PARADIGM pathway analysis of mRNASeq expression data - Thyroid Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	249
Signaling events mediated by Stem cell factor receptor (c-Kit)	164
Signaling events regulated by Ret tyrosine kinase	149
TCGA08_retinoblastoma	142
Reelin signaling pathway	125
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	115
IL4-mediated signaling events	111
Wnt signaling	105
PDGFR-alpha signaling pathway	98
Noncanonical Wnt signaling pathway	93

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Ephrin A reverse signaling	0.5102	249	1749	7	-0.52	0	1000	-1000	-0.034	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3361	164	12800	78	-0.8	0.24	1000	-1000	-0.067	-1000
Signaling events regulated by Ret tyrosine kinase	0.3053	149	12241	82	-0.46	0.013	1000	-1000	-0.081	-1000
TCGA08_retinoblastoma	0.2910	142	1141	8	-0.13	0.073	1000	-1000	-0.016	-1000
Reelin signaling pathway	0.2561	125	7027	56	-0.6	0.033	1000	-1000	-0.083	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2357	115	7820	68	-0.89	0.37	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.2275	111	10139	91	-1.3	0.66	1000	-1000	-0.12	-1000
Wnt signaling	0.2152	105	740	7	-0.41	0.013	1000	-1000	-0.02	-1000
PDGFR-alpha signaling pathway	0.2008	98	4336	44	-0.5	0.033	1000	-1000	-0.052	-1000
Noncanonical Wnt signaling pathway	0.1906	93	2427	26	-0.41	0.013	1000	-1000	-0.082	-1000
FOXA2 and FOXA3 transcription factor networks	0.1783	87	4030	46	-0.92	0.021	1000	-1000	-0.057	-1000
Nongenotropic Androgen signaling	0.1762	86	4512	52	-0.34	0.16	1000	-1000	-0.058	-1000
Signaling events mediated by the Hedgehog family	0.1619	79	4115	52	-0.38	0.2	1000	-1000	-0.083	-1000
Calcium signaling in the CD4+ TCR pathway	0.1516	74	2309	31	-0.52	0.013	1000	-1000	-0.089	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1496	73	2497	34	-0.17	0.013	1000	-1000	-0.054	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1475	72	3902	54	-0.6	0.028	1000	-1000	-0.1	-1000
Glypican 1 network	0.1311	64	3095	48	-0.38	0.028	1000	-1000	-0.044	-1000
Ephrin B reverse signaling	0.1291	63	3042	48	-0.31	0.19	1000	-1000	-0.072	-1000
Endothelins	0.1250	61	5928	96	-0.39	0.013	1000	-1000	-0.077	-1000
HIF-1-alpha transcription factor network	0.1209	59	4502	76	-0.56	0.042	1000	-1000	-0.091	-1000
IGF1 pathway	0.1189	58	3332	57	-0.2	0.06	1000	-1000	-0.094	-1000
Glucocorticoid receptor regulatory network	0.1107	54	6217	114	-0.56	0.37	1000	-1000	-0.07	-1000
IL23-mediated signaling events	0.1107	54	3264	60	-0.33	0.019	1000	-1000	-0.14	-1000
TCR signaling in naïve CD8+ T cells	0.1086	53	5020	93	-0.19	0.087	1000	-1000	-0.073	-1000
Glypican 2 network	0.1086	53	213	4	-0.088	-0.01	1000	-1000	-0.038	-1000
Arf6 signaling events	0.1025	50	3148	62	-0.32	0.021	1000	-1000	-0.067	-1000
BMP receptor signaling	0.1025	50	4102	81	-0.57	0.026	1000	-1000	-0.09	-1000
EPHB forward signaling	0.1025	50	4306	85	-0.31	0.15	1000	-1000	-0.086	-1000
Coregulation of Androgen receptor activity	0.0984	48	3692	76	-0.77	0.061	1000	-1000	-0.049	-1000
Syndecan-1-mediated signaling events	0.0943	46	1578	34	-0.2	0.013	1000	-1000	-0.059	-1000
IL6-mediated signaling events	0.0820	40	3051	75	-0.2	0.059	1000	-1000	-0.074	-1000
IL12-mediated signaling events	0.0779	38	3311	87	-0.4	0.022	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	0.0779	38	2496	65	-0.66	0.061	1000	-1000	-0.066	-1000
Signaling mediated by p38-alpha and p38-beta	0.0779	38	1673	44	-0.23	0.013	1000	-1000	-0.046	-1000
Syndecan-4-mediated signaling events	0.0779	38	2611	67	-0.24	0.015	1000	-1000	-0.091	-1000
amb2 Integrin signaling	0.0738	36	2993	82	-0.24	0.013	1000	-1000	-0.073	-1000
Ras signaling in the CD4+ TCR pathway	0.0717	35	599	17	-0.093	0.013	1000	-1000	-0.032	-1000
Thromboxane A2 receptor signaling	0.0676	33	3498	105	-0.22	0.032	1000	-1000	-0.07	-1000
EGFR-dependent Endothelin signaling events	0.0676	33	697	21	-0.11	0.013	1000	-1000	-0.062	-1000
TCGA08_p53	0.0615	30	210	7	-0.085	0.054	1000	-1000	-0.015	-1000
Osteopontin-mediated events	0.0594	29	1124	38	-0.26	0.013	1000	-1000	-0.11	-1000
FAS signaling pathway (CD95)	0.0594	29	1385	47	-0.26	0.03	1000	-1000	-0.047	-1000
Regulation of Androgen receptor activity	0.0553	27	1947	70	-0.48	0.034	1000	-1000	-0.062	-1000
Syndecan-2-mediated signaling events	0.0533	26	1843	69	-0.22	0.038	1000	-1000	-0.051	-1000
Regulation of p38-alpha and p38-beta	0.0533	26	1442	54	-0.47	0.013	1000	-1000	-0.055	-1000
Plasma membrane estrogen receptor signaling	0.0533	26	2277	86	-0.18	0.02	1000	-1000	-0.08	-1000
Visual signal transduction: Rods	0.0533	26	1364	52	-0.2	0.016	1000	-1000	-0.077	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0512	25	2197	85	-0.28	0.013	1000	-1000	-0.071	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0512	25	1321	52	-0.28	0.054	1000	-1000	-0.069	-1000
IL27-mediated signaling events	0.0512	25	1277	51	-0.17	0.066	1000	-1000	-0.063	-1000
ErbB2/ErbB3 signaling events	0.0492	24	1609	65	-0.13	0.027	1000	-1000	-0.066	-1000
JNK signaling in the CD4+ TCR pathway	0.0492	24	411	17	-0.1	0.02	1000	-1000	-0.052	-1000
LPA receptor mediated events	0.0492	24	2502	102	-0.25	0.031	1000	-1000	-0.08	-1000
BCR signaling pathway	0.0492	24	2473	99	-0.19	0.023	1000	-1000	-0.083	-1000
Integrins in angiogenesis	0.0471	23	1993	84	-0.24	0.034	1000	-1000	-0.091	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0471	23	2107	88	-0.32	0.028	1000	-1000	-0.11	-1000
Signaling events mediated by PTP1B	0.0430	21	1660	76	-0.24	0.021	1000	-1000	-0.073	-1000
Fc-epsilon receptor I signaling in mast cells	0.0430	21	2054	97	-0.2	0.03	1000	-1000	-0.076	-1000
VEGFR1 specific signals	0.0430	21	1205	56	-0.069	0.041	1000	-1000	-0.068	-1000
Aurora C signaling	0.0410	20	140	7	-0.06	0	1000	-1000	-0.041	-1000
Regulation of nuclear SMAD2/3 signaling	0.0389	19	2689	136	-0.34	0.066	1000	-1000	-0.07	-1000
Nectin adhesion pathway	0.0389	19	1230	63	-0.26	0.032	1000	-1000	-0.078	-1000
Visual signal transduction: Cones	0.0369	18	704	38	-0.089	0.013	1000	-1000	-0.064	-1000
p75(NTR)-mediated signaling	0.0369	18	2273	125	-0.35	0.066	1000	-1000	-0.099	-1000
IL1-mediated signaling events	0.0369	18	1166	62	-0.12	0.066	1000	-1000	-0.092	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0369	18	2185	120	-0.31	0.042	1000	-1000	-0.083	-1000
FOXM1 transcription factor network	0.0369	18	939	51	-0.18	0.049	1000	-1000	-0.16	-1000
ErbB4 signaling events	0.0348	17	1179	69	-0.14	0.056	1000	-1000	-0.092	-1000
Syndecan-3-mediated signaling events	0.0348	17	629	35	-0.16	0.013	1000	-1000	-0.068	-1000
TCGA08_rtk_signaling	0.0348	17	452	26	-0.24	0.025	1000	-1000	-0.018	-1000
Rapid glucocorticoid signaling	0.0328	16	326	20	-0.09	0.014	1000	-1000	-0.04	-1000
Aurora B signaling	0.0328	16	1098	67	-0.38	0.014	1000	-1000	-0.073	-1000
LPA4-mediated signaling events	0.0307	15	189	12	-0.12	0.015	1000	-1000	-0.02	-1000
Presenilin action in Notch and Wnt signaling	0.0307	15	934	61	-0.2	0.042	1000	-1000	-0.068	-1000
Effects of Botulinum toxin	0.0307	15	399	26	-0.16	0.019	1000	-1000	-0.059	-1000
IL2 signaling events mediated by STAT5	0.0307	15	332	22	-0.069	0.039	1000	-1000	-0.049	-1000
Insulin Pathway	0.0307	15	1127	74	-0.087	0.038	1000	-1000	-0.08	-1000
Insulin-mediated glucose transport	0.0287	14	478	32	-0.21	0.042	1000	-1000	-0.064	-1000
IFN-gamma pathway	0.0287	14	965	68	-0.1	0.042	1000	-1000	-0.084	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0287	14	467	33	-0.16	0.035	1000	-1000	-0.056	-1000
Signaling events mediated by PRL	0.0287	14	485	34	-0.11	0.013	1000	-1000	-0.038	-1000
Class IB PI3K non-lipid kinase events	0.0287	14	42	3	-0.003	-1000	1000	-1000	-0.013	-1000
Ceramide signaling pathway	0.0266	13	1006	76	-0.18	0.024	1000	-1000	-0.061	-1000
Signaling events mediated by HDAC Class III	0.0266	13	548	40	-0.35	0.024	1000	-1000	-0.046	-1000
IL2 signaling events mediated by PI3K	0.0266	13	783	58	-0.067	0.031	1000	-1000	-0.084	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0246	12	349	28	-0.18	0.031	1000	-1000	-0.061	-1000
a4b1 and a4b7 Integrin signaling	0.0246	12	62	5	-0.031	0.002	1000	-1000	-0.039	-1000
mTOR signaling pathway	0.0246	12	640	53	-0.047	0.02	1000	-1000	-0.056	-1000
BARD1 signaling events	0.0225	11	637	57	-0.035	0.052	1000	-1000	-0.068	-1000
Cellular roles of Anthrax toxin	0.0225	11	437	39	-0.09	0.019	1000	-1000	-0.033	-1000
Class I PI3K signaling events	0.0225	11	813	73	-0.24	0.023	1000	-1000	-0.054	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0205	10	870	83	-0.21	0.052	1000	-1000	-0.076	-1000
Retinoic acid receptors-mediated signaling	0.0205	10	584	58	-0.12	0.032	1000	-1000	-0.07	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0205	10	451	45	-0.09	0.039	1000	-1000	-0.085	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0205	10	806	74	-0.18	0.085	1000	-1000	-0.091	-1000
Caspase cascade in apoptosis	0.0184	9	703	74	-0.09	0.029	1000	-1000	-0.053	-1000
Regulation of Telomerase	0.0184	9	964	102	-0.28	0.053	1000	-1000	-0.099	-1000
Class I PI3K signaling events mediated by Akt	0.0164	8	566	68	-0.21	0.052	1000	-1000	-0.064	-1000
ceramide signaling pathway	0.0164	8	421	49	-0.09	0.031	1000	-1000	-0.043	-1000
S1P3 pathway	0.0164	8	367	42	-0.18	0.048	1000	-1000	-0.062	-1000
TRAIL signaling pathway	0.0143	7	371	48	-0.077	0.047	1000	-1000	-0.068	-1000
S1P1 pathway	0.0143	7	257	36	-0.037	0.031	1000	-1000	-0.062	-1000
Signaling events mediated by HDAC Class I	0.0143	7	734	104	-0.09	0.059	1000	-1000	-0.062	-1000
Canonical Wnt signaling pathway	0.0143	7	370	51	-0.049	0.067	1000	-1000	-0.068	-1000
Canonical NF-kappaB pathway	0.0123	6	248	39	-0.09	0.071	1000	-1000	-0.076	-1000
Circadian rhythm pathway	0.0123	6	149	22	-0.057	0.013	1000	-1000	-0.055	-1000
Arf6 downstream pathway	0.0123	6	285	43	-0.18	0.094	1000	-1000	-0.041	-1000
FoxO family signaling	0.0123	6	419	64	-0.21	0.16	1000	-1000	-0.057	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0102	5	216	37	-0.032	0.039	1000	-1000	-0.062	-1000
Atypical NF-kappaB pathway	0.0102	5	159	31	-0.043	0.047	1000	-1000	-0.05	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0102	5	668	125	-0.035	0.085	1000	-1000	-0.082	-1000
E-cadherin signaling in the nascent adherens junction	0.0102	5	382	76	-0.17	0.074	1000	-1000	-0.084	-1000
EPO signaling pathway	0.0082	4	242	55	-0.037	0.061	1000	-1000	-0.089	-1000
PLK1 signaling events	0.0061	3	285	85	-0.04	0.033	1000	-1000	-0.044	-1000
S1P5 pathway	0.0061	3	62	17	-0.017	0.022	1000	-1000	-0.059	-1000
HIF-2-alpha transcription factor network	0.0061	3	142	43	-0.2	0.2	1000	-1000	-0.065	-1000
Signaling mediated by p38-gamma and p38-delta	0.0061	3	52	15	0	0.031	1000	-1000	-0.029	-1000
Paxillin-dependent events mediated by a4b1	0.0061	3	140	36	-0.031	0.024	1000	-1000	-0.078	-1000
PDGFR-beta signaling pathway	0.0061	3	368	97	-0.18	0.064	1000	-1000	-0.078	-1000
p38 MAPK signaling pathway	0.0061	3	150	44	-0.04	0.026	1000	-1000	-0.062	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0041	2	65	23	-0.04	0.049	1000	-1000	-0.065	-1000
Signaling events mediated by HDAC Class II	0.0041	2	178	75	-0.047	0.036	1000	-1000	-0.057	-1000
PLK2 and PLK4 events	0.0041	2	6	3	0.009	0.022	1000	-1000	-0.011	-1000
Aurora A signaling	0.0041	2	165	60	-0.048	0.038	1000	-1000	-0.062	-1000
E-cadherin signaling in keratinocytes	0.0041	2	127	43	-0.004	0.053	1000	-1000	-0.066	-1000
S1P4 pathway	0.0041	2	67	25	-0.017	0.032	1000	-1000	-0.058	-1000
Arf6 trafficking events	0.0020	1	80	71	-0.023	0.046	1000	-1000	-0.078	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.056	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.044	-1000
Arf1 pathway	0.0000	0	36	54	-0.005	0.035	1000	-1000	-0.053	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.063	-1000
Total	NA	4089	224414	7203	-30	-990	131000	-131000	-8.7	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.42	0.31	-9999	-0.61	341	341
EFNA5	-0.11	0.3	-9999	-0.81	75	75
FYN	-0.38	0.3	-9999	-0.56	341	341
neuron projection morphogenesis	-0.42	0.31	-9999	-0.61	341	341
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.43	0.31	-9999	-0.61	341	341
EPHA5	-0.52	0.4	-9999	-0.82	310	310

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.22	0.22	-10000	0	-0.4	285	285
CRKL	-0.22	0.24	-10000	0	-0.42	278	278
HRAS	-0.19	0.21	-10000	0	-0.5	46	46
mol:PIP3	-0.22	0.22	-10000	0	-0.41	278	278
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.012	0.038	-10000	0	-0.82	1	1
GAB1	-0.24	0.25	-10000	0	-0.45	278	278
FOXO3	-0.19	0.22	-10000	0	-0.38	278	278
AKT1	-0.22	0.23	-10000	0	-0.42	278	278
BAD	-0.19	0.22	-10000	0	-0.38	278	278
megakaryocyte differentiation	-0.25	0.25	-10000	0	-0.45	286	286
GSK3B	-0.19	0.22	-10000	0	-0.38	278	278
RAF1	-0.15	0.18	-10000	0	-0.4	40	40
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.24	0.25	-10000	0	-0.45	278	278
STAT1	-0.6	0.59	-10000	0	-1.1	280	280
HRAS/SPRED1	-0.18	0.14	-10000	0	-0.39	45	45
cell proliferation	-0.24	0.26	-10000	0	-0.45	281	281
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.24	0.25	-10000	0	-0.45	278	278
HRAS/SPRED2	-0.18	0.14	-10000	0	-0.4	46	46
LYN/TEC/p62DOK	-0.24	0.21	-10000	0	-0.41	278	278
MAPK3	-0.095	0.13	-10000	0	-0.31	24	24
STAP1	-0.26	0.25	-10000	0	-0.47	278	278
GRAP2	-0.041	0.2	-10000	0	-0.77	34	34
JAK2	-0.52	0.45	-10000	0	-0.9	280	280
STAT1 (dimer)	-0.58	0.57	-10000	0	-1.1	280	280
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.25	0.21	-10000	0	-0.42	281	281
actin filament polymerization	-0.23	0.24	-10000	0	-0.44	278	278
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.35	0.34	-10000	0	-0.64	278	278
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.21	0.19	-10000	0	-0.37	278	278
PI3K	-0.22	0.24	-10000	0	-0.42	279	279
PTEN	0.012	0.038	-10000	0	-0.82	1	1
SCF/KIT/EPO/EPOR	-0.74	0.72	-10000	0	-1.4	278	278
MAPK8	-0.25	0.26	-10000	0	-0.46	281	281
STAT3 (dimer)	-0.23	0.24	-10000	0	-0.44	278	278
positive regulation of transcription	-0.076	0.11	-10000	0	-0.25	22	22
mol:GDP	-0.23	0.19	-10000	0	-0.48	72	72
PIK3C2B	-0.24	0.25	-10000	0	-0.45	278	278
CBL/CRKL	-0.2	0.22	-10000	0	-0.39	278	278
FER	-0.24	0.25	-10000	0	-0.45	279	279
SH2B3	-0.24	0.25	-10000	0	-0.45	278	278
PDPK1	-0.2	0.21	-10000	0	-0.37	279	279
SNAI2	-0.24	0.26	-10000	0	-0.46	280	280
positive regulation of cell proliferation	-0.42	0.42	-10000	0	-0.77	280	280
KITLG	-0.006	0.11	-10000	0	-0.85	8	8
cell motility	-0.42	0.42	-10000	0	-0.77	280	280
PTPN6	0.021	0.018	-10000	0	-10000	0	0
EPOR	-0.14	0.18	-10000	0	-0.56	8	8
STAT5A (dimer)	-0.34	0.35	-10000	0	-0.63	280	280
SOCS1	0.009	0.048	-10000	0	-0.82	1	1
cell migration	0.24	0.25	0.45	281	-10000	0	281
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.005	0.041	-10000	0	-0.33	7	7
VAV1	-0.013	0.1	-10000	0	-0.36	35	35
GRB10	-0.24	0.25	-10000	0	-0.45	278	278
PTPN11	0.02	0.038	-10000	0	-0.8	1	1
SCF/KIT	-0.26	0.26	-10000	0	-0.48	278	278
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.11	0.14	-10000	0	-0.35	24	24
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.8	0.75	-10000	0	-1.4	278	278
MAP2K2	-0.11	0.14	-10000	0	-0.35	24	24
SHC/Grb2/SOS1	-0.24	0.21	-10000	0	-0.41	278	278
STAT5A	-0.35	0.36	-10000	0	-0.65	280	280
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.24	0.25	-10000	0	-0.45	280	280
SHC/GRAP2	-0.041	0.15	-10000	0	-0.63	31	31
PTPRO	-0.26	0.25	-10000	0	-0.46	286	286
SH2B2	-0.24	0.25	-10000	0	-0.45	278	278
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.25	0.25	-10000	0	-0.46	281	281
CREBBP	0.017	0.02	-10000	0	-10000	0	0
BCL2	-0.22	0.42	-10000	0	-1.6	36	36

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.088	0.068	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.2	-9999	-0.51	119	119
JUN	-0.32	0.31	-9999	-0.68	171	171
HRAS	0.012	0.021	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.38	0.32	-9999	-0.6	302	302
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.38	0.32	-9999	-0.6	302	302
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.29	0.25	-9999	-0.51	278	278
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.34	0.29	-9999	-0.54	302	302
GRB7	-0.042	0.12	-9999	-0.31	82	82
RET51/GFRalpha1/GDNF	-0.38	0.32	-9999	-0.6	302	302
MAPKKK cascade	-0.3	0.26	-9999	-0.48	302	302
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.35	0.31	-9999	-0.58	291	291
lamellipodium assembly	-0.24	0.18	-9999	-0.38	279	279
RET51/GFRalpha1/GDNF/SHC	-0.38	0.32	-9999	-0.6	302	302
PIK3CA	0.008	0.065	-9999	-0.82	3	3
RET9/GFRalpha1/GDNF/SHC	-0.29	0.25	-9999	-0.51	278	278
RET9/GFRalpha1/GDNF/Shank3	-0.29	0.25	-9999	-0.51	278	278
MAPK3	-0.31	0.29	-9999	-0.51	302	302
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.12	0.3	-9999	-0.82	77	77
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.3	0.29	-9999	-0.67	128	128
DOK5	-0.1	0.29	-9999	-0.82	67	67
GFRA1	-0.46	0.41	-9999	-0.81	279	279
MAPK8	-0.24	0.24	-9999	-0.59	91	91
HRAS/GTP	-0.35	0.3	-9999	-0.56	302	302
tube development	-0.27	0.23	-9999	-0.47	278	278
MAPK1	-0.31	0.29	-9999	-0.51	302	302
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.18	0.18	-9999	-0.34	278	278
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
PDLIM7	0.011	0.029	-9999	-0.31	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.43	0.38	-9999	-0.66	313	313
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.38	0.32	-9999	-0.6	302	302
RET51/GFRalpha1/GDNF/Dok5	-0.45	0.38	-9999	-0.68	314	314
PRKCA	-0.026	0.18	-9999	-0.82	23	23
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
CREB1	-0.24	0.24	-9999	-0.43	278	278
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.18	0.18	-9999	-0.34	278	278
RET51/GFRalpha1/GDNF/Grb7	-0.41	0.33	-9999	-0.63	302	302
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.16	0.32	-9999	-0.64	133	133
DOK4	0.013	0.015	-9999	-0.31	1	1
JNK cascade	-0.31	0.3	-9999	-0.66	171	171
RET9/GFRalpha1/GDNF/FRS2	-0.29	0.25	-9999	-0.51	278	278
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.18	-9999	-0.34	278	278
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.25	0.24	-9999	-0.41	302	302
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.25	0.23	-9999	-0.41	302	302
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.28	0.31	-9999	-0.47	302	302
PI3K	-0.37	0.34	-9999	-0.62	280	280
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.27	0.23	-9999	-0.47	278	278
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.22	0.21	-9999	-0.38	278	278
RET51/GFRalpha1/GDNF/FRS2	-0.38	0.32	-9999	-0.6	302	302
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.087	0.27	-9999	-0.82	59	59
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.28	0.31	-9999	-0.47	302	302
RET51/GFRalpha1/GDNF/PKC alpha	-0.41	0.35	-9999	-0.64	304	304
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.002	0.043	-9999	-0.31	9	9
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.44	0.37	-9999	-0.67	314	314
Rac1/GTP	-0.29	0.23	-9999	-0.46	279	279
RET9/GFRalpha1/GDNF	-0.32	0.27	-9999	-0.56	278	278
GFRalpha1/GDNF	-0.36	0.31	-9999	-0.63	278	278

×

TCGA08_retinoblastoma

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
CDKN2B	-0.12	0.16	-10000	0	-0.31	203	203
CDKN2C	0.027	0.036	-10000	0	-0.31	3	3
CDKN2A	-0.13	0.16	-10000	0	-0.32	210	210
CCND2	0.07	0.073	0.17	144	-10000	0	144
RB1	-0.069	0.072	-10000	0	-0.17	144	144
CDK4	0.07	0.072	0.17	146	-10000	0	146
CDK6	0.073	0.078	0.18	144	-0.18	2	146
G1/S progression	0.061	0.08	0.17	145	-10000	0	145

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.001	0.013	-9999	-10000	0	0
VLDLR	-0.022	0.17	-9999	-0.82	21	21
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.01	0.033	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.42	0.26	-9999	-0.56	363	363
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.068	-9999	-0.46	11	11
AKT1	-0.24	0.17	-9999	-0.33	364	364
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
RELN/LRP8/DAB1	-0.39	0.24	-9999	-0.52	361	361
LRPAP1/LRP8	-0.026	0.12	-9999	-0.63	20	20
RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	361	361
DAB1/alpha3/beta1 Integrin	-0.34	0.23	-9999	-0.86	32	32
long-term memory	-0.36	0.24	-9999	-0.48	363	363
DAB1/LIS1	-0.35	0.23	-9999	-0.47	367	367
DAB1/CRLK/C3G	-0.34	0.23	-9999	-0.49	198	198
PIK3CA	0.008	0.065	-9999	-0.82	3	3
DAB1/NCK2	-0.36	0.24	-9999	-0.48	367	367
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.022	0.16	-9999	-0.63	27	27
CDK5R1	0.012	0.021	-9999	-0.31	2	2
RELN	-0.6	0.37	-9999	-0.82	357	357
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.42	0.26	-9999	-0.56	361	361
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.38	0.25	-9999	-0.5	363	363
MAPK8	-0.005	0.12	-9999	-0.82	11	11
RELN/VLDLR/DAB1	-0.39	0.24	-9999	-0.52	363	363
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.36	0.26	-9999	-0.5	367	367
RELN/LRP8	-0.42	0.26	-9999	-0.56	361	361
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.36	0.23	-9999	-0.49	361	361
PI3K	-0.004	0.049	-9999	-0.63	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.02	-9999	-10000	0	0
RAP1A	-0.3	0.23	-9999	-0.82	28	28
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.003	0.015	-9999	-0.31	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.14	-9999	-0.53	22	22
neuron adhesion	-0.28	0.22	-9999	-0.73	32	32
LRP8	-0.021	0.16	-9999	-0.82	20	20
GSK3B	-0.22	0.16	-9999	-0.61	17	17
RELN/VLDLR/DAB1/Fyn	-0.36	0.23	-9999	-0.49	363	363
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.36	364	364
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.033	0.088	-9999	-0.33	20	20
neuron migration	-0.3	0.22	-9999	-0.42	358	358
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.14	-9999	-0.54	22	22
RELN/VLDLR	-0.4	0.26	-9999	-0.53	367	367

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.042	0.16	-10000	0	-0.57	30	30
NFATC2	-0.24	0.38	-10000	0	-0.81	125	125
NFATC3	-0.084	0.13	-10000	0	-10000	0	0
CD40LG	-0.73	0.57	-10000	0	-1.2	262	262
ITCH	0.051	0.015	-10000	0	-10000	0	0
CBLB	0.051	0.015	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.53	0.52	-10000	0	-1.2	152	152
JUNB	0.003	0.091	-10000	0	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.015	-10000	0	-0.34	1	1
T cell anergy	0.025	0.065	-10000	0	-0.49	1	1
TLE4	-0.24	0.44	-10000	0	-0.86	137	137
Jun/NFAT1-c-4/p21SNFT	-0.66	0.61	-10000	0	-1.2	241	241
AP-1/NFAT1-c-4	-0.89	0.78	-10000	0	-1.5	266	266
IKZF1	-0.18	0.34	-10000	0	-0.74	97	97
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.81	129	129
AP-1/NFAT1	-0.42	0.48	-10000	0	-0.9	213	213
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.85	-10000	0	-1.6	231	231
EGR3	-0.58	0.75	-10000	0	-1.5	151	151
NFAT1/FOXP3	-0.22	0.33	-10000	0	-0.69	128	128
EGR1	-0.16	0.34	-10000	0	-0.82	104	104
JUN	-0.18	0.34	-10000	0	-0.82	110	110
EGR4	-0.034	0.18	-10000	0	-0.72	29	29
mol:Ca2+	0.016	0.01	-10000	0	-10000	0	0
GBP3	-0.16	0.32	-10000	0	-0.74	85	85
FOSL1	-0.03	0.12	-10000	0	-0.33	62	62
NFAT1-c-4/MAF/IRF4	-0.56	0.56	-10000	0	-1.1	242	242
DGKA	-0.16	0.29	-10000	0	-0.66	98	98
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.56	0.56	-10000	0	-1.1	243	243
CTLA4	-0.23	0.37	-10000	0	-0.8	113	113
NFAT1-c-4 (dimer)/EGR1	-0.64	0.67	-10000	0	-1.2	243	243
NFAT1-c-4 (dimer)/EGR4	-0.58	0.56	-10000	0	-1.1	246	246
FOS	-0.22	0.36	-10000	0	-0.82	128	128
IFNG	-0.43	0.54	-10000	0	-1.1	146	146
T cell activation	-0.44	0.42	-10000	0	-1	146	146
MAF	0.013	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.37	0.42	0.76	229	-10000	0	229
TNF	-0.6	0.58	-10000	0	-1.1	252	252
FASLG	-0.74	0.78	-10000	0	-1.5	243	243
TBX21	-0.036	0.18	-10000	0	-0.71	29	29
BATF3	-0.006	0.082	-10000	0	-0.33	27	27
PRKCQ	0.005	0.084	-10000	0	-0.82	5	5
PTPN1	-0.16	0.29	-10000	0	-0.67	95	95
NFAT1-c-4/ICER1	-0.55	0.56	-10000	0	-1	242	242
GATA3	-0.03	0.18	-10000	0	-0.78	27	27
T-helper 1 cell differentiation	-0.41	0.51	-10000	0	-1.1	147	147
IL2RA	-0.48	0.46	-10000	0	-1	160	160
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.29	-10000	0	-0.73	72	72
E2F1	-0.078	0.15	-10000	0	-10000	0	0
PPARG	-0.002	0.1	-10000	0	-0.82	7	7
SLC3A2	-0.16	0.29	-10000	0	-0.73	72	72
IRF4	-0.1	0.23	-10000	0	-0.45	119	119
PTGS2	-0.71	0.57	-10000	0	-1.2	253	253
CSF2	-0.77	0.53	-10000	0	-1.2	266	266
JunB/Fra1/NFAT1-c-4	-0.54	0.54	-10000	0	-1	237	237
IL4	-0.33	0.37	-10000	0	-0.87	125	125
IL5	-0.69	0.54	-10000	0	-1.1	260	260
IL2	-0.45	0.44	-10000	0	-1	143	143
IL3	-0.097	0.062	-10000	0	-10000	0	0
RNF128	0.049	0.042	-10000	0	-0.87	1	1
NFATC1	-0.37	0.43	-10000	0	-0.76	229	229
CDK4	0.22	0.25	0.6	63	-10000	0	63
PTPRK	-0.16	0.29	-10000	0	-0.66	97	97
IL8	-0.72	0.54	-10000	0	-1.2	254	254
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

IL4-mediated signaling events

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
BCL2L1	-0.59	0.44	-10000	0	-1	187	187
STAT6 (cleaved dimer)	-0.64	0.44	-10000	0	-0.96	278	278
IGHG1	-0.2	0.14	-10000	0	-0.34	107	107
IGHG3	-0.58	0.42	-10000	0	-0.92	245	245
AKT1	-0.32	0.26	-10000	0	-0.63	120	120
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.25	0.25	-10000	0	-0.66	78	78
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.66	149	149
THY1	-0.59	0.44	-10000	0	-1.1	176	176
MYB	-0.008	0.12	-10000	0	-0.63	16	16
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.41	0.31	-10000	0	-0.67	223	223
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.63	115	115
SP1	0.02	0.006	-10000	0	-10000	0	0
INPP5D	-0.003	0.072	-10000	0	-0.31	25	25
SOCS5	0.03	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.62	0.44	-10000	0	-0.97	255	255
SOCS1	-0.4	0.28	-10000	0	-0.72	137	137
SOCS3	-0.38	0.35	-10000	0	-0.96	81	81
FCER2	-0.58	0.42	-10000	0	-0.9	260	260
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.66	0.47	-10000	0	-1.1	223	223
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.61	64	64
T cell proliferation	-0.6	0.46	-10000	0	-1	219	219
IL4R/JAK1	-0.59	0.44	-10000	0	-1	199	199
EGR2	-0.93	0.72	-10000	0	-1.6	257	257
JAK2	-0.019	0.058	-10000	0	-0.85	2	2
JAK3	-0.068	0.14	-10000	0	-0.31	124	124
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.008	-10000	0	-10000	0	0
COL1A2	-0.19	0.15	-10000	0	-0.57	3	3
CCL26	-0.61	0.45	-10000	0	-1.1	196	196
IL4R	-0.63	0.46	-10000	0	-1.1	214	214
PTPN6	0.028	0.009	-10000	0	-10000	0	0
IL13RA2	-0.69	0.56	-10000	0	-1.3	192	192
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.33	0.47	-10000	0	-1.2	90	90
ARG1	-0.14	0.11	-10000	0	-10000	0	0
CBL	-0.38	0.29	-10000	0	-0.65	198	198
GTF3A	0.017	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
IL13RA1/JAK2	-0.025	0.052	-10000	0	-0.66	2	2
IRF4/BCL6	-0.3	0.43	-10000	0	-1.1	85	85
CD40LG	-0.11	0.3	-10000	0	-0.79	76	76
MAPK14	-0.39	0.31	-10000	0	-0.71	168	168
mitosis	-0.3	0.24	-10000	0	-0.6	120	120
STAT6	-0.67	0.51	-10000	0	-1.1	240	240
SPI1	0.002	0.07	-10000	0	-0.31	23	23
RPS6KB1	-0.29	0.23	-10000	0	-0.62	88	88
STAT6 (dimer)	-0.67	0.51	-10000	0	-1.1	240	240
STAT6 (dimer)/PARP14	-0.62	0.47	-10000	0	-1	239	239
mast cell activation	0.016	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.32	0.27	-10000	0	-0.64	121	121
FRAP1	-0.32	0.26	-10000	0	-0.63	120	120
LTA	-0.61	0.46	-10000	0	-1.1	198	198
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.66	0.49	1.1	240	-10000	0	240
CCL11	-0.58	0.43	-10000	0	-1	186	186
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.65	113	113
IL2RG	-0.043	0.19	-10000	0	-0.54	53	53
IL10	-0.61	0.46	-10000	0	-1.1	191	191
IRS1	-0.087	0.27	-10000	0	-0.82	59	59
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.094	-10000	0	-10000	0	0
IL5	-0.6	0.44	-10000	0	-1	189	189
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.48	0.33	-10000	0	-0.79	214	214
COL1A1	-0.26	0.23	-10000	0	-0.6	93	93
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.59	0.45	-10000	0	-1.1	163	163
IL2R gamma/JAK3	-0.081	0.18	-10000	0	-0.51	53	53
TFF3	-1.3	0.61	-10000	0	-1.6	399	399
ALOX15	-0.59	0.44	-10000	0	-1	189	189
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.51	0.36	-10000	0	-0.81	238	238
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.018	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.3	0.25	-10000	0	-0.64	93	93
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.63	120	120
PI3K	-0.33	0.28	-10000	0	-0.68	118	118
DOK2	0.001	0.076	-10000	0	-0.38	16	16
ETS1	0.03	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.24	0.21	-10000	0	-0.6	61	61
ITGB3	-0.61	0.47	-10000	0	-1.1	176	176
PIGR	-0.64	0.5	-10000	0	-1.1	202	202
IGHE	0.051	0.034	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.59	61	61
BCL6	0.012	0.038	-10000	0	-0.82	1	1
OPRM1	-0.6	0.44	-10000	0	-1.1	173	173
RETNLB	-0.6	0.44	-10000	0	-1	188	188
SELP	-0.6	0.45	-10000	0	-1	195	195
AICDA	-0.58	0.42	-10000	0	-1	198	198

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.46	304	304
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.005	0.051	-9999	-0.31	12	12
WNT4	-0.26	0.39	-9999	-0.81	162	162
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.004	0.12	-9999	-0.77	11	11
WNT11	-0.41	0.41	-9999	-0.81	251	251

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.25	0.39	-9999	-0.83	151	151
PDGF/PDGFRA/CRKL	-0.19	0.29	-9999	-0.62	151	151
positive regulation of JUN kinase activity	-0.15	0.22	-9999	-0.48	151	151
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.2	0.29	-9999	-0.63	151	151
AP1	-0.5	0.63	-9999	-1.4	135	135
mol:IP3	-0.19	0.3	-9999	-0.65	151	151
PLCG1	-0.19	0.31	-9999	-0.65	151	151
PDGF/PDGFRA/alphaV Integrin	-0.2	0.29	-9999	-0.63	152	152
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.3	-9999	-0.64	151	151
CAV3	-0.001	0.029	-9999	-0.31	4	4
CAV1	-0.009	0.13	-9999	-0.82	13	13
SHC/Grb2/SOS1	-0.15	0.22	-9999	-0.48	151	151
PDGF/PDGFRA/Shf	-0.19	0.29	-9999	-0.62	151	151
FOS	-0.45	0.61	-9999	-1.4	135	135
JUN	-0.17	0.28	-9999	-0.7	110	110
oligodendrocyte development	-0.2	0.29	-9999	-0.62	152	152
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.19	0.3	-9999	-0.65	151	151
PDGF/PDGFRA	-0.25	0.39	-9999	-0.83	151	151
actin cytoskeleton reorganization	-0.19	0.29	-9999	-0.62	151	151
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.17	0.25	-9999	-0.53	154	154
PDGF/PDGFRA/Crk/C3G	-0.16	0.25	-9999	-0.53	151	151
JAK1	-0.18	0.3	-9999	-0.62	151	151
ELK1/SRF	-0.12	0.24	-9999	-0.48	151	151
SHB	0.013	0	-9999	-10000	0	0
SHF	0.013	0.015	-9999	-10000	0	0
CSNK2A1	0.027	0.027	-9999	-10000	0	0
GO:0007205	-0.2	0.31	-9999	-0.66	151	151
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.15	0.22	-9999	-0.48	151	151
PDGF/PDGFRA/SHB	-0.19	0.29	-9999	-0.62	151	151
PDGF/PDGFRA/Caveolin-1	-0.21	0.31	-9999	-0.66	154	154
ITGAV	0.01	0.053	-9999	-0.82	2	2
ELK1	-0.18	0.28	-9999	-0.59	151	151
PIK3CA	0.008	0.065	-9999	-0.82	3	3
PDGF/PDGFRA/Crk	-0.19	0.29	-9999	-0.62	151	151
JAK-STAT cascade	-0.18	0.3	-9999	-0.62	151	151
cell proliferation	-0.19	0.29	-9999	-0.62	151	151

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.13	0.32	-9999	-0.82	85	85
GNB1/GNG2	-0.26	0.24	-9999	-0.59	125	125
mol:DAG	-0.21	0.24	-9999	-0.55	116	116
PLCG1	-0.22	0.24	-9999	-0.57	116	116
YES1	-0.25	0.26	-9999	-0.62	124	124
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.22	0.25	-9999	-0.57	118	118
MAP3K7	-0.17	0.2	-9999	-0.45	116	116
mol:Ca2+	-0.2	0.23	-9999	-0.53	118	118
mol:IP3	-0.21	0.24	-9999	-0.55	116	116
NLK	-0.01	0.01	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.19	0.22	-9999	-0.48	129	129
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.46	304	304
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.25	0.26	-9999	-0.58	141	141
GO:0007205	-0.21	0.23	-9999	-0.54	116	116
WNT6	0.005	0.051	-9999	-0.31	12	12
WNT4	-0.26	0.39	-9999	-0.81	162	162
NFAT1/CK1 alpha	-0.3	0.25	-9999	-0.62	148	148
GNG2	0.012	0.038	-9999	-0.82	1	1
WNT5A	-0.004	0.12	-9999	-0.77	11	11
WNT11	-0.41	0.41	-9999	-0.81	251	251
CDC42	-0.23	0.25	-9999	-0.59	118	118

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.51	0.54	-9999	-1.1	185	185
PCK1	-0.34	0.49	-9999	-1.5	60	60
HNF4A	-0.67	0.66	-9999	-1.3	238	238
KCNJ11	-0.48	0.54	-9999	-1.1	193	193
AKT1	-0.042	0.12	-9999	-0.41	2	2
response to starvation	-0.018	0.034	-9999	-10000	0	0
DLK1	-0.49	0.54	-9999	-1.1	175	175
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.51	0.54	-9999	-1.1	183	183
TAT	-0.2	0.22	-9999	-0.69	11	11
CEBPB	0.013	0.005	-9999	-10000	0	0
CEBPA	0.005	0.084	-9999	-0.82	5	5
TTR	-0.2	0.22	-9999	-0.78	26	26
PKLR	-0.52	0.54	-9999	-1.1	186	186
APOA1	-0.92	0.89	-9999	-1.7	246	246
CPT1C	-0.53	0.54	-9999	-1.1	189	189
ALAS1	-0.16	0.21	-9999	-10000	0	0
TFRC	-0.26	0.3	-9999	-0.86	25	25
FOXF1	-0.011	0.092	-9999	-0.75	7	7
NF1	0.021	0.001	-9999	-10000	0	0
HNF1A (dimer)	0.015	0.007	-9999	-10000	0	0
CPT1A	-0.51	0.54	-9999	-1.1	185	185
HMGCS1	-0.51	0.54	-9999	-1.1	183	183
NR3C1	0.019	0.017	-9999	-10000	0	0
CPT1B	-0.51	0.54	-9999	-1.1	184	184
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.66	0.7	-9999	-1.4	211	211
CREB1	0.001	0.052	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.6	4	4
PDX1	-0.18	0.21	-9999	-10000	0	0
UCP2	-0.51	0.54	-9999	-1.1	187	187
ALDOB	-0.48	0.54	-9999	-1.1	173	173
AFP	-0.049	0.11	-9999	-0.51	7	7
BDH1	-0.51	0.54	-9999	-1.1	192	192
HADH	-0.48	0.54	-9999	-1.1	181	181
F2	-0.62	0.63	-9999	-1.3	202	202
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.006	0.091	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.82	1	1
INS	-0.008	0.019	-9999	-10000	0	0
FOXA1	-0.061	0.15	-9999	-0.36	65	65
FOXA3	-0.074	0.17	-9999	-0.5	35	35
FOXA2	-0.55	0.61	-9999	-1.2	200	200
ABCC8	-0.78	0.75	-9999	-1.4	258	258
ALB	-0.1	0.32	-9999	-1.3	31	31

