PARADIGM pathway analysis of mRNASeq expression data - Head and Neck Squamous Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	234
Syndecan-1-mediated signaling events	199
IL4-mediated signaling events	142
Syndecan-4-mediated signaling events	138
Osteopontin-mediated events	109
HIF-1-alpha transcription factor network	101
Glypican 2 network	89
amb2 Integrin signaling	75
IL23-mediated signaling events	75
Syndecan-2-mediated signaling events	70

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	0.4500	234	1873	8	-0.34	0.15	1000	-1000	-0.024	-1000
Syndecan-1-mediated signaling events	0.3827	199	6798	34	-0.71	0.014	1000	-1000	-0.081	-1000
IL4-mediated signaling events	0.2731	142	12952	91	-1.4	1.2	1000	-1000	-0.2	-1000
Syndecan-4-mediated signaling events	0.2654	138	9286	67	-0.68	0.09	1000	-1000	-0.12	-1000
Osteopontin-mediated events	0.2096	109	4142	38	-0.44	0.014	1000	-1000	-0.13	-1000
HIF-1-alpha transcription factor network	0.1942	101	7737	76	-1	0.022	1000	-1000	-0.22	-1000
Glypican 2 network	0.1712	89	356	4	-0.15	-0.15	1000	-1000	-0.052	-1000
amb2 Integrin signaling	0.1442	75	6231	82	-0.58	0.014	1000	-1000	-0.11	-1000
IL23-mediated signaling events	0.1442	75	4515	60	-0.73	0.014	1000	-1000	-0.2	-1000
Syndecan-2-mediated signaling events	0.1346	70	4856	69	-0.42	0.022	1000	-1000	-0.066	-1000
TCGA08_p53	0.1327	69	488	7	-0.26	0.13	1000	-1000	-0.018	-1000
Endothelins	0.1135	59	5752	96	-0.56	0.016	1000	-1000	-0.099	-1000
p75(NTR)-mediated signaling	0.0942	49	6140	125	-0.53	0.014	1000	-1000	-0.12	-1000
FOXA2 and FOXA3 transcription factor networks	0.0827	43	2023	46	-0.5	0.021	1000	-1000	-0.14	-1000
Visual signal transduction: Rods	0.0827	43	2277	52	-0.42	0.014	1000	-1000	-0.11	-1000
Effects of Botulinum toxin	0.0808	42	1115	26	-0.22	0.014	1000	-1000	-0.074	-1000
Calcium signaling in the CD4+ TCR pathway	0.0750	39	1224	31	-0.48	0.014	1000	-1000	-0.11	-1000
Glypican 1 network	0.0712	37	1804	48	-0.37	0.033	1000	-1000	-0.061	-1000
Coregulation of Androgen receptor activity	0.0692	36	2757	76	-0.5	0.041	1000	-1000	-0.055	-1000
Signaling events mediated by the Hedgehog family	0.0692	36	1920	52	-0.45	0.064	1000	-1000	-0.083	-1000
BMP receptor signaling	0.0692	36	2991	81	-0.34	0.047	1000	-1000	-0.11	-1000
Caspase cascade in apoptosis	0.0673	35	2654	74	-0.14	0.049	1000	-1000	-0.062	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0673	35	2417	68	-0.53	0.038	1000	-1000	-0.16	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0673	35	2796	78	-0.15	0.039	1000	-1000	-0.091	-1000
Signaling events regulated by Ret tyrosine kinase	0.0654	34	2800	82	-0.18	0.014	1000	-1000	-0.1	-1000
PDGFR-beta signaling pathway	0.0654	34	3316	97	-0.12	0.014	1000	-1000	-0.1	-1000
IL12-mediated signaling events	0.0615	32	2867	87	-0.26	0.087	1000	-1000	-0.17	-1000
Visual signal transduction: Cones	0.0596	31	1204	38	-0.18	0.014	1000	-1000	-0.084	-1000
Glucocorticoid receptor regulatory network	0.0596	31	3628	114	-0.64	0.25	1000	-1000	-0.087	-1000
TCR signaling in naïve CD8+ T cells	0.0596	31	2915	93	-0.27	0.15	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0596	31	2700	85	-0.28	0.13	1000	-1000	-0.12	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0596	31	3723	120	-0.25	0.11	1000	-1000	-0.1	-1000
LPA4-mediated signaling events	0.0577	30	363	12	-0.11	0.02	1000	-1000	-0.031	-1000
Thromboxane A2 receptor signaling	0.0558	29	3143	105	-0.1	0.021	1000	-1000	-0.088	-1000
Canonical Wnt signaling pathway	0.0558	29	1506	51	-0.37	0.11	1000	-1000	-0.078	-1000
Nongenotropic Androgen signaling	0.0558	29	1513	52	-0.15	0.043	1000	-1000	-0.073	-1000
ErbB4 signaling events	0.0538	28	1948	69	-0.32	0.066	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0519	27	2752	99	-0.15	0.034	1000	-1000	-0.11	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0500	26	908	34	-0.062	0.014	1000	-1000	-0.083	-1000
IL27-mediated signaling events	0.0500	26	1352	51	-0.19	0.063	1000	-1000	-0.12	-1000
Presenilin action in Notch and Wnt signaling	0.0462	24	1510	61	-0.37	0.039	1000	-1000	-0.089	-1000
Ephrin B reverse signaling	0.0462	24	1197	48	-0.2	0.17	1000	-1000	-0.1	-1000
Signaling mediated by p38-gamma and p38-delta	0.0462	24	361	15	-0.14	0.024	1000	-1000	-0.055	-1000
Regulation of nuclear SMAD2/3 signaling	0.0442	23	3182	136	-0.36	0.36	1000	-1000	-0.096	-1000
IL1-mediated signaling events	0.0442	23	1469	62	-0.24	0.071	1000	-1000	-0.14	-1000
Syndecan-3-mediated signaling events	0.0442	23	830	35	-0.21	0.014	1000	-1000	-0.085	-1000
Integrins in angiogenesis	0.0442	23	2009	84	-0.44	0.015	1000	-1000	-0.12	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0442	23	783	33	-0.34	0.037	1000	-1000	-0.087	-1000
Wnt signaling	0.0404	21	150	7	-0.075	0.009	1000	-1000	-0.041	-1000
LPA receptor mediated events	0.0404	21	2184	102	-0.58	0.03	1000	-1000	-0.11	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0404	21	1923	88	-0.35	0.069	1000	-1000	-0.12	-1000
Arf6 signaling events	0.0365	19	1184	62	-0.16	0.04	1000	-1000	-0.077	-1000
Signaling events mediated by PTP1B	0.0365	19	1474	76	-0.14	0.028	1000	-1000	-0.1	-1000
Reelin signaling pathway	0.0365	19	1105	56	-0.24	0.014	1000	-1000	-0.099	-1000
ErbB2/ErbB3 signaling events	0.0346	18	1186	65	-0.32	0.026	1000	-1000	-0.089	-1000
Ephrin A reverse signaling	0.0346	18	131	7	-0.024	0	1000	-1000	-0.04	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0327	17	949	54	-0.31	0.028	1000	-1000	-0.12	-1000
IFN-gamma pathway	0.0327	17	1187	68	-0.2	0.038	1000	-1000	-0.12	-1000
EGFR-dependent Endothelin signaling events	0.0327	17	374	21	-0.1	0.014	1000	-1000	-0.082	-1000
Regulation of Androgen receptor activity	0.0327	17	1255	70	-0.51	0.033	1000	-1000	-0.082	-1000
PDGFR-alpha signaling pathway	0.0308	16	720	44	-0.13	0.031	1000	-1000	-0.073	-1000
Signaling mediated by p38-alpha and p38-beta	0.0308	16	747	44	-0.17	0.014	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class III	0.0288	15	635	40	-0.19	0.078	1000	-1000	-0.054	-1000
TRAIL signaling pathway	0.0288	15	746	48	-0.081	0.016	1000	-1000	-0.087	-1000
Regulation of Telomerase	0.0288	15	1576	102	-0.16	0.044	1000	-1000	-0.13	-1000
Noncanonical Wnt signaling pathway	0.0269	14	382	26	-0.081	0.014	1000	-1000	-0.097	-1000
Fc-epsilon receptor I signaling in mast cells	0.0269	14	1372	97	-0.2	0.035	1000	-1000	-0.12	-1000
S1P1 pathway	0.0269	14	510	36	-0.12	0.014	1000	-1000	-0.063	-1000
Plasma membrane estrogen receptor signaling	0.0269	14	1288	86	-0.29	0.033	1000	-1000	-0.099	-1000
VEGFR1 specific signals	0.0269	14	814	56	-0.13	0.039	1000	-1000	-0.097	-1000
EPO signaling pathway	0.0250	13	754	55	-0.075	0.027	1000	-1000	-0.12	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0250	13	498	37	-0.081	0.014	1000	-1000	-0.069	-1000
Retinoic acid receptors-mediated signaling	0.0250	13	758	58	-0.17	0.028	1000	-1000	-0.1	-1000
Signaling events mediated by PRL	0.0250	13	444	34	-0.1	0.033	1000	-1000	-0.069	-1000
Cellular roles of Anthrax toxin	0.0231	12	506	39	-0.046	0.019	1000	-1000	-0.042	-1000
Nectin adhesion pathway	0.0231	12	780	63	-0.12	0.039	1000	-1000	-0.091	-1000
IL6-mediated signaling events	0.0231	12	947	75	-0.11	0.063	1000	-1000	-0.11	-1000
IGF1 pathway	0.0231	12	690	57	-0.087	0.021	1000	-1000	-0.11	-1000
FAS signaling pathway (CD95)	0.0212	11	560	47	-0.089	0.014	1000	-1000	-0.061	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0212	11	876	74	-0.3	0.081	1000	-1000	-0.1	-1000
FOXM1 transcription factor network	0.0212	11	580	51	-0.35	0.16	1000	-1000	-0.22	-1000
IL2 signaling events mediated by PI3K	0.0192	10	614	58	-0.17	0.061	1000	-1000	-0.1	-1000
Rapid glucocorticoid signaling	0.0192	10	205	20	-0.061	0.014	1000	-1000	-0.047	-1000
Ras signaling in the CD4+ TCR pathway	0.0192	10	183	17	-0.025	0.028	1000	-1000	-0.053	-1000
Aurora B signaling	0.0192	10	707	67	-0.32	0.031	1000	-1000	-0.091	-1000
JNK signaling in the CD4+ TCR pathway	0.0173	9	167	17	-0.036	0.037	1000	-1000	-0.076	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0173	9	513	52	-0.21	0.033	1000	-1000	-0.08	-1000
S1P3 pathway	0.0173	9	395	42	-0.12	0.037	1000	-1000	-0.066	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0154	8	227	28	-0.072	0.018	1000	-1000	-0.065	-1000
Circadian rhythm pathway	0.0154	8	189	22	-0.13	0.045	1000	-1000	-0.087	-1000
Ceramide signaling pathway	0.0154	8	629	76	-0.1	0.034	1000	-1000	-0.081	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0154	8	401	45	-0.081	0.037	1000	-1000	-0.11	-1000
p38 MAPK signaling pathway	0.0154	8	369	44	-0.16	0.018	1000	-1000	-0.091	-1000
a4b1 and a4b7 Integrin signaling	0.0135	7	39	5	-0.015	0.011	1000	-1000	-0.043	-1000
Arf6 downstream pathway	0.0135	7	333	43	-0.039	0.022	1000	-1000	-0.045	-1000
Paxillin-dependent events mediated by a4b1	0.0135	7	253	36	-0.063	0.024	1000	-1000	-0.081	-1000
Class IB PI3K non-lipid kinase events	0.0135	7	21	3	-0.004	0.004	1000	-1000	-0.03	-1000
BARD1 signaling events	0.0115	6	368	57	-0.025	0.055	1000	-1000	-0.085	-1000
Aurora A signaling	0.0115	6	390	60	-0.074	0.031	1000	-1000	-0.073	-1000
HIF-2-alpha transcription factor network	0.0115	6	300	43	-0.25	0.032	1000	-1000	-0.14	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0115	6	849	125	-0.11	0.094	1000	-1000	-0.11	-1000
IL2 signaling events mediated by STAT5	0.0115	6	149	22	-0.036	0.051	1000	-1000	-0.068	-1000
Insulin Pathway	0.0115	6	511	74	-0.2	0.038	1000	-1000	-0.12	-1000
S1P4 pathway	0.0115	6	156	25	-0.032	0.024	1000	-1000	-0.067	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0096	5	446	85	-0.07	0.058	1000	-1000	-0.084	-1000
Regulation of p38-alpha and p38-beta	0.0096	5	270	54	-0.1	0.038	1000	-1000	-0.087	-1000
Hedgehog signaling events mediated by Gli proteins	0.0077	4	295	65	-0.094	0.062	1000	-1000	-0.086	-1000
Aurora C signaling	0.0077	4	32	7	-0.015	0.003	1000	-1000	-0.059	-1000
Arf6 trafficking events	0.0077	4	297	71	-0.25	0.046	1000	-1000	-0.089	-1000
PLK1 signaling events	0.0058	3	320	85	-0.019	0.035	1000	-1000	-0.061	-1000
ceramide signaling pathway	0.0058	3	194	49	-0.025	0.046	1000	-1000	-0.074	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0058	3	287	83	-0.083	0.065	1000	-1000	-0.096	-1000
TCGA08_rtk_signaling	0.0058	3	84	26	-0.031	0.047	1000	-1000	-0.03	-1000
Class I PI3K signaling events	0.0058	3	275	73	-0.1	0.04	1000	-1000	-0.09	-1000
E-cadherin signaling in keratinocytes	0.0058	3	143	43	-0.017	0.047	1000	-1000	-0.077	-1000
E-cadherin signaling events	0.0058	3	18	5	-0.006	0.012	1000	-1000	-0.051	-1000
Canonical NF-kappaB pathway	0.0038	2	91	39	-0.028	0.085	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class II	0.0038	2	157	75	-0.031	0.033	1000	-1000	-0.071	-1000
S1P5 pathway	0.0038	2	44	17	-0.014	0.024	1000	-1000	-0.066	-1000
E-cadherin signaling in the nascent adherens junction	0.0038	2	176	76	-0.017	0.058	1000	-1000	-0.1	-1000
Alternative NF-kappaB pathway	0.0038	2	30	13	-0.007	0.014	1000	-1000	-0.086	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0019	1	40	23	-0.015	0.049	1000	-1000	-0.082	-1000
PLK2 and PLK4 events	0.0019	1	4	3	0.011	0.023	1000	-1000	-0.024	-1000
Insulin-mediated glucose transport	0.0019	1	32	32	-0.078	0.048	1000	-1000	-0.082	-1000
Signaling events mediated by HDAC Class I	0.0019	1	156	104	-0.13	0.061	1000	-1000	-0.086	-1000
FoxO family signaling	0.0019	1	101	64	-0.025	0.16	1000	-1000	-0.1	-1000
Atypical NF-kappaB pathway	0.0019	1	37	31	-0.005	0.048	1000	-1000	-0.058	-1000
mTOR signaling pathway	0.0000	0	42	53	-0.003	0.034	1000	-1000	-0.08	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	19	68	-0.12	0.062	1000	-1000	-0.089	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.071	-1000
Arf1 pathway	0.0000	0	12	54	-0.004	0.036	1000	-1000	-0.045	-1000
Total	NA	3232	183938	7203	-28	7	131000	-131000	-12	-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	-0.11	0.23	-10000	0	-0.54	111	111
CDKN2C	0.01	0.15	-10000	0	-0.74	19	19
CDKN2A	-0.34	0.39	-10000	0	-0.76	238	238
CCND2	0.13	0.13	0.23	300	-0.15	1	301
RB1	-0.14	0.14	-10000	0	-0.24	300	300
CDK4	0.15	0.15	0.26	305	-10000	0	305
CDK6	0.15	0.14	0.25	299	-10000	0	299
G1/S progression	0.14	0.15	0.24	300	-10000	0	300

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.009	0.062	-9999	-0.81	3	3
CCL5	-0.11	0.29	-9999	-0.8	77	77
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.48	0.2	-9999	-0.58	374	374
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.45	0.19	-9999	-0.55	374	374
Syndecan-1/Syntenin	-0.45	0.19	-9999	-0.55	374	374
MAPK3	-0.4	0.17	-9999	-0.61	145	145
HGF/MET	-0.027	0.11	-9999	-0.49	28	28
TGFB1/TGF beta receptor Type II	0.009	0.062	-9999	-0.81	3	3
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.44	0.19	-9999	-0.54	374	374
Syndecan-1/RANTES	-0.51	0.25	-9999	-0.62	390	390
Syndecan-1/CD147	-0.43	0.18	-9999	-0.53	342	342
Syndecan-1/Syntenin/PIP2	-0.44	0.18	-9999	-0.53	374	374
LAMA5	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.42	0.18	-9999	-0.52	374	374
MMP7	-0.27	0.39	-9999	-0.8	183	183
HGF	-0.015	0.14	-9999	-0.65	22	22
Syndecan-1/CASK	-0.46	0.19	-9999	-0.56	374	374
Syndecan-1/HGF/MET	-0.44	0.19	-9999	-0.55	357	357
regulation of cell adhesion	-0.38	0.17	-9999	-0.58	145	145
HPSE	0.009	0.052	-9999	-0.58	4	4
positive regulation of cell migration	-0.48	0.2	-9999	-0.58	374	374
SDC1	-0.48	0.2	-9999	-0.58	374	374
Syndecan-1/Collagen	-0.48	0.2	-9999	-0.58	374	374
PPIB	0.014	0	-9999	-10000	0	0
MET	0.005	0.08	-9999	-0.73	6	6
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.58	0.37	-9999	-0.81	374	374
MAPK1	-0.4	0.17	-9999	-0.61	145	145
homophilic cell adhesion	-0.47	0.19	-9999	-0.57	374	374
MMP1	-0.71	0.26	-9999	-0.81	460	460

×

IL4-mediated signaling events

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
BCL2L1	-1	0.5	-10000	0	-1.4	334	334
STAT6 (cleaved dimer)	-1.1	0.52	-10000	0	-1.4	370	370
IGHG1	-0.33	0.13	-10000	0	-0.47	121	121
IGHG3	-1	0.48	-10000	0	-1.3	358	358
AKT1	-0.4	0.18	-10000	0	-0.75	39	39
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.29	0.16	-10000	0	-0.73	28	28
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.41	0.18	-10000	0	-0.79	26	26
THY1	-1.1	0.55	-10000	0	-1.5	341	341
MYB	-0.047	0.18	-10000	0	-0.6	51	51
HMGA1	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.51	0.23	-10000	0	-0.94	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.41	0.18	-10000	0	-0.77	25	25
SP1	0.014	0.011	-10000	0	-10000	0	0
INPP5D	0.011	0.037	-10000	0	-0.58	2	2
SOCS5	0.035	0.01	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-1.1	0.52	-10000	0	-1.4	351	351
SOCS1	-0.64	0.27	-10000	0	-0.84	255	255
SOCS3	-0.42	0.2	-10000	0	-0.81	40	40
FCER2	-0.74	0.35	-10000	0	-1	213	213
PARP14	0.009	0.062	-10000	0	-0.81	3	3
CCL17	-1.1	0.51	-10000	0	-1.4	338	338
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.33	0.15	-10000	0	-0.74	19	19
T cell proliferation	-1.1	0.53	-10000	0	-1.4	339	339
IL4R/JAK1	-1	0.5	-10000	0	-1.4	336	336
EGR2	-1.1	0.51	-10000	0	-1.4	328	328
JAK2	-0.032	0.032	-10000	0	-0.62	1	1
JAK3	-0.014	0.17	-10000	0	-0.81	22	22
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
JAK1	0.001	0.005	-10000	0	-10000	0	0
COL1A2	-0.48	0.35	-10000	0	-0.93	192	192
CCL26	-1.1	0.52	-10000	0	-1.4	328	328
IL4R	-1.1	0.55	-10000	0	-1.5	336	336
PTPN6	0.035	0.007	-10000	0	-10000	0	0
IL13RA2	-1.1	0.52	-10000	0	-1.4	332	332
IL13RA1	-0.031	0.019	-10000	0	-10000	0	0
IRF4	-0.27	0.32	-10000	0	-0.93	87	87
ARG1	-0.59	0.6	-10000	0	-1.4	171	171
CBL	-0.48	0.22	-10000	0	-0.9	48	48
GTF3A	0.006	0.018	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.043	0.031	-10000	0	-0.46	1	1
IRF4/BCL6	-0.25	0.3	-10000	0	-0.87	86	86
CD40LG	-0.057	0.2	-10000	0	-0.59	65	65
MAPK14	-0.47	0.22	-10000	0	-0.9	48	48
mitosis	-0.38	0.18	-10000	0	-0.71	38	38
STAT6	-1.3	0.7	-10000	0	-1.7	351	351
SPI1	-0.021	0.075	-10000	0	-0.75	3	3
RPS6KB1	-0.36	0.17	-10000	0	-0.71	28	28
STAT6 (dimer)	-1.3	0.7	-10000	0	-1.7	351	351
STAT6 (dimer)/PARP14	-1.2	0.59	-10000	0	-1.5	349	349
mast cell activation	0.021	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.39	0.18	-10000	0	-0.81	33	33
FRAP1	-0.4	0.18	-10000	0	-0.74	40	40
LTA	-1.1	0.51	-10000	0	-1.4	339	339
FES	0.014	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	1.2	0.62	1.6	351	-10000	0	351
CCL11	-1.2	0.49	-10000	0	-1.4	377	377
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.39	0.18	-10000	0	-0.8	32	32
IL2RG	-0.005	0.14	-10000	0	-0.78	17	17
IL10	-1.1	0.5	-10000	0	-1.4	336	336
IRS1	0.01	0.045	-10000	0	-0.58	3	3
IRS2	0.011	0.037	-10000	0	-0.58	2	2
IL4	-0.2	0.074	-10000	0	-10000	0	0
IL5	-1.1	0.5	-10000	0	-1.4	326	326
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.77	0.32	-10000	0	-0.97	320	320
COL1A1	-0.66	0.37	-10000	0	-0.95	316	316
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-1.1	0.54	-10000	0	-1.5	320	320
IL2R gamma/JAK3	-0.023	0.18	-10000	0	-0.67	35	35
TFF3	-1.3	0.59	-10000	0	-1.6	378	378
ALOX15	-1.1	0.54	-10000	0	-1.5	343	343
MYBL1	-0.002	0.11	-10000	0	-0.81	10	10
T-helper 2 cell differentiation	-0.78	0.33	-10000	0	-1	330	330
SHC1	0.014	0	-10000	0	-10000	0	0
CEBPB	-0.016	0.05	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.39	0.17	-10000	0	-0.74	28	28
mol:PI-3-4-5-P3	-0.4	0.18	-10000	0	-0.74	40	40
PI3K	-0.42	0.2	-10000	0	-0.8	40	40
DOK2	0.008	0.067	-10000	0	-0.75	4	4
ETS1	0.03	0.063	-10000	0	-0.8	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.31	0.14	-10000	0	-0.69	22	22
ITGB3	-1.1	0.51	-10000	0	-1.4	332	332
PIGR	-1.4	0.61	-10000	0	-1.7	396	396
IGHE	0.05	0.044	0.27	3	-10000	0	3
MAPKKK cascade	-0.3	0.14	-10000	0	-0.68	22	22
BCL6	0.013	0.002	-10000	0	-10000	0	0
OPRM1	-1.1	0.5	-10000	0	-1.4	334	334
RETNLB	-1.1	0.51	-10000	0	-1.4	337	337
SELP	-1.1	0.55	-10000	0	-1.5	338	338
AICDA	-1	0.48	-10000	0	-1.3	338	338

×

Syndecan-4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.21	0.23	-9999	-0.46	228	228
Syndecan-4/Syndesmos	-0.38	0.26	-9999	-0.62	225	225
positive regulation of JNK cascade	-0.39	0.22	-9999	-0.58	261	261
Syndecan-4/ADAM12	-0.68	0.35	-9999	-0.91	337	337
CCL5	-0.11	0.29	-9999	-0.8	77	77
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.24	0.38	-9999	-0.81	164	164
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0.001	0.079	-9999	-0.79	5	5
ADAM12	-0.58	0.37	-9999	-0.81	375	375
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.12	0.062	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.56	0.34	-9999	-0.81	300	300
Syndecan-4/CXCL12/CXCR4	-0.4	0.26	-9999	-0.62	261	261
Syndecan-4/Laminin alpha3	-0.49	0.34	-9999	-0.76	273	273
MDK	-0.024	0.17	-9999	-0.8	24	24
Syndecan-4/FZD7	-0.39	0.26	-9999	-0.63	228	228
Syndecan-4/Midkine	-0.4	0.26	-9999	-0.64	238	238
FZD7	0.001	0.098	-9999	-0.78	8	8
Syndecan-4/FGFR1/FGF	-0.37	0.23	-9999	-0.58	236	236
THBS1	-0.012	0.14	-9999	-0.73	18	18
integrin-mediated signaling pathway	-0.44	0.3	-9999	-0.7	251	251
positive regulation of MAPKKK cascade	-0.39	0.22	-9999	-0.58	261	261
Syndecan-4/TACI	-0.42	0.28	-9999	-0.67	253	253
CXCR4	-0.015	0.15	-9999	-0.81	18	18
cell adhesion	-0.18	0.21	-9999	-0.39	229	229
Syndecan-4/Dynamin	-0.38	0.26	-9999	-0.62	225	225
Syndecan-4/TSP1	-0.39	0.27	-9999	-0.64	228	228
Syndecan-4/GIPC	-0.38	0.26	-9999	-0.62	225	225
Syndecan-4/RANTES	-0.44	0.3	-9999	-0.69	261	261
ITGB1	0.012	0.036	-9999	-0.81	1	1
LAMA1	-0.35	0.41	-9999	-0.8	231	231
LAMA3	-0.21	0.37	-9999	-0.8	144	144
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.09	0.07	-9999	-0.66	2	2
Syndecan-4/alpha-Actinin	-0.38	0.26	-9999	-0.62	225	225
TFPI	0.007	0.072	-9999	-0.72	5	5
F2	-0.084	0.25	-9999	-0.81	53	53
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.62	165	165
positive regulation of cell adhesion	-0.63	0.38	-9999	-0.87	327	327
ACTN1	0.012	0.036	-9999	-0.81	1	1
TNC	-0.14	0.32	-9999	-0.81	98	98
Syndecan-4/CXCL12	-0.41	0.25	-9999	-0.63	254	254
FGF6	0.003	0.005	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	-0.05	0.18	-9999	-0.58	56	56
TNFRSF13B	-0.072	0.25	-9999	-0.81	53	53
FGF2	-0.008	0.12	-9999	-0.63	17	17
FGFR1	0.003	0.091	-9999	-0.77	7	7
Syndecan-4/PI-4-5-P2	-0.39	0.25	-9999	-0.63	225	225
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.34	0.41	-9999	-0.8	228	228
cell migration	-0.039	0.02	-9999	-10000	0	0
PRKCD	0.026	0.011	-9999	-10000	0	0
vasculogenesis	-0.38	0.25	-9999	-0.61	228	228
SDC4	-0.41	0.27	-9999	-0.67	225	225
Syndecan-4/Tenascin C	-0.46	0.33	-9999	-0.74	251	251
Syndecan-4/PI-4-5-P2/PKC alpha	-0.091	0.048	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.38	0.26	-9999	-0.62	225	225
MMP9	-0.57	0.37	-9999	-0.8	374	374
Rac1/GTP	-0.19	0.21	-9999	-0.4	229	229
cytoskeleton organization	-0.36	0.24	-9999	-0.6	225	225
GIPC1	0.014	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.38	0.26	-9999	-0.62	228	228

×

Osteopontin-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.28	0.27	-9999	-0.56	164	164
NF kappa B1 p50/RelA/I kappa B alpha	-0.28	0.23	-9999	-0.57	150	150
alphaV/beta3 Integrin/Osteopontin/Src	-0.35	0.32	-9999	-0.63	287	287
AP1	-0.32	0.32	-9999	-0.8	97	97
ILK	-0.28	0.28	-9999	-0.57	164	164
bone resorption	-0.22	0.25	-9999	-0.74	20	20
PTK2B	0.012	0.026	-9999	-0.58	1	1
PYK2/p130Cas	-0.27	0.24	-9999	-0.52	149	149
ITGAV	0.004	0.077	-9999	-0.77	5	5
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.008	0.057	-9999	-0.42	10	10
alphaV/beta3 Integrin/Osteopontin	-0.33	0.29	-9999	-0.58	291	291
MAP3K1	-0.29	0.29	-9999	-0.53	291	291
JUN	0.013	0.002	-9999	-10000	0	0
MAPK3	-0.3	0.29	-9999	-0.62	164	164
MAPK1	-0.3	0.29	-9999	-0.62	164	164
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.27	0.28	-9999	-0.56	166	166
ITGB3	-0.019	0.15	-9999	-0.74	21	21
NFKBIA	-0.29	0.28	-9999	-0.63	152	152
FOS	-0.063	0.2	-9999	-0.58	67	67
CD44	0.012	0.026	-9999	-0.58	1	1
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.44	0.39	-9999	-0.92	163	163
NF kappa B1 p50/RelA	-0.3	0.24	-9999	-0.61	149	149
BCAR1	0.014	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.029	0.13	-9999	-0.59	25	25
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.28	0.28	-9999	-0.52	291	291
VAV3	-0.28	0.28	-9999	-0.51	291	291
MAP3K14	-0.3	0.29	-9999	-0.54	291	291
ROCK2	0.003	0.077	-9999	-0.58	9	9
SPP1	-0.44	0.41	-9999	-0.82	285	285
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.27	0.24	-9999	-0.51	184	184
MMP2	-0.28	0.31	-9999	-0.8	90	90

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.69	0.47	-9999	-1.2	148	148
HDAC7	0.014	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.47	0.32	-9999	-0.93	57	57
SMAD4	0.014	0.026	-9999	-0.57	1	1
ID2	-0.69	0.47	-9999	-1.2	150	150
AP1	-0.05	0.14	-9999	-0.41	67	67
ABCG2	-0.69	0.48	-9999	-1.3	151	151
HIF1A	-0.084	0.061	-9999	-0.72	1	1
TFF3	-0.82	0.53	-9999	-1.3	216	216
GATA2	0.011	0.058	-9999	-0.74	3	3
AKT1	-0.085	0.063	-9999	-10000	0	0
response to hypoxia	-0.11	0.065	-9999	-10000	0	0
MCL1	-0.69	0.47	-9999	-1.2	148	148
NDRG1	-0.69	0.48	-9999	-1.3	147	147
SERPINE1	-0.91	0.55	-9999	-1.4	265	265
FECH	-0.69	0.47	-9999	-1.2	148	148
FURIN	-0.69	0.47	-9999	-1.2	152	152
NCOA2	-0.035	0.16	-9999	-0.58	42	42
EP300	-0.09	0.092	-9999	-0.42	3	3
HMOX1	-0.69	0.47	-9999	-1.2	150	150
BHLHE40	-0.69	0.47	-9999	-1.2	148	148
BHLHE41	-0.7	0.48	-9999	-1.3	151	151
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.068	0.057	-9999	-10000	0	0
ENG	-0.045	0.072	-9999	-10000	0	0
JUN	0.014	0.001	-9999	-10000	0	0
RORA	-0.69	0.48	-9999	-1.3	148	148
ABCB1	-0.2	0.31	-9999	-1.4	30	30
TFRC	-0.7	0.48	-9999	-1.3	155	155
CXCR4	-0.7	0.48	-9999	-1.3	153	153
TF	-0.86	0.53	-9999	-1.3	235	235
CITED2	-0.69	0.47	-9999	-1.2	148	148
HIF1A/ARNT	-0.79	0.59	-9999	-1.4	217	217
LDHA	-0.069	0.044	-9999	-10000	0	0
ETS1	-0.69	0.47	-9999	-1.3	148	148
PGK1	-0.69	0.47	-9999	-1.2	148	148
NOS2	-0.75	0.49	-9999	-1.3	172	172
ITGB2	-0.7	0.48	-9999	-1.3	153	153
ALDOA	-0.69	0.47	-9999	-1.2	148	148
Cbp/p300/CITED2	-0.67	0.48	-9999	-1.3	133	133
FOS	-0.062	0.2	-9999	-0.58	67	67
HK2	-0.69	0.47	-9999	-1.2	148	148
SP1	0.022	0.005	-9999	-10000	0	0
GCK	-0.18	0.22	-9999	-0.8	40	40
HK1	-0.69	0.47	-9999	-1.2	149	149
NPM1	-0.69	0.47	-9999	-1.2	149	149
EGLN1	-0.69	0.47	-9999	-1.2	148	148
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.69	0.47	-9999	-1.2	149	149
SMAD3	0.014	0.026	-9999	-0.57	1	1
EDN1	-0.09	0.17	-9999	-1.4	5	5
IGFBP1	-0.7	0.48	-9999	-1.3	154	154
VEGFA	-0.4	0.3	-9999	-1	20	20
HIF1A/JAB1	-0.043	0.035	-9999	-0.54	1	1
CP	-0.81	0.54	-9999	-1.3	207	207
CXCL12	-0.72	0.49	-9999	-1.3	154	154
COPS5	0.013	0.005	-9999	-10000	0	0
SMAD3/SMAD4	-0.002	0.025	-9999	-0.41	2	2
BNIP3	-0.69	0.47	-9999	-1.2	152	152
EGLN3	-0.71	0.49	-9999	-1.3	152	152
CA9	-1	0.49	-9999	-1.3	325	325
TERT	-0.77	0.52	-9999	-1.3	187	187
ENO1	-0.69	0.47	-9999	-1.2	148	148
PFKL	-0.69	0.47	-9999	-1.2	148	148
NCOA1	0.013	0.002	-9999	-10000	0	0
ADM	-0.69	0.48	-9999	-1.2	152	152
ARNT	-0.082	0.053	-9999	-10000	0	0
HNF4A	-0.071	0.24	-9999	-0.81	51	51
ADFP	-0.7	0.47	-9999	-1.2	176	176
SLC2A1	-0.4	0.3	-9999	-1	24	24
LEP	-0.74	0.51	-9999	-1.3	173	173
HIF1A/ARNT/Cbp/p300	-0.49	0.34	-9999	-0.92	83	83
EPO	-0.4	0.32	-9999	-0.98	72	72
CREBBP	-0.089	0.09	-9999	-0.37	2	2
HIF1A/ARNT/Cbp/p300/HDAC7	-0.46	0.33	-9999	-1	35	35
PFKFB3	-0.69	0.47	-9999	-1.2	149	149
NT5E	-0.75	0.52	-9999	-1.3	178	178

×

Glypican 2 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.024	0.17	-9999	-0.8	24	24
GPC2	-0.15	0.33	-9999	-0.81	104	104
GPC2/Midkine	-0.15	0.29	-9999	-0.68	114	114
neuron projection morphogenesis	-0.15	0.29	-9999	-0.68	114	114

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.12	0.26	-9999	-0.63	94	94
alphaM/beta2 Integrin/GPIbA	-0.067	0.2	-9999	-0.69	45	45
alphaM/beta2 Integrin/proMMP-9	-0.43	0.3	-9999	-0.59	377	377
PLAUR	-0.032	0.19	-9999	-0.81	29	29
HMGB1	0.011	0.016	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.053	0.18	-9999	-0.67	38	38
AGER	-0.001	0.095	-9999	-0.8	7	7
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	0.014	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.072	0.19	-9999	-0.63	41	41
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.58	0.37	-9999	-0.81	374	374
CYR61	0.005	0.084	-9999	-0.77	6	6
TLN1	0.01	0.051	-9999	-0.81	2	2
Rap1/GTP	-0.16	0.15	-9999	-0.48	53	53
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.084	0.22	-9999	-0.58	86	86
MYH2	-0.36	0.25	-9999	-0.57	254	254
MST1R	0.004	0.073	-9999	-0.58	8	8
leukocyte activation during inflammatory response	-0.069	0.19	-9999	-0.55	62	62
APOB	-0.017	0.15	-9999	-0.8	18	18
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.091	0.27	-9999	-0.81	66	66
JAM3	0.012	0.036	-9999	-0.81	1	1
GP1BA	-0.014	0.14	-9999	-0.74	18	18
alphaM/beta2 Integrin/CTGF	-0.058	0.19	-9999	-0.66	41	41
alphaM/beta2 Integrin	-0.18	0.19	-9999	-0.43	155	155
JAM3 homodimer	0.012	0.036	-9999	-0.81	1	1
ICAM2	0.011	0.037	-9999	-0.58	2	2
ICAM1	-0.026	0.18	-9999	-0.81	25	25
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.18	0.19	-9999	-0.42	155	155
cell adhesion	-0.067	0.2	-9999	-0.69	45	45
NFKB1	-0.03	0.22	-9999	-0.83	21	21
THY1	-0.22	0.37	-9999	-0.81	147	147
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.03	0.12	-9999	-0.54	29	29
alphaM/beta2 Integrin/LRP/tPA	-0.063	0.19	-9999	-0.59	52	52
IL6	-0.06	0.29	-9999	-0.78	64	64
ITGB2	-0.013	0.14	-9999	-0.79	15	15
elevation of cytosolic calcium ion concentration	-0.28	0.32	-9999	-0.57	255	255
alphaM/beta2 Integrin/JAM2/JAM3	-0.054	0.17	-9999	-0.63	37	37
JAM2	0	0.089	-9999	-0.58	12	12
alphaM/beta2 Integrin/ICAM1	-0.073	0.21	-9999	-0.61	56	56
alphaM/beta2 Integrin/uPA/Plg	-0.27	0.29	-9999	-0.54	257	257
RhoA/GTP	-0.22	0.22	-9999	-0.52	144	144
positive regulation of phagocytosis	-0.14	0.17	-9999	-0.57	46	46
Ron/MSP	-0.013	0.078	-9999	-0.47	14	14
alphaM/beta2 Integrin/uPAR/uPA	-0.28	0.33	-9999	-0.58	255	255
alphaM/beta2 Integrin/uPAR	-0.08	0.23	-9999	-0.67	59	59
PLAU	-0.35	0.41	-9999	-0.81	230	230
PLAT	-0.014	0.15	-9999	-0.8	18	18
actin filament polymerization	-0.34	0.23	-9999	-0.54	254	254
MST1	0.005	0.08	-9999	-0.73	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.07	0.19	-9999	-0.56	62	62
TNF	-0.035	0.25	-9999	-0.76	38	38
RAP1B	0.012	0.036	-9999	-0.81	1	1
alphaM/beta2 Integrin/uPA	-0.28	0.31	-9999	-0.58	252	252
fibrinolysis	-0.26	0.29	-9999	-0.53	257	257
HCK	0.006	0.076	-9999	-0.76	5	5
dendritic cell antigen processing and presentation	-0.18	0.19	-9999	-0.42	155	155
VTN	-0.039	0.2	-9999	-0.81	33	33
alphaM/beta2 Integrin/CYR61	-0.057	0.19	-9999	-0.67	41	41
LPA	-0.009	0.12	-9999	-0.81	11	11
LRP1	0.012	0.026	-9999	-0.58	1	1
cell migration	-0.45	0.35	-9999	-0.61	380	380
FN1	-0.35	0.41	-9999	-0.81	228	228
alphaM/beta2 Integrin/Thy1	-0.2	0.31	-9999	-0.62	164	164
MPO	-0.022	0.14	-9999	-0.59	30	30
KNG1	-0.023	0.15	-9999	-0.81	18	18
RAP1/GDP	-0.001	0.024	-9999	-0.54	1	1
ROCK1	-0.2	0.21	-9999	-0.49	136	136
ELA2	0	0	-9999	-10000	0	0
PLG	-0.006	0.079	-9999	-0.81	5	5
CTGF	0.001	0.088	-9999	-0.62	10	10
alphaM/beta2 Integrin/Hck	-0.056	0.18	-9999	-0.66	40	40
ITGAM	-0.04	0.2	-9999	-0.8	32	32
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.097	0.2	-9999	-0.64	36	36
HP	-0.21	0.29	-9999	-0.58	190	190
leukocyte adhesion	-0.17	0.25	-9999	-0.76	45	45
SELP	-0.084	0.22	-9999	-0.58	86	86

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.56	0.44	-10000	0	-1.2	111	111
IL23A	-0.56	0.43	-10000	0	-1.2	108	108
NF kappa B1 p50/RelA/I kappa B alpha	-0.55	0.42	-10000	0	-1.1	131	131
positive regulation of T cell mediated cytotoxicity	-0.61	0.49	-10000	0	-1.3	133	133
ITGA3	-0.55	0.42	-10000	0	-1.2	108	108
IL17F	-0.37	0.27	-10000	0	-0.74	86	86
IL12B	-0.074	0.24	-10000	0	-0.85	44	44
STAT1 (dimer)	-0.6	0.48	-10000	0	-1.2	145	145
CD4	-0.53	0.41	-10000	0	-1.1	103	103
IL23	-0.56	0.43	-10000	0	-1.2	113	113
IL23R	-0.083	0.091	-10000	0	-0.69	6	6
IL1B	-0.57	0.45	-10000	0	-1.2	113	113
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.73	0.43	-10000	0	-1.2	196	196
TYK2	-0.005	0.039	-10000	0	-0.85	1	1
STAT4	-0.008	0.13	-10000	0	-0.79	14	14
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.013	0.14	-10000	0	-0.73	18	18
IL12RB1	-0.066	0.22	-10000	0	-0.83	39	39
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.057	0.17	-10000	0	-0.65	40	40
IL23R/JAK2	-0.1	0.097	-10000	0	-0.74	4	4
positive regulation of chronic inflammatory response	-0.61	0.49	-10000	0	-1.3	133	133
natural killer cell activation	0.008	0.008	0.059	6	-10000	0	6
JAK2	0.002	0.028	-10000	0	-0.57	1	1
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
NFKB1	0.01	0.003	-10000	0	-10000	0	0
RELA	0.01	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.53	0.41	-10000	0	-1.1	113	113
ALOX12B	-0.63	0.48	-10000	0	-1.2	160	160
CXCL1	-0.57	0.44	-10000	0	-1.2	118	118
T cell proliferation	-0.61	0.49	-10000	0	-1.3	133	133
NFKBIA	0.008	0.036	-10000	0	-0.81	1	1
IL17A	-0.28	0.22	-10000	0	-0.62	34	34
PI3K	-0.56	0.43	-10000	0	-1.1	133	133
IFNG	-0.031	0.045	0.13	5	-0.11	98	103
STAT3 (dimer)	-0.53	0.4	-10000	0	-1.1	131	131
IL18R1	0.01	0.044	-10000	0	-0.69	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.32	0.25	-10000	0	-0.81	45	45
IL18/IL18R	-0.007	0.12	-10000	0	-0.57	14	14
macrophage activation	-0.028	0.015	-10000	0	-0.045	55	55
TNF	-0.57	0.44	-10000	0	-1.2	107	107
STAT3/STAT4	-0.57	0.43	-10000	0	-1.1	139	139
STAT4 (dimer)	-0.59	0.47	-10000	0	-1.2	133	133
IL18	-0.009	0.11	-10000	0	-0.57	19	19
IL19	-0.67	0.53	-10000	0	-1.3	180	180
STAT5A (dimer)	-0.58	0.46	-10000	0	-1.2	130	130
STAT1	-0.033	0.19	-10000	0	-0.79	30	30
SOCS3	0.012	0.026	-10000	0	-0.58	1	1
CXCL9	-0.68	0.47	-10000	0	-1.2	199	199
MPO	-0.56	0.44	-10000	0	-1.2	121	121
positive regulation of humoral immune response	-0.61	0.49	-10000	0	-1.3	133	133
IL23/IL23R/JAK2/TYK2	-0.64	0.53	-10000	0	-1.4	131	131
IL6	-0.58	0.47	-10000	0	-1.2	124	124
STAT5A	0.014	0	-10000	0	-10000	0	0
IL2	0.007	0.037	-10000	0	-0.8	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.008	0.059	6	-10000	0	6
CD3E	-0.54	0.42	-10000	0	-1.2	103	103
keratinocyte proliferation	-0.61	0.49	-10000	0	-1.3	133	133
NOS2	-0.58	0.44	-10000	0	-1.2	128	128

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.24	0.31	-9999	-0.58	232	232
EPHB2	-0.2	0.36	-9999	-0.81	138	138
Syndecan-2/TACI	-0.061	0.2	-9999	-0.54	77	77
LAMA1	-0.35	0.41	-9999	-0.8	231	231
Syndecan-2/alpha2 ITGB1	-0.15	0.22	-9999	-0.47	162	162
HRAS	0.012	0.036	-9999	-0.81	1	1
Syndecan-2/CASK	-0.026	0.12	-9999	-0.54	25	25
ITGA5	-0.24	0.38	-9999	-0.81	164	164
BAX	0.014	0.12	-9999	-0.76	2	2
EPB41	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.023	0.1	-9999	-0.49	25	25
LAMA3	-0.21	0.37	-9999	-0.8	144	144
EZR	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.01	0.051	-9999	-0.65	3	3
Syndecan-2/MMP2	-0.07	0.24	-9999	-0.62	77	77
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.004	0.041	-9999	-0.47	4	4
dendrite morphogenesis	-0.15	0.27	-9999	-0.56	154	154
Syndecan-2/GM-CSF	-0.3	0.3	-9999	-0.56	285	285
determination of left/right symmetry	-0.009	0.14	-9999	-0.62	25	25
Syndecan-2/PKC delta	-0.001	0.12	-9999	-0.53	25	25
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	-0.26	0.28	-9999	-0.51	285	285
MAPK1	-0.26	0.28	-9999	-0.51	285	285
Syndecan-2/RACK1	-0.023	0.1	-9999	-0.46	26	26
NF1	0.014	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.009	0.14	-9999	-0.62	25	25
ITGA2	0.01	0.045	-9999	-0.58	3	3
MAPK8	0.005	0.13	-9999	-0.55	25	25
Syndecan-2/alpha2/beta1 Integrin	-0.22	0.26	-9999	-0.49	234	234
Syndecan-2/Kininogen	-0.035	0.16	-9999	-0.56	41	41
ITGB1	0.012	0.036	-9999	-0.81	1	1
SRC	0.016	0.1	-9999	-0.43	26	26
Syndecan-2/CASK/Protein 4.1	-0.024	0.1	-9999	-0.49	25	25
extracellular matrix organization	-0.004	0.13	-9999	-0.55	27	27
actin cytoskeleton reorganization	-0.24	0.31	-9999	-0.57	232	232
Syndecan-2/Caveolin-2/Ras	-0.026	0.11	-9999	-0.49	27	27
Syndecan-2/Laminin alpha3	-0.15	0.27	-9999	-0.55	162	162
Syndecan-2/RasGAP	-0.023	0.098	-9999	-0.44	26	26
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.62	165	165
PRKCD	0.014	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.15	0.28	-9999	-0.56	154	154
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.022	0.1	-9999	-0.42	26	26
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.072	0.25	-9999	-0.81	53	53
RASA1	0.011	0.037	-9999	-0.58	2	2
alpha2/beta1 Integrin	-0.004	0.041	-9999	-0.47	4	4
Syndecan-2/Synbindin	-0.001	0.12	-9999	-0.53	25	25
TGFB1	0.009	0.062	-9999	-0.81	3	3
CASP3	0.01	0.11	-9999	-0.48	25	25
FN1	-0.35	0.41	-9999	-0.81	228	228
Syndecan-2/IL8	-0.11	0.26	-9999	-0.56	125	125
SDC2	-0.009	0.14	-9999	-0.62	25	25
KNG1	-0.023	0.15	-9999	-0.81	18	18
Syndecan-2/Neurofibromin	-0.001	0.12	-9999	-0.53	25	25
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	-0.42	0.41	-9999	-0.81	277	277
Syndecan-2/TGFB1	-0.004	0.13	-9999	-0.55	27	27
Syndecan-2/Syntenin/PI-4-5-P2	-0.024	0.1	-9999	-0.49	25	25
Syndecan-2/Ezrin	-0.023	0.1	-9999	-0.48	25	25
PRKACA	0.01	0.11	-9999	-0.48	25	25
angiogenesis	-0.11	0.25	-9999	-0.55	125	125
MMP2	-0.091	0.27	-9999	-0.81	66	66
IL8	-0.15	0.33	-9999	-0.8	107	107
calcineurin-NFAT signaling pathway	-0.061	0.2	-9999	-0.54	77	77

