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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	121
Syndecan-1-mediated signaling events	113
Syndecan-4-mediated signaling events	94
IL4-mediated signaling events	89
HIF-1-alpha transcription factor network	76
Osteopontin-mediated events	65
amb2 Integrin signaling	49
Glypican 2 network	43
IL23-mediated signaling events	43
Syndecan-2-mediated signaling events	42

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	0.3993	121	968	8	-0.31	0.14	1000	-1000	-0.026	-1000
Syndecan-1-mediated signaling events	0.3729	113	3844	34	-0.72	0.013	1000	-1000	-0.082	-1000
Syndecan-4-mediated signaling events	0.3102	94	6303	67	-0.74	0.099	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.2937	89	8099	91	-1.4	1.3	1000	-1000	-0.2	-1000
HIF-1-alpha transcription factor network	0.2508	76	5831	76	-1	0.022	1000	-1000	-0.2	-1000
Osteopontin-mediated events	0.2145	65	2499	38	-0.45	0.013	1000	-1000	-0.12	-1000
amb2 Integrin signaling	0.1617	49	4060	82	-0.61	0.013	1000	-1000	-0.11	-1000
Glypican 2 network	0.1419	43	173	4	-0.12	-0.12	1000	-1000	-0.048	-1000
IL23-mediated signaling events	0.1419	43	2592	60	-0.7	0.013	1000	-1000	-0.2	-1000
Syndecan-2-mediated signaling events	0.1386	42	2948	69	-0.44	0.027	1000	-1000	-0.076	-1000
Endothelins	0.1287	39	3749	96	-0.55	0.014	1000	-1000	-0.11	-1000
TCGA08_p53	0.1188	36	257	7	-0.24	0.12	1000	-1000	-0.019	-1000
Visual signal transduction: Cones	0.0957	29	1107	38	-0.31	0.013	1000	-1000	-0.075	-1000
p75(NTR)-mediated signaling	0.0957	29	3668	125	-0.55	0.013	1000	-1000	-0.13	-1000
Visual signal transduction: Rods	0.0858	26	1377	52	-0.46	0.013	1000	-1000	-0.11	-1000
FOXA2 and FOXA3 transcription factor networks	0.0792	24	1118	46	-0.54	0.021	1000	-1000	-0.12	-1000
Effects of Botulinum toxin	0.0792	24	636	26	-0.23	0.013	1000	-1000	-0.082	-1000
BMP receptor signaling	0.0726	22	1792	81	-0.41	0.047	1000	-1000	-0.12	-1000
Glypican 1 network	0.0726	22	1091	48	-0.4	0.035	1000	-1000	-0.058	-1000
PDGFR-beta signaling pathway	0.0726	22	2206	97	-0.21	0.014	1000	-1000	-0.1	-1000
Signaling events mediated by the Hedgehog family	0.0693	21	1109	52	-0.43	0.071	1000	-1000	-0.1	-1000
Ephrin B reverse signaling	0.0693	21	1032	48	-0.17	0.15	1000	-1000	-0.09	-1000
Calcium signaling in the CD4+ TCR pathway	0.0693	21	664	31	-0.48	0.014	1000	-1000	-0.11	-1000
Signaling events regulated by Ret tyrosine kinase	0.0660	20	1689	82	-0.18	0.013	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0660	20	1946	93	-0.33	0.17	1000	-1000	-0.11	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0660	20	1382	68	-0.52	0.025	1000	-1000	-0.16	-1000
IL12-mediated signaling events	0.0627	19	1690	87	-0.26	0.098	1000	-1000	-0.17	-1000
ErbB4 signaling events	0.0627	19	1364	69	-0.38	0.091	1000	-1000	-0.12	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0627	19	2374	120	-0.28	0.12	1000	-1000	-0.11	-1000
Coregulation of Androgen receptor activity	0.0594	18	1389	76	-0.52	0.042	1000	-1000	-0.067	-1000
Thromboxane A2 receptor signaling	0.0594	18	1979	105	-0.14	0.022	1000	-1000	-0.094	-1000
Nongenotropic Androgen signaling	0.0594	18	944	52	-0.11	0.044	1000	-1000	-0.075	-1000
BCR signaling pathway	0.0594	18	1820	99	-0.17	0.031	1000	-1000	-0.11	-1000
Caspase cascade in apoptosis	0.0561	17	1304	74	-0.14	0.049	1000	-1000	-0.066	-1000
LPA4-mediated signaling events	0.0528	16	196	12	-0.11	0.022	1000	-1000	-0.033	-1000
Glucocorticoid receptor regulatory network	0.0528	16	1879	114	-0.64	0.24	1000	-1000	-0.097	-1000
IL1-mediated signaling events	0.0528	16	992	62	-0.24	0.073	1000	-1000	-0.13	-1000
Canonical Wnt signaling pathway	0.0528	16	848	51	-0.34	0.12	1000	-1000	-0.082	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0528	16	1267	78	-0.11	0.035	1000	-1000	-0.11	-1000
Reelin signaling pathway	0.0495	15	874	56	-0.25	0.013	1000	-1000	-0.11	-1000
Integrins in angiogenesis	0.0495	15	1265	84	-0.45	0.019	1000	-1000	-0.12	-1000
Presenilin action in Notch and Wnt signaling	0.0462	14	865	61	-0.34	0.038	1000	-1000	-0.093	-1000
Signaling mediated by p38-gamma and p38-delta	0.0462	14	215	15	-0.14	0.024	1000	-1000	-0.052	-1000
EPHB forward signaling	0.0462	14	1232	85	-0.3	0.12	1000	-1000	-0.12	-1000
Regulation of nuclear SMAD2/3 signaling	0.0429	13	1895	136	-0.38	0.37	1000	-1000	-0.095	-1000
Signaling events mediated by PTP1B	0.0429	13	1019	76	-0.22	0.041	1000	-1000	-0.1	-1000
Syndecan-3-mediated signaling events	0.0429	13	459	35	-0.23	0.013	1000	-1000	-0.087	-1000
IL27-mediated signaling events	0.0429	13	667	51	-0.16	0.025	1000	-1000	-0.11	-1000
LPA receptor mediated events	0.0429	13	1382	102	-0.61	0.016	1000	-1000	-0.11	-1000
EGFR-dependent Endothelin signaling events	0.0429	13	286	21	-0.14	0.013	1000	-1000	-0.089	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0429	13	448	33	-0.31	0.037	1000	-1000	-0.087	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0396	12	436	34	-0.063	0.013	1000	-1000	-0.092	-1000
ErbB2/ErbB3 signaling events	0.0363	11	731	65	-0.38	0.026	1000	-1000	-0.093	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0363	11	626	54	-0.34	0.028	1000	-1000	-0.13	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0363	11	985	88	-0.44	0.077	1000	-1000	-0.14	-1000
Regulation of Androgen receptor activity	0.0363	11	801	70	-0.54	0.034	1000	-1000	-0.084	-1000
Ephrin A reverse signaling	0.0330	10	70	7	-0.02	0.003	1000	-1000	-0.041	-1000
Arf6 signaling events	0.0330	10	662	62	-0.16	0.044	1000	-1000	-0.084	-1000
PDGFR-alpha signaling pathway	0.0330	10	481	44	-0.17	0.03	1000	-1000	-0.075	-1000
Wnt signaling	0.0330	10	74	7	-0.074	0.013	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0330	10	1057	102	-0.18	0.046	1000	-1000	-0.13	-1000
Fc-epsilon receptor I signaling in mast cells	0.0297	9	876	97	-0.22	0.036	1000	-1000	-0.11	-1000
Cellular roles of Anthrax toxin	0.0264	8	338	39	-0.049	0.019	1000	-1000	-0.039	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0264	8	299	37	-0.078	0.013	1000	-1000	-0.099	-1000
Signaling events mediated by HDAC Class III	0.0264	8	348	40	-0.21	0.091	1000	-1000	-0.063	-1000
Signaling mediated by p38-alpha and p38-beta	0.0264	8	389	44	-0.17	0.013	1000	-1000	-0.066	-1000
Noncanonical Wnt signaling pathway	0.0231	7	182	26	-0.074	0.013	1000	-1000	-0.11	-1000
Nectin adhesion pathway	0.0231	7	461	63	-0.22	0.046	1000	-1000	-0.098	-1000
TRAIL signaling pathway	0.0231	7	378	48	-0.084	0.017	1000	-1000	-0.091	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0231	7	402	52	-0.24	0.03	1000	-1000	-0.085	-1000
S1P1 pathway	0.0231	7	277	36	-0.22	0.014	1000	-1000	-0.086	-1000
Retinoic acid receptors-mediated signaling	0.0231	7	417	58	-0.15	0.018	1000	-1000	-0.093	-1000
Plasma membrane estrogen receptor signaling	0.0231	7	673	86	-0.3	0.039	1000	-1000	-0.12	-1000
S1P3 pathway	0.0231	7	296	42	-0.22	0.041	1000	-1000	-0.081	-1000
Rapid glucocorticoid signaling	0.0231	7	141	20	-0.06	0.013	1000	-1000	-0.052	-1000
Signaling events mediated by PRL	0.0231	7	264	34	-0.14	0.032	1000	-1000	-0.066	-1000
Class IB PI3K non-lipid kinase events	0.0231	7	21	3	-0.004	-1000	1000	-1000	-0.009	-1000
JNK signaling in the CD4+ TCR pathway	0.0198	6	110	17	-0.042	0.036	1000	-1000	-0.089	-1000
a4b1 and a4b7 Integrin signaling	0.0198	6	34	5	-0.022	0.011	1000	-1000	-0.048	-1000
IFN-gamma pathway	0.0198	6	457	68	-0.18	0.041	1000	-1000	-0.12	-1000
FAS signaling pathway (CD95)	0.0198	6	284	47	-0.084	0.014	1000	-1000	-0.066	-1000
IL2 signaling events mediated by PI3K	0.0198	6	385	58	-0.16	0.056	1000	-1000	-0.11	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0198	6	461	74	-0.37	0.084	1000	-1000	-0.13	-1000
Ras signaling in the CD4+ TCR pathway	0.0198	6	115	17	-0.029	0.025	1000	-1000	-0.057	-1000
EPO signaling pathway	0.0165	5	318	55	-0.054	0.04	1000	-1000	-0.13	-1000
Ceramide signaling pathway	0.0165	5	407	76	-0.14	0.043	1000	-1000	-0.087	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0165	5	233	45	-0.084	0.041	1000	-1000	-0.12	-1000
IL6-mediated signaling events	0.0165	5	447	75	-0.1	0.067	1000	-1000	-0.12	-1000
FOXM1 transcription factor network	0.0165	5	266	51	-0.32	0.14	1000	-1000	-0.21	-1000
p38 MAPK signaling pathway	0.0165	5	252	44	-0.16	0.021	1000	-1000	-0.09	-1000
IL2 signaling events mediated by STAT5	0.0132	4	105	22	-0.056	0.045	1000	-1000	-0.069	-1000
IGF1 pathway	0.0132	4	242	57	-0.054	0.038	1000	-1000	-0.12	-1000
Insulin Pathway	0.0132	4	350	74	-0.29	0.042	1000	-1000	-0.1	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0099	3	110	28	-0.095	0.019	1000	-1000	-0.073	-1000
Circadian rhythm pathway	0.0099	3	84	22	-0.092	0.047	1000	-1000	-0.089	-1000
Arf6 downstream pathway	0.0099	3	146	43	-0.03	0.025	1000	-1000	-0.054	-1000
VEGFR1 specific signals	0.0099	3	189	56	-0.12	0.044	1000	-1000	-0.1	-1000
S1P4 pathway	0.0099	3	89	25	-0.035	0.029	1000	-1000	-0.076	-1000
Aurora B signaling	0.0099	3	247	67	-0.3	0.046	1000	-1000	-0.085	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0066	2	245	85	-0.092	0.066	1000	-1000	-0.093	-1000
Hedgehog signaling events mediated by Gli proteins	0.0066	2	141	65	-0.089	0.068	1000	-1000	-0.092	-1000
Aurora A signaling	0.0066	2	178	60	-0.075	0.033	1000	-1000	-0.084	-1000
ceramide signaling pathway	0.0066	2	99	49	-0.024	0.048	1000	-1000	-0.074	-1000
HIF-2-alpha transcription factor network	0.0066	2	112	43	-0.24	0.025	1000	-1000	-0.12	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0066	2	169	83	-0.069	0.067	1000	-1000	-0.11	-1000
Paxillin-dependent events mediated by a4b1	0.0066	2	95	36	-0.078	0.025	1000	-1000	-0.091	-1000
Regulation of p38-alpha and p38-beta	0.0066	2	161	54	-0.12	0.032	1000	-1000	-0.085	-1000
TCGA08_rtk_signaling	0.0066	2	55	26	-0.031	0.048	1000	-1000	-0.029	-1000
Class I PI3K signaling events	0.0066	2	187	73	-0.12	0.042	1000	-1000	-0.095	-1000
Arf6 trafficking events	0.0066	2	168	71	-0.27	0.047	1000	-1000	-0.099	-1000
Canonical NF-kappaB pathway	0.0033	1	43	39	-0.028	0.09	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class II	0.0033	1	111	75	-0.04	0.032	1000	-1000	-0.084	-1000
PLK1 signaling events	0.0033	1	148	85	-0.013	0.034	1000	-1000	-0.073	-1000
S1P5 pathway	0.0033	1	20	17	-0.007	0.029	1000	-1000	-0.076	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0033	1	223	125	-0.088	0.099	1000	-1000	-0.14	-1000
E-cadherin signaling in keratinocytes	0.0033	1	68	43	-0.016	0.052	1000	-1000	-0.085	-1000
E-cadherin signaling events	0.0033	1	8	5	-0.005	0.011	1000	-1000	-0.067	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	9	23	-0.006	0.05	1000	-1000	-0.09	-1000
BARD1 signaling events	0.0000	0	56	57	-0.007	0.074	1000	-1000	-0.086	-1000
PLK2 and PLK4 events	0.0000	0	0	3	0.013	0.025	1000	-1000	-0.022	-1000
Aurora C signaling	0.0000	0	6	7	-0.004	0.011	1000	-1000	-0.056	-1000
Insulin-mediated glucose transport	0.0000	0	27	32	-0.081	0.05	1000	-1000	-0.094	-1000
mTOR signaling pathway	0.0000	0	0	53	0	0.037	1000	-1000	-0.071	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	7	68	-0.14	0.064	1000	-1000	-0.09	-1000
Signaling events mediated by HDAC Class I	0.0000	0	58	104	-0.14	0.063	1000	-1000	-0.097	-1000
FoxO family signaling	0.0000	0	48	64	-0.016	0.16	1000	-1000	-0.1	-1000
Atypical NF-kappaB pathway	0.0000	0	18	31	-0.014	0.048	1000	-1000	-0.083	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	69	76	-0.016	0.06	1000	-1000	-0.11	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.031	1000	-1000	-0.079	-1000
Arf1 pathway	0.0000	0	7	54	-0.005	0.036	1000	-1000	-0.062	-1000
Alternative NF-kappaB pathway	0.0000	0	10	13	-0.004	0.013	1000	-1000	-0.086	-1000
Total	NA	1875	110355	7203	-29	-990	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	-0.1	0.24	-10000	0	-0.6	57	57
CDKN2C	0.009	0.15	-10000	0	-0.73	11	11
CDKN2A	-0.31	0.38	-10000	0	-0.77	124	124
CCND2	0.12	0.14	0.24	155	-0.15	1	156
RB1	-0.13	0.15	-10000	0	-0.26	154	154
CDK4	0.14	0.16	0.27	157	-10000	0	157
CDK6	0.14	0.16	0.27	154	-10000	0	154
G1/S progression	0.12	0.16	0.26	155	-10000	0	155

×

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	0.011	0.047	-9999	-0.8	1	1
CCL5	-0.097	0.28	-9999	-0.8	41	41
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.45	0.17	-9999	-0.54	221	221
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.42	0.17	-9999	-0.51	221	221
Syndecan-1/Syntenin	-0.42	0.17	-9999	-0.51	221	221
MAPK3	-0.38	0.16	-9999	-0.62	43	43
HGF/MET	-0.019	0.098	-9999	-0.52	11	11
TGFB1/TGF beta receptor Type II	0.011	0.047	-9999	-0.8	1	1
BSG	0.013	0	-9999	-10000	0	0
keratinocyte migration	-0.42	0.16	-9999	-0.5	221	221
Syndecan-1/RANTES	-0.48	0.23	-9999	-0.58	231	231
Syndecan-1/CD147	-0.4	0.16	-9999	-0.49	216	216
Syndecan-1/Syntenin/PIP2	-0.41	0.16	-9999	-0.5	221	221
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.4	0.15	-9999	-0.48	221	221
MMP7	-0.13	0.3	-9999	-0.76	55	55
HGF	-0.008	0.12	-9999	-0.7	9	9
Syndecan-1/CASK	-0.43	0.17	-9999	-0.52	221	221
Syndecan-1/HGF/MET	-0.42	0.17	-9999	-0.5	214	214
regulation of cell adhesion	-0.36	0.15	-9999	-0.59	43	43
HPSE	0.009	0.053	-9999	-0.64	2	2
positive regulation of cell migration	-0.45	0.17	-9999	-0.54	221	221
SDC1	-0.46	0.18	-9999	-0.55	221	221
Syndecan-1/Collagen	-0.45	0.17	-9999	-0.54	221	221
PPIB	0.013	0	-9999	-10000	0	0
MET	0.009	0.06	-9999	-0.72	2	2
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.61	0.35	-9999	-0.8	230	230
MAPK1	-0.38	0.16	-9999	-0.62	43	43
homophilic cell adhesion	-0.45	0.17	-9999	-0.54	221	221
MMP1	-0.72	0.25	-9999	-0.8	271	271

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.26	0.23	-9999	-0.46	170	170
Syndecan-4/Syndesmos	-0.42	0.25	-9999	-0.61	168	168
positive regulation of JNK cascade	-0.42	0.22	-9999	-0.57	184	184
Syndecan-4/ADAM12	-0.74	0.33	-9999	-0.94	211	211
CCL5	-0.097	0.28	-9999	-0.8	41	41
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	-0.27	0.39	-9999	-0.8	105	105
SDCBP	0.013	0	-9999	-10000	0	0
PLG	0.007	0.013	-9999	-10000	0	0
ADAM12	-0.63	0.33	-9999	-0.8	239	239
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.12	0.061	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.61	0.34	-9999	-0.8	202	202
Syndecan-4/CXCL12/CXCR4	-0.44	0.24	-9999	-0.61	184	184
Syndecan-4/Laminin alpha3	-0.53	0.33	-9999	-0.74	188	188
MDK	-0.01	0.14	-9999	-0.78	9	9
Syndecan-4/FZD7	-0.42	0.26	-9999	-0.62	168	168
Syndecan-4/Midkine	-0.43	0.26	-9999	-0.62	172	172
FZD7	0	0.1	-9999	-0.77	5	5
Syndecan-4/FGFR1/FGF	-0.4	0.23	-9999	-0.57	176	176
THBS1	-0.02	0.16	-9999	-0.77	13	13
integrin-mediated signaling pathway	-0.47	0.3	-9999	-0.68	177	177
positive regulation of MAPKKK cascade	-0.42	0.22	-9999	-0.57	184	184
Syndecan-4/TACI	-0.47	0.28	-9999	-0.66	185	185
CXCR4	-0.019	0.16	-9999	-0.8	12	12
cell adhesion	-0.22	0.2	-9999	-0.48	83	83
Syndecan-4/Dynamin	-0.42	0.25	-9999	-0.61	168	168
Syndecan-4/TSP1	-0.43	0.27	-9999	-0.64	168	168
Syndecan-4/GIPC	-0.42	0.25	-9999	-0.61	168	168
Syndecan-4/RANTES	-0.47	0.29	-9999	-0.67	183	183
ITGB1	0.011	0.047	-9999	-0.8	1	1
LAMA1	-0.37	0.41	-9999	-0.8	143	143
LAMA3	-0.22	0.37	-9999	-0.8	87	87
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.099	0.072	-9999	-0.77	1	1
Syndecan-4/alpha-Actinin	-0.42	0.25	-9999	-0.61	168	168
TFPI	0.009	0.06	-9999	-0.72	2	2
F2	-0.07	0.23	-9999	-0.81	26	26
alpha5/beta1 Integrin	-0.22	0.29	-9999	-0.61	106	106
positive regulation of cell adhesion	-0.68	0.36	-9999	-0.87	214	214
ACTN1	0.011	0.047	-9999	-0.8	1	1
TNC	-0.15	0.33	-9999	-0.8	61	61
Syndecan-4/CXCL12	-0.45	0.25	-9999	-0.62	181	181
FGF6	0.003	0.005	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.048	0.19	-9999	-0.65	28	28
TNFRSF13B	-0.093	0.27	-9999	-0.8	39	39
FGF2	-0.012	0.13	-9999	-0.68	11	11
FGFR1	0.008	0.066	-9999	-0.8	2	2
Syndecan-4/PI-4-5-P2	-0.42	0.25	-9999	-0.62	168	168
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.44	0.41	-9999	-0.8	170	170
cell migration	-0.041	0.02	-9999	-10000	0	0
PRKCD	0.026	0.012	-9999	-10000	0	0
vasculogenesis	-0.41	0.26	-9999	-0.61	168	168
SDC4	-0.45	0.27	-9999	-0.65	168	168
Syndecan-4/Tenascin C	-0.5	0.32	-9999	-0.72	177	177
Syndecan-4/PI-4-5-P2/PKC alpha	-0.097	0.048	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.42	0.25	-9999	-0.61	168	168
MMP9	-0.6	0.35	-9999	-0.8	230	230
Rac1/GTP	-0.23	0.21	-9999	-0.49	83	83
cytoskeleton organization	-0.4	0.24	-9999	-0.58	168	168
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.42	0.25	-9999	-0.61	169	169

×

IL4-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-1.1	0.48	-10000	0	-1.4	201	201
STAT6 (cleaved dimer)	-1.2	0.51	-10000	0	-1.4	232	232
IGHG1	-0.33	0.12	-10000	0	-0.46	63	63
IGHG3	-1.1	0.46	-10000	0	-1.3	221	221
AKT1	-0.42	0.18	-10000	0	-0.75	29	29
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.31	0.17	-10000	0	-0.77	18	18
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.44	0.18	-10000	0	-0.8	17	17
THY1	-1.2	0.54	-10000	0	-1.5	205	205
MYB	-0.054	0.2	-10000	0	-0.65	31	31
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.55	0.24	-10000	0	-0.89	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.44	0.18	-10000	0	-0.76	21	21
SP1	0.011	0.011	-10000	0	-10000	0	0
INPP5D	0.011	0.038	-10000	0	-0.64	1	1
SOCS5	0.036	0.01	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-1.2	0.49	-10000	0	-1.4	222	222
SOCS1	-0.68	0.25	-10000	0	-0.84	177	177
SOCS3	-0.45	0.2	-10000	0	-0.82	30	30
FCER2	-0.79	0.35	-10000	0	-1.1	113	113
PARP14	0.008	0.066	-10000	0	-0.8	2	2
CCL17	-1.1	0.49	-10000	0	-1.4	207	207
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.35	0.15	-10000	0	-0.75	14	14
T cell proliferation	-1.2	0.52	-10000	0	-1.4	211	211
IL4R/JAK1	-1.1	0.49	-10000	0	-1.4	210	210
EGR2	-1.1	0.49	-10000	0	-1.4	205	205
JAK2	-0.031	0.019	-10000	0	-10000	0	0
JAK3	-0.023	0.18	-10000	0	-0.8	16	16
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.001	0.005	-10000	0	-10000	0	0
COL1A2	-0.59	0.36	-10000	0	-0.93	155	155
CCL26	-1.2	0.5	-10000	0	-1.5	205	205
IL4R	-1.2	0.54	-10000	0	-1.5	210	210
PTPN6	0.035	0.007	-10000	0	-10000	0	0
IL13RA2	-1.2	0.51	-10000	0	-1.5	203	203
IL13RA1	-0.031	0.019	-10000	0	-10000	0	0
IRF4	-0.3	0.35	-10000	0	-0.95	59	59
ARG1	-0.49	0.53	-10000	0	-1.3	76	76
CBL	-0.51	0.22	-10000	0	-0.89	37	37
GTF3A	0.005	0.016	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.043	0.023	-10000	0	-10000	0	0
IRF4/BCL6	-0.28	0.32	-10000	0	-0.88	59	59
CD40LG	-0.069	0.23	-10000	0	-0.66	39	39
MAPK14	-0.51	0.22	-10000	0	-0.89	37	37
mitosis	-0.41	0.17	-10000	0	-0.7	29	29
STAT6	-1.4	0.71	-10000	0	-1.8	215	215
SPI1	-0.009	0.059	-10000	0	-0.7	1	1
RPS6KB1	-0.39	0.17	-10000	0	-0.74	17	17
STAT6 (dimer)	-1.4	0.71	-10000	0	-1.8	215	215
STAT6 (dimer)/PARP14	-1.3	0.58	-10000	0	-1.6	216	216
mast cell activation	0.022	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.42	0.19	-10000	0	-0.84	21	21
FRAP1	-0.42	0.18	-10000	0	-0.74	30	30
LTA	-1.2	0.5	-10000	0	-1.4	212	212
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	1.3	0.62	1.7	215	-10000	0	215
CCL11	-1.2	0.47	-10000	0	-1.5	233	233
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.42	0.19	-10000	0	-0.79	26	26
IL2RG	-0.008	0.15	-10000	0	-0.78	11	11
IL10	-1.1	0.49	-10000	0	-1.4	201	201
IRS1	0.013	0	-10000	0	-10000	0	0
IRS2	0.009	0.053	-10000	0	-0.64	2	2
IL4	-0.21	0.069	-10000	0	-10000	0	0
IL5	-1.1	0.49	-10000	0	-1.4	203	203
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.81	0.29	-10000	0	-0.98	199	199
COL1A1	-0.73	0.35	-10000	0	-0.95	210	210
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-1.2	0.53	-10000	0	-1.5	201	201
IL2R gamma/JAK3	-0.031	0.2	-10000	0	-0.73	22	22
TFF3	-1.3	0.58	-10000	0	-1.6	223	223
ALOX15	-1.2	0.52	-10000	0	-1.5	219	219
MYBL1	0	0.1	-10000	0	-0.8	5	5
T-helper 2 cell differentiation	-0.84	0.31	-10000	0	-1	213	213
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	-0.006	0.044	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.42	0.17	-10000	0	-0.79	17	17
mol:PI-3-4-5-P3	-0.42	0.18	-10000	0	-0.75	29	29
PI3K	-0.44	0.2	-10000	0	-0.79	31	31
DOK2	0.011	0.038	-10000	0	-0.64	1	1
ETS1	0.03	0.068	-10000	0	-0.8	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.33	0.15	-10000	0	-0.73	14	14
ITGB3	-1.1	0.49	-10000	0	-1.4	201	201
PIGR	-1.4	0.59	-10000	0	-1.7	233	233
IGHE	0.056	0.043	0.27	3	-10000	0	3
MAPKKK cascade	-0.32	0.14	-10000	0	-0.71	14	14
BCL6	0.013	0.002	-10000	0	-10000	0	0
OPRM1	-1.1	0.48	-10000	0	-1.4	197	197
RETNLB	-1.1	0.49	-10000	0	-1.4	211	211
SELP	-1.2	0.52	-10000	0	-1.5	216	216
AICDA	-1.1	0.47	-10000	0	-1.4	219	219

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.72	0.5	-9999	-1.2	123	123
HDAC7	0.014	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.48	0.32	-9999	-0.87	54	54
SMAD4	0.013	0.037	-9999	-0.64	1	1
ID2	-0.72	0.5	-9999	-1.2	117	117
AP1	-0.076	0.17	-9999	-0.47	49	49
ABCG2	-0.73	0.5	-9999	-1.2	123	123
HIF1A	-0.083	0.056	-9999	-10000	0	0
TFF3	-0.86	0.57	-9999	-1.3	159	159
GATA2	0.01	0.066	-9999	-0.8	2	2
AKT1	-0.086	0.065	-9999	-10000	0	0
response to hypoxia	-0.11	0.068	-9999	-10000	0	0
MCL1	-0.72	0.5	-9999	-1.2	123	123
NDRG1	-0.72	0.5	-9999	-1.2	119	119
SERPINE1	-0.94	0.56	-9999	-1.4	163	163
FECH	-0.72	0.5	-9999	-1.2	117	117
FURIN	-0.72	0.5	-9999	-1.2	123	123
NCOA2	0.005	0.075	-9999	-0.64	4	4
EP300	-0.091	0.093	-9999	-0.37	1	1
HMOX1	-0.72	0.5	-9999	-1.2	117	117
BHLHE40	-0.72	0.5	-9999	-1.2	117	117
BHLHE41	-0.73	0.51	-9999	-1.2	136	136
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.068	0.061	-9999	-10000	0	0
ENG	-0.044	0.077	-9999	-10000	0	0
JUN	0.014	0.001	-9999	-10000	0	0
RORA	-0.72	0.5	-9999	-1.2	117	117
ABCB1	-0.2	0.32	-9999	-1.4	18	18
TFRC	-0.74	0.5	-9999	-1.2	127	127
CXCR4	-0.74	0.51	-9999	-1.2	120	120
TF	-0.93	0.56	-9999	-1.3	185	185
CITED2	-0.72	0.5	-9999	-1.2	119	119
HIF1A/ARNT	-0.84	0.64	-9999	-1.4	144	144
LDHA	-0.069	0.046	-9999	-10000	0	0
ETS1	-0.72	0.5	-9999	-1.2	117	117
PGK1	-0.72	0.5	-9999	-1.2	117	117
NOS2	-0.78	0.52	-9999	-1.3	130	130
ITGB2	-0.74	0.5	-9999	-1.2	119	119
ALDOA	-0.72	0.5	-9999	-1.2	118	118
Cbp/p300/CITED2	-0.7	0.51	-9999	-1.3	92	92
FOS	-0.091	0.24	-9999	-0.64	49	49
HK2	-0.72	0.5	-9999	-1.2	117	117
SP1	0.022	0.006	-9999	-10000	0	0
GCK	-0.18	0.22	-9999	-0.81	21	21
HK1	-0.72	0.5	-9999	-1.2	118	118
NPM1	-0.72	0.5	-9999	-1.2	117	117
EGLN1	-0.72	0.5	-9999	-1.2	117	117
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.72	0.5	-9999	-1.2	118	118
SMAD3	0.013	0.037	-9999	-0.64	1	1
EDN1	-0.1	0.18	-9999	-1.3	3	3
IGFBP1	-0.75	0.51	-9999	-1.2	123	123
VEGFA	-0.4	0.3	-9999	-0.92	11	11
HIF1A/JAB1	-0.042	0.029	-9999	-10000	0	0
CP	-0.85	0.57	-9999	-1.3	157	157
CXCL12	-0.74	0.52	-9999	-1.2	125	125
COPS5	0.013	0.005	-9999	-10000	0	0
SMAD3/SMAD4	-0.003	0.038	-9999	-0.47	2	2
BNIP3	-0.72	0.5	-9999	-1.2	118	118
EGLN3	-0.74	0.52	-9999	-1.2	127	127
CA9	-1	0.51	-9999	-1.4	197	197
TERT	-0.8	0.54	-9999	-1.3	136	136
ENO1	-0.72	0.5	-9999	-1.2	105	105
PFKL	-0.72	0.5	-9999	-1.2	117	117
NCOA1	0.013	0.003	-9999	-10000	0	0
ADM	-0.72	0.5	-9999	-1.2	117	117
ARNT	-0.083	0.055	-9999	-10000	0	0
HNF4A	-0.071	0.24	-9999	-0.8	30	30
ADFP	-0.73	0.5	-9999	-1.2	140	140
SLC2A1	-0.41	0.31	-9999	-1	14	14
LEP	-0.77	0.54	-9999	-1.3	118	118
HIF1A/ARNT/Cbp/p300	-0.5	0.34	-9999	-0.9	58	58
EPO	-0.37	0.27	-9999	-0.97	20	20
CREBBP	-0.091	0.093	-9999	-0.34	3	3
HIF1A/ARNT/Cbp/p300/HDAC7	-0.48	0.33	-9999	-0.93	34	34
PFKFB3	-0.72	0.5	-9999	-1.2	123	123
NT5E	-0.78	0.55	-9999	-1.3	124	124

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.28	0.27	-9999	-0.56	105	105
NF kappa B1 p50/RelA/I kappa B alpha	-0.28	0.23	-9999	-0.57	91	91
alphaV/beta3 Integrin/Osteopontin/Src	-0.36	0.32	-9999	-0.63	172	172
AP1	-0.38	0.31	-9999	-0.83	72	72
ILK	-0.29	0.28	-9999	-0.56	105	105
bone resorption	-0.24	0.22	-9999	-0.78	9	9
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.27	0.24	-9999	-0.58	36	36
ITGAV	0.004	0.077	-9999	-0.76	3	3
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.002	0.027	-9999	-0.47	1	1
alphaV/beta3 Integrin/Osteopontin	-0.34	0.29	-9999	-0.57	176	176
MAP3K1	-0.3	0.28	-9999	-0.52	176	176
JUN	0.012	0.002	-9999	-10000	0	0
MAPK3	-0.3	0.29	-9999	-0.53	176	176
MAPK1	-0.3	0.29	-9999	-0.6	105	105
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.28	0.28	-9999	-0.56	103	103
ITGB3	-0.02	0.15	-9999	-0.77	12	12
NFKBIA	-0.3	0.28	-9999	-0.63	91	91
FOS	-0.094	0.24	-9999	-0.64	49	49
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.44	0.4	-9999	-0.83	134	134
NF kappa B1 p50/RelA	-0.3	0.24	-9999	-0.61	91	91
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.03	0.13	-9999	-0.63	14	14
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.29	0.28	-9999	-0.52	176	176
VAV3	-0.29	0.28	-9999	-0.56	115	115
MAP3K14	-0.31	0.29	-9999	-0.54	176	176
ROCK2	0.011	0.038	-9999	-0.64	1	1
SPP1	-0.45	0.41	-9999	-0.81	171	171
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.28	0.24	-9999	-0.6	52	52
MMP2	-0.34	0.34	-9999	-0.78	87	87

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.18	0.31	-9999	-0.63	82	82
alphaM/beta2 Integrin/GPIbA	-0.089	0.24	-9999	-0.7	37	37
alphaM/beta2 Integrin/proMMP-9	-0.46	0.32	-9999	-0.61	231	231
PLAUR	-0.022	0.16	-9999	-0.8	13	13
HMGB1	0.01	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.073	0.22	-9999	-0.69	30	30
AGER	0.005	0.067	-9999	-0.8	2	2
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	0.013	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.086	0.2	-9999	-0.62	31	31
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.61	0.35	-9999	-0.8	230	230
CYR61	0.009	0.06	-9999	-0.72	2	2
TLN1	0.011	0.047	-9999	-0.8	1	1
Rap1/GTP	-0.19	0.16	-9999	-0.51	37	37
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.25	-9999	-0.64	54	54
MYH2	-0.42	0.26	-9999	-0.62	165	165
MST1R	0	0.091	-9999	-0.64	6	6
leukocyte activation during inflammatory response	-0.087	0.22	-9999	-0.57	44	44
APOB	-0.01	0.13	-9999	-0.78	8	8
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.15	0.33	-9999	-0.8	61	61
JAM3	0.011	0.047	-9999	-0.8	1	1
GP1BA	-0.017	0.15	-9999	-0.79	11	11
alphaM/beta2 Integrin/CTGF	-0.074	0.22	-9999	-0.68	31	31
alphaM/beta2 Integrin	-0.22	0.2	-9999	-0.44	108	108
JAM3 homodimer	0.011	0.047	-9999	-0.8	1	1
ICAM2	0.009	0.053	-9999	-0.64	2	2
ICAM1	-0.032	0.19	-9999	-0.8	17	17
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.22	0.2	-9999	-0.44	108	108
cell adhesion	-0.089	0.24	-9999	-0.69	37	37
NFKB1	-0.044	0.24	-9999	-0.82	15	15
THY1	-0.26	0.38	-9999	-0.8	101	101
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.032	0.13	-9999	-0.53	18	18
alphaM/beta2 Integrin/LRP/tPA	-0.076	0.21	-9999	-0.62	36	36
IL6	-0.072	0.31	-9999	-0.79	39	39
ITGB2	-0.024	0.16	-9999	-0.79	13	13
elevation of cytosolic calcium ion concentration	-0.29	0.33	-9999	-0.57	153	153
alphaM/beta2 Integrin/JAM2/JAM3	-0.075	0.21	-9999	-0.64	31	31
JAM2	-0.004	0.1	-9999	-0.64	8	8
alphaM/beta2 Integrin/ICAM1	-0.094	0.24	-9999	-0.66	39	39
alphaM/beta2 Integrin/uPA/Plg	-0.28	0.31	-9999	-0.55	151	151
RhoA/GTP	-0.27	0.22	-9999	-0.54	92	92
positive regulation of phagocytosis	-0.17	0.19	-9999	-0.61	33	33
Ron/MSP	-0.014	0.083	-9999	-0.49	9	9
alphaM/beta2 Integrin/uPAR/uPA	-0.29	0.34	-9999	-0.57	153	153
alphaM/beta2 Integrin/uPAR	-0.092	0.25	-9999	-0.7	38	38
PLAU	-0.34	0.4	-9999	-0.8	133	133
PLAT	-0.008	0.13	-9999	-0.8	8	8
actin filament polymerization	-0.4	0.24	-9999	-0.58	165	165
MST1	0.006	0.071	-9999	-0.7	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.089	0.22	-9999	-0.58	44	44
TNF	-0.048	0.26	-9999	-0.77	25	25
RAP1B	0.011	0.047	-9999	-0.8	1	1
alphaM/beta2 Integrin/uPA	-0.3	0.33	-9999	-0.6	151	151
fibrinolysis	-0.27	0.3	-9999	-0.55	151	151
HCK	0.004	0.084	-9999	-0.72	4	4
dendritic cell antigen processing and presentation	-0.22	0.2	-9999	-0.44	108	108
VTN	-0.059	0.23	-9999	-0.8	27	27
alphaM/beta2 Integrin/CYR61	-0.074	0.22	-9999	-0.68	31	31
LPA	-0.019	0.14	-9999	-0.8	10	10
LRP1	0.013	0	-9999	-10000	0	0
cell migration	-0.52	0.38	-9999	-0.66	236	236
FN1	-0.44	0.4	-9999	-0.8	170	170
alphaM/beta2 Integrin/Thy1	-0.24	0.35	-9999	-0.65	112	112
MPO	-0.01	0.12	-9999	-0.67	10	10
KNG1	-0.005	0.093	-9999	-0.8	4	4
RAP1/GDP	-0.002	0.031	-9999	-0.54	1	1
ROCK1	-0.24	0.21	-9999	-0.5	92	92
ELA2	0	0	-9999	-10000	0	0
PLG	0.002	0.005	-9999	-10000	0	0
CTGF	0.009	0.053	-9999	-0.64	2	2
alphaM/beta2 Integrin/Hck	-0.077	0.22	-9999	-0.68	32	32
ITGAM	-0.061	0.23	-9999	-0.79	27	27
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.23	-9999	-0.66	30	30
HP	-0.24	0.32	-9999	-0.65	116	116
leukocyte adhesion	-0.2	0.27	-9999	-0.79	34	34
SELP	-0.1	0.25	-9999	-0.64	54	54

×

Glypican 2 network

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
MDK	-0.01	0.14	-9999	-0.78	9	9
GPC2	-0.12	0.3	-9999	-0.8	50	50
GPC2/Midkine	-0.12	0.25	-9999	-0.63	57	57
neuron projection morphogenesis	-0.12	0.25	-9999	-0.63	57	57

×

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	-0.55	0.44	-10000	0	-1.2	60	60
IL23A	-0.53	0.42	-10000	0	-1.2	50	50
NF kappa B1 p50/RelA/I kappa B alpha	-0.53	0.4	-10000	0	-1.1	72	72
positive regulation of T cell mediated cytotoxicity	-0.59	0.47	-10000	0	-1.2	78	78
ITGA3	-0.53	0.42	-10000	0	-1.1	59	59
IL17F	-0.36	0.27	-10000	0	-0.75	41	41
IL12B	-0.094	0.26	-10000	0	-0.84	33	33
STAT1 (dimer)	-0.59	0.47	-10000	0	-1.2	83	83
CD4	-0.52	0.4	-10000	0	-1.1	56	56
IL23	-0.55	0.42	-10000	0	-1.1	64	64
IL23R	-0.084	0.11	-10000	0	-0.7	6	6
IL1B	-0.56	0.44	-10000	0	-1.2	72	72
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.7	0.44	-10000	0	-1.2	112	112
TYK2	-0.001	0.012	-10000	0	-10000	0	0
STAT4	-0.002	0.11	-10000	0	-0.78	6	6
STAT3	0.013	0.001	-10000	0	-10000	0	0
IL18RAP	-0.007	0.12	-10000	0	-0.71	8	8
IL12RB1	-0.088	0.26	-10000	0	-0.83	32	32
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.073	0.2	-10000	0	-0.65	32	32
IL23R/JAK2	-0.099	0.11	-10000	0	-0.74	4	4
positive regulation of chronic inflammatory response	-0.59	0.47	-10000	0	-1.2	78	78
natural killer cell activation	0.008	0.009	0.059	6	-10000	0	6
JAK2	0.003	0.014	-10000	0	-10000	0	0
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
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	-0.52	0.4	-10000	0	-1.1	64	64
ALOX12B	-0.62	0.46	-10000	0	-1.2	93	93
CXCL1	-0.56	0.44	-10000	0	-1.2	63	63
T cell proliferation	-0.59	0.47	-10000	0	-1.2	78	78
NFKBIA	0.01	0.003	-10000	0	-10000	0	0
IL17A	-0.28	0.22	-10000	0	-0.62	17	17
PI3K	-0.54	0.41	-10000	0	-1	90	90
IFNG	-0.03	0.047	0.13	5	-0.11	55	60
STAT3 (dimer)	-0.51	0.39	-10000	0	-1	74	74
IL18R1	0.008	0.061	-10000	0	-0.73	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.33	0.26	-10000	0	-0.8	32	32
IL18/IL18R	-0.004	0.12	-10000	0	-0.62	5	5
macrophage activation	-0.027	0.015	-10000	0	-0.045	28	28
TNF	-0.55	0.44	-10000	0	-1.2	53	53
STAT3/STAT4	-0.55	0.41	-10000	0	-1.1	84	84
STAT4 (dimer)	-0.57	0.45	-10000	0	-1.2	75	75
IL18	-0.009	0.12	-10000	0	-0.64	10	10
IL19	-0.66	0.52	-10000	0	-1.3	107	107
STAT5A (dimer)	-0.56	0.45	-10000	0	-1.2	74	74
STAT1	-0.048	0.22	-10000	0	-0.8	23	23
SOCS3	0.011	0.038	-10000	0	-0.64	1	1
CXCL9	-0.65	0.47	-10000	0	-1.1	110	110
MPO	-0.54	0.42	-10000	0	-1.2	60	60
positive regulation of humoral immune response	-0.59	0.47	-10000	0	-1.2	78	78
IL23/IL23R/JAK2/TYK2	-0.61	0.51	-10000	0	-1.3	78	78
IL6	-0.56	0.46	-10000	0	-1.2	63	63
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.005	0.047	-10000	0	-0.79	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.009	0.059	6	-10000	0	6
CD3E	-0.52	0.41	-10000	0	-1.1	59	59
keratinocyte proliferation	-0.59	0.47	-10000	0	-1.2	78	78
NOS2	-0.57	0.43	-10000	0	-1.1	74	74

