	-1.1	102	102
GRB2	0.013	0.024	-10000	0	-0.5	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.23	-10000	0	-0.62	52	52
T cell proliferation	-0.41	0.46	-10000	0	-1.1	111	111
IL4R/JAK1	-0.4	0.44	-10000	0	-1.1	97	97
EGR2	-0.51	0.54	-10000	0	-1.3	116	116
JAK2	-0.003	0.027	-10000	0	-10000	0	0
JAK3	-0.06	0.19	-10000	0	-0.54	62	62
PIK3R1	0.014	0	-10000	0	-10000	0	0
JAK1	0.005	0.012	-10000	0	-10000	0	0
COL1A2	-0.16	0.25	-10000	0	-0.73	44	44
CCL26	-0.41	0.45	-10000	0	-1.1	88	88
IL4R	-0.42	0.47	-10000	0	-1.1	93	93
PTPN6	0.007	0.098	-10000	0	-0.54	14	14
IL13RA2	-0.61	0.59	-10000	0	-1.2	183	183
IL13RA1	-0.012	0.077	-10000	0	-0.64	6	6
IRF4	-0.19	0.35	-10000	0	-1.1	45	45
ARG1	-0.13	0.24	-10000	0	-0.81	29	29
CBL	-0.3	0.33	-10000	0	-0.74	123	123
GTF3A	0.009	0.034	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.012	0.066	-10000	0	-0.47	6	6
IRF4/BCL6	-0.16	0.32	-10000	0	-1	43	43
CD40LG	-0.038	0.15	-10000	0	-0.5	44	44
MAPK14	-0.33	0.36	-10000	0	-0.8	127	127
mitosis	-0.23	0.28	-10000	0	-0.7	71	71
STAT6	-0.45	0.51	-10000	0	-1.1	119	119
SPI1	-0.004	0.11	-10000	0	-0.55	17	17
RPS6KB1	-0.22	0.27	-10000	0	-0.68	65	65
STAT6 (dimer)	-0.45	0.51	-10000	0	-1.1	119	119
STAT6 (dimer)/PARP14	-0.44	0.48	-10000	0	-1.1	124	124
mast cell activation	0.011	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.28	0.32	-10000	0	-0.8	82	82
FRAP1	-0.24	0.29	-10000	0	-0.74	71	71
LTA	-0.43	0.49	-10000	0	-1.2	95	95
FES	0.01	0.05	-10000	0	-0.52	4	4
T-helper 1 cell differentiation	0.44	0.5	1.1	119	-10000	0	119
CCL11	-0.39	0.42	-10000	0	-1	88	88
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.25	0.31	-10000	0	-0.79	70	70
IL2RG	-0.044	0.17	-10000	0	-0.53	49	49
IL10	-0.5	0.57	-10000	0	-1.2	136	136
IRS1	0.013	0.029	-10000	0	-0.61	1	1
IRS2	0.013	0.029	-10000	0	-0.61	1	1
IL4	-0.097	0.12	-10000	0	-10000	0	0
IL5	-0.4	0.44	-10000	0	-1.1	84	84
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.33	0.36	-10000	0	-0.83	94	94
COL1A1	-0.36	0.51	-10000	0	-1.1	112	112
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.4	0.45	-10000	0	-1.1	82	82
IL2R gamma/JAK3	-0.077	0.2	-10000	0	-0.45	93	93
TFF3	-0.42	0.46	-10000	0	-1.1	104	104
ALOX15	-0.41	0.45	-10000	0	-1.1	84	84
MYBL1	0.01	0.047	-10000	0	-0.5	4	4
T-helper 2 cell differentiation	-0.36	0.38	-10000	0	-0.86	120	120
SHC1	0.009	0.053	-10000	0	-0.5	5	5
CEBPB	-0.003	0.11	-10000	0	-0.58	15	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.26	-10000	0	-0.67	59	59
mol:PI-3-4-5-P3	-0.24	0.3	-10000	0	-0.74	71	71
PI3K	-0.26	0.31	-10000	0	-0.8	71	71
DOK2	-0.074	0.2	-10000	0	-0.54	74	74
ETS1	0.017	0.073	-10000	0	-0.52	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.22	-10000	0	-0.6	50	50
ITGB3	-0.44	0.5	-10000	0	-1.2	106	106
PIGR	-0.51	0.57	-10000	0	-1.3	120	120
IGHE	0.021	0.063	-10000	0	-0.26	11	11
MAPKKK cascade	-0.17	0.22	-10000	0	-0.59	50	50
BCL6	0.016	0.006	-10000	0	-10000	0	0
OPRM1	-0.42	0.45	-10000	0	-1.1	107	107
RETNLB	-0.4	0.44	-10000	0	-1.1	88	88
SELP	-0.41	0.45	-10000	0	-1.1	88	88
AICDA	-0.39	0.43	-10000	0	-1.1	84	84

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.097	0.29	-10000	0	-0.72	56	56
IHH	-0.011	0.081	-10000	0	-0.52	6	6
SHH Np/Cholesterol/GAS1	-0.091	0.16	-10000	0	-0.32	131	131
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.09	0.15	0.32	131	-10000	0	131
SMO/beta Arrestin2	-0.033	0.18	-10000	0	-0.74	14	14
SMO	-0.043	0.19	-10000	0	-0.73	17	17
AKT1	0.005	0.082	-10000	0	-0.32	2	2
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	0.007	0.066	-10000	0	-0.57	6	6
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.042	0.18	-10000	0	-0.71	17	17
STIL	-0.092	0.22	-10000	0	-0.55	63	63
DHH N/PTCH2	-0.062	0.15	-10000	0	-0.41	70	70
DHH N/PTCH1	-0.068	0.2	-10000	0	-0.62	26	26
PIK3CA	0.014	0	-10000	0	-10000	0	0
DHH	-0.05	0.18	-10000	0	-0.56	52	52
PTHLH	-0.11	0.34	-10000	0	-0.94	54	54
determination of left/right symmetry	-0.042	0.18	-10000	0	-0.71	17	17
PIK3R1	0.014	0	-10000	0	-10000	0	0
skeletal system development	-0.11	0.34	-10000	0	-0.92	54	54
IHH N/Hhip	-0.12	0.21	-10000	0	-0.45	128	128
DHH N/Hhip	-0.15	0.22	-10000	0	-0.44	160	160
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.042	0.18	-10000	0	-0.71	17	17
pancreas development	-0.14	0.26	-10000	0	-0.56	125	125
HHAT	-0.006	0.11	-10000	0	-0.59	16	16
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.017	0.12	-10000	0	-0.5	28	28
somite specification	-0.042	0.18	-10000	0	-0.71	17	17
SHH Np/Cholesterol/PTCH1	-0.093	0.22	-10000	0	-0.56	53	53
SHH Np/Cholesterol/PTCH2	-0.088	0.15	-10000	0	-0.32	129	129
SHH Np/Cholesterol/Megalin	-0.18	0.21	-10000	0	-0.37	232	232
SHH	-0.082	0.19	-10000	0	-0.42	111	111
catabolic process	-0.043	0.18	-10000	0	-0.63	21	21
SMO/Vitamin D3	-0.083	0.22	-10000	0	-0.6	44	44
SHH Np/Cholesterol/Hhip	-0.16	0.21	-10000	0	-0.36	199	199
LRP2	-0.19	0.28	-10000	0	-0.56	166	166
receptor-mediated endocytosis	-0.18	0.22	-10000	0	-0.59	75	75
SHH Np/Cholesterol/BOC	-0.079	0.15	-10000	0	-0.32	114	114
SHH Np/Cholesterol/CDO	-0.094	0.16	-10000	0	-0.33	132	132
mesenchymal cell differentiation	0.16	0.21	0.36	199	-10000	0	199
mol:Vitamin D3	-0.09	0.22	-10000	0	-0.57	52	52
IHH N/PTCH2	-0.011	0.11	-10000	0	-0.46	23	23
CDON	-0.021	0.14	-10000	0	-0.57	28	28
IHH N/PTCH1	-0.043	0.19	-10000	0	-0.64	21	21
Megalin/LRPAP1	-0.14	0.19	-10000	0	-0.4	166	166
PTCH2	-0.011	0.12	-10000	0	-0.57	20	20
SHH Np/Cholesterol	-0.077	0.14	-10000	0	-0.32	111	111
PTCH1	-0.043	0.19	-10000	0	-0.63	21	21
HHIP	-0.14	0.26	-10000	0	-0.56	125	125

×

Glypican 2 network

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
MDK	-0.048	0.18	-9999	-0.55	51	51
GPC2	-0.018	0.14	-9999	-0.58	25	25
GPC2/Midkine	-0.065	0.16	-9999	-0.42	71	71
neuron projection morphogenesis	-0.065	0.16	-9999	-0.42	71	71

×

Syndecan-4-mediated 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
PTK2	-0.001	0.056	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.24	-9999	-0.56	92	92
positive regulation of JNK cascade	-0.15	0.22	-9999	-0.52	100	100
Syndecan-4/ADAM12	-0.18	0.27	-9999	-0.58	111	111
CCL5	-0.093	0.22	-9999	-0.55	89	89
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.013	0.12	-9999	-0.51	24	24
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0.001	0.04	-9999	-0.48	3	3
ADAM12	-0.078	0.2	-9999	-0.52	81	81
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.031	0.043	-9999	-0.18	1	1
Syndecan-4/Laminin alpha1	-0.17	0.27	-9999	-0.6	104	104
Syndecan-4/CXCL12/CXCR4	-0.14	0.25	-9999	-0.55	100	100
Syndecan-4/Laminin alpha3	-0.16	0.26	-9999	-0.59	100	100
MDK	-0.048	0.18	-9999	-0.55	51	51
Syndecan-4/FZD7	-0.16	0.28	-9999	-0.61	102	102
Syndecan-4/Midkine	-0.16	0.26	-9999	-0.59	99	99
FZD7	-0.047	0.18	-9999	-0.59	47	47
Syndecan-4/FGFR1/FGF	-0.15	0.21	-9999	-0.52	93	93
THBS1	-0.092	0.22	-9999	-0.53	91	91
integrin-mediated signaling pathway	-0.16	0.26	-9999	-0.58	103	103
positive regulation of MAPKKK cascade	-0.15	0.22	-9999	-0.52	100	100
Syndecan-4/TACI	-0.14	0.24	-9999	-0.57	93	93
CXCR4	-0.013	0.12	-9999	-0.54	23	23
cell adhesion	0.02	0.055	-9999	-0.26	11	11
Syndecan-4/Dynamin	-0.13	0.24	-9999	-0.56	92	92
Syndecan-4/TSP1	-0.18	0.26	-9999	-0.58	112	112
Syndecan-4/GIPC	-0.14	0.24	-9999	-0.56	92	92
Syndecan-4/RANTES	-0.19	0.26	-9999	-0.6	105	105
ITGB1	0.012	0.033	-9999	-0.5	2	2
LAMA1	-0.058	0.2	-9999	-0.58	56	56
LAMA3	-0.041	0.17	-9999	-0.56	45	45
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.038	0.054	-9999	-0.55	1	1
Syndecan-4/alpha-Actinin	-0.15	0.26	-9999	-0.57	103	103
TFPI	-0.09	0.22	-9999	-0.54	88	88
F2	-0.008	0.066	-9999	-0.49	8	8
alpha5/beta1 Integrin	-0.02	0.085	-9999	-0.37	25	25
positive regulation of cell adhesion	-0.18	0.28	-9999	-0.6	116	116
ACTN1	-0.02	0.13	-9999	-0.5	31	31
TNC	-0.054	0.18	-9999	-0.55	56	56
Syndecan-4/CXCL12	-0.14	0.24	-9999	-0.56	95	95
FGF6	0.001	0.003	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	0.003	0.078	-9999	-0.55	9	9
TNFRSF13B	-0.004	0.069	-9999	-0.5	9	9
FGF2	0.011	0.047	-9999	-0.57	3	3
FGFR1	0.012	0.041	-9999	-0.61	2	2
Syndecan-4/PI-4-5-P2	-0.14	0.24	-9999	-0.57	92	92
mol:GDP	0	0	-9999	-10000	0	0
FN1	0	0.096	-9999	-0.49	17	17
cell migration	-0.007	0.018	-9999	-10000	0	0
PRKCD	-0.011	0.13	-9999	-0.58	22	22
vasculogenesis	-0.18	0.25	-9999	-0.56	112	112
SDC4	-0.15	0.26	-9999	-0.6	92	92
Syndecan-4/Tenascin C	-0.17	0.27	-9999	-0.61	103	103
Syndecan-4/PI-4-5-P2/PKC alpha	-0.025	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.24	-9999	-0.56	92	92
MMP9	-0.15	0.25	-9999	-0.53	136	136
Rac1/GTP	0.02	0.057	-9999	-0.27	11	11
cytoskeleton organization	-0.13	0.23	-9999	-0.54	92	92
GIPC1	0.013	0.024	-9999	-0.5	1	1
Syndecan-4/TFPI	-0.18	0.26	-9999	-0.6	98	98

×

Thromboxane A2 receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.008	0.047	-10000	0	-0.5	4	4
GNB1/GNG2	-0.081	0.081	-10000	0	-0.19	142	142
AKT1	-0.063	0.12	-10000	0	-0.23	34	34
EGF	-0.047	0.18	-10000	0	-0.56	49	49
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.016	0.073	-10000	0	-0.32	4	4
mol:Ca2+	-0.1	0.16	-10000	0	-0.3	141	141
LYN	0.013	0.084	-10000	0	-0.33	10	10
RhoA/GTP	-0.053	0.053	-10000	0	-0.15	3	3
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.12	0.18	-10000	0	-0.35	143	143
GNG2	0.009	0.058	-10000	0	-0.61	4	4
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.008	0.1	-10000	0	-0.38	23	23
G beta5/gamma2	-0.1	0.1	-10000	0	-0.24	113	113
PRKCH	-0.12	0.18	-10000	0	-0.34	132	132
DNM1	-0.11	0.23	-10000	0	-0.53	106	106
TXA2/TP beta/beta Arrestin3	-0.045	0.076	-10000	0	-0.25	31	31
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.043	0.16	-10000	0	-0.51	50	50
G12 family/GTP	-0.13	0.13	-10000	0	-0.3	141	141
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.009	0.055	-10000	0	-0.58	4	4
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.061	0.11	0.31	29	-10000	0	29
mol:NADP	0.002	0.081	-10000	0	-0.54	10	10
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.041	0.17	-10000	0	-0.59	42	42
mol:IP3	-0.13	0.19	-10000	0	-0.38	141	141
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.18	0.25	-10000	0	-0.51	141	141
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	-0.042	0.12	-10000	0	-0.34	18	18
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.007	0.093	-10000	0	-0.35	13	13
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.016	0.13	-10000	0	-0.53	26	26
PRKCB1	-0.13	0.19	-10000	0	-0.37	142	142
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.002	0.081	-10000	0	-0.54	10	10
TXA2/TXA2-R family	-0.19	0.26	-10000	0	-0.53	143	143
LCK	-0.029	0.12	-10000	0	-0.34	24	24
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.027	0.069	-10000	0	-0.33	9	9
TXA2-R family/G12 family/GDP/G beta/gamma	0.023	0.047	-10000	0	-0.76	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.025	0.066	-10000	0	-0.38	4	4
MAPK14	-0.074	0.13	-10000	0	-0.24	93	93
TGM2/GTP	-0.15	0.21	-10000	0	-0.42	143	143
MAPK11	-0.076	0.13	-10000	0	-0.24	136	136
ARHGEF1	-0.056	0.097	-10000	0	-0.2	18	18
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.14	0.2	-10000	0	-0.39	143	143
RAB11/GDP	0.015	0.001	-10000	0	-10000	0	0
ICAM1	-0.1	0.16	-10000	0	-0.3	149	149
cAMP biosynthetic process	-0.13	0.18	-10000	0	-0.35	145	145
Gq family/GTP/EBP50	0.006	0.085	-10000	0	-0.29	25	25
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.017	0.071	-10000	0	-0.32	4	4
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.026	0.11	-10000	0	-0.31	26	26
VCAM1	-0.13	0.19	-10000	0	-0.37	147	147
TP beta/Gq family/GDP/G beta5/gamma2	0.008	0.1	-10000	0	-0.38	23	23
platelet activation	-0.098	0.17	-10000	0	-0.3	141	141
PGI2/IP	-0.018	0.09	-10000	0	-0.39	26	26
PRKACA	-0.012	0.084	-10000	0	-0.3	18	18
Gq family/GDP/G beta5/gamma2	0.006	0.096	-10000	0	-0.35	24	24
TXA2/TP beta/beta Arrestin2	-0.069	0.15	-10000	0	-0.54	36	36
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.007	0.089	-10000	0	-0.3	24	24
mol:DAG	-0.15	0.21	-10000	0	-0.41	142	142
EGFR	-0.083	0.22	-10000	0	-0.56	79	79
TXA2/TP alpha	-0.18	0.24	-10000	0	-0.48	145	145
Gq family/GTP	-0.017	0.071	-10000	0	-0.24	38	38
YES1	0.016	0.075	-10000	0	-0.32	4	4
GNAI2/GTP	-0.025	0.064	-10000	0	-0.36	5	5
PGD2/DP	-0.037	0.12	-10000	0	-0.37	50	50
SLC9A3R1	0.01	0.05	-10000	0	-0.61	3	3
FYN	0.017	0.071	-10000	0	-0.32	4	4
mol:NO	0.002	0.081	-10000	0	-0.54	10	10
GNA15	-0.01	0.12	-10000	0	-0.58	19	19
PGK/cGMP	-0.04	0.12	-10000	0	-0.36	51	51
RhoA/GDP	0.015	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.027	0.076	-10000	0	-0.43	6	6
NOS3	0.002	0.081	-10000	0	-0.54	10	10
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.12	0.18	-10000	0	-0.34	133	133
PRKCB	-0.14	0.2	-10000	0	-0.38	152	152
PRKCE	-0.12	0.18	-10000	0	-0.35	134	134
PRKCD	-0.14	0.2	-10000	0	-0.39	142	142
PRKCG	-0.18	0.22	-10000	0	-0.43	164	164
muscle contraction	-0.18	0.25	-10000	0	-0.49	146	146
PRKCZ	-0.13	0.19	-10000	0	-0.35	151	151
ARR3	0.002	0.024	-10000	0	-0.5	1	1
TXA2/TP beta	-0.028	0.073	-10000	0	-0.4	5	5
PRKCQ	-0.12	0.18	-10000	0	-0.35	148	148
MAPKKK cascade	-0.16	0.23	-10000	0	-0.45	145	145
SELE	-0.13	0.18	-10000	0	-0.34	158	158
TP beta/GNAI2/GDP/G beta/gamma	-0.025	0.069	-10000	0	-0.38	5	5
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.018	0.13	-10000	0	-0.58	25	25
chemotaxis	-0.22	0.3	-10000	0	-0.61	144	144
GNA12	0.013	0.029	-10000	0	-0.61	1	1
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.005	0.076	-10000	0	-0.61	7	7
Rac1/GTP	0.003	0.005	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.038	0.051	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.092	0.14	-9999	-0.43	44	44
JUN	-0.079	0.2	-9999	-0.54	49	49
HRAS	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.16	0.22	-9999	-0.45	127	127
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.012	0.037	-9999	-0.55	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.16	0.22	-9999	-0.45	126	126
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.095	0.18	-9999	-0.37	120	120
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.21	-9999	-0.64	48	48
GRB7	-0.031	0.14	-9999	-0.5	38	38
RET51/GFRalpha1/GDNF	-0.16	0.22	-9999	-0.45	126	126
MAPKKK cascade	-0.13	0.18	-9999	-0.58	44	44
BCAR1	0.013	0.029	-9999	-0.61	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.091	0.17	-9999	-0.36	116	116
lamellipodium assembly	-0.086	0.13	-9999	-0.4	43	43
RET51/GFRalpha1/GDNF/SHC	-0.16	0.23	-9999	-0.46	126	126
PIK3CA	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.093	0.18	-9999	-0.37	116	116
RET9/GFRalpha1/GDNF/Shank3	-0.096	0.18	-9999	-0.36	122	122
MAPK3	-0.11	0.22	-9999	-0.6	48	48
DOK1	0.013	0.029	-9999	-0.61	1	1
DOK6	-0.048	0.18	-9999	-0.59	48	48
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.1	0.22	-9999	-0.57	58	58
DOK5	0.001	0.09	-9999	-0.61	10	10
GFRA1	-0.073	0.21	-9999	-0.57	69	69
MAPK8	-0.087	0.2	-9999	-0.56	48	48
HRAS/GTP	-0.14	0.21	-9999	-0.43	126	126
tube development	-0.089	0.16	-9999	-0.39	84	84
MAPK1	-0.11	0.22	-9999	-0.6	48	48
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.15	-9999	-0.32	83	83
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.006	0.066	-9999	-0.5	8	8
RET51/GFRalpha1/GDNF/Dok6	-0.18	0.26	-9999	-0.75	58	58
SHC1	0.009	0.053	-9999	-0.5	5	5
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.23	-9999	-0.46	135	135
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.23	-9999	-0.46	133	133
PRKCA	0.013	0.029	-9999	-0.61	1	1
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.069	0.18	-9999	-0.5	51	51
PIK3R1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.044	0.15	-9999	-0.34	83	83
RET51/GFRalpha1/GDNF/Grb7	-0.18	0.24	-9999	-0.49	128	128
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.24	-9999	-0.56	107	107
DOK4	-0.008	0.12	-9999	-0.61	17	17
JNK cascade	-0.077	0.19	-9999	-0.52	49	49
RET9/GFRalpha1/GDNF/FRS2	-0.092	0.17	-9999	-0.37	116	116
SHANK3	0.004	0.074	-9999	-0.52	9	9
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.029	-9999	-0.61	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.043	0.15	-9999	-0.33	83	83
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.094	0.21	-9999	-0.55	49	49
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.094	0.21	-9999	-0.37	126	126
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.098	0.22	-9999	-0.64	42	42
PI3K	-0.09	0.24	-9999	-0.58	58	58
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.089	0.16	-9999	-0.39	84	84
GRB10	0.012	0.037	-9999	-0.55	2	2
activation of MAPKK activity	-0.088	0.2	-9999	-0.48	71	71
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.45	126	126
GAB1	0.012	0.037	-9999	-0.55	2	2
IRS1	0.013	0.029	-9999	-0.61	1	1
IRS2	0.013	0.029	-9999	-0.61	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.099	0.22	-9999	-0.66	41	41
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.22	-9999	-0.45	126	126
GRB2	0.013	0.024	-9999	-0.5	1	1
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.07	0.21	-9999	-0.59	64	64
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.16	0.22	-9999	-0.45	126	126
Rac1/GTP	-0.1	0.16	-9999	-0.49	43	43
RET9/GFRalpha1/GDNF	-0.1	0.19	-9999	-0.41	115	115
GFRalpha1/GDNF	-0.12	0.22	-9999	-0.47	115	115

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.14	0.37	-9999	-1	57	57
MKNK1	0.009	0.057	-9999	-0.61	4	4
MAPK14	-0.038	0.12	-9999	-0.36	7	7
ATF2/c-Jun	-0.024	0.14	-9999	-0.56	16	16
MAPK11	-0.044	0.14	-9999	-0.31	73	73
MITF	-0.038	0.16	-9999	-0.35	75	75
MAPKAPK5	-0.036	0.15	-9999	-0.34	73	73
KRT8	-0.11	0.22	-9999	-0.42	118	118
MAPKAPK3	0.012	0.041	-9999	-0.61	2	2
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.059	0.19	-9999	-0.44	73	73
CEBPB	-0.049	0.18	-9999	-0.39	81	81
SLC9A1	-0.037	0.16	-9999	-0.36	73	73
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.039	0.17	-9999	-0.35	82	82
p38alpha-beta/MNK1	-0.036	0.16	-9999	-0.57	12	12
JUN	-0.024	0.14	-9999	-0.56	16	16
PPARGC1A	-0.054	0.19	-9999	-0.4	82	82
USF1	-0.036	0.15	-9999	-0.34	73	73
RAB5/GDP/GDI1	-0.05	0.092	-9999	-0.39	8	8
NOS2	-0.082	0.28	-9999	-1	26	26
DDIT3	-0.04	0.16	-9999	-0.35	74	74
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.037	0.15	-9999	-0.46	20	20
p38alpha-beta/HBP1	-0.033	0.15	-9999	-0.55	8	8
CREB1	-0.037	0.16	-9999	-0.37	71	71
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.025	0.14	-9999	-0.54	10	10
RPS6KA4	-0.036	0.15	-9999	-0.34	73	73
PLA2G4A	-0.043	0.17	-9999	-0.6	21	21
GDI1	-0.036	0.15	-9999	-0.34	73	73
TP53	-0.057	0.19	-9999	-0.43	80	80
RPS6KA5	-0.043	0.16	-9999	-0.36	80	80
ESR1	-0.052	0.17	-9999	-0.37	86	86
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.047	0.16	-9999	-0.36	80	80
MEF2A	-0.037	0.16	-9999	-0.35	73	73
EIF4EBP1	-0.04	0.16	-9999	-0.37	72	72
KRT19	-0.098	0.21	-9999	-0.4	119	119
ELK4	-0.036	0.15	-9999	-0.34	73	73
ATF6	-0.036	0.15	-9999	-0.34	73	73
ATF1	-0.037	0.16	-9999	-0.36	75	75
p38alpha-beta/MAPKAPK2	-0.033	0.15	-9999	-0.34	73	73
p38alpha-beta/MAPKAPK3	-0.035	0.16	-9999	-0.51	12	12

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0.033	-9999	-0.5	2	2
ITGB7	-0.034	0.16	-9999	-0.55	40	40
ITGA4	-0.056	0.19	-9999	-0.54	58	58
alpha4/beta7 Integrin	-0.081	0.18	-9999	-0.44	86	86
alpha4/beta1 Integrin	-0.05	0.13	-9999	-0.4	58	58

×

amb2 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.083	0.18	-9999	-0.49	65	65
alphaM/beta2 Integrin/GPIbA	-0.079	0.17	-9999	-0.47	66	66
alphaM/beta2 Integrin/proMMP-9	-0.16	0.22	-9999	-0.41	170	170
PLAUR	-0.024	0.14	-9999	-0.5	34	34
HMGB1	-0.001	0.022	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.067	0.16	-9999	-0.5	51	51
AGER	-0.026	0.12	-9999	-0.61	18	18
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	-0.019	0.14	-9999	-0.6	25	25
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.14	0.19	-9999	-0.58	48	48
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.15	0.25	-9999	-0.53	136	136
CYR61	-0.11	0.24	-9999	-0.56	99	99
TLN1	0.014	0	-9999	-10000	0	0
Rap1/GTP	-0.091	0.13	-9999	-0.42	41	41
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.03	0.14	-9999	-0.49	37	37
MYH2	-0.088	0.15	-9999	-0.42	40	40
MST1R	0.005	0.074	-9999	-0.59	7	7
leukocyte activation during inflammatory response	-0.12	0.19	-9999	-0.45	82	82
APOB	-0.076	0.21	-9999	-0.56	73	73
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.013	0.12	-9999	-0.54	23	23
JAM3	0.014	0	-9999	-10000	0	0
GP1BA	-0.005	0.11	-9999	-0.59	15	15
alphaM/beta2 Integrin/CTGF	-0.089	0.19	-9999	-0.48	70	70
alphaM/beta2 Integrin	-0.1	0.17	-9999	-0.42	65	65
JAM3 homodimer	0.014	0	-9999	-10000	0	0
ICAM2	0.013	0.024	-9999	-0.5	1	1
ICAM1	-0.029	0.15	-9999	-0.52	38	38
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.099	0.17	-9999	-0.42	65	65
cell adhesion	-0.078	0.17	-9999	-0.47	66	66
NFKB1	-0.16	0.27	-9999	-0.65	74	74
THY1	-0.003	0.1	-9999	-0.57	14	14
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.073	0.14	-9999	-0.33	102	102
alphaM/beta2 Integrin/LRP/tPA	-0.087	0.18	-9999	-0.46	62	62
IL6	-0.22	0.35	-9999	-0.8	94	94
ITGB2	-0.048	0.16	-9999	-0.58	36	36
elevation of cytosolic calcium ion concentration	-0.11	0.21	-9999	-0.52	76	76
alphaM/beta2 Integrin/JAM2/JAM3	-0.055	0.15	-9999	-0.47	47	47
JAM2	0.013	0.029	-9999	-0.61	1	1
alphaM/beta2 Integrin/ICAM1	-0.096	0.18	-9999	-0.53	45	45
alphaM/beta2 Integrin/uPA/Plg	-0.1	0.19	-9999	-0.45	84	84
RhoA/GTP	-0.091	0.16	-9999	-0.42	50	50
positive regulation of phagocytosis	-0.11	0.19	-9999	-0.6	44	44
Ron/MSP	-0.037	0.12	-9999	-0.42	41	41
alphaM/beta2 Integrin/uPAR/uPA	-0.11	0.21	-9999	-0.52	76	76
alphaM/beta2 Integrin/uPAR	-0.089	0.19	-9999	-0.48	74	74
PLAU	-0.061	0.19	-9999	-0.52	66	66
PLAT	-0.049	0.17	-9999	-0.5	57	57
actin filament polymerization	-0.085	0.15	-9999	-0.4	42	42
MST1	-0.029	0.16	-9999	-0.58	34	34
alphaM/beta2 Integrin/lipoprotein(a)	-0.12	0.19	-9999	-0.45	82	82
TNF	-0.24	0.36	-9999	-0.81	105	105
RAP1B	0.013	0.024	-9999	-0.5	1	1
alphaM/beta2 Integrin/uPA	-0.11	0.2	-9999	-0.48	87	87
fibrinolysis	-0.1	0.19	-9999	-0.45	84	84
HCK	-0.01	0.11	-9999	-0.55	20	20
dendritic cell antigen processing and presentation	-0.099	0.17	-9999	-0.42	65	65
VTN	-0.012	0.12	-9999	-0.56	21	21
alphaM/beta2 Integrin/CYR61	-0.14	0.23	-9999	-0.47	123	123
LPA	-0.024	0.13	-9999	-0.5	31	31
LRP1	0.014	0	-9999	-10000	0	0
cell migration	-0.15	0.22	-9999	-0.47	108	108
FN1	-0.004	0.096	-9999	-0.5	17	17
alphaM/beta2 Integrin/Thy1	-0.077	0.17	-9999	-0.49	61	61
MPO	-0.13	0.25	-9999	-0.55	115	115
KNG1	-0.019	0.11	-9999	-0.5	22	22
RAP1/GDP	-0.001	0.014	-9999	-0.29	1	1
ROCK1	-0.078	0.15	-9999	-0.43	32	32
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.04	-9999	-0.5	3	3
CTGF	-0.024	0.14	-9999	-0.54	32	32
alphaM/beta2 Integrin/Hck	-0.08	0.21	-9999	-0.58	54	54
ITGAM	-0.047	0.16	-9999	-0.62	34	34
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.095	0.22	-9999	-0.58	58	58
HP	-0.1	0.23	-9999	-0.54	100	100
leukocyte adhesion	-0.11	0.18	-9999	-0.57	45	45
SELP	-0.03	0.14	-9999	-0.5	37	37

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.095	0.22	-10000	0	-0.57	47	47
PTK2B	-0.011	0.11	-10000	0	-0.5	23	23
mol:Ca2+	-0.059	0.23	-10000	0	-0.76	28	28
EDN1	-0.082	0.19	-10000	0	-0.5	55	55
EDN3	-0.017	0.14	-10000	0	-0.6	24	24
EDN2	-0.013	0.094	-10000	0	-0.5	17	17
HRAS/GDP	-0.094	0.21	-10000	0	-0.53	51	51
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.053	0.16	-10000	0	-0.41	44	44
ADCY4	-0.11	0.23	-10000	0	-0.52	81	81
ADCY5	-0.12	0.25	-10000	0	-0.57	80	80
ADCY6	-0.1	0.22	-10000	0	-0.51	77	77
ADCY7	-0.1	0.22	-10000	0	-0.51	77	77
ADCY1	-0.16	0.25	-10000	0	-0.54	109	109
ADCY2	-0.11	0.24	-10000	0	-0.53	83	83
ADCY3	-0.1	0.22	-10000	0	-0.51	77	77
ADCY8	-0.14	0.26	-10000	0	-0.54	103	103
ADCY9	-0.1	0.22	-10000	0	-0.52	77	77
arachidonic acid secretion	-0.093	0.22	-10000	0	-0.52	64	64
ETB receptor/Endothelin-1/Gq/GTP	-0.046	0.16	-10000	0	-0.45	37	37
GNAO1	0.006	0.07	-10000	0	-0.61	6	6
HRAS	0.013	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.097	0.21	0.26	21	-0.55	45	66
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.23	0.25	20	-0.54	80	100
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.2	0.33	-10000	0	-0.62	151	151
EDNRB	-0.044	0.18	-10000	0	-0.6	43	43
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.12	0.26	-10000	0	-0.68	56	56
CYSLTR1	-0.11	0.25	-10000	0	-0.66	50	50
SLC9A1	-0.068	0.1	-10000	0	-0.32	30	30
mol:GDP	-0.11	0.23	-10000	0	-0.54	64	64
SLC9A3	-0.093	0.26	-10000	0	-0.69	56	56
RAF1	-0.11	0.23	-10000	0	-0.54	63	63
JUN	-0.043	0.19	-10000	0	-0.6	24	24
JAK2	-0.095	0.22	-10000	0	-0.57	47	47
mol:IP3	-0.06	0.18	-10000	0	-0.49	38	38
ETA receptor/Endothelin-1	-0.14	0.25	0.3	21	-0.58	67	88
PLCB1	-0.011	0.12	-10000	0	-0.61	18	18
PLCB2	-0.011	0.12	-10000	0	-0.58	18	18
ETA receptor/Endothelin-3	-0.074	0.16	-10000	0	-0.49	50	50
FOS	-0.14	0.33	-10000	0	-0.85	66	66
Gai/GDP	0.001	0.13	-10000	0	-1	6	6
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.12	0.25	-10000	0	-0.56	79	79
BCAR1	0.013	0.029	-10000	0	-0.61	1	1
PRKCB1	-0.059	0.17	-10000	0	-0.47	39	39
GNAQ	0.014	0.007	-10000	0	-10000	0	0
GNAZ	0.013	0.029	-10000	0	-0.61	1	1
GNAL	-0.051	0.19	-10000	0	-0.6	49	49
Gs family/GDP	-0.15	0.21	-10000	0	-0.52	86	86
ETA receptor/Endothelin-1/Gq/GTP	-0.053	0.15	-10000	0	-0.39	44	44
MAPK14	-0.038	0.16	-10000	0	-0.53	24	24
TRPC6	-0.063	0.25	-10000	0	-0.84	26	26
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.008	0.12	-10000	0	-0.61	17	17
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.049	0.17	-10000	0	-0.48	34	34
ETB receptor/Endothelin-2	-0.044	0.15	-10000	0	-0.42	59	59
ETB receptor/Endothelin-3	-0.048	0.17	-10000	0	-0.47	61	61
ETB receptor/Endothelin-1	-0.097	0.2	-10000	0	-0.52	62	62
MAPK3	-0.13	0.3	-10000	0	-0.75	69	69
MAPK1	-0.13	0.3	-10000	0	-0.74	70	70
Rac1/GDP	-0.094	0.21	-10000	0	-0.53	51	51
cAMP biosynthetic process	-0.12	0.24	-10000	0	-0.53	89	89
MAPK8	-0.058	0.21	-10000	0	-0.63	31	31
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.023	0.13	-10000	0	-0.4	28	28
p130Cas/CRK/Src/PYK2	-0.098	0.23	-10000	0	-0.58	52	52
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.094	0.21	-10000	0	-0.54	50	50
COL1A2	-0.13	0.29	-10000	0	-0.69	74	74
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.067	0.14	-10000	0	-0.45	44	44
mol:DAG	-0.06	0.18	-10000	0	-0.5	37	37
MAP2K2	-0.12	0.25	-10000	0	-0.59	71	71
MAP2K1	-0.12	0.25	-10000	0	-0.6	69	69
EDNRA	-0.067	0.18	-10000	0	-0.52	41	41
positive regulation of muscle contraction	-0.073	0.19	-10000	0	-0.51	45	45
Gq family/GDP	-0.12	0.2	-10000	0	-0.57	50	50
HRAS/GTP	-0.1	0.22	-10000	0	-0.51	63	63
PRKCH	-0.051	0.17	-10000	0	-0.52	28	28
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.051	0.17	-10000	0	-0.5	32	32
PRKCB	-0.09	0.2	-10000	0	-0.5	57	57
PRKCE	-0.056	0.18	-10000	0	-0.49	36	36
PRKCD	-0.066	0.2	-10000	0	-0.56	41	41
PRKCG	-0.15	0.23	-10000	0	-0.5	94	94
regulation of vascular smooth muscle contraction	-0.16	0.38	-10000	0	-1	63	63
PRKCQ	-0.062	0.19	-10000	0	-0.52	43	43
PLA2G4A	-0.1	0.24	-10000	0	-0.57	64	64
GNA14	-0.018	0.13	-10000	0	-0.58	25	25
GNA15	-0.011	0.12	-10000	0	-0.58	19	19
GNA12	0.013	0.029	-10000	0	-0.61	1	1
GNA11	0.004	0.076	-10000	0	-0.61	7	7
Rac1/GTP	-0.096	0.2	0.26	21	-0.54	45	66
MMP1	0.013	0.17	-10000	0	-0.42	43	43

×

Caspase cascade in apoptosis

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
TOP1	-0.051	0.16	0.2	2	-0.33	90	92
ACTA1	-0.074	0.19	0.25	1	-0.41	93	94
NUMA1	-0.051	0.16	0.21	1	-0.34	87	88
SPTAN1	-0.063	0.19	0.25	3	-0.41	87	90
LIMK1	-0.063	0.19	0.25	3	-0.41	87	90
BIRC3	-0.035	0.16	-10000	0	-0.56	40	40
BIRC2	0.014	0	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.092	0.21	-10000	0	-0.4	132	132
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.051	0.16	0.21	1	-0.34	87	88
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.062	0.19	0.25	3	-0.4	87	90
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.07	0.19	0.25	1	-0.41	90	91
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	-0.19	0.3	-10000	0	-0.66	125	125
BID	-0.044	0.12	-10000	0	-0.24	98	98
MAP3K1	-0.016	0.071	-10000	0	-0.22	6	6
TRADD	0.013	0.029	-10000	0	-0.61	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.007	0.02	-10000	0	-0.35	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.065	0.19	0.25	3	-0.41	88	91
CASP9	0.013	0.024	-10000	0	-0.5	1	1
DNA repair	0.004	0.063	-10000	0	-0.19	19	19
neuron apoptosis	0.005	0.048	-10000	0	-0.43	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.055	0.18	0.24	2	-0.4	81	83
APAF1	0.014	0	-10000	0	-10000	0	0
CASP6	-0.033	0.12	-10000	0	-0.68	5	5
TRAF2	0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.053	0.18	-10000	0	-0.4	79	79
CASP7	0.02	0.079	0.27	35	-10000	0	35
KRT18	-0.085	0.2	-10000	0	-0.6	57	57
apoptosis	-0.077	0.19	0.26	1	-0.42	70	71
DFFA	-0.063	0.19	0.25	3	-0.41	85	88
DFFB	-0.063	0.19	0.25	3	-0.41	86	89
PARP1	-0.004	0.063	0.19	19	-10000	0	19
actin filament polymerization	0.05	0.18	0.38	81	-0.25	1	82
TNF	-0.16	0.26	-10000	0	-0.55	142	142
CYCS	-0.027	0.084	-10000	0	-0.21	38	38
SATB1	-0.028	0.12	-10000	0	-0.55	9	9
SLK	-0.064	0.19	0.25	3	-0.41	86	89
p15 BID/BAX	-0.032	0.1	-10000	0	-0.32	19	19
CASP2	-0.018	0.11	-10000	0	-0.39	12	12
JNK cascade	0.016	0.071	0.22	6	-10000	0	6
CASP3	-0.075	0.2	0.25	4	-0.43	91	95
LMNB2	-0.015	0.096	-10000	0	-0.4	9	9
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	-0.016	0.12	-10000	0	-0.5	27	27
Mammalian IAPs/DIABLO	-0.025	0.083	-10000	0	-0.33	23	23
negative regulation of DNA binding	-0.19	0.3	-10000	0	-0.65	125	125
stress fiber formation	-0.063	0.19	0.25	3	-0.4	86	89
GZMB	-0.12	0.24	-10000	0	-0.48	132	132
CASP1	-0.009	0.094	-10000	0	-0.31	39	39
LMNB1	-0.023	0.11	-10000	0	-0.39	16	16
APP	0.005	0.048	-10000	0	-0.43	1	1
TNFRSF1A	0.003	0.079	-10000	0	-0.56	9	9
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0	0.069	-10000	0	-0.36	16	16
VIM	-0.083	0.19	0.23	8	-0.4	92	100
LMNA	-0.015	0.095	-10000	0	-0.39	9	9
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.028	0.12	-10000	0	-0.38	17	17
LRDD	0.007	0.068	-10000	0	-0.59	6	6
SREBF1	-0.074	0.19	0.25	2	-0.4	95	97
APAF-1/Caspase 9	-0.007	0.044	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.05	0.15	0.21	1	-0.33	87	88
CFL2	-0.052	0.18	0.25	1	-0.39	81	82
GAS2	-0.073	0.2	0.25	2	-0.41	93	95
positive regulation of apoptosis	-0.015	0.1	-10000	0	-0.36	13	13
PRF1	-0.07	0.2	-10000	0	-0.55	69	69

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.049	-10000	0	-0.44	4	4
fibroblast growth factor receptor signaling pathway	-0.006	0.049	-10000	0	-0.43	4	4
LAMA1	-0.058	0.2	-10000	0	-0.58	56	56
PRNP	0.013	0.029	-10000	0	-0.61	1	1
GPC1/SLIT2	-0.097	0.17	-10000	0	-0.39	115	115
SMAD2	0.03	0.048	-10000	0	-0.42	2	2
GPC1/PrPc/Cu2+	-0.003	0.032	-10000	0	-0.31	5	5
GPC1/Laminin alpha1	-0.053	0.14	-10000	0	-0.43	58	58
TDGF1	-0.081	0.22	-10000	0	-0.58	74	74
CRIPTO/GPC1	-0.07	0.16	-10000	0	-0.43	75	75
APP/GPC1	-0.003	0.032	-10000	0	-0.35	4	4
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.035	0.15	-10000	0	-0.37	76	76
FLT1	0.013	0.029	-10000	0	-0.61	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.007	0.048	-10000	0	-0.32	10	10
SERPINC1	-0.003	0.087	-10000	0	-0.5	14	14
FYN	-0.032	0.15	-10000	0	-0.36	75	75
FGR	-0.034	0.15	-10000	0	-0.36	78	78
positive regulation of MAPKKK cascade	-0.078	0.2	-10000	0	-0.48	67	67
SLIT2	-0.12	0.24	-10000	0	-0.55	112	112
GPC1/NRG	-0.13	0.19	-10000	0	-0.41	148	148
NRG1	-0.17	0.27	-10000	0	-0.57	146	146
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.016	0.068	-10000	0	-0.3	25	25
LYN	-0.039	0.15	-10000	0	-0.39	58	58
mol:Spermine	0.009	0.034	-10000	0	-0.36	4	4
cell growth	-0.006	0.049	-10000	0	-0.43	4	4
BMP signaling pathway	-0.01	0.047	0.49	4	-10000	0	4
SRC	-0.032	0.15	-10000	0	-0.36	75	75
TGFBR1	0.012	0.037	-10000	0	-0.55	2	2
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.085	0.2	-10000	0	-0.51	81	81
GPC1	0.01	0.047	-10000	0	-0.5	4	4
TGFBR1 (dimer)	0.012	0.037	-10000	0	-0.55	2	2
VEGFA	-0.009	0.11	-10000	0	-0.5	21	21
BLK	-0.11	0.2	-10000	0	-0.35	165	165
HCK	-0.047	0.17	-10000	0	-0.37	89	89
FGF2	0.011	0.047	-10000	0	-0.57	3	3
FGFR1	0.012	0.041	-10000	0	-0.61	2	2
VEGFR1 homodimer	0.013	0.029	-10000	0	-0.61	1	1
TGFBR2	0.009	0.053	-10000	0	-0.5	5	5
cell death	-0.003	0.032	-10000	0	-0.34	4	4
ATIII/GPC1	-0.013	0.067	-10000	0	-0.35	18	18
PLA2G2A/GPC1	-0.066	0.14	-10000	0	-0.37	82	82
LCK	-0.095	0.2	-10000	0	-0.38	142	142
neuron differentiation	-0.13	0.19	-10000	0	-0.41	148	148
PrPc/Cu2+	-0.001	0.021	-10000	0	-0.45	1	1
APP	0.014	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.009	0.053	-10000	0	-0.49	5	5