×

TCGA08_p53

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
CDKN2A	-0.26	0.3	-10000	0	-0.59	238	238
TP53	-0.077	0.087	-10000	0	-0.46	4	4
Senescence	-0.077	0.087	-10000	0	-0.46	4	4
Apoptosis	-0.077	0.087	-10000	0	-0.46	4	4
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.13	0.15	0.29	238	-10000	0	238
MDM4	0.014	0	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.16	0.3	-10000	0	-0.69	62	62
PTK2B	0.012	0.026	-10000	0	-0.58	1	1
mol:Ca2+	-0.041	0.2	-10000	0	-0.68	23	23
EDN1	-0.086	0.21	-10000	0	-0.41	46	46
EDN3	-0.23	0.29	-10000	0	-0.58	211	211
EDN2	-0.088	0.24	-10000	0	-0.66	79	79
HRAS/GDP	-0.044	0.17	-10000	0	-0.54	14	14
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.047	0.15	-10000	0	-0.4	27	27
ADCY4	-0.18	0.24	-10000	0	-0.59	82	82
ADCY5	-0.26	0.25	-10000	0	-0.59	134	134
ADCY6	-0.18	0.25	-10000	0	-0.58	92	92
ADCY7	-0.18	0.24	-10000	0	-0.58	87	87
ADCY1	-0.2	0.27	-10000	0	-0.62	98	98
ADCY2	-0.28	0.26	-10000	0	-0.59	160	160
ADCY3	-0.18	0.24	-10000	0	-0.59	82	82
ADCY8	-0.2	0.25	-10000	0	-0.6	96	96
ADCY9	-0.18	0.24	-10000	0	-0.58	88	88
arachidonic acid secretion	-0.07	0.21	-10000	0	-0.52	55	55
ETB receptor/Endothelin-1/Gq/GTP	-0.049	0.14	-10000	0	-0.44	25	25
GNAO1	0.008	0.067	-10000	0	-0.75	4	4
HRAS	0.011	0.036	-10000	0	-0.81	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.076	0.35	0.34	148	-0.66	62	210
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.34	0.32	126	-0.61	91	217
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	-0.39	0.49	-10000	0	-0.83	271	271
EDNRB	-0.014	0.062	-10000	0	-0.57	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.21	0.38	-10000	0	-0.9	78	78
CYSLTR1	-0.21	0.36	-10000	0	-0.77	97	97
SLC9A1	-0.058	0.16	-10000	0	-0.33	48	48
mol:GDP	-0.053	0.18	-10000	0	-0.53	19	19
SLC9A3	-0.17	0.32	-10000	0	-0.7	110	110
RAF1	-0.073	0.19	-10000	0	-0.5	43	43
JUN	-0.028	0.17	-10000	0	-0.63	5	5
JAK2	-0.16	0.3	-10000	0	-0.67	66	66
mol:IP3	-0.065	0.16	-10000	0	-0.5	24	24
ETA receptor/Endothelin-1	-0.12	0.42	0.4	153	-0.76	67	220
PLCB1	0.008	0.051	-10000	0	-0.65	3	3
PLCB2	0.007	0.068	-10000	0	-0.76	4	4
ETA receptor/Endothelin-3	-0.22	0.25	-10000	0	-0.48	215	215
FOS	-0.12	0.34	-10000	0	-0.94	68	68
Gai/GDP	0.016	0.072	-10000	0	-0.59	2	2
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.17	0.28	-10000	0	-0.69	67	67
BCAR1	0.014	0	-10000	0	-10000	0	0
PRKCB1	-0.063	0.16	-10000	0	-0.47	26	26
GNAQ	0.014	0.006	-10000	0	-10000	0	0
GNAZ	-0.014	0.14	-10000	0	-0.74	19	19
GNAL	-0.061	0.2	-10000	0	-0.58	66	66
Gs family/GDP	-0.12	0.15	-10000	0	-0.51	36	36
ETA receptor/Endothelin-1/Gq/GTP	-0.067	0.18	-10000	0	-0.45	38	38
MAPK14	-0.025	0.12	-10000	0	-0.71	4	4
TRPC6	-0.043	0.2	-10000	0	-0.71	23	23
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.026	-10000	0	-0.58	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.035	0.12	-10000	0	-0.5	10	10
ETB receptor/Endothelin-2	-0.076	0.19	-10000	0	-0.49	83	83
ETB receptor/Endothelin-3	-0.18	0.21	-10000	0	-0.43	214	214
ETB receptor/Endothelin-1	-0.067	0.18	-10000	0	-0.56	8	8
MAPK3	-0.1	0.29	-10000	0	-0.78	70	70
MAPK1	-0.1	0.29	-10000	0	-0.78	70	70
Rac1/GDP	-0.043	0.17	-10000	0	-0.53	14	14
cAMP biosynthetic process	-0.23	0.22	-10000	0	-0.56	108	108
MAPK8	-0.045	0.19	-10000	0	-0.6	21	21
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.011	0.096	-10000	0	-0.39	9	9
p130Cas/CRK/Src/PYK2	-0.049	0.18	-10000	0	-0.57	17	17
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.046	0.17	-10000	0	-0.53	16	16
COL1A2	-0.28	0.46	-10000	0	-0.84	194	194
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.12	0.23	-10000	0	-0.56	82	82
mol:DAG	-0.065	0.16	-10000	0	-0.5	24	24
MAP2K2	-0.083	0.23	-10000	0	-0.62	52	52
MAP2K1	-0.083	0.23	-10000	0	-0.62	52	52
EDNRA	-0.079	0.2	-10000	0	-0.41	46	46
positive regulation of muscle contraction	-0.13	0.26	-10000	0	-0.65	50	50
Gq family/GDP	-0.079	0.15	-10000	0	-0.52	25	25
HRAS/GTP	-0.069	0.17	-10000	0	-0.48	33	33
PRKCH	-0.056	0.16	-10000	0	-0.48	23	23
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.057	0.16	-10000	0	-0.48	24	24
PRKCB	-0.062	0.17	-10000	0	-0.51	30	30
PRKCE	-0.056	0.16	-10000	0	-0.48	23	23
PRKCD	-0.056	0.16	-10000	0	-0.48	24	24
PRKCG	-0.11	0.21	-10000	0	-0.53	66	66
regulation of vascular smooth muscle contraction	-0.14	0.39	-10000	0	-1.1	69	69
PRKCQ	-0.063	0.17	-10000	0	-0.49	30	30
PLA2G4A	-0.077	0.22	-10000	0	-0.56	55	55
GNA14	-0.071	0.21	-10000	0	-0.58	75	75
GNA15	0.011	0.037	-10000	0	-0.58	2	2
GNA12	0.007	0.072	-10000	0	-0.81	4	4
GNA11	0.009	0.052	-10000	0	-0.58	4	4
Rac1/GTP	-0.071	0.35	0.34	152	-0.64	62	214
MMP1	-0.56	0.24	-10000	0	-0.65	460	460

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.016	0.08	-9999	-0.42	20	20
Necdin/E2F1	-0.053	0.18	-9999	-0.61	45	45
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.11	0.2	-9999	-0.47	107	107
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.25	-9999	-0.56	134	134
NT-4/5 (dimer)/p75(NTR)	-0.029	0.13	-9999	-0.57	27	27
IKBKB	0.014	0	-9999	-10000	0	0
AKT1	-0.07	0.2	-9999	-0.45	104	104
IKBKG	0.014	0	-9999	-10000	0	0
BDNF	-0.038	0.18	-9999	-0.69	38	38
MGDIs/NGR/p75(NTR)/LINGO1	-0.087	0.22	-9999	-0.61	69	69
FURIN	0.014	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.068	0.16	-9999	-0.55	37	37
LINGO1	-0.054	0.23	-9999	-0.81	43	43
Sortilin/TRAF6/NRIF	-0.01	0.05	-9999	-10000	0	0
proBDNF (dimer)	-0.038	0.18	-9999	-0.68	38	38
NTRK1	-0.059	0.23	-9999	-0.81	46	46
RTN4R	-0.02	0.16	-9999	-0.81	21	21
neuron apoptosis	-0.062	0.18	-9999	-0.56	26	26
IRAK1	0.014	0	-9999	-10000	0	0
SHC1	-0.097	0.23	-9999	-0.54	104	104
ARHGDIA	0.014	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.002	0.028	-9999	-0.45	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.12	0.21	-9999	-0.5	107	107
MAGEH1	0.012	0.036	-9999	-0.81	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.13	0.22	-9999	-0.51	108	108
Mammalian IAPs/DIABLO	-0.032	0.14	-9999	-0.6	28	28
proNGF (dimer)	-0.14	0.31	-9999	-0.79	98	98
MAGED1	0.008	0.062	-9999	-0.69	4	4
APP	0.012	0.036	-9999	-0.81	1	1
NT-4/5 (dimer)	0.009	0.057	-9999	-0.73	3	3
ZNF274	0.014	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.077	0.2	-9999	-0.46	104	104
NGF	-0.14	0.32	-9999	-0.79	98	98
cell cycle arrest	-0.1	0.22	-9999	-0.5	106	106
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.03	0.12	-9999	-0.53	1	1
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.11	-9999	-0.57	17	17
NCSTN	0.014	0	-9999	-10000	0	0
mol:GTP	-0.12	0.22	-9999	-0.54	104	104
PSENEN	0.01	0.051	-9999	-0.81	2	2
mol:ceramide	-0.093	0.22	-9999	-0.5	106	106
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.01	0.1	-9999	-0.41	1	1
p75(NTR)/beta APP	-0.028	0.12	-9999	-0.54	27	27
BEX1	-0.044	0.2	-9999	-0.81	35	35
mol:GDP	-0.11	0.23	-9999	-0.51	123	123
NGF (dimer)	-0.26	0.29	-9999	-0.56	238	238
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.08	0.2	-9999	-0.56	69	69
PIK3R1	0.011	0.037	-9999	-0.58	2	2
RAC1/GTP	-0.1	0.19	-9999	-0.47	104	104
MYD88	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.22	-9999	-0.54	104	104
RHOB	0.014	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.046	0.16	-9999	-0.62	39	39
NT3 (dimer)	-0.16	0.27	-9999	-0.58	154	154
TP53	-0.014	0.15	-9999	-0.55	5	5
PRDM4	-0.094	0.22	-9999	-0.5	106	106
BDNF (dimer)	-0.52	0.34	-9999	-0.66	404	404
PIK3CA	0.014	0	-9999	-10000	0	0
SORT1	-0.009	0.11	-9999	-0.58	20	20
activation of caspase activity	-0.11	0.2	-9999	-0.47	107	107
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.12	0.21	-9999	-0.5	106	106
RHOC	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
MAPK10	-0.061	0.19	-9999	-0.52	26	26
DIABLO	0.014	0	-9999	-10000	0	0
SMPD2	-0.094	0.22	-9999	-0.5	106	106
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.13	0.23	-9999	-0.55	106	106
PSEN1	0.014	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.018	-9999	-0.42	1	1
NT3 (dimer)/p75(NTR)	-0.15	0.22	-9999	-0.45	172	172
MAPK8	-0.052	0.19	-9999	-0.54	18	18
MAPK9	-0.049	0.18	-9999	-0.53	17	17
APAF1	0.012	0.026	-9999	-0.58	1	1
NTF3	-0.16	0.27	-9999	-0.58	154	154
NTF4	0.009	0.057	-9999	-0.73	3	3
NDN	0.003	0.077	-9999	-0.58	9	9
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.094	0.17	-9999	-0.42	104	104
p75 CTF/Sortilin/TRAF6/NRIF	-0.013	0.062	-9999	-10000	0	0
RhoA-B-C/GTP	-0.12	0.22	-9999	-0.53	104	104
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.056	0.14	-9999	-0.47	37	37
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.061	0.15	-9999	-0.5	37	37
PRKACB	0.012	0.026	-9999	-0.58	1	1
proBDNF (dimer)/p75 ECD	-0.039	0.14	-9999	-0.51	40	40
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.023	0.17	-9999	-0.81	23	23
BIRC2	-0.005	0.12	-9999	-0.81	12	12
neuron projection morphogenesis	-0.098	0.2	-9999	-0.45	104	104
BAD	-0.045	0.18	-9999	-0.51	17	17
RIPK2	0.014	0	-9999	-10000	0	0
NGFR	-0.023	0.16	-9999	-0.71	26	26
CYCS	-0.084	0.22	-9999	-0.47	106	106
ADAM17	0.011	0.037	-9999	-0.58	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.11	0.2	-9999	-0.49	104	104
BCL2L11	-0.045	0.18	-9999	-0.51	17	17
BDNF (dimer)/p75(NTR)	-0.064	0.17	-9999	-0.52	64	64
PI3K	-0.11	0.2	-9999	-0.49	104	104
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.12	0.21	-9999	-0.5	106	106
NDNL2	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
PRKCI	0.014	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.25	-9999	-0.59	123	123
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.12	0.22	-9999	-0.51	106	106
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
PRKCZ	0.012	0.026	-9999	-0.58	1	1
PLG	-0.006	0.079	-9999	-0.81	5	5
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.099	0.22	-9999	-0.59	33	33
SQSTM1	0.014	0	-9999	-10000	0	0
NGFRAP1	0.01	0.051	-9999	-0.81	2	2
CASP3	-0.039	0.17	-9999	-0.47	16	16
E2F1	-0.048	0.22	-9999	-0.81	39	39
CASP9	0.014	0	-9999	-10000	0	0
IKK complex	-0.1	0.17	-9999	-0.71	8	8
NGF (dimer)/TRKA	-0.17	0.28	-9999	-0.63	137	137
MMP7	-0.27	0.39	-9999	-0.8	183	183
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.11	0.2	-9999	-0.47	106	106
MMP3	-0.53	0.38	-9999	-0.8	348	348
APAF-1/Caspase 9	-0.1	0.18	-9999	-0.69	19	19

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.39	-9999	-1.1	51	51
PCK1	-0.5	0.62	-9999	-1.3	177	177
HNF4A	-0.31	0.48	-9999	-1.3	61	61
KCNJ11	-0.35	0.52	-9999	-1.2	113	113
AKT1	-0.082	0.15	-9999	-10000	0	0
response to starvation	-0.004	0.023	-9999	-10000	0	0
DLK1	-0.44	0.57	-9999	-1.2	140	140
NKX2-1	-0.1	0.34	-9999	-0.82	57	57
ACADM	-0.25	0.4	-9999	-1.1	54	54
TAT	-0.15	0.24	-9999	-0.85	21	21
CEBPB	0.014	0.004	-9999	-10000	0	0
CEBPA	0.011	0.045	-9999	-0.58	3	3
TTR	-0.3	0.33	-9999	-0.99	59	59
PKLR	-0.29	0.44	-9999	-1.1	81	81
APOA1	-0.3	0.46	-9999	-1.3	49	49
CPT1C	-0.25	0.4	-9999	-1.1	54	54
ALAS1	-0.087	0.17	-9999	-10000	0	0
TFRC	-0.22	0.3	-9999	-0.91	35	35
FOXF1	0.019	0.1	-9999	-0.72	7	7
NF1	0.021	0	-9999	-10000	0	0
HNF1A (dimer)	-0.002	0.12	-9999	-0.8	10	10
CPT1A	-0.24	0.39	-9999	-1.1	51	51
HMGCS1	-0.24	0.39	-9999	-1.1	53	53
NR3C1	0.019	0.024	-9999	-10000	0	0
CPT1B	-0.25	0.4	-9999	-1.1	52	52
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.012	0.026	-9999	-10000	0	0
GCK	-0.28	0.42	-9999	-1.1	60	60
CREB1	-0.037	0.083	-9999	-10000	0	0
IGFBP1	-0.1	0.2	-9999	-0.84	17	17
PDX1	-0.12	0.22	-9999	-0.79	22	22
UCP2	-0.24	0.39	-9999	-1.1	55	55
ALDOB	-0.27	0.43	-9999	-1.2	60	60
AFP	-0.2	0.25	-9999	-0.7	62	62
BDH1	-0.24	0.39	-9999	-1.1	51	51
HADH	-0.25	0.41	-9999	-1.1	52	52
F2	-0.32	0.47	-9999	-1.3	53	53
HNF1A	-0.002	0.12	-9999	-0.8	10	10
G6PC	-0.061	0.14	-9999	-0.68	3	3
SLC2A2	-0.14	0.22	-9999	-0.73	8	8
INS	-0.012	0.056	-9999	-0.83	2	2
FOXA1	-0.21	0.3	-9999	-0.59	193	193
FOXA3	-0.15	0.29	-9999	-0.91	56	56
FOXA2	-0.3	0.46	-9999	-1.2	61	61
ABCC8	-0.26	0.41	-9999	-1.1	54	54
ALB	-0.23	0.3	-9999	-0.82	76	76

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.004	0.047	-9999	-0.63	3	3
Metarhodopsin II/Arrestin	-0.004	0.048	-9999	-0.55	4	4
PDE6G/GNAT1/GTP	-0.019	0.1	-9999	-0.55	18	18
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.062	-9999	-0.81	3	3
GRK1	0	0.05	-9999	-0.81	2	2
CNG Channel	-0.4	0.28	-9999	-0.64	247	247
mol:Na +	-0.3	0.26	-9999	-0.8	57	57
mol:ADP	0	0.05	-9999	-0.81	2	2
RGS9-1/Gbeta5/R9AP	-0.018	0.089	-9999	-0.53	10	10
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.31	0.27	-9999	-0.84	57	57
CNGB1	-0.42	0.41	-9999	-0.8	273	273
RDH5	0.011	0.044	-9999	-0.69	2	2
SAG	0.002	0.005	-9999	-10000	0	0
mol:Ca2+	-0.27	0.27	-9999	-0.77	57	57
Na + (4 Units)	-0.28	0.24	-9999	-0.74	57	57
RGS9	-0.005	0.12	-9999	-0.77	12	12
GNB1/GNGT1	-0.11	0.24	-9999	-0.62	94	94
GNAT1/GDP	-0.018	0.092	-9999	-0.54	11	11
GUCY2D	-0.029	0.18	-9999	-0.81	27	27
GNGT1	-0.14	0.32	-9999	-0.81	94	94
GUCY2F	0	0.05	-9999	-0.81	2	2
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.16	0.21	-9999	-0.58	53	53
mol:11-cis-retinal	0.011	0.044	-9999	-0.69	2	2
mol:cGMP	-0.08	0.19	-9999	-0.5	81	81
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.007	0.063	-9999	-0.59	6	6
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.028	0.15	-9999	-0.58	37	37
Metarhodopsin II	-0.006	0.054	-9999	-0.5	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.083	0.2	-9999	-0.52	80	80
RGS9BP	0.002	0.081	-9999	-0.58	10	10
Metarhodopsin II/Transducin	-0.039	0.12	-9999	-0.28	100	100
GCAP Family/Ca ++	-0.058	0.16	-9999	-0.51	57	57
PDE6A/B	-0.22	0.24	-9999	-0.46	253	253
mol:Pi	-0.018	0.089	-9999	-0.53	10	10
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.092	0.19	-9999	-0.5	97	97
PDE6B	-0.043	0.19	-9999	-0.68	42	42
PDE6A	-0.25	0.29	-9999	-0.58	233	233
PDE6G	-0.01	0.14	-9999	-0.81	15	15
RHO	-0.002	0.071	-9999	-0.81	4	4
PDE6	-0.17	0.2	-9999	-0.65	39	39
GUCA1A	-0.075	0.25	-9999	-0.81	56	56
GC2/GCAP Family	-0.06	0.17	-9999	-0.51	58	58
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.006	0.072	-9999	-0.65	6	6

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.016	0.13	-9999	-0.63	23	23
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.043	0.13	-9999	-0.42	53	53
STXBP1	0.014	0	-9999	-10000	0	0
ACh/CHRNA1	-0.16	0.22	-9999	-0.45	186	186
RAB3GAP2/RIMS1/UNC13B	-0.036	0.11	-9999	-0.53	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.048	0.17	-9999	-0.58	50	50
mol:ACh	-0.004	0.041	-9999	-0.12	59	59
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.051	0.11	-9999	-0.4	27	27
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.16	0.22	-9999	-0.44	186	186
UNC13B	0.01	0.045	-9999	-0.58	3	3
CHRNA1	-0.22	0.32	-9999	-0.65	186	186
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.14	0.25	-9999	-0.57	127	127
SNAP25	-0.014	0.079	-9999	-0.3	37	37
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.18	0.35	-9999	-0.8	127	127
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.006	0.12	-9999	-0.54	23	23
STX1A/SNAP25 fragment 1/VAMP2	-0.051	0.11	-9999	-0.4	27	27

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.014	0.036	-9999	-10000	0	0
NFATC2	-0.061	0.13	-9999	-0.4	61	61
NFATC3	-0.014	0.036	-9999	-10000	0	0
CD40LG	-0.32	0.34	-9999	-0.83	112	112
PTGS2	-0.34	0.36	-9999	-0.86	127	127
JUNB	0.014	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.016	0.016	-9999	-10000	0	0
CaM/Ca2+	-0.016	0.016	-9999	-10000	0	0
CALM1	0.004	0.011	-9999	-10000	0	0
JUN	0.004	0.011	-9999	-10000	0	0
mol:Ca2+	-0.017	0.014	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.004	-9999	-10000	0	0
FOSL1	-0.005	0.12	-9999	-0.79	12	12
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.16	0.16	-9999	-0.61	21	21
FOS	-0.073	0.2	-9999	-0.59	67	67
IFNG	-0.36	0.38	-9999	-0.86	140	140
AP-1/NFAT1-c-4	-0.38	0.37	-9999	-1	82	82
FASLG	-0.31	0.34	-9999	-0.86	91	91
NFAT1-c-4/ICER1	-0.1	0.12	-9999	-0.47	17	17
IL2RA	-0.32	0.35	-9999	-0.87	99	99
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.42	-9999	-0.81	293	293
JunB/Fra1/NFAT1-c-4	-0.1	0.13	-9999	-0.58	16	16
IL4	-0.3	0.31	-9999	-0.8	81	81
IL2	-0.009	0.034	-9999	-0.67	1	1
IL3	-0.028	0.023	-9999	-10000	0	0
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	0.007	0.072	-9999	-0.81	4	4
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.002	-9999	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.021	0.097	-10000	0	-0.54	12	12
fibroblast growth factor receptor signaling pathway	-0.021	0.097	-10000	0	-0.54	12	12
LAMA1	-0.35	0.41	-10000	0	-0.8	231	231
PRNP	0.012	0.036	-10000	0	-0.81	1	1
GPC1/SLIT2	-0.056	0.14	-10000	0	-0.43	68	68
SMAD2	0.033	0.034	-10000	0	-0.48	1	1
GPC1/PrPc/Cu2+	-0.003	0.037	-10000	0	-0.48	3	3
GPC1/Laminin alpha1	-0.27	0.31	-10000	0	-0.62	231	231
TDGF1	-0.002	0.087	-10000	0	-0.81	6	6
CRIPTO/GPC1	-0.009	0.073	-10000	0	-0.59	8	8
APP/GPC1	-0.003	0.042	-10000	0	-0.55	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.017	0.066	-10000	0	-0.51	8	8
FLT1	0.012	0.036	-10000	0	-0.81	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.003	0.035	-10000	0	-0.53	1	1
SERPINC1	-0.005	0.12	-10000	0	-0.81	11	11
FYN	0.016	0.07	-10000	0	-0.53	8	8
FGR	0.016	0.07	-10000	0	-0.53	8	8
positive regulation of MAPKKK cascade	0.008	0.11	-10000	0	-0.45	11	11
SLIT2	-0.063	0.2	-10000	0	-0.58	67	67
GPC1/NRG	-0.097	0.22	-10000	0	-0.6	84	84
NRG1	-0.11	0.3	-10000	0	-0.79	82	82
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.01	0.071	-10000	0	-0.53	9	9
LYN	0.016	0.07	-10000	0	-0.53	8	8
mol:Spermine	0.01	0.034	-10000	0	-0.53	2	2
cell growth	-0.021	0.097	-10000	0	-0.54	12	12
BMP signaling pathway	-0.011	0.044	0.69	2	-10000	0	2
SRC	0.017	0.066	-10000	0	-0.51	8	8
TGFBR1	0.014	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.37	0.28	-10000	0	-0.58	333	333
GPC1	0.011	0.044	-10000	0	-0.69	2	2
TGFBR1 (dimer)	0.014	0	-10000	0	-10000	0	0
VEGFA	0.002	0.095	-10000	0	-0.81	7	7
BLK	-0.061	0.2	-10000	0	-0.54	71	71
HCK	0.013	0.094	-10000	0	-0.64	9	9
FGF2	-0.008	0.12	-10000	0	-0.63	17	17
FGFR1	0.003	0.091	-10000	0	-0.77	7	7
VEGFR1 homodimer	0.012	0.036	-10000	0	-0.81	1	1
TGFBR2	0.011	0.037	-10000	0	-0.58	2	2
cell death	-0.003	0.042	-10000	0	-0.55	3	3
ATIII/GPC1	-0.015	0.094	-10000	0	-0.6	13	13
PLA2G2A/GPC1	-0.27	0.2	-10000	0	-0.42	334	334
LCK	0.004	0.11	-10000	0	-0.54	19	19
neuron differentiation	-0.097	0.22	-10000	0	-0.6	84	84
PrPc/Cu2+	-0.001	0.027	-10000	0	-0.63	1	1
APP	0.012	0.036	-10000	0	-0.81	1	1
TGFBR2 (dimer)	0.011	0.036	-10000	0	-0.58	2	2

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.002	0.051	-9999	-0.58	3	3
SVIL	0.002	0.035	-9999	-0.58	1	1
ZNF318	0.04	0.061	-9999	-10000	0	0
JMJD2C	0.007	0.022	-9999	-0.1	15	15
T-DHT/AR/Ubc9	-0.12	0.18	-9999	-0.4	140	140
CARM1	0.012	0.003	-9999	-10000	0	0
PRDX1	0.015	0.004	-9999	-10000	0	0
PELP1	0.018	0.01	-9999	-10000	0	0
CTNNB1	0.004	0.032	-9999	-0.58	1	1
AKT1	0.021	0.017	-9999	-10000	0	0
PTK2B	0.005	0.03	-9999	-0.58	1	1
MED1	0.02	0.041	-9999	-0.81	1	1
MAK	0.027	0.12	-9999	-0.71	9	9
response to oxidative stress	0.002	0.004	-9999	-10000	0	0
HIP1	0.002	0.035	-9999	-0.58	1	1
GSN	0.002	0.026	-9999	-10000	0	0
NCOA2	-0.036	0.16	-9999	-0.58	42	42
NCOA6	0.002	0.042	-9999	-0.81	1	1
DNA-PK	0.031	0.066	-9999	-10000	0	0
NCOA4	0.011	0.026	-9999	-0.58	1	1
PIAS3	0.005	0.019	-9999	-10000	0	0
cell proliferation	-0.012	0.1	-9999	-0.6	8	8
XRCC5	0.019	0.013	-9999	-10000	0	0
UBE3A	-0.003	0.038	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.13	0.2	-9999	-0.42	154	154
FHL2	-0.018	0.11	-9999	-0.95	2	2
RANBP9	0.004	0.023	-9999	-10000	0	0
JMJD1A	-0.057	0.075	-9999	-0.13	250	250
CDK6	0.002	0.098	-9999	-0.78	8	8
TGFB1I1	-0.021	0.14	-9999	-0.82	15	15
T-DHT/AR/CyclinD1	-0.13	0.2	-9999	-0.43	149	149
XRCC6	0.019	0.013	-9999	-10000	0	0
T-DHT/AR	-0.14	0.2	-9999	-0.47	107	107
CTDSP1	0.011	0.005	-9999	-10000	0	0
CTDSP2	0.032	0.042	-9999	-10000	0	0
BRCA1	0.003	0.024	-9999	-10000	0	0
TCF4	0.027	0.03	-9999	-10000	0	0
CDKN2A	-0.33	0.39	-9999	-0.75	238	238
SRF	0.03	0.022	-9999	-10000	0	0
NKX3-1	-0.14	0.15	-9999	-0.77	9	9
KLK3	-0.22	0.54	-9999	-1.4	92	92
TMF1	0.011	0.005	-9999	-10000	0	0
HNRNPA1	0.025	0.025	-9999	-10000	0	0
AOF2	-0.012	0.027	-9999	-0.07	88	88
APPL1	0.041	0.037	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.11	0.18	-9999	-0.4	129	129
AR	-0.17	0.27	-9999	-0.61	140	140
UBA3	0.011	0.005	-9999	-10000	0	0
PATZ1	0.025	0.025	-9999	-10000	0	0
PAWR	0.011	0.005	-9999	-10000	0	0
PRKDC	0.019	0.013	-9999	-10000	0	0
PA2G4	0.026	0.027	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.098	0.17	-9999	-0.37	129	129
RPS6KA3	0	0.045	-9999	-0.58	2	2
T-DHT/AR/ARA70	-0.12	0.18	-9999	-0.4	141	141
LATS2	0.023	0.022	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.092	0.17	-9999	-0.37	129	129
Cyclin D3/CDK11 p58	0.003	0.007	-9999	-10000	0	0
VAV3	-0.036	0.15	-9999	-0.59	36	36
KLK2	-0.074	0.14	-9999	-0.75	15	15
CASP8	0.017	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.13	0.19	-9999	-0.44	104	104
TMPRSS2	-0.5	0.5	-9999	-1	243	243
CCND1	-0.009	0.12	-9999	-0.76	13	13
PIAS1	-0.003	0.038	-9999	-10000	0	0
mol:T-DHT	-0.023	0.035	-9999	-0.067	164	164
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.012	0.057	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.12	0.2	-9999	-0.42	137	137
CMTM2	-0.008	0.14	-9999	-0.8	15	15
SNURF	-0.014	0.12	-9999	-0.58	23	23
ZMIZ1	-0.005	0.029	-9999	-10000	0	0
CCND3	0.014	0.002	-9999	-10000	0	0
TGIF1	0.023	0.044	-9999	-0.81	1	1
FKBP4	0.004	0.023	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.27	0.23	-10000	0	-0.94	14	14
IHH	-0.054	0.074	-10000	0	-0.76	3	3
SHH Np/Cholesterol/GAS1	-0.043	0.14	-10000	0	-0.48	46	46
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.042	0.14	0.48	46	-10000	0	46
SMO/beta Arrestin2	-0.14	0.15	-10000	0	-0.59	25	25
SMO	-0.16	0.16	-10000	0	-0.63	25	25
AKT1	-0.059	0.083	-10000	0	-0.6	2	2
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	-0.04	0.17	-10000	0	-0.58	47	47
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.15	0.16	-10000	0	-0.62	25	25
STIL	-0.13	0.17	-10000	0	-0.63	32	32
DHH N/PTCH2	-0.015	0.087	-10000	0	-0.51	15	15
DHH N/PTCH1	-0.14	0.14	-10000	0	-0.77	9	9
PIK3CA	0.014	0	-10000	0	-10000	0	0
DHH	0.009	0.051	-10000	0	-0.81	2	2
PTHLH	-0.45	0.33	-10000	0	-0.65	369	369
determination of left/right symmetry	-0.15	0.16	-10000	0	-0.62	25	25
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
skeletal system development	-0.44	0.33	-10000	0	-0.65	369	369
IHH N/Hhip	-0.054	0.17	-10000	0	-0.67	34	34
DHH N/Hhip	-0.039	0.15	-10000	0	-0.61	33	33
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.15	0.16	-10000	0	-0.62	25	25
pancreas development	-0.037	0.19	-10000	0	-0.8	31	31
HHAT	0.014	0	-10000	0	-10000	0	0
PI3K	-0.002	0.026	-10000	0	-0.42	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.002	0.091	-10000	0	-0.72	8	8
somite specification	-0.15	0.16	-10000	0	-0.62	25	25
SHH Np/Cholesterol/PTCH1	-0.14	0.17	-10000	0	-0.6	44	44
SHH Np/Cholesterol/PTCH2	-0.045	0.15	-10000	0	-0.5	47	47
SHH Np/Cholesterol/Megalin	-0.061	0.18	-10000	0	-0.55	58	58
SHH	-0.028	0.17	-10000	0	-0.62	38	38
catabolic process	-0.16	0.16	-10000	0	-0.73	11	11
SMO/Vitamin D3	-0.15	0.18	-10000	0	-0.64	33	33
SHH Np/Cholesterol/Hhip	-0.065	0.18	-10000	0	-0.55	60	60
LRP2	-0.031	0.18	-10000	0	-0.81	27	27
receptor-mediated endocytosis	-0.17	0.17	-10000	0	-0.61	47	47
SHH Np/Cholesterol/BOC	-0.065	0.15	-10000	0	-0.5	39	39
SHH Np/Cholesterol/CDO	-0.044	0.14	-10000	0	-0.49	38	38
mesenchymal cell differentiation	0.064	0.18	0.55	60	-10000	0	60
mol:Vitamin D3	-0.14	0.17	-10000	0	-0.6	44	44
IHH N/PTCH2	-0.025	0.099	-10000	0	-0.56	16	16
CDON	-0.001	0.092	-10000	0	-0.58	13	13
IHH N/PTCH1	-0.16	0.16	-10000	0	-0.73	11	11
Megalin/LRPAP1	-0.032	0.14	-10000	0	-0.62	27	27
PTCH2	-0.004	0.11	-10000	0	-0.67	13	13
SHH Np/Cholesterol	-0.033	0.13	-10000	0	-0.5	38	38
PTCH1	-0.16	0.16	-10000	0	-0.73	11	11
HHIP	-0.038	0.19	-10000	0	-0.8	31	31

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.21	0.26	-9999	-0.52	198	198
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.055	0.21	-9999	-0.7	49	49
SMAD9	-0.076	0.17	-9999	-0.58	45	45
SMAD4	0.012	0.026	-9999	-0.58	1	1
SMAD5	-0.051	0.14	-9999	-0.48	27	27
BMP7/USAG1	-0.16	0.24	-9999	-0.5	161	161
SMAD5/SKI	-0.041	0.14	-9999	-0.47	21	21
SMAD1	0.041	0.027	-9999	-10000	0	0
BMP2	-0.018	0.16	-9999	-0.8	20	20
SMAD1/SMAD1/SMAD4	0	0.011	-9999	-10000	0	0
BMPR1A	0.011	0.037	-9999	-0.58	2	2
BMPR1B	-0.062	0.23	-9999	-0.75	51	51
BMPR1A-1B/BAMBI	-0.063	0.16	-9999	-0.48	68	68
AHSG	-0.04	0.2	-9999	-0.81	32	32
CER1	-0.006	0.087	-9999	-0.81	6	6
BMP2-4/CER1	-0.034	0.13	-9999	-0.55	26	26
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.093	0.19	-9999	-0.54	51	51
BMP2-4 (homodimer)	-0.032	0.13	-9999	-0.56	30	30
RGMB	0.014	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.05	0.14	-9999	-0.49	45	45
RGMA	-0.055	0.19	-9999	-0.58	60	60
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.093	0.18	-9999	-0.5	51	51
BMP2-4/USAG1	-0.13	0.21	-9999	-0.57	55	55
SMAD6/SMURF1/SMAD5	-0.041	0.14	-9999	-0.46	23	23
SOSTDC1	-0.16	0.29	-9999	-0.63	142	142
BMP7/BMPR2/BMPR1A-1B	-0.068	0.16	-9999	-0.51	42	42
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.084	-9999	-0.77	6	6
HFE2	-0.18	0.27	-9999	-0.58	162	162
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.044	0.14	-9999	-0.55	36	36
SMAD5/SMAD5/SMAD4	-0.042	0.14	-9999	-0.47	23	23
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.094	0.13	-9999	-0.52	25	25
BMP7 (homodimer)	-0.032	0.16	-9999	-0.58	40	40
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.045	0.16	-9999	-0.61	38	38
SMAD1/SKI	0.047	0.026	-9999	-10000	0	0
SMAD6	0.014	0	-9999	-10000	0	0
CTDSP2	0.014	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.061	0.17	-9999	-0.55	52	52
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.34	0.41	-9999	-0.81	222	222
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.057	0.17	-9999	-0.57	52	52
CHRDL1	-0.29	0.29	-9999	-0.58	266	266
ENDOFIN/SMAD1	0.047	0.026	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.001	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	-0.008	0.12	-9999	-0.66	17	17
SMURF2	0.014	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.2	0.21	-9999	-0.76	25	25
BMP2-4/GREM1	-0.25	0.29	-9999	-0.56	231	231
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.056	0.17	-9999	-0.54	46	46
SMAD1/SMAD6	0.047	0.026	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.032	0.16	-9999	-0.58	40	40
BMP6	0.004	0.084	-9999	-0.77	6	6
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.075	0.16	-9999	-0.43	51	51
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.047	0.026	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.16	0.22	-9999	-0.5	110	110
CHRD	-0.012	0.14	-9999	-0.78	17	17
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.1	0.19	-9999	-0.53	51	51
BMP4	0.001	0.088	-9999	-0.6	11	11
FST	-0.25	0.38	-9999	-0.81	169	169
BMP2-4/NOG	-0.069	0.18	-9999	-0.55	47	47
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.063	0.15	-9999	-0.48	42	42

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.039	0.18	-10000	0	-0.4	88	88
ACTA1	-0.14	0.23	-10000	0	-0.6	90	90
NUMA1	-0.039	0.18	-10000	0	-0.4	88	88
SPTAN1	-0.062	0.23	-10000	0	-0.53	88	88
LIMK1	-0.062	0.23	-10000	0	-0.53	88	88
BIRC3	-0.023	0.17	-10000	0	-0.81	23	23
BIRC2	-0.005	0.12	-10000	0	-0.81	12	12
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.095	0.29	-10000	0	-0.7	91	91
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.038	0.18	-10000	0	-0.4	88	88
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.061	0.22	-10000	0	-0.52	88	88
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.062	0.23	-10000	0	-0.53	88	88
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	0.002	0.088	-10000	0	-0.53	7	7
BID	-0.028	0.12	-10000	0	-0.28	88	88
MAP3K1	-0.011	0.074	-10000	0	-0.21	31	31
TRADD	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.004	0.02	-10000	0	-0.41	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.062	0.23	-10000	0	-0.53	88	88
CASP9	0.014	0.001	-10000	0	-10000	0	0
DNA repair	0.006	0.063	-10000	0	-0.2	12	12
neuron apoptosis	0.018	0.026	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.054	0.22	-10000	0	-0.52	83	83
APAF1	0.012	0.026	-10000	0	-0.58	1	1
CASP6	-0.002	0.1	-10000	0	-0.46	3	3
TRAF2	0.004	0.088	-10000	0	-0.81	6	6
ICAD/CAD	-0.054	0.22	-10000	0	-0.53	83	83
CASP7	0.006	0.064	0.3	19	-10000	0	19
KRT18	0.003	0.065	-10000	0	-0.42	9	9
apoptosis	-0.044	0.21	-10000	0	-0.48	84	84
DFFA	-0.062	0.23	-10000	0	-0.53	88	88
DFFB	-0.064	0.23	-10000	0	-0.54	88	88
PARP1	-0.006	0.063	0.2	12	-10000	0	12
actin filament polymerization	0.049	0.21	0.5	83	-10000	0	83
TNF	-0.024	0.17	-10000	0	-0.77	25	25
CYCS	-0.018	0.093	-10000	0	-0.27	36	36
SATB1	-0.009	0.12	-10000	0	-0.48	8	8
SLK	-0.062	0.23	-10000	0	-0.53	88	88
p15 BID/BAX	-0.018	0.11	-10000	0	-0.32	33	33
CASP2	0.033	0.073	-10000	0	-10000	0	0
JNK cascade	0.011	0.074	0.21	31	-10000	0	31
CASP3	-0.074	0.24	-10000	0	-0.57	88	88
LMNB2	0.027	0.06	-10000	0	-0.35	3	3
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	0.011	0.037	-10000	0	-0.58	2	2
Mammalian IAPs/DIABLO	-0.032	0.14	-10000	0	-0.6	28	28
negative regulation of DNA binding	0.002	0.087	-10000	0	-0.52	7	7
stress fiber formation	-0.061	0.22	-10000	0	-0.52	88	88
GZMB	-0.12	0.33	-10000	0	-0.79	91	91
CASP1	0.016	0.041	-10000	0	-0.59	2	2
LMNB1	0.027	0.06	-10000	0	-0.35	3	3
APP	0.018	0.027	-10000	0	-10000	0	0
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	-0.048	0.2	-10000	0	-0.46	87	87
LMNA	0.027	0.06	-10000	0	-0.35	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.026	0.078	-10000	0	-0.36	10	10
LRDD	0.012	0.036	-10000	0	-0.81	1	1
SREBF1	-0.062	0.23	-10000	0	-0.53	88	88
APAF-1/Caspase 9	0	0.079	0.45	11	-10000	0	11
nuclear fragmentation during apoptosis	-0.038	0.17	-10000	0	-0.4	88	88
CFL2	-0.051	0.22	-10000	0	-0.51	83	83
GAS2	-0.1	0.25	-10000	0	-0.57	90	90
positive regulation of apoptosis	0.031	0.06	-10000	0	-0.34	3	3
PRF1	-0.047	0.21	-10000	0	-0.79	39	39

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.11	0.31	-10000	0	-0.91	64	64
NFATC2	-0.041	0.23	-10000	0	-0.72	30	30
NFATC3	-0.008	0.061	-10000	0	-10000	0	0
CD40LG	-0.35	0.41	-10000	0	-1	77	77
ITCH	0.018	0.09	-10000	0	-10000	0	0
CBLB	0.018	0.09	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.34	0.45	-10000	0	-1.1	118	118
JUNB	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.034	0.092	-10000	0	-10000	0	0
T cell anergy	-0.006	0.16	-10000	0	-0.53	17	17
TLE4	-0.011	0.17	-10000	0	-0.64	16	16
Jun/NFAT1-c-4/p21SNFT	-0.17	0.23	-10000	0	-0.96	20	20
AP-1/NFAT1-c-4	-0.36	0.44	-10000	0	-1.1	81	81
IKZF1	-0.019	0.2	-10000	0	-0.74	22	22
T-helper 2 cell differentiation	-0.072	0.23	-10000	0	-0.78	26	26
AP-1/NFAT1	-0.14	0.19	-10000	0	-0.6	45	45
CALM1	0.008	0.059	-10000	0	-10000	0	0
EGR2	-0.063	0.3	-10000	0	-1.4	16	16
EGR3	-0.053	0.26	-10000	0	-1.2	14	14
NFAT1/FOXP3	-0.13	0.33	-10000	0	-0.8	82	82
EGR1	-0.014	0.13	-10000	0	-0.58	25	25
JUN	-0.019	0.035	-10000	0	-10000	0	0
EGR4	-0.079	0.26	-10000	0	-0.78	60	60
mol:Ca2+	-0.007	0.063	-10000	0	-10000	0	0
GBP3	-0.026	0.21	-10000	0	-0.7	30	30
FOSL1	-0.005	0.12	-10000	0	-0.79	12	12
NFAT1-c-4/MAF/IRF4	-0.12	0.25	-10000	0	-0.94	24	24
DGKA	-0.009	0.17	-10000	0	-0.61	15	15
CREM	0.013	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.22	0.27	-10000	0	-0.95	31	31
CTLA4	-0.16	0.41	-10000	0	-0.89	108	108
NFAT1-c-4 (dimer)/EGR1	-0.11	0.25	-10000	0	-1	21	21
NFAT1-c-4 (dimer)/EGR4	-0.15	0.28	-10000	0	-0.92	32	32
FOS	-0.097	0.2	-10000	0	-0.6	67	67
IFNG	-0.22	0.34	-10000	0	-0.86	73	73
T cell activation	-0.11	0.2	-10000	0	-0.72	11	11
MAF	0.008	0.058	-10000	0	-0.58	5	5
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.038	0.16	0.72	11	-10000	0	11
TNF	-0.13	0.31	-10000	0	-0.95	39	39
FASLG	-0.12	0.39	-10000	0	-1.3	34	34
TBX21	-0.041	0.19	-10000	0	-0.78	29	29
BATF3	0.007	0.072	-10000	0	-0.81	4	4
PRKCQ	0	0.094	-10000	0	-0.62	11	11
PTPN1	-0.009	0.17	-10000	0	-0.58	19	19
NFAT1-c-4/ICER1	-0.1	0.22	-10000	0	-0.96	17	17
GATA3	-0.016	0.15	-10000	0	-0.77	20	20
T-helper 1 cell differentiation	-0.2	0.34	-10000	0	-0.84	73	73
IL2RA	-0.3	0.38	-10000	0	-0.96	103	103
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.009	0.17	-10000	0	-0.61	15	15
E2F1	-0.041	0.22	-10000	0	-0.8	39	39
PPARG	-0.21	0.29	-10000	0	-0.58	197	197
SLC3A2	-0.009	0.17	-10000	0	-0.61	15	15
IRF4	-0.038	0.19	-10000	0	-0.75	35	35
PTGS2	-0.37	0.44	-10000	0	-1.1	88	88
CSF2	-0.53	0.5	-10000	0	-1	206	206
JunB/Fra1/NFAT1-c-4	-0.1	0.22	-10000	0	-0.93	18	18
IL4	-0.076	0.24	-10000	0	-0.85	23	23
IL5	-0.32	0.37	-10000	0	-1	58	58
IL2	-0.11	0.2	-10000	0	-0.75	10	10
IL3	-0.063	0.051	-10000	0	-10000	0	0
RNF128	-0.034	0.23	-10000	0	-0.65	63	63
NFATC1	-0.038	0.16	-10000	0	-0.72	11	11
CDK4	0.022	0.14	0.65	3	-10000	0	3
PTPRK	-0.009	0.17	-10000	0	-0.61	15	15
IL8	-0.39	0.46	-10000	0	-1.1	119	119
POU2F1	0.014	0.002	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.023	0.16	-10000	0	-0.41	26	26
CRKL	-0.021	0.15	-10000	0	-0.4	62	62
HRAS	-0.012	0.16	-10000	0	-0.58	9	9
mol:PIP3	-0.034	0.14	-10000	0	-0.4	61	61
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.011	0.037	-10000	0	-0.58	2	2
GAB1	-0.03	0.16	-10000	0	-0.43	61	61
FOXO3	-0.013	0.14	-10000	0	-0.42	8	8
AKT1	-0.023	0.15	-10000	0	-0.4	61	61
BAD	-0.013	0.14	-10000	0	-0.37	55	55
megakaryocyte differentiation	-0.04	0.17	-10000	0	-0.43	73	73
GSK3B	-0.013	0.14	-10000	0	-0.37	55	55
RAF1	0.002	0.13	-10000	0	-0.46	8	8
SHC1	0.014	0	-10000	0	-10000	0	0
STAT3	-0.03	0.16	-10000	0	-0.43	61	61
STAT1	-0.11	0.37	-10000	0	-1	61	61
HRAS/SPRED1	-0.049	0.1	-10000	0	-0.46	8	8
cell proliferation	-0.033	0.16	-10000	0	-0.45	61	61
PIK3CA	0.013	0	-10000	0	-10000	0	0
TEC	-0.015	0.13	-10000	0	-0.58	25	25
RPS6KB1	-0.029	0.16	-10000	0	-0.43	62	62
HRAS/SPRED2	-0.05	0.11	-10000	0	-0.46	10	10
LYN/TEC/p62DOK	-0.069	0.15	-10000	0	-0.57	14	14
MAPK3	0.017	0.099	-10000	0	-0.33	5	5
STAP1	-0.063	0.19	-10000	0	-0.44	97	97
GRAP2	-0.002	0.1	-10000	0	-0.67	12	12
JAK2	-0.13	0.27	-10000	0	-0.84	61	61
STAT1 (dimer)	-0.1	0.36	-10000	0	-1	61	61
mol:Gleevec	0	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.085	0.17	-10000	0	-0.5	24	24
actin filament polymerization	-0.031	0.16	-10000	0	-0.43	62	62
LYN	0.012	0.036	-10000	0	-0.81	1	1
STAP1/STAT5A (dimer)	-0.071	0.23	-10000	0	-0.59	65	65
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
CBL/CRKL/GRB2	-0.005	0.14	-10000	0	-0.42	5	5
PI3K	-0.016	0.15	-10000	0	-0.41	61	61
PTEN	0.014	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.15	0.44	-10000	0	-1.3	63	63
MAPK8	-0.034	0.17	-10000	0	-0.46	61	61
STAT3 (dimer)	-0.029	0.15	-10000	0	-0.42	61	61
positive regulation of transcription	0.019	0.085	-10000	0	-0.28	3	3
mol:GDP	-0.071	0.14	-10000	0	-0.62	10	10
PIK3C2B	-0.03	0.16	-10000	0	-0.44	61	61
CBL/CRKL	-0.012	0.14	-10000	0	-0.38	56	56
FER	-0.031	0.16	-10000	0	-0.43	63	63
SH2B3	-0.031	0.16	-10000	0	-0.43	62	62
PDPK1	-0.025	0.13	-10000	0	-0.37	61	61
SNAI2	-0.041	0.17	-10000	0	-0.44	73	73
positive regulation of cell proliferation	-0.063	0.26	-10000	0	-0.74	61	61
KITLG	0.011	0.047	-10000	0	-0.6	3	3
cell motility	-0.063	0.26	-10000	0	-0.74	61	61
PTPN6	0.008	0.013	-10000	0	-10000	0	0
EPOR	-0.004	0.14	-10000	0	-0.67	11	11
STAT5A (dimer)	-0.046	0.22	-10000	0	-0.6	61	61
SOCS1	-0.039	0.2	-10000	0	-0.81	33	33
cell migration	0.039	0.17	0.44	69	-10000	0	69
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.077	0.26	-10000	0	-0.8	57	57
VAV1	0.003	0.081	-10000	0	-0.6	9	9
GRB10	-0.031	0.16	-10000	0	-0.43	62	62
PTPN11	0.014	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.04	0.16	-10000	0	-0.46	63	63
GO:0007205	0.001	0.009	-10000	0	-10000	0	0
MAP2K1	0.013	0.11	-10000	0	-0.37	5	5
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.12	0.44	-10000	0	-1.3	62	62
MAP2K2	0.013	0.11	-10000	0	-0.37	5	5
SHC/Grb2/SOS1	-0.055	0.13	-10000	0	-0.4	61	61
STAT5A	-0.048	0.22	-10000	0	-0.62	61	61
GRB2	0.014	0	-10000	0	-10000	0	0
response to radiation	-0.04	0.17	-10000	0	-0.43	73	73
SHC/GRAP2	-0.012	0.076	-10000	0	-0.5	12	12
PTPRO	-0.041	0.17	-10000	0	-0.44	73	73
SH2B2	-0.032	0.16	-10000	0	-0.44	62	62
DOK1	0.012	0.036	-10000	0	-0.81	1	1
MATK	-0.04	0.17	-10000	0	-0.45	69	69
CREBBP	0.034	0.015	-10000	0	-10000	0	0
BCL2	-0.007	0.18	-10000	0	-1	9	9