×

Nongenotropic Androgen signaling

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
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.21	0.25	-10000	0	-0.5	206	206
regulation of S phase of mitotic cell cycle	-0.12	0.18	-10000	0	-0.34	207	207
GNAO1	-0.017	0.15	-10000	0	-0.82	16	16
HRAS	0.011	0.021	-10000	0	-0.32	2	2
SHBG/T-DHT	-0.008	0.071	-10000	0	-0.56	8	8
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0.001	-10000	0	-10000	0	0
MAP2K1	-0.16	0.23	-10000	0	-0.43	205	205
T-DHT/AR	-0.27	0.32	-10000	0	-0.64	205	205
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	128	128
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
mol:GDP	-0.26	0.3	-10000	0	-0.61	207	207
cell proliferation	-0.2	0.28	-10000	0	-0.54	138	138
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
FOS	-0.24	0.4	-10000	0	-0.89	128	128
mol:Ca2+	-0.027	0.03	-10000	0	-0.071	93	93
MAPK3	-0.18	0.26	-10000	0	-0.45	207	207
MAPK1	-0.083	0.13	-10000	0	-0.3	78	78
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	128	128
cAMP biosynthetic process	0.016	0.075	-10000	0	-0.52	8	8
GNG2	0.012	0.038	-10000	0	-0.82	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	128	128
HRAS/GTP	-0.2	0.23	-10000	0	-0.47	205	205
actin cytoskeleton reorganization	-0.003	0.034	-10000	0	-0.44	3	3
SRC	0.012	0.015	-10000	0	-0.32	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	128	128
PI3K	-0.003	0.043	-10000	0	-0.55	3	3
apoptosis	0.16	0.25	0.52	129	-10000	0	129
T-DHT/AR/PELP1	-0.23	0.27	-10000	0	-0.55	205	205
HRAS/GDP	-0.24	0.29	-10000	0	-0.58	206	206
CREB1	-0.18	0.27	-10000	0	-0.57	129	129
RAC1-CDC42/GTP	-0.003	0.035	-10000	0	-0.45	3	3
AR	-0.34	0.41	-10000	0	-0.82	205	205
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.17	0.24	-10000	0	-0.45	205	205
RAC1-CDC42/GDP	-0.23	0.27	-10000	0	-0.55	205	205
T-DHT/AR/PELP1/Src	-0.21	0.25	-10000	0	-0.51	205	205
MAP2K2	-0.16	0.23	-10000	0	-0.43	205	205
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.18	-10000	0	-0.34	207	207
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	0	0.1	-10000	0	-0.82	8	8
Gi family/GNB1/GNG2/GDP	-0.02	0.12	-10000	0	-0.54	16	16
mol:T-DHT	0	0.001	0.002	76	-0.003	50	126
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.043	-10000	0	-0.5	3	3
Gi family/GTP	-0.095	0.12	-10000	0	-0.47	18	18
CDC42	0.013	0	-10000	0	-10000	0	0

×

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	-0.11	0.26	-10000	0	-0.68	35	35
IHH	-0.2	0.37	-10000	0	-0.84	121	121
SHH Np/Cholesterol/GAS1	-0.1	0.2	-10000	0	-0.51	97	97
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.1	0.2	0.51	97	-10000	0	97
SMO/beta Arrestin2	-0.095	0.24	-10000	0	-0.68	16	16
SMO	-0.11	0.25	-10000	0	-0.51	124	124
AKT1	-0.027	0.12	-10000	0	-0.66	2	2
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	0	0.1	-10000	0	-0.82	8	8
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.1	0.25	-10000	0	-0.5	124	124
STIL	-0.077	0.2	-10000	0	-0.59	18	18
DHH N/PTCH2	-0.11	0.24	-10000	0	-0.64	82	82
DHH N/PTCH1	-0.099	0.22	-10000	0	-0.45	128	128
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
DHH	0.006	0.075	-10000	0	-0.82	4	4
PTHLH	-0.16	0.37	-10000	0	-1.2	35	35
determination of left/right symmetry	-0.1	0.25	-10000	0	-0.5	124	124
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.15	0.36	-10000	0	-1.1	35	35
IHH N/Hhip	-0.38	0.4	-10000	0	-0.73	258	258
DHH N/Hhip	-0.25	0.31	-10000	0	-0.63	191	191
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.1	0.25	-10000	0	-0.5	124	124
pancreas development	-0.31	0.4	-10000	0	-0.81	191	191
HHAT	0.012	0.038	-10000	0	-0.82	1	1
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.15	0.33	-10000	0	-0.82	96	96
somite specification	-0.1	0.25	-10000	0	-0.5	124	124
SHH Np/Cholesterol/PTCH1	-0.087	0.2	-10000	0	-0.62	17	17
SHH Np/Cholesterol/PTCH2	-0.088	0.19	-10000	0	-0.51	81	81
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.51	132	132
SHH	0.007	0.049	-10000	0	-0.63	1	1
catabolic process	-0.11	0.25	-10000	0	-0.51	124	124
SMO/Vitamin D3	-0.091	0.22	-10000	0	-0.65	17	17
SHH Np/Cholesterol/Hhip	-0.2	0.24	-10000	0	-0.51	190	190
LRP2	-0.21	0.37	-10000	0	-0.82	131	131
receptor-mediated endocytosis	-0.2	0.23	-10000	0	-0.72	47	47
SHH Np/Cholesterol/BOC	-0.014	0.074	-10000	0	-0.52	9	9
SHH Np/Cholesterol/CDO	-0.15	0.23	-10000	0	-0.51	144	144
mesenchymal cell differentiation	0.2	0.24	0.5	190	-10000	0	190
mol:Vitamin D3	-0.086	0.21	-10000	0	-0.62	17	17
IHH N/PTCH2	-0.23	0.34	-10000	0	-0.66	180	180
CDON	-0.23	0.38	-10000	0	-0.82	143	143
IHH N/PTCH1	-0.12	0.25	-10000	0	-0.51	124	124
Megalin/LRPAP1	-0.17	0.28	-10000	0	-0.63	131	131
PTCH2	-0.12	0.31	-10000	0	-0.82	80	80
SHH Np/Cholesterol	-0.006	0.035	-10000	0	-0.51	1	1
PTCH1	-0.11	0.25	-10000	0	-0.51	124	124
HHIP	-0.31	0.4	-10000	0	-0.81	191	191

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.08	-9999	-0.56	9	9
NFATC2	-0.1	0.22	-9999	-0.57	85	85
NFATC3	0	0.027	-9999	-10000	0	0
CD40LG	-0.43	0.41	-9999	-0.88	192	192
PTGS2	-0.41	0.4	-9999	-0.86	178	178
JUNB	0.003	0.091	-9999	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.015	-9999	-10000	0	0
CALM1	0.008	0.008	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.82	110	110
mol:Ca2+	-0.01	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.004	-9999	-10000	0	0
FOSL1	-0.03	0.12	-9999	-0.33	62	62
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.59	167	167
FOS	-0.21	0.36	-9999	-0.82	128	128
IFNG	-0.43	0.4	-9999	-0.86	196	196
AP-1/NFAT1-c-4	-0.52	0.5	-9999	-1.1	183	183
FASLG	-0.41	0.39	-9999	-0.83	185	185
NFAT1-c-4/ICER1	-0.11	0.2	-9999	-0.5	93	93
IL2RA	-0.4	0.38	-9999	-0.83	179	179
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.47	0.36	-9999	-0.79	237	237
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.5	94	94
IL4	-0.39	0.36	-9999	-0.8	177	177
IL2	-0.012	0.026	-9999	-10000	0	0
IL3	-0.032	0.03	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.006	0.082	-9999	-0.33	27	27
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.015	-9999	-0.31	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.17	0.3	0.69	118	-10000	0	118
KIRREL	-0.071	0.24	-10000	0	-0.84	42	42
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.17	0.3	-10000	0	-0.69	118	118
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.13	0.24	-10000	0	-0.54	118	118
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.076	0.2	-10000	0	-0.41	118	118
FYN	-0.11	0.24	-10000	0	-0.51	118	118
mol:Ca2+	-0.13	0.24	-10000	0	-0.53	118	118
mol:DAG	-0.13	0.24	-10000	0	-0.53	118	118
NPHS2	-0.017	0.052	-10000	0	-0.89	1	1
mol:IP3	-0.13	0.24	-10000	0	-0.53	118	118
regulation of endocytosis	-0.12	0.21	-10000	0	-0.48	118	118
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.55	118	118
establishment of cell polarity	-0.17	0.3	-10000	0	-0.69	118	118
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.22	-10000	0	-0.49	118	118
Nephrin/NEPH1/beta Arrestin2	-0.1	0.23	-10000	0	-0.48	118	118
NPHS1	-0.15	0.32	-10000	0	-0.82	90	90
Nephrin/NEPH1/podocin	-0.12	0.23	-10000	0	-0.51	118	118
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.13	0.24	-10000	0	-0.54	118	118
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.13	0.24	-10000	0	-0.54	118	118
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.11	0.25	-10000	0	-0.51	122	122
cytoskeleton organization	-0.1	0.26	-10000	0	-0.53	118	118
Nephrin/NEPH1	-0.13	0.24	-10000	0	-0.53	118	118
Nephrin/NEPH1/ZO-1	-0.14	0.26	-10000	0	-0.57	118	118

×

Lissencephaly gene (LIS1) in neuronal migration and development

Figure S16. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S16. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	-0.022	0.17	-9999	-0.82	21	21
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.42	0.26	-9999	-0.56	361	361
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.37	0.25	-9999	-0.51	361	361
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.095	0.28	-9999	-0.82	64	64
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.026	0.12	-9999	-0.63	20	20
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.012	0.021	-9999	-0.31	2	2
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	0.004	0.021	-9999	-0.31	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.42	0.26	-9999	-0.56	363	363
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.27	0.2	-9999	-0.72	16	16
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.32	0.23	-9999	-0.44	361	361
RELN	-0.6	0.37	-9999	-0.82	357	357
PAFAH/LIS1	-0.047	0.19	-9999	-0.54	64	64
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.22	0.14	-9999	-0.54	16	16
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.25	0.18	-9999	-0.34	364	364
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.3	0.22	-9999	-0.79	16	16
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.024	0	-9999	-10000	0	0
PAFAH1B3	0.011	0.029	-9999	-10000	0	0
PAFAH1B2	-0.002	0.11	-9999	-0.82	9	9
MAP1B/LIS1/Dynein heavy chain	0.027	0.003	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.27	0.17	-9999	-0.69	16	16
LRP8	-0.021	0.16	-9999	-0.82	20	20
NDEL1/Katanin 60	-0.27	0.2	-9999	-0.72	16	16
P39/CDK5	-0.32	0.23	-9999	-0.45	361	361
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.34	0.24	-9999	-0.47	361	361
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.36	0.22	-9999	-0.48	363	363
RELN/VLDLR	-0.4	0.26	-9999	-0.53	367	367
CDC42	0	0	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.001	0.025	-10000	0	-0.54	1	1
fibroblast growth factor receptor signaling pathway	-0.001	0.025	-10000	0	-0.54	1	1
LAMA1	-0.049	0.22	-10000	0	-0.8	37	37
PRNP	0.012	0.038	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.095	0.22	-10000	0	-0.63	73	73
SMAD2	0.028	0.048	-10000	0	-0.49	3	3
GPC1/PrPc/Cu2+	-0.001	0.026	-10000	0	-0.55	1	1
GPC1/Laminin alpha1	-0.047	0.16	-10000	0	-0.63	36	36
TDGF1	-0.34	0.41	-10000	0	-0.82	207	207
CRIPTO/GPC1	-0.27	0.31	-10000	0	-0.63	207	207
APP/GPC1	0	0.009	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.21	0.28	-10000	0	-0.54	207	207
FLT1	0.012	0.038	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.007	0.048	-10000	0	-0.54	3	3
SERPINC1	0.006	0.044	-10000	0	-0.31	9	9
FYN	-0.21	0.28	-10000	0	-0.54	207	207
FGR	-0.21	0.28	-10000	0	-0.54	207	207
positive regulation of MAPKKK cascade	-0.28	0.31	-10000	0	-0.61	209	209
SLIT2	-0.11	0.3	-10000	0	-0.8	76	76
GPC1/NRG	-0.059	0.18	-10000	0	-0.63	45	45
NRG1	-0.064	0.24	-10000	0	-0.8	47	47
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.005	0.058	-10000	0	-0.7	3	3
LYN	-0.21	0.28	-10000	0	-0.54	207	207
mol:Spermine	0.012	0.01	-10000	0	-10000	0	0
cell growth	-0.001	0.025	-10000	0	-0.54	1	1
BMP signaling pathway	-0.013	0.015	0.31	1	-10000	0	1
SRC	-0.21	0.28	-10000	0	-0.54	207	207
TGFBR1	0.006	0.048	-10000	0	-0.31	11	11
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.25	0.36	-10000	0	-0.68	184	184
GPC1	0.013	0.015	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.006	0.048	-10000	0	-0.31	11	11
VEGFA	0.008	0.065	-10000	0	-0.82	3	3
BLK	-0.38	0.37	-10000	0	-0.66	281	281
HCK	-0.22	0.28	-10000	0	-0.55	207	207
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.012	0.038	-10000	0	-0.82	1	1
VEGFR1 homodimer	0.012	0.037	-10000	0	-0.82	1	1
TGFBR2	0.008	0.065	-10000	0	-0.82	3	3
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.004	0.029	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.19	0.27	-10000	0	-0.63	134	134
LCK	-0.23	0.28	-10000	0	-0.55	212	212
neuron differentiation	-0.059	0.18	-10000	0	-0.62	45	45
PrPc/Cu2+	-0.001	0.029	-10000	0	-0.64	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.008	0.065	-10000	0	-0.82	3	3

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.065	-10000	0	-0.82	3	3
EFNB1	0	0.12	-10000	0	-0.63	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.25	0.24	-10000	0	-0.52	205	205
Ephrin B2/EPHB1-2	-0.2	0.24	-10000	0	-0.5	192	192
neuron projection morphogenesis	-0.24	0.23	-10000	0	-0.5	205	205
Ephrin B1/EPHB1-2/Tiam1	-0.27	0.26	-10000	0	-0.56	205	205
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.005	0.089	-10000	0	-0.78	6	6
YES1	-0.01	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/NCK2	-0.19	0.24	-10000	0	-0.47	205	205
PI3K	0.003	0.12	-10000	0	-1	6	6
mol:GDP	-0.26	0.26	-10000	0	-0.55	205	205
ITGA2B	-0.072	0.25	-10000	0	-0.82	50	50
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.01	0.11	-10000	0	-1	6	6
MAP3K7	-0.012	0.092	-10000	0	-0.83	6	6
FGR	-0.012	0.11	-10000	0	-1	6	6
TIAM1	-0.17	0.16	-10000	0	-0.32	277	277
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.041	0.2	-10000	0	-0.53	63	63
LYN	-0.01	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.014	0.1	-10000	0	-0.96	6	6
Ephrin B1/EPHB1-2	-0.02	0.098	-10000	0	-0.89	6	6
SRC	-0.012	0.11	-10000	0	-1	6	6
ITGB3	-0.01	0.14	-10000	0	-0.82	14	14
EPHB1	-0.31	0.4	-10000	0	-0.82	190	190
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.081	0.22	-10000	0	-0.67	59	59
BLK	-0.066	0.14	-10000	0	-1.1	6	6
HCK	-0.013	0.11	-10000	0	-1	6	6
regulation of stress fiber formation	0.19	0.24	0.46	205	-10000	0	205
MAPK8	0.003	0.13	-10000	0	-0.78	12	12
Ephrin B1/EPHB1-2/RGS3	-0.19	0.24	-10000	0	-0.47	205	205
endothelial cell migration	-0.006	0.081	-10000	0	-0.72	6	6
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.004	0.1	-10000	0	-0.93	6	6
regulation of focal adhesion formation	0.19	0.24	0.46	205	-10000	0	205
chemotaxis	0.19	0.24	0.46	205	-10000	0	205
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
Rac1/GTP	-0.24	0.24	-10000	0	-0.51	205	205
angiogenesis	-0.02	0.098	-10000	0	-0.89	6	6
LCK	-0.015	0.12	-10000	0	-1	6	6

×

Endothelins

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
AKT1	-0.051	0.14	-9999	-0.51	12	12
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.7	60	60
EDN1	-0.042	0.12	-9999	-0.79	6	6
EDN3	-0.39	0.41	-9999	-0.81	240	240
EDN2	-0.014	0.12	-9999	-0.41	32	32
HRAS/GDP	-0.1	0.24	-9999	-0.54	81	81
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.084	0.18	-9999	-0.39	90	90
ADCY4	-0.095	0.19	-9999	-0.5	70	70
ADCY5	-0.16	0.25	-9999	-0.55	117	117
ADCY6	-0.095	0.19	-9999	-0.5	69	69
ADCY7	-0.095	0.19	-9999	-0.5	69	69
ADCY1	-0.1	0.21	-9999	-0.52	72	72
ADCY2	-0.14	0.24	-9999	-0.55	103	103
ADCY3	-0.095	0.19	-9999	-0.5	69	69
ADCY8	-0.2	0.2	-9999	-0.54	96	96
ADCY9	-0.095	0.19	-9999	-0.5	69	69
arachidonic acid secretion	-0.17	0.32	-9999	-0.65	132	132
ETB receptor/Endothelin-1/Gq/GTP	-0.096	0.22	-9999	-0.43	117	117
GNAO1	-0.017	0.15	-9999	-0.82	16	16
HRAS	0.01	0.021	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.16	-9999	-0.49	11	11
ETA receptor/Endothelin-1/Gs/GTP	-0.08	0.22	-9999	-0.52	71	71
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.068	0.17	-9999	-0.5	39	39
EDNRB	0.003	0.093	-9999	-0.83	6	6
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.15	0.24	-9999	-0.63	55	55
CYSLTR1	-0.062	0.18	-9999	-0.75	17	17
SLC9A1	-0.021	0.076	-9999	-0.3	6	6
mol:GDP	-0.12	0.26	-9999	-0.55	94	94
SLC9A3	-0.048	0.19	-9999	-0.8	21	21
RAF1	-0.15	0.3	-9999	-0.57	135	135
JUN	-0.28	0.51	-9999	-1.2	119	119
JAK2	-0.053	0.15	-9999	-0.54	13	13
mol:IP3	-0.11	0.23	-9999	-0.5	101	101
ETA receptor/Endothelin-1	-0.034	0.2	-9999	-0.47	38	38
PLCB1	0.009	0.038	-9999	-0.82	1	1
PLCB2	0.005	0.043	-9999	-0.32	8	8
ETA receptor/Endothelin-3	-0.32	0.33	-9999	-0.66	240	240
FOS	-0.26	0.48	-9999	-1	130	130
Gai/GDP	-0.003	0.13	-9999	-0.66	16	16
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.12	0.23	-9999	-0.57	63	63
BCAR1	0.013	0.002	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.48	102	102
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.09	0.27	-9999	-0.82	61	61
Gs family/GDP	-0.18	0.25	-9999	-0.56	119	119
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.46	102	102
MAPK14	-0.063	0.18	-9999	-0.48	34	34
TRPC6	-0.14	0.3	-9999	-0.76	59	59
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.82	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.075	0.18	-9999	-0.4	83	83
ETB receptor/Endothelin-2	-0.026	0.11	-9999	-0.63	12	12
ETB receptor/Endothelin-3	-0.31	0.32	-9999	-0.63	242	242
ETB receptor/Endothelin-1	-0.019	0.12	-9999	-0.63	12	12
MAPK3	-0.23	0.43	-9999	-0.89	136	136
MAPK1	-0.23	0.43	-9999	-0.89	136	136
Rac1/GDP	-0.1	0.24	-9999	-0.53	79	79
cAMP biosynthetic process	-0.14	0.21	-9999	-0.54	79	79
MAPK8	-0.17	0.35	-9999	-0.72	99	99
SRC	0.012	0.015	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.009	0.078	-9999	-0.36	7	7
p130Cas/CRK/Src/PYK2	-0.13	0.29	-9999	-0.61	98	98
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.53	79	79
COL1A2	-0.037	0.16	-9999	-0.6	10	10
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.57	10	10
mol:DAG	-0.11	0.23	-9999	-0.5	101	101
MAP2K2	-0.18	0.35	-9999	-0.69	139	139
MAP2K1	-0.18	0.35	-9999	-0.69	139	139
EDNRA	-0.038	0.1	-9999	-0.54	5	5
positive regulation of muscle contraction	-0.036	0.12	-9999	-0.48	9	9
Gq family/GDP	-0.19	0.29	-9999	-0.67	112	112
HRAS/GTP	-0.13	0.26	-9999	-0.57	94	94
PRKCH	-0.1	0.22	-9999	-0.52	79	79
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.26	-9999	-0.54	106	106
PRKCB	-0.12	0.23	-9999	-0.52	92	92
PRKCE	-0.1	0.24	-9999	-0.53	85	85
PRKCD	-0.1	0.22	-9999	-0.51	83	83
PRKCG	-0.11	0.22	-9999	-0.51	89	89
regulation of vascular smooth muscle contraction	-0.3	0.55	-9999	-1.2	130	130
PRKCQ	-0.11	0.23	-9999	-0.51	92	92
PLA2G4A	-0.19	0.36	-9999	-0.72	132	132
GNA14	-0.18	0.35	-9999	-0.82	114	114
GNA15	-0.016	0.094	-9999	-0.33	39	39
GNA12	0.013	0	-9999	-10000	0	0
GNA11	-0.006	0.12	-9999	-0.82	10	10
Rac1/GTP	-0.013	0.16	-9999	-0.49	11	11
MMP1	-0.096	0.16	-9999	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	-0.18	0.42	-9999	-0.91	64	64
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.34	-9999	-0.82	106	106
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.18	0.42	-9999	-0.92	64	64
AP1	-0.28	0.45	-9999	-0.92	151	151
ABCG2	-0.19	0.42	-9999	-0.96	56	56
HIF1A	-0.008	0.067	-9999	-10000	0	0
TFF3	-0.56	0.51	-9999	-1	198	198
GATA2	0.014	0.015	-9999	-0.31	1	1
AKT1	-0.038	0.1	-9999	-10000	0	0
response to hypoxia	-0.059	0.11	-9999	-0.24	41	41
MCL1	-0.18	0.42	-9999	-0.94	56	56
NDRG1	-0.18	0.42	-9999	-0.91	64	64
SERPINE1	-0.19	0.42	-9999	-0.93	66	66
FECH	-0.18	0.42	-9999	-0.92	61	61
FURIN	-0.18	0.42	-9999	-0.91	65	65
NCOA2	-0.066	0.24	-9999	-0.82	47	47
EP300	-0.062	0.18	-9999	-0.33	108	108
HMOX1	-0.19	0.42	-9999	-0.92	65	65
BHLHE40	-0.19	0.42	-9999	-0.95	60	60
BHLHE41	-0.18	0.42	-9999	-0.92	66	66
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.016	0.036	-9999	-10000	0	0
ENG	0.042	0.092	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.82	110	110
RORA	-0.18	0.42	-9999	-0.93	64	64
ABCB1	-0.075	0.18	-9999	-1.4	8	8
TFRC	-0.18	0.42	-9999	-0.95	58	58
CXCR4	-0.18	0.42	-9999	-0.9	68	68
TF	-0.23	0.48	-9999	-1	90	90
CITED2	-0.21	0.47	-9999	-1	79	79
HIF1A/ARNT	-0.29	0.38	-9999	-1	68	68
LDHA	-0.038	0.05	-9999	-10000	0	0
ETS1	-0.18	0.42	-9999	-0.92	60	60
PGK1	-0.18	0.42	-9999	-0.9	68	68
NOS2	-0.2	0.43	-9999	-0.91	75	75
ITGB2	-0.19	0.42	-9999	-0.93	64	64
ALDOA	-0.18	0.42	-9999	-0.92	61	61
Cbp/p300/CITED2	-0.32	0.5	-9999	-1.1	106	106
FOS	-0.2	0.36	-9999	-0.82	128	128
HK2	-0.18	0.42	-9999	-0.91	66	66
SP1	0.022	0.01	-9999	-10000	0	0
GCK	-0.39	0.71	-9999	-1.5	136	136
HK1	-0.18	0.42	-9999	-0.93	58	58
NPM1	-0.18	0.42	-9999	-0.9	68	68
EGLN1	-0.18	0.42	-9999	-0.92	66	66
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.18	0.42	-9999	-0.91	65	65
SMAD3	0.015	0.003	-9999	-10000	0	0
EDN1	-0.16	0.31	-9999	-0.73	65	65
IGFBP1	-0.2	0.42	-9999	-0.93	64	64
VEGFA	-0.15	0.38	-9999	-0.76	74	74
HIF1A/JAB1	-0.011	0.02	-9999	-10000	0	0
CP	-0.34	0.55	-9999	-1	147	147
CXCL12	-0.23	0.48	-9999	-1	81	81
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.18	0.42	-9999	-0.9	68	68
EGLN3	-0.2	0.43	-9999	-0.94	70	70
CA9	-0.2	0.42	-9999	-0.92	69	69
TERT	-0.19	0.41	-9999	-0.91	68	68
ENO1	-0.18	0.42	-9999	-0.9	68	68
PFKL	-0.18	0.42	-9999	-0.93	58	58
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.22	0.44	-9999	-0.92	78	78
ARNT	-0.009	0.067	-9999	-10000	0	0
HNF4A	-0.026	0.065	-9999	-0.35	10	10
ADFP	-0.2	0.41	-9999	-0.91	68	68
SLC2A1	-0.15	0.38	-9999	-0.75	73	73
LEP	-0.2	0.42	-9999	-0.92	65	65
HIF1A/ARNT/Cbp/p300	-0.29	0.36	-9999	-0.86	105	105
EPO	-0.14	0.33	-9999	-0.95	27	27
CREBBP	-0.062	0.18	-9999	-0.34	107	107
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.82	105	105
PFKFB3	-0.18	0.42	-9999	-0.9	69	69
NT5E	-0.19	0.42	-9999	-0.96	58	58

×

IGF1 pathway

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
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.13	0.24	-10000	0	-0.45	159	159
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.021	-10000	0	-0.31	2	2
IRS1/Crk	-0.13	0.24	-10000	0	-0.45	159	159
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.22	-10000	0	-0.52	113	113
AKT1	-0.092	0.22	-10000	0	-0.77	16	16
BAD	-0.078	0.2	-10000	0	-0.7	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.13	0.24	-10000	0	-0.45	159	159
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.24	-10000	0	-0.46	159	159
RAF1	-0.068	0.19	-10000	0	-0.65	16	16
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.21	-10000	0	-0.42	159	159
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.16	0.24	-10000	0	-0.49	159	159
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
RPS6KB1	-0.092	0.22	-10000	0	-0.77	16	16
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.06	0.16	-10000	0	-0.53	16	16
PXN	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.19	-10000	0	-0.41	114	114
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.18	-10000	0	-0.42	113	113
IGF-1R heterotetramer	-0.019	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.15	0.22	-10000	0	-0.45	159	159
Crk/p130 Cas/Paxillin	-0.13	0.2	-10000	0	-0.79	13	13
IGF1R	-0.019	0.048	-10000	0	-10000	0	0
IGF1	-0.2	0.36	-10000	0	-0.84	113	113
IRS2/Crk	-0.12	0.23	-10000	0	-0.46	113	113
PI3K	-0.14	0.22	-10000	0	-0.43	159	159
apoptosis	0.06	0.18	0.57	16	-10000	0	16
HRAS/GDP	-0.001	0.014	-10000	0	-10000	0	0
PRKCD	-0.11	0.24	-10000	0	-0.53	113	113
RAF1/14-3-3 E	-0.051	0.17	-10000	0	-0.53	16	16
BAD/14-3-3	-0.064	0.19	-10000	0	-0.62	16	16
PRKCZ	-0.092	0.22	-10000	0	-0.77	16	16
Crk/p130 Cas/Paxillin/FAK1	-0.1	0.16	-10000	0	-0.63	16	16
PTPN1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.12	0.25	-10000	0	-0.56	113	113
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.19	-10000	0	-0.46	113	113
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.13	0.24	-10000	0	-0.45	159	159
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.13	0.24	-10000	0	-0.45	159	159
IRS1	-0.15	0.25	-10000	0	-0.49	159	159
IRS2	-0.13	0.24	-10000	0	-0.45	159	159
IGF-1R heterotetramer/IGF1	-0.16	0.27	-10000	0	-0.66	113	113
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.11	0.23	-10000	0	-0.45	114	114
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.24	-10000	0	-0.53	114	114
SHC1	0.013	0	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	0.045	0.094	-10000	0	-10000	0	0
SMARCC2	0.014	0.014	-10000	0	-10000	0	0
SMARCC1	0.013	0.014	-10000	0	-10000	0	0
TBX21	-0.15	0.28	-10000	0	-0.65	77	77
SUMO2	0.014	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.05	-10000	0	-0.31	11	11
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.003	0.091	-10000	0	-0.82	6	6
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.33	52	-0.49	6	58
PRL	-0.088	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.25	0.31	0.58	156	-0.48	24	180
RELA	-0.036	0.088	-10000	0	-10000	0	0
FGG	0.24	0.19	0.52	106	-10000	0	106
GR beta/TIF2	0.081	0.24	0.34	77	-0.55	47	124
IFNG	-0.5	0.51	-10000	0	-1.1	150	150
apoptosis	0.035	0.24	0.52	53	-0.56	2	55
CREB1	0.011	0.023	-10000	0	-10000	0	0
histone acetylation	-0.07	0.16	-10000	0	-0.42	54	54
BGLAP	-0.099	0.15	-10000	0	-0.55	8	8
GR/PKAc	0.13	0.1	0.34	32	-0.41	1	33
NF kappa B1 p50/RelA	-0.074	0.16	-10000	0	-0.47	27	27
SMARCD1	0.013	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.094	0.27	103	-10000	0	103
GATA3	-0.027	0.18	-10000	0	-0.78	27	27
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.58	33	33
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.062	0.23	0.51	42	-0.74	5	47
CSN2	0.2	0.14	0.42	81	-10000	0	81
BRG1/BAF155/BAF170/BAF60A	0.018	0.049	-10000	0	-10000	0	0
NFATC1	0	0.11	-10000	0	-0.82	9	9
POU2F1	0.013	0.015	-10000	0	-0.3	1	1
CDKN1A	0.023	0.055	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.012	-10000	0	-10000	0	0
SFN	-0.21	0.18	-10000	0	-0.33	314	314
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.047	0.16	0.35	14	-0.48	13	27
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.075	0.44	0.5	37	-0.88	104	141
JUN	-0.33	0.3	-10000	0	-0.72	156	156
IL4	-0.13	0.18	-10000	0	-0.62	28	28
CDK5R1	0.012	0.022	-10000	0	-0.32	2	2
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.37	0.41	-10000	0	-0.83	181	181
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.34	35	-0.47	5	40
cortisol/GR alpha (monomer)	0.37	0.3	0.69	179	-10000	0	179
NCOA2	-0.067	0.24	-10000	0	-0.82	47	47
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.25	0.36	-10000	0	-0.84	128	128
AP-1/NFAT1-c-4	-0.56	0.48	-10000	0	-0.99	221	221
AFP	-0.22	0.22	-10000	0	-0.71	30	30
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.14	0.48	53	-10000	0	53
TP53	0.032	0.025	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.48	0.37	-10000	0	-0.9	143	143
KRT14	-0.24	0.18	-10000	0	-0.63	17	17
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.064	0.066	-10000	0	-10000	0	0
HDAC1	0.011	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.013	-10000	0	-10000	0	0
AP-1	-0.56	0.48	-10000	0	-1	222	222
MAPK14	0.014	0.011	-10000	0	-10000	0	0
MAPK10	0.013	0.04	-10000	0	-0.82	1	1
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.54	0.52	-10000	0	-1.1	170	170
interleukin-1 receptor activity	0.017	0.013	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	0.015	0.05	-10000	0	-0.31	11	11
CGA	-0.12	0.16	-10000	0	-0.55	20	20
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.38	180	-10000	0	180
MAPK3	0.014	0.012	-10000	0	-10000	0	0
MAPK1	0.014	0.011	-10000	0	-10000	0	0
ICAM1	-0.26	0.26	-10000	0	-0.7	85	85
NFKB1	-0.038	0.097	-10000	0	-0.94	1	1
MAPK8	-0.19	0.21	-10000	0	-0.53	92	92
MAPK9	0.014	0.011	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.029	0.24	0.53	50	-0.58	2	52
BAX	0.028	0.035	-10000	0	-10000	0	0
POMC	-0.54	0.69	-10000	0	-1.6	120	120
EP300	0.065	0.067	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.33	0.24	0.6	166	-10000	0	166
proteasomal ubiquitin-dependent protein catabolic process	0.087	0.071	0.24	35	-10000	0	35
SGK1	0.1	0.24	-10000	0	-1.4	11	11
IL13	-0.3	0.25	-10000	0	-0.81	57	57
IL6	-0.4	0.53	-10000	0	-1.2	129	129
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.71	45	45
IL2	-0.36	0.27	-10000	0	-0.8	84	84
CDK5	0.013	0.007	-10000	0	-10000	0	0
PRKACB	0.012	0.038	-10000	0	-0.82	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.27	0.32	-10000	0	-0.75	95	95
CDK5R1/CDK5	0.007	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.032	0.12	-10000	0	-0.63	2	2
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	162	-10000	0	162
SMARCA4	0.014	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.41	107	-0.39	1	108
NF kappa B1 p50/RelA/Cbp	0.018	0.16	-10000	0	-0.52	5	5
JUN (dimer)	-0.33	0.3	-10000	0	-0.72	156	156
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.41	-10000	0	-1	92	92
NR3C1	0.22	0.19	0.48	124	-10000	0	124
NR4A1	-0.31	0.41	-10000	0	-0.75	205	205
TIF2/SUV420H1	-0.06	0.18	-10000	0	-0.63	47	47
MAPKKK cascade	0.035	0.24	0.52	53	-0.56	2	55
cortisol/GR alpha (dimer)/Src-1	0.32	0.23	0.59	169	-10000	0	169
PBX1	0.012	0.038	-10000	0	-0.82	1	1
POU1F1	0.007	0.008	-10000	0	-10000	0	0
SELE	-0.35	0.5	-10000	0	-1.2	101	101
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.41	107	-0.4	1	108
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	162	-10000	0	162
mol:cortisol	0.21	0.19	0.4	189	-10000	0	189
MMP1	-0.22	0.15	-10000	0	-0.44	57	57

×

IL23-mediated signaling events

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
CCL2	-0.22	0.55	-10000	0	-1.3	77	77
IL23A	-0.23	0.56	-10000	0	-1.3	88	88
NF kappa B1 p50/RelA/I kappa B alpha	-0.3	0.47	-10000	0	-1.2	87	87
positive regulation of T cell mediated cytotoxicity	-0.25	0.62	-10000	0	-1.4	87	87
ITGA3	-0.2	0.52	-10000	0	-1.2	79	79
IL17F	-0.11	0.34	-10000	0	-0.75	72	72
IL12B	-0.001	0.1	-10000	0	-0.56	11	11
STAT1 (dimer)	-0.24	0.58	-10000	0	-1.3	89	89
CD4	-0.2	0.51	-10000	0	-1.2	81	81
IL23	-0.24	0.54	-10000	0	-1.2	87	87
IL23R	-0.005	0.099	-10000	0	-10000	0	0
IL1B	-0.24	0.59	-10000	0	-1.3	87	87
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.2	0.51	-10000	0	-1.1	84	84
TYK2	0.014	0.023	-10000	0	-10000	0	0
STAT4	-0.024	0.14	-10000	0	-0.46	39	39
STAT3	0.013	0	-10000	0	-10000	0	0
IL18RAP	-0.023	0.16	-10000	0	-0.79	21	21
IL12RB1	-0.022	0.12	-10000	0	-0.43	24	24
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
IL12Rbeta1/TYK2	-0.009	0.093	-10000	0	-0.67	4	4
IL23R/JAK2	-0.003	0.13	-10000	0	-0.63	2	2
positive regulation of chronic inflammatory response	-0.25	0.62	-10000	0	-1.4	87	87
natural killer cell activation	0.001	0.009	0.036	1	-10000	0	1
JAK2	0.019	0.061	-10000	0	-0.84	2	2
PIK3R1	0.013	0	-10000	0	-10000	0	0
NFKB1	0.011	0.038	-10000	0	-0.82	1	1
RELA	0.013	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.22	0.5	-10000	0	-1.1	87	87
ALOX12B	-0.22	0.52	-10000	0	-1.2	86	86
CXCL1	-0.22	0.53	-10000	0	-1.2	83	83
T cell proliferation	-0.25	0.62	-10000	0	-1.4	87	87
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.062	0.28	-10000	0	-0.59	57	57
PI3K	-0.31	0.49	-10000	0	-1.2	87	87
IFNG	-0.02	0.054	-10000	0	-0.14	67	67
STAT3 (dimer)	-0.29	0.45	-10000	0	-1.2	85	85
IL18R1	-0.03	0.14	-10000	0	-0.43	47	47
IL23/IL23R/JAK2/TYK2/SOCS3	-0.1	0.33	-10000	0	-0.77	51	51
IL18/IL18R	-0.065	0.18	-10000	0	-0.56	45	45
macrophage activation	-0.015	0.018	-10000	0	-0.044	87	87
TNF	-0.27	0.63	-10000	0	-1.4	101	101
STAT3/STAT4	-0.31	0.5	-10000	0	-1.3	90	90
STAT4 (dimer)	-0.25	0.59	-10000	0	-1.3	90	90
IL18	-0.039	0.15	-10000	0	-0.41	58	58
IL19	-0.2	0.51	-10000	0	-1.2	70	70
STAT5A (dimer)	-0.24	0.58	-10000	0	-1.3	87	87
STAT1	0.006	0.048	-10000	0	-0.31	11	11
SOCS3	-0.033	0.19	-10000	0	-0.8	28	28
CXCL9	-0.3	0.63	-10000	0	-1.4	108	108
MPO	-0.2	0.51	-10000	0	-1.2	79	79
positive regulation of humoral immune response	-0.25	0.62	-10000	0	-1.4	87	87
IL23/IL23R/JAK2/TYK2	-0.3	0.74	-10000	0	-1.6	87	87
IL6	-0.33	0.66	-10000	0	-1.4	123	123
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.001	0.017	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.009	0.036	1	-10000	0	1
CD3E	-0.23	0.58	-10000	0	-1.3	87	87
keratinocyte proliferation	-0.25	0.62	-10000	0	-1.4	87	87
NOS2	-0.21	0.51	-10000	0	-1.1	88	88

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.62	75	75
FYN	-0.1	0.35	-10000	0	-0.83	77	77
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.66	85	85
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.052	0.22	-10000	0	-0.47	87	87
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.03	0.049	-10000	0	-0.15	31	31
MAP3K8	0	0.1	-10000	0	-0.82	8	8
mol:Ca2+	-0.03	0.05	-10000	0	-0.12	106	106
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.1	0.32	-10000	0	-0.74	87	87
TRPV6	-0.17	0.34	-10000	0	-0.8	108	108
CD28	-0.042	0.19	-10000	0	-0.58	45	45
SHC1	-0.11	0.34	-10000	0	-0.8	83	83
receptor internalization	-0.14	0.38	-10000	0	-0.84	90	90
PRF1	-0.11	0.35	-10000	0	-0.88	71	71
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.035	0.18	-10000	0	-0.38	85	85
LAT	-0.11	0.35	-10000	0	-0.82	83	83
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.092	0.27	-10000	0	-0.72	71	71
CD3E	-0.068	0.24	-10000	0	-0.76	52	52
CD3G	-0.15	0.32	-10000	0	-0.78	98	98
RASGRP2	0	0.031	-10000	0	-0.19	6	6
RASGRP1	-0.048	0.22	-10000	0	-0.47	89	89
HLA-A	0.011	0.021	-10000	0	-0.31	2	2
RASSF5	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.068	-10000	0	-0.12	66	66
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.056	0.089	-10000	0	-0.25	59	59
PRKCA	-0.061	0.13	-10000	0	-0.31	89	89
GRAP2	-0.041	0.2	-10000	0	-0.77	34	34
mol:IP3	-0.05	0.23	0.27	85	-0.47	83	168
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.15	0.42	-10000	0	-0.97	80	80
ORAI1	0.087	0.16	0.39	101	-10000	0	101
CSK	-0.12	0.35	-10000	0	-0.82	83	83
B7 family/CD28	-0.19	0.34	-10000	0	-0.74	112	112
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.15	0.42	-10000	0	-1	83	83
PTPN6	-0.12	0.36	-10000	0	-0.84	82	82
VAV1	-0.12	0.34	-10000	0	-0.79	87	87
Monovalent TCR/CD3	-0.16	0.4	-10000	0	-0.73	118	118
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.88	78	78
PAG1	-0.12	0.35	-10000	0	-0.83	83	83
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.15	0.42	-10000	0	-0.99	83	83
CD80	-0.069	0.25	-10000	0	-0.8	49	49
CD86	-0.008	0.1	-10000	0	-0.42	24	24
PDK1/CARD11/BCL10/MALT1	-0.068	0.11	-10000	0	-0.3	69	69
HRAS	0.012	0.021	-10000	0	-0.31	2	2
GO:0035030	-0.1	0.29	-10000	0	-0.58	112	112
CD8A	-0.047	0.22	-10000	0	-0.82	35	35
CD8B	-0.087	0.27	-10000	0	-0.73	67	67
PTPRC	-0.033	0.17	-10000	0	-0.6	36	36
PDK1/PKC theta	-0.066	0.27	-10000	0	-0.6	85	85
CSK/PAG1	-0.1	0.34	-10000	0	-0.84	76	76
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.015	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.15	0.32	-10000	0	-0.78	87	87
STIM1	0.046	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.009	0.091	-10000	0	-0.18	60	60
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.43	-10000	0	-0.94	90	90
mol:DAG	-0.07	0.18	-10000	0	-0.41	86	86
RAP1A/GDP	0.006	0.029	-10000	0	-0.063	12	12
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.02	0.16	-10000	0	-0.63	26	26
cytotoxic T cell degranulation	-0.1	0.33	-10000	0	-0.83	71	71
RAP1A/GTP	-0.003	0.009	-10000	0	-0.07	5	5
mol:PI-3-4-5-P3	-0.071	0.26	-10000	0	-0.58	87	87
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.078	0.29	0.3	76	-0.62	86	162
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.022	0.16	-10000	0	-0.6	28	28
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.25	-10000	0	-0.63	86	86
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.01	0.053	-10000	0	-0.82	2	2
CD8 heterodimer	-0.1	0.29	-10000	0	-0.76	71	71
CARD11	-0.073	0.17	-10000	0	-0.35	116	116
PRKCB	-0.058	0.13	-10000	0	-0.3	87	87
PRKCE	-0.051	0.12	-10000	0	-0.3	73	73
PRKCQ	-0.088	0.31	-10000	0	-0.69	86	86
LCP2	0.009	0.039	-10000	0	-0.31	7	7
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.039	0.18	-10000	0	-0.4	87	87
IKK complex	0.013	0.069	-10000	0	-0.12	55	55
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.016	0.14	-10000	0	-0.3	69	69
PDPK1	-0.045	0.21	-10000	0	-0.45	85	85
TCR/CD3/MHC I/CD8/Fyn	-0.16	0.45	-10000	0	-1.1	82	82