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.038	0.1	-9999	-0.32	43	43
RGS9BP	0.002	0.084	-9999	-0.6	9	9
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.011	0.037	-9999	-0.55	2	2
mol:Na +	-0.1	0.15	-9999	-0.32	146	146
mol:ADP	0.017	0.044	-9999	-0.36	6	6
GNAT2	0.009	0.034	-9999	-0.5	2	2
RGS9-1/Gbeta5/R9AP	-0.04	0.12	-9999	-0.4	43	43
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.013	0.062	-9999	-0.31	19	19
GRK7	0.008	0.047	-9999	-0.5	4	4
CNGB3	-0.011	0.098	-9999	-0.5	18	18
Cone Metarhodopsin II/X-Arrestin	-0.001	0.017	-9999	-0.36	1	1
mol:Ca2+	-0.14	0.2	-9999	-0.35	210	210
Cone PDE6	-0.045	0.12	-9999	-0.36	33	33
Cone Metarhodopsin II	-0.004	0.032	-9999	-0.28	6	6
Na + (4 Units)	-0.16	0.19	-9999	-0.35	210	210
GNAT2/GDP	-0.035	0.11	-9999	-0.34	43	43
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.003	0.066	-9999	-0.27	24	24
Cone Transducin	-0.041	0.11	-9999	-0.34	43	43
SLC24A2	-0.11	0.24	-9999	-0.56	103	103
GNB3/GNGT2	-0.052	0.14	-9999	-0.41	58	58
GNB3	-0.031	0.16	-9999	-0.58	35	35
GNAT2/GTP	-0.002	0.023	-9999	-0.36	2	2
CNGA3	-0.14	0.25	-9999	-0.54	129	129
ARR3	0.002	0.024	-9999	-0.5	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.15	-9999	-0.33	146	146
mol:Pi	-0.04	0.12	-9999	-0.4	43	43
Cone CNG Channel	-0.092	0.14	-9999	-0.38	37	37
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.24	-9999	-0.56	103	103
RGS9	-0.042	0.18	-9999	-0.59	43	43
PDE6C	0.002	0.052	-9999	-0.5	5	5
GNGT2	-0.014	0.13	-9999	-0.56	23	23
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.01	0.098	-9999	-0.5	18	18

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.18	0.38	-10000	0	-0.96	57	57
PCK1	-0.25	0.44	-10000	0	-1.1	75	75
HNF4A	-0.21	0.42	-10000	0	-1.1	59	59
KCNJ11	-0.25	0.51	-10000	0	-1.2	78	78
AKT1	-0.077	0.17	-10000	0	-0.42	21	21
response to starvation	-0.003	0.023	-10000	0	-10000	0	0
DLK1	-0.25	0.45	-10000	0	-1	91	91
NKX2-1	-0.076	0.22	-10000	0	-0.67	23	23
ACADM	-0.18	0.38	-10000	0	-0.96	56	56
TAT	-0.23	0.42	-10000	0	-1.1	59	59
CEBPB	-0.005	0.11	-10000	0	-0.58	15	15
CEBPA	-0.016	0.13	-10000	0	-0.58	24	24
TTR	-0.16	0.28	-10000	0	-0.78	45	45
PKLR	-0.19	0.4	-10000	0	-0.94	66	66
APOA1	-0.24	0.48	-10000	0	-1.2	61	61
CPT1C	-0.18	0.39	-10000	0	-0.96	59	59
ALAS1	-0.063	0.2	-10000	0	-0.88	2	2
TFRC	-0.17	0.32	-10000	0	-0.78	53	53
FOXF1	-0.005	0.094	-10000	0	-0.52	14	14
NF1	0.02	0.041	-10000	0	-0.6	2	2
HNF1A (dimer)	0.011	0.041	-10000	0	-0.67	1	1
CPT1A	-0.18	0.39	-10000	0	-0.98	57	57
HMGCS1	-0.18	0.38	-10000	0	-0.97	56	56
NR3C1	-0.023	0.076	-10000	0	-0.3	1	1
CPT1B	-0.2	0.41	-10000	0	-0.97	70	70
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.025	-10000	0	-10000	0	0
GCK	-0.25	0.48	-10000	0	-1	98	98
CREB1	-0.004	0.055	-10000	0	-10000	0	0
IGFBP1	-0.26	0.51	-10000	0	-1.3	78	78
PDX1	-0.08	0.21	-10000	0	-0.72	8	8
UCP2	-0.2	0.42	-10000	0	-0.96	77	77
ALDOB	-0.19	0.43	-10000	0	-1	67	67
AFP	-0.093	0.18	-10000	0	-0.58	28	28
BDH1	-0.21	0.44	-10000	0	-1.1	73	73
HADH	-0.18	0.4	-10000	0	-0.98	60	60
F2	-0.21	0.42	-10000	0	-1.1	49	49
HNF1A	0.011	0.041	-10000	0	-0.67	1	1
G6PC	-0.072	0.22	-10000	0	-0.79	23	23
SLC2A2	-0.092	0.22	-10000	0	-0.57	20	20
INS	0.014	0.089	0.24	7	-0.56	4	11
FOXA1	-0.053	0.17	-10000	0	-0.53	43	43
FOXA3	-0.13	0.24	-10000	0	-0.56	91	91
FOXA2	-0.22	0.46	-10000	0	-1	75	75
ABCC8	-0.27	0.53	-10000	0	-1.2	85	85
ALB	-0.13	0.3	-10000	0	-1.1	34	34

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.024	0.099	-9999	-0.44	25	25
VLDLR	-0.003	0.1	-9999	-0.57	14	14
CRKL	0.014	0	-9999	-10000	0	0
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ITGA3	-0.011	0.11	-9999	-0.51	22	22
RELN/VLDLR/Fyn	-0.098	0.16	-9999	-0.34	132	132
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.053	-9999	-10000	0	0
AKT1	-0.067	0.15	-9999	-0.48	24	24
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.087	0.22	-9999	-0.58	79	79
RELN/LRP8/DAB1	-0.13	0.18	-9999	-0.39	120	120
LRPAP1/LRP8	-0.001	0.02	-9999	-0.44	1	1
RELN/LRP8/DAB1/Fyn	-0.12	0.17	-9999	-0.36	120	120
DAB1/alpha3/beta1 Integrin	-0.13	0.17	-9999	-0.54	43	43
long-term memory	-0.29	0.29	-9999	-0.65	151	151
DAB1/LIS1	-0.12	0.16	-9999	-0.55	31	31
DAB1/CRLK/C3G	-0.11	0.16	-9999	-0.53	31	31
PIK3CA	0.014	0	-9999	-10000	0	0
DAB1/NCK2	-0.12	0.17	-9999	-0.55	31	31
ARHGEF2	0.013	0.029	-9999	-0.61	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.17	0.27	-9999	-0.56	147	147
CDK5R1	-0.019	0.14	-9999	-0.6	25	25
RELN	-0.14	0.25	-9999	-0.56	122	122
PIK3R1	0.014	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.088	0.15	-9999	-0.33	122	122
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.21	0.24	-9999	-0.61	93	93
MAPK8	0.001	0.09	-9999	-0.61	10	10
RELN/VLDLR/DAB1	-0.14	0.19	-9999	-0.4	127	127
ITGB1	0.012	0.033	-9999	-0.5	2	2
MAP1B	-0.1	0.19	-9999	-0.57	31	31
RELN/LRP8	-0.088	0.15	-9999	-0.37	69	69
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.22	0.24	-9999	-0.6	95	95
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.018	0.082	-9999	-0.37	23	23
RAP1A	-0.068	0.17	-9999	-0.49	31	31
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.057	-9999	-0.61	4	4
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.19	0.27	-9999	-0.55	165	165
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.039	0.14	-9999	-0.43	26	26
neuron adhesion	-0.062	0.18	-9999	-0.48	36	36
LRP8	0.013	0.029	-9999	-0.61	1	1
GSK3B	-0.055	0.15	-9999	-0.46	23	23
RELN/VLDLR/DAB1/Fyn	-0.13	0.18	-9999	-0.37	127	127
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.08	0.16	-9999	-0.31	127	127
CDK5	0.014	0	-9999	-10000	0	0
MAPT	0.01	0.084	-9999	-0.55	9	9
neuron migration	-0.065	0.19	-9999	-0.52	33	33
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.039	0.14	-9999	-0.43	26	26
RELN/VLDLR	-0.087	0.14	-9999	-0.34	79	79

×

Visual signal transduction: Rods

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
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.023	0.089	-9999	-0.36	30	30
Metarhodopsin II/Arrestin	-0.033	0.1	-9999	-0.33	47	47
PDE6G/GNAT1/GTP	-0.048	0.12	-9999	-0.34	65	65
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.022	0.13	-9999	-0.5	30	30
GRK1	0.011	0.037	-9999	-0.55	2	2
CNG Channel	-0.2	0.2	-9999	-0.55	75	75
mol:Na +	-0.2	0.2	-9999	-0.52	92	92
mol:ADP	0.011	0.037	-9999	-0.55	2	2
RGS9-1/Gbeta5/R9AP	-0.04	0.12	-9999	-0.4	43	43
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.21	0.21	-9999	-0.54	92	92
CNGB1	-0.18	0.26	-9999	-0.53	166	166
RDH5	-0.018	0.12	-9999	-0.5	29	29
SAG	0.003	0.006	-9999	-10000	0	0
mol:Ca2+	-0.17	0.21	-9999	-0.5	92	92
Na + (4 Units)	-0.19	0.19	-9999	-0.49	92	92
RGS9	-0.042	0.18	-9999	-0.59	43	43
GNB1/GNGT1	-0.001	0.016	-9999	-0.35	1	1
GNAT1/GDP	-0.049	0.12	-9999	-0.34	45	45
GUCY2D	-0.007	0.09	-9999	-0.5	15	15
GNGT1	-0.001	0.023	-9999	-0.5	1	1
GUCY2F	0.005	0.047	-9999	-0.5	4	4
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.067	0.16	-9999	-0.37	70	70
mol:11-cis-retinal	-0.018	0.12	-9999	-0.5	29	29
mol:cGMP	-0.091	0.17	-9999	-0.38	88	88
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.06	0.14	-9999	-0.37	75	75
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.054	0.19	-9999	-0.57	54	54
Metarhodopsin II	-0.031	0.09	-9999	-0.29	49	49
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.11	0.18	-9999	-0.41	90	90
RGS9BP	0.002	0.084	-9999	-0.6	9	9
Metarhodopsin II/Transducin	-0.014	0.079	-9999	-0.3	17	17
GCAP Family/Ca ++	-0.1	0.17	-9999	-0.35	137	137
PDE6A/B	-0.074	0.16	-9999	-0.4	85	85
mol:Pi	-0.04	0.12	-9999	-0.4	43	43
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.018	0.07	-9999	-0.28	30	30
PDE6B	-0.037	0.16	-9999	-0.55	42	42
PDE6A	-0.043	0.17	-9999	-0.54	47	47
PDE6G	-0.034	0.16	-9999	-0.57	38	38
RHO	-0.044	0.16	-9999	-0.53	47	47
PDE6	-0.1	0.17	-9999	-0.58	29	29
GUCA1A	-0.14	0.25	-9999	-0.55	127	127
GC2/GCAP Family	-0.1	0.17	-9999	-0.4	83	83
GUCA1C	-0.013	0.091	-9999	-0.5	16	16
GUCA1B	-0.007	0.11	-9999	-0.6	16	16

×

HIF-1-alpha transcription factor network

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
PKM2	-0.017	0.49	-9999	-1.1	52	52
HDAC7	0.017	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.14	0.33	-9999	-0.86	54	54
SMAD4	0.016	0.003	-9999	-10000	0	0
ID2	-0.017	0.49	-9999	-1.1	52	52
AP1	-0.065	0.18	-9999	-0.43	88	88
ABCG2	-0.018	0.49	-9999	-1.1	52	52
HIF1A	0.025	0.09	-9999	-0.56	1	1
TFF3	-0.056	0.51	-9999	-1.1	61	61
GATA2	-0.006	0.11	-9999	-0.58	16	16
AKT1	0.019	0.1	-9999	-10000	0	0
response to hypoxia	0.001	0.11	-9999	-0.23	19	19
MCL1	-0.017	0.49	-9999	-1.1	52	52
NDRG1	-0.021	0.5	-9999	-1.1	53	53
SERPINE1	-0.092	0.55	-9999	-1.1	75	75
FECH	-0.017	0.49	-9999	-1.1	52	52
FURIN	-0.017	0.49	-9999	-1.1	52	52
NCOA2	-0.023	0.15	-9999	-0.61	29	29
EP300	0.034	0.18	-9999	-0.34	32	32
HMOX1	-0.027	0.51	-9999	-1.1	55	55
BHLHE40	-0.026	0.51	-9999	-1.1	56	56
BHLHE41	-0.024	0.51	-9999	-1.1	55	55
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.013	0.059	-9999	-0.38	6	6
ENG	0.09	0.13	-9999	-0.52	7	7
JUN	0.003	0.076	-9999	-0.51	10	10
RORA	-0.017	0.49	-9999	-1	53	53
ABCB1	-0.04	0.096	-9999	-1.1	2	2
TFRC	-0.023	0.5	-9999	-1.1	55	55
CXCR4	-0.029	0.51	-9999	-1.1	57	57
TF	-0.048	0.53	-9999	-1.1	58	58
CITED2	-0.018	0.49	-9999	-1.1	52	52
HIF1A/ARNT	-0.19	0.51	-9999	-1.2	58	58
LDHA	-0.031	0.094	-9999	-0.68	6	6
ETS1	-0.021	0.5	-9999	-1.1	54	54
PGK1	-0.017	0.49	-9999	-1.1	52	52
NOS2	-0.043	0.52	-9999	-1.1	60	60
ITGB2	-0.037	0.52	-9999	-1.1	58	58
ALDOA	-0.017	0.49	-9999	-1.1	52	52
Cbp/p300/CITED2	-0.086	0.5	-9999	-1.1	54	54
FOS	-0.093	0.22	-9999	-0.56	87	87
HK2	-0.03	0.51	-9999	-1.1	56	56
SP1	0.024	0.005	-9999	-10000	0	0
GCK	-0.068	0.48	-9999	-1.1	63	63
HK1	-0.017	0.49	-9999	-1.1	52	52
NPM1	-0.017	0.49	-9999	-1.1	52	52
EGLN1	-0.017	0.49	-9999	-1.1	52	52
CREB1	0.023	0.003	-9999	-10000	0	0
PGM1	-0.017	0.49	-9999	-1.1	52	52
SMAD3	0.016	0.003	-9999	-10000	0	0
EDN1	-0.047	0.33	-9999	-1	28	28
IGFBP1	-0.078	0.53	-9999	-1.1	65	65
VEGFA	0.017	0.41	-9999	-0.85	43	43
HIF1A/JAB1	-0.007	0.031	-9999	-0.41	1	1
CP	-0.1	0.55	-9999	-1.1	72	72
CXCL12	-0.021	0.5	-9999	-1.1	53	53
COPS5	0.016	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.018	0.49	-9999	-1.1	52	52
EGLN3	-0.02	0.5	-9999	-1.1	52	52
CA9	-0.053	0.53	-9999	-1.1	59	59
TERT	-0.084	0.51	-9999	-1.1	69	69
ENO1	-0.017	0.49	-9999	-1.1	52	52
PFKL	-0.017	0.49	-9999	-1.1	52	52
NCOA1	0.015	0.001	-9999	-10000	0	0
ADM	-0.053	0.52	-9999	-1.1	61	61
ARNT	0.015	0.089	-9999	-0.66	1	1
HNF4A	-0.043	0.14	-9999	-0.49	37	37
ADFP	-0.066	0.47	-9999	-1	55	55
SLC2A1	0.025	0.39	-9999	-0.79	41	41
LEP	-0.053	0.48	-9999	-1.1	52	52
HIF1A/ARNT/Cbp/p300	-0.15	0.35	-9999	-0.86	61	61
EPO	0.027	0.36	-9999	-0.83	28	28
CREBBP	0.037	0.17	-9999	-0.33	27	27
HIF1A/ARNT/Cbp/p300/HDAC7	-0.14	0.34	-9999	-0.89	53	53
PFKFB3	-0.018	0.49	-9999	-1.1	52	52
NT5E	-0.026	0.5	-9999	-1.1	57	57

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.014	0	-9999	-10000	0	0
EGFR	-0.083	0.22	-9999	-0.56	79	79
EGF/EGFR	-0.11	0.17	-9999	-0.37	103	103
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.078	0.14	-9999	-0.35	76	76
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.021	0.14	-9999	-0.56	29	29
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.047	0.18	-9999	-0.56	49	49
EGF/EGFR dimer/SHC	-0.094	0.17	-9999	-0.37	117	117
mol:GDP	-0.077	0.14	-9999	-0.35	76	76
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.037	0.16	-9999	-0.53	43	43
GRB2/SOS1	-0.001	0.016	-9999	-0.35	1	1
HRAS/GTP	-0.07	0.13	-9999	-0.5	16	16
SHC1	0.009	0.053	-9999	-0.5	5	5
HRAS/GDP	-0.071	0.13	-9999	-0.51	16	16
FRAP1	-0.044	0.15	-9999	-0.34	76	76
EGF/EGFR dimer	-0.11	0.2	-9999	-0.44	115	115
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.024	-9999	-0.5	1	1
ETA receptor/Endothelin-1	-0.06	0.15	-9999	-0.4	69	69

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.11	0.18	-10000	0	-0.39	129	129
CRKL	-0.045	0.13	-10000	0	-0.5	10	10
mol:PIP3	-0.018	0.026	0.53	1	-10000	0	1
AKT1	0.003	0.024	0.37	1	-0.34	1	2
PTK2B	-0.011	0.11	-10000	0	-0.5	23	23
RAPGEF1	-0.035	0.13	-10000	0	-0.46	10	10
RANBP10	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.14	0.19	-10000	0	-0.37	177	177
MAP3K5	-0.038	0.14	-10000	0	-0.42	21	21
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.13	0.17	-10000	0	-0.4	95	95
AP1	-0.088	0.17	-10000	0	-0.41	88	88
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.009	0.053	-10000	0	-0.5	5	5
apoptosis	-0.097	0.24	-10000	0	-0.77	50	50
STAT3 (dimer)	-0.048	0.14	-10000	0	-0.42	15	15
GAB1/CRKL/SHP2/PI3K	-0.058	0.097	-10000	0	-0.45	9	9
INPP5D	0.008	0.058	-10000	0	-0.54	5	5
CBL/CRK	-0.035	0.13	-10000	0	-0.46	10	10
PTPN11	0.014	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.029	-10000	0	-0.61	1	1
ELK1	-0.057	0.092	-10000	0	-0.2	129	129
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.049	0.077	-10000	0	-0.34	10	10
PAK1	-0.015	0.081	0.35	1	-0.31	6	7
HGF/MET/RANBP10	-0.14	0.19	-10000	0	-0.37	177	177
HRAS	-0.1	0.24	-10000	0	-0.65	61	61
DOCK1	-0.037	0.13	-10000	0	-0.46	10	10
GAB1	-0.056	0.14	-10000	0	-0.3	84	84
CRK	-0.045	0.13	-10000	0	-0.29	66	66
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.13	0.22	-10000	0	-0.6	72	72
JUN	0.003	0.076	-10000	0	-0.51	10	10
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.074	0.13	-10000	0	-0.29	95	95
PIK3R1	0.014	0	-10000	0	-10000	0	0
cell morphogenesis	-0.018	0.14	-10000	0	-0.45	10	10
GRB2/SHC	-0.052	0.12	-10000	0	-0.45	14	14
FOS	-0.093	0.22	-10000	0	-0.56	87	87
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.057	0.092	-10000	0	-0.2	129	129
HGF/MET/MUC20	-0.14	0.2	-10000	0	-0.38	177	177
cell migration	-0.051	0.12	-10000	0	-0.44	14	14
GRB2	0.013	0.024	-10000	0	-0.5	1	1
CBL	0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.11	0.18	-10000	0	-0.39	129	129
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.061	0.14	-10000	0	-0.36	33	33
MET/MUC20	-0.11	0.18	-10000	0	-0.4	129	129
RAP1B	-0.025	0.12	-10000	0	-0.43	10	10
RAP1A	-0.025	0.12	-10000	0	-0.44	9	9
HGF/MET/RANBP9	-0.14	0.19	-10000	0	-0.37	177	177
RAF1	-0.089	0.22	-10000	0	-0.61	60	60
STAT3	-0.049	0.14	-10000	0	-0.42	15	15
cell proliferation	-0.062	0.18	-10000	0	-0.4	81	81
RPS6KB1	-0.02	0.05	-10000	0	-0.24	1	1
MAPK3	-0.058	0.083	-10000	0	-10000	0	0
MAPK1	-0.058	0.083	-10000	0	-0.21	2	2
RANBP9	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.02	0.14	-10000	0	-0.44	21	21
SRC	-0.048	0.13	-10000	0	-0.42	15	15
PI3K	-0.049	0.12	-10000	0	-0.27	60	60
MET/Glomulin	-0.088	0.16	-10000	0	-0.35	129	129
SOS1	0.014	0	-10000	0	-10000	0	0
MAP2K1	-0.075	0.21	-10000	0	-0.55	60	60
MET	-0.14	0.25	-10000	0	-0.55	129	129
MAP4K1	-0.046	0.14	-10000	0	-0.44	19	19
PTK2	0.014	0	-10000	0	-10000	0	0
MAP2K2	-0.074	0.21	-10000	0	-0.55	60	60
BAD	0.011	0.022	0.35	1	-0.31	1	2
MAP2K4	-0.027	0.13	-10000	0	-0.43	17	17
SHP2/GRB2/SOS1/GAB1	-0.088	0.14	-10000	0	-0.39	61	61
INPPL1	0.014	0	-10000	0	-10000	0	0
PXN	0.014	0	-10000	0	-10000	0	0
SH3KBP1	0.014	0	-10000	0	-10000	0	0
HGS	-0.06	0.12	-10000	0	-0.28	83	83
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.078	0.2	-10000	0	-0.52	80	80
RASA1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.029	-10000	0	-0.61	1	1
PTPRJ	0.012	0.037	-10000	0	-0.55	2	2
NCK/PLCgamma1	-0.049	0.12	-10000	0	-0.26	83	83
PDPK1	-0.007	0.027	0.42	1	-0.37	1	2
HGF/MET/SHIP	-0.14	0.2	-10000	0	-0.38	178	178

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.009	0.093	-9999	-0.38	25	25
NFATC2	-0.041	0.13	-9999	-0.36	66	66
NFATC3	0.011	0.034	-9999	-0.35	2	2
CD40LG	-0.15	0.29	-9999	-0.64	88	88
PTGS2	-0.18	0.32	-9999	-0.67	111	111
JUNB	-0.036	0.16	-9999	-0.52	43	43
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.029	-9999	-0.41	2	2
CaM/Ca2+	-0.006	0.029	-9999	-0.41	2	2
CALM1	0.01	0.038	-9999	-0.56	2	2
JUN	0.001	0.077	-9999	-0.51	10	10
mol:Ca2+	-0.005	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-9999	-10000	0	0
FOSL1	-0.095	0.22	-9999	-0.54	91	91
CREM	0.012	0.037	-9999	-0.55	2	2
Jun/NFAT1-c-4/p21SNFT	-0.12	0.18	-9999	-0.51	57	57
FOS	-0.096	0.23	-9999	-0.56	87	87
IFNG	-0.14	0.26	-9999	-0.59	80	80
AP-1/NFAT1-c-4	-0.16	0.32	-9999	-0.67	93	93
FASLG	-0.15	0.29	-9999	-0.61	93	93
NFAT1-c-4/ICER1	-0.055	0.15	-9999	-0.45	32	32
IL2RA	-0.16	0.3	-9999	-0.63	100	100
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.14	0.26	-9999	-0.59	75	75
JunB/Fra1/NFAT1-c-4	-0.14	0.2	-9999	-0.49	86	86
IL4	-0.14	0.26	-9999	-0.58	79	79
IL2	-0.008	0.015	-9999	-10000	0	0
IL3	-0.019	0.045	-9999	-0.89	1	1
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	-0.036	0.16	-9999	-0.54	42	42
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.029	-9999	-0.61	1	1

×

p75(NTR)-mediated 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
Sortilin/TRAF6	-0.002	0.029	-10000	0	-0.44	2	2
Necdin/E2F1	-0.051	0.14	-10000	0	-0.42	56	56
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.082	0.14	-10000	0	-0.56	11	11
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.18	-10000	0	-0.38	139	139
NT-4/5 (dimer)/p75(NTR)	-0.071	0.16	-10000	0	-0.41	81	81
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.049	0.16	-10000	0	-0.56	11	11
IKBKG	0.014	0	-10000	0	-10000	0	0
BDNF	-0.08	0.2	-10000	0	-0.51	83	83
MGDIs/NGR/p75(NTR)/LINGO1	-0.097	0.19	-10000	0	-0.4	113	113
FURIN	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.1	0.17	-10000	0	-0.35	134	134
LINGO1	-0.019	0.14	-10000	0	-0.61	25	25
Sortilin/TRAF6/NRIF	-0.001	0.016	-10000	0	-10000	0	0
proBDNF (dimer)	-0.08	0.2	-10000	0	-0.51	83	83
NTRK1	-0.008	0.11	-10000	0	-0.53	19	19
RTN4R	-0.036	0.17	-10000	0	-0.57	40	40
neuron apoptosis	-0.068	0.18	-10000	0	-0.48	39	39
IRAK1	0.014	0	-10000	0	-10000	0	0
SHC1	-0.08	0.19	-10000	0	-0.36	130	130
ARHGDIA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.094	0.16	-10000	0	-0.36	90	90
MAGEH1	0.005	0.076	-10000	0	-0.61	7	7
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.11	0.18	-10000	0	-0.4	107	107
Mammalian IAPs/DIABLO	-0.025	0.083	-10000	0	-0.33	23	23
proNGF (dimer)	-0.074	0.21	-10000	0	-0.57	69	69
MAGED1	0.014	0	-10000	0	-10000	0	0
APP	0.014	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.012	0.093	-10000	0	-0.5	16	16
ZNF274	0.014	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.057	0.16	-10000	0	-0.34	82	82
NGF	-0.074	0.21	-10000	0	-0.58	69	69
cell cycle arrest	-0.078	0.14	-10000	0	-0.32	83	83
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.034	0.13	-10000	0	-0.43	14	14
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.06	0.13	-10000	0	-0.34	82	82
NCSTN	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.099	0.17	-10000	0	-0.4	85	85
PSENEN	0.014	0	-10000	0	-10000	0	0
mol:ceramide	-0.062	0.17	-10000	0	-0.36	83	83
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.024	0.12	-10000	0	-0.39	18	18
p75(NTR)/beta APP	-0.058	0.14	-10000	0	-0.39	69	69
BEX1	-0.01	0.12	-10000	0	-0.61	18	18
mol:GDP	-0.087	0.18	-10000	0	-0.37	127	127
NGF (dimer)	-0.14	0.18	-10000	0	-0.39	116	116
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.087	0.17	-10000	0	-0.41	75	75
PIK3R1	0.014	0	-10000	0	-10000	0	0
RAC1/GTP	-0.085	0.15	-10000	0	-0.31	127	127
MYD88	0.008	0.062	-10000	0	-0.58	5	5
CHUK	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.1	0.17	-10000	0	-0.4	85	85
RHOB	0.011	0.041	-10000	0	-0.5	3	3
RHOA	0.014	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.02	0.084	-10000	0	-0.36	26	26
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	16	16
TP53	-0.051	0.17	-10000	0	-0.52	26	26
PRDM4	-0.062	0.17	-10000	0	-0.36	83	83
BDNF (dimer)	-0.16	0.2	-10000	0	-0.36	210	210
PIK3CA	0.014	0	-10000	0	-10000	0	0
SORT1	0.013	0.029	-10000	0	-0.61	1	1
activation of caspase activity	-0.081	0.14	-10000	0	-0.56	11	11
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.09	0.15	-10000	0	-0.36	84	84
RHOC	0.012	0.037	-10000	0	-0.55	2	2
XIAP	0.014	0	-10000	0	-10000	0	0
MAPK10	-0.047	0.17	-10000	0	-0.48	29	29
DIABLO	0.014	0	-10000	0	-10000	0	0
SMPD2	-0.062	0.17	-10000	0	-0.36	83	83
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.1	0.17	-10000	0	-0.36	128	128
PSEN1	0.014	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.016	-10000	0	-0.35	1	1
NT3 (dimer)/p75(NTR)	-0.071	0.16	-10000	0	-0.41	80	80
MAPK8	-0.05	0.17	-10000	0	-0.47	29	29
MAPK9	-0.045	0.17	-10000	0	-0.48	25	25
APAF1	0.014	0	-10000	0	-10000	0	0
NTF3	-0.008	0.092	-10000	0	-0.5	16	16
NTF4	-0.012	0.093	-10000	0	-0.5	16	16
NDN	-0.029	0.16	-10000	0	-0.61	32	32
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.076	0.13	-10000	0	-0.51	12	12
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.046	-10000	0	-0.38	6	6
RhoA-B-C/GTP	-0.099	0.17	-10000	0	-0.4	85	85
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.084	0.14	-10000	0	-0.39	53	53
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.091	0.16	-10000	0	-0.42	53	53
PRKACB	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.069	0.15	-10000	0	-0.37	86	86
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.035	0.16	-10000	0	-0.56	40	40
BIRC2	0.014	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.093	0.16	0.21	5	-0.38	89	94
BAD	-0.039	0.16	-10000	0	-0.46	27	27
RIPK2	0.014	0	-10000	0	-10000	0	0
NGFR	-0.07	0.2	-10000	0	-0.55	69	69
CYCS	-0.05	0.16	-10000	0	-0.54	12	12
ADAM17	0.008	0.064	-10000	0	-0.61	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.089	0.15	-10000	0	-0.36	83	83
BCL2L11	-0.04	0.17	-10000	0	-0.46	27	27
BDNF (dimer)/p75(NTR)	-0.12	0.2	-10000	0	-0.42	133	133
PI3K	-0.088	0.15	-10000	0	-0.36	82	82
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.089	0.15	-10000	0	-0.36	83	83
NDNL2	0.014	0	-10000	0	-10000	0	0
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKCI	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.12	0.2	-10000	0	-0.43	127	127
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.089	0.15	-10000	0	-0.36	83	83
TRAF6	0.013	0.029	-10000	0	-0.61	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.017	0.13	-10000	0	-0.57	25	25
PLG	-0.001	0.04	-10000	0	-0.5	3	3
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.098	0.19	-10000	0	-0.39	101	101
SQSTM1	0.014	0	-10000	0	-10000	0	0
NGFRAP1	0.014	0	-10000	0	-10000	0	0
CASP3	-0.034	0.16	-10000	0	-0.42	27	27
E2F1	-0.015	0.12	-10000	0	-0.52	26	26
CASP9	0.013	0.024	-10000	0	-0.5	1	1
IKK complex	-0.071	0.13	-10000	0	-0.52	15	15
NGF (dimer)/TRKA	-0.077	0.17	-10000	0	-0.42	84	84
MMP7	-0.15	0.26	-10000	0	-0.55	136	136
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.082	0.14	-10000	0	-0.54	12	12
MMP3	-0.038	0.15	-10000	0	-0.5	42	42
APAF-1/Caspase 9	-0.072	0.12	-10000	0	-0.45	23	23

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.11	0.16	-9999	-0.36	100	100
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.033	0.046	-9999	-0.25	1	1
AURKB	-0.17	0.27	-9999	-0.56	146	146
AURKC	-0.02	0.13	-9999	-0.52	30	30

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.065	0.2	-9999	-0.59	58	58
PDGF/PDGFRA/CRKL	-0.051	0.14	-9999	-0.41	58	58
positive regulation of JUN kinase activity	-0.041	0.11	-9999	-0.33	47	47
CRKL	0.014	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.063	0.15	-9999	-0.43	67	67
AP1	-0.17	0.32	-9999	-0.9	65	65
mol:IP3	-0.037	0.15	-9999	-0.43	58	58
PLCG1	-0.037	0.15	-9999	-0.43	58	58
PDGF/PDGFRA/alphaV Integrin	-0.052	0.14	-9999	-0.42	58	58
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.037	0.15	-9999	-0.43	58	58
CAV3	-0.007	0.083	-9999	-0.5	13	13
CAV1	-0.048	0.17	-9999	-0.5	56	56
SHC/Grb2/SOS1	-0.041	0.11	-9999	-0.34	47	47
PDGF/PDGFRA/Shf	-0.055	0.15	-9999	-0.43	59	59
FOS	-0.13	0.34	-9999	-0.89	65	65
JUN	-0.02	0.062	-9999	-0.41	10	10
oligodendrocyte development	-0.052	0.14	-9999	-0.42	58	58
GRB2	0.013	0.024	-9999	-0.5	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
mol:DAG	-0.037	0.15	-9999	-0.43	58	58
PDGF/PDGFRA	-0.065	0.2	-9999	-0.59	58	58
actin cytoskeleton reorganization	-0.051	0.14	-9999	-0.41	58	58
SRF	0.028	0.01	-9999	-10000	0	0
SHC1	0.009	0.053	-9999	-0.5	5	5
PI3K	-0.043	0.11	-9999	-0.34	58	58
PDGF/PDGFRA/Crk/C3G	-0.043	0.11	-9999	-0.34	58	58
JAK1	-0.032	0.14	-9999	-0.41	58	58
ELK1/SRF	-0.002	0.11	-9999	-0.32	47	47
SHB	0.014	0	-9999	-10000	0	0
SHF	0.009	0.057	-9999	-0.61	4	4
CSNK2A1	0.014	0.022	-9999	-10000	0	0
GO:0007205	-0.039	0.16	-9999	-0.44	58	58
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.041	0.11	-9999	-0.33	47	47
PDGF/PDGFRA/SHB	-0.051	0.14	-9999	-0.41	58	58
PDGF/PDGFRA/Caveolin-1	-0.094	0.18	-9999	-0.41	105	105
ITGAV	0.013	0.029	-9999	-0.61	1	1
ELK1	-0.029	0.14	-9999	-0.4	51	51
PIK3CA	0.014	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.051	0.14	-9999	-0.41	58	58
JAK-STAT cascade	-0.031	0.14	-9999	-0.41	58	58
cell proliferation	-0.055	0.15	-9999	-0.43	59	59

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.021	0.083	-9999	-0.35	28	28
ARNO/beta Arrestin1-2	-0.024	0.088	-9999	-0.55	7	7
EGFR	-0.083	0.22	-9999	-0.56	79	79
EPHA2	-0.019	0.13	-9999	-0.5	30	30
USP6	0.006	0.066	-9999	-0.5	8	8
IQSEC1	0.005	0.07	-9999	-0.52	8	8
EGFR/EGFR/EGF/EGF	-0.11	0.2	-9999	-0.44	115	115
ARRB2	0.01	0.035	-9999	-10000	0	0
mol:GTP	0.005	0.046	-9999	-0.17	21	21
ARRB1	-0.002	0.099	-9999	-0.61	12	12
FBXO8	0.013	0.029	-9999	-0.61	1	1
TSHR	-0.21	0.28	-9999	-0.55	182	182
EGF	-0.047	0.18	-9999	-0.56	49	49
somatostatin receptor activity	0	0	-9999	-0.001	69	69
ARAP2	-0.004	0.11	-9999	-0.61	14	14
mol:GDP	-0.073	0.12	-9999	-0.29	78	78
mol:PI-3-4-5-P3	0	0	-9999	-0.001	32	32
ITGA2B	-0.046	0.18	-9999	-0.58	47	47
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.019	0.069	-9999	-0.41	3	3
ADAP1	-0.021	0.14	-9999	-0.57	28	28
KIF13B	0.014	0	-9999	-10000	0	0
HGF/MET	-0.17	0.23	-9999	-0.44	177	177
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.065	0.12	-9999	-0.29	62	62
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.096	0.17	-9999	-0.37	120	120
ADRB2	-0.019	0.14	-9999	-0.6	25	25
receptor agonist activity	0	0	-9999	0	72	72
actin filament binding	0	0	-9999	-0.001	73	73
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.055	0.18	-9999	-0.52	60	60
GNAQ	0.014	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	51	51
ARF6/GDP	-0.006	0.1	-9999	-0.38	16	16
ARF6/GDP/GULP/ACAP1	-0.11	0.17	-9999	-0.42	76	76
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.066	0.14	-9999	-0.37	51	51
ACAP1	-0.032	0.15	-9999	-0.51	41	41
ACAP2	0.013	0.029	-9999	-0.61	1	1
LHCGR/beta Arrestin2	0.003	0.048	-9999	-0.29	12	12
EFNA1	0.011	0.041	-9999	-0.5	3	3
HGF	-0.078	0.2	-9999	-0.52	80	80
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.013	0.029	-9999	-0.61	1	1
fibronectin binding	0	0	-9999	0	59	59
endosomal lumen acidification	0	0	-9999	0	73	73
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.053	0.19	-9999	-0.58	52	52
GNAQ/ARNO	0.014	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	37	37
MET	-0.14	0.25	-9999	-0.55	129	129
GNA14	-0.018	0.13	-9999	-0.58	25	25
GNA15	-0.01	0.12	-9999	-0.58	19	19
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	53	53
GNA11	0.005	0.076	-9999	-0.61	7	7
LHCGR	-0.004	0.08	-9999	-0.5	12	12
AGTR1	-0.038	0.16	-9999	-0.56	42	42
desensitization of G-protein coupled receptor protein signaling pathway	0.003	0.048	-9999	-0.29	12	12
IPCEF1/ARNO	-0.058	0.14	-9999	-0.49	14	14
alphaIIb/beta3 Integrin	-0.089	0.18	-9999	-0.42	98	98

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.001	0.023	-9999	-0.35	2	2
PRKCZ	-0.017	0.13	-9999	-0.57	25	25
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0.024	-9999	-0.5	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.08	0.12	-9999	-0.42	25	25
IRAK/TOLLIP	0.031	0.019	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
IKBKG	0.014	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.17	0.22	-9999	-0.42	188	188
IL1A	-0.098	0.23	-9999	-0.55	92	92
IL1B	-0.14	0.22	-9999	-0.41	172	172
IRAK/TRAF6/p62/Atypical PKCs	-0.014	0.059	-9999	-0.43	1	1
IL1R2	-0.13	0.24	-9999	-0.54	116	116
IL1R1	-0.035	0.16	-9999	-0.54	41	41
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.048	0.12	-9999	-0.45	17	17
TOLLIP	0.014	0	-9999	-10000	0	0
TICAM2	0.001	0.089	-9999	-0.6	10	10
MAP3K3	0.014	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.065	0.033	-9999	-10000	0	0
JUN	0.036	0.067	-9999	-0.48	3	3
MAP3K7	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.14	0.18	-9999	-0.56	41	41
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.11	0.17	-9999	-0.39	83	83
PIK3R1	0.014	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.1	0.16	-9999	-0.36	83	83
IL1 beta fragment/IL1R1/IL1RAP	-0.14	0.22	-9999	-0.43	114	114
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.035	0.056	-9999	-0.56	1	1
IRAK1	0.025	0.021	-9999	-0.28	2	2
IL1RN/IL1R1	-0.12	0.2	-9999	-0.41	134	134
IRAK4	0.013	0.024	-9999	-0.5	1	1
PRKCI	0.014	0	-9999	-10000	0	0
TRAF6	0.013	0.029	-9999	-0.61	1	1
PI3K	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.067	0.15	-9999	-0.44	31	31
CHUK	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.14	0.22	-9999	-0.43	114	114
IL1 beta/IL1R2	-0.19	0.23	-9999	-0.39	241	241
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.019	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.16	-9999	-0.5	41	41
IRAK3	0.008	0.062	-9999	-0.58	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.15	0.18	-9999	-0.56	48	48
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.046	0.14	-9999	-0.38	24	24
IL1 alpha/IL1R1/IL1RAP	-0.12	0.18	-9999	-0.36	157	157
RELA	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.014	0	-9999	-10000	0	0
MYD88	0.008	0.062	-9999	-0.58	5	5
IRAK/TRAF6/MEKK3	0.038	0.024	-9999	-0.31	1	1
IL1RAP	-0.04	0.16	-9999	-0.52	47	47
UBE2N	0.014	0	-9999	-10000	0	0
IRAK/TRAF6	-0.12	0.15	-9999	-0.46	48	48
CASP1	-0.017	0.13	-9999	-0.54	26	26
IL1RN/IL1R2	-0.18	0.24	-9999	-0.46	179	179
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.13	0.21	-9999	-0.41	116	116
TMEM189-UBE2V1	0.006	0.034	-9999	-0.5	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.026	0.13	-9999	-0.39	23	23
PIK3CA	0.014	0	-9999	-10000	0	0
IL1RN	-0.11	0.23	-9999	-0.54	106	106
TRAF6/TAK1/TAB1/TAB2	-0.002	0.02	-9999	-0.3	1	1
MAP2K6	0.035	0.027	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.097	0.22	-9999	-0.5	75	75
MAP3K8	-0.008	0.1	-9999	-0.51	18	18
FOS	-0.087	0.2	-9999	-0.49	73	73
PRKCA	0.011	0.029	-9999	-0.61	1	1
PTPN7	-0.13	0.25	-9999	-0.55	114	114
HRAS	0.014	0.001	-9999	-10000	0	0
PRKCB	-0.066	0.19	-9999	-0.53	67	67
NRAS	0.014	0.001	-9999	-10000	0	0
RAS family/GTP	0.021	0.019	-9999	-10000	0	0
MAPK3	-0.071	0.17	-9999	-0.46	66	66
MAP2K1	-0.017	0.14	-9999	-0.49	23	23
ELK1	0.013	0.007	-9999	-10000	0	0
BRAF	-0.054	0.14	-9999	-0.45	37	37
mol:GTP	-0.001	0.002	-9999	-0.005	84	84
MAPK1	-0.071	0.17	-9999	-0.46	66	66
RAF1	-0.039	0.11	-9999	-0.46	22	22
KRAS	0.013	0.024	-9999	-0.5	1	1

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.022	0.1	-10000	0	-0.9	3	3
SMARCC2	0.015	0.011	-10000	0	-10000	0	0
SMARCC1	0.015	0.011	-10000	0	-10000	0	0
TBX21	-0.12	0.25	-10000	0	-0.71	58	58
SUMO2	0.014	0.014	-10000	0	-10000	0	0
STAT1 (dimer)	-0.001	0.11	-10000	0	-0.59	15	15
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	-0.094	0.23	-10000	0	-0.57	86	86
GR alpha/HSP90/FKBP51/HSP90	0.021	0.17	0.29	24	-0.33	40	64
PRL	-0.051	0.098	-10000	0	-0.61	2	2
cortisol/GR alpha (dimer)/TIF2	0.19	0.25	0.52	113	-0.46	3	116
RELA	-0.068	0.098	-10000	0	-0.29	4	4
FGG	0.17	0.17	0.47	51	-0.48	2	53
GR beta/TIF2	0.071	0.16	0.3	41	-0.4	28	69
IFNG	-0.24	0.22	-10000	0	-0.62	66	66
apoptosis	0	0.2	0.62	20	-0.67	1	21
CREB1	0.013	0.024	-10000	0	-10000	0	0
histone acetylation	-0.048	0.13	-10000	0	-0.38	36	36
BGLAP	-0.053	0.13	-10000	0	-0.53	13	13
GR/PKAc	0.091	0.097	0.3	24	-10000	0	24
NF kappa B1 p50/RelA	-0.12	0.18	-10000	0	-0.44	59	59
SMARCD1	0.015	0.011	-10000	0	-10000	0	0
MDM2	0.084	0.08	0.25	43	-10000	0	43
GATA3	-0.1	0.23	-10000	0	-0.54	100	100
AKT1	0.002	0.017	-10000	0	-10000	0	0
CSF2	-0.067	0.1	-10000	0	-0.49	4	4
GSK3B	0.014	0.014	-10000	0	-10000	0	0
NR1I3	0.038	0.19	0.61	18	-0.72	2	20
CSN2	0.15	0.13	0.41	31	-10000	0	31
BRG1/BAF155/BAF170/BAF60A	0.039	0.037	-10000	0	-10000	0	0
NFATC1	-0.015	0.13	-10000	0	-0.58	24	24
POU2F1	0.014	0.03	-10000	0	-0.61	1	1
CDKN1A	-0.069	0.32	-10000	0	-1.4	21	21
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.012	-10000	0	-10000	0	0
SFN	-0.12	0.23	-10000	0	-0.53	109	109
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.044	0.19	0.29	13	-0.43	40	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.036	0.31	0.58	18	-0.82	42	60
JUN	-0.17	0.19	-10000	0	-0.49	72	72
IL4	-0.086	0.15	-10000	0	-0.55	25	25
CDK5R1	-0.02	0.14	-10000	0	-0.6	25	25
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.2	0.2	1	-0.48	109	110
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.03	0.15	0.3	19	-0.33	12	31
cortisol/GR alpha (monomer)	0.25	0.26	0.6	123	-10000	0	123
NCOA2	-0.025	0.15	-10000	0	-0.61	29	29
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.23	-10000	0	-0.6	87	87
AP-1/NFAT1-c-4	-0.32	0.31	-10000	0	-0.68	139	139
AFP	-0.13	0.18	-10000	0	-0.69	11	11
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.12	0.15	0.44	20	-0.47	4	24
TP53	-0.016	0.16	-10000	0	-0.53	32	32
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.45	0.49	-10000	0	-0.99	173	173
KRT14	-0.14	0.18	-10000	0	-0.55	39	39
TBP	0.023	0.019	-10000	0	-10000	0	0
CREBBP	0.033	0.06	-10000	0	-10000	0	0
HDAC1	0.004	0.051	-10000	0	-0.61	3	3
HDAC2	0.014	0.001	-10000	0	-10000	0	0
AP-1	-0.32	0.31	-10000	0	-0.69	140	140
MAPK14	0.013	0.012	-10000	0	-10000	0	0
MAPK10	0.008	0.059	-10000	0	-0.61	4	4
MAPK11	0.008	0.059	-10000	0	-0.6	4	4
KRT5	-0.42	0.46	-10000	0	-0.94	161	161
interleukin-1 receptor activity	0	0.001	-10000	0	-10000	0	0
NCOA1	0.017	0.01	-10000	0	-10000	0	0
STAT1	-0.001	0.11	-10000	0	-0.59	15	15
CGA	-0.073	0.13	-10000	0	-0.52	7	7
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.086	0.11	0.35	20	-10000	0	20
MAPK3	0.013	0.013	-10000	0	-10000	0	0
MAPK1	0.013	0.012	-10000	0	-10000	0	0
ICAM1	-0.21	0.28	-10000	0	-0.74	71	71
NFKB1	-0.068	0.098	-10000	0	-0.31	2	2
MAPK8	-0.14	0.17	-10000	0	-0.48	55	55
MAPK9	0.013	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.003	0.2	0.62	20	-0.71	1	21
BAX	-0.002	0.11	-10000	0	-10000	0	0
POMC	-0.14	0.25	-10000	0	-1.1	18	18
EP300	0.027	0.084	-10000	0	-0.6	4	4
cortisol/GR alpha (dimer)/p53	0.19	0.23	0.51	105	-0.54	2	107
proteasomal ubiquitin-dependent protein catabolic process	0.06	0.07	0.24	24	-10000	0	24
SGK1	0.057	0.24	-10000	0	-1.4	11	11
IL13	-0.24	0.24	-10000	0	-0.67	68	68
IL6	-0.31	0.4	-10000	0	-0.86	132	132
PRKACG	0.005	0.047	-10000	0	-0.5	4	4
IL5	-0.21	0.2	-10000	0	-0.66	26	26
IL2	-0.24	0.22	-10000	0	-0.62	62	62
CDK5	0.014	0.007	-10000	0	-10000	0	0
PRKACB	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.34	0.42	-10000	0	-0.88	144	144
CDK5R1/CDK5	-0.018	0.1	-10000	0	-0.44	25	25
NF kappa B1 p50/RelA/PKAc	-0.061	0.13	-10000	0	-0.42	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.22	0.2	0.49	119	-10000	0	119
SMARCA4	0.015	0.011	-10000	0	-10000	0	0
chromatin remodeling	0.15	0.14	0.37	58	-0.36	1	59
NF kappa B1 p50/RelA/Cbp	-0.058	0.16	-10000	0	-0.51	8	8
JUN (dimer)	-0.17	0.19	-10000	0	-0.49	72	72
YWHAH	-0.01	0.11	-10000	0	-0.5	22	22
VIPR1	-0.13	0.28	-10000	0	-0.74	69	69
NR3C1	0.15	0.15	0.42	70	-10000	0	70
NR4A1	-0.025	0.15	-10000	0	-0.5	39	39
TIF2/SUV420H1	-0.028	0.11	-10000	0	-0.44	29	29
MAPKKK cascade	0	0.2	0.62	20	-0.67	1	21
cortisol/GR alpha (dimer)/Src-1	0.22	0.22	0.51	125	-10000	0	125
PBX1	0.014	0.03	-10000	0	-0.61	1	1
POU1F1	0.004	0.025	-10000	0	-0.5	1	1
SELE	-0.3	0.38	-10000	0	-0.88	105	105
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.14	0.38	57	-0.36	1	58
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.22	0.2	0.49	119	-10000	0	119
mol:cortisol	0.14	0.16	0.33	129	-10000	0	129
MMP1	-0.12	0.16	-10000	0	-0.54	41	41

