PARADIGM pathway analysis of mRNASeq expression and copy number data - Colorectal Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	164
Reelin signaling pathway	157
Ephrin A reverse signaling	97
Lissencephaly gene (LIS1) in neuronal migration and development	91
Glypican 1 network	83
IL4-mediated signaling events	76
BCR signaling pathway	72
Signaling events mediated by Stem cell factor receptor (c-Kit)	68
Fc-epsilon receptor I signaling in mast cells	65
FOXA2 and FOXA3 transcription factor networks	61

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
TCGA08_retinoblastoma	0.2632	164	1318	8	-0.091	0.083	1000	-1000	-0.007	-1000
Reelin signaling pathway	0.2520	157	8814	56	-0.35	0.075	1000	-1000	-0.056	-1000
Ephrin A reverse signaling	0.1557	97	681	7	-0.056	0	1000	-1000	-0.017	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1461	91	4933	54	-0.3	0.037	1000	-1000	-0.053	-1000
Glypican 1 network	0.1332	83	4016	48	-0.19	0.053	1000	-1000	-0.033	-1000
IL4-mediated signaling events	0.1220	76	6979	91	-0.79	0.56	1000	-1000	-0.18	-1000
BCR signaling pathway	0.1156	72	7194	99	-0.19	0.03	1000	-1000	-0.061	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1091	68	5349	78	-0.19	0.073	1000	-1000	-0.053	-1000
Fc-epsilon receptor I signaling in mast cells	0.1043	65	6334	97	-0.14	0.05	1000	-1000	-0.067	-1000
FOXA2 and FOXA3 transcription factor networks	0.0979	61	2830	46	-0.59	0.031	1000	-1000	-0.15	-1000
Signaling events regulated by Ret tyrosine kinase	0.0915	57	4681	82	-0.12	0.035	1000	-1000	-0.063	-1000
Syndecan-1-mediated signaling events	0.0835	52	1786	34	-0.42	0.029	1000	-1000	-0.046	-1000
p75(NTR)-mediated signaling	0.0835	52	6524	125	-0.46	0.071	1000	-1000	-0.084	-1000
Signaling events mediated by the Hedgehog family	0.0819	51	2660	52	-0.059	0.059	1000	-1000	-0.036	-1000
HIF-1-alpha transcription factor network	0.0819	51	3895	76	-0.56	0.036	1000	-1000	-0.17	-1000
BMP receptor signaling	0.0803	50	4101	81	-0.18	0.052	1000	-1000	-0.048	-1000
Visual signal transduction: Rods	0.0787	49	2597	52	-0.19	0.035	1000	-1000	-0.041	-1000
Endothelins	0.0770	48	4659	96	-0.22	0.061	1000	-1000	-0.059	-1000
Syndecan-2-mediated signaling events	0.0754	47	3271	69	-0.23	0.046	1000	-1000	-0.036	-1000
JNK signaling in the CD4+ TCR pathway	0.0690	43	735	17	-0.13	0.041	1000	-1000	-0.033	-1000
Visual signal transduction: Cones	0.0658	41	1572	38	-0.11	0.038	1000	-1000	-0.02	-1000
Plasma membrane estrogen receptor signaling	0.0642	40	3460	86	-0.23	0.079	1000	-1000	-0.058	-1000
LPA receptor mediated events	0.0610	38	3936	102	-0.17	0.036	1000	-1000	-0.058	-1000
Ras signaling in the CD4+ TCR pathway	0.0610	38	657	17	-0.062	0.049	1000	-1000	-0.03	-1000
TCR signaling in naïve CD8+ T cells	0.0594	37	3487	93	-0.037	0.04	1000	-1000	-0.049	-1000
IGF1 pathway	0.0594	37	2123	57	-0.065	0.054	1000	-1000	-0.049	-1000
Wnt signaling	0.0578	36	255	7	-0.069	0.024	1000	-1000	-0.021	-1000
Effects of Botulinum toxin	0.0562	35	935	26	-0.07	0.049	1000	-1000	-0.016	-1000
IL23-mediated signaling events	0.0562	35	2101	60	-0.27	0.033	1000	-1000	-0.13	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0562	35	3104	88	-0.14	0.061	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0546	34	408	12	-0.097	0.007	1000	-1000	-0.028	-1000
Osteopontin-mediated events	0.0546	34	1308	38	-0.17	0.04	1000	-1000	-0.05	-1000
amb2 Integrin signaling	0.0514	32	2626	82	-0.095	0.037	1000	-1000	-0.05	-1000
Canonical Wnt signaling pathway	0.0514	32	1661	51	-0.28	0.14	1000	-1000	-0.054	-1000
Nongenotropic Androgen signaling	0.0514	32	1712	52	-0.12	0.063	1000	-1000	-0.04	-1000
Presenilin action in Notch and Wnt signaling	0.0498	31	1915	61	-0.28	0.14	1000	-1000	-0.043	-1000
IL1-mediated signaling events	0.0498	31	1978	62	-0.12	0.063	1000	-1000	-0.044	-1000
Ephrin B reverse signaling	0.0498	31	1504	48	-0.07	0.031	1000	-1000	-0.027	-1000
Signaling events mediated by PRL	0.0498	31	1087	34	-0.062	0.086	1000	-1000	-0.049	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0465	29	1525	52	-0.18	0.061	1000	-1000	-0.053	-1000
TCGA08_p53	0.0465	29	208	7	-0.054	0.028	1000	-1000	-0.007	-1000
Calcium signaling in the CD4+ TCR pathway	0.0465	29	900	31	-0.27	0.028	1000	-1000	-0.053	-1000
Thromboxane A2 receptor signaling	0.0449	28	2968	105	-0.18	0.067	1000	-1000	-0.043	-1000
EPHB forward signaling	0.0449	28	2437	85	-0.071	0.087	1000	-1000	-0.071	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0449	28	3366	120	-0.097	0.088	1000	-1000	-0.053	-1000
Signaling mediated by p38-alpha and p38-beta	0.0433	27	1224	44	-0.035	0.029	1000	-1000	-0.041	-1000
Arf6 signaling events	0.0417	26	1615	62	-0.12	0.062	1000	-1000	-0.04	-1000
Glucocorticoid receptor regulatory network	0.0417	26	3013	114	-0.32	0.19	1000	-1000	-0.062	-1000
S1P5 pathway	0.0417	26	454	17	-0.12	0.052	1000	-1000	-0.023	-1000
Syndecan-3-mediated signaling events	0.0417	26	910	35	-0.23	0.071	1000	-1000	-0.032	-1000
EGFR-dependent Endothelin signaling events	0.0417	26	549	21	-0.06	0.04	1000	-1000	-0.046	-1000
PDGFR-beta signaling pathway	0.0417	26	2601	97	-0.14	0.09	1000	-1000	-0.058	-1000
Syndecan-4-mediated signaling events	0.0401	25	1740	67	-0.23	0.04	1000	-1000	-0.051	-1000
S1P4 pathway	0.0401	25	644	25	-0.12	0.043	1000	-1000	-0.035	-1000
IL12-mediated signaling events	0.0385	24	2121	87	-0.1	0.051	1000	-1000	-0.1	-1000
Nectin adhesion pathway	0.0369	23	1452	63	-0.4	0.076	1000	-1000	-0.06	-1000
HIF-2-alpha transcription factor network	0.0369	23	1015	43	-0.33	0.16	1000	-1000	-0.085	-1000
Integrins in angiogenesis	0.0353	22	1880	84	-0.18	0.065	1000	-1000	-0.054	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0353	22	1528	68	-0.28	0.038	1000	-1000	-0.12	-1000
Caspase cascade in apoptosis	0.0337	21	1565	74	-0.085	0.064	1000	-1000	-0.041	-1000
Noncanonical Wnt signaling pathway	0.0337	21	546	26	-0.069	0.027	1000	-1000	-0.047	-1000
a4b1 and a4b7 Integrin signaling	0.0337	21	107	5	0.013	0.03	1000	-1000	0.001	-1000
Regulation of Androgen receptor activity	0.0321	20	1429	70	-0.21	0.06	1000	-1000	-0.064	-1000
Signaling events mediated by PTP1B	0.0305	19	1461	76	-0.19	0.047	1000	-1000	-0.046	-1000
Ceramide signaling pathway	0.0305	19	1510	76	-0.062	0.07	1000	-1000	-0.04	-1000
S1P3 pathway	0.0305	19	827	42	-0.11	0.046	1000	-1000	-0.045	-1000
Signaling events mediated by HDAC Class III	0.0289	18	757	40	-0.13	0.052	1000	-1000	-0.02	-1000
S1P1 pathway	0.0289	18	664	36	-0.12	0.044	1000	-1000	-0.052	-1000
FAS signaling pathway (CD95)	0.0289	18	851	47	-0.03	0.044	1000	-1000	-0.043	-1000
Regulation of p38-alpha and p38-beta	0.0289	18	997	54	-0.09	0.054	1000	-1000	-0.051	-1000
Glypican 2 network	0.0289	18	75	4	0.013	0.025	1000	-1000	-0.001	-1000
Aurora B signaling	0.0289	18	1208	67	-0.41	0.095	1000	-1000	-0.032	-1000
Coregulation of Androgen receptor activity	0.0273	17	1362	76	-0.19	0.064	1000	-1000	-0.022	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0257	16	544	34	-0.027	0.064	1000	-1000	-0.031	-1000
Class I PI3K signaling events	0.0257	16	1179	73	-0.09	0.044	1000	-1000	-0.044	-1000
ErbB2/ErbB3 signaling events	0.0241	15	980	65	-0.046	0.04	1000	-1000	-0.054	-1000
Regulation of nuclear SMAD2/3 signaling	0.0241	15	2089	136	-0.44	0.068	1000	-1000	-0.047	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0241	15	447	28	-0.12	0.044	1000	-1000	-0.03	-1000
Cellular roles of Anthrax toxin	0.0241	15	613	39	-0.048	0.031	1000	-1000	-0.02	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0241	15	578	37	-0.15	0.06	1000	-1000	-0.04	-1000
VEGFR1 specific signals	0.0241	15	880	56	-0.013	0.093	1000	-1000	-0.052	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0241	15	525	33	-0.061	0.066	1000	-1000	-0.033	-1000
ErbB4 signaling events	0.0225	14	976	69	-0.16	0.08	1000	-1000	-0.051	-1000
PLK1 signaling events	0.0225	14	1247	85	-0.01	0.06	1000	-1000	-0.038	-1000
Retinoic acid receptors-mediated signaling	0.0225	14	813	58	-0.15	0.051	1000	-1000	-0.038	-1000
IL6-mediated signaling events	0.0225	14	1123	75	-0.059	0.059	1000	-1000	-0.082	-1000
Class I PI3K signaling events mediated by Akt	0.0209	13	938	68	-0.053	0.064	1000	-1000	-0.037	-1000
Signaling mediated by p38-gamma and p38-delta	0.0209	13	200	15	-0.058	0.027	1000	-1000	-0.037	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0193	12	1069	83	-0.13	0.07	1000	-1000	-0.043	-1000
FoxO family signaling	0.0193	12	787	64	-0.056	0.065	1000	-1000	-0.072	-1000
Arf6 downstream pathway	0.0177	11	506	43	-0.029	0.043	1000	-1000	-0.026	-1000
Insulin-mediated glucose transport	0.0177	11	353	32	-0.14	0.045	1000	-1000	-0.026	-1000
PDGFR-alpha signaling pathway	0.0177	11	516	44	-0.013	0.064	1000	-1000	-0.042	-1000
Arf6 trafficking events	0.0177	11	795	71	-0.048	0.049	1000	-1000	-0.029	-1000
ceramide signaling pathway	0.0161	10	502	49	0	0.045	1000	-1000	-0.046	-1000
FOXM1 transcription factor network	0.0161	10	534	51	-0.096	0.089	1000	-1000	-0.14	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0144	9	805	85	-0.035	0.065	1000	-1000	-0.05	-1000
Hedgehog signaling events mediated by Gli proteins	0.0144	9	589	65	-0.12	0.05	1000	-1000	-0.042	-1000
EPO signaling pathway	0.0144	9	511	55	-0.004	0.065	1000	-1000	-0.049	-1000
IFN-gamma pathway	0.0144	9	659	68	-0.031	0.04	1000	-1000	-0.06	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0144	9	410	45	-0.009	0.073	1000	-1000	-0.053	-1000
IL27-mediated signaling events	0.0144	9	501	51	-0.064	0.042	1000	-1000	-0.052	-1000
TCGA08_rtk_signaling	0.0144	9	238	26	-0.031	0.062	1000	-1000	-0.021	-1000
Regulation of Telomerase	0.0144	9	1017	102	-0.2	0.065	1000	-1000	-0.08	-1000
mTOR signaling pathway	0.0128	8	458	53	-0.067	0.038	1000	-1000	-0.04	-1000
Rapid glucocorticoid signaling	0.0128	8	164	20	-0.016	0.026	1000	-1000	-0.007	-1000
IL2 signaling events mediated by PI3K	0.0112	7	455	58	-0.014	0.046	1000	-1000	-0.05	-1000
Signaling events mediated by HDAC Class II	0.0096	6	514	75	-0.026	0.07	1000	-1000	-0.036	-1000
Aurora A signaling	0.0096	6	406	60	-0.086	0.076	1000	-1000	-0.026	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0096	6	448	74	-0.062	0.065	1000	-1000	-0.068	-1000
E-cadherin signaling in the nascent adherens junction	0.0096	6	520	76	-0.011	0.093	1000	-1000	-0.071	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0080	5	648	125	-0.01	0.098	1000	-1000	-0.06	-1000
Class IB PI3K non-lipid kinase events	0.0080	5	15	3	-0.024	0.024	1000	-1000	-0.001	-1000
Arf1 pathway	0.0080	5	272	54	-0.001	0.046	1000	-1000	-0.024	-1000
TRAIL signaling pathway	0.0064	4	212	48	-0.011	0.059	1000	-1000	-0.041	-1000
Paxillin-dependent events mediated by a4b1	0.0064	4	173	36	-0.049	0.051	1000	-1000	-0.042	-1000
Insulin Pathway	0.0064	4	301	74	-0.026	0.085	1000	-1000	-0.054	-1000
p38 MAPK signaling pathway	0.0064	4	200	44	-0.013	0.058	1000	-1000	-0.035	-1000
PLK2 and PLK4 events	0.0048	3	10	3	0.01	0.027	1000	-1000	-0.019	-1000
IL2 signaling events mediated by STAT5	0.0048	3	81	22	0.006	0.042	1000	-1000	-0.044	-1000
Canonical NF-kappaB pathway	0.0032	2	96	39	0	0.06	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class I	0.0032	2	231	104	-0.054	0.066	1000	-1000	-0.036	-1000
Circadian rhythm pathway	0.0016	1	26	22	-0.01	0.065	1000	-1000	-0.037	-1000
Aurora C signaling	0.0016	1	9	7	0	0.041	1000	-1000	-0.016	-1000
Atypical NF-kappaB pathway	0.0016	1	35	31	0	0.057	1000	-1000	-0.026	-1000
E-cadherin signaling in keratinocytes	0.0016	1	54	43	-0.047	0.086	1000	-1000	-0.039	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	17	23	0.013	0.04	1000	-1000	-0.025	-1000
BARD1 signaling events	0.0000	0	47	57	-0.056	0.078	1000	-1000	-0.053	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	17	27	0	0.052	1000	-1000	-0.039	-1000
E-cadherin signaling events	0.0000	0	2	5	0.027	0.054	1000	-1000	0.002	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.076	1000	-1000	-0.002	-1000
Total	NA	3348	193030	7203	-16	8	131000	-131000	-6.2	-131000

TCGA08_retinoblastoma

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
CDKN2B	-0.091	0.17	-10000	0	-0.33	206	206
CDKN2C	0.033	0.026	-10000	0	-10000	0	0
CDKN2A	-0.065	0.19	0.34	2	-0.46	115	117
CCND2	0.07	0.092	0.19	207	-10000	0	207
RB1	-0.056	0.1	0.28	9	-0.2	173	182
CDK4	0.076	0.097	0.2	202	-0.14	1	203
CDK6	0.083	0.1	0.21	218	-10000	0	218
G1/S progression	0.062	0.1	0.2	175	-0.28	10	185

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.038	0.018	-10000	0	-0.32	1	1
VLDLR	-0.003	0.1	-10000	0	-0.36	47	47
CRKL	0.027	0.006	-10000	0	-10000	0	0
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
ITGA3	0.027	0.016	-10000	0	-0.36	1	1
RELN/VLDLR/Fyn	-0.084	0.15	-10000	0	-0.24	278	278
MAPK8IP1/MKK7/MAP3K11/JNK1	0.075	0.035	-10000	0	-0.51	1	1
AKT1	-0.099	0.13	-10000	0	-0.33	78	78
MAP2K7	0.027	0.016	-10000	0	-0.36	1	1
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1
DAB1	-0.036	0.15	-10000	0	-0.45	71	71
RELN/LRP8/DAB1	-0.26	0.17	-10000	0	-0.33	505	505
LRPAP1/LRP8	-0.21	0.17	0.26	1	-0.32	423	424
RELN/LRP8/DAB1/Fyn	-0.25	0.16	-10000	0	-0.33	440	440
DAB1/alpha3/beta1 Integrin	-0.24	0.17	-10000	0	-0.4	248	248
long-term memory	-0.35	0.21	-10000	0	-0.48	381	381
DAB1/LIS1	-0.24	0.17	-10000	0	-0.41	255	255
DAB1/CRLK/C3G	-0.24	0.17	-10000	0	-0.4	252	252
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
DAB1/NCK2	-0.25	0.18	-10000	0	-0.41	255	255
ARHGEF2	0.027	0.004	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.085	0.16	-10000	0	-0.36	157	157
CDK5R1	0.026	0.019	-10000	0	-0.44	1	1
RELN	-0.16	0.19	-10000	0	-0.36	283	283
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.26	0.17	0.25	1	-0.34	482	483
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.29	0.19	-10000	0	-0.38	457	457
MAPK8	0.027	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.1	0.15	-10000	0	-0.24	314	314
ITGB1	0.028	0.002	-10000	0	-10000	0	0
MAP1B	-0.26	0.17	-10000	0	-0.42	266	266
RELN/LRP8	-0.26	0.17	0.25	1	-0.34	485	486
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.32	0.2	-10000	0	-0.4	475	475
PI3K	0.039	0.015	-10000	0	-0.25	1	1
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.04	0.014	-10000	0	-0.25	1	1
RAP1A	-0.24	0.15	0.32	2	-0.39	247	249
PAFAH1B1	0.023	0.01	-10000	0	-10000	0	0
MAPK8IP1	0.026	0.025	-10000	0	-0.4	2	2
CRLK/C3G	0.038	0.015	-10000	0	-0.25	1	1
GRIN2B	-0.13	0.22	0.36	1	-0.44	201	202
NCK2	0.028	0.001	-10000	0	-10000	0	0
neuron differentiation	-0.13	0.12	0.23	1	-0.26	222	223
neuron adhesion	-0.23	0.15	0.3	3	-0.38	233	236
LRP8	-0.3	0.22	0.36	1	-0.44	424	425
GSK3B	-0.097	0.12	-10000	0	-0.32	75	75
RELN/VLDLR/DAB1/Fyn	-0.092	0.15	-10000	0	-0.32	98	98
MAP3K11	0.026	0.016	-10000	0	-0.36	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.14	-10000	0	-0.29	131	131
CDK5	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.054	0.17	0.83	8	-0.32	124	132
neuron migration	-0.23	0.16	0.27	4	-0.4	233	237
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.12	-10000	0	-0.26	219	219
RELN/VLDLR	-0.24	0.18	0.25	1	-0.34	418	419

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.03	0.11	-10000	0	-0.22	149	149
EFNA5	-0.056	0.16	-10000	0	-0.36	130	130
FYN	-0.045	0.091	0.18	1	-0.22	74	75
neuron projection morphogenesis	-0.03	0.11	-10000	0	-0.22	149	149
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.03	0.11	-10000	0	-0.22	149	149
EPHA5	-0.012	0.081	-10000	0	-0.36	29	29

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.026	0.007	-10000	0	-10000	0	0
VLDLR	-0.003	0.1	-10000	0	-0.36	47	47
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
NUDC	0.026	0.007	-10000	0	-10000	0	0
RELN/LRP8	-0.26	0.17	0.25	1	-0.34	485	486
CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
KATNA1	0.027	0.004	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.24	0.16	0.18	9	-0.33	405	414
IQGAP1/CaM	0.037	0.013	-10000	0	-10000	0	0
DAB1	-0.036	0.15	-10000	0	-0.45	71	71
IQGAP1	0.027	0.006	-10000	0	-10000	0	0
PLA2G7	0.024	0.038	-10000	0	-0.36	6	6
CALM1	0.026	0.007	-10000	0	-10000	0	0
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	-0.21	0.17	0.26	1	-0.32	423	424
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.016	-10000	0	-0.36	1	1
CDK5R1	0.026	0.019	-10000	0	-0.44	1	1
LIS1/Poliovirus Protein 3A	0.007	0.005	-10000	0	-10000	0	0
CDK5R2	-0.02	0.12	-10000	0	-0.37	63	63
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.12	0.16	-10000	0	-0.26	314	314
YWHAE	0.023	0.01	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.2	0.15	0.32	6	-0.35	226	232
MAP1B	0.001	0.032	-10000	0	-0.24	11	11
RAC1	0.01	0.007	-10000	0	-10000	0	0
p35/CDK5	-0.21	0.14	0.18	2	-0.37	197	199
RELN	-0.16	0.19	-10000	0	-0.36	283	283
PAFAH/LIS1	0.02	0.026	-10000	0	-0.2	6	6
LIS1/CLIP170	0.022	0.017	-10000	0	-0.21	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.17	0.12	-10000	0	-0.3	178	178
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.097	0.15	-10000	0	-0.37	89	89
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.22	0.15	0.28	7	-0.36	251	258
LIS1/IQGAP1	0.022	0.014	-10000	0	-10000	0	0
RHOA	0.01	0.007	-10000	0	-10000	0	0
PAFAH1B1	0.01	0.006	-10000	0	-10000	0	0
PAFAH1B3	0.019	0.062	-10000	0	-0.44	11	11
PAFAH1B2	0.027	0.005	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.013	0.039	-10000	0	-0.23	3	3
NDEL1/Katanin 60/Dynein heavy chain	-0.2	0.15	0.32	5	-0.35	224	229
LRP8	-0.3	0.22	0.36	1	-0.44	424	425
NDEL1/Katanin 60	-0.21	0.15	0.32	5	-0.36	227	232
P39/CDK5	-0.23	0.15	0.18	2	-0.39	235	237
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0.014	-10000	0	-10000	0	0
CDK5	-0.23	0.14	0.17	3	-0.39	203	206
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0.014	-10000	0	-0.18	1	1
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.085	0.14	-10000	0	-0.32	85	85
RELN/VLDLR	-0.24	0.18	0.25	1	-0.34	418	419
CDC42	0.01	0.016	-10000	0	-0.35	1	1

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.029	0.069	-10000	0	-0.21	38	38
fibroblast growth factor receptor signaling pathway	0.029	0.069	-10000	0	-0.21	38	38
LAMA1	-0.054	0.15	-10000	0	-0.36	121	121
PRNP	0.021	0.024	-10000	0	-0.36	2	2
GPC1/SLIT2	-0.044	0.13	-10000	0	-0.25	176	176
SMAD2	0.011	0.022	0.18	4	-0.24	1	5
GPC1/PrPc/Cu2+	0.029	0.025	-10000	0	-0.22	4	4
GPC1/Laminin alpha1	-0.026	0.12	-10000	0	-0.25	123	123
TDGF1	-0.19	0.24	0.36	1	-0.44	290	291
CRIPTO/GPC1	-0.13	0.18	0.26	1	-0.32	291	292
APP/GPC1	0.037	0.024	-10000	0	-0.27	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.12	0.14	0.2	1	-0.26	289	290
FLT1	0.021	0.012	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.053	0.023	-10000	0	-0.23	3	3
SERPINC1	0.003	0.061	-10000	0	-0.44	10	10
FYN	-0.12	0.14	0.2	1	-0.27	288	289
FGR	-0.12	0.14	0.2	1	-0.27	291	292
positive regulation of MAPKKK cascade	-0.044	0.12	0.21	33	-0.31	45	78
SLIT2	-0.084	0.17	-10000	0	-0.36	174	174
GPC1/NRG	0.004	0.085	-10000	0	-0.25	58	58
NRG1	-0.015	0.11	-10000	0	-0.36	56	56
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.041	0.031	0.25	1	-0.24	2	3
LYN	-0.11	0.14	0.2	1	-0.27	260	261
mol:Spermine	0.006	0.017	-10000	0	-0.28	2	2
cell growth	0.029	0.069	-10000	0	-0.21	38	38
BMP signaling pathway	-0.026	0.025	0.4	2	-10000	0	2
SRC	-0.063	0.11	0.2	1	-0.27	125	126
TGFBR1	0.027	0.016	-10000	0	-0.36	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.071	0.17	-10000	0	-0.36	151	151
GPC1	0.026	0.025	-10000	0	-0.4	2	2
TGFBR1 (dimer)	0.027	0.016	-10000	0	-0.36	1	1
VEGFA	0.028	0.019	0.36	2	-10000	0	2
BLK	-0.18	0.16	0.2	1	-0.29	378	379
HCK	-0.066	0.11	0.2	1	-0.27	130	131
FGF2	0	0.099	-10000	0	-0.36	43	43
FGFR1	0.021	0.032	-10000	0	-0.36	4	4
VEGFR1 homodimer	0.021	0.012	-10000	0	-10000	0	0
TGFBR2	0.027	0.003	-10000	0	-10000	0	0
cell death	0.037	0.024	-10000	0	-0.27	3	3
ATIII/GPC1	0.03	0.049	-10000	0	-0.31	12	12
PLA2G2A/GPC1	-0.036	0.13	-10000	0	-0.26	153	153
LCK	-0.12	0.14	0.2	1	-0.27	297	298
neuron differentiation	0.004	0.085	-10000	0	-0.25	58	58
PrPc/Cu2+	0.016	0.017	-10000	0	-0.25	2	2
APP	0.026	0.017	-10000	0	-0.36	1	1
TGFBR2 (dimer)	0.027	0.003	-10000	0	-10000	0	0

×

IL4-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
BCL2L1	-0.45	0.49	-10000	0	-1.2	109	109
STAT6 (cleaved dimer)	-0.55	0.51	-10000	0	-1.2	178	178
IGHG1	-0.16	0.16	-10000	0	-10000	0	0
IGHG3	-0.49	0.46	-10000	0	-1.1	155	155
AKT1	-0.27	0.29	-10000	0	-0.78	76	76
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.21	0.24	-10000	0	-0.86	29	29
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.26	0.28	-10000	0	-1	33	33
THY1	-0.52	0.48	-10000	0	-1.2	129	129
MYB	0.026	0.016	-10000	0	-0.36	1	1
HMGA1	0.027	0.023	0.36	1	-0.44	1	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.36	0.35	-10000	0	-0.84	148	148
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.26	0.28	-10000	0	-1	31	31
SP1	0.027	0.02	-10000	0	-10000	0	0
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
SOCS5	0.045	0.026	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.55	0.51	-10000	0	-1.2	170	170
SOCS1	-0.37	0.31	-10000	0	-0.77	127	127
SOCS3	-0.31	0.29	-10000	0	-0.77	94	94
FCER2	-0.79	0.65	-10000	0	-1.4	308	308
PARP14	0.009	0.03	-10000	0	-10000	0	0
CCL17	-0.52	0.48	-10000	0	-1.2	127	127
GRB2	0.027	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.21	0.21	-10000	0	-0.73	26	26
T cell proliferation	-0.51	0.5	-10000	0	-1.3	133	133
IL4R/JAK1	-0.52	0.49	-10000	0	-1.2	134	134
EGR2	-0.59	0.52	-10000	0	-1.3	143	143
JAK2	-0.032	0.049	-10000	0	-0.39	3	3
JAK3	0.015	0.032	-10000	0	-0.44	1	1
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
JAK1	-0.006	0.025	-10000	0	-10000	0	0
COL1A2	-0.15	0.16	-10000	0	-0.55	16	16
CCL26	-0.53	0.48	-10000	0	-1.2	132	132
IL4R	-0.54	0.51	-10000	0	-1.3	130	130
PTPN6	0.038	0.014	-10000	0	-10000	0	0
IL13RA2	-0.53	0.48	-10000	0	-1.2	129	129
IL13RA1	-0.032	0.042	-10000	0	-10000	0	0
IRF4	-0.44	0.62	-10000	0	-1.4	171	171
ARG1	-0.089	0.14	-10000	0	-0.61	6	6
CBL	-0.35	0.33	-10000	0	-0.8	148	148
GTF3A	0.023	0.073	0.34	23	-0.44	1	24
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
IL13RA1/JAK2	-0.037	0.061	-10000	0	-0.28	3	3
IRF4/BCL6	-0.38	0.58	-10000	0	-1.3	171	171
CD40LG	-0.038	0.1	-10000	0	-0.38	42	42
MAPK14	-0.34	0.32	-10000	0	-0.82	134	134
mitosis	-0.26	0.27	-10000	0	-0.73	73	73
STAT6	-0.58	0.58	-10000	0	-1.4	155	155
SPI1	0.024	0.047	-10000	0	-0.36	9	9
RPS6KB1	-0.25	0.26	-10000	0	-0.72	67	67
STAT6 (dimer)	-0.58	0.57	-10000	0	-1.4	155	155
STAT6 (dimer)/PARP14	-0.59	0.55	-10000	0	-1.3	163	163
mast cell activation	0.014	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.29	0.29	-10000	0	-0.75	100	100
FRAP1	-0.27	0.29	-10000	0	-0.78	75	75
LTA	-0.52	0.49	-10000	0	-1.3	126	126
FES	0.025	0.023	-10000	0	-0.36	2	2
T-helper 1 cell differentiation	0.56	0.55	1.3	155	-10000	0	155
CCL11	-0.55	0.54	-10000	0	-1.3	157	157
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.26	0.27	-10000	0	-0.76	61	61
IL2RG	0.014	0.037	-10000	0	-0.35	3	3
IL10	-0.54	0.52	-10000	0	-1.3	141	141
IRS1	0.028	0.002	-10000	0	-10000	0	0
IRS2	0.022	0.012	-10000	0	-10000	0	0
IL4	-0.14	0.2	-10000	0	-1.1	17	17
IL5	-0.52	0.48	-10000	0	-1.2	146	146
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.41	0.38	-10000	0	-0.95	111	111
COL1A1	-0.19	0.21	-10000	0	-1	4	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.52	0.5	-10000	0	-1.3	125	125
IL2R gamma/JAK3	0.018	0.045	-10000	0	-0.27	4	4
TFF3	-0.53	0.5	-10000	0	-1.3	135	135
ALOX15	-0.53	0.5	-10000	0	-1.2	154	154
MYBL1	0.023	0.028	-10000	0	-0.44	2	2
T-helper 2 cell differentiation	-0.43	0.4	-10000	0	-0.99	137	137
SHC1	0.027	0.004	-10000	0	-10000	0	0
CEBPB	0.016	0.047	0.36	3	-0.44	4	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.24	0.27	-10000	0	-0.95	34	34
mol:PI-3-4-5-P3	-0.27	0.29	-10000	0	-0.78	75	75
PI3K	-0.28	0.31	-10000	0	-0.84	75	75
DOK2	0.016	0.045	-10000	0	-0.36	8	8
ETS1	0.036	0.026	-10000	0	-0.32	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.19	-10000	0	-0.65	29	29
ITGB3	-0.51	0.49	-10000	0	-1.2	142	142
PIGR	-0.69	0.65	-10000	0	-1.5	229	229
IGHE	0.082	0.073	0.18	126	-10000	0	126
MAPKKK cascade	-0.19	0.19	-10000	0	-0.64	29	29
BCL6	0.034	0.011	-10000	0	-10000	0	0
OPRM1	-0.52	0.48	-10000	0	-1.2	126	126
RETNLB	-0.74	0.66	-10000	0	-1.4	263	263
SELP	-0.57	0.56	-10000	0	-1.4	157	157
AICDA	-0.49	0.46	-10000	0	-1.2	136	136

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.11	0.2	0.34	2	-0.46	120	122
IKBKB	-0.037	0.11	0.28	3	-0.29	51	54
AKT1	-0.077	0.11	0.27	7	-0.26	112	119
IKBKG	-0.037	0.1	0.41	1	-0.28	54	55
CALM1	-0.097	0.21	0.29	1	-0.53	95	96
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
MAP3K1	-0.14	0.27	0.47	2	-0.62	115	117
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.1	0.23	0.31	1	-0.56	99	100
DOK1	0.028	0.001	-10000	0	-10000	0	0
AP-1	-0.067	0.11	0.24	2	-0.27	104	106
LYN	0.024	0.009	-10000	0	-10000	0	0
BLNK	0.022	0.041	-10000	0	-0.36	7	7
SHC1	0.027	0.004	-10000	0	-10000	0	0
BCR complex	-0.091	0.18	-10000	0	-0.32	220	220
CD22	-0.18	0.3	-10000	0	-0.62	154	154
CAMK2G	-0.092	0.19	0.28	1	-0.49	95	96
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
SHC/GRB2/SOS1	-0.047	0.12	-10000	0	-0.32	63	63
GO:0007205	-0.11	0.23	0.31	1	-0.57	99	100
SYK	0.027	0.004	-10000	0	-10000	0	0
ELK1	-0.1	0.22	0.29	1	-0.54	95	96
NFATC1	-0.16	0.24	0.31	2	-0.52	150	152
B-cell antigen/BCR complex	-0.091	0.18	-10000	0	-0.32	220	220
PAG1/CSK	0.03	0.039	-10000	0	-0.25	10	10
NFKBIB	-0.001	0.048	0.14	4	-0.13	32	36
HRAS	-0.082	0.18	0.25	3	-0.46	94	97
NFKBIA	0	0.047	0.14	4	-0.12	32	36
NF-kappa-B/RelA/I kappa B beta	0.005	0.04	0.16	3	-10000	0	3
RasGAP/Csk	-0.054	0.18	-10000	0	-0.41	91	91
mol:GDP	-0.098	0.22	0.3	1	-0.55	96	97
PTEN	0.026	0.006	-10000	0	-10000	0	0
CD79B	-0.024	0.13	-10000	0	-0.36	80	80
NF-kappa-B/RelA/I kappa B alpha	0.006	0.04	0.16	3	-10000	0	3
GRB2	0.027	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.17	0.26	0.33	2	-0.54	169	171
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	-0.11	0.24	0.31	1	-0.58	99	100
CSK	0.027	0.006	-10000	0	-10000	0	0
FOS	-0.096	0.2	0.28	1	-0.5	98	99
CHUK	-0.046	0.12	0.41	1	-0.29	71	72
IBTK	0.027	0.016	-10000	0	-0.36	1	1
CARD11/BCL10/MALT1/TAK1	-0.071	0.2	0.24	1	-0.47	91	92
PTPN6	-0.17	0.28	0.26	1	-0.59	150	151
RELA	0.027	0.004	-10000	0	-10000	0	0
BCL2A1	0.005	0.029	0.18	1	-0.13	1	2
VAV2	-0.18	0.3	-10000	0	-0.62	153	153
ubiquitin-dependent protein catabolic process	0.001	0.047	0.14	4	-0.12	31	35
BTK	-0.11	0.36	-10000	0	-1.1	74	74
CD19	-0.17	0.29	-10000	0	-0.59	163	163
MAP4K1	-0.006	0.11	-10000	0	-0.36	53	53
CD72	0.026	0.016	-10000	0	-0.36	1	1
PAG1	0.018	0.05	-10000	0	-0.36	10	10
MAPK14	-0.12	0.22	0.45	3	-0.52	113	116
SH3BP5	0.024	0.035	-10000	0	-0.36	5	5
PIK3AP1	-0.097	0.23	0.27	2	-0.56	98	100
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.13	0.28	-10000	0	-0.61	115	115
RAF1	-0.078	0.17	0.24	3	-0.43	93	96
RasGAP/p62DOK/SHIP	-0.05	0.18	-10000	0	-0.4	91	91
CD79A	-0.11	0.19	-10000	0	-0.36	219	219
re-entry into mitotic cell cycle	-0.067	0.11	0.24	2	-0.27	104	106
RASA1	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.067	0.14	0.23	4	-0.38	81	85
MAPK1	-0.067	0.14	0.22	3	-0.38	81	84
CD72/SHP1	-0.15	0.27	0.23	1	-0.56	147	148
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.12	0.22	0.45	2	-0.52	113	115
actin cytoskeleton organization	-0.14	0.24	0.31	2	-0.53	144	146
NF-kappa-B/RelA	0.014	0.079	0.33	2	-0.2	9	11
Calcineurin	-0.067	0.18	0.27	1	-0.47	82	83
PI3K	-0.15	0.22	-10000	0	-0.47	167	167
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.1	0.24	0.29	2	-0.58	103	105
SOS1	0.028	0.002	-10000	0	-10000	0	0
Bam32/HPK1	-0.17	0.35	-10000	0	-0.82	118	118
DAPP1	-0.19	0.38	-10000	0	-0.91	117	117
cytokine secretion	-0.14	0.22	0.3	2	-0.48	150	152
mol:DAG	-0.11	0.24	0.31	1	-0.58	99	100
PLCG2	-0.004	0.1	-10000	0	-0.36	49	49
MAP2K1	-0.074	0.16	0.24	3	-0.42	82	85
B-cell antigen/BCR complex/FcgammaRIIB	-0.084	0.2	-10000	0	-0.32	226	226
mol:PI-3-4-5-P3	-0.11	0.14	0.16	1	-0.35	121	122
ETS1	-0.085	0.18	0.26	1	-0.46	91	92
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.031	0.15	-10000	0	-0.35	65	65
B-cell antigen/BCR complex/LYN	-0.14	0.27	-10000	0	-0.64	114	114
MALT1	0.02	0.02	-10000	0	-0.36	1	1
TRAF6	0.028	0.003	-10000	0	-10000	0	0
RAC1	-0.15	0.27	0.31	2	-0.57	143	145
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.28	0.27	1	-0.58	140	141
CARD11	-0.097	0.23	0.26	5	-0.54	103	108
FCGR2B	-0.019	0.12	-10000	0	-0.36	72	72
PPP3CA	0.027	0.005	-10000	0	-10000	0	0
BCL10	0.026	0.016	-10000	0	-0.36	1	1
IKK complex	-0.011	0.048	0.14	9	-0.12	13	22
PTPRC	-0.003	0.1	-10000	0	-0.36	48	48
PDPK1	-0.078	0.1	0.18	7	-0.25	106	113
PPP3CB	0.027	0.004	-10000	0	-10000	0	0
PPP3CC	0.021	0.012	-10000	0	-10000	0	0
POU2F2	0.004	0.033	0.21	2	-10000	0	2

×

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

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
MAP4K1	-0.065	0.17	-10000	0	-0.42	101	101
CRKL	-0.055	0.16	0.2	1	-0.41	100	101
HRAS	-0.041	0.16	-10000	0	-0.37	104	104
mol:PIP3	-0.044	0.16	0.26	2	-0.38	96	98
SPRED1	0.026	0.007	-10000	0	-10000	0	0
SPRED2	0.028	0.001	-10000	0	-10000	0	0
GAB1	-0.056	0.17	-10000	0	-0.43	101	101
FOXO3	-0.051	0.18	0.29	2	-0.41	107	109
AKT1	-0.054	0.2	0.27	1	-0.44	108	109
BAD	-0.051	0.18	0.26	1	-0.41	108	109
megakaryocyte differentiation	-0.073	0.18	-10000	0	-0.44	103	103
GSK3B	-0.05	0.18	0.32	2	-0.41	106	108
RAF1	-0.036	0.13	0.24	1	-0.31	100	101
SHC1	0.027	0.004	-10000	0	-10000	0	0
STAT3	-0.057	0.17	-10000	0	-0.43	100	100
STAT1	-0.14	0.39	-10000	0	-0.95	111	111
HRAS/SPRED1	-0.024	0.14	-10000	0	-0.31	96	96
cell proliferation	-0.055	0.17	-10000	0	-0.42	101	101
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
TEC	0.026	0.02	-10000	0	-0.44	1	1
RPS6KB1	-0.051	0.18	-10000	0	-0.43	105	105
HRAS/SPRED2	-0.023	0.14	-10000	0	-0.31	99	99
LYN/TEC/p62DOK	-0.019	0.17	-10000	0	-0.41	85	85
MAPK3	-0.023	0.099	0.19	2	-0.26	39	41
STAP1	-0.092	0.19	-10000	0	-0.47	107	107
GRAP2	0.014	0.069	-10000	0	-0.36	20	20
JAK2	-0.12	0.34	-10000	0	-0.81	110	110
STAT1 (dimer)	-0.14	0.38	-10000	0	-0.93	111	111
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.032	0.2	-10000	0	-0.44	101	101
actin filament polymerization	-0.057	0.17	0.2	1	-0.41	100	101
LYN	0.024	0.009	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.11	0.25	-10000	0	-0.63	105	105
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.028	0.16	-10000	0	-0.38	98	98
PI3K	-0.027	0.19	-10000	0	-0.42	98	98
PTEN	0.026	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.15	0.46	-10000	0	-1.2	98	98
MAPK8	-0.057	0.17	-10000	0	-0.43	101	101
STAT3 (dimer)	-0.055	0.17	-10000	0	-0.42	100	100
positive regulation of transcription	-0.017	0.083	0.17	3	-0.21	37	40
mol:GDP	-0.039	0.17	-10000	0	-0.39	103	103
PIK3C2B	-0.056	0.17	-10000	0	-0.43	100	100
CBL/CRKL	-0.039	0.16	-10000	0	-0.39	100	100
FER	-0.058	0.17	-10000	0	-0.43	101	101
SH2B3	-0.056	0.17	-10000	0	-0.43	100	100
PDPK1	-0.04	0.15	0.25	5	-0.36	93	98
SNAI2	-0.055	0.16	-10000	0	-0.41	100	100
positive regulation of cell proliferation	-0.097	0.29	-10000	0	-0.7	110	110
KITLG	0.011	0.066	-10000	0	-0.39	14	14
cell motility	-0.097	0.29	-10000	0	-0.7	110	110
PTPN6	0.029	0.011	-10000	0	-10000	0	0
EPOR	-0.012	0.14	-10000	0	-1	2	2
STAT5A (dimer)	-0.076	0.24	-10000	0	-0.59	101	101
SOCS1	0.011	0.086	-10000	0	-0.44	21	21
cell migration	0.073	0.18	0.45	102	-10000	0	102
SOS1	0.028	0.002	-10000	0	-10000	0	0
EPO	0.012	0.051	0.35	2	-0.45	5	7
VAV1	0.011	0.077	-10000	0	-0.36	25	25
GRB10	-0.055	0.16	-10000	0	-0.41	97	97
PTPN11	0.029	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.056	0.18	-10000	0	-0.44	103	103
GO:0007205	0.003	0.009	-10000	0	-10000	0	0
MAP2K1	-0.029	0.11	0.22	1	-0.28	46	47
CBL	0.027	0.004	-10000	0	-10000	0	0
KIT	-0.17	0.47	-10000	0	-1.2	99	99
MAP2K2	-0.028	0.11	0.22	1	-0.28	44	45
SHC/Grb2/SOS1	-0.018	0.18	-10000	0	-0.41	97	97
STAT5A	-0.08	0.25	-10000	0	-0.61	101	101
GRB2	0.027	0.004	-10000	0	-10000	0	0
response to radiation	-0.054	0.16	-10000	0	-0.4	100	100
SHC/GRAP2	0.029	0.053	-10000	0	-0.25	20	20
PTPRO	-0.075	0.18	-10000	0	-0.45	103	103
SH2B2	-0.058	0.17	0.2	1	-0.42	100	101
DOK1	0.028	0.001	-10000	0	-10000	0	0
MATK	-0.074	0.18	-10000	0	-0.46	101	101
CREBBP	0.017	0.057	-10000	0	-10000	0	0
BCL2	-0.19	0.42	-10000	0	-1.2	67	67

×

Fc-epsilon receptor I signaling in mast cells

Figure S9. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S9. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.025	0.031	-10000	0	-0.36	4	4
LAT2	-0.085	0.15	-10000	0	-0.36	97	97
AP1	-0.11	0.23	-10000	0	-0.51	122	122
mol:PIP3	-0.11	0.19	0.32	7	-0.44	105	112
IKBKB	-0.067	0.13	0.21	26	-0.27	114	140
AKT1	-0.079	0.11	0.34	9	-0.38	7	16
IKBKG	-0.078	0.12	0.26	7	-0.27	123	130
MS4A2	-0.087	0.18	-10000	0	-0.36	177	177
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.026	0.016	-10000	0	-0.36	1	1
MAP3K1	-0.1	0.17	0.28	4	-0.4	110	114
mol:Ca2+	-0.085	0.15	0.28	8	-0.33	105	113
LYN	0.023	0.011	-10000	0	-10000	0	0
CBLB	-0.086	0.15	-10000	0	-0.33	118	118
SHC1	0.027	0.004	-10000	0	-10000	0	0
RasGAP/p62DOK	0.05	0.02	-10000	0	-0.19	3	3
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
PLD2	-0.083	0.13	0.31	12	-0.32	84	96
PTPN13	-0.096	0.18	-10000	0	-0.49	47	47
PTPN11	0.015	0.024	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.072	0.12	0.34	6	-0.29	62	68
SYK	0.026	0.009	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.2	0.18	1	-0.45	108	109
LAT	-0.087	0.15	-10000	0	-0.33	121	121
PAK2	-0.11	0.19	0.29	4	-0.44	115	119
NFATC2	-0.033	0.098	-10000	0	-0.52	19	19
HRAS	-0.12	0.2	0.26	5	-0.47	117	122
GAB2	0.027	0.004	-10000	0	-10000	0	0
PLA2G1B	0.019	0.12	-10000	0	-0.86	10	10
Fc epsilon R1	-0.084	0.17	-10000	0	-0.28	232	232
Antigen/IgE/Fc epsilon R1	-0.074	0.15	-10000	0	-0.28	177	177
mol:GDP	-0.13	0.23	-10000	0	-0.51	125	125
JUN	0.027	0.004	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.026	0.006	-10000	0	-10000	0	0
FOS	0.022	0.039	-10000	0	-0.36	6	6
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.088	0.16	-10000	0	-0.31	158	158
CHUK	-0.079	0.12	0.27	5	-0.27	123	128
KLRG1	-0.075	0.13	0.14	1	-0.33	91	92
VAV1	-0.094	0.16	-10000	0	-0.36	116	116
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.086	0.15	-10000	0	-0.35	99	99
negative regulation of mast cell degranulation	-0.064	0.13	-10000	0	-0.32	84	84
BTK	-0.14	0.26	-10000	0	-0.58	125	125
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.12	0.21	-10000	0	-0.49	120	120
GAB2/PI3K/SHP2	-0.093	0.1	-10000	0	-0.31	78	78
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.082	0.15	-10000	0	-0.38	91	91
RAF1	0.022	0.13	-10000	0	-0.93	10	10
Fc epsilon R1/FcgammaRIIB/SHIP	-0.073	0.19	-10000	0	-0.39	115	115
FCER1G	0.028	0.041	-10000	0	-0.37	6	6
FCER1A	-0.086	0.18	-10000	0	-0.37	168	168
Antigen/IgE/Fc epsilon R1/Fyn	-0.061	0.15	-10000	0	-0.3	122	122
MAPK3	0.02	0.12	-10000	0	-0.85	10	10
MAPK1	0.015	0.12	-10000	0	-0.89	10	10
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.1	0.26	-10000	0	-0.66	88	88
DUSP1	0.025	0.027	-10000	0	-0.36	3	3
NF-kappa-B/RelA	-0.04	0.08	0.11	1	-0.19	59	60
actin cytoskeleton reorganization	-0.089	0.18	-10000	0	-0.43	79	79
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.091	0.18	-10000	0	-0.42	103	103
FER	-0.084	0.15	-10000	0	-0.34	111	111
RELA	0.027	0.004	-10000	0	-10000	0	0
ITK	-0.035	0.095	-10000	0	-0.38	36	36
SOS1	0.028	0.002	-10000	0	-10000	0	0
PLCG1	-0.079	0.23	0.23	28	-0.49	105	133
cytokine secretion	-0.032	0.055	-10000	0	-0.16	5	5
SPHK1	-0.1	0.15	-10000	0	-0.32	155	155
PTK2	-0.093	0.18	-10000	0	-0.45	77	77
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.099	0.21	0.21	6	-0.47	109	115
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.11	0.19	0.31	7	-0.44	109	116
MAP2K2	0.015	0.12	-10000	0	-0.86	10	10
MAP2K1	0.013	0.12	-10000	0	-0.87	10	10
MAP2K7	0.027	0.016	-10000	0	-0.36	1	1
KLRG1/SHP2	-0.059	0.12	0.18	3	-0.3	84	87
MAP2K4	-0.14	0.37	-10000	0	-0.9	116	116
Fc epsilon R1/FcgammaRIIB	-0.086	0.19	-10000	0	-0.37	140	140
mol:Choline	-0.082	0.13	0.3	13	-0.31	84	97
SHC/Grb2/SOS1	-0.058	0.16	-10000	0	-0.36	85	85
FYN	0.027	0.005	-10000	0	-10000	0	0
DOK1	0.028	0.001	-10000	0	-10000	0	0
PXN	-0.088	0.17	0.41	2	-0.47	41	43
HCLS1	-0.088	0.15	-10000	0	-0.35	108	108
PRKCB	-0.11	0.17	0.31	5	-0.37	144	149
FCGR2B	-0.019	0.12	-10000	0	-0.36	72	72
IGHE	-0.003	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.065	0.14	-10000	0	-0.32	84	84
LCP2	0.023	0.039	-10000	0	-0.36	6	6
PLA2G4A	-0.1	0.17	-10000	0	-0.37	135	135
RASA1	0.027	0.005	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.082	0.13	0.3	13	-0.31	84	97
IKK complex	-0.049	0.1	0.2	21	-0.23	58	79
WIPF1	0.026	0.027	-10000	0	-0.36	3	3

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.28	0.28	-10000	0	-0.83	64	64
PCK1	-0.59	0.59	-10000	0	-1.2	268	268
HNF4A	-0.26	0.29	-10000	0	-0.91	43	43
KCNJ11	-0.29	0.29	-10000	0	-0.84	70	70
AKT1	-0.2	0.18	-10000	0	-0.58	45	45
response to starvation	-0.018	0.029	-10000	0	-10000	0	0
DLK1	-0.29	0.29	-10000	0	-0.86	68	68
NKX2-1	-0.12	0.14	0.34	5	-0.37	41	46
ACADM	-0.29	0.28	-10000	0	-0.81	81	81
TAT	-0.59	0.57	-10000	0	-1.2	246	246
CEBPB	0.004	0.052	0.36	3	-0.44	4	7
CEBPA	0.006	0.047	-10000	0	-0.36	3	3
TTR	-0.34	0.47	0.52	2	-1.1	140	142
PKLR	-0.34	0.34	-10000	0	-0.91	119	119
APOA1	-0.3	0.32	-10000	0	-0.96	53	53
CPT1C	-0.29	0.27	-10000	0	-0.81	74	74
ALAS1	-0.14	0.14	-10000	0	-0.6	2	2
TFRC	-0.27	0.23	-10000	0	-0.66	64	64
FOXF1	0.021	0.049	-10000	0	-0.36	10	10
NF1	0.031	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	-0.073	0.051	-10000	0	-0.28	6	6
CPT1A	-0.29	0.27	-10000	0	-0.82	69	69
HMGCS1	-0.29	0.28	-10000	0	-0.79	81	81
NR3C1	-0.076	0.13	-10000	0	-0.31	89	89
CPT1B	-0.29	0.28	-10000	0	-0.82	72	72
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.066	0.039	-10000	0	-10000	0	0
GCK	-0.29	0.29	-10000	0	-0.87	67	67
CREB1	-0.063	0.11	-10000	0	-0.23	86	86
IGFBP1	-0.22	0.2	-10000	0	-0.59	77	77
PDX1	-0.31	0.18	-10000	0	-0.63	26	26
UCP2	-0.29	0.27	-10000	0	-0.8	75	75
ALDOB	-0.32	0.32	-10000	0	-0.92	80	80
AFP	-0.11	0.13	-10000	0	-0.43	46	46
BDH1	-0.29	0.28	-10000	0	-0.81	75	75
HADH	-0.28	0.28	-10000	0	-0.84	64	64
F2	-0.32	0.32	-10000	0	-1	51	51
HNF1A	-0.073	0.051	-10000	0	-0.28	6	6
G6PC	-0.16	0.32	-10000	0	-1.2	45	45
SLC2A2	-0.22	0.18	-10000	0	-0.78	8	8
INS	-0.006	0.04	-10000	0	-10000	0	0
FOXA1	-0.035	0.12	-10000	0	-0.36	56	56
FOXA3	-0.15	0.14	-10000	0	-0.34	121	121
FOXA2	-0.33	0.32	-10000	0	-0.88	91	91
ABCC8	-0.34	0.34	-10000	0	-0.97	95	95
ALB	-0.11	0.14	-10000	0	-0.46	39	39

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.016	0.073	-10000	0	-0.4	14	14
Crk/p130 Cas/Paxillin	-0.089	0.12	-10000	0	-0.31	57	57
JUN	-0.084	0.12	-10000	0	-0.34	64	64
HRAS	0.027	0.016	-10000	0	-0.36	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.06	0.15	-10000	0	-0.37	52	52
RAP1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.027	0.003	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.063	0.16	-10000	0	-0.37	59	59
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.01	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.042	0.12	-10000	0	-0.19	225	225
RHOA	0.027	0.004	-10000	0	-10000	0	0
RAP1A/GTP	-0.055	0.14	-10000	0	-0.33	57	57
GRB7	0.035	0.049	0.36	14	-10000	0	14
RET51/GFRalpha1/GDNF	-0.063	0.16	-10000	0	-0.36	63	63
MAPKKK cascade	-0.078	0.14	-10000	0	-0.37	55	55
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.042	0.12	-10000	0	-0.19	228	228
lamellipodium assembly	-0.077	0.12	-10000	0	-0.28	64	64
RET51/GFRalpha1/GDNF/SHC	-0.062	0.16	-10000	0	-0.36	63	63
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
RET9/GFRalpha1/GDNF/SHC	-0.04	0.12	-10000	0	-0.19	223	223
RET9/GFRalpha1/GDNF/Shank3	-0.042	0.12	-10000	0	-0.19	216	216
MAPK3	-0.091	0.11	-10000	0	-0.32	57	57
DOK1	0.028	0.001	-10000	0	-10000	0	0
DOK6	0.014	0.048	-10000	0	-0.36	9	9
PXN	0.028	0.002	-10000	0	-10000	0	0
neurite development	-0.067	0.099	-10000	0	-0.32	37	37
DOK5	0.012	0.047	0.36	1	-0.36	8	9
GFRA1	-0.12	0.19	-10000	0	-0.36	235	235
MAPK8	-0.087	0.13	-10000	0	-0.35	71	71
HRAS/GTP	-0.076	0.17	-10000	0	-0.41	59	59
tube development	-0.039	0.11	0.21	1	-0.35	1	2
MAPK1	-0.089	0.11	0.34	1	-0.32	56	57
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.056	0.1	-10000	0	-0.19	223	223
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
PDLIM7	0.027	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.045	0.12	-10000	0	-0.35	41	41
SHC1	0.027	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.063	0.16	-10000	0	-0.37	57	57
RET51/GFRalpha1/GDNF/Dok5	-0.049	0.13	0.26	1	-0.37	38	39
PRKCA	0.027	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.011	-10000	0	-0.25	1	1
CREB1	-0.086	0.14	-10000	0	-0.26	225	225
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.057	0.11	-10000	0	-0.2	220	220
RET51/GFRalpha1/GDNF/Grb7	-0.058	0.15	0.25	5	-0.35	59	64
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.032	0.14	-10000	0	-0.36	93	93
DOK4	0.027	0.016	-10000	0	-0.36	1	1
JNK cascade	-0.082	0.12	-10000	0	-0.34	64	64
RET9/GFRalpha1/GDNF/FRS2	-0.041	0.12	-10000	0	-0.19	226	226
SHANK3	0.026	0.017	-10000	0	-0.36	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.028	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.055	0.1	-10000	0	-0.19	220	220
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.083	0.14	-10000	0	-0.36	67	67
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.086	0.14	-10000	0	-0.37	71	71
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.09	0.16	-10000	0	-0.44	65	65
PI3K	-0.11	0.17	-10000	0	-0.34	186	186
SOS1	0.028	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.031	0.12	-10000	0	-0.35	1	1
GRB10	0.025	0.008	-10000	0	-10000	0	0
activation of MAPKK activity	-0.071	0.12	-10000	0	-0.31	59	59
RET51/GFRalpha1/GDNF/FRS2	-0.063	0.16	-10000	0	-0.37	58	58
GAB1	0.027	0.005	-10000	0	-10000	0	0
IRS1	0.028	0.002	-10000	0	-10000	0	0
IRS2	0.022	0.012	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.09	0.16	-10000	0	-0.43	68	68
RET51/GFRalpha1/GDNF/PKC alpha	-0.062	0.15	-10000	0	-0.37	54	54
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GDNF	0.016	0.025	-10000	0	-0.36	1	1
RAC1	0.025	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.063	0.16	-10000	0	-0.37	59	59
Rac1/GTP	-0.088	0.14	-10000	0	-0.34	64	64
RET9/GFRalpha1/GDNF	-0.058	0.12	-10000	0	-0.21	230	230
GFRalpha1/GDNF	-0.072	0.14	-10000	0	-0.25	230	230