×

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	-0.31	0.31	-9999	-0.56	171	171
EPHB2	-0.17	0.34	-9999	-0.8	67	67
Syndecan-2/TACI	-0.072	0.21	-9999	-0.54	51	51
LAMA1	-0.37	0.41	-9999	-0.8	143	143
Syndecan-2/alpha2 ITGB1	-0.15	0.22	-9999	-0.46	97	97
HRAS	0.013	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.023	0.11	-9999	-0.54	13	13
ITGA5	-0.27	0.39	-9999	-0.8	105	105
BAX	0.02	0.11	-9999	-0.49	13	13
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.021	0.098	-9999	-0.48	13	13
LAMA3	-0.22	0.37	-9999	-0.8	87	87
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.009	0.06	-9999	-0.72	2	2
Syndecan-2/MMP2	-0.11	0.26	-9999	-0.59	66	66
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.002	0.035	-9999	-0.61	1	1
dendrite morphogenesis	-0.12	0.25	-9999	-0.55	77	77
Syndecan-2/GM-CSF	-0.28	0.3	-9999	-0.55	162	162
determination of left/right symmetry	-0.005	0.13	-9999	-0.61	13	13
Syndecan-2/PKC delta	0.003	0.11	-9999	-0.53	13	13
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.25	0.28	-9999	-0.5	162	162
MAPK1	-0.25	0.28	-9999	-0.5	162	162
Syndecan-2/RACK1	-0.019	0.092	-9999	-0.45	13	13
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.005	0.13	-9999	-0.61	13	13
ITGA2	0.013	0	-9999	-10000	0	0
MAPK8	0.011	0.12	-9999	-0.54	14	14
Syndecan-2/alpha2/beta1 Integrin	-0.23	0.25	-9999	-0.48	144	144
Syndecan-2/Kininogen	-0.019	0.13	-9999	-0.56	16	16
ITGB1	0.011	0.047	-9999	-0.8	1	1
SRC	0.02	0.094	-9999	-0.42	13	13
Syndecan-2/CASK/Protein 4.1	-0.021	0.098	-9999	-0.49	13	13
extracellular matrix organization	0.001	0.12	-9999	-0.56	13	13
actin cytoskeleton reorganization	-0.3	0.3	-9999	-0.56	171	171
Syndecan-2/Caveolin-2/Ras	-0.023	0.1	-9999	-0.47	15	15
Syndecan-2/Laminin alpha3	-0.16	0.27	-9999	-0.55	96	96
Syndecan-2/RasGAP	-0.018	0.087	-9999	-0.43	13	13
alpha5/beta1 Integrin	-0.22	0.29	-9999	-0.61	106	106
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.12	0.25	-9999	-0.55	77	77
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.027	0.092	-9999	-0.41	13	13
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.093	0.27	-9999	-0.8	39	39
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.002	0.035	-9999	-0.61	1	1
Syndecan-2/Synbindin	0.003	0.11	-9999	-0.53	13	13
TGFB1	0.011	0.047	-9999	-0.8	1	1
CASP3	0.014	0.1	-9999	-0.48	13	13
FN1	-0.44	0.4	-9999	-0.8	170	170
Syndecan-2/IL8	-0.12	0.26	-9999	-0.56	73	73
SDC2	-0.005	0.13	-9999	-0.61	13	13
KNG1	-0.005	0.093	-9999	-0.8	4	4
Syndecan-2/Neurofibromin	0.003	0.11	-9999	-0.53	13	13
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.41	0.41	-9999	-0.8	157	157
Syndecan-2/TGFB1	0.001	0.12	-9999	-0.56	13	13
Syndecan-2/Syntenin/PI-4-5-P2	-0.021	0.098	-9999	-0.49	13	13
Syndecan-2/Ezrin	-0.02	0.097	-9999	-0.48	13	13
PRKACA	0.014	0.1	-9999	-0.48	13	13
angiogenesis	-0.11	0.26	-9999	-0.56	73	73
MMP2	-0.15	0.33	-9999	-0.8	61	61
IL8	-0.16	0.33	-9999	-0.8	65	65
calcineurin-NFAT signaling pathway	-0.071	0.21	-9999	-0.54	51	51

×

Endothelins

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
AKT1	-0.23	0.3	-10000	0	-0.7	46	46
PTK2B	0.013	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.091	0.22	-10000	0	-0.68	20	20
EDN1	-0.14	0.2	-10000	0	-0.44	21	21
EDN3	-0.31	0.32	-10000	0	-0.64	147	147
EDN2	-0.09	0.26	-10000	0	-0.71	43	43
HRAS/GDP	-0.086	0.18	-10000	0	-0.54	10	10
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.083	0.14	-10000	0	-0.39	18	18
ADCY4	-0.23	0.25	-10000	0	-0.61	60	60
ADCY5	-0.31	0.26	-10000	0	-0.64	91	91
ADCY6	-0.24	0.25	-10000	0	-0.63	62	62
ADCY7	-0.23	0.25	-10000	0	-0.61	60	60
ADCY1	-0.25	0.26	-10000	0	-0.64	67	67
ADCY2	-0.34	0.26	-10000	0	-0.64	104	104
ADCY3	-0.23	0.25	-10000	0	-0.61	60	60
ADCY8	-0.25	0.26	-10000	0	-0.63	68	68
ADCY9	-0.23	0.25	-10000	0	-0.61	60	60
arachidonic acid secretion	-0.12	0.23	-10000	0	-0.55	41	41
ETB receptor/Endothelin-1/Gq/GTP	-0.08	0.14	-10000	0	-0.44	17	17
GNAO1	0.009	0.06	-10000	0	-0.72	2	2
HRAS	0.012	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.16	0.34	0.34	64	-0.66	47	111
ETA receptor/Endothelin-1/Gs/GTP	-0.2	0.33	0.32	54	-0.64	61	115
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.51	0.48	-10000	0	-0.86	190	190
EDNRB	-0.026	0.072	-10000	0	-0.64	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.3	0.4	-10000	0	-0.96	58	58
CYSLTR1	-0.27	0.33	-10000	0	-0.75	60	60
SLC9A1	-0.095	0.16	-10000	0	-0.39	2	2
mol:GDP	-0.098	0.18	-10000	0	-0.49	22	22
SLC9A3	-0.27	0.35	-10000	0	-0.76	82	82
RAF1	-0.12	0.2	-10000	0	-0.54	28	28
JUN	-0.069	0.17	-10000	0	-0.66	1	1
JAK2	-0.23	0.3	-10000	0	-0.71	44	44
mol:IP3	-0.1	0.16	-10000	0	-0.5	20	20
ETA receptor/Endothelin-1	-0.22	0.41	0.4	67	-0.77	50	117
PLCB1	0.009	0.038	-10000	0	-0.64	1	1
PLCB2	0.01	0.038	-10000	0	-0.64	1	1
ETA receptor/Endothelin-3	-0.3	0.27	-10000	0	-0.55	147	147
FOS	-0.18	0.37	-10000	0	-0.96	50	50
Gai/GDP	0.009	0.07	-10000	0	-0.6	2	2
CRK	0.013	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.25	0.28	-10000	0	-0.66	59	59
BCAR1	0.014	0	-10000	0	-10000	0	0
PRKCB1	-0.1	0.16	-10000	0	-0.47	22	22
GNAQ	0.013	0.007	-10000	0	-10000	0	0
GNAZ	-0.004	0.11	-10000	0	-0.73	7	7
GNAL	-0.06	0.21	-10000	0	-0.64	34	34
Gs family/GDP	-0.15	0.16	-10000	0	-0.51	29	29
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.17	-10000	0	-0.45	20	20
MAPK14	-0.048	0.12	-10000	0	-0.6	3	3
TRPC6	-0.095	0.22	-10000	0	-0.72	20	20
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.011	0.038	-10000	0	-0.64	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.06	0.12	-10000	0	-0.5	6	6
ETB receptor/Endothelin-2	-0.091	0.19	-10000	0	-0.54	46	46
ETB receptor/Endothelin-3	-0.25	0.24	-10000	0	-0.49	149	149
ETB receptor/Endothelin-1	-0.12	0.18	-10000	0	-0.58	6	6
MAPK3	-0.16	0.32	-10000	0	-0.82	50	50
MAPK1	-0.16	0.32	-10000	0	-0.82	50	50
Rac1/GDP	-0.085	0.17	-10000	0	-0.57	8	8
cAMP biosynthetic process	-0.27	0.23	-10000	0	-0.59	72	72
MAPK8	-0.088	0.19	-10000	0	-0.57	14	14
SRC	0.013	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.028	0.089	-10000	0	-0.46	1	1
p130Cas/CRK/Src/PYK2	-0.092	0.19	-10000	0	-0.57	14	14
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.088	0.18	-10000	0	-0.55	10	10
COL1A2	-0.41	0.47	-10000	0	-0.85	155	155
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.14	0.23	-10000	0	-0.61	43	43
mol:DAG	-0.1	0.16	-10000	0	-0.5	20	20
MAP2K2	-0.13	0.25	-10000	0	-0.63	44	44
MAP2K1	-0.13	0.25	-10000	0	-0.63	44	44
EDNRA	-0.12	0.18	-10000	0	-0.61	1	1
positive regulation of muscle contraction	-0.19	0.26	-10000	0	-0.63	43	43
Gq family/GDP	-0.11	0.17	-10000	0	-0.6	10	10
HRAS/GTP	-0.11	0.18	-10000	0	-0.48	28	28
PRKCH	-0.094	0.16	-10000	0	-0.48	19	19
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.096	0.16	-10000	0	-0.48	19	19
PRKCB	-0.1	0.17	-10000	0	-0.51	26	26
PRKCE	-0.094	0.16	-10000	0	-0.48	19	19
PRKCD	-0.095	0.16	-10000	0	-0.48	19	19
PRKCG	-0.14	0.21	-10000	0	-0.55	41	41
regulation of vascular smooth muscle contraction	-0.2	0.43	-10000	0	-1.1	50	50
PRKCQ	-0.1	0.17	-10000	0	-0.5	24	24
PLA2G4A	-0.13	0.24	-10000	0	-0.6	42	42
GNA14	-0.095	0.24	-10000	0	-0.64	50	50
GNA15	0.012	0.006	-10000	0	-10000	0	0
GNA12	0.008	0.066	-10000	0	-0.8	2	2
GNA11	0.012	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.16	0.34	0.34	64	-0.67	43	107
MMP1	-0.55	0.23	-10000	0	-0.63	271	271

×

TCGA08_p53

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
CDKN2A	-0.24	0.3	-10000	0	-0.59	124	124
TP53	-0.071	0.088	-10000	0	-0.41	3	3
Senescence	-0.071	0.088	-10000	0	-0.41	3	3
Apoptosis	-0.071	0.088	-10000	0	-0.41	3	3
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.12	0.15	0.3	124	-10000	0	124
MDM4	0.013	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.008	0.06	-9999	-0.46	4	4
RGS9BP	-0.013	0.13	-9999	-0.64	12	12
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.2	0.26	-9999	-0.54	112	112
mol:ADP	-0.059	0.2	-9999	-0.62	35	35
GNAT2	0.012	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.019	0.085	-9999	-0.4	14	14
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.081	0.26	-9999	-0.8	35	35
CNGB3	-0.29	0.39	-9999	-0.8	112	112
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.3	0.33	-9999	-0.58	162	162
Cone PDE6	-0.016	0.073	-9999	-0.46	1	1
Cone Metarhodopsin II	-0.058	0.16	-9999	-0.5	35	35
Na + (4 Units)	-0.31	0.32	-9999	-0.58	162	162
GNAT2/GDP	-0.016	0.072	-9999	-0.45	1	1
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.005	-9999	-10000	0	0
Cone Transducin	-0.009	0.063	-9999	-0.49	4	4
SLC24A2	-0.21	0.36	-9999	-0.8	83	83
GNB3/GNGT2	-0.011	0.079	-9999	-0.56	6	6
GNB3	0.001	0.096	-9999	-0.74	5	5
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.01	0.006	-9999	-10000	0	0
ARR3	0.001	0.004	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.2	0.26	-9999	-0.54	112	112
mol:Pi	-0.019	0.085	-9999	-0.4	14	14
Cone CNG Channel	-0.16	0.22	-9999	-0.45	112	112
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.21	0.36	-9999	-0.8	83	83
RGS9	0.009	0.06	-9999	-0.72	2	2
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	0.011	0.047	-9999	-0.8	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.014	0.08	-9999	-0.47	9	9
Necdin/E2F1	-0.041	0.15	-9999	-0.59	21	21
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.13	0.2	-9999	-0.45	73	73
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.25	-9999	-0.54	85	85
NT-4/5 (dimer)/p75(NTR)	-0.027	0.12	-9999	-0.55	15	15
IKBKB	0.013	0	-9999	-10000	0	0
AKT1	-0.083	0.21	-9999	-0.44	72	72
IKBKG	0.013	0	-9999	-10000	0	0
BDNF	-0.042	0.2	-9999	-0.72	23	23
MGDIs/NGR/p75(NTR)/LINGO1	-0.073	0.2	-9999	-0.61	33	33
FURIN	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.069	0.17	-9999	-0.55	21	21
LINGO1	-0.046	0.21	-9999	-0.8	22	22
Sortilin/TRAF6/NRIF	-0.009	0.051	-9999	-10000	0	0
proBDNF (dimer)	-0.042	0.2	-9999	-0.72	23	23
NTRK1	-0.062	0.24	-9999	-0.8	28	28
RTN4R	-0.005	0.12	-9999	-0.8	7	7
neuron apoptosis	-0.065	0.18	-9999	-0.59	12	12
IRAK1	0.013	0	-9999	-10000	0	0
SHC1	-0.12	0.24	-9999	-0.53	72	72
ARHGDIA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.026	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.14	0.22	-9999	-0.49	73	73
MAGEH1	0.011	0.047	-9999	-0.8	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.14	0.22	-9999	-0.5	74	74
Mammalian IAPs/DIABLO	-0.031	0.14	-9999	-0.6	16	16
proNGF (dimer)	-0.16	0.33	-9999	-0.8	66	66
MAGED1	0.011	0.038	-9999	-0.64	1	1
APP	0.013	0	-9999	-10000	0	0
NT-4/5 (dimer)	0.013	0.001	-9999	-10000	0	0
ZNF274	0.013	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.12	0.19	-9999	-0.45	72	72
NGF	-0.16	0.34	-9999	-0.8	66	66
cell cycle arrest	-0.12	0.22	-9999	-0.49	72	72
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.038	0.13	-9999	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.023	0.1	-9999	-0.53	8	8
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.14	0.23	-9999	-0.53	72	72
PSENEN	0.011	0.047	-9999	-0.8	1	1
mol:ceramide	-0.11	0.22	-9999	-0.48	72	72
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.017	0.11	-9999	-0.6	1	1
p75(NTR)/beta APP	-0.027	0.12	-9999	-0.55	15	15
BEX1	-0.03	0.18	-9999	-0.8	15	15
mol:GDP	-0.12	0.24	-9999	-0.52	81	81
NGF (dimer)	-0.19	0.26	-9999	-0.54	96	96
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.066	0.18	-9999	-0.56	33	33
PIK3R1	0.013	0	-9999	-10000	0	0
RAC1/GTP	-0.12	0.2	-9999	-0.46	72	72
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.14	0.23	-9999	-0.53	72	72
RHOB	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.034	0.14	-9999	-0.61	17	17
NT3 (dimer)	-0.18	0.3	-9999	-0.64	90	90
TP53	-0.015	0.16	-9999	-0.63	3	3
PRDM4	-0.11	0.23	-9999	-0.48	72	72
BDNF (dimer)	-0.44	0.3	-9999	-0.59	222	222
PIK3CA	0.013	0	-9999	-10000	0	0
SORT1	-0.006	0.11	-9999	-0.64	9	9
activation of caspase activity	-0.12	0.2	-9999	-0.45	73	73
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.14	0.21	-9999	-0.48	72	72
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	-0.07	0.19	-9999	-0.52	13	13
DIABLO	0.013	0	-9999	-10000	0	0
SMPD2	-0.11	0.23	-9999	-0.48	72	72
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.15	0.23	-9999	-0.51	89	89
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.17	0.24	-9999	-0.49	102	102
MAPK8	-0.06	0.19	-9999	-0.52	10	10
MAPK9	-0.058	0.19	-9999	-0.52	9	9
APAF1	0.013	0	-9999	-10000	0	0
NTF3	-0.18	0.3	-9999	-0.64	90	90
NTF4	0.013	0.001	-9999	-10000	0	0
NDN	0.005	0.075	-9999	-0.64	4	4
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.11	0.18	-9999	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.01	0.06	-9999	-10000	0	0
RhoA-B-C/GTP	-0.14	0.23	-9999	-0.52	72	72
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.058	0.14	-9999	-0.47	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.063	0.15	-9999	-0.5	21	21
PRKACB	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.041	0.14	-9999	-0.54	23	23
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.024	0.17	-9999	-0.8	14	14
BIRC2	-0.003	0.11	-9999	-0.8	6	6
neuron projection morphogenesis	-0.11	0.21	-9999	-0.44	73	73
BAD	-0.053	0.18	-9999	-0.49	9	9
RIPK2	0.013	0	-9999	-10000	0	0
NGFR	-0.023	0.16	-9999	-0.73	15	15
CYCS	-0.095	0.22	-9999	-0.45	72	72
ADAM17	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.12	0.21	-9999	-0.48	72	72
BCL2L11	-0.053	0.18	-9999	-0.49	9	9
BDNF (dimer)/p75(NTR)	-0.068	0.18	-9999	-0.54	38	38
PI3K	-0.12	0.21	-9999	-0.48	72	72
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.14	0.21	-9999	-0.48	72	72
NDNL2	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.16	0.26	-9999	-0.6	81	81
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.14	0.21	-9999	-0.48	72	72
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.011	0.038	-9999	-0.64	1	1
PLG	0.002	0.005	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.11	0.22	-9999	-0.6	17	17
SQSTM1	0.013	0	-9999	-10000	0	0
NGFRAP1	0.011	0.047	-9999	-0.8	1	1
CASP3	-0.046	0.17	-9999	-0.45	9	9
E2F1	-0.032	0.19	-9999	-0.8	17	17
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.12	0.18	-9999	-0.73	6	6
NGF (dimer)/TRKA	-0.19	0.3	-9999	-0.64	88	88
MMP7	-0.13	0.3	-9999	-0.76	55	55
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.12	0.2	-9999	-0.45	72	72
MMP3	-0.55	0.38	-9999	-0.8	210	210
APAF-1/Caspase 9	-0.11	0.17	-9999	-0.69	8	8

×

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 +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.005	0.054	-9999	-0.55	3	3
PDE6G/GNAT1/GTP	-0.021	0.11	-9999	-0.54	12	12
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.007	0.007	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.46	0.3	-9999	-0.78	123	123
mol:Na +	-0.32	0.26	-9999	-0.79	38	38
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.019	0.085	-9999	-0.4	14	14
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.33	0.27	-9999	-0.83	38	38
CNGB1	-0.45	0.4	-9999	-0.8	172	172
RDH5	0.011	0.038	-9999	-0.64	1	1
SAG	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.29	0.26	-9999	-0.76	38	38
Na + (4 Units)	-0.3	0.24	-9999	-0.73	38	38
RGS9	0.009	0.06	-9999	-0.72	2	2
GNB1/GNGT1	-0.1	0.23	-9999	-0.61	51	51
GNAT1/GDP	-0.016	0.072	-9999	-0.45	1	1
GUCY2D	-0.027	0.18	-9999	-0.8	15	15
GNGT1	-0.12	0.3	-9999	-0.8	51	51
GUCY2F	0	0.047	-9999	-0.8	1	1
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.21	0.23	-9999	-0.63	34	34
mol:11-cis-retinal	0.011	0.037	-9999	-0.64	1	1
mol:cGMP	-0.082	0.18	-9999	-0.49	48	48
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.008	0.066	-9999	-0.58	4	4
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	-0.038	0.18	-9999	-0.64	24	24
Metarhodopsin II	-0.005	0.049	-9999	-0.5	3	3
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.085	0.19	-9999	-0.52	47	47
RGS9BP	-0.013	0.13	-9999	-0.64	12	12
Metarhodopsin II/Transducin	-0.034	0.11	-9999	-0.27	38	38
GCAP Family/Ca ++	-0.062	0.16	-9999	-0.49	38	38
PDE6A/B	-0.28	0.27	-9999	-0.51	166	166
mol:Pi	-0.019	0.085	-9999	-0.4	14	14
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.083	0.18	-9999	-0.49	51	51
PDE6B	-0.046	0.2	-9999	-0.71	25	25
PDE6A	-0.32	0.33	-9999	-0.64	155	155
PDE6G	-0.019	0.16	-9999	-0.8	12	12
RHO	-0.004	0.08	-9999	-0.8	3	3
PDE6	-0.22	0.22	-9999	-0.68	30	30
GUCA1A	-0.079	0.26	-9999	-0.8	34	34
GC2/GCAP Family	-0.063	0.17	-9999	-0.5	35	35
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.003	0.083	-9999	-0.64	5	5

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.22	0.36	-9999	-1.1	26	26
PCK1	-0.54	0.64	-9999	-1.4	110	110
HNF4A	-0.27	0.43	-9999	-1.2	32	32
KCNJ11	-0.32	0.49	-9999	-1.2	55	55
AKT1	-0.076	0.14	-9999	-10000	0	0
response to starvation	-0.003	0.023	-9999	-10000	0	0
DLK1	-0.45	0.58	-9999	-1.2	103	103
NKX2-1	-0.076	0.33	-9999	-0.84	27	27
ACADM	-0.22	0.36	-9999	-1.1	26	26
TAT	-0.15	0.23	-9999	-0.82	10	10
CEBPB	0.015	0.002	-9999	-10000	0	0
CEBPA	0.01	0.053	-9999	-0.64	2	2
TTR	-0.29	0.3	-9999	-0.88	35	35
PKLR	-0.26	0.41	-9999	-1	45	45
APOA1	-0.26	0.41	-9999	-1.2	23	23
CPT1C	-0.22	0.36	-9999	-1.1	26	26
ALAS1	-0.082	0.16	-9999	-10000	0	0
TFRC	-0.22	0.31	-9999	-0.92	26	26
FOXF1	0.014	0.11	-9999	-0.7	5	5
NF1	0.021	0	-9999	-10000	0	0
HNF1A (dimer)	-0.001	0.12	-9999	-0.8	6	6
CPT1A	-0.22	0.36	-9999	-1.1	25	25
HMGCS1	-0.22	0.36	-9999	-1.1	26	26
NR3C1	0.016	0.032	-9999	-10000	0	0
CPT1B	-0.22	0.38	-9999	-1.1	27	27
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.026	-9999	-10000	0	0
GCK	-0.25	0.38	-9999	-1.1	32	32
CREB1	-0.041	0.086	-9999	-10000	0	0
IGFBP1	-0.11	0.22	-9999	-0.82	16	16
PDX1	-0.11	0.22	-9999	-0.8	13	13
UCP2	-0.22	0.37	-9999	-1.1	25	25
ALDOB	-0.25	0.4	-9999	-1.1	32	32
AFP	-0.21	0.24	-9999	-0.7	31	31
BDH1	-0.22	0.36	-9999	-1.1	25	25
HADH	-0.23	0.38	-9999	-1.1	23	23
F2	-0.28	0.43	-9999	-1.3	26	26
HNF1A	-0.001	0.12	-9999	-0.8	6	6
G6PC	-0.064	0.14	-9999	-10000	0	0
SLC2A2	-0.13	0.22	-9999	-0.83	3	3
INS	-0.005	0.035	-9999	-10000	0	0
FOXA1	-0.23	0.33	-9999	-0.65	113	113
FOXA3	-0.15	0.3	-9999	-0.92	33	33
FOXA2	-0.27	0.44	-9999	-1.2	31	31
ABCC8	-0.24	0.39	-9999	-1.1	25	25
ALB	-0.25	0.3	-9999	-0.81	49	49

×

Effects of Botulinum toxin

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
STX1A	0	0.089	-9999	-0.62	6	6
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.066	0.16	-9999	-0.47	42	42
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.16	0.25	-9999	-0.51	98	98
RAB3GAP2/RIMS1/UNC13B	-0.055	0.14	-9999	-0.4	42	42
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	-0.08	0.22	-9999	-0.64	41	41
mol:ACh	0.002	0.032	-9999	-0.12	20	20
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.052	0.11	-9999	-0.44	1	1
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.16	0.25	-9999	-0.51	98	98
UNC13B	0.011	0.038	-9999	-0.64	1	1
CHRNA1	-0.23	0.35	-9999	-0.73	98	98
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.15	0.26	-9999	-0.56	84	84
SNAP25	-0.006	0.064	-9999	-0.3	14	14
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.21	0.36	-9999	-0.79	84	84
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.008	0.077	-9999	-0.54	6	6
STX1A/SNAP25 fragment 1/VAMP2	-0.052	0.11	-9999	-0.44	1	1

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.24	0.28	-9999	-0.84	29	29
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.062	0.22	-9999	-0.71	31	31
SMAD9	-0.07	0.16	-9999	-0.71	15	15
SMAD4	0.011	0.038	-9999	-0.64	1	1
SMAD5	-0.053	0.16	-9999	-0.52	18	18
BMP7/USAG1	-0.17	0.27	-9999	-0.55	94	94
SMAD5/SKI	-0.043	0.15	-9999	-0.51	14	14
SMAD1	0.041	0.029	-9999	-10000	0	0
BMP2	-0.016	0.15	-9999	-0.79	11	11
SMAD1/SMAD1/SMAD4	-0.001	0.017	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.077	0.25	-9999	-0.77	35	35
BMPR1A-1B/BAMBI	-0.074	0.18	-9999	-0.5	45	45
AHSG	-0.041	0.2	-9999	-0.8	19	19
CER1	-0.007	0.092	-9999	-0.8	4	4
BMP2-4/CER1	-0.033	0.12	-9999	-0.5	19	19
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.095	0.21	-9999	-0.59	30	30
BMP2-4 (homodimer)	-0.03	0.13	-9999	-0.56	16	16
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.057	0.15	-9999	-0.48	30	30
RGMA	-0.071	0.22	-9999	-0.64	39	39
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.094	0.2	-9999	-0.54	31	31
BMP2-4/USAG1	-0.14	0.22	-9999	-0.45	97	97
SMAD6/SMURF1/SMAD5	-0.043	0.15	-9999	-0.51	14	14
SOSTDC1	-0.18	0.31	-9999	-0.67	85	85
BMP7/BMPR2/BMPR1A-1B	-0.078	0.17	-9999	-0.5	30	30
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.006	0.076	-9999	-0.75	3	3
HFE2	-0.17	0.29	-9999	-0.64	81	81
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.042	0.14	-9999	-0.54	20	20
SMAD5/SMAD5/SMAD4	-0.044	0.15	-9999	-0.52	15	15
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.097	0.15	-9999	-0.57	15	15
BMP7 (homodimer)	-0.035	0.17	-9999	-0.65	22	22
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.044	0.16	-9999	-0.61	22	22
SMAD1/SKI	0.047	0.028	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.058	0.17	-9999	-0.52	34	34
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.41	0.41	-9999	-0.8	158	158
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.068	0.19	-9999	-0.58	35	35
CHRDL1	-0.3	0.33	-9999	-0.64	143	143
ENDOFIN/SMAD1	0.047	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.001	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.012	0.13	-9999	-0.7	11	11
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.21	0.23	-9999	-0.8	14	14
BMP2-4/GREM1	-0.3	0.29	-9999	-0.55	164	164
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.04	0.16	-9999	-0.68	15	15
SMAD1/SMAD6	0.047	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.035	0.17	-9999	-0.65	22	22
BMP6	0.006	0.076	-9999	-0.75	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.075	0.17	-9999	-0.47	31	31
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.047	0.028	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.18	0.25	-9999	-0.56	69	69
CHRD	-0.013	0.14	-9999	-0.79	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.1	0.2	-9999	-0.57	31	31
BMP4	0.003	0.083	-9999	-0.64	5	5
FST	-0.29	0.4	-9999	-0.8	113	113
BMP2-4/NOG	-0.071	0.17	-9999	-0.46	47	47
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.073	0.16	-9999	-0.73	2	2

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.021	0.096	-10000	0	-0.45	14	14
fibroblast growth factor receptor signaling pathway	-0.021	0.096	-10000	0	-0.45	14	14
LAMA1	-0.37	0.41	-10000	0	-0.8	143	143
PRNP	0.011	0.047	-10000	0	-0.8	1	1
GPC1/SLIT2	-0.035	0.13	-10000	0	-0.48	22	22
SMAD2	0.035	0.029	-10000	0	-0.48	1	1
GPC1/PrPc/Cu2+	-0.004	0.043	-10000	0	-0.54	2	2
GPC1/Laminin alpha1	-0.29	0.31	-10000	0	-0.61	143	143
TDGF1	0	0.081	-10000	0	-0.8	3	3
CRIPTO/GPC1	-0.008	0.07	-10000	0	-0.61	4	4
APP/GPC1	-0.002	0.035	-10000	0	-0.61	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.019	0.063	-10000	0	-0.53	4	4
FLT1	0.013	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.002	0.03	-10000	0	-0.53	1	1
SERPINC1	0.007	0.066	-10000	0	-0.8	2	2
FYN	0.017	0.071	-10000	0	-0.53	5	5
FGR	0.017	0.071	-10000	0	-0.53	5	5
positive regulation of MAPKKK cascade	0.001	0.12	-10000	0	-0.44	10	10
SLIT2	-0.033	0.17	-10000	0	-0.65	21	21
GPC1/NRG	-0.12	0.25	-10000	0	-0.61	62	62
NRG1	-0.15	0.32	-10000	0	-0.8	61	61
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.043	-10000	0	-0.53	2	2
LYN	0.019	0.063	-10000	0	-0.53	4	4
mol:Spermine	0.01	0.036	-10000	0	-0.62	1	1
cell growth	-0.021	0.096	-10000	0	-0.45	14	14
BMP signaling pathway	-0.011	0.047	0.8	1	-10000	0	1
SRC	0.019	0.063	-10000	0	-0.53	4	4
TGFBR1	0.013	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.4	0.32	-10000	0	-0.64	193	193
GPC1	0.011	0.047	-10000	0	-0.8	1	1
TGFBR1 (dimer)	0.013	0	-10000	0	-10000	0	0
VEGFA	0.011	0.047	-10000	0	-0.8	1	1
BLK	-0.075	0.21	-10000	0	-0.52	56	56
HCK	0.013	0.093	-10000	0	-0.56	7	7
FGF2	-0.012	0.13	-10000	0	-0.68	11	11
FGFR1	0.008	0.066	-10000	0	-0.8	2	2
VEGFR1 homodimer	0.013	0	-10000	0	-10000	0	0
TGFBR2	0.013	0	-10000	0	-10000	0	0
cell death	-0.002	0.035	-10000	0	-0.61	1	1
ATIII/GPC1	-0.006	0.061	-10000	0	-0.61	3	3
PLA2G2A/GPC1	-0.3	0.23	-10000	0	-0.47	194	194
LCK	0.001	0.12	-10000	0	-0.53	14	14
neuron differentiation	-0.12	0.24	-10000	0	-0.61	62	62
PrPc/Cu2+	-0.002	0.036	-10000	0	-0.62	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.013	0	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.086	0.14	-9999	-0.37	1	1
PDGFB-D/PDGFRB/SLAP	-0.17	0.27	-9999	-0.6	86	86
PDGFB-D/PDGFRB/APS/CBL	-0.15	0.23	-9999	-0.52	86	86
AKT1	-0.047	0.18	-9999	-0.62	2	2
mol:PI-4-5-P2	-0.001	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.061	0.16	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
FGR	-0.11	0.18	-9999	-0.42	1	1
mol:Ca2+	-0.064	0.16	-9999	-0.38	1	1
MYC	-0.023	0.12	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.12	0.19	-9999	-0.42	14	14
LRP1/PDGFRB/PDGFB	-0.16	0.24	-9999	-0.53	89	89
GRB10	0.011	0.047	-9999	-0.8	1	1
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	-0.066	0.16	-9999	-0.39	1	1
PTEN	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
GRB7	0.003	0.089	-9999	-0.76	4	4
PDGFB-D/PDGFRB/SHP2	-0.17	0.27	-9999	-0.6	85	85
PDGFB-D/PDGFRB/GRB10	-0.17	0.27	-9999	-0.6	86	86
cell cycle arrest	-0.17	0.27	-9999	-0.6	86	86
HRAS	0.013	0	-9999	-10000	0	0
HIF1A	-0.031	0.16	-9999	-0.53	2	2
GAB1	-0.066	0.16	-9999	-0.42	2	2
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.059	0.16	-9999	-0.43	1	1
PDGFB-D/PDGFRB	-0.14	0.24	-9999	-0.52	85	85
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.17	0.27	-9999	-0.6	85	85
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.089	0.14	-9999	-0.43	1	1
positive regulation of MAPKKK cascade	-0.17	0.27	-9999	-0.6	85	85
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.066	0.16	-9999	-0.39	1	1
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.18	0.28	-9999	-0.61	87	87
SHB	0.009	0.053	-9999	-0.64	2	2
BLK	-0.17	0.21	-9999	-0.6	21	21
PTPN2	0.012	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.17	0.27	-9999	-0.6	85	85
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	-0.062	0.16	-9999	-0.42	3	3
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.17	0.27	-9999	-0.6	85	85
LCK	-0.12	0.18	-9999	-0.68	2	2
PDGFRB	-0.21	0.36	-9999	-0.8	85	85
ACP1	0.013	0	-9999	-10000	0	0
HCK	-0.11	0.18	-9999	-0.54	2	2
ABL1	-0.076	0.17	-9999	-0.4	12	12
PDGFB-D/PDGFRB/CBL	-0.064	0.16	-9999	-0.41	2	2
PTPN1	0.012	0.003	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	-0.048	0.22	-9999	-0.8	23	23
cell proliferation	-0.02	0.12	-9999	-10000	0	0
SLA	0.011	0.047	-9999	-0.8	1	1
actin cytoskeleton reorganization	-0.1	0.18	-9999	-10000	0	0
SRC	-0.11	0.18	-9999	-0.4	11	11
PI3K	-0.1	0.17	-9999	-0.71	2	2
PDGFB-D/PDGFRB/GRB7/SHC	-0.15	0.24	-9999	-0.53	87	87
SH2B2	0.011	0.047	-9999	-0.8	1	1
PLCgamma1/SPHK1	-0.063	0.16	-9999	-10000	0	0
LYN	-0.11	0.18	-9999	-0.41	2	2
LRP1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.11	0.18	-9999	-10000	0	0
SPHK1	0.002	0.08	-9999	-0.8	3	3
EDG1	-0.001	0.004	-9999	-10000	0	0
mol:DAG	-0.066	0.16	-9999	-0.39	1	1
PLCG1	-0.068	0.16	-9999	-0.4	1	1
NHERF/PDGFRB	-0.15	0.24	-9999	-0.52	86	86
YES1	-0.11	0.18	-9999	-0.39	85	85
cell migration	-0.15	0.24	-9999	-0.52	86	86
SHC/Grb2/SOS1	-0.11	0.18	-9999	-10000	0	0
SLC9A3R2	0.011	0.047	-9999	-0.8	1	1
SLC9A3R1	0.009	0.053	-9999	-0.64	2	2
NHERF1-2/PDGFRB/PTEN	-0.14	0.22	-9999	-0.48	85	85
FYN	-0.11	0.18	-9999	-0.54	2	2
DOK1	-0.1	0.23	-9999	-0.46	85	85
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	-0.003	0.11	-9999	-0.8	6	6
RAC1	-0.045	0.15	-9999	-10000	0	0
PRKCD	-0.1	0.23	-9999	-0.47	85	85
FER	-0.1	0.23	-9999	-0.47	85	85
MAPKKK cascade	-0.11	0.18	-9999	-10000	0	0
RASA1	-0.1	0.23	-9999	-0.47	85	85
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	-0.11	0.2	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.17	0.27	-9999	-0.6	87	87
chemotaxis	-0.074	0.17	-9999	-0.39	12	12
STAT1-3-5/STAT1-3-5	-0.14	0.2	-9999	-0.82	6	6
Bovine Papilomavirus E5/PDGFRB	-0.17	0.28	-9999	-0.61	85	85
PTPRJ	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.25	0.21	-10000	0	-0.91	2	2
IHH	-0.049	0.062	-10000	0	-0.76	1	1
SHH Np/Cholesterol/GAS1	-0.044	0.14	-10000	0	-0.48	28	28
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.044	0.14	0.48	28	-10000	0	28
SMO/beta Arrestin2	-0.13	0.13	-10000	0	-0.53	8	8
SMO	-0.14	0.14	-10000	0	-0.57	8	8
AKT1	-0.051	0.071	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	-0.047	0.19	-10000	0	-0.64	28	28
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.14	0.14	-10000	0	-0.56	8	8
STIL	-0.12	0.15	-10000	0	-0.58	18	18
DHH N/PTCH2	-0.025	0.11	-10000	0	-0.51	15	15
DHH N/PTCH1	-0.13	0.13	-10000	0	-0.57	6	6
PIK3CA	0.013	0	-10000	0	-10000	0	0
DHH	-0.004	0.11	-10000	0	-0.69	7	7
PTHLH	-0.43	0.32	-10000	0	-0.63	214	214
determination of left/right symmetry	-0.14	0.14	-10000	0	-0.56	8	8
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.43	0.32	-10000	0	-0.63	214	214
IHH N/Hhip	-0.057	0.17	-10000	0	-0.67	22	22
DHH N/Hhip	-0.054	0.17	-10000	0	-0.58	28	28
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.14	0.14	-10000	0	-0.56	8	8
pancreas development	-0.045	0.2	-10000	0	-0.79	21	21
HHAT	0.013	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.004	0.084	-10000	0	-0.72	4	4
somite specification	-0.14	0.14	-10000	0	-0.56	8	8
SHH Np/Cholesterol/PTCH1	-0.13	0.16	-10000	0	-0.56	24	24
SHH Np/Cholesterol/PTCH2	-0.049	0.15	-10000	0	-0.49	30	30
SHH Np/Cholesterol/Megalin	-0.061	0.18	-10000	0	-0.54	34	34
SHH	-0.03	0.17	-10000	0	-0.62	24	24
catabolic process	-0.15	0.13	-10000	0	-0.43	1	1
SMO/Vitamin D3	-0.14	0.16	-10000	0	-0.6	17	17
SHH Np/Cholesterol/Hhip	-0.071	0.2	-10000	0	-0.57	38	38
LRP2	-0.026	0.17	-10000	0	-0.8	14	14
receptor-mediated endocytosis	-0.16	0.15	-10000	0	-0.58	20	20
SHH Np/Cholesterol/BOC	-0.072	0.16	-10000	0	-0.43	51	51
SHH Np/Cholesterol/CDO	-0.043	0.14	-10000	0	-0.47	28	28
mesenchymal cell differentiation	0.071	0.2	0.56	38	-10000	0	38
mol:Vitamin D3	-0.13	0.16	-10000	0	-0.56	24	24
IHH N/PTCH2	-0.023	0.098	-10000	0	-0.57	9	9
CDON	0.005	0.075	-10000	0	-0.64	4	4
IHH N/PTCH1	-0.15	0.13	-10000	0	-0.44	1	1
Megalin/LRPAP1	-0.028	0.13	-10000	0	-0.61	14	14
PTCH2	-0.005	0.11	-10000	0	-0.68	8	8
SHH Np/Cholesterol	-0.039	0.13	-10000	0	-0.5	24	24
PTCH1	-0.15	0.13	-10000	0	-0.43	1	1
HHIP	-0.045	0.2	-10000	0	-0.8	21	21

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	-0.17	0.34	-10000	0	-0.8	67	67
EFNB1	-0.021	0.16	-10000	0	-0.62	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.15	0.22	-10000	0	-0.82	10	10
Ephrin B2/EPHB1-2	-0.14	0.22	-10000	0	-0.48	81	81
neuron projection morphogenesis	-0.14	0.21	-10000	0	-0.78	10	10
Ephrin B1/EPHB1-2/Tiam1	-0.15	0.24	-10000	0	-0.49	92	92
DNM1	-0.044	0.21	-10000	0	-0.8	21	21
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.014	0.065	-10000	0	-0.62	3	3
YES1	-0.007	0.086	-10000	0	-0.86	3	3
Ephrin B1/EPHB1-2/NCK2	-0.15	0.24	-10000	0	-0.49	92	92
PI3K	0.014	0.065	-10000	0	-0.63	3	3
mol:GDP	-0.16	0.24	-10000	0	-0.48	92	92
ITGA2B	-0.04	0.2	-10000	0	-0.8	20	20
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.007	0.086	-10000	0	-0.86	3	3
MAP3K7	-0.006	0.066	-10000	0	-0.66	3	3
FGR	-0.007	0.085	-10000	0	-0.85	3	3
TIAM1	0.007	0.065	-10000	0	-0.64	3	3
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.017	0.15	-10000	0	-0.45	31	31
LYN	-0.007	0.086	-10000	0	-0.86	3	3
Ephrin B1/EPHB1-2/Src Family Kinases	-0.01	0.08	-10000	0	-0.8	3	3
Ephrin B1/EPHB1-2	-0.012	0.071	-10000	0	-0.72	3	3
SRC	-0.007	0.085	-10000	0	-0.85	3	3
ITGB3	-0.017	0.15	-10000	0	-0.76	12	12
EPHB1	-0.038	0.19	-10000	0	-0.75	20	20
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.063	0.19	-10000	0	-0.62	31	31
BLK	-0.027	0.095	-10000	0	-0.86	3	3
HCK	-0.008	0.087	-10000	0	-0.86	3	3
regulation of stress fiber formation	0.15	0.24	0.48	92	-10000	0	92
MAPK8	0.02	0.068	-10000	0	-0.58	3	3
Ephrin B1/EPHB1-2/RGS3	-0.15	0.24	-10000	0	-0.49	92	92
endothelial cell migration	-0.001	0.057	-10000	0	-0.56	3	3
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.004	0.076	-10000	0	-0.75	3	3
regulation of focal adhesion formation	0.15	0.24	0.48	92	-10000	0	92
chemotaxis	0.15	0.24	0.48	92	-10000	0	92
PIK3CA	0.013	0	-10000	0	-10000	0	0
Rac1/GTP	-0.14	0.22	-10000	0	-0.81	10	10
angiogenesis	-0.012	0.071	-10000	0	-0.72	3	3
LCK	-0.01	0.086	-10000	0	-0.85	3	3

×

Calcium signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.036	-9999	-10000	0	0
NFATC2	-0.042	0.11	-9999	-0.46	19	19
NFATC3	-0.013	0.036	-9999	-10000	0	0
CD40LG	-0.33	0.36	-9999	-0.88	66	66
PTGS2	-0.34	0.37	-9999	-0.9	67	67
JUNB	0.013	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.016	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.016	0.015	-9999	-10000	0	0
CALM1	0.004	0.011	-9999	-10000	0	0
JUN	0.005	0.011	-9999	-10000	0	0
mol:Ca2+	-0.017	0.014	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.001	0.004	-9999	-10000	0	0
FOSL1	0.005	0.081	-9999	-0.8	3	3
CREM	0.013	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.14	0.15	-9999	-0.66	9	9
FOS	-0.1	0.24	-9999	-0.66	49	49
IFNG	-0.36	0.38	-9999	-0.91	71	71
AP-1/NFAT1-c-4	-0.39	0.37	-9999	-1.1	49	49
FASLG	-0.31	0.34	-9999	-0.87	55	55
NFAT1-c-4/ICER1	-0.085	0.11	-9999	-0.54	8	8
IL2RA	-0.33	0.37	-9999	-0.9	65	65
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.42	-9999	-0.84	142	142
JunB/Fra1/NFAT1-c-4	-0.081	0.11	-9999	-0.53	8	8
IL4	-0.3	0.31	-9999	-0.82	49	49
IL2	-0.012	0.042	-9999	-0.67	1	1
IL3	-0.028	0.023	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	0.005	0.081	-9999	-0.8	3	3
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.002	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.041	0.058	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.1	0.14	-9999	-0.46	20	20
JUN	-0.059	0.16	-9999	-0.47	21	21
HRAS	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.26	-9999	-0.62	56	56
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.005	0.081	-9999	-0.8	3	3
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.26	-9999	-0.61	55	55
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.12	0.21	-9999	-0.52	44	44
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.23	-9999	-0.71	24	24
GRB7	0.003	0.089	-9999	-0.76	4	4
RET51/GFRalpha1/GDNF	-0.17	0.26	-9999	-0.61	55	55
MAPKKK cascade	-0.13	0.19	-9999	-0.64	20	20
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.21	-9999	-0.44	81	81
lamellipodium assembly	-0.093	0.14	-9999	-0.42	20	20
RET51/GFRalpha1/GDNF/SHC	-0.17	0.26	-9999	-0.61	55	55
PIK3CA	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.12	0.21	-9999	-0.44	81	81
RET9/GFRalpha1/GDNF/Shank3	-0.12	0.21	-9999	-0.61	26	26
MAPK3	-0.11	0.24	-9999	-0.72	20	20
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.001	0.1	-9999	-0.72	6	6
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.095	0.22	-9999	-0.66	20	20
DOK5	-0.008	0.12	-9999	-0.7	9	9
GFRA1	-0.12	0.27	-9999	-0.64	64	64
MAPK8	-0.071	0.17	-9999	-0.5	21	21
HRAS/GTP	-0.15	0.22	-9999	-0.74	20	20
tube development	-0.11	0.2	-9999	-0.57	26	26
MAPK1	-0.11	0.24	-9999	-0.72	20	20
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.059	0.16	-9999	-0.54	9	9
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PDLIM7	0.008	0.066	-9999	-0.8	2	2
RET51/GFRalpha1/GDNF/Dok6	-0.17	0.25	-9999	-0.75	25	25
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.26	-9999	-0.61	55	55
RET51/GFRalpha1/GDNF/Dok5	-0.18	0.26	-9999	-0.61	62	62
PRKCA	0.011	0.047	-9999	-0.8	1	1
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.072	0.17	-9999	-0.5	20	20
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.056	0.15	-9999	-0.54	9	9
RET51/GFRalpha1/GDNF/Grb7	-0.18	0.26	-9999	-0.62	59	59
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.079	0.26	-9999	-0.79	35	35
DOK4	0.013	0	-9999	-10000	0	0
JNK cascade	-0.057	0.16	-9999	-0.46	21	21
RET9/GFRalpha1/GDNF/FRS2	-0.12	0.21	-9999	-0.44	84	84
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.056	0.15	-9999	-0.55	9	9
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.085	0.18	-9999	-0.53	21	21
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.082	0.18	-9999	-0.53	20	20
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.085	0.19	-9999	-0.58	20	20
PI3K	-0.095	0.24	-9999	-0.69	20	20
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.11	0.2	-9999	-0.57	26	26
GRB10	0.011	0.047	-9999	-0.8	1	1
activation of MAPKK activity	-0.08	0.18	-9999	-0.52	21	21
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.26	-9999	-0.62	57	57
GAB1	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
IRS2	0.009	0.053	-9999	-0.64	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.085	0.19	-9999	-0.58	20	20
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.26	-9999	-0.61	56	56
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.058	0.23	-9999	-0.8	26	26
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.26	-9999	-0.61	55	55
Rac1/GTP	-0.11	0.16	-9999	-0.52	20	20
RET9/GFRalpha1/GDNF	-0.13	0.23	-9999	-0.49	81	81
GFRalpha1/GDNF	-0.15	0.26	-9999	-0.56	81	81

