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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	136
Reelin signaling pathway	119
Lissencephaly gene (LIS1) in neuronal migration and development	68
Ephrin A reverse signaling	65
IL4-mediated signaling events	58
BCR signaling pathway	57
Glypican 1 network	55
Signaling events mediated by Stem cell factor receptor (c-Kit)	52
Fc-epsilon receptor I signaling in mast cells	51
p75(NTR)-mediated signaling	49

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	0.2976	136	1095	8	-0.12	0.096	1000	-1000	-0.005	-1000
Reelin signaling pathway	0.2604	119	6673	56	-0.34	0.074	1000	-1000	-0.053	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1488	68	3703	54	-0.31	0.036	1000	-1000	-0.048	-1000
Ephrin A reverse signaling	0.1422	65	457	7	-0.051	0	1000	-1000	-0.017	-1000
IL4-mediated signaling events	0.1269	58	5286	91	-0.82	0.58	1000	-1000	-0.18	-1000
BCR signaling pathway	0.1247	57	5687	99	-0.21	0.029	1000	-1000	-0.057	-1000
Glypican 1 network	0.1204	55	2674	48	-0.16	0.052	1000	-1000	-0.034	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1138	52	4114	78	-0.19	0.081	1000	-1000	-0.055	-1000
Fc-epsilon receptor I signaling in mast cells	0.1116	51	4988	97	-0.16	0.05	1000	-1000	-0.069	-1000
p75(NTR)-mediated signaling	0.1072	49	6204	125	-0.44	0.07	1000	-1000	-0.075	-1000
FOXA2 and FOXA3 transcription factor networks	0.1050	48	2219	46	-0.61	0.031	1000	-1000	-0.13	-1000
HIF-1-alpha transcription factor network	0.1007	46	3540	76	-0.55	0.036	1000	-1000	-0.15	-1000
Signaling events regulated by Ret tyrosine kinase	0.0985	45	3722	82	-0.13	0.033	1000	-1000	-0.066	-1000
Visual signal transduction: Rods	0.0897	41	2163	52	-0.22	0.042	1000	-1000	-0.047	-1000
BMP receptor signaling	0.0788	36	2985	81	-0.2	0.051	1000	-1000	-0.058	-1000
Signaling events mediated by the Hedgehog family	0.0766	35	1853	52	-0.063	0.063	1000	-1000	-0.045	-1000
Syndecan-1-mediated signaling events	0.0744	34	1174	34	-0.41	0.029	1000	-1000	-0.052	-1000
Syndecan-2-mediated signaling events	0.0744	34	2370	69	-0.24	0.045	1000	-1000	-0.044	-1000
Endothelins	0.0744	34	3304	96	-0.25	0.056	1000	-1000	-0.074	-1000
Visual signal transduction: Cones	0.0722	33	1259	38	-0.11	0.037	1000	-1000	-0.018	-1000
LPA receptor mediated events	0.0722	33	3414	102	-0.16	0.035	1000	-1000	-0.06	-1000
JNK signaling in the CD4+ TCR pathway	0.0700	32	547	17	-0.13	0.032	1000	-1000	-0.046	-1000
amb2 Integrin signaling	0.0656	30	2525	82	-0.083	0.036	1000	-1000	-0.034	-1000
TCR signaling in naïve CD8+ T cells	0.0635	29	2733	93	-0.045	0.04	1000	-1000	-0.053	-1000
IGF1 pathway	0.0635	29	1675	57	-0.081	0.053	1000	-1000	-0.045	-1000
Effects of Botulinum toxin	0.0613	28	750	26	-0.069	0.046	1000	-1000	-0.013	-1000
IL23-mediated signaling events	0.0613	28	1731	60	-0.28	0.029	1000	-1000	-0.1	-1000
Osteopontin-mediated events	0.0591	27	1034	38	-0.19	0.039	1000	-1000	-0.053	-1000
Plasma membrane estrogen receptor signaling	0.0591	27	2354	86	-0.17	0.07	1000	-1000	-0.059	-1000
Ras signaling in the CD4+ TCR pathway	0.0591	27	472	17	-0.068	0.049	1000	-1000	-0.042	-1000
IL1-mediated signaling events	0.0569	26	1664	62	-0.14	0.062	1000	-1000	-0.045	-1000
S1P5 pathway	0.0569	26	444	17	-0.088	0.036	1000	-1000	-0.02	-1000
Ephrin B reverse signaling	0.0547	25	1208	48	-0.083	0.032	1000	-1000	-0.032	-1000
TCGA08_p53	0.0525	24	169	7	-0.059	0.027	1000	-1000	-0.006	-1000
Wnt signaling	0.0525	24	170	7	-0.065	0.023	1000	-1000	-0.018	-1000
Signaling events mediated by PRL	0.0525	24	832	34	-0.056	0.084	1000	-1000	-0.047	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0503	23	1206	52	-0.21	0.059	1000	-1000	-0.041	-1000
Canonical Wnt signaling pathway	0.0503	23	1193	51	-0.26	0.13	1000	-1000	-0.048	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0503	23	2027	88	-0.13	0.061	1000	-1000	-0.082	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0481	22	841	37	-0.18	0.058	1000	-1000	-0.044	-1000
Nongenotropic Androgen signaling	0.0481	22	1165	52	-0.088	0.063	1000	-1000	-0.047	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0481	22	2649	120	-0.11	0.094	1000	-1000	-0.056	-1000
LPA4-mediated signaling events	0.0460	21	261	12	-0.1	0.007	1000	-1000	-0.029	-1000
Presenilin action in Notch and Wnt signaling	0.0460	21	1292	61	-0.26	0.13	1000	-1000	-0.054	-1000
IL12-mediated signaling events	0.0438	20	1825	87	-0.13	0.048	1000	-1000	-0.091	-1000
Syndecan-3-mediated signaling events	0.0438	20	700	35	-0.24	0.07	1000	-1000	-0.034	-1000
Signaling mediated by p38-alpha and p38-beta	0.0438	20	885	44	-0.036	0.028	1000	-1000	-0.037	-1000
S1P4 pathway	0.0438	20	511	25	-0.088	0.041	1000	-1000	-0.031	-1000
Calcium signaling in the CD4+ TCR pathway	0.0416	19	610	31	-0.27	0.027	1000	-1000	-0.06	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0416	19	1309	68	-0.29	0.044	1000	-1000	-0.11	-1000
EGFR-dependent Endothelin signaling events	0.0416	19	401	21	-0.062	0.04	1000	-1000	-0.048	-1000
Thromboxane A2 receptor signaling	0.0394	18	1982	105	-0.18	0.069	1000	-1000	-0.055	-1000
Arf6 signaling events	0.0394	18	1150	62	-0.12	0.061	1000	-1000	-0.048	-1000
Glucocorticoid receptor regulatory network	0.0394	18	2103	114	-0.31	0.19	1000	-1000	-0.06	-1000
Syndecan-4-mediated signaling events	0.0394	18	1247	67	-0.25	0.038	1000	-1000	-0.048	-1000
a4b1 and a4b7 Integrin signaling	0.0372	17	86	5	0.01	0.028	1000	-1000	0.001	-1000
Nectin adhesion pathway	0.0350	16	1059	63	-0.39	0.076	1000	-1000	-0.043	-1000
Integrins in angiogenesis	0.0350	16	1411	84	-0.19	0.065	1000	-1000	-0.049	-1000
EPHB forward signaling	0.0350	16	1395	85	-0.085	0.09	1000	-1000	-0.076	-1000
Regulation of Androgen receptor activity	0.0350	16	1132	70	-0.22	0.058	1000	-1000	-0.059	-1000
Caspase cascade in apoptosis	0.0328	15	1177	74	-0.089	0.063	1000	-1000	-0.036	-1000
PDGFR-beta signaling pathway	0.0328	15	1525	97	-0.15	0.092	1000	-1000	-0.071	-1000
Noncanonical Wnt signaling pathway	0.0306	14	377	26	-0.065	0.027	1000	-1000	-0.044	-1000
Ceramide signaling pathway	0.0306	14	1123	76	-0.079	0.069	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class III	0.0306	14	561	40	-0.15	0.052	1000	-1000	-0.02	-1000
FAS signaling pathway (CD95)	0.0306	14	690	47	-0.037	0.044	1000	-1000	-0.029	-1000
Regulation of p38-alpha and p38-beta	0.0306	14	780	54	-0.1	0.052	1000	-1000	-0.05	-1000
Glypican 2 network	0.0306	14	57	4	0.013	0.025	1000	-1000	0.004	-1000
Signaling events mediated by PTP1B	0.0284	13	1054	76	-0.2	0.047	1000	-1000	-0.05	-1000
IL6-mediated signaling events	0.0284	13	1014	75	-0.072	0.07	1000	-1000	-0.068	-1000
S1P3 pathway	0.0284	13	570	42	-0.087	0.045	1000	-1000	-0.038	-1000
Regulation of nuclear SMAD2/3 signaling	0.0263	12	1710	136	-0.5	0.072	1000	-1000	-0.055	-1000
HIF-2-alpha transcription factor network	0.0263	12	540	43	-0.36	0.18	1000	-1000	-0.089	-1000
S1P1 pathway	0.0263	12	433	36	-0.087	0.042	1000	-1000	-0.056	-1000
Aurora B signaling	0.0263	12	826	67	-0.39	0.091	1000	-1000	-0.046	-1000
ErbB2/ErbB3 signaling events	0.0241	11	720	65	-0.048	0.04	1000	-1000	-0.064	-1000
Cellular roles of Anthrax toxin	0.0241	11	433	39	-0.04	0.032	1000	-1000	-0.023	-1000
PLK1 signaling events	0.0241	11	944	85	-0.01	0.06	1000	-1000	-0.039	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0241	11	389	33	-0.071	0.065	1000	-1000	-0.035	-1000
ErbB4 signaling events	0.0219	10	726	69	-0.16	0.076	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0219	10	288	28	-0.088	0.042	1000	-1000	-0.026	-1000
FoxO family signaling	0.0219	10	648	64	-0.12	0.051	1000	-1000	-0.073	-1000
Class I PI3K signaling events	0.0219	10	781	73	-0.1	0.044	1000	-1000	-0.049	-1000
VEGFR1 specific signals	0.0219	10	579	56	-0.015	0.091	1000	-1000	-0.055	-1000
Coregulation of Androgen receptor activity	0.0197	9	753	76	-0.19	0.061	1000	-1000	-0.025	-1000
Class I PI3K signaling events mediated by Akt	0.0197	9	650	68	-0.051	0.06	1000	-1000	-0.036	-1000
Signaling mediated by p38-gamma and p38-delta	0.0197	9	145	15	-0.055	0.027	1000	-1000	-0.035	-1000
Retinoic acid receptors-mediated signaling	0.0197	9	524	58	-0.14	0.05	1000	-1000	-0.045	-1000
Insulin-mediated glucose transport	0.0175	8	264	32	-0.14	0.044	1000	-1000	-0.031	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0175	8	742	83	-0.12	0.07	1000	-1000	-0.047	-1000
Arf6 trafficking events	0.0175	8	601	71	-0.046	0.048	1000	-1000	-0.033	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0153	7	263	34	-0.028	0.065	1000	-1000	-0.04	-1000
Arf6 downstream pathway	0.0153	7	324	43	-0.028	0.042	1000	-1000	-0.033	-1000
EPO signaling pathway	0.0153	7	402	55	-0.015	0.065	1000	-1000	-0.051	-1000
PDGFR-alpha signaling pathway	0.0153	7	311	44	-0.013	0.062	1000	-1000	-0.048	-1000
ceramide signaling pathway	0.0153	7	367	49	0	0.044	1000	-1000	-0.036	-1000
IL27-mediated signaling events	0.0153	7	402	51	-0.067	0.038	1000	-1000	-0.057	-1000
Hedgehog signaling events mediated by Gli proteins	0.0131	6	390	65	-0.087	0.05	1000	-1000	-0.054	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0131	6	304	45	-0.017	0.073	1000	-1000	-0.055	-1000
TCGA08_rtk_signaling	0.0131	6	166	26	-0.035	0.061	1000	-1000	-0.021	-1000
Regulation of Telomerase	0.0131	6	700	102	-0.19	0.063	1000	-1000	-0.059	-1000
Rapid glucocorticoid signaling	0.0131	6	122	20	-0.017	0.026	1000	-1000	-0.008	-1000
FOXM1 transcription factor network	0.0131	6	355	51	-0.097	0.11	1000	-1000	-0.14	-1000
Signaling events mediated by HDAC Class II	0.0109	5	391	75	-0.031	0.069	1000	-1000	-0.039	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0109	5	506	85	-0.039	0.065	1000	-1000	-0.051	-1000
mTOR signaling pathway	0.0109	5	310	53	-0.076	0.038	1000	-1000	-0.038	-1000
IFN-gamma pathway	0.0109	5	354	68	-0.035	0.042	1000	-1000	-0.066	-1000
IL2 signaling events mediated by PI3K	0.0109	5	318	58	-0.014	0.047	1000	-1000	-0.048	-1000
E-cadherin signaling in the nascent adherens junction	0.0109	5	385	76	-0.012	0.089	1000	-1000	-0.059	-1000
Aurora A signaling	0.0088	4	266	60	-0.083	0.075	1000	-1000	-0.025	-1000
Paxillin-dependent events mediated by a4b1	0.0088	4	178	36	-0.047	0.049	1000	-1000	-0.04	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0088	4	300	74	-0.079	0.064	1000	-1000	-0.068	-1000
Class IB PI3K non-lipid kinase events	0.0088	4	12	3	-0.023	0.023	1000	-1000	-0.003	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0066	3	423	125	-0.01	0.096	1000	-1000	-0.061	-1000
Insulin Pathway	0.0066	3	231	74	-0.029	0.084	1000	-1000	-0.052	-1000
p38 MAPK signaling pathway	0.0066	3	137	44	-0.012	0.059	1000	-1000	-0.034	-1000
Arf1 pathway	0.0066	3	202	54	0	0.042	1000	-1000	-0.022	-1000
PLK2 and PLK4 events	0.0044	2	8	3	0.01	0.026	1000	-1000	-0.017	-1000
TRAIL signaling pathway	0.0044	2	137	48	-0.007	0.059	1000	-1000	-0.039	-1000
IL2 signaling events mediated by STAT5	0.0044	2	59	22	0.005	0.042	1000	-1000	-0.054	-1000
Canonical NF-kappaB pathway	0.0022	1	75	39	0	0.06	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class I	0.0022	1	184	104	-0.053	0.065	1000	-1000	-0.039	-1000
Atypical NF-kappaB pathway	0.0022	1	36	31	0	0.056	1000	-1000	-0.029	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	9	23	0.012	0.041	1000	-1000	-0.03	-1000
BARD1 signaling events	0.0000	0	25	57	-0.055	0.078	1000	-1000	-0.05	-1000
Circadian rhythm pathway	0.0000	0	18	22	-0.009	0.064	1000	-1000	-0.045	-1000
Aurora C signaling	0.0000	0	5	7	0	0.041	1000	-1000	-0.015	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	16	27	0	0.052	1000	-1000	-0.041	-1000
E-cadherin signaling in keratinocytes	0.0000	0	26	43	-0.047	0.087	1000	-1000	-0.04	-1000
E-cadherin signaling events	0.0000	0	2	5	0.026	0.053	1000	-1000	-0.002	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.075	1000	-1000	-0.006	-1000
Total	NA	2502	145975	7203	-16	7.9	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	-0.12	0.19	-10000	0	-0.36	171	171
CDKN2C	0.034	0.026	-10000	0	-10000	0	0
CDKN2A	-0.075	0.2	0.35	2	-0.44	97	99
CCND2	0.086	0.1	0.2	179	-0.35	1	180
RB1	-0.071	0.1	0.27	6	-0.21	142	148
CDK4	0.087	0.1	0.21	167	-0.25	2	169
CDK6	0.096	0.11	0.22	177	-0.38	1	178
G1/S progression	0.075	0.11	0.2	144	-0.27	6	150

×

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	0.019	-10000	0	-0.3	1	1
VLDLR	-0.008	0.12	-10000	0	-0.4	37	37
CRKL	0.026	0.006	-10000	0	-10000	0	0
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
ITGA3	0.026	0.02	-10000	0	-0.4	1	1
RELN/VLDLR/Fyn	-0.085	0.16	-10000	0	-0.26	190	190
MAPK8IP1/MKK7/MAP3K11/JNK1	0.074	0.037	-10000	0	-0.56	1	1
AKT1	-0.094	0.13	-10000	0	-0.35	52	52
MAP2K7	0.026	0.02	-10000	0	-0.4	1	1
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1
DAB1	-0.026	0.14	-10000	0	-0.44	43	43
RELN/LRP8/DAB1	-0.26	0.17	-10000	0	-0.32	375	375
LRPAP1/LRP8	-0.21	0.15	0.26	1	-0.3	327	328
RELN/LRP8/DAB1/Fyn	-0.25	0.16	-10000	0	-0.31	369	369
DAB1/alpha3/beta1 Integrin	-0.24	0.17	-10000	0	-0.42	170	170
long-term memory	-0.34	0.2	-10000	0	-0.47	266	266
DAB1/LIS1	-0.25	0.17	-10000	0	-0.42	176	176
DAB1/CRLK/C3G	-0.24	0.17	-10000	0	-0.42	174	174
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
DAB1/NCK2	-0.25	0.18	-10000	0	-0.43	176	176
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	-0.093	0.18	-10000	0	-0.4	114	114
CDK5R1	0.026	0.022	-10000	0	-0.43	1	1
RELN	-0.15	0.21	-10000	0	-0.4	187	187
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.26	0.17	0.25	1	-0.34	363	364
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.29	0.19	-10000	0	-0.37	344	344
MAPK8	0.027	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.1	0.16	-10000	0	-0.25	216	216
ITGB1	0.027	0.002	-10000	0	-10000	0	0
MAP1B	-0.26	0.18	-10000	0	-0.42	194	194
RELN/LRP8	-0.26	0.17	0.25	1	-0.33	363	364
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.3	0.19	-10000	0	-0.37	352	352
PI3K	0.039	0.008	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.039	0.016	-10000	0	-0.28	1	1
RAP1A	-0.24	0.15	0.3	1	-0.4	172	173
PAFAH1B1	0.023	0.01	-10000	0	-10000	0	0
MAPK8IP1	0.026	0.02	-10000	0	-0.4	1	1
CRLK/C3G	0.038	0.018	-10000	0	-0.28	1	1
GRIN2B	-0.09	0.2	-10000	0	-0.43	115	115
NCK2	0.027	0	-10000	0	-10000	0	0
neuron differentiation	-0.12	0.12	0.23	1	-0.26	154	155
neuron adhesion	-0.23	0.15	0.29	1	-0.39	164	165
LRP8	-0.31	0.2	0.36	1	-0.43	329	330
GSK3B	-0.091	0.13	-10000	0	-0.34	51	51
RELN/VLDLR/DAB1/Fyn	-0.088	0.16	-10000	0	-0.24	208	208
MAP3K11	0.026	0.02	-10000	0	-0.4	1	1
RELN/VLDLR/DAB1/P13K	-0.1	0.14	-10000	0	-0.25	194	194
CDK5	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.055	0.18	0.85	6	-0.35	92	98
neuron migration	-0.22	0.17	0.23	3	-0.41	166	169
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.12	-10000	0	-0.26	154	154
RELN/VLDLR	-0.25	0.18	0.26	1	-0.32	359	360

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.025	0.007	-10000	0	-10000	0	0
VLDLR	-0.008	0.12	-10000	0	-0.4	37	37
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
NUDC	0.025	0.007	-10000	0	-10000	0	0
RELN/LRP8	-0.26	0.17	0.25	1	-0.33	363	364
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	8	-0.31	350	358
IQGAP1/CaM	0.036	0.013	-10000	0	-10000	0	0
DAB1	-0.026	0.14	-10000	0	-0.44	43	43
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
PLA2G7	0.023	0.044	-10000	0	-0.4	5	5
CALM1	0.025	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	0.15	0.26	1	-0.3	327	328
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.026	0.02	-10000	0	-0.4	1	1
CDK5R1	0.026	0.022	-10000	0	-0.43	1	1
LIS1/Poliovirus Protein 3A	0.007	0.005	-10000	0	-10000	0	0
CDK5R2	-0.023	0.13	-10000	0	-0.4	45	45
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.17	-10000	0	-0.28	216	216
YWHAE	0.023	0.01	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.21	0.15	0.32	3	-0.36	162	165
MAP1B	0	0.037	-10000	0	-0.27	8	8
RAC1	0.01	0.007	-10000	0	-10000	0	0
p35/CDK5	-0.22	0.14	0.18	3	-0.38	141	144
RELN	-0.15	0.21	-10000	0	-0.4	187	187
PAFAH/LIS1	0.02	0.027	-10000	0	-0.22	4	4
LIS1/CLIP170	0.021	0.018	-10000	0	-0.24	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.17	0.12	-10000	0	-0.31	143	143
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.09	0.16	-10000	0	-0.35	72	72
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.22	0.15	0.32	3	-0.38	171	174
LIS1/IQGAP1	0.022	0.014	-10000	0	-10000	0	0
RHOA	0.011	0.007	-10000	0	-10000	0	0
PAFAH1B1	0.01	0.006	-10000	0	-10000	0	0
PAFAH1B3	0.02	0.056	-10000	0	-0.43	7	7
PAFAH1B2	0.027	0.004	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.013	0.038	-10000	0	-0.24	2	2
NDEL1/Katanin 60/Dynein heavy chain	-0.2	0.15	0.32	3	-0.36	162	165
LRP8	-0.31	0.2	0.36	1	-0.43	329	330
NDEL1/Katanin 60	-0.21	0.15	0.32	3	-0.36	165	168
P39/CDK5	-0.24	0.15	0.18	2	-0.4	167	169
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0.014	-10000	0	-10000	0	0
CDK5	-0.23	0.14	0.18	4	-0.4	144	148
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0.016	-10000	0	-0.2	1	1
CSNK2A1	0.022	0.011	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.085	0.15	-10000	0	-0.34	56	56
RELN/VLDLR	-0.25	0.18	0.26	1	-0.32	359	360
CDC42	0.01	0.019	-10000	0	-0.37	1	1

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.025	0.11	-10000	0	-0.24	92	92
EFNA5	-0.051	0.16	-10000	0	-0.4	82	82
FYN	-0.042	0.093	0.18	1	-0.22	84	85
neuron projection morphogenesis	-0.025	0.11	-10000	0	-0.24	92	92
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.025	0.11	-10000	0	-0.24	92	92
EPHA5	-0.007	0.073	-10000	0	-0.4	14	14

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.46	0.49	-10000	0	-1.2	86	86
STAT6 (cleaved dimer)	-0.57	0.52	-10000	0	-1.2	141	141
IGHG1	-0.17	0.16	-10000	0	-0.39	4	4
IGHG3	-0.5	0.46	-10000	0	-1.1	117	117
AKT1	-0.28	0.29	-10000	0	-0.81	49	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.24	-10000	0	-0.85	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.28	0.29	-10000	0	-1.1	22	22
THY1	-0.53	0.48	-10000	0	-1.2	104	104
MYB	0.026	0.02	-10000	0	-0.4	1	1
HMGA1	0.028	0.016	0.36	1	-10000	0	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.36	-10000	0	-0.84	126	126
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.28	0.29	-10000	0	-1.1	23	23
SP1	0.027	0.02	-10000	0	-10000	0	0
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
SOCS5	0.046	0.026	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.51	-10000	0	-1.2	130	130
SOCS1	-0.38	0.31	-10000	0	-0.77	100	100
SOCS3	-0.33	0.3	-10000	0	-0.78	69	69
FCER2	-0.82	0.65	-10000	0	-1.4	241	241
PARP14	0.009	0.03	-10000	0	-10000	0	0
CCL17	-0.52	0.48	-10000	0	-1.2	95	95
GRB2	0.027	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.21	-10000	0	-0.71	21	21
T cell proliferation	-0.53	0.5	-10000	0	-1.2	105	105
IL4R/JAK1	-0.53	0.49	-10000	0	-1.2	106	106
EGR2	-0.6	0.52	-10000	0	-1.3	113	113
JAK2	-0.034	0.052	-10000	0	-0.43	3	3
JAK3	0.011	0.034	-10000	0	-0.43	1	1
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	-0.007	0.025	-10000	0	-10000	0	0
COL1A2	-0.15	0.16	-10000	0	-0.69	1	1
CCL26	-0.54	0.49	-10000	0	-1.2	99	99
IL4R	-0.56	0.51	-10000	0	-1.3	100	100
PTPN6	0.038	0.014	-10000	0	-10000	0	0
IL13RA2	-0.54	0.48	-10000	0	-1.2	98	98
IL13RA1	-0.032	0.041	-10000	0	-10000	0	0
IRF4	-0.53	0.67	-10000	0	-1.4	150	150
ARG1	-0.092	0.14	-10000	0	-0.6	7	7
CBL	-0.37	0.34	-10000	0	-0.81	119	119
GTF3A	0.022	0.07	0.34	15	-0.42	1	16
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.038	0.062	-10000	0	-0.31	3	3
IRF4/BCL6	-0.46	0.62	-10000	0	-1.3	150	150
CD40LG	-0.05	0.12	-10000	0	-0.41	35	35
MAPK14	-0.36	0.34	-10000	0	-0.82	114	114
mitosis	-0.27	0.27	-10000	0	-0.76	47	47
STAT6	-0.59	0.57	-10000	0	-1.4	114	114
SPI1	0.023	0.049	-10000	0	-0.39	6	6
RPS6KB1	-0.26	0.26	-10000	0	-0.75	39	39
STAT6 (dimer)	-0.59	0.57	-10000	0	-1.4	114	114
STAT6 (dimer)/PARP14	-0.6	0.54	-10000	0	-1.3	123	123
mast cell activation	0.014	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.29	-10000	0	-0.77	69	69
FRAP1	-0.28	0.29	-10000	0	-0.81	48	48
LTA	-0.52	0.49	-10000	0	-1.3	94	94
FES	0.025	0.021	-10000	0	-0.4	1	1
T-helper 1 cell differentiation	0.58	0.55	1.3	116	-10000	0	116
CCL11	-0.56	0.55	-10000	0	-1.4	111	111
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.28	0.27	-10000	0	-0.76	46	46
IL2RG	0.011	0.038	-10000	0	-0.39	2	2
IL10	-0.55	0.52	-10000	0	-1.3	113	113
IRS1	0.027	0.002	-10000	0	-10000	0	0
IRS2	0.021	0.012	-10000	0	-10000	0	0
IL4	-0.14	0.19	-10000	0	-1.1	11	11
IL5	-0.52	0.48	-10000	0	-1.2	95	95
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.42	0.38	-10000	0	-0.96	82	82
COL1A1	-0.19	0.2	-10000	0	-0.75	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.54	0.5	-10000	0	-1.3	94	94
IL2R gamma/JAK3	0.013	0.047	-10000	0	-0.29	3	3
TFF3	-0.54	0.51	-10000	0	-1.3	101	101
ALOX15	-0.55	0.5	-10000	0	-1.2	112	112
MYBL1	0.022	0.031	-10000	0	-0.43	2	2
T-helper 2 cell differentiation	-0.44	0.4	-10000	0	-0.98	103	103
SHC1	0.027	0.004	-10000	0	-10000	0	0
CEBPB	0.017	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.25	0.28	-10000	0	-1	23	23
mol:PI-3-4-5-P3	-0.28	0.29	-10000	0	-0.81	47	47
PI3K	-0.3	0.31	-10000	0	-0.89	46	46
DOK2	0.015	0.049	-10000	0	-0.4	6	6
ETS1	0.036	0.028	-10000	0	-0.36	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.2	-10000	0	-0.63	25	25
ITGB3	-0.52	0.49	-10000	0	-1.2	104	104
PIGR	-0.7	0.65	-10000	0	-1.5	166	166
IGHE	0.083	0.074	0.18	115	-10000	0	115
MAPKKK cascade	-0.2	0.19	-10000	0	-0.62	25	25
BCL6	0.033	0.01	-10000	0	-10000	0	0
OPRM1	-0.53	0.48	-10000	0	-1.2	95	95
RETNLB	-0.75	0.66	-10000	0	-1.4	192	192
SELP	-0.59	0.58	-10000	0	-1.4	113	113
AICDA	-0.51	0.46	-10000	0	-1.2	104	104

×

BCR signaling pathway

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
JUN	-0.13	0.21	0.2	1	-0.48	95	96
IKBKB	-0.04	0.11	0.21	3	-0.29	35	38
AKT1	-0.085	0.11	0.17	3	-0.26	96	99
IKBKG	-0.042	0.11	0.22	1	-0.29	40	41
CALM1	-0.11	0.23	0.3	1	-0.55	81	82
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
MAP3K1	-0.16	0.28	0.25	1	-0.65	93	94
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.12	0.25	0.32	1	-0.57	85	86
DOK1	0.027	0.002	-10000	0	-10000	0	0
AP-1	-0.074	0.12	0.21	1	-0.28	82	83
LYN	0.024	0.01	-10000	0	-10000	0	0
BLNK	0.022	0.045	-10000	0	-0.4	5	5
SHC1	0.027	0.004	-10000	0	-10000	0	0
BCR complex	-0.11	0.2	-10000	0	-0.36	163	163
CD22	-0.2	0.32	-10000	0	-0.68	115	115
CAMK2G	-0.1	0.21	0.27	2	-0.51	79	81
CSNK2A1	0.022	0.011	-10000	0	-10000	0	0
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
SHC/GRB2/SOS1	-0.059	0.14	-10000	0	-0.36	48	48
GO:0007205	-0.12	0.26	0.32	1	-0.58	85	86
SYK	0.027	0.004	-10000	0	-10000	0	0
ELK1	-0.12	0.24	0.3	1	-0.56	81	82
NFATC1	-0.17	0.26	-10000	0	-0.55	117	117
B-cell antigen/BCR complex	-0.11	0.2	-10000	0	-0.36	163	163
PAG1/CSK	0.029	0.039	-10000	0	-0.27	6	6
NFKBIB	-0.001	0.048	0.11	4	-0.13	22	26
HRAS	-0.095	0.2	0.31	1	-0.48	77	78
NFKBIA	0	0.046	0.11	4	-0.12	21	25
NF-kappa-B/RelA/I kappa B beta	0.005	0.04	0.11	4	-10000	0	4
RasGAP/Csk	-0.069	0.2	-10000	0	-0.45	71	71
mol:GDP	-0.11	0.24	0.31	1	-0.56	82	83
PTEN	0.026	0.006	-10000	0	-10000	0	0
CD79B	-0.034	0.15	-10000	0	-0.4	64	64
NF-kappa-B/RelA/I kappa B alpha	0.006	0.039	0.11	4	-10000	0	4
GRB2	0.027	0.004	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.18	0.27	-10000	0	-0.56	131	131
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.12	0.26	0.32	1	-0.59	85	86
CSK	0.026	0.006	-10000	0	-10000	0	0
FOS	-0.11	0.22	0.29	1	-0.52	81	82
CHUK	-0.05	0.12	0.22	1	-0.3	54	55
IBTK	0.026	0.02	-10000	0	-0.4	1	1
CARD11/BCL10/MALT1/TAK1	-0.081	0.22	0.27	1	-0.51	70	71
PTPN6	-0.19	0.3	-10000	0	-0.64	115	115
RELA	0.027	0.004	-10000	0	-10000	0	0
BCL2A1	0.005	0.029	-10000	0	-0.13	1	1
VAV2	-0.2	0.32	-10000	0	-0.67	122	122
ubiquitin-dependent protein catabolic process	0.001	0.047	0.12	4	-0.12	21	25
BTK	-0.12	0.37	-10000	0	-1.1	60	60
CD19	-0.2	0.32	-10000	0	-0.65	124	124
MAP4K1	-0.016	0.13	-10000	0	-0.4	46	46
CD72	0.026	0.021	-10000	0	-0.4	1	1
PAG1	0.018	0.049	-10000	0	-0.4	6	6
MAPK14	-0.13	0.24	0.24	1	-0.54	91	92
SH3BP5	0.024	0.035	-10000	0	-0.4	3	3
PIK3AP1	-0.11	0.25	0.34	2	-0.59	80	82
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.16	0.31	-10000	0	-0.67	89	89
RAF1	-0.091	0.19	0.3	1	-0.46	73	74
RasGAP/p62DOK/SHIP	-0.064	0.2	-10000	0	-0.44	71	71
CD79A	-0.13	0.2	-10000	0	-0.4	164	164
re-entry into mitotic cell cycle	-0.074	0.12	0.21	1	-0.28	82	83
RASA1	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.077	0.16	0.27	1	-0.4	66	67
MAPK1	-0.076	0.16	0.27	1	-0.41	61	62
CD72/SHP1	-0.16	0.29	-10000	0	-0.61	111	111
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.13	0.24	0.24	1	-0.54	90	91
actin cytoskeleton organization	-0.16	0.26	0.33	1	-0.55	117	118
NF-kappa-B/RelA	0.015	0.079	0.22	4	-0.2	14	18
Calcineurin	-0.078	0.2	0.28	1	-0.49	67	68
PI3K	-0.17	0.24	-10000	0	-0.49	132	132
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.12	0.27	0.36	1	-0.6	87	88
SOS1	0.027	0.002	-10000	0	-10000	0	0
Bam32/HPK1	-0.19	0.37	-10000	0	-0.88	88	88
DAPP1	-0.21	0.41	-10000	0	-0.97	88	88
cytokine secretion	-0.16	0.24	-10000	0	-0.5	117	117
mol:DAG	-0.12	0.26	0.32	1	-0.59	85	86
PLCG2	-0.015	0.13	-10000	0	-0.4	45	45
MAP2K1	-0.084	0.17	0.29	1	-0.44	66	67
B-cell antigen/BCR complex/FcgammaRIIB	-0.099	0.22	-10000	0	-0.36	164	164
mol:PI-3-4-5-P3	-0.12	0.15	0.17	1	-0.34	124	125
ETS1	-0.097	0.19	0.26	2	-0.48	74	76
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.047	0.16	-10000	0	-0.39	50	50
B-cell antigen/BCR complex/LYN	-0.15	0.3	-10000	0	-0.69	87	87
MALT1	0.02	0.023	-10000	0	-0.4	1	1
TRAF6	0.027	0.004	-10000	0	-10000	0	0
RAC1	-0.17	0.29	-10000	0	-0.6	117	117
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.3	-10000	0	-0.64	105	105
CARD11	-0.11	0.26	0.27	8	-0.58	80	88
FCGR2B	-0.021	0.13	-10000	0	-0.4	51	51
PPP3CA	0.027	0.005	-10000	0	-10000	0	0
BCL10	0.026	0.021	-10000	0	-0.4	1	1
IKK complex	-0.013	0.049	0.14	7	-0.12	11	18
PTPRC	-0.007	0.12	-10000	0	-0.4	36	36
PDPK1	-0.085	0.1	0.15	4	-0.25	93	97
PPP3CB	0.027	0.004	-10000	0	-10000	0	0
PPP3CC	0.021	0.012	-10000	0	-10000	0	0
POU2F2	0.003	0.032	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.028	0.072	-10000	0	-0.23	29	29
fibroblast growth factor receptor signaling pathway	0.028	0.071	-10000	0	-0.23	29	29
LAMA1	-0.057	0.16	-10000	0	-0.4	84	84
PRNP	0.021	0.022	-10000	0	-0.4	1	1
GPC1/SLIT2	-0.044	0.14	-10000	0	-0.28	117	117
SMAD2	0.012	0.025	0.18	3	-0.23	1	4
GPC1/PrPc/Cu2+	0.028	0.027	-10000	0	-0.24	3	3
GPC1/Laminin alpha1	-0.028	0.12	-10000	0	-0.28	86	86
TDGF1	-0.16	0.22	-10000	0	-0.42	185	185
CRIPTO/GPC1	-0.1	0.17	-10000	0	-0.3	186	186
APP/GPC1	0.037	0.024	-10000	0	-0.29	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.094	0.13	-10000	0	-0.25	186	186
FLT1	0.021	0.012	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.052	0.026	-10000	0	-0.24	3	3
SERPINC1	0.006	0.051	-10000	0	-0.43	5	5
FYN	-0.096	0.13	-10000	0	-0.26	184	184
FGR	-0.097	0.14	-10000	0	-0.26	186	186
positive regulation of MAPKKK cascade	-0.04	0.13	0.22	29	-0.32	34	63
SLIT2	-0.083	0.18	-10000	0	-0.4	115	115
GPC1/NRG	-0.002	0.096	-10000	0	-0.28	47	47
NRG1	-0.022	0.12	-10000	0	-0.4	45	45
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.041	0.033	0.25	1	-0.25	2	3
LYN	-0.088	0.13	-10000	0	-0.26	165	165
mol:Spermine	0.006	0.02	-10000	0	-0.29	2	2
cell growth	0.028	0.071	-10000	0	-0.23	29	29
BMP signaling pathway	-0.025	0.029	0.41	2	-10000	0	2
SRC	-0.051	0.1	-10000	0	-0.26	84	84
TGFBR1	0.026	0.02	-10000	0	-0.4	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.068	0.18	-10000	0	-0.4	98	98
GPC1	0.025	0.029	-10000	0	-0.41	2	2
TGFBR1 (dimer)	0.026	0.02	-10000	0	-0.4	1	1
VEGFA	0.028	0.016	0.36	1	-10000	0	1
BLK	-0.16	0.16	-10000	0	-0.29	259	259
HCK	-0.054	0.11	-10000	0	-0.26	87	87
FGF2	-0.002	0.1	-10000	0	-0.4	30	30
FGFR1	0.021	0.035	-10000	0	-0.4	3	3
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	-0.29	2	2
ATIII/GPC1	0.032	0.042	-10000	0	-0.3	7	7
PLA2G2A/GPC1	-0.034	0.13	-10000	0	-0.28	100	100
LCK	-0.1	0.14	-10000	0	-0.26	190	190
neuron differentiation	-0.002	0.096	-10000	0	-0.28	47	47
PrPc/Cu2+	0.016	0.016	-10000	0	-0.28	1	1
APP	0.026	0.006	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.027	0.003	-10000	0	-10000	0	0

×

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	-0.074	0.18	-10000	0	-0.42	80	80
CRKL	-0.061	0.17	-10000	0	-0.41	79	79
HRAS	-0.047	0.16	-10000	0	-0.37	80	80
mol:PIP3	-0.048	0.16	0.26	2	-0.38	75	77
SPRED1	0.025	0.007	-10000	0	-10000	0	0
SPRED2	0.027	0.002	-10000	0	-10000	0	0
GAB1	-0.062	0.18	-10000	0	-0.43	79	79
FOXO3	-0.057	0.19	0.27	1	-0.41	84	85
AKT1	-0.061	0.2	0.28	1	-0.44	84	85
BAD	-0.057	0.19	0.27	1	-0.41	84	85
megakaryocyte differentiation	-0.081	0.19	-10000	0	-0.44	83	83
GSK3B	-0.057	0.19	0.27	1	-0.41	83	84
RAF1	-0.038	0.14	0.24	1	-0.31	77	78
SHC1	0.027	0.004	-10000	0	-10000	0	0
STAT3	-0.063	0.18	-10000	0	-0.43	78	78
STAT1	-0.16	0.41	-10000	0	-0.97	86	86
HRAS/SPRED1	-0.027	0.14	-10000	0	-0.31	70	70
cell proliferation	-0.062	0.17	-10000	0	-0.42	79	79
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
TEC	0.026	0.022	-10000	0	-0.43	1	1
RPS6KB1	-0.057	0.19	-10000	0	-0.43	83	83
HRAS/SPRED2	-0.027	0.14	-10000	0	-0.31	77	77
LYN/TEC/p62DOK	-0.026	0.18	-10000	0	-0.41	66	66
MAPK3	-0.026	0.1	0.21	2	-0.26	28	30
STAP1	-0.1	0.2	-10000	0	-0.48	84	84
GRAP2	0.012	0.073	-10000	0	-0.4	14	14
JAK2	-0.13	0.35	-10000	0	-0.83	82	82
STAT1 (dimer)	-0.15	0.4	-10000	0	-0.94	86	86
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.038	0.2	-10000	0	-0.44	77	77
actin filament polymerization	-0.061	0.17	0.21	1	-0.42	76	77
LYN	0.024	0.009	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.12	0.26	-10000	0	-0.64	81	81
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.033	0.17	-10000	0	-0.38	76	76
PI3K	-0.032	0.19	-10000	0	-0.42	80	80
PTEN	0.026	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.16	0.48	-10000	0	-1.2	78	78
MAPK8	-0.063	0.18	-10000	0	-0.43	79	79
STAT3 (dimer)	-0.062	0.17	-10000	0	-0.42	78	78
positive regulation of transcription	-0.019	0.086	0.2	2	-0.22	25	27
mol:GDP	-0.045	0.18	-10000	0	-0.39	79	79
PIK3C2B	-0.063	0.18	-10000	0	-0.43	77	77
CBL/CRKL	-0.044	0.17	-10000	0	-0.39	77	77
FER	-0.064	0.18	-10000	0	-0.43	79	79
SH2B3	-0.063	0.18	-10000	0	-0.43	79	79
PDPK1	-0.045	0.15	0.26	2	-0.36	74	76
SNAI2	-0.062	0.17	-10000	0	-0.42	73	73
positive regulation of cell proliferation	-0.11	0.3	-10000	0	-0.72	82	82
KITLG	0.009	0.07	-10000	0	-0.42	10	10
cell motility	-0.11	0.3	-10000	0	-0.72	82	82
PTPN6	0.03	0.01	-10000	0	-10000	0	0
EPOR	-0.019	0.15	-10000	0	-1	2	2
STAT5A (dimer)	-0.083	0.25	-10000	0	-0.59	80	80
SOCS1	0.017	0.067	-10000	0	-0.43	10	10
cell migration	0.081	0.19	0.46	79	-10000	0	79
SOS1	0.027	0.002	-10000	0	-10000	0	0
EPO	0.012	0.045	0.36	1	-0.43	3	4
VAV1	0.007	0.089	-10000	0	-0.4	21	21
GRB10	-0.062	0.17	-10000	0	-0.42	73	73
PTPN11	0.029	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.063	0.18	-10000	0	-0.45	80	80
GO:0007205	0.003	0.009	-10000	0	-10000	0	0
MAP2K1	-0.031	0.11	0.22	2	-0.28	27	29
CBL	0.027	0.004	-10000	0	-10000	0	0
KIT	-0.19	0.49	-10000	0	-1.2	78	78
MAP2K2	-0.031	0.11	0.22	2	-0.29	28	30
SHC/Grb2/SOS1	-0.025	0.18	-10000	0	-0.42	74	74
STAT5A	-0.087	0.25	-10000	0	-0.61	80	80
GRB2	0.027	0.004	-10000	0	-10000	0	0
response to radiation	-0.061	0.17	-10000	0	-0.42	73	73
SHC/GRAP2	0.028	0.056	-10000	0	-0.28	14	14
PTPRO	-0.083	0.19	-10000	0	-0.45	83	83
SH2B2	-0.063	0.17	0.21	1	-0.43	76	77
DOK1	0.027	0.002	-10000	0	-10000	0	0
MATK	-0.083	0.19	-10000	0	-0.47	79	79
CREBBP	0.014	0.06	-10000	0	-10000	0	0
BCL2	-0.18	0.41	-10000	0	-1.2	50	50

×

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	0.023	0.04	-10000	0	-0.4	4	4
LAT2	-0.093	0.16	-10000	0	-0.32	112	112
AP1	-0.12	0.24	-10000	0	-0.52	97	97
mol:PIP3	-0.12	0.2	0.22	5	-0.46	84	89
IKBKB	-0.072	0.14	0.18	23	-0.28	94	117
AKT1	-0.088	0.12	0.29	6	-0.33	43	49
IKBKG	-0.084	0.13	0.19	5	-0.28	102	107
MS4A2	-0.098	0.19	-10000	0	-0.4	130	130
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.026	0.003	-10000	0	-10000	0	0
MAP3K1	-0.11	0.18	0.23	2	-0.41	84	86
mol:Ca2+	-0.093	0.15	0.2	5	-0.34	83	88
LYN	0.022	0.011	-10000	0	-10000	0	0
CBLB	-0.092	0.16	-10000	0	-0.32	110	110
SHC1	0.027	0.004	-10000	0	-10000	0	0
RasGAP/p62DOK	0.05	0.021	-10000	0	-0.21	2	2
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
PLD2	-0.093	0.14	0.32	6	-0.36	61	67
PTPN13	-0.1	0.19	-10000	0	-0.61	21	21
PTPN11	0.014	0.025	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.079	0.12	0.2	3	-0.3	46	49
SYK	0.025	0.008	-10000	0	-10000	0	0
GRB2	0.026	0.004	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.21	-10000	0	-0.47	86	86
LAT	-0.094	0.16	-10000	0	-0.37	76	76
PAK2	-0.12	0.2	0.24	2	-0.45	89	91
NFATC2	-0.035	0.099	-10000	0	-0.56	12	12
HRAS	-0.13	0.22	0.23	4	-0.49	90	94
GAB2	0.027	0.003	-10000	0	-10000	0	0
PLA2G1B	0.021	0.11	-10000	0	-0.89	6	6
Fc epsilon R1	-0.099	0.19	-10000	0	-0.3	189	189
Antigen/IgE/Fc epsilon R1	-0.088	0.17	-10000	0	-0.28	182	182
mol:GDP	-0.14	0.24	0.24	2	-0.53	98	100
JUN	0.027	0.005	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
FOS	0.023	0.035	-10000	0	-0.4	3	3
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.094	0.16	-10000	0	-0.33	116	116
CHUK	-0.084	0.13	0.16	4	-0.28	103	107
KLRG1	-0.083	0.14	-10000	0	-0.34	71	71
VAV1	-0.1	0.17	-10000	0	-0.38	86	86
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.093	0.16	-10000	0	-0.37	77	77
negative regulation of mast cell degranulation	-0.068	0.14	-10000	0	-0.33	69	69
BTK	-0.16	0.27	-10000	0	-0.59	101	101
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.14	0.22	-10000	0	-0.52	90	90
GAB2/PI3K/SHP2	-0.1	0.12	-10000	0	-0.34	57	57
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.09	0.16	-10000	0	-0.41	68	68
RAF1	0.025	0.12	-10000	0	-0.96	6	6
Fc epsilon R1/FcgammaRIIB/SHIP	-0.088	0.21	-10000	0	-0.44	83	83
FCER1G	0.027	0.047	-10000	0	-0.4	5	5
FCER1A	-0.099	0.19	-10000	0	-0.41	126	126
Antigen/IgE/Fc epsilon R1/Fyn	-0.074	0.17	-10000	0	-0.3	118	118
MAPK3	0.022	0.11	-10000	0	-0.88	6	6
MAPK1	0.017	0.12	-10000	0	-0.92	6	6
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.11	0.27	-10000	0	-0.69	69	69
DUSP1	0.025	0.028	-10000	0	-0.4	2	2
NF-kappa-B/RelA	-0.043	0.083	-10000	0	-0.2	40	40
actin cytoskeleton reorganization	-0.098	0.19	-10000	0	-0.58	21	21
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.099	0.2	0.28	2	-0.44	78	80
FER	-0.088	0.16	-10000	0	-0.32	107	107
RELA	0.027	0.004	-10000	0	-10000	0	0
ITK	-0.035	0.096	-10000	0	-0.38	25	25
SOS1	0.027	0.002	-10000	0	-10000	0	0
PLCG1	-0.092	0.24	0.24	8	-0.49	87	95
cytokine secretion	-0.033	0.058	-10000	0	-10000	0	0
SPHK1	-0.11	0.16	-10000	0	-0.35	97	97
PTK2	-0.1	0.19	-10000	0	-0.62	20	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.22	0.21	6	-0.48	87	93
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.12	0.2	0.23	4	-0.45	86	90
MAP2K2	0.017	0.11	-10000	0	-0.88	6	6
MAP2K1	0.017	0.11	-10000	0	-0.9	6	6
MAP2K7	0.026	0.02	-10000	0	-0.4	1	1
KLRG1/SHP2	-0.065	0.13	0.18	2	-0.32	60	62
MAP2K4	-0.15	0.38	-10000	0	-0.91	88	88
Fc epsilon R1/FcgammaRIIB	-0.1	0.21	-10000	0	-0.36	143	143
mol:Choline	-0.092	0.14	0.32	6	-0.36	61	67
SHC/Grb2/SOS1	-0.063	0.17	-10000	0	-0.37	69	69
FYN	0.027	0.004	-10000	0	-10000	0	0
DOK1	0.027	0.002	-10000	0	-10000	0	0
PXN	-0.096	0.18	-10000	0	-0.57	20	20
HCLS1	-0.094	0.16	-10000	0	-0.33	110	110
PRKCB	-0.12	0.18	0.19	3	-0.39	108	111
FCGR2B	-0.021	0.13	-10000	0	-0.4	51	51
IGHE	-0.003	0.005	-10000	0	-10000	0	0
KLRG1/SHIP	-0.07	0.15	-10000	0	-0.34	69	69
LCP2	0.023	0.04	-10000	0	-0.4	4	4
PLA2G4A	-0.11	0.18	-10000	0	-0.35	132	132
RASA1	0.027	0.005	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.092	0.14	0.32	6	-0.36	61	67
IKK complex	-0.051	0.11	0.17	25	-0.23	55	80
WIPF1	0.025	0.034	-10000	0	-0.4	3	3

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.039	0.009	-10000	0	-10000	0	0
Necdin/E2F1	0.018	0.06	0.26	6	-0.28	12	18
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.01	0.13	-10000	0	-0.38	9	9
NGF (dimer)/p75(NTR)/BEX1	-0.1	0.18	-10000	0	-0.29	196	196
NT-4/5 (dimer)/p75(NTR)	-0.059	0.15	-10000	0	-0.29	128	128
IKBKB	0.024	0.009	-10000	0	-10000	0	0
AKT1	-0.048	0.1	-10000	0	-0.38	7	7
IKBKG	0.026	0.02	-10000	0	-0.4	1	1
BDNF	0.014	0.076	-10000	0	-0.43	13	13
MGDIs/NGR/p75(NTR)/LINGO1	-0.046	0.15	-10000	0	-0.25	142	142
FURIN	0.025	0.021	-10000	0	-0.4	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.03	0.13	-10000	0	-0.24	126	126
LINGO1	0.005	0.096	-10000	0	-0.43	21	21
Sortilin/TRAF6/NRIF	0.03	0.028	-10000	0	-10000	0	0
proBDNF (dimer)	0.014	0.076	-10000	0	-0.43	13	13
NTRK1	0.018	0.044	-10000	0	-0.43	4	4
RTN4R	0.009	0.087	-10000	0	-0.43	17	17
neuron apoptosis	-0.058	0.14	0.3	3	-0.39	34	37
IRAK1	0.027	0.003	-10000	0	-10000	0	0
SHC1	-0.054	0.12	-10000	0	-0.25	117	117
ARHGDIA	0.026	0.02	-10000	0	-0.4	1	1
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.07	0.032	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.016	0.14	-10000	0	-0.23	118	118
MAGEH1	0.022	0.049	-10000	0	-0.4	6	6
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.022	0.14	-10000	0	-0.24	112	112
Mammalian IAPs/DIABLO	0.063	0.04	-10000	0	-0.22	8	8
proNGF (dimer)	0.008	0.079	-10000	0	-0.4	16	16
MAGED1	0.027	0.003	-10000	0	-10000	0	0
APP	0.026	0.006	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.018	0.091	-10000	0	-0.44	19	19
ZNF274	0.023	0.04	-10000	0	-0.4	4	4
RhoA/GDP/RHOGDI	-0.03	0.11	-10000	0	-0.21	111	111
NGF	0.008	0.079	-10000	0	-0.4	16	16
cell cycle arrest	-0.038	0.1	0.22	3	-0.34	8	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.036	0.11	-10000	0	-0.32	15	15
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.036	0.14	-10000	0	-0.25	128	128
NCSTN	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	-0.061	0.16	-10000	0	-0.27	154	154
PSENEN	0.026	0.02	-10000	0	-0.4	1	1
mol:ceramide	-0.048	0.11	0.18	2	-0.38	8	10
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.03	0.095	-10000	0	-0.32	16	16
p75(NTR)/beta APP	-0.042	0.14	-10000	0	-0.28	114	114
BEX1	-0.099	0.18	-10000	0	-0.4	124	124
mol:GDP	-0.07	0.11	-10000	0	-0.24	122	122
NGF (dimer)	-0.27	0.11	-10000	0	-0.28	429	429
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.03	0.14	-10000	0	-0.23	135	135
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RAC1/GTP	-0.024	0.11	-10000	0	-0.21	115	115
MYD88	0.027	0.003	-10000	0	-10000	0	0
CHUK	0.026	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.061	0.16	-10000	0	-0.27	154	154
RHOB	0.027	0.001	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.026	0.042	0.26	7	-0.3	2	9
NT3 (dimer)	0.018	0.056	-10000	0	-0.4	8	8
TP53	-0.058	0.093	0.35	3	-0.38	3	6
PRDM4	-0.049	0.11	0.18	2	-0.38	8	10
BDNF (dimer)	-0.44	0.14	0.38	1	-0.45	442	443
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
SORT1	0.026	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.013	0.12	-10000	0	-0.38	9	9
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.014	0.13	-10000	0	-0.23	115	115
RHOC	0.026	0.006	-10000	0	-10000	0	0
XIAP	0.027	0.002	-10000	0	-10000	0	0
MAPK10	-0.077	0.16	0.32	4	-0.44	42	46
DIABLO	0.027	0.003	-10000	0	-10000	0	0
SMPD2	-0.049	0.11	0.18	2	-0.38	8	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	-0.029	0.14	-10000	0	-0.25	118	118
PSEN1	0.025	0.007	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.011	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.046	0.14	-10000	0	-0.28	117	117
MAPK8	-0.053	0.13	0.35	3	-0.36	15	18
MAPK9	-0.052	0.13	0.35	3	-0.37	14	17
APAF1	0.027	0.003	-10000	0	-10000	0	0
NTF3	0.018	0.056	-10000	0	-0.4	8	8
NTF4	-0.018	0.091	-10000	0	-0.44	19	19
NDN	0.011	0.076	-10000	0	-0.4	15	15
RAC1/GDP	0.018	0.006	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.032	0.14	-10000	0	-0.37	27	27
p75 CTF/Sortilin/TRAF6/NRIF	0.064	0.029	-10000	0	-0.21	3	3
RhoA-B-C/GTP	-0.061	0.16	-10000	0	-0.27	154	154
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.006	0.13	-10000	0	-0.26	15	15
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.014	0.13	-10000	0	-0.22	121	121
PRKACB	-0.026	0.14	-10000	0	-0.4	56	56
proBDNF (dimer)/p75 ECD	0.03	0.058	-10000	0	-0.3	13	13
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.019	0.057	-10000	0	-0.4	8	8
BIRC2	0.027	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.06	0.13	-10000	0	-0.3	59	59
BAD	-0.07	0.15	0.29	5	-0.36	41	46
RIPK2	0.023	0.01	-10000	0	-10000	0	0
NGFR	-0.081	0.18	-10000	0	-0.4	114	114
CYCS	-0.046	0.1	-10000	0	-0.38	7	7
ADAM17	0.027	0.002	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.014	0.12	-10000	0	-0.22	100	100
BCL2L11	-0.069	0.15	0.29	5	-0.36	41	46
BDNF (dimer)/p75(NTR)	-0.051	0.15	-10000	0	-0.28	126	126
PI3K	-0.013	0.13	-10000	0	-0.23	110	110
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.014	0.13	-10000	0	-0.23	106	106
NDNL2	0.026	0.007	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
PRKCI	0.025	0.028	-10000	0	-0.4	2	2
NGF (dimer)/p75(NTR)	-0.052	0.15	-10000	0	-0.29	122	122
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.012	0.13	-10000	0	-0.23	112	112
TRAF6	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
PLG	-0.083	0.17	-10000	0	-0.43	83	83
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.057	0.12	-10000	0	-0.25	110	110
SQSTM1	0.027	0.003	-10000	0	-10000	0	0
NGFRAP1	0.025	0.028	-10000	0	-0.4	2	2
CASP3	-0.068	0.14	0.3	4	-0.34	43	47
E2F1	0.021	0.056	0.36	8	-0.43	2	10
CASP9	0.026	0.007	-10000	0	-10000	0	0
IKK complex	-0.003	0.11	-10000	0	-0.37	10	10
NGF (dimer)/TRKA	0.023	0.067	-10000	0	-0.29	20	20
MMP7	-0.41	0.11	0.36	3	-0.43	429	432
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.005	0.13	-10000	0	-0.39	9	9
MMP3	-0.34	0.18	0.36	1	-0.43	366	367
APAF-1/Caspase 9	-0.037	0.091	-10000	0	-0.32	10	10