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.027	0.019	-10000	0	-0.44	1	1
CCL5	0.012	0.075	-10000	0	-0.36	24	24
SDCBP	0.024	0.018	-10000	0	-0.36	1	1
FGFR/FGF2/Syndecan-1	-0.12	0.1	0.29	3	-0.32	45	48
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.092	0.1	0.23	3	-0.3	41	44
Syndecan-1/Syntenin	-0.11	0.1	0.28	2	-0.31	41	43
MAPK3	-0.11	0.094	0.26	2	-0.36	18	20
HGF/MET	0.029	0.058	-10000	0	-0.28	19	19
TGFB1/TGF beta receptor Type II	0.026	0.019	-10000	0	-0.44	1	1
BSG	0.027	0.016	-10000	0	-0.36	1	1
keratinocyte migration	-0.091	0.1	0.23	3	-0.3	41	44
Syndecan-1/RANTES	-0.12	0.11	0.26	3	-0.32	53	56
Syndecan-1/CD147	-0.11	0.1	0.35	1	-0.36	22	23
Syndecan-1/Syntenin/PIP2	-0.1	0.097	0.26	2	-0.3	41	43
LAMA5	0.017	0.036	0.36	3	-0.4	2	5
positive regulation of cell-cell adhesion	-0.1	0.095	0.26	2	-0.3	41	43
MMP7	-0.42	0.11	0.36	3	-0.45	583	586
HGF	0.017	0.061	-10000	0	-0.37	15	15
Syndecan-1/CASK	-0.12	0.096	0.28	2	-0.31	46	48
Syndecan-1/HGF/MET	-0.11	0.11	0.35	1	-0.36	30	31
regulation of cell adhesion	-0.11	0.091	0.25	2	-0.36	16	18
HPSE	0.023	0.038	-10000	0	-0.36	6	6
positive regulation of cell migration	-0.12	0.1	0.29	3	-0.32	45	48
SDC1	-0.12	0.1	0.29	3	-0.32	45	48
Syndecan-1/Collagen	-0.12	0.1	0.29	3	-0.32	45	48
PPIB	0.026	0.006	-10000	0	-10000	0	0
MET	0.023	0.045	0.36	1	-0.44	5	6
PRKACA	0.027	0.003	-10000	0	-10000	0	0
MMP9	0	0.12	0.36	15	-0.44	32	47
MAPK1	-0.11	0.093	0.26	2	-0.35	19	21
homophilic cell adhesion	-0.12	0.1	0.29	3	-0.32	46	49
MMP1	-0.28	0.23	0.36	2	-0.44	397	399

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.04	0.008	-10000	0	-10000	0	0
Necdin/E2F1	0.018	0.058	0.26	7	-0.27	17	24
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0	0.12	-10000	0	-0.34	10	10
NGF (dimer)/p75(NTR)/BEX1	-0.083	0.16	-10000	0	-0.26	255	255
NT-4/5 (dimer)/p75(NTR)	-0.047	0.14	-10000	0	-0.27	164	164
IKBKB	0.024	0.009	-10000	0	-10000	0	0
AKT1	-0.037	0.09	-10000	0	-0.34	8	8
IKBKG	0.027	0.016	-10000	0	-0.36	1	1
BDNF	0.019	0.06	-10000	0	-0.44	10	10
MGDIs/NGR/p75(NTR)/LINGO1	-0.035	0.14	-10000	0	-0.24	173	173
FURIN	0.026	0.017	-10000	0	-0.36	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.016	0.12	-10000	0	-0.22	152	152
LINGO1	0.008	0.091	-10000	0	-0.44	24	24
Sortilin/TRAF6/NRIF	0.031	0.027	-10000	0	-0.32	1	1
proBDNF (dimer)	0.019	0.06	-10000	0	-0.44	10	10
NTRK1	0.016	0.057	-10000	0	-0.43	9	9
RTN4R	0.011	0.084	-10000	0	-0.44	21	21
neuron apoptosis	-0.049	0.14	0.32	2	-0.43	27	29
IRAK1	0.027	0.019	-10000	0	-0.44	1	1
SHC1	-0.045	0.1	-10000	0	-0.22	147	147
ARHGDIA	0.027	0.016	-10000	0	-0.36	1	1
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.071	0.031	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.005	0.12	-10000	0	-0.36	11	11
MAGEH1	0.024	0.038	-10000	0	-0.36	6	6
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.013	0.13	-10000	0	-0.36	25	25
Mammalian IAPs/DIABLO	0.064	0.038	-10000	0	-0.25	1	1
proNGF (dimer)	0.011	0.071	-10000	0	-0.37	20	20
MAGED1	0.027	0.003	-10000	0	-10000	0	0
APP	0.026	0.017	-10000	0	-0.36	1	1
NT-4/5 (dimer)	-0.017	0.088	-10000	0	-0.45	23	23
ZNF274	0.023	0.038	-10000	0	-0.36	6	6
RhoA/GDP/RHOGDI	-0.021	0.1	-10000	0	-0.32	10	10
NGF	0.011	0.071	-10000	0	-0.37	20	20
cell cycle arrest	-0.031	0.09	0.2	6	-0.31	9	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.027	0.097	-10000	0	-0.31	16	16
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.13	-10000	0	-0.23	164	164
NCSTN	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	-0.047	0.14	-10000	0	-0.24	198	198
PSENEN	0.026	0.016	-10000	0	-0.36	1	1
mol:ceramide	-0.038	0.096	0.18	6	-0.34	10	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.024	0.089	-10000	0	-0.3	22	22
p75(NTR)/beta APP	-0.032	0.12	-10000	0	-0.25	150	150
BEX1	-0.084	0.17	-10000	0	-0.36	164	164
mol:GDP	-0.062	0.095	-10000	0	-0.22	154	154
NGF (dimer)	-0.28	0.12	-10000	0	-0.3	578	578
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.019	0.13	-10000	0	-0.29	41	41
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
RAC1/GTP	-0.015	0.1	-10000	0	-0.19	143	143
MYD88	0.027	0.003	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.047	0.14	-10000	0	-0.24	198	198
RHOB	0.028	0	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.024	0.043	0.26	8	-0.32	4	12
NT3 (dimer)	0.021	0.043	-10000	0	-0.37	7	7
TP53	-0.044	0.079	0.35	3	-0.34	4	7
PRDM4	-0.041	0.098	-10000	0	-0.34	10	10
BDNF (dimer)	-0.46	0.15	0.4	1	-0.48	600	601
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
SORT1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.004	0.11	-10000	0	-0.34	10	10
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.004	0.12	-10000	0	-0.34	10	10
RHOC	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.028	0.002	-10000	0	-10000	0	0
MAPK10	-0.068	0.15	0.31	5	-0.41	49	54
DIABLO	0.028	0.003	-10000	0	-10000	0	0
SMPD2	-0.039	0.097	-10000	0	-0.34	10	10
APH1B	0.026	0.006	-10000	0	-10000	0	0
APH1A	0.027	0.004	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.019	0.12	-10000	0	-0.22	152	152
PSEN1	0.026	0.007	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.039	0.01	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.033	0.13	-10000	0	-0.26	149	149
MAPK8	-0.048	0.12	0.33	4	-0.33	22	26
MAPK9	-0.047	0.12	0.33	4	-0.34	18	22
APAF1	0.028	0.003	-10000	0	-10000	0	0
NTF3	0.021	0.043	-10000	0	-0.37	7	7
NTF4	-0.017	0.089	-10000	0	-0.45	23	23
NDN	0.011	0.075	-10000	0	-0.36	24	24
RAC1/GDP	0.019	0.006	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.02	0.13	-10000	0	-0.34	30	30
p75 CTF/Sortilin/TRAF6/NRIF	0.065	0.031	-10000	0	-0.19	6	6
RhoA-B-C/GTP	-0.047	0.14	-10000	0	-0.24	198	198
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.008	0.12	-10000	0	-0.27	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.001	0.12	-10000	0	-0.26	10	10
PRKACB	-0.019	0.12	-10000	0	-0.36	72	72
proBDNF (dimer)/p75 ECD	0.035	0.046	-10000	0	-0.32	10	10
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.021	0.05	-10000	0	-0.37	10	10
BIRC2	0.026	0.016	-10000	0	-0.36	1	1
neuron projection morphogenesis	-0.053	0.12	-10000	0	-0.31	44	44
BAD	-0.062	0.14	0.28	6	-0.35	47	53
RIPK2	0.024	0.01	-10000	0	-10000	0	0
NGFR	-0.067	0.17	-10000	0	-0.36	149	149
CYCS	-0.038	0.089	-10000	0	-0.34	8	8
ADAM17	0.028	0.002	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.004	0.11	-10000	0	-0.34	8	8
BCL2L11	-0.062	0.14	0.3	5	-0.35	46	51
BDNF (dimer)/p75(NTR)	-0.037	0.13	-10000	0	-0.26	158	158
PI3K	-0.005	0.12	-10000	0	-0.34	10	10
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.005	0.12	-10000	0	-0.34	10	10
NDNL2	0.026	0.007	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
PRKCI	0.026	0.022	-10000	0	-0.36	2	2
NGF (dimer)/p75(NTR)	-0.04	0.14	-10000	0	-0.26	160	160
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.002	0.12	-10000	0	-0.34	10	10
TRAF6	0.027	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
PLG	-0.095	0.18	0.36	1	-0.45	127	128
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.046	0.11	-10000	0	-0.39	9	9
SQSTM1	0.027	0.004	-10000	0	-10000	0	0
NGFRAP1	0.026	0.022	-10000	0	-0.36	2	2
CASP3	-0.061	0.13	0.31	4	-0.33	49	53
E2F1	0.019	0.057	0.36	9	-0.44	4	13
CASP9	0.026	0.007	-10000	0	-10000	0	0
IKK complex	0	0.11	-10000	0	-0.36	11	11
NGF (dimer)/TRKA	0.023	0.069	-10000	0	-0.28	28	28
MMP7	-0.42	0.11	0.36	3	-0.45	583	586
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.005	0.12	-10000	0	-0.35	11	11
MMP3	-0.36	0.18	0.36	1	-0.45	509	510
APAF-1/Caspase 9	-0.054	0.068	-10000	0	-0.3	11	11

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.014	0.099	-10000	0	-0.41	27	27
IHH	0.021	0.077	-10000	0	-0.42	16	16
SHH Np/Cholesterol/GAS1	-0.055	0.13	0.18	4	-0.24	183	187
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.054	0.13	0.24	183	-0.18	4	187
SMO/beta Arrestin2	0.018	0.088	-10000	0	-0.44	9	9
SMO	0.004	0.083	-10000	0	-0.46	9	9
AKT1	0	0.11	-10000	0	-0.4	19	19
ARRB2	0.023	0.01	-10000	0	-10000	0	0
BOC	0.011	0.078	-10000	0	-0.36	26	26
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
heart looping	0.006	0.083	-10000	0	-0.45	9	9
STIL	-0.022	0.11	0.34	1	-0.35	13	14
DHH N/PTCH2	0.027	0.061	-10000	0	-0.26	26	26
DHH N/PTCH1	0.024	0.085	-10000	0	-0.37	13	13
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
DHH	0.011	0.072	-10000	0	-0.36	22	22
PTHLH	0.007	0.13	-10000	0	-0.73	14	14
determination of left/right symmetry	0.006	0.083	-10000	0	-0.45	9	9
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
skeletal system development	0.007	0.13	-10000	0	-0.72	14	14
IHH N/Hhip	-0.022	0.13	-10000	0	-0.29	117	117
DHH N/Hhip	-0.022	0.13	-10000	0	-0.27	120	120
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.006	0.083	-10000	0	-0.45	9	9
pancreas development	-0.043	0.15	-10000	0	-0.36	109	109
HHAT	0.024	0.035	-10000	0	-0.36	5	5
PI3K	0.039	0.015	-10000	0	-0.25	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.035	0.14	-10000	0	-0.36	97	97
somite specification	0.006	0.083	-10000	0	-0.45	9	9
SHH Np/Cholesterol/PTCH1	-0.023	0.11	0.19	5	-0.33	18	23
SHH Np/Cholesterol/PTCH2	-0.026	0.11	0.18	5	-0.24	123	128
SHH Np/Cholesterol/Megalin	-0.048	0.13	0.18	5	-0.26	158	163
SHH	-0.047	0.13	0.32	6	-0.32	118	124
catabolic process	0.019	0.077	-10000	0	-0.38	13	13
SMO/Vitamin D3	-0.019	0.11	-10000	0	-0.4	13	13
SHH Np/Cholesterol/Hhip	-0.059	0.13	0.18	5	-0.23	204	209
LRP2	-0.036	0.13	-10000	0	-0.44	56	56
receptor-mediated endocytosis	-0.033	0.12	0.23	3	-0.37	26	29
SHH Np/Cholesterol/BOC	-0.032	0.11	0.18	4	-0.24	138	142
SHH Np/Cholesterol/CDO	-0.025	0.11	0.18	4	-0.24	119	123
mesenchymal cell differentiation	0.059	0.13	0.23	204	-0.18	5	209
mol:Vitamin D3	-0.017	0.12	0.22	11	-0.36	14	25
IHH N/PTCH2	0.031	0.059	-10000	0	-0.27	20	20
CDON	0.027	0.004	-10000	0	-10000	0	0
IHH N/PTCH1	0.027	0.08	-10000	0	-0.38	13	13
Megalin/LRPAP1	0.004	0.1	-10000	0	-0.32	56	56
PTCH2	0.024	0.038	-10000	0	-0.44	4	4
SHH Np/Cholesterol	-0.034	0.1	-10000	0	-0.24	119	119
PTCH1	0.019	0.077	-10000	0	-0.38	13	13
HHIP	-0.043	0.15	-10000	0	-0.36	109	109

×

HIF-1-alpha transcription factor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.41	0.27	-10000	0	-0.86	89	89
HDAC7	0.027	0.007	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.33	0.24	-10000	0	-0.88	34	34
SMAD4	0.02	0.013	-10000	0	-10000	0	0
ID2	-0.41	0.28	-10000	0	-0.89	71	71
AP1	0.036	0.031	-10000	0	-0.25	6	6
ABCG2	-0.55	0.3	-10000	0	-0.92	150	150
HIF1A	-0.079	0.051	-10000	0	-10000	0	0
TFF3	-0.41	0.28	-10000	0	-0.9	76	76
GATA2	0.022	0.052	-10000	0	-0.36	11	11
AKT1	-0.078	0.055	-10000	0	-10000	0	0
response to hypoxia	-0.081	0.046	-10000	0	-0.21	15	15
MCL1	-0.41	0.28	-10000	0	-0.89	71	71
NDRG1	-0.39	0.28	-10000	0	-0.89	66	66
SERPINE1	-0.45	0.3	-10000	0	-0.9	111	111
FECH	-0.4	0.28	-10000	0	-0.89	67	67
FURIN	-0.41	0.28	-10000	0	-0.89	69	69
NCOA2	0.023	0.029	-10000	0	-0.36	3	3
EP300	-0.074	0.075	-10000	0	-0.32	24	24
HMOX1	-0.41	0.28	-10000	0	-0.9	71	71
BHLHE40	-0.41	0.28	-10000	0	-0.89	74	74
BHLHE41	-0.41	0.28	-10000	0	-0.9	80	80
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.074	0.083	-10000	0	-10000	0	0
ENG	-0.077	0.068	0.28	2	-10000	0	2
JUN	0.028	0.005	-10000	0	-10000	0	0
RORA	-0.41	0.28	-10000	0	-0.88	78	78
ABCB1	-0.27	0.4	-10000	0	-1.1	118	118
TFRC	-0.41	0.28	-10000	0	-0.89	69	69
CXCR4	-0.41	0.28	-10000	0	-0.89	73	73
TF	-0.43	0.29	-10000	0	-0.91	91	91
CITED2	-0.41	0.28	-10000	0	-0.89	71	71
HIF1A/ARNT	-0.44	0.32	-10000	0	-0.99	70	70
LDHA	-0.039	0.055	-10000	0	-0.8	1	1
ETS1	-0.41	0.28	-10000	0	-0.89	71	71
PGK1	-0.41	0.28	-10000	0	-0.88	74	74
NOS2	-0.42	0.28	-10000	0	-0.9	83	83
ITGB2	-0.41	0.28	-10000	0	-0.9	71	71
ALDOA	-0.41	0.28	-10000	0	-0.89	71	71
Cbp/p300/CITED2	-0.4	0.29	-10000	0	-0.97	58	58
FOS	0.023	0.039	-10000	0	-0.36	6	6
HK2	-0.41	0.28	-10000	0	-0.89	71	71
SP1	0.008	0.053	-10000	0	-10000	0	0
GCK	-0.098	0.2	-10000	0	-1.3	12	12
HK1	-0.41	0.28	-10000	0	-0.88	76	76
NPM1	-0.41	0.28	-10000	0	-0.89	71	71
EGLN1	-0.41	0.28	-10000	0	-0.89	71	71
CREB1	0.033	0	-10000	0	-10000	0	0
PGM1	-0.41	0.28	-10000	0	-0.89	74	74
SMAD3	0.027	0.007	-10000	0	-10000	0	0
EDN1	-0.075	0.11	-10000	0	-0.77	4	4
IGFBP1	-0.43	0.3	-10000	0	-0.92	96	96
VEGFA	-0.3	0.21	-10000	0	-0.79	29	29
HIF1A/JAB1	-0.04	0.044	-10000	0	-10000	0	0
CP	-0.49	0.31	-10000	0	-0.91	126	126
CXCL12	-0.44	0.3	-10000	0	-0.91	99	99
COPS5	0.024	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4	0.03	0.019	-10000	0	-10000	0	0
BNIP3	-0.41	0.28	-10000	0	-0.89	72	72
EGLN3	-0.41	0.28	-10000	0	-0.9	66	66
CA9	-0.56	0.3	-10000	0	-0.92	165	165
TERT	-0.42	0.29	-10000	0	-0.92	83	83
ENO1	-0.41	0.28	-10000	0	-0.88	78	78
PFKL	-0.41	0.28	-10000	0	-0.89	71	71
NCOA1	0.028	0.002	-10000	0	-10000	0	0
ADM	-0.41	0.28	-10000	0	-0.89	70	70
ARNT	-0.082	0.05	-10000	0	-0.42	1	1
HNF4A	0.014	0.025	-10000	0	-0.36	1	1
ADFP	-0.41	0.27	-10000	0	-0.86	89	89
SLC2A1	-0.31	0.22	-10000	0	-0.82	37	37
LEP	-0.42	0.29	-10000	0	-0.89	95	95
HIF1A/ARNT/Cbp/p300	-0.34	0.24	-10000	0	-0.89	37	37
EPO	-0.23	0.18	-10000	0	-0.79	13	13
CREBBP	-0.073	0.072	-10000	0	-0.34	16	16
HIF1A/ARNT/Cbp/p300/HDAC7	-0.33	0.25	-10000	0	-0.93	31	31
PFKFB3	-0.41	0.28	-10000	0	-0.89	71	71
NT5E	-0.41	0.28	-10000	0	-0.89	75	75

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.009	0.17	0.25	84	-0.26	136	220
SMAD6-7/SMURF1	0.039	0.032	-10000	0	-0.23	3	3
NOG	0.014	0.033	-10000	0	-0.44	2	2
SMAD9	-0.048	0.18	-10000	0	-0.54	64	64
SMAD4	0.02	0.013	-10000	0	-10000	0	0
SMAD5	-0.033	0.12	-10000	0	-0.4	37	37
BMP7/USAG1	-0.05	0.2	0.26	75	-0.33	171	246
SMAD5/SKI	-0.035	0.13	0.21	2	-0.39	43	45
SMAD1	0.011	0.05	-10000	0	-0.39	4	4
BMP2	0.008	0.075	-10000	0	-0.36	24	24
SMAD1/SMAD1/SMAD4	0.02	0.06	-10000	0	-0.35	7	7
BMPR1A	0.026	0.006	-10000	0	-10000	0	0
BMPR1B	-0.013	0.12	-10000	0	-0.42	47	47
BMPR1A-1B/BAMBI	0.011	0.11	0.25	1	-0.26	78	79
AHSG	-0.041	0.15	0.36	2	-0.44	73	75
CER1	-0.012	0.072	0.36	2	-0.44	14	16
BMP2-4/CER1	0.003	0.1	0.25	1	-0.26	70	71
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.04	0.13	-10000	0	-0.35	47	47
BMP2-4 (homodimer)	-0.001	0.1	-10000	0	-0.3	61	61
RGMB	0.027	0.006	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.032	0.093	-10000	0	-0.25	36	36
RGMA	-0.052	0.16	-10000	0	-0.36	124	124
SMURF1	0.026	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.041	0.12	-10000	0	-0.34	49	49
BMP2-4/USAG1	-0.027	0.13	-10000	0	-0.25	131	131
SMAD6/SMURF1/SMAD5	-0.037	0.13	-10000	0	-0.42	34	34
SOSTDC1	-0.041	0.14	-10000	0	-0.36	103	103
BMP7/BMPR2/BMPR1A-1B	-0.007	0.17	0.25	89	-0.26	146	235
SKI	0.026	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.013	0.074	-10000	0	-0.36	23	23
HFE2	-0.008	0.031	-10000	0	-0.44	2	2
ZFYVE16	0.026	0.023	-10000	0	-0.36	2	2
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	0.013	0.094	-10000	0	-0.26	60	60
SMAD5/SMAD5/SMAD4	-0.033	0.13	0.21	2	-0.38	43	45
MAPK1	0.026	0.006	-10000	0	-10000	0	0
TAK1/TAB family	-0.028	0.11	-10000	0	-0.32	38	38
BMP7 (homodimer)	-0.026	0.25	0.36	101	-0.44	133	234
NUP214	0.027	0.004	-10000	0	-10000	0	0
BMP6/FETUA	-0.014	0.13	0.26	1	-0.31	91	92
SMAD1/SKI	0.016	0.07	-10000	0	-0.41	8	8
SMAD6	0.025	0.027	-10000	0	-0.44	2	2
CTDSP2	0.028	0.002	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.02	0.13	0.25	1	-0.28	114	115
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.006	0.09	-10000	0	-0.39	30	30
BMPR2 (homodimer)	0.027	0.016	-10000	0	-0.36	1	1
GADD34/PP1CA	0.052	0.02	-10000	0	-0.21	2	2
BMPR1A-1B (homodimer)	0.012	0.09	-10000	0	-0.3	47	47
CHRDL1	-0.18	0.19	-10000	0	-0.36	330	330
ENDOFIN/SMAD1	0.016	0.072	-10000	0	-0.43	7	7
SMAD6-7/SMURF1/SMAD1	0.031	0.072	-10000	0	-0.39	7	7
SMAD6/SMURF1	0.026	0.006	-10000	0	-10000	0	0
BAMBI	0.001	0.11	0.36	1	-0.44	35	36
SMURF2	0.025	0.025	-10000	0	-0.4	2	2
BMP2-4/CHRDL1	-0.1	0.15	-10000	0	-0.24	289	289
BMP2-4/GREM1	-0.001	0.11	-10000	0	-0.26	83	83
SMAD7	0.02	0.02	-10000	0	-0.36	1	1
SMAD8A/SMAD8A/SMAD4	-0.045	0.18	-10000	0	-0.49	78	78
SMAD1/SMAD6	0.014	0.072	-10000	0	-0.42	8	8
TAK1/SMAD6	0.038	0.01	-10000	0	-10000	0	0
BMP7	-0.026	0.25	0.36	101	-0.44	133	234
BMP6	0.013	0.074	-10000	0	-0.36	23	23
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.048	0.13	-10000	0	-0.36	65	65
PPM1A	0.026	0.007	-10000	0	-10000	0	0
SMAD1/SMURF2	0.015	0.073	-10000	0	-0.41	9	9
SMAD7/SMURF1	0.029	0.022	-10000	0	-0.25	1	1
CTDSPL	0.027	0.003	-10000	0	-10000	0	0
PPP1CA	0.027	0.004	-10000	0	-10000	0	0
XIAP	0.028	0.002	-10000	0	-10000	0	0
CTDSP1	0.028	0.001	-10000	0	-10000	0	0
PPP1R15A	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.053	0.14	-10000	0	-0.38	72	72
CHRD	0.027	0.016	-10000	0	-0.36	1	1
BMPR2	0.027	0.016	-10000	0	-0.36	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.047	0.12	-10000	0	-0.35	59	59
BMP4	-0.005	0.12	-10000	0	-0.44	41	41
FST	0.012	0.075	-10000	0	-0.37	23	23
BMP2-4/NOG	0.011	0.095	-10000	0	-0.26	61	61
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.005	0.16	0.25	77	-0.25	132	209

×

Visual signal transduction: Rods

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
mol:K +	0.026	0.006	-10000	0	-10000	0	0
GNAT1/GTP	0.014	0.014	-10000	0	-0.31	1	1
Metarhodopsin II/Arrestin	0.024	0.021	-10000	0	-0.27	3	3
PDE6G/GNAT1/GTP	0.017	0.057	-10000	0	-0.21	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.009	0.025	-10000	0	-0.44	1	1
GRK1	-0.01	0.032	0.36	1	-0.44	2	3
CNG Channel	-0.13	0.15	-10000	0	-0.36	112	112
mol:Na +	-0.034	0.13	-10000	0	-0.39	32	32
mol:ADP	-0.01	0.032	0.36	1	-0.44	2	3
RGS9-1/Gbeta5/R9AP	0.009	0.096	0.25	1	-0.21	94	95
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.028	0.13	-10000	0	-0.4	32	32
CNGB1	-0.047	0.13	-10000	0	-0.36	83	83
RDH5	0	0.1	-10000	0	-0.36	44	44
SAG	-0.009	0.018	-10000	0	-10000	0	0
mol:Ca2+	-0.067	0.12	0.34	13	-0.38	31	44
Na + (4 Units)	-0.035	0.12	-10000	0	-0.37	32	32
RGS9	-0.033	0.14	-10000	0	-0.36	93	93
GNB1/GNGT1	-0.055	0.16	0.26	14	-0.32	167	181
GNAT1/GDP	0.016	0.088	0.24	1	-0.2	18	19
GUCY2D	-0.006	0.094	-10000	0	-0.46	24	24
GNGT1	-0.1	0.22	0.36	15	-0.44	167	182
GUCY2F	-0.016	0.02	-10000	0	-0.44	1	1
GNB5	0.026	0.006	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.11	0.12	-10000	0	-0.35	40	40
mol:11-cis-retinal	0	0.1	-10000	0	-0.36	44	44
mol:cGMP	0.01	0.093	-10000	0	-0.27	55	55
GNB1	0.026	0.006	-10000	0	-10000	0	0
Rhodopsin	0.011	0.078	-10000	0	-0.26	47	47
SLC24A1	0.027	0.006	-10000	0	-10000	0	0
CNGA1	-0.007	0.11	-10000	0	-0.36	54	54
Metarhodopsin II	0.017	0.03	0.21	1	-0.3	4	5
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.019	0.098	-10000	0	-0.28	56	56
RGS9BP	0.02	0.038	0.36	1	-0.44	3	4
Metarhodopsin II/Transducin	-0.023	0.068	0.15	12	-0.23	13	25
GCAP Family/Ca ++	0.026	0.07	-10000	0	-0.25	37	37
PDE6A/B	-0.14	0.15	-10000	0	-0.26	355	355
mol:Pi	0.009	0.096	0.25	1	-0.21	94	95
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.033	0.13	0.23	14	-0.25	167	181
PDE6B	0.008	0.082	-10000	0	-0.36	28	28
PDE6A	-0.19	0.19	-10000	0	-0.36	346	346
PDE6G	0.005	0.089	-10000	0	-0.36	34	34
RHO	-0.017	0.032	-10000	0	-0.44	3	3
PDE6	-0.11	0.15	-10000	0	-0.36	90	90
GUCA1A	-0.011	0.11	0.36	1	-0.44	36	37
GC2/GCAP Family	0.035	0.076	-10000	0	-0.26	37	37
GUCA1C	-0.018	0.002	-10000	0	-10000	0	0
GUCA1B	0.028	0.03	0.36	3	-0.44	1	4

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.031	0.16	0.23	1	-0.4	58	59
PTK2B	0.02	0.025	-10000	0	-0.36	2	2
mol:Ca2+	-0.01	0.23	-10000	0	-0.82	36	36
EDN1	0.019	0.12	-10000	0	-0.27	26	26
EDN3	-0.1	0.17	-10000	0	-0.36	186	186
EDN2	-0.085	0.17	-10000	0	-0.36	175	175
HRAS/GDP	-0.002	0.15	0.34	7	-0.42	24	31
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.01	0.11	0.2	2	-0.38	18	20
ADCY4	-0.041	0.13	-10000	0	-0.37	50	50
ADCY5	-0.11	0.16	-10000	0	-0.38	115	115
ADCY6	-0.042	0.13	-10000	0	-0.37	50	50
ADCY7	-0.042	0.13	0.2	1	-0.37	50	51
ADCY1	-0.044	0.13	0.38	1	-0.38	48	49
ADCY2	-0.066	0.16	-10000	0	-0.39	77	77
ADCY3	-0.042	0.13	-10000	0	-0.37	51	51
ADCY8	-0.044	0.12	0.22	1	-0.37	43	44
ADCY9	-0.043	0.13	-10000	0	-0.37	50	50
arachidonic acid secretion	-0.025	0.16	0.3	9	-0.45	36	45
ETB receptor/Endothelin-1/Gq/GTP	0.007	0.072	-10000	0	-0.34	12	12
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
HRAS	0.027	0.016	-10000	0	-0.36	1	1
ETA receptor/Endothelin-1/G12/GTP	0.061	0.2	0.3	5	-0.38	45	50
ETA receptor/Endothelin-1/Gs/GTP	0.033	0.19	0.29	3	-0.36	61	64
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.034	0.18	-10000	0	-0.45	57	57
EDNRB	0.009	0.063	-10000	0	-0.36	15	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.041	0.19	0.26	1	-0.54	54	55
CYSLTR1	-0.069	0.23	0.23	1	-0.51	114	115
SLC9A1	-0.008	0.1	-10000	0	-0.25	56	56
mol:GDP	-0.013	0.15	0.27	16	-0.42	31	47
SLC9A3	-0.19	0.31	-10000	0	-0.59	152	152
RAF1	-0.015	0.13	0.3	8	-0.45	17	25
JUN	0.01	0.16	-10000	0	-0.61	13	13
JAK2	-0.031	0.16	0.22	2	-0.39	61	63
mol:IP3	0.02	0.11	0.21	9	-0.46	10	19
ETA receptor/Endothelin-1	0.042	0.25	0.34	5	-0.43	71	76
PLCB1	0.024	0.026	0.36	3	-10000	0	3
PLCB2	0.026	0.008	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.08	0.16	-10000	0	-0.28	199	199
FOS	-0.015	0.16	0.36	3	-0.83	13	16
Gai/GDP	-0.22	0.35	-10000	0	-0.66	226	226
CRK	0.024	0.01	-10000	0	-10000	0	0
mol:Ca ++	-0.009	0.15	0.23	9	-0.41	41	50
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
PRKCB1	0.017	0.1	0.22	10	-0.44	10	20
GNAQ	0.026	0.025	-10000	0	-0.36	2	2
GNAZ	0.023	0.035	-10000	0	-0.36	5	5
GNAL	0.008	0.073	-10000	0	-0.36	23	23
Gs family/GDP	-0.015	0.14	0.3	5	-0.4	31	36
ETA receptor/Endothelin-1/Gq/GTP	0.006	0.12	0.25	1	-0.41	14	15
MAPK14	0.008	0.074	0.21	1	-0.43	7	8
TRPC6	-0.013	0.24	-10000	0	-0.89	36	36
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.015	0.067	-10000	0	-0.36	19	19
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.011	0.078	-10000	0	-0.4	9	9
ETB receptor/Endothelin-2	-0.037	0.12	-10000	0	-0.26	138	138
ETB receptor/Endothelin-3	-0.065	0.13	-10000	0	-0.26	174	174
ETB receptor/Endothelin-1	0.021	0.099	-10000	0	-0.32	15	15
MAPK3	-0.013	0.14	0.34	5	-0.66	14	19
MAPK1	-0.018	0.16	0.36	4	-0.69	17	21
Rac1/GDP	-0.006	0.14	0.31	7	-0.4	29	36
cAMP biosynthetic process	-0.088	0.15	0.24	1	-0.38	79	80
MAPK8	0.006	0.18	0.34	1	-0.6	34	35
SRC	0.017	0.014	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.046	0.13	-10000	0	-0.33	61	61
p130Cas/CRK/Src/PYK2	-0.013	0.18	0.32	22	-0.54	34	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.006	0.14	0.34	5	-0.41	26	31
COL1A2	-0.002	0.17	0.24	1	-0.39	56	57
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.074	0.18	-10000	0	-0.3	199	199
mol:DAG	0.02	0.11	0.21	9	-0.46	10	19
MAP2K2	-0.016	0.13	0.34	6	-0.52	16	22
MAP2K1	-0.015	0.13	0.31	6	-0.52	16	22
EDNRA	-0.013	0.17	-10000	0	-0.38	73	73
positive regulation of muscle contraction	-0.012	0.15	0.25	28	-0.37	41	69
Gq family/GDP	-0.004	0.13	-10000	0	-0.46	15	15
HRAS/GTP	-0.016	0.13	0.31	7	-0.4	25	32
PRKCH	0.016	0.1	0.2	9	-0.48	8	17
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.017	0.11	0.22	14	-0.48	8	22
PRKCB	-0.017	0.14	0.21	10	-0.36	51	61
PRKCE	0.017	0.1	0.21	10	-0.48	8	18
PRKCD	0.015	0.1	0.2	9	-0.46	9	18
PRKCG	-0.053	0.15	0.24	12	-0.39	38	50
regulation of vascular smooth muscle contraction	-0.02	0.18	0.45	2	-0.97	13	15
PRKCQ	0.015	0.11	0.22	11	-0.43	13	24
PLA2G4A	-0.029	0.17	0.32	7	-0.49	36	43
GNA14	0.024	0.037	-10000	0	-0.36	5	5
GNA15	0.022	0.047	-10000	0	-0.44	6	6
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA11	0.024	0.033	-10000	0	-0.36	4	4
Rac1/GTP	0.061	0.2	0.3	5	-0.36	53	58
MMP1	-0.2	0.18	0.27	2	-0.35	312	314

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.01	0.066	-10000	0	-0.26	34	34
EPHB2	0.024	0.033	-10000	0	-0.44	3	3
Syndecan-2/TACI	-0.053	0.1	-10000	0	-0.21	192	192
LAMA1	-0.054	0.15	-10000	0	-0.36	121	121
Syndecan-2/alpha2 ITGB1	0.041	0.034	-10000	0	-0.23	1	1
HRAS	0.027	0.016	-10000	0	-0.36	1	1
Syndecan-2/CASK	0.007	0.012	-10000	0	-0.2	2	2
ITGA5	0.026	0.027	-10000	0	-0.44	2	2
BAX	0.004	0.011	-10000	0	-10000	0	0
EPB41	0.026	0.007	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.022	0.017	-10000	0	-0.18	3	3
LAMA3	0.02	0.034	-10000	0	-0.38	4	4
EZR	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.023	0.04	-10000	0	-0.41	5	5
Syndecan-2/MMP2	0.022	0.035	-10000	0	-0.26	8	8
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.04	0.006	-10000	0	-10000	0	0
dendrite morphogenesis	0.022	0.026	-10000	0	-0.24	5	5
Syndecan-2/GM-CSF	-0.076	0.14	-10000	0	-0.26	223	223
determination of left/right symmetry	0.01	0.015	-10000	0	-0.24	2	2
Syndecan-2/PKC delta	0.025	0.017	-10000	0	-0.2	2	2
GNB2L1	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.067	0.14	0.19	45	-0.24	221	266
MAPK1	-0.067	0.14	0.19	46	-0.24	222	268
Syndecan-2/RACK1	0.036	0.022	-10000	0	-0.17	3	3
NF1	0.027	0.005	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.01	0.015	-10000	0	-0.24	2	2
ITGA2	0.027	0.004	-10000	0	-10000	0	0
MAPK8	0.009	0.013	-10000	0	-0.2	2	2
Syndecan-2/alpha2/beta1 Integrin	0.002	0.086	-10000	0	-10000	0	0
Syndecan-2/Kininogen	-0.019	0.089	-10000	0	-0.2	114	114
ITGB1	0.028	0.002	-10000	0	-10000	0	0
SRC	0.015	0.037	0.18	25	-10000	0	25
Syndecan-2/CASK/Protein 4.1	0.021	0.016	-10000	0	-0.18	2	2
extracellular matrix organization	0.024	0.02	-10000	0	-0.22	3	3
actin cytoskeleton reorganization	0.01	0.066	-10000	0	-0.26	34	34
Syndecan-2/Caveolin-2/Ras	0.036	0.03	-10000	0	-0.21	6	6
Syndecan-2/Laminin alpha3	0.019	0.023	-10000	0	-0.21	4	4
Syndecan-2/RasGAP	0.046	0.026	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.04	0.021	-10000	0	-0.32	2	2
PRKCD	0.027	0.004	-10000	0	-10000	0	0
Syndecan-2 dimer	0.022	0.027	-10000	0	-0.24	5	5
GO:0007205	0.002	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.02	0.024	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
SDCBP	0.024	0.018	-10000	0	-0.36	1	1
TNFRSF13B	-0.12	0.18	-10000	0	-0.36	214	214
RASA1	0.027	0.005	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.04	0.006	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0.025	0.017	-10000	0	-0.2	2	2
TGFB1	0.027	0.019	-10000	0	-0.44	1	1
CASP3	0.033	0.058	0.19	68	-0.18	2	70
FN1	0.001	0.11	-10000	0	-0.43	36	36
Syndecan-2/IL8	-0.11	0.15	-10000	0	-0.26	297	297
SDC2	0.01	0.015	-10000	0	-0.24	2	2
KNG1	-0.062	0.15	-10000	0	-0.36	128	128
Syndecan-2/Neurofibromin	0.024	0.017	-10000	0	-0.2	2	2
TRAPPC4	0.027	0.004	-10000	0	-10000	0	0
CSF2	-0.17	0.23	-10000	0	-0.45	250	250
Syndecan-2/TGFB1	0.024	0.021	-10000	0	-0.22	3	3
Syndecan-2/Syntenin/PI-4-5-P2	0.022	0.017	-10000	0	-0.18	3	3
Syndecan-2/Ezrin	0.038	0.022	-10000	0	-0.19	2	2
PRKACA	0.036	0.061	0.19	77	-0.18	2	79
angiogenesis	-0.11	0.15	-10000	0	-0.26	297	297
MMP2	0.022	0.05	-10000	0	-0.41	8	8
IL8	-0.23	0.24	0.36	2	-0.44	338	340
calcineurin-NFAT signaling pathway	-0.053	0.1	-10000	0	-0.21	192	192

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.034	0.096	-10000	0	-0.24	57	57
MAP4K1	-0.006	0.11	-10000	0	-0.36	53	53
MAP3K8	0.028	0.002	-10000	0	-10000	0	0
PRKCB	-0.062	0.16	-10000	0	-0.36	141	141
DBNL	0.025	0.008	-10000	0	-10000	0	0
CRKL	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	-0.006	0.089	-10000	0	-0.32	30	30
JUN	-0.13	0.27	-10000	0	-0.58	156	156
MAP3K7	-0.006	0.089	-10000	0	-0.32	31	31
GRAP2	0.014	0.069	-10000	0	-0.36	20	20
CRK	0.023	0.01	-10000	0	-10000	0	0
MAP2K4	-0.014	0.1	0.25	3	-0.36	35	38
LAT	0.025	0.035	-10000	0	-0.4	4	4
LCP2	0.023	0.038	-10000	0	-0.36	6	6
MAPK8	-0.13	0.29	-10000	0	-0.61	156	156
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.001	0.096	-10000	0	-0.33	32	32
LAT/GRAP2/SLP76/HPK1/HIP-55	0.041	0.091	-10000	0	-0.35	11	11

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.035	0.052	-10000	0	-0.21	24	24
RGS9BP	0.02	0.038	0.36	1	-0.44	3	4
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.01	0.032	0.36	1	-0.44	2	3
mol:Na +	-0.052	0.12	0.23	6	-0.23	192	198
mol:ADP	-0.013	0.035	0.27	1	-0.38	4	5
GNAT2	0.013	0.068	-10000	0	-0.44	13	13
RGS9-1/Gbeta5/R9AP	0.009	0.096	0.25	1	-0.21	94	95
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.022	0.044	-10000	0	-0.27	13	13
GRK7	0.009	0.043	-10000	0	-0.44	4	4
CNGB3	-0.017	0.099	0.36	8	-0.44	25	33
Cone Metarhodopsin II/X-Arrestin	0.013	0.023	-10000	0	-0.31	3	3
mol:Ca2+	-0.069	0.14	0.18	50	-0.3	64	114
Cone PDE6	0.023	0.094	0.25	1	-0.24	4	5
Cone Metarhodopsin II	0.02	0.031	0.22	1	-0.3	4	5
Na + (4 Units)	-0.057	0.14	0.23	6	-0.23	216	222
GNAT2/GDP	0.015	0.095	0.24	1	-0.25	15	16
GNB5	0.026	0.006	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.018	0.039	0.18	5	-0.25	13	18
Cone Transducin	0.038	0.055	-10000	0	-0.22	24	24
SLC24A2	-0.027	0.13	0.36	5	-0.44	52	57
GNB3/GNGT2	0.033	0.044	-10000	0	-0.27	12	12
GNB3	0.024	0.037	-10000	0	-0.42	4	4
GNAT2/GTP	0.012	0.048	-10000	0	-0.31	13	13
CNGA3	-0.11	0.18	-10000	0	-0.36	199	199
ARR3	-0.008	0.037	-10000	0	-0.44	3	3
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.052	0.12	0.23	6	-0.23	192	198
mol:Pi	0.009	0.096	0.25	1	-0.21	94	95
Cone CNG Channel	-0.037	0.12	-10000	0	-0.28	33	33
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	-0.027	0.13	0.36	5	-0.44	52	57
RGS9	-0.033	0.14	-10000	0	-0.36	93	93
PDE6C	-0.005	0.02	-10000	0	-10000	0	0
GNGT2	0.022	0.044	-10000	0	-0.36	8	8
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.015	0.021	-10000	0	-0.44	1	1

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.028	0.085	-10000	0	-0.26	14	14
ER alpha/Gai/GDP/Gbeta gamma	-0.14	0.26	-10000	0	-0.57	112	112
AKT1	-0.063	0.28	-10000	0	-0.81	70	70
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.062	0.28	-10000	0	-0.83	70	70
mol:Ca2+	0.02	0.071	-10000	0	-0.38	7	7
IGF1R	0.027	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.014	0.071	-10000	0	-0.21	55	55
SHC1	0.027	0.004	-10000	0	-10000	0	0
apoptosis	0.059	0.26	0.77	70	-10000	0	70
RhoA/GTP	0.007	0.056	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.043	0.22	0.21	1	-0.52	71	72
regulation of stress fiber formation	0.017	0.054	0.27	2	-0.3	1	3
E2/ERA-ERB (dimer)	0.011	0.073	-10000	0	-0.21	59	59
KRAS	0.026	0.016	-10000	0	-0.36	1	1
G13/GTP	0.014	0.063	-10000	0	-0.19	54	54
pseudopodium formation	-0.017	0.054	0.3	1	-0.27	2	3
E2/ER alpha (dimer)/PELP1	0.011	0.067	-10000	0	-0.2	55	55
GRB2	0.027	0.004	-10000	0	-10000	0	0
GNG2	0.011	0.074	-10000	0	-0.36	23	23
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
HRAS	0.027	0.016	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.084	0.23	0.21	3	-0.59	81	84
E2/ER beta (dimer)	0.017	0.025	-10000	0	-0.25	5	5
mol:GDP	-0.016	0.099	-10000	0	-0.31	57	57
mol:NADP	-0.084	0.23	0.21	3	-0.59	81	84
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	0.002	0.051	-10000	0	-0.4	7	7
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
PLCB1	0.006	0.055	0.17	3	-0.41	7	10
PLCB2	0.006	0.056	-10000	0	-0.41	8	8
IGF1	-0.062	0.16	-10000	0	-0.36	141	141
mol:L-citrulline	-0.084	0.23	0.21	3	-0.59	81	84
RHOA	0.027	0.004	-10000	0	-10000	0	0
Gai/GDP	-0.23	0.35	-10000	0	-0.66	234	234
JNK cascade	0.017	0.025	-10000	0	-0.25	5	5
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
ESR2	0.022	0.036	-10000	0	-0.36	5	5
GNAQ	0.026	0.022	-10000	0	-0.36	2	2
ESR1	-0.009	0.11	-10000	0	-0.36	55	55
Gq family/GDP/Gbeta gamma	-0.004	0.14	-10000	0	-0.65	19	19
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.004	0.13	-10000	0	-0.6	14	14
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.042	0.21	-10000	0	-0.52	70	70
GNAZ	0.023	0.035	-10000	0	-0.36	5	5
E2/ER alpha (dimer)	-0.004	0.077	-10000	0	-0.25	55	55
STRN	0.028	0.003	-10000	0	-10000	0	0
GNAL	0.008	0.073	-10000	0	-0.36	23	23
PELP1	0.023	0.01	-10000	0	-10000	0	0
MAPK11	0.01	0.026	-10000	0	-0.23	7	7
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.015	0.067	-10000	0	-0.36	19	19
HBEGF	-0.021	0.26	0.31	133	-0.53	74	207
cAMP biosynthetic process	0	0.07	-10000	0	-0.19	59	59
SRC	-0.066	0.25	0.21	109	-0.59	78	187
PI3K	0.039	0.015	-10000	0	-0.25	1	1
GNB1	0.026	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.008	0.11	-10000	0	-0.29	52	52
SOS1	0.028	0.002	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.095	0.17	-10000	0	-0.41	106	106
Gs family/GTP	0.005	0.074	-10000	0	-0.19	59	59
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.024	-10000	0	-0.19	4	4
vasodilation	-0.079	0.21	0.21	3	-0.56	81	84
mol:DAG	0.002	0.051	-10000	0	-0.4	7	7
Gs family/GDP/Gbeta gamma	-0.016	0.1	-10000	0	-0.3	53	53
MSN	-0.019	0.057	0.31	1	-0.28	2	3
Gq family/GTP	0.013	0.062	-10000	0	-0.43	8	8
mol:PI-3-4-5-P3	-0.058	0.27	-10000	0	-0.79	70	70
NRAS	0.026	0.023	-10000	0	-0.36	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.079	0.21	0.56	81	-0.21	3	84
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.1	-10000	0	-0.3	53	53
NOS3	-0.09	0.24	0.22	2	-0.63	81	83
GNA11	0.025	0.031	-10000	0	-0.36	4	4
MAPKKK cascade	-0.04	0.22	0.3	2	-0.61	69	71
E2/ER alpha (dimer)/PELP1/Src	-0.043	0.23	0.24	12	-0.53	75	87
ruffle organization	-0.017	0.054	0.3	1	-0.27	2	3
ROCK2	-0.018	0.061	0.32	1	-0.31	2	3
GNA14	0.024	0.035	-10000	0	-0.36	5	5
GNA15	0.023	0.046	-10000	0	-0.44	6	6
GNA13	0.027	0.005	-10000	0	-10000	0	0
MMP9	-0.025	0.26	0.37	111	-0.53	74	185
MMP2	-0.064	0.24	0.27	9	-0.56	76	85

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.01	0.098	-10000	0	-0.32	15	15
NF kappa B1 p50/RelA/I kappa B alpha	-0.004	0.09	0.31	2	-0.36	3	5
AP1	-0.031	0.085	-10000	0	-0.3	15	15
mol:PIP3	-0.026	0.073	-10000	0	-0.3	11	11
AKT1	0.005	0.076	0.24	5	-0.4	3	8
PTK2B	-0.051	0.11	0.2	2	-0.31	49	51
RHOA	0.008	0.064	0.23	6	-0.33	12	18
PIK3CB	0.028	0.014	0.36	1	-10000	0	1
mol:Ca2+	-0.001	0.055	0.2	5	-0.33	2	7
MAGI3	0.026	0.016	-10000	0	-0.36	1	1
RELA	0.027	0.004	-10000	0	-10000	0	0
apoptosis	-0.028	0.097	-10000	0	-0.22	110	110
HRAS/GDP	0.02	0.011	-10000	0	-0.25	1	1
positive regulation of microtubule depolymerization	-0.081	0.12	0.23	5	-0.32	75	80
NF kappa B1 p50/RelA	-0.032	0.082	-10000	0	-0.35	9	9
endothelial cell migration	-0.014	0.088	-10000	0	-0.44	8	8
ADCY4	-0.084	0.17	0.24	1	-0.42	100	101
ADCY5	-0.17	0.23	0.24	1	-0.45	201	202
ADCY6	-0.08	0.16	0.24	1	-0.44	87	88
ADCY7	-0.079	0.16	0.24	1	-0.44	85	86
ADCY1	-0.08	0.16	-10000	0	-0.43	86	86
ADCY2	-0.11	0.21	0.24	1	-0.46	132	133
ADCY3	-0.08	0.16	0.24	1	-0.44	87	88
ADCY8	-0.076	0.16	0.24	1	-0.43	82	83
ADCY9	-0.08	0.16	0.24	1	-0.43	88	89
GSK3B	-0.049	0.11	0.2	2	-0.36	29	31
arachidonic acid secretion	-0.099	0.18	-10000	0	-0.44	96	96
GNG2	0.011	0.074	-10000	0	-0.36	23	23
TRIP6	0.012	0.019	-10000	0	-0.3	1	1
GNAO1	-0.089	0.14	-10000	0	-0.25	241	241
HRAS	0.027	0.016	-10000	0	-0.36	1	1
NFKBIA	-0.021	0.089	0.3	3	-0.34	8	11
GAB1	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.089	0.32	-10000	0	-0.84	94	94
JUN	0.027	0.004	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.035	0.021	-10000	0	-0.24	2	2
TIAM1	-0.12	0.37	-10000	0	-0.99	94	94
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	-0.01	0.052	0.21	5	-0.34	2	7
PLCB3	0.016	0.025	0.18	8	-0.21	2	10
FOS	0.022	0.039	-10000	0	-0.36	6	6
positive regulation of mitosis	-0.099	0.18	-10000	0	-0.44	96	96
LPA/LPA1-2-3	0.001	0.1	-10000	0	-0.31	17	17
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	-0.001	0.001	-10000	0	-10000	0	0
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
stress fiber formation	-0.028	0.093	0.22	3	-0.29	27	30
GNAZ	-0.013	0.08	-10000	0	-0.21	79	79
EGFR/PI3K-beta/Gab1	-0.012	0.082	-10000	0	-0.31	11	11
positive regulation of dendritic cell cytokine production	0	0.1	-10000	0	-0.31	17	17
LPA/LPA2/MAGI-3	0.036	0.021	-10000	0	-0.23	2	2
ARHGEF1	0.008	0.089	0.33	5	-0.33	2	7
GNAI2	-0.01	0.076	-10000	0	-0.21	63	63
GNAI3	-0.012	0.078	-10000	0	-0.21	80	80
GNAI1	-0.018	0.091	-10000	0	-0.23	85	85
LPA/LPA3	-0.001	0.072	-10000	0	-0.26	44	44
LPA/LPA2	0.02	0.018	-10000	0	-0.31	1	1
LPA/LPA1	-0.012	0.095	-10000	0	-0.24	86	86
HB-EGF/EGFR	0.004	0.072	0.2	14	-0.26	34	48
HBEGF	-0.004	0.086	0.27	15	-0.31	34	49
mol:DAG	-0.01	0.052	0.21	5	-0.34	2	7
cAMP biosynthetic process	-0.11	0.18	0.27	5	-0.47	86	91
NFKB1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
LYN	-0.003	0.091	0.28	7	-0.35	6	13
GNAQ	-0.001	0.058	-10000	0	-0.2	47	47
LPAR2	0.026	0.019	-10000	0	-0.44	1	1
LPAR3	-0.009	0.1	-10000	0	-0.37	44	44
LPAR1	-0.022	0.13	-10000	0	-0.36	80	80
IL8	-0.085	0.14	0.32	2	-0.39	15	17
PTK2	-0.021	0.079	-10000	0	-0.34	8	8
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
CASP3	-0.028	0.098	-10000	0	-0.22	110	110
EGFR	0.023	0.023	-10000	0	-0.36	2	2
PLCG1	-0.008	0.053	-10000	0	-0.2	37	37
PLD2	-0.022	0.081	-10000	0	-0.33	10	10
G12/G13	0.02	0.082	-10000	0	-0.35	2	2
PI3K-beta	-0.004	0.073	-10000	0	-0.38	6	6
cell migration	-0.017	0.11	-10000	0	-0.25	87	87
SLC9A3R2	0.026	0.016	-10000	0	-0.36	1	1
PXN	-0.028	0.095	0.22	3	-0.29	27	30
HRAS/GTP	-0.1	0.18	-10000	0	-0.45	97	97
RAC1	0.025	0.008	-10000	0	-10000	0	0
MMP9	0	0.12	0.36	15	-0.44	32	47
PRKCE	0.027	0.003	-10000	0	-10000	0	0
PRKCD	-0.003	0.058	0.24	7	-0.4	1	8
Gi(beta/gamma)	-0.085	0.17	-10000	0	-0.41	100	100
mol:LPA	0.001	0.014	-10000	0	-0.13	6	6
TRIP6/p130 Cas/FAK1/Paxillin	0.01	0.1	0.23	1	-0.36	10	11
MAPKKK cascade	-0.099	0.18	-10000	0	-0.44	96	96
contractile ring contraction involved in cytokinesis	0.01	0.065	0.23	6	-0.33	12	18
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.002	0.06	-10000	0	-0.2	50	50
GNA15	-0.002	0.059	-10000	0	-0.19	51	51
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.083	0.12	0.24	4	-0.33	75	79
GNA11	-0.001	0.058	-10000	0	-0.2	49	49
Rac1/GTP	-0.095	0.34	-10000	0	-0.89	94	94
MMP2	-0.014	0.089	-10000	0	-0.44	8	8

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.008	0.14	-9999	-0.53	25	25
MAP3K8	0.028	0.003	-9999	-10000	0	0
FOS	-0.022	0.14	-9999	-0.53	25	25
PRKCA	0.027	0.007	-9999	-10000	0	0
PTPN7	0.017	0.066	-9999	-0.41	14	14
HRAS	0.027	0.016	-9999	-0.36	1	1
PRKCB	-0.062	0.16	-9999	-0.36	141	141
NRAS	0.026	0.023	-9999	-0.36	2	2
RAS family/GTP	0.049	0.024	-9999	-0.19	4	4
MAPK3	-0.002	0.097	-9999	-0.6	9	9
MAP2K1	-0.057	0.16	-9999	-0.34	134	134
ELK1	0.027	0.007	-9999	-10000	0	0
BRAF	-0.052	0.14	-9999	-0.33	124	124
mol:GTP	0	0	-9999	-0.004	10	10
MAPK1	-0.022	0.15	-9999	-0.58	32	32
RAF1	-0.056	0.15	-9999	-0.33	135	135
KRAS	0.026	0.016	-9999	-0.36	1	1

