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

Pathway.Name	Avg.Num.Perturbations
IL23-mediated signaling events	128
Ephrin A reverse signaling	124
FOXM1 transcription factor network	97
TCGA08_retinoblastoma	93
Aurora B signaling	86
IL12-mediated signaling events	83
E-cadherin signaling events	79
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	78
Effects of Botulinum toxin	77
Signaling events mediated by the Hedgehog family	73

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
IL23-mediated signaling events	0.2495	128	7732	60	-0.67	0.014	1000	-1000	-0.13	-1000
Ephrin A reverse signaling	0.2417	124	871	7	-0.15	0	1000	-1000	-0.028	-1000
FOXM1 transcription factor network	0.1891	97	4957	51	-0.41	0.025	1000	-1000	-0.16	-1000
TCGA08_retinoblastoma	0.1813	93	747	8	-0.098	0.075	1000	-1000	-0.019	-1000
Aurora B signaling	0.1676	86	5782	67	-0.34	0.014	1000	-1000	-0.067	-1000
IL12-mediated signaling events	0.1618	83	7305	87	-0.56	0.12	1000	-1000	-0.12	-1000
E-cadherin signaling events	0.1540	79	398	5	-0.12	0.014	1000	-1000	-0.042	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1520	78	5331	68	-0.48	0.23	1000	-1000	-0.11	-1000
Effects of Botulinum toxin	0.1501	77	2022	26	-0.2	0.014	1000	-1000	-0.057	-1000
Signaling events mediated by the Hedgehog family	0.1423	73	3819	52	-0.19	0.15	1000	-1000	-0.059	-1000
TCR signaling in naïve CD8+ T cells	0.1365	70	6532	93	-0.21	0.068	1000	-1000	-0.071	-1000
Syndecan-1-mediated signaling events	0.1287	66	2266	34	-0.23	0.014	1000	-1000	-0.057	-1000
IL4-mediated signaling events	0.1209	62	5680	91	-0.61	0.44	1000	-1000	-0.14	-1000
Syndecan-4-mediated signaling events	0.1111	57	3820	67	-0.18	0.037	1000	-1000	-0.091	-1000
Glypican 2 network	0.1092	56	224	4	-0.059	-0.016	1000	-1000	-0.041	-1000
Signaling events regulated by Ret tyrosine kinase	0.1072	55	4511	82	-0.18	0.014	1000	-1000	-0.077	-1000
Thromboxane A2 receptor signaling	0.1053	54	5675	105	-0.21	0.057	1000	-1000	-0.067	-1000
Reelin signaling pathway	0.1053	54	3030	56	-0.28	0.014	1000	-1000	-0.072	-1000
Aurora C signaling	0.1033	53	372	7	-0.16	0	1000	-1000	-0.037	-1000
amb2 Integrin signaling	0.1033	53	4396	82	-0.23	0.014	1000	-1000	-0.07	-1000
a4b1 and a4b7 Integrin signaling	0.1014	52	260	5	-0.076	-0.033	1000	-1000	-0.037	-1000
Signaling mediated by p38-alpha and p38-beta	0.0994	51	2277	44	-0.15	0.014	1000	-1000	-0.052	-1000
FOXA2 and FOXA3 transcription factor networks	0.0975	50	2300	46	-0.27	0.02	1000	-1000	-0.05	-1000
Endothelins	0.0955	49	4741	96	-0.19	0.014	1000	-1000	-0.078	-1000
Caspase cascade in apoptosis	0.0936	48	3562	74	-0.19	0.043	1000	-1000	-0.052	-1000
Visual signal transduction: Cones	0.0916	47	1805	38	-0.15	0.017	1000	-1000	-0.059	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0877	45	3835	85	-0.15	0.014	1000	-1000	-0.066	-1000
Ras signaling in the CD4+ TCR pathway	0.0877	45	774	17	-0.13	0.023	1000	-1000	-0.037	-1000
HIF-1-alpha transcription factor network	0.0838	43	3310	76	-0.19	0.086	1000	-1000	-0.093	-1000
Glypican 1 network	0.0838	43	2108	48	-0.17	0.03	1000	-1000	-0.05	-1000
Calcium signaling in the CD4+ TCR pathway	0.0838	43	1335	31	-0.18	0.014	1000	-1000	-0.074	-1000
Visual signal transduction: Rods	0.0838	43	2266	52	-0.2	0.014	1000	-1000	-0.079	-1000
Arf6 signaling events	0.0819	42	2646	62	-0.2	0.014	1000	-1000	-0.054	-1000
PDGFR-alpha signaling pathway	0.0819	42	1880	44	-0.17	0.027	1000	-1000	-0.052	-1000
p75(NTR)-mediated signaling	0.0799	41	5161	125	-0.16	0.014	1000	-1000	-0.089	-1000
PLK1 signaling events	0.0760	39	3353	85	-0.17	0.041	1000	-1000	-0.042	-1000
Glucocorticoid receptor regulatory network	0.0760	39	4522	114	-0.43	0.23	1000	-1000	-0.061	-1000
PLK2 and PLK4 events	0.0741	38	115	3	-0.018	-0.013	1000	-1000	-0.016	-1000
Osteopontin-mediated events	0.0741	38	1465	38	-0.13	0.016	1000	-1000	-0.09	-1000
IL1-mediated signaling events	0.0741	38	2356	62	-0.19	0.064	1000	-1000	-0.089	-1000
Nongenotropic Androgen signaling	0.0721	37	1969	52	-0.11	0.037	1000	-1000	-0.051	-1000
LPA receptor mediated events	0.0721	37	3850	102	-0.18	0.019	1000	-1000	-0.075	-1000
BCR signaling pathway	0.0721	37	3687	99	-0.17	0.03	1000	-1000	-0.083	-1000
EGFR-dependent Endothelin signaling events	0.0721	37	783	21	-0.11	0.014	1000	-1000	-0.06	-1000
Wnt signaling	0.0702	36	254	7	-0.034	-0.013	1000	-1000	-0.017	-1000
TCGA08_p53	0.0663	34	242	7	-0.074	0.049	1000	-1000	-0.015	-1000
IL6-mediated signaling events	0.0643	33	2534	75	-0.15	0.064	1000	-1000	-0.074	-1000
BMP receptor signaling	0.0624	32	2662	81	-0.17	0.05	1000	-1000	-0.085	-1000
Fc-epsilon receptor I signaling in mast cells	0.0624	32	3129	97	-0.19	0.04	1000	-1000	-0.08	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0624	32	1684	52	-0.19	0.027	1000	-1000	-0.049	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0624	32	2868	88	-0.18	0.019	1000	-1000	-0.11	-1000
Coregulation of Androgen receptor activity	0.0604	31	2358	76	-0.14	0.027	1000	-1000	-0.041	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0604	31	1181	37	-0.13	0.014	1000	-1000	-0.053	-1000
ErbB2/ErbB3 signaling events	0.0585	30	1989	65	-0.17	0.023	1000	-1000	-0.058	-1000
Retinoic acid receptors-mediated signaling	0.0585	30	1754	58	-0.19	0.016	1000	-1000	-0.072	-1000
Rapid glucocorticoid signaling	0.0585	30	614	20	-0.17	0.014	1000	-1000	-0.038	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0565	29	3545	120	-0.21	0.13	1000	-1000	-0.07	-1000
Syndecan-2-mediated signaling events	0.0546	28	1991	69	-0.16	0.034	1000	-1000	-0.05	-1000
FAS signaling pathway (CD95)	0.0546	28	1325	47	-0.15	0.016	1000	-1000	-0.042	-1000
LPA4-mediated signaling events	0.0526	27	324	12	-0.052	0.014	1000	-1000	-0.02	-1000
Regulation of nuclear SMAD2/3 signaling	0.0526	27	3703	136	-0.22	0.22	1000	-1000	-0.066	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0526	27	1482	54	-0.16	0.029	1000	-1000	-0.087	-1000
Presenilin action in Notch and Wnt signaling	0.0526	27	1676	61	-0.28	0.03	1000	-1000	-0.069	-1000
IL2 signaling events mediated by STAT5	0.0526	27	607	22	-0.093	0.019	1000	-1000	-0.04	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0507	26	885	34	-0.062	0.014	1000	-1000	-0.063	-1000
Noncanonical Wnt signaling pathway	0.0507	26	683	26	-0.11	0.014	1000	-1000	-0.05	-1000
JNK signaling in the CD4+ TCR pathway	0.0487	25	427	17	-0.071	0.014	1000	-1000	-0.056	-1000
Signaling events mediated by HDAC Class III	0.0487	25	1025	40	-0.12	0.1	1000	-1000	-0.042	-1000
Syndecan-3-mediated signaling events	0.0487	25	903	35	-0.16	0.014	1000	-1000	-0.055	-1000
Canonical Wnt signaling pathway	0.0468	24	1256	51	-0.28	0.096	1000	-1000	-0.049	-1000
E-cadherin signaling in the nascent adherens junction	0.0468	24	1848	76	-0.12	0.014	1000	-1000	-0.076	-1000
Cellular roles of Anthrax toxin	0.0448	23	932	39	-0.16	0.019	1000	-1000	-0.026	-1000
IL2 signaling events mediated by PI3K	0.0448	23	1375	58	-0.093	0.032	1000	-1000	-0.074	-1000
IL27-mediated signaling events	0.0448	23	1201	51	-0.16	0.019	1000	-1000	-0.087	-1000
Signaling events mediated by PTP1B	0.0429	22	1722	76	-0.14	0.02	1000	-1000	-0.074	-1000
Ceramide signaling pathway	0.0429	22	1716	76	-0.15	0.022	1000	-1000	-0.055	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0409	21	1556	74	-0.16	0.064	1000	-1000	-0.085	-1000
ErbB4 signaling events	0.0390	20	1442	69	-0.15	0.041	1000	-1000	-0.076	-1000
TCGA08_rtk_signaling	0.0390	20	540	26	-0.15	0.028	1000	-1000	-0.018	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0390	20	1634	78	-0.062	0.04	1000	-1000	-0.06	-1000
S1P1 pathway	0.0370	19	707	36	-0.1	0.014	1000	-1000	-0.054	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0351	18	507	28	-0.13	0.024	1000	-1000	-0.039	-1000
S1P5 pathway	0.0351	18	318	17	-0.13	0.052	1000	-1000	-0.039	-1000
Ephrin B reverse signaling	0.0351	18	911	48	-0.1	0.076	1000	-1000	-0.063	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0351	18	1508	83	-0.19	0.053	1000	-1000	-0.068	-1000
Aurora A signaling	0.0331	17	1068	60	-0.14	0.032	1000	-1000	-0.059	-1000
Integrins in angiogenesis	0.0331	17	1465	84	-0.094	0.014	1000	-1000	-0.088	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0331	17	785	45	-0.15	0.031	1000	-1000	-0.083	-1000
Insulin-mediated glucose transport	0.0312	16	522	32	-0.11	0.034	1000	-1000	-0.054	-1000
TRAIL signaling pathway	0.0312	16	795	48	-0.047	0.029	1000	-1000	-0.065	-1000
EPHB forward signaling	0.0312	16	1380	85	-0.1	0.035	1000	-1000	-0.081	-1000
Regulation of Telomerase	0.0312	16	1685	102	-0.14	0.045	1000	-1000	-0.092	-1000
E-cadherin signaling in keratinocytes	0.0312	16	701	43	-0.12	0.026	1000	-1000	-0.064	-1000
Signaling mediated by p38-gamma and p38-delta	0.0292	15	236	15	-0.027	0.026	1000	-1000	-0.025	-1000
BARD1 signaling events	0.0273	14	804	57	-0.052	0.029	1000	-1000	-0.061	-1000
Regulation of p38-alpha and p38-beta	0.0273	14	788	54	-0.12	0.014	1000	-1000	-0.057	-1000
Plasma membrane estrogen receptor signaling	0.0273	14	1219	86	-0.056	0.033	1000	-1000	-0.077	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0273	14	466	33	-0.1	0.041	1000	-1000	-0.056	-1000
Regulation of Androgen receptor activity	0.0273	14	987	70	-0.13	0.032	1000	-1000	-0.068	-1000
ceramide signaling pathway	0.0253	13	676	49	-0.15	0.02	1000	-1000	-0.04	-1000
Paxillin-dependent events mediated by a4b1	0.0253	13	484	36	-0.13	0.03	1000	-1000	-0.069	-1000
S1P4 pathway	0.0253	13	341	25	-0.13	0.03	1000	-1000	-0.051	-1000
EPO signaling pathway	0.0234	12	680	55	-0.11	0.057	1000	-1000	-0.082	-1000
p38 MAPK signaling pathway	0.0234	12	553	44	-0.071	0.02	1000	-1000	-0.063	-1000
Nectin adhesion pathway	0.0214	11	726	63	-0.12	0.048	1000	-1000	-0.071	-1000
Canonical NF-kappaB pathway	0.0195	10	404	39	-0.15	0.086	1000	-1000	-0.081	-1000
IFN-gamma pathway	0.0195	10	717	68	-0.23	0.058	1000	-1000	-0.083	-1000
Class I PI3K signaling events	0.0195	10	785	73	-0.11	0.03	1000	-1000	-0.06	-1000
Signaling events mediated by PRL	0.0195	10	351	34	-0.064	0.021	1000	-1000	-0.039	-1000
Circadian rhythm pathway	0.0175	9	206	22	-0.018	0.033	1000	-1000	-0.047	-1000
Signaling events mediated by HDAC Class I	0.0175	9	1007	104	-0.15	0.058	1000	-1000	-0.057	-1000
Class IB PI3K non-lipid kinase events	0.0175	9	27	3	-0.004	0.004	1000	-1000	-0.017	-1000
HIF-2-alpha transcription factor network	0.0156	8	352	43	-0.097	0.098	1000	-1000	-0.076	-1000
Atypical NF-kappaB pathway	0.0156	8	260	31	-0.081	0.029	1000	-1000	-0.039	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0156	8	1055	125	-0.073	0.075	1000	-1000	-0.096	-1000
Insulin Pathway	0.0136	7	542	74	-0.18	0.038	1000	-1000	-0.082	-1000
VEGFR1 specific signals	0.0136	7	419	56	-0.092	0.04	1000	-1000	-0.073	-1000
S1P3 pathway	0.0136	7	330	42	-0.033	0.031	1000	-1000	-0.042	-1000
Signaling events mediated by HDAC Class II	0.0117	6	500	75	-0.17	0.038	1000	-1000	-0.057	-1000
Hedgehog signaling events mediated by Gli proteins	0.0117	6	434	65	-0.043	0.064	1000	-1000	-0.061	-1000
PDGFR-beta signaling pathway	0.0117	6	617	97	-0.055	0.063	1000	-1000	-0.08	-1000
FoxO family signaling	0.0097	5	350	64	-0.11	0.12	1000	-1000	-0.065	-1000
Arf6 trafficking events	0.0097	5	366	71	-0.11	0.047	1000	-1000	-0.072	-1000
IGF1 pathway	0.0097	5	311	57	-0.048	0.053	1000	-1000	-0.086	-1000
Arf6 downstream pathway	0.0078	4	212	43	-0.027	0.028	1000	-1000	-0.033	-1000
Class I PI3K signaling events mediated by Akt	0.0078	4	335	68	-0.11	0.054	1000	-1000	-0.054	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0039	2	51	23	-0.014	0.05	1000	-1000	-0.061	-1000
Alternative NF-kappaB pathway	0.0039	2	28	13	-0.005	0.014	1000	-1000	-0.052	-1000
mTOR signaling pathway	0.0019	1	87	53	-0.005	0.036	1000	-1000	-0.056	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	20	27	-0.004	0.036	1000	-1000	-0.053	-1000
Arf1 pathway	0.0000	0	25	54	-0.003	0.037	1000	-1000	-0.04	-1000
Total	NA	4033	221000	7203	-20	5.5	131000	-131000	-8.2	-131000

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.58	0.56	-10000	0	-1.2	208	208
IL23A	-0.6	0.56	-10000	0	-1.2	206	206
NF kappa B1 p50/RelA/I kappa B alpha	-0.57	0.51	-10000	0	-1.1	208	208
positive regulation of T cell mediated cytotoxicity	-0.62	0.61	-10000	0	-1.2	212	212
ITGA3	-0.55	0.52	-10000	0	-1.1	176	176
IL17F	-0.35	0.33	-10000	0	-0.71	181	181
IL12B	-0.024	0.064	-10000	0	-0.54	6	6
STAT1 (dimer)	-0.6	0.58	-10000	0	-1.2	213	213
CD4	-0.53	0.5	-10000	0	-1.1	192	192
IL23	-0.58	0.53	-10000	0	-1.1	207	207
IL23R	-0.082	0.084	-10000	0	-0.51	1	1
IL1B	-0.64	0.61	-10000	0	-1.2	220	220
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.53	0.5	-10000	0	-1.1	190	190
TYK2	-0.001	0.018	-10000	0	-10000	0	0
STAT4	-0.16	0.26	-10000	0	-0.53	161	161
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.077	0.21	-10000	0	-0.54	85	85
IL12RB1	-0.049	0.16	-10000	0	-0.59	42	42
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL12Rbeta1/TYK2	-0.039	0.12	-10000	0	-0.44	42	42
IL23R/JAK2	-0.093	0.1	-10000	0	-0.5	1	1
positive regulation of chronic inflammatory response	-0.62	0.61	-10000	0	-1.2	212	212
natural killer cell activation	0.008	0.007	0.047	1	-10000	0	1
JAK2	0.008	0.018	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
NFKB1	0.011	0.003	-10000	0	-10000	0	0
RELA	0.011	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.55	0.49	-10000	0	-1.1	207	207
ALOX12B	-0.6	0.56	-10000	0	-1.2	211	211
CXCL1	-0.59	0.55	-10000	0	-1.2	213	213
T cell proliferation	-0.62	0.61	-10000	0	-1.2	212	212
NFKBIA	0.011	0.003	-10000	0	-10000	0	0
IL17A	-0.26	0.26	-10000	0	-0.57	142	142
PI3K	-0.58	0.52	-10000	0	-1.1	212	212
IFNG	-0.023	0.031	-10000	0	-0.099	17	17
STAT3 (dimer)	-0.55	0.48	-10000	0	-1.1	206	206
IL18R1	-0.049	0.18	-10000	0	-0.54	60	60
IL23/IL23R/JAK2/TYK2/SOCS3	-0.32	0.3	-10000	0	-0.64	173	173
IL18/IL18R	-0.093	0.21	-10000	0	-0.4	135	135
macrophage activation	-0.027	0.018	-10000	0	-0.044	208	208
TNF	-0.63	0.6	-10000	0	-1.3	209	209
STAT3/STAT4	-0.64	0.53	-10000	0	-1.1	245	245
STAT4 (dimer)	-0.66	0.59	-10000	0	-1.2	235	235
IL18	-0.029	0.15	-10000	0	-0.54	41	41
IL19	-0.53	0.5	-10000	0	-1.1	190	190
STAT5A (dimer)	-0.6	0.58	-10000	0	-1.2	209	209
STAT1	-0.002	0.088	-10000	0	-0.49	16	16
SOCS3	-0.11	0.23	-10000	0	-0.52	124	124
CXCL9	-0.62	0.56	-10000	0	-1.2	217	217
MPO	-0.62	0.56	-10000	0	-1.2	224	224
positive regulation of humoral immune response	-0.62	0.61	-10000	0	-1.2	212	212
IL23/IL23R/JAK2/TYK2	-0.67	0.71	-10000	0	-1.4	211	211
IL6	-0.6	0.56	-10000	0	-1.2	205	205
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
IL2	0.006	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.007	0.047	1	-10000	0	1
CD3E	-0.61	0.56	-10000	0	-1.2	216	216
keratinocyte proliferation	-0.62	0.61	-10000	0	-1.2	212	212
NOS2	-0.55	0.53	-10000	0	-1.1	193	193

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.14	0.22	-9999	-0.44	171	171
EFNA5	-0.084	0.21	-9999	-0.54	90	90
FYN	-0.11	0.21	-9999	-0.44	128	128
neuron projection morphogenesis	-0.14	0.22	-9999	-0.44	171	171
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.15	0.22	-9999	-0.44	171	171
EPHA5	-0.14	0.25	-9999	-0.55	140	140

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.21	0.64	-10000	0	-1.2	127	127
PLK1	-0.003	0.19	-10000	0	-1.5	4	4
BIRC5	-0.22	0.54	-10000	0	-1.5	74	74
HSPA1B	-0.23	0.66	-10000	0	-1.2	132	132
MAP2K1	0.023	0.051	-10000	0	-0.54	1	1
BRCA2	-0.23	0.68	-10000	0	-1.2	138	138
FOXM1	-0.37	0.93	-10000	0	-1.7	136	136
XRCC1	-0.21	0.64	-10000	0	-1.2	124	124
FOXM1B/p19	-0.38	0.56	0.43	6	-1.3	134	140
Cyclin D1/CDK4	-0.2	0.6	-10000	0	-1.1	130	130
CDC2	-0.23	0.68	-10000	0	-1.3	135	135
TGFA	-0.18	0.58	-10000	0	-1	133	133
SKP2	-0.22	0.65	-10000	0	-1.2	130	130
CCNE1	0.012	0.041	-10000	0	-0.5	3	3
CKS1B	-0.21	0.64	-10000	0	-1.2	127	127
RB1	-0.17	0.27	-10000	0	-0.74	64	64
FOXM1C/SP1	-0.29	0.76	-10000	0	-1.4	136	136
AURKB	-0.27	0.58	-10000	0	-1.5	92	92
CENPF	-0.24	0.7	-10000	0	-1.3	131	131
CDK4	0.002	0.092	-10000	0	-0.5	16	16
MYC	-0.18	0.57	-10000	0	-1	130	130
CHEK2	0.007	0.11	-10000	0	-0.56	16	16
ONECUT1	-0.22	0.64	-10000	0	-1.2	135	135
CDKN2A	-0.1	0.23	-10000	0	-0.56	104	104
LAMA4	-0.21	0.65	-10000	0	-1.2	131	131
FOXM1B/HNF6	-0.31	0.78	-10000	0	-1.5	137	137
FOS	-0.3	0.7	-10000	0	-1.2	172	172
SP1	0.014	0.006	-10000	0	-10000	0	0
CDC25B	-0.21	0.64	-10000	0	-1.2	127	127
response to radiation	0.008	0.041	-10000	0	-10000	0	0
CENPB	-0.21	0.64	-10000	0	-1.2	127	127
CENPA	-0.26	0.71	-10000	0	-1.3	138	138
NEK2	-0.28	0.72	-10000	0	-1.3	144	144
HIST1H2BA	-0.22	0.64	-10000	0	-1.2	130	130
CCNA2	-0.055	0.19	-10000	0	-0.54	66	66
EP300	0.009	0.053	-10000	0	-0.59	4	4
CCNB1/CDK1	-0.29	0.78	-10000	0	-1.5	130	130
CCNB2	-0.28	0.73	-10000	0	-1.4	144	144
CCNB1	-0.24	0.69	-10000	0	-1.3	131	131
ETV5	-0.23	0.65	-10000	0	-1.2	134	134
ESR1	-0.23	0.66	-10000	0	-1.2	137	137
CCND1	-0.2	0.62	-10000	0	-1.1	133	133
GSK3A	0.025	0.036	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.015	0.16	-10000	0	-0.39	69	69
CDK2	0.001	0.089	-10000	0	-0.54	13	13
G2/M transition of mitotic cell cycle	0.008	0.049	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.41	0.58	-10000	0	-1.3	141	141
GAS1	-0.22	0.65	-10000	0	-1.2	130	130
MMP2	-0.22	0.66	-10000	0	-1.2	128	128
RB1/FOXM1C	-0.22	0.64	-10000	0	-1.2	133	133
CREBBP	0.014	0	-10000	0	-10000	0	0

×

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	-0.059	0.19	-10000	0	-0.54	68	68
CDKN2C	-0.022	0.13	-10000	0	-0.44	46	46
CDKN2A	-0.098	0.22	-10000	0	-0.53	104	104
CCND2	0.064	0.14	0.31	101	-0.14	2	103
RB1	-0.068	0.15	-10000	0	-0.33	101	101
CDK4	0.075	0.15	0.33	107	-10000	0	107
CDK6	0.068	0.15	0.34	102	-0.16	15	117
G1/S progression	0.055	0.15	0.32	101	-10000	0	101

×

Aurora B signaling

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
Condensin I complex	-0.13	0.26	-9999	-0.54	127	127
STMN1	-0.1	0.2	-9999	-0.4	157	157
Aurora B/RasGAP/Survivin	-0.17	0.28	-9999	-0.55	170	170
Chromosomal passenger complex/Cul3 protein complex	-0.092	0.2	-9999	-0.4	128	128
BIRC5	-0.14	0.26	-9999	-0.57	137	137
DES	-0.34	0.45	-9999	-0.92	167	167
Aurora C/Aurora B/INCENP	-0.1	0.17	-9999	-0.32	175	175
Aurora B/TACC1	-0.094	0.16	-9999	-0.33	156	156
Aurora B/PP2A	-0.11	0.19	-9999	-0.4	156	156
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.029	0.074	-9999	-0.17	93	93
mitotic metaphase/anaphase transition	0	0.006	-9999	-10000	0	0
NDC80	-0.19	0.32	-9999	-0.6	180	180
Cul3 protein complex	-0.008	0.052	-9999	-0.36	11	11
KIF2C	-0.13	0.28	-9999	-0.44	168	168
PEBP1	0.005	0.055	-9999	-0.61	4	4
KIF20A	-0.17	0.27	-9999	-0.55	168	168
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.11	0.19	-9999	-0.4	156	156
SEPT1	0.009	0.052	-9999	-0.51	5	5
SMC2	0.014	0	-9999	-10000	0	0
SMC4	-0.016	0.12	-9999	-0.49	31	31
NSUN2/NPM1/Nucleolin	-0.16	0.33	-9999	-0.83	92	92
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.076	0.15	-9999	-0.29	156	156
AURKB	-0.16	0.27	-9999	-0.56	156	156
AURKC	-0.022	0.14	-9999	-0.52	35	35
CDCA8	-0.062	0.18	-9999	-0.53	69	69
cytokinesis	-0.27	0.4	-9999	-0.79	168	168
Aurora B/Septin1	-0.24	0.38	-9999	-0.75	166	166
AURKA	-0.015	0.12	-9999	-0.5	29	29
INCENP	0.008	0.029	-9999	-0.62	1	1
KLHL13	0.012	0.038	-9999	-0.59	2	2
BUB1	-0.11	0.24	-9999	-0.55	117	117
hSgo1/Aurora B/Survivin	-0.23	0.35	-9999	-0.67	181	181
EVI5	0.013	0.003	-9999	-10000	0	0
RhoA/GTP	-0.24	0.35	-9999	-0.71	163	163
SGOL1	-0.12	0.24	-9999	-0.54	126	126
CENPA	-0.17	0.32	-9999	-0.57	165	165
NCAPG	-0.14	0.25	-9999	-0.55	141	141
Aurora B/HC8 Proteasome	-0.11	0.19	-9999	-0.4	156	156
NCAPD2	0.009	0.05	-9999	-0.49	5	5
Aurora B/PP1-gamma	-0.11	0.19	-9999	-0.4	156	156
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	-0.065	0.19	-9999	-0.54	74	74
NPM1	-0.13	0.24	-9999	-0.61	92	92
RASA1	0.014	0	-9999	-10000	0	0
KLHL9	0.004	0.08	-9999	-0.59	9	9
mitotic prometaphase	-0.006	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.11	0.19	-9999	-0.39	156	156
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.26	0.39	-9999	-0.77	169	169
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.13	0.24	-9999	-0.61	92	92
MYLK	-0.086	0.16	-9999	-0.3	165	165
KIF23	-0.11	0.23	-9999	-0.54	113	113
VIM	-0.16	0.24	-9999	-0.43	213	213
RACGAP1	0.004	0.057	-9999	-0.52	6	6
mitosis	0	0	-9999	-10000	0	0
NCL	-0.13	0.24	-9999	-0.61	92	92
Chromosomal passenger complex	-0.21	0.38	-9999	-0.69	166	166
Chromosomal passenger complex/EVI5	-0.18	0.31	-9999	-0.6	162	162
TACC1	0.014	0	-9999	-10000	0	0
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.12	0.17	-10000	0	-0.39	99	99
TBX21	-0.47	0.5	-10000	0	-1.1	177	177
B2M	0.009	0.05	-10000	0	-0.5	5	5
TYK2	0.001	0.019	-10000	0	-10000	0	0
IL12RB1	-0.046	0.16	-10000	0	-0.58	42	42
GADD45B	-0.35	0.39	-10000	0	-0.88	122	122
IL12RB2	-0.13	0.23	-10000	0	-0.54	123	123
GADD45G	-0.37	0.41	-10000	0	-0.96	114	114
natural killer cell activation	-0.016	0.023	-10000	0	-10000	0	0
RELB	0.009	0.052	-10000	0	-0.51	5	5
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.034	0.16	-10000	0	-0.56	41	41
IL2RA	-0.062	0.18	-10000	0	-0.5	71	71
IFNG	-0.002	0.049	-10000	0	-0.49	5	5
STAT3 (dimer)	-0.36	0.36	-10000	0	-0.76	185	185
HLA-DRB5	-0.13	0.24	-10000	0	-0.54	129	129
FASLG	-0.44	0.47	-10000	0	-1	170	170
NF kappa B2 p52/RelB	-0.46	0.43	-10000	0	-0.93	198	198
CD4	0.006	0.056	-10000	0	-0.51	6	6
SOCS1	-0.032	0.15	-10000	0	-0.51	45	45
EntrezGene:6955	-0.002	0.008	-10000	0	-10000	0	0
CD3D	-0.11	0.23	-10000	0	-0.53	117	117
CD3E	-0.13	0.24	-10000	0	-0.54	136	136
CD3G	-0.035	0.14	-10000	0	-0.5	43	43
IL12Rbeta2/JAK2	-0.095	0.18	-10000	0	-0.4	123	123
CCL3	-0.56	0.58	-10000	0	-1.2	207	207
CCL4	-0.56	0.59	-10000	0	-1.2	189	189
HLA-A	0.005	0.07	-10000	0	-0.49	10	10
IL18/IL18R	-0.091	0.22	-10000	0	-0.42	141	141
NOS2	-0.41	0.45	-10000	0	-0.96	159	159
IL12/IL12R/TYK2/JAK2/SPHK2	-0.1	0.15	-10000	0	-0.39	73	73
IL1R1	-0.45	0.48	-10000	0	-1.1	158	158
IL4	0.019	0.023	-10000	0	-10000	0	0
JAK2	0.001	0.019	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.12	0.23	-10000	0	-0.55	87	87
RAB7A	-0.28	0.32	-10000	0	-0.76	89	89
lysosomal transport	-0.27	0.3	-10000	0	-0.71	90	90
FOS	-0.36	0.46	-10000	0	-0.96	143	143
STAT4 (dimer)	-0.42	0.41	-10000	0	-0.88	185	185
STAT5A (dimer)	-0.47	0.44	-10000	0	-0.94	199	199
GZMA	-0.52	0.54	-10000	0	-1.1	182	182
GZMB	-0.5	0.53	-10000	0	-1.1	190	190
HLX	-0.002	0.092	-10000	0	-0.52	16	16
LCK	-0.51	0.53	-10000	0	-1	212	212
TCR/CD3/MHC II/CD4	-0.16	0.24	-10000	0	-0.5	143	143
IL2/IL2R	-0.12	0.21	-10000	0	-0.48	102	102
MAPK14	-0.35	0.39	-10000	0	-0.85	141	141
CCR5	-0.41	0.46	-10000	0	-0.98	144	144
IL1B	-0.19	0.27	-10000	0	-0.56	173	173
STAT6	-0.11	0.12	-10000	0	-0.36	2	2
STAT4	-0.16	0.26	-10000	0	-0.53	161	161
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.002	0.088	-10000	0	-0.49	16	16
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.011	0.044	-10000	0	-0.56	3	3
IL12B	-0.016	0.06	-10000	0	-0.53	6	6
CD8A	-0.076	0.21	-10000	0	-0.55	83	83
CD8B	-0.031	0.16	-10000	0	-0.56	41	41
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.12	0.17	0.38	99	-10000	0	99
IL2RB	-0.094	0.22	-10000	0	-0.53	102	102
proteasomal ubiquitin-dependent protein catabolic process	-0.38	0.37	-10000	0	-0.79	183	183
IL2RG	-0.042	0.16	-10000	0	-0.52	54	54
IL12	-0.035	0.11	-10000	0	-0.44	35	35
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
CD247	-0.02	0.13	-10000	0	-0.52	31	31
IL2	0.001	0.003	-10000	0	-10000	0	0
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.033	0.14	-10000	0	-0.6	29	29
IL12/IL12R/TYK2/JAK2	-0.52	0.58	-10000	0	-1.1	198	198
MAP2K3	-0.36	0.4	-10000	0	-0.82	161	161
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.36	0.4	-10000	0	-0.85	148	148
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.091	0.22	-10000	0	-0.54	97	97
IL18RAP	-0.082	0.21	-10000	0	-0.55	85	85
IL12Rbeta1/TYK2	-0.035	0.12	-10000	0	-0.43	42	42
EOMES	-0.002	0.13	-10000	0	-1.3	1	1
STAT1 (dimer)	-0.36	0.35	-10000	0	-0.76	177	177
T cell proliferation	-0.31	0.29	-10000	0	-0.64	171	171
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.054	0.18	-10000	0	-0.55	60	60
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.29	-10000	0	-0.69	188	188
ATF2	-0.33	0.36	-10000	0	-0.8	132	132

×

E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.085	0.15	-9999	-0.32	134	134
E-cadherin/beta catenin	-0.095	0.17	-9999	-0.38	127	127
CTNNB1	0.014	0	-9999	-10000	0	0
JUP	0.003	0.081	-9999	-0.57	10	10
CDH1	-0.12	0.24	-9999	-0.54	127	127

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.013	0.1	-10000	0	-0.57	12	12
NFATC2	-0.13	0.3	-10000	0	-0.74	76	76
NFATC3	-0.049	0.11	-10000	0	-0.3	14	14
CD40LG	-0.38	0.49	-10000	0	-1	159	159
ITCH	-0.031	0.12	-10000	0	-0.52	3	3
CBLB	-0.032	0.13	-10000	0	-0.6	4	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.33	0.41	-10000	0	-0.96	111	111
JUNB	-0.033	0.15	-10000	0	-0.51	46	46
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.084	0.12	-10000	0	-0.3	89	89
T cell anergy	-0.095	0.19	-10000	0	-0.42	99	99
TLE4	-0.081	0.25	-10000	0	-0.71	46	46
Jun/NFAT1-c-4/p21SNFT	-0.36	0.46	-10000	0	-1	139	139
AP-1/NFAT1-c-4	-0.46	0.6	-10000	0	-1.3	152	152
IKZF1	-0.093	0.28	-10000	0	-0.78	51	51
T-helper 2 cell differentiation	-0.18	0.3	-10000	0	-0.86	50	50
AP-1/NFAT1	-0.17	0.26	-10000	0	-0.57	116	116
CALM1	-0.026	0.088	-10000	0	-0.55	3	3
EGR2	-0.31	0.56	-10000	0	-1.3	101	101
EGR3	-0.34	0.6	-10000	0	-1.2	131	131
NFAT1/FOXP3	-0.12	0.25	-10000	0	-0.63	72	72
EGR1	-0.11	0.23	-10000	0	-0.54	115	115
JUN	-0.003	0.078	-10000	0	-0.51	11	11
EGR4	-0.19	0.27	-10000	0	-0.55	184	184
mol:Ca2+	-0.041	0.083	-10000	0	-0.3	1	1
GBP3	-0.16	0.35	-10000	0	-0.82	92	92
FOSL1	-0.093	0.22	-10000	0	-0.53	101	101
NFAT1-c-4/MAF/IRF4	-0.33	0.45	-10000	0	-0.99	128	128
DGKA	-0.074	0.23	-10000	0	-0.64	46	46
CREM	0.012	0.035	-10000	0	-0.54	2	2
NFAT1-c-4/PPARG	-0.34	0.46	-10000	0	-1	132	132
CTLA4	-0.12	0.29	-10000	0	-0.68	89	89
NFAT1-c-4 (dimer)/EGR1	-0.39	0.53	-10000	0	-1.1	146	146
NFAT1-c-4 (dimer)/EGR4	-0.43	0.49	-10000	0	-1	162	162
FOS	-0.1	0.22	-10000	0	-0.56	99	99
IFNG	-0.17	0.24	-10000	0	-0.75	48	48
T cell activation	-0.17	0.29	-10000	0	-0.76	56	56
MAF	0.011	0.046	-10000	0	-0.59	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.23	0.42	0.88	112	-10000	0	112
TNF	-0.48	0.51	-10000	0	-1	202	202
FASLG	-0.35	0.57	-10000	0	-1.3	111	111
TBX21	-0.045	0.17	-10000	0	-0.53	56	56
BATF3	-0.035	0.16	-10000	0	-0.53	46	46
PRKCQ	-0.005	0.11	-10000	0	-0.58	17	17
PTPN1	-0.074	0.23	-10000	0	-0.65	45	45
NFAT1-c-4/ICER1	-0.32	0.46	-10000	0	-0.99	131	131
GATA3	-0.11	0.23	-10000	0	-0.54	115	115
T-helper 1 cell differentiation	-0.16	0.25	-10000	0	-0.73	48	48
IL2RA	-0.3	0.34	-10000	0	-0.83	108	108
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.075	0.23	-10000	0	-0.6	56	56
E2F1	-0.01	0.12	-10000	0	-0.52	28	28
PPARG	-0.014	0.12	-10000	0	-0.56	25	25
SLC3A2	-0.074	0.23	-10000	0	-0.63	48	48
IRF4	-0.042	0.17	-10000	0	-0.54	52	52
PTGS2	-0.41	0.53	-10000	0	-1.1	159	159
CSF2	-0.37	0.48	-10000	0	-1	146	146
JunB/Fra1/NFAT1-c-4	-0.37	0.47	-10000	0	-1	145	145
IL4	-0.19	0.31	-10000	0	-0.93	47	47
IL5	-0.36	0.48	-10000	0	-1	147	147
IL2	-0.17	0.29	-10000	0	-0.77	55	55
IL3	-0.063	0.06	-10000	0	-10000	0	0
RNF128	-0.15	0.29	-10000	0	-0.55	170	170
NFATC1	-0.23	0.43	-10000	0	-0.89	111	111
CDK4	0.13	0.25	0.67	28	-0.6	1	29
PTPRK	-0.076	0.23	-10000	0	-0.6	61	61
IL8	-0.43	0.53	-10000	0	-1.1	172	172
POU2F1	0.014	0.001	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.048	0.14	-9999	-0.36	83	83
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.093	0.17	-9999	-0.4	120	120
STXBP1	-0.014	0.12	-9999	-0.5	28	28
ACh/CHRNA1	-0.13	0.17	-9999	-0.37	161	161
RAB3GAP2/RIMS1/UNC13B	-0.077	0.14	-9999	-0.33	120	120
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	-0.12	0.24	-9999	-0.55	120	120
mol:ACh	-0.037	0.068	-9999	-0.13	163	163
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.14	0.2	-9999	-0.45	128	128
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.13	0.17	-9999	-0.37	161	161
UNC13B	0.013	0.027	-9999	-0.59	1	1
CHRNA1	-0.16	0.26	-9999	-0.53	161	161
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.15	0.21	-9999	-0.41	198	198
SNAP25	-0.074	0.13	-9999	-0.25	166	166
VAMP2	0.007	0.007	-9999	-0.14	1	1
SYT1	-0.2	0.27	-9999	-0.54	198	198
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.046	0.16	-9999	-0.38	85	85
STX1A/SNAP25 fragment 1/VAMP2	-0.14	0.2	-9999	-0.45	128	128

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.1	0.29	-10000	0	-0.72	65	65
IHH	-0.014	0.086	-10000	0	-0.51	9	9
SHH Np/Cholesterol/GAS1	-0.069	0.16	-10000	0	-0.32	143	143
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.086	0.15	0.31	143	-10000	0	143
SMO/beta Arrestin2	-0.036	0.18	-10000	0	-0.58	24	24
SMO	-0.046	0.18	-10000	0	-0.53	37	37
AKT1	0.002	0.083	-10000	0	-0.31	6	6
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	0.007	0.062	-10000	0	-0.56	6	6
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.045	0.18	-10000	0	-0.52	37	37
STIL	-0.093	0.22	-10000	0	-0.52	74	74
DHH N/PTCH2	-0.058	0.14	-10000	0	-0.4	73	73
DHH N/PTCH1	-0.069	0.19	-10000	0	-0.54	39	39
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
DHH	-0.046	0.17	-10000	0	-0.54	55	55
PTHLH	-0.12	0.34	-10000	0	-0.92	63	63
determination of left/right symmetry	-0.045	0.18	-10000	0	-0.52	37	37
PIK3R1	0.014	0	-10000	0	-10000	0	0
skeletal system development	-0.11	0.34	-10000	0	-0.91	63	63
IHH N/Hhip	-0.12	0.21	-10000	0	-0.45	141	141
DHH N/Hhip	-0.15	0.21	-10000	0	-0.42	178	178
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.045	0.18	-10000	0	-0.52	37	37
pancreas development	-0.14	0.25	-10000	0	-0.55	140	140
HHAT	-0.006	0.11	-10000	0	-0.57	18	18
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.014	0.12	-10000	0	-0.5	28	28
somite specification	-0.045	0.18	-10000	0	-0.52	37	37
SHH Np/Cholesterol/PTCH1	-0.093	0.21	-10000	0	-0.52	69	69
SHH Np/Cholesterol/PTCH2	-0.067	0.16	-10000	0	-0.31	142	142
SHH Np/Cholesterol/Megalin	-0.17	0.22	-10000	0	-0.36	257	257
SHH	-0.079	0.19	-10000	0	-0.41	123	123
catabolic process	-0.047	0.18	-10000	0	-0.53	35	35
SMO/Vitamin D3	-0.084	0.22	-10000	0	-0.52	65	65
SHH Np/Cholesterol/Hhip	-0.14	0.21	-10000	0	-0.35	223	223
LRP2	-0.19	0.27	-10000	0	-0.55	185	185
receptor-mediated endocytosis	-0.18	0.22	-10000	0	-0.55	100	100
SHH Np/Cholesterol/BOC	-0.057	0.15	-10000	0	-0.31	126	126
SHH Np/Cholesterol/CDO	-0.075	0.17	-10000	0	-0.33	148	148
mesenchymal cell differentiation	0.15	0.2	0.35	223	-10000	0	223
mol:Vitamin D3	-0.091	0.22	-10000	0	-0.52	69	69
IHH N/PTCH2	-0.011	0.11	-10000	0	-0.45	25	25
CDON	-0.025	0.14	-10000	0	-0.56	35	35
IHH N/PTCH1	-0.047	0.19	-10000	0	-0.53	35	35
Megalin/LRPAP1	-0.14	0.19	-10000	0	-0.39	185	185
PTCH2	-0.009	0.11	-10000	0	-0.56	21	21
SHH Np/Cholesterol	-0.075	0.14	-10000	0	-0.32	123	123
PTCH1	-0.047	0.18	-10000	0	-0.53	35	35
HHIP	-0.14	0.25	-10000	0	-0.55	140	140

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.14	0.18	-10000	0	-0.45	106	106
FYN	-0.14	0.27	-10000	0	-0.54	125	125
LAT/GRAP2/SLP76	-0.16	0.22	-10000	0	-0.49	126	126
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.1	0.19	-10000	0	-0.38	120	120
B2M	0.007	0.051	-10000	0	-0.5	5	5
IKBKG	-0.034	0.046	-10000	0	-0.16	15	15
MAP3K8	-0.006	0.1	-10000	0	-0.51	20	20
mol:Ca2+	-0.025	0.042	-10000	0	-0.11	99	99
integrin-mediated signaling pathway	-0.009	0.055	-10000	0	-0.32	15	15
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.16	0.26	-10000	0	-0.53	132	132
TRPV6	-0.11	0.23	-10000	0	-0.56	106	106
CD28	-0.075	0.2	-10000	0	-0.54	81	81
SHC1	-0.14	0.26	-10000	0	-0.53	127	127
receptor internalization	-0.13	0.23	-10000	0	-0.49	115	115
PRF1	-0.17	0.36	-10000	0	-0.84	87	87
KRAS	0.013	0.022	-10000	0	-0.49	1	1
GRB2	0.013	0.022	-10000	0	-0.49	1	1
COT/AKT1	-0.082	0.16	-10000	0	-0.33	107	107
LAT	-0.16	0.26	-10000	0	-0.52	136	136
EntrezGene:6955	-0.002	0.006	-10000	0	-10000	0	0
CD3D	-0.11	0.23	-10000	0	-0.53	117	117
CD3E	-0.13	0.25	-10000	0	-0.54	136	136
CD3G	-0.035	0.14	-10000	0	-0.5	43	43
RASGRP2	-0.006	0.025	-10000	0	-0.18	3	3
RASGRP1	-0.11	0.2	-10000	0	-0.4	118	118
HLA-A	0.002	0.071	-10000	0	-0.5	10	10
RASSF5	-0.002	0.093	-10000	0	-0.54	15	15
RAP1A/GTP/RAPL	-0.009	0.055	-10000	0	-0.32	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.015	0.062	-10000	0	-0.12	45	45
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.063	0.08	-10000	0	-0.24	46	46
PRKCA	-0.079	0.1	-10000	0	-0.26	88	88
GRAP2	-0.047	0.17	-10000	0	-0.53	57	57
mol:IP3	-0.1	0.19	0.21	49	-0.38	111	160
EntrezGene:6957	-0.002	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.11	0.21	-10000	0	-0.44	116	116
ORAI1	0.068	0.12	0.31	105	-0.36	1	106
CSK	-0.15	0.26	-10000	0	-0.53	128	128
B7 family/CD28	-0.21	0.27	-10000	0	-0.57	147	147
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.17	0.29	-10000	0	-0.57	141	141
PTPN6	-0.15	0.27	-10000	0	-0.54	135	135
VAV1	-0.16	0.27	-10000	0	-0.55	133	133
Monovalent TCR/CD3	-0.11	0.19	-10000	0	-0.36	171	171
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.17	0.29	-10000	0	-0.56	148	148
PAG1	-0.15	0.26	-10000	0	-0.53	128	128
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.17	0.29	-10000	0	-0.58	132	132
CD80	-0.046	0.16	-10000	0	-0.51	56	56
CD86	-0.026	0.14	-10000	0	-0.56	35	35
PDK1/CARD11/BCL10/MALT1	-0.077	0.097	-10000	0	-0.27	68	68
HRAS	0.014	0	-10000	0	-10000	0	0
GO:0035030	-0.15	0.24	-10000	0	-0.48	144	144
CD8A	-0.078	0.21	-10000	0	-0.55	83	83
CD8B	-0.034	0.16	-10000	0	-0.56	41	41
PTPRC	-0.042	0.17	-10000	0	-0.54	51	51
PDK1/PKC theta	-0.12	0.23	-10000	0	-0.47	117	117
CSK/PAG1	-0.14	0.25	-10000	0	-0.53	119	119
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.004	0.071	-10000	0	-0.43	12	12
GRAP2/SLP76	-0.18	0.25	-10000	0	-0.54	136	136
STIM1	0.037	0.061	-10000	0	-10000	0	0
RAS family/GTP	-0.022	0.083	-10000	0	-0.17	27	27
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.13	0.24	-10000	0	-0.52	114	114
mol:DAG	-0.11	0.15	-10000	0	-0.34	114	114
RAP1A/GDP	-0.005	0.027	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.02	0.13	-10000	0	-0.52	31	31
cytotoxic T cell degranulation	-0.16	0.34	-10000	0	-0.79	88	88
RAP1A/GTP	-0.004	0.007	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.13	0.22	-10000	0	-0.44	129	129
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.14	0.23	0.23	42	-0.49	112	154
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.047	0.17	-10000	0	-0.53	57	57
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
LAT/GRAP2/SLP76/VAV1	-0.16	0.21	-10000	0	-0.48	128	128
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
CD8 heterodimer	-0.081	0.2	-10000	0	-0.46	105	105
CARD11	-0.009	0.11	-10000	0	-0.57	20	20
PRKCB	-0.1	0.11	-10000	0	-0.27	128	128
PRKCE	-0.082	0.1	-10000	0	-0.26	90	90
PRKCQ	-0.15	0.25	-10000	0	-0.52	125	125
LCP2	-0.001	0.086	-10000	0	-0.5	15	15
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.087	0.16	-10000	0	-0.33	120	120
IKK complex	-0.01	0.061	-10000	0	-0.11	24	24
RAS family/GDP	-0.007	0.009	-10000	0	-10000	0	0
MAP3K14	-0.055	0.13	-10000	0	-0.27	78	78
PDPK1	-0.096	0.18	-10000	0	-0.37	112	112
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.3	-10000	0	-0.58	147	147

×

Syndecan-1-mediated signaling events

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.08	-9999	-0.59	9	9
CCL5	-0.086	0.21	-9999	-0.53	94	94
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.13	0.19	-9999	-0.48	74	74
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.12	0.18	-9999	-0.45	75	75
Syndecan-1/Syntenin	-0.12	0.18	-9999	-0.45	74	74
MAPK3	-0.094	0.16	-9999	-0.48	42	42
HGF/MET	-0.17	0.22	-9999	-0.43	203	203
TGFB1/TGF beta receptor Type II	0.004	0.079	-9999	-0.59	9	9
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.12	0.18	-9999	-0.44	75	75
Syndecan-1/RANTES	-0.17	0.22	-9999	-0.49	117	117
Syndecan-1/CD147	-0.11	0.17	-9999	-0.43	74	74
Syndecan-1/Syntenin/PIP2	-0.12	0.17	-9999	-0.44	74	74
LAMA5	0.012	0.035	-9999	-0.54	2	2
positive regulation of cell-cell adhesion	-0.13	0.15	-9999	-0.43	74	74
MMP7	-0.15	0.25	-9999	-0.54	152	152
HGF	-0.079	0.2	-9999	-0.51	91	91
Syndecan-1/CASK	-0.13	0.18	-9999	-0.46	74	74
Syndecan-1/HGF/MET	-0.23	0.25	-9999	-0.53	164	164
regulation of cell adhesion	-0.084	0.16	-9999	-0.46	42	42
HPSE	-0.053	0.19	-9999	-0.56	60	60
positive regulation of cell migration	-0.13	0.19	-9999	-0.48	74	74
SDC1	-0.14	0.19	-9999	-0.48	74	74
Syndecan-1/Collagen	-0.13	0.19	-9999	-0.48	74	74
PPIB	0.014	0	-9999	-10000	0	0
MET	-0.15	0.25	-9999	-0.53	150	150
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
MAPK1	-0.094	0.16	-9999	-0.48	42	42
homophilic cell adhesion	-0.13	0.18	-9999	-0.47	74	74
MMP1	-0.046	0.16	-9999	-0.49	55	55