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.04	0.056	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.1	0.14	-9999	-0.45	38	38
JUN	-0.066	0.16	-9999	-0.47	39	39
HRAS	0.012	0.036	-9999	-0.81	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.25	-9999	-0.61	91	91
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.007	0.072	-9999	-0.81	4	4
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.24	-9999	-0.61	91	91
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.12	0.21	-9999	-0.62	48	48
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.22	-9999	-0.55	90	90
GRB7	0.004	0.084	-9999	-0.71	7	7
RET51/GFRalpha1/GDNF	-0.17	0.24	-9999	-0.61	90	90
MAPKKK cascade	-0.13	0.19	-9999	-0.61	37	37
BCAR1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.2	-9999	-0.61	45	45
lamellipodium assembly	-0.096	0.13	-9999	-0.41	38	38
RET51/GFRalpha1/GDNF/SHC	-0.17	0.24	-9999	-0.61	90	90
PIK3CA	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.12	0.2	-9999	-0.61	44	44
RET9/GFRalpha1/GDNF/Shank3	-0.12	0.2	-9999	-0.47	84	84
MAPK3	-0.11	0.22	-9999	-0.68	36	36
DOK1	0.012	0.036	-9999	-0.81	1	1
DOK6	-0.001	0.1	-9999	-0.68	11	11
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.092	0.21	-9999	-0.62	36	36
DOK5	-0.016	0.13	-9999	-0.6	25	25
GFRA1	-0.13	0.25	-9999	-0.58	128	128
MAPK8	-0.078	0.17	-9999	-0.5	39	39
HRAS/GTP	-0.15	0.22	-9999	-0.71	37	37
tube development	-0.11	0.19	-9999	-0.57	44	44
MAPK1	-0.11	0.22	-9999	-0.68	36	36
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.064	0.15	-9999	-0.53	18	18
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.006	0.08	-9999	-0.81	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.16	0.24	-9999	-0.57	97	97
SHC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.24	-9999	-0.61	90	90
RET51/GFRalpha1/GDNF/Dok5	-0.18	0.26	-9999	-0.62	105	105
PRKCA	0.011	0.044	-9999	-0.69	2	2
HRAS/GDP	-0.001	0.027	-9999	-0.63	1	1
CREB1	-0.078	0.17	-9999	-0.49	36	36
PIK3R1	0.011	0.037	-9999	-0.58	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.062	0.15	-9999	-0.52	17	17
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.25	-9999	-0.62	96	96
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.071	0.25	-9999	-0.77	56	56
DOK4	0.014	0	-9999	-10000	0	0
JNK cascade	-0.065	0.16	-9999	-0.46	39	39
RET9/GFRalpha1/GDNF/FRS2	-0.12	0.2	-9999	-0.6	48	48
SHANK3	0.014	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.58	2	2
NCK1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.062	0.15	-9999	-0.52	17	17
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.088	0.18	-9999	-0.52	38	38
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.087	0.17	-9999	-0.51	36	36
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.089	0.18	-9999	-0.57	36	36
PI3K	-0.1	0.24	-9999	-0.67	38	38
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.11	0.19	-9999	-0.57	44	44
GRB10	0.012	0.036	-9999	-0.81	1	1
activation of MAPKK activity	-0.083	0.17	-9999	-0.51	38	38
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.25	-9999	-0.61	93	93
GAB1	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.58	3	3
IRS2	0.011	0.037	-9999	-0.58	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.089	0.18	-9999	-0.57	36	36
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.25	-9999	-0.61	92	92
GRB2	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.059	0.23	-9999	-0.81	44	44
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.25	-9999	-0.61	90	90
Rac1/GTP	-0.11	0.16	-9999	-0.5	38	38
RET9/GFRalpha1/GDNF	-0.13	0.22	-9999	-0.44	155	155
GFRalpha1/GDNF	-0.15	0.25	-9999	-0.51	155	155

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.059	0.13	-9999	-0.4	15	15
PDGFB-D/PDGFRB/SLAP	-0.1	0.23	-9999	-0.61	89	89
PDGFB-D/PDGFRB/APS/CBL	-0.088	0.2	-9999	-0.52	88	88
AKT1	-0.006	0.15	-9999	-0.59	3	3
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.028	0.15	-9999	-0.42	15	15
PIK3CA	0.014	0	-9999	-10000	0	0
FGR	-0.065	0.15	-9999	-0.39	87	87
mol:Ca2+	-0.025	0.13	-9999	-0.35	11	11
MYC	0.007	0.11	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.066	0.16	-9999	-0.42	88	88
LRP1/PDGFRB/PDGFB	-0.098	0.22	-9999	-0.55	92	92
GRB10	0.012	0.036	-9999	-0.81	1	1
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	-0.025	0.13	-9999	-0.36	11	11
PTEN	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
GRB7	0.004	0.084	-9999	-0.71	7	7
PDGFB-D/PDGFRB/SHP2	-0.097	0.23	-9999	-0.61	86	86
PDGFB-D/PDGFRB/GRB10	-0.099	0.23	-9999	-0.61	87	87
cell cycle arrest	-0.1	0.23	-9999	-0.61	89	89
HRAS	0.012	0.036	-9999	-0.81	1	1
HIF1A	0.005	0.14	-9999	-0.51	3	3
GAB1	-0.025	0.14	-9999	-0.38	11	11
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.02	0.14	-9999	-0.46	2	2
PDGFB-D/PDGFRB	-0.083	0.2	-9999	-0.53	87	87
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.097	0.23	-9999	-0.61	86	86
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.06	0.13	-9999	-0.67	2	2
positive regulation of MAPKKK cascade	-0.097	0.23	-9999	-0.61	86	86
PIK3R1	0.011	0.037	-9999	-0.58	2	2
mol:IP3	-0.025	0.14	-9999	-0.36	11	11
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.1	0.24	-9999	-0.62	90	90
SHB	0.011	0.037	-9999	-0.58	2	2
BLK	-0.11	0.18	-9999	-0.43	97	97
PTPN2	0.012	0.036	-9999	-0.8	1	1
PDGFB-D/PDGFRB/SNX15	-0.097	0.23	-9999	-0.61	86	86
BCAR1	0.014	0	-9999	-10000	0	0
VAV2	-0.022	0.14	-9999	-0.42	7	7
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.097	0.23	-9999	-0.61	86	86
LCK	-0.071	0.15	-9999	-0.39	87	87
PDGFRB	-0.12	0.3	-9999	-0.8	86	86
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.065	0.15	-9999	-0.48	3	3
ABL1	-0.032	0.14	-9999	-0.35	86	86
PDGFB-D/PDGFRB/CBL	-0.024	0.13	-9999	-0.38	11	11
PTPN1	0.013	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.033	0.19	-9999	-0.79	30	30
cell proliferation	0.009	0.1	-9999	-10000	0	0
SLA	0.009	0.062	-9999	-0.81	3	3
actin cytoskeleton reorganization	-0.022	0.17	-9999	-10000	0	0
SRC	-0.063	0.15	-9999	-0.39	87	87
PI3K	-0.066	0.14	-9999	-0.67	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.092	0.2	-9999	-0.53	90	90
SH2B2	0.01	0.051	-9999	-0.81	2	2
PLCgamma1/SPHK1	-0.029	0.15	-9999	-0.43	15	15
LYN	-0.064	0.15	-9999	-0.39	87	87
LRP1	0.012	0.026	-9999	-0.58	1	1
SOS1	0.014	0	-9999	-10000	0	0
STAT5B	0.014	0	-9999	-10000	0	0
STAT5A	0.014	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.068	0.16	-9999	-0.42	12	12
SPHK1	-0.01	0.14	-9999	-0.81	15	15
EDG1	0	0.003	-9999	-10000	0	0
mol:DAG	-0.025	0.14	-9999	-0.36	11	11
PLCG1	-0.026	0.14	-9999	-0.36	11	11
NHERF/PDGFRB	-0.091	0.2	-9999	-0.53	87	87
YES1	-0.064	0.15	-9999	-0.39	87	87
cell migration	-0.09	0.2	-9999	-0.53	87	87
SHC/Grb2/SOS1	-0.068	0.16	-9999	-0.41	87	87
SLC9A3R2	0.01	0.051	-9999	-0.81	2	2
SLC9A3R1	0.009	0.052	-9999	-0.58	4	4
NHERF1-2/PDGFRB/PTEN	-0.082	0.18	-9999	-0.48	87	87
FYN	-0.064	0.15	-9999	-0.5	4	4
DOK1	-0.05	0.19	-9999	-0.47	88	88
HRAS/GTP	-0.001	0.027	-9999	-0.63	1	1
PDGFB	-0.004	0.12	-9999	-0.81	11	11
RAC1	-0.008	0.13	-9999	-10000	0	0
PRKCD	-0.048	0.19	-9999	-0.47	87	87
FER	-0.05	0.19	-9999	-0.48	87	87
MAPKKK cascade	-0.067	0.15	-9999	-0.41	87	87
RASA1	-0.05	0.19	-9999	-0.47	87	87
NCK1	0.014	0	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	-0.066	0.17	-9999	-0.43	88	88
PDGFB-D/PDGFRB/SHB	-0.099	0.23	-9999	-0.6	88	88
chemotaxis	-0.031	0.14	-9999	-0.34	86	86
STAT1-3-5/STAT1-3-5	-0.089	0.18	-9999	-0.83	6	6
Bovine Papilomavirus E5/PDGFRB	-0.093	0.23	-9999	-0.62	86	86
PTPRJ	0.014	0	-9999	-10000	0	0

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.088	0.22	-10000	0	-0.55	59	59
TBX21	-0.14	0.45	-10000	0	-1.2	59	59
B2M	0.012	0.009	-10000	0	-10000	0	0
TYK2	0.016	0.042	-10000	0	-0.83	1	1
IL12RB1	-0.044	0.22	-10000	0	-0.82	39	39
GADD45B	-0.056	0.29	-10000	0	-0.8	30	30
IL12RB2	-0.16	0.34	-10000	0	-0.79	114	114
GADD45G	-0.066	0.31	-10000	0	-0.87	32	32
natural killer cell activation	0.006	0.024	-10000	0	-10000	0	0
RELB	0.004	0.088	-10000	0	-0.81	6	6
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.005	0.11	-10000	0	-0.58	19	19
IL2RA	-0.061	0.24	-10000	0	-0.81	47	47
IFNG	-0.16	0.33	-10000	0	-0.81	106	106
STAT3 (dimer)	-0.077	0.32	-10000	0	-0.79	56	56
HLA-DRB5	-0.012	0.13	-10000	0	-0.71	18	18
FASLG	-0.14	0.46	-10000	0	-1.2	64	64
NF kappa B2 p52/RelB	-0.2	0.35	-10000	0	-0.95	72	72
CD4	0.01	0.045	-10000	0	-0.7	2	2
SOCS1	-0.039	0.2	-10000	0	-0.81	33	33
EntrezGene:6955	-0.004	0.015	-10000	0	-10000	0	0
CD3D	-0.011	0.13	-10000	0	-0.72	16	16
CD3E	-0.008	0.12	-10000	0	-0.75	13	13
CD3G	-0.028	0.16	-10000	0	-0.67	30	30
IL12Rbeta2/JAK2	-0.11	0.27	-10000	0	-0.6	115	115
CCL3	-0.13	0.43	-10000	0	-1.1	58	58
CCL4	-0.12	0.42	-10000	0	-1.1	58	58
HLA-A	0.003	0.084	-10000	0	-0.77	6	6
IL18/IL18R	0.025	0.13	-10000	0	-0.51	19	19
NOS2	-0.14	0.42	-10000	0	-1	58	58
IL12/IL12R/TYK2/JAK2/SPHK2	-0.069	0.2	-10000	0	-0.52	52	52
IL1R1	-0.11	0.4	-10000	0	-1	55	55
IL4	-0.005	0.024	-10000	0	-10000	0	0
JAK2	0.016	0.034	-10000	0	-0.6	1	1
EntrezGene:6957	-0.004	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.093	0.33	-10000	0	-0.85	62	62
RAB7A	-0.032	0.27	-10000	0	-0.72	20	20
lysosomal transport	-0.028	0.26	-10000	0	-0.68	21	21
FOS	-0.16	0.48	-10000	0	-1.2	77	77
STAT4 (dimer)	-0.079	0.35	-10000	0	-0.86	54	54
STAT5A (dimer)	-0.26	0.41	-10000	0	-1	93	93
GZMA	-0.15	0.47	-10000	0	-1.2	60	60
GZMB	-0.16	0.47	-10000	0	-1.1	78	78
HLX	0.007	0.072	-10000	0	-0.81	4	4
LCK	-0.14	0.45	-10000	0	-1.1	66	66
TCR/CD3/MHC II/CD4	-0.032	0.19	-10000	0	-0.58	36	36
IL2/IL2R	-0.067	0.19	-10000	0	-0.56	60	60
MAPK14	-0.056	0.31	-10000	0	-0.81	36	36
CCR5	-0.078	0.34	-10000	0	-1.1	27	27
IL1B	-0.063	0.24	-10000	0	-0.79	52	52
STAT6	-0.01	0.12	-10000	0	-10000	0	0
STAT4	-0.008	0.13	-10000	0	-0.79	14	14
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.033	0.19	-10000	0	-0.79	30	30
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.014	0	-10000	0	-10000	0	0
IL12B	-0.05	0.23	-10000	0	-0.81	44	44
CD8A	-0.043	0.2	-10000	0	-0.73	39	39
CD8B	-0.066	0.23	-10000	0	-0.73	55	55
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.087	0.22	0.54	59	-10000	0	59
IL2RB	0.001	0.098	-10000	0	-0.78	8	8
proteasomal ubiquitin-dependent protein catabolic process	-0.068	0.32	-10000	0	-0.78	53	53
IL2RG	-0.012	0.14	-10000	0	-0.78	17	17
IL12	-0.044	0.21	-10000	0	-0.58	63	63
STAT5A	0.014	0	-10000	0	-10000	0	0
CD247	-0.021	0.16	-10000	0	-0.79	21	21
IL2	0.003	0.036	-10000	0	-0.81	1	1
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.008	0.13	-10000	0	-0.64	20	20
IL12/IL12R/TYK2/JAK2	-0.15	0.49	-10000	0	-1.2	71	71
MAP2K3	-0.056	0.31	-10000	0	-0.79	37	37
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.067	0.32	-10000	0	-0.81	40	40
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.045	-10000	0	-0.58	3	3
IL18RAP	-0.009	0.14	-10000	0	-0.73	18	18
IL12Rbeta1/TYK2	-0.024	0.18	-10000	0	-0.64	40	40
EOMES	-0.078	0.26	-10000	0	-0.67	73	73
STAT1 (dimer)	-0.13	0.37	-10000	0	-0.87	73	73
T cell proliferation	-0.028	0.26	0.48	1	-0.65	34	35
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.014	0.046	-10000	0	-0.71	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.22	-10000	0	-0.73	35	35
ATF2	-0.043	0.29	-10000	0	-0.76	32	32

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.017	0.085	-9999	-0.47	16	16
RGS9BP	0.002	0.081	-9999	-0.58	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0.05	-9999	-0.81	2	2
mol:Na +	-0.092	0.2	-9999	-0.54	88	88
mol:ADP	-0.053	0.2	-9999	-0.62	54	54
GNAT2	0.012	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.018	0.089	-9999	-0.53	10	10
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.07	0.25	-9999	-0.81	52	52
CNGB3	-0.13	0.31	-9999	-0.81	87	87
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.17	0.28	-9999	-0.55	172	172
Cone PDE6	-0.016	0.076	-9999	-0.46	10	10
Cone Metarhodopsin II	-0.053	0.15	-9999	-0.51	54	54
Na + (4 Units)	-0.18	0.28	-9999	-0.55	172	172
GNAT2/GDP	-0.015	0.076	-9999	-0.46	10	10
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.01	0.006	-9999	-10000	0	0
Cone Transducin	-0.018	0.089	-9999	-0.49	16	16
SLC24A2	-0.16	0.33	-9999	-0.81	106	106
GNB3/GNGT2	-0.022	0.11	-9999	-0.58	20	20
GNB3	-0.014	0.15	-9999	-0.78	18	18
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.007	0.036	-9999	-0.81	1	1
ARR3	0.002	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.092	0.2	-9999	-0.55	88	88
mol:Pi	-0.018	0.089	-9999	-0.53	10	10
Cone CNG Channel	-0.077	0.17	-9999	-0.45	88	88
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.16	0.33	-9999	-0.81	106	106
RGS9	-0.005	0.12	-9999	-0.77	12	12
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	0.011	0.037	-9999	-0.58	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.005	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.013	0.063	-10000	0	-10000	0	0
SMARCC2	0.015	0.006	-10000	0	-10000	0	0
SMARCC1	0.015	0.006	-10000	0	-10000	0	0
TBX21	-0.093	0.23	-10000	0	-0.85	34	34
SUMO2	0.014	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	-0.024	0.19	-10000	0	-0.78	30	30
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	0.01	0.051	-10000	0	-0.65	3	3
GR alpha/HSP90/FKBP51/HSP90	0.095	0.098	0.37	9	-0.55	1	10
PRL	-0.097	0.17	-10000	0	-0.74	7	7
cortisol/GR alpha (dimer)/TIF2	0.17	0.24	0.58	61	-0.46	1	62
RELA	-0.003	0.092	-10000	0	-10000	0	0
FGG	0.1	0.28	0.56	23	-0.65	40	63
GR beta/TIF2	0.062	0.15	0.37	16	-0.39	15	31
IFNG	-0.36	0.33	-10000	0	-0.89	118	118
apoptosis	0.024	0.18	0.49	14	-0.63	5	19
CREB1	0.016	0.018	-10000	0	-10000	0	0
histone acetylation	0.005	0.12	0.46	4	-0.46	5	9
BGLAP	-0.048	0.14	-10000	0	-0.76	8	8
GR/PKAc	0.095	0.088	0.38	5	-10000	0	5
NF kappa B1 p50/RelA	-0.014	0.16	-10000	0	-0.48	8	8
SMARCD1	0.015	0.006	-10000	0	-10000	0	0
MDM2	0.08	0.083	0.31	16	-10000	0	16
GATA3	-0.012	0.15	-10000	0	-0.77	20	20
AKT1	0	0.001	-10000	0	-10000	0	0
CSF2	-0.3	0.28	-10000	0	-0.56	256	256
GSK3B	0.014	0.008	-10000	0	-10000	0	0
NR1I3	0.053	0.17	0.51	9	-0.67	5	14
CSN2	0.12	0.15	0.46	14	-0.53	2	16
BRG1/BAF155/BAF170/BAF60A	0.037	0.025	-10000	0	-10000	0	0
NFATC1	0.015	0.003	-10000	0	-10000	0	0
POU2F1	0.015	0.016	-10000	0	-10000	0	0
CDKN1A	0.031	0.037	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	-10000	0	-10000	0	0
SFN	0.008	0.062	-10000	0	-0.69	4	4
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.098	0.39	4	-0.5	1	5
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.027	0.24	0.49	9	-0.85	25	34
JUN	-0.21	0.17	-10000	0	-0.64	37	37
IL4	-0.066	0.12	-10000	0	-0.57	3	3
CDK5R1	0.011	0.051	-10000	0	-0.81	2	2
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.15	0.31	-10000	0	-0.64	80	80
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.099	0.093	0.38	5	-0.5	1	6
cortisol/GR alpha (monomer)	0.24	0.27	0.68	80	-10000	0	80
NCOA2	-0.034	0.16	-10000	0	-0.58	42	42
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.2	-10000	0	-0.64	67	67
AP-1/NFAT1-c-4	-0.4	0.26	-10000	0	-0.82	98	98
AFP	-0.16	0.2	-10000	0	-0.83	30	30
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.11	0.16	0.5	13	-10000	0	13
TP53	0.033	0.052	-10000	0	-0.56	4	4
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.39	0.38	-10000	0	-0.94	147	147
KRT14	-0.22	0.37	-10000	0	-1.1	70	70
TBP	0.021	0.023	-10000	0	-10000	0	0
CREBBP	0.073	0.084	0.35	6	-10000	0	6
HDAC1	0.012	0.01	-10000	0	-10000	0	0
HDAC2	0.043	0.031	-10000	0	-10000	0	0
AP-1	-0.41	0.27	-10000	0	-0.83	98	98
MAPK14	0.014	0.008	-10000	0	-10000	0	0
MAPK10	-0.019	0.14	-10000	0	-0.61	28	28
MAPK11	0.014	0.008	-10000	0	-10000	0	0
KRT5	-0.26	0.23	-10000	0	-0.74	50	50
interleukin-1 receptor activity	0.03	0.031	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	-0.024	0.19	-10000	0	-0.78	30	30
CGA	-0.061	0.13	-10000	0	-0.7	7	7
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.25	0.2	0.42	263	-10000	0	263
MAPK3	0.014	0.008	-10000	0	-10000	0	0
MAPK1	0.014	0.008	-10000	0	-10000	0	0
ICAM1	-0.13	0.24	-10000	0	-0.7	51	51
NFKB1	-0.003	0.092	-10000	0	-10000	0	0
MAPK8	-0.16	0.16	-10000	0	-0.58	36	36
MAPK9	0.014	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.017	0.18	0.5	13	-0.66	5	18
BAX	0.031	0.037	-10000	0	-10000	0	0
POMC	-0.17	0.32	-10000	0	-0.9	60	60
EP300	0.073	0.086	0.36	6	-10000	0	6
cortisol/GR alpha (dimer)/p53	0.22	0.22	0.6	68	-0.53	1	69
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.063	0.28	3	-10000	0	3
SGK1	0.12	0.13	-10000	0	-1.2	2	2
IL13	-0.21	0.19	-10000	0	-0.83	23	23
IL6	-0.18	0.35	-10000	0	-1	65	65
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.19	0.16	-10000	0	-0.76	12	12
IL2	-0.26	0.2	-10000	0	-0.67	50	50
CDK5	0.014	0.005	-10000	0	-10000	0	0
PRKACB	0.012	0.026	-10000	0	-0.58	1	1
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.21	0.34	-10000	0	-0.76	118	118
CDK5R1/CDK5	0.003	0.041	-10000	0	-0.62	2	2
NF kappa B1 p50/RelA/PKAc	0.014	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.2	0.56	64	-10000	0	64
SMARCA4	0.015	0.006	-10000	0	-10000	0	0
chromatin remodeling	0.15	0.13	0.41	37	-10000	0	37
NF kappa B1 p50/RelA/Cbp	0.073	0.16	0.42	18	-10000	0	18
JUN (dimer)	-0.21	0.17	-10000	0	-0.64	37	37
YWHAH	0.014	0	-10000	0	-10000	0	0
VIPR1	-0.082	0.21	-10000	0	-0.88	24	24
NR3C1	0.14	0.16	0.5	40	-10000	0	40
NR4A1	-0.027	0.13	-10000	0	-0.55	15	15
TIF2/SUV420H1	-0.034	0.11	-10000	0	-0.42	42	42
MAPKKK cascade	0.024	0.18	0.49	14	-0.63	5	19
cortisol/GR alpha (dimer)/Src-1	0.22	0.22	0.59	73	-10000	0	73
PBX1	-0.09	0.23	-10000	0	-0.58	92	92
POU1F1	0.003	0.017	-10000	0	-10000	0	0
SELE	-0.22	0.4	-10000	0	-1.1	80	80
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.13	0.42	36	-10000	0	36
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.2	0.56	64	-10000	0	64
mol:cortisol	0.13	0.16	0.41	78	-10000	0	78
MMP1	-0.64	0.23	-10000	0	-0.71	460	460

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.064	0.16	-10000	0	-0.56	35	35
FYN	-0.032	0.23	-10000	0	-0.74	35	35
LAT/GRAP2/SLP76	-0.05	0.19	-10000	0	-0.62	37	37
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.008	0.16	-10000	0	-0.48	34	34
B2M	0.013	0.005	-10000	0	-10000	0	0
IKBKG	-0.019	0.042	-10000	0	-0.18	3	3
MAP3K8	0.01	0.045	-10000	0	-0.58	3	3
mol:Ca2+	-0.036	0.04	-10000	0	-0.11	38	38
integrin-mediated signaling pathway	-0.002	0.027	-10000	0	-0.35	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.03	0.23	-10000	0	-0.69	40	40
TRPV6	-0.27	0.29	-10000	0	-0.59	238	238
CD28	-0.013	0.14	-10000	0	-0.78	17	17
SHC1	-0.036	0.23	-10000	0	-0.68	44	44
receptor internalization	-0.037	0.24	-10000	0	-0.69	46	46
PRF1	-0.053	0.28	-10000	0	-0.89	46	46
KRAS	0.01	0.051	-10000	0	-0.81	2	2
GRB2	0.014	0	-10000	0	-10000	0	0
COT/AKT1	0.002	0.13	-10000	0	-0.38	33	33
LAT	-0.044	0.25	-10000	0	-0.72	46	46
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.009	0.13	-10000	0	-0.72	16	16
CD3E	-0.005	0.12	-10000	0	-0.75	13	13
CD3G	-0.026	0.16	-10000	0	-0.67	30	30
RASGRP2	0.007	0.023	-10000	0	-0.12	7	7
RASGRP1	-0.005	0.17	-10000	0	-0.48	37	37
HLA-A	0.005	0.084	-10000	0	-0.76	6	6
RASSF5	0.01	0.045	-10000	0	-0.58	3	3
RAP1A/GTP/RAPL	-0.002	0.027	-10000	0	-0.35	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.056	-10000	0	-0.13	19	19
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.036	0.073	-10000	0	-0.29	11	11
PRKCA	-0.011	0.094	-10000	0	-0.31	23	23
GRAP2	-0.002	0.1	-10000	0	-0.67	12	12
mol:IP3	0.037	0.19	0.23	178	-0.48	27	205
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.035	0.22	-10000	0	-0.62	49	49
ORAI1	0.15	0.16	0.32	238	-10000	0	238
CSK	-0.04	0.23	-10000	0	-0.71	42	42
B7 family/CD28	-0.16	0.27	-10000	0	-0.8	55	55
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.055	0.27	-10000	0	-0.81	44	44
PTPN6	-0.043	0.23	-10000	0	-0.72	41	41
VAV1	-0.04	0.24	-10000	0	-0.74	39	39
Monovalent TCR/CD3	-0.02	0.17	-10000	0	-0.59	33	33
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.04	0.24	-10000	0	-0.73	42	42
PAG1	-0.041	0.23	-10000	0	-0.7	44	44
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.056	0.26	-10000	0	-0.79	45	45
CD80	-0.19	0.35	-10000	0	-0.81	128	128
CD86	0.012	0.036	-10000	0	-0.81	1	1
PDK1/CARD11/BCL10/MALT1	-0.044	0.09	-10000	0	-0.33	20	20
HRAS	0.012	0.036	-10000	0	-0.81	1	1
GO:0035030	-0.086	0.24	-10000	0	-0.64	55	55
CD8A	-0.041	0.2	-10000	0	-0.72	39	39
CD8B	-0.064	0.23	-10000	0	-0.73	55	55
PTPRC	-0.003	0.11	-10000	0	-0.7	12	12
PDK1/PKC theta	-0.01	0.19	-10000	0	-0.6	34	34
CSK/PAG1	-0.035	0.22	-10000	0	-0.73	36	36
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.012	0.065	-10000	0	-0.58	6	6
GRAP2/SLP76	-0.061	0.21	-10000	0	-0.71	37	37
STIM1	0.075	0.079	-10000	0	-10000	0	0
RAS family/GTP	0.025	0.072	-10000	0	-0.19	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.042	0.26	-10000	0	-0.75	46	46
mol:DAG	-0.013	0.14	-10000	0	-0.43	29	29
RAP1A/GDP	0.013	0.024	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.018	0.16	-10000	0	-0.78	21	21
cytotoxic T cell degranulation	-0.049	0.27	-10000	0	-0.83	47	47
RAP1A/GTP	-0.002	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.018	0.19	-10000	0	-0.55	40	40
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.023	0.23	0.26	129	-0.64	29	158
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.024	0.17	-10000	0	-0.77	25	25
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.045	0.19	-10000	0	-0.62	35	35
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.014	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.075	0.27	-10000	0	-0.71	69	69
CARD11	-0.037	0.2	-10000	0	-0.79	33	33
PRKCB	-0.013	0.1	-10000	0	-0.36	22	22
PRKCE	-0.01	0.093	-10000	0	-0.3	22	22
PRKCQ	-0.023	0.22	-10000	0	-0.66	39	39
LCP2	0.009	0.062	-10000	0	-0.81	3	3
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.002	0.14	-10000	0	-0.4	33	33
IKK complex	0.033	0.053	-10000	0	-0.13	6	6
RAS family/GDP	-0.003	0.009	-10000	0	-0.085	3	3
MAP3K14	0.012	0.1	-10000	0	-0.31	18	18
PDPK1	-0.004	0.15	-10000	0	-0.45	34	34
TCR/CD3/MHC I/CD8/Fyn	-0.048	0.26	-10000	0	-0.8	45	45

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.16	0.25	-10000	0	-0.54	152	152
cell-cell adhesion	0.13	0.18	0.69	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	-0.14	0.21	-10000	0	-0.47	137	137
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.01	0.057	-10000	0	-0.35	14	14
Ephrin B1/EPHB1	-0.028	0.11	-10000	0	-0.48	30	30
HRAS/GDP	-0.058	0.11	-10000	0	-0.61	4	4
Ephrin B/EPHB1/GRB7	-0.046	0.13	-10000	0	-0.48	26	26
Endophilin/SYNJ1	-0.1	0.21	-10000	0	-0.43	137	137
KRAS	0.01	0.051	-10000	0	-0.81	2	2
Ephrin B/EPHB1/Src	-0.041	0.12	-10000	0	-0.48	22	22
endothelial cell migration	-0.002	0.022	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
GRB7	0.004	0.084	-10000	0	-0.71	7	7
PAK1	-0.12	0.23	-10000	0	-0.7	18	18
HRAS	0.012	0.036	-10000	0	-0.81	1	1
RRAS	-0.1	0.22	-10000	0	-0.44	137	137
DNM1	-0.045	0.21	-10000	0	-0.81	37	37
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.003	0.13	-10000	0	-0.46	22	22
lamellipodium assembly	-0.13	0.18	-10000	0	-0.69	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.011	0.091	-10000	0	-0.46	3	3
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
EPHB2	-0.2	0.36	-10000	0	-0.81	138	138
EPHB3	-0.002	0.096	-10000	0	-0.58	14	14
EPHB1	-0.029	0.18	-10000	0	-0.73	30	30
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.055	0.11	-10000	0	-0.52	6	6
Ephrin B/EPHB2	-0.14	0.21	-10000	0	-0.47	137	137
Ephrin B/EPHB3	-0.026	0.086	-10000	0	-0.52	2	2
JNK cascade	-0.11	0.23	-10000	0	-0.45	155	155
Ephrin B/EPHB1	-0.042	0.12	-10000	0	-0.49	22	22
RAP1/GDP	-0.045	0.092	-10000	0	-0.53	3	3
EFNB2	0.012	0.026	-10000	0	-0.58	1	1
EFNB3	-0.023	0.14	-10000	0	-0.58	32	32
EFNB1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.16	0.23	-10000	0	-0.5	155	155
RAP1B	0.012	0.036	-10000	0	-0.81	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.13	0.18	-10000	0	-0.75	8	8
Rap1/GTP	-0.13	0.18	-10000	0	-0.75	7	7
axon guidance	-0.16	0.25	-10000	0	-0.54	152	152
MAPK3	0.027	0.082	-10000	0	-0.41	3	3
MAPK1	0.027	0.082	-10000	0	-0.41	3	3
Rac1/GDP	-0.016	0.12	-10000	0	-0.56	3	3
actin cytoskeleton reorganization	-0.1	0.14	-10000	0	-0.54	8	8
CDC42/GDP	-0.016	0.12	-10000	0	-0.56	3	3
PI3K	-0.002	0.022	-10000	0	-10000	0	0
EFNA5	-0.014	0.12	-10000	0	-0.58	24	24
Ephrin B2/EPHB4	-0.001	0.016	-10000	0	-0.35	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.056	0.14	-10000	0	-0.52	5	5
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.13	0.18	-10000	0	-0.72	8	8
PTK2	0.032	0.047	-10000	0	-10000	0	0
MAP4K4	-0.11	0.23	-10000	0	-0.46	155	155
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.038	0.17	-10000	0	-0.58	45	45
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.063	0.18	-10000	0	-0.51	14	14
MAP2K1	0.019	0.086	-10000	0	-0.43	3	3
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.15	0.23	-10000	0	-0.49	155	155
cell migration	0.023	0.098	-10000	0	-0.49	3	3
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	-0.1	0.22	-10000	0	-0.44	137	137
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.28	0.25	-10000	0	-0.67	120	120
HRAS/GTP	-0.14	0.19	-10000	0	-0.77	9	9
Ephrin B1/EPHB1-2	-0.16	0.23	-10000	0	-0.5	155	155
cell adhesion mediated by integrin	0.014	0.08	0.44	2	-10000	0	2
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.15	0.21	-10000	0	-0.85	8	8
RAC1-CDC42/GTP	-0.13	0.18	-10000	0	-0.73	9	9
RASA1	0.011	0.037	-10000	0	-0.58	2	2
RAC1-CDC42/GDP	-0.045	0.091	-10000	0	-0.53	3	3
ruffle organization	-0.085	0.21	-10000	0	-0.75	7	7
NCK1	0.014	0	-10000	0	-10000	0	0
receptor internalization	-0.12	0.25	-10000	0	-0.8	23	23
Ephrin B/EPHB2/KALRN	-0.16	0.22	-10000	0	-0.48	143	143
ROCK1	0.018	0.055	-10000	0	-10000	0	0
RAS family/GDP	-0.1	0.14	-10000	0	-0.54	8	8
Rac1/GTP	-0.14	0.19	-10000	0	-0.77	8	8
Ephrin B/EPHB1/Src/Paxillin	0.005	0.097	-10000	0	-0.51	3	3

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0.036	-10000	0	-0.81	1	1
RAS family/GTP/Tiam1	-0.085	0.11	-10000	0	-0.48	5	5
NT3 (dimer)/TRKC	-0.22	0.27	-10000	0	-0.5	228	228
NT3 (dimer)/TRKB	-0.22	0.26	-10000	0	-0.66	100	100
SHC/Grb2/SOS1/GAB1/PI3K	0.039	0.017	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.038	0.18	-10000	0	-0.69	38	38
PIK3CA	0.014	0	-10000	0	-10000	0	0
DYNLT1	0.014	0	-10000	0	-10000	0	0
NTRK1	-0.059	0.23	-10000	0	-0.81	46	46
NTRK2	-0.16	0.29	-10000	0	-0.62	140	140
NTRK3	-0.14	0.26	-10000	0	-0.58	128	128
NT-4/5 (dimer)/TRKB	-0.13	0.21	-10000	0	-0.59	48	48
neuron apoptosis	0.11	0.13	0.48	23	-10000	0	23
SHC 2-3/Grb2	-0.12	0.14	-10000	0	-0.52	23	23
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.11	0.13	0.22	1	-0.41	55	56
SHC3	-0.11	0.14	-10000	0	-0.44	51	51
STAT3 (dimer)	0.013	0.054	-10000	0	-0.34	3	3
NT3 (dimer)/TRKA	-0.17	0.23	-10000	0	-0.62	67	67
RIN/GDP	-0.047	0.099	-10000	0	-0.28	7	7
GIPC1	0.014	0	-10000	0	-10000	0	0
KRAS	0.01	0.051	-10000	0	-0.81	2	2
DNAJA3	-0.08	0.13	0.25	2	-0.48	8	10
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.014	0.12	-10000	0	-0.73	13	13
MAGED1	0.008	0.062	-10000	0	-0.69	4	4
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.009	0.057	-10000	0	-0.73	3	3
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.16	0.26	-10000	0	-0.57	138	138
TRKA/NEDD4-2	-0.055	0.18	-10000	0	-0.62	46	46
ELMO1	0.011	0.044	-10000	0	-0.69	2	2
RhoG/GTP/ELMO1/DOCK1	-0.003	0.036	-10000	0	-0.4	4	4
NGF	-0.14	0.32	-10000	0	-0.79	98	98
HRAS	0.012	0.036	-10000	0	-0.81	1	1
DOCK1	0.011	0.037	-10000	0	-0.58	2	2
GAB2	0.01	0.045	-10000	0	-0.58	3	3
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.007	0.072	-10000	0	-0.81	4	4
DNM1	-0.045	0.21	-10000	0	-0.81	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.079	0.12	0.24	2	-0.47	11	13
mol:GDP	-0.07	0.14	-10000	0	-0.41	13	13
NGF (dimer)	-0.14	0.31	-10000	0	-0.79	98	98
RhoG/GDP	-0.002	0.033	-10000	0	-0.53	2	2
RIT1/GDP	-0.041	0.1	-10000	0	-0.28	5	5
TIAM1	0.007	0.063	-10000	0	-0.58	6	6
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
BDNF (dimer)/TRKB	-0.13	0.21	-10000	0	-0.59	46	46
KIDINS220/CRKL/C3G	-0.001	0.027	-10000	0	-0.62	1	1
SHC/RasGAP	-0.002	0.026	-10000	0	-0.42	2	2
FRS2 family/SHP2	-0.004	0.047	-10000	0	-0.53	4	4
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.16	0.27	-10000	0	-0.58	154	154
RAP1/GDP	-0.054	0.066	-10000	0	-0.35	1	1
KIDINS220/CRKL	0.012	0.036	-10000	0	-0.81	1	1
BDNF (dimer)	-0.038	0.18	-10000	0	-0.68	38	38
ubiquitin-dependent protein catabolic process	-0.14	0.25	-10000	0	-0.56	129	129
Schwann cell development	-0.049	0.036	-10000	0	-10000	0	0
EHD4	0.014	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.004	0.042	-10000	0	-0.48	4	4
FRS2 family/SHP2/CRK family/C3G/GAB2	0.039	0.03	-10000	0	-10000	0	0
RAP1B	0.012	0.036	-10000	0	-0.81	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.25	0.26	-10000	0	-0.62	143	143
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.045	0.07	-10000	0	-0.56	1	1
STAT3	0.013	0.054	-10000	0	-0.34	3	3
axon guidance	-0.24	0.25	-10000	0	-0.58	143	143
MAPK3	-0.12	0.25	-10000	0	-0.52	138	138
MAPK1	-0.12	0.25	-10000	0	-0.52	138	138
CDC42/GDP	-0.041	0.1	-10000	0	-0.28	5	5
NTF3	-0.16	0.27	-10000	0	-0.58	154	154
NTF4	0.009	0.057	-10000	0	-0.73	3	3
NGF (dimer)/TRKA/FAIM	-0.14	0.25	-10000	0	-0.56	129	129
PI3K	-0.002	0.026	-10000	0	-0.42	2	2
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.014	0	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
RASGRF1	-0.17	0.23	0.25	2	-0.55	108	110
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.19	0.26	-10000	0	-0.45	233	233
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.086	-10000	0	-10000	0	0
Rac1/GDP	-0.041	0.1	-10000	0	-0.28	5	5
NGF (dimer)/TRKA/GRIT	-0.15	0.25	-10000	0	-0.56	137	137
neuron projection morphogenesis	-0.043	0.13	-10000	0	-0.5	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.14	0.25	-10000	0	-0.56	129	129
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.023	0.16	-10000	0	-0.71	26	26
NGF (dimer)/TRKA/GIPC/GAIP	-0.062	0.16	-10000	0	-0.52	16	16
RAS family/GTP/PI3K	0.03	0.028	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.003	0.039	-10000	0	-0.45	4	4
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.026	-10000	0	-0.58	1	1
MAPKKK cascade	-0.084	0.14	-10000	0	-0.49	18	18
RASA1	0.011	0.037	-10000	0	-0.58	2	2
TRKA/c-Abl	-0.055	0.18	-10000	0	-0.62	46	46
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.12	0.19	-10000	0	-0.54	46	46
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.12	0.21	-10000	0	-0.48	129	129
MATK	-0.005	0.12	-10000	0	-0.77	12	12
NEDD4L	0.014	0	-10000	0	-10000	0	0
RAS family/GDP	-0.052	0.063	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.086	0.14	0.26	2	-0.38	33	35
Rac1/GTP	-0.12	0.13	-10000	0	-0.37	56	56
FRS2 family/SHP2/CRK family	-0.004	0.044	-10000	0	-0.45	5	5

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.02	0.016	-9999	-0.35	1	1
ADCY5	-0.072	0.17	-9999	-0.37	124	124
ADCY6	0.013	0.054	-9999	-0.36	11	11
ADCY7	0.02	0.016	-9999	-0.35	1	1
ADCY1	-0.005	0.12	-9999	-0.54	24	24
ADCY2	-0.11	0.18	-9999	-0.36	176	176
ADCY3	0.02	0.016	-9999	-0.35	1	1
ADCY8	0	0.085	-9999	-0.53	13	13
PRKCE	0.011	0.019	-9999	-0.42	1	1
ADCY9	0.019	0.028	-9999	-0.36	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.046	0.096	-9999	-0.37	8	8