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.067	0.16	-10000	0	-0.58	22	22
FYN	-0.043	0.24	-10000	0	-0.71	28	28
LAT/GRAP2/SLP76	-0.052	0.2	-10000	0	-0.66	23	23
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.013	0.16	-10000	0	-0.47	25	25
B2M	0.013	0.005	-10000	0	-10000	0	0
IKBKG	-0.02	0.045	-10000	0	-0.18	2	2
MAP3K8	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.047	0.047	-10000	0	-0.12	34	34
integrin-mediated signaling pathway	-0.001	0.023	-10000	0	-0.4	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.039	0.24	-10000	0	-0.68	29	29
TRPV6	-0.33	0.33	-10000	0	-0.65	153	153
CD28	-0.032	0.18	-10000	0	-0.79	17	17
SHC1	-0.045	0.24	-10000	0	-0.71	28	28
receptor internalization	-0.042	0.25	-10000	0	-0.7	31	31
PRF1	-0.059	0.29	-10000	0	-0.87	29	29
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	0	0.13	-10000	0	-0.38	20	20
LAT	-0.051	0.26	-10000	0	-0.78	28	28
EntrezGene:6955	-0.001	0.005	-10000	0	-10000	0	0
CD3D	0.001	0.093	-10000	0	-0.71	5	5
CD3E	-0.007	0.13	-10000	0	-0.77	8	8
CD3G	-0.031	0.18	-10000	0	-0.74	18	18
RASGRP2	0.005	0.024	-10000	0	-0.12	5	5
RASGRP1	-0.008	0.18	-10000	0	-0.5	26	26
HLA-A	0.008	0.06	-10000	0	-0.72	2	2
RASSF5	0.011	0.038	-10000	0	-0.64	1	1
RAP1A/GTP/RAPL	-0.001	0.023	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.058	-10000	0	-0.13	16	16
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.04	0.078	-10000	0	-0.28	10	10
PRKCA	-0.011	0.097	-10000	0	-0.31	15	15
GRAP2	-0.007	0.12	-10000	0	-0.74	8	8
mol:IP3	0.05	0.2	0.24	116	-0.49	17	133
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.039	0.24	-10000	0	-0.65	30	30
ORAI1	0.17	0.17	0.34	153	-10000	0	153
CSK	-0.048	0.25	-10000	0	-0.72	28	28
B7 family/CD28	-0.19	0.29	-10000	0	-0.78	43	43
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.065	0.28	-10000	0	-0.85	28	28
PTPN6	-0.053	0.25	-10000	0	-0.73	28	28
VAV1	-0.048	0.25	-10000	0	-0.72	29	29
Monovalent TCR/CD3	-0.025	0.18	-10000	0	-0.58	23	23
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.052	0.26	-10000	0	-0.76	28	28
PAG1	-0.05	0.25	-10000	0	-0.7	30	30
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.068	0.28	-10000	0	-0.82	29	29
CD80	-0.24	0.38	-10000	0	-0.8	93	93
CD86	0.01	0.047	-10000	0	-0.8	1	1
PDK1/CARD11/BCL10/MALT1	-0.048	0.095	-10000	0	-0.3	21	21
HRAS	0.013	0	-10000	0	-10000	0	0
GO:0035030	-0.11	0.26	-10000	0	-0.62	43	43
CD8A	-0.059	0.23	-10000	0	-0.75	29	29
CD8B	-0.067	0.24	-10000	0	-0.76	32	32
PTPRC	-0.013	0.14	-10000	0	-0.74	10	10
PDK1/PKC theta	-0.015	0.2	-10000	0	-0.6	24	24
CSK/PAG1	-0.044	0.24	-10000	0	-0.71	27	27
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.01	0.047	-10000	0	-0.54	2	2
GRAP2/SLP76	-0.066	0.23	-10000	0	-0.72	25	25
STIM1	0.09	0.086	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.074	-10000	0	-0.19	6	6
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.049	0.28	-10000	0	-0.77	31	31
mol:DAG	-0.009	0.14	-10000	0	-0.44	18	18
RAP1A/GDP	0.012	0.025	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.023	0.17	-10000	0	-0.78	14	14
cytotoxic T cell degranulation	-0.054	0.28	-10000	0	-0.82	29	29
RAP1A/GTP	-0.002	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.025	0.2	-10000	0	-0.56	26	26
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.034	0.24	0.27	74	-0.66	18	92
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.022	0.16	-10000	0	-0.75	14	14
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.046	0.2	-10000	0	-0.65	21	21
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.013	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.094	0.29	-10000	0	-0.78	42	42
CARD11	-0.047	0.21	-10000	0	-0.79	23	23
PRKCB	-0.014	0.11	-10000	0	-0.36	17	17
PRKCE	-0.009	0.096	-10000	0	-0.31	15	15
PRKCQ	-0.029	0.23	-10000	0	-0.69	25	25
LCP2	0.005	0.081	-10000	0	-0.8	3	3
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.007	0.14	-10000	0	-0.39	25	25
IKK complex	0.032	0.054	-10000	0	-0.13	4	4
RAS family/GDP	-0.003	0.008	-10000	0	-10000	0	0
MAP3K14	0.01	0.1	-10000	0	-0.29	16	16
PDPK1	-0.009	0.16	-10000	0	-0.46	22	22
TCR/CD3/MHC I/CD8/Fyn	-0.054	0.28	-10000	0	-0.82	29	29

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.14	0.35	-10000	0	-0.92	50	50
NFATC2	-0.011	0.21	-10000	0	-0.88	11	11
NFATC3	-0.011	0.06	-10000	0	-10000	0	0
CD40LG	-0.36	0.44	-10000	0	-1.1	49	49
ITCH	0.015	0.098	-10000	0	-10000	0	0
CBLB	0.015	0.098	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.33	0.46	-10000	0	-1.2	56	56
JUNB	0.013	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.1	-10000	0	-10000	0	0
T cell anergy	-0.004	0.16	-10000	0	-0.5	6	6
TLE4	0.011	0.17	-10000	0	-0.79	8	8
Jun/NFAT1-c-4/p21SNFT	-0.15	0.24	-10000	0	-1	12	12
AP-1/NFAT1-c-4	-0.38	0.44	-10000	0	-1.2	50	50
IKZF1	-0.001	0.21	-10000	0	-0.89	12	12
T-helper 2 cell differentiation	-0.04	0.21	-10000	0	-0.83	13	13
AP-1/NFAT1	-0.14	0.2	-10000	0	-0.65	24	24
CALM1	0.005	0.063	-10000	0	-10000	0	0
EGR2	-0.048	0.32	-10000	0	-1.4	12	12
EGR3	-0.03	0.25	-10000	0	-1.2	7	7
NFAT1/FOXP3	-0.14	0.36	-10000	0	-0.82	57	57
EGR1	-0.01	0.12	-10000	0	-0.64	11	11
JUN	-0.018	0.035	-10000	0	-10000	0	0
EGR4	-0.08	0.26	-10000	0	-0.79	35	35
mol:Ca2+	-0.01	0.068	-10000	0	-10000	0	0
GBP3	-0.016	0.23	-10000	0	-0.8	20	20
FOSL1	0.005	0.081	-10000	0	-0.8	3	3
NFAT1-c-4/MAF/IRF4	-0.12	0.27	-10000	0	-1.1	11	11
DGKA	0.012	0.16	-10000	0	-0.74	8	8
CREM	0.013	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.22	0.3	-10000	0	-1.1	17	17
CTLA4	-0.16	0.42	-10000	0	-1.1	44	44
NFAT1-c-4 (dimer)/EGR1	-0.097	0.25	-10000	0	-1	12	12
NFAT1-c-4 (dimer)/EGR4	-0.14	0.28	-10000	0	-0.95	18	18
FOS	-0.13	0.24	-10000	0	-0.67	49	49
IFNG	-0.19	0.32	-10000	0	-0.87	37	37
T cell activation	-0.094	0.21	-10000	0	-0.78	9	9
MAF	0.009	0.053	-10000	0	-0.64	2	2
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.025	0.16	0.74	6	-10000	0	6
TNF	-0.11	0.31	-10000	0	-0.98	19	19
FASLG	-0.096	0.37	-10000	0	-1.3	18	18
TBX21	-0.042	0.19	-10000	0	-0.8	17	17
BATF3	0.005	0.081	-10000	0	-0.8	3	3
PRKCQ	-0.001	0.1	-10000	0	-0.72	6	6
PTPN1	0.012	0.16	-10000	0	-0.74	8	8
NFAT1-c-4/ICER1	-0.084	0.23	-10000	0	-0.98	12	12
GATA3	-0.012	0.14	-10000	0	-0.77	10	10
T-helper 1 cell differentiation	-0.18	0.33	-10000	0	-0.83	40	40
IL2RA	-0.3	0.4	-10000	0	-1.1	55	55
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.012	0.16	-10000	0	-0.74	8	8
E2F1	-0.025	0.19	-10000	0	-0.8	17	17
PPARG	-0.24	0.32	-10000	0	-0.64	116	116
SLC3A2	0.012	0.16	-10000	0	-0.74	8	8
IRF4	-0.059	0.23	-10000	0	-0.77	28	28
PTGS2	-0.37	0.46	-10000	0	-1.2	54	54
CSF2	-0.52	0.51	-10000	0	-1.1	109	109
JunB/Fra1/NFAT1-c-4	-0.078	0.22	-10000	0	-1.1	8	8
IL4	-0.043	0.22	-10000	0	-0.88	13	13
IL5	-0.33	0.39	-10000	0	-1	42	42
IL2	-0.096	0.21	-10000	0	-0.79	9	9
IL3	-0.062	0.051	-10000	0	-10000	0	0
RNF128	-0.048	0.26	-10000	0	-0.7	40	40
NFATC1	-0.025	0.16	-10000	0	-0.74	6	6
CDK4	0.008	0.15	0.64	3	-10000	0	3
PTPRK	0.012	0.16	-10000	0	-0.74	8	8
IL8	-0.4	0.47	-10000	0	-1.1	76	76
POU2F1	0.014	0.002	-10000	0	-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	-0.099	0.24	-10000	0	-0.61	37	37
TBX21	-0.13	0.45	-10000	0	-1.2	32	32
B2M	0.011	0.01	-10000	0	-10000	0	0
TYK2	0.018	0.02	-10000	0	-10000	0	0
IL12RB1	-0.068	0.26	-10000	0	-0.82	32	32
GADD45B	-0.047	0.29	-10000	0	-0.79	17	17
IL12RB2	-0.15	0.33	-10000	0	-0.79	63	63
GADD45G	-0.063	0.32	-10000	0	-0.94	17	17
natural killer cell activation	0.008	0.024	-10000	0	-10000	0	0
RELB	0.008	0.066	-10000	0	-0.8	2	2
RELA	0.013	0	-10000	0	-10000	0	0
IL18	-0.005	0.12	-10000	0	-0.64	10	10
IL2RA	-0.086	0.27	-10000	0	-0.8	37	37
IFNG	-0.15	0.32	-10000	0	-0.8	59	59
STAT3 (dimer)	-0.073	0.32	-10000	0	-0.81	30	30
HLA-DRB5	-0.015	0.14	-10000	0	-0.75	11	11
FASLG	-0.13	0.46	-10000	0	-1.2	33	33
NF kappa B2 p52/RelB	-0.19	0.35	-10000	0	-1	35	35
CD4	0.007	0.06	-10000	0	-0.72	2	2
SOCS1	-0.054	0.22	-10000	0	-0.8	25	25
EntrezGene:6955	-0.006	0.017	-10000	0	-10000	0	0
CD3D	-0.002	0.093	-10000	0	-0.71	5	5
CD3E	-0.011	0.13	-10000	0	-0.77	8	8
CD3G	-0.035	0.18	-10000	0	-0.74	18	18
IL12Rbeta2/JAK2	-0.099	0.26	-10000	0	-0.6	63	63
CCL3	-0.12	0.43	-10000	0	-1.2	29	29
CCL4	-0.12	0.43	-10000	0	-1.2	30	30
HLA-A	0.006	0.06	-10000	0	-0.72	2	2
IL18/IL18R	0.03	0.13	-10000	0	-0.53	9	9
NOS2	-0.13	0.43	-10000	0	-1	39	39
IL12/IL12R/TYK2/JAK2/SPHK2	-0.075	0.22	-10000	0	-0.6	29	29
IL1R1	-0.1	0.4	-10000	0	-1.1	29	29
IL4	-0.006	0.024	-10000	0	-10000	0	0
JAK2	0.018	0.02	-10000	0	-10000	0	0
EntrezGene:6957	-0.006	0.016	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.11	0.35	-10000	0	-0.85	42	42
RAB7A	-0.026	0.27	-10000	0	-0.73	10	10
lysosomal transport	-0.022	0.26	-10000	0	-0.69	10	10
FOS	-0.21	0.52	-10000	0	-1.2	56	56
STAT4 (dimer)	-0.071	0.35	-10000	0	-0.91	27	27
STAT5A (dimer)	-0.26	0.41	-10000	0	-1.1	51	51
GZMA	-0.14	0.48	-10000	0	-1.2	38	38
GZMB	-0.15	0.47	-10000	0	-1.2	41	41
HLX	0.008	0.066	-10000	0	-0.8	2	2
LCK	-0.14	0.46	-10000	0	-1.2	35	35
TCR/CD3/MHC II/CD4	-0.044	0.21	-10000	0	-0.69	18	18
IL2/IL2R	-0.086	0.22	-10000	0	-0.57	45	45
MAPK14	-0.048	0.31	-10000	0	-0.81	19	19
CCR5	-0.07	0.35	-10000	0	-1	20	20
IL1B	-0.059	0.24	-10000	0	-0.79	29	29
STAT6	-0.007	0.12	-10000	0	-10000	0	0
STAT4	-0.002	0.11	-10000	0	-0.78	6	6
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	-0.048	0.22	-10000	0	-0.8	23	23
NFKB1	0.013	0	-10000	0	-10000	0	0
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.07	0.26	-10000	0	-0.81	33	33
CD8A	-0.062	0.23	-10000	0	-0.76	29	29
CD8B	-0.071	0.24	-10000	0	-0.77	32	32
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.098	0.24	0.6	37	-10000	0	37
IL2RB	-0.003	0.11	-10000	0	-0.8	6	6
proteasomal ubiquitin-dependent protein catabolic process	-0.06	0.32	-10000	0	-0.82	27	27
IL2RG	-0.016	0.15	-10000	0	-0.79	11	11
IL12	-0.055	0.22	-10000	0	-0.59	43	43
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.026	0.17	-10000	0	-0.78	14	14
IL2	0.002	0.047	-10000	0	-0.8	1	1
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.004	0.12	-10000	0	-0.64	10	10
IL12/IL12R/TYK2/JAK2	-0.15	0.51	-10000	0	-1.2	37	37
MAP2K3	-0.049	0.3	-10000	0	-0.79	20	20
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.059	0.32	-10000	0	-0.82	22	22
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.008	0.053	-10000	0	-0.64	2	2
IL18RAP	-0.002	0.12	-10000	0	-0.71	8	8
IL12Rbeta1/TYK2	-0.041	0.21	-10000	0	-0.63	32	32
EOMES	-0.098	0.27	-10000	0	-0.65	53	53
STAT1 (dimer)	-0.13	0.38	-10000	0	-0.88	42	42
T cell proliferation	-0.018	0.26	0.44	2	-0.65	17	19
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.012	0.062	-10000	0	-0.74	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	-0.72	19	19
ATF2	-0.036	0.29	-10000	0	-0.77	16	16

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.017	0.082	-10000	0	-10000	0	0
epithelial cell differentiation	-0.087	0.14	-10000	0	-0.6	2	2
ITCH	0.028	0.02	-10000	0	-10000	0	0
WWP1	-0.012	0.076	-10000	0	-10000	0	0
FYN	0.011	0.047	-10000	0	-0.8	1	1
EGFR	-0.014	0.15	-10000	0	-0.8	10	10
PRL	-0.003	0.08	-10000	0	-0.8	3	3
neuron projection morphogenesis	-0.046	0.18	-10000	0	-10000	0	0
PTPRZ1	0.003	0.083	-10000	0	-0.64	5	5
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.1	0.17	-10000	0	-0.51	24	24
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.1	0.22	-10000	0	-0.52	60	60
ADAM17	0.028	0.02	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.027	0.098	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.051	0.12	-10000	0	-0.52	7	7
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.12	0.19	-10000	0	-0.56	25	25
GRIN2B	-0.088	0.2	-10000	0	-0.53	25	25
ErbB4/ErbB2/betacellulin	-0.13	0.17	-10000	0	-0.45	37	37
STAT1	-0.048	0.22	-10000	0	-0.8	23	23
HBEGF	0.013	0	-10000	0	-10000	0	0
PRLR	-0.13	0.27	-10000	0	-0.65	64	64
E4ICDs/ETO2	-0.017	0.082	-10000	0	-10000	0	0
axon guidance	-0.026	0.091	-10000	0	-0.41	2	2
NEDD4	0.028	0.02	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.11	0.21	-10000	0	-0.49	66	66
CBFA2T3	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	-0.028	0.053	-10000	0	-0.5	2	2
MAPK3	-0.056	0.18	-10000	0	-10000	0	0
STAT1 (dimer)	-0.056	0.16	-10000	0	-0.56	22	22
MAPK1	-0.056	0.18	-10000	0	-10000	0	0
JAK2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.11	0.2	-10000	0	-0.49	62	62
NRG1	-0.096	0.26	-10000	0	-0.61	61	61
NRG3	-0.029	0.15	-10000	0	-0.64	17	17
NRG2	-0.38	0.32	-10000	0	-0.64	184	184
NRG4	-0.07	0.22	-10000	0	-0.64	38	38
heart development	-0.026	0.091	-10000	0	-0.41	2	2
neural crest cell migration	-0.11	0.2	-10000	0	-0.48	62	62
ERBB2	0.03	0.054	-10000	0	-0.62	2	2
WWOX/E4ICDs	-0.017	0.082	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.097	0.16	-10000	0	-0.49	31	31
apoptosis	0.091	0.14	0.66	10	-10000	0	10
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.26	0.21	-10000	0	-0.52	66	66
ErbB4/ErbB2/epiregulin	-0.12	0.16	-10000	0	-0.46	30	30
ErbB4/ErbB4/betacellulin/betacellulin	-0.14	0.2	-10000	0	-0.52	36	36
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.1	0.15	-10000	0	-0.65	3	3
MDM2	-0.013	0.084	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.11	0.19	-10000	0	-0.49	59	59
STAT5A	-0.016	0.086	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.13	0.21	-10000	0	-0.5	68	68
DLG4	0.011	0.038	-10000	0	-0.64	1	1
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.04	0.058	-10000	0	-10000	0	0
STAT5A (dimer)	-0.092	0.14	-10000	0	-0.66	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.017	0.085	-10000	0	-10000	0	0
LRIG1	0	0.091	-10000	0	-0.64	6	6
EREG	-0.17	0.3	-10000	0	-0.64	84	84
BTC	-0.19	0.3	-10000	0	-0.64	94	94
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.026	0.092	-10000	0	-0.42	2	2
ERBB4	-0.027	0.098	-10000	0	-10000	0	0
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.02	0.053	-10000	0	-0.37	6	6
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.071	0.13	-10000	0	-0.44	23	23
glial cell differentiation	0.04	0.057	-10000	0	-10000	0	0
WWOX	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.17	0.25	-10000	0	-0.66	37	37

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0.047	-10000	0	-0.8	1	1
RAS family/GTP/Tiam1	-0.092	0.11	-10000	0	-0.46	2	2
NT3 (dimer)/TRKC	-0.25	0.3	-10000	0	-0.56	133	133
NT3 (dimer)/TRKB	-0.25	0.3	-10000	0	-0.72	60	60
SHC/Grb2/SOS1/GAB1/PI3K	0.04	0	-10000	0	-10000	0	0
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.042	0.2	-10000	0	-0.72	23	23
PIK3CA	0.013	0	-10000	0	-10000	0	0
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.062	0.24	-10000	0	-0.8	28	28
NTRK2	-0.17	0.31	-10000	0	-0.68	80	80
NTRK3	-0.14	0.28	-10000	0	-0.64	73	73
NT-4/5 (dimer)/TRKB	-0.14	0.22	-10000	0	-0.59	27	27
neuron apoptosis	0.12	0.13	0.46	10	-10000	0	10
SHC 2-3/Grb2	-0.12	0.14	-10000	0	-0.51	10	10
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.11	0.13	-10000	0	-0.4	31	31
SHC3	-0.12	0.14	-10000	0	-0.41	36	36
STAT3 (dimer)	0.014	0.054	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.19	0.25	-10000	0	-0.47	121	121
RIN/GDP	-0.053	0.11	-10000	0	-0.29	2	2
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.088	0.13	0.26	1	-0.4	13	14
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.014	0.12	-10000	0	-0.8	7	7
MAGED1	0.011	0.038	-10000	0	-0.64	1	1
PTPN11	0.013	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.013	0.001	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.18	0.27	-10000	0	-0.57	92	92
TRKA/NEDD4-2	-0.057	0.18	-10000	0	-0.61	28	28
ELMO1	0.013	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.16	0.34	-10000	0	-0.8	66	66
HRAS	0.013	0	-10000	0	-10000	0	0
DOCK1	0.013	0	-10000	0	-10000	0	0
GAB2	0.009	0.053	-10000	0	-0.64	2	2
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.005	0.081	-10000	0	-0.8	3	3
DNM1	-0.043	0.21	-10000	0	-0.8	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.085	0.13	0.25	1	-0.46	6	7
mol:GDP	-0.079	0.15	-10000	0	-0.42	9	9
NGF (dimer)	-0.16	0.33	-10000	0	-0.8	66	66
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.047	0.11	-10000	0	-0.29	2	2
TIAM1	0.007	0.065	-10000	0	-0.64	3	3
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.15	0.22	-10000	0	-0.57	31	31
KIDINS220/CRKL/C3G	-0.002	0.035	-10000	0	-0.61	1	1
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.005	0.052	-10000	0	-0.53	3	3
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.18	0.3	-10000	0	-0.64	90	90
RAP1/GDP	-0.06	0.072	-10000	0	-0.37	1	1
KIDINS220/CRKL	0.011	0.047	-10000	0	-0.8	1	1
BDNF (dimer)	-0.042	0.2	-10000	0	-0.72	23	23
ubiquitin-dependent protein catabolic process	-0.16	0.26	-10000	0	-0.56	88	88
Schwann cell development	-0.051	0.038	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.005	0.047	-10000	0	-0.48	3	3
FRS2 family/SHP2/CRK family/C3G/GAB2	0.039	0.035	-10000	0	-10000	0	0
RAP1B	0.011	0.047	-10000	0	-0.8	1	1
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.28	0.3	-10000	0	-0.7	85	85
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.05	0.077	-10000	0	-0.57	1	1
STAT3	0.014	0.054	-10000	0	-10000	0	0
axon guidance	-0.26	0.28	-10000	0	-0.66	85	85
MAPK3	-0.13	0.26	-10000	0	-0.52	92	92
MAPK1	-0.13	0.26	-10000	0	-0.52	92	92
CDC42/GDP	-0.047	0.11	-10000	0	-0.29	2	2
NTF3	-0.18	0.3	-10000	0	-0.64	90	90
NTF4	0.013	0.001	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	-0.16	0.26	-10000	0	-0.56	88	88
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.19	0.23	0.26	1	-0.52	77	78
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.21	0.3	-10000	0	-0.51	135	135
RGS19	0.013	0	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.007	0.087	-10000	0	-10000	0	0
Rac1/GDP	-0.047	0.11	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	-0.16	0.27	-10000	0	-0.57	88	88
neuron projection morphogenesis	-0.051	0.13	-10000	0	-0.54	1	1
NGF (dimer)/TRKA/NEDD4-2	-0.16	0.26	-10000	0	-0.56	88	88
MAP2K1	0.043	0	-10000	0	-10000	0	0
NGFR	-0.023	0.16	-10000	0	-0.73	15	15
NGF (dimer)/TRKA/GIPC/GAIP	-0.07	0.16	-10000	0	-0.55	9	9
RAS family/GTP/PI3K	0.034	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.004	0.044	-10000	0	-0.45	3	3
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.038	-10000	0	-0.64	1	1
MAPKKK cascade	-0.09	0.14	-10000	0	-0.48	8	8
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.057	0.18	-10000	0	-0.61	28	28
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.2	-10000	0	-0.52	31	31
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.14	0.22	-10000	0	-0.48	86	86
MATK	-0.008	0.13	-10000	0	-0.8	8	8
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.056	0.067	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.095	0.14	0.28	1	-0.39	21	22
Rac1/GTP	-0.13	0.13	-10000	0	-0.38	34	34
FRS2 family/SHP2/CRK family	-0.006	0.051	-10000	0	-0.45	4	4

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.001	0.046	-9999	-0.64	1	1
SVIL	0.002	0.024	-9999	-10000	0	0
ZNF318	0.04	0.064	-9999	-10000	0	0
JMJD2C	0.006	0.027	-9999	-0.12	11	11
T-DHT/AR/Ubc9	-0.1	0.18	-9999	-0.46	57	57
CARM1	0.012	0.004	-9999	-10000	0	0
PRDX1	0.015	0.004	-9999	-10000	0	0
PELP1	0.018	0.01	-9999	-10000	0	0
CTNNB1	0.003	0.042	-9999	-0.64	1	1
AKT1	0.022	0.018	-9999	-10000	0	0
PTK2B	0.006	0.016	-9999	-10000	0	0
MED1	0.02	0.051	-9999	-0.8	1	1
MAK	0.028	0.11	-9999	-0.67	5	5
response to oxidative stress	0.002	0.005	-9999	-10000	0	0
HIP1	0.002	0.024	-9999	-10000	0	0
GSN	0.001	0.027	-9999	-10000	0	0
NCOA2	0.003	0.075	-9999	-0.64	4	4
NCOA6	0.003	0.023	-9999	-10000	0	0
DNA-PK	0.033	0.068	-9999	-10000	0	0
NCOA4	0.011	0.005	-9999	-10000	0	0
PIAS3	0.005	0.019	-9999	-10000	0	0
cell proliferation	-0.011	0.12	-9999	-0.77	5	5
XRCC5	0.02	0.014	-9999	-10000	0	0
UBE3A	-0.004	0.039	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.11	0.2	-9999	-0.48	63	63
FHL2	-0.024	0.12	-9999	-1	2	2
RANBP9	0.003	0.023	-9999	-10000	0	0
JMJD1A	-0.06	0.077	-9999	-0.14	147	147
CDK6	0.001	0.1	-9999	-0.8	5	5
TGFB1I1	-0.019	0.13	-9999	-0.81	8	8
T-DHT/AR/CyclinD1	-0.12	0.2	-9999	-0.49	61	61
XRCC6	0.02	0.014	-9999	-10000	0	0
T-DHT/AR	-0.12	0.21	-9999	-0.5	57	57
CTDSP1	0.011	0.005	-9999	-10000	0	0
CTDSP2	0.033	0.043	-9999	-10000	0	0
BRCA1	0.002	0.024	-9999	-10000	0	0
TCF4	0.028	0.031	-9999	-10000	0	0
CDKN2A	-0.3	0.39	-9999	-0.76	124	124
SRF	0.03	0.024	-9999	-10000	0	0
NKX3-1	-0.13	0.14	-9999	-0.82	2	2
KLK3	-0.25	0.57	-9999	-1.4	57	57
TMF1	0.011	0.005	-9999	-10000	0	0
HNRNPA1	0.025	0.026	-9999	-10000	0	0
AOF2	-0.013	0.028	-9999	-0.071	55	55
APPL1	0.042	0.038	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.094	0.18	-9999	-0.46	57	57
AR	-0.14	0.27	-9999	-0.68	57	57
UBA3	0.011	0.005	-9999	-10000	0	0
PATZ1	0.025	0.026	-9999	-10000	0	0
PAWR	0.011	0.005	-9999	-10000	0	0
PRKDC	0.02	0.014	-9999	-10000	0	0
PA2G4	0.026	0.029	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.081	0.17	-9999	-0.42	57	57
RPS6KA3	0.001	0.027	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.1	0.18	-9999	-0.46	57	57
LATS2	0.024	0.023	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.077	0.17	-9999	-0.42	57	57
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.041	0.17	-9999	-0.65	21	21
KLK2	-0.08	0.19	-9999	-0.97	11	11
CASP8	0.017	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.093	0.18	-9999	-0.44	57	57
TMPRSS2	-0.52	0.52	-9999	-1.1	145	145
CCND1	-0.007	0.11	-9999	-0.72	7	7
PIAS1	-0.004	0.039	-9999	-10000	0	0
mol:T-DHT	-0.026	0.037	-9999	-0.069	116	116
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.014	0.059	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.11	0.19	-9999	-0.47	61	61
CMTM2	-0.014	0.15	-9999	-0.8	11	11
SNURF	-0.007	0.11	-9999	-0.64	9	9
ZMIZ1	-0.007	0.031	-9999	-10000	0	0
CCND3	0.014	0.002	-9999	-10000	0	0
TGIF1	0.025	0.026	-9999	-10000	0	0
FKBP4	0.003	0.023	-9999	-10000	0	0

×

Thromboxane A2 receptor 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
TGM2	-0.049	0.21	-10000	0	-0.8	22	22
GNB1/GNG2	-0.057	0.077	-10000	0	-0.21	20	20
AKT1	-0.002	0.12	-10000	0	-0.24	2	2
EGF	-0.14	0.27	-10000	0	-0.64	69	69
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.018	0.1	-10000	0	-0.51	4	4
mol:Ca2+	-0.029	0.16	-10000	0	-0.3	59	59
LYN	-0.016	0.1	-10000	0	-0.51	4	4
RhoA/GTP	-0.034	0.051	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.033	0.18	-10000	0	-0.34	59	59
GNG2	0.011	0.047	-10000	0	-0.8	1	1
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.007	0.067	-10000	0	-10000	0	0
G beta5/gamma2	-0.074	0.1	-10000	0	-0.29	21	21
PRKCH	-0.038	0.18	-10000	0	-0.35	54	54
DNM1	-0.043	0.21	-10000	0	-0.8	21	21
TXA2/TP beta/beta Arrestin3	-0.023	0.065	-10000	0	-0.32	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.006	0.076	-10000	0	-0.75	3	3
G12 family/GTP	-0.084	0.12	-10000	0	-0.3	60	60
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.011	0.047	-10000	0	-0.8	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.12	0.36	14	-10000	0	14
mol:NADP	0	0.1	-10000	0	-0.8	5	5
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.008	0.12	-10000	0	-0.71	9	9
mol:IP3	-0.045	0.2	-10000	0	-0.37	60	60
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.074	0.26	-10000	0	-0.51	61	61
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.079	0.17	-10000	0	-0.57	13	13
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.021	0.11	-10000	0	-0.51	4	4
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	-0.008	0.13	-10000	0	-0.8	8	8
PRKCB1	-0.046	0.2	-10000	0	-0.37	59	59
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0	0.1	-10000	0	-0.8	5	5
TXA2/TXA2-R family	-0.075	0.26	-10000	0	-0.52	64	64
LCK	-0.029	0.12	-10000	0	-0.53	6	6
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.038	0.13	-10000	0	-0.71	4	4
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.046	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.037	0.12	-10000	0	-0.71	4	4
MAPK14	-0.008	0.13	-10000	0	-0.25	5	5
TGM2/GTP	-0.058	0.22	-10000	0	-0.48	29	29
MAPK11	-0.008	0.13	-10000	0	-0.25	5	5
ARHGEF1	-0.007	0.1	-10000	0	-0.22	2	2
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.045	0.2	-10000	0	-0.38	64	64
RAB11/GDP	0.013	0.002	-10000	0	-10000	0	0
ICAM1	-0.03	0.16	-10000	0	-0.3	62	62
cAMP biosynthetic process	-0.044	0.19	-10000	0	-0.37	35	35
Gq family/GTP/EBP50	-0.008	0.088	-10000	0	-0.46	1	1
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.016	0.1	-10000	0	-0.51	4	4
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.013	0.12	-10000	0	-0.36	5	5
VCAM1	-0.04	0.18	-10000	0	-0.33	73	73
TP beta/Gq family/GDP/G beta5/gamma2	0.007	0.067	-10000	0	-10000	0	0
platelet activation	-0.014	0.17	-10000	0	-0.32	23	23
PGI2/IP	-0.016	0.1	-10000	0	-0.62	8	8
PRKACA	0.009	0.067	-10000	0	-0.34	10	10
Gq family/GDP/G beta5/gamma2	0.011	0.067	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2	-0.028	0.09	-10000	0	-0.35	21	21
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.015	0.15	-10000	0	-0.52	22	22
mol:DAG	-0.054	0.22	-10000	0	-0.42	59	59
EGFR	-0.014	0.15	-10000	0	-0.8	10	10
TXA2/TP alpha	-0.066	0.24	-10000	0	-0.51	36	36
Gq family/GTP	-0.038	0.094	-10000	0	-0.25	49	49
YES1	-0.016	0.1	-10000	0	-0.51	4	4
GNAI2/GTP	-0.035	0.11	-10000	0	-0.62	4	4
PGD2/DP	-0.006	0.057	-10000	0	-0.57	3	3
SLC9A3R1	0.009	0.053	-10000	0	-0.64	2	2
FYN	-0.017	0.11	-10000	0	-0.54	5	5
mol:NO	0	0.1	-10000	0	-0.8	5	5
GNA15	0.013	0	-10000	0	-10000	0	0
PGK/cGMP	-0.023	0.1	-10000	0	-0.49	14	14
RhoA/GDP	0.013	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.067	0.18	-10000	0	-0.79	9	9
NOS3	0	0.1	-10000	0	-0.8	5	5
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.039	0.18	-10000	0	-0.35	54	54
PRKCB	-0.044	0.19	-10000	0	-0.36	60	60
PRKCE	-0.037	0.19	-10000	0	-0.36	53	53
PRKCD	-0.043	0.2	-10000	0	-0.38	56	56
PRKCG	-0.064	0.22	-10000	0	-0.43	64	64
muscle contraction	-0.063	0.25	-10000	0	-0.48	64	64
PRKCZ	-0.032	0.18	-10000	0	-0.36	25	25
ARR3	0.001	0.004	-10000	0	-10000	0	0
TXA2/TP beta	-0.039	0.13	-10000	0	-0.53	10	10
PRKCQ	-0.043	0.19	-10000	0	-0.37	58	58
MAPKKK cascade	-0.059	0.23	-10000	0	-0.44	61	61
SELE	-0.045	0.19	-10000	0	-0.38	61	61
TP beta/GNAI2/GDP/G beta/gamma	-0.038	0.12	-10000	0	-0.7	4	4
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.095	0.24	-10000	0	-0.64	50	50
chemotaxis	-0.09	0.3	-10000	0	-0.6	64	64
GNA12	0.008	0.066	-10000	0	-0.8	2	2
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	0.013	0	-10000	0	-10000	0	0
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.071	0.15	-10000	0	-0.37	58	58
regulation of S phase of mitotic cell cycle	-0.025	0.12	-10000	0	-0.28	11	11
GNAO1	0.008	0.06	-10000	0	-0.72	2	2
HRAS	0.013	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.029	0.14	-10000	0	-0.5	2	2
T-DHT/AR	-0.092	0.19	-10000	0	-0.49	57	57
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	49	49
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.011	0.038	-10000	0	-0.64	1	1
mol:GDP	-0.09	0.19	-10000	0	-0.48	57	57
cell proliferation	-0.046	0.2	-10000	0	-0.61	13	13
PIK3CA	0.013	0	-10000	0	-10000	0	0
FOS	-0.1	0.33	-10000	0	-0.84	49	49
mol:Ca2+	-0.011	0.02	-10000	0	-0.092	4	4
MAPK3	-0.036	0.17	-10000	0	-0.53	13	13
MAPK1	-0.016	0.099	-10000	0	-0.28	13	13
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.005	49	49
cAMP biosynthetic process	0.01	0.02	-10000	0	-10000	0	0
GNG2	0.011	0.047	-10000	0	-0.8	1	1
potassium channel inhibitor activity	0	0.002	-10000	0	-0.005	49	49
HRAS/GTP	-0.066	0.13	-10000	0	-0.4	15	15
actin cytoskeleton reorganization	0	0	-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	-0.005	49	49
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.044	0.19	0.42	49	-10000	0	49
T-DHT/AR/PELP1	-0.077	0.16	-10000	0	-0.42	57	57
HRAS/GDP	-0.083	0.18	-10000	0	-0.45	57	57
CREB1	-0.049	0.2	-10000	0	-0.46	49	49
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.11	0.26	-10000	0	-0.65	57	57
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.034	0.14	-10000	0	-0.5	2	2
RAC1-CDC42/GDP	-0.08	0.17	-10000	0	-0.43	55	55
T-DHT/AR/PELP1/Src	-0.07	0.15	-10000	0	-0.37	57	57
MAP2K2	-0.029	0.14	-10000	0	-0.5	2	2
T-DHT/AR/PELP1/Src/PI3K	-0.025	0.12	-10000	0	-0.28	11	11
GNAZ	-0.004	0.11	-10000	0	-0.73	7	7
SHBG	0.013	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.022	0.066	-10000	0	-0.44	1	1
mol:T-DHT	0	0.001	-10000	0	-0.003	36	36
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	-0.004	0.099	-10000	0	-0.61	8	8
Gi family/GTP	-0.035	0.076	-10000	0	-0.4	4	4
CDC42	0.013	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.037	0.16	-10000	0	-0.45	18	18
IKBKB	-0.015	0.082	-10000	0	-0.28	2	2
AKT1	-0.035	0.12	-10000	0	-0.29	29	29
IKBKG	-0.014	0.086	-10000	0	-0.29	4	4
CALM1	-0.052	0.13	-10000	0	-0.41	22	22
PIK3CA	0.013	0	-10000	0	-10000	0	0
MAP3K1	-0.069	0.22	-10000	0	-0.65	21	21
MAP3K7	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.064	0.13	-10000	0	-0.44	22	22
DOK1	0.013	0	-10000	0	-10000	0	0
AP-1	-0.033	0.1	-10000	0	-0.27	8	8
LYN	0.013	0	-10000	0	-10000	0	0
BLNK	-0.056	0.2	-10000	0	-0.64	32	32
SHC1	0.013	0	-10000	0	-10000	0	0
BCR complex	-0.16	0.31	-10000	0	-0.67	71	71
CD22	-0.14	0.29	-10000	0	-0.85	35	35
CAMK2G	-0.041	0.12	-10000	0	-0.38	22	22
CSNK2A1	0.013	0	-10000	0	-10000	0	0
INPP5D	0.011	0.038	-10000	0	-0.64	1	1
SHC/GRB2/SOS1	-0.13	0.22	-10000	0	-0.72	22	22
GO:0007205	-0.064	0.14	-10000	0	-0.45	22	22
SYK	0.011	0.038	-10000	0	-0.64	1	1
ELK1	-0.055	0.13	-10000	0	-0.42	23	23
NFATC1	-0.082	0.21	-10000	0	-0.48	50	50
B-cell antigen/BCR complex	-0.16	0.31	-10000	0	-0.67	71	71
PAG1/CSK	-0.004	0.05	-10000	0	-0.61	2	2
NFKBIB	0.006	0.031	0.083	1	-10000	0	1
HRAS	-0.058	0.14	-10000	0	-0.46	22	22
NFKBIA	0.006	0.031	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.012	0.026	-10000	0	-10000	0	0
RasGAP/Csk	-0.12	0.24	-10000	0	-0.58	53	53
mol:GDP	-0.062	0.13	-10000	0	-0.42	22	22
PTEN	0.013	0	-10000	0	-10000	0	0
CD79B	-0.029	0.18	-10000	0	-0.78	16	16
NF-kappa-B/RelA/I kappa B alpha	0.013	0.025	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.11	0.24	-10000	0	-0.55	55	55
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.073	0.13	-10000	0	-0.45	22	22
CSK	0.013	0	-10000	0	-10000	0	0
FOS	-0.095	0.18	-10000	0	-0.5	25	25
CHUK	-0.014	0.086	-10000	0	-0.29	4	4
IBTK	0.013	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.08	0.14	-10000	0	-0.55	11	11
PTPN6	-0.13	0.27	-10000	0	-0.8	34	34
RELA	0.013	0	-10000	0	-10000	0	0
BCL2A1	0.007	0.038	-10000	0	-0.12	18	18
VAV2	-0.17	0.29	-10000	0	-0.76	51	51
ubiquitin-dependent protein catabolic process	0.01	0.03	0.086	1	-10000	0	1
BTK	-0.004	0.03	0.38	1	-10000	0	1
CD19	-0.17	0.33	-10000	0	-0.8	56	56
MAP4K1	-0.012	0.14	-10000	0	-0.75	10	10
CD72	-0.083	0.26	-10000	0	-0.8	36	36
PAG1	0.008	0.066	-10000	0	-0.8	2	2
MAPK14	-0.048	0.19	-10000	0	-0.53	21	21
SH3BP5	0.011	0.038	-10000	0	-0.64	1	1
PIK3AP1	-0.073	0.16	-10000	0	-0.47	33	33
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.099	0.22	-10000	0	-0.55	39	39
RAF1	-0.047	0.14	-10000	0	-0.42	22	22
RasGAP/p62DOK/SHIP	-0.12	0.23	-10000	0	-0.81	19	19
CD79A	-0.16	0.32	-10000	0	-0.75	70	70
re-entry into mitotic cell cycle	-0.034	0.1	-10000	0	-0.27	8	8
RASA1	0.013	0	-10000	0	-10000	0	0
MAPK3	-0.024	0.12	-10000	0	-0.45	2	2
MAPK1	-0.024	0.12	-10000	0	-0.51	1	1
CD72/SHP1	-0.12	0.32	-10000	0	-0.89	33	33
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.05	0.19	-10000	0	-0.54	20	20
actin cytoskeleton organization	-0.11	0.26	-10000	0	-0.62	50	50
NF-kappa-B/RelA	0.031	0.048	-10000	0	-10000	0	0
Calcineurin	-0.053	0.095	-10000	0	-0.47	2	2
PI3K	-0.14	0.23	-10000	0	-0.62	50	50
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.077	0.14	0.25	1	-0.48	22	23
SOS1	0.013	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.067	0.23	-10000	0	-0.76	22	22
DAPP1	-0.094	0.21	-10000	0	-0.73	21	21
cytokine secretion	-0.075	0.19	-10000	0	-0.45	50	50
mol:DAG	-0.073	0.13	-10000	0	-0.45	22	22
PLCG2	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.035	0.13	-10000	0	-0.48	3	3
B-cell antigen/BCR complex/FcgammaRIIB	-0.14	0.28	-10000	0	-0.6	73	73
mol:PI-3-4-5-P3	-0.099	0.16	-10000	0	-0.41	48	48
ETS1	-0.033	0.12	-10000	0	-0.43	4	4
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.15	0.25	-10000	0	-0.59	57	57
B-cell antigen/BCR complex/LYN	-0.1	0.22	-10000	0	-0.78	19	19
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.013	0	-10000	0	-10000	0	0
RAC1	-0.12	0.28	-10000	0	-0.68	50	50
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.29	-10000	0	-0.9	30	30
CARD11	-0.086	0.18	-10000	0	-0.48	41	41
FCGR2B	0	0.091	-10000	0	-0.64	6	6
PPP3CA	0.013	0	-10000	0	-10000	0	0
BCL10	0.013	0	-10000	0	-10000	0	0
IKK complex	0.004	0.04	-10000	0	-10000	0	0
PTPRC	-0.011	0.14	-10000	0	-0.74	10	10
PDPK1	-0.034	0.12	-10000	0	-0.29	28	28
PPP3CB	0.013	0	-10000	0	-10000	0	0
PPP3CC	0.013	0	-10000	0	-10000	0	0
POU2F2	0.006	0.044	-10000	0	-0.14	24	24