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.39	0.43	-10000	0	-1.1	81	81
STAT6 (cleaved dimer)	-0.47	0.43	-10000	0	-1	158	158
IGHG1	-0.16	0.21	-10000	0	-0.82	18	18
IGHG3	-0.38	0.41	-10000	0	-0.98	116	116
AKT1	-0.24	0.29	-10000	0	-0.75	70	70
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.3	-10000	0	-0.77	73	73
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.26	-10000	0	-0.7	56	56
THY1	-0.4	0.46	-10000	0	-1.2	84	84
MYB	-0.064	0.19	-10000	0	-0.54	72	72
HMGA1	0.01	0.047	-10000	0	-0.52	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.32	0.34	-10000	0	-0.8	121	121
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.27	-10000	0	-0.72	56	56
SP1	0.02	0.011	-10000	0	-10000	0	0
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
SOCS5	0.027	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.45	0.45	-10000	0	-1	144	144
SOCS1	-0.3	0.33	-10000	0	-0.8	87	87
SOCS3	-0.35	0.4	-10000	0	-0.98	111	111
FCER2	-0.42	0.44	-10000	0	-1.1	103	103
PARP14	-0.002	0.085	-10000	0	-0.52	13	13
CCL17	-0.4	0.44	-10000	0	-1.1	90	90
GRB2	0.013	0.022	-10000	0	-0.49	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.23	-10000	0	-0.65	49	49
T cell proliferation	-0.41	0.45	-10000	0	-1.1	104	104
IL4R/JAK1	-0.4	0.43	-10000	0	-1.1	87	87
EGR2	-0.51	0.54	-10000	0	-1.3	129	129
JAK2	-0.004	0.027	-10000	0	-10000	0	0
JAK3	-0.057	0.18	-10000	0	-0.53	67	67
PIK3R1	0.014	0	-10000	0	-10000	0	0
JAK1	0.005	0.012	-10000	0	-10000	0	0
COL1A2	-0.16	0.25	-10000	0	-0.72	51	51
CCL26	-0.4	0.44	-10000	0	-1.1	91	91
IL4R	-0.42	0.46	-10000	0	-1.2	86	86
PTPN6	0.006	0.099	-10000	0	-0.54	16	16
IL13RA2	-0.61	0.58	-10000	0	-1.3	193	193
IL13RA1	-0.015	0.084	-10000	0	-0.61	9	9
IRF4	-0.17	0.33	-10000	0	-1.1	43	43
ARG1	-0.13	0.23	-10000	0	-0.86	27	27
CBL	-0.3	0.32	-10000	0	-0.77	109	109
GTF3A	0.009	0.034	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL13RA1/JAK2	-0.015	0.07	-10000	0	-0.45	9	9
IRF4/BCL6	-0.15	0.31	-10000	0	-1	42	42
CD40LG	-0.035	0.15	-10000	0	-0.5	46	46
MAPK14	-0.32	0.35	-10000	0	-0.82	117	117
mitosis	-0.23	0.27	-10000	0	-0.72	67	67
STAT6	-0.45	0.5	-10000	0	-1.2	110	110
SPI1	-0.004	0.11	-10000	0	-0.54	19	19
RPS6KB1	-0.21	0.26	-10000	0	-0.69	63	63
STAT6 (dimer)	-0.45	0.5	-10000	0	-1.2	110	110
STAT6 (dimer)/PARP14	-0.43	0.46	-10000	0	-1.1	116	116
mast cell activation	0.011	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.27	0.31	-10000	0	-0.8	88	88
FRAP1	-0.24	0.29	-10000	0	-0.75	70	70
LTA	-0.42	0.48	-10000	0	-1.2	94	94
FES	0.01	0.047	-10000	0	-0.52	4	4
T-helper 1 cell differentiation	0.44	0.48	1.1	111	-10000	0	111
CCL11	-0.38	0.41	-10000	0	-1	92	92
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.25	0.3	-10000	0	-0.79	76	76
IL2RG	-0.042	0.16	-10000	0	-0.52	54	54
IL10	-0.49	0.56	-10000	0	-1.3	125	125
IRS1	0.014	0	-10000	0	-10000	0	0
IRS2	0.012	0.035	-10000	0	-0.54	2	2
IL4	-0.097	0.11	-10000	0	-10000	0	0
IL5	-0.4	0.43	-10000	0	-1.1	83	83
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.32	0.35	-10000	0	-0.85	85	85
COL1A1	-0.35	0.5	-10000	0	-1.1	126	126
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.39	0.44	-10000	0	-1.2	73	73
IL2R gamma/JAK3	-0.073	0.19	-10000	0	-0.44	101	101
TFF3	-0.41	0.45	-10000	0	-1.2	85	85
ALOX15	-0.4	0.44	-10000	0	-1.1	90	90
MYBL1	0.01	0.044	-10000	0	-0.49	4	4
T-helper 2 cell differentiation	-0.36	0.37	-10000	0	-0.88	112	112
SHC1	0.009	0.05	-10000	0	-0.49	5	5
CEBPB	-0.003	0.11	-10000	0	-0.56	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.26	-10000	0	-0.68	59	59
mol:PI-3-4-5-P3	-0.24	0.29	-10000	0	-0.76	70	70
PI3K	-0.25	0.31	-10000	0	-0.81	70	70
DOK2	-0.071	0.2	-10000	0	-0.53	80	80
ETS1	0.015	0.076	-10000	0	-0.51	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.17	0.22	-10000	0	-0.62	47	47
ITGB3	-0.43	0.48	-10000	0	-1.2	103	103
PIGR	-0.49	0.55	-10000	0	-1.3	115	115
IGHE	0.021	0.061	-10000	0	-0.25	12	12
MAPKKK cascade	-0.17	0.22	-10000	0	-0.61	47	47
BCL6	0.016	0.006	-10000	0	-10000	0	0
OPRM1	-0.41	0.44	-10000	0	-1.1	91	91
RETNLB	-0.4	0.43	-10000	0	-1.1	87	87
SELP	-0.4	0.44	-10000	0	-1.1	82	82
AICDA	-0.38	0.42	-10000	0	-1.1	85	85

×

Syndecan-4-mediated signaling events

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
PTK2	0	0.055	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.24	-9999	-0.56	99	99
positive regulation of JNK cascade	-0.14	0.22	-9999	-0.52	107	107
Syndecan-4/ADAM12	-0.17	0.26	-9999	-0.57	118	118
CCL5	-0.086	0.21	-9999	-0.53	94	94
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.01	0.11	-9999	-0.5	24	24
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0.002	0.038	-9999	-0.48	3	3
ADAM12	-0.072	0.19	-9999	-0.5	85	85
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.042	-9999	-0.18	1	1
Syndecan-4/Laminin alpha1	-0.17	0.27	-9999	-0.59	115	115
Syndecan-4/CXCL12/CXCR4	-0.13	0.25	-9999	-0.55	107	107
Syndecan-4/Laminin alpha3	-0.16	0.26	-9999	-0.58	111	111
MDK	-0.042	0.17	-9999	-0.54	52	52
Syndecan-4/FZD7	-0.16	0.28	-9999	-0.61	111	111
Syndecan-4/Midkine	-0.16	0.26	-9999	-0.58	106	106
FZD7	-0.047	0.18	-9999	-0.58	53	53
Syndecan-4/FGFR1/FGF	-0.14	0.2	-9999	-0.51	101	101
THBS1	-0.088	0.21	-9999	-0.51	100	100
integrin-mediated signaling pathway	-0.15	0.26	-9999	-0.57	109	109
positive regulation of MAPKKK cascade	-0.14	0.22	-9999	-0.52	107	107
Syndecan-4/TACI	-0.14	0.24	-9999	-0.56	100	100
CXCR4	-0.013	0.12	-9999	-0.54	25	25
cell adhesion	0.021	0.052	-9999	-0.26	11	11
Syndecan-4/Dynamin	-0.13	0.24	-9999	-0.56	99	99
Syndecan-4/TSP1	-0.18	0.26	-9999	-0.58	119	119
Syndecan-4/GIPC	-0.13	0.24	-9999	-0.56	99	99
Syndecan-4/RANTES	-0.18	0.26	-9999	-0.59	112	112
ITGB1	0.012	0.031	-9999	-0.49	2	2
LAMA1	-0.065	0.2	-9999	-0.57	70	70
LAMA3	-0.041	0.17	-9999	-0.54	51	51
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.037	0.052	-9999	-0.53	1	1
Syndecan-4/alpha-Actinin	-0.14	0.25	-9999	-0.57	110	110
TFPI	-0.091	0.21	-9999	-0.52	100	100
F2	-0.007	0.066	-9999	-0.49	9	9
alpha5/beta1 Integrin	-0.018	0.079	-9999	-0.36	25	25
positive regulation of cell adhesion	-0.18	0.28	-9999	-0.59	131	131
ACTN1	-0.021	0.13	-9999	-0.5	35	35
TNC	-0.049	0.18	-9999	-0.54	59	59
Syndecan-4/CXCL12	-0.13	0.24	-9999	-0.56	102	102
FGF6	0.001	0.003	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	0.003	0.077	-9999	-0.54	10	10
TNFRSF13B	-0.005	0.072	-9999	-0.49	11	11
FGF2	0.011	0.044	-9999	-0.56	3	3
FGFR1	0.013	0.027	-9999	-0.59	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.24	-9999	-0.56	99	99
mol:GDP	0	0	-9999	-10000	0	0
FN1	0	0.093	-9999	-0.48	18	18
cell migration	-0.007	0.018	-9999	-10000	0	0
PRKCD	-0.014	0.13	-9999	-0.57	27	27
vasculogenesis	-0.17	0.25	-9999	-0.55	119	119
SDC4	-0.14	0.25	-9999	-0.6	99	99
Syndecan-4/Tenascin C	-0.16	0.27	-9999	-0.6	109	109
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.033	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.24	-9999	-0.56	99	99
MMP9	-0.14	0.24	-9999	-0.52	144	144
Rac1/GTP	0.021	0.053	-9999	-0.26	11	11
cytoskeleton organization	-0.12	0.23	-9999	-0.53	99	99
GIPC1	0.013	0.022	-9999	-0.49	1	1
Syndecan-4/TFPI	-0.18	0.26	-9999	-0.6	107	107

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.042	0.17	-9999	-0.54	52	52
GPC2	-0.016	0.13	-9999	-0.57	26	26
GPC2/Midkine	-0.059	0.15	-9999	-0.42	73	73
neuron projection morphogenesis	-0.059	0.15	-9999	-0.41	73	73

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.038	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.091	0.14	-9999	-0.42	48	48
JUN	-0.079	0.2	-9999	-0.52	58	58
HRAS	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.16	0.22	-9999	-0.44	144	144
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.012	0.035	-9999	-0.54	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.16	0.22	-9999	-0.44	143	143
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.094	0.17	-9999	-0.35	136	136
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.14	0.2	-9999	-0.61	54	54
GRB7	-0.031	0.14	-9999	-0.49	42	42
RET51/GFRalpha1/GDNF	-0.15	0.21	-9999	-0.43	143	143
MAPKKK cascade	-0.12	0.18	-9999	-0.56	50	50
BCAR1	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.089	0.16	-9999	-0.35	130	130
lamellipodium assembly	-0.085	0.13	-9999	-0.37	57	57
RET51/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.44	143	143
PIK3CA	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/SHC	-0.092	0.17	-9999	-0.36	131	131
RET9/GFRalpha1/GDNF/Shank3	-0.094	0.17	-9999	-0.35	137	137
MAPK3	-0.11	0.21	-9999	-0.57	54	54
DOK1	0.012	0.035	-9999	-0.54	2	2
DOK6	-0.048	0.18	-9999	-0.58	54	54
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.099	0.22	-9999	-0.54	68	68
DOK5	0.001	0.088	-9999	-0.59	11	11
GFRA1	-0.071	0.2	-9999	-0.56	76	76
MAPK8	-0.086	0.2	-9999	-0.56	51	51
HRAS/GTP	-0.14	0.2	-9999	-0.55	65	65
tube development	-0.088	0.16	-9999	-0.37	96	96
MAPK1	-0.11	0.21	-9999	-0.57	54	54
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.14	-9999	-0.31	94	94
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.005	0.066	-9999	-0.49	9	9
RET51/GFRalpha1/GDNF/Dok6	-0.17	0.25	-9999	-0.48	151	151
SHC1	0.009	0.05	-9999	-0.49	5	5
RET51/GFRalpha1/GDNF/Dok4	-0.16	0.22	-9999	-0.45	150	150
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.44	151	151
PRKCA	0.013	0.027	-9999	-0.59	1	1
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.068	0.18	-9999	-0.48	56	56
PIK3R1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.044	0.15	-9999	-0.32	94	94
RET51/GFRalpha1/GDNF/Grb7	-0.18	0.23	-9999	-0.47	146	146
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.24	-9999	-0.55	118	118
DOK4	-0.005	0.1	-9999	-0.59	16	16
JNK cascade	-0.077	0.19	-9999	-0.5	58	58
RET9/GFRalpha1/GDNF/FRS2	-0.09	0.17	-9999	-0.35	131	131
SHANK3	0.004	0.073	-9999	-0.51	10	10
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.042	0.15	-9999	-0.32	94	94
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.092	0.2	-9999	-0.58	46	46
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.092	0.2	-9999	-0.57	48	48
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.096	0.21	-9999	-0.61	47	47
PI3K	-0.089	0.23	-9999	-0.56	65	65
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.088	0.16	-9999	-0.37	96	96
GRB10	0.011	0.044	-9999	-0.56	3	3
activation of MAPKK activity	-0.086	0.2	-9999	-0.46	82	82
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.43	143	143
GAB1	0.012	0.035	-9999	-0.54	2	2
IRS1	0.014	0	-9999	-10000	0	0
IRS2	0.012	0.035	-9999	-0.54	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.097	0.21	-9999	-0.52	64	64
RET51/GFRalpha1/GDNF/PKC alpha	-0.15	0.22	-9999	-0.43	143	143
GRB2	0.013	0.022	-9999	-0.49	1	1
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.071	0.2	-9999	-0.57	73	73
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.15	0.21	-9999	-0.43	143	143
Rac1/GTP	-0.1	0.15	-9999	-0.45	57	57
RET9/GFRalpha1/GDNF	-0.1	0.18	-9999	-0.39	130	130
GFRalpha1/GDNF	-0.12	0.21	-9999	-0.46	130	130

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.008	0.05	-10000	0	-0.49	5	5
GNB1/GNG2	-0.078	0.08	-10000	0	-0.19	107	107
AKT1	-0.059	0.12	-10000	0	-0.22	57	57
EGF	-0.05	0.18	-10000	0	-0.56	58	58
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.017	0.07	-10000	0	-0.35	2	2
mol:Ca2+	-0.099	0.16	-10000	0	-0.3	151	151
LYN	0.014	0.079	-10000	0	-0.34	8	8
RhoA/GTP	-0.051	0.052	-10000	0	-0.14	27	27
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.12	0.18	-10000	0	-0.36	151	151
GNG2	0.009	0.053	-10000	0	-0.59	4	4
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.01	0.098	-10000	0	-0.39	24	24
G beta5/gamma2	-0.097	0.1	-10000	0	-0.25	106	106
PRKCH	-0.11	0.17	-10000	0	-0.34	138	138
DNM1	-0.1	0.22	-10000	0	-0.52	109	109
TXA2/TP beta/beta Arrestin3	-0.041	0.071	-10000	0	-0.24	29	29
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.039	0.16	-10000	0	-0.5	52	52
G12 family/GTP	-0.13	0.13	-10000	0	-0.3	149	149
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.051	-10000	0	-0.57	4	4
RhoA/GTP/ROCK1	0.004	0.008	-10000	0	-10000	0	0
mol:GDP	0.057	0.11	0.3	30	-10000	0	30
mol:NADP	0.005	0.071	-10000	0	-0.52	9	9
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.039	0.17	-10000	0	-0.58	46	46
mol:IP3	-0.13	0.19	-10000	0	-0.37	151	151
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.17	0.25	-10000	0	-0.51	148	148
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.039	0.11	-10000	0	-0.35	13	13
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.009	0.088	-10000	0	-0.36	9	9
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.015	0.12	-10000	0	-0.52	28	28
PRKCB1	-0.12	0.19	-10000	0	-0.36	151	151
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.005	0.071	-10000	0	-0.52	9	9
TXA2/TXA2-R family	-0.18	0.26	-10000	0	-0.53	151	151
LCK	-0.024	0.12	-10000	0	-0.35	17	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.025	0.066	-10000	0	-0.37	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.045	-10000	0	-0.75	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.024	0.063	-10000	0	-0.38	4	4
MAPK14	-0.07	0.13	-10000	0	-0.24	98	98
TGM2/GTP	-0.14	0.21	-10000	0	-0.42	149	149
MAPK11	-0.073	0.13	-10000	0	-0.25	104	104
ARHGEF1	-0.052	0.097	-10000	0	-0.18	74	74
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.13	0.2	-10000	0	-0.39	151	151
RAB11/GDP	0.015	0.001	-10000	0	-10000	0	0
ICAM1	-0.098	0.16	-10000	0	-0.3	156	156
cAMP biosynthetic process	-0.12	0.18	-10000	0	-0.35	152	152
Gq family/GTP/EBP50	0.007	0.083	-10000	0	-0.29	27	27
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.019	0.068	-10000	0	-0.35	2	2
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.024	0.11	-10000	0	-0.35	16	16
VCAM1	-0.12	0.19	-10000	0	-0.37	156	156
TP beta/Gq family/GDP/G beta5/gamma2	0.01	0.098	-10000	0	-0.39	24	24
platelet activation	-0.093	0.17	-10000	0	-0.3	149	149
PGI2/IP	-0.016	0.087	-10000	0	-0.38	28	28
PRKACA	-0.01	0.08	-10000	0	-0.29	18	18
Gq family/GDP/G beta5/gamma2	0.009	0.093	-10000	0	-0.36	25	25
TXA2/TP beta/beta Arrestin2	-0.061	0.14	-10000	0	-0.53	34	34
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.005	0.086	-10000	0	-0.36	9	9
mol:DAG	-0.14	0.21	-10000	0	-0.41	152	152
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
TXA2/TP alpha	-0.17	0.24	-10000	0	-0.48	150	150
Gq family/GTP	-0.016	0.068	-10000	0	-0.24	38	38
YES1	0.017	0.072	-10000	0	-0.35	2	2
GNAI2/GTP	-0.024	0.061	-10000	0	-0.35	5	5
PGD2/DP	-0.033	0.11	-10000	0	-0.36	52	52
SLC9A3R1	0.009	0.053	-10000	0	-0.59	4	4
FYN	0.019	0.068	-10000	0	-0.35	2	2
mol:NO	0.005	0.071	-10000	0	-0.52	9	9
GNA15	-0.007	0.11	-10000	0	-0.56	19	19
PGK/cGMP	-0.037	0.11	-10000	0	-0.35	54	54
RhoA/GDP	0.015	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.023	0.074	-10000	0	-0.42	6	6
NOS3	0.005	0.071	-10000	0	-0.52	9	9
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.11	0.18	-10000	0	-0.34	138	138
PRKCB	-0.13	0.2	-10000	0	-0.38	164	164
PRKCE	-0.11	0.18	-10000	0	-0.35	139	139
PRKCD	-0.13	0.2	-10000	0	-0.39	151	151
PRKCG	-0.17	0.22	-10000	0	-0.43	176	176
muscle contraction	-0.17	0.24	-10000	0	-0.49	155	155
PRKCZ	-0.12	0.18	-10000	0	-0.35	160	160
ARR3	0.002	0.023	-10000	0	-0.49	1	1
TXA2/TP beta	-0.025	0.07	-10000	0	-0.39	5	5
PRKCQ	-0.12	0.18	-10000	0	-0.35	155	155
MAPKKK cascade	-0.16	0.22	-10000	0	-0.45	153	153
SELE	-0.12	0.18	-10000	0	-0.33	173	173
TP beta/GNAI2/GDP/G beta/gamma	-0.021	0.067	-10000	0	-0.37	5	5
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
chemotaxis	-0.21	0.3	-10000	0	-0.61	149	149
GNA12	0.013	0.027	-10000	0	-0.59	1	1
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.004	0.08	-10000	0	-0.59	9	9
Rac1/GTP	0.004	0.005	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.025	0.1	-9999	-0.42	30	30
VLDLR	-0.007	0.11	-9999	-0.56	19	19
CRKL	0.013	0.022	-9999	-0.49	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ITGA3	-0.009	0.11	-9999	-0.5	23	23
RELN/VLDLR/Fyn	-0.1	0.16	-9999	-0.34	152	152
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.053	-9999	-10000	0	0
AKT1	-0.072	0.16	-9999	-0.49	30	30
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.089	0.22	-9999	-0.56	92	92
RELN/LRP8/DAB1	-0.14	0.18	-9999	-0.35	201	201
LRPAP1/LRP8	-0.002	0.027	-9999	-0.43	2	2
RELN/LRP8/DAB1/Fyn	-0.12	0.17	-9999	-0.36	139	139
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.53	52	52
long-term memory	-0.28	0.28	-9999	-0.64	161	161
DAB1/LIS1	-0.12	0.17	-9999	-0.54	40	40
DAB1/CRLK/C3G	-0.12	0.16	-9999	-0.52	40	40
PIK3CA	0.013	0.027	-9999	-0.59	1	1
DAB1/NCK2	-0.12	0.17	-9999	-0.54	40	40
ARHGEF2	0.013	0.027	-9999	-0.59	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.15	0.26	-9999	-0.55	154	154
CDK5R1	-0.021	0.14	-9999	-0.59	30	30
RELN	-0.14	0.25	-9999	-0.55	139	139
PIK3R1	0.014	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.089	0.15	-9999	-0.32	140	140
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.2	0.23	-9999	-0.59	103	103
MAPK8	-0.001	0.095	-9999	-0.59	13	13
RELN/VLDLR/DAB1	-0.14	0.19	-9999	-0.36	210	210
ITGB1	0.012	0.031	-9999	-0.49	2	2
MAP1B	-0.11	0.2	-9999	-0.37	141	141
RELN/LRP8	-0.089	0.15	-9999	-0.32	140	140
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.21	0.23	-9999	-0.59	104	104
PI3K	-0.001	0.019	-9999	-0.43	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.017	0.078	-9999	-0.36	24	24
RAP1A	-0.072	0.18	-9999	-0.49	40	40
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.053	-9999	-0.59	4	4
CRLK/C3G	-0.001	0.015	-9999	-0.34	1	1
GRIN2B	-0.18	0.26	-9999	-0.54	177	177
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.042	0.14	-9999	-0.42	33	33
neuron adhesion	-0.065	0.18	-9999	-0.49	44	44
LRP8	0.012	0.038	-9999	-0.59	2	2
GSK3B	-0.061	0.15	-9999	-0.47	30	30
RELN/VLDLR/DAB1/Fyn	-0.13	0.18	-9999	-0.37	148	148
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.085	0.17	-9999	-0.31	148	148
CDK5	0.014	0	-9999	-10000	0	0
MAPT	0.011	0.082	-9999	-0.54	10	10
neuron migration	-0.07	0.19	-9999	-0.51	42	42
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.14	-9999	-0.42	33	33
RELN/VLDLR	-0.09	0.14	-9999	-0.34	93	93

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0.027	-9999	-0.59	1	1
Aurora C/Aurora B/INCENP	-0.11	0.16	-9999	-0.31	179	179
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.032	0.045	-9999	-0.25	1	1
AURKB	-0.16	0.26	-9999	-0.55	156	156
AURKC	-0.022	0.14	-9999	-0.52	35	35

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.079	0.17	-9999	-0.45	79	79
alphaM/beta2 Integrin/GPIbA	-0.074	0.17	-9999	-0.45	73	73
alphaM/beta2 Integrin/proMMP-9	-0.15	0.21	-9999	-0.4	182	182
PLAUR	-0.02	0.13	-9999	-0.5	34	34
HMGB1	-0.001	0.022	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.063	0.16	-9999	-0.48	57	57
AGER	-0.029	0.13	-9999	-0.6	24	24
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	-0.023	0.14	-9999	-0.58	32	32
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.13	0.18	-9999	-0.47	85	85
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
CYR61	-0.1	0.23	-9999	-0.55	104	104
TLN1	0.014	0	-9999	-10000	0	0
Rap1/GTP	-0.089	0.13	-9999	-0.41	45	45
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.026	0.13	-9999	-0.49	37	37
MYH2	-0.086	0.15	-9999	-0.4	59	59
MST1R	0.006	0.069	-9999	-0.58	7	7
leukocyte activation during inflammatory response	-0.11	0.18	-9999	-0.39	117	117
APOB	-0.072	0.2	-9999	-0.55	78	78
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.013	0.12	-9999	-0.54	25	25
JAM3	0.014	0	-9999	-10000	0	0
GP1BA	-0.004	0.1	-9999	-0.57	16	16
alphaM/beta2 Integrin/CTGF	-0.088	0.18	-9999	-0.44	91	91
alphaM/beta2 Integrin	-0.097	0.16	-9999	-0.42	70	70
JAM3 homodimer	0.014	0	-9999	-10000	0	0
ICAM2	0.013	0.022	-9999	-0.49	1	1
ICAM1	-0.028	0.14	-9999	-0.51	41	41
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.096	0.16	-9999	-0.41	70	70
cell adhesion	-0.074	0.16	-9999	-0.45	73	73
NFKB1	-0.16	0.26	-9999	-0.61	84	84
THY1	-0.004	0.1	-9999	-0.56	16	16
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.068	0.14	-9999	-0.33	107	107
alphaM/beta2 Integrin/LRP/tPA	-0.084	0.17	-9999	-0.46	66	66
IL6	-0.2	0.33	-9999	-0.75	100	100
ITGB2	-0.045	0.15	-9999	-0.57	39	39
elevation of cytosolic calcium ion concentration	-0.11	0.2	-9999	-0.45	107	107
alphaM/beta2 Integrin/JAM2/JAM3	-0.052	0.15	-9999	-0.44	55	55
JAM2	0.013	0.027	-9999	-0.59	1	1
alphaM/beta2 Integrin/ICAM1	-0.089	0.18	-9999	-0.49	55	55
alphaM/beta2 Integrin/uPA/Plg	-0.097	0.18	-9999	-0.43	95	95
RhoA/GTP	-0.089	0.16	-9999	-0.41	59	59
positive regulation of phagocytosis	-0.1	0.18	-9999	-0.58	46	46
Ron/MSP	-0.034	0.11	-9999	-0.41	42	42
alphaM/beta2 Integrin/uPAR/uPA	-0.11	0.2	-9999	-0.45	107	107
alphaM/beta2 Integrin/uPAR	-0.083	0.18	-9999	-0.46	83	83
PLAU	-0.059	0.18	-9999	-0.51	72	72
PLAT	-0.05	0.17	-9999	-0.49	65	65
actin filament polymerization	-0.083	0.15	-9999	-0.38	60	60
MST1	-0.026	0.15	-9999	-0.57	35	35
alphaM/beta2 Integrin/lipoprotein(a)	-0.11	0.18	-9999	-0.4	117	117
TNF	-0.23	0.35	-9999	-0.76	126	126
RAP1B	0.013	0.022	-9999	-0.49	1	1
alphaM/beta2 Integrin/uPA	-0.1	0.19	-9999	-0.43	115	115
fibrinolysis	-0.096	0.18	-9999	-0.43	95	95
HCK	-0.007	0.11	-9999	-0.54	20	20
dendritic cell antigen processing and presentation	-0.096	0.16	-9999	-0.41	70	70
VTN	-0.007	0.11	-9999	-0.56	19	19
alphaM/beta2 Integrin/CYR61	-0.13	0.22	-9999	-0.45	139	139
LPA	-0.02	0.12	-9999	-0.49	31	31
LRP1	0.014	0	-9999	-10000	0	0
cell migration	-0.13	0.22	-9999	-0.45	124	124
FN1	-0.004	0.093	-9999	-0.49	18	18
alphaM/beta2 Integrin/Thy1	-0.074	0.17	-9999	-0.46	72	72
MPO	-0.12	0.24	-9999	-0.54	127	127
KNG1	-0.019	0.1	-9999	-0.49	24	24
RAP1/GDP	-0.001	0.013	-9999	-0.29	1	1
ROCK1	-0.076	0.15	-9999	-0.39	53	53
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.038	-9999	-0.49	3	3
CTGF	-0.029	0.15	-9999	-0.54	40	40
alphaM/beta2 Integrin/Hck	-0.075	0.2	-9999	-0.57	57	57
ITGAM	-0.045	0.16	-9999	-0.6	37	37
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.091	0.21	-9999	-0.56	65	65
HP	-0.11	0.23	-9999	-0.53	115	115
leukocyte adhesion	-0.11	0.17	-9999	-0.54	52	52
SELP	-0.026	0.13	-9999	-0.49	37	37

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0.031	-9999	-0.49	2	2
ITGB7	-0.033	0.16	-9999	-0.54	44	44
ITGA4	-0.051	0.18	-9999	-0.53	61	61
alpha4/beta7 Integrin	-0.076	0.17	-9999	-0.43	92	92
alpha4/beta1 Integrin	-0.046	0.13	-9999	-0.39	61	61

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.15	0.38	-9999	-1	67	67
MKNK1	0.009	0.053	-9999	-0.59	4	4
MAPK14	-0.038	0.12	-9999	-0.36	8	8
ATF2/c-Jun	-0.028	0.14	-9999	-0.57	17	17
MAPK11	-0.049	0.15	-9999	-0.55	16	16
MITF	-0.042	0.16	-9999	-0.35	85	85
MAPKAPK5	-0.039	0.16	-9999	-0.34	85	85
KRT8	-0.11	0.22	-9999	-0.42	131	131
MAPKAPK3	0.012	0.038	-9999	-0.59	2	2
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.062	0.19	-9999	-0.43	88	88
CEBPB	-0.053	0.18	-9999	-0.4	88	88
SLC9A1	-0.041	0.16	-9999	-0.35	88	88
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.045	0.17	-9999	-0.56	16	16
p38alpha-beta/MNK1	-0.039	0.16	-9999	-0.55	14	14
JUN	-0.028	0.14	-9999	-0.57	17	17
PPARGC1A	-0.056	0.18	-9999	-0.39	97	97
USF1	-0.039	0.16	-9999	-0.34	85	85
RAB5/GDP/GDI1	-0.052	0.095	-9999	-0.43	7	7
NOS2	-0.083	0.28	-9999	-1	27	27
DDIT3	-0.044	0.16	-9999	-0.35	86	86
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.042	0.15	-9999	-0.46	22	22
p38alpha-beta/HBP1	-0.036	0.16	-9999	-0.53	10	10
CREB1	-0.041	0.17	-9999	-0.37	85	85
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.028	0.14	-9999	-0.56	10	10
RPS6KA4	-0.039	0.16	-9999	-0.34	85	85
PLA2G4A	-0.046	0.17	-9999	-0.61	22	22
GDI1	-0.039	0.16	-9999	-0.34	88	88
TP53	-0.061	0.2	-9999	-0.43	95	95
RPS6KA5	-0.047	0.17	-9999	-0.36	88	88
ESR1	-0.055	0.18	-9999	-0.37	97	97
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.05	0.17	-9999	-0.36	97	97
MEF2A	-0.04	0.16	-9999	-0.35	85	85
EIF4EBP1	-0.044	0.17	-9999	-0.37	86	86
KRT19	-0.1	0.22	-9999	-0.44	102	102
ELK4	-0.039	0.16	-9999	-0.34	85	85
ATF6	-0.039	0.16	-9999	-0.34	85	85
ATF1	-0.041	0.17	-9999	-0.37	85	85
p38alpha-beta/MAPKAPK2	-0.036	0.16	-9999	-0.53	10	10
p38alpha-beta/MAPKAPK3	-0.037	0.16	-9999	-0.53	12	12

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.18	0.39	-10000	0	-0.92	74	74
PCK1	-0.24	0.43	-10000	0	-1	84	84
HNF4A	-0.21	0.42	-10000	0	-1	71	71
KCNJ11	-0.25	0.51	-10000	0	-1.2	94	94
AKT1	-0.076	0.17	-10000	0	-0.41	33	33
response to starvation	-0.002	0.022	-10000	0	-10000	0	0
DLK1	-0.25	0.45	-10000	0	-1	100	100
NKX2-1	-0.076	0.22	-10000	0	-0.77	16	16
ACADM	-0.18	0.39	-10000	0	-0.92	74	74
TAT	-0.23	0.42	-10000	0	-1.1	74	74
CEBPB	-0.005	0.1	-10000	0	-0.56	17	17
CEBPA	-0.016	0.13	-10000	0	-0.56	27	27
TTR	-0.15	0.28	-10000	0	-0.77	51	51
PKLR	-0.19	0.4	-10000	0	-0.91	84	84
APOA1	-0.23	0.48	-10000	0	-1.2	73	73
CPT1C	-0.18	0.39	-10000	0	-0.92	76	76
ALAS1	-0.062	0.2	-10000	0	-0.83	2	2
TFRC	-0.17	0.31	-10000	0	-0.76	59	59
FOXF1	-0.006	0.094	-10000	0	-0.51	16	16
NF1	0.02	0.038	-10000	0	-0.59	2	2
HNF1A (dimer)	0.011	0.04	-10000	0	-0.65	1	1
CPT1A	-0.18	0.39	-10000	0	-0.92	78	78
HMGCS1	-0.18	0.39	-10000	0	-0.97	67	67
NR3C1	-0.024	0.077	-10000	0	-0.3	1	1
CPT1B	-0.2	0.41	-10000	0	-0.98	79	79
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.024	-10000	0	-10000	0	0
GCK	-0.25	0.48	-10000	0	-1	115	115
CREB1	-0.003	0.054	-10000	0	-10000	0	0
IGFBP1	-0.26	0.5	-10000	0	-1.3	86	86
PDX1	-0.08	0.21	-10000	0	-0.7	10	10
UCP2	-0.2	0.42	-10000	0	-1	79	79
ALDOB	-0.2	0.44	-10000	0	-1	77	77
AFP	-0.09	0.17	-10000	0	-0.55	33	33
BDH1	-0.21	0.45	-10000	0	-1.1	84	84
HADH	-0.18	0.41	-10000	0	-0.97	73	73
F2	-0.21	0.43	-10000	0	-1.1	59	59
HNF1A	0.011	0.04	-10000	0	-0.65	1	1
G6PC	-0.07	0.21	-10000	0	-1	13	13
SLC2A2	-0.094	0.23	-10000	0	-0.6	23	23
INS	0.013	0.091	0.24	14	-0.56	5	19
FOXA1	-0.054	0.17	-10000	0	-0.48	58	58
FOXA3	-0.12	0.23	-10000	0	-0.55	99	99
FOXA2	-0.22	0.47	-10000	0	-1.1	84	84
ABCC8	-0.27	0.53	-10000	0	-1.2	96	96
ALB	-0.13	0.3	-10000	0	-1.1	38	38

×

Endothelins

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
AKT1	-0.094	0.21	-10000	0	-0.56	51	51
PTK2B	-0.009	0.11	-10000	0	-0.49	24	24
mol:Ca2+	-0.062	0.24	-10000	0	-0.74	38	38
EDN1	-0.082	0.18	-10000	0	-0.46	72	72
EDN3	-0.017	0.13	-10000	0	-0.58	27	27
EDN2	-0.017	0.1	-10000	0	-0.49	23	23
HRAS/GDP	-0.093	0.21	-10000	0	-0.54	54	54
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.051	0.16	-10000	0	-0.47	35	35
ADCY4	-0.11	0.23	-10000	0	-0.52	89	89
ADCY5	-0.12	0.24	-10000	0	-0.56	88	88
ADCY6	-0.1	0.22	-10000	0	-0.51	85	85
ADCY7	-0.1	0.22	-10000	0	-0.51	85	85
ADCY1	-0.16	0.25	-10000	0	-0.54	117	117
ADCY2	-0.11	0.23	-10000	0	-0.53	90	90
ADCY3	-0.1	0.22	-10000	0	-0.51	85	85
ADCY8	-0.14	0.25	-10000	0	-0.53	113	113
ADCY9	-0.11	0.22	-10000	0	-0.51	87	87
arachidonic acid secretion	-0.095	0.22	-10000	0	-0.52	72	72
ETB receptor/Endothelin-1/Gq/GTP	-0.046	0.16	-10000	0	-0.4	57	57
GNAO1	0.008	0.06	-10000	0	-0.59	5	5
HRAS	0.013	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.095	0.2	0.26	18	-0.53	49	67
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.23	0.25	17	-0.54	85	102
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.19	0.32	-10000	0	-0.62	156	156
EDNRB	-0.047	0.18	-10000	0	-0.59	50	50
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.11	0.26	-10000	0	-0.68	60	60
CYSLTR1	-0.11	0.24	-10000	0	-0.64	56	56
SLC9A1	-0.067	0.099	-10000	0	-0.31	32	32
mol:GDP	-0.11	0.22	-10000	0	-0.56	64	64
SLC9A3	-0.096	0.27	-10000	0	-0.66	73	73
RAF1	-0.11	0.23	-10000	0	-0.54	70	70
JUN	-0.044	0.2	-10000	0	-0.65	23	23
JAK2	-0.094	0.21	-10000	0	-0.56	50	50
mol:IP3	-0.059	0.18	-10000	0	-0.52	38	38
ETA receptor/Endothelin-1	-0.13	0.24	0.3	20	-0.56	73	93
PLCB1	-0.01	0.11	-10000	0	-0.59	19	19
PLCB2	-0.009	0.11	-10000	0	-0.57	19	19
ETA receptor/Endothelin-3	-0.072	0.15	-10000	0	-0.47	55	55
FOS	-0.14	0.33	-10000	0	-0.86	75	75
Gai/GDP	0.006	0.11	-10000	0	-0.96	5	5
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.12	0.25	-10000	0	-0.57	82	82
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
PRKCB1	-0.058	0.17	-10000	0	-0.5	39	39
GNAQ	0.013	0.007	-10000	0	-10000	0	0
GNAZ	0.014	0	-10000	0	-10000	0	0
GNAL	-0.055	0.19	-10000	0	-0.59	59	59
Gs family/GDP	-0.15	0.21	-10000	0	-0.54	88	88
ETA receptor/Endothelin-1/Gq/GTP	-0.05	0.15	-10000	0	-0.41	43	43
MAPK14	-0.038	0.16	-10000	0	-0.54	27	27
TRPC6	-0.066	0.25	-10000	0	-0.82	35	35
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.048	0.17	-10000	0	-0.47	42	42
ETB receptor/Endothelin-2	-0.048	0.15	-10000	0	-0.41	72	72
ETB receptor/Endothelin-3	-0.048	0.17	-10000	0	-0.46	70	70
ETB receptor/Endothelin-1	-0.099	0.19	-10000	0	-0.45	95	95
MAPK3	-0.14	0.3	-10000	0	-0.75	79	79
MAPK1	-0.14	0.3	-10000	0	-0.75	79	79
Rac1/GDP	-0.092	0.21	-10000	0	-0.54	54	54
cAMP biosynthetic process	-0.12	0.24	-10000	0	-0.53	95	95
MAPK8	-0.06	0.22	-10000	0	-0.65	38	38
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.021	0.12	-10000	0	-0.36	31	31
p130Cas/CRK/Src/PYK2	-0.098	0.23	-10000	0	-0.58	56	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.093	0.21	-10000	0	-0.55	52	52
COL1A2	-0.14	0.28	-10000	0	-0.66	89	89
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.069	0.14	-10000	0	-0.43	53	53
mol:DAG	-0.059	0.18	-10000	0	-0.52	38	38
MAP2K2	-0.12	0.25	-10000	0	-0.6	81	81
MAP2K1	-0.12	0.25	-10000	0	-0.61	79	79
EDNRA	-0.066	0.17	-10000	0	-0.55	37	37
positive regulation of muscle contraction	-0.072	0.19	-10000	0	-0.5	49	49
Gq family/GDP	-0.12	0.2	-10000	0	-0.58	51	51
HRAS/GTP	-0.1	0.21	-10000	0	-0.54	61	61
PRKCH	-0.05	0.17	-10000	0	-0.51	35	35
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.05	0.18	-10000	0	-0.55	30	30
PRKCB	-0.087	0.2	-10000	0	-0.49	64	64
PRKCE	-0.054	0.18	-10000	0	-0.55	31	31
PRKCD	-0.066	0.2	-10000	0	-0.59	42	42
PRKCG	-0.15	0.23	-10000	0	-0.51	95	95
regulation of vascular smooth muscle contraction	-0.17	0.38	-10000	0	-1	72	72
PRKCQ	-0.059	0.19	-10000	0	-0.6	33	33
PLA2G4A	-0.1	0.24	-10000	0	-0.57	72	72
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
GNA15	-0.008	0.11	-10000	0	-0.57	19	19
GNA12	0.013	0.027	-10000	0	-0.59	1	1
GNA11	0.003	0.08	-10000	0	-0.59	9	9
Rac1/GTP	-0.095	0.2	0.26	20	-0.52	50	70
MMP1	0.014	0.16	-10000	0	-0.4	48	48

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.044	0.15	0.21	1	-0.32	91	92
ACTA1	-0.066	0.18	0.22	5	-0.39	102	107
NUMA1	-0.044	0.15	0.21	1	-0.32	94	95
SPTAN1	-0.055	0.18	0.25	3	-0.39	92	95
LIMK1	-0.055	0.18	0.25	3	-0.39	92	95
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BIRC2	0.014	0	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.083	0.2	-10000	0	-0.39	140	140
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.044	0.15	0.21	1	-0.32	92	93
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.054	0.18	0.25	3	-0.38	92	95
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.063	0.18	0.25	1	-0.39	97	98
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	-0.19	0.3	-10000	0	-0.65	138	138
BID	-0.039	0.11	-10000	0	-0.24	103	103
MAP3K1	-0.014	0.069	-10000	0	-0.22	6	6
TRADD	0.013	0.027	-10000	0	-0.59	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.007	0.019	-10000	0	-0.34	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.058	0.18	0.25	3	-0.39	94	97
CASP9	0.013	0.022	-10000	0	-0.49	1	1
DNA repair	0.003	0.061	-10000	0	-0.2	18	18
neuron apoptosis	0.006	0.045	-10000	0	-0.42	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.048	0.17	0.23	2	-0.37	90	92
APAF1	0.014	0	-10000	0	-10000	0	0
CASP6	-0.029	0.12	-10000	0	-0.73	4	4
TRAF2	0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.046	0.17	0.24	3	-0.37	89	92
CASP7	0.019	0.077	0.27	38	-10000	0	38
KRT18	-0.089	0.21	-10000	0	-0.61	65	65
apoptosis	-0.07	0.18	0.26	1	-0.37	96	97
DFFA	-0.055	0.18	0.25	3	-0.39	92	95
DFFB	-0.055	0.18	0.25	3	-0.39	91	94
PARP1	-0.003	0.061	0.2	18	-10000	0	18
actin filament polymerization	0.043	0.17	0.36	85	-0.24	3	88
TNF	-0.15	0.26	-10000	0	-0.54	156	156
CYCS	-0.024	0.08	-10000	0	-0.21	37	37
SATB1	-0.025	0.12	-10000	0	-0.56	8	8
SLK	-0.057	0.18	0.25	3	-0.39	92	95
p15 BID/BAX	-0.028	0.099	-10000	0	-0.32	17	17
CASP2	-0.018	0.11	-10000	0	-0.41	13	13
JNK cascade	0.014	0.068	0.22	6	-10000	0	6
CASP3	-0.067	0.19	0.23	10	-0.41	95	105
LMNB2	-0.013	0.093	-10000	0	-0.4	9	9
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	-0.013	0.11	-10000	0	-0.5	27	27
Mammalian IAPs/DIABLO	-0.024	0.08	-10000	0	-0.32	25	25
negative regulation of DNA binding	-0.18	0.3	-10000	0	-0.64	138	138
stress fiber formation	-0.055	0.18	0.25	3	-0.38	92	95
GZMB	-0.11	0.22	-10000	0	-0.46	140	140
CASP1	-0.007	0.09	-10000	0	-0.3	41	41
LMNB1	-0.022	0.1	-10000	0	-0.4	15	15
APP	0.006	0.045	-10000	0	-0.42	1	1
TNFRSF1A	0.001	0.086	-10000	0	-0.55	12	12
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.065	-10000	0	-0.36	16	16
VIM	-0.076	0.18	0.23	6	-0.38	97	103
LMNA	-0.013	0.092	-10000	0	-0.39	9	9
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.028	0.12	-10000	0	-0.4	18	18
LRDD	0.006	0.069	-10000	0	-0.58	7	7
SREBF1	-0.065	0.18	0.24	2	-0.38	102	104
APAF-1/Caspase 9	-0.006	0.043	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.044	0.14	0.21	1	-0.31	94	95
CFL2	-0.045	0.17	0.24	2	-0.37	85	87
GAS2	-0.064	0.18	0.24	2	-0.39	98	100
positive regulation of apoptosis	-0.014	0.097	-10000	0	-0.39	10	10
PRF1	-0.062	0.19	-10000	0	-0.54	71	71

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.042	0.11	-9999	-0.3	71	71
RGS9BP	0.003	0.081	-9999	-0.57	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.012	0.023	-9999	-0.49	1	1
mol:Na +	-0.1	0.15	-9999	-0.32	161	161
mol:ADP	0.017	0.043	-9999	-0.34	7	7
GNAT2	0.01	0.032	-9999	-0.49	2	2
RGS9-1/Gbeta5/R9AP	-0.038	0.12	-9999	-0.37	53	53
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.014	0.064	-9999	-0.3	24	24
GRK7	0.006	0.054	-9999	-0.49	6	6
CNGB3	-0.01	0.094	-9999	-0.49	19	19
Cone Metarhodopsin II/X-Arrestin	-0.001	0.016	-9999	-0.35	1	1
mol:Ca2+	-0.14	0.2	-9999	-0.34	231	231
Cone PDE6	-0.044	0.11	-9999	-0.63	5	5
Cone Metarhodopsin II	-0.004	0.03	-9999	-0.26	7	7
Na + (4 Units)	-0.15	0.19	-9999	-0.34	231	231
GNAT2/GDP	-0.033	0.1	-9999	-0.33	47	47
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.067	-9999	-0.28	15	15
Cone Transducin	-0.044	0.11	-9999	-0.32	71	71
SLC24A2	-0.11	0.23	-9999	-0.55	112	112
GNB3/GNGT2	-0.057	0.14	-9999	-0.42	70	70
GNB3	-0.035	0.16	-9999	-0.57	43	43
GNAT2/GTP	-0.001	0.022	-9999	-0.35	2	2
CNGA3	-0.14	0.24	-9999	-0.53	143	143
ARR3	0.002	0.023	-9999	-0.49	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.15	-9999	-0.32	161	161
mol:Pi	-0.038	0.12	-9999	-0.37	53	53
Cone CNG Channel	-0.091	0.14	-9999	-0.37	42	42
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.23	-9999	-0.55	112	112
RGS9	-0.04	0.17	-9999	-0.58	47	47
PDE6C	0.002	0.049	-9999	-0.49	5	5
GNGT2	-0.018	0.13	-9999	-0.55	29	29
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.013	0.1	-9999	-0.49	23	23

×

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

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.11	0.17	-10000	0	-0.38	150	150
CRKL	-0.046	0.13	-10000	0	-0.28	71	71
mol:PIP3	-0.018	0.024	0.52	1	-10000	0	1
AKT1	0.003	0.027	0.36	1	-0.34	2	3
PTK2B	-0.009	0.11	-10000	0	-0.49	24	24
RAPGEF1	-0.036	0.12	-10000	0	-0.46	9	9
RANBP10	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
HGF/MET/SHIP2	-0.14	0.19	-10000	0	-0.36	203	203
MAP3K5	-0.04	0.13	-10000	0	-0.41	22	22
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.13	0.17	-10000	0	-0.39	109	109
AP1	-0.089	0.17	-10000	0	-0.4	100	100
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.009	0.05	-10000	0	-0.49	5	5
apoptosis	-0.1	0.24	-10000	0	-0.78	55	55
STAT3 (dimer)	-0.05	0.13	-10000	0	-0.42	14	14
GAB1/CRKL/SHP2/PI3K	-0.058	0.093	-10000	0	-0.43	9	9
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
CBL/CRK	-0.035	0.12	-10000	0	-0.46	9	9
PTPN11	0.014	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.027	-10000	0	-0.59	1	1
ELK1	-0.059	0.091	-10000	0	-0.2	150	150
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.048	0.071	-10000	0	-0.31	9	9
PAK1	-0.015	0.08	0.34	1	-0.31	8	9
HGF/MET/RANBP10	-0.14	0.19	-10000	0	-0.36	203	203
HRAS	-0.1	0.23	-10000	0	-0.64	66	66
DOCK1	-0.038	0.12	-10000	0	-0.46	9	9
GAB1	-0.056	0.13	-10000	0	-0.28	109	109
CRK	-0.046	0.13	-10000	0	-0.28	71	71
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.13	0.21	-10000	0	-0.58	79	79
JUN	0.003	0.075	-10000	0	-0.5	11	11
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.074	0.12	-10000	0	-0.28	109	109
PIK3R1	0.014	0	-10000	0	-10000	0	0
cell morphogenesis	-0.02	0.14	-10000	0	-0.48	8	8
GRB2/SHC	-0.052	0.12	-10000	0	-0.42	13	13
FOS	-0.094	0.22	-10000	0	-0.55	99	99
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.059	0.091	-10000	0	-0.2	150	150
HGF/MET/MUC20	-0.15	0.2	-10000	0	-0.37	203	203
cell migration	-0.052	0.12	-10000	0	-0.41	13	13
GRB2	0.013	0.022	-10000	0	-0.49	1	1
CBL	0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.11	0.17	-10000	0	-0.38	150	150
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.062	0.14	-10000	0	-0.34	39	39
MET/MUC20	-0.11	0.18	-10000	0	-0.39	150	150
RAP1B	-0.027	0.12	-10000	0	-0.41	10	10
RAP1A	-0.026	0.12	-10000	0	-0.42	9	9
HGF/MET/RANBP9	-0.14	0.19	-10000	0	-0.36	203	203
RAF1	-0.089	0.22	-10000	0	-0.59	66	66
STAT3	-0.05	0.13	-10000	0	-0.43	14	14
cell proliferation	-0.063	0.18	-10000	0	-0.39	88	88
RPS6KB1	-0.02	0.048	-10000	0	-0.16	6	6
MAPK3	-0.059	0.083	-10000	0	-10000	0	0
MAPK1	-0.059	0.083	-10000	0	-10000	0	0
RANBP9	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.024	0.14	-10000	0	-0.43	26	26
SRC	-0.05	0.13	-10000	0	-0.42	14	14
PI3K	-0.05	0.11	-10000	0	-0.4	9	9
MET/Glomulin	-0.09	0.16	-10000	0	-0.34	150	150
SOS1	0.014	0	-10000	0	-10000	0	0
MAP2K1	-0.075	0.2	-10000	0	-0.54	65	65
MET	-0.15	0.25	-10000	0	-0.53	150	150
MAP4K1	-0.046	0.14	-10000	0	-0.44	18	18
PTK2	0.014	0	-10000	0	-10000	0	0
MAP2K2	-0.075	0.2	-10000	0	-0.54	65	65
BAD	0.01	0.025	0.34	1	-0.31	2	3
MAP2K4	-0.029	0.13	-10000	0	-0.4	20	20
SHP2/GRB2/SOS1/GAB1	-0.088	0.14	-10000	0	-0.37	71	71
INPPL1	0.014	0	-10000	0	-10000	0	0
PXN	0.014	0	-10000	0	-10000	0	0
SH3KBP1	0.014	0	-10000	0	-10000	0	0
HGS	-0.06	0.12	-10000	0	-0.26	95	95
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.079	0.2	-10000	0	-0.51	91	91
RASA1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.027	-10000	0	-0.59	1	1
PTPRJ	0.013	0.022	-10000	0	-0.49	1	1
NCK/PLCgamma1	-0.049	0.12	-10000	0	-0.43	9	9
PDPK1	-0.007	0.03	0.41	1	-0.37	2	3
HGF/MET/SHIP	-0.15	0.2	-10000	0	-0.37	205	205