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0	0.15	0.27	9	-0.48	39	48
FYN	-0.027	0.18	0.21	8	-0.54	53	61
LAT/GRAP2/SLP76	-0.006	0.16	0.19	2	-0.49	45	47
IKBKB	0.024	0.009	-10000	0	-10000	0	0
AKT1	-0.022	0.13	0.19	6	-0.39	55	61
B2M	0.025	0.018	-10000	0	-0.36	1	1
IKBKG	-0.002	0.045	0.088	27	-0.14	19	46
MAP3K8	0.028	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.032	0.088	5	-0.11	53	58
integrin-mediated signaling pathway	0.033	0.025	-10000	0	-0.2	6	6
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.035	0.19	0.22	4	-0.55	56	60
TRPV6	-0.002	0.26	1.2	22	-0.44	52	74
CD28	0.012	0.078	-10000	0	-0.36	25	25
SHC1	-0.027	0.18	0.27	10	-0.51	54	64
receptor internalization	-0.034	0.2	-10000	0	-0.56	58	58
PRF1	-0.032	0.22	-10000	0	-0.84	31	31
KRAS	0.026	0.016	-10000	0	-0.36	1	1
GRB2	0.027	0.004	-10000	0	-10000	0	0
COT/AKT1	-0.005	0.11	0.19	6	-0.32	49	55
LAT	-0.03	0.18	0.19	4	-0.51	55	59
EntrezGene:6955	0	0.002	-10000	0	-10000	0	0
CD3D	0.017	0.063	-10000	0	-0.37	16	16
CD3E	0.014	0.072	-10000	0	-0.37	21	21
CD3G	-0.003	0.1	-10000	0	-0.36	47	47
RASGRP2	-0.01	0.055	-10000	0	-0.17	61	61
RASGRP1	-0.001	0.14	0.23	6	-0.4	48	54
HLA-A	0	0.003	-10000	0	-10000	0	0
RASSF5	0.023	0.038	-10000	0	-0.36	6	6
RAP1A/GTP/RAPL	0.033	0.025	-10000	0	-0.2	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.058	0.15	17	-0.12	37	54
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.018	0.063	-10000	0	-0.21	40	40
PRKCA	0.023	0.094	0.16	35	-0.26	32	67
GRAP2	0.014	0.069	-10000	0	-0.36	20	20
mol:IP3	-0.008	0.12	0.2	50	-0.39	37	87
EntrezGene:6957	0	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.026	0.16	-10000	0	-0.52	49	49
ORAI1	-0.013	0.2	-10000	0	-0.97	22	22
CSK	-0.026	0.17	0.22	3	-0.52	53	56
B7 family/CD28	-0.002	0.19	-10000	0	-0.59	46	46
CHUK	0.027	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.034	0.2	0.19	1	-0.57	58	59
PTPN6	-0.03	0.18	0.21	6	-0.51	55	61
VAV1	-0.035	0.18	0.23	4	-0.53	57	61
Monovalent TCR/CD3	-0.014	0.13	-10000	0	-0.36	58	58
CBL	0.027	0.004	-10000	0	-10000	0	0
LCK	-0.03	0.18	0.19	10	-0.52	57	67
PAG1	-0.018	0.18	0.19	49	-0.52	52	101
RAP1A	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.033	0.2	0.19	1	-0.57	57	58
CD80	0.024	0.035	-10000	0	-0.4	4	4
CD86	0.019	0.057	-10000	0	-0.36	13	13
PDK1/CARD11/BCL10/MALT1	-0.013	0.08	-10000	0	-0.25	41	41
HRAS	0.027	0.016	-10000	0	-0.36	1	1
GO:0035030	-0.027	0.15	0.16	1	-0.47	50	51
CD8A	-0.001	0.1	-10000	0	-0.37	45	45
CD8B	0.018	0.062	-10000	0	-0.37	15	15
PTPRC	-0.004	0.1	-10000	0	-0.36	48	48
PDK1/PKC theta	-0.018	0.16	0.23	8	-0.48	48	56
CSK/PAG1	-0.015	0.17	0.2	51	-0.53	45	96
SOS1	0.028	0.002	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.015	-10000	0	-0.25	1	1
GRAP2/SLP76	-0.007	0.18	0.2	3	-0.55	49	52
STIM1	0.008	0.11	1.2	4	-0.93	1	5
RAS family/GTP	0.022	0.068	0.15	15	-0.18	26	41
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.037	0.21	-10000	0	-0.6	58	58
mol:DAG	-0.021	0.098	0.12	1	-0.33	42	43
RAP1A/GDP	0.011	0.028	0.077	14	-0.063	13	27
PLCG1	0.016	0.014	-10000	0	-10000	0	0
CD247	0.018	0.059	-10000	0	-0.37	14	14
cytotoxic T cell degranulation	-0.029	0.21	-10000	0	-0.8	31	31
RAP1A/GTP	-0.004	0.021	-10000	0	-0.063	61	61
mol:PI-3-4-5-P3	-0.025	0.16	0.2	5	-0.46	54	59
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.01	0.15	0.22	44	-0.5	37	81
NRAS	0.026	0.023	-10000	0	-0.36	2	2
ZAP70	0.019	0.06	-10000	0	-0.37	14	14
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.015	0.16	0.21	1	-0.48	47	48
MALT1	0.02	0.02	-10000	0	-0.36	1	1
TRAF6	0.027	0.003	-10000	0	-10000	0	0
CD8 heterodimer	0.014	0.096	-10000	0	-0.29	52	52
CARD11	0.004	0.099	0.36	2	-0.41	31	33
PRKCB	0.001	0.12	0.15	29	-0.28	59	88
PRKCE	0.024	0.096	0.15	37	-0.26	33	70
PRKCQ	-0.021	0.18	0.24	4	-0.53	51	55
LCP2	0.023	0.038	-10000	0	-0.36	6	6
BCL10	0.026	0.016	-10000	0	-0.36	1	1
regulation of survival gene product expression	-0.017	0.12	0.19	6	-0.34	53	59
IKK complex	0.021	0.064	0.11	147	-0.11	28	175
RAS family/GDP	-0.002	0.011	-10000	0	-0.06	2	2
MAP3K14	-0.007	0.086	0.16	6	-0.25	45	51
PDPK1	-0.018	0.12	0.19	9	-0.38	48	57
TCR/CD3/MHC I/CD8/Fyn	-0.037	0.2	-10000	0	-0.58	58	58

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.028	0.001	-10000	0	-10000	0	0
PTK2	0.023	0.01	-10000	0	-10000	0	0
CRKL	-0.028	0.083	-10000	0	-0.19	129	129
GRB2/SOS1/SHC	0.054	0.012	-10000	0	-10000	0	0
HRAS	0.027	0.016	-10000	0	-0.36	1	1
IRS1/Crk	-0.023	0.087	-10000	0	-0.19	106	106
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.085	-10000	0	-0.2	88	88
AKT1	-0.043	0.068	0.2	3	-0.29	1	4
BAD	-0.043	0.065	0.19	3	-0.28	1	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.022	0.076	-10000	0	-0.19	103	103
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.018	0.093	-10000	0	-0.19	141	141
RAF1	-0.028	0.088	0.27	1	-0.46	9	10
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.007	0.1	-10000	0	-10000	0	0
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.019	0.1	-10000	0	-0.2	141	141
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
RPS6KB1	-0.043	0.068	0.2	3	-0.32	1	4
GNB2L1	0.027	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.011	0.082	0.25	4	-0.39	4	8
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
HRAS/GTP	-0.012	0.084	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.023	0.1	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.008	0.038	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.005	0.1	-10000	0	-0.19	141	141
Crk/p130 Cas/Paxillin	0.009	0.098	-10000	0	-10000	0	0
IGF1R	0.008	0.038	-10000	0	-10000	0	0
IGF1	-0.065	0.17	-10000	0	-0.38	141	141
IRS2/Crk	-0.015	0.073	-10000	0	-10000	0	0
PI3K	0.006	0.1	-10000	0	-0.34	1	1
apoptosis	0.035	0.057	-10000	0	-0.24	1	1
HRAS/GDP	0.02	0.011	-10000	0	-0.25	1	1
PRKCD	-0.055	0.13	-10000	0	-0.29	134	134
RAF1/14-3-3 E	-0.011	0.082	0.26	2	-0.38	10	12
BAD/14-3-3	-0.037	0.06	0.25	1	-10000	0	1
PRKCZ	-0.043	0.068	0.2	3	-0.32	1	4
Crk/p130 Cas/Paxillin/FAK1	-0.007	0.074	-10000	0	-10000	0	0
PTPN1	0.016	0.014	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.052	0.14	-10000	0	-0.3	143	143
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.011	0.097	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.028	0.002	-10000	0	-10000	0	0
IRS1/NCK2	-0.018	0.094	-10000	0	-0.19	141	141
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	-0.031	0.086	-10000	0	-0.19	141	141
IRS1	-0.034	0.093	-10000	0	-0.2	141	141
IRS2	-0.022	0.075	-10000	0	-0.19	103	103
IGF-1R heterotetramer/IGF1	-0.032	0.13	-10000	0	-0.27	141	141
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDPK1	-0.028	0.079	0.28	1	-0.33	1	2
YWHAE	0.023	0.01	-10000	0	-10000	0	0
PRKD1	-0.056	0.13	0.2	1	-0.3	133	134
SHC1	0.027	0.004	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.032	0.1	0.17	1	-0.3	44	45
FZD6	0.024	0.01	-10000	0	-10000	0	0
WNT6	-0.011	0.11	-10000	0	-0.38	52	52
WNT4	0.013	0.072	-10000	0	-0.38	20	20
FZD3	0.021	0.035	0.36	2	-0.44	2	4
WNT5A	0.022	0.05	-10000	0	-0.44	7	7
WNT11	-0.069	0.19	-10000	0	-0.44	127	127

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.008	0.073	0.26	3	-0.31	31	34
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.035	0.026	-10000	0	-0.32	3	3
STXBP1	0.022	0.05	-10000	0	-0.44	7	7
ACh/CHRNA1	-0.039	0.085	-10000	0	-0.21	77	77
RAB3GAP2/RIMS1/UNC13B	0.049	0.029	-10000	0	-0.26	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.009	0.042	-10000	0	-0.44	4	4
mol:ACh	-0.037	0.064	0.08	44	-0.11	212	256
RAB3GAP2	0.027	0.016	-10000	0	-0.36	1	1
STX1A/SNAP25/VAMP2	-0.038	0.1	-10000	0	-0.28	10	10
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.039	0.085	-10000	0	-0.21	77	77
UNC13B	0.027	0.004	-10000	0	-10000	0	0
CHRNA1	-0.008	0.11	-10000	0	-0.36	55	55
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.045	0.095	-10000	0	-0.23	95	95
SNAP25	-0.07	0.11	0.18	1	-0.24	188	189
VAMP2	0.004	0.002	-10000	0	-10000	0	0
SYT1	-0.02	0.13	-10000	0	-0.36	75	75
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.008	0.071	0.2	3	-0.27	35	38
STX1A/SNAP25 fragment 1/VAMP2	-0.038	0.1	-10000	0	-0.28	10	10

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.23	0.35	-10000	0	-1.1	48	48
IL23A	-0.27	0.35	-10000	0	-1.1	50	50
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.35	-10000	0	-1	56	56
positive regulation of T cell mediated cytotoxicity	-0.24	0.36	-10000	0	-1.1	55	55
ITGA3	-0.23	0.33	-10000	0	-1	42	42
IL17F	-0.21	0.26	-10000	0	-0.67	75	75
IL12B	-0.014	0.054	-10000	0	-0.47	4	4
STAT1 (dimer)	-0.23	0.35	-10000	0	-1	55	55
CD4	-0.23	0.36	-10000	0	-1.1	55	55
IL23	-0.26	0.34	-10000	0	-1	51	51
IL23R	-0.071	0.25	-10000	0	-1.1	32	32
IL1B	-0.26	0.36	-10000	0	-1.1	50	50
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.27	0.34	-10000	0	-0.99	60	60
TYK2	-0.004	0.033	-10000	0	-10000	0	0
STAT4	0.011	0.08	-10000	0	-0.36	27	27
STAT3	0.026	0.006	-10000	0	-10000	0	0
IL18RAP	0.006	0.083	-10000	0	-0.36	29	29
IL12RB1	-0.016	0.076	-10000	0	-0.39	20	20
PIK3CA	0.026	0.017	-10000	0	-0.36	1	1
IL12Rbeta1/TYK2	-0.01	0.066	-10000	0	-0.28	20	20
IL23R/JAK2	-0.072	0.24	-10000	0	-1	29	29
positive regulation of chronic inflammatory response	-0.24	0.36	-10000	0	-1.1	55	55
natural killer cell activation	0.005	0.013	0.079	15	-10000	0	15
JAK2	-0.008	0.047	-10000	0	-0.38	3	3
PIK3R1	0.026	0.007	-10000	0	-10000	0	0
NFKB1	0.025	0.005	-10000	0	-10000	0	0
RELA	0.025	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.26	0.33	-10000	0	-0.98	51	51
ALOX12B	-0.22	0.33	-10000	0	-1	40	40
CXCL1	-0.27	0.35	-10000	0	-0.98	65	65
T cell proliferation	-0.24	0.36	-10000	0	-1.1	55	55
NFKBIA	0.024	0.007	-10000	0	-10000	0	0
IL17A	-0.2	0.23	-10000	0	-0.56	86	86
PI3K	-0.23	0.35	-10000	0	-1	58	58
IFNG	-0.01	0.036	0.14	13	-0.11	8	21
STAT3 (dimer)	-0.24	0.35	-10000	0	-0.97	59	59
IL18R1	0.019	0.05	-10000	0	-0.36	10	10
IL23/IL23R/JAK2/TYK2/SOCS3	-0.15	0.23	-10000	0	-0.73	43	43
IL18/IL18R	0.033	0.073	-10000	0	-0.22	31	31
macrophage activation	-0.017	0.017	-10000	0	-0.044	34	34
TNF	-0.25	0.35	-10000	0	-1.1	44	44
STAT3/STAT4	-0.23	0.35	-10000	0	-1	56	56
STAT4 (dimer)	-0.24	0.36	-10000	0	-1.1	57	57
IL18	0.023	0.03	-10000	0	-0.36	3	3
IL19	-0.22	0.32	-10000	0	-1	45	45
STAT5A (dimer)	-0.23	0.35	-10000	0	-1	53	53
STAT1	0.027	0.019	-10000	0	-0.44	1	1
SOCS3	0.026	0.027	-10000	0	-0.44	2	2
CXCL9	-0.24	0.34	-10000	0	-1	53	53
MPO	-0.22	0.32	-10000	0	-1	45	45
positive regulation of humoral immune response	-0.24	0.36	-10000	0	-1.1	55	55
IL23/IL23R/JAK2/TYK2	-0.25	0.38	-10000	0	-1.1	55	55
IL6	-0.24	0.36	-10000	0	-1.1	53	53
STAT5A	0.027	0.004	-10000	0	-10000	0	0
IL2	0.013	0.022	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.005	0.013	0.079	15	-10000	0	15
CD3E	-0.24	0.37	-10000	0	-1.1	66	66
keratinocyte proliferation	-0.24	0.36	-10000	0	-1.1	55	55
NOS2	-0.25	0.37	-10000	0	-1.1	58	58

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.036	0.24	0.39	3	-0.78	42	45
NCK1/PAK1/Dok-R	-0.029	0.099	-10000	0	-0.39	40	40
NCK1/Dok-R	0.007	0.26	-10000	0	-0.91	41	41
PIK3CA	0.026	0.016	-10000	0	-0.36	1	1
mol:beta2-estradiol	0.004	0.053	0.25	27	-10000	0	27
RELA	0.027	0.004	-10000	0	-10000	0	0
SHC1	0.028	0.005	-10000	0	-10000	0	0
Rac/GDP	0.019	0.006	-10000	0	-10000	0	0
F2	-0.14	0.23	0.27	27	-0.46	197	224
TNIP2	0.027	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	0.042	0.25	-10000	0	-0.85	42	42
FN1	0.001	0.11	-10000	0	-0.43	36	36
PLD2	-0.028	0.26	-10000	0	-0.93	42	42
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GRB14	-0.005	0.1	-10000	0	-0.39	42	42
ELK1	0.009	0.25	0.37	1	-0.85	43	44
GRB7	0.035	0.049	0.36	14	-10000	0	14
PAK1	0.027	0.004	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.031	0.27	-10000	0	-0.9	42	42
CDKN1A	0.038	0.19	0.41	5	-0.6	29	34
ITGA5	0.026	0.027	-10000	0	-0.44	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.007	0.26	-10000	0	-0.91	41	41
CRK	0.023	0.01	-10000	0	-10000	0	0
mol:NO	0.05	0.2	0.39	19	-0.59	43	62
PLG	-0.059	0.27	-10000	0	-0.96	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.026	0.23	-10000	0	-0.75	42	42
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
ANGPT2	-0.025	0.2	0.43	2	-0.74	15	17
BMX	-0.063	0.28	-10000	0	-1	42	42
ANGPT1	0.007	0.25	0.34	1	-1.1	28	29
tube development	0.027	0.21	0.4	10	-0.64	33	43
ANGPT4	0.012	0.039	-10000	0	-0.44	4	4
response to hypoxia	-0.003	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.007	0.29	-10000	0	-0.96	43	43
alpha5/beta1 Integrin	0.04	0.021	-10000	0	-0.32	2	2
FGF2	-0.001	0.099	-10000	0	-0.36	43	43
STAT5A (dimer)	0.035	0.23	0.43	1	-0.74	32	33
mol:L-citrulline	0.05	0.2	0.39	19	-0.59	43	62
AGTR1	-0.11	0.18	-10000	0	-0.36	214	214
MAPK14	-0.001	0.28	-10000	0	-0.97	43	43
Tie2/SHP2	0.019	0.2	-10000	0	-0.98	22	22
TEK	-0.007	0.22	-10000	0	-1.1	22	22
RPS6KB1	0.034	0.24	0.44	3	-0.75	43	46
Angiotensin II/AT1	-0.073	0.13	-10000	0	-0.25	214	214
Tie2/Ang1/GRB2	0.018	0.28	-10000	0	-0.96	42	42
MAPK3	-0.017	0.24	-10000	0	-0.86	42	42
MAPK1	-0.018	0.24	-10000	0	-0.86	42	42
Tie2/Ang1/GRB7	0.022	0.28	-10000	0	-0.95	42	42
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.024	0.26	-10000	0	-0.94	42	42
PI3K	0.022	0.27	-10000	0	-0.89	43	43
FES	-0.01	0.29	-10000	0	-0.98	43	43
Crk/Dok-R	0.003	0.26	-10000	0	-0.91	41	41
Tie2/Ang1/ABIN2	0.018	0.28	-10000	0	-0.95	43	43
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.044	0.22	0.37	5	-0.69	43	48
STAT5A	0.028	0.004	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.055	0.25	0.42	20	-0.74	41	61
Tie2/Ang2	-0.009	0.25	0.45	1	-0.88	32	33
Tie2/Ang1	-0.022	0.28	-10000	0	-1	42	42
FOXO1	0.061	0.24	0.41	19	-0.72	36	55
ELF1	0.021	0.029	-10000	0	-10000	0	0
ELF2	-0.021	0.26	-10000	0	-0.94	42	42
mol:Choline	-0.026	0.25	-10000	0	-0.89	42	42
cell migration	-0.014	0.06	-10000	0	-0.22	42	42
FYN	0.021	0.23	0.44	5	-0.74	32	37
DOK2	0.016	0.045	-10000	0	-0.36	8	8
negative regulation of cell cycle	0.041	0.18	0.37	14	-0.55	29	43
ETS1	0.02	0.064	-10000	0	-0.27	27	27
PXN	0.06	0.22	0.39	33	-0.62	41	74
ITGB1	0.028	0.002	-10000	0	-10000	0	0
NOS3	0.046	0.22	0.4	15	-0.67	42	57
RAC1	0.025	0.008	-10000	0	-10000	0	0
TNF	0.019	0.07	-10000	0	-0.28	29	29
MAPKKK cascade	-0.026	0.25	-10000	0	-0.89	42	42
RASA1	0.027	0.005	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.02	0.28	-10000	0	-0.96	42	42
NCK1	0.028	0.002	-10000	0	-10000	0	0
vasculogenesis	0.053	0.19	0.36	27	-0.53	43	70
mol:Phosphatidic acid	-0.026	0.25	-10000	0	-0.89	42	42
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.05	0.2	0.39	19	-0.59	43	62
Rac1/GTP	0.03	0.22	-10000	0	-0.71	41	41
MMP2	-0.026	0.26	-10000	0	-0.94	42	42

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.006	0.002	-10000	0	-10000	0	0
ADCY5	-0.097	0.1	-10000	0	-0.21	272	272
ADCY6	-0.006	0.001	-10000	0	-10000	0	0
ADCY7	-0.006	0.001	-10000	0	-10000	0	0
ADCY1	-0.011	0.039	0.21	2	-0.26	14	16
ADCY2	-0.035	0.071	-10000	0	-0.21	85	85
ADCY3	-0.006	0.001	-10000	0	-10000	0	0
ADCY8	-0.012	0.031	0.21	1	-0.27	8	9
PRKCE	0.007	0.001	-10000	0	-10000	0	0
ADCY9	-0.007	0.012	-10000	0	-0.21	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.017	0.075	0.19	19	-0.2	5	24

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.078	0.13	-10000	0	-0.28	36	36
NF kappa B1 p50/RelA/I kappa B alpha	-0.063	0.13	0.31	6	-0.33	3	9
alphaV/beta3 Integrin/Osteopontin/Src	-0.11	0.18	-10000	0	-0.31	263	263
AP1	-0.06	0.14	-10000	0	-0.46	7	7
ILK	-0.088	0.13	-10000	0	-0.28	34	34
bone resorption	-0.073	0.12	0.33	1	-0.35	4	5
PTK2B	0.02	0.025	-10000	0	-0.36	2	2
PYK2/p130Cas	-0.06	0.14	-10000	0	-0.32	10	10
ITGAV	0.03	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.04	0.017	-10000	0	-0.25	2	2
alphaV/beta3 Integrin/Osteopontin	-0.082	0.16	-10000	0	-0.26	259	259
MAP3K1	-0.091	0.13	-10000	0	-0.29	36	36
JUN	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.093	0.12	0.19	1	-0.32	37	38
MAPK1	-0.092	0.12	0.19	1	-0.31	36	37
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.09	0.12	0.19	7	-0.28	35	42
ITGB3	0.025	0.041	-10000	0	-0.36	7	7
NFKBIA	-0.083	0.11	-10000	0	-0.31	37	37
FOS	0.022	0.039	-10000	0	-0.36	6	6
CD44	0.027	0.003	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
PLAU	-0.08	0.14	-10000	0	-0.47	7	7
NF kappa B1 p50/RelA	-0.061	0.14	-10000	0	-0.34	6	6
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
RELA	0.027	0.004	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.04	0.033	-10000	0	-0.25	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.09	0.13	-10000	0	-0.28	36	36
VAV3	-0.1	0.13	0.19	7	-0.33	65	72
MAP3K14	-0.092	0.13	-10000	0	-0.3	36	36
ROCK2	0.026	0.022	-10000	0	-0.36	2	2
SPP1	-0.17	0.23	-10000	0	-0.44	263	263
RAC1	0.025	0.008	-10000	0	-10000	0	0
Rac1/GTP	-0.085	0.13	-10000	0	-0.34	41	41
MMP2	-0.072	0.11	-10000	0	-0.53	7	7

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.019	0.091	-10000	0	-0.28	37	37
alphaM/beta2 Integrin/GPIbA	0.012	0.085	-10000	0	-0.35	14	14
alphaM/beta2 Integrin/proMMP-9	0.003	0.1	0.25	15	-0.3	36	51
PLAUR	0.027	0.004	-10000	0	-10000	0	0
HMGB1	0.015	0.022	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.022	0.083	-10000	0	-0.37	12	12
AGER	0.018	0.033	-10000	0	-0.49	1	1
RAP1A	0.027	0.005	-10000	0	-10000	0	0
SELPLG	0.026	0.022	-10000	0	-0.36	2	2
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.021	0.094	-10000	0	-0.39	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0	0.12	0.36	15	-0.44	32	47
CYR61	0.022	0.046	-10000	0	-0.44	6	6
TLN1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP	-0.022	0.1	-10000	0	-0.32	23	23
RHOA	0.027	0.004	-10000	0	-10000	0	0
P-selectin oligomer	-0.019	0.12	-10000	0	-0.36	72	72
MYH2	-0.038	0.095	-10000	0	-0.32	19	19
MST1R	0.027	0.016	-10000	0	-0.36	1	1
leukocyte activation during inflammatory response	-0.02	0.12	-10000	0	-0.27	66	66
APOB	-0.046	0.14	-10000	0	-0.38	92	92
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.022	0.05	-10000	0	-0.41	8	8
JAM3	0.027	0.004	-10000	0	-10000	0	0
GP1BA	0.014	0.043	-10000	0	-0.36	7	7
alphaM/beta2 Integrin/CTGF	0.02	0.086	-10000	0	-0.35	15	15
alphaM/beta2 Integrin	-0.037	0.1	-10000	0	-0.3	41	41
JAM3 homodimer	0.027	0.004	-10000	0	-10000	0	0
ICAM2	0.027	0.005	-10000	0	-10000	0	0
ICAM1	0.027	0.019	-10000	0	-0.44	1	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.037	0.1	-10000	0	-0.3	41	41
cell adhesion	0.012	0.085	-10000	0	-0.35	14	14
NFKB1	0.02	0.13	0.48	4	-0.44	12	16
THY1	0.01	0.087	-10000	0	-0.44	22	22
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	-0.021	0.11	-10000	0	-0.24	118	118
alphaM/beta2 Integrin/LRP/tPA	0.037	0.078	-10000	0	-0.31	11	11
IL6	-0.01	0.16	-10000	0	-0.59	12	12
ITGB2	0.012	0.055	-10000	0	-0.36	10	10
elevation of cytosolic calcium ion concentration	0.02	0.11	-10000	0	-0.28	52	52
alphaM/beta2 Integrin/JAM2/JAM3	-0.008	0.14	-10000	0	-0.38	36	36
JAM2	-0.058	0.16	-10000	0	-0.36	133	133
alphaM/beta2 Integrin/ICAM1	0.006	0.13	-10000	0	-0.33	28	28
alphaM/beta2 Integrin/uPA/Plg	-0.047	0.15	-10000	0	-0.27	164	164
RhoA/GTP	-0.041	0.1	-10000	0	-0.31	38	38
positive regulation of phagocytosis	-0.026	0.094	0.18	2	-0.41	15	17
Ron/MSP	-0.017	0.13	-10000	0	-0.32	99	99
alphaM/beta2 Integrin/uPAR/uPA	0.021	0.11	-10000	0	-0.28	52	52
alphaM/beta2 Integrin/uPAR	0.022	0.083	-10000	0	-0.37	12	12
PLAU	-0.005	0.12	-10000	0	-0.44	42	42
PLAT	0.022	0.03	-10000	0	-0.39	3	3
actin filament polymerization	-0.038	0.096	0.22	3	-0.32	18	21
MST1	-0.048	0.17	-10000	0	-0.44	98	98
alphaM/beta2 Integrin/lipoprotein(a)	-0.017	0.12	-10000	0	-0.27	66	66
TNF	0.012	0.13	0.37	2	-0.66	7	9
RAP1B	0.028	0.003	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.002	0.11	-10000	0	-0.3	54	54
fibrinolysis	-0.048	0.15	-10000	0	-0.27	164	164
HCK	0.011	0.047	-10000	0	-0.36	9	9
dendritic cell antigen processing and presentation	-0.037	0.1	-10000	0	-0.3	41	41
VTN	0.006	0.082	-10000	0	-0.44	19	19
alphaM/beta2 Integrin/CYR61	0.02	0.088	-10000	0	-0.27	36	36
LPA	-0.015	0.099	-10000	0	-0.45	29	29
LRP1	0.026	0.022	-10000	0	-0.36	2	2
cell migration	-0.002	0.097	0.21	12	-0.3	39	51
FN1	0.001	0.11	-10000	0	-0.43	36	36
alphaM/beta2 Integrin/Thy1	0.011	0.1	-10000	0	-0.31	34	34
MPO	0.008	0.084	-10000	0	-0.44	20	20
KNG1	-0.062	0.15	-10000	0	-0.36	128	128
RAP1/GDP	0.036	0.008	-10000	0	-10000	0	0
ROCK1	-0.035	0.097	0.25	2	-0.34	14	16
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.095	0.18	0.36	1	-0.45	127	128
CTGF	0.025	0.033	-10000	0	-0.44	3	3
alphaM/beta2 Integrin/Hck	0.011	0.076	-10000	0	-0.29	22	22
ITGAM	-0.002	0.092	-10000	0	-0.36	34	34
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.016	0.12	-10000	0	-0.38	24	24
HP	-0.007	0.11	-10000	0	-0.44	34	34
leukocyte adhesion	-0.027	0.13	-10000	0	-0.4	31	31
SELP	-0.019	0.12	-10000	0	-0.36	72	72

×

Canonical Wnt 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.011	-10000	0	-10000	0	0
AES	0.027	0.009	-10000	0	-10000	0	0
FBXW11	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.038	0.02	-10000	0	-0.25	2	2
SMAD4	0.02	0.013	-10000	0	-10000	0	0
DKK2	-0.042	0.16	-10000	0	-0.44	89	89
TLE1	0.027	0.017	-10000	0	-0.35	1	1
MACF1	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.044	0.078	0.28	11	-0.31	2	13
WIF1	-0.08	0.18	0.35	1	-0.44	125	126
beta catenin/RanBP3	0.03	0.082	0.29	12	-10000	0	12
KREMEN2	-0.028	0.15	0.36	2	-0.44	73	75
DKK1	-0.075	0.19	0.36	1	-0.44	128	129
beta catenin/beta TrCP1	0.056	0.076	0.3	9	-0.32	1	10
FZD1	0.026	0.023	-10000	0	-0.36	2	2
AXIN2	-0.009	0.12	0.55	10	-10000	0	10
AXIN1	0.027	0.016	-10000	0	-0.36	1	1
RAN	0.028	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.032	0.062	-10000	0	-0.51	5	5
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.026	0.15	0.3	3	-0.5	26	29
Axin1/APC/GSK3	0.055	0.065	0.22	10	-0.28	6	16
Axin1/APC/GSK3/beta catenin/Macf1	0.025	0.07	0.28	2	-0.35	2	4
HNF1A	0.026	0.024	-10000	0	-0.36	2	2
CTBP1	0.027	0.009	-10000	0	-10000	0	0
MYC	0.097	0.21	0.58	91	-10000	0	91
RANBP3	0.027	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.03	0.14	0.23	2	-0.27	154	156
NKD1	-0.28	0.23	0.36	8	-0.44	401	409
TCF4	0.019	0.026	-10000	0	-0.36	2	2
TCF3	0.027	0.009	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.062	0.035	-10000	0	-0.22	6	6
Ran/GTP	0.02	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.013	0.09	0.31	1	-0.42	7	8
LEF1	-0.031	0.16	-10000	0	-0.45	75	75
DVL1	0.027	0.057	0.18	1	-0.37	5	6
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.021	0.1	0.34	2	-0.58	8	10
DKK1/LRP6/Kremen 2	-0.049	0.16	0.25	1	-0.29	183	184
LRP6	0.027	0.005	-10000	0	-10000	0	0
CSNK1A1	0.027	0.01	-10000	0	-10000	0	0
NLK	0.027	0.005	-10000	0	-10000	0	0
CCND1	0.003	0.049	0.55	1	-10000	0	1
WNT1	0.018	0.036	-10000	0	-0.44	3	3
GSK3A	0.028	0.004	-10000	0	-10000	0	0
GSK3B	0.028	0.002	-10000	0	-10000	0	0
FRAT1	0.027	0.005	-10000	0	-10000	0	0
PPP2R5D	0.14	0.1	0.24	138	-0.26	1	139
APC	0.009	0.067	0.22	35	-0.23	3	38
WNT1/LRP6/FZD1	0.041	0.053	0.22	6	-0.2	1	7
CREBBP	0.027	0.009	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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
PTK2	0.006	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.02	0.079	-10000	0	-0.2	66	66
regulation of S phase of mitotic cell cycle	0.003	0.047	-10000	0	-0.2	30	30
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
HRAS	0.027	0.016	-10000	0	-0.36	1	1
SHBG/T-DHT	0.011	0.037	-10000	0	-0.32	7	7
PELP1	0.023	0.01	-10000	0	-10000	0	0
AKT1	0.007	0.002	-10000	0	-10000	0	0
MAP2K1	0.049	0.097	0.17	212	-10000	0	212
T-DHT/AR	-0.002	0.072	-10000	0	-0.25	47	47
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.009	10	10
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.015	0.067	-10000	0	-0.36	19	19
mol:GDP	-0.019	0.078	-10000	0	-0.28	45	45
cell proliferation	0.041	0.11	0.25	10	-0.35	8	18
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
FOS	0.034	0.12	0.26	1	-0.73	10	11
mol:Ca2+	-0.017	0.03	-10000	0	-0.078	68	68
MAPK3	0.046	0.1	0.27	11	-0.28	2	13
MAPK1	0.021	0.1	0.21	1	-0.4	22	23
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	10	10
cAMP biosynthetic process	0.002	0.039	-10000	0	-0.3	7	7
GNG2	0.011	0.074	-10000	0	-0.36	23	23
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	10	10
HRAS/GTP	0.018	0.051	-10000	0	-0.22	1	1
actin cytoskeleton reorganization	0.035	0.021	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	10	10
PI3K	0.035	0.013	-10000	0	-0.21	1	1
apoptosis	-0.042	0.096	0.35	12	-0.22	5	17
T-DHT/AR/PELP1	0.012	0.064	-10000	0	-0.2	47	47
HRAS/GDP	-0.008	0.078	-10000	0	-0.29	39	39
CREB1	0.042	0.1	0.24	3	-0.37	12	15
RAC1-CDC42/GTP	0.044	0.025	-10000	0	-10000	0	0
AR	-0.009	0.1	-10000	0	-0.36	47	47
GNB1	0.026	0.006	-10000	0	-10000	0	0
RAF1	0.063	0.097	0.18	193	-10000	0	193
RAC1-CDC42/GDP	0.033	0.093	-10000	0	-0.31	29	29
T-DHT/AR/PELP1/Src	0.017	0.054	-10000	0	-0.19	30	30
MAP2K2	0.048	0.098	0.17	214	-0.31	1	215
T-DHT/AR/PELP1/Src/PI3K	0.003	0.048	-10000	0	-0.2	30	30
GNAZ	0.023	0.035	-10000	0	-0.36	5	5
SHBG	0.01	0.061	-10000	0	-0.52	7	7
Gi family/GNB1/GNG2/GDP	-0.1	0.19	-10000	0	-0.43	101	101
mol:T-DHT	0	0.001	-10000	0	-0.004	10	10
RAC1	0.025	0.008	-10000	0	-10000	0	0
GNRH1	0.005	0.011	-10000	0	-0.25	1	1
Gi family/GTP	-0.062	0.11	-10000	0	-0.3	67	67
CDC42	0.025	0.017	-10000	0	-0.36	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.024	0.098	-10000	0	-0.35	37	37
HDAC1	0.024	0.006	-10000	0	-10000	0	0
AES	0.027	0.004	-10000	0	-10000	0	0
FBXW11	0.027	0.004	-10000	0	-10000	0	0
DTX1	0.024	0.035	-10000	0	-0.36	5	5
LRP6/FZD1	0.037	0.02	-10000	0	-0.25	2	2
TLE1	0.026	0.016	-10000	0	-0.36	1	1
AP1	-0.083	0.098	0.21	7	-0.29	57	64
NCSTN	0.027	0.004	-10000	0	-10000	0	0
ADAM10	0.026	0.006	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.041	0.081	-10000	0	-0.57	9	9
NICD/RBPSUH	0.023	0.096	-10000	0	-0.35	34	34
WIF1	-0.08	0.18	0.36	1	-0.44	125	126
NOTCH1	0.005	0.096	-10000	0	-0.37	37	37
PSENEN	0.026	0.016	-10000	0	-0.36	1	1
KREMEN2	-0.028	0.15	0.36	2	-0.44	73	75
DKK1	-0.075	0.19	0.36	1	-0.44	128	129
beta catenin/beta TrCP1	0.093	0.075	0.28	10	-0.29	1	11
APH1B	0.026	0.006	-10000	0	-10000	0	0
APH1A	0.027	0.004	-10000	0	-10000	0	0
AXIN1	-0.027	0.065	-10000	0	-0.41	8	8
CtBP/CBP/TCF1/TLE1/AES	0.019	0.025	-10000	0	-0.28	1	1
PSEN1	0.026	0.007	-10000	0	-10000	0	0
FOS	0.022	0.039	-10000	0	-0.36	6	6
JUN	0.027	0.004	-10000	0	-10000	0	0
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.082	0.078	0.27	14	-0.3	1	15
MAPK3	0.027	0.016	-10000	0	-0.36	1	1
DKK2/LRP6/Kremen 2	-0.03	0.14	0.23	2	-0.27	154	156
HNF1A	0.026	0.022	-10000	0	-0.36	2	2
CTBP1	0.026	0.005	-10000	0	-10000	0	0
MYC	0.023	0.042	-10000	0	-10000	0	0
NKD1	-0.28	0.23	0.36	8	-0.44	401	409
FZD1	0.025	0.023	-10000	0	-0.36	2	2
NOTCH1 precursor/Deltex homolog 1	0.022	0.098	-10000	0	-0.35	37	37
apoptosis	-0.082	0.098	0.21	7	-0.29	57	64
Delta 1/NOTCHprecursor	0.022	0.098	-10000	0	-0.35	37	37
DLL1	0.025	0.031	-10000	0	-0.36	4	4
PPARD	0.028	0.075	-10000	0	-0.86	4	4
Gamma Secretase	0.071	0.031	-10000	0	-10000	0	0
APC	-0.05	0.12	-10000	0	-0.42	45	45
DVL1	0.001	0.081	-10000	0	-0.35	24	24
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.049	0.16	0.25	1	-0.29	183	184
LRP6	0.027	0.004	-10000	0	-10000	0	0
CSNK1A1	0.028	0.004	-10000	0	-10000	0	0
NLK	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.018	0.11	-10000	0	-0.8	10	10
WNT1	0.011	0.038	-10000	0	-0.44	3	3
Axin1/APC/beta catenin	0.022	0.12	0.49	2	-0.44	16	18
DKK2	-0.042	0.16	-10000	0	-0.44	89	89
NOTCH1 precursor/DVL1	-0.001	0.14	-10000	0	-0.49	30	30
GSK3B	0.027	0.002	-10000	0	-10000	0	0
FRAT1	0.026	0.005	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.024	0.098	-10000	0	-0.35	37	37
PPP2R5D	0.14	0.1	0.25	72	-0.27	4	76
MAPK1	0.026	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0	0.12	-10000	0	-0.25	122	122
RBPJ	0.027	0.004	-10000	0	-10000	0	0
CREBBP	0.029	0.005	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.02	0.002	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.027	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.015	0.043	-10000	0	-10000	0	0
IRAK/TOLLIP	0.03	0.013	-10000	0	-0.24	1	1
IKBKB	0.024	0.009	-10000	0	-10000	0	0
IKBKG	0.027	0.016	-10000	0	-0.36	1	1
IL1 alpha/IL1R2	-0.12	0.18	-10000	0	-0.3	297	297
IL1A	-0.1	0.21	-10000	0	-0.44	166	166
IL1B	-0.019	0.097	-10000	0	-0.31	61	61
IRAK/TRAF6/p62/Atypical PKCs	0.063	0.028	-10000	0	-10000	0	0
IL1R2	-0.068	0.17	-10000	0	-0.36	151	151
IL1R1	0.023	0.041	-10000	0	-0.36	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.01	0.044	-10000	0	-10000	0	0
TOLLIP	0.027	0.003	-10000	0	-10000	0	0
TICAM2	0.014	0.055	-10000	0	-0.36	12	12
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.022	0.056	-10000	0	-0.35	1	1
JUN	-0.011	0.022	0.2	4	-10000	0	4
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.038	0.091	-10000	0	-0.31	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.018	0.14	-10000	0	-0.25	165	165
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.006	0.14	-10000	0	-0.24	162	162
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.089	-10000	0	-0.24	67	67
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.009	0.023	0.21	4	-10000	0	4
IRAK1	0.014	0.012	-10000	0	-0.27	1	1
IL1RN/IL1R1	0.002	0.11	-10000	0	-0.31	69	69
IRAK4	0.028	0.002	-10000	0	-10000	0	0
PRKCI	0.026	0.022	-10000	0	-0.36	2	2
TRAF6	0.027	0.003	-10000	0	-10000	0	0
PI3K	0.039	0.015	-10000	0	-0.25	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.013	0.048	-10000	0	-0.3	1	1
CHUK	0.027	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.089	-10000	0	-0.24	67	67
IL1 beta/IL1R2	-0.054	0.13	-10000	0	-0.24	201	201
IRAK/TRAF6/TAK1/TAB1/TAB2	0.038	0.014	-10000	0	-0.21	1	1
NF kappa B1 p50/RelA	0.026	0.083	-10000	0	-0.28	1	1
IRAK3	0.02	0.054	-10000	0	-0.36	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.033	0.095	-10000	0	-0.34	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.064	-10000	0	-0.31	3	3
IL1 alpha/IL1R1/IL1RAP	-0.034	0.15	-10000	0	-0.27	170	170
RELA	0.027	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.027	0.004	-10000	0	-10000	0	0
MYD88	0.027	0.003	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.045	0.017	-10000	0	-0.23	1	1
IL1RAP	0.028	0.002	-10000	0	-10000	0	0
UBE2N	0.027	0.003	-10000	0	-10000	0	0
IRAK/TRAF6	0.007	0.078	-10000	0	-0.32	2	2
CASP1	0.025	0.027	-10000	0	-0.36	3	3
IL1RN/IL1R2	-0.067	0.15	-10000	0	-0.27	212	212
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.029	0.09	-10000	0	-0.23	55	55
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.06	-10000	0	-0.31	8	8
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
IL1RN	-0.02	0.14	-10000	0	-0.44	62	62
TRAF6/TAK1/TAB1/TAB2	0.039	0.008	-10000	0	-10000	0	0
MAP2K6	0.013	0.023	0.22	4	-10000	0	4

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.022	0.011	-10000	0	-10000	0	0
EPHB2	0.024	0.034	-10000	0	-0.44	3	3
EFNB1	0.007	0.035	0.27	2	-0.31	5	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.015	0.13	-10000	0	-0.36	16	16
Ephrin B2/EPHB1-2	-0.006	0.1	0.26	1	-0.24	89	90
neuron projection morphogenesis	-0.026	0.11	-10000	0	-0.34	18	18
Ephrin B1/EPHB1-2/Tiam1	-0.027	0.13	-10000	0	-0.26	106	106
DNM1	0.025	0.046	0.35	2	-0.44	5	7
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.007	0.066	0.24	1	-0.41	14	15
YES1	-0.008	0.11	-10000	0	-0.65	15	15
Ephrin B1/EPHB1-2/NCK2	-0.004	0.12	0.28	1	-0.23	113	114
PI3K	0.031	0.082	-10000	0	-0.39	18	18
mol:GDP	-0.028	0.13	-10000	0	-0.25	107	107
ITGA2B	0.006	0.089	-10000	0	-0.44	23	23
endothelial cell proliferation	0.028	0.016	-10000	0	-10000	0	0
FYN	-0.006	0.11	-10000	0	-0.64	16	16
MAP3K7	-0.011	0.071	-10000	0	-0.44	15	15
FGR	-0.009	0.11	-10000	0	-0.63	18	18
TIAM1	-0.011	0.11	-10000	0	-0.36	59	59
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
RGS3	0.027	0.004	-10000	0	-10000	0	0
cell adhesion	0.01	0.09	-10000	0	-0.4	16	16
LYN	-0.006	0.11	-10000	0	-0.63	17	17
Ephrin B1/EPHB1-2/Src Family Kinases	-0.009	0.092	-10000	0	-0.54	17	17
Ephrin B1/EPHB1-2	-0.009	0.074	-10000	0	-0.49	13	13
SRC	-0.007	0.1	-10000	0	-0.61	16	16
ITGB3	0.023	0.041	-10000	0	-0.36	7	7
EPHB1	-0.07	0.19	0.35	1	-0.44	129	130
EPHB4	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.029	0.016	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.023	0.074	-10000	0	-0.3	30	30
BLK	-0.043	0.12	-10000	0	-0.66	15	15
HCK	-0.01	0.1	-10000	0	-0.63	15	15
regulation of stress fiber formation	0.005	0.12	0.23	113	-0.27	1	114
MAPK8	-0.006	0.067	0.22	1	-0.39	14	15
Ephrin B1/EPHB1-2/RGS3	-0.005	0.12	0.28	1	-0.24	95	96
endothelial cell migration	0.018	0.091	0.23	60	-0.36	9	69
NCK2	0.028	0.001	-10000	0	-10000	0	0
PTPN13	0.005	0.088	-10000	0	-0.4	27	27
regulation of focal adhesion formation	0.005	0.12	0.23	113	-0.27	1	114
chemotaxis	0.006	0.12	0.24	95	-0.27	1	96
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
Rac1/GTP	-0.02	0.12	-10000	0	-0.35	17	17
angiogenesis	-0.01	0.075	-10000	0	-0.49	14	14
LCK	-0.009	0.11	-10000	0	-0.62	18	18

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.027	0.036	0.36	3	-0.44	2	5
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.027	0.003	-10000	0	-10000	0	0
CDKN1A	0.007	0.048	-10000	0	-0.31	13	13
PRL-3/alpha Tubulin	0.021	0.12	0.26	42	-0.32	53	95
mol:Ca2+	-0.062	0.13	0.18	35	-0.3	118	153
AGT	-0.035	0.16	0.36	2	-0.44	82	84
CCNA2	-0.003	0.01	-10000	0	-10000	0	0
TUBA1B	0.028	0.002	-10000	0	-10000	0	0
EGR1	0.014	0.015	-10000	0	-0.24	2	2
CDK2/Cyclin E1	0.074	0.077	0.33	2	-0.34	1	3
MAPK3	0.001	0.12	0.28	42	-0.32	54	96
PRL-2 /Rab GGTase beta	0.039	0.009	-10000	0	-10000	0	0
MAPK1	0.001	0.12	0.28	41	-0.32	53	94
PTP4A1	0.002	0.011	-10000	0	-10000	0	0
PTP4A3	0.007	0.16	0.36	42	-0.44	53	95
PTP4A2	0.027	0.005	-10000	0	-10000	0	0
ITGB1	0.002	0.12	0.28	42	-0.32	53	95
SRC	0.017	0.014	-10000	0	-10000	0	0
RAC1	0.024	0.069	0.3	25	-0.3	4	29
Rab GGTase beta/Rab GGTase alpha	0.037	0.012	-10000	0	-10000	0	0
PRL-1/ATF-5	0.085	0.083	-10000	0	-10000	0	0
RABGGTA	0.026	0.007	-10000	0	-10000	0	0
BCAR1	-0.019	0.081	0.16	53	-0.25	42	95
RHOC	0.023	0.082	0.3	28	-0.32	11	39
RHOA	0.024	0.076	0.3	27	-0.3	8	35
cell motility	0.048	0.11	0.32	25	-0.36	6	31
PRL-1/alpha Tubulin	0.086	0.083	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.02	0.12	0.26	40	-0.32	53	93
ROCK1	0.05	0.1	0.32	25	-0.37	5	30
RABGGTB	0.027	0.005	-10000	0	-10000	0	0
CDK2	0.028	0.002	-10000	0	-10000	0	0
mitosis	0.002	0.011	-10000	0	-10000	0	0
ATF5	0.027	0.004	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0.069	0.6	4	-10000	0	4
VDR	0.028	0.002	-10000	0	-10000	0	0
FAM120B	0.027	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.051	0.11	-10000	0	-0.35	6	6
RXRs/LXRs/DNA/Oxysterols	-0.037	0.11	-10000	0	-0.4	10	10
MED1	0.028	0.019	0.36	2	-10000	0	2
mol:9cRA	0.003	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.033	0.1	0.17	1	-0.32	7	8
RXRs/NUR77	-0.041	0.13	-10000	0	-0.32	12	12
RXRs/PPAR	-0.061	0.11	-10000	0	-0.28	29	29
NCOR2	0.027	0.016	-10000	0	-0.36	1	1
VDR/VDR/Vit D3	0.02	0.002	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.061	0.028	0.24	1	-0.18	5	6
RARA	0.027	0.021	0.36	1	-0.36	1	2
NCOA1	0.028	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.028	0.002	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.046	0.026	0.22	1	-0.18	5	6
RARG	0.028	0.002	-10000	0	-10000	0	0
RPS6KB1	0.032	0.077	0.59	10	-0.34	1	11
RARs/THRs/DNA/SMRT	-0.033	0.1	0.17	1	-0.34	7	8
THRA	0.027	0.014	0.36	1	-10000	0	1
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.02	0.002	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.042	0.12	-10000	0	-0.29	2	2
NR1H4	-0.18	0.19	-10000	0	-0.36	308	308
RXRs/LXRs/DNA	-0.02	0.13	-10000	0	-0.34	3	3
NR1H2	0.029	0.019	-10000	0	-0.36	1	1
NR1H3	0.03	0.012	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.035	0.12	-10000	0	-0.24	2	2
NR4A1	0.02	0.059	-10000	0	-0.43	10	10
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.15	0.14	-10000	0	-0.3	215	215
RXRG	-0.13	0.19	-10000	0	-0.36	253	253
RXR alpha/CCPG	0.041	0.017	-10000	0	-0.25	1	1
RXRA	0.029	0.019	-10000	0	-0.36	1	1
RXRB	0.03	0.012	-10000	0	-10000	0	0
THRB	-0.086	0.18	-10000	0	-0.36	178	178
PPARG	0.026	0.022	-10000	0	-0.36	2	2
PPARD	0.027	0.016	-10000	0	-0.36	1	1
TNF	-0.041	0.12	-10000	0	-0.85	6	6
mol:Oxysterols	0.003	0.006	-10000	0	-10000	0	0
cholesterol transport	-0.037	0.1	-10000	0	-0.4	10	10
PPARA	0.026	0.006	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.025	0.031	-10000	0	-0.36	4	4
RXRs/NUR77/BCL2	-0.085	0.12	-10000	0	-0.22	257	257
SREBF1	-0.029	0.09	-10000	0	-0.49	2	2
RXRs/RXRs/DNA/9cRA	-0.042	0.12	-10000	0	-0.29	2	2
ABCA1	-0.042	0.13	-10000	0	-0.89	7	7
RARs/THRs	0.003	0.12	0.26	1	-0.35	2	3
RXRs/FXR	-0.15	0.16	-10000	0	-0.36	141	141
BCL2	0.014	0.05	-10000	0	-0.36	10	10

×

TCGA08_p53

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
CDKN2A	-0.054	0.13	0.26	2	-0.32	115	117
TP53	-0.017	0.062	-10000	0	-0.28	27	27
Senescence	-0.017	0.062	-10000	0	-0.27	27	27
Apoptosis	-0.017	0.062	-10000	0	-0.27	27	27
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.022	0.068	0.31	7	-0.18	2	9
MDM4	0.028	0.014	0.36	1	-10000	0	1

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.036	-10000	0	-0.22	3	3
NFATC2	-0.015	0.044	-10000	0	-0.23	16	16
NFATC3	-0.014	0.037	-10000	0	-10000	0	0
CD40LG	-0.058	0.2	0.37	2	-0.56	29	31
PTGS2	-0.057	0.2	0.36	1	-0.57	34	35
JUNB	0.026	0.022	-10000	0	-0.36	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.029	-10000	0	-10000	0	0
CaM/Ca2+	-0.005	0.029	-10000	0	-10000	0	0
CALM1	0.009	0.026	-10000	0	-10000	0	0
JUN	0.009	0.027	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.012	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.013	-10000	0	-10000	0	0
FOSL1	-0.27	0.23	0.36	1	-0.44	385	386
CREM	0.028	0.002	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.013	0.13	-10000	0	-0.41	9	9
FOS	0.005	0.045	-10000	0	-0.36	6	6
IFNG	-0.066	0.21	0.36	1	-0.55	46	47
AP-1/NFAT1-c-4	-0.055	0.21	-10000	0	-0.48	55	55
FASLG	-0.055	0.2	0.36	1	-0.55	22	23
NFAT1-c-4/ICER1	-0.018	0.077	-10000	0	-0.34	2	2
IL2RA	-0.051	0.19	0.37	2	-0.58	16	18
FKBP12/FK506	0.017	0.008	-10000	0	-10000	0	0
CSF2	-0.12	0.25	0.37	2	-0.54	75	77
JunB/Fra1/NFAT1-c-4	-0.097	0.16	-10000	0	-0.32	138	138
IL4	-0.053	0.18	0.36	2	-0.56	13	15
IL2	-0.016	0.14	-10000	0	-0.84	18	18
IL3	0	0.086	-10000	0	-0.6	11	11
FKBP1A	0.023	0.011	-10000	0	-10000	0	0
BATF3	0.022	0.049	-10000	0	-0.43	7	7
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.026	0.02	-10000	0	-0.44	1	1