×

Caspase cascade in apoptosis

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
TOP1	-0.038	0.18	-10000	0	-0.42	49	49
ACTA1	-0.14	0.24	-10000	0	-0.62	52	52
NUMA1	-0.039	0.18	-10000	0	-0.42	49	49
SPTAN1	-0.063	0.24	-10000	0	-0.56	49	49
LIMK1	-0.063	0.24	-10000	0	-0.57	46	46
BIRC3	-0.024	0.17	-10000	0	-0.8	14	14
BIRC2	-0.003	0.11	-10000	0	-0.8	6	6
BAX	0.013	0	-10000	0	-10000	0	0
CASP10	-0.097	0.3	-10000	0	-0.72	52	52
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	-0.038	0.18	-10000	0	-0.42	49	49
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.061	0.23	-10000	0	-0.55	49	49
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	-0.063	0.24	-10000	0	-0.56	49	49
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.001	0.1	-10000	0	-0.6	5	5
BID	-0.027	0.12	-10000	0	-0.29	50	50
MAP3K1	-0.011	0.075	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.063	0.24	-10000	0	-0.56	49	49
CASP9	0.013	0.002	-10000	0	-10000	0	0
DNA repair	0.006	0.063	-10000	0	-0.2	6	6
neuron apoptosis	0.018	0.024	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.053	0.23	-10000	0	-0.72	23	23
APAF1	0.013	0	-10000	0	-10000	0	0
CASP6	-0.002	0.1	-10000	0	-0.47	1	1
TRAF2	0.008	0.066	-10000	0	-0.8	2	2
ICAD/CAD	-0.053	0.23	-10000	0	-0.74	22	22
CASP7	0.007	0.065	0.31	10	-10000	0	10
KRT18	0.004	0.065	-10000	0	-0.48	4	4
apoptosis	-0.042	0.21	-10000	0	-0.65	23	23
DFFA	-0.063	0.24	-10000	0	-0.56	49	49
DFFB	-0.063	0.24	-10000	0	-0.56	49	49
PARP1	-0.006	0.063	0.2	6	-10000	0	6
actin filament polymerization	0.049	0.22	0.69	22	-10000	0	22
TNF	-0.025	0.17	-10000	0	-0.76	15	15
CYCS	-0.017	0.094	-10000	0	-0.26	25	25
SATB1	-0.006	0.12	-10000	0	-0.47	3	3
SLK	-0.063	0.24	-10000	0	-0.56	49	49
p15 BID/BAX	-0.018	0.11	-10000	0	-0.32	22	22
CASP2	0.034	0.071	-10000	0	-0.36	1	1
JNK cascade	0.011	0.075	-10000	0	-10000	0	0
CASP3	-0.075	0.25	-10000	0	-0.6	49	49
LMNB2	0.028	0.06	-10000	0	-0.37	1	1
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.011	0.038	-10000	0	-0.64	1	1
Mammalian IAPs/DIABLO	-0.031	0.14	-10000	0	-0.59	16	16
negative regulation of DNA binding	-0.001	0.099	-10000	0	-0.6	5	5
stress fiber formation	-0.061	0.23	-10000	0	-0.55	49	49
GZMB	-0.12	0.34	-10000	0	-0.82	52	52
CASP1	0.016	0.032	-10000	0	-0.37	2	2
LMNB1	0.028	0.06	-10000	0	-0.37	1	1
APP	0.018	0.024	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	-0.045	0.2	-10000	0	-0.62	24	24
LMNA	0.028	0.06	-10000	0	-0.37	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.027	0.075	-10000	0	-0.37	4	4
LRDD	0.011	0.047	-10000	0	-0.8	1	1
SREBF1	-0.063	0.24	-10000	0	-0.56	49	49
APAF-1/Caspase 9	-0.001	0.075	0.48	5	-10000	0	5
nuclear fragmentation during apoptosis	-0.038	0.18	-10000	0	-0.41	49	49
CFL2	-0.051	0.22	-10000	0	-0.72	22	22
GAS2	-0.12	0.26	-10000	0	-0.62	48	48
positive regulation of apoptosis	0.032	0.06	-10000	0	-0.37	1	1
PRF1	-0.051	0.22	-10000	0	-0.8	24	24

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.022	0	-9999	-10000	0	0
ADCY5	-0.072	0.18	-9999	-0.42	65	65
ADCY6	0.009	0.072	-9999	-0.4	9	9
ADCY7	0.022	0	-9999	-10000	0	0
ADCY1	-0.002	0.11	-9999	-0.54	13	13
ADCY2	-0.11	0.2	-9999	-0.41	95	95
ADCY3	0.022	0	-9999	-10000	0	0
ADCY8	-0.002	0.094	-9999	-0.54	9	9
PRKCE	0.012	0	-9999	-10000	0	0
ADCY9	0.022	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.048	0.11	-9999	-0.43	5	5

×

Glucocorticoid receptor regulatory network

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
PCK2	0.013	0.061	-10000	0	-10000	0	0
SMARCC2	0.015	0.003	-10000	0	-10000	0	0
SMARCC1	0.015	0.003	-10000	0	-10000	0	0
TBX21	-0.089	0.23	-10000	0	-0.84	21	21
SUMO2	0.014	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	-0.039	0.21	-10000	0	-0.78	23	23
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.009	0.053	-10000	0	-0.64	2	2
GR alpha/HSP90/FKBP51/HSP90	0.091	0.095	0.38	4	-10000	0	4
PRL	-0.089	0.17	-10000	0	-0.76	6	6
cortisol/GR alpha (dimer)/TIF2	0.2	0.22	0.6	32	-10000	0	32
RELA	-0.007	0.089	-10000	0	-10000	0	0
FGG	0.12	0.24	0.57	12	-0.66	15	27
GR beta/TIF2	0.09	0.11	0.41	6	-0.44	1	7
IFNG	-0.35	0.31	-10000	0	-0.87	67	67
apoptosis	0.025	0.16	0.47	6	-0.71	1	7
CREB1	0.017	0.019	-10000	0	-10000	0	0
histone acetylation	0.006	0.12	0.45	3	-0.39	5	8
BGLAP	-0.039	0.11	-10000	0	-0.56	1	1
GR/PKAc	0.09	0.09	0.36	4	-10000	0	4
NF kappa B1 p50/RelA	-0.019	0.16	-10000	0	-0.45	7	7
SMARCD1	0.015	0.003	-10000	0	-10000	0	0
MDM2	0.078	0.08	0.32	9	-10000	0	9
GATA3	-0.008	0.14	-10000	0	-0.76	10	10
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.29	0.28	-10000	0	-0.57	109	109
GSK3B	0.014	0.007	-10000	0	-10000	0	0
NR1I3	0.058	0.16	0.48	4	-0.76	2	6
CSN2	0.12	0.14	0.47	7	-0.49	1	8
BRG1/BAF155/BAF170/BAF60A	0.022	0.024	-10000	0	-10000	0	0
NFATC1	0.014	0.003	-10000	0	-10000	0	0
POU2F1	0.015	0.015	-10000	0	-10000	0	0
CDKN1A	0.03	0.042	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.007	-10000	0	-10000	0	0
SFN	0.011	0.038	-10000	0	-0.64	1	1
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.092	0.092	0.38	3	-10000	0	3
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.038	0.21	0.47	3	-0.86	11	14
JUN	-0.2	0.16	-10000	0	-0.65	16	16
IL4	-0.063	0.11	-10000	0	-0.5	4	4
CDK5R1	0.011	0.047	-10000	0	-0.8	1	1
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.15	0.31	-10000	0	-0.62	49	49
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.094	0.091	0.38	3	-10000	0	3
cortisol/GR alpha (monomer)	0.23	0.26	0.68	42	-10000	0	42
NCOA2	0.005	0.075	-10000	0	-0.64	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.17	0.24	-10000	0	-0.71	49	49
AP-1/NFAT1-c-4	-0.41	0.25	-10000	0	-0.83	49	49
AFP	-0.14	0.19	-10000	0	-0.84	15	15
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.1	0.17	0.52	6	-10000	0	6
TP53	0.031	0.065	-10000	0	-0.62	3	3
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.38	0.37	-10000	0	-0.95	79	79
KRT14	-0.22	0.38	-10000	0	-1.2	36	36
TBP	0.024	0	-10000	0	-10000	0	0
CREBBP	0.066	0.087	0.33	11	-10000	0	11
HDAC1	0.012	0.012	-10000	0	-10000	0	0
HDAC2	0.042	0.031	-10000	0	-10000	0	0
AP-1	-0.41	0.25	-10000	0	-0.83	50	50
MAPK14	0.014	0.007	-10000	0	-10000	0	0
MAPK10	-0.017	0.14	-10000	0	-0.65	14	14
MAPK11	0.014	0.007	-10000	0	-10000	0	0
KRT5	-0.26	0.21	-10000	0	-0.93	11	11
interleukin-1 receptor activity	0.029	0.031	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	-0.039	0.21	-10000	0	-0.78	23	23
CGA	-0.055	0.13	-10000	0	-0.76	3	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.2	0.42	143	-10000	0	143
MAPK3	0.014	0.007	-10000	0	-10000	0	0
MAPK1	0.014	0.007	-10000	0	-10000	0	0
ICAM1	-0.14	0.25	-10000	0	-0.73	30	30
NFKB1	-0.007	0.089	-10000	0	-10000	0	0
MAPK8	-0.16	0.15	-10000	0	-0.57	17	17
MAPK9	0.014	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.017	0.16	0.47	6	-0.76	1	7
BAX	0.03	0.042	-10000	0	-10000	0	0
POMC	-0.16	0.31	-10000	0	-0.95	27	27
EP300	0.068	0.088	0.35	7	-10000	0	7
cortisol/GR alpha (dimer)/p53	0.22	0.22	0.59	41	-0.58	1	42
proteasomal ubiquitin-dependent protein catabolic process	0.054	0.062	0.28	1	-10000	0	1
SGK1	0.12	0.13	0.45	1	-1.4	1	2
IL13	-0.21	0.18	-10000	0	-0.84	9	9
IL6	-0.18	0.36	-10000	0	-1.1	33	33
PRKACG	0.001	0.047	-10000	0	-0.8	1	1
IL5	-0.19	0.16	-10000	0	-0.77	8	8
IL2	-0.26	0.19	-10000	0	-0.7	21	21
CDK5	0.013	0.005	-10000	0	-10000	0	0
PRKACB	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.22	0.34	-10000	0	-0.74	74	74
CDK5R1/CDK5	0.002	0.038	-10000	0	-0.61	1	1
NF kappa B1 p50/RelA/PKAc	0.01	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.58	29	-10000	0	29
SMARCA4	0.015	0.003	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.13	0.46	12	-10000	0	12
NF kappa B1 p50/RelA/Cbp	0.065	0.16	0.42	9	-10000	0	9
JUN (dimer)	-0.2	0.16	-10000	0	-0.65	16	16
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.076	0.2	-10000	0	-0.93	12	12
NR3C1	0.14	0.15	0.51	20	-10000	0	20
NR4A1	-0.022	0.13	-10000	0	-0.62	8	8
TIF2/SUV420H1	-0.006	0.054	-10000	0	-0.47	4	4
MAPKKK cascade	0.025	0.16	0.47	6	-0.71	1	7
cortisol/GR alpha (dimer)/Src-1	0.21	0.22	0.59	39	-10000	0	39
PBX1	-0.082	0.23	-10000	0	-0.64	45	45
POU1F1	0.003	0.016	-10000	0	-10000	0	0
SELE	-0.23	0.42	-10000	0	-1.1	52	52
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.13	0.46	12	-10000	0	12
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.2	0.2	0.58	29	-10000	0	29
mol:cortisol	0.12	0.16	0.4	47	-10000	0	47
MMP1	-0.64	0.21	-10000	0	-0.71	271	271

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.038	-10000	0	-0.64	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.013	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.021	0.062	-10000	0	-10000	0	0
IRAK/TOLLIP	0.034	0.003	-10000	0	-10000	0	0
IKBKB	0.013	0	-10000	0	-10000	0	0
IKBKG	0.013	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.24	0.3	-10000	0	-0.58	128	128
IL1A	-0.18	0.34	-10000	0	-0.8	72	72
IL1B	-0.037	0.19	-10000	0	-0.6	30	30
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.016	-10000	0	-10000	0	0
IL1R2	-0.13	0.27	-10000	0	-0.65	64	64
IL1R1	0.013	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.011	0.056	0.22	2	-10000	0	2
TOLLIP	0.013	0	-10000	0	-10000	0	0
TICAM2	0.013	0	-10000	0	-10000	0	0
MAP3K3	0.013	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.073	0.007	-10000	0	-10000	0	0
JUN	0.036	0.07	-10000	0	-10000	0	0
MAP3K7	0.013	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.042	0.12	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.11	0.2	-10000	0	-0.48	70	70
PIK3R1	0.013	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.11	0.19	-10000	0	-0.45	70	70
IL1 beta fragment/IL1R1/IL1RAP	-0.048	0.14	-10000	0	-0.48	28	28
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.029	0.074	-10000	0	-10000	0	0
IRAK1	0.029	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.14	0.22	-10000	0	-0.47	90	90
IRAK4	0.013	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
TRAF6	0.013	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.017	0.079	-10000	0	-10000	0	0
CHUK	0.013	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.048	0.14	-10000	0	-0.48	28	28
IL1 beta/IL1R2	-0.14	0.22	-10000	0	-0.46	90	90
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.037	0.11	-10000	0	-10000	0	0
IRAK3	-0.004	0.12	-10000	0	-0.76	7	7
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.042	0.12	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.03	0.12	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.13	0.22	-10000	0	-0.52	73	73
RELA	0.013	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
MYD88	0.013	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-10000	0	-10000	0	0
IL1RAP	0.011	0.047	-10000	0	-0.8	1	1
UBE2N	0.013	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.034	0.1	-10000	0	-10000	0	0
CASP1	0.011	0.038	-10000	0	-0.64	1	1
IL1RN/IL1R2	-0.23	0.31	-10000	0	-0.59	119	119
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.044	0.13	-10000	0	-0.45	28	28
TMEM189-UBE2V1	0.011	0.005	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.036	0.078	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
IL1RN	-0.18	0.3	-10000	0	-0.64	90	90
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	0.023	0.072	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.003	0.016	-10000	0	-10000	0	0
AES	0.002	0.014	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.01	0.078	-10000	0	-0.61	5	5
SMAD4	0.011	0.038	-10000	0	-0.64	1	1
DKK2	-0.012	0.14	-10000	0	-0.74	10	10
TLE1	0.002	0.014	-10000	0	-10000	0	0
MACF1	0.014	0.001	-10000	0	-10000	0	0
CTNNB1	0.047	0.12	-10000	0	-10000	0	0
WIF1	-0.31	0.33	-10000	0	-0.65	145	145
beta catenin/RanBP3	-0.013	0.082	0.37	7	-10000	0	7
KREMEN2	-0.27	0.39	-10000	0	-0.8	106	106
DKK1	-0.23	0.37	-10000	0	-0.78	93	93
beta catenin/beta TrCP1	0.053	0.11	-10000	0	-10000	0	0
FZD1	0	0.1	-10000	0	-0.8	5	5
AXIN2	0.004	0.16	-10000	0	-1.5	3	3
AXIN1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.013	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.025	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.088	0.065	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.005	0.041	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.058	0.072	-10000	0	-10000	0	0
HNF1A	-0.014	0.11	-10000	0	-0.8	6	6
CTBP1	0.002	0.015	-10000	0	-10000	0	0
MYC	0.016	0.045	-10000	0	-0.53	1	1
RANBP3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.2	0.26	-10000	0	-0.54	112	112
NKD1	-0.015	0.14	-10000	0	-0.76	11	11
TCF4	0.002	0.015	-10000	0	-10000	0	0
TCF3	0.002	0.015	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.011	0.072	-10000	0	-0.48	7	7
Ran/GTP	0	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.008	0.084	0.53	5	-10000	0	5
LEF1	-0.003	0.067	-10000	0	-0.81	2	2
DVL1	0.066	0.06	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.1	0.072	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.34	0.34	-10000	0	-0.62	164	164
LRP6	0.014	0.001	-10000	0	-10000	0	0
CSNK1A1	0.003	0.016	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.006	0.19	-10000	0	-1.1	7	7
WNT1	0.006	0.066	-10000	0	-0.8	2	2
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
PPP2R5D	0.052	0.066	0.36	11	-10000	0	11
APC	0.031	0.073	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.12	0.13	0.25	145	-10000	0	145
CREBBP	0.002	0.015	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.015	0.15	-10000	0	-0.5	1	1
CRKL	-0.011	0.14	-10000	0	-0.4	30	30
HRAS	-0.007	0.15	-10000	0	-0.53	5	5
mol:PIP3	-0.025	0.13	-10000	0	-0.4	29	29
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.013	0	-10000	0	-10000	0	0
GAB1	-0.019	0.14	-10000	0	-0.43	29	29
FOXO3	-0.003	0.13	-10000	0	-0.4	3	3
AKT1	-0.013	0.14	-10000	0	-0.4	29	29
BAD	-0.003	0.13	-10000	0	-0.37	25	25
megakaryocyte differentiation	-0.033	0.16	-10000	0	-0.43	39	39
GSK3B	-0.003	0.13	-10000	0	-0.4	3	3
RAF1	0.006	0.13	-10000	0	-0.42	5	5
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.019	0.14	-10000	0	-0.43	29	29
STAT1	-0.086	0.35	-10000	0	-1.1	29	29
HRAS/SPRED1	-0.049	0.097	-10000	0	-0.42	5	5
cell proliferation	-0.02	0.15	-10000	0	-0.43	29	29
PIK3CA	0.013	0	-10000	0	-10000	0	0
TEC	-0.023	0.15	-10000	0	-0.64	17	17
RPS6KB1	-0.019	0.14	-10000	0	-0.43	29	29
HRAS/SPRED2	-0.049	0.097	-10000	0	-0.42	5	5
LYN/TEC/p62DOK	-0.063	0.14	-10000	0	-0.66	6	6
MAPK3	0.02	0.096	-10000	0	-0.33	1	1
STAP1	-0.056	0.18	-10000	0	-0.44	53	53
GRAP2	-0.007	0.12	-10000	0	-0.74	8	8
JAK2	-0.11	0.25	-10000	0	-0.84	29	29
STAT1 (dimer)	-0.083	0.34	-10000	0	-1	29	29
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.084	0.17	-10000	0	-0.58	10	10
actin filament polymerization	-0.019	0.15	-10000	0	-0.44	29	29
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.059	0.22	-10000	0	-0.59	32	32
PIK3R1	0.013	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.042	0.11	-10000	0	-10000	0	0
PI3K	-0.047	0.12	-10000	0	-0.4	29	29
PTEN	0.013	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.11	0.42	-10000	0	-1.3	29	29
MAPK8	-0.021	0.15	-10000	0	-0.44	29	29
STAT3 (dimer)	-0.018	0.14	-10000	0	-0.42	29	29
positive regulation of transcription	0.022	0.083	-10000	0	-10000	0	0
mol:GDP	-0.071	0.14	-10000	0	-0.6	6	6
PIK3C2B	-0.02	0.15	-10000	0	-0.44	29	29
CBL/CRKL	-0.002	0.13	-10000	0	-0.4	2	2
FER	-0.019	0.14	-10000	0	-0.43	29	29
SH2B3	-0.02	0.15	-10000	0	-0.43	30	30
PDPK1	-0.015	0.12	-10000	0	-0.36	29	29
SNAI2	-0.025	0.16	-10000	0	-0.44	32	32
positive regulation of cell proliferation	-0.046	0.25	-10000	0	-0.74	29	29
KITLG	0.015	0.009	-10000	0	-10000	0	0
cell motility	-0.046	0.25	-10000	0	-0.74	29	29
PTPN6	0.007	0.012	-10000	0	-10000	0	0
EPOR	0.002	0.14	-10000	0	-0.65	7	7
STAT5A (dimer)	-0.03	0.2	-10000	0	-0.6	29	29
SOCS1	-0.054	0.22	-10000	0	-0.8	25	25
cell migration	0.03	0.16	0.43	36	-10000	0	36
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.055	0.22	-10000	0	-0.8	25	25
VAV1	0.003	0.083	-10000	0	-0.64	5	5
GRB10	-0.02	0.15	-10000	0	-0.43	30	30
PTPN11	0.006	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.054	0.14	-10000	0	-0.45	30	30
GO:0007205	0.001	0.009	-10000	0	-10000	0	0
MAP2K1	0.017	0.1	-10000	0	-0.36	1	1
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.093	0.41	-10000	0	-1.3	30	30
MAP2K2	0.017	0.1	-10000	0	-0.36	1	1
SHC/Grb2/SOS1	-0.046	0.12	-10000	0	-0.43	2	2
STAT5A	-0.032	0.21	-10000	0	-0.62	29	29
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.024	0.15	-10000	0	-0.44	32	32
SHC/GRAP2	-0.015	0.09	-10000	0	-0.56	8	8
PTPRO	-0.034	0.16	-10000	0	-0.44	39	39
SH2B2	-0.02	0.15	-10000	0	-0.44	29	29
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.031	0.16	-10000	0	-0.44	36	36
CREBBP	0.035	0.014	-10000	0	-10000	0	0
BCL2	0.002	0.17	-10000	0	-1.2	4	4

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.002	0.035	-9999	-0.61	1	1
VLDLR	0.003	0.083	-9999	-0.64	5	5
CRKL	0.011	0.047	-9999	-0.8	1	1
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.011	0.047	-9999	-0.8	1	1
ITGA3	-0.026	0.18	-9999	-0.79	15	15
RELN/VLDLR/Fyn	-0.083	0.16	-9999	-0.4	63	63
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.037	-9999	-0.45	1	1
AKT1	-0.031	0.13	-9999	-0.54	4	4
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	-0.022	0.16	-9999	-0.8	12	12
RELN/LRP8/DAB1	-0.1	0.19	-9999	-0.42	72	72
LRPAP1/LRP8	-0.016	0.098	-9999	-0.61	8	8
RELN/LRP8/DAB1/Fyn	-0.095	0.18	-9999	-0.54	21	21
DAB1/alpha3/beta1 Integrin	-0.11	0.18	-9999	-0.72	7	7
long-term memory	-0.16	0.23	-9999	-0.77	18	18
DAB1/LIS1	-0.09	0.17	-9999	-0.75	6	6
DAB1/CRLK/C3G	-0.088	0.16	-9999	-0.72	7	7
PIK3CA	0.013	0	-9999	-10000	0	0
DAB1/NCK2	-0.091	0.17	-9999	-0.75	6	6
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.12	0.29	-9999	-0.72	56	56
CDK5R1	0.011	0.047	-9999	-0.8	1	1
RELN	-0.11	0.26	-9999	-0.64	57	57
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.09	0.18	-9999	-0.42	64	64
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.16	0.23	-9999	-0.56	54	54
MAPK8	0.009	0.053	-9999	-0.64	2	2
RELN/VLDLR/DAB1	-0.093	0.18	-9999	-0.4	70	70
ITGB1	0.011	0.047	-9999	-0.8	1	1
MAP1B	-0.08	0.22	-9999	-0.8	11	11
RELN/LRP8	-0.088	0.18	-9999	-0.42	63	63
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.098	0.19	-9999	-0.54	23	23
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.032	0.14	-9999	-0.6	16	16
RAP1A	-0.036	0.18	-9999	-0.67	7	7
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.011	0.047	-9999	-0.8	1	1
CRLK/C3G	-0.002	0.035	-9999	-0.61	1	1
GRIN2B	-0.003	0.08	-9999	-0.8	3	3
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.012	0.11	-9999	-0.42	7	7
neuron adhesion	-0.041	0.19	-9999	-0.63	8	8
LRP8	-0.008	0.13	-9999	-0.8	8	8
GSK3B	-0.021	0.13	-9999	-0.5	4	4
RELN/VLDLR/DAB1/Fyn	-0.088	0.17	-9999	-0.56	13	13
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.042	0.14	-9999	-0.57	4	4
CDK5	0.013	0	-9999	-10000	0	0
MAPT	-0.25	0.3	-9999	-0.6	131	131
neuron migration	-0.025	0.18	-9999	-0.56	6	6
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.012	0.11	-9999	-0.42	7	7
RELN/VLDLR	-0.085	0.16	-9999	-0.56	8	8

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.05	-9999	-0.61	2	2
alphaV beta3 Integrin	-0.04	0.14	-9999	-0.52	23	23
PTK2	-0.002	0.15	-9999	-0.64	4	4
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
CDKN1B	-0.047	0.12	-9999	-0.4	27	27
VEGFA	0.011	0.047	-9999	-0.8	1	1
ILK	-0.047	0.12	-9999	-0.4	27	27
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.042	0.11	-9999	-0.49	3	3
PTK2B	0.018	0.11	-9999	-0.46	14	14
alphaV/beta3 Integrin/JAM-A	-0.073	0.18	-9999	-0.5	40	40
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.028	0.12	-9999	-0.53	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.037	0.11	-9999	-0.48	5	5
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.013	0.089	-9999	-0.42	3	3
alphaV/beta3 Integrin/Syndecan-1	-0.024	0.11	-9999	-0.53	14	14
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.29	0.25	-9999	-0.82	26	26
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.32	0.28	-9999	-0.55	178	178
RPS6KB1	-0.24	0.26	-9999	-0.75	26	26
TLN1	0.011	0.047	-9999	-0.8	1	1
MAPK3	-0.12	0.16	-9999	-0.59	21	21
GPR124	0.008	0.066	-9999	-0.8	2	2
MAPK1	-0.12	0.16	-9999	-0.59	21	21
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.086	0.2	-9999	-0.53	49	49
cell adhesion	-0.023	0.1	-9999	-0.46	12	12
ANGPTL3	-0.001	0.066	-9999	-0.8	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	-0.003	0.043	-9999	-0.53	2	2
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.013	0	-9999	-10000	0	0
ITGB3	-0.017	0.15	-9999	-0.76	12	12
IGF1	-0.054	0.2	-9999	-0.67	30	30
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.027	0.12	-9999	-0.56	15	15
apoptosis	0.006	0.076	-9999	-0.75	3	3
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.024	0.11	-9999	-0.53	14	14
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.075	0.2	-9999	-0.56	41	41
CSF1	0.009	0.053	-9999	-0.64	2	2
PIK3C2A	-0.047	0.12	-9999	-0.4	27	27
PI4 Kinase/Pyk2	-0.063	0.15	-9999	-0.74	5	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.11	-9999	-0.5	14	14
FAK1/Vinculin	0.009	0.12	-9999	-0.51	3	3
alphaV beta3/Integrin/ppsTEM5	-0.028	0.12	-9999	-0.56	15	15
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.059	0.23	-9999	-0.8	27	27
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	-0.012	0.13	-9999	-0.68	11	11
F11R	0.005	0.1	-9999	-0.51	11	11
alphaV/beta3 Integrin/Lactadherin	-0.024	0.11	-9999	-0.53	14	14
alphaV/beta3 Integrin/TGFBR2	-0.024	0.11	-9999	-0.53	14	14
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.007	0.052	-9999	-0.48	2	2
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.024	0.11	-9999	-0.49	15	15
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.44	0.4	-9999	-0.8	170	170
alphaV/beta3 Integrin/Pyk2	-0.023	0.1	-9999	-0.46	14	14
SDC1	0.013	0	-9999	-10000	0	0
VAV3	0.011	0.11	-9999	-0.44	2	2
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.009	0.12	-9999	-0.51	3	3
cell migration	0.019	0.12	-9999	-0.45	3	3
ITGAV	0.006	0.076	-9999	-0.75	3	3
PI3K	-0.065	0.16	-9999	-0.79	5	5
SPP1	-0.45	0.4	-9999	-0.8	171	171
KDR	0.011	0.047	-9999	-0.8	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.006	0.076	-9999	-0.75	3	3
COL4A3	-0.084	0.26	-9999	-0.76	38	38
angiogenesis	-0.094	0.18	-9999	-0.68	13	13
Rac1/GTP	-0.026	0.085	-9999	-10000	0	0
EDIL3	-0.067	0.24	-9999	-0.77	31	31
cell proliferation	-0.024	0.11	-9999	-0.52	14	14

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.008	0.061	-10000	0	-0.62	2	2
HDAC1	0.001	0.007	-10000	0	-10000	0	0
AES	0.012	0.001	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.011	0.038	-10000	0	-0.64	1	1
LRP6/FZD1	-0.01	0.078	-10000	0	-0.61	5	5
TLE1	0.013	0.001	-10000	0	-10000	0	0
AP1	-0.037	0.14	-10000	0	-0.32	51	51
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	0.013	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.038	0.048	-10000	0	-10000	0	0
NICD/RBPSUH	-0.004	0.05	-10000	0	-0.61	2	2
WIF1	-0.31	0.33	-10000	0	-0.65	145	145
NOTCH1	-0.005	0.053	-10000	0	-0.65	2	2
PSENEN	0.011	0.047	-10000	0	-0.8	1	1
KREMEN2	-0.27	0.39	-10000	0	-0.8	106	106
DKK1	-0.23	0.37	-10000	0	-0.78	93	93
beta catenin/beta TrCP1	0.017	0.04	-10000	0	-10000	0	0
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	0.002	0.024	-10000	0	-0.27	1	1
CtBP/CBP/TCF1/TLE1/AES	-0.002	0.044	-10000	0	-10000	0	0
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.092	0.24	-10000	0	-0.64	49	49
JUN	0.013	0	-10000	0	-10000	0	0
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.01	0.043	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.2	0.26	-10000	0	-0.54	112	112
HNF1A	-0.004	0.11	-10000	0	-0.8	6	6
CTBP1	0.012	0.001	-10000	0	-10000	0	0
MYC	0.025	0.014	-10000	0	-10000	0	0
NKD1	-0.015	0.14	-10000	0	-0.76	11	11
FZD1	0	0.1	-10000	0	-0.8	5	5
NOTCH1 precursor/Deltex homolog 1	-0.005	0.064	-10000	0	-0.78	2	2
apoptosis	-0.037	0.14	-10000	0	-0.31	51	51
Delta 1/NOTCHprecursor	-0.008	0.061	-10000	0	-0.61	2	2
DLL1	0.005	0.075	-10000	0	-0.64	4	4
PPARD	0.025	0.014	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.026	-10000	0	-10000	0	0
APC	0.002	0.024	-10000	0	-0.27	1	1
DVL1	-0.026	0.026	-10000	0	-10000	0	0
CSNK2A1	0.014	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.34	0.34	-10000	0	-0.62	164	164
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.001	0.18	-10000	0	-1.1	7	7
WNT1	0.005	0.066	-10000	0	-0.8	2	2
Axin1/APC/beta catenin	0.023	0.04	-10000	0	-10000	0	0
DKK2	-0.011	0.14	-10000	0	-0.74	10	10
NOTCH1 precursor/DVL1	-0.011	0.049	-10000	0	-0.61	2	2
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.005	0.064	-10000	0	-0.78	2	2
PPP2R5D	-0.001	0.063	0.31	11	-10000	0	11
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.18	-10000	0	-0.48	15	15
RBPJ	0.013	0	-10000	0	-10000	0	0
CREBBP	0.017	0.003	-10000	0	-10000	0	0

×

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	0.026	0.054	-9999	-0.39	5	5
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.024	0.063	-9999	-0.42	6	6
MAPK12	-0.011	0.14	-9999	-0.52	14	14
CCND1	-0.002	0.086	-9999	-0.45	6	6
p38 gamma/SNTA1	-0.003	0.13	-9999	-0.49	14	14
MAP2K3	0.011	0.038	-9999	-0.64	1	1
PKN1	0.008	0.066	-9999	-0.8	2	2
G2/M transition checkpoint	-0.01	0.14	-9999	-0.52	14	14
MAP2K6	0.004	0.093	-9999	-0.39	14	14
MAPT	-0.14	0.19	-9999	-0.35	131	131
MAPK13	0.017	0.063	-9999	-0.47	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0.037	-9999	-0.36	3	3

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.13	0.24	-10000	0	-0.54	75	75
cell-cell adhesion	0.12	0.16	0.56	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	-0.12	0.19	-10000	0	-0.45	67	67
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.012	0.069	-10000	0	-0.4	9	9
Ephrin B1/EPHB1	-0.033	0.12	-10000	0	-0.5	20	20
HRAS/GDP	-0.057	0.11	-10000	0	-0.57	2	2
Ephrin B/EPHB1/GRB7	-0.052	0.14	-10000	0	-0.47	19	19
Endophilin/SYNJ1	-0.081	0.2	-10000	0	-0.42	67	67
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.046	0.13	-10000	0	-0.47	16	16
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	0.003	0.089	-10000	0	-0.76	4	4
PAK1	-0.096	0.22	-10000	0	-0.68	8	8
HRAS	0.013	0	-10000	0	-10000	0	0
RRAS	-0.082	0.2	-10000	0	-0.43	67	67
DNM1	-0.043	0.21	-10000	0	-0.8	21	21
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.14	-10000	0	-0.45	16	16
lamellipodium assembly	-0.12	0.16	-10000	0	-0.56	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.009	0.097	-10000	0	-0.5	2	2
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	-0.17	0.34	-10000	0	-0.8	67	67
EPHB3	-0.006	0.11	-10000	0	-0.64	9	9
EPHB1	-0.037	0.19	-10000	0	-0.75	20	20
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.054	0.11	-10000	0	-0.52	3	3
Ephrin B/EPHB2	-0.12	0.2	-10000	0	-0.46	67	67
Ephrin B/EPHB3	-0.03	0.099	-10000	0	-0.68	1	1
JNK cascade	-0.093	0.22	-10000	0	-10000	0	0
Ephrin B/EPHB1	-0.047	0.13	-10000	0	-0.48	16	16
RAP1/GDP	-0.045	0.096	-10000	0	-0.48	2	2
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.025	0.16	-10000	0	-0.64	18	18
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.14	0.22	-10000	0	-0.49	81	81
RAP1B	0.011	0.047	-10000	0	-0.8	1	1
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.17	-10000	0	-0.62	3	3
Rap1/GTP	-0.12	0.16	-10000	0	-0.57	3	3
axon guidance	-0.13	0.23	-10000	0	-0.53	75	75
MAPK3	0.026	0.088	-10000	0	-0.44	2	2
MAPK1	0.026	0.088	-10000	0	-0.44	2	2
Rac1/GDP	-0.012	0.12	-10000	0	-0.5	2	2
actin cytoskeleton reorganization	-0.091	0.13	-10000	0	-0.44	3	3
CDC42/GDP	-0.012	0.12	-10000	0	-0.5	2	2
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.01	0.12	-10000	0	-0.64	11	11
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.042	0.13	-10000	0	-0.54	1	1
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.11	0.16	-10000	0	-0.55	3	3
PTK2	0.029	0.046	-10000	0	-10000	0	0
MAP4K4	-0.094	0.22	-10000	0	-10000	0	0
SRC	0.013	0	-10000	0	-10000	0	0
KALRN	-0.025	0.16	-10000	0	-0.64	18	18
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.047	0.17	-10000	0	-0.49	5	5
MAP2K1	0.018	0.092	-10000	0	-0.47	2	2
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.14	0.21	-10000	0	-0.48	81	81
cell migration	0.022	0.1	-10000	0	-0.54	2	2
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	-0.082	0.2	-10000	0	-0.43	67	67
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.3	0.25	-10000	0	-0.7	62	62
HRAS/GTP	-0.12	0.18	-10000	0	-0.61	3	3
Ephrin B1/EPHB1-2	-0.14	0.22	-10000	0	-0.48	87	87
cell adhesion mediated by integrin	0.014	0.087	0.41	2	-10000	0	2
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.13	0.19	-10000	0	-0.66	3	3
RAC1-CDC42/GTP	-0.12	0.17	-10000	0	-0.58	6	6
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.043	0.094	-10000	0	-0.48	2	2
ruffle organization	-0.068	0.2	-10000	0	-0.57	3	3
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	-0.1	0.24	-10000	0	-0.82	11	11
Ephrin B/EPHB2/KALRN	-0.14	0.21	-10000	0	-0.47	72	72
ROCK1	0.016	0.066	-10000	0	-0.36	9	9
RAS family/GDP	-0.088	0.13	-10000	0	-0.5	1	1
Rac1/GTP	-0.12	0.17	-10000	0	-0.6	3	3
Ephrin B/EPHB1/Src/Paxillin	0.003	0.1	-10000	0	-0.55	2	2

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.011	-10000	0	-10000	0	0
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.053	0.17	-10000	0	-0.53	13	13
AKT1	0.002	0.031	-10000	0	-10000	0	0
GSC	-0.017	0.18	-10000	0	-0.63	23	23
NKX2-5	-0.2	0.35	-10000	0	-0.79	80	80
muscle cell differentiation	0.15	0.22	0.67	28	-10000	0	28
SMAD2-3/SMAD4/SP1	-0.059	0.1	-10000	0	-10000	0	0
SMAD4	-0.001	0.054	-10000	0	-0.61	1	1
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.014	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.001	0.048	-10000	0	-0.53	2	2
SMAD3/SMAD4/VDR	0.005	0.039	-10000	0	-10000	0	0
MYC	0.025	0.032	-10000	0	-10000	0	0
CDKN2B	-0.22	0.56	-10000	0	-1.4	57	57
AP1	-0.02	0.13	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.057	0.038	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.054	0.16	-10000	0	-0.59	7	7
SP3	0.016	0.001	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.08	0.26	-10000	0	-0.79	34	34
SMAD3/SMAD4/GR	0.035	0.073	-10000	0	-10000	0	0
GATA3	-0.013	0.14	-10000	0	-0.76	10	10
SKI/SIN3/HDAC complex/NCoR1	0.058	0.017	-10000	0	-10000	0	0
MEF2C/TIF2	-0.16	0.25	-10000	0	-0.74	24	24
endothelial cell migration	0.37	0.32	0.64	180	-10000	0	180
MAX	0.035	0.02	-10000	0	-10000	0	0
RBBP7	0.014	0.002	-10000	0	-10000	0	0
RBBP4	0.014	0.002	-10000	0	-10000	0	0
RUNX2	0.011	0.038	-10000	0	-0.64	1	1
RUNX3	0.005	0.081	-10000	0	-0.8	3	3
RUNX1	0.013	0	-10000	0	-10000	0	0
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.035	0.02	-10000	0	-10000	0	0
VDR	0.013	0	-10000	0	-10000	0	0
CDKN1A	-0.001	0.095	-10000	0	-10000	0	0
KAT2B	-0.019	0.13	-10000	0	-0.65	13	13
SMAD2/SMAD2/SMAD4/FOXH1	-0.06	0.18	-10000	0	-0.54	34	34
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.014	0.002	-10000	0	-10000	0	0
SERPINE1	-0.37	0.33	-10000	0	-0.64	180	180
SMAD3/SMAD4/ATF2	0.009	0.054	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.002	0.084	-10000	0	-0.52	4	4
SAP30	0.014	0.002	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.002	0.028	-10000	0	-10000	0	0
JUN	-0.005	0.13	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.001	0.1	-10000	0	-0.58	5	5
TFE3	0	0.017	-10000	0	-10000	0	0
COL1A2	-0.34	0.35	-10000	0	-0.68	155	155
mesenchymal cell differentiation	-0.008	0.059	0.39	1	-10000	0	1
DLX1	-0.38	0.41	-10000	0	-0.8	146	146
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.087	0.24	-10000	0	-0.63	49	49
SMAD3/SMAD4/Max	0.035	0.073	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.002	0.01	-10000	0	-10000	0	0
ZBTB17	0.023	0.025	-10000	0	-10000	0	0
LAMC1	0.005	0.048	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.007	0.066	-10000	0	-0.64	1	1
IRF7	0	0.1	-10000	0	-0.8	5	5
ESR1	-0.009	0.18	-10000	0	-0.74	17	17
HNF4A	-0.07	0.24	-10000	0	-0.8	30	30
MEF2C	-0.15	0.28	-10000	0	-0.76	24	24
SMAD2-3/SMAD4	-0.003	0.067	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.005	0.018	-10000	0	-10000	0	0
IGHV3OR16-13	-0.002	0.012	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0.047	-10000	0	-0.8	1	1
CREBBP	0.007	0.01	-10000	0	-10000	0	0
SKIL	0.013	0	-10000	0	-10000	0	0
HDAC1	0.014	0.002	-10000	0	-10000	0	0
HDAC2	0.014	0.002	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.009	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.009	0.05	-10000	0	-10000	0	0
MSG1/HSC70	0.014	0.053	-10000	0	-0.61	2	2
SMAD2	0.002	0.036	-10000	0	-10000	0	0
SMAD3	0.004	0.051	-10000	0	-0.59	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.023	0.043	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.025	0.084	-10000	0	-0.39	14	14
NCOR1	0.014	0.002	-10000	0	-10000	0	0
NCOA2	0.005	0.075	-10000	0	-0.64	4	4
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.088	0.19	-10000	0	-0.48	56	56
SMAD2-3/SMAD4/SP1/MIZ-1	-0.048	0.098	-10000	0	-10000	0	0
IFNB1	0.01	0.13	-10000	0	-0.68	7	7
SMAD3/SMAD4/MEF2C	-0.14	0.27	-10000	0	-0.76	21	21
CITED1	0.008	0.066	-10000	0	-0.8	2	2
SMAD2-3/SMAD4/ARC105	0.004	0.068	-10000	0	-0.54	1	1
RBL1	0.013	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.054	0.22	-10000	0	-0.5	57	57
RUNX1-3/PEBPB2	-0.005	0.052	-10000	0	-0.53	3	3
SMAD7	-0.042	0.13	-10000	0	-10000	0	0
MYC/MIZ-1	0.03	0.063	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.13	0.15	0.35	4	-0.4	4	8
IL10	0	0.17	-10000	0	-0.69	12	12
PIASy/HDAC complex	0.023	0.012	-10000	0	-10000	0	0
PIAS3	0.006	0.008	-10000	0	-10000	0	0
CDK2	0.007	0.009	-10000	0	-10000	0	0
IL5	0.002	0.14	-10000	0	-0.67	6	6
CDK4	0.007	0.01	-10000	0	-10000	0	0
PIAS4	0.023	0.012	-10000	0	-10000	0	0
ATF3	0.002	0.092	-10000	0	-0.71	5	5
SMAD3/SMAD4/SP1	-0.077	0.087	-10000	0	-10000	0	0
FOXG1	-0.1	0.26	-10000	0	-0.72	44	44
FOXO3	0.01	0.042	-10000	0	-10000	0	0
FOXO1	0.01	0.042	-10000	0	-10000	0	0
FOXO4	0.007	0.057	-10000	0	-0.47	2	2
heart looping	-0.14	0.28	-10000	0	-0.75	24	24
CEBPB	0.008	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.27	0.29	-10000	0	-0.57	146	146
MYOD1	-0.11	0.26	-10000	0	-0.65	56	56
SMAD3/SMAD4/HNF4	-0.049	0.18	-10000	0	-0.56	30	30
SMAD3/SMAD4/GATA3	-0.012	0.13	-10000	0	-0.56	9	9
SnoN/SIN3/HDAC complex/NCoR1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.013	0.068	-10000	0	-0.47	3	3
SMAD3/SMAD4/SP1-3	-0.056	0.07	-10000	0	-10000	0	0
MED15	0.011	0.047	-10000	0	-0.8	1	1
SP1	-0.053	0.075	-10000	0	-10000	0	0
SIN3B	0.014	0.002	-10000	0	-10000	0	0
SIN3A	0.014	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.18	0.28	-10000	0	-0.54	100	100
ITGB5	-0.012	0.093	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.069	0.18	-10000	0	-0.45	39	39
AR	-0.11	0.26	-10000	0	-0.65	57	57
negative regulation of cell growth	0.025	0.056	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.075	0.18	-10000	0	-0.45	41	41
E2F5	0.013	0	-10000	0	-10000	0	0
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.054	0.15	-10000	0	-0.5	11	11
SMAD2-3/SMAD4/FOXO1-3a-4	-0.026	0.15	-10000	0	-0.38	2	2
TFDP1	0.011	0.047	-10000	0	-0.8	1	1
SMAD3/SMAD4/AP1	-0.012	0.14	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.008	0.059	-10000	0	-0.39	1	1
TGIF2	0.011	0.047	-10000	0	-0.8	1	1
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	0.013	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.22	0.37	-10000	0	-0.8	85	85
Jak2/Leptin Receptor	-0.074	0.1	-10000	0	-0.4	3	3
PTP1B/AKT1	-0.029	0.078	0.23	1	-10000	0	1
FYN	0.011	0.047	-10000	0	-0.8	1	1
p210 bcr-abl/PTP1B	-0.041	0.087	0.26	1	-0.32	2	3
EGFR	-0.017	0.14	-10000	0	-0.8	10	10
EGF/EGFR	-0.13	0.16	-10000	0	-0.38	78	78
CSF1	0.009	0.053	-10000	0	-0.64	2	2
AKT1	0.013	0.001	-10000	0	-10000	0	0
INSR	0.013	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.12	0.21	0.23	1	-0.53	55	56
Insulin Receptor/Insulin	-0.033	0.043	-10000	0	-10000	0	0
HCK	0.004	0.084	-10000	0	-0.72	4	4
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.031	0.083	0.25	1	-0.33	1	2
EGF	-0.14	0.28	-10000	0	-0.65	69	69
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.062	0.11	0.25	1	-0.36	11	12
TXN	0.01	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.036	0.067	-10000	0	-10000	0	0
cell migration	0.041	0.087	0.32	2	-0.26	1	3
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.13	0.27	-10000	0	-0.65	64	64
ITGA2B	-0.041	0.2	-10000	0	-0.8	20	20
CSF1R	0.009	0.053	-10000	0	-0.64	2	2
Prolactin Receptor/Prolactin	-0.1	0.21	-10000	0	-0.49	66	66
FGR	0.011	0.047	-10000	0	-0.8	1	1
PTP1B/p130 Cas	-0.032	0.082	-10000	0	-10000	0	0
Crk/p130 Cas	-0.036	0.067	-10000	0	-10000	0	0
DOK1	-0.079	0.15	0.25	1	-0.39	13	14
JAK2	-0.07	0.12	-10000	0	-0.38	12	12
Jak2/Leptin Receptor/Leptin	-0.086	0.12	-10000	0	-0.49	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.042	0.088	0.26	1	-0.32	2	3
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.13	0.31	-10000	0	-0.79	55	55
SRC	0	0.037	-10000	0	-10000	0	0
ITGB3	-0.018	0.15	-10000	0	-0.76	12	12
CAT1/PTP1B	-0.14	0.16	0.26	1	-0.44	24	25
CAPN1	0.011	0.005	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.022	0.037	-10000	0	-10000	0	0
mol:H2O2	0	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	-0.076	0.11	-10000	0	-0.44	2	2
negative regulation of transcription	-0.069	0.12	-10000	0	-0.38	12	12
FCGR2A	-0.046	0.21	-10000	0	-0.8	22	22
FER	0.01	0.006	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.063	0.19	-10000	0	-0.62	31	31
BLK	-0.12	0.3	-10000	0	-0.77	53	53
Insulin Receptor/Insulin/Shc	0	0.002	-10000	0	-10000	0	0
RHOA	0.011	0.005	-10000	0	-10000	0	0
LEPR	0.013	0.001	-10000	0	-10000	0	0
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.004	-10000	0	-10000	0	0
TRPV6	-0.13	0.16	-10000	0	-0.46	33	33
PRL	-0.004	0.08	-10000	0	-0.8	3	3
SOCS3	0.018	0.082	-10000	0	-1.4	1	1
SPRY2	0.004	0.075	-10000	0	-0.65	4	4
Insulin Receptor/Insulin/IRS1	0	0.002	-10000	0	-10000	0	0
CSF1/CSF1R	-0.041	0.074	-10000	0	-0.39	1	1
Ras protein signal transduction	0.03	0.028	-10000	0	-10000	0	0
IRS1	0.013	0	-10000	0	-10000	0	0
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.11	0.26	-10000	0	-0.7	50	50
STAT5B	-0.048	0.085	0.21	1	-0.29	4	5
STAT5A	-0.048	0.085	0.21	1	-0.29	4	5
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.16	0.26	-10000	0	-0.56	85	85
CSN2	-0.025	0.09	-10000	0	-0.66	1	1
PIK3CA	0.013	0	-10000	0	-10000	0	0
LAT	-0.027	0.093	-10000	0	-0.32	14	14
YBX1	0.02	0.002	-10000	0	-10000	0	0
LCK	-0.014	0.15	-10000	0	-0.8	10	10
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.21	0.36	-10000	0	-0.8	83	83

