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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	187
Syndecan-1-mediated signaling events	168
Syndecan-4-mediated signaling events	121
IL4-mediated signaling events	120
HIF-1-alpha transcription factor network	94
Osteopontin-mediated events	80
IL23-mediated signaling events	69
amb2 Integrin signaling	65
Glypican 2 network	63
Syndecan-2-mediated signaling events	57

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	0.4410	187	1499	8	-0.35	0.15	1000	-1000	-0.026	-1000
Syndecan-1-mediated signaling events	0.3962	168	5745	34	-0.72	0.014	1000	-1000	-0.068	-1000
Syndecan-4-mediated signaling events	0.2854	121	8139	67	-0.71	0.095	1000	-1000	-0.11	-1000
IL4-mediated signaling events	0.2830	120	10994	91	-1.4	1.3	1000	-1000	-0.19	-1000
HIF-1-alpha transcription factor network	0.2217	94	7213	76	-1	0.022	1000	-1000	-0.2	-1000
Osteopontin-mediated events	0.1887	80	3061	38	-0.43	0.014	1000	-1000	-0.14	-1000
IL23-mediated signaling events	0.1627	69	4147	60	-0.74	0.014	1000	-1000	-0.19	-1000
amb2 Integrin signaling	0.1533	65	5397	82	-0.59	0.014	1000	-1000	-0.099	-1000
Glypican 2 network	0.1486	63	253	4	-0.13	-0.13	1000	-1000	-0.038	-1000
Syndecan-2-mediated signaling events	0.1344	57	3940	69	-0.44	0.024	1000	-1000	-0.067	-1000
TCGA08_p53	0.1344	57	400	7	-0.27	0.14	1000	-1000	-0.02	-1000
Endothelins	0.1250	53	5105	96	-0.56	0.014	1000	-1000	-0.1	-1000
p75(NTR)-mediated signaling	0.0873	37	4704	125	-0.56	0.014	1000	-1000	-0.13	-1000
FOXA2 and FOXA3 transcription factor networks	0.0825	35	1628	46	-0.51	0.021	1000	-1000	-0.12	-1000
Visual signal transduction: Rods	0.0825	35	1847	52	-0.45	0.014	1000	-1000	-0.1	-1000
Calcium signaling in the CD4+ TCR pathway	0.0802	34	1069	31	-0.5	0.014	1000	-1000	-0.1	-1000
Signaling events mediated by the Hedgehog family	0.0731	31	1635	52	-0.47	0.067	1000	-1000	-0.097	-1000
BMP receptor signaling	0.0731	31	2526	81	-0.37	0.047	1000	-1000	-0.12	-1000
Effects of Botulinum toxin	0.0731	31	825	26	-0.23	0.014	1000	-1000	-0.083	-1000
PDGFR-beta signaling pathway	0.0731	31	3085	97	-0.16	0.014	1000	-1000	-0.11	-1000
Ephrin B reverse signaling	0.0708	30	1446	48	-0.15	0.14	1000	-1000	-0.094	-1000
Coregulation of Androgen receptor activity	0.0684	29	2223	76	-0.53	0.041	1000	-1000	-0.059	-1000
Glypican 1 network	0.0684	29	1415	48	-0.37	0.033	1000	-1000	-0.069	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0684	29	2006	68	-0.54	0.034	1000	-1000	-0.16	-1000
Signaling events regulated by Ret tyrosine kinase	0.0637	27	2242	82	-0.18	0.014	1000	-1000	-0.1	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0637	27	2126	78	-0.14	0.038	1000	-1000	-0.096	-1000
IL12-mediated signaling events	0.0613	26	2281	87	-0.27	0.082	1000	-1000	-0.16	-1000
Visual signal transduction: Cones	0.0613	26	1022	38	-0.2	0.014	1000	-1000	-0.086	-1000
Glucocorticoid receptor regulatory network	0.0613	26	3077	114	-0.65	0.26	1000	-1000	-0.093	-1000
LPA4-mediated signaling events	0.0566	24	296	12	-0.11	0.021	1000	-1000	-0.037	-1000
Caspase cascade in apoptosis	0.0566	24	1799	74	-0.14	0.049	1000	-1000	-0.066	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0566	24	2983	120	-0.27	0.12	1000	-1000	-0.1	-1000
ErbB4 signaling events	0.0542	23	1643	69	-0.34	0.066	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0542	23	2180	93	-0.29	0.16	1000	-1000	-0.099	-1000
Canonical Wnt signaling pathway	0.0542	23	1200	51	-0.35	0.11	1000	-1000	-0.084	-1000
Nongenotropic Androgen signaling	0.0542	23	1229	52	-0.14	0.043	1000	-1000	-0.075	-1000
Reelin signaling pathway	0.0519	22	1248	56	-0.23	0.014	1000	-1000	-0.086	-1000
IL1-mediated signaling events	0.0519	22	1367	62	-0.24	0.071	1000	-1000	-0.13	-1000
Thromboxane A2 receptor signaling	0.0495	21	2209	105	-0.098	0.022	1000	-1000	-0.085	-1000
EPHB forward signaling	0.0495	21	1827	85	-0.26	0.11	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0495	21	2148	99	-0.15	0.035	1000	-1000	-0.11	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0472	20	692	34	-0.056	0.014	1000	-1000	-0.079	-1000
Integrins in angiogenesis	0.0472	20	1724	84	-0.4	0.014	1000	-1000	-0.12	-1000
Regulation of nuclear SMAD2/3 signaling	0.0448	19	2595	136	-0.37	0.37	1000	-1000	-0.092	-1000
Signaling mediated by p38-gamma and p38-delta	0.0448	19	290	15	-0.14	0.024	1000	-1000	-0.048	-1000
Syndecan-3-mediated signaling events	0.0448	19	674	35	-0.22	0.014	1000	-1000	-0.088	-1000
IL27-mediated signaling events	0.0448	19	982	51	-0.17	0.05	1000	-1000	-0.11	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0448	19	643	33	-0.35	0.037	1000	-1000	-0.08	-1000
LPA receptor mediated events	0.0425	18	1873	102	-0.59	0.022	1000	-1000	-0.12	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0425	18	1620	88	-0.39	0.063	1000	-1000	-0.13	-1000
ErbB2/ErbB3 signaling events	0.0401	17	1123	65	-0.34	0.026	1000	-1000	-0.076	-1000
Presenilin action in Notch and Wnt signaling	0.0401	17	1074	61	-0.35	0.04	1000	-1000	-0.084	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0377	16	898	54	-0.32	0.028	1000	-1000	-0.12	-1000
Wnt signaling	0.0377	16	112	7	-0.076	0.014	1000	-1000	-0.045	-1000
Regulation of Androgen receptor activity	0.0377	16	1132	70	-0.55	0.033	1000	-1000	-0.089	-1000
Signaling events mediated by PTP1B	0.0354	15	1214	76	-0.18	0.033	1000	-1000	-0.1	-1000
Ephrin A reverse signaling	0.0330	14	101	7	-0.023	0	1000	-1000	-0.041	-1000
Arf6 signaling events	0.0330	14	899	62	-0.17	0.042	1000	-1000	-0.078	-1000
EPO signaling pathway	0.0307	13	732	55	-0.071	0.03	1000	-1000	-0.12	-1000
PDGFR-alpha signaling pathway	0.0307	13	609	44	-0.14	0.032	1000	-1000	-0.071	-1000
Signaling events mediated by HDAC Class III	0.0307	13	522	40	-0.19	0.076	1000	-1000	-0.056	-1000
TRAIL signaling pathway	0.0307	13	657	48	-0.088	0.016	1000	-1000	-0.089	-1000
Signaling mediated by p38-alpha and p38-beta	0.0307	13	586	44	-0.18	0.014	1000	-1000	-0.064	-1000
Regulation of Telomerase	0.0307	13	1372	102	-0.18	0.046	1000	-1000	-0.13	-1000
EGFR-dependent Endothelin signaling events	0.0307	13	284	21	-0.1	0.014	1000	-1000	-0.092	-1000
Plasma membrane estrogen receptor signaling	0.0283	12	1048	86	-0.3	0.03	1000	-1000	-0.1	-1000
Cellular roles of Anthrax toxin	0.0259	11	443	39	-0.042	0.018	1000	-1000	-0.041	-1000
Nectin adhesion pathway	0.0259	11	696	63	-0.16	0.041	1000	-1000	-0.085	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0259	11	423	37	-0.077	0.014	1000	-1000	-0.069	-1000
S1P1 pathway	0.0259	11	414	36	-0.16	0.014	1000	-1000	-0.076	-1000
Retinoic acid receptors-mediated signaling	0.0259	11	661	58	-0.17	0.027	1000	-1000	-0.096	-1000
Signaling events mediated by PRL	0.0236	10	371	34	-0.12	0.037	1000	-1000	-0.052	-1000
Class IB PI3K non-lipid kinase events	0.0236	10	30	3	-0.004	-1000	1000	-1000	-0.023	-1000
Noncanonical Wnt signaling pathway	0.0212	9	241	26	-0.076	0.014	1000	-1000	-0.11	-1000
Fc-epsilon receptor I signaling in mast cells	0.0212	9	955	97	-0.2	0.035	1000	-1000	-0.11	-1000
IFN-gamma pathway	0.0212	9	630	68	-0.18	0.037	1000	-1000	-0.12	-1000
FAS signaling pathway (CD95)	0.0212	9	457	47	-0.093	0.014	1000	-1000	-0.059	-1000
IL6-mediated signaling events	0.0212	9	730	75	-0.1	0.064	1000	-1000	-0.12	-1000
JNK signaling in the CD4+ TCR pathway	0.0189	8	139	17	-0.035	0.038	1000	-1000	-0.083	-1000
Arf6 downstream pathway	0.0189	8	364	43	-0.035	0.022	1000	-1000	-0.044	-1000
IL2 signaling events mediated by PI3K	0.0189	8	473	58	-0.14	0.061	1000	-1000	-0.11	-1000
S1P3 pathway	0.0189	8	375	42	-0.16	0.038	1000	-1000	-0.076	-1000
Rapid glucocorticoid signaling	0.0189	8	160	20	-0.059	0.014	1000	-1000	-0.05	-1000
FOXM1 transcription factor network	0.0189	8	425	51	-0.35	0.15	1000	-1000	-0.22	-1000
Ras signaling in the CD4+ TCR pathway	0.0189	8	151	17	-0.017	0.027	1000	-1000	-0.049	-1000
Circadian rhythm pathway	0.0165	7	160	22	-0.14	0.046	1000	-1000	-0.071	-1000
a4b1 and a4b7 Integrin signaling	0.0165	7	39	5	-0.018	0.011	1000	-1000	-0.046	-1000
Ceramide signaling pathway	0.0165	7	556	76	-0.098	0.036	1000	-1000	-0.08	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0165	7	411	52	-0.23	0.037	1000	-1000	-0.076	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0165	7	321	45	-0.088	0.041	1000	-1000	-0.12	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0165	7	575	74	-0.33	0.083	1000	-1000	-0.11	-1000
IGF1 pathway	0.0165	7	424	57	-0.079	0.025	1000	-1000	-0.11	-1000
Aurora B signaling	0.0165	7	494	67	-0.31	0.032	1000	-1000	-0.082	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0142	6	178	28	-0.083	0.017	1000	-1000	-0.067	-1000
Paxillin-dependent events mediated by a4b1	0.0142	6	239	36	-0.063	0.025	1000	-1000	-0.08	-1000
Insulin Pathway	0.0142	6	468	74	-0.25	0.039	1000	-1000	-0.12	-1000
VEGFR1 specific signals	0.0142	6	368	56	-0.14	0.04	1000	-1000	-0.099	-1000
p38 MAPK signaling pathway	0.0142	6	284	44	-0.14	0.02	1000	-1000	-0.085	-1000
BARD1 signaling events	0.0118	5	291	57	-0.024	0.058	1000	-1000	-0.084	-1000
Aurora A signaling	0.0118	5	308	60	-0.077	0.032	1000	-1000	-0.072	-1000
HIF-2-alpha transcription factor network	0.0118	5	247	43	-0.25	0.025	1000	-1000	-0.11	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0118	5	642	125	-0.098	0.094	1000	-1000	-0.12	-1000
IL2 signaling events mediated by STAT5	0.0118	5	120	22	-0.041	0.052	1000	-1000	-0.072	-1000
S1P4 pathway	0.0118	5	127	25	-0.028	0.025	1000	-1000	-0.071	-1000
Regulation of p38-alpha and p38-beta	0.0094	4	241	54	-0.11	0.036	1000	-1000	-0.079	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0071	3	332	85	-0.074	0.059	1000	-1000	-0.091	-1000
Hedgehog signaling events mediated by Gli proteins	0.0071	3	244	65	-0.094	0.066	1000	-1000	-0.091	-1000
ceramide signaling pathway	0.0071	3	149	49	-0.027	0.047	1000	-1000	-0.065	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0071	3	275	83	-0.076	0.066	1000	-1000	-0.089	-1000
TCGA08_rtk_signaling	0.0071	3	80	26	-0.031	0.048	1000	-1000	-0.027	-1000
Class I PI3K signaling events	0.0071	3	267	73	-0.11	0.04	1000	-1000	-0.08	-1000
Arf6 trafficking events	0.0071	3	256	71	-0.25	0.047	1000	-1000	-0.092	-1000
Signaling events mediated by HDAC Class II	0.0047	2	156	75	-0.049	0.032	1000	-1000	-0.077	-1000
Aurora C signaling	0.0047	2	18	7	-0.011	0.005	1000	-1000	-0.049	-1000
PLK1 signaling events	0.0047	2	253	85	-0.023	0.035	1000	-1000	-0.062	-1000
S1P5 pathway	0.0047	2	39	17	-0.015	0.025	1000	-1000	-0.065	-1000
E-cadherin signaling in keratinocytes	0.0047	2	96	43	-0.018	0.047	1000	-1000	-0.083	-1000
E-cadherin signaling events	0.0047	2	13	5	-0.006	0.012	1000	-1000	-0.052	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0024	1	31	23	-0.015	0.05	1000	-1000	-0.093	-1000
Canonical NF-kappaB pathway	0.0024	1	68	39	-0.029	0.088	1000	-1000	-0.12	-1000
Insulin-mediated glucose transport	0.0024	1	34	32	-0.077	0.048	1000	-1000	-0.084	-1000
Signaling events mediated by HDAC Class I	0.0024	1	146	104	-0.13	0.061	1000	-1000	-0.083	-1000
FoxO family signaling	0.0024	1	88	64	-0.024	0.16	1000	-1000	-0.097	-1000
Atypical NF-kappaB pathway	0.0024	1	34	31	-0.006	0.049	1000	-1000	-0.061	-1000
E-cadherin signaling in the nascent adherens junction	0.0024	1	129	76	-0.016	0.06	1000	-1000	-0.1	-1000
Alternative NF-kappaB pathway	0.0024	1	15	13	-0.004	0.014	1000	-1000	-0.081	-1000
PLK2 and PLK4 events	0.0000	0	2	3	0.012	0.024	1000	-1000	-0.026	-1000
mTOR signaling pathway	0.0000	0	37	53	-0.003	0.034	1000	-1000	-0.073	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	13	68	-0.12	0.063	1000	-1000	-0.075	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.075	-1000
Arf1 pathway	0.0000	0	10	54	-0.005	0.036	1000	-1000	-0.048	-1000
Total	NA	2655	152051	7203	-28	-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	0.23	-10000	0	-0.56	85	85
CDKN2C	0.017	0.14	-10000	0	-0.75	12	12
CDKN2A	-0.35	0.4	-10000	0	-0.78	194	194
CCND2	0.13	0.13	0.23	241	-0.15	1	242
RB1	-0.14	0.14	-10000	0	-0.24	240	240
CDK4	0.15	0.15	0.26	245	-10000	0	245
CDK6	0.14	0.15	0.25	240	-10000	0	240
G1/S progression	0.13	0.15	0.24	241	-10000	0	241