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.1	0.23	-9999	-0.44	127	127
MAP3K8	-0.008	0.1	-9999	-0.51	20	20
FOS	-0.089	0.2	-9999	-0.49	85	85
PRKCA	0.011	0.028	-9999	-0.6	1	1
PTPN7	-0.13	0.24	-9999	-0.55	128	128
HRAS	0.014	0.001	-9999	-10000	0	0
PRKCB	-0.063	0.19	-9999	-0.52	72	72
NRAS	0.014	0.001	-9999	-10000	0	0
RAS family/GTP	0.023	0.017	-9999	-0.25	1	1
MAPK3	-0.073	0.18	-9999	-0.46	75	75
MAP2K1	-0.016	0.12	-9999	-0.46	26	26
ELK1	0.012	0.007	-9999	-10000	0	0
BRAF	-0.052	0.13	-9999	-0.43	42	42
mol:GTP	-0.001	0.002	-9999	-0.005	95	95
MAPK1	-0.073	0.18	-9999	-0.46	76	76
RAF1	-0.037	0.1	-9999	-0.42	25	25
KRAS	0.013	0.022	-9999	-0.49	1	1

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.021	0.49	-9999	-1.1	54	54
HDAC7	0.017	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.14	0.34	-9999	-0.88	56	56
SMAD4	0.016	0.004	-9999	-10000	0	0
ID2	-0.021	0.49	-9999	-1.1	53	53
AP1	-0.065	0.18	-9999	-0.42	100	100
ABCG2	-0.022	0.49	-9999	-1.1	55	55
HIF1A	0.023	0.093	-9999	-0.62	2	2
TFF3	-0.061	0.5	-9999	-1.1	61	61
GATA2	-0.003	0.1	-9999	-0.56	16	16
AKT1	0.017	0.1	-9999	-10000	0	0
response to hypoxia	0	0.11	-9999	-0.24	14	14
MCL1	-0.021	0.49	-9999	-1.1	55	55
NDRG1	-0.026	0.5	-9999	-1.1	57	57
SERPINE1	-0.096	0.54	-9999	-1.1	79	79
FECH	-0.021	0.49	-9999	-1.1	55	55
FURIN	-0.021	0.49	-9999	-1.1	55	55
NCOA2	-0.025	0.15	-9999	-0.59	35	35
EP300	0.032	0.18	-9999	-0.35	34	34
HMOX1	-0.03	0.5	-9999	-1.1	59	59
BHLHE40	-0.029	0.5	-9999	-1.1	59	59
BHLHE41	-0.029	0.5	-9999	-1.1	58	58
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.013	0.059	-9999	-0.4	6	6
ENG	0.086	0.13	-9999	-0.52	7	7
JUN	0.003	0.075	-9999	-0.5	11	11
RORA	-0.021	0.49	-9999	-1.1	55	55
ABCB1	-0.04	0.093	-9999	-1.1	2	2
TFRC	-0.026	0.49	-9999	-1.1	60	60
CXCR4	-0.033	0.5	-9999	-1.1	59	59
TF	-0.054	0.53	-9999	-1.1	64	64
CITED2	-0.022	0.49	-9999	-1.1	55	55
HIF1A/ARNT	-0.19	0.49	-9999	-1.3	61	61
LDHA	-0.03	0.09	-9999	-0.63	7	7
ETS1	-0.026	0.49	-9999	-1.1	57	57
PGK1	-0.021	0.49	-9999	-1.1	56	56
NOS2	-0.045	0.51	-9999	-1.1	62	62
ITGB2	-0.04	0.51	-9999	-1.1	60	60
ALDOA	-0.021	0.49	-9999	-1.1	56	56
Cbp/p300/CITED2	-0.09	0.5	-9999	-1.1	56	56
FOS	-0.094	0.22	-9999	-0.55	99	99
HK2	-0.033	0.5	-9999	-1.1	59	59
SP1	0.024	0.005	-9999	-10000	0	0
GCK	-0.067	0.47	-9999	-1.1	69	69
HK1	-0.021	0.49	-9999	-1.1	55	55
NPM1	-0.021	0.49	-9999	-1.1	56	56
EGLN1	-0.021	0.49	-9999	-1.1	56	56
CREB1	0.023	0.003	-9999	-10000	0	0
PGM1	-0.021	0.49	-9999	-1.1	55	55
SMAD3	0.016	0.004	-9999	-10000	0	0
EDN1	-0.047	0.32	-9999	-0.96	32	32
IGFBP1	-0.079	0.52	-9999	-1.1	65	65
VEGFA	0.014	0.41	-9999	-0.89	40	40
HIF1A/JAB1	-0.008	0.037	-9999	-0.46	2	2
CP	-0.11	0.55	-9999	-1.1	76	76
CXCL12	-0.026	0.49	-9999	-1.1	58	58
COPS5	0.015	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0	0.004	-9999	-10000	0	0
BNIP3	-0.022	0.49	-9999	-1.1	54	54
EGLN3	-0.027	0.5	-9999	-1.1	57	57
CA9	-0.058	0.52	-9999	-1.1	66	66
TERT	-0.088	0.51	-9999	-1.1	74	74
ENO1	-0.021	0.49	-9999	-1.1	55	55
PFKL	-0.021	0.49	-9999	-1.1	55	55
NCOA1	0.015	0.001	-9999	-10000	0	0
ADM	-0.056	0.52	-9999	-1.1	66	66
ARNT	0.014	0.087	-9999	-0.65	1	1
HNF4A	-0.043	0.14	-9999	-0.49	41	41
ADFP	-0.072	0.47	-9999	-1.1	59	59
SLC2A1	0.021	0.39	-9999	-0.84	35	35
LEP	-0.056	0.48	-9999	-1.1	55	55
HIF1A/ARNT/Cbp/p300	-0.15	0.35	-9999	-0.92	57	57
EPO	0.022	0.36	-9999	-0.92	23	23
CREBBP	0.035	0.17	-9999	-0.33	31	31
HIF1A/ARNT/Cbp/p300/HDAC7	-0.14	0.34	-9999	-0.92	54	54
PFKFB3	-0.023	0.49	-9999	-1.1	56	56
NT5E	-0.028	0.5	-9999	-1.1	58	58

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.005	0.043	-10000	0	-0.45	3	3
fibroblast growth factor receptor signaling pathway	-0.005	0.043	-10000	0	-0.44	3	3
LAMA1	-0.065	0.2	-10000	0	-0.57	70	70
PRNP	0.014	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.095	0.17	-10000	0	-0.38	128	128
SMAD2	0.03	0.045	-10000	0	-0.41	2	2
GPC1/PrPc/Cu2+	-0.002	0.025	-10000	0	-0.29	4	4
GPC1/Laminin alpha1	-0.058	0.15	-10000	0	-0.41	72	72
TDGF1	-0.079	0.21	-10000	0	-0.57	82	82
CRIPTO/GPC1	-0.067	0.16	-10000	0	-0.42	83	83
APP/GPC1	-0.003	0.03	-10000	0	-0.34	4	4
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.033	0.15	-10000	0	-0.35	85	85
FLT1	0.013	0.027	-10000	0	-0.59	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.006	0.045	-10000	0	-0.32	10	10
SERPINC1	-0.004	0.087	-10000	0	-0.49	16	16
FYN	-0.03	0.14	-10000	0	-0.37	61	61
FGR	-0.032	0.14	-10000	0	-0.34	86	86
positive regulation of MAPKKK cascade	-0.073	0.19	-10000	0	-0.47	68	68
SLIT2	-0.12	0.24	-10000	0	-0.54	125	125
GPC1/NRG	-0.13	0.19	-10000	0	-0.4	165	165
NRG1	-0.17	0.27	-10000	0	-0.55	163	163
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.015	0.065	-10000	0	-0.46	2	2
LYN	-0.037	0.15	-10000	0	-0.35	91	91
mol:Spermine	0.01	0.032	-10000	0	-0.35	4	4
cell growth	-0.005	0.043	-10000	0	-0.44	3	3
BMP signaling pathway	-0.01	0.044	0.49	4	-10000	0	4
SRC	-0.03	0.14	-10000	0	-0.34	83	83
TGFBR1	0.012	0.035	-10000	0	-0.54	2	2
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.089	0.2	-10000	0	-0.51	93	93
GPC1	0.01	0.044	-10000	0	-0.49	4	4
TGFBR1 (dimer)	0.012	0.035	-10000	0	-0.54	2	2
VEGFA	-0.007	0.1	-10000	0	-0.49	22	22
BLK	-0.1	0.19	-10000	0	-0.41	95	95
HCK	-0.043	0.16	-10000	0	-0.38	76	76
FGF2	0.011	0.044	-10000	0	-0.56	3	3
FGFR1	0.013	0.027	-10000	0	-0.59	1	1
VEGFR1 homodimer	0.013	0.027	-10000	0	-0.59	1	1
TGFBR2	0.009	0.05	-10000	0	-0.49	5	5
cell death	-0.003	0.03	-10000	0	-0.34	4	4
ATIII/GPC1	-0.013	0.066	-10000	0	-0.34	20	20
PLA2G2A/GPC1	-0.068	0.14	-10000	0	-0.37	94	94
LCK	-0.089	0.19	-10000	0	-0.42	98	98
neuron differentiation	-0.13	0.19	-10000	0	-0.4	165	165
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.009	0.049	-10000	0	-0.49	5	5

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.011	0.096	-9999	-0.37	32	32
NFATC2	-0.041	0.13	-9999	-0.35	76	76
NFATC3	0.012	0.032	-9999	-0.34	2	2
CD40LG	-0.15	0.29	-9999	-0.64	102	102
PTGS2	-0.18	0.32	-9999	-0.68	118	118
JUNB	-0.033	0.15	-9999	-0.51	46	46
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.027	-9999	-0.41	2	2
CaM/Ca2+	-0.005	0.027	-9999	-0.41	2	2
CALM1	0.01	0.036	-9999	-0.55	2	2
JUN	0.001	0.075	-9999	-0.5	11	11
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-9999	-10000	0	0
FOSL1	-0.093	0.22	-9999	-0.53	101	101
CREM	0.012	0.035	-9999	-0.54	2	2
Jun/NFAT1-c-4/p21SNFT	-0.12	0.18	-9999	-0.51	65	65
FOS	-0.097	0.22	-9999	-0.56	99	99
IFNG	-0.13	0.27	-9999	-0.62	79	79
AP-1/NFAT1-c-4	-0.16	0.32	-9999	-0.7	96	96
FASLG	-0.14	0.29	-9999	-0.66	81	81
NFAT1-c-4/ICER1	-0.056	0.15	-9999	-0.44	40	40
IL2RA	-0.16	0.3	-9999	-0.66	97	97
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.13	0.26	-9999	-0.63	70	70
JunB/Fra1/NFAT1-c-4	-0.14	0.2	-9999	-0.48	97	97
IL4	-0.13	0.26	-9999	-0.63	69	69
IL2	-0.008	0.015	-9999	-10000	0	0
IL3	-0.016	0.021	-9999	-10000	0	0
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	-0.035	0.16	-9999	-0.53	46	46
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.001	-9999	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.022	0.085	-9999	-0.36	31	31
Metarhodopsin II/Arrestin	-0.029	0.092	-9999	-0.31	48	48
PDE6G/GNAT1/GTP	-0.045	0.12	-9999	-0.33	69	69
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.019	0.12	-9999	-0.5	31	31
GRK1	0.012	0.023	-9999	-0.49	1	1
CNG Channel	-0.19	0.19	-9999	-0.55	80	80
mol:Na +	-0.2	0.2	-9999	-0.52	101	101
mol:ADP	0.012	0.023	-9999	-0.49	1	1
RGS9-1/Gbeta5/R9AP	-0.038	0.12	-9999	-0.37	53	53
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.2	0.2	-9999	-0.53	101	101
CNGB1	-0.18	0.26	-9999	-0.53	179	179
RDH5	-0.019	0.12	-9999	-0.5	33	33
SAG	0.003	0.005	-9999	-10000	0	0
mol:Ca2+	-0.17	0.21	-9999	-0.49	101	101
Na + (4 Units)	-0.18	0.18	-9999	-0.48	101	101
RGS9	-0.04	0.17	-9999	-0.58	47	47
GNB1/GNGT1	-0.001	0.021	-9999	-0.34	2	2
GNAT1/GDP	-0.046	0.11	-9999	-0.33	49	49
GUCY2D	-0.006	0.087	-9999	-0.49	16	16
GNGT1	-0.001	0.031	-9999	-0.49	2	2
GUCY2F	0.005	0.05	-9999	-0.49	5	5
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.06	0.16	-9999	-0.36	72	72
mol:11-cis-retinal	-0.019	0.12	-9999	-0.5	33	33
mol:cGMP	-0.082	0.17	-9999	-0.53	29	29
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.056	0.13	-9999	-0.36	80	80
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.056	0.19	-9999	-0.56	63	63
Metarhodopsin II	-0.027	0.082	-9999	-0.28	49	49
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.11	0.17	-9999	-0.39	103	103
RGS9BP	0.003	0.081	-9999	-0.57	10	10
Metarhodopsin II/Transducin	-0.011	0.072	-9999	-0.3	13	13
GCAP Family/Ca ++	-0.1	0.16	-9999	-0.37	108	108
PDE6A/B	-0.068	0.16	-9999	-0.4	88	88
mol:Pi	-0.038	0.12	-9999	-0.37	53	53
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.017	0.067	-9999	-0.27	32	32
PDE6B	-0.034	0.16	-9999	-0.54	44	44
PDE6A	-0.038	0.16	-9999	-0.53	49	49
PDE6G	-0.032	0.16	-9999	-0.56	41	41
RHO	-0.038	0.15	-9999	-0.51	48	48
PDE6	-0.093	0.16	-9999	-0.56	30	30
GUCA1A	-0.14	0.25	-9999	-0.54	140	140
GC2/GCAP Family	-0.1	0.16	-9999	-0.38	95	95
GUCA1C	-0.012	0.089	-9999	-0.49	17	17
GUCA1B	-0.007	0.11	-9999	-0.59	18	18

×

Arf6 signaling events

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
CENTA1/KIF3B	-0.023	0.084	-9999	-0.33	35	35
ARNO/beta Arrestin1-2	-0.023	0.084	-9999	-0.53	7	7
EGFR	-0.083	0.21	-9999	-0.55	89	89
EPHA2	-0.016	0.12	-9999	-0.5	30	30
USP6	0.004	0.07	-9999	-0.49	10	10
IQSEC1	0.006	0.064	-9999	-0.5	8	8
EGFR/EGFR/EGF/EGF	-0.11	0.2	-9999	-0.43	132	132
ARRB2	0.009	0.036	-9999	-0.2	15	15
mol:GTP	0.004	0.045	-9999	-0.16	23	23
ARRB1	-0.004	0.1	-9999	-0.59	15	15
FBXO8	0.013	0.027	-9999	-0.59	1	1
TSHR	-0.2	0.27	-9999	-0.54	195	195
EGF	-0.05	0.18	-9999	-0.56	58	58
somatostatin receptor activity	0	0	-9999	-0.001	74	74
ARAP2	-0.008	0.11	-9999	-0.59	19	19
mol:GDP	-0.07	0.12	-9999	-0.28	85	85
mol:PI-3-4-5-P3	0	0	-9999	-0.001	44	44
ITGA2B	-0.043	0.17	-9999	-0.57	50	50
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.017	0.066	-9999	-0.4	3	3
ADAP1	-0.024	0.14	-9999	-0.55	35	35
KIF13B	0.014	0	-9999	-10000	0	0
HGF/MET	-0.17	0.23	-9999	-0.43	203	203
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.062	0.12	-9999	-0.28	71	71
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.097	0.17	-9999	-0.37	136	136
ADRB2	-0.015	0.13	-9999	-0.59	25	25
receptor agonist activity	0	0	-9999	0	75	75
actin filament binding	0	0	-9999	-0.001	79	79
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.052	0.18	-9999	-0.51	65	65
GNAQ	0.014	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	54	54
ARF6/GDP	-0.007	0.1	-9999	-0.41	15	15
ARF6/GDP/GULP/ACAP1	-0.11	0.16	-9999	-0.41	84	84
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.062	0.13	-9999	-0.35	54	54
ACAP1	-0.03	0.14	-9999	-0.5	44	44
ACAP2	0.013	0.027	-9999	-0.59	1	1
LHCGR/beta Arrestin2	0.002	0.05	-9999	-0.28	15	15
EFNA1	0.01	0.044	-9999	-0.49	4	4
HGF	-0.079	0.2	-9999	-0.51	91	91
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
fibronectin binding	0	0	-9999	0	76	76
endosomal lumen acidification	0	0	-9999	0	77	77
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.051	0.18	-9999	-0.57	57	57
GNAQ/ARNO	0.014	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	37	37
MET	-0.15	0.25	-9999	-0.53	150	150
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.56	19	19
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	58	58
GNA11	0.003	0.08	-9999	-0.59	9	9
LHCGR	-0.006	0.084	-9999	-0.49	15	15
AGTR1	-0.031	0.15	-9999	-0.54	41	41
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.05	-9999	-0.28	15	15
IPCEF1/ARNO	-0.058	0.14	-9999	-0.48	15	15
alphaIIb/beta3 Integrin	-0.084	0.17	-9999	-0.41	107	107

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.061	0.19	-9999	-0.58	62	62
PDGF/PDGFRA/CRKL	-0.049	0.13	-9999	-0.41	63	63
positive regulation of JUN kinase activity	-0.038	0.1	-9999	-0.32	52	52
CRKL	0.013	0.022	-9999	-0.49	1	1
PDGF/PDGFRA/Caveolin-3	-0.056	0.15	-9999	-0.42	73	73
AP1	-0.17	0.32	-9999	-0.9	73	73
mol:IP3	-0.035	0.15	-9999	-0.42	62	62
PLCG1	-0.035	0.15	-9999	-0.42	62	62
PDGF/PDGFRA/alphaV Integrin	-0.049	0.14	-9999	-0.41	62	62
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.035	0.15	-9999	-0.42	62	62
CAV3	-0.007	0.084	-9999	-0.49	15	15
CAV1	-0.05	0.17	-9999	-0.49	65	65
SHC/Grb2/SOS1	-0.037	0.11	-9999	-0.32	52	52
PDGF/PDGFRA/Shf	-0.052	0.14	-9999	-0.42	63	63
FOS	-0.13	0.34	-9999	-0.89	73	73
JUN	-0.02	0.061	-9999	-0.4	11	11
oligodendrocyte development	-0.049	0.14	-9999	-0.41	62	62
GRB2	0.013	0.022	-9999	-0.49	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
mol:DAG	-0.035	0.15	-9999	-0.42	62	62
PDGF/PDGFRA	-0.061	0.19	-9999	-0.58	62	62
actin cytoskeleton reorganization	-0.048	0.13	-9999	-0.41	62	62
SRF	0.027	0.01	-9999	-10000	0	0
SHC1	0.009	0.05	-9999	-0.49	5	5
PI3K	-0.041	0.11	-9999	-0.34	57	57
PDGF/PDGFRA/Crk/C3G	-0.04	0.11	-9999	-0.33	62	62
JAK1	-0.029	0.14	-9999	-0.41	62	62
ELK1/SRF	-0.001	0.11	-9999	-0.31	52	52
SHB	0.014	0	-9999	-10000	0	0
SHF	0.009	0.053	-9999	-0.59	4	4
CSNK2A1	0.014	0.022	-9999	-10000	0	0
GO:0007205	-0.037	0.15	-9999	-0.44	62	62
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.038	0.1	-9999	-0.32	52	52
PDGF/PDGFRA/SHB	-0.049	0.13	-9999	-0.41	62	62
PDGF/PDGFRA/Caveolin-1	-0.092	0.18	-9999	-0.41	117	117
ITGAV	0.013	0.027	-9999	-0.59	1	1
ELK1	-0.028	0.14	-9999	-0.39	56	56
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PDGF/PDGFRA/Crk	-0.049	0.13	-9999	-0.41	62	62
JAK-STAT cascade	-0.029	0.14	-9999	-0.4	62	62
cell proliferation	-0.051	0.14	-9999	-0.42	63	63

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.002	0.027	-10000	0	-0.43	2	2
Necdin/E2F1	-0.049	0.14	-10000	0	-0.41	62	62
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.078	0.14	-10000	0	-0.53	16	16
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.18	-10000	0	-0.37	148	148
NT-4/5 (dimer)/p75(NTR)	-0.065	0.15	-10000	0	-0.4	84	84
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.046	0.16	-10000	0	-0.55	16	16
IKBKG	0.014	0	-10000	0	-10000	0	0
BDNF	-0.079	0.2	-10000	0	-0.51	92	92
MGDIs/NGR/p75(NTR)/LINGO1	-0.092	0.18	-10000	0	-0.39	122	122
FURIN	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.097	0.16	-10000	0	-0.42	56	56
LINGO1	-0.019	0.14	-10000	0	-0.59	28	28
Sortilin/TRAF6/NRIF	-0.001	0.015	-10000	0	-10000	0	0
proBDNF (dimer)	-0.079	0.2	-10000	0	-0.51	92	92
NTRK1	-0.01	0.11	-10000	0	-0.52	23	23
RTN4R	-0.036	0.16	-10000	0	-0.56	45	45
neuron apoptosis	-0.063	0.17	-10000	0	-0.52	26	26
IRAK1	0.014	0	-10000	0	-10000	0	0
SHC1	-0.075	0.18	-10000	0	-0.36	139	139
ARHGDIA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.09	0.16	-10000	0	-0.37	90	90
MAGEH1	0.004	0.08	-10000	0	-0.59	9	9
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.11	0.18	-10000	0	-0.4	108	108
Mammalian IAPs/DIABLO	-0.024	0.08	-10000	0	-0.32	25	25
proNGF (dimer)	-0.074	0.21	-10000	0	-0.55	79	79
MAGED1	0.014	0	-10000	0	-10000	0	0
APP	0.014	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.01	0.088	-10000	0	-0.5	16	16
ZNF274	0.014	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.053	0.15	-10000	0	-0.34	81	81
NGF	-0.074	0.21	-10000	0	-0.55	79	79
cell cycle arrest	-0.075	0.14	-10000	0	-0.32	82	82
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.033	0.13	-10000	0	-0.44	19	19
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.055	0.12	-10000	0	-0.38	40	40
NCSTN	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.094	0.17	-10000	0	-0.36	136	136
PSENEN	0.014	0	-10000	0	-10000	0	0
mol:ceramide	-0.057	0.16	-10000	0	-0.36	82	82
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.02	0.12	-10000	0	-0.4	20	20
p75(NTR)/beta APP	-0.054	0.13	-10000	0	-0.38	72	72
BEX1	-0.007	0.11	-10000	0	-0.59	18	18
mol:GDP	-0.082	0.18	-10000	0	-0.36	136	136
NGF (dimer)	-0.13	0.18	-10000	0	-0.38	126	126
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.082	0.16	-10000	0	-0.4	80	80
PIK3R1	0.014	0	-10000	0	-10000	0	0
RAC1/GTP	-0.081	0.14	-10000	0	-0.31	136	136
MYD88	0.004	0.077	-10000	0	-0.57	9	9
CHUK	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.095	0.17	-10000	0	-0.36	136	136
RHOB	0.011	0.038	-10000	0	-0.49	3	3
RHOA	0.014	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.02	0.082	-10000	0	-0.36	28	28
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	18	18
TP53	-0.047	0.16	-10000	0	-0.51	24	24
PRDM4	-0.058	0.16	-10000	0	-0.36	82	82
BDNF (dimer)	-0.16	0.19	-10000	0	-0.44	120	120
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
SORT1	0.013	0.027	-10000	0	-0.59	1	1
activation of caspase activity	-0.077	0.14	-10000	0	-0.53	16	16
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.085	0.15	-10000	0	-0.37	83	83
RHOC	0.011	0.041	-10000	0	-0.52	3	3
XIAP	0.014	0	-10000	0	-10000	0	0
MAPK10	-0.042	0.16	-10000	0	-0.47	29	29
DIABLO	0.014	0	-10000	0	-10000	0	0
SMPD2	-0.058	0.16	-10000	0	-0.36	82	82
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.095	0.17	-10000	0	-0.36	137	137
PSEN1	0.014	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.015	-10000	0	-0.34	1	1
NT3 (dimer)/p75(NTR)	-0.066	0.15	-10000	0	-0.39	86	86
MAPK8	-0.046	0.16	-10000	0	-0.46	32	32
MAPK9	-0.041	0.16	-10000	0	-0.48	25	25
APAF1	0.014	0	-10000	0	-10000	0	0
NTF3	-0.008	0.092	-10000	0	-0.49	18	18
NTF4	-0.01	0.088	-10000	0	-0.5	16	16
NDN	-0.028	0.16	-10000	0	-0.59	36	36
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.072	0.13	-10000	0	-0.52	16	16
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.044	-10000	0	-0.36	7	7
RhoA-B-C/GTP	-0.094	0.16	-10000	0	-0.35	136	136
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.079	0.13	-10000	0	-0.52	17	17
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.087	0.14	-10000	0	-0.39	56	56
PRKACB	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.068	0.15	-10000	0	-0.37	95	95
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BIRC2	0.014	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.089	0.16	0.2	5	-0.38	88	93
BAD	-0.035	0.16	-10000	0	-0.46	26	26
RIPK2	0.014	0	-10000	0	-10000	0	0
NGFR	-0.063	0.19	-10000	0	-0.54	72	72
CYCS	-0.046	0.16	-10000	0	-0.34	82	82
ADAM17	0.007	0.065	-10000	0	-0.59	6	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.085	0.15	-10000	0	-0.37	82	82
BCL2L11	-0.036	0.16	-10000	0	-0.46	26	26
BDNF (dimer)/p75(NTR)	-0.12	0.19	-10000	0	-0.4	148	148
PI3K	-0.084	0.15	-10000	0	-0.37	81	81
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.085	0.15	-10000	0	-0.37	82	82
NDNL2	0.014	0	-10000	0	-10000	0	0
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKCI	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.11	0.2	-10000	0	-0.43	136	136
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.085	0.15	-10000	0	-0.37	82	82
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
PLG	-0.001	0.038	-10000	0	-0.49	3	3
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.092	0.18	-10000	0	-0.46	61	61
SQSTM1	0.014	0	-10000	0	-10000	0	0
NGFRAP1	0.014	0	-10000	0	-10000	0	0
CASP3	-0.03	0.15	-10000	0	-0.41	28	28
E2F1	-0.015	0.12	-10000	0	-0.51	28	28
CASP9	0.013	0.022	-10000	0	-0.49	1	1
IKK complex	-0.067	0.12	-10000	0	-0.5	19	19
NGF (dimer)/TRKA	-0.077	0.16	-10000	0	-0.4	98	98
MMP7	-0.15	0.25	-10000	0	-0.54	152	152
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.078	0.14	-10000	0	-0.53	17	17
MMP3	-0.037	0.14	-10000	0	-0.49	46	46
APAF-1/Caspase 9	-0.068	0.11	-10000	0	-0.43	24	24

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.041	0.095	0.2	126	-10000	0	126
BUB1B	-0.059	0.14	-10000	0	-0.3	124	124
PLK1	-0.001	0.043	-10000	0	-0.14	27	27
PLK1S1	0.006	0.022	-10000	0	-0.11	2	2
KIF2A	0.006	0.048	-10000	0	-0.3	5	5
regulation of mitotic centrosome separation	-0.001	0.043	-10000	0	-0.13	27	27
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.13	0.24	-10000	0	-0.43	180	180
WEE1	-0.007	0.088	-10000	0	-0.37	19	19
cytokinesis	-0.11	0.21	-10000	0	-0.42	136	136
PP2A-alpha B56	-0.061	0.22	-10000	0	-0.67	59	59
AURKA	0.001	0.041	-10000	0	-0.15	23	23
PICH/PLK1	-0.031	0.16	-10000	0	-0.43	62	62
CENPE	-0.045	0.14	-10000	0	-0.32	94	94
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.006	0.047	-10000	0	-0.3	5	5
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	-0.02	0.081	-10000	0	-0.2	73	73
PAK1	-0.035	0.15	-10000	0	-0.5	49	49
SPC24	-0.12	0.24	-10000	0	-0.53	128	128
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	-0.037	0.1	-10000	0	-0.26	78	78
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.004	0.009	4	-0.013	37	41
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0	0.022	-10000	0	-0.067	26	26
G2 phase of mitotic cell cycle	0	0.002	0.009	1	-0.009	28	29
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.003	0.01	-10000	0	-10000	0	0
spindle elongation	-0.001	0.043	-10000	0	-0.13	27	27
ODF2	0.013	0.003	-10000	0	-10000	0	0
BUB1	-0.1	0.24	-10000	0	-0.74	59	59
TPT1	0.006	0.022	-10000	0	-0.13	1	1
CDC25C	-0.05	0.13	-10000	0	-0.32	89	89
CDC25B	0.014	0.003	-10000	0	-10000	0	0
SGOL1	-0.041	0.095	-10000	0	-0.2	126	126
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.029	0.089	-10000	0	-0.33	30	30
CDC14B	0.012	0.001	-10000	0	-10000	0	0
CDC20	-0.11	0.23	-10000	0	-0.54	112	112
PLK1/PBIP1	-0.048	0.11	-10000	0	-0.32	70	70
mitosis	0.001	0.005	0.021	9	-0.022	1	10
FBXO5	0.004	0.05	-10000	0	-0.28	8	8
CDC2	0	0.004	-10000	0	-0.014	38	38
NDC80	-0.13	0.25	-10000	0	-0.55	134	134
metaphase plate congression	0.005	0.026	-10000	0	-0.14	2	2
ERCC6L	-0.056	0.14	-10000	0	-0.44	55	55
NLP/gamma Tubulin	0.003	0.025	-10000	0	-0.11	3	3
microtubule cytoskeleton organization	0.006	0.022	-10000	0	-0.13	1	1
G2/M transition DNA damage checkpoint	0	0.002	0.01	5	-10000	0	5
PPP1R12A	0.013	0.027	-10000	0	-0.59	1	1
interphase	0	0.002	0.01	5	-10000	0	5
PLK1/PRC1-2	-0.09	0.18	-10000	0	-0.34	168	168
GRASP65/GM130/RAB1/GTP/PLK1	-0.005	0.023	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.036	-10000	0	-0.2	2	2
mitotic prometaphase	-0.001	0.002	-10000	0	-0.009	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.061	-10000	0	-10000	0	0
microtubule-based process	-0.093	0.17	-10000	0	-0.33	168	168
Golgi organization	-0.001	0.043	-10000	0	-0.13	27	27
Cohesin/SA2	-0.012	0.029	-10000	0	-0.22	2	2
PPP1CB/MYPT1	0.003	0.021	-10000	0	-0.43	1	1
KIF20A	-0.17	0.26	-10000	0	-0.55	168	168
APC/C/CDC20	-0.058	0.15	-10000	0	-0.33	112	112
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.047	0.11	-10000	0	-0.32	70	70
PRC1	-0.005	0.098	-10000	0	-0.49	20	20
ECT2	-0.003	0.081	-10000	0	-0.35	22	22
C13orf34	0.006	0.036	-10000	0	-0.21	2	2
NUDC	0.005	0.026	-10000	0	-0.14	2	2
regulation of attachment of spindle microtubules to kinetochore	-0.058	0.14	-10000	0	-0.3	124	124
spindle assembly	0.002	0.035	-10000	0	-0.1	25	25
spindle stabilization	0.006	0.022	-10000	0	-0.11	2	2
APC/C/HCDH1	0.02	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	-0.094	0.17	-10000	0	-0.33	168	168
CCNB1	-0.019	0.13	-10000	0	-0.49	34	34
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	-0.006	0.095	-10000	0	-0.44	21	21
TUBG1	0.006	0.022	-10000	0	-0.13	1	1
G2/M transition of mitotic cell cycle	-0.031	0.087	-10000	0	-0.33	30	30
MLF1IP	-0.043	0.14	-10000	0	-0.4	70	70
INCENP	0.011	0.027	-10000	0	-0.6	1	1

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.019	0.11	-10000	0	-0.88	4	4
SMARCC2	0.015	0.01	-10000	0	-10000	0	0
SMARCC1	0.015	0.01	-10000	0	-10000	0	0
TBX21	-0.11	0.25	-10000	0	-0.71	60	60
SUMO2	0.013	0.014	-10000	0	-10000	0	0
STAT1 (dimer)	0	0.11	-10000	0	-0.59	16	16
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	-0.089	0.22	-10000	0	-0.56	92	92
GR alpha/HSP90/FKBP51/HSP90	0.02	0.16	0.29	25	-0.33	42	67
PRL	-0.044	0.09	-10000	0	-0.53	1	1
cortisol/GR alpha (dimer)/TIF2	0.18	0.24	0.51	113	-0.42	10	123
RELA	-0.063	0.097	-10000	0	-0.29	3	3
FGG	0.16	0.17	0.47	49	-0.48	2	51
GR beta/TIF2	0.063	0.16	0.31	34	-0.4	34	68
IFNG	-0.23	0.21	-10000	0	-0.62	60	60
apoptosis	-0.009	0.2	0.64	18	-0.7	2	20
CREB1	0.013	0.023	-10000	0	-10000	0	0
histone acetylation	-0.044	0.12	-10000	0	-0.37	33	33
BGLAP	-0.046	0.12	-10000	0	-0.55	11	11
GR/PKAc	0.087	0.093	0.29	27	-10000	0	27
NF kappa B1 p50/RelA	-0.11	0.18	-10000	0	-0.42	69	69
SMARCD1	0.015	0.01	-10000	0	-10000	0	0
MDM2	0.079	0.077	0.27	28	-10000	0	28
GATA3	-0.1	0.23	-10000	0	-0.53	115	115
AKT1	0.002	0.018	-10000	0	-10000	0	0
CSF2	-0.061	0.099	-10000	0	-0.52	2	2
GSK3B	0.012	0.03	-10000	0	-0.6	1	1
NR1I3	0.028	0.19	0.64	15	-0.68	3	18
CSN2	0.14	0.13	0.4	27	-10000	0	27
BRG1/BAF155/BAF170/BAF60A	0.039	0.036	-10000	0	-0.29	1	1
NFATC1	-0.02	0.14	-10000	0	-0.57	31	31
POU2F1	0.015	0.007	-10000	0	-10000	0	0
CDKN1A	-0.063	0.32	-10000	0	-1.5	21	21
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.012	-10000	0	-10000	0	0
SFN	-0.11	0.23	-10000	0	-0.53	117	117
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.041	0.19	0.29	11	-0.42	42	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.052	0.32	0.61	15	-0.81	54	69
JUN	-0.16	0.19	-10000	0	-0.49	75	75
IL4	-0.081	0.15	-10000	0	-0.59	19	19
CDK5R1	-0.022	0.14	-10000	0	-0.59	30	30
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.2	0.2	1	-0.47	122	123
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.029	0.15	0.29	20	-0.32	16	36
cortisol/GR alpha (monomer)	0.23	0.26	0.59	127	-10000	0	127
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.23	-10000	0	-0.59	99	99
AP-1/NFAT1-c-4	-0.31	0.3	-10000	0	-0.68	149	149
AFP	-0.12	0.17	-10000	0	-0.64	19	19
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.11	0.15	0.44	17	-0.46	6	23
TP53	-0.014	0.15	-10000	0	-0.53	34	34
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.43	0.48	-10000	0	-1	177	177
KRT14	-0.12	0.18	-10000	0	-0.54	38	38
TBP	0.023	0.016	-10000	0	-10000	0	0
CREBBP	0.031	0.059	-10000	0	-10000	0	0
HDAC1	0.004	0.054	-10000	0	-0.59	4	4
HDAC2	0.014	0.001	-10000	0	-10000	0	0
AP-1	-0.31	0.31	-10000	0	-0.68	150	150
MAPK14	0.013	0.011	-10000	0	-10000	0	0
MAPK10	0.008	0.055	-10000	0	-0.59	4	4
MAPK11	0.002	0.08	-10000	0	-0.59	9	9
KRT5	-0.4	0.44	-10000	0	-0.9	177	177
interleukin-1 receptor activity	0	0.001	-10000	0	-10000	0	0
NCOA1	0.017	0.01	-10000	0	-10000	0	0
STAT1	0	0.11	-10000	0	-0.59	16	16
CGA	-0.064	0.12	-10000	0	-0.47	13	13
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.081	0.11	0.36	15	-10000	0	15
MAPK3	0.013	0.012	-10000	0	-10000	0	0
MAPK1	0.013	0.011	-10000	0	-10000	0	0
ICAM1	-0.2	0.28	-10000	0	-0.72	75	75
NFKB1	-0.063	0.097	-10000	0	-0.28	8	8
MAPK8	-0.13	0.17	-10000	0	-0.44	73	73
MAPK9	0.013	0.011	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.012	0.2	0.64	18	-0.74	2	20
BAX	0.001	0.11	-10000	0	-10000	0	0
POMC	-0.13	0.24	-10000	0	-1.3	13	13
EP300	0.026	0.079	-10000	0	-0.57	4	4
cortisol/GR alpha (dimer)/p53	0.18	0.23	0.49	116	-0.67	1	117
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.068	0.25	18	-10000	0	18
SGK1	0.052	0.24	-10000	0	-1.4	13	13
IL13	-0.23	0.24	-10000	0	-0.67	73	73
IL6	-0.28	0.38	-10000	0	-0.8	140	140
PRKACG	0.005	0.044	-10000	0	-0.49	4	4
IL5	-0.2	0.19	-10000	0	-0.63	36	36
IL2	-0.23	0.21	-10000	0	-0.61	61	61
CDK5	0.014	0.006	-10000	0	-10000	0	0
PRKACB	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.32	0.41	-10000	0	-0.9	143	143
CDK5R1/CDK5	-0.02	0.1	-10000	0	-0.43	30	30
NF kappa B1 p50/RelA/PKAc	-0.055	0.13	-10000	0	-0.39	8	8
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.49	119	-10000	0	119
SMARCA4	0.015	0.01	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.13	0.37	55	-0.35	3	58
NF kappa B1 p50/RelA/Cbp	-0.052	0.16	-10000	0	-0.46	14	14
JUN (dimer)	-0.16	0.19	-10000	0	-0.49	75	75
YWHAH	-0.009	0.11	-10000	0	-0.49	24	24
VIPR1	-0.12	0.26	-10000	0	-0.68	79	79
NR3C1	0.14	0.14	0.42	62	-10000	0	62
NR4A1	-0.021	0.14	-10000	0	-0.5	39	39
TIF2/SUV420H1	-0.029	0.11	-10000	0	-0.43	35	35
MAPKKK cascade	-0.009	0.2	0.64	18	-0.7	2	20
cortisol/GR alpha (dimer)/Src-1	0.21	0.21	0.51	123	-10000	0	123
PBX1	0.014	0.028	-10000	0	-0.59	1	1
POU1F1	0.004	0.024	-10000	0	-0.49	1	1
SELE	-0.27	0.36	-10000	0	-0.8	124	124
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.13	0.37	55	-0.35	3	58
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.49	119	-10000	0	119
mol:cortisol	0.12	0.15	0.33	130	-10000	0	130
MMP1	-0.11	0.15	-10000	0	-0.53	45	45

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.017	0.12	-9999	-0.5	31	31
PLK4	-0.013	0.12	-9999	-0.51	27	27
regulation of centriole replication	-0.018	0.12	-9999	-0.36	57	57

×

Osteopontin-mediated 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
IKK alpha homodimer	-0.036	0.16	-9999	-0.49	25	25
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.16	-9999	-0.46	24	24
alphaV/beta3 Integrin/Osteopontin/Src	-0.068	0.15	-9999	-0.38	92	92
AP1	-0.08	0.22	-9999	-0.6	46	46
ILK	-0.045	0.17	-9999	-0.51	24	24
bone resorption	-0.078	0.23	-9999	-0.53	79	79
PTK2B	-0.009	0.11	-9999	-0.49	24	24
PYK2/p130Cas	-0.094	0.16	-9999	-0.51	42	42
ITGAV	0.016	0.027	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.067	0.16	-9999	-0.42	83	83
alphaV/beta3 Integrin/Osteopontin	-0.094	0.16	-9999	-0.39	102	102
MAP3K1	-0.05	0.17	-9999	-0.5	31	31
JUN	0.003	0.075	-9999	-0.5	11	11
MAPK3	-0.039	0.17	-9999	-0.5	28	28
MAPK1	-0.039	0.17	-9999	-0.43	46	46
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.045	0.18	-9999	-0.5	35	35
ITGB3	-0.05	0.18	-9999	-0.51	65	65
NFKBIA	-0.029	0.17	-9999	-0.5	26	26
FOS	-0.094	0.22	-9999	-0.55	99	99
CD44	-0.058	0.19	-9999	-0.55	65	65
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.067	0.27	-9999	-0.73	51	51
NF kappa B1 p50/RelA	-0.074	0.13	-9999	-0.52	18	18
BCAR1	0.013	0.027	-9999	-0.59	1	1
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.047	0.12	-9999	-0.36	66	66
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.061	0.19	-9999	-0.55	43	43
VAV3	-0.12	0.23	-9999	-0.56	72	72
MAP3K14	-0.048	0.17	-9999	-0.42	48	48
ROCK2	-0.011	0.12	-9999	-0.59	21	21
SPP1	-0.081	0.21	-9999	-0.53	91	91
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.19	-9999	-0.52	71	71
MMP2	-0.067	0.21	-9999	-0.6	35	35

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.003	0.03	-10000	0	-0.34	4	4
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.013	0.022	-10000	0	-0.49	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.078	0.12	-10000	0	-0.4	29	29
IRAK/TOLLIP	0.03	0.025	-10000	0	-10000	0	0
IKBKB	0.014	0	-10000	0	-10000	0	0
IKBKG	0.014	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.17	0.21	-10000	0	-0.41	208	208
IL1A	-0.093	0.22	-10000	0	-0.54	99	99
IL1B	-0.13	0.21	-10000	0	-0.4	189	189
IRAK/TRAF6/p62/Atypical PKCs	-0.014	0.057	-10000	0	-0.42	1	1
IL1R2	-0.12	0.24	-10000	0	-0.53	130	130
IL1R1	-0.031	0.15	-10000	0	-0.52	44	44
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.045	0.12	0.21	1	-0.43	19	20
TOLLIP	0.014	0	-10000	0	-10000	0	0
TICAM2	0	0.089	-10000	0	-0.57	12	12
MAP3K3	0.014	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.064	0.033	-10000	0	-10000	0	0
JUN	0.034	0.069	-10000	0	-0.45	4	4
MAP3K7	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.14	0.17	-10000	0	-0.54	48	48
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.11	0.17	-10000	0	-0.4	87	87
PIK3R1	0.014	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.099	0.16	-10000	0	-0.54	28	28
IL1 beta fragment/IL1R1/IL1RAP	-0.14	0.21	-10000	0	-0.43	118	118
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.033	0.058	-10000	0	-0.54	1	1
IRAK1	0.023	0.027	-10000	0	-0.28	4	4
IL1RN/IL1R1	-0.12	0.2	-10000	0	-0.42	143	143
IRAK4	0.013	0.022	-10000	0	-0.49	1	1
PRKCI	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.063	0.14	-10000	0	-0.45	28	28
CHUK	0.014	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.14	0.21	-10000	0	-0.43	118	118
IL1 beta/IL1R2	-0.19	0.23	-10000	0	-0.38	267	267
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.022	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.15	-10000	0	-0.48	48	48
IRAK3	0.007	0.062	-10000	0	-0.56	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.14	0.18	-10000	0	-0.54	55	55
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.043	0.14	-10000	0	-0.57	11	11
IL1 alpha/IL1R1/IL1RAP	-0.12	0.18	-10000	0	-0.44	81	81
RELA	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.014	0	-10000	0	-10000	0	0
MYD88	0.004	0.077	-10000	0	-0.57	9	9
IRAK/TRAF6/MEKK3	0.037	0.027	-10000	0	-10000	0	0
IL1RAP	-0.037	0.16	-10000	0	-0.51	50	50
UBE2N	0.014	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.11	0.15	-10000	0	-0.45	56	56
CASP1	-0.016	0.12	-10000	0	-0.53	28	28
IL1RN/IL1R2	-0.18	0.24	-10000	0	-0.45	202	202
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.13	0.21	-10000	0	-0.57	51	51
TMEM189-UBE2V1	0.004	0.044	-10000	0	-0.49	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.024	0.12	-10000	0	-0.4	23	23
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
IL1RN	-0.11	0.23	-10000	0	-0.53	118	118
TRAF6/TAK1/TAB1/TAB2	-0.002	0.023	-10000	0	-0.29	1	1
MAP2K6	0.033	0.029	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.063	0.13	-10000	0	-0.3	113	113
regulation of S phase of mitotic cell cycle	-0.02	0.11	-10000	0	-0.26	71	71
GNAO1	0.008	0.06	-10000	0	-0.59	5	5
HRAS	0.014	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.007	0.055	-10000	0	-0.36	12	12
PELP1	0.014	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.025	0.12	-10000	0	-0.36	23	23
T-DHT/AR	-0.086	0.17	-10000	0	-0.41	109	109
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.006	95	95
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
mol:GDP	-0.078	0.16	-10000	0	-0.46	71	71
cell proliferation	-0.038	0.18	-10000	0	-0.41	62	62
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
FOS	-0.085	0.28	-10000	0	-0.78	62	62
mol:Ca2+	-0.011	0.019	-10000	0	-0.069	17	17
MAPK3	-0.03	0.15	-10000	0	-0.44	26	26
MAPK1	-0.014	0.089	-10000	0	-0.27	19	19
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.004	99	99
cAMP biosynthetic process	0.002	0.055	-10000	0	-0.33	12	12
GNG2	0.009	0.053	-10000	0	-0.59	4	4
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	99	99
HRAS/GTP	-0.059	0.11	-10000	0	-0.29	78	78
actin cytoskeleton reorganization	-0.001	0.012	-10000	0	-0.28	1	1
SRC	0.014	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	99	99
PI3K	0.001	0.017	-10000	0	-0.36	1	1
apoptosis	0.037	0.16	0.42	62	-10000	0	62
T-DHT/AR/PELP1	-0.071	0.14	-10000	0	-0.34	109	109
HRAS/GDP	-0.071	0.15	-10000	0	-0.43	71	71
CREB1	-0.041	0.18	-10000	0	-0.45	62	62
RAC1-CDC42/GTP	-0.001	0.013	-10000	0	-0.28	1	1
AR	-0.11	0.24	-10000	0	-0.56	109	109
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.029	0.12	-10000	0	-0.28	75	75
RAC1-CDC42/GDP	-0.066	0.14	-10000	0	-0.4	71	71
T-DHT/AR/PELP1/Src	-0.063	0.13	-10000	0	-0.3	109	109
MAP2K2	-0.024	0.12	-10000	0	-0.34	23	23
T-DHT/AR/PELP1/Src/PI3K	-0.02	0.11	-10000	0	-0.26	71	71
GNAZ	0.014	0	-10000	0	-10000	0	0
SHBG	0	0.089	-10000	0	-0.57	12	12
Gi family/GNB1/GNG2/GDP	0.021	0.075	-10000	0	-0.45	6	6
mol:T-DHT	0	0.001	-10000	0	-0.003	72	72
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	0.001	0.067	-10000	0	-0.4	14	14
Gi family/GTP	-0.014	0.081	-10000	0	-0.36	7	7
CDC42	0.014	0	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.051	0.12	-9999	-0.34	54	54
NF kappa B1 p50/RelA/I kappa B alpha	-0.041	0.089	-9999	-0.39	14	14
AP1	-0.12	0.17	-9999	-0.46	66	66
mol:PIP3	-0.097	0.15	-9999	-0.46	45	45
AKT1	0.019	0.098	-9999	-0.34	10	10
PTK2B	-0.018	0.1	-9999	-0.31	34	34
RHOA	0.008	0.063	-9999	-0.32	7	7
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.006	0.086	-9999	-0.37	9	9
MAGI3	0.002	0.084	-9999	-0.59	10	10
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.042	0.13	-9999	-0.34	60	60
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.006	0.1	-9999	-0.33	24	24
NF kappa B1 p50/RelA	-0.068	0.13	-9999	-0.49	26	26
endothelial cell migration	-0.045	0.18	-9999	-0.44	72	72
ADCY4	-0.022	0.15	-9999	-0.41	56	56
ADCY5	-0.027	0.16	-9999	-0.42	63	63
ADCY6	-0.019	0.15	-9999	-0.41	55	55
ADCY7	-0.019	0.15	-9999	-0.41	55	55
ADCY1	-0.047	0.17	-9999	-0.43	64	64
ADCY2	-0.025	0.16	-9999	-0.42	59	59
ADCY3	-0.019	0.15	-9999	-0.41	55	55
ADCY8	-0.043	0.18	-9999	-0.48	61	61
ADCY9	-0.021	0.15	-9999	-0.41	55	55
GSK3B	-0.009	0.1	-9999	-0.32	25	25
arachidonic acid secretion	-0.012	0.14	-9999	-0.38	55	55
GNG2	0.009	0.053	-9999	-0.59	4	4
TRIP6	0.009	0.065	-9999	-0.37	6	6
GNAO1	-0.033	0.14	-9999	-0.35	80	80
HRAS	0.014	0	-9999	-10000	0	0
NFKBIA	-0.011	0.12	-9999	-0.41	25	25
GAB1	0.012	0.035	-9999	-0.54	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.082	-9999	-1	3	3
JUN	0.003	0.075	-9999	-0.5	11	11
LPA/LPA2/NHERF2	-0.011	0.054	-9999	-0.33	13	13
TIAM1	-0.006	0.11	-9999	-1.3	3	3
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.006	0.088	-9999	-0.38	9	9
PLCB3	0.019	0.053	-9999	-0.32	8	8
FOS	-0.094	0.22	-9999	-0.55	99	99
positive regulation of mitosis	-0.012	0.14	-9999	-0.38	55	55
LPA/LPA1-2-3	-0.079	0.14	-9999	-0.37	72	72
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.013	0.027	-9999	-0.59	1	1
stress fiber formation	-0.021	0.12	-9999	-0.34	33	33
GNAZ	-0.03	0.14	-9999	-0.34	76	76
EGFR/PI3K-beta/Gab1	-0.1	0.15	-9999	-0.48	45	45
positive regulation of dendritic cell cytokine production	-0.079	0.14	-9999	-0.36	72	72
LPA/LPA2/MAGI-3	-0.017	0.07	-9999	-0.35	21	21
ARHGEF1	-0.009	0.12	-9999	-0.31	51	51
GNAI2	-0.03	0.14	-9999	-0.34	76	76
GNAI3	-0.03	0.14	-9999	-0.34	76	76
GNAI1	-0.042	0.15	-9999	-0.35	92	92
LPA/LPA3	-0.037	0.11	-9999	-0.36	49	49
LPA/LPA2	-0.013	0.062	-9999	-0.41	11	11
LPA/LPA1	-0.066	0.15	-9999	-0.38	89	89
HB-EGF/EGFR	-0.13	0.21	-9999	-0.37	201	201
HBEGF	-0.093	0.19	-9999	-0.38	148	148
mol:DAG	0.006	0.088	-9999	-0.38	9	9
cAMP biosynthetic process	-0.023	0.16	-9999	-0.42	55	55
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	-0.015	0.13	-9999	-0.42	28	28
GNAQ	-0.008	0.084	-9999	-0.32	17	17
LPAR2	0.002	0.084	-9999	-0.56	11	11
LPAR3	-0.041	0.15	-9999	-0.49	49	49
LPAR1	-0.065	0.2	-9999	-0.56	68	68
IL8	-0.18	0.23	-9999	-0.48	157	157
PTK2	-0.044	0.15	-9999	-0.34	67	67
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.042	0.13	-9999	-0.34	60	60
EGFR	-0.084	0.21	-9999	-0.55	89	89
PLCG1	-0.009	0.09	-9999	-0.3	23	23
PLD2	-0.045	0.15	-9999	-0.35	67	67
G12/G13	-0.049	0.11	-9999	-0.34	51	51
PI3K-beta	-0.038	0.086	-9999	-0.38	12	12
cell migration	-0.026	0.055	-9999	-0.23	11	11
SLC9A3R2	0.012	0.031	-9999	-0.49	2	2
PXN	-0.021	0.12	-9999	-0.34	33	33
HRAS/GTP	-0.013	0.15	-9999	-0.39	55	55
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.14	0.24	-9999	-0.52	144	144
PRKCE	0.003	0.077	-9999	-0.52	11	11
PRKCD	-0.003	0.11	-9999	-0.39	21	21
Gi(beta/gamma)	-0.014	0.14	-9999	-0.38	56	56
mol:LPA	-0.003	0.035	-9999	-0.19	8	8
TRIP6/p130 Cas/FAK1/Paxillin	-0.065	0.12	-9999	-0.43	25	25
MAPKKK cascade	-0.012	0.14	-9999	-0.38	55	55
contractile ring contraction involved in cytokinesis	0.008	0.062	-9999	-0.31	7	7
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.022	0.1	-9999	-0.32	35	35
GNA15	-0.019	0.099	-9999	-0.31	33	33
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.007	0.11	-9999	-0.34	24	24
GNA11	-0.014	0.094	-9999	-0.32	26	26
Rac1/GTP	-0.003	0.09	-9999	-1.1	3	3
MMP2	-0.045	0.18	-9999	-0.44	72	72