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.005	0.12	-9999	-0.8	7	7
Syndecan-3/Src/Cortactin	-0.12	0.16	-9999	-0.59	7	7
Syndecan-3/Neurocan	-0.012	0.07	-9999	-0.45	7	7
POMC	-0.067	0.24	-9999	-0.77	31	31
EGFR	-0.014	0.15	-9999	-0.8	10	10
Syndecan-3/EGFR	-0.016	0.082	-9999	-0.44	11	11
AGRP	0.005	0.006	-9999	-10000	0	0
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.011	0.047	-9999	-0.8	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.009	0.12	-9999	-0.8	7	7
long-term memory	-0.012	0.069	-9999	-0.42	8	8
Syndecan-3/IL8	-0.097	0.18	-9999	-0.45	65	65
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	-0.014	0.092	-9999	-0.61	7	7
FYN	0.011	0.047	-9999	-0.8	1	1
limb bud formation	-0.001	0.021	-9999	-0.36	1	1
MC4R	0.006	0.007	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PTN	-0.23	0.32	-9999	-0.64	111	111
FGFR/FGF/Syndecan-3	-0.001	0.022	-9999	-0.37	1	1
neuron projection morphogenesis	-0.12	0.16	-9999	-0.69	5	5
Syndecan-3/AgRP	-0.001	0.021	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.001	0.019	-9999	-10000	0	0
Fyn/Cortactin	-0.016	0.098	-9999	-0.61	8	8
SDC3	-0.002	0.022	-9999	-0.37	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.096	0.18	-9999	-0.44	65	65
IL8	-0.16	0.33	-9999	-0.8	65	65
Syndecan-3/Fyn/Cortactin	-0.013	0.071	-9999	-0.43	8	8
Syndecan-3/CASK	-0.001	0.021	-9999	-0.35	1	1
alpha-MSH/MC4R	-0.06	0.18	-9999	-0.59	31	31
Gamma Secretase	-0.001	0.026	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.012	0.06	-10000	0	-0.79	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.025	0.14	0.51	11	-10000	0	11
IL27/IL27R/JAK1	-0.073	0.17	-10000	0	-0.71	9	9
TBX21	-0.084	0.26	-10000	0	-0.68	29	29
IL12B	-0.079	0.26	-10000	0	-0.81	33	33
IL12A	-0.006	0.088	-10000	0	-0.48	10	10
IL6ST	-0.004	0.099	-10000	0	-0.65	7	7
IL27RA/JAK1	-0.004	0.1	-10000	0	-0.57	9	9
IL27	-0.027	0.17	-10000	0	-0.82	13	13
TYK2	0.013	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.023	0.13	-10000	0	-0.63	6	6
T-helper 2 cell differentiation	0.025	0.14	0.51	11	-10000	0	11
T cell proliferation during immune response	0.025	0.14	0.51	11	-10000	0	11
MAPKKK cascade	-0.025	0.14	-10000	0	-0.51	11	11
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	-0.049	0.22	-10000	0	-0.8	23	23
IL12RB1	-0.073	0.25	-10000	0	-0.8	32	32
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.14	0.33	-10000	0	-0.69	66	66
IL27/IL27R/JAK2/TYK2	-0.026	0.14	-10000	0	-0.52	11	11
positive regulation of T cell mediated cytotoxicity	-0.025	0.14	-10000	0	-0.51	11	11
STAT1 (dimer)	-0.16	0.29	0.52	1	-0.88	28	29
JAK2	0.012	0.007	-10000	0	-10000	0	0
JAK1	0.013	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.018	0.14	-10000	0	-0.54	7	7
T cell proliferation	-0.05	0.18	-10000	0	-0.56	17	17
IL12/IL12R/TYK2/JAK2	-0.066	0.2	-10000	0	-0.62	23	23
IL17A	-0.024	0.13	-10000	0	-0.63	6	6
mast cell activation	0.025	0.14	0.51	11	-10000	0	11
IFNG	-0.013	0.048	-10000	0	-0.11	59	59
T cell differentiation	-0.006	0.009	-10000	0	-0.025	31	31
STAT3 (dimer)	-0.018	0.14	-10000	0	-0.54	7	7
STAT5A (dimer)	-0.018	0.14	-10000	0	-0.54	7	7
STAT4 (dimer)	-0.027	0.15	-10000	0	-0.57	9	9
STAT4	-0.002	0.11	-10000	0	-0.78	6	6
T cell activation	-0.006	0.018	0.092	9	-10000	0	9
IL27R/JAK2/TYK2	-0.031	0.11	-10000	0	-0.6	6	6
GATA3	-0.005	0.15	-10000	0	-0.73	10	10
IL18	-0.004	0.088	-10000	0	-0.48	10	10
positive regulation of mast cell cytokine production	-0.017	0.13	-10000	0	-0.53	7	7
IL27/EBI3	-0.03	0.16	-10000	0	-0.61	20	20
IL27RA	-0.013	0.11	-10000	0	-0.62	9	9
IL6	-0.048	0.2	-10000	0	-0.66	28	28
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.013	0.062	0.38	1	-10000	0	1
IL1B	-0.048	0.18	-10000	0	-0.61	29	29
EBI3	-0.007	0.11	-10000	0	-0.74	7	7
TNF	-0.018	0.13	-10000	0	-0.58	15	15

×

LPA receptor mediated events

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
GNB1/GNG2	-0.057	0.12	-9999	-0.76	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.022	0.048	-9999	-10000	0	0
AP1	-0.097	0.14	-9999	-0.55	8	8
mol:PIP3	-0.055	0.1	-9999	-0.63	1	1
AKT1	-0.034	0.071	-9999	-0.5	2	2
PTK2B	-0.008	0.079	-9999	-0.28	2	2
RHOA	0.003	0.063	-9999	-10000	0	0
PIK3CB	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	0.008	0.07	-9999	-0.46	2	2
MAGI3	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.031	0.12	-9999	-0.34	10	10
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.13	0.17	-9999	-0.45	24	24
NF kappa B1 p50/RelA	-0.039	0.088	-9999	-0.56	2	2
endothelial cell migration	-0.13	0.31	-9999	-0.72	66	66
ADCY4	-0.015	0.13	-9999	-0.48	8	8
ADCY5	-0.059	0.15	-9999	-0.59	10	10
ADCY6	-0.022	0.14	-9999	-0.57	9	9
ADCY7	-0.015	0.13	-9999	-0.48	8	8
ADCY1	-0.023	0.13	-9999	-0.48	8	8
ADCY2	-0.08	0.15	-9999	-0.56	11	11
ADCY3	-0.015	0.13	-9999	-0.48	8	8
ADCY8	-0.023	0.13	-9999	-0.49	8	8
ADCY9	-0.015	0.13	-9999	-0.48	8	8
GSK3B	0	0.076	-9999	-10000	0	0
arachidonic acid secretion	-0.008	0.12	-9999	-0.46	7	7
GNG2	0.011	0.047	-9999	-0.8	1	1
TRIP6	0.015	0.025	-9999	-10000	0	0
GNAO1	-0.043	0.14	-9999	-0.47	8	8
HRAS	0.013	0	-9999	-10000	0	0
NFKBIA	0.011	0.082	-9999	-0.43	2	2
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.004	0.09	-9999	-0.9	3	3
JUN	0.013	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.019	0.049	-9999	-0.62	1	1
TIAM1	-0.007	0.11	-9999	-1.1	3	3
PIK3R1	0.013	0.001	-9999	-10000	0	0
mol:IP3	0.008	0.071	-9999	-0.47	2	2
PLCB3	0.01	0.051	-9999	-0.57	1	1
FOS	-0.092	0.24	-9999	-0.64	49	49
positive regulation of mitosis	-0.008	0.12	-9999	-0.46	7	7
LPA/LPA1-2-3	-0.06	0.12	-9999	-0.81	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	-0.004	0.093	-9999	-0.43	1	1
GNAZ	-0.051	0.16	-9999	-0.53	12	12
EGFR/PI3K-beta/Gab1	-0.057	0.1	-9999	-0.67	1	1
positive regulation of dendritic cell cytokine production	-0.06	0.12	-9999	-0.8	1	1
LPA/LPA2/MAGI-3	-0.017	0.034	-9999	-10000	0	0
ARHGEF1	-0.02	0.12	-9999	-0.62	3	3
GNAI2	-0.039	0.14	-9999	-0.47	6	6
GNAI3	-0.039	0.14	-9999	-0.47	6	6
GNAI1	-0.041	0.14	-9999	-0.46	7	7
LPA/LPA3	-0.03	0.07	-9999	-0.48	4	4
LPA/LPA2	-0.024	0.048	-9999	-10000	0	0
LPA/LPA1	-0.077	0.15	-9999	-0.36	66	66
HB-EGF/EGFR	-0.41	0.25	-9999	-0.54	232	232
HBEGF	-0.46	0.27	-9999	-0.61	230	230
mol:DAG	0.008	0.071	-9999	-0.47	2	2
cAMP biosynthetic process	-0.028	0.13	-9999	-0.56	7	7
NFKB1	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
GNB1	0.013	0.001	-9999	-10000	0	0
LYN	0.011	0.082	-9999	-0.43	2	2
GNAQ	0.001	0.055	-9999	-0.33	4	4
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	0.005	0.075	-9999	-0.64	4	4
LPAR1	-0.034	0.12	-9999	-0.69	6	6
IL8	-0.24	0.18	-9999	-0.49	62	62
PTK2	-0.021	0.12	-9999	-0.76	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.031	0.12	-9999	-0.35	10	10
EGFR	-0.014	0.15	-9999	-0.8	10	10
PLCG1	-0.01	0.074	-9999	-0.38	4	4
PLD2	-0.021	0.12	-9999	-0.76	1	1
G12/G13	-0.059	0.12	-9999	-0.67	3	3
PI3K-beta	-0.04	0.083	-9999	-0.59	2	2
cell migration	-0.012	0.045	-9999	-10000	0	0
SLC9A3R2	0.011	0.047	-9999	-0.8	1	1
PXN	-0.005	0.094	-9999	-0.44	1	1
HRAS/GTP	-0.009	0.12	-9999	-0.47	7	7
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.61	0.35	-9999	-0.8	230	230
PRKCE	0.013	0.001	-9999	-10000	0	0
PRKCD	0.016	0.068	-9999	-0.46	1	1
Gi(beta/gamma)	-0.012	0.12	-9999	-0.45	9	9
mol:LPA	-0.037	0.082	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.033	0.086	-9999	-0.6	1	1
MAPKKK cascade	-0.008	0.12	-9999	-0.46	7	7
contractile ring contraction involved in cytokinesis	0.003	0.063	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.057	0.14	-9999	-0.34	53	53
GNA15	0.001	0.055	-9999	-0.33	4	4
GNA12	0.008	0.066	-9999	-0.8	2	2
GNA13	0.013	0	-9999	-10000	0	0
MAPT	-0.14	0.18	-9999	-0.46	24	24
GNA11	0.001	0.055	-9999	-0.33	4	4
Rac1/GTP	-0.004	0.096	-9999	-0.96	3	3
MMP2	-0.13	0.32	-9999	-0.72	66	66

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.013	0	-9999	-10000	0	0
EGFR	-0.014	0.15	-9999	-0.8	10	10
EGF/EGFR	-0.091	0.16	-9999	-0.49	11	11
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.089	0.15	-9999	-0.48	10	10
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.011	0.038	-9999	-0.64	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.14	0.27	-9999	-0.64	69	69
EGF/EGFR dimer/SHC	-0.11	0.18	-9999	-0.42	78	78
mol:GDP	-0.088	0.15	-9999	-0.47	10	10
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.007	0.065	-9999	-0.64	3	3
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.08	0.14	-9999	-0.72	1	1
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.081	0.14	-9999	-0.72	1	1
FRAP1	-0.054	0.16	-9999	-0.46	10	10
EGF/EGFR dimer	-0.13	0.22	-9999	-0.49	78	78
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.006	0.054	-9999	-0.47	4	4

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.17	0.3	-9999	-0.65	85	85
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.013	0	-9999	-10000	0	0
TCEB1	0.011	0.047	-9999	-0.8	1	1
HIF1A/p53	0.022	0.047	-9999	-0.3	3	3
HIF1A	0.018	0.035	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.026	-9999	-10000	0	0
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.31	0.39	-9999	-0.77	124	124
ARNT/IPAS	-0.13	0.22	-9999	-0.48	85	85
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.025	0.034	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.002	0.03	-9999	-0.53	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.025	0.034	-9999	-10000	0	0
PHD1-3/OS9	-0.036	0.13	-9999	-0.48	22	22
HIF1A/RACK1/Elongin B/Elongin C	-0.007	0.029	-9999	-0.38	1	1
VHL	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.025	0.034	-9999	-10000	0	0
EGLN3	-0.048	0.22	-9999	-0.8	23	23
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.013	0	-9999	-10000	0	0
TP53	0.007	0.065	-9999	-0.64	3	3
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.037	0.018	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.15	0.22	-9999	-0.43	100	100

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.046	0.16	0.62	22	-10000	0	22
KIRREL	0.006	0.042	-10000	0	-0.64	1	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.047	0.16	-10000	0	-0.62	22	22
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.046	0.16	-10000	0	-0.55	25	25
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.002	0.1	-10000	0	-0.56	5	5
FYN	-0.025	0.15	-10000	0	-0.49	26	26
mol:Ca2+	-0.046	0.16	-10000	0	-0.54	25	25
mol:DAG	-0.046	0.16	-10000	0	-0.54	25	25
NPHS2	-0.025	0.14	-10000	0	-0.84	9	9
mol:IP3	-0.046	0.16	-10000	0	-0.54	25	25
regulation of endocytosis	-0.04	0.14	-10000	0	-0.78	5	5
Nephrin/NEPH1/podocin/Cholesterol	-0.047	0.16	-10000	0	-0.55	25	25
establishment of cell polarity	-0.046	0.16	-10000	0	-0.62	22	22
Nephrin/NEPH1/podocin/NCK1-2	-0.042	0.15	-10000	0	-0.85	5	5
Nephrin/NEPH1/beta Arrestin2	-0.041	0.14	-10000	0	-0.8	5	5
NPHS1	-0.05	0.21	-10000	0	-0.81	21	21
Nephrin/NEPH1/podocin	-0.044	0.15	-10000	0	-0.5	26	26
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.046	0.16	-10000	0	-0.55	25	25
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.046	0.16	-10000	0	-0.55	25	25
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.063	0.21	-10000	0	-0.53	44	44
cytoskeleton organization	0	0.14	-10000	0	-0.75	5	5
Nephrin/NEPH1	-0.035	0.12	-10000	0	-0.47	22	22
Nephrin/NEPH1/ZO-1	-0.038	0.13	-10000	0	-0.52	21	21

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.02	0.006	-9999	-10000	0	0
RAS family/GTP	-0.054	0.098	-9999	-0.63	1	1
NFATC4	-0.026	0.13	-9999	-0.5	2	2
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.074	0.14	-9999	-0.62	1	1
JUN	0.005	0.075	-9999	-0.28	1	1
HRAS	0.013	0.001	-9999	-10000	0	0
DOCK7	-0.045	0.15	-9999	-0.59	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.099	0.19	-9999	-0.46	61	61
AKT1	0.011	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.045	0.081	-9999	-0.36	4	4
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.057	0.17	-9999	-0.7	1	1
RAF1	-0.024	0.12	-9999	-0.61	1	1
ErbB2/ErbB3/neuregulin 2	-0.23	0.18	-9999	-0.38	188	188
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.002	0.091	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.003	-9999	-10000	0	0
cell proliferation	-0.15	0.28	-9999	-0.6	51	51
FOS	-0.12	0.24	-9999	-0.51	49	49
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.074	0.14	-9999	-0.62	1	1
MAPK3	-0.11	0.23	-9999	-0.58	14	14
MAPK1	-0.11	0.23	-9999	-0.58	14	14
JAK2	-0.045	0.15	-9999	-0.59	1	1
NF2	-0.003	0.005	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.038	0.13	-9999	-0.7	1	1
NRG1	-0.15	0.32	-9999	-0.8	61	61
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.024	0.11	-9999	-0.43	1	1
MAPK9	-0.035	0.067	-9999	-10000	0	0
ERBB2	-0.004	0.051	-9999	-0.63	2	2
ERBB3	0.001	0.075	-9999	-0.64	4	4
SHC1	0.012	0.003	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.011	0.011	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.003	-9999	-10000	0	0
RNF41	0.026	0.009	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.05	0.095	-9999	-0.39	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.004	0.043	-9999	-0.54	2	2
CHRNA1	-0.16	0.29	-9999	-0.63	59	59
myelination	-0.017	0.13	-9999	-0.46	2	2
PPP3CB	-0.042	0.14	-9999	-0.54	1	1
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.05	0.099	-9999	-0.61	1	1
NRG2	-0.38	0.32	-9999	-0.64	184	184
mol:GDP	-0.038	0.13	-9999	-0.69	1	1
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.029	0.13	-9999	-0.59	1	1
SRC	0.013	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.046	0.15	-9999	-0.58	1	1
MAP2K1	-0.097	0.2	-9999	-0.53	14	14
heart morphogenesis	-0.074	0.14	-9999	-0.62	1	1
RAS family/GDP	-0.049	0.097	-9999	-0.61	1	1
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.005	0.009	-9999	-10000	0	0
CHRNE	0.012	0.022	-9999	-0.22	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.011	0.003	-9999	-10000	0	0
nervous system development	-0.074	0.14	-9999	-0.62	1	1
CDC42	0.013	0	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	0.003	0.083	-9999	-0.64	5	5
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.088	0.18	-9999	-0.42	63	63
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.05	0.17	-9999	-0.56	8	8
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.022	0.16	-9999	-0.8	12	12
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.34	0.4	-9999	-0.8	132	132
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.016	0.098	-9999	-0.61	8	8
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.011	0.047	-9999	-0.8	1	1
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.095	0.27	-9999	-0.8	39	39
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.1	0.19	-9999	-0.44	70	70
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.043	0.17	-9999	-0.59	9	9
MAP1B	-0.01	0.054	-9999	-0.3	10	10
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.029	0.16	-9999	-0.72	2	2
RELN	-0.11	0.26	-9999	-0.64	57	57
PAFAH/LIS1	-0.21	0.28	-9999	-0.53	132	132
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.064	0.11	-9999	-0.55	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.031	0.14	-9999	-0.61	4	4
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.054	0.18	-9999	-0.64	9	9
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.025	0	-9999	-10000	0	0
PAFAH1B3	0.013	0	-9999	-10000	0	0
PAFAH1B2	0.013	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.02	0.039	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.081	0.13	-9999	-0.56	9	9
LRP8	-0.008	0.13	-9999	-0.8	8	8
NDEL1/Katanin 60	-0.043	0.17	-9999	-0.59	9	9
P39/CDK5	-0.09	0.22	-9999	-0.82	9	9
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.037	0.16	-9999	-0.52	8	8
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.085	0.16	-9999	-0.56	12	12
RELN/VLDLR	-0.085	0.16	-9999	-0.56	8	8
CDC42	0	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.065	0.2	-10000	0	-0.88	8	8
NCK1/PAK1/Dok-R	-0.022	0.076	-10000	0	-0.42	8	8
NCK1/Dok-R	-0.035	0.19	-10000	0	-1.1	8	8
PIK3CA	0.012	0.004	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.007	0.036	0.24	5	-10000	0	5
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0.004	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.072	0.23	-10000	0	-0.83	26	26
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.031	0.17	-10000	0	-1	8	8
FN1	-0.44	0.4	-10000	0	-0.8	170	170
PLD2	0.048	0.21	-10000	0	-1.2	8	8
PTPN11	0.013	0	-10000	0	-10000	0	0
GRB14	-0.058	0.21	-10000	0	-0.66	32	32
ELK1	0.061	0.19	-10000	0	-1	8	8
GRB7	0.003	0.089	-10000	0	-0.76	4	4
PAK1	0.011	0.047	-10000	0	-0.8	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.37	0.34	-10000	0	-0.83	86	86
CDKN1A	0.067	0.18	-10000	0	-0.66	3	3
ITGA5	-0.27	0.39	-10000	0	-0.8	105	105
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.035	0.19	-10000	0	-1.1	8	8
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.068	0.16	-10000	0	-0.64	8	8
PLG	0.042	0.21	-10000	0	-1.2	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.048	0.18	-10000	0	-0.86	8	8
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0.004	-10000	0	-10000	0	0
ANGPT2	0.014	0.2	-10000	0	-0.61	18	18
BMX	0.013	0.25	-10000	0	-1.3	8	8
ANGPT1	0.022	0.21	-10000	0	-1.2	7	7
tube development	0.06	0.19	-10000	0	-0.72	5	5
ANGPT4	0.009	0.007	-10000	0	-10000	0	0
response to hypoxia	0.003	0.013	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.004	0.24	-10000	0	-1.2	8	8
alpha5/beta1 Integrin	-0.22	0.29	-10000	0	-0.61	106	106
FGF2	-0.013	0.13	-10000	0	-0.68	11	11
STAT5A (dimer)	0.064	0.21	-10000	0	-0.86	3	3
mol:L-citrulline	0.068	0.16	-10000	0	-0.64	8	8
AGTR1	-0.047	0.19	-10000	0	-0.66	27	27
MAPK14	0.051	0.21	-10000	0	-1.1	8	8
Tie2/SHP2	-0.017	0.12	-10000	0	-1.2	3	3
TEK	0.03	0.15	-10000	0	-1.4	3	3
RPS6KB1	0.069	0.19	-10000	0	-0.85	8	8
Angiotensin II/AT1	-0.035	0.14	-10000	0	-0.5	27	27
Tie2/Ang1/GRB2	0.044	0.22	-10000	0	-1.2	8	8
MAPK3	0.056	0.19	-10000	0	-1	8	8
MAPK1	0.056	0.19	-10000	0	-1	8	8
Tie2/Ang1/GRB7	0.038	0.22	-10000	0	-1.2	8	8
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.046	0.22	-10000	0	-1.2	8	8
PI3K	0.06	0.21	-10000	0	-1	8	8
FES	0.051	0.21	-10000	0	-1.1	8	8
Crk/Dok-R	-0.035	0.19	-10000	0	-1.1	8	8
Tie2/Ang1/ABIN2	0.044	0.22	-10000	0	-1.2	8	8
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.067	0.18	-10000	0	-0.78	8	8
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.069	0.19	-10000	0	-0.85	8	8
Tie2/Ang2	0.048	0.23	-10000	0	-0.99	4	4
Tie2/Ang1	0.042	0.23	-10000	0	-1.3	8	8
FOXO1	0.068	0.19	-10000	0	-0.79	8	8
ELF1	0.023	0.011	-10000	0	-10000	0	0
ELF2	0.045	0.21	-10000	0	-1.1	8	8
mol:Choline	0.05	0.2	-10000	0	-1.1	8	8
cell migration	-0.1	0.084	-10000	0	-10000	0	0
FYN	0.057	0.21	-10000	0	-0.82	5	5
DOK2	0.011	0.038	-10000	0	-0.64	1	1
negative regulation of cell cycle	0.068	0.17	-10000	0	-0.59	3	3
ETS1	0.015	0.073	-10000	0	-0.78	2	2
PXN	0.077	0.16	-10000	0	-0.69	8	8
ITGB1	0.011	0.047	-10000	0	-0.8	1	1
NOS3	0.067	0.18	-10000	0	-0.74	8	8
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.017	0.17	-10000	0	-0.76	15	15
MAPKKK cascade	0.05	0.2	-10000	0	-1.1	8	8
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.045	0.22	-10000	0	-1.2	8	8
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.069	0.15	-10000	0	-0.58	8	8
mol:Phosphatidic acid	0.05	0.2	-10000	0	-1.1	8	8
mol:Angiotensin II	0	0.007	-10000	0	-10000	0	0
mol:NADP	0.068	0.16	-10000	0	-0.64	8	8
Rac1/GTP	-0.038	0.14	-10000	0	-0.79	8	8
MMP2	-0.047	0.28	-10000	0	-1.2	8	8

×

Regulation of Androgen receptor activity

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
HDAC1	0.023	0.004	-9999	-10000	0	0
SMARCC1	0.01	0.011	-9999	-10000	0	0
REL	0.016	0.007	-9999	-10000	0	0
HDAC7	-0.061	0.17	-9999	-0.63	11	11
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.013	0.001	-9999	-10000	0	0
KAT2B	-0.016	0.13	-9999	-0.64	13	13
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.009	0.11	-9999	-0.5	14	14
FOXO1	0.013	0.001	-9999	-10000	0	0
T-DHT/AR	-0.077	0.17	-9999	-0.64	14	14
MAP2K6	-0.023	0.14	-9999	-0.66	14	14
BRM/BAF57	-0.001	0.002	-9999	-10000	0	0
MAP2K4	0.008	0.008	-9999	-10000	0	0
SMARCA2	0.011	0.005	-9999	-10000	0	0
PDE9A	-0.093	0.21	-9999	-1.3	8	8
NCOA2	0.004	0.075	-9999	-0.64	4	4
CEBPA	0.01	0.053	-9999	-0.64	2	2
EHMT2	0.011	0.005	-9999	-10000	0	0
cell proliferation	-0.048	0.16	-9999	-0.51	9	9
NR0B1	-0.038	0.18	-9999	-0.8	16	16
EGR1	-0.013	0.12	-9999	-0.64	11	11
RXRs/9cRA	-0.053	0.13	-9999	-0.38	42	42
AR/RACK1/Src	-0.029	0.12	-9999	-0.52	10	10
AR/GR	-0.044	0.15	-9999	-0.59	10	10
GNB2L1	0.013	0.003	-9999	-10000	0	0
PKN1	0.007	0.066	-9999	-0.8	2	2
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.011	0.045	-9999	-0.5	2	2
T-DHT/AR/TIF2/CARM1	-0.028	0.14	-9999	-0.57	12	12
SRC	0	0.096	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.31	0.47	-9999	-1.2	58	58
APPBP2	0.008	0.008	-9999	-10000	0	0
TRIM24	0.009	0.038	-9999	-0.64	1	1
T-DHT/AR/TIP60	-0.029	0.13	-9999	-0.55	11	11
TMPRSS2	-0.54	0.57	-9999	-1.1	145	145
RXRG	-0.082	0.23	-9999	-0.66	42	42
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	0.013	0.003	-9999	-10000	0	0
NR2C2	0.011	0.038	-9999	-0.64	1	1
KLK2	-0.022	0.17	-9999	-0.65	13	13
AR	-0.058	0.17	-9999	-0.43	36	36
SENP1	0.013	0.001	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.018	0.012	-9999	-10000	0	0
SRY	-0.043	0.18	-9999	-0.65	25	25
GATA2	0.008	0.066	-9999	-0.8	2	2
MYST2	0.014	0.001	-9999	-10000	0	0
HOXB13	-0.28	0.39	-9999	-0.81	105	105
T-DHT/AR/RACK1/Src	-0.02	0.13	-9999	-0.53	10	10
positive regulation of transcription	0.008	0.066	-9999	-0.8	2	2
DNAJA1	0.008	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.004	-9999	-10000	0	0
NCOA1	0.017	0.008	-9999	-10000	0	0
SPDEF	-0.24	0.32	-9999	-0.65	117	117
T-DHT/AR/TIF2	-0.01	0.11	-9999	-0.53	4	4
T-DHT/AR/Hsp90	-0.03	0.13	-9999	-0.56	10	10
GSK3B	0.008	0.007	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.011	0.1	-9999	-0.43	6	6
SIRT1	0.013	0.001	-9999	-10000	0	0
ZMIZ2	0.018	0.012	-9999	-10000	0	0
POU2F1	0.017	0.017	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.073	0.15	-9999	-0.54	19	19
CREBBP	0.013	0.003	-9999	-10000	0	0
SMARCE1	0.011	0.005	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.02	0.092	-9999	-0.44	14	14
EFNA5	-0.01	0.12	-9999	-0.64	11	11
FYN	0.003	0.1	-9999	-0.42	14	14
neuron projection morphogenesis	-0.02	0.092	-9999	-0.44	14	14
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.02	0.092	-9999	-0.44	14	14
EPHA5	0	0.081	-9999	-0.8	3	3

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.009	0.061	-9999	-0.4	7	7
ARNO/beta Arrestin1-2	-0.025	0.088	-9999	-0.58	2	2
EGFR	-0.014	0.15	-9999	-0.8	10	10
EPHA2	0.005	0.075	-9999	-0.64	4	4
USP6	0.013	0	-9999	-10000	0	0
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.13	0.22	-9999	-0.49	78	78
ARRB2	0.011	0.003	-9999	-10000	0	0
mol:GTP	0.021	0.018	-9999	-10000	0	0
ARRB1	0.009	0.053	-9999	-0.64	2	2
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	-0.005	0.11	-9999	-0.8	6	6
EGF	-0.14	0.27	-9999	-0.64	69	69
somatostatin receptor activity	0	0	-9999	-0.001	7	7
ARAP2	0.009	0.053	-9999	-0.64	2	2
mol:GDP	-0.011	0.076	-9999	-0.33	6	6
mol:PI-3-4-5-P3	0	0	-9999	-0.001	5	5
ITGA2B	-0.04	0.2	-9999	-0.8	20	20
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.049	-9999	-0.48	1	1
ADAP1	0.013	0	-9999	-10000	0	0
KIF13B	-0.002	0.098	-9999	-0.64	7	7
HGF/MET	-0.019	0.099	-9999	-0.52	11	11
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.028	0.11	-9999	-0.34	7	7
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.11	0.18	-9999	-0.42	78	78
ADRB2	-0.038	0.18	-9999	-0.64	24	24
receptor agonist activity	0	0	-9999	0	7	7
actin filament binding	0	0	-9999	-0.001	6	6
SRC	0.013	0	-9999	-10000	0	0
ITGB3	-0.017	0.15	-9999	-0.76	12	12
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	5	5
ARF6/GDP	0.044	0.057	-9999	-10000	0	0
ARF6/GDP/GULP/ACAP1	-0.11	0.17	-9999	-0.47	23	23
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.049	0.15	-9999	-0.5	28	28
ACAP1	-0.003	0.11	-9999	-0.8	6	6
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0	0	-9999	-10000	0	0
EFNA1	0.011	0.047	-9999	-0.8	1	1
HGF	-0.008	0.12	-9999	-0.7	9	9
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	-0.001	6	6
endosomal lumen acidification	0	0	-9999	-0.001	7	7
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.16	0.29	-9999	-0.64	81	81
GNAQ/ARNO	0.014	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	-10000	0	0
MET	0.009	0.06	-9999	-0.72	2	2
GNA14	-0.095	0.24	-9999	-0.64	50	50
GNA15	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	5	5
GNA11	0.013	0	-9999	-10000	0	0
LHCGR	0.002	0.005	-9999	-10000	0	0
AGTR1	-0.048	0.19	-9999	-0.66	27	27
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-9999	-10000	0	0
IPCEF1/ARNO	-0.078	0.15	-9999	-0.44	10	10
alphaIIb/beta3 Integrin	-0.063	0.19	-9999	-0.62	31	31

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.007	0.11	-9999	-0.69	7	7
PDGF/PDGFRA/CRKL	-0.014	0.083	-9999	-0.52	8	8
positive regulation of JUN kinase activity	-0.009	0.056	-9999	-0.45	2	2
CRKL	0.011	0.047	-9999	-0.8	1	1
PDGF/PDGFRA/Caveolin-3	-0.12	0.22	-9999	-0.5	75	75
AP1	-0.17	0.37	-9999	-1	49	49
mol:IP3	0.006	0.084	-9999	-0.52	7	7
PLCG1	0.006	0.084	-9999	-0.52	7	7
PDGF/PDGFRA/alphaV Integrin	-0.017	0.1	-9999	-0.63	8	8
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	0.006	0.084	-9999	-0.51	7	7
CAV3	-0.14	0.28	-9999	-0.66	69	69
CAV1	-0.065	0.24	-9999	-0.8	29	29
SHC/Grb2/SOS1	-0.009	0.056	-9999	-0.45	2	2
PDGF/PDGFRA/Shf	-0.022	0.11	-9999	-0.56	12	12
FOS	-0.12	0.39	-9999	-0.99	49	49
JUN	-0.01	0.022	-9999	-10000	0	0
oligodendrocyte development	-0.017	0.1	-9999	-0.63	8	8
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	0.006	0.084	-9999	-0.52	7	7
PDGF/PDGFRA	-0.007	0.11	-9999	-0.69	7	7
actin cytoskeleton reorganization	-0.015	0.084	-9999	-0.49	9	9
SRF	0.026	0.01	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.01	0.063	-9999	-0.42	7	7
PDGF/PDGFRA/Crk/C3G	-0.01	0.063	-9999	-0.47	3	3
JAK1	0.01	0.079	-9999	-0.5	7	7
ELK1/SRF	0.03	0.068	-9999	-0.49	1	1
SHB	0.009	0.053	-9999	-0.64	2	2
SHF	-0.002	0.098	-9999	-0.64	7	7
CSNK2A1	0.01	0.022	-9999	-10000	0	0
GO:0007205	0.006	0.085	-9999	-0.52	7	7
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.009	0.056	-9999	-0.45	2	2
PDGF/PDGFRA/SHB	-0.015	0.084	-9999	-0.49	9	9
PDGF/PDGFRA/Caveolin-1	-0.072	0.2	-9999	-0.6	36	36
ITGAV	0.006	0.076	-9999	-0.75	3	3
ELK1	0.008	0.089	-9999	-0.47	8	8
PIK3CA	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.012	0.076	-9999	-0.5	7	7
JAK-STAT cascade	0.01	0.079	-9999	-0.5	7	7
cell proliferation	-0.022	0.11	-9999	-0.56	12	12

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.028	0.14	-9999	-0.65	5	5
FZD6	0.013	0	-9999	-10000	0	0
WNT6	-0.03	0.18	-9999	-0.76	17	17
WNT4	-0.01	0.13	-9999	-0.69	10	10
FZD3	0.005	0.075	-9999	-0.64	4	4
WNT5A	0.004	0.08	-9999	-0.68	4	4
WNT11	-0.074	0.25	-9999	-0.76	34	34

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.14	0.29	-9999	-0.67	66	66
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.076	0.17	-9999	-0.47	49	49
IFNAR2	0.012	0.007	-9999	-10000	0	0
AKT1	-0.002	0.071	-9999	-0.36	2	2
ER alpha/Oestrogen	-0.032	0.13	-9999	-0.58	17	17
NFX1/SIN3/HDAC complex	0.041	0.023	-9999	-10000	0	0
EGF	-0.14	0.27	-9999	-0.64	69	69
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.015	0.012	-9999	-10000	0	0
TERT/c-Abl	-0.15	0.26	-9999	-0.62	66	66
SAP18	0.011	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.18	0.34	-9999	-0.8	71	71
WRN	0.013	0	-9999	-10000	0	0
SP1	0.013	0.007	-9999	-10000	0	0
SP3	0.011	0.006	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.14	0.23	-9999	-0.64	29	29
Mad/Max	-0.002	0.027	-9999	-0.47	1	1
TERT	-0.15	0.3	-9999	-0.68	66	66
CCND1	-0.13	0.29	-9999	-0.73	32	32
MAX	0.011	0.006	-9999	-10000	0	0
RBBP7	0.011	0.006	-9999	-10000	0	0
RBBP4	0.011	0.006	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.011	0.006	-9999	-10000	0	0
Telomerase/911	0.022	0.044	-9999	-10000	0	0
CDKN1B	-0.072	0.22	-9999	-0.51	59	59
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.011	0.006	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.011	0.006	-9999	-10000	0	0
JUN	0.012	0.006	-9999	-10000	0	0
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.006	-9999	-10000	0	0
FOS	-0.094	0.24	-9999	-0.64	49	49
IFN-gamma/IRF1	-0.12	0.24	-9999	-0.6	59	59
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.011	0.047	-9999	-0.8	1	1
Telomerase	0.002	0.086	-9999	-0.4	4	4
IRF1	0.015	0.008	-9999	-10000	0	0
ESR1	-0.031	0.18	-9999	-0.75	17	17
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.045	0.025	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.046	0.025	-9999	-10000	0	0
HDAC1	0.011	0.006	-9999	-10000	0	0
HDAC2	0.013	0.007	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.023	0.047	-9999	-0.54	2	2
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.009	0.038	-9999	-0.64	1	1
MRE11A	0.013	0	-9999	-10000	0	0
HUS1	0.011	0.047	-9999	-0.8	1	1
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.25	-9999	-0.64	48	48
NR2F2	0.016	0.01	-9999	-10000	0	0
MAPK3	0.012	0.039	-9999	-0.64	1	1
MAPK1	0.012	0.039	-9999	-0.64	1	1
TGFB1/TGF beta receptor Type II	0.011	0.047	-9999	-0.8	1	1
NFKB1	0.013	0	-9999	-10000	0	0
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.013	0	-9999	-10000	0	0
EGFR	-0.015	0.15	-9999	-0.81	10	10
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.13	0.22	-9999	-0.5	78	78
MYC	0.011	0.006	-9999	-10000	0	0
IL2	0	0.05	-9999	-0.84	1	1
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.011	0.047	-9999	-0.8	1	1
TRF2/BLM	-0.002	0.033	-9999	-0.57	1	1
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.15	0.26	-9999	-0.66	48	48
SP1/HDAC2	0.019	0.014	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.14	0.23	-9999	-0.64	29	29
Smad3/Myc	0.018	0.042	-9999	-0.46	2	2
911 complex	-0.002	0.03	-9999	-0.53	1	1
IFNG	-0.14	0.32	-9999	-0.8	59	59
Telomerase/PinX1	-0.14	0.23	-9999	-0.64	29	29
Telomerase/AKT1/mTOR/p70S6K	-0.001	0.08	-9999	-0.48	1	1
SIN3B	0.011	0.006	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.14	0.23	-9999	-0.64	29	29
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.23	-9999	-0.64	29	29
E2F1	-0.034	0.19	-9999	-0.81	17	17
ZNFX1	0.011	0.006	-9999	-10000	0	0
PIF1	-0.014	0.15	-9999	-0.8	10	10
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.013	0	-9999	-10000	0	0
LAT2	-0.05	0.13	-9999	-0.44	9	9
AP1	-0.1	0.13	-9999	-0.44	25	25
mol:PIP3	-0.073	0.19	-9999	-0.54	12	12
IKBKB	-0.027	0.12	-9999	-0.38	2	2
AKT1	-0.06	0.17	-9999	-0.59	6	6
IKBKG	-0.027	0.12	-9999	-0.38	2	2
MS4A2	-0.01	0.12	-9999	-0.7	9	9
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
MAP3K1	-0.013	0.12	-9999	-0.44	2	2
mol:Ca2+	-0.052	0.15	-9999	-0.39	12	12
LYN	0.014	0.004	-9999	-10000	0	0
CBLB	-0.049	0.13	-9999	-0.46	7	7
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.03	0.099	-9999	-10000	0	0
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.011	0.038	-9999	-0.64	1	1
PLD2	-0.099	0.19	-9999	-0.6	10	10
PTPN13	-0.042	0.13	-9999	-0.48	4	4
PTPN11	0.01	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.024	0.14	-9999	-0.36	4	4
SYK	0.011	0.038	-9999	-0.65	1	1
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.16	-9999	-0.57	12	12
LAT	-0.061	0.15	-9999	-0.51	14	14
PAK2	-0.024	0.12	-9999	-0.44	6	6
NFATC2	-0.087	0.18	-9999	-0.71	19	19
HRAS	-0.035	0.13	-9999	-0.45	9	9
GAB2	0.009	0.053	-9999	-0.64	2	2
PLA2G1B	0.036	0.019	-9999	-10000	0	0
Fc epsilon R1	-0.16	0.22	-9999	-0.43	112	112
Antigen/IgE/Fc epsilon R1	-0.15	0.2	-9999	-0.39	112	112
mol:GDP	-0.042	0.14	-9999	-0.47	9	9
JUN	0.013	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.092	0.24	-9999	-0.64	49	49
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.086	0.12	-9999	-0.46	9	9
CHUK	-0.027	0.12	-9999	-0.38	2	2
KLRG1	-0.057	0.14	-9999	-0.49	9	9
VAV1	-0.055	0.14	-9999	-0.51	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.049	0.13	-9999	-0.44	9	9
negative regulation of mast cell degranulation	-0.047	0.13	-9999	-0.45	9	9
BTK	-0.076	0.11	-9999	-0.45	7	7
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.087	0.18	-9999	-0.66	10	10
GAB2/PI3K/SHP2	-0.11	0.15	-9999	-0.65	6	6
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.071	0.15	-9999	-0.63	6	6
RAF1	0.024	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.14	0.19	-9999	-0.64	14	14
FCER1G	-0.002	0.1	-9999	-0.81	5	5
FCER1A	-0.22	0.32	-9999	-0.65	106	106
Antigen/IgE/Fc epsilon R1/Fyn	-0.14	0.19	-9999	-0.64	10	10
MAPK3	0.035	0.02	-9999	-10000	0	0
MAPK1	0.035	0.02	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.006	0.065	-9999	-0.6	2	2
DUSP1	-0.041	0.18	-9999	-0.64	25	25
NF-kappa-B/RelA	-0.039	0.049	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.048	0.13	-9999	-0.45	6	6
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.068	0.099	-9999	-0.47	6	6
FER	-0.049	0.13	-9999	-0.44	9	9
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.035	0.085	-9999	-0.42	12	12
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.042	0.14	-9999	-0.48	9	9
cytokine secretion	-0.028	0.036	-9999	-10000	0	0
SPHK1	-0.053	0.14	-9999	-0.49	10	10
PTK2	-0.05	0.13	-9999	-0.47	6	6
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.16	-9999	-0.58	9	9
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.063	0.18	-9999	-0.52	9	9
MAP2K2	0.031	0.02	-9999	-10000	0	0
MAP2K1	0.031	0.02	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.081	0.11	-9999	-0.47	9	9
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.15	0.2	-9999	-0.68	14	14
mol:Choline	-0.098	0.19	-9999	-0.59	10	10
SHC/Grb2/SOS1	-0.069	0.097	-9999	-0.45	4	4
FYN	0.011	0.047	-9999	-0.8	1	1
DOK1	0.013	0	-9999	-10000	0	0
PXN	-0.039	0.12	-9999	-0.48	3	3
HCLS1	-0.053	0.14	-9999	-0.48	10	10
PRKCB	-0.051	0.15	-9999	-0.4	11	11
FCGR2B	0	0.091	-9999	-0.64	6	6
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.047	0.13	-9999	-0.46	9	9
LCP2	0.005	0.081	-9999	-0.8	3	3
PLA2G4A	-0.063	0.16	-9999	-0.52	17	17
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.098	0.19	-9999	-0.59	10	10
IKK complex	-0.004	0.095	-9999	-0.28	1	1
WIPF1	0.003	0.093	-9999	-0.8	4	4