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.088	0.15	-9999	-0.31	152	152
GPC2	-0.01	0.084	-9999	-0.31	35	35
GPC2/Midkine	-0.077	0.11	-9999	-0.4	13	13
neuron projection morphogenesis	-0.077	0.11	-9999	-0.4	13	13

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.042	0.11	-9999	-0.47	13	13
EGFR	0.006	0.075	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
USP6	0.011	0.026	-9999	-0.31	3	3
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.097	0.22	-9999	-0.63	74	74
ARRB2	-0.043	0.15	-9999	-0.45	59	59
mol:GTP	0.021	0.012	-9999	-10000	0	0
ARRB1	0.012	0.038	-9999	-0.82	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.01	0.053	-9999	-0.82	2	2
EGF	-0.11	0.29	-9999	-0.78	76	76
somatostatin receptor activity	0	0	-9999	-0.001	141	141
ARAP2	0.01	0.053	-9999	-0.82	2	2
mol:GDP	-0.12	0.15	-9999	-0.29	160	160
mol:PI-3-4-5-P3	0	0	-9999	-0.001	131	131
ITGA2B	-0.072	0.25	-9999	-0.82	50	50
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
ADAP1	0.013	0	-9999	-10000	0	0
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.17	0.24	-9999	-0.68	74	74
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.12	0.15	-9999	-0.31	141	141
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.084	0.19	-9999	-0.54	74	74
ADRB2	-0.009	0.13	-9999	-0.82	13	13
receptor agonist activity	0	0	-9999	0	153	153
actin filament binding	0	0	-9999	-0.001	141	141
SRC	0.013	0.015	-9999	-0.31	1	1
ITGB3	-0.01	0.14	-9999	-0.82	14	14
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	136	136
ARF6/GDP	0	0.068	-9999	-0.33	2	2
ARF6/GDP/GULP/ACAP1	-0.18	0.2	-9999	-0.5	110	110
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.064	0.18	-9999	-0.53	59	59
ACAP1	0.001	0.076	-9999	-0.38	16	16
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.08	0.22	-9999	-0.67	59	59
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.11	0.3	-9999	-0.82	74	74
CYTH3	0.009	0.041	-9999	-0.64	2	2
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	138	138
endosomal lumen acidification	0	0	-9999	-0.001	153	153
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.32	-9999	-0.82	88	88
GNAQ/ARNO	0.009	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	45	45
MET	-0.11	0.16	-9999	-0.31	179	179
GNA14	-0.18	0.35	-9999	-0.82	114	114
GNA15	-0.014	0.095	-9999	-0.33	39	39
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	140	140
GNA11	-0.004	0.12	-9999	-0.82	10	10
LHCGR	-0.097	0.27	-9999	-0.76	66	66
AGTR1	-0.32	0.41	-9999	-0.81	196	196
desensitization of G-protein coupled receptor protein signaling pathway	-0.079	0.22	-9999	-0.67	59	59
IPCEF1/ARNO	-0.056	0.16	-9999	-0.43	74	74
alphaIIb/beta3 Integrin	-0.081	0.22	-9999	-0.67	59	59

×

BMP receptor signaling

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.26	0.32	-9999	-0.59	216	216
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.046	0.21	-9999	-0.69	41	41
SMAD9	-0.22	0.28	-9999	-0.59	164	164
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.093	0.2	-9999	-0.56	27	27
BMP7/USAG1	-0.32	0.31	-9999	-0.63	252	252
SMAD5/SKI	-0.081	0.19	-9999	-0.52	27	27
SMAD1	0.02	0.044	-9999	-10000	0	0
BMP2	-0.019	0.16	-9999	-0.82	19	19
SMAD1/SMAD1/SMAD4	-0.001	0.001	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.26	0.39	-9999	-0.82	160	160
BMPR1A-1B/BAMBI	-0.18	0.26	-9999	-0.55	160	160
AHSG	-0.019	0.087	-9999	-0.31	39	39
CER1	0	0.003	-9999	-10000	0	0
BMP2-4/CER1	-0.038	0.14	-9999	-0.55	32	32
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.075	0.19	-9999	-0.61	31	31
BMP2-4 (homodimer)	-0.044	0.16	-9999	-0.63	32	32
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	160	160
RGMA	-0.016	0.15	-9999	-0.82	17	17
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.086	0.18	-9999	-0.57	28	28
BMP2-4/USAG1	-0.32	0.3	-9999	-0.57	268	268
SMAD6/SMURF1/SMAD5	-0.081	0.19	-9999	-0.52	27	27
SOSTDC1	-0.42	0.41	-9999	-0.81	253	253
BMP7/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.49	160	160
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.013	0.015	-9999	-0.31	1	1
HFE2	0.001	0.033	-9999	-0.31	5	5
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.049	0.16	-9999	-0.55	41	41
SMAD5/SMAD5/SMAD4	-0.081	0.19	-9999	-0.52	27	27
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.092	0.14	-9999	-0.48	28	28
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.017	0.057	-9999	-0.4	1	1
SMAD1/SKI	0.026	0.042	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.05	0.14	-9999	-0.56	32	32
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.2	0.35	-9999	-0.72	143	143
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.008	0.064	-9999	-0.54	7	7
BMPR1A-1B (homodimer)	-0.2	0.29	-9999	-0.63	160	160
CHRDL1	-0.57	0.38	-9999	-0.82	346	346
ENDOFIN/SMAD1	0.026	0.042	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.006	0.008	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.002	0.081	-9999	-0.36	20	20
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.42	0.28	-9999	-0.58	352	352
BMP2-4/GREM1	-0.17	0.28	-9999	-0.6	134	134
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.19	0.28	-9999	-0.55	164	164
SMAD1/SMAD6	0.026	0.042	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.013	0	-9999	-10000	0	0
BMP6	0.013	0.015	-9999	-0.31	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.065	0.16	-9999	-0.49	28	28
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.026	0.042	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.001	0.099	-9999	-0.82	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.19	0.31	-9999	-0.79	84	84
CHRD	-0.004	0.12	-9999	-0.82	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.091	0.19	-9999	-0.6	28	28
BMP4	-0.013	0.14	-9999	-0.64	20	20
FST	-0.19	0.35	-9999	-0.78	127	127
BMP2-4/NOG	-0.075	0.18	-9999	-0.55	63	63
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.15	0.22	-9999	-0.46	160	160

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.087	0.2	-10000	0	-0.56	76	76
cell-cell adhesion	0.15	0.18	0.54	11	-10000	0	11
Ephrin B/EPHB2/RasGAP	-0.014	0.068	-10000	0	-0.46	10	10
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.081	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.21	0.27	-10000	0	-0.55	190	190
HRAS/GDP	-0.13	0.17	-10000	0	-0.49	13	13
Ephrin B/EPHB1/GRB7	-0.21	0.24	-10000	0	-0.5	195	195
Endophilin/SYNJ1	0.025	0.071	-10000	0	-0.43	10	10
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.19	0.23	-10000	0	-0.47	195	195
endothelial cell migration	-0.003	0.036	-10000	0	-0.46	3	3
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.033	0.072	-10000	0	-0.43	10	10
HRAS	0.012	0.021	-10000	0	-0.31	2	2
RRAS	0.025	0.073	-10000	0	-0.44	10	10
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.16	0.24	-10000	0	-0.45	195	195
lamellipodium assembly	-0.15	0.18	-10000	0	-0.54	11	11
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.11	0.18	-10000	0	-0.33	190	190
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.065	-10000	0	-0.82	3	3
EPHB3	-0.19	0.16	-10000	0	-0.31	298	298
EPHB1	-0.31	0.4	-10000	0	-0.82	190	190
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.07	0.17	-10000	0	-0.46	11	11
Ephrin B/EPHB2	-0.014	0.069	-10000	0	-0.47	10	10
Ephrin B/EPHB3	-0.086	0.087	-10000	0	-0.57	7	7
JNK cascade	-0.15	0.24	-10000	0	-0.45	192	192
Ephrin B/EPHB1	-0.19	0.23	-10000	0	-0.48	195	195
RAP1/GDP	-0.054	0.15	-10000	0	-0.43	7	7
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.011	0.12	-10000	0	-0.45	25	25
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.25	-10000	0	-0.5	192	192
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.16	0.19	-10000	0	-0.51	18	18
Rap1/GTP	-0.15	0.18	-10000	0	-0.55	11	11
axon guidance	-0.086	0.2	-10000	0	-0.55	76	76
MAPK3	-0.08	0.16	-10000	0	-0.38	11	11
MAPK1	-0.08	0.16	-10000	0	-0.38	11	11
Rac1/GDP	-0.046	0.17	-10000	0	-0.46	7	7
actin cytoskeleton reorganization	-0.11	0.13	-10000	0	-0.45	6	6
CDC42/GDP	-0.046	0.17	-10000	0	-0.46	7	7
PI3K	-0.003	0.036	-10000	0	-0.47	3	3
EFNA5	-0.11	0.3	-10000	0	-0.81	75	75
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.055	-10000	0	-0.33	10	10
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.15	0.18	-10000	0	-0.53	12	12
PTK2	0.042	0.052	-10000	0	-10000	0	0
MAP4K4	-0.15	0.24	-10000	0	-0.46	192	192
SRC	0.013	0.015	-10000	0	-0.31	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.07	0.18	-10000	0	-0.54	3	3
MAP2K1	-0.092	0.17	-10000	0	-0.3	190	190
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.19	0.24	-10000	0	-0.49	192	192
cell migration	-0.088	0.19	-10000	0	-0.35	60	60
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.025	0.072	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.021	0.17	-10000	0	-0.44	61	61
HRAS/GTP	-0.16	0.2	-10000	0	-0.4	197	197
Ephrin B1/EPHB1-2	-0.2	0.25	-10000	0	-0.5	192	192
cell adhesion mediated by integrin	0.013	0.075	0.5	7	-10000	0	7
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.18	0.21	-10000	0	-0.43	197	197
RAC1-CDC42/GTP	-0.21	0.21	-10000	0	-0.49	147	147
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.054	0.15	-10000	0	-0.52	3	3
ruffle organization	-0.11	0.22	-10000	0	-0.55	11	11
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.018	0.11	-10000	0	-0.45	24	24
Ephrin B/EPHB2/KALRN	-0.014	0.068	-10000	0	-0.46	10	10
ROCK1	-0.074	0.081	-10000	0	-10000	0	0
RAS family/GDP	-0.084	0.11	-10000	0	-0.52	3	3
Rac1/GTP	-0.16	0.2	-10000	0	-0.58	11	11
Ephrin B/EPHB1/Src/Paxillin	-0.11	0.18	-10000	0	-0.33	195	195

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.015	0.064	-10000	0	-0.36	13	13
SVIL	-0.006	0.031	-10000	0	-10000	0	0
ZNF318	0.061	0.093	-10000	0	-0.82	1	1
JMJD2C	-0.065	0.069	-10000	0	-0.12	279	279
T-DHT/AR/Ubc9	-0.28	0.3	-10000	0	-0.62	205	205
CARM1	0.012	0.003	-10000	0	-10000	0	0
PRDX1	0.015	0.004	-10000	0	-10000	0	0
PELP1	0.02	0.011	-10000	0	-10000	0	0
CTNNB1	-0.002	0.023	-10000	0	-10000	0	0
AKT1	0.026	0.019	-10000	0	-10000	0	0
PTK2B	0.004	0.015	-10000	0	-10000	0	0
MED1	0.025	0.019	-10000	0	-10000	0	0
MAK	0.05	0.13	0.22	5	-0.8	7	12
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.06	-10000	0	-0.82	2	2
GSN	-0.006	0.03	-10000	0	-10000	0	0
NCOA2	-0.068	0.24	-10000	0	-0.82	47	47
NCOA6	-0.007	0.047	-10000	0	-0.82	1	1
DNA-PK	0.058	0.084	-10000	0	-10000	0	0
NCOA4	0.011	0.004	-10000	0	-10000	0	0
PIAS3	-0.002	0.023	-10000	0	-10000	0	0
cell proliferation	-0.012	0.15	-10000	0	-1	7	7
XRCC5	0.025	0.018	-10000	0	-10000	0	0
UBE3A	-0.016	0.047	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.31	0.33	-10000	0	-0.66	213	213
FHL2	-0.16	0.36	-10000	0	-1.3	39	39
RANBP9	-0.005	0.029	-10000	0	-10000	0	0
JMJD1A	0.003	0.037	-10000	0	-0.12	36	36
CDK6	0.009	0.065	-10000	0	-0.82	3	3
TGFB1I1	-0.006	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.29	0.3	-10000	0	-0.63	208	208
XRCC6	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR	-0.33	0.32	-10000	0	-0.63	231	231
CTDSP1	0.009	0.006	-10000	0	-10000	0	0
CTDSP2	0.046	0.05	-10000	0	-10000	0	0
BRCA1	-0.006	0.031	-10000	0	-10000	0	0
TCF4	0.035	0.034	-10000	0	-10000	0	0
CDKN2A	-0.11	0.16	-10000	0	-0.31	142	142
SRF	0.028	0.039	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-1.3	4	4
KLK3	-0.44	0.71	-10000	0	-1.6	138	138
TMF1	0.006	0.053	-10000	0	-0.82	2	2
HNRNPA1	0.031	0.028	-10000	0	-10000	0	0
AOF2	-0.022	0.034	-10000	0	-0.075	138	138
APPL1	0.052	0.042	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.27	0.29	-10000	0	-0.61	205	205
AR	-0.38	0.42	-10000	0	-0.86	205	205
UBA3	0.009	0.006	-10000	0	-10000	0	0
PATZ1	0.031	0.028	-10000	0	-10000	0	0
PAWR	0.009	0.006	-10000	0	-10000	0	0
PRKDC	0.025	0.018	-10000	0	-10000	0	0
PA2G4	0.036	0.036	-10000	0	-10000	0	0
UBE2I	0.013	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.25	0.28	-10000	0	-0.56	205	205
RPS6KA3	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.28	0.29	-10000	0	-0.62	205	205
LATS2	0.029	0.047	-10000	0	-0.82	1	1
T-DHT/AR/PRX1	-0.24	0.28	-10000	0	-0.56	205	205
Cyclin D3/CDK11 p58	0	0.003	-10000	0	-10000	0	0
VAV3	-0.012	0.093	-10000	0	-0.82	6	6
KLK2	-0.77	0.62	-10000	0	-1.3	278	278
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.67	212	212
TMPRSS2	-0.19	0.31	-10000	0	-1.3	33	33
CCND1	0.001	0.051	-10000	0	-0.31	12	12
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.032	0.041	-10000	0	-0.082	164	164
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.036	0.077	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.28	0.3	-10000	0	-0.62	207	207
CMTM2	0.014	0.026	-10000	0	-0.31	3	3
SNURF	-0.037	0.2	-10000	0	-0.82	29	29
ZMIZ1	-0.013	0.051	-10000	0	-0.8	1	1
CCND3	0.014	0.002	-10000	0	-10000	0	0
TGIF1	0.031	0.028	-10000	0	-10000	0	0
FKBP4	-0.005	0.029	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.044	-9999	-0.31	9	9
CCL5	-0.043	0.2	-9999	-0.71	38	38
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.16	-9999	-0.49	47	47
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.092	0.15	-9999	-0.63	22	22
Syndecan-1/Syntenin	-0.092	0.15	-9999	-0.63	22	22
MAPK3	-0.069	0.14	-9999	-0.6	19	19
HGF/MET	-0.17	0.24	-9999	-0.68	74	74
TGFB1/TGF beta receptor Type II	0.007	0.044	-9999	-0.31	9	9
BSG	0.013	0.015	-9999	-0.31	1	1
keratinocyte migration	-0.09	0.15	-9999	-0.62	22	22
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.66	51	51
Syndecan-1/CD147	-0.081	0.15	-9999	-0.6	22	22
Syndecan-1/Syntenin/PIP2	-0.099	0.14	-9999	-0.61	22	22
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.097	0.14	-9999	-0.59	22	22
MMP7	-0.18	0.22	-9999	-0.37	246	246
HGF	-0.11	0.3	-9999	-0.82	74	74
Syndecan-1/CASK	-0.1	0.15	-9999	-0.47	47	47
Syndecan-1/HGF/MET	-0.2	0.24	-9999	-0.64	87	87
regulation of cell adhesion	-0.059	0.14	-9999	-0.57	19	19
HPSE	-0.017	0.14	-9999	-0.51	28	28
positive regulation of cell migration	-0.1	0.16	-9999	-0.49	47	47
SDC1	-0.11	0.16	-9999	-0.49	47	47
Syndecan-1/Collagen	-0.1	0.16	-9999	-0.49	47	47
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	179	179
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.081	0.24	-9999	-0.57	79	79
MAPK1	-0.069	0.14	-9999	-0.6	19	19
homophilic cell adhesion	-0.1	0.16	-9999	-0.48	47	47
MMP1	-0.14	0.16	-9999	-0.31	232	232

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.06	0.21	-10000	0	-0.63	29	29
CRP	-0.065	0.22	-10000	0	-0.63	32	32
cell cycle arrest	-0.082	0.24	-10000	0	-0.71	35	35
TIMP1	-0.16	0.22	-10000	0	-0.59	45	45
IL6ST	-0.11	0.29	-10000	0	-0.82	71	71
Rac1/GDP	-0.09	0.25	-10000	0	-0.61	61	61
AP1	-0.19	0.32	-10000	0	-0.7	123	123
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.1	0.23	-10000	0	-0.66	25	25
HSP90B1	0.022	0.043	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
MAPK14	-0.1	0.3	-10000	0	-0.8	57	57
AKT1	0.053	0.057	-10000	0	-1.1	1	1
FOXO1	0.059	0.053	-10000	0	-0.98	1	1
MAP2K6	-0.11	0.29	-10000	0	-0.63	82	82
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.078	0.24	-10000	0	-0.63	48	48
MITF	-0.093	0.26	-10000	0	-0.58	72	72
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.013	0	-10000	0	-10000	0	0
A2M	0.025	0.006	-10000	0	-10000	0	0
CEBPB	0.022	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.023	0.086	-10000	0	-0.49	1	1
STAT3	-0.095	0.25	-10000	0	-0.76	36	36
STAT1	-0.011	0.023	-10000	0	-10000	0	0
CEBPD	-0.06	0.21	-10000	0	-0.63	29	29
PIK3CA	0.01	0.065	-10000	0	-0.82	3	3
PI3K	0.019	0.051	-10000	0	-0.62	3	3
JUN	-0.17	0.35	-10000	0	-0.82	110	110
PIAS3/MITF	-0.08	0.25	-10000	0	-0.62	54	54
MAPK11	-0.1	0.3	-10000	0	-0.77	61	61
STAT3 (dimer)/FOXO1	-0.011	0.2	-10000	0	-0.57	23	23
GRB2/SOS1/GAB family	-0.12	0.2	-10000	0	-0.68	33	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.26	-10000	0	-0.47	127	127
GRB2	0.014	0	-10000	0	-10000	0	0
JAK2	0.01	0.053	-10000	0	-0.82	2	2
LBP	-0.063	0.2	-10000	0	-0.6	16	16
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.014	0.005	-10000	0	-10000	0	0
MYC	-0.075	0.27	-10000	0	-0.89	28	28
FGG	-0.069	0.22	-10000	0	-0.65	28	28
macrophage differentiation	-0.082	0.24	-10000	0	-0.71	35	35
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.18	0.29	-10000	0	-0.56	155	155
JUNB	-0.065	0.23	-10000	0	-0.71	30	30
FOS	-0.2	0.36	-10000	0	-0.82	128	128
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.1	0.28	-10000	0	-0.5	122	122
STAT1/PIAS1	-0.085	0.24	-10000	0	-0.53	73	73
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.061	-10000	0	-0.59	3	3
STAT3 (dimer)	-0.092	0.24	-10000	0	-0.74	35	35
PRKCD	-0.066	0.23	-10000	0	-0.63	41	41
IL6R	-0.017	0.16	-10000	0	-0.82	18	18
SOCS3	-0.12	0.37	-10000	0	-1	54	54
gp130 (dimer)/JAK1/JAK1/LMO4	-0.06	0.2	-10000	0	-0.54	71	71
Rac1/GTP	-0.11	0.24	-10000	0	-0.62	61	61
HCK	-0.008	0.08	-10000	0	-0.31	31	31
MAPKKK cascade	0.009	0.077	-10000	0	-0.98	1	1
bone resorption	-0.097	0.22	-10000	0	-0.62	28	28
IRF1	-0.06	0.21	-10000	0	-0.63	28	28
mol:GDP	-0.1	0.26	-10000	0	-0.58	78	78
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.1	0.27	-10000	0	-0.6	77	77
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.3	-10000	0	-0.8	58	58
PTPN11	-0.011	0.059	-10000	0	-1.2	1	1
IL6/IL6RA	-0.15	0.28	-10000	0	-0.66	109	109
gp130 (dimer)/TYK2/TYK2/LMO4	-0.065	0.2	-10000	0	-0.54	71	71
gp130 (dimer)/JAK2/JAK2/LMO4	-0.067	0.2	-10000	0	-0.56	71	71
IL6	-0.17	0.33	-10000	0	-0.71	124	124
PIAS3	0.013	0	-10000	0	-10000	0	0
PTPRE	-0.079	0.15	-10000	0	-0.32	133	133
PIAS1	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.26	-10000	0	-0.46	142	142
LMO4	0.012	0.009	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.11	0.23	0.38	1	-0.75	35	36
MCL1	0.059	0.048	-10000	0	-0.88	1	1

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.022	0.16	-10000	0	-0.45	27	27
TBX21	-0.11	0.43	-10000	0	-1	66	66
B2M	0.012	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.02	-10000	0	-10000	0	0
IL12RB1	-0.019	0.12	-10000	0	-0.42	24	24
GADD45B	-0.086	0.38	-10000	0	-0.97	55	55
IL12RB2	-0.015	0.16	-10000	0	-0.72	21	21
GADD45G	-0.069	0.34	-10000	0	-0.92	44	44
natural killer cell activation	0.003	0.022	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	-0.035	0.15	-10000	0	-0.41	58	58
IL2RA	-0.045	0.19	-10000	0	-0.57	49	49
IFNG	-0.11	0.28	-10000	0	-0.72	78	78
STAT3 (dimer)	-0.068	0.32	-10000	0	-0.74	64	64
HLA-DRB5	-0.041	0.13	-10000	0	-0.35	70	70
FASLG	-0.13	0.46	-10000	0	-1.2	65	65
NF kappa B2 p52/RelB	-0.16	0.32	-10000	0	-0.86	66	66
CD4	0	0.059	-10000	0	-0.32	16	16
SOCS1	0.009	0.048	-10000	0	-0.82	1	1
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.096	0.27	-10000	0	-0.72	71	71
CD3E	-0.072	0.24	-10000	0	-0.75	52	52
CD3G	-0.15	0.32	-10000	0	-0.79	98	98
IL12Rbeta2/JAK2	-0.002	0.13	-10000	0	-0.63	19	19
CCL3	-0.1	0.42	-10000	0	-1.1	51	51
CCL4	-0.15	0.51	-10000	0	-1.3	66	66
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
IL18/IL18R	-0.028	0.19	-10000	0	-0.56	45	45
NOS2	-0.083	0.34	-10000	0	-0.81	60	60
IL12/IL12R/TYK2/JAK2/SPHK2	-0.02	0.15	-10000	0	-0.42	29	29
IL1R1	-0.082	0.37	-10000	0	-0.96	51	51
IL4	0.001	0.022	-10000	0	-10000	0	0
JAK2	0.013	0.057	-10000	0	-0.83	2	2
EntrezGene:6957	-0.006	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.56	-10000	0	-1.2	103	103
RAB7A	-0.037	0.29	-10000	0	-0.69	48	48
lysosomal transport	-0.032	0.28	-10000	0	-0.65	50	50
FOS	-0.4	0.65	-10000	0	-1.3	162	162
STAT4 (dimer)	-0.072	0.35	-10000	0	-0.82	61	61
STAT5A (dimer)	-0.21	0.36	-10000	0	-0.87	91	91
GZMA	-0.1	0.41	-10000	0	-1	56	56
GZMB	-0.097	0.39	-10000	0	-1	51	51
HLX	0.004	0.055	-10000	0	-0.31	14	14
LCK	-0.1	0.42	-10000	0	-0.97	69	69
TCR/CD3/MHC II/CD4	-0.19	0.34	-10000	0	-0.74	99	99
IL2/IL2R	-0.08	0.21	-10000	0	-0.65	47	47
MAPK14	-0.064	0.35	-10000	0	-0.8	64	64
CCR5	-0.093	0.4	-10000	0	-1.2	43	43
IL1B	-0.053	0.23	-10000	0	-0.78	43	43
STAT6	-0.003	0.11	-10000	0	-10000	0	0
STAT4	-0.024	0.14	-10000	0	-0.46	39	39
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.048	-10000	0	-0.31	11	11
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	0	0.095	-10000	0	-0.55	11	11
CD8A	-0.047	0.22	-10000	0	-0.82	35	35
CD8B	-0.088	0.26	-10000	0	-0.72	67	67
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.022	0.16	0.45	27	-10000	0	27
IL2RB	-0.015	0.13	-10000	0	-0.5	27	27
proteasomal ubiquitin-dependent protein catabolic process	-0.061	0.32	-10000	0	-0.74	61	61
IL2RG	-0.047	0.19	-10000	0	-0.54	53	53
IL12	-0.056	0.21	-10000	0	-0.63	56	56
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.024	0.15	-10000	0	-0.63	26	26
IL2	0.004	0.006	-10000	0	-10000	0	0
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.074	0.26	-10000	0	-0.8	54	54
IL12/IL12R/TYK2/JAK2	-0.12	0.47	-10000	0	-1	71	71
MAP2K3	-0.066	0.34	-10000	0	-0.78	65	65
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.073	0.35	-10000	0	-0.82	64	64
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.027	0.13	-10000	0	-0.82	7	7
IL18RAP	-0.019	0.17	-10000	0	-0.8	21	21
IL12Rbeta1/TYK2	-0.003	0.093	-10000	0	-0.64	4	4
EOMES	-0.15	0.43	-10000	0	-1.5	44	44
STAT1 (dimer)	-0.13	0.36	-10000	0	-0.77	93	93
T cell proliferation	-0.045	0.27	-10000	0	-0.61	56	56
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.026	0.14	-10000	0	-0.42	47	47
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.24	-10000	0	-0.69	59	59
ATF2	-0.069	0.33	-10000	0	-0.75	61	61

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.002	0.046	-9999	-1	1	1
forebrain development	-0.32	0.29	-9999	-0.56	253	253
GNAO1	-0.02	0.15	-9999	-0.82	16	16
SMO/beta Arrestin2	0.011	0.031	-9999	-0.62	1	1
SMO	0.006	0.038	-9999	-0.82	1	1
ARRB2	0.008	0.007	-9999	-10000	0	0
GLI3/SPOP	0.044	0.056	-9999	-10000	0	0
mol:GTP	-0.002	0.003	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.01	0.006	-9999	-10000	0	0
SIN3/HDAC complex	0.009	0.029	-9999	-0.49	1	1
GNAI1	0.008	0.038	-9999	-0.83	1	1
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.24	0.19	-9999	-0.51	135	135
SAP30	0.012	0.038	-9999	-0.82	1	1
mol:GDP	0.006	0.038	-9999	-0.81	1	1
MIM/GLI2A	-0.007	0.043	-9999	-0.31	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GLI2	0.033	0.061	-9999	-10000	0	0
GLI3	0.039	0.059	-9999	-10000	0	0
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.012	0.038	-9999	-0.82	1	1
Gi family/GTP	0.007	0.07	-9999	-0.33	18	18
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.029	0.05	-9999	-10000	0	0
GLI2/Su(fu)	0.023	0.058	-9999	-10000	0	0
FOXA2	-0.66	0.66	-9999	-1.3	236	236
neural tube patterning	-0.32	0.29	-9999	-0.56	253	253
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.022	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	-0.007	0.043	-9999	-0.31	1	1
embryonic limb morphogenesis	-0.32	0.29	-9999	-0.56	253	253
SUFU	0.016	0.021	-9999	-10000	0	0
LGALS3	-0.1	0.16	-9999	-0.31	171	171
catabolic process	0.061	0.068	-9999	-10000	0	0
GLI3A/CBP	-0.19	0.2	-9999	-0.38	253	253
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.32	0.29	-9999	-0.57	253	253
RAB23	0.007	0.075	-9999	-0.82	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.034	0.079	-9999	-0.4	1	1
GNAZ	0.01	0.006	-9999	-10000	0	0
RBBP4	0.009	0.065	-9999	-0.82	3	3
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.057	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.013	0.063	-9999	-0.54	1	1
PTCH1	-0.28	0.27	-9999	-0.62	135	135
MIM/GLI1	-0.45	0.39	-9999	-0.76	248	248
CREBBP	-0.19	0.2	-9999	-0.38	253	253
Su(fu)/SIN3/HDAC complex	0.056	0.027	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.11	0.39	-9999	-1.3	43	43
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.035	0.11	-9999	-0.39	19	19
ATF2/c-Jun	-0.22	0.42	-9999	-0.97	111	111
MAPK11	-0.035	0.11	-9999	-0.39	19	19
MITF	-0.029	0.13	-9999	-0.4	43	43
MAPKAPK5	-0.029	0.13	-9999	-0.47	19	19
KRT8	-0.029	0.13	-9999	-0.4	43	43
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.048	0.17	-9999	-0.51	43	43
CEBPB	-0.029	0.13	-9999	-0.4	43	43
SLC9A1	-0.029	0.13	-9999	-0.4	43	43
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.072	0.19	-9999	-0.54	39	39
p38alpha-beta/MNK1	-0.024	0.14	-9999	-0.49	19	19
JUN	-0.22	0.42	-9999	-0.96	111	111
PPARGC1A	-0.23	0.25	-9999	-0.46	256	256
USF1	-0.029	0.13	-9999	-0.47	19	19
RAB5/GDP/GDI1	-0.038	0.083	-9999	-0.35	19	19
NOS2	-0.048	0.16	-9999	-0.54	19	19
DDIT3	-0.031	0.13	-9999	-0.4	43	43
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.012	0.11	-9999	-0.39	18	18
p38alpha-beta/HBP1	-0.024	0.14	-9999	-0.49	19	19
CREB1	-0.049	0.16	-9999	-0.46	43	43
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.015	0.12	-9999	-0.44	18	18
RPS6KA4	-0.029	0.13	-9999	-0.47	19	19
PLA2G4A	-0.048	0.2	-9999	-0.6	44	44
GDI1	-0.029	0.13	-9999	-0.4	43	43
TP53	-0.037	0.16	-9999	-0.5	43	43
RPS6KA5	-0.079	0.2	-9999	-0.46	89	89
ESR1	-0.064	0.21	-9999	-0.55	55	55
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.029	0.13	-9999	-0.4	44	44
MEF2A	-0.029	0.13	-9999	-0.4	44	44
EIF4EBP1	-0.049	0.16	-9999	-0.45	44	44
KRT19	-0.1	0.2	-9999	-0.54	55	55
ELK4	-0.029	0.13	-9999	-0.47	19	19
ATF6	-0.029	0.13	-9999	-0.4	43	43
ATF1	-0.05	0.16	-9999	-0.47	44	44
p38alpha-beta/MAPKAPK2	-0.024	0.14	-9999	-0.49	19	19
p38alpha-beta/MAPKAPK3	-0.024	0.14	-9999	-0.49	19	19

×

Syndecan-4-mediated 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
PTK2	-0.082	0.062	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.18	-9999	-0.64	40	40
positive regulation of JNK cascade	-0.16	0.2	-9999	-0.6	68	68
Syndecan-4/ADAM12	-0.17	0.18	-9999	-0.64	42	42
CCL5	-0.043	0.2	-9999	-0.71	38	38
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
PLG	-0.001	0.039	-9999	-0.29	8	8
ADAM12	-0.068	0.14	-9999	-0.31	121	121
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.065	0.045	-9999	-0.23	4	4
Syndecan-4/Laminin alpha1	-0.17	0.21	-9999	-0.68	49	49
Syndecan-4/CXCL12/CXCR4	-0.17	0.22	-9999	-0.65	68	68
Syndecan-4/Laminin alpha3	-0.15	0.19	-9999	-0.66	45	45
MDK	-0.088	0.15	-9999	-0.31	152	152
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.64	42	42
Syndecan-4/Midkine	-0.18	0.19	-9999	-0.64	42	42
FZD7	0.007	0.075	-9999	-0.82	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.59	41	41
THBS1	-0.011	0.086	-9999	-0.31	37	37
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.66	41	41
positive regulation of MAPKKK cascade	-0.16	0.2	-9999	-0.6	68	68
Syndecan-4/TACI	-0.24	0.26	-9999	-0.63	120	120
CXCR4	0.012	0.021	-9999	-0.31	2	2
cell adhesion	-0.068	0.096	-9999	-0.44	23	23
Syndecan-4/Dynamin	-0.13	0.18	-9999	-0.64	40	40
Syndecan-4/TSP1	-0.14	0.18	-9999	-0.64	41	41
Syndecan-4/GIPC	-0.13	0.18	-9999	-0.64	40	40
Syndecan-4/RANTES	-0.16	0.22	-9999	-0.74	48	48
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.049	0.22	-9999	-0.8	37	37
LAMA3	-0.026	0.16	-9999	-0.58	32	32
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.015	0.17	-9999	-0.74	23	23
Syndecan-4/alpha-Actinin	-0.13	0.18	-9999	-0.64	40	40
TFPI	-0.033	0.19	-9999	-0.82	27	27
F2	-0.007	0.053	-9999	-0.31	14	14
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.17	0.21	-9999	-0.66	55	55
ACTN1	0.013	0.015	-9999	-0.31	1	1
TNC	-0.11	0.17	-9999	-0.32	184	184
Syndecan-4/CXCL12	-0.18	0.23	-9999	-0.68	68	68
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.072	0.25	-9999	-0.82	50	50
TNFRSF13B	-0.19	0.35	-9999	-0.79	120	120
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.012	0.038	-9999	-0.82	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.65	40	40
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.32	335	335
cell migration	-0.022	0.017	-9999	-10000	0	0
PRKCD	0.008	0.015	-9999	-10000	0	0
vasculogenesis	-0.14	0.17	-9999	-0.61	41	41
SDC4	-0.15	0.19	-9999	-0.69	40	40
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.69	41	41
Syndecan-4/PI-4-5-P2/PKC alpha	-0.051	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.18	-9999	-0.64	40	40
MMP9	-0.083	0.24	-9999	-0.57	78	78
Rac1/GTP	-0.074	0.094	-9999	-0.46	23	23
cytoskeleton organization	-0.13	0.17	-9999	-0.62	40	40
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.2	-9999	-0.64	57	57

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.043	0.12	-9999	-0.46	28	28
alphaM/beta2 Integrin/GPIbA	-0.053	0.14	-9999	-0.57	26	26
alphaM/beta2 Integrin/proMMP-9	-0.091	0.19	-9999	-0.58	54	54
PLAUR	-0.09	0.15	-9999	-0.31	155	155
HMGB1	0.002	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.034	0.098	-9999	-0.43	20	20
AGER	-0.059	0.22	-9999	-0.78	38	38
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.007	0.08	-9999	-0.31	31	31
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.12	0.19	-9999	-0.6	46	46
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.081	0.24	-9999	-0.57	79	79
CYR61	-0.24	0.38	-9999	-0.82	147	147
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.072	0.09	-9999	-0.39	14	14
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.003	0.1	-9999	-0.58	13	13
MYH2	-0.1	0.12	-9999	-0.46	16	16
MST1R	0.001	0.095	-9999	-0.65	9	9
leukocyte activation during inflammatory response	-0.04	0.093	-9999	-0.42	14	14
APOB	-0.011	0.08	-9999	-0.31	32	32
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.001	0.1	-9999	-0.63	11	11
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	-0.018	0.15	-9999	-0.64	23	23
alphaM/beta2 Integrin/CTGF	-0.11	0.22	-9999	-0.56	89	89
alphaM/beta2 Integrin	-0.095	0.11	-9999	-0.35	47	47
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.083	0.15	-9999	-0.31	144	144
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.094	0.11	-9999	-0.34	47	47
cell adhesion	-0.053	0.14	-9999	-0.56	26	26
NFKB1	-0.13	0.29	-9999	-0.71	65	65
THY1	0.011	0.029	-9999	-0.31	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.014	0.05	-9999	-0.34	2	2
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.1	-9999	-0.48	16	16
IL6	-0.23	0.46	-9999	-1	104	104
ITGB2	-0.018	0.086	-9999	-0.34	28	28
elevation of cytosolic calcium ion concentration	-0.14	0.16	-9999	-0.5	42	42
alphaM/beta2 Integrin/JAM2/JAM3	-0.031	0.1	-9999	-0.49	15	15
JAM2	0.006	0.076	-9999	-0.72	5	5
alphaM/beta2 Integrin/ICAM1	-0.067	0.12	-9999	-0.5	22	22
alphaM/beta2 Integrin/uPA/Plg	-0.099	0.12	-9999	-0.51	21	21
RhoA/GTP	-0.11	0.12	-9999	-0.42	39	39
positive regulation of phagocytosis	-0.07	0.12	-9999	-0.46	20	20
Ron/MSP	-0.011	0.076	-9999	-0.63	7	7
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.16	-9999	-0.5	42	42
alphaM/beta2 Integrin/uPAR	-0.085	0.13	-9999	-0.45	35	35
PLAU	-0.14	0.16	-9999	-0.31	226	226
PLAT	0.001	0.085	-9999	-0.48	12	12
actin filament polymerization	-0.1	0.11	-9999	-0.44	16	16
MST1	0.011	0.04	-9999	-0.56	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.04	0.094	-9999	-0.45	11	11
TNF	-0.18	0.39	-9999	-0.97	81	81
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.13	-9999	-0.44	38	38
fibrinolysis	-0.098	0.12	-9999	-0.5	21	21
HCK	-0.007	0.08	-9999	-0.31	31	31
dendritic cell antigen processing and presentation	-0.094	0.11	-9999	-0.34	47	47
VTN	-0.068	0.24	-9999	-0.75	52	52
alphaM/beta2 Integrin/CYR61	-0.2	0.27	-9999	-0.57	161	161
LPA	-0.002	0.043	-9999	-0.31	9	9
LRP1	0.012	0.038	-9999	-0.82	1	1
cell migration	-0.088	0.19	-9999	-0.57	57	57
FN1	-0.22	0.15	-9999	-0.31	354	354
alphaM/beta2 Integrin/Thy1	-0.035	0.099	-9999	-0.42	21	21
MPO	0.001	0.087	-9999	-0.63	8	8
KNG1	-0.015	0.079	-9999	-0.31	32	32
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.094	0.12	-9999	-0.42	24	24
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.04	-9999	-0.31	8	8
CTGF	-0.11	0.29	-9999	-0.82	72	72
alphaM/beta2 Integrin/Hck	-0.044	0.12	-9999	-0.47	30	30
ITGAM	-0.023	0.11	-9999	-0.39	31	31
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.046	0.13	-9999	-0.52	26	26
HP	-0.082	0.16	-9999	-0.82	6	6
leukocyte adhesion	-0.091	0.16	-9999	-0.6	27	27
SELP	-0.003	0.1	-9999	-0.58	13	13