×

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	0.012	0.04	-9999	-0.82	1	1
CCL5	-0.1	0.29	-9999	-0.81	60	60
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.45	0.18	-9999	-0.55	301	301
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	-0.52	301	301
Syndecan-1/Syntenin	-0.42	0.17	-9999	-0.52	301	301
MAPK3	-0.37	0.16	-9999	-0.46	301	301
HGF/MET	-0.024	0.11	-9999	-0.51	20	20
TGFB1/TGF beta receptor Type II	0.012	0.04	-9999	-0.82	1	1
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.42	0.17	-9999	-0.51	301	301
Syndecan-1/RANTES	-0.49	0.24	-9999	-0.59	316	316
Syndecan-1/CD147	-0.4	0.17	-9999	-0.49	301	301
Syndecan-1/Syntenin/PIP2	-0.41	0.16	-9999	-0.5	301	301
LAMA5	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.4	0.16	-9999	-0.49	301	301
MMP7	-0.13	0.3	-9999	-0.76	79	79
HGF	-0.012	0.13	-9999	-0.66	16	16
Syndecan-1/CASK	-0.43	0.17	-9999	-0.52	301	301
Syndecan-1/HGF/MET	-0.42	0.18	-9999	-0.51	308	308
regulation of cell adhesion	-0.36	0.15	-9999	-0.59	56	56
HPSE	0.008	0.058	-9999	-0.59	4	4
positive regulation of cell migration	-0.45	0.18	-9999	-0.55	301	301
SDC1	-0.45	0.18	-9999	-0.55	301	301
Syndecan-1/Collagen	-0.45	0.18	-9999	-0.55	301	301
PPIB	0.014	0	-9999	-10000	0	0
MET	0.006	0.075	-9999	-0.76	4	4
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.59	0.37	-9999	-0.82	309	309
MAPK1	-0.37	0.16	-9999	-0.46	283	283
homophilic cell adhesion	-0.44	0.17	-9999	-0.54	301	301
MMP1	-0.72	0.27	-9999	-0.82	375	375

×

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	-0.24	0.23	-9999	-0.47	207	207
Syndecan-4/Syndesmos	-0.4	0.26	-9999	-0.63	206	206
positive regulation of JNK cascade	-0.41	0.22	-9999	-0.58	231	231
Syndecan-4/ADAM12	-0.71	0.36	-9999	-0.94	282	282
CCL5	-0.1	0.29	-9999	-0.81	60	60
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.26	0.39	-9999	-0.82	137	137
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0	0.079	-9999	-0.8	4	4
ADAM12	-0.6	0.36	-9999	-0.82	316	316
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.12	0.063	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.57	0.33	-9999	-0.79	256	256
Syndecan-4/CXCL12/CXCR4	-0.43	0.26	-9999	-0.62	231	231
Syndecan-4/Laminin alpha3	-0.52	0.34	-9999	-0.77	239	239
MDK	-0.009	0.14	-9999	-0.8	12	12
Syndecan-4/FZD7	-0.41	0.26	-9999	-0.63	208	208
Syndecan-4/Midkine	-0.41	0.26	-9999	-0.64	212	212
FZD7	-0.003	0.12	-9999	-0.79	9	9
Syndecan-4/FGFR1/FGF	-0.39	0.23	-9999	-0.59	213	213
THBS1	-0.014	0.14	-9999	-0.76	15	15
integrin-mediated signaling pathway	-0.46	0.31	-9999	-0.7	223	223
positive regulation of MAPKKK cascade	-0.41	0.22	-9999	-0.58	231	231
Syndecan-4/TACI	-0.45	0.29	-9999	-0.67	227	227
CXCR4	-0.014	0.15	-9999	-0.82	14	14
cell adhesion	-0.2	0.22	-9999	-0.4	202	202
Syndecan-4/Dynamin	-0.4	0.26	-9999	-0.63	206	206
Syndecan-4/TSP1	-0.42	0.28	-9999	-0.65	207	207
Syndecan-4/GIPC	-0.4	0.26	-9999	-0.63	206	206
Syndecan-4/RANTES	-0.46	0.3	-9999	-0.69	230	230
ITGB1	0.012	0.04	-9999	-0.82	1	1
LAMA1	-0.31	0.4	-9999	-0.81	167	167
LAMA3	-0.22	0.38	-9999	-0.82	122	122
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.095	0.068	-9999	-0.78	1	1
Syndecan-4/alpha-Actinin	-0.4	0.26	-9999	-0.63	206	206
TFPI	0.008	0.064	-9999	-0.74	3	3
F2	-0.083	0.25	-9999	-0.82	42	42
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.63	138	138
positive regulation of cell adhesion	-0.64	0.37	-9999	-0.86	277	277
ACTN1	0.012	0.04	-9999	-0.82	1	1
TNC	-0.15	0.33	-9999	-0.82	82	82
Syndecan-4/CXCL12	-0.43	0.26	-9999	-0.64	226	226
FGF6	0.003	0.005	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	-0.051	0.19	-9999	-0.6	45	45
TNFRSF13B	-0.076	0.25	-9999	-0.81	45	45
FGF2	-0.01	0.12	-9999	-0.65	15	15
FGFR1	0.004	0.09	-9999	-0.82	5	5
Syndecan-4/PI-4-5-P2	-0.41	0.26	-9999	-0.63	206	206
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.38	0.42	-9999	-0.81	207	207
cell migration	-0.04	0.02	-9999	-10000	0	0
PRKCD	0.027	0.011	-9999	-10000	0	0
vasculogenesis	-0.4	0.26	-9999	-0.62	207	207
SDC4	-0.43	0.28	-9999	-0.67	206	206
Syndecan-4/Tenascin C	-0.48	0.33	-9999	-0.74	223	223
Syndecan-4/PI-4-5-P2/PKC alpha	-0.094	0.049	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.4	0.26	-9999	-0.63	206	206
MMP9	-0.59	0.37	-9999	-0.81	309	309
Rac1/GTP	-0.21	0.22	-9999	-0.41	202	202
cytoskeleton organization	-0.38	0.25	-9999	-0.6	206	206
GIPC1	0.014	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.4	0.26	-9999	-0.63	207	207

×

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	0.49	-10000	0	-1.4	262	262
STAT6 (cleaved dimer)	-1.1	0.52	-10000	0	-1.4	312	312
IGHG1	-0.33	0.12	-10000	0	-0.46	91	91
IGHG3	-1	0.47	-10000	0	-1.3	301	301
AKT1	-0.4	0.18	-10000	0	-0.72	35	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.29	0.15	-10000	0	-0.71	21	21
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.42	0.17	-10000	0	-0.71	31	31
THY1	-1.1	0.55	-10000	0	-1.5	286	286
MYB	-0.054	0.19	-10000	0	-0.6	46	46
HMGA1	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.52	0.22	-10000	0	-0.7	146	146
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.42	0.17	-10000	0	-0.7	32	32
SP1	0.012	0.012	-10000	0	-10000	0	0
INPP5D	0.011	0.041	-10000	0	-0.59	2	2
SOCS5	0.036	0.01	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-1.1	0.51	-10000	0	-1.4	291	291
SOCS1	-0.65	0.26	-10000	0	-0.83	231	231
SOCS3	-0.43	0.19	-10000	0	-0.82	27	27
FCER2	-0.76	0.35	-10000	0	-1	189	189
PARP14	0.008	0.07	-10000	0	-0.82	3	3
CCL17	-1.1	0.51	-10000	0	-1.4	273	273
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.33	0.15	-10000	0	-0.72	18	18
T cell proliferation	-1.1	0.53	-10000	0	-1.4	286	286
IL4R/JAK1	-1.1	0.5	-10000	0	-1.4	282	282
EGR2	-1.1	0.5	-10000	0	-1.4	277	277
JAK2	-0.032	0.034	-10000	0	-0.63	1	1
JAK3	0	0.13	-10000	0	-0.82	11	11
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
JAK1	0.001	0.005	-10000	0	-10000	0	0
COL1A2	-0.53	0.36	-10000	0	-0.94	183	183
CCL26	-1.1	0.5	-10000	0	-1.4	270	270
IL4R	-1.2	0.54	-10000	0	-1.5	281	281
PTPN6	0.035	0.007	-10000	0	-10000	0	0
IL13RA2	-1.1	0.52	-10000	0	-1.5	267	267
IL13RA1	-0.031	0.018	-10000	0	-10000	0	0
IRF4	-0.28	0.33	-10000	0	-0.92	75	75
ARG1	-0.52	0.55	-10000	0	-1.3	120	120
CBL	-0.48	0.21	-10000	0	-0.85	43	43
GTF3A	0.006	0.018	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.044	0.03	-10000	0	-0.47	1	1
IRF4/BCL6	-0.25	0.3	-10000	0	-0.86	74	74
CD40LG	-0.059	0.21	-10000	0	-0.61	53	53
MAPK14	-0.48	0.21	-10000	0	-0.87	40	40
mitosis	-0.39	0.17	-10000	0	-0.68	35	35
STAT6	-1.3	0.69	-10000	0	-1.7	293	293
SPI1	-0.014	0.068	-10000	0	-0.73	2	2
RPS6KB1	-0.37	0.16	-10000	0	-0.68	25	25
STAT6 (dimer)	-1.3	0.7	-10000	0	-1.7	293	293
STAT6 (dimer)/PARP14	-1.2	0.59	-10000	0	-1.5	289	289
mast cell activation	0.021	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.4	0.18	-10000	0	-0.73	36	36
FRAP1	-0.4	0.18	-10000	0	-0.72	35	35
LTA	-1.1	0.5	-10000	0	-1.4	287	287
FES	0.014	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	1.3	0.62	1.6	295	-10000	0	295
CCL11	-1.2	0.48	-10000	0	-1.4	309	309
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.39	0.18	-10000	0	-0.72	35	35
IL2RG	-0.006	0.15	-10000	0	-0.8	14	14
IL10	-1.1	0.5	-10000	0	-1.4	282	282
IRS1	0.011	0.041	-10000	0	-0.59	2	2
IRS2	0.011	0.041	-10000	0	-0.59	2	2
IL4	-0.21	0.069	-10000	0	-10000	0	0
IL5	-1.1	0.49	-10000	0	-1.4	282	282
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.78	0.3	-10000	0	-0.98	267	267
COL1A1	-0.7	0.36	-10000	0	-0.96	271	271
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-1.1	0.53	-10000	0	-1.5	268	268
IL2R gamma/JAK3	-0.013	0.16	-10000	0	-0.67	23	23
TFF3	-1.3	0.58	-10000	0	-1.6	315	315
ALOX15	-1.2	0.53	-10000	0	-1.5	287	287
MYBL1	-0.006	0.13	-10000	0	-0.82	10	10
T-helper 2 cell differentiation	-0.8	0.32	-10000	0	-0.99	286	286
SHC1	0.014	0	-10000	0	-10000	0	0
CEBPB	-0.01	0.046	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.4	0.17	-10000	0	-0.7	28	28
mol:PI-3-4-5-P3	-0.4	0.18	-10000	0	-0.72	35	35
PI3K	-0.42	0.19	-10000	0	-0.77	35	35
DOK2	0.007	0.07	-10000	0	-0.7	4	4
ETS1	0.029	0.071	-10000	0	-0.8	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.31	0.14	-10000	0	-0.69	18	18
ITGB3	-1.1	0.5	-10000	0	-1.4	282	282
PIGR	-1.4	0.6	-10000	0	-1.7	323	323
IGHE	0.054	0.046	0.27	4	-10000	0	4
MAPKKK cascade	-0.31	0.14	-10000	0	-0.68	18	18
BCL6	0.013	0.002	-10000	0	-10000	0	0
OPRM1	-1.1	0.49	-10000	0	-1.4	278	278
RETNLB	-1.1	0.5	-10000	0	-1.4	280	280
SELP	-1.2	0.54	-10000	0	-1.5	290	290
AICDA	-1.1	0.48	-10000	0	-1.3	289	289