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.005	0.081	-10000	0	-0.8	3	3
ANTXR2	-0.008	0.13	-10000	0	-0.8	8	8
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.018	-10000	0	-0.096	11	11
monocyte activation	-0.032	0.12	-10000	0	-0.28	49	49
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.003	0.015	-10000	0	-10000	0	0
MAP2K7	-0.003	0.015	-10000	0	-10000	0	0
MAP2K6	-0.019	0.075	-10000	0	-0.36	14	14
CYAA	-0.001	0.091	-10000	0	-0.47	11	11
MAP2K4	-0.003	0.015	-10000	0	-10000	0	0
IL1B	-0.029	0.14	-10000	0	-0.45	30	30
Channel	-0.018	0.093	-10000	0	-0.5	11	11
NLRP1	-0.004	0.031	-10000	0	-0.48	1	1
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.004	0.022	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.018	0.096	11	-10000	0	11
MAPK3	-0.003	0.015	-10000	0	-10000	0	0
MAPK1	-0.003	0.015	-10000	0	-10000	0	0
PGR	-0.049	0.12	-10000	0	-0.38	37	37
PA/Cellular Receptors	-0.019	0.1	-10000	0	-0.54	11	11
apoptosis	-0.003	0.018	-10000	0	-0.096	11	11
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0	0.087	-10000	0	-0.45	11	11
macrophage activation	0.019	0.017	-10000	0	-10000	0	0
TNF	-0.025	0.17	-10000	0	-0.76	15	15
VCAM1	-0.032	0.12	-10000	0	-0.28	49	49
platelet activation	-0.004	0.022	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.026	-10000	0	-10000	0	0
IL18	0.004	0.069	-10000	0	-0.35	10	10
negative regulation of macrophage activation	-0.003	0.018	-10000	0	-0.096	11	11
LEF	-0.004	0.018	-10000	0	-0.097	11	11
CASP1	-0.004	0.02	-10000	0	-0.22	1	1
mol:cAMP	-0.004	0.022	-10000	0	-10000	0	0
necrosis	-0.003	0.018	-10000	0	-0.096	11	11
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.017	0.088	-10000	0	-0.47	11	11
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0.094	-9999	-0.47	10	10
CRKL	0.011	0.047	-9999	-0.8	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.013	0	-9999	-10000	0	0
ITGA4	-0.014	0.15	-9999	-0.8	10	10
alpha4/beta7 Integrin/MAdCAM1	-0.038	0.13	-9999	-0.48	23	23
EPO	-0.056	0.22	-9999	-0.8	25	25
alpha4/beta7 Integrin	-0.022	0.11	-9999	-0.6	11	11
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.61	11	11
EPO/EPOR (dimer)	-0.065	0.19	-9999	-0.61	32	32
lamellipodium assembly	0.002	0.015	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
JAK2	-0.039	0.11	-9999	-0.59	2	2
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.025	0.16	-9999	-0.8	13	13
cell adhesion	-0.037	0.13	-9999	-0.48	23	23
CRKL/CBL	-0.002	0.035	-9999	-0.61	1	1
ITGB1	0.011	0.047	-9999	-0.8	1	1
SRC	-0.039	0.19	-9999	-0.5	39	39
ITGB7	0.011	0.038	-9999	-0.64	1	1
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.078	0.19	-9999	-0.55	39	39
p130Cas/Crk/Dock1	-0.058	0.14	-9999	-0.79	2	2
VCAM1	-0.078	0.25	-9999	-0.78	35	35
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.017	0.09	-9999	-0.48	11	11
BCAR1	-0.027	0.18	-9999	-0.88	2	2
EPOR	-0.005	0.12	-9999	-0.8	7	7
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	0.002	0.015	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.14	0.61	16	-10000	0	16
CDKN1A	0.001	0.012	-10000	0	-10000	0	0
KAT2B	-0.015	0.13	-10000	0	-0.64	13	13
BAX	0.013	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.023	0.027	-10000	0	-0.31	2	2
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	0.005	0.047	-10000	0	-0.8	1	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.093	0.22	-10000	0	-0.5	66	66
PPARGC1A	-0.21	0.31	-10000	0	-0.64	102	102
FHL2	0.009	0.053	-10000	0	-0.64	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0	-10000	0	-10000	0	0
HIST2H4A	-0.012	0.14	-10000	0	-0.62	16	16
SIRT1/FOXO3a	0	0	-10000	0	-10000	0	0
SIRT1	0	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.007	0.04	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.14	0.19	-10000	0	-0.4	102	102
p53/SIRT1	-0.005	0.047	-10000	0	-0.47	3	3
SIRT1/FOXO4	-0.001	0.021	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.002	0.029	-10000	0	-10000	0	0
HIST1H1E	0.016	0.052	-10000	0	-0.28	9	9
SIRT1/p300	0	0	-10000	0	-10000	0	0
muscle cell differentiation	0.091	0.18	0.64	6	-10000	0	6
TP53	-0.006	0.064	-10000	0	-0.64	3	3
KU70/SIRT1/BAX	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.002	0.035	-10000	0	-0.61	1	1
ACSS2	0.022	0	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.091	0.18	-10000	0	-0.65	6	6

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.099	0.28	-9999	-0.71	47	47
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.04	0.12	-9999	-0.4	7	7
ATF2/c-Jun	-0.007	0.094	-9999	-10000	0	0
MAPK11	-0.04	0.12	-9999	-0.4	7	7
MITF	-0.041	0.16	-9999	-0.56	11	11
MAPKAPK5	-0.033	0.14	-9999	-0.49	7	7
KRT8	-0.1	0.22	-9999	-0.67	20	20
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.059	0.18	-9999	-0.65	7	7
CEBPB	-0.033	0.14	-9999	-0.49	7	7
SLC9A1	-0.033	0.14	-9999	-0.49	7	7
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.027	0.14	-9999	-0.48	7	7
p38alpha-beta/MNK1	-0.033	0.15	-9999	-0.53	7	7
JUN	-0.006	0.093	-9999	-10000	0	0
PPARGC1A	-0.17	0.27	-9999	-0.73	39	39
USF1	-0.033	0.14	-9999	-0.49	7	7
RAB5/GDP/GDI1	-0.049	0.084	-9999	-0.41	2	2
NOS2	-0.11	0.31	-9999	-0.78	46	46
DDIT3	-0.041	0.16	-9999	-0.53	10	10
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.016	0.12	-9999	-0.45	2	2
p38alpha-beta/HBP1	-0.033	0.15	-9999	-0.53	7	7
CREB1	-0.029	0.15	-9999	-0.48	7	7
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.02	0.13	-9999	-0.47	7	7
RPS6KA4	-0.033	0.14	-9999	-0.49	7	7
PLA2G4A	-0.037	0.15	-9999	-0.6	4	4
GDI1	-0.033	0.14	-9999	-0.49	7	7
TP53	-0.048	0.18	-9999	-0.64	9	9
RPS6KA5	-0.034	0.15	-9999	-0.49	7	7
ESR1	-0.055	0.18	-9999	-0.57	14	14
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.041	0.16	-9999	-0.54	9	9
MEF2A	-0.033	0.14	-9999	-0.49	7	7
EIF4EBP1	-0.03	0.15	-9999	-0.48	7	7
KRT19	-0.16	0.23	-9999	-0.7	22	22
ELK4	-0.033	0.14	-9999	-0.49	7	7
ATF6	-0.033	0.14	-9999	-0.49	7	7
ATF1	-0.029	0.15	-9999	-0.48	7	7
p38alpha-beta/MAPKAPK2	-0.033	0.15	-9999	-0.53	7	7
p38alpha-beta/MAPKAPK3	-0.033	0.15	-9999	-0.53	7	7

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.028	0.16	-9999	-0.65	19	19
GNB1/GNG2	-0.052	0.11	-9999	-0.55	6	6
mol:DAG	-0.001	0.12	-9999	-0.52	5	5
PLCG1	-0.001	0.13	-9999	-0.54	5	5
YES1	-0.017	0.14	-9999	-0.61	5	5
FZD3	0.005	0.075	-9999	-0.64	4	4
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.049	0.1	-9999	-0.55	5	5
MAP3K7	-0.048	0.17	-9999	-0.49	15	15
mol:Ca2+	0	0.12	-9999	-0.5	5	5
mol:IP3	-0.001	0.12	-9999	-0.52	5	5
NLK	-0.005	0.008	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.06	0.18	-9999	-0.54	15	15
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.028	0.14	-9999	-0.65	5	5
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.017	0.14	-9999	-0.61	5	5
GO:0007205	0	0.12	-9999	-0.51	5	5
WNT6	-0.03	0.18	-9999	-0.76	17	17
WNT4	-0.01	0.13	-9999	-0.69	10	10
NFAT1/CK1 alpha	-0.063	0.13	-9999	-0.64	7	7
GNG2	0.011	0.047	-9999	-0.8	1	1
WNT5A	0.004	0.08	-9999	-0.68	4	4
WNT11	-0.074	0.25	-9999	-0.76	34	34
CDC42	-0.007	0.13	-9999	-0.57	5	5

×

Nectin adhesion 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
PDGFRB	-0.22	0.37	-9999	-0.8	85	85
alphaV beta3 Integrin	-0.028	0.13	-9999	-0.61	14	14
PTK2	-0.023	0.081	-9999	-0.71	1	1
positive regulation of JNK cascade	-0.009	0.041	-9999	-0.32	3	3
CDC42/GDP	0.044	0.069	-9999	-0.43	3	3
Rac1/GDP	0.046	0.069	-9999	-0.42	3	3
RAP1B	0.011	0.047	-9999	-0.8	1	1
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.011	0.038	-9999	-0.64	1	1
CDC42/GTP	-0.011	0.05	-9999	-0.39	3	3
nectin-3/I-afadin	-0.023	0.11	-9999	-0.58	12	12
RAPGEF1	0.043	0.075	-9999	-0.48	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.036	0.084	-9999	-0.56	3	3
PDGFB-D/PDGFRB	-0.22	0.37	-9999	-0.8	85	85
TLN1	0.025	0.057	-9999	-0.45	1	1
Rap1/GTP	-0.01	0.046	-9999	-0.39	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.002	0.028	-9999	-0.49	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.023	0.11	-9999	-0.58	12	12
PVR	0.011	0.047	-9999	-0.8	1	1
Necl-5(dimer)	0.011	0.047	-9999	-0.8	1	1
mol:GDP	0.043	0.081	-9999	-0.53	3	3
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	-0.14	0.21	-9999	-0.46	92	92
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.027	-9999	-0.47	1	1
positive regulation of lamellipodium assembly	-0.015	0.049	-9999	-0.33	3	3
PVRL1	0.011	0.038	-9999	-0.64	1	1
PVRL3	-0.017	0.15	-9999	-0.76	12	12
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.009	0.053	-9999	-0.64	2	2
CLDN1	-0.012	0.13	-9999	-0.7	11	11
JAM-A/CLDN1	-0.032	0.11	-9999	-0.48	13	13
SRC	-0.018	0.079	-9999	-0.63	3	3
ITGB3	-0.017	0.15	-9999	-0.76	12	12
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.027	-9999	-0.47	1	1
FARP2	0.04	0.078	-9999	-0.52	3	3
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.021	0.1	-9999	-0.5	13	13
nectin-1/I-afadin	-0.002	0.027	-9999	-0.47	1	1
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.021	0.1	-9999	-0.49	13	13
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.009	0.041	-9999	-0.32	3	3
alphaV/beta3 Integrin/Talin	0.017	0.11	-9999	-0.58	3	3
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0.019	0.053	-9999	-0.39	1	1
VAV2	0.029	0.091	-9999	-0.53	3	3
RAP1/GDP	-0.011	0.052	-9999	-0.46	1	1
ITGAV	0.006	0.076	-9999	-0.75	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.02	0.097	-9999	-0.5	12	12
nectin-3(dimer)/I-afadin/I-afadin	-0.023	0.11	-9999	-0.58	12	12
Rac1/GTP	-0.017	0.058	-9999	-0.41	3	3
PTPRM	-0.011	0.054	-9999	-0.43	1	1
E-cadherin/beta catenin/alpha catenin	-0.004	0.044	-9999	-0.64	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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
TNFSF10	-0.005	0.12	-10000	0	-0.78	7	7
positive regulation of NF-kappaB transcription factor activity	-0.037	0.14	-10000	0	-0.59	19	19
MAP2K4	0.011	0.099	-10000	0	-0.5	1	1
IKBKB	0.013	0	-10000	0	-10000	0	0
TNFRSF10B	0.013	0	-10000	0	-10000	0	0
TNFRSF10A	0.013	0	-10000	0	-10000	0	0
SMPD1	-0.006	0.037	-10000	0	-10000	0	0
IKBKG	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.018	0.15	-10000	0	-0.78	12	12
TRAIL/TRAILR2	-0.014	0.089	-10000	0	-0.59	7	7
TRAIL/TRAILR3	-0.027	0.12	-10000	0	-0.59	14	14
TRAIL/TRAILR1	-0.014	0.089	-10000	0	-0.59	7	7
TRAIL/TRAILR4	-0.037	0.14	-10000	0	-0.59	19	19
TRAIL/TRAILR1/DAP3/GTP	-0.011	0.071	-10000	0	-0.47	7	7
IKK complex	-0.025	0.062	-10000	0	-10000	0	0
RIPK1	0.013	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	0.011	0.093	-10000	0	-0.59	7	7
MAP3K1	-0.036	0.089	-10000	0	-0.54	1	1
TRAILR4 (trimer)	-0.018	0.15	-10000	0	-0.77	12	12
TRADD	0.013	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.013	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.003	0.11	-10000	0	-0.54	1	1
CFLAR	0.013	0	-10000	0	-10000	0	0
MAPK1	0.011	0.093	-10000	0	-0.59	7	7
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.063	0.16	-10000	0	-0.78	1	1
mol:ceramide	-0.006	0.037	-10000	0	-10000	0	0
FADD	-0.084	0.26	-10000	0	-0.8	36	36
MAPK8	0.017	0.1	-10000	0	-0.5	2	2
TRAF2	0.008	0.066	-10000	0	-0.8	2	2
TRAILR3 (trimer)	-0.005	0.12	-10000	0	-0.78	7	7
CHUK	0.013	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.074	0.19	-10000	0	-0.54	42	42
DAP3	0.013	0	-10000	0	-10000	0	0
CASP10	-0.051	0.16	0.28	9	-0.44	39	48
JNK cascade	-0.037	0.14	-10000	0	-0.59	19	19
TRAIL (trimer)	-0.005	0.12	-10000	0	-0.78	7	7
TNFRSF10C	-0.005	0.12	-10000	0	-0.78	7	7
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.064	0.16	-10000	0	-0.46	42	42
TRAIL/TRAILR2/FADD	-0.074	0.19	-10000	0	-0.54	42	42
cell death	-0.006	0.037	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.11	-10000	0	-0.54	1	1
TRAILR2 (trimer)	0.013	0	-10000	0	-10000	0	0
CASP8	0	0.023	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.063	0.16	-10000	0	-0.78	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.009	0.044	-9999	-0.65	1	1
VDR	0.013	0	-9999	-10000	0	0
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.011	0.12	-9999	-0.45	2	2
RXRs/LXRs/DNA/Oxysterols	0.021	0.12	-9999	-0.52	2	2
MED1	0.011	0.047	-9999	-0.8	1	1
mol:9cRA	0.005	0.012	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.012	0.12	-9999	-0.55	4	4
RXRs/NUR77	-0.017	0.15	-9999	-0.44	9	9
RXRs/PPAR	-0.11	0.18	-9999	-0.51	21	21
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.037	0.1	-9999	-10000	0	0
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.038	0.11	-9999	-0.36	5	5
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.016	0.041	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.012	0.12	-9999	-0.55	4	4
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.014	0.14	-9999	-0.36	42	42
NR1H4	0.004	0.006	-9999	-10000	0	0
RXRs/LXRs/DNA	0.007	0.14	-9999	-0.45	2	2
NR1H2	0.019	0.008	-9999	-10000	0	0
NR1H3	0.014	0.066	-9999	-0.79	2	2
RXRs/VDR/DNA/Vit D3	-0.009	0.13	-9999	-0.42	7	7
NR4A1	0	0.091	-9999	-0.64	6	6
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.001	0.095	-9999	-0.37	3	3
RXRG	-0.076	0.23	-9999	-0.66	42	42
RXR alpha/CCPG	0.003	0.008	-9999	-10000	0	0
RXRA	0.019	0.008	-9999	-10000	0	0
RXRB	0.019	0.009	-9999	-10000	0	0
THRB	-0.028	0.16	-9999	-0.64	19	19
PPARG	-0.24	0.32	-9999	-0.64	116	116
PPARD	0.013	0	-9999	-10000	0	0
TNF	0.007	0.2	-9999	-0.75	15	15
mol:Oxysterols	0.005	0.01	-9999	-10000	0	0
cholesterol transport	0.021	0.12	-9999	-0.51	2	2
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.06	0.21	-9999	-0.64	34	34
RXRs/NUR77/BCL2	-0.017	0.11	-9999	-0.3	4	4
SREBF1	0.03	0.11	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.014	0.14	-9999	-0.36	42	42
ABCA1	0.026	0.13	-9999	-0.84	2	2
RARs/THRs	-0.057	0.14	-9999	-0.67	4	4
RXRs/FXR	-0.015	0.14	-9999	-0.45	7	7
BCL2	0.004	0.08	-9999	-0.68	4	4

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.05	-9999	-0.62	2	2
PDGFRB	-0.22	0.36	-9999	-0.8	85	85
SPHK1	-0.022	0.037	-9999	-0.37	1	1
mol:S1P	-0.029	0.058	-9999	-0.44	4	4
S1P1/S1P/Gi	-0.015	0.13	-9999	-0.49	5	5
GNAO1	0.007	0.061	-9999	-0.73	2	2
PDGFB-D/PDGFRB/PLCgamma1	-0.098	0.21	-9999	-0.58	11	11
PLCG1	-0.017	0.13	-9999	-0.46	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.22	0.36	-9999	-0.8	85	85
GNAI2	0.011	0.005	-9999	-10000	0	0
GNAI3	0.009	0.007	-9999	-10000	0	0
GNAI1	0.007	0.039	-9999	-0.65	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.014	0.046	-9999	-0.54	2	2
S1P1/S1P	-0.038	0.068	-9999	-0.48	3	3
negative regulation of cAMP metabolic process	-0.015	0.12	-9999	-0.48	5	5
MAPK3	-0.022	0.16	-9999	-0.56	7	7
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	0.009	0.047	-9999	-0.8	1	1
PLCB2	-0.001	0.081	-9999	-0.42	3	3
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.031	0.057	-9999	-0.4	3	3
receptor internalization	-0.036	0.064	-9999	-0.44	3	3
PTGS2	-0.05	0.24	-9999	-0.72	14	14
Rac1/GTP	-0.031	0.057	-9999	-0.4	3	3
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.009	0.048	-9999	-0.82	1	1
negative regulation of T cell proliferation	-0.015	0.12	-9999	-0.48	5	5
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.008	0.11	-9999	-0.74	7	7
MAPK1	-0.022	0.16	-9999	-0.56	7	7
S1P1/S1P/PDGFB-D/PDGFRB	-0.09	0.2	-9999	-0.55	10	10
ABCC1	0.004	0.081	-9999	-0.8	3	3

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.013	0	-9999	-10000	0	0
VDR	0.013	0	-9999	-10000	0	0
Cbp/p300/PCAF	-0.017	0.08	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.005	0.1	-9999	-0.49	6	6
KAT2B	-0.015	0.13	-9999	-0.64	13	13
MAPK14	0.013	0	-9999	-10000	0	0
AKT1	0.018	0.12	-9999	-0.28	25	25
RAR alpha/9cRA/Cyclin H	-0.018	0.053	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.001	0.11	-9999	-0.45	7	7
CDC2	0.001	0.001	-9999	-10000	0	0
response to UV	0.001	0.002	-9999	-10000	0	0
RAR alpha/Jnk1	-0.021	0.068	-9999	-0.52	2	2
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.004	0.14	-9999	-0.52	3	3
NCOA2	0.005	0.075	-9999	-0.64	4	4
NCOA3	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0	-9999	-10000	0	0
RARG	0.014	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0.014	0.001	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
MAPK8	0.01	0.053	-9999	-0.64	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.099	-9999	-0.41	8	8
RARA	0.004	0.079	-9999	-0.26	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.006	0.13	-9999	-0.53	9	9
PRKCA	0.014	0.047	-9999	-0.8	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.019	0.14	-9999	-0.44	11	11
RXRG	-0.063	0.19	-9999	-0.41	64	64
RXRA	0.014	0.075	-9999	-10000	0	0
RXRB	-0.008	0.11	-9999	-0.34	30	30
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RBP1	-0.15	0.33	-9999	-0.8	61	61
CRBP1/9-cic-RA	-0.12	0.25	-9999	-0.62	61	61
RARB	-0.058	0.21	-9999	-0.64	34	34
PRKCG	-0.065	0.24	-9999	-0.8	29	29
MNAT1	0.013	0	-9999	-10000	0	0
RAR alpha/RXRs	0.01	0.14	-9999	-0.51	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.002	0.13	-9999	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.11	-9999	-0.44	9	9
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.019	0.14	-9999	-0.44	11	11
positive regulation of DNA binding	-0.018	0.051	-9999	-10000	0	0
NRIP1	-0.017	0.14	-9999	-1.2	1	1
RXRs/RARs	-0.025	0.14	-9999	-0.43	12	12
RXRs/RXRs/DNA/9cRA	-0.045	0.1	-9999	-0.43	8	8
PRKACA	0.013	0	-9999	-10000	0	0
CDK7	0.013	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.013	0.037	-9999	-10000	0	0
CCNH	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	-0.035	0.12	-10000	0	-0.47	18	18
ER alpha/Gai/GDP/Gbeta gamma	0.024	0.094	-10000	0	-0.46	3	3
AKT1	0.015	0.13	-10000	0	-0.78	6	6
PIK3CA	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.011	0.13	-10000	0	-0.79	6	6
mol:Ca2+	-0.034	0.17	-10000	0	-0.65	5	5
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.029	0.12	-10000	0	-0.48	18	18
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.016	0.12	0.74	6	-10000	0	6
RhoA/GTP	-0.02	0.083	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.024	0.086	-10000	0	-0.59	1	1
regulation of stress fiber formation	-0.038	0.078	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.039	0.14	-10000	0	-0.52	23	23
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.025	0.1	-10000	0	-0.45	17	17
pseudopodium formation	0.038	0.078	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.027	0.11	-10000	0	-0.49	17	17
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.011	0.047	-10000	0	-0.8	1	1
GNAO1	0.009	0.06	-10000	0	-0.72	2	2
HRAS	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.025	0.11	-10000	0	-0.51	7	7
E2/ER beta (dimer)	-0.014	0.091	-10000	0	-0.6	7	7
mol:GDP	-0.03	0.11	-10000	0	-0.5	6	6
mol:NADP	0.025	0.11	-10000	0	-0.51	7	7
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.037	0.18	-10000	0	-0.68	5	5
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.045	0.18	-10000	0	-0.43	50	50
PLCB2	-0.045	0.18	-10000	0	-0.43	50	50
IGF1	-0.054	0.2	-10000	0	-0.67	30	30
mol:L-citrulline	0.025	0.11	-10000	0	-0.51	7	7
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.01	0.058	-10000	0	-0.57	2	2
JNK cascade	-0.014	0.09	-10000	0	-0.6	7	7
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	-0.005	0.12	-10000	0	-0.78	7	7
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.029	0.18	-10000	0	-0.75	17	17
Gq family/GDP/Gbeta gamma	-0.002	0.1	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.029	0.064	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.024	0.086	-10000	0	-0.59	1	1
GNAZ	-0.004	0.11	-10000	0	-0.73	7	7
E2/ER alpha (dimer)	-0.032	0.13	-10000	0	-0.57	17	17
STRN	0.011	0.038	-10000	0	-0.64	1	1
GNAL	-0.06	0.21	-10000	0	-0.64	34	34
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.008	0.081	-10000	0	-0.52	7	7
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.011	0.038	-10000	0	-0.64	1	1
HBEGF	-0.18	0.17	-10000	0	-0.45	62	62
cAMP biosynthetic process	-0.068	0.15	-10000	0	-0.47	19	19
SRC	0.031	0.09	-10000	0	-0.55	1	1
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.028	0.097	-10000	0	-0.73	1	1
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.042	0.1	-10000	0	-0.6	2	2
Gs family/GTP	-0.069	0.15	-10000	0	-0.48	19	19
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.026	0.1	-10000	0	-0.49	7	7
mol:DAG	-0.037	0.18	-10000	0	-0.68	5	5
Gs family/GDP/Gbeta gamma	-0.053	0.12	-10000	0	-0.62	3	3
MSN	0.039	0.083	-10000	0	-10000	0	0
Gq family/GTP	-0.084	0.17	-10000	0	-0.46	50	50
mol:PI-3-4-5-P3	0.012	0.12	-10000	0	-0.76	6	6
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.026	0.1	0.49	7	-10000	0	7
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.028	0.1	-10000	0	-0.46	6	6
NOS3	0.025	0.11	-10000	0	-0.54	7	7
GNA11	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	0.037	0.11	-10000	0	-0.58	6	6
E2/ER alpha (dimer)/PELP1/Src	-0.026	0.091	-10000	0	-0.48	6	6
ruffle organization	0.038	0.078	-10000	0	-10000	0	0
ROCK2	0.031	0.09	-10000	0	-10000	0	0
GNA14	-0.095	0.24	-10000	0	-0.64	50	50
GNA15	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.3	0.2	-10000	0	-0.64	20	20
MMP2	-0.052	0.19	-10000	0	-0.55	3	3

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.22	0.37	-9999	-0.8	85	85
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	0.027	0.059	-9999	-0.56	1	1
GNAO1	0.01	0.061	-9999	-0.73	2	2
S1P/S1P3/G12/G13	-0.007	0.057	-9999	-0.44	5	5
AKT1	-0.07	0.11	-9999	-0.36	5	5
AKT3	0.039	0.11	-9999	-0.67	6	6
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.22	0.37	-9999	-0.8	85	85
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.013	0.038	-9999	-0.64	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.008	0.072	-9999	-0.71	3	3
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.034	0.081	-9999	-0.62	3	3
MAPK3	0.041	0.078	-9999	-0.59	3	3
MAPK1	0.041	0.078	-9999	-0.59	3	3
JAK2	0.036	0.1	-9999	-0.64	4	4
CXCR4	0.022	0.14	-9999	-0.55	13	13
FLT1	0.016	0.002	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.041	0.078	-9999	-0.59	3	3
S1P/S1P3/Gi	0.034	0.082	-9999	-0.63	3	3
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.012	0.066	-9999	-0.57	3	3
VEGFA	0.014	0.047	-9999	-0.8	1	1
S1P/S1P2/Gi	0.035	0.056	-9999	-0.58	1	1
VEGFR1 homodimer/VEGFA homodimer	0.026	0.037	-9999	-0.61	1	1
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.019	0.12	-9999	-0.56	1	1
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	-0.002	0.11	-9999	-0.73	7	7
G12/G13	-0.004	0.05	-9999	-0.61	2	2
GNA14	-0.095	0.24	-9999	-0.64	50	50
GNA15	0.013	0	-9999	-10000	0	0
GNA12	0.008	0.066	-9999	-0.8	2	2
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.012	0.066	-9999	-0.57	3	3

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.04	0.11	-10000	0	-0.34	35	35
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.002	0.031	-10000	0	-0.54	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.042	0.12	-10000	0	-0.38	34	34
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	0.03	0.094	34	-10000	0	34
GNAL	-0.06	0.21	-10000	0	-0.64	34	34
GNG2	0.011	0.047	-10000	0	-0.8	1	1
CRH	0.001	0.003	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.032	-10000	0	-0.38	2	2
MAPK11	0.009	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.011	0.047	-10000	0	-0.8	1	1
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	-0.14	0.32	-10000	0	-0.8	58	58
CDKN1A	0.03	0.032	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.008	0.07	-10000	0	-0.61	4	4
mol:Ca2+	-0.074	0.18	0.37	3	-0.49	48	51
AGT	-0.091	0.24	-10000	0	-0.65	48	48
CCNA2	0.032	0.079	-10000	0	-0.78	1	1
TUBA1B	0.013	0	-10000	0	-10000	0	0
EGR1	0.009	0.092	-10000	0	-0.46	11	11
CDK2/Cyclin E1	-0.005	0.031	-10000	0	-0.43	1	1
MAPK3	0.016	0.073	-10000	0	-0.61	4	4
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.073	-10000	0	-0.61	4	4
PTP4A1	0.027	0.072	-10000	0	-10000	0	0
PTP4A3	0.003	0.093	-10000	0	-0.8	4	4
PTP4A2	0.013	0	-10000	0	-10000	0	0
ITGB1	0.014	0.081	-10000	0	-0.61	5	5
SRC	0.013	0	-10000	0	-10000	0	0
RAC1	0.027	0.043	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.022	0.094	-10000	0	-10000	0	0
RABGGTA	0.013	0	-10000	0	-10000	0	0
BCAR1	0.005	0.042	0.37	4	-10000	0	4
RHOC	0.027	0.043	-10000	0	-10000	0	0
RHOA	0.027	0.043	-10000	0	-10000	0	0
cell motility	0.032	0.045	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.032	0.067	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.12	0.25	-10000	0	-0.61	62	62
ROCK1	0.032	0.046	-10000	0	-10000	0	0
RABGGTB	0.013	0	-10000	0	-10000	0	0
CDK2	0.013	0	-10000	0	-10000	0	0
mitosis	0.027	0.071	-10000	0	-10000	0	0
ATF5	-0.003	0.11	-10000	0	-0.8	6	6

×

Class IB PI3K non-lipid kinase 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.004	0.12	0.75	7	-10000	0	7
PI3K Class IB/PDE3B	-0.004	0.12	-10000	0	-0.76	7	7
PDE3B	-0.004	0.12	-10000	0	-0.76	7	7

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	-0.042	0.21	-9999	-1	12	12
MAP4K1	-0.012	0.14	-9999	-0.75	10	10
MAP3K8	0.013	0	-9999	-10000	0	0
PRKCB	-0.005	0.12	-9999	-0.78	7	7
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.011	0.047	-9999	-0.8	1	1
MAP3K1	0.026	0.12	-9999	-0.56	10	10
JUN	0.026	0.086	-9999	-0.57	4	4
MAP3K7	0.026	0.12	-9999	-0.56	10	10
GRAP2	-0.007	0.12	-9999	-0.74	8	8
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.036	0.11	-9999	-0.53	10	10
LAT	-0.008	0.13	-9999	-0.8	8	8
LCP2	0.005	0.081	-9999	-0.8	3	3
MAPK8	0.019	0.091	-9999	-0.51	7	7
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.018	0.12	-9999	-0.6	10	10
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.04	0.2	-9999	-1	10	10

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0.047	-9999	-0.8	1	1
ITGB7	0.011	0.038	-9999	-0.64	1	1
ITGA4	-0.014	0.15	-9999	-0.8	10	10
alpha4/beta7 Integrin	-0.022	0.11	-9999	-0.6	11	11
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.61	11	11

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.076	0.16	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.011	0.047	-9999	-0.8	1	1
STAT1 (dimer)/Cbp/p300	-0.091	0.19	-9999	-0.71	15	15
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.012	0.024	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.07	0.094	-9999	-0.36	5	5
CaM/Ca2+	-0.07	0.14	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.061	0.23	-9999	-0.81	15	15
AKT1	-0.015	0.15	-9999	-10000	0	0
MAP2K1	-0.016	0.16	-9999	-10000	0	0
MAP3K11	-0.029	0.17	-9999	-10000	0	0
IFNGR1	0.008	0.015	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.24	-9999	-0.66	41	41
Rap1/GTP	-0.054	0.11	-9999	-10000	0	0
CRKL/C3G	-0.002	0.035	-9999	-0.61	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.083	0.17	-9999	-10000	0	0
CEBPB	0.02	0.15	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.11	0.22	-9999	-0.9	10	10
STAT1	-0.06	0.23	-9999	-0.81	15	15
CALM1	0.014	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.14	0.32	-9999	-0.79	59	59
PIK3CA	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.087	0.2	-9999	-0.75	15	15
CEBPB/PTGES2/Cbp/p300	-0.034	0.066	-9999	-10000	0	0
mol:Ca2+	-0.075	0.15	-9999	-10000	0	0
MAPK3	0.002	0.14	-9999	-10000	0	0
STAT1 (dimer)	-0.094	0.13	-9999	-0.54	5	5
MAPK1	0.002	0.14	-9999	-10000	0	0
JAK2	0.008	0.015	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.008	0.015	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.03	0.12	-9999	-0.63	4	4
SMAD7	0.001	0.076	-9999	-10000	0	0
CBL/CRKL/C3G	-0.065	0.13	-9999	-10000	0	0
PI3K	-0.068	0.14	-9999	-10000	0	0
IFNG	-0.14	0.32	-9999	-0.79	59	59
apoptosis	0.013	0.1	-9999	-0.44	4	4
CAMK2G	0.014	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.12	0.27	-9999	-0.65	62	62
CAMK2B	-0.16	0.29	-9999	-0.65	79	79
FRAP1	-0.008	0.14	-9999	-10000	0	0
PRKCD	-0.01	0.15	-9999	-10000	0	0
RAP1B	0.011	0.047	-9999	-0.8	1	1
negative regulation of cell growth	-0.07	0.094	-9999	-0.36	5	5
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0.001	-9999	-10000	0	0
IRF1	-0.02	0.19	-9999	-0.53	15	15
STAT1 (dimer)/PIASy	-0.086	0.2	-9999	-0.75	15	15
SOCS1	-0.046	0.18	-9999	-0.65	25	25
mol:GDP	-0.062	0.12	-9999	-10000	0	0
CASP1	0.001	0.078	-9999	-0.38	1	1
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.041	0.055	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.066	0.13	-9999	-10000	0	0
RAP1/GDP	-0.055	0.11	-9999	-10000	0	0
CBL	-0.03	0.16	-9999	-10000	0	0
MAP3K1	-0.028	0.17	-9999	-10000	0	0
PIAS1	0.013	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	0.094	-9999	-0.36	5	5
PTPN11	-0.04	0.17	-9999	-10000	0	0
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.006	0.036	0.26	1	-10000	0	1
RFC1	0.006	0.036	0.26	4	-10000	0	4
PRKDC	0.006	0.036	0.26	3	-10000	0	3
RIPK1	0.013	0.003	-10000	0	-10000	0	0
CASP7	-0.011	0.041	0.23	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.05	0.12	-10000	0	-0.39	9	9
MAP2K4	0	0.12	-10000	0	-0.44	7	7
mol:ceramide	-0.019	0.14	-10000	0	-0.47	9	9
GSN	0.006	0.036	0.26	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 8	-0.019	0.12	-10000	0	-0.46	6	6
FAS	0.013	0.004	-10000	0	-10000	0	0
BID	0.003	0.045	-10000	0	-0.54	1	1
MAP3K1	0.012	0.077	-10000	0	-10000	0	0
MAP3K7	0.013	0.004	-10000	0	-10000	0	0
RB1	0.005	0.042	0.26	1	-0.39	1	2
CFLAR	0.013	0.003	-10000	0	-10000	0	0
HGF/MET	-0.02	0.092	-10000	0	-0.53	4	4
ARHGDIB	0.006	0.036	0.26	4	-10000	0	4
FADD	-0.084	0.26	-10000	0	-0.8	36	36
actin filament polymerization	-0.006	0.036	-10000	0	-0.26	4	4
NFKB1	-0.029	0.063	-10000	0	-10000	0	0
MAPK8	-0.005	0.16	-10000	0	-0.57	8	8
DFFA	0.006	0.036	0.26	4	-10000	0	4
DNA fragmentation during apoptosis	0.006	0.036	-10000	0	-10000	0	0
FAS/FADD/MET	-0.066	0.18	-10000	0	-0.54	37	37
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.003	0.11	-10000	0	-0.8	6	6
FAF1	0.014	0.004	-10000	0	-10000	0	0
PARP1	0.006	0.036	0.26	4	-10000	0	4
DFFB	0.006	0.036	-10000	0	-10000	0	0
CHUK	-0.024	0.054	-10000	0	-10000	0	0
FASLG	-0.039	0.2	-10000	0	-0.75	21	21
FAS/FADD	-0.073	0.2	-10000	0	-0.61	36	36
HGF	-0.008	0.12	-10000	0	-0.7	9	9
LMNA	0.006	0.033	-10000	0	-10000	0	0
CASP6	0.006	0.036	0.26	3	-10000	0	3
CASP10	0.013	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.042	0.3	4	-10000	0	4
PTPN13	0.007	0.065	-10000	0	-0.64	3	3
CASP8	0.007	0.052	0.37	6	-10000	0	6
IL6	-0.082	0.36	-10000	0	-1.2	28	28
MET	0.009	0.06	-10000	0	-0.72	2	2
ICAD/CAD	0.006	0.034	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.02	0.14	-10000	0	-0.49	8	8
activation of caspase activity by cytochrome c	0.003	0.045	-10000	0	-0.54	1	1
PAK2	0.006	0.035	0.25	3	-10000	0	3
BCL2	0.004	0.08	-10000	0	-0.68	4	4

×

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	0.036	0.12	-10000	0	-0.69	4	4
UGCG	-0.007	0.037	-10000	0	-0.59	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.011	0.13	-10000	0	-0.43	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.019	0.044	-10000	0	-0.58	1	1
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.025	0.083	-10000	0	-0.45	8	8
FRAP1	0.047	0.13	-10000	0	-0.52	8	8
FOXO3	0.055	0.12	-10000	0	-0.55	4	4
AKT1	0.048	0.12	-10000	0	-0.57	5	5
GAB2	0.01	0.053	-10000	0	-0.64	2	2
SMPD1	-0.005	0.015	-10000	0	-10000	0	0
SGMS1	-0.005	0.015	-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	0.024	0.003	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	0.038	0.056	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.024	0.009	-10000	0	-10000	0	0
RPS6KB1	0.006	0.069	-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	-0.026	0.18	-10000	0	-0.8	16	16
PIK3R1	0.017	0.002	-10000	0	-10000	0	0
JAK1	0.017	0.002	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
MYC	0.056	0.11	-10000	0	-0.53	2	2
MYB	-0.11	0.39	-10000	0	-1.2	31	31
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.033	0.13	-10000	0	-0.55	10	10
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.063	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.13	-10000	0	-0.54	10	10
Rac1/GDP	0.028	0.01	-10000	0	-10000	0	0
T cell proliferation	0.043	0.12	-10000	0	-0.52	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	0.022	-10000	0	-0.066	31	31
PRKCZ	0.042	0.13	-10000	0	-0.54	8	8
NF kappa B1 p50/RelA	-0.023	0.082	-10000	0	-0.46	5	5
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.029	0.13	-10000	0	-0.54	12	12
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.085	0.27	-10000	0	-0.8	37	37
IL2RB	0	0.11	-10000	0	-0.8	6	6
TERT	-0.16	0.34	-10000	0	-0.8	66	66
E2F1	-0.029	0.15	-10000	0	-0.43	31	31
SOS1	0.014	0.002	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	0	0.011	0.032	31	-10000	0	31
PTPN11	0.014	0.002	-10000	0	-10000	0	0
IL2RG	-0.012	0.15	-10000	0	-0.78	11	11
actin cytoskeleton organization	0.043	0.12	-10000	0	-0.52	8	8
GRB2	0.014	0.002	-10000	0	-10000	0	0
IL2	0.005	0.047	-10000	0	-0.8	1	1
PIK3CA	0.017	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.035	0.012	-10000	0	-10000	0	0
LCK	-0.01	0.15	-10000	0	-0.8	10	10
BCL2	0.049	0.14	-10000	0	-0.78	5	5

×

Stabilization and expansion of the E-cadherin adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.031	0.03	-9999	-10000	0	0
epithelial cell differentiation	-0.003	0.033	-9999	-10000	0	0
CYFIP2	0.009	0.053	-9999	-0.64	2	2
ENAH	0.066	0.042	-9999	-10000	0	0
EGFR	-0.014	0.15	-9999	-0.8	10	10
EPHA2	0.005	0.075	-9999	-0.64	4	4
MYO6	0.037	0.04	-9999	-10000	0	0
CTNNB1	0.011	0.038	-9999	-0.64	1	1
ABI1/Sra1/Nap1	-0.003	0.032	-9999	-0.4	2	2
AQP5	-0.37	0.21	-9999	-0.49	228	228
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.038	0.034	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.005	0.12	-9999	-10000	0	0
EGF	-0.14	0.27	-9999	-0.64	69	69
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.14	0.22	-9999	-0.49	87	87
cortical microtubule organization	-0.003	0.033	-9999	-10000	0	0
GO:0000145	0.037	0.033	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.033	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GDP	-0.007	0.042	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.049	-9999	-0.48	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.05	0.036	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.038	0.035	-9999	-10000	0	0
ARF6/GTP	-0.006	0.044	-9999	-10000	0	0
CDH1	0.009	0.053	-9999	-0.64	2	2
EGFR/EGFR/EGF/EGF	-0.084	0.14	-9999	-0.67	2	2
RhoA/GDP	-0.003	0.03	-9999	-10000	0	0
actin cytoskeleton organization	0.044	0.038	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.054	0.2	-9999	-0.67	30	30
DIAPH1	-0.004	0.048	-9999	-0.6	2	2
Wnt receptor signaling pathway	0.003	0.033	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.007	0.042	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.044	0.039	-9999	-10000	0	0
EFNA1	0.011	0.047	-9999	-0.8	1	1
LPP	0.044	0.042	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.008	0.05	-9999	-10000	0	0
SEC6/SEC8	-0.003	0.026	-9999	-10000	0	0
MGAT3	0.005	0.12	-9999	-10000	0	0
HGF/MET	-0.015	0.076	-9999	-0.73	1	1
HGF	-0.008	0.12	-9999	-0.7	9	9
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.031	0.03	-9999	-10000	0	0
actin cable formation	0.084	0.038	-9999	-10000	0	0
KIAA1543	0.019	0.11	-9999	-0.72	3	3
KIFC3	0.038	0.035	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.037	0.044	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.003	0.033	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.038	0.035	-9999	-10000	0	0
PIP5K1C	0.038	0.035	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	-0.006	0.036	-9999	-10000	0	0
adherens junction assembly	0.037	0.11	-9999	-0.67	3	3
IGF-1R heterotetramer/IGF1	-0.034	0.098	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.009	0.06	-9999	-0.72	2	2
PLEKHA7	0.021	0.088	-9999	-0.64	1	1
mol:GTP	-0.006	0.048	-9999	-0.48	1	1
establishment of epithelial cell apical/basal polarity	0.065	0.031	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.031	0.03	-9999	-10000	0	0
regulation of cell-cell adhesion	0.044	0.038	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.031	0.03	-9999	-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	-0.018	0.18	-9999	-0.56	10	10
MAP3K8	0.012	0.005	-9999	-10000	0	0
FOS	0	0.12	-9999	-0.46	9	9
PRKCA	0.01	0.047	-9999	-0.8	1	1
PTPN7	-0.029	0.18	-9999	-0.8	16	16
HRAS	0.013	0.001	-9999	-10000	0	0
PRKCB	-0.006	0.12	-9999	-0.79	7	7
NRAS	0.013	0.001	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.006	0.086	-9999	-0.38	7	7
MAP2K1	0.025	0.072	-9999	-0.43	3	3
ELK1	0.008	0.049	-9999	-0.84	1	1
BRAF	-0.013	0.059	-9999	-0.42	3	3
mol:GTP	-0.001	0.002	-9999	-0.006	48	48
MAPK1	0.006	0.086	-9999	-0.38	7	7
RAF1	-0.013	0.059	-9999	-0.42	3	3
KRAS	0.013	0.001	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.031	0.12	-10000	0	-0.57	1	1
CRKL	0.006	0.13	-10000	0	-0.48	1	1
mol:DAG	0.018	0.12	-10000	0	-0.47	1	1
HRAS	0.037	0.12	-10000	0	-10000	0	0
MAPK8	-0.012	0.15	-10000	0	-0.44	32	32
RAP1A	0.008	0.13	-10000	0	-0.48	1	1
GAB1	0.008	0.13	-10000	0	-0.48	1	1
MAPK14	-0.01	0.15	-10000	0	-0.44	32	32
EPO	-0.053	0.22	-10000	0	-0.8	25	25
PLCG1	0.017	0.12	-10000	0	-0.49	1	1
EPOR/TRPC2/IP3 Receptors	-0.005	0.12	-10000	0	-0.79	7	7
RAPGEF1	0.013	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.054	0.16	-10000	0	-0.5	33	33
GAB1/SHC/GRB2/SOS1	-0.034	0.097	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.043	0.19	-10000	0	-0.6	32	32
IRS2	0.005	0.13	-10000	0	-0.48	1	1
STAT1	-0.003	0.16	-10000	0	-0.63	2	2
STAT5B	0.022	0.12	-10000	0	-0.54	1	1
cell proliferation	-0.002	0.14	-10000	0	-0.45	1	1
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.033	0.096	-10000	0	-0.66	1	1
TEC	-0.012	0.16	-10000	0	-0.72	4	4
SOCS3	0.011	0.038	-10000	0	-0.64	1	1
STAT1 (dimer)	-0.002	0.16	-10000	0	-0.62	2	2
JAK2	0.012	0.012	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.01	0.14	-10000	0	-0.51	1	1
EPO/EPOR	-0.043	0.19	-10000	0	-0.6	32	32
LYN	0.015	0.002	-10000	0	-10000	0	0
TEC/VAV2	-0.019	0.18	-10000	0	-0.79	5	5
elevation of cytosolic calcium ion concentration	-0.005	0.12	-10000	0	-0.79	7	7
SHC1	0.013	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.017	0.17	-10000	0	-0.5	32	32
mol:IP3	0.018	0.12	-10000	0	-0.47	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.039	0.11	-10000	0	-0.74	1	1
SH2B3	0.009	0.048	-10000	0	-0.79	1	1
NFKB1	-0.01	0.15	-10000	0	-0.44	32	32
EPO/EPOR (dimer)/JAK2/SOCS3	-0.027	0.083	0.27	1	-0.29	1	2
PTPN6	-0.001	0.14	-10000	0	-0.51	1	1
TEC/VAV2/GRB2	-0.054	0.16	-10000	0	-0.76	5	5
EPOR	-0.005	0.12	-10000	0	-0.79	7	7
INPP5D	0.011	0.038	-10000	0	-0.64	1	1
mol:GDP	-0.035	0.099	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
PLCG2	0.013	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.025	0.11	-10000	0	-10000	0	0
VAV2	-0.009	0.16	-10000	0	-0.7	3	3
CBL	0.008	0.13	-10000	0	-0.48	1	1
SHC/Grb2/SOS1	-0.037	0.1	-10000	0	-10000	0	0
STAT5A	0.022	0.12	-10000	0	-0.54	1	1
GRB2	0.013	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.04	0.13	-10000	0	-0.65	1	1
LYN/PLCgamma2	0	0	-10000	0	-10000	0	0
PTPN11	0.013	0	-10000	0	-10000	0	0
BTK	0.006	0.13	-10000	0	-0.48	1	1
BCL2	0.025	0.15	-10000	0	-0.95	3	3