×

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	-0.093	0.22	-9999	-0.41	145	145
MAP3K8	-0.003	0.11	-9999	-0.82	8	8
FOS	-0.058	0.17	-9999	-0.45	44	44
PRKCA	-0.028	0.18	-9999	-0.82	23	23
PTPN7	-0.044	0.17	-9999	-0.46	57	57
HRAS	0.011	0.021	-9999	-0.31	2	2
PRKCB	-0.03	0.13	-9999	-0.36	53	53
NRAS	0.013	0.002	-9999	-10000	0	0
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.03	0.12	-9999	-0.41	28	28
MAP2K1	-0.025	0.15	-9999	-0.56	30	30
ELK1	0.008	0.01	-9999	-10000	0	0
BRAF	-0.045	0.13	-9999	-0.57	27	27
mol:GTP	-0.001	0.003	-9999	-0.006	127	127
MAPK1	-0.03	0.12	-9999	-0.41	28	28
RAF1	-0.045	0.13	-9999	-0.57	27	27
KRAS	0.013	0.002	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.033	0.11	-10000	0	-0.31	67	67
GNB1/GNG2	-0.045	0.068	-10000	0	-0.2	48	48
AKT1	-0.013	0.1	-10000	0	-0.21	40	40
EGF	-0.11	0.29	-10000	0	-0.78	76	76
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.031	0.076	-10000	0	-0.64	2	2
mol:Ca2+	-0.044	0.15	-10000	0	-0.31	75	75
LYN	0.032	0.075	-10000	0	-0.64	2	2
RhoA/GTP	-0.031	0.045	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.044	0.16	-10000	0	-0.35	73	73
GNG2	0.012	0.038	-10000	0	-0.82	1	1
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.55	12	12
G beta5/gamma2	-0.06	0.092	-10000	0	-0.27	49	49
PRKCH	-0.052	0.16	-10000	0	-0.36	72	72
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
TXA2/TP beta/beta Arrestin3	-0.013	0.055	-10000	0	-0.3	16	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.022	0.17	-10000	0	-0.82	21	21
G12 family/GTP	-0.078	0.11	-10000	0	-0.31	73	73
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.013	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.1	0.35	16	-10000	0	16
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.22	0.37	-10000	0	-0.82	134	134
mol:IP3	-0.06	0.18	-10000	0	-0.39	75	75
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.088	0.23	-10000	0	-0.53	75	75
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.096	0.2	-10000	0	-0.39	143	143
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.024	0.08	-10000	0	-0.64	2	2
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.003	0.091	-10000	0	-0.82	6	6
PRKCB1	-0.06	0.17	-10000	0	-0.39	75	75
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.085	0.23	-10000	0	-0.54	76	76
LCK	0.022	0.096	-10000	0	-0.54	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.019	0.089	-10000	0	-0.96	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.031	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.019	0.088	-10000	0	-0.95	2	2
MAPK14	-0.019	0.11	-10000	0	-0.23	46	46
TGM2/GTP	-0.073	0.2	-10000	0	-0.43	76	76
MAPK11	-0.019	0.11	-10000	0	-0.23	47	47
ARHGEF1	-0.015	0.089	-10000	0	-0.19	23	23
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.057	0.18	-10000	0	-0.39	77	77
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.052	0.15	-10000	0	-0.3	79	79
cAMP biosynthetic process	-0.059	0.17	-10000	0	-0.36	74	74
Gq family/GTP/EBP50	-0.044	0.12	-10000	0	-0.25	121	121
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.032	0.075	-10000	0	-0.64	2	2
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.018	0.1	-10000	0	-0.31	16	16
VCAM1	-0.038	0.14	-10000	0	-0.3	75	75
TP beta/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.55	12	12
platelet activation	-0.026	0.15	-10000	0	-0.3	72	72
PGI2/IP	-0.008	0.07	-10000	0	-0.64	6	6
PRKACA	-0.001	0.11	-10000	0	-0.43	25	25
Gq family/GDP/G beta5/gamma2	-0.028	0.12	-10000	0	-0.5	12	12
TXA2/TP beta/beta Arrestin2	-0.023	0.12	-10000	0	-0.66	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.007	0.11	-10000	0	-0.41	25	25
mol:DAG	-0.068	0.19	-10000	0	-0.44	75	75
EGFR	0.007	0.075	-10000	0	-0.82	4	4
TXA2/TP alpha	-0.083	0.22	-10000	0	-0.5	74	74
Gq family/GTP	-0.076	0.13	-10000	0	-0.3	121	121
YES1	0.032	0.075	-10000	0	-0.64	2	2
GNAI2/GTP	-0.017	0.077	-10000	0	-0.8	2	2
PGD2/DP	-0.027	0.13	-10000	0	-0.64	21	21
SLC9A3R1	0.012	0.021	-10000	0	-0.31	2	2
FYN	0.032	0.075	-10000	0	-0.64	2	2
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.014	0.095	-10000	0	-0.33	39	39
PGK/cGMP	-0.15	0.24	-10000	0	-0.55	134	134
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.031	0.1	-10000	0	-0.66	6	6
NOS3	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.064	0.18	-10000	0	-0.4	80	80
PRKCB	-0.062	0.17	-10000	0	-0.38	76	76
PRKCE	-0.055	0.17	-10000	0	-0.38	74	74
PRKCD	-0.055	0.17	-10000	0	-0.39	73	73
PRKCG	-0.059	0.18	-10000	0	-0.4	74	74
muscle contraction	-0.075	0.22	-10000	0	-0.5	75	75
PRKCZ	-0.044	0.16	-10000	0	-0.35	73	73
ARR3	0.004	0.006	-10000	0	-10000	0	0
TXA2/TP beta	-0.019	0.09	-10000	0	-0.98	2	2
PRKCQ	-0.053	0.17	-10000	0	-0.36	76	76
MAPKKK cascade	-0.075	0.2	-10000	0	-0.47	76	76
SELE	-0.058	0.18	-10000	0	-0.43	74	74
TP beta/GNAI2/GDP/G beta/gamma	-0.019	0.093	-10000	0	-1.1	2	2
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.35	-10000	0	-0.82	114	114
chemotaxis	-0.098	0.26	-10000	0	-0.62	75	75
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	-0.004	0.12	-10000	0	-0.82	10	10
Rac1/GTP	0.002	0.004	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.021	-9999	-0.31	2	2
EGFR	0.007	0.075	-9999	-0.82	4	4
EGF/EGFR	-0.076	0.17	-9999	-0.45	80	80
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.071	0.16	-9999	-0.46	74	74
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.009	0.048	-9999	-0.41	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	76	76
EGF/EGFR dimer/SHC	-0.084	0.19	-9999	-0.54	74	74
mol:GDP	-0.07	0.16	-9999	-0.45	74	74
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.004	0.085	-9999	-0.73	6	6
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.065	0.15	-9999	-0.42	74	74
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.066	0.15	-9999	-0.43	74	74
FRAP1	-0.035	0.17	-9999	-0.44	74	74
EGF/EGFR dimer	-0.097	0.22	-9999	-0.63	74	74
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.01	0.072	-9999	-0.63	6	6

×

TCGA08_p53

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
CDKN2A	-0.085	0.11	-9999	-0.21	210	210
TP53	-0.028	0.033	-9999	-10000	0	0
Senescence	-0.028	0.033	-9999	-10000	0	0
Apoptosis	-0.028	0.033	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.054	0.062	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.032	0.14	-9999	-0.46	37	37
NF kappa B1 p50/RelA/I kappa B alpha	-0.054	0.11	-9999	-0.53	7	7
alphaV/beta3 Integrin/Osteopontin/Src	-0.066	0.15	-9999	-0.61	24	24
AP1	-0.26	0.35	-9999	-0.85	108	108
ILK	-0.032	0.15	-9999	-0.49	37	37
bone resorption	-0.048	0.15	-9999	-0.64	12	12
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.051	0.12	-9999	-0.44	37	37
ITGAV	0.01	0.053	-9999	-0.81	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.031	0.14	-9999	-0.63	24	24
alphaV/beta3 Integrin/Osteopontin	-0.069	0.15	-9999	-0.55	37	37
MAP3K1	-0.032	0.15	-9999	-0.5	37	37
JUN	-0.17	0.35	-9999	-0.82	110	110
MAPK3	-0.032	0.15	-9999	-0.46	37	37
MAPK1	-0.032	0.15	-9999	-0.46	37	37
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.032	0.17	-9999	-0.5	44	44
ITGB3	-0.01	0.14	-9999	-0.81	14	14
NFKBIA	-0.025	0.14	-9999	-0.58	7	7
FOS	-0.2	0.36	-9999	-0.82	128	128
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.11	0.17	-9999	-0.69	4	4
NF kappa B1 p50/RelA	-0.06	0.11	-9999	-0.57	4	4
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.02	0.12	-9999	-0.65	15	15
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.032	0.15	-9999	-0.5	37	37
VAV3	-0.026	0.15	-9999	-0.47	42	42
MAP3K14	-0.04	0.15	-9999	-0.5	37	37
ROCK2	-0.027	0.18	-9999	-0.82	24	24
SPP1	-0.082	0.2	-9999	-0.41	109	109
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.054	0.12	-9999	-0.52	12	12
MMP2	-0.18	0.29	-9999	-0.66	100	100

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.025	0.078	0.29	36	-10000	0	36
RFC1	0.025	0.078	0.29	36	-10000	0	36
PRKDC	0.025	0.078	0.29	36	-10000	0	36
RIPK1	0.014	0.004	-10000	0	-10000	0	0
CASP7	-0.013	0.044	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.027	0.099	0.26	5	-0.37	31	36
MAP2K4	-0.022	0.16	-10000	0	-0.53	15	15
mol:ceramide	-0.02	0.14	-10000	0	-0.48	32	32
GSN	0.025	0.078	0.29	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 8	-0.017	0.13	-10000	0	-0.47	31	31
FAS	0.011	0.006	-10000	0	-10000	0	0
BID	-0.032	0.08	0.32	3	-10000	0	3
MAP3K1	0.005	0.097	-10000	0	-10000	0	0
MAP3K7	0.01	0.006	-10000	0	-10000	0	0
RB1	0.024	0.078	0.29	35	-0.31	1	36
CFLAR	0.014	0.004	-10000	0	-10000	0	0
HGF/MET	-0.14	0.22	-10000	0	-0.61	77	77
ARHGDIB	0.022	0.081	0.29	36	-10000	0	36
FADD	0.011	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.025	0.077	-10000	0	-0.29	36	36
NFKB1	-0.052	0.093	-10000	0	-0.32	16	16
MAPK8	-0.058	0.22	-10000	0	-0.45	96	96
DFFA	0.025	0.078	0.29	36	-10000	0	36
DNA fragmentation during apoptosis	0.025	0.077	0.29	36	-10000	0	36
FAS/FADD/MET	-0.058	0.077	-10000	0	-10000	0	0
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.088	-10000	0	-0.39	20	20
FAF1	0.011	0.007	-10000	0	-10000	0	0
PARP1	0.025	0.078	0.29	36	-10000	0	36
DFFB	0.025	0.078	0.29	36	-10000	0	36
CHUK	-0.045	0.082	-10000	0	-0.73	1	1
FASLG	-0.055	0.21	-10000	0	-0.66	48	48
FAS/FADD	0	0.001	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	74	74
LMNA	0.023	0.071	0.26	36	-10000	0	36
CASP6	0.025	0.078	0.29	36	-10000	0	36
CASP10	0.011	0.006	-10000	0	-10000	0	0
CASP3	0.03	0.094	0.34	39	-10000	0	39
PTPN13	0.003	0.091	-10000	0	-0.82	6	6
CASP8	0.008	0.044	0.45	3	-10000	0	3
IL6	-0.26	0.56	-10000	0	-1.4	98	98
MET	-0.11	0.16	-10000	0	-0.31	179	179
ICAD/CAD	0.023	0.072	0.27	36	-10000	0	36
FASLG/FAS/FADD/FAF1/Caspase 10	-0.021	0.14	-10000	0	-0.49	32	32
activation of caspase activity by cytochrome c	-0.032	0.079	0.32	3	-10000	0	3
PAK2	0.025	0.077	0.29	36	-10000	0	36
BCL2	-0.047	0.22	-10000	0	-0.82	36	36

×

Regulation of Androgen receptor activity

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
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.013	0.014	-9999	-10000	0	0
REL	-0.037	0.21	-9999	-0.81	33	33
HDAC7	-0.034	0.15	-9999	-0.64	17	17
JUN	-0.18	0.34	-9999	-0.82	110	110
EP300	0.013	0.001	-9999	-10000	0	0
KAT2B	0.013	0.001	-9999	-10000	0	0
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.003	0.098	-9999	-0.64	11	11
FOXO1	0.012	0.001	-9999	-10000	0	0
T-DHT/AR	-0.046	0.16	-9999	-0.67	18	18
MAP2K6	-0.011	0.12	-9999	-0.78	12	12
BRM/BAF57	-0.002	0.003	-9999	-10000	0	0
MAP2K4	0.009	0.007	-9999	-10000	0	0
SMARCA2	0.009	0.007	-9999	-10000	0	0
PDE9A	0.011	0.058	-9999	-10000	0	0
NCOA2	-0.074	0.24	-9999	-0.82	47	47
CEBPA	0.006	0.084	-9999	-0.82	5	5
EHMT2	0.009	0.006	-9999	-10000	0	0
cell proliferation	-0.069	0.15	-9999	-0.52	21	21
NR0B1	-0.002	0.041	-9999	-0.31	8	8
EGR1	-0.17	0.34	-9999	-0.82	104	104
RXRs/9cRA	-0.13	0.058	-9999	-0.5	4	4
AR/RACK1/Src	-0.12	0.16	-9999	-0.67	19	19
AR/GR	-0.13	0.2	-9999	-0.38	128	128
GNB2L1	0.007	0.007	-9999	-10000	0	0
PKN1	0.013	0.001	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.006	0.005	-9999	-10000	0	0
MAPK8	-0.002	0.097	-9999	-0.64	11	11
T-DHT/AR/TIF2/CARM1	-0.13	0.24	-9999	-0.7	55	55
SRC	-0.005	0.12	-9999	-0.55	19	19
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.4	0.57	-9999	-1.3	139	139
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.056	0.15	-9999	-0.68	19	19
TMPRSS2	-0.059	0.32	-9999	-1.2	32	32
RXRG	-0.28	0.12	-9999	-0.32	433	433
mol:9cRA	-0.002	0.002	-9999	-10000	0	0
RXRA	0.012	0.001	-9999	-10000	0	0
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.007	0.007	-9999	-10000	0	0
NR2C2	-0.006	0.12	-9999	-0.82	11	11
KLK2	-0.48	0.43	-9999	-0.83	288	288
AR	-0.15	0.22	-9999	-0.38	206	206
SENP1	0.012	0.002	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.022	0.014	-9999	-10000	0	0
SRY	0.01	0.015	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
MYST2	0.014	0.002	-9999	-10000	0	0
HOXB13	-0.015	0.054	-9999	-0.32	13	13
T-DHT/AR/RACK1/Src	-0.079	0.15	-9999	-0.67	19	19
positive regulation of transcription	0.013	0.015	-9999	-0.31	1	1
DNAJA1	0.013	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.005	-9999	-10000	0	0
NCOA1	0.013	0.009	-9999	-10000	0	0
SPDEF	-0.028	0.1	-9999	-0.32	55	55
T-DHT/AR/TIF2	-0.056	0.16	-9999	-0.46	49	49
T-DHT/AR/Hsp90	-0.058	0.15	-9999	-0.68	19	19
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.008	0.12	-9999	-0.59	19	19
SIRT1	0.011	0.038	-9999	-0.82	1	1
ZMIZ2	0.023	0.015	-9999	-10000	0	0
POU2F1	0.031	0.019	-9999	-0.3	1	1
T-DHT/AR/DAX-1	-0.077	0.14	-9999	-0.68	19	19
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.009	0.007	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.12	0.1	-9999	-0.65	7	7
EPHB2	0.008	0.065	-9999	-0.82	3	3
Syndecan-2/TACI	-0.12	0.25	-9999	-0.56	118	118
LAMA1	-0.049	0.22	-9999	-0.8	37	37
Syndecan-2/alpha2 ITGB1	-0.071	0.11	-9999	-0.46	24	24
HRAS	0.012	0.021	-9999	-0.31	2	2
Syndecan-2/CASK	-0.008	0.065	-9999	-0.55	7	7
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.023	0.1	-9999	-0.75	2	2
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.007	0.059	-9999	-0.49	7	7
LAMA3	-0.026	0.16	-9999	-0.58	32	32
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.065	-9999	-0.82	3	3
Syndecan-2/MMP2	0.008	0.1	-9999	-0.58	13	13
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.078	0.098	-9999	-10000	0	0
dendrite morphogenesis	0.014	0.08	-9999	-0.54	10	10
Syndecan-2/GM-CSF	-0.11	0.098	-9999	-0.56	7	7
determination of left/right symmetry	0.012	0.077	-9999	-0.62	7	7
Syndecan-2/PKC delta	0.018	0.067	-9999	-0.54	7	7
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.087	0.091	-9999	-0.51	7	7
MAPK1	-0.087	0.091	-9999	-0.51	7	7
Syndecan-2/RACK1	-0.007	0.056	-9999	-0.46	7	7
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.077	-9999	-0.62	7	7
ITGA2	-0.11	0.16	-9999	-0.31	188	188
MAPK8	0.015	0.11	-9999	-0.55	18	18
Syndecan-2/alpha2/beta1 Integrin	-0.085	0.14	-9999	-0.51	40	40
Syndecan-2/Kininogen	-0.008	0.078	-9999	-0.55	7	7
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.031	0.057	-9999	-0.43	7	7
Syndecan-2/CASK/Protein 4.1	-0.007	0.059	-9999	-0.5	7	7
extracellular matrix organization	0.014	0.071	-9999	-0.54	7	7
actin cytoskeleton reorganization	-0.12	0.1	-9999	-0.64	7	7
Syndecan-2/Caveolin-2/Ras	-0.011	0.076	-9999	-0.54	9	9
Syndecan-2/Laminin alpha3	-0.008	0.12	-9999	-0.54	24	24
Syndecan-2/RasGAP	-0.007	0.053	-9999	-0.44	7	7
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.014	0.08	-9999	-0.54	10	10
GO:0007205	0.004	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.056	-9999	-0.42	7	7
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.19	0.35	-9999	-0.79	120	120
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.078	0.098	-9999	-10000	0	0
Syndecan-2/Synbindin	0.018	0.067	-9999	-0.54	7	7
TGFB1	0.007	0.044	-9999	-0.31	9	9
CASP3	0.027	0.062	-9999	-0.49	7	7
FN1	-0.22	0.15	-9999	-0.31	354	354
Syndecan-2/IL8	-0.037	0.12	-9999	-0.54	17	17
SDC2	0.012	0.077	-9999	-0.62	7	7
KNG1	-0.015	0.079	-9999	-0.31	32	32
Syndecan-2/Neurofibromin	0.018	0.067	-9999	-0.54	7	7
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.21	0.15	-9999	-0.31	332	332
Syndecan-2/TGFB1	0.014	0.071	-9999	-0.54	7	7
Syndecan-2/Syntenin/PI-4-5-P2	-0.007	0.059	-9999	-0.5	7	7
Syndecan-2/Ezrin	-0.007	0.058	-9999	-0.49	7	7
PRKACA	0.027	0.062	-9999	-0.49	7	7
angiogenesis	-0.037	0.12	-9999	-0.54	17	17
MMP2	-0.001	0.1	-9999	-0.63	11	11
IL8	-0.081	0.17	-9999	-0.35	125	125
calcineurin-NFAT signaling pathway	-0.12	0.25	-9999	-0.55	118	118

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.006	0.12	-9999	-0.77	12	12
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.15	0.15	-9999	-0.28	283	283
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.011	0.029	-9999	-0.31	4	4
p38 alpha/TAB1	-0.047	0.067	-9999	-0.31	4	4
PRKG1	-0.22	0.37	-9999	-0.82	134	134
DUSP8	0.004	0.074	-9999	-0.48	9	9
PGK/cGMP/p38 alpha	-0.16	0.2	-9999	-0.46	136	136
apoptosis	-0.046	0.065	-9999	-0.3	4	4
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.12	0.31	-9999	-0.82	79	79
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1/OSM/MEKK3/MKK3	-0.001	0.008	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.82	2	2
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.012	0.021	-9999	-0.31	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.06	0.13	-9999	-0.36	16	16
BLK	-0.24	0.37	-9999	-0.75	165	165
HCK	-0.007	0.08	-9999	-0.31	31	31
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.01	0.043	-9999	-0.48	3	3
TRAF6/MEKK3	-0.002	0.032	-9999	-0.51	2	2
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.027	0.091	-9999	-0.32	5	5
positive regulation of innate immune response	-0.058	0.14	-9999	-0.39	13	13
LCK	-0.01	0.11	-9999	-0.43	26	26
p38alpha-beta/MKP7	-0.049	0.13	-9999	-0.44	5	5
p38alpha-beta/MKP5	-0.05	0.13	-9999	-0.48	6	6
PGK/cGMP	-0.17	0.28	-9999	-0.64	134	134
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.11	0.2	-9999	-0.47	83	83
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.47	0.41	-9999	-0.82	283	283

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.035	0.12	-10000	0	-0.5	26	26
ER alpha/Gai/GDP/Gbeta gamma	0.006	0.15	-10000	0	-0.54	24	24
AKT1	-0.014	0.2	-10000	0	-0.86	25	25
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.013	0.2	-10000	0	-0.87	25	25
mol:Ca2+	-0.1	0.23	-10000	0	-0.49	116	116
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.071	0.18	-10000	0	-0.58	52	52
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.012	0.19	0.81	25	-10000	0	25
RhoA/GTP	-0.026	0.088	-10000	0	-0.41	23	23
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.036	0.13	-10000	0	-0.59	23	23
regulation of stress fiber formation	-0.012	0.12	0.46	5	-10000	0	5
E2/ERA-ERB (dimer)	-0.041	0.13	-10000	0	-0.57	26	26
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.034	0.11	-10000	0	-0.5	23	23
pseudopodium formation	0.012	0.12	-10000	0	-0.46	5	5
E2/ER alpha (dimer)/PELP1	-0.037	0.12	-10000	0	-0.55	23	23
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.82	1	1
GNAO1	-0.017	0.15	-10000	0	-0.82	16	16
HRAS	0.012	0.021	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.012	0.15	-10000	0	-0.59	24	24
E2/ER beta (dimer)	-0.005	0.057	-10000	0	-0.64	4	4
mol:GDP	-0.035	0.13	-10000	0	-0.56	26	26
mol:NADP	0.012	0.15	-10000	0	-0.59	24	24
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.1	0.24	-10000	0	-0.52	116	116
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.11	0.24	-10000	0	-0.54	116	116
PLCB2	-0.12	0.25	-10000	0	-0.54	115	115
IGF1	-0.18	0.35	-10000	0	-0.82	113	113
mol:L-citrulline	0.012	0.15	-10000	0	-0.59	24	24
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.026	0.14	-10000	0	-0.78	16	16
JNK cascade	-0.005	0.057	-10000	0	-0.63	4	4
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.007	0.075	-10000	0	-0.82	4	4
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.047	0.19	-10000	0	-0.52	55	55
Gq family/GDP/Gbeta gamma	-0.057	0.18	-10000	0	-0.54	23	23
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.08	-10000	0	-0.33	23	23
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.036	0.13	-10000	0	-0.59	23	23
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.044	0.14	-10000	0	-0.64	23	23
STRN	-0.039	0.2	-10000	0	-0.82	31	31
GNAL	-0.09	0.27	-10000	0	-0.82	61	61
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.015	0.051	-10000	0	-0.55	4	4
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
HBEGF	-0.004	0.16	-10000	0	-0.66	15	15
cAMP biosynthetic process	-0.088	0.18	-10000	0	-0.48	83	83
SRC	0.014	0.14	-10000	0	-0.5	24	24
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.031	0.11	-10000	0	-0.5	26	26
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-10000	0	-0.52	38	38
Gs family/GTP	-0.09	0.19	-10000	0	-0.49	83	83
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	0.013	0.14	-10000	0	-0.56	24	24
mol:DAG	-0.1	0.24	-10000	0	-0.52	116	116
Gs family/GDP/Gbeta gamma	-0.072	0.16	-10000	0	-0.51	27	27
MSN	0.01	0.12	-10000	0	-0.5	5	5
Gq family/GTP	-0.15	0.24	-10000	0	-0.57	115	115
mol:PI-3-4-5-P3	-0.011	0.19	-10000	0	-0.83	25	25
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.013	0.14	0.56	24	-10000	0	24
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.032	0.12	-10000	0	-0.52	26	26
NOS3	0.011	0.16	-10000	0	-0.63	24	24
GNA11	-0.004	0.12	-10000	0	-0.82	10	10
MAPKKK cascade	-0.008	0.19	-10000	0	-0.54	52	52
E2/ER alpha (dimer)/PELP1/Src	-0.039	0.14	-10000	0	-0.62	23	23
ruffle organization	0.012	0.12	-10000	0	-0.46	5	5
ROCK2	0.001	0.14	-10000	0	-0.4	46	46
GNA14	-0.18	0.35	-10000	0	-0.82	114	114
GNA15	-0.014	0.095	-10000	0	-0.33	39	39
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.026	0.19	-10000	0	-0.51	46	46
MMP2	0.015	0.15	-10000	0	-0.68	11	11

×

Visual signal transduction: Rods

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
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.017	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.011	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.018	0.07	-9999	-0.55	5	5
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.026	-9999	-0.31	3	3
GRK1	-0.066	0.24	-9999	-0.81	47	47
CNG Channel	-0.028	0.084	-9999	-0.51	9	9
mol:Na +	-0.023	0.081	-9999	-0.45	13	13
mol:ADP	-0.066	0.24	-9999	-0.8	47	47
RGS9-1/Gbeta5/R9AP	-0.089	0.2	-9999	-0.55	78	78
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.023	0.083	-9999	-0.46	13	13
CNGB1	-0.001	0.063	-9999	-0.31	19	19
RDH5	-0.2	0.16	-9999	-0.31	315	315
SAG	0.002	0.015	-9999	-0.31	1	1
mol:Ca2+	0.016	0.088	-9999	-0.54	3	3
Na + (4 Units)	-0.021	0.075	-9999	-0.47	5	5
RGS9	-0.076	0.26	-9999	-0.82	52	52
GNB1/GNGT1	-0.003	0.024	-9999	-10000	0	0
GNAT1/GDP	-0.078	0.18	-9999	-0.48	78	78
GUCY2D	-0.01	0.11	-9999	-0.82	6	6
GNGT1	-0.004	0.037	-9999	-0.31	7	7
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.073	-9999	-0.47	5	5
mol:11-cis-retinal	-0.2	0.16	-9999	-0.31	315	315
mol:cGMP	-0.016	0.071	-9999	-0.48	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.13	0.099	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0.001	0.089	-9999	-0.56	10	10
Metarhodopsin II	-0.049	0.15	-9999	-0.51	46	46
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.075	-9999	-0.5	9	9
RGS9BP	-0.034	0.19	-9999	-0.82	28	28
Metarhodopsin II/Transducin	0.011	0.015	-9999	-10000	0	0
GCAP Family/Ca ++	-0.005	0.043	-9999	-0.51	3	3
PDE6A/B	-0.012	0.048	-9999	-10000	0	0
mol:Pi	-0.089	0.2	-9999	-0.55	78	78
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.023	-9999	-10000	0	0
PDE6B	0.013	0	-9999	-10000	0	0
PDE6A	-0.008	0.077	-9999	-0.31	29	29
PDE6G	-0.017	0.12	-9999	-0.38	37	37
RHO	0.006	0.016	-9999	-0.31	1	1
PDE6	-0.09	0.18	-9999	-0.48	81	81
GUCA1A	0.004	0.033	-9999	-0.31	5	5
GC2/GCAP Family	-0.005	0.043	-9999	-0.51	3	3
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.008	0.066	-9999	-0.69	4	4

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.074	0.097	-10000	0	-10000	0	0
CRKL	-0.031	0.11	-10000	0	-0.33	25	25
mol:PIP3	-0.019	0.032	0.68	1	-10000	0	1
AKT1	0.001	0.04	0.45	1	-0.53	2	3
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	-0.022	0.11	-10000	0	-10000	0	0
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
HGF/MET/SHIP2	-0.14	0.2	-10000	0	-0.59	74	74
MAP3K5	-0.018	0.11	-10000	0	-0.47	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.19	-10000	0	-0.54	74	74
AP1	-0.28	0.42	-10000	0	-0.87	151	151
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.26	0.4	-10000	0	-0.86	151	151
STAT3 (dimer)	-0.04	0.13	-10000	0	-0.33	74	74
GAB1/CRKL/SHP2/PI3K	-0.043	0.094	-10000	0	-0.59	3	3
INPP5D	-0.003	0.072	-10000	0	-0.31	25	25
CBL/CRK	-0.022	0.11	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1
ELK1	-0.049	0.062	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.04	0.072	-10000	0	-0.24	26	26
PAK1	0.009	0.037	0.42	1	-0.5	2	3
HGF/MET/RANBP10	-0.14	0.2	-10000	0	-0.59	74	74
HRAS	-0.059	0.16	-10000	0	-0.48	26	26
DOCK1	-0.026	0.12	-10000	0	-0.55	4	4
GAB1	-0.041	0.12	-10000	0	-0.3	74	74
CRK	-0.031	0.11	-10000	0	-0.33	25	25
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.11	0.21	-10000	0	-0.6	74	74
JUN	-0.17	0.35	-10000	0	-0.82	110	110
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.071	0.1	-10000	0	-0.29	74	74
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.012	0.14	-10000	0	-0.65	2	2
GRB2/SHC	-0.039	0.096	-10000	0	-0.3	25	25
FOS	-0.2	0.36	-10000	0	-0.82	128	128
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.048	0.062	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.14	0.21	-10000	0	-0.6	74	74
cell migration	-0.038	0.095	-10000	0	-0.3	25	25
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.074	0.097	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.051	0.14	-10000	0	-0.36	74	74
MET/MUC20	-0.078	0.1	-10000	0	-10000	0	0
RAP1B	-0.013	0.1	-10000	0	-10000	0	0
RAP1A	-0.013	0.1	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.14	0.2	-10000	0	-0.59	74	74
RAF1	-0.048	0.15	-10000	0	-0.45	26	26
STAT3	-0.04	0.13	-10000	0	-0.34	74	74
cell proliferation	-0.048	0.18	-10000	0	-0.45	74	74
RPS6KB1	-0.015	0.039	-10000	0	-10000	0	0
MAPK3	-0.05	0.057	-10000	0	-10000	0	0
MAPK1	-0.05	0.057	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.008	0.14	-10000	0	-0.57	15	15
SRC	-0.04	0.13	-10000	0	-0.39	25	25
PI3K	-0.042	0.1	-10000	0	-0.32	28	28
MET/Glomulin	-0.058	0.093	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.037	0.14	-10000	0	-0.41	26	26
MET	-0.11	0.16	-10000	0	-0.31	179	179
MAP4K1	-0.027	0.12	-10000	0	-0.33	31	31
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.037	0.14	-10000	0	-0.41	26	26
BAD	0.009	0.037	0.42	1	-0.5	2	3
MAP2K4	-0.009	0.1	-10000	0	-0.42	5	5
SHP2/GRB2/SOS1/GAB1	-0.057	0.09	-10000	0	-0.38	1	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	-0.049	0.1	-10000	0	-0.32	25	25
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	74	74
RASA1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.041	0.11	-10000	0	-0.33	25	25
PDPK1	-0.009	0.043	0.51	1	-0.57	2	3
HGF/MET/SHIP	-0.15	0.21	-10000	0	-0.6	74	74

×

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	0.037	0.039	-9999	-10000	0	0
VDR	0.013	0.015	-9999	-0.31	1	1
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.059	0.11	-9999	-0.35	48	48
RXRs/LXRs/DNA/Oxysterols	-0.048	0.16	-9999	-0.46	58	58
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.021	0.084	-9999	-0.34	24	24
RXRs/NUR77	-0.26	0.25	-9999	-0.63	145	145
RXRs/PPAR	-0.055	0.064	-9999	-0.4	11	11
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.014	0.08	-9999	-0.48	14	14
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-9999	-0.31	1	1
RARs/RARs/DNA/9cRA	-0.013	0.079	-9999	-0.47	14	14
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.054	0.032	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.021	0.084	-9999	-0.34	24	24
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0.01	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.082	-9999	-0.58	4	4
NR1H4	0.001	0.033	-9999	-10000	0	0
RXRs/LXRs/DNA	-0.099	0.092	-9999	-0.57	4	4
NR1H2	0.016	0.012	-9999	-10000	0	0
NR1H3	0.015	0.014	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.067	-9999	-0.52	4	4
NR4A1	-0.23	0.38	-9999	-0.81	143	143
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.047	0.049	-9999	-0.34	3	3
RXRG	-0.28	0.12	-9999	-0.32	433	433
RXR alpha/CCPG	0.021	0.01	-9999	-10000	0	0
RXRA	0.015	0.012	-9999	-10000	0	0
RXRB	0.015	0.014	-9999	-10000	0	0
THRB	-0.005	0.12	-9999	-0.82	11	11
PPARG	-0.002	0.1	-9999	-0.82	7	7
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.41	-9999	-1.3	58	58
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.048	0.15	-9999	-0.45	58	58
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.14	-9999	-0.82	14	14
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.45	168	168
SREBF1	-0.038	0.14	-9999	-0.62	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.082	-9999	-0.58	4	4
ABCA1	-0.037	0.14	-9999	-0.62	3	3
RARs/THRs	-0.023	0.1	-9999	-0.48	24	24
RXRs/FXR	-0.12	0.071	-9999	-0.55	4	4
BCL2	-0.048	0.22	-9999	-0.82	36	36

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.044	-10000	0	-0.31	9	9
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.066	0.15	0.55	10	-10000	0	10
IL27/IL27R/JAK1	-0.12	0.19	-10000	0	-0.57	51	51
TBX21	-0.09	0.22	-10000	0	-0.63	35	35
IL12B	-0.004	0.09	-10000	0	-0.54	11	11
IL12A	-0.059	0.2	-10000	0	-0.61	54	54
IL6ST	-0.11	0.29	-10000	0	-0.82	71	71
IL27RA/JAK1	0.013	0.026	-10000	0	-10000	0	0
IL27	0.002	0.037	-10000	0	-0.32	6	6
TYK2	0.012	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.062	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.066	0.15	0.55	10	-10000	0	10
T cell proliferation during immune response	0.066	0.15	0.55	10	-10000	0	10
MAPKKK cascade	-0.066	0.15	-10000	0	-0.55	10	10
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.049	-10000	0	-0.32	11	11
IL12RB1	-0.022	0.12	-10000	0	-0.82	4	4
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.09	0.21	-10000	0	-0.61	33	33
IL27/IL27R/JAK2/TYK2	-0.067	0.15	-10000	0	-0.56	10	10
positive regulation of T cell mediated cytotoxicity	-0.066	0.15	-10000	0	-0.55	10	10
STAT1 (dimer)	-0.12	0.24	0.52	16	-0.74	18	34
JAK2	0.011	0.054	-10000	0	-0.83	2	2
JAK1	0.014	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.055	0.14	-10000	0	-0.53	10	10
T cell proliferation	-0.16	0.24	-10000	0	-0.53	105	105
IL12/IL12R/TYK2/JAK2	-0.055	0.16	-10000	0	-0.68	14	14
IL17A	-0.063	0.15	-10000	0	-10000	0	0
mast cell activation	0.066	0.15	0.55	10	-10000	0	10
IFNG	-0.02	0.048	-10000	0	-0.13	66	66
T cell differentiation	-0.005	0.008	-10000	0	-0.022	60	60
STAT3 (dimer)	-0.055	0.14	-10000	0	-0.53	10	10
STAT5A (dimer)	-0.055	0.14	-10000	0	-0.53	10	10
STAT4 (dimer)	-0.075	0.16	-10000	0	-0.52	24	24
STAT4	-0.024	0.14	-10000	0	-0.46	39	39
T cell activation	-0.012	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.063	0.19	-10000	0	-0.68	8	8
GATA3	-0.043	0.34	-10000	0	-1.5	25	25
IL18	-0.025	0.11	-10000	0	-0.29	58	58
positive regulation of mast cell cytokine production	-0.055	0.14	-10000	0	-0.52	10	10
IL27/EBI3	-0.099	0.12	-10000	0	-0.44	6	6
IL27RA	0.004	0.027	-10000	0	-10000	0	0
IL6	-0.17	0.33	-10000	0	-0.82	97	97
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.041	0.18	-10000	0	-0.59	43	43
EBI3	-0.15	0.17	-10000	0	-0.32	237	237
TNF	-0.069	0.21	-10000	0	-0.6	64	64

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.041	0.1	-9999	-0.38	21	21
NFATC4	0	0.11	-9999	-0.5	3	3
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.045	0.13	-9999	-0.4	54	54
JUN	0.002	0.097	-9999	-0.28	12	12
HRAS	0.011	0.021	-9999	-0.32	2	2
DOCK7	-0.014	0.14	-9999	-0.38	57	57
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.055	0.15	-9999	-0.49	54	54
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.023	0.063	-9999	-0.36	2	2
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.024	0.15	-9999	-0.44	54	54
RAF1	-0.003	0.12	-9999	-0.4	21	21
ErbB2/ErbB3/neuregulin 2	-0.068	0.17	-9999	-0.51	64	64
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.022	0.082	-9999	-0.3	5	5
mol:PI-3-4-5-P3	0	0.002	-9999	-10000	0	0
cell proliferation	-0.13	0.33	-9999	-0.68	115	115
FOS	-0.11	0.28	-9999	-0.52	151	151
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.045	0.13	-9999	-0.4	54	54
MAPK3	-0.083	0.25	-9999	-0.5	111	111
MAPK1	-0.083	0.25	-9999	-0.5	111	111
JAK2	-0.014	0.14	-9999	-0.39	35	35
NF2	-0.002	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.015	0.13	-9999	-0.37	54	54
NRG1	-0.067	0.24	-9999	-0.8	47	47
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.014	0.13	-9999	-0.35	64	64
MAPK9	-0.022	0.061	-9999	-0.29	1	1
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.008	0.12	-9999	-0.73	12	12
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.003	0.01	-9999	-10000	0	0
STAT3 (dimer)	0	0.003	-9999	-10000	0	0
RNF41	0.027	0.007	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.032	0.086	-9999	-0.38	2	2
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.056	0.2	-9999	-0.39	94	94
myelination	0.009	0.11	-9999	-0.46	3	3
PPP3CB	-0.01	0.12	-9999	-0.35	54	54
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-9999	-0.65	2	2
NRG2	-0.081	0.26	-9999	-0.79	57	57
mol:GDP	-0.015	0.13	-9999	-0.37	54	54
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.005	0.13	-9999	-0.41	21	21
SRC	0.013	0.015	-9999	-0.31	1	1
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.013	0.13	-9999	-0.39	26	26
MAP2K1	-0.075	0.23	-9999	-0.53	44	44
heart morphogenesis	-0.045	0.13	-9999	-0.4	54	54
RAS family/GDP	-0.035	0.1	-9999	-0.36	21	21
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.009	-9999	-10000	0	0
CHRNE	0.01	0.035	-9999	-0.13	18	18
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.045	0.13	-9999	-0.4	54	54
CDC42	0.013	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.054	0.16	-9999	-0.54	40	40
MAP4K1	-0.019	0.12	-9999	-0.41	38	38
MAP3K8	0	0.1	-9999	-0.82	8	8
PRKCB	-0.027	0.13	-9999	-0.36	53	53
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.014	0.1	-9999	-0.55	5	5
JUN	-0.1	0.24	-9999	-0.51	121	121
MAP3K7	0.014	0.1	-9999	-0.55	5	5
GRAP2	-0.041	0.2	-9999	-0.77	34	34
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.02	0.11	-9999	-0.51	7	7
LAT	0.006	0.076	-9999	-0.72	5	5
LCP2	0.009	0.039	-9999	-0.31	7	7
MAPK8	-0.004	0.14	-9999	-0.74	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.006	0.11	-9999	-0.36	33	33
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.05	0.15	-9999	-0.51	40	40

×

LPA receptor mediated events

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
GNB1/GNG2	-0.045	0.15	-9999	-0.54	39	39
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.051	-9999	-0.6	1	1
AP1	-0.25	0.36	-9999	-0.68	175	175
mol:PIP3	-0.041	0.12	-9999	-0.42	42	42
AKT1	-0.027	0.095	-9999	-0.58	5	5
PTK2B	0	0.085	-9999	-0.27	40	40
RHOA	0.031	0.046	-9999	-10000	0	0
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.004	0.074	-9999	-0.32	1	1
MAGI3	0.012	0.037	-9999	-0.82	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.014	0.13	-9999	-0.44	39	39
HRAS/GDP	-0.001	0.014	-9999	-0.21	2	2
positive regulation of microtubule depolymerization	0.009	0.088	-9999	-0.36	9	9
NF kappa B1 p50/RelA	-0.044	0.12	-9999	-0.54	13	13
endothelial cell migration	-0.028	0.2	-9999	-0.64	41	41
ADCY4	-0.015	0.19	-9999	-0.61	40	40
ADCY5	-0.046	0.21	-9999	-0.64	43	43
ADCY6	-0.015	0.19	-9999	-0.62	39	39
ADCY7	-0.015	0.19	-9999	-0.62	39	39
ADCY1	-0.018	0.19	-9999	-0.62	40	40
ADCY2	-0.038	0.21	-9999	-0.66	41	41
ADCY3	-0.015	0.19	-9999	-0.61	40	40
ADCY8	-0.056	0.19	-9999	-0.65	40	40
ADCY9	-0.015	0.19	-9999	-0.62	39	39
GSK3B	0.008	0.081	-9999	-0.3	12	12
arachidonic acid secretion	-0.008	0.18	-9999	-0.57	39	39
GNG2	0.012	0.037	-9999	-0.81	1	1
TRIP6	0.026	0.008	-9999	-10000	0	0
GNAO1	-0.04	0.2	-9999	-0.6	53	53
HRAS	0.012	0.021	-9999	-0.31	2	2
NFKBIA	0.01	0.079	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.035	0.11	-9999	-0.97	6	6
JUN	-0.17	0.35	-9999	-0.82	110	110
LPA/LPA2/NHERF2	-0.001	0.007	-9999	-10000	0	0
TIAM1	-0.045	0.13	-9999	-1.2	6	6
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.003	0.075	-9999	-0.32	1	1
PLCB3	0.03	0.009	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
positive regulation of mitosis	-0.008	0.18	-9999	-0.57	39	39
LPA/LPA1-2-3	-0.05	0.15	-9999	-0.54	39	39
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	0.004	0.11	-9999	-0.35	39	39
GNAZ	-0.02	0.17	-9999	-0.57	41	41
EGFR/PI3K-beta/Gab1	-0.043	0.13	-9999	-0.44	42	42
positive regulation of dendritic cell cytokine production	-0.05	0.15	-9999	-0.53	39	39
LPA/LPA2/MAGI-3	-0.002	0.027	-9999	-0.59	1	1
ARHGEF1	-0.001	0.15	-9999	-0.49	39	39
GNAI2	-0.02	0.17	-9999	-0.57	41	41
GNAI3	-0.02	0.17	-9999	-0.57	41	41
GNAI1	-0.022	0.17	-9999	-0.56	42	42
LPA/LPA3	-0.01	0.044	-9999	-0.21	21	21
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.056	0.19	-9999	-0.65	41	41
HB-EGF/EGFR	-0.052	0.17	-9999	-0.54	44	44
HBEGF	-0.059	0.19	-9999	-0.62	42	42
mol:DAG	0.003	0.075	-9999	-0.32	1	1
cAMP biosynthetic process	-0.027	0.2	-9999	-0.56	53	53
NFKB1	0.012	0.038	-9999	-0.82	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.01	0.079	-9999	-10000	0	0
GNAQ	0.019	0.029	-9999	-10000	0	0
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.003	0.066	-9999	-0.31	21	21
LPAR1	-0.051	0.23	-9999	-0.83	39	39
IL8	-0.13	0.19	-9999	-0.48	58	58
PTK2	-0.01	0.15	-9999	-0.5	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.014	0.13	-9999	-0.45	39	39
EGFR	0.006	0.075	-9999	-0.82	4	4
PLCG1	-0.016	0.085	-9999	-0.29	14	14
PLD2	-0.01	0.15	-9999	-0.5	39	39
G12/G13	-0.044	0.15	-9999	-0.53	39	39
PI3K-beta	-0.032	0.11	-9999	-0.71	5	5
cell migration	-0.016	0.059	-9999	-0.25	11	11
SLC9A3R2	0.013	0	-9999	-10000	0	0
PXN	0.003	0.11	-9999	-0.36	39	39
HRAS/GTP	-0.009	0.19	-9999	-0.59	39	39
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.081	0.24	-9999	-0.57	79	79
PRKCE	0.005	0.084	-9999	-0.82	5	5
PRKCD	0.011	0.072	-9999	-10000	0	0
Gi(beta/gamma)	-0.008	0.18	-9999	-0.59	39	39
mol:LPA	0.003	0.019	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.03	0.13	-9999	-0.45	39	39
MAPKKK cascade	-0.008	0.18	-9999	-0.57	39	39
contractile ring contraction involved in cytokinesis	0.031	0.046	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.086	0.19	-9999	-0.43	114	114
GNA15	0.008	0.056	-9999	-0.35	2	2
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.008	0.09	-9999	-0.41	6	6
GNA11	0.01	0.069	-9999	-0.42	10	10
Rac1/GTP	-0.036	0.12	-9999	-1	6	6
MMP2	-0.028	0.2	-9999	-0.64	41	41