×

Thromboxane A2 receptor signaling

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
TGM2	-0.033	0.18	-10000	0	-0.81	28	28
GNB1/GNG2	-0.053	0.076	-10000	0	-0.21	36	36
AKT1	0.001	0.11	-10000	0	-0.26	1	1
EGF	-0.1	0.24	-10000	0	-0.58	101	101
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.014	0.12	-10000	0	-0.48	14	14
mol:Ca2+	-0.024	0.16	-10000	0	-0.3	87	87
LYN	0.014	0.12	-10000	0	-0.49	14	14
RhoA/GTP	-0.032	0.049	-10000	0	-0.16	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.026	0.18	-10000	0	-0.34	92	92
GNG2	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.007	0.084	-10000	0	-0.52	5	5
G beta5/gamma2	-0.068	0.1	-10000	0	-0.29	35	35
PRKCH	-0.031	0.18	-10000	0	-0.38	37	37
DNM1	-0.045	0.21	-10000	0	-0.81	37	37
TXA2/TP beta/beta Arrestin3	-0.023	0.067	-10000	0	-0.32	6	6
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.001	0.095	-10000	0	-0.7	9	9
G12 family/GTP	-0.078	0.12	-10000	0	-0.32	42	42
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.036	-10000	0	-0.81	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.12	0.36	27	-10000	0	27
mol:NADP	0.002	0.094	-10000	0	-0.81	7	7
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.024	0.15	-10000	0	-0.64	30	30
mol:IP3	-0.038	0.19	-10000	0	-0.37	91	91
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.064	0.25	-10000	0	-0.5	92	92
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.043	0.18	-10000	0	-0.47	40	40
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.011	0.12	-10000	0	-0.5	15	15
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.02	0.16	-10000	0	-0.81	21	21
PRKCB1	-0.038	0.19	-10000	0	-0.37	91	91
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.002	0.094	-10000	0	-0.81	7	7
TXA2/TXA2-R family	-0.064	0.25	-10000	0	-0.51	99	99
LCK	0.005	0.13	-10000	0	-0.46	20	20
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.04	0.13	-10000	0	-0.51	34	34
TXA2-R family/G12 family/GDP/G beta/gamma	0.021	0.046	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.039	0.13	-10000	0	-0.5	34	34
MAPK14	-0.004	0.13	-10000	0	-0.25	11	11
TGM2/GTP	-0.049	0.22	-10000	0	-0.48	41	41
MAPK11	-0.004	0.13	-10000	0	-0.25	10	10
ARHGEF1	-0.005	0.099	-10000	0	-0.22	2	2
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.037	0.2	-10000	0	-0.38	94	94
RAB11/GDP	0.013	0.002	-10000	0	-10000	0	0
ICAM1	-0.024	0.16	-10000	0	-0.3	96	96
cAMP biosynthetic process	-0.038	0.18	-10000	0	-0.38	42	42
Gq family/GTP/EBP50	-0.006	0.094	-10000	0	-0.39	8	8
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.015	0.12	-10000	0	-0.49	13	13
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.004	0.11	-10000	0	-0.34	19	19
VCAM1	-0.032	0.17	-10000	0	-0.33	107	107
TP beta/Gq family/GDP/G beta5/gamma2	0.007	0.084	-10000	0	-0.52	5	5
platelet activation	-0.008	0.17	-10000	0	-0.32	33	33
PGI2/IP	-0.025	0.12	-10000	0	-0.63	21	21
PRKACA	0.004	0.082	-10000	0	-0.34	24	24
Gq family/GDP/G beta5/gamma2	0.01	0.075	-10000	0	-0.42	5	5
TXA2/TP beta/beta Arrestin2	-0.029	0.092	-10000	0	-0.36	36	36
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.018	0.16	-10000	0	-0.57	34	34
mol:DAG	-0.045	0.21	-10000	0	-0.42	91	91
EGFR	-0.015	0.15	-10000	0	-0.76	19	19
TXA2/TP alpha	-0.058	0.24	-10000	0	-0.52	47	47
Gq family/GTP	-0.033	0.089	-10000	0	-0.24	76	76
YES1	0.015	0.12	-10000	0	-0.49	13	13
GNAI2/GTP	-0.036	0.12	-10000	0	-0.48	25	25
PGD2/DP	-0.009	0.071	-10000	0	-0.54	9	9
SLC9A3R1	0.009	0.052	-10000	0	-0.58	4	4
FYN	0.014	0.12	-10000	0	-0.5	14	14
mol:NO	0.002	0.094	-10000	0	-0.81	7	7
GNA15	0.011	0.037	-10000	0	-0.58	2	2
PGK/cGMP	-0.031	0.11	-10000	0	-0.43	37	37
RhoA/GDP	0.013	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.06	0.18	-10000	0	-0.78	20	20
NOS3	0.002	0.095	-10000	0	-0.81	7	7
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.031	0.18	-10000	0	-0.38	37	37
PRKCB	-0.035	0.18	-10000	0	-0.36	85	85
PRKCE	-0.031	0.18	-10000	0	-0.35	81	81
PRKCD	-0.035	0.19	-10000	0	-0.38	86	86
PRKCG	-0.059	0.22	-10000	0	-0.43	101	101
muscle contraction	-0.053	0.24	-10000	0	-0.47	99	99
PRKCZ	-0.025	0.18	-10000	0	-0.37	33	33
ARR3	0.002	0.005	-10000	0	-10000	0	0
TXA2/TP beta	-0.04	0.14	-10000	0	-0.5	35	35
PRKCQ	-0.035	0.18	-10000	0	-0.36	86	86
MAPKKK cascade	-0.05	0.22	-10000	0	-0.44	93	93
SELE	-0.038	0.18	-10000	0	-0.39	86	86
TP beta/GNAI2/GDP/G beta/gamma	-0.039	0.13	-10000	0	-0.66	13	13
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.072	0.21	-10000	0	-0.58	75	75
chemotaxis	-0.078	0.28	-10000	0	-0.6	98	98
GNA12	0.007	0.072	-10000	0	-0.81	4	4
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.009	0.052	-10000	0	-0.58	4	4
Rac1/GTP	0.006	0.006	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.003	0.017	-10000	0	-10000	0	0
AES	0.003	0.014	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.007	0.065	-10000	0	-0.56	7	7
SMAD4	0.012	0.026	-10000	0	-0.58	1	1
DKK2	-0.007	0.12	-10000	0	-0.68	15	15
TLE1	0.003	0.014	-10000	0	-10000	0	0
MACF1	0.014	0.001	-10000	0	-10000	0	0
CTNNB1	0.037	0.11	-10000	0	-0.41	2	2
WIF1	-0.26	0.3	-10000	0	-0.59	233	233
beta catenin/RanBP3	-0.012	0.086	0.37	11	-10000	0	11
KREMEN2	-0.27	0.39	-10000	0	-0.81	180	180
DKK1	-0.29	0.39	-10000	0	-0.79	195	195
beta catenin/beta TrCP1	0.043	0.1	-10000	0	-10000	0	0
FZD1	0.005	0.084	-10000	0	-0.77	6	6
AXIN2	-0.011	0.2	-10000	0	-1.4	11	11
AXIN1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.082	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.006	0.041	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.051	0.076	-10000	0	-10000	0	0
HNF1A	-0.013	0.11	-10000	0	-0.81	10	10
CTBP1	0.003	0.015	-10000	0	-10000	0	0
MYC	0.013	0.045	-10000	0	-0.53	1	1
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.2	0.26	-10000	0	-0.54	187	187
NKD1	-0.017	0.15	-10000	0	-0.77	20	20
TCF4	0.003	0.015	-10000	0	-10000	0	0
TCF3	0.003	0.015	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.012	0.075	-10000	0	-0.48	12	12
Ran/GTP	0.001	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.012	0.089	0.4	21	-10000	0	21
LEF1	-0.004	0.075	-10000	0	-0.75	5	5
DVL1	0.066	0.052	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.091	0.073	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.37	0.35	-10000	0	-0.63	306	306
LRP6	0.013	0.026	-10000	0	-0.58	1	1
CSNK1A1	0.003	0.017	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.004	0.15	-10000	0	-0.85	13	13
WNT1	0	0.094	-10000	0	-0.81	7	7
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
PPP2R5D	0.05	0.067	0.36	20	-10000	0	20
APC	0.028	0.077	-10000	0	-0.45	12	12
WNT1/LRP6/FZD1	0.11	0.12	0.24	230	-10000	0	230
CREBBP	0.003	0.015	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.084	0.14	-10000	0	-0.5	4	4
regulation of S phase of mitotic cell cycle	-0.045	0.12	-10000	0	-10000	0	0
GNAO1	0.008	0.067	-10000	0	-0.75	4	4
HRAS	0.012	0.036	-10000	0	-0.81	1	1
SHBG/T-DHT	-0.001	0.034	-10000	0	-0.55	2	2
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.042	0.14	-10000	0	-0.51	2	2
T-DHT/AR	-0.12	0.19	-10000	0	-0.43	140	140
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	67	67
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.026	-10000	0	-0.58	1	1
mol:GDP	-0.12	0.19	-10000	0	-0.44	140	140
cell proliferation	-0.051	0.18	-10000	0	-0.58	19	19
PIK3CA	0.014	0	-10000	0	-10000	0	0
FOS	-0.086	0.29	-10000	0	-0.82	67	67
mol:Ca2+	-0.014	0.021	-10000	0	-0.088	10	10
MAPK3	-0.045	0.16	-10000	0	-0.49	19	19
MAPK1	-0.019	0.091	-10000	0	-0.27	19	19
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
mol:IP3	0	0.002	-10000	0	-0.004	67	67
cAMP biosynthetic process	0.011	0.039	-10000	0	-0.51	2	2
GNG2	0.014	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	67	67
HRAS/GTP	-0.08	0.13	-10000	0	-0.46	5	5
actin cytoskeleton reorganization	-0.001	0.017	-10000	0	-10000	0	0
SRC	0.013	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	67	67
PI3K	-0.001	0.022	-10000	0	-0.35	2	2
apoptosis	0.043	0.17	0.42	67	-10000	0	67
T-DHT/AR/PELP1	-0.097	0.16	-10000	0	-0.36	140	140
HRAS/GDP	-0.11	0.18	-10000	0	-0.41	141	141
CREB1	-0.048	0.18	-10000	0	-0.45	67	67
RAC1-CDC42/GTP	-0.001	0.017	-10000	0	-10000	0	0
AR	-0.15	0.26	-10000	0	-0.58	140	140
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.05	0.14	-10000	0	-0.45	5	5
RAC1-CDC42/GDP	-0.1	0.17	-10000	0	-0.39	140	140
T-DHT/AR/PELP1/Src	-0.086	0.14	-10000	0	-0.5	4	4
MAP2K2	-0.042	0.14	-10000	0	-0.51	2	2
T-DHT/AR/PELP1/Src/PI3K	-0.045	0.12	-10000	0	-10000	0	0
GNAZ	-0.014	0.14	-10000	0	-0.74	19	19
SHBG	0.01	0.051	-10000	0	-0.81	2	2
Gi family/GNB1/GNG2/GDP	0.012	0.068	-10000	0	-0.45	1	1
mol:T-DHT	0	0.001	-10000	0	-0.003	48	48
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	-0.015	0.13	-10000	0	-0.62	22	22
Gi family/GTP	-0.044	0.079	-10000	0	-0.37	8	8
CDC42	0.014	0	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.014	0.077	-10000	0	-10000	0	0
epithelial cell differentiation	-0.071	0.12	-10000	0	-0.57	4	4
ITCH	0.027	0.019	-10000	0	-10000	0	0
WWP1	-0.009	0.071	-10000	0	-10000	0	0
FYN	0.012	0.036	-10000	0	-0.81	1	1
EGFR	-0.015	0.15	-10000	0	-0.76	19	19
PRL	-0.003	0.079	-10000	0	-0.81	5	5
neuron projection morphogenesis	-0.028	0.16	-10000	0	-10000	0	0
PTPRZ1	-0.011	0.12	-10000	0	-0.58	22	22
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.082	0.16	-10000	0	-0.51	27	27
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.08	0.2	-10000	0	-0.52	78	78
ADAM17	0.025	0.042	-10000	0	-0.57	2	2
ErbB4/ErbB4	-0.023	0.092	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.032	0.087	-10000	0	-0.49	5	5
NCOR1	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.069	0.19	-10000	0	-0.49	78	78
GRIN2B	-0.067	0.18	-10000	0	-0.53	28	28
ErbB4/ErbB2/betacellulin	-0.098	0.16	-10000	0	-0.62	3	3
STAT1	-0.033	0.19	-10000	0	-0.79	30	30
HBEGF	0.014	0	-10000	0	-10000	0	0
PRLR	-0.11	0.24	-10000	0	-0.58	104	104
E4ICDs/ETO2	-0.015	0.078	-10000	0	-10000	0	0
axon guidance	-0.015	0.087	-10000	0	-0.4	2	2
NEDD4	0.027	0.019	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.091	0.18	-10000	0	-0.44	107	107
CBFA2T3	0.012	0.026	-10000	0	-0.58	1	1
ErbB4/ErbB2/HBEGF	0.005	0.071	-10000	0	-0.52	3	3
MAPK3	-0.037	0.17	-10000	0	-0.47	27	27
STAT1 (dimer)	-0.044	0.15	-10000	0	-0.56	29	29
MAPK1	-0.037	0.17	-10000	0	-0.47	27	27
JAK2	0.012	0.026	-10000	0	-0.58	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.071	0.19	-10000	0	-0.49	80	80
NRG1	-0.07	0.24	-10000	0	-0.6	84	84
NRG3	-0.002	0.08	-10000	0	-0.68	7	7
NRG2	-0.32	0.29	-10000	0	-0.58	296	296
NRG4	-0.028	0.15	-10000	0	-0.6	35	35
heart development	-0.015	0.087	-10000	0	-0.4	2	2
neural crest cell migration	-0.07	0.19	-10000	0	-0.48	80	80
ERBB2	0.027	0.057	-10000	0	-0.53	5	5
WWOX/E4ICDs	-0.014	0.077	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.071	0.13	-10000	0	-0.47	35	35
apoptosis	0.066	0.087	0.55	4	-10000	0	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.22	0.19	-10000	0	-0.46	100	100
ErbB4/ErbB2/epiregulin	-0.085	0.17	-10000	0	-0.6	8	8
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.18	-10000	0	-0.46	52	52
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.087	0.13	-10000	0	-0.65	4	4
MDM2	-0.011	0.079	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.089	0.17	-10000	0	-0.49	77	77
STAT5A	-0.006	0.082	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.085	0.2	-10000	0	-0.5	90	90
DLG4	0.012	0.026	-10000	0	-0.58	1	1
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.037	0.054	-10000	0	-10000	0	0
STAT5A (dimer)	-0.075	0.12	-10000	0	-0.62	4	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.081	-10000	0	-10000	0	0
LRIG1	-0.001	0.092	-10000	0	-0.58	13	13
EREG	-0.15	0.27	-10000	0	-0.58	144	144
BTC	-0.17	0.27	-10000	0	-0.58	162	162
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.015	0.088	-10000	0	-0.4	2	2
ERBB4	-0.023	0.093	-10000	0	-10000	0	0
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.019	0.057	-10000	0	-0.39	10	10
GRB2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.019	0.11	-10000	0	-0.5	6	6
glial cell differentiation	0.037	0.053	-10000	0	-10000	0	0
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.14	0.22	-10000	0	-0.66	44	44

×

BCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.029	0.15	-9999	-0.43	30	30
IKBKB	-0.009	0.079	-9999	-0.28	3	3
AKT1	-0.027	0.12	-9999	-0.29	43	43
IKBKG	-0.008	0.082	-9999	-0.29	7	7
CALM1	-0.045	0.12	-9999	-0.4	33	33
PIK3CA	0.014	0	-9999	-10000	0	0
MAP3K1	-0.057	0.21	-9999	-0.63	34	34
MAP3K7	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.056	0.13	-9999	-0.42	35	35
DOK1	0.012	0.036	-9999	-0.81	1	1
AP-1	-0.022	0.097	-9999	-0.27	12	12
LYN	0.012	0.036	-9999	-0.81	1	1
BLNK	-0.043	0.17	-9999	-0.58	50	50
SHC1	0.014	0	-9999	-10000	0	0
BCR complex	-0.14	0.29	-9999	-0.65	111	111
CD22	-0.12	0.27	-9999	-0.82	56	56
CAMK2G	-0.035	0.11	-9999	-0.4	17	17
CSNK2A1	0.014	0	-9999	-10000	0	0
INPP5D	0.011	0.037	-9999	-0.58	2	2
SHC/GRB2/SOS1	-0.11	0.2	-9999	-0.66	33	33
GO:0007205	-0.056	0.13	-9999	-0.43	35	35
SYK	0.01	0.045	-9999	-0.58	3	3
ELK1	-0.047	0.12	-9999	-0.41	34	34
NFATC1	-0.067	0.19	-9999	-0.48	72	72
B-cell antigen/BCR complex	-0.14	0.29	-9999	-0.65	111	111
PAG1/CSK	-0.002	0.038	-9999	-0.62	2	2
NFKBIB	0.008	0.03	-9999	-10000	0	0
HRAS	-0.049	0.14	-9999	-0.44	33	33
NFKBIA	0.008	0.029	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.014	0.025	-9999	-10000	0	0
RasGAP/Csk	-0.11	0.22	-9999	-0.56	84	84
mol:GDP	-0.054	0.12	-9999	-0.41	35	35
PTEN	0.014	0	-9999	-10000	0	0
CD79B	-0.025	0.17	-9999	-0.73	27	27
NF-kappa-B/RelA/I kappa B alpha	0.014	0.024	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.091	0.23	-9999	-0.55	81	81
PIK3R1	0.011	0.037	-9999	-0.58	2	2
mol:IP3	-0.057	0.13	-9999	-0.44	35	35
CSK	0.014	0	-9999	-10000	0	0
FOS	-0.072	0.16	-9999	-0.43	53	53
CHUK	-0.008	0.082	-9999	-0.29	7	7
IBTK	0.014	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.07	0.13	-9999	-0.57	16	16
PTPN6	-0.11	0.25	-9999	-0.76	56	56
RELA	0.014	0	-9999	-10000	0	0
BCL2A1	0.008	0.038	-9999	-0.13	30	30
VAV2	-0.15	0.27	-9999	-0.75	75	75
ubiquitin-dependent protein catabolic process	0.012	0.029	-9999	-10000	0	0
BTK	-0.004	0.031	-9999	-10000	0	0
CD19	-0.15	0.3	-9999	-0.78	83	83
MAP4K1	-0.007	0.13	-9999	-0.76	14	14
CD72	-0.071	0.25	-9999	-0.8	54	54
PAG1	0.01	0.051	-9999	-0.81	2	2
MAPK14	-0.038	0.18	-9999	-0.52	33	33
SH3BP5	0.01	0.045	-9999	-0.58	3	3
PIK3AP1	-0.063	0.16	-9999	-0.48	49	49
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.083	0.2	-9999	-0.58	46	46
RAF1	-0.039	0.13	-9999	-0.41	32	32
RasGAP/p62DOK/SHIP	-0.1	0.22	-9999	-0.79	27	27
CD79A	-0.14	0.31	-9999	-0.74	106	106
re-entry into mitotic cell cycle	-0.022	0.097	-9999	-0.27	12	12
RASA1	0.011	0.037	-9999	-0.58	2	2
MAPK3	-0.018	0.11	-9999	-0.42	3	3
MAPK1	-0.018	0.11	-9999	-0.42	3	3
CD72/SHP1	-0.11	0.3	-9999	-0.83	57	57
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.042	0.18	-9999	-0.51	35	35
actin cytoskeleton organization	-0.09	0.24	-9999	-0.62	74	74
NF-kappa-B/RelA	0.034	0.047	-9999	-10000	0	0
Calcineurin	-0.047	0.089	-9999	-0.44	3	3
PI3K	-0.13	0.22	-9999	-0.62	72	72
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.069	0.13	-9999	-0.47	36	36
SOS1	0.014	0	-9999	-10000	0	0
Bam32/HPK1	-0.062	0.22	-9999	-0.73	40	40
DAPP1	-0.091	0.21	-9999	-0.73	38	38
cytokine secretion	-0.061	0.18	-9999	-0.45	72	72
mol:DAG	-0.057	0.13	-9999	-0.44	35	35
PLCG2	0.012	0.026	-9999	-0.58	1	1
MAP2K1	-0.028	0.12	-9999	-0.43	6	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.26	-9999	-0.66	84	84
mol:PI-3-4-5-P3	-0.088	0.15	-9999	-0.41	70	70
ETS1	-0.027	0.11	-9999	-0.42	6	6
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.23	-9999	-0.56	93	93
B-cell antigen/BCR complex/LYN	-0.093	0.2	-9999	-0.73	31	31
MALT1	0.014	0	-9999	-10000	0	0
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	-0.099	0.26	-9999	-0.67	74	74
B-cell antigen/BCR complex/LYN/SYK	-0.13	0.27	-9999	-0.89	46	46
CARD11	-0.073	0.17	-9999	-0.49	58	58
FCGR2B	0.006	0.068	-9999	-0.58	7	7
PPP3CA	0.014	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
IKK complex	0.007	0.039	-9999	-10000	0	0
PTPRC	-0.003	0.11	-9999	-0.69	12	12
PDPK1	-0.028	0.12	-9999	-0.29	43	43
PPP3CB	0.014	0	-9999	-10000	0	0
PPP3CC	0.014	0	-9999	-10000	0	0
POU2F2	0.008	0.04	-9999	-0.14	31	31

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.062	0.19	0.59	54	-10000	0	54
KIRREL	-0.022	0.14	-10000	0	-0.63	25	25
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.062	0.19	-10000	0	-0.59	54	54
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.057	0.17	-10000	0	-0.56	43	43
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.009	0.12	-10000	0	-0.6	10	10
FYN	-0.036	0.16	-10000	0	-0.51	44	44
mol:Ca2+	-0.056	0.17	-10000	0	-0.56	43	43
mol:DAG	-0.056	0.17	-10000	0	-0.56	43	43
NPHS2	-0.024	0.13	-10000	0	-0.84	13	13
mol:IP3	-0.056	0.17	-10000	0	-0.56	43	43
regulation of endocytosis	-0.049	0.15	-10000	0	-0.5	37	37
Nephrin/NEPH1/podocin/Cholesterol	-0.058	0.17	-10000	0	-0.57	43	43
establishment of cell polarity	-0.062	0.19	-10000	0	-0.59	54	54
Nephrin/NEPH1/podocin/NCK1-2	-0.052	0.16	-10000	0	-0.54	36	36
Nephrin/NEPH1/beta Arrestin2	-0.026	0.16	-10000	0	-0.5	37	37
NPHS1	-0.048	0.2	-10000	0	-0.82	33	33
Nephrin/NEPH1/podocin	-0.051	0.16	-10000	0	-0.52	44	44
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.014	0	-10000	0	-10000	0	0
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.057	0.17	-10000	0	-0.56	43	43
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.057	0.17	-10000	0	-0.56	43	43
GRB2	0.014	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.055	0.2	-10000	0	-0.53	65	65
cytoskeleton organization	-0.013	0.15	-10000	0	-0.77	10	10
Nephrin/NEPH1	-0.047	0.14	-10000	0	-0.44	54	54
Nephrin/NEPH1/ZO-1	-0.051	0.15	-10000	0	-0.55	37	37

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.012	0.069	-10000	0	-0.8	3	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.063	0.19	0.63	29	-10000	0	29
IL27/IL27R/JAK1	-0.11	0.21	-10000	0	-0.83	21	21
TBX21	-0.11	0.26	-10000	0	-0.73	40	40
IL12B	-0.059	0.23	-10000	0	-0.81	44	44
IL12A	-0.009	0.095	-10000	0	-0.48	20	20
IL6ST	-0.064	0.2	-10000	0	-0.59	65	65
IL27RA/JAK1	-0.014	0.12	-10000	0	-0.59	16	16
IL27	-0.029	0.17	-10000	0	-0.82	23	23
TYK2	0.011	0.037	-10000	0	-0.82	1	1
T-helper cell lineage commitment	-0.017	0.12	-10000	0	-0.68	7	7
T-helper 2 cell differentiation	0.063	0.19	0.63	29	-10000	0	29
T cell proliferation during immune response	0.063	0.19	0.63	29	-10000	0	29
MAPKKK cascade	-0.063	0.19	-10000	0	-0.63	29	29
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.014	0	-10000	0	-10000	0	0
STAT1	-0.034	0.19	-10000	0	-0.8	30	30
IL12RB1	-0.049	0.21	-10000	0	-0.8	39	39
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.17	0.32	-10000	0	-0.67	128	128
IL27/IL27R/JAK2/TYK2	-0.064	0.19	-10000	0	-0.64	29	29
positive regulation of T cell mediated cytotoxicity	-0.063	0.19	-10000	0	-0.63	29	29
STAT1 (dimer)	-0.19	0.3	0.52	1	-0.92	44	45
JAK2	0.011	0.027	-10000	0	-0.58	1	1
JAK1	0.013	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.053	0.18	-10000	0	-0.61	28	28
T cell proliferation	-0.084	0.21	-10000	0	-0.6	44	44
IL12/IL12R/TYK2/JAK2	-0.058	0.18	-10000	0	-0.64	19	19
IL17A	-0.018	0.12	-10000	0	-0.68	7	7
mast cell activation	0.063	0.19	0.63	29	-10000	0	29
IFNG	-0.018	0.049	-10000	0	-0.11	107	107
T cell differentiation	-0.007	0.009	-10000	0	-0.024	72	72
STAT3 (dimer)	-0.053	0.18	-10000	0	-0.62	27	27
STAT5A (dimer)	-0.053	0.18	-10000	0	-0.62	27	27
STAT4 (dimer)	-0.065	0.2	-10000	0	-0.63	36	36
STAT4	-0.008	0.13	-10000	0	-0.79	14	14
T cell activation	-0.006	0.02	0.092	20	-10000	0	20
IL27R/JAK2/TYK2	-0.056	0.17	-10000	0	-0.75	9	9
GATA3	0.002	0.15	-10000	0	-0.68	20	20
IL18	-0.004	0.082	-10000	0	-0.42	19	19
positive regulation of mast cell cytokine production	-0.052	0.18	-10000	0	-0.6	27	27
IL27/EBI3	-0.029	0.16	-10000	0	-0.63	32	32
IL27RA	-0.023	0.13	-10000	0	-0.63	20	20
IL6	-0.046	0.19	-10000	0	-0.62	51	51
STAT5A	0.014	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.018	0.07	-10000	0	-10000	0	0
IL1B	-0.051	0.19	-10000	0	-0.61	52	52
EBI3	-0.004	0.1	-10000	0	-0.72	10	10
TNF	-0.017	0.13	-10000	0	-0.6	25	25

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.009	0.061	-10000	0	-0.59	4	4
HDAC1	0.01	0.005	-10000	0	-10000	0	0
AES	0.012	0.001	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	0.01	0.051	-10000	0	-0.65	3	3
LRP6/FZD1	-0.008	0.065	-10000	0	-0.56	7	7
TLE1	0.013	0.001	-10000	0	-10000	0	0
AP1	-0.024	0.12	-10000	0	-0.29	82	82
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.011	0.037	-10000	0	-0.58	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.039	0.046	-10000	0	-10000	0	0
NICD/RBPSUH	-0.005	0.053	-10000	0	-0.58	4	4
WIF1	-0.26	0.3	-10000	0	-0.59	233	233
NOTCH1	-0.006	0.056	-10000	0	-0.62	4	4
PSENEN	0.01	0.051	-10000	0	-0.81	2	2
KREMEN2	-0.27	0.39	-10000	0	-0.81	180	180
DKK1	-0.29	0.39	-10000	0	-0.79	195	195
beta catenin/beta TrCP1	0.02	0.045	-10000	0	-0.35	1	1
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	0.001	0.025	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.019	0.044	-10000	0	-10000	0	0
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.063	0.2	-10000	0	-0.58	67	67
JUN	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.012	0.002	-10000	0	-10000	0	0
CTNNB1	0.013	0.048	-10000	0	-0.37	1	1
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.2	0.26	-10000	0	-0.54	187	187
HNF1A	-0.003	0.11	-10000	0	-0.81	10	10
CTBP1	0.012	0.001	-10000	0	-10000	0	0
MYC	0.025	0.013	-10000	0	-10000	0	0
NKD1	-0.017	0.15	-10000	0	-0.77	20	20
FZD1	0.005	0.084	-10000	0	-0.77	6	6
NOTCH1 precursor/Deltex homolog 1	-0.007	0.064	-10000	0	-0.61	5	5
apoptosis	-0.023	0.12	-10000	0	-0.29	82	82
Delta 1/NOTCHprecursor	-0.009	0.06	-10000	0	-0.58	4	4
DLL1	0.007	0.063	-10000	0	-0.58	6	6
PPARD	0.025	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.002	0.028	-10000	0	-0.45	2	2
APC	0.001	0.031	-10000	0	-0.35	2	2
DVL1	-0.019	0.028	-10000	0	-10000	0	0
CSNK2A1	0.014	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.37	0.35	-10000	0	-0.63	306	306
LRP6	0.012	0.026	-10000	0	-0.58	1	1
CSNK1A1	0.014	0.001	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.006	0.14	-10000	0	-0.82	13	13
WNT1	-0.001	0.094	-10000	0	-0.81	7	7
Axin1/APC/beta catenin	0.025	0.042	-10000	0	-0.4	1	1
DKK2	-0.007	0.12	-10000	0	-0.68	15	15
NOTCH1 precursor/DVL1	-0.01	0.052	-10000	0	-0.58	4	4
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.007	0.064	-10000	0	-0.62	5	5
PPP2R5D	0.002	0.066	0.32	20	-10000	0	20
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.16	0.17	-10000	0	-0.52	29	29
RBPJ	0.014	0	-10000	0	-10000	0	0
CREBBP	0.017	0.003	-10000	0	-10000	0	0

×

Ephrin B reverse 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
EFNB2	0.012	0.026	-10000	0	-0.58	1	1
EPHB2	-0.2	0.36	-10000	0	-0.8	138	138
EFNB1	-0.023	0.16	-10000	0	-0.62	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.16	0.23	-10000	0	-0.82	21	21
Ephrin B2/EPHB1-2	-0.15	0.23	-10000	0	-0.5	155	155
neuron projection morphogenesis	-0.16	0.22	-10000	0	-0.78	21	21
Ephrin B1/EPHB1-2/Tiam1	-0.17	0.26	-10000	0	-0.89	21	21
DNM1	-0.045	0.21	-10000	0	-0.81	37	37
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.007	0.09	-10000	0	-0.6	11	11
YES1	-0.016	0.12	-10000	0	-0.84	11	11
Ephrin B1/EPHB1-2/NCK2	-0.17	0.25	-10000	0	-0.9	19	19
PI3K	0.006	0.096	-10000	0	-0.63	11	11
mol:GDP	-0.17	0.25	-10000	0	-0.87	21	21
ITGA2B	-0.069	0.25	-10000	0	-0.81	52	52
endothelial cell proliferation	-0.001	0.016	-10000	0	-0.35	1	1
FYN	-0.016	0.12	-10000	0	-0.84	11	11
MAP3K7	-0.013	0.093	-10000	0	-0.64	11	11
FGR	-0.016	0.12	-10000	0	-0.83	11	11
TIAM1	0.007	0.063	-10000	0	-0.58	6	6
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
RGS3	0.014	0	-10000	0	-10000	0	0
cell adhesion	-0.04	0.19	-10000	0	-0.52	54	54
LYN	-0.016	0.12	-10000	0	-0.84	11	11
Ephrin B1/EPHB1-2/Src Family Kinases	-0.018	0.11	-10000	0	-0.78	11	11
Ephrin B1/EPHB1-2	-0.02	0.1	-10000	0	-0.7	11	11
SRC	-0.016	0.12	-10000	0	-0.83	11	11
ITGB3	-0.017	0.15	-10000	0	-0.73	21	21
EPHB1	-0.03	0.18	-10000	0	-0.73	30	30
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.016	-10000	0	-0.36	1	1
alphaIIb/beta3 Integrin	-0.083	0.22	-10000	0	-0.62	70	70
BLK	-0.032	0.12	-10000	0	-0.83	11	11
HCK	-0.016	0.12	-10000	0	-0.83	11	11
regulation of stress fiber formation	0.17	0.25	0.88	19	-10000	0	19
MAPK8	0.011	0.1	-10000	0	-0.64	11	11
Ephrin B1/EPHB1-2/RGS3	-0.17	0.25	-10000	0	-0.57	71	71
endothelial cell migration	-0.007	0.079	-10000	0	-0.54	11	11
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	-0.004	0.1	-10000	0	-0.69	11	11
regulation of focal adhesion formation	0.17	0.25	0.88	19	-10000	0	19
chemotaxis	0.17	0.25	0.49	172	-10000	0	172
PIK3CA	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.16	0.23	-10000	0	-0.81	21	21
angiogenesis	-0.019	0.1	-10000	0	-0.69	11	11
LCK	-0.019	0.12	-10000	0	-0.83	11	11

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.029	0.033	-9999	-10000	0	0
SNTA1	0.012	0.036	-9999	-0.81	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.024	0.059	-9999	-0.53	4	4
MAPK12	-0.007	0.14	-9999	-0.55	21	21
CCND1	0	0.086	-9999	-0.37	15	15
p38 gamma/SNTA1	0	0.13	-9999	-0.51	22	22
MAP2K3	0.012	0.026	-9999	-0.58	1	1
PKN1	0.01	0.051	-9999	-0.81	2	2
G2/M transition checkpoint	-0.006	0.13	-9999	-0.55	21	21
MAP2K6	0.006	0.086	-9999	-0.35	26	26
MAPT	-0.14	0.18	-9999	-0.32	241	241
MAPK13	0.021	0.038	-9999	-0.42	4	4
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.016	0.029	-9999	-0.36	3	3

×

Regulation of nuclear SMAD2/3 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
EP300	0.007	0.028	-10000	0	-0.58	1	1
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.035	0.15	-10000	0	-0.52	16	16
AKT1	0	0.033	-10000	0	-10000	0	0
GSC	-0.016	0.19	-10000	0	-0.7	32	32
NKX2-5	-0.16	0.31	-10000	0	-0.71	123	123
muscle cell differentiation	0.13	0.21	0.64	52	-10000	0	52
SMAD2-3/SMAD4/SP1	-0.04	0.1	-10000	0	-10000	0	0
SMAD4	0.002	0.043	-10000	0	-0.55	1	1
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.015	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	0	0.063	-10000	0	-0.53	6	6
SMAD3/SMAD4/VDR	0.005	0.039	-10000	0	-10000	0	0
MYC	0.028	0.034	-10000	0	-10000	0	0
CDKN2B	-0.25	0.58	-10000	0	-1.4	111	111
AP1	-0.004	0.1	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.056	0.041	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.063	0.16	-10000	0	-0.56	14	14
SP3	0.016	0	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.1	0.29	-10000	0	-0.8	74	74
SMAD3/SMAD4/GR	0.028	0.063	-10000	0	-10000	0	0
GATA3	-0.015	0.15	-10000	0	-0.76	20	20
SKI/SIN3/HDAC complex/NCoR1	0.055	0.023	-10000	0	-10000	0	0
MEF2C/TIF2	-0.16	0.28	-10000	0	-0.76	54	54
endothelial cell migration	0.36	0.33	0.64	297	-10000	0	297
MAX	0.035	0.02	-10000	0	-10000	0	0
RBBP7	0.015	0.002	-10000	0	-10000	0	0
RBBP4	0.013	0.026	-10000	0	-0.58	1	1
RUNX2	0.01	0.051	-10000	0	-0.65	3	3
RUNX3	0.002	0.095	-10000	0	-0.81	7	7
RUNX1	0.014	0	-10000	0	-10000	0	0
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.035	0.02	-10000	0	-10000	0	0
VDR	0.011	0.037	-10000	0	-0.58	2	2
CDKN1A	0.021	0.093	-10000	0	-10000	0	0
KAT2B	-0.019	0.13	-10000	0	-0.58	26	26
SMAD2/SMAD2/SMAD4/FOXH1	-0.073	0.2	-10000	0	-0.55	74	74
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.015	0.002	-10000	0	-10000	0	0
SERPINE1	-0.36	0.33	-10000	0	-0.64	297	297
SMAD3/SMAD4/ATF2	0.007	0.046	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.001	0.073	-10000	0	-0.52	5	5
SAP30	0.013	0.036	-10000	0	-0.8	1	1
Cbp/p300/PIAS3	0.004	0.034	-10000	0	-10000	0	0
JUN	0.017	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.013	0.12	-10000	0	-0.58	16	16
TFE3	0	0.019	-10000	0	-10000	0	0
COL1A2	-0.24	0.34	-10000	0	-0.68	192	192
mesenchymal cell differentiation	-0.005	0.056	0.5	2	-10000	0	2
DLX1	-0.31	0.4	-10000	0	-0.8	203	203
TCF3	0.014	0	-10000	0	-10000	0	0
FOS	-0.056	0.2	-10000	0	-0.57	67	67
SMAD3/SMAD4/Max	0.028	0.063	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.004	0.021	-10000	0	-10000	0	0
ZBTB17	0.024	0.026	-10000	0	-10000	0	0
LAMC1	0.011	0.043	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.006	0.057	-10000	0	-0.59	2	2
IRF7	-0.015	0.15	-10000	0	-0.8	18	18
ESR1	-0.01	0.16	-10000	0	-0.68	28	28
HNF4A	-0.07	0.24	-10000	0	-0.81	51	51
MEF2C	-0.13	0.27	-10000	0	-0.62	69	69
SMAD2-3/SMAD4	-0.004	0.058	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.006	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	-0.002	0.012	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0.051	-10000	0	-0.81	2	2
CREBBP	0.008	0.01	-10000	0	-10000	0	0
SKIL	0.012	0.036	-10000	0	-0.81	1	1
HDAC1	0.015	0.002	-10000	0	-10000	0	0
HDAC2	0.015	0.002	-10000	0	-10000	0	0
SNIP1	0.016	0.004	-10000	0	-10000	0	0
GCN5L2	-0.009	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.002	0.045	-10000	0	-10000	0	0
MSG1/HSC70	0.01	0.07	-10000	0	-0.62	6	6
SMAD2	0	0.038	-10000	0	-10000	0	0
SMAD3	0.007	0.04	-10000	0	-0.53	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.02	0.046	-10000	0	-0.45	1	1
SMAD2/SMAD2/SMAD4	-0.023	0.081	-10000	0	-0.35	27	27
NCOR1	0.015	0.002	-10000	0	-10000	0	0
NCOA2	-0.034	0.16	-10000	0	-0.58	42	42
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.073	0.16	-10000	0	-0.42	89	89
SMAD2-3/SMAD4/SP1/MIZ-1	-0.031	0.095	-10000	0	-10000	0	0
IFNB1	0.006	0.15	-10000	0	-0.68	16	16
SMAD3/SMAD4/MEF2C	-0.13	0.26	-10000	0	-0.69	44	44
CITED1	0.004	0.088	-10000	0	-0.81	6	6
SMAD2-3/SMAD4/ARC105	0.003	0.061	-10000	0	-0.49	2	2
RBL1	0.012	0.026	-10000	0	-0.58	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.067	0.22	-10000	0	-0.49	107	107
RUNX1-3/PEBPB2	-0.007	0.061	-10000	0	-0.53	7	7
SMAD7	-0.022	0.11	-10000	0	-10000	0	0
MYC/MIZ-1	0.034	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.12	0.16	0.36	4	-0.41	2	6
IL10	0.013	0.15	-10000	0	-0.6	22	22
PIASy/HDAC complex	0.023	0.013	-10000	0	-10000	0	0
PIAS3	0.008	0.008	-10000	0	-10000	0	0
CDK2	0.007	0.01	-10000	0	-10000	0	0
IL5	0.011	0.13	-10000	0	-0.57	14	14
CDK4	0.008	0.011	-10000	0	-10000	0	0
PIAS4	0.023	0.013	-10000	0	-10000	0	0
ATF3	0.003	0.084	-10000	0	-0.66	8	8
SMAD3/SMAD4/SP1	-0.047	0.091	-10000	0	-10000	0	0
FOXG1	-0.11	0.27	-10000	0	-0.73	83	83
FOXO3	0.007	0.044	-10000	0	-10000	0	0
FOXO1	0.007	0.044	-10000	0	-10000	0	0
FOXO4	0.005	0.051	-10000	0	-0.41	2	2
heart looping	-0.13	0.26	-10000	0	-0.62	69	69
CEBPB	0.007	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.21	0.28	-10000	0	-0.56	201	201
MYOD1	-0.095	0.22	-10000	0	-0.59	89	89
SMAD3/SMAD4/HNF4	-0.049	0.17	-10000	0	-0.56	51	51
SMAD3/SMAD4/GATA3	-0.014	0.12	-10000	0	-0.56	17	17
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.036	-10000	0	-0.81	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.008	0.067	-10000	0	-0.47	4	4
SMAD3/SMAD4/SP1-3	-0.025	0.082	-10000	0	-10000	0	0
MED15	0.01	0.051	-10000	0	-0.81	2	2
SP1	-0.034	0.073	-10000	0	-10000	0	0
SIN3B	0.015	0.002	-10000	0	-10000	0	0
SIN3A	0.015	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.16	0.27	-10000	0	-0.55	136	136
ITGB5	0.009	0.09	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.089	0.17	-10000	0	-0.44	31	31
AR	-0.15	0.26	-10000	0	-0.58	140	140
negative regulation of cell growth	0.023	0.054	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.059	0.15	-10000	0	-0.42	37	37
E2F5	0.01	0.045	-10000	0	-0.58	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.062	0.17	-10000	0	-0.49	42	42
SMAD2-3/SMAD4/FOXO1-3a-4	-0.035	0.15	-10000	0	-10000	0	0
TFDP1	0.012	0.036	-10000	0	-0.81	1	1
SMAD3/SMAD4/AP1	0	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.005	0.056	-10000	0	-0.5	2	2
TGIF2	0.01	0.051	-10000	0	-0.81	2	2
TGIF1	0.012	0.036	-10000	0	-0.81	1	1
ATF2	0.012	0.026	-10000	0	-0.58	1	1

×

IL1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.012	0.026	-9999	-0.58	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.023	0.071	-9999	-0.52	2	2
IRAK/TOLLIP	0.033	0.004	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
IKBKG	0.014	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.24	0.29	-9999	-0.56	222	222
IL1A	-0.2	0.36	-9999	-0.8	134	134
IL1B	-0.039	0.19	-9999	-0.6	53	53
IRAK/TRAF6/p62/Atypical PKCs	0	0.011	-9999	-10000	0	0
IL1R2	-0.11	0.24	-9999	-0.59	103	103
IL1R1	0.012	0.026	-9999	-0.58	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.023	0.073	-9999	-0.73	1	1
TOLLIP	0.014	0	-9999	-10000	0	0
TICAM2	0.013	0.001	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.071	0.005	-9999	-10000	0	0
JUN	0.033	0.071	-9999	-0.48	2	2
MAP3K7	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.045	0.13	-9999	-0.84	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.12	0.21	-9999	-0.49	129	129
PIK3R1	0.011	0.037	-9999	-0.58	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.12	0.2	-9999	-0.73	2	2
IL1 beta fragment/IL1R1/IL1RAP	-0.05	0.15	-9999	-0.49	50	50
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.026	0.075	-9999	-0.53	2	2
IRAK1	0.027	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.11	0.18	-9999	-0.42	132	132
IRAK4	0.012	0.026	-9999	-0.58	1	1
PRKCI	0.014	0	-9999	-10000	0	0
TRAF6	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.026	-9999	-0.42	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.014	0.089	-9999	-0.83	1	1
CHUK	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.05	0.15	-9999	-0.49	50	50
IL1 beta/IL1R2	-0.12	0.2	-9999	-0.56	59	59
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.041	0.12	-9999	-0.75	1	1
IRAK3	0.003	0.088	-9999	-0.74	7	7
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.045	0.13	-9999	-0.84	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.039	0.14	-9999	-0.71	2	2
IL1 alpha/IL1R1/IL1RAP	-0.14	0.23	-9999	-0.54	129	129
RELA	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.014	0	-9999	-10000	0	0
MYD88	0.014	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.04	0.003	-9999	-10000	0	0
IL1RAP	0.01	0.051	-9999	-0.65	3	3
UBE2N	0.014	0	-9999	-10000	0	0
IRAK/TRAF6	-0.036	0.11	-9999	-0.68	1	1
CASP1	0.012	0.026	-9999	-0.58	1	1
IL1RN/IL1R2	-0.18	0.26	-9999	-0.5	190	190
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.047	0.14	-9999	-0.46	50	50
TMEM189-UBE2V1	0.01	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.012	0.11	-9999	-0.68	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
IL1RN	-0.14	0.26	-9999	-0.58	132	132
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.022	0.066	-9999	-10000	0	0

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.002	0.11	-9999	-0.81	10	10
Syndecan-3/Src/Cortactin	-0.11	0.14	-9999	-0.56	11	11
Syndecan-3/Neurocan	-0.025	0.1	-9999	-0.44	29	29
POMC	-0.083	0.26	-9999	-0.77	64	64
EGFR	-0.015	0.15	-9999	-0.76	19	19
Syndecan-3/EGFR	-0.017	0.082	-9999	-0.44	17	17
AGRP	0.005	0.006	-9999	-10000	0	0
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.01	0.051	-9999	-0.81	2	2
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.033	0.18	-9999	-0.81	27	27
long-term memory	-0.01	0.064	-9999	-0.42	11	11
Syndecan-3/IL8	-0.094	0.18	-9999	-0.46	105	105
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	-0.012	0.085	-9999	-0.62	10	10
FYN	0.012	0.036	-9999	-0.81	1	1
limb bud formation	-0.002	0.023	-9999	-0.37	2	2
MC4R	0.005	0.036	-9999	-0.81	1	1
SRC	0.014	0	-9999	-10000	0	0
PTN	-0.21	0.29	-9999	-0.58	198	198
FGFR/FGF/Syndecan-3	-0.002	0.023	-9999	-0.37	2	2
neuron projection morphogenesis	-0.12	0.16	-9999	-0.63	14	14
Syndecan-3/AgRP	-0.002	0.022	-9999	-0.35	2	2
Syndecan-3/AgRP/MC4R	-0.002	0.028	-9999	-0.43	1	1
Fyn/Cortactin	-0.013	0.089	-9999	-0.62	11	11
SDC3	-0.002	0.024	-9999	-0.37	2	2
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.092	0.18	-9999	-0.45	105	105
IL8	-0.15	0.33	-9999	-0.8	107	107
Syndecan-3/Fyn/Cortactin	-0.011	0.065	-9999	-0.43	11	11
Syndecan-3/CASK	-0.002	0.022	-9999	-0.35	2	2
alpha-MSH/MC4R	-0.073	0.2	-9999	-0.59	64	64
Gamma Secretase	-0.002	0.028	-9999	-0.45	2	2

×

Integrins in angiogenesis

Figure S47. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S47. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.075	-9999	-0.57	9	9
alphaV beta3 Integrin	-0.036	0.13	-9999	-0.55	25	25
PTK2	-0.006	0.15	-9999	-0.58	10	10
IGF1R	0.012	0.036	-9999	-0.81	1	1
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.037	0.1	-9999	-0.4	33	33
VEGFA	0.002	0.095	-9999	-0.81	7	7
ILK	-0.037	0.1	-9999	-0.4	33	33
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	0	0.11	-9999	-0.49	4	4
PTK2B	0.012	0.12	-9999	-0.46	27	27
alphaV/beta3 Integrin/JAM-A	-0.06	0.16	-9999	-0.49	55	55
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.027	0.12	-9999	-0.54	22	22
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.055	0.12	-9999	-0.51	6	6
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.015	0.084	-9999	-0.42	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.024	0.11	-9999	-0.54	19	19
PI4KA	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.25	0.25	-9999	-0.75	50	50
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.31	0.28	-9999	-0.55	291	291
RPS6KB1	-0.21	0.26	-9999	-0.69	50	50
TLN1	0.01	0.051	-9999	-0.81	2	2
MAPK3	-0.11	0.15	-9999	-0.59	29	29
GPR124	0.009	0.062	-9999	-0.81	3	3
MAPK1	-0.11	0.15	-9999	-0.58	31	31
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
alphaV/beta3 Integrin/Tumstatin	-0.081	0.2	-9999	-0.58	59	59
cell adhesion	-0.023	0.096	-9999	-0.46	19	19
ANGPTL3	0.001	0.062	-9999	-0.81	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.065	-9999	-0.49	9	9
IGF-1R heterotetramer	0.012	0.036	-9999	-0.81	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.011	0.037	-9999	-0.58	2	2
ITGB3	-0.017	0.15	-9999	-0.73	21	21
IGF1	-0.086	0.22	-9999	-0.59	86	86
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.027	0.12	-9999	-0.56	21	21
apoptosis	0.006	0.076	-9999	-0.76	5	5
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.024	0.11	-9999	-0.54	19	19
VCL	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.088	0.2	-9999	-0.58	60	60
CSF1	0.007	0.063	-9999	-0.58	6	6
PIK3C2A	-0.037	0.1	-9999	-0.4	33	33
PI4 Kinase/Pyk2	-0.055	0.14	-9999	-0.74	6	6
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.029	0.11	-9999	-0.49	27	27
FAK1/Vinculin	0.005	0.12	-9999	-0.48	6	6
alphaV beta3/Integrin/ppsTEM5	-0.027	0.12	-9999	-0.56	21	21
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.039	0.2	-9999	-0.81	33	33
BCAR1	0.014	0	-9999	-10000	0	0
FGF2	-0.008	0.12	-9999	-0.63	17	17
F11R	0.007	0.09	-9999	-0.46	18	18
alphaV/beta3 Integrin/Lactadherin	-0.024	0.11	-9999	-0.54	19	19
alphaV/beta3 Integrin/TGFBR2	-0.025	0.11	-9999	-0.54	19	19
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.008	0.055	-9999	-0.48	4	4
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.024	0.1	-9999	-0.5	21	21
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.35	0.41	-9999	-0.81	228	228
alphaV/beta3 Integrin/Pyk2	0.011	0.12	-9999	-0.46	27	27
SDC1	0.014	0	-9999	-10000	0	0
VAV3	0.012	0.1	-9999	-0.5	7	7
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.58	3	3
FAK1/Paxillin	0.005	0.12	-9999	-0.46	7	7
cell migration	0.015	0.12	-9999	-0.43	5	5
ITGAV	0.006	0.076	-9999	-0.76	5	5
PI3K	-0.054	0.14	-9999	-0.71	7	7
SPP1	-0.44	0.41	-9999	-0.81	285	285
KDR	0.011	0.037	-9999	-0.58	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.006	0.076	-9999	-0.76	5	5
COL4A3	-0.079	0.25	-9999	-0.73	64	64
angiogenesis	-0.076	0.17	-9999	-0.66	19	19
Rac1/GTP	-0.024	0.082	-9999	-0.53	3	3
EDIL3	-0.09	0.26	-9999	-0.71	75	75
cell proliferation	-0.025	0.11	-9999	-0.54	19	19

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.15	0.27	-9999	-0.6	136	136
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.051	-9999	-0.81	2	2
TCEB1	0.012	0.036	-9999	-0.81	1	1
HIF1A/p53	0.024	0.041	-9999	-10000	0	0
HIF1A	0.019	0.034	-9999	-10000	0	0
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.039	-9999	-0.45	4	4
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.34	0.39	-9999	-0.76	238	238
ARNT/IPAS	-0.11	0.19	-9999	-0.43	136	136
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.032	-9999	-10000	0	0
CUL2	0.012	0.036	-9999	-0.81	1	1
OS9	0.014	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.003	0.04	-9999	-0.53	3	3
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.026	0.032	-9999	-10000	0	0
PHD1-3/OS9	-0.029	0.11	-9999	-0.48	28	28
HIF1A/RACK1/Elongin B/Elongin C	-0.007	0.041	-9999	-0.55	2	2
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.026	0.032	-9999	-10000	0	0
EGLN3	-0.036	0.19	-9999	-0.77	33	33
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	0.009	0.052	-9999	-0.58	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.037	0.026	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.17	0.22	-9999	-0.43	195	195

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.039	0.16	-9999	-0.73	11	11
FZD6	0.009	0.057	-9999	-0.73	3	3
WNT6	-0.052	0.22	-9999	-0.76	44	44
WNT4	-0.008	0.12	-9999	-0.63	17	17
FZD3	0.006	0.068	-9999	-0.58	7	7
WNT5A	0.005	0.072	-9999	-0.61	7	7
WNT11	-0.075	0.24	-9999	-0.74	61	61