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.037	0.14	-10000	0	-0.36	50	50
IKBKB	-0.012	0.078	-10000	0	-0.26	15	15
AKT1	-0.049	0.1	-10000	0	-0.25	47	47
IKBKG	-0.01	0.083	-10000	0	-0.28	17	17
CALM1	-0.055	0.15	-10000	0	-0.41	57	57
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
MAP3K1	-0.061	0.18	-10000	0	-0.49	56	56
MAP3K7	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.066	0.16	0.21	2	-0.44	57	59
DOK1	0.012	0.035	-10000	0	-0.54	2	2
AP-1	-0.034	0.099	0.18	2	-0.25	40	42
LYN	0.004	0.073	-10000	0	-0.51	10	10
BLNK	-0.056	0.19	-10000	0	-0.57	61	61
SHC1	0.009	0.05	-10000	0	-0.49	5	5
BCR complex	-0.076	0.18	-10000	0	-0.44	91	91
CD22	-0.17	0.21	-10000	0	-0.51	96	96
CAMK2G	-0.044	0.14	-10000	0	-0.45	36	36
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	0.008	0.06	-10000	0	-0.54	6	6
SHC/GRB2/SOS1	-0.091	0.17	-10000	0	-0.55	43	43
GO:0007205	-0.067	0.16	0.21	2	-0.44	57	59
SYK	-0.013	0.12	-10000	0	-0.57	24	24
ELK1	-0.055	0.15	-10000	0	-0.41	57	57
NFATC1	-0.062	0.17	-10000	0	-0.45	62	62
B-cell antigen/BCR complex	-0.076	0.18	-10000	0	-0.44	91	91
PAG1/CSK	-0.001	0.019	-10000	0	-0.43	1	1
NFKBIB	0.006	0.029	0.081	2	-10000	0	2
HRAS	-0.049	0.16	-10000	0	-0.41	56	56
NFKBIA	0.007	0.028	0.081	2	-10000	0	2
NF-kappa-B/RelA/I kappa B beta	0.013	0.023	-10000	0	-10000	0	0
RasGAP/Csk	-0.12	0.18	-10000	0	-0.55	51	51
mol:GDP	-0.062	0.16	-10000	0	-0.42	57	57
PTEN	0.013	0.027	-10000	0	-0.59	1	1
CD79B	-0.048	0.17	-10000	0	-0.53	58	58
NF-kappa-B/RelA/I kappa B alpha	0.013	0.023	-10000	0	-10000	0	0
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PI3K/BCAP/CD19	-0.086	0.19	-10000	0	-0.48	73	73
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.068	0.16	0.21	2	-0.45	57	59
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.095	0.18	-10000	0	-0.5	54	54
CHUK	-0.01	0.083	-10000	0	-0.28	17	17
IBTK	0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.064	0.14	-10000	0	-0.51	35	35
PTPN6	-0.16	0.21	-10000	0	-0.53	89	89
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	-0.005	0.045	-10000	0	-0.1	31	31
VAV2	-0.11	0.18	-10000	0	-0.52	62	62
ubiquitin-dependent protein catabolic process	0.011	0.028	0.085	2	-10000	0	2
BTK	-0.041	0.2	0.36	1	-1.1	17	18
CD19	-0.11	0.18	-10000	0	-0.5	69	69
MAP4K1	-0.018	0.14	-10000	0	-0.58	28	28
CD72	-0.008	0.11	-10000	0	-0.51	22	22
PAG1	0.013	0.027	-10000	0	-0.59	1	1
MAPK14	-0.044	0.16	-10000	0	-0.42	49	49
SH3BP5	0.01	0.051	-10000	0	-0.57	4	4
PIK3AP1	-0.065	0.18	0.24	2	-0.48	64	66
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.066	0.22	-10000	0	-0.54	64	64
RAF1	-0.039	0.15	-10000	0	-0.44	38	38
RasGAP/p62DOK/SHIP	-0.12	0.18	-10000	0	-0.54	53	53
CD79A	-0.04	0.16	-10000	0	-0.54	50	50
re-entry into mitotic cell cycle	-0.034	0.099	0.18	2	-0.25	40	42
RASA1	0.014	0	-10000	0	-10000	0	0
MAPK3	-0.017	0.12	-10000	0	-0.41	25	25
MAPK1	-0.017	0.12	-10000	0	-0.41	25	25
CD72/SHP1	-0.14	0.22	-10000	0	-0.53	88	88
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.051	0.16	-10000	0	-0.42	58	58
actin cytoskeleton organization	-0.063	0.17	-10000	0	-0.45	56	56
NF-kappa-B/RelA	0.03	0.045	0.16	2	-10000	0	2
Calcineurin	-0.057	0.12	-10000	0	-0.44	31	31
PI3K	-0.13	0.17	-10000	0	-0.47	79	79
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.081	0.17	0.24	2	-0.49	57	59
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.27	-10000	0	-0.79	58	58
DAPP1	-0.14	0.29	-10000	0	-0.88	55	55
cytokine secretion	-0.057	0.16	-10000	0	-0.42	62	62
mol:DAG	-0.068	0.16	0.21	2	-0.45	57	59
PLCG2	0	0.088	-10000	0	-0.55	13	13
MAP2K1	-0.028	0.14	-10000	0	-0.45	28	28
B-cell antigen/BCR complex/FcgammaRIIB	-0.15	0.22	-10000	0	-0.41	185	185
mol:PI-3-4-5-P3	-0.099	0.12	-10000	0	-0.35	61	61
ETS1	-0.038	0.14	-10000	0	-0.43	33	33
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.1	0.2	-10000	0	-0.63	41	41
B-cell antigen/BCR complex/LYN	-0.1	0.18	-10000	0	-0.47	76	76
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.013	0.027	-10000	0	-0.59	1	1
RAC1	-0.068	0.18	-10000	0	-0.49	55	55
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.23	-10000	0	-0.57	91	91
CARD11	-0.066	0.18	-10000	0	-0.49	60	60
FCGR2B	-0.13	0.24	-10000	0	-0.53	138	138
PPP3CA	0.012	0.031	-10000	0	-0.49	2	2
BCL10	0.014	0	-10000	0	-10000	0	0
IKK complex	0.002	0.036	-10000	0	-0.12	1	1
PTPRC	-0.041	0.17	-10000	0	-0.54	51	51
PDPK1	-0.049	0.098	-10000	0	-0.25	42	42
PPP3CB	0.011	0.038	-10000	0	-0.49	3	3
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.013	0.024	-10000	0	-0.099	7	7

×

EGFR-dependent Endothelin 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
HRAS	0.014	0	-9999	-10000	0	0
EGFR	-0.083	0.21	-9999	-0.55	89	89
EGF/EGFR	-0.11	0.17	-9999	-0.36	118	118
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.078	0.14	-9999	-0.53	17	17
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.02	0.14	-9999	-0.54	32	32
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.05	0.18	-9999	-0.56	58	58
EGF/EGFR dimer/SHC	-0.095	0.17	-9999	-0.36	135	135
mol:GDP	-0.078	0.14	-9999	-0.52	17	17
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.037	0.16	-9999	-0.52	49	49
GRB2/SOS1	-0.001	0.015	-9999	-0.34	1	1
HRAS/GTP	-0.07	0.13	-9999	-0.48	17	17
SHC1	0.009	0.05	-9999	-0.49	5	5
HRAS/GDP	-0.072	0.13	-9999	-0.49	17	17
FRAP1	-0.045	0.15	-9999	-0.5	17	17
EGF/EGFR dimer	-0.11	0.2	-9999	-0.43	132	132
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-0.49	1	1
ETA receptor/Endothelin-1	-0.059	0.14	-9999	-0.39	78	78

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.031	0.13	-9999	-0.3	77	77
FZD6	-0.016	0.12	-9999	-0.49	31	31
WNT6	-0.034	0.16	-9999	-0.53	45	45
WNT4	-0.032	0.15	-9999	-0.52	45	45
FZD3	0.011	0.046	-9999	-0.59	3	3
WNT5A	-0.013	0.12	-9999	-0.56	24	24
WNT11	-0.017	0.13	-9999	-0.54	29	29

×

TCGA08_p53

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
CDKN2A	-0.074	0.17	-10000	0	-0.42	104	104
TP53	-0.034	0.089	0.19	3	-0.43	14	17
Senescence	-0.034	0.089	0.19	3	-0.43	14	17
Apoptosis	-0.034	0.089	0.19	3	-0.43	14	17
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.049	0.1	0.27	76	-0.26	2	78
MDM4	0.005	0.066	-10000	0	-0.49	9	9

×

IL6-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.036	0.23	-10000	0	-0.68	17	17
CRP	-0.043	0.23	-10000	0	-0.66	20	20
cell cycle arrest	-0.056	0.25	-10000	0	-0.66	41	41
TIMP1	-0.08	0.27	-10000	0	-0.62	58	58
IL6ST	-0.03	0.16	-10000	0	-0.59	37	37
Rac1/GDP	-0.067	0.2	-10000	0	-0.44	74	74
AP1	-0.017	0.14	-10000	0	-0.48	13	13
GAB2	0.014	0.027	-10000	0	-0.59	1	1
TNFSF11	-0.044	0.23	-10000	0	-0.67	21	21
HSP90B1	0.005	0.16	-10000	0	-0.92	13	13
GAB1	0.013	0.035	-10000	0	-0.54	2	2
MAPK14	-0.097	0.23	-10000	0	-0.51	87	87
AKT1	0.058	0.03	-10000	0	-0.45	1	1
FOXO1	0.063	0.036	-10000	0	-0.42	1	1
MAP2K6	-0.085	0.2	-10000	0	-0.47	71	71
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.054	0.21	-10000	0	-0.48	62	62
MITF	-0.066	0.18	0.27	1	-0.42	75	76
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.014	0	-10000	0	-10000	0	0
A2M	0.018	0.072	-10000	0	-1.4	1	1
CEBPB	0.003	0.11	-10000	0	-0.57	17	17
GRB2/SOS1/GAB family/SHP2	0.004	0.078	-10000	0	-0.82	1	1
STAT3	-0.06	0.26	-10000	0	-0.69	42	42
STAT1	-0.008	0.035	-10000	0	-10000	0	0
CEBPD	-0.078	0.33	-10000	0	-0.93	47	47
PIK3CA	0.015	0.027	-10000	0	-0.59	1	1
PI3K	0.023	0.02	-10000	0	-0.43	1	1
JUN	0.003	0.075	-10000	0	-0.5	11	11
PIAS3/MITF	-0.055	0.18	-10000	0	-0.43	53	53
MAPK11	-0.1	0.23	-10000	0	-0.51	91	91
STAT3 (dimer)/FOXO1	0.015	0.21	-10000	0	-0.56	18	18
GRB2/SOS1/GAB family	-0.072	0.12	-10000	0	-0.45	31	31
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.064	0.17	-10000	0	-0.44	55	55
GRB2	0.014	0.022	-10000	0	-0.49	1	1
JAK2	0.014	0	-10000	0	-10000	0	0
LBP	-0.034	0.23	-10000	0	-0.63	29	29
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.012	0.009	-10000	0	-10000	0	0
MYC	-0.063	0.3	-10000	0	-0.94	34	34
FGG	-0.044	0.23	-10000	0	-0.67	21	21
macrophage differentiation	-0.056	0.25	-10000	0	-0.66	41	41
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.11	0.17	-10000	0	-0.41	81	81
JUNB	-0.057	0.27	-10000	0	-0.75	37	37
FOS	-0.094	0.22	-10000	0	-0.55	99	99
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.077	0.19	0.29	1	-0.42	83	84
STAT1/PIAS1	-0.054	0.18	0.29	1	-0.42	61	62
GRB2/SOS1/GAB family/SHP2/PI3K	0.045	0.032	-10000	0	-0.49	1	1
STAT3 (dimer)	-0.058	0.26	-10000	0	-0.69	41	41
PRKCD	-0.058	0.25	-10000	0	-0.58	60	60
IL6R	-0.015	0.12	-10000	0	-0.57	24	24
SOCS3	-0.15	0.34	-10000	0	-1	47	47
gp130 (dimer)/JAK1/JAK1/LMO4	-0.001	0.1	-10000	0	-0.35	37	37
Rac1/GTP	-0.069	0.2	-10000	0	-0.45	75	75
HCK	-0.008	0.11	-10000	0	-0.54	20	20
MAPKKK cascade	0.025	0.068	-10000	0	-0.91	1	1
bone resorption	-0.04	0.22	-10000	0	-0.63	22	22
IRF1	-0.044	0.24	-10000	0	-0.65	29	29
mol:GDP	-0.079	0.2	0.28	1	-0.44	87	88
SOS1	0.015	0.002	-10000	0	-10000	0	0
VAV1	-0.081	0.2	0.28	1	-0.44	87	88
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.1	0.22	-10000	0	-0.49	89	89
PTPN11	-0.002	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.1	0.2	-10000	0	-0.41	147	147
gp130 (dimer)/TYK2/TYK2/LMO4	-0.003	0.1	-10000	0	-0.35	37	37
gp130 (dimer)/JAK2/JAK2/LMO4	-0.003	0.1	-10000	0	-0.35	37	37
IL6	-0.13	0.24	-10000	0	-0.53	134	134
PIAS3	0.014	0	-10000	0	-10000	0	0
PTPRE	0.012	0.032	-10000	0	-0.6	1	1
PIAS1	0.009	0.053	-10000	0	-0.59	4	4
RAC1	0.015	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.067	0.16	0.26	1	-0.39	59	60
LMO4	0.014	0.012	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.12	0.2	0.35	1	-0.66	38	39
MCL1	0.064	0.027	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.059	0.12	-9999	-0.55	9	9
SMAD6-7/SMURF1	-0.004	0.036	-9999	-0.33	6	6
NOG	-0.063	0.2	-9999	-0.58	67	67
SMAD9	-0.028	0.16	-9999	-0.56	36	36
SMAD4	0.014	0	-9999	-10000	0	0
SMAD5	-0.001	0.12	-9999	-0.48	17	17
BMP7/USAG1	-0.092	0.16	-9999	-0.38	126	126
SMAD5/SKI	0.007	0.12	-9999	-0.46	16	16
SMAD1	0.044	0.029	-9999	-10000	0	0
BMP2	-0.078	0.22	-9999	-0.59	78	78
SMAD1/SMAD1/SMAD4	-0.003	0.025	-9999	-10000	0	0
BMPR1A	0.014	0	-9999	-10000	0	0
BMPR1B	-0.022	0.14	-9999	-0.59	31	31
BMPR1A-1B/BAMBI	-0.027	0.1	-9999	-0.39	35	35
AHSG	-0.076	0.21	-9999	-0.55	81	81
CER1	-0.014	0.099	-9999	-0.49	21	21
BMP2-4/CER1	-0.081	0.19	-9999	-0.45	93	93
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.014	0.16	-9999	-0.49	34	34
BMP2-4 (homodimer)	-0.082	0.2	-9999	-0.51	83	83
RGMB	0.004	0.074	-9999	-0.55	9	9
BMP6/BMPR2/BMPR1A-1B	-0.028	0.092	-9999	-0.33	36	36
RGMA	-0.002	0.097	-9999	-0.58	14	14
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.021	0.15	-9999	-0.46	36	36
BMP2-4/USAG1	-0.14	0.22	-9999	-0.42	171	171
SMAD6/SMURF1/SMAD5	0.007	0.12	-9999	-0.46	16	16
SOSTDC1	-0.11	0.23	-9999	-0.52	120	120
BMP7/BMPR2/BMPR1A-1B	-0.023	0.083	-9999	-0.32	38	38
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.004	0.097	-9999	-0.52	17	17
HFE2	0.003	0.062	-9999	-0.49	8	8
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.075	0.17	-9999	-0.43	89	89
SMAD5/SMAD5/SMAD4	0.007	0.12	-9999	-0.46	16	16
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.047	0.11	-9999	-0.4	34	34
BMP7 (homodimer)	0.006	0.07	-9999	-0.59	7	7
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.074	0.16	-9999	-0.41	93	93
SMAD1/SKI	0.05	0.028	-9999	-10000	0	0
SMAD6	0.007	0.062	-9999	-0.56	6	6
CTDSP2	0.01	0.044	-9999	-0.49	4	4
BMP2-4/FETUA	-0.12	0.21	-9999	-0.42	148	148
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.17	0.26	-9999	-0.55	166	166
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	-0.005	0.039	-9999	-0.28	10	10
BMPR1A-1B (homodimer)	-0.026	0.1	-9999	-0.43	31	31
CHRDL1	-0.078	0.21	-9999	-0.57	81	81
ENDOFIN/SMAD1	0.05	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.029	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	0.005	0.069	-9999	-0.51	9	9
SMURF2	0.011	0.046	-9999	-0.59	3	3
BMP2-4/CHRDL1	-0.12	0.2	-9999	-0.43	138	138
BMP2-4/GREM1	-0.17	0.22	-9999	-0.41	219	219
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.019	0.15	-9999	-0.52	36	36
SMAD1/SMAD6	0.05	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.006	0.07	-9999	-0.59	7	7
BMP6	-0.004	0.097	-9999	-0.53	17	17
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.014	0.14	-9999	-0.42	36	36
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.048	0.037	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0.027	-9999	-0.59	1	1
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.004	0.07	-9999	-0.49	10	10
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.052	0.18	-9999	-0.48	53	53
CHRD	0.006	0.07	-9999	-0.59	7	7
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.029	0.16	-9999	-0.51	36	36
BMP4	-0.014	0.13	-9999	-0.58	24	24
FST	-0.067	0.2	-9999	-0.54	75	75
BMP2-4/NOG	-0.11	0.24	-9999	-0.54	108	108
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.021	0.076	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.022	-9999	-0.49	1	1
LAT2	-0.052	0.18	-9999	-0.58	34	34
AP1	-0.11	0.18	-9999	-0.52	59	59
mol:PIP3	-0.064	0.2	-9999	-0.58	40	40
IKBKB	-0.03	0.11	-9999	-0.28	41	41
AKT1	-0.035	0.14	-9999	-0.46	15	15
IKBKG	-0.03	0.11	-9999	-0.28	37	37
MS4A2	-0.024	0.11	-9999	-0.49	26	26
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
MAP3K1	-0.019	0.16	-9999	-0.52	31	31
mol:Ca2+	-0.044	0.15	-9999	-0.41	40	40
LYN	0.003	0.074	-9999	-0.52	10	10
CBLB	-0.039	0.14	-9999	-0.46	29	29
SHC1	0.009	0.05	-9999	-0.49	5	5
RasGAP/p62DOK	-0.019	0.071	-9999	-0.32	14	14
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.008	0.06	-9999	-0.54	6	6
PLD2	-0.071	0.16	-9999	-0.36	73	73
PTPN13	-0.03	0.14	-9999	-0.56	20	20
PTPN11	0.01	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.004	0.12	-9999	-0.34	19	19
SYK	-0.014	0.13	-9999	-0.58	24	24
GRB2	0.013	0.022	-9999	-0.49	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.17	-9999	-0.59	39	39
LAT	-0.055	0.15	-9999	-0.42	48	48
PAK2	-0.028	0.17	-9999	-0.6	31	31
NFATC2	-0.099	0.19	-9999	-0.55	63	63
HRAS	-0.041	0.19	-9999	-0.64	34	34
GAB2	0.013	0.027	-9999	-0.59	1	1
PLA2G1B	0.04	0.022	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.19	-9999	-0.36	179	179
Antigen/IgE/Fc epsilon R1	-0.11	0.17	-9999	-0.33	179	179
mol:GDP	-0.05	0.2	-9999	-0.67	37	37
JUN	0.003	0.075	-9999	-0.5	11	11
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.001	-9999	-10000	0	0
FOS	-0.094	0.22	-9999	-0.55	99	99
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.065	0.14	-9999	-0.49	29	29
CHUK	-0.03	0.11	-9999	-0.28	37	37
KLRG1	-0.043	0.14	-9999	-0.5	24	24
VAV1	-0.054	0.18	-9999	-0.6	36	36
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.038	0.14	-9999	-0.52	22	22
negative regulation of mast cell degranulation	-0.035	0.14	-9999	-0.52	24	24
BTK	-0.073	0.2	-9999	-0.74	31	31
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.19	-9999	-0.38	114	114
GAB2/PI3K/SHP2	-0.082	0.13	-9999	-0.46	23	23
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.056	0.16	-9999	-0.42	45	45
RAF1	0.029	0.025	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.18	0.22	-9999	-0.44	157	157
FCER1G	-0.021	0.14	-9999	-0.57	30	30
FCER1A	-0.15	0.25	-9999	-0.54	148	148
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.16	-9999	-0.37	92	92
MAPK3	0.039	0.022	-9999	-10000	0	0
MAPK1	0.039	0.022	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.003	0.11	-9999	-0.6	13	13
DUSP1	-0.02	0.13	-9999	-0.53	32	32
NF-kappa-B/RelA	-0.033	0.049	-9999	-0.23	1	1
actin cytoskeleton reorganization	-0.035	0.13	-9999	-0.53	20	20
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.069	0.16	-9999	-0.63	30	30
FER	-0.051	0.15	-9999	-0.45	43	43
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.067	0.12	-9999	-0.36	51	51
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.048	0.21	-9999	-0.68	35	35
cytokine secretion	-0.024	0.036	-9999	-10000	0	0
SPHK1	-0.06	0.16	-9999	-0.48	42	42
PTK2	-0.037	0.14	-9999	-0.56	20	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.19	-9999	-0.65	36	36
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.052	0.19	-9999	-0.55	38	38
MAP2K2	0.035	0.022	-9999	-10000	0	0
MAP2K1	0.034	0.025	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.048	0.13	-9999	-0.48	23	23
MAP2K4	0.02	0.014	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.19	0.22	-9999	-0.46	161	161
mol:Choline	-0.07	0.16	-9999	-0.35	73	73
SHC/Grb2/SOS1	-0.059	0.11	-9999	-0.5	22	22
FYN	0.014	0	-9999	-10000	0	0
DOK1	0.012	0.035	-9999	-0.54	2	2
PXN	-0.027	0.13	-9999	-0.51	20	20
HCLS1	-0.055	0.17	-9999	-0.56	37	37
PRKCB	-0.053	0.14	-9999	-0.37	53	53
FCGR2B	-0.13	0.24	-9999	-0.53	138	138
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.036	0.14	-9999	-0.53	24	24
LCP2	-0.001	0.086	-9999	-0.5	15	15
PLA2G4A	-0.055	0.16	-9999	-0.45	47	47
RASA1	0.014	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.07	0.16	-9999	-0.35	73	73
IKK complex	-0.008	0.086	-9999	-0.22	21	21
WIPF1	0.014	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.002	0.17	-9999	-1.3	9	9
VDR	-0.064	0.19	-9999	-0.53	73	73
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.048	0.16	-9999	-0.45	31	31
RXRs/LXRs/DNA/Oxysterols	-0.075	0.22	-9999	-0.45	98	98
MED1	0.014	0	-9999	-10000	0	0
mol:9cRA	-0.009	0.024	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.027	0.056	-9999	-0.25	15	15
RXRs/NUR77	-0.035	0.14	-9999	-0.35	67	67
RXRs/PPAR	-0.017	0.12	-9999	-0.36	32	32
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.055	0.14	-9999	-0.39	73	73
RARs/VDR/DNA/Vit D3	-0.039	0.097	-9999	-0.31	34	34
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.064	0.19	-9999	-0.53	73	73
RARs/RARs/DNA/9cRA	0.017	0.032	-9999	-0.3	4	4
RARG	0.013	0.022	-9999	-0.49	1	1
RPS6KB1	0.02	0.067	-9999	-0.4	9	9
RARs/THRs/DNA/SMRT	0.027	0.056	-9999	-0.25	15	15
THRA	0.011	0.046	-9999	-0.59	3	3
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.055	0.14	-9999	-0.39	73	73
RXRs/PPAR/9cRA/PGJ2/DNA	-0.037	0.13	-9999	-0.35	63	63
NR1H4	-0.12	0.24	-9999	-0.53	131	131
RXRs/LXRs/DNA	-0.024	0.14	-9999	-0.42	26	26
NR1H2	0.011	0.017	-9999	-10000	0	0
NR1H3	0.009	0.02	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.058	0.16	-9999	-0.36	91	91
NR4A1	-0.019	0.13	-9999	-0.51	32	32
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.067	0.14	-9999	-0.31	90	90
RXRG	-0.066	0.2	-9999	-0.59	65	65
RXR alpha/CCPG	0.017	0.013	-9999	-10000	0	0
RXRA	0.011	0.017	-9999	-10000	0	0
RXRB	0.009	0.02	-9999	-10000	0	0
THRB	-0.012	0.12	-9999	-0.53	25	25
PPARG	-0.014	0.12	-9999	-0.56	25	25
PPARD	0.014	0	-9999	-10000	0	0
TNF	-0.19	0.41	-9999	-1	88	88
mol:Oxysterols	-0.007	0.022	-9999	-10000	0	0
cholesterol transport	-0.074	0.21	-9999	-0.44	98	98
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.011	0.046	-9999	-0.59	3	3
RXRs/NUR77/BCL2	-0.024	0.12	-9999	-0.31	68	68
SREBF1	-0.079	0.26	-9999	-0.91	29	29
RXRs/RXRs/DNA/9cRA	-0.036	0.13	-9999	-0.35	63	63
ABCA1	-0.079	0.26	-9999	-0.87	32	32
RARs/THRs	-0.016	0.062	-9999	-0.29	15	15
RXRs/FXR	-0.095	0.19	-9999	-0.38	122	122
BCL2	0.005	0.075	-9999	-0.59	8	8

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.087	0.28	-10000	0	-0.9	37	37
NCK1/PAK1/Dok-R	-0.096	0.13	-10000	0	-0.41	52	52
NCK1/Dok-R	-0.11	0.32	-10000	0	-1.1	38	38
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
mol:beta2-estradiol	0.015	0.064	0.22	30	-10000	0	30
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.009	0.05	-10000	0	-0.49	5	5
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.014	0.088	0.25	17	-0.48	7	24
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.11	0.26	-10000	0	-1	37	37
FN1	-0.004	0.093	-10000	0	-0.49	18	18
PLD2	-0.084	0.31	-10000	0	-1.1	37	37
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.18	0.26	-10000	0	-0.53	184	184
ELK1	-0.061	0.28	-10000	0	-0.99	37	37
GRB7	-0.031	0.14	-10000	0	-0.49	42	42
PAK1	-0.035	0.15	-10000	0	-0.5	49	49
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.29	-10000	0	-1	42	42
CDKN1A	-0.1	0.29	-10000	0	-0.71	65	65
ITGA5	-0.01	0.11	-10000	0	-0.5	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.11	0.32	-10000	0	-1.1	38	38
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	-0.059	0.22	-10000	0	-0.64	39	39
PLG	-0.092	0.31	-10000	0	-1.1	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.078	0.26	-10000	0	-0.86	37	37
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PIK3R1	0.014	0.002	-10000	0	-10000	0	0
ANGPT2	-0.11	0.29	-10000	0	-0.84	48	48
BMX	-0.11	0.32	-10000	0	-1.1	38	38
ANGPT1	-0.13	0.34	-10000	0	-1.2	42	42
tube development	-0.085	0.26	-10000	0	-0.67	58	58
ANGPT4	-0.05	0.18	-10000	0	-0.54	58	58
response to hypoxia	-0.008	0.021	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.18	0.36	-10000	0	-1.2	43	43
alpha5/beta1 Integrin	-0.018	0.079	-10000	0	-0.36	25	25
FGF2	0.011	0.044	-10000	0	-0.56	3	3
STAT5A (dimer)	-0.11	0.32	-10000	0	-0.8	57	57
mol:L-citrulline	-0.059	0.22	-10000	0	-0.64	39	39
AGTR1	-0.031	0.15	-10000	0	-0.55	41	41
MAPK14	-0.09	0.31	-10000	0	-1.1	36	36
Tie2/SHP2	-0.042	0.16	-10000	0	-1.2	8	8
TEK	-0.023	0.19	-10000	0	-1.3	8	8
RPS6KB1	-0.073	0.27	-10000	0	-0.86	36	36
Angiotensin II/AT1	-0.023	0.11	-10000	0	-0.4	41	41
Tie2/Ang1/GRB2	-0.087	0.32	-10000	0	-1.2	37	37
MAPK3	-0.068	0.29	-10000	0	-1	37	37
MAPK1	-0.068	0.29	-10000	0	-1	37	37
Tie2/Ang1/GRB7	-0.11	0.33	-10000	0	-1.2	37	37
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.091	0.32	-10000	0	-1.1	37	37
PI3K	-0.096	0.31	-10000	0	-1	36	36
FES	-0.09	0.31	-10000	0	-1.1	36	36
Crk/Dok-R	-0.11	0.32	-10000	0	-1.1	38	38
Tie2/Ang1/ABIN2	-0.087	0.32	-10000	0	-1.2	37	37
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.076	0.26	-10000	0	-0.79	37	37
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.073	0.27	-10000	0	-0.86	36	36
Tie2/Ang2	-0.13	0.34	-10000	0	-0.93	58	58
Tie2/Ang1	-0.099	0.34	-10000	0	-1.2	37	37
FOXO1	-0.084	0.28	-10000	0	-0.74	55	55
ELF1	0.019	0.032	-10000	0	-0.64	1	1
ELF2	-0.088	0.31	-10000	0	-1.1	37	37
mol:Choline	-0.078	0.3	-10000	0	-1.1	37	37
cell migration	-0.054	0.073	-10000	0	-0.23	46	46
FYN	-0.1	0.29	-10000	0	-0.77	58	58
DOK2	-0.071	0.2	-10000	0	-0.53	80	80
negative regulation of cell cycle	-0.091	0.26	-10000	0	-0.63	68	68
ETS1	-0.01	0.1	-10000	0	-0.58	10	10
PXN	-0.052	0.23	-10000	0	-0.7	36	36
ITGB1	0.012	0.031	-10000	0	-0.49	2	2
NOS3	-0.069	0.25	-10000	0	-0.74	39	39
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.17	0.27	-10000	0	-0.53	168	168
MAPKKK cascade	-0.078	0.3	-10000	0	-1.1	37	37
RASA1	0.014	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.092	0.33	-10000	0	-1.2	37	37
NCK1	0.013	0.027	-10000	0	-0.59	1	1
vasculogenesis	-0.05	0.2	-10000	0	-0.58	39	39
mol:Phosphatidic acid	-0.078	0.3	-10000	0	-1.1	37	37
mol:Angiotensin II	-0.001	0.008	-10000	0	-10000	0	0
mol:NADP	-0.059	0.22	-10000	0	-0.64	39	39
Rac1/GTP	-0.12	0.22	-10000	0	-0.79	37	37
MMP2	-0.097	0.32	-10000	0	-1.1	38	38

×

Coregulation of Androgen receptor activity

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
NRIP1	0.013	0.004	-9999	-10000	0	0
SVIL	-0.011	0.11	-9999	-0.5	24	24
ZNF318	0.019	0.018	-9999	-10000	0	0
JMJD2C	-0.003	0.021	-9999	-0.075	36	36
T-DHT/AR/Ubc9	-0.069	0.16	-9999	-0.36	109	109
CARM1	0.014	0.001	-9999	-10000	0	0
PRDX1	-0.014	0.13	-9999	-0.59	24	24
PELP1	0.015	0.003	-9999	-10000	0	0
CTNNB1	0.013	0.004	-9999	-10000	0	0
AKT1	0.015	0.005	-9999	-10000	0	0
PTK2B	-0.01	0.11	-9999	-0.49	24	24
MED1	0.015	0.005	-9999	-10000	0	0
MAK	-0.033	0.16	-9999	-0.5	51	51
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	-0.002	0.096	-9999	-0.59	13	13
GSN	0	0.089	-9999	-0.58	12	12
NCOA2	-0.027	0.15	-9999	-0.59	35	35
NCOA6	0.013	0.004	-9999	-10000	0	0
DNA-PK	0.008	0.025	-9999	-10000	0	0
NCOA4	0.014	0.001	-9999	-10000	0	0
PIAS3	0.013	0.004	-9999	-10000	0	0
cell proliferation	-0.041	0.11	-9999	-0.38	27	27
XRCC5	0.015	0.004	-9999	-10000	0	0
UBE3A	0.012	0.009	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.082	0.18	-9999	-0.38	122	122
FHL2	-0.047	0.21	-9999	-0.79	26	26
RANBP9	0.013	0.004	-9999	-10000	0	0
JMJD1A	-0.009	0.053	-9999	-0.11	98	98
CDK6	-0.032	0.15	-9999	-0.54	43	43
TGFB1I1	0.003	0.076	-9999	-0.53	10	10
T-DHT/AR/CyclinD1	-0.088	0.18	-9999	-0.38	127	127
XRCC6	0.015	0.004	-9999	-10000	0	0
T-DHT/AR	-0.077	0.18	-9999	-0.37	118	118
CTDSP1	0.013	0.004	-9999	-10000	0	0
CTDSP2	0.013	0.046	-9999	-0.49	4	4
BRCA1	0.009	0.044	-9999	-0.49	4	4
TCF4	0.015	0.028	-9999	-0.59	1	1
CDKN2A	-0.1	0.23	-9999	-0.56	104	104
SRF	0.017	0.027	-9999	-10000	0	0
NKX3-1	-0.06	0.18	-9999	-0.99	13	13
KLK3	-0.018	0.11	-9999	-10000	0	0
TMF1	0.012	0.027	-9999	-0.59	1	1
HNRNPA1	0.016	0.006	-9999	-10000	0	0
AOF2	-0.002	0.008	-9999	-10000	0	0
APPL1	0.027	0.01	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.077	0.17	-9999	-0.36	121	121
AR	-0.12	0.24	-9999	-0.57	109	109
UBA3	0.013	0.004	-9999	-10000	0	0
PATZ1	0.016	0.006	-9999	-10000	0	0
PAWR	-0.034	0.16	-9999	-0.53	45	45
PRKDC	0.015	0.004	-9999	-10000	0	0
PA2G4	0.016	0.007	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.062	0.15	-9999	-0.33	110	110
RPS6KA3	0.012	0.027	-9999	-0.59	1	1
T-DHT/AR/ARA70	-0.07	0.16	-9999	-0.36	109	109
LATS2	-0.001	0.094	-9999	-0.52	16	16
T-DHT/AR/PRX1	-0.076	0.17	-9999	-0.36	121	121
Cyclin D3/CDK11 p58	0	0.016	-9999	-0.35	1	1
VAV3	-0.12	0.23	-9999	-0.52	126	126
KLK2	-0.066	0.12	-9999	-0.44	36	36
CASP8	-0.001	0.089	-9999	-0.5	16	16
T-DHT/AR/TIF2/CARM1	-0.077	0.18	-9999	-0.36	131	131
TMPRSS2	-0.14	0.31	-9999	-0.69	100	100
CCND1	-0.017	0.13	-9999	-0.53	29	29
PIAS1	0.007	0.054	-9999	-0.59	4	4
mol:T-DHT	-0.011	0.031	-9999	-0.078	58	58
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.01	0.015	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.096	0.19	-9999	-0.38	139	139
CMTM2	-0.007	0.11	-9999	-0.56	19	19
SNURF	-0.008	0.11	-9999	-0.58	19	19
ZMIZ1	0.006	0.027	-9999	-10000	0	0
CCND3	0.013	0.022	-9999	-0.49	1	1
TGIF1	-0.007	0.11	-9999	-0.53	21	21
FKBP4	0.013	0.004	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.029	0.14	-9999	-0.38	57	57
CRKL	0.013	0.022	-9999	-0.49	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.009	0.053	-9999	-0.59	4	4
ITGA4	-0.051	0.18	-9999	-0.53	61	61
alpha4/beta7 Integrin/MAdCAM1	-0.12	0.17	-9999	-0.4	97	97
EPO	-0.007	0.098	-9999	-0.5	20	20
alpha4/beta7 Integrin	-0.076	0.17	-9999	-0.43	92	92
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.046	0.13	-9999	-0.39	61	61
EPO/EPOR (dimer)	-0.014	0.071	-9999	-0.36	20	20
lamellipodium assembly	0.009	0.022	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.001	0.019	-9999	-0.43	1	1
ARF6	0.014	0	-9999	-10000	0	0
JAK2	0	0.089	-9999	-0.3	10	10
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
MADCAM1	-0.11	0.23	-9999	-0.53	119	119
cell adhesion	-0.12	0.17	-9999	-0.4	97	97
CRKL/CBL	-0.001	0.015	-9999	-0.34	1	1
ITGB1	0.012	0.031	-9999	-0.49	2	2
SRC	-0.086	0.17	-9999	-0.35	122	122
ITGB7	-0.033	0.16	-9999	-0.54	44	44
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.12	0.18	-9999	-0.35	179	179
p130Cas/Crk/Dock1	-0.053	0.16	-9999	-0.5	17	17
VCAM1	-0.13	0.25	-9999	-0.56	132	132
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.034	0.093	-9999	-0.33	27	27
BCAR1	-0.072	0.17	-9999	-0.55	15	15
EPOR	0.013	0.022	-9999	-0.49	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0.009	0.022	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.018	0.006	-9999	-10000	0	0
RAS family/GTP	-0.07	0.15	-9999	-0.51	25	25
NFATC4	-0.061	0.13	-9999	-0.37	35	35
ERBB2IP	0.015	0.027	-9999	-0.59	1	1
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.089	0.15	-9999	-0.47	27	27
JUN	-0.02	0.1	-9999	-0.35	21	21
HRAS	0.014	0.001	-9999	-10000	0	0
DOCK7	-0.082	0.15	-9999	-0.46	30	30
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.12	0.18	-9999	-0.37	141	141
AKT1	0.01	0.004	-9999	-10000	0	0
BAD	0.02	0.003	-9999	-10000	0	0
MAPK10	-0.043	0.078	-9999	-0.24	28	28
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.094	0.17	-9999	-0.51	27	27
RAF1	-0.063	0.15	-9999	-0.49	25	25
ErbB2/ErbB3/neuregulin 2	-0.044	0.12	-9999	-0.33	68	68
STAT3	0.004	0.005	-9999	-10000	0	0
cell migration	-0.02	0.094	-9999	-0.24	24	24
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.15	0.27	-9999	-0.6	97	97
FOS	-0.12	0.22	-9999	-0.42	144	144
NRAS	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.089	0.15	-9999	-0.47	27	27
MAPK3	-0.12	0.22	-9999	-0.51	86	86
MAPK1	-0.12	0.22	-9999	-0.51	86	86
JAK2	-0.079	0.15	-9999	-0.44	27	27
NF2	-0.003	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.09	0.18	-9999	-0.33	141	141
NRG1	-0.17	0.27	-9999	-0.56	163	163
GRB2/SOS1	0.008	0.019	-9999	-0.34	1	1
MAPK8	-0.075	0.15	-9999	-0.33	71	71
MAPK9	-0.041	0.076	-9999	-0.23	26	26
ERBB2	-0.006	0.047	-9999	-0.38	8	8
ERBB3	-0.058	0.19	-9999	-0.57	62	62
SHC1	0.009	0.05	-9999	-0.49	5	5
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.001	0.011	-9999	-10000	0	0
STAT3 (dimer)	0.01	0.009	-9999	-10000	0	0
RNF41	0.023	0.009	-9999	-10000	0	0
FRAP1	0.009	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.071	0.097	-9999	-0.33	26	26
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.038	-9999	-0.31	8	8
CHRNA1	-0.14	0.26	-9999	-0.59	98	98
myelination	-0.053	0.13	-9999	-0.36	35	35
PPP3CB	-0.075	0.14	-9999	-0.4	29	29
KRAS	0.013	0.022	-9999	-0.49	1	1
RAC1-CDC42/GDP	-0.063	0.16	-9999	-0.51	26	26
NRG2	0.012	0.038	-9999	-0.59	2	2
mol:GDP	-0.09	0.17	-9999	-0.33	141	141
SOS1	0.014	0.001	-9999	-10000	0	0
MAP2K2	-0.06	0.15	-9999	-0.42	40	40
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.079	0.15	-9999	-0.44	27	27
MAP2K1	-0.13	0.22	-9999	-0.54	59	59
heart morphogenesis	-0.089	0.15	-9999	-0.47	27	27
RAS family/GDP	-0.067	0.15	-9999	-0.51	25	25
GRB2	0.013	0.022	-9999	-0.49	1	1
PRKACA	-0.007	0.009	-9999	-10000	0	0
CHRNE	0.002	0.044	-9999	-0.19	21	21
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.004	-9999	-10000	0	0
nervous system development	-0.089	0.15	-9999	-0.47	27	27
CDC42	0.014	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	-0.064	0.19	-10000	0	-0.53	73	73
Cbp/p300/PCAF	-0.003	0.034	-10000	0	-0.34	5	5
EP300	0.009	0.053	-10000	0	-0.59	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.015	0.063	-10000	0	-0.4	5	5
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.008	0.07	0.22	7	-0.34	3	10
RAR alpha/9cRA/Cyclin H	-0.052	0.084	-10000	0	-0.9	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.013	0.058	-10000	0	-0.33	5	5
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.064	0.11	-10000	0	-0.52	13	13
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.055	0.14	-10000	0	-0.39	73	73
RXRs/RARs/NRIP1/9cRA	-0.06	0.2	-10000	0	-0.6	26	26
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.064	0.19	-10000	0	-0.53	73	73
RARG	0.014	0.022	-10000	0	-0.49	1	1
RAR gamma1/9cRA	-0.001	0.013	-10000	0	-0.29	1	1
MAPK3	0.015	0	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0	0.095	-10000	0	-0.59	13	13
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.15	0.22	-10000	0	-0.56	92	92
RARA	-0.052	0.12	-10000	0	-0.25	101	101
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.004	0.097	-10000	0	-0.37	18	18
PRKCA	0.016	0.027	-10000	0	-0.59	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.073	0.2	-10000	0	-0.46	89	89
RXRG	-0.13	0.22	-10000	0	-0.44	123	123
RXRA	-0.036	0.11	-10000	0	-0.83	1	1
RXRB	-0.075	0.15	-10000	0	-0.34	89	89
VDR/Vit D3/DNA	-0.055	0.14	-10000	0	-0.39	73	73
RBP1	-0.074	0.2	-10000	0	-0.5	88	88
CRBP1/9-cic-RA	-0.062	0.14	-10000	0	-0.36	88	88
RARB	0.013	0.046	-10000	0	-0.59	3	3
PRKCG	-0.19	0.27	-10000	0	-0.54	190	190
MNAT1	0.013	0.022	-10000	0	-0.49	1	1
RAR alpha/RXRs	-0.063	0.21	-10000	0	-0.49	76	76
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.047	0.17	-10000	0	-0.39	76	76
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.095	-10000	0	-0.41	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.072	0.2	-10000	0	-0.46	89	89
positive regulation of DNA binding	-0.05	0.079	-10000	0	-0.81	1	1
NRIP1	-0.064	0.18	-10000	0	-0.58	26	26
RXRs/RARs	-0.08	0.2	-10000	0	-0.46	89	89
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-10000	0	-0.52	89	89
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	-0.001	0.012	-10000	0	-0.28	1	1
RAR alpha/9cRA	-0.037	0.063	-10000	0	-0.79	1	1
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.001	0.012	-10000	0	-10000	0	0

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.037	0.1	-10000	0	-0.32	61	61
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.12	0.19	-10000	0	-0.39	173	173
GNB1/GNG2	-0.003	0.032	-10000	0	-0.36	4	4
GNB1	0.014	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.039	0.11	-10000	0	-0.34	59	59
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	0.01	0.028	0.087	59	-10000	0	59
GNAL	-0.055	0.19	-10000	0	-0.59	59	59
GNG2	0.009	0.053	-10000	0	-0.59	4	4
CRH	-0.17	0.26	-10000	0	-0.54	173	173
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0.059	-10000	0	-0.36	13	13
MAPK11	0.003	0.049	-10000	0	-0.36	9	9

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0.022	-10000	0	-0.49	1	1
RAS family/GTP/Tiam1	0.029	0.038	-10000	0	-0.51	1	1
NT3 (dimer)/TRKC	-0.015	0.078	-10000	0	-0.39	20	20
NT3 (dimer)/TRKB	-0.073	0.15	-10000	0	-0.36	103	103
SHC/Grb2/SOS1/GAB1/PI3K	0.037	0.03	-10000	0	-0.45	1	1
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.079	0.2	-10000	0	-0.51	92	92
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
DYNLT1	0.012	0.038	-10000	0	-0.59	2	2
NTRK1	-0.01	0.11	-10000	0	-0.52	23	23
NTRK2	-0.018	0.14	-10000	0	-0.59	27	27
NTRK3	0.009	0.053	-10000	0	-0.59	4	4
NT-4/5 (dimer)/TRKB	-0.072	0.16	-10000	0	-0.37	101	101
neuron apoptosis	0.13	0.16	0.47	62	-10000	0	62
SHC 2-3/Grb2	-0.12	0.2	-10000	0	-0.51	62	62
SHC1	0.009	0.05	-10000	0	-0.49	5	5
SHC2	-0.07	0.11	-10000	0	-0.4	28	28
SHC3	-0.16	0.23	-10000	0	-0.54	112	112
STAT3 (dimer)	0.007	0.069	-10000	0	-0.34	12	12
NT3 (dimer)/TRKA	-0.068	0.14	-10000	0	-0.34	102	102
RIN/GDP	-0.038	0.11	-10000	0	-0.25	22	22
GIPC1	0.013	0.022	-10000	0	-0.49	1	1
KRAS	0.013	0.022	-10000	0	-0.49	1	1
DNAJA3	-0.069	0.12	-10000	0	-0.38	45	45
RIN/GTP	-0.16	0.2	-10000	0	-0.4	204	204
CCND1	-0.001	0.15	-10000	0	-0.58	29	29
MAGED1	0.014	0	-10000	0	-10000	0	0
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.01	0.088	-10000	0	-0.5	16	16
SHC/GRB2/SOS1	-0.003	0.03	-10000	0	-0.28	6	6
GRB2	0.013	0.022	-10000	0	-0.49	1	1
NGF (dimer)/TRKA/MATK	-0.12	0.2	-10000	0	-0.38	168	168
TRKA/NEDD4-2	-0.026	0.097	-10000	0	-0.38	35	35
ELMO1	0.001	0.088	-10000	0	-0.59	11	11
RhoG/GTP/ELMO1/DOCK1	-0.011	0.062	-10000	0	-0.36	15	15
NGF	-0.074	0.21	-10000	0	-0.55	79	79
HRAS	0.014	0	-10000	0	-10000	0	0
DOCK1	0.009	0.053	-10000	0	-0.59	4	4
GAB2	0.013	0.027	-10000	0	-0.59	1	1
RIT2	-0.21	0.28	-10000	0	-0.55	204	204
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.012	0.035	-10000	0	-0.54	2	2
DNM1	-0.1	0.22	-10000	0	-0.52	109	109
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.073	0.13	-10000	0	-0.37	56	56
mol:GDP	0.045	0.066	-10000	0	-0.46	2	2
NGF (dimer)	-0.074	0.21	-10000	0	-0.55	79	79
RhoG/GDP	-0.009	0.063	-10000	0	-0.44	11	11
RIT1/GDP	0.04	0.048	-10000	0	-0.29	2	2
TIAM1	0.013	0.027	-10000	0	-0.59	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.075	0.14	-10000	0	-0.32	120	120
KIDINS220/CRKL/C3G	-0.001	0.015	-10000	0	-0.34	1	1
SHC/RasGAP	-0.003	0.034	-10000	0	-0.34	5	5
FRS2 family/SHP2	-0.001	0.02	-10000	0	-0.32	2	2
SHC/GRB2/SOS1/GAB1	-0.004	0.036	-10000	0	-0.57	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.008	0.092	-10000	0	-0.49	18	18
RAP1/GDP	-0.005	0.023	-10000	0	-0.24	2	2
KIDINS220/CRKL	0.013	0.022	-10000	0	-0.49	1	1
BDNF (dimer)	-0.079	0.2	-10000	0	-0.51	92	92
ubiquitin-dependent protein catabolic process	-0.071	0.15	-10000	0	-0.35	106	106
Schwann cell development	-0.02	0.027	-10000	0	-10000	0	0
EHD4	0.007	0.059	-10000	0	-0.49	7	7
FRS2 family/GRB2/SOS1	-0.002	0.021	-10000	0	-0.32	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.043	0.018	-10000	0	-10000	0	0
RAP1B	0.013	0.022	-10000	0	-0.49	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.061	0.12	-10000	0	-0.48	18	18
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
Rap1/GTP	-0.022	0.044	-10000	0	-10000	0	0
STAT3	0.007	0.068	-10000	0	-0.34	12	12
axon guidance	-0.059	0.11	-10000	0	-0.46	18	18
MAPK3	-0.087	0.19	-10000	0	-0.39	109	109
MAPK1	-0.087	0.19	-10000	0	-0.39	109	109
CDC42/GDP	0.04	0.048	-10000	0	-0.29	2	2
NTF3	-0.008	0.092	-10000	0	-0.49	18	18
NTF4	-0.01	0.088	-10000	0	-0.5	16	16
NGF (dimer)/TRKA/FAIM	-0.067	0.14	-10000	0	-0.34	101	101
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.009	0.053	-10000	0	-0.59	4	4
GAB1	0.012	0.035	-10000	0	-0.54	2	2
RASGRF1	-0.12	0.17	-10000	0	-0.39	107	107
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	0.013	0.072	-10000	0	-0.32	21	21
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.014	0.074	-10000	0	-10000	0	0
Rac1/GDP	0.04	0.048	-10000	0	-0.29	2	2
NGF (dimer)/TRKA/GRIT	-0.066	0.14	-10000	0	-0.34	98	98
neuron projection morphogenesis	-0.037	0.13	-10000	0	-0.49	13	13
NGF (dimer)/TRKA/NEDD4-2	-0.072	0.15	-10000	0	-0.35	106	106
MAP2K1	0.038	0.04	-10000	0	-0.53	1	1
NGFR	-0.063	0.19	-10000	0	-0.54	72	72
NGF (dimer)/TRKA/GIPC/GAIP	-0.05	0.14	-10000	0	-0.43	24	24
RAS family/GTP/PI3K	0.033	0.015	-10000	0	-0.26	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.019	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
PRKCI	0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
MAPKKK cascade	-0.086	0.2	-10000	0	-0.6	63	63
RASA1	0.014	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.016	0.077	-10000	0	-0.37	23	23
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.064	0.12	-10000	0	-0.35	43	43
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.066	0.13	-10000	0	-0.33	71	71
MATK	-0.093	0.22	-10000	0	-0.55	97	97
NEDD4L	0	0.086	-10000	0	-0.53	13	13
RAS family/GDP	-0.004	0.021	-10000	0	-0.26	1	1
NGF (dimer)/TRKA	-0.075	0.13	-10000	0	-0.33	91	91
Rac1/GTP	-0.065	0.096	-10000	0	-0.31	40	40
FRS2 family/SHP2/CRK family	-0.001	0.019	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0	0.093	-9999	-0.32	40	40
EPHB2	0	0.087	-9999	-0.52	14	14
Syndecan-2/TACI	-0.011	0.086	-9999	-0.33	33	33
LAMA1	-0.065	0.2	-9999	-0.57	70	70
Syndecan-2/alpha2 ITGB1	-0.028	0.15	-9999	-0.54	19	19
HRAS	0.014	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.015	0.071	-9999	-0.34	23	23
ITGA5	-0.01	0.11	-9999	-0.5	24	24
BAX	0.02	0.085	-9999	-10000	0	0
EPB41	0.011	0.044	-9999	-0.56	3	3
positive regulation of cell-cell adhesion	-0.013	0.062	-9999	-0.3	23	23
LAMA3	-0.041	0.17	-9999	-0.54	51	51
EZR	0.004	0.08	-9999	-0.59	9	9
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.016	0.12	-9999	-0.5	30	30
Syndecan-2/MMP2	-0.006	0.1	-9999	-0.33	47	47
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.034	0.11	-9999	-0.38	46	46
dendrite morphogenesis	0.002	0.096	-9999	-0.35	34	34
Syndecan-2/GM-CSF	-0.014	0.071	-9999	-0.34	23	23
determination of left/right symmetry	0.003	0.088	-9999	-0.4	23	23
Syndecan-2/PKC delta	-0.009	0.12	-9999	-0.4	43	43
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	0.012	0.068	-9999	-0.32	16	16
MAPK1	0.012	0.068	-9999	-0.32	16	16
Syndecan-2/RACK1	-0.012	0.058	-9999	-0.3	16	16
NF1	0.012	0.038	-9999	-0.59	2	2
FGFR/FGF/Syndecan-2	0.003	0.088	-9999	-0.4	23	23
ITGA2	-0.033	0.16	-9999	-0.54	44	44
MAPK8	0.011	0.095	-9999	-0.35	29	29
Syndecan-2/alpha2/beta1 Integrin	-0.041	0.17	-9999	-0.38	79	79
Syndecan-2/Kininogen	-0.021	0.093	-9999	-0.31	47	47
ITGB1	0.012	0.031	-9999	-0.49	2	2
SRC	0.027	0.061	-9999	-0.27	16	16
Syndecan-2/CASK/Protein 4.1	-0.015	0.072	-9999	-0.33	24	24
extracellular matrix organization	0.004	0.093	-9999	-0.36	30	30
actin cytoskeleton reorganization	0	0.093	-9999	-0.32	40	40
Syndecan-2/Caveolin-2/Ras	0.003	0.096	-9999	-0.33	20	20
Syndecan-2/Laminin alpha3	-0.023	0.13	-9999	-0.35	69	69
Syndecan-2/RasGAP	-0.011	0.053	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.018	0.079	-9999	-0.36	25	25
PRKCD	-0.018	0.14	-9999	-0.59	27	27
Syndecan-2 dimer	0.002	0.096	-9999	-0.35	34	34
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.034	0.06	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.005	0.072	-9999	-0.49	11	11
RASA1	0.014	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.034	0.11	-9999	-0.38	46	46
Syndecan-2/Synbindin	0.011	0.075	-9999	-0.33	23	23
TGFB1	0.004	0.08	-9999	-0.59	9	9
CASP3	0.002	0.12	-9999	-0.38	36	36
FN1	-0.004	0.093	-9999	-0.49	18	18
Syndecan-2/IL8	-0.096	0.18	-9999	-0.33	176	176
SDC2	0.003	0.088	-9999	-0.4	23	23
KNG1	-0.019	0.1	-9999	-0.49	24	24
Syndecan-2/Neurofibromin	0.009	0.08	-9999	-0.35	24	24
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	0.001	0.003	-9999	-10000	0	0
Syndecan-2/TGFB1	0.004	0.094	-9999	-0.36	30	30
Syndecan-2/Syntenin/PI-4-5-P2	-0.013	0.063	-9999	-0.3	23	23
Syndecan-2/Ezrin	0.014	0.093	-9999	-0.4	20	20
PRKACA	0.019	0.073	-9999	-0.33	18	18
angiogenesis	-0.096	0.18	-9999	-0.33	176	176
MMP2	-0.013	0.12	-9999	-0.54	25	25
IL8	-0.16	0.26	-9999	-0.53	162	162
calcineurin-NFAT signaling pathway	-0.011	0.085	-9999	-0.33	33	33