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.27	0.27	-10000	0	-0.79	46	46
PCK1	-0.61	0.6	-10000	0	-1.2	203	203
HNF4A	-0.25	0.28	-10000	0	-0.88	34	34
KCNJ11	-0.28	0.28	-10000	0	-0.84	41	41
AKT1	-0.2	0.17	-10000	0	-0.54	36	36
response to starvation	-0.016	0.027	-10000	0	-10000	0	0
DLK1	-0.29	0.29	-10000	0	-0.82	53	53
NKX2-1	-0.12	0.14	0.3	7	-0.36	36	43
ACADM	-0.28	0.27	-10000	0	-0.79	52	52
TAT	-0.61	0.58	-10000	0	-1.3	180	180
CEBPB	0.004	0.032	-10000	0	-10000	0	0
CEBPA	0.001	0.055	-10000	0	-0.4	3	3
TTR	-0.31	0.45	0.52	1	-1.1	88	89
PKLR	-0.34	0.34	-10000	0	-0.91	87	87
APOA1	-0.29	0.31	-10000	0	-0.94	35	35
CPT1C	-0.28	0.27	-10000	0	-0.79	51	51
ALAS1	-0.14	0.15	-10000	0	-0.52	9	9
TFRC	-0.28	0.23	-10000	0	-0.66	45	45
FOXF1	0.019	0.059	-10000	0	-0.4	9	9
NF1	0.031	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	-0.075	0.057	-10000	0	-0.28	8	8
CPT1A	-0.28	0.27	-10000	0	-0.78	50	50
HMGCS1	-0.28	0.27	-10000	0	-0.78	51	51
NR3C1	-0.079	0.13	-10000	0	-0.3	81	81
CPT1B	-0.28	0.27	-10000	0	-0.78	51	51
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.062	0.037	-10000	0	-10000	0	0
GCK	-0.28	0.28	-10000	0	-0.81	57	57
CREB1	-0.072	0.1	-10000	0	-0.22	91	91
IGFBP1	-0.21	0.19	-10000	0	-0.58	40	40
PDX1	-0.29	0.18	-10000	0	-0.56	57	57
UCP2	-0.28	0.27	-10000	0	-0.78	50	50
ALDOB	-0.32	0.32	-10000	0	-0.87	75	75
AFP	-0.12	0.13	-10000	0	-0.4	53	53
BDH1	-0.28	0.27	-10000	0	-0.79	50	50
HADH	-0.28	0.28	-10000	0	-0.83	41	41
F2	-0.31	0.32	-10000	0	-0.95	39	39
HNF1A	-0.075	0.057	-10000	0	-0.28	8	8
G6PC	-0.22	0.39	-10000	0	-1.2	57	57
SLC2A2	-0.21	0.18	-10000	0	-0.74	8	8
INS	-0.006	0.039	-10000	0	-10000	0	0
FOXA1	-0.034	0.12	-10000	0	-0.35	47	47
FOXA3	-0.16	0.14	-10000	0	-0.34	92	92
FOXA2	-0.32	0.32	-10000	0	-0.85	68	68
ABCC8	-0.33	0.34	-10000	0	-0.94	72	72
ALB	-0.12	0.14	-10000	0	-0.4	57	57

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.4	0.28	-9999	-0.86	70	70
HDAC7	0.027	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.32	0.25	-9999	-0.8	35	35
SMAD4	0.021	0.012	-9999	-10000	0	0
ID2	-0.4	0.29	-9999	-0.87	66	66
AP1	0.036	0.028	-9999	-0.27	3	3
ABCG2	-0.55	0.32	-9999	-0.87	163	163
HIF1A	-0.075	0.054	-9999	-10000	0	0
TFF3	-0.41	0.3	-9999	-0.89	67	67
GATA2	0.018	0.066	-9999	-0.4	11	11
AKT1	-0.075	0.058	-9999	-0.25	4	4
response to hypoxia	-0.078	0.049	-9999	-0.22	10	10
MCL1	-0.4	0.29	-9999	-0.87	66	66
NDRG1	-0.38	0.29	-9999	-0.88	61	61
SERPINE1	-0.44	0.32	-9999	-0.88	91	91
FECH	-0.4	0.29	-9999	-0.87	66	66
FURIN	-0.4	0.29	-9999	-0.87	67	67
NCOA2	0.023	0.022	-9999	-0.4	1	1
EP300	-0.071	0.078	-9999	-0.3	26	26
HMOX1	-0.4	0.3	-9999	-0.88	69	69
BHLHE40	-0.4	0.29	-9999	-0.88	68	68
BHLHE41	-0.4	0.3	-9999	-0.89	68	68
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.071	0.087	-9999	-10000	0	0
ENG	-0.075	0.07	-9999	-10000	0	0
JUN	0.027	0.006	-9999	-10000	0	0
RORA	-0.4	0.3	-9999	-0.88	69	69
ABCB1	-0.28	0.43	-9999	-1.1	94	94
TFRC	-0.4	0.29	-9999	-0.87	66	66
CXCR4	-0.4	0.29	-9999	-0.87	66	66
TF	-0.42	0.31	-9999	-0.9	78	78
CITED2	-0.4	0.29	-9999	-0.87	66	66
HIF1A/ARNT	-0.44	0.33	-9999	-0.97	66	66
LDHA	-0.039	0.066	-9999	-0.77	2	2
ETS1	-0.4	0.29	-9999	-0.87	66	66
PGK1	-0.4	0.29	-9999	-0.87	66	66
NOS2	-0.41	0.3	-9999	-0.88	72	72
ITGB2	-0.4	0.3	-9999	-0.88	69	69
ALDOA	-0.4	0.29	-9999	-0.87	65	65
Cbp/p300/CITED2	-0.4	0.3	-9999	-0.98	44	44
FOS	0.023	0.035	-9999	-0.4	3	3
HK2	-0.4	0.29	-9999	-0.87	66	66
SP1	0.005	0.055	-9999	-10000	0	0
GCK	-0.095	0.2	-9999	-1.3	9	9
HK1	-0.4	0.29	-9999	-0.87	65	65
NPM1	-0.4	0.29	-9999	-0.87	66	66
EGLN1	-0.4	0.29	-9999	-0.87	66	66
CREB1	0.033	0	-9999	-10000	0	0
PGM1	-0.4	0.29	-9999	-0.86	70	70
SMAD3	0.026	0.007	-9999	-10000	0	0
EDN1	-0.079	0.14	-9999	-0.7	10	10
IGFBP1	-0.42	0.31	-9999	-0.9	78	78
VEGFA	-0.29	0.21	-9999	-0.77	20	20
HIF1A/JAB1	-0.038	0.045	-9999	-10000	0	0
CP	-0.48	0.33	-9999	-0.88	128	128
CXCL12	-0.43	0.32	-9999	-0.89	94	94
COPS5	0.024	0.01	-9999	-10000	0	0
SMAD3/SMAD4	0.031	0.019	-9999	-10000	0	0
BNIP3	-0.4	0.3	-9999	-0.88	67	67
EGLN3	-0.4	0.29	-9999	-0.87	67	67
CA9	-0.53	0.32	-9999	-0.88	144	144
TERT	-0.42	0.31	-9999	-0.89	76	76
ENO1	-0.4	0.29	-9999	-0.87	66	66
PFKL	-0.4	0.29	-9999	-0.87	67	67
NCOA1	0.028	0.001	-9999	-10000	0	0
ADM	-0.4	0.29	-9999	-0.87	66	66
ARNT	-0.08	0.054	-9999	-0.45	1	1
HNF4A	0.016	0.019	-9999	-10000	0	0
ADFP	-0.4	0.28	-9999	-0.86	70	70
SLC2A1	-0.29	0.22	-9999	-0.75	33	33
LEP	-0.41	0.3	-9999	-0.9	72	72
HIF1A/ARNT/Cbp/p300	-0.33	0.25	-9999	-0.8	42	42
EPO	-0.22	0.18	-9999	-0.77	9	9
CREBBP	-0.07	0.075	-9999	-0.3	22	22
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.25	-9999	-0.86	28	28
PFKFB3	-0.4	0.29	-9999	-0.87	66	66
NT5E	-0.4	0.29	-9999	-0.88	68	68

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.02	0.079	-10000	0	-0.4	12	12
Crk/p130 Cas/Paxillin	-0.094	0.12	-10000	0	-0.33	42	42
JUN	-0.087	0.13	-10000	0	-0.35	51	51
HRAS	0.026	0.02	-10000	0	-0.4	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.072	0.16	-10000	0	-0.4	39	39
RAP1A	0.026	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	-0.074	0.17	-10000	0	-0.39	46	46
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.003	-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	-0.047	0.13	-10000	0	-0.21	158	158
RHOA	0.027	0.004	-10000	0	-10000	0	0
RAP1A/GTP	-0.066	0.15	-10000	0	-0.37	41	41
GRB7	0.033	0.044	0.36	8	-10000	0	8
RET51/GFRalpha1/GDNF	-0.074	0.17	-10000	0	-0.39	47	47
MAPKKK cascade	-0.085	0.15	-10000	0	-0.4	40	40
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.047	0.13	-10000	0	-0.21	160	160
lamellipodium assembly	-0.081	0.12	-10000	0	-0.26	80	80
RET51/GFRalpha1/GDNF/SHC	-0.074	0.17	-10000	0	-0.4	44	44
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.046	0.12	-10000	0	-0.21	158	158
RET9/GFRalpha1/GDNF/Shank3	-0.048	0.13	-10000	0	-0.21	162	162
MAPK3	-0.1	0.12	-10000	0	-0.36	42	42
DOK1	0.027	0.002	-10000	0	-10000	0	0
DOK6	0.013	0.053	-10000	0	-0.4	7	7
PXN	0.027	0.002	-10000	0	-10000	0	0
neurite development	-0.074	0.11	-10000	0	-0.36	25	25
DOK5	0.011	0.052	0.36	1	-0.4	6	7
GFRA1	-0.13	0.2	-10000	0	-0.4	166	166
MAPK8	-0.091	0.14	-10000	0	-0.36	53	53
HRAS/GTP	-0.085	0.18	-10000	0	-0.43	45	45
tube development	-0.044	0.12	0.21	1	-0.21	66	67
MAPK1	-0.099	0.12	-10000	0	-0.36	41	41
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.058	0.11	-10000	0	-0.2	158	158
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
SRC	0.017	0.013	-10000	0	-10000	0	0
PDLIM7	0.027	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.055	0.14	-10000	0	-0.4	26	26
SHC1	0.027	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.074	0.17	-10000	0	-0.38	48	48
RET51/GFRalpha1/GDNF/Dok5	-0.059	0.14	0.26	1	-0.28	83	84
PRKCA	0.026	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
CREB1	-0.091	0.15	-10000	0	-0.28	160	160
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.058	0.11	-10000	0	-0.21	156	156
RET51/GFRalpha1/GDNF/Grb7	-0.069	0.17	0.26	4	-0.29	100	104
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.041	0.16	-10000	0	-0.4	72	72
DOK4	0.026	0.02	-10000	0	-0.4	1	1
JNK cascade	-0.086	0.13	-10000	0	-0.34	51	51
RET9/GFRalpha1/GDNF/FRS2	-0.047	0.13	-10000	0	-0.21	161	161
SHANK3	0.025	0.021	-10000	0	-0.4	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.057	0.11	-10000	0	-0.21	156	156
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.09	0.14	-10000	0	-0.39	46	46
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.091	0.15	-10000	0	-0.38	55	55
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.097	0.16	-10000	0	-0.47	47	47
PI3K	-0.12	0.18	-10000	0	-0.36	135	135
SOS1	0.027	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.035	0.12	-10000	0	-0.21	66	66
GRB10	0.025	0.008	-10000	0	-10000	0	0
activation of MAPKK activity	-0.075	0.13	-10000	0	-0.33	42	42
RET51/GFRalpha1/GDNF/FRS2	-0.074	0.17	-10000	0	-0.39	47	47
GAB1	0.027	0.005	-10000	0	-10000	0	0
IRS1	0.027	0.002	-10000	0	-10000	0	0
IRS2	0.021	0.012	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.098	0.16	-10000	0	-0.46	49	49
RET51/GFRalpha1/GDNF/PKC alpha	-0.073	0.16	-10000	0	-0.29	99	99
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GDNF	0.014	0.02	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.074	0.17	-10000	0	-0.39	47	47
Rac1/GTP	-0.092	0.14	-10000	0	-0.36	43	43
RET9/GFRalpha1/GDNF	-0.064	0.13	-10000	0	-0.24	162	162
GFRalpha1/GDNF	-0.078	0.15	-10000	0	-0.28	162	162

×

Visual signal transduction: Rods

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
mol:K +	0.026	0.006	-10000	0	-10000	0	0
GNAT1/GTP	0.013	0.002	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.023	0.023	-10000	0	-0.26	3	3
PDE6G/GNAT1/GTP	0.011	0.067	-10000	0	-0.24	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.018	0.003	-10000	0	-10000	0	0
GRK1	-0.011	0.031	-10000	0	-0.43	2	2
CNG Channel	-0.16	0.17	-10000	0	-0.41	86	86
mol:Na +	-0.03	0.13	-10000	0	-0.4	20	20
mol:ADP	-0.011	0.031	-10000	0	-0.43	2	2
RGS9-1/Gbeta5/R9AP	0.007	0.1	0.25	1	-0.24	67	68
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.025	0.13	-10000	0	-0.42	20	20
CNGB1	-0.048	0.13	-10000	0	-0.4	56	56
RDH5	-0.011	0.12	-10000	0	-0.4	41	41
SAG	-0.009	0.018	-10000	0	-10000	0	0
mol:Ca2+	-0.066	0.11	0.3	7	-0.39	20	27
Na + (4 Units)	-0.032	0.12	-10000	0	-0.38	20	20
RGS9	-0.037	0.15	-10000	0	-0.4	67	67
GNB1/GNGT1	-0.045	0.15	0.26	11	-0.3	113	124
GNAT1/GDP	0.013	0.093	0.23	1	-0.2	67	68
GUCY2D	-0.004	0.083	-10000	0	-0.43	16	16
GNGT1	-0.09	0.2	0.36	12	-0.43	113	125
GUCY2F	-0.016	0.022	-10000	0	-0.43	1	1
GNB5	0.026	0.006	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.13	0.13	-10000	0	-0.23	272	272
mol:11-cis-retinal	-0.011	0.12	-10000	0	-0.4	41	41
mol:cGMP	0.018	0.079	-10000	0	-0.26	29	29
GNB1	0.026	0.007	-10000	0	-10000	0	0
Rhodopsin	0.002	0.095	-10000	0	-0.28	44	44
SLC24A1	0.026	0.006	-10000	0	-10000	0	0
CNGA1	-0.016	0.13	-10000	0	-0.4	45	45
Metarhodopsin II	0.016	0.031	-10000	0	-0.28	4	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.027	0.084	-10000	0	-0.26	31	31
RGS9BP	0.021	0.031	0.36	1	-0.43	1	2
Metarhodopsin II/Transducin	-0.019	0.065	0.15	10	-0.22	11	21
GCAP Family/Ca ++	0.032	0.056	-10000	0	-0.24	18	18
PDE6A/B	-0.16	0.17	-10000	0	-0.29	267	267
mol:Pi	0.007	0.1	0.25	1	-0.23	67	68
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.025	0.13	0.23	11	-0.23	113	124
PDE6B	0.006	0.087	-10000	0	-0.4	20	20
PDE6A	-0.22	0.21	-10000	0	-0.4	263	263
PDE6G	-0.002	0.1	-10000	0	-0.4	30	30
RHO	-0.017	0.036	-10000	0	-0.43	3	3
PDE6	-0.14	0.17	-10000	0	-0.41	66	66
GUCA1A	-0.001	0.088	0.36	1	-0.43	17	18
GC2/GCAP Family	0.042	0.062	-10000	0	-0.26	18	18
GUCA1C	-0.018	0.002	-10000	0	-10000	0	0
GUCA1B	0.027	0.031	0.36	2	-0.43	1	3

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.012	0.16	0.26	58	-0.42	12	70
SMAD6-7/SMURF1	0.04	0.028	-10000	0	-0.24	1	1
NOG	0.014	0.029	-10000	0	-0.43	1	1
SMAD9	-0.05	0.18	-10000	0	-0.56	47	47
SMAD4	0.02	0.012	-10000	0	-10000	0	0
SMAD5	-0.039	0.13	-10000	0	-0.39	35	35
BMP7/USAG1	-0.057	0.2	0.26	56	-0.34	132	188
SMAD5/SKI	-0.039	0.14	-10000	0	-0.4	34	34
SMAD1	0.01	0.049	-10000	0	-0.41	1	1
BMP2	0.006	0.083	-10000	0	-0.4	18	18
SMAD1/SMAD1/SMAD4	0.02	0.061	-10000	0	-0.37	4	4
BMPR1A	0.026	0.006	-10000	0	-10000	0	0
BMPR1B	-0.01	0.11	-10000	0	-0.42	32	32
BMPR1A-1B/BAMBI	0.009	0.1	-10000	0	-0.25	62	62
AHSG	-0.05	0.16	0.36	2	-0.43	64	66
CER1	-0.018	0.085	0.36	1	-0.43	17	18
BMP2-4/CER1	0.001	0.1	-10000	0	-0.26	54	54
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.042	0.13	-10000	0	-0.36	37	37
BMP2-4 (homodimer)	0.002	0.098	-10000	0	-0.3	40	40
RGMB	0.026	0.006	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.024	0.1	-10000	0	-0.23	57	57
RGMA	-0.06	0.17	-10000	0	-0.4	92	92
SMURF1	0.026	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.04	0.12	-10000	0	-0.37	35	35
BMP2-4/USAG1	-0.03	0.13	-10000	0	-0.27	99	99
SMAD6/SMURF1/SMAD5	-0.039	0.14	-10000	0	-0.4	35	35
SOSTDC1	-0.052	0.16	-10000	0	-0.4	80	80
BMP7/BMPR2/BMPR1A-1B	-0.008	0.16	0.26	64	-0.24	113	177
SKI	0.026	0.007	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.002	0.11	-10000	0	-0.4	31	31
HFE2	-0.008	0.027	-10000	0	-0.43	1	1
ZFYVE16	0.025	0.028	-10000	0	-0.4	2	2
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	0.015	0.09	-10000	0	-0.26	41	41
SMAD5/SMAD5/SMAD4	-0.036	0.13	-10000	0	-0.4	31	31
MAPK1	0.026	0.006	-10000	0	-10000	0	0
TAK1/TAB family	-0.028	0.12	-10000	0	-0.34	31	31
BMP7 (homodimer)	-0.029	0.25	0.36	75	-0.42	105	180
NUP214	0.027	0.003	-10000	0	-10000	0	0
BMP6/FETUA	-0.031	0.14	-10000	0	-0.31	87	87
SMAD1/SKI	0.014	0.074	-10000	0	-0.43	5	5
SMAD6	0.026	0.006	-10000	0	-10000	0	0
CTDSP2	0.027	0.002	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.022	0.13	0.25	1	-0.27	89	90
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.002	0.098	-10000	0	-0.41	24	24
BMPR2 (homodimer)	0.026	0.02	-10000	0	-0.4	1	1
GADD34/PP1CA	0.051	0.023	-10000	0	-0.24	2	2
BMPR1A-1B (homodimer)	0.013	0.086	-10000	0	-0.29	32	32
CHRDL1	-0.2	0.21	-10000	0	-0.4	239	239
ENDOFIN/SMAD1	0.014	0.076	-10000	0	-0.44	5	5
SMAD6-7/SMURF1/SMAD1	0.031	0.074	-10000	0	-0.4	5	5
SMAD6/SMURF1	0.026	0.006	-10000	0	-10000	0	0
BAMBI	-0.004	0.12	-10000	0	-0.43	31	31
SMURF2	0.026	0.021	-10000	0	-0.4	1	1
BMP2-4/CHRDL1	-0.11	0.16	-10000	0	-0.26	224	224
BMP2-4/GREM1	-0.001	0.11	-10000	0	-0.26	61	61
SMAD7	0.02	0.023	-10000	0	-0.4	1	1
SMAD8A/SMAD8A/SMAD4	-0.048	0.19	-10000	0	-0.5	58	58
SMAD1/SMAD6	0.013	0.076	-10000	0	-0.44	5	5
TAK1/SMAD6	0.038	0.01	-10000	0	-10000	0	0
BMP7	-0.029	0.25	0.36	75	-0.42	105	180
BMP6	-0.002	0.11	-10000	0	-0.4	31	31
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.047	0.14	-10000	0	-0.39	44	44
PPM1A	0.026	0.007	-10000	0	-10000	0	0
SMAD1/SMURF2	0.015	0.075	-10000	0	-0.44	5	5
SMAD7/SMURF1	0.029	0.023	-10000	0	-0.28	1	1
CTDSPL	0.027	0.003	-10000	0	-10000	0	0
PPP1CA	0.027	0.004	-10000	0	-10000	0	0
XIAP	0.027	0.002	-10000	0	-10000	0	0
CTDSP1	0.027	0.001	-10000	0	-10000	0	0
PPP1R15A	0.027	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.055	0.15	-10000	0	-0.4	55	55
CHRD	0.026	0.02	-10000	0	-0.4	1	1
BMPR2	0.026	0.02	-10000	0	-0.4	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.048	0.13	-10000	0	-0.36	46	46
BMP4	0	0.1	-10000	0	-0.42	26	26
FST	0.009	0.084	-10000	0	-0.4	18	18
BMP2-4/NOG	0.013	0.091	-10000	0	-0.26	41	41
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.005	0.16	0.26	58	-0.41	7	65

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.013	0.099	-10000	0	-0.49	9	9
IHH	0.019	0.085	-10000	0	-0.45	13	13
SHH Np/Cholesterol/GAS1	-0.049	0.13	0.19	2	-0.25	121	123
LRPAP1	0.027	0.005	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.049	0.13	0.25	121	-0.18	2	123
SMO/beta Arrestin2	0.018	0.09	-10000	0	-0.48	5	5
SMO	0.006	0.085	-10000	0	-0.51	5	5
AKT1	0.002	0.11	-10000	0	-0.4	13	13
ARRB2	0.023	0.01	-10000	0	-10000	0	0
BOC	0.019	0.059	-10000	0	-0.4	9	9
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
heart looping	0.007	0.085	-10000	0	-0.5	5	5
STIL	-0.017	0.11	-10000	0	-0.37	7	7
DHH N/PTCH2	0.025	0.066	-10000	0	-0.28	20	20
DHH N/PTCH1	0.021	0.091	-10000	0	-0.46	6	6
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
DHH	0.006	0.085	-10000	0	-0.4	19	19
PTHLH	0.008	0.13	-10000	0	-0.74	9	9
determination of left/right symmetry	0.007	0.085	-10000	0	-0.5	5	5
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
skeletal system development	0.008	0.13	-10000	0	-0.74	9	9
IHH N/Hhip	-0.039	0.15	-10000	0	-0.32	100	100
DHH N/Hhip	-0.039	0.15	-10000	0	-0.3	101	101
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.007	0.085	-10000	0	-0.5	5	5
pancreas development	-0.062	0.17	-10000	0	-0.4	93	93
HHAT	0.023	0.04	-10000	0	-0.4	4	4
PI3K	0.039	0.008	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.033	0.15	-10000	0	-0.4	63	63
somite specification	0.007	0.085	-10000	0	-0.5	5	5
SHH Np/Cholesterol/PTCH1	-0.018	0.11	-10000	0	-0.36	9	9
SHH Np/Cholesterol/PTCH2	-0.02	0.1	0.19	4	-0.23	82	86
SHH Np/Cholesterol/Megalin	-0.042	0.12	0.18	4	-0.25	110	114
SHH	-0.041	0.12	0.27	4	-0.3	80	84
catabolic process	0.018	0.077	-10000	0	-0.4	8	8
SMO/Vitamin D3	-0.014	0.11	-10000	0	-0.44	6	6
SHH Np/Cholesterol/Hhip	-0.063	0.13	0.18	4	-0.23	155	159
LRP2	-0.033	0.12	-10000	0	-0.43	40	40
receptor-mediated endocytosis	-0.028	0.11	-10000	0	-0.41	10	10
SHH Np/Cholesterol/BOC	-0.023	0.1	0.19	3	-0.23	86	89
SHH Np/Cholesterol/CDO	-0.019	0.1	0.19	3	-0.23	81	84
mesenchymal cell differentiation	0.063	0.13	0.23	155	-0.18	4	159
mol:Vitamin D3	-0.012	0.11	-10000	0	-0.36	9	9
IHH N/PTCH2	0.031	0.058	-10000	0	-0.27	14	14
CDON	0.027	0.004	-10000	0	-10000	0	0
IHH N/PTCH1	0.026	0.08	-10000	0	-0.4	8	8
Megalin/LRPAP1	0.005	0.097	-10000	0	-0.3	40	40
PTCH2	0.025	0.022	-10000	0	-0.43	1	1
SHH Np/Cholesterol	-0.029	0.094	-10000	0	-0.23	81	81
PTCH1	0.018	0.078	-10000	0	-0.4	8	8
HHIP	-0.062	0.17	-10000	0	-0.4	93	93

×

Syndecan-1-mediated signaling events

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
TGFB1	0.026	0.022	-10000	0	-0.43	1	1
CCL5	0.009	0.085	-10000	0	-0.4	19	19
SDCBP	0.023	0.022	-10000	0	-0.4	1	1
FGFR/FGF2/Syndecan-1	-0.11	0.099	0.3	3	-0.29	31	34
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	-0.084	0.099	0.23	3	-0.35	12	15
Syndecan-1/Syntenin	-0.097	0.098	0.28	2	-0.37	12	14
MAPK3	-0.1	0.092	0.26	2	-0.38	9	11
HGF/MET	0.029	0.056	-10000	0	-0.29	13	13
TGFB1/TGF beta receptor Type II	0.026	0.022	-10000	0	-0.43	1	1
BSG	0.026	0.02	-10000	0	-0.4	1	1
keratinocyte migration	-0.084	0.098	0.23	3	-0.35	12	15
Syndecan-1/RANTES	-0.11	0.1	0.27	3	-0.37	18	21
Syndecan-1/CD147	-0.1	0.1	0.36	1	-0.4	9	10
Syndecan-1/Syntenin/PIP2	-0.095	0.094	0.26	2	-0.36	12	14
LAMA5	0.017	0.042	0.36	3	-0.41	2	5
positive regulation of cell-cell adhesion	-0.093	0.092	0.26	2	-0.35	12	14
MMP7	-0.41	0.11	0.36	3	-0.43	429	432
HGF	0.017	0.06	-10000	0	-0.4	9	9
Syndecan-1/CASK	-0.11	0.093	0.28	2	-0.29	32	34
Syndecan-1/HGF/MET	-0.1	0.1	0.24	1	-0.39	14	15
regulation of cell adhesion	-0.099	0.088	0.32	1	-0.38	8	9
HPSE	0.023	0.04	-10000	0	-0.4	4	4
positive regulation of cell migration	-0.11	0.099	0.3	3	-0.29	31	34
SDC1	-0.11	0.099	0.3	3	-0.3	31	34
Syndecan-1/Collagen	-0.11	0.099	0.3	3	-0.29	31	34
PPIB	0.026	0.006	-10000	0	-10000	0	0
MET	0.023	0.046	0.36	1	-0.43	4	5
PRKACA	0.027	0.003	-10000	0	-10000	0	0
MMP9	-0.002	0.12	0.36	11	-0.42	27	38
MAPK1	-0.099	0.091	0.34	1	-0.38	9	10
homophilic cell adhesion	-0.11	0.1	0.3	3	-0.3	32	35
MMP1	-0.27	0.22	0.36	2	-0.43	290	292

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.01	0.063	-10000	0	-0.25	25	25
EPHB2	0.024	0.031	-10000	0	-0.43	2	2
Syndecan-2/TACI	-0.057	0.11	-10000	0	-0.23	134	134
LAMA1	-0.057	0.16	-10000	0	-0.4	84	84
Syndecan-2/alpha2 ITGB1	0.041	0.031	-10000	0	-0.22	1	1
HRAS	0.026	0.02	-10000	0	-0.4	1	1
Syndecan-2/CASK	0.008	0.003	-10000	0	-10000	0	0
ITGA5	0.024	0.037	-10000	0	-0.43	3	3
BAX	0.006	0.003	-10000	0	-10000	0	0
EPB41	0.026	0.007	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.022	0.015	-10000	0	-0.2	1	1
LAMA3	0.019	0.036	-10000	0	-0.41	3	3
EZR	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.021	0.051	-10000	0	-0.42	6	6
Syndecan-2/MMP2	0.022	0.03	-10000	0	-0.24	5	5
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.04	0.007	-10000	0	-10000	0	0
dendrite morphogenesis	0.022	0.022	-10000	0	-0.25	2	2
Syndecan-2/GM-CSF	-0.064	0.14	-10000	0	-0.25	151	151
determination of left/right symmetry	0.011	0.005	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.025	0.011	-10000	0	-10000	0	0
GNB2L1	0.027	0.003	-10000	0	-10000	0	0
MAPK3	-0.054	0.14	0.19	39	-0.23	149	188
MAPK1	-0.054	0.13	0.19	39	-0.23	149	188
Syndecan-2/RACK1	0.036	0.02	-10000	0	-0.2	1	1
NF1	0.026	0.005	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.011	0.005	-10000	0	-10000	0	0
ITGA2	0.027	0.004	-10000	0	-10000	0	0
MAPK8	0.01	0.004	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.002	0.089	-10000	0	-10000	0	0
Syndecan-2/Kininogen	-0.027	0.1	-10000	0	-0.23	88	88
ITGB1	0.027	0.002	-10000	0	-10000	0	0
SRC	0.018	0.04	0.18	22	-10000	0	22
Syndecan-2/CASK/Protein 4.1	0.022	0.011	-10000	0	-10000	0	0
extracellular matrix organization	0.024	0.017	-10000	0	-0.25	1	1
actin cytoskeleton reorganization	0.01	0.063	-10000	0	-0.25	25	25
Syndecan-2/Caveolin-2/Ras	0.034	0.033	-10000	0	-0.22	5	5
Syndecan-2/Laminin alpha3	0.02	0.019	-10000	0	-0.25	1	1
Syndecan-2/RasGAP	0.045	0.025	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.038	0.028	-10000	0	-0.3	3	3
PRKCD	0.027	0.004	-10000	0	-10000	0	0
Syndecan-2 dimer	0.022	0.022	-10000	0	-0.25	2	2
GO:0007205	0.002	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.021	0.023	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
SDCBP	0.023	0.022	-10000	0	-0.4	1	1
TNFRSF13B	-0.12	0.19	-10000	0	-0.4	152	152
RASA1	0.027	0.005	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.04	0.007	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0.025	0.011	-10000	0	-10000	0	0
TGFB1	0.026	0.022	-10000	0	-0.43	1	1
CASP3	0.037	0.06	0.19	57	-10000	0	57
FN1	0	0.11	-10000	0	-0.42	28	28
Syndecan-2/IL8	-0.11	0.15	-10000	0	-0.25	227	227
SDC2	0.011	0.005	-10000	0	-10000	0	0
KNG1	-0.078	0.17	-10000	0	-0.4	101	101
Syndecan-2/Neurofibromin	0.025	0.011	-10000	0	-10000	0	0
TRAPPC4	0.027	0.004	-10000	0	-10000	0	0
CSF2	-0.15	0.22	-10000	0	-0.43	173	173
Syndecan-2/TGFB1	0.024	0.017	-10000	0	-0.25	1	1
Syndecan-2/Syntenin/PI-4-5-P2	0.022	0.015	-10000	0	-0.21	1	1
Syndecan-2/Ezrin	0.038	0.017	-10000	0	-10000	0	0
PRKACA	0.038	0.06	0.19	58	-10000	0	58
angiogenesis	-0.11	0.15	-10000	0	-0.25	227	227
MMP2	0.021	0.05	-10000	0	-0.41	6	6
IL8	-0.24	0.23	0.36	1	-0.43	260	261
calcineurin-NFAT signaling pathway	-0.056	0.11	-10000	0	-0.23	134	134

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.03	0.16	0.22	2	-0.39	46	48
PTK2B	0.021	0.023	-10000	0	-0.4	1	1
mol:Ca2+	-0.017	0.25	-10000	0	-0.88	29	29
EDN1	0.016	0.12	-10000	0	-0.29	22	22
EDN3	-0.12	0.19	-10000	0	-0.4	146	146
EDN2	-0.094	0.19	-10000	0	-0.4	127	127
HRAS/GDP	0	0.15	0.23	9	-0.43	18	27
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.011	0.11	-10000	0	-0.39	14	14
ADCY4	-0.043	0.13	-10000	0	-0.39	35	35
ADCY5	-0.12	0.17	-10000	0	-0.4	88	88
ADCY6	-0.044	0.14	-10000	0	-0.39	36	36
ADCY7	-0.044	0.14	-10000	0	-0.39	36	36
ADCY1	-0.045	0.14	0.39	1	-0.4	35	36
ADCY2	-0.06	0.15	-10000	0	-0.41	48	48
ADCY3	-0.044	0.13	-10000	0	-0.38	36	36
ADCY8	-0.045	0.13	0.22	1	-0.39	28	29
ADCY9	-0.045	0.14	-10000	0	-0.39	36	36
arachidonic acid secretion	-0.024	0.16	0.25	4	-0.46	29	33
ETB receptor/Endothelin-1/Gq/GTP	0.006	0.077	-10000	0	-0.31	14	14
GNAO1	-0.088	0.19	-10000	0	-0.4	122	122
HRAS	0.026	0.02	-10000	0	-0.4	1	1
ETA receptor/Endothelin-1/G12/GTP	0.056	0.2	0.29	4	-0.39	33	37
ETA receptor/Endothelin-1/Gs/GTP	0.032	0.2	0.3	2	-0.4	37	39
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.034	0.18	-10000	0	-0.45	42	42
EDNRB	0.005	0.076	-10000	0	-0.39	14	14
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.041	0.19	0.25	1	-0.55	39	40
CYSLTR1	-0.073	0.24	0.23	1	-0.54	84	85
SLC9A1	-0.009	0.1	-10000	0	-0.26	43	43
mol:GDP	-0.011	0.15	0.23	9	-0.44	23	32
SLC9A3	-0.25	0.33	-10000	0	-0.64	123	123
RAF1	-0.014	0.13	0.27	3	-0.5	10	13
JUN	0.006	0.16	-10000	0	-0.62	11	11
JAK2	-0.032	0.17	0.23	1	-0.42	39	40
mol:IP3	0.022	0.11	0.21	8	-0.54	5	13
ETA receptor/Endothelin-1	0.042	0.25	0.34	4	-0.45	48	52
PLCB1	0.025	0.03	0.36	3	-10000	0	3
PLCB2	0.026	0.007	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.091	0.17	-10000	0	-0.31	150	150
FOS	-0.014	0.16	-10000	0	-0.87	9	9
Gai/GDP	-0.16	0.34	-10000	0	-0.68	128	128
CRK	0.023	0.011	-10000	0	-10000	0	0
mol:Ca ++	-0.007	0.16	0.23	7	-0.42	29	36
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
PRKCB1	0.019	0.1	0.2	8	-0.52	5	13
GNAQ	0.025	0.023	-10000	0	-0.4	1	1
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
GNAL	0.006	0.08	-10000	0	-0.4	17	17
Gs family/GDP	-0.015	0.14	0.29	1	-0.41	25	26
ETA receptor/Endothelin-1/Gq/GTP	0.006	0.12	0.24	1	-0.46	8	9
MAPK14	0.009	0.077	0.23	3	-0.47	4	7
TRPC6	-0.021	0.26	-10000	0	-0.94	29	29
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.011	0.078	-10000	0	-0.32	11	11
ETB receptor/Endothelin-2	-0.045	0.13	-10000	0	-0.28	101	101
ETB receptor/Endothelin-3	-0.079	0.14	-10000	0	-0.29	136	136
ETB receptor/Endothelin-1	0.016	0.11	-10000	0	-0.36	15	15
MAPK3	-0.011	0.14	0.3	1	-0.67	10	11
MAPK1	-0.018	0.16	-10000	0	-0.79	10	10
Rac1/GDP	-0.006	0.14	0.25	5	-0.42	20	25
cAMP biosynthetic process	-0.087	0.15	0.24	1	-0.41	47	48
MAPK8	0.002	0.2	-10000	0	-0.62	28	28
SRC	0.017	0.013	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.046	0.14	-10000	0	-0.33	62	62
p130Cas/CRK/Src/PYK2	-0.013	0.19	0.28	13	-0.55	27	40
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.006	0.14	0.26	4	-0.43	19	23
COL1A2	-0.001	0.18	0.34	1	-0.43	32	33
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.078	0.19	-10000	0	-0.32	143	143
mol:DAG	0.022	0.11	0.21	8	-0.54	5	13
MAP2K2	-0.015	0.13	0.26	3	-0.54	12	15
MAP2K1	-0.014	0.13	0.26	3	-0.54	12	15
EDNRA	-0.009	0.16	-10000	0	-0.38	46	46
positive regulation of muscle contraction	-0.009	0.15	0.25	28	-0.38	32	60
Gq family/GDP	0	0.13	-10000	0	-0.5	9	9
HRAS/GTP	-0.015	0.13	0.24	3	-0.4	19	22
PRKCH	0.017	0.1	0.2	5	-0.58	4	9
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.021	0.11	0.25	6	-0.69	3	9
PRKCB	-0.017	0.15	0.2	9	-0.39	35	44
PRKCE	0.018	0.1	0.2	7	-0.68	3	10
PRKCD	0.017	0.11	0.2	7	-0.68	3	10
PRKCG	-0.046	0.15	0.22	8	-0.43	20	28
regulation of vascular smooth muscle contraction	-0.018	0.18	-10000	0	-1	9	9
PRKCQ	0.017	0.11	0.2	7	-0.5	6	13
PLA2G4A	-0.027	0.17	0.25	4	-0.5	29	33
GNA14	0.024	0.031	-10000	0	-0.4	2	2
GNA15	0.021	0.049	-10000	0	-0.42	5	5
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA11	0.024	0.03	-10000	0	-0.4	2	2
Rac1/GTP	0.056	0.2	0.29	4	-0.39	33	37
MMP1	-0.19	0.18	0.29	2	-0.33	230	232

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.034	0.051	-10000	0	-0.21	18	18
RGS9BP	0.021	0.031	0.36	1	-0.43	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.011	0.031	-10000	0	-0.43	2	2
mol:Na +	-0.051	0.13	0.23	5	-0.24	130	135
mol:ADP	-0.013	0.034	-10000	0	-0.39	3	3
GNAT2	0.015	0.057	-10000	0	-0.43	7	7
RGS9-1/Gbeta5/R9AP	0.007	0.1	0.25	1	-0.24	67	68
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.023	0.039	-10000	0	-0.26	8	8
GRK7	0.009	0.036	-10000	0	-0.43	2	2
CNGB3	-0.013	0.093	0.36	7	-0.43	16	23
Cone Metarhodopsin II/X-Arrestin	0.013	0.021	-10000	0	-0.3	2	2
mol:Ca2+	-0.068	0.14	0.18	40	-0.24	148	188
Cone PDE6	0.021	0.099	0.25	1	-0.23	2	3
Cone Metarhodopsin II	0.019	0.03	-10000	0	-0.3	3	3
Na + (4 Units)	-0.057	0.14	0.23	6	-0.24	151	157
GNAT2/GDP	0.014	0.097	0.24	1	-0.2	64	65
GNB5	0.026	0.006	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.017	0.033	0.18	2	-0.24	8	10
Cone Transducin	0.037	0.055	-10000	0	-0.22	18	18
SLC24A2	-0.029	0.13	0.36	3	-0.43	40	43
GNB3/GNGT2	0.031	0.051	-10000	0	-0.29	11	11
GNB3	0.023	0.042	-10000	0	-0.42	4	4
GNAT2/GTP	0.014	0.04	-10000	0	-0.3	7	7
CNGA3	-0.11	0.19	-10000	0	-0.4	137	137
ARR3	-0.008	0.034	-10000	0	-0.43	2	2
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.051	0.13	0.23	5	-0.24	130	135
mol:Pi	0.007	0.1	0.25	1	-0.23	67	68
Cone CNG Channel	-0.035	0.12	-10000	0	-0.26	20	20
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	-0.029	0.13	0.36	3	-0.43	40	43
RGS9	-0.037	0.15	-10000	0	-0.4	67	67
PDE6C	-0.005	0.02	-10000	0	-10000	0	0
GNGT2	0.02	0.053	-10000	0	-0.4	7	7
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.015	0.023	-10000	0	-0.43	1	1

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.004	0.11	-10000	0	-0.23	71	71
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.095	0.33	1	-0.36	3	4
AP1	-0.038	0.093	-10000	0	-0.33	10	10
mol:PIP3	-0.027	0.081	-10000	0	-0.33	8	8
AKT1	0.002	0.083	0.24	2	-0.32	8	10
PTK2B	-0.053	0.11	0.22	1	-0.33	34	35
RHOA	0.006	0.067	0.22	3	-0.36	9	12
PIK3CB	0.027	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.003	0.055	-10000	0	-0.26	1	1
MAGI3	0.025	0.021	-10000	0	-0.39	1	1
RELA	0.027	0.004	-10000	0	-10000	0	0
apoptosis	-0.035	0.11	-10000	0	-0.24	88	88
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
positive regulation of microtubule depolymerization	-0.083	0.13	0.21	4	-0.35	53	57
NF kappa B1 p50/RelA	-0.039	0.09	-10000	0	-0.39	7	7
endothelial cell migration	-0.019	0.099	-10000	0	-0.25	66	66
ADCY4	-0.08	0.18	-10000	0	-0.44	75	75
ADCY5	-0.16	0.24	-10000	0	-0.5	122	122
ADCY6	-0.077	0.18	-10000	0	-0.45	69	69
ADCY7	-0.075	0.18	-10000	0	-0.46	67	67
ADCY1	-0.077	0.17	-10000	0	-0.45	68	68
ADCY2	-0.094	0.2	-10000	0	-0.48	82	82
ADCY3	-0.076	0.18	-10000	0	-0.45	69	69
ADCY8	-0.075	0.17	-10000	0	-0.44	68	68
ADCY9	-0.077	0.18	-10000	0	-0.45	70	70
GSK3B	-0.051	0.11	0.2	1	-0.34	28	29
arachidonic acid secretion	-0.092	0.19	-10000	0	-0.45	79	79
GNG2	0.01	0.08	-10000	0	-0.39	17	17
TRIP6	0.013	0.021	-10000	0	-0.32	1	1
GNAO1	-0.079	0.16	-10000	0	-0.29	143	143
HRAS	0.026	0.02	-10000	0	-0.4	1	1
NFKBIA	-0.027	0.093	0.34	1	-0.33	12	13
GAB1	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.078	0.31	-10000	0	-0.85	62	62
JUN	0.026	0.005	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.035	0.023	-10000	0	-0.24	2	2
TIAM1	-0.11	0.36	-10000	0	-1	62	62
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.013	0.05	-10000	0	-0.27	1	1
PLCB3	0.015	0.021	0.18	2	-0.23	1	3
FOS	0.022	0.035	-10000	0	-0.4	3	3
positive regulation of mitosis	-0.092	0.19	-10000	0	-0.45	79	79
LPA/LPA1-2-3	-0.008	0.12	-10000	0	-0.22	93	93
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	-0.001	0.001	-10000	0	-10000	0	0
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
stress fiber formation	-0.032	0.099	0.23	1	-0.3	26	27
GNAZ	-0.019	0.092	-10000	0	-0.24	67	67
EGFR/PI3K-beta/Gab1	-0.017	0.089	-10000	0	-0.34	8	8
positive regulation of dendritic cell cytokine production	-0.009	0.11	-10000	0	-0.22	93	93
LPA/LPA2/MAGI-3	0.035	0.023	-10000	0	-0.24	2	2
ARHGEF1	0.006	0.097	0.2	44	-0.37	2	46
GNAI2	-0.015	0.087	-10000	0	-0.23	59	59
GNAI3	-0.017	0.089	-10000	0	-0.23	66	66
GNAI1	-0.022	0.1	-10000	0	-0.26	67	67
LPA/LPA3	-0.005	0.08	-10000	0	-0.28	35	35
LPA/LPA2	0.02	0.019	-10000	0	-0.3	1	1
LPA/LPA1	-0.019	0.11	-10000	0	-0.27	67	67
HB-EGF/EGFR	0.003	0.073	0.21	10	-0.26	27	37
HBEGF	-0.006	0.088	0.27	11	-0.3	29	40
mol:DAG	-0.013	0.05	-10000	0	-0.27	1	1
cAMP biosynthetic process	-0.1	0.19	0.32	1	-0.42	90	91
NFKB1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.017	0.013	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
LYN	-0.009	0.095	0.3	2	-0.37	6	8
GNAQ	-0.003	0.063	-10000	0	-0.21	37	37
LPAR2	0.026	0.022	-10000	0	-0.42	1	1
LPAR3	-0.015	0.11	-10000	0	-0.4	35	35
LPAR1	-0.031	0.15	-10000	0	-0.39	63	63
IL8	-0.091	0.14	0.32	2	-0.4	12	14
PTK2	-0.027	0.089	0.19	2	-0.3	13	15
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
CASP3	-0.035	0.11	-10000	0	-0.24	88	88
EGFR	0.023	0.021	-10000	0	-0.4	1	1
PLCG1	-0.01	0.059	-10000	0	-0.22	30	30
PLD2	-0.033	0.094	0.19	2	-0.32	11	13
G12/G13	0.015	0.091	-10000	0	-0.21	56	56
PI3K-beta	-0.011	0.081	-10000	0	-0.35	9	9
cell migration	-0.017	0.11	-10000	0	-0.25	58	58
SLC9A3R2	0.026	0.02	-10000	0	-0.4	1	1
PXN	-0.033	0.1	0.23	1	-0.3	26	27
HRAS/GTP	-0.094	0.2	-10000	0	-0.46	79	79
RAC1	0.025	0.008	-10000	0	-10000	0	0
MMP9	-0.003	0.12	0.36	11	-0.43	27	38
PRKCE	0.027	0.003	-10000	0	-10000	0	0
PRKCD	-0.005	0.058	0.31	2	-10000	0	2
Gi(beta/gamma)	-0.084	0.19	0.16	2	-0.42	84	86
mol:LPA	0.001	0.014	-10000	0	-0.15	1	1
TRIP6/p130 Cas/FAK1/Paxillin	0.002	0.11	-10000	0	-0.38	9	9
MAPKKK cascade	-0.092	0.19	-10000	0	-0.45	79	79
contractile ring contraction involved in cytokinesis	0.007	0.067	0.22	3	-0.35	9	12
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.004	0.065	-10000	0	-0.22	32	32
GNA15	-0.004	0.064	-10000	0	-0.2	41	41
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.086	0.13	0.22	3	-0.36	53	56
GNA11	-0.003	0.063	-10000	0	-0.21	38	38
Rac1/GTP	-0.084	0.33	-10000	0	-0.9	62	62
MMP2	-0.019	0.099	-10000	0	-0.25	66	66

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.026	0.11	-10000	0	-0.38	17	17
MAP4K1	-0.016	0.13	-10000	0	-0.4	46	46
MAP3K8	0.027	0.002	-10000	0	-10000	0	0
PRKCB	-0.068	0.18	-10000	0	-0.4	101	101
DBNL	0.025	0.008	-10000	0	-10000	0	0
CRKL	0.026	0.006	-10000	0	-10000	0	0
MAP3K1	-0.011	0.1	-10000	0	-0.34	31	31
JUN	-0.13	0.28	-10000	0	-0.6	112	112
MAP3K7	-0.011	0.1	-10000	0	-0.34	30	30
GRAP2	0.012	0.073	-10000	0	-0.4	14	14
CRK	0.023	0.01	-10000	0	-10000	0	0
MAP2K4	-0.019	0.12	0.23	1	-0.37	33	34
LAT	0.024	0.035	-10000	0	-0.41	3	3
LCP2	0.023	0.04	-10000	0	-0.4	4	4
MAPK8	-0.13	0.3	-10000	0	-0.63	112	112
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.007	0.11	-10000	0	-0.35	32	32
LAT/GRAP2/SLP76/HPK1/HIP-55	0.032	0.11	-10000	0	-0.39	11	11

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.014	0.1	-10000	0	-0.31	31	31
alphaM/beta2 Integrin/GPIbA	0.007	0.095	-10000	0	-0.29	32	32
alphaM/beta2 Integrin/proMMP-9	-0.001	0.1	0.25	11	-0.28	42	53
PLAUR	0.027	0.003	-10000	0	-10000	0	0
HMGB1	0.014	0.023	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.017	0.094	-10000	0	-0.3	27	27
AGER	0.017	0.035	-10000	0	-0.47	1	1
RAP1A	0.026	0.005	-10000	0	-10000	0	0
SELPLG	0.024	0.035	-10000	0	-0.4	3	3
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.014	0.1	-10000	0	-0.41	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.002	0.12	0.36	11	-0.42	27	38
CYR61	0.022	0.043	-10000	0	-0.43	4	4
TLN1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP	-0.028	0.1	-10000	0	-0.32	20	20
RHOA	0.027	0.004	-10000	0	-10000	0	0
P-selectin oligomer	-0.03	0.14	-10000	0	-0.4	60	60
MYH2	-0.045	0.1	-10000	0	-0.31	25	25
MST1R	0.027	0.004	-10000	0	-10000	0	0
leukocyte activation during inflammatory response	-0.022	0.12	-10000	0	-0.24	92	92
APOB	-0.049	0.15	-10000	0	-0.4	67	67
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.021	0.05	-10000	0	-0.41	6	6
JAM3	0.027	0.004	-10000	0	-10000	0	0
GP1BA	0.014	0.046	-10000	0	-0.4	5	5
alphaM/beta2 Integrin/CTGF	0.014	0.098	-10000	0	-0.3	31	31
alphaM/beta2 Integrin	-0.044	0.11	-10000	0	-0.29	44	44
JAM3 homodimer	0.027	0.004	-10000	0	-10000	0	0
ICAM2	0.027	0.005	-10000	0	-10000	0	0
ICAM1	0.026	0.022	-10000	0	-0.43	1	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.043	0.11	-10000	0	-0.28	44	44
cell adhesion	0.007	0.095	-10000	0	-0.29	32	32
NFKB1	0.013	0.14	0.32	2	-0.42	13	15
THY1	0.009	0.089	-10000	0	-0.43	18	18
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	-0.018	0.11	-10000	0	-0.25	79	79
alphaM/beta2 Integrin/LRP/tPA	0.034	0.085	-10000	0	-0.32	12	12
IL6	-0.02	0.16	-10000	0	-0.35	66	66
ITGB2	0.009	0.063	-10000	0	-0.4	9	9
elevation of cytosolic calcium ion concentration	0.014	0.12	-10000	0	-0.26	63	63
alphaM/beta2 Integrin/JAM2/JAM3	-0.017	0.15	-10000	0	-0.4	32	32
JAM2	-0.066	0.17	-10000	0	-0.4	98	98
alphaM/beta2 Integrin/ICAM1	0.005	0.13	-10000	0	-0.32	26	26
alphaM/beta2 Integrin/uPA/Plg	-0.045	0.15	-10000	0	-0.26	139	139
RhoA/GTP	-0.047	0.11	-10000	0	-0.31	32	32
positive regulation of phagocytosis	-0.028	0.1	0.18	3	-0.42	14	17
Ron/MSP	-0.013	0.12	-10000	0	-0.3	69	69
alphaM/beta2 Integrin/uPAR/uPA	0.016	0.12	-10000	0	-0.26	63	63
alphaM/beta2 Integrin/uPAR	0.017	0.094	-10000	0	-0.3	27	27
PLAU	-0.009	0.12	-10000	0	-0.43	36	36
PLAT	0.022	0.029	-10000	0	-0.4	2	2
actin filament polymerization	-0.045	0.1	0.24	2	-0.3	23	25
MST1	-0.043	0.16	-10000	0	-0.43	69	69
alphaM/beta2 Integrin/lipoprotein(a)	-0.018	0.13	-10000	0	-0.24	92	92
TNF	0.008	0.14	-10000	0	-0.49	9	9
RAP1B	0.027	0.002	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.005	0.12	-10000	0	-0.29	63	63
fibrinolysis	-0.046	0.15	-10000	0	-0.26	139	139
HCK	0.01	0.053	-10000	0	-0.4	7	7
dendritic cell antigen processing and presentation	-0.043	0.11	-10000	0	-0.28	44	44
VTN	0.006	0.079	-10000	0	-0.43	14	14
alphaM/beta2 Integrin/CYR61	0.015	0.097	-10000	0	-0.3	31	31
LPA	-0.008	0.081	-10000	0	-0.44	14	14
LRP1	0.025	0.028	-10000	0	-0.4	2	2
cell migration	-0.006	0.1	0.21	10	-0.28	42	52
FN1	0	0.11	-10000	0	-0.42	28	28
alphaM/beta2 Integrin/Thy1	0.006	0.11	-10000	0	-0.29	45	45
MPO	0.003	0.096	-10000	0	-0.43	21	21
KNG1	-0.078	0.17	-10000	0	-0.4	101	101
RAP1/GDP	0.036	0.008	-10000	0	-10000	0	0
ROCK1	-0.043	0.1	0.2	1	-0.3	26	27
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.083	0.17	-10000	0	-0.43	83	83
CTGF	0.023	0.043	-10000	0	-0.43	4	4
alphaM/beta2 Integrin/Hck	0.007	0.081	-10000	0	-0.3	21	21
ITGAM	-0.007	0.1	-10000	0	-0.4	26	26
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.005	0.14	-10000	0	-0.28	68	68
HP	-0.006	0.1	-10000	0	-0.43	25	25
leukocyte adhesion	-0.036	0.14	-10000	0	-0.42	27	27
SELP	-0.03	0.14	-10000	0	-0.4	60	60