×

Thromboxane A2 receptor signaling

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
TGM2	0.013	0.039	-10000	0	-0.44	4	4
GNB1/GNG2	-0.052	0.049	-10000	0	-0.18	28	28
AKT1	-0.041	0.093	0.29	4	-0.28	39	43
EGF	-0.06	0.16	-10000	0	-0.37	127	127
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.069	0.077	0.39	1	-0.28	2	3
mol:Ca2+	-0.053	0.097	0.29	4	-0.28	43	47
LYN	-0.06	0.075	0.39	1	-10000	0	1
RhoA/GTP	-0.024	0.043	-10000	0	-0.14	9	9
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.059	0.1	0.3	5	-0.32	23	28
GNG2	0.011	0.074	-10000	0	-0.36	23	23
ARRB2	0.023	0.01	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.027	0.11	-10000	0	-0.59	15	15
G beta5/gamma2	-0.06	0.066	-10000	0	-0.23	28	28
PRKCH	-0.056	0.1	0.28	4	-0.32	28	32
DNM1	0.025	0.046	0.36	2	-0.44	5	7
TXA2/TP beta/beta Arrestin3	-0.01	0.049	-10000	0	-0.62	3	3
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.18	0.19	-10000	0	-0.36	317	317
G12 family/GTP	-0.055	0.087	-10000	0	-0.29	24	24
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
ADRBK2	0.027	0.005	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.03	0.018	-10000	0	-0.21	1	1
mol:GDP	0.067	0.098	0.31	39	-0.29	2	41
mol:NADP	0.02	0.058	0.36	1	-0.44	9	10
RAB11A	0.027	0.006	-10000	0	-10000	0	0
PRKG1	0.013	0.071	-10000	0	-0.36	21	21
mol:IP3	-0.066	0.12	0.31	4	-0.35	43	47
cell morphogenesis	0.029	0.017	-10000	0	-0.21	1	1
PLCB2	-0.089	0.15	0.46	1	-0.47	43	44
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.099	0.11	-10000	0	-0.28	101	101
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.041	0.069	-10000	0	-0.28	5	5
RHOA	0.027	0.004	-10000	0	-10000	0	0
PTGIR	0.026	0.027	-10000	0	-0.44	2	2
PRKCB1	-0.06	0.11	0.29	4	-0.33	35	39
GNAQ	0.026	0.022	-10000	0	-0.36	2	2
mol:L-citrulline	0.02	0.058	0.36	1	-0.44	9	10
TXA2/TXA2-R family	-0.085	0.14	0.38	2	-0.48	25	27
LCK	-0.072	0.079	0.39	1	-0.3	6	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.078	0.097	-10000	0	-0.23	4	4
TXA2-R family/G12 family/GDP/G beta/gamma	-0.029	0.11	-10000	0	-0.48	31	31
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.071	0.096	-10000	0	-0.23	2	2
MAPK14	-0.041	0.075	0.3	5	-0.23	16	21
TGM2/GTP	-0.076	0.12	0.3	3	-0.4	32	35
MAPK11	-0.041	0.073	0.24	5	-0.23	18	23
ARHGEF1	-0.034	0.057	0.25	1	-0.18	16	17
GNAI2	0.027	0.004	-10000	0	-10000	0	0
JNK cascade	-0.066	0.11	0.31	4	-0.36	25	29
RAB11/GDP	0.027	0.006	-10000	0	-10000	0	0
ICAM1	-0.044	0.084	0.26	4	-0.28	17	21
cAMP biosynthetic process	-0.069	0.11	0.31	4	-0.34	42	46
Gq family/GTP/EBP50	0.016	0.045	0.24	5	-0.29	7	12
actin cytoskeleton reorganization	0.029	0.017	-10000	0	-0.21	1	1
SRC	-0.039	0.066	-10000	0	-10000	0	0
GNB5	0.026	0.006	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.061	0.099	0.21	7	-0.27	36	43
VCAM1	-0.049	0.092	0.27	4	-0.35	17	21
TP beta/Gq family/GDP/G beta5/gamma2	-0.027	0.11	-10000	0	-0.59	15	15
platelet activation	-0.054	0.098	0.35	5	-0.3	22	27
PGI2/IP	0.019	0.019	-10000	0	-0.31	2	2
PRKACA	-0.09	0.1	-10000	0	-0.19	309	309
Gq family/GDP/G beta5/gamma2	-0.033	0.1	-10000	0	-0.5	16	16
TXA2/TP beta/beta Arrestin2	-0.026	0.061	-10000	0	-0.37	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.091	0.094	-10000	0	-0.18	303	303
mol:DAG	-0.067	0.12	0.31	4	-0.37	36	40
EGFR	0.024	0.023	-10000	0	-0.36	2	2
TXA2/TP alpha	-0.089	0.15	0.35	4	-0.45	42	46
Gq family/GTP	0.01	0.055	0.31	5	-0.24	16	21
YES1	-0.06	0.076	0.39	1	-10000	0	1
GNAI2/GTP	-0.071	0.089	-10000	0	-0.23	2	2
PGD2/DP	-0.12	0.13	-10000	0	-0.25	317	317
SLC9A3R1	0.027	0.004	-10000	0	-10000	0	0
FYN	-0.07	0.076	0.39	1	-10000	0	1
mol:NO	0.02	0.058	0.36	1	-0.44	9	10
GNA15	0.023	0.046	-10000	0	-0.44	6	6
PGK/cGMP	0.022	0.058	0.23	1	-0.23	28	29
RhoA/GDP	0.028	0.005	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.037	0.096	-10000	0	-0.31	12	12
NOS3	0.02	0.058	0.36	1	-0.44	9	10
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.056	0.1	0.31	4	-0.32	28	32
PRKCB	-0.077	0.12	0.34	3	-0.38	33	36
PRKCE	-0.054	0.1	0.32	2	-0.32	24	26
PRKCD	-0.058	0.11	0.28	4	-0.35	22	26
PRKCG	-0.086	0.13	0.32	4	-0.36	42	46
muscle contraction	-0.083	0.14	0.35	4	-0.44	31	35
PRKCZ	-0.06	0.1	0.29	4	-0.33	21	25
ARR3	-0.008	0.037	-10000	0	-0.44	3	3
TXA2/TP beta	-0.072	0.1	-10000	0	-0.23	3	3
PRKCQ	-0.055	0.1	0.32	4	-0.32	25	29
MAPKKK cascade	-0.078	0.13	0.32	4	-0.41	40	44
SELE	-0.058	0.099	0.27	4	-0.26	36	40
TP beta/GNAI2/GDP/G beta/gamma	-0.072	0.11	-10000	0	-0.3	17	17
ROCK1	0.022	0.019	-10000	0	-0.36	1	1
GNA14	0.024	0.035	-10000	0	-0.36	5	5
chemotaxis	-0.087	0.15	0.47	1	-0.57	18	19
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.031	-10000	0	-0.36	4	4
Rac1/GTP	0.018	0.006	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.02	0.1	-10000	0	-0.21	133	133
cell-cell adhesion	0.04	0.068	0.36	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	0.049	0.05	-10000	0	-0.23	4	4
ITSN1	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.018	0.073	-10000	0	-0.27	38	38
Ephrin B1/EPHB1	-0.027	0.12	0.23	1	-0.27	129	130
HRAS/GDP	-0.023	0.1	-10000	0	-0.31	19	19
Ephrin B/EPHB1/GRB7	0.012	0.11	0.26	6	-0.24	65	71
Endophilin/SYNJ1	0.029	0.079	0.18	122	-10000	0	122
KRAS	0.026	0.016	-10000	0	-0.36	1	1
Ephrin B/EPHB1/Src	0.01	0.085	-10000	0	-0.24	43	43
endothelial cell migration	0.043	0.028	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.035	0.049	0.36	14	-10000	0	14
PAK1	0.03	0.085	0.26	9	-10000	0	9
HRAS	0.027	0.016	-10000	0	-0.36	1	1
RRAS	0.031	0.081	0.18	124	-10000	0	124
DNM1	0.025	0.046	0.36	2	-0.44	5	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.019	0.1	0.18	73	-0.42	1	74
lamellipodium assembly	-0.04	0.068	-10000	0	-0.36	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.015	0.06	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
EPHB2	0.024	0.033	-10000	0	-0.44	3	3
EPHB3	-0.002	0.11	-10000	0	-0.44	38	38
EPHB1	-0.071	0.19	0.36	1	-0.44	129	130
EPHB4	0.027	0.006	-10000	0	-10000	0	0
mol:GDP	-0.012	0.09	0.27	3	-0.3	18	21
Ephrin B/EPHB2	0.039	0.043	-10000	0	-0.23	5	5
Ephrin B/EPHB3	0.026	0.073	-10000	0	-0.23	36	36
JNK cascade	-0.038	0.1	0.35	4	-0.4	3	7
Ephrin B/EPHB1	-0.001	0.1	-10000	0	-0.23	88	88
RAP1/GDP	0.003	0.11	0.31	16	-0.28	16	32
EFNB2	0.022	0.011	-10000	0	-10000	0	0
EFNB3	0.018	0.045	-10000	0	-0.38	7	7
EFNB1	0.028	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.007	0.1	0.24	1	-0.24	89	90
RAP1B	0.028	0.003	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.007	0.096	-10000	0	-0.36	3	3
Rap1/GTP	-0.016	0.082	-10000	0	-0.37	3	3
axon guidance	-0.02	0.1	-10000	0	-0.21	133	133
MAPK3	0.007	0.054	0.21	2	-10000	0	2
MAPK1	0.008	0.051	0.17	1	-10000	0	1
Rac1/GDP	-0.013	0.097	0.24	4	-0.29	15	19
actin cytoskeleton reorganization	-0.034	0.076	-10000	0	-0.31	4	4
CDC42/GDP	-0.003	0.11	0.31	17	-0.28	17	34
PI3K	0.048	0.031	-10000	0	-10000	0	0
EFNA5	-0.056	0.16	-10000	0	-0.36	130	130
Ephrin B2/EPHB4	0.029	0.016	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.017	0.026	-10000	0	-10000	0	0
CDC42	0.025	0.017	-10000	0	-0.36	1	1
RAS family/GTP	-0.02	0.082	-10000	0	-0.35	5	5
PTK2	0.087	0.21	0.58	89	-10000	0	89
MAP4K4	-0.038	0.11	0.35	4	-0.4	3	7
SRC	0.017	0.014	-10000	0	-10000	0	0
KALRN	0.027	0.016	-10000	0	-0.36	1	1
Intersectin/N-WASP	0.038	0.011	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.007	0.092	0.3	15	-0.31	1	16
MAP2K1	0.01	0.055	-10000	0	-10000	0	0
WASL	0.027	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.001	0.13	-10000	0	-0.25	129	129
cell migration	0.033	0.088	0.22	50	-10000	0	50
NRAS	0.026	0.023	-10000	0	-0.36	2	2
SYNJ1	0.029	0.08	0.18	122	-10000	0	122
PXN	0.028	0.002	-10000	0	-10000	0	0
TF	0.004	0.098	0.19	27	-0.41	1	28
HRAS/GTP	-0.004	0.094	-10000	0	-0.38	3	3
Ephrin B1/EPHB1-2	-0.013	0.12	0.24	1	-0.25	130	131
cell adhesion mediated by integrin	-0.034	0.091	0.24	3	-0.2	123	126
RAC1	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.003	0.097	-10000	0	-0.4	3	3
RAC1-CDC42/GTP	-0.034	0.095	-10000	0	-0.39	14	14
RASA1	0.027	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.005	0.099	0.26	3	-0.28	14	17
ruffle organization	-0.003	0.13	0.39	29	-0.37	3	32
NCK1	0.028	0.002	-10000	0	-10000	0	0
receptor internalization	0.026	0.079	0.2	28	-10000	0	28
Ephrin B/EPHB2/KALRN	0.049	0.051	-10000	0	-0.23	4	4
ROCK1	-0.003	0.061	0.18	1	-0.23	38	39
RAS family/GDP	-0.043	0.062	-10000	0	-0.31	3	3
Rac1/GTP	-0.021	0.081	-10000	0	-0.38	3	3
Ephrin B/EPHB1/Src/Paxillin	0.001	0.048	-10000	0	-0.21	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.027	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.029	0.093	-10000	0	-0.29	34	34
NT3 (dimer)/TRKC	-0.023	0.12	-10000	0	-0.26	124	124
NT3 (dimer)/TRKB	-0.079	0.17	-10000	0	-0.27	248	248
SHC/Grb2/SOS1/GAB1/PI3K	0.028	0.016	-10000	0	-0.27	1	1
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1
BDNF	0.019	0.06	-10000	0	-0.44	10	10
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
NTRK1	0.016	0.057	-10000	0	-0.43	9	9
NTRK2	-0.087	0.18	-10000	0	-0.37	177	177
NTRK3	-0.058	0.15	-10000	0	-0.36	123	123
NT-4/5 (dimer)/TRKB	-0.092	0.17	-10000	0	-0.27	267	267
neuron apoptosis	0.088	0.16	0.38	88	-10000	0	88
SHC 2-3/Grb2	-0.095	0.17	-10000	0	-0.41	88	88
SHC1	0.027	0.004	-10000	0	-10000	0	0
SHC2	-0.093	0.16	-10000	0	-0.42	93	93
SHC3	-0.097	0.16	-10000	0	-0.42	89	89
STAT3 (dimer)	0.031	0.024	-10000	0	-0.35	1	1
NT3 (dimer)/TRKA	-0.016	0.12	-10000	0	-0.22	151	151
RIN/GDP	-0.005	0.08	0.26	8	-0.24	9	17
GIPC1	0.027	0.016	-10000	0	-0.36	1	1
KRAS	0.026	0.016	-10000	0	-0.36	1	1
DNAJA3	-0.061	0.12	-10000	0	-0.27	135	135
RIN/GTP	0.009	0.014	-10000	0	-0.31	1	1
CCND1	0.017	0.03	-10000	0	-0.35	4	4
MAGED1	0.027	0.003	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.017	0.088	-10000	0	-0.45	23	23
SHC/GRB2/SOS1	0.054	0.012	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.009	0.1	-10000	0	-0.23	91	91
TRKA/NEDD4-2	0.024	0.045	-10000	0	-0.3	10	10
ELMO1	0.023	0.028	-10000	0	-0.36	3	3
RhoG/GTP/ELMO1/DOCK1	0.032	0.023	-10000	0	-0.21	4	4
NGF	0.011	0.071	-10000	0	-0.37	20	20
HRAS	0.027	0.016	-10000	0	-0.36	1	1
DOCK1	0.026	0.016	-10000	0	-0.36	1	1
GAB2	0.027	0.004	-10000	0	-10000	0	0
RIT2	-0.012	0.021	-10000	0	-0.44	1	1
RIT1	0.027	0.004	-10000	0	-10000	0	0
FRS2	0.027	0.003	-10000	0	-10000	0	0
DNM1	0.025	0.046	0.36	2	-0.44	5	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.01	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.046	0.12	-10000	0	-0.26	130	130
mol:GDP	-0.012	0.11	0.29	12	-0.34	13	25
NGF (dimer)	0.011	0.071	-10000	0	-0.37	20	20
RhoG/GDP	0.017	0.02	-10000	0	-0.25	3	3
RIT1/GDP	-0.002	0.083	0.19	10	-0.24	9	19
TIAM1	-0.011	0.11	-10000	0	-0.36	59	59
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.03	0.13	-10000	0	-0.22	170	170
KIDINS220/CRKL/C3G	0.038	0.015	-10000	0	-0.25	1	1
SHC/RasGAP	0.039	0.009	-10000	0	-10000	0	0
FRS2 family/SHP2	0.055	0.012	0.24	1	-10000	0	1
SHC/GRB2/SOS1/GAB1	0.067	0.018	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.003	-10000	0	-10000	0	0
NT3 (dimer)	0.021	0.043	-10000	0	-0.37	7	7
RAP1/GDP	-0.005	0.069	0.13	3	-0.2	9	12
KIDINS220/CRKL	0.026	0.006	-10000	0	-10000	0	0
BDNF (dimer)	0.019	0.06	-10000	0	-0.44	10	10
ubiquitin-dependent protein catabolic process	0.026	0.064	-10000	0	-0.23	29	29
Schwann cell development	-0.026	0.027	-10000	0	-10000	0	0
EHD4	0.026	0.007	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.068	0.018	0.25	1	-10000	0	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.016	0.042	0.25	1	-0.24	2	3
RAP1B	0.028	0.003	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.051	0.12	-10000	0	-0.33	35	35
ABL1	0.027	0.004	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
Rap1/GTP	-0.013	0.095	-10000	0	-0.42	17	17
STAT3	0.031	0.024	-10000	0	-0.35	1	1
axon guidance	-0.054	0.11	-10000	0	-0.32	35	35
MAPK3	-0.02	0.083	0.18	8	-0.31	10	18
MAPK1	-0.019	0.082	0.18	6	-0.31	10	16
CDC42/GDP	0.001	0.088	0.22	16	-0.24	10	26
NTF3	0.021	0.043	-10000	0	-0.37	7	7
NTF4	-0.017	0.089	-10000	0	-0.45	23	23
NGF (dimer)/TRKA/FAIM	0.039	0.064	0.25	1	-0.24	28	29
PI3K	0.039	0.015	-10000	0	-0.25	1	1
FRS3	0.028	0.014	0.36	1	-10000	0	1
FAIM	0.028	0.014	0.36	1	-10000	0	1
GAB1	0.027	0.005	-10000	0	-10000	0	0
RASGRF1	-0.077	0.13	-10000	0	-0.28	146	146
SOS1	0.028	0.002	-10000	0	-10000	0	0
MCF2L	-0.031	0.085	-10000	0	-0.22	101	101
RGS19	0.017	0.014	-10000	0	-10000	0	0
CDC42	0.025	0.017	-10000	0	-0.36	1	1
RAS family/GTP	0.007	0.078	0.47	1	-0.39	6	7
Rac1/GDP	-0.004	0.082	0.22	11	-0.24	10	21
NGF (dimer)/TRKA/GRIT	0.022	0.058	-10000	0	-0.24	28	28
neuron projection morphogenesis	-0.046	0.14	-10000	0	-0.89	3	3
NGF (dimer)/TRKA/NEDD4-2	0.026	0.064	-10000	0	-0.23	29	29
MAP2K1	0.017	0.029	-10000	0	-10000	0	0
NGFR	-0.067	0.17	-10000	0	-0.36	149	149
NGF (dimer)/TRKA/GIPC/GAIP	0.011	0.038	0.17	1	-10000	0	1
RAS family/GTP/PI3K	0.022	0.026	-10000	0	-0.26	4	4
FRS2 family/SHP2/GRB2/SOS1	0.079	0.02	0.25	1	-10000	0	1
NRAS	0.026	0.023	-10000	0	-0.36	2	2
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
PRKCI	0.026	0.022	-10000	0	-0.36	2	2
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.042	0.14	-10000	0	-0.57	37	37
RASA1	0.027	0.005	-10000	0	-10000	0	0
TRKA/c-Abl	0.034	0.043	-10000	0	-0.31	9	9
SQSTM1	0.027	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.013	0.12	-10000	0	-0.27	18	18
NGF (dimer)/TRKA/p62/Atypical PKCs	0.059	0.067	-10000	0	-0.28	8	8
MATK	-0.02	0.13	-10000	0	-0.36	74	74
NEDD4L	0.02	0.02	-10000	0	-0.36	1	1
RAS family/GDP	-0.027	0.044	-10000	0	-0.22	1	1
NGF (dimer)/TRKA	-0.058	0.13	-10000	0	-0.28	139	139
Rac1/GTP	-0.064	0.1	-10000	0	-0.27	58	58
FRS2 family/SHP2/CRK family	0.067	0.034	0.25	1	-10000	0	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.015	0.16	-10000	0	-0.79	18	18
MKNK1	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.01	0.089	-10000	0	-0.3	33	33
ATF2/c-Jun	0.004	0.069	-10000	0	-0.36	4	4
MAPK11	0.01	0.089	-10000	0	-0.31	34	34
MITF	-0.005	0.11	-10000	0	-0.37	39	39
MAPKAPK5	0.002	0.096	-10000	0	-0.34	37	37
KRT8	0.002	0.096	-10000	0	-0.34	37	37
MAPKAPK3	0.027	0.004	-10000	0	-10000	0	0
MAPKAPK2	0.027	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.011	0.13	-10000	0	-0.44	35	35
CEBPB	-0.002	0.082	0.26	3	-0.35	23	26
SLC9A1	-0.001	0.1	-10000	0	-0.36	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.003	0.097	-10000	0	-0.34	35	35
p38alpha-beta/MNK1	0.028	0.11	-10000	0	-0.36	34	34
JUN	0.002	0.067	-10000	0	-0.35	4	4
PPARGC1A	-0.035	0.14	-10000	0	-0.4	44	44
USF1	0.004	0.092	-10000	0	-0.34	34	34
RAB5/GDP/GDI1	0.008	0.077	-10000	0	-0.25	32	32
NOS2	-0.028	0.21	-10000	0	-0.91	28	28
DDIT3	0.002	0.097	-10000	0	-0.35	37	37
RAB5A	0.026	0.022	-10000	0	-0.36	2	2
HSPB1	0.004	0.091	0.28	18	-0.29	30	48
p38alpha-beta/HBP1	0.028	0.11	-10000	0	-0.36	31	31
CREB1	0.002	0.1	-10000	0	-0.38	36	36
RAB5/GDP	0.019	0.016	-10000	0	-0.25	2	2
EIF4E	-0.004	0.089	-10000	0	-0.32	34	34
RPS6KA4	0.002	0.095	-10000	0	-0.34	36	36
PLA2G4A	-0.027	0.11	-10000	0	-0.35	33	33
GDI1	0.003	0.093	-10000	0	-0.34	35	35
TP53	-0.013	0.11	-10000	0	-0.43	32	32
RPS6KA5	-0.001	0.1	-10000	0	-0.37	36	36
ESR1	-0.021	0.13	-10000	0	-0.42	38	38
HBP1	0.027	0.005	-10000	0	-10000	0	0
MEF2C	-0.005	0.11	-10000	0	-0.37	37	37
MEF2A	0.001	0.1	-10000	0	-0.36	37	37
EIF4EBP1	-0.001	0.1	-10000	0	-0.39	34	34
KRT19	0.003	0.093	-10000	0	-0.34	34	34
ELK4	0.003	0.093	-10000	0	-0.34	35	35
ATF6	0.004	0.092	-10000	0	-0.34	34	34
ATF1	0.002	0.1	-10000	0	-0.38	36	36
p38alpha-beta/MAPKAPK2	0.029	0.11	-10000	0	-0.35	32	32
p38alpha-beta/MAPKAPK3	0.028	0.11	-10000	0	-0.36	34	34

×

Arf6 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
CENTA1/KIF3B	0.026	0.024	-10000	0	-0.39	1	1
ARNO/beta Arrestin1-2	0.006	0.092	-10000	0	-0.83	3	3
EGFR	0.024	0.023	-10000	0	-0.36	2	2
EPHA2	0.025	0.027	-10000	0	-0.44	2	2
USP6	0.022	0.026	-10000	0	-0.4	2	2
IQSEC1	0.027	0.004	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.021	0.12	-10000	0	-0.26	115	115
ARRB2	0.008	0.004	-10000	0	-10000	0	0
mol:GTP	0.004	0.04	0.13	9	-0.17	6	15
ARRB1	0.027	0.016	-10000	0	-0.36	1	1
FBXO8	0.026	0.017	-10000	0	-0.36	1	1
TSHR	0.013	0.033	-10000	0	-0.44	2	2
EGF	-0.059	0.16	-10000	0	-0.37	127	127
somatostatin receptor activity	0	0	0.001	33	-0.001	34	67
ARAP2	0.026	0.023	-10000	0	-0.36	2	2
mol:GDP	-0.034	0.11	0.19	13	-0.27	51	64
mol:PI-3-4-5-P3	0	0	0.001	13	-0.001	7	20
ITGA2B	0.006	0.089	-10000	0	-0.44	23	23
ARF6	0.026	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.062	0.03	-10000	0	-0.25	2	2
ADAP1	0.025	0.017	-10000	0	-0.36	1	1
KIF13B	0.021	0.019	-10000	0	-0.36	1	1
HGF/MET	0.029	0.058	-10000	0	-0.28	19	19
PXN	0.028	0.002	-10000	0	-10000	0	0
ARF6/GTP	-0.022	0.11	0.22	30	-0.26	36	66
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.003	0.11	-10000	0	-0.22	115	115
ADRB2	-0.032	0.14	-10000	0	-0.36	93	93
receptor agonist activity	0	0	0	15	0	32	47
actin filament binding	0	0	0	33	-0.001	36	69
SRC	0.017	0.014	-10000	0	-10000	0	0
ITGB3	0.023	0.041	-10000	0	-0.36	7	7
GNAQ	0.026	0.022	-10000	0	-0.36	2	2
EFA6/PI-4-5-P2	0	0.001	0.001	37	-0.001	18	55
ARF6/GDP	-0.047	0.16	0.2	5	-0.42	76	81
ARF6/GDP/GULP/ACAP1	-0.022	0.12	0.22	4	-0.37	21	25
alphaIIb/beta3 Integrin/paxillin/GIT1	0.054	0.066	-10000	0	-0.24	29	29
ACAP1	0.013	0.06	-10000	0	-0.36	15	15
ACAP2	0.027	0.016	-10000	0	-0.36	1	1
LHCGR/beta Arrestin2	0.007	0.026	-10000	0	-10000	0	0
EFNA1	0.027	0.004	-10000	0	-10000	0	0
HGF	0.017	0.061	-10000	0	-0.37	15	15
CYTH3	0.006	0.002	-10000	0	-10000	0	0
CYTH2	0.015	0.071	-10000	0	-1	3	3
NCK1	0.028	0.002	-10000	0	-10000	0	0
fibronectin binding	0	0	0	44	0	18	62
endosomal lumen acidification	0	0	0	47	0	18	65
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.007	0.088	-10000	0	-0.36	33	33
GNAQ/ARNO	0.03	0.068	-10000	0	-0.92	3	3
mol:Phosphatidic acid	0	0	0	7	-10000	0	7
PIP3-E	0	0	0	16	0	7	23
MET	0.023	0.045	0.36	1	-0.44	5	6
GNA14	0.024	0.035	-10000	0	-0.36	5	5
GNA15	0.023	0.046	-10000	0	-0.44	6	6
GIT1	0.026	0.016	-10000	0	-0.36	1	1
mol:PI-4-5-P2	0	0	0.001	32	-0.001	27	59
GNA11	0.025	0.031	-10000	0	-0.36	4	4
LHCGR	-0.012	0.015	-10000	0	-10000	0	0
AGTR1	-0.12	0.18	-10000	0	-0.36	214	214
desensitization of G-protein coupled receptor protein signaling pathway	0.007	0.026	-10000	0	-10000	0	0
IPCEF1/ARNO	0.001	0.098	-10000	0	-0.89	3	3
alphaIIb/beta3 Integrin	0.023	0.074	-10000	0	-0.3	30	30

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.055	0.063	-10000	0	-10000	0	0
SMARCC2	0.025	0.017	-10000	0	-10000	0	0
SMARCC1	0.025	0.018	-10000	0	-10000	0	0
TBX21	-0.096	0.18	0.29	2	-0.64	43	45
SUMO2	0.027	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.033	0.019	-10000	0	-0.43	1	1
FKBP4	0.027	0.014	0.36	1	-10000	0	1
FKBP5	0.027	0.016	-10000	0	-0.36	1	1
GR alpha/HSP90/FKBP51/HSP90	0.087	0.1	0.29	21	-0.29	8	29
PRL	-0.041	0.087	-10000	0	-0.5	3	3
cortisol/GR alpha (dimer)/TIF2	0.16	0.19	0.49	69	-0.37	8	77
RELA	-0.039	0.073	-10000	0	-0.24	1	1
FGG	0.075	0.18	0.42	33	-0.42	26	59
GR beta/TIF2	0.074	0.11	0.29	25	-0.29	25	50
IFNG	-0.19	0.16	-10000	0	-0.6	40	40
apoptosis	-0.001	0.14	0.46	16	-0.51	8	24
CREB1	0.028	0.018	-10000	0	-10000	0	0
histone acetylation	-0.043	0.098	0.32	5	-0.33	23	28
BGLAP	-0.044	0.088	-10000	0	-0.44	2	2
GR/PKAc	0.066	0.13	0.29	15	-0.34	18	33
NF kappa B1 p50/RelA	-0.065	0.12	-10000	0	-0.31	37	37
SMARCD1	0.025	0.018	-10000	0	-10000	0	0
MDM2	0.057	0.059	0.21	34	-0.24	1	35
GATA3	0.023	0.044	-10000	0	-0.38	5	5
AKT1	0.022	0.006	-10000	0	-10000	0	0
CSF2	-0.12	0.12	-10000	0	-0.42	15	15
GSK3B	0.028	0.007	-10000	0	-10000	0	0
NR1I3	0.003	0.15	0.47	14	-0.68	6	20
CSN2	0.072	0.12	0.35	28	-0.36	5	33
BRG1/BAF155/BAF170/BAF60A	0.064	0.052	-10000	0	-0.26	4	4
NFATC1	0.019	0.03	-10000	0	-0.36	3	3
POU2F1	0.026	0.025	-10000	0	-0.44	1	1
CDKN1A	-0.009	0.085	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.006	-10000	0	-10000	0	0
SFN	0.025	0.023	-10000	0	-0.36	2	2
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.093	0.1	0.3	16	-0.28	5	21
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.001	0.13	0.44	13	-0.63	4	17
JUN	-0.18	0.12	-10000	0	-0.42	52	52
IL4	-0.05	0.083	-10000	0	-0.44	7	7
CDK5R1	0.027	0.02	-10000	0	-0.44	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.22	0.16	-10000	0	-0.41	166	166
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.097	0.1	0.3	17	-0.29	5	22
cortisol/GR alpha (monomer)	0.19	0.22	0.55	79	-0.45	5	84
NCOA2	0.022	0.028	-10000	0	-0.36	3	3
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.074	0.054	-10000	0	-0.38	7	7
AP-1/NFAT1-c-4	-0.28	0.17	-10000	0	-0.53	121	121
AFP	-0.13	0.11	-10000	0	-0.52	3	3
SUV420H1	0.027	0.004	-10000	0	-10000	0	0
IRF1	0.092	0.1	0.4	11	-10000	0	11
TP53	0.034	0.026	-10000	0	-0.48	1	1
PPP5C	0.027	0.004	-10000	0	-10000	0	0
KRT17	-0.32	0.18	-10000	0	-0.53	146	146
KRT14	-0.076	0.18	0.4	5	-0.92	16	21
TBP	0.033	0.011	-10000	0	-10000	0	0
CREBBP	0.034	0.069	0.32	9	-0.25	21	30
HDAC1	0.026	0.008	-10000	0	-10000	0	0
HDAC2	0.036	0.014	-10000	0	-10000	0	0
AP-1	-0.28	0.17	-10000	0	-0.54	122	122
MAPK14	0.028	0.007	-10000	0	-10000	0	0
MAPK10	-0.019	0.12	-10000	0	-0.36	73	73
MAPK11	0.025	0.029	-10000	0	-0.45	2	2
KRT5	-0.2	0.18	-10000	0	-0.56	77	77
interleukin-1 receptor activity	0.009	0.012	-10000	0	-10000	0	0
NCOA1	0.03	0.001	-10000	0	-10000	0	0
STAT1	0.033	0.019	-10000	0	-0.44	1	1
CGA	-0.055	0.094	-10000	0	-0.42	6	6
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.084	0.14	0.34	43	-0.39	15	58
MAPK3	0.027	0.017	-10000	0	-0.36	1	1
MAPK1	0.027	0.009	-10000	0	-10000	0	0
ICAM1	-0.1	0.14	-10000	0	-0.43	32	32
NFKB1	-0.039	0.073	-10000	0	-0.23	5	5
MAPK8	-0.13	0.11	-10000	0	-0.37	43	43
MAPK9	0.028	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.002	0.15	0.47	16	-0.53	8	24
BAX	-0.006	0.073	-10000	0	-10000	0	0
POMC	-0.099	0.25	-10000	0	-1.3	22	22
EP300	0.034	0.07	0.32	10	-0.25	21	31
cortisol/GR alpha (dimer)/p53	0.16	0.19	0.5	65	-0.41	3	68
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.059	0.26	20	-0.21	1	21
SGK1	0.001	0.26	0.37	4	-1.2	25	29
IL13	-0.14	0.13	-10000	0	-0.54	17	17
IL6	-0.13	0.19	-10000	0	-0.53	78	78
PRKACG	-0.006	0.032	-10000	0	-0.44	2	2
IL5	-0.12	0.11	-10000	0	-0.52	8	8
IL2	-0.18	0.14	-10000	0	-0.52	40	40
CDK5	0.027	0.006	-10000	0	-10000	0	0
PRKACB	-0.019	0.12	-10000	0	-0.36	72	72
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
IL8	-0.21	0.21	-10000	0	-0.48	132	132
CDK5R1/CDK5	0.039	0.019	-10000	0	-0.31	1	1
NF kappa B1 p50/RelA/PKAc	-0.056	0.12	-10000	0	-0.32	18	18
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.17	0.18	0.48	68	-0.37	4	72
SMARCA4	0.025	0.017	-10000	0	-10000	0	0
chromatin remodeling	0.081	0.15	0.34	35	-0.48	21	56
NF kappa B1 p50/RelA/Cbp	-0.011	0.13	0.35	6	-0.35	10	16
JUN (dimer)	-0.18	0.12	-10000	0	-0.42	52	52
YWHAH	0.027	0.006	-10000	0	-10000	0	0
VIPR1	-0.091	0.17	-10000	0	-0.69	34	34
NR3C1	0.093	0.15	0.38	45	-0.37	32	77
NR4A1	0.006	0.12	-10000	0	-0.5	30	30
TIF2/SUV420H1	0.034	0.025	-10000	0	-0.25	3	3
MAPKKK cascade	-0.001	0.14	0.46	16	-0.51	8	24
cortisol/GR alpha (dimer)/Src-1	0.18	0.19	0.49	78	-0.4	4	82
PBX1	0.019	0.058	-10000	0	-0.36	13	13
POU1F1	0.002	0.033	-10000	0	-0.53	1	1
SELE	-0.13	0.18	-10000	0	-0.48	87	87
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.081	0.15	0.34	35	-0.49	21	56
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.17	0.18	0.48	68	-0.37	4	72
mol:cortisol	0.093	0.11	0.3	79	-10000	0	79
MMP1	-0.24	0.17	-10000	0	-0.78	13	13

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.052	0.12	0.29	45	-10000	0	45
GNAI2	0.027	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.027	0.046	-10000	0	-0.27	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
RhoA/GTP	-0.052	0.12	-10000	0	-0.3	45	45
negative regulation of cAMP metabolic process	-0.063	0.12	-10000	0	-0.33	43	43
GNAZ	0.023	0.035	-10000	0	-0.36	5	5
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNA12	0.025	0.008	-10000	0	-10000	0	0
S1PR5	0.016	0.073	-10000	0	-0.44	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.063	0.12	-10000	0	-0.33	43	43
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
GNAI1	0.015	0.067	-10000	0	-0.36	19	19

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.027	0.004	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.001	0.098	-10000	0	-0.38	20	20
Syndecan-3/Neurocan	0.007	0.088	-10000	0	-0.37	30	30
POMC	0.011	0.075	-10000	0	-0.36	23	23
EGFR	0.024	0.023	-10000	0	-0.36	2	2
Syndecan-3/EGFR	0.008	0.087	-10000	0	-0.37	29	29
AGRP	-0.006	0.049	-10000	0	-0.44	6	6
NCSTN	0.027	0.004	-10000	0	-10000	0	0
PSENEN	0.026	0.016	-10000	0	-0.36	1	1
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.026	0.006	-10000	0	-10000	0	0
APH1A	0.027	0.004	-10000	0	-10000	0	0
NCAN	0.002	0.034	-10000	0	-0.44	2	2
long-term memory	0.027	0.088	-10000	0	-0.35	30	30
Syndecan-3/IL8	-0.12	0.14	0.23	2	-0.44	33	35
PSEN1	0.026	0.007	-10000	0	-10000	0	0
Src/Cortactin	0.024	0.02	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
limb bud formation	-0.005	0.084	-10000	0	-0.38	30	30
MC4R	-0.008	0.039	-10000	0	-0.44	4	4
SRC	0.017	0.014	-10000	0	-10000	0	0
PTN	-0.034	0.14	-10000	0	-0.36	95	95
FGFR/FGF/Syndecan-3	-0.006	0.085	-10000	0	-0.38	30	30
neuron projection morphogenesis	0.031	0.12	-10000	0	-0.37	20	20
Syndecan-3/AgRP	0.005	0.09	-10000	0	-0.37	30	30
Syndecan-3/AgRP/MC4R	0.008	0.089	-10000	0	-0.34	31	31
Fyn/Cortactin	0.039	0.009	-10000	0	-10000	0	0
SDC3	-0.006	0.086	-10000	0	-0.38	30	30
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.12	0.14	0.23	2	-0.43	33	35
IL8	-0.23	0.24	0.36	2	-0.44	338	340
Syndecan-3/Fyn/Cortactin	0.027	0.09	-10000	0	-0.36	30	30
Syndecan-3/CASK	-0.007	0.083	-10000	0	-0.36	30	30
alpha-MSH/MC4R	0.013	0.06	-10000	0	-0.26	27	27
Gamma Secretase	0.071	0.031	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.027	0.016	-9999	-0.36	1	1
EGFR	0.024	0.023	-9999	-0.36	2	2
EGF/EGFR	-0.011	0.11	-9999	-0.26	51	51
EGF/EGFR dimer/SHC/GRB2/SOS1	0.02	0.1	-9999	-0.23	20	20
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.003	0.12	-9999	-0.45	39	39
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.06	0.16	-9999	-0.37	127	127
EGF/EGFR dimer/SHC	-0.003	0.11	-9999	-0.22	113	113
mol:GDP	0.015	0.1	-9999	-0.23	20	20
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.027	0.016	-9999	-0.36	1	1
GRB2/SOS1	0.04	0.007	-9999	-10000	0	0
HRAS/GTP	0.002	0.088	-9999	-10000	0	0
SHC1	0.027	0.004	-9999	-10000	0	0
HRAS/GDP	0.015	0.098	-9999	-10000	0	0
FRAP1	-0.042	0.067	-9999	-0.22	20	20
EGF/EGFR dimer	-0.021	0.12	-9999	-0.26	115	115
SOS1	0.028	0.002	-9999	-10000	0	0
GRB2	0.027	0.004	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.016	0.089	-9999	-0.32	40	40

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.045	0.11	0.22	44	-0.3	7	51
PDGFB-D/PDGFRB/SLAP	0.03	0.045	-10000	0	-0.3	10	10
PDGFB-D/PDGFRB/APS/CBL	0.045	0.054	0.26	1	-0.26	16	17
AKT1	0.055	0.095	0.25	22	-10000	0	22
mol:PI-4-5-P2	0.001	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.067	0.13	0.24	76	-0.33	8	84
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
FGR	0.011	0.12	-10000	0	-0.46	26	26
mol:Ca2+	0.061	0.12	0.24	74	-0.42	5	79
MYC	0.09	0.16	0.39	78	-0.4	1	79
SHC1	0.027	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.063	0.076	-10000	0	-0.22	2	2
LRP1/PDGFRB/PDGFB	0.05	0.04	-10000	0	-0.25	9	9
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GO:0007205	0.061	0.12	0.24	73	-0.42	5	78
PTEN	0.026	0.006	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.035	0.049	0.36	14	-10000	0	14
PDGFB-D/PDGFRB/SHP2	0.038	0.038	-10000	0	-0.31	7	7
PDGFB-D/PDGFRB/GRB10	0.034	0.037	-10000	0	-0.31	6	6
cell cycle arrest	0.03	0.045	-10000	0	-0.29	10	10
HRAS	0.027	0.016	-10000	0	-0.36	1	1
HIF1A	0.048	0.088	0.24	22	-10000	0	22
GAB1	0.044	0.12	0.24	15	-0.34	9	24
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.058	0.12	0.23	88	-0.33	4	92
PDGFB-D/PDGFRB	0.026	0.042	-10000	0	-0.27	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.038	0.038	-10000	0	-0.31	7	7
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.004	0.062	-10000	0	-0.28	3	3
positive regulation of MAPKKK cascade	0.037	0.038	-10000	0	-0.31	7	7
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	0.061	0.12	0.24	73	-0.42	5	78
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.024	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.042	0.051	0.26	14	-0.31	7	21
SHB	0.026	0.03	0.36	1	-0.44	2	3
BLK	-0.14	0.23	-10000	0	-0.46	200	200
PTPN2	0.024	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.037	0.039	-10000	0	-0.31	7	7
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
VAV2	0.054	0.13	0.25	87	-0.38	7	94
CBL	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.038	0.038	-10000	0	-0.31	7	7
LCK	0.019	0.11	-10000	0	-0.44	18	18
PDGFRB	0.024	0.05	-10000	0	-0.44	7	7
ACP1	0.028	0.002	-10000	0	-10000	0	0
HCK	0.005	0.076	-10000	0	-0.48	10	10
ABL1	0.038	0.13	0.23	76	-0.34	15	91
PDGFB-D/PDGFRB/CBL	0.031	0.12	0.29	2	-0.42	9	11
PTPN1	0.016	0.014	-10000	0	-10000	0	0
SNX15	0.027	0.004	-10000	0	-10000	0	0
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.027	0.019	-10000	0	-0.44	1	1
cell proliferation	0.089	0.15	0.38	81	-0.36	1	82
SLA	0.022	0.029	-10000	0	-0.36	3	3
actin cytoskeleton reorganization	0.086	0.088	0.34	7	-10000	0	7
SRC	0.009	0.04	-10000	0	-10000	0	0
PI3K	-0.003	0.026	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.054	0.046	0.25	12	-0.26	7	19
SH2B2	0.02	0.058	0.36	1	-0.44	9	10
PLCgamma1/SPHK1	0.068	0.13	0.25	73	-0.34	8	81
LYN	0.023	0.077	-10000	0	-0.47	5	5
LRP1	0.026	0.022	-10000	0	-0.36	2	2
SOS1	0.028	0.002	-10000	0	-10000	0	0
STAT5B	0.027	0.004	-10000	0	-10000	0	0
STAT5A	0.027	0.004	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.04	0.051	-10000	0	-10000	0	0
SPHK1	0	0.12	-10000	0	-0.44	40	40
EDG1	0.003	0.004	-10000	0	-10000	0	0
mol:DAG	0.061	0.12	0.24	73	-0.42	5	78
PLCG1	0.061	0.12	0.24	73	-0.44	5	78
NHERF/PDGFRB	0.05	0.038	-10000	0	-0.26	8	8
YES1	-0.002	0.15	-10000	0	-0.51	39	39
cell migration	0.05	0.038	-10000	0	-0.26	8	8
SHC/Grb2/SOS1	0.038	0.05	-10000	0	-10000	0	0
SLC9A3R2	0.027	0.016	-10000	0	-0.36	1	1
SLC9A3R1	0.027	0.004	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.062	0.041	-10000	0	-0.23	8	8
FYN	0.019	0.093	-10000	0	-0.47	11	11
DOK1	0.057	0.083	0.18	183	-0.24	6	189
HRAS/GTP	0.02	0.011	-10000	0	-0.25	1	1
PDGFB	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.067	0.15	0.34	56	-0.45	3	59
PRKCD	0.057	0.085	0.18	178	-0.24	6	184
FER	0.056	0.086	0.18	175	-0.24	6	181
MAPKKK cascade	0.063	0.099	0.32	11	-10000	0	11
RASA1	0.058	0.086	0.18	176	-0.24	6	182
NCK1	0.028	0.002	-10000	0	-10000	0	0
NCK2	0.028	0.001	-10000	0	-10000	0	0
p62DOK/Csk	0.065	0.075	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.036	0.044	0.26	1	-0.31	9	10
chemotaxis	0.038	0.12	0.23	76	-0.33	15	91
STAT1-3-5/STAT1-3-5	0.032	0.044	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.018	0.036	-10000	0	-0.31	7	7
PTPRJ	0.028	0.003	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.017	0.072	-10000	0	-0.37	7	7
Syndecan-4/Syndesmos	0.026	0.13	0.32	8	-0.5	3	11
positive regulation of JNK cascade	0.001	0.14	0.3	8	-0.51	5	13
Syndecan-4/ADAM12	-0.07	0.18	0.35	3	-0.43	35	38
CCL5	0.012	0.075	-10000	0	-0.36	24	24
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
DNM2	0.027	0.003	-10000	0	-10000	0	0
ITGA5	0.026	0.027	-10000	0	-0.44	2	2
SDCBP	0.024	0.018	-10000	0	-0.36	1	1
PLG	-0.1	0.19	0.35	1	-0.46	127	128
ADAM12	-0.23	0.24	-10000	0	-0.45	330	330
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.043	0.05	-10000	0	-0.16	4	4
Syndecan-4/Laminin alpha1	-0.011	0.13	0.31	7	-0.45	5	12
Syndecan-4/CXCL12/CXCR4	0.002	0.15	0.32	8	-0.54	5	13
Syndecan-4/Laminin alpha3	0.016	0.12	0.31	9	-0.5	3	12
MDK	0.023	0.046	-10000	0	-0.44	6	6
Syndecan-4/FZD7	0.028	0.13	0.32	10	-0.47	4	14
Syndecan-4/Midkine	0.026	0.14	0.32	10	-0.49	3	13
FZD7	0.028	0	-10000	0	-10000	0	0
Syndecan-4/FGFR1/FGF	0.008	0.13	0.35	1	-0.48	3	4
THBS1	0.025	0.025	-10000	0	-0.4	2	2
integrin-mediated signaling pathway	0.023	0.13	0.31	9	-0.46	5	14
positive regulation of MAPKKK cascade	0.001	0.14	0.3	8	-0.51	5	13
Syndecan-4/TACI	-0.029	0.14	0.32	6	-0.41	17	23
CXCR4	0.028	0.002	-10000	0	-10000	0	0
cell adhesion	0.009	0.049	0.2	14	-0.22	8	22
Syndecan-4/Dynamin	0.028	0.13	0.32	10	-0.5	3	13
Syndecan-4/TSP1	0.027	0.13	0.32	10	-0.45	5	15
Syndecan-4/GIPC	0.028	0.13	0.32	10	-0.5	3	13
Syndecan-4/RANTES	0.021	0.14	0.32	9	-0.5	4	13
ITGB1	0.028	0.002	-10000	0	-10000	0	0
LAMA1	-0.054	0.15	-10000	0	-0.36	121	121
LAMA3	0.02	0.034	-10000	0	-0.38	4	4
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.02	0.12	0.79	15	-10000	0	15
Syndecan-4/alpha-Actinin	0.024	0.13	0.31	9	-0.47	4	13
TFPI	0.025	0.035	-10000	0	-0.36	5	5
F2	-0.12	0.22	-10000	0	-0.43	210	210
alpha5/beta1 Integrin	0.04	0.021	-10000	0	-0.32	2	2
positive regulation of cell adhesion	-0.018	0.13	0.3	7	-0.45	5	12
ACTN1	0.026	0.007	-10000	0	-10000	0	0
TNC	0.018	0.064	-10000	0	-0.4	14	14
Syndecan-4/CXCL12	0.004	0.14	0.32	8	-0.56	5	13
FGF6	-0.017	0.024	0.36	1	-0.44	1	2
RHOA	0.027	0.004	-10000	0	-10000	0	0
CXCL12	-0.046	0.15	-10000	0	-0.36	116	116
TNFRSF13B	-0.12	0.18	-10000	0	-0.36	214	214
FGF2	0	0.099	-10000	0	-0.36	43	43
FGFR1	0.021	0.032	-10000	0	-0.36	4	4
Syndecan-4/PI-4-5-P2	-0.015	0.099	0.29	7	-0.46	4	11
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.012	0.11	-10000	0	-0.43	36	36
cell migration	-0.022	0.02	-10000	0	-10000	0	0
PRKCD	0.015	0.024	-10000	0	-10000	0	0
vasculogenesis	0.027	0.13	0.32	10	-0.44	5	15
SDC4	-0.013	0.1	0.32	7	-0.49	4	11
Syndecan-4/Tenascin C	0.023	0.14	0.31	9	-0.48	5	14
Syndecan-4/PI-4-5-P2/PKC alpha	-0.035	0.038	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.02	0.12	0.32	7	-0.5	3	10
MMP9	-0.001	0.12	0.37	15	-0.44	32	47
Rac1/GTP	0.009	0.05	0.2	14	-0.22	8	22
cytoskeleton organization	0.026	0.13	0.31	8	-0.45	4	12
GIPC1	0.027	0.016	-10000	0	-0.36	1	1
Syndecan-4/TFPI	0.027	0.13	0.32	10	-0.5	3	13

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
CDC42/GTP	-0.054	0.12	-10000	0	-0.32	45	45
PLCG1	-0.042	0.1	-10000	0	-0.34	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
G12/G13	0.036	0.013	-10000	0	-10000	0	0
cell migration	-0.054	0.12	-10000	0	-0.32	45	45
S1PR5	0.016	0.073	-10000	0	-0.44	15	15
S1PR4	0.021	0.049	-10000	0	-0.36	10	10
MAPK3	-0.068	0.12	-10000	0	-0.33	49	49
MAPK1	-0.059	0.11	-10000	0	-0.35	33	33
S1P/S1P5/Gi	-0.063	0.12	-10000	0	-0.33	43	43
GNAI1	0.015	0.067	-10000	0	-0.36	19	19
CDC42/GDP	0.019	0.012	-10000	0	-0.25	1	1
S1P/S1P5/G12	0.027	0.046	-10000	0	-0.27	14	14
RHOA	0.027	0.058	0.19	60	-10000	0	60
S1P/S1P4/Gi	-0.063	0.13	-10000	0	-0.36	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.023	0.035	-10000	0	-0.36	5	5
S1P/S1P4/G12/G13	0.043	0.032	-10000	0	-0.19	7	7
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.025	0.017	-10000	0	-0.36	1	1

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.002	0.1	0.22	2	-0.33	27	29
TBX21	-0.086	0.38	-10000	0	-1.2	51	51
B2M	0.023	0.022	-10000	0	-0.36	1	1
TYK2	0.02	0.031	-10000	0	-10000	0	0
IL12RB1	0.008	0.079	-10000	0	-0.39	20	20
GADD45B	-0.028	0.26	-10000	0	-0.85	35	35
IL12RB2	0.012	0.066	-10000	0	-0.4	12	12
GADD45G	-0.029	0.26	-10000	0	-0.9	28	28
natural killer cell activation	0	0.018	0.046	8	-0.043	33	41
RELB	0.027	0.003	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
IL18	0.026	0.03	-10000	0	-0.36	3	3
IL2RA	0.019	0.056	-10000	0	-0.36	13	13
IFNG	-0.026	0.14	-10000	0	-0.44	60	60
STAT3 (dimer)	-0.032	0.26	0.34	2	-0.73	48	50
HLA-DRB5	0	0.002	-10000	0	-0.021	4	4
FASLG	-0.083	0.37	0.58	1	-1.1	52	53
NF kappa B2 p52/RelB	-0.05	0.3	-10000	0	-0.87	49	49
CD4	0.016	0.064	-10000	0	-0.36	17	17
SOCS1	0.011	0.086	-10000	0	-0.44	21	21
EntrezGene:6955	0	0.009	-10000	0	-0.036	30	30
CD3D	0.015	0.064	-10000	0	-0.36	16	16
CD3E	0.012	0.072	-10000	0	-0.36	21	21
CD3G	-0.004	0.1	-10000	0	-0.37	47	47
IL12Rbeta2/JAK2	0.024	0.066	-10000	0	-0.29	15	15
CCL3	-0.062	0.31	-10000	0	-0.94	44	44
CCL4	-0.057	0.3	-10000	0	-0.94	41	41
HLA-A	-0.001	0.008	-10000	0	-0.038	26	26
IL18/IL18R	0.051	0.084	-10000	0	-0.24	25	25
NOS2	-0.072	0.36	-10000	0	-1.2	46	46
IL12/IL12R/TYK2/JAK2/SPHK2	0.007	0.097	0.22	2	-0.33	24	26
IL1R1	-0.064	0.32	-10000	0	-0.98	45	45
IL4	-0.003	0.034	-10000	0	-10000	0	0
JAK2	0.017	0.042	-10000	0	-0.38	3	3
EntrezGene:6957	0	0.009	-10000	0	-0.038	28	28
TCR/CD3/MHC I/CD8	-0.054	0.25	-10000	0	-0.8	52	52
RAB7A	-0.019	0.23	0.52	1	-0.77	25	26
lysosomal transport	-0.016	0.22	0.51	1	-0.73	25	26
FOS	-0.061	0.29	-10000	0	-0.83	56	56
STAT4 (dimer)	-0.03	0.28	0.44	2	-0.82	46	48
STAT5A (dimer)	-0.067	0.31	-10000	0	-0.83	57	57
GZMA	-0.1	0.4	-10000	0	-1.2	61	61
GZMB	-0.086	0.31	-10000	0	-0.93	44	44
HLX	0.027	0.016	-10000	0	-0.36	1	1
LCK	-0.069	0.32	0.38	1	-0.92	53	54
TCR/CD3/MHC II/CD4	-0.017	0.14	-10000	0	-0.44	43	43
IL2/IL2R	0.05	0.065	-10000	0	-0.26	22	22
MAPK14	-0.031	0.28	-10000	0	-0.88	35	35
CCR5	-0.038	0.29	-10000	0	-1.1	26	26
IL1B	-0.023	0.14	-10000	0	-0.44	58	58
STAT6	0.007	0.091	-10000	0	-10000	0	0
STAT4	0.011	0.08	-10000	0	-0.36	27	27
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.027	0.019	-10000	0	-0.44	1	1
NFKB1	0.027	0.005	-10000	0	-10000	0	0
NFKB2	0.027	0.006	-10000	0	-10000	0	0
IL12B	0.012	0.05	-10000	0	-0.44	4	4
CD8A	-0.003	0.1	-10000	0	-0.37	45	45
CD8B	0.016	0.063	-10000	0	-0.37	15	15
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.002	0.1	0.33	27	-0.22	2	29
IL2RB	0.018	0.058	-10000	0	-0.36	14	14
proteasomal ubiquitin-dependent protein catabolic process	-0.023	0.26	0.43	2	-0.75	45	47
IL2RG	0.026	0.027	-10000	0	-0.36	3	3
IL12	0.022	0.065	-10000	0	-0.29	12	12
STAT5A	0.027	0.004	-10000	0	-10000	0	0
CD247	0.017	0.06	-10000	0	-0.36	14	14
IL2	-0.006	0.02	-10000	0	-10000	0	0
SPHK2	0.027	0.016	-10000	0	-0.36	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.014	0.056	-10000	0	-0.38	8	8
IL12/IL12R/TYK2/JAK2	-0.069	0.34	0.41	2	-0.98	53	55
MAP2K3	-0.051	0.3	-10000	0	-0.88	46	46
RIPK2	0.024	0.01	-10000	0	-10000	0	0
MAP2K6	-0.025	0.27	-10000	0	-0.86	34	34
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.001	0.002	-10000	0	-0.023	5	5
IL18RAP	0.009	0.086	-10000	0	-0.37	29	29
IL12Rbeta1/TYK2	0.022	0.07	-10000	0	-0.29	20	20
EOMES	-0.043	0.25	-10000	0	-1.1	32	32
STAT1 (dimer)	-0.029	0.25	0.35	2	-0.71	46	48
T cell proliferation	-0.012	0.22	0.38	2	-0.63	39	41
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.022	0.052	-10000	0	-0.37	10	10
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.019	0.24	-10000	0	-0.68	40	40
ATF2	-0.029	0.26	-10000	0	-0.83	32	32

×

Nectin adhesion pathway

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
PDGFRB	0.022	0.05	-10000	0	-0.44	7	7
alphaV beta3 Integrin	0.037	0.032	-10000	0	-0.25	7	7
PTK2	0.016	0.067	-10000	0	-0.34	13	13
positive regulation of JNK cascade	0.028	0.068	-10000	0	-0.28	11	11
CDC42/GDP	0.059	0.097	0.3	3	-0.36	11	14
Rac1/GDP	0.053	0.095	0.32	2	-0.36	11	13
RAP1B	0.028	0.003	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.047	0.084	-10000	0	-0.34	10	10
nectin-3/I-afadin	0.032	0.047	-10000	0	-0.25	16	16
RAPGEF1	0.034	0.091	0.3	4	-0.39	10	14
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.089	-10000	0	-0.44	10	10
PDGFB-D/PDGFRB	0.022	0.05	-10000	0	-0.44	7	7
TLN1	-0.001	0.025	-10000	0	-0.3	2	2
Rap1/GTP	0.022	0.065	-10000	0	-0.3	9	9
IQGAP1	0.027	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.013	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.032	0.047	-10000	0	-0.25	16	16
PVR	0.027	0.003	-10000	0	-10000	0	0
Necl-5(dimer)	0.027	0.003	-10000	0	-10000	0	0
mol:GDP	0.052	0.11	0.34	2	-0.43	11	13
MLLT4	0.027	0.004	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
PI3K	0.066	0.057	-10000	0	-0.23	7	7
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.039	0.008	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.029	0.077	-10000	0	-0.29	10	10
PVRL1	0.027	0.004	-10000	0	-10000	0	0
PVRL3	0.017	0.062	-10000	0	-0.36	16	16
PVRL2	0.027	0.003	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
CDH1	0.028	0.003	-10000	0	-10000	0	0
CLDN1	-0.4	0.14	0.36	3	-0.44	557	560
JAM-A/CLDN1	-0.22	0.096	-10000	0	-0.25	543	543
SRC	0.007	0.094	-10000	0	-0.45	16	16
ITGB3	0.023	0.041	-10000	0	-0.36	7	7
nectin-1(dimer)/I-afadin/I-afadin	0.039	0.008	-10000	0	-10000	0	0
FARP2	0.053	0.11	0.38	1	-0.44	11	12
RAC1	0.025	0.008	-10000	0	-10000	0	0
CTNNA1	0.027	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.047	0.044	-10000	0	-0.21	16	16
nectin-1/I-afadin	0.039	0.008	-10000	0	-10000	0	0
nectin-2/I-afadin	0.04	0.008	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.033	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.046	0.044	-10000	0	-0.21	16	16
CDC42/GTP/IQGAP1/filamentous actin	0.034	0.015	-10000	0	-0.21	1	1
F11R	0.027	0.004	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.028	0.068	-10000	0	-0.28	11	11
alphaV/beta3 Integrin/Talin	0.008	0.069	-10000	0	-0.28	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.04	0.008	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.04	0.008	-10000	0	-10000	0	0
PIP5K1C	0.002	0.028	-10000	0	-0.27	3	3
VAV2	0.047	0.12	0.36	1	-0.47	5	6
RAP1/GDP	0.061	0.09	0.25	4	-0.34	10	14
ITGAV	0.028	0.002	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.047	0.044	-10000	0	-0.21	16	16
nectin-3(dimer)/I-afadin/I-afadin	0.032	0.047	-10000	0	-0.25	16	16
Rac1/GTP	0.037	0.093	-10000	0	-0.35	10	10
PTPRM	0.007	0.034	-10000	0	-0.34	3	3
E-cadherin/beta catenin/alpha catenin	0.076	0.023	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.025	0.017	-10000	0	-0.36	1	1