×

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	-0.7	0.48	-9999	-1.2	131	131
HDAC7	0.014	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.48	0.32	-9999	-0.88	74	74
SMAD4	0.014	0.029	-9999	-0.59	1	1
ID2	-0.7	0.48	-9999	-1.2	139	139
AP1	-0.056	0.14	-9999	-0.42	57	57
ABCG2	-0.7	0.48	-9999	-1.2	147	147
HIF1A	-0.083	0.054	-9999	-10000	0	0
TFF3	-0.83	0.54	-9999	-1.3	199	199
GATA2	0.006	0.085	-9999	-0.77	5	5
AKT1	-0.086	0.063	-9999	-10000	0	0
response to hypoxia	-0.11	0.065	-9999	-10000	0	0
MCL1	-0.7	0.48	-9999	-1.2	146	146
NDRG1	-0.7	0.48	-9999	-1.2	138	138
SERPINE1	-0.93	0.55	-9999	-1.4	220	220
FECH	-0.7	0.48	-9999	-1.2	146	146
FURIN	-0.7	0.48	-9999	-1.2	129	129
NCOA2	-0.024	0.15	-9999	-0.59	26	26
EP300	-0.091	0.095	-9999	-0.44	4	4
HMOX1	-0.7	0.48	-9999	-1.2	146	146
BHLHE40	-0.7	0.48	-9999	-1.2	136	136
BHLHE41	-0.71	0.49	-9999	-1.2	140	140
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.068	0.057	-9999	-10000	0	0
ENG	-0.044	0.072	-9999	-10000	0	0
JUN	0.014	0.001	-9999	-10000	0	0
RORA	-0.7	0.49	-9999	-1.2	146	146
ABCB1	-0.19	0.31	-9999	-1.4	24	24
TFRC	-0.72	0.48	-9999	-1.2	148	148
CXCR4	-0.71	0.49	-9999	-1.2	141	141
TF	-0.88	0.54	-9999	-1.3	225	225
CITED2	-0.7	0.48	-9999	-1.2	146	146
HIF1A/ARNT	-0.81	0.6	-9999	-1.4	187	187
LDHA	-0.069	0.045	-9999	-10000	0	0
ETS1	-0.7	0.48	-9999	-1.2	138	138
PGK1	-0.7	0.48	-9999	-1.2	140	140
NOS2	-0.76	0.5	-9999	-1.3	166	166
ITGB2	-0.71	0.48	-9999	-1.2	142	142
ALDOA	-0.7	0.48	-9999	-1.2	146	146
Cbp/p300/CITED2	-0.68	0.49	-9999	-1.3	116	116
FOS	-0.067	0.21	-9999	-0.59	57	57
HK2	-0.7	0.48	-9999	-1.2	146	146
SP1	0.022	0.005	-9999	-10000	0	0
GCK	-0.18	0.22	-9999	-0.82	31	31
HK1	-0.7	0.48	-9999	-1.2	146	146
NPM1	-0.7	0.48	-9999	-1.2	138	138
EGLN1	-0.7	0.48	-9999	-1.2	146	146
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.7	0.48	-9999	-1.2	146	146
SMAD3	0.014	0.029	-9999	-0.59	1	1
EDN1	-0.091	0.16	-9999	-1.4	3	3
IGFBP1	-0.72	0.49	-9999	-1.3	143	143
VEGFA	-0.4	0.29	-9999	-0.98	16	16
HIF1A/JAB1	-0.042	0.028	-9999	-10000	0	0
CP	-0.82	0.54	-9999	-1.3	184	184
CXCL12	-0.73	0.5	-9999	-1.3	143	143
COPS5	0.013	0.005	-9999	-10000	0	0
SMAD3/SMAD4	-0.002	0.029	-9999	-0.42	2	2
BNIP3	-0.7	0.48	-9999	-1.2	138	138
EGLN3	-0.72	0.5	-9999	-1.3	144	144
CA9	-1	0.5	-9999	-1.4	271	271
TERT	-0.77	0.52	-9999	-1.3	172	172
ENO1	-0.7	0.48	-9999	-1.2	138	138
PFKL	-0.7	0.48	-9999	-1.2	146	146
NCOA1	0.013	0.002	-9999	-10000	0	0
ADM	-0.7	0.48	-9999	-1.2	147	147
ARNT	-0.083	0.053	-9999	-10000	0	0
HNF4A	-0.068	0.24	-9999	-0.82	40	40
ADFP	-0.71	0.48	-9999	-1.2	183	183
SLC2A1	-0.41	0.3	-9999	-1	19	19
LEP	-0.75	0.52	-9999	-1.3	161	161
HIF1A/ARNT/Cbp/p300	-0.5	0.33	-9999	-0.88	94	94
EPO	-0.4	0.31	-9999	-0.99	51	51
CREBBP	-0.09	0.09	-9999	-0.37	2	2
HIF1A/ARNT/Cbp/p300/HDAC7	-0.47	0.33	-9999	-0.92	58	58
PFKFB3	-0.7	0.48	-9999	-1.2	146	146
NT5E	-0.77	0.53	-9999	-1.3	152	152

×

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	-0.26	0.28	-9999	-0.58	117	117
NF kappa B1 p50/RelA/I kappa B alpha	-0.27	0.24	-9999	-0.58	117	117
alphaV/beta3 Integrin/Osteopontin/Src	-0.33	0.32	-9999	-0.64	216	216
AP1	-0.34	0.3	-9999	-0.82	82	82
ILK	-0.27	0.29	-9999	-0.58	129	129
bone resorption	-0.21	0.25	-9999	-0.72	18	18
PTK2B	0.012	0.029	-9999	-0.59	1	1
PYK2/p130Cas	-0.25	0.25	-9999	-0.53	117	117
ITGAV	0.004	0.077	-9999	-0.77	4	4
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.008	0.058	-9999	-0.43	8	8
alphaV/beta3 Integrin/Osteopontin	-0.31	0.3	-9999	-0.59	222	222
MAP3K1	-0.27	0.29	-9999	-0.54	221	221
JUN	0.013	0.002	-9999	-10000	0	0
MAPK3	-0.28	0.29	-9999	-0.62	129	129
MAPK1	-0.28	0.29	-9999	-0.64	117	117
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.26	0.28	-9999	-0.57	132	132
ITGB3	-0.025	0.16	-9999	-0.75	20	20
NFKBIA	-0.28	0.29	-9999	-0.64	117	117
FOS	-0.069	0.21	-9999	-0.59	57	57
CD44	0.012	0.029	-9999	-0.59	1	1
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.43	0.4	-9999	-0.9	138	138
NF kappa B1 p50/RelA	-0.29	0.25	-9999	-0.62	117	117
BCAR1	0.014	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.034	0.14	-9999	-0.6	23	23
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.27	0.29	-9999	-0.53	221	221
VAV3	-0.27	0.29	-9999	-0.57	143	143
MAP3K14	-0.29	0.3	-9999	-0.55	221	221
ROCK2	0.004	0.077	-9999	-0.59	7	7
SPP1	-0.41	0.42	-9999	-0.82	214	214
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.26	0.25	-9999	-0.61	65	65
MMP2	-0.3	0.32	-9999	-0.81	87	87

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.57	0.44	-10000	0	-1.2	112	112
IL23A	-0.56	0.43	-10000	0	-1.2	90	90
NF kappa B1 p50/RelA/I kappa B alpha	-0.56	0.42	-10000	0	-1.1	112	112
positive regulation of T cell mediated cytotoxicity	-0.63	0.49	-10000	0	-1.2	127	127
ITGA3	-0.56	0.42	-10000	0	-1.1	104	104
IL17F	-0.38	0.27	-10000	0	-0.74	80	80
IL12B	-0.081	0.25	-10000	0	-0.86	39	39
STAT1 (dimer)	-0.62	0.48	-10000	0	-1.2	127	127
CD4	-0.55	0.41	-10000	0	-1.1	110	110
IL23	-0.57	0.43	-10000	0	-1.2	101	101
IL23R	-0.085	0.096	-10000	0	-0.7	6	6
IL1B	-0.59	0.45	-10000	0	-1.2	109	109
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.74	0.44	-10000	0	-1.1	182	182
TYK2	-0.005	0.043	-10000	0	-0.86	1	1
STAT4	-0.002	0.11	-10000	0	-0.79	8	8
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.007	0.12	-10000	0	-0.69	12	12
IL12RB1	-0.08	0.24	-10000	0	-0.84	39	39
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.069	0.19	-10000	0	-0.66	40	40
IL23R/JAK2	-0.1	0.1	-10000	0	-0.74	4	4
positive regulation of chronic inflammatory response	-0.63	0.49	-10000	0	-1.2	127	127
natural killer cell activation	0.008	0.008	0.06	6	-10000	0	6
JAK2	0.001	0.031	-10000	0	-0.59	1	1
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
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	-0.55	0.4	-10000	0	-1.1	102	102
ALOX12B	-0.65	0.48	-10000	0	-1.2	144	144
CXCL1	-0.58	0.45	-10000	0	-1.2	109	109
T cell proliferation	-0.63	0.49	-10000	0	-1.2	127	127
NFKBIA	0.01	0.003	-10000	0	-10000	0	0
IL17A	-0.29	0.22	-10000	0	-0.6	44	44
PI3K	-0.58	0.43	-10000	0	-1.1	125	125
IFNG	-0.032	0.046	0.13	5	-0.11	77	82
STAT3 (dimer)	-0.54	0.4	-10000	0	-1.1	112	112
IL18R1	0.007	0.065	-10000	0	-0.75	3	3
IL23/IL23R/JAK2/TYK2/SOCS3	-0.33	0.25	-10000	0	-0.79	44	44
IL18/IL18R	-0.004	0.12	-10000	0	-0.64	8	8
macrophage activation	-0.028	0.015	-10000	0	-0.045	67	67
TNF	-0.58	0.45	-10000	0	-1.2	101	101
STAT3/STAT4	-0.58	0.43	-10000	0	-1.1	124	124
STAT4 (dimer)	-0.6	0.47	-10000	0	-1.2	113	113
IL18	-0.009	0.11	-10000	0	-0.59	15	15
IL19	-0.69	0.53	-10000	0	-1.3	161	161
STAT5A (dimer)	-0.6	0.47	-10000	0	-1.2	120	120
STAT1	-0.039	0.2	-10000	0	-0.81	27	27
SOCS3	0.012	0.029	-10000	0	-0.59	1	1
CXCL9	-0.7	0.47	-10000	0	-1.2	173	173
MPO	-0.56	0.43	-10000	0	-1.2	98	98
positive regulation of humoral immune response	-0.63	0.49	-10000	0	-1.2	127	127
IL23/IL23R/JAK2/TYK2	-0.65	0.54	-10000	0	-1.3	120	120
IL6	-0.59	0.47	-10000	0	-1.2	108	108
STAT5A	0.014	0	-10000	0	-10000	0	0
IL2	0.006	0.041	-10000	0	-0.81	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.008	0.06	6	-10000	0	6
CD3E	-0.55	0.42	-10000	0	-1.1	98	98
keratinocyte proliferation	-0.63	0.49	-10000	0	-1.2	127	127
NOS2	-0.6	0.45	-10000	0	-1.2	120	120