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.004	0.16	0.28	6	-0.5	34	40
FYN	-0.032	0.2	0.26	2	-0.58	42	44
LAT/GRAP2/SLP76	-0.011	0.17	0.2	1	-0.52	37	38
IKBKB	0.024	0.009	-10000	0	-10000	0	0
AKT1	-0.025	0.14	0.17	2	-0.41	44	46
B2M	0.024	0.022	-10000	0	-0.4	1	1
IKBKG	-0.002	0.049	0.09	23	-0.14	21	44
MAP3K8	0.027	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.035	0.088	5	-0.11	51	56
integrin-mediated signaling pathway	0.032	0.029	-10000	0	-0.23	5	5
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.04	0.2	0.2	1	-0.61	42	43
TRPV6	-0.018	0.25	1.1	14	-0.42	51	65
CD28	0.01	0.084	-10000	0	-0.4	18	18
SHC1	-0.033	0.19	0.3	6	-0.56	42	48
receptor internalization	-0.04	0.22	-10000	0	-0.63	43	43
PRF1	-0.037	0.24	-10000	0	-0.77	33	33
KRAS	0.027	0.003	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
COT/AKT1	-0.009	0.12	0.16	2	-0.33	41	43
LAT	-0.036	0.19	0.2	2	-0.57	42	44
EntrezGene:6955	0	0.002	-10000	0	-10000	0	0
CD3D	0.015	0.073	-10000	0	-0.4	13	13
CD3E	0.012	0.08	-10000	0	-0.4	16	16
CD3G	-0.007	0.12	-10000	0	-0.4	36	36
RASGRP2	-0.01	0.054	-10000	0	-0.17	42	42
RASGRP1	-0.005	0.15	0.21	5	-0.43	38	43
HLA-A	0	0.003	-10000	0	-10000	0	0
RASSF5	0.022	0.045	-10000	0	-0.4	5	5
RAP1A/GTP/RAPL	0.032	0.029	-10000	0	-0.23	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.059	0.12	20	-0.13	27	47
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.02	0.069	-10000	0	-0.22	35	35
PRKCA	0.019	0.098	0.16	30	-0.26	26	56
GRAP2	0.012	0.073	-10000	0	-0.4	14	14
mol:IP3	-0.008	0.14	0.2	45	-0.41	31	76
EntrezGene:6957	0	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.033	0.18	-10000	0	-0.57	39	39
ORAI1	-0.001	0.19	0.36	5	-0.95	14	19
CSK	-0.032	0.19	0.19	1	-0.56	43	44
B7 family/CD28	-0.008	0.21	-10000	0	-0.61	39	39
CHUK	0.026	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.041	0.22	0.19	1	-0.65	43	44
PTPN6	-0.036	0.19	0.2	5	-0.56	43	48
VAV1	-0.042	0.2	0.22	2	-0.58	45	47
Monovalent TCR/CD3	-0.02	0.15	-10000	0	-0.41	45	45
CBL	0.027	0.004	-10000	0	-10000	0	0
LCK	-0.037	0.2	0.28	1	-0.56	46	47
PAG1	-0.022	0.2	0.2	31	-0.55	43	74
RAP1A	0.026	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.039	0.22	0.19	1	-0.63	44	45
CD80	0.024	0.036	-10000	0	-0.41	3	3
CD86	0.018	0.063	-10000	0	-0.4	10	10
PDK1/CARD11/BCL10/MALT1	-0.016	0.087	-10000	0	-0.26	35	35
HRAS	0.026	0.02	-10000	0	-0.4	1	1
GO:0035030	-0.031	0.16	-10000	0	-0.49	41	41
CD8A	-0.003	0.11	-10000	0	-0.4	33	33
CD8B	0.014	0.075	-10000	0	-0.4	14	14
PTPRC	-0.007	0.12	-10000	0	-0.4	36	36
PDK1/PKC theta	-0.023	0.17	0.21	4	-0.5	40	44
CSK/PAG1	-0.019	0.19	0.22	6	-0.58	36	42
SOS1	0.027	0.002	-10000	0	-10000	0	0
peptide-MHC class I	0.017	0.018	-10000	0	-0.28	1	1
GRAP2/SLP76	-0.014	0.2	-10000	0	-0.59	40	40
STIM1	0.015	0.12	1.2	4	-10000	0	4
RAS family/GTP	0.021	0.069	0.15	14	-0.18	17	31
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.045	0.24	-10000	0	-0.68	43	43
mol:DAG	-0.023	0.11	-10000	0	-0.35	34	34
RAP1A/GDP	0.011	0.028	0.065	14	-0.065	7	21
PLCG1	0.016	0.013	-10000	0	-10000	0	0
CD247	0.015	0.072	-10000	0	-0.4	13	13
cytotoxic T cell degranulation	-0.034	0.22	-10000	0	-0.73	33	33
RAP1A/GTP	-0.004	0.02	-10000	0	-0.065	41	41
mol:PI-3-4-5-P3	-0.029	0.17	0.19	2	-0.49	42	44
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.011	0.17	0.22	41	-0.52	32	73
NRAS	0.025	0.029	-10000	0	-0.4	2	2
ZAP70	0.015	0.072	-10000	0	-0.4	13	13
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.021	0.17	0.21	1	-0.51	38	39
MALT1	0.02	0.023	-10000	0	-0.4	1	1
TRAF6	0.027	0.004	-10000	0	-10000	0	0
CD8 heterodimer	0.009	0.11	-10000	0	-0.34	39	39
CARD11	0.002	0.1	0.36	2	-0.41	25	27
PRKCB	-0.004	0.12	0.16	26	-0.3	48	74
PRKCE	0.02	0.1	0.16	31	-0.26	28	59
PRKCQ	-0.027	0.19	0.2	3	-0.57	40	43
LCP2	0.023	0.04	-10000	0	-0.4	4	4
BCL10	0.026	0.021	-10000	0	-0.4	1	1
regulation of survival gene product expression	-0.019	0.12	0.16	3	-0.35	43	46
IKK complex	0.021	0.065	0.11	107	-0.12	24	131
RAS family/GDP	-0.002	0.012	-10000	0	-0.062	1	1
MAP3K14	-0.008	0.091	0.13	3	-0.26	37	40
PDPK1	-0.022	0.13	0.17	4	-0.4	39	43
TCR/CD3/MHC I/CD8/Fyn	-0.045	0.23	-10000	0	-0.66	43	43

×

IGF1 pathway

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
NCK2	0.027	0	-10000	0	-10000	0	0
PTK2	0.023	0.01	-10000	0	-10000	0	0
CRKL	-0.035	0.092	-10000	0	-0.2	102	102
GRB2/SOS1/SHC	0.053	0.013	-10000	0	-10000	0	0
HRAS	0.026	0.02	-10000	0	-0.4	1	1
IRS1/Crk	-0.031	0.097	-10000	0	-0.2	104	104
IGF-1R heterotetramer/IGF1/PTP1B	-0.011	0.093	-10000	0	-0.22	67	67
AKT1	-0.05	0.074	0.17	1	-10000	0	1
BAD	-0.05	0.071	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.027	0.084	-10000	0	-0.2	82	82
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.027	0.1	-10000	0	-0.2	111	111
RAF1	-0.033	0.088	-10000	0	-0.45	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.001	0.11	-10000	0	-10000	0	0
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.029	0.11	-10000	0	-0.22	112	112
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
RPS6KB1	-0.05	0.074	0.17	1	-10000	0	1
GNB2L1	0.027	0.003	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.015	0.082	0.26	2	-0.38	2	4
PXN	0.027	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-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	-0.018	0.091	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.015	0.11	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.006	0.04	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.014	0.11	-10000	0	-0.2	112	112
Crk/p130 Cas/Paxillin	0	0.11	-10000	0	-10000	0	0
IGF1R	0.006	0.041	-10000	0	-10000	0	0
IGF1	-0.081	0.19	-10000	0	-0.41	112	112
IRS2/Crk	-0.022	0.082	-10000	0	-10000	0	0
PI3K	-0.002	0.11	-10000	0	-10000	0	0
apoptosis	0.038	0.062	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
PRKCD	-0.063	0.14	-10000	0	-0.31	104	104
RAF1/14-3-3 E	-0.018	0.083	-10000	0	-0.38	6	6
BAD/14-3-3	-0.04	0.065	-10000	0	-10000	0	0
PRKCZ	-0.05	0.074	0.17	1	-10000	0	1
Crk/p130 Cas/Paxillin/FAK1	-0.013	0.08	-10000	0	-10000	0	0
PTPN1	0.016	0.014	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.062	0.15	-10000	0	-0.32	112	112
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0	0.11	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.027	0.002	-10000	0	-10000	0	0
IRS1/NCK2	-0.027	0.1	-10000	0	-0.2	112	112
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	-0.039	0.095	-10000	0	-0.2	111	111
IRS1	-0.043	0.1	-10000	0	-0.22	112	112
IRS2	-0.029	0.084	-10000	0	-0.2	83	83
IGF-1R heterotetramer/IGF1	-0.045	0.14	-10000	0	-0.3	112	112
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDPK1	-0.037	0.087	0.17	1	-10000	0	1
YWHAE	0.023	0.01	-10000	0	-10000	0	0
PRKD1	-0.064	0.14	0.2	1	-0.31	104	105
SHC1	0.027	0.004	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.007	0.072	0.27	3	-0.3	23	26
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.034	0.033	-10000	0	-0.3	4	4
STXBP1	0.022	0.048	-10000	0	-0.43	5	5
ACh/CHRNA1	-0.041	0.095	-10000	0	-0.22	65	65
RAB3GAP2/RIMS1/UNC13B	0.046	0.035	-10000	0	-0.25	5	5
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	0.006	0.051	-10000	0	-0.43	5	5
mol:ACh	-0.036	0.066	0.078	35	-0.12	147	182
RAB3GAP2	0.026	0.02	-10000	0	-0.4	1	1
STX1A/SNAP25/VAMP2	-0.034	0.11	-10000	0	-0.25	25	25
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.04	0.095	-10000	0	-0.22	65	65
UNC13B	0.027	0.004	-10000	0	-10000	0	0
CHRNA1	-0.012	0.12	-10000	0	-0.4	41	41
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.051	0.11	-10000	0	-0.25	80	80
SNAP25	-0.069	0.11	0.19	1	-0.25	130	131
VAMP2	0.004	0.002	-10000	0	-10000	0	0
SYT1	-0.031	0.14	-10000	0	-0.4	61	61
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.009	0.067	0.2	3	-0.25	26	29
STX1A/SNAP25 fragment 1/VAMP2	-0.034	0.11	-10000	0	-0.25	25	25

×

IL23-mediated signaling events

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
CCL2	-0.24	0.34	-10000	0	-1	45	45
IL23A	-0.28	0.35	-10000	0	-1	44	44
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.34	-10000	0	-0.99	42	42
positive regulation of T cell mediated cytotoxicity	-0.25	0.36	-10000	0	-1	43	43
ITGA3	-0.24	0.33	-10000	0	-1	36	36
IL17F	-0.21	0.25	-10000	0	-0.66	55	55
IL12B	-0.017	0.056	-10000	0	-0.44	4	4
STAT1 (dimer)	-0.24	0.35	-10000	0	-1	43	43
CD4	-0.25	0.36	-10000	0	-1.1	48	48
IL23	-0.27	0.34	-10000	0	-1	43	43
IL23R	-0.08	0.26	-10000	0	-1.1	25	25
IL1B	-0.27	0.35	-10000	0	-1	44	44
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.28	0.33	-10000	0	-0.99	40	40
TYK2	-0.005	0.032	-10000	0	-10000	0	0
STAT4	0.006	0.093	-10000	0	-0.4	23	23
STAT3	0.026	0.006	-10000	0	-10000	0	0
IL18RAP	0.003	0.095	-10000	0	-0.4	24	24
IL12RB1	-0.021	0.086	-10000	0	-0.42	17	17
PIK3CA	0.027	0.005	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.013	0.072	-10000	0	-0.31	17	17
IL23R/JAK2	-0.084	0.25	-10000	0	-1	24	24
positive regulation of chronic inflammatory response	-0.25	0.36	-10000	0	-1	43	43
natural killer cell activation	0.005	0.013	0.079	11	-10000	0	11
JAK2	-0.011	0.05	-10000	0	-0.42	3	3
PIK3R1	0.026	0.007	-10000	0	-10000	0	0
NFKB1	0.024	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	0.32	-10000	0	-0.94	44	44
ALOX12B	-0.24	0.33	-10000	0	-0.97	46	46
CXCL1	-0.28	0.34	-10000	0	-0.97	45	45
T cell proliferation	-0.25	0.36	-10000	0	-1	43	43
NFKBIA	0.023	0.007	-10000	0	-10000	0	0
IL17A	-0.19	0.22	-10000	0	-0.55	58	58
PI3K	-0.24	0.34	-10000	0	-0.96	48	48
IFNG	-0.01	0.037	0.14	11	-0.11	6	17
STAT3 (dimer)	-0.24	0.34	-10000	0	-0.96	45	45
IL18R1	0.017	0.06	-10000	0	-0.39	9	9
IL23/IL23R/JAK2/TYK2/SOCS3	-0.15	0.23	-10000	0	-0.73	32	32
IL18/IL18R	0.029	0.081	-10000	0	-0.23	35	35
macrophage activation	-0.018	0.016	-10000	0	-0.043	35	35
TNF	-0.26	0.34	-10000	0	-1	41	41
STAT3/STAT4	-0.24	0.35	-10000	0	-0.99	45	45
STAT4 (dimer)	-0.25	0.36	-10000	0	-1	48	48
IL18	0.023	0.03	-10000	0	-0.4	2	2
IL19	-0.23	0.32	-10000	0	-0.95	40	40
STAT5A (dimer)	-0.24	0.35	-10000	0	-1	41	41
STAT1	0.026	0.021	-10000	0	-0.43	1	1
SOCS3	0.026	0.022	-10000	0	-0.43	1	1
CXCL9	-0.26	0.34	-10000	0	-1	42	42
MPO	-0.23	0.32	-10000	0	-0.93	43	43
positive regulation of humoral immune response	-0.25	0.36	-10000	0	-1	43	43
IL23/IL23R/JAK2/TYK2	-0.26	0.37	-10000	0	-1.1	43	43
IL6	-0.25	0.36	-10000	0	-0.98	54	54
STAT5A	0.027	0.004	-10000	0	-10000	0	0
IL2	0.015	0.021	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.005	0.013	0.079	11	-10000	0	11
CD3E	-0.26	0.37	-10000	0	-1.1	50	50
keratinocyte proliferation	-0.25	0.36	-10000	0	-1	43	43
NOS2	-0.26	0.38	-10000	0	-1.1	52	52

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.086	0.13	-10000	0	-0.27	31	31
NF kappa B1 p50/RelA/I kappa B alpha	-0.071	0.12	0.32	4	-0.32	3	7
alphaV/beta3 Integrin/Osteopontin/Src	-0.12	0.17	-10000	0	-0.3	215	215
AP1	-0.068	0.14	-10000	0	-0.46	4	4
ILK	-0.096	0.13	-10000	0	-0.27	30	30
bone resorption	-0.079	0.12	0.33	2	-0.41	2	4
PTK2B	0.02	0.023	-10000	0	-0.4	1	1
PYK2/p130Cas	-0.068	0.14	-10000	0	-0.4	3	3
ITGAV	0.029	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.039	0.022	-10000	0	-0.28	2	2
alphaV/beta3 Integrin/Osteopontin	-0.093	0.16	-10000	0	-0.25	220	220
MAP3K1	-0.099	0.13	-10000	0	-0.27	33	33
JUN	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.099	0.12	-10000	0	-0.3	32	32
MAPK1	-0.099	0.12	-10000	0	-0.3	30	30
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.097	0.12	0.2	6	-0.31	5	11
ITGB3	0.024	0.044	-10000	0	-0.39	5	5
NFKBIA	-0.088	0.11	-10000	0	-0.29	32	32
FOS	0.023	0.035	-10000	0	-0.4	3	3
CD44	0.027	0.004	-10000	0	-10000	0	0
CHUK	0.026	0.006	-10000	0	-10000	0	0
PLAU	-0.086	0.13	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.07	0.14	-10000	0	-0.35	1	1
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
RELA	0.027	0.004	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.039	0.035	-10000	0	-0.28	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.097	0.13	-10000	0	-0.27	32	32
VAV3	-0.11	0.14	0.19	6	-0.39	37	43
MAP3K14	-0.1	0.13	-10000	0	-0.29	32	32
ROCK2	0.026	0.028	-10000	0	-0.4	2	2
SPP1	-0.19	0.23	-10000	0	-0.42	215	215
RAC1	0.025	0.008	-10000	0	-10000	0	0
Rac1/GTP	-0.094	0.13	-10000	0	-0.36	35	35
MMP2	-0.076	0.11	-10000	0	-0.52	5	5

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.025	0.094	-10000	0	-0.23	41	41
ER alpha/Gai/GDP/Gbeta gamma	-0.12	0.27	-10000	0	-0.63	73	73
AKT1	-0.058	0.28	-10000	0	-0.84	49	49
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.057	0.28	-10000	0	-0.85	49	49
mol:Ca2+	0.024	0.063	-10000	0	-0.4	2	2
IGF1R	0.026	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.013	0.075	-10000	0	-0.23	38	38
SHC1	0.027	0.004	-10000	0	-10000	0	0
apoptosis	0.054	0.26	0.79	49	-10000	0	49
RhoA/GTP	0.006	0.059	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.033	0.22	-10000	0	-0.54	52	52
regulation of stress fiber formation	0.019	0.054	0.29	2	-10000	0	2
E2/ERA-ERB (dimer)	0.008	0.08	-10000	0	-0.24	42	42
KRAS	0.027	0.003	-10000	0	-10000	0	0
G13/GTP	0.013	0.068	-10000	0	-0.21	38	38
pseudopodium formation	-0.019	0.054	-10000	0	-0.29	2	2
E2/ER alpha (dimer)/PELP1	0.009	0.073	-10000	0	-0.22	39	39
GRB2	0.027	0.004	-10000	0	-10000	0	0
GNG2	0.009	0.081	-10000	0	-0.4	17	17
GNAO1	-0.088	0.19	-10000	0	-0.4	122	122
HRAS	0.026	0.02	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.075	0.23	0.24	1	-0.62	57	58
E2/ER beta (dimer)	0.016	0.028	-10000	0	-0.28	4	4
mol:GDP	-0.016	0.1	-10000	0	-0.33	40	40
mol:NADP	-0.075	0.23	0.24	1	-0.62	57	58
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.006	0.039	-10000	0	-0.41	2	2
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
PLCB1	0.009	0.048	-10000	0	-0.44	3	3
PLCB2	0.008	0.054	-10000	0	-0.47	4	4
IGF1	-0.079	0.18	-10000	0	-0.4	112	112
mol:L-citrulline	-0.075	0.23	0.24	1	-0.62	57	58
RHOA	0.027	0.004	-10000	0	-10000	0	0
Gai/GDP	-0.17	0.34	-10000	0	-0.68	128	128
JNK cascade	0.016	0.028	-10000	0	-0.28	4	4
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
ESR2	0.021	0.041	-10000	0	-0.4	4	4
GNAQ	0.026	0.02	-10000	0	-0.4	1	1
ESR1	-0.012	0.12	-10000	0	-0.4	39	39
Gq family/GDP/Gbeta gamma	-0.003	0.14	-10000	0	-0.64	14	14
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.008	0.14	-10000	0	-0.6	12	12
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.03	0.22	-10000	0	-0.54	51	51
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
E2/ER alpha (dimer)	-0.006	0.083	-10000	0	-0.28	39	39
STRN	0.027	0.003	-10000	0	-10000	0	0
GNAL	0.006	0.08	-10000	0	-0.4	17	17
PELP1	0.023	0.01	-10000	0	-10000	0	0
MAPK11	0.009	0.03	-10000	0	-0.24	6	6
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
HBEGF	-0.007	0.26	0.3	104	-0.56	52	156
cAMP biosynthetic process	-0.002	0.077	-10000	0	-0.2	52	52
SRC	-0.054	0.26	-10000	0	-0.61	58	58
PI3K	0.039	0.008	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.007	0.11	-10000	0	-0.32	36	36
SOS1	0.027	0.002	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.092	0.18	-10000	0	-0.44	77	77
Gs family/GTP	0.003	0.08	-10000	0	-0.2	52	52
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.025	-10000	0	-0.21	3	3
vasodilation	-0.07	0.22	0.23	1	-0.59	57	58
mol:DAG	0.006	0.039	-10000	0	-0.41	2	2
Gs family/GDP/Gbeta gamma	-0.018	0.11	-10000	0	-0.32	38	38
MSN	-0.021	0.056	-10000	0	-0.32	2	2
Gq family/GTP	0.014	0.06	-10000	0	-0.49	4	4
mol:PI-3-4-5-P3	-0.053	0.27	-10000	0	-0.81	49	49
NRAS	0.025	0.029	-10000	0	-0.4	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.07	0.22	0.59	57	-0.23	1	58
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.1	-10000	0	-0.31	40	40
NOS3	-0.081	0.25	0.24	1	-0.67	57	58
GNA11	0.025	0.028	-10000	0	-0.4	2	2
MAPKKK cascade	-0.033	0.23	-10000	0	-0.63	49	49
E2/ER alpha (dimer)/PELP1/Src	-0.033	0.23	0.27	6	-0.55	54	60
ruffle organization	-0.019	0.054	-10000	0	-0.29	2	2
ROCK2	-0.02	0.061	-10000	0	-0.34	2	2
GNA14	0.025	0.028	-10000	0	-0.4	2	2
GNA15	0.022	0.048	-10000	0	-0.43	5	5
GNA13	0.027	0.005	-10000	0	-10000	0	0
MMP9	-0.011	0.26	0.37	83	-0.56	49	132
MMP2	-0.052	0.24	0.27	7	-0.57	59	66

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.007	0.14	-9999	-0.5	20	20
MAP3K8	0.027	0.002	-9999	-10000	0	0
FOS	-0.022	0.14	-9999	-0.5	20	20
PRKCA	0.026	0.007	-9999	-10000	0	0
PTPN7	0.021	0.055	-9999	-0.41	7	7
HRAS	0.026	0.02	-9999	-0.4	1	1
PRKCB	-0.068	0.18	-9999	-0.4	101	101
NRAS	0.025	0.029	-9999	-0.4	2	2
RAS family/GTP	0.049	0.025	-9999	-0.21	3	3
MAPK3	0.001	0.087	-9999	-0.55	5	5
MAP2K1	-0.059	0.16	-9999	-0.35	99	99
ELK1	0.027	0.006	-9999	-10000	0	0
BRAF	-0.051	0.15	-9999	-0.34	90	90
mol:GTP	0	0	-9999	-0.004	7	7
MAPK1	-0.021	0.15	-9999	-0.59	23	23
RAF1	-0.055	0.15	-9999	-0.35	94	94
KRAS	0.027	0.003	-9999	-10000	0	0

×

IL1-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
UBC13/UEV1A	0.02	0.002	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.027	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.013	0.045	-10000	0	-10000	0	0
IRAK/TOLLIP	0.031	0.006	-10000	0	-10000	0	0
IKBKB	0.024	0.009	-10000	0	-10000	0	0
IKBKG	0.026	0.02	-10000	0	-0.4	1	1
IL1 alpha/IL1R2	-0.14	0.18	-10000	0	-0.31	233	233
IL1A	-0.12	0.21	-10000	0	-0.43	149	149
IL1B	-0.022	0.1	-10000	0	-0.3	51	51
IRAK/TRAF6/p62/Atypical PKCs	0.062	0.028	-10000	0	-10000	0	0
IL1R2	-0.064	0.17	-10000	0	-0.4	97	97
IL1R1	0.021	0.052	-10000	0	-0.4	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.009	0.049	-10000	0	-10000	0	0
TOLLIP	0.027	0.003	-10000	0	-10000	0	0
TICAM2	0.015	0.054	-10000	0	-0.4	7	7
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.002	-10000	0	-10000	0	0
IKK complex/ELKS	0.025	0.052	-10000	0	-10000	0	0
JUN	-0.01	0.023	0.16	4	-10000	0	4
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.034	0.095	-10000	0	-0.35	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.035	0.15	-10000	0	-0.24	153	153
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.024	0.14	-10000	0	-0.22	147	147
IL1 beta fragment/IL1R1/IL1RAP	0.01	0.094	-10000	0	-0.23	57	57
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.008	0.024	0.17	4	-10000	0	4
IRAK1	0.014	0.002	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.018	0.13	-10000	0	-0.3	77	77
IRAK4	0.027	0.002	-10000	0	-10000	0	0
PRKCI	0.025	0.028	-10000	0	-0.4	2	2
TRAF6	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.039	0.008	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.051	-10000	0	-0.33	1	1
CHUK	0.026	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.01	0.094	-10000	0	-0.23	57	57
IL1 beta/IL1R2	-0.055	0.13	-10000	0	-0.25	144	144
IRAK/TRAF6/TAK1/TAB1/TAB2	0.038	0.009	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.022	0.086	-10000	0	-0.31	1	1
IRAK3	0.017	0.065	-10000	0	-0.4	11	11
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.028	0.099	-10000	0	-0.37	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.014	0.066	-10000	0	-0.24	8	8
IL1 alpha/IL1R1/IL1RAP	-0.052	0.15	-10000	0	-0.26	153	153
RELA	0.027	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.027	0.003	-10000	0	-10000	0	0
MYD88	0.027	0.003	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.045	0.014	-10000	0	-10000	0	0
IL1RAP	0.027	0.002	-10000	0	-10000	0	0
UBE2N	0.027	0.003	-10000	0	-10000	0	0
IRAK/TRAF6	0.005	0.08	-10000	0	-0.33	1	1
CASP1	0.026	0.02	-10000	0	-0.4	1	1
IL1RN/IL1R2	-0.082	0.16	-10000	0	-0.29	167	167
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.024	0.095	-10000	0	-0.22	47	47
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.004	0.063	-10000	0	-0.31	8	8
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
IL1RN	-0.043	0.16	-10000	0	-0.43	70	70
TRAF6/TAK1/TAB1/TAB2	0.039	0.008	-10000	0	-10000	0	0
MAP2K6	0.013	0.025	0.18	4	-10000	0	4

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.036	0.12	0.31	29	-10000	0	29
GNAI2	0.027	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.028	0.038	-10000	0	-0.26	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.088	0.19	-10000	0	-0.4	122	122
RhoA/GTP	-0.036	0.12	-10000	0	-0.32	29	29
negative regulation of cAMP metabolic process	-0.048	0.12	-10000	0	-0.23	116	116
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNA12	0.025	0.008	-10000	0	-10000	0	0
S1PR5	0.02	0.056	-10000	0	-0.43	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.049	0.12	-10000	0	-0.23	116	116
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13

×

Ephrin B reverse 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
EFNB2	0.021	0.011	-10000	0	-10000	0	0
EPHB2	0.024	0.031	-10000	0	-0.43	2	2
EFNB1	0.01	0.033	0.28	1	-0.29	4	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.024	0.13	-10000	0	-0.38	11	11
Ephrin B2/EPHB1-2	-0.007	0.1	0.25	2	-0.23	71	73
neuron projection morphogenesis	-0.033	0.12	-10000	0	-0.34	13	13
Ephrin B1/EPHB1-2/Tiam1	-0.036	0.14	0.24	1	-0.25	86	87
DNM1	0.024	0.045	0.36	1	-0.42	4	5
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.007	0.064	-10000	0	-0.39	11	11
YES1	-0.008	0.11	-10000	0	-0.62	12	12
Ephrin B1/EPHB1-2/NCK2	-0.012	0.12	0.26	2	-0.23	87	89
PI3K	0.032	0.079	-10000	0	-0.4	12	12
mol:GDP	-0.037	0.14	0.24	1	-0.24	87	88
ITGA2B	0.005	0.089	-10000	0	-0.43	18	18
endothelial cell proliferation	0.028	0.016	-10000	0	-10000	0	0
FYN	-0.005	0.11	-10000	0	-0.6	13	13
MAP3K7	-0.01	0.067	-10000	0	-0.42	11	11
FGR	-0.009	0.11	-10000	0	-0.61	14	14
TIAM1	-0.012	0.12	-10000	0	-0.4	41	41
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RGS3	0.027	0.003	-10000	0	-10000	0	0
cell adhesion	0.01	0.087	-10000	0	-0.38	12	12
LYN	-0.006	0.11	-10000	0	-0.6	14	14
Ephrin B1/EPHB1-2/Src Family Kinases	-0.009	0.092	-10000	0	-0.51	14	14
Ephrin B1/EPHB1-2	-0.01	0.073	-10000	0	-0.46	11	11
SRC	-0.007	0.1	-10000	0	-0.58	13	13
ITGB3	0.022	0.044	-10000	0	-0.4	5	5
EPHB1	-0.083	0.2	0.36	2	-0.42	112	114
EPHB4	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.028	0.016	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.022	0.075	-10000	0	-0.3	23	23
BLK	-0.044	0.12	-10000	0	-0.65	11	11
HCK	-0.01	0.1	-10000	0	-0.6	12	12
regulation of stress fiber formation	0.013	0.12	0.22	90	-0.26	2	92
MAPK8	-0.006	0.063	-10000	0	-0.37	11	11
Ephrin B1/EPHB1-2/RGS3	-0.013	0.12	0.26	2	-0.22	95	97
endothelial cell migration	0.021	0.088	0.25	26	-0.35	6	32
NCK2	0.027	0	-10000	0	-10000	0	0
PTPN13	0.01	0.076	-10000	0	-0.39	15	15
regulation of focal adhesion formation	0.013	0.12	0.22	90	-0.26	2	92
chemotaxis	0.014	0.12	0.22	95	-0.26	2	97
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.028	0.12	0.21	1	-0.36	12	13
angiogenesis	-0.009	0.073	-10000	0	-0.46	11	11
LCK	-0.008	0.11	-10000	0	-0.6	14	14

×

TCGA08_p53

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
CDKN2A	-0.059	0.13	0.27	2	-0.31	97	99
TP53	-0.018	0.063	-10000	0	-0.28	21	21
Senescence	-0.018	0.063	-10000	0	-0.27	21	21
Apoptosis	-0.018	0.063	-10000	0	-0.27	21	21
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.024	0.066	0.26	4	-0.19	3	7
MDM4	0.027	0.004	-10000	0	-10000	0	0

×

Wnt 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
Noncanonical Wnts/FZD	-0.025	0.097	0.17	1	-0.31	24	25
FZD6	0.023	0.01	-10000	0	-10000	0	0
WNT6	-0.002	0.1	-10000	0	-0.41	25	25
WNT4	0.007	0.088	-10000	0	-0.4	20	20
FZD3	0.022	0.033	0.36	2	-0.43	1	3
WNT5A	0.022	0.048	-10000	0	-0.43	5	5
WNT11	-0.065	0.18	-10000	0	-0.42	92	92

×

Signaling events mediated by PRL

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
CCNE1	0.027	0.031	0.36	2	-0.43	1	3
mol:Halofuginone	0.003	0	-10000	0	-10000	0	0
ITGA1	0.027	0.004	-10000	0	-10000	0	0
CDKN1A	0.007	0.048	-10000	0	-0.3	10	10
PRL-3/alpha Tubulin	0.023	0.12	0.26	34	-0.3	40	74
mol:Ca2+	-0.056	0.13	0.17	29	-0.3	82	111
AGT	-0.025	0.15	0.36	2	-0.43	53	55
CCNA2	-0.002	0.009	-10000	0	-10000	0	0
TUBA1B	0.027	0.002	-10000	0	-10000	0	0
EGR1	0.015	0.014	-10000	0	-0.27	1	1
CDK2/Cyclin E1	0.072	0.079	0.31	3	-10000	0	3
MAPK3	0.003	0.12	0.27	34	-0.3	41	75
PRL-2 /Rab GGTase beta	0.038	0.01	-10000	0	-10000	0	0
MAPK1	0.004	0.12	0.28	33	-0.3	40	73
PTP4A1	0.002	0.01	-10000	0	-10000	0	0
PTP4A3	0.01	0.16	0.36	34	-0.43	40	74
PTP4A2	0.026	0.006	-10000	0	-10000	0	0
ITGB1	0.004	0.12	0.27	34	-0.3	40	74
SRC	0.017	0.013	-10000	0	-10000	0	0
RAC1	0.025	0.071	0.3	17	-0.3	4	21
Rab GGTase beta/Rab GGTase alpha	0.037	0.012	-10000	0	-10000	0	0
PRL-1/ATF-5	0.082	0.082	-10000	0	-10000	0	0
RABGGTA	0.026	0.007	-10000	0	-10000	0	0
BCAR1	-0.021	0.083	0.15	40	-0.25	35	75
RHOC	0.026	0.085	0.31	22	-0.32	8	30
RHOA	0.027	0.079	0.31	21	-0.3	6	27
cell motility	0.048	0.11	0.31	19	-0.33	9	28
PRL-1/alpha Tubulin	0.084	0.082	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.022	0.12	0.26	32	-0.3	40	72
ROCK1	0.049	0.11	0.31	19	-0.34	7	26
RABGGTB	0.026	0.005	-10000	0	-10000	0	0
CDK2	0.027	0.002	-10000	0	-10000	0	0
mitosis	0.002	0.01	-10000	0	-10000	0	0
ATF5	0.027	0.003	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.019	0.072	0.54	3	-10000	0	3
VDR	0.027	0.003	-10000	0	-10000	0	0
FAM120B	0.027	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.046	0.11	-10000	0	-0.3	11	11
RXRs/LXRs/DNA/Oxysterols	-0.031	0.11	-10000	0	-0.4	7	7
MED1	0.027	0.017	0.36	1	-10000	0	1
mol:9cRA	0.003	0.006	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.036	0.11	0.17	1	-0.35	5	6
RXRs/NUR77	-0.038	0.14	-10000	0	-0.34	9	9
RXRs/PPAR	-0.057	0.12	-10000	0	-0.3	20	20
NCOR2	0.026	0.02	-10000	0	-0.4	1	1
VDR/VDR/Vit D3	0.02	0.002	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.059	0.033	0.24	1	-0.2	5	6
RARA	0.026	0.026	0.36	1	-0.4	1	2
NCOA1	0.027	0.001	-10000	0	-10000	0	0
VDR/VDR/DNA	0.027	0.003	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.045	0.031	0.22	1	-0.2	5	6
RARG	0.027	0.002	-10000	0	-10000	0	0
RPS6KB1	0.036	0.094	0.62	10	-0.38	1	11
RARs/THRs/DNA/SMRT	-0.037	0.11	0.17	1	-0.36	6	7
THRA	0.027	0.017	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	-0.04	0.13	-10000	0	-0.24	3	3
NR1H4	-0.21	0.2	-10000	0	-0.4	245	245
RXRs/LXRs/DNA	-0.017	0.14	-10000	0	-0.37	2	2
NR1H2	0.029	0.023	-10000	0	-0.39	1	1
NR1H3	0.03	0.011	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.032	0.13	-10000	0	-0.26	1	1
NR4A1	0.019	0.06	-10000	0	-0.42	8	8
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.16	0.15	-10000	0	-0.27	237	237
RXRG	-0.13	0.2	-10000	0	-0.39	168	168
RXR alpha/CCPG	0.04	0.019	-10000	0	-0.28	1	1
RXRA	0.029	0.023	-10000	0	-0.39	1	1
RXRB	0.03	0.011	-10000	0	-10000	0	0
THRB	-0.094	0.19	-10000	0	-0.4	128	128
PPARG	0.024	0.035	-10000	0	-0.4	3	3
PPARD	0.026	0.02	-10000	0	-0.4	1	1
TNF	-0.033	0.11	-10000	0	-0.78	3	3
mol:Oxysterols	0.003	0.006	-10000	0	-10000	0	0
cholesterol transport	-0.031	0.11	-10000	0	-0.4	7	7
PPARA	0.026	0.006	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.023	0.04	-10000	0	-0.4	4	4
RXRs/NUR77/BCL2	-0.08	0.13	-10000	0	-0.24	170	170
SREBF1	-0.023	0.091	-10000	0	-0.44	2	2
RXRs/RXRs/DNA/9cRA	-0.04	0.13	-10000	0	-0.24	3	3
ABCA1	-0.037	0.14	-10000	0	-0.88	6	6
RARs/THRs	-0.003	0.13	0.26	1	-0.39	2	3
RXRs/FXR	-0.17	0.17	-10000	0	-0.39	109	109
BCL2	0.012	0.059	-10000	0	-0.4	9	9

×

Canonical Wnt signaling pathway

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
HDAC1	0.026	0.01	-10000	0	-10000	0	0
AES	0.026	0.008	-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	0.018	-10000	0	-0.28	1	1
SMAD4	0.02	0.012	-10000	0	-10000	0	0
DKK2	-0.06	0.18	-10000	0	-0.43	84	84
TLE1	0.026	0.021	-10000	0	-0.39	1	1
MACF1	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.04	0.074	0.26	3	-0.46	1	4
WIF1	-0.074	0.17	-10000	0	-0.43	87	87
beta catenin/RanBP3	0.024	0.076	0.28	8	-0.4	1	9
KREMEN2	-0.02	0.14	0.36	2	-0.43	48	50
DKK1	-0.073	0.18	-10000	0	-0.43	93	93
beta catenin/beta TrCP1	0.051	0.072	0.26	2	-0.42	1	3
FZD1	0.026	0.021	-10000	0	-0.4	1	1
AXIN2	-0.002	0.12	0.59	9	-10000	0	9
AXIN1	0.026	0.02	-10000	0	-0.4	1	1
RAN	0.027	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.03	0.066	-10000	0	-0.51	5	5
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.023	0.15	-10000	0	-0.49	22	22
Axin1/APC/GSK3	0.053	0.066	0.21	10	-0.3	3	13
Axin1/APC/GSK3/beta catenin/Macf1	0.026	0.073	0.33	1	-0.37	2	3
HNF1A	0.025	0.029	-10000	0	-0.4	2	2
CTBP1	0.026	0.009	-10000	0	-10000	0	0
MYC	0.097	0.21	0.57	68	-10000	0	68
RANBP3	0.027	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.036	0.15	0.24	2	-0.27	123	125
NKD1	-0.26	0.22	0.36	4	-0.43	287	291
TCF4	0.019	0.024	-10000	0	-0.4	1	1
TCF3	0.026	0.008	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.061	0.037	-10000	0	-0.23	4	4
Ran/GTP	0.02	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.015	0.086	0.3	1	-0.38	7	8
LEF1	-0.029	0.15	-10000	0	-0.43	54	54
DVL1	0.025	0.054	-10000	0	-0.34	4	4
CSNK2A1	0.022	0.011	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.024	0.097	-10000	0	-0.58	6	6
DKK1/LRP6/Kremen 2	-0.041	0.15	0.24	2	-0.27	130	132
LRP6	0.027	0.004	-10000	0	-10000	0	0
CSNK1A1	0.026	0.009	-10000	0	-10000	0	0
NLK	0.027	0.005	-10000	0	-10000	0	0
CCND1	0.004	0.048	0.55	1	-10000	0	1
WNT1	0.017	0.039	-10000	0	-0.43	3	3
GSK3A	0.027	0.004	-10000	0	-10000	0	0
GSK3B	0.028	0.002	-10000	0	-10000	0	0
FRAT1	0.026	0.006	-10000	0	-10000	0	0
PPP2R5D	0.13	0.1	0.23	99	-0.25	3	102
APC	0.01	0.056	0.36	1	-10000	0	1
WNT1/LRP6/FZD1	0.039	0.049	0.2	5	-10000	0	5
CREBBP	0.026	0.008	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.037	0.24	0.43	1	-0.82	27	28
NCK1/PAK1/Dok-R	-0.028	0.096	-10000	0	-0.4	24	24
NCK1/Dok-R	0.009	0.26	-10000	0	-0.97	26	26
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
mol:beta2-estradiol	0.002	0.05	0.25	17	-10000	0	17
RELA	0.027	0.004	-10000	0	-10000	0	0
SHC1	0.028	0.005	-10000	0	-10000	0	0
Rac/GDP	0.018	0.006	-10000	0	-10000	0	0
F2	-0.13	0.22	0.29	18	-0.45	137	155
TNIP2	0.027	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	0.044	0.25	-10000	0	-0.89	28	28
FN1	0	0.11	-10000	0	-0.42	28	28
PLD2	-0.026	0.26	-10000	0	-0.98	28	28
PTPN11	0.027	0.003	-10000	0	-10000	0	0
GRB14	-0.007	0.11	-10000	0	-0.4	31	31
ELK1	0.01	0.25	-10000	0	-0.89	28	28
GRB7	0.033	0.044	0.36	8	-10000	0	8
PAK1	0.027	0.003	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.034	0.28	-10000	0	-0.95	28	28
CDKN1A	0.036	0.2	0.46	2	-0.63	22	24
ITGA5	0.024	0.037	-10000	0	-0.43	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.009	0.26	-10000	0	-0.97	26	26
CRK	0.023	0.01	-10000	0	-10000	0	0
mol:NO	0.049	0.2	0.42	8	-0.61	27	35
PLG	-0.053	0.27	-10000	0	-1	29	29
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.027	0.23	-10000	0	-0.79	27	27
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
ANGPT2	-0.027	0.21	0.39	2	-0.57	26	28
BMX	-0.071	0.28	-10000	0	-1.1	28	28
ANGPT1	0.012	0.23	-10000	0	-1.1	17	17
tube development	0.026	0.21	0.4	5	-0.68	22	27
ANGPT4	0.012	0.044	-10000	0	-0.42	4	4
response to hypoxia	-0.003	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.008	0.29	-10000	0	-1	28	28
alpha5/beta1 Integrin	0.038	0.028	-10000	0	-0.3	3	3
FGF2	-0.003	0.1	-10000	0	-0.39	30	30
STAT5A (dimer)	0.034	0.24	-10000	0	-0.78	22	22
mol:L-citrulline	0.049	0.2	0.42	8	-0.61	27	35
AGTR1	-0.12	0.2	-10000	0	-0.39	153	153
MAPK14	0	0.29	-10000	0	-1	29	29
Tie2/SHP2	0.015	0.22	-10000	0	-1	18	18
TEK	-0.011	0.23	-10000	0	-1.1	18	18
RPS6KB1	0.037	0.24	0.57	1	-0.8	26	27
Angiotensin II/AT1	-0.08	0.14	-10000	0	-0.27	153	153
Tie2/Ang1/GRB2	0.019	0.28	-10000	0	-1	28	28
MAPK3	-0.015	0.24	-10000	0	-0.9	28	28
MAPK1	-0.015	0.24	-10000	0	-0.91	27	27
Tie2/Ang1/GRB7	0.022	0.28	-10000	0	-1	28	28
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	-0.023	0.27	-10000	0	-0.99	28	28
PI3K	0.022	0.27	-10000	0	-0.96	27	27
FES	-0.01	0.29	-10000	0	-1	29	29
Crk/Dok-R	0.005	0.26	-10000	0	-0.96	26	26
Tie2/Ang1/ABIN2	0.019	0.28	-10000	0	-1	28	28
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.044	0.22	0.43	1	-0.73	27	28
STAT5A	0.027	0.004	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.057	0.24	0.48	8	-0.82	23	31
Tie2/Ang2	-0.012	0.25	0.48	1	-0.94	22	23
Tie2/Ang1	-0.021	0.29	-10000	0	-1.1	28	28
FOXO1	0.061	0.23	0.45	5	-0.78	21	26
ELF1	0.021	0.028	-10000	0	-10000	0	0
ELF2	-0.019	0.27	-10000	0	-1	27	27
mol:Choline	-0.023	0.25	-10000	0	-0.93	28	28
cell migration	-0.014	0.058	-10000	0	-0.22	27	27
FYN	0.018	0.23	0.44	2	-0.78	22	24
DOK2	0.015	0.049	-10000	0	-0.4	6	6
negative regulation of cell cycle	0.039	0.19	0.41	4	-0.57	22	26
ETS1	0.021	0.063	-10000	0	-0.28	17	17
PXN	0.061	0.21	0.44	10	-0.68	23	33
ITGB1	0.027	0.002	-10000	0	-10000	0	0
NOS3	0.045	0.22	0.45	6	-0.7	27	33
RAC1	0.025	0.008	-10000	0	-10000	0	0
TNF	0.022	0.063	-10000	0	-0.28	18	18
MAPKKK cascade	-0.023	0.25	-10000	0	-0.93	28	28
RASA1	0.027	0.005	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.02	0.29	-10000	0	-1	28	28
NCK1	0.027	0.002	-10000	0	-10000	0	0
vasculogenesis	0.051	0.18	0.39	11	-0.55	27	38
mol:Phosphatidic acid	-0.023	0.25	-10000	0	-0.93	28	28
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.049	0.2	0.42	8	-0.61	27	35
Rac1/GTP	0.03	0.21	-10000	0	-0.75	25	25
MMP2	-0.025	0.27	-10000	0	-1	28	28

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.003	0.074	-10000	0	-0.29	26	26
CRKL	0.026	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
DOCK1	0.027	0.005	-10000	0	-10000	0	0
ITGA4	0.01	0.083	-10000	0	-0.4	18	18
alpha4/beta7 Integrin/MAdCAM1	-0.082	0.16	-10000	0	-0.24	213	213
EPO	0.005	0.045	0.36	1	-0.43	3	4
alpha4/beta7 Integrin	0.016	0.092	-10000	0	-0.31	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.023	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.028	0.063	-10000	0	-0.28	18	18
EPO/EPOR (dimer)	0.033	0.035	0.26	1	-0.3	4	5
lamellipodium assembly	0.005	0.081	-10000	0	-0.44	5	5
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
PI3K	0.039	0.008	-10000	0	-10000	0	0
ARF6	0.025	0.007	-10000	0	-10000	0	0
JAK2	0.013	0.058	-10000	0	-0.44	3	3
PXN	0.027	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
MADCAM1	-0.18	0.21	-10000	0	-0.4	211	211
cell adhesion	-0.082	0.16	-10000	0	-0.24	213	213
CRKL/CBL	0.039	0.009	-10000	0	-10000	0	0
ITGB1	0.027	0.002	-10000	0	-10000	0	0
SRC	0.001	0.055	0.18	1	-0.4	6	7
ITGB7	0.01	0.083	-10000	0	-0.4	18	18
RAC1	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.036	0.081	-10000	0	-0.31	21	21
p130Cas/Crk/Dock1	0.051	0.08	-10000	0	-0.34	6	6
VCAM1	0.016	0.065	-10000	0	-0.4	11	11
RHOA	0.027	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.058	0.054	-10000	0	-0.21	16	16
BCAR1	-0.014	0.05	0.18	1	-0.38	6	7
EPOR	0.026	0.022	-10000	0	-0.43	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.027	0.004	-10000	0	-10000	0	0
GIT1	0.026	0.02	-10000	0	-0.4	1	1
Rac1/GTP	0.005	0.083	-10000	0	-0.46	5	5

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.006	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.021	0.079	-10000	0	-0.22	41	41
regulation of S phase of mitotic cell cycle	0.006	0.042	-10000	0	-0.2	15	15
GNAO1	-0.088	0.19	-10000	0	-0.4	122	122
HRAS	0.026	0.02	-10000	0	-0.4	1	1
SHBG/T-DHT	0.011	0.033	-10000	0	-0.32	4	4
PELP1	0.023	0.01	-10000	0	-10000	0	0
AKT1	0.007	0.002	-10000	0	-10000	0	0
MAP2K1	0.048	0.097	0.18	150	-10000	0	150
T-DHT/AR	0.002	0.069	-10000	0	-0.28	26	26
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.009	7	7
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
mol:GDP	-0.014	0.071	-10000	0	-0.3	24	24
cell proliferation	0.043	0.11	0.24	6	-0.36	4	10
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
FOS	0.035	0.12	0.26	1	-0.74	7	8
mol:Ca2+	-0.013	0.029	-10000	0	-0.078	44	44
MAPK3	0.048	0.098	0.21	21	-0.31	1	22
MAPK1	0.021	0.1	0.21	1	-0.41	15	16
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	7	7
cAMP biosynthetic process	0.006	0.038	-10000	0	-0.29	4	4
GNG2	0.009	0.081	-10000	0	-0.4	17	17
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	7	7
HRAS/GTP	0.02	0.051	-10000	0	-0.19	17	17
actin cytoskeleton reorganization	0.034	0.02	-10000	0	-0.19	1	1
SRC	0.017	0.013	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	7	7
PI3K	0.036	0.008	-10000	0	-10000	0	0
apoptosis	-0.043	0.094	0.35	8	-0.28	1	9
T-DHT/AR/PELP1	0.015	0.062	-10000	0	-0.23	26	26
HRAS/GDP	-0.003	0.072	-10000	0	-0.29	24	24
CREB1	0.043	0.098	0.28	1	-0.38	8	9
RAC1-CDC42/GTP	0.043	0.024	-10000	0	-0.19	1	1
AR	-0.004	0.099	-10000	0	-0.4	26	26
GNB1	0.026	0.007	-10000	0	-10000	0	0
RAF1	0.063	0.097	0.18	142	-10000	0	142
RAC1-CDC42/GDP	0.036	0.086	-10000	0	-0.33	15	15
T-DHT/AR/PELP1/Src	0.019	0.053	-10000	0	-0.21	17	17
MAP2K2	0.048	0.098	0.17	153	-0.34	1	154
T-DHT/AR/PELP1/Src/PI3K	0.006	0.042	-10000	0	-0.2	15	15
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
SHBG	0.011	0.054	-10000	0	-0.52	4	4
Gi family/GNB1/GNG2/GDP	-0.077	0.19	-10000	0	-0.38	100	100
mol:T-DHT	0	0.001	-10000	0	-0.005	7	7
RAC1	0.025	0.008	-10000	0	-10000	0	0
GNRH1	0.005	0.004	-10000	0	-10000	0	0
Gi family/GTP	-0.05	0.11	-10000	0	-0.3	47	47
CDC42	0.025	0.021	-10000	0	-0.4	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.026	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.029	0.096	-10000	0	-0.3	22	22
NT3 (dimer)/TRKC	-0.023	0.13	-10000	0	-0.29	81	81
NT3 (dimer)/TRKB	-0.095	0.18	-10000	0	-0.3	186	186
SHC/Grb2/SOS1/GAB1/PI3K	0.029	0.01	-10000	0	-10000	0	0
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1
BDNF	0.014	0.076	-10000	0	-0.43	13	13
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
NTRK1	0.018	0.044	-10000	0	-0.43	4	4
NTRK2	-0.093	0.19	-10000	0	-0.4	127	127
NTRK3	-0.055	0.16	-10000	0	-0.4	79	79
NT-4/5 (dimer)/TRKB	-0.11	0.18	-10000	0	-0.3	199	199
neuron apoptosis	0.094	0.16	0.39	71	-10000	0	71
SHC 2-3/Grb2	-0.1	0.17	-10000	0	-0.42	71	71
SHC1	0.027	0.004	-10000	0	-10000	0	0
SHC2	-0.1	0.17	-10000	0	-0.43	73	73
SHC3	-0.1	0.16	-10000	0	-0.43	67	67
STAT3 (dimer)	0.031	0.018	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.025	0.13	-10000	0	-0.24	116	116
RIN/GDP	-0.005	0.08	0.2	6	-0.25	6	12
GIPC1	0.026	0.02	-10000	0	-0.4	1	1
KRAS	0.027	0.003	-10000	0	-10000	0	0
DNAJA3	-0.068	0.12	-10000	0	-0.28	104	104
RIN/GTP	0.009	0.016	-10000	0	-0.3	1	1
CCND1	0.017	0.029	-10000	0	-0.33	3	3
MAGED1	0.027	0.003	-10000	0	-10000	0	0
PTPN11	0.027	0.003	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.018	0.091	-10000	0	-0.44	19	19
SHC/GRB2/SOS1	0.053	0.013	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.007	0.1	-10000	0	-0.24	66	66
TRKA/NEDD4-2	0.026	0.039	-10000	0	-0.3	5	5
ELMO1	0.022	0.035	-10000	0	-0.4	3	3
RhoG/GTP/ELMO1/DOCK1	0.031	0.025	-10000	0	-0.23	3	3
NGF	0.008	0.079	-10000	0	-0.4	16	16
HRAS	0.026	0.02	-10000	0	-0.4	1	1
DOCK1	0.027	0.005	-10000	0	-10000	0	0
GAB2	0.027	0.003	-10000	0	-10000	0	0
RIT2	-0.012	0.023	-10000	0	-0.43	1	1
RIT1	0.027	0.004	-10000	0	-10000	0	0
FRS2	0.027	0.003	-10000	0	-10000	0	0
DNM1	0.024	0.046	0.36	1	-0.43	4	5
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	-0.051	0.13	-10000	0	-0.28	98	98
mol:GDP	-0.013	0.11	0.25	6	-0.36	10	16
NGF (dimer)	0.008	0.079	-10000	0	-0.4	16	16
RhoG/GDP	0.016	0.025	-10000	0	-0.28	3	3
RIT1/GDP	-0.001	0.085	0.2	7	-0.25	8	15
TIAM1	-0.012	0.12	-10000	0	-0.4	41	41
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.039	0.13	-10000	0	-0.24	139	139
KIDINS220/CRKL/C3G	0.038	0.018	-10000	0	-0.28	1	1
SHC/RasGAP	0.039	0.009	-10000	0	-10000	0	0
FRS2 family/SHP2	0.055	0.013	0.24	1	-10000	0	1
SHC/GRB2/SOS1/GAB1	0.066	0.019	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.003	-10000	0	-10000	0	0
NT3 (dimer)	0.018	0.056	-10000	0	-0.4	8	8
RAP1/GDP	-0.004	0.07	-10000	0	-0.22	5	5
KIDINS220/CRKL	0.026	0.006	-10000	0	-10000	0	0
BDNF (dimer)	0.014	0.076	-10000	0	-0.43	13	13
ubiquitin-dependent protein catabolic process	0.026	0.063	-10000	0	-0.24	21	21
Schwann cell development	-0.027	0.029	-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	0.041	0.25	1	-0.24	1	2
RAP1B	0.027	0.002	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.059	0.13	-10000	0	-0.37	29	29
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	-0.018	0.1	-10000	0	-0.44	14	14
STAT3	0.031	0.018	-10000	0	-10000	0	0
axon guidance	-0.062	0.12	-10000	0	-0.36	29	29
MAPK3	-0.02	0.087	0.18	7	-0.26	7	14
MAPK1	-0.019	0.084	0.18	4	-0.32	2	6
CDC42/GDP	0	0.085	0.19	9	-0.25	7	16
NTF3	0.018	0.056	-10000	0	-0.4	8	8
NTF4	-0.018	0.091	-10000	0	-0.44	19	19
NGF (dimer)/TRKA/FAIM	0.038	0.062	-10000	0	-0.24	20	20
PI3K	0.039	0.008	-10000	0	-10000	0	0
FRS3	0.028	0.016	0.36	1	-10000	0	1
FAIM	0.027	0.003	-10000	0	-10000	0	0
GAB1	0.027	0.005	-10000	0	-10000	0	0
RASGRF1	-0.083	0.14	-10000	0	-0.29	111	111
SOS1	0.027	0.002	-10000	0	-10000	0	0
MCF2L	-0.032	0.094	-10000	0	-0.25	69	69
RGS19	0.017	0.013	-10000	0	-10000	0	0
CDC42	0.025	0.021	-10000	0	-0.4	1	1
RAS family/GTP	0.006	0.072	-10000	0	-0.36	3	3
Rac1/GDP	-0.006	0.081	0.19	6	-0.25	8	14
NGF (dimer)/TRKA/GRIT	0.022	0.057	-10000	0	-0.24	20	20
neuron projection morphogenesis	-0.051	0.14	-10000	0	-0.71	2	2
NGF (dimer)/TRKA/NEDD4-2	0.027	0.064	-10000	0	-0.24	21	21
MAP2K1	0.018	0.03	-10000	0	-10000	0	0
NGFR	-0.081	0.18	-10000	0	-0.4	114	114
NGF (dimer)/TRKA/GIPC/GAIP	0.011	0.038	-10000	0	-0.2	10	10
RAS family/GTP/PI3K	0.023	0.02	-10000	0	-0.2	1	1
FRS2 family/SHP2/GRB2/SOS1	0.078	0.021	0.25	1	-10000	0	1
NRAS	0.025	0.029	-10000	0	-0.4	2	2
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
PRKCI	0.025	0.028	-10000	0	-0.4	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	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.048	0.15	-10000	0	-0.56	32	32
RASA1	0.027	0.005	-10000	0	-10000	0	0
TRKA/c-Abl	0.035	0.033	-10000	0	-0.3	4	4
SQSTM1	0.027	0.003	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.022	0.13	-10000	0	-0.22	138	138
NGF (dimer)/TRKA/p62/Atypical PKCs	0.058	0.067	-10000	0	-0.26	5	5
MATK	-0.021	0.13	-10000	0	-0.4	51	51
NEDD4L	0.02	0.023	-10000	0	-0.4	1	1
RAS family/GDP	-0.026	0.046	-10000	0	-0.23	1	1
NGF (dimer)/TRKA	-0.064	0.14	-10000	0	-0.29	113	113
Rac1/GTP	-0.066	0.1	-10000	0	-0.28	47	47
FRS2 family/SHP2/CRK family	0.065	0.034	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.005	0.001	-10000	0	-10000	0	0
ADCY5	-0.1	0.11	-10000	0	-0.23	187	187
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	1	-0.25	11	12
ADCY2	-0.024	0.063	-10000	0	-0.23	37	37
ADCY3	-0.006	0.001	-10000	0	-10000	0	0
ADCY8	-0.011	0.03	0.21	1	-0.26	6	7
PRKCE	0.007	0.001	-10000	0	-10000	0	0
ADCY9	-0.007	0.015	-10000	0	-0.23	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.012	0.074	0.2	13	-0.22	3	16