×

Ceramide signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.089	-10000	0	-0.61	6	6
MAP4K4	0.03	0.077	-10000	0	-0.46	2	2
BAG4	0.013	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.018	0.053	0.21	1	-0.41	1	2
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.17	-10000	0	-0.8	14	14
BAX	-0.004	0.025	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.024	0.011	-10000	0	-10000	0	0
BAD	-0.016	0.049	0.21	5	-10000	0	5
SMPD1	0.019	0.053	-10000	0	-0.26	2	2
RB1	-0.017	0.053	0.23	1	-0.36	1	2
FADD/Caspase 8	-0.012	0.17	-10000	0	-0.6	6	6
MAP2K4	-0.007	0.046	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.007	0.046	-10000	0	-10000	0	0
EGF	-0.14	0.27	-10000	0	-0.64	69	69
mol:ceramide	-0.027	0.053	0.22	5	-10000	0	5
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.012	0.089	-10000	0	-0.61	6	6
ASAH1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.017	0.053	0.23	1	-0.36	1	2
cell proliferation	-0.038	0.087	-10000	0	-0.36	5	5
BID	0.019	0.055	-10000	0	-10000	0	0
MAP3K1	-0.016	0.049	0.21	5	-10000	0	5
EIF2A	-0.001	0.057	-10000	0	-0.43	2	2
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.006	0.044	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.044	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.016	0.048	0.19	5	-10000	0	5
FADD	-0.027	0.18	-10000	0	-0.46	38	38
KSR1	-0.016	0.049	0.21	5	-10000	0	5
MAPK8	-0.004	0.052	0.22	1	-0.29	1	2
PRKRA	-0.016	0.049	0.21	5	-10000	0	5
PDGFA	-0.003	0.11	-10000	0	-0.8	6	6
TRAF2	0.008	0.066	-10000	0	-0.8	2	2
IGF1	-0.054	0.2	-10000	0	-0.67	30	30
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.027	0.052	0.22	5	-10000	0	5
CTSD	0.013	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	-0.019	0.1	-10000	0	-0.39	5	5
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.038	-10000	0	-0.64	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.012	0.089	-10000	0	-0.61	6	6
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.023	0.081	-10000	0	-0.46	3	3
TNFR1A/BAG4/TNF-alpha	-0.024	0.11	-10000	0	-0.49	15	15
mol:Sphingosine-1-phosphate	0.012	0.089	-10000	0	-0.61	6	6
MAP2K1	0.002	0.044	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	-0.006	0.041	0.22	3	-10000	0	3
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0	0	-10000	0	-10000	0	0
EIF2AK2	-0.01	0.059	-10000	0	-0.46	2	2
TNF-alpha/TNFR1A/FAN	-0.024	0.11	-10000	0	-0.49	15	15
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.035	0.046	-10000	0	-10000	0	0
MAP2K2	0.002	0.044	-10000	0	-10000	0	0
SMPD3	-0.006	0.11	-10000	0	-0.34	25	25
TNF	-0.025	0.17	-10000	0	-0.76	15	15
PKC zeta/PAR4	-0.002	0.027	-10000	0	-0.47	1	1
mol:PHOSPHOCHOLINE	0.043	0.11	0.24	72	-10000	0	72
NF kappa B1/RelA/I kappa B alpha	-0.001	0.019	-10000	0	-10000	0	0
AIFM1	-0.006	0.041	0.22	3	-10000	0	3
BCL2	0.004	0.08	-10000	0	-0.68	4	4

×

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

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
BAG4	0.013	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.033	0.075	-9999	-0.5	2	2
NEF	-0.006	0.045	-9999	-10000	0	0
NFKBIA	0.012	0.026	-9999	-10000	0	0
BIRC3	0.013	0.16	-9999	-0.74	14	14
CYCS	0.01	0.11	-9999	-0.53	3	3
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.031	0.19	-9999	-0.86	14	14
MAP2K7	0.012	0.094	-9999	-0.43	2	2
protein ubiquitination	0.031	0.096	-9999	-0.42	1	1
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	0.002	0.11	-9999	-0.52	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.015	0.067	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
CFLAR	0.013	0	-9999	-10000	0	0
FADD	-0.084	0.26	-9999	-0.8	36	36
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.015	0.067	-9999	-10000	0	0
MAPK8	0.018	0.096	-9999	-0.44	2	2
APAF1	0.013	0	-9999	-10000	0	0
TRAF1	-0.008	0.13	-9999	-0.8	8	8
TRAF2	0.008	0.066	-9999	-0.8	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.006	0.11	-9999	-0.49	4	4
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.014	0.12	-9999	-0.52	2	2
CHUK	0.031	0.1	-9999	-0.46	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.053	0.14	-9999	-0.45	36	36
TCRz/NEF	-0.05	0.17	-9999	-0.54	28	28
TNF	-0.025	0.17	-9999	-0.76	15	15
FASLG	-0.045	0.25	-9999	-0.81	27	27
NFKB1	0.012	0.026	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.024	0.11	-9999	-0.49	15	15
CASP6	-0.02	0.046	-9999	-10000	0	0
CASP7	0.041	0.13	-9999	-0.5	4	4
RELA	0.012	0.026	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.041	0.13	-9999	-0.5	4	4
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.023	0.11	-9999	-0.48	2	2
APAF-1/Caspase 9	-0.039	0.1	-9999	-0.51	4	4
BCL2	0.021	0.1	-9999	-0.44	3	3

×

IL6-mediated signaling events

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
BCL2L1	0.001	0.22	-9999	-0.66	3	3
CRP	-0.031	0.27	-9999	-0.76	18	18
cell cycle arrest	-0.013	0.24	-9999	-0.7	9	9
TIMP1	0.01	0.2	-9999	-0.64	1	1
IL6ST	0	0.099	-9999	-0.64	7	7
Rac1/GDP	0.013	0.14	-9999	-0.58	7	7
AP1	-0.002	0.14	-9999	-0.65	2	2
GAB2	0.009	0.053	-9999	-0.64	2	2
TNFSF11	-0.078	0.32	-9999	-0.72	24	24
HSP90B1	0.035	0.052	-9999	-10000	0	0
GAB1	0.014	0.001	-9999	-10000	0	0
MAPK14	0.011	0.14	-9999	-0.63	6	6
AKT1	0.058	0.03	-9999	-10000	0	0
FOXO1	0.067	0.026	-9999	-10000	0	0
MAP2K6	-0.003	0.15	-9999	-0.64	6	6
mol:GTP	0	0.003	-9999	-10000	0	0
MAP2K4	0.02	0.16	-9999	-0.56	6	6
MITF	0.004	0.15	-9999	-0.68	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.013	0	-9999	-10000	0	0
A2M	0.02	0.039	-9999	-0.65	1	1
CEBPB	0.02	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.025	0.07	-9999	-0.39	2	2
STAT3	-0.015	0.25	-9999	-0.73	9	9
STAT1	-0.027	0.098	-9999	-0.42	9	9
CEBPD	0.001	0.22	-9999	-0.66	3	3
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	0	0.002	-9999	-10000	0	0
JUN	0.013	0.001	-9999	-10000	0	0
PIAS3/MITF	0.01	0.14	-9999	-0.64	6	6
MAPK11	0.011	0.14	-9999	-0.63	6	6
STAT3 (dimer)/FOXO1	0.045	0.21	-9999	-0.57	1	1
GRB2/SOS1/GAB family	-0.031	0.093	-9999	-0.58	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.001	0.13	-9999	-0.64	5	5
GRB2	0.014	0.001	-9999	-10000	0	0
JAK2	0.013	0	-9999	-10000	0	0
LBP	-0.1	0.38	-9999	-0.9	47	47
PIK3R1	0.015	0	-9999	-10000	0	0
JAK1	0.015	0.005	-9999	-10000	0	0
MYC	0.001	0.22	-9999	-0.66	3	3
FGG	-0.024	0.26	-9999	-0.75	16	16
macrophage differentiation	-0.013	0.24	-9999	-0.7	9	9
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.04	0.13	-9999	-0.57	8	8
JUNB	0	0.21	-9999	-0.64	3	3
FOS	-0.093	0.24	-9999	-0.64	49	49
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.002	0.14	-9999	-0.54	9	9
STAT1/PIAS1	-0.002	0.14	-9999	-0.54	7	7
GRB2/SOS1/GAB family/SHP2/PI3K	0.041	0.035	-9999	-10000	0	0
STAT3 (dimer)	-0.015	0.25	-9999	-0.72	9	9
PRKCD	0.026	0.18	-9999	-0.66	2	2
IL6R	0.013	0.038	-9999	-0.65	1	1
SOCS3	0.016	0.14	-9999	-0.78	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.02	0.069	-9999	-0.4	5	5
Rac1/GTP	-0.051	0.11	-9999	-0.58	7	7
HCK	0.003	0.084	-9999	-0.72	4	4
MAPKKK cascade	0.039	0.07	-9999	-0.56	2	2
bone resorption	-0.072	0.31	-9999	-0.68	24	24
IRF1	0.001	0.22	-9999	-0.66	3	3
mol:GDP	0.006	0.15	-9999	-0.62	7	7
SOS1	0.012	0.005	-9999	-10000	0	0
VAV1	0.006	0.15	-9999	-0.63	7	7
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.011	0.13	-9999	-0.69	5	5
PTPN11	-0.001	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.029	0.16	-9999	-0.51	28	28
gp130 (dimer)/TYK2/TYK2/LMO4	0.015	0.067	-9999	-0.4	4	4
gp130 (dimer)/JAK2/JAK2/LMO4	0.015	0.067	-9999	-0.41	1	1
IL6	-0.048	0.2	-9999	-0.67	28	28
PIAS3	0.013	0	-9999	-10000	0	0
PTPRE	0.011	0.013	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
RAC1	0.014	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.007	0.13	-9999	-0.65	5	5
LMO4	0.015	0.011	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.17	-9999	-0.71	7	7
MCL1	0.066	0.025	-9999	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.14	0.31	-9999	-1.3	1	1
PLK1	0.08	0.082	-9999	-0.69	1	1
BIRC5	0.073	0.11	-9999	-0.68	4	4
HSPA1B	0.14	0.31	-9999	-1.3	1	1
MAP2K1	0.043	0.037	-9999	-10000	0	0
BRCA2	0.14	0.32	-9999	-1.3	2	2
FOXM1	0.13	0.35	-9999	-2.1	1	1
XRCC1	0.14	0.31	-9999	-1.3	1	1
FOXM1B/p19	-0.18	0.26	-9999	-1.1	6	6
Cyclin D1/CDK4	0.082	0.36	-9999	-1	4	4
CDC2	0.14	0.32	-9999	-1.4	1	1
TGFA	0.095	0.36	-9999	-1.1	3	3
SKP2	0.14	0.31	-9999	-1.3	1	1
CCNE1	0.016	0.047	-9999	-0.78	1	1
CKS1B	0.14	0.31	-9999	-1.5	1	1
RB1	-0.049	0.1	-9999	-0.67	2	2
FOXM1C/SP1	0.13	0.31	-9999	-1.7	1	1
AURKB	0.08	0.082	-9999	-0.72	1	1
CENPF	0.14	0.31	-9999	-1.3	1	1
CDK4	0.023	0.017	-9999	-10000	0	0
MYC	0.14	0.28	-9999	-1.1	1	1
CHEK2	0.041	0.057	-9999	-0.71	1	1
ONECUT1	0.081	0.38	-9999	-1.1	6	6
CDKN2A	-0.32	0.38	-9999	-0.78	124	124
LAMA4	0.12	0.35	-9999	-1.1	4	4
FOXM1B/HNF6	0.076	0.4	-9999	-1.2	6	6
FOS	0.006	0.54	-9999	-1.1	49	49
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.13	0.32	-9999	-1.3	1	1
response to radiation	0.025	0.035	-9999	-10000	0	0
CENPB	0.14	0.31	-9999	-1.3	1	1
CENPA	0.14	0.32	-9999	-1.1	3	3
NEK2	0.14	0.32	-9999	-1.3	2	2
HIST1H2BA	0.13	0.31	-9999	-1.3	1	1
CCNA2	0.016	0.049	-9999	-0.82	1	1
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.14	0.33	-9999	-1.7	1	1
CCNB2	0.14	0.31	-9999	-1.5	1	1
CCNB1	0.14	0.32	-9999	-1.4	1	1
ETV5	0.14	0.32	-9999	-1.3	1	1
ESR1	0.11	0.36	-9999	-1	9	9
CCND1	0.086	0.38	-9999	-1.1	5	5
GSK3A	0.039	0.033	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.045	0.064	-9999	-0.52	2	2
CDK2	0.019	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.03	0.04	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.072	0.18	-9999	-1.5	1	1
GAS1	0.14	0.33	-9999	-1.2	4	4
MMP2	0.072	0.38	-9999	-1	6	6
RB1/FOXM1C	0.1	0.35	-9999	-1.1	2	2
CREBBP	0.013	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	-0.004	0.043	-9999	-0.54	2	2
ATM	0.013	0	-9999	-10000	0	0
MAP2K3	0.018	0.044	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.021	0.063	-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	0.083	-9999	-0.64	5	5
TXN	0.009	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.011	0.047	-9999	-0.8	1	1
GADD45B	0.013	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.011	0.038	-9999	-0.64	1	1
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.002	0.027	-9999	-0.47	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.008	0.066	-9999	-0.8	2	2
RAC1/OSM/MEKK3/MKK3	-0.006	0.012	-9999	-10000	0	0
TRAF6	0.009	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.16	0.29	-9999	-0.65	79	79
CCM2	0.013	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.11	0.18	-9999	-0.41	79	79
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.096	0.16	-9999	-0.37	79	79
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.017	0.023	-9999	-0.37	1	1
TAOK2	0.019	0	-9999	-10000	0	0
TAOK3	0.019	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
MAP3K10	0.011	0.047	-9999	-0.8	1	1
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.017	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.007	0.05	-9999	-0.46	1	1

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.01	0.053	-9999	-0.64	2	2
ELF1	-0.019	0.11	-9999	-10000	0	0
CCNA2	0.011	0.047	-9999	-0.8	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
JAK3	-0.029	0.18	-9999	-0.8	16	16
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.035	0.13	-9999	-0.57	9	9
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.02	0.029	-9999	-10000	0	0
IL2RA	-0.056	0.24	-9999	-0.7	37	37
IL2RB	-0.002	0.11	-9999	-0.8	6	6
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.015	0.15	-9999	-0.79	11	11
G1/S transition of mitotic cell cycle	0.037	0.073	-9999	-0.67	1	1
PTPN11	0.014	0	-9999	-10000	0	0
CCND2	0.028	0.067	-9999	-0.78	2	2
LCK	-0.013	0.15	-9999	-0.8	10	10
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.003	0.047	-9999	-0.8	1	1
CDK6	0	0.1	-9999	-0.8	5	5
CCND3	0.045	0.12	-9999	-0.59	4	4

×

IGF1 pathway

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
NCK2	0.013	0	-9999	-10000	0	0
PTK2	0.013	0	-9999	-10000	0	0
CRKL	-0.007	0.11	-9999	-0.48	1	1
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.013	0	-9999	-10000	0	0
IRS1/Crk	-0.006	0.11	-9999	-0.37	5	5
IGF-1R heterotetramer/IGF1/PTP1B	-0.038	0.12	-9999	-0.47	5	5
AKT1	0.02	0.093	-9999	-10000	0	0
BAD	0.028	0.088	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.006	0.11	-9999	-0.37	5	5
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.032	0.098	-9999	-0.37	5	5
RAF1	0.032	0.085	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.03	0.091	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.036	0.11	-9999	-0.36	30	30
PIK3CA	0.013	0	-9999	-10000	0	0
RPS6KB1	0.02	0.093	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.027	0.076	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.026	0.078	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.029	0.089	-9999	-10000	0	0
IGF-1R heterotetramer	0.006	0.025	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.032	0.098	-9999	-0.37	5	5
Crk/p130 Cas/Paxillin	-0.028	0.085	-9999	-10000	0	0
IGF1R	0.006	0.025	-9999	-10000	0	0
IGF1	-0.054	0.21	-9999	-0.67	30	30
IRS2/Crk	0.001	0.1	-9999	-10000	0	0
PI3K	-0.03	0.09	-9999	-10000	0	0
apoptosis	-0.033	0.079	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.004	0.13	-9999	-0.39	25	25
RAF1/14-3-3 E	0.038	0.077	-9999	-10000	0	0
BAD/14-3-3	0.034	0.083	-9999	-10000	0	0
PRKCZ	0.019	0.094	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.021	0.062	-9999	-10000	0	0
PTPN1	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.004	0.13	-9999	-0.42	25	25
BCAR1	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.034	0.1	-9999	-0.51	1	1
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
IRS1/NCK2	-0.006	0.11	-9999	-0.37	5	5
GRB10	0.011	0.047	-9999	-0.8	1	1
PTPN11	-0.006	0.11	-9999	-0.37	5	5
IRS1	-0.016	0.11	-9999	-0.36	30	30
IRS2	-0.008	0.11	-9999	-0.37	5	5
IGF-1R heterotetramer/IGF1	-0.05	0.15	-9999	-0.5	30	30
GRB2	0.013	0	-9999	-10000	0	0
PDPK1	0.011	0.097	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKD1	-0.004	0.14	-9999	-0.42	29	29
SHC1	0.013	0	-9999	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.05	0.12	-9999	-0.74	1	1
TC10/GTP	-0.048	0.11	-9999	-0.72	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0	0	-9999	-10000	0	0
HRAS	0.013	0	-9999	-10000	0	0
APS homodimer	0.011	0.047	-9999	-0.8	1	1
GRB14	-0.058	0.21	-9999	-0.66	32	32
FOXO3	-0.007	0.046	-9999	-0.77	1	1
AKT1	0.021	0.1	-9999	-10000	0	0
INSR	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.011	0.047	-9999	-0.8	1	1
SORBS1	-0.092	0.24	-9999	-0.64	49	49
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.039	0	-9999	-10000	0	0
CAV1	-0.018	0.15	-9999	-0.47	29	29
CBL/APS/CAP/Crk-II/C3G	-0.054	0.13	-9999	-0.78	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.042	0	-9999	-10000	0	0
RPS6KB1	0.029	0.097	-9999	-10000	0	0
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.007	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.025	0.074	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0	0	-9999	-10000	0	0
PRKCI	-0.007	0.021	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.032	0.093	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.006	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	0.021	0.1	-9999	-10000	0	0
PRKCZ	-0.009	0.036	-9999	-0.52	1	1
SH2B2	0.011	0.047	-9999	-0.8	1	1
SHC/SHIP	0.035	0.02	-9999	-10000	0	0
F2RL2	-0.29	0.4	-9999	-0.8	114	114
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.059	0.14	-9999	-0.83	1	1
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.002	0.028	-9999	-0.5	1	1
INPP5D	0.028	0.021	-9999	-0.34	1	1
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.005	0.059	-9999	-1	1	1
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
p62DOK/RasGAP	0	0.006	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.028	0.021	-9999	-0.34	1	1
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	0.025	0.1	-9999	-10000	0	0
PTPRA	0.015	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.037	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.17	0.22	-9999	-0.46	113	113

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	0.005	0.081	-9999	-0.8	3	3
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.019	0.043	-9999	-0.28	6	6
GNAO1	0.009	0.06	-9999	-0.72	2	2
mol:Sphinganine-1-P	0.019	0.063	-9999	-0.61	3	3
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.007	0.044	-9999	-0.44	2	2
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	-0.004	0.05	-9999	-0.61	2	2
S1PR3	0.006	0.071	-9999	-0.7	3	3
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.005	0.034	-9999	-10000	0	0
S1PR5	0.011	0.038	-9999	-0.64	1	1
S1PR4	-0.035	0.19	-9999	-0.8	18	18
GNAI1	0.011	0.038	-9999	-0.64	1	1
S1P/S1P5/G12	-0.008	0.051	-9999	-0.43	3	3
S1P/S1P3/Gq	-0.011	0.12	-9999	-0.49	2	2
S1P/S1P4/Gi	0.019	0.088	-9999	-0.54	2	2
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	-0.004	0.11	-9999	-0.73	7	7
GNA14	-0.095	0.24	-9999	-0.64	50	50
GNA15	0.013	0	-9999	-10000	0	0
GNA12	0.008	0.066	-9999	-0.8	2	2
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.013	0	-9999	-10000	0	0
ABCC1	0.005	0.081	-9999	-0.8	3	3

×

Circadian rhythm 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0	0.003	-9999	-10000	0	0
CLOCK	0.017	0	-9999	-10000	0	0
TIMELESS/CRY2	0.047	0.01	-9999	-10000	0	0
DEC1/BMAL1	-0.077	0.2	-9999	-0.61	38	38
ATR	0.013	0	-9999	-10000	0	0
NR1D1	0.046	0.012	-9999	-10000	0	0
ARNTL	0.017	0	-9999	-10000	0	0
TIMELESS	0.046	0.012	-9999	-10000	0	0
NPAS2	0.009	0.075	-9999	-0.64	4	4
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	-0.015	0	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	0.015	0	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.041	0.049	-9999	-0.38	4	4
BMAL1/CLOCK	0.027	0.085	-9999	-10000	0	0
S phase of mitotic cell cycle	0	0.003	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0	0.003	-9999	-10000	0	0
mol:NADPH	0.015	0	-9999	-10000	0	0
PER1/TIMELESS	0.047	0.01	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.092	0.27	-9999	-0.8	38	38

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.017	0.14	-10000	0	-0.64	13	13
regulation of axonogenesis	-0.025	0.029	-10000	0	-10000	0	0
myoblast fusion	0.02	0.069	0.32	13	-10000	0	13
mol:GTP	-0.01	0.039	-10000	0	-0.26	1	1
regulation of calcium-dependent cell-cell adhesion	-0.021	0.064	0.41	4	-10000	0	4
ARF1/GTP	-0.007	0.027	-10000	0	-10000	0	0
mol:GM1	0.003	0.032	-10000	0	-0.19	1	1
mol:Choline	0.024	0.028	-10000	0	-10000	0	0
lamellipodium assembly	-0.019	0.07	-10000	0	-0.32	13	13
MAPK3	0.018	0.059	-10000	0	-0.3	1	1
ARF6/GTP/NME1/Tiam1	0.022	0.065	-10000	0	-0.41	4	4
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.02	0.069	-10000	0	-0.32	13	13
ARF1/GDP	0.01	0.07	-10000	0	-0.51	1	1
ARF6	0.007	0.022	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	0.008	0.065	-10000	0	-0.64	3	3
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.059	-10000	0	-0.3	1	1
actin filament bundle formation	0.017	0.061	0.51	1	-10000	0	1
KALRN	-0.03	0.099	-10000	0	-0.37	18	18
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.017	0.062	-10000	0	-0.51	1	1
NME1	0.012	0.047	-10000	0	-0.8	1	1
Rac1/GDP	-0.017	0.062	-10000	0	-0.51	1	1
substrate adhesion-dependent cell spreading	-0.01	0.039	-10000	0	-0.26	1	1
cortical actin cytoskeleton organization	-0.019	0.071	-10000	0	-0.32	13	13
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.01	0.039	-10000	0	-0.26	1	1
ARF6/GTP	-0.01	0.039	-10000	0	-0.26	1	1
RhoA/GTP	-0.007	0.027	-10000	0	-10000	0	0
mol:GDP	-0.019	0.071	-10000	0	-0.32	13	13
ARF6/GTP/RAB11FIP3/RAB11A	-0.004	0.021	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0.015	0.032	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.019	0.07	-10000	0	-0.32	13	13
ruffle organization	0.025	0.029	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.039	-10000	0	-0.26	1	1
PLD2	0.015	0.032	-10000	0	-10000	0	0
PIP5K1A	0.025	0.029	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.024	0.028	-10000	0	-10000	0	0
Rac1/GTP	-0.019	0.071	-10000	0	-0.32	13	13

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.035	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	-0.039	0.19	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.028	-9999	-0.48	1	1
CaM/Ca2+	-0.03	0.18	-9999	-10000	0	0
HIF1A	0.022	0	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
AKT1	-0.004	0.16	-9999	-10000	0	0
PLCG1	-0.039	0.19	-9999	-10000	0	0
NOS3	-0.002	0.16	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
mol:NO	-0.001	0.15	-9999	-10000	0	0
FLT1	0.033	0	-9999	-10000	0	0
PGF	-0.12	0.3	-9999	-0.8	49	49
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.038	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
eNOS/Hsp90	0.006	0.15	-9999	-10000	0	0
endothelial cell proliferation	-0.019	0.16	-9999	-10000	0	0
mol:Ca2+	-0.039	0.19	-9999	-10000	0	0
MAPK3	-0.019	0.17	-9999	-10000	0	0
MAPK1	-0.019	0.17	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.12	0.3	-9999	-0.8	49	49
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.065	0.24	-9999	-0.8	29	29
VEGFA homodimer	0.011	0.047	-9999	-0.8	1	1
VEGFR1 homodimer/VEGFA homodimer	0.033	0.032	-9999	-0.52	1	1
platelet activating factor biosynthetic process	-0.01	0.16	-9999	-10000	0	0
PI3K	-0.071	0.16	-9999	-10000	0	0
PRKCA	-0.029	0.18	-9999	-10000	0	0
PRKCB	-0.038	0.19	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	-0.055	0.2	-9999	-0.52	49	49
VEGFA	0.011	0.047	-9999	-0.8	1	1
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.039	0.19	-9999	-10000	0	0
RASA1	0.044	0	-9999	-10000	0	0
NRP2	0.011	0.047	-9999	-0.8	1	1
VEGFR1 homodimer	0.033	0	-9999	-10000	0	0
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.035	0.2	-9999	-0.73	7	7
PTPN11	0.013	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.07	0.16	-9999	-10000	0	0
mol:L-citrulline	-0.001	0.15	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.001	0.025	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.027	-9999	-10000	0	0
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.066	0.15	-9999	-10000	0	0
PDPK1	-0.019	0.17	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.027	-9999	-10000	0	0
mol:NADP	-0.001	0.15	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.025	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.033	0.032	-9999	-0.52	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.009	0.06	-9999	-0.72	2	2
CDC42/GTP	-0.02	0.07	-9999	-0.51	2	2
PLCG1	0.02	0.084	-9999	-0.53	2	2
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	-0.004	0.05	-9999	-0.61	2	2
cell migration	-0.02	0.069	-9999	-0.5	2	2
S1PR5	0.011	0.038	-9999	-0.64	1	1
S1PR4	-0.035	0.19	-9999	-0.8	18	18
MAPK3	0.02	0.084	-9999	-0.53	2	2
MAPK1	0.02	0.084	-9999	-0.53	2	2
S1P/S1P5/Gi	0.029	0.053	-9999	-0.47	1	1
GNAI1	0.011	0.038	-9999	-0.64	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.049	-9999	-0.49	3	3
RHOA	0.003	0.12	-9999	-0.45	20	20
S1P/S1P4/Gi	0.012	0.089	-9999	-0.56	2	2
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.004	0.11	-9999	-0.73	7	7
S1P/S1P4/G12/G13	-0.032	0.12	-9999	-0.49	20	20
GNA12	0.008	0.066	-9999	-0.8	2	2
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Aurora B 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
Condensin I complex	0.033	0.043	-9999	-10000	0	0
STMN1	0.024	0.052	-9999	-0.62	2	2
Aurora B/RasGAP/Survivin	0.017	0.082	-9999	-0.63	4	4
Chromosomal passenger complex/Cul3 protein complex	0.035	0.046	-9999	-0.4	2	2
BIRC5	0.005	0.094	-9999	-0.81	4	4
DES	-0.3	0.26	-9999	-0.55	155	155
Aurora C/Aurora B/INCENP	0.019	0.051	-9999	-0.45	3	3
Aurora B/TACC1	0.013	0.042	-9999	-0.47	2	2
Aurora B/PP2A	0.016	0.039	-9999	-0.61	1	1
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.018	0.01	-9999	-0.15	1	1
mitotic metaphase/anaphase transition	-0.001	0.001	-9999	-10000	0	0
NDC80	0.018	0.083	-9999	-0.62	5	5
Cul3 protein complex	-0.004	0.039	-9999	-0.4	3	3
KIF2C	0.01	0.034	-9999	-0.32	2	2
PEBP1	0.014	0.002	-9999	-10000	0	0
KIF20A	0.012	0.002	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.016	0.039	-9999	-0.61	1	1
SEPT1	0	0.1	-9999	-0.8	5	5
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.033	0.027	-9999	-0.38	1	1
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	0.021	0.022	-9999	-0.36	1	1
AURKB	0.019	0.049	-9999	-0.81	1	1
AURKC	0.009	0.06	-9999	-0.72	2	2
CDCA8	0.013	0.047	-9999	-0.81	1	1
cytokinesis	-0.019	0.05	-9999	-0.56	2	2
Aurora B/Septin1	0.019	0.082	-9999	-0.46	7	7
AURKA	-0.001	0.1	-9999	-0.8	5	5
INCENP	0.015	0.002	-9999	-10000	0	0
KLHL13	0.011	0.038	-9999	-0.64	1	1
BUB1	0.012	0.002	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.017	0.077	-9999	-0.59	4	4
EVI5	0.015	0.001	-9999	-10000	0	0
RhoA/GTP	-0.004	0.037	-9999	-0.44	2	2
SGOL1	0.013	0	-9999	-10000	0	0
CENPA	0.025	0.063	-9999	-0.51	3	3
NCAPG	0.013	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.016	0.039	-9999	-0.61	1	1
NCAPD2	0.005	0.081	-9999	-0.8	3	3
Aurora B/PP1-gamma	0.016	0.039	-9999	-0.61	1	1
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	0.005	0.081	-9999	-0.8	3	3
NPM1	0.011	0.027	-9999	-0.42	1	1
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.009	0.053	-9999	-0.64	2	2
mitotic prometaphase	0.001	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.039	-9999	-0.61	1	1
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.004	0.041	-9999	-0.48	2	2
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	0.011	0.027	-9999	-0.42	1	1
MYLK	0.017	0.043	-9999	-0.36	4	4
KIF23	0.014	0.001	-9999	-10000	0	0
VIM	0.026	0.037	-9999	-0.61	1	1
RACGAP1	0.014	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.011	0.027	-9999	-0.42	1	1
Chromosomal passenger complex	0.036	0.05	-9999	-0.51	2	2
Chromosomal passenger complex/EVI5	0.046	0.097	-9999	-0.73	3	3
TACC1	0.011	0.038	-9999	-0.64	1	1
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.004	0.044	-9999	-0.54	2	2
CRKL	0.033	0.054	-9999	-0.42	1	1
mol:PIP3	-0.024	0.003	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
PTK2B	0.013	0	-9999	-10000	0	0
RAPGEF1	0.04	0.052	-9999	-0.4	1	1
RANBP10	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.016	0.084	-9999	-0.44	11	11
MAP3K5	0.043	0.059	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.014	0.075	-9999	-0.48	4	4
AP1	-0.067	0.15	-9999	-0.41	49	49
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
apoptosis	-0.092	0.26	-9999	-0.69	49	49
STAT3 (dimer)	0.036	0.054	-9999	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.007	0.038	-9999	-10000	0	0
INPP5D	0.011	0.038	-9999	-0.64	1	1
CBL/CRK	0.041	0.045	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.013	0	-9999	-10000	0	0
PTEN	0.013	0	-9999	-10000	0	0
ELK1	0.001	0.022	-9999	-0.25	2	2
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.005	0.027	-9999	-10000	0	0
PAK1	0.007	0.027	-9999	-0.47	1	1
HGF/MET/RANBP10	-0.016	0.084	-9999	-0.44	11	11
HRAS	0.029	0.073	-9999	-0.64	1	1
DOCK1	0.04	0.052	-9999	-0.4	1	1
GAB1	0.028	0.049	-9999	-0.29	1	1
CRK	0.035	0.047	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.016	0.083	-9999	-0.5	7	7
JUN	0.013	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.008	0.043	-9999	-0.29	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
cell morphogenesis	0.066	0.059	-9999	-10000	0	0
GRB2/SHC	-0.006	0.035	-9999	-10000	0	0
FOS	-0.092	0.24	-9999	-0.64	49	49
GLMN	0	0	-9999	-10000	0	0
cell motility	0.001	0.022	-9999	-0.25	2	2
HGF/MET/MUC20	-0.016	0.085	-9999	-0.45	11	11
cell migration	-0.007	0.034	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
MET/RANBP10	-0.004	0.044	-9999	-0.54	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.03	0.056	-9999	-10000	0	0
MET/MUC20	-0.004	0.045	-9999	-0.55	2	2
RAP1B	0.046	0.055	-9999	-10000	0	0
RAP1A	0.047	0.049	-9999	-10000	0	0
HGF/MET/RANBP9	-0.016	0.084	-9999	-0.53	4	4
RAF1	0.037	0.069	-9999	-0.6	1	1
STAT3	0.037	0.054	-9999	-10000	0	0
cell proliferation	0.048	0.071	-9999	-10000	0	0
RPS6KB1	0.012	0.018	-9999	-10000	0	0
MAPK3	-0.005	0.019	-9999	-0.26	1	1
MAPK1	-0.005	0.019	-9999	-0.26	1	1
RANBP9	0.013	0	-9999	-10000	0	0
MAPK8	0.057	0.067	-9999	-0.5	2	2
SRC	0.037	0.053	-9999	-10000	0	0
PI3K	-0.006	0.035	-9999	-10000	0	0
MET/Glomulin	0.009	0.041	-9999	-0.49	2	2
SOS1	0.013	0	-9999	-10000	0	0
MAP2K1	0.044	0.065	-9999	-0.54	1	1
MET	0.009	0.06	-9999	-0.72	2	2
MAP4K1	0.036	0.062	-9999	-10000	0	0
PTK2	0.013	0	-9999	-10000	0	0
MAP2K2	0.044	0.065	-9999	-0.54	1	1
BAD	0.008	0.002	-9999	-10000	0	0
MAP2K4	0.05	0.056	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.007	0.04	-9999	-10000	0	0
INPPL1	0.013	0	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
SH3KBP1	0.013	0	-9999	-10000	0	0
HGS	0.017	0.043	-9999	-10000	0	0
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.008	0.12	-9999	-0.7	9	9
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
PTPRJ	0.013	0	-9999	-10000	0	0
NCK/PLCgamma1	0.025	0.044	-9999	-10000	0	0
PDPK1	-0.01	0.002	-9999	-10000	0	0
HGF/MET/SHIP	-0.017	0.092	-9999	-0.48	11	11

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.013	0.001	-9999	-10000	0	0
HDAC2	0.013	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.013	0.073	-9999	-0.41	10	10
forebrain development	-0.008	0.14	-9999	-0.46	7	7
GNAO1	0.008	0.06	-9999	-0.72	2	2
SMO/beta Arrestin2	0.003	0.084	-9999	-0.47	9	9
SMO	-0.006	0.11	-9999	-0.64	9	9
ARRB2	0.013	0.005	-9999	-10000	0	0
GLI3/SPOP	0.055	0.033	-9999	-10000	0	0
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.012	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0.005	0.013	-9999	-10000	0	0
GNAI1	0.01	0.038	-9999	-0.64	1	1
XPO1	0.015	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.051	0.097	-9999	-0.5	2	2
SAP30	0.013	0.001	-9999	-10000	0	0
mol:GDP	-0.006	0.11	-9999	-0.64	9	9
MIM/GLI2A	0.011	0.026	-9999	-10000	0	0
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.012	0.005	-9999	-10000	0	0
GLI2	0.031	0.059	-9999	-10000	0	0
GLI3	0.05	0.036	-9999	-10000	0	0
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.013	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.011	0.047	-9999	-0.8	1	1
Gi family/GTP	0.021	0.079	-9999	-0.49	3	3
SIN3B	0.013	0.001	-9999	-10000	0	0
SIN3A	0.013	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.058	0.038	-9999	-10000	0	0
GLI2/Su(fu)	0.038	0.065	-9999	-10000	0	0
FOXA2	-0.089	0.22	-9999	-0.64	41	41
neural tube patterning	-0.008	0.14	-9999	-0.46	7	7
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.024	0.047	-9999	-0.4	1	1
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	0.011	0.026	-9999	-10000	0	0
embryonic limb morphogenesis	-0.008	0.14	-9999	-0.46	7	7
SUFU	0.02	0.052	-9999	-0.44	1	1
LGALS3	0.013	0	-9999	-10000	0	0
catabolic process	0.068	0.05	-9999	-10000	0	0
GLI3A/CBP	-0.019	0.11	-9999	-0.35	1	1
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.009	0.14	-9999	-0.48	7	7
RAB23	0.008	0.066	-9999	-0.8	2	2
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.013	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.047	-9999	-0.4	1	1
GNAZ	-0.005	0.11	-9999	-0.73	7	7
RBBP4	0.013	0.001	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.035	0.055	-9999	-10000	0	0
STK36	0.015	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.028	0.072	-9999	-0.44	3	3
PTCH1	0.002	0.13	-9999	-10000	0	0
MIM/GLI1	-0.024	0.19	-9999	-0.64	9	9
CREBBP	-0.019	0.11	-9999	-0.35	1	1
Su(fu)/SIN3/HDAC complex	0.052	0.014	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.005	0.046	-9999	-0.53	1	1
BIRC5	0.003	0.093	-9999	-0.8	4	4
NFKBIA	0.028	0.039	-9999	-10000	0	0
CPEB1	-0.075	0.23	-9999	-0.67	39	39
AKT1	0.028	0.039	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.003	0.032	-9999	-10000	0	0
NDEL1/TACC3	-0.006	0.047	-9999	-0.46	2	2
GADD45A	0.011	0.047	-9999	-0.8	1	1
GSK3B	0.013	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.005	0.046	-9999	-0.53	1	1
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.013	0	-9999	-10000	0	0
TPX2	0.012	0.089	-9999	-0.62	6	6
TP53	-0.005	0.039	-9999	-0.32	3	3
DLG7	0.017	0.039	-9999	-0.3	3	3
AURKAIP1	0.013	0	-9999	-10000	0	0
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.006	0.05	-9999	-0.48	2	2
G2/M transition of mitotic cell cycle	-0.003	0.032	-9999	-10000	0	0
AURKA	0.02	0.046	-9999	-0.34	4	4
AURKB	-0.003	0.026	-9999	-0.28	2	2
CDC25B	-0.013	0.065	-9999	-0.55	1	1
G2/M transition checkpoint	-0.003	0.032	-9999	-10000	0	0
mRNA polyadenylation	-0.053	0.13	-9999	-0.39	38	38
Aurora A/CPEB	-0.053	0.13	-9999	-0.39	38	38
Aurora A/TACC1/TRAP/chTOG	-0.004	0.034	-9999	-10000	0	0
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	-0.005	0.046	-9999	-0.53	1	1
regulation of centrosome cycle	-0.006	0.046	-9999	-0.45	2	2
spindle assembly	-0.004	0.034	-9999	-10000	0	0
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.008	0.067	-9999	-0.55	4	4
CENPA	-0.005	0.034	-9999	-0.36	2	2
Aurora A/PP2A	-0.004	0.035	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.033	0.035	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.043	-9999	-0.32	3	3
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.003	0.032	-9999	-10000	0	0
mitotic prometaphase	0	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.046	-9999	-0.34	4	4
TACC1	0.011	0.038	-9999	-0.64	1	1
TACC3	0.008	0.066	-9999	-0.8	2	2
Aurora A/Antizyme1	-0.003	0.031	-9999	-10000	0	0
Aurora A/RasGAP	-0.004	0.035	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.002	0.03	-9999	-0.53	1	1
Importin alpha/Importin beta/TPX2	0.012	0.089	-9999	-0.61	6	6
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.022	0.079	-9999	-0.48	6	6
PAK1	0.011	0.047	-9999	-0.8	1	1
CKAP5	0.013	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.036	0.075	-9999	-10000	0	0
BAG4	0.013	0	-9999	-10000	0	0
BAD	0.03	0.028	-9999	-10000	0	0
NFKBIA	0.013	0	-9999	-10000	0	0
BIRC3	-0.024	0.17	-9999	-0.8	14	14
BAX	0.03	0.028	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.013	0.021	-9999	-0.095	3	3
IKBKB	0.043	0.072	-9999	-10000	0	0
MAP2K2	0.043	0.03	-9999	-10000	0	0
MAP2K1	0.043	0.03	-9999	-10000	0	0
SMPD1	0.019	0.021	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	-0.009	0.16	-9999	-0.62	5	5
MAP2K4	0.037	0.028	-9999	-10000	0	0
protein ubiquitination	0.045	0.073	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.048	0.033	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.037	0.03	-9999	-10000	0	0
CRADD	0.014	0	-9999	-10000	0	0
mol:ceramide	0.022	0.03	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.014	0	-9999	-10000	0	0
MAP3K1	0.03	0.029	-9999	-10000	0	0
TRADD	0.014	0	-9999	-10000	0	0
RELA/p50	0.013	0	-9999	-10000	0	0
MAPK3	0.045	0.03	-9999	-10000	0	0
MAPK1	0.045	0.03	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	-0.018	0.17	-9999	-0.44	37	37
KSR1	0.03	0.03	-9999	-10000	0	0
MAPK8	0.041	0.039	-9999	-0.35	1	1
TRAF2	0.008	0.066	-9999	-0.8	2	2
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.043	0.072	-9999	-10000	0	0
TNF R/SODD	0	0	-9999	-10000	0	0
TNF	-0.024	0.17	-9999	-0.76	15	15
CYCS	0.032	0.029	-9999	-10000	0	0
IKBKG	0.043	0.072	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.029	0.078	-9999	-0.42	3	3
RELA	0.013	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
AIFM1	0.032	0.029	-9999	-10000	0	0
TNF/TNF R/SODD	-0.024	0.11	-9999	-0.49	15	15
TNFRSF1A	0.013	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.021	-9999	-10000	0	0
NSMAF	0.036	0.074	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.004	0.08	-9999	-0.68	4	4