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.038	0.095	-9999	-0.81	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.02	0.054	-9999	-10000	0	0
AP1	-0.07	0.13	-9999	-0.57	11	11
mol:PIP3	-0.046	0.11	-9999	-0.56	6	6
AKT1	0.03	0.083	-9999	-0.52	1	1
PTK2B	0.002	0.073	-9999	-0.3	5	5
RHOA	0.012	0.055	-9999	-0.32	1	1
PIK3CB	0.013	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.073	-9999	-0.46	3	3
MAGI3	0.012	0.026	-9999	-0.58	1	1
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.016	0.11	-9999	-0.61	4	4
HRAS/GDP	-0.001	0.027	-9999	-0.63	1	1
positive regulation of microtubule depolymerization	-0.12	0.16	-9999	-0.42	28	28
NF kappa B1 p50/RelA	-0.031	0.086	-9999	-0.54	4	4
endothelial cell migration	-0.077	0.26	-9999	-0.75	66	66
ADCY4	-0.002	0.12	-9999	-0.44	15	15
ADCY5	-0.048	0.14	-9999	-0.53	17	17
ADCY6	-0.006	0.12	-9999	-0.47	16	16
ADCY7	-0.002	0.12	-9999	-0.44	15	15
ADCY1	-0.009	0.12	-9999	-0.43	16	16
ADCY2	-0.068	0.14	-9999	-0.48	22	22
ADCY3	-0.002	0.12	-9999	-0.44	15	15
ADCY8	-0.009	0.12	-9999	-0.42	19	19
ADCY9	-0.003	0.12	-9999	-0.44	15	15
GSK3B	0.01	0.07	-9999	-10000	0	0
arachidonic acid secretion	0.005	0.11	-9999	-0.42	15	15
GNG2	0.013	0	-9999	-10000	0	0
TRIP6	0.019	0.021	-9999	-10000	0	0
GNAO1	-0.022	0.13	-9999	-0.42	16	16
HRAS	0.012	0.036	-9999	-0.81	1	1
NFKBIA	0.017	0.085	-9999	-0.43	3	3
GAB1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.008	0.1	-9999	-0.89	7	7
JUN	0.013	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.013	0.046	-9999	-0.58	2	2
TIAM1	-0.011	0.12	-9999	-1.1	7	7
PIK3R1	0.011	0.036	-9999	-0.58	2	2
mol:IP3	0.012	0.074	-9999	-0.47	3	3
PLCB3	0.016	0.047	-9999	-0.53	2	2
FOS	-0.063	0.2	-9999	-0.58	67	67
positive regulation of mitosis	0.005	0.11	-9999	-0.42	15	15
LPA/LPA1-2-3	-0.046	0.11	-9999	-0.65	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0	-9999	-10000	0	0
stress fiber formation	0.007	0.086	-9999	-0.39	4	4
GNAZ	-0.036	0.15	-9999	-0.54	21	21
EGFR/PI3K-beta/Gab1	-0.048	0.11	-9999	-0.59	6	6
positive regulation of dendritic cell cytokine production	-0.045	0.11	-9999	-0.64	4	4
LPA/LPA2/MAGI-3	-0.012	0.032	-9999	-0.35	1	1
ARHGEF1	-0.002	0.11	-9999	-0.56	5	5
GNAI2	-0.018	0.12	-9999	-0.38	12	12
GNAI3	-0.018	0.12	-9999	-0.38	12	12
GNAI1	-0.019	0.12	-9999	-0.38	13	13
LPA/LPA3	-0.026	0.076	-9999	-0.43	13	13
LPA/LPA2	-0.015	0.04	-9999	-10000	0	0
LPA/LPA1	-0.053	0.13	-9999	-0.36	77	77
HB-EGF/EGFR	-0.39	0.26	-9999	-0.55	379	379
HBEGF	-0.44	0.29	-9999	-0.62	374	374
mol:DAG	0.012	0.074	-9999	-0.47	3	3
cAMP biosynthetic process	-0.015	0.12	-9999	-0.46	15	15
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
LYN	0.017	0.085	-9999	-0.49	1	1
GNAQ	0.006	0.059	-9999	-0.32	4	4
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.001	0.092	-9999	-0.58	13	13
LPAR1	-0.02	0.11	-9999	-0.6	12	12
IL8	-0.22	0.18	-9999	-0.49	92	92
PTK2	-0.007	0.11	-9999	-0.61	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.016	0.11	-9999	-0.62	4	4
EGFR	-0.015	0.15	-9999	-0.76	19	19
PLCG1	-0.005	0.077	-9999	-0.32	13	13
PLD2	-0.007	0.11	-9999	-0.61	4	4
G12/G13	-0.042	0.1	-9999	-0.6	5	5
PI3K-beta	-0.028	0.07	-9999	-0.55	2	2
cell migration	-0.01	0.046	-9999	-0.28	1	1
SLC9A3R2	0.01	0.051	-9999	-0.81	2	2
PXN	0.007	0.087	-9999	-0.4	4	4
HRAS/GTP	0.005	0.11	-9999	-0.44	13	13
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.58	0.37	-9999	-0.81	374	374
PRKCE	0.012	0.026	-9999	-0.58	1	1
PRKCD	0.019	0.071	-9999	-0.48	2	2
Gi(beta/gamma)	0.002	0.11	-9999	-0.53	5	5
mol:LPA	-0.021	0.069	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.025	0.084	-9999	-0.52	4	4
MAPKKK cascade	0.005	0.11	-9999	-0.42	15	15
contractile ring contraction involved in cytokinesis	0.012	0.055	-9999	-0.32	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.04	0.12	-9999	-0.3	88	88
GNA15	0.005	0.067	-9999	-0.33	14	14
GNA12	0.007	0.072	-9999	-0.81	4	4
GNA13	0.013	0	-9999	-10000	0	0
MAPT	-0.12	0.16	-9999	-0.43	28	28
GNA11	0.004	0.066	-9999	-0.3	17	17
Rac1/GTP	-0.009	0.11	-9999	-0.95	7	7
MMP2	-0.077	0.26	-9999	-0.76	66	66

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.056	0.23	-10000	0	-0.89	21	21
NCK1/PAK1/Dok-R	-0.027	0.089	-10000	0	-0.41	21	21
NCK1/Dok-R	-0.05	0.22	-10000	0	-1.1	21	21
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.006	0.04	0.24	12	-10000	0	12
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.084	0.26	-10000	0	-0.83	53	53
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.044	0.2	-10000	0	-1	21	21
FN1	-0.35	0.41	-10000	0	-0.81	228	228
PLD2	0.034	0.25	-10000	0	-1.1	21	21
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.045	0.18	-10000	0	-0.61	48	48
ELK1	0.047	0.22	-10000	0	-1	21	21
GRB7	0.004	0.084	-10000	0	-0.71	7	7
PAK1	0.012	0.036	-10000	0	-0.81	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.33	0.35	-10000	0	-0.85	133	133
CDKN1A	0.063	0.19	-10000	0	-0.65	11	11
ITGA5	-0.24	0.38	-10000	0	-0.81	164	164
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.051	0.22	-10000	0	-1.1	21	21
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	0.062	0.18	-10000	0	-0.65	21	21
PLG	0.022	0.25	-10000	0	-1.1	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.035	0.2	-10000	0	-0.85	21	21
GRB2	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.012	0.037	-10000	0	-0.58	2	2
ANGPT2	0.019	0.19	-10000	0	-0.6	26	26
BMX	-0.005	0.28	-10000	0	-1.2	21	21
ANGPT1	0.018	0.23	-10000	0	-1.2	14	14
tube development	0.055	0.2	-10000	0	-0.73	13	13
ANGPT4	0.008	0.007	-10000	0	-10000	0	0
response to hypoxia	0.001	0.015	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.002	0.27	-10000	0	-1.2	21	21
alpha5/beta1 Integrin	-0.2	0.29	-10000	0	-0.62	165	165
FGF2	-0.008	0.12	-10000	0	-0.63	17	17
STAT5A (dimer)	0.058	0.22	-10000	0	-0.85	11	11
mol:L-citrulline	0.062	0.18	-10000	0	-0.65	21	21
AGTR1	-0.047	0.18	-10000	0	-0.59	51	51
MAPK14	0.036	0.25	-10000	0	-1.1	21	21
Tie2/SHP2	-0.031	0.17	-10000	0	-1.2	11	11
TEK	0.012	0.2	-10000	0	-1.3	11	11
RPS6KB1	0.059	0.21	-10000	0	-0.85	21	21
Angiotensin II/AT1	-0.033	0.13	-10000	0	-0.44	51	51
Tie2/Ang1/GRB2	0.029	0.26	-10000	0	-1.2	21	21
MAPK3	0.042	0.23	-10000	0	-1	21	21
MAPK1	0.042	0.23	-10000	0	-1	21	21
Tie2/Ang1/GRB7	0.024	0.26	-10000	0	-1.2	21	21
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.03	0.26	-10000	0	-1.2	21	21
PI3K	0.048	0.25	-10000	0	-1	21	21
FES	0.036	0.25	-10000	0	-1.1	21	21
Crk/Dok-R	-0.05	0.22	-10000	0	-1.1	21	21
Tie2/Ang1/ABIN2	0.029	0.26	-10000	0	-1.2	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.059	0.21	-10000	0	-0.79	21	21
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.059	0.21	-10000	0	-0.85	21	21
Tie2/Ang2	0.041	0.25	-10000	0	-1	12	12
Tie2/Ang1	0.026	0.27	-10000	0	-1.2	21	21
FOXO1	0.06	0.22	-10000	0	-0.79	21	21
ELF1	0.017	0.055	-10000	0	-0.59	4	4
ELF2	0.03	0.25	-10000	0	-1.1	21	21
mol:Choline	0.036	0.24	-10000	0	-1.1	21	21
cell migration	-0.088	0.086	-10000	0	-10000	0	0
FYN	0.052	0.22	-10000	0	-0.84	13	13
DOK2	0.008	0.067	-10000	0	-0.75	4	4
negative regulation of cell cycle	0.064	0.18	-10000	0	-0.59	11	11
ETS1	0.014	0.072	-10000	0	-0.79	3	3
PXN	0.069	0.18	-10000	0	-0.7	21	21
ITGB1	0.012	0.036	-10000	0	-0.81	1	1
NOS3	0.059	0.2	-10000	0	-0.74	21	21
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.018	0.17	-10000	0	-0.76	25	25
MAPKKK cascade	0.036	0.24	-10000	0	-1.1	21	21
RASA1	0.011	0.037	-10000	0	-0.58	2	2
Tie2/Ang1/Shc	0.03	0.26	-10000	0	-1.2	21	21
NCK1	0.014	0	-10000	0	-10000	0	0
vasculogenesis	0.063	0.17	-10000	0	-0.58	21	21
mol:Phosphatidic acid	0.036	0.24	-10000	0	-1.1	21	21
mol:Angiotensin II	0	0.007	-10000	0	-10000	0	0
mol:NADP	0.062	0.18	-10000	0	-0.65	21	21
Rac1/GTP	-0.046	0.16	-10000	0	-0.79	21	21
MMP2	-0.027	0.29	-10000	0	-1.1	21	21

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.038	-9999	-0.35	6	6
ARNO/beta Arrestin1-2	-0.02	0.07	-9999	-0.51	1	1
EGFR	-0.015	0.15	-9999	-0.76	19	19
EPHA2	0.006	0.068	-9999	-0.58	7	7
USP6	0.012	0.036	-9999	-0.81	1	1
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.1	0.19	-9999	-0.45	118	118
ARRB2	0.01	0.003	-9999	-10000	0	0
mol:GTP	0.018	0.021	-9999	-0.16	1	1
ARRB1	0.011	0.037	-9999	-0.58	2	2
FBXO8	0.014	0	-9999	-10000	0	0
TSHR	-0.009	0.13	-9999	-0.81	13	13
EGF	-0.1	0.24	-9999	-0.58	101	101
somatostatin receptor activity	0	0	-9999	-0.001	14	14
ARAP2	0.007	0.063	-9999	-0.58	6	6
mol:GDP	-0.013	0.077	-9999	-0.31	14	14
mol:PI-3-4-5-P3	0	0	-9999	-0.001	7	7
ITGA2B	-0.069	0.25	-9999	-0.81	52	52
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.005	0.041	-9999	-0.48	1	1
ADAP1	0.012	0.026	-9999	-0.58	1	1
KIF13B	0.008	0.058	-9999	-0.58	5	5
HGF/MET	-0.027	0.11	-9999	-0.5	28	28
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.025	0.1	-9999	-0.31	15	15
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.085	0.16	-9999	-0.38	118	118
ADRB2	-0.032	0.16	-9999	-0.58	40	40
receptor agonist activity	0	0	-9999	0	17	17
actin filament binding	0	0	-9999	-0.001	14	14
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.017	0.15	-9999	-0.73	21	21
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	8	8
ARF6/GDP	0.04	0.066	-9999	-0.39	2	2
ARF6/GDP/GULP/ACAP1	-0.1	0.15	-9999	-0.44	42	42
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.065	0.17	-9999	-0.5	64	64
ACAP1	-0.005	0.12	-9999	-0.81	12	12
ACAP2	0.012	0.036	-9999	-0.81	1	1
LHCGR/beta Arrestin2	0.002	0.006	-9999	-10000	0	0
EFNA1	0.012	0.036	-9999	-0.81	1	1
HGF	-0.015	0.14	-9999	-0.65	22	22
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.01	0.002	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	10	10
endosomal lumen acidification	0	0	-9999	-0.001	15	15
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.16	0.27	-9999	-0.58	149	149
GNAQ/ARNO	0.015	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	1	1
MET	0.005	0.08	-9999	-0.73	6	6
GNA14	-0.072	0.21	-9999	-0.58	75	75
GNA15	0.011	0.037	-9999	-0.58	2	2
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	10	10
GNA11	0.009	0.052	-9999	-0.58	4	4
LHCGR	0.002	0.005	-9999	-10000	0	0
AGTR1	-0.048	0.18	-9999	-0.59	51	51
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.006	-9999	-10000	0	0
IPCEF1/ARNO	-0.049	0.14	-9999	-0.44	17	17
alphaIIb/beta3 Integrin	-0.083	0.22	-9999	-0.62	70	70

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.12	0.3	-10000	0	-0.81	86	86
Jak2/Leptin Receptor	-0.065	0.1	-10000	0	-0.43	6	6
PTP1B/AKT1	-0.018	0.081	0.23	1	-0.34	3	4
FYN	0.012	0.036	-10000	0	-0.81	1	1
p210 bcr-abl/PTP1B	-0.028	0.09	0.23	2	-0.33	10	12
EGFR	-0.017	0.14	-10000	0	-0.76	19	19
EGF/EGFR	-0.1	0.15	-10000	0	-0.43	49	49
CSF1	0.007	0.063	-10000	0	-0.58	6	6
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.012	0.026	-10000	0	-0.58	1	1
PTP1B/N-cadherin	-0.082	0.19	0.23	1	-0.52	71	72
Insulin Receptor/Insulin	-0.031	0.055	-10000	0	-0.42	2	2
HCK	0.006	0.076	-10000	0	-0.76	5	5
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.019	0.088	0.25	1	-0.37	7	8
EGF	-0.1	0.24	-10000	0	-0.58	101	101
YES1	0.014	0	-10000	0	-10000	0	0
CAV1	-0.043	0.11	0.25	1	-0.37	18	19
TXN	0.01	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.013	0.083	-10000	0	-0.36	2	2
cell migration	0.028	0.09	0.33	10	-0.23	2	12
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.11	0.24	-10000	0	-0.58	104	104
ITGA2B	-0.069	0.25	-10000	0	-0.81	52	52
CSF1R	0.01	0.045	-10000	0	-0.58	3	3
Prolactin Receptor/Prolactin	-0.088	0.18	-10000	0	-0.44	107	107
FGR	0.012	0.036	-10000	0	-0.81	1	1
PTP1B/p130 Cas	-0.019	0.085	0.23	1	-0.34	6	7
Crk/p130 Cas	-0.011	0.081	-10000	0	-0.36	2	2
DOK1	-0.045	0.13	0.24	1	-0.35	38	39
JAK2	-0.057	0.12	-10000	0	-0.37	25	25
Jak2/Leptin Receptor/Leptin	-0.072	0.11	-10000	0	-0.45	6	6
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
PTPN1	-0.028	0.091	0.23	2	-0.33	10	12
LYN	0.012	0.036	-10000	0	-0.81	1	1
CDH2	-0.096	0.28	-10000	0	-0.78	72	72
SRC	0.006	0.037	-10000	0	-10000	0	0
ITGB3	-0.017	0.15	-10000	0	-0.73	21	21
CAT1/PTP1B	-0.11	0.14	0.26	1	-0.43	22	23
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.022	0.054	-10000	0	-0.51	1	1
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.063	0.1	-10000	0	-0.42	3	3
negative regulation of transcription	-0.056	0.12	-10000	0	-0.36	25	25
FCGR2A	-0.028	0.18	-10000	0	-0.81	26	26
FER	0.008	0.037	-10000	0	-0.58	2	2
alphaIIb/beta3 Integrin	-0.083	0.22	-10000	0	-0.62	70	70
BLK	-0.1	0.28	-10000	0	-0.77	75	75
Insulin Receptor/Insulin/Shc	-0.003	0.036	-10000	0	-0.53	2	2
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	0.01	0.045	-10000	0	-0.57	3	3
BCAR1	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.014	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.099	0.14	-10000	0	-0.42	33	33
PRL	-0.004	0.079	-10000	0	-0.8	5	5
SOCS3	0.018	0.061	-10000	0	-1.3	1	1
SPRY2	0.003	0.078	-10000	0	-0.58	9	9
Insulin Receptor/Insulin/IRS1	-0.005	0.045	-10000	0	-0.53	2	2
CSF1/CSF1R	-0.017	0.092	-10000	0	-0.4	7	7
Ras protein signal transduction	0.025	0.029	-10000	0	-10000	0	0
IRS1	0.01	0.045	-10000	0	-0.58	3	3
INS	-0.002	0.05	-10000	0	-0.8	2	2
LEP	-0.094	0.25	-10000	0	-0.67	80	80
STAT5B	-0.035	0.086	0.2	1	-0.32	11	12
STAT5A	-0.035	0.086	0.2	1	-0.32	10	11
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.097	0.22	0.23	1	-0.55	90	91
CSN2	-0.024	0.089	-10000	0	-0.74	2	2
PIK3CA	0.014	0	-10000	0	-10000	0	0
LAT	-0.015	0.087	-10000	0	-0.33	19	19
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.005	0.12	-10000	0	-0.81	12	12
SHC1	0.014	0	-10000	0	-10000	0	0
NOX4	-0.14	0.32	-10000	0	-0.81	96	96

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.002	0.038	-9999	-0.62	2	2
VLDLR	0.002	0.081	-9999	-0.58	10	10
CRKL	0.012	0.036	-9999	-0.81	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.012	0.036	-9999	-0.81	1	1
ITGA3	-0.016	0.15	-9999	-0.8	19	19
RELN/VLDLR/Fyn	-0.079	0.15	-9999	-0.59	5	5
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.006	0.044	-9999	-0.45	2	2
AKT1	-0.032	0.12	-9999	-0.51	6	6
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.016	0.14	-9999	-0.81	16	16
RELN/LRP8/DAB1	-0.091	0.17	-9999	-0.56	28	28
LRPAP1/LRP8	-0.012	0.085	-9999	-0.62	10	10
RELN/LRP8/DAB1/Fyn	-0.085	0.16	-9999	-0.52	29	29
DAB1/alpha3/beta1 Integrin	-0.093	0.16	-9999	-0.66	10	10
long-term memory	-0.15	0.21	-9999	-0.68	33	33
DAB1/LIS1	-0.081	0.15	-9999	-0.68	9	9
DAB1/CRLK/C3G	-0.078	0.15	-9999	-0.66	10	10
PIK3CA	0.014	0	-9999	-10000	0	0
DAB1/NCK2	-0.082	0.15	-9999	-0.66	10	10
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.13	0.28	-9999	-0.68	106	106
CDK5R1	0.01	0.051	-9999	-0.81	2	2
RELN	-0.11	0.24	-9999	-0.58	107	107
PIK3R1	0.011	0.037	-9999	-0.58	2	2
RELN/LRP8/Fyn	-0.083	0.16	-9999	-0.61	13	13
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.16	0.22	-9999	-0.55	87	87
MAPK8	0.006	0.068	-9999	-0.58	7	7
RELN/VLDLR/DAB1	-0.087	0.16	-9999	-0.36	127	127
ITGB1	0.012	0.036	-9999	-0.81	1	1
MAP1B	-0.067	0.19	-9999	-0.55	35	35
RELN/LRP8	-0.082	0.16	-9999	-0.61	12	12
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.088	0.16	-9999	-0.52	33	33
PI3K	-0.002	0.026	-9999	-0.42	2	2
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.023	0.12	-9999	-0.61	20	20
RAP1A	-0.029	0.16	-9999	-0.61	10	10
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.057	-9999	-0.73	3	3
CRLK/C3G	-0.001	0.027	-9999	-0.62	1	1
GRIN2B	-0.004	0.079	-9999	-0.81	5	5
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.012	0.1	-9999	-0.39	7	7
neuron adhesion	-0.03	0.17	-9999	-0.6	9	9
LRP8	-0.002	0.11	-9999	-0.81	10	10
GSK3B	-0.022	0.12	-9999	-0.48	6	6
RELN/VLDLR/DAB1/Fyn	-0.081	0.15	-9999	-0.53	21	21
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.043	0.13	-9999	-0.54	6	6
CDK5	0.014	0	-9999	-10000	0	0
MAPT	-0.24	0.27	-9999	-0.53	241	241
neuron migration	-0.024	0.17	-9999	-0.54	10	10
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.012	0.1	-9999	-0.39	7	7
RELN/VLDLR	-0.079	0.15	-9999	-0.57	14	14

×

ErbB2/ErbB3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.02	0.005	-9999	-10000	0	0
RAS family/GTP	-0.023	0.11	-9999	-0.51	2	2
NFATC4	-0.019	0.12	-9999	-0.52	4	4
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.039	0.14	-9999	-0.59	1	1
JUN	0.001	0.082	-9999	-0.37	5	5
HRAS	0.011	0.036	-9999	-0.81	1	1
DOCK7	-0.031	0.14	-9999	-0.56	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.079	0.17	-9999	-0.47	80	80
AKT1	0.011	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.038	0.074	-9999	-0.31	6	6
mol:GTP	-0.002	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.041	0.15	-9999	-0.66	1	1
RAF1	-0.022	0.12	-9999	-0.5	2	2
ErbB2/ErbB3/neuregulin 2	-0.19	0.17	-9999	-0.62	7	7
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.007	0.083	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.17	0.3	-9999	-0.59	140	140
FOS	-0.12	0.23	-9999	-0.47	88	88
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.039	0.14	-9999	-0.59	1	1
MAPK3	-0.12	0.24	-9999	-0.59	24	24
MAPK1	-0.12	0.24	-9999	-0.55	33	33
JAK2	-0.032	0.14	-9999	-0.56	1	1
NF2	-0.002	0.005	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.026	0.12	-9999	-0.29	81	81
NRG1	-0.11	0.3	-9999	-0.79	82	82
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.017	0.11	-9999	-0.44	2	2
MAPK9	-0.028	0.061	-9999	-10000	0	0
ERBB2	-0.004	0.048	-9999	-0.63	3	3
ERBB3	0.003	0.073	-9999	-0.58	8	8
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	0.008	0.011	-9999	-10000	0	0
STAT3 (dimer)	0.007	0.009	-9999	-10000	0	0
RNF41	0.026	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.04	0.087	-9999	-0.37	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.003	0.041	-9999	-0.54	3	3
CHRNA1	-0.18	0.32	-9999	-0.59	186	186
myelination	-0.007	0.12	-9999	-0.46	4	4
PPP3CB	-0.029	0.13	-9999	-0.51	1	1
KRAS	0.01	0.051	-9999	-0.81	2	2
RAC1-CDC42/GDP	-0.007	0.1	-9999	-0.59	1	1
NRG2	-0.32	0.29	-9999	-0.58	296	296
mol:GDP	-0.025	0.12	-9999	-0.28	81	81
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.03	0.13	-9999	-0.5	1	1
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.032	0.13	-9999	-0.56	1	1
MAP2K1	-0.1	0.2	-9999	-0.52	25	25
heart morphogenesis	-0.039	0.14	-9999	-0.59	1	1
RAS family/GDP	-0.016	0.11	-9999	-0.46	4	4
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.009	-9999	-10000	0	0
CHRNE	0.011	0.029	-9999	-0.23	5	5
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.011	0.003	-9999	-10000	0	0
nervous system development	-0.039	0.14	-9999	-0.59	1	1
CDC42	0.014	0	-9999	-10000	0	0

×

Ephrin A reverse 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
MAPKKK cascade	-0.024	0.096	-9999	-0.4	31	31
EFNA5	-0.014	0.12	-9999	-0.58	24	24
FYN	0	0.099	-9999	-0.56	7	7
neuron projection morphogenesis	-0.024	0.096	-9999	-0.4	31	31
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.024	0.097	-9999	-0.4	31	31
EPHA5	-0.003	0.094	-9999	-0.81	7	7

×

Lissencephaly gene (LIS1) in neuronal migration and development

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	0.002	0.081	-9999	-0.58	10	10
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.082	0.16	-9999	-0.61	12	12
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.045	0.16	-9999	-0.56	12	12
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.016	0.14	-9999	-0.81	16	16
IQGAP1	0.014	0	-9999	-10000	0	0
PLA2G7	-0.31	0.4	-9999	-0.81	204	204
CALM1	0.014	0	-9999	-10000	0	0
DYNLT1	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.012	0.085	-9999	-0.62	10	10
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0.037	-9999	-0.58	2	2
CDK5R1	0.01	0.051	-9999	-0.81	2	2
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	-0.11	0.29	-9999	-0.81	75	75
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.095	0.18	-9999	-0.39	127	127
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.045	0.16	-9999	-0.54	18	18
MAP1B	-0.006	0.041	-9999	-0.3	10	10
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.025	0.14	-9999	-0.69	4	4
RELN	-0.11	0.24	-9999	-0.58	107	107
PAFAH/LIS1	-0.19	0.27	-9999	-0.53	204	204
LIS1/CLIP170	0.027	0.023	-9999	-0.34	2	2
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.064	0.1	-9999	-0.53	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.033	0.13	-9999	-0.56	7	7
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.056	0.17	-9999	-0.59	18	18
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.024	0	-9999	-10000	0	0
PAFAH1B3	0.009	0.062	-9999	-0.81	3	3
PAFAH1B2	0.011	0.037	-9999	-0.58	2	2
MAP1B/LIS1/Dynein heavy chain	0.023	0.03	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.08	0.13	-9999	-0.6	8	8
LRP8	-0.002	0.11	-9999	-0.81	10	10
NDEL1/Katanin 60	-0.045	0.16	-9999	-0.54	18	18
P39/CDK5	-0.094	0.22	-9999	-0.76	18	18
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.033	0.15	-9999	-0.52	12	12
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.001	0.018	-9999	-0.3	2	2
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.078	0.15	-9999	-0.52	20	20
RELN/VLDLR	-0.079	0.15	-9999	-0.57	14	14
CDC42	0	0	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.046	0.18	-9999	-0.4	95	95
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.012	0.036	-9999	-0.81	1	1
STAT1 (dimer)/Cbp/p300	-0.083	0.18	-9999	-0.72	18	18
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.013	0.029	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.07	0.089	-9999	-0.33	10	10
CaM/Ca2+	-0.075	0.15	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.06	0.22	-9999	-0.69	27	27
AKT1	-0.019	0.16	-9999	-10000	0	0
MAP2K1	-0.023	0.16	-9999	-10000	0	0
MAP3K11	-0.036	0.17	-9999	-10000	0	0
IFNGR1	0.008	0.016	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.2	0.23	-9999	-0.62	83	83
Rap1/GTP	-0.057	0.11	-9999	-10000	0	0
CRKL/C3G	-0.001	0.027	-9999	-0.62	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.089	0.17	-9999	-0.43	96	96
CEBPB	0.015	0.15	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.11	0.21	-9999	-0.91	11	11
STAT1	-0.059	0.22	-9999	-0.69	27	27
CALM1	0.014	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.15	0.33	-9999	-0.8	106	106
PIK3CA	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.048	0.21	-9999	-0.76	18	18
CEBPB/PTGES2/Cbp/p300	-0.035	0.067	-9999	-10000	0	0
mol:Ca2+	-0.081	0.16	-9999	-0.4	95	95
MAPK3	-0.004	0.14	-9999	-10000	0	0
STAT1 (dimer)	-0.093	0.12	-9999	-0.46	10	10
MAPK1	-0.004	0.14	-9999	-10000	0	0
JAK2	0.006	0.03	-9999	-0.57	1	1
PIK3R1	0.011	0.037	-9999	-0.58	2	2
JAK1	0.008	0.016	-9999	-10000	0	0
CAMK2D	0.014	0	-9999	-10000	0	0
DAPK1	0.027	0.12	-9999	-0.57	5	5
SMAD7	-0.003	0.073	-9999	-10000	0	0
CBL/CRKL/C3G	-0.068	0.14	-9999	-10000	0	0
PI3K	-0.073	0.14	-9999	-10000	0	0
IFNG	-0.15	0.33	-9999	-0.8	106	106
apoptosis	0.01	0.099	-9999	-0.45	4	4
CAMK2G	0.014	0	-9999	-10000	0	0
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.13	0.26	-9999	-0.58	125	125
CAMK2B	-0.15	0.27	-9999	-0.58	146	146
FRAP1	-0.016	0.15	-9999	-10000	0	0
PRKCD	-0.018	0.16	-9999	-10000	0	0
RAP1B	0.012	0.036	-9999	-0.81	1	1
negative regulation of cell growth	-0.07	0.089	-9999	-0.33	10	10
PTPN2	0.012	0.036	-9999	-0.81	1	1
EP300	0.013	0.026	-9999	-0.57	1	1
IRF1	-0.017	0.18	-9999	-0.51	30	30
STAT1 (dimer)/PIASy	-0.086	0.19	-9999	-0.76	18	18
SOCS1	-0.034	0.16	-9999	-0.65	33	33
mol:GDP	-0.066	0.13	-9999	-10000	0	0
CASP1	-0.003	0.074	-9999	-0.34	1	1
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.038	0.055	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.071	0.14	-9999	-10000	0	0
RAP1/GDP	-0.058	0.11	-9999	-10000	0	0
CBL	-0.037	0.17	-9999	-10000	0	0
MAP3K1	-0.035	0.17	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PIAS4	0.014	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.07	0.089	-9999	-0.33	10	10
PTPN11	-0.047	0.18	-9999	-0.4	95	95
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.036	-9999	-0.81	1	1
EGFR	-0.015	0.15	-9999	-0.76	19	19
EGF/EGFR	-0.075	0.14	-9999	-0.48	25	25
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.07	0.13	-9999	-0.48	17	17
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.007	0.072	-9999	-0.72	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.1	0.24	-9999	-0.58	101	101
EGF/EGFR dimer/SHC	-0.085	0.16	-9999	-0.55	18	18
mol:GDP	-0.069	0.13	-9999	-0.47	17	17
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.008	0.058	-9999	-0.58	5	5
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.064	0.12	-9999	-0.43	18	18
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.065	0.12	-9999	-0.56	3	3
FRAP1	-0.036	0.14	-9999	-0.45	17	17
EGF/EGFR dimer	-0.1	0.19	-9999	-0.45	118	118
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.009	0.067	-9999	-0.48	10	10

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.003	-9999	-10000	0	0
SMARCC1	0.01	0.011	-9999	-10000	0	0
REL	0.006	0.077	-9999	-0.57	9	9
HDAC7	-0.066	0.16	-9999	-0.57	20	20
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.012	0.026	-9999	-0.58	1	1
KAT2B	-0.016	0.13	-9999	-0.58	26	26
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.008	0.1	-9999	-0.44	26	26
FOXO1	0.013	0.001	-9999	-10000	0	0
T-DHT/AR	-0.08	0.17	-9999	-0.61	21	21
MAP2K6	-0.022	0.13	-9999	-0.59	26	26
BRM/BAF57	-0.001	0.018	-9999	-0.42	1	1
MAP2K4	0.008	0.008	-9999	-10000	0	0
SMARCA2	0.01	0.026	-9999	-0.58	1	1
PDE9A	-0.088	0.2	-9999	-1.2	15	15
NCOA2	-0.034	0.16	-9999	-0.58	42	42
CEBPA	0.011	0.045	-9999	-0.58	3	3
EHMT2	0.011	0.005	-9999	-10000	0	0
cell proliferation	-0.058	0.17	-9999	-0.55	11	11
NR0B1	-0.032	0.17	-9999	-0.81	24	24
EGR1	-0.017	0.13	-9999	-0.58	25	25
RXRs/9cRA	-0.042	0.11	-9999	-0.48	8	8
AR/RACK1/Src	-0.036	0.12	-9999	-0.49	13	13
AR/GR	-0.064	0.15	-9999	-0.53	18	18
GNB2L1	0.014	0.001	-9999	-10000	0	0
PKN1	0.01	0.051	-9999	-0.81	2	2
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.008	0.055	-9999	-0.44	7	7
T-DHT/AR/TIF2/CARM1	-0.054	0.16	-9999	-0.68	10	10
SRC	-0.001	0.095	-9999	-0.6	2	2
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.28	0.45	-9999	-1.2	95	95
APPBP2	0.008	0.008	-9999	-10000	0	0
TRIM24	0.01	0.026	-9999	-0.58	1	1
T-DHT/AR/TIP60	-0.036	0.13	-9999	-0.52	18	18
TMPRSS2	-0.51	0.55	-9999	-1.1	244	244
RXRG	-0.064	0.2	-9999	-0.6	64	64
mol:9cRA	-0.001	0.003	-9999	-10000	0	0
RXRA	0.013	0.001	-9999	-10000	0	0
RXRB	0.013	0.001	-9999	-10000	0	0
CARM1	0.014	0.002	-9999	-10000	0	0
NR2C2	0.005	0.068	-9999	-0.58	7	7
KLK2	-0.037	0.16	-9999	-0.64	18	18
AR	-0.08	0.17	-9999	-0.48	32	32
SENP1	0.013	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.018	0.012	-9999	-10000	0	0
SRY	-0.034	0.16	-9999	-0.58	39	39
GATA2	0.009	0.057	-9999	-0.73	3	3
MYST2	0.013	0.026	-9999	-0.58	1	1
HOXB13	-0.31	0.4	-9999	-0.82	197	197
T-DHT/AR/RACK1/Src	-0.028	0.12	-9999	-0.49	18	18
positive regulation of transcription	0.009	0.057	-9999	-0.73	3	3
DNAJA1	0.008	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.004	-9999	-10000	0	0
NCOA1	0.017	0.008	-9999	-10000	0	0
SPDEF	-0.15	0.28	-9999	-0.61	135	135
T-DHT/AR/TIF2	-0.033	0.15	-9999	-0.6	15	15
T-DHT/AR/Hsp90	-0.038	0.13	-9999	-0.52	18	18
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.002	-9999	-10000	0	0
mol:T-DHT	-0.012	0.1	-9999	-0.65	2	2
SIRT1	0.012	0.026	-9999	-0.58	1	1
ZMIZ2	0.018	0.011	-9999	-10000	0	0
POU2F1	0.016	0.022	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.075	0.15	-9999	-0.54	33	33
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.011	0.005	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.003	0.096	-9999	-0.64	11	11
PDGF/PDGFRA/CRKL	-0.011	0.072	-9999	-0.47	12	12
positive regulation of JUN kinase activity	-0.007	0.049	-9999	-0.45	3	3
CRKL	0.012	0.036	-9999	-0.81	1	1
PDGF/PDGFRA/Caveolin-3	-0.1	0.19	-9999	-0.44	121	121
AP1	-0.13	0.32	-9999	-0.95	67	67
mol:IP3	0.01	0.075	-9999	-0.47	11	11
PLCG1	0.01	0.075	-9999	-0.47	11	11
PDGF/PDGFRA/alphaV Integrin	-0.015	0.092	-9999	-0.53	15	15
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.075	-9999	-0.47	11	11
CAV3	-0.12	0.24	-9999	-0.58	113	113
CAV1	-0.046	0.21	-9999	-0.81	38	38
SHC/Grb2/SOS1	-0.007	0.05	-9999	-0.46	3	3
PDGF/PDGFRA/Shf	-0.017	0.091	-9999	-0.48	18	18
FOS	-0.084	0.33	-9999	-0.94	67	67
JUN	-0.008	0.02	-9999	-10000	0	0
oligodendrocyte development	-0.015	0.091	-9999	-0.52	15	15
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
mol:DAG	0.01	0.075	-9999	-0.47	11	11
PDGF/PDGFRA	-0.003	0.096	-9999	-0.64	11	11
actin cytoskeleton reorganization	-0.011	0.072	-9999	-0.45	13	13
SRF	0.025	0.009	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
PI3K	-0.009	0.06	-9999	-0.47	4	4
PDGF/PDGFRA/Crk/C3G	-0.008	0.056	-9999	-0.51	3	3
JAK1	0.013	0.071	-9999	-0.46	11	11
ELK1/SRF	0.031	0.059	-9999	-0.42	4	4
SHB	0.011	0.037	-9999	-0.58	2	2
SHF	0.003	0.077	-9999	-0.58	9	9
CSNK2A1	0.008	0.02	-9999	-10000	0	0
GO:0007205	0.01	0.076	-9999	-0.48	11	11
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.007	0.049	-9999	-0.45	3	3
PDGF/PDGFRA/SHB	-0.011	0.072	-9999	-0.45	13	13
PDGF/PDGFRA/Caveolin-1	-0.056	0.18	-9999	-0.59	49	49
ITGAV	0.006	0.076	-9999	-0.76	5	5
ELK1	0.013	0.077	-9999	-0.43	12	12
PIK3CA	0.014	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.01	0.067	-9999	-0.46	11	11
JAK-STAT cascade	0.013	0.07	-9999	-0.46	11	11
cell proliferation	-0.017	0.091	-9999	-0.48	18	18

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.28	-9999	-0.72	77	77
MKNK1	0.014	0	-9999	-10000	0	0
MAPK14	-0.043	0.12	-9999	-0.4	13	13
ATF2/c-Jun	-0.01	0.095	-9999	-10000	0	0
MAPK11	-0.043	0.12	-9999	-0.4	13	13
MITF	-0.051	0.17	-9999	-0.57	23	23
MAPKAPK5	-0.037	0.14	-9999	-0.48	13	13
KRT8	-0.12	0.23	-9999	-0.63	52	52
MAPKAPK3	0.014	0	-9999	-10000	0	0
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.063	0.18	-9999	-0.64	13	13
CEBPB	-0.037	0.14	-9999	-0.48	13	13
SLC9A1	-0.037	0.14	-9999	-0.48	13	13
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.031	0.14	-9999	-0.47	13	13
p38alpha-beta/MNK1	-0.036	0.15	-9999	-0.52	13	13
JUN	-0.009	0.094	-9999	-10000	0	0
PPARGC1A	-0.17	0.25	-9999	-0.69	66	66
USF1	-0.037	0.14	-9999	-0.48	13	13
RAB5/GDP/GDI1	-0.05	0.085	-9999	-0.4	2	2
NOS2	-0.11	0.3	-9999	-0.73	89	89
DDIT3	-0.047	0.16	-9999	-0.52	18	18
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.019	0.12	-9999	-0.39	13	13
p38alpha-beta/HBP1	-0.036	0.15	-9999	-0.52	13	13
CREB1	-0.033	0.15	-9999	-0.47	13	13
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.024	0.13	-9999	-0.46	13	13
RPS6KA4	-0.037	0.14	-9999	-0.48	13	13
PLA2G4A	-0.045	0.16	-9999	-0.54	20	20
GDI1	-0.037	0.14	-9999	-0.48	13	13
TP53	-0.052	0.18	-9999	-0.59	15	15
RPS6KA5	-0.039	0.15	-9999	-0.48	13	13
ESR1	-0.057	0.17	-9999	-0.55	24	24
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.045	0.15	-9999	-0.5	15	15
MEF2A	-0.037	0.14	-9999	-0.48	13	13
EIF4EBP1	-0.035	0.15	-9999	-0.47	13	13
KRT19	-0.17	0.22	-9999	-0.64	47	47
ELK4	-0.037	0.14	-9999	-0.48	13	13
ATF6	-0.037	0.14	-9999	-0.48	13	13
ATF1	-0.033	0.15	-9999	-0.47	13	13
p38alpha-beta/MAPKAPK2	-0.036	0.15	-9999	-0.52	13	13
p38alpha-beta/MAPKAPK3	-0.036	0.15	-9999	-0.52	13	13

×

Signaling events mediated by HDAC Class III

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
EP300	0.012	0.026	-10000	0	-0.58	1	1
HDAC4	0.014	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.014	0.14	0.61	29	-10000	0	29
CDKN1A	0.001	0.012	-10000	0	-10000	0	0
KAT2B	-0.016	0.13	-10000	0	-0.58	26	26
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.001	0.02	0.44	1	-10000	0	1
FOXO1	0.014	0	-10000	0	-10000	0	0
FOXO4	0.022	0.024	-10000	0	-0.29	3	3
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	-0.002	0.087	-10000	0	-0.81	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.079	0.19	-10000	0	-0.44	111	111
PPARGC1A	-0.19	0.28	-10000	0	-0.58	181	181
FHL2	0.011	0.037	-10000	0	-0.58	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.018	-10000	0	-0.42	1	1
HIST2H4A	-0.014	0.15	-10000	0	-0.61	29	29
SIRT1/FOXO3a	0	0.02	0.29	1	-0.35	1	2
SIRT1	-0.001	0.025	-10000	0	-0.58	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.015	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.012	0.053	-10000	0	-10000	0	0
apoptosis	0.001	0.015	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.12	0.17	-10000	0	-0.36	181	181
p53/SIRT1	-0.004	0.041	-10000	0	-0.42	5	5
SIRT1/FOXO4	-0.002	0.024	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.002	0.024	-10000	0	-10000	0	0
HIST1H1E	0.009	0.067	-10000	0	-0.28	26	26
SIRT1/p300	-0.002	0.026	-10000	0	-0.42	2	2
muscle cell differentiation	0.078	0.15	0.6	8	-10000	0	8
TP53	-0.004	0.05	-10000	0	-0.58	4	4
KU70/SIRT1/BAX	-0.001	0.015	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.014	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.008	0.069	-10000	0	-0.59	7	7
ACSS2	0.021	0.019	-10000	0	-0.42	1	1
SIRT1/PCAF/MYOD	-0.079	0.15	-10000	0	-0.6	8	8

×

TRAIL 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
TNFSF10	0	0.1	-10000	0	-0.78	9	9
positive regulation of NF-kappaB transcription factor activity	-0.03	0.13	-10000	0	-0.59	26	26
MAP2K4	0.011	0.096	-10000	0	-10000	0	0
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.014	0	-10000	0	-10000	0	0
TNFRSF10A	0.011	0.037	-10000	0	-0.58	2	2
SMPD1	0.016	0.035	-10000	0	-0.25	8	8
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.012	0.14	-10000	0	-0.78	17	17
TRAIL/TRAILR2	-0.01	0.078	-10000	0	-0.6	9	9
TRAIL/TRAILR3	-0.027	0.12	-10000	0	-0.59	24	24
TRAIL/TRAILR1	-0.012	0.082	-10000	0	-0.56	11	11
TRAIL/TRAILR4	-0.03	0.13	-10000	0	-0.59	26	26
TRAIL/TRAILR1/DAP3/GTP	-0.009	0.065	-10000	0	-0.49	8	8
IKK complex	-0.024	0.06	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.081	-10000	0	-0.59	9	9
MAP3K1	0.003	0.1	-10000	0	-10000	0	0
TRAILR4 (trimer)	-0.012	0.14	-10000	0	-0.78	17	17
TRADD	0.014	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.011	0.036	-10000	0	-0.58	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.004	0.1	-10000	0	-10000	0	0
CFLAR	0.014	0	-10000	0	-10000	0	0
MAPK1	0.014	0.081	-10000	0	-0.59	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.061	0.15	-10000	0	-0.45	68	68
mol:ceramide	0.016	0.035	-10000	0	-0.25	8	8
FADD	-0.081	0.26	-10000	0	-0.81	60	60
MAPK8	0.014	0.1	-10000	0	-0.5	3	3
TRAF2	0.004	0.088	-10000	0	-0.81	6	6
TRAILR3 (trimer)	-0.009	0.13	-10000	0	-0.78	15	15
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.072	0.18	-10000	0	-0.53	68	68
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.05	0.16	0.28	14	-0.44	65	79
JNK cascade	-0.03	0.13	-10000	0	-0.59	26	26
TRAIL (trimer)	0	0.1	-10000	0	-0.78	9	9
TNFRSF10C	-0.009	0.13	-10000	0	-0.78	15	15
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.062	0.16	-10000	0	-0.46	68	68
TRAIL/TRAILR2/FADD	-0.07	0.18	-10000	0	-0.53	68	68
cell death	0.016	0.035	-10000	0	-0.25	8	8
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.1	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.014	0	-10000	0	-10000	0	0
CASP8	-0.001	0.021	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.06	0.15	-10000	0	-0.45	68	68

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.14	0.3	-9999	-0.7	88	88
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.039	0.15	-9999	-0.42	67	67
IFNAR2	0.012	0.007	-9999	-10000	0	0
AKT1	0	0.063	-9999	-0.34	2	2
ER alpha/Oestrogen	-0.02	0.12	-9999	-0.52	28	28
NFX1/SIN3/HDAC complex	0.039	0.027	-9999	-10000	0	0
EGF	-0.1	0.24	-9999	-0.58	101	101
SMG5	0.014	0	-9999	-10000	0	0
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.018	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.16	0.26	-9999	-0.66	85	85
SAP18	0.012	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.16	0.33	-9999	-0.81	109	109
WRN	0.014	0	-9999	-10000	0	0
SP1	0.013	0.007	-9999	-10000	0	0
SP3	0.011	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.14	0.23	-9999	-0.66	38	38
Mad/Max	0.013	0.044	-9999	-0.42	5	5
TERT	-0.15	0.31	-9999	-0.72	88	88
CCND1	-0.13	0.29	-9999	-0.73	45	45
MAX	0.011	0.006	-9999	-10000	0	0
RBBP7	0.012	0.004	-9999	-10000	0	0
RBBP4	0.011	0.026	-9999	-0.58	1	1
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.012	0.004	-9999	-10000	0	0
Telomerase/911	0.024	0.042	-9999	-10000	0	0
CDKN1B	-0.078	0.22	-9999	-0.52	106	106
RAD1	0.014	0	-9999	-10000	0	0
XRCC5	0.014	0	-9999	-10000	0	0
XRCC6	0.014	0	-9999	-10000	0	0
SAP30	0.01	0.036	-9999	-0.81	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.011	0.006	-9999	-10000	0	0
JUN	0.012	0.006	-9999	-10000	0	0
E6	-0.002	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.006	-9999	-10000	0	0
FOS	-0.065	0.2	-9999	-0.58	67	67
IFN-gamma/IRF1	-0.12	0.24	-9999	-0.61	106	106
PARP2	0.014	0	-9999	-10000	0	0
BLM	0.01	0.051	-9999	-0.81	2	2
Telomerase	-0.007	0.1	-9999	-0.43	13	13
IRF1	0.015	0.008	-9999	-10000	0	0
ESR1	-0.025	0.16	-9999	-0.68	28	28
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.016	-9999	-0.37	1	1
ubiquitin-dependent protein catabolic process	0.043	0.029	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.044	0.029	-9999	-10000	0	0
HDAC1	0.012	0.004	-9999	-10000	0	0
HDAC2	0.013	0.007	-9999	-10000	0	0
ATM	-0.001	0.019	-9999	-0.44	1	1
SMAD3	0.021	0.052	-9999	-0.56	4	4
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.006	0.058	-9999	-0.58	5	5
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.012	0.036	-9999	-0.81	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.25	-9999	-0.68	45	45
NR2F2	0.015	0.037	-9999	-0.79	1	1
MAPK3	0.013	0.029	-9999	-0.61	1	1
MAPK1	0.013	0.029	-9999	-0.61	1	1
TGFB1/TGF beta receptor Type II	0.01	0.062	-9999	-0.8	3	3
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.019	-9999	-0.44	1	1
NBN	0.014	0	-9999	-10000	0	0
EGFR	-0.016	0.15	-9999	-0.76	19	19
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.095	0.2	-9999	-0.45	118	118
MYC	0.011	0.006	-9999	-10000	0	0
IL2	0.001	0.038	-9999	-0.8	1	1
KU	0	0	-9999	-10000	0	0
RAD50	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
TGFB1	0.01	0.062	-9999	-0.8	3	3
TRF2/BLM	-0.002	0.036	-9999	-0.58	2	2
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.15	0.26	-9999	-0.68	68	68
SP1/HDAC2	0.019	0.015	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.14	0.23	-9999	-0.67	36	36
Smad3/Myc	0.026	0.045	-9999	-0.48	4	4
911 complex	-0.001	0.023	-9999	-0.53	1	1
IFNG	-0.15	0.33	-9999	-0.8	106	106
Telomerase/PinX1	-0.14	0.23	-9999	-0.68	32	32
Telomerase/AKT1/mTOR/p70S6K	0	0.075	-9999	-10000	0	0
SIN3B	0.012	0.004	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.14	0.23	-9999	-0.67	34	34
response to DNA damage stimulus	0.003	0.006	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.23	-9999	-0.66	38	38
E2F1	-0.05	0.22	-9999	-0.82	39	39
ZNFX1	0.012	0.004	-9999	-10000	0	0
PIF1	-0.035	0.19	-9999	-0.81	31	31
NCL	0.014	0	-9999	-10000	0	0
DKC1	0.014	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Noncanonical Wnt signaling pathway