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.18	-9999	-0.46	60	60
IKBKB	-0.018	0.071	-9999	-0.36	3	3
AKT1	-0.04	0.1	-9999	-0.26	23	23
IKBKG	-0.016	0.074	-9999	-0.33	5	5
CALM1	-0.034	0.085	-9999	-0.35	2	2
PIK3CA	0.008	0.065	-9999	-0.82	3	3
MAP3K1	-0.071	0.18	-9999	-0.64	16	16
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.044	0.089	-9999	-0.38	2	2
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.081	0.13	-9999	-0.28	110	110
LYN	0.013	0	-9999	-10000	0	0
BLNK	0.013	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
BCR complex	-0.16	0.24	-9999	-0.52	136	136
CD22	-0.15	0.22	-9999	-0.51	103	103
CAMK2G	-0.024	0.081	-9999	-0.32	2	2
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.003	0.072	-9999	-0.31	25	25
SHC/GRB2/SOS1	-0.094	0.14	-9999	-10000	0	0
GO:0007205	-0.044	0.09	-9999	-0.38	2	2
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.034	0.086	-9999	-0.35	2	2
NFATC1	-0.068	0.16	-9999	-0.53	20	20
B-cell antigen/BCR complex	-0.16	0.24	-9999	-0.52	136	136
PAG1/CSK	-0.001	0.028	-9999	-0.63	1	1
NFKBIB	0.003	0.028	-9999	-0.11	3	3
HRAS	-0.036	0.098	-9999	-0.35	2	2
NFKBIA	0.003	0.027	-9999	-0.11	3	3
NF-kappa-B/RelA/I kappa B beta	0.009	0.024	-9999	-0.2	1	1
RasGAP/Csk	-0.14	0.2	-9999	-0.48	94	94
mol:GDP	-0.04	0.082	-9999	-0.36	2	2
PTEN	0.012	0.038	-9999	-0.82	1	1
CD79B	-0.029	0.11	-9999	-0.31	63	63
NF-kappa-B/RelA/I kappa B alpha	0.009	0.024	-9999	-0.2	1	1
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.084	0.18	-9999	-0.43	74	74
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.05	0.087	-9999	-0.38	2	2
CSK	0.013	0	-9999	-10000	0	0
FOS	-0.14	0.21	-9999	-0.47	130	130
CHUK	-0.016	0.074	-9999	-0.33	5	5
IBTK	0.013	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.066	0.093	-9999	-0.49	8	8
PTPN6	-0.14	0.2	-9999	-0.6	51	51
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.034	-9999	-0.13	18	18
VAV2	-0.13	0.18	-9999	-0.51	41	41
ubiquitin-dependent protein catabolic process	0.008	0.027	-9999	-0.11	3	3
BTK	-0.018	0.16	-9999	-1.2	8	8
CD19	-0.14	0.2	-9999	-0.45	97	97
MAP4K1	-0.019	0.12	-9999	-0.41	38	38
CD72	0.012	0.021	-9999	-0.31	2	2
PAG1	0.012	0.038	-9999	-0.82	1	1
MAPK14	-0.053	0.16	-9999	-0.52	16	16
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.034	0.088	-9999	-10000	0	0
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.059	0.17	-9999	-0.43	71	71
RAF1	-0.027	0.094	-9999	-0.32	2	2
RasGAP/p62DOK/SHIP	-0.14	0.19	-9999	-0.47	93	93
CD79A	-0.19	0.3	-9999	-0.52	184	184
re-entry into mitotic cell cycle	-0.08	0.13	-9999	-0.28	108	108
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.008	0.083	-9999	-10000	0	0
MAPK1	-0.008	0.083	-9999	-10000	0	0
CD72/SHP1	-0.099	0.21	-9999	-0.64	34	34
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.062	0.17	-9999	-0.52	25	25
actin cytoskeleton organization	-0.084	0.18	-9999	-0.68	11	11
NF-kappa-B/RelA	0.023	0.044	-9999	-0.2	1	1
Calcineurin	-0.035	0.058	-9999	-10000	0	0
PI3K	-0.13	0.16	-9999	-0.52	32	32
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.054	0.085	-9999	-0.34	2	2
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.1	0.24	-9999	-0.97	22	22
DAPP1	-0.13	0.26	-9999	-1.2	18	18
cytokine secretion	-0.063	0.15	-9999	-0.49	20	20
mol:DAG	-0.05	0.087	-9999	-0.38	2	2
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.017	0.089	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.16	0.23	-9999	-0.48	154	154
mol:PI-3-4-5-P3	-0.094	0.12	-9999	-0.36	29	29
ETS1	-0.015	0.076	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.11	0.17	-9999	-0.46	74	74
B-cell antigen/BCR complex/LYN	-0.12	0.2	-9999	-0.48	81	81
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.82	2	2
RAC1	-0.09	0.19	-9999	-0.74	11	11
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.55	81	81
CARD11	-0.073	0.12	-9999	-0.51	12	12
FCGR2B	-0.028	0.18	-9999	-0.74	27	27
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
IKK complex	0.001	0.035	-9999	-0.14	2	2
PTPRC	-0.031	0.17	-9999	-0.59	36	36
PDPK1	-0.042	0.1	-9999	-0.27	23	23
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.013	0	-9999	-10000	0	0
POU2F2	0.009	0.024	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.081	-9999	-0.71	6	6
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.57	15	15
PTK2	0.016	0.15	-9999	-0.54	16	16
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.025	0.1	-9999	-0.31	57	57
SRC	0.013	0.015	-9999	-0.31	1	1
CDKN1B	-0.063	0.18	-9999	-0.61	45	45
VEGFA	0.008	0.065	-9999	-0.82	3	3
ILK	-0.063	0.18	-9999	-0.61	45	45
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.058	0.16	-9999	-0.56	45	45
PTK2B	0.019	0.11	-9999	-0.5	21	21
alphaV/beta3 Integrin/JAM-A	-0.059	0.16	-9999	-0.47	59	59
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.019	0.1	-9999	-0.58	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.18	0.26	-9999	-0.53	159	159
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.003	0.11	-9999	-0.54	3	3
alphaV/beta3 Integrin/Syndecan-1	-0.019	0.1	-9999	-0.57	15	15
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.24	0.25	-9999	-0.61	118	118
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
alphaV/beta3 Integrin/Osteopontin	-0.07	0.16	-9999	-0.57	37	37
RPS6KB1	-0.21	0.24	-9999	-0.57	118	118
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.094	0.15	-9999	-0.74	15	15
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.094	0.15	-9999	-0.74	15	15
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.034	0.15	-9999	-0.61	27	27
cell adhesion	-0.029	0.098	-9999	-0.53	15	15
ANGPTL3	0.005	0.026	-9999	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.072	-9999	-0.62	6	6
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.008	0.065	-9999	-0.82	3	3
ITGB3	-0.01	0.14	-9999	-0.82	14	14
IGF1	-0.18	0.35	-9999	-0.82	113	113
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.1	-9999	-0.57	15	15
apoptosis	0.01	0.053	-9999	-0.81	2	2
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.018	0.1	-9999	-0.57	15	15
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.037	0.13	-9999	-0.61	22	22
CSF1	0	0.1	-9999	-0.82	8	8
PIK3C2A	-0.064	0.18	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.054	0.14	-9999	-0.77	3	3
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.023	0.11	-9999	-0.54	21	21
FAK1/Vinculin	0.024	0.12	-9999	-0.48	8	8
alphaV beta3/Integrin/ppsTEM5	-0.018	0.1	-9999	-0.57	15	15
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.068	0.24	-9999	-0.75	52	52
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	0.013	0	-9999	-10000	0	0
F11R	0.024	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	-0.036	0.11	-9999	-0.57	15	15
alphaV/beta3 Integrin/TGFBR2	-0.021	0.11	-9999	-0.6	17	17
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.01	0.076	-9999	-0.54	9	9
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.016	0.094	-9999	-0.53	15	15
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	354	354
alphaV/beta3 Integrin/Pyk2	-0.022	0.1	-9999	-0.5	21	21
SDC1	0.01	0.033	-9999	-0.31	5	5
VAV3	0.026	0.098	-9999	-0.52	14	14
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.087	0.27	-9999	-0.82	59	59
FAK1/Paxillin	0.024	0.12	-9999	-0.48	8	8
cell migration	0.034	0.12	-9999	-0.42	8	8
ITGAV	0.01	0.053	-9999	-0.82	2	2
PI3K	-0.055	0.15	-9999	-0.44	60	60
SPP1	-0.082	0.2	-9999	-0.42	109	109
KDR	0.007	0.075	-9999	-0.82	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.053	-9999	-0.82	2	2
COL4A3	-0.012	0.14	-9999	-0.82	15	15
angiogenesis	-0.083	0.18	-9999	-0.59	36	36
Rac1/GTP	-0.014	0.083	-9999	-0.47	14	14
EDIL3	-0.023	0.14	-9999	-0.82	9	9
cell proliferation	-0.021	0.11	-9999	-0.59	17	17

×

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	0.009	0.23	-10000	0	-0.97	22	22
NCK1/PAK1/Dok-R	-0.029	0.093	-10000	0	-0.43	23	23
NCK1/Dok-R	-0.071	0.25	-10000	0	-1.2	22	22
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
mol:beta2-estradiol	-0.003	0.049	0.25	16	-10000	0	16
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.014	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.01	0.071	0.25	14	-0.33	12	26
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.062	0.23	-10000	0	-1.1	22	22
FN1	-0.22	0.15	-10000	0	-0.31	354	354
PLD2	-0.003	0.28	-10000	0	-1.3	22	22
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GRB14	-0.007	0.13	-10000	0	-0.82	12	12
ELK1	0.013	0.25	-10000	0	-1.1	22	22
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.25	-10000	0	-1.2	22	22
CDKN1A	-0.011	0.18	-10000	0	-0.65	21	21
ITGA5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.071	0.25	-10000	0	-1.2	22	22
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.025	0.17	-10000	0	-0.69	22	22
PLG	-0.013	0.28	-10000	0	-1.3	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.007	0.22	-10000	0	-0.93	22	22
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
ANGPT2	-0.11	0.22	-10000	0	-0.74	23	23
BMX	-0.018	0.3	-10000	0	-1.3	23	23
ANGPT1	-0.041	0.3	-10000	0	-1.5	19	19
tube development	-0.018	0.19	-10000	0	-0.74	22	22
ANGPT4	-0.058	0.23	-10000	0	-0.75	46	46
response to hypoxia	0	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.02	0.3	-10000	0	-1.3	22	22
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.021	0.21	-10000	0	-0.85	22	22
mol:L-citrulline	0.025	0.17	-10000	0	-0.69	22	22
AGTR1	-0.32	0.41	-10000	0	-0.81	196	196
MAPK14	-0.014	0.28	-10000	0	-1.2	22	22
Tie2/SHP2	-0.028	0.16	-10000	0	-1.4	6	6
TEK	0.012	0.19	-10000	0	-1.5	6	6
RPS6KB1	0.008	0.22	-10000	0	-0.93	22	22
Angiotensin II/AT1	-0.24	0.32	-10000	0	-0.63	195	195
Tie2/Ang1/GRB2	-0.008	0.3	-10000	0	-1.3	22	22
MAPK3	0.008	0.26	-10000	0	-1.1	22	22
MAPK1	0.008	0.26	-10000	0	-1.1	22	22
Tie2/Ang1/GRB7	-0.032	0.3	-10000	0	-1.3	22	22
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MAPK8	-0.012	0.3	-10000	0	-1.3	23	23
PI3K	-0.007	0.26	-10000	0	-1.1	22	22
FES	-0.014	0.28	-10000	0	-1.2	22	22
Crk/Dok-R	-0.071	0.25	-10000	0	-1.2	22	22
Tie2/Ang1/ABIN2	-0.008	0.3	-10000	0	-1.3	22	22
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.014	0.2	-10000	0	-0.85	22	22
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.008	0.22	-10000	0	-0.93	22	22
Tie2/Ang2	-0.041	0.25	-10000	0	-1	22	22
Tie2/Ang1	-0.016	0.31	-10000	0	-1.4	22	22
FOXO1	0.02	0.2	-10000	0	-0.86	22	22
ELF1	0.015	0.078	-10000	0	-0.84	4	4
ELF2	-0.007	0.28	-10000	0	-1.2	22	22
mol:Choline	0	0.27	-10000	0	-1.2	22	22
cell migration	-0.024	0.057	-10000	0	-0.24	22	22
FYN	-0.024	0.21	-10000	0	-0.85	22	22
DOK2	0.001	0.076	-10000	0	-0.38	16	16
negative regulation of cell cycle	-0.008	0.16	-10000	0	-0.58	22	22
ETS1	0.015	0.046	-10000	0	-10000	0	0
PXN	0.022	0.18	-10000	0	-0.75	22	22
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.022	0.19	-10000	0	-0.8	22	22
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.089	0.28	-10000	0	-0.77	65	65
MAPKKK cascade	0	0.27	-10000	0	-1.2	22	22
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.012	0.3	-10000	0	-1.3	22	22
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.028	0.16	-10000	0	-0.61	22	22
mol:Phosphatidic acid	0	0.27	-10000	0	-1.2	22	22
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.025	0.17	-10000	0	-0.69	22	22
Rac1/GTP	-0.053	0.18	-10000	0	-0.86	22	22
MMP2	-0.01	0.29	-10000	0	-1.3	22	22

×

Signaling events mediated by PTP1B

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
PDGFRB	0.012	0.038	-10000	0	-0.82	1	1
Jak2/Leptin Receptor	-0.023	0.097	0.21	4	-0.39	18	22
PTP1B/AKT1	-0.002	0.063	-10000	0	-0.32	3	3
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.011	0.069	-10000	0	-0.32	5	5
EGFR	0.005	0.076	-10000	0	-0.83	4	4
EGF/EGFR	-0.083	0.18	-10000	0	-0.5	74	74
CSF1	0	0.1	-10000	0	-0.82	8	8
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.014	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.098	0.12	-10000	0	-0.45	20	20
Insulin Receptor/Insulin	-0.012	0.04	-10000	0	-10000	0	0
HCK	-0.007	0.08	-10000	0	-0.31	31	31
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.002	0.066	-10000	0	-0.31	4	4
EGF	-0.11	0.29	-10000	0	-0.78	76	76
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.017	0.099	-10000	0	-0.39	5	5
TXN	0.011	0.016	-10000	0	-0.32	1	1
PTP1B/IRS1/GRB2	-0.055	0.17	-10000	0	-0.49	60	60
cell migration	0.011	0.069	0.32	5	-10000	0	5
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.044	0.19	-10000	0	-0.6	45	45
ITGA2B	-0.072	0.25	-10000	0	-0.82	50	50
CSF1R	0.009	0.048	-10000	0	-0.41	5	5
Prolactin Receptor/Prolactin	-0.039	0.15	-10000	0	-0.64	26	26
FGR	0.011	0.029	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.003	0.065	-10000	0	-0.34	3	3
Crk/p130 Cas	0.001	0.06	-10000	0	-0.38	1	1
DOK1	0.007	0.062	-10000	0	-0.32	2	2
JAK2	-0.012	0.092	-10000	0	-0.4	14	14
Jak2/Leptin Receptor/Leptin	-0.055	0.14	-10000	0	-0.57	29	29
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.011	0.07	-10000	0	-0.32	5	5
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.19	0.2	-10000	0	-0.34	275	275
SRC	0.012	0.029	-10000	0	-10000	0	0
ITGB3	-0.012	0.14	-10000	0	-0.82	14	14
CAT1/PTP1B	-0.088	0.15	-10000	0	-0.38	60	60
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.015	0.052	-10000	0	-0.57	3	3
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.054	0.14	-10000	0	-0.61	28	28
negative regulation of transcription	-0.011	0.092	-10000	0	-0.39	14	14
FCGR2A	-0.006	0.082	-10000	0	-0.33	27	27
FER	0.007	0.066	-10000	0	-0.82	3	3
alphaIIb/beta3 Integrin	-0.08	0.22	-10000	0	-0.67	59	59
BLK	-0.24	0.37	-10000	0	-0.75	165	165
Insulin Receptor/Insulin/Shc	0	0.001	-10000	0	-10000	0	0
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	0.004	0.086	-10000	0	-0.67	7	7
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.12	0.19	-10000	0	-0.5	50	50
PRL	0.001	0.016	-10000	0	-0.31	1	1
SOCS3	-0.07	0.34	-10000	0	-1.5	27	27
SPRY2	0.009	0.056	-10000	0	-0.65	3	3
Insulin Receptor/Insulin/IRS1	-0.067	0.18	-10000	0	-0.55	59	59
CSF1/CSF1R	-0.008	0.094	-10000	0	-0.51	10	10
Ras protein signal transduction	0.02	0.023	-10000	0	-10000	0	0
IRS1	-0.087	0.27	-10000	0	-0.82	59	59
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.008	0.067	-10000	0	-0.31	22	22
STAT5B	-0.007	0.07	-10000	0	-0.27	10	10
STAT5A	-0.007	0.07	-10000	0	-0.27	10	10
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.068	-10000	0	-0.36	4	4
CSN2	-0.007	0.055	-10000	0	-10000	0	0
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
LAT	0.002	0.065	-10000	0	-0.54	5	5
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.01	0.11	-10000	0	-0.43	26	26
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.13	0.16	-10000	0	-0.31	213	213

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.015	-9999	-0.31	1	1
LAT2	-0.018	0.1	-9999	-0.37	6	6
AP1	-0.2	0.28	-9999	-0.61	135	135
mol:PIP3	-0.016	0.15	-9999	-0.42	39	39
IKBKB	0.003	0.092	-9999	-0.27	20	20
AKT1	-0.017	0.14	-9999	-0.58	6	6
IKBKG	0.003	0.092	-9999	-0.26	21	21
MS4A2	-0.066	0.14	-9999	-0.31	114	114
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
MAP3K1	0.01	0.1	-9999	-0.46	7	7
mol:Ca2+	-0.008	0.12	-9999	-0.31	39	39
LYN	0.01	0.007	-9999	-10000	0	0
CBLB	-0.01	0.089	-9999	-0.38	2	2
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.081	0.18	-9999	-0.5	79	79
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.072	-9999	-0.31	25	25
PLD2	-0.048	0.15	-9999	-0.44	42	42
PTPN13	-0.002	0.1	-9999	-0.55	6	6
PTPN11	0.011	0.039	-9999	-0.85	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.018	0.1	-9999	-0.37	4	4
SYK	0.01	0.007	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.062	0.13	-9999	-0.42	39	39
LAT	-0.014	0.1	-9999	-0.43	8	8
PAK2	0.002	0.11	-9999	-0.51	8	8
NFATC2	-0.15	0.28	-9999	-0.75	85	85
HRAS	-0.008	0.12	-9999	-0.51	10	10
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.03	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.099	0.17	-9999	-0.46	69	69
Antigen/IgE/Fc epsilon R1	-0.09	0.15	-9999	-0.43	69	69
mol:GDP	-0.016	0.13	-9999	-0.5	15	15
JUN	-0.17	0.35	-9999	-0.82	110	110
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.044	0.079	-9999	-0.34	6	6
CHUK	0.003	0.092	-9999	-0.27	20	20
KLRG1	-0.022	0.11	-9999	-0.41	14	14
VAV1	-0.022	0.11	-9999	-0.48	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.01	0.089	-9999	-0.35	4	4
negative regulation of mast cell degranulation	-0.02	0.1	-9999	-0.39	12	12
BTK	-0.047	0.11	-9999	-0.58	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.048	0.18	-9999	-0.5	48	48
GAB2/PI3K/SHP2	-0.065	0.13	-9999	-0.44	37	37
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.019	0.094	-9999	-0.29	35	35
RAF1	0.018	0.02	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.2	-9999	-0.57	57	57
FCER1G	-0.008	0.082	-9999	-0.32	31	31
FCER1A	-0.076	0.23	-9999	-0.55	76	76
Antigen/IgE/Fc epsilon R1/Fyn	-0.081	0.14	-9999	-0.47	42	42
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.005	0.11	-9999	-0.66	11	11
DUSP1	-0.12	0.31	-9999	-0.82	79	79
NF-kappa-B/RelA	-0.019	0.044	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.004	0.083	-9999	-0.37	1	1
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.042	0.1	-9999	-0.55	10	10
FER	-0.013	0.098	-9999	-0.43	7	7
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.072	0.17	-9999	-0.53	60	60
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.012	0.13	-9999	-0.55	11	11
cytokine secretion	-0.014	0.032	-9999	-0.22	1	1
SPHK1	-0.014	0.092	-9999	-0.37	5	5
PTK2	-0.005	0.085	-9999	-0.39	1	1
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.065	0.13	-9999	-0.43	46	46
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.01	0.14	-9999	-0.4	39	39
MAP2K2	0.025	0.018	-9999	-10000	0	0
MAP2K1	0.025	0.018	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.047	0.093	-9999	-0.42	13	13
MAP2K4	0.021	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.2	-9999	-0.61	54	54
mol:Choline	-0.048	0.14	-9999	-0.43	42	42
SHC/Grb2/SOS1	-0.031	0.066	-9999	-0.39	1	1
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.003	0.081	-9999	-10000	0	0
HCLS1	-0.012	0.093	-9999	-0.38	5	5
PRKCB	-0.01	0.12	-9999	-0.33	41	41
FCGR2B	-0.028	0.18	-9999	-0.74	27	27
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.02	0.11	-9999	-0.4	12	12
LCP2	0.009	0.039	-9999	-0.32	7	7
PLA2G4A	-0.041	0.16	-9999	-0.51	35	35
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.048	0.14	-9999	-0.43	42	42
IKK complex	0.018	0.075	-9999	-0.22	8	8
WIPF1	0.013	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.032	0.043	-9999	-0.92	1	1
VEGFR1 homodimer/NRP1	-0.002	0.042	-9999	-0.93	1	1
mol:DAG	-0.011	0.16	-9999	-0.49	49	49
VEGFR1 homodimer/NRP1/VEGFR 121	-0.005	0.067	-9999	-0.77	3	3
CaM/Ca2+	-0.003	0.15	-9999	-0.45	49	49
HIF1A	0.021	0.018	-9999	-0.38	1	1
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.01	0.16	-9999	-0.9	3	3
PLCG1	-0.011	0.16	-9999	-0.49	49	49
NOS3	0.018	0.15	-9999	-0.43	49	49
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.019	0.15	-9999	-0.41	49	49
FLT1	0.031	0.048	-9999	-1	1	1
PGF	-0.069	0.25	-9999	-0.81	49	49
VEGFR1 homodimer/NRP2/VEGFR121	-0.015	0.074	-9999	-0.76	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
eNOS/Hsp90	0.025	0.14	-9999	-0.8	1	1
endothelial cell proliferation	-0.028	0.19	-9999	-0.52	50	50
mol:Ca2+	-0.011	0.16	-9999	-0.48	49	49
MAPK3	-0.015	0.18	-9999	-0.43	70	70
MAPK1	-0.015	0.18	-9999	-0.43	70	70
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.069	0.25	-9999	-0.8	49	49
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.009	0.13	-9999	-0.82	13	13
VEGFA homodimer	0.008	0.065	-9999	-0.82	3	3
VEGFR1 homodimer/VEGFA homodimer	0.029	0.074	-9999	-0.82	3	3
platelet activating factor biosynthetic process	-0.007	0.17	-9999	-0.95	2	2
PI3K	-0.049	0.15	-9999	-0.47	51	51
PRKCA	-0.024	0.18	-9999	-0.46	70	70
PRKCB	-0.021	0.16	-9999	-0.47	53	53
VEGFR1 homodimer/PLGF homodimer	-0.024	0.17	-9999	-0.54	49	49
VEGFA	0.008	0.065	-9999	-0.82	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.011	0.16	-9999	-0.49	49	49
RASA1	0.041	0.04	-9999	-0.85	1	1
NRP2	-0.013	0.089	-9999	-0.31	39	39
VEGFR1 homodimer	0.031	0.048	-9999	-1	1	1
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.014	0.16	-9999	-0.8	4	4
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:PI-3-4-5-P3	-0.048	0.14	-9999	-0.46	51	51
mol:L-citrulline	0.019	0.15	-9999	-0.41	49	49
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.004	0.063	-9999	-0.72	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.005	0.067	-9999	-0.76	3	3
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.046	0.14	-9999	-0.44	51	51
PDPK1	0.001	0.16	-9999	-0.45	51	51
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.005	0.083	-9999	-0.89	3	3
mol:NADP	0.019	0.15	-9999	-0.41	49	49
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.004	0.062	-9999	-0.7	3	3
VEGFR1 homodimer/NRP2	0.018	0.066	-9999	-0.92	1	1

×

Aurora C 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0.053	-9999	-0.82	2	2
Aurora C/Aurora B/INCENP	-0.039	0.077	-9999	-0.38	8	8
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.011	0.02	-9999	-10000	0	0
AURKB	-0.06	0.14	-9999	-0.31	109	109
AURKC	-0.001	0.066	-9999	-0.31	21	21

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.015	-10000	0	-10000	0	0
HSPA8	0.004	0.075	-10000	0	-0.82	4	4
SMAD3/SMAD4/ER alpha	-0.051	0.14	-10000	0	-0.59	23	23
AKT1	0.008	0.01	-10000	0	-10000	0	0
GSC	-0.2	0.55	-10000	0	-1.5	70	70
NKX2-5	0.002	0.029	-10000	0	-0.31	4	4
muscle cell differentiation	0.025	0.05	0.44	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.005	0.079	-10000	0	-10000	0	0
SMAD4	-0.011	0.059	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.078	-10000	0	-0.54	5	5
SMAD3/SMAD4/VDR	0.01	0.044	-10000	0	-10000	0	0
MYC	0.001	0.14	-10000	0	-0.82	13	13
CDKN2B	-0.075	0.14	-10000	0	-10000	0	0
AP1	-0.25	0.5	-10000	0	-1	132	132
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.055	-10000	0	-0.71	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.002	0.062	-10000	0	-10000	0	0
SP3	0.016	0.002	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.012	0.074	-10000	0	-0.31	22	22
SMAD3/SMAD4/GR	-0.017	0.044	-10000	0	-10000	0	0
GATA3	-0.031	0.18	-10000	0	-0.77	27	27
SKI/SIN3/HDAC complex/NCoR1	0.041	0.029	-10000	0	-10000	0	0
MEF2C/TIF2	-0.047	0.17	-10000	0	-0.5	48	48
endothelial cell migration	-0.009	0.1	1.4	1	-10000	0	1
MAX	0.013	0.006	-10000	0	-10000	0	0
RBBP7	0.012	0.004	-10000	0	-10000	0	0
RBBP4	0.007	0.065	-10000	0	-0.82	3	3
RUNX2	-0.076	0.15	-10000	0	-0.32	131	131
RUNX3	-0.007	0.12	-10000	0	-0.6	16	16
RUNX1	-0.13	0.16	-10000	0	-0.31	215	215
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.006	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-0.31	1	1
CDKN1A	0.024	0.071	-10000	0	-10000	0	0
KAT2B	0.016	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.037	0.094	-10000	0	-0.44	3	3
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.012	0.004	-10000	0	-10000	0	0
SERPINE1	0.009	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.041	0.12	-10000	0	-0.59	21	21
SMAD3/SMAD4/ATF3	-0.15	0.26	-10000	0	-0.62	113	113
SAP30	0.01	0.038	-10000	0	-0.82	1	1
Cbp/p300/PIAS3	0.033	0.045	-10000	0	-10000	0	0
JUN	-0.25	0.5	-10000	0	-1	123	123
SMAD3/SMAD4/IRF7	-0.016	0.045	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.002	0.091	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.066	0.095	0.46	4	-10000	0	4
DLX1	-0.031	0.19	-10000	0	-0.82	26	26
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.22	0.39	-10000	0	-0.88	128	128
SMAD3/SMAD4/Max	-0.017	0.044	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.006	0.041	-10000	0	-0.54	2	2
ZBTB17	0.021	0.011	-10000	0	-10000	0	0
LAMC1	0.026	0.053	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.017	0.043	-10000	0	-10000	0	0
IRF7	0.014	0.016	-10000	0	-0.31	1	1
ESR1	-0.048	0.19	-10000	0	-0.53	55	55
HNF4A	-0.003	0.045	-10000	0	-0.31	10	10
MEF2C	0.004	0.098	-10000	0	-0.7	2	2
SMAD2-3/SMAD4	-0.031	0.055	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.024	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.016	0.024	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.017	0.01	-10000	0	-10000	0	0
SKIL	0.012	0.038	-10000	0	-0.82	1	1
HDAC1	0.012	0.004	-10000	0	-10000	0	0
HDAC2	0.012	0.004	-10000	0	-10000	0	0
SNIP1	0.008	0.053	-10000	0	-0.82	2	2
GCN5L2	0.006	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.011	0.045	-10000	0	-10000	0	0
MSG1/HSC70	-0.18	0.1	-10000	0	-0.68	9	9
SMAD2	-0.002	0.04	-10000	0	-10000	0	0
SMAD3	-0.005	0.047	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.075	-10000	0	-0.44	5	5
SMAD2/SMAD2/SMAD4	0.014	0.027	-10000	0	-10000	0	0
NCOR1	0.012	0.004	-10000	0	-10000	0	0
NCOA2	-0.067	0.24	-10000	0	-0.82	47	47
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.018	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.014	0.076	-10000	0	-10000	0	0
IFNB1	0.014	0.057	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.006	0.099	-10000	0	-1	1	1
CITED1	-0.26	0.14	-10000	0	-0.32	404	404
SMAD2-3/SMAD4/ARC105	-0.022	0.046	-10000	0	-10000	0	0
RBL1	-0.007	0.13	-10000	0	-0.82	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.006	0.081	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.081	0.11	-10000	0	-0.49	14	14
SMAD7	-0.1	0.28	-10000	0	-0.6	92	92
MYC/MIZ-1	0.013	0.11	-10000	0	-0.63	13	13
SMAD3/SMAD4	0.063	0.1	0.31	44	-0.35	1	45
IL10	-0.026	0.19	-10000	0	-0.61	38	38
PIASy/HDAC complex	0.007	0.01	-10000	0	-10000	0	0
PIAS3	0.016	0.005	-10000	0	-10000	0	0
CDK2	0.018	0.011	-10000	0	-10000	0	0
IL5	-0.016	0.14	-10000	0	-0.5	25	25
CDK4	0.019	0.012	-10000	0	-10000	0	0
PIAS4	0.007	0.01	-10000	0	-10000	0	0
ATF3	-0.18	0.35	-10000	0	-0.79	120	120
SMAD3/SMAD4/SP1	-0.015	0.054	-10000	0	-10000	0	0
FOXG1	-0.003	0.071	-10000	0	-0.39	13	13
FOXO3	0.017	0.015	-10000	0	-10000	0	0
FOXO1	0.017	0.015	-10000	0	-10000	0	0
FOXO4	0.017	0.015	-10000	0	-10000	0	0
heart looping	0.004	0.097	-10000	0	-0.68	2	2
CEBPB	0.009	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.048	0.14	-10000	0	-0.6	26	26
MYOD1	-0.002	0.029	-10000	0	-0.31	4	4
SMAD3/SMAD4/HNF4	-0.023	0.052	-10000	0	-0.4	1	1
SMAD3/SMAD4/GATA3	-0.051	0.14	-10000	0	-0.54	29	29
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.037	-10000	0	-0.82	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.075	0.11	-10000	0	-0.54	11	11
SMAD3/SMAD4/SP1-3	0.007	0.056	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.015	0.021	-10000	0	-10000	0	0
SIN3B	0.012	0.004	-10000	0	-10000	0	0
SIN3A	0.012	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.017	0.095	-10000	0	-0.52	2	2
ITGB5	0.036	0.059	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.042	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.26	0.29	-10000	0	-0.59	205	205
AR	-0.34	0.41	-10000	0	-0.82	205	205
negative regulation of cell growth	-0.039	0.13	-10000	0	-0.55	4	4
SMAD3/SMAD4/MYOD	-0.023	0.049	-10000	0	-10000	0	0
E2F5	0.012	0.038	-10000	0	-0.82	1	1
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.011	0.067	-10000	0	-0.36	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.066	-10000	0	-10000	0	0
TFDP1	0.012	0.038	-10000	0	-0.82	1	1
SMAD3/SMAD4/AP1	-0.27	0.51	-10000	0	-1.1	123	123
SMAD3/SMAD4/RUNX2	-0.066	0.095	-10000	0	-0.46	4	4
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.022	0.17	-10000	0	-0.82	21	21

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.038	-9999	-0.82	1	1
alphaV beta3 Integrin	-0.02	0.12	-9999	-0.66	15	15
PTK2	-0.04	0.15	-9999	-0.6	29	29
positive regulation of JNK cascade	-0.021	0.081	-9999	-0.34	29	29
CDC42/GDP	0.03	0.13	-9999	-0.47	29	29
Rac1/GDP	0.032	0.12	-9999	-0.46	29	29
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.026	0.1	-9999	-0.42	29	29
nectin-3/I-afadin	-0.037	0.15	-9999	-0.63	29	29
RAPGEF1	0.023	0.14	-9999	-0.53	29	29
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0.16	-9999	-0.62	29	29
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.82	1	1
TLN1	0.019	0.075	-9999	-0.93	1	1
Rap1/GTP	-0.022	0.087	-9999	-0.36	29	29
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.037	0.15	-9999	-0.63	29	29
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.024	0.16	-9999	-0.58	29	29
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
PI3K	-0.031	0.12	-9999	-0.5	30	30
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.006	0.034	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.022	0.085	-9999	-0.36	29	29
PVRL1	0.004	0.055	-9999	-0.31	14	14
PVRL3	-0.036	0.2	-9999	-0.82	29	29
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
CLDN1	-0.26	0.15	-9999	-0.33	398	398
JAM-A/CLDN1	-0.14	0.14	-9999	-0.57	39	39
SRC	-0.043	0.17	-9999	-0.71	29	29
ITGB3	-0.01	0.14	-9999	-0.82	14	14
nectin-1(dimer)/I-afadin/I-afadin	-0.006	0.034	-9999	-10000	0	0
FARP2	0.018	0.15	-9999	-0.57	29	29
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.032	0.13	-9999	-0.54	29	29
nectin-1/I-afadin	-0.006	0.034	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.037	0.13	-9999	-0.55	29	29
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.021	0.081	-9999	-0.34	29	29
alphaV/beta3 Integrin/Talin	0.018	0.13	-9999	-0.59	15	15
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0.011	0.08	-9999	-0.99	1	1
VAV2	0.017	0.15	-9999	-0.59	29	29
RAP1/GDP	-0.026	0.1	-9999	-0.43	29	29
ITGAV	0.01	0.053	-9999	-0.82	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.032	0.13	-9999	-0.54	29	29
nectin-3(dimer)/I-afadin/I-afadin	-0.037	0.15	-9999	-0.63	29	29
Rac1/GTP	-0.027	0.1	-9999	-0.44	29	29
PTPRM	-0.019	0.082	-9999	-0.32	29	29
E-cadherin/beta catenin/alpha catenin	-0.003	0.017	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.017	0.085	-9999	-0.47	16	16
RGS9BP	-0.034	0.19	-9999	-0.82	28	28
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.066	0.24	-9999	-0.81	47	47
mol:Na +	-0.021	0.057	-9999	-10000	0	0
mol:ADP	-0.044	0.19	-9999	-0.63	46	46
GNAT2	0.009	0.021	-9999	-0.31	2	2
RGS9-1/Gbeta5/R9AP	-0.089	0.2	-9999	-0.55	78	78
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.011	-9999	-10000	0	0
GRK7	0.007	0.007	-9999	-10000	0	0
CNGB3	0.003	0.005	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.014	0.063	-9999	-10000	0	0
Cone PDE6	-0.077	0.18	-9999	-0.48	78	78
Cone Metarhodopsin II	-0.048	0.15	-9999	-0.51	46	46
Na + (4 Units)	-0.025	0.057	-9999	-10000	0	0
GNAT2/GDP	-0.077	0.18	-9999	-0.48	78	78
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.015	-9999	-10000	0	0
Cone Transducin	-0.018	0.09	-9999	-0.5	16	16
SLC24A2	-0.01	0.065	-9999	-0.31	21	21
GNB3/GNGT2	-0.022	0.11	-9999	-0.63	16	16
GNB3	-0.013	0.14	-9999	-0.78	16	16
GNAT2/GTP	-0.001	0.014	-9999	-10000	0	0
CNGA3	-0.027	0.11	-9999	-0.31	60	60
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.057	-9999	-10000	0	0
mol:Pi	-0.089	0.2	-9999	-0.55	78	78
Cone CNG Channel	-0.016	0.043	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.065	-9999	-0.31	21	21
RGS9	-0.076	0.26	-9999	-0.82	52	52
PDE6C	0.003	0.016	-9999	-0.31	1	1
GNGT2	0.01	0.045	-9999	-0.44	4	4
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.004	0.006	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.003	0.04	-9999	-0.63	2	2
Necdin/E2F1	-0.067	0.12	-9999	-0.75	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.036	0.1	-9999	-0.48	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.28	-9999	-0.57	231	231
NT-4/5 (dimer)/p75(NTR)	-0.074	0.18	-9999	-0.66	35	35
IKBKB	0.013	0	-9999	-10000	0	0
AKT1	-0.004	0.12	-9999	-0.48	23	23
IKBKG	0.013	0	-9999	-10000	0	0
BDNF	-0.013	0.14	-9999	-0.6	21	21
MGDIs/NGR/p75(NTR)/LINGO1	-0.049	0.12	-9999	-0.56	18	18
FURIN	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.057	0.14	-9999	-0.56	29	29
LINGO1	-0.003	0.072	-9999	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.025	-9999	-10000	0	0
proBDNF (dimer)	-0.013	0.14	-9999	-0.6	21	21
NTRK1	-0.003	0.063	-9999	-0.31	19	19
RTN4R	0.013	0	-9999	-10000	0	0
neuron apoptosis	-0.01	0.13	-9999	-0.49	24	24
IRAK1	0.013	0	-9999	-10000	0	0
SHC1	-0.021	0.13	-9999	-0.56	20	20
ARHGDIA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.04	0.11	-9999	-0.51	20	20
MAGEH1	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.045	0.12	-9999	-0.51	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-9999	-0.49	25	25
proNGF (dimer)	0.006	0.069	-9999	-0.56	6	6
MAGED1	0.013	0	-9999	-10000	0	0
APP	0.013	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.021	0.15	-9999	-0.62	26	26
ZNF274	0.013	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.037	0.1	-9999	-0.48	20	20
NGF	0.006	0.07	-9999	-0.56	6	6
cell cycle arrest	0.042	0.16	-9999	-0.47	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.009	0.086	-9999	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.064	0.16	-9999	-0.59	36	36
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.046	0.12	-9999	-0.56	21	21
PSENEN	0.013	0	-9999	-10000	0	0
mol:ceramide	-0.01	0.12	-9999	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.07	-9999	-0.43	2	2
p75(NTR)/beta APP	-0.05	0.13	-9999	-0.63	18	18
BEX1	-0.35	0.41	-9999	-0.82	216	216
mol:GDP	-0.031	0.13	-9999	-0.57	20	20
NGF (dimer)	-0.096	0.13	-9999	-0.5	30	30
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.043	0.11	-9999	-0.52	18	18
PIK3R1	0.013	0	-9999	-10000	0	0
RAC1/GTP	-0.039	0.11	-9999	-0.5	20	20
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.046	0.12	-9999	-0.56	21	21
RHOB	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.061	0.093	-9999	-10000	0	0
NT3 (dimer)	-0.05	0.2	-9999	-0.6	50	50
TP53	-0.005	0.13	-9999	-0.45	31	31
PRDM4	-0.01	0.12	-9999	-0.51	20	20
BDNF (dimer)	-0.13	0.16	-9999	-0.54	40	40
PIK3CA	0.008	0.065	-9999	-0.82	3	3
SORT1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.035	0.1	-9999	-0.48	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.042	0.12	-9999	-0.52	22	22
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	0.023	0.12	-9999	-0.6	4	4
DIABLO	0.013	0	-9999	-10000	0	0
SMPD2	-0.01	0.12	-9999	-0.51	20	20
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.045	0.12	-9999	-0.56	20	20
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-9999	-0.63	1	1
NT3 (dimer)/p75(NTR)	-0.095	0.2	-9999	-0.66	46	46
MAPK8	0.017	0.13	-9999	-0.66	4	4
MAPK9	0.024	0.12	-9999	-0.6	3	3
APAF1	0.012	0.038	-9999	-0.82	1	1
NTF3	-0.05	0.2	-9999	-0.6	50	50
NTF4	-0.021	0.15	-9999	-0.62	26	26
NDN	0.005	0.084	-9999	-0.82	5	5
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.033	0.095	-9999	-0.44	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.054	-9999	-0.65	3	3
RhoA-B-C/GTP	-0.046	0.12	-9999	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.048	0.12	-9999	-0.48	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.052	0.13	-9999	-0.51	31	31
PRKACB	0.012	0.038	-9999	-0.82	1	1
proBDNF (dimer)/p75 ECD	-0.022	0.11	-9999	-0.63	14	14
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.036	0.19	-9999	-0.67	35	35
BIRC2	0.013	0	-9999	-10000	0	0
neuron projection morphogenesis	0.066	0.17	-9999	-0.47	20	20
BAD	0.029	0.12	-9999	-0.59	4	4
RIPK2	0.013	0	-9999	-10000	0	0
NGFR	-0.061	0.18	-9999	-0.42	84	84
CYCS	-0.001	0.11	-9999	-0.48	20	20
ADAM17	0.01	0.053	-9999	-0.82	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.042	0.12	-9999	-0.52	22	22
BCL2L11	0.029	0.12	-9999	-0.59	4	4
BDNF (dimer)/p75(NTR)	-0.069	0.16	-9999	-0.63	31	31
PI3K	-0.042	0.12	-9999	-0.52	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.04	0.11	-9999	-0.51	20	20
NDNL2	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.055	0.14	-9999	-0.65	20	20
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.04	0.11	-9999	-0.51	20	20
TRAF6	0.01	0.053	-9999	-0.82	2	2
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
PLG	-0.004	0.04	-9999	-0.31	8	8
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.017	0.14	-9999	-0.49	31	31
SQSTM1	0.013	0	-9999	-10000	0	0
NGFRAP1	0.013	0	-9999	-10000	0	0
CASP3	0.03	0.11	-9999	-0.53	4	4
E2F1	-0.086	0.15	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.013	0.059	-9999	-0.53	3	3
NGF (dimer)/TRKA	-0.013	0.064	-9999	-0.63	3	3
MMP7	-0.18	0.22	-9999	-0.37	246	246
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-9999	-0.49	22	22
MMP3	-0.04	0.11	-9999	-0.31	69	69
APAF-1/Caspase 9	-0.04	0.11	-9999	-0.6	7	7