×

HIF-2-alpha transcription factor network

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
MMP14	-0.029	0.16	-10000	0	-0.61	37	37
oxygen homeostasis	-0.01	0.01	-10000	0	-10000	0	0
TCEB2	0.026	0.027	-10000	0	-0.44	2	2
TCEB1	0.024	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.041	0.074	-10000	0	-10000	0	0
EPO	-0.14	0.16	-10000	0	-0.56	15	15
FIH (dimer)	0.008	0.023	-10000	0	-10000	0	0
APEX1	-0.014	0.024	-10000	0	-10000	0	0
SERPINE1	-0.19	0.23	-10000	0	-0.58	115	115
FLT1	-0.002	0.089	-10000	0	-0.62	10	10
ADORA2A	-0.15	0.17	0.36	1	-0.53	49	50
germ cell development	-0.15	0.17	-10000	0	-0.53	50	50
SLC11A2	-0.15	0.17	-10000	0	-0.55	48	48
BHLHE40	-0.15	0.18	-10000	0	-0.55	48	48
HIF1AN	0.008	0.023	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.084	0.11	-10000	0	-0.4	3	3
ETS1	0.036	0.018	-10000	0	-0.36	1	1
CITED2	-0.007	0.11	-10000	0	-0.71	12	12
KDR	-0.01	0.13	-10000	0	-0.64	20	20
PGK1	-0.15	0.17	-10000	0	-0.55	48	48
SIRT1	0.027	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.17	0.21	-10000	0	-0.62	50	50
EPAS1	-0.047	0.066	-10000	0	-0.3	4	4
SP1	0.031	0.01	-10000	0	-10000	0	0
ABCG2	-0.33	0.24	-10000	0	-0.62	146	146
EFNA1	-0.15	0.17	-10000	0	-0.55	49	49
FXN	-0.15	0.17	0.36	1	-0.53	48	49
POU5F1	-0.16	0.18	-10000	0	-0.55	50	50
neuron apoptosis	0.16	0.2	0.61	50	-10000	0	50
EP300	0.026	0.006	-10000	0	-10000	0	0
EGLN3	0.005	0.035	-10000	0	-0.36	3	3
EGLN2	0.008	0.028	-10000	0	-0.37	1	1
EGLN1	0.009	0.024	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.047	0.024	-10000	0	-0.27	1	1
VHL	0.027	0.004	-10000	0	-10000	0	0
ARNT	-0.013	0.029	-10000	0	-0.38	1	1
SLC2A1	-0.16	0.18	0.36	1	-0.56	54	55
TWIST1	-0.16	0.19	0.36	1	-0.64	47	48
ELK1	0.032	0.006	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.084	0.11	-10000	0	-0.39	3	3
VEGFA	-0.15	0.17	-10000	0	-0.55	46	46
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.04	0.019	0.26	2	-0.25	1	3
alphaV beta3 Integrin	0.032	0.076	-10000	0	-0.22	47	47
PTK2	0.031	0.11	0.26	36	-0.38	6	42
IGF1R	0.027	0.006	-10000	0	-10000	0	0
PI4KB	0.027	0.004	-10000	0	-10000	0	0
MFGE8	0.027	0.006	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
CDKN1B	0.01	0.044	-10000	0	-0.38	2	2
VEGFA	0.028	0.019	0.36	2	-10000	0	2
ILK	0.011	0.039	-10000	0	-10000	0	0
ROCK1	0.022	0.019	-10000	0	-0.36	1	1
AKT1	0.004	0.033	-10000	0	-10000	0	0
PTK2B	0.011	0.034	-10000	0	-10000	0	0
alphaV/beta3 Integrin/JAM-A	0.029	0.081	-10000	0	-0.24	20	20
CBL	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.045	0.037	-10000	0	-0.23	10	10
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.008	0.11	-10000	0	-0.19	131	131
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.016	0.038	-10000	0	-0.32	4	4
alphaV/beta3 Integrin/Syndecan-1	0.052	0.03	-10000	0	-0.21	7	7
PI4KA	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.021	0.14	-10000	0	-0.35	41	41
PI4 Kinase	0.039	0.01	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
alphaV/beta3 Integrin/Osteopontin	-0.088	0.16	-10000	0	-0.27	269	269
RPS6KB1	-0.069	0.1	-10000	0	-0.34	41	41
TLN1	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.043	0.15	-10000	0	-0.48	54	54
GPR124	0.023	0.018	-10000	0	-0.36	1	1
MAPK1	-0.042	0.15	-10000	0	-0.48	54	54
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.028	0.081	-10000	0	-0.22	57	57
cell adhesion	0.04	0.036	-10000	0	-0.22	7	7
ANGPTL3	-0.003	0.038	-10000	0	-0.44	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.033	0.029	0.25	1	-10000	0	1
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
TGFBR2	0.027	0.003	-10000	0	-10000	0	0
ITGB3	0.023	0.041	-10000	0	-0.36	7	7
IGF1	-0.062	0.16	-10000	0	-0.36	141	141
RAC1	0.025	0.008	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.044	0.035	-10000	0	-0.2	8	8
apoptosis	0.028	0.002	-10000	0	-10000	0	0
CD47	0.027	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.051	0.03	-10000	0	-0.21	7	7
VCL	0.027	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.006	0.11	-10000	0	-0.22	104	104
CSF1	0.025	0.027	-10000	0	-0.36	3	3
PIK3C2A	0.01	0.045	-10000	0	-0.38	2	2
PI4 Kinase/Pyk2	0.01	0.067	-10000	0	-0.31	2	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.064	0.035	0.26	2	-10000	0	2
FAK1/Vinculin	0.045	0.1	0.23	49	-0.33	4	53
alphaV beta3/Integrin/ppsTEM5	0.044	0.035	-10000	0	-0.2	8	8
RHOA	0.027	0.004	-10000	0	-10000	0	0
VTN	0.006	0.082	-10000	0	-0.44	19	19
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
FGF2	0	0.099	-10000	0	-0.36	43	43
F11R	-0.005	0.067	-10000	0	-0.25	42	42
alphaV/beta3 Integrin/Lactadherin	0.05	0.031	-10000	0	-0.21	7	7
alphaV/beta3 Integrin/TGFBR2	0.051	0.03	-10000	0	-0.21	7	7
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.065	0.027	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.048	0.028	-10000	0	-0.19	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.001	0.11	-10000	0	-0.43	36	36
alphaV/beta3 Integrin/Pyk2	0.037	0.039	-10000	0	-10000	0	0
SDC1	0.028	0	-10000	0	-10000	0	0
VAV3	-0.004	0.056	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
IRS1	0.028	0.002	-10000	0	-10000	0	0
FAK1/Paxillin	0.044	0.1	0.23	38	-0.34	3	41
cell migration	0.039	0.095	0.21	53	-0.31	3	56
ITGAV	0.028	0.002	-10000	0	-10000	0	0
PI3K	0.041	0.083	-10000	0	-0.33	2	2
SPP1	-0.18	0.23	-10000	0	-0.44	263	263
KDR	0.026	0.016	-10000	0	-0.36	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.028	0.002	-10000	0	-10000	0	0
COL4A3	-0.013	0.11	-10000	0	-0.38	51	51
angiogenesis	-0.038	0.15	0.24	1	-0.48	55	56
Rac1/GTP	0.009	0.055	-10000	0	-10000	0	0
EDIL3	-0.04	0.15	-10000	0	-0.36	106	106
cell proliferation	0.051	0.03	-10000	0	-0.21	7	7

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.006	0.11	-10000	0	-0.46	29	29
NFATC2	-0.004	0.12	-10000	0	-0.56	10	10
NFATC3	-0.018	0.066	-10000	0	-0.29	5	5
CD40LG	-0.18	0.27	-10000	0	-0.83	36	36
ITCH	0.018	0.018	-10000	0	-10000	0	0
CBLB	0.029	0.026	-10000	0	-0.36	2	2
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.11	0.2	-10000	0	-0.81	24	24
JUNB	0.026	0.022	-10000	0	-0.36	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.037	0.023	-10000	0	-0.26	3	3
T cell anergy	0.037	0.055	0.24	1	-0.31	1	2
TLE4	-0.003	0.084	-10000	0	-0.48	6	6
Jun/NFAT1-c-4/p21SNFT	-0.078	0.18	-10000	0	-0.78	10	10
AP-1/NFAT1-c-4	-0.2	0.27	-10000	0	-0.9	29	29
IKZF1	-0.014	0.13	-10000	0	-0.62	21	21
T-helper 2 cell differentiation	-0.052	0.16	0.4	1	-0.67	20	21
AP-1/NFAT1	-0.033	0.1	-10000	0	-0.42	6	6
CALM1	0.034	0.017	-10000	0	-10000	0	0
EGR2	-0.039	0.16	-10000	0	-1.1	7	7
EGR3	-0.041	0.17	-10000	0	-0.99	11	11
NFAT1/FOXP3	-0.002	0.12	-10000	0	-0.49	14	14
EGR1	0.027	0.023	-10000	0	-0.36	2	2
JUN	-0.032	0.047	-10000	0	-10000	0	0
EGR4	-0.052	0.17	-10000	0	-0.44	102	102
mol:Ca2+	0.009	0.011	-10000	0	-0.18	1	1
GBP3	-0.024	0.15	-10000	0	-0.58	34	34
FOSL1	-0.27	0.23	0.36	1	-0.44	385	386
NFAT1-c-4/MAF/IRF4	-0.069	0.18	-10000	0	-0.79	17	17
DGKA	-0.003	0.082	-10000	0	-0.44	6	6
CREM	0.027	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.042	0.15	-10000	0	-0.81	7	7
CTLA4	-0.017	0.11	-10000	0	-0.49	21	21
NFAT1-c-4 (dimer)/EGR1	-0.04	0.15	-10000	0	-0.81	7	7
NFAT1-c-4 (dimer)/EGR4	-0.072	0.17	-10000	0	-0.85	8	8
FOS	-0.033	0.057	-10000	0	-0.37	6	6
IFNG	-0.062	0.18	-10000	0	-0.73	18	18
T cell activation	-0.021	0.14	-10000	0	-0.57	2	2
MAF	0.019	0.058	-10000	0	-0.36	14	14
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.038	0.13	0.88	8	-10000	0	8
TNF	-0.067	0.15	-10000	0	-0.81	9	9
FASLG	-0.085	0.34	-10000	0	-1.2	44	44
TBX21	-0.002	0.094	-10000	0	-0.36	35	35
BATF3	0.022	0.049	-10000	0	-0.43	7	7
PRKCQ	0.019	0.052	-10000	0	-0.36	8	8
PTPN1	-0.003	0.082	-10000	0	-0.44	6	6
NFAT1-c-4/ICER1	-0.041	0.15	-10000	0	-0.81	7	7
GATA3	0.024	0.037	-10000	0	-0.38	5	5
T-helper 1 cell differentiation	-0.06	0.18	-10000	0	-0.72	18	18
IL2RA	-0.1	0.2	-10000	0	-0.76	28	28
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.004	0.08	-10000	0	-0.44	6	6
E2F1	0.021	0.057	0.36	9	-0.44	4	13
PPARG	0.026	0.022	-10000	0	-0.36	2	2
SLC3A2	-0.003	0.08	-10000	0	-0.44	6	6
IRF4	-0.072	0.17	-10000	0	-0.36	156	156
PTGS2	-0.18	0.27	-10000	0	-0.81	41	41
CSF2	-0.25	0.32	-10000	0	-0.76	80	80
JunB/Fra1/NFAT1-c-4	-0.16	0.18	-10000	0	-0.78	16	16
IL4	-0.054	0.17	0.4	1	-0.7	19	20
IL5	-0.17	0.26	-10000	0	-0.79	33	33
IL2	-0.022	0.14	-10000	0	-0.58	2	2
IL3	-0.033	0.089	-10000	0	-0.67	8	8
RNF128	0.029	0.026	-10000	0	-0.36	2	2
NFATC1	-0.038	0.14	-10000	0	-0.88	8	8
CDK4	0.023	0.096	0.64	4	-10000	0	4
PTPRK	-0.004	0.081	-10000	0	-0.45	5	5
IL8	-0.28	0.32	-10000	0	-0.77	81	81
POU2F1	0.026	0.02	-10000	0	-0.44	1	1

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.037	0.1	-10000	0	-0.33	37	37
ACTA1	-0.054	0.1	-10000	0	-0.34	34	34
NUMA1	-0.037	0.11	-10000	0	-0.36	38	38
SPTAN1	-0.054	0.1	0.21	1	-0.34	33	34
LIMK1	-0.048	0.11	0.29	5	-0.35	28	33
BIRC3	0.02	0.05	-10000	0	-0.37	10	10
BIRC2	0.026	0.016	-10000	0	-0.36	1	1
BAX	0.027	0.004	-10000	0	-10000	0	0
CASP10	-0.078	0.12	-10000	0	-0.28	153	153
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.028	0.002	-10000	0	-10000	0	0
PTK2	-0.035	0.11	-10000	0	-0.33	40	40
DIABLO	0.028	0.003	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.053	0.1	0.21	1	-0.33	33	34
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.027	0.003	-10000	0	-10000	0	0
GSN	-0.057	0.11	0.21	1	-0.34	37	38
MADD	0.028	0.003	-10000	0	-10000	0	0
TFAP2A	-0.001	0.095	0.35	1	-0.57	13	14
BID	-0.028	0.064	-10000	0	-0.22	25	25
MAP3K1	-0.02	0.08	-10000	0	-0.43	16	16
TRADD	0.028	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.039	0.01	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.053	0.1	0.28	2	-0.34	33	35
CASP9	0.026	0.007	-10000	0	-10000	0	0
DNA repair	0.009	0.04	0.18	4	-0.14	3	7
neuron apoptosis	-0.021	0.17	-10000	0	-0.66	37	37
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.048	0.11	-10000	0	-0.34	44	44
APAF1	0.028	0.003	-10000	0	-10000	0	0
CASP6	-0.025	0.16	0.34	1	-0.87	19	20
TRAF2	0.027	0.016	-10000	0	-0.36	1	1
ICAD/CAD	-0.054	0.097	-10000	0	-0.34	29	29
CASP7	0.002	0.056	0.23	6	-0.25	12	18
KRT18	0.011	0.038	-10000	0	-0.51	1	1
apoptosis	-0.051	0.12	0.31	1	-0.37	41	42
DFFA	-0.055	0.1	-10000	0	-0.34	33	33
DFFB	-0.055	0.1	0.19	1	-0.34	33	34
PARP1	-0.009	0.04	0.14	3	-0.18	4	7
actin filament polymerization	0.048	0.1	0.33	29	-0.27	3	32
TNF	0.024	0.035	-10000	0	-0.36	5	5
CYCS	-0.014	0.056	0.19	1	-0.17	16	17
SATB1	-0.027	0.15	0.32	1	-0.81	19	20
SLK	-0.055	0.1	-10000	0	-0.34	35	35
p15 BID/BAX	-0.018	0.07	-10000	0	-0.22	20	20
CASP2	0.021	0.045	0.21	16	-0.22	1	17
JNK cascade	0.019	0.079	0.43	16	-10000	0	16
CASP3	-0.056	0.11	-10000	0	-0.35	34	34
LMNB2	0.011	0.11	0.41	3	-0.62	10	13
RIPK1	0.027	0.004	-10000	0	-10000	0	0
CASP4	0.027	0.004	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.064	0.038	-10000	0	-0.24	1	1
negative regulation of DNA binding	-0.001	0.094	0.34	1	-0.56	13	14
stress fiber formation	-0.055	0.1	-10000	0	-0.33	35	35
GZMB	-0.074	0.15	-10000	0	-0.34	153	153
CASP1	0.013	0.019	-10000	0	-0.26	3	3
LMNB1	0.007	0.11	0.41	3	-0.55	14	17
APP	-0.022	0.17	-10000	0	-0.68	37	37
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.007	0	-10000	0	-10000	0	0
VIM	-0.048	0.12	0.32	1	-0.38	39	40
LMNA	0.018	0.069	0.4	3	-0.31	4	7
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.022	0.034	-10000	0	-0.23	2	2
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.051	0.098	-10000	0	-0.34	30	30
APAF-1/Caspase 9	-0.02	0.14	-10000	0	-0.61	33	33
nuclear fragmentation during apoptosis	-0.037	0.11	-10000	0	-0.35	38	38
CFL2	-0.049	0.1	0.3	2	-0.34	29	31
GAS2	-0.085	0.13	-10000	0	-0.38	67	67
positive regulation of apoptosis	0.016	0.099	0.36	4	-0.45	17	21
PRF1	0.019	0.058	-10000	0	-0.39	12	12

×

Noncanonical Wnt signaling pathway

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
NFATC2	0.005	0.063	-10000	0	-0.36	17	17
GNB1/GNG2	-0.028	0.12	-10000	0	-0.33	25	25
mol:DAG	-0.026	0.082	0.19	1	-0.34	15	16
PLCG1	-0.027	0.084	0.19	1	-0.34	15	16
YES1	-0.035	0.091	-10000	0	-0.3	30	30
FZD3	0.021	0.035	0.36	2	-0.44	2	4
FZD6	0.024	0.01	-10000	0	-10000	0	0
G protein	0.021	0.13	0.28	13	-0.38	12	25
MAP3K7	-0.033	0.076	0.16	1	-0.32	17	18
mol:Ca2+	-0.026	0.08	0.19	1	-0.33	15	16
mol:IP3	-0.026	0.082	0.19	1	-0.34	15	16
NLK	-0.003	0.094	-10000	0	-0.77	9	9
GNB1	0.026	0.006	-10000	0	-10000	0	0
CAMK2A	-0.032	0.082	0.18	1	-0.34	17	18
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.032	0.1	0.17	1	-0.3	44	45
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
GNAS	-0.021	0.086	0.33	1	-0.32	22	23
GO:0007205	-0.029	0.08	-10000	0	-0.35	12	12
WNT6	-0.011	0.11	-10000	0	-0.38	52	52
WNT4	0.013	0.072	-10000	0	-0.38	20	20
NFAT1/CK1 alpha	-0.019	0.092	-10000	0	-0.39	12	12
GNG2	0.011	0.074	-10000	0	-0.36	23	23
WNT5A	0.022	0.05	-10000	0	-0.44	7	7
WNT11	-0.069	0.19	-10000	0	-0.44	127	127
CDC42	-0.034	0.087	0.19	1	-0.33	14	15

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.028	0.002	-9999	-10000	0	0
ITGB7	0.013	0.074	-9999	-0.36	23	23
ITGA4	0.014	0.072	-9999	-0.36	22	22
alpha4/beta7 Integrin	0.02	0.081	-9999	-0.28	40	40
alpha4/beta1 Integrin	0.03	0.055	-9999	-0.25	22	22

×

Regulation of Androgen receptor activity

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
HDAC1	0.008	0.012	-10000	0	-10000	0	0
SMARCC1	0.013	0.01	-10000	0	-10000	0	0
REL	0.03	0.008	-10000	0	-10000	0	0
HDAC7	-0.023	0.082	-10000	0	-0.38	3	3
JUN	0.026	0.006	-10000	0	-10000	0	0
EP300	0.026	0.006	-10000	0	-10000	0	0
KAT2B	0.01	0.078	-10000	0	-0.36	26	26
KAT5	0.027	0.005	-10000	0	-10000	0	0
MAPK14	0.001	0.03	-10000	0	-0.27	4	4
FOXO1	0.02	0.019	-10000	0	-0.36	1	1
T-DHT/AR	-0.004	0.097	-10000	0	-0.4	3	3
MAP2K6	0.016	0.037	-10000	0	-0.37	4	4
BRM/BAF57	0.028	0.031	-10000	0	-0.28	1	1
MAP2K4	0.016	0.02	-10000	0	-10000	0	0
SMARCA2	0.019	0.025	-10000	0	-0.38	1	1
PDE9A	-0.15	0.38	-10000	0	-0.94	108	108
NCOA2	0.022	0.028	-10000	0	-0.36	3	3
CEBPA	0.026	0.027	-10000	0	-0.36	3	3
EHMT2	0.026	0.015	0.36	1	-10000	0	1
cell proliferation	0.034	0.13	0.28	38	-0.4	3	41
NR0B1	-0.005	0.045	-10000	0	-0.44	5	5
EGR1	0.019	0.028	-10000	0	-0.36	2	2
RXRs/9cRA	-0.059	0.12	-10000	0	-0.19	252	252
AR/RACK1/Src	0.051	0.099	0.27	10	-0.33	1	11
AR/GR	-0.019	0.089	-10000	0	-0.28	25	25
GNB2L1	0.027	0.004	-10000	0	-10000	0	0
PKN1	0.027	0.003	-10000	0	-10000	0	0
RCHY1	0.027	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-10000	0	-0.011	2	2
MAPK8	0.003	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.004	0.061	-10000	0	-0.34	1	1
SRC	0.024	0.083	0.19	118	-10000	0	118
NR3C1	-0.001	0.1	-10000	0	-0.36	44	44
KLK3	-0.21	0.42	-10000	0	-1.1	102	102
APPBP2	0.018	0.025	-10000	0	-0.36	1	1
TRIM24	0.02	0.019	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.005	0.057	0.2	3	-0.3	3	6
TMPRSS2	-0.023	0.15	-10000	0	-0.76	13	13
RXRG	-0.15	0.18	-10000	0	-0.36	253	253
mol:9cRA	-0.001	0.002	-10000	0	-0.01	3	3
RXRA	0.026	0.016	-10000	0	-0.36	1	1
RXRB	0.027	0.004	-10000	0	-10000	0	0
CARM1	0.028	0.003	-10000	0	-10000	0	0
NR2C2	0.026	0.016	-10000	0	-0.36	1	1
KLK2	0.021	0.091	0.28	2	-0.36	3	5
AR	-0.011	0.063	0.16	2	-0.24	37	39
SENP1	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
MDM2	0.031	0.02	-10000	0	-0.36	1	1
SRY	0.004	0.011	0.028	105	-10000	0	105
GATA2	0.021	0.052	-10000	0	-0.36	11	11
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	-0.008	0.099	-10000	0	-0.36	42	42
T-DHT/AR/RACK1/Src	0.06	0.1	0.28	13	-0.34	1	14
positive regulation of transcription	0.021	0.051	-10000	0	-0.36	11	11
DNAJA1	0.019	0.02	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.014	-10000	0	-0.28	1	1
NCOA1	0.025	0.02	-10000	0	-10000	0	0
SPDEF	-0.065	0.16	-10000	0	-0.36	138	138
T-DHT/AR/TIF2	-0.003	0.068	0.26	3	-0.3	3	6
T-DHT/AR/Hsp90	-0.006	0.054	0.2	2	-0.3	3	5
GSK3B	0.027	0.004	-10000	0	-10000	0	0
NR2C1	0.028	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.016	0.033	0.22	2	-0.25	3	5
SIRT1	0.027	0.005	-10000	0	-10000	0	0
ZMIZ2	0.029	0.015	-10000	0	-10000	0	0
POU2F1	0.015	0.055	-10000	0	-0.26	3	3
T-DHT/AR/DAX-1	-0.014	0.058	-10000	0	-0.3	4	4
CREBBP	0.027	0.004	-10000	0	-10000	0	0
SMARCE1	0.019	0.019	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.05	-10000	0	-0.44	7	7
Jak2/Leptin Receptor	0.022	0.087	-10000	0	-0.37	11	11
PTP1B/AKT1	0.017	0.078	0.18	3	-0.33	6	9
FYN	0.027	0.005	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.012	0.084	0.2	14	-0.34	7	21
EGFR	0.017	0.029	-10000	0	-0.37	2	2
EGF/EGFR	-0.013	0.11	-10000	0	-0.27	43	43
CSF1	0.025	0.027	-10000	0	-0.36	3	3
AKT1	0.026	0.008	-10000	0	-10000	0	0
INSR	0.028	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.007	0.08	0.2	6	-0.32	10	16
Insulin Receptor/Insulin	0.025	0.074	-10000	0	-0.38	3	3
HCK	0.011	0.047	-10000	0	-0.36	9	9
CRK	0.023	0.01	-10000	0	-10000	0	0
TYK2	0.01	0.082	0.24	11	-0.33	6	17
EGF	-0.057	0.16	-10000	0	-0.38	127	127
YES1	0.022	0.019	-10000	0	-0.36	1	1
CAV1	0.02	0.11	0.22	49	-0.32	7	56
TXN	0.027	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.027	0.087	-10000	0	-0.36	4	4
cell migration	-0.012	0.084	0.34	7	-0.2	14	21
STAT3	0.027	0.004	-10000	0	-10000	0	0
PRLR	0.017	0.062	-10000	0	-0.36	16	16
ITGA2B	0.006	0.089	-10000	0	-0.44	23	23
CSF1R	0.006	0.088	-10000	0	-0.36	33	33
Prolactin Receptor/Prolactin	0.02	0.069	-10000	0	-0.29	27	27
FGR	0.023	0.034	-10000	0	-0.38	4	4
PTP1B/p130 Cas	0.018	0.084	0.2	8	-0.34	6	14
Crk/p130 Cas	0.018	0.081	-10000	0	-0.33	5	5
DOK1	0.014	0.077	0.21	3	-0.37	4	7
JAK2	0.014	0.088	0.23	2	-0.35	14	16
Jak2/Leptin Receptor/Leptin	0.01	0.097	-10000	0	-0.33	5	5
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
PTPN1	0.012	0.084	0.2	14	-0.34	7	21
LYN	0.024	0.009	-10000	0	-10000	0	0
CDH2	0.005	0.077	-10000	0	-0.37	24	24
SRC	0.026	0.088	-10000	0	-0.41	15	15
ITGB3	0.022	0.042	-10000	0	-0.36	7	7
CAT1/PTP1B	0.005	0.16	0.24	80	-0.4	24	104
CAPN1	0.027	0.005	-10000	0	-10000	0	0
CSK	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.04	0.07	-10000	0	-0.41	2	2
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.014	0.089	-10000	0	-0.32	3	3
negative regulation of transcription	0.014	0.087	0.23	2	-0.35	14	16
FCGR2A	0.023	0.041	-10000	0	-0.43	5	5
FER	0.024	0.025	-10000	0	-0.4	2	2
alphaIIb/beta3 Integrin	0.022	0.074	-10000	0	-0.3	30	30
BLK	-0.09	0.17	-10000	0	-0.36	172	172
Insulin Receptor/Insulin/Shc	0.046	0.013	-10000	0	-10000	0	0
RHOA	0.027	0.005	-10000	0	-10000	0	0
LEPR	0.022	0.044	-10000	0	-0.36	8	8
BCAR1	0.027	0.016	-10000	0	-0.36	1	1
p210 bcr-abl/Grb2	0.027	0.004	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.065	0.17	0.24	18	-0.39	77	95
PRL	-0.005	0.066	-10000	0	-0.44	12	12
SOCS3	0.009	0.12	-10000	0	-1.1	8	8
SPRY2	0.023	0.012	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.047	0.012	-10000	0	-10000	0	0
CSF1/CSF1R	0.018	0.097	0.22	4	-0.33	11	15
Ras protein signal transduction	-0.006	0.051	0.43	6	-10000	0	6
IRS1	0.028	0.002	-10000	0	-10000	0	0
INS	0.003	0.018	-10000	0	-10000	0	0
LEP	-0.021	0.11	-10000	0	-0.37	54	54
STAT5B	0.018	0.082	0.2	10	-0.33	9	19
STAT5A	0.018	0.082	0.19	12	-0.33	9	21
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.017	0.089	0.19	12	-0.31	12	24
CSN2	-0.007	0.051	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
LAT	0.029	0.058	-10000	0	-0.45	5	5
YBX1	0.036	0.008	-10000	0	-10000	0	0
LCK	0.019	0.058	-10000	0	-0.43	10	10
SHC1	0.027	0.004	-10000	0	-10000	0	0
NOX4	-0.19	0.24	0.35	1	-0.44	280	281

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.011	-10000	0	-0.25	1	1
MAP4K4	0.017	0.037	-10000	0	-0.26	1	1
BAG4	0.024	0.01	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.014	0.073	-10000	0	-0.21	59	59
NFKBIA	0.026	0.007	-10000	0	-10000	0	0
BIRC3	0.021	0.05	-10000	0	-0.37	10	10
BAX	-0.003	0.041	-10000	0	-0.3	6	6
RIPK1	0.027	0.004	-10000	0	-10000	0	0
AKT1	-0.002	0.012	-10000	0	-10000	0	0
BAD	-0.03	0.067	-10000	0	-0.21	60	60
SMPD1	0.02	0.047	0.22	7	-0.22	5	12
RB1	0.01	0.087	0.19	80	-0.2	29	109
FADD/Caspase 8	0.024	0.04	0.2	2	-10000	0	2
MAP2K4	-0.028	0.063	-10000	0	-0.21	46	46
NSMAF	0.024	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.025	0.069	0.18	13	-0.21	42	55
EGF	-0.06	0.16	-10000	0	-0.37	127	127
mol:ceramide	-0.029	0.071	-10000	0	-0.22	60	60
MADD	0.028	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.01	0.006	-10000	0	-10000	0	0
ASAH1	0.021	0.012	-10000	0	-10000	0	0
negative regulation of cell cycle	0.01	0.087	0.19	80	-0.2	29	109
cell proliferation	-0.036	0.096	-10000	0	-0.31	17	17
BID	0	0.13	-10000	0	-0.58	27	27
MAP3K1	-0.03	0.067	-10000	0	-0.21	61	61
EIF2A	-0.031	0.062	0.18	1	-0.26	16	17
TRADD	0.028	0.003	-10000	0	-10000	0	0
CRADD	0.027	0.003	-10000	0	-10000	0	0
MAPK3	-0.021	0.066	0.18	5	-0.26	13	18
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.025	0.067	0.18	3	-0.26	14	17
Cathepsin D/ceramide	-0.015	0.074	-10000	0	-0.21	60	60
FADD	0.018	0.036	0.21	2	-10000	0	2
KSR1	-0.024	0.072	0.19	11	-0.21	56	67
MAPK8	-0.024	0.071	-10000	0	-0.24	24	24
PRKRA	-0.03	0.067	-10000	0	-0.21	60	60
PDGFA	0.025	0.008	-10000	0	-10000	0	0
TRAF2	0.027	0.016	-10000	0	-0.36	1	1
IGF1	-0.062	0.16	-10000	0	-0.36	141	141
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.029	0.071	-10000	0	-0.22	60	60
CTSD	0.027	0.016	-10000	0	-0.36	1	1
regulation of nitric oxide biosynthetic process	0.039	0.009	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.037	0.1	-10000	0	-0.33	17	17
PRKCD	0.027	0.004	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.006	-10000	0	-10000	0	0
RelA/NF kappa B1	0.039	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.028	0.003	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.023	0.031	-10000	0	-0.26	2	2
TNFR1A/BAG4/TNF-alpha	0.045	0.031	-10000	0	-0.21	5	5
mol:Sphingosine-1-phosphate	0.012	0.011	-10000	0	-0.25	1	1
MAP2K1	-0.025	0.066	0.19	4	-0.26	14	18
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
CYCS	0.02	0.051	0.15	8	-0.18	3	11
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.035	0.015	-10000	0	-10000	0	0
EIF2AK2	-0.031	0.064	-10000	0	-0.21	50	50
TNF-alpha/TNFR1A/FAN	0.046	0.03	-10000	0	-0.21	5	5
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.052	-10000	0	-0.32	3	3
MAP2K2	-0.025	0.066	0.18	4	-0.26	14	18
SMPD3	0.017	0.056	0.17	2	-0.28	15	17
TNF	0.024	0.035	-10000	0	-0.36	5	5
PKC zeta/PAR4	0.039	0.01	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.029	0.08	0.18	96	-0.16	4	100
NF kappa B1/RelA/I kappa B alpha	0.07	0.03	-10000	0	-10000	0	0
AIFM1	0.013	0.06	0.14	8	-0.17	10	18
BCL2	0.014	0.05	-10000	0	-0.36	10	10

×

S1P3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.05	-10000	0	-0.44	7	7
mol:S1P	0.001	0.002	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.055	0.11	-10000	0	-0.31	46	46
GNAO1	-0.11	0.19	-10000	0	-0.36	225	225
S1P/S1P3/G12/G13	0.046	0.024	-10000	0	-0.24	1	1
AKT1	-0.034	0.14	-10000	0	-0.47	48	48
AKT3	-0.012	0.15	-10000	0	-1.1	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.022	0.05	-10000	0	-0.44	7	7
GNAI2	0.027	0.009	-10000	0	-10000	0	0
GNAI3	0.027	0.008	-10000	0	-10000	0	0
GNAI1	0.015	0.068	-10000	0	-0.36	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.027	0.021	-10000	0	-0.44	1	1
S1PR2	0.027	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.13	-10000	0	-0.34	47	47
MAPK3	-0.059	0.12	-10000	0	-0.33	52	52
MAPK1	-0.051	0.12	-10000	0	-0.34	36	36
JAK2	-0.012	0.14	0.23	6	-0.38	27	33
CXCR4	-0.058	0.12	-10000	0	-0.33	51	51
FLT1	0.021	0.015	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
SRC	-0.039	0.1	-10000	0	-0.33	33	33
S1P/S1P3/Gi	-0.056	0.13	-10000	0	-0.35	47	47
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.046	0.13	-10000	0	-0.35	34	34
VEGFA	0.029	0.021	0.36	2	-10000	0	2
S1P/S1P2/Gi	-0.058	0.12	-10000	0	-0.33	48	48
VEGFR1 homodimer/VEGFA homodimer	0.033	0.025	0.26	1	-10000	0	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.021	0.04	-10000	0	-0.26	9	9
GNAQ	0.026	0.022	-10000	0	-0.36	2	2
GNAZ	0.023	0.036	-10000	0	-0.36	5	5
G12/G13	0.036	0.013	-10000	0	-10000	0	0
GNA14	0.024	0.035	-10000	0	-0.36	5	5
GNA15	0.023	0.046	-10000	0	-0.44	6	6
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.031	-10000	0	-0.36	4	4
Rac1/GTP	-0.045	0.12	-10000	0	-0.32	48	48

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.026	0.006	-10000	0	-10000	0	0
HDAC4	0.028	0.002	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.007	0.039	0.31	8	-0.27	1	9
CDKN1A	-0.008	0.024	-10000	0	-0.59	1	1
KAT2B	0.011	0.078	-10000	0	-0.36	26	26
BAX	0.027	0.004	-10000	0	-10000	0	0
FOXO3	-0.005	0.003	-10000	0	-10000	0	0
FOXO1	0.021	0.019	-10000	0	-0.36	1	1
FOXO4	0.015	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.026	0.006	-10000	0	-10000	0	0
TAT	-0.13	0.18	-10000	0	-0.36	224	224
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.025	0.049	-10000	0	-0.26	26	26
PPARGC1A	-0.026	0.13	-10000	0	-0.36	84	84
FHL2	0.028	0.001	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.037	0.011	-10000	0	-10000	0	0
HIST2H4A	0.007	0.039	0.27	1	-0.31	8	9
SIRT1/FOXO3a	0.019	0.02	-10000	0	-10000	0	0
SIRT1	0.024	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.052	0.013	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.015	0.047	-10000	0	-0.22	4	4
apoptosis	-0.05	0.016	-10000	0	-10000	0	0
SIRT1/PGC1A	0.001	0.084	-10000	0	-0.21	83	83
p53/SIRT1	0.027	0.019	0.37	1	-10000	0	1
SIRT1/FOXO4	0.023	0.031	-10000	0	-0.2	2	2
FOXO1/FHL2/SIRT1	0.039	0.025	-10000	0	-0.19	1	1
HIST1H1E	0.006	0.039	0.2	2	-0.25	4	6
SIRT1/p300	0.037	0.011	-10000	0	-10000	0	0
muscle cell differentiation	-0.02	0.052	0.22	25	-0.22	3	28
TP53	0.02	0.012	0.19	1	-10000	0	1
KU70/SIRT1/BAX	0.05	0.016	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
MEF2D	0.027	0.004	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.07	0.14	-10000	0	-0.25	222	222
ACSS2	0.007	0.013	-10000	0	-0.25	1	1
SIRT1/PCAF/MYOD	0.02	0.052	0.22	3	-0.22	25	28

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.041	0.02	0.26	2	-0.25	1	3
PDGFRB	0.023	0.05	-10000	0	-0.44	7	7
SPHK1	-0.005	0.068	-10000	0	-0.64	6	6
mol:S1P	-0.007	0.061	-10000	0	-0.54	6	6
S1P1/S1P/Gi	-0.059	0.16	-10000	0	-0.43	47	47
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
PDGFB-D/PDGFRB/PLCgamma1	-0.005	0.17	0.29	15	-0.43	30	45
PLCG1	-0.056	0.13	0.28	5	-0.45	31	36
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.05	-10000	0	-0.44	7	7
GNAI2	0.028	0.008	-10000	0	-10000	0	0
GNAI3	0.027	0.008	-10000	0	-10000	0	0
GNAI1	0.014	0.068	-10000	0	-0.36	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.006	0.016	0.19	2	-0.2	1	3
S1P1/S1P	0.021	0.065	0.22	4	-0.38	4	8
negative regulation of cAMP metabolic process	-0.058	0.16	-10000	0	-0.42	48	48
MAPK3	-0.064	0.17	0.26	2	-0.55	33	35
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
KDR	0.027	0.017	-10000	0	-0.36	1	1
PLCB2	0.022	0.069	0.25	12	-0.34	4	16
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	0.017	0.053	-10000	0	-0.32	4	4
receptor internalization	0.019	0.061	0.2	4	-0.33	5	9
PTGS2	-0.059	0.2	0.38	2	-0.8	23	25
Rac1/GTP	0.015	0.051	-10000	0	-0.34	3	3
RHOA	0.027	0.004	-10000	0	-10000	0	0
VEGFA	0.029	0.019	0.36	2	-10000	0	2
negative regulation of T cell proliferation	-0.058	0.16	-10000	0	-0.42	48	48
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.036	-10000	0	-0.37	5	5
MAPK1	-0.06	0.16	-10000	0	-0.51	37	37
S1P1/S1P/PDGFB-D/PDGFRB	0.044	0.09	0.28	15	-0.32	4	19
ABCC1	0.028	0.004	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.001	0.035	0.2	17	-10000	0	17
RFC1	0	0.029	0.18	15	-10000	0	15
PRKDC	0.015	0.065	0.22	51	-10000	0	51
RIPK1	0.028	0.004	-10000	0	-10000	0	0
CASP7	0.006	0.098	-10000	0	-0.54	16	16
FASLG/FAS/FADD/FAF1	0.008	0.063	0.2	16	-0.22	27	43
MAP2K4	-0.015	0.098	0.25	1	-0.36	19	20
mol:ceramide	0.005	0.079	-10000	0	-0.28	31	31
GSN	0	0.039	0.2	17	-0.19	5	22
FASLG/FAS/FADD/FAF1/Caspase 8	0.004	0.072	0.26	1	-0.28	24	25
FAS	0.02	0.045	-10000	0	-0.36	8	8
BID	-0.01	0.05	0.25	21	-0.28	1	22
MAP3K1	0.007	0.081	0.21	6	-0.35	15	21
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
RB1	0.023	0.075	0.22	73	-10000	0	73
CFLAR	0.028	0.002	-10000	0	-10000	0	0
HGF/MET	0.03	0.083	-10000	0	-0.27	40	40
ARHGDIB	0.001	0.036	0.21	15	-10000	0	15
FADD	0.026	0.008	-10000	0	-10000	0	0
actin filament polymerization	0.004	0.047	0.19	5	-0.2	17	22
NFKB1	-0.007	0.12	-10000	0	-0.68	18	18
MAPK8	-0.022	0.11	0.24	1	-0.41	20	21
DFFA	0	0.029	0.18	15	-10000	0	15
DNA fragmentation during apoptosis	-0.003	0.039	0.18	16	-10000	0	16
FAS/FADD/MET	0.044	0.045	0.25	1	-0.24	12	13
CFLAR/RIP1	0.041	0.007	-10000	0	-10000	0	0
FAIM3	0.01	0.081	-10000	0	-0.36	28	28
FAF1	0.022	0.017	-10000	0	-10000	0	0
PARP1	0	0.029	0.18	15	-10000	0	15
DFFB	0.001	0.03	0.18	16	-10000	0	16
CHUK	-0.011	0.12	-10000	0	-0.62	19	19
FASLG	0.001	0.087	-10000	0	-0.36	32	32
FAS/FADD	0.033	0.036	-10000	0	-0.25	8	8
HGF	0.017	0.061	-10000	0	-0.37	15	15
LMNA	-0.003	0.039	0.24	5	-10000	0	5
CASP6	0	0.029	0.18	15	-10000	0	15
CASP10	0.027	0.007	-10000	0	-10000	0	0
CASP3	0.003	0.035	0.22	15	-10000	0	15
PTPN13	0.007	0.094	-10000	0	-0.43	27	27
CASP8	-0.006	0.068	0.31	27	-10000	0	27
IL6	-0.03	0.19	-10000	0	-0.93	17	17
MET	0.023	0.045	0.36	1	-0.44	5	6
ICAD/CAD	-0.001	0.027	0.24	2	-10000	0	2
FASLG/FAS/FADD/FAF1/Caspase 10	0.005	0.08	-10000	0	-0.28	31	31
activation of caspase activity by cytochrome c	-0.01	0.05	0.25	21	-0.28	1	22
PAK2	0.001	0.032	0.18	17	-10000	0	17
BCL2	0.014	0.05	-10000	0	-0.36	10	10

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.036	0.008	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.027	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.031	-10000	0	-0.36	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.023	0.011	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.014	0.011	-10000	0	-0.17	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.022	0.019	-10000	0	-0.36	1	1
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
FYN	0.027	0.005	-10000	0	-10000	0	0
MAP3K12	0.028	0.002	-10000	0	-10000	0	0
FGR	0.023	0.034	-10000	0	-0.38	4	4
p38 alpha/TAB1	-0.06	0.11	-10000	0	-0.31	74	74
PRKG1	0.013	0.071	-10000	0	-0.36	21	21
DUSP8	0.026	0.022	-10000	0	-0.36	2	2
PGK/cGMP/p38 alpha	-0.026	0.14	0.16	14	-0.34	59	73
apoptosis	-0.058	0.1	-10000	0	-0.3	74	74
RAL/GTP	0.034	0.011	-10000	0	-10000	0	0
LYN	0.024	0.009	-10000	0	-10000	0	0
DUSP1	0.025	0.027	-10000	0	-0.36	3	3
PAK1	0.027	0.004	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.054	0.032	-10000	0	-10000	0	0
TRAF6	0.027	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.025	0.017	-10000	0	-0.36	1	1
RAC1-CDC42/GTP	0.032	0.017	-10000	0	-0.21	1	1
MAPK11	-0.009	0.14	0.22	45	-0.35	31	76
BLK	-0.09	0.17	-10000	0	-0.36	172	172
HCK	0.011	0.047	-10000	0	-0.36	9	9
MAP2K3	0.024	0.01	-10000	0	-10000	0	0
DUSP16	0.027	0.005	-10000	0	-10000	0	0
DUSP10	0.025	0.036	0.36	1	-0.44	3	4
TRAF6/MEKK3	0.034	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.02	0.15	0.21	40	-0.34	70	110
positive regulation of innate immune response	-0.02	0.17	0.25	41	-0.41	47	88
LCK	0.019	0.058	-10000	0	-0.43	10	10
p38alpha-beta/MKP7	-0.013	0.16	0.25	38	-0.4	43	81
p38alpha-beta/MKP5	-0.012	0.16	0.25	40	-0.4	44	84
PGK/cGMP	0.01	0.049	-10000	0	-0.25	21	21
PAK2	0.028	0.002	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.013	0.16	0.25	40	-0.41	42	82
CDC42	0.025	0.017	-10000	0	-0.36	1	1
RALB	0.028	0.001	-10000	0	-10000	0	0
RALA	0.025	0.008	-10000	0	-10000	0	0
PAK3	0.01	0.022	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.023	0.046	-10000	0	-0.44	6	6
GPC2	0.013	0.081	0.36	1	-0.44	18	19
GPC2/Midkine	0.025	0.07	0.26	1	-0.32	24	25
neuron projection morphogenesis	0.025	0.07	0.26	1	-0.32	24	25

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.01	0.046	-10000	0	-0.35	1	1
STMN1	0.013	0.013	-10000	0	-0.25	1	1
Aurora B/RasGAP/Survivin	0.052	0.03	0.25	1	-0.26	1	2
Chromosomal passenger complex/Cul3 protein complex	-0.012	0.082	0.15	1	-0.27	25	26
BIRC5	0.03	0.023	0.35	1	-0.44	1	2
DES	-0.41	0.3	-10000	0	-0.58	437	437
Aurora C/Aurora B/INCENP	0.048	0.032	-10000	0	-0.19	4	4
Aurora B/TACC1	0.031	0.018	-10000	0	-10000	0	0
Aurora B/PP2A	0.037	0.018	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.009	0.005	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.004	-10000	0	-10000	0	0
NDC80	0.013	0.008	-10000	0	-10000	0	0
Cul3 protein complex	0.018	0.092	-10000	0	-0.21	83	83
KIF2C	0.015	0.049	-10000	0	-0.35	8	8
PEBP1	0.029	0.003	-10000	0	-10000	0	0
KIF20A	0.029	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.038	0.018	-10000	0	-10000	0	0
SEPT1	0.023	0.041	-10000	0	-0.36	7	7
SMC2	0.027	0.016	-10000	0	-0.36	1	1
SMC4	0.026	0.022	-10000	0	-0.36	2	2
NSUN2/NPM1/Nucleolin	-0.072	0.2	-10000	0	-0.5	106	106
PSMA3	0.026	0.007	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	0.015	0.007	-10000	0	-10000	0	0
AURKB	0.028	0.014	-10000	0	-10000	0	0
AURKC	0.023	0.033	-10000	0	-0.36	4	4
CDCA8	0.03	0.005	-10000	0	-10000	0	0
cytokinesis	0.005	0.039	-10000	0	-0.37	3	3
Aurora B/Septin1	0.005	0.11	-10000	0	-0.3	15	15
AURKA	0.017	0.014	-10000	0	-10000	0	0
INCENP	0.03	0.005	-10000	0	-10000	0	0
KLHL13	-0.026	0.13	-10000	0	-0.36	84	84
BUB1	0.03	0.004	-10000	0	-10000	0	0
hSgo1/Aurora B/Survivin	0.05	0.033	0.24	1	-0.24	3	4
EVI5	0.028	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.049	0.065	-10000	0	-0.29	1	1
SGOL1	0.026	0.027	-10000	0	-0.44	2	2
CENPA	0.033	0.059	0.14	1	-0.19	11	12
NCAPG	0.027	0.005	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.038	0.018	-10000	0	-10000	0	0
NCAPD2	0.027	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.038	0.018	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
NCAPH	0.028	0	-10000	0	-10000	0	0
NPM1	-0.042	0.15	-10000	0	-0.33	101	101
RASA1	0.027	0.005	-10000	0	-10000	0	0
KLHL9	0.027	0.005	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.018	-10000	0	-10000	0	0
PPP1CC	0.028	0.002	-10000	0	-10000	0	0
Centraspindlin	0.044	0.065	-10000	0	-0.26	3	3
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
NSUN2	-0.032	0.11	-10000	0	-0.28	98	98
MYLK	-0.023	0.092	-10000	0	-0.26	83	83
KIF23	0.027	0.02	-10000	0	-0.44	1	1
VIM	0.014	0.008	-10000	0	-10000	0	0
RACGAP1	0.028	0.004	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.032	0.11	-10000	0	-0.28	99	99
Chromosomal passenger complex	0.02	0.052	0.17	1	-0.18	15	16
Chromosomal passenger complex/EVI5	0.095	0.057	0.3	1	-0.22	1	2
TACC1	0.024	0.01	-10000	0	-10000	0	0
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
CUL3	0.028	0.001	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.007	0.047	-10000	0	-0.36	2	2
SVIL	0.011	0.04	-10000	0	-0.36	1	1
ZNF318	0.05	0.057	0.19	41	-10000	0	41
JMJD2C	0.004	0.021	0.048	2	-0.073	29	31
T-DHT/AR/Ubc9	0.019	0.069	-10000	0	-0.21	47	47
CARM1	0.02	0.019	-10000	0	-10000	0	0
PRDX1	0.029	0.006	-10000	0	-10000	0	0
PELP1	0.026	0.015	-10000	0	-10000	0	0
CTNNB1	0.013	0.034	-10000	0	-10000	0	0
AKT1	0.032	0.019	-10000	0	-10000	0	0
PTK2B	0.011	0.034	-10000	0	-0.36	2	2
MED1	0.036	0.029	0.38	2	-10000	0	2
MAK	0.033	0.1	0.19	57	-0.43	21	78
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	0.011	0.039	-10000	0	-0.36	1	1
GSN	0.001	0.07	-10000	0	-0.38	13	13
NCOA2	0.017	0.032	-10000	0	-0.36	3	3
NCOA6	0.009	0.028	-10000	0	-10000	0	0
DNA-PK	0.064	0.055	0.22	6	-10000	0	6
NCOA4	0.024	0.019	-10000	0	-0.36	1	1
PIAS3	0.012	0.034	-10000	0	-10000	0	0
cell proliferation	0.028	0.071	0.25	3	-0.38	5	8
XRCC5	0.033	0.013	-10000	0	-10000	0	0
UBE3A	0.007	0.05	-10000	0	-0.36	1	1
T-DHT/AR/SNURF	-0.007	0.1	-10000	0	-0.23	98	98
FHL2	0.042	0.053	-10000	0	-10000	0	0
RANBP9	0.009	0.044	-10000	0	-0.36	1	1
JMJD1A	0.002	0.012	-10000	0	-0.12	4	4
CDK6	0.027	0.007	-10000	0	-10000	0	0
TGFB1I1	0.012	0.037	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.005	0.077	0.18	1	-0.22	51	52
XRCC6	0.032	0.015	-10000	0	-10000	0	0
T-DHT/AR	0.027	0.076	-10000	0	-0.2	43	43
CTDSP1	0.018	0.024	-10000	0	-10000	0	0
CTDSP2	0.043	0.038	-10000	0	-10000	0	0
BRCA1	0.012	0.036	-10000	0	-10000	0	0
TCF4	0.026	0.035	-10000	0	-0.36	2	2
CDKN2A	-0.053	0.19	0.38	2	-0.44	115	117
SRF	0.04	0.021	-10000	0	-10000	0	0
NKX3-1	-0.004	0.033	-10000	0	-0.17	6	6
KLK3	-0.19	0.48	-10000	0	-1.3	99	99
TMF1	0.019	0.024	-10000	0	-0.36	1	1
HNRNPA1	0.037	0.022	-10000	0	-10000	0	0
AOF2	-0.012	0.029	-10000	0	-0.078	99	99
APPL1	0.025	0.041	0.15	2	-0.25	3	5
T-DHT/AR/Caspase 8	0.029	0.074	-10000	0	-0.2	47	47
AR	-0.004	0.1	-10000	0	-0.36	47	47
UBA3	0.017	0.023	-10000	0	-10000	0	0
PATZ1	0.035	0.022	-10000	0	-10000	0	0
PAWR	0.02	0.019	-10000	0	-10000	0	0
PRKDC	0.029	0.02	0.36	1	-10000	0	1
PA2G4	0.038	0.025	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.026	0.065	-10000	0	-0.18	46	46
RPS6KA3	0.009	0.043	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.014	0.07	-10000	0	-0.21	48	48
LATS2	0.028	0.023	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.032	0.072	0.16	12	-0.18	42	54
Cyclin D3/CDK11 p58	0.022	0.005	-10000	0	-10000	0	0
VAV3	-0.017	0.11	-10000	0	-0.37	49	49
KLK2	-0.002	0.072	-10000	0	-0.3	28	28
CASP8	0.031	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.018	0.072	-10000	0	-0.2	43	43
TMPRSS2	0.004	0.071	-10000	0	-0.69	5	5
CCND1	0.014	0.047	0.35	1	-0.44	4	5
PIAS1	0.007	0.049	-10000	0	-10000	0	0
mol:T-DHT	0.001	0.01	-10000	0	-0.056	6	6
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.002	0.07	-10000	0	-0.16	89	89
T-DHT/AR/CDK6	0.022	0.07	-10000	0	-0.2	45	45
CMTM2	0.011	0.09	-10000	0	-0.44	23	23
SNURF	-0.024	0.12	-10000	0	-0.37	61	61
ZMIZ1	0.027	0.018	-10000	0	-10000	0	0
CCND3	0.028	0.005	-10000	0	-10000	0	0
TGIF1	0.028	0.023	-10000	0	-10000	0	0
FKBP4	0.01	0.044	0.36	1	-10000	0	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.027	0.067	0.3	23	-0.24	2	25
KIRREL	0.021	0.048	-10000	0	-0.38	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.027	0.067	0.24	2	-0.3	23	25
PLCG1	0.016	0.014	-10000	0	-10000	0	0
ARRB2	0.023	0.01	-10000	0	-10000	0	0
WASL	0.027	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.043	0.079	0.23	2	-0.23	42	44
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.02	0.037	0.2	2	-0.22	7	9
FYN	0.01	0.062	0.28	12	-0.21	25	37
mol:Ca2+	0.027	0.061	0.22	1	-0.24	21	22
mol:DAG	0.027	0.062	0.22	1	-0.24	21	22
NPHS2	0.013	0.049	-10000	0	-0.45	6	6
mol:IP3	0.027	0.062	0.22	1	-0.24	21	22
regulation of endocytosis	0.036	0.054	0.21	2	-0.2	18	20
Nephrin/NEPH1/podocin/Cholesterol	0.035	0.059	0.21	2	-0.23	25	27
establishment of cell polarity	0.027	0.067	0.24	2	-0.3	23	25
Nephrin/NEPH1/podocin/NCK1-2	0.064	0.063	-10000	0	-0.24	11	11
Nephrin/NEPH1/beta Arrestin2	0.037	0.056	0.22	2	-0.2	18	20
NPHS1	0.013	0.076	0.32	2	-0.44	15	17
Nephrin/NEPH1/podocin	0.037	0.054	0.21	2	-0.21	25	27
TJP1	0.026	0.007	-10000	0	-10000	0	0
NCK1	0.028	0.002	-10000	0	-10000	0	0
NCK2	0.028	0.001	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.028	0.062	0.23	1	-0.24	21	22
CD2AP	0.016	0.066	-10000	0	-0.36	18	18
Nephrin/NEPH1/podocin/GRB2	0.05	0.064	0.23	2	-0.24	25	27
GRB2	0.027	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.011	0.076	0.3	12	-0.21	43	55
cytoskeleton organization	0.009	0.046	0.2	7	-0.35	2	9
Nephrin/NEPH1	0.025	0.047	0.19	2	-0.21	22	24
Nephrin/NEPH1/ZO-1	0.04	0.058	0.22	2	-0.24	20	22