Figure S66. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S66. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.056	0.19	-9999	-0.58	61	61
GNB1/GNG2	-0.059	0.13	-9999	-0.65	11	11
mol:DAG	-0.009	0.13	-9999	-0.6	10	10
PLCG1	-0.01	0.14	-9999	-0.62	10	10
YES1	-0.028	0.15	-9999	-0.68	11	11
FZD3	0.006	0.068	-9999	-0.58	7	7
FZD6	0.009	0.057	-9999	-0.73	3	3
G protein	-0.011	0.14	-9999	-0.61	11	11
MAP3K7	-0.057	0.16	-9999	-0.66	8	8
mol:Ca2+	-0.008	0.13	-9999	-0.57	10	10
mol:IP3	-0.009	0.13	-9999	-0.6	10	10
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.07	0.18	-9999	-0.52	32	32
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.039	0.16	-9999	-0.73	11	11
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.028	0.15	-9999	-0.68	11	11
GO:0007205	-0.008	0.13	-9999	-0.58	10	10
WNT6	-0.052	0.22	-9999	-0.76	44	44
WNT4	-0.008	0.12	-9999	-0.63	17	17
NFAT1/CK1 alpha	-0.081	0.15	-9999	-0.57	26	26
GNG2	0.014	0	-9999	-10000	0	0
WNT5A	0.005	0.072	-9999	-0.61	7	7
WNT11	-0.075	0.24	-9999	-0.74	61	61
CDC42	-0.018	0.14	-9999	-0.64	11	11

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.012	0.036	-9999	-0.81	1	1
LAT2	-0.054	0.14	-9999	-0.49	20	20
AP1	-0.091	0.12	-9999	-0.53	13	13
mol:PIP3	-0.07	0.19	-9999	-0.55	27	27
IKBKB	-0.026	0.11	-9999	-0.34	6	6
AKT1	-0.054	0.16	-9999	-0.64	6	6
IKBKG	-0.026	0.11	-9999	-0.34	6	6
MS4A2	-0.012	0.12	-9999	-0.6	20	20
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
MAP3K1	-0.018	0.12	-9999	-0.48	5	5
mol:Ca2+	-0.05	0.15	-9999	-0.4	27	27
LYN	0.012	0.037	-9999	-0.82	1	1
CBLB	-0.052	0.14	-9999	-0.48	19	19
SHC1	0.014	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.018	0.079	-9999	-0.8	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.011	0.037	-9999	-0.58	2	2
PLD2	-0.091	0.18	-9999	-0.63	17	17
PTPN13	-0.048	0.14	-9999	-0.5	17	17
PTPN11	0.009	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.023	0.13	-9999	-0.42	3	3
SYK	0.01	0.046	-9999	-0.59	3	3
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.16	-9999	-0.56	31	31
LAT	-0.064	0.16	-9999	-0.53	31	31
PAK2	-0.029	0.13	-9999	-0.53	6	6
NFATC2	-0.12	0.23	-9999	-0.7	61	61
HRAS	-0.04	0.14	-9999	-0.46	24	24
GAB2	0.01	0.045	-9999	-0.58	3	3
PLA2G1B	0.035	0.019	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.21	-9999	-0.67	25	25
Antigen/IgE/Fc epsilon R1	-0.14	0.19	-9999	-0.62	26	26
mol:GDP	-0.046	0.14	-9999	-0.48	24	24
JUN	0.014	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
FOS	-0.063	0.2	-9999	-0.58	67	67
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.087	0.13	-9999	-0.48	24	24
CHUK	-0.026	0.11	-9999	-0.34	6	6
KLRG1	-0.06	0.14	-9999	-0.47	25	25
VAV1	-0.058	0.14	-9999	-0.49	24	24
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.052	0.14	-9999	-0.48	19	19
negative regulation of mast cell degranulation	-0.049	0.14	-9999	-0.5	13	13
BTK	-0.05	0.14	-9999	-0.48	20	20
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.085	0.18	-9999	-0.63	24	24
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.67	8	8
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.072	0.16	-9999	-0.59	19	19
RAF1	0.023	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.18	-9999	-0.62	23	23
FCER1G	-0.007	0.12	-9999	-0.81	12	12
FCER1A	-0.2	0.29	-9999	-0.58	186	186
Antigen/IgE/Fc epsilon R1/Fyn	-0.13	0.18	-9999	-0.6	25	25
MAPK3	0.034	0.019	-9999	-10000	0	0
MAPK1	0.034	0.019	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0	0.088	-9999	-0.65	7	7
DUSP1	-0.017	0.13	-9999	-0.58	27	27
NF-kappa-B/RelA	-0.037	0.048	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.051	0.14	-9999	-0.49	16	16
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.071	0.11	-9999	-0.54	7	7
FER	-0.053	0.14	-9999	-0.48	21	21
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.032	0.077	-9999	-0.41	17	17
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.046	0.15	-9999	-0.48	24	24
cytokine secretion	-0.027	0.035	-9999	-10000	0	0
SPHK1	-0.065	0.16	-9999	-0.52	33	33
PTK2	-0.053	0.14	-9999	-0.52	16	16
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.16	-9999	-0.56	24	24
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.062	0.18	-9999	-0.52	21	21
MAP2K2	0.03	0.02	-9999	-10000	0	0
MAP2K1	0.03	0.02	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.082	0.12	-9999	-0.44	25	25
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.14	0.19	-9999	-0.62	30	30
mol:Choline	-0.089	0.18	-9999	-0.62	17	17
SHC/Grb2/SOS1	-0.07	0.11	-9999	-0.45	19	19
FYN	0.012	0.036	-9999	-0.81	1	1
DOK1	0.012	0.036	-9999	-0.81	1	1
PXN	-0.042	0.13	-9999	-0.48	15	15
HCLS1	-0.055	0.14	-9999	-0.49	23	23
PRKCB	-0.049	0.15	-9999	-0.41	22	22
FCGR2B	0.006	0.068	-9999	-0.58	7	7
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.05	0.14	-9999	-0.51	13	13
LCP2	0.008	0.062	-9999	-0.81	3	3
PLA2G4A	-0.07	0.17	-9999	-0.52	36	36
RASA1	0.011	0.037	-9999	-0.58	2	2
mol:Phosphatidic acid	-0.089	0.18	-9999	-0.62	17	17
IKK complex	-0.004	0.091	-9999	-0.28	2	2
WIPF1	0.007	0.072	-9999	-0.81	4	4

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.076	-9999	-0.58	9	9
PDGFRB	-0.12	0.3	-9999	-0.8	86	86
SPHK1	-0.023	0.055	-9999	-0.32	15	15
mol:S1P	-0.028	0.066	-9999	-0.4	9	9
S1P1/S1P/Gi	-0.011	0.13	-9999	-0.52	9	9
GNAO1	0.006	0.068	-9999	-0.76	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.057	0.19	-9999	-0.58	17	17
PLCG1	-0.01	0.13	-9999	-0.49	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.12	0.3	-9999	-0.8	86	86
GNAI2	0.012	0.005	-9999	-10000	0	0
GNAI3	0.012	0.005	-9999	-10000	0	0
GNAI1	0.011	0.027	-9999	-0.59	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.009	0.069	-9999	-0.5	9	9
S1P1/S1P	-0.038	0.08	-9999	-0.41	14	14
negative regulation of cAMP metabolic process	-0.011	0.13	-9999	-0.5	9	9
MAPK3	-0.018	0.17	-9999	-0.51	23	23
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.011	0.037	-9999	-0.58	2	2
PLCB2	-0.001	0.096	-9999	-0.43	9	9
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.032	0.067	-9999	-0.36	12	12
receptor internalization	-0.037	0.075	-9999	-0.39	14	14
PTGS2	-0.047	0.25	-9999	-0.61	77	77
Rac1/GTP	-0.032	0.067	-9999	-0.36	12	12
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	0.002	0.095	-9999	-0.81	7	7
negative regulation of T cell proliferation	-0.011	0.13	-9999	-0.5	9	9
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.015	0.14	-9999	-0.74	19	19
MAPK1	-0.018	0.17	-9999	-0.51	23	23
S1P1/S1P/PDGFB-D/PDGFRB	-0.053	0.18	-9999	-0.5	22	22
ABCC1	0.006	0.072	-9999	-0.81	4	4

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.031	0.11	-10000	0	-0.47	25	25
ER alpha/Gai/GDP/Gbeta gamma	0.021	0.094	-10000	0	-0.46	4	4
AKT1	0.008	0.14	-10000	0	-0.75	15	15
PIK3CA	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.006	0.14	-10000	0	-0.76	15	15
mol:Ca2+	-0.028	0.16	-10000	0	-0.6	8	8
IGF1R	0.012	0.036	-10000	0	-0.81	1	1
E2/ER alpha (dimer)/Striatin	-0.038	0.12	-10000	0	-0.41	48	48
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	-0.009	0.14	0.72	15	-10000	0	15
RhoA/GTP	-0.019	0.079	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.025	0.085	-10000	0	-0.51	3	3
regulation of stress fiber formation	-0.033	0.081	0.5	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.037	0.13	-10000	0	-0.48	40	40
KRAS	0.01	0.051	-10000	0	-0.81	2	2
G13/GTP	-0.022	0.093	-10000	0	-0.4	28	28
pseudopodium formation	0.033	0.081	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/PELP1	-0.024	0.1	-10000	0	-0.44	28	28
GRB2	0.014	0	-10000	0	-10000	0	0
GNG2	0.014	0	-10000	0	-10000	0	0
GNAO1	0.008	0.067	-10000	0	-0.75	4	4
HRAS	0.012	0.036	-10000	0	-0.81	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.021	0.11	-10000	0	-0.47	16	16
E2/ER beta (dimer)	-0.015	0.096	-10000	0	-0.61	13	13
mol:GDP	-0.03	0.1	-10000	0	-0.38	39	39
mol:NADP	0.021	0.11	-10000	0	-0.47	16	16
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
mol:IP3	-0.03	0.16	-10000	0	-0.63	8	8
IGF-1R heterotetramer	0.012	0.036	-10000	0	-0.81	1	1
PLCB1	-0.036	0.16	-10000	0	-0.41	77	77
PLCB2	-0.037	0.16	-10000	0	-0.4	79	79
IGF1	-0.086	0.22	-10000	0	-0.59	86	86
mol:L-citrulline	0.021	0.11	-10000	0	-0.47	16	16
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.012	0.057	-10000	0	-0.56	2	2
JNK cascade	-0.015	0.095	-10000	0	-0.61	13	13
BCAR1	0.014	0	-10000	0	-10000	0	0
ESR2	-0.007	0.13	-10000	0	-0.79	13	13
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.024	0.16	-10000	0	-0.68	28	28
Gq family/GDP/Gbeta gamma	0.001	0.11	-10000	0	-0.62	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.028	0.063	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.025	0.085	-10000	0	-0.51	3	3
GNAZ	-0.014	0.14	-10000	0	-0.74	19	19
E2/ER alpha (dimer)	-0.028	0.12	-10000	0	-0.52	28	28
STRN	-0.01	0.12	-10000	0	-0.58	21	21
GNAL	-0.061	0.2	-10000	0	-0.58	66	66
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.006	0.085	-10000	0	-0.52	13	13
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.026	-10000	0	-0.58	1	1
HBEGF	-0.16	0.16	-10000	0	-0.45	82	82
cAMP biosynthetic process	-0.065	0.14	-10000	0	-0.48	30	30
SRC	0.028	0.09	-10000	0	-0.47	3	3
PI3K	-0.002	0.026	-10000	0	-0.42	2	2
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.027	0.091	-10000	0	-0.7	1	1
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.052	0.11	-10000	0	-0.51	9	9
Gs family/GTP	-0.066	0.14	-10000	0	-0.49	30	30
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.037	-10000	0	-0.49	3	3
vasodilation	0.021	0.11	-10000	0	-0.45	16	16
mol:DAG	-0.03	0.16	-10000	0	-0.63	8	8
Gs family/GDP/Gbeta gamma	-0.051	0.11	-10000	0	-0.56	7	7
MSN	0.033	0.087	-10000	0	-0.56	1	1
Gq family/GTP	-0.073	0.16	-10000	0	-0.43	76	76
mol:PI-3-4-5-P3	0.007	0.14	-10000	0	-0.73	15	15
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.021	0.11	0.45	16	-10000	0	16
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.028	0.097	-10000	0	-0.39	15	15
NOS3	0.02	0.12	-10000	0	-0.5	16	16
GNA11	0.009	0.052	-10000	0	-0.58	4	4
MAPKKK cascade	0.02	0.14	-10000	0	-0.56	16	16
E2/ER alpha (dimer)/PELP1/Src	-0.026	0.09	-10000	0	-0.53	3	3
ruffle organization	0.033	0.081	-10000	0	-0.5	1	1
ROCK2	0.026	0.093	-10000	0	-0.63	1	1
GNA14	-0.072	0.21	-10000	0	-0.58	75	75
GNA15	0.011	0.037	-10000	0	-0.58	2	2
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.29	0.21	-10000	0	-0.57	46	46
MMP2	-0.022	0.17	-10000	0	-0.55	6	6

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.031	0.041	-9999	-0.57	2	2
VEGFR1 homodimer/NRP1	0.022	0.033	-9999	-0.62	1	1
mol:DAG	-0.05	0.2	-9999	-0.48	93	93
VEGFR1 homodimer/NRP1/VEGFR 121	-0.008	0.063	-9999	-0.5	8	8
CaM/Ca2+	-0.041	0.19	-9999	-0.62	2	2
HIF1A	0.02	0.029	-9999	-0.56	1	1
GAB1	0.014	0	-9999	-10000	0	0
AKT1	-0.016	0.17	-9999	-0.75	3	3
PLCG1	-0.051	0.2	-9999	-0.48	93	93
NOS3	-0.012	0.17	-9999	-0.72	1	1
CBL	0.014	0	-9999	-10000	0	0
mol:NO	-0.011	0.16	-9999	-0.53	3	3
FLT1	0.03	0.038	-9999	-0.71	1	1
PGF	-0.13	0.31	-9999	-0.81	92	92
VEGFR1 homodimer/NRP2/VEGFR121	-0.01	0.068	-9999	-0.49	10	10
CALM1	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
eNOS/Hsp90	-0.003	0.16	-9999	-0.66	1	1
endothelial cell proliferation	-0.027	0.17	-9999	-0.71	1	1
mol:Ca2+	-0.05	0.2	-9999	-0.47	93	93
MAPK3	-0.03	0.18	-9999	-0.57	2	2
MAPK1	-0.03	0.18	-9999	-0.57	2	2
PIK3R1	0.011	0.037	-9999	-0.58	2	2
PLGF homodimer	-0.13	0.31	-9999	-0.81	92	92
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.046	0.21	-9999	-0.81	38	38
VEGFA homodimer	0.002	0.094	-9999	-0.81	7	7
VEGFR1 homodimer/VEGFA homodimer	0.025	0.072	-9999	-0.54	8	8
platelet activating factor biosynthetic process	-0.021	0.17	-9999	-0.64	1	1
PI3K	-0.081	0.18	-9999	-0.68	4	4
PRKCA	-0.04	0.19	-9999	-0.61	2	2
PRKCB	-0.045	0.19	-9999	-0.61	2	2
VEGFR1 homodimer/PLGF homodimer	-0.067	0.22	-9999	-0.53	93	93
VEGFA	0.002	0.095	-9999	-0.81	7	7
VEGFB	0.012	0.036	-9999	-0.81	1	1
mol:IP3	-0.05	0.2	-9999	-0.48	93	93
RASA1	0.039	0.047	-9999	-0.55	3	3
NRP2	0.01	0.051	-9999	-0.81	2	2
VEGFR1 homodimer	0.03	0.037	-9999	-0.71	1	1
VEGFB homodimer	0.012	0.036	-9999	-0.81	1	1
NCK1	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.035	0.2	-9999	-0.73	10	10
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.08	0.17	-9999	-0.67	4	4
mol:L-citrulline	-0.011	0.16	-9999	-0.53	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.008	0.057	-9999	-0.53	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.008	0.062	-9999	-0.49	8	8
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.076	0.16	-9999	-0.65	4	4
PDPK1	-0.032	0.18	-9999	-0.77	3	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.008	0.062	-9999	-0.49	8	8
mol:NADP	-0.011	0.16	-9999	-0.53	3	3
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.007	0.057	-9999	-0.52	1	1
VEGFR1 homodimer/NRP2	0.03	0.048	-9999	-0.56	3	3

×

EPO signaling 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
BCL2L1	0.024	0.13	-10000	0	-0.54	3	3
CRKL	-0.006	0.15	-10000	0	-0.56	3	3
mol:DAG	0.006	0.14	-10000	0	-0.61	3	3
HRAS	0.024	0.13	-10000	0	-0.59	2	2
MAPK8	-0.029	0.18	-10000	0	-0.47	67	67
RAP1A	-0.005	0.15	-10000	0	-0.63	2	2
GAB1	-0.005	0.15	-10000	0	-0.63	2	2
MAPK14	-0.024	0.17	-10000	0	-0.46	67	67
EPO	-0.075	0.26	-10000	0	-0.8	57	57
PLCG1	0.005	0.14	-10000	0	-0.63	3	3
EPOR/TRPC2/IP3 Receptors	-0.005	0.12	-10000	0	-0.8	11	11
RAPGEF1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.064	0.17	-10000	0	-0.51	67	67
GAB1/SHC/GRB2/SOS1	-0.042	0.11	-10000	0	-0.66	1	1
EPO/EPOR (dimer)	-0.057	0.22	-10000	0	-0.62	67	67
IRS2	-0.006	0.15	-10000	0	-0.63	2	2
STAT1	-0.009	0.16	-10000	0	-0.65	5	5
STAT5B	0.01	0.14	-10000	0	-0.64	3	3
cell proliferation	-0.018	0.17	-10000	0	-0.72	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.042	0.11	-10000	0	-0.63	2	2
TEC	-0.019	0.17	-10000	0	-0.68	9	9
SOCS3	0.012	0.026	-10000	0	-0.58	1	1
STAT1 (dimer)	-0.008	0.16	-10000	0	-0.63	5	5
JAK2	0.01	0.029	-10000	0	-0.57	1	1
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
EPO/EPOR (dimer)/JAK2	-0.002	0.16	-10000	0	-0.47	8	8
EPO/EPOR	-0.057	0.22	-10000	0	-0.62	67	67
LYN	0.014	0.036	-10000	0	-0.81	1	1
TEC/VAV2	-0.025	0.19	-10000	0	-0.74	13	13
elevation of cytosolic calcium ion concentration	-0.005	0.12	-10000	0	-0.8	11	11
SHC1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.032	0.19	-10000	0	-0.52	67	67
mol:IP3	0.006	0.14	-10000	0	-0.61	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.047	0.12	-10000	0	-0.7	2	2
SH2B3	0.009	0.038	-10000	0	-0.8	1	1
NFKB1	-0.024	0.17	-10000	0	-0.46	67	67
EPO/EPOR (dimer)/JAK2/SOCS3	-0.035	0.094	0.27	1	-0.29	58	59
PTPN6	-0.014	0.15	-10000	0	-0.46	8	8
TEC/VAV2/GRB2	-0.018	0.18	-10000	0	-0.71	13	13
EPOR	-0.005	0.12	-10000	0	-0.8	11	11
INPP5D	0.011	0.037	-10000	0	-0.58	2	2
mol:GDP	-0.043	0.11	-10000	0	-0.68	1	1
SOS1	0.014	0	-10000	0	-10000	0	0
PLCG2	0.012	0.026	-10000	0	-0.58	1	1
CRKL/CBL/C3G	0.01	0.14	-10000	0	-0.72	1	1
VAV2	-0.021	0.17	-10000	0	-0.75	6	6
CBL	-0.005	0.15	-10000	0	-0.63	2	2
SHC/Grb2/SOS1	-0.046	0.12	-10000	0	-0.72	1	1
STAT5A	0.01	0.14	-10000	0	-0.64	3	3
GRB2	0.014	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.027	0.14	-10000	0	-0.67	3	3
LYN/PLCgamma2	-0.002	0.033	-10000	0	-0.52	2	2
PTPN11	0.014	0	-10000	0	-10000	0	0
BTK	-0.007	0.15	-10000	0	-0.63	2	2
BCL2	0.016	0.16	-10000	0	-0.74	9	9

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.02	0.077	-9999	-0.46	12	12
CRKL	0.012	0.036	-9999	-0.81	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.011	0.037	-9999	-0.58	2	2
ITGA4	-0.004	0.12	-9999	-0.81	11	11
alpha4/beta7 Integrin/MAdCAM1	-0.026	0.11	-9999	-0.48	27	27
EPO	-0.078	0.26	-9999	-0.81	57	57
alpha4/beta7 Integrin	-0.015	0.092	-9999	-0.59	13	13
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.014	0.093	-9999	-0.62	12	12
EPO/EPOR (dimer)	-0.081	0.21	-9999	-0.63	67	67
lamellipodium assembly	0	0.022	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.026	-9999	-0.42	2	2
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.017	0.13	-9999	-0.52	4	4
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
MADCAM1	-0.016	0.14	-9999	-0.81	16	16
cell adhesion	-0.026	0.11	-9999	-0.48	27	27
CRKL/CBL	-0.001	0.027	-9999	-0.62	1	1
ITGB1	0.012	0.036	-9999	-0.81	1	1
SRC	-0.024	0.17	-9999	-0.5	52	52
ITGB7	0.011	0.037	-9999	-0.58	2	2
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.061	0.17	-9999	-0.52	61	61
p130Cas/Crk/Dock1	0.002	0.15	-9999	-0.8	2	2
VCAM1	-0.063	0.23	-9999	-0.77	51	51
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.011	0.073	-9999	-0.48	12	12
BCAR1	-0.013	0.16	-9999	-0.46	52	52
EPOR	-0.004	0.12	-9999	-0.81	11	11
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0	0.023	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.014	0	-10000	0	-10000	0	0
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	0.011	0.037	-10000	0	-0.58	2	2
Cbp/p300/PCAF	-0.018	0.079	-10000	0	-0.67	1	1
EP300	0.012	0.026	-10000	0	-0.58	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.007	0.1	-10000	0	-0.48	10	10
KAT2B	-0.016	0.13	-10000	0	-0.58	26	26
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.028	0.11	0.22	2	-0.37	4	6
RAR alpha/9cRA/Cyclin H	-0.023	0.06	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.001	0.11	-10000	0	-0.43	15	15
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.022	0.081	-10000	0	-0.47	7	7
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-10000	0	-0.42	2	2
RXRs/RARs/NRIP1/9cRA	-0.002	0.14	-10000	0	-0.6	6	6
NCOA2	-0.034	0.16	-10000	0	-0.58	42	42
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.036	-10000	0	-0.58	2	2
RARG	0.013	0.026	-10000	0	-0.58	1	1
RAR gamma1/9cRA	-0.001	0.016	-10000	0	-0.35	1	1
MAPK3	0.014	0.001	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.007	0.068	-10000	0	-0.58	7	7
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.048	0.11	-10000	0	-0.45	11	11
RARA	-0.003	0.087	-10000	0	-0.27	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.021	0.16	-10000	0	-0.57	26	26
PRKCA	0.014	0.045	-10000	0	-0.7	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.019	0.15	-10000	0	-0.64	7	7
RXRG	-0.061	0.18	-10000	0	-0.38	116	116
RXRA	0.007	0.082	-10000	0	-0.33	1	1
RXRB	-0.015	0.12	-10000	0	-0.35	61	61
VDR/Vit D3/DNA	-0.002	0.026	-10000	0	-0.42	2	2
RBP1	-0.17	0.34	-10000	0	-0.8	117	117
CRBP1/9-cic-RA	-0.14	0.26	-10000	0	-0.62	117	117
RARB	-0.036	0.17	-10000	0	-0.58	45	45
PRKCG	-0.08	0.26	-10000	0	-0.8	59	59
MNAT1	0.014	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.015	0.15	-10000	0	-0.54	5	5
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.004	0.13	-10000	0	-0.55	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.11	-10000	0	-0.44	14	14
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.019	0.15	-10000	0	-0.64	7	7
positive regulation of DNA binding	-0.022	0.058	-10000	0	-10000	0	0
NRIP1	-0.019	0.16	-10000	0	-1.3	3	3
RXRs/RARs	-0.026	0.15	-10000	0	-0.46	20	20
RXRs/RXRs/DNA/9cRA	-0.049	0.11	-10000	0	-0.45	10	10
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.016	0.041	-10000	0	-10000	0	0
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0.011	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	0.002	0.095	-10000	0	-0.81	7	7
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	-0.1	0.28	-10000	0	-0.81	73	73
CDKN1A	0.029	0.033	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.008	0.071	-10000	0	-0.62	7	7
mol:Ca2+	-0.079	0.18	0.37	5	-0.44	99	104
AGT	-0.1	0.24	-10000	0	-0.59	99	99
CCNA2	0.029	0.074	-10000	0	-0.74	1	1
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	0.005	0.093	-10000	0	-0.41	25	25
CDK2/Cyclin E1	0.033	0.062	-10000	0	-10000	0	0
MAPK3	0.016	0.074	-10000	0	-0.62	7	7
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.074	-10000	0	-0.62	7	7
PTP4A1	0.023	0.072	-10000	0	-10000	0	0
PTP4A3	0.002	0.095	-10000	0	-0.81	7	7
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.014	0.079	-10000	0	-0.62	8	8
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.025	0.044	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.018	0.099	-10000	0	-0.74	1	1
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.005	0.043	0.37	7	-10000	0	7
RHOC	0.025	0.044	-10000	0	-10000	0	0
RHOA	0.025	0.044	-10000	0	-10000	0	0
cell motility	0.029	0.046	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.028	0.067	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.095	0.22	-10000	0	-0.62	80	80
ROCK1	0.029	0.046	-10000	0	-10000	0	0
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0.014	0	-10000	0	-10000	0	0
mitosis	0.023	0.072	-10000	0	-10000	0	0
ATF5	-0.004	0.12	-10000	0	-0.81	11	11

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.009	0.062	-10000	0	-0.81	3	3
ANTXR2	-0.004	0.12	-10000	0	-0.81	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.016	-10000	0	-0.097	14	14
monocyte activation	-0.025	0.11	-10000	0	-0.29	72	72
MAP2K2	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.002	0.013	-10000	0	-10000	0	0
MAP2K7	-0.002	0.013	-10000	0	-10000	0	0
MAP2K6	-0.018	0.069	-10000	0	-0.31	26	26
CYAA	0.003	0.079	-10000	0	-0.47	14	14
MAP2K4	-0.002	0.013	-10000	0	-10000	0	0
IL1B	-0.031	0.14	-10000	0	-0.46	52	52
Channel	-0.013	0.081	-10000	0	-0.5	14	14
NLRP1	-0.003	0.025	-10000	0	-0.48	1	1
CALM1	0.014	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.016	0.097	14	-10000	0	14
MAPK3	-0.002	0.013	-10000	0	-10000	0	0
MAPK1	-0.002	0.013	-10000	0	-10000	0	0
PGR	-0.046	0.11	-10000	0	-0.33	69	69
PA/Cellular Receptors	-0.015	0.088	-10000	0	-0.54	14	14
apoptosis	-0.003	0.016	-10000	0	-0.097	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.076	-10000	0	-0.45	14	14
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.024	0.17	-10000	0	-0.77	25	25
VCAM1	-0.026	0.11	-10000	0	-0.29	72	72
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.024	0.16	1	-10000	0	1
IL18	0.005	0.061	-10000	0	-0.3	19	19
negative regulation of macrophage activation	-0.003	0.016	-10000	0	-0.097	14	14
LEF	-0.003	0.016	-10000	0	-0.097	14	14
CASP1	-0.003	0.016	-10000	0	-0.22	1	1
mol:cAMP	-0.003	0.019	-10000	0	-10000	0	0
necrosis	-0.003	0.016	-10000	0	-0.097	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.004	0.08	-10000	0	-0.48	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.12	0.3	-9999	-0.81	86	86
alphaV beta3 Integrin	-0.028	0.12	-9999	-0.57	25	25
PTK2	-0.028	0.091	-9999	-0.65	3	3
positive regulation of JNK cascade	-0.013	0.053	-9999	-0.3	13	13
CDC42/GDP	0.037	0.086	-9999	-0.4	13	13
Rac1/GDP	0.039	0.085	-9999	-0.4	13	13
RAP1B	0.012	0.036	-9999	-0.81	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.012	0.026	-9999	-0.58	1	1
CDC42/GTP	-0.016	0.064	-9999	-0.37	13	13
nectin-3/I-afadin	-0.027	0.12	-9999	-0.52	27	27
RAPGEF1	0.034	0.093	-9999	-0.44	13	13
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.027	0.1	-9999	-0.51	13	13
PDGFB-D/PDGFRB	-0.12	0.3	-9999	-0.81	86	86
TLN1	0.021	0.061	-9999	-0.46	2	2
Rap1/GTP	-0.014	0.056	-9999	-0.38	3	3
IQGAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.022	-9999	-0.49	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.027	0.12	-9999	-0.52	27	27
PVR	0.01	0.051	-9999	-0.81	2	2
Necl-5(dimer)	0.01	0.051	-9999	-0.81	2	2
mol:GDP	0.034	0.1	-9999	-0.49	13	13
MLLT4	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.095	0.18	-9999	-0.46	99	99
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.42	3	3
positive regulation of lamellipodium assembly	-0.019	0.06	-9999	-0.31	13	13
PVRL1	0.01	0.045	-9999	-0.58	3	3
PVRL3	-0.023	0.16	-9999	-0.7	27	27
PVRL2	0.012	0.036	-9999	-0.81	1	1
PIK3R1	0.011	0.037	-9999	-0.58	2	2
CDH1	0.007	0.063	-9999	-0.58	6	6
CLDN1	-0.018	0.14	-9999	-0.65	25	25
JAM-A/CLDN1	-0.039	0.12	-9999	-0.49	23	23
SRC	-0.026	0.1	-9999	-0.57	13	13
ITGB3	-0.017	0.15	-9999	-0.73	21	21
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.42	3	3
FARP2	0.031	0.098	-9999	-0.48	13	13
RAC1	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.025	0.1	-9999	-0.53	16	16
nectin-1/I-afadin	-0.002	0.031	-9999	-0.42	3	3
nectin-2/I-afadin	-0.001	0.027	-9999	-0.62	1	1
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.025	0.1	-9999	-0.53	14	14
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.012	0.026	-9999	-0.58	1	1
positive regulation of filopodium formation	-0.013	0.053	-9999	-0.3	13	13
alphaV/beta3 Integrin/Talin	0.014	0.11	-9999	-0.42	24	24
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.027	-9999	-0.62	1	1
nectin-2(dimer)/I-afadin/I-afadin	-0.001	0.027	-9999	-0.62	1	1
PIP5K1C	0.015	0.056	-9999	-0.36	2	2
VAV2	0.021	0.11	-9999	-0.49	13	13
RAP1/GDP	-0.016	0.065	-9999	-0.45	3	3
ITGAV	0.006	0.076	-9999	-0.76	5	5
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.024	0.1	-9999	-0.53	15	15
nectin-3(dimer)/I-afadin/I-afadin	-0.027	0.12	-9999	-0.52	27	27
Rac1/GTP	-0.022	0.072	-9999	-0.38	13	13
PTPRM	0.006	0.062	-9999	-0.27	16	16
E-cadherin/beta catenin/alpha catenin	-0.006	0.048	-9999	-0.51	3	3
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.016	0.21	-9999	-0.63	7	7
CRP	-0.036	0.24	-9999	-0.74	21	21
cell cycle arrest	-0.027	0.23	-9999	-0.67	14	14
TIMP1	-0.01	0.2	-9999	-0.68	11	11
IL6ST	-0.058	0.2	-9999	-0.57	65	65
Rac1/GDP	-0.012	0.16	-9999	-0.56	15	15
AP1	0.005	0.13	-9999	-0.55	4	4
GAB2	0.011	0.045	-9999	-0.58	3	3
TNFSF11	-0.082	0.3	-9999	-0.7	47	47
HSP90B1	0.028	0.05	-9999	-10000	0	0
GAB1	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.016	0.15	-9999	-0.55	17	17
AKT1	0.056	0.029	-9999	-10000	0	0
FOXO1	0.063	0.027	-9999	-10000	0	0
MAP2K6	-0.028	0.16	-9999	-0.55	21	21
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	-0.003	0.17	-9999	-0.58	9	9
MITF	-0.028	0.17	-9999	-0.54	25	25
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0.036	-9999	-0.81	1	1
A2M	0.021	0.03	-9999	-0.65	1	1
CEBPB	0.02	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.013	0.075	-9999	-0.43	3	3
STAT3	-0.028	0.24	-9999	-0.7	14	14
STAT1	-0.022	0.09	-9999	-0.48	8	8
CEBPD	-0.016	0.21	-9999	-0.63	7	7
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	0.022	0.027	-9999	-0.41	2	2
JUN	0.013	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.019	0.16	-9999	-0.51	24	24
MAPK11	-0.016	0.15	-9999	-0.55	17	17
STAT3 (dimer)/FOXO1	0.028	0.2	-9999	-0.55	2	2
GRB2/SOS1/GAB family	-0.048	0.11	-9999	-0.53	9	9
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.023	0.15	-9999	-0.56	18	18
GRB2	0.014	0.001	-9999	-10000	0	0
JAK2	0.012	0.026	-9999	-0.58	1	1
LBP	-0.11	0.36	-9999	-0.9	73	73
PIK3R1	0.013	0.037	-9999	-0.58	2	2
JAK1	0.015	0.004	-9999	-10000	0	0
MYC	-0.016	0.21	-9999	-0.63	7	7
FGG	-0.052	0.27	-9999	-0.75	33	33
macrophage differentiation	-0.027	0.23	-9999	-0.67	14	14
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.064	0.15	-9999	-0.53	25	25
JUNB	-0.016	0.21	-9999	-0.63	4	4
FOS	-0.063	0.2	-9999	-0.58	67	67
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.028	0.16	-9999	-0.53	21	21
STAT1/PIAS1	-0.025	0.15	-9999	-0.53	13	13
GRB2/SOS1/GAB family/SHP2/PI3K	0.039	0.034	-9999	-10000	0	0
STAT3 (dimer)	-0.027	0.24	-9999	-0.69	14	14
PRKCD	0.005	0.18	-9999	-0.64	5	5
IL6R	0.006	0.073	-9999	-0.58	8	8
SOCS3	-0.011	0.15	-9999	-0.69	6	6
gp130 (dimer)/JAK1/JAK1/LMO4	-0.016	0.12	-9999	-0.37	2	2
Rac1/GTP	-0.017	0.16	-9999	-0.56	15	15
HCK	0.006	0.076	-9999	-0.76	5	5
MAPKKK cascade	0.029	0.071	-9999	-0.57	3	3
bone resorption	-0.076	0.29	-9999	-0.66	48	48
IRF1	-0.016	0.21	-9999	-0.63	7	7
mol:GDP	-0.022	0.16	-9999	-0.56	19	19
SOS1	0.013	0.004	-9999	-10000	0	0
VAV1	-0.022	0.16	-9999	-0.57	19	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.02	0.15	-9999	-0.63	16	16
PTPN11	-0.002	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.032	0.15	-9999	-0.45	58	58
gp130 (dimer)/TYK2/TYK2/LMO4	-0.022	0.13	-9999	-0.43	7	7
gp130 (dimer)/JAK2/JAK2/LMO4	-0.021	0.12	-9999	-0.46	3	3
IL6	-0.046	0.19	-9999	-0.62	51	51
PIAS3	0.014	0	-9999	-10000	0	0
PTPRE	0.01	0.012	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
RAC1	0.014	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.038	0.15	-9999	-0.51	23	23
LMO4	0.015	0.011	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.11	0.17	-9999	-0.67	13	13
MCL1	0.062	0.027	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.014	0	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
CRKL	-0.026	0.12	-9999	-0.41	7	7
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.012	0.036	-9999	-0.81	1	1
IRS1/Crk	-0.025	0.12	-9999	-0.4	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.056	0.12	-9999	-0.47	6	6
AKT1	0	0.11	-9999	-0.47	2	2
BAD	0.009	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.025	0.12	-9999	-0.4	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.026	0.12	-9999	-0.4	6	6
RAF1	0.014	0.099	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.045	0.1	-9999	-0.52	1	1
YWHAZ	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.037	0.13	-9999	-0.32	87	87
PIK3CA	0.014	0	-9999	-10000	0	0
RPS6KB1	0	0.11	-9999	-0.47	2	2
GNB2L1	0.014	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.011	0.088	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.04	0.09	-9999	-0.55	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.042	0.094	-9999	-0.38	5	5
IGF-1R heterotetramer	0	0.045	-9999	-0.79	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.025	0.12	-9999	-0.4	6	6
Crk/p130 Cas/Paxillin	-0.042	0.094	-9999	-0.49	1	1
IGF1R	0	0.045	-9999	-0.8	1	1
IGF1	-0.087	0.23	-9999	-0.6	86	86
IRS2/Crk	-0.016	0.12	-9999	-0.54	2	2
PI3K	-0.046	0.1	-9999	-0.54	2	2
apoptosis	-0.016	0.091	-9999	-10000	0	0
HRAS/GDP	-0.001	0.027	-9999	-0.63	1	1
PRKCD	-0.023	0.15	-9999	-0.36	82	82
RAF1/14-3-3 E	0.021	0.089	-9999	-10000	0	0
BAD/14-3-3	0.016	0.096	-9999	-10000	0	0
PRKCZ	0	0.11	-9999	-0.47	2	2
Crk/p130 Cas/Paxillin/FAK1	-0.031	0.07	-9999	-10000	0	0
PTPN1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.033	0.16	-9999	-0.38	86	86
BCAR1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.048	0.11	-9999	-0.43	6	6
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
IRS1/NCK2	-0.025	0.12	-9999	-0.4	6	6
GRB10	0.012	0.036	-9999	-0.81	1	1
PTPN11	-0.025	0.12	-9999	-0.4	6	6
IRS1	-0.037	0.13	-9999	-0.32	87	87
IRS2	-0.026	0.12	-9999	-0.43	7	7
IGF-1R heterotetramer/IGF1	-0.074	0.17	-9999	-0.44	87	87
GRB2	0.014	0	-9999	-10000	0	0
PDPK1	-0.008	0.11	-9999	-0.5	2	2
YWHAE	0.014	0	-9999	-10000	0	0
PRKD1	-0.027	0.16	-9999	-0.38	85	85
SHC1	0.014	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.007	0.038	0.25	9	-10000	0	9
RFC1	0.007	0.038	0.25	9	-10000	0	9
PRKDC	0.007	0.038	0.25	9	-10000	0	9
RIPK1	0.014	0.003	-10000	0	-10000	0	0
CASP7	-0.012	0.04	0.23	4	-10000	0	4
FASLG/FAS/FADD/FAF1	-0.05	0.12	-10000	0	-0.43	9	9
MAP2K4	-0.005	0.13	-10000	0	-0.43	12	12
mol:ceramide	-0.023	0.14	-10000	0	-0.47	14	14
GSN	0.007	0.038	0.25	9	-10000	0	9
FASLG/FAS/FADD/FAF1/Caspase 8	-0.021	0.12	-10000	0	-0.44	10	10
FAS	0.011	0.037	-10000	0	-0.58	2	2
BID	0.002	0.046	0.3	1	-0.55	2	3
MAP3K1	0.009	0.078	-10000	0	-10000	0	0
MAP3K7	0.013	0.004	-10000	0	-10000	0	0
RB1	0.006	0.044	0.26	4	-0.34	2	6
CFLAR	0.014	0.003	-10000	0	-10000	0	0
HGF/MET	-0.03	0.11	-10000	0	-0.56	11	11
ARHGDIB	0.007	0.038	0.25	6	-10000	0	6
FADD	-0.081	0.26	-10000	0	-0.81	60	60
actin filament polymerization	-0.007	0.038	-10000	0	-0.25	9	9
NFKB1	-0.031	0.063	-10000	0	-0.27	7	7
MAPK8	-0.013	0.16	-10000	0	-0.53	14	14
DFFA	0.007	0.038	0.25	9	-10000	0	9
DNA fragmentation during apoptosis	0.005	0.047	0.25	8	-0.43	2	10
FAS/FADD/MET	-0.068	0.18	-10000	0	-0.55	63	63
CFLAR/RIP1	0.001	0.004	-10000	0	-10000	0	0
FAIM3	0	0.1	-10000	0	-0.78	9	9
FAF1	0.014	0.005	-10000	0	-10000	0	0
PARP1	0.007	0.038	0.25	9	-10000	0	9
DFFB	0.005	0.047	0.25	8	-0.43	2	10
CHUK	-0.025	0.054	-10000	0	-10000	0	0
FASLG	-0.042	0.2	-10000	0	-0.72	39	39
FAS/FADD	-0.073	0.2	-10000	0	-0.62	61	61
HGF	-0.015	0.14	-10000	0	-0.65	22	22
LMNA	0.006	0.035	-10000	0	-10000	0	0
CASP6	0.007	0.038	0.25	6	-10000	0	6
CASP10	0.013	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.045	0.3	9	-10000	0	9
PTPN13	0.001	0.085	-10000	0	-0.58	11	11
CASP8	0.006	0.049	0.37	9	-10000	0	9
IL6	-0.089	0.36	-10000	0	-1.2	51	51
MET	0.005	0.08	-10000	0	-0.73	6	6
ICAD/CAD	0.005	0.044	-10000	0	-0.48	1	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.024	0.14	-10000	0	-0.48	14	14
activation of caspase activity by cytochrome c	0.002	0.046	0.3	1	-0.55	2	3
PAK2	0.007	0.038	0.25	6	-10000	0	6
BCL2	0.002	0.092	-10000	0	-0.68	9	9

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.029	0.032	-9999	-10000	0	0
epithelial cell differentiation	-0.004	0.033	-9999	-10000	0	0
CYFIP2	0.011	0.044	-9999	-0.69	2	2
ENAH	0.064	0.046	-9999	-0.54	1	1
EGFR	-0.015	0.15	-9999	-0.76	19	19
EPHA2	0.006	0.068	-9999	-0.58	7	7
MYO6	0.036	0.035	-9999	-10000	0	0
CTNNB1	0.012	0.026	-9999	-0.58	1	1
ABI1/Sra1/Nap1	-0.003	0.036	-9999	-0.53	2	2
AQP5	-0.3	0.22	-9999	-0.45	338	338
CTNND1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.036	0.035	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.002	0.12	-9999	-0.43	32	32
EGF	-0.1	0.24	-9999	-0.58	101	101
NCKAP1	0.012	0.036	-9999	-0.81	1	1
AQP3	-0.13	0.21	-9999	-0.46	148	148
cortical microtubule organization	-0.004	0.033	-9999	-10000	0	0
GO:0000145	0.035	0.033	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.033	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GDP	-0.006	0.043	-9999	-0.46	2	2
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.005	0.041	-9999	-0.48	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.048	0.036	-9999	-10000	0	0
PVRL2	0.012	0.036	-9999	-0.81	1	1
ZYX	0.036	0.035	-9999	-10000	0	0
ARF6/GTP	-0.005	0.037	-9999	-0.44	1	1
CDH1	0.007	0.063	-9999	-0.58	6	6
EGFR/EGFR/EGF/EGF	-0.067	0.13	-9999	-0.45	20	20
RhoA/GDP	-0.004	0.03	-9999	-10000	0	0
actin cytoskeleton organization	0.043	0.034	-9999	-10000	0	0
IGF-1R heterotetramer	0.012	0.036	-9999	-0.81	1	1
GIT1	0.014	0	-9999	-10000	0	0
IGF1R	0.012	0.036	-9999	-0.81	1	1
IGF1	-0.086	0.22	-9999	-0.59	86	86
DIAPH1	-0.002	0.031	-9999	-0.57	1	1
Wnt receptor signaling pathway	0.004	0.033	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.006	0.043	-9999	-0.47	2	2
CTNNA1	0.014	0	-9999	-10000	0	0
VCL	0.043	0.035	-9999	-10000	0	0
EFNA1	0.012	0.036	-9999	-0.81	1	1
LPP	0.042	0.041	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.008	0.051	-9999	-0.5	3	3
SEC6/SEC8	-0.004	0.03	-9999	-10000	0	0
MGAT3	0.002	0.12	-9999	-0.44	32	32
HGF/MET	-0.021	0.09	-9999	-0.52	11	11
HGF	-0.015	0.14	-9999	-0.65	22	22
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.029	0.032	-9999	-10000	0	0
actin cable formation	0.081	0.041	-9999	-0.37	1	1
KIAA1543	0.017	0.11	-9999	-0.65	7	7
KIFC3	0.036	0.035	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
EXOC3	0.014	0	-9999	-10000	0	0
ACTN1	0.035	0.041	-9999	-0.44	1	1
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.004	0.033	-9999	-10000	0	0
EXOC4	0.014	0	-9999	-10000	0	0
STX4	0.036	0.035	-9999	-10000	0	0
PIP5K1C	0.036	0.035	-9999	-10000	0	0
LIMA1	0.014	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
ROCK1	-0.006	0.037	-9999	-10000	0	0
adherens junction assembly	0.033	0.11	-9999	-0.64	7	7
IGF-1R heterotetramer/IGF1	-0.047	0.1	-9999	-0.42	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.027	-9999	-0.62	1	1
MET	0.005	0.08	-9999	-0.73	6	6
PLEKHA7	0.017	0.089	-9999	-0.56	4	4
mol:GTP	-0.005	0.041	-9999	-0.48	1	1
establishment of epithelial cell apical/basal polarity	0.062	0.037	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.029	0.032	-9999	-10000	0	0
regulation of cell-cell adhesion	0.043	0.034	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.029	0.032	-9999	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.16	0.32	-9999	-1.2	3	3
PLK1	0.083	0.083	-9999	-0.69	2	2
BIRC5	0.06	0.16	-9999	-0.61	22	22
HSPA1B	0.15	0.32	-9999	-1.2	3	3
MAP2K1	0.046	0.037	-9999	-10000	0	0
BRCA2	0.15	0.33	-9999	-1.3	5	5
FOXM1	0.15	0.36	-9999	-1.4	6	6
XRCC1	0.16	0.32	-9999	-1.2	3	3
FOXM1B/p19	-0.18	0.26	-9999	-1	21	21
Cyclin D1/CDK4	0.1	0.36	-9999	-1.1	8	8
CDC2	0.15	0.33	-9999	-1.1	6	6
TGFA	0.11	0.36	-9999	-1.1	8	8
SKP2	0.16	0.32	-9999	-1.2	4	4
CCNE1	0.009	0.095	-9999	-0.8	7	7
CKS1B	0.15	0.33	-9999	-1.2	6	6
RB1	-0.048	0.11	-9999	-0.72	5	5
FOXM1C/SP1	0.15	0.32	-9999	-1.3	5	5
AURKB	0.074	0.12	-9999	-0.66	10	10
CENPF	0.16	0.32	-9999	-1.2	3	3
CDK4	0.024	0.017	-9999	-10000	0	0
MYC	0.16	0.29	-9999	-1	3	3
CHEK2	0.046	0.037	-9999	-10000	0	0
ONECUT1	0.1	0.38	-9999	-1.1	13	13
CDKN2A	-0.35	0.39	-9999	-0.76	238	238
LAMA4	0.14	0.35	-9999	-1.1	7	7
FOXM1B/HNF6	0.094	0.42	-9999	-1.3	14	14
FOS	0.051	0.5	-9999	-1.1	68	68
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.14	0.33	-9999	-1.1	5	5
response to radiation	0.027	0.035	-9999	-10000	0	0
CENPB	0.16	0.32	-9999	-1.2	3	3
CENPA	0.15	0.33	-9999	-1.2	6	6
NEK2	0.16	0.32	-9999	-1.2	4	4
HIST1H2BA	0.15	0.31	-9999	-1.2	3	3
CCNA2	0.018	0.038	-9999	-0.82	1	1
EP300	0.012	0.026	-9999	-0.58	1	1
CCNB1/CDK1	0.15	0.34	-9999	-1.4	4	4
CCNB2	0.16	0.32	-9999	-1.3	4	4
CCNB1	0.16	0.33	-9999	-1.2	4	4
ETV5	0.15	0.32	-9999	-1.2	3	3
ESR1	0.12	0.38	-9999	-1.1	20	20
CCND1	0.11	0.38	-9999	-1	14	14
GSK3A	0.041	0.032	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.044	0.083	-9999	-0.53	8	8
CDK2	0.02	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.032	0.039	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.07	0.19	-9999	-1.1	7	7
GAS1	0.15	0.34	-9999	-1.2	7	7
MMP2	0.11	0.37	-9999	-1.1	10	10
RB1/FOXM1C	0.12	0.36	-9999	-1.2	6	6
CREBBP	0.014	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.041	0.099	-10000	0	-0.63	5	5
UGCG	-0.009	0.12	-10000	0	-0.62	19	19
AKT1/mTOR/p70S6K/Hsp90/TERT	0.015	0.13	-10000	0	-0.42	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0	0.12	-10000	0	-0.61	19	19
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.022	0.077	-10000	0	-0.46	9	9
FRAP1	0.053	0.12	-10000	0	-0.5	13	13
FOXO3	0.061	0.1	-10000	0	-0.55	3	3
AKT1	0.055	0.11	-10000	0	-0.47	10	10
GAB2	0.011	0.045	-10000	0	-0.58	3	3
SMPD1	0.014	0.025	-10000	0	-10000	0	0
SGMS1	0.014	0.025	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0.024	-10000	0	-0.36	2	2
CALM1	0.014	0	-10000	0	-10000	0	0
cell proliferation	0.029	0.082	-10000	0	-0.42	5	5
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.023	0.029	-10000	0	-0.42	2	2
RPS6KB1	0.008	0.066	-10000	0	-10000	0	0
mol:sphingomyelin	-0.001	0.003	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.018	0.16	-10000	0	-0.8	22	22
PIK3R1	0.014	0.037	-10000	0	-0.58	2	2
JAK1	0.017	0.002	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	0.061	0.096	-10000	0	-0.49	3	3
MYB	-0.097	0.36	-10000	0	-1.2	51	51
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.042	0.12	-10000	0	-0.54	10	10
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.023	0.061	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.042	0.11	-10000	0	-0.52	10	10
Rac1/GDP	0.027	0.023	-10000	0	-10000	0	0
T cell proliferation	0.051	0.11	-10000	0	-0.51	8	8
SHC1	0.014	0.002	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.001	0.021	-10000	0	-0.064	51	51
PRKCZ	0.051	0.11	-10000	0	-0.53	8	8
NF kappa B1 p50/RelA	-0.021	0.076	-10000	0	-0.45	9	9
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.034	0.11	-10000	0	-0.52	13	13
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.06	0.24	-10000	0	-0.81	47	47
IL2RB	0.004	0.098	-10000	0	-0.78	8	8
TERT	-0.17	0.34	-10000	0	-0.81	115	115
E2F1	-0.031	0.15	-10000	0	-0.43	51	51
SOS1	0.014	0.002	-10000	0	-10000	0	0
RPS6	0.014	0	-10000	0	-10000	0	0
mol:cAMP	0	0.01	0.031	51	-10000	0	51
PTPN11	0.014	0.002	-10000	0	-10000	0	0
IL2RG	-0.009	0.14	-10000	0	-0.78	17	17
actin cytoskeleton organization	0.051	0.11	-10000	0	-0.51	8	8
GRB2	0.014	0.002	-10000	0	-10000	0	0
IL2	0.007	0.036	-10000	0	-0.8	1	1
PIK3CA	0.017	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.024	-10000	0	-10000	0	0
LCK	-0.002	0.12	-10000	0	-0.8	12	12
BCL2	0.053	0.14	-10000	0	-0.75	10	10