×

PLK1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.042	0.098	0.2	114	-10000	0	114
BUB1B	-0.062	0.15	-10000	0	-0.31	114	114
PLK1	-0.001	0.044	-10000	0	-0.13	29	29
PLK1S1	0.006	0.023	-10000	0	-0.13	1	1
KIF2A	0.006	0.05	-10000	0	-0.31	5	5
regulation of mitotic centrosome separation	-0.001	0.044	-10000	0	-0.13	29	29
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.14	0.24	-10000	0	-0.44	166	166
WEE1	-0.007	0.089	-10000	0	-0.37	18	18
cytokinesis	-0.11	0.21	-10000	0	-0.42	128	128
PP2A-alpha B56	-0.064	0.23	-10000	0	-0.66	56	56
AURKA	0.001	0.042	-10000	0	-0.16	22	22
PICH/PLK1	-0.031	0.16	-10000	0	-0.43	57	57
CENPE	-0.043	0.14	-10000	0	-0.33	80	80
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.006	0.049	-10000	0	-0.3	5	5
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	-0.021	0.082	-10000	0	-0.2	67	67
PAK1	-0.036	0.15	-10000	0	-0.5	45	45
SPC24	-0.13	0.25	-10000	0	-0.54	122	122
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	-0.036	0.1	-10000	0	-0.23	91	91
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.004	-10000	0	-0.014	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0	0.023	-10000	0	-0.066	28	28
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.011	3	3
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.004	0.011	-10000	0	-10000	0	0
spindle elongation	-0.001	0.044	-10000	0	-0.13	29	29
ODF2	0.013	0.003	-10000	0	-10000	0	0
BUB1	-0.1	0.24	-10000	0	-0.73	56	56
TPT1	0.006	0.023	-10000	0	-0.12	2	2
CDC25C	-0.052	0.14	-10000	0	-0.3	93	93
CDC25B	0.014	0.004	-10000	0	-10000	0	0
SGOL1	-0.042	0.098	-10000	0	-0.2	114	114
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.028	0.089	-10000	0	-0.34	27	27
CDC14B	0.012	0.001	-10000	0	-10000	0	0
CDC20	-0.1	0.23	-10000	0	-0.55	98	98
PLK1/PBIP1	-0.051	0.12	-10000	0	-0.33	66	66
mitosis	0.001	0.005	0.022	7	-0.022	1	8
FBXO5	0.004	0.052	-10000	0	-0.29	8	8
CDC2	0	0.004	-10000	0	-0.014	28	28
NDC80	-0.14	0.25	-10000	0	-0.56	122	122
metaphase plate congression	0.005	0.027	-10000	0	-0.15	2	2
ERCC6L	-0.056	0.14	-10000	0	-0.44	49	49
NLP/gamma Tubulin	0.003	0.025	-10000	0	-0.11	3	3
microtubule cytoskeleton organization	0.006	0.023	-10000	0	-0.12	2	2
G2/M transition DNA damage checkpoint	0	0.002	0.01	4	-10000	0	4
PPP1R12A	0.014	0.001	-10000	0	-10000	0	0
interphase	0	0.002	0.01	4	-10000	0	4
PLK1/PRC1-2	-0.095	0.19	-10000	0	-0.35	154	154
GRASP65/GM130/RAB1/GTP/PLK1	-0.005	0.024	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.037	-10000	0	-0.21	2	2
mitotic prometaphase	-0.001	0.002	-10000	0	-0.01	9	9
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.062	-10000	0	-10000	0	0
microtubule-based process	-0.098	0.17	-10000	0	-0.34	154	154
Golgi organization	-0.001	0.044	-10000	0	-0.13	29	29
Cohesin/SA2	-0.012	0.03	-10000	0	-0.22	2	2
PPP1CB/MYPT1	0.004	0.009	-10000	0	-10000	0	0
KIF20A	-0.18	0.27	-10000	0	-0.56	154	154
APC/C/CDC20	-0.058	0.15	-10000	0	-0.34	98	98
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.05	0.12	-10000	0	-0.33	66	66
PRC1	-0.007	0.1	-10000	0	-0.5	19	19
ECT2	-0.003	0.082	-10000	0	-0.36	20	20
C13orf34	0.006	0.037	-10000	0	-0.21	2	2
NUDC	0.005	0.027	-10000	0	-0.15	2	2
regulation of attachment of spindle microtubules to kinetochore	-0.061	0.15	-10000	0	-0.3	114	114
spindle assembly	0.002	0.036	-10000	0	-0.1	24	24
spindle stabilization	0.006	0.023	-10000	0	-0.13	1	1
APC/C/HCDH1	0.02	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	-0.099	0.17	-10000	0	-0.34	154	154
CCNB1	-0.018	0.12	-10000	0	-0.5	29	29
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	-0.002	0.085	-10000	0	-0.42	16	16
TUBG1	0.006	0.023	-10000	0	-0.13	1	1
G2/M transition of mitotic cell cycle	-0.03	0.087	-10000	0	-0.33	27	27
MLF1IP	-0.047	0.15	-10000	0	-0.41	66	66
INCENP	0.012	0.005	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.037	0.17	-9999	-0.5	26	26
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.16	-9999	-0.5	19	19
alphaV/beta3 Integrin/Osteopontin/Src	-0.067	0.15	-9999	-0.39	80	80
AP1	-0.078	0.23	-9999	-0.6	41	41
ILK	-0.046	0.17	-9999	-0.52	25	25
bone resorption	-0.078	0.24	-9999	-0.55	69	69
PTK2B	-0.011	0.11	-9999	-0.5	23	23
PYK2/p130Cas	-0.096	0.16	-9999	-0.52	41	41
ITGAV	0.016	0.029	-9999	-0.6	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.066	0.16	-9999	-0.42	73	73
alphaV/beta3 Integrin/Osteopontin	-0.095	0.17	-9999	-0.4	90	90
MAP3K1	-0.05	0.18	-9999	-0.5	30	30
JUN	0.003	0.076	-9999	-0.51	10	10
MAPK3	-0.039	0.18	-9999	-0.52	27	27
MAPK1	-0.039	0.18	-9999	-0.52	27	27
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.044	0.18	-9999	-0.5	33	33
ITGB3	-0.053	0.18	-9999	-0.52	60	60
NFKBIA	-0.03	0.18	-9999	-0.5	27	27
FOS	-0.093	0.22	-9999	-0.56	87	87
CD44	-0.061	0.2	-9999	-0.56	60	60
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.07	0.28	-9999	-0.85	33	33
NF kappa B1 p50/RelA	-0.076	0.13	-9999	-0.52	19	19
BCAR1	0.013	0.029	-9999	-0.61	1	1
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.049	0.13	-9999	-0.37	61	61
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.061	0.2	-9999	-0.43	80	80
VAV3	-0.12	0.23	-9999	-0.57	63	63
MAP3K14	-0.048	0.18	-9999	-0.45	41	41
ROCK2	-0.006	0.11	-9999	-0.61	15	15
SPP1	-0.078	0.21	-9999	-0.54	79	79
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.19	-9999	-0.53	62	62
MMP2	-0.066	0.21	-9999	-0.61	31	31

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.04	0.23	-10000	0	-0.7	16	16
CRP	-0.048	0.23	-10000	0	-0.64	25	25
cell cycle arrest	-0.061	0.26	-10000	0	-0.66	41	41
TIMP1	-0.091	0.28	-10000	0	-0.63	62	62
IL6ST	-0.024	0.15	-10000	0	-0.6	28	28
Rac1/GDP	-0.072	0.2	-10000	0	-0.44	76	76
AP1	-0.018	0.14	-10000	0	-0.48	13	13
GAB2	0.014	0.029	-10000	0	-0.61	1	1
TNFSF11	-0.049	0.24	-10000	0	-0.67	23	23
HSP90B1	0.004	0.16	-10000	0	-0.93	12	12
GAB1	0.013	0.037	-10000	0	-0.55	2	2
MAPK14	-0.1	0.24	-10000	0	-0.49	101	101
AKT1	0.06	0.028	-10000	0	-0.46	1	1
FOXO1	0.064	0.036	-10000	0	-0.43	1	1
MAP2K6	-0.091	0.21	0.27	1	-0.42	94	95
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.059	0.22	-10000	0	-0.48	62	62
MITF	-0.071	0.19	0.28	1	-0.42	73	74
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.014	0	-10000	0	-10000	0	0
A2M	0.018	0.076	-10000	0	-1.4	1	1
CEBPB	0.004	0.11	-10000	0	-0.58	15	15
GRB2/SOS1/GAB family/SHP2	0.002	0.081	-10000	0	-0.83	1	1
STAT3	-0.065	0.27	-10000	0	-0.69	43	43
STAT1	-0.008	0.036	-10000	0	-10000	0	0
CEBPD	-0.083	0.33	-10000	0	-0.9	47	47
PIK3CA	0.016	0	-10000	0	-10000	0	0
PI3K	0.025	0.001	-10000	0	-10000	0	0
JUN	0.003	0.076	-10000	0	-0.51	10	10
PIAS3/MITF	-0.06	0.18	-10000	0	-0.41	64	64
MAPK11	-0.11	0.24	-10000	0	-0.49	102	102
STAT3 (dimer)/FOXO1	0.011	0.22	-10000	0	-0.58	16	16
GRB2/SOS1/GAB family	-0.075	0.13	-10000	0	-0.47	29	29
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.069	0.18	-10000	0	-0.41	64	64
GRB2	0.014	0.024	-10000	0	-0.5	1	1
JAK2	0.014	0	-10000	0	-10000	0	0
LBP	-0.038	0.23	-10000	0	-0.62	32	32
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.012	0.009	-10000	0	-10000	0	0
MYC	-0.071	0.31	-10000	0	-0.88	40	40
FGG	-0.049	0.24	-10000	0	-0.67	21	21
macrophage differentiation	-0.061	0.26	-10000	0	-0.66	41	41
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.11	0.18	-10000	0	-0.42	74	74
JUNB	-0.062	0.28	-10000	0	-0.75	39	39
FOS	-0.093	0.22	-10000	0	-0.56	87	87
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.082	0.2	0.3	1	-0.42	80	81
STAT1/PIAS1	-0.059	0.18	0.29	1	-0.43	57	58
GRB2/SOS1/GAB family/SHP2/PI3K	0.046	0.031	-10000	0	-0.49	1	1
STAT3 (dimer)	-0.063	0.27	-10000	0	-0.69	41	41
PRKCD	-0.062	0.26	-10000	0	-0.57	63	63
IL6R	-0.013	0.12	-10000	0	-0.58	20	20
SOCS3	-0.16	0.36	-10000	0	-0.75	93	93
gp130 (dimer)/JAK1/JAK1/LMO4	0.003	0.097	-10000	0	-0.36	28	28
Rac1/GTP	-0.075	0.21	-10000	0	-0.45	75	75
HCK	-0.01	0.11	-10000	0	-0.55	20	20
MAPKKK cascade	0.025	0.07	-10000	0	-0.92	1	1
bone resorption	-0.045	0.23	-10000	0	-0.62	24	24
IRF1	-0.048	0.25	-10000	0	-0.66	30	30
mol:GDP	-0.084	0.21	0.28	1	-0.44	86	87
SOS1	0.015	0.002	-10000	0	-10000	0	0
VAV1	-0.086	0.21	0.28	1	-0.44	86	87
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.23	-10000	0	-0.47	102	102
PTPN11	-0.002	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.11	0.21	-10000	0	-0.43	137	137
gp130 (dimer)/TYK2/TYK2/LMO4	0	0.095	-10000	0	-0.36	28	28
gp130 (dimer)/JAK2/JAK2/LMO4	0	0.095	-10000	0	-0.36	28	28
IL6	-0.14	0.25	-10000	0	-0.55	128	128
PIAS3	0.014	0	-10000	0	-10000	0	0
PTPRE	0.013	0.034	-10000	0	-0.62	1	1
PIAS1	0.009	0.057	-10000	0	-0.61	4	4
RAC1	0.015	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.07	0.16	0.27	1	-0.34	86	87
LMO4	0.013	0.012	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.12	0.21	0.35	1	-0.65	40	41
MCL1	0.065	0.026	-10000	0	-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	-0.051	0.12	-9999	-0.34	47	47
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.091	-9999	-0.46	9	9
AP1	-0.12	0.17	-9999	-0.48	52	52
mol:PIP3	-0.1	0.15	-9999	-0.48	38	38
AKT1	0.018	0.099	-9999	-0.4	2	2
PTK2B	-0.021	0.11	-9999	-0.33	34	34
RHOA	0.007	0.065	-9999	-0.32	7	7
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.002	0.092	-9999	-0.37	10	10
MAGI3	0.002	0.086	-9999	-0.61	9	9
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.043	0.13	-9999	-0.34	52	52
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.11	-9999	-0.34	22	22
NF kappa B1 p50/RelA	-0.071	0.13	-9999	-0.53	19	19
endothelial cell migration	-0.045	0.18	-9999	-0.44	65	65
ADCY4	-0.023	0.15	-9999	-0.42	50	50
ADCY5	-0.029	0.16	-9999	-0.41	59	59
ADCY6	-0.021	0.15	-9999	-0.41	49	49
ADCY7	-0.021	0.15	-9999	-0.41	49	49
ADCY1	-0.05	0.17	-9999	-0.44	58	58
ADCY2	-0.027	0.16	-9999	-0.43	53	53
ADCY3	-0.021	0.15	-9999	-0.41	49	49
ADCY8	-0.046	0.19	-9999	-0.5	55	55
ADCY9	-0.021	0.15	-9999	-0.42	49	49
GSK3B	-0.012	0.11	-9999	-0.34	22	22
arachidonic acid secretion	-0.013	0.14	-9999	-0.38	49	49
GNG2	0.009	0.057	-9999	-0.61	4	4
TRIP6	0.008	0.067	-9999	-0.38	5	5
GNAO1	-0.034	0.14	-9999	-0.35	73	73
HRAS	0.014	0	-9999	-10000	0	0
NFKBIA	-0.013	0.13	-9999	-0.44	20	20
GAB1	0.012	0.037	-9999	-0.55	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.004	0.087	-9999	-1	3	3
JUN	0.003	0.076	-9999	-0.51	10	10
LPA/LPA2/NHERF2	-0.015	0.062	-9999	-0.33	16	16
TIAM1	-0.007	0.11	-9999	-1.3	3	3
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.002	0.093	-9999	-0.38	10	10
PLCB3	0.016	0.061	-9999	-0.29	16	16
FOS	-0.093	0.22	-9999	-0.56	87	87
positive regulation of mitosis	-0.013	0.14	-9999	-0.38	49	49
LPA/LPA1-2-3	-0.083	0.15	-9999	-0.39	58	58
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.013	0.029	-9999	-0.61	1	1
stress fiber formation	-0.024	0.12	-9999	-0.34	34	34
GNAZ	-0.03	0.14	-9999	-0.34	69	69
EGFR/PI3K-beta/Gab1	-0.1	0.16	-9999	-0.5	38	38
positive regulation of dendritic cell cytokine production	-0.083	0.15	-9999	-0.38	58	58
LPA/LPA2/MAGI-3	-0.021	0.08	-9999	-0.37	22	22
ARHGEF1	-0.01	0.12	-9999	-0.56	3	3
GNAI2	-0.03	0.14	-9999	-0.34	68	68
GNAI3	-0.03	0.14	-9999	-0.34	68	68
GNAI1	-0.044	0.15	-9999	-0.35	85	85
LPA/LPA3	-0.04	0.11	-9999	-0.37	46	46
LPA/LPA2	-0.017	0.072	-9999	-0.41	14	14
LPA/LPA1	-0.067	0.15	-9999	-0.38	81	81
HB-EGF/EGFR	-0.14	0.21	-9999	-0.38	185	185
HBEGF	-0.1	0.19	-9999	-0.39	140	140
mol:DAG	0.002	0.093	-9999	-0.38	10	10
cAMP biosynthetic process	-0.025	0.16	-9999	-0.42	49	49
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	-0.018	0.14	-9999	-0.48	19	19
GNAQ	-0.011	0.088	-9999	-0.33	15	15
LPAR2	-0.003	0.099	-9999	-0.56	14	14
LPAR3	-0.043	0.15	-9999	-0.5	46	46
LPAR1	-0.065	0.2	-9999	-0.57	60	60
IL8	-0.19	0.23	-9999	-0.46	160	160
PTK2	-0.048	0.15	-9999	-0.35	58	58
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.043	0.13	-9999	-0.34	52	52
EGFR	-0.084	0.22	-9999	-0.56	79	79
PLCG1	-0.013	0.095	-9999	-0.31	22	22
PLD2	-0.048	0.15	-9999	-0.35	58	58
G12/G13	-0.049	0.11	-9999	-0.34	44	44
PI3K-beta	-0.039	0.086	-9999	-0.39	9	9
cell migration	-0.027	0.056	-9999	-0.24	9	9
SLC9A3R2	0.012	0.033	-9999	-0.5	2	2
PXN	-0.024	0.13	-9999	-0.35	34	34
HRAS/GTP	-0.014	0.15	-9999	-0.39	49	49
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.15	0.25	-9999	-0.53	136	136
PRKCE	0.002	0.082	-9999	-0.52	11	11
PRKCD	-0.006	0.12	-9999	-0.4	21	21
Gi(beta/gamma)	-0.016	0.15	-9999	-0.38	50	50
mol:LPA	-0.004	0.037	-9999	-0.2	8	8
TRIP6/p130 Cas/FAK1/Paxillin	-0.067	0.13	-9999	-0.46	20	20
MAPKKK cascade	-0.013	0.14	-9999	-0.38	49	49
contractile ring contraction involved in cytokinesis	0.007	0.065	-9999	-0.31	7	7
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.028	0.11	-9999	-0.32	34	34
GNA15	-0.024	0.11	-9999	-0.32	32	32
GNA12	0.013	0.029	-9999	-0.6	1	1
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.009	0.11	-9999	-0.36	22	22
GNA11	-0.016	0.099	-9999	-0.35	22	22
Rac1/GTP	-0.004	0.096	-9999	-1.1	3	3
MMP2	-0.046	0.18	-9999	-0.44	65	65

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.017	0.12	-9999	-0.52	27	27
PLK4	-0.012	0.11	-9999	-0.51	23	23
regulation of centriole replication	-0.016	0.12	-9999	-0.37	48	48

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.078	0.18	-10000	0	-0.43	96	96
TP53	-0.035	0.093	0.19	3	-0.44	13	16
Senescence	-0.035	0.092	0.19	3	-0.44	13	16
Apoptosis	-0.035	0.092	0.19	3	-0.44	13	16
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.05	0.1	0.27	70	-0.26	2	72
MDM4	0.004	0.07	-10000	0	-0.5	9	9

×

Nongenotropic Androgen signaling

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
PTK2	0.013	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.062	0.13	-10000	0	-0.32	95	95
regulation of S phase of mitotic cell cycle	-0.017	0.1	-10000	0	-0.26	66	66
GNAO1	0.006	0.07	-10000	0	-0.61	6	6
HRAS	0.014	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.004	0.046	-10000	0	-0.37	7	7
PELP1	0.014	0.001	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.021	0.13	-10000	0	-0.37	21	21
T-DHT/AR	-0.083	0.17	-10000	0	-0.43	91	91
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.006	83	83
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.009	0.12	-10000	0	-0.61	17	17
mol:GDP	-0.076	0.16	-10000	0	-0.46	66	66
cell proliferation	-0.034	0.18	-10000	0	-0.42	55	55
PIK3CA	0.014	0	-10000	0	-10000	0	0
FOS	-0.08	0.28	-10000	0	-0.76	57	57
mol:Ca2+	-0.011	0.02	-10000	0	-0.062	35	35
MAPK3	-0.027	0.15	-10000	0	-0.47	21	21
MAPK1	-0.012	0.09	-10000	0	-0.27	17	17
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.004	87	87
cAMP biosynthetic process	0.005	0.047	-10000	0	-0.34	7	7
GNG2	0.009	0.057	-10000	0	-0.61	4	4
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	87	87
HRAS/GTP	-0.058	0.11	-10000	0	-0.3	72	72
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.014	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	87	87
PI3K	0.001	0.005	-10000	0	-10000	0	0
apoptosis	0.033	0.17	0.42	55	-10000	0	55
T-DHT/AR/PELP1	-0.069	0.14	-10000	0	-0.36	91	91
HRAS/GDP	-0.07	0.15	-10000	0	-0.43	66	66
CREB1	-0.038	0.18	-10000	0	-0.45	55	55
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.1	0.24	-10000	0	-0.58	91	91
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.026	0.13	-10000	0	-0.34	21	21
RAC1-CDC42/GDP	-0.065	0.15	-10000	0	-0.41	66	66
T-DHT/AR/PELP1/Src	-0.061	0.13	-10000	0	-0.32	91	91
MAP2K2	-0.021	0.13	-10000	0	-0.35	21	21
T-DHT/AR/PELP1/Src/PI3K	-0.017	0.11	-10000	0	-0.26	66	66
GNAZ	0.013	0.029	-10000	0	-0.61	1	1
SHBG	0.005	0.074	-10000	0	-0.59	7	7
Gi family/GNB1/GNG2/GDP	0.018	0.083	-10000	0	-0.47	7	7
mol:T-DHT	0	0.001	-10000	0	-0.003	61	61
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	0.003	0.065	-10000	0	-0.41	11	11
Gi family/GTP	-0.015	0.085	-10000	0	-0.36	7	7
CDC42	0.014	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.042	0.14	-10000	0	-0.37	49	49
IKBKB	-0.014	0.079	-10000	0	-0.27	12	12
AKT1	-0.054	0.1	-10000	0	-0.25	43	43
IKBKG	-0.012	0.084	-10000	0	-0.27	19	19
CALM1	-0.057	0.15	-10000	0	-0.41	52	52
PIK3CA	0.014	0	-10000	0	-10000	0	0
MAP3K1	-0.069	0.19	-10000	0	-0.52	48	48
MAP3K7	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.067	0.16	0.21	3	-0.43	53	56
DOK1	0.013	0.029	-10000	0	-0.61	1	1
AP-1	-0.035	0.1	-10000	0	-0.26	32	32
LYN	0.003	0.078	-10000	0	-0.52	10	10
BLNK	-0.055	0.19	-10000	0	-0.59	53	53
SHC1	0.009	0.053	-10000	0	-0.5	5	5
BCR complex	-0.085	0.19	-10000	0	-0.46	87	87
CD22	-0.18	0.22	-10000	0	-0.56	81	81
CAMK2G	-0.046	0.14	-10000	0	-0.47	28	28
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	0.008	0.058	-10000	0	-0.54	5	5
SHC/GRB2/SOS1	-0.096	0.17	-10000	0	-0.56	39	39
GO:0007205	-0.068	0.16	0.21	2	-0.44	53	55
SYK	-0.012	0.12	-10000	0	-0.57	21	21
ELK1	-0.057	0.15	-10000	0	-0.41	52	52
NFATC1	-0.065	0.18	-10000	0	-0.47	54	54
B-cell antigen/BCR complex	-0.085	0.19	-10000	0	-0.46	87	87
PAG1/CSK	-0.001	0.02	-10000	0	-0.44	1	1
NFKBIB	0.006	0.029	-10000	0	-10000	0	0
HRAS	-0.051	0.16	-10000	0	-0.43	45	45
NFKBIA	0.006	0.029	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.012	0.024	-10000	0	-10000	0	0
RasGAP/Csk	-0.14	0.2	-10000	0	-0.56	51	51
mol:GDP	-0.063	0.16	0.22	3	-0.42	53	56
PTEN	0.013	0.029	-10000	0	-0.61	1	1
CD79B	-0.056	0.19	-10000	0	-0.55	58	58
NF-kappa-B/RelA/I kappa B alpha	0.012	0.024	-10000	0	-10000	0	0
GRB2	0.013	0.024	-10000	0	-0.5	1	1
PI3K/BCAP/CD19	-0.094	0.2	-10000	0	-0.5	67	67
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.069	0.17	0.22	3	-0.44	53	56
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.096	0.18	-10000	0	-0.52	41	41
CHUK	-0.012	0.084	-10000	0	-0.28	16	16
IBTK	0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.066	0.14	-10000	0	-0.53	30	30
PTPN6	-0.18	0.22	-10000	0	-0.56	78	78
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	-0.006	0.046	-10000	0	-0.1	32	32
VAV2	-0.12	0.19	-10000	0	-0.59	48	48
ubiquitin-dependent protein catabolic process	0.011	0.028	-10000	0	-10000	0	0
BTK	-0.036	0.19	0.37	1	-1.1	13	14
CD19	-0.12	0.2	-10000	0	-0.57	56	56
MAP4K1	-0.021	0.14	-10000	0	-0.59	27	27
CD72	-0.013	0.12	-10000	0	-0.51	24	24
PAG1	0.013	0.029	-10000	0	-0.61	1	1
MAPK14	-0.051	0.16	-10000	0	-0.44	47	47
SH3BP5	0.008	0.062	-10000	0	-0.58	5	5
PIK3AP1	-0.067	0.19	0.24	3	-0.48	58	61
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.067	0.22	-10000	0	-0.56	55	55
RAF1	-0.04	0.15	-10000	0	-0.46	30	30
RasGAP/p62DOK/SHIP	-0.13	0.19	-10000	0	-0.55	52	52
CD79A	-0.042	0.17	-10000	0	-0.54	47	47
re-entry into mitotic cell cycle	-0.036	0.1	-10000	0	-0.26	31	31
RASA1	0.014	0	-10000	0	-10000	0	0
MAPK3	-0.018	0.13	-10000	0	-0.42	21	21
MAPK1	-0.018	0.13	-10000	0	-0.42	21	21
CD72/SHP1	-0.15	0.23	-10000	0	-0.58	72	72
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.056	0.17	-10000	0	-0.44	49	49
actin cytoskeleton organization	-0.071	0.18	-10000	0	-0.5	47	47
NF-kappa-B/RelA	0.03	0.045	-10000	0	-10000	0	0
Calcineurin	-0.059	0.12	-10000	0	-0.46	26	26
PI3K	-0.14	0.18	-10000	0	-0.49	68	68
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.083	0.18	0.25	3	-0.48	53	56
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.12	0.28	-10000	0	-0.79	57	57
DAPP1	-0.14	0.3	-10000	0	-0.9	52	52
cytokine secretion	-0.06	0.17	-10000	0	-0.44	54	54
mol:DAG	-0.069	0.17	0.22	3	-0.44	53	56
PLCG2	0.001	0.086	-10000	0	-0.55	11	11
MAP2K1	-0.029	0.14	-10000	0	-0.46	23	23
B-cell antigen/BCR complex/FcgammaRIIB	-0.16	0.23	-10000	0	-0.48	131	131
mol:PI-3-4-5-P3	-0.1	0.12	-10000	0	-0.36	55	55
ETS1	-0.038	0.14	-10000	0	-0.44	28	28
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.11	0.2	-10000	0	-0.65	37	37
B-cell antigen/BCR complex/LYN	-0.11	0.2	-10000	0	-0.53	61	61
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.029	-10000	0	-0.61	1	1
RAC1	-0.077	0.19	-10000	0	-0.54	47	47
B-cell antigen/BCR complex/LYN/SYK	-0.18	0.24	-10000	0	-0.61	77	77
CARD11	-0.068	0.19	-10000	0	-0.49	56	56
FCGR2B	-0.15	0.26	-10000	0	-0.55	134	134
PPP3CA	0.012	0.033	-10000	0	-0.5	2	2
BCL10	0.014	0	-10000	0	-10000	0	0
IKK complex	0.001	0.037	-10000	0	-0.12	1	1
PTPRC	-0.042	0.17	-10000	0	-0.54	47	47
PDPK1	-0.054	0.099	-10000	0	-0.25	41	41
PPP3CB	0.011	0.041	-10000	0	-0.5	3	3
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.013	0.024	-10000	0	-0.1	5	5

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.033	0.15	-9999	-0.38	56	56
CRKL	0.014	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.01	0.05	-9999	-0.61	3	3
ITGA4	-0.056	0.19	-9999	-0.54	58	58
alpha4/beta7 Integrin/MAdCAM1	-0.13	0.18	-9999	-0.42	96	96
EPO	-0.009	0.1	-9999	-0.5	19	19
alpha4/beta7 Integrin	-0.081	0.18	-9999	-0.44	86	86
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.05	0.13	-9999	-0.4	58	58
EPO/EPOR (dimer)	-0.016	0.076	-9999	-0.37	20	20
lamellipodium assembly	0.01	0.017	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.002	0.094	-9999	-0.28	32	32
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
MADCAM1	-0.12	0.24	-9999	-0.55	113	113
cell adhesion	-0.13	0.18	-9999	-0.41	96	96
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.012	0.033	-9999	-0.5	2	2
SRC	-0.094	0.18	-9999	-0.36	114	114
ITGB7	-0.034	0.16	-9999	-0.55	40	40
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.13	0.19	-9999	-0.37	167	167
p130Cas/Crk/Dock1	-0.059	0.16	-9999	-0.51	17	17
VCAM1	-0.14	0.26	-9999	-0.57	124	124
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.036	0.098	-9999	-0.34	27	27
BCAR1	-0.079	0.17	-9999	-0.56	16	16
EPOR	0.012	0.033	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0.01	0.018	-9999	-10000	0	0

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.061	0.13	-9999	-0.57	9	9
SMAD6-7/SMURF1	-0.004	0.039	-9999	-0.34	6	6
NOG	-0.066	0.21	-9999	-0.59	61	61
SMAD9	-0.029	0.17	-9999	-0.58	32	32
SMAD4	0.014	0	-9999	-10000	0	0
SMAD5	-0.002	0.12	-9999	-0.48	16	16
BMP7/USAG1	-0.092	0.17	-9999	-0.38	111	111
SMAD5/SKI	0.006	0.12	-9999	-0.46	15	15
SMAD1	0.044	0.031	-9999	-0.32	1	1
BMP2	-0.082	0.22	-9999	-0.61	72	72
SMAD1/SMAD1/SMAD4	-0.004	0.027	-9999	-10000	0	0
BMPR1A	0.014	0	-9999	-10000	0	0
BMPR1B	-0.025	0.15	-9999	-0.61	29	29
BMPR1A-1B/BAMBI	-0.028	0.1	-9999	-0.4	33	33
AHSG	-0.073	0.21	-9999	-0.56	70	70
CER1	-0.015	0.1	-9999	-0.5	20	20
BMP2-4/CER1	-0.086	0.2	-9999	-0.48	84	84
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.016	0.16	-9999	-0.48	34	34
BMP2-4 (homodimer)	-0.087	0.21	-9999	-0.53	76	76
RGMB	0.003	0.079	-9999	-0.56	9	9
BMP6/BMPR2/BMPR1A-1B	-0.029	0.095	-9999	-0.35	32	32
RGMA	-0.002	0.097	-9999	-0.6	12	12
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.023	0.15	-9999	-0.47	34	34
BMP2-4/USAG1	-0.14	0.23	-9999	-0.44	153	153
SMAD6/SMURF1/SMAD5	0.006	0.12	-9999	-0.46	15	15
SOSTDC1	-0.11	0.23	-9999	-0.53	106	106
BMP7/BMPR2/BMPR1A-1B	-0.025	0.086	-9999	-0.33	35	35
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.003	0.096	-9999	-0.52	15	15
HFE2	0.003	0.062	-9999	-0.5	7	7
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.077	0.18	-9999	-0.45	79	79
SMAD5/SMAD5/SMAD4	0.006	0.12	-9999	-0.46	15	15
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.049	0.11	-9999	-0.4	33	33
BMP7 (homodimer)	0.006	0.07	-9999	-0.61	6	6
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.072	0.16	-9999	-0.41	81	81
SMAD1/SKI	0.05	0.029	-9999	-10000	0	0
SMAD6	0.007	0.066	-9999	-0.57	6	6
CTDSP2	0.01	0.047	-9999	-0.5	4	4
BMP2-4/FETUA	-0.12	0.22	-9999	-0.44	131	131
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.17	0.27	-9999	-0.56	150	150
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	-0.006	0.041	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.028	0.11	-9999	-0.44	29	29
CHRDL1	-0.079	0.22	-9999	-0.59	72	72
ENDOFIN/SMAD1	0.05	0.029	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.004	0.031	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	0.005	0.07	-9999	-0.52	8	8
SMURF2	0.012	0.041	-9999	-0.61	2	2
BMP2-4/CHRDL1	-0.13	0.22	-9999	-0.43	138	138
BMP2-4/GREM1	-0.18	0.24	-9999	-0.42	197	197
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.02	0.16	-9999	-0.54	32	32
SMAD1/SMAD6	0.05	0.029	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.006	0.07	-9999	-0.61	6	6
BMP6	-0.003	0.096	-9999	-0.52	15	15
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.016	0.14	-9999	-0.43	34	34
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.049	0.037	-9999	-0.33	1	1
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0.029	-9999	-0.61	1	1
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.003	0.074	-9999	-0.5	10	10
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.054	0.19	-9999	-0.49	50	50
CHRD	0.009	0.057	-9999	-0.61	4	4
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.032	0.17	-9999	-0.51	34	34
BMP4	-0.016	0.13	-9999	-0.6	23	23
FST	-0.067	0.2	-9999	-0.55	67	67
BMP2-4/NOG	-0.12	0.26	-9999	-0.56	98	98
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.023	0.079	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.002	0.17	-9999	-1.3	8	8
VDR	-0.069	0.2	-9999	-0.54	69	69
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.049	0.16	-9999	-0.47	28	28
RXRs/LXRs/DNA/Oxysterols	-0.078	0.22	-9999	-0.46	86	86
MED1	0.014	0	-9999	-10000	0	0
mol:9cRA	-0.009	0.024	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.026	0.059	-9999	-10000	0	0
RXRs/NUR77	-0.038	0.15	-9999	-0.38	57	57
RXRs/PPAR	-0.016	0.12	-9999	-0.37	29	29
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.059	0.14	-9999	-0.4	69	69
RARs/VDR/DNA/Vit D3	-0.043	0.1	-9999	-0.32	33	33
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.069	0.2	-9999	-0.54	69	69
RARs/RARs/DNA/9cRA	0.014	0.037	-9999	-0.31	5	5
RARG	0.013	0.024	-9999	-0.5	1	1
RPS6KB1	0.02	0.067	-9999	-0.4	8	8
RARs/THRs/DNA/SMRT	0.026	0.059	-9999	-0.25	15	15
THRA	0.01	0.05	-9999	-0.61	3	3
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.059	0.14	-9999	-0.4	69	69
RXRs/PPAR/9cRA/PGJ2/DNA	-0.037	0.14	-9999	-0.36	54	54
NR1H4	-0.13	0.24	-9999	-0.54	119	119
RXRs/LXRs/DNA	-0.025	0.15	-9999	-0.45	21	21
NR1H2	0.011	0.017	-9999	-10000	0	0
NR1H3	0.009	0.02	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.061	0.17	-9999	-0.38	79	79
NR4A1	-0.023	0.14	-9999	-0.52	32	32
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.068	0.14	-9999	-0.38	47	47
RXRG	-0.065	0.2	-9999	-0.6	57	57
RXR alpha/CCPG	0.017	0.013	-9999	-10000	0	0
RXRA	0.011	0.017	-9999	-10000	0	0
RXRB	0.009	0.02	-9999	-10000	0	0
THRB	-0.013	0.12	-9999	-0.53	23	23
PPARG	-0.014	0.13	-9999	-0.58	22	22
PPARD	0.014	0	-9999	-10000	0	0
TNF	-0.19	0.42	-9999	-1.1	74	74
mol:Oxysterols	-0.007	0.022	-9999	-10000	0	0
cholesterol transport	-0.077	0.22	-9999	-0.46	86	86
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.009	0.057	-9999	-0.61	4	4
RXRs/NUR77/BCL2	-0.025	0.13	-9999	-0.32	58	58
SREBF1	-0.082	0.27	-9999	-0.92	28	28
RXRs/RXRs/DNA/9cRA	-0.037	0.14	-9999	-0.36	54	54
ABCA1	-0.084	0.28	-9999	-0.89	32	32
RARs/THRs	-0.017	0.066	-9999	-0.3	15	15
RXRs/FXR	-0.097	0.19	-9999	-0.4	97	97
BCL2	0.005	0.076	-9999	-0.61	7	7