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.007	0.048	0.29	1	-10000	0	1
DAPP1	-0.012	0.14	0.18	75	-0.38	34	109
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.06	0.18	0.24	13	-0.5	52	65
mol:DAG	0	0.093	0.18	71	-0.23	17	88
HRAS	0.027	0.017	-10000	0	-0.36	1	1
RAP1A	0.027	0.007	-10000	0	-10000	0	0
ARF5/GDP	0.027	0.12	0.2	4	-0.39	22	26
PLCG2	-0.004	0.1	-10000	0	-0.36	49	49
PLCG1	0.016	0.014	-10000	0	-10000	0	0
ARF5	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	-0.014	0.031	0.3	1	-10000	0	1
ARF1/GTP	0.002	0.04	0.25	3	-10000	0	3
RHOA	0.027	0.004	-10000	0	-10000	0	0
YES1	0.022	0.019	-10000	0	-0.36	1	1
RAP1A/GTP	-0.014	0.03	0.16	14	-10000	0	14
ADAP1	-0.015	0.03	0.28	1	-0.33	1	2
ARAP3	-0.013	0.031	0.3	1	-10000	0	1
INPPL1	0.027	0.004	-10000	0	-10000	0	0
PREX1	0.015	0.025	-10000	0	-0.36	2	2
ARHGEF6	0.019	0.056	-10000	0	-0.36	13	13
ARHGEF7	0.022	0.012	-10000	0	-10000	0	0
ARF1	0.027	0.004	-10000	0	-10000	0	0
NRAS	0.026	0.023	-10000	0	-0.36	2	2
FYN	0.027	0.005	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
FGR	0.023	0.034	-10000	0	-0.38	4	4
mol:Ca2+	0.004	0.057	0.16	19	-10000	0	19
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.011	0.11	-10000	0	-0.36	59	59
ZAP70	0.018	0.06	-10000	0	-0.37	14	14
mol:IP3	-0.002	0.07	0.14	71	-0.18	8	79
LYN	0.024	0.009	-10000	0	-10000	0	0
ARF1/GDP	0.028	0.12	0.2	6	-0.4	23	29
RhoA/GDP	0.04	0.069	0.25	5	-0.29	3	8
PDK1/Src/Hsp90	0.032	0.028	-10000	0	-10000	0	0
BLNK	0.022	0.041	-10000	0	-0.36	7	7
actin cytoskeleton reorganization	0.035	0.092	0.23	35	-0.34	8	43
SRC	0.017	0.014	-10000	0	-10000	0	0
PLEKHA2	-0.008	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PTEN	0.026	0.01	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
ARF6/GTP	-0.014	0.035	0.29	1	-10000	0	1
RhoA/GTP	-0.014	0.033	0.3	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.032	0.099	-10000	0	-0.35	29	29
BLK	-0.09	0.17	-10000	0	-0.36	172	172
PDPK1	0.027	0.004	-10000	0	-10000	0	0
CYTH1	-0.015	0.029	0.28	1	-10000	0	1
HCK	0.011	0.047	-10000	0	-0.36	9	9
CYTH3	-0.015	0.028	0.28	1	-10000	0	1
CYTH2	-0.015	0.029	0.28	1	-10000	0	1
KRAS	0.027	0.017	-10000	0	-0.36	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.013	0.079	-10000	0	-0.36	22	22
SGK1	-0.003	0.082	-10000	0	-0.37	26	26
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
mol:GDP	0.017	0.12	0.18	9	-0.32	40	49
SOS1	0.028	0.002	-10000	0	-10000	0	0
SYK	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.026	0.066	0.24	9	-0.29	3	12
mol:PI-3-4-5-P3	-0.014	0.03	0.28	1	-10000	0	1
ARAP3/RAP1A/GTP	-0.014	0.03	0.16	14	-10000	0	14
VAV1	0.011	0.077	-10000	0	-0.36	25	25
mol:PI-3-4-P2	0.013	0.011	-10000	0	-0.25	1	1
RAS family/GTP/PI3K Class I	0.044	0.039	-10000	0	-10000	0	0
PLEKHA1	-0.009	0.008	-10000	0	-0.21	1	1
Rac1/GDP	0.022	0.11	0.2	4	-0.4	21	25
LAT	0.025	0.035	-10000	0	-0.4	4	4
Rac1/GTP	-0.016	0.1	-10000	0	-0.34	42	42
ITK	-0.022	0.041	0.28	1	-10000	0	1
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.009	0.11	0.2	65	-0.31	23	88
LCK	0.019	0.058	-10000	0	-0.43	10	10
BTK	-0.032	0.056	0.28	1	-10000	0	1

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.007	0.013	-10000	0	-0.2	2	2
RAS family/GTP	0.011	0.088	0.23	1	-0.26	9	10
NFATC4	-0.022	0.055	0.25	2	-10000	0	2
ERBB2IP	0.023	0.041	-10000	0	-0.36	7	7
HSP90 (dimer)	0.026	0.007	-10000	0	-10000	0	0
mammary gland morphogenesis	0.003	0.068	0.19	1	-10000	0	1
JUN	0.005	0.067	0.21	3	-0.23	3	6
HRAS	0.027	0.016	-10000	0	-0.36	1	1
DOCK7	-0.026	0.061	0.16	1	-10000	0	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.02	0.074	0.22	4	-0.2	9	13
AKT1	0.004	0.006	-10000	0	-10000	0	0
BAD	-0.006	0.009	-10000	0	-0.21	1	1
MAPK10	-0.02	0.064	0.21	4	-0.22	12	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.006	0.074	0.21	1	-10000	0	1
RAF1	-0.005	0.087	0.28	5	-0.29	8	13
ErbB2/ErbB3/neuregulin 2	-0.002	0.084	0.2	12	-0.2	76	88
STAT3	0.017	0.06	-10000	0	-0.79	3	3
cell migration	-0.013	0.066	0.21	10	-0.2	11	21
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	-0.042	0.22	0.37	2	-0.58	71	73
FOS	-0.017	0.14	0.33	2	-0.35	74	76
NRAS	0.026	0.023	-10000	0	-0.36	2	2
mol:Ca2+	0.003	0.068	0.19	1	-10000	0	1
MAPK3	-0.024	0.17	0.31	4	-0.48	57	61
MAPK1	-0.039	0.19	0.36	2	-0.52	66	68
JAK2	-0.027	0.062	0.16	1	-10000	0	1
NF2	0.004	0.06	-10000	0	-0.59	6	6
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.003	0.067	0.18	2	-0.21	52	54
NRG1	-0.015	0.11	-10000	0	-0.36	56	56
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
MAPK8	-0.018	0.089	0.17	1	-0.24	45	46
MAPK9	-0.008	0.052	0.2	5	-10000	0	5
ERBB2	-0.012	0.05	0.27	18	-10000	0	18
ERBB3	0.027	0.003	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
apoptosis	0.005	0.011	0.2	1	-10000	0	1
STAT3 (dimer)	0.017	0.059	-10000	0	-0.78	3	3
RNF41	-0.009	0.012	-10000	0	-10000	0	0
FRAP1	-0.003	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.01	0.047	-10000	0	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	0.012	0.039	0.21	18	-10000	0	18
CHRNA1	-0.032	0.2	0.29	4	-0.59	58	62
myelination	-0.018	0.062	0.27	5	-10000	0	5
PPP3CB	-0.025	0.058	0.16	1	-10000	0	1
KRAS	0.026	0.016	-10000	0	-0.36	1	1
RAC1-CDC42/GDP	0.009	0.077	-10000	0	-10000	0	0
NRG2	-0.04	0.13	-10000	0	-0.36	88	88
mol:GDP	-0.003	0.067	0.18	2	-0.21	52	54
SOS1	0.028	0.002	-10000	0	-10000	0	0
MAP2K2	-0.013	0.09	0.28	4	-0.32	11	15
SRC	0.017	0.014	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.027	0.062	0.16	1	-10000	0	1
MAP2K1	-0.046	0.2	0.36	1	-0.56	54	55
heart morphogenesis	0.003	0.068	0.19	1	-10000	0	1
RAS family/GDP	0.015	0.089	0.25	1	-0.28	1	2
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.007	0.063	-10000	0	-0.62	6	6
CHRNE	0.005	0.025	0.077	1	-0.14	11	12
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
activation of caspase activity	-0.004	0.006	-10000	0	-10000	0	0
nervous system development	0.003	0.068	0.19	1	-10000	0	1
CDC42	0.025	0.017	-10000	0	-0.36	1	1

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.026	0.023	-10000	0	-10000	0	0
HSPA8	0.026	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0	0.1	-10000	0	-0.29	35	35
AKT1	-0.008	0.054	-10000	0	-10000	0	0
GSC	-0.038	0.13	-10000	0	-0.55	6	6
NKX2-5	-0.001	0.011	-10000	0	-10000	0	0
muscle cell differentiation	0.041	0.12	0.37	18	-10000	0	18
SMAD2-3/SMAD4/SP1	-0.01	0.11	-10000	0	-0.29	3	3
SMAD4	0.001	0.047	-10000	0	-10000	0	0
CBFB	0.028	0.003	-10000	0	-10000	0	0
SAP18	0.021	0.011	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.018	0.14	-10000	0	-0.27	137	137
SMAD3/SMAD4/VDR	0.057	0.06	-10000	0	-10000	0	0
MYC	0.048	0.06	0.36	9	-0.38	2	11
CDKN2B	-0.44	0.62	-10000	0	-1.3	217	217
AP1	0.013	0.053	-10000	0	-0.3	1	1
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.019	0.12	-10000	0	-0.35	43	43
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.15	0.22	-10000	0	-0.42	206	206
SP3	0.029	0.001	-10000	0	-10000	0	0
CREB1	0.028	0	-10000	0	-10000	0	0
FOXH1	0.009	0.07	0.36	3	-0.38	15	18
SMAD3/SMAD4/GR	0.01	0.1	-10000	0	-0.28	37	37
GATA3	0.017	0.051	-10000	0	-0.39	5	5
SKI/SIN3/HDAC complex/NCoR1	0.022	0.062	-10000	0	-0.44	4	4
MEF2C/TIF2	0	0.087	-10000	0	-0.36	15	15
endothelial cell migration	0.025	0.12	0.54	1	-10000	0	1
MAX	0.03	0.012	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
RBBP4	0.026	0.005	-10000	0	-10000	0	0
RUNX2	0.027	0.004	-10000	0	-10000	0	0
RUNX3	0.025	0.017	-10000	0	-0.36	1	1
RUNX1	0.026	0.007	-10000	0	-10000	0	0
CTBP1	0.027	0.005	-10000	0	-10000	0	0
NR3C1	0.003	0.1	-10000	0	-0.36	44	44
VDR	0.028	0.002	-10000	0	-10000	0	0
CDKN1A	-0.009	0.081	-10000	0	-0.88	2	2
KAT2B	0.012	0.077	-10000	0	-0.35	26	26
SMAD2/SMAD2/SMAD4/FOXH1	-0.001	0.078	0.27	2	-0.27	11	13
DCP1A	0.027	0.004	-10000	0	-10000	0	0
SKI	0.026	0.006	-10000	0	-10000	0	0
SERPINE1	-0.025	0.12	-10000	0	-0.54	1	1
SMAD3/SMAD4/ATF2	0.018	0.064	-10000	0	-0.27	1	1
SMAD3/SMAD4/ATF3	0.018	0.065	-10000	0	-0.3	2	2
SAP30	0.026	0.006	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.054	0.048	-10000	0	-10000	0	0
JUN	0.003	0.045	-10000	0	-0.3	1	1
SMAD3/SMAD4/IRF7	0.018	0.064	-10000	0	-10000	0	0
TFE3	0.018	0.025	-10000	0	-10000	0	0
COL1A2	0.002	0.083	-10000	0	-0.3	40	40
mesenchymal cell differentiation	-0.018	0.063	-10000	0	-10000	0	0
DLX1	0.002	0.081	-10000	0	-0.43	19	19
TCF3	0.027	0.004	-10000	0	-10000	0	0
FOS	0.02	0.042	-10000	0	-0.37	6	6
SMAD3/SMAD4/Max	0.026	0.069	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.055	0.019	-10000	0	-10000	0	0
ZBTB17	0.044	0.036	-10000	0	-0.36	1	1
LAMC1	-0.003	0.041	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.015	0.052	0.28	2	-10000	0	2
IRF7	0.027	0.016	-10000	0	-0.36	1	1
ESR1	-0.01	0.11	-10000	0	-0.36	55	55
HNF4A	0.015	0.02	-10000	0	-0.36	1	1
MEF2C	-0.003	0.093	-10000	0	-0.39	14	14
SMAD2-3/SMAD4	-0.003	0.089	-10000	0	-0.28	3	3
Cbp/p300/Src-1	0.058	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	0.01	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.02	0.036	0.36	6	-10000	0	6
CREBBP	0.027	0.017	-10000	0	-10000	0	0
SKIL	0.027	0.016	-10000	0	-0.36	1	1
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
SNIP1	0.026	0.006	-10000	0	-10000	0	0
GCN5L2	0.004	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.015	0.061	-10000	0	-10000	0	0
MSG1/HSC70	-0.043	0.15	-10000	0	-0.32	138	138
SMAD2	-0.009	0.049	-10000	0	-0.21	1	1
SMAD3	0.002	0.05	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.004	0.048	0.21	6	-0.24	4	10
SMAD2/SMAD2/SMAD4	-0.059	0.12	-10000	0	-0.4	44	44
NCOR1	0.023	0.011	-10000	0	-10000	0	0
NCOA2	0.022	0.028	-10000	0	-0.36	3	3
NCOA1	0.028	0	-10000	0	-10000	0	0
MYOD/E2A	0.033	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.001	0.12	-10000	0	-0.32	1	1
IFNB1	-0.007	0.043	0.2	1	-10000	0	1
SMAD3/SMAD4/MEF2C	0.003	0.11	-10000	0	-0.4	13	13
CITED1	-0.08	0.2	-10000	0	-0.44	138	138
SMAD2-3/SMAD4/ARC105	0.008	0.089	-10000	0	-10000	0	0
RBL1	0.017	0.014	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.15	0.27	-10000	0	-0.52	189	189
RUNX1-3/PEBPB2	0.049	0.021	-10000	0	-0.21	1	1
SMAD7	-0.005	0.087	-10000	0	-0.47	3	3
MYC/MIZ-1	0.068	0.075	0.23	16	-0.29	2	18
SMAD3/SMAD4	-0.001	0.11	0.25	12	-0.34	9	21
IL10	-0.019	0.11	-10000	0	-0.41	38	38
PIASy/HDAC complex	0.013	0.025	-10000	0	-10000	0	0
PIAS3	0.028	0.007	-10000	0	-10000	0	0
CDK2	0.029	0.012	-10000	0	-10000	0	0
IL5	-0.013	0.074	-10000	0	-0.38	7	7
CDK4	0.026	0.027	-10000	0	-0.43	1	1
PIAS4	0.013	0.025	-10000	0	-10000	0	0
ATF3	0.026	0.027	-10000	0	-0.44	2	2
SMAD3/SMAD4/SP1	0.003	0.082	-10000	0	-10000	0	0
FOXG1	-0.069	0.16	-10000	0	-0.46	82	82
FOXO3	-0.023	0.059	-10000	0	-10000	0	0
FOXO1	-0.016	0.05	-10000	0	-0.32	1	1
FOXO4	-0.022	0.057	-10000	0	-10000	0	0
heart looping	-0.003	0.092	-10000	0	-0.38	14	14
CEBPB	0	0.052	0.33	3	-0.45	4	7
SMAD3/SMAD4/DLX1	0.008	0.08	-10000	0	-0.27	18	18
MYOD1	-0.018	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.012	0.049	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	0.012	0.089	-10000	0	-0.32	6	6
SnoN/SIN3/HDAC complex/NCoR1	0.027	0.016	-10000	0	-0.36	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.035	0.069	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.015	0.083	-10000	0	-10000	0	0
MED15	0.026	0.017	-10000	0	-0.36	1	1
SP1	0.003	0.04	-10000	0	-10000	0	0
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.026	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.001	0.076	0.26	2	-0.26	13	15
ITGB5	-0.01	0.053	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.025	0.053	-10000	0	-0.44	2	2
SMAD3/SMAD4/AR	0	0.094	-10000	0	-0.28	28	28
AR	-0.009	0.1	-10000	0	-0.36	47	47
negative regulation of cell growth	-0.01	0.075	0.22	1	-0.3	17	18
SMAD3/SMAD4/MYOD	0.013	0.063	-10000	0	-10000	0	0
E2F5	0.027	0.051	0.36	9	-0.42	3	12
E2F4	0.028	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.022	0.073	0.27	2	-0.3	1	3
SMAD2-3/SMAD4/FOXO1-3a-4	-0.12	0.23	-10000	0	-0.43	200	200
TFDP1	0.022	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.026	0.064	-10000	0	-0.3	1	1
SMAD3/SMAD4/RUNX2	0.018	0.063	-10000	0	-10000	0	0
TGIF2	0.02	0.036	0.36	6	-10000	0	6
TGIF1	0.022	0.011	-10000	0	-10000	0	0
ATF2	0.027	0.016	-10000	0	-0.36	1	1

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.016	-9999	-0.36	1	1
SPHK1	-0.004	0.12	-9999	-0.44	40	40
GNAI2	0.027	0.004	-9999	-10000	0	0
mol:S1P	0.006	0.034	-9999	-0.23	1	1
GNAO1	-0.12	0.19	-9999	-0.36	225	225
mol:Sphinganine-1-P	-0.009	0.082	-9999	-0.32	41	41
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.044	0.045	-9999	-10000	0	0
GNAI3	0.027	0.005	-9999	-10000	0	0
G12/G13	0.036	0.013	-9999	-10000	0	0
S1PR3	0.026	0.019	-9999	-0.44	1	1
S1PR2	0.027	0.004	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.001	0.031	-9999	-0.2	1	1
S1PR5	0.016	0.073	-9999	-0.44	15	15
S1PR4	0.021	0.049	-9999	-0.36	10	10
GNAI1	0.015	0.067	-9999	-0.36	19	19
S1P/S1P5/G12	0.027	0.061	-9999	-0.27	14	14
S1P/S1P3/Gq	0.023	0.056	-9999	-0.34	10	10
S1P/S1P4/Gi	-0.063	0.13	-9999	-0.36	47	47
GNAQ	0.026	0.022	-9999	-0.36	2	2
GNAZ	0.023	0.035	-9999	-0.36	5	5
GNA14	0.024	0.035	-9999	-0.36	5	5
GNA15	0.023	0.046	-9999	-0.44	6	6
GNA12	0.025	0.008	-9999	-10000	0	0
GNA13	0.027	0.005	-9999	-10000	0	0
GNA11	0.025	0.031	-9999	-0.36	4	4
ABCC1	0.027	0.003	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.021	0.056	-10000	0	-0.43	9	9
ANTXR2	0.026	0.023	-10000	0	-0.36	2	2
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.007	-10000	0	-0.052	11	11
monocyte activation	-0.002	0.09	-10000	0	-0.34	41	41
MAP2K2	0.006	0.078	-10000	0	-0.57	11	11
MAP2K1	-0.004	0.006	-10000	0	-10000	0	0
MAP2K7	-0.004	0.009	-10000	0	-0.18	1	1
MAP2K6	-0.005	0.015	-10000	0	-0.18	4	4
CYAA	-0.009	0.028	-10000	0	-0.21	11	11
MAP2K4	-0.003	0.007	-10000	0	-10000	0	0
IL1B	-0.023	0.064	-10000	0	-0.22	57	57
Channel	0.03	0.035	-10000	0	-0.23	11	11
NLRP1	-0.005	0.016	-10000	0	-0.21	3	3
CALM1	0.026	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.016	0.1	-10000	0	-0.38	44	44
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.007	0.052	11	-10000	0	11
MAPK3	-0.004	0.011	0.14	1	-0.18	1	2
MAPK1	-0.004	0.006	-10000	0	-10000	0	0
PGR	-0.048	0.075	-10000	0	-0.18	156	156
PA/Cellular Receptors	0.031	0.039	-10000	0	-0.25	11	11
apoptosis	-0.002	0.007	-10000	0	-0.052	11	11
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.03	0.032	-10000	0	-0.2	11	11
macrophage activation	-0.003	0.024	0.17	10	-0.17	1	11
TNF	0.024	0.035	-10000	0	-0.36	5	5
VCAM1	-0.001	0.09	-10000	0	-0.34	40	40
platelet activation	-0.016	0.1	-10000	0	-0.38	44	44
MAPKKK cascade	0.002	0.014	0.13	1	-0.075	9	10
IL18	-0.003	0.016	-10000	0	-0.17	3	3
negative regulation of macrophage activation	-0.002	0.007	-10000	0	-0.052	11	11
LEF	-0.002	0.007	-10000	0	-0.052	11	11
CASP1	-0.001	0.011	-10000	0	-0.095	5	5
mol:cAMP	-0.017	0.1	-10000	0	-0.38	44	44
necrosis	-0.002	0.007	-10000	0	-0.052	11	11
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.03	0.033	-10000	0	-0.21	11	11
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.007	0.064	-10000	0	-0.26	30	30
CRKL	0.027	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.006	-10000	0	-10000	0	0
DOCK1	0.026	0.016	-10000	0	-0.36	1	1
ITGA4	0.014	0.072	-10000	0	-0.36	22	22
alpha4/beta7 Integrin/MAdCAM1	-0.063	0.15	-10000	0	-0.39	29	29
EPO	0.005	0.05	0.36	2	-0.44	5	7
alpha4/beta7 Integrin	0.02	0.081	-10000	0	-0.28	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.03	0.055	-10000	0	-0.25	22	22
EPO/EPOR (dimer)	0.033	0.038	0.26	2	-0.32	6	8
lamellipodium assembly	0.006	0.081	-10000	0	-0.38	12	12
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
PI3K	0.039	0.015	-10000	0	-0.25	1	1
ARF6	0.026	0.007	-10000	0	-10000	0	0
JAK2	0.015	0.051	0.17	1	-0.41	3	4
PXN	0.028	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
MADCAM1	-0.15	0.19	-10000	0	-0.36	274	274
cell adhesion	-0.063	0.14	-10000	0	-0.39	29	29
CRKL/CBL	0.039	0.01	-10000	0	-10000	0	0
ITGB1	0.028	0.002	-10000	0	-10000	0	0
SRC	0.002	0.046	0.18	1	-0.36	7	8
ITGB7	0.013	0.074	-10000	0	-0.36	23	23
RAC1	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.04	0.07	-10000	0	-0.28	26	26
p130Cas/Crk/Dock1	0.056	0.076	-10000	0	-0.31	7	7
VCAM1	0.019	0.056	-10000	0	-0.36	13	13
RHOA	0.027	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.06	0.049	-10000	0	-10000	0	0
BCAR1	-0.013	0.042	0.18	1	-0.34	7	8
EPOR	0.027	0.019	-10000	0	-0.44	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.027	0.004	-10000	0	-10000	0	0
GIT1	0.026	0.016	-10000	0	-0.36	1	1
Rac1/GTP	0.006	0.083	-10000	0	-0.4	11	11

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.025	0.016	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.01	0.007	-10000	0	-10000	0	0
mol:DAG	0.015	0.061	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.023	0.017	0.22	1	-10000	0	1
CaM/Ca2+	0.024	0.06	-10000	0	-10000	0	0
HIF1A	0.032	0.009	-10000	0	-10000	0	0
GAB1	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.037	0.076	0.33	2	-10000	0	2
PLCG1	0.015	0.061	-10000	0	-10000	0	0
NOS3	0.081	0.11	0.29	85	-10000	0	85
CBL	0.027	0.004	-10000	0	-10000	0	0
mol:NO	0.083	0.11	0.3	91	-0.4	1	92
FLT1	0.014	0.009	-10000	0	-10000	0	0
PGF	0.011	0.083	-10000	0	-0.44	20	20
VEGFR1 homodimer/NRP2/VEGFR121	0.036	0.032	0.3	2	-10000	0	2
CALM1	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
eNOS/Hsp90	0.093	0.11	0.3	91	-0.37	1	92
endothelial cell proliferation	0.048	0.12	0.33	57	-10000	0	57
mol:Ca2+	0.015	0.061	-10000	0	-10000	0	0
MAPK3	0.002	0.056	-10000	0	-10000	0	0
MAPK1	0.001	0.054	0.17	38	-10000	0	38
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
PLGF homodimer	0.011	0.083	-10000	0	-0.44	20	20
PRKACA	0.027	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.019	0.054	-10000	0	-0.36	12	12
VEGFA homodimer	0.028	0.019	0.36	2	-10000	0	2
VEGFR1 homodimer/VEGFA homodimer	0.026	0.024	0.32	2	-10000	0	2
platelet activating factor biosynthetic process	0.074	0.13	0.34	77	-10000	0	77
PI3K	0.038	0.054	-10000	0	-10000	0	0
PRKCA	0.004	0.059	0.18	42	-10000	0	42
PRKCB	-0.013	0.074	0.18	33	-10000	0	33
VEGFR1 homodimer/PLGF homodimer	0.018	0.049	-10000	0	-0.26	16	16
VEGFA	0.028	0.019	0.36	2	-10000	0	2
VEGFB	0.027	0.004	-10000	0	-10000	0	0
mol:IP3	0.015	0.061	-10000	0	-10000	0	0
RASA1	0.051	0.074	-10000	0	-10000	0	0
NRP2	0.026	0.027	-10000	0	-0.36	3	3
VEGFR1 homodimer	0.014	0.009	-10000	0	-10000	0	0
VEGFB homodimer	0.027	0.004	-10000	0	-10000	0	0
NCK1	0.028	0.002	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.083	0.1	0.29	72	-0.39	1	73
PTPN11	0.028	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.037	0.052	-10000	0	-10000	0	0
mol:L-citrulline	0.083	0.11	0.3	91	-0.4	1	92
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.045	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.037	0.028	0.3	2	-10000	0	2
CD2AP	0.016	0.066	-10000	0	-0.36	18	18
PI3K/GAB1	0.08	0.071	-10000	0	-10000	0	0
PDPK1	0.039	0.081	0.34	2	-10000	0	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.037	0.028	0.3	2	-10000	0	2
mol:NADP	0.083	0.11	0.3	91	-0.4	1	92
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.04	0.044	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.024	0.023	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.046	0.15	-10000	0	-0.36	116	116
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.026	0.027	-10000	0	-0.44	2	2
TCEB1	0.024	0.009	-10000	0	-10000	0	0
HIF1A/p53	0.013	0.058	0.26	1	-0.25	25	26
HIF1A	0.003	0.046	-10000	0	-0.26	17	17
COPS5	0.024	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.066	0.035	-10000	0	-0.23	1	1
FIH (dimer)	0.027	0.006	-10000	0	-10000	0	0
CDKN2A	-0.061	0.19	0.36	2	-0.45	115	117
ARNT/IPAS	-0.014	0.11	-10000	0	-0.25	113	113
HIF1AN	0.027	0.006	-10000	0	-10000	0	0
GNB2L1	0.027	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.011	0.062	-10000	0	-0.26	25	25
CUL2	0.028	0.002	-10000	0	-10000	0	0
OS9	0.028	0.002	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.047	0.024	-10000	0	-0.27	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.016	0.06	0.26	1	-0.26	24	25
PHD1-3/OS9	0.062	0.031	-10000	0	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.031	0.066	-10000	0	-0.29	7	7
VHL	0.027	0.004	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
HIF1A/JAB1	0.011	0.061	0.26	1	-0.26	23	24
EGLN3	0.024	0.028	-10000	0	-0.36	3	3
EGLN2	0.027	0.016	-10000	0	-0.36	1	1
EGLN1	0.027	0.005	-10000	0	-10000	0	0
TP53	0.023	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.029	0.078	-10000	0	-0.51	11	11
ARNT	0.027	0.016	-10000	0	-0.36	1	1
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.026	0.017	-10000	0	-0.36	1	1
HIF1A/p19ARF	-0.029	0.11	0.24	2	-0.29	32	34

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.056	0.05	-10000	0	-0.58	1	1
epithelial cell differentiation	0.049	0.073	-10000	0	-0.62	1	1
ITCH	0.018	0.016	-10000	0	-10000	0	0
WWP1	0.014	0.06	-10000	0	-1.1	1	1
FYN	0.027	0.005	-10000	0	-10000	0	0
EGFR	0.024	0.023	-10000	0	-0.36	2	2
PRL	-0.007	0.066	-10000	0	-0.44	12	12
neuron projection morphogenesis	0.025	0.074	0.28	8	-0.43	1	9
PTPRZ1	-0.12	0.18	-10000	0	-0.36	222	222
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.037	0.074	-10000	0	-0.46	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.012	0.06	-10000	0	-0.51	1	1
ADAM17	0.021	0.016	-10000	0	-10000	0	0
ErbB4/ErbB4	0.015	0.036	-10000	0	-0.63	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.053	0.049	-10000	0	-0.58	1	1
NCOR1	0.023	0.011	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.023	0.067	-10000	0	-0.48	1	1
GRIN2B	-0.052	0.12	0.3	3	-0.36	13	16
ErbB4/ErbB2/betacellulin	0.053	0.049	0.28	1	-0.48	1	2
STAT1	0.027	0.019	-10000	0	-0.44	1	1
HBEGF	0.026	0.027	-10000	0	-0.44	2	2
PRLR	0.017	0.062	-10000	0	-0.36	16	16
E4ICDs/ETO2	0.037	0.077	-10000	0	-0.58	1	1
axon guidance	0.046	0.084	0.3	9	-0.72	1	10
NEDD4	0.019	0.015	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.021	0.068	-10000	0	-0.29	27	27
CBFA2T3	-0.022	0.13	-10000	0	-0.36	77	77
ErbB4/ErbB2/HBEGF	0.055	0.047	0.28	1	-0.48	1	2
MAPK3	0.023	0.071	0.26	6	-0.44	1	7
STAT1 (dimer)	0.057	0.049	-10000	0	-0.57	1	1
MAPK1	0.023	0.07	0.26	7	-0.44	1	8
JAK2	0.025	0.028	-10000	0	-0.36	3	3
ErbB4/ErbB2/neuregulin 1 beta	0.012	0.063	0.27	1	-0.48	1	2
NRG1	-0.019	0.076	-10000	0	-0.26	56	56
NRG3	0.005	0.032	-10000	0	-0.4	2	2
NRG2	-0.04	0.13	-10000	0	-0.36	88	88
NRG4	-0.014	0.1	-10000	0	-0.36	50	50
heart development	0.046	0.084	0.3	9	-0.72	1	10
neural crest cell migration	0.012	0.063	0.23	6	-0.48	1	7
ERBB2	0.012	0.038	0.27	11	-10000	0	11
WWOX/E4ICDs	0.053	0.049	-10000	0	-0.58	1	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.042	0.072	-10000	0	-0.55	1	1
apoptosis	-0.039	0.074	0.39	9	-10000	0	9
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.031	0.079	-10000	0	-0.58	1	1
ErbB4/ErbB2/epiregulin	-0.036	0.12	0.3	4	-0.34	5	9
ErbB4/ErbB4/betacellulin/betacellulin	0.054	0.052	-10000	0	-0.58	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.07	0.075	-10000	0	-0.44	2	2
MDM2	0.011	0.032	0.25	1	-0.58	1	2
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.005	0.053	-10000	0	-0.4	1	1
STAT5A	0.05	0.08	0.34	2	-0.69	1	3
ErbB4/EGFR/neuregulin 1 beta	0.02	0.066	-10000	0	-0.48	1	1
DLG4	0.022	0.022	-10000	0	-0.44	1	1
GRB2/SHC	0.039	0.009	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.042	0.043	-10000	0	-0.54	1	1
STAT5A (dimer)	0.075	0.09	0.3	2	-0.68	1	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.08	0.083	0.33	2	-0.69	1	3
LRIG1	0.027	0.016	-10000	0	-0.36	1	1
EREG	-0.16	0.23	0.36	3	-0.44	249	252
BTC	0.021	0.047	-10000	0	-0.36	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.029	0.071	0.36	1	-0.72	1	2
ERBB4	0.011	0.029	-10000	0	-0.64	1	1
STAT5B	0.027	0.004	-10000	0	-10000	0	0
YAP1	0.009	0.06	-10000	0	-0.42	10	10
GRB2	0.027	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.039	0.067	0.28	1	-0.49	1	2
glial cell differentiation	-0.042	0.043	0.54	1	-10000	0	1
WWOX	0.025	0.008	-10000	0	-10000	0	0
cell proliferation	0.023	0.087	0.29	6	-0.52	1	7

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.01	0.021	0.12	7	-0.11	2	9
BUB1B	0.017	0.04	0.12	4	-0.14	5	9
PLK1	0.023	0.028	0.073	55	-0.099	3	58
PLK1S1	0.021	0.049	0.13	4	-0.17	22	26
KIF2A	0.018	0.027	0.18	2	-10000	0	2
regulation of mitotic centrosome separation	0.023	0.028	0.073	55	-0.098	3	58
GOLGA2	0.027	0.004	-10000	0	-10000	0	0
Hec1/SPC24	0.038	0.043	-10000	0	-0.21	10	10
WEE1	0.029	0.038	-10000	0	-0.31	2	2
cytokinesis	0.025	0.036	-10000	0	-10000	0	0
PP2A-alpha B56	0.055	0.083	-10000	0	-0.5	12	12
AURKA	0.025	0.023	0.11	1	-10000	0	1
PICH/PLK1	0.016	0.056	0.18	19	-0.2	5	24
CENPE	0.017	0.027	0.11	1	-0.23	1	2
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.018	0.027	0.18	2	-10000	0	2
PPP2CA	0.027	0.005	-10000	0	-10000	0	0
FZR1	0.027	0.016	-10000	0	-0.36	1	1
TPX2	0.04	0.04	0.11	60	-10000	0	60
PAK1	0.028	0.004	-10000	0	-10000	0	0
SPC24	0.02	0.061	0.36	1	-0.44	10	11
FBXW11	0.027	0.004	-10000	0	-10000	0	0
CLSPN	0.015	0.042	-10000	0	-0.22	17	17
GORASP1	0.027	0.003	-10000	0	-10000	0	0
metaphase	0	0.002	0.017	8	-0.011	1	9
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.011	0.015	0.04	55	-0.052	3	58
G2 phase of mitotic cell cycle	0.001	0.003	0.015	8	-10000	0	8
STAG2	0.027	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.015	0.051	-10000	0	-0.48	6	6
spindle elongation	0.023	0.028	0.073	55	-0.098	3	58
ODF2	0.03	0.005	-10000	0	-10000	0	0
BUB1	0.019	0.08	-10000	0	-0.54	12	12
TPT1	0.026	0.037	0.1	22	-0.17	8	30
CDC25C	0.018	0.04	-10000	0	-0.24	12	12
CDC25B	0.012	0.11	0.35	17	-0.44	27	44
SGOL1	0.01	0.021	0.11	2	-0.12	7	9
RHOA	0.027	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.035	0.056	0.24	17	-10000	0	17
CDC14B	0.007	0.011	-10000	0	-0.25	1	1
CDC20	0.026	0.019	-10000	0	-0.44	1	1
PLK1/PBIP1	0.018	0.021	0.099	2	-10000	0	2
mitosis	-0.002	0.002	-10000	0	-10000	0	0
FBXO5	0.016	0.031	0.15	5	-10000	0	5
CDC2	0.002	0.003	0.015	17	-0.01	1	18
NDC80	0.022	0.011	-10000	0	-10000	0	0
metaphase plate congression	0.007	0.064	-10000	0	-0.22	43	43
ERCC6L	0.017	0.054	0.19	17	-0.21	4	21
NLP/gamma Tubulin	0.012	0.016	0.07	8	-0.086	1	9
microtubule cytoskeleton organization	0.027	0.037	0.1	22	-0.17	8	30
G2/M transition DNA damage checkpoint	0	0.002	0.013	10	-10000	0	10
PPP1R12A	0.027	0.023	-10000	0	-0.36	2	2
interphase	0	0.002	0.013	10	-10000	0	10
PLK1/PRC1-2	0.05	0.027	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.06	0.025	-10000	0	-10000	0	0
RAB1A	0.028	0.001	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.026	0.031	0.064	219	-10000	0	219
mitotic prometaphase	0.001	0.005	0.018	43	-10000	0	43
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.026	-10000	0	-10000	0	0
microtubule-based process	0.035	0.027	0.12	1	-10000	0	1
Golgi organization	0.023	0.028	0.073	55	-0.098	3	58
Cohesin/SA2	0.034	0.023	0.12	1	-10000	0	1
PPP1CB/MYPT1	0.041	0.024	-10000	0	-0.36	2	2
KIF20A	0.027	0.004	-10000	0	-10000	0	0
APC/C/CDC20	0.036	0.029	0.12	1	-0.23	1	2
PPP2R1A	0.027	0.004	-10000	0	-10000	0	0
chromosome segregation	0.017	0.021	0.098	2	-10000	0	2
PRC1	0.027	0.006	-10000	0	-10000	0	0
ECT2	0.017	0.034	0.19	4	-0.2	4	8
C13orf34	0.022	0.026	0.066	71	-10000	0	71
NUDC	0.007	0.065	-10000	0	-0.22	43	43
regulation of attachment of spindle microtubules to kinetochore	0.017	0.04	0.12	4	-0.14	5	9
spindle assembly	0.018	0.024	0.091	12	-0.085	3	15
spindle stabilization	0.021	0.049	0.13	4	-0.17	22	26
APC/C/HCDH1	0.025	0.014	-10000	0	-0.21	2	2
MKLP2/PLK1	0.036	0.027	0.12	1	-10000	0	1
CCNB1	0.027	0.009	-10000	0	-10000	0	0
PPP1CB	0.028	0.016	-10000	0	-0.37	1	1
BTRC	0.027	0.006	-10000	0	-10000	0	0
ROCK2	0.025	0.036	-10000	0	-0.31	3	3
TUBG1	0.018	0.02	0.097	1	-0.16	3	4
G2/M transition of mitotic cell cycle	0.01	0.047	0.18	17	-10000	0	17
MLF1IP	0.007	0.003	-10000	0	-10000	0	0
INCENP	0.028	0.004	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.027	0.004	-10000	0	-10000	0	0
VDR	0.028	0.002	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.041	0.054	-10000	0	-0.21	24	24
EP300	0.026	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0	0.041	-10000	0	-0.29	3	3
KAT2B	0.011	0.078	-10000	0	-0.36	26	26
MAPK14	0.027	0.003	-10000	0	-10000	0	0
AKT1	-0.002	0.05	0.18	2	-0.23	3	5
RAR alpha/9cRA/Cyclin H	0.009	0.072	0.22	1	-0.25	2	3
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.006	0.054	0.2	3	-0.22	13	16
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.004	0.059	-10000	0	-0.22	7	7
NCOR2	0.027	0.016	-10000	0	-0.36	1	1
VDR/VDR/Vit D3	0.02	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.031	0.087	0.4	3	-0.41	8	11
NCOA2	0.022	0.028	-10000	0	-0.36	3	3
NCOA3	0.016	0.014	-10000	0	-10000	0	0
NCOA1	0.028	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.028	0.002	-10000	0	-10000	0	0
RARG	0.028	0.004	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.037	0.005	-10000	0	-10000	0	0
MAPK3	0.027	0.016	-10000	0	-0.36	1	1
MAPK1	0.026	0.006	-10000	0	-10000	0	0
MAPK8	0.028	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.034	0.085	0.26	1	-0.36	10	11
RARA	-0.016	0.061	0.18	4	-0.23	12	16
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.003	0.053	0.2	3	-0.23	14	17
PRKCA	0.028	0.008	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.037	0.091	0.35	3	-0.39	11	14
RXRG	-0.15	0.16	0.3	4	-0.31	253	257
RXRA	-0.013	0.058	0.26	2	-0.21	2	4
RXRB	-0.033	0.089	0.29	5	-0.35	7	12
VDR/Vit D3/DNA	0.02	0.002	-10000	0	-10000	0	0
RBP1	-0.003	0.12	0.36	1	-0.44	40	41
CRBP1/9-cic-RA	-0.001	0.083	0.24	1	-0.31	40	41
RARB	0.026	0.032	-10000	0	-0.36	4	4
PRKCG	-0.13	0.23	0.36	5	-0.44	209	214
MNAT1	0.026	0.007	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.031	0.081	-10000	0	-0.39	11	11
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.023	0.079	0.4	3	-0.36	5	8
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.077	0.27	7	-0.28	5	12
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.036	0.091	0.35	3	-0.39	11	14
positive regulation of DNA binding	0.001	0.063	-10000	0	-0.23	3	3
NRIP1	-0.036	0.1	0.36	1	-0.86	3	4
RXRs/RARs	-0.037	0.091	0.32	3	-0.35	14	17
RXRs/RXRs/DNA/9cRA	-0.043	0.077	-10000	0	-0.37	10	10
PRKACA	0.027	0.003	-10000	0	-10000	0	0
CDK7	0.027	0.005	-10000	0	-10000	0	0
TFIIH	0.051	0.017	-10000	0	-10000	0	0
RAR alpha/9cRA	0.017	0.068	0.23	1	-0.25	2	3
CCNH	0.027	0.004	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.049	0.018	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.063	0.16	0.43	1	-0.84	1	2
CRP	-0.002	0.14	0.43	1	-0.68	4	5
cell cycle arrest	-0.003	0.14	-10000	0	-0.73	4	4
TIMP1	0.007	0.14	-10000	0	-0.6	4	4
IL6ST	0.019	0.061	-10000	0	-0.36	15	15
Rac1/GDP	-0.03	0.12	0.3	1	-0.37	32	33
AP1	0.048	0.09	-10000	0	-0.45	6	6
GAB2	0.028	0.004	-10000	0	-10000	0	0
TNFSF11	0.028	0.17	-10000	0	-0.86	5	5
HSP90B1	0.035	0.049	-10000	0	-10000	0	0
GAB1	0.027	0.005	-10000	0	-10000	0	0
MAPK14	-0.029	0.11	-10000	0	-0.38	19	19
AKT1	0.032	0.037	-10000	0	-0.35	2	2
FOXO1	0.059	0.078	0.23	15	-0.36	1	16
MAP2K6	-0.037	0.11	-10000	0	-0.38	24	24
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.028	0.12	0.29	2	-0.42	16	18
MITF	-0.036	0.12	-10000	0	-0.39	29	29
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.027	0.004	-10000	0	-10000	0	0
A2M	0.008	0.15	-10000	0	-1.1	10	10
CEBPB	0.017	0.047	0.35	3	-0.44	4	7
GRB2/SOS1/GAB family/SHP2	0.025	0.079	0.24	1	-0.38	10	11
STAT3	-0.008	0.14	-10000	0	-0.78	4	4
STAT1	0.021	0.017	-10000	0	-10000	0	0
CEBPD	0.015	0.14	-10000	0	-0.96	2	2
PIK3CA	0.028	0.016	-10000	0	-0.36	1	1
PI3K	0.04	0.015	-10000	0	-0.25	1	1
JUN	0.027	0.004	-10000	0	-10000	0	0
PIAS3/MITF	-0.025	0.12	0.22	1	-0.37	29	30
MAPK11	-0.028	0.11	-10000	0	-0.39	16	16
STAT3 (dimer)/FOXO1	0.04	0.14	0.36	15	-0.62	2	17
GRB2/SOS1/GAB family	0.026	0.13	0.24	3	-0.37	16	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.025	0.1	0.24	3	-0.37	28	31
GRB2	0.027	0.004	-10000	0	-10000	0	0
JAK2	0.025	0.028	-10000	0	-0.36	3	3
LBP	0.054	0.17	0.4	10	-0.6	1	11
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
JAK1	0.028	0.009	-10000	0	-10000	0	0
MYC	0.027	0.15	0.41	1	-0.75	2	3
FGG	-0.016	0.15	-10000	0	-0.65	5	5
macrophage differentiation	-0.003	0.14	-10000	0	-0.73	4	4
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.011	0.14	0.26	4	-0.32	39	43
JUNB	-0.002	0.13	-10000	0	-0.93	3	3
FOS	0.022	0.039	-10000	0	-0.36	6	6
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.033	0.12	0.2	3	-0.37	33	36
STAT1/PIAS1	-0.005	0.11	-10000	0	-0.4	13	13
GRB2/SOS1/GAB family/SHP2/PI3K	0.036	0.039	-10000	0	-0.33	3	3
STAT3 (dimer)	-0.004	0.14	-10000	0	-0.76	4	4
PRKCD	-0.012	0.14	0.32	23	-0.48	9	32
IL6R	-0.052	0.16	-10000	0	-0.36	128	128
SOCS3	-0.025	0.11	0.4	1	-0.52	3	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.052	0.047	-10000	0	-0.21	4	4
Rac1/GTP	-0.029	0.12	-10000	0	-0.42	19	19
HCK	0.011	0.047	-10000	0	-0.36	9	9
MAPKKK cascade	0.038	0.081	-10000	0	-0.48	7	7
bone resorption	0.03	0.17	0.42	1	-0.8	5	6
IRF1	-0.001	0.13	-10000	0	-0.74	2	2
mol:GDP	-0.035	0.12	-10000	0	-0.36	38	38
SOS1	0.028	0.002	-10000	0	-10000	0	0
VAV1	-0.039	0.12	0.19	1	-0.37	38	39
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.059	0.16	0.33	1	-0.5	31	32
PTPN11	0.019	0.048	-10000	0	-0.77	2	2
IL6/IL6RA	-0.054	0.15	0.26	4	-0.29	175	179
gp130 (dimer)/TYK2/TYK2/LMO4	0.05	0.044	-10000	0	-0.21	14	14
gp130 (dimer)/JAK2/JAK2/LMO4	0.047	0.048	-10000	0	-0.21	17	17
IL6	-0.027	0.16	0.36	7	-0.43	77	84
PIAS3	0.027	0.005	-10000	0	-10000	0	0
PTPRE	0.022	0.011	-10000	0	-10000	0	0
PIAS1	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.037	0.11	0.18	3	-0.34	35	38
LMO4	0.029	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.001	0.14	-10000	0	-0.73	4	4
MCL1	0.032	0.045	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.008	0.007	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0.025	-10000	0	-10000	0	0
CDKN1B	0.026	0.067	0.24	4	-0.33	12	16
CDKN1A	0.024	0.069	0.22	2	-0.32	14	16
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.025	0.016	0.36	1	-10000	0	1
FOXO3	0.026	0.059	0.24	1	-0.31	10	11
AKT1	0.003	0.061	0.26	1	-0.32	18	19
BAD	0.027	0.016	-10000	0	-0.36	1	1
AKT3	0.01	0.033	-10000	0	-0.26	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.025	0.067	0.24	1	-0.33	12	13
AKT1/ASK1	0.042	0.091	0.23	3	-0.34	12	15
BAD/YWHAZ	0.046	0.024	-10000	0	-0.21	1	1
RICTOR	0.024	0.035	-10000	0	-0.36	5	5
RAF1	0.027	0.004	-10000	0	-10000	0	0
JNK cascade	-0.039	0.087	0.33	12	-0.22	2	14
TSC1	0.023	0.069	0.24	1	-0.32	14	15
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
AKT1/RAF1	0.046	0.094	0.24	5	-0.34	14	19
EP300	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.027	0.071	0.26	1	-0.31	18	19
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.025	0.067	0.26	2	-0.33	12	14
YWHAQ	0.028	0.002	-10000	0	-10000	0	0
TBC1D4	0.053	0.093	0.24	122	-0.2	1	123
MAP3K5	0.027	0.004	-10000	0	-10000	0	0
MAPKAP1	0.027	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.053	0.093	0.3	10	-0.21	59	69
YWHAH	0.027	0.006	-10000	0	-10000	0	0
AKT1S1	0.026	0.071	0.26	5	-0.33	13	18
CASP9	0.025	0.062	0.24	1	-0.34	10	11
YWHAB	0.016	0.014	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.046	0.094	0.3	8	-0.53	3	11
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.032	0.028	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
AKT2/p21CIP1	0.022	0.075	0.21	2	-0.4	6	8
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.031	-10000	0	-0.27	2	2
CHUK	0.027	0.052	0.24	1	-0.28	8	9
BAD/BCL-XL	0.017	0.065	-10000	0	-0.57	2	2
mTORC2	0.032	0.021	-10000	0	-0.19	5	5
AKT2	0.014	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.064	0.12	0.24	92	-0.41	11	103
PDPK1	0.027	0.004	-10000	0	-10000	0	0
MDM2	0.025	0.069	0.24	3	-0.33	13	16
MAPKKK cascade	-0.046	0.093	0.33	14	-0.24	5	19
MDM2/Cbp/p300	0.052	0.091	0.26	2	-0.51	3	5
TSC1/TSC2	0.023	0.067	0.27	4	-0.32	12	16
proteasomal ubiquitin-dependent protein catabolic process	0.049	0.087	0.25	2	-0.48	3	5
glucose import	0.013	0.093	0.21	83	-10000	0	83
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.048	0.18	6	-0.33	2	8
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.013	0.093	0.21	83	-10000	0	83
GSK3A	0.027	0.07	0.24	7	-0.33	13	20
FOXO1	0.053	0.098	0.24	91	-0.31	10	101
GSK3B	0.025	0.07	0.24	3	-0.32	14	17
SFN	0.025	0.023	-10000	0	-0.36	2	2
G1/S transition of mitotic cell cycle	0.036	0.081	0.27	10	-0.54	3	13
p27Kip1/14-3-3 family	0.048	0.054	0.28	1	-10000	0	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
KPNA1	0.028	0.002	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
YWHAG	0.027	0.006	-10000	0	-10000	0	0
RHEB	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.008	0.004	-10000	0	-10000	0	0
SNTA1	0.016	0.02	-10000	0	-0.36	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.008	0.009	-10000	0	-0.21	1	1
MAPK12	-0.007	0.035	-10000	0	-0.26	11	11
CCND1	0.006	0.039	0.19	1	-0.32	6	7
p38 gamma/SNTA1	0.008	0.041	0.19	5	-0.26	9	14
MAP2K3	0.024	0.01	-10000	0	-10000	0	0
PKN1	0.027	0.003	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.004	0.042	0.2	8	-0.25	11	19
MAP2K6	0.001	0.016	-10000	0	-0.2	4	4
MAPT	-0.058	0.12	0.22	4	-0.27	139	143
MAPK13	0.011	0.005	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.001	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S89. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S89. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.017	0.014	-10000	0	-10000	0	0
NFATC1	-0.021	0.13	0.31	3	-0.38	42	45
NFATC2	0.034	0.053	0.16	6	-0.22	4	10
NFATC3	0.02	0.008	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.054	0.1	0.19	2	-0.27	76	78
Exportin 1/Ran/NUP214	0.055	0.009	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.037	0.12	-10000	0	-0.32	40	40
BCL2/BAX	0.025	0.04	-10000	0	-0.25	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.007	-10000	0	-10000	0	0
BAX	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.028	0.003	-10000	0	-10000	0	0
BAD	0.027	0.016	-10000	0	-0.36	1	1
CABIN1/MEF2D	-0.043	0.1	0.18	1	-0.31	36	37
Calcineurin A alpha-beta B1/BCL2	0.014	0.05	-10000	0	-0.36	10	10
FKBP8	0.027	0.016	-10000	0	-0.36	1	1
activation-induced cell death of T cells	0.043	0.1	0.31	36	-0.18	1	37
KPNB1	0.027	0.004	-10000	0	-10000	0	0
KPNA2	0.028	0.014	0.36	1	-10000	0	1
XPO1	0.028	0	-10000	0	-10000	0	0
SFN	0.025	0.023	-10000	0	-0.36	2	2
MAP3K8	0.028	0.003	-10000	0	-10000	0	0
NFAT4/CK1 alpha	0.028	0.023	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.07	0.067	-10000	0	-0.29	3	3
CABIN1	-0.055	0.1	0.19	1	-0.27	76	77
CALM1	0.026	0.007	-10000	0	-10000	0	0
RAN	0.028	0.003	-10000	0	-10000	0	0
MAP3K1	0.026	0.016	-10000	0	-0.36	1	1
CAMK4	0.006	0.085	-10000	0	-0.36	31	31
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.027	0.016	-10000	0	-0.36	1	1
YWHAH	0.027	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.027	0.057	-10000	0	-0.25	24	24
YWHAB	0.016	0.014	-10000	0	-10000	0	0
MAPK8	0.027	0.004	-10000	0	-10000	0	0
MAPK9	0.027	0.004	-10000	0	-10000	0	0
YWHAG	0.027	0.006	-10000	0	-10000	0	0
FKBP1A	0.023	0.011	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.008	0.13	0.33	2	-0.38	28	30
PRKCH	0.025	0.017	-10000	0	-0.36	1	1
CABIN1/Cbp/p300	0.038	0.013	-10000	0	-10000	0	0
CASP3	0.026	0.007	-10000	0	-10000	0	0
PIM1	0.027	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.007	-10000	0	-10000	0	0
apoptosis	0.01	0.014	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.034	0.045	-10000	0	-0.35	1	1
PRKCB	-0.062	0.16	-10000	0	-0.36	141	141
PRKCE	0.028	0.002	-10000	0	-10000	0	0
JNK2/NFAT4	0.025	0.039	-10000	0	-10000	0	0
BAD/BCL-XL	0.024	0.023	-10000	0	-0.25	1	1
PRKCD	0.027	0.004	-10000	0	-10000	0	0
NUP214	0.027	0.004	-10000	0	-10000	0	0
PRKCZ	0.027	0.006	-10000	0	-10000	0	0
PRKCA	0.027	0.005	-10000	0	-10000	0	0
PRKCG	-0.13	0.23	0.36	5	-0.44	209	214
PRKCQ	0.022	0.044	-10000	0	-0.36	8	8
FKBP38/BCL2	0.025	0.042	-10000	0	-0.25	11	11
EP300	0.026	0.008	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
NFATc/JNK1	-0.007	0.13	0.31	3	-0.36	40	43
CaM/Ca2+/FKBP38	0.035	0.015	-10000	0	-0.22	1	1
FKBP12/FK506	0.017	0.008	-10000	0	-10000	0	0
CSNK1A1	0.014	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.022	0.053	-10000	0	-0.2	31	31
NFATc/ERK1	-0.008	0.13	0.34	2	-0.36	41	43
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.039	0.12	-10000	0	-0.33	41	41
NR4A1	0.038	0.073	0.25	5	-0.38	10	15
GSK3B	0.028	0.002	-10000	0	-10000	0	0
positive T cell selection	0.02	0.008	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.031	0.039	0.16	1	-10000	0	1
RCH1/ KPNB1	0.04	0.007	-10000	0	-10000	0	0
YWHAQ	0.028	0.002	-10000	0	-10000	0	0
PRKACA	0.028	0.003	-10000	0	-10000	0	0
AKAP5	0.011	0.075	-10000	0	-0.36	24	24
MEF2D	0.027	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.009	0.13	0.34	2	-0.36	42	44
CREBBP	0.027	0.007	-10000	0	-10000	0	0
BCL2	0.014	0.05	-10000	0	-0.36	10	10

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.056	0.32	0.47	1	-1.2	44	45
PLK1	0.02	0.12	0.4	1	-0.57	7	8
CDKN1B	0.057	0.12	0.37	8	-0.35	11	19
FOXO3	0.026	0.13	-10000	0	-0.54	11	11
KAT2B	0.015	0.08	-10000	0	-0.36	26	26
FOXO1/SIRT1	0.019	0.12	0.27	3	-0.36	41	44
CAT	0.02	0.12	-10000	0	-0.58	5	5
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.025	0.029	-10000	0	-10000	0	0
FOXO1	0.009	0.13	0.38	5	-0.38	44	49
MAPK10	0.012	0.08	0.19	47	-0.19	15	62
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.037	0.076	0.31	7	-10000	0	7
response to oxidative stress	0.004	0.017	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.038	0.12	-10000	0	-0.5	9	9
XPO1	0.028	0	-10000	0	-10000	0	0
EP300	0.02	0.026	-10000	0	-10000	0	0
BCL2L11	0.031	0.024	-10000	0	-10000	0	0
FOXO1/SKP2	0.018	0.12	0.27	4	-0.36	44	48
mol:GDP	0.004	0.017	-10000	0	-10000	0	0
RAN	0.029	0.003	-10000	0	-10000	0	0
GADD45A	0.043	0.13	-10000	0	-0.55	20	20
YWHAQ	0.028	0.002	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.041	0.12	0.28	4	-0.4	21	25
MST1	-0.043	0.17	-10000	0	-0.44	98	98
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.027	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.006	0.11	-10000	0	-0.38	32	32
YWHAB	0.016	0.014	-10000	0	-10000	0	0
MAPK8	0.036	0.05	0.19	55	-10000	0	55
MAPK9	0.036	0.05	0.19	55	-10000	0	55
YWHAG	0.027	0.006	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
SIRT1	0.028	0.014	-10000	0	-10000	0	0
SOD2	0.053	0.11	0.44	4	-0.54	1	5
RBL2	0.044	0.11	-10000	0	-0.72	2	2
RAL/GDP	0.037	0.023	-10000	0	-10000	0	0
CHUK	0.031	0.017	-10000	0	-10000	0	0
Ran/GTP	0.023	0.002	-10000	0	-10000	0	0
CSNK1G2	0.027	0.016	-10000	0	-0.36	1	1
RAL/GTP	0.04	0.022	-10000	0	-10000	0	0
CSNK1G1	0.026	0.017	-10000	0	-0.36	1	1
FASLG	-0.035	0.29	-10000	0	-1.2	33	33
SKP2	0.027	0.004	-10000	0	-10000	0	0
USP7	0.028	0.004	-10000	0	-10000	0	0
IKBKB	0.029	0.018	-10000	0	-10000	0	0
CCNB1	0.022	0.12	-10000	0	-0.58	5	5
FOXO1-3a-4/beta catenin	0.065	0.12	0.33	22	-10000	0	22
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.12	0.27	4	-0.35	44	48
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
SGK1	0.017	0.077	-10000	0	-0.36	24	24
CSNK1G3	0.027	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.042	0.004	-10000	0	-10000	0	0
ZFAND5	0.036	0.072	0.35	4	-10000	0	4
SFN	0.025	0.023	-10000	0	-0.36	2	2
CDK2	0.019	0.034	-10000	0	-10000	0	0
FOXO3A/14-3-3	0	0.097	-10000	0	-0.4	19	19
CREBBP	0.018	0.034	-10000	0	-10000	0	0
FBXO32	0.048	0.16	-10000	0	-0.98	2	2
BCL6	0.044	0.11	-10000	0	-0.82	1	1
RALB	0.029	0.001	-10000	0	-10000	0	0
RALA	0.026	0.008	-10000	0	-10000	0	0
YWHAH	0.027	0.006	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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
PLAUR	0.015	0.028	-10000	0	-10000	0	0
regulation of axonogenesis	-0.009	0.027	0.23	7	-10000	0	7
myoblast fusion	-0.029	0.019	-10000	0	-10000	0	0
mol:GTP	0.016	0.032	-10000	0	-0.15	22	22
regulation of calcium-dependent cell-cell adhesion	-0.02	0.085	0.21	59	-10000	0	59
ARF1/GTP	0.029	0.036	-10000	0	-10000	0	0
mol:GM1	0.004	0.027	-10000	0	-10000	0	0
mol:Choline	0.008	0.015	-10000	0	-0.19	1	1
lamellipodium assembly	0.004	0.082	-10000	0	-0.34	32	32
MAPK3	0.018	0.026	-10000	0	-0.22	1	1
ARF6/GTP/NME1/Tiam1	0.021	0.086	-10000	0	-0.21	59	59
ARF1	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.029	0.019	-10000	0	-10000	0	0
ARF1/GDP	0.024	0.058	-10000	0	-0.24	8	8
ARF6	0.032	0.009	-10000	0	-10000	0	0
RAB11A	0.027	0.006	-10000	0	-10000	0	0
TIAM1	-0.01	0.11	-10000	0	-0.36	59	59
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.024	-10000	0	-10000	0	0
actin filament bundle formation	-0.026	0.058	0.24	8	-10000	0	8
KALRN	0.02	0.017	-10000	0	-0.18	1	1
RAB11FIP3/RAB11A	0.039	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.058	-10000	0	-0.24	8	8
NME1	0.023	0.057	0.36	2	-0.44	8	10
Rac1/GDP	0.025	0.056	-10000	0	-0.24	7	7
substrate adhesion-dependent cell spreading	0.016	0.032	-10000	0	-0.15	22	22
cortical actin cytoskeleton organization	0.005	0.081	-10000	0	-0.34	30	30
RAC1	0.025	0.008	-10000	0	-10000	0	0
liver development	0.016	0.032	-10000	0	-0.15	22	22
ARF6/GTP	0.016	0.032	-10000	0	-0.15	22	22
RhoA/GTP	0.029	0.036	-10000	0	-10000	0	0
mol:GDP	0.012	0.05	-10000	0	-0.2	27	27
ARF6/GTP/RAB11FIP3/RAB11A	0.043	0.037	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
PLD1	0.013	0.034	-10000	0	-0.22	2	2
RAB11FIP3	0.027	0.004	-10000	0	-10000	0	0
tube morphogenesis	0.004	0.082	-10000	0	-0.34	32	32
ruffle organization	0.009	0.027	-10000	0	-0.23	7	7
regulation of epithelial cell migration	0.016	0.032	-10000	0	-0.15	22	22
PLD2	0.016	0.017	-10000	0	-10000	0	0
PIP5K1A	0.009	0.027	-10000	0	-0.23	7	7
mol:Phosphatidic acid	0.008	0.015	-10000	0	-0.19	1	1
Rac1/GTP	0.005	0.081	-10000	0	-0.34	30	30