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.15	0.29	-9999	-0.64	95	95
alphaM/beta2 Integrin/GPIbA	-0.078	0.22	-9999	-0.7	42	42
alphaM/beta2 Integrin/proMMP-9	-0.45	0.32	-9999	-0.61	311	311
PLAUR	-0.031	0.19	-9999	-0.82	23	23
HMGB1	0.01	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.062	0.2	-9999	-0.68	36	36
AGER	0.003	0.082	-9999	-0.82	4	4
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	0.014	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.078	0.2	-9999	-0.64	37	37
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.59	0.37	-9999	-0.82	309	309
CYR61	0.005	0.081	-9999	-0.73	5	5
TLN1	0.01	0.057	-9999	-0.82	2	2
Rap1/GTP	-0.17	0.16	-9999	-0.51	45	45
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.095	0.23	-9999	-0.59	76	76
MYH2	-0.38	0.25	-9999	-0.58	227	227
MST1R	0.002	0.082	-9999	-0.59	8	8
leukocyte activation during inflammatory response	-0.079	0.2	-9999	-0.56	57	57
APOB	-0.02	0.16	-9999	-0.8	16	16
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.12	0.31	-9999	-0.82	69	69
JAM3	0.012	0.04	-9999	-0.82	1	1
GP1BA	-0.016	0.15	-9999	-0.75	16	16
alphaM/beta2 Integrin/CTGF	-0.067	0.2	-9999	-0.66	39	39
alphaM/beta2 Integrin	-0.2	0.2	-9999	-0.44	140	140
JAM3 homodimer	0.012	0.04	-9999	-0.82	1	1
ICAM2	0.009	0.058	-9999	-0.67	3	3
ICAM1	-0.028	0.18	-9999	-0.82	21	21
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.2	0.2	-9999	-0.43	140	140
cell adhesion	-0.077	0.22	-9999	-0.69	42	42
NFKB1	-0.038	0.24	-9999	-0.84	19	19
THY1	-0.23	0.38	-9999	-0.82	123	123
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.033	0.13	-9999	-0.54	26	26
alphaM/beta2 Integrin/LRP/tPA	-0.068	0.2	-9999	-0.61	45	45
IL6	-0.069	0.3	-9999	-0.79	54	54
ITGB2	-0.017	0.15	-9999	-0.8	14	14
elevation of cytosolic calcium ion concentration	-0.29	0.33	-9999	-0.58	212	212
alphaM/beta2 Integrin/JAM2/JAM3	-0.062	0.19	-9999	-0.64	35	35
JAM2	0.001	0.087	-9999	-0.59	9	9
alphaM/beta2 Integrin/ICAM1	-0.082	0.22	-9999	-0.64	49	49
alphaM/beta2 Integrin/uPA/Plg	-0.28	0.3	-9999	-0.55	213	213
RhoA/GTP	-0.25	0.22	-9999	-0.52	132	132
positive regulation of phagocytosis	-0.16	0.18	-9999	-0.58	43	43
Ron/MSP	-0.014	0.083	-9999	-0.47	13	13
alphaM/beta2 Integrin/uPAR/uPA	-0.3	0.34	-9999	-0.59	212	212
alphaM/beta2 Integrin/uPAR	-0.088	0.25	-9999	-0.71	50	50
PLAU	-0.36	0.41	-9999	-0.82	188	188
PLAT	-0.01	0.14	-9999	-0.82	12	12
actin filament polymerization	-0.37	0.23	-9999	-0.55	227	227
MST1	0.005	0.081	-9999	-0.73	5	5
alphaM/beta2 Integrin/lipoprotein(a)	-0.08	0.21	-9999	-0.57	57	57
TNF	-0.042	0.26	-9999	-0.79	32	32
RAP1B	0.012	0.04	-9999	-0.82	1	1
alphaM/beta2 Integrin/uPA	-0.3	0.32	-9999	-0.6	209	209
fibrinolysis	-0.28	0.3	-9999	-0.55	213	213
HCK	0.007	0.07	-9999	-0.7	4	4
dendritic cell antigen processing and presentation	-0.2	0.2	-9999	-0.43	140	140
VTN	-0.045	0.21	-9999	-0.82	30	30
alphaM/beta2 Integrin/CYR61	-0.065	0.2	-9999	-0.68	38	38
LPA	-0.012	0.12	-9999	-0.82	10	10
LRP1	0.012	0.029	-9999	-0.59	1	1
cell migration	-0.48	0.37	-9999	-0.65	316	316
FN1	-0.39	0.42	-9999	-0.82	207	207
alphaM/beta2 Integrin/Thy1	-0.21	0.33	-9999	-0.64	138	138
MPO	-0.007	0.11	-9999	-0.64	13	13
KNG1	-0.022	0.15	-9999	-0.82	14	14
RAP1/GDP	-0.001	0.027	-9999	-0.55	1	1
ROCK1	-0.23	0.21	-9999	-0.5	124	124
ELA2	0	0	-9999	-10000	0	0
PLG	-0.006	0.079	-9999	-0.82	4	4
CTGF	0.002	0.087	-9999	-0.62	8	8
alphaM/beta2 Integrin/Hck	-0.064	0.2	-9999	-0.69	36	36
ITGAM	-0.05	0.21	-9999	-0.81	31	31
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.11	0.21	-9999	-0.66	34	34
HP	-0.24	0.3	-9999	-0.6	174	174
leukocyte adhesion	-0.18	0.26	-9999	-0.79	40	40
SELP	-0.095	0.23	-9999	-0.59	76	76

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.009	0.14	-9999	-0.8	12	12
GPC2	-0.13	0.32	-9999	-0.82	75	75
GPC2/Midkine	-0.13	0.26	-9999	-0.65	83	83
neuron projection morphogenesis	-0.13	0.26	-9999	-0.65	83	83

×

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	-0.27	0.32	-9999	-0.58	210	210
EPHB2	-0.15	0.33	-9999	-0.82	84	84
Syndecan-2/TACI	-0.062	0.2	-9999	-0.55	63	63
LAMA1	-0.31	0.4	-9999	-0.81	167	167
Syndecan-2/alpha2 ITGB1	-0.15	0.23	-9999	-0.47	138	138
HRAS	0.012	0.04	-9999	-0.82	1	1
Syndecan-2/CASK	-0.025	0.11	-9999	-0.55	19	19
ITGA5	-0.26	0.39	-9999	-0.82	137	137
BAX	0.015	0.12	-9999	-0.77	2	2
EPB41	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.022	0.1	-9999	-0.49	19	19
LAMA3	-0.22	0.38	-9999	-0.82	122	122
EZR	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.009	0.058	-9999	-0.67	3	3
Syndecan-2/MMP2	-0.09	0.26	-9999	-0.61	77	77
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.002	0.037	-9999	-0.53	2	2
dendrite morphogenesis	-0.11	0.25	-9999	-0.56	99	99
Syndecan-2/GM-CSF	-0.3	0.3	-9999	-0.56	237	237
determination of left/right symmetry	-0.007	0.13	-9999	-0.62	19	19
Syndecan-2/PKC delta	0.001	0.12	-9999	-0.54	19	19
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	-0.27	0.28	-9999	-0.51	237	237
MAPK1	-0.27	0.28	-9999	-0.51	237	237
Syndecan-2/RACK1	-0.022	0.098	-9999	-0.46	20	20
NF1	0.014	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.007	0.13	-9999	-0.62	19	19
ITGA2	0.012	0.029	-9999	-0.59	1	1
MAPK8	0.006	0.13	-9999	-0.52	24	24
Syndecan-2/alpha2/beta1 Integrin	-0.2	0.25	-9999	-0.49	171	171
Syndecan-2/Kininogen	-0.033	0.16	-9999	-0.57	31	31
ITGB1	0.012	0.04	-9999	-0.82	1	1
SRC	0.017	0.1	-9999	-0.44	20	20
Syndecan-2/CASK/Protein 4.1	-0.022	0.1	-9999	-0.5	19	19
extracellular matrix organization	0	0.12	-9999	-0.56	19	19
actin cytoskeleton reorganization	-0.27	0.31	-9999	-0.58	210	210
Syndecan-2/Caveolin-2/Ras	-0.026	0.11	-9999	-0.5	21	21
Syndecan-2/Laminin alpha3	-0.16	0.28	-9999	-0.56	137	137
Syndecan-2/RasGAP	-0.021	0.097	-9999	-0.46	20	20
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.63	138	138
PRKCD	0.014	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.11	0.25	-9999	-0.56	99	99
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.024	0.1	-9999	-0.43	20	20
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.076	0.25	-9999	-0.81	45	45
RASA1	0.012	0.029	-9999	-0.59	1	1
alpha2/beta1 Integrin	-0.002	0.037	-9999	-0.53	2	2
Syndecan-2/Synbindin	0.001	0.12	-9999	-0.54	19	19
TGFB1	0.012	0.04	-9999	-0.82	1	1
CASP3	0.012	0.11	-9999	-0.49	19	19
FN1	-0.39	0.42	-9999	-0.82	207	207
Syndecan-2/IL8	-0.12	0.26	-9999	-0.56	103	103
SDC2	-0.007	0.13	-9999	-0.63	19	19
KNG1	-0.022	0.15	-9999	-0.82	14	14
Syndecan-2/Neurofibromin	0.001	0.12	-9999	-0.54	19	19
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	-0.44	0.41	-9999	-0.82	229	229
Syndecan-2/TGFB1	0	0.12	-9999	-0.56	19	19
Syndecan-2/Syntenin/PI-4-5-P2	-0.022	0.1	-9999	-0.5	19	19
Syndecan-2/Ezrin	-0.022	0.1	-9999	-0.49	19	19
PRKACA	0.012	0.11	-9999	-0.49	19	19
angiogenesis	-0.12	0.26	-9999	-0.56	103	103
MMP2	-0.12	0.31	-9999	-0.82	69	69
IL8	-0.16	0.34	-9999	-0.81	89	89
calcineurin-NFAT signaling pathway	-0.062	0.2	-9999	-0.54	63	63

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.27	0.31	-10000	0	-0.6	194	194
TP53	-0.078	0.089	-10000	0	-0.43	4	4
Senescence	-0.078	0.088	-10000	0	-0.42	4	4
Apoptosis	-0.078	0.088	-10000	0	-0.42	4	4
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.14	0.15	0.3	194	-10000	0	194
MDM4	0.014	0	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.19	0.31	-10000	0	-0.7	59	59
PTK2B	0.012	0.029	-10000	0	-0.59	1	1
mol:Ca2+	-0.065	0.21	-10000	0	-0.68	26	26
EDN1	-0.11	0.21	-10000	0	-0.4	45	45
EDN3	-0.24	0.29	-10000	0	-0.59	176	176
EDN2	-0.092	0.25	-10000	0	-0.67	65	65
HRAS/GDP	-0.063	0.18	-10000	0	-0.55	13	13
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.065	0.16	-10000	0	-0.39	32	32
ADCY4	-0.2	0.25	-10000	0	-0.61	73	73
ADCY5	-0.29	0.26	-10000	0	-0.61	120	120
ADCY6	-0.21	0.26	-10000	0	-0.61	78	78
ADCY7	-0.2	0.25	-10000	0	-0.61	73	73
ADCY1	-0.23	0.28	-10000	0	-0.64	88	88
ADCY2	-0.31	0.26	-10000	0	-0.62	136	136
ADCY3	-0.2	0.25	-10000	0	-0.61	73	73
ADCY8	-0.22	0.26	-10000	0	-0.63	82	82
ADCY9	-0.21	0.25	-10000	0	-0.61	73	73
arachidonic acid secretion	-0.088	0.22	-10000	0	-0.53	51	51
ETB receptor/Endothelin-1/Gq/GTP	-0.064	0.14	-10000	0	-0.43	27	27
GNAO1	0.006	0.075	-10000	0	-0.76	4	4
HRAS	0.01	0.04	-10000	0	-0.82	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.12	0.36	0.34	112	-0.66	63	175
ETA receptor/Endothelin-1/Gs/GTP	-0.16	0.34	0.32	92	-0.62	85	177
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.45	0.5	-10000	0	-0.86	242	242
EDNRB	-0.018	0.062	-10000	0	-0.59	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.25	0.4	-10000	0	-0.98	67	67
CYSLTR1	-0.24	0.36	-10000	0	-0.78	79	79
SLC9A1	-0.074	0.16	-10000	0	-0.34	25	25
mol:GDP	-0.073	0.19	-10000	0	-0.47	33	33
SLC9A3	-0.2	0.33	-10000	0	-0.72	92	92
RAF1	-0.09	0.2	-10000	0	-0.51	40	40
JUN	-0.049	0.18	-10000	0	-0.59	9	9
JAK2	-0.2	0.31	-10000	0	-0.68	64	64
mol:IP3	-0.084	0.17	-10000	0	-0.47	33	33
ETA receptor/Endothelin-1	-0.16	0.43	0.4	114	-0.72	77	191
PLCB1	0.011	0.03	-10000	0	-0.59	1	1
PLCB2	0.009	0.05	-10000	0	-0.71	2	2
ETA receptor/Endothelin-3	-0.24	0.25	-10000	0	-0.5	178	178
FOS	-0.14	0.34	-10000	0	-0.94	59	59
Gai/GDP	0.012	0.079	-10000	0	-0.57	3	3
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.21	0.3	-10000	0	-0.69	69	69
BCAR1	0.014	0	-10000	0	-10000	0	0
PRKCB1	-0.082	0.16	-10000	0	-0.45	34	34
GNAQ	0.014	0.006	-10000	0	-10000	0	0
GNAZ	-0.015	0.15	-10000	0	-0.75	16	16
GNAL	-0.059	0.2	-10000	0	-0.59	51	51
Gs family/GDP	-0.13	0.15	-10000	0	-0.46	45	45
ETA receptor/Endothelin-1/Gq/GTP	-0.089	0.19	-10000	0	-0.45	43	43
MAPK14	-0.035	0.12	-10000	0	-0.6	5	5
TRPC6	-0.069	0.22	-10000	0	-0.72	25	25
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.029	-10000	0	-0.59	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.047	0.13	-10000	0	-0.38	24	24
ETB receptor/Endothelin-2	-0.083	0.19	-10000	0	-0.51	68	68
ETB receptor/Endothelin-3	-0.19	0.22	-10000	0	-0.44	178	178
ETB receptor/Endothelin-1	-0.088	0.18	-10000	0	-0.55	6	6
MAPK3	-0.12	0.3	-10000	0	-0.79	59	59
MAPK1	-0.12	0.3	-10000	0	-0.79	59	59
Rac1/GDP	-0.061	0.18	-10000	0	-0.55	12	12
cAMP biosynthetic process	-0.25	0.23	-10000	0	-0.58	95	95
MAPK8	-0.069	0.21	-10000	0	-0.61	23	23
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.02	0.098	-10000	0	-0.41	8	8
p130Cas/CRK/Src/PYK2	-0.067	0.19	-10000	0	-0.56	17	17
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.065	0.18	-10000	0	-0.56	15	15
COL1A2	-0.34	0.48	-10000	0	-0.86	184	184
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.13	0.23	-10000	0	-0.58	66	66
mol:DAG	-0.084	0.17	-10000	0	-0.47	33	33
MAP2K2	-0.1	0.24	-10000	0	-0.6	53	53
MAP2K1	-0.1	0.24	-10000	0	-0.61	50	50
EDNRA	-0.097	0.2	-10000	0	-0.97	3	3
positive regulation of muscle contraction	-0.16	0.28	-10000	0	-0.66	48	48
Gq family/GDP	-0.091	0.17	-10000	0	-0.5	33	33
HRAS/GTP	-0.087	0.18	-10000	0	-0.46	38	38
PRKCH	-0.073	0.16	-10000	0	-0.47	27	27
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.075	0.16	-10000	0	-0.47	28	28
PRKCB	-0.082	0.18	-10000	0	-0.49	35	35
PRKCE	-0.073	0.16	-10000	0	-0.46	28	28
PRKCD	-0.074	0.16	-10000	0	-0.47	28	28
PRKCG	-0.12	0.21	-10000	0	-0.52	63	63
regulation of vascular smooth muscle contraction	-0.16	0.4	-10000	0	-1.1	59	59
PRKCQ	-0.079	0.17	-10000	0	-0.49	32	32
PLA2G4A	-0.097	0.24	-10000	0	-0.57	51	51
GNA14	-0.083	0.22	-10000	0	-0.59	68	68
GNA15	0.01	0.042	-10000	0	-0.59	2	2
GNA12	0.006	0.08	-10000	0	-0.82	4	4
GNA11	0.009	0.051	-10000	0	-0.59	3	3
Rac1/GTP	-0.11	0.36	0.34	113	-0.65	59	172
MMP1	-0.56	0.24	-10000	0	-0.65	375	375