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.024	-9999	-0.5	1	1
LAT2	-0.05	0.17	-9999	-0.59	29	29
AP1	-0.1	0.17	-9999	-0.56	40	40
mol:PIP3	-0.063	0.2	-9999	-0.57	36	36
IKBKB	-0.03	0.11	-9999	-0.3	27	27
AKT1	-0.032	0.14	-9999	-0.42	17	17
IKBKG	-0.03	0.11	-9999	-0.29	30	30
MS4A2	-0.026	0.12	-9999	-0.5	26	26
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.001	-9999	-10000	0	0
MAP3K1	-0.015	0.15	-9999	-0.53	25	25
mol:Ca2+	-0.043	0.15	-9999	-0.41	36	36
LYN	0.002	0.079	-9999	-0.53	10	10
CBLB	-0.037	0.13	-9999	-0.49	21	21
SHC1	0.009	0.053	-9999	-0.5	5	5
RasGAP/p62DOK	-0.019	0.072	-9999	-0.29	30	30
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.008	0.058	-9999	-0.54	5	5
PLD2	-0.069	0.16	-9999	-0.35	70	70
PTPN13	-0.028	0.14	-9999	-0.55	17	17
PTPN11	0.011	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.001	0.12	-9999	-0.33	15	15
SYK	-0.014	0.13	-9999	-0.59	21	21
GRB2	0.013	0.024	-9999	-0.5	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.17	-9999	-0.57	36	36
LAT	-0.054	0.15	-9999	-0.41	45	45
PAK2	-0.025	0.17	-9999	-0.6	26	26
NFATC2	-0.097	0.18	-9999	-0.54	55	55
HRAS	-0.037	0.19	-9999	-0.66	28	28
GAB2	0.013	0.029	-9999	-0.61	1	1
PLA2G1B	0.041	0.023	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.18	-9999	-0.36	161	161
Antigen/IgE/Fc epsilon R1	-0.11	0.17	-9999	-0.34	133	133
mol:GDP	-0.046	0.2	-9999	-0.7	29	29
JUN	0.003	0.076	-9999	-0.51	10	10
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.001	-9999	-10000	0	0
FOS	-0.093	0.22	-9999	-0.56	87	87
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.062	0.13	-9999	-0.46	27	27
CHUK	-0.03	0.11	-9999	-0.3	28	28
KLRG1	-0.041	0.13	-9999	-0.5	19	19
VAV1	-0.053	0.18	-9999	-0.62	30	30
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.035	0.13	-9999	-0.51	19	19
negative regulation of mast cell degranulation	-0.032	0.14	-9999	-0.51	20	20
BTK	-0.069	0.19	-9999	-0.74	25	25
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.19	-9999	-0.54	44	44
GAB2/PI3K/SHP2	-0.08	0.12	-9999	-0.47	17	17
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.054	0.15	-9999	-0.53	24	24
RAF1	0.03	0.026	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.18	0.22	-9999	-0.49	107	107
FCER1G	-0.021	0.14	-9999	-0.58	27	27
FCER1A	-0.14	0.25	-9999	-0.54	127	127
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.15	-9999	-0.36	78	78
MAPK3	0.039	0.023	-9999	-10000	0	0
MAPK1	0.039	0.023	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0	0.1	-9999	-0.59	10	10
DUSP1	-0.02	0.14	-9999	-0.54	29	29
NF-kappa-B/RelA	-0.033	0.049	-9999	-0.23	1	1
actin cytoskeleton reorganization	-0.033	0.13	-9999	-0.53	16	16
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.067	0.16	-9999	-0.63	26	26
FER	-0.048	0.15	-9999	-0.44	36	36
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.069	0.12	-9999	-0.35	56	56
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.044	0.2	-9999	-0.69	29	29
cytokine secretion	-0.024	0.036	-9999	-10000	0	0
SPHK1	-0.057	0.16	-9999	-0.47	37	37
PTK2	-0.035	0.14	-9999	-0.55	16	16
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.18	-9999	-0.66	31	31
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.05	0.19	-9999	-0.57	29	29
MAP2K2	0.036	0.023	-9999	-10000	0	0
MAP2K1	0.035	0.026	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.047	0.12	-9999	-0.48	19	19
MAP2K4	0.02	0.014	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.19	0.23	-9999	-0.47	147	147
mol:Choline	-0.068	0.16	-9999	-0.34	70	70
SHC/Grb2/SOS1	-0.057	0.11	-9999	-0.51	17	17
FYN	0.014	0	-9999	-10000	0	0
DOK1	0.013	0.029	-9999	-0.61	1	1
PXN	-0.024	0.13	-9999	-0.5	16	16
HCLS1	-0.053	0.17	-9999	-0.55	32	32
PRKCB	-0.053	0.14	-9999	-0.38	42	42
FCGR2B	-0.15	0.26	-9999	-0.55	134	134
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.033	0.14	-9999	-0.52	20	20
LCP2	-0.004	0.095	-9999	-0.5	16	16
PLA2G4A	-0.052	0.16	-9999	-0.46	38	38
RASA1	0.014	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.068	0.16	-9999	-0.34	70	70
IKK complex	-0.008	0.086	-9999	-0.23	17	17
WIPF1	0.014	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0.05	-10000	0	-0.61	3	3
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	-0.069	0.2	-10000	0	-0.54	69	69
Cbp/p300/PCAF	-0.004	0.036	-10000	0	-0.35	5	5
EP300	0.009	0.057	-10000	0	-0.61	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.016	0.066	-10000	0	-0.4	5	5
KAT2B	0.013	0.024	-10000	0	-0.5	1	1
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.009	0.072	0.23	7	-0.32	4	11
RAR alpha/9cRA/Cyclin H	-0.051	0.085	-10000	0	-0.92	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.013	0.06	-10000	0	-0.34	5	5
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.062	0.1	-10000	0	-0.55	10	10
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.059	0.14	-10000	0	-0.4	69	69
RXRs/RARs/NRIP1/9cRA	-0.058	0.2	-10000	0	-0.47	64	64
NCOA2	-0.025	0.15	-10000	0	-0.61	29	29
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.069	0.2	-10000	0	-0.54	69	69
RARG	0.014	0.024	-10000	0	-0.49	1	1
RAR gamma1/9cRA	-0.001	0.014	-10000	0	-0.29	1	1
MAPK3	0.015	0	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.002	0.09	-10000	0	-0.61	10	10
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.15	0.22	-10000	0	-0.57	81	81
RARA	-0.05	0.12	-10000	0	-0.26	85	85
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.003	0.1	-10000	0	-0.39	16	16
PRKCA	0.016	0.029	-10000	0	-0.61	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.071	0.2	-10000	0	-0.47	76	76
RXRG	-0.12	0.22	-10000	0	-0.46	105	105
RXRA	-0.034	0.11	-10000	0	-0.85	1	1
RXRB	-0.075	0.15	-10000	0	-0.35	76	76
VDR/Vit D3/DNA	-0.059	0.14	-10000	0	-0.4	69	69
RBP1	-0.076	0.2	-10000	0	-0.51	80	80
CRBP1/9-cic-RA	-0.063	0.14	-10000	0	-0.37	80	80
RARB	0.011	0.058	-10000	0	-0.61	4	4
PRKCG	-0.19	0.27	-10000	0	-0.54	171	171
MNAT1	0.013	0.024	-10000	0	-0.5	1	1
RAR alpha/RXRs	-0.061	0.21	-10000	0	-0.51	64	64
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.045	0.17	-10000	0	-0.4	64	64
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.097	-10000	0	-0.41	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.071	0.2	-10000	0	-0.47	76	76
positive regulation of DNA binding	-0.049	0.08	-10000	0	-0.82	1	1
NRIP1	-0.062	0.18	-10000	0	-0.59	24	24
RXRs/RARs	-0.078	0.2	-10000	0	-0.48	76	76
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-10000	0	-0.53	76	76
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	-0.001	0.013	-10000	0	-0.28	1	1
RAR alpha/9cRA	-0.036	0.064	-10000	0	-0.81	1	1
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.001	0.013	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.018	0.006	-9999	-10000	0	0
RAS family/GTP	-0.072	0.16	-9999	-0.54	23	23
NFATC4	-0.062	0.14	-9999	-0.38	30	30
ERBB2IP	0.015	0.029	-9999	-0.6	1	1
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.092	0.16	-9999	-0.49	23	23
JUN	-0.022	0.1	-9999	-0.37	19	19
HRAS	0.014	0.001	-9999	-10000	0	0
DOCK7	-0.086	0.16	-9999	-0.48	27	27
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.14	0.18	-9999	-0.38	127	127
AKT1	0.011	0.004	-9999	-10000	0	0
BAD	0.02	0.003	-9999	-10000	0	0
MAPK10	-0.049	0.077	-9999	-0.24	26	26
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.097	0.17	-9999	-0.53	23	23
RAF1	-0.064	0.16	-9999	-0.52	23	23
ErbB2/ErbB3/neuregulin 2	-0.047	0.12	-9999	-0.36	51	51
STAT3	0.004	0.005	-9999	-10000	0	0
cell migration	-0.021	0.095	-9999	-0.24	19	19
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.15	0.27	-9999	-0.61	85	85
FOS	-0.12	0.22	-9999	-0.42	128	128
NRAS	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.092	0.16	-9999	-0.49	23	23
MAPK3	-0.12	0.23	-9999	-0.51	75	75
MAPK1	-0.12	0.23	-9999	-0.51	75	75
JAK2	-0.082	0.15	-9999	-0.46	23	23
NF2	-0.003	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.094	0.18	-9999	-0.34	126	126
NRG1	-0.17	0.27	-9999	-0.57	146	146
GRB2/SOS1	-0.001	0.016	-9999	-0.35	1	1
MAPK8	-0.077	0.15	-9999	-0.41	27	27
MAPK9	-0.047	0.074	-9999	-0.23	25	25
ERBB2	-0.006	0.045	-9999	-0.37	7	7
ERBB3	-0.063	0.2	-9999	-0.58	58	58
SHC1	0.008	0.053	-9999	-0.5	5	5
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.001	0.011	-9999	-10000	0	0
STAT3 (dimer)	0.01	0.009	-9999	-10000	0	0
RNF41	0.023	0.009	-9999	-10000	0	0
FRAP1	0.009	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.074	0.1	-9999	-0.33	25	25
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.037	-9999	-0.3	7	7
CHRNA1	-0.14	0.26	-9999	-0.58	92	92
myelination	-0.054	0.13	-9999	-0.36	29	29
PPP3CB	-0.077	0.14	-9999	-0.42	25	25
KRAS	0.013	0.024	-9999	-0.5	1	1
RAC1-CDC42/GDP	-0.067	0.16	-9999	-0.54	24	24
NRG2	0.012	0.041	-9999	-0.61	2	2
mol:GDP	-0.093	0.18	-9999	-0.34	126	126
SOS1	0.014	0.001	-9999	-10000	0	0
MAP2K2	-0.062	0.16	-9999	-0.55	17	17
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.081	0.15	-9999	-0.46	23	23
MAP2K1	-0.13	0.22	-9999	-0.52	64	64
heart morphogenesis	-0.092	0.16	-9999	-0.49	23	23
RAS family/GDP	-0.07	0.16	-9999	-0.54	23	23
GRB2	0.013	0.024	-9999	-0.5	1	1
PRKACA	-0.007	0.009	-9999	-10000	0	0
CHRNE	0.001	0.046	-9999	-0.19	21	21
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.011	0.004	-9999	-10000	0	0
nervous system development	-0.092	0.16	-9999	-0.49	23	23
CDC42	0.014	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.014	0.004	-9999	-10000	0	0
SVIL	-0.01	0.11	-9999	-0.5	21	21
ZNF318	0.018	0.017	-9999	-10000	0	0
JMJD2C	-0.002	0.02	-9999	-0.077	27	27
T-DHT/AR/Ubc9	-0.066	0.16	-9999	-0.38	91	91
CARM1	0.014	0.001	-9999	-10000	0	0
PRDX1	-0.014	0.13	-9999	-0.61	21	21
PELP1	0.015	0.003	-9999	-10000	0	0
CTNNB1	0.014	0.004	-9999	-10000	0	0
AKT1	0.015	0.004	-9999	-10000	0	0
PTK2B	-0.012	0.11	-9999	-0.5	23	23
MED1	0.015	0.005	-9999	-10000	0	0
MAK	-0.037	0.16	-9999	-0.5	49	49
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	-0.001	0.095	-9999	-0.61	11	11
GSN	0.002	0.083	-9999	-0.58	9	9
NCOA2	-0.025	0.15	-9999	-0.61	29	29
NCOA6	0.014	0.004	-9999	-10000	0	0
DNA-PK	0.007	0.024	-9999	-10000	0	0
NCOA4	0.014	0.001	-9999	-10000	0	0
PIAS3	0.014	0.004	-9999	-10000	0	0
cell proliferation	-0.043	0.1	-9999	-0.36	26	26
XRCC5	0.015	0.004	-9999	-10000	0	0
UBE3A	0.012	0.009	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.078	0.18	-9999	-0.39	102	102
FHL2	-0.05	0.22	-9999	-0.68	38	38
RANBP9	0.014	0.004	-9999	-10000	0	0
JMJD1A	-0.01	0.055	-9999	-0.11	95	95
CDK6	-0.035	0.16	-9999	-0.54	41	41
TGFB1I1	0.004	0.074	-9999	-0.55	8	8
T-DHT/AR/CyclinD1	-0.086	0.19	-9999	-0.4	106	106
XRCC6	0.015	0.004	-9999	-10000	0	0
T-DHT/AR	-0.074	0.18	-9999	-0.39	99	99
CTDSP1	0.013	0.004	-9999	-10000	0	0
CTDSP2	0.012	0.049	-9999	-0.5	4	4
BRCA1	0.009	0.047	-9999	-0.5	4	4
TCF4	0.015	0.03	-9999	-0.61	1	1
CDKN2A	-0.11	0.24	-9999	-0.57	96	96
SRF	0.017	0.028	-9999	-10000	0	0
NKX3-1	-0.062	0.18	-9999	-0.9	14	14
KLK3	-0.014	0.11	-9999	-10000	0	0
TMF1	0.014	0.003	-9999	-10000	0	0
HNRNPA1	0.016	0.006	-9999	-10000	0	0
AOF2	-0.002	0.007	-9999	-10000	0	0
APPL1	0.028	0.01	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.076	0.17	-9999	-0.38	103	103
AR	-0.11	0.24	-9999	-0.59	91	91
UBA3	0.013	0.004	-9999	-10000	0	0
PATZ1	0.016	0.006	-9999	-10000	0	0
PAWR	-0.028	0.14	-9999	-0.53	35	35
PRKDC	0.015	0.004	-9999	-10000	0	0
PA2G4	0.016	0.007	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.059	0.15	-9999	-0.34	92	92
RPS6KA3	0.012	0.029	-9999	-0.61	1	1
T-DHT/AR/ARA70	-0.067	0.16	-9999	-0.38	91	91
LATS2	-0.002	0.096	-9999	-0.52	15	15
T-DHT/AR/PRX1	-0.074	0.17	-9999	-0.38	102	102
Cyclin D3/CDK11 p58	0	0.017	-9999	-0.36	1	1
VAV3	-0.12	0.23	-9999	-0.53	113	113
KLK2	-0.062	0.11	-9999	-0.44	28	28
CASP8	-0.003	0.094	-9999	-0.5	16	16
T-DHT/AR/TIF2/CARM1	-0.073	0.18	-9999	-0.39	95	95
TMPRSS2	-0.14	0.32	-9999	-0.89	56	56
CCND1	-0.017	0.13	-9999	-0.54	26	26
PIAS1	0.007	0.058	-9999	-0.61	4	4
mol:T-DHT	-0.011	0.032	-9999	-0.08	54	54
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.011	0.015	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.096	0.19	-9999	-0.39	121	121
CMTM2	-0.008	0.11	-9999	-0.56	18	18
SNURF	-0.005	0.11	-9999	-0.59	15	15
ZMIZ1	0.006	0.027	-9999	-10000	0	0
CCND3	0.013	0.024	-9999	-0.5	1	1
TGIF1	-0.006	0.11	-9999	-0.54	18	18
FKBP4	0.014	0.004	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.009	0.06	0.28	7	-10000	0	7
RFC1	0.009	0.06	0.28	7	-10000	0	7
PRKDC	0.009	0.06	0.23	19	-10000	0	19
RIPK1	0.016	0.004	-10000	0	-10000	0	0
CASP7	-0.005	0.076	0.25	14	-0.33	5	19
FASLG/FAS/FADD/FAF1	-0.011	0.092	0.23	19	-0.32	16	35
MAP2K4	-0.009	0.12	-10000	0	-0.36	15	15
mol:ceramide	-0.008	0.1	-10000	0	-0.39	11	11
GSN	0.002	0.07	0.25	5	-0.34	7	12
FASLG/FAS/FADD/FAF1/Caspase 8	-0.005	0.097	0.21	2	-0.32	18	20
FAS	-0.011	0.11	-10000	0	-0.56	18	18
BID	0.006	0.084	0.3	17	-0.29	16	33
MAP3K1	0.007	0.094	0.22	13	-0.28	12	25
MAP3K7	0.012	0.006	-10000	0	-10000	0	0
RB1	0.008	0.062	0.28	7	-0.37	1	8
CFLAR	0.015	0.023	-10000	0	-0.48	1	1
HGF/MET	-0.15	0.2	-10000	0	-0.38	179	179
ARHGDIB	0.007	0.067	0.23	19	-0.37	3	22
FADD	0.011	0.007	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.07	0.34	7	-0.25	5	12
NFKB1	-0.043	0.07	-10000	0	-10000	0	0
MAPK8	-0.035	0.18	-10000	0	-0.43	54	54
DFFA	0.009	0.06	0.28	7	-10000	0	7
DNA fragmentation during apoptosis	0.009	0.06	0.28	7	-10000	0	7
FAS/FADD/MET	-0.1	0.17	-10000	0	-0.35	138	138
CFLAR/RIP1	0.013	0.018	-10000	0	-0.32	1	1
FAIM3	-0.032	0.16	-10000	0	-0.55	39	39
FAF1	0.01	0.03	-10000	0	-0.61	1	1
PARP1	0.008	0.061	0.23	19	-0.29	1	20
DFFB	0.009	0.06	0.28	7	-10000	0	7
CHUK	-0.036	0.06	-10000	0	-10000	0	0
FASLG	-0.033	0.14	-10000	0	-0.5	35	35
FAS/FADD	0	0.084	-10000	0	-0.41	18	18
HGF	-0.078	0.2	-10000	0	-0.52	80	80
LMNA	0.005	0.065	0.25	7	-0.3	6	13
CASP6	0.006	0.069	0.22	23	-0.36	4	27
CASP10	0.01	0.025	-10000	0	-0.51	1	1
CASP3	0.01	0.071	0.26	23	-0.2	6	29
PTPN13	0.005	0.074	-10000	0	-0.59	7	7
CASP8	0.012	0.11	0.32	34	-0.34	16	50
IL6	-0.16	0.4	-10000	0	-1.2	51	51
MET	-0.14	0.25	-10000	0	-0.55	129	129
ICAD/CAD	0.009	0.056	0.26	7	-10000	0	7
FASLG/FAS/FADD/FAF1/Caspase 10	-0.009	0.1	-10000	0	-0.4	11	11
activation of caspase activity by cytochrome c	0.006	0.084	0.3	17	-0.29	16	33
PAK2	0.009	0.06	0.28	7	-10000	0	7
BCL2	0.005	0.076	-10000	0	-0.61	7	7

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.034	0.14	-9999	-0.43	24	24
FZD6	-0.013	0.12	-9999	-0.5	25	25
WNT6	-0.036	0.16	-9999	-0.54	42	42
WNT4	-0.035	0.16	-9999	-0.53	42	42
FZD3	0.01	0.05	-9999	-0.61	3	3
WNT5A	-0.018	0.13	-9999	-0.58	25	25
WNT11	-0.017	0.13	-9999	-0.56	25	25

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.077	0.27	-10000	0	-0.89	28	28
NCK1/PAK1/Dok-R	-0.094	0.13	-10000	0	-0.41	42	42
NCK1/Dok-R	-0.1	0.3	-10000	0	-1.1	28	28
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.012	0.059	0.21	23	-10000	0	23
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.008	0.053	-10000	0	-0.5	5	5
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.011	0.087	0.25	10	-0.49	7	17
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.095	0.25	-10000	0	-1	27	27
FN1	-0.004	0.096	-10000	0	-0.5	17	17
PLD2	-0.07	0.3	-10000	0	-1.1	27	27
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.18	0.27	-10000	0	-0.54	164	164
ELK1	-0.047	0.27	-10000	0	-1	27	27
GRB7	-0.031	0.14	-10000	0	-0.5	38	38
PAK1	-0.036	0.16	-10000	0	-0.51	45	45
Tie2/Ang1/alpha5/beta1 Integrin	-0.12	0.28	-10000	0	-1	32	32
CDKN1A	-0.1	0.29	-10000	0	-0.71	62	62
ITGA5	-0.013	0.12	-10000	0	-0.51	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.1	0.3	-10000	0	-1.1	28	28
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	-0.052	0.22	-10000	0	-0.65	29	29
PLG	-0.079	0.3	-10000	0	-1.1	27	27
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.069	0.25	-10000	0	-0.88	26	26
GRB2	0.013	0.024	-10000	0	-0.5	1	1
PIK3R1	0.014	0.002	-10000	0	-10000	0	0
ANGPT2	-0.11	0.29	-10000	0	-0.84	46	46
BMX	-0.1	0.3	-10000	0	-1.1	28	28
ANGPT1	-0.12	0.33	-10000	0	-1.1	33	33
tube development	-0.081	0.26	-10000	0	-0.68	49	49
ANGPT4	-0.055	0.18	-10000	0	-0.55	56	56
response to hypoxia	-0.007	0.02	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.17	0.34	-10000	0	-1.3	29	29
alpha5/beta1 Integrin	-0.02	0.085	-10000	0	-0.37	25	25
FGF2	0.011	0.047	-10000	0	-0.57	3	3
STAT5A (dimer)	-0.11	0.31	-10000	0	-0.8	52	52
mol:L-citrulline	-0.052	0.22	-10000	0	-0.65	29	29
AGTR1	-0.038	0.16	-10000	0	-0.56	42	42
MAPK14	-0.077	0.29	-10000	0	-1.1	26	26
Tie2/SHP2	-0.036	0.15	-10000	0	-1.2	6	6
TEK	-0.016	0.18	-10000	0	-1.3	6	6
RPS6KB1	-0.063	0.25	-10000	0	-0.87	26	26
Angiotensin II/AT1	-0.029	0.12	-10000	0	-0.41	42	42
Tie2/Ang1/GRB2	-0.073	0.31	-10000	0	-1.2	27	27
MAPK3	-0.054	0.27	-10000	0	-1	27	27
MAPK1	-0.054	0.27	-10000	0	-1	27	27
Tie2/Ang1/GRB7	-0.096	0.31	-10000	0	-1.2	27	27
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.076	0.3	-10000	0	-1.2	27	27
PI3K	-0.084	0.29	-10000	0	-1.1	26	26
FES	-0.077	0.29	-10000	0	-1.1	26	26
Crk/Dok-R	-0.1	0.3	-10000	0	-1.1	28	28
Tie2/Ang1/ABIN2	-0.073	0.31	-10000	0	-1.2	27	27
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.068	0.25	-10000	0	-0.79	28	28
STAT5A	-0.001	0.093	-10000	0	-0.6	11	11
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.063	0.25	-10000	0	-0.87	26	26
Tie2/Ang2	-0.12	0.34	-10000	0	-0.95	48	48
Tie2/Ang1	-0.085	0.32	-10000	0	-1.2	27	27
FOXO1	-0.076	0.27	-10000	0	-0.77	35	35
ELF1	0.019	0.034	-10000	0	-0.65	1	1
ELF2	-0.074	0.29	-10000	0	-1.1	27	27
mol:Choline	-0.064	0.28	-10000	0	-1.1	27	27
cell migration	-0.053	0.072	-10000	0	-0.23	35	35
FYN	-0.095	0.29	-10000	0	-0.78	48	48
DOK2	-0.074	0.2	-10000	0	-0.54	74	74
negative regulation of cell cycle	-0.089	0.26	-10000	0	-0.63	63	63
ETS1	-0.006	0.094	-10000	0	-0.58	8	8
PXN	-0.043	0.22	-10000	0	-0.71	26	26
ITGB1	0.012	0.033	-10000	0	-0.5	2	2
NOS3	-0.062	0.24	-10000	0	-0.75	28	28
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.17	0.27	-10000	0	-0.57	142	142
MAPKKK cascade	-0.064	0.28	-10000	0	-1.1	27	27
RASA1	0.014	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.078	0.31	-10000	0	-1.2	27	27
NCK1	0.013	0.029	-10000	0	-0.61	1	1
vasculogenesis	-0.045	0.2	-10000	0	-0.58	29	29
mol:Phosphatidic acid	-0.064	0.28	-10000	0	-1.1	27	27
mol:Angiotensin II	-0.001	0.008	-10000	0	-10000	0	0
mol:NADP	-0.052	0.22	-10000	0	-0.65	29	29
Rac1/GTP	-0.11	0.2	-10000	0	-0.81	26	26
MMP2	-0.084	0.3	-10000	0	-1.1	27	27

×

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	-0.036	0.1	-10000	0	-0.33	51	51
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.13	0.2	-10000	0	-0.4	159	159
GNB1/GNG2	-0.003	0.035	-10000	0	-0.38	4	4
GNB1	0.014	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	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.037	0.11	-10000	0	-0.35	49	49
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	0.009	0.027	0.089	49	-10000	0	49
GNAL	-0.051	0.19	-10000	0	-0.6	49	49
GNG2	0.009	0.057	-10000	0	-0.61	4	4
CRH	-0.18	0.27	-10000	0	-0.55	159	159
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.055	-10000	0	-0.37	10	10
MAPK11	0.006	0.035	-10000	0	-0.37	4	4

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.014	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.029	0.04	-10000	0	-0.52	1	1
NT3 (dimer)/TRKC	-0.016	0.081	-10000	0	-0.4	18	18
NT3 (dimer)/TRKB	-0.079	0.16	-10000	0	-0.38	96	96
SHC/Grb2/SOS1/GAB1/PI3K	0.038	0.03	-10000	0	-0.45	1	1
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.08	0.2	-10000	0	-0.51	83	83
PIK3CA	0.014	0	-10000	0	-10000	0	0
DYNLT1	0.012	0.041	-10000	0	-0.61	2	2
NTRK1	-0.008	0.11	-10000	0	-0.53	19	19
NTRK2	-0.021	0.14	-10000	0	-0.61	26	26
NTRK3	0.009	0.057	-10000	0	-0.61	4	4
NT-4/5 (dimer)/TRKB	-0.08	0.16	-10000	0	-0.38	97	97
neuron apoptosis	0.13	0.17	0.42	89	-10000	0	89
SHC 2-3/Grb2	-0.14	0.19	-10000	0	-0.46	89	89
SHC1	0.009	0.053	-10000	0	-0.5	5	5
SHC2	-0.075	0.12	-10000	0	-0.42	29	29
SHC3	-0.17	0.24	-10000	0	-0.56	99	99
STAT3 (dimer)	0.007	0.069	-10000	0	-0.35	11	11
NT3 (dimer)/TRKA	-0.071	0.15	-10000	0	-0.36	92	92
RIN/GDP	-0.037	0.12	-10000	0	-0.27	19	19
GIPC1	0.013	0.024	-10000	0	-0.5	1	1
KRAS	0.013	0.024	-10000	0	-0.5	1	1
DNAJA3	-0.073	0.13	-10000	0	-0.37	44	44
RIN/GTP	-0.16	0.2	-10000	0	-0.41	179	179
CCND1	-0.001	0.15	-10000	0	-0.6	26	26
MAGED1	0.014	0	-10000	0	-10000	0	0
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.012	0.093	-10000	0	-0.5	16	16
SHC/GRB2/SOS1	-0.004	0.032	-10000	0	-0.28	6	6
GRB2	0.013	0.024	-10000	0	-0.5	1	1
NGF (dimer)/TRKA/MATK	-0.12	0.2	-10000	0	-0.45	96	96
TRKA/NEDD4-2	-0.026	0.099	-10000	0	-0.39	31	31
ELMO1	0.001	0.09	-10000	0	-0.61	10	10
RhoG/GTP/ELMO1/DOCK1	-0.011	0.062	-10000	0	-0.38	13	13
NGF	-0.074	0.21	-10000	0	-0.58	69	69
HRAS	0.014	0	-10000	0	-10000	0	0
DOCK1	0.01	0.05	-10000	0	-0.61	3	3
GAB2	0.013	0.029	-10000	0	-0.61	1	1
RIT2	-0.21	0.28	-10000	0	-0.56	179	179
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.012	0.037	-10000	0	-0.55	2	2
DNM1	-0.11	0.23	-10000	0	-0.53	106	106
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.077	0.13	-10000	0	-0.36	54	54
mol:GDP	0.045	0.069	-10000	0	-0.46	2	2
NGF (dimer)	-0.074	0.21	-10000	0	-0.57	69	69
RhoG/GDP	-0.01	0.065	-10000	0	-0.45	10	10
RIT1/GDP	0.041	0.05	-10000	0	-0.29	2	2
TIAM1	0.013	0.029	-10000	0	-0.61	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.077	0.14	-10000	0	-0.33	108	108
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.004	0.036	-10000	0	-0.35	5	5
FRS2 family/SHP2	-0.001	0.022	-10000	0	-0.32	2	2
SHC/GRB2/SOS1/GAB1	-0.004	0.039	-10000	0	-0.58	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	16	16
RAP1/GDP	-0.006	0.024	-10000	0	-0.26	1	1
KIDINS220/CRKL	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.08	0.2	-10000	0	-0.51	83	83
ubiquitin-dependent protein catabolic process	-0.072	0.15	-10000	0	-0.37	91	91
Schwann cell development	-0.021	0.028	-10000	0	-10000	0	0
EHD4	0.009	0.053	-10000	0	-0.5	5	5
FRS2 family/GRB2/SOS1	-0.002	0.022	-10000	0	-0.33	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.044	0.017	-10000	0	-10000	0	0
RAP1B	0.013	0.024	-10000	0	-0.5	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.063	0.12	-10000	0	-0.49	17	17
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	-0.001	0.016	-10000	0	-0.35	1	1
Rap1/GTP	-0.023	0.045	-10000	0	-10000	0	0
STAT3	0.007	0.069	-10000	0	-0.35	11	11
axon guidance	-0.061	0.12	-10000	0	-0.47	17	17
MAPK3	-0.085	0.19	-10000	0	-0.4	96	96
MAPK1	-0.085	0.19	-10000	0	-0.4	96	96
CDC42/GDP	0.041	0.05	-10000	0	-0.29	2	2
NTF3	-0.008	0.092	-10000	0	-0.5	16	16
NTF4	-0.012	0.093	-10000	0	-0.5	16	16
NGF (dimer)/TRKA/FAIM	-0.066	0.14	-10000	0	-0.39	61	61
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.01	0.05	-10000	0	-0.61	3	3
GAB1	0.012	0.037	-10000	0	-0.55	2	2
RASGRF1	-0.12	0.17	-10000	0	-0.39	101	101
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	0.013	0.075	-10000	0	-0.33	19	19
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.013	0.076	-10000	0	-10000	0	0
Rac1/GDP	0.041	0.05	-10000	0	-0.29	2	2
NGF (dimer)/TRKA/GRIT	-0.066	0.14	-10000	0	-0.36	84	84
neuron projection morphogenesis	-0.041	0.14	-10000	0	-0.51	9	9
NGF (dimer)/TRKA/NEDD4-2	-0.073	0.16	-10000	0	-0.37	91	91
MAP2K1	0.038	0.042	-10000	0	-0.55	1	1
NGFR	-0.07	0.2	-10000	0	-0.55	69	69
NGF (dimer)/TRKA/GIPC/GAIP	-0.054	0.14	-10000	0	-0.45	25	25
RAS family/GTP/PI3K	0.034	0.008	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.002	0.02	-10000	0	-0.3	1	1
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.016	-10000	0	-0.35	1	1
PRKCI	0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.017	0.13	-10000	0	-0.57	25	25
MAPKKK cascade	-0.089	0.21	-10000	0	-0.62	59	59
RASA1	0.014	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.015	0.075	-10000	0	-0.38	19	19
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.067	0.13	-10000	0	-0.37	41	41
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.067	0.14	-10000	0	-0.64	8	8
MATK	-0.091	0.22	-10000	0	-0.56	85	85
NEDD4L	-0.001	0.092	-10000	0	-0.54	13	13
RAS family/GDP	-0.005	0.022	-10000	0	-0.26	1	1
NGF (dimer)/TRKA	-0.079	0.14	-10000	0	-0.32	91	91
Rac1/GTP	-0.067	0.098	-10000	0	-0.33	30	30
FRS2 family/SHP2/CRK family	-0.001	0.017	-10000	0	-0.3	1	1

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.007	0.07	-9999	-0.32	20	20
ADCY5	-0.002	0.097	-9999	-0.38	27	27
ADCY6	0.014	0.052	-9999	-0.32	11	11
ADCY7	0.014	0.052	-9999	-0.32	11	11
ADCY1	-0.055	0.16	-9999	-0.36	93	93
ADCY2	0.003	0.086	-9999	-0.36	23	23
ADCY3	0.014	0.052	-9999	-0.32	11	11
ADCY8	-0.035	0.14	-9999	-0.36	68	68
PRKCE	0.003	0.061	-9999	-0.38	11	11
ADCY9	0.012	0.06	-9999	-0.34	12	12
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.01	0.1	-9999	-0.36	21	21

×

Regulation of nuclear SMAD2/3 signaling

Figure S60. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S60. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.009	0.06	-10000	0	-0.6	4	4
HSPA8	0.013	0.029	-10000	0	-0.61	1	1
SMAD3/SMAD4/ER alpha	-0.027	0.11	0.22	3	-0.4	23	26
AKT1	0.008	0.024	-10000	0	-10000	0	0
GSC	-0.16	0.48	-10000	0	-1.4	58	58
NKX2-5	-0.095	0.21	-10000	0	-0.51	93	93
muscle cell differentiation	0.15	0.19	0.48	88	-10000	0	88
SMAD2-3/SMAD4/SP1	-0.005	0.11	-10000	0	-0.43	8	8
SMAD4	-0.016	0.066	-10000	0	-0.34	2	2
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.014	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.021	0.11	-10000	0	-0.34	40	40
SMAD3/SMAD4/VDR	-0.037	0.12	-10000	0	-0.37	22	22
MYC	-0.011	0.14	-10000	0	-0.56	25	25
CDKN2B	-0.13	0.45	-10000	0	-1.4	50	50
AP1	-0.028	0.16	-10000	0	-0.5	26	26
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.045	0.055	-10000	0	-0.4	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.008	0.13	-10000	0	-0.38	26	26
SP3	0.017	0.007	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.017	0.11	-10000	0	-0.58	15	15
SMAD3/SMAD4/GR	-0.009	0.062	-10000	0	-0.36	2	2
GATA3	-0.13	0.24	-10000	0	-0.57	100	100
SKI/SIN3/HDAC complex/NCoR1	0.047	0.031	-10000	0	-10000	0	0
MEF2C/TIF2	-0.078	0.19	-10000	0	-0.52	40	40
endothelial cell migration	0.22	0.48	1.3	72	-10000	0	72
MAX	0.023	0.019	-10000	0	-10000	0	0
RBBP7	0.014	0.002	-10000	0	-10000	0	0
RBBP4	0.014	0.002	-10000	0	-10000	0	0
RUNX2	-0.006	0.1	-10000	0	-0.53	17	17
RUNX3	-0.035	0.16	-10000	0	-0.56	40	40
RUNX1	-0.055	0.18	-10000	0	-0.54	58	58
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.023	0.019	-10000	0	-10000	0	0
VDR	-0.069	0.2	-10000	0	-0.54	69	69
CDKN1A	-0.052	0.29	-10000	0	-1.2	22	22
KAT2B	0.013	0.024	-10000	0	-0.5	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.027	0.12	-10000	0	-0.38	25	25
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.014	0.002	-10000	0	-10000	0	0
SERPINE1	-0.22	0.49	-10000	0	-1.3	69	69
SMAD3/SMAD4/ATF2	-0.025	0.078	-10000	0	-0.4	11	11
SMAD3/SMAD4/ATF3	-0.051	0.12	-10000	0	-0.39	45	45
SAP30	0.013	0.029	-10000	0	-0.61	1	1
Cbp/p300/PIAS3	0.013	0.057	0.21	1	-0.36	4	5
JUN	-0.023	0.16	-10000	0	-0.51	24	24
SMAD3/SMAD4/IRF7	-0.034	0.099	-10000	0	-0.42	18	18
TFE3	0.008	0.029	-10000	0	-10000	0	0
COL1A2	-0.043	0.16	-10000	0	-0.46	51	51
mesenchymal cell differentiation	0.03	0.09	0.4	17	-10000	0	17
DLX1	-0.16	0.26	-10000	0	-0.55	141	141
TCF3	0.012	0.041	-10000	0	-0.61	2	2
FOS	-0.09	0.23	-10000	0	-0.56	87	87
SMAD3/SMAD4/Max	-0.009	0.062	-10000	0	-0.36	2	2
Cbp/p300/SNIP1	0.006	0.04	-10000	0	-0.36	4	4
ZBTB17	0.019	0.019	-10000	0	-10000	0	0
LAMC1	0.001	0.11	-10000	0	-0.5	16	16
TGIF2/HDAC complex/SMAD3/SMAD4	-0.023	0.08	-10000	0	-0.45	9	9
IRF7	-0.012	0.12	-10000	0	-0.53	22	22
ESR1	-0.014	0.13	-10000	0	-0.55	24	24
HNF4A	-0.033	0.14	-10000	0	-0.5	37	37
MEF2C	-0.065	0.18	-10000	0	-0.53	30	30
SMAD2-3/SMAD4	-0.034	0.073	-10000	0	-0.37	6	6
Cbp/p300/Src-1	0.01	0.046	-10000	0	-0.36	4	4
IGHV3OR16-13	-0.015	0.033	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.005	0.074	-10000	0	-0.59	7	7
CREBBP	0.014	0.012	-10000	0	-10000	0	0
SKIL	0.005	0.076	-10000	0	-0.61	7	7
HDAC1	0.01	0.05	-10000	0	-0.61	3	3
HDAC2	0.014	0.002	-10000	0	-10000	0	0
SNIP1	0.014	0.005	-10000	0	-10000	0	0
GCN5L2	-0.001	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.011	0.083	-10000	0	-0.4	5	5
MSG1/HSC70	-0.03	0.12	-10000	0	-0.38	46	46
SMAD2	-0.003	0.047	-10000	0	-10000	0	0
SMAD3	-0.005	0.056	-10000	0	-0.26	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.075	-10000	0	-0.3	13	13
SMAD2/SMAD2/SMAD4	-0.003	0.033	-10000	0	-10000	0	0
NCOR1	0.013	0.029	-10000	0	-0.61	1	1
NCOA2	-0.025	0.15	-10000	0	-0.61	29	29
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.14	0.19	-10000	0	-0.4	160	160
SMAD2-3/SMAD4/SP1/MIZ-1	0.006	0.11	-10000	0	-0.45	6	6
IFNB1	-0.008	0.1	-10000	0	-0.46	9	9
SMAD3/SMAD4/MEF2C	-0.069	0.18	-10000	0	-0.52	31	31
CITED1	-0.039	0.16	-10000	0	-0.53	45	45
SMAD2-3/SMAD4/ARC105	-0.012	0.072	-10000	0	-0.35	4	4
RBL1	-0.008	0.11	-10000	0	-0.58	17	17
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.027	0.19	-10000	0	-0.54	51	51
RUNX1-3/PEBPB2	-0.068	0.15	-10000	0	-0.36	88	88
SMAD7	-0.009	0.14	-10000	0	-0.57	7	7
MYC/MIZ-1	-0.004	0.1	-10000	0	-0.4	24	24
SMAD3/SMAD4	-0.043	0.19	0.3	39	-0.42	60	99
IL10	-0.15	0.29	-10000	0	-0.61	108	108
PIASy/HDAC complex	0.016	0.013	-10000	0	-10000	0	0
PIAS3	0.014	0.007	-10000	0	-10000	0	0
CDK2	-0.001	0.092	-10000	0	-0.54	13	13
IL5	-0.085	0.19	-10000	0	-0.51	40	40
CDK4	0.001	0.086	-10000	0	-0.5	13	13
PIAS4	0.016	0.013	-10000	0	-10000	0	0
ATF3	-0.039	0.16	-10000	0	-0.53	46	46
SMAD3/SMAD4/SP1	-0.017	0.097	-10000	0	-0.42	7	7
FOXG1	-0.019	0.14	-10000	0	-0.6	26	26
FOXO3	0.017	0.032	-10000	0	-10000	0	0
FOXO1	0.014	0.047	-10000	0	-0.42	3	3
FOXO4	0.016	0.04	-10000	0	-0.52	1	1
heart looping	-0.064	0.18	-10000	0	-0.52	30	30
CEBPB	-0.008	0.11	-10000	0	-0.59	15	15
SMAD3/SMAD4/DLX1	-0.12	0.18	-10000	0	-0.39	119	119
MYOD1	-0.18	0.27	-10000	0	-0.56	158	158
SMAD3/SMAD4/HNF4	-0.045	0.1	-10000	0	-0.35	30	30
SMAD3/SMAD4/GATA3	-0.13	0.19	-10000	0	-0.46	82	82
SnoN/SIN3/HDAC complex/NCoR1	0.005	0.076	-10000	0	-0.61	7	7
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.065	0.15	-10000	0	-0.4	53	53
SMAD3/SMAD4/SP1-3	0.011	0.097	-10000	0	-0.46	4	4
MED15	0.014	0	-10000	0	-10000	0	0
SP1	0.005	0.04	-10000	0	-10000	0	0
SIN3B	0.014	0.002	-10000	0	-10000	0	0
SIN3A	0.014	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.074	0.17	-10000	0	-0.43	37	37
ITGB5	0.022	0.1	-10000	0	-0.68	4	4
TGIF/SIN3/HDAC complex/CtBP	0.045	0.042	-10000	0	-0.45	1	1
SMAD3/SMAD4/AR	-0.09	0.16	-10000	0	-0.39	87	87
AR	-0.1	0.24	-10000	0	-0.58	91	91
negative regulation of cell growth	-0.007	0.12	-10000	0	-0.41	21	21
SMAD3/SMAD4/MYOD	-0.14	0.18	-10000	0	-0.38	145	145
E2F5	0.01	0.05	-10000	0	-0.61	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.008	0.1	-10000	0	-0.34	14	14
SMAD2-3/SMAD4/FOXO1-3a-4	-0.009	0.13	-10000	0	-0.37	40	40
TFDP1	0.013	0.029	-10000	0	-0.61	1	1
SMAD3/SMAD4/AP1	-0.028	0.16	-10000	0	-0.52	24	24
SMAD3/SMAD4/RUNX2	-0.03	0.09	-10000	0	-0.4	17	17
TGIF2	0.005	0.074	-10000	0	-0.59	7	7
TGIF1	-0.007	0.11	-10000	0	-0.54	18	18
ATF2	0.002	0.086	-10000	0	-0.61	9	9

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.002	0.092	-9999	-0.32	34	34
EPHB2	0.001	0.083	-9999	-0.53	11	11
Syndecan-2/TACI	-0.008	0.082	-9999	-0.33	26	26
LAMA1	-0.058	0.2	-9999	-0.58	56	56
Syndecan-2/alpha2 ITGB1	-0.027	0.15	-9999	-0.4	48	48
HRAS	0.014	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.013	0.067	-9999	-0.34	18	18
ITGA5	-0.013	0.12	-9999	-0.51	24	24
BAX	0.024	0.081	-9999	-10000	0	0
EPB41	0.011	0.047	-9999	-0.57	3	3
positive regulation of cell-cell adhesion	-0.012	0.059	-9999	-0.3	18	18
LAMA3	-0.041	0.17	-9999	-0.56	45	45
EZR	0.005	0.076	-9999	-0.61	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.014	0.12	-9999	-0.5	25	25
Syndecan-2/MMP2	-0.004	0.1	-9999	-0.34	40	40
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.036	0.12	-9999	-0.39	43	43
dendrite morphogenesis	0.005	0.09	-9999	-0.35	27	27
Syndecan-2/GM-CSF	-0.012	0.067	-9999	-0.34	18	18
determination of left/right symmetry	0.006	0.082	-9999	-0.4	18	18
Syndecan-2/PKC delta	-0.005	0.12	-9999	-0.41	34	34
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	0.014	0.064	-9999	-0.33	11	11
MAPK1	0.014	0.064	-9999	-0.3	18	18
Syndecan-2/RACK1	-0.01	0.054	-9999	-0.31	11	11
NF1	0.012	0.041	-9999	-0.61	2	2
FGFR/FGF/Syndecan-2	0.006	0.082	-9999	-0.4	18	18
ITGA2	-0.036	0.16	-9999	-0.55	41	41
MAPK8	0.015	0.09	-9999	-0.34	28	28
Syndecan-2/alpha2/beta1 Integrin	-0.037	0.17	-9999	-0.38	67	67
Syndecan-2/Kininogen	-0.019	0.091	-9999	-0.31	40	40
ITGB1	0.012	0.033	-9999	-0.5	2	2
SRC	0.029	0.058	-9999	-0.28	11	11
Syndecan-2/CASK/Protein 4.1	-0.013	0.07	-9999	-0.34	19	19
extracellular matrix organization	0.006	0.089	-9999	-0.36	25	25
actin cytoskeleton reorganization	0.002	0.091	-9999	-0.32	34	34
Syndecan-2/Caveolin-2/Ras	0.006	0.093	-9999	-0.29	41	41
Syndecan-2/Laminin alpha3	-0.021	0.13	-9999	-0.36	58	58
Syndecan-2/RasGAP	-0.01	0.05	-9999	-0.29	11	11
alpha5/beta1 Integrin	-0.02	0.085	-9999	-0.37	25	25
PRKCD	-0.015	0.13	-9999	-0.61	22	22
Syndecan-2 dimer	0.005	0.09	-9999	-0.35	27	27
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.037	0.057	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.004	0.069	-9999	-0.5	9	9
RASA1	0.014	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.036	0.12	-9999	-0.39	43	43
Syndecan-2/Synbindin	0.013	0.07	-9999	-0.33	18	18
TGFB1	0.004	0.081	-9999	-0.61	8	8
CASP3	0.006	0.11	-9999	-0.4	27	27
FN1	-0.004	0.096	-9999	-0.5	17	17
Syndecan-2/IL8	-0.099	0.18	-9999	-0.33	162	162
SDC2	0.006	0.083	-9999	-0.4	18	18
KNG1	-0.019	0.11	-9999	-0.5	22	22
Syndecan-2/Neurofibromin	0.012	0.077	-9999	-0.35	19	19
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	0.001	0.003	-9999	-10000	0	0
Syndecan-2/TGFB1	0.006	0.089	-9999	-0.36	25	25
Syndecan-2/Syntenin/PI-4-5-P2	-0.011	0.059	-9999	-0.3	18	18
Syndecan-2/Ezrin	0.017	0.088	-9999	-0.42	14	14
PRKACA	0.022	0.071	-9999	-0.34	13	13
angiogenesis	-0.099	0.18	-9999	-0.33	162	162
MMP2	-0.013	0.12	-9999	-0.54	23	23
IL8	-0.17	0.26	-9999	-0.54	151	151
calcineurin-NFAT signaling pathway	-0.008	0.082	-9999	-0.33	26	26

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.057	0.11	0.51	10	-10000	0	10
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.091	0.15	-10000	0	-0.34	123	123
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.006	0.07	-10000	0	-0.61	6	6
RhoA/GTP	-0.058	0.11	-10000	0	-0.52	10	10
negative regulation of cAMP metabolic process	-0.038	0.14	-10000	0	-0.29	73	73
GNAZ	0.013	0.029	-10000	0	-0.61	1	1
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.013	0.029	-10000	0	-0.61	1	1
S1PR5	-0.14	0.26	-10000	0	-0.56	123	123
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.038	0.14	-10000	0	-0.3	73	73
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.008	0.12	-10000	0	-0.61	17	17

×

IL2 signaling events mediated by STAT5

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
GAB2	0.014	0.029	-9999	-0.61	1	1
ELF1	-0.017	0.095	-9999	-0.37	12	12
CCNA2	-0.058	0.19	-9999	-0.54	61	61
PIK3CA	0.015	0.001	-9999	-10000	0	0
JAK3	-0.059	0.19	-9999	-0.54	62	62
PIK3R1	0.015	0.001	-9999	-10000	0	0
JAK1	0.015	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.03	0.16	-9999	-0.44	27	27
SHC1	0.01	0.053	-9999	-0.5	5	5
SP1	0.016	0.046	-9999	-0.35	4	4
IL2RA	-0.046	0.19	-9999	-0.49	66	66
IL2RB	-0.098	0.22	-9999	-0.54	94	94
SOS1	0.015	0.001	-9999	-10000	0	0
IL2RG	-0.042	0.17	-9999	-0.53	49	49
G1/S transition of mitotic cell cycle	-0.038	0.19	-9999	-0.52	42	42
PTPN11	0.015	0.001	-9999	-10000	0	0
CCND2	0.019	0.099	-9999	-0.56	12	12
LCK	-0.088	0.22	-9999	-0.54	85	85
GRB2	0.014	0.024	-9999	-0.49	1	1
IL2	0.001	0.003	-9999	-10000	0	0
CDK6	-0.035	0.16	-9999	-0.54	41	41
CCND3	-0.016	0.14	-9999	-0.49	5	5

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.062	0.15	0.4	72	-10000	0	72
KIRREL	-0.033	0.16	-10000	0	-0.61	33	33
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.063	0.15	-10000	0	-0.4	72	72
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.045	0.11	-10000	0	-0.34	34	34
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.003	0.094	-10000	0	-0.46	4	4
FYN	-0.023	0.11	-10000	0	-0.33	34	34
mol:Ca2+	-0.045	0.11	-10000	0	-0.34	34	34
mol:DAG	-0.045	0.11	-10000	0	-0.34	34	34
NPHS2	-0.006	0.041	-10000	0	-0.55	2	2
mol:IP3	-0.045	0.11	-10000	0	-0.34	34	34
regulation of endocytosis	-0.017	0.1	-10000	0	-0.37	8	8
Nephrin/NEPH1/podocin/Cholesterol	-0.047	0.11	-10000	0	-0.35	34	34
establishment of cell polarity	-0.062	0.15	-10000	0	-0.4	72	72
Nephrin/NEPH1/podocin/NCK1-2	-0.041	0.099	-10000	0	-0.55	4	4
Nephrin/NEPH1/beta Arrestin2	-0.013	0.1	-10000	0	-0.38	8	8
NPHS1	-0.038	0.15	-10000	0	-0.5	42	42
Nephrin/NEPH1/podocin	-0.027	0.11	-10000	0	-0.33	34	34
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.029	-10000	0	-0.61	1	1
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.045	0.11	-10000	0	-0.34	34	34
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.046	0.11	-10000	0	-0.34	34	34
GRB2	0.013	0.024	-10000	0	-0.5	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.041	0.13	-10000	0	-0.34	47	47
cytoskeleton organization	-0.003	0.11	-10000	0	-0.46	6	6
Nephrin/NEPH1	-0.044	0.11	-10000	0	-0.28	72	72
Nephrin/NEPH1/ZO-1	-0.048	0.12	-10000	0	-0.37	33	33

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.079	0.15	-9999	-0.38	77	77
MAP4K1	-0.021	0.14	-9999	-0.59	27	27
MAP3K8	-0.006	0.1	-9999	-0.51	18	18
PRKCB	-0.065	0.19	-9999	-0.53	67	67
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.014	0	-9999	-10000	0	0
MAP3K1	-0.007	0.11	-9999	-0.45	7	7
JUN	-0.029	0.16	-9999	-0.58	31	31
MAP3K7	-0.004	0.11	-9999	-0.45	7	7
GRAP2	-0.051	0.18	-9999	-0.54	54	54
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0	0.11	-9999	-0.42	10	10
LAT	-0.022	0.14	-9999	-0.6	27	27
LCP2	-0.004	0.094	-9999	-0.5	16	16
MAPK8	-0.033	0.17	-9999	-0.61	30	30
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.014	0.12	-9999	-0.48	7	7
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.073	0.14	-9999	-0.55	16	16