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.003	0.089	-10000	0	-0.67	5	5
oxygen homeostasis	0	0.017	-10000	0	-10000	0	0
TCEB2	0.013	0	-10000	0	-10000	0	0
TCEB1	0.011	0.047	-10000	0	-0.8	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.02	0.075	-10000	0	-10000	0	0
EPO	-0.015	0.26	-10000	0	-0.7	16	16
FIH (dimer)	0.012	0.017	-10000	0	-10000	0	0
APEX1	0.015	0.014	-10000	0	-10000	0	0
SERPINE1	-0.24	0.38	-10000	0	-0.86	17	17
FLT1	0.009	0.036	-10000	0	-10000	0	0
ADORA2A	0	0.22	-10000	0	-0.86	2	2
germ cell development	-0.004	0.23	-10000	0	-0.86	3	3
SLC11A2	0.003	0.22	-10000	0	-1	1	1
BHLHE40	0.003	0.22	-10000	0	-1	1	1
HIF1AN	0.012	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.054	0.098	-10000	0	-0.54	2	2
ETS1	0.025	0.066	-10000	0	-0.79	2	2
CITED2	-0.005	0.11	-10000	0	-1	3	3
KDR	0.007	0.052	-10000	0	-0.65	1	1
PGK1	0.003	0.22	-10000	0	-1	1	1
SIRT1	0.013	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	-0.007	0.25	-10000	0	-1.4	1	1
EPAS1	0.012	0.13	-10000	0	-0.43	5	5
SP1	0.022	0.003	-10000	0	-10000	0	0
ABCG2	-0.005	0.23	-10000	0	-0.88	3	3
EFNA1	0.002	0.23	-10000	0	-1.3	1	1
FXN	0.002	0.22	-10000	0	-0.99	1	1
POU5F1	-0.006	0.24	-10000	0	-0.91	3	3
neuron apoptosis	0.006	0.24	1.3	1	-10000	0	1
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	-0.049	0.22	-10000	0	-0.8	23	23
EGLN2	0.012	0.017	-10000	0	-10000	0	0
EGLN1	0.012	0.017	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.002	0.03	-10000	0	-0.53	1	1
VHL	0.013	0	-10000	0	-10000	0	0
ARNT	0.015	0.014	-10000	0	-10000	0	0
SLC2A1	-0.007	0.24	-10000	0	-0.9	7	7
TWIST1	-0.007	0.24	-10000	0	-0.83	7	7
ELK1	0.019	0.047	-10000	0	-0.8	1	1
HIF2A/ARNT/Cbp/p300	-0.045	0.09	-10000	0	-0.61	1	1
VEGFA	0.002	0.23	-10000	0	-0.99	2	2
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.062	0.018	-10000	0	-10000	0	0
NFATC2	0.034	0.047	-10000	0	-0.3	1	1
NFATC3	0.024	0.026	-10000	0	-0.43	1	1
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.015	0.076	-10000	0	-0.47	2	2
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	-0.042	0.11	-10000	0	-0.55	7	7
BCL2/BAX	-0.007	0.058	-10000	0	-0.51	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.001	0.003	-10000	0	-10000	0	0
BAX	0.013	0	-10000	0	-10000	0	0
MAPK14	0.014	0.002	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.021	0.072	-10000	0	-0.55	1	1
Calcineurin A alpha-beta B1/BCL2	0.004	0.08	-10000	0	-0.68	4	4
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.021	0.071	0.54	1	-10000	0	1
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.013	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	0.011	0.038	-10000	0	-0.64	1	1
MAP3K8	0.014	0.002	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.001	0.014	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.01	0.048	-10000	0	-10000	0	0
CABIN1	0.015	0.077	-10000	0	-0.48	2	2
CALM1	0.014	0.002	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.013	0	-10000	0	-10000	0	0
CAMK4	-0.04	0.2	-10000	0	-0.8	20	20
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.036	0.14	-10000	0	-0.61	18	18
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	0.01	0.053	-10000	0	-0.64	2	2
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0	0.019	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0	0.001	-10000	0	-10000	0	0
CASP3	0.014	0.002	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.002	0.018	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.046	0.013	-10000	0	-10000	0	0
PRKCB	-0.005	0.12	-10000	0	-0.78	7	7
PRKCE	0.013	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.029	0.024	-10000	0	-0.38	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.64	1	1
PRKCA	0.011	0.047	-10000	0	-0.8	1	1
PRKCG	-0.069	0.24	-10000	0	-0.8	29	29
PRKCQ	-0.001	0.1	-10000	0	-0.72	6	6
FKBP38/BCL2	-0.007	0.058	-10000	0	-0.51	4	4
EP300	0.014	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.064	0.033	-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	0.022	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.035	0.13	-10000	0	-0.53	20	20
NFATc/ERK1	0.067	0.017	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.042	0.12	-10000	0	-0.55	7	7
NR4A1	0.056	0.1	-10000	0	-0.61	6	6
GSK3B	0.014	0.002	-10000	0	-10000	0	0
positive T cell selection	0.024	0.026	-10000	0	-0.43	1	1
NFAT1/CK1 alpha	-0.007	0.026	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.014	0.002	-10000	0	-10000	0	0
AKAP5	-0.035	0.19	-10000	0	-0.8	18	18
MEF2D	0.014	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.066	0.019	-10000	0	-10000	0	0
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.004	0.08	-10000	0	-0.68	4	4

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.011	0.047	-9999	-0.8	1	1
Rac1/GDP	0.002	0.013	-9999	-10000	0	0
DOCK1	0.013	0	-9999	-10000	0	0
ITGA4	-0.014	0.15	-9999	-0.8	10	10
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.022	0.11	-9999	-0.6	11	11
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.099	-9999	-0.53	11	11
alpha4/beta7 Integrin/Paxillin	-0.017	0.088	-9999	-0.48	10	10
lamellipodium assembly	0.002	0.014	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
TLN1	0.011	0.047	-9999	-0.8	1	1
PXN	0.025	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.015	0.076	-9999	-10000	0	0
cell adhesion	-0.017	0.086	-9999	-10000	0	0
CRKL/CBL	-0.002	0.035	-9999	-0.61	1	1
alpha4/beta1 Integrin/Paxillin	-0.017	0.09	-9999	-0.48	11	11
ITGB1	0.011	0.047	-9999	-0.8	1	1
ITGB7	0.011	0.038	-9999	-0.64	1	1
ARF6/GDP	0.002	0.013	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.066	0.16	-9999	-0.9	2	2
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.078	0.25	-9999	-0.78	35	35
alpha4/beta1 Integrin/Paxillin/Talin	-0.018	0.087	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.016	0.084	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
mol:GDP	0.016	0.083	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.018	0.087	-9999	-10000	0	0
Rac1/GTP	0.002	0.015	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.017	0.14	-9999	-0.64	14	14
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.018	0.05	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.011	0.047	-9999	-0.8	1	1
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.011	0.047	-9999	-0.8	1	1
p38 alpha/TAB1	-0.02	0.045	-9999	-10000	0	0
PRKG1	-0.008	0.12	-9999	-0.71	9	9
DUSP8	0.013	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.028	0.07	-9999	-0.42	5	5
apoptosis	-0.02	0.043	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.041	0.18	-9999	-0.64	25	25
PAK1	0.011	0.047	-9999	-0.8	1	1
SRC	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.02	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.019	0.1	-9999	-0.39	5	5
BLK	-0.12	0.3	-9999	-0.77	53	53
HCK	0.004	0.084	-9999	-0.72	4	4
MAP2K3	0.011	0.038	-9999	-0.64	1	1
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.011	0.047	-9999	-0.8	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.028	0.073	-9999	-10000	0	0
positive regulation of innate immune response	0.027	0.11	-9999	-0.41	4	4
LCK	-0.014	0.15	-9999	-0.8	10	10
p38alpha-beta/MKP7	0.032	0.1	-9999	-10000	0	0
p38alpha-beta/MKP5	0.031	0.11	-9999	-10000	0	0
PGK/cGMP	-0.016	0.093	-9999	-0.54	9	9
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.007	0.14	-9999	-0.51	5	5
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.023	0.16	-9999	-0.78	13	13

×

TCGA08_rtk_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
PDGFRA	-0.003	0.11	-9999	-0.69	7	7
HRAS	0.013	0	-9999	-10000	0	0
EGFR	-0.014	0.15	-9999	-0.8	10	10
AKT	0.037	0.051	-9999	-0.3	6	6
FOXO3	0.013	0	-9999	-10000	0	0
AKT1	0.013	0	-9999	-10000	0	0
FOXO1	0.013	0	-9999	-10000	0	0
AKT3	-0.003	0.11	-9999	-0.8	6	6
FOXO4	0.009	0.053	-9999	-0.64	2	2
MET	0.009	0.06	-9999	-0.72	2	2
PIK3CA	0.013	0	-9999	-10000	0	0
PIK3CB	0.013	0	-9999	-10000	0	0
NRAS	0.013	0	-9999	-10000	0	0
PIK3CG	-0.025	0.17	-9999	-0.77	15	15
PIK3R3	0.011	0.038	-9999	-0.64	1	1
PIK3R2	0.013	0	-9999	-10000	0	0
NF1	0.013	0	-9999	-10000	0	0
RAS	0.019	0.043	-9999	-10000	0	0
ERBB2	0.008	0.066	-9999	-0.8	2	2
proliferation/survival/translation	-0.031	0.027	-9999	-10000	0	0
PI3K	0.025	0.052	-9999	-0.22	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
KRAS	0.013	0	-9999	-10000	0	0
FOXO	0.048	0.03	-9999	-0.17	1	1
AKT2	0.013	0	-9999	-10000	0	0
PTEN	0.013	0	-9999	-10000	0	0

×

Class I PI3K signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0	-9999	-10000	0	0
DAPP1	0.008	0.098	-9999	-0.39	2	2
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.01	0.17	-9999	-0.75	9	9
mol:DAG	0.026	0.09	-9999	-0.31	8	8
HRAS	0.014	0	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
ARF5/GDP	0.042	0.036	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
PLCG1	0.013	0	-9999	-10000	0	0
ARF5	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
RAP1A/GTP	0	0	-9999	-10000	0	0
ADAP1	0	0	-9999	-10000	0	0
ARAP3	0	0	-9999	-10000	0	0
INPPL1	0.013	0	-9999	-10000	0	0
PREX1	0.013	0	-9999	-10000	0	0
ARHGEF6	0.009	0.053	-9999	-0.64	2	2
ARHGEF7	0.013	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
NRAS	0.014	0	-9999	-10000	0	0
FYN	0.011	0.047	-9999	-0.8	1	1
ARF6	0.013	0	-9999	-10000	0	0
FGR	0.011	0.047	-9999	-0.8	1	1
mol:Ca2+	0.026	0.049	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.007	0.065	-9999	-0.64	3	3
ZAP70	-0.022	0.16	-9999	-0.74	14	14
mol:IP3	0.029	0.066	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
ARF1/GDP	0.042	0.036	-9999	-10000	0	0
RhoA/GDP	-0.001	0.007	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.056	0.2	-9999	-0.64	32	32
actin cytoskeleton reorganization	0.067	0.031	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PLEKHA2	0.031	0.024	-9999	-0.39	1	1
RAC1	0.013	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.029	0.18	-9999	-0.6	18	18
BLK	-0.12	0.3	-9999	-0.77	53	53
PDPK1	0.013	0	-9999	-10000	0	0
CYTH1	0	0	-9999	-10000	0	0
HCK	0.004	0.084	-9999	-0.72	4	4
CYTH3	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
KRAS	0.014	0	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.002	0.027	-9999	-0.47	1	1
SGK1	-0.002	0.029	-9999	-0.51	1	1
INPP5D	0.011	0.038	-9999	-0.64	1	1
mol:GDP	0.036	0.038	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
SYK	0.011	0.038	-9999	-0.64	1	1
ARF6/GDP	-0.001	0.007	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0	-9999	-10000	0	0
VAV1	0.003	0.083	-9999	-0.64	5	5
mol:PI-3-4-P2	0.023	0.028	-9999	-0.47	1	1
RAS family/GTP/PI3K Class I	0	0	-9999	-10000	0	0
PLEKHA1	0.031	0.024	-9999	-0.39	1	1
Rac1/GDP	0.042	0.036	-9999	-10000	0	0
LAT	-0.008	0.13	-9999	-0.8	8	8
Rac1/GTP	0.037	0.052	-9999	-10000	0	0
ITK	-0.015	0.073	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.12	-9999	-0.44	9	9
LCK	-0.014	0.15	-9999	-0.8	10	10
BTK	-0.001	0.024	-9999	-0.42	1	1

×

Arf6 trafficking 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
SLC2A4	-0.27	0.32	-10000	0	-0.64	133	133
CLTC	0.034	0.017	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.029	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.002	0.028	-10000	0	-0.49	1	1
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.03	0.018	-10000	0	-10000	0	0
CPE	0.015	0.055	-10000	0	-0.54	3	3
CTNNB1	0.011	0.038	-10000	0	-0.64	1	1
membrane fusion	0	0	-10000	0	-10000	0	0
CTNND1	0.033	0.028	-10000	0	-0.45	1	1
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0.007	-10000	0	-10000	0	0
TSHR	0.008	0.078	-10000	0	-0.54	6	6
INS	0.013	0.002	-10000	0	-10000	0	0
BIN1	0	0.1	-10000	0	-0.8	5	5
mol:Choline	0	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.032	-10000	0	-0.54	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.028	-10000	0	-0.48	1	1
JUP	0.03	0.018	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.008	0.062	-10000	0	-0.49	5	5
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.029	0.023	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.047	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.029	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.027	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.026	0.011	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.015	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.047	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	0.028	-10000	0	-0.45	1	1
NME1	0.019	0.032	-10000	0	-0.54	1	1
clathrin coat assembly	0.034	0.017	-10000	0	-10000	0	0
IL2RA	0.001	0.082	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.12	0.14	-10000	0	-0.51	1	1
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.036	0.007	-10000	0	-10000	0	0
SDC1	0.031	0.011	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.032	-10000	0	-0.54	1	1
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.003	0.03	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
endocytosis	0.008	0.062	0.48	5	-10000	0	5
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.013	0.098	-10000	0	-0.58	1	1
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.013	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.025	0.029	-10000	0	-0.48	1	1
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.024	0.077	-10000	0	-10000	0	0
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.027	-10000	0	-10000	0	0

×

Canonical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.09	0.024	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	0	0	-9999	-10000	0	0
NFKBIA	0.051	0	-9999	-10000	0	0
BIRC2	-0.003	0.11	-9999	-0.8	6	6
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.004	0.026	-9999	-10000	0	0
IKK complex/A20	-0.02	0.077	-9999	-10000	0	0
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.051	0.031	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.003	0.019	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.013	0	-9999	-10000	0	0
NFKB1	0.017	0	-9999	-10000	0	0
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	-0.012	0.085	-9999	-0.61	6	6
ATM	0.013	0	-9999	-10000	0	0
TNF/TNFR1A	-0.028	0.12	-9999	-0.57	15	15
TRAF6	0.013	0	-9999	-10000	0	0
PRKCA	0.011	0.047	-9999	-0.8	1	1
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.76	15	15
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.051	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.003	0.022	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.004	0.029	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.002	0.027	-9999	-0.48	1	1
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC5	0	0	-9999	-10000	0	0
GATA2/HDAC5	-0.004	0.05	-9999	-0.61	2	2
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.024	0.17	-9999	-0.79	14	14
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
GATA2	0.008	0.066	-9999	-0.8	2	2
HDAC4/RFXANK	0	0	-9999	-10000	0	0
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.013	0	-9999	-10000	0	0
HDAC5	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.002	0.035	-9999	-0.61	1	1
Histones	0.032	0.052	-9999	-10000	0	0
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	-0.04	0.2	-9999	-0.8	20	20
Tubulin/HDAC6	-0.002	0.03	-9999	-0.53	1	1
SUMO1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.011	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.002	0.035	-9999	-0.61	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.034	0.13	-9999	-0.52	20	20
HDAC4/ER alpha	-0.032	0.13	-9999	-0.56	17	17
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.032	0.052	-9999	-10000	0	0
cell motility	-0.002	0.03	-9999	-0.53	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.013	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.029	0.18	-9999	-0.75	17	17
HDAC6/HDAC11	-0.002	0.027	-9999	-0.47	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.002	0.11	-9999	-0.75	6	6
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.008	0.057	-9999	-0.45	4	4
GNG2	0.011	0.047	-9999	-0.8	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.011	0.047	-9999	-0.8	1	1
HDAC11	0.011	0.038	-9999	-0.64	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.013	0	-9999	-10000	0	0
nuclear import	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.012	0.007	-10000	0	-10000	0	0
BUB1B	0.023	0.023	-10000	0	-10000	0	0
PLK1	0.018	0.02	-10000	0	-0.16	1	1
PLK1S1	0.015	0.018	-10000	0	-0.17	2	2
KIF2A	0.026	0.018	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.018	0.02	-10000	0	-0.16	1	1
GOLGA2	0.013	0	-10000	0	-10000	0	0
Hec1/SPC24	0.015	0.091	-10000	0	-0.47	10	10
WEE1	0.023	0.024	-10000	0	-10000	0	0
cytokinesis	0.034	0.021	-10000	0	-10000	0	0
PP2A-alpha B56	0	0.007	-10000	0	-10000	0	0
AURKA	0.014	0.028	-10000	0	-0.19	5	5
PICH/PLK1	0.027	0.076	-10000	0	-0.38	10	10
CENPE	0.026	0.018	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.026	0.018	-10000	0	-10000	0	0
PPP2CA	0.013	0	-10000	0	-10000	0	0
FZR1	0.013	0	-10000	0	-10000	0	0
TPX2	0.012	0.029	-10000	0	-0.18	6	6
PAK1	0.01	0.047	-10000	0	-0.8	1	1
SPC24	-0.003	0.11	-10000	0	-0.8	6	6
FBXW11	0.013	0	-10000	0	-10000	0	0
CLSPN	0.012	0.034	-10000	0	-0.2	7	7
GORASP1	0.013	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.017	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.01	0.01	-10000	0	-0.07	1	1
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.013	5	5
STAG2	0.013	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.007	-10000	0	-10000	0	0
spindle elongation	0.018	0.02	-10000	0	-0.16	1	1
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	-0.001	0.009	-10000	0	-10000	0	0
TPT1	0.016	0.01	-10000	0	-10000	0	0
CDC25C	0.015	0.028	-10000	0	-0.24	3	3
CDC25B	-0.013	0.14	-10000	0	-0.8	10	10
SGOL1	0.012	0.007	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.013	0.069	-10000	0	-0.39	10	10
CDC14B	0.011	0.029	-10000	0	-0.49	1	1
CDC20	0.003	0.093	-10000	0	-0.8	4	4
PLK1/PBIP1	-0.005	0.04	-10000	0	-0.48	2	2
mitosis	0	0.005	0.04	5	-0.021	2	7
FBXO5	0.022	0.018	-10000	0	-10000	0	0
CDC2	0.001	0.003	-10000	0	-0.016	10	10
NDC80	0.003	0.093	-10000	0	-0.8	4	4
metaphase plate congression	0.017	0.012	-10000	0	-10000	0	0
ERCC6L	-0.012	0.065	-10000	0	-0.36	10	10
NLP/gamma Tubulin	0.015	0.011	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.016	0.01	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.013	0.001	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.031	0.017	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.009	-10000	0	-10000	0	0
RAB1A	0.013	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.018	0.044	-10000	0	-0.46	2	2
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.019	-10000	0	-10000	0	0
microtubule-based process	0.024	0.018	-10000	0	-10000	0	0
Golgi organization	0.018	0.02	-10000	0	-0.16	1	1
Cohesin/SA2	-0.002	0.012	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	0.013	0	-10000	0	-10000	0	0
APC/C/CDC20	0.017	0.064	-10000	0	-0.52	4	4
PPP2R1A	0.013	0	-10000	0	-10000	0	0
chromosome segregation	-0.005	0.04	-10000	0	-0.47	2	2
PRC1	0.013	0	-10000	0	-10000	0	0
ECT2	0.021	0.053	-10000	0	-0.48	3	3
C13orf34	0.019	0.043	-10000	0	-0.46	2	2
NUDC	0.017	0.012	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.023	0.022	-10000	0	-10000	0	0
spindle assembly	0.018	0.016	-10000	0	-10000	0	0
spindle stabilization	0.015	0.018	-10000	0	-0.17	2	2
APC/C/HCDH1	0.017	0.025	-10000	0	-0.41	1	1
MKLP2/PLK1	0.024	0.018	-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	0.013	0	-10000	0	-10000	0	0
ROCK2	0.024	0.03	-10000	0	-0.44	1	1
TUBG1	0.016	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.013	0.068	-10000	0	-0.38	10	10
MLF1IP	0.009	0.052	-10000	0	-0.63	2	2
INCENP	0.013	0.001	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.007	0.04	0.42	1	-10000	0	1
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.049	-10000	0	-0.49	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.009	0.06	-10000	0	-0.72	2	2
RhoA/GTP	-0.007	0.041	-10000	0	-0.43	1	1
negative regulation of cAMP metabolic process	0.029	0.053	-10000	0	-0.47	1	1
GNAZ	-0.004	0.11	-10000	0	-0.73	7	7
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.008	0.066	-10000	0	-0.8	2	2
S1PR5	0.011	0.038	-10000	0	-0.64	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.029	0.053	-10000	0	-0.47	1	1
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.011	0.038	-10000	0	-0.64	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.028	0.13	-9999	-0.61	14	14
AKT1	0.093	0.038	-9999	-10000	0	0
PTK2B	0.038	0.11	-9999	-0.62	1	1
VEGFR2 homodimer/Frs2	0.031	0.066	-9999	-0.54	4	4
CAV1	-0.065	0.24	-9999	-0.8	29	29
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.008	0.062	-9999	-0.55	1	1
endothelial cell proliferation	0.099	0.054	-9999	-10000	0	0
mol:Ca2+	0.058	0.046	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.004	0.039	-9999	-10000	0	0
RP11-342D11.1	0.049	0.046	-9999	-10000	0	0
CDH5	0.011	0.047	-9999	-0.8	1	1
VEGFA homodimer	-0.002	0.027	-9999	-0.48	1	1
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.009	0.06	-9999	-0.72	2	2
HRAS/GDP	-0.003	0.033	-9999	-10000	0	0
SH2D2A	-0.086	0.27	-9999	-0.8	37	37
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.005	0.035	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.061	0.16	-9999	-0.59	2	2
VEGFR1 homodimer	0.013	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.004	0.037	-9999	-10000	0	0
GRB10	0.057	0.061	-9999	-0.71	1	1
PTPN11	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.011	0.047	-9999	-0.8	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.006	0.047	-9999	-10000	0	0
HRAS	0.013	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.043	0.06	-9999	-0.48	1	1
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.005	0.081	-9999	-0.8	3	3
oxygen and reactive oxygen species metabolic process	-0.003	0.039	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0	0.1	-9999	-0.8	5	5
Nck/Pak	-0.002	0.035	-9999	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.005	0.05	-9999	-10000	0	0
mol:GDP	-0.003	0.036	-9999	-10000	0	0
mol:NADP	0.079	0.047	-9999	-10000	0	0
eNOS/Hsp90	0.081	0.045	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.059	0.046	-9999	-10000	0	0
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.053	-9999	-0.64	2	2
VEGFA	0.013	0.047	-9999	-0.8	1	1
VEGFC	-0.088	0.27	-9999	-0.8	38	38
FAK1/Vinculin	0.064	0.073	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.023	0.099	-9999	-0.66	1	1
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.023	0.02	-9999	-10000	0	0
mol:L-citrulline	0.079	0.047	-9999	-10000	0	0
ITGAV	0.006	0.076	-9999	-0.75	3	3
PIK3CA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.058	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.044	-9999	-10000	0	0
VEGFR2/3 heterodimer	0.028	0.09	-9999	-1.1	1	1
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.062	0.047	-9999	-10000	0	0
VEGFR2 homodimer	0.037	0.043	-9999	-0.7	1	1
FLT1	0.013	0	-9999	-10000	0	0
NEDD4	0.016	0.004	-9999	-10000	0	0
MAPK3	0.062	0.049	-9999	-10000	0	0
MAPK1	0.062	0.049	-9999	-10000	0	0
VEGFA145/NRP2	-0.004	0.049	-9999	-0.61	2	2
VEGFR1/2 heterodimer	0.037	0.037	-9999	-0.61	1	1
KDR	0.037	0.043	-9999	-0.7	1	1
VEGFA165/NRP1/VEGFR2 homodimer	-0.005	0.046	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.064	0.049	-9999	-10000	0	0
PI3K	-0.004	0.034	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.004	0.042	-9999	-0.55	1	1
FES	0.059	0.047	-9999	-10000	0	0
GAB1	-0.003	0.032	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.004	0.042	-9999	-0.55	1	1
CTNNB1	0.011	0.038	-9999	-0.64	1	1
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.043	0.12	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.004	0.042	-9999	-0.55	1	1
PI3K/GAB1	0.094	0.039	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.009	0.059	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.068	0.18	-9999	-1.4	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.059	0.047	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.06	0.16	-9999	-0.59	2	2
PTK2	0.059	0.077	-9999	-10000	0	0
EDG1	0.049	0.046	-9999	-10000	0	0
mol:DAG	0.059	0.046	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.037	-9999	-10000	0	0
MAP2K3	0.063	0.057	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.005	0.056	-9999	-0.72	1	1
PLCG1	0.059	0.047	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.006	0.046	-9999	-10000	0	0
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.004	0.042	-9999	-0.55	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.004	0.042	-9999	-0.55	1	1
cell migration	0.087	0.066	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.032	-9999	-10000	0	0
FYN	0.011	0.047	-9999	-0.8	1	1
VEGFB/NRP1	-0.004	0.038	-9999	-10000	0	0
mol:NO	0.079	0.047	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.003	0.033	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.056	0.062	-9999	-0.71	1	1
VHL	0.013	0	-9999	-10000	0	0
ITGB3	-0.017	0.15	-9999	-0.76	12	12
NOS3	0.081	0.051	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.007	0.058	-9999	-0.59	2	2
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.064	0.052	-9999	-10000	0	0
PRKCB	0.055	0.082	-9999	-10000	0	0
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.048	0.046	-9999	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	-0.004	0.042	-9999	-0.55	1	1
VEGFA165/NRP2	-0.004	0.049	-9999	-0.61	2	2
MAPKKK cascade	-0.004	0.045	-9999	-10000	0	0
NRP2	0.011	0.047	-9999	-0.8	1	1
VEGFC homodimer	-0.088	0.27	-9999	-0.8	38	38
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.064	0.073	-9999	-10000	0	0
MAP3K13	0.056	0.056	-9999	-10000	0	0
PDPK1	0.085	0.039	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.052	0.03	-10000	0	-0.41	1	1
adherens junction organization	0.043	0.052	-10000	0	-0.5	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.044	0.081	-10000	0	-10000	0	0
FMN1	0.034	0.078	-10000	0	-0.6	2	2
mol:IP3	-0.002	0.027	-10000	0	-0.43	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.037	0.047	-10000	0	-0.66	1	1
CTNNB1	0.011	0.037	-10000	0	-0.64	1	1
AKT1	0.05	0.034	-10000	0	-0.46	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.042	0.059	-10000	0	-0.73	1	1
CTNND1	0.015	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.044	-10000	0	-0.6	1	1
VASP	0.044	0.045	-10000	0	-0.62	1	1
ZYX	0.044	0.045	-10000	0	-0.62	1	1
JUB	0.044	0.045	-10000	0	-0.62	1	1
EGFR(dimer)	0.028	0.094	-10000	0	-0.44	11	11
E-cadherin/beta catenin-gamma catenin	-0.005	0.052	-10000	0	-0.73	1	1
mol:PI-3-4-5-P3	-0.003	0.031	-10000	0	-0.49	1	1
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
PI3K	-0.003	0.032	-10000	0	-0.5	1	1
FYN	0.052	0.053	-10000	0	-0.6	1	1
mol:Ca2+	-0.002	0.026	-10000	0	-0.42	1	1
JUP	0.011	0.037	-10000	0	-0.64	1	1
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.002	0.027	-10000	0	-0.43	1	1
CDH1	0.009	0.053	-10000	0	-0.64	2	2
RhoA/GDP	0.044	0.081	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.044	0.044	-10000	0	-0.6	1	1
SRC	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	-0.014	0.15	-10000	0	-0.8	10	10
CASR	0.044	0.053	-10000	0	-0.4	4	4
RhoA/GTP	-0.002	0.023	-10000	0	-0.38	1	1
AKT2	0.05	0.034	-10000	0	-0.46	1	1
actin cable formation	0.041	0.076	-10000	0	-0.57	2	2
apoptosis	0.002	0.028	0.44	1	-10000	0	1
CTNNA1	0.015	0.001	-10000	0	-10000	0	0
mol:GDP	0.037	0.086	-10000	0	-0.4	11	11
PIP5K1A	0.044	0.045	-10000	0	-0.62	1	1
PLCG1	-0.002	0.027	-10000	0	-0.44	1	1
Rac1/GTP	-0.016	0.076	-10000	0	-0.56	1	1
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.005	0.054	-9999	-0.76	1	1
E-cadherin/beta catenin	-0.005	0.046	-9999	-0.47	3	3
CTNNB1	0.011	0.038	-9999	-0.64	1	1
JUP	0.011	0.038	-9999	-0.64	1	1
CDH1	0.009	0.053	-9999	-0.64	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.011	0.038	-9999	-0.64	1	1
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.045	0.015	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0.017	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.023	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.017	-9999	-10000	0	0
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.021	0.022	-9999	-0.35	1	1
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.006	0.054	-9999	-0.47	4	4
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	0.007	0.065	-9999	-0.64	3	3
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.013	0	-9999	-10000	0	0
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.005	0.046	-10000	0	-0.47	3	3
ATM	0.013	0	-10000	0	-10000	0	0
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.013	0	-10000	0	-10000	0	0
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.028	0	-10000	0	-10000	0	0
protein ubiquitination	-0.005	0.04	-10000	0	-0.44	1	1
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.013	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.004	0.038	-10000	0	-0.56	1	1
FANCF	0.009	0.053	-10000	0	-0.64	2	2
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.011	0.047	-10000	0	-0.8	1	1
CDK2/Cyclin E1	-0.002	0.035	-10000	0	-0.61	1	1
FANCG	0.008	0.066	-10000	0	-0.8	2	2
BRCA1/BACH1/BARD1	-0.005	0.046	-10000	0	-0.47	3	3
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	0.011	0.047	-10000	0	-0.8	1	1
DNA repair	0.074	0.056	-10000	0	-0.49	1	1
BRCA1/BARD1/ubiquitin	-0.005	0.046	-10000	0	-0.47	3	3
BARD1/DNA-PK	-0.003	0.035	-10000	0	-10000	0	0
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.005	0.046	0.47	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.041	0.03	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.039	-10000	0	-0.4	3	3
BRCA1/BARD1/P53	-0.007	0.049	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.004	0.039	-10000	0	-0.4	3	3
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	0.007	0.065	-10000	0	-0.64	3	3
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.004	0.039	-10000	0	-0.4	3	3
BRCA1/BARD1/UbcH7	-0.004	0.039	-10000	0	-0.4	3	3
BRCA1/BARD1/RAD51/PCNA	-0.005	0.044	-10000	0	-0.48	1	1
BARD1/DNA-PK/P53	-0.006	0.045	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.005	0.046	-10000	0	-0.47	3	3
BRCA1/BARD1/CTIP	-0.003	0.035	-10000	0	-10000	0	0
FA complex	0.039	0.041	-10000	0	-0.5	1	1
BARD1/EWS	-0.005	0.046	-10000	0	-0.47	3	3
RBBP8	0.025	0	-10000	0	-10000	0	0
TP53	0.007	0.065	-10000	0	-0.64	3	3
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.007	0.049	-10000	0	-10000	0	0
BRCA1/BARD1	-0.005	0.041	-10000	0	-0.44	1	1
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.005	0.047	-10000	0	-0.48	3	3
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.011	0.047	-10000	0	-0.8	1	1
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.005	0.046	-10000	0	-0.47	3	3
EWSR1	0.013	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLK2	0.013	-9999	-9999
PLK4	0.013	-9999	-9999
regulation of centriole replication	0.025	-9999	-9999

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.004	0.044	-9999	-0.44	3	3
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.001	0.012	-9999	-10000	0	0
AURKB	0.011	0.047	-9999	-0.8	1	1
AURKC	0.009	0.06	-9999	-0.72	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.081	0.094	-10000	0	-0.41	1	1
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.057	0.14	0.3	6	-0.45	1	7
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.018	0.14	-10000	0	-0.8	10	10
PRKCI	0.013	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.035	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.038	-10000	0	-0.64	1	1
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.05	0.014	-10000	0	-10000	0	0
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	-0.064	0.15	0.3	6	-0.51	1	7
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.028	0	-10000	0	-10000	0	0
SFN	0.011	0.038	-10000	0	-0.64	1	1
LNPEP	0.013	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
GBL	0	0	-9999	-9999
MKNK1	0.013	0	-9999	-9999
mol:PIP3	0	0	-9999	-9999
FRAP1	0.017	0	-9999	-9999
AKT1	0	0	-9999	-9999
INSR	0.013	0	-9999	-9999
Insulin Receptor/Insulin	0	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-9999	-9999
TSC2	0.013	0	-9999	-9999
RHEB/GDP	0	0	-9999	-9999
TSC1	0.014	0	-9999	-9999
Insulin Receptor/IRS1	0.017	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
EIF3A	0.013	0	-9999	-9999
RPS6KB1	0.031	0	-9999	-9999
MAP3K5	0.011	0	-9999	-9999
PIK3R1	0.014	0	-9999	-9999
apoptosis	0.011	0	-9999	-9999
mol:LY294002	0	0	-9999	-9999
EIF4B	0.037	0	-9999	-9999
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1	0	0	-9999	-9999
KIAA1303	0	0	-9999	-9999
PI3K	0.026	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL	0.035	0	-9999	-9999
FKBP1A	0.014	0	-9999	-9999
RHEB/GTP	0	0	-9999	-9999
mol:Amino Acids	0	0	-9999	-9999
FKBP12/Rapamycin	0	0	-9999	-9999
PDPK1	0	0	-9999	-9999
EIF4E	0.013	0	-9999	-9999
ASK1/PP5C	0.023	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0	-9999	-9999
TSC1/TSC2	0	0	-9999	-9999
tumor necrosis factor receptor activity	0	0	-9999	-9999
RPS6	0.013	0	-9999	-9999
PPP5C	0.013	0	-9999	-9999
EIF4G1	0.013	0	-9999	-9999
IRS1	0.009	0	-9999	-9999
INS	0	0	-9999	-9999
PTEN	0.013	0	-9999	-9999
PDK2	0	0	-9999	-9999
EIF4EBP1	0.009	0.039	-9999	-9999
PIK3CA	0.014	0	-9999	-9999
PPP2R5D	0.024	0	-9999	-9999
peptide biosynthetic process	0.019	0	-9999	-9999
RHEB	0.014	0	-9999	-9999
EIF4A1	0.013	0	-9999	-9999
mol:Rapamycin	0	0	-9999	-9999
EEF2	0.019	0	-9999	-9999
eIF4E/4E-BP1	0.016	0.034	-9999	-9999

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.041	0	-9999	-10000	0	0
CDKN1A	0.041	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.013	0	-9999	-10000	0	0
FOXO3	0.041	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.013	0	-9999	-10000	0	0
AKT3	0.011	0.052	-9999	-0.36	6	6
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.039	0.028	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.013	0	-9999	-10000	0	0
RAF1	0.013	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.041	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
AKT1/RAF1	0.04	0	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.041	0	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
TBC1D4	0.027	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
MAPKAP1	0.013	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.048	0.009	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0
AKT1S1	0.041	0	-9999	-10000	0	0
CASP9	0.041	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.047	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0	-9999	-10000	0	0
CHUK	0.041	0	-9999	-10000	0	0
BAD/BCL-XL	0.054	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.019	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.064	0.014	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
MDM2	0.041	0	-9999	-10000	0	0
MAPKKK cascade	-0.039	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0	-9999	-10000	0	0
TSC1/TSC2	0.048	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
glucose import	-0.14	0.19	-9999	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.035	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.14	0.19	-9999	-10000	0	0
GSK3A	0.041	0	-9999	-10000	0	0
FOXO1	0.041	0	-9999	-10000	0	0
GSK3B	0.041	0	-9999	-10000	0	0
SFN	0.011	0.038	-9999	-0.64	1	1
G1/S transition of mitotic cell cycle	0.048	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.052	0.014	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
KPNA1	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
RHEB	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-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	0.085	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.015	0.065	-9999	-10000	0	0
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.008	0.037	-9999	-10000	0	0
YY1/LSF	0.021	0.057	-9999	-10000	0	0
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.015	0.064	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.01	0.045	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	0.028	0.063	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	-0.01	0.045	-9999	-10000	0	0
NuRD/MBD3 Complex	0.052	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.057	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.008	0.066	-9999	-0.8	2	2
GATA1	0.011	0.005	-9999	-10000	0	0
Mad/Max	-0.002	0.027	-9999	-0.47	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.063	0.002	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.013	0	-9999	-10000	0	0
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	0.018	0.058	-9999	-10000	0	0
KAT2B	-0.015	0.13	-9999	-0.64	13	13
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.047	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.013	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	-0.017	0.054	-9999	-10000	0	0
YY1/HDAC2	0.021	0.057	-9999	-10000	0	0
YY1/HDAC1	0.021	0.057	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.052	0	-9999	-10000	0	0
PPARG	-0.14	0.17	-9999	-0.56	8	8
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.01	0.045	-9999	-10000	0	0
MBD3L2	-0.002	0.046	-9999	-0.8	1	1
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.055	0.012	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.018	0.058	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.019	0.068	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.011	0.038	-9999	-0.64	1	1
STAT3	0.028	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.009	0.044	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.009	0.044	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.028	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.058	-9999	-10000	0	0
histone deacetylation	0.052	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.009	0.039	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	-0.013	0.064	-9999	-0.58	2	2
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	-0.01	0.045	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.028	0.12	-9999	-0.57	15	15
SIN3/HDAC complex/Mad/Max	0.051	0.013	-9999	-10000	0	0
NuRD Complex	0.061	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.008	0.036	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	0	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.76	15	15
negative regulation of cell growth	0.051	0.013	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.052	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.016	0.069	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.05	0	-9999	-10000	0	0
TFCP2	0.013	0	-9999	-10000	0	0
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	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	0.043	0.012	-9999	-10000	0	0
PLK1	0.12	0.1	-9999	-0.74	1	1
CDKN1B	0.15	0.046	-9999	-10000	0	0
FOXO3	0.12	0.1	-9999	-0.57	1	1
KAT2B	-0.001	0.13	-9999	-0.63	13	13
FOXO1/SIRT1	0.009	0.024	-9999	-10000	0	0
CAT	0.11	0.12	-9999	-1.2	1	1
CTNNB1	0.011	0.038	-9999	-0.64	1	1
AKT1	0.03	0.01	-9999	-10000	0	0
FOXO1	0.046	0.009	-9999	-10000	0	0
MAPK10	0.028	0.08	-9999	-0.45	1	1
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.049	-9999	-10000	0	0
response to oxidative stress	0.018	0.01	-9999	-10000	0	0
FOXO3A/SIRT1	0.003	0.069	-9999	-0.54	1	1
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.016	0.001	-9999	-10000	0	0
BCL2L11	0.044	0.024	-9999	-10000	0	0
FOXO1/SKP2	0.047	0.007	-9999	-10000	0	0
mol:GDP	0.018	0.01	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
GADD45A	0.13	0.055	-9999	-0.48	1	1
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.083	0.011	-9999	-10000	0	0
MST1	0.02	0.071	-9999	-0.68	3	3
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.064	0.019	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.044	0.031	-9999	-10000	0	0
MAPK9	0.046	0.005	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.005	0.017	-9999	-10000	0	0
SOD2	0.16	0.054	-9999	-10000	0	0
RBL2	0.12	0.072	-9999	-10000	0	0
RAL/GDP	0.035	0.011	-9999	-10000	0	0
CHUK	0.027	0.009	-9999	-10000	0	0
Ran/GTP	0.015	0.001	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.045	0.008	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.016	0.26	-9999	-0.89	21	21
SKP2	0.013	0	-9999	-10000	0	0
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.027	0.009	-9999	-10000	0	0
CCNB1	0.12	0.094	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	0.006	0.03	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.007	-9999	-10000	0	0
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.025	0.038	-9999	-0.63	1	1
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.002	-9999	-10000	0	0
ZFAND5	0.11	0.044	-9999	-10000	0	0
SFN	0.011	0.038	-9999	-0.64	1	1
CDK2	0.014	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.078	0.031	-9999	-10000	0	0
CREBBP	0.014	0.002	-9999	-10000	0	0
FBXO32	0.11	0.14	-9999	-1.3	2	2
BCL6	0.12	0.072	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	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	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.028	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.046	-9999	-0.46	1	1
NFKBIA	0.023	0.052	-9999	-0.54	1	1
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.028	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.028	0	-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	0.013	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.047	-9999	-0.43	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.048	0.045	-9999	-0.45	1	1
SRC	0.013	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.047	-9999	-0.43	1	1
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.011	0.038	-9999	-0.64	1	1
I kappa B alpha/PIK3R1	0.029	0.049	-9999	-0.51	1	1
cell death	-0.006	0.034	-9999	-0.43	1	1
NF kappa B1 p105/c-Rel	0.028	0	-9999	-10000	0	0
LCK	-0.014	0.15	-9999	-0.8	10	10
BCL3	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.029	0.086	-9999	-0.48	3	3
KLHL20	-0.01	0.037	-9999	-0.29	1	1
CYFIP2	0.009	0.053	-9999	-0.64	2	2
Rac1/GDP	0.06	0.038	-9999	-10000	0	0
ENAH	0.04	0.053	-9999	-0.48	3	3
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.011	0.047	-9999	-0.8	1	1
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.011	0.038	-9999	-0.64	1	1
CDC42/GTP	-0.003	0.026	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.026	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.04	-9999	-10000	0	0
RAPGEF1	0.054	0.046	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.005	0.05	-9999	-0.5	3	3
CRK	0.048	0.05	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	-0.004	0.049	-9999	-0.58	2	2
alphaE/beta7 Integrin	-0.002	0.027	-9999	-0.47	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.002	0.028	-9999	-0.49	1	1
DLG1	0.04	0.053	-9999	-0.48	3	3
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.018	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.005	0.045	-9999	-0.39	4	4
PI3K	-0.003	0.023	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.004	0.056	-9999	-0.67	2	2
TIAM1	0.007	0.065	-9999	-0.64	3	3
E-cadherin(dimer)/Ca2+	-0.003	0.033	-9999	-10000	0	0
AKT1	-0.002	0.013	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.009	0.053	-9999	-0.64	2	2
RhoA/GDP	0.06	0.038	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.028	-9999	-0.2	1	1
CDC42/GDP	0.06	0.038	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.024	0.038	-9999	-0.56	1	1
ITGB7	0.011	0.038	-9999	-0.64	1	1
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.003	0.035	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.003	0.034	-9999	-10000	0	0
mol:GDP	0.057	0.043	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.038	-9999	-0.64	1	1
p120 catenin/RhoA/GDP	-0.003	0.028	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.03	0.047	-9999	-0.24	7	7
NME1	0.011	0.047	-9999	-0.8	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.04	0.053	-9999	-0.48	3	3
regulation of cell-cell adhesion	-0.003	0.023	-9999	-10000	0	0
WASF2	-0.004	0.013	-9999	-10000	0	0
Rap1/GTP	-0.003	0.03	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.004	0.046	-9999	-0.67	1	1
CCND1	0.034	0.058	-9999	-0.31	7	7
VAV2	0.041	0.075	-9999	-10000	0	0
RAP1/GDP	-0.001	0.032	-9999	-10000	0	0
adherens junction assembly	0.04	0.051	-9999	-0.46	3	3
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.005	0.047	-9999	-0.64	1	1
E-cadherin/beta catenin	-0.003	0.034	-9999	-0.41	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.04	0.053	-9999	-0.48	3	3
PIK3CA	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.016	0.06	-9999	-0.43	2	2
E-cadherin/beta catenin/alpha catenin	-0.004	0.039	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.051	-9999	-0.51	3	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.013	-9999	-9999
NPC/RanGAP1/SUMO1	0.019	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.013	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.013	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.013	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.013	-9999	-9999
UBE2I	0.013	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.013	-9999	-9999
PIAS1	0.013	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-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	0.035	-9999	-0.61	1	1
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-10000	0	0
CD4	0.009	0.06	-9999	-0.72	2	2
CLTA	0.013	0	-9999	-10000	0	0
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	0.03	0	-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	0.011	0.047	-9999	-0.8	1	1
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	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	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.028	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	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	0.024	-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	-0.005	0.048	-9999	-0.48	3	3

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.003	0.036	-9999	-0.45	2	2
NFKB1	0.013	0	-9999	-10000	0	0
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.004	0.05	-9999	-0.61	2	2
RELB	0.008	0.066	-9999	-0.8	2	2
NFKB2	0.013	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.004	0.043	-9999	-0.54	2	2
regulation of B cell activation	-0.004	0.043	-9999	-0.53	2	2

pid_entity	TCGA.IQ.7632	TCGA.IQ.7631	TCGA.IQ.7630	TCGA.HD.7917
109_MAP3K5	0.06	0.06	0.06	0.06
47_PPARGC1A	0.013	0.013	0.013	0.013
105_BMP4	0.013	0.013	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	0.013	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	-0.35	-0.35	-0.35	-0.35
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.019	0.019
84_STAT5B	-0.071	-0.22	-0.031	0.049
84_STAT5A	-0.071	-0.22	-0.031	0.049