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.009	0.057	0.22	24	-10000	0	24
RFC1	0.009	0.057	0.22	22	-10000	0	22
PRKDC	0.009	0.057	0.22	22	-10000	0	22
RIPK1	0.016	0.003	-10000	0	-10000	0	0
CASP7	-0.004	0.072	0.25	16	-0.31	6	22
FASLG/FAS/FADD/FAF1	-0.009	0.086	0.22	20	-0.31	15	35
MAP2K4	-0.003	0.12	-10000	0	-0.38	11	11
mol:ceramide	-0.003	0.096	-10000	0	-0.39	11	11
GSN	0	0.072	0.25	6	-0.34	10	16
FASLG/FAS/FADD/FAF1/Caspase 8	-0.001	0.091	-10000	0	-0.35	12	12
FAS	-0.008	0.1	-10000	0	-0.55	18	18
BID	0.006	0.079	0.3	17	-0.3	13	30
MAP3K1	0.01	0.091	0.22	15	-0.3	7	22
MAP3K7	0.013	0.004	-10000	0	-10000	0	0
RB1	0.008	0.06	0.22	22	-0.36	1	23
CFLAR	0.015	0.022	-10000	0	-0.47	1	1
HGF/MET	-0.15	0.2	-10000	0	-0.37	207	207
ARHGDIB	0.006	0.064	0.22	22	-0.36	3	25
FADD	0.011	0.007	-10000	0	-10000	0	0
actin filament polymerization	0	0.072	0.34	10	-0.25	6	16
NFKB1	-0.039	0.066	-10000	0	-10000	0	0
MAPK8	-0.026	0.17	-10000	0	-0.43	48	48
DFFA	0.009	0.057	0.22	24	-10000	0	24
DNA fragmentation during apoptosis	0.009	0.057	0.22	22	-10000	0	22
FAS/FADD/MET	-0.1	0.16	-10000	0	-0.37	106	106
CFLAR/RIP1	0.014	0.017	-10000	0	-0.32	1	1
FAIM3	-0.027	0.15	-10000	0	-0.54	39	39
FAF1	0.011	0.027	-10000	0	-0.59	1	1
PARP1	0.008	0.059	0.22	22	-0.28	1	23
DFFB	0.009	0.057	0.22	22	-10000	0	22
CHUK	-0.032	0.057	-10000	0	-10000	0	0
FASLG	-0.028	0.13	-10000	0	-0.5	34	34
FAS/FADD	0.002	0.077	-10000	0	-0.4	18	18
HGF	-0.079	0.2	-10000	0	-0.51	91	91
LMNA	0.006	0.061	0.25	8	-0.35	3	11
CASP6	0.007	0.064	0.27	8	-0.38	3	11
CASP10	0.01	0.024	-10000	0	-0.5	1	1
CASP3	0.01	0.068	0.26	24	-10000	0	24
PTPN13	0.006	0.069	-10000	0	-0.58	7	7
CASP8	0.01	0.1	0.31	34	-0.34	16	50
IL6	-0.14	0.37	-10000	0	-1.2	46	46
MET	-0.15	0.25	-10000	0	-0.53	150	150
ICAD/CAD	0.009	0.053	0.25	8	-10000	0	8
FASLG/FAS/FADD/FAF1/Caspase 10	-0.003	0.097	-10000	0	-0.39	11	11
activation of caspase activity by cytochrome c	0.006	0.079	0.3	17	-0.3	13	30
PAK2	0.008	0.057	0.22	22	-10000	0	22
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.008	0.066	-9999	-0.31	21	21
ADCY5	0	0.091	-9999	-0.37	28	28
ADCY6	0.014	0.048	-9999	-0.31	11	11
ADCY7	0.014	0.048	-9999	-0.31	11	11
ADCY1	-0.052	0.15	-9999	-0.35	101	101
ADCY2	0.004	0.081	-9999	-0.35	24	24
ADCY3	0.014	0.048	-9999	-0.31	11	11
ADCY8	-0.03	0.13	-9999	-0.35	70	70
PRKCE	0.004	0.057	-9999	-0.38	11	11
ADCY9	0.012	0.06	-9999	-0.34	14	14
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.008	0.098	-9999	-0.35	22	22

×

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	0.009	0.056	-10000	0	-0.59	4	4
HSPA8	0.013	0.027	-10000	0	-0.59	1	1
SMAD3/SMAD4/ER alpha	-0.025	0.11	0.22	3	-0.39	25	28
AKT1	0.008	0.023	-10000	0	-10000	0	0
GSC	-0.16	0.48	-10000	0	-1.4	66	66
NKX2-5	-0.093	0.2	-10000	0	-0.5	102	102
muscle cell differentiation	0.15	0.19	0.49	88	-10000	0	88
SMAD2-3/SMAD4/SP1	-0.007	0.11	-10000	0	-0.46	6	6
SMAD4	-0.016	0.065	-10000	0	-0.4	1	1
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.014	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.022	0.11	-10000	0	-0.32	52	52
SMAD3/SMAD4/VDR	-0.034	0.12	-10000	0	-0.39	15	15
MYC	-0.008	0.12	-10000	0	-0.55	25	25
CDKN2B	-0.12	0.45	-10000	0	-1.4	55	55
AP1	-0.029	0.16	-10000	0	-0.53	24	24
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.043	0.063	-10000	0	-0.54	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.011	0.13	-10000	0	-0.38	33	33
SP3	0.016	0.008	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.016	0.1	-10000	0	-0.56	16	16
SMAD3/SMAD4/GR	-0.01	0.062	-10000	0	-0.42	1	1
GATA3	-0.13	0.24	-10000	0	-0.56	115	115
SKI/SIN3/HDAC complex/NCoR1	0.045	0.036	-10000	0	-0.36	1	1
MEF2C/TIF2	-0.077	0.18	-10000	0	-0.51	44	44
endothelial cell migration	0.22	0.48	1.4	71	-10000	0	71
MAX	0.023	0.019	-10000	0	-10000	0	0
RBBP7	0.014	0.002	-10000	0	-10000	0	0
RBBP4	0.013	0.027	-10000	0	-0.59	1	1
RUNX2	-0.006	0.1	-10000	0	-0.53	19	19
RUNX3	-0.03	0.15	-10000	0	-0.55	40	40
RUNX1	-0.053	0.18	-10000	0	-0.53	64	64
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.023	0.019	-10000	0	-10000	0	0
VDR	-0.064	0.19	-10000	0	-0.53	73	73
CDKN1A	-0.048	0.29	-10000	0	-1.3	22	22
KAT2B	0.013	0.023	-10000	0	-0.49	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.027	0.12	-10000	0	-0.39	21	21
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.014	0.002	-10000	0	-10000	0	0
SERPINE1	-0.22	0.49	-10000	0	-1.4	71	71
SMAD3/SMAD4/ATF2	-0.027	0.08	-10000	0	-0.38	15	15
SMAD3/SMAD4/ATF3	-0.05	0.12	-10000	0	-0.39	45	45
SAP30	0.013	0.027	-10000	0	-0.59	1	1
Cbp/p300/PIAS3	0.014	0.056	-10000	0	-0.35	4	4
JUN	-0.023	0.16	-10000	0	-0.53	24	24
SMAD3/SMAD4/IRF7	-0.033	0.097	-10000	0	-0.41	20	20
TFE3	0.008	0.029	-10000	0	-10000	0	0
COL1A2	-0.046	0.16	-10000	0	-0.46	60	60
mesenchymal cell differentiation	0.03	0.091	0.4	19	-10000	0	19
DLX1	-0.16	0.26	-10000	0	-0.54	160	160
TCF3	0.012	0.038	-10000	0	-0.59	2	2
FOS	-0.091	0.22	-10000	0	-0.55	99	99
SMAD3/SMAD4/Max	-0.01	0.062	-10000	0	-0.36	2	2
Cbp/p300/SNIP1	0.007	0.039	-10000	0	-0.35	4	4
ZBTB17	0.019	0.018	-10000	0	-10000	0	0
LAMC1	0.001	0.11	-10000	0	-0.5	17	17
TGIF2/HDAC complex/SMAD3/SMAD4	-0.022	0.073	-10000	0	-0.43	8	8
IRF7	-0.01	0.11	-10000	0	-0.52	23	23
ESR1	-0.013	0.12	-10000	0	-0.54	26	26
HNF4A	-0.033	0.14	-10000	0	-0.49	41	41
MEF2C	-0.064	0.18	-10000	0	-0.52	33	33
SMAD2-3/SMAD4	-0.035	0.073	-10000	0	-0.37	6	6
Cbp/p300/Src-1	0.01	0.045	-10000	0	-0.35	4	4
IGHV3OR16-13	-0.015	0.032	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.007	0.063	-10000	0	-0.57	6	6
CREBBP	0.014	0.012	-10000	0	-10000	0	0
SKIL	0.006	0.07	-10000	0	-0.59	7	7
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC2	0.014	0.002	-10000	0	-10000	0	0
SNIP1	0.014	0.005	-10000	0	-10000	0	0
GCN5L2	-0.001	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.008	0.083	-10000	0	-0.4	5	5
MSG1/HSC70	-0.021	0.12	-10000	0	-0.37	53	53
SMAD2	-0.004	0.047	-10000	0	-10000	0	0
SMAD3	-0.005	0.056	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.009	0.074	-10000	0	-0.34	6	6
SMAD2/SMAD2/SMAD4	-0.003	0.032	-10000	0	-10000	0	0
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
NCOA2	-0.027	0.15	-10000	0	-0.59	35	35
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.14	0.19	-10000	0	-0.39	179	179
SMAD2-3/SMAD4/SP1/MIZ-1	0.004	0.11	-10000	0	-0.44	7	7
IFNB1	-0.007	0.1	-10000	0	-0.48	10	10
SMAD3/SMAD4/MEF2C	-0.068	0.18	-10000	0	-0.53	31	31
CITED1	-0.041	0.16	-10000	0	-0.53	52	52
SMAD2-3/SMAD4/ARC105	-0.011	0.073	-10000	0	-0.37	3	3
RBL1	-0.009	0.11	-10000	0	-0.57	20	20
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.027	0.19	-10000	0	-0.53	56	56
RUNX1-3/PEBPB2	-0.064	0.14	-10000	0	-0.35	94	94
SMAD7	-0.011	0.14	-10000	0	-0.56	8	8
MYC/MIZ-1	-0.001	0.099	-10000	0	-0.38	25	25
SMAD3/SMAD4	-0.042	0.19	0.3	37	-0.42	61	98
IL10	-0.14	0.28	-10000	0	-0.61	109	109
PIASy/HDAC complex	0.016	0.013	-10000	0	-10000	0	0
PIAS3	0.013	0.007	-10000	0	-10000	0	0
CDK2	0	0.086	-10000	0	-0.53	13	13
IL5	-0.085	0.19	-10000	0	-0.52	40	40
CDK4	-0.001	0.089	-10000	0	-0.49	16	16
PIAS4	0.016	0.013	-10000	0	-10000	0	0
ATF3	-0.037	0.16	-10000	0	-0.51	50	50
SMAD3/SMAD4/SP1	-0.009	0.1	-10000	0	-0.42	7	7
FOXG1	-0.024	0.15	-10000	0	-0.58	33	33
FOXO3	0.017	0.032	-10000	0	-10000	0	0
FOXO1	0.014	0.045	-10000	0	-0.42	3	3
FOXO4	0.016	0.039	-10000	0	-0.51	1	1
heart looping	-0.063	0.18	-10000	0	-0.52	33	33
CEBPB	-0.008	0.11	-10000	0	-0.57	17	17
SMAD3/SMAD4/DLX1	-0.12	0.17	-10000	0	-0.38	133	133
MYOD1	-0.18	0.27	-10000	0	-0.55	177	177
SMAD3/SMAD4/HNF4	-0.045	0.1	-10000	0	-0.35	30	30
SMAD3/SMAD4/GATA3	-0.13	0.19	-10000	0	-0.48	74	74
SnoN/SIN3/HDAC complex/NCoR1	0.006	0.07	-10000	0	-0.59	7	7
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.061	0.14	-10000	0	-0.43	40	40
SMAD3/SMAD4/SP1-3	0.008	0.098	-10000	0	-0.44	5	5
MED15	0.014	0	-10000	0	-10000	0	0
SP1	0.004	0.041	-10000	0	-10000	0	0
SIN3B	0.014	0.002	-10000	0	-10000	0	0
SIN3A	0.014	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.073	0.16	-10000	0	-0.44	37	37
ITGB5	0.019	0.11	-10000	0	-0.66	6	6
TGIF/SIN3/HDAC complex/CtBP	0.043	0.044	-10000	0	-0.44	1	1
SMAD3/SMAD4/AR	-0.093	0.16	-10000	0	-0.38	95	95
AR	-0.11	0.23	-10000	0	-0.56	109	109
negative regulation of cell growth	-0.007	0.12	-10000	0	-0.43	20	20
SMAD3/SMAD4/MYOD	-0.14	0.18	-10000	0	-0.39	134	134
E2F5	0.011	0.046	-10000	0	-0.59	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.007	0.097	-10000	0	-0.35	9	9
SMAD2-3/SMAD4/FOXO1-3a-4	-0.01	0.13	-10000	0	-0.37	41	41
TFDP1	0.013	0.027	-10000	0	-0.59	1	1
SMAD3/SMAD4/AP1	-0.029	0.16	-10000	0	-0.54	24	24
SMAD3/SMAD4/RUNX2	-0.03	0.092	-10000	0	-0.41	19	19
TGIF2	0.007	0.063	-10000	0	-0.57	6	6
TGIF1	-0.008	0.11	-10000	0	-0.53	21	21
ATF2	-0.001	0.095	-10000	0	-0.59	13	13

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	-0.007	0.11	-9999	-0.56	19	19
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.089	0.15	-9999	-0.32	140	140
CaM/Ca2+	-0.002	0.025	-9999	-0.4	2	2
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.052	0.15	-9999	-0.32	79	79
IQGAP1/CaM	-0.009	0.057	-9999	-0.38	12	12
DAB1	-0.089	0.22	-9999	-0.56	92	92
IQGAP1	0.004	0.076	-9999	-0.53	10	10
PLA2G7	-0.04	0.17	-9999	-0.55	49	49
CALM1	0.012	0.035	-9999	-0.54	2	2
DYNLT1	0.012	0.038	-9999	-0.59	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.002	0.027	-9999	-0.43	2	2
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.014	0	-9999	-10000	0	0
CDK5R1	-0.021	0.14	-9999	-0.59	30	30
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	-0.1	0.23	-9999	-0.57	103	103
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.21	-9999	-0.39	210	210
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.069	0.19	-9999	-0.54	43	43
MAP1B	-0.001	0.016	-9999	-0.31	1	1
RAC1	-0.003	0.019	-9999	-10000	0	0
p35/CDK5	-0.047	0.16	-9999	-0.57	16	16
RELN	-0.14	0.25	-9999	-0.55	139	139
PAFAH/LIS1	-0.005	0.11	-9999	-0.36	31	31
LIS1/CLIP170	0.029	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.08	0.13	-9999	-0.43	39	39
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.085	0.2	-9999	-0.52	49	49
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.082	0.2	-9999	-0.54	53	53
LIS1/IQGAP1	0.022	0.047	-9999	-0.36	4	4
RHOA	-0.003	0.019	-9999	-10000	0	0
PAFAH1B1	0.025	0	-9999	-10000	0	0
PAFAH1B3	0.014	0	-9999	-10000	0	0
PAFAH1B2	-0.005	0.1	-9999	-0.59	16	16
MAP1B/LIS1/Dynein heavy chain	0.027	0.011	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.1	0.16	-9999	-0.52	43	43
LRP8	0.012	0.038	-9999	-0.59	2	2
NDEL1/Katanin 60	-0.069	0.19	-9999	-0.54	43	43
P39/CDK5	-0.089	0.19	-9999	-0.53	40	40
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.029	0	-9999	-10000	0	0
CDK5	-0.039	0.14	-9999	-0.29	79	79
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.1	0.2	-9999	-0.56	39	39
RELN/VLDLR	-0.09	0.14	-9999	-0.34	93	93
CDC42	-0.003	0.019	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.044	0.15	-10000	0	-0.72	19	19
HDAC1	0.008	0.054	-10000	0	-0.59	4	4
AES	0.014	0.004	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	0.004	0.078	-10000	0	-0.58	9	9
LRP6/FZD1	-0.005	0.04	-10000	0	-0.34	7	7
TLE1	0.012	0.038	-10000	0	-0.59	2	2
AP1	-0.028	0.12	-10000	0	-0.3	69	69
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0	0.092	-10000	0	-0.59	12	12
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.027	0.072	-10000	0	-10000	0	0
NICD/RBPSUH	-0.02	0.11	-10000	0	-0.59	19	19
WIF1	-0.28	0.28	-10000	0	-0.54	269	269
NOTCH1	-0.023	0.12	-10000	0	-0.63	19	19
PSENEN	0.014	0	-10000	0	-10000	0	0
KREMEN2	-0.052	0.18	-10000	0	-0.53	63	63
DKK1	-0.12	0.24	-10000	0	-0.53	124	124
beta catenin/beta TrCP1	0.017	0.046	0.33	3	-10000	0	3
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	-0.001	0.045	0.23	4	-0.21	18	22
CtBP/CBP/TCF1/TLE1/AES	0.03	0.051	0.28	4	-0.26	6	10
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.094	0.22	-10000	0	-0.55	99	99
JUN	0.003	0.075	-10000	0	-0.5	11	11
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
CTNNB1	0.009	0.049	0.32	4	-10000	0	4
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	163	163
HNF1A	0.013	0.027	-10000	0	-0.59	1	1
CTBP1	0.014	0.004	-10000	0	-10000	0	0
MYC	-0.038	0.29	-10000	0	-1.4	21	21
NKD1	-0.004	0.099	-10000	0	-0.54	17	17
FZD1	0.008	0.054	-10000	0	-0.49	6	6
NOTCH1 precursor/Deltex homolog 1	-0.025	0.12	-10000	0	-0.6	19	19
apoptosis	-0.028	0.12	-10000	0	-0.29	69	69
Delta 1/NOTCHprecursor	-0.043	0.15	-10000	0	-0.71	19	19
DLL1	-0.033	0.16	-10000	0	-0.59	40	40
PPARD	0.02	0.027	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.002	0.061	0.23	4	-0.49	3	7
DVL1	-0.021	0.025	-10000	0	-10000	0	0
CSNK2A1	0.014	0.003	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.35	168	168
LRP6	0.013	0.022	-10000	0	-0.49	1	1
CSNK1A1	0.014	0.003	-10000	0	-10000	0	0
NLK	0.016	0.015	-10000	0	-10000	0	0
CCND1	-0.023	0.23	-10000	0	-1.4	12	12
WNT1	-0.028	0.13	-10000	0	-0.49	40	40
Axin1/APC/beta catenin	0.017	0.062	0.31	4	-0.41	2	6
DKK2	-0.11	0.23	-10000	0	-0.54	117	117
NOTCH1 precursor/DVL1	-0.022	0.11	-10000	0	-0.56	19	19
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
FRAT1	0.01	0.049	-10000	0	-0.54	4	4
NOTCH/Deltex homolog 1	-0.027	0.12	-10000	0	-0.61	19	19
PPP2R5D	-0.003	0.05	0.25	17	-10000	0	17
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.16	0.18	-10000	0	-0.37	144	144
RBPJ	0.013	0.022	-10000	0	-0.49	1	1
CREBBP	0.017	0.005	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.014	0.027	-9999	-0.59	1	1
ELF1	-0.015	0.089	-9999	-0.37	8	8
CCNA2	-0.055	0.18	-9999	-0.52	66	66
PIK3CA	0.014	0.027	-9999	-0.59	1	1
JAK3	-0.056	0.18	-9999	-0.53	67	67
PIK3R1	0.015	0.001	-9999	-10000	0	0
JAK1	0.015	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.025	0.16	-9999	-0.43	31	31
SHC1	0.01	0.05	-9999	-0.49	5	5
SP1	0.016	0.044	-9999	-0.34	4	4
IL2RA	-0.041	0.17	-9999	-0.45	72	72
IL2RB	-0.093	0.22	-9999	-0.53	102	102
SOS1	0.015	0.001	-9999	-10000	0	0
IL2RG	-0.041	0.16	-9999	-0.52	54	54
G1/S transition of mitotic cell cycle	-0.034	0.18	-9999	-0.5	45	45
PTPN11	0.015	0.001	-9999	-10000	0	0
CCND2	0.019	0.095	-9999	-0.54	13	13
LCK	-0.08	0.21	-9999	-0.53	89	89
GRB2	0.014	0.022	-9999	-0.49	1	1
IL2	0.001	0.003	-9999	-10000	0	0
CDK6	-0.032	0.15	-9999	-0.54	43	43
CCND3	-0.011	0.14	-9999	-0.5	5	5

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.062	0.15	0.4	79	-10000	0	79
KIRREL	-0.036	0.16	-10000	0	-0.59	40	40
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.062	0.15	-10000	0	-0.4	79	79
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.045	0.11	-10000	0	-0.34	41	41
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.004	0.095	-10000	0	-0.44	5	5
FYN	-0.023	0.11	-10000	0	-0.32	41	41
mol:Ca2+	-0.044	0.11	-10000	0	-0.33	41	41
mol:DAG	-0.045	0.11	-10000	0	-0.34	41	41
NPHS2	-0.006	0.039	-10000	0	-0.54	2	2
mol:IP3	-0.045	0.11	-10000	0	-0.34	41	41
regulation of endocytosis	-0.014	0.1	-10000	0	-0.5	4	4
Nephrin/NEPH1/podocin/Cholesterol	-0.046	0.11	-10000	0	-0.34	41	41
establishment of cell polarity	-0.062	0.15	-10000	0	-0.4	79	79
Nephrin/NEPH1/podocin/NCK1-2	-0.04	0.098	-10000	0	-0.53	5	5
Nephrin/NEPH1/beta Arrestin2	-0.013	0.1	-10000	0	-0.5	4	4
NPHS1	-0.034	0.14	-10000	0	-0.5	43	43
Nephrin/NEPH1/podocin	-0.026	0.11	-10000	0	-0.32	41	41
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.013	0.027	-10000	0	-0.59	1	1
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.045	0.11	-10000	0	-0.34	41	41
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.045	0.11	-10000	0	-0.34	41	41
GRB2	0.013	0.022	-10000	0	-0.49	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.042	0.13	-10000	0	-0.34	54	54
cytoskeleton organization	-0.003	0.11	-10000	0	-0.48	6	6
Nephrin/NEPH1	-0.044	0.11	-10000	0	-0.29	74	74
Nephrin/NEPH1/ZO-1	-0.048	0.12	-10000	0	-0.36	40	40

×

Noncanonical Wnt signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.068	0.2	-9999	-0.55	74	74
GNB1/GNG2	-0.014	0.12	-9999	-0.42	20	20
mol:DAG	-0.004	0.12	-9999	-0.38	20	20
PLCG1	-0.005	0.12	-9999	-0.39	20	20
YES1	-0.022	0.13	-9999	-0.43	23	23
FZD3	0.011	0.046	-9999	-0.59	3	3
FZD6	-0.016	0.12	-9999	-0.49	31	31
G protein	-0.005	0.12	-9999	-0.39	20	20
MAP3K7	-0.098	0.16	-9999	-0.41	45	45
mol:Ca2+	-0.004	0.11	-9999	-0.37	20	20
mol:IP3	-0.004	0.12	-9999	-0.38	20	20
NLK	-0.005	0.011	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.11	0.17	-9999	-0.41	60	60
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.031	0.13	-9999	-0.3	77	77
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.02	0.12	-9999	-0.38	25	25
GO:0007205	-0.004	0.11	-9999	-0.38	19	19
WNT6	-0.034	0.16	-9999	-0.53	45	45
WNT4	-0.032	0.15	-9999	-0.52	45	45
NFAT1/CK1 alpha	-0.038	0.16	-9999	-0.44	37	37
GNG2	0.009	0.053	-9999	-0.59	4	4
WNT5A	-0.013	0.12	-9999	-0.56	24	24
WNT11	-0.017	0.13	-9999	-0.54	29	29
CDC42	-0.013	0.12	-9999	-0.41	22	22

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.071	0.14	-9999	-0.37	79	79
MAP4K1	-0.018	0.14	-9999	-0.58	28	28
MAP3K8	-0.006	0.1	-9999	-0.51	20	20
PRKCB	-0.061	0.19	-9999	-0.52	72	72
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.013	0.022	-9999	-0.49	1	1
MAP3K1	-0.004	0.11	-9999	-0.43	8	8
JUN	-0.028	0.16	-9999	-0.56	36	36
MAP3K7	0	0.1	-9999	-0.44	7	7
GRAP2	-0.047	0.17	-9999	-0.53	57	57
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0.003	0.11	-9999	-0.41	11	11
LAT	-0.017	0.13	-9999	-0.59	27	27
LCP2	-0.001	0.086	-9999	-0.5	15	15
MAPK8	-0.033	0.16	-9999	-0.59	35	35
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.01	0.11	-9999	-0.36	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.066	0.13	-9999	-0.54	16	16

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.009	0.053	-10000	0	-0.59	4	4
HDAC4	0.014	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.027	0.038	0.34	3	-10000	0	3
CDKN1A	-0.054	0.18	-10000	0	-0.48	61	61
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.004	0.04	0.45	4	-10000	0	4
FOXO1	0.011	0.044	-10000	0	-0.56	3	3
FOXO4	0.022	0.031	-10000	0	-0.29	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	-0.082	0.21	-10000	0	-0.53	90	90
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.12	0.2	-10000	0	-0.39	177	177
PPARGC1A	-0.011	0.12	-10000	0	-0.57	22	22
FHL2	-0.03	0.15	-10000	0	-0.52	43	43
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.013	0.036	-10000	0	-10000	0	0
HIST2H4A	0.028	0.038	-10000	0	-0.34	3	3
SIRT1/FOXO3a	0.013	0.04	0.29	4	-10000	0	4
SIRT1	0.016	0.046	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.011	0.04	-10000	0	-0.28	2	2
SIRT1/Histone H1b	-0.002	0.07	-10000	0	-0.25	20	20
apoptosis	-0.012	0.035	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.004	0.08	-10000	0	-0.35	22	22
p53/SIRT1	0.024	0.12	0.4	20	-0.43	13	33
SIRT1/FOXO4	0.012	0.046	-10000	0	-0.24	5	5
FOXO1/FHL2/SIRT1	-0.014	0.088	-10000	0	-0.28	40	40
HIST1H1E	0.003	0.073	-10000	0	-0.3	20	20
SIRT1/p300	0.009	0.053	-10000	0	-0.43	4	4
muscle cell differentiation	0.1	0.16	0.32	176	-10000	0	176
TP53	-0.001	0.11	-10000	0	-0.56	15	15
KU70/SIRT1/BAX	0.012	0.035	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.012	0.031	-10000	0	-0.49	2	2
HIV-1 Tat/SIRT1	-0.056	0.15	-10000	0	-0.38	90	90
ACSS2	0.03	0.025	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.1	0.16	-10000	0	-0.32	176	176

×

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	0.014	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.005	0.043	-9999	-0.54	2	2
Syndecan-3/Neurocan	-0.021	0.082	-9999	-0.32	31	31
POMC	-0.005	0.1	-9999	-0.54	18	18
EGFR	-0.083	0.21	-9999	-0.55	89	89
Syndecan-3/EGFR	-0.047	0.1	-9999	-0.27	90	90
AGRP	0.005	0.05	-9999	-0.49	5	5
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.014	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.026	0.15	-9999	-0.58	35	35
long-term memory	-0.002	0.026	-9999	-0.56	1	1
Syndecan-3/IL8	-0.082	0.12	-9999	-0.3	68	68
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
limb bud formation	-0.002	0.029	-9999	-0.62	1	1
MC4R	-0.11	0.24	-9999	-0.56	112	112
SRC	0.014	0	-9999	-10000	0	0
PTN	0.007	0.062	-9999	-0.52	7	7
FGFR/FGF/Syndecan-3	-0.002	0.03	-9999	-0.63	1	1
neuron projection morphogenesis	-0.021	0.08	-9999	-0.57	4	4
Syndecan-3/AgRP	-0.004	0.036	-9999	-0.29	6	6
Syndecan-3/AgRP/MC4R	-0.06	0.12	-9999	-0.29	77	77
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.002	0.03	-9999	-0.64	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.081	0.12	-9999	-0.3	68	68
IL8	-0.16	0.26	-9999	-0.53	162	162
Syndecan-3/Fyn/Cortactin	-0.002	0.027	-9999	-0.57	1	1
Syndecan-3/CASK	-0.002	0.028	-9999	-0.6	1	1
alpha-MSH/MC4R	-0.1	0.18	-9999	-0.42	123	123
Gamma Secretase	0	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.003	0.058	-10000	0	-0.58	4	4
AES	0.01	0.022	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.001	0.041	-10000	0	-0.34	7	7
SMAD4	0.014	0	-10000	0	-10000	0	0
DKK2	-0.11	0.23	-10000	0	-0.54	117	117
TLE1	0.008	0.044	-10000	0	-0.6	2	2
MACF1	0.015	0	-10000	0	-10000	0	0
CTNNB1	0.06	0.083	-10000	0	-10000	0	0
WIF1	-0.28	0.28	-10000	0	-0.54	269	269
beta catenin/RanBP3	0.02	0.11	0.39	33	-10000	0	33
KREMEN2	-0.052	0.18	-10000	0	-0.53	63	63
DKK1	-0.12	0.24	-10000	0	-0.53	124	124
beta catenin/beta TrCP1	0.066	0.078	-10000	0	-10000	0	0
FZD1	0.009	0.054	-10000	0	-0.49	6	6
AXIN2	-0.002	0.11	-10000	0	-0.9	5	5
AXIN1	0.015	0.001	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.023	0.044	-10000	0	-0.56	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.09	0.052	0.3	2	-10000	0	2
Axin1/APC/GSK3	0.008	0.037	0.24	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.051	0.068	-10000	0	-0.34	1	1
HNF1A	0.006	0.036	-10000	0	-0.6	1	1
CTBP1	0.007	0.024	0.2	1	-10000	0	1
MYC	-0.05	0.3	-10000	0	-1.4	22	22
RANBP3	0.014	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	163	163
NKD1	-0.004	0.099	-10000	0	-0.54	17	17
TCF4	0.006	0.034	-10000	0	-0.55	1	1
TCF3	0.005	0.04	-10000	0	-0.53	2	2
WNT1/LRP6/FZD1/Axin1	-0.02	0.073	-10000	0	-0.5	1	1
Ran/GTP	0.002	0.005	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.034	0.13	0.49	31	-10000	0	31
LEF1	0.002	0.054	-10000	0	-0.49	5	5
DVL1	0.06	0.046	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.086	0.079	-10000	0	-0.41	3	3
DKK1/LRP6/Kremen 2	-0.11	0.17	-10000	0	-0.34	168	168
LRP6	0.014	0.022	-10000	0	-0.49	1	1
CSNK1A1	0.009	0.026	-10000	0	-10000	0	0
NLK	0.012	0.033	-10000	0	-0.51	2	2
CCND1	-0.036	0.24	-10000	0	-1.4	13	13
WNT1	-0.028	0.13	-10000	0	-0.49	40	40
GSK3A	0.015	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
FRAT1	0.01	0.049	-10000	0	-0.54	4	4
PPP2R5D	0.043	0.049	0.27	17	-10000	0	17
APC	0.019	0.078	-10000	0	-0.38	2	2
WNT1/LRP6/FZD1	0.096	0.1	0.24	123	-10000	0	123
CREBBP	0.007	0.024	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.036	0.16	-9999	-0.46	60	60
KLHL20	-0.027	0.056	-9999	-0.27	9	9
CYFIP2	0.008	0.06	-9999	-0.54	6	6
Rac1/GDP	0.007	0.11	-9999	-10000	0	0
ENAH	-0.036	0.16	-9999	-0.46	60	60
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.013	0.022	-9999	-0.49	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.036	0.067	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.017	0.039	-9999	-0.18	11	11
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.093	0.15	-9999	-0.38	74	74
RAPGEF1	-0.015	0.15	-9999	-0.39	60	60
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.074	0.16	-9999	-0.48	60	60
CRK	-0.025	0.16	-9999	-0.42	60	60
E-cadherin/gamma catenin/alpha catenin	-0.085	0.15	-9999	-0.32	134	134
alphaE/beta7 Integrin	-0.033	0.11	-9999	-0.38	44	44
IQGAP1	0.004	0.076	-9999	-0.53	10	10
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.018	-9999	-0.32	1	1
DLG1	-0.036	0.16	-9999	-0.46	61	61
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.026	0.048	-9999	-10000	0	0
MLLT4	0.013	0.027	-9999	-0.59	1	1
ARF6/GTP/NME1/Tiam1	0	0.015	-9999	-0.32	1	1
PI3K	-0.033	0.061	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.1	0.18	-9999	-0.39	134	134
TIAM1	0.013	0.027	-9999	-0.59	1	1
E-cadherin(dimer)/Ca2+	-0.065	0.11	-9999	-0.3	60	60
AKT1	-0.019	0.035	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.54	127	127
RhoA/GDP	0.007	0.11	-9999	-10000	0	0
actin cytoskeleton organization	-0.02	0.041	-9999	-0.19	9	9
CDC42/GDP	0.007	0.11	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.033	0.11	-9999	-0.27	66	66
ITGB7	-0.033	0.16	-9999	-0.54	44	44
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.042	0.14	-9999	-0.32	60	60
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.067	0.12	-9999	-0.31	60	60
mol:GDP	-0.003	0.12	-9999	-0.32	8	8
CDC42/GTP/IQGAP1	-0.006	0.044	-9999	-0.32	10	10
JUP	0.003	0.081	-9999	-0.57	10	10
p120 catenin/RhoA/GDP	-0.043	0.086	-9999	-10000	0	0
RAC1/GTP/IQGAP1	-0.006	0.044	-9999	-0.32	10	10
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.01	0.063	-9999	-0.21	29	29
NME1	0.014	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.036	0.16	-9999	-0.46	60	60
regulation of cell-cell adhesion	-0.032	0.059	-9999	-10000	0	0
WASF2	-0.008	0.02	-9999	-10000	0	0
Rap1/GTP	-0.042	0.077	-9999	-0.32	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.091	0.15	-9999	-0.57	20	20
CCND1	0.01	0.077	-9999	-0.26	29	29
VAV2	-0.019	0.15	-9999	-0.42	60	60
RAP1/GDP	-0.04	0.081	-9999	-10000	0	0
adherens junction assembly	-0.034	0.16	-9999	-0.44	60	60
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
PIP5K1C	0.014	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.052	0.16	-9999	-0.55	20	20
E-cadherin/beta catenin	-0.068	0.13	-9999	-0.38	60	60
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.037	0.16	-9999	-0.46	60	60
PIK3CA	0.013	0.027	-9999	-0.59	1	1
Rac1/GTP	-0.042	0.09	-9999	-0.45	9	9
E-cadherin/beta catenin/alpha catenin	-0.078	0.14	-9999	-0.32	127	127
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.076	0.16	-9999	-0.49	60	60

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.008	0.06	-10000	0	-0.59	5	5
ANTXR2	0.002	0.079	-10000	0	-0.51	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.012	-10000	0	-0.066	17	17
monocyte activation	-0.16	0.25	-10000	0	-0.51	145	145
MAP2K2	-0.001	0.004	-10000	0	-10000	0	0
MAP2K1	-0.002	0.017	-10000	0	-0.32	1	1
MAP2K7	-0.002	0.01	-10000	0	-10000	0	0
MAP2K6	-0.002	0.017	-10000	0	-0.32	1	1
CYAA	0.007	0.052	-10000	0	-0.27	17	17
MAP2K4	-0.003	0.022	-10000	0	-0.32	2	2
IL1B	-0.082	0.14	-10000	0	-0.28	173	173
Channel	-0.01	0.052	-10000	0	-0.29	17	17
NLRP1	-0.003	0.022	-10000	0	-0.32	2	2
CALM1	0.012	0.035	-10000	0	-0.54	2	2
negative regulation of phagocytosis	-0.004	0.028	-10000	0	-0.54	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.012	0.066	17	-10000	0	17
MAPK3	-0.002	0.01	-10000	0	-10000	0	0
MAPK1	-0.002	0.01	-10000	0	-10000	0	0
PGR	-0.035	0.099	-10000	0	-0.32	53	53
PA/Cellular Receptors	-0.011	0.058	-10000	0	-0.32	17	17
apoptosis	-0.002	0.012	-10000	0	-0.066	17	17
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.009	0.051	-10000	0	-0.26	17	17
macrophage activation	0.019	0.011	-10000	0	-10000	0	0
TNF	-0.15	0.26	-10000	0	-0.54	156	156
VCAM1	-0.16	0.26	-10000	0	-0.51	145	145
platelet activation	-0.004	0.028	-10000	0	-0.54	1	1
MAPKKK cascade	-0.015	0.017	0.18	2	-10000	0	2
IL18	-0.009	0.088	-10000	0	-0.29	41	41
negative regulation of macrophage activation	-0.002	0.012	-10000	0	-0.066	17	17
LEF	-0.002	0.012	-10000	0	-0.066	17	17
CASP1	-0.004	0.022	-10000	0	-0.27	2	2
mol:cAMP	-0.004	0.028	-10000	0	-0.55	1	1
necrosis	-0.002	0.012	-10000	0	-0.066	17	17
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.008	0.053	-10000	0	-0.27	17	17
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.037	0.16	-10000	0	-0.52	14	14
UGCG	-0.022	0.14	-10000	0	-0.67	20	20
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.038	0.16	-10000	0	-0.4	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.021	0.14	-10000	0	-0.66	20	20
mol:DAG	-0.004	0.043	-10000	0	-0.97	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.069	0.12	-10000	0	-0.45	27	27
FRAP1	-0.026	0.18	-10000	0	-0.53	26	26
FOXO3	-0.018	0.17	-10000	0	-0.48	27	27
AKT1	-0.029	0.18	-10000	0	-0.46	42	42
GAB2	0.013	0.027	-10000	0	-0.6	1	1
SMPD1	0.004	0.036	-10000	0	-10000	0	0
SGMS1	0.003	0.046	-10000	0	-0.67	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0.018	-10000	0	-0.36	1	1
CALM1	0.012	0.035	-10000	0	-0.54	2	2
cell proliferation	-0.014	0.11	-10000	0	-0.3	43	43
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.024	0.021	-10000	0	-0.42	1	1
RPS6KB1	-0.004	0.064	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.043	-10000	0	-0.97	1	1
natural killer cell activation	0	0.002	-10000	0	-0.012	1	1
JAK3	-0.054	0.18	-10000	0	-0.53	67	67
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.016	0.003	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	-0.038	0.24	-10000	0	-0.93	25	25
MYB	-0.093	0.34	-10000	0	-1	53	53
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.036	0.17	-10000	0	-0.4	58	58
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.013	0.06	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.16	-10000	0	-0.39	58	58
Rac1/GDP	0.028	0.017	-10000	0	-0.32	1	1
T cell proliferation	-0.036	0.18	-10000	0	-0.46	46	46
SHC1	0.009	0.05	-10000	0	-0.49	5	5
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.02	-10000	0	-0.05	72	72
PRKCZ	-0.038	0.18	-10000	0	-0.48	46	46
NF kappa B1 p50/RelA	-0.062	0.12	-10000	0	-0.48	21	21
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.051	0.17	-10000	0	-0.43	58	58
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.062	0.18	-10000	0	-0.5	71	71
IL2RB	-0.092	0.22	-10000	0	-0.53	102	102
TERT	-0.082	0.21	-10000	0	-0.56	81	81
E2F1	-0.031	0.15	-10000	0	-0.43	55	55
SOS1	0.014	0.003	-10000	0	-10000	0	0
RPS6	0.013	0.022	-10000	0	-0.49	1	1
mol:cAMP	0.001	0.01	0.024	72	-10000	0	72
PTPN11	0.014	0.004	-10000	0	-10000	0	0
IL2RG	-0.04	0.16	-10000	0	-0.52	54	54
actin cytoskeleton organization	-0.036	0.18	-10000	0	-0.46	46	46
GRB2	0.013	0.022	-10000	0	-0.49	1	1
IL2	0.003	0.004	-10000	0	-10000	0	0
PIK3CA	0.015	0.027	-10000	0	-0.59	1	1
Rac1/GTP	0.032	0.022	-10000	0	-0.3	1	1
LCK	-0.079	0.21	-10000	0	-0.53	89	89
BCL2	-0.014	0.18	-10000	0	-0.62	20	20

×

IL27-mediated signaling events

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
TGFB1	0.004	0.08	-10000	0	-0.59	9	9
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.004	0.1	0.44	6	-10000	0	6
IL27/IL27R/JAK1	-0.034	0.15	-10000	0	-0.86	1	1
TBX21	-0.057	0.21	-10000	0	-0.56	36	36
IL12B	-0.002	0.054	-10000	0	-0.5	6	6
IL12A	-0.012	0.1	-10000	0	-0.42	29	29
IL6ST	-0.03	0.16	-10000	0	-0.6	37	37
IL27RA/JAK1	0.019	0.036	-10000	0	-10000	0	0
IL27	-0.016	0.11	-10000	0	-0.49	27	27
TYK2	0.015	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.054	0.12	-10000	0	-0.72	2	2
T-helper 2 cell differentiation	0.004	0.1	0.44	6	-10000	0	6
T cell proliferation during immune response	0.004	0.1	0.44	6	-10000	0	6
MAPKKK cascade	-0.004	0.1	-10000	0	-0.44	6	6
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.01	0.044	-10000	0	-0.49	4	4
STAT1	-0.002	0.088	-10000	0	-0.49	16	16
IL12RB1	-0.032	0.16	-10000	0	-0.56	42	42
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.085	0.24	-10000	0	-0.55	53	53
IL27/IL27R/JAK2/TYK2	-0.005	0.1	-10000	0	-0.44	6	6
positive regulation of T cell mediated cytotoxicity	-0.004	0.1	-10000	0	-0.44	6	6
STAT1 (dimer)	-0.059	0.24	0.52	27	-0.74	10	37
JAK2	0.015	0.004	-10000	0	-10000	0	0
JAK1	0.014	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	0.002	0.1	-10000	0	-0.54	1	1
T cell proliferation	-0.067	0.16	-10000	0	-0.51	14	14
IL12/IL12R/TYK2/JAK2	-0.006	0.094	-10000	0	-0.56	5	5
IL17A	-0.054	0.12	-10000	0	-0.72	2	2
mast cell activation	0.004	0.1	0.44	6	-10000	0	6
IFNG	0.001	0.021	-10000	0	-0.091	4	4
T cell differentiation	-0.004	0.005	-10000	0	-0.022	4	4
STAT3 (dimer)	0.004	0.097	-10000	0	-0.46	2	2
STAT5A (dimer)	-0.003	0.11	-10000	0	-0.52	6	6
STAT4 (dimer)	-0.084	0.17	-10000	0	-0.5	21	21
STAT4	-0.16	0.26	-10000	0	-0.53	161	161
T cell activation	-0.009	0.007	0.061	3	-10000	0	3
IL27R/JAK2/TYK2	-0.012	0.089	-10000	0	-10000	0	0
GATA3	-0.16	0.41	-10000	0	-1.4	51	51
IL18	-0.02	0.11	-10000	0	-0.4	41	41
positive regulation of mast cell cytokine production	0.004	0.096	-10000	0	-0.43	3	3
IL27/EBI3	-0.02	0.12	-10000	0	-0.4	46	46
IL27RA	0.014	0.034	-10000	0	-10000	0	0
IL6	-0.13	0.24	-10000	0	-0.52	134	134
STAT5A	0.001	0.088	-10000	0	-0.59	11	11
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.001	0.02	-10000	0	-10000	0	0
IL1B	-0.12	0.19	-10000	0	-0.39	173	173
EBI3	-0.012	0.12	-10000	0	-0.57	22	22
TNF	-0.11	0.19	-10000	0	-0.39	156	156

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-10000	0	-0.49	3	3
Jak2/Leptin Receptor	-0.009	0.1	0.2	17	-0.43	12	29
PTP1B/AKT1	-0.006	0.085	-10000	0	-0.33	9	9
FYN	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.015	0.093	-10000	0	-0.3	21	21
EGFR	-0.084	0.22	-10000	0	-0.55	89	89
EGF/EGFR	-0.096	0.16	-10000	0	-0.38	97	97
CSF1	-0.006	0.11	-10000	0	-0.59	17	17
AKT1	0.014	0.002	-10000	0	-10000	0	0
INSR	0.014	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.007	0.09	-10000	0	-0.36	10	10
Insulin Receptor/Insulin	-0.025	0.059	-10000	0	-0.32	6	6
HCK	-0.007	0.11	-10000	0	-0.54	20	20
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.006	0.089	-10000	0	-0.32	12	12
EGF	-0.052	0.18	-10000	0	-0.56	58	58
YES1	0.009	0.053	-10000	0	-0.59	4	4
CAV1	-0.031	0.12	-10000	0	-0.34	35	35
TXN	0.011	0.023	-10000	0	-0.5	1	1
PTP1B/IRS1/GRB2	-0.002	0.085	-10000	0	-0.33	9	9
cell migration	0.015	0.093	0.3	21	-10000	0	21
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	-0.019	0.14	-10000	0	-0.55	31	31
ITGA2B	-0.043	0.17	-10000	0	-0.57	50	50
CSF1R	-0.022	0.14	-10000	0	-0.57	32	32
Prolactin Receptor/Prolactin	-0.017	0.1	-10000	0	-0.4	33	33
FGR	0.011	0.038	-10000	0	-0.49	3	3
PTP1B/p130 Cas	-0.008	0.09	-10000	0	-0.35	10	10
Crk/p130 Cas	-0.002	0.085	-10000	0	-0.34	9	9
DOK1	0.002	0.085	-10000	0	-0.33	9	9
JAK2	0.001	0.084	-10000	0	-0.35	12	12
Jak2/Leptin Receptor/Leptin	-0.11	0.18	-10000	0	-0.43	99	99
PIK3R1	0.014	0	-10000	0	-10000	0	0
PTPN1	-0.015	0.094	-10000	0	-0.3	21	21
LYN	0.004	0.073	-10000	0	-0.51	10	10
CDH2	0.013	0.027	-10000	0	-0.59	1	1
SRC	0.012	0.038	-10000	0	-10000	0	0
ITGB3	-0.053	0.18	-10000	0	-0.51	65	65
CAT1/PTP1B	-0.06	0.15	-10000	0	-0.4	44	44
CAPN1	0.014	0.027	-10000	0	-0.6	1	1
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.018	0.053	-10000	0	-0.35	2	2
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.11	0.18	-10000	0	-0.43	103	103
negative regulation of transcription	0.001	0.083	-10000	0	-0.34	13	13
FCGR2A	-0.031	0.15	-10000	0	-0.54	42	42
FER	-0.013	0.12	-10000	0	-0.6	22	22
alphaIIb/beta3 Integrin	-0.082	0.17	-10000	0	-0.41	107	107
BLK	-0.11	0.22	-10000	0	-0.52	114	114
Insulin Receptor/Insulin/Shc	-0.003	0.045	-10000	0	-0.32	10	10
RHOA	0.015	0.002	-10000	0	-10000	0	0
LEPR	0.001	0.09	-10000	0	-0.53	14	14
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
p210 bcr-abl/Grb2	0.013	0.022	-10000	0	-0.49	1	1
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.069	0.16	-10000	0	-0.43	49	49
PRL	0.002	0.031	-10000	0	-0.48	2	2
SOCS3	-0.14	0.34	-10000	0	-1.4	31	31
SPRY2	0.006	0.064	-10000	0	-0.5	8	8
Insulin Receptor/Insulin/IRS1	0	0.035	-10000	0	-0.34	5	5
CSF1/CSF1R	-0.03	0.14	-10000	0	-0.4	45	45
Ras protein signal transduction	0.02	0.034	-10000	0	-0.4	1	1
IRS1	0.014	0	-10000	0	-10000	0	0
INS	-0.005	0.056	-10000	0	-0.57	5	5
LEP	-0.002	0.058	-10000	0	-0.49	7	7
STAT5B	-0.003	0.084	-10000	0	-0.28	16	16
STAT5A	-0.007	0.088	-10000	0	-0.3	17	17
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PDGFB-D/PDGFRB	-0.008	0.092	-10000	0	-0.33	15	15
CSN2	-0.001	0.042	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
LAT	-0.038	0.15	-10000	0	-0.48	46	46
YBX1	0.02	0.038	-10000	0	-0.58	2	2
LCK	-0.081	0.21	-10000	0	-0.54	89	89
SHC1	0.009	0.05	-10000	0	-0.49	5	5
NOX4	-0.067	0.19	-10000	0	-0.52	77	77