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.008	0.064	-10000	0	-0.61	5	5
ANTXR2	0.001	0.084	-10000	0	-0.51	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.067	17	17
monocyte activation	-0.16	0.26	-10000	0	-0.52	132	132
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.003	0.018	-10000	0	-0.33	1	1
MAP2K7	-0.002	0.01	-10000	0	-10000	0	0
MAP2K6	-0.003	0.018	-10000	0	-0.33	1	1
CYAA	0.006	0.056	-10000	0	-0.28	17	17
MAP2K4	-0.003	0.023	-10000	0	-0.33	2	2
IL1B	-0.085	0.14	-10000	0	-0.28	157	157
Channel	-0.011	0.056	-10000	0	-0.3	17	17
NLRP1	-0.003	0.024	-10000	0	-0.33	2	2
CALM1	0.012	0.037	-10000	0	-0.55	2	2
negative regulation of phagocytosis	-0.004	0.03	-10000	0	-0.55	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.067	17	-10000	0	17
MAPK3	-0.002	0.01	-10000	0	-10000	0	0
MAPK1	-0.002	0.01	-10000	0	-10000	0	0
PGR	-0.032	0.096	-10000	0	-0.34	42	42
PA/Cellular Receptors	-0.012	0.062	-10000	0	-0.33	17	17
apoptosis	-0.002	0.013	-10000	0	-0.067	17	17
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.007	0.055	-10000	0	-0.27	17	17
macrophage activation	0.019	0.012	-10000	0	-10000	0	0
TNF	-0.16	0.26	-10000	0	-0.55	142	142
VCAM1	-0.16	0.26	-10000	0	-0.53	132	132
platelet activation	-0.004	0.03	-10000	0	-0.55	1	1
MAPKKK cascade	-0.015	0.018	0.18	2	-10000	0	2
IL18	-0.009	0.089	-10000	0	-0.3	36	36
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.067	17	17
LEF	-0.002	0.013	-10000	0	-0.067	17	17
CASP1	-0.005	0.024	-10000	0	-0.28	2	2
mol:cAMP	-0.004	0.03	-10000	0	-0.55	1	1
necrosis	-0.002	0.013	-10000	0	-0.067	17	17
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.007	0.056	-10000	0	-0.28	17	17
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.043	0.15	-10000	0	-0.73	15	15
HDAC1	0.009	0.05	-10000	0	-0.6	3	3
AES	0.014	0.004	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	0.002	0.084	-10000	0	-0.6	9	9
LRP6/FZD1	-0.004	0.039	-10000	0	-0.35	6	6
TLE1	0.013	0.029	-10000	0	-0.61	1	1
AP1	-0.026	0.12	-10000	0	-0.29	61	61
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.002	0.086	-10000	0	-0.61	9	9
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.027	0.073	-10000	0	-10000	0	0
NICD/RBPSUH	-0.019	0.11	-10000	0	-0.6	15	15
WIF1	-0.28	0.28	-10000	0	-0.55	244	244
NOTCH1	-0.021	0.11	-10000	0	-0.64	15	15
PSENEN	0.014	0	-10000	0	-10000	0	0
KREMEN2	-0.053	0.18	-10000	0	-0.54	56	56
DKK1	-0.12	0.24	-10000	0	-0.54	109	109
beta catenin/beta TrCP1	0.015	0.043	0.33	2	-10000	0	2
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	0	0.043	0.23	3	-0.23	5	8
CtBP/CBP/TCF1/TLE1/AES	0.032	0.05	0.29	4	-10000	0	4
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.093	0.22	-10000	0	-0.56	87	87
JUN	0.003	0.076	-10000	0	-0.51	10	10
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
CTNNB1	0.008	0.046	0.31	3	-10000	0	3
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.36	143	143
HNF1A	0.013	0.029	-10000	0	-0.61	1	1
CTBP1	0.014	0.004	-10000	0	-10000	0	0
MYC	-0.045	0.3	-10000	0	-1.4	22	22
NKD1	0.001	0.087	-10000	0	-0.56	11	11
FZD1	0.009	0.053	-10000	0	-0.5	5	5
NOTCH1 precursor/Deltex homolog 1	-0.024	0.12	-10000	0	-0.62	15	15
apoptosis	-0.026	0.12	-10000	0	-0.29	61	61
Delta 1/NOTCHprecursor	-0.042	0.15	-10000	0	-0.72	15	15
DLL1	-0.035	0.17	-10000	0	-0.61	37	37
PPARD	0.02	0.027	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.062	0.23	3	-0.35	6	9
DVL1	-0.021	0.025	-10000	0	-10000	0	0
CSNK2A1	0.014	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.42	74	74
LRP6	0.013	0.024	-10000	0	-0.5	1	1
CSNK1A1	0.014	0.004	-10000	0	-10000	0	0
NLK	0.017	0.016	-10000	0	-10000	0	0
CCND1	-0.024	0.23	-10000	0	-1.4	11	11
WNT1	-0.023	0.13	-10000	0	-0.5	31	31
Axin1/APC/beta catenin	0.017	0.061	0.33	3	-0.41	2	5
DKK2	-0.11	0.23	-10000	0	-0.55	103	103
NOTCH1 precursor/DVL1	-0.019	0.1	-10000	0	-0.57	15	15
GSK3B	0.014	0.001	-10000	0	-10000	0	0
FRAT1	0.01	0.047	-10000	0	-0.57	3	3
NOTCH/Deltex homolog 1	-0.025	0.12	-10000	0	-0.63	15	15
PPP2R5D	-0.006	0.043	0.26	11	-10000	0	11
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.17	0.17	-10000	0	-0.38	126	126
RBPJ	0.013	0.024	-10000	0	-0.5	1	1
CREBBP	0.017	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.009	0.057	-10000	0	-0.61	4	4
HDAC4	0.014	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.028	0.039	0.35	3	-10000	0	3
CDKN1A	-0.057	0.18	-10000	0	-0.49	57	57
KAT2B	0.013	0.024	-10000	0	-0.5	1	1
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.004	0.043	0.46	4	-10000	0	4
FOXO1	0.011	0.047	-10000	0	-0.57	3	3
FOXO4	0.022	0.033	-10000	0	-0.3	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	-0.082	0.21	-10000	0	-0.54	80	80
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.12	0.2	-10000	0	-0.4	158	158
PPARGC1A	-0.012	0.12	-10000	0	-0.59	20	20
FHL2	-0.031	0.15	-10000	0	-0.53	38	38
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.013	0.037	-10000	0	-10000	0	0
HIST2H4A	0.028	0.039	-10000	0	-0.35	3	3
SIRT1/FOXO3a	0.014	0.041	0.3	4	-10000	0	4
SIRT1	0.017	0.047	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.012	0.039	-10000	0	-0.28	1	1
SIRT1/Histone H1b	0.002	0.066	-10000	0	-0.26	13	13
apoptosis	-0.013	0.036	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.004	0.083	-10000	0	-0.36	20	20
p53/SIRT1	0.025	0.13	0.4	19	-0.44	12	31
SIRT1/FOXO4	0.012	0.048	-10000	0	-0.25	4	4
FOXO1/FHL2/SIRT1	-0.014	0.09	-10000	0	-0.29	36	36
HIST1H1E	0.008	0.067	-10000	0	-0.31	14	14
SIRT1/p300	0.009	0.056	-10000	0	-0.44	4	4
muscle cell differentiation	0.1	0.17	0.33	157	-10000	0	157
TP53	-0.001	0.11	-10000	0	-0.58	14	14
KU70/SIRT1/BAX	0.013	0.036	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.013	0.024	-10000	0	-0.5	1	1
HIV-1 Tat/SIRT1	-0.056	0.15	-10000	0	-0.38	79	79
ACSS2	0.03	0.025	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.1	0.17	-10000	0	-0.33	157	157

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.081	-10000	0	-0.61	8	8
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.001	0.099	0.45	5	-10000	0	5
IL27/IL27R/JAK1	-0.033	0.15	-10000	0	-0.57	6	6
TBX21	-0.057	0.22	-10000	0	-0.56	39	39
IL12B	0	0.047	-10000	0	-0.5	4	4
IL12A	-0.01	0.098	-10000	0	-0.44	23	23
IL6ST	-0.023	0.15	-10000	0	-0.61	28	28
IL27RA/JAK1	0.019	0.037	-10000	0	-10000	0	0
IL27	-0.017	0.11	-10000	0	-0.49	25	25
TYK2	0.015	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.06	0.12	-10000	0	-0.73	2	2
T-helper 2 cell differentiation	0.001	0.099	0.45	5	-10000	0	5
T cell proliferation during immune response	0.001	0.099	0.45	5	-10000	0	5
MAPKKK cascade	-0.001	0.099	-10000	0	-0.45	5	5
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.01	0.047	-10000	0	-0.5	4	4
STAT1	-0.003	0.091	-10000	0	-0.5	15	15
IL12RB1	-0.031	0.16	-10000	0	-0.56	36	36
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.087	0.24	-10000	0	-0.54	55	55
IL27/IL27R/JAK2/TYK2	-0.001	0.1	-10000	0	-0.45	5	5
positive regulation of T cell mediated cytotoxicity	-0.001	0.099	-10000	0	-0.45	5	5
STAT1 (dimer)	-0.062	0.24	0.52	24	-0.66	16	40
JAK2	0.015	0.004	-10000	0	-10000	0	0
JAK1	0.014	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	0.005	0.099	-10000	0	-0.42	5	5
T cell proliferation	-0.071	0.16	-10000	0	-0.5	16	16
IL12/IL12R/TYK2/JAK2	-0.003	0.091	-10000	0	-0.57	4	4
IL17A	-0.06	0.12	-10000	0	-0.73	2	2
mast cell activation	0.001	0.099	0.45	5	-10000	0	5
IFNG	0.002	0.02	-10000	0	-0.092	3	3
T cell differentiation	-0.004	0.005	-10000	0	-0.022	3	3
STAT3 (dimer)	0.007	0.094	-10000	0	-0.42	5	5
STAT5A (dimer)	-0.001	0.11	-10000	0	-0.48	10	10
STAT4 (dimer)	-0.085	0.17	-10000	0	-0.48	21	21
STAT4	-0.16	0.26	-10000	0	-0.54	148	148
T cell activation	-0.009	0.007	0.062	3	-10000	0	3
IL27R/JAK2/TYK2	-0.009	0.086	-10000	0	-10000	0	0
GATA3	-0.15	0.4	-10000	0	-1.4	43	43
IL18	-0.02	0.11	-10000	0	-0.41	36	36
positive regulation of mast cell cytokine production	0.007	0.093	-10000	0	-0.42	5	5
IL27/EBI3	-0.02	0.12	-10000	0	-0.4	41	41
IL27RA	0.014	0.036	-10000	0	-10000	0	0
IL6	-0.14	0.25	-10000	0	-0.54	128	128
STAT5A	0	0.093	-10000	0	-0.6	11	11
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.001	0.021	-10000	0	-10000	0	0
IL1B	-0.13	0.2	-10000	0	-0.4	157	157
EBI3	-0.012	0.12	-10000	0	-0.58	19	19
TNF	-0.11	0.19	-10000	0	-0.4	142	142

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.041	-10000	0	-0.5	3	3
Jak2/Leptin Receptor	-0.01	0.11	0.2	18	-0.45	12	30
PTP1B/AKT1	-0.006	0.088	-10000	0	-0.35	9	9
FYN	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.015	0.097	-10000	0	-0.3	24	24
EGFR	-0.084	0.22	-10000	0	-0.56	79	79
EGF/EGFR	-0.095	0.16	-10000	0	-0.4	82	82
CSF1	-0.007	0.11	-10000	0	-0.61	16	16
AKT1	0.014	0.002	-10000	0	-10000	0	0
INSR	0.014	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.007	0.095	-10000	0	-0.35	13	13
Insulin Receptor/Insulin	-0.026	0.061	-10000	0	-0.32	8	8
HCK	-0.01	0.11	-10000	0	-0.55	20	20
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.006	0.093	-10000	0	-0.34	11	11
EGF	-0.048	0.18	-10000	0	-0.57	49	49
YES1	0.01	0.05	-10000	0	-0.61	3	3
CAV1	-0.029	0.12	-10000	0	-0.35	32	32
TXN	0.012	0.025	-10000	0	-0.5	1	1
PTP1B/IRS1/GRB2	-0.003	0.089	-10000	0	-0.34	10	10
cell migration	0.015	0.097	0.3	24	-10000	0	24
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	-0.021	0.14	-10000	0	-0.56	30	30
ITGA2B	-0.047	0.18	-10000	0	-0.58	47	47
CSF1R	-0.022	0.14	-10000	0	-0.58	28	28
Prolactin Receptor/Prolactin	-0.019	0.11	-10000	0	-0.41	32	32
FGR	0.011	0.041	-10000	0	-0.5	3	3
PTP1B/p130 Cas	-0.007	0.093	-10000	0	-0.33	14	14
Crk/p130 Cas	-0.003	0.088	-10000	0	-0.35	9	9
DOK1	0.003	0.089	-10000	0	-0.34	10	10
JAK2	0.001	0.089	-10000	0	-0.35	13	13
Jak2/Leptin Receptor/Leptin	-0.12	0.19	-10000	0	-0.43	105	105
PIK3R1	0.014	0	-10000	0	-10000	0	0
PTPN1	-0.015	0.098	-10000	0	-0.3	24	24
LYN	0.003	0.078	-10000	0	-0.52	10	10
CDH2	0.013	0.029	-10000	0	-0.61	1	1
SRC	0.012	0.039	-10000	0	-10000	0	0
ITGB3	-0.056	0.18	-10000	0	-0.52	60	60
CAT1/PTP1B	-0.064	0.15	-10000	0	-0.4	47	47
CAPN1	0.014	0.029	-10000	0	-0.61	1	1
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.019	0.053	-10000	0	-0.36	2	2
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.12	0.19	-10000	0	-0.44	104	104
negative regulation of transcription	0.001	0.088	-10000	0	-0.35	13	13
FCGR2A	-0.032	0.16	-10000	0	-0.55	38	38
FER	-0.011	0.12	-10000	0	-0.62	18	18
alphaIIb/beta3 Integrin	-0.086	0.18	-10000	0	-0.42	98	98
BLK	-0.11	0.22	-10000	0	-0.52	104	104
Insulin Receptor/Insulin/Shc	-0.005	0.045	-10000	0	-0.32	8	8
RHOA	0.015	0.002	-10000	0	-10000	0	0
LEPR	-0.001	0.096	-10000	0	-0.54	14	14
BCAR1	0.013	0.029	-10000	0	-0.61	1	1
p210 bcr-abl/Grb2	0.013	0.024	-10000	0	-0.49	1	1
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.075	0.16	-10000	0	-0.44	49	49
PRL	0.002	0.033	-10000	0	-0.49	2	2
SOCS3	-0.16	0.36	-10000	0	-1.4	32	32
SPRY2	0.005	0.069	-10000	0	-0.51	8	8
Insulin Receptor/Insulin/IRS1	-0.002	0.037	-10000	0	-0.35	5	5
CSF1/CSF1R	-0.031	0.14	-10000	0	-0.46	30	30
Ras protein signal transduction	0.02	0.036	-10000	0	-0.4	1	1
IRS1	0.013	0.029	-10000	0	-0.61	1	1
INS	-0.004	0.054	-10000	0	-0.58	4	4
LEP	-0.002	0.057	-10000	0	-0.5	6	6
STAT5B	-0.003	0.088	-10000	0	-0.3	15	15
STAT5A	-0.007	0.093	-10000	0	-0.31	17	17
GRB2	0.013	0.024	-10000	0	-0.5	1	1
PDGFB-D/PDGFRB	-0.008	0.097	-10000	0	-0.35	15	15
CSN2	-0.001	0.043	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
LAT	-0.041	0.16	-10000	0	-0.49	44	44
YBX1	0.02	0.041	-10000	0	-0.59	2	2
LCK	-0.089	0.22	-10000	0	-0.55	85	85
SHC1	0.009	0.053	-10000	0	-0.5	5	5
NOX4	-0.072	0.2	-10000	0	-0.53	73	73

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.042	0.16	-10000	0	-0.56	4	4
UGCG	-0.02	0.13	-10000	0	-0.65	16	16
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.04	0.16	-10000	0	-0.41	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.019	0.12	-10000	0	-0.62	17	17
mol:DAG	-0.004	0.045	-10000	0	-0.98	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.073	0.13	-10000	0	-0.46	26	26
FRAP1	-0.031	0.18	-10000	0	-0.5	31	31
FOXO3	-0.023	0.17	-10000	0	-0.45	34	34
AKT1	-0.035	0.18	-10000	0	-0.47	42	42
GAB2	0.013	0.029	-10000	0	-0.61	1	1
SMPD1	0.003	0.037	-10000	0	-10000	0	0
SGMS1	0.002	0.048	-10000	0	-0.67	1	1
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	0.023	0.007	-10000	0	-10000	0	0
CALM1	0.012	0.037	-10000	0	-0.55	2	2
cell proliferation	-0.015	0.11	-10000	0	-0.3	29	29
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.024	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.003	0.063	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.045	-10000	0	-0.98	1	1
natural killer cell activation	0	0.002	-10000	0	-0.012	10	10
JAK3	-0.057	0.19	-10000	0	-0.53	62	62
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.003	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	-0.045	0.25	-10000	0	-0.91	26	26
MYB	-0.087	0.34	-10000	0	-0.98	48	48
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.042	0.17	-10000	0	-0.4	57	57
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.014	0.06	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.04	0.17	-10000	0	-0.4	57	57
Rac1/GDP	0.029	0.008	-10000	0	-10000	0	0
T cell proliferation	-0.042	0.18	-10000	0	-0.49	37	37
SHC1	0.009	0.053	-10000	0	-0.5	5	5
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.001	0.02	-10000	0	-0.05	62	62
PRKCZ	-0.045	0.19	-10000	0	-0.51	38	38
NF kappa B1 p50/RelA	-0.067	0.13	-10000	0	-0.46	23	23
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.056	0.18	-10000	0	-0.44	57	57
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.064	0.18	-10000	0	-0.51	65	65
IL2RB	-0.096	0.22	-10000	0	-0.54	94	94
TERT	-0.082	0.21	-10000	0	-0.57	72	72
E2F1	-0.029	0.15	-10000	0	-0.42	50	50
SOS1	0.014	0.004	-10000	0	-10000	0	0
RPS6	0.013	0.024	-10000	0	-0.5	1	1
mol:cAMP	0	0.01	0.024	62	-10000	0	62
PTPN11	0.014	0.004	-10000	0	-10000	0	0
IL2RG	-0.041	0.17	-10000	0	-0.53	49	49
actin cytoskeleton organization	-0.042	0.18	-10000	0	-0.49	37	37
GRB2	0.013	0.024	-10000	0	-0.49	1	1
IL2	0.003	0.004	-10000	0	-10000	0	0
PIK3CA	0.016	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.016	-10000	0	-10000	0	0
LCK	-0.086	0.22	-10000	0	-0.54	85	85
BCL2	-0.018	0.18	-10000	0	-0.71	13	13

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	-0.003	0.1	-9999	-0.57	14	14
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.088	0.15	-9999	-0.37	69	69
CaM/Ca2+	-0.002	0.027	-9999	-0.4	2	2
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.05	0.15	-9999	-0.33	69	69
IQGAP1/CaM	-0.007	0.05	-9999	-0.38	8	8
DAB1	-0.087	0.22	-9999	-0.58	79	79
IQGAP1	0.007	0.062	-9999	-0.53	6	6
PLA2G7	-0.044	0.18	-9999	-0.57	46	46
CALM1	0.012	0.037	-9999	-0.55	2	2
DYNLT1	0.012	0.041	-9999	-0.61	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.02	-9999	-0.44	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0.029	-9999	-0.61	1	1
CDK5R1	-0.019	0.14	-9999	-0.6	25	25
LIS1/Poliovirus Protein 3A	0.019	0	-9999	-10000	0	0
CDK5R2	-0.11	0.24	-9999	-0.58	94	94
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.21	-9999	-0.44	127	127
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.068	0.2	-9999	-0.56	38	38
MAP1B	-0.001	0.017	-9999	-0.32	1	1
RAC1	-0.002	0.015	-9999	-10000	0	0
p35/CDK5	-0.045	0.16	-9999	-0.59	13	13
RELN	-0.14	0.25	-9999	-0.56	122	122
PAFAH/LIS1	-0.007	0.11	-9999	-0.34	46	46
LIS1/CLIP170	0.029	0.018	-9999	-0.37	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.08	0.13	-9999	-0.45	35	35
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.081	0.2	-9999	-0.68	27	27
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.082	0.21	-9999	-0.61	38	38
LIS1/IQGAP1	0.025	0.039	-9999	-0.31	6	6
RHOA	-0.002	0.015	-9999	-10000	0	0
PAFAH1B1	0.025	0	-9999	-10000	0	0
PAFAH1B3	0.014	0	-9999	-10000	0	0
PAFAH1B2	-0.003	0.1	-9999	-0.61	13	13
MAP1B/LIS1/Dynein heavy chain	0.027	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.1	0.16	-9999	-0.54	38	38
LRP8	0.013	0.029	-9999	-0.61	1	1
NDEL1/Katanin 60	-0.068	0.2	-9999	-0.56	38	38
P39/CDK5	-0.09	0.19	-9999	-0.55	36	36
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.029	0	-9999	-10000	0	0
CDK5	-0.037	0.14	-9999	-0.61	1	1
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.001	0.015	-9999	-0.32	1	1
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.1	0.19	-9999	-0.57	30	30
RELN/VLDLR	-0.087	0.14	-9999	-0.34	79	79
CDC42	-0.002	0.015	-9999	-10000	0	0

×

Noncanonical Wnt signaling 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
NFATC2	-0.066	0.2	-9999	-0.56	64	64
GNB1/GNG2	-0.018	0.13	-9999	-0.43	21	21
mol:DAG	-0.007	0.12	-9999	-0.44	12	12
PLCG1	-0.008	0.13	-9999	-0.46	12	12
YES1	-0.025	0.14	-9999	-0.45	23	23
FZD3	0.01	0.05	-9999	-0.61	3	3
FZD6	-0.013	0.12	-9999	-0.5	25	25
G protein	-0.008	0.13	-9999	-0.46	12	12
MAP3K7	-0.1	0.16	-9999	-0.42	44	44
mol:Ca2+	-0.007	0.12	-9999	-0.43	12	12
mol:IP3	-0.007	0.12	-9999	-0.44	12	12
NLK	-0.006	0.012	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.12	0.18	-9999	-0.46	47	47
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.034	0.14	-9999	-0.43	24	24
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.023	0.13	-9999	-0.42	21	21
GO:0007205	-0.007	0.12	-9999	-0.44	11	11
WNT6	-0.036	0.16	-9999	-0.54	42	42
WNT4	-0.035	0.16	-9999	-0.53	42	42
NFAT1/CK1 alpha	-0.082	0.14	-9999	-0.46	35	35
GNG2	0.009	0.057	-9999	-0.61	4	4
WNT5A	-0.018	0.13	-9999	-0.58	25	25
WNT11	-0.017	0.13	-9999	-0.56	25	25
CDC42	-0.016	0.13	-9999	-0.42	23	23

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.021	0.089	-9999	-0.38	26	26
alphaV beta3 Integrin	-0.042	0.11	-9999	-0.38	18	18
PTK2	-0.014	0.15	-9999	-0.47	23	23
IGF1R	0.013	0.024	-9999	-0.5	1	1
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.01	0.05	-9999	-0.61	3	3
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.031	0.093	-9999	-0.5	14	14
VEGFA	-0.009	0.11	-9999	-0.5	21	21
ILK	-0.031	0.093	-9999	-0.5	14	14
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	0.006	0.096	-9999	-0.46	14	14
PTK2B	-0.023	0.14	-9999	-0.41	34	34
alphaV/beta3 Integrin/JAM-A	-0.017	0.13	-9999	-0.53	8	8
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.041	0.11	-9999	-0.31	61	61
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.013	0.061	-9999	-0.33	13	13
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.009	0.089	-9999	-0.38	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.065	0.15	-9999	-0.36	84	84
PI4KA	0.006	0.066	-9999	-0.5	8	8
IGF-1R heterotetramer/IGF1/IRS1	-0.048	0.12	-9999	-0.48	16	16
PI4 Kinase	-0.006	0.045	-9999	-0.35	8	8
PIK3CA	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.095	0.17	-9999	-0.38	117	117
RPS6KB1	0.007	0.13	-9999	-0.45	16	16
TLN1	0.014	0	-9999	-10000	0	0
MAPK3	0.001	0.13	-9999	-0.45	21	21
GPR124	0.01	0.047	-9999	-0.5	4	4
MAPK1	0.001	0.13	-9999	-0.45	21	21
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.086	0.16	-9999	-0.35	114	114
cell adhesion	-0.035	0.09	-9999	-0.35	16	16
ANGPTL3	0.006	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.017	0.074	-9999	-0.31	26	26
IGF-1R heterotetramer	0.013	0.024	-9999	-0.49	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.009	0.053	-9999	-0.5	5	5
ITGB3	-0.055	0.18	-9999	-0.52	60	60
IGF1	-0.008	0.11	-9999	-0.57	18	18
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.042	0.11	-9999	-0.31	63	63
apoptosis	0.013	0.029	-9999	-0.6	1	1
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.04	0.1	-9999	-0.37	16	16
VCL	0.006	0.068	-9999	-0.54	7	7
alphaV/beta3 Integrin/Del1	-0.084	0.17	-9999	-0.37	105	105
CSF1	-0.007	0.11	-9999	-0.61	16	16
PIK3C2A	-0.033	0.1	-9999	-0.52	15	15
PI4 Kinase/Pyk2	-0.061	0.12	-9999	-0.43	30	30
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.051	0.13	-9999	-0.43	34	34
FAK1/Vinculin	-0.005	0.13	-9999	-0.42	18	18
alphaV beta3/Integrin/ppsTEM5	-0.043	0.11	-9999	-0.31	63	63
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.012	0.12	-9999	-0.56	21	21
BCAR1	0.013	0.029	-9999	-0.61	1	1
FGF2	0.011	0.047	-9999	-0.57	3	3
F11R	0.013	0.069	-9999	-0.36	15	15
alphaV/beta3 Integrin/Lactadherin	-0.043	0.11	-9999	-0.31	64	64
alphaV/beta3 Integrin/TGFBR2	-0.043	0.11	-9999	-0.4	19	19
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.013	0.063	-9999	-0.33	18	18
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.036	0.094	-9999	-0.28	61	61
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.004	0.096	-9999	-0.5	17	17
alphaV/beta3 Integrin/Pyk2	-0.023	0.14	-9999	-0.41	34	34
SDC1	-0.031	0.15	-9999	-0.51	40	40
VAV3	-0.04	0.14	-9999	-0.56	6	6
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.013	0.029	-9999	-0.61	1	1
FAK1/Paxillin	-0.002	0.13	-9999	-0.38	18	18
cell migration	0.006	0.12	-9999	-0.43	9	9
ITGAV	0.013	0.029	-9999	-0.61	1	1
PI3K	-0.045	0.1	-9999	-0.48	8	8
SPP1	-0.082	0.21	-9999	-0.55	79	79
KDR	0.006	0.066	-9999	-0.53	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.013	0.029	-9999	-0.61	1	1
COL4A3	-0.067	0.2	-9999	-0.53	69	69
angiogenesis	0.003	0.14	-9999	-0.46	21	21
Rac1/GTP	-0.064	0.11	-9999	-0.51	6	6
EDIL3	-0.061	0.2	-9999	-0.59	58	58
cell proliferation	-0.043	0.11	-9999	-0.4	19	19

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.055	-10000	0	-0.59	3	3
AES	0.007	0.023	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.003	0.039	-10000	0	-0.34	6	6
SMAD4	0.014	0	-10000	0	-10000	0	0
DKK2	-0.11	0.23	-10000	0	-0.55	103	103
TLE1	0.006	0.037	-10000	0	-0.61	1	1
MACF1	0.015	0	-10000	0	-10000	0	0
CTNNB1	0.063	0.085	-10000	0	-10000	0	0
WIF1	-0.28	0.28	-10000	0	-0.55	244	244
beta catenin/RanBP3	0.022	0.11	0.41	30	-10000	0	30
KREMEN2	-0.053	0.18	-10000	0	-0.54	56	56
DKK1	-0.12	0.24	-10000	0	-0.54	109	109
beta catenin/beta TrCP1	0.069	0.08	-10000	0	-10000	0	0
FZD1	0.009	0.053	-10000	0	-0.49	5	5
AXIN2	-0.001	0.098	-10000	0	-0.77	4	4
AXIN1	0.015	0.001	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.025	0.037	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.053	0.3	3	-10000	0	3
Axin1/APC/GSK3	0.008	0.036	0.25	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.055	0.065	-10000	0	-10000	0	0
HNF1A	0.006	0.038	0.2	1	-0.61	1	2
CTBP1	0.007	0.025	-10000	0	-10000	0	0
MYC	-0.057	0.32	-10000	0	-1.4	22	22
RANBP3	0.014	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.36	143	143
NKD1	0	0.087	-10000	0	-0.56	11	11
TCF4	0.006	0.036	-10000	0	-0.56	1	1
TCF3	0.005	0.043	-10000	0	-0.54	2	2
WNT1/LRP6/FZD1/Axin1	-0.019	0.069	-10000	0	-0.51	1	1
Ran/GTP	0.002	0.005	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.036	0.13	0.5	29	-10000	0	29
LEF1	0.002	0.057	-10000	0	-0.5	5	5
DVL1	0.061	0.048	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.088	0.079	-10000	0	-0.44	2	2
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.42	74	74
LRP6	0.014	0.024	-10000	0	-0.5	1	1
CSNK1A1	0.009	0.026	-10000	0	-10000	0	0
NLK	0.012	0.035	-10000	0	-0.52	2	2
CCND1	-0.037	0.25	-10000	0	-1.4	12	12
WNT1	-0.022	0.13	-10000	0	-0.49	31	31
GSK3A	0.015	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0.001	-10000	0	-10000	0	0
FRAT1	0.01	0.047	-10000	0	-0.57	3	3
PPP2R5D	0.042	0.046	0.29	11	-10000	0	11
APC	0.022	0.075	-10000	0	-0.47	1	1
WNT1/LRP6/FZD1	0.1	0.1	0.24	101	-10000	0	101
CREBBP	0.007	0.025	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.014	0	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.017	-10000	0	-10000	0	0
DOCK1	0.01	0.05	-10000	0	-0.61	3	3
ITGA4	-0.056	0.19	-10000	0	-0.54	58	58
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.081	0.18	-10000	0	-0.44	86	86
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.041	0.11	-10000	0	-0.33	58	58
alpha4/beta7 Integrin/Paxillin	-0.03	0.14	-10000	0	-0.37	55	55
lamellipodium assembly	0.005	0.034	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.014	0	-10000	0	-10000	0	0
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
ARF6/GTP	-0.03	0.08	-10000	0	-0.43	2	2
cell adhesion	-0.033	0.089	-10000	0	-0.31	27	27
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.004	0.11	-10000	0	-0.34	27	27
ITGB1	0.012	0.033	-10000	0	-0.5	2	2
ITGB7	-0.034	0.16	-10000	0	-0.55	40	40
ARF6/GDP	0.007	0.017	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.08	0.17	-10000	0	-0.34	114	114
p130Cas/Crk/Dock1	-0.003	0.034	-10000	0	-0.37	4	4
VCAM1	-0.14	0.26	-10000	0	-0.57	124	124
alpha4/beta1 Integrin/Paxillin/Talin	0.005	0.1	-10000	0	-0.31	27	27
alpha4/beta1 Integrin/Paxillin/GIT1	0.005	0.1	-10000	0	-0.31	27	27
BCAR1	0.013	0.029	-10000	0	-0.61	1	1
mol:GDP	0.033	0.089	0.31	27	-10000	0	27
CBL	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GIT1	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.005	0.1	-10000	0	-0.31	27	27
Rac1/GTP	0.006	0.036	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.033	0.17	-9999	-0.47	53	53
KLHL20	-0.026	0.056	-9999	-0.27	8	8
CYFIP2	0.008	0.058	-9999	-0.54	5	5
Rac1/GDP	0.01	0.11	-9999	-10000	0	0
ENAH	-0.034	0.17	-9999	-0.47	53	53
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.013	0.024	-9999	-0.5	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.035	0.068	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.017	0.039	-9999	-0.18	9	9
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.092	0.16	-9999	-0.39	67	67
RAPGEF1	-0.012	0.15	-9999	-0.39	53	53
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.073	0.16	-9999	-0.49	53	53
CRK	-0.023	0.16	-9999	-0.43	53	53
E-cadherin/gamma catenin/alpha catenin	-0.084	0.15	-9999	-0.34	115	115
alphaE/beta7 Integrin	-0.034	0.11	-9999	-0.39	40	40
IQGAP1	0.007	0.062	-9999	-0.53	6	6
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.02	-9999	-0.3	2	2
DLG1	-0.034	0.17	-9999	-0.46	54	54
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.025	0.049	-9999	-10000	0	0
MLLT4	0.013	0.029	-9999	-0.61	1	1
ARF6/GTP/NME1/Tiam1	0	0.016	-9999	-0.34	1	1
PI3K	-0.032	0.062	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.1	0.18	-9999	-0.41	115	115
TIAM1	0.013	0.029	-9999	-0.61	1	1
E-cadherin(dimer)/Ca2+	-0.063	0.12	-9999	-0.31	53	53
AKT1	-0.018	0.035	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.55	109	109
RhoA/GDP	0.009	0.11	-9999	-10000	0	0
actin cytoskeleton organization	-0.019	0.041	-9999	-0.2	8	8
CDC42/GDP	0.009	0.11	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.032	0.11	-9999	-0.28	58	58
ITGB7	-0.034	0.16	-9999	-0.55	40	40
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.067	0.12	-9999	-0.33	53	53
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.065	0.12	-9999	-0.32	53	53
mol:GDP	0	0.13	-9999	-10000	0	0
CDC42/GTP/IQGAP1	-0.004	0.037	-9999	-0.32	6	6
JUP	0.001	0.087	-9999	-0.58	10	10
p120 catenin/RhoA/GDP	-0.042	0.087	-9999	-10000	0	0
RAC1/GTP/IQGAP1	-0.004	0.037	-9999	-0.32	6	6
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.011	0.064	-9999	-0.21	26	26
NME1	0.014	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.033	0.17	-9999	-0.47	53	53
regulation of cell-cell adhesion	-0.031	0.06	-9999	-10000	0	0
WASF2	-0.008	0.02	-9999	-10000	0	0
Rap1/GTP	-0.041	0.078	-9999	-0.33	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.091	0.16	-9999	-0.53	24	24
CCND1	0.011	0.078	-9999	-0.27	26	26
VAV2	-0.017	0.16	-9999	-0.46	8	8
RAP1/GDP	-0.039	0.082	-9999	-10000	0	0
adherens junction assembly	-0.032	0.16	-9999	-0.45	53	53
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
PIP5K1C	0.014	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.052	0.17	-9999	-0.56	19	19
E-cadherin/beta catenin	-0.067	0.13	-9999	-0.39	53	53
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.035	0.17	-9999	-0.47	53	53
PIK3CA	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.042	0.091	-9999	-0.47	8	8
E-cadherin/beta catenin/alpha catenin	-0.076	0.14	-9999	-0.37	53	53
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.075	0.16	-9999	-0.5	53	53

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.017	0.069	-10000	0	-0.37	3	3
epithelial cell differentiation	-0.044	0.091	-10000	0	-0.48	7	7
ITCH	0.019	0.013	-10000	0	-10000	0	0
WWP1	0.025	0.05	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.22	-10000	0	-0.56	79	79
PRL	0	0.033	-10000	0	-0.5	2	2
neuron projection morphogenesis	-0.032	0.15	-10000	0	-0.47	7	7
PTPRZ1	0.003	0.083	-10000	0	-0.58	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.091	0.13	-10000	0	-0.45	16	16
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.078	0.17	-10000	0	-0.34	107	107
ADAM17	0.012	0.065	-10000	0	-0.6	5	5
ErbB4/ErbB4	0.022	0.064	-10000	0	-0.42	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.006	0.13	-10000	0	-0.4	38	38
NCOR1	0.013	0.029	-10000	0	-0.61	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.066	0.16	-10000	0	-0.38	23	23
GRIN2B	-0.16	0.21	-10000	0	-0.52	73	73
ErbB4/ErbB2/betacellulin	-0.033	0.14	-10000	0	-0.42	19	19
STAT1	-0.002	0.09	-10000	0	-0.5	15	15
HBEGF	0.003	0.074	-10000	0	-0.5	10	10
PRLR	-0.023	0.14	-10000	0	-0.57	30	30
E4ICDs/ETO2	0.018	0.07	-10000	0	-0.36	7	7
axon guidance	-0.015	0.079	-10000	0	-0.38	1	1
NEDD4	0.007	0.079	-10000	0	-0.54	9	9
Prolactin receptor/Prolactin receptor/Prolactin	-0.028	0.1	-10000	0	-0.41	32	32
CBFA2T3	0.005	0.074	-10000	0	-0.59	7	7
ErbB4/ErbB2/HBEGF	0.023	0.076	-10000	0	-0.37	7	7
MAPK3	-0.042	0.15	-10000	0	-0.46	11	11
STAT1 (dimer)	0.014	0.077	-10000	0	-0.4	4	4
MAPK1	-0.042	0.15	-10000	0	-0.46	11	11
JAK2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.071	0.16	-10000	0	-0.39	27	27
NRG1	-0.12	0.21	-10000	0	-0.41	150	150
NRG3	-0.035	0.17	-10000	0	-0.61	37	37
NRG2	0.012	0.041	-10000	0	-0.61	2	2
NRG4	-0.05	0.18	-10000	0	-0.53	54	54
heart development	-0.015	0.079	-10000	0	-0.38	1	1
neural crest cell migration	-0.07	0.16	-10000	0	-0.39	27	27
ERBB2	0.017	0.068	-10000	0	-0.38	13	13
WWOX/E4ICDs	0.024	0.054	-10000	0	-0.36	1	1
SHC1	0.009	0.053	-10000	0	-0.5	5	5
ErbB4/EGFR/neuregulin 4	-0.089	0.15	-10000	0	-0.48	34	34
apoptosis	0.043	0.12	0.42	38	-10000	0	38
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.022	0.063	-10000	0	-0.45	3	3
ErbB4/ErbB2/epiregulin	0.006	0.085	-10000	0	-0.4	6	6
ErbB4/ErbB4/betacellulin/betacellulin	-0.043	0.15	-10000	0	-0.37	56	56
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.031	0.08	-10000	0	-0.48	4	4
MDM2	0.027	0.058	-10000	0	-0.36	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.097	0.14	-10000	0	-0.4	13	13
STAT5A	-0.014	0.094	-10000	0	-0.43	8	8
ErbB4/EGFR/neuregulin 1 beta	-0.12	0.2	-10000	0	-0.51	54	54
DLG4	0.003	0.074	-10000	0	-0.5	10	10
GRB2/SHC	-0.004	0.039	-10000	0	-0.35	6	6
E4ICDs/TAB2/NCoR1	-0.013	0.043	-10000	0	-0.4	2	2
STAT5A (dimer)	-0.047	0.097	-10000	0	-0.54	6	6
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.073	-10000	0	-0.35	1	1
LRIG1	-0.004	0.11	-10000	0	-0.61	14	14
EREG	-0.013	0.11	-10000	0	-0.5	22	22
BTC	-0.091	0.22	-10000	0	-0.56	83	83
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.016	0.079	-10000	0	-0.38	1	1
ERBB4	0.022	0.064	-10000	0	-0.42	1	1
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.035	0.13	-10000	0	-0.6	23	23
GRB2	0.013	0.024	-10000	0	-0.5	1	1
ErbB4/ErbB2/neuregulin 4	-0.008	0.12	-10000	0	-0.39	16	16
glial cell differentiation	0.013	0.043	0.4	2	-10000	0	2
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.11	0.19	-10000	0	-0.51	41	41

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.007	0.11	-10000	0	-0.35	40	40
MAP4K4	-0.023	0.12	-10000	0	-0.46	16	16
BAG4	0.001	0.09	-10000	0	-0.61	10	10
PKC zeta/ceramide	-0.014	0.076	0.16	1	-0.28	24	25
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.035	0.16	-10000	0	-0.56	40	40
BAX	0.006	0.025	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.014	-10000	0	-10000	0	0
BAD	0.004	0.048	0.17	7	-10000	0	7
SMPD1	-0.027	0.09	-10000	0	-0.2	69	69
RB1	0.003	0.052	0.17	7	-0.41	1	8
FADD/Caspase 8	-0.014	0.12	-10000	0	-0.42	19	19
MAP2K4	0.008	0.055	-10000	0	-0.26	6	6
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.012	0.045	-10000	0	-10000	0	0
EGF	-0.047	0.18	-10000	0	-0.56	49	49
mol:ceramide	-0.006	0.052	0.17	7	-10000	0	7
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.007	0.11	-10000	0	-0.35	40	40
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.003	0.051	0.16	7	-0.41	1	8
cell proliferation	0	0.092	-10000	0	-0.43	13	13
BID	-0.011	0.092	-10000	0	-0.38	11	11
MAP3K1	0.001	0.055	0.17	5	-0.27	5	10
EIF2A	0.016	0.057	-10000	0	-0.33	4	4
TRADD	0.013	0.029	-10000	0	-0.61	1	1
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.023	0.043	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.043	-10000	0	-10000	0	0
Cathepsin D/ceramide	0.002	0.046	0.16	6	-10000	0	6
FADD	-0.023	0.12	-10000	0	-0.46	16	16
KSR1	0.004	0.048	0.17	7	-10000	0	7
MAPK8	-0.002	0.073	-10000	0	-0.28	14	14
PRKRA	0.004	0.048	0.17	7	-10000	0	7
PDGFA	-0.03	0.14	-10000	0	-0.5	40	40
TRAF2	0.014	0	-10000	0	-10000	0	0
IGF1	-0.008	0.11	-10000	0	-0.57	18	18
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.006	0.052	0.17	7	-10000	0	7
CTSD	0.013	0.024	-10000	0	-0.5	1	1
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	0.001	0.1	-10000	0	-0.47	13	13
PRKCD	-0.015	0.13	-10000	0	-0.61	22	22
PRKCZ	-0.017	0.13	-10000	0	-0.57	25	25
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.007	0.11	-10000	0	-0.35	40	40
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.027	0.15	-10000	0	-0.53	35	35
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.033	0.13	-10000	0	-0.5	16	16
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-10000	0	-0.34	154	154
mol:Sphingosine-1-phosphate	-0.007	0.11	-10000	0	-0.35	40	40
MAP2K1	0.019	0.045	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	0.008	0.039	0.19	4	-10000	0	4
TNFRSF1A	0.003	0.079	-10000	0	-0.56	9	9
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.017	0.087	-10000	0	-0.44	18	18
EIF2AK2	0.008	0.059	-10000	0	-0.32	6	6
TNF-alpha/TNFR1A/FAN	-0.1	0.16	-10000	0	-0.33	149	149
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.004	0.083	-10000	0	-0.31	11	11
MAP2K2	0.019	0.044	-10000	0	-10000	0	0
SMPD3	-0.048	0.13	-10000	0	-0.26	98	98
TNF	-0.16	0.26	-10000	0	-0.55	142	142
PKC zeta/PAR4	-0.05	0.14	-10000	0	-0.41	56	56
mol:PHOSPHOCHOLINE	0.005	0.076	0.21	39	-10000	0	39
NF kappa B1/RelA/I kappa B alpha	-0.034	0.095	-10000	0	-0.55	4	4
AIFM1	0.008	0.039	0.19	4	-10000	0	4
BCL2	0.005	0.076	-10000	0	-0.61	7	7

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.021	0.089	-9999	-0.38	26	26
PDGFRB	0.01	0.042	-9999	-0.5	3	3
SPHK1	-0.041	0.14	-9999	-0.75	16	16
mol:S1P	-0.041	0.12	-9999	-0.6	19	19
S1P1/S1P/Gi	-0.023	0.16	-9999	-0.37	56	56
GNAO1	0.004	0.071	-9999	-0.61	6	6
PDGFB-D/PDGFRB/PLCgamma1	-0.011	0.15	-9999	-0.55	11	11
PLCG1	-0.015	0.15	-9999	-0.57	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.042	-9999	-0.5	3	3
GNAI2	0.012	0.007	-9999	-10000	0	0
GNAI3	0.012	0.007	-9999	-10000	0	0
GNAI1	-0.01	0.12	-9999	-0.61	17	17
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.003	0.08	-9999	-0.32	26	26
S1P1/S1P	-0.051	0.11	-9999	-0.43	28	28
negative regulation of cAMP metabolic process	-0.021	0.15	-9999	-0.36	56	56
MAPK3	-0.039	0.21	-9999	-0.54	52	52
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.005	0.067	-9999	-0.53	7	7
PLCB2	-0.017	0.14	-9999	-0.42	31	31
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.042	0.094	-9999	-0.37	26	26
receptor internalization	-0.048	0.1	-9999	-0.38	32	32
PTGS2	-0.099	0.35	-9999	-1	52	52
Rac1/GTP	-0.042	0.094	-9999	-0.37	26	26
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	-0.01	0.11	-9999	-0.5	21	21
negative regulation of T cell proliferation	-0.021	0.15	-9999	-0.36	56	56
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.011	0.03	-9999	-0.62	1	1
MAPK1	-0.039	0.21	-9999	-0.54	52	52
S1P1/S1P/PDGFB-D/PDGFRB	-0.011	0.13	-9999	-0.42	27	27
ABCC1	0.009	0.048	-9999	-0.5	4	4