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.019	0.089	-9999	-0.44	18	18
Necdin/E2F1	-0.046	0.16	-9999	-0.6	32	32
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.11	0.2	-9999	-0.48	83	83
NGF (dimer)/p75(NTR)/BEX1	-0.15	0.25	-9999	-0.57	105	105
NT-4/5 (dimer)/p75(NTR)	-0.029	0.13	-9999	-0.58	21	21
IKBKB	0.014	0	-9999	-10000	0	0
AKT1	-0.069	0.2	-9999	-0.46	82	82
IKBKG	0.014	0	-9999	-10000	0	0
BDNF	-0.042	0.2	-9999	-0.71	33	33
MGDIs/NGR/p75(NTR)/LINGO1	-0.086	0.22	-9999	-0.61	55	55
FURIN	0.014	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.072	0.17	-9999	-0.56	32	32
LINGO1	-0.053	0.23	-9999	-0.82	34	34
Sortilin/TRAF6/NRIF	-0.011	0.054	-9999	-10000	0	0
proBDNF (dimer)	-0.042	0.2	-9999	-0.71	33	33
NTRK1	-0.055	0.23	-9999	-0.82	35	35
RTN4R	-0.018	0.16	-9999	-0.82	16	16
neuron apoptosis	-0.062	0.19	-9999	-0.57	22	22
IRAK1	0.014	0	-9999	-10000	0	0
SHC1	-0.096	0.23	-9999	-0.55	82	82
ARHGDIA	0.014	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.022	-9999	-0.46	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.12	0.21	-9999	-0.51	83	83
MAGEH1	0.012	0.04	-9999	-0.82	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.13	0.22	-9999	-0.53	85	85
Mammalian IAPs/DIABLO	-0.026	0.13	-9999	-0.59	19	19
proNGF (dimer)	-0.14	0.31	-9999	-0.8	78	78
MAGED1	0.007	0.07	-9999	-0.7	4	4
APP	0.012	0.04	-9999	-0.82	1	1
NT-4/5 (dimer)	0.01	0.05	-9999	-0.7	2	2
ZNF274	0.014	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.076	0.2	-9999	-0.47	82	82
NGF	-0.14	0.32	-9999	-0.8	78	78
cell cycle arrest	-0.1	0.22	-9999	-0.51	82	82
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.03	0.13	-9999	-0.59	2	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.026	0.12	-9999	-0.61	14	14
NCSTN	0.014	0	-9999	-10000	0	0
mol:GTP	-0.12	0.22	-9999	-0.54	82	82
PSENEN	0.012	0.04	-9999	-0.82	1	1
mol:ceramide	-0.093	0.22	-9999	-0.5	82	82
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.01	0.1	-9999	-0.42	2	2
p75(NTR)/beta APP	-0.028	0.12	-9999	-0.54	22	22
BEX1	-0.042	0.2	-9999	-0.82	27	27
mol:GDP	-0.11	0.23	-9999	-0.52	98	98
NGF (dimer)	-0.18	0.26	-9999	-0.55	124	124
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.078	0.2	-9999	-0.56	55	55
PIK3R1	0.009	0.051	-9999	-0.59	3	3
RAC1/GTP	-0.1	0.19	-9999	-0.48	82	82
MYD88	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.22	-9999	-0.55	82	82
RHOB	0.014	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.038	0.15	-9999	-0.63	26	26
NT3 (dimer)	-0.18	0.28	-9999	-0.59	135	135
TP53	-0.019	0.16	-9999	-0.6	5	5
PRDM4	-0.093	0.22	-9999	-0.51	82	82
BDNF (dimer)	-0.46	0.3	-9999	-0.6	317	317
PIK3CA	0.014	0	-9999	-10000	0	0
SORT1	-0.011	0.12	-9999	-0.59	17	17
activation of caspase activity	-0.11	0.2	-9999	-0.47	83	83
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.12	0.21	-9999	-0.51	83	83
RHOC	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
MAPK10	-0.063	0.2	-9999	-0.54	24	24
DIABLO	0.014	0	-9999	-10000	0	0
SMPD2	-0.093	0.22	-9999	-0.51	82	82
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.13	0.23	-9999	-0.56	82	82
PSEN1	0.014	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.021	-9999	-0.43	1	1
NT3 (dimer)/p75(NTR)	-0.16	0.23	-9999	-0.46	149	149
MAPK8	-0.055	0.19	-9999	-0.56	16	16
MAPK9	-0.051	0.19	-9999	-0.55	15	15
APAF1	0.012	0.029	-9999	-0.59	1	1
NTF3	-0.18	0.28	-9999	-0.59	135	135
NTF4	0.01	0.05	-9999	-0.7	2	2
NDN	0.003	0.082	-9999	-0.62	7	7
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.092	0.17	-9999	-0.86	1	1
p75 CTF/Sortilin/TRAF6/NRIF	-0.015	0.069	-9999	-0.49	1	1
RhoA-B-C/GTP	-0.12	0.22	-9999	-0.54	82	82
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.061	0.15	-9999	-0.48	33	33
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.066	0.16	-9999	-0.51	33	33
PRKACB	0.014	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.043	0.15	-9999	-0.52	35	35
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.016	0.15	-9999	-0.82	15	15
BIRC2	-0.002	0.11	-9999	-0.82	8	8
neuron projection morphogenesis	-0.099	0.2	-9999	-0.46	82	82
BAD	-0.048	0.19	-9999	-0.53	15	15
RIPK2	0.014	0	-9999	-10000	0	0
NGFR	-0.023	0.16	-9999	-0.72	21	21
CYCS	-0.084	0.22	-9999	-0.48	82	82
ADAM17	0.011	0.041	-9999	-0.59	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.11	0.2	-9999	-0.5	83	83
BCL2L11	-0.048	0.19	-9999	-0.53	15	15
BDNF (dimer)/p75(NTR)	-0.068	0.18	-9999	-0.53	54	54
PI3K	-0.11	0.2	-9999	-0.5	82	82
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.12	0.21	-9999	-0.51	82	82
NDNL2	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
PRKCI	0.014	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.26	-9999	-0.6	98	98
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.12	0.22	-9999	-0.52	82	82
TRAF6	0.012	0.04	-9999	-0.82	1	1
RAC1	0.014	0	-9999	-10000	0	0
PRKCZ	0.012	0.029	-9999	-0.59	1	1
PLG	-0.006	0.079	-9999	-0.82	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.1	0.22	-9999	-0.61	27	27
SQSTM1	0.014	0	-9999	-10000	0	0
NGFRAP1	0.01	0.057	-9999	-0.82	2	2
CASP3	-0.041	0.17	-9999	-0.48	15	15
E2F1	-0.037	0.2	-9999	-0.82	26	26
CASP9	0.014	0	-9999	-10000	0	0
IKK complex	-0.1	0.16	-9999	-0.69	4	4
NGF (dimer)/TRKA	-0.16	0.28	-9999	-0.63	110	110
MMP7	-0.13	0.3	-9999	-0.76	79	79
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.11	0.2	-9999	-0.48	83	83
MMP3	-0.56	0.38	-9999	-0.81	295	295
APAF-1/Caspase 9	-0.1	0.17	-9999	-0.69	14	14

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.23	0.38	-9999	-1.1	39	39
PCK1	-0.51	0.62	-9999	-1.3	150	150
HNF4A	-0.29	0.47	-9999	-1.3	50	50
KCNJ11	-0.33	0.51	-9999	-1.1	90	90
AKT1	-0.075	0.15	-9999	-10000	0	0
response to starvation	-0.004	0.024	-9999	-10000	0	0
DLK1	-0.43	0.57	-9999	-1.1	139	139
NKX2-1	-0.069	0.33	-9999	-0.84	35	35
ACADM	-0.23	0.39	-9999	-1.1	41	41
TAT	-0.14	0.24	-9999	-0.87	17	17
CEBPB	0.015	0.004	-9999	-10000	0	0
CEBPA	0.01	0.051	-9999	-0.59	3	3
TTR	-0.3	0.34	-9999	-0.98	52	52
PKLR	-0.26	0.43	-9999	-1.1	59	59
APOA1	-0.27	0.45	-9999	-1.3	36	36
CPT1C	-0.23	0.39	-9999	-1.1	41	41
ALAS1	-0.079	0.17	-9999	-10000	0	0
TFRC	-0.2	0.3	-9999	-0.88	32	32
FOXF1	0.017	0.094	-9999	-0.7	5	5
NF1	0.021	0	-9999	-10000	0	0
HNF1A (dimer)	0	0.11	-9999	-0.81	7	7
CPT1A	-0.23	0.39	-9999	-1.1	38	38
HMGCS1	-0.23	0.38	-9999	-1.1	38	38
NR3C1	0.017	0.026	-9999	-10000	0	0
CPT1B	-0.23	0.4	-9999	-1.1	43	43
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.012	0.027	-9999	-10000	0	0
GCK	-0.26	0.41	-9999	-1.1	45	45
CREB1	-0.041	0.086	-9999	-10000	0	0
IGFBP1	-0.1	0.21	-9999	-0.88	15	15
PDX1	-0.11	0.22	-9999	-0.83	14	14
UCP2	-0.23	0.39	-9999	-1.1	39	39
ALDOB	-0.25	0.43	-9999	-1.2	45	45
AFP	-0.2	0.24	-9999	-0.65	54	54
BDH1	-0.23	0.39	-9999	-1.1	39	39
HADH	-0.24	0.4	-9999	-1.1	41	41
F2	-0.3	0.46	-9999	-1.4	39	39
HNF1A	0	0.11	-9999	-0.81	7	7
G6PC	-0.054	0.13	-9999	-0.7	2	2
SLC2A2	-0.13	0.21	-9999	-0.74	3	3
INS	-0.011	0.063	-9999	-0.84	2	2
FOXA1	-0.24	0.32	-9999	-0.6	173	173
FOXA3	-0.12	0.25	-9999	-0.82	36	36
FOXA2	-0.28	0.46	-9999	-1.2	47	47
ABCC8	-0.24	0.41	-9999	-1.1	43	43
ALB	-0.23	0.3	-9999	-0.79	69	69