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	0.024	0.094	-10000	0	-0.37	4	4
HDAC1	0.024	0.006	-10000	0	-10000	0	0
AES	0.026	0.004	-10000	0	-10000	0	0
FBXW11	0.027	0.004	-10000	0	-10000	0	0
DTX1	0.022	0.044	-10000	0	-0.4	5	5
LRP6/FZD1	0.038	0.018	-10000	0	-0.28	1	1
TLE1	0.026	0.02	-10000	0	-0.4	1	1
AP1	-0.078	0.095	0.18	3	-0.29	41	44
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	0.04	0.083	-10000	0	-0.57	7	7
NICD/RBPSUH	0.025	0.093	-10000	0	-0.37	3	3
WIF1	-0.074	0.17	-10000	0	-0.43	87	87
NOTCH1	0.007	0.092	-10000	0	-0.38	17	17
PSENEN	0.026	0.02	-10000	0	-0.4	1	1
KREMEN2	-0.02	0.14	0.36	2	-0.43	48	50
DKK1	-0.073	0.18	-10000	0	-0.43	93	93
beta catenin/beta TrCP1	0.089	0.076	0.26	6	-0.29	1	7
APH1B	0.026	0.006	-10000	0	-10000	0	0
APH1A	0.027	0.004	-10000	0	-10000	0	0
AXIN1	-0.027	0.069	-10000	0	-0.41	8	8
CtBP/CBP/TCF1/TLE1/AES	0.018	0.027	-10000	0	-0.29	1	1
PSEN1	0.026	0.007	-10000	0	-10000	0	0
FOS	0.023	0.035	-10000	0	-0.4	3	3
JUN	0.027	0.005	-10000	0	-10000	0	0
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.078	0.079	0.25	10	-0.31	1	11
MAPK3	0.026	0.02	-10000	0	-0.4	1	1
DKK2/LRP6/Kremen 2	-0.036	0.15	0.24	2	-0.27	123	125
HNF1A	0.025	0.028	-10000	0	-0.39	2	2
CTBP1	0.026	0.005	-10000	0	-10000	0	0
MYC	0.024	0.038	-10000	0	-10000	0	0
NKD1	-0.26	0.22	0.36	4	-0.43	287	291
FZD1	0.025	0.021	-10000	0	-0.4	1	1
NOTCH1 precursor/Deltex homolog 1	0.023	0.095	-10000	0	-0.36	15	15
apoptosis	-0.077	0.094	0.18	3	-0.29	41	44
Delta 1/NOTCHprecursor	0.023	0.095	-10000	0	-0.37	4	4
DLL1	0.024	0.035	-10000	0	-0.4	3	3
PPARD	0.029	0.071	-10000	0	-0.99	2	2
Gamma Secretase	0.07	0.032	-10000	0	-10000	0	0
APC	-0.047	0.11	-10000	0	-0.4	33	33
DVL1	0.002	0.083	-10000	0	-0.37	16	16
CSNK2A1	0.023	0.011	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.041	0.15	0.24	2	-0.27	130	132
LRP6	0.027	0.004	-10000	0	-10000	0	0
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
NLK	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.019	0.11	-10000	0	-0.82	7	7
WNT1	0.01	0.041	-10000	0	-0.43	3	3
Axin1/APC/beta catenin	0.021	0.11	-10000	0	-0.47	9	9
DKK2	-0.06	0.18	-10000	0	-0.43	84	84
NOTCH1 precursor/DVL1	0.004	0.13	-10000	0	-0.52	17	17
GSK3B	0.027	0.002	-10000	0	-10000	0	0
FRAT1	0.026	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.024	0.095	-10000	0	-0.36	15	15
PPP2R5D	0.13	0.1	0.24	59	-0.28	4	63
MAPK1	0.026	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.004	0.12	-10000	0	-0.24	82	82
RBPJ	0.027	0.004	-10000	0	-10000	0	0
CREBBP	0.029	0.005	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.001	0.1	0.22	1	-0.35	19	20
TBX21	-0.1	0.4	-10000	0	-1.2	44	44
B2M	0.022	0.026	-10000	0	-0.4	1	1
TYK2	0.018	0.033	-10000	0	-10000	0	0
IL12RB1	0.003	0.09	-10000	0	-0.42	17	17
GADD45B	-0.044	0.29	-10000	0	-0.89	30	30
IL12RB2	0.012	0.063	-10000	0	-0.43	7	7
GADD45G	-0.044	0.29	-10000	0	-0.86	32	32
natural killer cell activation	0	0.019	0.045	7	-0.041	37	44
RELB	0.027	0.003	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
IL18	0.025	0.031	-10000	0	-0.39	2	2
IL2RA	0.017	0.065	-10000	0	-0.4	11	11
IFNG	-0.024	0.13	-10000	0	-0.43	44	44
STAT3 (dimer)	-0.046	0.28	-10000	0	-0.74	43	43
HLA-DRB5	0.001	0.002	-10000	0	-0.022	2	2
FASLG	-0.11	0.41	0.58	1	-1.2	46	47
NF kappa B2 p52/RelB	-0.068	0.33	-10000	0	-0.92	43	43
CD4	0.011	0.081	-10000	0	-0.4	17	17
SOCS1	0.017	0.067	-10000	0	-0.43	10	10
EntrezGene:6955	0	0.009	-10000	0	-0.037	23	23
CD3D	0.012	0.073	-10000	0	-0.4	13	13
CD3E	0.01	0.08	-10000	0	-0.4	16	16
CD3G	-0.009	0.12	-10000	0	-0.4	36	36
IL12Rbeta2/JAK2	0.023	0.069	-10000	0	-0.32	10	10
CCL3	-0.081	0.34	-10000	0	-0.96	39	39
CCL4	-0.076	0.33	-10000	0	-0.96	38	38
HLA-A	-0.001	0.009	-10000	0	-0.039	21	21
IL18/IL18R	0.046	0.093	-10000	0	-0.25	34	34
NOS2	-0.093	0.39	-10000	0	-1.2	42	42
IL12/IL12R/TYK2/JAK2/SPHK2	0.003	0.1	0.22	1	-0.35	18	19
IL1R1	-0.085	0.35	-10000	0	-1	41	41
IL4	-0.001	0.035	-10000	0	-10000	0	0
JAK2	0.015	0.049	-10000	0	-0.43	3	3
EntrezGene:6957	0	0.009	-10000	0	-0.037	23	23
TCR/CD3/MHC I/CD8	-0.069	0.29	-10000	0	-0.87	44	44
RAB7A	-0.031	0.25	-10000	0	-0.78	25	25
lysosomal transport	-0.027	0.24	-10000	0	-0.73	25	25
FOS	-0.073	0.31	-10000	0	-0.91	40	40
STAT4 (dimer)	-0.047	0.31	0.41	2	-0.85	42	44
STAT5A (dimer)	-0.082	0.34	-10000	0	-0.88	48	48
GZMA	-0.13	0.45	-10000	0	-1.3	53	53
GZMB	-0.1	0.34	-10000	0	-0.96	40	40
HLX	0.026	0.02	-10000	0	-0.4	1	1
LCK	-0.09	0.36	-10000	0	-0.96	47	47
TCR/CD3/MHC II/CD4	-0.023	0.16	-10000	0	-0.47	36	36
IL2/IL2R	0.048	0.073	-10000	0	-0.3	16	16
MAPK14	-0.046	0.3	-10000	0	-0.92	31	31
CCR5	-0.052	0.31	-10000	0	-1	27	27
IL1B	-0.03	0.14	-10000	0	-0.42	50	50
STAT6	0.003	0.096	0.22	1	-10000	0	1
STAT4	0.006	0.093	-10000	0	-0.4	23	23
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.026	0.021	-10000	0	-0.43	1	1
NFKB1	0.027	0.005	-10000	0	-10000	0	0
NFKB2	0.026	0.006	-10000	0	-10000	0	0
IL12B	0.01	0.054	-10000	0	-0.42	4	4
CD8A	-0.006	0.11	-10000	0	-0.4	33	33
CD8B	0.011	0.076	-10000	0	-0.4	14	14
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.001	0.1	0.35	19	-0.22	1	20
IL2RB	0.017	0.062	-10000	0	-0.4	10	10
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.28	0.41	2	-0.77	42	44
IL2RG	0.025	0.028	-10000	0	-0.4	2	2
IL12	0.02	0.069	-10000	0	-0.3	10	10
STAT5A	0.027	0.004	-10000	0	-10000	0	0
CD247	0.013	0.073	-10000	0	-0.4	13	13
IL2	-0.006	0.02	-10000	0	-10000	0	0
SPHK2	0.026	0.02	-10000	0	-0.4	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.012	0.06	-10000	0	-0.42	6	6
IL12/IL12R/TYK2/JAK2	-0.091	0.38	-10000	0	-1	46	46
MAP2K3	-0.067	0.32	-10000	0	-0.89	42	42
RIPK2	0.023	0.01	-10000	0	-10000	0	0
MAP2K6	-0.041	0.3	-10000	0	-0.88	33	33
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.001	0.002	-10000	0	-0.026	2	2
IL18RAP	0.004	0.098	-10000	0	-0.4	24	24
IL12Rbeta1/TYK2	0.018	0.078	-10000	0	-0.32	17	17
EOMES	-0.054	0.28	-10000	0	-1.1	28	28
STAT1 (dimer)	-0.042	0.27	-10000	0	-0.75	38	38
T cell proliferation	-0.025	0.23	0.36	2	-0.63	37	39
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.019	0.062	-10000	0	-0.4	9	9
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.032	0.25	-10000	0	-0.7	36	36
ATF2	-0.042	0.28	-10000	0	-0.85	30	30

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.002	0.1	-10000	0	-0.38	14	14
Syndecan-3/Neurocan	0.006	0.09	-10000	0	-0.37	23	23
POMC	0.008	0.086	-10000	0	-0.4	19	19
EGFR	0.024	0.021	-10000	0	-0.4	1	1
Syndecan-3/EGFR	0.007	0.088	-10000	0	-0.36	22	22
AGRP	-0.004	0.041	-10000	0	-0.43	3	3
NCSTN	0.027	0.004	-10000	0	-10000	0	0
PSENEN	0.026	0.02	-10000	0	-0.4	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	0.036	-10000	0	-0.43	2	2
long-term memory	0.026	0.089	-10000	0	-0.35	23	23
Syndecan-3/IL8	-0.12	0.14	0.23	1	-0.44	27	28
PSEN1	0.025	0.007	-10000	0	-10000	0	0
Src/Cortactin	0.024	0.02	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
limb bud formation	-0.006	0.086	-10000	0	-0.38	23	23
MC4R	-0.008	0.043	-10000	0	-0.43	4	4
SRC	0.017	0.013	-10000	0	-10000	0	0
PTN	-0.042	0.16	-10000	0	-0.4	72	72
FGFR/FGF/Syndecan-3	-0.006	0.087	-10000	0	-0.38	23	23
neuron projection morphogenesis	0.024	0.12	-10000	0	-0.38	14	14
Syndecan-3/AgRP	0.005	0.091	-10000	0	-0.37	23	23
Syndecan-3/AgRP/MC4R	0.009	0.091	-10000	0	-0.34	24	24
Fyn/Cortactin	0.039	0.008	-10000	0	-10000	0	0
SDC3	-0.007	0.088	-10000	0	-0.38	23	23
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.12	0.14	0.23	1	-0.44	27	28
IL8	-0.24	0.23	0.36	1	-0.43	260	261
Syndecan-3/Fyn/Cortactin	0.027	0.091	-10000	0	-0.35	23	23
Syndecan-3/CASK	-0.008	0.084	-10000	0	-0.36	23	23
alpha-MSH/MC4R	0.011	0.069	-10000	0	-0.28	23	23
Gamma Secretase	0.07	0.032	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.009	0.13	-10000	0	-0.74	5	5
MKNK1	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.008	0.088	-10000	0	-0.3	22	22
ATF2/c-Jun	0.004	0.065	-10000	0	-0.32	1	1
MAPK11	0.007	0.091	-10000	0	-0.31	24	24
MITF	-0.007	0.1	-10000	0	-0.34	29	29
MAPKAPK5	-0.001	0.097	-10000	0	-0.33	29	29
KRT8	0	0.094	-10000	0	-0.33	28	28
MAPKAPK3	0.027	0.004	-10000	0	-10000	0	0
MAPKAPK2	0.027	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.008	0.13	-10000	0	-0.43	25	25
CEBPB	-0.003	0.075	-10000	0	-0.33	16	16
SLC9A1	-0.003	0.1	-10000	0	-0.36	27	27
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.002	0.094	-10000	0	-0.32	25	25
p38alpha-beta/MNK1	0.025	0.11	-10000	0	-0.35	23	23
JUN	0.003	0.063	-10000	0	-0.32	1	1
PPARGC1A	-0.036	0.14	-10000	0	-0.39	34	34
USF1	0.003	0.089	-10000	0	-0.33	24	24
RAB5/GDP/GDI1	0.007	0.075	-10000	0	-0.25	23	23
NOS2	-0.035	0.22	-10000	0	-0.91	25	25
DDIT3	-0.001	0.097	-10000	0	-0.34	28	28
RAB5A	0.026	0.02	-10000	0	-0.4	1	1
HSPB1	0.002	0.093	0.28	15	-0.28	25	40
p38alpha-beta/HBP1	0.023	0.11	-10000	0	-0.35	22	22
CREB1	0.001	0.1	-10000	0	-0.37	26	26
RAB5/GDP	0.019	0.014	-10000	0	-0.28	1	1
EIF4E	-0.005	0.087	-10000	0	-0.32	23	23
RPS6KA4	-0.001	0.096	-10000	0	-0.33	29	29
PLA2G4A	-0.024	0.11	-10000	0	-0.36	20	20
GDI1	0	0.094	-10000	0	-0.33	28	28
TP53	-0.017	0.11	-10000	0	-0.42	23	23
RPS6KA5	-0.003	0.1	-10000	0	-0.37	26	26
ESR1	-0.023	0.13	-10000	0	-0.4	29	29
HBP1	0.026	0.005	-10000	0	-10000	0	0
MEF2C	-0.008	0.11	-10000	0	-0.35	28	28
MEF2A	-0.002	0.1	-10000	0	-0.35	28	28
EIF4EBP1	-0.004	0.1	-10000	0	-0.38	26	26
KRT19	-0.001	0.096	-10000	0	-0.33	29	29
ELK4	0.003	0.089	-10000	0	-0.33	24	24
ATF6	0.003	0.089	-10000	0	-0.33	24	24
ATF1	0.001	0.1	-10000	0	-0.37	26	26
p38alpha-beta/MAPKAPK2	0.028	0.1	-10000	0	-0.36	20	20
p38alpha-beta/MAPKAPK3	0.025	0.11	-10000	0	-0.35	23	23

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.088	0.19	-10000	0	-0.4	122	122
CDC42/GTP	-0.04	0.13	-10000	0	-0.35	31	31
PLCG1	-0.035	0.1	-10000	0	-0.36	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.027	0.004	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
G12/G13	0.036	0.013	-10000	0	-10000	0	0
cell migration	-0.04	0.12	-10000	0	-0.34	31	31
S1PR5	0.02	0.056	-10000	0	-0.43	7	7
S1PR4	0.017	0.062	-10000	0	-0.4	10	10
MAPK3	-0.055	0.12	-10000	0	-0.36	33	33
MAPK1	-0.045	0.12	-10000	0	-0.38	22	22
S1P/S1P5/Gi	-0.049	0.12	-10000	0	-0.23	116	116
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
CDC42/GDP	0.018	0.015	-10000	0	-0.28	1	1
S1P/S1P5/G12	0.028	0.038	-10000	0	-0.26	7	7
RHOA	0.028	0.062	0.18	49	-10000	0	49
S1P/S1P4/Gi	-0.053	0.13	-10000	0	-0.36	35	35
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
S1P/S1P4/G12/G13	0.041	0.039	-10000	0	-0.21	8	8
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.025	0.021	-10000	0	-0.4	1	1

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.014	0.039	-10000	0	-0.24	3	3
NFATC2	-0.014	0.044	-10000	0	-0.25	9	9
NFATC3	-0.014	0.038	-10000	0	-10000	0	0
CD40LG	-0.064	0.21	0.36	1	-0.57	27	28
PTGS2	-0.062	0.21	0.36	1	-0.55	33	34
JUNB	0.025	0.028	-10000	0	-0.4	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	0.008	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	0.22	-10000	0	-0.43	294	294
CREM	0.027	0.001	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.013	0.14	-10000	0	-0.41	4	4
FOS	0.006	0.042	-10000	0	-0.4	3	3
IFNG	-0.068	0.22	0.36	1	-0.56	32	33
AP-1/NFAT1-c-4	-0.057	0.21	-10000	0	-0.58	18	18
FASLG	-0.061	0.2	0.36	1	-0.55	20	21
NFAT1-c-4/ICER1	-0.02	0.077	-10000	0	-0.32	1	1
IL2RA	-0.055	0.2	0.36	1	-0.57	15	16
FKBP12/FK506	0.017	0.008	-10000	0	-10000	0	0
CSF2	-0.12	0.25	0.36	1	-0.55	56	57
JunB/Fra1/NFAT1-c-4	-0.1	0.16	-10000	0	-0.34	49	49
IL4	-0.055	0.19	0.36	1	-0.56	12	13
IL2	-0.015	0.14	-10000	0	-0.82	13	13
IL3	0.001	0.081	-10000	0	-0.62	7	7
FKBP1A	0.022	0.011	-10000	0	-10000	0	0
BATF3	0.022	0.047	-10000	0	-0.42	5	5
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.027	0.005	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.008	0.1	-10000	0	-0.46	19	19
NFATC2	-0.004	0.12	-10000	0	-0.6	8	8
NFATC3	-0.022	0.068	-10000	0	-0.3	4	4
CD40LG	-0.19	0.28	-10000	0	-0.81	38	38
ITCH	0.018	0.019	-10000	0	-10000	0	0
CBLB	0.029	0.028	-10000	0	-0.49	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.21	-10000	0	-0.81	20	20
JUNB	0.025	0.028	-10000	0	-0.4	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.037	0.022	-10000	0	-0.24	2	2
T cell anergy	0.038	0.055	-10000	0	-0.32	1	1
TLE4	-0.004	0.09	-10000	0	-0.49	7	7
Jun/NFAT1-c-4/p21SNFT	-0.084	0.18	-10000	0	-0.76	11	11
AP-1/NFAT1-c-4	-0.21	0.27	-10000	0	-0.88	29	29
IKZF1	-0.017	0.14	-10000	0	-0.66	17	17
T-helper 2 cell differentiation	-0.065	0.17	-10000	0	-0.7	15	15
AP-1/NFAT1	-0.035	0.1	-10000	0	-0.4	7	7
CALM1	0.034	0.016	-10000	0	-10000	0	0
EGR2	-0.046	0.18	-10000	0	-1.1	9	9
EGR3	-0.046	0.18	-10000	0	-0.92	12	12
NFAT1/FOXP3	-0.001	0.12	-10000	0	-0.48	14	14
EGR1	0.027	0.021	-10000	0	-0.39	1	1
JUN	-0.031	0.045	-10000	0	-10000	0	0
EGR4	-0.054	0.17	-10000	0	-0.42	80	80
mol:Ca2+	0.009	0.01	-10000	0	-10000	0	0
GBP3	-0.022	0.15	-10000	0	-0.62	22	22
FOSL1	-0.27	0.22	-10000	0	-0.43	294	294
NFAT1-c-4/MAF/IRF4	-0.091	0.2	-10000	0	-0.8	18	18
DGKA	-0.004	0.085	-10000	0	-0.44	7	7
CREM	0.027	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.048	0.16	-10000	0	-0.76	9	9
CTLA4	-0.016	0.12	-10000	0	-0.52	14	14
NFAT1-c-4 (dimer)/EGR1	-0.044	0.16	-10000	0	-0.82	7	7
NFAT1-c-4 (dimer)/EGR4	-0.077	0.18	-10000	0	-0.88	7	7
FOS	-0.032	0.055	-10000	0	-0.42	3	3
IFNG	-0.064	0.19	-10000	0	-0.74	16	16
T cell activation	-0.028	0.14	-10000	0	-0.6	2	2
MAF	0.016	0.068	-10000	0	-0.4	12	12
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.044	0.15	0.81	11	-10000	0	11
TNF	-0.07	0.16	-10000	0	-0.83	7	7
FASLG	-0.11	0.37	-10000	0	-1.2	40	40
TBX21	-0.005	0.1	-10000	0	-0.4	27	27
BATF3	0.022	0.047	-10000	0	-0.42	5	5
PRKCQ	0.018	0.05	-10000	0	-0.39	4	4
PTPN1	-0.003	0.083	-10000	0	-0.45	6	6
NFAT1-c-4/ICER1	-0.047	0.16	-10000	0	-0.82	7	7
GATA3	0.023	0.045	-10000	0	-0.4	5	5
T-helper 1 cell differentiation	-0.064	0.18	-10000	0	-0.69	19	19
IL2RA	-0.11	0.21	-10000	0	-0.74	26	26
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.004	0.083	-10000	0	-0.45	6	6
E2F1	0.024	0.057	0.36	8	-0.42	2	10
PPARG	0.024	0.035	-10000	0	-0.4	3	3
SLC3A2	-0.003	0.084	-10000	0	-0.44	7	7
IRF4	-0.11	0.2	-10000	0	-0.4	143	143
PTGS2	-0.19	0.28	-10000	0	-0.77	45	45
CSF2	-0.25	0.32	-10000	0	-0.76	68	68
JunB/Fra1/NFAT1-c-4	-0.16	0.19	-10000	0	-0.79	14	14
IL4	-0.067	0.17	-10000	0	-0.74	14	14
IL5	-0.18	0.27	-10000	0	-0.78	32	32
IL2	-0.028	0.14	-10000	0	-0.66	1	1
IL3	-0.035	0.092	-10000	0	-0.69	6	6
RNF128	0.029	0.028	-10000	0	-0.49	1	1
NFATC1	-0.044	0.15	-10000	0	-0.81	11	11
CDK4	0.025	0.1	0.59	6	-10000	0	6
PTPRK	-0.003	0.084	-10000	0	-0.45	6	6
IL8	-0.29	0.32	-10000	0	-0.77	71	71
POU2F1	0.027	0.005	-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	0.026	0.02	-9999	-0.4	1	1
EGFR	0.024	0.021	-9999	-0.4	1	1
EGF/EGFR	-0.011	0.11	-9999	-0.21	94	94
EGF/EGFR dimer/SHC/GRB2/SOS1	0.018	0.11	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.001	0.11	-9999	-0.43	26	26
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.062	0.17	-9999	-0.4	89	89
EGF/EGFR dimer/SHC	-0.005	0.11	-9999	-0.24	79	79
mol:GDP	0.013	0.1	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.025	0.028	-9999	-0.4	2	2
GRB2/SOS1	0.04	0.007	-9999	-10000	0	0
HRAS/GTP	0.001	0.091	-9999	-10000	0	0
SHC1	0.027	0.004	-9999	-10000	0	0
HRAS/GDP	0.013	0.1	-9999	-10000	0	0
FRAP1	-0.042	0.07	-9999	-10000	0	0
EGF/EGFR dimer	-0.023	0.12	-9999	-0.28	81	81
SOS1	0.027	0.002	-9999	-10000	0	0
GRB2	0.027	0.004	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.018	0.083	-9999	-0.3	28	28

×

Thromboxane A2 receptor signaling

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
TGM2	0.013	0.038	-10000	0	-0.43	3	3
GNB1/GNG2	-0.053	0.05	-10000	0	-0.19	17	17
AKT1	-0.042	0.093	-10000	0	-0.29	32	32
EGF	-0.062	0.17	-10000	0	-0.4	89	89
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.071	0.08	-10000	0	-0.31	2	2
mol:Ca2+	-0.054	0.096	-10000	0	-0.29	31	31
LYN	-0.06	0.077	-10000	0	-10000	0	0
RhoA/GTP	-0.024	0.043	-10000	0	-0.14	6	6
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.059	0.1	-10000	0	-0.34	14	14
GNG2	0.009	0.081	-10000	0	-0.4	17	17
ARRB2	0.023	0.01	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.61	12	12
G beta5/gamma2	-0.061	0.067	-10000	0	-0.27	14	14
PRKCH	-0.057	0.1	-10000	0	-0.34	16	16
DNM1	0.024	0.046	0.36	1	-0.43	4	5
TXA2/TP beta/beta Arrestin3	-0.01	0.047	-10000	0	-0.62	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.18	0.21	-10000	0	-0.4	221	221
G12 family/GTP	-0.054	0.088	-10000	0	-0.3	14	14
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
ADRBK2	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.029	0.019	-10000	0	-0.23	1	1
mol:GDP	0.069	0.1	0.35	26	-10000	0	26
mol:NADP	0.018	0.066	0.36	1	-0.43	9	10
RAB11A	0.026	0.006	-10000	0	-10000	0	0
PRKG1	0.007	0.087	-10000	0	-0.4	20	20
mol:IP3	-0.067	0.12	-10000	0	-0.36	31	31
cell morphogenesis	0.029	0.019	-10000	0	-0.23	1	1
PLCB2	-0.091	0.15	-10000	0	-0.49	31	31
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.11	0.11	-10000	0	-0.3	74	74
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.042	0.073	-10000	0	-0.29	4	4
RHOA	0.027	0.004	-10000	0	-10000	0	0
PTGIR	0.026	0.022	-10000	0	-0.43	1	1
PRKCB1	-0.061	0.11	-10000	0	-0.36	19	19
GNAQ	0.026	0.02	-10000	0	-0.4	1	1
mol:L-citrulline	0.018	0.066	0.36	1	-0.43	9	10
TXA2/TXA2-R family	-0.086	0.14	-10000	0	-0.51	17	17
LCK	-0.074	0.082	-10000	0	-0.3	5	5
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.079	0.1	-10000	0	-0.24	3	3
TXA2-R family/G12 family/GDP/G beta/gamma	-0.032	0.12	-10000	0	-0.5	24	24
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.072	0.1	-10000	0	-0.24	2	2
MAPK14	-0.041	0.07	-10000	0	-0.23	12	12
TGM2/GTP	-0.076	0.12	-10000	0	-0.42	18	18
MAPK11	-0.041	0.071	-10000	0	-0.24	12	12
ARHGEF1	-0.035	0.055	-10000	0	-0.18	11	11
GNAI2	0.027	0.004	-10000	0	-10000	0	0
JNK cascade	-0.066	0.11	-10000	0	-0.37	17	17
RAB11/GDP	0.027	0.006	-10000	0	-10000	0	0
ICAM1	-0.044	0.082	-10000	0	-0.28	13	13
cAMP biosynthetic process	-0.07	0.11	-10000	0	-0.35	28	28
Gq family/GTP/EBP50	0.016	0.049	0.24	4	-0.32	5	9
actin cytoskeleton reorganization	0.029	0.019	-10000	0	-0.23	1	1
SRC	-0.041	0.069	-10000	0	-10000	0	0
GNB5	0.026	0.006	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
EGF/EGFR	-0.065	0.1	0.17	5	-0.28	26	31
VCAM1	-0.05	0.091	-10000	0	-0.38	12	12
TP beta/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.61	12	12
platelet activation	-0.054	0.094	-10000	0	-0.31	14	14
PGI2/IP	0.019	0.015	-10000	0	-0.3	1	1
PRKACA	-0.096	0.11	-10000	0	-0.21	214	214
Gq family/GDP/G beta5/gamma2	-0.033	0.11	-10000	0	-0.56	11	11
TXA2/TP beta/beta Arrestin2	-0.027	0.063	-10000	0	-0.25	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.092	0.1	-10000	0	-0.2	210	210
mol:DAG	-0.068	0.12	-10000	0	-0.39	22	22
EGFR	0.024	0.021	-10000	0	-0.4	1	1
TXA2/TP alpha	-0.09	0.15	-10000	0	-0.47	29	29
Gq family/GTP	0.01	0.054	0.3	3	-0.24	10	13
YES1	-0.065	0.078	-10000	0	-10000	0	0
GNAI2/GTP	-0.071	0.094	-10000	0	-0.23	2	2
PGD2/DP	-0.13	0.15	-10000	0	-0.28	221	221
SLC9A3R1	0.027	0.004	-10000	0	-10000	0	0
FYN	-0.071	0.078	-10000	0	-10000	0	0
mol:NO	0.018	0.066	0.36	1	-0.43	9	10
GNA15	0.022	0.048	-10000	0	-0.43	5	5
PGK/cGMP	0.017	0.069	0.23	1	-0.25	27	28
RhoA/GDP	0.028	0.004	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.043	0.1	-10000	0	-0.35	7	7
NOS3	0.018	0.066	0.36	1	-0.43	9	10
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.057	0.1	-10000	0	-0.34	15	15
PRKCB	-0.079	0.12	-10000	0	-0.39	26	26
PRKCE	-0.054	0.1	-10000	0	-0.34	15	15
PRKCD	-0.059	0.1	-10000	0	-0.37	15	15
PRKCG	-0.084	0.13	-10000	0	-0.4	20	20
muscle contraction	-0.083	0.14	-10000	0	-0.47	19	19
PRKCZ	-0.06	0.099	-10000	0	-0.34	14	14
ARR3	-0.008	0.034	-10000	0	-0.43	2	2
TXA2/TP beta	-0.073	0.1	-10000	0	-0.24	3	3
PRKCQ	-0.056	0.1	-10000	0	-0.34	17	17
MAPKKK cascade	-0.079	0.13	-10000	0	-0.43	26	26
SELE	-0.058	0.096	-10000	0	-0.29	17	17
TP beta/GNAI2/GDP/G beta/gamma	-0.073	0.12	-10000	0	-0.34	12	12
ROCK1	0.022	0.022	-10000	0	-0.4	1	1
GNA14	0.025	0.028	-10000	0	-0.4	2	2
chemotaxis	-0.087	0.15	-10000	0	-0.58	14	14
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.028	-10000	0	-0.4	2	2
Rac1/GTP	0.018	0.006	-10000	0	-10000	0	0

×

Arf6 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
CENTA1/KIF3B	0.026	0.028	-10000	0	-0.44	1	1
ARNO/beta Arrestin1-2	0.002	0.094	-10000	0	-0.8	2	2
EGFR	0.024	0.021	-10000	0	-0.4	1	1
EPHA2	0.025	0.022	-10000	0	-0.43	1	1
USP6	0.022	0.024	-10000	0	-0.43	1	1
IQSEC1	0.027	0.003	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.023	0.12	-10000	0	-0.28	81	81
ARRB2	0.008	0.004	-10000	0	-10000	0	0
mol:GTP	0.005	0.041	0.12	5	-0.26	2	7
ARRB1	0.026	0.02	-10000	0	-0.4	1	1
FBXO8	0.025	0.021	-10000	0	-0.4	1	1
TSHR	0.007	0.054	-10000	0	-0.4	7	7
EGF	-0.062	0.17	-10000	0	-0.4	89	89
somatostatin receptor activity	0	0	0.001	22	-0.001	24	46
ARAP2	0.026	0.02	-10000	0	-0.4	1	1
mol:GDP	-0.037	0.11	0.19	8	-0.27	46	54
mol:PI-3-4-5-P3	0	0	0.001	11	-0.001	8	19
ITGA2B	0.005	0.089	-10000	0	-0.43	18	18
ARF6	0.025	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.03	-10000	0	-0.22	2	2
ADAP1	0.024	0.021	-10000	0	-0.4	1	1
KIF13B	0.02	0.023	-10000	0	-0.4	1	1
HGF/MET	0.029	0.056	-10000	0	-0.29	13	13
PXN	0.027	0.002	-10000	0	-10000	0	0
ARF6/GTP	-0.025	0.11	0.22	20	-0.28	25	45
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.005	0.11	-10000	0	-0.24	81	81
ADRB2	-0.039	0.15	-10000	0	-0.4	69	69
receptor agonist activity	0	0	0	6	0	20	26
actin filament binding	0	0	0	22	-0.001	25	47
SRC	0.017	0.013	-10000	0	-10000	0	0
ITGB3	0.022	0.044	-10000	0	-0.4	5	5
GNAQ	0.026	0.02	-10000	0	-0.4	1	1
EFA6/PI-4-5-P2	0	0.001	0.001	28	-0.001	13	41
ARF6/GDP	-0.05	0.17	0.22	1	-0.46	44	45
ARF6/GDP/GULP/ACAP1	-0.026	0.12	0.23	2	-0.33	26	28
alphaIIb/beta3 Integrin/paxillin/GIT1	0.052	0.066	-10000	0	-0.23	22	22
ACAP1	0.011	0.068	-10000	0	-0.4	12	12
ACAP2	0.026	0.02	-10000	0	-0.4	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	0.06	-10000	0	-0.4	9	9
CYTH3	0.006	0.002	-10000	0	-10000	0	0
CYTH2	0.015	0.068	-10000	0	-1	2	2
NCK1	0.027	0.002	-10000	0	-10000	0	0
fibronectin binding	0	0	0	30	0	14	44
endosomal lumen acidification	0	0	0	34	-0.001	12	46
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.007	0.091	-10000	0	-0.4	22	22
GNAQ/ARNO	0.03	0.065	-10000	0	-0.92	2	2
mol:Phosphatidic acid	0	0	0	5	-10000	0	5
PIP3-E	0	0	0	8	0	5	13
MET	0.023	0.046	0.36	1	-0.43	4	5
GNA14	0.025	0.028	-10000	0	-0.4	2	2
GNA15	0.022	0.048	-10000	0	-0.43	5	5
GIT1	0.026	0.02	-10000	0	-0.4	1	1
mol:PI-4-5-P2	0	0	0.001	24	-0.001	19	43
GNA11	0.025	0.028	-10000	0	-0.4	2	2
LHCGR	-0.012	0.015	-10000	0	-10000	0	0
AGTR1	-0.12	0.2	-10000	0	-0.4	153	153
desensitization of G-protein coupled receptor protein signaling pathway	0.007	0.026	-10000	0	-10000	0	0
IPCEF1/ARNO	-0.001	0.097	-10000	0	-0.85	2	2
alphaIIb/beta3 Integrin	0.022	0.075	-10000	0	-0.3	23	23

×

Glucocorticoid receptor regulatory network

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
PCK2	0.056	0.061	-10000	0	-10000	0	0
SMARCC2	0.025	0.019	-10000	0	-10000	0	0
SMARCC1	0.024	0.019	-10000	0	-10000	0	0
TBX21	-0.1	0.18	0.32	1	-0.66	33	34
SUMO2	0.027	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.032	0.021	-10000	0	-0.42	1	1
FKBP4	0.027	0.016	0.36	1	-10000	0	1
FKBP5	0.026	0.02	-10000	0	-0.4	1	1
GR alpha/HSP90/FKBP51/HSP90	0.087	0.1	0.29	18	-0.25	16	34
PRL	-0.043	0.091	-10000	0	-0.54	1	1
cortisol/GR alpha (dimer)/TIF2	0.16	0.18	0.51	46	-0.39	3	49
RELA	-0.043	0.07	-10000	0	-0.23	1	1
FGG	0.08	0.18	0.44	22	-0.4	19	41
GR beta/TIF2	0.076	0.11	0.29	20	-0.3	16	36
IFNG	-0.18	0.16	-10000	0	-0.62	23	23
apoptosis	0	0.15	0.48	14	-0.5	6	20
CREB1	0.026	0.025	-10000	0	-10000	0	0
histone acetylation	-0.043	0.1	0.33	6	-0.35	17	23
BGLAP	-0.045	0.089	-10000	0	-0.41	3	3
GR/PKAc	0.063	0.14	0.3	12	-0.34	18	30
NF kappa B1 p50/RelA	-0.07	0.12	-10000	0	-0.3	25	25
SMARCD1	0.024	0.02	-10000	0	-10000	0	0
MDM2	0.057	0.058	0.22	22	-0.26	1	23
GATA3	0.023	0.049	-10000	0	-0.4	5	5
AKT1	0.021	0.006	-10000	0	-10000	0	0
CSF2	-0.11	0.12	-10000	0	-0.41	12	12
GSK3B	0.028	0.007	-10000	0	-10000	0	0
NR1I3	0.003	0.16	0.47	13	-0.7	5	18
CSN2	0.073	0.12	0.36	19	-0.31	5	24
BRG1/BAF155/BAF170/BAF60A	0.061	0.057	-10000	0	-0.27	4	4
NFATC1	0.019	0.036	-10000	0	-0.4	3	3
POU2F1	0.026	0.019	-10000	0	-10000	0	0
CDKN1A	-0.013	0.11	-10000	0	-1.4	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.007	-10000	0	-10000	0	0
SFN	0.023	0.029	-10000	0	-0.4	2	2
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.092	0.1	0.3	14	-0.26	8	22
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.001	0.14	0.44	12	-0.59	3	15
JUN	-0.18	0.12	-10000	0	-0.43	33	33
IL4	-0.053	0.084	-10000	0	-0.49	2	2
CDK5R1	0.026	0.022	-10000	0	-0.42	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.22	0.15	-10000	0	-0.4	121	121
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.098	0.1	0.3	16	-0.26	8	24
cortisol/GR alpha (monomer)	0.19	0.21	0.58	52	-0.41	4	56
NCOA2	0.023	0.022	-10000	0	-0.4	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.069	0.05	-10000	0	-0.44	3	3
AP-1/NFAT1-c-4	-0.27	0.16	-10000	0	-0.55	62	62
AFP	-0.13	0.1	-10000	0	-0.49	1	1
SUV420H1	0.027	0.004	-10000	0	-10000	0	0
IRF1	0.094	0.1	0.39	11	-0.37	1	12
TP53	0.033	0.029	-10000	0	-0.48	1	1
PPP5C	0.027	0.003	-10000	0	-10000	0	0
KRT17	-0.31	0.16	-10000	0	-0.53	88	88
KRT14	-0.083	0.21	-10000	0	-1.1	11	11
TBP	0.033	0.008	-10000	0	-10000	0	0
CREBBP	0.033	0.075	0.32	9	-0.25	17	26
HDAC1	0.025	0.008	-10000	0	-10000	0	0
HDAC2	0.035	0.013	-10000	0	-10000	0	0
AP-1	-0.27	0.16	-10000	0	-0.56	63	63
MAPK14	0.028	0.007	-10000	0	-10000	0	0
MAPK10	-0.03	0.14	-10000	0	-0.39	61	61
MAPK11	0.024	0.032	-10000	0	-0.43	2	2
KRT5	-0.2	0.17	-10000	0	-0.53	61	61
interleukin-1 receptor activity	0.008	0.011	-10000	0	-10000	0	0
NCOA1	0.029	0.001	-10000	0	-10000	0	0
STAT1	0.032	0.021	-10000	0	-0.42	1	1
CGA	-0.059	0.096	-10000	0	-0.41	5	5
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.078	0.14	0.33	28	-0.42	10	38
MAPK3	0.027	0.021	-10000	0	-0.4	1	1
MAPK1	0.027	0.009	-10000	0	-10000	0	0
ICAM1	-0.1	0.14	-10000	0	-0.46	19	19
NFKB1	-0.042	0.07	-10000	0	-0.23	2	2
MAPK8	-0.13	0.11	-10000	0	-0.39	29	29
MAPK9	0.028	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.001	0.16	0.48	14	-0.51	7	21
BAX	-0.007	0.075	-10000	0	-10000	0	0
POMC	-0.1	0.26	0.44	1	-1.3	17	18
EP300	0.032	0.075	0.32	9	-0.25	17	26
cortisol/GR alpha (dimer)/p53	0.17	0.19	0.53	40	-0.43	1	41
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.058	0.26	14	-0.23	1	15
SGK1	-0.005	0.28	-10000	0	-1.2	22	22
IL13	-0.14	0.12	-10000	0	-0.53	10	10
IL6	-0.13	0.19	0.34	1	-0.48	77	78
PRKACG	-0.005	0.029	-10000	0	-0.43	1	1
IL5	-0.12	0.11	-10000	0	-0.61	3	3
IL2	-0.18	0.14	-10000	0	-0.56	18	18
CDK5	0.027	0.006	-10000	0	-10000	0	0
PRKACB	-0.026	0.14	-10000	0	-0.4	56	56
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
IL8	-0.21	0.2	-10000	0	-0.54	44	44
CDK5R1/CDK5	0.039	0.02	-10000	0	-0.3	1	1
NF kappa B1 p50/RelA/PKAc	-0.064	0.12	-10000	0	-0.34	15	15
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.18	0.49	54	-0.4	1	55
SMARCA4	0.024	0.019	-10000	0	-10000	0	0
chromatin remodeling	0.08	0.15	0.35	24	-0.49	16	40
NF kappa B1 p50/RelA/Cbp	-0.018	0.13	0.36	5	-0.38	8	13
JUN (dimer)	-0.18	0.12	-10000	0	-0.43	33	33
YWHAH	0.026	0.006	-10000	0	-10000	0	0
VIPR1	-0.099	0.18	-10000	0	-0.76	27	27
NR3C1	0.094	0.16	0.38	35	-0.38	23	58
NR4A1	0.004	0.12	-10000	0	-0.5	23	23
TIF2/SUV420H1	0.034	0.021	-10000	0	-0.28	1	1
MAPKKK cascade	0	0.15	0.48	14	-0.5	6	20
cortisol/GR alpha (dimer)/Src-1	0.19	0.18	0.5	55	-0.39	2	57
PBX1	0.016	0.068	-10000	0	-0.4	11	11
POU1F1	0.002	0.036	-10000	0	-0.51	1	1
SELE	-0.13	0.18	-10000	0	-0.47	65	65
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.08	0.16	0.35	24	-0.49	16	40
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.18	0.49	54	-0.4	1	55
mol:cortisol	0.094	0.11	0.32	51	-10000	0	51
MMP1	-0.22	0.16	-10000	0	-0.84	7	7

×

Syndecan-4-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
PTK2	0.016	0.077	-10000	0	-0.38	7	7
Syndecan-4/Syndesmos	0.034	0.13	0.31	4	-0.5	3	7
positive regulation of JNK cascade	0.009	0.15	0.3	4	-0.56	3	7
Syndecan-4/ADAM12	-0.069	0.18	-10000	0	-0.41	30	30
CCL5	0.009	0.085	-10000	0	-0.4	19	19
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
DNM2	0.027	0.003	-10000	0	-10000	0	0
ITGA5	0.024	0.037	-10000	0	-0.43	3	3
SDCBP	0.023	0.022	-10000	0	-0.4	1	1
PLG	-0.089	0.17	-10000	0	-0.45	83	83
ADAM12	-0.25	0.22	-10000	0	-0.43	271	271
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.027	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.041	0.049	-10000	0	-0.16	3	3
Syndecan-4/Laminin alpha1	-0.013	0.13	0.31	4	-0.42	8	12
Syndecan-4/CXCL12/CXCR4	0.01	0.15	0.31	4	-0.59	3	7
Syndecan-4/Laminin alpha3	0.021	0.12	0.31	4	-0.5	3	7
MDK	0.023	0.043	-10000	0	-0.43	4	4
Syndecan-4/FZD7	0.036	0.13	0.31	4	-0.5	3	7
Syndecan-4/Midkine	0.033	0.13	0.31	4	-0.5	3	7
FZD7	0.027	0	-10000	0	-10000	0	0
Syndecan-4/FGFR1/FGF	0.013	0.13	0.3	2	-0.48	3	5
THBS1	0.025	0.022	-10000	0	-0.43	1	1
integrin-mediated signaling pathway	0.03	0.13	0.31	4	-0.47	5	9
positive regulation of MAPKKK cascade	0.009	0.15	0.3	4	-0.56	3	7
Syndecan-4/TACI	-0.039	0.14	0.31	2	-0.49	7	9
CXCR4	0.027	0.003	-10000	0	-10000	0	0
cell adhesion	0.009	0.053	0.2	13	-0.23	7	20
Syndecan-4/Dynamin	0.035	0.13	0.31	4	-0.5	3	7
Syndecan-4/TSP1	0.034	0.13	0.31	4	-0.47	4	8
Syndecan-4/GIPC	0.034	0.13	0.31	4	-0.5	3	7
Syndecan-4/RANTES	0.027	0.13	0.31	4	-0.5	3	7
ITGB1	0.027	0.002	-10000	0	-10000	0	0
LAMA1	-0.057	0.16	-10000	0	-0.4	84	84
LAMA3	0.019	0.036	-10000	0	-0.41	3	3
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.024	0.14	0.77	14	-10000	0	14
Syndecan-4/alpha-Actinin	0.031	0.13	0.31	4	-0.5	3	7
TFPI	0.025	0.035	-10000	0	-0.4	3	3
F2	-0.11	0.21	0.4	1	-0.41	144	145
alpha5/beta1 Integrin	0.038	0.028	-10000	0	-0.3	3	3
positive regulation of cell adhesion	-0.015	0.13	0.3	4	-0.45	5	9
ACTN1	0.026	0.007	-10000	0	-10000	0	0
TNC	0.015	0.071	-10000	0	-0.41	12	12
Syndecan-4/CXCL12	0.004	0.15	0.31	4	-0.61	3	7
FGF6	-0.017	0.027	0.36	1	-0.43	1	2
RHOA	0.027	0.004	-10000	0	-10000	0	0
CXCL12	-0.048	0.16	-10000	0	-0.4	80	80
TNFRSF13B	-0.12	0.19	-10000	0	-0.4	152	152
FGF2	-0.002	0.1	-10000	0	-0.4	30	30
FGFR1	0.021	0.035	-10000	0	-0.4	3	3
Syndecan-4/PI-4-5-P2	-0.011	0.096	0.29	4	-0.5	3	7
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.014	0.11	-10000	0	-0.42	28	28
cell migration	-0.021	0.02	-10000	0	-10000	0	0
PRKCD	0.013	0.024	-10000	0	-10000	0	0
vasculogenesis	0.034	0.13	0.31	4	-0.45	4	8
SDC4	-0.008	0.1	0.32	4	-0.53	3	7
Syndecan-4/Tenascin C	0.03	0.14	0.31	4	-0.48	5	9
Syndecan-4/PI-4-5-P2/PKC alpha	-0.033	0.038	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.026	0.12	0.31	3	-0.5	3	6
MMP9	-0.004	0.12	0.37	11	-0.42	27	38
Rac1/GTP	0.009	0.054	0.2	13	-0.23	7	20
cytoskeleton organization	0.034	0.13	0.31	4	-0.48	3	7
GIPC1	0.026	0.02	-10000	0	-0.4	1	1
Syndecan-4/TFPI	0.034	0.13	0.31	4	-0.5	3	7

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.002	-9999	-10000	0	0
ITGB7	0.01	0.083	-9999	-0.4	18	18
ITGA4	0.01	0.083	-9999	-0.4	18	18
alpha4/beta7 Integrin	0.016	0.092	-9999	-0.31	32	32
alpha4/beta1 Integrin	0.028	0.063	-9999	-0.28	18	18

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.048	-10000	0	-0.43	5	5
alphaV beta3 Integrin	0.036	0.034	-10000	0	-0.28	5	5
PTK2	0.016	0.067	-10000	0	-0.34	9	9
positive regulation of JNK cascade	0.027	0.069	-10000	0	-0.29	6	6
CDC42/GDP	0.055	0.097	-10000	0	-0.36	7	7
Rac1/GDP	0.05	0.095	-10000	0	-0.36	7	7
RAP1B	0.027	0.002	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.046	0.086	-10000	0	-0.35	6	6
nectin-3/I-afadin	0.031	0.052	-10000	0	-0.28	12	12
RAPGEF1	0.032	0.091	0.28	2	-0.37	10	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.084	-10000	0	-0.4	12	12
PDGFB-D/PDGFRB	0.022	0.048	-10000	0	-0.43	5	5
TLN1	-0.001	0.029	-10000	0	-0.27	3	3
Rap1/GTP	0.021	0.066	-10000	0	-0.3	5	5
IQGAP1	0.026	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	0.031	0.052	-10000	0	-0.28	12	12
PVR	0.027	0.003	-10000	0	-10000	0	0
Necl-5(dimer)	0.027	0.003	-10000	0	-10000	0	0
mol:GDP	0.048	0.11	-10000	0	-0.41	12	12
MLLT4	0.027	0.004	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
PI3K	0.066	0.057	-10000	0	-10000	0	0
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	0.026	0.079	-10000	0	-0.28	9	9
PVRL1	0.027	0.004	-10000	0	-10000	0	0
PVRL3	0.016	0.068	-10000	0	-0.4	12	12
PVRL2	0.027	0.003	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
CDH1	0.027	0.002	-10000	0	-10000	0	0
CLDN1	-0.39	0.13	0.36	1	-0.43	410	411
JAM-A/CLDN1	-0.21	0.094	-10000	0	-0.24	389	389
SRC	0.007	0.094	-10000	0	-0.41	18	18
ITGB3	0.022	0.044	-10000	0	-0.4	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.039	0.008	-10000	0	-10000	0	0
FARP2	0.05	0.11	-10000	0	-0.46	6	6
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)	0.046	0.048	-10000	0	-0.24	12	12
nectin-1/I-afadin	0.039	0.008	-10000	0	-10000	0	0
nectin-2/I-afadin	0.039	0.007	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.032	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.046	0.048	-10000	0	-0.24	12	12
CDC42/GTP/IQGAP1/filamentous actin	0.033	0.017	-10000	0	-0.23	1	1
F11R	0.027	0.004	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.027	0.069	-10000	0	-0.29	6	6
alphaV/beta3 Integrin/Talin	0.008	0.07	-10000	0	-0.29	3	3
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.007	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.039	0.007	-10000	0	-10000	0	0
PIP5K1C	0.002	0.032	-10000	0	-0.29	3	3
VAV2	0.041	0.12	-10000	0	-0.43	12	12
RAP1/GDP	0.058	0.091	-10000	0	-0.34	6	6
ITGAV	0.027	0.002	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.046	0.048	-10000	0	-0.24	12	12
nectin-3(dimer)/I-afadin/I-afadin	0.031	0.052	-10000	0	-0.28	12	12
Rac1/GTP	0.034	0.096	-10000	0	-0.34	8	8
PTPRM	0.006	0.039	-10000	0	-0.36	3	3
E-cadherin/beta catenin/alpha catenin	0.076	0.022	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.025	0.021	-10000	0	-0.4	1	1