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.061	0.2	-10000	0	-0.59	58	58
HRAS	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.22	-10000	0	-0.56	79	79
AKT	0.022	0.042	-10000	0	-0.37	3	3
FOXO3	0.014	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
FOXO1	0.011	0.047	-10000	0	-0.57	3	3
AKT3	0.009	0.057	-10000	0	-0.61	4	4
FOXO4	0.013	0.029	-10000	0	-0.61	1	1
MET	-0.14	0.25	-10000	0	-0.55	129	129
PIK3CA	0.014	0	-10000	0	-10000	0	0
PIK3CB	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
PIK3CG	-0.063	0.19	-10000	0	-0.54	65	65
PIK3R3	0.012	0.033	-10000	0	-0.5	2	2
PIK3R2	0.014	0	-10000	0	-10000	0	0
NF1	0.012	0.041	-10000	0	-0.61	2	2
RAS	-0.053	0.11	0.23	1	-0.29	48	49
ERBB2	0.006	0.066	-10000	0	-0.5	8	8
proliferation/survival/translation	-0.01	0.052	0.2	9	-0.15	1	10
PI3K	-0.045	0.11	-10000	0	-0.25	70	70
PIK3R1	0.014	0	-10000	0	-10000	0	0
KRAS	0.013	0.024	-10000	0	-0.5	1	1
FOXO	0.029	0.03	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.029	-10000	0	-0.61	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.01	0.12	-10000	0	-0.41	19	19
CRKL	0.02	0.11	-10000	0	-0.41	20	20
HRAS	0	0.14	-10000	0	-0.48	13	13
mol:PIP3	0.002	0.1	-10000	0	-0.38	21	21
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.011	0.041	-10000	0	-0.5	3	3
GAB1	0.012	0.12	-10000	0	-0.44	20	20
FOXO3	0.025	0.1	-10000	0	-0.37	18	18
AKT1	0.017	0.11	-10000	0	-0.4	19	19
BAD	0.025	0.1	-10000	0	-0.37	18	18
megakaryocyte differentiation	0.003	0.13	-10000	0	-0.39	33	33
GSK3B	0.025	0.1	-10000	0	-0.37	18	18
RAF1	0.012	0.12	-10000	0	-0.39	12	12
SHC1	0.009	0.053	-10000	0	-0.5	5	5
STAT3	0.013	0.12	-10000	0	-0.43	20	20
STAT1	0.002	0.24	-10000	0	-0.93	25	25
HRAS/SPRED1	0.009	0.12	-10000	0	-0.39	12	12
cell proliferation	0.007	0.13	-10000	0	-0.44	23	23
PIK3CA	0.014	0	-10000	0	-10000	0	0
TEC	-0.007	0.11	-10000	0	-0.55	17	17
RPS6KB1	0.013	0.12	-10000	0	-0.37	29	29
HRAS/SPRED2	0.008	0.12	-10000	0	-0.39	14	14
LYN/TEC/p62DOK	-0.04	0.12	-10000	0	-0.45	27	27
MAPK3	0.024	0.091	-10000	0	-0.3	5	5
STAP1	-0.005	0.14	-10000	0	-0.43	29	29
GRAP2	-0.051	0.18	-10000	0	-0.54	54	54
JAK2	-0.052	0.18	-10000	0	-0.79	22	22
STAT1 (dimer)	0.003	0.24	-10000	0	-0.91	25	25
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.058	0.13	-10000	0	-0.46	29	29
actin filament polymerization	0.006	0.12	-10000	0	-0.43	20	20
LYN	0.003	0.078	-10000	0	-0.52	10	10
STAP1/STAT5A (dimer)	-0.005	0.18	-10000	0	-0.62	28	28
PIK3R1	0.014	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.03	0.1	-10000	0	-0.37	18	18
PI3K	0.022	0.11	-10000	0	-0.4	19	19
PTEN	0.013	0.029	-10000	0	-0.61	1	1
SCF/KIT/EPO/EPOR	-0.007	0.28	-10000	0	-1.2	20	20
MAPK8	0.006	0.13	-10000	0	-0.45	23	23
STAT3 (dimer)	0.013	0.11	-10000	0	-0.42	20	20
positive regulation of transcription	0.025	0.079	-10000	0	-0.24	5	5
mol:GDP	-0.065	0.13	0.22	1	-0.48	20	21
PIK3C2B	0.008	0.12	-10000	0	-0.41	24	24
CBL/CRKL	0.027	0.11	-10000	0	-0.39	18	18
FER	0.001	0.14	-10000	0	-0.44	33	33
SH2B3	0.012	0.12	-10000	0	-0.43	20	20
PDPK1	0.01	0.1	-10000	0	-0.36	20	20
SNAI2	-0.005	0.14	-10000	0	-0.42	30	30
positive regulation of cell proliferation	0.009	0.19	-10000	0	-0.7	25	25
KITLG	0.003	0.1	-10000	0	-0.61	12	12
cell motility	0.009	0.19	-10000	0	-0.7	25	25
PTPN6	-0.013	0.096	-10000	0	-0.55	14	14
EPOR	0.038	0.081	-10000	0	-10000	0	0
STAT5A (dimer)	0.007	0.17	-10000	0	-0.61	25	25
SOCS1	-0.032	0.15	-10000	0	-0.52	40	40
cell migration	0.04	0.17	0.38	63	-10000	0	63
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.007	0.1	-10000	0	-0.5	19	19
VAV1	-0.021	0.14	-10000	0	-0.57	28	28
GRB10	0.012	0.12	-10000	0	-0.42	21	21
PTPN11	0.013	0.005	-10000	0	-10000	0	0
SCF/KIT	0.005	0.12	0.23	7	-0.4	29	36
GO:0007205	-0.002	0.006	-10000	0	-10000	0	0
MAP2K1	0.021	0.099	-10000	0	-0.32	6	6
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.01	0.28	-10000	0	-1.3	19	19
MAP2K2	0.021	0.099	-10000	0	-0.33	5	5
SHC/Grb2/SOS1	-0.028	0.094	-10000	0	-0.4	19	19
STAT5A	0.006	0.17	-10000	0	-0.63	25	25
GRB2	0.013	0.024	-10000	0	-0.5	1	1
response to radiation	-0.004	0.13	-10000	0	-0.41	30	30
SHC/GRAP2	-0.049	0.13	-10000	0	-0.4	57	57
PTPRO	0.003	0.13	-10000	0	-0.4	33	33
SH2B2	0.005	0.12	-10000	0	-0.44	20	20
DOK1	0.013	0.029	-10000	0	-0.61	1	1
MATK	-0.041	0.17	-10000	0	-0.39	63	63
CREBBP	0.039	0.012	-10000	0	-10000	0	0
BCL2	0.023	0.18	-10000	0	-1.4	7	7

×

Ephrin B reverse 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0.086	-10000	0	-0.52	12	12
EPHB2	0.001	0.083	-10000	0	-0.53	11	11
EFNB1	-0.07	0.18	-10000	0	-0.38	107	107
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.082	0.15	-10000	0	-0.59	18	18
Ephrin B2/EPHB1-2	-0.036	0.12	-10000	0	-0.38	41	41
neuron projection morphogenesis	-0.079	0.14	-10000	0	-0.56	18	18
Ephrin B1/EPHB1-2/Tiam1	-0.06	0.18	-10000	0	-0.62	19	19
DNM1	-0.11	0.23	-10000	0	-0.53	106	106
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.01	0.088	-10000	0	-0.73	6	6
YES1	-0.01	0.12	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/NCK2	-0.059	0.18	-10000	0	-0.63	18	18
PI3K	0.012	0.087	-10000	0	-0.74	6	6
mol:GDP	-0.081	0.16	-10000	0	-0.62	19	19
ITGA2B	-0.046	0.18	-10000	0	-0.58	47	47
endothelial cell proliferation	-0.008	0.05	-10000	0	-0.31	12	12
FYN	-0.009	0.11	-10000	0	-0.96	6	6
MAP3K7	-0.008	0.089	-10000	0	-0.78	6	6
FGR	-0.009	0.11	-10000	0	-0.95	6	6
TIAM1	0.013	0.029	-10000	0	-0.61	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
RGS3	0.011	0.041	-10000	0	-0.5	3	3
cell adhesion	-0.038	0.16	-10000	0	-0.62	15	15
LYN	-0.011	0.11	-10000	0	-0.96	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.1	-10000	0	-0.92	6	6
Ephrin B1/EPHB1-2	-0.015	0.096	-10000	0	-0.84	6	6
SRC	-0.009	0.11	-10000	0	-0.95	6	6
ITGB3	-0.055	0.18	-10000	0	-0.52	60	60
EPHB1	-0.037	0.17	-10000	0	-0.61	38	38
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.006	0.051	-10000	0	-0.32	12	12
alphaIIb/beta3 Integrin	-0.089	0.18	-10000	0	-0.42	98	98
BLK	-0.029	0.12	-10000	0	-0.99	6	6
HCK	-0.014	0.12	-10000	0	-1	6	6
regulation of stress fiber formation	0.081	0.16	0.62	18	-10000	0	18
MAPK8	0.01	0.099	-10000	0	-0.73	6	6
Ephrin B1/EPHB1-2/RGS3	-0.061	0.18	-10000	0	-0.62	20	20
endothelial cell migration	-0.01	0.087	-10000	0	-0.62	7	7
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	0.002	0.088	-10000	0	-0.7	7	7
regulation of focal adhesion formation	0.081	0.16	0.62	18	-10000	0	18
chemotaxis	0.082	0.16	0.61	20	-10000	0	20
PIK3CA	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.081	0.14	-10000	0	-0.58	18	18
angiogenesis	-0.015	0.095	-10000	0	-0.83	6	6
LCK	-0.028	0.12	-10000	0	-0.98	6	6

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0	-9999	-10000	0	0
SPHK1	-0.028	0.15	-9999	-0.55	35	35
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.005	0.071	-9999	-0.3	18	18
GNAO1	0.006	0.07	-9999	-0.61	6	6
mol:Sphinganine-1-P	-0.006	0.11	-9999	-0.39	35	35
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.073	-9999	-0.52	4	4
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.02	-9999	-0.44	1	1
S1PR3	-0.036	0.16	-9999	-0.52	44	44
S1PR2	0.008	0.062	-9999	-0.58	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.015	0.055	-9999	-0.26	18	18
S1PR5	-0.14	0.26	-9999	-0.56	123	123
S1PR4	0.001	0.083	-9999	-0.5	12	12
GNAI1	-0.008	0.12	-9999	-0.61	17	17
S1P/S1P5/G12	-0.066	0.16	-9999	-0.35	76	76
S1P/S1P3/Gq	-0.012	0.12	-9999	-0.46	15	15
S1P/S1P4/Gi	0.022	0.076	-9999	-0.38	7	7
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.013	0.029	-9999	-0.61	1	1
GNA14	-0.018	0.13	-9999	-0.58	25	25
GNA15	-0.01	0.12	-9999	-0.58	19	19
GNA12	0.013	0.029	-9999	-0.61	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.005	0.076	-9999	-0.61	7	7
ABCC1	0.01	0.047	-9999	-0.5	4	4

×

Aurora A signaling

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
Aurora A/GADD45A	0.006	0.094	-9999	-0.32	27	27
BIRC5	-0.14	0.26	-9999	-0.56	127	127
NFKBIA	0.03	0.048	-9999	-0.29	1	1
CPEB1	0.001	0.09	-9999	-0.61	10	10
AKT1	0.03	0.048	-9999	-0.29	1	1
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	0.002	0.053	-9999	-0.34	5	5
NDEL1/TACC3	-0.012	0.089	-9999	-0.38	17	17
GADD45A	-0.018	0.12	-9999	-0.5	29	29
GSK3B	0.018	0.014	-9999	-10000	0	0
PAK1/Aurora A	-0.005	0.1	-9999	-0.3	33	33
MDM2	0.012	0.033	-9999	-0.5	2	2
JUB	-0.014	0.13	-9999	-0.58	22	22
TPX2	-0.039	0.15	-9999	-0.38	73	73
TP53	0.021	0.063	-9999	-0.3	10	10
DLG7	0.019	0.048	-9999	-0.3	1	1
AURKAIP1	0.013	0.024	-9999	-0.5	1	1
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.01	0.096	-9999	-0.4	17	17
G2/M transition of mitotic cell cycle	0.002	0.053	-9999	-0.34	5	5
AURKA	0.024	0.06	-9999	-0.35	1	1
AURKB	-0.086	0.14	-9999	-0.3	112	112
CDC25B	0.025	0.047	-9999	-0.28	1	1
G2/M transition checkpoint	-0.011	0.074	-9999	-0.29	21	21
mRNA polyadenylation	-0.003	0.067	-9999	-0.35	11	11
Aurora A/CPEB	-0.003	0.067	-9999	-0.35	11	11
Aurora A/TACC1/TRAP/chTOG	0.012	0.047	-9999	-10000	0	0
BRCA1	0.01	0.047	-9999	-0.5	4	4
centrosome duplication	-0.005	0.1	-9999	-0.3	33	33
regulation of centrosome cycle	-0.021	0.082	-9999	-0.37	17	17
spindle assembly	0.005	0.043	-9999	-0.3	1	1
TDRD7	0.012	0.041	-9999	-0.61	2	2
Aurora A/RasGAP/Survivin	-0.074	0.13	-9999	-0.33	55	55
CENPA	-0.059	0.13	-9999	-0.33	70	70
Aurora A/PP2A	0.026	0.046	-9999	-0.29	1	1
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.033	0.044	-9999	-0.27	1	1
negative regulation of DNA binding	0.021	0.063	-9999	-0.28	13	13
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.011	0.075	-9999	-0.3	21	21
mitotic prometaphase	0.023	0.038	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.06	-9999	-0.35	1	1
TACC1	0.014	0	-9999	-10000	0	0
TACC3	-0.022	0.13	-9999	-0.5	33	33
Aurora A/Antizyme1	0.01	0.045	-9999	-10000	0	0
Aurora A/RasGAP	0.026	0.046	-9999	-0.29	1	1
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.014	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.028	0.087	-9999	-0.29	45	45
Importin alpha/Importin beta/TPX2	-0.039	0.15	-9999	-0.38	73	73
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	-0.015	0.14	-9999	-0.37	41	41
PAK1	-0.036	0.16	-9999	-0.51	45	45
CKAP5	0.014	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.016	0.13	-10000	0	-0.54	25	25
positive regulation of NF-kappaB transcription factor activity	-0.032	0.11	-10000	0	-0.38	40	40
MAP2K4	0.03	0.066	-10000	0	-0.36	3	3
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.009	0.055	-10000	0	-0.58	4	4
TNFRSF10A	-0.022	0.14	-10000	0	-0.56	29	29
SMPD1	0.01	0.051	-10000	0	-0.23	13	13
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.003	0.093	-10000	0	-0.51	15	15
TRAIL/TRAILR2	-0.024	0.099	-10000	0	-0.4	28	28
TRAIL/TRAILR3	-0.045	0.14	-10000	0	-0.42	50	50
TRAIL/TRAILR1	-0.046	0.13	-10000	0	-0.42	51	51
TRAIL/TRAILR4	-0.033	0.11	-10000	0	-0.38	40	40
TRAIL/TRAILR1/DAP3/GTP	-0.035	0.1	-10000	0	-0.32	51	51
IKK complex	-0.01	0.031	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.003	0.094	-10000	0	-0.39	25	25
MAP3K1	0.024	0.065	-10000	0	-0.34	2	2
TRAILR4 (trimer)	-0.003	0.093	-10000	0	-0.51	15	15
TRADD	0.013	0.029	-10000	0	-0.61	1	1
TRAILR1 (trimer)	-0.022	0.14	-10000	0	-0.56	29	29
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.014	0.081	-10000	0	-0.28	3	3
CFLAR	0.013	0.024	-10000	0	-0.5	1	1
MAPK1	0.003	0.094	-10000	0	-0.39	25	25
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.032	0.091	-10000	0	-0.32	33	33
mol:ceramide	0.01	0.05	-10000	0	-0.23	13	13
FADD	0.014	0	-10000	0	-10000	0	0
MAPK8	0.031	0.082	-10000	0	-0.39	5	5
TRAF2	0.014	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.022	0.14	-10000	0	-0.54	30	30
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.038	0.11	-10000	0	-0.35	51	51
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.021	0.09	0.28	1	-0.39	14	15
JNK cascade	-0.032	0.11	-10000	0	-0.38	40	40
TRAIL (trimer)	-0.016	0.13	-10000	0	-0.54	25	25
TNFRSF10C	-0.022	0.14	-10000	0	-0.54	30	30
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.032	0.093	-10000	0	-0.32	32	32
TRAIL/TRAILR2/FADD	-0.02	0.082	-10000	0	-0.34	28	28
cell death	0.01	0.05	-10000	0	-0.23	13	13
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.061	-10000	0	-0.52	1	1
TRAILR2 (trimer)	0.009	0.055	-10000	0	-0.58	4	4
CASP8	-0.003	0.053	-10000	0	-0.81	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.017	0.068	-10000	0	-0.62	1	1

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.013	0.024	-10000	0	-0.5	1	1
NFATC1	0.031	0.094	-10000	0	-0.45	2	2
NFATC2	0.01	0.077	-10000	0	-0.28	15	15
NFATC3	0.005	0.087	-10000	0	-0.41	17	17
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.064	0.18	-10000	0	-0.53	37	37
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	-0.15	0.2	-10000	0	-0.5	77	77
BCL2/BAX	-0.007	0.054	-10000	0	-0.44	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.028	-10000	0	-0.41	2	2
CaM/Ca2+	0.01	0.028	-10000	0	-0.41	2	2
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.004	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.054	0.17	-10000	0	-0.51	37	37
Calcineurin A alpha-beta B1/BCL2	0.005	0.076	-10000	0	-0.61	7	7
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.053	0.17	0.5	37	-10000	0	37
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.012	0.033	-10000	0	-0.5	2	2
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	-0.12	0.23	-10000	0	-0.53	109	109
MAP3K8	-0.006	0.1	-10000	0	-0.51	18	18
NFAT4/CK1 alpha	-0.015	0.06	-10000	0	-0.41	3	3
MEF2D/NFAT1/Cbp/p300	0.025	0.11	-10000	0	-0.42	14	14
CABIN1	-0.065	0.18	-10000	0	-0.54	37	37
CALM1	0.012	0.038	-10000	0	-0.56	2	2
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.009	0.053	-10000	0	-0.5	5	5
CAMK4	-0.17	0.28	-10000	0	-0.58	145	145
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	-0.01	0.11	-10000	0	-0.5	22	22
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.032	0.1	-10000	0	-0.35	42	42
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.001	0.09	-10000	0	-0.61	10	10
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.001	0.081	-10000	0	-0.5	12	12
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.039	0.1	-10000	0	-0.45	5	5
PRKCH	0.014	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.003	0.041	-10000	0	-0.44	4	4
CASP3	0.013	0.024	-10000	0	-0.5	1	1
PIM1	0.008	0.058	-10000	0	-0.5	6	6
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-10000	0	-10000	0	0
apoptosis	-0.002	0.022	-10000	0	-0.34	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.004	0.078	-10000	0	-0.31	4	4
PRKCB	-0.065	0.19	-10000	0	-0.53	67	67
PRKCE	0.001	0.083	-10000	0	-0.53	11	11
JNK2/NFAT4	0.013	0.079	-10000	0	-0.37	17	17
BAD/BCL-XL	-0.001	0.016	-10000	0	-0.35	1	1
PRKCD	-0.015	0.13	-10000	0	-0.61	22	22
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.017	0.13	-10000	0	-0.57	25	25
PRKCA	0.013	0.029	-10000	0	-0.61	1	1
PRKCG	-0.19	0.27	-10000	0	-0.55	171	171
PRKCQ	-0.009	0.12	-10000	0	-0.6	18	18
FKBP38/BCL2	-0.007	0.054	-10000	0	-0.44	7	7
EP300	0.009	0.057	-10000	0	-0.61	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.029	0.099	-10000	0	-0.5	1	1
CaM/Ca2+/FKBP38	0.001	0.024	-10000	0	-0.34	2	2
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.02	0.025	-10000	0	-0.34	2	2
CaM/Ca2+/CAMK IV	-0.11	0.17	-10000	0	-0.36	146	146
NFATc/ERK1	0.038	0.089	-10000	0	-0.5	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.15	0.19	-10000	0	-0.5	77	77
NR4A1	0.016	0.15	-10000	0	-0.47	36	36
GSK3B	0.014	0.004	-10000	0	-10000	0	0
positive T cell selection	0.005	0.087	-10000	0	-0.41	17	17
NFAT1/CK1 alpha	-0.02	0.05	-10000	0	-0.36	4	4
RCH1/ KPNB1	-0.001	0.023	-10000	0	-0.35	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.004	-10000	0	-10000	0	0
AKAP5	-0.032	0.15	-10000	0	-0.5	42	42
MEF2D	0.013	0.024	-10000	0	-0.49	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.036	0.09	-10000	0	-0.42	2	2
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.005	0.076	-10000	0	-0.61	7	7

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.001	0.09	-9999	-0.61	10	10
Caspase 8 (4 units)	-0.013	0.086	-9999	-0.36	15	15
NEF	-0.006	0.034	-9999	-10000	0	0
NFKBIA	0.009	0.03	-9999	-10000	0	0
BIRC3	-0.002	0.17	-9999	-0.55	40	40
CYCS	0.022	0.088	-9999	-0.32	13	13
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.026	0.15	-9999	-0.61	28	28
MAP2K7	0.016	0.076	-9999	-0.32	2	2
protein ubiquitination	0.017	0.094	-9999	-0.41	6	6
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	-0.008	0.11	-9999	-0.56	18	18
BID	0.014	0.092	-9999	-0.33	15	15
NF-kappa-B/RelA/I kappa B alpha	-0.022	0.073	-9999	-10000	0	0
TRADD	0.013	0.029	-9999	-0.61	1	1
MAP3K5	0.009	0.057	-9999	-0.61	4	4
CFLAR	0.013	0.024	-9999	-0.5	1	1
FADD	0.014	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.022	0.073	-9999	-10000	0	0
MAPK8	0.017	0.085	-9999	-0.52	1	1
APAF1	0.014	0	-9999	-10000	0	0
TRAF1	0.002	0.084	-9999	-0.6	9	9
TRAF2	0.014	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.006	0.095	-9999	-0.3	27	27
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.001	0.12	-9999	-0.54	7	7
CHUK	0.017	0.1	-9999	-0.46	6	6
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.021	0.074	-9999	-0.32	17	17
TCRz/NEF	-0.041	0.13	-9999	-0.41	46	46
TNF	-0.16	0.26	-9999	-0.55	142	142
FASLG	-0.032	0.18	-9999	-0.53	46	46
NFKB1	0.009	0.03	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-9999	-0.34	154	154
CASP6	-0.021	0.07	-9999	-0.58	3	3
CASP7	0.03	0.16	-9999	-0.51	32	32
RELA	0.009	0.03	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.03	0.16	-9999	-0.51	32	32
TNFRSF1A	0.003	0.079	-9999	-0.56	9	9
TNFR1A/BAG4	-0.017	0.087	-9999	-0.44	18	18
CASP8	-0.004	0.094	-9999	-0.5	16	16
CASP9	0.013	0.024	-9999	-0.5	1	1
MAP3K14	0.008	0.11	-9999	-0.49	7	7
APAF-1/Caspase 9	-0.041	0.11	-9999	-0.4	34	34
BCL2	0.02	0.089	-9999	-0.49	2	2

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.021	0.069	-10000	0	-0.39	3	3
adherens junction organization	-0.03	0.12	-10000	0	-0.4	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.018	0.12	-10000	0	-0.36	15	15
FMN1	-0.062	0.16	-10000	0	-0.52	20	20
mol:IP3	0.011	0.069	-10000	0	-0.41	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.11	-10000	0	-0.28	58	58
CTNNB1	0.016	0.004	-10000	0	-10000	0	0
AKT1	0.014	0.079	-10000	0	-0.44	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.03	0.16	-10000	0	-0.42	54	54
CTNND1	0.015	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.005	0.11	-10000	0	-0.53	4	4
VASP	-0.006	0.11	-10000	0	-0.54	4	4
ZYX	-0.011	0.11	-10000	0	-0.53	5	5
JUB	-0.02	0.13	-10000	0	-0.36	22	22
EGFR(dimer)	-0.055	0.15	-10000	0	-0.34	57	57
E-cadherin/beta catenin-gamma catenin	-0.082	0.15	-10000	0	-0.33	115	115
mol:PI-3-4-5-P3	-0.03	0.064	-10000	0	-0.43	4	4
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
PI3K	-0.031	0.066	-10000	0	-0.44	4	4
FYN	0.021	0.068	-10000	0	-0.33	3	3
mol:Ca2+	0.011	0.068	-10000	0	-0.4	3	3
JUP	0.003	0.087	-10000	0	-0.58	10	10
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
mol:DAG	0.011	0.069	-10000	0	-0.41	3	3
CDH1	-0.12	0.24	-10000	0	-0.55	109	109
RhoA/GDP	-0.018	0.12	-10000	0	-0.36	15	15
establishment of polarity of embryonic epithelium	-0.006	0.11	-10000	0	-0.53	4	4
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.22	-10000	0	-0.56	79	79
CASR	0.009	0.076	-10000	0	-0.37	3	3
RhoA/GTP	-0.02	0.045	-10000	0	-0.36	3	3
AKT2	0.014	0.079	-10000	0	-0.4	4	4
actin cable formation	-0.053	0.15	-10000	0	-0.49	21	21
apoptosis	0.026	0.057	0.39	4	-10000	0	4
CTNNA1	0.015	0.002	-10000	0	-10000	0	0
mol:GDP	-0.028	0.13	-10000	0	-0.39	15	15
PIP5K1A	-0.006	0.11	-10000	0	-0.54	4	4
PLCG1	-0.024	0.053	-10000	0	-0.42	3	3
Rac1/GTP	-0.077	0.12	-10000	0	-0.4	23	23
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

S1P4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.006	0.07	-9999	-0.61	6	6
CDC42/GTP	-0.013	0.055	-9999	-0.4	4	4
PLCG1	0.029	0.067	-9999	-0.42	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.02	-9999	-0.44	1	1
cell migration	-0.013	0.054	-9999	-0.4	4	4
S1PR5	-0.14	0.26	-9999	-0.56	123	123
S1PR4	0.001	0.083	-9999	-0.5	12	12
MAPK3	0.029	0.067	-9999	-0.42	4	4
MAPK1	0.029	0.067	-9999	-0.42	4	4
S1P/S1P5/Gi	-0.038	0.14	-9999	-0.3	73	73
GNAI1	-0.008	0.12	-9999	-0.61	17	17
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.091	0.15	-9999	-0.34	123	123
RHOA	0.027	0.046	-9999	-0.31	2	2
S1P/S1P4/Gi	0.021	0.071	-9999	-0.35	8	8
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0.029	-9999	-0.61	1	1
S1P/S1P4/G12/G13	-0.008	0.045	-9999	-0.34	2	2
GNA12	0.013	0.029	-9999	-0.61	1	1
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.006	0.095	-9999	-0.33	34	34
SNTA1	-0.023	0.14	-9999	-0.58	29	29
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.005	0.098	-9999	-0.33	36	36
MAPK12	0.027	0.047	-9999	-0.34	6	6
CCND1	0.007	0.073	-9999	-0.4	12	12
p38 gamma/SNTA1	0.013	0.09	-9999	-0.31	28	28
MAP2K3	0.012	0.033	-9999	-0.5	2	2
PKN1	0.014	0	-9999	-10000	0	0
G2/M transition checkpoint	0.027	0.047	-9999	-0.34	6	6
MAP2K6	0.023	0.033	-9999	-0.33	2	2
MAPT	0.01	0.087	-9999	-0.31	24	24
MAPK13	-0.006	0.11	-9999	-0.39	34	34
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.032	-9999	-0.22	8	8

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.014	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.005	0.045	-9999	-0.84	1	1
Syndecan-3/Neurocan	-0.02	0.082	-9999	-0.91	1	1
POMC	-0.006	0.11	-9999	-0.55	17	17
EGFR	-0.083	0.22	-9999	-0.56	79	79
Syndecan-3/EGFR	-0.048	0.11	-9999	-0.91	1	1
AGRP	0.006	0.047	-9999	-0.5	4	4
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.014	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.024	0.15	-9999	-0.6	29	29
long-term memory	-0.002	0.027	-9999	-0.56	1	1
Syndecan-3/IL8	-0.086	0.13	-9999	-0.61	1	1
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
limb bud formation	-0.002	0.03	-9999	-0.63	1	1
MC4R	-0.11	0.24	-9999	-0.57	98	98
SRC	0.014	0	-9999	-10000	0	0
PTN	0.006	0.064	-9999	-0.51	7	7
FGFR/FGF/Syndecan-3	-0.002	0.031	-9999	-0.64	1	1
neuron projection morphogenesis	-0.02	0.08	-9999	-0.72	2	2
Syndecan-3/AgRP	-0.004	0.036	-9999	-0.61	1	1
Syndecan-3/AgRP/MC4R	-0.06	0.12	-9999	-0.6	3	3
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.002	0.031	-9999	-0.64	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.085	0.12	-9999	-0.6	1	1
IL8	-0.17	0.26	-9999	-0.54	151	151
Syndecan-3/Fyn/Cortactin	-0.002	0.028	-9999	-0.58	1	1
Syndecan-3/CASK	-0.002	0.029	-9999	-0.61	1	1
alpha-MSH/MC4R	-0.1	0.19	-9999	-0.43	109	109
Gamma Secretase	0	0	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.065	0.14	-10000	0	-0.35	85	85
cell-cell adhesion	0.037	0.1	0.49	14	-10000	0	14
Ephrin B/EPHB2/RasGAP	-0.022	0.084	-10000	0	-0.55	5	5
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
SHC1	0.009	0.053	-10000	0	-0.5	5	5
Ephrin B1/EPHB3	-0.003	0.03	-10000	0	-0.29	5	5
Ephrin B1/EPHB1	-0.033	0.11	-10000	0	-0.38	40	40
HRAS/GDP	-0.033	0.1	-10000	0	-0.48	12	12
Ephrin B/EPHB1/GRB7	-0.06	0.14	-10000	0	-0.61	17	17
Endophilin/SYNJ1	0.017	0.091	-10000	0	-0.5	6	6
KRAS	0.013	0.024	-10000	0	-0.5	1	1
Ephrin B/EPHB1/Src	-0.041	0.12	-10000	0	-0.58	11	11
endothelial cell migration	-0.006	0.04	-10000	0	-0.3	3	3
GRB2	0.013	0.024	-10000	0	-0.5	1	1
GRB7	-0.031	0.14	-10000	0	-0.5	38	38
PAK1	-0.007	0.14	-10000	0	-0.48	19	19
HRAS	0.014	0	-10000	0	-10000	0	0
RRAS	0.018	0.09	-10000	0	-0.52	5	5
DNM1	-0.11	0.23	-10000	0	-0.53	106	106
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.002	0.13	-10000	0	-0.56	11	11
lamellipodium assembly	-0.037	0.1	-10000	0	-0.49	14	14
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.006	0.12	-10000	0	-0.5	12	12
PIK3R1	0.014	0	-10000	0	-10000	0	0
EPHB2	0.001	0.083	-10000	0	-0.53	11	11
EPHB3	0.012	0.033	-10000	0	-0.5	2	2
EPHB1	-0.037	0.17	-10000	0	-0.61	38	38
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.032	0.096	-10000	0	-0.44	15	15
Ephrin B/EPHB2	-0.023	0.086	-10000	0	-0.39	16	16
Ephrin B/EPHB3	-0.018	0.072	-10000	0	-0.35	13	13
JNK cascade	0.006	0.12	-10000	0	-0.62	5	5
Ephrin B/EPHB1	-0.042	0.12	-10000	0	-0.38	46	46
RAP1/GDP	-0.028	0.082	-10000	0	-0.4	11	11
EFNB2	0	0.086	-10000	0	-0.52	12	12
EFNB3	-0.003	0.1	-10000	0	-0.57	14	14
EFNB1	0.011	0.041	-10000	0	-0.5	3	3
Ephrin B2/EPHB1-2	-0.041	0.12	-10000	0	-0.38	41	41
RAP1B	0.013	0.024	-10000	0	-0.5	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.038	0.11	-10000	0	-0.52	14	14
Rap1/GTP	-0.037	0.1	-10000	0	-0.49	14	14
axon guidance	-0.065	0.14	-10000	0	-0.35	85	85
MAPK3	0.022	0.11	-10000	0	-0.43	13	13
MAPK1	0.022	0.11	-10000	0	-0.43	13	13
Rac1/GDP	0.019	0.1	-10000	0	-0.43	11	11
actin cytoskeleton reorganization	-0.028	0.08	-10000	0	-0.39	12	12
CDC42/GDP	0.019	0.1	-10000	0	-0.43	11	11
PI3K	-0.006	0.04	-10000	0	-0.31	3	3
EFNA5	-0.083	0.22	-10000	0	-0.56	79	79
Ephrin B2/EPHB4	-0.008	0.05	-10000	0	-0.31	12	12
Ephrin B/EPHB2/Intersectin/N-WASP	0.023	0.072	-10000	0	-0.41	5	5
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.036	0.1	-10000	0	-0.48	14	14
PTK2	0.009	0.027	-10000	0	-10000	0	0
MAP4K4	0.006	0.12	-10000	0	-0.64	5	5
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.001	0.087	-10000	0	-0.5	14	14
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.12	-10000	0	-0.44	8	8
MAP2K1	0.014	0.11	-10000	0	-0.46	13	13
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.036	0.11	-10000	0	-0.36	40	40
cell migration	0.017	0.12	-10000	0	-0.49	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	0.017	0.093	-10000	0	-0.51	6	6
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.01	0.14	-10000	0	-0.57	13	13
HRAS/GTP	-0.04	0.11	-10000	0	-0.53	14	14
Ephrin B1/EPHB1-2	-0.036	0.11	-10000	0	-0.37	39	39
cell adhesion mediated by integrin	0.012	0.071	0.32	15	-10000	0	15
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.043	0.12	-10000	0	-0.57	14	14
RAC1-CDC42/GTP	-0.037	0.11	-10000	0	-0.5	15	15
RASA1	0.014	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.027	0.082	-10000	0	-0.41	10	10
ruffle organization	0.023	0.13	-10000	0	-0.49	14	14
NCK1	0.013	0.029	-10000	0	-0.61	1	1
receptor internalization	-0.038	0.15	-10000	0	-0.6	11	11
Ephrin B/EPHB2/KALRN	-0.029	0.092	-10000	0	-0.54	6	6
ROCK1	0.025	0.029	-10000	0	-0.26	5	5
RAS family/GDP	-0.026	0.076	-10000	0	-0.43	7	7
Rac1/GTP	-0.039	0.11	-10000	0	-0.52	14	14
Ephrin B/EPHB1/Src/Paxillin	0.003	0.11	-10000	0	-0.48	11	11

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.024	0.11	-10000	0	-0.46	1	1
epithelial cell differentiation	-0.063	0.12	-10000	0	-0.3	53	53
CYFIP2	0.008	0.058	-10000	0	-0.54	5	5
ENAH	0.009	0.1	-10000	0	-0.37	1	1
EGFR	-0.083	0.22	-10000	0	-0.56	79	79
EPHA2	-0.019	0.13	-10000	0	-0.5	30	30
MYO6	-0.026	0.12	-10000	0	-10000	0	0
CTNNB1	0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.003	0.033	-10000	0	-0.32	5	5
AQP5	-0.14	0.19	-10000	0	-0.52	68	68
CTNND1	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.026	0.12	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.032	0.13	-10000	0	-0.55	2	2
EGF	-0.047	0.18	-10000	0	-0.56	49	49
NCKAP1	0.014	0	-10000	0	-10000	0	0
AQP3	-0.078	0.13	-10000	0	-0.54	19	19
cortical microtubule organization	-0.063	0.12	-10000	0	-0.3	53	53
GO:0000145	-0.024	0.12	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.063	0.12	-10000	0	-0.31	53	53
MLLT4	0.013	0.029	-10000	0	-0.61	1	1
ARF6/GDP	-0.058	0.097	-10000	0	-0.41	9	9
ARF6	0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.019	0.069	-10000	0	-0.41	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.026	0.12	-10000	0	-0.38	2	2
PVRL2	0.012	0.037	-10000	0	-0.55	2	2
ZYX	-0.031	0.13	-10000	0	-0.53	1	1
ARF6/GTP	-0.017	0.062	-10000	0	-0.38	3	3
CDH1	-0.12	0.24	-10000	0	-0.55	109	109
EGFR/EGFR/EGF/EGF	-0.12	0.17	-10000	0	-0.53	40	40
RhoA/GDP	-0.058	0.1	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.021	0.12	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.013	0.024	-10000	0	-0.49	1	1
GIT1	0.014	0	-10000	0	-10000	0	0
IGF1R	0.013	0.024	-10000	0	-0.5	1	1
IGF1	-0.008	0.11	-10000	0	-0.57	18	18
DIAPH1	0	0.045	-10000	0	-0.64	2	2
Wnt receptor signaling pathway	0.063	0.12	0.3	53	-10000	0	53
RHOA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.058	0.098	-10000	0	-0.41	9	9
CTNNA1	0.014	0	-10000	0	-10000	0	0
VCL	-0.022	0.12	-10000	0	-10000	0	0
EFNA1	0.011	0.041	-10000	0	-0.5	3	3
LPP	-0.04	0.14	-10000	0	-0.44	5	5
Ephrin A1/EPHA2	-0.07	0.12	-10000	0	-0.47	8	8
SEC6/SEC8	-0.05	0.094	-10000	0	-0.48	3	3
MGAT3	-0.033	0.13	-10000	0	-0.56	2	2
HGF/MET	-0.16	0.18	-10000	0	-0.52	59	59
HGF	-0.078	0.2	-10000	0	-0.52	80	80
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.024	0.11	-10000	0	-0.46	1	1
actin cable formation	0.021	0.1	-10000	0	-0.32	3	3
KIAA1543	-0.062	0.17	-10000	0	-0.56	22	22
KIFC3	-0.027	0.13	-10000	0	-0.6	1	1
NCK1	0.013	0.029	-10000	0	-0.61	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ACTN1	-0.043	0.14	-10000	0	-0.47	5	5
NCK1/GIT1	-0.001	0.02	-10000	0	-0.44	1	1
mol:GDP	-0.063	0.12	-10000	0	-0.3	53	53
EXOC4	0.014	0	-10000	0	-10000	0	0
STX4	-0.026	0.12	-10000	0	-10000	0	0
PIP5K1C	-0.026	0.12	-10000	0	-10000	0	0
LIMA1	0.004	0.081	-10000	0	-0.61	8	8
ABI1	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.001	0.12	-10000	0	-0.38	5	5
adherens junction assembly	-0.042	0.17	-10000	0	-0.52	22	22
IGF-1R heterotetramer/IGF1	-0.065	0.12	-10000	0	-0.56	6	6
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.003	0.033	-10000	0	-0.41	3	3
MET	-0.14	0.25	-10000	0	-0.55	129	129
PLEKHA7	-0.035	0.14	-10000	0	-0.57	5	5
mol:GTP	-0.019	0.069	-10000	0	-0.41	3	3
establishment of epithelial cell apical/basal polarity	0.006	0.12	-10000	0	-0.46	3	3
cortical actin cytoskeleton stabilization	-0.024	0.11	-10000	0	-0.46	1	1
regulation of cell-cell adhesion	-0.021	0.12	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.024	0.11	-10000	0	-0.46	1	1

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.38	-9999	-1.1	52	52
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.066	0.18	-9999	-0.43	88	88
IFNAR2	0.013	0.007	-9999	-10000	0	0
AKT1	0.001	0.051	-9999	-0.28	2	2
ER alpha/Oestrogen	-0.012	0.093	-9999	-0.41	24	24
NFX1/SIN3/HDAC complex	0.041	0.029	-9999	-10000	0	0
EGF	-0.048	0.18	-9999	-0.56	49	49
SMG5	0.014	0	-9999	-10000	0	0
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.019	0.012	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.34	-9999	-1	51	51
SAP18	0.013	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.038	0.14	-9999	-0.5	40	40
WRN	0.01	0.05	-9999	-0.61	3	3
SP1	0.013	0.009	-9999	-10000	0	0
SP3	0.012	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.13	0.29	-9999	-0.91	51	51
Mad/Max	0.019	0.01	-9999	-10000	0	0
TERT	-0.14	0.41	-9999	-1.2	51	51
CCND1	-0.12	0.36	-9999	-1	59	59
MAX	0.013	0.006	-9999	-10000	0	0
RBBP7	0.013	0.004	-9999	-10000	0	0
RBBP4	0.013	0.004	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.004	-9999	-10000	0	0
Telomerase/911	0.033	0.039	-9999	-10000	0	0
CDKN1B	0.013	0.074	-9999	-0.55	1	1
RAD1	0.014	0	-9999	-10000	0	0
XRCC5	0.014	0	-9999	-10000	0	0
XRCC6	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.029	-9999	-0.61	1	1
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.012	0.006	-9999	-10000	0	0
JUN	0.002	0.076	-9999	-0.51	10	10
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.007	-9999	-10000	0	0
FOS	-0.095	0.22	-9999	-0.56	87	87
IFN-gamma/IRF1	-0.012	0.084	-9999	-0.35	26	26
PARP2	0.014	0	-9999	-10000	0	0
BLM	-0.053	0.18	-9999	-0.54	56	56
Telomerase	-0.038	0.1	-9999	-0.4	25	25
IRF1	-0.008	0.11	-9999	-0.49	23	23
ESR1	-0.016	0.13	-9999	-0.55	24	24
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0.022	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.046	0.031	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.046	0.031	-9999	-10000	0	0
HDAC1	0.009	0.05	-9999	-0.61	3	3
HDAC2	0.012	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.019	0.061	-9999	-0.44	8	8
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.013	0.006	-9999	-10000	0	0
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.013	0.024	-9999	-0.5	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.32	-9999	-1	51	51
NR2F2	-0.011	0.12	-9999	-0.52	24	24
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.004	0.081	-9999	-0.6	8	8
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	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	0.014	0	-9999	-10000	0	0
EGFR	-0.084	0.22	-9999	-0.56	79	79
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.096	0.21	-9999	-0.44	115	115
MYC	-0.02	0.14	-9999	-0.59	25	25
IL2	-0.003	0.014	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
TGFB1	0.004	0.081	-9999	-0.6	8	8
TRF2/BLM	-0.043	0.12	-9999	-0.36	56	56
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.1	0.35	-9999	-1	51	51
SP1/HDAC2	0.019	0.017	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.13	0.29	-9999	-0.91	51	51
Smad3/Myc	0.003	0.1	-9999	-0.37	32	32
911 complex	-0.001	0.013	-9999	-0.28	1	1
IFNG	0.003	0.047	-9999	-0.49	4	4
Telomerase/PinX1	-0.13	0.29	-9999	-0.91	51	51
Telomerase/AKT1/mTOR/p70S6K	0.01	0.074	-9999	-10000	0	0
SIN3B	0.013	0.004	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.13	0.29	-9999	-0.91	51	51
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	-0.003	0.033	-9999	-0.41	3	3
Telomerase/hnRNP C1/C2	-0.13	0.29	-9999	-0.91	51	51
E2F1	-0.017	0.12	-9999	-0.52	26	26
ZNFX1	0.013	0.004	-9999	-10000	0	0
PIF1	-0.052	0.18	-9999	-0.55	55	55
NCL	0.014	0	-9999	-10000	0	0
DKC1	0.014	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.036	0.098	0.17	2	-0.41	17	19
CaM/Ca2+	-0.002	0.027	-10000	0	-0.4	2	2
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.013	0.029	-10000	0	-0.61	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.023	0.14	0.25	53	-0.46	16	69
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.012	0.037	-10000	0	-0.55	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	-0.01	0.11	-10000	0	-0.5	22	22
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.017	-10000	0	-0.37	1	1
YWHAG	0.001	0.081	-10000	0	-0.5	12	12
ASIP	-0.096	0.23	-10000	0	-0.57	87	87
PRKCI	0.014	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	-0.002	0.027	-10000	0	-0.4	2	2
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.035	0	-10000	0	-10000	0	0
PRKCZ	-0.017	0.13	-10000	0	-0.57	25	25
TRIP10	0.006	0.07	-10000	0	-0.56	7	7
TC10/GTP/CIP4/Exocyst	-0.005	0.042	-10000	0	-0.34	7	7
AS160/14-3-3	0.002	0.089	-10000	0	-0.38	3	3
VAMP2	0.014	0	-10000	0	-10000	0	0
SLC2A4	0.022	0.15	0.28	28	-0.52	16	44
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.029	0	-10000	0	-10000	0	0
SFN	-0.12	0.23	-10000	0	-0.53	109	109
LNPEP	-0.013	0.13	-10000	0	-0.61	20	20
YWHAE	0.014	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.013	0.029	-9999	-0.61	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.012	0.033	-9999	-0.5	2	2
RAC1-CDC42/GTP/PAK family	-0.031	0.1	-9999	-0.22	92	92
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	0.05	-9999	-0.61	3	3
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
MAP3K12	0.014	0	-9999	-10000	0	0
FGR	0.011	0.041	-9999	-0.5	3	3
p38 alpha/TAB1	-0.027	0.058	-9999	-0.32	8	8
PRKG1	-0.04	0.17	-9999	-0.59	42	42
DUSP8	0	0.089	-9999	-0.54	12	12
PGK/cGMP/p38 alpha	-0.046	0.092	-9999	-0.29	42	42
apoptosis	-0.026	0.056	-9999	-0.32	7	7
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.003	0.078	-9999	-0.52	10	10
DUSP1	-0.02	0.14	-9999	-0.54	29	29
PAK1	-0.036	0.16	-9999	-0.51	45	45
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.016	-9999	-10000	0	0
TRAF6	0.013	0.029	-9999	-0.61	1	1
RAC1	0.014	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	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.005	0.1	-9999	-0.37	12	12
BLK	-0.11	0.22	-9999	-0.52	104	104
HCK	-0.01	0.11	-9999	-0.55	20	20
MAP2K3	0.012	0.033	-9999	-0.5	2	2
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	-0.007	0.11	-9999	-0.56	17	17
TRAF6/MEKK3	-0.001	0.016	-9999	-0.34	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.007	0.083	-9999	-0.33	9	9
positive regulation of innate immune response	0	0.11	-9999	-0.42	10	10
LCK	-0.089	0.22	-9999	-0.55	85	85
p38alpha-beta/MKP7	0.007	0.11	-9999	-0.44	7	7
p38alpha-beta/MKP5	-0.002	0.12	-9999	-0.41	13	13
PGK/cGMP	-0.039	0.12	-9999	-0.44	42	42
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.008	0.12	-9999	-0.43	11	11
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.11	0.24	-9999	-0.57	100	100