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.038	0.098	-10000	0	-10000	0	0
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.042	0.11	-10000	0	-0.33	66	66
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	0.011	0.028	0.085	66	-10000	0	66
GNAL	-0.061	0.2	-10000	0	-0.58	66	66
GNG2	0.014	0	-10000	0	-10000	0	0
CRH	0.001	0.004	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.042	-10000	0	-0.36	7	7
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.002	0.16	-9999	-0.57	15	15
MAP3K8	0.009	0.045	-9999	-0.58	3	3
FOS	0.009	0.12	-9999	-0.48	14	14
PRKCA	0.01	0.044	-9999	-0.69	2	2
PTPN7	-0.025	0.18	-9999	-0.8	25	25
HRAS	0.012	0.036	-9999	-0.81	1	1
PRKCB	0.001	0.096	-9999	-0.76	8	8
NRAS	0.013	0.001	-9999	-10000	0	0
RAS family/GTP	-0.003	0.037	-9999	-0.49	3	3
MAPK3	0.012	0.082	-9999	-0.38	11	11
MAP2K1	0.028	0.07	-9999	-0.45	6	6
ELK1	0.01	0.038	-9999	-0.84	1	1
BRAF	-0.01	0.052	-9999	-0.41	6	6
mol:GTP	-0.001	0.002	-9999	-0.006	67	67
MAPK1	0.012	0.082	-9999	-0.36	13	13
RAF1	-0.01	0.052	-9999	-0.41	6	6
KRAS	0.01	0.051	-9999	-0.81	2	2

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.031	0.047	-9999	-10000	0	0
STMN1	0.011	0.11	-9999	-0.69	12	12
Aurora B/RasGAP/Survivin	-0.007	0.15	-9999	-0.61	27	27
Chromosomal passenger complex/Cul3 protein complex	0.023	0.079	-9999	-0.44	10	10
BIRC5	-0.019	0.16	-9999	-0.8	22	22
DES	-0.32	0.27	-9999	-0.55	293	293
Aurora C/Aurora B/INCENP	0.009	0.093	-9999	-0.51	15	15
Aurora B/TACC1	0.005	0.079	-9999	-0.5	12	12
Aurora B/PP2A	0.007	0.087	-9999	-0.61	10	10
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.015	0.024	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.004	0.12	-9999	-0.62	19	19
Cul3 protein complex	-0.006	0.045	-9999	-10000	0	0
KIF2C	0.019	0.048	-9999	-0.35	5	5
PEBP1	0.014	0.002	-9999	-10000	0	0
KIF20A	0.013	0.001	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.005	0.095	-9999	-0.62	11	11
SEPT1	-0.001	0.11	-9999	-0.81	9	9
SMC2	0.014	0	-9999	-10000	0	0
SMC4	0.012	0.036	-9999	-0.81	1	1
NSUN2/NPM1/Nucleolin	0.025	0.054	-9999	-0.38	5	5
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.003	-9999	-10000	0	0
H3F3B	0.014	0.052	-9999	-0.36	10	10
AURKB	0.006	0.11	-9999	-0.81	10	10
AURKC	0.003	0.088	-9999	-0.74	7	7
CDCA8	0.014	0.037	-9999	-0.82	1	1
cytokinesis	-0.021	0.085	-9999	-0.6	6	6
Aurora B/Septin1	0.006	0.11	-9999	-0.49	15	15
AURKA	-0.006	0.12	-9999	-0.81	12	12
INCENP	0.015	0.003	-9999	-10000	0	0
KLHL13	0.01	0.045	-9999	-0.58	3	3
BUB1	0.013	0.001	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.004	0.14	-9999	-0.56	27	27
EVI5	0.015	0.001	-9999	-10000	0	0
RhoA/GTP	-0.011	0.054	-9999	-0.44	4	4
SGOL1	0.014	0	-9999	-10000	0	0
CENPA	0.016	0.087	-9999	-0.47	12	12
NCAPG	0.014	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.007	0.087	-9999	-0.61	10	10
NCAPD2	0.009	0.062	-9999	-0.81	3	3
Aurora B/PP1-gamma	0.007	0.087	-9999	-0.61	10	10
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	0.009	0.062	-9999	-0.81	3	3
NPM1	0.005	0.058	-9999	-0.4	10	10
RASA1	0.011	0.037	-9999	-0.58	2	2
KLHL9	0.007	0.063	-9999	-0.58	6	6
mitotic prometaphase	0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.087	-9999	-0.6	10	10
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.012	0.06	-9999	-0.43	8	8
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	0.005	0.058	-9999	-0.4	10	10
MYLK	0.008	0.074	-9999	-0.38	17	17
KIF23	0.014	0.002	-9999	-10000	0	0
VIM	0.011	0.11	-9999	-0.65	13	13
RACGAP1	0.014	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.005	0.058	-9999	-0.4	10	10
Chromosomal passenger complex	0.026	0.074	-9999	-0.46	8	8
Chromosomal passenger complex/EVI5	0.029	0.14	-9999	-0.53	27	27
TACC1	0.011	0.037	-9999	-0.58	2	2
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.036	0.18	-9999	-0.84	20	20
MAP4K1	-0.007	0.13	-9999	-0.76	14	14
MAP3K8	0.01	0.045	-9999	-0.58	3	3
PRKCB	0.002	0.095	-9999	-0.75	8	8
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.012	0.036	-9999	-0.81	1	1
MAP3K1	0.029	0.099	-9999	-0.53	12	12
JUN	0.024	0.095	-9999	-0.58	10	10
MAP3K7	0.029	0.099	-9999	-0.53	12	12
GRAP2	-0.002	0.1	-9999	-0.67	12	12
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0.037	0.098	-9999	-0.5	12	12
LAT	-0.009	0.13	-9999	-0.81	14	14
LCP2	0.009	0.062	-9999	-0.81	3	3
MAPK8	0.017	0.1	-9999	-0.55	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.021	0.1	-9999	-0.57	12	12
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.034	0.17	-9999	-0.79	20	20

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.006	0.055	-9999	-0.65	3	3
VDR	0.011	0.037	-9999	-0.58	2	2
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.017	0.11	-9999	-0.45	5	5
RXRs/LXRs/DNA/Oxysterols	0.025	0.12	-9999	-0.51	5	5
MED1	0.012	0.036	-9999	-0.81	1	1
mol:9cRA	0.005	0.011	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.007	0.11	-9999	-0.5	3	3
RXRs/NUR77	-0.004	0.13	-9999	-0.49	8	8
RXRs/PPAR	-0.094	0.16	-9999	-0.5	17	17
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-9999	-0.42	2	2
RARs/VDR/DNA/Vit D3	-0.027	0.087	-9999	-0.52	2	2
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.036	-9999	-0.58	2	2
RARs/RARs/DNA/9cRA	-0.026	0.085	-9999	-0.46	1	1
RARG	0.012	0.026	-9999	-0.58	1	1
RPS6KB1	0.013	0.041	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.007	0.11	-9999	-0.5	3	3
THRA	0.014	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.026	-9999	-0.42	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.002	0.13	-9999	-0.45	11	11
NR1H4	0.003	0.036	-9999	-0.81	1	1
RXRs/LXRs/DNA	0.016	0.13	-9999	-0.72	1	1
NR1H2	0.019	0.008	-9999	-10000	0	0
NR1H3	0.01	0.088	-9999	-0.8	6	6
RXRs/VDR/DNA/Vit D3	0	0.12	-9999	-0.44	7	7
NR4A1	0.002	0.081	-9999	-0.58	10	10
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.004	0.086	-9999	-0.32	5	5
RXRG	-0.059	0.2	-9999	-0.6	64	64
RXR alpha/CCPG	0.024	0.006	-9999	-10000	0	0
RXRA	0.019	0.008	-9999	-10000	0	0
RXRB	0.019	0.009	-9999	-10000	0	0
THRB	-0.032	0.16	-9999	-0.58	40	40
PPARG	-0.21	0.29	-9999	-0.58	197	197
PPARD	0.014	0	-9999	-10000	0	0
TNF	0.013	0.18	-9999	-0.7	25	25
mol:Oxysterols	0.005	0.01	-9999	-10000	0	0
cholesterol transport	0.025	0.12	-9999	-0.5	5	5
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.038	0.17	-9999	-0.58	45	45
RXRs/NUR77/BCL2	-0.009	0.11	-9999	-0.59	2	2
SREBF1	0.033	0.11	-9999	-0.54	1	1
RXRs/RXRs/DNA/9cRA	-0.002	0.13	-9999	-0.45	11	11
ABCA1	0.03	0.13	-9999	-0.81	4	4
RARs/THRs	-0.047	0.11	-9999	-0.55	4	4
RXRs/FXR	-0.005	0.12	-9999	-0.47	8	8
BCL2	0.002	0.092	-9999	-0.68	9	9

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.12	0.3	-9999	-0.81	86	86
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.023	0.064	-9999	-0.42	2	2
GNAO1	0.009	0.069	-9999	-0.76	4	4
S1P/S1P3/G12/G13	0.021	0.061	-9999	-0.5	5	5
AKT1	-0.044	0.093	-9999	-0.37	8	8
AKT3	0.036	0.1	-9999	-0.67	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.12	0.3	-9999	-0.81	86	86
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.014	0.026	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.008	0.069	-9999	-0.62	6	6
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.03	0.077	-9999	-0.56	4	4
MAPK3	0.037	0.074	-9999	-0.53	4	4
MAPK1	0.037	0.074	-9999	-0.53	4	4
JAK2	0.033	0.093	-9999	-0.5	8	8
CXCR4	0.021	0.12	-9999	-0.53	20	20
FLT1	0.015	0.036	-9999	-0.8	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.037	0.074	-9999	-0.53	4	4
S1P/S1P3/Gi	0.03	0.078	-9999	-0.57	4	4
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.06	-9999	-0.52	4	4
VEGFA	0.005	0.095	-9999	-0.8	7	7
S1P/S1P2/Gi	0.031	0.059	-9999	-0.47	2	2
VEGFR1 homodimer/VEGFA homodimer	0.019	0.079	-9999	-0.61	8	8
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.014	0.12	-9999	-0.53	6	6
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.012	0.14	-9999	-0.73	19	19
G12/G13	-0.005	0.054	-9999	-0.62	4	4
GNA14	-0.072	0.21	-9999	-0.58	75	75
GNA15	0.011	0.037	-9999	-0.58	2	2
GNA12	0.007	0.072	-9999	-0.81	4	4
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.052	-9999	-0.58	4	4
Rac1/GTP	-0.014	0.06	-9999	-0.52	4	4

×

Sphingosine 1-phosphate (S1P) pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0	-9999	-10000	0	0
SPHK1	-0.01	0.14	-9999	-0.81	15	15
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.013	0.057	-9999	-0.28	19	19
GNAO1	0.008	0.067	-9999	-0.75	4	4
mol:Sphinganine-1-P	0.006	0.11	-9999	-0.62	15	15
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.01	0.052	-9999	-0.45	4	4
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.005	0.054	-9999	-0.62	4	4
S1PR3	0.006	0.068	-9999	-0.62	6	6
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.009	0.045	-9999	-10000	0	0
S1PR5	0.008	0.062	-9999	-0.69	4	4
S1PR4	-0.032	0.19	-9999	-0.8	29	29
GNAI1	0.012	0.026	-9999	-0.58	1	1
S1P/S1P5/G12	0.018	0.072	-9999	-0.48	6	6
S1P/S1P3/Gq	-0.01	0.12	-9999	-0.5	8	8
S1P/S1P4/Gi	0.015	0.09	-9999	-0.46	4	4
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.014	0.14	-9999	-0.74	19	19
GNA14	-0.072	0.21	-9999	-0.58	75	75
GNA15	0.011	0.037	-9999	-0.58	2	2
GNA12	0.007	0.072	-9999	-0.81	4	4
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.052	-9999	-0.58	4	4
ABCC1	0.007	0.072	-9999	-0.81	4	4

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.004	-9999	-10000	0	0
CLOCK	0.01	0.063	-9999	-0.57	6	6
TIMELESS/CRY2	0.045	0.013	-9999	-10000	0	0
DEC1/BMAL1	-0.1	0.23	-9999	-0.62	87	87
ATR	0.014	0	-9999	-10000	0	0
NR1D1	0.044	0.015	-9999	-10000	0	0
ARNTL	0.017	0	-9999	-10000	0	0
TIMELESS	0.044	0.015	-9999	-10000	0	0
NPAS2	0.009	0.068	-9999	-0.57	7	7
CRY2	0.014	0	-9999	-10000	0	0
mol:CO	-0.015	0	-9999	-10000	0	0
CHEK1	0.014	0	-9999	-10000	0	0
mol:HEME	0.015	0	-9999	-10000	0	0
PER1	0.012	0.026	-9999	-0.58	1	1
BMAL/CLOCK/NPAS2	0.037	0.063	-9999	-0.66	1	1
BMAL1/CLOCK	0.01	0.1	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.004	-9999	-10000	0	0
mol:NADPH	0.015	0	-9999	-10000	0	0
PER1/TIMELESS	0.045	0.019	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.13	0.3	-9999	-0.81	87	87

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.069	-10000	0	-0.62	6	6
MAP4K4	0.029	0.081	-10000	0	-0.41	9	9
BAG4	0.011	0.037	-10000	0	-0.58	2	2
PKC zeta/ceramide	-0.015	0.043	0.21	1	-0.36	1	2
NFKBIA	0.012	0.036	-10000	0	-0.81	1	1
BIRC3	-0.023	0.17	-10000	0	-0.81	23	23
BAX	-0.003	0.021	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.009	-10000	0	-10000	0	0
BAD	-0.013	0.041	0.21	5	-10000	0	5
SMPD1	0.018	0.053	-10000	0	-0.25	4	4
RB1	-0.014	0.046	0.23	1	-0.36	2	3
FADD/Caspase 8	-0.013	0.17	-10000	0	-0.6	8	8
MAP2K4	-0.005	0.039	-10000	0	-10000	0	0
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.005	0.039	-10000	0	-10000	0	0
EGF	-0.1	0.24	-10000	0	-0.58	101	101
mol:ceramide	-0.024	0.044	0.22	5	-10000	0	5
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.069	-10000	0	-0.62	6	6
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.015	0.046	0.22	2	-0.35	2	4
cell proliferation	-0.047	0.093	-10000	0	-0.39	4	4
BID	0.02	0.058	-10000	0	-10000	0	0
MAP3K1	-0.013	0.041	0.21	5	-10000	0	5
EIF2A	0	0.05	-10000	0	-0.44	3	3
TRADD	0.014	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.007	0.037	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.007	0.037	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.014	0.04	0.21	1	-10000	0	1
FADD	-0.027	0.18	-10000	0	-0.45	68	68
KSR1	-0.013	0.041	0.21	5	-10000	0	5
MAPK8	-0.003	0.05	0.22	1	-0.3	3	4
PRKRA	-0.013	0.041	0.21	5	-10000	0	5
PDGFA	0.004	0.088	-10000	0	-0.81	6	6
TRAF2	0.004	0.088	-10000	0	-0.81	6	6
IGF1	-0.086	0.22	-10000	0	-0.59	86	86
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.024	0.044	0.22	5	-10000	0	5
CTSD	0.014	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.03	0.11	-10000	0	-0.42	4	4
PRKCD	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.026	-10000	0	-0.58	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.069	-10000	0	-0.62	6	6
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.022	0.085	-10000	0	-0.44	9	9
TNFR1A/BAG4/TNF-alpha	-0.025	0.11	-10000	0	-0.53	21	21
mol:Sphingosine-1-phosphate	0.017	0.068	-10000	0	-0.62	6	6
MAP2K1	0.003	0.037	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	-0.004	0.035	0.32	1	-10000	0	1
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.002	0.026	-10000	0	-0.42	2	2
EIF2AK2	-0.008	0.052	-10000	0	-0.46	3	3
TNF-alpha/TNFR1A/FAN	-0.024	0.11	-10000	0	-0.53	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.034	0.048	-10000	0	-10000	0	0
MAP2K2	0.003	0.037	-10000	0	-10000	0	0
SMPD3	0.001	0.1	-10000	0	-0.33	34	34
TNF	-0.024	0.17	-10000	0	-0.77	25	25
PKC zeta/PAR4	-0.001	0.018	-10000	0	-0.42	1	1
mol:PHOSPHOCHOLINE	0.032	0.098	0.22	104	-10000	0	104
NF kappa B1/RelA/I kappa B alpha	-0.001	0.023	-10000	0	-0.45	1	1
AIFM1	-0.004	0.035	0.2	4	-10000	0	4
BCL2	0.002	0.092	-10000	0	-0.68	9	9

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.011	0.037	-9999	-0.58	2	2
Caspase 8 (4 units)	-0.034	0.075	-9999	-0.47	4	4
NEF	-0.007	0.046	-9999	-10000	0	0
NFKBIA	0.01	0.044	-9999	-0.8	1	1
BIRC3	0.012	0.16	-9999	-0.74	23	23
CYCS	0.007	0.11	-9999	-0.48	6	6
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.027	0.18	-9999	-0.88	21	21
MAP2K7	0.01	0.095	-9999	-0.44	4	4
protein ubiquitination	0.03	0.098	-9999	-0.44	2	2
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	0.011	0.037	-9999	-0.58	2	2
BID	-0.001	0.11	-9999	-0.5	7	7
NF-kappa-B/RelA/I kappa B alpha	-0.015	0.069	-9999	-0.52	1	1
TRADD	0.014	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
CFLAR	0.014	0	-9999	-10000	0	0
FADD	-0.081	0.26	-9999	-0.81	60	60
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.015	0.07	-9999	-0.52	1	1
MAPK8	0.014	0.098	-9999	-0.44	5	5
APAF1	0.012	0.026	-9999	-0.58	1	1
TRAF1	-0.007	0.13	-9999	-0.81	13	13
TRAF2	0.004	0.088	-9999	-0.81	6	6
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.008	0.11	-9999	-0.5	6	6
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.013	0.12	-9999	-0.46	9	9
CHUK	0.029	0.1	-9999	-0.48	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.053	0.15	-9999	-0.46	60	60
TCRz/NEF	-0.048	0.17	-9999	-0.52	48	48
TNF	-0.024	0.17	-9999	-0.77	25	25
FASLG	-0.046	0.25	-9999	-0.8	47	47
NFKB1	0.012	0.025	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.025	0.11	-9999	-0.53	21	21
CASP6	-0.02	0.047	-9999	-10000	0	0
CASP7	0.037	0.12	-9999	-0.5	4	4
RELA	0.012	0.025	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.037	0.12	-9999	-0.5	4	4
TNFRSF1A	0.014	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.002	0.026	-9999	-0.42	2	2
CASP8	0.014	0	-9999	-10000	0	0
CASP9	0.014	0	-9999	-10000	0	0
MAP3K14	0.022	0.11	-9999	-0.49	4	4
APAF-1/Caspase 9	-0.04	0.1	-9999	-0.5	5	5
BCL2	0.016	0.11	-9999	-0.46	5	5

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	-0.006	0.058	-9999	-0.54	6	6
ATM	0.012	0.026	-9999	-0.58	1	1
MAP2K3	0.015	0.049	-9999	-0.34	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.017	0.067	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.003	0.088	-9999	-0.69	8	8
TXN	0.009	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
GADD45A	0.012	0.036	-9999	-0.81	1	1
GADD45B	0.014	0	-9999	-10000	0	0
MAP3K1	0.014	0	-9999	-10000	0	0
MAP3K6	0.012	0.026	-9999	-0.58	1	1
MAP3K7	0.014	0	-9999	-10000	0	0
MAP3K4	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.018	-9999	-0.42	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	-0.008	0.061	-9999	-0.49	8	8
TRAF2	0.004	0.088	-9999	-0.81	6	6
RAC1/OSM/MEKK3/MKK3	-0.012	0.048	-9999	-0.42	3	3
TRAF6	0.009	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.16	0.27	-9999	-0.58	146	146
CCM2	0.001	0.1	-9999	-0.81	8	8
CaM/Ca2+/CAMKIIB	-0.1	0.16	-9999	-0.36	146	146
MAPK11	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.09	0.14	-9999	-0.49	5	5
OSM/MEKK3	-0.01	0.076	-9999	-0.62	8	8
TAOK1	0.009	0.057	-9999	-0.35	13	13
TAOK2	0.018	0.016	-9999	-0.35	1	1
TAOK3	0.018	0.016	-9999	-0.35	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.014	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAP3K10	0.014	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
TRX/ASK1	0.017	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.007	0.051	-9999	-0.46	5	5

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0.036	-9999	-0.81	1	1
ITGB7	0.011	0.037	-9999	-0.58	2	2
ITGA4	-0.004	0.12	-9999	-0.81	11	11
alpha4/beta7 Integrin	-0.015	0.092	-9999	-0.59	13	13
alpha4/beta1 Integrin	-0.014	0.093	-9999	-0.62	12	12

×

Arf6 downstream 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
PLAUR	0.007	0.16	-10000	0	-0.64	29	29
regulation of axonogenesis	-0.02	0.037	-10000	0	-10000	0	0
myoblast fusion	0.007	0.085	0.32	29	-10000	0	29
mol:GTP	-0.014	0.045	-10000	0	-0.25	3	3
regulation of calcium-dependent cell-cell adhesion	-0.018	0.063	0.4	3	-10000	0	3
ARF1/GTP	-0.008	0.03	-10000	0	-10000	0	0
mol:GM1	0	0.036	-10000	0	-0.19	3	3
mol:Choline	0.019	0.042	-10000	0	-0.35	3	3
lamellipodium assembly	-0.025	0.078	-10000	0	-0.32	29	29
MAPK3	0.013	0.067	-10000	0	-0.3	3	3
ARF6/GTP/NME1/Tiam1	0.019	0.064	-10000	0	-0.4	3	3
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.085	-10000	0	-0.32	29	29
ARF1/GDP	0.003	0.079	-10000	0	-0.49	3	3
ARF6	0.005	0.026	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.008	0.063	-10000	0	-0.57	6	6
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.067	-10000	0	-0.3	3	3
actin filament bundle formation	0.022	0.07	0.48	3	-10000	0	3
KALRN	-0.039	0.1	-10000	0	-0.33	43	43
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.023	0.07	-10000	0	-0.49	3	3
NME1	0.013	0.036	-10000	0	-0.8	1	1
Rac1/GDP	-0.023	0.07	-10000	0	-0.49	3	3
substrate adhesion-dependent cell spreading	-0.014	0.045	-10000	0	-0.25	3	3
cortical actin cytoskeleton organization	-0.025	0.079	-10000	0	-0.32	29	29
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.014	0.045	-10000	0	-0.25	3	3
ARF6/GTP	-0.014	0.045	-10000	0	-0.25	3	3
RhoA/GTP	-0.008	0.03	-10000	0	-10000	0	0
mol:GDP	-0.025	0.08	-10000	0	-0.32	29	29
ARF6/GTP/RAB11FIP3/RAB11A	-0.005	0.024	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	0.009	0.048	-10000	0	-0.4	3	3
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.025	0.078	-10000	0	-0.32	29	29
ruffle organization	0.02	0.037	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.014	0.045	-10000	0	-0.25	3	3
PLD2	0.012	0.036	-10000	0	-10000	0	0
PIP5K1A	0.021	0.037	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.019	0.042	-10000	0	-0.35	3	3
Rac1/GTP	-0.025	0.079	-10000	0	-0.32	29	29

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.012	0.036	-10000	0	-0.81	1	1
Rac1/GDP	0.002	0.01	-10000	0	-10000	0	0
DOCK1	0.011	0.037	-10000	0	-0.58	2	2
ITGA4	-0.004	0.12	-10000	0	-0.81	11	11
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.015	0.092	-10000	0	-0.59	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.012	0.08	-10000	0	-0.53	12	12
alpha4/beta7 Integrin/Paxillin	-0.011	0.072	-10000	0	-0.48	11	11
lamellipodium assembly	-0.001	0.03	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
PI3K	-0.002	0.026	-10000	0	-0.42	2	2
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.01	0.051	-10000	0	-0.81	2	2
PXN	0.024	0	-10000	0	-10000	0	0
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
ARF6/GTP	-0.009	0.062	-10000	0	-0.41	12	12
cell adhesion	-0.012	0.072	-10000	0	-0.45	14	14
CRKL/CBL	-0.001	0.027	-10000	0	-0.62	1	1
alpha4/beta1 Integrin/Paxillin	-0.011	0.073	-10000	0	-0.48	12	12
ITGB1	0.012	0.036	-10000	0	-0.81	1	1
ITGB7	0.011	0.037	-10000	0	-0.58	2	2
ARF6/GDP	0.002	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.052	0.15	-10000	0	-0.47	52	52
p130Cas/Crk/Dock1	-0.001	0.021	-10000	0	-10000	0	0
VCAM1	-0.063	0.23	-10000	0	-0.77	51	51
alpha4/beta1 Integrin/Paxillin/Talin	-0.012	0.073	-10000	0	-0.45	14	14
alpha4/beta1 Integrin/Paxillin/GIT1	-0.01	0.068	-10000	0	-0.45	12	12
BCAR1	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.067	0.45	12	-10000	0	12
CBL	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GIT1	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.012	0.073	-10000	0	-0.45	14	14
Rac1/GTP	-0.001	0.033	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	-0.004	0.084	0.71	7	-10000	0	7
PI3K Class IB/PDE3B	0.004	0.084	-10000	0	-0.71	7	7
PDE3B	0.004	0.084	-10000	0	-0.71	7	7

×

BARD1 signaling events

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
BARD1/CSTF1	-0.025	0.098	-10000	0	-0.42	31	31
ATM	0.012	0.026	-10000	0	-0.58	1	1
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.027	0.016	-10000	0	-0.34	1	1
protein ubiquitination	-0.023	0.089	-10000	0	-0.53	7	7
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.005	0.04	-10000	0	-0.56	1	1
FANCF	0.009	0.052	-10000	0	-0.58	4	4
BRCA1	0.014	0	-10000	0	-10000	0	0
CCNE1	0.002	0.095	-10000	0	-0.81	7	7
CDK2/Cyclin E1	-0.008	0.071	-10000	0	-0.62	7	7
FANCG	0.007	0.072	-10000	0	-0.81	4	4
BRCA1/BACH1/BARD1	-0.025	0.098	-10000	0	-0.42	31	31
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.014	0	-10000	0	-10000	0	0
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	0.01	0.051	-10000	0	-0.81	2	2
DNA repair	0.055	0.094	-10000	0	-0.76	2	2
BRCA1/BARD1/ubiquitin	-0.025	0.098	-10000	0	-0.42	31	31
BARD1/DNA-PK	-0.018	0.072	-10000	0	-10000	0	0
FANCL	0.012	0.036	-10000	0	-0.81	1	1
mRNA polyadenylation	0.025	0.098	0.41	31	-10000	0	31
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.068	-10000	0	-0.4	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.022	0.085	-10000	0	-0.53	1	1
BRCA1/BARD1/P53	-0.021	0.077	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.021	0.082	-10000	0	-10000	0	0
BRCA1/BACH1	0.014	0	-10000	0	-10000	0	0
BARD1	-0.022	0.14	-10000	0	-0.58	31	31
PCNA	0.012	0.036	-10000	0	-0.81	1	1
BRCA1/BARD1/UbcH5C	-0.021	0.082	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	-0.021	0.082	-10000	0	-0.34	31	31
BRCA1/BARD1/RAD51/PCNA	-0.021	0.091	-10000	0	-0.86	2	2
BARD1/DNA-PK/P53	-0.019	0.07	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.025	0.098	-10000	0	-0.42	31	31
BRCA1/BARD1/CTIP	-0.019	0.073	-10000	0	-10000	0	0
FA complex	0.037	0.042	-10000	0	-0.5	1	1
BARD1/EWS	-0.025	0.098	-10000	0	-0.42	31	31
RBBP8	0.023	0.019	-10000	0	-0.42	1	1
TP53	0.009	0.052	-10000	0	-0.58	4	4
TOPBP1	0.012	0.036	-10000	0	-0.81	1	1
G1/S transition of mitotic cell cycle	0.02	0.076	-10000	0	-10000	0	0
BRCA1/BARD1	-0.023	0.09	-10000	0	-0.53	7	7
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.025	0.1	-10000	0	-0.42	31	31
CDK2	0.014	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.01	0.051	-10000	0	-0.81	2	2
RAD50	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.025	0.098	-10000	0	-0.42	31	31
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.052	-9999	-0.53	1	1
BIRC5	-0.021	0.16	-9999	-0.81	22	22
NFKBIA	0.024	0.053	-9999	-0.53	1	1
CPEB1	-0.074	0.22	-9999	-0.62	71	71
AKT1	0.025	0.047	-9999	-10000	0	0
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.005	0.038	-9999	-10000	0	0
NDEL1/TACC3	-0.006	0.045	-9999	-0.46	2	2
GADD45A	0.012	0.036	-9999	-0.81	1	1
GSK3B	0.013	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.02	0.052	-9999	-0.53	1	1
MDM2	0.014	0	-9999	-10000	0	0
JUB	0.012	0.026	-9999	-0.58	1	1
TPX2	0.012	0.088	-9999	-0.62	10	10
TP53	0.024	0.042	-9999	-0.31	4	4
DLG7	0.014	0.046	-9999	-0.29	11	11
AURKAIP1	0.012	0.036	-9999	-0.81	1	1
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.006	0.048	-9999	-0.48	2	2
G2/M transition of mitotic cell cycle	-0.005	0.038	-9999	-10000	0	0
AURKA	0.017	0.055	-9999	-0.34	11	11
AURKB	-0.007	0.042	-9999	-0.28	10	10
CDC25B	0.012	0.082	-9999	-0.34	22	22
G2/M transition checkpoint	-0.005	0.044	-9999	-0.55	1	1
mRNA polyadenylation	-0.052	0.13	-9999	-0.36	70	70
Aurora A/CPEB	-0.053	0.13	-9999	-0.36	70	70
Aurora A/TACC1/TRAP/chTOG	-0.005	0.038	-9999	-10000	0	0
BRCA1	0.014	0	-9999	-10000	0	0
centrosome duplication	0.02	0.052	-9999	-0.53	1	1
regulation of centrosome cycle	-0.006	0.044	-9999	-0.45	2	2
spindle assembly	-0.005	0.038	-9999	-10000	0	0
TDRD7	0.014	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.024	0.1	-9999	-0.49	22	22
CENPA	-0.008	0.045	-9999	-0.37	6	6
Aurora A/PP2A	0.021	0.046	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.031	0.042	-9999	-10000	0	0
negative regulation of DNA binding	0.024	0.042	-9999	-0.31	4	4
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.58	2	2
Ajuba/Aurora A	-0.005	0.044	-9999	-0.55	1	1
mitotic prometaphase	0.001	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.055	-9999	-0.34	11	11
TACC1	0.011	0.037	-9999	-0.58	2	2
TACC3	0.01	0.051	-9999	-0.81	2	2
Aurora A/Antizyme1	-0.005	0.043	-9999	-0.48	1	1
Aurora A/RasGAP	0.019	0.051	-9999	-0.35	2	2
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.023	-9999	-0.53	1	1
Importin alpha/Importin beta/TPX2	0.012	0.088	-9999	-0.62	10	10
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	0.02	0.087	-9999	-0.53	10	10
PAK1	0.012	0.036	-9999	-0.81	1	1
CKAP5	0.014	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.008	0.096	-10000	0	-0.68	10	10
oxygen homeostasis	-0.002	0.017	-10000	0	-10000	0	0
TCEB2	0.01	0.051	-10000	0	-0.81	2	2
TCEB1	0.012	0.036	-10000	0	-0.81	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.024	0.081	-10000	0	-0.59	2	2
EPO	-0.048	0.28	-10000	0	-0.73	34	34
FIH (dimer)	0.011	0.016	-10000	0	-10000	0	0
APEX1	0.014	0.015	-10000	0	-10000	0	0
SERPINE1	-0.25	0.39	-10000	0	-0.83	52	52
FLT1	0.005	0.044	-10000	0	-10000	0	0
ADORA2A	-0.025	0.24	-10000	0	-0.8	8	8
germ cell development	-0.044	0.27	-10000	0	-0.82	21	21
SLC11A2	-0.021	0.23	-10000	0	-0.87	5	5
BHLHE40	-0.023	0.24	-10000	0	-0.88	6	6
HIF1AN	0.011	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.064	0.1	-10000	0	-0.58	2	2
ETS1	0.025	0.063	-10000	0	-0.8	3	3
CITED2	0	0.058	-10000	0	-1.2	1	1
KDR	0.002	0.087	-10000	0	-1.3	2	2
PGK1	-0.021	0.23	-10000	0	-0.87	5	5
SIRT1	0.012	0.026	-10000	0	-0.58	1	1
response to hypoxia	-0.001	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.033	0.27	-10000	0	-1	7	7
EPAS1	0.005	0.13	-10000	0	-0.44	7	7
SP1	0.022	0.003	-10000	0	-10000	0	0
ABCG2	-0.028	0.25	-10000	0	-0.84	10	10
EFNA1	-0.022	0.24	-10000	0	-0.92	5	5
FXN	-0.022	0.23	-10000	0	-0.82	6	6
POU5F1	-0.048	0.28	-10000	0	-0.87	21	21
neuron apoptosis	0.032	0.26	0.96	7	-10000	0	7
EP300	0.012	0.026	-10000	0	-0.58	1	1
EGLN3	-0.039	0.2	-10000	0	-0.78	33	33
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.011	0.016	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.003	0.04	-10000	0	-0.53	3	3
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.014	0.015	-10000	0	-10000	0	0
SLC2A1	-0.031	0.26	-10000	0	-0.86	14	14
TWIST1	-0.034	0.26	-10000	0	-0.85	18	18
ELK1	0.02	0.036	-10000	0	-0.8	1	1
HIF2A/ARNT/Cbp/p300	-0.053	0.096	-10000	0	-0.57	2	2
VEGFA	-0.026	0.25	-10000	0	-0.92	10	10
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.028	0.12	-9999	-0.57	25	25
AKT1	0.085	0.059	-9999	-0.51	2	2
PTK2B	0.031	0.12	-9999	-0.65	3	3
VEGFR2 homodimer/Frs2	0.031	0.067	-9999	-0.58	6	6
CAV1	-0.046	0.21	-9999	-0.81	38	38
CALM1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.013	0.078	-9999	-0.5	13	13
endothelial cell proliferation	0.094	0.064	-9999	-0.46	2	2
mol:Ca2+	0.051	0.069	-9999	-0.58	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.008	0.063	-9999	-0.6	2	2
RP11-342D11.1	0.042	0.069	-9999	-0.58	2	2
CDH5	0.011	0.044	-9999	-0.69	2	2
VEGFA homodimer	-0.007	0.057	-9999	-0.48	7	7
SHC1	0.014	0	-9999	-10000	0	0
SHC2	0.004	0.084	-9999	-0.71	7	7
HRAS/GDP	-0.008	0.054	-9999	-10000	0	0
SH2D2A	-0.11	0.3	-9999	-0.81	81	81
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.008	0.048	-9999	-0.47	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.082	0.19	-9999	-0.49	88	88
VEGFR1 homodimer	0.012	0.036	-9999	-0.81	1	1
SHC/GRB2/SOS1	-0.008	0.056	-9999	-0.54	2	2
GRB10	0.051	0.075	-9999	-0.62	3	3
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PAK1	0.012	0.036	-9999	-0.81	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.01	0.064	-9999	-0.58	2	2
HRAS	0.012	0.036	-9999	-0.81	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.039	0.066	-9999	-0.5	2	2
HIF1A	0.012	0.026	-9999	-0.58	1	1
FRS2	0.007	0.072	-9999	-0.81	4	4
oxygen and reactive oxygen species metabolic process	-0.008	0.062	-9999	-0.6	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.003	0.091	-9999	-0.77	7	7
Nck/Pak	-0.001	0.027	-9999	-0.62	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.01	0.07	-9999	-0.64	2	2
mol:GDP	-0.008	0.055	-9999	-0.53	2	2
mol:NADP	0.073	0.058	-9999	-10000	0	0
eNOS/Hsp90	0.076	0.056	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
mol:IP3	0.052	0.07	-9999	-0.58	2	2
HIF1A/ARNT	-0.001	0.018	-9999	-0.42	1	1
SHB	0.011	0.037	-9999	-0.58	2	2
VEGFA	0.005	0.094	-9999	-0.8	7	7
VEGFC	-0.1	0.29	-9999	-0.8	74	74
FAK1/Vinculin	0.057	0.09	-9999	-0.71	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.028	0.11	-9999	-0.69	3	3
PTPN6	0.014	0	-9999	-10000	0	0
EPAS1	0.023	0.023	-9999	-10000	0	0
mol:L-citrulline	0.073	0.058	-9999	-10000	0	0
ITGAV	0.006	0.076	-9999	-0.76	5	5
PIK3CA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.012	0.073	-9999	-0.6	2	2
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.067	-9999	-0.64	2	2
VEGFR2/3 heterodimer	0.029	0.077	-9999	-0.57	8	8
VEGFB	0.012	0.036	-9999	-0.81	1	1
MAPK11	0.054	0.07	-9999	-0.6	2	2
VEGFR2 homodimer	0.035	0.052	-9999	-0.79	2	2
FLT1	0.012	0.036	-9999	-0.81	1	1
NEDD4	0.016	0.003	-9999	-10000	0	0
MAPK3	0.056	0.068	-9999	-0.53	2	2
MAPK1	0.056	0.068	-9999	-0.53	2	2
VEGFA145/NRP2	-0.011	0.08	-9999	-0.61	9	9
VEGFR1/2 heterodimer	0.035	0.052	-9999	-0.64	3	3
KDR	0.035	0.052	-9999	-0.8	2	2
VEGFA165/NRP1/VEGFR2 homodimer	0.048	0.074	-9999	-0.58	2	2
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.058	0.068	-9999	-0.54	2	2
PI3K	-0.008	0.053	-9999	-0.58	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.009	0.067	-9999	-0.51	9	9
FES	0.052	0.071	-9999	-0.59	2	2
GAB1	-0.008	0.055	-9999	-0.6	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.067	-9999	-0.51	9	9
CTNNB1	0.012	0.026	-9999	-0.58	1	1
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.047	0.12	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.009	0.067	-9999	-0.51	9	9
PI3K/GAB1	0.086	0.061	-9999	-0.52	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.012	0.071	-9999	-0.58	2	2
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.076	0.18	-9999	-0.5	78	78
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.052	0.071	-9999	-0.59	2	2
actin cytoskeleton reorganization	-0.082	0.18	-9999	-0.48	88	88
PTK2	0.052	0.095	-9999	-0.77	2	2
EDG1	0.042	0.069	-9999	-0.58	2	2
mol:DAG	0.052	0.07	-9999	-0.58	2	2
CaM/Ca2+	-0.008	0.056	-9999	-0.53	2	2
MAP2K3	0.054	0.077	-9999	-0.56	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.05	0.077	-9999	-0.64	3	3
PLCG1	0.052	0.071	-9999	-0.59	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.009	0.065	-9999	-0.6	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.009	0.067	-9999	-0.51	9	9
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.009	0.067	-9999	-0.51	9	9
cell migration	0.08	0.08	-9999	-0.59	2	2
mol:PI-3-4-5-P3	0.072	0.063	-9999	-0.54	2	2
FYN	0.012	0.036	-9999	-0.81	1	1
VEGFB/NRP1	0.047	0.069	-9999	-0.55	2	2
mol:NO	0.073	0.058	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.053	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.051	0.077	-9999	-0.64	3	3
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.017	0.15	-9999	-0.73	21	21
NOS3	0.075	0.063	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.014	0.083	-9999	-0.51	13	13
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.057	0.07	-9999	-0.54	2	2
PRKCB	0.051	0.085	-9999	-0.54	2	2
VCL	0.014	0	-9999	-10000	0	0
VEGFA165/NRP1	0.042	0.07	-9999	-0.47	9	9
VEGFR1/2 heterodimer/VEGFA homodimer	-0.01	0.07	-9999	-0.5	10	10
VEGFA165/NRP2	-0.011	0.08	-9999	-0.61	9	9
MAPKKK cascade	0.072	0.069	-9999	-0.58	1	1
NRP2	0.01	0.051	-9999	-0.81	2	2
VEGFC homodimer	-0.1	0.28	-9999	-0.8	74	74
NCK1	0.014	0	-9999	-10000	0	0
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.057	0.09	-9999	-0.71	2	2
MAP3K13	0.047	0.079	-9999	-0.59	2	2
PDPK1	0.077	0.059	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.011	0.045	-9999	-0.58	3	3
ELF1	-0.012	0.11	-9999	-0.56	4	4
CCNA2	0.012	0.036	-9999	-0.81	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
JAK3	-0.02	0.16	-9999	-0.81	22	22
PIK3R1	0.012	0.037	-9999	-0.58	2	2
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.043	0.11	-9999	-0.58	8	8
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.017	0.043	-9999	-10000	0	0
IL2RA	-0.036	0.22	-9999	-0.71	47	47
IL2RB	0.002	0.098	-9999	-0.78	8	8
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.012	0.14	-9999	-0.78	17	17
G1/S transition of mitotic cell cycle	0.032	0.089	-9999	-0.61	5	5
PTPN11	0.014	0	-9999	-10000	0	0
CCND2	0.021	0.097	-9999	-0.76	8	8
LCK	-0.005	0.12	-9999	-0.81	12	12
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.004	0.036	-9999	-0.81	1	1
CDK6	0.001	0.098	-9999	-0.78	8	8
CCND3	0.051	0.098	-9999	-0.59	3	3

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.048	0.11	-9999	-0.61	4	4
TC10/GTP	-0.043	0.098	-9999	-0.68	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.004	0.039	-9999	-0.45	2	2
HRAS	0.012	0.036	-9999	-0.81	1	1
APS homodimer	0.01	0.051	-9999	-0.81	2	2
GRB14	-0.045	0.18	-9999	-0.61	48	48
FOXO3	-0.007	0.042	-9999	-0.64	2	2
AKT1	0.022	0.098	-9999	-10000	0	0
INSR	0.014	0.026	-9999	-0.57	1	1
Insulin Receptor/Insulin	0.036	0.03	-9999	-0.4	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0.036	-9999	-0.81	1	1
SORBS1	-0.084	0.22	-9999	-0.58	86	86
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.035	0.029	-9999	-0.39	2	2
CAV1	-0.012	0.14	-9999	-0.47	40	40
CBL/APS/CAP/Crk-II/C3G	-0.048	0.11	-9999	-0.6	2	2
Insulin Receptor/Insulin/IRS1/NCK2	-0.004	0.039	-9999	-0.45	2	2
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.037	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.036	-9999	-0.5	1	1
RPS6KB1	0.029	0.092	-9999	-10000	0	0
PARD6A	0.011	0.044	-9999	-0.69	2	2
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.02	-9999	-0.44	1	1
PIK3R1	0.011	0.037	-9999	-0.58	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.024	0.072	-9999	-10000	0	0
HRAS/GTP	-0.005	0.035	-9999	-10000	0	0
Insulin Receptor	0.014	0.026	-9999	-0.57	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.004	0.036	-9999	-10000	0	0
PRKCI	-0.007	0.02	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.089	-9999	-0.52	2	2
SHC1	0.014	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.001	0.024	-9999	-10000	0	0
PI3K	-0.005	0.038	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.001	0.027	-9999	-0.63	1	1
AKT2	0.022	0.098	-9999	-10000	0	0
PRKCZ	-0.008	0.029	-9999	-0.48	1	1
SH2B2	0.01	0.051	-9999	-0.81	2	2
SHC/SHIP	0.031	0.042	-9999	-10000	0	0
F2RL2	-0.2	0.36	-9999	-0.8	137	137
TRIP10	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.002	0.031	-9999	-0.46	2	2
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.002	0.028	-9999	-0.42	2	2
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.58	2	2
NCK1	0.014	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.052	0.12	-9999	-0.64	2	2
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.003	0.038	-9999	-0.47	3	3
INPP5D	0.024	0.044	-9999	-0.42	2	2
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.005	0.057	-9999	-0.91	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.58	3	3
p62DOK/RasGAP	-0.001	0.025	-9999	-10000	0	0
INS	0.001	0.05	-9999	-0.8	2	2
mol:PI-3-4-P2	0.024	0.044	-9999	-0.42	2	2
GRB2	0.014	0	-9999	-10000	0	0
EIF4EBP1	0.022	0.11	-9999	-0.61	1	1
PTPRA	0.015	0.003	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.012	0.026	-9999	-0.58	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.033	0.03	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.04	-9999	-0.46	2	2
Insulin Receptor/Insulin/IRS3	-0.003	0.042	-9999	-0.55	3	3
Par3/Par6	-0.12	0.2	-9999	-0.46	136	136