×

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	0.039	0.02	0.26	1	-0.28	1	2
alphaV beta3 Integrin	0.031	0.08	-10000	0	-0.25	33	33
PTK2	0.028	0.11	0.3	12	-0.37	4	16
IGF1R	0.026	0.006	-10000	0	-10000	0	0
PI4KB	0.027	0.004	-10000	0	-10000	0	0
MFGE8	0.026	0.005	-10000	0	-10000	0	0
SRC	0.017	0.013	-10000	0	-10000	0	0
CDKN1B	0.011	0.043	-10000	0	-0.4	1	1
VEGFA	0.028	0.016	0.36	1	-10000	0	1
ILK	0.011	0.039	-10000	0	-0.21	1	1
ROCK1	0.022	0.022	-10000	0	-0.4	1	1
AKT1	0.005	0.033	-10000	0	-10000	0	0
PTK2B	0.01	0.032	-10000	0	-10000	0	0
alphaV/beta3 Integrin/JAM-A	0.029	0.082	-10000	0	-0.4	2	2
CBL	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.044	0.038	-10000	0	-0.24	7	7
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.002	0.12	-10000	0	-0.21	102	102
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.017	0.04	0.15	1	-0.36	3	4
alphaV/beta3 Integrin/Syndecan-1	0.051	0.032	-10000	0	-0.24	5	5
PI4KA	0.026	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.032	0.15	-10000	0	-0.39	30	30
PI4 Kinase	0.038	0.01	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.1	0.16	-10000	0	-0.26	220	220
RPS6KB1	-0.077	0.11	-10000	0	-0.37	29	29
TLN1	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.045	0.15	-10000	0	-0.51	39	39
GPR124	0.022	0.022	-10000	0	-0.4	1	1
MAPK1	-0.045	0.16	-10000	0	-0.5	40	40
PXN	0.027	0.002	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.021	0.092	-10000	0	-0.24	50	50
cell adhesion	0.04	0.037	-10000	0	-0.24	5	5
ANGPTL3	-0.003	0.036	-10000	0	-0.43	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.033	0.027	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
TGFBR2	0.027	0.003	-10000	0	-10000	0	0
ITGB3	0.022	0.044	-10000	0	-0.4	5	5
IGF1	-0.079	0.18	-10000	0	-0.4	112	112
RAC1	0.025	0.008	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.042	0.037	-10000	0	-0.23	6	6
apoptosis	0.027	0.002	-10000	0	-10000	0	0
CD47	0.027	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.05	0.032	-10000	0	-0.24	5	5
VCL	0.027	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.002	0.12	-10000	0	-0.25	81	81
CSF1	0.026	0.021	-10000	0	-0.4	1	1
PIK3C2A	0.01	0.043	-10000	0	-0.3	2	2
PI4 Kinase/Pyk2	0.012	0.069	-10000	0	-0.36	2	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.064	0.036	0.26	1	-10000	0	1
FAK1/Vinculin	0.041	0.1	0.24	25	-0.32	3	28
alphaV beta3/Integrin/ppsTEM5	0.043	0.038	-10000	0	-0.23	6	6
RHOA	0.027	0.004	-10000	0	-10000	0	0
VTN	0.006	0.079	-10000	0	-0.43	14	14
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
FGF2	-0.002	0.1	-10000	0	-0.4	30	30
F11R	-0.006	0.072	-10000	0	-0.28	29	29
alphaV/beta3 Integrin/Lactadherin	0.049	0.033	-10000	0	-0.23	5	5
alphaV/beta3 Integrin/TGFBR2	0.051	0.032	-10000	0	-0.24	5	5
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.065	0.025	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.047	0.03	-10000	0	-0.21	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0	0.11	-10000	0	-0.42	28	28
alphaV/beta3 Integrin/Pyk2	0.037	0.039	-10000	0	-10000	0	0
SDC1	0.027	0.001	-10000	0	-10000	0	0
VAV3	-0.009	0.067	-10000	0	-10000	0	0
PTPN11	0.027	0.003	-10000	0	-10000	0	0
IRS1	0.027	0.002	-10000	0	-10000	0	0
FAK1/Paxillin	0.041	0.1	0.24	24	-0.32	3	27
cell migration	0.036	0.097	0.22	35	-0.29	3	38
ITGAV	0.027	0.002	-10000	0	-10000	0	0
PI3K	0.042	0.084	-10000	0	-0.37	2	2
SPP1	-0.19	0.23	-10000	0	-0.43	215	215
KDR	0.026	0.02	-10000	0	-0.4	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.027	0.002	-10000	0	-10000	0	0
COL4A3	-0.023	0.13	-10000	0	-0.4	45	45
angiogenesis	-0.04	0.16	-10000	0	-0.51	38	38
Rac1/GTP	0.004	0.064	-10000	0	-10000	0	0
EDIL3	-0.051	0.16	-10000	0	-0.4	83	83
cell proliferation	0.05	0.032	-10000	0	-0.24	5	5

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.017	0.1	-10000	0	-0.23	84	84
cell-cell adhesion	0.041	0.07	0.36	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	0.047	0.051	-10000	0	-10000	0	0
ITSN1	0.026	0.005	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.021	0.066	-10000	0	-0.26	24	24
Ephrin B1/EPHB1	-0.035	0.13	0.23	2	-0.26	112	114
HRAS/GDP	-0.027	0.1	-10000	0	-0.31	13	13
Ephrin B/EPHB1/GRB7	0.005	0.11	0.26	4	-0.32	2	6
Endophilin/SYNJ1	0.044	0.075	0.21	4	-10000	0	4
KRAS	0.027	0.003	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.009	0.088	0.26	1	-0.42	1	2
endothelial cell migration	0.043	0.027	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.033	0.044	0.36	8	-10000	0	8
PAK1	0.031	0.084	0.21	5	-10000	0	5
HRAS	0.026	0.02	-10000	0	-0.4	1	1
RRAS	0.047	0.077	0.21	6	-10000	0	6
DNM1	0.024	0.046	0.36	1	-0.43	4	5
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.013	0.1	-10000	0	-0.4	1	1
lamellipodium assembly	-0.041	0.07	-10000	0	-0.36	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.014	0.059	0.17	1	-10000	0	1
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
EPHB2	0.024	0.031	-10000	0	-0.43	2	2
EPHB3	0.003	0.1	-10000	0	-0.43	24	24
EPHB1	-0.085	0.2	0.36	2	-0.43	112	114
EPHB4	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	-0.016	0.089	-10000	0	-0.29	14	14
Ephrin B/EPHB2	0.037	0.044	-10000	0	-0.22	4	4
Ephrin B/EPHB3	0.026	0.07	-10000	0	-0.23	23	23
JNK cascade	-0.045	0.1	0.34	2	-0.38	3	5
Ephrin B/EPHB1	-0.005	0.1	0.24	1	-0.22	75	76
RAP1/GDP	-0.003	0.11	0.34	6	-10000	0	6
EFNB2	0.021	0.011	-10000	0	-10000	0	0
EFNB3	0.016	0.05	-10000	0	-0.41	6	6
EFNB1	0.027	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.009	0.1	0.24	2	-0.24	71	73
RAP1B	0.027	0.002	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.011	0.097	-10000	0	-0.34	3	3
Rap1/GTP	-0.019	0.083	-10000	0	-0.37	3	3
axon guidance	-0.017	0.1	-10000	0	-0.23	84	84
MAPK3	0.007	0.053	0.19	3	-10000	0	3
MAPK1	0.007	0.05	0.17	1	-10000	0	1
Rac1/GDP	-0.018	0.097	0.32	1	-0.28	2	3
actin cytoskeleton reorganization	-0.037	0.076	-10000	0	-0.28	3	3
CDC42/GDP	-0.008	0.11	0.31	9	-0.28	2	11
PI3K	0.047	0.029	-10000	0	-10000	0	0
EFNA5	-0.051	0.16	-10000	0	-0.4	82	82
Ephrin B2/EPHB4	0.028	0.016	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.017	0.027	-10000	0	-10000	0	0
CDC42	0.025	0.021	-10000	0	-0.4	1	1
RAS family/GTP	-0.023	0.083	-10000	0	-0.36	4	4
PTK2	0.09	0.21	0.58	66	-10000	0	66
MAP4K4	-0.045	0.11	0.34	2	-0.39	3	5
SRC	0.017	0.013	-10000	0	-10000	0	0
KALRN	0.026	0.02	-10000	0	-0.4	1	1
Intersectin/N-WASP	0.038	0.01	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.008	0.096	0.27	14	-10000	0	14
MAP2K1	0.01	0.054	0.16	1	-10000	0	1
WASL	0.027	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.011	0.13	-10000	0	-0.24	112	112
cell migration	0.028	0.082	0.21	31	-10000	0	31
NRAS	0.025	0.029	-10000	0	-0.4	2	2
SYNJ1	0.044	0.075	0.21	4	-10000	0	4
PXN	0.027	0.002	-10000	0	-10000	0	0
TF	0.009	0.1	0.19	23	-0.39	2	25
HRAS/GTP	-0.007	0.095	-10000	0	-0.38	3	3
Ephrin B1/EPHB1-2	-0.021	0.13	0.24	2	-0.24	112	114
cell adhesion mediated by integrin	-0.039	0.095	0.25	2	-0.21	96	98
RAC1	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.006	0.098	-10000	0	-0.4	3	3
RAC1-CDC42/GTP	-0.036	0.095	-10000	0	-0.38	12	12
RASA1	0.027	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.011	0.098	0.31	1	-10000	0	1
ruffle organization	-0.006	0.12	0.36	20	-0.37	3	23
NCK1	0.027	0.002	-10000	0	-10000	0	0
receptor internalization	0.028	0.081	0.19	24	-10000	0	24
Ephrin B/EPHB2/KALRN	0.047	0.053	-10000	0	-10000	0	0
ROCK1	0	0.055	0.18	1	-0.22	25	26
RAS family/GDP	-0.044	0.063	-10000	0	-0.28	1	1
Rac1/GTP	-0.025	0.082	-10000	0	-0.38	3	3
Ephrin B/EPHB1/Src/Paxillin	0.002	0.051	0.17	1	-10000	0	1

×

Regulation of Androgen receptor activity

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
HDAC1	0.009	0.011	-10000	0	-10000	0	0
SMARCC1	0.013	0.01	-10000	0	-10000	0	0
REL	0.029	0.008	-10000	0	-10000	0	0
HDAC7	-0.022	0.085	-10000	0	-0.38	4	4
JUN	0.025	0.006	-10000	0	-10000	0	0
EP300	0.026	0.006	-10000	0	-10000	0	0
KAT2B	0.01	0.081	-10000	0	-0.4	17	17
KAT5	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.001	0.035	-10000	0	-0.3	4	4
FOXO1	0.02	0.023	-10000	0	-0.4	1	1
T-DHT/AR	-0.004	0.1	-10000	0	-0.39	4	4
MAP2K6	0.015	0.045	-10000	0	-0.41	4	4
BRM/BAF57	0.027	0.032	-10000	0	-0.31	1	1
MAP2K4	0.015	0.02	-10000	0	-10000	0	0
SMARCA2	0.018	0.028	-10000	0	-0.41	1	1
PDE9A	-0.16	0.39	-10000	0	-0.97	80	80
NCOA2	0.023	0.022	-10000	0	-0.4	1	1
CEBPA	0.024	0.035	-10000	0	-0.39	3	3
EHMT2	0.026	0.017	0.36	1	-10000	0	1
cell proliferation	0.032	0.13	0.25	30	-0.36	5	35
NR0B1	-0.008	0.053	-10000	0	-0.43	6	6
EGR1	0.02	0.026	-10000	0	-0.4	1	1
RXRs/9cRA	-0.058	0.12	-10000	0	-0.22	167	167
AR/RACK1/Src	0.05	0.099	0.25	4	-0.35	1	5
AR/GR	-0.017	0.09	-10000	0	-0.29	20	20
GNB2L1	0.027	0.004	-10000	0	-10000	0	0
PKN1	0.027	0.004	-10000	0	-10000	0	0
RCHY1	0.027	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-10000	0	-0.012	1	1
MAPK8	0.003	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.006	0.063	-10000	0	-0.31	3	3
SRC	0.024	0.086	0.19	87	-0.26	3	90
NR3C1	-0.001	0.11	-10000	0	-0.4	30	30
KLK3	-0.22	0.42	-10000	0	-1.2	71	71
APPBP2	0.018	0.028	-10000	0	-0.39	1	1
TRIM24	0.019	0.019	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.005	0.058	0.2	2	-0.32	3	5
TMPRSS2	-0.017	0.13	-10000	0	-0.73	7	7
RXRG	-0.15	0.19	-10000	0	-0.4	168	168
mol:9cRA	-0.001	0.002	-10000	0	-10000	0	0
RXRA	0.026	0.02	-10000	0	-0.4	1	1
RXRB	0.027	0.003	-10000	0	-10000	0	0
CARM1	0.027	0.004	-10000	0	-10000	0	0
NR2C2	0.027	0.004	-10000	0	-10000	0	0
KLK2	0.022	0.088	0.24	1	-0.38	1	2
AR	-0.011	0.064	0.16	1	-0.26	24	25
SENP1	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
MDM2	0.03	0.023	-10000	0	-0.4	1	1
SRY	0.004	0.011	0.028	74	-10000	0	74
GATA2	0.017	0.065	-10000	0	-0.4	11	11
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	-0.14	0.22	0.36	3	-0.43	155	158
T-DHT/AR/RACK1/Src	0.058	0.1	0.26	7	-0.31	3	10
positive regulation of transcription	0.017	0.065	-10000	0	-0.4	11	11
DNAJA1	0.019	0.02	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.016	-10000	0	-0.29	1	1
NCOA1	0.025	0.019	-10000	0	-10000	0	0
SPDEF	-0.059	0.16	-10000	0	-0.4	86	86
T-DHT/AR/TIF2	-0.001	0.068	-10000	0	-0.28	7	7
T-DHT/AR/Hsp90	-0.006	0.055	0.2	1	-0.32	3	4
GSK3B	0.026	0.004	-10000	0	-10000	0	0
NR2C1	0.028	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.016	0.035	0.22	1	-0.27	3	4
SIRT1	0.027	0.005	-10000	0	-10000	0	0
ZMIZ2	0.029	0.014	-10000	0	-10000	0	0
POU2F1	0.015	0.052	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.015	0.061	0.19	2	-0.31	4	6
CREBBP	0.027	0.004	-10000	0	-10000	0	0
SMARCE1	0.019	0.019	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.037	0.1	-10000	0	-0.32	32	32
ACTA1	-0.054	0.1	-10000	0	-0.34	26	26
NUMA1	-0.036	0.11	-10000	0	-0.34	32	32
SPTAN1	-0.054	0.1	-10000	0	-0.34	25	25
LIMK1	-0.048	0.1	0.24	5	-0.34	23	28
BIRC3	0.019	0.057	-10000	0	-0.4	8	8
BIRC2	0.027	0.005	-10000	0	-10000	0	0
BAX	0.027	0.003	-10000	0	-10000	0	0
CASP10	-0.074	0.12	-10000	0	-0.27	112	112
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.027	0.002	-10000	0	-10000	0	0
PTK2	-0.036	0.11	-10000	0	-0.33	34	34
DIABLO	0.027	0.003	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.053	0.1	-10000	0	-0.33	25	25
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	-10000	0	-0.35	29	29
MADD	0.027	0.003	-10000	0	-10000	0	0
TFAP2A	0.001	0.082	-10000	0	-0.57	7	7
BID	-0.027	0.063	-10000	0	-0.22	19	19
MAP3K1	-0.02	0.076	-10000	0	-0.39	13	13
TRADD	0.027	0.002	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.011	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.054	0.1	-10000	0	-0.34	25	25
CASP9	0.026	0.007	-10000	0	-10000	0	0
DNA repair	0.008	0.041	0.2	2	-10000	0	2
neuron apoptosis	-0.015	0.16	-10000	0	-0.71	22	22
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.046	0.11	-10000	0	-0.34	31	31
APAF1	0.027	0.003	-10000	0	-10000	0	0
CASP6	-0.025	0.16	-10000	0	-0.88	14	14
TRAF2	0.026	0.02	-10000	0	-0.4	1	1
ICAD/CAD	-0.052	0.096	-10000	0	-0.32	25	25
CASP7	0.002	0.058	0.24	6	-0.26	9	15
KRT18	0.012	0.031	-10000	0	-10000	0	0
apoptosis	-0.05	0.12	0.35	1	-0.38	30	31
DFFA	-0.054	0.099	-10000	0	-0.34	25	25
DFFB	-0.053	0.1	0.19	2	-0.34	25	27
PARP1	-0.009	0.041	-10000	0	-0.2	2	2
actin filament polymerization	0.046	0.097	0.32	21	-0.25	2	23
TNF	0.025	0.029	-10000	0	-0.4	2	2
CYCS	-0.013	0.055	0.19	1	-0.17	14	15
SATB1	-0.029	0.15	-10000	0	-0.82	14	14
SLK	-0.054	0.1	0.34	1	-0.34	25	26
p15 BID/BAX	-0.017	0.069	-10000	0	-0.22	15	15
CASP2	0.022	0.045	0.21	12	-10000	0	12
JNK cascade	0.02	0.076	0.39	13	-10000	0	13
CASP3	-0.056	0.11	-10000	0	-0.35	26	26
LMNB2	0.011	0.1	0.28	1	-0.61	7	8
RIPK1	0.027	0.003	-10000	0	-10000	0	0
CASP4	0.027	0.004	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.063	0.04	-10000	0	-0.22	8	8
negative regulation of DNA binding	0.002	0.082	-10000	0	-0.57	7	7
stress fiber formation	-0.054	0.1	0.34	1	-0.33	25	26
GZMB	-0.071	0.15	-10000	0	-0.32	112	112
CASP1	0.014	0.014	-10000	0	-0.28	1	1
LMNB1	0.007	0.1	0.24	2	-0.38	17	19
APP	-0.016	0.17	-10000	0	-0.72	22	22
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	-10000	0	-0.38	31	31
LMNA	0.018	0.066	0.28	1	-0.32	2	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.023	0.033	-10000	0	-0.22	1	1
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.05	0.098	-10000	0	-0.33	25	25
APAF-1/Caspase 9	-0.022	0.15	-10000	0	-0.62	26	26
nuclear fragmentation during apoptosis	-0.036	0.11	-10000	0	-0.33	32	32
CFL2	-0.047	0.099	0.25	2	-0.32	21	23
GAS2	-0.089	0.14	0.19	1	-0.38	51	52
positive regulation of apoptosis	0.016	0.091	0.24	2	-0.38	15	17
PRF1	0.019	0.056	-10000	0	-0.4	8	8

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.038	0.1	0.22	26	-0.31	1	27
PDGFB-D/PDGFRB/SLAP	0.03	0.044	-10000	0	-0.3	7	7
PDGFB-D/PDGFRB/APS/CBL	0.048	0.045	0.26	1	-0.25	8	9
AKT1	0.054	0.093	0.27	10	-10000	0	10
mol:PI-4-5-P2	0.001	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.066	0.12	0.24	60	-0.38	1	61
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
FGR	0.007	0.12	0.34	1	-0.46	20	21
mol:Ca2+	0.061	0.11	0.24	59	-0.45	1	60
MYC	0.092	0.16	0.39	61	-10000	0	61
SHC1	0.027	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.062	0.075	-10000	0	-10000	0	0
LRP1/PDGFRB/PDGFB	0.048	0.043	-10000	0	-0.25	8	8
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	0.027	0.003	-10000	0	-10000	0	0
GO:0007205	0.061	0.11	0.24	57	-0.46	1	58
PTEN	0.026	0.006	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
GRB7	0.033	0.044	0.36	8	-10000	0	8
PDGFB-D/PDGFRB/SHP2	0.037	0.037	-10000	0	-0.3	5	5
PDGFB-D/PDGFRB/GRB10	0.034	0.035	-10000	0	-0.3	4	4
cell cycle arrest	0.03	0.044	-10000	0	-0.3	7	7
HRAS	0.026	0.02	-10000	0	-0.4	1	1
HIF1A	0.048	0.087	0.25	11	-10000	0	11
GAB1	0.044	0.12	0.24	17	-0.32	3	20
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.058	0.12	0.23	70	-0.3	1	71
PDGFB-D/PDGFRB	0.026	0.042	-10000	0	-0.26	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.037	0.037	-10000	0	-0.3	5	5
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.006	0.06	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.037	0.037	-10000	0	-0.3	5	5
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.061	0.11	0.24	57	-0.46	1	58
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.024	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.041	0.048	0.26	8	-0.3	5	13
SHB	0.027	0.004	-10000	0	-10000	0	0
BLK	-0.15	0.23	-10000	0	-0.47	148	148
PTPN2	0.024	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.037	0.037	-10000	0	-0.3	5	5
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
VAV2	0.053	0.13	0.26	70	-0.35	3	73
CBL	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.037	0.037	-10000	0	-0.3	5	5
LCK	0.016	0.11	0.34	1	-0.43	14	15
PDGFRB	0.024	0.048	-10000	0	-0.43	5	5
ACP1	0.027	0.002	-10000	0	-10000	0	0
HCK	0.004	0.08	-10000	0	-0.5	8	8
ABL1	0.037	0.13	0.23	62	-0.33	9	71
PDGFB-D/PDGFRB/CBL	0.033	0.12	0.33	1	-0.38	4	5
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	0.026	0.021	-10000	0	-0.43	1	1
cell proliferation	0.09	0.15	0.38	63	-10000	0	63
SLA	0.021	0.03	-10000	0	-0.4	2	2
actin cytoskeleton reorganization	0.084	0.086	0.34	3	-10000	0	3
SRC	0.011	0.041	-10000	0	-10000	0	0
PI3K	-0.003	0.026	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.053	0.043	0.25	7	-0.25	5	12
SH2B2	0.024	0.041	0.36	1	-0.43	3	4
PLCgamma1/SPHK1	0.067	0.13	0.25	59	-0.39	1	60
LYN	0.021	0.079	0.34	1	-0.56	3	4
LRP1	0.025	0.028	-10000	0	-0.4	2	2
SOS1	0.027	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	0.052	-10000	0	-10000	0	0
SPHK1	-0.002	0.12	-10000	0	-0.42	32	32
EDG1	0.003	0.004	-10000	0	-10000	0	0
mol:DAG	0.061	0.11	0.24	57	-0.46	1	58
PLCG1	0.061	0.12	0.24	57	-0.48	1	58
NHERF/PDGFRB	0.05	0.037	-10000	0	-0.25	6	6
YES1	-0.008	0.15	0.34	1	-0.49	32	33
cell migration	0.05	0.037	-10000	0	-0.25	6	6
SHC/Grb2/SOS1	0.038	0.05	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.02	-10000	0	-0.4	1	1
SLC9A3R1	0.027	0.004	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.061	0.04	-10000	0	-10000	0	0
FYN	0.02	0.081	0.34	1	-0.38	7	8
DOK1	0.056	0.084	0.19	4	-10000	0	4
HRAS/GTP	0.019	0.014	-10000	0	-0.28	1	1
PDGFB	0.025	0.022	-10000	0	-0.43	1	1
RAC1	0.069	0.14	0.34	48	-0.38	1	49
PRKCD	0.056	0.085	0.19	21	-10000	0	21
FER	0.056	0.085	0.18	75	-0.24	2	77
MAPKKK cascade	0.063	0.099	0.34	8	-10000	0	8
RASA1	0.056	0.085	0.19	58	-10000	0	58
NCK1	0.027	0.002	-10000	0	-10000	0	0
NCK2	0.027	0	-10000	0	-10000	0	0
p62DOK/Csk	0.064	0.074	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.037	0.037	-10000	0	-0.3	5	5
chemotaxis	0.037	0.12	0.23	63	-0.32	9	72
STAT1-3-5/STAT1-3-5	0.032	0.045	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.018	0.034	-10000	0	-0.3	5	5
PTPRJ	0.027	0.003	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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
NFATC2	0.007	0.062	-10000	0	-0.4	10	10
GNB1/GNG2	-0.021	0.11	-10000	0	-0.32	20	20
mol:DAG	-0.021	0.08	0.19	1	-0.32	11	12
PLCG1	-0.021	0.082	0.2	1	-0.33	11	12
YES1	-0.029	0.087	-10000	0	-0.29	23	23
FZD3	0.022	0.033	0.36	2	-0.43	1	3
FZD6	0.023	0.01	-10000	0	-10000	0	0
G protein	0.025	0.12	0.28	8	-0.33	12	20
MAP3K7	-0.029	0.075	-10000	0	-0.32	7	7
mol:Ca2+	-0.02	0.078	0.19	1	-0.31	11	12
mol:IP3	-0.021	0.08	0.19	1	-0.32	11	12
NLK	0	0.079	-10000	0	-0.74	5	5
GNB1	0.026	0.007	-10000	0	-10000	0	0
CAMK2A	-0.028	0.081	-10000	0	-0.32	11	11
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.025	0.097	0.17	1	-0.31	24	25
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
GNAS	-0.016	0.084	0.33	1	-0.32	15	16
GO:0007205	-0.023	0.078	0.19	1	-0.31	11	12
WNT6	-0.002	0.1	-10000	0	-0.41	25	25
WNT4	0.007	0.088	-10000	0	-0.4	20	20
NFAT1/CK1 alpha	-0.012	0.089	-10000	0	-0.4	7	7
GNG2	0.009	0.081	-10000	0	-0.4	17	17
WNT5A	0.022	0.048	-10000	0	-0.43	5	5
WNT11	-0.065	0.18	-10000	0	-0.42	92	92
CDC42	-0.029	0.084	-10000	0	-0.33	11	11

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.014	-10000	0	-0.28	1	1
MAP4K4	0.018	0.037	-10000	0	-10000	0	0
BAG4	0.023	0.01	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.015	0.068	-10000	0	-0.19	47	47
NFKBIA	0.025	0.007	-10000	0	-10000	0	0
BIRC3	0.019	0.057	-10000	0	-0.4	8	8
BAX	-0.003	0.039	-10000	0	-0.34	3	3
RIPK1	0.027	0.003	-10000	0	-10000	0	0
AKT1	-0.002	0.012	-10000	0	-10000	0	0
BAD	-0.03	0.061	-10000	0	-0.19	48	48
SMPD1	0.021	0.047	0.15	5	-0.23	5	10
RB1	0.013	0.089	0.19	68	-0.19	24	92
FADD/Caspase 8	0.025	0.037	0.2	1	-10000	0	1
MAP2K4	-0.028	0.058	-10000	0	-0.22	11	11
NSMAF	0.024	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.025	0.064	0.18	9	-0.21	14	23
EGF	-0.062	0.17	-10000	0	-0.4	89	89
mol:ceramide	-0.03	0.065	-10000	0	-0.2	48	48
MADD	0.027	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	0.012	0.089	0.18	70	-0.19	24	94
cell proliferation	-0.043	0.097	-10000	0	-0.31	8	8
BID	-0.001	0.14	-10000	0	-0.6	20	20
MAP3K1	-0.03	0.062	-10000	0	-0.19	49	49
EIF2A	-0.031	0.058	0.17	3	-0.22	10	13
TRADD	0.027	0.002	-10000	0	-10000	0	0
CRADD	0.027	0.003	-10000	0	-10000	0	0
MAPK3	-0.021	0.062	0.18	9	-0.22	8	17
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.026	0.064	0.18	7	-0.22	9	16
Cathepsin D/ceramide	-0.015	0.069	-10000	0	-0.19	48	48
FADD	0.019	0.037	0.21	1	-10000	0	1
KSR1	-0.024	0.067	0.19	8	-0.19	45	53
MAPK8	-0.025	0.067	-10000	0	-0.22	12	12
PRKRA	-0.03	0.061	-10000	0	-0.19	48	48
PDGFA	0.025	0.008	-10000	0	-10000	0	0
TRAF2	0.026	0.02	-10000	0	-0.4	1	1
IGF1	-0.079	0.18	-10000	0	-0.4	112	112
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.03	0.065	-10000	0	-0.2	48	48
CTSD	0.026	0.02	-10000	0	-0.4	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	-0.045	0.1	-10000	0	-0.34	8	8
PRKCD	0.027	0.004	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-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	0.027	0.003	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.03	-10000	0	-0.24	1	1
TNFR1A/BAG4/TNF-alpha	0.045	0.029	-10000	0	-0.24	2	2
mol:Sphingosine-1-phosphate	0.012	0.014	-10000	0	-0.28	1	1
MAP2K1	-0.025	0.062	0.18	9	-0.22	8	17
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
CYCS	0.017	0.05	0.16	7	-10000	0	7
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.034	0.015	-10000	0	-10000	0	0
EIF2AK2	-0.031	0.06	0.18	1	-0.19	37	38
TNF-alpha/TNFR1A/FAN	0.046	0.028	-10000	0	-0.24	2	2
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.029	0.049	-10000	0	-0.28	3	3
MAP2K2	-0.025	0.062	0.17	10	-0.22	9	19
SMPD3	0.02	0.059	0.19	1	-0.29	11	12
TNF	0.025	0.029	-10000	0	-0.4	2	2
PKC zeta/PAR4	0.038	0.011	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.028	0.082	0.19	69	-10000	0	69
NF kappa B1/RelA/I kappa B alpha	0.069	0.03	-10000	0	-10000	0	0
AIFM1	0.01	0.059	0.15	7	-0.15	4	11
BCL2	0.012	0.059	-10000	0	-0.4	9	9

×

Signaling events mediated by HDAC Class III

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
EP300	0.026	0.006	-10000	0	-10000	0	0
HDAC4	0.027	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	-0.01	0.033	0.3	4	-0.27	1	5
CDKN1A	-0.009	0.036	-10000	0	-0.53	2	2
KAT2B	0.011	0.081	-10000	0	-0.4	17	17
BAX	0.027	0.003	-10000	0	-10000	0	0
FOXO3	-0.005	0.003	-10000	0	-10000	0	0
FOXO1	0.02	0.023	-10000	0	-0.4	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	-0.15	0.2	-10000	0	-0.4	173	173
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.024	0.052	-10000	0	-0.28	17	17
PPARGC1A	-0.027	0.14	-10000	0	-0.4	57	57
FHL2	0.027	0	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.036	0.012	-10000	0	-10000	0	0
HIST2H4A	0.01	0.033	0.27	1	-0.3	4	5
SIRT1/FOXO3a	0.018	0.025	-10000	0	-0.2	2	2
SIRT1	0.025	0.01	0.2	1	-10000	0	1
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	0.016	0.045	-10000	0	-0.2	3	3
apoptosis	-0.049	0.016	-10000	0	-10000	0	0
SIRT1/PGC1A	0	0.089	-10000	0	-0.23	57	57
p53/SIRT1	0.027	0.021	0.38	1	-10000	0	1
SIRT1/FOXO4	0.023	0.032	-10000	0	-0.2	2	2
FOXO1/FHL2/SIRT1	0.038	0.026	-10000	0	-0.21	1	1
HIST1H1E	0.007	0.035	0.2	2	-0.24	1	3
SIRT1/p300	0.036	0.012	-10000	0	-10000	0	0
muscle cell differentiation	-0.02	0.054	0.24	17	-0.22	3	20
TP53	0.02	0.013	0.2	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	-0.086	0.15	-10000	0	-0.28	172	172
ACSS2	0.008	0.017	0.35	1	-10000	0	1
SIRT1/PCAF/MYOD	0.021	0.055	0.22	3	-0.24	17	20

×

FAS signaling pathway (CD95)

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
SPTAN1	0.002	0.038	0.22	10	-10000	0	10
RFC1	0.001	0.032	0.19	12	-10000	0	12
PRKDC	0.019	0.071	0.23	44	-10000	0	44
RIPK1	0.028	0.004	-10000	0	-10000	0	0
CASP7	0.005	0.1	-10000	0	-0.54	12	12
FASLG/FAS/FADD/FAF1	0.004	0.066	0.21	11	-0.23	21	32
MAP2K4	-0.02	0.1	-10000	0	-0.33	24	24
mol:ceramide	0	0.086	-10000	0	-0.29	28	28
GSN	0	0.044	0.22	10	-0.22	4	14
FASLG/FAS/FADD/FAF1/Caspase 8	0	0.077	0.27	1	-0.29	19	20
FAS	0.02	0.045	-10000	0	-0.4	5	5
BID	-0.008	0.054	0.26	17	-0.27	1	18
MAP3K1	0.004	0.085	0.21	5	-0.35	13	18
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
RB1	0.026	0.079	0.22	60	-10000	0	60
CFLAR	0.028	0.002	-10000	0	-10000	0	0
HGF/MET	0.033	0.075	-10000	0	-0.26	27	27
ARHGDIB	0.002	0.037	0.23	8	-10000	0	8
FADD	0.025	0.008	-10000	0	-10000	0	0
actin filament polymerization	0.002	0.054	0.22	4	-0.23	12	16
NFKB1	-0.009	0.12	-10000	0	-0.68	13	13
MAPK8	-0.028	0.11	-10000	0	-0.42	18	18
DFFA	0.001	0.032	0.19	12	-10000	0	12
DNA fragmentation during apoptosis	0	0.047	0.2	16	-10000	0	16
FAS/FADD/MET	0.044	0.046	0.25	1	-0.25	9	10
CFLAR/RIP1	0.041	0.006	-10000	0	-10000	0	0
FAIM3	0.004	0.095	-10000	0	-0.4	24	24
FAF1	0.02	0.017	-10000	0	-10000	0	0
PARP1	0.001	0.032	0.19	12	-10000	0	12
DFFB	0.002	0.035	0.19	14	-10000	0	14
CHUK	-0.012	0.12	-10000	0	-0.63	13	13
FASLG	-0.006	0.1	-10000	0	-0.4	28	28
FAS/FADD	0.033	0.036	-10000	0	-0.28	5	5
HGF	0.017	0.06	-10000	0	-0.4	9	9
LMNA	-0.002	0.042	0.26	4	-10000	0	4
CASP6	0.001	0.032	0.19	12	-10000	0	12
CASP10	0.026	0.007	-10000	0	-10000	0	0
CASP3	0.006	0.048	0.25	15	-10000	0	15
PTPN13	0.012	0.08	-10000	0	-0.42	15	15
CASP8	-0.002	0.076	0.32	23	-10000	0	23
IL6	-0.037	0.2	-10000	0	-0.85	16	16
MET	0.023	0.046	0.36	1	-0.43	4	5
ICAD/CAD	0	0.031	0.18	9	-10000	0	9
FASLG/FAS/FADD/FAF1/Caspase 10	0	0.087	-10000	0	-0.29	28	28
activation of caspase activity by cytochrome c	-0.008	0.054	0.25	17	-0.26	1	18
PAK2	0.002	0.035	0.19	14	-10000	0	14
BCL2	0.012	0.059	-10000	0	-0.4	9	9

×

Regulation of p38-alpha and p38-beta

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
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	0.003	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.023	0.04	-10000	0	-0.4	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.022	0.011	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.014	0.012	-10000	0	-0.18	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.022	0.022	-10000	0	-0.4	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	0.004	-10000	0	-10000	0	0
MAP3K12	0.027	0.002	-10000	0	-10000	0	0
FGR	0.022	0.041	-10000	0	-0.4	4	4
p38 alpha/TAB1	-0.064	0.11	-10000	0	-0.32	55	55
PRKG1	0.007	0.087	-10000	0	-0.4	20	20
DUSP8	0.026	0.02	-10000	0	-0.4	1	1
PGK/cGMP/p38 alpha	-0.031	0.14	0.16	8	-0.35	47	55
apoptosis	-0.062	0.11	-10000	0	-0.31	55	55
RAL/GTP	0.034	0.011	-10000	0	-10000	0	0
LYN	0.024	0.009	-10000	0	-10000	0	0
DUSP1	0.025	0.028	-10000	0	-0.4	2	2
PAK1	0.027	0.003	-10000	0	-10000	0	0
SRC	0.017	0.013	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.052	0.033	-10000	0	-0.21	1	1
TRAF6	0.027	0.004	-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	0.024	0.021	-10000	0	-0.4	1	1
RAC1-CDC42/GTP	0.03	0.019	-10000	0	-0.23	1	1
MAPK11	-0.011	0.15	0.24	29	-0.36	29	58
BLK	-0.1	0.19	-10000	0	-0.4	129	129
HCK	0.01	0.053	-10000	0	-0.4	7	7
MAP2K3	0.023	0.01	-10000	0	-10000	0	0
DUSP16	0.027	0.004	-10000	0	-10000	0	0
DUSP10	0.023	0.043	-10000	0	-0.43	4	4
TRAF6/MEKK3	0.034	0.008	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.023	0.16	0.21	28	-0.36	51	79
positive regulation of innate immune response	-0.023	0.18	0.26	30	-0.41	42	72
LCK	0.017	0.063	-10000	0	-0.42	9	9
p38alpha-beta/MKP7	-0.014	0.18	0.27	27	-0.4	39	66
p38alpha-beta/MKP5	-0.013	0.17	0.27	27	-0.4	40	67
PGK/cGMP	0.006	0.061	-10000	0	-0.28	20	20
PAK2	0.027	0.002	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.015	0.18	0.26	28	-0.41	39	67
CDC42	0.025	0.021	-10000	0	-0.4	1	1
RALB	0.027	0.001	-10000	0	-10000	0	0
RALA	0.025	0.008	-10000	0	-10000	0	0
PAK3	0.009	0.022	-10000	0	-10000	0	0

×

Glypican 2 network

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
MDK	0.023	0.043	-10000	0	-0.43	4	4
GPC2	0.013	0.081	0.36	1	-0.43	14	15
GPC2/Midkine	0.025	0.069	0.26	1	-0.3	18	19
neuron projection morphogenesis	0.025	0.068	0.26	1	-0.3	18	19

×

Signaling events mediated by PTP1B

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
PDGFRB	0.022	0.048	-10000	0	-0.43	5	5
Jak2/Leptin Receptor	0.023	0.085	-10000	0	-0.44	5	5
PTP1B/AKT1	0.017	0.074	0.18	3	-0.29	4	7
FYN	0.027	0.004	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.013	0.08	0.2	8	-0.31	4	12
EGFR	0.018	0.027	-10000	0	-0.4	1	1
EGF/EGFR	-0.013	0.11	-10000	0	-0.27	34	34
CSF1	0.026	0.021	-10000	0	-0.4	1	1
AKT1	0.026	0.008	-10000	0	-10000	0	0
INSR	0.027	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.005	0.081	0.2	5	-0.28	10	15
Insulin Receptor/Insulin	0.03	0.067	-10000	0	-0.31	2	2
HCK	0.01	0.053	-10000	0	-0.4	7	7
CRK	0.023	0.01	-10000	0	-10000	0	0
TYK2	0.011	0.078	0.25	6	-0.32	3	9
EGF	-0.059	0.17	-10000	0	-0.4	89	89
YES1	0.022	0.022	-10000	0	-0.4	1	1
CAV1	0.022	0.1	0.21	36	-0.28	5	41
TXN	0.027	0.004	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.028	0.084	-10000	0	-0.35	2	2
cell migration	-0.013	0.08	0.31	4	-0.2	8	12
STAT3	0.027	0.004	-10000	0	-10000	0	0
PRLR	0.018	0.06	-10000	0	-0.4	9	9
ITGA2B	0.005	0.089	-10000	0	-0.43	18	18
CSF1R	0.001	0.1	-10000	0	-0.4	28	28
Prolactin Receptor/Prolactin	0.019	0.07	-10000	0	-0.29	21	21
FGR	0.022	0.041	-10000	0	-0.4	4	4
PTP1B/p130 Cas	0.02	0.081	0.2	6	-0.3	4	10
Crk/p130 Cas	0.018	0.078	0.2	2	-0.3	3	5
DOK1	0.016	0.073	0.22	2	-0.32	3	5
JAK2	0.015	0.085	-10000	0	-0.38	8	8
Jak2/Leptin Receptor/Leptin	0.021	0.091	-10000	0	-0.36	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
PTPN1	0.013	0.08	0.2	8	-0.31	4	12
LYN	0.024	0.009	-10000	0	-10000	0	0
CDH2	0.004	0.084	-10000	0	-0.4	18	18
SRC	0.025	0.086	-10000	0	-0.4	11	11
ITGB3	0.022	0.045	-10000	0	-0.4	5	5
CAT1/PTP1B	0	0.16	0.24	52	-0.44	18	70
CAPN1	0.026	0.004	-10000	0	-10000	0	0
CSK	0.026	0.006	-10000	0	-10000	0	0
PI3K	0.043	0.064	-10000	0	-0.29	2	2
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.023	0.084	-10000	0	-0.35	1	1
negative regulation of transcription	0.015	0.084	-10000	0	-0.38	8	8
FCGR2A	0.024	0.037	-10000	0	-0.43	3	3
FER	0.026	0.007	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.021	0.074	-10000	0	-0.3	23	23
BLK	-0.1	0.19	-10000	0	-0.4	129	129
Insulin Receptor/Insulin/Shc	0.046	0.013	-10000	0	-10000	0	0
RHOA	0.026	0.004	-10000	0	-10000	0	0
LEPR	0.021	0.044	-10000	0	-0.39	5	5
BCAR1	0.026	0.02	-10000	0	-0.4	1	1
p210 bcr-abl/Grb2	0.027	0.004	-10000	0	-10000	0	0
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.073	0.19	0.24	14	-0.43	58	72
PRL	-0.006	0.073	-10000	0	-0.42	12	12
SOCS3	0.011	0.12	-10000	0	-1.1	5	5
SPRY2	0.022	0.012	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.047	0.011	-10000	0	-10000	0	0
CSF1/CSF1R	0.016	0.097	0.23	2	-0.32	8	10
Ras protein signal transduction	-0.006	0.053	0.43	5	-10000	0	5
IRS1	0.027	0.002	-10000	0	-10000	0	0
INS	0.008	0.016	-10000	0	-10000	0	0
LEP	-0.014	0.11	-10000	0	-0.4	33	33
STAT5B	0.02	0.076	0.19	5	-0.3	6	11
STAT5A	0.02	0.076	0.19	5	-0.3	6	11
GRB2	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.018	0.086	0.2	5	-0.32	6	11
CSN2	-0.007	0.052	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
LAT	0.029	0.059	-10000	0	-0.46	4	4
YBX1	0.035	0.008	-10000	0	-10000	0	0
LCK	0.017	0.063	-10000	0	-0.42	9	9
SHC1	0.027	0.004	-10000	0	-10000	0	0
NOX4	-0.2	0.23	0.36	1	-0.43	229	230

×

IL6-mediated signaling events

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
BCL2L1	0.066	0.15	0.42	1	-0.66	2	3
CRP	0.003	0.14	0.48	1	-0.72	3	4
cell cycle arrest	0.002	0.14	-10000	0	-0.7	5	5
TIMP1	0.006	0.15	-10000	0	-0.6	5	5
IL6ST	0.022	0.057	-10000	0	-0.39	8	8
Rac1/GDP	-0.038	0.13	-10000	0	-0.38	30	30
AP1	0.053	0.09	-10000	0	-0.46	4	4
GAB2	0.028	0.004	-10000	0	-10000	0	0
TNFSF11	0.032	0.18	0.44	2	-0.77	7	9
HSP90B1	0.035	0.051	-10000	0	-0.58	1	1
GAB1	0.027	0.005	-10000	0	-10000	0	0
MAPK14	-0.035	0.12	-10000	0	-0.39	18	18
AKT1	0.033	0.041	-10000	0	-0.4	1	1
FOXO1	0.06	0.076	0.25	4	-0.36	1	5
MAP2K6	-0.045	0.12	-10000	0	-0.38	25	25
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.032	0.12	0.4	1	-0.44	14	15
MITF	-0.045	0.12	0.18	2	-0.38	27	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	0.003	0.17	-10000	0	-1.2	9	9
CEBPB	0.019	0.016	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.023	0.081	0.25	1	-0.42	5	6
STAT3	-0.006	0.15	-10000	0	-0.74	5	5
STAT1	0.02	0.017	-10000	0	-10000	0	0
CEBPD	0.02	0.15	-10000	0	-0.98	2	2
PIK3CA	0.028	0.002	-10000	0	-10000	0	0
PI3K	0.041	0.009	-10000	0	-10000	0	0
JUN	0.027	0.005	-10000	0	-10000	0	0
PIAS3/MITF	-0.029	0.13	0.22	1	-0.38	23	24
MAPK11	-0.033	0.12	-10000	0	-0.4	17	17
STAT3 (dimer)/FOXO1	0.049	0.15	0.35	15	-0.56	4	19
GRB2/SOS1/GAB family	0.017	0.14	0.25	2	-0.41	14	16
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.031	0.12	0.23	2	-0.4	23	25
GRB2	0.027	0.005	-10000	0	-10000	0	0
JAK2	0.024	0.035	-10000	0	-0.4	3	3
LBP	0.07	0.16	0.38	16	-0.58	1	17
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	0.028	0.008	-10000	0	-10000	0	0
MYC	0.031	0.15	0.45	2	-0.68	3	5
FGG	-0.011	0.14	-10000	0	-0.69	4	4
macrophage differentiation	0.002	0.14	-10000	0	-0.7	5	5
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.026	0.15	0.26	4	-0.31	39	43
JUNB	0.001	0.14	-10000	0	-0.83	4	4
FOS	0.023	0.035	-10000	0	-0.4	3	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.04	0.13	0.2	2	-0.39	28	30
STAT1/PIAS1	-0.008	0.12	-10000	0	-0.38	16	16
GRB2/SOS1/GAB family/SHP2/PI3K	0.037	0.04	-10000	0	-0.34	3	3
STAT3 (dimer)	0	0.15	-10000	0	-0.73	5	5
PRKCD	-0.013	0.14	0.32	20	-0.5	9	29
IL6R	-0.065	0.17	-10000	0	-0.39	99	99
SOCS3	-0.032	0.12	-10000	0	-0.5	5	5
gp130 (dimer)/JAK1/JAK1/LMO4	0.054	0.044	-10000	0	-0.23	8	8
Rac1/GTP	-0.036	0.13	-10000	0	-0.38	30	30
HCK	0.01	0.053	-10000	0	-0.4	7	7
MAPKKK cascade	0.04	0.082	-10000	0	-0.5	4	4
bone resorption	0.033	0.17	0.4	5	-0.72	7	12
IRF1	0.004	0.13	-10000	0	-0.68	3	3
mol:GDP	-0.041	0.13	0.19	2	-0.38	34	36
SOS1	0.028	0.003	-10000	0	-10000	0	0
VAV1	-0.048	0.13	0.19	2	-0.38	34	36
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.07	0.17	-10000	0	-0.49	30	30
PTPN11	0.016	0.068	-10000	0	-0.79	3	3
IL6/IL6RA	-0.072	0.17	0.26	4	-0.3	148	152
gp130 (dimer)/TYK2/TYK2/LMO4	0.05	0.042	-10000	0	-0.23	8	8
gp130 (dimer)/JAK2/JAK2/LMO4	0.048	0.048	-10000	0	-0.23	11	11
IL6	-0.039	0.17	0.36	5	-0.42	70	75
PIAS3	0.026	0.006	-10000	0	-10000	0	0
PTPRE	0.022	0.01	-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	-0.045	0.12	0.18	3	-0.33	35	38
LMO4	0.029	0.009	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.006	0.15	-10000	0	-0.7	5	5
MCL1	0.034	0.047	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.048	-10000	0	-0.43	5	5
mol:S1P	0.001	0.002	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.039	0.11	-10000	0	-0.3	36	36
GNAO1	-0.087	0.19	-10000	0	-0.4	122	122
S1P/S1P3/G12/G13	0.045	0.025	-10000	0	-0.23	1	1
AKT1	-0.028	0.14	-10000	0	-0.47	36	36
AKT3	-0.015	0.16	-10000	0	-1.2	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.022	0.048	-10000	0	-0.43	5	5
GNAI2	0.027	0.009	-10000	0	-10000	0	0
GNAI3	0.027	0.008	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.026	0.023	-10000	0	-0.42	1	1
S1PR2	0.027	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.042	0.13	-10000	0	-0.37	34	34
MAPK3	-0.046	0.12	-10000	0	-0.36	34	34
MAPK1	-0.038	0.12	-10000	0	-0.38	24	24
JAK2	0.001	0.14	0.23	8	-0.36	30	38
CXCR4	-0.046	0.12	-10000	0	-0.35	34	34
FLT1	0.021	0.015	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
SRC	-0.032	0.1	-10000	0	-0.35	23	23
S1P/S1P3/Gi	-0.043	0.13	-10000	0	-0.37	34	34
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.031	0.13	-10000	0	-0.34	34	34
VEGFA	0.029	0.019	0.36	1	-10000	0	1
S1P/S1P2/Gi	-0.044	0.13	-10000	0	-0.34	35	35
VEGFR1 homodimer/VEGFA homodimer	0.034	0.026	0.27	1	-10000	0	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.022	0.037	-10000	0	-0.3	4	4
GNAQ	0.026	0.02	-10000	0	-0.4	1	1
GNAZ	0.021	0.045	-10000	0	-0.4	5	5
G12/G13	0.036	0.013	-10000	0	-10000	0	0
GNA14	0.025	0.028	-10000	0	-0.4	2	2
GNA15	0.022	0.048	-10000	0	-0.43	5	5
GNA12	0.025	0.008	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.025	0.028	-10000	0	-0.4	2	2
Rac1/GTP	-0.032	0.12	-10000	0	-0.35	33	33

×

Regulation of nuclear SMAD2/3 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
EP300	0.026	0.023	-10000	0	-10000	0	0
HSPA8	0.026	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.002	0.11	-10000	0	-0.31	31	31
AKT1	-0.012	0.055	-10000	0	-10000	0	0
GSC	-0.038	0.13	-10000	0	-0.51	8	8
NKX2-5	0	0.01	-10000	0	-10000	0	0
muscle cell differentiation	0.042	0.12	0.37	12	-10000	0	12
SMAD2-3/SMAD4/SP1	-0.014	0.12	-10000	0	-0.3	2	2
SMAD4	0.001	0.048	-10000	0	-10000	0	0
CBFB	0.027	0.002	-10000	0	-10000	0	0
SAP18	0.021	0.011	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.034	0.14	-10000	0	-0.25	132	132
SMAD3/SMAD4/VDR	0.058	0.06	-10000	0	-10000	0	0
MYC	0.049	0.06	0.37	5	-0.36	2	7
CDKN2B	-0.5	0.64	-10000	0	-1.3	178	178
AP1	0.014	0.054	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.018	0.12	-10000	0	-0.34	40	40
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.16	0.23	-10000	0	-0.43	165	165
SP3	0.029	0.001	-10000	0	-10000	0	0
CREB1	0.027	0	-10000	0	-10000	0	0
FOXH1	0.005	0.078	0.36	1	-0.4	14	15
SMAD3/SMAD4/GR	0.009	0.1	-10000	0	-0.3	28	28
GATA3	0.016	0.058	-10000	0	-0.42	5	5
SKI/SIN3/HDAC complex/NCoR1	0.019	0.066	-10000	0	-0.44	4	4
MEF2C/TIF2	-0.003	0.086	-10000	0	-0.4	8	8
endothelial cell migration	0.02	0.12	-10000	0	-10000	0	0
MAX	0.029	0.012	-10000	0	-10000	0	0
RBBP7	0.027	0.003	-10000	0	-10000	0	0
RBBP4	0.026	0.006	-10000	0	-10000	0	0
RUNX2	0.027	0.003	-10000	0	-10000	0	0
RUNX3	0.025	0.021	-10000	0	-0.4	1	1
RUNX1	0.026	0.006	-10000	0	-10000	0	0
CTBP1	0.027	0.005	-10000	0	-10000	0	0
NR3C1	0.002	0.11	-10000	0	-0.4	30	30
VDR	0.027	0.003	-10000	0	-10000	0	0
CDKN1A	-0.014	0.11	-10000	0	-1	3	3
KAT2B	0.013	0.08	-10000	0	-0.39	17	17
SMAD2/SMAD2/SMAD4/FOXH1	-0.004	0.082	0.28	1	-0.3	8	9
DCP1A	0.027	0.004	-10000	0	-10000	0	0
SKI	0.025	0.007	-10000	0	-10000	0	0
SERPINE1	-0.02	0.12	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	0.018	0.065	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.016	0.069	-10000	0	-0.29	2	2
SAP30	0.026	0.006	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.055	0.048	-10000	0	-10000	0	0
JUN	0.003	0.046	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.018	0.067	-10000	0	-10000	0	0
TFE3	0.018	0.024	-10000	0	-10000	0	0
COL1A2	0.003	0.08	-10000	0	-0.3	1	1
mesenchymal cell differentiation	-0.018	0.065	-10000	0	-10000	0	0
DLX1	0	0.084	-10000	0	-0.43	16	16
TCF3	0.027	0.004	-10000	0	-10000	0	0
FOS	0.02	0.038	-10000	0	-0.4	3	3
SMAD3/SMAD4/Max	0.026	0.071	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.055	0.019	-10000	0	-10000	0	0
ZBTB17	0.046	0.039	-10000	0	-0.4	1	1
LAMC1	-0.003	0.043	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.016	0.058	0.28	3	-0.31	1	4
IRF7	0.026	0.02	-10000	0	-0.4	1	1
ESR1	-0.012	0.12	-10000	0	-0.4	39	39
HNF4A	0.016	0.014	-10000	0	-10000	0	0
MEF2C	-0.002	0.096	-10000	0	-0.42	8	8
SMAD2-3/SMAD4	-0.005	0.092	-10000	0	-0.28	2	2
Cbp/p300/Src-1	0.058	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	0.011	0.011	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.021	0.049	0.36	7	-0.43	1	8
CREBBP	0.029	0.013	-10000	0	-10000	0	0
SKIL	0.026	0.02	-10000	0	-0.4	1	1
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC2	0.026	0.004	-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	0.063	-10000	0	-10000	0	0
MSG1/HSC70	-0.065	0.16	-10000	0	-0.31	134	134
SMAD2	-0.009	0.049	-10000	0	-10000	0	0
SMAD3	0	0.051	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.004	0.047	0.21	4	-0.25	2	6
SMAD2/SMAD2/SMAD4	-0.052	0.12	-10000	0	-0.35	36	36
NCOR1	0.022	0.011	-10000	0	-10000	0	0
NCOA2	0.023	0.022	-10000	0	-0.4	1	1
NCOA1	0.027	0.001	-10000	0	-10000	0	0
MYOD/E2A	0.032	0.006	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.005	0.12	-10000	0	-0.32	1	1
IFNB1	-0.008	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.004	0.11	-10000	0	-0.43	8	8
CITED1	-0.11	0.21	-10000	0	-0.43	134	134
SMAD2-3/SMAD4/ARC105	0.006	0.092	-10000	0	-0.25	1	1
RBL1	0.017	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.16	0.28	-10000	0	-0.53	155	155
RUNX1-3/PEBPB2	0.05	0.017	-10000	0	-10000	0	0
SMAD7	-0.008	0.096	-10000	0	-0.47	4	4
MYC/MIZ-1	0.072	0.079	0.2	50	-0.3	2	52
SMAD3/SMAD4	0.008	0.1	0.25	12	-0.34	5	17
IL10	-0.022	0.12	-10000	0	-0.45	27	27
PIASy/HDAC complex	0.012	0.025	-10000	0	-10000	0	0
PIAS3	0.028	0.007	-10000	0	-10000	0	0
CDK2	0.031	0.009	-10000	0	-10000	0	0
IL5	-0.014	0.078	-10000	0	-0.38	6	6
CDK4	0.027	0.028	-10000	0	-0.42	1	1
PIAS4	0.012	0.025	-10000	0	-10000	0	0
ATF3	0.024	0.037	-10000	0	-0.43	3	3
SMAD3/SMAD4/SP1	0	0.085	-10000	0	-10000	0	0
FOXG1	-0.072	0.15	-10000	0	-0.44	65	65
FOXO3	-0.028	0.061	-10000	0	-10000	0	0
FOXO1	-0.02	0.052	-10000	0	-0.35	1	1
FOXO4	-0.027	0.059	-10000	0	-10000	0	0
heart looping	-0.002	0.095	-10000	0	-0.42	8	8
CEBPB	0	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.006	0.083	-10000	0	-0.28	11	11
MYOD1	-0.018	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.013	0.049	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	0.01	0.094	-10000	0	-0.3	12	12
SnoN/SIN3/HDAC complex/NCoR1	0.026	0.02	-10000	0	-0.4	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.035	0.069	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.013	0.086	-10000	0	-10000	0	0
MED15	0.025	0.021	-10000	0	-0.4	1	1
SP1	0	0.039	-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	0.079	0.26	1	-0.28	11	12
ITGB5	-0.011	0.057	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.026	0.053	-10000	0	-0.44	2	2
SMAD3/SMAD4/AR	0.002	0.094	-10000	0	-0.31	16	16
AR	-0.004	0.099	-10000	0	-0.4	26	26
negative regulation of cell growth	-0.006	0.068	-10000	0	-0.31	6	6
SMAD3/SMAD4/MYOD	0.012	0.065	-10000	0	-10000	0	0
E2F5	0.026	0.05	0.36	6	-0.43	2	8
E2F4	0.027	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.021	0.076	0.27	1	-0.31	1	2
SMAD2-3/SMAD4/FOXO1-3a-4	-0.13	0.24	-10000	0	-0.43	164	164
TFDP1	0.021	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.026	0.065	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.018	0.065	-10000	0	-10000	0	0
TGIF2	0.021	0.049	0.36	7	-0.43	1	8
TGIF1	0.022	0.011	-10000	0	-10000	0	0
ATF2	0.027	0.003	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.031	0.16	-10000	0	-0.63	26	26
oxygen homeostasis	-0.011	0.01	-10000	0	-10000	0	0
TCEB2	0.026	0.022	-10000	0	-0.43	1	1
TCEB1	0.024	0.01	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.043	0.073	-10000	0	-0.34	1	1
EPO	-0.15	0.15	-10000	0	-0.54	12	12
FIH (dimer)	0.007	0.023	-10000	0	-10000	0	0
APEX1	-0.015	0.024	-10000	0	-10000	0	0
SERPINE1	-0.2	0.22	-10000	0	-0.68	42	42
FLT1	-0.002	0.087	-10000	0	-0.6	8	8
ADORA2A	-0.16	0.17	0.36	1	-0.6	13	14
germ cell development	-0.16	0.17	-10000	0	-0.53	37	37
SLC11A2	-0.16	0.17	-10000	0	-0.62	11	11
BHLHE40	-0.17	0.18	-10000	0	-0.57	24	24
HIF1AN	0.007	0.023	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.091	0.11	-10000	0	-0.4	3	3
ETS1	0.036	0.022	-10000	0	-0.39	1	1
CITED2	-0.006	0.1	-10000	0	-0.72	8	8
KDR	-0.012	0.13	-10000	0	-0.66	15	15
PGK1	-0.16	0.17	-10000	0	-0.62	12	12
SIRT1	0.027	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.18	0.2	-10000	0	-0.61	40	40
EPAS1	-0.052	0.065	-10000	0	-0.32	1	1
SP1	0.031	0.01	-10000	0	-10000	0	0
ABCG2	-0.36	0.24	-10000	0	-0.64	111	111
EFNA1	-0.16	0.17	-10000	0	-0.62	12	12
FXN	-0.16	0.17	0.36	1	-0.61	12	13
POU5F1	-0.17	0.18	-10000	0	-0.55	37	37
neuron apoptosis	0.18	0.2	0.6	40	-10000	0	40
EP300	0.026	0.006	-10000	0	-10000	0	0
EGLN3	0.004	0.04	-10000	0	-0.4	3	3
EGLN2	0.007	0.03	-10000	0	-0.4	1	1
EGLN1	0.008	0.023	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.047	0.021	-10000	0	-10000	0	0
VHL	0.027	0.003	-10000	0	-10000	0	0
ARNT	-0.015	0.031	-10000	0	-0.41	1	1
SLC2A1	-0.16	0.18	0.36	1	-0.63	17	18
TWIST1	-0.16	0.19	0.36	1	-0.65	33	34
ELK1	0.032	0.003	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.091	0.11	-10000	0	-0.42	2	2
VEGFA	-0.16	0.17	-10000	0	-0.62	12	12
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.04	0.02	0.26	1	-0.27	1	2
PDGFRB	0.023	0.048	-10000	0	-0.43	5	5
SPHK1	-0.001	0.054	-10000	0	-0.6	3	3
mol:S1P	-0.004	0.049	-10000	0	-0.5	3	3
S1P1/S1P/Gi	-0.039	0.15	0.24	2	-0.4	37	39
GNAO1	-0.087	0.19	-10000	0	-0.4	122	122
PDGFB-D/PDGFRB/PLCgamma1	0.009	0.16	0.28	14	-0.41	19	33
PLCG1	-0.045	0.12	0.3	5	-0.4	25	30
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.048	-10000	0	-0.43	5	5
GNAI2	0.028	0.006	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
GNAI1	0.015	0.072	-10000	0	-0.4	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.006	0.016	0.2	1	-0.22	1	2
S1P1/S1P	0.023	0.059	0.21	3	-0.35	1	4
negative regulation of cAMP metabolic process	-0.038	0.15	0.24	2	-0.38	37	39
MAPK3	-0.043	0.16	0.26	3	-0.46	26	29
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
KDR	0.026	0.02	-10000	0	-0.39	1	1
PLCB2	0.024	0.061	0.24	7	-0.32	1	8
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	0.017	0.047	-10000	0	-0.3	1	1
receptor internalization	0.021	0.055	0.19	2	-0.33	1	3
PTGS2	-0.04	0.17	-10000	0	-0.64	12	12
Rac1/GTP	0.014	0.046	-10000	0	-0.3	1	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
VEGFA	0.028	0.016	0.36	1	-10000	0	1
negative regulation of T cell proliferation	-0.038	0.15	0.24	2	-0.38	37	39
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.022	0.046	-10000	0	-0.4	5	5
MAPK1	-0.039	0.15	0.27	1	-0.47	23	24
S1P1/S1P/PDGFB-D/PDGFRB	0.042	0.081	0.24	7	-0.28	2	9
ABCC1	0.028	0.004	-10000	0	-10000	0	0