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.004	0.053	-9999	-0.64	3	3
Metarhodopsin II/Arrestin	-0.007	0.06	-9999	-0.56	5	5
PDE6G/GNAT1/GTP	-0.021	0.1	-9999	-0.55	16	16
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.001	0.069	-9999	-0.82	3	3
GRK1	0.001	0.04	-9999	-0.82	1	1
CNG Channel	-0.43	0.29	-9999	-0.74	156	156
mol:Na +	-0.32	0.26	-9999	-0.8	51	51
mol:ADP	0.001	0.04	-9999	-0.82	1	1
RGS9-1/Gbeta5/R9AP	-0.019	0.088	-9999	-0.54	6	6
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.33	0.27	-9999	-0.84	51	51
CNGB1	-0.45	0.41	-9999	-0.81	236	236
RDH5	0.012	0.029	-9999	-0.59	1	1
SAG	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.29	0.27	-9999	-0.77	51	51
Na + (4 Units)	-0.3	0.24	-9999	-0.74	51	51
RGS9	0	0.1	-9999	-0.78	7	7
GNB1/GNGT1	-0.1	0.23	-9999	-0.63	70	70
GNAT1/GDP	-0.019	0.095	-9999	-0.6	7	7
GUCY2D	-0.03	0.18	-9999	-0.82	22	22
GNGT1	-0.12	0.31	-9999	-0.82	70	70
GUCY2F	0.001	0.04	-9999	-0.82	1	1
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.18	0.22	-9999	-0.61	42	42
mol:11-cis-retinal	0.012	0.029	-9999	-0.59	1	1
mol:cGMP	-0.081	0.19	-9999	-0.5	67	67
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.008	0.071	-9999	-0.59	6	6
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.028	0.15	-9999	-0.59	29	29
Metarhodopsin II	-0.007	0.06	-9999	-0.51	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.085	0.2	-9999	-0.53	66	66
RGS9BP	-0.004	0.1	-9999	-0.59	12	12
Metarhodopsin II/Transducin	-0.036	0.12	-9999	-0.28	77	77
GCAP Family/Ca ++	-0.06	0.16	-9999	-0.5	51	51
PDE6A/B	-0.24	0.25	-9999	-0.47	217	217
mol:Pi	-0.018	0.087	-9999	-0.54	6	6
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.086	0.19	-9999	-0.5	73	73
PDE6B	-0.04	0.19	-9999	-0.68	33	33
PDE6A	-0.28	0.3	-9999	-0.59	202	202
PDE6G	-0.012	0.14	-9999	-0.82	13	13
RHO	-0.006	0.089	-9999	-0.82	5	5
PDE6	-0.18	0.2	-9999	-0.64	32	32
GUCA1A	-0.079	0.26	-9999	-0.82	47	47
GC2/GCAP Family	-0.061	0.16	-9999	-0.51	48	48
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.006	0.065	-9999	-0.59	5	5

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	-0.014	0.036	-9999	-10000	0	0
NFATC2	-0.059	0.13	-9999	-0.41	45	45
NFATC3	-0.014	0.036	-9999	-10000	0	0
CD40LG	-0.33	0.35	-9999	-0.86	89	89
PTGS2	-0.35	0.37	-9999	-0.87	106	106
JUNB	0.014	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.017	0.016	-9999	-10000	0	0
CaM/Ca2+	-0.016	0.016	-9999	-10000	0	0
CALM1	0.004	0.011	-9999	-10000	0	0
JUN	0.004	0.011	-9999	-10000	0	0
mol:Ca2+	-0.017	0.014	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.004	-9999	-10000	0	0
FOSL1	-0.007	0.13	-9999	-0.8	11	11
CREM	0.013	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.16	0.15	-9999	-0.6	17	17
FOS	-0.078	0.21	-9999	-0.6	57	57
IFNG	-0.37	0.38	-9999	-0.87	120	120
AP-1/NFAT1-c-4	-0.39	0.38	-9999	-0.86	121	121
FASLG	-0.32	0.35	-9999	-0.88	77	77
NFAT1-c-4/ICER1	-0.1	0.12	-9999	-0.49	15	15
IL2RA	-0.33	0.36	-9999	-0.88	83	83
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.5	0.42	-9999	-0.82	243	243
JunB/Fra1/NFAT1-c-4	-0.1	0.14	-9999	-0.57	16	16
IL4	-0.3	0.31	-9999	-0.81	66	66
IL2	-0.011	0.037	-9999	-0.68	1	1
IL3	-0.029	0.023	-9999	-10000	0	0
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	0.01	0.057	-9999	-0.82	2	2
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.002	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.28	0.24	-10000	0	-0.92	15	15
IHH	-0.056	0.07	-10000	0	-0.77	2	2
SHH Np/Cholesterol/GAS1	-0.045	0.14	-10000	0	-0.5	35	35
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.045	0.14	0.5	35	-10000	0	35
SMO/beta Arrestin2	-0.15	0.16	-10000	0	-0.6	21	21
SMO	-0.16	0.17	-10000	0	-0.64	21	21
AKT1	-0.065	0.095	-10000	0	-0.73	3	3
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	-0.038	0.17	-10000	0	-0.6	36	36
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.16	0.16	-10000	0	-0.63	21	21
STIL	-0.14	0.17	-10000	0	-0.62	29	29
DHH N/PTCH2	-0.016	0.094	-10000	0	-0.54	13	13
DHH N/PTCH1	-0.14	0.14	-10000	0	-0.74	9	9
PIK3CA	0.014	0	-10000	0	-10000	0	0
DHH	0.008	0.057	-10000	0	-0.82	2	2
PTHLH	-0.47	0.34	-10000	0	-0.66	308	308
determination of left/right symmetry	-0.16	0.16	-10000	0	-0.63	21	21
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
skeletal system development	-0.46	0.33	-10000	0	-0.66	308	308
IHH N/Hhip	-0.055	0.17	-10000	0	-0.68	27	27
DHH N/Hhip	-0.039	0.15	-10000	0	-0.62	27	27
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.16	0.16	-10000	0	-0.63	21	21
pancreas development	-0.037	0.19	-10000	0	-0.81	25	25
HHAT	0.011	0.041	-10000	0	-0.59	2	2
PI3K	-0.003	0.036	-10000	0	-0.43	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.003	0.086	-10000	0	-0.7	6	6
somite specification	-0.16	0.16	-10000	0	-0.63	21	21
SHH Np/Cholesterol/PTCH1	-0.15	0.18	-10000	0	-0.6	40	40
SHH Np/Cholesterol/PTCH2	-0.05	0.16	-10000	0	-0.54	34	34
SHH Np/Cholesterol/Megalin	-0.067	0.19	-10000	0	-0.56	50	50
SHH	-0.032	0.17	-10000	0	-0.62	34	34
catabolic process	-0.17	0.16	-10000	0	-0.68	12	12
SMO/Vitamin D3	-0.16	0.18	-10000	0	-0.64	31	31
SHH Np/Cholesterol/Hhip	-0.068	0.19	-10000	0	-0.58	48	48
LRP2	-0.036	0.19	-10000	0	-0.82	24	24
receptor-mediated endocytosis	-0.18	0.18	-10000	0	-0.65	37	37
SHH Np/Cholesterol/BOC	-0.067	0.16	-10000	0	-0.45	49	49
SHH Np/Cholesterol/CDO	-0.047	0.14	-10000	0	-0.5	33	33
mesenchymal cell differentiation	0.067	0.19	0.57	48	-10000	0	48
mol:Vitamin D3	-0.15	0.18	-10000	0	-0.6	40	40
IHH N/PTCH2	-0.027	0.1	-10000	0	-0.58	13	13
CDON	-0.001	0.092	-10000	0	-0.59	10	10
IHH N/PTCH1	-0.17	0.16	-10000	0	-0.68	12	12
Megalin/LRPAP1	-0.035	0.14	-10000	0	-0.63	24	24
PTCH2	-0.005	0.11	-10000	0	-0.69	11	11
SHH Np/Cholesterol	-0.036	0.14	-10000	0	-0.5	34	34
PTCH1	-0.17	0.16	-10000	0	-0.68	12	12
HHIP	-0.037	0.19	-10000	0	-0.81	25	25

×

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	-0.54	180	180
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.056	0.22	-9999	-0.73	39	39
SMAD9	-0.075	0.16	-9999	-0.6	28	28
SMAD4	0.012	0.029	-9999	-0.59	1	1
SMAD5	-0.053	0.15	-9999	-0.51	22	22
BMP7/USAG1	-0.16	0.25	-9999	-0.51	136	136
SMAD5/SKI	-0.043	0.14	-9999	-0.5	17	17
SMAD1	0.041	0.029	-9999	-10000	0	0
BMP2	-0.019	0.16	-9999	-0.8	17	17
SMAD1/SMAD1/SMAD4	0	0.013	-9999	-10000	0	0
BMPR1A	0.012	0.029	-9999	-0.59	1	1
BMPR1B	-0.07	0.24	-9999	-0.77	45	45
BMPR1A-1B/BAMBI	-0.073	0.18	-9999	-0.56	44	44
AHSG	-0.049	0.21	-9999	-0.82	30	30
CER1	-0.006	0.089	-9999	-0.82	5	5
BMP2-4/CER1	-0.037	0.13	-9999	-0.51	30	30
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.094	0.2	-9999	-0.57	39	39
BMP2-4 (homodimer)	-0.035	0.14	-9999	-0.57	26	26
RGMB	0.014	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.055	0.15	-9999	-0.5	41	41
RGMA	-0.06	0.2	-9999	-0.6	51	51
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.094	0.19	-9999	-0.52	40	40
BMP2-4/USAG1	-0.14	0.21	-9999	-0.59	45	45
SMAD6/SMURF1/SMAD5	-0.043	0.14	-9999	-0.5	17	17
SOSTDC1	-0.17	0.3	-9999	-0.64	120	120
BMP7/BMPR2/BMPR1A-1B	-0.073	0.16	-9999	-0.51	39	39
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.085	-9999	-0.77	5	5
HFE2	-0.17	0.27	-9999	-0.59	125	125
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.052	0.16	-9999	-0.55	35	35
SMAD5/SMAD5/SMAD4	-0.043	0.14	-9999	-0.5	18	18
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.096	0.14	-9999	-0.57	19	19
BMP7 (homodimer)	-0.032	0.16	-9999	-0.6	32	32
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.051	0.17	-9999	-0.62	35	35
SMAD1/SKI	0.047	0.027	-9999	-10000	0	0
SMAD6	0.014	0	-9999	-10000	0	0
CTDSP2	0.014	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.068	0.18	-9999	-0.56	47	47
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.37	0.41	-9999	-0.82	196	196
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.063	0.18	-9999	-0.59	45	45
CHRDL1	-0.27	0.3	-9999	-0.59	201	201
ENDOFIN/SMAD1	0.047	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.001	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	-0.017	0.14	-9999	-0.66	19	19
SMURF2	0.014	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.2	0.22	-9999	-0.72	24	24
BMP2-4/GREM1	-0.28	0.3	-9999	-0.57	202	202
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.046	0.16	-9999	-0.56	29	29
SMAD1/SMAD6	0.047	0.027	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.033	0.16	-9999	-0.6	32	32
BMP6	0.004	0.085	-9999	-0.77	5	5
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.075	0.16	-9999	-0.46	39	39
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.047	0.027	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.18	0.24	-9999	-0.53	99	99
CHRD	-0.021	0.16	-9999	-0.8	18	18
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.1	0.19	-9999	-0.56	40	40
BMP4	-0.001	0.096	-9999	-0.61	10	10
FST	-0.3	0.4	-9999	-0.82	158	158
BMP2-4/NOG	-0.073	0.19	-9999	-0.57	41	41
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.068	0.15	-9999	-0.47	39	39

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.015	0.13	-9999	-0.64	18	18
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.035	0.12	-9999	-0.44	34	34
STXBP1	0.014	0	-9999	-10000	0	0
ACh/CHRNA1	-0.16	0.25	-9999	-0.5	139	139
RAB3GAP2/RIMS1/UNC13B	-0.029	0.1	-9999	-0.54	2	2
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	-0.037	0.16	-9999	-0.6	32	32
mol:ACh	-0.002	0.04	-9999	-0.12	41	41
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.045	0.11	-9999	-0.42	11	11
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.16	0.25	-9999	-0.5	139	139
UNC13B	0.011	0.041	-9999	-0.59	2	2
CHRNA1	-0.23	0.35	-9999	-0.72	139	139
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.14	0.26	-9999	-0.58	107	107
SNAP25	-0.01	0.073	-9999	-0.3	25	25
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.19	0.36	-9999	-0.81	107	107
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.005	0.11	-9999	-0.55	18	18
STX1A/SNAP25 fragment 1/VAMP2	-0.045	0.11	-9999	-0.42	11	11