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.027	0.086	-10000	0	-0.32	29	29
ER alpha/Gai/GDP/Gbeta gamma	0.022	0.099	-10000	0	-0.4	17	17
AKT1	0.016	0.13	-10000	0	-0.75	12	12
PIK3CA	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.014	0.13	-10000	0	-0.76	12	12
mol:Ca2+	-0.013	0.14	-10000	0	-0.47	25	25
IGF1R	0.013	0.024	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/Striatin	-0.034	0.11	-10000	0	-0.36	44	44
SHC1	0.009	0.053	-10000	0	-0.5	5	5
apoptosis	-0.017	0.12	0.72	12	-10000	0	12
RhoA/GTP	-0.012	0.052	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.023	0.082	-10000	0	-0.4	18	18
regulation of stress fiber formation	-0.016	0.1	0.4	9	-10000	0	9
E2/ERA-ERB (dimer)	-0.029	0.1	-10000	0	-0.36	38	38
KRAS	0.013	0.024	-10000	0	-0.5	1	1
G13/GTP	-0.016	0.068	-10000	0	-0.3	24	24
pseudopodium formation	0.016	0.1	-10000	0	-0.4	9	9
E2/ER alpha (dimer)/PELP1	-0.017	0.075	-10000	0	-0.34	24	24
GRB2	0.013	0.024	-10000	0	-0.5	1	1
GNG2	0.009	0.057	-10000	0	-0.61	4	4
GNAO1	0.006	0.07	-10000	0	-0.61	6	6
HRAS	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.024	0.1	-10000	0	-0.46	13	13
E2/ER beta (dimer)	-0.015	0.077	-10000	0	-0.42	16	16
mol:GDP	-0.025	0.087	-10000	0	-0.36	25	25
mol:NADP	0.024	0.1	-10000	0	-0.46	13	13
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.014	0.15	-10000	0	-0.49	25	25
IGF-1R heterotetramer	0.013	0.024	-10000	0	-0.49	1	1
PLCB1	-0.011	0.13	-10000	0	-0.46	21	21
PLCB2	-0.011	0.14	-10000	0	-0.51	23	23
IGF1	-0.008	0.11	-10000	0	-0.57	18	18
mol:L-citrulline	0.024	0.1	-10000	0	-0.46	13	13
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.018	0.096	-10000	0	-0.76	6	6
JNK cascade	-0.015	0.077	-10000	0	-0.42	16	16
BCAR1	0.013	0.029	-10000	0	-0.61	1	1
ESR2	-0.006	0.11	-10000	0	-0.57	16	16
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.015	0.13	-10000	0	-0.55	24	24
Gq family/GDP/Gbeta gamma	0.007	0.12	-10000	0	-0.45	23	23
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.031	0.058	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.025	0.087	-10000	0	-0.42	18	18
GNAZ	0.013	0.029	-10000	0	-0.61	1	1
E2/ER alpha (dimer)	-0.021	0.09	-10000	0	-0.4	24	24
STRN	-0.014	0.13	-10000	0	-0.6	21	21
GNAL	-0.051	0.19	-10000	0	-0.6	49	49
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.005	0.077	-10000	0	-0.36	20	20
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.008	0.12	-10000	0	-0.61	17	17
HBEGF	-0.01	0.12	-10000	0	-0.49	9	9
cAMP biosynthetic process	-0.055	0.12	-10000	0	-0.31	81	81
SRC	0.03	0.095	-10000	0	-0.49	5	5
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.023	0.077	-10000	0	-0.35	14	14
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.027	0.081	-10000	0	-0.36	17	17
Gs family/GTP	-0.056	0.13	-10000	0	-0.32	81	81
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.012	-10000	0	-10000	0	0
vasodilation	0.024	0.1	-10000	0	-0.44	13	13
mol:DAG	-0.014	0.15	-10000	0	-0.49	25	25
Gs family/GDP/Gbeta gamma	-0.046	0.1	-10000	0	-0.38	20	20
MSN	0.015	0.11	-10000	0	-0.44	9	9
Gq family/GTP	-0.008	0.12	-10000	0	-0.49	19	19
mol:PI-3-4-5-P3	0.015	0.12	-10000	0	-0.73	12	12
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.024	0.1	0.44	13	-10000	0	13
GRB2/SOS1	-0.001	0.016	-10000	0	-0.35	1	1
RhoA/GDP	-0.023	0.08	-10000	0	-0.34	25	25
NOS3	0.023	0.11	-10000	0	-0.48	13	13
GNA11	0.005	0.076	-10000	0	-0.61	7	7
MAPKKK cascade	0.022	0.13	-10000	0	-0.54	16	16
E2/ER alpha (dimer)/PELP1/Src	-0.024	0.085	-10000	0	-0.42	17	17
ruffle organization	0.016	0.1	-10000	0	-0.4	9	9
ROCK2	0.03	0.083	-10000	0	-0.53	2	2
GNA14	-0.018	0.13	-10000	0	-0.58	25	25
GNA15	-0.01	0.12	-10000	0	-0.58	19	19
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.041	0.15	-10000	0	-0.46	17	17
MMP2	0.024	0.11	-10000	0	-0.5	7	7

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.022	0.096	-10000	0	-0.43	24	24
ATM	0.014	0	-10000	0	-10000	0	0
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.016	0.057	-10000	0	-0.35	5	5
protein ubiquitination	-0.025	0.094	-10000	0	-0.35	30	30
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.014	0.058	-10000	0	-0.39	7	7
FANCF	0.014	0	-10000	0	-10000	0	0
BRCA1	0.01	0.047	-10000	0	-0.5	4	4
CCNE1	0.012	0.033	-10000	0	-0.5	2	2
CDK2/Cyclin E1	-0.012	0.07	-10000	0	-0.4	14	14
FANCG	0.013	0.024	-10000	0	-0.5	1	1
BRCA1/BACH1/BARD1	-0.025	0.1	-10000	0	-0.43	27	27
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.011	0.044	-10000	0	-0.53	3	3
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	-0.029	0.15	-10000	0	-0.52	37	37
DNA repair	0.017	0.15	-10000	0	-0.53	15	15
BRCA1/BARD1/ubiquitin	-0.025	0.1	-10000	0	-0.43	27	27
BARD1/DNA-PK	-0.017	0.071	-10000	0	-0.33	22	22
FANCL	0.014	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.022	0.096	0.43	24	-10000	0	24
BRCA1/BARD1/CTIP/M/R/N Complex	0.029	0.067	-10000	0	-0.37	2	2
BRCA1/BACH1/BARD1/TopBP1	-0.021	0.086	-10000	0	-0.36	27	27
BRCA1/BARD1/P53	-0.029	0.097	-10000	0	-0.35	34	34
BARD1/CSTF1/BRCA1	-0.021	0.086	-10000	0	-0.36	27	27
BRCA1/BACH1	0.01	0.047	-10000	0	-0.49	4	4
BARD1	-0.017	0.14	-10000	0	-0.6	24	24
PCNA	0.012	0.033	-10000	0	-0.5	2	2
BRCA1/BARD1/UbcH5C	-0.021	0.086	-10000	0	-0.36	27	27
BRCA1/BARD1/UbcH7	-0.021	0.086	-10000	0	-0.36	27	27
BRCA1/BARD1/RAD51/PCNA	-0.053	0.13	-10000	0	-0.39	38	38
BARD1/DNA-PK/P53	-0.024	0.086	-10000	0	-0.62	2	2
BRCA1/BARD1/Ubiquitin	-0.025	0.1	-10000	0	-0.43	27	27
BRCA1/BARD1/CTIP	0.014	0.093	-10000	0	-0.36	23	23
FA complex	0.028	0.059	-10000	0	-10000	0	0
BARD1/EWS	-0.022	0.096	-10000	0	-0.43	24	24
RBBP8	0.023	0.03	-10000	0	-0.35	3	3
TP53	-0.004	0.1	-10000	0	-0.6	14	14
TOPBP1	0.014	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.028	0.097	0.35	34	-10000	0	34
BRCA1/BARD1	-0.026	0.095	-10000	0	-0.35	30	30
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.023	0.098	-10000	0	-0.44	24	24
CDK2	-0.001	0.092	-10000	0	-0.54	13	13
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.052	0.18	-10000	0	-0.52	57	57
RAD50	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.025	0.1	-10000	0	-0.43	27	27
EWSR1	0.014	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.017	0.12	-10000	0	-0.47	16	16
BAG4	0.001	0.09	-10000	0	-0.61	10	10
BAD	0.008	0.045	-10000	0	-0.2	1	1
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.035	0.16	-10000	0	-0.56	40	40
BAX	0.008	0.045	-10000	0	-0.2	1	1
EnzymeConsortium:3.1.4.12	-0.003	0.033	-10000	0	-0.1	16	16
IKBKB	-0.007	0.12	-10000	0	-0.43	16	16
MAP2K2	0.018	0.049	-10000	0	-10000	0	0
MAP2K1	0.018	0.051	-10000	0	-0.31	1	1
SMPD1	0.003	0.033	-10000	0	-0.14	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.12	-10000	0	-0.44	17	17
MAP2K4	0.011	0.054	-10000	0	-0.29	3	3
protein ubiquitination	-0.006	0.12	-10000	0	-0.44	16	16
EnzymeConsortium:2.7.1.37	0.019	0.057	-10000	0	-0.3	1	1
response to UV	0	0.001	-10000	0	-0.002	2	2
RAF1	0.013	0.049	-10000	0	-10000	0	0
CRADD	0.015	0	-10000	0	-10000	0	0
mol:ceramide	0	0.047	-10000	0	-0.16	11	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.015	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.053	-10000	0	-0.24	6	6
TRADD	0.013	0.029	-10000	0	-0.61	1	1
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.021	0.05	-10000	0	-10000	0	0
MAPK1	0.021	0.05	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	-0.016	0.12	-10000	0	-0.47	16	16
KSR1	0.007	0.048	-10000	0	-0.21	1	1
MAPK8	0.013	0.067	-10000	0	-0.29	7	7
TRAF2	0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.007	0.12	-10000	0	-0.43	16	16
TNF R/SODD	-0.015	0.087	-10000	0	-0.44	18	18
TNF	-0.16	0.26	-10000	0	-0.55	142	142
CYCS	0.012	0.044	0.15	3	-0.17	2	5
IKBKG	-0.007	0.12	-10000	0	-0.43	16	16
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.026	0.13	-10000	0	-0.5	16	16
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.012	0.044	0.15	3	-0.19	1	4
TNF/TNF R/SODD	-0.11	0.17	-10000	0	-0.34	154	154
TNFRSF1A	0.003	0.079	-10000	0	-0.56	9	9
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.053	-10000	0	-0.72	1	1
NSMAF	-0.016	0.12	-10000	0	-0.46	16	16
response to hydrogen peroxide	0	0.001	-10000	0	-0.002	2	2
BCL2	0.005	0.076	-10000	0	-0.61	7	7

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.11	0.24	-9999	-0.57	96	96
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0	-9999	-10000	0	0
TCEB1	0.014	0	-9999	-10000	0	0
HIF1A/p53	0.023	0.056	-9999	-0.28	13	13
HIF1A	0.024	0.021	-9999	-0.2	1	1
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.11	0.24	-9999	-0.58	96	96
ARNT/IPAS	-0.085	0.17	-9999	-0.4	97	97
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.032	0.025	-9999	-0.31	1	1
CUL2	0.014	0	-9999	-10000	0	0
OS9	0.004	0.07	-9999	-0.5	9	9
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.032	0.02	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.054	-9999	-0.33	8	8
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.01	-9999	-10000	0	0
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.032	0.02	-9999	-10000	0	0
EGLN3	0.004	0.081	-9999	-0.61	8	8
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	-0.004	0.1	-9999	-0.6	14	14
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.042	0.005	-9999	-10000	0	0
ARNT	0.013	0.024	-9999	-0.5	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.029	0.12	-9999	-0.29	76	76

×

Regulation of Androgen receptor activity

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
HDAC1	0.022	0.037	-9999	-0.44	3	3
SMARCC1	0.01	0.013	-9999	-10000	0	0
REL	-0.022	0.14	-9999	-0.58	29	29
HDAC7	0.023	0.1	-9999	-0.45	1	1
JUN	0.002	0.076	-9999	-0.51	10	10
EP300	0.009	0.057	-9999	-0.61	4	4
KAT2B	0.013	0.024	-9999	-0.5	1	1
KAT5	0.014	0	-9999	-10000	0	0
MAPK14	0.023	0.025	-9999	-0.44	1	1
FOXO1	0.01	0.047	-9999	-0.57	3	3
T-DHT/AR	0.019	0.11	-9999	-0.4	7	7
MAP2K6	0.012	0.029	-9999	-0.6	1	1
BRM/BAF57	0.004	0.023	-9999	-0.44	1	1
MAP2K4	0.012	0.034	-9999	-0.5	2	2
SMARCA2	0.012	0.029	-9999	-0.61	1	1
PDE9A	-0.025	0.11	-9999	-0.77	5	5
NCOA2	-0.025	0.15	-9999	-0.61	29	29
CEBPA	-0.016	0.13	-9999	-0.57	24	24
EHMT2	0.013	0.004	-9999	-10000	0	0
cell proliferation	0.033	0.13	-9999	-0.46	8	8
NR0B1	-0.097	0.23	-9999	-0.56	89	89
EGR1	-0.11	0.23	-9999	-0.54	99	99
RXRs/9cRA	-0.035	0.11	-9999	-0.33	57	57
AR/RACK1/Src	-0.008	0.075	-9999	-0.38	8	8
AR/GR	-0.012	0.11	-9999	-0.39	15	15
GNB2L1	0.014	0.001	-9999	-10000	0	0
PKN1	0.014	0	-9999	-10000	0	0
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.012	0.073	-9999	-0.43	12	12
T-DHT/AR/TIF2/CARM1	0.002	0.13	-9999	-0.66	10	10
SRC	0.031	0.061	-9999	-0.31	1	1
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.042	0.14	-9999	-0.47	20	20
APPBP2	0.014	0.005	-9999	-10000	0	0
TRIM24	0.012	0.024	-9999	-0.5	1	1
T-DHT/AR/TIP60	0.015	0.082	-9999	-0.42	7	7
TMPRSS2	-0.14	0.32	-9999	-1.1	41	41
RXRG	-0.061	0.2	-9999	-0.6	57	57
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.001	-9999	-10000	0	0
RXRB	0.014	0.001	-9999	-10000	0	0
CARM1	0.014	0.001	-9999	-10000	0	0
NR2C2	0.005	0.076	-9999	-0.61	7	7
KLK2	-0.002	0.14	-9999	-0.47	18	18
AR	-0.02	0.13	-9999	-0.41	18	18
SENP1	0.014	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.013	0.034	-9999	-0.5	2	2
SRY	-0.019	0.11	-9999	-0.49	22	22
GATA2	-0.006	0.11	-9999	-0.58	16	16
MYST2	0.014	0.001	-9999	-10000	0	0
HOXB13	-0.052	0.16	-9999	-0.5	53	53
T-DHT/AR/RACK1/Src	0.022	0.082	-9999	-0.39	7	7
positive regulation of transcription	-0.006	0.11	-9999	-0.58	16	16
DNAJA1	0.014	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.025	-9999	-0.25	3	3
NCOA1	0.018	0.005	-9999	-10000	0	0
SPDEF	-0.045	0.17	-9999	-0.55	48	48
T-DHT/AR/TIF2	0.018	0.12	-9999	-0.62	10	10
T-DHT/AR/Hsp90	0.015	0.082	-9999	-0.42	7	7
GSK3B	0.014	0.004	-9999	-10000	0	0
NR2C1	0.015	0.001	-9999	-10000	0	0
mol:T-DHT	0.025	0.065	-9999	-0.32	12	12
SIRT1	0.014	0	-9999	-10000	0	0
ZMIZ2	0.015	0.005	-9999	-10000	0	0
POU2F1	0.024	0.033	-9999	-0.6	1	1
T-DHT/AR/DAX-1	-0.045	0.15	-9999	-0.41	33	33
CREBBP	0.014	0	-9999	-10000	0	0
SMARCE1	0.014	0.003	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.1	-9999	-0.66	4	4
CRKL	0.035	0.076	-9999	-0.47	4	4
mol:DAG	0.039	0.082	-9999	-0.48	5	5
HRAS	0.057	0.078	-9999	-0.62	2	2
MAPK8	0.014	0.099	-9999	-0.41	14	14
RAP1A	0.035	0.076	-9999	-0.47	4	4
GAB1	0.034	0.083	-9999	-0.54	4	4
MAPK14	0.022	0.078	-9999	-0.41	5	5
EPO	-0.006	0.1	-9999	-0.5	19	19
PLCG1	0.039	0.084	-9999	-0.49	5	5
EPOR/TRPC2/IP3 Receptors	0.014	0.035	-9999	-0.5	2	2
RAPGEF1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.069	0.17	-9999	-0.34	128	128
GAB1/SHC/GRB2/SOS1	-0.016	0.066	-9999	-0.52	4	4
EPO/EPOR (dimer)	0.009	0.081	-9999	-0.36	20	20
IRS2	0.035	0.082	-9999	-0.54	4	4
STAT1	0.042	0.1	-9999	-0.5	8	8
STAT5B	0.044	0.087	-9999	-0.56	4	4
cell proliferation	0.023	0.093	-9999	-0.46	7	7
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.017	0.071	-9999	-0.44	8	8
TEC	0.024	0.099	-9999	-0.44	10	10
SOCS3	-0.12	0.24	-9999	-0.53	116	116
STAT1 (dimer)	0.042	0.1	-9999	-0.49	8	8
JAK2	0.015	0.007	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.041	0.083	-9999	-0.5	4	4
EPO/EPOR	0.009	0.081	-9999	-0.36	20	20
LYN	0.005	0.078	-9999	-0.52	10	10
TEC/VAV2	0.033	0.097	-9999	-0.42	10	10
elevation of cytosolic calcium ion concentration	0.014	0.035	-9999	-0.5	2	2
SHC1	0.009	0.053	-9999	-0.5	5	5
EPO/EPOR (dimer)/LYN	0.02	0.088	-9999	-0.36	14	14
mol:IP3	0.039	0.082	-9999	-0.48	5	5
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.007	0.078	-9999	-0.45	9	9
SH2B3	0.013	0.034	-9999	-0.49	2	2
NFKB1	0.022	0.078	-9999	-0.41	5	5
EPO/EPOR (dimer)/JAK2/SOCS3	-0.043	0.078	-9999	-0.27	14	14
PTPN6	0.027	0.079	-9999	-0.5	4	4
TEC/VAV2/GRB2	0.039	0.095	-9999	-0.42	9	9
EPOR	0.014	0.035	-9999	-0.5	2	2
INPP5D	0.008	0.058	-9999	-0.54	5	5
mol:GDP	-0.016	0.067	-9999	-0.49	5	5
SOS1	0.014	0	-9999	-10000	0	0
PLCG2	0.001	0.086	-9999	-0.55	11	11
CRKL/CBL/C3G	0.049	0.072	-9999	-0.43	4	4
VAV2	0.035	0.076	-9999	-0.47	4	4
CBL	0.035	0.076	-9999	-0.47	4	4
SHC/Grb2/SOS1	-0.016	0.064	-9999	-0.46	5	5
STAT5A	0.035	0.12	-9999	-0.6	9	9
GRB2	0.013	0.024	-9999	-0.5	1	1
STAT5 (dimer)	0.055	0.12	-9999	-0.6	9	9
LYN/PLCgamma2	0.005	0.096	-9999	-0.48	16	16
PTPN11	0.014	0	-9999	-10000	0	0
BTK	0.023	0.11	-9999	-0.5	13	13
BCL2	0.052	0.15	-9999	-0.93	8	8

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.041	-9999	-0.5	3	3
alphaV beta3 Integrin	-0.049	0.13	-9999	-0.37	61	61
PTK2	-0.033	0.11	-9999	-0.54	17	17
positive regulation of JNK cascade	-0.009	0.048	-9999	-0.33	9	9
CDC42/GDP	0.046	0.079	-9999	-0.45	9	9
Rac1/GDP	0.048	0.078	-9999	-0.45	9	9
RAP1B	0.013	0.024	-9999	-0.5	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.011	0.06	-9999	-0.41	9	9
nectin-3/I-afadin	-0.009	0.061	-9999	-0.44	9	9
RAPGEF1	0.039	0.088	-9999	-0.52	9	9
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.032	0.1	-9999	-0.6	9	9
PDGFB-D/PDGFRB	0.011	0.041	-9999	-0.49	3	3
TLN1	0.032	0.037	-9999	-0.35	2	2
Rap1/GTP	-0.01	0.052	-9999	-0.35	9	9
IQGAP1	0.007	0.062	-9999	-0.53	6	6
Rap1/GTP/I-afadin	-0.001	0.02	-9999	-0.3	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.009	0.061	-9999	-0.44	9	9
PVR	0.014	0	-9999	-10000	0	0
Necl-5(dimer)	0.014	0	-9999	-10000	0	0
mol:GDP	0.043	0.096	-9999	-0.57	9	9
MLLT4	0.013	0.029	-9999	-0.61	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.007	0.049	-9999	-0.55	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.016	0.083	-9999	-0.44	17	17
positive regulation of lamellipodium assembly	-0.01	0.051	-9999	-0.35	9	9
PVRL1	-0.007	0.11	-9999	-0.61	16	16
PVRL3	0.004	0.081	-9999	-0.61	8	8
PVRL2	0.012	0.037	-9999	-0.55	2	2
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.55	109	109
CLDN1	-0.015	0.12	-9999	-0.54	25	25
JAM-A/CLDN1	-0.028	0.092	-9999	-0.36	22	22
SRC	-0.021	0.1	-9999	-0.69	9	9
ITGB3	-0.055	0.18	-9999	-0.52	60	60
nectin-1(dimer)/I-afadin/I-afadin	-0.016	0.083	-9999	-0.44	17	17
FARP2	0.037	0.093	-9999	-0.56	9	9
RAC1	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.007	0.051	-9999	-0.37	9	9
nectin-1/I-afadin	-0.016	0.083	-9999	-0.44	17	17
nectin-2/I-afadin	-0.003	0.033	-9999	-0.41	3	3
RAC1/GTP/IQGAP1/filamentous actin	-0.004	0.037	-9999	-0.32	6	6
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.02	0.089	-9999	-0.4	23	23
CDC42/GTP/IQGAP1/filamentous actin	-0.004	0.037	-9999	-0.32	6	6
F11R	0.001	0.083	-9999	-0.5	12	12
positive regulation of filopodium formation	-0.009	0.048	-9999	-0.33	9	9
alphaV/beta3 Integrin/Talin	0.01	0.1	-9999	-0.46	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.003	0.033	-9999	-0.41	3	3
nectin-2(dimer)/I-afadin/I-afadin	-0.003	0.033	-9999	-0.41	3	3
PIP5K1C	0.024	0.039	-9999	-0.38	2	2
VAV2	0.036	0.094	-9999	-0.57	9	9
RAP1/GDP	-0.011	0.06	-9999	-0.42	9	9
ITGAV	0.013	0.029	-9999	-0.61	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.009	0.055	-9999	-0.37	10	10
nectin-3(dimer)/I-afadin/I-afadin	-0.009	0.061	-9999	-0.44	9	9
Rac1/GTP	-0.011	0.062	-9999	-0.43	9	9
PTPRM	0.016	0.043	-9999	-0.26	10	10
E-cadherin/beta catenin/alpha catenin	-0.069	0.13	-9999	-0.6	8	8
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.013	0.047	-9999	-10000	0	0
DAPP1	-0.037	0.15	-9999	-0.42	36	36
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.088	0.22	-9999	-0.53	61	61
mol:DAG	-0.027	0.11	-9999	-0.29	24	24
HRAS	0.014	0.003	-9999	-10000	0	0
RAP1A	0.014	0.003	-9999	-10000	0	0
ARF5/GDP	0.029	0.059	-9999	-0.29	6	6
PLCG2	0.001	0.086	-9999	-0.55	11	11
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.015	0.054	-9999	-10000	0	0
ARF1/GTP	-0.012	0.044	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.01	0.05	-9999	-0.61	3	3
RAP1A/GTP	-0.015	0.053	-9999	-10000	0	0
ADAP1	-0.03	0.09	-9999	-0.48	9	9
ARAP3	-0.015	0.054	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.001	0.09	-9999	-0.61	10	10
ARHGEF6	0.008	0.064	-9999	-0.61	5	5
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.014	0.003	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.011	0.041	-9999	-0.5	3	3
mol:Ca2+	-0.004	0.058	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.013	0.029	-9999	-0.61	1	1
ZAP70	-0.053	0.18	-9999	-0.54	56	56
mol:IP3	-0.01	0.077	-9999	-0.22	9	9
LYN	0.003	0.078	-9999	-0.52	10	10
ARF1/GDP	0.029	0.059	-9999	-0.29	6	6
RhoA/GDP	-0.015	0.045	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.017	-9999	-0.37	1	1
BLNK	-0.055	0.19	-9999	-0.59	53	53
actin cytoskeleton reorganization	0.043	0.078	-9999	-0.38	5	5
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.029	0.036	-9999	-0.32	5	5
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0.001	0.029	-9999	-0.58	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.013	0.047	-9999	-10000	0	0
RhoA/GTP	-0.014	0.049	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.082	0.21	-9999	-0.53	53	53
BLK	-0.11	0.22	-9999	-0.52	104	104
PDPK1	0.013	0.029	-9999	-0.61	1	1
CYTH1	-0.014	0.049	-9999	-10000	0	0
HCK	-0.01	0.11	-9999	-0.55	20	20
CYTH3	-0.014	0.049	-9999	-10000	0	0
CYTH2	-0.014	0.049	-9999	-10000	0	0
KRAS	0.013	0.024	-9999	-0.49	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.027	0.084	-9999	-0.46	11	11
SGK1	-0.02	0.079	-9999	-0.5	11	11
INPP5D	0.008	0.058	-9999	-0.54	5	5
mol:GDP	0.022	0.061	-9999	-0.31	6	6
SOS1	0.014	0	-9999	-10000	0	0
SYK	-0.012	0.12	-9999	-0.57	21	21
ARF6/GDP	-0.015	0.045	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.054	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.015	0.054	-9999	-10000	0	0
VAV1	-0.021	0.14	-9999	-0.57	28	28
mol:PI-3-4-P2	0.021	0.043	-9999	-0.38	5	5
RAS family/GTP/PI3K Class I	0.017	0.063	-9999	-10000	0	0
PLEKHA1	0.025	0.051	-9999	-0.3	11	11
Rac1/GDP	0.029	0.059	-9999	-0.29	6	6
LAT	-0.022	0.14	-9999	-0.6	27	27
Rac1/GTP	0.023	0.09	-9999	-0.46	10	10
ITK	-0.066	0.12	-9999	-0.43	20	20
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.044	0.14	-9999	-0.39	32	32
LCK	-0.089	0.22	-9999	-0.55	85	85
BTK	-0.024	0.07	-9999	-0.43	1	1

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.012	0.034	-10000	0	-0.31	5	5
TRAF2/ASK1	-0.003	0.035	-10000	0	-0.38	4	4
ATM	0.014	0	-10000	0	-10000	0	0
MAP2K3	0.021	0.052	-10000	0	-0.31	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.021	0.068	-10000	0	-0.45	4	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.032	0.16	-10000	0	-0.55	38	38
TXN	0.009	0.01	-10000	0	-0.21	1	1
CALM1	0.012	0.037	-10000	0	-0.55	2	2
GADD45A	-0.018	0.12	-10000	0	-0.5	29	29
GADD45B	-0.027	0.14	-10000	0	-0.53	35	35
MAP3K1	0.009	0.053	-10000	0	-0.5	5	5
MAP3K6	0.007	0.062	-10000	0	-0.5	7	7
MAP3K7	0.014	0	-10000	0	-10000	0	0
MAP3K4	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.009	0.058	-10000	0	-0.38	11	11
TAK1/TAB family	0.001	0.019	0.19	4	-0.18	1	5
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.007	0.024	-10000	0	-10000	0	0
TRAF6	0.009	0.018	-10000	0	-0.37	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.075	0.21	-10000	0	-0.55	73	73
CCM2	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.054	0.13	-10000	0	-0.34	73	73
MAPK11	0.009	0.057	-10000	0	-0.61	4	4
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.051	0.12	-10000	0	-0.32	74	74
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	-0.014	0.11	-10000	0	-0.36	40	40
TAOK2	0.019	0	-10000	0	-10000	0	0
TAOK3	0.019	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.014	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.057	-10000	0	-0.61	4	4
MAP3K10	0.006	0.066	-10000	0	-0.5	8	8
MAP3K3	0.014	0	-10000	0	-10000	0	0
TRX/ASK1	0.014	0.04	-10000	0	-0.41	4	4
GADD45/MTK1/MTK1	-0.057	0.13	-10000	0	-0.38	43	43

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.087	0.032	-9999	-10000	0	0
ERC1	0.013	0.024	-9999	-0.5	1	1
RIP2/NOD2	-0.022	0.091	-9999	-0.38	27	27
NFKBIA	0.051	0	-9999	-10000	0	0
BIRC2	0.014	0	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.008	0.034	-9999	-10000	0	0
IKK complex/A20	-0.072	0.1	-9999	-0.45	6	6
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.047	0.043	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.006	0.026	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.001	0.017	-9999	-0.37	1	1
NOD2	-0.018	0.13	-9999	-0.54	27	27
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.018	0	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0	-9999	-10000	0	0
TNF/TNFR1A	-0.13	0.19	-9999	-0.4	149	149
TRAF6	0.013	0.029	-9999	-0.61	1	1
PRKCA	0.013	0.029	-9999	-0.61	1	1
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.16	0.26	-9999	-0.55	142	142
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.051	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.018	0	-9999	-10000	0	0
TNFRSF1A	0.003	0.079	-9999	-0.56	9	9
IKK complex	0.053	0.042	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.028	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.035	0.029	-9999	-0.3	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.045	0.095	-9999	-0.43	11	11
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.003	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.08	-9999	-0.32	21	21
CaM/Ca2+	-0.003	0.025	-9999	-0.29	1	1
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.034	0.064	-9999	-0.33	6	6
AKT1	0.054	0.024	-9999	-10000	0	0
MAP2K1	0.048	0.041	-9999	-10000	0	0
MAP3K11	0.042	0.027	-9999	-0.28	1	1
IFNGR1	0.016	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.2	-9999	-0.47	93	93
Rap1/GTP	-0.001	0.014	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0	0.023	-9999	-10000	0	0
CEBPB	0.062	0.11	-9999	-0.5	10	10
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.005	0.18	-9999	-1.1	9	9
STAT1	0.035	0.064	-9999	-0.33	6	6
CALM1	0.012	0.037	-9999	-0.55	2	2
IFN-gamma (dimer)	0.002	0.046	-9999	-0.49	4	4
PIK3CA	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.039	0.068	-9999	-0.39	1	1
CEBPB/PTGES2/Cbp/p300	-0.015	0.059	-9999	-0.36	7	7
mol:Ca2+	-0.002	0.021	-9999	-0.29	1	1
MAPK3	0.056	0.049	-9999	-10000	0	0
STAT1 (dimer)	-0.073	0.11	-9999	-0.47	21	21
MAPK1	0.056	0.049	-9999	-10000	0	0
JAK2	0.016	0.002	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.016	0.002	-9999	-10000	0	0
CAMK2D	0.013	0.029	-9999	-0.61	1	1
DAPK1	0.052	0.13	-9999	-0.63	15	15
SMAD7	0.007	0.067	-9999	-0.19	4	4
CBL/CRKL/C3G	0.001	0.019	-9999	-10000	0	0
PI3K	-0.002	0.018	-9999	-10000	0	0
IFNG	0.002	0.046	-9999	-0.49	4	4
apoptosis	0.032	0.094	-9999	-0.45	15	15
CAMK2G	0.013	0.029	-9999	-0.61	1	1
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.23	0.28	-9999	-0.55	205	205
CAMK2B	-0.075	0.21	-9999	-0.55	73	73
FRAP1	0.052	0.023	-9999	-10000	0	0
PRKCD	0.041	0.071	-9999	-10000	0	0
RAP1B	0.013	0.024	-9999	-0.5	1	1
negative regulation of cell growth	-0.055	0.08	-9999	-0.32	21	21
PTPN2	0.014	0	-9999	-10000	0	0
EP300	0.009	0.058	-9999	-0.61	4	4
IRF1	0.034	0.14	-9999	-0.53	19	19
STAT1 (dimer)/PIASy	0.041	0.064	-9999	-0.39	1	1
SOCS1	-0.049	0.2	-9999	-1	13	13
mol:GDP	-0.001	0.016	-9999	-10000	0	0
CASP1	-0.003	0.091	-9999	-0.29	26	26
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.051	0.049	-9999	-0.24	5	5
mol:PI-3-4-5-P3	-0.002	0.017	-9999	-10000	0	0
RAP1/GDP	-0.001	0.015	-9999	-10000	0	0
CBL	0.042	0.026	-9999	-10000	0	0
MAP3K1	0.04	0.039	-9999	-10000	0	0
PIAS1	0.009	0.057	-9999	-0.61	4	4
PIAS4	0.014	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.08	-9999	-0.32	21	21
PTPN11	0.035	0.027	-9999	-0.29	1	1
CREBBP	0.015	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.01	0.057	-9999	-0.35	13	13
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.006	0.091	-9999	-0.37	21	21
NF kappa B1 p50/RelA/I kappa B alpha	0.013	0.083	-9999	-0.5	2	2
NFKBIA	-0.012	0.094	-9999	-0.23	55	55
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.029	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	-0.023	0.14	-9999	-0.58	29	29
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.052	-9999	-0.28	13	13
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.029	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.004	0.09	-9999	-0.44	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.018	0.081	-9999	-0.49	2	2
SRC	0.014	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.09	-9999	-0.45	2	2
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	-0.012	0.12	-9999	-0.57	21	21
I kappa B alpha/PIK3R1	-0.003	0.088	-9999	-0.55	2	2
cell death	0.017	0.078	-9999	-0.47	2	2
NF kappa B1 p105/c-Rel	0.006	0.091	-9999	-0.37	21	21
LCK	-0.089	0.22	-9999	-0.55	85	85
BCL3	0	0.084	-9999	-0.5	13	13

×

S1P3 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
PDGFRB	0.011	0.041	-9999	-0.5	3	3
mol:S1P	0.002	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.023	0.07	-9999	-0.29	19	19
GNAO1	0.008	0.071	-9999	-0.61	6	6
S1P/S1P3/G12/G13	0.002	0.093	-9999	-0.28	44	44
AKT1	-0.008	0.033	-9999	-0.34	1	1
AKT3	0.027	0.14	-9999	-1.1	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.041	-9999	-0.49	3	3
GNAI2	0.016	0.002	-9999	-10000	0	0
GNAI3	0.016	0.002	-9999	-10000	0	0
GNAI1	-0.007	0.12	-9999	-0.61	17	17
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.034	0.16	-9999	-0.52	44	44
S1PR2	0.008	0.062	-9999	-0.58	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.017	0.099	-9999	-0.48	9	9
MAPK3	0.025	0.095	-9999	-0.45	9	9
MAPK1	0.025	0.095	-9999	-0.45	9	9
JAK2	0.021	0.1	-9999	-0.43	11	11
CXCR4	0.01	0.12	-9999	-0.37	24	24
FLT1	0.016	0.03	-9999	-0.62	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.025	0.095	-9999	-0.45	9	9
S1P/S1P3/Gi	0.017	0.1	-9999	-0.49	9	9
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.022	0.077	-9999	-0.44	9	9
VEGFA	-0.006	0.11	-9999	-0.49	21	21
S1P/S1P2/Gi	0.029	0.078	-9999	-0.46	6	6
VEGFR1 homodimer/VEGFA homodimer	0.013	0.081	-9999	-0.35	22	22
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.012	0.11	-9999	-0.3	47	47
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.015	0.029	-9999	-0.61	1	1
G12/G13	-0.001	0.02	-9999	-0.44	1	1
GNA14	-0.018	0.13	-9999	-0.58	25	25
GNA15	-0.01	0.12	-9999	-0.58	19	19
GNA12	0.013	0.029	-9999	-0.61	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.005	0.076	-9999	-0.61	7	7
Rac1/GTP	-0.022	0.077	-9999	-0.44	9	9

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.003	0.082	0.58	9	-10000	0	9
PI3K Class IB/PDE3B	0.003	0.082	-10000	0	-0.58	9	9
PDE3B	0.003	0.083	-10000	0	-0.58	9	9

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.032	0.089	-10000	0	-0.55	6	6
CLOCK	-0.016	0.14	-10000	0	-0.6	25	25
TIMELESS/CRY2	0.025	0.085	-10000	0	-0.65	1	1
DEC1/BMAL1	-0.006	0.06	-10000	0	-0.35	14	14
ATR	0.014	0	-10000	0	-10000	0	0
NR1D1	0.027	0.11	-10000	0	-1.4	2	2
ARNTL	0.014	0.042	-10000	0	-0.5	3	3
TIMELESS	0.025	0.083	-10000	0	-10000	0	0
NPAS2	0.006	0.082	-10000	0	-0.57	9	9
CRY2	0.009	0.057	-10000	0	-0.61	4	4
mol:CO	-0.012	0.019	0.081	15	-10000	0	15
CHEK1	0.008	0.058	-10000	0	-0.5	6	6
mol:HEME	0.012	0.019	-10000	0	-0.081	15	15
PER1	0.001	0.09	-10000	0	-0.61	10	10
BMAL/CLOCK/NPAS2	0.014	0.11	-10000	0	-0.37	32	32
BMAL1/CLOCK	0.017	0.13	-10000	0	-0.71	5	5
S phase of mitotic cell cycle	0.032	0.089	-10000	0	-0.55	6	6
TIMELESS/CHEK1/ATR	0.033	0.09	-10000	0	-0.55	6	6
mol:NADPH	0.012	0.019	-10000	0	-0.081	15	15
PER1/TIMELESS	0.021	0.093	-10000	0	-0.65	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.003	0.077	-10000	0	-0.5	11	11

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.052	0.22	-10000	0	-0.9	22	22
oxygen homeostasis	0.008	0.018	-10000	0	-10000	0	0
TCEB2	0.014	0	-10000	0	-10000	0	0
TCEB1	0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.005	0.049	-10000	0	-0.33	4	4
EPO	0.095	0.24	-10000	0	-0.7	14	14
FIH (dimer)	0.022	0.017	-10000	0	-10000	0	0
APEX1	0.021	0.017	-10000	0	-10000	0	0
SERPINE1	0.014	0.34	-10000	0	-0.73	32	32
FLT1	-0.003	0.1	-10000	0	-0.95	4	4
ADORA2A	0.095	0.24	-10000	0	-0.72	13	13
germ cell development	0.078	0.26	-10000	0	-0.71	18	18
SLC11A2	0.097	0.24	-10000	0	-0.73	13	13
BHLHE40	0.086	0.26	-10000	0	-0.78	18	18
HIF1AN	0.022	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.024	0.088	-10000	0	-0.45	9	9
ETS1	0.021	0.077	-10000	0	-0.56	8	8
CITED2	0.002	0.039	-10000	0	-0.45	1	1
KDR	-0.009	0.12	-10000	0	-0.75	10	10
PGK1	0.097	0.24	-10000	0	-0.73	13	13
SIRT1	0.015	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.1	0.28	-10000	0	-0.89	14	14
EPAS1	0.07	0.12	-10000	0	-0.38	6	6
SP1	0.019	0.017	-10000	0	-10000	0	0
ABCG2	0.096	0.25	-10000	0	-0.78	13	13
EFNA1	0.096	0.24	-10000	0	-0.73	14	14
FXN	0.096	0.24	-10000	0	-0.72	13	13
POU5F1	0.077	0.27	-10000	0	-0.74	19	19
neuron apoptosis	-0.1	0.27	0.84	14	-10000	0	14
EP300	0.009	0.057	-10000	0	-0.61	4	4
EGLN3	0.011	0.084	-10000	0	-0.61	8	8
EGLN2	0.022	0.017	-10000	0	-10000	0	0
EGLN1	0.022	0.017	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.02	0.031	-10000	0	-0.52	1	1
SLC2A1	0.095	0.24	-10000	0	-0.73	13	13
TWIST1	0.069	0.28	-10000	0	-0.76	23	23
ELK1	0.023	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.024	0.089	-10000	0	-0.45	9	9
VEGFA	0.088	0.26	-10000	0	-0.78	17	17
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.012	0.033	-10000	0	-0.5	2	2
mol:Halofuginone	0.005	0.011	-10000	0	-0.23	1	1
ITGA1	-0.009	0.11	-10000	0	-0.52	20	20
CDKN1A	-0.024	0.12	-10000	0	-0.41	24	24
PRL-3/alpha Tubulin	-0.003	0.032	-10000	0	-0.35	4	4
mol:Ca2+	-0.017	0.089	0.23	2	-0.44	19	21
AGT	-0.011	0.12	-10000	0	-0.6	19	19
CCNA2	-0.057	0.16	-10000	0	-0.53	14	14
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	-0.061	0.17	-10000	0	-0.38	100	100
CDK2/Cyclin E1	-0.014	0.12	-10000	0	-0.41	23	23
MAPK3	0.022	0.034	-10000	0	-0.35	4	4
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.034	-10000	0	-0.35	4	4
PTP4A1	-0.028	0.14	-10000	0	-0.96	1	1
PTP4A3	0.01	0.047	-10000	0	-0.5	4	4
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.02	0.042	-10000	0	-0.35	6	6
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.005	0.062	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.023	0.13	-10000	0	-0.91	1	1
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.001	0.03	0.23	4	-0.46	1	5
RHOC	0.004	0.064	-10000	0	-0.33	2	2
RHOA	0.005	0.062	-10000	0	-0.28	1	1
cell motility	0.008	0.066	-10000	0	-0.3	1	1
PRL-1/alpha Tubulin	-0.019	0.13	-10000	0	-0.91	1	1
PRL-3/alpha1 Integrin	-0.019	0.084	-10000	0	-0.38	23	23
ROCK1	0.008	0.066	-10000	0	-0.3	1	1
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	-0.001	0.092	-10000	0	-0.54	13	13
mitosis	-0.028	0.14	-10000	0	-0.95	1	1
ATF5	0.007	0.062	-10000	0	-0.5	7	7