×

Aurora B signaling

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
Condensin I complex	0.009	0.048	-10000	0	-0.38	1	1
STMN1	0.013	0.016	-10000	0	-0.28	1	1
Aurora B/RasGAP/Survivin	0.051	0.028	0.25	1	-10000	0	1
Chromosomal passenger complex/Cul3 protein complex	-0.014	0.084	0.16	1	-0.28	19	20
BIRC5	0.03	0.016	0.36	1	-10000	0	1
DES	-0.39	0.32	-10000	0	-0.6	299	299
Aurora C/Aurora B/INCENP	0.046	0.03	-10000	0	-0.21	2	2
Aurora B/TACC1	0.03	0.018	-10000	0	-10000	0	0
Aurora B/PP2A	0.036	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	0.016	0.098	-10000	0	-0.23	59	59
KIF2C	0.014	0.052	-10000	0	-0.35	7	7
PEBP1	0.029	0.002	-10000	0	-10000	0	0
KIF20A	0.028	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.036	0.018	-10000	0	-10000	0	0
SEPT1	0.022	0.049	-10000	0	-0.4	6	6
SMC2	0.026	0.02	-10000	0	-0.4	1	1
SMC4	0.025	0.028	-10000	0	-0.4	2	2
NSUN2/NPM1/Nucleolin	-0.072	0.2	-10000	0	-0.49	80	80
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	0.014	0.007	-10000	0	-10000	0	0
AURKB	0.028	0.014	-10000	0	-10000	0	0
AURKC	0.023	0.03	-10000	0	-0.4	2	2
CDCA8	0.029	0.006	-10000	0	-10000	0	0
cytokinesis	0.007	0.038	-10000	0	-0.37	2	2
Aurora B/Septin1	0.003	0.11	-10000	0	-0.38	3	3
AURKA	0.016	0.014	-10000	0	-10000	0	0
INCENP	0.029	0.005	-10000	0	-10000	0	0
KLHL13	-0.029	0.14	-10000	0	-0.4	59	59
BUB1	0.029	0.004	-10000	0	-10000	0	0
hSgo1/Aurora B/Survivin	0.049	0.029	0.24	1	-0.21	1	2
EVI5	0.028	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.046	0.063	-10000	0	-0.29	1	1
SGOL1	0.026	0.022	-10000	0	-0.43	1	1
CENPA	0.032	0.056	-10000	0	-10000	0	0
NCAPG	0.027	0.005	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.036	0.018	-10000	0	-10000	0	0
NCAPD2	0.027	0.004	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.037	0.018	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
NCAPH	0.027	0	-10000	0	-10000	0	0
NPM1	-0.04	0.14	-10000	0	-0.32	63	63
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	0.036	0.018	-10000	0	-10000	0	0
PPP1CC	0.027	0.003	-10000	0	-10000	0	0
Centraspindlin	0.042	0.063	-10000	0	-0.31	1	1
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
NSUN2	-0.034	0.11	-10000	0	-0.28	75	75
MYLK	-0.023	0.095	-10000	0	-0.27	58	58
KIF23	0.026	0.022	-10000	0	-0.43	1	1
VIM	0.014	0.007	-10000	0	-10000	0	0
RACGAP1	0.028	0.004	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.035	0.11	-10000	0	-0.28	76	76
Chromosomal passenger complex	0.02	0.049	0.17	1	-10000	0	1
Chromosomal passenger complex/EVI5	0.091	0.055	0.3	1	-10000	0	1
TACC1	0.023	0.01	-10000	0	-10000	0	0
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
CUL3	0.027	0.001	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

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	-0.006	0.016	-10000	0	-0.22	2	2
RAS family/GTP	0.011	0.093	0.23	2	-0.26	6	8
NFATC4	-0.022	0.062	0.25	3	-10000	0	3
ERBB2IP	0.021	0.048	-10000	0	-0.39	6	6
HSP90 (dimer)	0.025	0.007	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.001	0.074	0.2	1	-10000	0	1
JUN	0.006	0.064	-10000	0	-0.18	1	1
HRAS	0.026	0.02	-10000	0	-0.4	1	1
DOCK7	-0.028	0.066	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.015	0.081	0.22	7	-0.22	41	48
AKT1	0.004	0.006	-10000	0	-10000	0	0
BAD	-0.006	0.012	-10000	0	-0.24	1	1
MAPK10	-0.022	0.072	0.18	5	-0.24	12	17
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.001	0.08	0.21	1	-10000	0	1
RAF1	-0.007	0.088	0.24	3	-0.3	6	9
ErbB2/ErbB3/neuregulin 2	-0.002	0.087	0.2	9	-0.22	51	60
STAT3	0.019	0.043	-10000	0	-0.79	1	1
cell migration	-0.015	0.071	0.19	8	-0.21	12	20
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	-0.045	0.22	-10000	0	-0.59	54	54
FOS	-0.019	0.14	-10000	0	-0.36	48	48
NRAS	0.025	0.029	-10000	0	-0.4	2	2
mol:Ca2+	-0.001	0.074	0.2	1	-10000	0	1
MAPK3	-0.027	0.17	-10000	0	-0.49	40	40
MAPK1	-0.044	0.2	-10000	0	-0.55	48	48
JAK2	-0.029	0.067	0.17	1	-10000	0	1
NF2	0.003	0.065	-10000	0	-0.6	5	5
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.006	0.072	0.18	1	-0.22	41	42
NRG1	-0.022	0.13	-10000	0	-0.4	45	45
GRB2/SOS1	0.04	0.007	-10000	0	-10000	0	0
MAPK8	-0.017	0.092	-10000	0	-0.26	8	8
MAPK9	-0.006	0.054	0.18	5	-10000	0	5
ERBB2	-0.013	0.047	0.29	10	-10000	0	10
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	0.004	0.013	0.21	1	-10000	0	1
STAT3 (dimer)	0.019	0.042	-10000	0	-0.77	1	1
RNF41	-0.009	0.014	-10000	0	-0.2	2	2
FRAP1	-0.003	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.011	0.05	-10000	0	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	0.011	0.036	0.22	10	-10000	0	10
CHRNA1	-0.036	0.2	0.25	1	-0.61	42	43
myelination	-0.019	0.064	0.25	4	-10000	0	4
PPP3CB	-0.027	0.063	0.16	1	-10000	0	1
KRAS	0.027	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.01	0.081	0.24	1	-10000	0	1
NRG2	-0.04	0.14	-10000	0	-0.4	59	59
mol:GDP	-0.006	0.072	0.18	1	-0.22	41	42
SOS1	0.027	0.002	-10000	0	-10000	0	0
MAP2K2	-0.015	0.092	0.24	3	-0.33	9	12
SRC	0.017	0.013	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.028	0.067	0.17	1	-10000	0	1
MAP2K1	-0.048	0.2	-10000	0	-0.57	38	38
heart morphogenesis	-0.001	0.074	0.2	1	-10000	0	1
RAS family/GDP	0.015	0.093	0.25	2	-10000	0	2
GRB2	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.006	0.069	-10000	0	-0.64	5	5
CHRNE	0.006	0.023	-10000	0	-0.14	7	7
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
activation of caspase activity	-0.004	0.006	-10000	0	-10000	0	0
nervous system development	-0.001	0.074	0.2	1	-10000	0	1
CDC42	0.025	0.021	-10000	0	-0.4	1	1

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.021	0.052	-10000	0	-0.42	6	6
ANTXR2	0.026	0.02	-10000	0	-0.4	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.006	-10000	0	-0.052	7	7
monocyte activation	-0.006	0.095	-10000	0	-0.33	36	36
MAP2K2	0.006	0.079	-10000	0	-0.58	8	8
MAP2K1	-0.003	0.006	-10000	0	-10000	0	0
MAP2K7	-0.004	0.011	-10000	0	-0.2	1	1
MAP2K6	-0.005	0.019	-10000	0	-0.2	4	4
CYAA	-0.008	0.025	-10000	0	-0.21	7	7
MAP2K4	-0.003	0.006	-10000	0	-10000	0	0
IL1B	-0.025	0.066	-10000	0	-0.21	50	50
Channel	0.03	0.033	-10000	0	-0.22	7	7
NLRP1	-0.004	0.018	-10000	0	-0.21	3	3
CALM1	0.025	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.019	0.1	-10000	0	-0.38	35	35
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.006	0.052	7	-10000	0	7
MAPK3	-0.004	0.011	-10000	0	-0.2	1	1
MAPK1	-0.003	0.006	-10000	0	-10000	0	0
PGR	-0.04	0.076	-10000	0	-0.2	84	84
PA/Cellular Receptors	0.032	0.036	-10000	0	-0.25	7	7
apoptosis	-0.001	0.006	-10000	0	-0.052	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.03	0.029	-10000	0	-0.2	7	7
macrophage activation	-0.004	0.02	0.18	4	-0.19	1	5
TNF	0.025	0.029	-10000	0	-0.4	2	2
VCAM1	-0.006	0.096	-10000	0	-0.33	36	36
platelet activation	-0.019	0.1	-10000	0	-0.38	35	35
MAPKKK cascade	0.001	0.014	0.14	1	-0.07	7	8
IL18	-0.003	0.017	-10000	0	-0.19	2	2
negative regulation of macrophage activation	-0.001	0.006	-10000	0	-0.052	7	7
LEF	-0.001	0.006	-10000	0	-0.052	7	7
CASP1	0	0.011	-10000	0	-0.1	4	4
mol:cAMP	-0.019	0.11	-10000	0	-0.38	35	35
necrosis	-0.001	0.006	-10000	0	-0.052	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.03	0.031	-10000	0	-0.21	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.01	0.019	0.12	4	-0.12	1	5
BUB1B	0.019	0.038	-10000	0	-0.13	1	1
PLK1	0.024	0.027	0.069	56	-0.099	2	58
PLK1S1	0.022	0.047	-10000	0	-0.17	14	14
KIF2A	0.018	0.026	0.25	1	-10000	0	1
regulation of mitotic centrosome separation	0.024	0.027	0.069	56	-0.098	2	58
GOLGA2	0.027	0.003	-10000	0	-10000	0	0
Hec1/SPC24	0.039	0.042	-10000	0	-0.2	6	6
WEE1	0.031	0.038	-10000	0	-0.31	2	2
cytokinesis	0.026	0.034	0.19	1	-10000	0	1
PP2A-alpha B56	0.055	0.084	-10000	0	-0.5	9	9
AURKA	0.025	0.022	-10000	0	-10000	0	0
PICH/PLK1	0.019	0.05	0.18	14	-0.19	3	17
CENPE	0.017	0.026	-10000	0	-0.22	1	1
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.019	0.026	0.25	1	-10000	0	1
PPP2CA	0.027	0.004	-10000	0	-10000	0	0
FZR1	0.026	0.02	-10000	0	-0.4	1	1
TPX2	0.04	0.04	0.1	59	-10000	0	59
PAK1	0.028	0.004	-10000	0	-10000	0	0
SPC24	0.02	0.062	0.36	1	-0.43	8	9
FBXW11	0.027	0.004	-10000	0	-10000	0	0
CLSPN	0.014	0.046	-10000	0	-0.21	16	16
GORASP1	0.027	0.003	-10000	0	-10000	0	0
metaphase	0	0.002	0.016	5	-0.011	1	6
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.011	0.015	0.037	56	-0.052	2	58
G2 phase of mitotic cell cycle	0.001	0.003	0.015	7	-10000	0	7
STAG2	0.027	0.003	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.014	0.051	-10000	0	-0.45	5	5
spindle elongation	0.024	0.027	0.069	56	-0.098	2	58
ODF2	0.029	0.004	-10000	0	-10000	0	0
BUB1	0.019	0.081	-10000	0	-0.54	9	9
TPT1	0.027	0.037	0.11	2	-0.16	7	9
CDC25C	0.019	0.036	-10000	0	-0.24	7	7
CDC25B	0.017	0.098	0.36	12	-0.42	15	27
SGOL1	0.01	0.02	0.12	1	-0.12	4	5
RHOA	0.027	0.004	-10000	0	-10000	0	0
CCNB1/CDK1	0.037	0.05	0.24	12	-10000	0	12
CDC14B	0.007	0.014	-10000	0	-0.28	1	1
CDC20	0.027	0.004	-10000	0	-10000	0	0
PLK1/PBIP1	0.018	0.02	-10000	0	-10000	0	0
mitosis	-0.001	0.002	-10000	0	-10000	0	0
FBXO5	0.017	0.028	0.13	1	-10000	0	1
CDC2	0.002	0.003	0.015	12	-10000	0	12
NDC80	0.023	0.011	-10000	0	-10000	0	0
metaphase plate congression	0.005	0.066	-10000	0	-0.21	35	35
ERCC6L	0.021	0.048	0.19	12	-0.24	1	13
NLP/gamma Tubulin	0.013	0.015	0.075	3	-10000	0	3
microtubule cytoskeleton organization	0.027	0.037	0.11	2	-0.16	7	9
G2/M transition DNA damage checkpoint	0	0.002	0.014	6	-10000	0	6
PPP1R12A	0.026	0.029	-10000	0	-0.4	2	2
interphase	0	0.002	0.014	6	-10000	0	6
PLK1/PRC1-2	0.05	0.026	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.06	0.023	-10000	0	-10000	0	0
RAB1A	0.027	0.002	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.027	0.03	0.064	155	-10000	0	155
mitotic prometaphase	0.001	0.005	0.018	35	-10000	0	35
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.026	0.17	1	-0.21	1	2
microtubule-based process	0.036	0.025	-10000	0	-10000	0	0
Golgi organization	0.024	0.027	0.069	56	-0.098	2	58
Cohesin/SA2	0.035	0.021	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.039	0.03	-10000	0	-0.39	2	2
KIF20A	0.027	0.004	-10000	0	-10000	0	0
APC/C/CDC20	0.037	0.024	-10000	0	-10000	0	0
PPP2R1A	0.027	0.003	-10000	0	-10000	0	0
chromosome segregation	0.017	0.02	-10000	0	-10000	0	0
PRC1	0.026	0.006	-10000	0	-10000	0	0
ECT2	0.017	0.031	0.19	1	-0.2	3	4
C13orf34	0.022	0.025	0.064	56	-0.071	2	58
NUDC	0.005	0.066	-10000	0	-0.21	35	35
regulation of attachment of spindle microtubules to kinetochore	0.019	0.037	-10000	0	-0.13	1	1
spindle assembly	0.018	0.023	0.085	9	-0.085	2	11
spindle stabilization	0.022	0.047	-10000	0	-0.17	14	14
APC/C/HCDH1	0.024	0.018	-10000	0	-0.23	2	2
MKLP2/PLK1	0.037	0.025	-10000	0	-10000	0	0
CCNB1	0.027	0.009	-10000	0	-10000	0	0
PPP1CB	0.027	0.02	-10000	0	-0.4	1	1
BTRC	0.026	0.006	-10000	0	-10000	0	0
ROCK2	0.026	0.036	-10000	0	-0.36	2	2
TUBG1	0.019	0.017	0.097	1	-0.13	1	2
G2/M transition of mitotic cell cycle	0.013	0.041	0.18	12	-10000	0	12
MLF1IP	0.007	0.003	-10000	0	-10000	0	0
INCENP	0.028	0.004	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.051	0.16	-10000	0	-0.4	82	82
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.026	0.022	-10000	0	-0.43	1	1
TCEB1	0.024	0.01	-10000	0	-10000	0	0
HIF1A/p53	0.013	0.058	-10000	0	-0.25	17	17
HIF1A	0.004	0.046	-10000	0	-0.26	12	12
COPS5	0.024	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.065	0.033	-10000	0	-10000	0	0
FIH (dimer)	0.026	0.006	-10000	0	-10000	0	0
CDKN2A	-0.071	0.19	0.36	2	-0.43	97	99
ARNT/IPAS	-0.018	0.12	-10000	0	-0.28	80	80
HIF1AN	0.026	0.006	-10000	0	-10000	0	0
GNB2L1	0.027	0.003	-10000	0	-10000	0	0
HIF1A/ARNT	0.011	0.063	-10000	0	-0.26	18	18
CUL2	0.027	0.001	-10000	0	-10000	0	0
OS9	0.027	0.002	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.047	0.021	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.016	0.059	-10000	0	-0.26	17	17
PHD1-3/OS9	0.059	0.035	-10000	0	-0.21	4	4
HIF1A/RACK1/Elongin B/Elongin C	0.03	0.066	-10000	0	-0.29	5	5
VHL	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
HIF1A/JAB1	0.011	0.061	-10000	0	-0.26	17	17
EGLN3	0.023	0.035	-10000	0	-0.4	3	3
EGLN2	0.026	0.02	-10000	0	-0.4	1	1
EGLN1	0.027	0.005	-10000	0	-10000	0	0
TP53	0.022	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.03	0.074	-10000	0	-0.51	7	7
ARNT	0.026	0.02	-10000	0	-0.4	1	1
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.025	0.021	-10000	0	-0.4	1	1
HIF1A/p19ARF	-0.033	0.11	0.22	1	-0.3	23	24

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.055	0.054	-10000	0	-0.58	1	1
epithelial cell differentiation	0.046	0.077	-10000	0	-0.63	1	1
ITCH	0.018	0.015	-10000	0	-10000	0	0
WWP1	0.013	0.067	-10000	0	-1.2	1	1
FYN	0.027	0.004	-10000	0	-10000	0	0
EGFR	0.024	0.021	-10000	0	-0.4	1	1
PRL	-0.008	0.073	-10000	0	-0.43	12	12
neuron projection morphogenesis	0.024	0.085	0.29	11	-0.43	1	12
PTPRZ1	-0.12	0.19	-10000	0	-0.4	146	146
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.031	0.08	-10000	0	-0.46	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.071	-10000	0	-0.51	1	1
ADAM17	0.024	0.011	-10000	0	-10000	0	0
ErbB4/ErbB4	0.015	0.039	-10000	0	-0.64	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.053	0.052	-10000	0	-0.59	1	1
NCOR1	0.022	0.011	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.018	0.075	-10000	0	-0.49	1	1
GRIN2B	-0.037	0.11	0.26	3	-0.38	8	11
ErbB4/ErbB2/betacellulin	0.052	0.048	0.28	1	-0.49	1	2
STAT1	0.026	0.021	-10000	0	-0.43	1	1
HBEGF	0.025	0.03	-10000	0	-0.43	2	2
PRLR	0.018	0.059	-10000	0	-0.4	9	9
E4ICDs/ETO2	0.034	0.085	-10000	0	-0.58	1	1
axon guidance	0.04	0.085	0.31	5	-0.72	1	6
NEDD4	0.021	0.012	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.02	0.07	-10000	0	-0.29	21	21
CBFA2T3	-0.03	0.14	-10000	0	-0.4	61	61
ErbB4/ErbB2/HBEGF	0.053	0.047	0.28	1	-0.49	1	2
MAPK3	0.021	0.081	0.27	8	-0.39	2	10
STAT1 (dimer)	0.057	0.052	-10000	0	-0.58	1	1
MAPK1	0.02	0.08	0.27	8	-0.44	1	9
JAK2	0.024	0.035	-10000	0	-0.4	3	3
ErbB4/ErbB2/neuregulin 1 beta	0.005	0.069	0.24	2	-0.49	1	3
NRG1	-0.024	0.087	-10000	0	-0.28	45	45
NRG3	0.004	0.03	-10000	0	-0.43	1	1
NRG2	-0.04	0.14	-10000	0	-0.4	59	59
NRG4	-0.024	0.12	-10000	0	-0.4	44	44
heart development	0.04	0.085	0.31	5	-0.72	1	6
neural crest cell migration	0.005	0.069	0.24	2	-0.48	1	3
ERBB2	0.01	0.029	0.28	4	-10000	0	4
WWOX/E4ICDs	0.053	0.053	-10000	0	-0.58	1	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.037	0.082	-10000	0	-0.55	1	1
apoptosis	-0.039	0.077	0.38	7	-10000	0	7
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.033	0.082	-10000	0	-0.59	1	1
ErbB4/ErbB2/epiregulin	-0.033	0.12	0.31	3	-0.33	5	8
ErbB4/ErbB4/betacellulin/betacellulin	0.054	0.055	-10000	0	-0.58	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.069	0.078	-10000	0	-0.52	1	1
MDM2	0.011	0.036	0.25	1	-0.58	1	2
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.002	0.061	-10000	0	-0.4	1	1
STAT5A	0.048	0.086	0.37	3	-0.7	1	4
ErbB4/EGFR/neuregulin 1 beta	0.016	0.073	-10000	0	-0.49	1	1
DLG4	0.022	0.024	-10000	0	-0.43	1	1
GRB2/SHC	0.039	0.009	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.041	0.046	-10000	0	-0.55	1	1
STAT5A (dimer)	0.073	0.096	0.32	2	-0.69	1	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.076	0.087	0.34	2	-0.7	1	3
LRIG1	0.027	0.003	-10000	0	-10000	0	0
EREG	-0.16	0.23	0.36	2	-0.43	183	185
BTC	0.023	0.04	-10000	0	-0.4	4	4
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.025	0.073	0.37	1	-0.73	1	2
ERBB4	0.011	0.033	-10000	0	-0.64	1	1
STAT5B	0.027	0.004	-10000	0	-10000	0	0
YAP1	0.012	0.053	-10000	0	-0.44	5	5
GRB2	0.027	0.004	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.032	0.075	0.28	1	-0.49	1	2
glial cell differentiation	-0.041	0.046	0.54	1	-10000	0	1
WWOX	0.024	0.009	-10000	0	-10000	0	0
cell proliferation	0.02	0.096	0.32	6	-0.53	1	7

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.026	0.02	-9999	-0.4	1	1
SPHK1	-0.005	0.12	-9999	-0.43	32	32
GNAI2	0.027	0.004	-9999	-10000	0	0
mol:S1P	0.006	0.034	-9999	-0.24	1	1
GNAO1	-0.088	0.19	-9999	-0.4	122	122
mol:Sphinganine-1-P	-0.01	0.083	-9999	-0.3	33	33
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.042	0.046	-9999	-10000	0	0
GNAI3	0.026	0.005	-9999	-10000	0	0
G12/G13	0.036	0.013	-9999	-10000	0	0
S1PR3	0.026	0.022	-9999	-0.43	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	-0.21	1	1
S1PR5	0.02	0.056	-9999	-0.43	7	7
S1PR4	0.017	0.062	-9999	-0.4	10	10
GNAI1	0.014	0.071	-9999	-0.4	13	13
S1P/S1P5/G12	0.028	0.054	-9999	-0.25	7	7
S1P/S1P3/Gq	0.024	0.055	-9999	-0.36	6	6
S1P/S1P4/Gi	-0.049	0.14	-9999	-0.37	39	39
GNAQ	0.026	0.02	-9999	-0.4	1	1
GNAZ	0.021	0.045	-9999	-0.4	5	5
GNA14	0.025	0.028	-9999	-0.4	2	2
GNA15	0.022	0.048	-9999	-0.43	5	5
GNA12	0.025	0.008	-9999	-10000	0	0
GNA13	0.027	0.005	-9999	-10000	0	0
GNA11	0.025	0.028	-9999	-0.4	2	2
ABCC1	0.027	0.003	-9999	-10000	0	0

×

FoxO family signaling

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
G6PC	-0.12	0.4	-10000	0	-1.2	55	55
PLK1	0.017	0.13	-10000	0	-0.62	6	6
CDKN1B	0.045	0.12	0.3	1	-0.36	7	8
FOXO3	0.026	0.13	-10000	0	-0.64	7	7
KAT2B	0.015	0.083	-10000	0	-0.39	17	17
FOXO1/SIRT1	-0.004	0.15	-10000	0	-0.37	54	54
CAT	0.019	0.13	-10000	0	-0.68	4	4
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.019	0.034	-10000	0	-10000	0	0
FOXO1	-0.017	0.16	-10000	0	-0.4	54	54
MAPK10	0.005	0.089	0.19	33	-0.21	7	40
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.032	0.077	-10000	0	-10000	0	0
response to oxidative stress	0	0.022	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.04	0.12	-10000	0	-0.54	8	8
XPO1	0.028	0.001	-10000	0	-10000	0	0
EP300	0.015	0.033	-10000	0	-10000	0	0
BCL2L11	0.031	0.025	-10000	0	-10000	0	0
FOXO1/SKP2	-0.004	0.15	-10000	0	-0.38	51	51
mol:GDP	0	0.022	-10000	0	-10000	0	0
RAN	0.028	0.002	-10000	0	-10000	0	0
GADD45A	0.038	0.14	-10000	0	-0.61	13	13
YWHAQ	0.027	0.002	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.034	0.12	0.22	2	-0.41	16	18
MST1	-0.039	0.16	-10000	0	-0.42	69	69
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.026	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.008	0.11	-10000	0	-0.41	20	20
YWHAB	0.016	0.014	-10000	0	-10000	0	0
MAPK8	0.035	0.052	0.19	36	-10000	0	36
MAPK9	0.034	0.052	0.19	40	-10000	0	40
YWHAG	0.026	0.005	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
SIRT1	0.029	0.015	-10000	0	-10000	0	0
SOD2	0.04	0.12	-10000	0	-0.5	1	1
RBL2	0.041	0.12	-10000	0	-0.69	3	3
RAL/GDP	0.033	0.026	-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	0.026	0.02	-10000	0	-0.4	1	1
RAL/GTP	0.037	0.025	-10000	0	-10000	0	0
CSNK1G1	0.025	0.021	-10000	0	-0.4	1	1
FASLG	-0.049	0.32	-10000	0	-1.3	29	29
SKP2	0.027	0.004	-10000	0	-10000	0	0
USP7	0.028	0.003	-10000	0	-10000	0	0
IKBKB	0.028	0.018	-10000	0	-10000	0	0
CCNB1	0.019	0.13	-10000	0	-0.68	4	4
FOXO1-3a-4/beta catenin	0.051	0.12	0.28	11	-10000	0	11
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.15	-10000	0	-0.37	51	51
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
SGK1	0.012	0.089	-10000	0	-0.39	20	20
CSNK1G3	0.027	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.041	0.004	-10000	0	-10000	0	0
ZFAND5	0.031	0.072	0.36	1	-10000	0	1
SFN	0.023	0.029	-10000	0	-0.4	2	2
CDK2	0.012	0.043	-10000	0	-10000	0	0
FOXO3A/14-3-3	0	0.1	-10000	0	-0.42	14	14
CREBBP	0.011	0.044	-10000	0	-0.2	1	1
FBXO32	0.046	0.16	0.38	1	-0.71	6	7
BCL6	0.041	0.11	-10000	0	-0.72	2	2
RALB	0.028	0.001	-10000	0	-10000	0	0
RALA	0.026	0.008	-10000	0	-10000	0	0
YWHAH	0.026	0.006	-10000	0	-10000	0	0

×

Class I PI3K 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
ARF5/GTP	-0.004	0.049	-10000	0	-10000	0	0
DAPP1	-0.017	0.15	0.22	21	-0.39	31	52
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.069	0.2	0.24	12	-0.52	45	57
mol:DAG	-0.006	0.095	0.18	50	-0.24	14	64
HRAS	0.026	0.021	-10000	0	-0.4	1	1
RAP1A	0.027	0.008	-10000	0	-10000	0	0
ARF5/GDP	0.028	0.12	0.18	3	-0.41	18	21
PLCG2	-0.015	0.13	-10000	0	-0.4	45	45
PLCG1	0.016	0.013	-10000	0	-10000	0	0
ARF5	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	-0.014	0.026	-10000	0	-10000	0	0
ARF1/GTP	0.004	0.039	0.24	1	-10000	0	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
YES1	0.022	0.022	-10000	0	-0.4	1	1
RAP1A/GTP	-0.014	0.027	-10000	0	-10000	0	0
ADAP1	-0.014	0.029	-10000	0	-0.36	1	1
ARAP3	-0.014	0.026	-10000	0	-10000	0	0
INPPL1	0.027	0.004	-10000	0	-10000	0	0
PREX1	0.015	0.024	-10000	0	-0.4	1	1
ARHGEF6	0.017	0.065	-10000	0	-0.4	11	11
ARHGEF7	0.021	0.012	-10000	0	-10000	0	0
ARF1	0.027	0.005	-10000	0	-10000	0	0
NRAS	0.025	0.029	-10000	0	-0.4	2	2
FYN	0.027	0.004	-10000	0	-10000	0	0
ARF6	0.025	0.007	-10000	0	-10000	0	0
FGR	0.022	0.041	-10000	0	-0.4	4	4
mol:Ca2+	0.002	0.058	0.16	5	-10000	0	5
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.012	0.12	-10000	0	-0.4	41	41
ZAP70	0.015	0.071	-10000	0	-0.4	13	13
mol:IP3	-0.004	0.073	0.17	17	-0.2	2	19
LYN	0.024	0.009	-10000	0	-10000	0	0
ARF1/GDP	0.028	0.12	0.18	3	-0.42	18	21
RhoA/GDP	0.039	0.07	0.23	4	-0.3	3	7
PDK1/Src/Hsp90	0.033	0.028	-10000	0	-10000	0	0
BLNK	0.022	0.045	-10000	0	-0.4	5	5
actin cytoskeleton reorganization	0.035	0.095	0.22	26	-0.36	7	33
SRC	0.017	0.013	-10000	0	-10000	0	0
PLEKHA2	-0.007	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PTEN	0.026	0.009	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
ARF6/GTP	-0.014	0.032	-10000	0	-10000	0	0
RhoA/GTP	-0.014	0.027	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.035	0.11	-10000	0	-0.39	20	20
BLK	-0.1	0.19	-10000	0	-0.4	129	129
PDPK1	0.027	0.003	-10000	0	-10000	0	0
CYTH1	-0.015	0.026	-10000	0	-10000	0	0
HCK	0.01	0.053	-10000	0	-0.4	7	7
CYTH3	-0.014	0.025	-10000	0	-10000	0	0
CYTH2	-0.015	0.026	-10000	0	-10000	0	0
KRAS	0.027	0.006	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.006	0.08	-10000	0	-0.38	18	18
SGK1	-0.005	0.088	-10000	0	-0.4	18	18
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
mol:GDP	0.017	0.12	0.18	5	-0.43	19	24
SOS1	0.027	0.002	-10000	0	-10000	0	0
SYK	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.024	0.066	0.22	4	-0.3	3	7
mol:PI-3-4-5-P3	-0.014	0.026	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	-0.014	0.027	-10000	0	-10000	0	0
VAV1	0.007	0.089	-10000	0	-0.4	21	21
mol:PI-3-4-P2	0.013	0.014	-10000	0	-0.28	1	1
RAS family/GTP/PI3K Class I	0.044	0.04	-10000	0	-10000	0	0
PLEKHA1	-0.009	0.011	-10000	0	-0.24	1	1
Rac1/GDP	0.021	0.12	0.18	3	-0.43	17	20
LAT	0.024	0.035	-10000	0	-0.41	3	3
Rac1/GTP	-0.017	0.11	-10000	0	-0.39	29	29
ITK	-0.023	0.041	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.016	0.12	0.2	47	-0.32	21	68
LCK	0.017	0.063	-10000	0	-0.42	9	9
BTK	-0.037	0.064	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0.016	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.011	0.006	-10000	0	-10000	0	0
mol:DAG	0.015	0.057	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.023	0.017	0.23	1	-10000	0	1
CaM/Ca2+	0.024	0.057	-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	0.039	0.073	-10000	0	-10000	0	0
PLCG1	0.015	0.057	-10000	0	-10000	0	0
NOS3	0.08	0.11	0.29	61	-10000	0	61
CBL	0.027	0.004	-10000	0	-10000	0	0
mol:NO	0.079	0.11	0.29	62	-0.4	1	63
FLT1	0.014	0.009	-10000	0	-10000	0	0
PGF	0.011	0.079	-10000	0	-0.43	14	14
VEGFR1 homodimer/NRP2/VEGFR121	0.035	0.032	0.25	1	-10000	0	1
CALM1	0.025	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
eNOS/Hsp90	0.091	0.11	0.29	62	-0.37	1	63
endothelial cell proliferation	0.046	0.12	0.33	42	-10000	0	42
mol:Ca2+	0.015	0.057	-10000	0	-10000	0	0
MAPK3	0.002	0.054	-10000	0	-10000	0	0
MAPK1	0.002	0.052	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
PLGF homodimer	0.011	0.079	-10000	0	-0.43	14	14
PRKACA	0.027	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.023	0.04	-10000	0	-0.4	4	4
VEGFA homodimer	0.028	0.016	0.36	1	-10000	0	1
VEGFR1 homodimer/VEGFA homodimer	0.026	0.019	0.25	1	-10000	0	1
platelet activating factor biosynthetic process	0.07	0.13	0.34	55	-10000	0	55
PI3K	0.04	0.05	-10000	0	-10000	0	0
PRKCA	0.004	0.056	0.19	27	-10000	0	27
PRKCB	-0.015	0.075	0.19	21	-10000	0	21
VEGFR1 homodimer/PLGF homodimer	0.019	0.047	-10000	0	-0.25	11	11
VEGFA	0.028	0.016	0.36	1	-10000	0	1
VEGFB	0.027	0.004	-10000	0	-10000	0	0
mol:IP3	0.015	0.057	-10000	0	-10000	0	0
RASA1	0.049	0.072	-10000	0	-10000	0	0
NRP2	0.025	0.034	-10000	0	-0.4	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	0.027	0.002	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.085	0.11	0.29	55	-0.39	1	56
PTPN11	0.027	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.038	0.049	-10000	0	-10000	0	0
mol:L-citrulline	0.079	0.11	0.29	62	-0.4	1	63
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.042	0.046	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.037	0.025	0.25	1	-10000	0	1
CD2AP	0.016	0.068	-10000	0	-0.4	12	12
PI3K/GAB1	0.08	0.068	-10000	0	-10000	0	0
PDPK1	0.041	0.078	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.037	0.025	0.25	1	-10000	0	1
mol:NADP	0.079	0.11	0.29	62	-0.4	1	63
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.04	0.045	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.024	0.026	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.007	0.05	-10000	0	-0.4	2	2
SVIL	0.012	0.036	-10000	0	-10000	0	0
ZNF318	0.049	0.056	0.19	12	-10000	0	12
JMJD2C	0.004	0.019	-10000	0	-0.071	19	19
T-DHT/AR/Ubc9	0.024	0.067	-10000	0	-0.23	26	26
CARM1	0.019	0.019	-10000	0	-10000	0	0
PRDX1	0.029	0.007	-10000	0	-10000	0	0
PELP1	0.026	0.015	-10000	0	-10000	0	0
CTNNB1	0.013	0.033	-10000	0	-10000	0	0
AKT1	0.032	0.019	-10000	0	-10000	0	0
PTK2B	0.012	0.032	-10000	0	-0.4	1	1
MED1	0.035	0.026	0.36	1	-10000	0	1
MAK	0.033	0.1	0.36	1	-0.42	15	16
response to oxidative stress	0.002	0.005	-10000	0	-10000	0	0
HIP1	0.011	0.041	-10000	0	-0.4	1	1
GSN	0.001	0.076	-10000	0	-0.42	10	10
NCOA2	0.017	0.026	-10000	0	-0.4	1	1
NCOA6	0.01	0.027	-10000	0	-10000	0	0
DNA-PK	0.061	0.053	-10000	0	-10000	0	0
NCOA4	0.024	0.022	-10000	0	-0.4	1	1
PIAS3	0.013	0.033	-10000	0	-10000	0	0
cell proliferation	0.028	0.071	0.27	1	-0.38	4	5
XRCC5	0.033	0.013	-10000	0	-10000	0	0
UBE3A	0.007	0.05	-10000	0	-0.4	1	1
T-DHT/AR/SNURF	-0.002	0.1	-10000	0	-0.25	58	58
FHL2	0.044	0.054	-10000	0	-10000	0	0
RANBP9	0.009	0.045	-10000	0	-0.4	1	1
JMJD1A	0.002	0.011	-10000	0	-0.13	2	2
CDK6	0.027	0.007	-10000	0	-10000	0	0
TGFB1I1	0.012	0.036	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.008	0.074	-10000	0	-0.24	29	29
XRCC6	0.031	0.015	-10000	0	-10000	0	0
T-DHT/AR	0.032	0.074	-10000	0	-0.23	26	26
CTDSP1	0.018	0.023	-10000	0	-10000	0	0
CTDSP2	0.043	0.038	-10000	0	-10000	0	0
BRCA1	0.013	0.035	-10000	0	-10000	0	0
TCF4	0.027	0.034	-10000	0	-0.4	1	1
CDKN2A	-0.062	0.19	0.36	2	-0.42	97	99
SRF	0.04	0.021	-10000	0	-10000	0	0
NKX3-1	-0.002	0.031	-10000	0	-0.16	6	6
KLK3	-0.19	0.48	-10000	0	-1.3	71	71
TMF1	0.018	0.027	-10000	0	-0.4	1	1
HNRNPA1	0.036	0.022	-10000	0	-10000	0	0
AOF2	-0.012	0.029	-10000	0	-0.079	71	71
APPL1	0.024	0.041	-10000	0	-0.28	2	2
T-DHT/AR/Caspase 8	0.033	0.073	-10000	0	-0.23	26	26
AR	0.001	0.1	-10000	0	-0.4	26	26
UBA3	0.017	0.023	-10000	0	-10000	0	0
PATZ1	0.034	0.022	-10000	0	-10000	0	0
PAWR	0.019	0.019	-10000	0	-10000	0	0
PRKDC	0.028	0.015	-10000	0	-10000	0	0
PA2G4	0.037	0.024	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.029	0.065	-10000	0	-0.21	26	26
RPS6KA3	0.009	0.043	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.017	0.068	-10000	0	-0.23	27	27
LATS2	0.028	0.024	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.035	0.072	0.17	3	-0.21	23	26
Cyclin D3/CDK11 p58	0.022	0.005	-10000	0	-10000	0	0
VAV3	-0.027	0.13	-10000	0	-0.4	44	44
KLK2	0.002	0.066	-10000	0	-0.37	2	2
CASP8	0.031	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.021	0.068	-10000	0	-0.22	23	23
TMPRSS2	0.009	0.062	-10000	0	-0.82	2	2
CCND1	0.013	0.044	-10000	0	-0.43	3	3
PIAS1	0.007	0.048	-10000	0	-10000	0	0
mol:T-DHT	0.002	0.009	-10000	0	-0.061	3	3
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.001	0.069	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.026	0.069	-10000	0	-0.23	26	26
CMTM2	0.01	0.09	-10000	0	-0.42	18	18
SNURF	-0.019	0.12	-10000	0	-0.4	37	37
ZMIZ1	0.027	0.016	-10000	0	-10000	0	0
CCND3	0.028	0.004	-10000	0	-10000	0	0
TGIF1	0.029	0.023	-10000	0	-10000	0	0
FKBP4	0.01	0.045	0.36	1	-10000	0	1

×

Class I PI3K signaling events mediated by Akt

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	0.008	0.007	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0.026	-10000	0	-0.21	1	1
CDKN1B	0.023	0.064	-10000	0	-0.32	9	9
CDKN1A	0.022	0.067	-10000	0	-0.31	11	11
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.024	0.009	-10000	0	-10000	0	0
FOXO3	0.024	0.057	-10000	0	-0.28	8	8
AKT1	0.002	0.059	-10000	0	-0.32	11	11
BAD	0.026	0.02	-10000	0	-0.4	1	1
AKT3	0.01	0.036	-10000	0	-0.27	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.024	0.064	-10000	0	-0.32	9	9
AKT1/ASK1	0.041	0.092	-10000	0	-0.32	10	10
BAD/YWHAZ	0.045	0.025	-10000	0	-0.24	1	1
RICTOR	0.023	0.04	-10000	0	-0.4	4	4
RAF1	0.027	0.003	-10000	0	-10000	0	0
JNK cascade	-0.037	0.088	0.31	10	-10000	0	10
TSC1	0.022	0.067	-10000	0	-0.31	11	11
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
AKT1/RAF1	0.044	0.095	-10000	0	-0.32	12	12
EP300	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.025	0.069	-10000	0	-0.32	11	11
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.023	0.064	-10000	0	-0.32	9	9
YWHAQ	0.027	0.002	-10000	0	-10000	0	0
TBC1D4	0.057	0.095	0.24	97	-10000	0	97
MAP3K5	0.027	0.004	-10000	0	-10000	0	0
MAPKAP1	0.027	0.003	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.051	0.094	0.29	8	-0.2	47	55
YWHAH	0.026	0.006	-10000	0	-10000	0	0
AKT1S1	0.023	0.066	-10000	0	-0.31	10	10
CASP9	0.024	0.058	-10000	0	-0.32	7	7
YWHAB	0.016	0.014	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.043	0.093	0.26	2	-0.51	2	4
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.033	0.028	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
SRC	0.017	0.013	-10000	0	-10000	0	0
AKT2/p21CIP1	0.02	0.076	0.23	2	-0.4	4	6
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.03	-10000	0	-0.24	1	1
CHUK	0.025	0.053	-10000	0	-0.28	7	7
BAD/BCL-XL	0.017	0.065	-10000	0	-0.43	2	2
mTORC2	0.032	0.024	-10000	0	-0.21	4	4
AKT2	0.014	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.06	0.12	0.26	46	-0.4	9	55
PDPK1	0.027	0.003	-10000	0	-10000	0	0
MDM2	0.023	0.066	-10000	0	-0.31	10	10
MAPKKK cascade	-0.044	0.093	0.32	12	-10000	0	12
MDM2/Cbp/p300	0.05	0.091	-10000	0	-0.49	2	2
TSC1/TSC2	0.021	0.063	0.34	1	-0.59	1	2
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.087	-10000	0	-0.46	2	2
glucose import	0.014	0.097	0.21	64	-0.2	39	103
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.024	0.047	0.18	4	-0.34	1	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.014	0.097	0.21	64	-0.2	39	103
GSK3A	0.024	0.065	-10000	0	-0.31	10	10
FOXO1	0.024	0.071	0.22	1	-0.32	8	9
GSK3B	0.023	0.068	-10000	0	-0.31	11	11
SFN	0.023	0.029	-10000	0	-0.4	2	2
G1/S transition of mitotic cell cycle	0.034	0.078	0.26	3	-0.52	2	5
p27Kip1/14-3-3 family	0.045	0.052	0.21	1	-10000	0	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
KPNA1	0.027	0.002	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
YWHAG	0.026	0.005	-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 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
EEF2K	-0.007	0.003	-10000	0	-10000	0	0
SNTA1	0.016	0.024	-10000	0	-0.4	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.007	0.011	-10000	0	-0.24	1	1
MAPK12	-0.007	0.037	-10000	0	-0.27	8	8
CCND1	0.007	0.038	-10000	0	-0.32	4	4
p38 gamma/SNTA1	0.008	0.043	0.19	4	-0.24	9	13
MAP2K3	0.023	0.01	-10000	0	-10000	0	0
PKN1	0.027	0.003	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.004	0.044	0.2	6	-0.26	8	14
MAP2K6	0.001	0.021	-10000	0	-0.22	4	4
MAPT	-0.055	0.12	0.18	7	-0.28	93	100
MAPK13	0.012	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

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC3	0.027	0.004	-10000	0	-10000	0	0
VDR	0.027	0.003	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.041	0.056	-10000	0	-0.23	17	17
EP300	0.026	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.004	0.039	-10000	0	-0.32	1	1
KAT2B	0.011	0.081	-10000	0	-0.4	17	17
MAPK14	0.027	0.003	-10000	0	-10000	0	0
AKT1	-0.002	0.047	0.19	1	-0.2	4	5
RAR alpha/9cRA/Cyclin H	0.012	0.069	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.007	0.054	0.18	1	-0.23	10	11
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.002	0.054	-10000	0	-0.25	2	2
NCOR2	0.026	0.02	-10000	0	-0.4	1	1
VDR/VDR/Vit D3	0.02	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.027	0.082	0.3	1	-0.45	5	6
NCOA2	0.023	0.022	-10000	0	-0.4	1	1
NCOA3	0.016	0.014	-10000	0	-10000	0	0
NCOA1	0.027	0.001	-10000	0	-10000	0	0
VDR/VDR/DNA	0.027	0.003	-10000	0	-10000	0	0
RARG	0.028	0.004	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.037	0.006	-10000	0	-10000	0	0
MAPK3	0.026	0.02	-10000	0	-0.4	1	1
MAPK1	0.026	0.006	-10000	0	-10000	0	0
MAPK8	0.027	0.006	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.027	0.081	0.26	1	-0.37	5	6
RARA	-0.012	0.055	0.18	3	-0.21	7	10
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.004	0.05	0.18	1	-0.22	9	10
PRKCA	0.028	0.009	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.033	0.086	0.32	1	-0.45	5	6
RXRG	-0.14	0.16	0.28	3	-0.32	165	168
RXRA	-0.008	0.055	0.26	1	-10000	0	1
RXRB	-0.027	0.082	0.27	4	-0.34	3	7
VDR/Vit D3/DNA	0.02	0.002	-10000	0	-10000	0	0
RBP1	0.001	0.11	0.36	1	-0.43	27	28
CRBP1/9-cic-RA	0.002	0.077	0.24	1	-0.3	27	28
RARB	0.024	0.04	-10000	0	-0.4	4	4
PRKCG	-0.12	0.22	0.36	4	-0.42	147	151
MNAT1	0.024	0.022	-10000	0	-0.43	1	1
RAR alpha/RXRs	-0.027	0.077	-10000	0	-0.4	6	6
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.019	0.072	0.3	1	-0.37	3	4
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.073	0.24	4	-0.27	3	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.032	0.086	0.32	1	-0.45	5	6
positive regulation of DNA binding	0.005	0.061	-10000	0	-10000	0	0
NRIP1	-0.033	0.1	-10000	0	-1.1	2	2
RXRs/RARs	-0.031	0.086	0.34	1	-0.38	6	7
RXRs/RXRs/DNA/9cRA	-0.037	0.072	-10000	0	-0.36	6	6
PRKACA	0.027	0.003	-10000	0	-10000	0	0
CDK7	0.027	0.005	-10000	0	-10000	0	0
TFIIH	0.05	0.022	-10000	0	-0.26	1	1
RAR alpha/9cRA	0.02	0.066	0.23	1	-0.25	2	3
CCNH	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.027	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.048	0.022	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.1	0.18	-10000	0	-0.4	79	79
CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
AKT1	0.025	0.007	-10000	0	-10000	0	0
AKT2	0.027	0.004	-10000	0	-10000	0	0
STXBP4	0.026	0.02	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.12	0.18	-10000	0	-0.42	86	86
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
CALM1	0.025	0.007	-10000	0	-10000	0	0
YWHAQ	0.027	0.002	-10000	0	-10000	0	0
TBC1D4	0.01	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.026	0.006	-10000	0	-10000	0	0
YWHAB	0.016	0.014	-10000	0	-10000	0	0
SNARE/Synip	0.044	0.026	-10000	0	-0.24	1	1
YWHAG	0.026	0.005	-10000	0	-10000	0	0
ASIP	0.003	0.041	0.36	2	-0.43	2	4
PRKCI	0.025	0.028	-10000	0	-0.4	2	2
AS160/CaM/Ca2+	0.019	0.005	-10000	0	-10000	0	0
RHOQ	0.027	0.003	-10000	0	-10000	0	0
GYS1	0.011	0.004	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
TRIP10	0.027	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.006	-10000	0	-10000	0	0
AS160/14-3-3	0.014	0.041	-10000	0	-0.25	3	3
VAMP2	0.023	0.011	-10000	0	-10000	0	0
SLC2A4	-0.14	0.2	-10000	0	-0.48	86	86
STX4	0.027	0.003	-10000	0	-10000	0	0
GSK3B	0.02	0.007	-10000	0	-10000	0	0
SFN	0.023	0.029	-10000	0	-0.4	2	2
LNPEP	0.026	0.007	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.017	0.013	-10000	0	-10000	0	0
NFATC1	-0.015	0.12	0.25	1	-0.39	29	30
NFATC2	0.033	0.052	0.14	2	-0.23	3	5
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	-0.053	0.11	-10000	0	-0.28	53	53
Exportin 1/Ran/NUP214	0.055	0.008	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.036	0.12	-10000	0	-0.35	27	27
BCL2/BAX	0.024	0.047	-10000	0	-0.28	9	9
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	0.003	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
BAD	0.026	0.02	-10000	0	-0.4	1	1
CABIN1/MEF2D	-0.041	0.11	-10000	0	-0.35	20	20
Calcineurin A alpha-beta B1/BCL2	0.012	0.059	-10000	0	-0.4	9	9
FKBP8	0.026	0.02	-10000	0	-0.4	1	1
activation-induced cell death of T cells	0.04	0.11	0.34	20	-10000	0	20
KPNB1	0.027	0.004	-10000	0	-10000	0	0
KPNA2	0.028	0.016	0.36	1	-10000	0	1
XPO1	0.027	0.001	-10000	0	-10000	0	0
SFN	0.023	0.029	-10000	0	-0.4	2	2
MAP3K8	0.027	0.002	-10000	0	-10000	0	0
NFAT4/CK1 alpha	0.027	0.024	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.07	0.067	-10000	0	-0.32	1	1
CABIN1	-0.053	0.11	-10000	0	-0.28	53	53
CALM1	0.026	0.007	-10000	0	-10000	0	0
RAN	0.027	0.002	-10000	0	-10000	0	0
MAP3K1	0.026	0.02	-10000	0	-0.4	1	1
CAMK4	0.002	0.097	-10000	0	-0.4	25	25
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.026	0.02	-10000	0	-0.4	1	1
YWHAH	0.026	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.025	0.063	-10000	0	-0.28	18	18
YWHAB	0.016	0.014	-10000	0	-10000	0	0
MAPK8	0.027	0.004	-10000	0	-10000	0	0
MAPK9	0.027	0.003	-10000	0	-10000	0	0
YWHAG	0.026	0.005	-10000	0	-10000	0	0
FKBP1A	0.022	0.011	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.014	0.13	0.22	1	-0.4	16	17
PRKCH	0.025	0.021	-10000	0	-0.4	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	0.015	0.007	-10000	0	-10000	0	0
apoptosis	0.01	0.016	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.031	0.045	-10000	0	-0.36	1	1
PRKCB	-0.068	0.18	-10000	0	-0.4	101	101
PRKCE	0.027	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	0.024	0.039	-10000	0	-10000	0	0
BAD/BCL-XL	0.024	0.025	-10000	0	-0.28	1	1
PRKCD	0.027	0.004	-10000	0	-10000	0	0
NUP214	0.027	0.003	-10000	0	-10000	0	0
PRKCZ	0.026	0.007	-10000	0	-10000	0	0
PRKCA	0.026	0.006	-10000	0	-10000	0	0
PRKCG	-0.12	0.22	0.36	4	-0.43	147	151
PRKCQ	0.023	0.04	-10000	0	-0.4	4	4
FKBP38/BCL2	0.024	0.049	-10000	0	-0.28	10	10
EP300	0.026	0.008	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.022	0.011	-10000	0	-10000	0	0
NFATc/JNK1	-0.001	0.12	0.25	1	-0.37	27	28
CaM/Ca2+/FKBP38	0.034	0.017	-10000	0	-0.24	1	1
FKBP12/FK506	0.017	0.008	-10000	0	-10000	0	0
CSNK1A1	0.014	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.018	0.061	-10000	0	-0.23	25	25
NFATc/ERK1	-0.002	0.12	0.25	1	-0.37	28	29
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.039	0.12	-10000	0	-0.35	29	29
NR4A1	0.039	0.073	0.23	3	-0.37	8	11
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	0.038	-10000	0	-10000	0	0
RCH1/ KPNB1	0.04	0.007	-10000	0	-10000	0	0
YWHAQ	0.027	0.002	-10000	0	-10000	0	0
PRKACA	0.027	0.004	-10000	0	-10000	0	0
AKAP5	0.008	0.083	-10000	0	-0.4	18	18
MEF2D	0.027	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.002	0.13	0.25	1	-0.37	28	29
CREBBP	0.027	0.007	-10000	0	-10000	0	0
BCL2	0.012	0.059	-10000	0	-0.4	9	9