×

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	-0.072	0.14	-9999	-0.54	2	2
PDGFB-D/PDGFRB/SLAP	-0.13	0.25	-9999	-0.62	92	92
PDGFB-D/PDGFRB/APS/CBL	-0.12	0.22	-9999	-0.53	92	92
AKT1	-0.026	0.17	-9999	-0.6	3	3
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.043	0.16	-9999	-0.56	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
FGR	-0.085	0.17	-9999	-0.4	90	90
mol:Ca2+	-0.042	0.15	-9999	-0.39	1	1
MYC	-0.005	0.12	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.087	0.18	-9999	-0.42	92	92
LRP1/PDGFRB/PDGFB	-0.12	0.23	-9999	-0.55	96	96
GRB10	0.01	0.057	-9999	-0.82	2	2
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	-0.043	0.15	-9999	-0.4	1	1
PTEN	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
GRB7	0.004	0.085	-9999	-0.77	5	5
PDGFB-D/PDGFRB/SHP2	-0.13	0.25	-9999	-0.62	90	90
PDGFB-D/PDGFRB/GRB10	-0.13	0.25	-9999	-0.62	92	92
cell cycle arrest	-0.13	0.25	-9999	-0.61	92	92
HRAS	0.012	0.04	-9999	-0.82	1	1
HIF1A	-0.013	0.16	-9999	-0.52	3	3
GAB1	-0.043	0.15	-9999	-0.39	12	12
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.037	0.15	-9999	-0.47	1	1
PDGFB-D/PDGFRB	-0.11	0.22	-9999	-0.53	91	91
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.13	0.25	-9999	-0.62	90	90
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.074	0.14	-9999	-0.68	1	1
positive regulation of MAPKKK cascade	-0.13	0.25	-9999	-0.61	90	90
PIK3R1	0.009	0.051	-9999	-0.59	3	3
mol:IP3	-0.043	0.15	-9999	-0.4	1	1
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.14	0.26	-9999	-0.62	93	93
SHB	0.009	0.051	-9999	-0.59	3	3
BLK	-0.14	0.2	-9999	-0.44	102	102
PTPN2	0.011	0.04	-9999	-0.81	1	1
PDGFB-D/PDGFRB/SNX15	-0.13	0.25	-9999	-0.62	90	90
BCAR1	0.014	0	-9999	-10000	0	0
VAV2	-0.039	0.15	-9999	-0.43	4	4
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.13	0.25	-9999	-0.62	90	90
LCK	-0.091	0.17	-9999	-0.4	90	90
PDGFRB	-0.16	0.34	-9999	-0.81	90	90
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.086	0.17	-9999	-0.4	92	92
ABL1	-0.052	0.16	-9999	-0.41	13	13
PDGFB-D/PDGFRB/CBL	-0.042	0.15	-9999	-0.41	2	2
PTPN1	0.013	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.039	0.2	-9999	-0.81	27	27
cell proliferation	-0.003	0.11	-9999	-10000	0	0
SLA	0.01	0.057	-9999	-0.82	2	2
actin cytoskeleton reorganization	-0.045	0.19	-9999	-10000	0	0
SRC	-0.084	0.16	-9999	-0.41	12	12
PI3K	-0.085	0.16	-9999	-0.69	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.12	0.22	-9999	-0.54	93	93
SH2B2	0.01	0.057	-9999	-0.82	2	2
PLCgamma1/SPHK1	-0.044	0.16	-9999	-0.59	2	2
LYN	-0.085	0.17	-9999	-0.4	92	92
LRP1	0.012	0.029	-9999	-0.59	1	1
SOS1	0.014	0	-9999	-10000	0	0
STAT5B	0.014	0	-9999	-10000	0	0
STAT5A	0.014	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.089	0.17	-9999	-0.44	1	1
SPHK1	-0.004	0.12	-9999	-0.82	9	9
EDG1	-0.001	0.004	-9999	-10000	0	0
mol:DAG	-0.043	0.15	-9999	-0.4	1	1
PLCG1	-0.045	0.15	-9999	-0.41	1	1
NHERF/PDGFRB	-0.12	0.22	-9999	-0.54	90	90
YES1	-0.084	0.16	-9999	-0.4	90	90
cell migration	-0.12	0.22	-9999	-0.54	90	90
SHC/Grb2/SOS1	-0.089	0.17	-9999	-10000	0	0
SLC9A3R2	0.012	0.04	-9999	-0.82	1	1
SLC9A3R1	0.008	0.058	-9999	-0.59	4	4
NHERF1-2/PDGFRB/PTEN	-0.11	0.2	-9999	-0.49	90	90
FYN	-0.084	0.17	-9999	-0.4	91	91
DOK1	-0.074	0.21	-9999	-0.48	91	91
HRAS/GTP	-0.001	0.031	-9999	-0.64	1	1
PDGFB	-0.004	0.12	-9999	-0.82	9	9
RAC1	-0.023	0.14	-9999	-10000	0	0
PRKCD	-0.073	0.21	-9999	-0.48	91	91
FER	-0.074	0.21	-9999	-0.48	91	91
MAPKKK cascade	-0.088	0.17	-9999	-10000	0	0
RASA1	-0.074	0.21	-9999	-0.48	91	91
NCK1	0.014	0	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	-0.087	0.18	-9999	-0.44	91	91
PDGFB-D/PDGFRB/SHB	-0.13	0.25	-9999	-0.61	93	93
chemotaxis	-0.05	0.16	-9999	-0.4	13	13
STAT1-3-5/STAT1-3-5	-0.11	0.2	-9999	-0.84	7	7
Bovine Papilomavirus E5/PDGFRB	-0.13	0.26	-9999	-0.63	90	90
PTPRJ	0.014	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.012	0.029	-10000	0	-0.59	1	1
EPHB2	-0.15	0.33	-10000	0	-0.82	84	84
EFNB1	-0.024	0.17	-10000	0	-0.63	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.23	-10000	0	-0.84	16	16
Ephrin B2/EPHB1-2	-0.12	0.22	-10000	0	-0.51	102	102
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.8	16	16
Ephrin B1/EPHB1-2/Tiam1	-0.15	0.25	-10000	0	-0.52	119	119
DNM1	-0.048	0.22	-10000	0	-0.82	31	31
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.009	0.089	-10000	0	-0.62	8	8
YES1	-0.015	0.12	-10000	0	-0.86	8	8
Ephrin B1/EPHB1-2/NCK2	-0.14	0.25	-10000	0	-0.52	119	119
PI3K	0.007	0.1	-10000	0	-0.7	8	8
mol:GDP	-0.15	0.25	-10000	0	-0.51	119	119
ITGA2B	-0.053	0.23	-10000	0	-0.82	34	34
endothelial cell proliferation	-0.001	0.018	-10000	0	-0.36	1	1
FYN	-0.015	0.12	-10000	0	-0.86	8	8
MAP3K7	-0.013	0.091	-10000	0	-0.67	8	8
FGR	-0.015	0.12	-10000	0	-0.86	8	8
TIAM1	0.006	0.065	-10000	0	-0.59	5	5
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
RGS3	0.014	0	-10000	0	-10000	0	0
cell adhesion	-0.033	0.19	-10000	0	-0.54	36	36
LYN	-0.015	0.12	-10000	0	-0.88	8	8
Ephrin B1/EPHB1-2/Src Family Kinases	-0.017	0.11	-10000	0	-0.81	8	8
Ephrin B1/EPHB1-2	-0.018	0.099	-10000	0	-0.72	8	8
SRC	-0.015	0.12	-10000	0	-0.86	8	8
ITGB3	-0.022	0.16	-10000	0	-0.74	20	20
EPHB1	-0.037	0.19	-10000	0	-0.74	28	28
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.018	-10000	0	-0.36	1	1
alphaIIb/beta3 Integrin	-0.076	0.21	-10000	0	-0.62	52	52
BLK	-0.032	0.12	-10000	0	-0.86	8	8
HCK	-0.016	0.12	-10000	0	-0.86	8	8
regulation of stress fiber formation	0.14	0.24	0.51	119	-10000	0	119
MAPK8	0.012	0.1	-10000	0	-0.66	8	8
Ephrin B1/EPHB1-2/RGS3	-0.14	0.25	-10000	0	-0.52	119	119
endothelial cell migration	-0.007	0.079	-10000	0	-0.56	8	8
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	-0.003	0.098	-10000	0	-0.7	8	8
regulation of focal adhesion formation	0.14	0.24	0.51	119	-10000	0	119
chemotaxis	0.14	0.24	0.51	119	-10000	0	119
PIK3CA	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.14	0.22	-10000	0	-0.84	16	16
angiogenesis	-0.018	0.098	-10000	0	-0.72	8	8
LCK	-0.017	0.12	-10000	0	-0.86	8	8

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0	0.039	-9999	-0.59	1	1
SVIL	0.003	0.024	-9999	-10000	0	0
ZNF318	0.04	0.061	-9999	-10000	0	0
JMJD2C	0.006	0.024	-9999	-0.11	14	14
T-DHT/AR/Ubc9	-0.12	0.18	-9999	-0.42	108	108
CARM1	0.012	0.003	-9999	-10000	0	0
PRDX1	0.015	0.004	-9999	-10000	0	0
PELP1	0.018	0.01	-9999	-10000	0	0
CTNNB1	0.004	0.034	-9999	-0.59	1	1
AKT1	0.021	0.017	-9999	-10000	0	0
PTK2B	0.005	0.033	-9999	-0.59	1	1
MED1	0.02	0.045	-9999	-0.82	1	1
MAK	0.024	0.12	-9999	-0.65	10	10
response to oxidative stress	0.002	0.004	-9999	-10000	0	0
HIP1	0.002	0.038	-9999	-0.59	1	1
GSN	0.002	0.027	-9999	-10000	0	0
NCOA2	-0.025	0.14	-9999	-0.59	26	26
NCOA6	0.004	0.023	-9999	-10000	0	0
DNA-PK	0.031	0.067	-9999	-10000	0	0
NCOA4	0.011	0.029	-9999	-0.59	1	1
PIAS3	0.005	0.019	-9999	-10000	0	0
cell proliferation	-0.02	0.13	-9999	-0.69	10	10
XRCC5	0.02	0.013	-9999	-10000	0	0
UBE3A	-0.004	0.038	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.13	0.2	-9999	-0.44	121	121
FHL2	-0.026	0.11	-9999	-0.96	2	2
RANBP9	0.004	0.023	-9999	-10000	0	0
JMJD1A	-0.062	0.076	-9999	-0.14	215	215
CDK6	0.001	0.1	-9999	-0.78	7	7
TGFB1I1	-0.025	0.15	-9999	-0.82	14	14
T-DHT/AR/CyclinD1	-0.14	0.2	-9999	-0.45	115	115
XRCC6	0.02	0.013	-9999	-10000	0	0
T-DHT/AR	-0.14	0.21	-9999	-0.52	69	69
CTDSP1	0.011	0.005	-9999	-10000	0	0
CTDSP2	0.032	0.042	-9999	-10000	0	0
BRCA1	0.003	0.024	-9999	-10000	0	0
TCF4	0.027	0.03	-9999	-10000	0	0
CDKN2A	-0.34	0.4	-9999	-0.76	194	194
SRF	0.03	0.023	-9999	-10000	0	0
NKX3-1	-0.14	0.15	-9999	-0.88	5	5
KLK3	-0.22	0.55	-9999	-1.4	76	76
TMF1	0.011	0.005	-9999	-10000	0	0
HNRNPA1	0.025	0.026	-9999	-10000	0	0
AOF2	-0.012	0.027	-9999	-0.071	72	72
APPL1	0.041	0.037	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.11	0.19	-9999	-0.42	98	98
AR	-0.17	0.27	-9999	-0.63	108	108
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	0.013	-9999	-10000	0	0
PA2G4	0.026	0.028	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.099	0.17	-9999	-0.38	101	101
RPS6KA3	-0.001	0.048	-9999	-0.59	2	2
T-DHT/AR/ARA70	-0.12	0.18	-9999	-0.42	109	109
LATS2	0.024	0.022	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.093	0.17	-9999	-0.38	98	98
Cyclin D3/CDK11 p58	0.001	0.005	-9999	-10000	0	0
VAV3	-0.036	0.15	-9999	-0.6	29	29
KLK2	-0.08	0.15	-9999	-0.79	14	14
CASP8	0.017	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.45	81	81
TMPRSS2	-0.53	0.51	-9999	-1	212	212
CCND1	-0.01	0.13	-9999	-0.78	11	11
PIAS1	-0.004	0.038	-9999	-10000	0	0
mol:T-DHT	-0.025	0.035	-9999	-0.066	148	148
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.012	0.058	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.12	0.2	-9999	-0.43	113	113
CMTM2	-0.01	0.14	-9999	-0.81	13	13
SNURF	-0.018	0.13	-9999	-0.59	21	21
ZMIZ1	-0.008	0.045	-9999	-0.7	1	1
CCND3	0.014	0.002	-9999	-10000	0	0
TGIF1	0.025	0.026	-9999	-10000	0	0
FKBP4	0.004	0.023	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.023	0.1	-10000	0	-0.54	10	10
fibroblast growth factor receptor signaling pathway	-0.023	0.099	-10000	0	-0.54	10	10
LAMA1	-0.31	0.4	-10000	0	-0.81	167	167
PRNP	0.012	0.04	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.049	0.14	-10000	0	-0.44	47	47
SMAD2	0.033	0.035	-10000	0	-0.49	1	1
GPC1/PrPc/Cu2+	-0.003	0.042	-10000	0	-0.49	3	3
GPC1/Laminin alpha1	-0.25	0.31	-10000	0	-0.63	167	167
TDGF1	0	0.08	-10000	0	-0.82	4	4
CRIPTO/GPC1	-0.008	0.071	-10000	0	-0.59	6	6
APP/GPC1	-0.004	0.048	-10000	0	-0.56	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.018	0.064	-10000	0	-0.54	5	5
FLT1	0.012	0.04	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.003	0.036	-10000	0	-0.54	1	1
SERPINC1	-0.006	0.12	-10000	0	-0.82	9	9
FYN	0.017	0.069	-10000	0	-0.54	6	6
FGR	0.017	0.069	-10000	0	-0.54	6	6
positive regulation of MAPKKK cascade	0.007	0.11	-10000	0	-0.44	8	8
SLIT2	-0.053	0.19	-10000	0	-0.6	46	46
GPC1/NRG	-0.11	0.24	-10000	0	-0.62	75	75
NRG1	-0.13	0.31	-10000	0	-0.81	73	73
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.01	0.078	-10000	0	-0.62	6	6
LYN	0.018	0.066	-10000	0	-0.54	5	5
mol:Spermine	0.01	0.038	-10000	0	-0.54	2	2
cell growth	-0.023	0.099	-10000	0	-0.54	10	10
BMP signaling pathway	-0.01	0.05	0.7	2	-10000	0	2
SRC	0.018	0.064	-10000	0	-0.54	5	5
TGFBR1	0.014	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.37	0.29	-10000	0	-0.59	268	268
GPC1	0.01	0.05	-10000	0	-0.7	2	2
TGFBR1 (dimer)	0.014	0	-10000	0	-10000	0	0
VEGFA	0.004	0.09	-10000	0	-0.82	5	5
BLK	-0.063	0.2	-10000	0	-0.54	57	57
HCK	0.014	0.086	-10000	0	-0.62	6	6
FGF2	-0.01	0.12	-10000	0	-0.65	15	15
FGFR1	0.004	0.09	-10000	0	-0.82	5	5
VEGFR1 homodimer	0.012	0.04	-10000	0	-0.82	1	1
TGFBR2	0.012	0.029	-10000	0	-0.59	1	1
cell death	-0.004	0.047	-10000	0	-0.56	3	3
ATIII/GPC1	-0.016	0.097	-10000	0	-0.61	11	11
PLA2G2A/GPC1	-0.27	0.21	-10000	0	-0.43	269	269
LCK	0.005	0.11	-10000	0	-0.54	15	15
neuron differentiation	-0.11	0.24	-10000	0	-0.61	75	75
PrPc/Cu2+	-0.001	0.031	-10000	0	-0.64	1	1
APP	0.012	0.04	-10000	0	-0.82	1	1
TGFBR2 (dimer)	0.012	0.029	-10000	0	-0.59	1	1