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.067	-9999	-0.75	4	4
CDC42/GTP	-0.021	0.069	-9999	-0.48	3	3
PLCG1	0.018	0.084	-9999	-0.5	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.005	0.054	-9999	-0.62	4	4
cell migration	-0.021	0.068	-9999	-0.47	3	3
S1PR5	0.008	0.062	-9999	-0.69	4	4
S1PR4	-0.032	0.19	-9999	-0.8	29	29
MAPK3	0.018	0.084	-9999	-0.5	3	3
MAPK1	0.018	0.084	-9999	-0.5	3	3
S1P/S1P5/Gi	0.024	0.059	-9999	-0.48	1	1
GNAI1	0.012	0.026	-9999	-0.58	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.008	0.062	-9999	-0.49	8	8
RHOA	0.003	0.12	-9999	-0.46	32	32
S1P/S1P4/Gi	0.009	0.088	-9999	-0.53	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.014	0.14	-9999	-0.74	19	19
S1P/S1P4/G12/G13	-0.031	0.12	-9999	-0.49	32	32
GNA12	0.007	0.072	-9999	-0.81	4	4
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.006	0.06	-9999	-0.55	6	6
CRKL	0.029	0.059	-9999	-0.43	1	1
mol:PIP3	-0.023	0.004	-9999	-10000	0	0
AKT1	0	0.014	-9999	-10000	0	0
PTK2B	0.012	0.026	-9999	-0.58	1	1
RAPGEF1	0.036	0.056	-9999	-0.4	1	1
RANBP10	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.023	0.097	-9999	-0.53	11	11
MAP3K5	0.04	0.06	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.022	0.092	-9999	-0.48	13	13
AP1	-0.031	0.13	-9999	-0.37	67	67
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.07	0.24	-9999	-0.7	67	67
STAT3 (dimer)	0.029	0.067	-9999	-0.48	1	1
GAB1/CRKL/SHP2/PI3K	-0.01	0.045	-9999	-0.43	1	1
INPP5D	0.011	0.037	-9999	-0.58	2	2
CBL/CRK	0.036	0.053	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0
ELK1	-0.001	0.028	-9999	-0.26	6	6
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.032	-9999	-10000	0	0
PAK1	0.007	0.025	-9999	-0.47	1	1
HGF/MET/RANBP10	-0.023	0.097	-9999	-0.53	11	11
HRAS	0.022	0.083	-9999	-0.61	2	2
DOCK1	0.034	0.059	-9999	-0.4	1	1
GAB1	0.023	0.058	-9999	-0.27	3	3
CRK	0.03	0.055	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.094	-9999	-0.48	17	17
JUN	0.014	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	0.004	0.054	-9999	-0.22	28	28
PIK3R1	0.011	0.037	-9999	-0.58	2	2
cell morphogenesis	0.058	0.072	-9999	-0.45	1	1
GRB2/SHC	0.02	0.048	-9999	-10000	0	0
FOS	-0.063	0.2	-9999	-0.58	67	67
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.001	0.028	-9999	-0.25	6	6
HGF/MET/MUC20	-0.023	0.099	-9999	-0.43	28	28
cell migration	0.02	0.047	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
MET/RANBP10	-0.006	0.06	-9999	-0.55	6	6
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.023	0.07	-9999	-0.52	1	1
MET/MUC20	-0.006	0.061	-9999	-0.56	6	6
RAP1B	0.041	0.057	-9999	-0.38	2	2
RAP1A	0.042	0.054	-9999	-10000	0	0
HGF/MET/RANBP9	-0.023	0.097	-9999	-0.53	11	11
RAF1	0.03	0.079	-9999	-0.56	2	2
STAT3	0.03	0.067	-9999	-0.49	1	1
cell proliferation	0.039	0.083	-9999	-0.44	1	1
RPS6KB1	0.01	0.021	-9999	-10000	0	0
MAPK3	-0.007	0.026	-9999	-0.26	4	4
MAPK1	-0.007	0.026	-9999	-0.26	4	4
RANBP9	0.014	0	-9999	-10000	0	0
MAPK8	0.05	0.079	-9999	-0.46	7	7
SRC	0.03	0.066	-9999	-0.48	1	1
PI3K	0.019	0.053	-9999	-0.46	1	1
MET/Glomulin	0.007	0.056	-9999	-0.5	6	6
SOS1	0.014	0	-9999	-10000	0	0
MAP2K1	0.037	0.075	-9999	-0.52	2	2
MET	0.005	0.08	-9999	-0.73	6	6
MAP4K1	0.033	0.063	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
MAP2K2	0.037	0.075	-9999	-0.52	2	2
BAD	0.007	0.013	-9999	-10000	0	0
MAP2K4	0.046	0.057	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.048	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
SH3KBP1	0.01	0.051	-9999	-0.81	2	2
HGS	0.013	0.05	-9999	-10000	0	0
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.015	0.14	-9999	-0.65	22	22
RASA1	0.011	0.037	-9999	-0.58	2	2
NCK1	0.014	0	-9999	-10000	0	0
PTPRJ	0.014	0	-9999	-10000	0	0
NCK/PLCgamma1	0.021	0.052	-9999	-10000	0	0
PDPK1	-0.011	0.015	-9999	-0.34	1	1
HGF/MET/SHIP	-0.024	0.1	-9999	-0.54	12	12

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.13	-9999	-0.58	26	26
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.019	0.044	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.012	0.036	-9999	-0.81	1	1
MAP3K12	0.011	0.044	-9999	-0.69	2	2
FGR	0.012	0.036	-9999	-0.81	1	1
p38 alpha/TAB1	-0.017	0.04	-9999	-10000	0	0
PRKG1	-0.024	0.15	-9999	-0.64	30	30
DUSP8	0.014	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.031	0.078	-9999	-0.39	14	14
apoptosis	-0.017	0.038	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.012	0.036	-9999	-0.81	1	1
DUSP1	-0.017	0.13	-9999	-0.58	27	27
PAK1	0.012	0.036	-9999	-0.81	1	1
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.061	-9999	-0.48	8	8
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.001	0.1	-9999	-0.81	8	8
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.024	0.092	-9999	-0.37	4	4
BLK	-0.1	0.28	-9999	-0.77	75	75
HCK	0.006	0.076	-9999	-0.76	5	5
MAP2K3	0.012	0.026	-9999	-0.58	1	1
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	0.012	0.036	-9999	-0.81	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.032	0.066	-9999	-10000	0	0
positive regulation of innate immune response	0.032	0.099	-9999	-0.4	1	1
LCK	-0.005	0.12	-9999	-0.81	12	12
p38alpha-beta/MKP7	0.038	0.095	-9999	-10000	0	0
p38alpha-beta/MKP5	0.037	0.096	-9999	-10000	0	0
PGK/cGMP	-0.028	0.11	-9999	-0.48	30	30
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.024	0.12	-9999	-0.5	4	4
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.018	0.15	-9999	-0.81	18	18

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.014	0.07	-9999	-0.53	1	1
forebrain development	-0.023	0.16	-9999	-0.51	20	20
GNAO1	0.007	0.067	-9999	-0.75	4	4
SMO/beta Arrestin2	0.003	0.089	-9999	-0.42	21	21
SMO	-0.011	0.12	-9999	-0.59	21	21
ARRB2	0.013	0.005	-9999	-10000	0	0
GLI3/SPOP	0.055	0.036	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0.014	0	-9999	-10000	0	0
GNAI2	0.013	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0.005	0.026	-9999	-0.48	1	1
GNAI1	0.011	0.026	-9999	-0.58	1	1
XPO1	0.014	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.061	0.11	-9999	-0.52	9	9
SAP30	0.012	0.036	-9999	-0.81	1	1
mol:GDP	-0.011	0.12	-9999	-0.59	21	21
MIM/GLI2A	0.012	0.025	-9999	-10000	0	0
IFT88	0.014	0	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GLI2	0.023	0.066	-9999	-10000	0	0
GLI3	0.05	0.039	-9999	-10000	0	0
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0	-9999	-10000	0	0
GNG2	0.014	0	-9999	-10000	0	0
Gi family/GTP	0.014	0.086	-9999	-0.5	5	5
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.056	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.03	0.072	-9999	-10000	0	0
FOXA2	-0.094	0.23	-9999	-0.66	72	72
neural tube patterning	-0.023	0.16	-9999	-0.51	20	20
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.022	0.046	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
CSNK1G3	0.014	0	-9999	-10000	0	0
MTSS1	0.012	0.025	-9999	-10000	0	0
embryonic limb morphogenesis	-0.023	0.16	-9999	-0.51	20	20
SUFU	0.018	0.051	-9999	-0.41	1	1
LGALS3	0.011	0.037	-9999	-0.58	2	2
catabolic process	0.062	0.057	-9999	-10000	0	0
GLI3A/CBP	-0.024	0.11	-9999	-10000	0	0
KIF3A	0.014	0	-9999	-10000	0	0
GLI1	-0.024	0.16	-9999	-0.52	20	20
RAB23	0.01	0.051	-9999	-0.81	2	2
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	0.014	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.021	0.053	-9999	-0.49	1	1
GNAZ	-0.015	0.14	-9999	-0.74	19	19
RBBP4	0.012	0.026	-9999	-0.57	1	1
CSNK1G1	0.014	0	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.029	0.062	-9999	-10000	0	0
STK36	0.014	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.022	0.076	-9999	-0.43	5	5
PTCH1	-0.019	0.18	-9999	-1	7	7
MIM/GLI1	-0.039	0.21	-9999	-0.68	20	20
CREBBP	-0.024	0.11	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.05	0.02	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.015	0.088	-9999	-0.51	15	15
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.004	0.023	-9999	-10000	0	0
AURKB	-0.002	0.11	-9999	-0.81	10	10
AURKC	0.003	0.088	-9999	-0.74	7	7

×

Arf6 trafficking events

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
SLC2A4	-0.25	0.29	-10000	0	-0.58	233	233
CLTC	0.033	0.014	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.028	0.013	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.022	-10000	0	-0.49	1	1
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.03	0.01	-10000	0	-10000	0	0
CPE	0.013	0.06	-10000	0	-0.54	6	6
CTNNB1	0.012	0.026	-10000	0	-0.58	1	1
membrane fusion	0.027	0.014	-10000	0	-10000	0	0
CTNND1	0.033	0.021	-10000	0	-0.46	1	1
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.034	0.009	-10000	0	-10000	0	0
TSHR	0.004	0.088	-10000	0	-0.54	13	13
INS	0.012	0.017	-10000	0	-0.25	2	2
BIN1	-0.001	0.1	-10000	0	-0.74	10	10
mol:Choline	0.027	0.014	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.025	-10000	0	-0.54	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.021	-10000	0	-0.49	1	1
JUP	0.029	0.019	-10000	0	-0.28	1	1
ASAP2/amphiphysin II	-0.008	0.061	-10000	0	-0.49	7	7
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.027	0.028	-10000	0	-0.28	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.025	0.38	1	-10000	0	1
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.025	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.039	0.014	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.014	0	-10000	0	-10000	0	0
exocyst	0.046	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.033	0.021	-10000	0	-0.46	1	1
NME1	0.019	0.025	-10000	0	-0.54	1	1
clathrin coat assembly	0.033	0.014	-10000	0	-10000	0	0
IL2RA	0.008	0.072	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.11	0.12	-10000	0	-0.44	2	2
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.002	0.021	-10000	0	-0.28	3	3
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.034	0.009	-10000	0	-10000	0	0
SDC1	0.03	0.01	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.024	-10000	0	-0.54	1	1
EXOC7	0.014	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.003	0.025	-10000	0	-0.39	1	1
mol:Phosphatidic acid	0.027	0.014	-10000	0	-10000	0	0
endocytosis	0.008	0.061	0.49	7	-10000	0	7
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.017	0.084	-10000	0	-0.54	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.026	0.023	-10000	0	-0.49	1	1
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.024	0.068	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.023	-10000	0	-10000	0	0

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.011	0.007	-10000	0	-10000	0	0
BUB1B	0.021	0.025	-10000	0	-10000	0	0
PLK1	0.017	0.022	-10000	0	-0.16	1	1
PLK1S1	0.015	0.014	-10000	0	-0.17	1	1
KIF2A	0.024	0.019	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.017	0.022	-10000	0	-0.16	1	1
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.011	0.1	-10000	0	-0.47	21	21
WEE1	0.021	0.027	-10000	0	-10000	0	0
cytokinesis	0.03	0.032	-10000	0	-10000	0	0
PP2A-alpha B56	0.035	0.013	-10000	0	-10000	0	0
AURKA	0.012	0.032	-10000	0	-0.18	12	12
PICH/PLK1	0.023	0.085	-10000	0	-0.38	21	21
CENPE	0.024	0.019	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.024	0.019	-10000	0	-10000	0	0
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	0.012	0.029	-10000	0	-0.18	10	10
PAK1	0.011	0.036	-10000	0	-0.8	1	1
SPC24	-0.005	0.12	-10000	0	-0.81	12	12
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	0.012	0.032	-10000	0	-0.21	9	9
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.015	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.009	0.011	-10000	0	-0.071	1	1
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.013	12	12
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.008	-10000	0	-10000	0	0
spindle elongation	0.017	0.022	-10000	0	-0.16	1	1
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	-0.001	0.01	-10000	0	-10000	0	0
TPT1	0.015	0.011	-10000	0	-10000	0	0
CDC25C	0.009	0.048	-10000	0	-0.25	16	16
CDC25B	-0.019	0.16	-10000	0	-0.8	21	21
SGOL1	0.011	0.007	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.017	0.077	-10000	0	-0.39	21	21
CDC14B	0.009	0.034	-10000	0	-0.43	3	3
CDC20	-0.005	0.12	-10000	0	-0.81	12	12
PLK1/PBIP1	-0.004	0.032	-10000	0	-0.48	2	2
mitosis	0.001	0.006	0.04	12	-0.022	4	16
FBXO5	0.021	0.02	-10000	0	-10000	0	0
CDC2	0.001	0.004	-10000	0	-0.017	21	21
NDC80	-0.001	0.11	-10000	0	-0.81	9	9
metaphase plate congression	0.016	0.013	-10000	0	-10000	0	0
ERCC6L	-0.015	0.072	-10000	0	-0.37	21	21
NLP/gamma Tubulin	0.014	0.012	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.015	0.011	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-0.011	4	4
PPP1R12A	0.013	0.001	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-0.011	4	4
PLK1/PRC1-2	0.03	0.018	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.01	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.016	0.048	-10000	0	-0.46	4	4
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.033	-10000	0	-0.38	1	1
microtubule-based process	0.023	0.019	-10000	0	-10000	0	0
Golgi organization	0.017	0.022	-10000	0	-0.16	1	1
Cohesin/SA2	-0.002	0.013	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0.001	-10000	0	-10000	0	0
KIF20A	0.014	0	-10000	0	-10000	0	0
APC/C/CDC20	0.011	0.083	-10000	0	-0.52	12	12
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.004	0.032	-10000	0	-0.48	2	2
PRC1	0.014	0	-10000	0	-10000	0	0
ECT2	0.019	0.053	-10000	0	-0.48	5	5
C13orf34	0.017	0.046	-10000	0	-0.47	4	4
NUDC	0.016	0.013	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.021	0.025	-10000	0	-10000	0	0
spindle assembly	0.017	0.017	-10000	0	-10000	0	0
spindle stabilization	0.015	0.014	-10000	0	-0.17	1	1
APC/C/HCDH1	0.016	0.029	-10000	0	-0.36	3	3
MKLP2/PLK1	0.023	0.019	-10000	0	-10000	0	0
CCNB1	0.014	0.003	-10000	0	-10000	0	0
PPP1CB	0.013	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	0.016	0.06	-10000	0	-0.42	9	9
TUBG1	0.015	0.011	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.016	0.076	-10000	0	-0.38	21	21
MLF1IP	0.01	0.04	-10000	0	-0.64	2	2
INCENP	0.013	0.001	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.035	0.08	-10000	0	-0.41	5	5
BAG4	0.011	0.037	-10000	0	-0.58	2	2
BAD	0.029	0.029	-10000	0	-10000	0	0
NFKBIA	0.012	0.036	-10000	0	-0.81	1	1
BIRC3	-0.023	0.17	-10000	0	-0.81	23	23
BAX	0.029	0.029	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.022	-10000	0	-0.094	9	9
IKBKB	0.041	0.076	-10000	0	-10000	0	0
MAP2K2	0.041	0.031	-10000	0	-10000	0	0
MAP2K1	0.041	0.031	-10000	0	-10000	0	0
SMPD1	0.018	0.022	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.009	0.16	-10000	0	-0.61	7	7
MAP2K4	0.035	0.029	-10000	0	-10000	0	0
protein ubiquitination	0.043	0.077	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.046	0.034	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.036	0.031	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.021	0.031	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.001	0.024	-10000	0	-0.54	1	1
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.029	0.03	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.044	0.031	-10000	0	-10000	0	0
MAPK1	0.044	0.031	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	-0.001	0.027	-10000	0	-0.62	1	1
FADD	-0.019	0.17	-10000	0	-0.43	65	65
KSR1	0.029	0.031	-10000	0	-10000	0	0
MAPK8	0.038	0.044	-10000	0	-10000	0	0
TRAF2	0.004	0.088	-10000	0	-0.81	6	6
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.041	0.076	-10000	0	-10000	0	0
TNF R/SODD	-0.001	0.026	-10000	0	-0.42	2	2
TNF	-0.024	0.17	-10000	0	-0.77	25	25
CYCS	0.031	0.03	0.14	4	-10000	0	4
IKBKG	0.041	0.076	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.083	-10000	0	-0.42	9	9
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.031	0.03	0.14	4	-10000	0	4
TNF/TNF R/SODD	-0.025	0.11	-10000	0	-0.53	21	21
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.022	-10000	0	-10000	0	0
NSMAF	0.035	0.079	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.002	0.092	-10000	0	-0.68	9	9

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.014	0	-10000	0	-10000	0	0
NFATC1	0.06	0.018	-10000	0	-10000	0	0
NFATC2	0.024	0.063	-10000	0	-0.36	5	5
NFATC3	0.025	0.019	-10000	0	-0.4	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.011	0.076	-10000	0	-0.38	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.036	0.098	-10000	0	-0.56	7	7
BCL2/BAX	-0.009	0.067	-10000	0	-0.5	9	9
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.002	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.002	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.018	0.071	-10000	0	-0.37	2	2
Calcineurin A alpha-beta B1/BCL2	0.002	0.091	-10000	0	-0.68	9	9
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.018	0.071	0.37	2	-10000	0	2
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	0.008	0.062	-10000	0	-0.69	4	4
MAP3K8	0.01	0.045	-10000	0	-0.58	3	3
NFAT4/CK1 alpha	0	0.01	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.014	0.053	-10000	0	-10000	0	0
CABIN1	0.011	0.076	-10000	0	-0.38	4	4
CALM1	0.014	0.002	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.014	0	-10000	0	-10000	0	0
CAMK4	-0.025	0.17	-10000	0	-0.76	26	26
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.03	0.13	-10000	0	-0.62	25	25
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.006	0.068	-10000	0	-0.58	7	7
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.001	0.019	-10000	0	-10000	0	0
PRKCH	0.014	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.018	-10000	0	-0.41	1	1
CASP3	0.014	0.002	-10000	0	-10000	0	0
PIM1	0.012	0.026	-10000	0	-0.58	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.022	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.045	0.018	-10000	0	-10000	0	0
PRKCB	0.002	0.095	-10000	0	-0.75	8	8
PRKCE	0.012	0.026	-10000	0	-0.58	1	1
JNK2/NFAT4	0.03	0.017	-10000	0	-0.35	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.014	0	-10000	0	-10000	0	0
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.013	0.026	-10000	0	-0.58	1	1
PRKCA	0.011	0.044	-10000	0	-0.69	2	2
PRKCG	-0.083	0.26	-10000	0	-0.81	59	59
PRKCQ	0	0.092	-10000	0	-0.62	11	11
FKBP38/BCL2	-0.009	0.067	-10000	0	-0.5	9	9
EP300	0.013	0.026	-10000	0	-0.58	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.061	0.038	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.021	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.025	0.11	-10000	0	-0.5	26	26
NFATc/ERK1	0.065	0.017	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.036	0.098	-10000	0	-0.5	11	11
NR4A1	0.048	0.098	-10000	0	-0.55	10	10
GSK3B	0.014	0.002	-10000	0	-10000	0	0
positive T cell selection	0.025	0.019	-10000	0	-0.39	1	1
NFAT1/CK1 alpha	-0.012	0.037	-10000	0	-0.36	2	2
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.002	-10000	0	-10000	0	0
AKAP5	-0.026	0.18	-10000	0	-0.81	25	25
MEF2D	0.014	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.065	0.019	-10000	0	-10000	0	0
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.002	0.092	-10000	0	-0.68	9	9

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0	0.095	-9999	-0.64	11	11
HRAS	0.012	0.036	-9999	-0.81	1	1
EGFR	-0.015	0.15	-9999	-0.76	19	19
AKT	0.037	0.047	-9999	-0.41	1	1
FOXO3	0.014	0	-9999	-10000	0	0
AKT1	0.014	0	-9999	-10000	0	0
FOXO1	0.014	0	-9999	-10000	0	0
AKT3	-0.001	0.11	-9999	-0.81	9	9
FOXO4	0.011	0.037	-9999	-0.58	2	2
MET	0.005	0.08	-9999	-0.73	6	6
PIK3CA	0.014	0	-9999	-10000	0	0
PIK3CB	0.014	0	-9999	-10000	0	0
NRAS	0.014	0	-9999	-10000	0	0
PIK3CG	-0.021	0.16	-9999	-0.76	23	23
PIK3R3	0.012	0.026	-9999	-0.58	1	1
PIK3R2	0.014	0	-9999	-10000	0	0
NF1	0.014	0	-9999	-10000	0	0
RAS	0.016	0.047	-9999	-0.34	1	1
ERBB2	0.009	0.062	-9999	-0.81	3	3
proliferation/survival/translation	-0.031	0.027	-9999	-10000	0	0
PI3K	0.023	0.052	-9999	-0.26	3	3
PIK3R1	0.011	0.037	-9999	-0.58	2	2
KRAS	0.01	0.051	-9999	-0.81	2	2
FOXO	0.047	0.028	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.028	-9999	-10000	0	0
DAPP1	0.015	0.088	-9999	-0.37	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.002	0.16	-9999	-0.64	15	15
mol:DAG	0.029	0.085	-9999	-0.3	9	9
HRAS	0.013	0.036	-9999	-0.8	1	1
RAP1A	0.014	0.002	-9999	-10000	0	0
ARF5/GDP	0.04	0.041	-9999	-10000	0	0
PLCG2	0.012	0.026	-9999	-0.58	1	1
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.002	0.03	-9999	-10000	0	0
ARF1/GTP	-0.002	0.027	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.03	-9999	-10000	0	0
ADAP1	-0.003	0.03	-9999	-10000	0	0
ARAP3	-0.002	0.03	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.014	0	-9999	-10000	0	0
ARHGEF6	0.007	0.063	-9999	-0.58	6	6
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.014	0.002	-9999	-10000	0	0
FYN	0.012	0.036	-9999	-0.81	1	1
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.012	0.036	-9999	-0.81	1	1
mol:Ca2+	0.027	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.007	0.063	-9999	-0.58	6	6
ZAP70	-0.024	0.17	-9999	-0.77	25	25
mol:IP3	0.031	0.062	-9999	-10000	0	0
LYN	0.012	0.036	-9999	-0.81	1	1
ARF1/GDP	0.04	0.041	-9999	-10000	0	0
RhoA/GDP	-0.003	0.028	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.015	-9999	-10000	0	0
BLNK	-0.043	0.17	-9999	-0.58	50	50
actin cytoskeleton reorganization	0.062	0.043	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.03	0.023	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0	0.004	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.028	-9999	-10000	0	0
RhoA/GTP	-0.002	0.028	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.016	0.17	-9999	-0.7	16	16
BLK	-0.1	0.28	-9999	-0.77	75	75
PDPK1	0.012	0.026	-9999	-0.58	1	1
CYTH1	-0.002	0.028	-9999	-10000	0	0
HCK	0.006	0.076	-9999	-0.76	5	5
CYTH3	-0.002	0.028	-9999	-10000	0	0
CYTH2	-0.002	0.028	-9999	-10000	0	0
KRAS	0.011	0.051	-9999	-0.8	2	2
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.003	0.031	-9999	-0.44	2	2
SGK1	-0.003	0.034	-9999	-0.48	2	2
INPP5D	0.011	0.037	-9999	-0.58	2	2
mol:GDP	0.033	0.043	-9999	-0.32	1	1
SOS1	0.014	0	-9999	-10000	0	0
SYK	0.01	0.045	-9999	-0.58	3	3
ARF6/GDP	-0.003	0.028	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.03	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.03	-9999	-10000	0	0
VAV1	0.003	0.081	-9999	-0.6	9	9
mol:PI-3-4-P2	0.023	0.027	-9999	-0.42	2	2
RAS family/GTP/PI3K Class I	0.031	0.033	-9999	-10000	0	0
PLEKHA1	0.03	0.023	-9999	-10000	0	0
Rac1/GDP	0.04	0.041	-9999	-10000	0	0
LAT	-0.009	0.13	-9999	-0.81	14	14
Rac1/GTP	0.034	0.056	-9999	-0.35	1	1
ITK	-0.013	0.068	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.029	0.11	-9999	-0.45	9	9
LCK	-0.005	0.12	-9999	-0.81	12	12
BTK	-0.004	0.038	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.049	0.037	-10000	0	-0.37	2	2
adherens junction organization	0.037	0.058	-10000	0	-0.54	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.04	0.084	-10000	0	-0.6	1	1
FMN1	0.022	0.093	-10000	0	-0.65	3	3
mol:IP3	0.041	0.036	-10000	0	-0.39	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.035	0.05	-10000	0	-0.61	2	2
CTNNB1	0.012	0.026	-10000	0	-0.58	1	1
AKT1	0.047	0.039	-10000	0	-0.42	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.039	0.061	-10000	0	-0.47	7	7
CTNND1	0.015	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.042	0.046	-10000	0	-0.56	2	2
VASP	0.042	0.047	-10000	0	-0.58	2	2
ZYX	0.042	0.047	-10000	0	-0.58	2	2
JUB	0.041	0.049	-10000	0	-0.58	2	2
EGFR(dimer)	0.025	0.097	-10000	0	-0.46	17	17
E-cadherin/beta catenin-gamma catenin	-0.005	0.051	-10000	0	-0.64	2	2
mol:PI-3-4-5-P3	-0.004	0.035	-10000	0	-0.45	2	2
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
PI3K	-0.004	0.036	-10000	0	-0.46	2	2
FYN	0.046	0.059	-10000	0	-0.57	1	1
mol:Ca2+	0.04	0.035	-10000	0	-0.38	2	2
JUP	0.011	0.036	-10000	0	-0.57	2	2
PIK3R1	0.012	0.037	-10000	0	-0.58	2	2
mol:DAG	0.041	0.036	-10000	0	-0.39	2	2
CDH1	0.006	0.063	-10000	0	-0.57	6	6
RhoA/GDP	0.04	0.084	-10000	0	-0.6	1	1
establishment of polarity of embryonic epithelium	0.042	0.046	-10000	0	-0.56	2	2
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.015	0.15	-10000	0	-0.76	19	19
CASR	0.038	0.065	-10000	0	-0.4	8	8
RhoA/GTP	-0.003	0.027	-10000	0	-10000	0	0
AKT2	0.047	0.039	-10000	0	-0.42	2	2
actin cable formation	0.029	0.09	-10000	0	-0.62	3	3
apoptosis	0.004	0.033	0.41	2	-10000	0	2
CTNNA1	0.015	0.001	-10000	0	-10000	0	0
mol:GDP	0.034	0.089	-10000	0	-0.42	16	16
PIP5K1A	0.042	0.047	-10000	0	-0.58	2	2
PLCG1	-0.004	0.031	-10000	0	-0.4	2	2
Rac1/GTP	-0.017	0.079	-10000	0	-0.41	17	17
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.006	0.053	-9999	-0.67	2	2
E-cadherin/beta catenin	-0.006	0.048	-9999	-0.42	7	7
CTNNB1	0.012	0.026	-9999	-0.58	1	1
JUP	0.011	0.037	-9999	-0.58	2	2
CDH1	0.007	0.063	-9999	-0.58	6	6

×

Canonical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.085	0.033	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
RIP2/NOD2	-0.005	0.049	-9999	-0.5	5	5
NFKBIA	0.048	0.035	-9999	-0.75	1	1
BIRC2	-0.005	0.12	-9999	-0.81	12	12
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.006	0.033	-9999	-10000	0	0
IKK complex/A20	-0.022	0.085	-9999	-0.57	2	2
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.046	0.042	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.025	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.007	0.068	-9999	-0.67	5	5
NFKB1	0.017	0.005	-9999	-10000	0	0
RELA	0.017	0.005	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	-0.014	0.093	-9999	-0.62	12	12
ATM	0.012	0.026	-9999	-0.58	1	1
TNF/TNFR1A	-0.028	0.13	-9999	-0.58	25	25
TRAF6	0.014	0	-9999	-10000	0	0
PRKCA	0.011	0.044	-9999	-0.69	2	2
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.024	0.17	-9999	-0.77	25	25
NF kappa B1 p50/RelA	-0.001	0.014	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.034	-9999	-0.74	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0.005	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
IKK complex	0.053	0.039	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.035	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0	0	-9999	-10000	0	0
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.001	0.027	-9999	-0.62	1	1
GATA1/HDAC5	-0.001	0.027	-9999	-0.62	1	1
GATA2/HDAC5	-0.003	0.042	-9999	-0.55	3	3
HDAC5/BCL6/BCoR	-0.001	0.015	-9999	-10000	0	0
HDAC9	-0.021	0.16	-9999	-0.81	22	22
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.009	0.057	-9999	-0.73	3	3
HDAC4/RFXANK	-0.001	0.027	-9999	-0.62	1	1
BCOR	0.012	0.026	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	0.033	0.049	-9999	-10000	0	0
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.014	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.027	-9999	-0.62	1	1
CAMK4	-0.025	0.17	-9999	-0.76	26	26
Tubulin/HDAC6	0	0	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
GATA1	0.009	0.036	-9999	-0.81	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.032	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	0	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.018	-9999	-0.42	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.025	0.11	-9999	-0.53	21	21
HDAC4/ER alpha	-0.027	0.12	-9999	-0.51	28	28
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.032	0.049	-9999	-10000	0	0
cell motility	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.024	0.16	-9999	-0.68	28	28
HDAC6/HDAC11	-0.001	0.018	-9999	-0.42	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.001	0.1	-9999	-0.68	11	11
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.008	0.053	-9999	-0.45	5	5
GNG2	0.014	0	-9999	-10000	0	0
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.014	0	-9999	-10000	0	0
HDAC11	0.012	0.026	-9999	-0.58	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.014	0	-9999	-10000	0	0
RFXANK	0.012	0.036	-9999	-0.81	1	1
nuclear import	-0.031	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.01	0.044	0.42	1	-10000	0	1
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.008	0.062	-10000	0	-0.49	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.008	0.067	-10000	0	-0.75	4	4
RhoA/GTP	-0.01	0.045	-10000	0	-0.43	1	1
negative regulation of cAMP metabolic process	0.024	0.059	-10000	0	-0.47	1	1
GNAZ	-0.014	0.14	-10000	0	-0.74	19	19
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.007	0.072	-10000	0	-0.81	4	4
S1PR5	0.008	0.062	-10000	0	-0.69	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.024	0.059	-10000	0	-0.48	1	1
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.026	-10000	0	-0.58	1	1

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.029	0.085	-9999	-0.43	17	17
KLHL20	-0.011	0.039	-9999	-0.3	2	2
CYFIP2	0.011	0.044	-9999	-0.69	2	2
Rac1/GDP	0.058	0.041	-9999	-10000	0	0
ENAH	0.037	0.063	-9999	-0.49	7	7
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.012	0.036	-9999	-0.81	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.012	0.026	-9999	-0.58	1	1
CDC42/GTP	-0.003	0.025	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.028	-9999	-0.22	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.04	-9999	-10000	0	0
RAPGEF1	0.051	0.051	-9999	-0.4	1	1
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.007	0.054	-9999	-0.47	7	7
CRK	0.045	0.054	-9999	-0.42	7	7
E-cadherin/gamma catenin/alpha catenin	-0.005	0.051	-9999	-0.67	2	2
alphaE/beta7 Integrin	-0.002	0.026	-9999	-0.42	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
NCKAP1	0.012	0.036	-9999	-0.81	1	1
Rap1/GTP/I-afadin	-0.001	0.022	-9999	-0.49	1	1
DLG1	0.037	0.058	-9999	-0.45	7	7
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.019	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.005	0.04	-9999	-0.49	1	1
PI3K	-0.003	0.024	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.006	0.06	-9999	-0.53	6	6
TIAM1	0.007	0.063	-9999	-0.58	6	6
E-cadherin(dimer)/Ca2+	-0.004	0.033	-9999	-10000	0	0
AKT1	-0.002	0.014	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
CDH1	0.007	0.063	-9999	-0.58	6	6
RhoA/GDP	0.058	0.04	-9999	-10000	0	0
actin cytoskeleton organization	-0.008	0.029	-9999	-0.21	2	2
CDC42/GDP	0.058	0.04	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.022	0.042	-9999	-0.34	6	6
ITGB7	0.011	0.037	-9999	-0.58	2	2
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.004	0.035	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.004	0.034	-9999	-0.3	7	7
mol:GDP	0.055	0.045	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.037	-9999	-0.58	2	2
p120 catenin/RhoA/GDP	-0.004	0.03	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.028	0.049	-9999	-0.25	13	13
NME1	0.012	0.036	-9999	-0.81	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.037	0.058	-9999	-0.45	7	7
regulation of cell-cell adhesion	-0.003	0.022	-9999	-10000	0	0
WASF2	-0.004	0.014	-9999	-10000	0	0
Rap1/GTP	-0.004	0.029	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.047	-9999	-0.58	2	2
CCND1	0.032	0.06	-9999	-0.32	13	13
VAV2	0.039	0.077	-9999	-0.46	1	1
RAP1/GDP	-0.001	0.031	-9999	-10000	0	0
adherens junction assembly	0.038	0.056	-9999	-0.44	7	7
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
PIP5K1C	0.014	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.006	0.045	-9999	-0.56	2	2
E-cadherin/beta catenin	-0.004	0.041	-9999	-0.38	6	6
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.038	0.058	-9999	-0.45	7	7
PIK3CA	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.017	0.062	-9999	-0.47	3	3
E-cadherin/beta catenin/alpha catenin	-0.005	0.04	-9999	-0.34	7	7
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.056	-9999	-0.48	7	7

×

Alternative 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.005	0.048	-9999	-0.45	6	6
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.007	0.066	-9999	-0.62	6	6
RELB	0.004	0.088	-9999	-0.81	6	6
NFKB2	0.014	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.006	0.058	-9999	-0.54	6	6
regulation of B cell activation	-0.006	0.058	-9999	-0.54	6	6

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.012	0.026	-9999	-0.58	1	1
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	0.011	-9999	-10000	0	0
SMAD3/SMAD4	0.049	0.012	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.015	-9999	-0.34	1	1
SMAD2/SMAD2/SMAD4	0	0.011	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
SMAD2/SMAD4	0.021	0.014	-9999	-0.31	1	1
MAP3K1	0.014	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.015	0.078	-9999	-0.42	19	19
MAPK3	0.014	0	-9999	-10000	0	0
MAPK1	0.014	0	-9999	-10000	0	0
NUP214	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
CTDSP2	0.014	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	-0.007	0.11	-9999	-0.58	18	18
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.014	0	-9999	-10000	0	0
PIAS4	0.014	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.011	0.037	-9999	-0.58	2	2
PLK4	0.014	0	-9999	-10000	0	0
regulation of centriole replication	0.023	0.027	-9999	-0.42	2	2

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.078	0.087	-10000	0	-0.39	1	1
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.057	0.13	0.3	6	-0.43	1	7
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.014	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.024	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
ASIP	-0.006	0.11	-10000	0	-0.81	10	10
PRKCI	0.014	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.026	-10000	0	-0.58	1	1
TRIP10	0.014	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.048	0.02	-10000	0	-10000	0	0
VAMP2	0.014	0	-10000	0	-10000	0	0
SLC2A4	-0.063	0.14	0.3	6	-0.48	1	7
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.027	0	-10000	0	-10000	0	0
SFN	0.008	0.062	-10000	0	-0.69	4	4
LNPEP	0.011	0.037	-10000	0	-0.58	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.019	0.084	-9999	-0.4	21	21
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.075	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
ZFPM1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.014	0	-9999	-10000	0	0
Histones	-0.008	0.036	-9999	-10000	0	0
YY1/LSF	0.019	0.063	-9999	-0.6	1	1
SMG5	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.02	0.073	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.022	0.054	-9999	-0.34	1	1
SAP18	0.014	0	-9999	-10000	0	0
RELA	0.027	0.062	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
HDAC3/TR2	0.023	0.052	-9999	-10000	0	0
NuRD/MBD3 Complex	0.05	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.057	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.009	0.057	-9999	-0.73	3	3
GATA1	0.009	0.036	-9999	-0.81	1	1
Mad/Max	-0.004	0.04	-9999	-0.42	5	5
NuRD/MBD3 Complex/GATA1/Fog1	0.061	0.013	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.012	0.026	-9999	-0.58	1	1
MAX	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
NFKBIA	0.017	0.06	-9999	-0.38	1	1
KAT2B	-0.016	0.13	-9999	-0.58	26	26
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.045	0.015	-9999	-10000	0	0
SIN3 complex	-0.001	0.021	-9999	-0.48	1	1
SMURF1	0.014	0	-9999	-10000	0	0
CHD3	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.036	-9999	-0.81	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.014	0	-9999	-10000	0	0
YY1/HDAC3	0.024	0.071	-9999	-0.52	1	1
YY1/HDAC2	0.019	0.063	-9999	-0.6	1	1
YY1/HDAC1	0.019	0.063	-9999	-0.6	1	1
NuRD/MBD2 Complex (MeCP1)	0.05	0.009	-9999	-10000	0	0
PPARG	-0.13	0.16	-9999	-0.46	21	21
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.023	0.052	-9999	-10000	0	0
MBD3L2	-0.002	0.05	-9999	-0.81	2	2
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.016	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC3	0.018	0.057	-9999	-10000	0	0
HDAC2	0.014	0	-9999	-10000	0	0
YY1	0.016	0.074	-9999	-0.68	1	1
HDAC8	0.014	0	-9999	-10000	0	0
SMAD7	0.014	0	-9999	-10000	0	0
NCOR2	0.014	0	-9999	-10000	0	0
MXD1	0.008	0.058	-9999	-0.58	5	5
STAT3	0.027	0.016	-9999	-0.34	1	1
NFKB1	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.011	0.05	-9999	-0.56	1	1
YY1/SAP30/HDAC1	-0.012	0.057	-9999	-0.62	2	2
EP300	0.012	0.026	-9999	-0.58	1	1
STAT3 (dimer non-phopshorylated)	0.027	0.016	-9999	-0.34	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.06	-9999	-0.38	1	1
histone deacetylation	0.05	0.009	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.033	0.049	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GATAD2B	0.014	0	-9999	-10000	0	0
GATAD2A	0.014	0	-9999	-10000	0	0
GATA2/HDAC3	0.02	0.065	-9999	-0.59	2	2
GATA1/HDAC1	-0.001	0.027	-9999	-0.62	1	1
GATA1/HDAC3	0.016	0.057	-9999	-0.48	1	1
CHD4	0.014	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.028	0.13	-9999	-0.58	25	25
SIN3/HDAC complex/Mad/Max	0.048	0.024	-9999	-10000	0	0
NuRD Complex	0.059	0.01	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.008	0.036	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
MTA2	0.014	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC1	0.032	0	-9999	-10000	0	0
HDAC complex	-0.001	0.013	-9999	-10000	0	0
GATA1/Fog1	-0.001	0.027	-9999	-0.62	1	1
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.024	0.17	-9999	-0.77	25	25
negative regulation of cell growth	0.048	0.024	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.05	0.009	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.016	0.068	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.048	0.014	-9999	-10000	0	0
TFCP2	0.014	0	-9999	-10000	0	0
NR2C1	0.014	0	-9999	-10000	0	0
MBD3	0.014	0	-9999	-10000	0	0
MBD2	0.014	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.039	0.043	-9999	-0.61	2	2
PLK1	0.11	0.11	-9999	-0.91	2	2
CDKN1B	0.15	0.051	-9999	-10000	0	0
FOXO3	0.11	0.11	-9999	-0.89	1	1
KAT2B	-0.003	0.13	-9999	-0.57	26	26
FOXO1/SIRT1	0.008	0.032	-9999	-10000	0	0
CAT	0.11	0.11	-9999	-0.98	2	2
CTNNB1	0.012	0.026	-9999	-0.58	1	1
AKT1	0.029	0.01	-9999	-10000	0	0
FOXO1	0.043	0.023	-9999	-10000	0	0
MAPK10	0.026	0.08	-9999	-0.45	4	4
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.1	0.05	-9999	-10000	0	0
response to oxidative stress	0.017	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	0.002	0.075	-9999	-0.7	2	2
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.014	0.026	-9999	-0.58	1	1
BCL2L11	0.042	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.043	0.03	-9999	-0.46	1	1
mol:GDP	0.017	0.011	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
GADD45A	0.12	0.053	-9999	-0.48	1	1
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.08	0.016	-9999	-10000	0	0
MST1	0.018	0.081	-9999	-0.72	6	6
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.062	0.025	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.041	0.038	-9999	-10000	0	0
MAPK9	0.045	0.005	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.005	0.031	-9999	-0.57	1	1
SOD2	0.16	0.06	-9999	-10000	0	0
RBL2	0.12	0.077	-9999	-10000	0	0
RAL/GDP	0.035	0.011	-9999	-10000	0	0
CHUK	0.026	0.009	-9999	-10000	0	0
Ran/GTP	0.015	0.001	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
RAL/GTP	0.044	0.008	-9999	-10000	0	0
CSNK1G1	0.014	0	-9999	-10000	0	0
FASLG	-0.025	0.27	-9999	-0.92	39	39
SKP2	0.012	0.036	-9999	-0.81	1	1
USP7	0.015	0	-9999	-10000	0	0
IKBKB	0.026	0.009	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.79	1	1
FOXO1-3a-4/beta catenin	0.12	0.098	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.043	0.03	-9999	-0.46	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.024	0.038	-9999	-0.56	2	2
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.001	-9999	-10000	0	0
ZFAND5	0.1	0.045	-9999	-10000	0	0
SFN	0.008	0.062	-9999	-0.69	4	4
CDK2	0.014	0.004	-9999	-10000	0	0
FOXO3A/14-3-3	0.076	0.034	-9999	-10000	0	0
CREBBP	0.014	0.004	-9999	-10000	0	0
FBXO32	0.11	0.14	-9999	-1.3	3	3
BCL6	0.12	0.077	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.001	0.018	-9999	-0.42	1	1
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.022	0.049	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.04	-9999	-0.45	1	1
NFKBIA	0.024	0.045	-9999	-0.52	1	1
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.028	0	-9999	-10000	0	0
ARRB2	0.018	0	-9999	-10000	0	0
REL	0.003	0.077	-9999	-0.58	9	9
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.016	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.021	0	-9999	-10000	0	0
PIK3R1	0.011	0.037	-9999	-0.58	2	2
NFKB1	0.024	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.032	0.041	-9999	-0.41	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.048	0.039	-9999	-0.43	1	1
SRC	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.026	-9999	-0.42	2	2
NF kappa B1 p50/RelA	0.032	0.041	-9999	-0.42	1	1
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	0.01	0.045	-9999	-0.58	3	3
I kappa B alpha/PIK3R1	0.029	0.047	-9999	-0.49	1	1
cell death	0.046	0.038	-9999	-0.41	1	1
NF kappa B1 p105/c-Rel	0.022	0.049	-9999	-10000	0	0
LCK	-0.005	0.12	-9999	-0.81	12	12
BCL3	0.012	0.026	-9999	-0.58	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.014	0	-10000	0	-10000	0	0
mol:PIP3	-0.003	0.028	-10000	0	-10000	0	0
FRAP1	0.015	0.009	-10000	0	-10000	0	0
AKT1	0.028	0.028	-10000	0	-10000	0	0
INSR	0.012	0.026	-10000	0	-0.58	1	1
Insulin Receptor/Insulin	-0.003	0.037	-10000	0	-0.48	3	3
mol:GTP	-0.002	0.019	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.006	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.002	0.017	-10000	0	-10000	0	0
TSC1	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.015	0.031	-10000	0	-0.34	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.017	-10000	0	-10000	0	0
MAP3K5	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.011	0.037	-10000	0	-0.58	2	2
apoptosis	0.011	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	3	3
EIF4B	0.034	0.016	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.003	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.032	-10000	0	-0.3	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.033	0.013	-10000	0	-10000	0	0
FKBP1A	0.014	0	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.016	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	3	3
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.003	0.028	-10000	0	-10000	0	0
EIF4E	0.014	0	-10000	0	-10000	0	0
ASK1/PP5C	0.023	0.006	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.002	0.02	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	3	-10000	0	3
RPS6	0.014	0	-10000	0	-10000	0	0
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.007	0.029	-10000	0	-0.38	3	3
INS	-0.003	0.05	-10000	0	-0.81	2	2
PTEN	0.013	0	-10000	0	-10000	0	0
PDK2	-0.002	0.025	-10000	0	-10000	0	0
EIF4EBP1	0.006	0.051	-10000	0	-0.38	9	9
PIK3CA	0.014	0	-10000	0	-10000	0	0
PPP2R5D	0.022	0.008	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.035	-10000	0	-0.49	2	2
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.016	0.035	-10000	0	-0.49	2	2
eIF4E/4E-BP1	0.014	0.045	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.04	0.006	-9999	-10000	0	0
CDKN1A	0.04	0.006	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.014	0	-9999	-10000	0	0
FOXO3	0.04	0.006	-9999	-10000	0	0
AKT1	0	0.005	-9999	-10000	0	0
BAD	0.014	0	-9999	-10000	0	0
AKT3	0.011	0.052	-9999	-0.36	10	10
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.038	0.02	-9999	-10000	0	0
AKT1/ASK1	0	0.004	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.014	0	-9999	-10000	0	0
RAF1	0.014	0	-9999	-10000	0	0
JNK cascade	0	0.004	-9999	-10000	0	0
TSC1	0.04	0.006	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
AKT1/RAF1	0.039	0.006	-9999	-10000	0	0
EP300	0.012	0.026	-9999	-0.58	1	1
mol:GDP	0.033	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.04	0.006	-9999	-10000	0	0
YWHAQ	0.014	0	-9999	-10000	0	0
TBC1D4	0.025	0.014	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAPKAP1	0.014	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.046	0.013	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0
AKT1S1	0.04	0.006	-9999	-10000	0	0
CASP9	0.04	0.006	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.046	0.006	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.015	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0.01	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.002	-9999	-10000	0	0
CHUK	0.04	0.006	-9999	-10000	0	0
BAD/BCL-XL	0.053	0.006	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.018	0.016	-9999	-0.35	1	1
FOXO1-3a-4/14-3-3 family	0.062	0.017	-9999	-10000	0	0
PDPK1	0.012	0.026	-9999	-0.58	1	1
MDM2	0.04	0.006	-9999	-10000	0	0
MAPKKK cascade	-0.039	0.006	-9999	-10000	0	0
MDM2/Cbp/p300	0.051	0.014	-9999	-10000	0	0
TSC1/TSC2	0.046	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.01	-9999	-10000	0	0
glucose import	-0.12	0.17	-9999	-0.48	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.12	0.17	-9999	-0.48	1	1
GSK3A	0.04	0.006	-9999	-10000	0	0
FOXO1	0.04	0.006	-9999	-10000	0	0
GSK3B	0.04	0.006	-9999	-10000	0	0
SFN	0.008	0.062	-9999	-0.69	4	4
G1/S transition of mitotic cell cycle	0.046	0.006	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.05	0.019	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
KPNA1	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
RHEB	0.014	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.014	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.032	-9999	-9999
HDAC4	0.014	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.014	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.03	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.014	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.014	-9999	-9999
SUMO1/HDAC4	0.032	-9999	-9999
SUMO1/HDAC1	0.032	-9999	-9999
RANGAP1	0.014	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	-9999	-9999
Ran/GTP	0.028	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.014	-9999	-9999
UBE2I	0.014	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.014	-9999	-9999
PIAS1	0.014	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.008	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.022	0	-9999	-10000	0	0
AP2	-0.002	0.038	-9999	-0.62	2	2
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0.013	-9999	-0.26	1	1
CD4	0.011	0.044	-9999	-0.69	2	2
CLTA	0.012	0.036	-9999	-0.81	1	1
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0.01	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.01	0.051	-9999	-0.81	2	2
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.018	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.027	0.011	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.029	0.01	-9999	-10000	0	0
ARF1/GDP/Membrin	0.019	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.036	0.022	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.004	0.043	-9999	-0.49	4	4

pid_entity	TCGA.WA.A7H4	TCGA.WA.A7GZ	TCGA.UP.A6WW	TCGA.UF.A7JV
109_MAP3K5	0.058	0.058	0.058	0.058
47_PPARGC1A	0.014	0.014	0.014	-0.58
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	0.014	0.014	-0.81
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.017	0.013
84_STAT5B	0.039	0.038	-0.026	-0.022
84_STAT5A	0.039	0.038	-0.026	-0.022