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.1	0.17	-10000	0	-0.39	103	103
CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.007	-10000	0	-10000	0	0
AKT2	0.027	0.004	-10000	0	-10000	0	0
STXBP4	0.026	0.016	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.12	0.17	-10000	0	-0.41	115	115
YWHAZ	0.024	0.01	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
YWHAQ	0.028	0.002	-10000	0	-10000	0	0
TBC1D4	0.01	0.012	-10000	0	-0.25	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.006	-10000	0	-10000	0	0
YWHAB	0.016	0.014	-10000	0	-10000	0	0
SNARE/Synip	0.045	0.025	-10000	0	-0.21	1	1
YWHAG	0.027	0.006	-10000	0	-10000	0	0
ASIP	0.005	0.045	0.36	5	-0.44	2	7
PRKCI	0.026	0.022	-10000	0	-0.36	2	2
AS160/CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
RHOQ	0.028	0.002	-10000	0	-10000	0	0
GYS1	0.011	0.004	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
TRIP10	0.027	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.037	0.006	-10000	0	-10000	0	0
AS160/14-3-3	0.013	0.042	-10000	0	-0.24	5	5
VAMP2	0.023	0.011	-10000	0	-10000	0	0
SLC2A4	-0.14	0.19	-10000	0	-0.46	116	116
STX4	0.027	0.003	-10000	0	-10000	0	0
GSK3B	0.02	0.007	-10000	0	-10000	0	0
SFN	0.025	0.023	-10000	0	-0.36	2	2
LNPEP	0.027	0.006	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.024	0.058	-10000	0	-0.36	13	13
PDGF/PDGFRA/CRKL	0.036	0.043	-10000	0	-0.24	13	13
positive regulation of JUN kinase activity	0.062	0.041	-10000	0	-10000	0	0
CRKL	0.027	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.029	0.049	-10000	0	-0.26	16	16
AP1	0.023	0.098	0.3	5	-0.6	6	11
mol:IP3	0.004	0.036	-10000	0	-0.25	11	11
PLCG1	0.004	0.036	-10000	0	-0.25	11	11
PDGF/PDGFRA/alphaV Integrin	0.038	0.043	-10000	0	-0.24	13	13
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1
CRK	0.023	0.01	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.036	-10000	0	-0.25	11	11
CAV3	-0.013	0.035	-10000	0	-0.44	3	3
CAV1	0.019	0.054	-10000	0	-0.36	12	12
SHC/Grb2/SOS1	0.064	0.042	-10000	0	-10000	0	0
PDGF/PDGFRA/Shf	0.027	0.07	-10000	0	-0.28	28	28
FOS	-0.004	0.08	0.31	14	-0.63	5	19
JUN	-0.006	0.021	-10000	0	-10000	0	0
oligodendrocyte development	0.037	0.043	-10000	0	-0.24	13	13
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:DAG	0.004	0.036	-10000	0	-0.25	11	11
PDGF/PDGFRA	0.024	0.058	-10000	0	-0.36	13	13
actin cytoskeleton reorganization	0.037	0.047	0.26	1	-0.25	14	15
SRF	0.004	0.012	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.051	0.04	-10000	0	-0.2	10	10
PDGF/PDGFRA/Crk/C3G	0.044	0.042	-10000	0	-0.2	11	11
JAK1	0.012	0.037	-10000	0	-0.24	12	12
ELK1/SRF	0.026	0.077	0.16	140	-10000	0	140
SHB	0.026	0.03	0.36	1	-0.44	2	3
SHF	0.015	0.072	-10000	0	-0.44	15	15
CSNK2A1	0.012	0.021	-10000	0	-10000	0	0
GO:0007205	-0.001	0.038	-10000	0	-0.28	11	11
SOS1	0.028	0.002	-10000	0	-10000	0	0
Ras protein signal transduction	0.062	0.041	-10000	0	-10000	0	0
PDGF/PDGFRA/SHB	0.037	0.047	0.26	1	-0.25	14	15
PDGF/PDGFRA/Caveolin-1	0.032	0.057	-10000	0	-0.26	20	20
ITGAV	0.028	0.002	-10000	0	-10000	0	0
ELK1	-0.006	0.034	0.25	1	-0.24	10	11
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
PDGF/PDGFRA/Crk	0.031	0.043	-10000	0	-0.23	13	13
JAK-STAT cascade	0.012	0.037	-10000	0	-0.24	12	12
cell proliferation	0.027	0.069	-10000	0	-0.28	28	28

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.018	0.12	-10000	0	-0.36	64	64
CLTC	-0.002	0.1	0.19	1	-0.4	37	38
calcium ion-dependent exocytosis	0.012	0.043	-10000	0	-10000	0	0
Dynamin 2/GTP	0.023	0.031	0.18	1	-0.23	8	9
EXOC4	0.027	0.006	-10000	0	-10000	0	0
CD59	0.002	0.075	-10000	0	-0.32	29	29
CPE	-0.002	0.057	-10000	0	-0.21	42	42
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
membrane fusion	0.018	0.027	-10000	0	-10000	0	0
CTNND1	0.009	0.032	0.18	7	-0.22	8	15
DNM2	0.027	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.004	0.064	-10000	0	-0.24	30	30
TSHR	0.006	0.019	-10000	0	-0.27	2	2
INS	0.006	0.045	-10000	0	-0.49	4	4
BIN1	0.027	0.016	-10000	0	-0.36	1	1
mol:Choline	0.018	0.027	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.032	0.23	1	-0.26	8	9
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.022	0.031	0.18	1	-0.23	8	9
JUP	0.002	0.074	0.21	1	-0.31	29	30
ASAP2/amphiphysin II	0.049	0.017	-10000	0	-0.19	1	1
ARF6/GTP	0.019	0.005	-10000	0	-10000	0	0
CDH1	0.002	0.074	-10000	0	-0.31	29	29
clathrin-independent pinocytosis	0.019	0.005	-10000	0	-10000	0	0
MAPK8IP3	0.026	0.025	-10000	0	-0.4	2	2
positive regulation of endocytosis	0.019	0.005	-10000	0	-10000	0	0
EXOC2	0.027	0.016	-10000	0	-0.36	1	1
substrate adhesion-dependent cell spreading	0.024	0.041	-10000	0	-0.37	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.027	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.02	0.093	0.32	35	-10000	0	35
positive regulation of phagocytosis	0.013	0.005	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.034	0.019	-10000	0	-0.24	2	2
ACAP1	0.018	0.03	-10000	0	-0.28	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.036	0.11	-10000	0	-0.39	32	32
clathrin heavy chain/ACAP1	0.001	0.09	0.19	4	-0.33	35	39
JIP4/KLC1	0.048	0.016	-10000	0	-10000	0	0
EXOC1	0.026	0.016	-10000	0	-0.36	1	1
exocyst	0.024	0.041	-10000	0	-0.37	4	4
RALA/GTP	0.019	0.006	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.01	-10000	0	-10000	0	0
receptor recycling	0.019	0.005	-10000	0	-10000	0	0
CTNNA1	0.009	0.032	0.18	7	-0.22	8	15
NME1	0.01	0.032	0.23	1	-0.26	8	9
clathrin coat assembly	-0.002	0.1	0.19	1	-0.39	37	38
IL2RA	-0.001	0.076	-10000	0	-0.31	30	30
VAMP3	0.013	0.005	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.006	0.098	0.2	1	-0.3	38	39
EXOC6	0.027	0.006	-10000	0	-10000	0	0
PLD1	0.013	0.011	-10000	0	-0.23	1	1
PLD2	0.012	0.007	-10000	0	-10000	0	0
EXOC5	0.024	0.028	-10000	0	-0.36	3	3
PIP5K1C	0.007	0.055	0.14	1	-0.22	25	26
SDC1	0.002	0.074	-10000	0	-0.31	29	29
ARF6/GDP	0.021	0.033	0.2	1	-0.26	8	9
EXOC7	0.027	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.023	0.096	-10000	0	-0.33	35	35
mol:Phosphatidic acid	0.018	0.027	-10000	0	-10000	0	0
endocytosis	-0.048	0.016	0.19	1	-10000	0	1
SCAMP2	0.027	0.006	-10000	0	-10000	0	0
ADRB2	-0.028	0.12	0.39	1	-0.41	40	41
EXOC3	0.027	0.004	-10000	0	-10000	0	0
ASAP2	0.028	0.002	-10000	0	-10000	0	0
Dynamin 2/GDP	0.026	0.032	0.21	1	-0.23	8	9
KLC1	0.026	0.007	-10000	0	-10000	0	0
AVPR2	-0.014	0.11	0.26	7	-0.39	38	45
RALA	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.018	0.09	-10000	0	-0.32	32	32

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.021	0.054	-10000	0	-0.33	1	1
BAG4	0.024	0.01	-10000	0	-10000	0	0
BAD	0.013	0.028	0.15	4	-0.33	1	5
NFKBIA	0.026	0.007	-10000	0	-10000	0	0
BIRC3	0.02	0.05	-10000	0	-0.37	10	10
BAX	0.014	0.037	0.2	11	-0.18	1	12
EnzymeConsortium:3.1.4.12	0.008	0.017	0.092	5	-0.076	1	6
IKBKB	0.033	0.067	0.21	30	-0.31	1	31
MAP2K2	0.013	0.041	0.18	20	-0.28	1	21
MAP2K1	0.012	0.039	0.18	19	-10000	0	19
SMPD1	0.009	0.026	0.14	4	-0.16	7	11
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.026	0.058	0.21	2	-0.33	2	4
MAP2K4	0.009	0.026	0.17	3	-0.21	1	4
protein ubiquitination	0.027	0.06	0.32	3	-0.3	2	5
EnzymeConsortium:2.7.1.37	0.014	0.042	0.18	20	-0.22	1	21
response to UV	0	0	0.002	21	-10000	0	21
RAF1	0.015	0.04	0.18	19	-10000	0	19
CRADD	0.027	0.003	-10000	0	-10000	0	0
mol:ceramide	0.015	0.029	0.12	10	-0.18	1	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0.034	0.011	-10000	0	-10000	0	0
MADD	0.028	0.003	-10000	0	-10000	0	0
MAP3K1	0.012	0.029	0.14	6	-0.2	2	8
TRADD	0.028	0.003	-10000	0	-10000	0	0
RELA/p50	0.027	0.004	-10000	0	-10000	0	0
MAPK3	0.017	0.041	0.18	19	-0.23	1	20
MAPK1	0.013	0.043	0.18	18	-0.23	1	19
p50/RELA/I-kappa-B-alpha	0.038	0.012	-10000	0	-10000	0	0
FADD	0.023	0.052	0.21	2	-0.29	2	4
KSR1	0.016	0.039	0.18	19	-0.18	1	20
MAPK8	0.009	0.029	0.21	3	-10000	0	3
TRAF2	0.027	0.016	-10000	0	-0.36	1	1
response to radiation	0	0	0.002	6	-10000	0	6
CHUK	0.019	0.051	0.24	1	-0.29	1	2
TNF R/SODD	0.035	0.015	-10000	0	-10000	0	0
TNF	0.024	0.035	-10000	0	-0.36	5	5
CYCS	0.037	0.05	0.14	47	-0.26	1	48
IKBKG	0.021	0.056	0.22	3	-0.35	2	5
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.026	0.055	-10000	0	-0.3	3	3
RELA	0.027	0.004	-10000	0	-10000	0	0
RIPK1	0.027	0.004	-10000	0	-10000	0	0
AIFM1	0.032	0.046	0.14	40	-0.26	1	41
TNF/TNF R/SODD	0.045	0.031	-10000	0	-0.21	5	5
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
response to heat	0	0	0.002	6	-10000	0	6
CASP8	0.023	0.098	-10000	0	-0.56	16	16
NSMAF	0.038	0.072	0.21	57	-0.32	1	58
response to hydrogen peroxide	0	0	0.002	21	-10000	0	21
BCL2	0.014	0.05	-10000	0	-0.36	10	10

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.05	0.24	-10000	0	-0.91	3	3
PLK1	0.039	0.081	-10000	0	-0.84	4	4
BIRC5	0.034	0.1	-10000	0	-0.81	8	8
HSPA1B	0.04	0.25	-10000	0	-0.87	5	5
MAP2K1	0.031	0.038	-10000	0	-10000	0	0
BRCA2	0.089	0.25	0.61	1	-0.91	3	4
FOXM1	0.05	0.26	-10000	0	-1	6	6
XRCC1	0.052	0.24	0.61	1	-0.91	3	4
FOXM1B/p19	0.015	0.27	-10000	0	-0.94	9	9
Cyclin D1/CDK4	0.058	0.23	-10000	0	-0.92	3	3
CDC2	0.051	0.25	-10000	0	-0.89	6	6
TGFA	0.047	0.22	-10000	0	-0.96	3	3
SKP2	0.052	0.24	-10000	0	-0.99	2	2
CCNE1	0.028	0.037	0.35	3	-0.44	2	5
CKS1B	0.051	0.24	-10000	0	-0.85	6	6
RB1	0.05	0.13	-10000	0	-0.67	3	3
FOXM1C/SP1	0.055	0.26	-10000	0	-0.93	6	6
AURKB	-0.096	0.33	-10000	0	-0.8	105	105
CENPF	0.053	0.24	-10000	0	-0.95	3	3
CDK4	0.029	0.026	-10000	0	-0.42	1	1
MYC	0.039	0.21	-10000	0	-0.82	2	2
CHEK2	0.032	0.038	-10000	0	-10000	0	0
ONECUT1	0.048	0.23	-10000	0	-0.96	3	3
CDKN2A	-0.064	0.19	0.35	2	-0.45	115	117
LAMA4	0.05	0.24	-10000	0	-0.91	3	3
FOXM1B/HNF6	0.046	0.25	-10000	0	-1.1	3	3
FOS	0.04	0.27	-10000	0	-1	13	13
SP1	0.027	0.009	-10000	0	-10000	0	0
CDC25B	0.067	0.25	0.61	1	-0.95	4	5
response to radiation	0.011	0.021	-10000	0	-10000	0	0
CENPB	0.073	0.24	0.61	1	-0.91	3	4
CENPA	0.049	0.24	-10000	0	-0.95	3	3
NEK2	0.053	0.24	-10000	0	-0.95	3	3
HIST1H2BA	0.046	0.24	-10000	0	-0.91	3	3
CCNA2	0.028	0.012	-10000	0	-10000	0	0
EP300	0.026	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.046	0.26	-10000	0	-0.99	5	5
CCNB2	0.05	0.24	-10000	0	-0.95	3	3
CCNB1	0.05	0.25	-10000	0	-0.92	5	5
ETV5	0.049	0.24	-10000	0	-0.95	3	3
ESR1	-0.012	0.39	-10000	0	-1.1	58	58
CCND1	0.047	0.23	-10000	0	-0.93	3	3
GSK3A	0.03	0.034	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.061	0.044	0.24	3	-0.26	2	5
CDK2	0.029	0.011	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.012	0.025	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.06	0.25	-10000	0	-0.88	6	6
GAS1	-0.057	0.45	-10000	0	-1	93	93
MMP2	0.047	0.25	-10000	0	-1.1	5	5
RB1/FOXM1C	0.041	0.22	-10000	0	-0.92	3	3
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.036	0.036	0.26	1	-0.31	6	7
CRKL	0.027	0.096	0.27	11	-0.42	16	27
mol:PIP3	-0.002	0.011	-10000	0	-10000	0	0
AKT1	-0.007	0.02	-10000	0	-10000	0	0
PTK2B	0.02	0.025	-10000	0	-0.36	2	2
RAPGEF1	0.03	0.095	0.27	15	-0.42	14	29
RANBP10	0.028	0.002	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
HGF/MET/SHIP2	0.044	0.053	-10000	0	-0.24	18	18
MAP3K5	0.017	0.12	0.29	9	-0.44	20	29
HGF/MET/CIN85/CBL/ENDOPHILINS	0.057	0.053	-10000	0	-0.27	6	6
AP1	0.029	0.035	-10000	0	-0.22	4	4
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
apoptosis	-0.035	0.23	-10000	0	-0.72	58	58
STAT3 (dimer)	0.003	0.051	-10000	0	-0.33	6	6
GAB1/CRKL/SHP2/PI3K	0.065	0.093	0.3	4	-0.41	12	16
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
CBL/CRK	0.048	0.093	0.26	11	-0.41	14	25
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0.014	-10000	0	-10000	0	0
PTEN	0.026	0.006	-10000	0	-10000	0	0
ELK1	0.005	0.094	0.36	29	-10000	0	29
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.007	0.04	-10000	0	-0.22	7	7
PAK1	-0.008	0.022	-10000	0	-10000	0	0
HGF/MET/RANBP10	0.045	0.053	-10000	0	-0.24	19	19
HRAS	0.02	0.061	0.32	1	-0.47	3	4
DOCK1	0.028	0.091	0.26	11	-0.42	14	25
GAB1	0.018	0.087	-10000	0	-0.45	15	15
CRK	0.024	0.09	0.27	9	-0.43	13	22
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.079	-10000	0	-0.43	15	15
JUN	0.027	0.004	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.012	0.039	-10000	0	-0.18	17	17
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
cell morphogenesis	0.049	0.1	0.26	43	-0.42	4	47
GRB2/SHC	0.009	0.054	-10000	0	-0.21	5	5
FOS	0.022	0.039	-10000	0	-0.36	6	6
GLMN	0.001	0.012	-10000	0	-0.21	2	2
cell motility	0.004	0.094	0.35	29	-10000	0	29
HGF/MET/MUC20	0.027	0.049	-10000	0	-0.24	19	19
cell migration	0.008	0.053	-10000	0	-0.2	5	5
GRB2	0.027	0.004	-10000	0	-10000	0	0
CBL	0.027	0.004	-10000	0	-10000	0	0
MET/RANBP10	0.037	0.034	0.26	1	-0.32	5	6
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.014	0.047	-10000	0	-0.3	8	8
MET/MUC20	0.017	0.032	0.24	1	-0.31	5	6
RAP1B	0.028	0.092	0.27	16	-0.4	14	30
RAP1A	0.027	0.09	0.27	11	-0.4	14	25
HGF/MET/RANBP9	0.044	0.054	-10000	0	-0.24	20	20
RAF1	0.023	0.065	0.31	1	-0.48	2	3
STAT3	0.004	0.051	-10000	0	-0.35	5	5
cell proliferation	0.03	0.074	0.33	2	-0.39	5	7
RPS6KB1	0.003	0.036	-10000	0	-0.29	7	7
MAPK3	-0.013	0.083	0.53	8	-10000	0	8
MAPK1	0.016	0.16	0.65	32	-10000	0	32
RANBP9	0.027	0.016	-10000	0	-0.36	1	1
MAPK8	0.028	0.11	0.33	6	-0.44	12	18
SRC	0.005	0.039	-10000	0	-0.3	6	6
PI3K	0.009	0.054	-10000	0	-0.22	1	1
MET/Glomulin	-0.014	0.052	0.2	1	-0.2	17	18
SOS1	0.028	0.002	-10000	0	-10000	0	0
MAP2K1	0.021	0.061	0.31	2	-0.45	2	4
MET	0.023	0.045	0.36	1	-0.44	5	6
MAP4K1	0.018	0.12	0.27	9	-0.46	21	30
PTK2	0.023	0.01	-10000	0	-10000	0	0
MAP2K2	0.022	0.064	0.31	2	-0.45	2	4
BAD	-0.008	0.021	-10000	0	-10000	0	0
MAP2K4	0.013	0.11	0.31	7	-0.43	14	21
SHP2/GRB2/SOS1/GAB1	0.049	0.083	0.25	1	-0.38	14	15
INPPL1	0.027	0.004	-10000	0	-10000	0	0
PXN	0.028	0.002	-10000	0	-10000	0	0
SH3KBP1	0.027	0.004	-10000	0	-10000	0	0
HGS	-0.014	0.035	-10000	0	-0.2	7	7
PLCgamma1/PKC	0.012	0.01	-10000	0	-10000	0	0
HGF	0.017	0.061	-10000	0	-0.37	15	15
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.028	0.002	-10000	0	-10000	0	0
PTPRJ	0.028	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.025	0.039	-10000	0	-0.26	1	1
PDPK1	-0.005	0.023	-10000	0	-10000	0	0
HGF/MET/SHIP	0.044	0.054	-10000	0	-0.3	6	6

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.04	0.05	-10000	0	-0.21	20	20
forebrain development	0.001	0.085	0.38	1	-0.5	6	7
GNAO1	-0.12	0.19	-10000	0	-0.36	225	225
SMO/beta Arrestin2	0.034	0.018	-10000	0	-10000	0	0
SMO	0.027	0.007	-10000	0	-10000	0	0
ARRB2	0.024	0.011	-10000	0	-10000	0	0
GLI3/SPOP	0.038	0.094	-10000	0	-0.36	7	7
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.028	0.002	-10000	0	-10000	0	0
GNAI2	0.028	0.005	-10000	0	-10000	0	0
SIN3/HDAC complex	0.05	0.032	-10000	0	-10000	0	0
GNAI1	0.015	0.067	-10000	0	-0.36	19	19
XPO1	0.029	0.008	-10000	0	-10000	0	0
GLI1/Su(fu)	0	0.088	-10000	0	-0.57	3	3
SAP30	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.027	0.007	-10000	0	-10000	0	0
MIM/GLI2A	0.022	0.039	-10000	0	-0.36	5	5
IFT88	0.021	0.012	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GLI2	0.012	0.058	0.18	2	-0.26	16	18
GLI3	0.026	0.095	0.25	4	-0.35	9	13
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.027	0.006	-10000	0	-10000	0	0
SAP18	0.021	0.012	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.021	0.012	-10000	0	-10000	0	0
GNG2	0.011	0.074	-10000	0	-0.36	23	23
Gi family/GTP	-0.059	0.12	-10000	0	-0.32	45	45
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.026	0.006	-10000	0	-10000	0	0
GLI3/Su(fu)	0.033	0.084	0.27	3	-0.34	8	11
GLI2/Su(fu)	0.021	0.063	-10000	0	-0.35	8	8
FOXA2	0	0.14	-10000	0	-0.61	21	21
neural tube patterning	0.001	0.085	0.38	1	-0.5	6	7
SPOP	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.028	0.039	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
CSNK1G2	0.027	0.016	-10000	0	-0.36	1	1
CSNK1G3	0.027	0.005	-10000	0	-10000	0	0
MTSS1	0.022	0.039	-10000	0	-0.36	5	5
embryonic limb morphogenesis	0.001	0.085	0.38	1	-0.5	6	7
SUFU	0.021	0.011	-10000	0	-10000	0	0
LGALS3	0.025	0.017	-10000	0	-0.36	1	1
catabolic process	0.042	0.1	-10000	0	-0.4	10	10
GLI3A/CBP	0.032	0.025	-10000	0	-0.31	3	3
KIF3A	0.027	0.005	-10000	0	-10000	0	0
GLI1	0.001	0.087	0.38	1	-0.51	6	7
RAB23	0.026	0.022	-10000	0	-0.36	2	2
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
IFT172	0.028	0	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.029	0.039	-10000	0	-10000	0	0
GNAZ	0.024	0.035	-10000	0	-0.36	5	5
RBBP4	0.027	0.005	-10000	0	-10000	0	0
CSNK1G1	0.026	0.017	-10000	0	-0.36	1	1
PIAS1	0.026	0.006	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.026	0.058	-10000	0	-0.28	8	8
STK36	0.029	0.008	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.061	0.13	-10000	0	-0.33	74	74
PTCH1	0.001	0.098	0.36	1	-0.98	3	4
MIM/GLI1	0.008	0.098	0.37	1	-0.54	6	7
CREBBP	0.032	0.024	-10000	0	-0.31	3	3
Su(fu)/SIN3/HDAC complex	0.027	0.082	-10000	0	-0.34	19	19

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.023	0.059	-10000	0	-10000	0	0
CRKL	0.022	0.052	0.3	4	-0.29	2	6
mol:DAG	0.018	0.031	-10000	0	-10000	0	0
HRAS	0.008	0.06	0.3	6	-0.3	1	7
MAPK8	0.035	0.063	0.19	59	-10000	0	59
RAP1A	0.021	0.052	0.33	3	-0.29	2	5
GAB1	0.021	0.052	0.31	3	-0.29	2	5
MAPK14	0.035	0.062	0.19	57	-10000	0	57
EPO	0.02	0.048	0.33	2	-0.45	5	7
PLCG1	0.018	0.032	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.027	0.022	-10000	0	-0.41	1	1
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1
EPO/EPOR (dimer)/SOCS3	0.047	0.042	0.23	2	-0.26	8	10
GAB1/SHC/GRB2/SOS1	0.051	0.05	0.26	1	-0.31	1	2
EPO/EPOR (dimer)	0.034	0.041	0.24	2	-0.31	6	8
IRS2	0.014	0.039	0.23	1	-0.34	1	2
STAT1	0.03	0.049	-10000	0	-10000	0	0
STAT5B	0.028	0.045	-10000	0	-10000	0	0
cell proliferation	0.015	0.074	0.19	83	-10000	0	83
GAB1/SHIP/PIK3R1/SHP2/SHC	0.041	0.044	-10000	0	-0.3	1	1
TEC	0.02	0.052	0.31	3	-0.29	2	5
SOCS3	0.026	0.027	-10000	0	-0.44	2	2
STAT1 (dimer)	0.031	0.05	-10000	0	-10000	0	0
JAK2	0.026	0.03	-10000	0	-0.37	3	3
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.065	0.053	0.24	1	-0.3	2	3
EPO/EPOR	0.034	0.041	0.24	2	-0.31	6	8
LYN	0.024	0.013	-10000	0	-10000	0	0
TEC/VAV2	0.031	0.052	-10000	0	-0.26	1	1
elevation of cytosolic calcium ion concentration	0.027	0.022	-10000	0	-0.41	1	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.046	0.041	0.24	2	-0.25	5	7
mol:IP3	0.018	0.031	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.035	0.046	0.24	1	-0.32	1	2
SH2B3	0.028	0.011	-10000	0	-10000	0	0
NFKB1	0.034	0.062	0.19	59	-0.23	4	63
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.028	-10000	0	-0.24	3	3
PTPN6	0.021	0.05	0.3	2	-0.3	2	4
TEC/VAV2/GRB2	0.043	0.056	0.26	1	-10000	0	1
EPOR	0.027	0.022	-10000	0	-0.41	1	1
INPP5D	0.027	0.016	-10000	0	-0.36	1	1
mol:GDP	0.05	0.05	0.26	1	-0.32	1	2
SOS1	0.028	0.002	-10000	0	-10000	0	0
PLCG2	-0.004	0.1	-10000	0	-0.36	49	49
CRKL/CBL/C3G	0.047	0.049	0.26	2	-10000	0	2
VAV2	0.018	0.056	0.3	4	-0.25	2	6
CBL	0.02	0.052	0.3	4	-0.34	1	5
SHC/Grb2/SOS1	0.038	0.042	-10000	0	-0.32	1	1
STAT5A	0.028	0.045	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.041	0.068	-10000	0	-0.32	1	1
LYN/PLCgamma2	0.016	0.075	-10000	0	-0.25	43	43
PTPN11	0.028	0.002	-10000	0	-10000	0	0
BTK	0.001	0.079	0.3	4	-0.31	6	10
BCL2	0.007	0.17	0.34	1	-0.68	32	33

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.035	0.082	-10000	0	-0.2	54	54
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.027	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.029	0.074	0.3	1	-0.36	1	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.041	-10000	0	-0.22	3	3
antigen processing and presentation of peptide antigen via MHC class I	-0.005	0.054	-10000	0	-0.26	1	1
CaM/Ca2+	0.034	0.08	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.012	0.073	-10000	0	-0.39	1	1
AKT1	-0.007	0.064	0.32	3	-10000	0	3
MAP2K1	-0.022	0.064	0.35	2	-0.24	1	3
MAP3K11	-0.004	0.07	0.35	2	-10000	0	2
IFNGR1	0.022	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.13	-10000	0	-0.36	56	56
Rap1/GTP	0.001	0.056	-10000	0	-10000	0	0
CRKL/C3G	0.038	0.015	-10000	0	-0.25	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.033	0.091	-10000	0	-0.22	52	52
CEBPB	0.021	0.14	0.33	6	-0.53	13	19
STAT3	0.027	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.036	0.12	-10000	0	-0.68	5	5
STAT1	-0.003	0.07	0.35	2	-0.39	1	3
CALM1	0.026	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.02	0.14	-10000	0	-0.44	60	60
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
STAT1 (dimer)/PIAS1	0.011	0.072	0.35	2	-0.38	1	3
CEBPB/PTGES2/Cbp/p300	0.028	0.092	-10000	0	-0.38	7	7
mol:Ca2+	0.032	0.08	-10000	0	-0.2	54	54
MAPK3	-0.003	0.09	0.39	1	-0.69	4	5
STAT1 (dimer)	0.001	0.075	-10000	0	-0.36	1	1
MAPK1	-0.031	0.17	0.41	1	-0.72	28	29
JAK2	0.02	0.033	-10000	0	-0.37	3	3
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
JAK1	0.022	0.02	-10000	0	-10000	0	0
CAMK2D	0.026	0.023	-10000	0	-0.36	2	2
DAPK1	0.014	0.14	0.33	8	-0.54	28	36
SMAD7	0.002	0.034	0.18	3	-0.22	1	4
CBL/CRKL/C3G	0.021	0.074	0.35	2	-10000	0	2
PI3K	0.034	0.079	-10000	0	-10000	0	0
IFNG	-0.02	0.14	-10000	0	-0.44	60	60
apoptosis	0.009	0.12	0.32	6	-0.42	35	41
CAMK2G	0.027	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.027	0.004	-10000	0	-10000	0	0
CAMK2A	-0.007	0.1	-10000	0	-0.36	49	49
CAMK2B	-0.013	0.11	0.36	1	-0.37	50	51
FRAP1	-0.019	0.058	0.3	3	-10000	0	3
PRKCD	-0.017	0.065	0.32	3	-10000	0	3
RAP1B	0.028	0.003	-10000	0	-10000	0	0
negative regulation of cell growth	-0.005	0.054	-10000	0	-0.26	1	1
PTPN2	0.022	0.011	-10000	0	-10000	0	0
EP300	0.027	0.006	-10000	0	-10000	0	0
IRF1	-0.007	0.063	0.33	4	-10000	0	4
STAT1 (dimer)/PIASy	0.01	0.072	0.4	1	-0.38	1	2
SOCS1	0.012	0.11	-10000	0	-1	5	5
mol:GDP	0.017	0.069	0.27	1	-10000	0	1
CASP1	0.001	0.038	0.18	3	-0.22	3	6
PTGES2	0.027	0.004	-10000	0	-10000	0	0
IRF9	0.024	0.052	0.19	12	-0.19	1	13
mol:PI-3-4-5-P3	0.021	0.071	-10000	0	-10000	0	0
RAP1/GDP	0.019	0.065	-10000	0	-10000	0	0
CBL	-0.006	0.069	0.35	2	-10000	0	2
MAP3K1	-0.003	0.07	0.36	2	-0.22	1	3
PIAS1	0.026	0.006	-10000	0	-10000	0	0
PIAS4	0.027	0.004	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.005	0.054	-10000	0	-0.26	1	1
PTPN11	-0.003	0.069	-10000	0	-0.21	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.024	0.01	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.03	0.069	-10000	0	-0.32	7	7
NEF	-0.004	0.033	-10000	0	-0.23	2	2
NFKBIA	0.026	0.016	-10000	0	-10000	0	0
BIRC3	0.013	0.056	-10000	0	-0.4	10	10
CYCS	0.012	0.078	0.18	50	-0.35	6	56
RIPK1	0.027	0.004	-10000	0	-10000	0	0
CD247	0.013	0.077	-10000	0	-0.26	37	37
MAP2K7	0.018	0.11	0.28	1	-0.62	12	13
protein ubiquitination	0.027	0.052	0.25	9	-0.29	1	10
CRADD	0.027	0.003	-10000	0	-10000	0	0
DAXX	0.027	0.004	-10000	0	-10000	0	0
FAS	0.022	0.044	-10000	0	-0.36	8	8
BID	0.004	0.069	0.19	9	-0.25	31	40
NF-kappa-B/RelA/I kappa B alpha	0.052	0.041	-10000	0	-0.23	9	9
TRADD	0.028	0.003	-10000	0	-10000	0	0
MAP3K5	0.027	0.004	-10000	0	-10000	0	0
CFLAR	0.028	0	-10000	0	-10000	0	0
FADD	0.027	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.052	0.041	-10000	0	-0.23	9	9
MAPK8	0.017	0.1	0.36	2	-0.57	12	14
APAF1	0.028	0.003	-10000	0	-10000	0	0
TRAF1	0.027	0.004	-10000	0	-10000	0	0
TRAF2	0.027	0.016	-10000	0	-0.36	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.01	0.073	0.2	9	-0.26	32	41
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.033	0.048	-10000	0	-0.36	2	2
CHUK	0.027	0.054	0.35	4	-0.3	2	6
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.073	0.037	-10000	0	-10000	0	0
TCRz/NEF	0.007	0.079	-10000	0	-0.29	38	38
TNF	0.024	0.035	-10000	0	-0.36	5	5
FASLG	-0.009	0.12	-10000	0	-0.47	34	34
NFKB1	0.027	0.016	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.045	0.031	-10000	0	-0.21	5	5
CASP6	0.033	0.1	-10000	0	-0.48	10	10
CASP7	0.015	0.09	0.35	2	-0.39	15	17
RELA	0.027	0.016	-10000	0	-10000	0	0
CASP2	0.027	0.005	-10000	0	-10000	0	0
CASP3	0.012	0.091	0.35	2	-0.42	14	16
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.035	0.015	-10000	0	-10000	0	0
CASP8	0.028	0.001	-10000	0	-10000	0	0
CASP9	0.026	0.007	-10000	0	-10000	0	0
MAP3K14	0.03	0.051	0.23	1	-0.33	2	3
APAF-1/Caspase 9	0.024	0.072	-10000	0	-0.3	4	4
BCL2	0.009	0.093	0.35	2	-0.52	11	13

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.011	0.071	-10000	0	-0.44	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.004	0.088	0.41	4	-10000	0	4
IL27/IL27R/JAK1	0.036	0.11	-10000	0	-0.54	1	1
TBX21	-0.02	0.12	-10000	0	-0.47	18	18
IL12B	0.015	0.041	-10000	0	-0.45	4	4
IL12A	0.002	0.03	-10000	0	-0.26	8	8
IL6ST	0.016	0.062	-10000	0	-0.37	15	15
IL27RA/JAK1	0.023	0.027	-10000	0	-10000	0	0
IL27	0.003	0.089	-10000	0	-0.44	23	23
TYK2	0.024	0.015	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.055	0.16	0.77	3	-10000	0	3
T-helper 2 cell differentiation	0.004	0.088	0.41	4	-10000	0	4
T cell proliferation during immune response	0.004	0.088	0.41	4	-10000	0	4
MAPKKK cascade	-0.004	0.088	-10000	0	-0.41	4	4
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT2	0.028	0.002	-10000	0	-10000	0	0
STAT1	0.027	0.019	-10000	0	-0.45	1	1
IL12RB1	0.014	0.07	-10000	0	-0.36	20	20
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.014	0.11	0.37	1	-0.51	10	11
IL27/IL27R/JAK2/TYK2	-0.004	0.089	-10000	0	-0.41	4	4
positive regulation of T cell mediated cytotoxicity	-0.004	0.088	-10000	0	-0.41	4	4
STAT1 (dimer)	0.042	0.15	-10000	0	-0.54	7	7
JAK2	0.022	0.031	-10000	0	-0.36	3	3
JAK1	0.027	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	0.007	0.093	-10000	0	-0.4	4	4
T cell proliferation	-0.043	0.11	0.45	1	-0.4	14	15
IL12/IL12R/TYK2/JAK2	0.002	0.15	-10000	0	-0.76	19	19
IL17A	-0.055	0.16	0.77	3	-10000	0	3
mast cell activation	0.004	0.088	0.41	4	-10000	0	4
IFNG	0.002	0.027	0.077	1	-0.11	2	3
T cell differentiation	-0.001	0.004	-10000	0	-0.017	3	3
STAT3 (dimer)	0.008	0.093	-10000	0	-0.4	4	4
STAT5A (dimer)	0.008	0.093	-10000	0	-0.4	4	4
STAT4 (dimer)	0.001	0.11	-10000	0	-0.37	16	16
STAT4	0.011	0.08	-10000	0	-0.36	27	27
T cell activation	-0.006	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.038	0.059	-10000	0	-10000	0	0
GATA3	-0.011	0.1	0.52	2	-1.2	4	6
IL18	0.004	0.018	-10000	0	-0.25	3	3
positive regulation of mast cell cytokine production	0.008	0.092	-10000	0	-0.39	4	4
IL27/EBI3	0.004	0.097	-10000	0	-0.28	61	61
IL27RA	0.008	0.022	-10000	0	-10000	0	0
IL6	-0.064	0.17	0.34	7	-0.46	77	84
STAT5A	0.027	0.004	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.016	0.013	-10000	0	-10000	0	0
IL1B	-0.024	0.093	-10000	0	-0.31	58	58
EBI3	0.002	0.095	-10000	0	-0.36	39	39
TNF	0.004	0.023	-10000	0	-0.25	5	5

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.019	0.056	-10000	0	-0.36	13	13
HRAS	0.027	0.016	-10000	0	-0.36	1	1
EGFR	0.024	0.023	-10000	0	-0.36	2	2
AKT	0.039	0.073	0.27	14	-0.28	6	20
FOXO3	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.007	-10000	0	-10000	0	0
FOXO1	0.021	0.019	-10000	0	-0.36	1	1
AKT3	0.021	0.047	-10000	0	-0.36	9	9
FOXO4	0.028	0.002	-10000	0	-10000	0	0
MET	0.023	0.045	0.36	1	-0.44	5	6
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
PIK3CB	0.028	0.014	0.36	1	-10000	0	1
NRAS	0.026	0.023	-10000	0	-0.36	2	2
PIK3CG	-0.031	0.14	-10000	0	-0.36	91	91
PIK3R3	0.027	0.004	-10000	0	-10000	0	0
PIK3R2	0.027	0.003	-10000	0	-10000	0	0
NF1	0.027	0.005	-10000	0	-10000	0	0
RAS	0.023	0.038	0.18	4	-0.28	1	5
ERBB2	0.033	0.044	0.36	11	-10000	0	11
proliferation/survival/translation	-0.025	0.071	0.26	17	-0.23	3	20
PI3K	0.025	0.065	0.23	24	-0.21	6	30
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
KRAS	0.026	0.016	-10000	0	-0.36	1	1
FOXO	0.062	0.055	0.22	24	-10000	0	24
AKT2	0.027	0.004	-10000	0	-10000	0	0
PTEN	0.026	0.006	-10000	0	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.001	0.13	-10000	0	-0.89	3	3
RAD9A	0.027	0.004	-10000	0	-10000	0	0
AP1	0.035	0.031	-10000	0	-0.25	6	6
IFNAR2	0.025	0.013	-10000	0	-10000	0	0
AKT1	-0.002	0.063	-10000	0	-0.29	15	15
ER alpha/Oestrogen	-0.005	0.077	-10000	0	-0.25	55	55
NFX1/SIN3/HDAC complex	0.039	0.047	-10000	0	-0.29	2	2
EGF	-0.057	0.16	-10000	0	-0.37	127	127
SMG5	0.027	0.004	-10000	0	-10000	0	0
SMG6	0.023	0.01	-10000	0	-10000	0	0
SP3/HDAC2	0.037	0.02	-10000	0	-10000	0	0
TERT/c-Abl	0.008	0.13	-10000	0	-0.74	4	4
SAP18	0.022	0.012	-10000	0	-10000	0	0
MRN complex	0.046	0.024	-10000	0	-10000	0	0
WT1	-0.2	0.24	0.35	3	-0.44	299	302
WRN	0.021	0.019	-10000	0	-0.36	1	1
SP1	0.025	0.016	-10000	0	-10000	0	0
SP3	0.028	0.004	-10000	0	-10000	0	0
TERF2IP	0.027	0.003	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.027	0.12	-10000	0	-0.9	2	2
Mad/Max	0.037	0.021	-10000	0	-0.25	2	2
TERT	-0.002	0.13	-10000	0	-0.93	3	3
CCND1	-0.001	0.12	-10000	0	-0.92	2	2
MAX	0.026	0.008	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
RBBP4	0.027	0.005	-10000	0	-10000	0	0
TERF2	0.025	0.009	-10000	0	-10000	0	0
PTGES3	0.028	0.002	-10000	0	-10000	0	0
SIN3A	0.027	0.006	-10000	0	-10000	0	0
Telomerase/911	0.041	0.045	0.22	1	-0.3	3	4
CDKN1B	-0.007	0.084	-10000	0	-0.26	60	60
RAD1	0.028	0.014	0.36	1	-10000	0	1
XRCC5	0.028	0.001	-10000	0	-10000	0	0
XRCC6	0.026	0.006	-10000	0	-10000	0	0
SAP30	0.027	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.037	0.012	-10000	0	-10000	0	0
UBE3A	0.025	0.017	-10000	0	-0.36	1	1
JUN	0.027	0.005	-10000	0	-10000	0	0
E6	0	0.002	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.017	0.015	-10000	0	-0.25	1	1
FOS	0.022	0.039	-10000	0	-0.36	6	6
IFN-gamma/IRF1	0.01	0.11	-10000	0	-0.31	60	60
PARP2	0.026	0.007	-10000	0	-10000	0	0
BLM	0.027	0.014	0.36	1	-10000	0	1
Telomerase	-0.001	0.11	-10000	0	-0.56	14	14
IRF1	0.03	0.006	-10000	0	-10000	0	0
ESR1	-0.008	0.11	-10000	0	-0.36	55	55
KU/TER	0.039	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.04	0.009	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.032	0.06	-10000	0	-0.29	6	6
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.033	0.061	-10000	0	-0.3	6	6
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.024	0.016	-10000	0	-10000	0	0
ATM	0.011	0.003	-10000	0	-10000	0	0
SMAD3	0.012	0.014	-10000	0	-0.32	1	1
ABL1	0.027	0.004	-10000	0	-10000	0	0
MXD1	0.026	0.022	-10000	0	-0.36	2	2
MRE11A	0.027	0.004	-10000	0	-10000	0	0
HUS1	0.025	0.008	-10000	0	-10000	0	0
RPS6KB1	0.026	0.016	-10000	0	-0.36	1	1
TERT/NF kappa B1/14-3-3	0.012	0.14	-10000	0	-0.68	6	6
NR2F2	0.026	0.007	-10000	0	-10000	0	0
MAPK3	-0.008	0.017	-10000	0	-0.27	1	1
MAPK1	-0.007	0.013	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.026	0.019	-10000	0	-0.44	1	1
NFKB1	0.027	0.005	-10000	0	-10000	0	0
HNRNPC	0.026	0.007	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.003	-10000	0	-10000	0	0
NBN	0.023	0.018	-10000	0	-0.36	1	1
EGFR	0.024	0.024	-10000	0	-0.36	2	2
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	-0.021	0.12	-10000	0	-0.26	115	115
MYC	0.027	0.049	0.36	9	-0.44	2	11
IL2	0.017	0.017	-10000	0	-10000	0	0
KU	0.039	0.009	-10000	0	-10000	0	0
RAD50	0.027	0.005	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
TGFB1	0.026	0.019	-10000	0	-0.44	1	1
TRF2/BLM	0.039	0.014	0.24	1	-10000	0	1
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.021	0.13	-10000	0	-1	2	2
SP1/HDAC2	0.037	0.023	-10000	0	-10000	0	0
PINX1	0.021	0.012	-10000	0	-10000	0	0
Telomerase/EST1A	0.023	0.12	-10000	0	-0.9	2	2
Smad3/Myc	0.025	0.036	0.25	9	-0.27	3	12
911 complex	0.05	0.02	0.25	1	-10000	0	1
IFNG	-0.017	0.14	-10000	0	-0.44	60	60
Telomerase/PinX1	0.016	0.12	-10000	0	-0.9	2	2
Telomerase/AKT1/mTOR/p70S6K	0.001	0.1	0.27	1	-0.42	20	21
SIN3B	0.027	0.003	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
Telomerase/EST1B	0.026	0.12	-10000	0	-0.9	2	2
response to DNA damage stimulus	0.002	0.017	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.065	0.032	-10000	0	-10000	0	0
TRF2/WRN	0.031	0.021	-10000	0	-0.24	1	1
Telomerase/hnRNP C1/C2	0.028	0.12	-10000	0	-0.9	2	2
E2F1	0.017	0.058	0.36	9	-0.45	4	13
ZNFX1	0.016	0.014	-10000	0	-10000	0	0
PIF1	0.013	0.077	-10000	0	-0.44	17	17
NCL	0.028	0.002	-10000	0	-10000	0	0
DKC1	0.027	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.004	-10000	0	-10000	0	0
mol:PIP3	0.007	0.016	-10000	0	-0.2	1	1
FRAP1	-0.011	0.11	-10000	0	-0.44	38	38
AKT1	0.002	0.036	0.17	4	-0.31	1	5
INSR	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.029	0.007	-10000	0	-10000	0	0
mol:GTP	0.03	0.042	0.23	1	-0.24	1	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.006	0.04	-10000	0	-0.22	7	7
TSC2	0.027	0.004	-10000	0	-10000	0	0
RHEB/GDP	0.02	0.03	-10000	0	-0.22	1	1
TSC1	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.024	0.015	-10000	0	-0.18	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.017	0.05	-10000	0	-0.25	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	0.007	0.076	0.22	3	-0.36	10	13
MAP3K5	0.005	0.029	0.2	4	-0.18	10	14
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
apoptosis	0.006	0.029	0.2	4	-0.18	10	14
mol:LY294002	0	0	0.001	1	-0.001	2	3
EIF4B	0.006	0.071	0.27	4	-0.34	8	12
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.026	0.069	0.22	1	-0.34	6	7
eIF4E/eIF4G1/eIF4A1	0.003	0.069	-10000	0	-0.26	35	35
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.038	0.023	-10000	0	-0.19	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.032	0.2	6	-10000	0	6
FKBP1A	0.023	0.011	-10000	0	-10000	0	0
RHEB/GTP	0.035	0.038	0.2	1	-10000	0	1
mol:Amino Acids	0	0	0.001	1	-0.001	2	3
FKBP12/Rapamycin	0.017	0.008	-10000	0	-10000	0	0
PDPK1	-0.006	0.018	0.17	1	-10000	0	1
EIF4E	0.026	0.023	-10000	0	-0.36	2	2
ASK1/PP5C	0.006	0.13	-10000	0	-0.44	43	43
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.009	0.047	-10000	0	-0.24	20	20
TSC1/TSC2	0.034	0.045	0.24	1	-0.26	1	2
tumor necrosis factor receptor activity	0	0	0.001	2	-0.001	1	3
RPS6	0.026	0.02	-10000	0	-0.44	1	1
PPP5C	0.027	0.004	-10000	0	-10000	0	0
EIF4G1	0.028	0.002	-10000	0	-10000	0	0
IRS1	0.007	0.013	-10000	0	-0.21	2	2
INS	-0.017	0.003	-10000	0	-10000	0	0
PTEN	0.026	0.006	-10000	0	-10000	0	0
PDK2	-0.006	0.02	0.17	1	-10000	0	1
EIF4EBP1	-0.067	0.3	-10000	0	-1	53	53
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
PPP2R5D	-0.008	0.11	0.25	3	-0.4	38	41
peptide biosynthetic process	-0.007	0.035	0.18	19	-0.25	1	20
RHEB	0.027	0.005	-10000	0	-10000	0	0
EIF4A1	0.023	0.011	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.002	21	-0.003	1	22
EEF2	-0.007	0.035	0.18	19	-0.25	1	20
eIF4E/4E-BP1	-0.05	0.28	-10000	0	-0.97	53	53

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.022	0.061	-10000	0	-0.18	43	43
MAPK9	0.007	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.01	0.018	-10000	0	-0.31	2	2
GNB1/GNG2	0.024	0.047	-10000	0	-0.21	23	23
GNB1	0.026	0.006	-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	0.007	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.007	0.039	-10000	0	-0.19	23	23
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	0.003	0.01	0.053	23	-10000	0	23
GNAL	0.008	0.073	-10000	0	-0.36	23	23
GNG2	0.011	0.074	-10000	0	-0.36	23	23
CRH	-0.016	0.026	-10000	0	-0.44	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.001	-10000	0	-10000	0	0
MAPK11	0.007	0.01	-10000	0	-0.16	2	2

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.081	0.1	-10000	0	-0.52	1	1
UGCG	0.019	0.061	-10000	0	-0.62	5	5
AKT1/mTOR/p70S6K/Hsp90/TERT	0.01	0.13	0.22	1	-0.45	26	27
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.019	0.06	-10000	0	-0.61	5	5
mol:DAG	-0.002	0.11	-10000	0	-0.82	11	11
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.13	0.23	1	-0.4	36	37
FRAP1	0.011	0.14	0.24	1	-0.45	39	40
FOXO3	0.017	0.11	0.3	3	-0.41	14	17
AKT1	0.018	0.11	0.25	1	-0.41	18	19
GAB2	0.028	0.004	-10000	0	-10000	0	0
SMPD1	0.014	0.084	-10000	0	-0.65	9	9
SGMS1	0.013	0.087	-10000	0	-0.61	11	11
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	0.006	0.011	-10000	0	-0.21	1	1
CALM1	0.026	0.007	-10000	0	-10000	0	0
cell proliferation	0.034	0.083	-10000	0	-0.41	10	10
EIF3A	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.042	0.016	-10000	0	-0.25	1	1
RPS6KB1	0.014	0.1	-10000	0	-0.8	9	9
mol:sphingomyelin	-0.002	0.11	-10000	0	-0.82	11	11
natural killer cell activation	0	0.002	-10000	0	-0.011	3	3
JAK3	0.028	0.019	-10000	0	-0.44	1	1
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
JAK1	0.029	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MYC	0.046	0.12	0.3	1	-0.43	5	6
MYB	0.03	0.073	-10000	0	-1.1	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.025	0.09	-10000	0	-0.4	11	11
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.042	0.1	-10000	0	-0.74	9	9
mol:PI-3-4-5-P3	0.024	0.089	-10000	0	-0.39	11	11
Rac1/GDP	0.02	0.016	-10000	0	-0.19	1	1
T cell proliferation	0.024	0.076	0.24	1	-0.4	6	7
SHC1	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.004	-10000	0	-0.066	2	2
PRKCZ	0.024	0.078	0.24	1	-0.42	6	7
NF kappa B1 p50/RelA	0.035	0.13	-10000	0	-0.42	32	32
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.025	0.053	-10000	0	-0.38	5	5
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
IL2RA	0.02	0.056	-10000	0	-0.36	13	13
IL2RB	0.019	0.058	-10000	0	-0.36	14	14
TERT	-0.014	0.14	0.36	2	-0.44	55	57
E2F1	0.032	0.044	-10000	0	-0.43	2	2
SOS1	0.028	0.002	-10000	0	-10000	0	0
RPS6	0.026	0.02	-10000	0	-0.44	1	1
mol:cAMP	-0.002	0.002	0.031	2	-10000	0	2
PTPN11	0.028	0.003	-10000	0	-10000	0	0
IL2RG	0.028	0.027	-10000	0	-0.36	3	3
actin cytoskeleton organization	0.024	0.076	0.24	1	-0.4	6	7
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL2	0.019	0.012	-10000	0	-10000	0	0
PIK3CA	0.029	0.016	-10000	0	-0.36	1	1
Rac1/GTP	0.046	0.027	-10000	0	-0.18	1	1
LCK	0.021	0.058	-10000	0	-0.42	10	10
BCL2	-0.004	0.2	-10000	0	-0.78	33	33