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.007	0.1	-10000	0	-0.35	44	44
MAP4K4	-0.022	0.12	-10000	0	-0.46	17	17
BAG4	-0.001	0.095	-10000	0	-0.59	13	13
PKC zeta/ceramide	-0.013	0.073	0.15	5	-0.26	26	31
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BAX	0.006	0.025	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.014	-10000	0	-10000	0	0
BAD	0.003	0.048	0.16	9	-10000	0	9
SMPD1	-0.027	0.089	-10000	0	-0.2	81	81
RB1	0.003	0.051	0.16	9	-0.4	1	10
FADD/Caspase 8	-0.013	0.12	-10000	0	-0.42	20	20
MAP2K4	0.006	0.057	-10000	0	-0.26	8	8
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.011	0.045	-10000	0	-10000	0	0
EGF	-0.05	0.18	-10000	0	-0.56	58	58
mol:ceramide	-0.006	0.052	0.14	39	-10000	0	39
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.007	0.1	-10000	0	-0.35	44	44
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.002	0.051	0.16	9	-0.4	1	10
cell proliferation	-0.002	0.092	-10000	0	-0.33	31	31
BID	-0.01	0.091	-10000	0	-0.41	9	9
MAP3K1	0	0.057	0.16	9	-0.27	7	16
EIF2A	0.015	0.052	-10000	0	-0.28	5	5
TRADD	0.013	0.027	-10000	0	-0.59	1	1
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.022	0.043	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.043	-10000	0	-10000	0	0
Cathepsin D/ceramide	0.001	0.046	0.15	8	-10000	0	8
FADD	-0.022	0.12	-10000	0	-0.46	17	17
KSR1	0.003	0.048	0.16	9	-10000	0	9
MAPK8	-0.003	0.073	0.16	4	-0.25	26	30
PRKRA	0.003	0.048	0.16	9	-10000	0	9
PDGFA	-0.029	0.14	-10000	0	-0.5	44	44
TRAF2	0.014	0	-10000	0	-10000	0	0
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.006	0.051	0.14	39	-10000	0	39
CTSD	0.013	0.022	-10000	0	-0.49	1	1
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0	0.1	-10000	0	-0.36	31	31
PRKCD	-0.018	0.14	-10000	0	-0.59	27	27
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.007	0.1	-10000	0	-0.35	44	44
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.034	0.16	-10000	0	-0.53	45	45
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.032	0.13	-10000	0	-0.49	17	17
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-10000	0	-0.34	171	171
mol:Sphingosine-1-phosphate	-0.007	0.1	-10000	0	-0.34	44	44
MAP2K1	0.018	0.045	-10000	0	-0.23	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	0.008	0.038	0.19	4	-10000	0	4
TNFRSF1A	0.001	0.086	-10000	0	-0.55	12	12
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.02	0.093	-10000	0	-0.44	23	23
EIF2AK2	0.007	0.055	-10000	0	-0.3	5	5
TNF-alpha/TNFR1A/FAN	-0.1	0.15	-10000	0	-0.32	165	165
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.081	-10000	0	-0.32	10	10
MAP2K2	0.018	0.043	-10000	0	-10000	0	0
SMPD3	-0.046	0.13	-10000	0	-0.26	107	107
TNF	-0.15	0.26	-10000	0	-0.54	156	156
PKC zeta/PAR4	-0.053	0.14	-10000	0	-0.4	67	67
mol:PHOSPHOCHOLINE	0.007	0.077	0.21	49	-10000	0	49
NF kappa B1/RelA/I kappa B alpha	-0.035	0.095	-10000	0	-0.32	34	34
AIFM1	0.008	0.038	0.19	4	-10000	0	4
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.026	0.11	-10000	0	-0.26	68	68
epithelial cell differentiation	-0.064	0.11	-10000	0	-0.3	60	60
CYFIP2	0.008	0.06	-10000	0	-0.54	6	6
ENAH	0.008	0.1	-10000	0	-0.32	7	7
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
EPHA2	-0.016	0.12	-10000	0	-0.5	30	30
MYO6	-0.029	0.12	-10000	0	-10000	0	0
CTNNB1	0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.034	-10000	0	-0.32	6	6
AQP5	-0.14	0.18	-10000	0	-0.51	73	73
CTNND1	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.028	0.12	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.034	0.13	-10000	0	-0.53	3	3
EGF	-0.05	0.18	-10000	0	-0.56	58	58
NCKAP1	0.014	0	-10000	0	-10000	0	0
AQP3	-0.076	0.12	-10000	0	-0.48	24	24
cortical microtubule organization	-0.064	0.11	-10000	0	-0.3	60	60
GO:0000145	-0.027	0.12	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.065	0.11	-10000	0	-0.3	60	60
MLLT4	0.013	0.027	-10000	0	-0.59	1	1
ARF6/GDP	-0.058	0.096	-10000	0	-0.4	11	11
ARF6	0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.017	0.066	-10000	0	-0.4	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.029	0.12	-10000	0	-0.35	10	10
PVRL2	0.012	0.035	-10000	0	-0.54	2	2
ZYX	-0.033	0.13	-10000	0	-0.52	1	1
ARF6/GTP	-0.015	0.059	-10000	0	-0.53	1	1
CDH1	-0.12	0.24	-10000	0	-0.54	127	127
EGFR/EGFR/EGF/EGF	-0.13	0.17	-10000	0	-0.52	47	47
RhoA/GDP	-0.059	0.1	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.022	0.12	-10000	0	-0.54	1	1
IGF-1R heterotetramer	0.013	0.022	-10000	0	-0.49	1	1
GIT1	0.014	0	-10000	0	-10000	0	0
IGF1R	0.013	0.022	-10000	0	-0.49	1	1
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
DIAPH1	-0.001	0.052	-10000	0	-0.65	3	3
Wnt receptor signaling pathway	0.064	0.11	0.3	60	-10000	0	60
RHOA	0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.058	0.097	-10000	0	-0.4	11	11
CTNNA1	0.014	0	-10000	0	-10000	0	0
VCL	-0.023	0.12	-10000	0	-0.56	1	1
EFNA1	0.01	0.044	-10000	0	-0.49	4	4
LPP	-0.043	0.14	-10000	0	-0.45	10	10
Ephrin A1/EPHA2	-0.07	0.11	-10000	0	-0.46	10	10
SEC6/SEC8	-0.051	0.092	-10000	0	-0.47	3	3
MGAT3	-0.035	0.13	-10000	0	-0.54	3	3
HGF/MET	-0.16	0.18	-10000	0	-0.51	74	74
HGF	-0.079	0.2	-10000	0	-0.51	91	91
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.026	0.11	-10000	0	-0.26	68	68
actin cable formation	0.019	0.1	-10000	0	-0.32	3	3
KIAA1543	-0.064	0.17	-10000	0	-0.55	25	25
KIFC3	-0.03	0.12	-10000	0	-0.58	1	1
NCK1	0.013	0.027	-10000	0	-0.59	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ACTN1	-0.046	0.14	-10000	0	-0.47	7	7
NCK1/GIT1	-0.001	0.019	-10000	0	-0.43	1	1
mol:GDP	-0.064	0.11	-10000	0	-0.3	60	60
EXOC4	0.014	0	-10000	0	-10000	0	0
STX4	-0.029	0.12	-10000	0	-10000	0	0
PIP5K1C	-0.029	0.12	-10000	0	-10000	0	0
LIMA1	0.004	0.08	-10000	0	-0.59	9	9
ABI1	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.003	0.11	-10000	0	-0.37	6	6
adherens junction assembly	-0.044	0.17	-10000	0	-0.52	25	25
IGF-1R heterotetramer/IGF1	-0.066	0.12	-10000	0	-0.54	8	8
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.031	-10000	0	-0.4	3	3
MET	-0.15	0.25	-10000	0	-0.53	150	150
PLEKHA7	-0.038	0.14	-10000	0	-0.56	6	6
mol:GTP	-0.017	0.065	-10000	0	-0.4	3	3
establishment of epithelial cell apical/basal polarity	0.003	0.12	-10000	0	-0.45	3	3
cortical actin cytoskeleton stabilization	-0.026	0.11	-10000	0	-0.26	68	68
regulation of cell-cell adhesion	-0.022	0.12	-10000	0	-0.54	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.026	0.11	-10000	0	-0.26	68	68

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.017	0.068	-10000	0	-0.36	3	3
epithelial cell differentiation	-0.042	0.085	-10000	0	-0.46	8	8
ITCH	0.019	0.013	-10000	0	-10000	0	0
WWP1	0.024	0.05	-10000	0	-10000	0	0
FYN	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
PRL	0	0.031	-10000	0	-0.49	2	2
neuron projection morphogenesis	-0.031	0.15	-10000	0	-0.46	12	12
PTPRZ1	0.004	0.077	-10000	0	-0.57	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.089	0.13	-10000	0	-0.47	17	17
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.078	0.17	-10000	0	-0.34	117	117
ADAM17	0.011	0.066	-10000	0	-0.58	6	6
ErbB4/ErbB4	0.02	0.064	-10000	0	-0.41	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.004	0.12	-10000	0	-0.38	39	39
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.065	0.16	-10000	0	-0.39	27	27
GRIN2B	-0.15	0.21	-10000	0	-0.5	82	82
ErbB4/ErbB2/betacellulin	-0.031	0.14	-10000	0	-0.42	21	21
STAT1	-0.002	0.088	-10000	0	-0.49	16	16
HBEGF	0.004	0.07	-10000	0	-0.49	10	10
PRLR	-0.02	0.14	-10000	0	-0.56	31	31
E4ICDs/ETO2	0.017	0.07	-10000	0	-0.37	8	8
axon guidance	-0.016	0.078	-10000	0	-0.34	3	3
NEDD4	0.007	0.08	-10000	0	-0.52	11	11
Prolactin receptor/Prolactin receptor/Prolactin	-0.026	0.099	-10000	0	-0.4	33	33
CBFA2T3	0.006	0.07	-10000	0	-0.59	7	7
ErbB4/ErbB2/HBEGF	0.022	0.075	-10000	0	-0.36	8	8
MAPK3	-0.041	0.15	-10000	0	-0.48	12	12
STAT1 (dimer)	0.013	0.075	-10000	0	-0.39	4	4
MAPK1	-0.041	0.15	-10000	0	-0.48	12	12
JAK2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.07	0.16	-10000	0	-0.4	32	32
NRG1	-0.11	0.21	-10000	0	-0.41	166	166
NRG3	-0.031	0.16	-10000	0	-0.59	38	38
NRG2	0.012	0.038	-10000	0	-0.59	2	2
NRG4	-0.042	0.16	-10000	0	-0.51	54	54
heart development	-0.016	0.078	-10000	0	-0.34	3	3
neural crest cell migration	-0.069	0.16	-10000	0	-0.4	32	32
ERBB2	0.016	0.069	-10000	0	-0.38	15	15
WWOX/E4ICDs	0.022	0.054	-10000	0	-0.36	1	1
SHC1	0.009	0.05	-10000	0	-0.49	5	5
ErbB4/EGFR/neuregulin 4	-0.055	0.16	-10000	0	-0.47	35	35
apoptosis	0.041	0.11	0.41	39	-10000	0	39
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.021	0.061	-10000	0	-0.44	3	3
ErbB4/ErbB2/epiregulin	0.005	0.086	-10000	0	-0.39	10	10
ErbB4/ErbB4/betacellulin/betacellulin	-0.041	0.14	-10000	0	-0.36	63	63
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.029	0.076	-10000	0	-0.47	4	4
MDM2	0.026	0.058	-10000	0	-0.36	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.096	0.14	-10000	0	-0.37	27	27
STAT5A	-0.013	0.091	-10000	0	-0.4	10	10
ErbB4/EGFR/neuregulin 1 beta	-0.12	0.2	-10000	0	-0.5	61	61
DLG4	0.004	0.07	-10000	0	-0.49	10	10
GRB2/SHC	-0.004	0.037	-10000	0	-0.34	6	6
E4ICDs/TAB2/NCoR1	-0.014	0.049	-10000	0	-0.55	2	2
STAT5A (dimer)	-0.044	0.091	-10000	0	-0.51	7	7
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.073	-10000	0	-0.33	2	2
LRIG1	-0.002	0.099	-10000	0	-0.59	14	14
EREG	-0.013	0.11	-10000	0	-0.49	24	24
BTC	-0.086	0.22	-10000	0	-0.56	88	88
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.016	0.079	-10000	0	-0.34	3	3
ERBB4	0.02	0.064	-10000	0	-0.41	1	1
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.036	0.13	-10000	0	-0.59	27	27
GRB2	0.013	0.022	-10000	0	-0.49	1	1
ErbB4/ErbB2/neuregulin 4	-0.004	0.11	-10000	0	-0.4	16	16
glial cell differentiation	0.014	0.048	0.54	2	-10000	0	2
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.1	0.19	-10000	0	-0.51	48	48

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.057	0.19	-10000	0	-0.57	62	62
HRAS	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
AKT	0.02	0.045	-10000	0	-0.38	4	4
FOXO3	0.014	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
FOXO1	0.011	0.044	-10000	0	-0.56	3	3
AKT3	0.008	0.06	-10000	0	-0.59	5	5
FOXO4	0.013	0.027	-10000	0	-0.59	1	1
MET	-0.15	0.25	-10000	0	-0.53	150	150
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PIK3CB	0.014	0	-10000	0	-10000	0	0
NRAS	0.014	0	-10000	0	-10000	0	0
PIK3CG	-0.059	0.19	-10000	0	-0.53	69	69
PIK3R3	0.011	0.041	-10000	0	-0.52	3	3
PIK3R2	0.014	0	-10000	0	-10000	0	0
NF1	0.012	0.038	-10000	0	-0.59	2	2
RAS	-0.054	0.11	0.22	1	-0.29	54	55
ERBB2	0.005	0.068	-10000	0	-0.5	9	9
proliferation/survival/translation	-0.008	0.051	0.22	7	-10000	0	7
PI3K	-0.046	0.11	-10000	0	-0.25	78	78
PIK3R1	0.014	0	-10000	0	-10000	0	0
KRAS	0.013	0.022	-10000	0	-0.49	1	1
FOXO	0.028	0.03	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
PTEN	0.013	0.027	-10000	0	-0.59	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.011	0.12	-10000	0	-0.41	20	20
CRKL	0.02	0.11	-10000	0	-0.42	20	20
HRAS	0.002	0.14	-10000	0	-0.47	15	15
mol:PIP3	0.003	0.1	0.22	1	-0.39	21	22
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.011	0.038	-10000	0	-0.49	3	3
GAB1	0.012	0.12	-10000	0	-0.45	20	20
FOXO3	0.025	0.1	-10000	0	-0.37	19	19
AKT1	0.017	0.11	-10000	0	-0.4	20	20
BAD	0.025	0.1	-10000	0	-0.38	18	18
megakaryocyte differentiation	0.006	0.12	-10000	0	-0.39	32	32
GSK3B	0.024	0.1	-10000	0	-0.39	19	19
RAF1	0.014	0.12	-10000	0	-0.38	14	14
SHC1	0.009	0.05	-10000	0	-0.49	5	5
STAT3	0.014	0.11	-10000	0	-0.44	20	20
STAT1	0.004	0.24	-10000	0	-0.91	27	27
HRAS/SPRED1	0.011	0.12	-10000	0	-0.38	14	14
cell proliferation	0.006	0.13	-10000	0	-0.42	30	30
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
TEC	-0.004	0.1	-10000	0	-0.54	17	17
RPS6KB1	0.013	0.11	-10000	0	-0.38	29	29
HRAS/SPRED2	0.01	0.12	-10000	0	-0.38	15	15
LYN/TEC/p62DOK	-0.038	0.12	-10000	0	-0.45	28	28
MAPK3	0.025	0.089	-10000	0	-0.26	13	13
STAP1	-0.004	0.13	-10000	0	-0.43	31	31
GRAP2	-0.047	0.17	-10000	0	-0.53	57	57
JAK2	-0.05	0.18	-10000	0	-0.74	27	27
STAT1 (dimer)	0.005	0.23	-10000	0	-0.89	27	27
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.057	0.13	-10000	0	-0.46	31	31
actin filament polymerization	0.007	0.12	-10000	0	-0.39	29	29
LYN	0.004	0.073	-10000	0	-0.51	10	10
STAP1/STAT5A (dimer)	-0.004	0.18	-10000	0	-0.6	30	30
PIK3R1	0.014	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.029	0.1	-10000	0	-0.38	18	18
PI3K	0.022	0.11	-10000	0	-0.42	20	20
PTEN	0.013	0.027	-10000	0	-0.59	1	1
SCF/KIT/EPO/EPOR	-0.004	0.28	-10000	0	-1.2	21	21
MAPK8	0.006	0.13	-10000	0	-0.43	30	30
STAT3 (dimer)	0.014	0.11	-10000	0	-0.43	20	20
positive regulation of transcription	0.026	0.077	-10000	0	-0.24	5	5
mol:GDP	-0.062	0.12	0.22	2	-0.43	31	33
PIK3C2B	0.009	0.12	-10000	0	-0.42	24	24
CBL/CRKL	0.027	0.11	-10000	0	-0.39	20	20
FER	0	0.14	-10000	0	-0.43	36	36
SH2B3	0.013	0.12	-10000	0	-0.44	20	20
PDPK1	0.01	0.1	-10000	0	-0.38	20	20
SNAI2	-0.007	0.14	-10000	0	-0.42	33	33
positive regulation of cell proliferation	0.01	0.18	-10000	0	-0.69	27	27
KITLG	0.004	0.093	-10000	0	-0.59	12	12
cell motility	0.01	0.18	-10000	0	-0.69	27	27
PTPN6	-0.012	0.097	-10000	0	-0.55	16	16
EPOR	0.038	0.078	-10000	0	-10000	0	0
STAT5A (dimer)	0.007	0.16	-10000	0	-0.58	29	29
SOCS1	-0.032	0.15	-10000	0	-0.51	45	45
cell migration	0.04	0.16	0.36	71	-10000	0	71
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.006	0.099	-10000	0	-0.5	20	20
VAV1	-0.019	0.14	-10000	0	-0.56	30	30
GRB10	0.012	0.12	-10000	0	-0.42	22	22
PTPN11	0.013	0.005	-10000	0	-10000	0	0
SCF/KIT	0.006	0.12	0.23	9	-0.39	31	40
GO:0007205	-0.002	0.006	-10000	0	-10000	0	0
MAP2K1	0.022	0.097	-10000	0	-0.29	13	13
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.01	0.27	-10000	0	-1.3	20	20
MAP2K2	0.022	0.097	-10000	0	-0.29	13	13
SHC/Grb2/SOS1	-0.028	0.092	-10000	0	-0.41	20	20
STAT5A	0.007	0.17	-10000	0	-0.6	29	29
GRB2	0.013	0.022	-10000	0	-0.49	1	1
response to radiation	-0.006	0.13	-10000	0	-0.42	33	33
SHC/GRAP2	-0.045	0.13	-10000	0	-0.39	60	60
PTPRO	0.005	0.13	-10000	0	-0.4	32	32
SH2B2	0.007	0.12	-10000	0	-0.39	29	29
DOK1	0.012	0.035	-10000	0	-0.54	2	2
MATK	-0.041	0.16	-10000	0	-0.37	71	71
CREBBP	0.039	0.012	-10000	0	-10000	0	0
BCL2	0.022	0.18	-10000	0	-1.3	8	8

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.092	-9999	-0.37	29	29
PDGFRB	0.01	0.039	-9999	-0.5	3	3
SPHK1	-0.042	0.14	-9999	-0.75	18	18
mol:S1P	-0.041	0.12	-9999	-0.61	21	21
S1P1/S1P/Gi	-0.021	0.15	-9999	-0.35	65	65
GNAO1	0.006	0.06	-9999	-0.6	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.01	0.14	-9999	-0.53	11	11
PLCG1	-0.014	0.15	-9999	-0.54	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.039	-9999	-0.5	3	3
GNAI2	0.012	0.006	-9999	-10000	0	0
GNAI3	0.012	0.006	-9999	-10000	0	0
GNAI1	-0.007	0.11	-9999	-0.59	16	16
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.003	0.079	-9999	-0.31	29	29
S1P1/S1P	-0.051	0.11	-9999	-0.45	28	28
negative regulation of cAMP metabolic process	-0.02	0.15	-9999	-0.34	65	65
MAPK3	-0.039	0.21	-9999	-0.53	61	61
calcium-dependent phospholipase C activity	-0.001	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.004	0.071	-9999	-0.53	9	9
PLCB2	-0.017	0.13	-9999	-0.46	25	25
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.042	0.094	-9999	-0.41	22	22
receptor internalization	-0.048	0.1	-9999	-0.42	28	28
PTGS2	-0.1	0.36	-9999	-1	62	62
Rac1/GTP	-0.042	0.094	-9999	-0.41	22	22
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	-0.009	0.1	-9999	-0.49	22	22
negative regulation of T cell proliferation	-0.02	0.15	-9999	-0.34	65	65
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.012	0.006	-9999	-10000	0	0
MAPK1	-0.039	0.21	-9999	-0.53	61	61
S1P1/S1P/PDGFB-D/PDGFRB	-0.011	0.13	-9999	-0.46	22	22
ABCC1	0.01	0.045	-9999	-0.49	4	4

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0	-9999	-10000	0	0
SPHK1	-0.029	0.15	-9999	-0.54	40	40
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.005	0.07	-9999	-0.3	20	20
GNAO1	0.008	0.06	-9999	-0.59	5	5
mol:Sphinganine-1-P	-0.007	0.11	-9999	-0.38	40	40
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.071	-9999	-0.5	4	4
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
S1PR3	-0.034	0.15	-9999	-0.52	47	47
S1PR2	0.007	0.062	-9999	-0.56	6	6
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.015	0.055	-9999	-0.26	20	20
S1PR5	-0.13	0.25	-9999	-0.55	132	132
S1PR4	0	0.086	-9999	-0.51	14	14
GNAI1	-0.005	0.1	-9999	-0.59	16	16
S1P/S1P5/G12	-0.062	0.15	-9999	-0.34	83	83
S1P/S1P3/Gq	-0.009	0.12	-9999	-0.48	15	15
S1P/S1P4/Gi	0.024	0.07	-9999	-0.37	6	6
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.014	0	-9999	-10000	0	0
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.56	19	19
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.004	0.08	-9999	-0.59	9	9
ABCC1	0.01	0.044	-9999	-0.49	4	4

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.052	0.099	0.51	8	-10000	0	8
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.086	0.15	-10000	0	-0.34	132	132
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.008	0.06	-10000	0	-0.59	5	5
RhoA/GTP	-0.053	0.1	-10000	0	-0.53	8	8
negative regulation of cAMP metabolic process	-0.033	0.13	-10000	0	-0.57	8	8
GNAZ	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.013	0.027	-10000	0	-0.59	1	1
S1PR5	-0.13	0.25	-10000	0	-0.55	132	132
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.033	0.13	-10000	0	-0.58	8	8
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16

×

Ephrin B reverse signaling

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
EFNB2	0.002	0.08	-10000	0	-0.52	12	12
EPHB2	-0.001	0.088	-10000	0	-0.52	14	14
EFNB1	-0.061	0.17	-10000	0	-0.37	110	110
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.076	0.14	-10000	0	-0.58	19	19
Ephrin B2/EPHB1-2	-0.034	0.12	-10000	0	-0.34	60	60
neuron projection morphogenesis	-0.073	0.13	-10000	0	-0.55	19	19
Ephrin B1/EPHB1-2/Tiam1	-0.053	0.17	-10000	0	-0.61	20	20
DNM1	-0.1	0.22	-10000	0	-0.52	109	109
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.011	0.082	-10000	0	-0.72	6	6
YES1	-0.009	0.11	-10000	0	-1	6	6
Ephrin B1/EPHB1-2/NCK2	-0.052	0.17	-10000	0	-0.61	19	19
PI3K	0.012	0.083	-10000	0	-0.67	7	7
mol:GDP	-0.075	0.16	-10000	0	-0.61	19	19
ITGA2B	-0.043	0.17	-10000	0	-0.57	50	50
endothelial cell proliferation	-0.005	0.048	-10000	0	-0.31	12	12
FYN	-0.008	0.1	-10000	0	-0.94	6	6
MAP3K7	-0.007	0.083	-10000	0	-0.76	6	6
FGR	-0.008	0.1	-10000	0	-0.94	6	6
TIAM1	0.013	0.027	-10000	0	-0.59	1	1
PIK3R1	0.014	0	-10000	0	-10000	0	0
RGS3	0.011	0.038	-10000	0	-0.49	3	3
cell adhesion	-0.034	0.14	-10000	0	-0.59	14	14
LYN	-0.009	0.1	-10000	0	-0.94	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.011	0.098	-10000	0	-0.91	6	6
Ephrin B1/EPHB1-2	-0.013	0.09	-10000	0	-0.82	6	6
SRC	-0.008	0.1	-10000	0	-0.94	6	6
ITGB3	-0.052	0.18	-10000	0	-0.51	65	65
EPHB1	-0.035	0.16	-10000	0	-0.59	41	41
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.004	0.048	-10000	0	-0.31	12	12
alphaIIb/beta3 Integrin	-0.085	0.17	-10000	0	-0.41	107	107
BLK	-0.028	0.11	-10000	0	-0.98	6	6
HCK	-0.012	0.11	-10000	0	-1	6	6
regulation of stress fiber formation	0.075	0.15	0.6	19	-10000	0	19
MAPK8	0.01	0.095	-10000	0	-0.72	6	6
Ephrin B1/EPHB1-2/RGS3	-0.054	0.17	-10000	0	-0.62	20	20
endothelial cell migration	-0.008	0.082	-10000	0	-0.54	9	9
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	0.003	0.082	-10000	0	-0.68	7	7
regulation of focal adhesion formation	0.075	0.15	0.6	19	-10000	0	19
chemotaxis	0.076	0.16	0.61	20	-10000	0	20
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
Rac1/GTP	-0.075	0.14	-10000	0	-0.57	19	19
angiogenesis	-0.013	0.089	-10000	0	-0.82	6	6
LCK	-0.026	0.11	-10000	0	-0.96	6	6

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	0.013	0.022	-10000	0	-0.49	1	1
NFATC1	0.029	0.095	-10000	0	-0.44	2	2
NFATC2	0.008	0.078	-10000	0	-0.26	19	19
NFATC3	0.007	0.082	-10000	0	-0.39	18	18
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.063	0.18	-10000	0	-0.52	42	42
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.15	0.19	-10000	0	-0.48	90	90
BCL2/BAX	-0.007	0.053	-10000	0	-0.43	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.026	-10000	0	-0.4	2	2
CaM/Ca2+	0.01	0.026	-10000	0	-0.4	2	2
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.003	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.054	0.17	-10000	0	-0.54	36	36
Calcineurin A alpha-beta B1/BCL2	0.005	0.075	-10000	0	-0.59	8	8
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.053	0.17	0.52	36	-10000	0	36
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.012	0.031	-10000	0	-0.49	2	2
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	-0.11	0.23	-10000	0	-0.53	117	117
MAP3K8	-0.007	0.1	-10000	0	-0.51	20	20
NFAT4/CK1 alpha	-0.014	0.057	-10000	0	-0.4	3	3
MEF2D/NFAT1/Cbp/p300	0.025	0.11	-10000	0	-0.43	13	13
CABIN1	-0.064	0.18	-10000	0	-0.52	42	42
CALM1	0.012	0.035	-10000	0	-0.54	2	2
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.007	0.059	-10000	0	-0.49	7	7
CAMK4	-0.17	0.27	-10000	0	-0.56	167	167
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	-0.009	0.11	-10000	0	-0.49	24	24
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.012	0.1	-10000	0	-0.35	45	45
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.095	-10000	0	-0.59	13	13
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.001	0.079	-10000	0	-0.49	13	13
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.037	0.1	-10000	0	-0.45	4	4
PRKCH	0.014	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.003	0.038	-10000	0	-0.43	4	4
CASP3	0.013	0.022	-10000	0	-0.49	1	1
PIM1	0.008	0.054	-10000	0	-0.49	6	6
Calcineurin A alpha-beta B1/FKBP12/FK506	0.01	0.003	-10000	0	-10000	0	0
apoptosis	-0.002	0.021	-10000	0	-0.34	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.076	-10000	0	-0.31	4	4
PRKCB	-0.061	0.19	-10000	0	-0.52	72	72
PRKCE	0.003	0.077	-10000	0	-0.52	11	11
JNK2/NFAT4	0.014	0.074	-10000	0	-0.36	17	17
BAD/BCL-XL	-0.001	0.015	-10000	0	-0.34	1	1
PRKCD	-0.018	0.14	-10000	0	-0.59	27	27
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
PRKCA	0.013	0.027	-10000	0	-0.59	1	1
PRKCG	-0.19	0.27	-10000	0	-0.54	190	190
PRKCQ	-0.005	0.11	-10000	0	-0.58	17	17
FKBP38/BCL2	-0.007	0.053	-10000	0	-0.43	8	8
EP300	0.01	0.053	-10000	0	-0.59	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.026	0.1	-10000	0	-0.45	3	3
CaM/Ca2+/FKBP38	0.018	0.023	-10000	0	-0.33	2	2
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.02	0.023	-10000	0	-0.33	2	2
CaM/Ca2+/CAMK IV	-0.1	0.17	-10000	0	-0.35	168	168
NFATc/ERK1	0.036	0.091	-10000	0	-0.49	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.15	0.19	-10000	0	-0.48	90	90
NR4A1	0.017	0.14	-10000	0	-0.47	35	35
GSK3B	0.013	0.027	-10000	0	-0.59	1	1
positive T cell selection	0.007	0.081	-10000	0	-0.39	18	18
NFAT1/CK1 alpha	-0.02	0.05	-10000	0	-0.36	4	4
RCH1/ KPNB1	-0.001	0.021	-10000	0	-0.34	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.003	-10000	0	-10000	0	0
AKAP5	-0.031	0.14	-10000	0	-0.5	45	45
MEF2D	0.012	0.032	-10000	0	-0.5	2	2
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.034	0.091	-10000	0	-0.49	1	1
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.006	0.095	-9999	-0.33	29	29
BIRC5	-0.14	0.25	-9999	-0.55	137	137
NFKBIA	0.029	0.049	-9999	-10000	0	0
CPEB1	-0.002	0.099	-9999	-0.59	14	14
AKT1	0.029	0.049	-9999	-0.28	2	2
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	0.002	0.052	-9999	-0.39	3	3
NDEL1/TACC3	-0.012	0.092	-9999	-0.37	20	20
GADD45A	-0.017	0.12	-9999	-0.49	32	32
GSK3B	0.017	0.03	-9999	-0.6	1	1
PAK1/Aurora A	-0.006	0.1	-9999	-0.3	38	38
MDM2	0.012	0.031	-9999	-0.49	2	2
JUB	-0.013	0.12	-9999	-0.57	24	24
TPX2	-0.038	0.15	-9999	-0.38	81	81
TP53	0.021	0.063	-9999	-0.3	11	11
DLG7	0.018	0.049	-9999	-0.29	2	2
AURKAIP1	0.013	0.022	-9999	-0.49	1	1
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.01	0.1	-9999	-0.39	20	20
G2/M transition of mitotic cell cycle	0.002	0.052	-9999	-0.39	3	3
AURKA	0.023	0.061	-9999	-0.34	2	2
AURKB	-0.083	0.13	-9999	-0.3	120	120
CDC25B	0.024	0.048	-9999	-0.27	2	2
G2/M transition checkpoint	-0.011	0.074	-9999	-0.29	23	23
mRNA polyadenylation	-0.005	0.073	-9999	-0.37	14	14
Aurora A/CPEB	-0.005	0.074	-9999	-0.37	14	14
Aurora A/TACC1/TRAP/chTOG	0.011	0.047	-9999	-10000	0	0
BRCA1	0.01	0.044	-9999	-0.49	4	4
centrosome duplication	-0.005	0.1	-9999	-0.3	38	38
regulation of centrosome cycle	-0.023	0.084	-9999	-0.36	20	20
spindle assembly	0.005	0.043	-9999	-10000	0	0
TDRD7	0.012	0.038	-9999	-0.59	2	2
Aurora A/RasGAP/Survivin	-0.071	0.12	-9999	-0.36	28	28
CENPA	-0.057	0.13	-9999	-0.32	77	77
Aurora A/PP2A	0.025	0.047	-9999	-0.28	2	2
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.032	0.046	-9999	-0.26	2	2
negative regulation of DNA binding	0.021	0.062	-9999	-0.3	11	11
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.011	0.074	-9999	-0.29	23	23
mitotic prometaphase	0.022	0.037	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.061	-9999	-0.34	2	2
TACC1	0.014	0	-9999	-10000	0	0
TACC3	-0.026	0.14	-9999	-0.5	40	40
Aurora A/Antizyme1	0.032	0.044	-9999	-10000	0	0
Aurora A/RasGAP	0.025	0.047	-9999	-0.28	2	2
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.014	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.028	0.085	-9999	-0.29	49	49
Importin alpha/Importin beta/TPX2	-0.038	0.15	-9999	-0.38	81	81
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	-0.015	0.13	-9999	-0.36	43	43
PAK1	-0.035	0.15	-9999	-0.5	49	49
CKAP5	0.014	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.021	0.088	-9999	-0.37	29	29
alphaV beta3 Integrin	-0.04	0.11	-9999	-0.39	16	16
PTK2	-0.012	0.14	-9999	-0.46	21	21
IGF1R	0.013	0.022	-9999	-0.49	1	1
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.01	0.051	-9999	-0.57	4	4
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.028	0.089	-9999	-0.49	15	15
VEGFA	-0.007	0.1	-9999	-0.49	22	22
ILK	-0.028	0.089	-9999	-0.49	15	15
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	0.009	0.092	-9999	-0.45	15	15
PTK2B	-0.021	0.14	-9999	-0.5	20	20
alphaV/beta3 Integrin/JAM-A	-0.012	0.13	-9999	-0.53	9	9
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.039	0.1	-9999	-0.36	14	14
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.012	0.058	-9999	-0.32	14	14
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.011	0.085	-9999	-0.37	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.064	0.14	-9999	-0.45	40	40
PI4KA	0.005	0.066	-9999	-0.49	9	9
IGF-1R heterotetramer/IGF1/IRS1	-0.045	0.11	-9999	-0.47	19	19
PI4 Kinase	-0.006	0.045	-9999	-0.34	9	9
PIK3CA	0.013	0.027	-9999	-0.59	1	1
alphaV/beta3 Integrin/Osteopontin	-0.094	0.16	-9999	-0.36	134	134
RPS6KB1	0.009	0.12	-9999	-0.44	19	19
TLN1	0.014	0	-9999	-10000	0	0
MAPK3	0.006	0.12	-9999	-0.45	19	19
GPR124	0.01	0.044	-9999	-0.49	4	4
MAPK1	0.006	0.12	-9999	-0.45	20	20
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.085	0.16	-9999	-0.34	127	127
cell adhesion	-0.033	0.085	-9999	-0.34	14	14
ANGPTL3	0.006	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.017	0.073	-9999	-0.44	5	5
IGF-1R heterotetramer	0.013	0.022	-9999	-0.49	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.009	0.05	-9999	-0.49	5	5
ITGB3	-0.052	0.18	-9999	-0.51	65	65
IGF1	-0.008	0.11	-9999	-0.56	20	20
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.04	0.1	-9999	-0.38	16	16
apoptosis	0.013	0.027	-9999	-0.59	1	1
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.038	0.1	-9999	-0.36	14	14
VCL	0.008	0.058	-9999	-0.52	6	6
alphaV/beta3 Integrin/Del1	-0.085	0.16	-9999	-0.42	64	64
CSF1	-0.006	0.11	-9999	-0.59	17	17
PIK3C2A	-0.031	0.097	-9999	-0.5	17	17
PI4 Kinase/Pyk2	-0.057	0.12	-9999	-0.43	32	32
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.12	-9999	-0.43	35	35
FAK1/Vinculin	-0.003	0.13	-9999	-0.41	16	16
alphaV beta3/Integrin/ppsTEM5	-0.04	0.1	-9999	-0.38	16	16
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.007	0.11	-9999	-0.56	19	19
BCAR1	0.013	0.027	-9999	-0.59	1	1
FGF2	0.011	0.044	-9999	-0.56	3	3
F11R	0.014	0.065	-9999	-0.36	15	15
alphaV/beta3 Integrin/Lactadherin	-0.041	0.1	-9999	-0.36	17	17
alphaV/beta3 Integrin/TGFBR2	-0.041	0.11	-9999	-0.39	17	17
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.012	0.06	-9999	-0.32	19	19
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.034	0.09	-9999	-0.32	14	14
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.004	0.093	-9999	-0.49	18	18
alphaV/beta3 Integrin/Pyk2	-0.02	0.14	-9999	-0.5	20	20
SDC1	-0.032	0.15	-9999	-0.51	45	45
VAV3	-0.039	0.14	-9999	-0.55	6	6
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	-0.001	0.12	-9999	-0.39	13	13
cell migration	0.007	0.12	-9999	-0.41	9	9
ITGAV	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.042	0.097	-9999	-0.47	9	9
SPP1	-0.084	0.21	-9999	-0.54	91	91
KDR	0.005	0.071	-9999	-0.52	9	9
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.013	0.027	-9999	-0.59	1	1
COL4A3	-0.069	0.2	-9999	-0.52	80	80
angiogenesis	0.008	0.13	-9999	-0.46	20	20
Rac1/GTP	-0.062	0.11	-9999	-0.5	6	6
EDIL3	-0.067	0.2	-9999	-0.57	71	71
cell proliferation	-0.041	0.11	-9999	-0.39	17	17

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.001	0.095	-9999	-0.59	13	13
Caspase 8 (4 units)	-0.011	0.082	-9999	-0.36	15	15
NEF	-0.004	0.031	-9999	-10000	0	0
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	0	0.16	-9999	-0.54	43	43
CYCS	0.023	0.084	-9999	-0.32	12	12
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.024	0.15	-9999	-0.6	31	31
MAP2K7	0.017	0.075	-9999	-0.32	2	2
protein ubiquitination	0.017	0.093	-9999	-0.4	7	7
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	-0.005	0.1	-9999	-0.54	18	18
BID	0.016	0.088	-9999	-0.35	12	12
NF-kappa-B/RelA/I kappa B alpha	-0.021	0.071	-9999	-10000	0	0
TRADD	0.013	0.027	-9999	-0.59	1	1
MAP3K5	0.006	0.07	-9999	-0.59	7	7
CFLAR	0.013	0.022	-9999	-0.49	1	1
FADD	0.014	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.021	0.072	-9999	-10000	0	0
MAPK8	0.017	0.085	-9999	-0.51	1	1
APAF1	0.014	0	-9999	-10000	0	0
TRAF1	0.004	0.078	-9999	-0.58	9	9
TRAF2	0.014	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.091	-9999	-0.36	14	14
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.001	0.11	-9999	-0.53	8	8
CHUK	0.016	0.099	-9999	-0.44	7	7
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.02	0.072	-9999	-0.47	2	2
TCRz/NEF	-0.038	0.13	-9999	-0.42	47	47
TNF	-0.15	0.26	-9999	-0.54	156	156
FASLG	-0.027	0.17	-9999	-0.56	42	42
NFKB1	0.009	0.029	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.11	0.17	-9999	-0.34	171	171
CASP6	-0.019	0.067	-9999	-0.58	3	3
CASP7	0.031	0.16	-9999	-0.51	33	33
RELA	0.009	0.029	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.031	0.16	-9999	-0.51	33	33
TNFRSF1A	0.001	0.086	-9999	-0.55	12	12
TNFR1A/BAG4	-0.02	0.093	-9999	-0.44	23	23
CASP8	-0.002	0.089	-9999	-0.5	16	16
CASP9	0.013	0.022	-9999	-0.49	1	1
MAP3K14	0.008	0.11	-9999	-0.48	8	8
APAF-1/Caspase 9	-0.038	0.11	-9999	-0.4	35	35
BCL2	0.02	0.088	-9999	-0.48	2	2

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.034	0.093	0.18	3	-0.4	18	21
CaM/Ca2+	-0.002	0.025	-10000	0	-0.4	2	2
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.013	0.027	-10000	0	-0.59	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.027	0.14	0.25	64	-0.4	21	85
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.012	0.035	-10000	0	-0.54	2	2
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	-0.009	0.11	-10000	0	-0.49	24	24
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.02	-10000	0	-0.32	2	2
YWHAG	0.001	0.079	-10000	0	-0.49	13	13
ASIP	-0.097	0.22	-10000	0	-0.55	100	100
PRKCI	0.014	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	-0.002	0.025	-10000	0	-0.4	2	2
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.034	0.014	-10000	0	-0.29	1	1
PRKCZ	-0.015	0.12	-10000	0	-0.55	26	26
TRIP10	0.007	0.065	-10000	0	-0.55	7	7
TC10/GTP/CIP4/Exocyst	-0.005	0.039	-10000	0	-0.33	7	7
AS160/14-3-3	0.003	0.087	-10000	0	-0.37	3	3
VAMP2	0.013	0.022	-10000	0	-0.49	1	1
SLC2A4	0.026	0.15	0.25	64	-0.45	21	85
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.028	0.016	-10000	0	-0.34	1	1
SFN	-0.11	0.23	-10000	0	-0.53	117	117
LNPEP	-0.012	0.12	-10000	0	-0.59	22	22
YWHAE	0.014	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.014	0.12	-10000	0	-0.54	26	26
positive regulation of NF-kappaB transcription factor activity	-0.03	0.1	-10000	0	-0.37	41	41
MAP2K4	0.029	0.064	-10000	0	-0.35	3	3
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0.051	-10000	0	-0.57	4	4
TNFRSF10A	-0.026	0.15	-10000	0	-0.56	36	36
SMPD1	0.01	0.048	-10000	0	-0.23	14	14
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.001	0.087	-10000	0	-0.5	15	15
TRAIL/TRAILR2	-0.022	0.094	-10000	0	-0.4	29	29
TRAIL/TRAILR3	-0.042	0.13	-10000	0	-0.41	53	53
TRAIL/TRAILR1	-0.047	0.13	-10000	0	-0.41	59	59
TRAIL/TRAILR4	-0.03	0.1	-10000	0	-0.37	41	41
TRAIL/TRAILR1/DAP3/GTP	-0.036	0.1	-10000	0	-0.31	59	59
IKK complex	-0.01	0.03	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.004	0.089	-10000	0	-0.38	26	26
MAP3K1	0.023	0.064	-10000	0	-0.34	2	2
TRAILR4 (trimer)	-0.001	0.087	-10000	0	-0.5	15	15
TRADD	0.013	0.027	-10000	0	-0.59	1	1
TRAILR1 (trimer)	-0.026	0.15	-10000	0	-0.56	36	36
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.012	0.082	-10000	0	-0.28	3	3
CFLAR	0.013	0.022	-10000	0	-0.49	1	1
MAPK1	0.004	0.089	-10000	0	-0.38	26	26
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.032	0.091	-10000	0	-0.47	3	3
mol:ceramide	0.01	0.048	-10000	0	-0.23	14	14
FADD	0.014	0	-10000	0	-10000	0	0
MAPK8	0.029	0.082	-10000	0	-0.36	8	8
TRAF2	0.014	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.02	0.13	-10000	0	-0.53	32	32
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.039	0.11	-10000	0	-0.34	59	59
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.022	0.087	0.27	1	-0.38	15	16
JNK cascade	-0.03	0.1	-10000	0	-0.37	41	41
TRAIL (trimer)	-0.014	0.12	-10000	0	-0.54	26	26
TNFRSF10C	-0.02	0.13	-10000	0	-0.53	32	32
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.033	0.092	-10000	0	-0.31	39	39
TRAIL/TRAILR2/FADD	-0.019	0.078	-10000	0	-0.38	14	14
cell death	0.01	0.048	-10000	0	-0.22	14	14
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.059	-10000	0	-0.52	1	1
TRAILR2 (trimer)	0.01	0.051	-10000	0	-0.56	4	4
CASP8	-0.003	0.05	-10000	0	-0.8	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.016	0.065	-10000	0	-0.6	1	1

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.066	0.14	-10000	0	-0.35	98	98
cell-cell adhesion	0.035	0.099	0.47	14	-10000	0	14
Ephrin B/EPHB2/RasGAP	-0.022	0.081	-10000	0	-0.36	18	18
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
SHC1	0.009	0.05	-10000	0	-0.49	5	5
Ephrin B1/EPHB3	-0.003	0.028	-10000	0	-0.29	5	5
Ephrin B1/EPHB1	-0.031	0.1	-10000	0	-0.37	43	43
HRAS/GDP	-0.031	0.094	-10000	0	-0.47	12	12
Ephrin B/EPHB1/GRB7	-0.058	0.14	-10000	0	-0.6	18	18
Endophilin/SYNJ1	0.016	0.089	-10000	0	-0.34	19	19
KRAS	0.013	0.022	-10000	0	-0.49	1	1
Ephrin B/EPHB1/Src	-0.039	0.11	-10000	0	-0.57	11	11
endothelial cell migration	-0.006	0.039	-10000	0	-0.29	4	4
GRB2	0.013	0.022	-10000	0	-0.49	1	1
GRB7	-0.031	0.14	-10000	0	-0.49	42	42
PAK1	-0.008	0.13	-10000	0	-0.47	20	20
HRAS	0.014	0	-10000	0	-10000	0	0
RRAS	0.016	0.09	-10000	0	-0.35	19	19
DNM1	-0.1	0.22	-10000	0	-0.52	109	109
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.001	0.12	-10000	0	-0.54	11	11
lamellipodium assembly	-0.035	0.099	-10000	0	-0.47	14	14
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.11	-10000	0	-0.5	12	12
PIK3R1	0.014	0	-10000	0	-10000	0	0
EPHB2	0	0.087	-10000	0	-0.52	14	14
EPHB3	0.012	0.031	-10000	0	-0.49	2	2
EPHB1	-0.034	0.16	-10000	0	-0.59	41	41
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.091	-10000	0	-0.43	15	15
Ephrin B/EPHB2	-0.023	0.083	-10000	0	-0.37	18	18
Ephrin B/EPHB3	-0.017	0.068	-10000	0	-0.33	14	14
JNK cascade	0.006	0.11	-10000	0	-0.61	5	5
Ephrin B/EPHB1	-0.04	0.12	-10000	0	-0.36	50	50
RAP1/GDP	-0.026	0.078	-10000	0	-0.4	10	10
EFNB2	0.002	0.08	-10000	0	-0.52	12	12
EFNB3	-0.004	0.1	-10000	0	-0.56	16	16
EFNB1	0.011	0.038	-10000	0	-0.49	3	3
Ephrin B2/EPHB1-2	-0.04	0.12	-10000	0	-0.34	60	60
RAP1B	0.013	0.022	-10000	0	-0.49	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.037	0.11	-10000	0	-0.51	14	14
Rap1/GTP	-0.035	0.099	-10000	0	-0.48	14	14
axon guidance	-0.066	0.14	-10000	0	-0.34	98	98
MAPK3	0.023	0.1	-10000	0	-0.43	13	13
MAPK1	0.023	0.1	-10000	0	-0.43	13	13
Rac1/GDP	0.02	0.099	-10000	0	-0.39	14	14
actin cytoskeleton reorganization	-0.027	0.076	-10000	0	-0.38	12	12
CDC42/GDP	0.02	0.099	-10000	0	-0.42	11	11
PI3K	-0.006	0.039	-10000	0	-0.3	4	4
EFNA5	-0.084	0.21	-10000	0	-0.54	90	90
Ephrin B2/EPHB4	-0.007	0.047	-10000	0	-0.31	12	12
Ephrin B/EPHB2/Intersectin/N-WASP	0.022	0.07	-10000	0	-0.41	5	5
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.034	0.096	-10000	0	-0.46	14	14
PTK2	0.009	0.026	-10000	0	-10000	0	0
MAP4K4	0.006	0.11	-10000	0	-0.62	5	5
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.003	0.093	-10000	0	-0.5	17	17
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.12	-10000	0	-0.42	9	9
MAP2K1	0.015	0.11	-10000	0	-0.46	13	13
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.035	0.1	-10000	0	-0.35	44	44
cell migration	0.018	0.12	-10000	0	-0.48	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	0.016	0.09	-10000	0	-0.35	19	19
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.012	0.14	-10000	0	-0.54	15	15
HRAS/GTP	-0.038	0.11	-10000	0	-0.51	14	14
Ephrin B1/EPHB1-2	-0.035	0.11	-10000	0	-0.34	53	53
cell adhesion mediated by integrin	0.011	0.068	0.3	17	-10000	0	17
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.041	0.12	-10000	0	-0.55	14	14
RAC1-CDC42/GTP	-0.035	0.1	-10000	0	-0.48	15	15
RASA1	0.014	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.026	0.077	-10000	0	-0.4	11	11
ruffle organization	0.023	0.12	-10000	0	-0.48	14	14
NCK1	0.013	0.027	-10000	0	-0.59	1	1
receptor internalization	-0.032	0.14	-10000	0	-0.58	11	11
Ephrin B/EPHB2/KALRN	-0.03	0.09	-10000	0	-0.52	6	6
ROCK1	0.025	0.027	-10000	0	-0.25	5	5
RAS family/GDP	-0.025	0.072	-10000	0	-0.42	7	7
Rac1/GTP	-0.037	0.1	-10000	0	-0.51	14	14
Ephrin B/EPHB1/Src/Paxillin	0.005	0.11	-10000	0	-0.47	11	11