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.03	0.068	-9999	-0.32	8	8
IRAK/TOLLIP	0.029	0.004	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.24	-9999	-0.67	74	74
IL1A	-0.054	0.22	-9999	-0.78	41	41
IL1B	-0.032	0.18	-9999	-0.63	40	40
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-0.42	2	2
IL1R2	-0.082	0.24	-9999	-0.58	78	78
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.071	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.005	0.084	-9999	-0.82	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.066	0.027	-9999	-10000	0	0
JUN	-0.073	0.22	-9999	-0.43	122	122
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.066	0.13	-9999	-0.47	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.072	0.14	-9999	-0.51	38	38
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.066	0.13	-9999	-0.47	38	38
IL1 beta fragment/IL1R1/IL1RAP	-0.076	0.15	-9999	-0.53	39	39
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.019	0.12	-9999	-0.52	19	19
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.045	0.11	-9999	-0.63	11	11
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.053	-9999	-0.82	2	2
PI3K	-0.004	0.049	-9999	-0.63	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.001	0.087	-9999	-0.34	8	8
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.076	0.15	-9999	-0.53	39	39
IL1 beta/IL1R2	-0.1	0.22	-9999	-0.6	75	75
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.028	-9999	-0.44	2	2
NF kappa B1 p50/RelA	-0.057	0.12	-9999	-0.55	8	8
IRAK3	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.068	0.14	-9999	-0.48	44	44
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.1	-9999	-0.34	38	38
IL1 alpha/IL1R1/IL1RAP	-0.083	0.15	-9999	-0.56	38	38
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.022	0.035	-9999	-0.47	2	2
IL1RAP	-0.07	0.14	-9999	-0.31	124	124
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.053	0.12	-9999	-0.49	12	12
CASP1	0.008	0.059	-9999	-0.52	5	5
IL1RN/IL1R2	-0.11	0.21	-9999	-0.62	61	61
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.069	0.14	-9999	-0.5	39	39
TMEM189-UBE2V1	0.004	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.081	-9999	-0.34	4	4
PIK3CA	0.008	0.065	-9999	-0.82	3	3
IL1RN	-0.056	0.16	-9999	-0.38	86	86
TRAF6/TAK1/TAB1/TAB2	-0.002	0.029	-9999	-0.46	2	2
MAP2K6	0.021	0.076	-9999	-0.44	13	13

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.065	0.082	-10000	0	-0.33	23	23
NT3 (dimer)/TRKC	-0.09	0.19	-10000	0	-0.67	40	40
NT3 (dimer)/TRKB	-0.085	0.18	-10000	0	-0.57	50	50
SHC/Grb2/SOS1/GAB1/PI3K	0.037	0.029	-10000	0	-0.33	3	3
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.013	0.14	-10000	0	-0.6	21	21
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.003	0.063	-10000	0	-0.31	19	19
NTRK2	0.005	0.084	-10000	0	-0.82	5	5
NTRK3	-0.055	0.17	-10000	0	-0.39	83	83
NT-4/5 (dimer)/TRKB	-0.067	0.16	-10000	0	-0.58	39	39
neuron apoptosis	0.039	0.091	0.42	15	-10000	0	15
SHC 2-3/Grb2	-0.042	0.099	-10000	0	-0.46	15	15
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.029	0.092	-10000	0	-0.63	6	6
SHC3	-0.046	0.1	-10000	0	-0.55	12	12
STAT3 (dimer)	0.018	0.025	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.087	0.17	-10000	0	-0.58	45	45
RIN/GDP	-0.009	0.062	-10000	0	-0.27	3	3
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.032	0.091	-10000	0	-0.44	18	18
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.025	0.045	-10000	0	-10000	0	0
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.021	0.15	-10000	0	-0.62	26	26
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.019	0.078	-10000	0	-0.54	8	8
TRKA/NEDD4-2	-0.008	0.039	-10000	0	-10000	0	0
ELMO1	-0.31	0.4	-10000	0	-0.82	190	190
RhoG/GTP/ELMO1/DOCK1	-0.22	0.27	-10000	0	-0.56	191	191
NGF	0.006	0.07	-10000	0	-0.56	6	6
HRAS	0.012	0.021	-10000	0	-0.31	2	2
DOCK1	0.007	0.075	-10000	0	-0.82	4	4
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.015	0.15	-10000	0	-0.79	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.2	0.23	-10000	0	-0.47	205	205
mol:GDP	-0.016	0.089	-10000	0	-0.38	5	5
NGF (dimer)	0.006	0.069	-10000	0	-0.56	6	6
RhoG/GDP	-0.25	0.31	-10000	0	-0.64	190	190
RIT1/GDP	-0.004	0.063	-10000	0	-0.28	2	2
TIAM1	-0.17	0.16	-10000	0	-0.32	277	277
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.021	0.11	-10000	0	-0.6	15	15
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.024	-10000	0	-0.54	1	1
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.05	0.2	-10000	0	-0.6	50	50
RAP1/GDP	-0.018	0.042	-10000	0	-0.25	1	1
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.013	0.14	-10000	0	-0.6	21	21
ubiquitin-dependent protein catabolic process	-0.01	0.053	-10000	0	-0.54	3	3
Schwann cell development	-0.042	0.032	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.042	0.017	-10000	0	-0.32	1	1
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.066	0.15	-10000	0	-0.66	13	13
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.036	-10000	0	-10000	0	0
STAT3	0.018	0.025	-10000	0	-10000	0	0
axon guidance	-0.064	0.14	-10000	0	-0.62	13	13
MAPK3	0.015	0.077	-10000	0	-0.49	8	8
MAPK1	0.015	0.077	-10000	0	-0.49	8	8
CDC42/GDP	-0.004	0.063	-10000	0	-0.28	2	2
NTF3	-0.05	0.2	-10000	0	-0.6	50	50
NTF4	-0.021	0.15	-10000	0	-0.62	26	26
NGF (dimer)/TRKA/FAIM	-0.01	0.053	-10000	0	-0.54	3	3
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.13	0.11	-10000	0	-0.47	26	26
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.053	0.18	-10000	0	-0.58	40	40
RGS19	0.013	0	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.047	-10000	0	-0.42	1	1
Rac1/GDP	-0.004	0.063	-10000	0	-0.26	3	3
NGF (dimer)/TRKA/GRIT	-0.011	0.055	-10000	0	-0.55	3	3
neuron projection morphogenesis	0	0.094	-10000	0	-0.52	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.01	0.053	-10000	0	-0.54	3	3
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.061	0.18	-10000	0	-0.42	84	84
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.076	-10000	0	-0.35	18	18
RAS family/GTP/PI3K	0.03	0.032	-10000	0	-0.36	3	3
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.021	-10000	0	-0.46	1	1
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.056	-10000	0	-0.61	3	3
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.008	0.039	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.019	0.1	-10000	0	-0.55	15	15
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.008	0.043	-10000	0	-0.46	3	3
MATK	-0.001	0.093	-10000	0	-0.51	13	13
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.015	0.041	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.036	0.098	-10000	0	-0.44	23	23
Rac1/GTP	-0.19	0.14	-10000	0	-0.35	194	194
FRS2 family/SHP2/CRK family	-0.001	0.021	-10000	0	-0.46	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.049	0.35	-9999	-0.92	14	14
PLK1	0.044	0.068	-9999	-10000	0	0
BIRC5	0.024	0.12	-9999	-1.5	1	1
HSPA1B	0.049	0.35	-9999	-0.92	14	14
MAP2K1	0.032	0.037	-9999	-10000	0	0
BRCA2	0.044	0.36	-9999	-0.98	17	17
FOXM1	0.038	0.39	-9999	-1	17	17
XRCC1	0.049	0.35	-9999	-0.92	14	14
FOXM1B/p19	-0.095	0.31	-9999	-0.91	25	25
Cyclin D1/CDK4	0.036	0.33	-9999	-0.88	11	11
CDC2	0.042	0.36	-9999	-0.94	16	16
TGFA	0.02	0.34	-9999	-0.92	9	9
SKP2	0.042	0.36	-9999	-0.98	17	17
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.049	0.35	-9999	-0.92	14	14
RB1	-0.053	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.034	0.36	-9999	-1	17	17
AURKB	-0.005	0.12	-9999	-10000	0	0
CENPF	0.043	0.36	-9999	-0.95	14	14
CDK4	0.019	0.015	-9999	-10000	0	0
MYC	0.041	0.35	-9999	-0.92	21	21
CHEK2	0.032	0.037	-9999	-10000	0	0
ONECUT1	0.033	0.34	-9999	-0.91	14	14
CDKN2A	-0.13	0.16	-9999	-0.31	205	205
LAMA4	0.049	0.35	-9999	-0.92	14	14
FOXM1B/HNF6	0.026	0.37	-9999	-1	14	14
FOS	-0.18	0.66	-9999	-1.2	129	129
SP1	0.014	0.005	-9999	-10000	0	0
CDC25B	0.048	0.35	-9999	-0.92	14	14
response to radiation	0.015	0.034	-9999	-10000	0	0
CENPB	0.049	0.35	-9999	-0.92	14	14
CENPA	0.036	0.37	-9999	-0.97	18	18
NEK2	0.039	0.36	-9999	-0.96	14	14
HIST1H2BA	0.04	0.35	-9999	-0.92	14	14
CCNA2	0.01	0.047	-9999	-0.33	9	9
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.037	0.37	-9999	-1	14	14
CCNB2	0.046	0.35	-9999	-0.95	14	14
CCNB1	0.045	0.36	-9999	-0.96	14	14
ETV5	0.048	0.35	-9999	-0.92	14	14
ESR1	0	0.43	-9999	-1.1	34	34
CCND1	0.039	0.34	-9999	-0.89	13	13
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.05	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.12	0.23	-9999	-0.89	20	20
GAS1	-0.12	0.61	-9999	-1.2	104	104
MMP2	0.039	0.38	-9999	-1.1	17	17
RB1/FOXM1C	0.047	0.34	-9999	-0.92	14	14
CREBBP	0.013	0	-9999	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.012	0.093	-10000	0	-0.45	1	1
epithelial cell differentiation	-0.047	0.1	-10000	0	-0.48	10	10
ITCH	0.024	0.02	-10000	0	-10000	0	0
WWP1	0	0.079	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.007	0.075	-10000	0	-0.82	4	4
PRL	0.001	0.015	-10000	0	-0.31	1	1
neuron projection morphogenesis	0.005	0.14	-10000	0	-0.51	10	10
PTPRZ1	-0.015	0.13	-10000	0	-0.55	23	23
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.057	0.13	-10000	0	-0.56	11	11
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.042	0.17	-10000	0	-0.53	46	46
ADAM17	0.02	0.057	-10000	0	-0.81	2	2
ErbB4/ErbB4	-0.01	0.1	-10000	0	-0.52	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.044	0.17	-10000	0	-0.55	37	37
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.066	0.15	-10000	0	-0.49	46	46
GRIN2B	-0.028	0.15	-10000	0	-0.46	46	46
ErbB4/ErbB2/betacellulin	-0.039	0.12	-10000	0	-0.61	16	16
STAT1	0.006	0.048	-10000	0	-0.31	11	11
HBEGF	-0.004	0.073	-10000	0	-0.31	26	26
PRLR	-0.044	0.19	-10000	0	-0.6	46	46
E4ICDs/ETO2	-0.005	0.09	-10000	0	-0.57	2	2
axon guidance	0	0.086	-10000	0	-0.43	3	3
NEDD4	0.02	0.056	-10000	0	-0.8	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.043	0.15	-10000	0	-0.64	26	26
CBFA2T3	0.011	0.04	-10000	0	-0.56	2	2
ErbB4/ErbB2/HBEGF	-0.029	0.061	-10000	0	-0.57	2	2
MAPK3	-0.004	0.14	-10000	0	-0.52	11	11
STAT1 (dimer)	-0.007	0.089	-10000	0	-0.35	5	5
MAPK1	-0.004	0.14	-10000	0	-0.52	11	11
JAK2	0.01	0.053	-10000	0	-0.82	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.066	0.15	-10000	0	-0.49	46	46
NRG1	-0.034	0.2	-10000	0	-0.64	46	46
NRG3	-0.048	0.22	-10000	0	-0.82	36	36
NRG2	-0.081	0.26	-10000	0	-0.79	57	57
NRG4	0.009	0.033	-10000	0	-0.31	5	5
heart development	0	0.086	-10000	0	-0.43	3	3
neural crest cell migration	-0.032	0.16	-10000	0	-0.49	46	46
ERBB2	0.028	0.043	-10000	0	-0.61	2	2
WWOX/E4ICDs	-0.004	0.092	-10000	0	-0.94	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.036	0.083	-10000	0	-0.65	4	4
apoptosis	0.056	0.14	0.46	37	-10000	0	37
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.065	0.19	-10000	0	-0.55	55	55
ErbB4/ErbB2/epiregulin	-0.078	0.087	-10000	0	-0.55	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.021	0.14	-10000	0	-0.64	17	17
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.061	0.12	-10000	0	-0.47	28	28
MDM2	0.001	0.087	-10000	0	-0.45	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.061	0.15	-10000	0	-0.5	46	46
STAT5A	0.008	0.081	-10000	0	-0.51	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.07	0.16	-10000	0	-0.51	49	49
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.032	0.063	-10000	0	-0.42	1	1
STAT5A (dimer)	-0.05	0.11	-10000	0	-0.52	10	10
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.079	-10000	0	-0.51	1	1
LRIG1	0	0.1	-10000	0	-0.82	8	8
EREG	-0.14	0.16	-10000	0	-0.31	228	228
BTC	-0.014	0.15	-10000	0	-0.82	16	16
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0	0.086	-10000	0	-0.44	3	3
ERBB4	-0.01	0.1	-10000	0	-0.52	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.01	0.02	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.025	0.056	-10000	0	-0.5	2	2
glial cell differentiation	0.032	0.062	0.42	1	-10000	0	1
WWOX	0.012	0.038	-10000	0	-0.82	1	1
cell proliferation	-0.024	0.17	-10000	0	-0.54	21	21

×

Syndecan-3-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.04	0.12	-9999	-0.42	46	46
Syndecan-3/Neurocan	-0.035	0.12	-9999	-0.46	35	35
POMC	-0.16	0.33	-9999	-0.8	102	102
EGFR	0.007	0.075	-9999	-0.82	4	4
Syndecan-3/EGFR	-0.004	0.042	-9999	-0.46	4	4
AGRP	-0.005	0.064	-9999	-0.31	20	20
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.013	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.05	0.22	-9999	-0.76	39	39
long-term memory	0	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.039	0.08	-9999	-0.46	10	10
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0	0.009	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	-0.001	0.008	-9999	-10000	0	0
MC4R	0.001	0.038	-9999	-0.31	7	7
SRC	0.013	0.015	-9999	-0.31	1	1
PTN	-0.066	0.24	-9999	-0.81	47	47
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	-0.068	0.15	-9999	-0.41	80	80
Syndecan-3/AgRP	-0.006	0.025	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.007	0.027	-9999	-10000	0	0
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.038	0.079	-9999	-0.45	10	10
IL8	-0.081	0.17	-9999	-0.35	125	125
Syndecan-3/Fyn/Cortactin	0	0.005	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.13	0.25	-9999	-0.63	99	99
Gamma Secretase	0	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	-0.24	0.38	-10000	0	-0.82	151	151
HRAS	0.012	0.021	-10000	0	-0.31	2	2
EGFR	0.007	0.075	-10000	0	-0.82	4	4
AKT	0.019	0.025	-10000	0	-10000	0	0
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.11	0.16	-10000	0	-0.31	179	179
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.01	0.13	-10000	0	-0.69	16	16
PIK3R3	0.012	0.038	-10000	0	-0.82	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.059	0.098	-10000	0	-0.26	42	42
ERBB2	0.013	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.024	0.024	0.19	1	-0.17	1	2
PI3K	-0.039	0.095	0.23	1	-0.22	49	50
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.025	0.027	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.06	0.16	-10000	0	-0.47	62	62
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.056	-10000	0	-0.21	34	34
GNB1/GNG2	-0.001	0.025	-10000	0	-0.55	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.064	0.17	-10000	0	-0.52	61	61
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	0.014	0.038	0.12	61	-10000	0	61
GNAL	-0.09	0.27	-10000	0	-0.82	61	61
GNG2	0.012	0.038	-10000	0	-0.82	1	1
CRH	-0.015	0.082	-10000	0	-0.31	34	34
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.069	-10000	0	-0.46	11	11
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0	0.078	-9999	-10000	0	0
STMN1	-0.021	0.094	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.027	0.11	-9999	-0.33	27	27
Chromosomal passenger complex/Cul3 protein complex	0.006	0.071	-9999	-0.28	14	14
BIRC5	-0.018	0.1	-9999	-0.33	44	44
DES	-0.38	0.3	-9999	-0.61	296	296
Aurora C/Aurora B/INCENP	-0.016	0.088	-9999	-0.4	7	7
Aurora B/TACC1	-0.022	0.081	-9999	-0.71	1	1
Aurora B/PP2A	-0.026	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.005	0.026	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.048	0.15	-9999	-0.39	58	58
Cul3 protein complex	-0.018	0.087	-9999	-0.54	12	12
KIF2C	0	0.042	-9999	-10000	0	0
PEBP1	0.011	0.005	-9999	-10000	0	0
KIF20A	-0.04	0.12	-9999	-0.31	80	80
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.026	0.091	-9999	-10000	0	0
SEPT1	0.008	0.041	-9999	-0.31	8	8
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.007	0.045	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
H3F3B	-0.007	0.055	-9999	-10000	0	0
AURKB	-0.051	0.14	-9999	-0.31	109	109
AURKC	-0.001	0.066	-9999	-0.31	21	21
CDCA8	0.01	0.027	-9999	-0.33	3	3
cytokinesis	-0.066	0.083	-9999	-0.43	5	5
Aurora B/Septin1	-0.027	0.1	-9999	-0.46	5	5
AURKA	0.012	0.002	-9999	-10000	0	0
INCENP	0.009	0.054	-9999	-0.83	2	2
KLHL13	-0.017	0.14	-9999	-0.54	27	27
BUB1	-0.1	0.16	-9999	-0.32	170	170
hSgo1/Aurora B/Survivin	-0.028	0.12	-9999	-0.44	18	18
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.031	0.073	-9999	-10000	0	0
SGOL1	0.001	0.062	-9999	-0.31	18	18
CENPA	-0.007	0.069	-9999	-0.26	3	3
NCAPG	-0.018	0.096	-9999	-0.31	47	47
Aurora B/HC8 Proteasome	-0.026	0.091	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.026	0.091	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.035	0.12	-9999	-0.31	72	72
NPM1	-0.012	0.048	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.013	0	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.026	0.091	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.035	0.081	-9999	-0.39	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.048	-9999	-10000	0	0
MYLK	-0.008	0.06	-9999	-0.55	1	1
KIF23	-0.005	0.075	-9999	-0.32	26	26
VIM	-0.021	0.093	-9999	-10000	0	0
RACGAP1	0.013	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.048	-9999	-10000	0	0
Chromosomal passenger complex	-0.013	0.083	-9999	-0.27	12	12
Chromosomal passenger complex/EVI5	0.009	0.12	-9999	-0.48	6	6
TACC1	0.012	0.038	-9999	-0.82	1	1
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

LPA4-mediated signaling events

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
ADCY4	0.015	0.057	-9999	-0.55	5	5
ADCY5	-0.058	0.2	-9999	-0.55	66	66
ADCY6	0.015	0.057	-9999	-0.55	5	5
ADCY7	0.015	0.057	-9999	-0.55	5	5
ADCY1	0.007	0.091	-9999	-0.62	9	9
ADCY2	-0.041	0.17	-9999	-0.56	47	47
ADCY3	0.015	0.057	-9999	-0.55	5	5
ADCY8	-0.12	0.1	-9999	-0.7	5	5
PRKCE	0.005	0.065	-9999	-0.64	5	5
ADCY9	0.015	0.057	-9999	-0.55	5	5
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.057	0.11	-9999	-0.38	32	32

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.019	0.12	-10000	0	-0.78	12	12
HDAC1	0.002	0.009	-10000	0	-10000	0	0
AES	0.012	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.001	0.099	-10000	0	-0.82	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.008	0.065	-10000	0	-0.82	3	3
AP1	-0.14	0.26	-10000	0	-0.52	140	140
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.007	0.13	-10000	0	-0.82	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.054	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.018	0.11	-10000	0	-0.73	12	12
WIF1	-0.033	0.1	-10000	0	-0.31	59	59
NOTCH1	-0.019	0.12	-10000	0	-0.76	12	12
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.01	0.083	-10000	0	-0.31	34	34
DKK1	-0.041	0.12	-10000	0	-0.32	79	79
beta catenin/beta TrCP1	0.036	0.037	-10000	0	-10000	0	0
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	0	0.037	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.024	0.037	-10000	0	-0.35	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.2	0.36	-10000	0	-0.82	128	128
JUN	-0.17	0.35	-10000	0	-0.82	110	110
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.029	0.04	0.24	13	-10000	0	13
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.11	-10000	0	-0.55	19	19
HNF1A	0.012	0.002	-10000	0	-10000	0	0
CTBP1	0.012	0.002	-10000	0	-10000	0	0
MYC	-0.015	0.25	-10000	0	-1.5	13	13
NKD1	-0.014	0.14	-10000	0	-0.7	18	18
FZD1	0.013	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.024	0.12	-10000	0	-0.62	19	19
apoptosis	-0.14	0.26	-10000	0	-0.52	140	140
Delta 1/NOTCHprecursor	-0.019	0.12	-10000	0	-0.76	12	12
DLL1	0.011	0.04	-10000	0	-0.56	2	2
PPARD	0.024	0.017	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.061	-10000	0	-1.1	1	1
DVL1	0.003	0.01	-10000	0	-10000	0	0
CSNK2A1	0.014	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.037	0.078	-10000	0	-0.37	8	8
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.015	0.008	-10000	0	-10000	0	0
CCND1	0.018	0.044	-10000	0	-10000	0	0
WNT1	0.009	0.026	-10000	0	-0.31	3	3
Axin1/APC/beta catenin	0.042	0.052	-10000	0	-0.67	1	1
DKK2	-0.025	0.16	-10000	0	-0.66	28	28
NOTCH1 precursor/DVL1	-0.013	0.1	-10000	0	-0.64	12	12
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.025	0.13	-10000	0	-0.64	19	19
PPP2R5D	0.011	0.063	0.37	14	-10000	0	14
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.017	0.044	-10000	0	-10000	0	0
RBPJ	0.013	0.015	-10000	0	-0.31	1	1
CREBBP	0.017	0.004	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.012	0	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.001	0.013	-9999	-10000	0	0
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.015	0.063	-9999	-0.23	9	9
RAB3GAP2/RIMS1/UNC13B	-0.001	0.01	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.01	0.021	-9999	-0.31	2	2
mol:ACh	-0.007	0.04	-9999	-0.15	29	29
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.044	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.015	0.063	-9999	-0.23	9	9
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.018	0.093	-9999	-0.31	44	44
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.11	0.16	-9999	-0.4	61	61
SNAP25	-0.031	0.096	-9999	-0.38	29	29
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.16	0.22	-9999	-0.38	216	216
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.044	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.013	0.12	-9999	-0.44	29	29
CCNA2	0.007	0.044	-9999	-0.31	9	9
PIK3CA	0.009	0.065	-9999	-0.82	3	3
JAK3	-0.069	0.14	-9999	-0.31	124	124
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.018	0.14	-9999	-0.56	18	18
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.04	0.24	-9999	-0.97	29	29
IL2RB	-0.014	0.13	-9999	-0.5	27	27
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.046	0.19	-9999	-0.54	53	53
G1/S transition of mitotic cell cycle	0.039	0.054	-9999	-0.59	3	3
PTPN11	0.012	0.038	-9999	-0.82	1	1
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.009	0.11	-9999	-0.43	26	26
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.005	0.006	-9999	-10000	0	0
CDK6	0.008	0.065	-9999	-0.82	3	3
CCND3	0.028	0.13	-9999	-0.64	7	7

×

Insulin Pathway

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
CBL/APS/CAP	-0.055	0.15	-9999	-0.44	61	61
TC10/GTP	-0.004	0.038	-9999	-0.42	4	4
Insulin Receptor/Insulin/IRS1/Shp2	-0.062	0.17	-9999	-0.52	59	59
HRAS	0.012	0.021	-9999	-0.31	2	2
APS homodimer	0.013	0.015	-9999	-0.31	1	1
GRB14	-0.007	0.13	-9999	-0.82	12	12
FOXO3	-0.025	0.11	-9999	-0.72	11	11
AKT1	-0.011	0.16	-9999	-0.88	2	2
INSR	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.007	0.075	-9999	-0.82	4	4
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.038	0	-9999	-10000	0	0
CAV1	-0.046	0.18	-9999	-0.48	72	72
CBL/APS/CAP/Crk-II/C3G	-0.004	0.042	-9999	-0.46	4	4
Insulin Receptor/Insulin/IRS1/NCK2	-0.061	0.17	-9999	-0.51	59	59
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.056	0.15	-9999	-0.45	61	61
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.003	0.1	-9999	-10000	0	0
RPS6KB1	-0.001	0.15	-9999	-0.76	2	2
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.054	0.13	-9999	-0.78	2	2
HRAS/GTP	-0.05	0.13	-9999	-0.38	59	59
Insulin Receptor	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.057	0.15	-9999	-0.47	59	59
PRKCI	-0.014	0.034	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.063	0.16	-9999	-0.42	73	73
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.057	0.15	-9999	-0.46	61	61
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
AKT2	-0.011	0.16	-9999	-0.88	2	2
PRKCZ	-0.014	0.034	-9999	-10000	0	0
SH2B2	0.013	0.015	-9999	-0.31	1	1
SHC/SHIP	-0.03	0.16	-9999	-0.45	59	59
F2RL2	-0.08	0.16	-9999	-0.32	134	134
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.004	0.045	-9999	-0.49	4	4
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.04	0.17	-9999	-0.48	59	59
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.027	0.15	-9999	-1	11	11
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.087	0.27	-9999	-0.82	59	59
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.04	0.16	-9999	-0.48	59	59
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.002	0.15	-9999	-0.63	4	4
PTPRA	0.015	0	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0.053	-9999	-0.82	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.008	0.12	-9999	-0.33	59	59
Insulin Receptor/Insulin/IRS1	-0.062	0.17	-9999	-0.52	59	59
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.036	0.064	-9999	-0.47	3	3

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.002	0.079	-10000	0	-0.36	8	8
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.012	0.038	-10000	0	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.041	0.078	0.26	2	-10000	0	2
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.068	0.23	-10000	0	-0.63	69	69
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.024	-10000	0	-0.54	1	1
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.03	0.11	-10000	0	-0.31	63	63
PRKCI	0.013	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.039	0.1	-10000	0	-10000	0	0
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	0.042	0.082	0.26	2	-10000	0	2
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.027	0	-10000	0	-10000	0	0
SFN	-0.21	0.18	-10000	0	-0.33	314	314
LNPEP	-0.017	0.16	-10000	0	-0.82	18	18
YWHAE	0.013	0	-10000	0	-10000	0	0

×

IFN-gamma 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.027	0.16	-9999	-0.43	65	65
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.049	0.12	-9999	-0.74	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.011	0.043	-9999	-0.59	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.023	0.06	-9999	-0.3	2	2
CaM/Ca2+	-0.056	0.14	-9999	-0.4	65	65
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.02	0.16	-9999	-0.4	65	65
AKT1	-0.002	0.15	-9999	-0.62	3	3
MAP2K1	-0.005	0.15	-9999	-0.51	5	5
MAP3K11	-0.017	0.16	-9999	-0.4	65	65
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.066	-9999	-0.63	1	1
Rap1/GTP	-0.041	0.1	-9999	-0.6	1	1
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.063	0.15	-9999	-0.45	64	64
CEBPB	0.018	0.17	-9999	-0.82	5	5
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.059	0.15	-9999	-1.1	2	2
STAT1	-0.019	0.16	-9999	-0.4	65	65
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.1	0.28	-9999	-0.71	78	78
PIK3CA	0.008	0.065	-9999	-0.82	3	3
STAT1 (dimer)/PIAS1	-0.01	0.15	-9999	-0.47	5	5
CEBPB/PTGES2/Cbp/p300	-0.035	0.081	-9999	-0.44	5	5
mol:Ca2+	-0.06	0.15	-9999	-0.43	65	65
MAPK3	0.01	0.14	-9999	-0.52	5	5
STAT1 (dimer)	-0.03	0.08	-9999	-0.42	2	2
MAPK1	0.01	0.14	-9999	-0.52	5	5
JAK2	0.006	0.056	-9999	-0.84	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.009	0.014	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.017	0.18	-9999	-0.66	23	23
SMAD7	0.041	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.05	0.12	-9999	-0.76	1	1
PI3K	-0.056	0.14	-9999	-0.51	8	8
IFNG	-0.1	0.28	-9999	-0.72	78	78
apoptosis	0.013	0.13	-9999	-0.45	23	23
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.004	0.067	-9999	-0.31	22	22
CAMK2B	0.005	0.084	-9999	-0.82	5	5
FRAP1	0	0.14	-9999	-0.56	3	3
PRKCD	-0.002	0.15	-9999	-0.63	3	3
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.023	0.06	-9999	-0.3	2	2
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
IRF1	0.029	0.12	-9999	-0.53	1	1
STAT1 (dimer)/PIASy	-0.054	0.13	-9999	-0.48	5	5
SOCS1	0.001	0.074	-9999	-1.5	1	1
mol:GDP	-0.048	0.12	-9999	-0.71	1	1
CASP1	0.039	0.062	-9999	-0.35	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.042	0.057	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.055	0.13	-9999	-0.48	9	9
RAP1/GDP	-0.041	0.1	-9999	-0.6	1	1
CBL	-0.017	0.16	-9999	-0.4	65	65
MAP3K1	-0.016	0.16	-9999	-0.4	64	64
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.023	0.06	-9999	-0.3	2	2
PTPN11	-0.027	0.16	-9999	-0.43	65	65
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.16	0.34	-9999	-0.82	101	101
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.026	-9999	-0.31	3	3
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.023	-9999	-10000	0	0
HIF1A	0.022	0.024	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.004	0.04	-9999	-0.5	3	3
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.13	0.16	-9999	-0.31	210	210
ARNT/IPAS	-0.13	0.25	-9999	-0.63	101	101
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.023	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.023	-9999	-10000	0	0
PHD1-3/OS9	-0.018	0.087	-9999	-0.53	12	12
HIF1A/RACK1/Elongin B/Elongin C	-0.003	0.017	-9999	-10000	0	0
VHL	0.008	0.065	-9999	-0.82	3	3
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.023	-9999	-10000	0	0
EGLN3	-0.017	0.14	-9999	-0.51	28	28
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.01	0.053	-9999	-0.82	2	2
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.051	-9999	-0.6	3	3
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.073	-9999	-0.29	1	1

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0.001	0.099	-9999	-0.82	7	7
CDKN1A	-0.012	0.088	-9999	-10000	0	0
PRL-3/alpha Tubulin	-0.017	0.056	-9999	-10000	0	0
mol:Ca2+	-0.013	0.1	-9999	-0.64	9	9
AGT	-0.019	0.13	-9999	-0.44	35	35
CCNA2	-0.061	0.2	-9999	-0.58	4	4
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.11	0.26	-9999	-0.62	104	104
CDK2/Cyclin E1	0.004	0.076	-9999	-10000	0	0
MAPK3	0.005	0.063	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.005	0.063	-9999	-10000	0	0
PTP4A1	-0.071	0.21	-9999	-0.48	104	104
PTP4A3	-0.014	0.091	-9999	-0.31	41	41
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.005	0.063	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1	-0.016	0.092	-9999	-0.25	15	15
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.067	0.2	-9999	-0.58	4	4
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.012	0.041	-9999	-10000	0	0
RHOC	-0.016	0.092	-9999	-10000	0	0
RHOA	-0.016	0.092	-9999	-10000	0	0
cell motility	-0.015	0.098	-9999	-0.26	15	15
PRL-1/alpha Tubulin	-0.06	0.2	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.026	0.096	-9999	-0.67	7	7
ROCK1	-0.015	0.099	-9999	-0.26	15	15
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.07	0.21	-9999	-0.48	104	104
ATF5	0	0.065	-9999	-0.31	20	20

×

Class IB PI3K non-lipid kinase events

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

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

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

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0	-10000	0	-10000	0	0
MAP4K4	-0.003	0.14	-10000	0	-0.7	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
PKC zeta/ceramide	-0.018	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.67	35	35
BAX	-0.006	0.02	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.023	0.008	-10000	0	-10000	0	0
BAD	-0.017	0.04	-10000	0	-10000	0	0
SMPD1	-0.006	0.096	-10000	0	-0.26	58	58
RB1	-0.018	0.046	-10000	0	-0.5	1	1
FADD/Caspase 8	0.009	0.14	-10000	0	-0.66	11	11
MAP2K4	-0.009	0.038	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.011	0.05	-10000	0	-0.51	2	2
EGF	-0.11	0.29	-10000	0	-0.78	76	76
mol:ceramide	-0.028	0.043	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.023	0.029	-10000	0	-0.63	1	1
ASAH1	0.012	0.038	-10000	0	-0.82	1	1
negative regulation of cell cycle	-0.019	0.045	-10000	0	-0.49	1	1
cell proliferation	-0.099	0.16	-10000	0	-0.39	114	114
BID	-0.017	0.092	-10000	0	-0.38	13	13
MAP3K1	-0.017	0.04	-10000	0	-10000	0	0
EIF2A	0	0.037	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.002	0.047	-10000	0	-0.47	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.002	0.047	-10000	0	-0.47	2	2
Cathepsin D/ceramide	-0.018	0.041	-10000	0	-10000	0	0
FADD	-0.003	0.14	-10000	0	-0.7	11	11
KSR1	-0.019	0.053	-10000	0	-0.55	2	2
MAPK8	-0.01	0.06	-10000	0	-0.32	11	11
PRKRA	-0.017	0.04	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.18	0.35	-10000	0	-0.82	113	113
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.042	-10000	0	-10000	0	0
CTSD	0.013	0.015	-10000	0	-0.31	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.028	-10000	0	-0.62	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.086	0.19	-10000	0	-0.42	114	114
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.023	0.029	-10000	0	-0.63	1	1
RelA/NF kappa B1	-0.001	0.028	-10000	0	-0.63	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.012	0.15	-10000	0	-0.74	11	11
TNFR1A/BAG4/TNF-alpha	-0.067	0.18	-10000	0	-0.54	59	59
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.002	0.048	-10000	0	-0.48	2	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	0.004	0.052	0.18	27	-10000	0	27
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
TNFR1A/BAG4	-0.001	0.028	-10000	0	-0.63	1	1
EIF2AK2	-0.009	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.066	0.18	-10000	0	-0.54	58	58
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.079	-10000	0	-10000	0	0
MAP2K2	-0.002	0.048	-10000	0	-0.48	2	2
SMPD3	-0.011	0.12	-10000	0	-0.3	63	63
TNF	-0.09	0.27	-10000	0	-0.77	64	64
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.023	0.11	0.28	70	-10000	0	70
NF kappa B1/RelA/I kappa B alpha	-0.001	0.021	-10000	0	-0.46	1	1
AIFM1	0.003	0.052	0.18	27	-10000	0	27
BCL2	-0.048	0.22	-10000	0	-0.82	36	36

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.021	0.03	0.62	1	-10000	0	1
CDKN1A	-0.007	0.037	-10000	0	-10000	0	0
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
FOXO3	0	0.007	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.024	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	0.006	0.033	-10000	0	-0.31	5	5
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.02	-10000	0	-10000	0	0
PPARGC1A	-0.35	0.41	-10000	0	-0.82	215	215
FHL2	-0.053	0.22	-10000	0	-0.82	39	39
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.031	-10000	0	-0.63	1	1
HIST2H4A	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/FOXO3a	0	0.026	-10000	0	-0.55	1	1
SIRT1	0.001	0.039	-10000	0	-0.82	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.027	-10000	0	-0.54	1	1
SIRT1/Histone H1b	-0.005	0.048	-10000	0	-0.33	9	9
apoptosis	0	0.029	0.54	1	-10000	0	1
SIRT1/PGC1A	-0.24	0.28	-10000	0	-0.55	215	215
p53/SIRT1	0.005	0.044	-10000	0	-0.63	1	1
SIRT1/FOXO4	0.001	0.027	-10000	0	-0.53	1	1
FOXO1/FHL2/SIRT1	-0.039	0.14	-10000	0	-0.5	40	40
HIST1H1E	0.016	0.051	-10000	0	-0.36	8	8
SIRT1/p300	0.001	0.031	-10000	0	-0.63	1	1
muscle cell differentiation	0	0.031	0.55	1	-10000	0	1
TP53	0.002	0.013	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.029	-10000	0	-0.54	1	1
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.037	-10000	0	-0.63	1	1
ACSS2	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/PCAF/MYOD	0	0.031	-10000	0	-0.55	1	1

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0.12	-10000	0	-0.57	9	9
UGCG	-0.044	0.18	-10000	0	-0.8	24	24
AKT1/mTOR/p70S6K/Hsp90/TERT	0.02	0.13	-10000	0	-0.41	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.023	0.18	-10000	0	-0.78	24	24
mol:DAG	0	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.059	0.14	-10000	0	-0.46	35	35
FRAP1	0.001	0.2	-10000	0	-0.54	35	35
FOXO3	0.019	0.16	-10000	0	-0.61	17	17
AKT1	0.01	0.18	-10000	0	-0.62	21	21
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	-0.005	0.023	-10000	0	-10000	0	0
SGMS1	-0.005	0.023	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.046	-10000	0	-0.56	3	3
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.003	0.16	-10000	0	-0.44	36	36
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.02	0.052	-10000	0	-0.63	3	3
RPS6KB1	0.016	0.041	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.012	5	5
JAK3	-0.067	0.14	-10000	0	-0.31	124	124
PIK3R1	0.015	0.005	-10000	0	-10000	0	0
JAK1	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MYC	0.007	0.22	-10000	0	-0.94	18	18
MYB	-0.015	0.2	-10000	0	-1.3	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.16	-10000	0	-0.55	24	24
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.037	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.008	0.16	-10000	0	-0.53	24	24
Rac1/GDP	0.024	0.043	-10000	0	-0.5	3	3
T cell proliferation	0.017	0.15	-10000	0	-0.51	21	21
SHC1	0.013	0.004	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.011	-10000	0	-0.051	16	16
PRKCZ	0.016	0.15	-10000	0	-0.53	21	21
NF kappa B1 p50/RelA	-0.058	0.14	-10000	0	-0.53	19	19
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0	0.13	-10000	0	-0.6	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.045	0.19	-10000	0	-0.57	49	49
IL2RB	-0.013	0.13	-10000	0	-0.5	27	27
TERT	0	0.032	-10000	0	-0.31	5	5
E2F1	-0.004	0.075	-10000	0	-0.45	10	10
SOS1	0.013	0.004	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.024	16	-10000	0	16
PTPN11	0.011	0.038	-10000	0	-0.82	1	1
IL2RG	-0.045	0.19	-10000	0	-0.54	53	53
actin cytoskeleton organization	0.017	0.15	-10000	0	-0.51	21	21
GRB2	0.013	0.004	-10000	0	-10000	0	0
IL2	0.006	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.066	-10000	0	-0.82	3	3
Rac1/GTP	0.031	0.042	-10000	0	-0.48	3	3
LCK	-0.008	0.11	-10000	0	-0.43	26	26
BCL2	-0.026	0.28	-10000	0	-0.82	48	48