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.02	0.13	-10000	0	-0.4	45	45
CLTC	-0.005	0.11	-10000	0	-0.4	30	30
calcium ion-dependent exocytosis	0.012	0.046	-10000	0	-10000	0	0
Dynamin 2/GTP	0.021	0.037	0.19	1	-0.23	9	10
EXOC4	0.027	0.005	-10000	0	-10000	0	0
CD59	0.001	0.078	-10000	0	-0.31	23	23
CPE	-0.004	0.062	-10000	0	-0.23	30	30
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
membrane fusion	0.019	0.03	-10000	0	-10000	0	0
CTNND1	0.01	0.04	0.18	9	-0.21	9	18
DNM2	0.027	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.002	0.069	-10000	0	-0.32	10	10
TSHR	0.003	0.032	-10000	0	-0.23	7	7
INS	0.006	0.045	-10000	0	-0.48	3	3
BIN1	0.026	0.02	-10000	0	-0.4	1	1
mol:Choline	0.019	0.03	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.038	0.23	1	-0.25	9	10
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.025	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.02	0.037	0.18	1	-0.22	9	10
JUP	0.001	0.078	0.21	1	-0.31	23	24
ASAP2/amphiphysin II	0.048	0.019	-10000	0	-0.21	1	1
ARF6/GTP	0.019	0.005	-10000	0	-10000	0	0
CDH1	0.001	0.076	-10000	0	-0.31	23	23
clathrin-independent pinocytosis	0.019	0.005	-10000	0	-10000	0	0
MAPK8IP3	0.025	0.029	-10000	0	-0.41	2	2
positive regulation of endocytosis	0.019	0.005	-10000	0	-10000	0	0
EXOC2	0.026	0.02	-10000	0	-0.4	1	1
substrate adhesion-dependent cell spreading	0.025	0.045	-10000	0	-0.4	3	3
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	-0.018	0.097	0.33	26	-10000	0	26
positive regulation of phagocytosis	0.013	0.005	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.033	0.021	-10000	0	-0.24	2	2
ACAP1	0.019	0.033	-10000	0	-0.28	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.039	0.11	-10000	0	-0.39	25	25
clathrin heavy chain/ACAP1	-0.001	0.095	0.19	1	-0.33	28	29
JIP4/KLC1	0.047	0.017	-10000	0	-10000	0	0
EXOC1	0.026	0.02	-10000	0	-0.4	1	1
exocyst	0.022	0.042	-10000	0	-0.41	3	3
RALA/GTP	0.018	0.006	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.034	0.011	-10000	0	-10000	0	0
receptor recycling	0.019	0.005	-10000	0	-10000	0	0
CTNNA1	0.01	0.04	0.18	9	-0.22	6	15
NME1	0.009	0.039	0.23	1	-0.25	9	10
clathrin coat assembly	-0.004	0.11	-10000	0	-0.39	30	30
IL2RA	-0.001	0.079	-10000	0	-0.31	23	23
VAMP3	0.013	0.005	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.011	0.1	-10000	0	-0.32	25	25
EXOC6	0.026	0.006	-10000	0	-10000	0	0
PLD1	0.012	0.013	-10000	0	-0.24	1	1
PLD2	0.011	0.007	-10000	0	-10000	0	0
EXOC5	0.023	0.035	-10000	0	-0.4	3	3
PIP5K1C	0.007	0.059	-10000	0	-0.23	17	17
SDC1	0.001	0.077	-10000	0	-0.31	23	23
ARF6/GDP	0.018	0.04	0.2	1	-0.25	9	10
EXOC7	0.027	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.02	0.1	-10000	0	-0.34	26	26
mol:Phosphatidic acid	0.019	0.03	-10000	0	-10000	0	0
endocytosis	-0.046	0.019	0.21	1	-10000	0	1
SCAMP2	0.026	0.006	-10000	0	-10000	0	0
ADRB2	-0.033	0.13	-10000	0	-0.44	30	30
EXOC3	0.027	0.004	-10000	0	-10000	0	0
ASAP2	0.027	0.002	-10000	0	-10000	0	0
Dynamin 2/GDP	0.024	0.038	0.21	1	-0.22	9	10
KLC1	0.025	0.007	-10000	0	-10000	0	0
AVPR2	-0.019	0.12	0.24	2	-0.39	30	32
RALA	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.016	0.095	-10000	0	-0.41	7	7

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.028	0.061	0.3	14	-0.24	1	15
KIRREL	0.022	0.047	-10000	0	-0.41	5	5
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.028	0.061	0.24	1	-0.3	14	15
PLCG1	0.016	0.013	-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	0.044	0.075	-10000	0	-0.24	18	18
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.021	0.032	-10000	0	-0.21	3	3
FYN	0.012	0.061	0.27	11	-0.24	4	15
mol:Ca2+	0.028	0.056	-10000	0	-0.23	12	12
mol:DAG	0.029	0.056	-10000	0	-0.23	12	12
NPHS2	0.014	0.045	-10000	0	-0.42	4	4
mol:IP3	0.029	0.056	-10000	0	-0.23	12	12
regulation of endocytosis	0.036	0.05	0.21	1	-0.33	1	2
Nephrin/NEPH1/podocin/Cholesterol	0.036	0.054	0.21	1	-0.23	16	17
establishment of cell polarity	0.028	0.061	0.24	1	-0.3	14	15
Nephrin/NEPH1/podocin/NCK1-2	0.065	0.058	-10000	0	-0.38	1	1
Nephrin/NEPH1/beta Arrestin2	0.038	0.051	0.22	1	-0.34	1	2
NPHS1	0.015	0.068	0.33	1	-0.43	9	10
Nephrin/NEPH1/podocin	0.038	0.049	0.22	1	-0.24	5	6
TJP1	0.026	0.007	-10000	0	-10000	0	0
NCK1	0.027	0.002	-10000	0	-10000	0	0
NCK2	0.027	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.03	0.057	-10000	0	-0.23	12	12
CD2AP	0.016	0.068	-10000	0	-0.4	12	12
Nephrin/NEPH1/podocin/GRB2	0.051	0.059	0.23	1	-0.23	15	16
GRB2	0.027	0.004	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.012	0.078	0.28	9	-0.25	14	23
cytoskeleton organization	0.01	0.042	0.2	5	-0.28	1	6
Nephrin/NEPH1	0.025	0.043	0.2	1	-0.2	14	15
Nephrin/NEPH1/ZO-1	0.04	0.053	0.23	1	-0.23	14	15

×

Arf6 downstream 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
PLAUR	0.016	0.029	-10000	0	-10000	0	0
regulation of axonogenesis	-0.008	0.032	0.23	7	-10000	0	7
myoblast fusion	-0.028	0.019	-10000	0	-10000	0	0
mol:GTP	0.014	0.034	-10000	0	-0.15	2	2
regulation of calcium-dependent cell-cell adhesion	-0.018	0.094	0.25	42	-10000	0	42
ARF1/GTP	0.027	0.037	-10000	0	-10000	0	0
mol:GM1	0.003	0.028	-10000	0	-10000	0	0
mol:Choline	0.008	0.019	-10000	0	-0.22	1	1
lamellipodium assembly	0.001	0.088	-10000	0	-0.34	27	27
MAPK3	0.018	0.028	-10000	0	-0.24	1	1
ARF6/GTP/NME1/Tiam1	0.019	0.095	-10000	0	-0.25	42	42
ARF1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.028	0.019	-10000	0	-10000	0	0
ARF1/GDP	0.022	0.06	-10000	0	-0.24	8	8
ARF6	0.032	0.009	-10000	0	-10000	0	0
RAB11A	0.026	0.006	-10000	0	-10000	0	0
TIAM1	-0.012	0.12	-10000	0	-0.4	41	41
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.024	-10000	0	-10000	0	0
actin filament bundle formation	-0.023	0.06	0.24	8	-10000	0	8
KALRN	0.02	0.018	-10000	0	-0.2	1	1
RAB11FIP3/RAB11A	0.038	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.024	0.061	-10000	0	-0.24	8	8
NME1	0.019	0.066	0.36	1	-0.43	9	10
Rac1/GDP	0.021	0.059	-10000	0	-0.24	7	7
substrate adhesion-dependent cell spreading	0.014	0.034	-10000	0	-0.15	2	2
cortical actin cytoskeleton organization	0.002	0.086	-10000	0	-0.34	25	25
RAC1	0.025	0.008	-10000	0	-10000	0	0
liver development	0.014	0.034	-10000	0	-0.15	2	2
ARF6/GTP	0.014	0.034	-10000	0	-0.15	2	2
RhoA/GTP	0.027	0.037	-10000	0	-10000	0	0
mol:GDP	0.011	0.051	-10000	0	-0.2	18	18
ARF6/GTP/RAB11FIP3/RAB11A	0.042	0.037	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
PLD1	0.012	0.035	-10000	0	-0.25	1	1
RAB11FIP3	0.027	0.004	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.088	-10000	0	-0.34	27	27
ruffle organization	0.008	0.032	-10000	0	-0.23	7	7
regulation of epithelial cell migration	0.014	0.034	-10000	0	-0.15	2	2
PLD2	0.016	0.019	-10000	0	-10000	0	0
PIP5K1A	0.008	0.032	-10000	0	-0.23	7	7
mol:Phosphatidic acid	0.008	0.019	-10000	0	-0.22	1	1
Rac1/GTP	0.002	0.087	-10000	0	-0.34	25	25

×

EPO signaling pathway

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
BCL2L1	0.023	0.062	-10000	0	-10000	0	0
CRKL	0.021	0.049	0.3	1	-0.29	2	3
mol:DAG	0.019	0.031	-10000	0	-10000	0	0
HRAS	0.011	0.056	0.27	2	-10000	0	2
MAPK8	0.038	0.064	0.19	48	-10000	0	48
RAP1A	0.02	0.049	0.3	1	-0.29	2	3
GAB1	0.02	0.049	0.3	1	-0.29	2	3
MAPK14	0.039	0.064	0.19	50	-10000	0	50
EPO	0.02	0.042	0.34	1	-0.43	3	4
PLCG1	0.019	0.031	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.026	0.024	-10000	0	-0.39	1	1
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1
EPO/EPOR (dimer)/SOCS3	0.047	0.038	0.24	1	-0.25	5	6
GAB1/SHC/GRB2/SOS1	0.051	0.051	0.27	1	-0.3	1	2
EPO/EPOR (dimer)	0.034	0.038	0.25	1	-0.3	4	5
IRS2	0.014	0.039	-10000	0	-0.33	1	1
STAT1	0.028	0.05	-10000	0	-10000	0	0
STAT5B	0.027	0.045	-10000	0	-10000	0	0
cell proliferation	0.02	0.075	0.19	67	-10000	0	67
GAB1/SHIP/PIK3R1/SHP2/SHC	0.041	0.045	-10000	0	-0.29	1	1
TEC	0.02	0.05	0.3	1	-0.3	2	3
SOCS3	0.026	0.022	-10000	0	-0.43	1	1
STAT1 (dimer)	0.028	0.05	-10000	0	-10000	0	0
JAK2	0.025	0.037	-10000	0	-0.4	3	3
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.065	0.053	0.25	1	-0.3	2	3
EPO/EPOR	0.034	0.038	0.25	1	-0.3	4	5
LYN	0.023	0.013	-10000	0	-10000	0	0
TEC/VAV2	0.031	0.055	0.28	1	-0.25	1	2
elevation of cytosolic calcium ion concentration	0.026	0.024	-10000	0	-0.39	1	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.045	0.038	0.24	1	-0.23	3	4
mol:IP3	0.019	0.031	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.035	0.046	-10000	0	-0.31	1	1
SH2B3	0.028	0.011	-10000	0	-10000	0	0
NFKB1	0.038	0.064	0.19	49	-10000	0	49
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.031	0.16	1	-0.26	3	4
PTPN6	0.02	0.049	-10000	0	-0.3	2	2
TEC/VAV2/GRB2	0.043	0.058	0.28	1	-10000	0	1
EPOR	0.027	0.024	-10000	0	-0.39	1	1
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
mol:GDP	0.05	0.051	0.27	1	-0.31	1	2
SOS1	0.027	0.002	-10000	0	-10000	0	0
PLCG2	-0.015	0.13	-10000	0	-0.4	45	45
CRKL/CBL/C3G	0.047	0.05	0.28	1	-10000	0	1
VAV2	0.017	0.053	0.3	1	-0.26	1	2
CBL	0.02	0.05	0.3	1	-0.29	2	3
SHC/Grb2/SOS1	0.038	0.043	-10000	0	-0.31	1	1
STAT5A	0.027	0.045	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
STAT5 (dimer)	0.04	0.069	-10000	0	-10000	0	0
LYN/PLCgamma2	0.008	0.088	-10000	0	-0.28	38	38
PTPN11	0.027	0.003	-10000	0	-10000	0	0
BTK	-0.005	0.086	0.3	1	-0.3	9	10
BCL2	0.01	0.17	-10000	0	-0.72	22	22

×

PDGFR-alpha 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
PDGFRA	0.021	0.069	-10000	0	-0.39	12	12
PDGF/PDGFRA/CRKL	0.034	0.05	-10000	0	-0.26	12	12
positive regulation of JUN kinase activity	0.06	0.045	-10000	0	-10000	0	0
CRKL	0.026	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.027	0.055	-10000	0	-0.27	14	14
AP1	0.022	0.087	-10000	0	-0.52	3	3
mol:IP3	0.003	0.042	-10000	0	-0.28	9	9
PLCG1	0.003	0.042	-10000	0	-0.28	9	9
PDGF/PDGFRA/alphaV Integrin	0.035	0.051	-10000	0	-0.26	12	12
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1
CRK	0.023	0.01	-10000	0	-10000	0	0
mol:Ca2+	0.003	0.042	-10000	0	-0.28	9	9
CAV3	-0.013	0.032	-10000	0	-0.43	2	2
CAV1	0.023	0.04	-10000	0	-0.4	4	4
SHC/Grb2/SOS1	0.062	0.046	-10000	0	-10000	0	0
PDGF/PDGFRA/Shf	0.022	0.078	-10000	0	-0.29	26	26
FOS	-0.004	0.071	0.31	9	-0.52	3	12
JUN	-0.007	0.019	-10000	0	-10000	0	0
oligodendrocyte development	0.035	0.051	-10000	0	-0.26	12	12
GRB2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:DAG	0.003	0.042	-10000	0	-0.28	9	9
PDGF/PDGFRA	0.021	0.069	-10000	0	-0.39	12	12
actin cytoskeleton reorganization	0.034	0.051	-10000	0	-0.26	12	12
SRF	0.005	0.012	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.049	0.045	-10000	0	-0.22	10	10
PDGF/PDGFRA/Crk/C3G	0.04	0.05	-10000	0	-0.22	11	11
JAK1	0.01	0.045	-10000	0	-0.27	11	11
ELK1/SRF	0.022	0.075	0.23	2	-10000	0	2
SHB	0.027	0.004	-10000	0	-10000	0	0
SHF	0.012	0.078	-10000	0	-0.42	14	14
CSNK2A1	0.013	0.02	-10000	0	-10000	0	0
GO:0007205	-0.002	0.044	-10000	0	-0.31	9	9
SOS1	0.027	0.002	-10000	0	-10000	0	0
Ras protein signal transduction	0.06	0.045	-10000	0	-10000	0	0
PDGF/PDGFRA/SHB	0.034	0.051	-10000	0	-0.26	12	12
PDGF/PDGFRA/Caveolin-1	0.033	0.057	-10000	0	-0.28	13	13
ITGAV	0.027	0.002	-10000	0	-10000	0	0
ELK1	-0.007	0.039	0.25	1	-0.26	9	10
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.029	0.051	-10000	0	-0.26	12	12
JAK-STAT cascade	0.01	0.045	-10000	0	-0.27	11	11
cell proliferation	0.022	0.078	-10000	0	-0.28	26	26

×

ceramide signaling pathway

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
MAP4K4	0.023	0.053	-10000	0	-0.3	2	2
BAG4	0.023	0.01	-10000	0	-10000	0	0
BAD	0.013	0.03	-10000	0	-0.36	1	1
NFKBIA	0.025	0.007	-10000	0	-10000	0	0
BIRC3	0.019	0.057	-10000	0	-0.4	8	8
BAX	0.015	0.032	0.16	7	-0.19	1	8
EnzymeConsortium:3.1.4.12	0.009	0.015	0.06	4	-0.07	1	5
IKBKB	0.037	0.07	0.21	27	-0.31	1	28
MAP2K2	0.014	0.043	0.19	13	-0.31	1	14
MAP2K1	0.014	0.04	0.19	13	-10000	0	13
SMPD1	0.009	0.029	0.12	3	-0.17	7	10
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.029	0.056	0.22	1	-0.36	1	2
MAP2K4	0.009	0.026	0.14	1	-0.23	1	2
protein ubiquitination	0.028	0.058	-10000	0	-0.31	2	2
EnzymeConsortium:2.7.1.37	0.016	0.043	0.19	14	-0.23	1	15
response to UV	0	0	0.002	15	-10000	0	15
RAF1	0.016	0.041	0.19	13	-0.18	1	14
CRADD	0.027	0.003	-10000	0	-10000	0	0
mol:ceramide	0.016	0.029	0.1	7	-0.2	1	8
I-kappa-B-alpha/RELA/p50/ubiquitin	0.034	0.011	-10000	0	-10000	0	0
MADD	0.027	0.003	-10000	0	-10000	0	0
MAP3K1	0.014	0.029	0.12	1	-0.22	2	3
TRADD	0.027	0.002	-10000	0	-10000	0	0
RELA/p50	0.027	0.004	-10000	0	-10000	0	0
MAPK3	0.018	0.042	0.19	14	-0.24	1	15
MAPK1	0.014	0.045	0.19	12	-0.24	1	13
p50/RELA/I-kappa-B-alpha	0.037	0.012	-10000	0	-10000	0	0
FADD	0.025	0.052	0.22	1	-0.29	2	3
KSR1	0.017	0.04	0.19	13	-0.19	1	14
MAPK8	0.009	0.028	-10000	0	-0.22	1	1
TRAF2	0.026	0.02	-10000	0	-0.4	1	1
response to radiation	0	0	0.002	5	-10000	0	5
CHUK	0.022	0.05	0.21	1	-0.29	1	2
TNF R/SODD	0.034	0.015	-10000	0	-10000	0	0
TNF	0.025	0.029	-10000	0	-0.4	2	2
CYCS	0.036	0.048	0.13	36	-0.28	1	37
IKBKG	0.022	0.056	-10000	0	-0.36	2	2
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.027	0.055	-10000	0	-0.3	3	3
RELA	0.027	0.004	-10000	0	-10000	0	0
RIPK1	0.027	0.003	-10000	0	-10000	0	0
AIFM1	0.031	0.045	0.13	25	-0.28	1	26
TNF/TNF R/SODD	0.044	0.028	-10000	0	-0.24	2	2
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
response to heat	0	0	0.002	5	-10000	0	5
CASP8	0.026	0.09	-10000	0	-0.55	10	10
NSMAF	0.043	0.077	0.21	51	-0.32	1	52
response to hydrogen peroxide	0	0	0.002	15	-10000	0	15
BCL2	0.012	0.059	-10000	0	-0.4	9	9

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.002	0.064	-10000	0	-0.43	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.007	0.093	0.44	3	-10000	0	3
IL27/IL27R/JAK1	0.03	0.11	-10000	0	-0.56	1	1
TBX21	-0.026	0.13	-10000	0	-0.51	17	17
IL12B	0.014	0.045	-10000	0	-0.43	4	4
IL12A	0.001	0.033	-10000	0	-0.28	6	6
IL6ST	0.018	0.058	-10000	0	-0.41	8	8
IL27RA/JAK1	0.022	0.027	-10000	0	-10000	0	0
IL27	0.007	0.079	-10000	0	-0.43	14	14
TYK2	0.023	0.015	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.041	0.14	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.007	0.093	0.44	3	-10000	0	3
T cell proliferation during immune response	0.007	0.093	0.44	3	-10000	0	3
MAPKKK cascade	-0.007	0.093	-10000	0	-0.44	3	3
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT2	0.027	0.002	-10000	0	-10000	0	0
STAT1	0.027	0.022	-10000	0	-0.43	1	1
IL12RB1	0.011	0.081	-10000	0	-0.4	17	17
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.019	0.12	-10000	0	-0.55	8	8
IL27/IL27R/JAK2/TYK2	-0.007	0.094	-10000	0	-0.44	3	3
positive regulation of T cell mediated cytotoxicity	-0.007	0.093	-10000	0	-0.44	3	3
STAT1 (dimer)	0.03	0.16	-10000	0	-0.6	5	5
JAK2	0.022	0.038	-10000	0	-0.4	3	3
JAK1	0.027	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	0.004	0.098	-10000	0	-0.42	3	3
T cell proliferation	-0.05	0.12	-10000	0	-0.42	12	12
IL12/IL12R/TYK2/JAK2	0.005	0.14	-10000	0	-0.76	12	12
IL17A	-0.042	0.14	-10000	0	-10000	0	0
mast cell activation	0.007	0.093	0.44	3	-10000	0	3
IFNG	0.001	0.026	-10000	0	-0.12	1	1
T cell differentiation	-0.001	0.004	-10000	0	-0.018	3	3
STAT3 (dimer)	0.004	0.097	-10000	0	-0.45	2	2
STAT5A (dimer)	0.004	0.097	-10000	0	-0.45	2	2
STAT4 (dimer)	-0.005	0.12	-10000	0	-0.4	16	16
STAT4	0.006	0.093	-10000	0	-0.4	23	23
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	-0.015	0.12	-10000	0	-1.2	4	4
IL18	0.005	0.019	-10000	0	-0.28	2	2
positive regulation of mast cell cytokine production	0.004	0.096	-10000	0	-0.44	2	2
IL27/EBI3	-0.001	0.11	-10000	0	-0.3	50	50
IL27RA	0.008	0.025	-10000	0	-10000	0	0
IL6	-0.067	0.18	0.33	5	-0.45	70	75
STAT5A	0.027	0.004	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.015	0.014	-10000	0	-10000	0	0
IL1B	-0.028	0.096	-10000	0	-0.3	50	50
EBI3	-0.008	0.12	-10000	0	-0.4	37	37
TNF	0.005	0.019	-10000	0	-0.28	2	2

×

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	0.026	0.006	-10000	0	-10000	0	0
HDAC2	0.027	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.038	0.056	-10000	0	-0.23	16	16
forebrain development	0.005	0.091	-10000	0	-0.54	5	5
GNAO1	-0.087	0.19	-10000	0	-0.4	122	122
SMO/beta Arrestin2	0.034	0.018	-10000	0	-10000	0	0
SMO	0.027	0.007	-10000	0	-10000	0	0
ARRB2	0.023	0.011	-10000	0	-10000	0	0
GLI3/SPOP	0.044	0.084	0.24	2	-0.31	3	5
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.027	0.002	-10000	0	-10000	0	0
GNAI2	0.027	0.005	-10000	0	-10000	0	0
SIN3/HDAC complex	0.05	0.032	-10000	0	-10000	0	0
GNAI1	0.014	0.071	-10000	0	-0.4	13	13
XPO1	0.028	0.008	-10000	0	-10000	0	0
GLI1/Su(fu)	0.002	0.095	-10000	0	-0.58	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	0.021	0.047	-10000	0	-0.39	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	0.059	0.18	1	-0.28	11	12
GLI3	0.032	0.086	0.24	3	-0.33	5	8
CSNK1D	0.027	0.004	-10000	0	-10000	0	0
CSNK1E	0.026	0.006	-10000	0	-10000	0	0
SAP18	0.021	0.011	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.021	0.012	-10000	0	-10000	0	0
GNG2	0.009	0.081	-10000	0	-0.4	17	17
Gi family/GTP	-0.045	0.12	-10000	0	-0.33	34	34
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.026	0.006	-10000	0	-10000	0	0
GLI3/Su(fu)	0.038	0.076	0.24	3	-0.32	3	6
GLI2/Su(fu)	0.021	0.062	-10000	0	-0.34	6	6
FOXA2	-0.004	0.16	-10000	0	-0.69	16	16
neural tube patterning	0.005	0.091	-10000	0	-0.54	5	5
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	0.007	-10000	0	-10000	0	0
CSNK1G2	0.026	0.02	-10000	0	-0.4	1	1
CSNK1G3	0.027	0.005	-10000	0	-10000	0	0
MTSS1	0.021	0.047	-10000	0	-0.39	5	5
embryonic limb morphogenesis	0.005	0.091	-10000	0	-0.54	5	5
SUFU	0.021	0.011	-10000	0	-10000	0	0
LGALS3	0.025	0.021	-10000	0	-0.4	1	1
catabolic process	0.048	0.098	0.25	1	-0.35	7	8
GLI3A/CBP	0.031	0.029	-10000	0	-0.32	3	3
KIF3A	0.027	0.005	-10000	0	-10000	0	0
GLI1	0.004	0.093	-10000	0	-0.56	5	5
RAB23	0.027	0.003	-10000	0	-10000	0	0
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
IFT172	0.027	0.001	-10000	0	-10000	0	0
RBBP7	0.027	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.027	0.04	-10000	0	-10000	0	0
GNAZ	0.022	0.045	-10000	0	-0.4	5	5
RBBP4	0.026	0.006	-10000	0	-10000	0	0
CSNK1G1	0.025	0.021	-10000	0	-0.4	1	1
PIAS1	0.026	0.006	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.027	0.06	-10000	0	-0.32	4	4
STK36	0.028	0.008	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.046	0.14	-10000	0	-0.37	46	46
PTCH1	0.003	0.11	-10000	0	-1	3	3
MIM/GLI1	0.012	0.11	-10000	0	-0.53	7	7
CREBBP	0.031	0.029	-10000	0	-0.32	3	3
Su(fu)/SIN3/HDAC complex	0.024	0.088	0.24	1	-0.33	19	20

×

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

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
BAG4	0.023	0.01	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.028	0.072	-10000	0	-0.36	4	4
NEF	-0.006	0.038	-10000	0	-0.26	2	2
NFKBIA	0.025	0.018	-10000	0	-10000	0	0
BIRC3	0.013	0.062	-10000	0	-0.44	8	8
CYCS	0.01	0.085	0.18	39	-0.36	5	44
RIPK1	0.027	0.003	-10000	0	-10000	0	0
CD247	0.007	0.092	-10000	0	-0.47	13	13
MAP2K7	0.018	0.11	-10000	0	-0.58	9	9
protein ubiquitination	0.027	0.045	0.2	7	-0.29	1	8
CRADD	0.027	0.003	-10000	0	-10000	0	0
DAXX	0.027	0.003	-10000	0	-10000	0	0
FAS	0.022	0.045	-10000	0	-0.4	5	5
BID	0.001	0.074	0.19	7	-0.26	22	29
NF-kappa-B/RelA/I kappa B alpha	0.051	0.044	-10000	0	-0.24	7	7
TRADD	0.027	0.002	-10000	0	-10000	0	0
MAP3K5	0.027	0.004	-10000	0	-10000	0	0
CFLAR	0.027	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	0.051	0.044	-10000	0	-0.24	8	8
MAPK8	0.016	0.099	-10000	0	-0.56	8	8
APAF1	0.027	0.003	-10000	0	-10000	0	0
TRAF1	0.027	0.003	-10000	0	-10000	0	0
TRAF2	0.026	0.02	-10000	0	-0.4	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.008	0.079	0.2	8	-0.26	27	35
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.033	0.045	-10000	0	-0.32	2	2
CHUK	0.028	0.047	0.23	2	-0.31	1	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.073	0.036	-10000	0	-10000	0	0
TCRz/NEF	0.001	0.093	-10000	0	-0.32	33	33
TNF	0.025	0.029	-10000	0	-0.4	2	2
FASLG	-0.017	0.14	-10000	0	-0.48	33	33
NFKB1	0.026	0.017	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.045	0.029	-10000	0	-0.24	2	2
CASP6	0.031	0.1	-10000	0	-0.45	11	11
CASP7	0.013	0.095	-10000	0	-0.44	10	10
RELA	0.027	0.017	-10000	0	-10000	0	0
CASP2	0.027	0.005	-10000	0	-10000	0	0
CASP3	0.01	0.094	-10000	0	-0.44	10	10
TNFRSF1A	0.027	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.034	0.015	-10000	0	-10000	0	0
CASP8	0.027	0.001	-10000	0	-10000	0	0
CASP9	0.026	0.007	-10000	0	-10000	0	0
MAP3K14	0.031	0.049	0.2	5	-0.36	1	6
APAF-1/Caspase 9	0.022	0.08	-10000	0	-0.34	3	3
BCL2	0.008	0.091	-10000	0	-0.5	8	8

×

TCGA08_rtk_signaling

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
PDGFRA	0.015	0.068	-10000	0	-0.4	12	12
HRAS	0.026	0.02	-10000	0	-0.4	1	1
EGFR	0.024	0.021	-10000	0	-0.4	1	1
AKT	0.036	0.073	0.26	8	-0.3	5	13
FOXO3	0.027	0.004	-10000	0	-10000	0	0
AKT1	0.025	0.007	-10000	0	-10000	0	0
FOXO1	0.02	0.023	-10000	0	-0.4	1	1
AKT3	0.02	0.053	-10000	0	-0.4	7	7
FOXO4	0.027	0.002	-10000	0	-10000	0	0
MET	0.023	0.046	0.36	1	-0.43	4	5
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
PIK3CB	0.027	0.003	-10000	0	-10000	0	0
NRAS	0.025	0.029	-10000	0	-0.4	2	2
PIK3CG	-0.035	0.15	-10000	0	-0.4	65	65
PIK3R3	0.027	0.004	-10000	0	-10000	0	0
PIK3R2	0.027	0.003	-10000	0	-10000	0	0
NF1	0.026	0.005	-10000	0	-10000	0	0
RAS	0.023	0.04	0.17	5	-0.28	1	6
ERBB2	0.029	0.032	0.36	4	-10000	0	4
proliferation/survival/translation	-0.025	0.066	0.22	17	-0.23	1	18
PI3K	0.023	0.062	0.24	12	-0.22	6	18
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
KRAS	0.027	0.003	-10000	0	-10000	0	0
FOXO	0.061	0.051	0.22	13	-10000	0	13
AKT2	0.027	0.004	-10000	0	-10000	0	0
PTEN	0.026	0.006	-10000	0	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.001	0.13	-10000	0	-0.78	4	4
RAD9A	0.027	0.004	-10000	0	-10000	0	0
AP1	0.035	0.028	-10000	0	-0.27	3	3
IFNAR2	0.025	0.012	-10000	0	-10000	0	0
AKT1	-0.003	0.067	-10000	0	-0.31	12	12
ER alpha/Oestrogen	-0.006	0.083	-10000	0	-0.28	39	39
NFX1/SIN3/HDAC complex	0.037	0.047	-10000	0	-0.29	2	2
EGF	-0.06	0.17	-10000	0	-0.4	89	89
SMG5	0.027	0.004	-10000	0	-10000	0	0
SMG6	0.023	0.01	-10000	0	-10000	0	0
SP3/HDAC2	0.037	0.018	-10000	0	-10000	0	0
TERT/c-Abl	0.011	0.13	-10000	0	-0.73	4	4
SAP18	0.022	0.011	-10000	0	-10000	0	0
MRN complex	0.045	0.026	-10000	0	-0.24	1	1
WT1	-0.19	0.23	0.36	4	-0.43	218	222
WRN	0.021	0.023	-10000	0	-0.4	1	1
SP1	0.024	0.016	-10000	0	-10000	0	0
SP3	0.027	0.004	-10000	0	-10000	0	0
TERF2IP	0.027	0.002	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.029	0.13	-10000	0	-0.74	3	3
Mad/Max	0.036	0.025	-10000	0	-0.28	2	2
TERT	0.001	0.14	-10000	0	-0.82	4	4
CCND1	0.001	0.12	-10000	0	-0.78	3	3
MAX	0.025	0.008	-10000	0	-10000	0	0
RBBP7	0.027	0.003	-10000	0	-10000	0	0
RBBP4	0.026	0.006	-10000	0	-10000	0	0
TERF2	0.024	0.007	-10000	0	-10000	0	0
PTGES3	0.027	0.002	-10000	0	-10000	0	0
SIN3A	0.026	0.006	-10000	0	-10000	0	0
Telomerase/911	0.041	0.048	-10000	0	-0.32	2	2
CDKN1B	-0.005	0.081	-10000	0	-0.27	1	1
RAD1	0.028	0.016	0.36	1	-10000	0	1
XRCC5	0.027	0.001	-10000	0	-10000	0	0
XRCC6	0.026	0.006	-10000	0	-10000	0	0
SAP30	0.026	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.037	0.011	-10000	0	-10000	0	0
UBE3A	0.025	0.021	-10000	0	-0.4	1	1
JUN	0.027	0.006	-10000	0	-10000	0	0
E6	0	0.002	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.017	0.018	-10000	0	-0.28	1	1
FOS	0.023	0.035	-10000	0	-0.4	3	3
IFN-gamma/IRF1	0.011	0.1	-10000	0	-0.3	44	44
PARP2	0.026	0.007	-10000	0	-10000	0	0
BLM	0.026	0.006	-10000	0	-10000	0	0
Telomerase	-0.003	0.12	-10000	0	-0.68	9	9
IRF1	0.03	0.006	-10000	0	-10000	0	0
ESR1	-0.01	0.12	-10000	0	-0.4	39	39
KU/TER	0.039	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.04	0.006	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.032	0.06	-10000	0	-0.3	5	5
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.032	0.06	-10000	0	-0.31	5	5
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC2	0.024	0.016	-10000	0	-10000	0	0
ATM	0.01	0.002	-10000	0	-10000	0	0
SMAD3	0.012	0.016	-10000	0	-0.3	1	1
ABL1	0.027	0.004	-10000	0	-10000	0	0
MXD1	0.025	0.028	-10000	0	-0.4	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	0.021	-10000	0	-0.4	1	1
TERT/NF kappa B1/14-3-3	0.012	0.14	-10000	0	-0.71	5	5
NR2F2	0.026	0.007	-10000	0	-10000	0	0
MAPK3	-0.008	0.018	-10000	0	-0.29	1	1
MAPK1	-0.007	0.013	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.026	0.022	-10000	0	-0.43	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	0.01	0.002	-10000	0	-10000	0	0
NBN	0.022	0.022	-10000	0	-0.4	1	1
EGFR	0.024	0.021	-10000	0	-0.39	1	1
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	-0.024	0.12	-10000	0	-0.28	81	81
MYC	0.025	0.048	0.36	5	-0.42	2	7
IL2	0.017	0.017	-10000	0	-10000	0	0
KU	0.039	0.009	-10000	0	-10000	0	0
RAD50	0.027	0.004	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
TGFB1	0.026	0.022	-10000	0	-0.43	1	1
TRF2/BLM	0.038	0.01	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.023	0.13	-10000	0	-0.73	4	4
SP1/HDAC2	0.037	0.023	-10000	0	-10000	0	0
PINX1	0.021	0.012	-10000	0	-10000	0	0
Telomerase/EST1A	0.024	0.12	-10000	0	-0.89	2	2
Smad3/Myc	0.024	0.035	0.25	5	-0.26	3	8
911 complex	0.049	0.021	0.25	1	-10000	0	1
IFNG	-0.016	0.13	-10000	0	-0.42	44	44
Telomerase/PinX1	0.017	0.12	-10000	0	-0.89	2	2
Telomerase/AKT1/mTOR/p70S6K	0	0.1	-10000	0	-0.46	10	10
SIN3B	0.027	0.003	-10000	0	-10000	0	0
YWHAE	0.023	0.01	-10000	0	-10000	0	0
Telomerase/EST1B	0.027	0.12	-10000	0	-0.74	3	3
response to DNA damage stimulus	0.003	0.014	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.063	0.033	-10000	0	-10000	0	0
TRF2/WRN	0.03	0.022	-10000	0	-0.26	1	1
Telomerase/hnRNP C1/C2	0.029	0.12	-10000	0	-0.74	3	3
E2F1	0.02	0.057	0.36	8	-0.43	2	10
ZNFX1	0.016	0.014	-10000	0	-10000	0	0
PIF1	0.016	0.067	-10000	0	-0.43	10	10
NCL	0.027	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

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.02	0.067	-10000	0	-0.21	31	31
MAPK9	0.007	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.01	0.02	-10000	0	-0.3	2	2
GNB1/GNG2	0.023	0.052	-10000	0	-0.23	17	17
GNB1	0.026	0.007	-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	0.005	0.043	-10000	0	-0.21	17	17
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	0.011	0.058	17	-10000	0	17
GNAL	0.006	0.08	-10000	0	-0.4	17	17
GNG2	0.009	0.081	-10000	0	-0.4	17	17
CRH	-0.017	0.029	-10000	0	-0.43	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.001	-10000	0	-10000	0	0
MAPK11	0.006	0.011	-10000	0	-0.15	2	2

×

FOXM1 transcription factor network

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
NFATC3	0.068	0.23	-10000	0	-1	1	1
PLK1	0.041	0.089	-10000	0	-0.83	4	4
BIRC5	0.039	0.098	-10000	0	-0.8	5	5
HSPA1B	0.061	0.24	-10000	0	-0.91	2	2
MAP2K1	0.035	0.036	-10000	0	-10000	0	0
BRCA2	0.11	0.24	-10000	0	-1	1	1
FOXM1	0.069	0.26	-10000	0	-1	3	3
XRCC1	0.07	0.23	-10000	0	-1	1	1
FOXM1B/p19	0.033	0.26	-10000	0	-0.91	4	4
Cyclin D1/CDK4	0.077	0.22	-10000	0	-0.93	1	1
CDC2	0.069	0.24	-10000	0	-0.89	3	3
TGFA	0.068	0.22	-10000	0	-0.89	1	1
SKP2	0.071	0.23	-10000	0	-1	1	1
CCNE1	0.029	0.032	0.36	2	-0.42	1	3
CKS1B	0.069	0.23	-10000	0	-0.85	3	3
RB1	0.056	0.13	-10000	0	-0.7	2	2
FOXM1C/SP1	0.074	0.25	-10000	0	-0.93	3	3
AURKB	-0.097	0.33	-10000	0	-0.8	78	78
CENPF	0.072	0.23	-10000	0	-1	1	1
CDK4	0.029	0.027	-10000	0	-0.41	1	1
MYC	0.053	0.21	-10000	0	-0.79	2	2
CHEK2	0.035	0.036	-10000	0	-10000	0	0
ONECUT1	0.069	0.23	-10000	0	-0.87	2	2
CDKN2A	-0.074	0.19	0.36	2	-0.44	97	99
LAMA4	0.068	0.23	-10000	0	-1	1	1
FOXM1B/HNF6	0.068	0.24	-10000	0	-0.99	2	2
FOS	0.059	0.27	-10000	0	-1.1	8	8
SP1	0.027	0.007	-10000	0	-10000	0	0
CDC25B	0.088	0.24	-10000	0	-1.1	1	1
response to radiation	0.012	0.02	-10000	0	-10000	0	0
CENPB	0.092	0.24	-10000	0	-1	1	1
CENPA	0.068	0.23	-10000	0	-1	1	1
NEK2	0.072	0.23	-10000	0	-0.89	2	2
HIST1H2BA	0.064	0.23	-10000	0	-1	1	1
CCNA2	0.028	0.012	-10000	0	-10000	0	0
EP300	0.026	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.065	0.25	-10000	0	-1	2	2
CCNB2	0.068	0.23	-10000	0	-1	1	1
CCNB1	0.069	0.24	-10000	0	-0.94	2	2
ETV5	0.066	0.23	-10000	0	-1	1	1
ESR1	0.006	0.39	-10000	0	-1.1	41	41
CCND1	0.068	0.22	-10000	0	-0.95	1	1
GSK3A	0.033	0.033	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.063	0.041	0.23	2	-0.23	1	3
CDK2	0.029	0.011	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.024	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.078	0.24	-10000	0	-0.9	3	3
GAS1	-0.026	0.44	-10000	0	-1.1	59	59
MMP2	0.064	0.25	-10000	0	-1.2	3	3
RB1/FOXM1C	0.054	0.21	-10000	0	-0.99	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.05	0.058	-10000	0	-0.21	14	14
HDAC3	0.027	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.008	0.001	-10000	0	-10000	0	0
GATA1/HDAC4	0.038	0.006	-10000	0	-10000	0	0
GATA1/HDAC5	0.036	0.017	-10000	0	-0.28	1	1
GATA2/HDAC5	0.031	0.052	-10000	0	-0.28	12	12
HDAC5/BCL6/BCoR	0.053	0.018	-10000	0	-0.24	1	1
HDAC9	-0.031	0.14	-10000	0	-0.4	59	59
Glucocorticoid receptor/Hsp90/HDAC6	0.032	0.072	-10000	0	-0.23	30	30
HDAC4/ANKRA2	0.04	0.007	-10000	0	-10000	0	0
HDAC5/YWHAB	0.022	0.025	-10000	0	-0.28	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.013	-10000	0	-0.18	2	2
GATA2	0.017	0.065	-10000	0	-0.4	11	11
HDAC4/RFXANK	0.04	0.005	-10000	0	-10000	0	0
BCOR	0.027	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.025	0.021	-10000	0	-0.4	1	1
HDAC5	0.026	0.02	-10000	0	-0.4	1	1
GNB1/GNG2	0.024	0.061	-10000	0	-0.28	17	17
Histones	0.003	0.082	-10000	0	-0.31	7	7
ADRBK1	0.027	0.004	-10000	0	-10000	0	0
HDAC4	0.027	0.002	-10000	0	-10000	0	0
XPO1	0.027	0.001	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.038	0.017	-10000	0	-0.28	1	1
HDAC4/Ubc9	0.04	0.006	-10000	0	-10000	0	0
HDAC7	0.027	0.002	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.033	0.021	-10000	0	-0.28	1	1
TUBA1B	0.027	0.002	-10000	0	-10000	0	0
HDAC6	0.027	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.039	0.017	-10000	0	-0.28	1	1
CAMK4	0.002	0.097	-10000	0	-0.4	25	25
Tubulin/HDAC6	0.049	0.042	-10000	0	-0.26	8	8
SUMO1	0.026	0.028	-10000	0	-0.4	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	0.11	-10000	0	-0.4	30	30
SUMO1/HDAC4	0.037	0.036	-10000	0	-0.27	2	2
SRF	0.027	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.024	0.02	-10000	0	-10000	0	0
Tubulin	0.034	0.046	-10000	0	-0.3	8	8
HDAC4/14-3-3 E	0.034	0.016	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
RANGAP1	0.026	0.006	-10000	0	-10000	0	0
BCL6/BCoR	0.04	0.006	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.054	0.017	-10000	0	-0.24	1	1
HDAC4/SRF	0.035	0.067	-10000	0	-0.24	25	25
HDAC4/ER alpha	0.012	0.09	-10000	0	-0.28	39	39
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.003	0.081	-10000	0	-0.31	7	7
cell motility	0.048	0.042	-10000	0	-0.26	8	8
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
HDAC7/HDAC3	0.04	0.006	-10000	0	-10000	0	0
BCL6	0.027	0.002	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.027	0.002	-10000	0	-10000	0	0
Hsp90/HDAC6	0.037	0.011	-10000	0	-10000	0	0
ESR1	-0.012	0.12	-10000	0	-0.4	39	39
HDAC6/HDAC11	0.04	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.038	0.032	-10000	0	-10000	0	0
NPC	0.016	0	-10000	0	-10000	0	0
MEF2C	0.017	0.062	-10000	0	-0.4	10	10
RAN	0.027	0.002	-10000	0	-10000	0	0
HDAC4/MEF2C	0.069	0.048	-10000	0	-10000	0	0
GNG2	0.009	0.081	-10000	0	-0.4	17	17
NCOR2	0.026	0.02	-10000	0	-0.4	1	1
TUBB2A	0.019	0.06	-10000	0	-0.43	8	8
HDAC11	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
RANBP2	0.027	0	-10000	0	-10000	0	0
ANKRA2	0.027	0.004	-10000	0	-10000	0	0
RFXANK	0.027	0.003	-10000	0	-10000	0	0
nuclear import	-0.019	0.022	0.24	1	-10000	0	1

×

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

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
MET/RANBP9	0.036	0.038	0.26	1	-0.3	5	6
CRKL	0.026	0.094	0.29	3	-0.44	11	14
mol:PIP3	-0.004	0.04	-10000	0	-0.82	1	1
AKT1	-0.009	0.038	-10000	0	-0.72	1	1
PTK2B	0.02	0.023	-10000	0	-0.4	1	1
RAPGEF1	0.028	0.093	0.27	5	-0.42	11	16
RANBP10	0.027	0.001	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.044	0.051	-10000	0	-0.24	13	13
MAP3K5	0.012	0.12	0.24	1	-0.44	15	16
HGF/MET/CIN85/CBL/ENDOPHILINS	0.058	0.051	-10000	0	-0.23	4	4
AP1	0.028	0.033	-10000	0	-0.25	2	2
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
apoptosis	-0.039	0.24	-10000	0	-0.75	43	43
STAT3 (dimer)	0.007	0.048	-10000	0	-0.3	3	3
GAB1/CRKL/SHP2/PI3K	0.065	0.093	0.35	1	-0.43	8	9
INPP5D	0.026	0.02	-10000	0	-0.4	1	1
CBL/CRK	0.047	0.092	0.28	4	-0.42	10	14
PTPN11	0.027	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0.013	-10000	0	-10000	0	0
PTEN	0.026	0.006	-10000	0	-10000	0	0
ELK1	0.003	0.087	0.32	22	-10000	0	22
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.008	0.041	-10000	0	-0.23	4	4
PAK1	-0.009	0.038	-10000	0	-0.69	1	1
HGF/MET/RANBP10	0.045	0.051	-10000	0	-0.24	13	13
HRAS	0.021	0.059	0.33	1	-0.42	2	3
DOCK1	0.028	0.089	0.28	3	-0.42	11	14
GAB1	0.018	0.089	-10000	0	-0.48	10	10
CRK	0.024	0.088	0.32	2	-0.46	9	11
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.076	-10000	0	-0.43	10	10
JUN	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.011	0.038	-10000	0	-0.18	10	10
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
cell morphogenesis	0.047	0.096	0.3	9	-0.4	2	11
GRB2/SHC	0.01	0.053	-10000	0	-0.2	3	3
FOS	0.023	0.035	-10000	0	-0.4	3	3
GLMN	0.002	0.01	-10000	0	-0.22	1	1
cell motility	0.003	0.086	0.32	22	-10000	0	22
HGF/MET/MUC20	0.027	0.047	-10000	0	-0.24	13	13
cell migration	0.01	0.053	-10000	0	-0.2	3	3
GRB2	0.027	0.004	-10000	0	-10000	0	0
CBL	0.027	0.004	-10000	0	-10000	0	0
MET/RANBP10	0.037	0.035	0.26	1	-0.3	4	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.015	0.045	-10000	0	-0.28	6	6
MET/MUC20	0.017	0.032	0.24	1	-0.3	4	5
RAP1B	0.026	0.089	0.28	3	-0.41	10	13
RAP1A	0.026	0.088	0.26	5	-0.4	10	15
HGF/MET/RANBP9	0.043	0.053	-10000	0	-0.24	14	14
RAF1	0.024	0.062	0.31	1	-0.4	2	3
STAT3	0.007	0.048	-10000	0	-0.31	3	3
cell proliferation	0.026	0.064	0.26	1	-0.37	3	4
RPS6KB1	0.004	0.034	-10000	0	-0.26	5	5
MAPK3	-0.014	0.076	0.54	4	-10000	0	4
MAPK1	0.017	0.16	0.67	23	-10000	0	23
RANBP9	0.026	0.02	-10000	0	-0.4	1	1
MAPK8	0.024	0.11	-10000	0	-0.47	6	6
SRC	0.006	0.034	-10000	0	-0.26	4	4
PI3K	0.011	0.053	-10000	0	-0.2	2	2
MET/Glomulin	-0.014	0.054	0.2	1	-0.19	15	16
SOS1	0.027	0.002	-10000	0	-10000	0	0
MAP2K1	0.021	0.059	0.3	1	-0.41	1	2
MET	0.023	0.046	0.36	1	-0.43	4	5
MAP4K1	0.013	0.13	0.25	2	-0.46	16	18
PTK2	0.023	0.01	-10000	0	-10000	0	0
MAP2K2	0.021	0.061	0.3	1	-0.37	3	4
BAD	-0.01	0.037	-10000	0	-0.69	1	1
MAP2K4	0.007	0.1	0.24	2	-0.41	12	14
SHP2/GRB2/SOS1/GAB1	0.048	0.083	0.26	1	-0.42	7	8
INPPL1	0.027	0.004	-10000	0	-10000	0	0
PXN	0.027	0.002	-10000	0	-10000	0	0
SH3KBP1	0.027	0.003	-10000	0	-10000	0	0
HGS	-0.013	0.034	-10000	0	-0.21	3	3
PLCgamma1/PKC	0.012	0.01	-10000	0	-10000	0	0
HGF	0.017	0.06	-10000	0	-0.4	9	9
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.002	-10000	0	-10000	0	0
PTPRJ	0.027	0.003	-10000	0	-10000	0	0
NCK/PLCgamma1	0.026	0.033	-10000	0	-10000	0	0
PDPK1	-0.008	0.041	-10000	0	-0.76	1	1
HGF/MET/SHIP	0.044	0.053	-10000	0	-0.24	14	14

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.004	-10000	0	-10000	0	0
mol:PIP3	0.007	0.012	-10000	0	-10000	0	0
FRAP1	-0.009	0.11	-10000	0	-0.43	25	25
AKT1	0.002	0.026	0.16	4	-10000	0	4
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	-10000	0	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.006	0.039	-10000	0	-0.22	5	5
TSC2	0.027	0.003	-10000	0	-10000	0	0
RHEB/GDP	0.02	0.029	-10000	0	-10000	0	0
TSC1	0.027	0.003	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.024	0.017	-10000	0	-0.18	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.017	0.048	-10000	0	-0.25	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	0.008	0.071	0.21	1	-0.3	13	14
MAP3K5	0.005	0.026	0.2	2	-0.17	7	9
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
apoptosis	0.006	0.026	0.2	2	-0.17	7	9
mol:LY294002	0	0	-10000	0	-0.001	2	2
EIF4B	0.007	0.065	0.19	2	-0.32	6	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.028	0.066	0.2	1	-0.3	6	7
eIF4E/eIF4G1/eIF4A1	0.004	0.064	-10000	0	-0.26	23	23
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.038	0.022	-10000	0	-0.2	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.03	0.18	4	-10000	0	4
FKBP1A	0.022	0.011	-10000	0	-10000	0	0
RHEB/GTP	0.034	0.038	0.2	1	-10000	0	1
mol:Amino Acids	0	0	-10000	0	-0.001	2	2
FKBP12/Rapamycin	0.016	0.008	-10000	0	-10000	0	0
PDPK1	-0.005	0.016	0.16	2	-10000	0	2
EIF4E	0.025	0.028	-10000	0	-0.4	2	2
ASK1/PP5C	0.01	0.12	-10000	0	-0.43	28	28
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.008	0.051	-10000	0	-0.26	9	9
TSC1/TSC2	0.034	0.045	0.24	1	-10000	0	1
tumor necrosis factor receptor activity	0	0	0.001	2	-10000	0	2
RPS6	0.026	0.022	-10000	0	-0.43	1	1
PPP5C	0.027	0.003	-10000	0	-10000	0	0
EIF4G1	0.027	0.002	-10000	0	-10000	0	0
IRS1	0.007	0.015	-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	-10000	0	-10000	0	0
EIF4EBP1	-0.076	0.31	-10000	0	-1	42	42
PIK3CA	0.027	0.002	-10000	0	-10000	0	0
PPP2R5D	-0.006	0.098	-10000	0	-0.39	25	25
peptide biosynthetic process	-0.007	0.033	0.18	12	-0.24	1	13
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	0.003	6	-10000	0	6
EEF2	-0.007	0.033	0.18	12	-0.24	1	13
eIF4E/4E-BP1	-0.059	0.29	-10000	0	-0.96	42	42