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.38	-9999	-1.1	60	60
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.067	0.18	-9999	-0.42	100	100
IFNAR2	0.013	0.006	-9999	-10000	0	0
AKT1	0.001	0.049	-9999	-0.23	12	12
ER alpha/Oestrogen	-0.011	0.089	-9999	-0.39	26	26
NFX1/SIN3/HDAC complex	0.04	0.032	-9999	-10000	0	0
EGF	-0.051	0.18	-9999	-0.56	58	58
SMG5	0.013	0.022	-9999	-0.49	1	1
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.019	0.012	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.34	-9999	-1	59	59
SAP18	0.013	0.004	-9999	-10000	0	0
MRN complex	-0.001	0.016	-9999	-0.36	1	1
WT1	-0.037	0.14	-9999	-0.49	44	44
WRN	0.009	0.053	-9999	-0.59	4	4
SP1	0.013	0.009	-9999	-10000	0	0
SP3	0.012	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.13	0.29	-9999	-0.9	58	58
Mad/Max	0.019	0.009	-9999	-10000	0	0
TERT	-0.14	0.4	-9999	-1.2	60	60
CCND1	-0.12	0.36	-9999	-1	67	67
MAX	0.012	0.006	-9999	-10000	0	0
RBBP7	0.013	0.004	-9999	-10000	0	0
RBBP4	0.012	0.027	-9999	-0.6	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.004	-9999	-10000	0	0
Telomerase/911	0.032	0.039	-9999	-10000	0	0
CDKN1B	0.011	0.077	-9999	-0.54	2	2
RAD1	0.014	0	-9999	-10000	0	0
XRCC5	0.014	0	-9999	-10000	0	0
XRCC6	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.027	-9999	-0.59	1	1
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.012	0.005	-9999	-10000	0	0
JUN	0.002	0.075	-9999	-0.5	11	11
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.007	-9999	-10000	0	0
FOS	-0.096	0.22	-9999	-0.55	99	99
IFN-gamma/IRF1	-0.011	0.088	-9999	-0.35	30	30
PARP2	0.014	0	-9999	-10000	0	0
BLM	-0.053	0.18	-9999	-0.53	63	63
Telomerase	-0.037	0.1	-9999	-0.4	29	29
IRF1	-0.009	0.11	-9999	-0.48	27	27
ESR1	-0.015	0.12	-9999	-0.54	26	26
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0.022	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.045	0.033	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.045	0.034	-9999	-10000	0	0
HDAC1	0.008	0.053	-9999	-0.59	4	4
HDAC2	0.012	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.019	0.059	-9999	-0.42	9	9
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.012	0.006	-9999	-10000	0	0
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.013	0.022	-9999	-0.49	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.33	-9999	-1	58	58
NR2F2	-0.009	0.12	-9999	-0.51	25	25
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.004	0.079	-9999	-0.59	9	9
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.014	0	-9999	-10000	0	0
EGFR	-0.084	0.21	-9999	-0.55	89	89
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.097	0.2	-9999	-0.43	132	132
MYC	-0.016	0.13	-9999	-0.58	25	25
IL2	-0.003	0.014	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0.027	-9999	-0.59	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
TGFB1	0.004	0.079	-9999	-0.59	9	9
TRF2/BLM	-0.043	0.12	-9999	-0.35	63	63
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.35	-9999	-1	58	58
SP1/HDAC2	0.019	0.017	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.13	0.29	-9999	-0.9	58	58
Smad3/Myc	0.006	0.096	-9999	-0.36	33	33
911 complex	-0.001	0.012	-9999	-0.28	1	1
IFNG	0.003	0.049	-9999	-0.49	5	5
Telomerase/PinX1	-0.13	0.29	-9999	-0.9	58	58
Telomerase/AKT1/mTOR/p70S6K	0.009	0.074	-9999	-10000	0	0
SIN3B	0.013	0.004	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.13	0.29	-9999	-0.91	58	58
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.001	0.012	-9999	-10000	0	0
TRF2/WRN	-0.003	0.035	-9999	-0.4	4	4
Telomerase/hnRNP C1/C2	-0.13	0.29	-9999	-0.9	58	58
E2F1	-0.016	0.12	-9999	-0.52	28	28
ZNFX1	0.013	0.004	-9999	-10000	0	0
PIF1	-0.051	0.18	-9999	-0.54	60	60
NCL	0.014	0	-9999	-10000	0	0
DKC1	0.014	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.019	0.066	-10000	0	-0.38	2	2
adherens junction organization	-0.03	0.12	-10000	0	-0.37	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.02	0.12	-10000	0	-0.42	8	8
FMN1	-0.061	0.15	-10000	0	-0.5	24	24
mol:IP3	0.01	0.067	-10000	0	-0.4	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.11	-10000	0	-0.27	66	66
CTNNB1	0.016	0.004	-10000	0	-10000	0	0
AKT1	0.012	0.076	-10000	0	-0.43	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.031	0.15	-10000	0	-0.41	61	61
CTNND1	0.014	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.007	0.1	-10000	0	-0.5	3	3
VASP	-0.008	0.1	-10000	0	-0.52	3	3
ZYX	-0.011	0.11	-10000	0	-0.5	4	4
JUB	-0.021	0.12	-10000	0	-0.51	9	9
EGFR(dimer)	-0.056	0.15	-10000	0	-0.43	26	26
E-cadherin/beta catenin-gamma catenin	-0.083	0.14	-10000	0	-0.32	134	134
mol:PI-3-4-5-P3	-0.03	0.061	-10000	0	-0.4	3	3
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.031	0.062	-10000	0	-0.41	3	3
FYN	0.02	0.066	-10000	0	-10000	0	0
mol:Ca2+	0.01	0.066	-10000	0	-0.39	2	2
JUP	0.005	0.081	-10000	0	-0.57	10	10
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	0.01	0.067	-10000	0	-0.4	2	2
CDH1	-0.12	0.24	-10000	0	-0.54	127	127
RhoA/GDP	-0.02	0.12	-10000	0	-0.38	12	12
establishment of polarity of embryonic epithelium	-0.007	0.1	-10000	0	-0.5	3	3
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.083	0.21	-10000	0	-0.55	89	89
CASR	0.008	0.074	-10000	0	-0.36	2	2
RhoA/GTP	-0.02	0.042	-10000	0	-0.35	2	2
AKT2	0.012	0.076	-10000	0	-0.43	2	2
actin cable formation	-0.052	0.15	-10000	0	-0.48	25	25
apoptosis	0.026	0.054	0.42	2	-10000	0	2
CTNNA1	0.014	0.002	-10000	0	-10000	0	0
mol:GDP	-0.03	0.12	-10000	0	-0.4	17	17
PIP5K1A	-0.007	0.1	-10000	0	-0.52	3	3
PLCG1	0.01	0.068	-10000	0	-0.4	2	2
Rac1/GTP	-0.077	0.12	-10000	0	-0.39	26	26
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.007	0.091	-9999	-0.32	37	37
SNTA1	-0.027	0.15	-9999	-0.57	36	36
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.006	0.094	-9999	-0.32	39	39
MAPK12	0.026	0.044	-9999	-0.35	5	5
CCND1	0.007	0.072	-9999	-0.41	12	12
p38 gamma/SNTA1	0.01	0.09	-9999	-0.3	34	34
MAP2K3	0.011	0.038	-9999	-0.49	3	3
PKN1	0.014	0	-9999	-10000	0	0
G2/M transition checkpoint	0.026	0.044	-9999	-0.34	5	5
MAP2K6	0.022	0.032	-9999	-0.32	2	2
MAPT	0.011	0.085	-9999	-0.31	25	25
MAPK13	-0.005	0.11	-9999	-0.38	37	37
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.031	-9999	-0.35	1	1

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.025	0.099	-10000	0	-0.42	30	30
ATM	0.014	0	-10000	0	-10000	0	0
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.015	0.057	-10000	0	-0.34	6	6
protein ubiquitination	-0.026	0.092	-10000	0	-0.58	5	5
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	-0.001	0.016	-10000	0	-0.36	1	1
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.014	0.055	-10000	0	-0.38	7	7
FANCF	0.014	0	-10000	0	-10000	0	0
BRCA1	0.01	0.044	-10000	0	-0.49	4	4
CCNE1	0.011	0.038	-10000	0	-0.49	3	3
CDK2/Cyclin E1	-0.011	0.067	-10000	0	-0.39	15	15
FANCG	0.013	0.022	-10000	0	-0.49	1	1
BRCA1/BACH1/BARD1	-0.027	0.1	-10000	0	-0.42	33	33
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.011	0.041	-10000	0	-0.52	3	3
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	-0.027	0.14	-10000	0	-0.51	40	40
DNA repair	0.017	0.15	-10000	0	-0.51	16	16
BRCA1/BARD1/ubiquitin	-0.027	0.1	-10000	0	-0.42	33	33
BARD1/DNA-PK	-0.018	0.073	-10000	0	-0.32	28	28
FANCL	0.014	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.025	0.099	0.42	30	-10000	0	30
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.075	-10000	0	-0.47	3	3
BRCA1/BACH1/BARD1/TopBP1	-0.023	0.091	-10000	0	-0.36	33	33
BRCA1/BARD1/P53	-0.029	0.096	-10000	0	-0.34	41	41
BARD1/CSTF1/BRCA1	-0.023	0.087	-10000	0	-0.36	29	29
BRCA1/BACH1	0.01	0.044	-10000	0	-0.49	4	4
BARD1	-0.021	0.14	-10000	0	-0.58	30	30
PCNA	0.012	0.031	-10000	0	-0.49	2	2
BRCA1/BARD1/UbcH5C	-0.023	0.087	-10000	0	-0.35	33	33
BRCA1/BARD1/UbcH7	-0.023	0.087	-10000	0	-0.35	33	33
BRCA1/BARD1/RAD51/PCNA	-0.052	0.12	-10000	0	-0.38	44	44
BARD1/DNA-PK/P53	-0.025	0.085	-10000	0	-0.6	2	2
BRCA1/BARD1/Ubiquitin	-0.027	0.1	-10000	0	-0.42	33	33
BRCA1/BARD1/CTIP	0.012	0.093	-10000	0	-0.34	29	29
FA complex	0.028	0.057	-10000	0	-10000	0	0
BARD1/EWS	-0.025	0.099	-10000	0	-0.42	30	30
RBBP8	0.023	0.028	-10000	0	-0.34	3	3
TP53	-0.003	0.1	-10000	0	-0.58	15	15
TOPBP1	0.013	0.027	-10000	0	-0.59	1	1
G1/S transition of mitotic cell cycle	0.029	0.095	0.33	41	-10000	0	41
BRCA1/BARD1	-0.026	0.094	-10000	0	-0.59	5	5
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.025	0.1	-10000	0	-0.43	30	30
CDK2	0	0.086	-10000	0	-0.53	13	13
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.049	0.17	-10000	0	-0.51	61	61
RAD50	0.013	0.027	-10000	0	-0.59	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.027	0.1	-10000	0	-0.42	33	33
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.013	0.027	-9999	-0.59	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.012	0.031	-9999	-0.49	2	2
RAC1-CDC42/GTP/PAK family	-0.032	0.1	-9999	-0.22	107	107
response to UV	0	0	-9999	-10000	0	0
YES1	0.009	0.053	-9999	-0.59	4	4
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
MAP3K12	0.014	0	-9999	-10000	0	0
FGR	0.011	0.038	-9999	-0.49	3	3
p38 alpha/TAB1	-0.026	0.057	-9999	-0.32	8	8
PRKG1	-0.039	0.17	-9999	-0.58	46	46
DUSP8	0	0.086	-9999	-0.53	13	13
PGK/cGMP/p38 alpha	-0.044	0.09	-9999	-0.3	37	37
apoptosis	-0.025	0.055	-9999	-0.31	8	8
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.004	0.073	-9999	-0.51	10	10
DUSP1	-0.02	0.13	-9999	-0.53	32	32
PAK1	-0.035	0.15	-9999	-0.5	49	49
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.021	-9999	-10000	0	0
TRAF6	0.013	0.027	-9999	-0.59	1	1
RAC1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0.022	-9999	-0.49	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.005	0.1	-9999	-0.41	10	10
BLK	-0.11	0.22	-9999	-0.52	114	114
HCK	-0.007	0.11	-9999	-0.54	20	20
MAP2K3	0.011	0.038	-9999	-0.49	3	3
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	-0.004	0.1	-9999	-0.55	17	17
TRAF6/MEKK3	-0.001	0.015	-9999	-0.33	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.007	0.081	-9999	-0.36	7	7
positive regulation of innate immune response	0	0.11	-9999	-0.43	10	10
LCK	-0.081	0.21	-9999	-0.54	89	89
p38alpha-beta/MKP7	0.007	0.1	-9999	-0.43	8	8
p38alpha-beta/MKP5	-0.001	0.12	-9999	-0.43	12	12
PGK/cGMP	-0.038	0.12	-9999	-0.42	46	46
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.008	0.12	-9999	-0.42	13	13
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.12	0.24	-9999	-0.56	116	116

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.025	0.081	-10000	0	-0.31	30	30
ER alpha/Gai/GDP/Gbeta gamma	0.026	0.088	-10000	0	-0.38	16	16
AKT1	0.017	0.12	-10000	0	-0.72	13	13
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.015	0.12	-10000	0	-0.73	13	13
mol:Ca2+	-0.008	0.14	-10000	0	-0.5	24	24
IGF1R	0.013	0.022	-10000	0	-0.49	1	1
E2/ER alpha (dimer)/Striatin	-0.035	0.11	-10000	0	-0.35	52	52
SHC1	0.009	0.05	-10000	0	-0.49	5	5
apoptosis	-0.017	0.12	0.69	13	-10000	0	13
RhoA/GTP	-0.011	0.049	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.02	0.074	-10000	0	-0.39	16	16
regulation of stress fiber formation	-0.015	0.099	0.4	9	-10000	0	9
E2/ERA-ERB (dimer)	-0.028	0.096	-10000	0	-0.35	41	41
KRAS	0.013	0.022	-10000	0	-0.49	1	1
G13/GTP	-0.015	0.065	-10000	0	-0.29	26	26
pseudopodium formation	0.015	0.099	-10000	0	-0.4	9	9
E2/ER alpha (dimer)/PELP1	-0.016	0.072	-10000	0	-0.32	26	26
GRB2	0.013	0.022	-10000	0	-0.49	1	1
GNG2	0.009	0.053	-10000	0	-0.59	4	4
GNAO1	0.008	0.06	-10000	0	-0.59	5	5
HRAS	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.027	0.096	-10000	0	-0.45	12	12
E2/ER beta (dimer)	-0.014	0.074	-10000	0	-0.41	17	17
mol:GDP	-0.023	0.082	-10000	0	-0.36	26	26
mol:NADP	0.027	0.096	-10000	0	-0.45	12	12
PIK3R1	0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.01	0.14	-10000	0	-0.52	24	24
IGF-1R heterotetramer	0.013	0.022	-10000	0	-0.49	1	1
PLCB1	-0.007	0.13	-10000	0	-0.48	21	21
PLCB2	-0.007	0.14	-10000	0	-0.53	23	23
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
mol:L-citrulline	0.027	0.096	-10000	0	-0.45	12	12
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.013	0.078	-10000	0	-0.7	5	5
JNK cascade	-0.014	0.074	-10000	0	-0.41	17	17
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
ESR2	-0.005	0.1	-10000	0	-0.56	17	17
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.014	0.12	-10000	0	-0.54	26	26
Gq family/GDP/Gbeta gamma	0.01	0.12	-10000	0	-0.45	24	24
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.032	0.054	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.021	0.078	-10000	0	-0.4	17	17
GNAZ	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.02	0.086	-10000	0	-0.39	26	26
STRN	-0.017	0.13	-10000	0	-0.59	27	27
GNAL	-0.055	0.19	-10000	0	-0.59	59	59
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.002	0.082	-10000	0	-0.35	26	26
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.1	-10000	0	-0.59	16	16
HBEGF	-0.004	0.12	-10000	0	-0.48	8	8
cAMP biosynthetic process	-0.055	0.12	-10000	0	-0.31	82	82
SRC	0.033	0.084	-10000	0	-0.35	16	16
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.021	0.073	-10000	0	-0.34	14	14
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.074	-10000	0	-0.34	16	16
Gs family/GTP	-0.056	0.12	-10000	0	-0.32	81	81
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0.011	-10000	0	-0.25	1	1
vasodilation	0.027	0.092	-10000	0	-0.43	12	12
mol:DAG	-0.01	0.14	-10000	0	-0.52	24	24
Gs family/GDP/Gbeta gamma	-0.045	0.1	-10000	0	-0.37	20	20
MSN	0.014	0.11	-10000	0	-0.43	9	9
Gq family/GTP	-0.005	0.12	-10000	0	-0.5	19	19
mol:PI-3-4-5-P3	0.016	0.12	-10000	0	-0.7	13	13
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.027	0.092	0.43	12	-10000	0	12
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
RhoA/GDP	-0.021	0.076	-10000	0	-0.33	26	26
NOS3	0.027	0.099	-10000	0	-0.47	12	12
GNA11	0.004	0.08	-10000	0	-0.59	9	9
MAPKKK cascade	0.022	0.13	-10000	0	-0.52	16	16
E2/ER alpha (dimer)/PELP1/Src	-0.021	0.076	-10000	0	-0.4	16	16
ruffle organization	0.015	0.099	-10000	0	-0.4	9	9
ROCK2	0.027	0.083	-10000	0	-0.51	2	2
GNA14	-0.014	0.12	-10000	0	-0.56	25	25
GNA15	-0.007	0.11	-10000	0	-0.56	19	19
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.033	0.14	-10000	0	-0.45	15	15
MMP2	0.027	0.1	-10000	0	-0.48	6	6

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.1	0.23	-9999	-0.55	103	103
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0	-9999	-10000	0	0
TCEB1	0.014	0	-9999	-10000	0	0
HIF1A/p53	0.021	0.056	-9999	-0.27	14	14
HIF1A	0.023	0.025	-9999	-0.24	1	1
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.1	0.23	-9999	-0.56	104	104
ARNT/IPAS	-0.08	0.16	-9999	-0.39	104	104
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.03	0.028	-9999	-0.3	1	1
CUL2	0.014	0	-9999	-10000	0	0
OS9	0.003	0.073	-9999	-0.49	11	11
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.03	0.024	-9999	-10000	0	0
PHD1-3/OS9	-0.013	0.06	-9999	-0.32	13	13
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.014	-9999	-10000	0	0
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.03	0.024	-9999	-0.22	1	1
EGLN3	-0.001	0.095	-9999	-0.59	13	13
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	-0.003	0.1	-9999	-0.58	15	15
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.041	0.006	-9999	-10000	0	0
ARNT	0.013	0.022	-9999	-0.49	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.028	0.12	-9999	-0.28	85	85

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.021	0.04	-9999	-0.43	4	4
SMARCC1	0.01	0.013	-9999	-10000	0	0
REL	-0.017	0.13	-9999	-0.56	29	29
HDAC7	0.021	0.1	-9999	-0.4	7	7
JUN	0.002	0.074	-9999	-0.5	11	11
EP300	0.009	0.053	-9999	-0.59	4	4
KAT2B	0.013	0.022	-9999	-0.49	1	1
KAT5	0.014	0	-9999	-10000	0	0
MAPK14	0.023	0.023	-9999	-0.42	1	1
FOXO1	0.011	0.044	-9999	-0.56	3	3
T-DHT/AR	0.017	0.11	-9999	-0.43	7	7
MAP2K6	0.012	0.027	-9999	-0.59	1	1
BRM/BAF57	0.004	0.021	-9999	-0.43	1	1
MAP2K4	0.012	0.032	-9999	-0.5	2	2
SMARCA2	0.012	0.027	-9999	-0.59	1	1
PDE9A	-0.021	0.097	-9999	-1.2	2	2
NCOA2	-0.028	0.15	-9999	-0.59	35	35
CEBPA	-0.016	0.13	-9999	-0.56	27	27
EHMT2	0.013	0.004	-9999	-10000	0	0
cell proliferation	0.032	0.12	-9999	-0.46	9	9
NR0B1	-0.1	0.23	-9999	-0.55	103	103
EGR1	-0.11	0.23	-9999	-0.54	115	115
RXRs/9cRA	-0.035	0.11	-9999	-0.32	65	65
AR/RACK1/Src	-0.01	0.078	-9999	-0.39	9	9
AR/GR	-0.015	0.12	-9999	-0.4	16	16
GNB2L1	0.014	0.001	-9999	-10000	0	0
PKN1	0.014	0	-9999	-10000	0	0
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.011	0.075	-9999	-0.42	15	15
T-DHT/AR/TIF2/CARM1	-0.002	0.14	-9999	-0.54	21	21
SRC	0.029	0.062	-9999	-0.3	3	3
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.046	0.14	-9999	-0.5	11	11
APPBP2	0.014	0.005	-9999	-10000	0	0
TRIM24	0.012	0.023	-9999	-0.49	1	1
T-DHT/AR/TIP60	0.012	0.085	-9999	-0.44	7	7
TMPRSS2	-0.13	0.31	-9999	-1.1	44	44
RXRG	-0.061	0.2	-9999	-0.58	65	65
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.001	-9999	-10000	0	0
RXRB	0.014	0.001	-9999	-10000	0	0
CARM1	0.014	0.001	-9999	-10000	0	0
NR2C2	0.002	0.084	-9999	-0.59	10	10
KLK2	-0.008	0.15	-9999	-0.47	25	25
AR	-0.023	0.13	-9999	-0.3	71	71
SENP1	0.014	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.013	0.032	-9999	-0.49	2	2
SRY	-0.02	0.11	-9999	-0.49	26	26
GATA2	-0.004	0.1	-9999	-0.56	16	16
MYST2	0.014	0.001	-9999	-10000	0	0
HOXB13	-0.053	0.16	-9999	-0.5	60	60
T-DHT/AR/RACK1/Src	0.019	0.085	-9999	-0.42	7	7
positive regulation of transcription	-0.004	0.1	-9999	-0.56	16	16
DNAJA1	0.014	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.026	-9999	-0.24	4	4
NCOA1	0.017	0.005	-9999	-10000	0	0
SPDEF	-0.043	0.17	-9999	-0.54	52	52
T-DHT/AR/TIF2	0.015	0.12	-9999	-0.58	13	13
T-DHT/AR/Hsp90	0.012	0.085	-9999	-0.44	7	7
GSK3B	0.013	0.027	-9999	-0.59	1	1
NR2C1	0.014	0.001	-9999	-10000	0	0
mol:T-DHT	0.023	0.066	-9999	-0.31	15	15
SIRT1	0.014	0	-9999	-10000	0	0
ZMIZ2	0.015	0.005	-9999	-10000	0	0
POU2F1	0.025	0.014	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.049	0.15	-9999	-0.4	42	42
CREBBP	0.014	0	-9999	-10000	0	0
SMARCE1	0.013	0.003	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.017	0.13	-10000	0	-0.5	17	17
BAG4	-0.001	0.095	-10000	0	-0.59	13	13
BAD	0.008	0.045	-10000	0	-0.19	2	2
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.033	0.16	-10000	0	-0.55	43	43
BAX	0.008	0.045	-10000	0	-0.19	2	2
EnzymeConsortium:3.1.4.12	-0.003	0.033	-10000	0	-0.1	17	17
IKBKB	-0.008	0.12	-10000	0	-0.46	17	17
MAP2K2	0.018	0.049	-10000	0	-10000	0	0
MAP2K1	0.017	0.05	-10000	0	-0.3	1	1
SMPD1	0.003	0.033	-10000	0	-0.13	4	4
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.12	-10000	0	-0.46	18	18
MAP2K4	0.011	0.055	-10000	0	-0.28	3	3
protein ubiquitination	-0.006	0.12	-10000	0	-0.46	17	17
EnzymeConsortium:2.7.1.37	0.019	0.056	-10000	0	-0.29	1	1
response to UV	0	0.001	-10000	0	-0.002	3	3
RAF1	0.013	0.049	-10000	0	-0.2	2	2
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0	0.047	-10000	0	-0.15	17	17
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.053	-10000	0	-0.22	9	9
TRADD	0.013	0.027	-10000	0	-0.59	1	1
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.02	0.049	-10000	0	-10000	0	0
MAPK1	0.02	0.049	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	-0.016	0.13	-10000	0	-0.5	17	17
KSR1	0.007	0.047	-10000	0	-0.2	2	2
MAPK8	0.011	0.068	-10000	0	-0.26	16	16
TRAF2	0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.008	0.12	-10000	0	-0.46	17	17
TNF R/SODD	-0.018	0.094	-10000	0	-0.44	23	23
TNF	-0.15	0.26	-10000	0	-0.54	156	156
CYCS	0.011	0.044	0.14	4	-0.19	2	6
IKBKG	-0.008	0.12	-10000	0	-0.46	17	17
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.026	0.13	-10000	0	-0.53	17	17
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.011	0.044	0.14	4	-0.19	2	6
TNF/TNF R/SODD	-0.11	0.17	-10000	0	-0.34	171	171
TNFRSF1A	0.001	0.085	-10000	0	-0.55	12	12
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.051	-10000	0	-0.72	1	1
NSMAF	-0.016	0.12	-10000	0	-0.48	17	17
response to hydrogen peroxide	0	0.001	-10000	0	-0.002	3	3
BCL2	0.005	0.075	-10000	0	-0.59	8	8

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0.022	-10000	0	-0.49	1	1
Rac1/GDP	0.006	0.017	-10000	0	-10000	0	0
DOCK1	0.009	0.053	-10000	0	-0.59	4	4
ITGA4	-0.051	0.18	-10000	0	-0.53	61	61
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.076	0.17	-10000	0	-0.43	92	92
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.038	0.1	-10000	0	-0.37	27	27
alpha4/beta7 Integrin/Paxillin	-0.027	0.14	-10000	0	-0.36	56	56
lamellipodium assembly	0.004	0.038	-10000	0	-0.37	1	1
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PI3K	-0.001	0.019	-10000	0	-0.43	1	1
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.014	0	-10000	0	-10000	0	0
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
ARF6/GTP	-0.027	0.076	-10000	0	-0.43	2	2
cell adhesion	-0.03	0.084	-10000	0	-0.46	2	2
CRKL/CBL	-0.001	0.015	-10000	0	-0.34	1	1
alpha4/beta1 Integrin/Paxillin	-0.002	0.1	-10000	0	-0.33	27	27
ITGB1	0.012	0.031	-10000	0	-0.49	2	2
ITGB7	-0.033	0.16	-10000	0	-0.54	44	44
ARF6/GDP	0.006	0.017	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.072	0.17	-10000	0	-0.54	15	15
p130Cas/Crk/Dock1	-0.003	0.035	-10000	0	-0.36	5	5
VCAM1	-0.13	0.25	-10000	0	-0.56	132	132
alpha4/beta1 Integrin/Paxillin/Talin	0.008	0.099	-10000	0	-0.47	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.008	0.099	-10000	0	-0.47	2	2
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
mol:GDP	0.03	0.084	0.46	2	-10000	0	2
CBL	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GIT1	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.008	0.099	-10000	0	-0.47	2	2
Rac1/GTP	0.004	0.041	-10000	0	-0.41	1	1

×

S1P4 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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.06	-9999	-0.59	5	5
CDC42/GTP	-0.012	0.049	-9999	-0.38	3	3
PLCG1	0.03	0.061	-9999	-0.4	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
cell migration	-0.011	0.048	-9999	-0.38	3	3
S1PR5	-0.13	0.25	-9999	-0.55	132	132
S1PR4	0	0.086	-9999	-0.51	14	14
MAPK3	0.03	0.061	-9999	-0.4	3	3
MAPK1	0.03	0.061	-9999	-0.4	3	3
S1P/S1P5/Gi	-0.033	0.13	-9999	-0.58	8	8
GNAI1	-0.005	0.1	-9999	-0.59	16	16
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.086	0.15	-9999	-0.34	132	132
RHOA	0.026	0.048	-9999	-0.3	4	4
S1P/S1P4/Gi	0.023	0.064	-9999	-0.31	9	9
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.014	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.008	0.046	-9999	-0.32	4	4
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.098	-9999	-0.65	4	4
CRKL	0.035	0.074	-9999	-0.46	4	4
mol:DAG	0.04	0.078	-9999	-0.47	5	5
HRAS	0.057	0.075	-9999	-0.6	2	2
MAPK8	0.015	0.097	-9999	-0.37	22	22
RAP1A	0.035	0.073	-9999	-0.46	4	4
GAB1	0.034	0.079	-9999	-0.53	4	4
MAPK14	0.024	0.073	-9999	-0.35	9	9
EPO	-0.005	0.099	-9999	-0.5	20	20
PLCG1	0.04	0.08	-9999	-0.48	5	5
EPOR/TRPC2/IP3 Receptors	0.015	0.024	-9999	-0.52	1	1
RAPGEF1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.062	0.16	-9999	-0.33	127	127
GAB1/SHC/GRB2/SOS1	-0.015	0.062	-9999	-0.51	4	4
EPO/EPOR (dimer)	0.01	0.077	-9999	-0.36	20	20
IRS2	0.034	0.079	-9999	-0.53	4	4
STAT1	0.043	0.097	-9999	-0.5	8	8
STAT5B	0.045	0.083	-9999	-0.43	8	8
cell proliferation	0.023	0.091	-9999	-0.37	17	17
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.016	0.067	-9999	-0.47	6	6
TEC	0.026	0.094	-9999	-0.44	10	10
SOCS3	-0.11	0.23	-9999	-0.52	124	124
STAT1 (dimer)	0.043	0.095	-9999	-0.48	8	8
JAK2	0.015	0.007	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.042	0.08	-9999	-0.49	4	4
EPO/EPOR	0.01	0.077	-9999	-0.36	20	20
LYN	0.006	0.073	-9999	-0.51	10	10
TEC/VAV2	0.035	0.092	-9999	-0.42	10	10
elevation of cytosolic calcium ion concentration	0.015	0.024	-9999	-0.51	1	1
SHC1	0.009	0.05	-9999	-0.49	5	5
EPO/EPOR (dimer)/LYN	0.022	0.083	-9999	-0.31	29	29
mol:IP3	0.04	0.078	-9999	-0.47	5	5
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.043	0.084	-9999	-0.44	9	9
SH2B3	0.013	0.032	-9999	-0.48	2	2
NFKB1	0.024	0.073	-9999	-0.33	11	11
EPO/EPOR (dimer)/JAK2/SOCS3	-0.039	0.074	-9999	-0.24	38	38
PTPN6	0.028	0.076	-9999	-0.49	4	4
TEC/VAV2/GRB2	0.04	0.09	-9999	-0.41	9	9
EPOR	0.015	0.024	-9999	-0.52	1	1
INPP5D	0.008	0.06	-9999	-0.54	6	6
mol:GDP	-0.015	0.063	-9999	-0.52	4	4
SOS1	0.014	0	-9999	-10000	0	0
PLCG2	0	0.088	-9999	-0.55	13	13
CRKL/CBL/C3G	0.049	0.07	-9999	-0.42	4	4
VAV2	0.035	0.073	-9999	-0.46	4	4
CBL	0.035	0.073	-9999	-0.46	4	4
SHC/Grb2/SOS1	-0.015	0.061	-9999	-0.45	5	5
STAT5A	0.037	0.11	-9999	-0.52	13	13
GRB2	0.013	0.022	-9999	-0.49	1	1
STAT5 (dimer)	0.056	0.12	-9999	-0.57	10	10
LYN/PLCgamma2	0.005	0.093	-9999	-0.47	18	18
PTPN11	0.014	0	-9999	-10000	0	0
BTK	0.023	0.11	-9999	-0.49	15	15
BCL2	0.052	0.15	-9999	-0.92	9	9

×

p38 MAPK 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
TRAF6/ASK1	0.01	0.04	-10000	0	-0.31	8	8
TRAF2/ASK1	-0.005	0.042	-10000	0	-0.36	7	7
ATM	0.014	0	-10000	0	-10000	0	0
MAP2K3	0.02	0.054	-10000	0	-0.3	3	3
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.019	0.071	-10000	0	-0.41	7	7
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.031	0.15	-10000	0	-0.54	42	42
TXN	0.009	0.01	-10000	0	-0.21	1	1
CALM1	0.012	0.035	-10000	0	-0.54	2	2
GADD45A	-0.017	0.12	-10000	0	-0.49	32	32
GADD45B	-0.027	0.14	-10000	0	-0.52	39	39
MAP3K1	0.007	0.059	-10000	0	-0.49	7	7
MAP3K6	0.006	0.062	-10000	0	-0.49	8	8
MAP3K7	0.014	0	-10000	0	-10000	0	0
MAP3K4	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.011	0.065	-10000	0	-0.38	15	15
TAK1/TAB family	0.003	0.026	0.18	9	-0.17	1	10
RAC1/OSM/MEKK3	0	0.011	-10000	0	-0.25	1	1
TRAF2	0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.027	-10000	0	-10000	0	0
TRAF6	0.009	0.016	-10000	0	-0.36	1	1
RAC1	0.014	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.071	0.2	-10000	0	-0.54	79	79
CCM2	0.013	0.022	-10000	0	-0.49	1	1
CaM/Ca2+/CAMKIIB	-0.052	0.12	-10000	0	-0.34	79	79
MAPK11	0.004	0.08	-10000	0	-0.59	9	9
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.05	0.12	-10000	0	-0.31	82	82
OSM/MEKK3	-0.001	0.015	-10000	0	-0.34	1	1
TAOK1	-0.015	0.11	-10000	0	-0.35	46	46
TAOK2	0.019	0	-10000	0	-10000	0	0
TAOK3	0.019	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.014	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.006	0.07	-10000	0	-0.59	7	7
MAP3K10	0.005	0.066	-10000	0	-0.49	9	9
MAP3K3	0.014	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.047	-10000	0	-0.38	7	7
GADD45/MTK1/MTK1	-0.056	0.13	-10000	0	-0.37	50	50

×

Nectin adhesion 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
PDGFRB	0.011	0.038	-9999	-0.49	3	3
alphaV beta3 Integrin	-0.046	0.12	-9999	-0.36	66	66
PTK2	-0.03	0.099	-9999	-0.48	19	19
positive regulation of JNK cascade	-0.009	0.045	-9999	-0.31	10	10
CDC42/GDP	0.046	0.073	-9999	-0.41	10	10
Rac1/GDP	0.048	0.073	-9999	-0.41	10	10
RAP1B	0.013	0.022	-9999	-0.49	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.014	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.055	-9999	-0.38	10	10
nectin-3/I-afadin	-0.008	0.059	-9999	-0.43	10	10
RAPGEF1	0.04	0.081	-9999	-0.46	10	10
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.033	0.09	-9999	-0.53	10	10
PDGFB-D/PDGFRB	0.011	0.038	-9999	-0.49	3	3
TLN1	0.032	0.029	-9999	-10000	0	0
Rap1/GTP	-0.009	0.048	-9999	-0.32	10	10
IQGAP1	0.004	0.076	-9999	-0.53	10	10
Rap1/GTP/I-afadin	-0.001	0.018	-9999	-0.32	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.008	0.059	-9999	-0.43	10	10
PVR	0.014	0	-9999	-10000	0	0
Necl-5(dimer)	0.014	0	-9999	-10000	0	0
mol:GDP	0.044	0.087	-9999	-0.51	10	10
MLLT4	0.013	0.027	-9999	-0.59	1	1
PIK3CA	0.013	0.027	-9999	-0.59	1	1
PI3K	-0.008	0.049	-9999	-0.6	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.014	0.076	-9999	-0.43	17	17
positive regulation of lamellipodium assembly	-0.009	0.047	-9999	-0.32	10	10
PVRL1	-0.005	0.1	-9999	-0.59	16	16
PVRL3	0.004	0.08	-9999	-0.59	9	9
PVRL2	0.012	0.035	-9999	-0.54	2	2
PIK3R1	0.014	0	-9999	-10000	0	0
CDH1	-0.12	0.24	-9999	-0.54	127	127
CLDN1	-0.019	0.13	-9999	-0.53	31	31
JAM-A/CLDN1	-0.029	0.091	-9999	-0.35	27	27
SRC	-0.019	0.088	-9999	-0.6	10	10
ITGB3	-0.052	0.18	-9999	-0.51	65	65
nectin-1(dimer)/I-afadin/I-afadin	-0.014	0.076	-9999	-0.43	17	17
FARP2	0.037	0.085	-9999	-0.5	10	10
RAC1	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.007	0.049	-9999	-0.36	10	10
nectin-1/I-afadin	-0.014	0.076	-9999	-0.43	17	17
nectin-2/I-afadin	-0.002	0.031	-9999	-0.4	3	3
RAC1/GTP/IQGAP1/filamentous actin	-0.006	0.044	-9999	-0.32	10	10
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.018	0.081	-9999	-0.37	25	25
CDC42/GTP/IQGAP1/filamentous actin	-0.006	0.044	-9999	-0.32	10	10
F11R	0.002	0.078	-9999	-0.5	12	12
positive regulation of filopodium formation	-0.009	0.045	-9999	-0.31	10	10
alphaV/beta3 Integrin/Talin	0.012	0.094	-9999	-0.4	4	4
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.031	-9999	-0.4	3	3
nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.4	3	3
PIP5K1C	0.025	0.031	-9999	-10000	0	0
VAV2	0.037	0.086	-9999	-0.51	10	10
RAP1/GDP	-0.011	0.055	-9999	-0.38	10	10
ITGAV	0.013	0.027	-9999	-0.59	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.008	0.053	-9999	-0.35	12	12
nectin-3(dimer)/I-afadin/I-afadin	-0.008	0.059	-9999	-0.43	10	10
Rac1/GTP	-0.01	0.057	-9999	-0.39	10	10
PTPRM	0.017	0.034	-9999	-0.22	10	10
E-cadherin/beta catenin/alpha catenin	-0.069	0.12	-9999	-0.58	9	9
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Canonical NF-kappaB 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
FBXW11	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.086	0.03	-9999	-10000	0	0
ERC1	0.013	0.022	-9999	-0.49	1	1
RIP2/NOD2	-0.022	0.088	-9999	-0.37	30	30
NFKBIA	0.05	0	-9999	-10000	0	0
BIRC2	0.014	0	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.007	0.032	-9999	-10000	0	0
IKK complex/A20	-0.071	0.1	-9999	-0.45	7	7
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.046	0.041	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.024	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.001	0.016	-9999	-0.36	1	1
NOD2	-0.017	0.13	-9999	-0.53	30	30
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.018	0	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0	-9999	-10000	0	0
TNF/TNFR1A	-0.12	0.18	-9999	-0.39	165	165
TRAF6	0.013	0.027	-9999	-0.59	1	1
PRKCA	0.013	0.027	-9999	-0.59	1	1
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.15	0.26	-9999	-0.54	156	156
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.05	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.018	0	-9999	-10000	0	0
TNFRSF1A	0.001	0.086	-9999	-0.55	12	12
IKK complex	0.053	0.04	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.026	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.034	0.03	-9999	-0.29	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.013	0.022	-9999	-0.49	1	1
STAT1 (dimer)/Cbp/p300	0.044	0.095	-9999	-0.43	12	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.003	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.077	-9999	-0.32	21	21
CaM/Ca2+	-0.003	0.025	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.034	0.062	-9999	-0.33	6	6
AKT1	0.052	0.028	-9999	-10000	0	0
MAP2K1	0.046	0.044	-9999	-10000	0	0
MAP3K11	0.041	0.028	-9999	-10000	0	0
IFNGR1	0.015	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.19	-9999	-0.46	106	106
Rap1/GTP	-0.002	0.016	-9999	-10000	0	0
CRKL/C3G	-0.001	0.015	-9999	-0.34	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0	0.024	-9999	-10000	0	0
CEBPB	0.058	0.11	-9999	-0.53	10	10
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.001	0.17	-9999	-1	10	10
STAT1	0.034	0.063	-9999	-0.33	6	6
CALM1	0.012	0.035	-9999	-0.54	2	2
IFN-gamma (dimer)	0.001	0.049	-9999	-0.49	5	5
PIK3CA	0.013	0.027	-9999	-0.59	1	1
STAT1 (dimer)/PIAS1	0.038	0.065	-9999	-0.38	1	1
CEBPB/PTGES2/Cbp/p300	-0.015	0.061	-9999	-0.36	9	9
mol:Ca2+	0.022	0.03	-9999	-0.29	1	1
MAPK3	0.054	0.05	-9999	-10000	0	0
STAT1 (dimer)	-0.072	0.11	-9999	-0.46	21	21
MAPK1	0.054	0.05	-9999	-10000	0	0
JAK2	0.015	0.003	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.015	0.003	-9999	-10000	0	0
CAMK2D	0.013	0.027	-9999	-0.59	1	1
DAPK1	0.049	0.13	-9999	-0.63	18	18
SMAD7	0.005	0.065	-9999	-0.19	4	4
CBL/CRKL/C3G	0.037	0.033	-9999	-10000	0	0
PI3K	-0.002	0.021	-9999	-10000	0	0
IFNG	0.001	0.049	-9999	-0.49	5	5
apoptosis	0.03	0.097	-9999	-0.45	18	18
CAMK2G	0.013	0.027	-9999	-0.59	1	1
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.23	0.28	-9999	-0.54	228	228
CAMK2B	-0.071	0.2	-9999	-0.54	79	79
FRAP1	0.05	0.027	-9999	-10000	0	0
PRKCD	0.038	0.073	-9999	-10000	0	0
RAP1B	0.013	0.022	-9999	-0.49	1	1
negative regulation of cell growth	-0.055	0.077	-9999	-0.32	21	21
PTPN2	0.014	0	-9999	-10000	0	0
EP300	0.01	0.053	-9999	-0.59	4	4
IRF1	0.032	0.15	-9999	-0.57	19	19
STAT1 (dimer)/PIASy	0.04	0.062	-9999	-0.39	1	1
SOCS1	-0.048	0.2	-9999	-0.56	45	45
mol:GDP	-0.001	0.019	-9999	-10000	0	0
CASP1	-0.003	0.089	-9999	-0.28	28	28
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.05	0.047	-9999	-0.24	4	4
mol:PI-3-4-5-P3	-0.002	0.021	-9999	-10000	0	0
RAP1/GDP	-0.002	0.017	-9999	-10000	0	0
CBL	0.041	0.027	-9999	-10000	0	0
MAP3K1	0.038	0.042	-9999	-10000	0	0
PIAS1	0.009	0.053	-9999	-0.59	4	4
PIAS4	0.014	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.077	-9999	-0.32	21	21
PTPN11	0.034	0.028	-9999	-0.29	1	1
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.012	0.044	-9999	-10000	0	0
DAPP1	-0.034	0.14	-9999	-0.48	26	26
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.083	0.22	-9999	-0.6	47	47
mol:DAG	-0.025	0.11	-9999	-0.29	26	26
HRAS	0.014	0.003	-9999	-10000	0	0
RAP1A	0.014	0.003	-9999	-10000	0	0
ARF5/GDP	0.03	0.057	-9999	-0.29	6	6
PLCG2	0	0.088	-9999	-0.55	13	13
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.014	0.051	-9999	-10000	0	0
ARF1/GTP	-0.011	0.041	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.009	0.053	-9999	-0.59	4	4
RAP1A/GTP	-0.013	0.05	-9999	-10000	0	0
ADAP1	-0.029	0.085	-9999	-0.47	8	8
ARAP3	-0.014	0.051	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.002	0.084	-9999	-0.59	10	10
ARHGEF6	0.008	0.06	-9999	-0.59	5	5
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.014	0.003	-9999	-10000	0	0
FYN	0.014	0	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.011	0.038	-9999	-0.49	3	3
mol:Ca2+	-0.003	0.057	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.013	0.027	-9999	-0.59	1	1
ZAP70	-0.046	0.17	-9999	-0.53	57	57
mol:IP3	-0.009	0.076	-9999	-0.22	9	9
LYN	0.004	0.073	-9999	-0.51	10	10
ARF1/GDP	0.03	0.057	-9999	-0.29	6	6
RhoA/GDP	-0.013	0.043	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.022	-9999	-0.36	2	2
BLNK	-0.056	0.19	-9999	-0.57	61	61
actin cytoskeleton reorganization	0.044	0.074	-9999	-0.38	5	5
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.028	0.038	-9999	-0.32	6	6
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0.001	0.027	-9999	-0.57	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.012	0.044	-9999	-10000	0	0
RhoA/GTP	-0.012	0.046	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.077	0.2	-9999	-0.53	52	52
BLK	-0.11	0.22	-9999	-0.52	114	114
PDPK1	0.012	0.038	-9999	-0.59	2	2
CYTH1	-0.012	0.046	-9999	-10000	0	0
HCK	-0.007	0.11	-9999	-0.54	20	20
CYTH3	-0.012	0.046	-9999	-10000	0	0
CYTH2	-0.012	0.046	-9999	-10000	0	0
KRAS	0.013	0.022	-9999	-0.49	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.026	0.085	-9999	-0.45	13	13
SGK1	-0.02	0.081	-9999	-0.49	13	13
INPP5D	0.008	0.06	-9999	-0.54	6	6
mol:GDP	0.023	0.059	-9999	-0.31	6	6
SOS1	0.014	0	-9999	-10000	0	0
SYK	-0.013	0.12	-9999	-0.57	24	24
ARF6/GDP	-0.013	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.013	0.05	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.014	0.051	-9999	-10000	0	0
VAV1	-0.019	0.14	-9999	-0.56	30	30
mol:PI-3-4-P2	0.02	0.044	-9999	-0.38	6	6
RAS family/GTP/PI3K Class I	0.018	0.059	-9999	-10000	0	0
PLEKHA1	0.024	0.05	-9999	-0.3	12	12
Rac1/GDP	0.03	0.057	-9999	-0.29	6	6
LAT	-0.017	0.13	-9999	-0.59	27	27
Rac1/GTP	0.024	0.085	-9999	-0.45	10	10
ITK	-0.063	0.12	-9999	-0.42	20	20
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.041	0.14	-9999	-0.42	27	27
LCK	-0.081	0.21	-9999	-0.54	89	89
BTK	-0.023	0.069	-9999	-0.42	1	1

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.011	0.038	-10000	0	-0.49	3	3
mol:Halofuginone	0.005	0.01	-10000	0	-0.23	1	1
ITGA1	-0.012	0.12	-10000	0	-0.52	25	25
CDKN1A	-0.024	0.11	-10000	0	-0.44	22	22
PRL-3/alpha Tubulin	-0.003	0.034	-10000	0	-0.34	5	5
mol:Ca2+	-0.02	0.095	0.23	3	-0.43	25	28
AGT	-0.015	0.13	-10000	0	-0.58	25	25
CCNA2	-0.057	0.16	-10000	0	-0.52	15	15
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	-0.064	0.17	-10000	0	-0.38	116	116
CDK2/Cyclin E1	-0.014	0.12	-10000	0	-0.41	24	24
MAPK3	0.021	0.036	-10000	0	-0.34	5	5
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.036	-10000	0	-0.34	5	5
PTP4A1	-0.031	0.14	-10000	0	-0.95	1	1
PTP4A3	0.009	0.05	-10000	0	-0.49	5	5
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.02	0.043	-10000	0	-0.34	7	7
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.003	0.062	-10000	0	-0.27	1	1
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.025	0.13	-10000	0	-0.89	1	1
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.001	0.03	0.23	5	-0.44	1	6
RHOC	0.002	0.065	-10000	0	-0.33	2	2
RHOA	0.003	0.062	-10000	0	-0.27	1	1
cell motility	0.006	0.066	-10000	0	-0.3	1	1
PRL-1/alpha Tubulin	-0.022	0.13	-10000	0	-0.89	1	1
PRL-3/alpha1 Integrin	-0.021	0.088	-10000	0	-0.38	29	29
ROCK1	0.006	0.066	-10000	0	-0.3	1	1
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0	0.086	-10000	0	-0.53	13	13
mitosis	-0.031	0.14	-10000	0	-0.94	1	1
ATF5	0.007	0.059	-10000	0	-0.49	7	7

×

Circadian rhythm 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.032	0.085	-10000	0	-0.54	6	6
CLOCK	-0.018	0.14	-10000	0	-0.59	30	30
TIMELESS/CRY2	0.025	0.082	-10000	0	-0.63	1	1
DEC1/BMAL1	0.008	0.059	-10000	0	-0.34	14	14
ATR	0.014	0	-10000	0	-10000	0	0
NR1D1	0.025	0.12	-10000	0	-1.3	3	3
ARNTL	0.014	0.04	-10000	0	-0.5	3	3
TIMELESS	0.025	0.081	-10000	0	-10000	0	0
NPAS2	0.006	0.079	-10000	0	-0.55	10	10
CRY2	0.008	0.06	-10000	0	-0.59	5	5
mol:CO	-0.012	0.019	0.084	16	-10000	0	16
CHEK1	0.008	0.054	-10000	0	-0.49	6	6
mol:HEME	0.012	0.019	-10000	0	-0.084	16	16
PER1	0.004	0.08	-10000	0	-0.59	9	9
BMAL/CLOCK/NPAS2	0.013	0.11	-10000	0	-0.35	42	42
BMAL1/CLOCK	0.015	0.13	-10000	0	-0.73	6	6
S phase of mitotic cell cycle	0.032	0.085	-10000	0	-0.54	6	6
TIMELESS/CHEK1/ATR	0.033	0.086	-10000	0	-0.55	6	6
mol:NADPH	0.012	0.019	-10000	0	-0.084	16	16
PER1/TIMELESS	0.022	0.085	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.002	0.073	-10000	0	-0.49	11	11

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.085	0.13	-10000	0	-0.35	79	79
Ran/GTP/Exportin 1/HDAC1	-0.002	0.023	-10000	0	-0.26	4	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.034	0.14	-10000	0	-0.31	79	79
SUMO1	0.014	0	-10000	0	-10000	0	0
ZFPM1	0.013	0.027	-10000	0	-0.59	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-10000	0	-10000	0	0
FKBP3	0.014	0	-10000	0	-10000	0	0
Histones	-0.005	0.087	-10000	0	-0.44	4	4
YY1/LSF	0.031	0.03	-10000	0	-0.34	1	1
SMG5	0.013	0.022	-10000	0	-0.49	1	1
RAN	0.014	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.041	0.12	-10000	0	-0.27	76	76
I kappa B alpha/HDAC1	-0.024	0.094	-10000	0	-0.39	7	7
SAP18	0.014	0	-10000	0	-10000	0	0
RELA	-0.031	0.11	-10000	0	-0.25	79	79
HDAC1/Smad7	-0.003	0.031	-10000	0	-0.36	4	4
RANGAP1	0.014	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.021	0.086	-10000	0	-0.29	3	3
NuRD/MBD3 Complex	0.05	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.022	0.1	-10000	0	-0.35	6	6
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.004	0.1	-10000	0	-0.56	16	16
GATA1	0.004	0.058	-10000	0	-0.49	7	7
Mad/Max	0	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.058	0.029	-10000	0	-10000	0	0
RBBP7	0.014	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0.013	0.027	-10000	0	-0.59	1	1
MAX	0.014	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
NFKBIA	-0.033	0.096	-10000	0	-0.33	3	3
KAT2B	0.013	0.022	-10000	0	-0.49	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.045	0.026	-10000	0	-10000	0	0
SIN3 complex	-0.001	0.014	-10000	0	-0.32	1	1
SMURF1	0.014	0	-10000	0	-10000	0	0
CHD3	0.013	0.027	-10000	0	-0.59	1	1
SAP30	0.013	0.027	-10000	0	-0.59	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.012	0.038	-10000	0	-0.59	2	2
YY1/HDAC3	-0.007	0.084	-10000	0	-0.28	7	7
YY1/HDAC2	0.032	0.025	-10000	0	-10000	0	0
YY1/HDAC1	0.029	0.041	-10000	0	-0.34	4	4
NuRD/MBD2 Complex (MeCP1)	0.05	0.023	-10000	0	-10000	0	0
PPARG	-0.091	0.14	-10000	0	-0.35	93	93
HDAC8/hEST1B	-0.001	0.02	-10000	0	-0.36	1	1
UBE2I	0.014	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-10000	0	-10000	0	0
TNFRSF1A	0.001	0.086	-10000	0	-0.55	12	12
HDAC3/SMRT (N-CoR2)	-0.021	0.086	-10000	0	-0.29	3	3
MBD3L2	0	0.001	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.003	0.031	-10000	0	-0.36	4	4
CREBBP	0.014	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.024	-10000	0	-10000	0	0
HDAC1	0.009	0.053	-10000	0	-0.59	4	4
HDAC3	-0.033	0.096	-10000	0	-0.33	3	3
HDAC2	0.014	0	-10000	0	-10000	0	0
YY1	0.03	0.029	-10000	0	-0.28	4	4
HDAC8	0.013	0.027	-10000	0	-0.59	1	1
SMAD7	0.014	0	-10000	0	-10000	0	0
NCOR2	0.014	0	-10000	0	-10000	0	0
MXD1	0.014	0	-10000	0	-10000	0	0
STAT3	0.025	0.033	-10000	0	-0.34	4	4
NFKB1	0.014	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.014	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.035	0.04	-10000	0	-0.3	5	5
YY1/SAP30/HDAC1	0.035	0.04	-10000	0	-0.3	5	5
EP300	0.009	0.053	-10000	0	-0.59	4	4
STAT3 (dimer non-phopshorylated)	0.025	0.033	-10000	0	-0.34	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.033	0.096	-10000	0	-0.33	3	3
histone deacetylation	0.05	0.023	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.01	0.085	-10000	0	-0.31	6	6
nuclear export	0.001	0.02	0.36	1	-10000	0	1
PRKACA	0.014	0	-10000	0	-10000	0	0
GATAD2B	0.014	0	-10000	0	-10000	0	0
GATAD2A	0.014	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.031	0.1	-10000	0	-0.36	14	14
GATA1/HDAC1	-0.008	0.055	-10000	0	-0.37	11	11
GATA1/HDAC3	-0.033	0.089	-10000	0	-0.29	10	10
CHD4	0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.12	0.18	-10000	0	-0.39	165	165
SIN3/HDAC complex/Mad/Max	0.05	0.023	-10000	0	-10000	0	0
NuRD Complex	0.058	0.024	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.038	0.065	-10000	0	-0.43	4	4
SIN3B	0.014	0	-10000	0	-10000	0	0
MTA2	0.014	0	-10000	0	-10000	0	0
SIN3A	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.031	0.028	-10000	0	-0.29	4	4
HDAC complex	-0.003	0.031	-10000	0	-0.32	5	5
GATA1/Fog1	-0.006	0.044	-10000	0	-0.35	8	8
FKBP25/HDAC1/HDAC2	-0.003	0.031	-10000	0	-0.36	4	4
TNF	-0.15	0.26	-10000	0	-0.54	156	156
negative regulation of cell growth	0.05	0.023	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.05	0.023	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.044	0.14	-10000	0	-0.33	79	79
SIN3/HDAC complex/NCoR1	0.047	0.03	-10000	0	-0.39	1	1
TFCP2	0.013	0.027	-10000	0	-0.59	1	1
NR2C1	0.014	0	-10000	0	-10000	0	0
MBD3	0.014	0	-10000	0	-10000	0	0
MBD2	0.014	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.004	0.077	0.57	9	-10000	0	9
PI3K Class IB/PDE3B	0.004	0.077	-10000	0	-0.57	9	9
PDE3B	0.004	0.077	-10000	0	-0.57	9	9