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	0.005	0.051	-9999	-0.31	12	12
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.022	0.017	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.82	16	16
mol:Sphinganine-1-P	0.019	0.035	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.002	0.014	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.013	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.011	-9999	-10000	0	0
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
GNAI1	0.012	0.038	-9999	-0.82	1	1
S1P/S1P5/G12	-0.004	0.028	-9999	-0.48	1	1
S1P/S1P3/Gq	-0.05	0.15	-9999	-0.31	121	121
S1P/S1P4/Gi	0.031	0.068	-9999	-0.32	17	17
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	114	114
GNA15	-0.014	0.095	-9999	-0.33	39	39
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.004	0.12	-9999	-0.82	10	10
ABCC1	0.013	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
ITGA4	0.002	0.078	-9999	-0.44	12	12
alpha4/beta7 Integrin	-0.031	0.12	-9999	-0.62	16	16
alpha4/beta1 Integrin	-0.008	0.056	-9999	-0.63	3	3

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.044	0.12	0.33	1	-0.36	61	62
FRAP1	0.008	0.027	-10000	0	-10000	0	0
AKT1	-0.01	0.11	0.24	1	-0.3	61	62
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.028	0.078	-10000	0	-0.5	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.008	0.023	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.023	0.066	-10000	0	-0.45	3	3
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.036	0.14	-10000	0	-0.42	59	59
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.009	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.009	0.061	-10000	0	-0.35	3	3
MAP3K5	0.011	0.021	-10000	0	-0.45	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.021	-10000	0	-0.45	1	1
mol:LY294002	0	0.001	0.001	2	-0.002	58	60
EIF4B	0.016	0.055	-10000	0	-0.34	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.014	0.039	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.026	0.14	-10000	0	-0.39	61	61
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.041	0.18	1	-0.28	2	3
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.023	0.065	-10000	0	-0.44	3	3
mol:Amino Acids	0	0.001	0.001	2	-0.002	58	60
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.041	0.12	0.26	1	-0.33	61	62
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.034	-10000	0	-0.62	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.03	0.084	-10000	0	-0.56	3	3
tumor necrosis factor receptor activity	0	0.001	0.002	58	-0.001	2	60
RPS6	0.013	0	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	-0.047	0.15	-10000	0	-0.46	59	59
INS	0	0	-10000	0	-10000	0	0
PTEN	0.011	0.037	-10000	0	-0.82	1	1
PDK2	-0.04	0.11	0.26	1	-0.32	61	62
EIF4EBP1	0.012	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
PPP2R5D	0.015	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.018	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.004	3	4
EEF2	0.018	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.019	0.008	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	-0.035	0.14	-10000	0	-0.63	27	27
ATM	0.012	0.038	-10000	0	-0.82	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.012	0.038	-10000	0	-0.82	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.03	-10000	0	-0.44	2	2
protein ubiquitination	-0.026	0.1	-10000	0	-0.45	28	28
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	-0.003	0.042	-10000	0	-0.54	3	3
MRE11A	0.008	0.065	-10000	0	-0.82	3	3
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.013	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0	0	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.035	0.14	-10000	0	-0.63	27	27
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	0	0.065	-10000	0	-0.31	20	20
DNA repair	0.052	0.1	-10000	0	-0.41	1	1
BRCA1/BARD1/ubiquitin	-0.035	0.14	-10000	0	-0.63	27	27
BARD1/DNA-PK	-0.027	0.11	-10000	0	-0.49	27	27
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.035	0.14	0.62	27	-10000	0	27
BRCA1/BARD1/CTIP/M/R/N Complex	0.02	0.091	-10000	0	-0.33	31	31
BRCA1/BACH1/BARD1/TopBP1	-0.03	0.12	-10000	0	-0.54	27	27
BRCA1/BARD1/P53	-0.028	0.11	-10000	0	-0.49	28	28
BARD1/CSTF1/BRCA1	-0.03	0.12	-10000	0	-0.54	27	27
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.033	0.19	-10000	0	-0.82	27	27
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.03	0.12	-10000	0	-0.54	27	27
BRCA1/BARD1/UbcH7	-0.03	0.12	-10000	0	-0.54	27	27
BRCA1/BARD1/RAD51/PCNA	-0.028	0.11	-10000	0	-0.49	27	27
BARD1/DNA-PK/P53	-0.025	0.1	-10000	0	-0.46	27	27
BRCA1/BARD1/Ubiquitin	-0.035	0.14	-10000	0	-0.63	27	27
BRCA1/BARD1/CTIP	-0.028	0.11	-10000	0	-0.49	28	28
FA complex	0.038	0.024	-10000	0	-10000	0	0
BARD1/EWS	-0.035	0.14	-10000	0	-0.63	27	27
RBBP8	0.023	0.029	-10000	0	-0.63	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.028	0.11	0.49	28	-10000	0	28
BRCA1/BARD1	-0.026	0.11	-10000	0	-0.46	28	28
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.035	0.14	-10000	0	-0.64	27	27
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.012	0.021	-10000	0	-0.31	2	2
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.035	0.14	-10000	0	-0.63	27	27
EWSR1	0.013	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.004	0.12	-10000	0	-0.82	10	10
ANTXR2	0.008	0.065	-10000	0	-0.82	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.016	-10000	0	-0.1	13	13
monocyte activation	-0.047	0.17	-10000	0	-0.48	61	61
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.014	-10000	0	-10000	0	0
MAP2K7	-0.002	0.014	-10000	0	-10000	0	0
MAP2K6	-0.014	0.075	-10000	0	-0.5	11	11
CYAA	0.003	0.08	-10000	0	-0.48	13	13
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.024	0.13	-10000	0	-0.46	40	40
Channel	-0.014	0.082	-10000	0	-0.51	13	13
NLRP1	-0.004	0.034	-10000	0	-0.49	2	2
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.016	0.1	13	-10000	0	13
MAPK3	-0.002	0.014	-10000	0	-10000	0	0
MAPK1	-0.002	0.014	-10000	0	-10000	0	0
PGR	-0.022	0.086	-10000	0	-0.46	15	15
PA/Cellular Receptors	-0.015	0.088	-10000	0	-0.55	13	13
apoptosis	-0.003	0.016	-10000	0	-0.1	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.079	-10000	0	-0.48	13	13
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.09	0.27	-10000	0	-0.77	64	64
VCAM1	-0.048	0.17	-10000	0	-0.48	61	61
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.024	0.1	11	-10000	0	11
IL18	-0.01	0.085	-10000	0	-0.41	14	14
negative regulation of macrophage activation	-0.003	0.016	-10000	0	-0.1	13	13
LEF	-0.003	0.016	-10000	0	-0.1	13	13
CASP1	-0.003	0.02	-10000	0	-0.22	2	2
mol:cAMP	-0.003	0.019	-10000	0	-10000	0	0
necrosis	-0.003	0.016	-10000	0	-0.1	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.013	0.078	-10000	0	-0.48	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.033	0.3	1	-0.47	2	3
DAPP1	-0.053	0.14	-10000	0	-0.48	13	13
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.057	0.18	-10000	0	-0.49	31	31
mol:DAG	-0.004	0.096	-10000	0	-0.28	15	15
HRAS	0.013	0.021	-10000	0	-0.31	2	2
RAP1A	0.014	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.023	0.035	-10000	0	-0.46	1	1
PLCG2	0.013	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
ARF5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.014	0.27	1	-10000	0	1
ARF1/GTP	-0.001	0.022	0.28	1	-0.32	1	2
RHOA	0.013	0	-10000	0	-10000	0	0
YES1	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP	0	0.013	0.26	1	-10000	0	1
ADAP1	0	0.013	0.26	1	-10000	0	1
ARAP3	0	0.014	0.27	1	-10000	0	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PREX1	0.013	0	-10000	0	-10000	0	0
ARHGEF6	0.012	0.038	-10000	0	-0.82	1	1
ARHGEF7	0.013	0	-10000	0	-10000	0	0
ARF1	0.013	0	-10000	0	-10000	0	0
NRAS	0.014	0.001	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
FGR	0.011	0.029	-10000	0	-0.31	4	4
mol:Ca2+	0.007	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.32	277	277
ZAP70	-0.022	0.16	-10000	0	-0.6	28	28
mol:IP3	0.005	0.071	-10000	0	-0.21	4	4
LYN	0.013	0	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.035	-10000	0	-0.46	1	1
RhoA/GDP	-0.001	0.019	0.28	1	-10000	0	1
PDK1/Src/Hsp90	-0.003	0.035	-10000	0	-0.54	2	2
BLNK	0.013	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.038	0.037	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
PLEKHA2	0.022	0.041	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.79	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.015	0.3	1	-10000	0	1
RhoA/GTP	0	0.013	0.26	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.048	0.16	-10000	0	-0.6	13	13
BLK	-0.24	0.37	-10000	0	-0.75	165	165
PDPK1	0.01	0.053	-10000	0	-0.82	2	2
CYTH1	0	0.013	0.26	1	-10000	0	1
HCK	-0.007	0.08	-10000	0	-0.31	31	31
CYTH3	-0.002	0.034	0.26	1	-0.49	2	3
CYTH2	0	0.013	0.26	1	-10000	0	1
KRAS	0.014	0.001	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.014	0.095	-10000	0	-0.62	11	11
SGK1	-0.015	0.11	-10000	0	-0.69	11	11
INPP5D	-0.003	0.072	-10000	0	-0.31	25	25
mol:GDP	0.015	0.037	-10000	0	-0.49	1	1
SOS1	0.013	0	-10000	0	-10000	0	0
SYK	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.019	0.29	1	-10000	0	1
mol:PI-3-4-5-P3	0	0.018	0.36	1	-10000	0	1
ARAP3/RAP1A/GTP	0	0.013	0.26	1	-10000	0	1
VAV1	-0.013	0.1	-10000	0	-0.36	35	35
mol:PI-3-4-P2	0.013	0.05	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0	0.006	-10000	0	-10000	0	0
PLEKHA1	0.022	0.041	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.035	-10000	0	-0.46	1	1
LAT	0.006	0.076	-10000	0	-0.72	5	5
Rac1/GTP	-0.006	0.054	-10000	0	-0.47	2	2
ITK	-0.055	0.14	-10000	0	-0.43	59	59
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.013	0.12	-10000	0	-0.39	16	16
LCK	-0.01	0.11	-10000	0	-0.43	26	26
BTK	-0.013	0.061	0.26	1	-0.43	8	9

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.046	0.059	-10000	0	-10000	0	0
NFATC2	-0.02	0.097	-10000	0	-0.3	28	28
NFATC3	0.018	0.012	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.011	0.091	-10000	0	-0.31	26	26
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.002	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.026	0.096	-10000	0	-0.59	9	9
BCL2/BAX	-0.047	0.16	-10000	0	-0.63	36	36
CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.006	0.01	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.015	0.087	-10000	0	-0.56	4	4
Calcineurin A alpha-beta B1/BCL2	-0.048	0.22	-10000	0	-0.82	36	36
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.015	0.086	0.55	4	-10000	0	4
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.013	0	-10000	0	-10000	0	0
XPO1	0.013	0.001	-10000	0	-10000	0	0
SFN	-0.21	0.18	-10000	0	-0.33	314	314
MAP3K8	-0.004	0.1	-10000	0	-0.82	8	8
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.12	0.16	-10000	0	-0.5	23	23
CABIN1	0.011	0.092	-10000	0	-0.32	26	26
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
MAP3K1	0.013	0	-10000	0	-10000	0	0
CAMK4	-0.004	0.11	-10000	0	-0.55	15	15
mol:Ca2+	-0.005	0.009	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.009	0.12	-10000	0	-0.82	11	11
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.007	0.05	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.006	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.015	0.05	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.047	-10000	0	-10000	0	0
PRKCB	-0.027	0.13	-10000	0	-0.36	53	53
PRKCE	0.005	0.084	-10000	0	-0.82	5	5
JNK2/NFAT4	0.022	0.014	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.013	0.001	-10000	0	-10000	0	0
PRKCZ	0.01	0.006	-10000	0	-10000	0	0
PRKCA	-0.026	0.18	-10000	0	-0.82	23	23
PRKCG	0.005	0.022	-10000	0	-0.31	2	2
PRKCQ	0.005	0.084	-10000	0	-0.82	5	5
FKBP38/BCL2	-0.046	0.16	-10000	0	-0.63	36	36
EP300	0.01	0.007	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.031	0.089	-10000	0	-0.41	3	3
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.01	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.011	0.07	-10000	0	-0.56	7	7
NFATc/ERK1	0.052	0.056	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.025	0.095	-10000	0	-0.58	9	9
NR4A1	-0.18	0.36	-10000	0	-0.73	144	144
GSK3B	0.01	0.006	-10000	0	-10000	0	0
positive T cell selection	0.018	0.012	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.037	0.064	-10000	0	-0.4	5	5
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
AKAP5	0.013	0	-10000	0	-10000	0	0
MEF2D	0.01	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.041	0.062	-10000	0	-10000	0	0
CREBBP	0.01	0.007	-10000	0	-10000	0	0
BCL2	-0.048	0.22	-10000	0	-0.82	36	36

×

Retinoic acid receptors-mediated 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
HDAC1	0.013	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-0.31	1	1
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.062	-10000	0	-0.34	7	7
KAT2B	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
AKT1	0.01	0.087	0.24	5	-0.4	16	21
RAR alpha/9cRA/Cyclin H	-0.024	0.097	-10000	0	-0.42	23	23
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.028	0.069	-10000	0	-0.37	8	8
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.017	0.12	-10000	0	-0.73	11	11
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.021	0.16	-10000	0	-0.63	27	27
NCOA2	-0.067	0.24	-10000	0	-0.82	47	47
NCOA3	0.013	0	-10000	0	-10000	0	0
NCOA1	0.013	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-10000	0	-0.31	1	1
RARG	0.014	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.002	-10000	0	-10000	0	0
MAPK1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.004	0.12	-10000	0	-0.82	11	11
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.038	0.14	-10000	0	-0.67	23	23
RARA	0.005	0.097	-10000	0	-0.35	31	31
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.003	0.14	-10000	0	-0.56	18	18
PRKCA	-0.023	0.18	-10000	0	-0.82	23	23
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.032	0.16	-10000	0	-0.65	27	27
RXRG	-0.12	0.11	-10000	0	-0.53	27	27
RXRA	0.011	0.096	-10000	0	-0.34	31	31
RXRB	0.005	0.1	-10000	0	-0.44	23	23
VDR/Vit D3/DNA	0	0.01	-10000	0	-10000	0	0
RBP1	-0.001	0.1	-10000	0	-0.63	11	11
CRBP1/9-cic-RA	-0.011	0.078	-10000	0	-0.48	11	11
RARB	-0.008	0.14	-10000	0	-0.82	14	14
PRKCG	0.008	0.022	-10000	0	-0.31	2	2
MNAT1	0.013	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.028	0.17	-10000	0	-0.67	27	27
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.01	0.14	-10000	0	-0.55	27	27
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.093	-10000	0	-0.49	9	9
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.032	0.16	-10000	0	-0.65	27	27
positive regulation of DNA binding	-0.023	0.091	-10000	0	-0.39	23	23
NRIP1	-0.027	0.15	-10000	0	-0.63	20	20
RXRs/RARs	-0.04	0.16	-10000	0	-0.64	27	27
RXRs/RXRs/DNA/9cRA	-0.05	0.15	-10000	0	-0.69	23	23
PRKACA	0.013	0	-10000	0	-10000	0	0
CDK7	0.013	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.014	0.058	-10000	0	-0.52	3	3
CCNH	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.012	0.038	-9999	-0.82	1	1
Caspase 8 (4 units)	-0.02	0.059	-9999	-10000	0	0
NEF	-0.01	0.053	-9999	-0.22	25	25
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	-0.004	0.2	-9999	-0.81	26	26
CYCS	-0.003	0.099	-9999	-0.39	5	5
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.033	0.18	-9999	-0.77	22	22
MAP2K7	0.026	0.078	-9999	-10000	0	0
protein ubiquitination	0.039	0.087	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	-0.011	0.1	-9999	-0.42	5	5
NF-kappa-B/RelA/I kappa B alpha	-0.021	0.08	-9999	-0.52	1	1
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.021	0.08	-9999	-0.52	1	1
MAPK8	0.023	0.099	-9999	-0.41	11	11
APAF1	0.012	0.038	-9999	-0.82	1	1
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.012	0.093	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.1	-9999	-0.36	11	11
CHUK	0.039	0.092	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.021	-9999	-0.46	1	1
TCRz/NEF	-0.054	0.17	-9999	-0.52	47	47
TNF	-0.09	0.27	-9999	-0.77	64	64
FASLG	-0.061	0.27	-9999	-0.84	47	47
NFKB1	0.007	0.047	-9999	-0.81	1	1
TNFR1A/BAG4/TNF-alpha	-0.067	0.18	-9999	-0.54	59	59
CASP6	-0.003	0.044	-9999	-10000	0	0
CASP7	0.031	0.16	-9999	-0.62	25	25
RELA	0.009	0.029	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.031	0.16	-9999	-0.62	25	25
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.028	-9999	-0.63	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.099	-9999	-0.37	2	2
APAF-1/Caspase 9	-0.045	0.12	-9999	-0.52	25	25
BCL2	-0.002	0.15	-9999	-0.4	44	44

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.033	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
ENAH	0.07	0.009	-9999	-10000	0	0
EGFR	0.007	0.075	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
MYO6	0.041	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0	0	-9999	-10000	0	0
AQP5	-0.038	0.13	-9999	-0.59	25	25
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.04	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.074	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	76	76
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.073	0.19	-9999	-0.59	60	60
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GDP	0	0.005	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.048	0.036	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.041	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.009	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.065	0.15	-9999	-0.42	74	74
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.047	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.18	0.35	-9999	-0.82	113	113
DIAPH1	0	0.002	-9999	-10000	0	0
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0.005	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.047	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.039	0.064	-9999	-0.42	9	9
Ephrin A1/EPHA2	-0.001	0.008	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.038	0.074	-9999	-10000	0	0
HGF/MET	-0.1	0.16	-9999	-0.47	74	74
HGF	-0.11	0.3	-9999	-0.82	74	74
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.033	0	-9999	-10000	0	0
actin cable formation	0.085	0.022	-9999	-10000	0	0
KIAA1543	0.047	0.021	-9999	-0.42	1	1
KIFC3	0.041	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.04	0.007	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.041	0	-9999	-10000	0	0
PIP5K1C	0.041	0	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.064	0.019	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.099	0.18	-9999	-0.42	113	113
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	179	179
PLEKHA7	0.04	0.022	-9999	-0.44	1	1
mol:GTP	-0.001	0.01	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.067	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.033	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.047	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.033	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.019	0.087	-10000	0	-0.43	12	12
ACTA1	0.011	0.11	-10000	0	-0.54	12	12
NUMA1	0.019	0.087	-10000	0	-0.43	12	12
SPTAN1	0.015	0.11	-10000	0	-0.58	10	10
LIMK1	0.015	0.11	-10000	0	-0.58	10	10
BIRC3	-0.036	0.19	-10000	0	-0.67	35	35
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.012	0.021	-10000	0	-0.31	2	2
CASP10	0	0.12	-10000	0	-0.58	14	14
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	0.019	0.087	-10000	0	-0.43	12	12
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.016	0.11	-10000	0	-0.57	10	10
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	0.016	0.11	-10000	0	-0.58	10	10
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.057	0.22	-10000	0	-0.64	60	60
BID	-0.01	0.066	-10000	0	-0.3	12	12
MAP3K1	0.014	0.041	-10000	0	-0.24	1	1
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.028	-10000	0	-0.62	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.013	0.11	-10000	0	-0.56	11	11
CASP9	0.013	0	-10000	0	-10000	0	0
DNA repair	-0.016	0.051	0.17	1	-0.23	22	23
neuron apoptosis	0.023	0.015	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.022	0.1	-10000	0	-0.56	10	10
APAF1	0.012	0.037	-10000	0	-0.82	1	1
CASP6	0.022	0.061	-10000	0	-0.37	5	5
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.023	0.1	-10000	0	-0.56	10	10
CASP7	0.009	0.08	0.34	25	-10000	0	25
KRT18	0.017	0.018	-10000	0	-10000	0	0
apoptosis	0.026	0.11	-10000	0	-0.52	12	12
DFFA	0.015	0.11	-10000	0	-0.56	11	11
DFFB	0.015	0.11	-10000	0	-0.58	10	10
PARP1	0.016	0.052	0.23	22	-0.18	1	23
actin filament polymerization	-0.023	0.1	0.53	10	-10000	0	10
TNF	-0.09	0.27	-10000	0	-0.77	64	64
CYCS	0.005	0.044	-10000	0	-0.22	12	12
SATB1	0.029	0.058	-10000	0	-0.36	4	4
SLK	0.013	0.12	-10000	0	-0.62	12	12
p15 BID/BAX	-0.002	0.06	-10000	0	-0.34	3	3
CASP2	0.006	0.12	-10000	0	-0.46	11	11
JNK cascade	-0.014	0.041	0.24	1	-10000	0	1
CASP3	0.008	0.12	-10000	0	-0.57	12	12
LMNB2	0.021	0.075	-10000	0	-0.3	4	4
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.49	25	25
negative regulation of DNA binding	-0.056	0.22	-10000	0	-0.64	60	60
stress fiber formation	0.013	0.12	-10000	0	-0.6	12	12
GZMB	-0.013	0.13	-10000	0	-0.67	14	14
CASP1	0.016	0.031	-10000	0	-0.45	2	2
LMNB1	0.021	0.076	-10000	0	-0.3	4	4
APP	0.023	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	0.023	0.094	0.26	12	-0.47	10	22
LMNA	0.021	0.075	-10000	0	-0.3	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.003	0.12	-10000	0	-0.49	11	11
LRDD	0.013	0	-10000	0	-10000	0	0
SREBF1	0.015	0.11	-10000	0	-0.58	10	10
APAF-1/Caspase 9	0.004	0.041	-10000	0	-0.39	1	1
nuclear fragmentation during apoptosis	0.019	0.086	-10000	0	-0.42	12	12
CFL2	0.023	0.1	-10000	0	-0.54	10	10
GAS2	0.01	0.12	-10000	0	-0.55	16	16
positive regulation of apoptosis	0.023	0.078	-10000	0	-0.3	4	4
PRF1	0	0.1	-10000	0	-0.7	9	9

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.022	0.092	-9999	-0.51	1	1
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.28	0.45	-9999	-0.92	151	151
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	-0.001	0.069	-9999	-10000	0	0
ER alpha/Oestrogen	-0.043	0.14	-9999	-0.6	25	25
NFX1/SIN3/HDAC complex	0.047	0.026	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	76	76
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.007	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.035	0.068	-9999	-0.48	1	1
SAP18	0.014	0	-9999	-10000	0	0
MRN complex	-0.003	0.042	-9999	-0.54	3	3
WT1	-0.025	0.1	-9999	-0.31	53	53
WRN	0.012	0.038	-9999	-0.82	1	1
SP1	0.015	0.003	-9999	-10000	0	0
SP3	0.014	0.002	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.028	0.053	-9999	-10000	0	0
Mad/Max	0.006	0.01	-9999	-10000	0	0
TERT	-0.023	0.093	-9999	-0.52	1	1
CCND1	-0.014	0.093	-9999	-0.57	1	1
MAX	0.014	0.002	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
RBBP4	0.008	0.065	-9999	-0.82	3	3
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
Telomerase/911	0.036	0.019	-9999	-10000	0	0
CDKN1B	-0.039	0.19	-9999	-0.52	63	63
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.001	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.82	110	110
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.003	0.006	-9999	-10000	0	0
FOS	-0.2	0.36	-9999	-0.82	128	128
IFN-gamma/IRF1	-0.085	0.2	-9999	-0.61	64	64
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.013	0.015	-9999	-0.31	1	1
Telomerase	0.014	0.071	-9999	-0.48	5	5
IRF1	0.018	0.015	-9999	-0.3	1	1
ESR1	-0.047	0.19	-9999	-0.52	55	55
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.025	-9999	-0.55	1	1
ubiquitin-dependent protein catabolic process	0.052	0.027	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.053	0.027	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC2	0.015	0.003	-9999	-10000	0	0
ATM	-0.001	0.025	-9999	-0.56	1	1
SMAD3	0.02	0.03	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.014	0.002	-9999	-10000	0	0
MRE11A	0.008	0.065	-9999	-0.82	3	3
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.031	0.064	-9999	-10000	0	0
NR2F2	0.012	0.002	-9999	-10000	0	0
MAPK3	0.017	0.006	-9999	-10000	0	0
MAPK1	0.017	0.006	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.007	0.044	-9999	-0.31	9	9
NFKB1	0.012	0.038	-9999	-0.82	1	1
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.025	-9999	-0.56	1	1
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.007	0.075	-9999	-0.82	4	4
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.097	0.22	-9999	-0.62	74	74
MYC	-0.008	0.13	-9999	-0.82	13	13
IL2	0.006	0.007	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.007	0.044	-9999	-0.31	9	9
TRF2/BLM	0	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.016	0.079	-9999	-10000	0	0
SP1/HDAC2	0.023	0.006	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.028	0.053	-9999	-10000	0	0
Smad3/Myc	0.009	0.096	-9999	-0.55	13	13
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.099	0.28	-9999	-0.71	78	78
Telomerase/PinX1	-0.028	0.053	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.022	0.037	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.028	0.053	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.003	0.035	-9999	-0.45	3	3
TRF2/WRN	-0.001	0.027	-9999	-0.59	1	1
Telomerase/hnRNP C1/C2	-0.028	0.053	-9999	-10000	0	0
E2F1	-0.085	0.15	-9999	-10000	0	0
ZNFX1	0.014	0	-9999	-10000	0	0
PIF1	0.002	0.088	-9999	-0.59	9	9
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.039	0.016	-10000	0	-10000	0	0
CDKN1A	0.034	0.031	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
FOXO3	0.039	0.016	-10000	0	-10000	0	0
AKT1	-0.001	0.014	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
AKT3	0.016	0.03	-10000	0	-0.45	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.039	0.016	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.023	-10000	0	-0.42	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.012	0.038	-10000	0	-0.82	1	1
RAF1	0.013	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.022	0.41	1	-10000	0	1
TSC1	0.039	0.016	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
AKT1/RAF1	0.038	0.016	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.032	0.016	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.039	0.016	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.055	0.2	-10000	0	-0.55	69	69
MAP3K5	0.012	0.038	-10000	0	-0.82	1	1
MAPKAP1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.035	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
AKT1S1	0.039	0.016	-10000	0	-10000	0	0
CASP9	0.039	0.016	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.045	0.015	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.003	0.035	-10000	0	-0.54	2	2
YWHAE	0.013	0	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
AKT2/p21CIP1	-0.005	0.029	-10000	0	-0.41	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.039	0.016	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.015	-10000	0	-10000	0	0
mTORC2	-0.001	0.023	-10000	0	-0.51	1	1
AKT2	0.016	0.03	-10000	0	-0.45	2	2
FOXO1-3a-4/14-3-3 family	0.025	0.041	-10000	0	-10000	0	0
PDPK1	0.01	0.053	-10000	0	-0.82	2	2
MDM2	0.039	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.016	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.051	0.015	-10000	0	-10000	0	0
TSC1/TSC2	0.046	0.015	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.011	-10000	0	-10000	0	0
glucose import	-0.064	0.21	-10000	0	-0.52	84	84
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.033	0.012	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.064	0.22	-10000	0	-0.52	84	84
GSK3A	0.039	0.016	-10000	0	-10000	0	0
FOXO1	0.039	0.016	-10000	0	-10000	0	0
GSK3B	0.039	0.016	-10000	0	-10000	0	0
SFN	-0.21	0.18	-10000	0	-0.33	314	314
G1/S transition of mitotic cell cycle	0.046	0.015	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.001	0.051	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
KPNA1	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.005	0.13	-10000	0	-0.56	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
BAD	0.018	0.046	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.67	35	35
BAX	0.017	0.047	-10000	0	-0.22	1	1
EnzymeConsortium:3.1.4.12	0.004	0.034	-10000	0	-0.12	11	11
IKBKB	0.013	0.12	-10000	0	-0.52	11	11
MAP2K2	0.027	0.056	-10000	0	-0.36	2	2
MAP2K1	0.027	0.056	-10000	0	-0.36	2	2
SMPD1	0.01	0.034	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.013	0.13	-10000	0	-0.53	11	11
MAP2K4	0.024	0.047	-10000	0	-10000	0	0
protein ubiquitination	0.014	0.12	-10000	0	-0.52	11	11
EnzymeConsortium:2.7.1.37	0.031	0.062	-10000	0	-0.37	2	2
response to UV	0	0.001	-10000	0	-0.003	2	2
RAF1	0.022	0.057	-10000	0	-0.39	2	2
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.048	-10000	0	-0.17	11	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.017	0.047	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.013	0	-10000	0	-10000	0	0
MAPK3	0.03	0.056	-10000	0	-0.35	2	2
MAPK1	0.03	0.056	-10000	0	-0.35	2	2
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.005	0.13	-10000	0	-0.56	11	11
KSR1	0.016	0.056	-10000	0	-0.42	2	2
MAPK8	0.021	0.081	-10000	0	-0.43	11	11
TRAF2	0.013	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.013	0.12	-10000	0	-0.52	11	11
TNF R/SODD	-0.001	0.028	-10000	0	-0.63	1	1
TNF	-0.09	0.27	-10000	0	-0.77	64	64
CYCS	0.027	0.056	0.16	30	-10000	0	30
IKBKG	0.013	0.12	-10000	0	-0.52	11	11
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.14	-10000	0	-0.44	25	25
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AIFM1	0.027	0.056	0.16	30	-10000	0	30
TNF/TNF R/SODD	-0.067	0.18	-10000	0	-0.54	59	59
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.033	-10000	0	-10000	0	0
NSMAF	0.005	0.13	-10000	0	-0.55	11	11
response to hydrogen peroxide	0	0.001	-10000	0	-0.003	2	2
BCL2	-0.048	0.22	-10000	0	-0.82	36	36

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.038	-9999	-0.82	1	1
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.058	-9999	-0.33	1	1
GNAO1	-0.015	0.15	-9999	-0.82	16	16
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.005	0.029	-9999	-0.47	1	1
AKT3	0.048	0.05	-9999	-0.56	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.037	-9999	-0.82	1	1
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.013	0.038	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.036	0.067	-9999	-0.31	16	16
MAPK3	0.042	0.063	-9999	-10000	0	0
MAPK1	0.042	0.063	-9999	-10000	0	0
JAK2	0.045	0.065	-9999	-0.42	1	1
CXCR4	0.041	0.064	-9999	-10000	0	0
FLT1	0.015	0.038	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.042	0.064	-9999	-10000	0	0
S1P/S1P3/Gi	0.036	0.067	-9999	-0.32	16	16
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.01	0.051	-9999	-10000	0	0
VEGFA	0.012	0.065	-9999	-0.82	3	3
S1P/S1P2/Gi	0.03	0.068	-9999	-0.32	16	16
VEGFR1 homodimer/VEGFA homodimer	0.024	0.067	-9999	-0.79	3	3
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.067	0.17	-9999	-0.35	121	121
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.015	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	114	114
GNA15	-0.014	0.095	-9999	-0.33	39	39
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.004	0.12	-9999	-0.82	10	10
Rac1/GTP	-0.01	0.051	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.008	0.066	-9999	-0.82	3	3
positive regulation of NF-kappaB transcription factor activity	-0.004	0.05	-9999	-0.62	3	3
MAP2K4	0.047	0.031	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.008	0.065	-9999	-0.82	3	3
SMPD1	-0.002	0.023	-9999	-0.29	3	3
IKBKG	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.004	0.05	-9999	-0.63	3	3
TRAIL/TRAILR3	-0.06	0.1	-9999	-0.68	3	3
TRAIL/TRAILR1	-0.008	0.069	-9999	-0.63	6	6
TRAIL/TRAILR4	-0.004	0.05	-9999	-0.63	3	3
TRAIL/TRAILR1/DAP3/GTP	-0.006	0.055	-9999	-0.5	6	6
IKK complex	-0.002	0.017	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.052	-9999	-0.62	3	3
MAP3K1	-0.003	0.027	-9999	-10000	0	0
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.065	-9999	-0.82	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.035	0.041	-9999	-0.33	6	6
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.02	0.052	-9999	-0.62	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.006	0.051	-9999	-0.46	6	6
mol:ceramide	-0.002	0.023	-9999	-0.29	3	3
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.043	0.081	-9999	-0.46	11	11
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.077	0.15	-9999	-0.31	135	135
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.007	0.06	-9999	-0.54	6	6
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.005	0.045	-9999	-0.52	3	3
JNK cascade	-0.004	0.05	-9999	-0.62	3	3
TRAIL (trimer)	0.008	0.066	-9999	-0.82	3	3
TNFRSF10C	-0.077	0.15	-9999	-0.31	135	135
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.006	0.052	-9999	-0.47	6	6
TRAIL/TRAILR2/FADD	-0.004	0.043	-9999	-0.54	3	3
cell death	0.019	0.024	-9999	-0.29	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.037	0.029	-9999	-0.33	3	3
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.013	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.036	-9999	-0.46	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.081	-9999	-0.71	6	6
PDGFRB	0.012	0.038	-9999	-0.82	1	1
SPHK1	-0.008	0.022	-9999	-10000	0	0
mol:S1P	-0.009	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	0.012	0.15	-9999	-0.7	10	10
GNAO1	-0.017	0.15	-9999	-0.82	16	16
PDGFB-D/PDGFRB/PLCgamma1	0.022	0.14	-9999	-0.57	11	11
PLCG1	0.019	0.14	-9999	-0.64	10	10
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.011	0.074	-9999	-0.62	6	6
S1P1/S1P	-0.017	0.067	-9999	-0.5	6	6
negative regulation of cAMP metabolic process	0.013	0.15	-9999	-0.68	10	10
MAPK3	0.005	0.2	-9999	-0.58	44	44
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.006	0.075	-9999	-0.82	4	4
PLCB2	0.03	0.072	-9999	-0.43	6	6
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.054	-9999	-0.41	6	6
receptor internalization	-0.016	0.062	-9999	-0.46	6	6
PTGS2	-0.037	0.34	-9999	-1.1	43	43
Rac1/GTP	-0.014	0.054	-9999	-0.41	6	6
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.065	-9999	-0.82	3	3
negative regulation of T cell proliferation	0.013	0.15	-9999	-0.68	10	10
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.005	-9999	-10000	0	0
MAPK1	0.005	0.2	-9999	-0.58	44	44
S1P1/S1P/PDGFB-D/PDGFRB	0.031	0.088	-9999	-0.49	7	7
ABCC1	0.014	0.002	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.061	0.16	-9999	-0.5	59	59
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.007	0.15	-9999	-0.41	59	59
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.025	0.066	-9999	-10000	0	0
YY1/LSF	0.028	0.05	-9999	-0.52	4	4
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.013	0.13	-9999	-0.36	58	58
I kappa B alpha/HDAC1	0	0.09	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	-0.003	0.12	-9999	-0.32	58	58
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	0	0.09	-9999	-10000	0	0
NuRD/MBD3 Complex	0.049	0.02	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.002	0.11	-9999	-0.29	59	59
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
GATA1	0.008	0.016	-9999	-0.31	1	1
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.022	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.008	0.065	-9999	-0.82	3	3
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	-0.008	0.1	-9999	-0.28	58	58
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.044	0.027	-9999	-10000	0	0
SIN3 complex	-0.001	0.022	-9999	-0.49	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.015	0.084	-9999	-10000	0	0
YY1/HDAC2	0.033	0	-9999	-10000	0	0
YY1/HDAC1	0.033	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.049	0.02	-9999	-10000	0	0
PPARG	-0.06	0.16	-9999	-0.46	63	63
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0	0.09	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.022	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	-0.008	0.1	-9999	-0.28	58	58
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.032	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.027	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.043	-9999	-0.48	4	4
YY1/SAP30/HDAC1	-0.001	0.022	-9999	-0.48	1	1
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.027	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.1	-9999	-0.28	58	58
histone deacetylation	0.049	0.02	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.012	0.085	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	0	0.09	-9999	-10000	0	0
GATA1/HDAC1	0	0.009	-9999	-10000	0	0
GATA1/HDAC3	-0.01	0.09	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.077	0.2	-9999	-0.63	58	58
SIN3/HDAC complex/Mad/Max	0.049	0.023	-9999	-10000	0	0
NuRD Complex	0.058	0.022	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.024	0.065	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0.032	0	-9999	-10000	0	0
HDAC complex	-0.003	0.038	-9999	-0.49	3	3
GATA1/Fog1	0	0.009	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.09	0.27	-9999	-0.77	64	64
negative regulation of cell growth	0.049	0.023	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.049	0.02	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.053	0.14	-9999	-0.44	58	58
SIN3/HDAC complex/NCoR1	0.046	0.026	-9999	-10000	0	0
TFCP2	0.007	0.075	-9999	-0.82	4	4
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.007	0.024	-10000	0	-10000	0	0
AES	0.006	0.02	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	-0.025	0.16	-10000	0	-0.65	28	28
TLE1	0	0.066	-10000	0	-0.8	3	3
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.047	0.039	-10000	0	-10000	0	0
WIF1	-0.034	0.1	-10000	0	-0.31	59	59
beta catenin/RanBP3	0.023	0.092	0.37	26	-10000	0	26
KREMEN2	-0.01	0.083	-10000	0	-0.31	34	34
DKK1	-0.041	0.12	-10000	0	-0.32	79	79
beta catenin/beta TrCP1	0.053	0.037	-10000	0	-10000	0	0
FZD1	0.014	0.001	-10000	0	-10000	0	0
AXIN2	-0.049	0.31	-10000	0	-1.6	19	19
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.063	0.044	0.29	1	-0.41	1	2
Axin1/APC/GSK3	0.007	0.031	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.058	0.019	-10000	0	-10000	0	0
HNF1A	0.006	0.021	-10000	0	-10000	0	0
CTBP1	0.006	0.021	-10000	0	-10000	0	0
MYC	-0.032	0.26	-10000	0	-1.6	13	13
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.035	0.11	-10000	0	-0.55	19	19
NKD1	-0.013	0.14	-10000	0	-0.7	18	18
TCF4	0.006	0.021	-10000	0	-10000	0	0
TCF3	0.006	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.001	0.01	-10000	0	-10000	0	0
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.03	0.12	0.48	28	-10000	0	28
LEF1	-0.002	0.066	-10000	0	-0.42	9	9
DVL1	0.019	0.028	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.067	0.074	-10000	0	-0.46	5	5
DKK1/LRP6/Kremen 2	-0.037	0.077	-10000	0	-0.37	8	8
LRP6	0.014	0.001	-10000	0	-10000	0	0
CSNK1A1	0.006	0.023	0.22	1	-10000	0	1
NLK	0.013	0.004	-10000	0	-10000	0	0
CCND1	-0.001	0.076	-10000	0	-0.8	1	1
WNT1	0.009	0.026	-10000	0	-0.31	3	3
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0	-10000	0	-10000	0	0
FRAT1	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.03	0.06	0.36	14	-10000	0	14
APC	0.038	0.027	-10000	0	-0.46	1	1
WNT1/LRP6/FZD1	0.035	0.037	-10000	0	-10000	0	0
CREBBP	0.006	0.021	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.071	0.055	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	-0.029	0.078	-9999	-0.63	2	2
NFKBIA	0.049	0.023	-9999	-0.47	1	1
BIRC2	0.013	0	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.005	0.02	-9999	-10000	0	0
IKK complex/A20	-0.049	0.13	-9999	-0.64	2	2
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.039	-9999	-0.42	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.002	0.014	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.002	0.035	-9999	-0.54	2	2
NOD2	-0.033	0.12	-9999	-0.33	66	66
NFKB1	0.015	0.037	-9999	-0.81	1	1
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.012	0.038	-9999	-0.82	1	1
TNF/TNFR1A	-0.077	0.2	-9999	-0.63	58	58
TRAF6	0.01	0.053	-9999	-0.82	2	2
PRKCA	-0.026	0.18	-9999	-0.82	23	23
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.09	0.27	-9999	-0.77	64	64
NF kappa B1 p50/RelA	-0.001	0.024	-9999	-0.52	1	1
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.023	-9999	-0.47	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.003	0.016	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.02	0.084	-9999	-0.39	23	23

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.026	0.048	-9999	-0.63	1	1
CLOCK	-0.043	0.21	-9999	-0.82	32	32
TIMELESS/CRY2	-0.005	0.065	-9999	-10000	0	0
DEC1/BMAL1	-0.021	0.063	-9999	-10000	0	0
ATR	0.012	0.038	-9999	-0.82	1	1
NR1D1	-0.057	0.13	-9999	-10000	0	0
ARNTL	-0.02	0.096	-9999	-0.32	46	46
TIMELESS	-0.013	0.074	-9999	-10000	0	0
NPAS2	0.009	0.041	-9999	-0.56	2	2
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.007	0.03	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.007	0.03	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.032	0.15	-9999	-0.56	33	33
BMAL1/CLOCK	-0.056	0.16	-9999	-0.51	32	32
S phase of mitotic cell cycle	-0.026	0.048	-9999	-0.63	1	1
TIMELESS/CHEK1/ATR	-0.026	0.048	-9999	-0.64	1	1
mol:NADPH	-0.007	0.03	-9999	-10000	0	0
PER1/TIMELESS	-0.005	0.065	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.015	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.061	0.13	-10000	0	-10000	0	0
regulation of axonogenesis	-0.01	0.037	0.32	2	-10000	0	2
myoblast fusion	0.024	0.052	-10000	0	-10000	0	0
mol:GTP	-0.027	0.039	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.094	0.11	0.51	1	-10000	0	1
ARF1/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GM1	-0.011	0.034	-10000	0	-10000	0	0
mol:Choline	0.012	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.003	0.064	-10000	0	-10000	0	0
MAPK3	-0.018	0.065	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.094	0.11	-10000	0	-0.52	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.024	0.052	-10000	0	-10000	0	0
ARF1/GDP	0.004	0.059	-10000	0	-10000	0	0
ARF6	-0.002	0.023	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.18	0.17	-10000	0	-0.32	277	277
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.018	0.065	-10000	0	-10000	0	0
actin filament bundle formation	0.025	0.038	-10000	0	-10000	0	0
KALRN	-0.006	0.051	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.025	0.038	-10000	0	-10000	0	0
NME1	0.01	0.007	-10000	0	-10000	0	0
Rac1/GDP	-0.025	0.038	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.027	0.039	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.003	0.064	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.027	0.039	-10000	0	-10000	0	0
ARF6/GTP	-0.027	0.039	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GDP	-0.011	0.065	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.01	0.014	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0	0.033	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.003	0.064	-10000	0	-10000	0	0
ruffle organization	0.01	0.037	-10000	0	-0.32	2	2
regulation of epithelial cell migration	-0.027	0.039	-10000	0	-10000	0	0
PLD2	0	0.033	-10000	0	-10000	0	0
PIP5K1A	0.01	0.037	-10000	0	-0.32	2	2
mol:Phosphatidic acid	0.012	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.003	0.064	-10000	0	-10000	0	0