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.08	-10000	0	-0.23	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.026	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.029	0.074	0.3	1	-0.34	1	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.043	-10000	0	-0.24	3	3
antigen processing and presentation of peptide antigen via MHC class I	-0.005	0.055	-10000	0	-0.28	1	1
CaM/Ca2+	0.034	0.078	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.011	0.07	-10000	0	-0.37	1	1
AKT1	-0.008	0.057	-10000	0	-10000	0	0
MAP2K1	-0.015	0.062	0.29	1	-0.26	1	2
MAP3K11	-0.005	0.066	0.29	1	-10000	0	1
IFNGR1	0.022	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.023	0.14	-10000	0	-0.39	40	40
Rap1/GTP	0.001	0.055	-10000	0	-10000	0	0
CRKL/C3G	0.038	0.018	-10000	0	-0.28	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.034	0.089	-10000	0	-10000	0	0
CEBPB	0.017	0.14	0.28	2	-0.59	9	11
STAT3	0.027	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.042	0.11	-10000	0	-0.66	3	3
STAT1	-0.004	0.066	0.29	1	-0.37	1	2
CALM1	0.025	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.019	0.13	-10000	0	-0.42	44	44
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.01	0.069	0.29	1	-0.36	1	2
CEBPB/PTGES2/Cbp/p300	0.023	0.095	-10000	0	-0.38	6	6
mol:Ca2+	0.032	0.078	-10000	0	-0.22	1	1
MAPK3	-0.006	0.093	-10000	0	-0.74	3	3
STAT1 (dimer)	0.004	0.078	-10000	0	-0.39	1	1
MAPK1	-0.035	0.17	-10000	0	-0.73	22	22
JAK2	0.019	0.039	-10000	0	-0.4	3	3
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	0.022	0.019	-10000	0	-10000	0	0
CAMK2D	0.027	0.005	-10000	0	-10000	0	0
DAPK1	0.008	0.15	0.27	5	-0.56	23	28
SMAD7	0.002	0.033	0.13	1	-0.24	1	2
CBL/CRKL/C3G	0.02	0.071	0.29	1	-10000	0	1
PI3K	0.035	0.077	-10000	0	-10000	0	0
IFNG	-0.019	0.13	-10000	0	-0.42	44	44
apoptosis	0.002	0.13	0.25	4	-0.43	31	35
CAMK2G	0.027	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.027	0.004	-10000	0	-10000	0	0
CAMK2A	-0.008	0.11	-10000	0	-0.4	34	34
CAMK2B	-0.012	0.11	0.36	1	-0.4	34	35
FRAP1	-0.02	0.05	-10000	0	-10000	0	0
PRKCD	-0.008	0.061	0.28	1	-10000	0	1
RAP1B	0.027	0.002	-10000	0	-10000	0	0
negative regulation of cell growth	-0.005	0.055	-10000	0	-0.28	1	1
PTPN2	0.022	0.011	-10000	0	-10000	0	0
EP300	0.026	0.006	-10000	0	-10000	0	0
IRF1	-0.006	0.057	0.26	2	-10000	0	2
STAT1 (dimer)/PIASy	0.009	0.068	0.29	1	-0.36	1	2
SOCS1	0.017	0.093	-10000	0	-1	3	3
mol:GDP	0.017	0.068	0.27	1	-10000	0	1
CASP1	0.002	0.036	0.13	1	-0.27	1	2
PTGES2	0.027	0.003	-10000	0	-10000	0	0
IRF9	0.023	0.049	0.14	6	-0.18	1	7
mol:PI-3-4-5-P3	0.021	0.069	-10000	0	-10000	0	0
RAP1/GDP	0.019	0.064	-10000	0	-10000	0	0
CBL	-0.004	0.065	0.29	1	-10000	0	1
MAP3K1	-0.005	0.066	0.29	1	-0.24	1	2
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	0.055	-10000	0	-0.28	1	1
PTPN11	-0.004	0.065	-10000	0	-0.23	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.079	0.1	-10000	0	-0.54	1	1
UGCG	0.021	0.045	-10000	0	-0.58	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	0.011	0.13	-10000	0	-0.46	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.022	0.045	-10000	0	-0.58	2	2
mol:DAG	-0.004	0.12	-10000	0	-0.82	9	9
CaM/Ca2+/Calcineurin A alpha-beta B1	0.022	0.13	-10000	0	-0.41	25	25
FRAP1	0.013	0.14	-10000	0	-0.46	27	27
FOXO3	0.017	0.11	-10000	0	-0.42	11	11
AKT1	0.02	0.12	-10000	0	-0.42	15	15
GAB2	0.027	0.004	-10000	0	-10000	0	0
SMPD1	0.012	0.091	-10000	0	-0.64	8	8
SGMS1	0.012	0.093	-10000	0	-0.62	9	9
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	0.007	0.006	-10000	0	-10000	0	0
CALM1	0.025	0.007	-10000	0	-10000	0	0
cell proliferation	0.035	0.083	-10000	0	-0.41	7	7
EIF3A	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.043	0.01	-10000	0	-10000	0	0
RPS6KB1	0.015	0.1	-10000	0	-0.83	6	6
mol:sphingomyelin	-0.004	0.12	-10000	0	-0.82	9	9
natural killer cell activation	0	0.002	-10000	0	-0.011	2	2
JAK3	0.028	0.022	-10000	0	-0.42	1	1
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
JAK1	0.028	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
MYC	0.046	0.12	0.31	1	-0.44	4	5
MYB	0.031	0.064	-10000	0	-1.1	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.027	0.094	-10000	0	-0.43	8	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.043	0.098	-10000	0	-0.76	6	6
mol:PI-3-4-5-P3	0.025	0.094	-10000	0	-0.42	8	8
Rac1/GDP	0.021	0.013	-10000	0	-10000	0	0
T cell proliferation	0.025	0.081	-10000	0	-0.46	4	4
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	0.003	-10000	0	-0.065	1	1
PRKCZ	0.025	0.082	-10000	0	-0.48	4	4
NF kappa B1 p50/RelA	0.036	0.13	-10000	0	-0.44	18	18
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.026	0.056	-10000	0	-0.42	4	4
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
RELA	0.027	0.004	-10000	0	-10000	0	0
IL2RA	0.017	0.065	-10000	0	-0.4	11	11
IL2RB	0.018	0.063	-10000	0	-0.4	10	10
TERT	-0.014	0.13	0.36	2	-0.42	42	44
E2F1	0.033	0.041	-10000	0	-0.4	1	1
SOS1	0.028	0.003	-10000	0	-10000	0	0
RPS6	0.026	0.022	-10000	0	-0.43	1	1
mol:cAMP	-0.002	0.002	0.031	1	-10000	0	1
PTPN11	0.028	0.003	-10000	0	-10000	0	0
IL2RG	0.027	0.029	-10000	0	-0.4	2	2
actin cytoskeleton organization	0.025	0.081	-10000	0	-0.46	4	4
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL2	0.019	0.012	-10000	0	-10000	0	0
PIK3CA	0.029	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.047	0.024	-10000	0	-10000	0	0
LCK	0.019	0.063	-10000	0	-0.42	9	9
BCL2	-0.001	0.2	-10000	0	-0.8	23	23

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.022	0.035	-10000	0	-0.31	2	2
KLHL20	0.043	0.075	0.21	29	-0.23	7	36
CYFIP2	0.026	0.02	-10000	0	-0.4	1	1
Rac1/GDP	0.068	0.08	0.28	5	-10000	0	5
ENAH	0.022	0.035	-10000	0	-0.31	2	2
AP1M1	0.027	0.003	-10000	0	-10000	0	0
RAP1B	0.027	0.002	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.019	0.022	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.028	-10000	0	-0.16	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.049	0.056	-10000	0	-0.21	7	7
RAPGEF1	0.056	0.082	0.31	6	-10000	0	6
CTNND1	0.027	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.03	0.036	-10000	0	-0.31	3	3
CRK	0.056	0.076	-10000	0	-0.3	1	1
E-cadherin/gamma catenin/alpha catenin	0.053	0.018	-10000	0	-0.24	1	1
alphaE/beta7 Integrin	0.022	0.061	-10000	0	-0.26	18	18
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
NCKAP1	0.027	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.013	-10000	0	-10000	0	0
DLG1	0.022	0.036	-10000	0	-0.31	2	2
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.005	0.01	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.02	0.085	-10000	0	-0.23	42	42
PI3K	0.009	0.014	-10000	0	-10000	0	0
ARF6	0.025	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.039	0.016	-10000	0	-0.28	1	1
TIAM1	-0.012	0.12	-10000	0	-0.4	41	41
E-cadherin(dimer)/Ca2+	0.063	0.014	-10000	0	-10000	0	0
AKT1	0.032	0.041	0.14	1	-10000	0	1
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
CDH1	0.027	0.002	-10000	0	-10000	0	0
RhoA/GDP	0.081	0.081	0.28	7	-10000	0	7
actin cytoskeleton organization	0.04	0.061	0.17	31	-0.17	7	38
CDC42/GDP	0.075	0.08	0.27	6	-10000	0	6
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.02	0.012	-10000	0	-0.2	1	1
ITGB7	0.01	0.083	-10000	0	-0.4	18	18
RAC1	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.068	0.015	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.048	0.009	-10000	0	-10000	0	0
mol:GDP	0.072	0.088	0.3	6	-10000	0	6
CDC42/GTP/IQGAP1	0.033	0.017	-10000	0	-0.23	1	1
JUP	0.026	0.02	-10000	0	-0.4	1	1
p120 catenin/RhoA/GDP	0.089	0.081	0.29	6	-10000	0	6
RAC1/GTP/IQGAP1	0.032	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.039	0.016	-10000	0	-0.28	1	1
RHOA	0.027	0.004	-10000	0	-10000	0	0
CDC42	0.025	0.021	-10000	0	-0.4	1	1
CTNNA1	0.027	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.032	0.047	0.14	32	-0.16	3	35
NME1	0.019	0.066	0.36	1	-0.43	9	10
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.021	0.035	-10000	0	-0.3	3	3
regulation of cell-cell adhesion	0.012	0.016	-10000	0	-10000	0	0
WASF2	0.015	0.026	-10000	0	-10000	0	0
Rap1/GTP	0.08	0.071	0.29	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.058	0.058	-10000	0	-10000	0	0
CCND1	0.036	0.054	0.15	31	-0.2	3	34
VAV2	0.071	0.14	-10000	0	-0.63	10	10
RAP1/GDP	0.088	0.078	0.29	7	-10000	0	7
adherens junction assembly	0.021	0.034	-10000	0	-0.29	3	3
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.002	-10000	0	-10000	0	0
PIP5K1C	0.026	0.02	-10000	0	-0.4	1	1
regulation of heterotypic cell-cell adhesion	0.044	0.052	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.013	0.011	-10000	0	-0.15	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.014	0.031	-10000	0	-0.31	2	2
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.066	-10000	0	-0.36	9	9
E-cadherin/beta catenin/alpha catenin	0.054	0.01	-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	0.037	-10000	0	-0.31	3	3

×

Aurora A signaling

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
Aurora A/GADD45A	0.046	0.036	-10000	0	-10000	0	0
BIRC5	0.028	0.016	0.36	1	-10000	0	1
NFKBIA	0.005	0.012	0.25	1	-10000	0	1
CPEB1	-0.083	0.18	-10000	0	-0.4	107	107
AKT1	0.005	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	0.053	0.036	-10000	0	-10000	0	0
GADD45A	0.026	0.005	-10000	0	-10000	0	0
GSK3B	0.025	0.002	-10000	0	-10000	0	0
PAK1/Aurora A	0.048	0.036	-10000	0	-10000	0	0
MDM2	0.026	0.02	-10000	0	-0.4	1	1
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.011	0.026	0.27	4	-10000	0	4
TP53	0.013	0.012	-10000	0	-10000	0	0
DLG7	0.006	0.005	-10000	0	-10000	0	0
AURKAIP1	0.026	0.007	-10000	0	-10000	0	0
ARHGEF7	0.021	0.012	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.056	0.037	-10000	0	-10000	0	0
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	0.015	0.046	0.3	10	-10000	0	10
G2/M transition checkpoint	0.006	0.008	-10000	0	-10000	0	0
mRNA polyadenylation	-0.028	0.081	-10000	0	-0.2	65	65
Aurora A/CPEB	-0.028	0.082	-10000	0	-0.2	65	65
Aurora A/TACC1/TRAP/chTOG	0.069	0.041	-10000	0	-10000	0	0
BRCA1	0.027	0.004	-10000	0	-10000	0	0
centrosome duplication	0.047	0.036	-10000	0	-10000	0	0
regulation of centrosome cycle	0.052	0.035	-10000	0	-10000	0	0
spindle assembly	0.067	0.04	-10000	0	-10000	0	0
TDRD7	0.027	0.004	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.075	0.033	-10000	0	-10000	0	0
CENPA	0.011	0.01	-10000	0	-10000	0	0
Aurora A/PP2A	0.047	0.036	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.035	0.04	0.2	1	-10000	0	1
negative regulation of DNA binding	0.012	0.018	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.03	0.023	-10000	0	-0.28	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
Ajuba/Aurora A	0.006	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0.011	0.028	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.009	-10000	0	-10000	0	0
TACC1	0.023	0.01	-10000	0	-10000	0	0
TACC3	0.027	0.005	-10000	0	-10000	0	0
Aurora A/Antizyme1	0.067	0.034	-10000	0	-10000	0	0
Aurora A/RasGAP	0.047	0.036	-10000	0	-10000	0	0
OAZ1	0.027	0.004	-10000	0	-10000	0	0
RAN	0.027	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	0.02	-10000	0	-0.4	1	1
GIT1/beta-PIX/PAK1	0.041	0.028	-10000	0	-0.24	1	1
Importin alpha/Importin beta/TPX2	0.011	0.026	0.27	4	-10000	0	4
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.015	0.028	0.28	4	-10000	0	4
PAK1	0.027	0.003	-10000	0	-10000	0	0
CKAP5	0.027	0.004	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.026	0.006	-9999	-10000	0	0
Rac1/GDP	0.025	0.011	-9999	-10000	0	0
DOCK1	0.027	0.005	-9999	-10000	0	0
ITGA4	0.01	0.083	-9999	-0.4	18	18
RAC1	0.025	0.008	-9999	-10000	0	0
alpha4/beta7 Integrin	0.016	0.092	-9999	-0.31	32	32
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.023	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin	0.043	0.057	-9999	-0.24	18	18
alpha4/beta7 Integrin/Paxillin	0.025	0.075	-9999	-0.24	32	32
lamellipodium assembly	0.01	0.076	-9999	-0.41	10	10
PIK3CA	0.027	0.003	-9999	-10000	0	0
PI3K	0.039	0.008	-9999	-10000	0	0
ARF6	0.025	0.007	-9999	-10000	0	0
TLN1	0.027	0.004	-9999	-10000	0	0
PXN	0.014	0.002	-9999	-10000	0	0
PIK3R1	0.027	0.005	-9999	-10000	0	0
ARF6/GTP	0.045	0.048	-9999	-10000	0	0
cell adhesion	0.047	0.052	-9999	-10000	0	0
CRKL/CBL	0.039	0.009	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.035	0.052	-9999	-0.21	18	18
ITGB1	0.027	0.002	-9999	-10000	0	0
ITGB7	0.01	0.083	-9999	-0.4	18	18
ARF6/GDP	0.026	0.011	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.042	0.074	-9999	-0.39	8	8
p130Cas/Crk/Dock1	0.045	0.026	-9999	-0.24	1	1
VCAM1	0.016	0.065	-9999	-0.4	11	11
alpha4/beta1 Integrin/Paxillin/Talin	0.048	0.053	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.049	0.05	-9999	-10000	0	0
BCAR1	0.026	0.02	-9999	-0.4	1	1
mol:GDP	-0.047	0.05	-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	0.02	-9999	-0.4	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.048	0.053	-9999	-10000	0	0
Rac1/GTP	0.009	0.083	-9999	-0.45	10	10

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.023	0.027	-10000	0	-0.2	6	6
epithelial cell differentiation	0.057	0.013	-10000	0	-10000	0	0
CYFIP2	0.026	0.02	-10000	0	-0.4	1	1
ENAH	-0.01	0.026	-10000	0	-10000	0	0
EGFR	0.024	0.021	-10000	0	-0.4	1	1
EPHA2	0.025	0.022	-10000	0	-0.43	1	1
MYO6	0.013	0.011	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.054	0.016	-10000	0	-0.24	1	1
AQP5	-0.006	0.043	-10000	0	-10000	0	0
CTNND1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.012	0.015	0.18	2	-10000	0	2
regulation of calcium-dependent cell-cell adhesion	0.002	0.043	-10000	0	-10000	0	0
EGF	-0.062	0.17	-10000	0	-0.4	89	89
NCKAP1	0.027	0	-10000	0	-10000	0	0
AQP3	0.011	0.036	0.24	1	-0.43	1	2
cortical microtubule organization	0.057	0.013	-10000	0	-10000	0	0
GO:0000145	-0.008	0.015	0.16	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.062	0.014	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	-0.015	0.013	-10000	0	-10000	0	0
ARF6	0.025	0.007	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.03	-10000	0	-0.22	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.006	0.011	-10000	0	-10000	0	0
PVRL2	0.027	0.003	-10000	0	-10000	0	0
ZYX	0.012	0.009	-10000	0	-10000	0	0
ARF6/GTP	0.064	0.034	-10000	0	-10000	0	0
CDH1	0.027	0.002	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.001	0.093	-10000	0	-10000	0	0
RhoA/GDP	0.057	0.015	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.008	0.012	0.16	2	-10000	0	2
IGF-1R heterotetramer	0.026	0.006	-10000	0	-10000	0	0
GIT1	0.026	0.02	-10000	0	-0.4	1	1
IGF1R	0.026	0.006	-10000	0	-10000	0	0
IGF1	-0.079	0.18	-10000	0	-0.4	112	112
DIAPH1	0.042	0.092	-10000	0	-0.52	7	7
Wnt receptor signaling pathway	-0.057	0.013	-10000	0	-10000	0	0
RHOA	0.027	0.004	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.013	-10000	0	-10000	0	0
CTNNA1	0.027	0.004	-10000	0	-10000	0	0
VCL	-0.008	0.013	0.17	2	-10000	0	2
EFNA1	0.027	0.004	-10000	0	-10000	0	0
LPP	-0.01	0.016	-10000	0	-10000	0	0
Ephrin A1/EPHA2	0.047	0.021	-10000	0	-10000	0	0
SEC6/SEC8	0.014	0.006	-10000	0	-10000	0	0
MGAT3	0.002	0.043	-10000	0	-10000	0	0
HGF/MET	0.042	0.044	-10000	0	-10000	0	0
HGF	0.017	0.06	-10000	0	-0.4	9	9
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.027	-10000	0	-0.2	6	6
actin cable formation	0.01	0.052	0.21	12	-0.29	1	13
KIAA1543	-0.008	0.013	0.16	2	-10000	0	2
KIFC3	0.004	0.044	-10000	0	-10000	0	0
NCK1	0.027	0.002	-10000	0	-10000	0	0
EXOC3	0.027	0.004	-10000	0	-10000	0	0
ACTN1	0.012	0.012	-10000	0	-10000	0	0
NCK1/GIT1	0.039	0.017	-10000	0	-0.28	1	1
mol:GDP	0.057	0.013	-10000	0	-10000	0	0
EXOC4	0.027	0.005	-10000	0	-10000	0	0
STX4	0.013	0.011	-10000	0	-10000	0	0
PIP5K1C	0.012	0.015	0.18	2	-10000	0	2
LIMA1	0.022	0.049	-10000	0	-0.4	6	6
ABI1	0.027	0.002	-10000	0	-10000	0	0
ROCK1	-0.007	0.038	0.24	2	-10000	0	2
adherens junction assembly	0.003	0.037	0.27	1	-0.3	1	2
IGF-1R heterotetramer/IGF1	-0.009	0.1	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.007	-10000	0	-10000	0	0
MET	0.023	0.046	0.36	1	-0.43	4	5
PLEKHA7	0.013	0.011	0.18	2	-10000	0	2
mol:GTP	0.059	0.029	-10000	0	-0.22	2	2
establishment of epithelial cell apical/basal polarity	-0.003	0.049	0.32	3	-10000	0	3
cortical actin cytoskeleton stabilization	0.023	0.027	-10000	0	-0.2	6	6
regulation of cell-cell adhesion	-0.008	0.012	0.16	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.027	-10000	0	-0.2	6	6

×

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	-0.023	0.04	0.39	4	-10000	0	4
PI3K Class IB/PDE3B	0.023	0.04	-10000	0	-0.4	4	4
PDE3B	0.023	0.04	-10000	0	-0.4	4	4

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.036	0.034	-10000	0	-0.28	5	5
AKT1	0.089	0.089	0.35	10	-0.4	1	11
PTK2B	0.014	0.037	-10000	0	-0.49	1	1
VEGFR2 homodimer/Frs2	0.034	0.03	-10000	0	-0.58	1	1
CAV1	0.023	0.04	-10000	0	-0.4	4	4
CALM1	0.025	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.051	0.032	-10000	0	-0.53	1	1
endothelial cell proliferation	0.094	0.12	0.27	110	-10000	0	110
mol:Ca2+	0.013	0.022	-10000	0	-0.33	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.056	0.039	-10000	0	-0.51	1	1
RP11-342D11.1	0.011	0.029	-10000	0	-0.49	1	1
CDH5	0.027	0.001	-10000	0	-10000	0	0
VEGFA homodimer	0.064	0.025	0.26	1	-10000	0	1
SHC1	0.027	0.004	-10000	0	-10000	0	0
SHC2	0.018	0.062	-10000	0	-0.41	9	9
HRAS/GDP	0.046	0.032	-10000	0	-0.44	1	1
SH2D2A	0.027	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.096	0.083	0.29	5	-0.41	1	6
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.05	0.033	-10000	0	-0.53	1	1
VEGFR1 homodimer	0.021	0.012	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.073	0.04	-10000	0	-0.48	1	1
GRB10	0.021	0.03	-10000	0	-0.49	1	1
PTPN11	0.027	0.003	-10000	0	-10000	0	0
GRB2	0.027	0.004	-10000	0	-10000	0	0
PAK1	0.027	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.074	0.038	-10000	0	-0.49	1	1
HRAS	0.026	0.02	-10000	0	-0.4	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.004	0.077	-10000	0	-0.54	2	2
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	0.055	0.038	-10000	0	-0.5	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.023	0.04	-10000	0	-0.4	4	4
Nck/Pak	0.04	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.051	0.032	-10000	0	-0.53	1	1
mol:GDP	0.058	0.035	-10000	0	-0.46	1	1
mol:NADP	0.086	0.088	0.3	13	-0.4	1	14
eNOS/Hsp90	0.09	0.085	0.3	13	-0.36	1	14
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.013	0.022	-10000	0	-0.33	1	1
HIF1A/ARNT	0.036	0.019	-10000	0	-0.28	1	1
SHB	0.027	0.004	-10000	0	-10000	0	0
VEGFA	0.029	0.016	0.36	1	-10000	0	1
VEGFC	0.02	0.049	-10000	0	-0.4	6	6
FAK1/Vinculin	0.056	0.075	0.28	5	-0.57	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	0.042	-10000	0	-0.51	1	1
PTPN6	0.027	0.004	-10000	0	-10000	0	0
EPAS1	0.034	0.017	-10000	0	-0.31	1	1
mol:L-citrulline	0.086	0.088	0.3	13	-0.4	1	14
ITGAV	0.027	0.002	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.064	0.034	-10000	0	-0.51	1	1
VEGFR2 homodimer/VEGFA homodimer	0.052	0.034	-10000	0	-0.54	1	1
VEGFR2/3 heterodimer	0.032	0.039	-10000	0	-0.58	1	1
VEGFB	0.027	0.004	-10000	0	-10000	0	0
MAPK11	0.007	0.04	0.43	1	-0.53	1	2
VEGFR2 homodimer	0.02	0.032	-10000	0	-0.65	1	1
FLT1	0.021	0.012	-10000	0	-10000	0	0
NEDD4	0.027	0.007	-10000	0	-10000	0	0
MAPK3	0.033	0.08	0.3	4	-0.32	1	5
MAPK1	0.033	0.079	0.29	5	-0.32	1	6
VEGFA145/NRP2	0.04	0.028	0.26	1	-0.28	3	4
VEGFR1/2 heterodimer	0.026	0.033	-10000	0	-0.58	1	1
KDR	0.02	0.032	-10000	0	-0.66	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.052	0.038	-10000	0	-0.49	1	1
SRC	0.017	0.013	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.046	0.085	0.36	4	-0.33	1	5
PI3K	0.049	0.056	0.3	1	-0.41	1	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.051	0.032	-10000	0	-0.53	1	1
FES	0.022	0.032	-10000	0	-0.51	1	1
GAB1	0.03	0.037	-10000	0	-0.55	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.032	0.033	-10000	0	-0.36	1	1
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
SOS1	0.027	0.002	-10000	0	-10000	0	0
ARNT	0.026	0.02	-10000	0	-0.4	1	1
eNOS/Caveolin-1	0.088	0.084	0.33	6	-0.38	1	7
VEGFR2 homodimer/VEGFA homodimer/Yes	0.043	0.043	-10000	0	-0.71	1	1
PI3K/GAB1	0.053	0.054	0.27	1	-0.44	1	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.076	0.036	-10000	0	-0.49	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.041	0.051	-10000	0	-0.47	2	2
HSP90AA1	0.025	0.007	-10000	0	-10000	0	0
CDC42	0.022	0.031	-10000	0	-0.51	1	1
actin cytoskeleton reorganization	0.049	0.032	-10000	0	-0.53	1	1
PTK2	0.028	0.054	0.28	1	-0.6	1	2
EDG1	0.011	0.029	-10000	0	-0.49	1	1
mol:DAG	0.013	0.022	-10000	0	-0.33	1	1
CaM/Ca2+	0.022	0.028	-10000	0	-0.31	1	1
MAP2K3	0.012	0.034	-10000	0	-0.49	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.065	0.06	-10000	0	-0.51	1	1
PLCG1	0.013	0.022	-10000	0	-0.34	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.039	0.039	-10000	0	-0.34	1	1
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
YES1	0.022	0.022	-10000	0	-0.4	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.051	0.032	0.25	1	-0.53	1	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.05	0.032	-10000	0	-0.53	1	1
cell migration	0.063	0.08	0.28	8	-0.5	1	9
mol:PI-3-4-5-P3	0.054	0.055	0.29	1	-0.39	1	2
FYN	0.027	0.004	-10000	0	-10000	0	0
VEGFB/NRP1	0.027	0.029	-10000	0	-0.47	1	1
mol:NO	0.086	0.088	0.3	13	-0.4	1	14
PXN	0.027	0.002	-10000	0	-10000	0	0
HRAS/GTP	0.027	0.027	-10000	0	-0.44	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.04	0.034	-10000	0	-0.51	1	1
VHL	0.027	0.003	-10000	0	-10000	0	0
ITGB3	0.022	0.044	-10000	0	-0.4	5	5
NOS3	0.088	0.092	0.35	8	-0.44	1	9
VEGFR2 homodimer/VEGFA homodimer/Sck	0.045	0.049	-10000	0	-0.53	1	1
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	0.007	0.023	-10000	0	-10000	0	0
PRKCB	-0.01	0.055	-10000	0	-10000	0	0
VCL	0.027	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1	0.031	0.031	0.23	1	-0.49	1	2
VEGFR1/2 heterodimer/VEGFA homodimer	0.039	0.038	-10000	0	-0.53	1	1
VEGFA165/NRP2	0.04	0.028	0.26	1	-0.28	3	4
MAPKKK cascade	0.033	0.04	-10000	0	-0.44	1	1
NRP2	0.025	0.034	-10000	0	-0.4	3	3
VEGFC homodimer	0.02	0.049	-10000	0	-0.4	6	6
NCK1	0.027	0.002	-10000	0	-10000	0	0
ROCK1	0.022	0.022	-10000	0	-0.4	1	1
FAK1/Paxillin	0.056	0.076	0.28	5	-0.57	1	6
MAP3K13	0.023	0.03	-10000	0	-0.51	1	1
PDPK1	0.08	0.088	0.26	64	-0.35	1	65

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.049	0.049	-10000	0	-10000	0	0
TC10/GTP	0.034	0.045	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.076	0.027	-10000	0	-10000	0	0
HRAS	0.026	0.02	-10000	0	-0.4	1	1
APS homodimer	0.024	0.041	0.36	1	-0.43	3	4
GRB14	-0.007	0.11	-10000	0	-0.4	31	31
FOXO3	-0.009	0.14	-10000	0	-0.57	27	27
AKT1	-0.003	0.06	0.24	2	-10000	0	2
INSR	0.039	0.015	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.075	0.069	-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	0.016	0.065	-10000	0	-0.4	11	11
CRK	0.023	0.01	-10000	0	-10000	0	0
PTPN1	0.006	0.023	0.31	1	-10000	0	1
CAV1	0.014	0.044	0.19	9	-0.21	2	11
CBL/APS/CAP/Crk-II/C3G	0.054	0.059	0.26	1	-10000	0	1
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	0.022	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.065	0.066	-10000	0	-0.29	1	1
RPS6KB1	-0.007	0.055	0.23	2	-10000	0	2
PARD6A	0.023	0.043	-10000	0	-0.43	4	4
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	0.009	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.029	0.057	-10000	0	-10000	0	0
HRAS/GTP	0.021	0.015	-10000	0	-10000	0	0
Insulin Receptor	0.039	0.015	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.084	0.032	-10000	0	-10000	0	0
PRKCI	0.027	0.056	-10000	0	-0.41	3	3
Insulin Receptor/Insulin/GRB14/PDK1	0.022	0.057	-10000	0	-10000	0	0
SHC1	0.027	0.004	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.042	0.03	-10000	0	-0.35	1	1
PI3K	0.072	0.026	-10000	0	-10000	0	0
NCK2	0.027	0	-10000	0	-10000	0	0
RHOQ	0.027	0.003	-10000	0	-10000	0	0
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.014	-10000	0	-0.28	1	1
AKT2	-0.003	0.061	0.24	2	-10000	0	2
PRKCZ	0.017	0.075	-10000	0	-0.4	2	2
SH2B2	0.024	0.041	0.36	1	-0.43	3	4
SHC/SHIP	0.044	0.033	0.29	1	-10000	0	1
F2RL2	-0.008	0.12	-10000	0	-0.43	34	34
TRIP10	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.059	0.025	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.084	0.032	-10000	0	-10000	0	0
RAPGEF1	0.026	0.02	-10000	0	-0.4	1	1
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.002	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.047	0.055	0.26	1	-0.23	2	3
TC10/GDP	0.02	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.067	0.034	-10000	0	-10000	0	0
INPP5D	0.016	0.043	0.19	9	-10000	0	9
SOS1	0.027	0.002	-10000	0	-10000	0	0
SGK1	-0.029	0.18	-10000	0	-0.75	27	27
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.003	-10000	0	-10000	0	0
IRS1	0.027	0.002	-10000	0	-10000	0	0
p62DOK/RasGAP	0.042	0.03	-10000	0	-0.35	1	1
INS	0.028	0.014	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.016	0.043	0.19	9	-10000	0	9
GRB2	0.027	0.004	-10000	0	-10000	0	0
EIF4EBP1	-0.009	0.052	0.2	1	-10000	0	1
PTPRA	0.028	0.016	-10000	0	-10000	0	0
PIK3CA	0.027	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.036	0.006	-10000	0	-10000	0	0
PDPK1	0.027	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.036	0.018	-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	0.038	0.08	-10000	0	-0.22	36	36

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.035	0.014	-10000	0	-0.23	1	1
ATM	0.027	0.004	-10000	0	-10000	0	0
MAP2K3	0.01	0.071	0.19	1	-0.39	5	6
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.017	0.063	0.23	1	-0.4	4	5
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.026	0.033	0.36	1	-0.41	2	3
TXN	0.007	0.001	-10000	0	-10000	0	0
CALM1	0.025	0.007	-10000	0	-10000	0	0
GADD45A	0.026	0.005	-10000	0	-10000	0	0
GADD45B	0.027	0.004	-10000	0	-10000	0	0
MAP3K1	0.026	0.02	-10000	0	-0.4	1	1
MAP3K6	0.025	0.021	-10000	0	-0.4	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	0.019	-10000	0	-0.28	1	1
TAK1/TAB family	-0.001	0.016	-10000	0	-0.14	1	1
RAC1/OSM/MEKK3	0.045	0.022	-10000	0	-0.21	1	1
TRAF2	0.026	0.02	-10000	0	-0.4	1	1
RAC1/OSM/MEKK3/MKK3	0.02	0.063	-10000	0	-0.31	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	-0.012	0.11	0.36	1	-0.4	34	35
CCM2	0.024	0.021	-10000	0	-0.4	1	1
CaM/Ca2+/CAMKIIB	0.011	0.072	0.23	1	-0.23	34	35
MAPK11	0.024	0.031	-10000	0	-0.43	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.024	0.07	0.24	1	-0.21	33	34
OSM/MEKK3	0.035	0.02	-10000	0	-0.28	1	1
TAOK1	0.014	0.003	-10000	0	-10000	0	0
TAOK2	0.015	0.003	-10000	0	-10000	0	0
TAOK3	0.015	0.002	-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	0.027	0.004	-10000	0	-10000	0	0
MAP3K3	0.027	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.025	0.009	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.059	0.027	0.24	1	-0.21	2	3

×

Arf1 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
coatomer protein complex	0.057	0.071	0.15	122	-0.31	1	123
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.01	0.034	0.14	9	-0.17	1	10
AP2	0.039	0.016	-10000	0	-0.28	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.032	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	0.011	0.081	-10000	0	-0.4	17	17
CLTA	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
ARFGAP1	0.004	0.018	0.27	1	-0.28	1	2
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	0.016	0.19	1	-0.25	1	2
mol:Choline	0.005	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	0.017	0.18	1	-0.23	1	2
AP2M1	0.027	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	1	-0.2	1	2
ARFIP2	0.016	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	0.019	-10000	0	-10000	0	0
ARF1/GTP/ARHGAP10	0.02	0.005	-10000	0	-10000	0	0
GGA3	0.027	0.004	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.025	0.026	-10000	0	-0.24	4	4
AP2A1	0.026	0.02	-10000	0	-0.4	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.018	0.14	1	-0.21	1	2
ARF1/GDP/Membrin	0.018	0.033	-10000	0	-0.28	4	4
Arfaptin 2/Rac/GDP	0.031	0.013	-10000	0	-10000	0	0
CYTH2	0.029	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.037	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.018	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	0.018	0.04	-10000	0	-10000	0	0
PLD2	0.006	0.007	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.004	0.018	0.27	1	-0.28	1	2
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	0.004	0.018	0.27	1	-0.28	1	2
GOSR2	0.011	0.016	-10000	0	-0.31	1	1
USO1	0.009	0.031	-10000	0	-0.31	4	4
GBF1	0.008	0.034	-10000	0	-0.31	5	5
ARF1/GTP/Arfaptin 2	0.037	0.009	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.042	0.058	-10000	0	-0.24	18	18

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.023	0.043	-9999	-0.43	4	4
PLK4	0.026	0.006	-9999	-10000	0	0
regulation of centriole replication	0.01	0.03	-9999	-0.3	4	4

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.025	0.028	-9999	-0.4	2	2
positive regulation of NF-kappaB transcription factor activity	0.029	0.027	-9999	-0.28	2	2
MAP2K4	0.018	0.025	-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	0.043	-9999	-0.34	6	6
IKBKG	0.026	0.02	-9999	-0.4	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.021	0.012	-9999	-10000	0	0
TRAIL/TRAILR2	0.03	0.027	-9999	-0.28	2	2
TRAIL/TRAILR3	0.008	0.085	-9999	-0.3	30	30
TRAIL/TRAILR1	0.03	0.027	-9999	-0.28	2	2
TRAIL/TRAILR4	0.03	0.027	-9999	-0.28	2	2
TRAIL/TRAILR1/DAP3/GTP	0.038	0.029	-9999	-0.21	2	2
IKK complex	0.02	0.043	-9999	-0.34	2	2
RIPK1	0.027	0.003	-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	0.012	0.024	-9999	-0.28	3	3
MAP3K1	0.021	0.029	-9999	-10000	0	0
TRAILR4 (trimer)	0.021	0.012	-9999	-10000	0	0
TRADD	0.027	0.002	-9999	-10000	0	0
TRAILR1 (trimer)	0.021	0.012	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.022	0.023	-9999	-10000	0	0
CFLAR	0.027	0	-9999	-10000	0	0
MAPK1	0.012	0.014	-9999	-0.28	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	0.059	0.04	-9999	-10000	0	0
mol:ceramide	0.007	0.043	-9999	-0.34	6	6
FADD	0.027	0.004	-9999	-10000	0	0
MAPK8	0.015	0.028	-9999	-10000	0	0
TRAF2	0.026	0.02	-9999	-0.4	1	1
TRAILR3 (trimer)	-0.007	0.11	-9999	-0.43	28	28
CHUK	0.026	0.006	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0.04	0.031	-9999	-0.24	2	2
DAP3	0.027	0.004	-9999	-10000	0	0
CASP10	0.006	0.02	-9999	-0.26	2	2
JNK cascade	0.029	0.027	-9999	-0.28	2	2
TRAIL (trimer)	0.025	0.028	-9999	-0.4	2	2
TNFRSF10C	-0.007	0.11	-9999	-0.43	28	28
TRAIL/TRAILR1/DAP3/GTP/FADD	0.047	0.033	-9999	-0.2	2	2
TRAIL/TRAILR2/FADD	0.04	0.031	-9999	-0.24	2	2
cell death	0.007	0.043	-9999	-0.34	6	6
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.022	0.023	-9999	-10000	0	0
TRAILR2 (trimer)	0.021	0.012	-9999	-10000	0	0
CASP8	0.014	0.027	-9999	-0.48	1	1
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.059	0.04	-9999	-10000	0	0

×

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	0.003	-10000	0	-10000	0	0
ELF1	0.02	0.045	-10000	0	-0.32	7	7
CCNA2	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.028	0.002	-10000	0	-10000	0	0
JAK3	0.027	0.022	-10000	0	-0.43	1	1
PIK3R1	0.027	0.005	-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	0.093	-10000	0	-0.47	6	6
SHC1	0.027	0.004	-10000	0	-10000	0	0
SP1	0.029	0.037	-10000	0	-0.32	5	5
IL2RA	0.005	0.084	-10000	0	-0.66	7	7
IL2RB	0.017	0.063	-10000	0	-0.4	10	10
SOS1	0.028	0.002	-10000	0	-10000	0	0
IL2RG	0.026	0.028	-10000	0	-0.4	2	2
G1/S transition of mitotic cell cycle	0.023	0.088	0.3	1	-0.65	5	6
PTPN11	0.028	0.003	-10000	0	-10000	0	0
CCND2	0.013	0.064	-10000	0	-0.66	4	4
LCK	0.018	0.063	-10000	0	-0.42	9	9
GRB2	0.027	0.004	-10000	0	-10000	0	0
IL2	0.02	0.007	-10000	0	-10000	0	0
CDK6	0.026	0.006	-10000	0	-10000	0	0
CCND3	0.04	0.088	0.34	1	-0.71	1	2

×

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	0.053	0.077	0.22	25	-0.27	1	26
ERC1	0.027	0.004	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.054	-10000	0	-0.3	11	11
NFKBIA	0.013	0.006	-10000	0	-10000	0	0
BIRC2	0.027	0.005	-10000	0	-10000	0	0
IKBKB	0.024	0.009	-10000	0	-10000	0	0
RIPK2	0.023	0.01	-10000	0	-10000	0	0
IKBKG	0.028	0.047	-10000	0	-0.34	3	3
IKK complex/A20	0.054	0.061	-10000	0	-0.33	2	2
NEMO/A20/RIP2	0.023	0.01	-10000	0	-10000	0	0
XPO1	0.027	0.001	-10000	0	-10000	0	0
NEMO/ATM	0.046	0.057	0.27	1	-0.33	4	5
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.027	0.002	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.037	0.004	-10000	0	-10000	0	0
IKK complex/ELKS	0.044	0.052	-10000	0	-0.32	2	2
BCL10/MALT1/TRAF6	0.04	0.031	-10000	0	-0.24	2	2
NOD2	0.015	0.073	-10000	0	-0.42	12	12
NFKB1	0.029	0.005	-10000	0	-10000	0	0
RELA	0.029	0.004	-10000	0	-10000	0	0
MALT1	0.02	0.023	-10000	0	-0.4	1	1
cIAP1/UbcH5C	0.039	0.009	-10000	0	-10000	0	0
ATM	0.027	0.004	-10000	0	-10000	0	0
TNF/TNFR1A	0.038	0.022	-10000	0	-0.28	2	2
TRAF6	0.027	0.004	-10000	0	-10000	0	0
PRKCA	0.026	0.006	-10000	0	-10000	0	0
CHUK	0.026	0.006	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
TNF	0.025	0.029	-10000	0	-0.4	2	2
NF kappa B1 p50/RelA	0.06	0.015	-10000	0	-10000	0	0
BCL10	0.026	0.021	-10000	0	-0.4	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.006	-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	0.055	-10000	0	-0.32	4	4
CYLD	0.026	0.02	-10000	0	-0.4	1	1
IKK complex/PKC alpha	0.053	0.058	-10000	0	-0.35	1	1

×

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	0.059	0.042	-10000	0	-0.26	2	2
Ran/GTP/Exportin 1/HDAC1	-0.007	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.05	0.18	1	-0.25	2	3
SUMO1	0.026	0.028	-10000	0	-0.4	2	2
ZFPM1	0.018	0.064	-10000	0	-0.43	9	9
NPC/RanGAP1/SUMO1/Ubc9	0.014	0.013	-10000	0	-0.18	2	2
FKBP3	0.024	0.021	-10000	0	-0.4	1	1
Histones	0.061	0.035	-10000	0	-10000	0	0
YY1/LSF	0.01	0.07	-10000	0	-0.32	5	5
SMG5	0.027	0.004	-10000	0	-10000	0	0
RAN	0.027	0.002	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.025	0.018	-10000	0	-0.2	2	2
I kappa B alpha/HDAC1	0.026	0.046	-10000	0	-10000	0	0
SAP18	0.022	0.011	-10000	0	-10000	0	0
RELA	0.025	0.023	-10000	0	-0.18	2	2
HDAC1/Smad7	0.04	0.028	-10000	0	-0.24	1	1
RANGAP1	0.026	0.006	-10000	0	-10000	0	0
HDAC3/TR2	0.036	0.03	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.019	0.039	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.054	0.19	1	-0.25	5	6
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.017	0.065	-10000	0	-0.4	11	11
GATA1	0.011	0.022	-10000	0	-10000	0	0
Mad/Max	0.036	0.024	-10000	0	-0.28	2	2
NuRD/MBD3 Complex/GATA1/Fog1	0.012	0.068	-10000	0	-0.32	4	4
RBBP7	0.027	0.003	-10000	0	-10000	0	0
NPC	0.016	0	-10000	0	-10000	0	0
RBBP4	0.026	0.006	-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	0.014	-10000	0	-10000	0	0
KAT2B	0.011	0.081	-10000	0	-0.4	17	17
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	0.032	-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	0.026	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.022	0.011	-10000	0	-10000	0	0
YY1/HDAC3	0.013	0.058	-10000	0	-0.31	4	4
YY1/HDAC2	0.011	0.069	-10000	0	-0.32	5	5
YY1/HDAC1	0.011	0.067	-10000	0	-0.32	5	5
NuRD/MBD2 Complex (MeCP1)	0.016	0.046	-10000	0	-0.44	2	2
PPARG	0.021	0.036	-10000	0	-0.25	5	5
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	0.031	-10000	0	-10000	0	0
MBD3L2	-0.018	0.002	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.028	-10000	0	-0.24	1	1
CREBBP	0.027	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.011	0.071	-10000	0	-0.32	6	6
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC3	0.023	0.013	-10000	0	-10000	0	0
HDAC2	0.027	0.004	-10000	0	-10000	0	0
YY1	0.008	0.054	-10000	0	-0.26	17	17
HDAC8	0.027	0.002	-10000	0	-10000	0	0
SMAD7	0.02	0.023	-10000	0	-0.4	1	1
NCOR2	0.026	0.02	-10000	0	-0.4	1	1
MXD1	0.025	0.028	-10000	0	-0.4	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	0.027	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.025	0.069	-10000	0	-0.31	4	4
YY1/SAP30/HDAC1	0.025	0.066	-10000	0	-0.29	5	5
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	0.014	-10000	0	-10000	0	0
histone deacetylation	0.016	0.046	-10000	0	-0.44	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.031	0.018	-10000	0	-10000	0	0
nuclear export	-0.053	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	0.03	0.046	-10000	0	-10000	0	0
GATA1/HDAC1	0.036	0.01	-10000	0	-10000	0	0
GATA1/HDAC3	0.034	0.028	-10000	0	-10000	0	0
CHD4	0.027	0.004	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.038	0.022	-10000	0	-0.28	2	2
SIN3/HDAC complex/Mad/Max	0.033	0.046	-10000	0	-0.33	2	2
NuRD Complex	-0.006	0.092	-10000	0	-0.3	19	19
positive regulation of chromatin silencing	0.059	0.034	-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	0.026	0.006	-10000	0	-10000	0	0
XPO1	0.027	0.001	-10000	0	-10000	0	0
SUMO1/HDAC1	0.038	0.033	-10000	0	-0.27	2	2
HDAC complex	0.065	0.019	-10000	0	-10000	0	0
GATA1/Fog1	0.03	0.049	-10000	0	-0.31	9	9
FKBP25/HDAC1/HDAC2	0.048	0.023	-10000	0	-0.24	1	1
TNF	0.025	0.029	-10000	0	-0.4	2	2
negative regulation of cell growth	0.033	0.046	-10000	0	-0.33	2	2
NuRD/MBD2/PRMT5 Complex	0.016	0.046	-10000	0	-0.44	2	2
Ran/GTP/Exportin 1	0.038	0.032	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.02	0.04	-10000	0	-0.26	2	2
SIN3/HDAC complex/NCoR1	0.008	0.058	-10000	0	-0.31	10	10
TFCP2	0.026	0.02	-10000	0	-0.4	1	1
NR2C1	0.027	0.003	-10000	0	-10000	0	0
MBD3	0.026	0.02	-10000	0	-0.4	1	1
MBD2	0.021	0.012	-10000	0	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	0.039	0.007	-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	0.053	0.056	0.21	6	-10000	0	6
NFKBIA	0.045	0.055	-10000	0	-0.18	1	1
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	0.027	0.004	-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	0.003	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.018	0.008	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-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	0.037	0.044	-10000	0	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.045	0.055	0.2	6	-10000	0	6
SRC	0.017	0.013	-10000	0	-10000	0	0
PI3K	0.039	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.037	0.045	-10000	0	-0.18	1	1
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	0.056	0.059	0.21	6	-10000	0	6
cell death	0.043	0.053	0.19	6	-10000	0	6
NF kappa B1 p105/c-Rel	0.026	0.011	-10000	0	-10000	0	0
LCK	0.017	0.063	-10000	0	-0.42	9	9
BCL3	0.027	0.003	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.02	0.012	-10000	0	-10000	0	0
SMAD2	0.012	0.032	-10000	0	-10000	0	0
SMAD3	0.019	0.018	-10000	0	-10000	0	0
SMAD3/SMAD4	0.026	0.058	-10000	0	-0.43	6	6
SMAD4/Ubc9/PIASy	0.041	0.025	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.04	0.048	-10000	0	-10000	0	0
PPM1A	0.026	0.007	-10000	0	-10000	0	0
CALM1	0.025	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	0.016	0.025	-10000	0	-10000	0	0
MAP3K1	0.026	0.02	-10000	0	-0.4	1	1
TRAP-1/SMAD4	0.03	0.018	-10000	0	-10000	0	0
MAPK3	0.026	0.02	-10000	0	-0.4	1	1
MAPK1	0.026	0.006	-10000	0	-10000	0	0
NUP214	0.027	0.003	-10000	0	-10000	0	0
CTDSP1	0.027	0.001	-10000	0	-10000	0	0
CTDSP2	0.027	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	-10000	0	-10000	0	0
UBE2I	0.027	0.004	-10000	0	-10000	0	0
NUP153	0.027	0.004	-10000	0	-10000	0	0
KPNA2	0.028	0.016	0.36	1	-10000	0	1
PIAS4	0.027	0.004	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	0.024	0.02	-10000	0	-10000	0	0
ATM	0.027	0.004	-10000	0	-10000	0	0
UBE2D3	0.027	0.005	-10000	0	-10000	0	0
PRKDC	0.024	0.009	-10000	0	-10000	0	0
ATR	0.027	0.002	-10000	0	-10000	0	0
UBE2L3	0.026	0.006	-10000	0	-10000	0	0
FANCD2	0.021	0.014	-10000	0	-0.27	1	1
protein ubiquitination	0.071	0.024	-10000	0	-10000	0	0
XRCC5	0.027	0.001	-10000	0	-10000	0	0
XRCC6	0.026	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.045	0.026	-10000	0	-0.24	1	1
MRE11A	0.027	0.004	-10000	0	-10000	0	0
DNA-PK	0.046	0.021	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.031	0.046	-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	0.031	0.36	2	-0.43	1	3
CDK2/Cyclin E1	0.04	0.023	0.26	2	-0.3	1	3
FANCG	0.027	0.004	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.04	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	0.022	0.022	-10000	0	-0.4	1	1
FANCA	0.027	0.003	-10000	0	-10000	0	0
DNA repair	0.047	0.064	0.26	5	-10000	0	5
BRCA1/BARD1/ubiquitin	0.04	0.005	-10000	0	-10000	0	0
BARD1/DNA-PK	0.059	0.027	-10000	0	-10000	0	0
FANCL	0.027	0.001	-10000	0	-10000	0	0
mRNA polyadenylation	-0.024	0.02	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.043	-10000	0	-0.26	4	4
BRCA1/BACH1/BARD1/TopBP1	0.055	0.009	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.057	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	0.027	0.001	-10000	0	-10000	0	0
PCNA	0.022	0.011	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.053	0.012	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.052	0.014	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.054	0.03	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	0.059	0.037	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.04	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.036	0.023	-10000	0	-10000	0	0
FA complex	0.031	0.016	-10000	0	-10000	0	0
BARD1/EWS	0.039	0.009	-10000	0	-10000	0	0
RBBP8	0.01	0.015	-10000	0	-0.28	1	1
TP53	0.022	0.011	-10000	0	-10000	0	0
TOPBP1	0.027	0.002	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.055	0.027	-10000	0	-10000	0	0
BRCA1/BARD1	0.078	0.026	0.26	2	-10000	0	2
CSTF1	0.016	0.014	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.02	0.001	-10000	0	-10000	0	0
CDK2	0.027	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	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.04	0.005	-10000	0	-10000	0	0
EWSR1	0.026	0.006	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.054	0.014	-10000	0	-10000	0	0
CLOCK	0.029	0.006	-10000	0	-10000	0	0
TIMELESS/CRY2	0.039	0.012	-10000	0	-10000	0	0
DEC1/BMAL1	0.031	0.043	-10000	0	-0.3	7	7
ATR	0.027	0.002	-10000	0	-10000	0	0
NR1D1	0.023	0.01	-10000	0	-10000	0	0
ARNTL	0.029	0.005	-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	0.004	-10000	0	-10000	0	0
mol:CO	-0.009	0.004	0.066	1	-10000	0	1
CHEK1	0.027	0.004	-10000	0	-10000	0	0
mol:HEME	0.009	0.004	-10000	0	-0.066	1	1
PER1	0.022	0.022	-10000	0	-0.4	1	1
BMAL/CLOCK/NPAS2	0.064	0.015	-10000	0	-10000	0	0
BMAL1/CLOCK	0.023	0.046	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.054	0.014	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.055	0.014	-10000	0	-10000	0	0
mol:NADPH	0.009	0.004	-10000	0	-0.066	1	1
PER1/TIMELESS	0.033	0.02	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.009	0.057	-10000	0	-0.43	7	7

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.027	0.004	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.041	0.027	-9999	-0.21	2	2
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.01	0.016	-9999	-0.3	1	1
AURKB	0.023	0.011	-9999	-10000	0	0
AURKC	0.023	0.03	-9999	-0.4	2	2

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.006	0.01	-10000	0	-10000	0	0
MDM2/SUMO1	0.037	0.04	-10000	0	-0.36	2	2
HDAC4	0.027	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.006	0.009	-10000	0	-10000	0	0
SUMO1	0.026	0.028	-10000	0	-0.4	2	2
NPC/RanGAP1/SUMO1	0.012	0.013	-10000	0	-0.18	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.01	0.012	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.027	0.002	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.037	0.036	-10000	0	-0.27	2	2
SUMO1/HDAC1	0.038	0.033	-10000	0	-0.27	2	2
RANGAP1	0.026	0.006	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.052	0.04	-10000	0	-0.31	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.014	0.013	-10000	0	-0.18	2	2
Ran/GTP	0.025	0.028	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.026	0.02	-10000	0	-0.4	1	1
UBE2I	0.027	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.029	0.19	1	-10000	0	1
NPC	0.016	0	-10000	0	-10000	0	0
PIAS2	0.021	0.012	-10000	0	-10000	0	0
PIAS1	0.026	0.006	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.012	0.019	-10000	0	-10000	0	0
adherens junction organization	0.036	0.039	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.025	-10000	0	-10000	0	0
FMN1	0.036	0.034	-10000	0	-10000	0	0
mol:IP3	0.013	0.018	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.043	0.036	-10000	0	-10000	0	0
CTNNB1	0.028	0.004	-10000	0	-10000	0	0
AKT1	0.052	0.047	0.18	4	-10000	0	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.062	0.064	-10000	0	-0.48	1	1
CTNND1	0.03	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.038	0.036	-10000	0	-10000	0	0
VASP	0.037	0.035	-10000	0	-10000	0	0
ZYX	0.037	0.035	-10000	0	-10000	0	0
JUB	0.039	0.035	-10000	0	-10000	0	0
EGFR(dimer)	0.05	0.041	-10000	0	-10000	0	0
E-cadherin/beta catenin-gamma catenin	0.05	0.017	-10000	0	-0.22	1	1
mol:PI-3-4-5-P3	0.085	0.059	0.21	5	-10000	0	5
PIK3CA	0.031	0.005	-10000	0	-10000	0	0
PI3K	0.087	0.06	0.22	5	-10000	0	5
FYN	-0.005	0.048	-10000	0	-0.32	1	1
mol:Ca2+	0.013	0.017	-10000	0	-10000	0	0
JUP	0.027	0.02	-10000	0	-0.4	1	1
PIK3R1	0.03	0.007	-10000	0	-10000	0	0
mol:DAG	0.013	0.018	-10000	0	-10000	0	0
CDH1	0.028	0.002	-10000	0	-10000	0	0
RhoA/GDP	0.023	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	0.013	-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	0.021	-10000	0	-0.4	1	1
CASR	-0.007	0.048	-10000	0	-10000	0	0
RhoA/GTP	0.02	0.024	-10000	0	-10000	0	0
AKT2	0.056	0.047	0.18	4	-10000	0	4
actin cable formation	0.033	0.034	-10000	0	-10000	0	0
apoptosis	-0.047	0.046	-10000	0	-0.18	3	3
CTNNA1	0.03	0.005	-10000	0	-10000	0	0
mol:GDP	0.01	0.018	-10000	0	-10000	0	0
PIP5K1A	0.037	0.035	-10000	0	-10000	0	0
PLCG1	0.013	0.018	-10000	0	-10000	0	0
Rac1/GTP	0.055	0.042	-10000	0	-10000	0	0
homophilic cell adhesion	0.002	0.003	-10000	0	-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	0.053	0.018	-9999	-0.24	1	1
E-cadherin/beta catenin	0.04	0.005	-9999	-10000	0	0
CTNNB1	0.027	0.003	-9999	-10000	0	0
JUP	0.026	0.02	-9999	-0.4	1	1
CDH1	0.027	0.002	-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	0.038	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	0.026	0.006	-9999	-9999
NF kappa B2 p100/RelB	0.075	0.023	-9999	-9999
NFKB1	0.027	0.005	-9999	-9999
MAP3K14	0.027	0.004	-9999	-9999
NF kappa B1 p50/RelB	0.039	0.008	-9999	-9999
RELB	0.027	0.003	-9999	-9999
NFKB2	0.026	0.006	-9999	-9999
NF kappa B2 p52/RelB	0.035	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	0.027	0.027	0.027	0.027
105_BMP4	0.027	0	0	0.027
105_BMP6	0.027	0.027	-0.4	0.027
105_BMP7	-0.4	0.027	0.027	0.36
105_BMP2	0.027	0.027	0	-0.4
131_RELN/VLDLR	-0.23	-0.23	-0.046	-0.24
30_TGFB1/TGF beta receptor Type II	0.027	0.027	0.029	0.031
84_STAT5B	0.0084	0.028	0	0.038
84_STAT5A	0.0084	0.028	0	0.038