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.05	0.21	-10000	0	-0.92	23	23
oxygen homeostasis	0.007	0.017	-10000	0	-10000	0	0
TCEB2	0.014	0	-10000	0	-10000	0	0
TCEB1	0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.005	0.049	-10000	0	-0.31	4	4
EPO	0.092	0.23	-10000	0	-0.72	14	14
FIH (dimer)	0.021	0.017	-10000	0	-10000	0	0
APEX1	0.02	0.017	-10000	0	-10000	0	0
SERPINE1	0.01	0.33	-10000	0	-0.71	33	33
FLT1	-0.003	0.1	-10000	0	-0.9	5	5
ADORA2A	0.09	0.23	-10000	0	-0.71	14	14
germ cell development	0.074	0.25	-10000	0	-0.71	18	18
SLC11A2	0.093	0.23	-10000	0	-0.75	12	12
BHLHE40	0.083	0.26	-10000	0	-0.78	18	18
HIF1AN	0.021	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.024	0.086	-10000	0	-0.44	8	8
ETS1	0.02	0.08	-10000	0	-0.54	10	10
CITED2	0.003	0.037	-10000	0	-0.44	2	2
KDR	-0.012	0.13	-10000	0	-0.86	9	9
PGK1	0.093	0.23	-10000	0	-0.73	13	13
SIRT1	0.015	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.098	0.27	-10000	0	-0.91	13	13
EPAS1	0.066	0.11	-10000	0	-0.35	7	7
SP1	0.019	0.017	-10000	0	-10000	0	0
ABCG2	0.092	0.24	-10000	0	-0.8	12	12
EFNA1	0.091	0.24	-10000	0	-0.76	13	13
FXN	0.091	0.23	-10000	0	-0.72	13	13
POU5F1	0.073	0.26	-10000	0	-0.74	19	19
neuron apoptosis	-0.097	0.26	0.86	13	-10000	0	13
EP300	0.009	0.053	-10000	0	-0.59	4	4
EGLN3	0.006	0.098	-10000	0	-0.59	13	13
EGLN2	0.021	0.017	-10000	0	-10000	0	0
EGLN1	0.021	0.017	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.019	0.029	-10000	0	-0.52	1	1
SLC2A1	0.09	0.23	-10000	0	-0.73	13	13
TWIST1	0.064	0.28	-10000	0	-0.75	26	26
ELK1	0.023	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.024	0.086	-10000	0	-0.44	8	8
VEGFA	0.084	0.26	-10000	0	-0.83	14	14
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.008	0.052	-9999	-0.34	12	12
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.009	0.083	-9999	-0.33	29	29
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.08	-9999	-0.5	2	2
NFKBIA	-0.01	0.091	-9999	-0.3	10	10
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.029	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	-0.018	0.13	-9999	-0.56	29	29
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.047	-9999	-0.28	12	12
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.029	0	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.014	0	-9999	-10000	0	0
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.002	0.087	-9999	-0.44	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.019	0.079	-9999	-0.48	2	2
SRC	0.014	0	-9999	-10000	0	0
PI3K	-0.001	0.019	-9999	-0.43	1	1
NF kappa B1 p50/RelA	-0.002	0.087	-9999	-0.44	2	2
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	-0.013	0.12	-9999	-0.57	24	24
I kappa B alpha/PIK3R1	-0.002	0.085	-9999	-0.54	2	2
cell death	0.018	0.076	-9999	-0.46	2	2
NF kappa B1 p105/c-Rel	0.009	0.083	-9999	-0.33	29	29
LCK	-0.081	0.21	-9999	-0.54	89	89
BCL3	0.002	0.076	-9999	-0.49	12	12

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.046	0.12	-9999	-0.36	66	66
AKT1	0.074	0.085	-9999	-0.64	3	3
PTK2B	-0.002	0.14	-9999	-0.48	23	23
VEGFR2 homodimer/Frs2	0.029	0.074	-9999	-0.72	3	3
CAV1	-0.05	0.17	-9999	-0.49	65	65
CALM1	0.012	0.035	-9999	-0.54	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.018	0.08	-9999	-0.61	5	5
endothelial cell proliferation	0.061	0.1	-9999	-0.49	4	4
mol:Ca2+	0.036	0.093	-9999	-0.55	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.021	0.083	-9999	-0.6	6	6
RP11-342D11.1	0.027	0.092	-9999	-0.56	5	5
CDH5	0.011	0.038	-9999	-0.49	3	3
VEGFA homodimer	-0.012	0.053	-9999	-0.32	1	1
SHC1	0.009	0.05	-9999	-0.49	5	5
SHC2	0.013	0.027	-9999	-0.59	1	1
HRAS/GDP	-0.019	0.072	-9999	-0.49	6	6
SH2D2A	-0.073	0.2	-9999	-0.54	81	81
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.022	0.07	-9999	-0.48	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.06	0.14	-9999	-0.59	15	15
VEGFR1 homodimer	0.013	0.027	-9999	-0.59	1	1
SHC/GRB2/SOS1	-0.021	0.08	-9999	-0.51	8	8
GRB10	0.034	0.1	-9999	-0.57	7	7
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-0.49	1	1
PAK1	-0.035	0.15	-9999	-0.5	49	49
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.021	0.088	-9999	-0.62	7	7
HRAS	0.014	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.027	0.079	-9999	-0.37	5	5
HIF1A	0.012	0.035	-9999	-0.54	2	2
FRS2	0.012	0.035	-9999	-0.54	2	2
oxygen and reactive oxygen species metabolic process	-0.021	0.082	-9999	-0.59	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.071	-9999	-0.52	9	9
Nck/Pak	-0.034	0.1	-9999	-0.35	50	50
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.017	0.079	-9999	-0.61	5	5
mol:GDP	-0.021	0.078	-9999	-0.5	8	8
mol:NADP	0.061	0.081	-9999	-0.43	5	5
eNOS/Hsp90	0.065	0.077	-9999	-0.41	4	4
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.036	0.094	-9999	-0.56	5	5
HIF1A/ARNT	-0.002	0.028	-9999	-0.37	3	3
SHB	0.014	0	-9999	-10000	0	0
VEGFA	-0.005	0.1	-9999	-0.48	22	22
VEGFC	-0.004	0.096	-9999	-0.52	17	17
FAK1/Vinculin	0.035	0.12	-9999	-0.62	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.046	0.12	-9999	-0.5	22	22
PTPN6	-0.004	0.099	-9999	-0.55	16	16
EPAS1	0.02	0.038	-9999	-0.34	3	3
mol:L-citrulline	0.061	0.081	-9999	-0.43	5	5
ITGAV	0.013	0.027	-9999	-0.59	1	1
PIK3CA	0.013	0.027	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.018	0.075	-9999	-0.58	5	5
VEGFR2 homodimer/VEGFA homodimer	-0.024	0.086	-9999	-0.61	5	5
VEGFR2/3 heterodimer	0.025	0.091	-9999	-0.73	5	5
VEGFB	0.013	0.022	-9999	-0.49	1	1
MAPK11	0.035	0.099	-9999	-0.53	7	7
VEGFR2 homodimer	0.029	0.081	-9999	-0.54	9	9
FLT1	0.013	0.027	-9999	-0.59	1	1
NEDD4	0.005	0.078	-9999	-0.52	11	11
MAPK3	0.029	0.098	-9999	-0.5	5	5
MAPK1	0.029	0.098	-9999	-0.5	5	5
VEGFA145/NRP2	-0.022	0.089	-9999	-0.37	31	31
VEGFR1/2 heterodimer	0.03	0.072	-9999	-0.72	3	3
KDR	0.029	0.081	-9999	-0.54	9	9
VEGFA165/NRP1/VEGFR2 homodimer	0.029	0.1	-9999	-0.53	6	6
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.031	0.099	-9999	-0.49	6	6
PI3K	0.061	0.092	-9999	-0.67	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.018	0.08	-9999	-0.61	5	5
FES	0.034	0.098	-9999	-0.55	6	6
GAB1	-0.017	0.074	-9999	-0.62	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.017	0.079	-9999	-0.61	5	5
CTNNB1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.013	0.022	-9999	-0.49	1	1
eNOS/Caveolin-1	0.038	0.11	-9999	-0.48	6	6
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.02	0.085	-9999	-0.6	6	6
PI3K/GAB1	0.075	0.085	-9999	-0.54	4	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.036	0.09	-9999	-0.55	6	6
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.018	0.094	-9999	-0.64	7	7
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.036	0.095	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.06	0.14	-9999	-0.58	15	15
PTK2	0.031	0.11	-9999	-0.62	5	5
EDG1	0.027	0.092	-9999	-0.56	5	5
mol:DAG	0.036	0.094	-9999	-0.56	5	5
CaM/Ca2+	-0.02	0.071	-9999	-0.51	5	5
MAP2K3	0.034	0.11	-9999	-0.55	7	7
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.034	0.1	-9999	-0.58	7	7
PLCG1	0.036	0.095	-9999	-0.57	5	5
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.016	0.073	-9999	-0.58	5	5
IQGAP1	0.004	0.076	-9999	-0.53	10	10
YES1	0.009	0.053	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.017	0.079	-9999	-0.61	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.026	0.094	-9999	-0.59	7	7
cell migration	0.057	0.11	-9999	-0.56	7	7
mol:PI-3-4-5-P3	0.06	0.087	-9999	-0.61	3	3
FYN	0.014	0	-9999	-10000	0	0
VEGFB/NRP1	0.033	0.088	-9999	-0.52	5	5
mol:NO	0.061	0.081	-9999	-0.43	5	5
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.019	0.072	-9999	-0.49	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.034	0.1	-9999	-0.58	7	7
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.052	0.18	-9999	-0.51	65	65
NOS3	0.062	0.088	-9999	-0.49	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.018	0.082	-9999	-0.61	6	6
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.043	0.089	-9999	-0.52	5	5
PRKCB	0.005	0.14	-9999	-0.5	18	18
VCL	0.008	0.058	-9999	-0.52	6	6
VEGFA165/NRP1	0.027	0.093	-9999	-0.56	5	5
VEGFR1/2 heterodimer/VEGFA homodimer	-0.018	0.08	-9999	-0.61	5	5
VEGFA165/NRP2	-0.022	0.089	-9999	-0.37	31	31
MAPKKK cascade	0.057	0.098	-9999	-0.52	7	7
NRP2	0.003	0.08	-9999	-0.56	10	10
VEGFC homodimer	-0.004	0.096	-9999	-0.52	17	17
NCK1	0.013	0.027	-9999	-0.59	1	1
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.038	0.11	-9999	-0.57	5	5
MAP3K13	0.028	0.11	-9999	-0.56	6	6
PDPK1	0.065	0.085	-9999	-0.6	3	3

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.052	-9999	-0.57	1	1
TC10/GTP	-0.007	0.046	-9999	-0.55	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.027	-9999	-0.29	4	4
HRAS	0.014	0	-9999	-10000	0	0
APS homodimer	0	0.089	-9999	-0.57	12	12
GRB14	-0.18	0.26	-9999	-0.53	184	184
FOXO3	-0.026	0.091	-9999	-0.58	13	13
AKT1	-0.039	0.13	-9999	-0.45	4	4
INSR	0.016	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin	0.036	0.028	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.011	0.044	-9999	-0.56	3	3
SORBS1	0.011	0.046	-9999	-0.59	3	3
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.035	0.028	-9999	-10000	0	0
CAV1	-0.007	0.097	-9999	-0.37	6	6
CBL/APS/CAP/Crk-II/C3G	-0.008	0.051	-9999	-0.6	1	1
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.027	-9999	-0.29	4	4
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.026	-9999	-0.28	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.032	-9999	-10000	0	0
RPS6KB1	-0.028	0.12	-9999	-0.4	4	4
PARD6A	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.038	-9999	-0.82	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.064	0.088	-9999	-0.4	4	4
HRAS/GTP	-0.006	0.037	-9999	-0.42	1	1
Insulin Receptor	0.016	0.003	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.005	0.035	-9999	-10000	0	0
PRKCI	-0.022	0.053	-9999	-0.55	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.081	0.11	-9999	-0.48	4	4
SHC1	0.009	0.05	-9999	-0.49	5	5
negative regulation of MAPKKK cascade	-0.001	0.035	-9999	-0.7	1	1
PI3K	-0.003	0.027	-9999	-0.29	1	1
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.039	0.13	-9999	-0.45	4	4
PRKCZ	-0.043	0.12	-9999	-0.59	20	20
SH2B2	0	0.089	-9999	-0.57	12	12
SHC/SHIP	0.029	0.05	-9999	-0.34	4	4
F2RL2	-0.094	0.21	-9999	-0.51	105	105
TRIP10	0.007	0.065	-9999	-0.55	7	7
Insulin Receptor/Insulin/Shc	-0.005	0.038	-9999	-0.28	9	9
TC10/GTP/CIP4/Exocyst	-0.005	0.039	-9999	-0.33	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.005	0.035	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.014	0	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
CBL/APS/CAP/Crk-II	-0.009	0.056	-9999	-0.34	12	12
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.007	0.044	-9999	-0.3	6	6
INPP5D	0.023	0.046	-9999	-0.32	7	7
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.027	0.14	-9999	-0.87	13	13
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.014	0	-9999	-10000	0	0
p62DOK/RasGAP	-0.001	0.036	-9999	-0.71	1	1
INS	-0.002	0.056	-9999	-0.57	5	5
mol:PI-3-4-P2	0.023	0.046	-9999	-0.32	7	7
GRB2	0.013	0.022	-9999	-0.49	1	1
EIF4EBP1	-0.034	0.13	-9999	-0.42	12	12
PTPRA	0.016	0.003	-9999	-10000	0	0
PIK3CA	0.013	0.027	-9999	-0.59	1	1
TC10/GTP/CIP4	-0.005	0.039	-9999	-0.33	7	7
PDPK1	0.012	0.038	-9999	-0.59	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.031	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.028	-9999	-0.3	4	4
Insulin Receptor/Insulin/IRS3	-0.004	0.04	-9999	-0.4	5	5
Par3/Par6	-0.054	0.1	-9999	-0.31	28	28

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.032	0.042	-9999	-0.72	1	1
VEGFR1 homodimer/NRP1	0.022	0.039	-9999	-0.54	2	2
mol:DAG	-0.02	0.13	-9999	-0.66	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.013	0.06	-9999	-0.67	1	1
CaM/Ca2+	-0.012	0.12	-9999	-0.57	2	2
HIF1A	0.02	0.038	-9999	-0.46	3	3
GAB1	0.012	0.035	-9999	-0.54	2	2
AKT1	0.005	0.13	-9999	-0.71	2	2
PLCG1	-0.02	0.13	-9999	-0.66	1	1
NOS3	0.007	0.13	-9999	-0.53	2	2
CBL	0.014	0	-9999	-10000	0	0
mol:NO	0.008	0.12	-9999	-0.47	3	3
FLT1	0.03	0.045	-9999	-0.62	2	2
PGF	-0.092	0.22	-9999	-0.55	96	96
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.082	-9999	-0.58	2	2
CALM1	0.012	0.035	-9999	-0.54	2	2
PIK3CA	0.013	0.027	-9999	-0.59	1	1
eNOS/Hsp90	0.015	0.12	-9999	-0.49	2	2
endothelial cell proliferation	-0.033	0.16	-9999	-0.52	17	17
mol:Ca2+	-0.02	0.13	-9999	-0.65	1	1
MAPK3	-0.001	0.12	-9999	-0.57	1	1
MAPK1	-0.001	0.12	-9999	-0.57	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
PLGF homodimer	-0.092	0.22	-9999	-0.55	96	96
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.05	0.17	-9999	-0.49	65	65
VEGFA homodimer	-0.007	0.1	-9999	-0.49	22	22
VEGFR1 homodimer/VEGFA homodimer	0.019	0.073	-9999	-0.72	1	1
platelet activating factor biosynthetic process	0.007	0.11	-9999	-0.55	1	1
PI3K	-0.011	0.13	-9999	-0.61	2	2
PRKCA	-0.01	0.12	-9999	-0.61	1	1
PRKCB	-0.049	0.16	-9999	-0.55	17	17
VEGFR1 homodimer/PLGF homodimer	-0.034	0.14	-9999	-0.72	1	1
VEGFA	-0.007	0.1	-9999	-0.49	22	22
VEGFB	0.013	0.022	-9999	-0.49	1	1
mol:IP3	-0.02	0.13	-9999	-0.66	1	1
RASA1	0.04	0.039	-9999	-0.66	1	1
NRP2	0.003	0.08	-9999	-0.56	10	10
VEGFR1 homodimer	0.03	0.045	-9999	-0.61	2	2
VEGFB homodimer	0.013	0.022	-9999	-0.49	1	1
NCK1	0.013	0.027	-9999	-0.59	1	1
eNOS/Caveolin-1	-0.015	0.14	-9999	-0.47	12	12
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.05	0.11	-9999	-0.6	2	2
mol:L-citrulline	0.008	0.12	-9999	-0.47	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.035	0.064	-9999	-0.63	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.027	0.069	-9999	-0.67	1	1
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.048	0.1	-9999	-0.57	2	2
PDPK1	-0.003	0.12	-9999	-0.71	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.027	0.067	-9999	-0.67	1	1
mol:NADP	0.008	0.12	-9999	-0.47	3	3
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.011	0.053	-9999	-0.62	1	1
VEGFR1 homodimer/NRP2	0.026	0.064	-9999	-0.72	1	1

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-9999	-0.49	3	3
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.06	-9999	-0.27	17	17
GNAO1	0.01	0.06	-9999	-0.6	5	5
S1P/S1P3/G12/G13	0.002	0.09	-9999	-0.35	12	12
AKT1	0.027	0.04	-9999	-0.3	2	2
AKT3	0.027	0.14	-9999	-1.3	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.038	-9999	-0.49	3	3
GNAI2	0.016	0.002	-9999	-10000	0	0
GNAI3	0.016	0.002	-9999	-10000	0	0
GNAI1	-0.003	0.11	-9999	-0.59	16	16
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.033	0.15	-9999	-0.51	47	47
S1PR2	0.007	0.062	-9999	-0.56	6	6
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.019	0.092	-9999	-0.49	7	7
MAPK3	0.027	0.088	-9999	-0.46	7	7
MAPK1	0.027	0.088	-9999	-0.46	7	7
JAK2	0.023	0.096	-9999	-0.42	11	11
CXCR4	0.012	0.11	-9999	-0.44	14	14
FLT1	0.016	0.028	-9999	-0.61	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.027	0.088	-9999	-0.46	7	7
S1P/S1P3/Gi	0.019	0.093	-9999	-0.49	7	7
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.02	0.07	-9999	-0.44	7	7
VEGFA	-0.004	0.1	-9999	-0.49	22	22
S1P/S1P2/Gi	0.031	0.069	-9999	-0.44	5	5
VEGFR1 homodimer/VEGFA homodimer	0.013	0.078	-9999	-0.34	23	23
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.009	0.11	-9999	-0.32	34	34
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	0.016	0.002	-9999	-10000	0	0
G12/G13	-0.001	0.019	-9999	-0.43	1	1
GNA14	-0.014	0.12	-9999	-0.56	25	25
GNA15	-0.007	0.11	-9999	-0.56	19	19
GNA12	0.013	0.027	-9999	-0.59	1	1
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.004	0.08	-9999	-0.59	9	9
Rac1/GTP	-0.02	0.07	-9999	-0.44	7	7

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.002	0.028	-9999	-0.32	4	4
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.005	0.04	-9999	-0.34	7	7
GATA1/HDAC5	-0.005	0.04	-9999	-0.34	7	7
GATA2/HDAC5	-0.012	0.07	-9999	-0.4	16	16
HDAC5/BCL6/BCoR	-0.001	0.012	-9999	-0.28	1	1
HDAC9	-0.002	0.094	-9999	-0.54	15	15
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
GATA2	-0.004	0.1	-9999	-0.56	16	16
HDAC4/RFXANK	-0.001	0.015	-9999	-0.34	1	1
BCOR	0.013	0.022	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	-0.003	0.038	-9999	-0.43	4	4
Histones	0.038	0.036	-9999	-10000	0	0
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.014	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.015	-9999	-0.34	1	1
CAMK4	-0.17	0.27	-9999	-0.56	167	167
Tubulin/HDAC6	-0.001	0.016	-9999	-0.36	1	1
SUMO1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
GATA1	0.004	0.058	-9999	-0.49	7	7
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.019	-9999	-0.43	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.015	-9999	-0.34	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.11	0.16	-9999	-0.34	167	167
HDAC4/ER alpha	-0.019	0.084	-9999	-0.38	26	26
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.038	0.036	-9999	-10000	0	0
cell motility	-0.001	0.016	-9999	-0.36	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.014	0.12	-9999	-0.54	26	26
HDAC6/HDAC11	-0.001	0.019	-9999	-0.43	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.008	0.1	-9999	-0.5	22	22
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.01	0.046	-9999	-10000	0	0
GNG2	0.009	0.053	-9999	-0.59	4	4
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.013	0.027	-9999	-0.59	1	1
HDAC11	0.013	0.027	-9999	-0.59	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.014	0	-9999	-10000	0	0
RFXANK	0.013	0.022	-9999	-0.49	1	1
nuclear import	-0.032	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.009	0.053	-9999	-0.59	4	4
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.008	0.052	-9999	-0.36	11	11
forebrain development	-0.006	0.15	-9999	-0.43	42	42
GNAO1	0.008	0.06	-9999	-0.6	5	5
SMO/beta Arrestin2	0.016	0.053	-9999	-0.43	7	7
SMO	0.006	0.07	-9999	-0.59	7	7
ARRB2	0.014	0.004	-9999	-10000	0	0
GLI3/SPOP	0.04	0.066	-9999	-0.6	1	1
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.013	0.027	-9999	-0.59	1	1
GNAI2	0.014	0.003	-9999	-10000	0	0
SIN3/HDAC complex	0.004	0.019	-9999	-0.32	1	1
GNAI1	-0.005	0.1	-9999	-0.59	16	16
XPO1	0.015	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.043	0.11	-9999	-0.55	11	11
SAP30	0.013	0.027	-9999	-0.59	1	1
mol:GDP	0.006	0.07	-9999	-0.59	7	7
MIM/GLI2A	0.01	0.059	-9999	-0.58	5	5
IFT88	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0.003	-9999	-10000	0	0
GLI2	0.043	0.036	-9999	-10000	0	0
GLI3	0.034	0.07	-9999	-0.48	2	2
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0	-9999	-10000	0	0
GNG2	0.009	0.053	-9999	-0.59	4	4
Gi family/GTP	0.024	0.067	-9999	-0.34	6	6
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.052	0.058	-9999	-0.46	2	2
GLI2/Su(fu)	0.053	0.057	-9999	-0.77	1	1
FOXA2	-0.04	0.13	-9999	-0.99	4	4
neural tube patterning	-0.006	0.15	-9999	-0.43	42	42
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.027	0.051	-9999	-0.39	5	5
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
CSNK1G3	0.014	0	-9999	-10000	0	0
MTSS1	0.01	0.059	-9999	-0.58	5	5
embryonic limb morphogenesis	-0.006	0.15	-9999	-0.43	42	42
SUFU	0.026	0.045	-9999	-0.78	1	1
LGALS3	-0.027	0.14	-9999	-0.5	41	41
catabolic process	0.064	0.064	-9999	-0.49	1	1
GLI3A/CBP	-0.018	0.1	-9999	-0.34	32	32
KIF3A	0.013	0.027	-9999	-0.59	1	1
GLI1	-0.007	0.16	-9999	-0.44	42	42
RAB23	0.013	0.027	-9999	-0.59	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	0.011	0.046	-9999	-0.59	3	3
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.008	0.089	-9999	-0.46	5	5
GNAZ	0.014	0.003	-9999	-10000	0	0
RBBP4	0.013	0.027	-9999	-0.59	1	1
CSNK1G1	0.013	0.022	-9999	-0.49	1	1
PIAS1	0.009	0.053	-9999	-0.59	4	4
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.047	0.034	-9999	-10000	0	0
STK36	0.014	0.027	-9999	-0.59	1	1
Gi family/GNB1/GNG2/GDP	0.03	0.069	-9999	-0.48	3	3
PTCH1	-0.007	0.19	-9999	-0.83	15	15
MIM/GLI1	-0.009	0.17	-9999	-0.59	17	17
CREBBP	-0.018	0.1	-9999	-0.34	32	32
Su(fu)/SIN3/HDAC complex	0.051	0.03	-9999	-0.28	1	1

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.015	0.077	-9999	-0.38	8	8
PDGFB-D/PDGFRB/SLAP	-0.006	0.1	-9999	-0.4	32	32
PDGFB-D/PDGFRB/APS/CBL	-0.005	0.061	-9999	-0.36	14	14
AKT1	0.058	0.037	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.009	0.086	-9999	-0.38	8	8
PIK3CA	0.013	0.027	-9999	-0.59	1	1
FGR	0.001	0.028	-9999	-10000	0	0
mol:Ca2+	0.019	0.041	-9999	-10000	0	0
MYC	0.003	0.18	-9999	-0.8	22	22
SHC1	0.009	0.05	-9999	-0.49	5	5
HRAS/GDP	0.037	0.021	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.003	0.024	-9999	-0.28	1	1
GRB10	0.011	0.044	-9999	-0.56	3	3
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0.019	0.041	-9999	-10000	0	0
PTEN	0.013	0.027	-9999	-0.59	1	1
GRB2	0.013	0.022	-9999	-0.49	1	1
GRB7	-0.031	0.14	-9999	-0.49	42	42
PDGFB-D/PDGFRB/SHP2	0.017	0.028	-9999	-0.34	3	3
PDGFB-D/PDGFRB/GRB10	0.015	0.043	-9999	-0.37	6	6
cell cycle arrest	-0.006	0.1	-9999	-0.39	32	32
HRAS	0.014	0	-9999	-10000	0	0
HIF1A	0.063	0.041	-9999	-0.44	1	1
GAB1	0.006	0.072	-9999	-0.37	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.01	0.074	-9999	-0.37	4	4
PDGFB-D/PDGFRB	0.011	0.029	-9999	-0.29	3	3
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.017	0.028	-9999	-0.34	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.025	0.085	-9999	-0.41	12	12
positive regulation of MAPKKK cascade	0.017	0.028	-9999	-0.34	3	3
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	0.019	0.042	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.014	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.015	0.1	-9999	-0.35	44	44
SHB	0.014	0	-9999	-10000	0	0
BLK	-0.055	0.14	-9999	-0.55	32	32
PTPN2	0.014	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.017	0.028	-9999	-0.34	3	3
BCAR1	0.013	0.027	-9999	-0.59	1	1
VAV2	0.008	0.086	-9999	-0.41	6	6
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.017	0.033	-9999	-0.34	4	4
LCK	-0.053	0.15	-9999	-0.53	40	40
PDGFRB	0.011	0.039	-9999	-0.49	3	3
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.009	0.091	-9999	-0.61	10	10
ABL1	0.008	0.062	-9999	-0.34	2	2
PDGFB-D/PDGFRB/CBL	0.007	0.07	-9999	-0.39	2	2
PTPN1	0.014	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.002	0.088	-9999	-0.49	16	16
cell proliferation	0.007	0.16	-9999	-0.7	22	22
SLA	-0.018	0.13	-9999	-0.54	30	30
actin cytoskeleton reorganization	0.048	0.032	-9999	-10000	0	0
SRC	0.003	0.026	-9999	-10000	0	0
PI3K	-0.005	0.031	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.023	0.092	-9999	-0.68	2	2
SH2B2	0	0.089	-9999	-0.57	12	12
PLCgamma1/SPHK1	0.008	0.088	-9999	-0.39	8	8
LYN	-0.001	0.051	-9999	-0.63	2	2
LRP1	0.014	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
STAT5B	0.014	0	-9999	-10000	0	0
STAT5A	0.001	0.088	-9999	-0.59	11	11
NCK1-2/p130 Cas	0.008	0.031	-9999	-10000	0	0
SPHK1	-0.028	0.15	-9999	-0.54	40	40
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.019	0.042	-9999	-10000	0	0
PLCG1	0.019	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.044	-9999	-0.32	8	8
YES1	-0.002	0.056	-9999	-0.55	4	4
cell migration	-0.004	0.042	-9999	-0.32	8	8
SHC/Grb2/SOS1	0.006	0.041	-9999	-0.46	2	2
SLC9A3R2	0.012	0.031	-9999	-0.49	2	2
SLC9A3R1	0.009	0.053	-9999	-0.59	4	4
NHERF1-2/PDGFRB/PTEN	0.007	0.044	-9999	-0.32	5	5
FYN	0.003	0.026	-9999	-10000	0	0
DOK1	0.032	0.03	-9999	-0.33	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.014	0	-9999	-10000	0	0
RAC1	0.013	0.11	-9999	-0.44	23	23
PRKCD	0.015	0.083	-9999	-0.32	27	27
FER	0.018	0.075	-9999	-0.32	21	21
MAPKKK cascade	-0.004	0.034	-9999	-0.45	2	2
RASA1	0.033	0.023	-9999	-10000	0	0
NCK1	0.013	0.027	-9999	-0.59	1	1
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	0.04	0.027	-9999	-0.3	1	1
PDGFB-D/PDGFRB/SHB	0.017	0.028	-9999	-0.34	3	3
chemotaxis	0.008	0.061	-9999	-0.34	2	2
STAT1-3-5/STAT1-3-5	-0.013	0.052	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.008	0.028	-9999	-0.35	3	3
PTPRJ	0.013	0.022	-9999	-0.49	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.012	0.17	-9999	-1.3	6	6
PLK1	0.05	0.21	-9999	-0.98	9	9
CDKN1B	0.098	0.11	-9999	-10000	0	0
FOXO3	0.064	0.16	-9999	-0.58	9	9
KAT2B	0.022	0.026	-9999	-0.47	1	1
FOXO1/SIRT1	-0.004	0.069	-9999	-0.4	6	6
CAT	0.066	0.16	-9999	-0.81	3	3
CTNNB1	0.014	0	-9999	-10000	0	0
AKT1	0.024	0.017	-9999	-10000	0	0
FOXO1	0.027	0.083	-9999	-0.44	6	6
MAPK10	0.038	0.034	-9999	-0.31	4	4
mol:GTP	0.002	0.002	-9999	-10000	0	0
FOXO4	0.094	0.067	-9999	-0.49	1	1
response to oxidative stress	0.01	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	0.011	0.14	-9999	-0.56	8	8
XPO1	0.015	0.001	-9999	-10000	0	0
EP300	0.011	0.054	-9999	-0.59	4	4
BCL2L11	0.028	0.11	-9999	-1.4	3	3
FOXO1/SKP2	0.025	0.088	-9999	-0.41	11	11
mol:GDP	0.01	0.02	-9999	-10000	0	0
RAN	0.016	0.001	-9999	-10000	0	0
GADD45A	0.079	0.14	-9999	-0.48	12	12
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.043	0.071	-9999	-10000	0	0
MST1	-0.017	0.15	-9999	-0.57	35	35
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.01	0.1	-9999	-0.52	1	1
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.032	0.056	-9999	-0.3	13	13
MAPK9	0.04	0.014	-9999	-10000	0	0
YWHAG	0.001	0.079	-9999	-0.49	13	13
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.009	0.011	-9999	-10000	0	0
SOD2	0.094	0.16	-9999	-0.63	4	4
RBL2	0.083	0.13	-9999	-1.2	1	1
RAL/GDP	0.029	0.017	-9999	-10000	0	0
CHUK	0.023	0.014	-9999	-10000	0	0
Ran/GTP	0.014	0.005	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
RAL/GTP	0.037	0.019	-9999	-10000	0	0
CSNK1G1	0.013	0.022	-9999	-0.49	1	1
FASLG	0.005	0.1	-9999	-10000	0	0
SKP2	0.005	0.071	-9999	-0.55	8	8
USP7	0.016	0.001	-9999	-10000	0	0
IKBKB	0.023	0.014	-9999	-10000	0	0
CCNB1	0.056	0.18	-9999	-0.73	5	5
FOXO1-3a-4/beta catenin	0.12	0.13	-9999	-0.42	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.088	-9999	-0.41	11	11
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.006	0.099	-9999	-0.58	14	14
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.009	-9999	-10000	0	0
ZFAND5	0.097	0.06	-9999	-10000	0	0
SFN	-0.11	0.23	-9999	-0.53	117	117
CDK2	0	0.086	-9999	-0.53	13	13
FOXO3A/14-3-3	0.023	0.093	-9999	-0.43	1	1
CREBBP	0.014	0.013	-9999	-10000	0	0
FBXO32	0.055	0.19	-9999	-0.99	5	5
BCL6	0.085	0.12	-9999	-10000	0	0
RALB	0.015	0.001	-9999	-10000	0	0
RALA	0.015	0.001	-9999	-10000	0	0
YWHAH	-0.009	0.11	-9999	-0.49	24	24

×

Arf6 trafficking 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.062	0.19	-10000	0	-0.55	69	69
CLTC	0.031	0.015	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.016	0.046	-10000	0	-10000	0	0
Dynamin 2/GTP	0.027	0	-10000	0	-10000	0	0
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.025	0.022	-10000	0	-10000	0	0
CPE	0.007	0.07	-10000	0	-0.36	18	18
CTNNB1	0.014	0	-10000	0	-10000	0	0
membrane fusion	0.014	0.048	-10000	0	-10000	0	0
CTNND1	0.035	0	-10000	0	-10000	0	0
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.025	-10000	0	-10000	0	0
TSHR	-0.11	0.17	-10000	0	-0.33	195	195
INS	0.006	0.048	-10000	0	-0.52	4	4
BIN1	0.013	0.027	-10000	0	-0.59	1	1
mol:Choline	0.014	0.048	-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	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.021	0.04	-10000	0	-0.29	4	4
ASAP2/amphiphysin II	-0.001	0.014	-10000	0	-0.32	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.021	0.089	-10000	0	-0.29	13	13
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.047	0.006	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.051	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.012	0.044	-10000	0	-0.28	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.021	0.086	-10000	0	-0.29	6	6
clathrin heavy chain/ACAP1	0.031	0.03	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.014	0	-10000	0	-10000	0	0
exocyst	0.047	0.006	-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	0.035	0	-10000	0	-10000	0	0
NME1	0.02	0	-10000	0	-10000	0	0
clathrin coat assembly	0.031	0.015	-10000	0	-10000	0	0
IL2RA	0.002	0.057	-10000	0	-0.29	1	1
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.036	0.083	-10000	0	-0.34	8	8
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.021	0.071	-10000	0	-0.28	33	33
PLD2	-0.001	0.012	-10000	0	-0.28	1	1
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.028	0.025	-10000	0	-10000	0	0
SDC1	0.011	0.05	-10000	0	-10000	0	0
ARF6/GDP	0.02	0	-10000	0	-10000	0	0
EXOC7	0.013	0.022	-10000	0	-0.49	1	1
E-cadherin/beta catenin	-0.026	0.053	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.014	0.048	-10000	0	-10000	0	0
endocytosis	0.001	0.014	0.32	1	-10000	0	1
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.022	0.071	-10000	0	-0.32	8	8
EXOC3	0.014	0	-10000	0	-10000	0	0
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.028	0	-10000	0	-10000	0	0
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.025	0.055	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.045	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.014	0	-10000	0	-10000	0	0
PTK2	0.014	0	-10000	0	-10000	0	0
CRKL	0.018	0.057	-10000	0	-0.28	15	15
GRB2/SOS1/SHC	-0.003	0.03	-10000	0	-0.28	6	6
HRAS	0.014	0	-10000	0	-10000	0	0
IRS1/Crk	0.018	0.056	-10000	0	-0.29	14	14
IGF-1R heterotetramer/IGF1/PTP1B	-0.012	0.061	-10000	0	-0.33	14	14
AKT1	0.038	0.057	-10000	0	-0.53	1	1
BAD	0.044	0.054	-10000	0	-0.49	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.056	-10000	0	-0.29	14	14
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.018	0.056	-10000	0	-0.29	14	14
RAF1	0.048	0.054	-10000	0	-0.52	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.025	0.055	-10000	0	-0.27	14	14
YWHAZ	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.009	0.061	-10000	0	-0.32	14	14
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
RPS6KB1	0.038	0.057	-10000	0	-0.53	1	1
GNB2L1	0.014	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.041	0.048	-10000	0	-0.44	1	1
PXN	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.014	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.015	-10000	0	-0.34	1	1
HRAS/GTP	-0.01	0.047	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.012	0.055	-10000	0	-0.43	2	2
IGF-1R heterotetramer	0.011	0.026	-10000	0	-0.48	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	0.018	0.057	-10000	0	-0.29	14	14
Crk/p130 Cas/Paxillin	-0.009	0.045	-10000	0	-10000	0	0
IGF1R	0.011	0.026	-10000	0	-0.48	1	1
IGF1	-0.008	0.11	-10000	0	-0.56	20	20
IRS2/Crk	0.025	0.058	-10000	0	-0.28	15	15
PI3K	0.025	0.055	-10000	0	-0.29	1	1
apoptosis	-0.048	0.048	0.42	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.015	0.12	-10000	0	-0.54	14	14
RAF1/14-3-3 E	0.053	0.049	-10000	0	-0.44	1	1
BAD/14-3-3	0.051	0.051	-10000	0	-0.45	1	1
PRKCZ	0.024	0.085	-10000	0	-0.46	3	3
Crk/p130 Cas/Paxillin/FAK1	-0.008	0.038	-10000	0	-0.44	1	1
PTPN1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.024	0.075	-10000	0	-0.4	14	14
BCAR1	0.013	0.027	-10000	0	-0.59	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.015	0.065	-10000	0	-0.4	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.014	0	-10000	0	-10000	0	0
IRS1/NCK2	0.018	0.056	-10000	0	-0.29	14	14
GRB10	0.011	0.044	-10000	0	-0.56	3	3
PTPN11	0.018	0.056	-10000	0	-0.29	14	14
IRS1	0.009	0.061	-10000	0	-0.32	14	14
IRS2	0.017	0.061	-10000	0	-0.3	16	16
IGF-1R heterotetramer/IGF1	0.002	0.085	-10000	0	-0.41	21	21
GRB2	0.013	0.022	-10000	0	-0.49	1	1
PDPK1	0.031	0.059	-10000	0	-0.57	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0
PRKD1	0.031	0.071	-10000	0	-0.37	14	14
SHC1	0.009	0.05	-10000	0	-0.49	5	5

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.017	0.12	-10000	0	-0.41	34	34
regulation of axonogenesis	-0.005	0.069	-10000	0	-10000	0	0
myoblast fusion	-0.004	0.059	0.41	2	-10000	0	2
mol:GTP	-0.01	0.034	-10000	0	-0.23	2	2
regulation of calcium-dependent cell-cell adhesion	-0.027	0.04	0.34	1	-10000	0	1
ARF1/GTP	-0.006	0.022	-10000	0	-10000	0	0
mol:GM1	0.004	0.028	-10000	0	-10000	0	0
mol:Choline	-0.006	0.1	-10000	0	-0.32	45	45
lamellipodium assembly	-0.016	0.055	-10000	0	-0.45	2	2
MAPK3	0.018	0.054	-10000	0	-0.33	2	2
ARF6/GTP/NME1/Tiam1	0.028	0.04	-10000	0	-0.34	1	1
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	0.004	0.059	-10000	0	-0.41	2	2
ARF1/GDP	0.014	0.055	-10000	0	-0.37	2	2
ARF6	0.008	0.02	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.014	0.027	-10000	0	-0.59	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.054	-10000	0	-0.33	2	2
actin filament bundle formation	-0.013	0.054	0.37	2	-10000	0	2
KALRN	-0.018	0.058	-10000	0	-0.32	4	4
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.055	-10000	0	-0.38	2	2
NME1	0.015	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.055	-10000	0	-0.38	2	2
substrate adhesion-dependent cell spreading	-0.01	0.034	-10000	0	-0.23	2	2
cortical actin cytoskeleton organization	-0.016	0.055	-10000	0	-0.45	2	2
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.01	0.034	-10000	0	-0.23	2	2
ARF6/GTP	-0.01	0.034	-10000	0	-0.23	2	2
RhoA/GTP	-0.006	0.022	-10000	0	-10000	0	0
mol:GDP	-0.016	0.054	-10000	0	-0.42	2	2
ARF6/GTP/RAB11FIP3/RAB11A	-0.004	0.017	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	-0.019	0.11	-10000	0	-0.38	44	44
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.016	0.055	-10000	0	-0.45	2	2
ruffle organization	0.005	0.069	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.034	-10000	0	-0.23	2	2
PLD2	0.015	0.033	-10000	0	-0.4	1	1
PIP5K1A	0.005	0.069	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.006	0.1	-10000	0	-0.32	45	45
Rac1/GTP	-0.016	0.055	-10000	0	-0.45	2	2

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.016	-10000	0	-0.34	1	1
BAD/BCL-XL/YWHAZ	0.036	0.012	-10000	0	-10000	0	0
CDKN1B	0.04	0.009	-10000	0	-10000	0	0
CDKN1A	0.008	0.089	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
FOXO3	0.04	0.009	-10000	0	-10000	0	0
AKT1	0	0.007	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
AKT3	0.013	0.061	-10000	0	-0.55	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.04	0.016	-10000	0	-0.28	1	1
AKT1/ASK1	0.034	0.038	-10000	0	-0.39	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.014	0	-10000	0	-10000	0	0
RAF1	0.014	0	-10000	0	-10000	0	0
JNK cascade	0.004	0.033	0.38	1	-10000	0	1
TSC1	0.04	0.009	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
AKT1/RAF1	0.04	0.009	-10000	0	-10000	0	0
EP300	0.009	0.053	-10000	0	-0.59	4	4
mol:GDP	0.033	0.009	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.04	0.009	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0.02	-10000	0	-0.3	2	2
MAP3K5	0.006	0.07	-10000	0	-0.59	7	7
MAPKAP1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.013	0.059	0.27	1	-10000	0	1
YWHAH	-0.009	0.11	-10000	0	-0.49	24	24
AKT1S1	0.04	0.009	-10000	0	-10000	0	0
CASP9	0.04	0.014	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.047	0.008	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.022	-10000	0	-0.36	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0
SRC	0.014	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.027	0.073	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.003	-10000	0	-10000	0	0
CHUK	0.04	0.009	-10000	0	-10000	0	0
BAD/BCL-XL	0.054	0.013	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	0.023	-10000	0	-0.35	2	2
FOXO1-3a-4/14-3-3 family	0.03	0.063	-10000	0	-0.29	1	1
PDPK1	0.012	0.038	-10000	0	-0.59	2	2
MDM2	0.039	0.018	-10000	0	-10000	0	0
MAPKKK cascade	-0.039	0.008	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.05	0.035	-10000	0	-0.37	2	2
TSC1/TSC2	0.047	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.034	-10000	0	-0.35	2	2
glucose import	-0.011	0.11	-10000	0	-0.29	71	71
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.011	0.11	-10000	0	-0.29	71	71
GSK3A	0.04	0.009	-10000	0	-10000	0	0
FOXO1	0.038	0.024	-10000	0	-10000	0	0
GSK3B	0.04	0.021	-10000	0	-0.41	1	1
SFN	-0.11	0.23	-10000	0	-0.53	117	117
G1/S transition of mitotic cell cycle	0.046	0.02	-10000	0	-0.39	1	1
p27Kip1/14-3-3 family	0.007	0.085	-10000	0	-0.39	3	3
PRKACA	0.014	0	-10000	0	-10000	0	0
KPNA1	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
YWHAG	0.001	0.079	-10000	0	-0.49	13	13
RHEB	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.014	0	-9999	-10000	0	0
SMAD2	0.016	0.018	-9999	-0.25	1	1
SMAD3	0.044	0.018	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0.01	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.014	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.012	0.035	-9999	-0.54	2	2
SMAD2/SMAD4	0.023	0.015	-9999	-10000	0	0
MAP3K1	0.007	0.059	-9999	-0.49	7	7
TRAP-1/SMAD4	-0.014	0.076	-9999	-0.43	17	17
MAPK3	0.014	0	-9999	-10000	0	0
MAPK1	0.014	0	-9999	-10000	0	0
NUP214	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
CTDSP2	0.01	0.044	-9999	-0.49	4	4
CTDSPL	0.013	0.027	-9999	-0.59	1	1
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	-0.006	0.11	-9999	-0.59	17	17
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.012	0.031	-9999	-0.49	2	2
PIAS4	0.014	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.035	-9999	-0.47	1	1
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.003	0.035	-9999	-0.36	5	5
RELB	0.009	0.052	-9999	-0.51	5	5
NFKB2	0.011	0.044	-9999	-0.56	3	3
NF kappa B2 p52/RelB	-0.005	0.043	-9999	-0.36	7	7
regulation of B cell activation	-0.005	0.043	-9999	-0.36	7	7

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.009	0.053	-10000	0	-0.59	4	4
mol:PIP3	0	0.018	0.29	1	-0.3	1	2
FRAP1	0.016	0.01	-10000	0	-10000	0	0
AKT1	0.03	0.026	0.23	1	-0.45	1	2
INSR	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.035	-10000	0	-0.35	5	5
mol:GTP	-0.001	0.018	-10000	0	-0.37	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.007	-10000	0	-10000	0	0
TSC2	0.014	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.016	-10000	0	-0.34	1	1
TSC1	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.018	0.001	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.017	0.18	1	-0.28	1	2
MAP3K5	0.006	0.046	-10000	0	-0.39	7	7
PIK3R1	0.014	0	-10000	0	-10000	0	0
apoptosis	0.006	0.046	-10000	0	-0.38	7	7
mol:LY294002	0	0	0.001	1	-10000	0	1
EIF4B	0.036	0.016	-10000	0	-0.24	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.013	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.002	0.016	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.026	0.015	-10000	0	-0.31	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.034	0.014	0.17	1	-0.2	1	2
FKBP1A	0.014	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.016	-10000	0	-0.33	1	1
mol:Amino Acids	0	0	0.001	1	-10000	0	1
FKBP12/Rapamycin	0.011	0.001	-10000	0	-10000	0	0
PDPK1	-0.001	0.03	0.24	1	-0.42	2	3
EIF4E	0.014	0	-10000	0	-10000	0	0
ASK1/PP5C	0.015	0.073	-10000	0	-0.6	7	7
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.019	-10000	0	-0.4	1	1
tumor necrosis factor receptor activity	0	0	-10000	0	-0.001	1	1
RPS6	0.013	0.022	-10000	0	-0.49	1	1
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.009	0.001	-10000	0	-10000	0	0
INS	-0.005	0.056	-10000	0	-0.57	5	5
PTEN	0.012	0.027	-10000	0	-0.59	1	1
PDK2	-0.001	0.021	0.24	1	-0.28	2	3
EIF4EBP1	-0.003	0.13	-10000	0	-1.1	7	7
PIK3CA	0.013	0.027	-10000	0	-0.59	1	1
PPP2R5D	0.023	0.009	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.032	-10000	0	-0.31	5	5
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.003	1	2
EEF2	0.016	0.032	-10000	0	-0.31	5	5
eIF4E/4E-BP1	0.005	0.12	-10000	0	-1	7	7

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.053	-9999	-0.59	4	4
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.032	0.016	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.002	0.021	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.031	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0	-9999	-10000	0	0
SUMO1/HDAC1	0.031	0.028	-9999	-0.29	4	4
RANGAP1	0.014	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.004	0.035	-9999	-0.32	5	5
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	0	-9999	-10000	0	0
Ran/GTP	0.029	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.012	0.031	-9999	-0.49	2	2
UBE2I	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.036	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.013	0.027	-9999	-0.59	1	1
PIAS1	0.009	0.053	-9999	-0.59	4	4
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.009	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.022	0.005	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.001	-9999	-10000	0	0
CLTB	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-10000	0	0
CD4	0.008	0.056	-9999	-0.51	6	6
CLTA	0.014	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.012	0.016	-9999	-0.35	1	1
mol:PI-4-5-P2	0	0.008	-9999	-0.19	1	1
ARF1/GTP	0	0.004	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0.011	-9999	-0.22	1	1
mol:Choline	0	0.009	-9999	-0.2	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	0	0.009	-9999	-0.2	1	1
ARF1/GDP	-0.001	0.011	-9999	-0.24	1	1
AP2M1	0.014	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.018	0	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.027	0.012	-9999	-0.24	1	1
ARFIP2	0.012	0	-9999	-10000	0	0
COPA	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.028	0.003	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.002	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	0.007	-9999	-10000	0	0
ARF1/GDP/Membrin	0.02	0.004	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.001	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.001	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.037	0.017	-9999	-0.21	1	1
PLD2	0	0.009	-9999	-0.2	1	1
ARF-GAP1/v-SNARE	0.012	0.016	-9999	-0.35	1	1
PIP5K1A	0	0.009	-9999	-0.19	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.004	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.009	-9999	-0.2	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.012	0.016	-9999	-0.35	1	1
GOSR2	0	0.004	-9999	-10000	0	0
USO1	0	0.004	-9999	-10000	0	0
GBF1	0	0.004	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.003	0.032	-9999	-0.29	6	6

pid_entity	TCGA.WY.A85E	TCGA.WY.A85D	TCGA.WY.A85C	TCGA.WY.A85B
109_MAP3K5	0.059	-0.21	0.059	-0.21
47_PPARGC1A	0.014	0.014	0.014	0.014
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	0.014	0.014	0.014
131_RELN/VLDLR	0	0	-0.32	0
30_TGFB1/TGF beta receptor Type II	0.014	0.014	0.014	0.014
84_STAT5B	0.011	0.049	0.049	0.049
84_STAT5A	0.011	0.049	0.049	0.049