×

FoxO family signaling

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
G6PC	0.038	0.027	-9999	-10000	0	0
PLK1	0.11	0.11	-9999	-0.73	1	1
CDKN1B	0.15	0.048	-9999	-0.39	1	1
FOXO3	0.11	0.11	-9999	-0.58	4	4
KAT2B	0.025	0.01	-9999	-10000	0	0
FOXO1/SIRT1	0.008	0.038	-9999	-0.59	1	1
CAT	0.1	0.15	-9999	-1.4	3	3
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.028	0.011	-9999	-10000	0	0
FOXO1	0.042	0.018	-9999	-10000	0	0
MAPK10	0.043	0.026	-9999	-0.5	1	1
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.11	0.065	-9999	-0.48	4	4
response to oxidative stress	0.015	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	0.011	0.086	-9999	-0.72	3	3
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.002	-9999	-10000	0	0
BCL2L11	0.041	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.039	0.051	-9999	-0.5	4	4
mol:GDP	0.015	0.013	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.062	-9999	-0.72	1	1
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.041	0.04	-9999	-10000	0	0
MST1	0.023	0.041	-9999	-0.55	2	2
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.063	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.033	0.078	-9999	-0.48	11	11
MAPK9	0.044	0.007	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.005	0.042	-9999	-0.81	1	1
SOD2	0.16	0.073	-9999	-0.79	1	1
RBL2	0.11	0.15	-9999	-1.4	4	4
RAL/GDP	0.034	0.012	-9999	-10000	0	0
CHUK	0.025	0.01	-9999	-10000	0	0
Ran/GTP	0.015	0.002	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.043	0.009	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.063	0.39	-9999	-1.5	32	32
SKP2	0.007	0.075	-9999	-0.82	4	4
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.025	0.01	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.73	1	1
FOXO1-3a-4/beta catenin	-0.003	0.05	-9999	-0.42	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.05	-9999	-0.49	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.007	0.12	-9999	-0.81	11	11
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.003	-9999	-10000	0	0
ZFAND5	0.11	0.055	-9999	-0.47	1	1
SFN	-0.21	0.18	-9999	-0.33	314	314
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.017	0.062	-9999	-10000	0	0
CREBBP	0.014	0.003	-9999	-10000	0	0
FBXO32	0.11	0.1	-9999	-0.73	1	1
BCL6	0.12	0.1	-9999	-0.69	4	4
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.01	0.091	-9999	-0.46	15	15
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.007	0.075	-9999	-0.82	4	4
ITGA4	0.002	0.078	-9999	-0.44	12	12
alpha4/beta7 Integrin/MAdCAM1	-0.032	0.1	-9999	-0.5	17	17
EPO	0.002	0.039	-9999	-0.31	7	7
alpha4/beta7 Integrin	-0.031	0.12	-9999	-0.62	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.008	0.056	-9999	-0.63	3	3
EPO/EPOR (dimer)	-0.007	0.037	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.037	-9999	-0.46	3	3
PIK3CA	0.008	0.065	-9999	-0.82	3	3
PI3K	-0.004	0.049	-9999	-0.63	3	3
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.022	0.067	-9999	-0.62	4	4
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.01	0.089	-9999	-0.35	28	28
cell adhesion	-0.032	0.099	-9999	-0.5	17	17
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.022	0.079	-9999	-0.56	7	7
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.014	0.081	-9999	-0.61	7	7
p130Cas/Crk/Dock1	0.039	0.08	-9999	-0.49	5	5
VCAM1	0.001	0.091	-9999	-0.54	11	11
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.042	-9999	-0.49	3	3
BCAR1	0.03	0.075	-9999	-0.52	7	7
EPOR	0.007	0.046	-9999	-0.31	10	10
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.001	0.039	-9999	-0.48	3	3

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.009	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.011	0.15	-9999	-0.56	33	33
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.039	-9999	-0.41	1	1
NFKBIA	0.024	0.037	-9999	-0.27	6	6
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.027	0.026	-9999	-0.54	1	1
ARRB2	0.018	0	-9999	-10000	0	0
REL	-0.043	0.21	-9999	-0.82	33	33
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.027	-9999	-0.54	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.026	-9999	-0.54	1	1
PIK3CA	0.008	0.065	-9999	-0.82	3	3
NF kappa B1 p50 dimer	0.02	0.029	-9999	-0.63	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.023	0.029	-9999	-0.63	1	1
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.038	-9999	-0.27	6	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.047	0.038	-9999	-0.4	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
PI3K	-0.004	0.049	-9999	-0.63	3	3
NF kappa B1 p50/RelA	0.031	0.039	-9999	-0.27	6	6
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	-0.004	0.028	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.011	0.15	-9999	-0.56	33	33
LCK	-0.01	0.11	-9999	-0.43	26	26
BCL3	0.013	0.015	-9999	-0.31	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.02	0.12	-9999	-0.66	15	15
AKT1	0.084	0.09	-9999	-0.6	7	7
PTK2B	0.036	0.13	-9999	-0.91	5	5
VEGFR2 homodimer/Frs2	0.03	0.097	-9999	-1	4	4
CAV1	-0.009	0.13	-9999	-0.82	13	13
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.011	0.1	-9999	-0.86	6	6
endothelial cell proliferation	0.075	0.1	-9999	-0.61	5	5
mol:Ca2+	0.05	0.1	-9999	-0.73	7	7
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.01	0.099	-9999	-0.82	6	6
RP11-342D11.1	0.041	0.1	-9999	-0.73	7	7
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	-0.006	0.062	-9999	-0.58	5	5
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.008	0.065	-9999	-0.82	3	3
HRAS/GDP	-0.009	0.082	-9999	-0.74	5	5
SH2D2A	-0.032	0.18	-9999	-0.64	34	34
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.008	0.069	-9999	-0.69	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.035	0.14	-9999	-0.56	28	28
VEGFR1 homodimer	0.012	0.037	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.01	0.095	-9999	-0.93	4	4
GRB10	0.05	0.1	-9999	-0.95	4	4
PTPN11	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.01	0.095	-9999	-0.96	4	4
HRAS	0.012	0.021	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.076	-9999	-0.48	5	5
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.01	0.095	-9999	-0.79	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.003	0.091	-9999	-0.82	6	6
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.011	0.1	-9999	-0.86	6	6
mol:GDP	-0.009	0.087	-9999	-0.87	4	4
mol:NADP	0.076	0.067	-9999	-0.56	4	4
eNOS/Hsp90	0.079	0.063	-9999	-0.52	4	4
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.05	0.11	-9999	-0.75	7	7
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.065	-9999	-0.81	3	3
VEGFC	0.012	0.038	-9999	-0.82	1	1
FAK1/Vinculin	0.058	0.11	-9999	-0.71	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.13	-9999	-0.57	21	21
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.019	0.063	-9999	-0.58	4	4
mol:L-citrulline	0.076	0.067	-9999	-0.56	4	4
ITGAV	0.01	0.053	-9999	-0.82	2	2
PIK3CA	0.008	0.065	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.01	0.099	-9999	-0.82	6	6
VEGFR2 homodimer/VEGFA homodimer	-0.012	0.12	-9999	-0.85	7	7
VEGFR2/3 heterodimer	0.024	0.14	-9999	-1	7	7
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.052	0.11	-9999	-0.77	7	7
VEGFR2 homodimer	0.029	0.11	-9999	-1.1	4	4
FLT1	0.012	0.038	-9999	-0.82	1	1
NEDD4	0.012	0.053	-9999	-0.81	2	2
MAPK3	0.042	0.1	-9999	-0.64	8	8
MAPK1	0.042	0.1	-9999	-0.64	8	8
VEGFA145/NRP2	-0.02	0.072	-9999	-0.62	3	3
VEGFR1/2 heterodimer	0.029	0.11	-9999	-1.1	4	4
KDR	0.029	0.11	-9999	-1.1	4	4
VEGFA165/NRP1/VEGFR2 homodimer	-0.018	0.11	-9999	-0.78	7	7
SRC	0.013	0.015	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.045	0.11	-9999	-0.67	8	8
PI3K	-0.012	0.094	-9999	-0.9	4	4
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.011	0.1	-9999	-0.86	6	6
FES	0.05	0.11	-9999	-0.78	7	7
GAB1	-0.01	0.093	-9999	-0.78	6	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.011	0.1	-9999	-0.86	6	6
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.068	0.092	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.011	0.1	-9999	-0.86	6	6
PI3K/GAB1	0.085	0.085	-9999	-0.61	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.01	0.095	-9999	-0.78	6	6
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.014	0.13	-9999	-0.88	8	8
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.05	0.11	-9999	-0.78	7	7
actin cytoskeleton reorganization	-0.035	0.14	-9999	-0.56	28	28
PTK2	0.053	0.12	-9999	-0.79	7	7
EDG1	0.041	0.1	-9999	-0.73	7	7
mol:DAG	0.05	0.11	-9999	-0.75	7	7
CaM/Ca2+	-0.01	0.089	-9999	-0.88	4	4
MAP2K3	0.049	0.12	-9999	-0.98	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.011	0.11	-9999	-1.1	4	4
PLCG1	0.05	0.11	-9999	-0.78	7	7
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.01	0.099	-9999	-0.82	6	6
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.011	0.12	-9999	-0.92	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.011	0.1	-9999	-0.86	6	6
cell migration	0.083	0.096	-9999	-0.69	4	4
mol:PI-3-4-5-P3	-0.01	0.082	-9999	-0.66	6	6
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	0.047	0.096	-9999	-0.68	7	7
mol:NO	0.076	0.067	-9999	-0.56	4	4
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.082	-9999	-0.74	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.049	0.12	-9999	-1.1	4	4
VHL	0.008	0.065	-9999	-0.82	3	3
ITGB3	-0.01	0.14	-9999	-0.82	14	14
NOS3	0.078	0.076	-9999	-0.66	4	4
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.014	0.11	-9999	-0.73	9	9
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.035	0.15	-9999	-0.52	25	25
PRKCB	0.037	0.12	-9999	-0.62	9	9
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.04	0.11	-9999	-0.77	7	7
VEGFR1/2 heterodimer/VEGFA homodimer	-0.011	0.12	-9999	-0.92	6	6
VEGFA165/NRP2	-0.02	0.072	-9999	-0.62	3	3
MAPKKK cascade	-0.009	0.081	-9999	-0.73	5	5
NRP2	-0.013	0.089	-9999	-0.31	39	39
VEGFC homodimer	0.012	0.037	-9999	-0.82	1	1
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.058	0.11	-9999	-0.71	7	7
MAP3K13	0.041	0.14	-9999	-0.61	15	15
PDPK1	0.076	0.091	-9999	-0.71	5	5

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.045	0.002	-9999	-10000	0	0
KLHL20	-0.009	0.021	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.074	0.009	-9999	-10000	0	0
ENAH	0.045	0.002	-9999	-10000	0	0
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	0	0.002	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.001	0.015	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.079	-9999	-0.49	12	12
RAPGEF1	0.058	0.006	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.052	0.006	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.023	0.1	-9999	-0.63	12	12
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.045	0.002	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.016	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.08	0.072	-9999	-0.5	1	1
PI3K	-0.002	0.021	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.17	0.16	-9999	-0.32	277	277
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	-0.001	0.012	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.073	0.009	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.016	-9999	-10000	0	0
CDC42/GDP	0.073	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.027	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.072	0.01	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.002	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.013	0.033	-9999	-0.15	11	11
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.045	0.002	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0.002	-9999	-10000	0	0
WASF2	0.002	0.008	-9999	-10000	0	0
Rap1/GTP	0	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.016	0.074	-9999	-0.46	12	12
CCND1	0.014	0.039	-9999	-0.18	11	11
VAV2	0.056	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.045	0.001	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.015	0.069	-9999	-0.43	12	12
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.044	0.01	-9999	-10000	0	0
PIK3CA	0.008	0.065	-9999	-0.82	3	3
Rac1/GTP	-0.018	0.034	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.051	0.1	-9999	-10000	0	0
CRKL	0.037	0.049	-9999	-0.46	2	2
mol:DAG	0.041	0.052	-9999	-0.37	1	1
HRAS	0.061	0.045	-9999	-0.42	1	1
MAPK8	0.018	0.092	-9999	-0.56	11	11
RAP1A	0.037	0.049	-9999	-0.46	2	2
GAB1	0.037	0.049	-9999	-0.46	2	2
MAPK14	0.03	0.031	-9999	-10000	0	0
EPO	0.005	0.038	-9999	-10000	0	0
PLCG1	0.041	0.052	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.009	0.047	-9999	-0.32	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.037	0.13	-9999	-0.57	27	27
GAB1/SHC/GRB2/SOS1	-0.006	0.029	-9999	-0.45	1	1
EPO/EPOR (dimer)	0.013	0.042	-9999	-10000	0	0
IRS2	0.037	0.049	-9999	-0.46	2	2
STAT1	0.041	0.078	-9999	-10000	0	0
STAT5B	0.042	0.066	-9999	-10000	0	0
cell proliferation	0.026	0.087	-9999	-0.52	11	11
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.009	0.037	-9999	-0.44	2	2
TEC	0.037	0.049	-9999	-0.46	2	2
SOCS3	-0.033	0.19	-9999	-0.8	28	28
STAT1 (dimer)	0.041	0.077	-9999	-0.36	1	1
JAK2	0.011	0.054	-9999	-0.82	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.042	0.055	-9999	-0.49	2	2
EPO/EPOR	0.013	0.042	-9999	-10000	0	0
LYN	0.014	0.004	-9999	-10000	0	0
TEC/VAV2	0.045	0.048	-9999	-0.44	2	2
elevation of cytosolic calcium ion concentration	0.009	0.047	-9999	-0.32	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.028	0.036	-9999	-10000	0	0
mol:IP3	0.041	0.052	-9999	-0.37	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.011	0.037	-9999	-0.47	1	1
SH2B3	0.014	0.005	-9999	-10000	0	0
NFKB1	0.029	0.039	-9999	-0.5	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.019	0.07	-9999	-0.29	29	29
PTPN6	0.03	0.051	-9999	-0.49	2	2
TEC/VAV2/GRB2	0.05	0.047	-9999	-0.48	1	1
EPOR	0.009	0.047	-9999	-0.32	10	10
INPP5D	-0.003	0.072	-9999	-0.31	25	25
mol:GDP	-0.006	0.029	-9999	-0.46	1	1
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
CRKL/CBL/C3G	0.05	0.047	-9999	-0.48	1	1
VAV2	0.037	0.049	-9999	-0.46	2	2
CBL	0.037	0.049	-9999	-0.46	2	2
SHC/Grb2/SOS1	-0.007	0.032	-9999	-0.48	1	1
STAT5A	0.042	0.066	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.052	0.099	-9999	-10000	0	0
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
BTK	0.02	0.089	-9999	-0.48	9	9
BCL2	0.002	0.28	-9999	-0.98	36	36

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.01	0.018	-9999	-10000	0	0
BUB1B	0.018	0.027	-9999	-10000	0	0
PLK1	0.017	0.012	-9999	-10000	0	0
PLK1S1	0.015	0.007	-9999	-10000	0	0
KIF2A	0.023	0.029	-9999	-0.58	1	1
regulation of mitotic centrosome separation	0.017	0.012	-9999	-10000	0	0
GOLGA2	0.013	0	-9999	-10000	0	0
Hec1/SPC24	-0.002	0.076	-9999	-0.28	16	16
WEE1	0.023	0.011	-9999	-10000	0	0
cytokinesis	0.001	0.071	-9999	-0.31	3	3
PP2A-alpha B56	-0.018	0.059	-9999	-0.72	3	3
AURKA	0.016	0.009	-9999	-10000	0	0
PICH/PLK1	0.033	0.017	-9999	-10000	0	0
CENPE	0.019	0.049	-9999	-0.52	3	3
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.023	0.029	-9999	-0.58	1	1
PPP2CA	0.013	0	-9999	-10000	0	0
FZR1	0.013	0	-9999	-10000	0	0
TPX2	0.009	0.021	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
SPC24	-0.01	0.083	-9999	-0.31	34	34
FBXW11	0.013	0	-9999	-10000	0	0
CLSPN	0.005	0.035	-9999	-0.35	2	2
GORASP1	0.013	0	-9999	-10000	0	0
metaphase	0.001	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.009	0.007	-9999	-0.066	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.013	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-9999	-10000	0	0
spindle elongation	0.017	0.012	-9999	-10000	0	0
ODF2	0.013	0.001	-9999	-10000	0	0
BUB1	-0.026	0.068	-9999	-0.8	3	3
TPT1	0.015	0.007	-9999	-10000	0	0
CDC25C	0.012	0.022	-9999	-10000	0	0
CDC25B	0.012	0.021	-9999	-0.31	2	2
SGOL1	0.01	0.018	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.006	0.012	-9999	-10000	0	0
CDC14B	0.004	0.072	-9999	-0.64	6	6
CDC20	0.009	0.039	-9999	-10000	0	0
PLK1/PBIP1	0.002	0.022	-9999	-10000	0	0
mitosis	0	0.002	-9999	-0.022	3	3
FBXO5	0.021	0.021	-9999	-0.4	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.031	0.11	-9999	-0.31	66	66
metaphase plate congression	0.016	0.007	-9999	-10000	0	0
ERCC6L	0.007	0.015	-9999	-10000	0	0
NLP/gamma Tubulin	0.013	0.009	-9999	-10000	0	0
microtubule cytoskeleton organization	0.015	0.007	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-9999	-0.011	3	3
PPP1R12A	0.013	0	-9999	-10000	0	0
interphase	0	0.001	-9999	-0.011	3	3
PLK1/PRC1-2	0.005	0.06	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0	0.004	-9999	-10000	0	0
RAB1A	0.013	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.019	0.039	-9999	-0.47	3	3
mitotic prometaphase	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.036	-9999	-0.32	2	2
microtubule-based process	-0.004	0.063	-9999	-10000	0	0
Golgi organization	0.017	0.012	-9999	-10000	0	0
Cohesin/SA2	-0.001	0.005	-9999	-10000	0	0
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.04	0.12	-9999	-0.31	80	80
APC/C/CDC20	0.021	0.024	-9999	-10000	0	0
PPP2R1A	0.013	0	-9999	-10000	0	0
chromosome segregation	0.002	0.022	-9999	-10000	0	0
PRC1	0.013	0	-9999	-10000	0	0
ECT2	0.022	0.038	-9999	-0.56	2	2
C13orf34	0.019	0.039	-9999	-0.48	3	3
NUDC	0.016	0.007	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.018	0.027	-9999	-10000	0	0
spindle assembly	0.017	0.011	-9999	-10000	0	0
spindle stabilization	0.015	0.007	-9999	-10000	0	0
APC/C/HCDH1	0.012	0.063	-9999	-0.55	6	6
MKLP2/PLK1	-0.004	0.063	-9999	-10000	0	0
CCNB1	0.014	0.001	-9999	-10000	0	0
PPP1CB	0.013	0	-9999	-10000	0	0
BTRC	0.013	0	-9999	-10000	0	0
ROCK2	-0.002	0.12	-9999	-0.52	24	24
TUBG1	0.015	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.008	-9999	-10000	0	0
MLF1IP	0.008	0.033	-9999	-0.22	10	10
INCENP	0.009	0.053	-9999	-0.82	2	2

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.012	0.055	0.38	1	-10000	0	1
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.017	0.15	-10000	0	-0.82	16	16
RhoA/GTP	-0.012	0.056	-10000	0	-0.39	1	1
negative regulation of cAMP metabolic process	0.022	0.07	-10000	0	-0.33	17	17
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	0.007	0.054	-10000	0	-0.38	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.071	-10000	0	-0.33	17	17
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.001	0.025	-10000	0	-10000	0	0
oxygen homeostasis	0.015	0.011	-10000	0	-10000	0	0
TCEB2	0.011	0.026	-10000	0	-0.31	3	3
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.011	0.073	-10000	0	-0.7	4	4
EPO	0.18	0.14	-10000	0	-0.8	2	2
FIH (dimer)	0.029	0.011	-10000	0	-10000	0	0
APEX1	0.027	0.011	-10000	0	-10000	0	0
SERPINE1	0.18	0.17	-10000	0	-0.8	3	3
FLT1	-0.002	0.072	-10000	0	-1.6	1	1
ADORA2A	0.18	0.14	-10000	0	-0.86	2	2
germ cell development	0.19	0.14	-10000	0	-0.84	2	2
SLC11A2	0.19	0.15	-10000	0	-0.89	2	2
BHLHE40	0.18	0.16	-10000	0	-0.89	2	2
HIF1AN	0.029	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.003	0.076	-10000	0	-0.96	2	2
ETS1	0.03	0.003	-10000	0	-10000	0	0
CITED2	-0.089	0.32	-10000	0	-1.2	37	37
KDR	-0.009	0.13	-10000	0	-1.4	4	4
PGK1	0.19	0.15	-10000	0	-0.89	2	2
SIRT1	0.012	0.038	-10000	0	-0.82	1	1
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.2	0.17	-10000	0	-0.96	3	3
EPAS1	0.11	0.1	-10000	0	-0.55	4	4
SP1	0.022	0.002	-10000	0	-10000	0	0
ABCG2	0.19	0.17	-10000	0	-0.88	5	5
EFNA1	0.19	0.15	-10000	0	-0.89	2	2
FXN	0.19	0.14	-10000	0	-0.86	2	2
POU5F1	0.19	0.15	-10000	0	-0.9	2	2
neuron apoptosis	-0.2	0.16	0.91	3	-10000	0	3
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	-0.001	0.14	-10000	0	-0.5	28	28
EGLN2	0.029	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.055	-10000	0	-0.82	2	2
VHL/Elongin B/Elongin C	-0.004	0.048	-10000	0	-0.59	3	3
VHL	0.008	0.065	-10000	0	-0.82	3	3
ARNT	0.027	0.011	-10000	0	-10000	0	0
SLC2A1	0.19	0.14	-10000	0	-0.86	2	2
TWIST1	0.18	0.18	-10000	0	-0.65	10	10
ELK1	0.015	0.026	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.001	0.067	-10000	0	-0.76	2	2
VEGFA	0.19	0.16	-10000	0	-0.84	4	4
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

Figure 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
EEF2K	0.032	0	-9999	-10000	0	0
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.031	0.009	-9999	-10000	0	0
MAPK12	0.019	0.08	-9999	-0.48	12	12
CCND1	0.017	0.035	-9999	-0.25	1	1
p38 gamma/SNTA1	0.025	0.075	-9999	-0.45	11	11
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.019	0.079	-9999	-0.47	12	12
MAP2K6	0.012	0.085	-9999	-0.52	12	12
MAPT	0.024	0.045	-9999	-0.4	3	3
MAPK13	0.024	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.017	0.021	-9999	-0.45	1	1

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.007	-10000	0	-10000	0	0
DOCK1	0.007	0.075	-10000	0	-0.82	4	4
ITGA4	0.002	0.078	-10000	0	-0.44	12	12
RAC1	0.013	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.031	0.12	-10000	0	-0.62	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.047	-10000	0	-0.54	3	3
alpha4/beta7 Integrin/Paxillin	-0.023	0.091	-10000	0	-0.5	15	15
lamellipodium assembly	-0.004	0.058	-10000	0	-0.54	5	5
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
ARF6	0.013	0	-10000	0	-10000	0	0
TLN1	0.013	0	-10000	0	-10000	0	0
PXN	0.024	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.035	-10000	0	-0.42	3	3
cell adhesion	-0.005	0.038	-10000	0	-0.45	3	3
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.005	0.042	-10000	0	-0.49	3	3
ITGB1	0.013	0	-10000	0	-10000	0	0
ITGB7	-0.02	0.14	-10000	0	-0.51	31	31
ARF6/GDP	0.001	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.011	0.069	-10000	0	-0.52	7	7
p130Cas/Crk/Dock1	-0.004	0.049	-10000	0	-0.54	4	4
VCAM1	0.001	0.091	-10000	0	-0.54	11	11
alpha4/beta1 Integrin/Paxillin/Talin	-0.005	0.039	-10000	0	-0.46	3	3
alpha4/beta1 Integrin/Paxillin/GIT1	-0.005	0.039	-10000	0	-0.46	3	3
BCAR1	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.038	0.45	3	-10000	0	3
CBL	0.013	0	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
GIT1	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.005	0.039	-10000	0	-0.46	3	3
Rac1/GTP	-0.005	0.067	-10000	0	-0.62	5	5

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.001	0.04	-9999	-0.73	1	1
PDGFB-D/PDGFRB/SLAP	-0.002	0.03	-9999	-0.63	1	1
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.025	-9999	-0.54	1	1
AKT1	0.059	0.043	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.023	0.051	-9999	-0.78	1	1
PIK3CA	0.008	0.065	-9999	-0.82	3	3
FGR	0.002	0.028	-9999	-0.56	1	1
mol:Ca2+	0.02	0.048	-9999	-0.82	1	1
MYC	0.018	0.15	-9999	-0.84	14	14
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.029	-9999	-0.45	1	1
LRP1/PDGFRB/PDGFB	-0.002	0.035	-9999	-0.54	2	2
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
GO:0007205	0.02	0.049	-9999	-0.84	1	1
PTEN	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.042	0.12	-9999	-0.31	82	82
PDGFB-D/PDGFRB/SHP2	-0.002	0.04	-9999	-0.63	2	2
PDGFB-D/PDGFRB/GRB10	-0.001	0.028	-9999	-0.63	1	1
cell cycle arrest	-0.002	0.03	-9999	-0.63	1	1
HRAS	0.012	0.021	-9999	-0.31	2	2
HIF1A	0.064	0.04	-9999	-10000	0	0
GAB1	0.013	0.064	-9999	-0.86	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.02	0.059	-9999	-0.78	1	1
PDGFB-D/PDGFRB	0.012	0.031	-9999	-0.56	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.028	-9999	-0.63	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.001	0.048	-9999	-0.75	1	1
positive regulation of MAPKKK cascade	-0.002	0.04	-9999	-0.63	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.02	0.05	-9999	-0.85	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.035	0.083	-9999	-0.79	1	1
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.18	0.28	-9999	-0.62	143	143
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.028	-9999	-0.63	1	1
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.017	0.071	-9999	-0.87	1	1
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.028	-9999	-0.63	1	1
LCK	-0.008	0.087	-9999	-0.73	6	6
PDGFRB	0.012	0.038	-9999	-0.83	1	1
ACP1	0.013	0	-9999	-10000	0	0
HCK	0.005	0.035	-9999	-0.54	1	1
ABL1	0.009	0.061	-9999	-0.83	1	1
PDGFB-D/PDGFRB/CBL	0.009	0.068	-9999	-0.95	1	1
PTPN1	0.014	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.006	0.048	-9999	-0.31	11	11
cell proliferation	0.02	0.13	-9999	-0.73	14	14
SLA	0.013	0.015	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.052	0.025	-9999	-0.43	1	1
SRC	0.005	0.028	-9999	-0.56	1	1
PI3K	-0.004	0.04	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.028	0.066	-9999	-0.69	1	1
SH2B2	0.013	0.015	-9999	-0.31	1	1
PLCgamma1/SPHK1	0.024	0.053	-9999	-0.82	1	1
LYN	0.006	0.029	-9999	-0.55	1	1
LRP1	0.012	0.038	-9999	-0.82	1	1
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.021	-9999	-0.44	1	1
SPHK1	0.006	0.05	-9999	-0.31	12	12
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.02	0.05	-9999	-0.85	1	1
PLCG1	0.02	0.051	-9999	-0.89	1	1
NHERF/PDGFRB	-0.002	0.026	-9999	-0.54	1	1
YES1	0.004	0.027	-9999	-0.55	1	1
cell migration	-0.002	0.026	-9999	-0.54	1	1
SHC/Grb2/SOS1	0	0.021	-9999	-0.44	1	1
SLC9A3R2	0.013	0	-9999	-10000	0	0
SLC9A3R1	0.012	0.021	-9999	-0.31	2	2
NHERF1-2/PDGFRB/PTEN	-0.003	0.033	-9999	-0.49	2	2
FYN	0.006	0.028	-9999	-0.55	1	1
DOK1	0.034	0.025	-9999	-0.5	1	1
HRAS/GTP	-0.001	0.014	-9999	-0.21	2	2
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.027	0.09	-9999	-0.44	14	14
PRKCD	0.034	0.025	-9999	-0.5	1	1
FER	0.031	0.049	-9999	-0.5	4	4
MAPKKK cascade	-0.001	0.02	-9999	-0.43	1	1
RASA1	0.034	0.025	-9999	-0.5	1	1
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.017	0.03	-9999	-0.45	1	1
PDGFB-D/PDGFRB/SHB	-0.001	0.028	-9999	-0.63	1	1
chemotaxis	0.01	0.059	-9999	-0.79	1	1
STAT1-3-5/STAT1-3-5	-0.003	0.023	-9999	-0.42	1	1
Bovine Papilomavirus E5/PDGFRB	0.001	0.029	-9999	-0.64	1	1
PTPRJ	0.013	0	-9999	-10000	0	0

×

p38 MAPK signaling 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
TRAF6/ASK1	-0.002	0.031	-9999	-0.39	3	3
TRAF2/ASK1	-0.001	0.025	-9999	-0.55	1	1
ATM	0.012	0.038	-9999	-0.82	1	1
MAP2K3	0.026	0.057	-9999	-0.53	2	2
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.023	0.08	-9999	-0.42	7	7
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.001	0.1	-9999	-0.66	10	10
TXN	0.009	0.006	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	-0.014	0.15	-9999	-0.82	16	16
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.028	-9999	-0.63	1	1
TAK1/TAB family	-0.001	0.014	-9999	-0.21	2	2
RAC1/OSM/MEKK3	-0.001	0.009	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.009	0.033	-9999	-0.38	2	2
TRAF6	0.007	0.03	-9999	-0.46	2	2
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.005	0.084	-9999	-0.82	5	5
CCM2	0.012	0.021	-9999	-0.31	2	2
CaM/Ca2+/CAMKIIB	-0.006	0.055	-9999	-0.55	5	5
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.006	0.063	-9999	-0.59	5	5
OSM/MEKK3	-0.001	0.013	-9999	-10000	0	0
TAOK1	-0.04	0.16	-9999	-0.46	60	60
TAOK2	0.017	0.021	-9999	-0.45	1	1
TAOK3	0.017	0.021	-9999	-0.45	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.026	-9999	-0.54	1	1
GADD45/MTK1/MTK1	-0.023	0.1	-9999	-0.49	22	22

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	0	-9999	-10000	0	0
SMAD3/SMAD4	0.049	0.02	-9999	-0.39	1	1
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.019	-9999	-0.42	1	1
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.022	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.04	0.15	-9999	-0.63	31	31
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	-0.039	0.2	-9999	-0.82	31	31
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.012	0.038	-9999	-0.82	1	1
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

Figure 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	-0.001	0.022	-9999	-0.49	1	1
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0.009	-9999	-10000	0	0
GATA1/HDAC5	0	0.009	-9999	-10000	0	0
GATA2/HDAC5	0	0.009	-9999	-10000	0	0
HDAC5/BCL6/BCoR	-0.001	0.024	-9999	-0.54	1	1
HDAC9	-0.017	0.095	-9999	-0.31	46	46
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
HDAC4/RFXANK	-0.001	0.013	-9999	-10000	0	0
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.013	0	-9999	-10000	0	0
HDAC5	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.028	-9999	-0.63	1	1
Histones	0.036	0.023	-9999	-10000	0	0
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.013	-9999	-10000	0	0
CAMK4	-0.004	0.11	-9999	-0.55	15	15
Tubulin/HDAC6	-0.006	0.054	-9999	-0.54	5	5
SUMO1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.008	0.016	-9999	-0.31	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0.032	0	-9999	-10000	0	0
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.006	0.063	-9999	-0.63	5	5
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.028	-9999	-0.63	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.01	0.067	-9999	-0.54	7	7
HDAC4/ER alpha	-0.043	0.14	-9999	-0.63	23	23
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.035	0.023	-9999	-10000	0	0
cell motility	-0.006	0.054	-9999	-0.54	5	5
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.012	0.038	-9999	-0.82	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.047	0.19	-9999	-0.52	55	55
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.012	0.038	-9999	-0.82	1	1
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.001	0.021	-9999	-0.46	1	1
GNG2	0.012	0.038	-9999	-0.82	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.005	0.084	-9999	-0.82	5	5
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.012	0.021	-9999	-0.31	2	2
nuclear import	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0.009	0.036	-9999	-0.31	6	6
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.022	0.025	-9999	-10000	0	0

×

Aurora A signaling

Figure 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
Aurora A/GADD45A	0.028	0.007	-9999	-10000	0	0
BIRC5	-0.017	0.099	-9999	-0.32	44	44
NFKBIA	0.032	0.008	-9999	-10000	0	0
CPEB1	-0.048	0.22	-9999	-0.82	36	36
AKT1	0.032	0.008	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.011	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.013	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.013	0.005	-9999	-10000	0	0
PAK1/Aurora A	0.028	0.007	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.012	0.038	-9999	-0.82	1	1
TPX2	0.002	0.068	-9999	-10000	0	0
TP53	0.031	0.006	-9999	-10000	0	0
DLG7	0.021	0.008	-9999	-10000	0	0
AURKAIP1	0.012	0.021	-9999	-0.31	2	2
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.003	0.014	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.011	-9999	-10000	0	0
AURKA	0.026	0.011	-9999	-10000	0	0
AURKB	-0.014	0.027	-9999	-10000	0	0
CDC25B	0.007	0.018	-9999	-10000	0	0
G2/M transition checkpoint	0.001	0.025	-9999	-0.5	1	1
mRNA polyadenylation	-0.034	0.13	-9999	-0.5	36	36
Aurora A/CPEB	-0.035	0.13	-9999	-0.5	36	36
Aurora A/TACC1/TRAP/chTOG	0.003	0.025	-9999	-0.46	1	1
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.028	0.007	-9999	-10000	0	0
regulation of centrosome cycle	0.002	0.01	-9999	-10000	0	0
spindle assembly	0.002	0.024	-9999	-0.46	1	1
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.01	0.037	-9999	-0.44	1	1
CENPA	-0.009	0.025	-9999	-0.26	3	3
Aurora A/PP2A	0.028	0.007	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.008	-9999	-10000	0	0
negative regulation of DNA binding	0.031	0.006	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	0.002	0.025	-9999	-0.5	1	1
mitotic prometaphase	0.006	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.011	-9999	-10000	0	0
TACC1	0.012	0.038	-9999	-0.82	1	1
TACC3	0.013	0.015	-9999	-0.31	1	1
Aurora A/Antizyme1	0.003	0.015	-9999	-10000	0	0
Aurora A/RasGAP	0.028	0.007	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.005	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.002	0.068	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.019	0.05	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.051	0.038	-10000	0	-0.44	3	3
adherens junction organization	0.04	0.038	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.053	0.056	-10000	0	-0.46	4	4
FMN1	0.019	0.11	-10000	0	-0.43	28	28
mol:IP3	-0.002	0.032	-10000	0	-0.4	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.012	-10000	0	-10000	0	0
CTNNB1	0.013	0	-10000	0	-10000	0	0
AKT1	0.049	0.035	-10000	0	-0.39	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.046	0.006	-10000	0	-10000	0	0
CTNND1	0.014	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.035	-10000	0	-0.48	2	2
VASP	0.047	0.011	-10000	0	-10000	0	0
ZYX	0.047	0.011	-10000	0	-10000	0	0
JUB	0.046	0.024	-10000	0	-0.43	1	1
EGFR(dimer)	0.042	0.047	-10000	0	-0.46	4	4
E-cadherin/beta catenin-gamma catenin	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.033	-10000	0	-0.42	3	3
PIK3CA	0.009	0.065	-10000	0	-0.82	3	3
PI3K	-0.003	0.034	-10000	0	-0.43	3	3
FYN	0.051	0.034	-10000	0	-0.35	3	3
mol:Ca2+	0.042	0.034	-10000	0	-0.4	3	3
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.002	0.032	-10000	0	-0.4	3	3
CDH1	0.013	0	-10000	0	-10000	0	0
RhoA/GDP	0.053	0.056	-10000	0	-0.74	1	1
establishment of polarity of embryonic epithelium	0.046	0.011	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.007	0.075	-10000	0	-0.82	4	4
CASR	0.042	0.037	-10000	0	-0.38	3	3
RhoA/GTP	-0.002	0.028	-10000	0	-0.36	3	3
AKT2	0.049	0.035	-10000	0	-0.39	3	3
actin cable formation	0.027	0.11	-10000	0	-0.41	28	28
apoptosis	0.003	0.032	0.41	3	-10000	0	3
CTNNA1	0.014	0.001	-10000	0	-10000	0	0
mol:GDP	0.047	0.06	-10000	0	-0.47	6	6
PIP5K1A	0.045	0.036	-10000	0	-0.5	2	2
PLCG1	-0.003	0.032	-10000	0	-0.41	3	3
Rac1/GTP	-0.004	0.038	-10000	0	-0.42	4	4
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.82	16	16
CDC42/GTP	-0.011	0.054	-9999	-10000	0	0
PLCG1	0.03	0.065	-9999	-0.33	1	1
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.011	0.053	-9999	-10000	0	0
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
MAPK3	0.03	0.065	-9999	-10000	0	0
MAPK1	0.03	0.065	-9999	-0.33	1	1
S1P/S1P5/Gi	0.022	0.071	-9999	-0.33	17	17
GNAI1	0.012	0.038	-9999	-0.82	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-9999	-0.55	1	1
RHOA	0.032	0.016	-9999	-10000	0	0
S1P/S1P4/Gi	0.023	0.068	-9999	-0.33	17	17
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.001	0.014	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.023	0.17	-10000	0	-0.73	24	24
CLTC	0.034	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.029	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0	0	-10000	0	-10000	0	0
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.031	0	-10000	0	-10000	0	0
CPE	0.012	0.068	-10000	0	-0.55	7	7
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0.028	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0	-10000	0	-10000	0	0
TSHR	0.018	0.036	-10000	0	-0.55	2	2
INS	0.013	0	-10000	0	-10000	0	0
BIN1	0.013	0	-10000	0	-10000	0	0
mol:Choline	0.028	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.031	0	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.023	-10000	0	-0.5	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.031	0	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0.015	-10000	0	-0.31	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.008	-10000	0	-10000	0	0
ACAP1	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.001	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.002	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.046	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.02	0	-10000	0	-10000	0	0
clathrin coat assembly	0.034	0	-10000	0	-10000	0	0
IL2RA	0.011	0.068	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.017	0.08	-10000	0	-0.4	20	20
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0	-10000	0	-10000	0	0
SDC1	0.03	0.009	-10000	0	-10000	0	0
ARF6/GDP	0.019	0	-10000	0	-10000	0	0
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.028	0	-10000	0	-10000	0	0
endocytosis	0.001	0.022	0.5	1	-10000	0	1
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.028	0.076	-10000	0	-0.43	13	13
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.012	0.038	-10000	0	-0.82	1	1
Dynamin 2/GDP	0.026	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.031	0.068	-10000	0	-0.43	10	10
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.032	-9999	-9999
HDAC4	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.013	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.013	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.013	-9999	-9999
SUMO1/HDAC4	0.032	-9999	-9999
SUMO1/HDAC1	0.032	-9999	-9999
RANGAP1	0.013	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.013	-9999	-9999
UBE2I	0.013	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.013	-9999	-9999
PIAS1	0.013	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

E-cadherin signaling events

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	0	-9999	-9999
E-cadherin/beta catenin	0	-9999	-9999
CTNNB1	0.013	-9999	-9999
JUP	0.013	-9999	-9999
CDH1	0.013	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.001	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.015	-9999	-0.21	2	2
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.003	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0	-9999	-10000	0	0
CD4	0.003	0.058	-9999	-0.31	16	16
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.002	0.027	-9999	-0.42	2	2
ARF1/GTP	-0.001	0.016	-9999	-0.25	2	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.002	0.027	-9999	-0.42	2	2
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	-0.002	0.027	-9999	-0.43	2	2
ARF1/GDP	0	0.007	-9999	-10000	0	0
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARFIP2	0	0.005	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.027	0.008	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	-0.001	0.009	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.029	0	-9999	-10000	0	0
ARF1/GDP/Membrin	-0.001	0.009	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.004	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.035	0.014	-9999	-10000	0	0
PLD2	-0.002	0.027	-9999	-0.42	2	2
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	-0.002	0.027	-9999	-0.43	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.001	0.015	-9999	-0.24	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.002	0.027	-9999	-0.42	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	-0.001	0.011	-9999	-0.17	2	2
USO1	-0.001	0.011	-9999	-10000	0	0
GBF1	-0.001	0.011	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.003	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.028	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.028	-9999	-0.63	1	1
RELB	0.013	0	-9999	-10000	0	0
NFKB2	0.013	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.MK.A4N9	TCGA.MK.A4N7	TCGA.MK.A4N6	TCGA.L6.A4EU
109_MAP3K5	-0.28	-0.017	-0.017	-0.017
47_PPARGC1A	-0.82	-0.82	-0.82	0.013
105_BMP4	0.013	-0.31	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	0.013	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	-0.49	-0.49	-0.49	-0.49
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.013
84_STAT5B	0.047	-0.096	0	-0.097
84_STAT5A	0.047	-0.096	0	-0.097