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.087	0.14	-10000	0	-0.36	71	71
Ran/GTP/Exportin 1/HDAC1	-0.002	0.022	-10000	0	-0.27	3	3
NF kappa B1 p50/RelA/I kappa B alpha	-0.035	0.14	-10000	0	-0.52	2	2
SUMO1	0.014	0	-10000	0	-10000	0	0
ZFPM1	0.013	0.029	-10000	0	-0.61	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-10000	0	-10000	0	0
FKBP3	0.014	0	-10000	0	-10000	0	0
Histones	-0.039	0.066	-10000	0	-0.44	3	3
YY1/LSF	0.031	0.032	-10000	0	-0.35	1	1
SMG5	0.014	0	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.042	0.12	-10000	0	-0.45	2	2
I kappa B alpha/HDAC1	-0.024	0.094	-10000	0	-0.39	5	5
SAP18	0.014	0	-10000	0	-10000	0	0
RELA	-0.032	0.11	-10000	0	-0.25	71	71
HDAC1/Smad7	-0.002	0.03	-10000	0	-0.37	3	3
RANGAP1	0.014	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.022	0.087	-10000	0	-0.3	2	2
NuRD/MBD3 Complex	0.051	0.02	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.022	0.1	-10000	0	-0.35	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.006	0.11	-10000	0	-0.58	16	16
GATA1	0.004	0.058	-10000	0	-0.5	6	6
Mad/Max	0	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.06	0.027	-10000	0	-10000	0	0
RBBP7	0.014	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0.014	0	-10000	0	-10000	0	0
MAX	0.014	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
NFKBIA	-0.033	0.098	-10000	0	-0.34	2	2
KAT2B	0.013	0.024	-10000	0	-0.5	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.046	0.023	-10000	0	-10000	0	0
SIN3 complex	-0.001	0.015	-10000	0	-0.33	1	1
SMURF1	0.014	0	-10000	0	-10000	0	0
CHD3	0.013	0.029	-10000	0	-0.61	1	1
SAP30	0.013	0.029	-10000	0	-0.61	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.013	0.029	-10000	0	-0.61	1	1
YY1/HDAC3	-0.007	0.085	-10000	0	-0.3	3	3
YY1/HDAC2	0.032	0.026	-10000	0	-0.24	4	4
YY1/HDAC1	0.029	0.04	-10000	0	-0.29	7	7
NuRD/MBD2 Complex (MeCP1)	0.051	0.02	-10000	0	-10000	0	0
PPARG	-0.092	0.14	-10000	0	-0.36	82	82
HDAC8/hEST1B	-0.001	0.017	-10000	0	-0.37	1	1
UBE2I	0.014	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-10000	0	-10000	0	0
TNFRSF1A	0.003	0.079	-10000	0	-0.56	9	9
HDAC3/SMRT (N-CoR2)	-0.022	0.087	-10000	0	-0.3	2	2
MBD3L2	0	0.001	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.002	0.029	-10000	0	-0.37	3	3
CREBBP	0.014	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.055	0.021	-10000	0	-10000	0	0
HDAC1	0.01	0.05	-10000	0	-0.61	3	3
HDAC3	-0.033	0.098	-10000	0	-0.34	2	2
HDAC2	0.014	0	-10000	0	-10000	0	0
YY1	0.031	0.031	-10000	0	-0.29	4	4
HDAC8	0.013	0.029	-10000	0	-0.61	1	1
SMAD7	0.014	0	-10000	0	-10000	0	0
NCOR2	0.014	0	-10000	0	-10000	0	0
MXD1	0.014	0	-10000	0	-10000	0	0
STAT3	0.025	0.035	-10000	0	-0.35	4	4
NFKB1	0.014	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.014	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.035	0.041	-10000	0	-0.32	4	4
YY1/SAP30/HDAC1	0.035	0.041	-10000	0	-0.32	4	4
EP300	0.009	0.057	-10000	0	-0.61	4	4
STAT3 (dimer non-phopshorylated)	0.025	0.035	-10000	0	-0.35	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.033	0.098	-10000	0	-0.34	2	2
histone deacetylation	0.051	0.02	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.011	0.086	-10000	0	-0.36	2	2
nuclear export	0.001	0.017	0.37	1	-10000	0	1
PRKACA	0.014	0	-10000	0	-10000	0	0
GATAD2B	0.014	0	-10000	0	-10000	0	0
GATAD2A	0.014	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.033	0.11	-10000	0	-0.39	13	13
GATA1/HDAC1	-0.007	0.053	-10000	0	-0.38	9	9
GATA1/HDAC3	-0.033	0.089	-10000	0	-0.35	3	3
CHD4	0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.13	0.19	-10000	0	-0.4	149	149
SIN3/HDAC complex/Mad/Max	0.051	0.02	-10000	0	-10000	0	0
NuRD Complex	0.06	0.021	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.038	0.065	-10000	0	-0.44	3	3
SIN3B	0.014	0	-10000	0	-10000	0	0
MTA2	0.014	0	-10000	0	-10000	0	0
SIN3A	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.031	0.027	-10000	0	-0.3	3	3
HDAC complex	-0.002	0.026	-10000	0	-0.33	3	3
GATA1/Fog1	-0.005	0.044	-10000	0	-0.36	7	7
FKBP25/HDAC1/HDAC2	-0.002	0.03	-10000	0	-0.37	3	3
TNF	-0.16	0.26	-10000	0	-0.55	142	142
negative regulation of cell growth	0.051	0.02	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.051	0.02	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.045	0.14	-10000	0	-0.34	71	71
SIN3/HDAC complex/NCoR1	0.048	0.022	-10000	0	-10000	0	0
TFCP2	0.013	0.029	-10000	0	-0.61	1	1
NR2C1	0.014	0	-10000	0	-10000	0	0
MBD3	0.014	0	-10000	0	-10000	0	0
MBD2	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.049	0.13	-9999	-0.37	61	61
AKT1	0.077	0.079	-9999	-0.58	2	2
PTK2B	-0.003	0.15	-9999	-0.5	20	20
VEGFR2 homodimer/Frs2	0.031	0.074	-9999	-0.47	8	8
CAV1	-0.048	0.17	-9999	-0.5	56	56
CALM1	0.012	0.037	-9999	-0.55	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.019	0.082	-9999	-0.67	4	4
endothelial cell proliferation	0.062	0.1	-9999	-0.47	4	4
mol:Ca2+	0.038	0.094	-9999	-0.6	4	4
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.019	0.084	-9999	-0.64	5	5
RP11-342D11.1	0.028	0.093	-9999	-0.61	4	4
CDH5	0.011	0.041	-9999	-0.5	3	3
VEGFA homodimer	-0.012	0.053	-9999	-10000	0	0
SHC1	0.009	0.053	-9999	-0.5	5	5
SHC2	0.013	0.029	-9999	-0.61	1	1
HRAS/GDP	-0.019	0.074	-9999	-0.53	5	5
SH2D2A	-0.074	0.2	-9999	-0.54	73	73
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.022	0.073	-9999	-0.48	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.06	0.14	-9999	-0.6	12	12
VEGFR1 homodimer	0.013	0.029	-9999	-0.61	1	1
SHC/GRB2/SOS1	-0.021	0.083	-9999	-0.52	8	8
GRB10	0.037	0.1	-9999	-0.57	6	6
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.024	-9999	-0.5	1	1
PAK1	-0.036	0.16	-9999	-0.51	45	45
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.019	0.088	-9999	-0.71	5	5
HRAS	0.014	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.026	0.081	-9999	-0.4	4	4
HIF1A	0.013	0.024	-9999	-0.5	1	1
FRS2	0.012	0.037	-9999	-0.55	2	2
oxygen and reactive oxygen species metabolic process	-0.019	0.083	-9999	-0.64	5	5
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.004	0.076	-9999	-0.53	9	9
Nck/Pak	-0.036	0.11	-9999	-0.36	46	46
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.018	0.081	-9999	-0.67	4	4
mol:GDP	-0.021	0.08	-9999	-0.51	8	8
mol:NADP	0.062	0.084	-9999	-0.41	7	7
eNOS/Hsp90	0.066	0.08	-9999	-0.42	4	4
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.038	0.095	-9999	-0.61	4	4
HIF1A/ARNT	-0.001	0.023	-9999	-0.35	2	2
SHB	0.014	0	-9999	-10000	0	0
VEGFA	-0.006	0.11	-9999	-0.49	21	21
VEGFC	-0.002	0.095	-9999	-0.54	14	14
FAK1/Vinculin	0.034	0.12	-9999	-0.64	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.048	0.12	-9999	-0.52	19	19
PTPN6	-0.003	0.099	-9999	-0.56	14	14
EPAS1	0.02	0.053	-9999	-0.63	2	2
mol:L-citrulline	0.062	0.084	-9999	-0.41	7	7
ITGAV	0.013	0.029	-9999	-0.61	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.018	0.078	-9999	-0.63	4	4
VEGFR2 homodimer/VEGFA homodimer	-0.023	0.088	-9999	-0.66	4	4
VEGFR2/3 heterodimer	0.026	0.094	-9999	-0.55	9	9
VEGFB	0.014	0	-9999	-10000	0	0
MAPK11	0.039	0.099	-9999	-0.6	5	5
VEGFR2 homodimer	0.031	0.08	-9999	-0.56	7	7
FLT1	0.013	0.029	-9999	-0.61	1	1
NEDD4	0.006	0.077	-9999	-0.54	9	9
MAPK3	0.03	0.1	-9999	-0.51	5	5
MAPK1	0.03	0.1	-9999	-0.51	5	5
VEGFA145/NRP2	-0.023	0.09	-9999	-0.37	28	28
VEGFR1/2 heterodimer	0.031	0.073	-9999	-0.47	8	8
KDR	0.031	0.08	-9999	-0.56	7	7
VEGFA165/NRP1/VEGFR2 homodimer	0.031	0.1	-9999	-0.57	5	5
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.032	0.1	-9999	-0.53	5	5
PI3K	0.064	0.09	-9999	-0.6	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.018	0.082	-9999	-0.67	4	4
FES	0.036	0.1	-9999	-0.59	5	5
GAB1	-0.017	0.077	-9999	-0.63	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.018	0.081	-9999	-0.67	4	4
CTNNB1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.013	0.024	-9999	-0.5	1	1
eNOS/Caveolin-1	0.04	0.12	-9999	-0.48	6	6
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.02	0.084	-9999	-0.67	4	4
PI3K/GAB1	0.078	0.083	-9999	-0.55	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.036	0.093	-9999	-0.6	5	5
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.02	0.096	-9999	-0.69	6	6
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.038	0.096	-9999	-0.62	4	4
actin cytoskeleton reorganization	-0.06	0.13	-9999	-0.59	12	12
PTK2	0.031	0.12	-9999	-0.62	5	5
EDG1	0.028	0.093	-9999	-0.61	4	4
mol:DAG	0.038	0.095	-9999	-0.61	4	4
CaM/Ca2+	-0.019	0.072	-9999	-0.56	4	4
MAP2K3	0.038	0.11	-9999	-0.59	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.037	0.1	-9999	-0.59	6	6
PLCG1	0.038	0.096	-9999	-0.62	4	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.016	0.075	-9999	-0.63	4	4
IQGAP1	0.007	0.062	-9999	-0.53	6	6
YES1	0.01	0.05	-9999	-0.61	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.018	0.081	-9999	-0.67	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.026	0.096	-9999	-0.62	6	6
cell migration	0.059	0.12	-9999	-0.62	6	6
mol:PI-3-4-5-P3	0.062	0.085	-9999	-0.55	3	3
FYN	0.014	0	-9999	-10000	0	0
VEGFB/NRP1	0.035	0.089	-9999	-0.57	4	4
mol:NO	0.062	0.084	-9999	-0.41	7	7
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.019	0.074	-9999	-0.53	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.037	0.1	-9999	-0.59	6	6
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.055	0.18	-9999	-0.52	60	60
NOS3	0.063	0.091	-9999	-0.46	7	7
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.018	0.085	-9999	-0.66	5	5
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.045	0.091	-9999	-0.56	4	4
PRKCB	0.005	0.14	-9999	-0.51	16	16
VCL	0.006	0.068	-9999	-0.54	7	7
VEGFA165/NRP1	0.028	0.094	-9999	-0.61	4	4
VEGFR1/2 heterodimer/VEGFA homodimer	-0.018	0.082	-9999	-0.67	4	4
VEGFA165/NRP2	-0.023	0.09	-9999	-0.37	28	28
MAPKKK cascade	0.059	0.098	-9999	-0.57	5	5
NRP2	0.004	0.078	-9999	-0.58	8	8
VEGFC homodimer	-0.002	0.094	-9999	-0.53	14	14
NCK1	0.013	0.029	-9999	-0.61	1	1
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.037	0.11	-9999	-0.61	4	4
MAP3K13	0.031	0.11	-9999	-0.6	5	5
PDPK1	0.068	0.079	-9999	-0.55	2	2

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.034	0.038	-9999	-0.74	1	1
VEGFR1 homodimer/NRP1	0.023	0.038	-9999	-0.74	1	1
mol:DAG	-0.018	0.13	-9999	-0.67	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.013	0.062	-9999	-0.69	1	1
CaM/Ca2+	-0.01	0.13	-9999	-0.59	2	2
HIF1A	0.021	0.029	-9999	-0.41	2	2
GAB1	0.012	0.037	-9999	-0.55	2	2
AKT1	0.008	0.12	-9999	-0.58	1	1
PLCG1	-0.018	0.13	-9999	-0.67	1	1
NOS3	0.008	0.13	-9999	-0.49	3	3
CBL	0.014	0	-9999	-10000	0	0
mol:NO	0.009	0.12	-9999	-0.47	3	3
FLT1	0.032	0.044	-9999	-0.84	1	1
PGF	-0.091	0.22	-9999	-0.56	84	84
VEGFR1 homodimer/NRP2/VEGFR121	0.022	0.083	-9999	-0.59	2	2
CALM1	0.012	0.037	-9999	-0.55	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
eNOS/Hsp90	0.016	0.12	-9999	-0.5	2	2
endothelial cell proliferation	-0.032	0.16	-9999	-0.53	16	16
mol:Ca2+	-0.018	0.13	-9999	-0.66	1	1
MAPK3	0.001	0.12	-9999	-0.58	1	1
MAPK1	0.001	0.12	-9999	-0.58	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
PLGF homodimer	-0.091	0.22	-9999	-0.56	84	84
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.048	0.17	-9999	-0.5	56	56
VEGFA homodimer	-0.009	0.11	-9999	-0.49	21	21
VEGFR1 homodimer/VEGFA homodimer	0.02	0.075	-9999	-0.74	1	1
platelet activating factor biosynthetic process	0.009	0.12	-9999	-0.56	1	1
PI3K	-0.05	0.11	-9999	-0.64	1	1
PRKCA	-0.008	0.12	-9999	-0.62	1	1
PRKCB	-0.05	0.16	-9999	-0.56	15	15
VEGFR1 homodimer/PLGF homodimer	-0.033	0.15	-9999	-0.37	53	53
VEGFA	-0.009	0.11	-9999	-0.5	21	21
VEGFB	0.014	0	-9999	-10000	0	0
mol:IP3	-0.018	0.13	-9999	-0.67	1	1
RASA1	0.042	0.036	-9999	-0.67	1	1
NRP2	0.004	0.078	-9999	-0.58	8	8
VEGFR1 homodimer	0.031	0.044	-9999	-0.83	1	1
VEGFB homodimer	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.029	-9999	-0.61	1	1
eNOS/Caveolin-1	-0.013	0.14	-9999	-0.48	7	7
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.049	0.11	-9999	-0.63	1	1
mol:L-citrulline	0.009	0.12	-9999	-0.47	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.012	0.055	-9999	-0.64	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.027	0.071	-9999	-0.68	1	1
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.047	0.099	-9999	-0.6	1	1
PDPK1	-0.001	0.12	-9999	-0.59	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.028	0.069	-9999	-0.68	1	1
mol:NADP	0.009	0.12	-9999	-0.47	3	3
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.012	0.054	-9999	-0.63	1	1
VEGFR1 homodimer/NRP2	0.027	0.062	-9999	-0.42	7	7

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.05	-9999	-0.61	3	3
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.008	0.054	-9999	-0.37	10	10
forebrain development	-0.005	0.16	-9999	-0.44	37	37
GNAO1	0.006	0.071	-9999	-0.61	6	6
SMO/beta Arrestin2	0.016	0.053	-9999	-0.44	6	6
SMO	0.006	0.07	-9999	-0.61	6	6
ARRB2	0.014	0.004	-9999	-10000	0	0
GLI3/SPOP	0.04	0.069	-9999	-0.61	1	1
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.014	0	-9999	-10000	0	0
GNAI2	0.014	0.003	-9999	-10000	0	0
SIN3/HDAC complex	0.003	0.02	-9999	-0.33	1	1
GNAI1	-0.008	0.12	-9999	-0.61	17	17
XPO1	0.016	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.042	0.1	-9999	-0.52	11	11
SAP30	0.013	0.029	-9999	-0.61	1	1
mol:GDP	0.006	0.07	-9999	-0.6	6	6
MIM/GLI2A	0.01	0.063	-9999	-0.59	5	5
IFT88	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0.002	-9999	-10000	0	0
GLI2	0.044	0.036	-9999	-10000	0	0
GLI3	0.034	0.072	-9999	-0.64	1	1
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0	-9999	-10000	0	0
GNG2	0.009	0.057	-9999	-0.61	4	4
Gi family/GTP	0.022	0.074	-9999	-0.3	13	13
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.054	0.054	-9999	-0.44	1	1
GLI2/Su(fu)	0.056	0.046	-9999	-10000	0	0
FOXA2	-0.04	0.14	-9999	-0.7	9	9
neural tube patterning	-0.005	0.16	-9999	-0.44	37	37
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.029	0.042	-9999	-0.32	4	4
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
CSNK1G3	0.014	0	-9999	-10000	0	0
MTSS1	0.01	0.063	-9999	-0.59	5	5
embryonic limb morphogenesis	-0.005	0.16	-9999	-0.44	37	37
SUFU	0.028	0.029	-9999	-10000	0	0
LGALS3	-0.024	0.14	-9999	-0.5	34	34
catabolic process	0.064	0.065	-9999	-0.5	1	1
GLI3A/CBP	-0.017	0.11	-9999	-0.35	29	29
KIF3A	0.013	0.029	-9999	-0.61	1	1
GLI1	-0.006	0.16	-9999	-0.45	37	37
RAB23	0.013	0.029	-9999	-0.61	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	0.01	0.05	-9999	-0.61	3	3
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.011	0.082	-9999	-0.43	3	3
GNAZ	0.013	0.029	-9999	-0.61	1	1
RBBP4	0.014	0.001	-9999	-10000	0	0
CSNK1G1	0.013	0.024	-9999	-0.5	1	1
PIAS1	0.009	0.057	-9999	-0.61	4	4
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.048	0.033	-9999	-10000	0	0
STK36	0.015	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.028	0.076	-9999	-0.47	4	4
PTCH1	-0.006	0.19	-9999	-0.96	11	11
MIM/GLI1	-0.007	0.18	-9999	-0.55	23	23
CREBBP	-0.017	0.1	-9999	-0.35	29	29
Su(fu)/SIN3/HDAC complex	0.053	0.026	-9999	-0.29	1	1

×

Arf6 downstream 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
PLAUR	0.014	0.13	-10000	0	-1.1	2	2
regulation of axonogenesis	-0.005	0.07	0.22	31	-10000	0	31
myoblast fusion	-0.003	0.062	0.41	2	-10000	0	2
mol:GTP	-0.011	0.036	-10000	0	-0.23	2	2
regulation of calcium-dependent cell-cell adhesion	-0.027	0.042	0.35	1	-10000	0	1
ARF1/GTP	-0.006	0.023	-10000	0	-10000	0	0
mol:GM1	0.004	0.03	-10000	0	-0.18	2	2
mol:Choline	-0.006	0.1	-10000	0	-0.33	39	39
lamellipodium assembly	-0.017	0.057	-10000	0	-0.45	2	2
MAPK3	0.017	0.057	-10000	0	-0.34	2	2
ARF6/GTP/NME1/Tiam1	0.027	0.043	-10000	0	-0.35	1	1
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	0.003	0.062	-10000	0	-0.42	2	2
ARF1/GDP	0.013	0.057	-10000	0	-0.38	2	2
ARF6	0.007	0.021	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.014	0.029	-10000	0	-0.61	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.057	-10000	0	-0.34	2	2
actin filament bundle formation	-0.012	0.057	0.38	2	-10000	0	2
KALRN	-0.018	0.057	-10000	0	-0.24	16	16
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0.012	0.057	-10000	0	-0.38	2	2
NME1	0.015	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.012	0.057	-10000	0	-0.38	2	2
substrate adhesion-dependent cell spreading	-0.011	0.036	-10000	0	-0.23	2	2
cortical actin cytoskeleton organization	-0.017	0.058	-10000	0	-0.45	2	2
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.011	0.036	-10000	0	-0.23	2	2
ARF6/GTP	-0.011	0.036	-10000	0	-0.23	2	2
RhoA/GTP	-0.006	0.023	-10000	0	-10000	0	0
mol:GDP	-0.017	0.057	-10000	0	-0.42	2	2
ARF6/GTP/RAB11FIP3/RAB11A	-0.004	0.017	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	-0.02	0.12	-10000	0	-0.39	39	39
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.017	0.057	-10000	0	-0.45	2	2
ruffle organization	0.005	0.07	-10000	0	-0.22	31	31
regulation of epithelial cell migration	-0.011	0.036	-10000	0	-0.23	2	2
PLD2	0.015	0.03	-10000	0	-10000	0	0
PIP5K1A	0.005	0.07	-10000	0	-0.22	31	31
mol:Phosphatidic acid	-0.006	0.1	-10000	0	-0.33	39	39
Rac1/GTP	-0.017	0.058	-10000	0	-0.45	2	2

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.012	0.058	-9999	-0.59	1	1
TC10/GTP	-0.009	0.051	-9999	-0.57	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.031	-9999	-0.31	4	4
HRAS	0.014	0	-9999	-10000	0	0
APS homodimer	-0.001	0.094	-9999	-0.58	12	12
GRB14	-0.18	0.27	-9999	-0.54	164	164
FOXO3	-0.025	0.091	-9999	-0.59	11	11
AKT1	-0.039	0.13	-9999	-0.44	4	4
INSR	0.016	0.002	-9999	-10000	0	0
Insulin Receptor/Insulin	0.037	0.027	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0.037	-9999	-0.55	2	2
SORBS1	0.009	0.057	-9999	-0.61	4	4
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.036	0.027	-9999	-10000	0	0
CAV1	-0.006	0.099	-9999	-0.43	6	6
CBL/APS/CAP/Crk-II/C3G	-0.01	0.057	-9999	-0.62	1	1
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.031	-9999	-0.31	4	4
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.026	-9999	-0.29	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.033	-9999	-10000	0	0
RPS6KB1	-0.027	0.12	-9999	-0.4	4	4
PARD6A	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.039	-9999	-0.83	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.064	0.091	-9999	-0.41	4	4
HRAS/GTP	-0.007	0.039	-9999	-0.43	1	1
Insulin Receptor	0.016	0.002	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.006	0.038	-9999	-0.31	1	1
PRKCI	-0.023	0.057	-9999	-0.56	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.082	0.11	-9999	-0.48	4	4
SHC1	0.009	0.053	-9999	-0.5	5	5
negative regulation of MAPKKK cascade	-0.001	0.037	-9999	-0.51	2	2
PI3K	-0.003	0.026	-9999	-0.3	1	1
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.039	0.13	-9999	-0.44	4	4
PRKCZ	-0.046	0.12	-9999	-0.6	20	20
SH2B2	-0.001	0.095	-9999	-0.58	12	12
SHC/SHIP	0.029	0.053	-9999	-0.35	4	4
F2RL2	-0.098	0.22	-9999	-0.52	97	97
TRIP10	0.006	0.07	-9999	-0.56	7	7
Insulin Receptor/Insulin/Shc	-0.005	0.039	-9999	-0.28	8	8
TC10/GTP/CIP4/Exocyst	-0.005	0.042	-9999	-0.34	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.005	0.035	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.029	-9999	-0.61	1	1
CBL/APS/CAP/Crk-II	-0.011	0.061	-9999	-0.36	12	12
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.007	0.042	-9999	-0.31	4	4
INPP5D	0.024	0.048	-9999	-0.34	6	6
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.026	0.14	-9999	-0.89	11	11
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.013	0.029	-9999	-0.61	1	1
p62DOK/RasGAP	-0.001	0.037	-9999	-0.52	2	2
INS	-0.001	0.054	-9999	-0.57	4	4
mol:PI-3-4-P2	0.024	0.047	-9999	-0.34	6	6
GRB2	0.013	0.024	-9999	-0.5	1	1
EIF4EBP1	-0.034	0.13	-9999	-0.43	12	12
PTPRA	0.016	0.002	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
TC10/GTP/CIP4	-0.005	0.042	-9999	-0.34	7	7
PDPK1	0.013	0.029	-9999	-0.61	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.033	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.032	-9999	-0.32	4	4
Insulin Receptor/Insulin/IRS3	-0.004	0.038	-9999	-0.41	4	4
Par3/Par6	-0.056	0.11	-9999	-0.32	28	28

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.02	0.075	-9999	-0.37	10	10
PDGFB-D/PDGFRB/SLAP	-0.017	0.1	-9999	-0.4	30	30
PDGFB-D/PDGFRB/APS/CBL	-0.01	0.064	-9999	-0.37	12	12
AKT1	0.06	0.036	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.008	0.087	-9999	-0.37	10	10
PIK3CA	0.014	0	-9999	-10000	0	0
FGR	0.001	0.029	-9999	-10000	0	0
mol:Ca2+	0.018	0.042	-9999	-10000	0	0
MYC	-0.002	0.19	-9999	-0.81	22	22
SHC1	0.009	0.053	-9999	-0.5	5	5
HRAS/GDP	0.019	0.028	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.001	0.023	-9999	-0.28	1	1
GRB10	0.012	0.037	-9999	-0.55	2	2
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0.018	0.042	-9999	-10000	0	0
PTEN	0.013	0.029	-9999	-0.61	1	1
GRB2	0.013	0.024	-9999	-0.5	1	1
GRB7	-0.031	0.14	-9999	-0.5	38	38
PDGFB-D/PDGFRB/SHP2	0.007	0.03	-9999	-0.34	3	3
PDGFB-D/PDGFRB/GRB10	0.006	0.04	-9999	-0.36	5	5
cell cycle arrest	-0.02	0.1	-9999	-0.4	30	30
HRAS	0.014	0	-9999	-10000	0	0
HIF1A	0.065	0.035	-9999	-10000	0	0
GAB1	0.005	0.074	-9999	-0.39	3	3
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.009	0.075	-9999	-0.39	3	3
PDGFB-D/PDGFRB	0.011	0.03	-9999	-0.29	3	3
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.007	0.03	-9999	-0.34	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.026	0.087	-9999	-0.42	11	11
positive regulation of MAPKKK cascade	0.005	0.03	-9999	-0.34	3	3
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.018	0.043	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.014	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.021	0.1	-9999	-0.36	40	40
SHB	0.014	0	-9999	-10000	0	0
BLK	-0.054	0.13	-9999	-0.54	27	27
PTPN2	0.014	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.007	0.03	-9999	-0.34	3	3
BCAR1	0.013	0.029	-9999	-0.61	1	1
VAV2	0.006	0.089	-9999	-0.39	7	7
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.006	0.04	-9999	-0.36	5	5
LCK	-0.058	0.15	-9999	-0.53	40	40
PDGFRB	0.011	0.041	-9999	-0.5	3	3
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.011	0.097	-9999	-0.62	10	10
ABL1	0.007	0.063	-9999	-0.32	4	4
PDGFB-D/PDGFRB/CBL	0.005	0.071	-9999	-0.4	2	2
PTPN1	0.014	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.002	0.09	-9999	-0.5	15	15
cell proliferation	0.002	0.17	-9999	-0.7	22	22
SLA	-0.02	0.14	-9999	-0.55	28	28
actin cytoskeleton reorganization	0.048	0.034	-9999	-10000	0	0
SRC	0.002	0.026	-9999	-10000	0	0
PI3K	-0.004	0.03	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.027	0.093	-9999	-0.69	2	2
SH2B2	-0.001	0.095	-9999	-0.58	12	12
PLCgamma1/SPHK1	0.008	0.089	-9999	-0.38	10	10
LYN	-0.002	0.053	-9999	-0.64	2	2
LRP1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
STAT5B	0.014	0	-9999	-10000	0	0
STAT5A	0	0.093	-9999	-0.6	11	11
NCK1-2/p130 Cas	0.004	0.031	-9999	-10000	0	0
SPHK1	-0.028	0.15	-9999	-0.55	35	35
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.018	0.043	-9999	-10000	0	0
PLCG1	0.019	0.043	-9999	-10000	0	0
NHERF/PDGFRB	-0.004	0.042	-9999	-0.33	6	6
YES1	-0.001	0.053	-9999	-0.56	3	3
cell migration	-0.005	0.042	-9999	-0.33	6	6
SHC/Grb2/SOS1	0.002	0.041	-9999	-0.46	2	2
SLC9A3R2	0.012	0.033	-9999	-0.5	2	2
SLC9A3R1	0.01	0.05	-9999	-0.61	3	3
NHERF1-2/PDGFRB/PTEN	0.001	0.043	-9999	-0.33	4	4
FYN	0.003	0.027	-9999	-10000	0	0
DOK1	0.032	0.03	-9999	-0.34	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.014	0	-9999	-10000	0	0
RAC1	0.01	0.12	-9999	-0.43	23	23
PRKCD	0.016	0.082	-9999	-0.34	22	22
FER	0.019	0.075	-9999	-0.33	18	18
MAPKKK cascade	-0.004	0.036	-9999	-0.45	2	2
RASA1	0.034	0.025	-9999	-10000	0	0
NCK1	0.013	0.029	-9999	-0.61	1	1
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	0.022	0.033	-9999	-0.3	1	1
PDGFB-D/PDGFRB/SHB	0.007	0.03	-9999	-0.34	3	3
chemotaxis	0.007	0.062	-9999	-0.31	4	4
STAT1-3-5/STAT1-3-5	-0.014	0.057	-9999	-0.44	1	1
Bovine Papilomavirus E5/PDGFRB	0.007	0.03	-9999	-0.36	3	3
PTPRJ	0.012	0.037	-9999	-0.55	2	2

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.003	0.03	-9999	-0.33	4	4
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.004	0.039	-9999	-0.35	6	6
GATA1/HDAC5	-0.004	0.039	-9999	-0.35	6	6
GATA2/HDAC5	-0.014	0.076	-9999	-0.42	16	16
HDAC5/BCL6/BCoR	-0.001	0.013	-9999	-0.28	1	1
HDAC9	0.001	0.087	-9999	-0.56	11	11
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
GATA2	-0.006	0.11	-9999	-0.58	16	16
HDAC4/RFXANK	-0.001	0.016	-9999	-0.35	1	1
BCOR	0.013	0.024	-9999	-0.5	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	-0.004	0.041	-9999	-0.44	4	4
Histones	0.04	0.031	-9999	-10000	0	0
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.014	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.016	-9999	-0.35	1	1
CAMK4	-0.17	0.28	-9999	-0.58	145	145
Tubulin/HDAC6	-0.001	0.017	-9999	-0.37	1	1
SUMO1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
GATA1	0.004	0.058	-9999	-0.5	6	6
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.034	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.02	-9999	-0.44	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.016	-9999	-0.35	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.11	0.16	-9999	-0.35	145	145
HDAC4/ER alpha	-0.02	0.088	-9999	-0.39	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.04	0.031	-9999	-10000	0	0
cell motility	-0.001	0.017	-9999	-0.37	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.015	0.13	-9999	-0.55	24	24
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.008	0.11	-9999	-0.51	20	20
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.01	0.047	-9999	-0.3	2	2
GNG2	0.009	0.057	-9999	-0.61	4	4
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.013	0.029	-9999	-0.61	1	1
HDAC11	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.014	0	-9999	-10000	0	0
RFXANK	0.013	0.024	-9999	-0.5	1	1
nuclear import	-0.032	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.012	0.17	-9999	-1.4	5	5
PLK1	0.05	0.22	-9999	-1.1	7	7
CDKN1B	0.1	0.12	-9999	-10000	0	0
FOXO3	0.065	0.16	-9999	-0.59	6	6
KAT2B	0.022	0.027	-9999	-0.48	1	1
FOXO1/SIRT1	-0.005	0.07	-9999	-0.41	5	5
CAT	0.068	0.16	-9999	-0.92	2	2
CTNNB1	0.014	0	-9999	-10000	0	0
AKT1	0.025	0.017	-9999	-10000	0	0
FOXO1	0.026	0.085	-9999	-0.35	12	12
MAPK10	0.038	0.036	-9999	-0.32	4	4
mol:GTP	0.002	0.002	-9999	-10000	0	0
FOXO4	0.097	0.065	-9999	-10000	0	0
response to oxidative stress	0.011	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	0.014	0.14	-9999	-0.54	6	6
XPO1	0.015	0.001	-9999	-10000	0	0
EP300	0.01	0.058	-9999	-0.61	4	4
BCL2L11	0.031	0.1	-9999	-1.4	2	2
FOXO1/SKP2	0.024	0.093	-9999	-0.41	12	12
mol:GDP	0.011	0.02	-9999	-10000	0	0
RAN	0.016	0.001	-9999	-10000	0	0
GADD45A	0.082	0.14	-9999	-1	1	1
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.042	0.073	-9999	-0.31	1	1
MST1	-0.021	0.16	-9999	-0.57	34	34
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.1	-9999	-0.52	1	1
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.034	0.054	-9999	-0.31	10	10
MAPK9	0.041	0.014	-9999	-10000	0	0
YWHAG	0.001	0.081	-9999	-0.5	12	12
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.01	0.011	-9999	-10000	0	0
SOD2	0.095	0.16	-9999	-0.74	2	2
RBL2	0.087	0.12	-9999	-10000	0	0
RAL/GDP	0.03	0.017	-9999	-10000	0	0
CHUK	0.023	0.014	-9999	-10000	0	0
Ran/GTP	0.014	0.005	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
RAL/GTP	0.038	0.019	-9999	-10000	0	0
CSNK1G1	0.013	0.024	-9999	-0.5	1	1
FASLG	0.001	0.11	-9999	-0.36	35	35
SKP2	0.004	0.076	-9999	-0.56	8	8
USP7	0.016	0.001	-9999	-10000	0	0
IKBKB	0.023	0.014	-9999	-10000	0	0
CCNB1	0.058	0.18	-9999	-0.73	3	3
FOXO1-3a-4/beta catenin	0.12	0.13	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.092	-9999	-0.41	12	12
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.007	0.099	-9999	-0.59	12	12
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.009	-9999	-10000	0	0
ZFAND5	0.099	0.058	-9999	-10000	0	0
SFN	-0.12	0.23	-9999	-0.53	109	109
CDK2	-0.001	0.092	-9999	-0.54	13	13
FOXO3A/14-3-3	0.022	0.094	-9999	-0.44	1	1
CREBBP	0.014	0.013	-9999	-10000	0	0
FBXO32	0.057	0.19	-9999	-1.1	4	4
BCL6	0.087	0.12	-9999	-10000	0	0
RALB	0.016	0.001	-9999	-10000	0	0
RALA	0.016	0.001	-9999	-10000	0	0
YWHAH	-0.01	0.11	-9999	-0.5	22	22

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.067	0.2	-9999	-0.56	65	65
CLTC	0.031	0.015	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.016	0.046	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0.014	0	-9999	-10000	0	0
CD59	0.026	0.021	-9999	-10000	0	0
CPE	0.005	0.076	-9999	-0.37	18	18
CTNNB1	0.014	0	-9999	-10000	0	0
membrane fusion	0.015	0.049	-9999	-10000	0	0
CTNND1	0.035	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.029	0.026	-9999	-10000	0	0
TSHR	-0.12	0.18	-9999	-0.34	182	182
INS	0.007	0.044	-9999	-0.52	3	3
BIN1	0.014	0	-9999	-10000	0	0
mol:Choline	0.015	0.049	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.021	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.021	0.043	-9999	-0.3	4	4
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	-0.019	0.09	-9999	-0.3	11	11
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0.014	0	-9999	-10000	0	0
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.014	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.048	0.006	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.026	0.051	-9999	-10000	0	0
positive regulation of phagocytosis	0.021	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0	0	-9999	-10000	0	0
ACAP1	0.013	0.043	-9999	-0.29	1	1
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.02	0.085	-9999	-0.3	4	4
clathrin heavy chain/ACAP1	0.032	0.03	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.014	0	-9999	-10000	0	0
exocyst	0.048	0.006	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0.035	0	-9999	-10000	0	0
NME1	0.021	0	-9999	-10000	0	0
clathrin coat assembly	0.031	0.015	-9999	-10000	0	0
IL2RA	0.002	0.06	-9999	-10000	0	0
VAMP3	0.021	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.038	0.086	-9999	-0.28	39	39
EXOC6	0.014	0	-9999	-10000	0	0
PLD1	-0.021	0.073	-9999	-0.29	31	31
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.014	0	-9999	-10000	0	0
PIP5K1C	0.029	0.026	-9999	-10000	0	0
SDC1	0.012	0.049	-9999	-10000	0	0
ARF6/GDP	0.02	0	-9999	-10000	0	0
EXOC7	0.013	0.024	-9999	-0.5	1	1
E-cadherin/beta catenin	-0.027	0.053	-9999	-10000	0	0
mol:Phosphatidic acid	0.015	0.049	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.014	0	-9999	-10000	0	0
ADRB2	0.021	0.077	-9999	-0.3	24	24
EXOC3	0.014	0	-9999	-10000	0	0
ASAP2	0.014	0	-9999	-10000	0	0
Dynamin 2/GDP	0.028	0	-9999	-10000	0	0
KLC1	0.014	0	-9999	-10000	0	0
AVPR2	0.026	0.056	-9999	-0.26	5	5
RALA	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.045	-9999	-10000	0	0

×

IGF1 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
NCK2	0.014	0	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
CRKL	0.018	0.058	-9999	-0.3	12	12
GRB2/SOS1/SHC	-0.004	0.032	-9999	-0.28	6	6
HRAS	0.014	0	-9999	-10000	0	0
IRS1/Crk	0.018	0.058	-9999	-0.3	12	12
IGF-1R heterotetramer/IGF1/PTP1B	-0.013	0.062	-9999	-0.34	12	12
AKT1	0.039	0.053	-9999	-10000	0	0
BAD	0.046	0.05	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.018	0.058	-9999	-0.3	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.017	0.058	-9999	-0.3	12	12
RAF1	0.05	0.05	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.025	0.057	-9999	-0.28	12	12
YWHAZ	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.009	0.063	-9999	-0.32	13	13
PIK3CA	0.014	0	-9999	-10000	0	0
RPS6KB1	0.039	0.053	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.043	0.044	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	-0.001	0.016	-9999	-0.35	1	1
HRAS/GTP	-0.011	0.049	-9999	-0.36	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.013	0.057	-9999	-0.44	2	2
IGF-1R heterotetramer	0.011	0.027	-9999	-0.48	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	0.018	0.058	-9999	-0.3	12	12
Crk/p130 Cas/Paxillin	-0.01	0.046	-9999	-10000	0	0
IGF1R	0.011	0.027	-9999	-0.48	1	1
IGF1	-0.008	0.11	-9999	-0.57	18	18
IRS2/Crk	0.025	0.06	-9999	-0.48	1	1
PI3K	0.026	0.055	-9999	-0.27	12	12
apoptosis	-0.05	0.045	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.016	0.12	-9999	-0.56	12	12
RAF1/14-3-3 E	0.054	0.045	-9999	-10000	0	0
BAD/14-3-3	0.052	0.047	-9999	-10000	0	0
PRKCZ	0.023	0.085	-9999	-0.44	2	2
Crk/p130 Cas/Paxillin/FAK1	-0.007	0.034	-9999	-10000	0	0
PTPN1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.024	0.075	-9999	-0.4	12	12
BCAR1	0.013	0.029	-9999	-0.61	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.015	0.065	-9999	-0.44	3	3
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
IRS1/NCK2	0.018	0.058	-9999	-0.3	12	12
GRB10	0.012	0.037	-9999	-0.55	2	2
PTPN11	0.018	0.058	-9999	-0.3	12	12
IRS1	0.009	0.063	-9999	-0.32	13	13
IRS2	0.017	0.063	-9999	-0.31	13	13
IGF-1R heterotetramer/IGF1	0.002	0.086	-9999	-0.41	19	19
GRB2	0.013	0.024	-9999	-0.5	1	1
PDPK1	0.032	0.055	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
PRKD1	0.032	0.072	-9999	-0.38	12	12
SHC1	0.009	0.053	-9999	-0.5	5	5

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.017	-10000	0	-0.35	1	1
BAD/BCL-XL/YWHAZ	0.036	0.013	-10000	0	-10000	0	0
CDKN1B	0.041	0.006	-10000	0	-10000	0	0
CDKN1A	0.007	0.093	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
FOXO3	0.041	0.006	-10000	0	-10000	0	0
AKT1	0	0.005	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
AKT3	0.015	0.051	-10000	0	-0.49	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.04	0.016	-10000	0	-10000	0	0
AKT1/ASK1	-0.003	0.029	-10000	0	-0.31	4	4
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.014	0	-10000	0	-10000	0	0
RAF1	0.014	0	-10000	0	-10000	0	0
JNK cascade	0.003	0.028	0.3	4	-10000	0	4
TSC1	0.041	0.006	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
AKT1/RAF1	0.041	0.006	-10000	0	-10000	0	0
EP300	0.009	0.057	-10000	0	-0.61	4	4
mol:GDP	0.034	0.007	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.041	0.006	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.026	0.015	-10000	0	-0.3	1	1
MAP3K5	0.009	0.057	-10000	0	-0.61	4	4
MAPKAP1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.013	0.06	0.28	1	-10000	0	1
YWHAH	-0.01	0.11	-10000	0	-0.5	22	22
AKT1S1	0.041	0.006	-10000	0	-10000	0	0
CASP9	0.041	0.013	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.048	0.006	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.017	-10000	0	-0.37	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0
SRC	0.014	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.028	0.075	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.002	-10000	0	-10000	0	0
CHUK	0.041	0.006	-10000	0	-10000	0	0
BAD/BCL-XL	0.055	0.013	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.018	0.018	-10000	0	-0.36	1	1
FOXO1-3a-4/14-3-3 family	0.03	0.065	-10000	0	-0.29	1	1
PDPK1	0.013	0.029	-10000	0	-0.61	1	1
MDM2	0.04	0.018	-10000	0	-10000	0	0
MAPKKK cascade	-0.04	0.006	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.051	0.035	-10000	0	-0.38	1	1
TSC1/TSC2	0.048	0.006	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.028	-10000	0	-0.36	1	1
glucose import	-0.013	0.12	-10000	0	-0.32	40	40
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.035	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.013	0.12	-10000	0	-0.33	40	40
GSK3A	0.041	0.006	-10000	0	-10000	0	0
FOXO1	0.039	0.025	-10000	0	-10000	0	0
GSK3B	0.041	0.006	-10000	0	-10000	0	0
SFN	-0.12	0.23	-10000	0	-0.53	109	109
G1/S transition of mitotic cell cycle	0.048	0.006	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.006	0.087	-10000	0	-0.39	3	3
PRKACA	0.014	0	-10000	0	-10000	0	0
KPNA1	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
YWHAG	0.001	0.081	-10000	0	-0.5	12	12
RHEB	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Alternative NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.037	-9999	-0.48	1	1
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.004	0.038	-9999	-0.36	5	5
RELB	0.009	0.055	-9999	-0.52	5	5
NFKB2	0.011	0.047	-9999	-0.57	3	3
NF kappa B2 p52/RelB	-0.006	0.046	-9999	-0.37	7	7
regulation of B cell activation	-0.006	0.046	-9999	-0.37	7	7

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.014	0	-9999	-10000	0	0
SMAD2	0.016	0.018	-9999	-0.25	1	1
SMAD3	0.044	0.019	-9999	-10000	0	0
SMAD3/SMAD4	0.051	0.01	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.015	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.012	0.037	-9999	-0.55	2	2
SMAD2/SMAD4	0.023	0.016	-9999	-10000	0	0
MAP3K1	0.009	0.053	-9999	-0.5	5	5
TRAP-1/SMAD4	-0.013	0.075	-9999	-0.44	14	14
MAPK3	0.014	0	-9999	-10000	0	0
MAPK1	0.014	0	-9999	-10000	0	0
NUP214	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
CTDSP2	0.01	0.047	-9999	-0.5	4	4
CTDSPL	0.013	0.029	-9999	-0.61	1	1
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	-0.004	0.11	-9999	-0.61	14	14
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.012	0.033	-9999	-0.5	2	2
PIAS4	0.014	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.009	0.057	-10000	0	-0.61	4	4
mol:PIP3	0	0.019	0.29	1	-0.29	1	2
FRAP1	0.017	0.008	-10000	0	-10000	0	0
AKT1	0.031	0.02	0.23	1	-10000	0	1
INSR	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.033	-10000	0	-0.36	4	4
mol:GTP	-0.001	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.003	-10000	0	-10000	0	0
TSC2	0.014	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.01	-10000	0	-10000	0	0
TSC1	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.017	0.017	-10000	0	-0.36	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.031	0.013	-10000	0	-10000	0	0
MAP3K5	0.008	0.037	-10000	0	-0.39	4	4
PIK3R1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.008	0.037	-10000	0	-0.39	4	4
mol:LY294002	0	0	-10000	0	-0.002	1	1
EIF4B	0.037	0.012	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.01	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.002	0.017	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.026	0.016	-10000	0	-0.32	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.035	0.01	0.17	1	-10000	0	1
FKBP1A	0.015	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.01	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.002	1	1
FKBP12/Rapamycin	0.011	0.001	-10000	0	-10000	0	0
PDPK1	-0.001	0.021	0.24	1	-0.28	2	3
EIF4E	0.014	0	-10000	0	-10000	0	0
ASK1/PP5C	0.019	0.059	-10000	0	-0.61	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.012	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.002	1	-10000	0	1
RPS6	0.013	0.024	-10000	0	-0.5	1	1
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.009	0.019	-10000	0	-0.39	1	1
INS	-0.005	0.054	-10000	0	-0.58	4	4
PTEN	0.012	0.029	-10000	0	-0.6	1	1
PDK2	-0.001	0.021	0.24	1	-0.28	2	3
EIF4EBP1	-0.006	0.14	-10000	0	-1.1	7	7
PIK3CA	0.014	0	-10000	0	-10000	0	0
PPP2R5D	0.024	0.007	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.031	-10000	0	-0.31	4	4
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-10000	0	1
EEF2	0.016	0.031	-10000	0	-0.31	4	4
eIF4E/4E-BP1	0.003	0.13	-10000	0	-1	7	7

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.01	0.05	-9999	-0.61	3	3
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.032	0.017	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.002	0.02	-9999	-0.25	3	3
SUMO1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.032	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.034	0	-9999	-10000	0	0
SUMO1/HDAC1	0.031	0.027	-9999	-0.3	3	3
RANGAP1	0.014	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.004	0.034	-9999	-0.33	4	4
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	0	-9999	-10000	0	0
Ran/GTP	0.03	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.012	0.033	-9999	-0.5	2	2
UBE2I	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.014	0	-9999	-10000	0	0
PIAS1	0.009	0.057	-9999	-0.61	4	4
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 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
coatomer protein complex	0	0.01	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.023	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	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-10000	0	0
CD4	0.006	0.066	-9999	-0.53	7	7
CLTA	0.014	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.012	0.017	-9999	-0.36	1	1
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	0.03	0.012	-9999	-0.22	1	1
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.015	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.011	-9999	-0.24	1	1
AP2M1	0.014	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.019	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.027	0.013	-9999	-0.24	1	1
ARFIP2	0.012	0	-9999	-10000	0	0
COPA	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.029	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	0.007	-9999	-10000	0	0
ARF1/GDP/Membrin	0.02	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.015	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	0.037	0.022	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.012	0.017	-9999	-0.36	1	1
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	0.012	0.017	-9999	-0.36	1	1
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	-0.005	0.038	-9999	-0.31	7	7

pid_entity	TCGA.VW.A7QS	TCGA.TQ.A7RW	TCGA.TQ.A7RV	TCGA.TQ.A7RU
109_MAP3K5	-0.16	0.06	-0.16	-0.22
47_PPARGC1A	0.014	0.014	0.014	0.014
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	0.014	0.014	0.014
131_RELN/VLDLR	-0.59	0	0	-0.33
30_TGFB1/TGF beta receptor Type II	0.014	0.014	0.014	0.014
84_STAT5B	-0.03	0.12	0.052	-0.08
84_STAT5A	-0.18	0.12	0.052	-0.08