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.052	0.054	-10000	0	-0.19	20	20
HDAC3	0.027	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.009	0.001	-10000	0	-10000	0	0
GATA1/HDAC4	0.038	0.006	-10000	0	-10000	0	0
GATA1/HDAC5	0.037	0.014	-10000	0	-0.26	1	1
GATA2/HDAC5	0.034	0.041	-10000	0	-0.25	12	12
HDAC5/BCL6/BCoR	0.054	0.016	-10000	0	-0.21	1	1
HDAC9	-0.026	0.13	-10000	0	-0.36	80	80
Glucocorticoid receptor/Hsp90/HDAC6	0.033	0.069	-10000	0	-0.21	36	36
HDAC4/ANKRA2	0.04	0.007	-10000	0	-10000	0	0
HDAC5/YWHAB	0.023	0.023	-10000	0	-0.25	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.012	-10000	0	-0.17	2	2
GATA2	0.021	0.052	-10000	0	-0.36	11	11
HDAC4/RFXANK	0.04	0.015	-10000	0	-0.32	1	1
BCOR	0.027	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.026	0.017	-10000	0	-0.36	1	1
HDAC5	0.027	0.016	-10000	0	-0.36	1	1
GNB1/GNG2	0.026	0.056	-10000	0	-0.25	23	23
Histones	0.003	0.081	-10000	0	-0.3	13	13
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
HDAC4	0.028	0.002	-10000	0	-10000	0	0
XPO1	0.028	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.039	0.015	-10000	0	-0.25	1	1
HDAC4/Ubc9	0.04	0.007	-10000	0	-10000	0	0
HDAC7	0.028	0.002	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.034	0.019	-10000	0	-0.25	1	1
TUBA1B	0.028	0.002	-10000	0	-10000	0	0
HDAC6	0.027	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.039	0.02	-10000	0	-0.28	2	2
CAMK4	0.006	0.085	-10000	0	-0.36	31	31
Tubulin/HDAC6	0.051	0.036	-10000	0	-0.27	7	7
SUMO1	0.027	0.022	-10000	0	-0.36	2	2
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.016	0.014	-10000	0	-10000	0	0
GATA1	0.011	0.022	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
NR3C1	-0.001	0.1	-10000	0	-0.36	44	44
SUMO1/HDAC4	0.038	0.034	-10000	0	-0.26	2	2
SRF	0.027	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.024	0.02	-10000	0	-10000	0	0
Tubulin	0.036	0.038	-10000	0	-0.32	7	7
HDAC4/14-3-3 E	0.034	0.016	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
RANGAP1	0.026	0.02	-10000	0	-0.44	1	1
BCL6/BCoR	0.04	0.006	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.054	0.015	-10000	0	-0.21	1	1
HDAC4/SRF	0.038	0.06	-10000	0	-0.21	31	31
HDAC4/ER alpha	0.014	0.083	-10000	0	-0.25	55	55
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.003	0.081	-10000	0	-0.3	13	13
cell motility	0.05	0.036	-10000	0	-0.27	7	7
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
HDAC7/HDAC3	0.04	0.007	-10000	0	-10000	0	0
BCL6	0.028	0.002	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.028	0.002	-10000	0	-10000	0	0
Hsp90/HDAC6	0.038	0.011	-10000	0	-10000	0	0
ESR1	-0.009	0.11	-10000	0	-0.36	55	55
HDAC6/HDAC11	0.04	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.039	0.031	-10000	0	-10000	0	0
NPC	0.016	0	-10000	0	-10000	0	0
MEF2C	0.016	0.066	-10000	0	-0.36	18	18
RAN	0.028	0.002	-10000	0	-10000	0	0
HDAC4/MEF2C	0.07	0.048	-10000	0	-10000	0	0
GNG2	0.011	0.074	-10000	0	-0.36	23	23
NCOR2	0.027	0.016	-10000	0	-0.36	1	1
TUBB2A	0.022	0.05	-10000	0	-0.44	7	7
HDAC11	0.027	0.004	-10000	0	-10000	0	0
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
RANBP2	0.028	0	-10000	0	-10000	0	0
ANKRA2	0.027	0.005	-10000	0	-10000	0	0
RFXANK	0.027	0.019	-10000	0	-0.44	1	1
nuclear import	-0.018	0.021	0.23	1	-10000	0	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.048	0.036	-10000	0	-10000	0	0
BIRC5	0.027	0.024	0.36	1	-0.44	1	2
NFKBIA	0.005	0.011	0.25	1	-10000	0	1
CPEB1	-0.086	0.17	-10000	0	-0.36	165	165
AKT1	0.004	0.004	-10000	0	-10000	0	0
NDEL1	0.023	0.011	-10000	0	-10000	0	0
Aurora A/BRCA1	0.017	0.016	-10000	0	-10000	0	0
NDEL1/TACC3	0.054	0.038	-10000	0	-0.22	1	1
GADD45A	0.027	0.005	-10000	0	-10000	0	0
GSK3B	0.025	0.002	-10000	0	-10000	0	0
PAK1/Aurora A	0.049	0.036	-10000	0	-10000	0	0
MDM2	0.027	0.016	-10000	0	-0.36	1	1
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.011	0.027	0.27	6	-10000	0	6
TP53	0.013	0.012	-10000	0	-10000	0	0
DLG7	0.006	0.005	-10000	0	-10000	0	0
AURKAIP1	0.026	0.02	-10000	0	-0.44	1	1
ARHGEF7	0.022	0.012	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.057	0.04	-10000	0	-0.24	1	1
G2/M transition of mitotic cell cycle	0.017	0.016	-10000	0	-10000	0	0
AURKA	0.01	0.009	-10000	0	-10000	0	0
AURKB	0.009	0.009	-10000	0	-10000	0	0
CDC25B	0.013	0.049	0.29	15	-10000	0	15
G2/M transition checkpoint	0.006	0.007	-10000	0	-10000	0	0
mRNA polyadenylation	-0.027	0.074	-10000	0	-0.18	96	96
Aurora A/CPEB	-0.027	0.075	-10000	0	-0.18	96	96
Aurora A/TACC1/TRAP/chTOG	0.071	0.041	-10000	0	-10000	0	0
BRCA1	0.027	0.004	-10000	0	-10000	0	0
centrosome duplication	0.049	0.036	-10000	0	-10000	0	0
regulation of centrosome cycle	0.052	0.037	-10000	0	-0.22	1	1
spindle assembly	0.069	0.04	-10000	0	-10000	0	0
TDRD7	0.027	0.004	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.076	0.035	-10000	0	-0.22	1	1
CENPA	0.011	0.011	-10000	0	-10000	0	0
Aurora A/PP2A	0.048	0.036	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.036	0.041	0.2	2	-10000	0	2
negative regulation of DNA binding	0.012	0.016	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.031	0.021	-10000	0	-0.25	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
Ajuba/Aurora A	0.006	0.007	-10000	0	-10000	0	0
mitotic prometaphase	0.01	0.027	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.009	-10000	0	-10000	0	0
TACC1	0.024	0.01	-10000	0	-10000	0	0
TACC3	0.026	0.02	-10000	0	-0.44	1	1
Aurora A/Antizyme1	0.067	0.036	-10000	0	-0.24	1	1
Aurora A/RasGAP	0.049	0.036	-10000	0	-10000	0	0
OAZ1	0.027	0.004	-10000	0	-10000	0	0
RAN	0.028	0.002	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.025	0.003	-10000	0	-10000	0	0
GIT1	0.026	0.016	-10000	0	-0.36	1	1
GIT1/beta-PIX/PAK1	0.042	0.027	-10000	0	-0.21	1	1
Importin alpha/Importin beta/TPX2	0.011	0.027	0.27	6	-10000	0	6
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.015	0.027	0.25	6	-10000	0	6
PAK1	0.027	0.004	-10000	0	-10000	0	0
CKAP5	0.027	0.003	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.022	0.028	-10000	0	-0.2	9	9
epithelial cell differentiation	0.057	0.014	-10000	0	-10000	0	0
CYFIP2	0.027	0.016	-10000	0	-0.36	1	1
ENAH	-0.012	0.027	0.27	1	-10000	0	1
EGFR	0.024	0.023	-10000	0	-0.36	2	2
EPHA2	0.025	0.027	-10000	0	-0.44	2	2
MYO6	-0.009	0.015	0.18	3	-10000	0	3
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.054	0.015	-10000	0	-0.21	1	1
AQP5	-0.006	0.047	-10000	0	-0.51	1	1
CTNND1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.009	0.019	0.18	5	-10000	0	5
regulation of calcium-dependent cell-cell adhesion	-0.015	0.037	0.18	5	-10000	0	5
EGF	-0.06	0.16	-10000	0	-0.37	127	127
NCKAP1	0.028	0	-10000	0	-10000	0	0
AQP3	0.009	0.036	-10000	0	-0.41	2	2
cortical microtubule organization	0.057	0.014	-10000	0	-10000	0	0
GO:0000145	-0.009	0.018	0.16	5	-10000	0	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.062	0.016	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.014	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.062	0.03	-10000	0	-0.25	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.006	0.009	-10000	0	-10000	0	0
PVRL2	0.027	0.003	-10000	0	-10000	0	0
ZYX	-0.01	0.011	0.18	1	-10000	0	1
ARF6/GTP	0.065	0.035	-10000	0	-0.23	2	2
CDH1	0.028	0.003	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.003	0.09	-10000	0	-10000	0	0
RhoA/GDP	0.058	0.016	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.009	0.011	0.16	2	-10000	0	2
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
GIT1	0.026	0.016	-10000	0	-0.36	1	1
IGF1R	0.027	0.006	-10000	0	-10000	0	0
IGF1	-0.062	0.16	-10000	0	-0.36	141	141
DIAPH1	0.044	0.096	-10000	0	-0.52	12	12
Wnt receptor signaling pathway	-0.057	0.014	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.014	-10000	0	-10000	0	0
CTNNA1	0.027	0.004	-10000	0	-10000	0	0
VCL	-0.009	0.011	0.17	2	-10000	0	2
EFNA1	0.027	0.004	-10000	0	-10000	0	0
LPP	-0.01	0.019	-10000	0	-10000	0	0
Ephrin A1/EPHA2	0.047	0.023	-10000	0	-10000	0	0
SEC6/SEC8	-0.015	0.006	-10000	0	-10000	0	0
MGAT3	-0.015	0.038	0.18	5	-10000	0	5
HGF/MET	0.042	0.046	-10000	0	-0.37	1	1
HGF	0.017	0.061	-10000	0	-0.37	15	15
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.022	0.028	-10000	0	-0.2	9	9
actin cable formation	0.009	0.057	0.23	19	-0.29	1	20
KIAA1543	-0.009	0.018	0.16	5	-10000	0	5
KIFC3	-0.016	0.037	0.18	1	-10000	0	1
NCK1	0.028	0.002	-10000	0	-10000	0	0
EXOC3	0.027	0.004	-10000	0	-10000	0	0
ACTN1	-0.008	0.018	0.18	5	-10000	0	5
NCK1/GIT1	0.039	0.014	-10000	0	-0.25	1	1
mol:GDP	0.057	0.014	-10000	0	-10000	0	0
EXOC4	0.027	0.006	-10000	0	-10000	0	0
STX4	-0.009	0.013	0.18	2	-10000	0	2
PIP5K1C	-0.009	0.02	0.18	5	-10000	0	5
LIMA1	0.022	0.047	-10000	0	-0.36	9	9
ABI1	0.028	0.002	-10000	0	-10000	0	0
ROCK1	-0.008	0.039	0.29	3	-10000	0	3
adherens junction assembly	0.003	0.041	0.27	4	-10000	0	4
IGF-1R heterotetramer/IGF1	0	0.093	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.04	0.008	-10000	0	-10000	0	0
MET	0.023	0.045	0.36	1	-0.44	5	6
PLEKHA7	-0.009	0.02	0.18	5	-10000	0	5
mol:GTP	0.06	0.03	-10000	0	-0.24	2	2
establishment of epithelial cell apical/basal polarity	-0.005	0.046	0.32	3	-10000	0	3
cortical actin cytoskeleton stabilization	0.022	0.028	-10000	0	-0.2	9	9
regulation of cell-cell adhesion	-0.009	0.011	0.16	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.022	0.028	-10000	0	-0.2	9	9

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.022	0.034	-10000	0	-0.31	3	3
KLHL20	0.041	0.07	0.2	29	-0.24	8	37
CYFIP2	0.027	0.016	-10000	0	-0.36	1	1
Rac1/GDP	0.071	0.08	0.24	15	-10000	0	15
ENAH	0.021	0.035	-10000	0	-0.31	3	3
AP1M1	0.027	0.003	-10000	0	-10000	0	0
RAP1B	0.028	0.003	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.017	0.022	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.025	-10000	0	-0.16	8	8
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.052	0.05	-10000	0	-0.19	10	10
RAPGEF1	0.06	0.082	0.29	10	-10000	0	10
CTNND1	0.027	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.03	0.036	-10000	0	-0.32	3	3
CRK	0.06	0.077	-10000	0	-0.3	1	1
E-cadherin/gamma catenin/alpha catenin	0.053	0.017	-10000	0	-0.21	1	1
alphaE/beta7 Integrin	0.024	0.054	-10000	0	-0.24	23	23
IQGAP1	0.027	0.006	-10000	0	-10000	0	0
NCKAP1	0.028	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.051	0.013	-10000	0	-10000	0	0
DLG1	0.022	0.035	-10000	0	-0.31	3	3
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.004	0.01	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.022	0.077	-10000	0	-0.2	60	60
PI3K	0.008	0.015	-10000	0	-10000	0	0
ARF6	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.039	0.014	-10000	0	-0.25	1	1
TIAM1	-0.011	0.11	-10000	0	-0.36	59	59
E-cadherin(dimer)/Ca2+	0.063	0.016	-10000	0	-10000	0	0
AKT1	0.025	0.045	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
CDH1	0.028	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.084	0.083	0.26	19	-10000	0	19
actin cytoskeleton organization	0.039	0.059	0.17	35	-0.18	6	41
CDC42/GDP	0.079	0.083	0.28	16	-10000	0	16
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.02	0.01	-10000	0	-0.19	1	1
ITGB7	0.013	0.074	-10000	0	-0.36	23	23
RAC1	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.068	0.017	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.048	0.01	-10000	0	-10000	0	0
mol:GDP	0.075	0.09	0.31	13	-10000	0	13
CDC42/GTP/IQGAP1	0.034	0.015	-10000	0	-0.21	1	1
JUP	0.027	0.016	-10000	0	-0.36	1	1
p120 catenin/RhoA/GDP	0.093	0.082	0.27	19	-10000	0	19
RAC1/GTP/IQGAP1	0.033	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.04	0.013	-10000	0	-0.25	1	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
CDC42	0.025	0.017	-10000	0	-0.36	1	1
CTNNA1	0.027	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.033	0.047	0.14	40	-0.16	5	45
NME1	0.022	0.057	0.36	2	-0.44	8	10
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.021	0.034	-10000	0	-0.31	3	3
regulation of cell-cell adhesion	0.011	0.016	-10000	0	-10000	0	0
WASF2	0.015	0.026	-10000	0	-10000	0	0
Rap1/GTP	0.08	0.072	0.31	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.06	0.053	-10000	0	-10000	0	0
CCND1	0.037	0.054	0.16	39	-0.2	5	44
VAV2	0.076	0.13	0.41	1	-0.62	10	11
RAP1/GDP	0.09	0.079	0.31	10	-10000	0	10
adherens junction assembly	0.02	0.033	-10000	0	-0.3	3	3
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.028	0.002	-10000	0	-10000	0	0
PIP5K1C	0.027	0.016	-10000	0	-0.36	1	1
regulation of heterotypic cell-cell adhesion	0.046	0.047	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.014	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.014	0.027	-10000	0	-0.31	2	2
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
Rac1/GTP	-0.002	0.061	-10000	0	-0.39	8	8
E-cadherin/beta catenin/alpha catenin	0.054	0.011	-10000	0	-10000	0	0
ITGAE	0.023	0.01	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.036	-10000	0	-0.32	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.037	0.032	-10000	0	-0.25	7	7
AKT1	0.089	0.096	0.38	15	-0.38	2	17
PTK2B	0.014	0.039	-10000	0	-0.38	2	2
VEGFR2 homodimer/Frs2	0.035	0.026	-10000	0	-0.55	1	1
CAV1	0.019	0.054	-10000	0	-0.36	12	12
CALM1	0.026	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.051	0.03	0.25	2	-0.51	1	3
endothelial cell proliferation	0.098	0.13	0.28	159	-0.36	1	160
mol:Ca2+	0.013	0.018	-10000	0	-0.3	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.058	0.037	-10000	0	-0.48	1	1
RP11-342D11.1	0.011	0.025	-10000	0	-0.47	1	1
CDH5	0.028	0.002	-10000	0	-10000	0	0
VEGFA homodimer	0.064	0.024	0.26	1	-10000	0	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
SHC2	0.019	0.059	-10000	0	-0.41	11	11
HRAS/GDP	0.046	0.03	-10000	0	-0.42	1	1
SH2D2A	0.026	0.019	-10000	0	-0.44	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.097	0.084	0.28	11	-0.37	3	14
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.05	0.032	0.25	2	-0.51	1	3
VEGFR1 homodimer	0.021	0.012	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.074	0.039	-10000	0	-0.45	1	1
GRB10	0.02	0.026	-10000	0	-0.47	1	1
PTPN11	0.028	0.002	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
PAK1	0.027	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.074	0.036	-10000	0	-0.47	1	1
HRAS	0.027	0.016	-10000	0	-0.36	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.004	0.079	-10000	0	-0.39	5	5
HIF1A	0.026	0.007	-10000	0	-10000	0	0
FRS2	0.027	0.003	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.056	0.036	-10000	0	-0.48	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.025	0.031	-10000	0	-0.36	4	4
Nck/Pak	0.04	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.051	0.03	0.25	2	-0.51	1	3
mol:GDP	0.059	0.033	-10000	0	-0.44	1	1
mol:NADP	0.087	0.091	0.3	23	-0.36	3	26
eNOS/Hsp90	0.091	0.087	0.3	22	-0.36	1	23
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
mol:IP3	0.013	0.019	-10000	0	-0.3	1	1
HIF1A/ARNT	0.037	0.017	-10000	0	-0.25	1	1
SHB	0.026	0.03	0.36	1	-0.44	2	3
VEGFA	0.03	0.019	0.36	2	-10000	0	2
VEGFC	0.02	0.049	-10000	0	-0.36	10	10
FAK1/Vinculin	0.055	0.075	0.28	5	-0.54	1	6
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.062	0.041	-10000	0	-0.4	2	2
PTPN6	0.027	0.004	-10000	0	-10000	0	0
EPAS1	0.034	0.021	-10000	0	-0.33	2	2
mol:L-citrulline	0.087	0.091	0.3	23	-0.36	3	26
ITGAV	0.028	0.002	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.064	0.032	0.25	2	-0.48	1	3
VEGFR2 homodimer/VEGFA homodimer	0.053	0.032	-10000	0	-0.51	1	1
VEGFR2/3 heterodimer	0.033	0.033	-10000	0	-0.55	1	1
VEGFB	0.027	0.004	-10000	0	-10000	0	0
MAPK11	0.006	0.036	0.25	1	-0.43	2	3
VEGFR2 homodimer	0.021	0.026	-10000	0	-0.62	1	1
FLT1	0.021	0.012	-10000	0	-10000	0	0
NEDD4	0.028	0.007	-10000	0	-10000	0	0
MAPK3	0.033	0.081	0.3	7	-10000	0	7
MAPK1	0.033	0.08	0.3	7	-0.3	1	8
VEGFA145/NRP2	0.041	0.025	0.26	2	-0.25	3	5
VEGFR1/2 heterodimer	0.026	0.03	-10000	0	-0.55	1	1
KDR	0.021	0.026	-10000	0	-0.62	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.053	0.034	0.24	2	-0.47	1	3
SRC	0.017	0.014	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.047	0.087	0.3	13	-0.31	1	14
PI3K	0.055	0.058	0.3	1	-0.39	1	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.051	0.03	0.25	2	-0.51	1	3
FES	0.021	0.027	-10000	0	-0.48	1	1
GAB1	0.028	0.036	-10000	0	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.032	0.032	0.25	1	-0.33	1	2
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
SOS1	0.028	0.002	-10000	0	-10000	0	0
ARNT	0.027	0.016	-10000	0	-0.36	1	1
eNOS/Caveolin-1	0.086	0.083	0.29	10	-0.35	2	12
VEGFR2 homodimer/VEGFA homodimer/Yes	0.042	0.038	0.25	1	-0.67	1	2
PI3K/GAB1	0.053	0.055	0.27	1	-0.42	1	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.076	0.034	-10000	0	-0.47	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.042	0.046	-10000	0	-0.43	2	2
HSP90AA1	0.026	0.007	-10000	0	-10000	0	0
CDC42	0.021	0.026	-10000	0	-0.48	1	1
actin cytoskeleton reorganization	0.049	0.032	0.24	2	-0.5	1	3
PTK2	0.028	0.054	0.26	4	-0.57	1	5
EDG1	0.011	0.025	-10000	0	-0.47	1	1
mol:DAG	0.013	0.019	-10000	0	-0.3	1	1
CaM/Ca2+	0.022	0.026	-10000	0	-10000	0	0
MAP2K3	0.012	0.034	-10000	0	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.064	0.056	-10000	0	-0.48	1	1
PLCG1	0.013	0.019	-10000	0	-0.31	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.039	0.041	-10000	0	-0.31	1	1
IQGAP1	0.027	0.006	-10000	0	-10000	0	0
YES1	0.022	0.019	-10000	0	-0.36	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.051	0.03	0.25	2	-0.51	1	3
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.05	0.029	0.25	1	-0.51	1	2
cell migration	0.06	0.078	0.29	10	-0.48	1	11
mol:PI-3-4-5-P3	0.054	0.056	0.29	1	-0.36	1	2
FYN	0.027	0.005	-10000	0	-10000	0	0
VEGFB/NRP1	0.027	0.026	-10000	0	-0.45	1	1
mol:NO	0.087	0.091	0.3	23	-0.36	3	26
PXN	0.028	0.002	-10000	0	-10000	0	0
HRAS/GTP	0.027	0.024	-10000	0	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.04	0.031	-10000	0	-0.48	1	1
VHL	0.027	0.004	-10000	0	-10000	0	0
ITGB3	0.023	0.041	-10000	0	-0.36	7	7
NOS3	0.09	0.094	0.32	21	-0.4	3	24
VEGFR2 homodimer/VEGFA homodimer/Sck	0.046	0.046	0.25	1	-0.51	1	2
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.007	0.02	-10000	0	-10000	0	0
PRKCB	-0.01	0.052	-10000	0	-10000	0	0
VCL	0.027	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1	0.03	0.028	0.23	2	-0.47	1	3
VEGFR1/2 heterodimer/VEGFA homodimer	0.038	0.035	0.25	1	-0.51	1	2
VEGFA165/NRP2	0.041	0.025	0.26	2	-0.25	3	5
MAPKKK cascade	0.033	0.037	-10000	0	-0.42	1	1
NRP2	0.026	0.027	-10000	0	-0.36	3	3
VEGFC homodimer	0.02	0.049	-10000	0	-0.36	10	10
NCK1	0.028	0.002	-10000	0	-10000	0	0
ROCK1	0.022	0.019	-10000	0	-0.36	1	1
FAK1/Paxillin	0.055	0.075	0.28	5	-0.54	1	6
MAP3K13	0.022	0.028	-10000	0	-0.48	1	1
PDPK1	0.078	0.087	0.25	85	-0.34	1	86

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.024	0.035	0.36	5	-10000	0	5
PI3K Class IB/PDE3B	0.024	0.035	-10000	0	-0.36	5	5
PDE3B	0.024	0.035	-10000	0	-0.36	5	5

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.058	0.07	0.15	177	-0.29	1	178
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.011	0.035	0.15	11	-0.17	2	13
AP2	0.04	0.013	-10000	0	-0.25	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.033	0.013	-10000	0	-10000	0	0
CLTB	0.027	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.006	-10000	0	-10000	0	0
CD4	0.016	0.064	-10000	0	-0.36	17	17
CLTA	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
ARFGAP1	0.005	0.018	0.26	2	-0.25	1	3
mol:PI-4-5-P2	0.006	0.007	-10000	0	-10000	0	0
ARF1/GTP	0.036	0.01	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.007	0.015	0.18	2	-0.23	1	3
mol:Choline	0.006	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.006	-10000	0	-10000	0	0
DDEF1	0.005	0.007	-10000	0	-10000	0	0
ARF1/GDP	0.002	0.016	0.18	2	-0.21	1	3
AP2M1	0.028	0.002	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.012	0.006	-10000	0	-10000	0	0
Rac/GTP	0.02	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0.024	0.19	2	-0.18	1	3
ARFIP2	0.017	0.021	-10000	0	-10000	0	0
COPA	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.014	0.018	0.14	1	-10000	0	1
ARF1/GTP/ARHGAP10	0.02	0.006	-10000	0	-10000	0	0
GGA3	0.027	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.025	0.027	-10000	0	-0.24	5	5
AP2A1	0.027	0.016	-10000	0	-0.36	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.009	0.019	0.13	2	-0.21	1	3
ARF1/GDP/Membrin	0.018	0.034	-10000	0	-0.27	6	6
Arfaptin 2/Rac/GDP	0.032	0.012	-10000	0	-10000	0	0
CYTH2	0.029	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.038	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.019	0.006	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.019	0.034	-10000	0	-10000	0	0
PLD2	0.006	0.007	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.005	0.018	0.26	2	-0.25	1	3
PIP5K1A	0.006	0.007	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.013	0.027	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.005	0.007	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.005	0.018	0.26	2	-0.25	1	3
GOSR2	0.012	0.007	-10000	0	-10000	0	0
USO1	0.01	0.023	-10000	0	-0.31	3	3
GBF1	0.007	0.037	-10000	0	-0.31	8	8
ARF1/GTP/Arfaptin 2	0.037	0.009	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.046	0.047	-10000	0	-0.21	18	18

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.024	0.035	-9999	-0.36	5	5
positive regulation of NF-kappaB transcription factor activity	0.028	0.031	-9999	-0.25	5	5
MAP2K4	0.017	0.026	-9999	-10000	0	0
IKBKB	0.024	0.009	-9999	-10000	0	0
TNFRSF10B	0.021	0.012	-9999	-10000	0	0
TNFRSF10A	0.021	0.012	-9999	-10000	0	0
SMPD1	0.007	0.037	-9999	-0.36	5	5
IKBKG	0.027	0.016	-9999	-0.36	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.021	0.012	-9999	-10000	0	0
TRAIL/TRAILR2	0.029	0.031	-9999	-0.25	5	5
TRAIL/TRAILR3	0.005	0.091	-9999	-0.31	46	46
TRAIL/TRAILR1	0.029	0.031	-9999	-0.25	5	5
TRAIL/TRAILR4	0.029	0.031	-9999	-0.25	5	5
TRAIL/TRAILR1/DAP3/GTP	0.037	0.031	-9999	-0.19	5	5
IKK complex	0.019	0.042	-9999	-0.33	2	2
RIPK1	0.027	0.004	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.02	0.003	-9999	-10000	0	0
MAPK3	0.011	0.024	-9999	-0.25	5	5
MAP3K1	0.02	0.029	-9999	-10000	0	0
TRAILR4 (trimer)	0.021	0.012	-9999	-10000	0	0
TRADD	0.028	0.003	-9999	-10000	0	0
TRAILR1 (trimer)	0.021	0.012	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.021	0.024	-9999	-10000	0	0
CFLAR	0.028	0	-9999	-10000	0	0
MAPK1	0.011	0.022	-9999	-0.25	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP	0.059	0.042	-9999	-10000	0	0
mol:ceramide	0.007	0.037	-9999	-0.36	5	5
FADD	0.027	0.004	-9999	-10000	0	0
MAPK8	0.014	0.03	-9999	-10000	0	0
TRAF2	0.027	0.016	-9999	-0.36	1	1
TRAILR3 (trimer)	-0.01	0.12	-9999	-0.44	41	41
CHUK	0.027	0.006	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0.04	0.034	-9999	-0.21	5	5
DAP3	0.027	0.004	-9999	-10000	0	0
CASP10	0.005	0.025	-9999	-0.24	5	5
JNK cascade	0.028	0.031	-9999	-0.25	5	5
TRAIL (trimer)	0.024	0.035	-9999	-0.36	5	5
TNFRSF10C	-0.011	0.12	-9999	-0.44	41	41
TRAIL/TRAILR1/DAP3/GTP/FADD	0.046	0.036	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	0.04	0.034	-9999	-0.21	5	5
cell death	0.007	0.037	-9999	-0.36	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.021	0.024	-9999	-10000	0	0
TRAILR2 (trimer)	0.021	0.012	-9999	-10000	0	0
CASP8	0.015	0.023	-9999	-0.47	1	1
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.059	0.042	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.027	0.006	-9999	-10000	0	0
Rac1/GDP	0.026	0.011	-9999	-10000	0	0
DOCK1	0.026	0.016	-9999	-0.36	1	1
ITGA4	0.014	0.072	-9999	-0.36	22	22
RAC1	0.025	0.008	-9999	-10000	0	0
alpha4/beta7 Integrin	0.02	0.081	-9999	-0.28	40	40
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.023	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin	0.046	0.05	-9999	-0.21	22	22
alpha4/beta7 Integrin/Paxillin	0.029	0.066	-9999	-0.36	5	5
lamellipodium assembly	0.008	0.081	-9999	-0.4	16	16
PIK3CA	0.027	0.016	-9999	-0.36	1	1
PI3K	0.039	0.015	-9999	-0.25	1	1
ARF6	0.026	0.007	-9999	-10000	0	0
TLN1	0.027	0.004	-9999	-10000	0	0
PXN	0.013	0.002	-9999	-10000	0	0
PIK3R1	0.027	0.006	-9999	-10000	0	0
ARF6/GTP	0.047	0.044	-9999	-10000	0	0
cell adhesion	0.049	0.046	-9999	-10000	0	0
CRKL/CBL	0.039	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.037	0.045	-9999	-10000	0	0
ITGB1	0.028	0.002	-9999	-10000	0	0
ITGB7	0.013	0.074	-9999	-0.36	23	23
ARF6/GDP	0.026	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.046	0.064	-9999	-0.35	9	9
p130Cas/Crk/Dock1	0.045	0.027	-9999	-0.21	2	2
VCAM1	0.019	0.056	-9999	-0.36	13	13
alpha4/beta1 Integrin/Paxillin/Talin	0.051	0.047	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.051	0.045	-9999	-10000	0	0
BCAR1	0.027	0.016	-9999	-0.36	1	1
mol:GDP	-0.049	0.045	-9999	-10000	0	0
CBL	0.027	0.004	-9999	-10000	0	0
PRKACA	0.027	0.003	-9999	-10000	0	0
GIT1	0.026	0.016	-9999	-0.36	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.051	0.047	-9999	-10000	0	0
Rac1/GTP	0.006	0.088	-9999	-0.45	16	16

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.048	0.052	-10000	0	-0.22	4	4
TC10/GTP	0.033	0.049	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.077	0.026	-10000	0	-10000	0	0
HRAS	0.027	0.016	-10000	0	-0.36	1	1
APS homodimer	0.02	0.058	0.36	1	-0.44	9	10
GRB14	-0.005	0.1	-10000	0	-0.39	42	42
FOXO3	-0.01	0.15	-10000	0	-0.57	38	38
AKT1	-0.002	0.06	0.21	3	-10000	0	3
INSR	0.039	0.014	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.078	0.072	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.025	0.008	-10000	0	-10000	0	0
SORBS1	0.017	0.06	-10000	0	-0.36	15	15
CRK	0.023	0.01	-10000	0	-10000	0	0
PTPN1	0.006	0.022	-10000	0	-10000	0	0
CAV1	0.012	0.046	0.18	10	-10000	0	10
CBL/APS/CAP/Crk-II/C3G	0.054	0.061	0.26	1	-0.23	6	7
Insulin Receptor/Insulin/IRS1/NCK2	0.077	0.026	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.059	0.025	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.063	0.068	-10000	0	-0.3	5	5
RPS6KB1	-0.007	0.054	0.19	3	-10000	0	3
PARD6A	0.026	0.027	-10000	0	-0.44	2	2
CBL	0.027	0.004	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.019	0.008	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.031	0.057	-10000	0	-10000	0	0
HRAS/GTP	0.022	0.013	-10000	0	-10000	0	0
Insulin Receptor	0.039	0.014	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.085	0.032	-10000	0	-10000	0	0
PRKCI	0.027	0.055	-10000	0	-0.4	4	4
Insulin Receptor/Insulin/GRB14/PDK1	0.022	0.055	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.043	0.028	-10000	0	-0.35	1	1
PI3K	0.071	0.029	-10000	0	-10000	0	0
NCK2	0.028	0.001	-10000	0	-10000	0	0
RHOQ	0.028	0.002	-10000	0	-10000	0	0
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.011	-10000	0	-0.25	1	1
AKT2	-0.003	0.059	0.21	1	-10000	0	1
PRKCZ	0.017	0.077	-10000	0	-0.4	4	4
SH2B2	0.02	0.058	0.36	1	-0.44	9	10
SHC/SHIP	0.044	0.03	0.19	4	-10000	0	4
F2RL2	0.002	0.1	-10000	0	-0.43	33	33
TRIP10	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.059	0.024	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.037	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.084	0.032	-10000	0	-10000	0	0
RAPGEF1	0.027	0.016	-10000	0	-0.36	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.028	0.002	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.046	0.058	0.26	1	-0.24	9	10
TC10/GDP	0.02	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.068	0.034	-10000	0	-10000	0	0
INPP5D	0.016	0.041	0.18	10	-10000	0	10
SOS1	0.028	0.002	-10000	0	-10000	0	0
SGK1	-0.026	0.18	-10000	0	-0.74	35	35
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.028	0.002	-10000	0	-10000	0	0
IRS1	0.028	0.002	-10000	0	-10000	0	0
p62DOK/RasGAP	0.044	0.029	-10000	0	-0.35	1	1
INS	0.028	0.014	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.016	0.041	0.18	10	-10000	0	10
GRB2	0.027	0.004	-10000	0	-10000	0	0
EIF4EBP1	-0.007	0.054	0.23	4	-10000	0	4
PTPRA	0.029	0.016	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
TC10/GTP/CIP4	0.037	0.006	-10000	0	-10000	0	0
PDPK1	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.036	0.019	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.06	0.023	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.051	0.025	-10000	0	-10000	0	0
Par3/Par6	0.046	0.068	-10000	0	-0.23	31	31

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.021	0.009	-10000	0	-10000	0	0
TRAF2/ASK1	0.036	0.013	-10000	0	-0.21	1	1
ATM	0.027	0.005	-10000	0	-10000	0	0
MAP2K3	0.008	0.074	0.3	2	-0.32	11	13
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.016	0.063	0.26	4	-0.34	6	10
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.023	0.047	0.36	1	-0.43	6	7
TXN	0.007	0.001	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
GADD45A	0.027	0.005	-10000	0	-10000	0	0
GADD45B	0.027	0.004	-10000	0	-10000	0	0
MAP3K1	0.026	0.016	-10000	0	-0.36	1	1
MAP3K6	0.025	0.017	-10000	0	-0.36	1	1
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
MAP3K4	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.037	0.017	-10000	0	-0.25	1	1
TAK1/TAB family	0	0.014	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.047	0.02	-10000	0	-0.19	1	1
TRAF2	0.027	0.016	-10000	0	-0.36	1	1
RAC1/OSM/MEKK3/MKK3	0.019	0.064	-10000	0	-0.3	5	5
TRAF6	0.007	0.001	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.013	0.11	0.36	1	-0.37	50	51
CCM2	0.025	0.017	-10000	0	-0.36	1	1
CaM/Ca2+/CAMKIIB	0.011	0.069	0.23	1	-0.22	50	51
MAPK11	0.025	0.027	-10000	0	-0.44	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.025	0.069	0.24	1	-0.2	45	46
OSM/MEKK3	0.036	0.018	-10000	0	-0.25	1	1
TAOK1	0.014	0.004	-10000	0	-10000	0	0
TAOK2	0.014	0.003	-10000	0	-10000	0	0
TAOK3	0.014	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.027	0.004	-10000	0	-10000	0	0
MAP3K10	0.028	0.014	0.36	1	-10000	0	1
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.025	0.009	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.058	0.034	0.24	1	-0.23	5	6

×

PLK2 and PLK4 events

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
PLK2	0.023	0.042	-9999	-0.44	5	5
PLK4	0.027	0.005	-9999	-10000	0	0
regulation of centriole replication	0.01	0.03	-9999	-0.32	5	5

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.028	0.004	-10000	0	-10000	0	0
ELF1	0.021	0.042	-10000	0	-0.31	9	9
CCNA2	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
JAK3	0.027	0.019	-10000	0	-0.44	1	1
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
JAK1	0.027	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.042	0.086	-10000	0	-0.46	7	7
SHC1	0.028	0.004	-10000	0	-10000	0	0
SP1	0.03	0.036	-10000	0	-0.3	7	7
IL2RA	0.006	0.078	-10000	0	-0.63	9	9
IL2RB	0.018	0.058	-10000	0	-0.36	14	14
SOS1	0.028	0.002	-10000	0	-10000	0	0
IL2RG	0.026	0.027	-10000	0	-0.36	3	3
G1/S transition of mitotic cell cycle	0.024	0.084	0.4	2	-0.59	6	8
PTPN11	0.028	0.002	-10000	0	-10000	0	0
CCND2	0.013	0.058	-10000	0	-0.63	5	5
LCK	0.02	0.058	-10000	0	-0.43	10	10
GRB2	0.028	0.004	-10000	0	-10000	0	0
IL2	0.019	0.01	-10000	0	-10000	0	0
CDK6	0.026	0.006	-10000	0	-10000	0	0
CCND3	0.041	0.085	0.34	4	-0.5	3	7

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.029	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.05	0.077	0.23	27	-0.27	1	28
ERC1	0.027	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.058	-10000	0	-0.31	16	16
NFKBIA	0.012	0.01	-10000	0	-10000	0	0
BIRC2	0.026	0.016	-10000	0	-0.36	1	1
IKBKB	0.024	0.009	-10000	0	-10000	0	0
RIPK2	0.024	0.01	-10000	0	-10000	0	0
IKBKG	0.025	0.044	-10000	0	-0.33	4	4
IKK complex/A20	0.053	0.061	-10000	0	-0.33	1	1
NEMO/A20/RIP2	0.024	0.01	-10000	0	-10000	0	0
XPO1	0.028	0	-10000	0	-10000	0	0
NEMO/ATM	0.045	0.055	0.27	2	-0.32	5	7
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.028	0.002	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.037	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.043	0.051	-10000	0	-0.31	2	2
BCL10/MALT1/TRAF6	0.04	0.029	-10000	0	-0.21	2	2
NOD2	0.014	0.077	-10000	0	-0.44	17	17
NFKB1	0.029	0.005	-10000	0	-10000	0	0
RELA	0.029	0.005	-10000	0	-10000	0	0
MALT1	0.02	0.02	-10000	0	-0.36	1	1
cIAP1/UbcH5C	0.039	0.015	-10000	0	-0.25	1	1
ATM	0.027	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	0.037	0.027	-10000	0	-0.25	5	5
TRAF6	0.027	0.003	-10000	0	-10000	0	0
PRKCA	0.027	0.005	-10000	0	-10000	0	0
CHUK	0.027	0.006	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
TNF	0.024	0.035	-10000	0	-0.36	5	5
NF kappa B1 p50/RelA	0.06	0.016	-10000	0	-10000	0	0
BCL10	0.026	0.016	-10000	0	-0.36	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.01	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.029	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
IKK complex	0.047	0.054	-10000	0	-0.33	2	2
CYLD	0.027	0.016	-10000	0	-0.36	1	1
IKK complex/PKC alpha	0.053	0.057	-10000	0	-0.32	2	2

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.058	0.049	-10000	0	-0.39	1	1
Ran/GTP/Exportin 1/HDAC1	-0.008	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.031	0.057	-10000	0	-0.34	3	3
SUMO1	0.027	0.022	-10000	0	-0.36	2	2
ZFPM1	0.018	0.065	-10000	0	-0.44	12	12
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.012	-10000	0	-0.17	2	2
FKBP3	0.025	0.017	-10000	0	-0.36	1	1
Histones	0.061	0.038	-10000	0	-10000	0	0
YY1/LSF	0.01	0.068	-10000	0	-0.31	6	6
SMG5	0.027	0.004	-10000	0	-10000	0	0
RAN	0.028	0.002	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.024	0.022	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.026	0.047	-10000	0	-10000	0	0
SAP18	0.022	0.012	-10000	0	-10000	0	0
RELA	0.023	0.033	-10000	0	-0.51	1	1
HDAC1/Smad7	0.039	0.028	-10000	0	-0.21	1	1
RANGAP1	0.026	0.02	-10000	0	-0.44	1	1
HDAC3/TR2	0.035	0.033	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.019	0.043	-10000	0	-0.33	1	1
NF kappa B1 p50/RelA	0.028	0.061	0.23	3	-0.31	7	10
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.021	0.052	-10000	0	-0.36	11	11
GATA1	0.011	0.022	-10000	0	-10000	0	0
Mad/Max	0.037	0.02	-10000	0	-0.25	2	2
NuRD/MBD3 Complex/GATA1/Fog1	0.013	0.066	-10000	0	-0.31	5	5
RBBP7	0.027	0.004	-10000	0	-10000	0	0
NPC	0.016	0	-10000	0	-10000	0	0
RBBP4	0.027	0.005	-10000	0	-10000	0	0
MAX	0.026	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.027	0.004	-10000	0	-10000	0	0
NFKBIA	0.021	0.017	-10000	0	-10000	0	0
KAT2B	0.011	0.078	-10000	0	-0.36	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.021	0.014	-10000	0	-10000	0	0
SIN3 complex	0.051	0.033	-10000	0	-10000	0	0
SMURF1	0.026	0.006	-10000	0	-10000	0	0
CHD3	0.023	0.011	-10000	0	-10000	0	0
SAP30	0.027	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.023	0.011	-10000	0	-10000	0	0
YY1/HDAC3	0.012	0.058	-10000	0	-0.29	5	5
YY1/HDAC2	0.011	0.067	-10000	0	-0.31	6	6
YY1/HDAC1	0.011	0.066	-10000	0	-0.31	6	6
NuRD/MBD2 Complex (MeCP1)	0.016	0.039	-10000	0	-0.33	1	1
PPARG	0.021	0.036	-10000	0	-0.23	7	7
HDAC8/hEST1B	0.054	0.011	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.035	0.034	-10000	0	-10000	0	0
MBD3L2	-0.018	0.003	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.027	-10000	0	-0.21	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.013	0.069	-10000	0	-0.31	9	9
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.022	0.016	-10000	0	-10000	0	0
HDAC2	0.027	0.005	-10000	0	-10000	0	0
YY1	0.01	0.044	-10000	0	-0.22	21	21
HDAC8	0.028	0.002	-10000	0	-10000	0	0
SMAD7	0.02	0.02	-10000	0	-0.36	1	1
NCOR2	0.027	0.016	-10000	0	-0.36	1	1
MXD1	0.026	0.022	-10000	0	-0.36	2	2
STAT3	0.021	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.028	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.024	0.068	-10000	0	-0.29	6	6
YY1/SAP30/HDAC1	0.025	0.066	-10000	0	-0.29	6	6
EP300	0.026	0.006	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.021	0.006	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.017	-10000	0	-10000	0	0
histone deacetylation	0.014	0.046	-10000	0	-0.4	3	3
STAT3 (dimer non-phopshorylated)/HDAC3	0.03	0.022	-10000	0	-10000	0	0
nuclear export	-0.054	0.011	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GATAD2B	0.027	0.004	-10000	0	-10000	0	0
GATAD2A	0.027	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.031	0.044	-10000	0	-0.3	1	1
GATA1/HDAC1	0.037	0.009	-10000	0	-10000	0	0
GATA1/HDAC3	0.033	0.032	-10000	0	-10000	0	0
CHD4	0.027	0.004	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.037	0.027	-10000	0	-0.25	5	5
SIN3/HDAC complex/Mad/Max	0.033	0.046	-10000	0	-0.33	2	2
NuRD Complex	-0.007	0.091	-10000	0	-0.3	24	24
positive regulation of chromatin silencing	0.058	0.037	-10000	0	-10000	0	0
SIN3B	0.027	0.003	-10000	0	-10000	0	0
MTA2	0.027	0.004	-10000	0	-10000	0	0
SIN3A	0.027	0.006	-10000	0	-10000	0	0
XPO1	0.028	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.038	0.031	-10000	0	-0.26	2	2
HDAC complex	0.066	0.02	-10000	0	-10000	0	0
GATA1/Fog1	0.031	0.05	-10000	0	-0.32	12	12
FKBP25/HDAC1/HDAC2	0.049	0.021	-10000	0	-0.21	1	1
TNF	0.024	0.035	-10000	0	-0.36	5	5
negative regulation of cell growth	0.033	0.046	-10000	0	-0.32	2	2
NuRD/MBD2/PRMT5 Complex	0.016	0.039	-10000	0	-0.33	1	1
Ran/GTP/Exportin 1	0.039	0.031	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.018	0.047	-10000	0	-0.36	3	3
SIN3/HDAC complex/NCoR1	0.01	0.052	-10000	0	-0.31	10	10
TFCP2	0.027	0.016	-10000	0	-0.36	1	1
NR2C1	0.028	0.002	-10000	0	-10000	0	0
MBD3	0.026	0.025	-10000	0	-0.4	2	2
MBD2	0.02	0.012	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.053	0.015	-10000	0	-10000	0	0
CLOCK	0.029	0.006	-10000	0	-10000	0	0
TIMELESS/CRY2	0.039	0.013	-10000	0	-10000	0	0
DEC1/BMAL1	0.03	0.05	-10000	0	-0.33	11	11
ATR	0.028	0.002	-10000	0	-10000	0	0
NR1D1	0.023	0.01	-10000	0	-10000	0	0
ARNTL	0.03	0.004	-10000	0	-10000	0	0
TIMELESS	0.023	0.009	-10000	0	-10000	0	0
NPAS2	0.03	0.003	-10000	0	-10000	0	0
CRY2	0.027	0.003	-10000	0	-10000	0	0
mol:CO	-0.009	0.003	0.069	1	-10000	0	1
CHEK1	0.027	0.004	-10000	0	-10000	0	0
mol:HEME	0.009	0.003	-10000	0	-0.069	1	1
PER1	0.022	0.019	-10000	0	-0.36	1	1
BMAL/CLOCK/NPAS2	0.065	0.014	-10000	0	-10000	0	0
BMAL1/CLOCK	0.024	0.045	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.053	0.015	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.054	0.015	-10000	0	-10000	0	0
mol:NADPH	0.009	0.003	-10000	0	-0.069	1	1
PER1/TIMELESS	0.033	0.019	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.01	0.065	-10000	0	-0.46	11	11

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.027	0.004	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.041	0.028	-9999	-0.19	4	4
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.01	0.015	-9999	-0.3	1	1
AURKB	0.023	0.011	-9999	-10000	0	0
AURKC	0.023	0.033	-9999	-0.36	4	4

×

Atypical NF-kappaB 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
BCL3/RelA	0.04	0.008	-10000	0	-10000	0	0
FBXW11	0.027	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.026	0.011	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.054	0.055	0.21	6	-10000	0	6
NFKBIA	0.047	0.055	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.026	0.011	-10000	0	-10000	0	0
ARRB2	0.012	0.006	-10000	0	-10000	0	0
REL	0.028	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.011	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.026	0.011	-10000	0	-10000	0	0
PIK3CA	0.027	0.016	-10000	0	-0.36	1	1
NF kappa B1 p50 dimer	0.019	0.008	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
NFKB1	0.012	0.005	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.038	0.045	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.046	0.054	0.2	5	-10000	0	5
SRC	0.017	0.014	-10000	0	-10000	0	0
PI3K	0.039	0.015	-10000	0	-0.25	1	1
NF kappa B1 p50/RelA	0.038	0.045	-10000	0	-10000	0	0
IKBKB	0.024	0.009	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.004	-10000	0	-10000	0	0
SYK	0.027	0.004	-10000	0	-10000	0	0
I kappa B alpha/PIK3R1	0.057	0.059	0.22	7	-10000	0	7
cell death	0.044	0.053	0.19	5	-10000	0	5
NF kappa B1 p105/c-Rel	0.026	0.011	-10000	0	-10000	0	0
LCK	0.019	0.058	-10000	0	-0.43	10	10
BCL3	0.027	0.003	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.01	0.023	-10000	0	-0.25	1	1
adherens junction organization	0.036	0.039	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.027	-10000	0	-10000	0	0
FMN1	0.038	0.037	-10000	0	-10000	0	0
mol:IP3	0.011	0.02	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.043	0.036	-10000	0	-0.21	1	1
CTNNB1	0.028	0.004	-10000	0	-10000	0	0
AKT1	0.051	0.049	0.18	8	-10000	0	8
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.065	0.063	0.22	2	-0.48	1	3
CTNND1	0.03	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.039	0.037	-10000	0	-10000	0	0
VASP	0.039	0.037	-10000	0	-10000	0	0
ZYX	0.037	0.036	-10000	0	-10000	0	0
JUB	0.039	0.035	0.15	2	-0.2	1	3
EGFR(dimer)	0.05	0.043	-10000	0	-10000	0	0
E-cadherin/beta catenin-gamma catenin	0.051	0.015	-10000	0	-0.2	1	1
mol:PI-3-4-5-P3	0.084	0.061	0.21	9	-10000	0	9
PIK3CA	0.03	0.017	-10000	0	-0.36	1	1
PI3K	0.086	0.063	0.22	9	-10000	0	9
FYN	-0.003	0.044	-10000	0	-10000	0	0
mol:Ca2+	0.011	0.019	-10000	0	-10000	0	0
JUP	0.027	0.016	-10000	0	-0.36	1	1
PIK3R1	0.03	0.008	-10000	0	-10000	0	0
mol:DAG	0.011	0.02	-10000	0	-10000	0	0
CDH1	0.028	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.033	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.038	0.036	-10000	0	-10000	0	0
SRC	0.017	0.014	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
EGFR	0.024	0.023	-10000	0	-0.36	2	2
CASR	-0.006	0.044	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.025	-10000	0	-10000	0	0
AKT2	0.054	0.049	0.18	6	-10000	0	6
actin cable formation	0.033	0.036	0.18	1	-10000	0	1
apoptosis	-0.047	0.05	0.24	1	-0.19	7	8
CTNNA1	0.03	0.006	-10000	0	-10000	0	0
mol:GDP	0.008	0.02	-10000	0	-10000	0	0
PIP5K1A	0.039	0.037	-10000	0	-10000	0	0
PLCG1	0.011	0.02	-10000	0	-10000	0	0
Rac1/GTP	0.055	0.043	-10000	0	-10000	0	0
homophilic cell adhesion	0.002	0.004	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.02	0.013	-10000	0	-10000	0	0
SMAD2	0.013	0.032	0.17	1	-0.2	1	2
SMAD3	0.019	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4	0.024	0.061	-10000	0	-0.42	10	10
SMAD4/Ubc9/PIASy	0.04	0.026	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.039	0.045	-10000	0	-10000	0	0
PPM1A	0.026	0.007	-10000	0	-10000	0	0
CALM1	0.026	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	0.015	0.023	-10000	0	-10000	0	0
MAP3K1	0.026	0.016	-10000	0	-0.36	1	1
TRAP-1/SMAD4	0.029	0.022	-10000	0	-0.25	1	1
MAPK3	0.027	0.016	-10000	0	-0.36	1	1
MAPK1	0.026	0.006	-10000	0	-10000	0	0
NUP214	0.027	0.004	-10000	0	-10000	0	0
CTDSP1	0.028	0.001	-10000	0	-10000	0	0
CTDSP2	0.028	0.002	-10000	0	-10000	0	0
CTDSPL	0.027	0.003	-10000	0	-10000	0	0
KPNB1	0.027	0.004	-10000	0	-10000	0	0
TGFBRAP1	0.027	0.016	-10000	0	-0.36	1	1
UBE2I	0.027	0.004	-10000	0	-10000	0	0
NUP153	0.027	0.004	-10000	0	-10000	0	0
KPNA2	0.028	0.014	0.36	1	-10000	0	1
PIAS4	0.027	0.004	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.024	0.02	-10000	0	-10000	0	0
ATM	0.027	0.005	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
PRKDC	0.025	0.016	0.36	1	-10000	0	1
ATR	0.028	0.002	-10000	0	-10000	0	0
UBE2L3	0.027	0.006	-10000	0	-10000	0	0
FANCD2	0.021	0.012	-10000	0	-0.26	1	1
protein ubiquitination	0.071	0.027	0.24	3	-0.23	1	4
XRCC5	0.028	0.001	-10000	0	-10000	0	0
XRCC6	0.026	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.046	0.024	-10000	0	-10000	0	0
MRE11A	0.027	0.004	-10000	0	-10000	0	0
DNA-PK	0.048	0.022	0.25	1	-10000	0	1
FA complex/FANCD2/Ubiquitin	0.03	0.043	-10000	0	-0.39	4	4
FANCF	0.027	0.003	-10000	0	-10000	0	0
BRCA1	0.027	0.004	-10000	0	-10000	0	0
CCNE1	0.027	0.036	0.36	3	-0.44	2	5
CDK2/Cyclin E1	0.04	0.026	0.26	3	-0.32	2	5
FANCG	0.028	0.014	0.36	1	-10000	0	1
BRCA1/BACH1/BARD1	0.041	0.005	-10000	0	-10000	0	0
FANCE	0.027	0.003	-10000	0	-10000	0	0
FANCC	0.027	0.004	-10000	0	-10000	0	0
NBN	0.023	0.018	-10000	0	-0.36	1	1
FANCA	0.027	0.004	-10000	0	-10000	0	0
DNA repair	0.042	0.063	0.24	10	-10000	0	10
BRCA1/BARD1/ubiquitin	0.041	0.005	-10000	0	-10000	0	0
BARD1/DNA-PK	0.061	0.027	0.26	1	-10000	0	1
FANCL	0.028	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.024	0.02	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.024	0.044	-10000	0	-0.26	6	6
BRCA1/BACH1/BARD1/TopBP1	0.055	0.009	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.058	0.028	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.033	0.028	-10000	0	-10000	0	0
BRCA1/BACH1	0.027	0.004	-10000	0	-10000	0	0
BARD1	0.028	0.001	-10000	0	-10000	0	0
PCNA	0.023	0.011	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.054	0.012	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.053	0.013	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.054	0.031	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	0.061	0.038	0.26	1	-10000	0	1
BRCA1/BARD1/Ubiquitin	0.041	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.036	0.022	-10000	0	-10000	0	0
FA complex	0.03	0.017	0.17	1	-10000	0	1
BARD1/EWS	0.039	0.009	-10000	0	-10000	0	0
RBBP8	0.01	0.012	-10000	0	-0.25	1	1
TP53	0.023	0.011	-10000	0	-10000	0	0
TOPBP1	0.028	0.002	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.056	0.027	-10000	0	-10000	0	0
BRCA1/BARD1	0.078	0.029	0.25	3	-0.23	1	4
CSTF1	0.016	0.014	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.021	0.001	-10000	0	-10000	0	0
CDK2	0.028	0.002	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.026	0.007	-10000	0	-10000	0	0
RAD50	0.027	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.041	0.005	-10000	0	-10000	0	0
EWSR1	0.027	0.006	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.006	0.01	-9999	-10000	0	0
MDM2/SUMO1	0.038	0.036	-9999	-0.33	2	2
HDAC4	0.028	0.002	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.006	0.009	-9999	-10000	0	0
SUMO1	0.027	0.022	-9999	-0.36	2	2
NPC/RanGAP1/SUMO1	0.012	0.012	-9999	-0.17	2	2
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.01	0.011	-9999	-0.16	2	2
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.028	0.002	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.028	0	-9999	-10000	0	0
SUMO1/HDAC4	0.038	0.034	-9999	-0.26	2	2
SUMO1/HDAC1	0.038	0.031	-9999	-0.26	2	2
RANGAP1	0.026	0.02	-9999	-0.44	1	1
MDM2/SUMO1/SUMO1	0.052	0.037	-9999	-0.37	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.014	0.012	-9999	-0.17	2	2
Ran/GTP	0.025	0.027	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.027	0.016	-9999	-0.36	1	1
UBE2I	0.027	0.004	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.026	-9999	-10000	0	0
NPC	0.016	0	-9999	-10000	0	0
PIAS2	0.021	0.012	-9999	-10000	0	0
PIAS1	0.026	0.006	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.054	0.016	-9999	-0.21	1	1
E-cadherin/beta catenin	0.04	0.006	-9999	-10000	0	0
CTNNB1	0.027	0.003	-9999	-10000	0	0
JUP	0.027	0.016	-9999	-0.36	1	1
CDH1	0.028	0.003	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.039	0.01	-9999	-9999
FBXW11	0.027	0.004	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.004	-9999	-9999
CHUK	0.027	0.006	-9999	-9999
NF kappa B2 p100/RelB	0.076	0.023	-9999	-9999
NFKB1	0.027	0.005	-9999	-9999
MAP3K14	0.027	0.004	-9999	-9999
NF kappa B1 p50/RelB	0.04	0.008	-9999	-9999
RELB	0.027	0.003	-9999	-9999
NFKB2	0.027	0.006	-9999	-9999
NF kappa B2 p52/RelB	0.036	0.009	-9999	-9999
regulation of B cell activation	0.035	0.009	-9999	-9999

pid_entity	TCGA.WS.AB45	TCGA.T9.A92H	TCGA.SS.A7HO	TCGA.RU.A8FL
109_MAP3K5	0.031	0.031	-0.19	-0.17
47_PPARGC1A	0.028	0.028	0.028	0.028
105_BMP4	0.028	0	0	0.028
105_BMP6	0.028	0.028	0.028	0.028
105_BMP7	-0.36	0.028	0.028	0.36
105_BMP2	0.028	0.028	0	-0.36
131_RELN/VLDLR	-0.24	-0.41	-0.058	-0.23
30_TGFB1/TGF beta receptor Type II	0.027	0.027	0.03	0.032
84_STAT5B	0.0059	0.028	0	0.04
84_STAT5A	0.0059	0.028	0	0.04