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.14	0.34	-10000	0	-0.92	65	65
NFATC2	-0.036	0.23	-10000	0	-0.78	23	23
NFATC3	-0.008	0.06	-10000	0	-10000	0	0
CD40LG	-0.36	0.42	-10000	0	-1.1	62	62
ITCH	0.016	0.094	-10000	0	-10000	0	0
CBLB	0.016	0.094	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.34	0.46	-10000	0	-1.1	96	96
JUNB	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.037	0.096	-10000	0	-10000	0	0
T cell anergy	-0.008	0.16	-10000	0	-0.48	16	16
TLE4	-0.008	0.18	-10000	0	-0.7	13	13
Jun/NFAT1-c-4/p21SNFT	-0.16	0.23	-10000	0	-0.99	15	15
AP-1/NFAT1-c-4	-0.37	0.44	-10000	0	-1.1	64	64
IKZF1	-0.018	0.21	-10000	0	-0.8	18	18
T-helper 2 cell differentiation	-0.063	0.23	-10000	0	-0.76	24	24
AP-1/NFAT1	-0.14	0.2	-10000	0	-0.65	30	30
CALM1	0.006	0.061	-10000	0	-10000	0	0
EGR2	-0.06	0.3	-10000	0	-1.5	13	13
EGR3	-0.045	0.25	-10000	0	-1.2	9	9
NFAT1/FOXP3	-0.15	0.36	-10000	0	-0.8	81	81
EGR1	-0.01	0.12	-10000	0	-0.59	17	17
JUN	-0.02	0.035	-10000	0	-10000	0	0
EGR4	-0.081	0.26	-10000	0	-0.8	49	49
mol:Ca2+	-0.009	0.066	-10000	0	-10000	0	0
GBP3	-0.028	0.22	-10000	0	-0.76	25	25
FOSL1	-0.007	0.13	-10000	0	-0.8	11	11
NFAT1-c-4/MAF/IRF4	-0.12	0.25	-10000	0	-1	14	14
DGKA	-0.006	0.17	-10000	0	-0.65	13	13
CREM	0.013	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.22	0.28	-10000	0	-0.99	25	25
CTLA4	-0.18	0.43	-10000	0	-1	72	72
NFAT1-c-4 (dimer)/EGR1	-0.1	0.25	-10000	0	-1	16	16
NFAT1-c-4 (dimer)/EGR4	-0.15	0.28	-10000	0	-0.95	25	25
FOS	-0.1	0.2	-10000	0	-0.62	57	57
IFNG	-0.22	0.34	-10000	0	-0.79	84	84
T cell activation	-0.1	0.2	-10000	0	-0.86	5	5
MAF	0.008	0.058	-10000	0	-0.59	4	4
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.034	0.16	0.74	8	-10000	0	8
TNF	-0.13	0.31	-10000	0	-1	29	29
FASLG	-0.11	0.38	-10000	0	-1.3	25	25
TBX21	-0.038	0.18	-10000	0	-0.76	22	22
BATF3	0.01	0.057	-10000	0	-0.82	2	2
PRKCQ	0.002	0.088	-10000	0	-0.66	7	7
PTPN1	-0.006	0.17	-10000	0	-0.66	12	12
NFAT1-c-4/ICER1	-0.097	0.22	-10000	0	-0.97	14	14
GATA3	-0.012	0.14	-10000	0	-0.78	14	14
T-helper 1 cell differentiation	-0.2	0.35	-10000	0	-0.78	84	84
IL2RA	-0.31	0.39	-10000	0	-0.99	85	85
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.006	0.17	-10000	0	-0.66	12	12
E2F1	-0.03	0.2	-10000	0	-0.81	26	26
PPARG	-0.23	0.3	-10000	0	-0.59	169	169
SLC3A2	-0.006	0.17	-10000	0	-0.66	12	12
IRF4	-0.041	0.2	-10000	0	-0.76	30	30
PTGS2	-0.38	0.45	-10000	0	-1.1	75	75
CSF2	-0.54	0.51	-10000	0	-1.1	166	166
JunB/Fra1/NFAT1-c-4	-0.097	0.23	-10000	0	-1	13	13
IL4	-0.066	0.24	-10000	0	-0.81	23	23
IL5	-0.33	0.38	-10000	0	-1	49	49
IL2	-0.1	0.21	-10000	0	-0.92	4	4
IL3	-0.063	0.051	-10000	0	-10000	0	0
RNF128	-0.041	0.24	-10000	0	-0.66	55	55
NFATC1	-0.035	0.16	-10000	0	-0.74	8	8
CDK4	0.021	0.15	0.64	4	-10000	0	4
PTPRK	-0.006	0.17	-10000	0	-0.66	12	12
IL8	-0.4	0.46	-10000	0	-1.1	100	100
POU2F1	0.014	0.002	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.04	0.057	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.1	0.14	-9999	-0.46	30	30
JUN	-0.064	0.17	-9999	-0.48	31	31
HRAS	0.012	0.04	-9999	-0.82	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.26	-9999	-0.62	78	78
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.006	0.08	-9999	-0.82	4	4
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.25	-9999	-0.62	76	76
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.12	0.21	-9999	-0.61	40	40
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.23	-9999	-0.55	76	76
GRB7	0.004	0.085	-9999	-0.77	5	5
RET51/GFRalpha1/GDNF	-0.17	0.25	-9999	-0.62	76	76
MAPKKK cascade	-0.13	0.19	-9999	-0.63	29	29
BCAR1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.2	-9999	-0.6	37	37
lamellipodium assembly	-0.095	0.13	-9999	-0.41	30	30
RET51/GFRalpha1/GDNF/SHC	-0.17	0.25	-9999	-0.62	76	76
PIK3CA	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.12	0.2	-9999	-0.6	36	36
RET9/GFRalpha1/GDNF/Shank3	-0.12	0.2	-9999	-0.6	36	36
MAPK3	-0.11	0.23	-9999	-0.7	28	28
DOK1	0.014	0	-9999	-10000	0	0
DOK6	-0.005	0.11	-9999	-0.69	11	11
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.093	0.22	-9999	-0.65	28	28
DOK5	-0.016	0.14	-9999	-0.64	19	19
GFRA1	-0.12	0.25	-9999	-0.59	96	96
MAPK8	-0.076	0.18	-9999	-0.51	31	31
HRAS/GTP	-0.15	0.22	-9999	-0.73	29	29
tube development	-0.11	0.19	-9999	-0.57	36	36
MAPK1	-0.11	0.23	-9999	-0.7	28	28
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.06	0.15	-9999	-0.54	13	13
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.004	0.09	-9999	-0.82	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.17	0.24	-9999	-0.58	83	83
SHC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.25	-9999	-0.62	76	76
RET51/GFRalpha1/GDNF/Dok5	-0.18	0.26	-9999	-0.62	87	87
PRKCA	0.012	0.04	-9999	-0.82	1	1
HRAS/GDP	-0.001	0.031	-9999	-0.64	1	1
CREB1	-0.074	0.17	-9999	-0.49	28	28
PIK3R1	0.009	0.051	-9999	-0.59	3	3
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.057	0.15	-9999	-0.53	12	12
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.26	-9999	-0.62	81	81
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.081	0.26	-9999	-0.79	50	50
DOK4	0.014	0	-9999	-10000	0	0
JNK cascade	-0.063	0.16	-9999	-0.47	31	31
RET9/GFRalpha1/GDNF/FRS2	-0.12	0.21	-9999	-0.6	40	40
SHANK3	0.014	0	-9999	-10000	0	0
RASA1	0.012	0.029	-9999	-0.59	1	1
NCK1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.057	0.15	-9999	-0.53	12	12
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.087	0.18	-9999	-0.53	30	30
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.085	0.18	-9999	-0.52	28	28
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.087	0.18	-9999	-0.57	28	28
PI3K	-0.1	0.24	-9999	-0.68	30	30
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.11	0.19	-9999	-0.57	36	36
GRB10	0.01	0.057	-9999	-0.82	2	2
activation of MAPKK activity	-0.082	0.17	-9999	-0.52	30	30
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.26	-9999	-0.62	79	79
GAB1	0.014	0	-9999	-10000	0	0
IRS1	0.011	0.041	-9999	-0.59	2	2
IRS2	0.011	0.041	-9999	-0.59	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.087	0.18	-9999	-0.57	28	28
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.25	-9999	-0.61	77	77
GRB2	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.058	0.23	-9999	-0.82	35	35
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.25	-9999	-0.62	76	76
Rac1/GTP	-0.11	0.16	-9999	-0.51	30	30
RET9/GFRalpha1/GDNF	-0.13	0.22	-9999	-0.46	119	119
GFRalpha1/GDNF	-0.15	0.25	-9999	-0.52	119	119

×

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

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
MAP4K1	-0.021	0.15	-10000	0	-0.43	13	13
CRKL	-0.019	0.15	-10000	0	-0.41	48	48
HRAS	-0.009	0.15	-10000	0	-0.57	7	7
mol:PIP3	-0.034	0.14	-10000	0	-0.41	47	47
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.012	0.029	-10000	0	-0.59	1	1
GAB1	-0.028	0.15	-10000	0	-0.44	47	47
FOXO3	-0.012	0.14	-10000	0	-0.37	42	42
AKT1	-0.022	0.15	-10000	0	-0.4	48	48
BAD	-0.012	0.14	-10000	0	-0.37	47	47
megakaryocyte differentiation	-0.041	0.17	-10000	0	-0.44	59	59
GSK3B	-0.012	0.14	-10000	0	-0.37	47	47
RAF1	0.005	0.13	-10000	0	-0.47	5	5
SHC1	0.014	0	-10000	0	-10000	0	0
STAT3	-0.028	0.15	-10000	0	-0.44	47	47
STAT1	-0.1	0.37	-10000	0	-1.1	47	47
HRAS/SPRED1	-0.048	0.1	-10000	0	-0.47	5	5
cell proliferation	-0.032	0.16	-10000	0	-0.45	47	47
PIK3CA	0.014	0	-10000	0	-10000	0	0
TEC	-0.022	0.14	-10000	0	-0.59	25	25
RPS6KB1	-0.028	0.15	-10000	0	-0.43	47	47
HRAS/SPRED2	-0.048	0.1	-10000	0	-0.46	7	7
LYN/TEC/p62DOK	-0.069	0.15	-10000	0	-0.59	15	15
MAPK3	0.019	0.098	-10000	0	-0.34	3	3
STAP1	-0.062	0.19	-10000	0	-0.44	77	77
GRAP2	-0.003	0.11	-10000	0	-0.7	10	10
JAK2	-0.12	0.27	-10000	0	-0.84	47	47
STAT1 (dimer)	-0.099	0.36	-10000	0	-1	47	47
mol:Gleevec	0	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.081	0.16	-10000	0	-0.51	19	19
actin filament polymerization	-0.029	0.16	-10000	0	-0.44	48	48
LYN	0.012	0.029	-10000	0	-0.59	1	1
STAP1/STAT5A (dimer)	-0.069	0.23	-10000	0	-0.6	51	51
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
CBL/CRKL/GRB2	-0.042	0.12	-10000	0	-0.56	1	1
PI3K	-0.015	0.16	-10000	0	-0.42	47	47
PTEN	0.014	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.14	0.44	-10000	0	-1.3	48	48
MAPK8	-0.033	0.17	-10000	0	-0.46	47	47
STAT3 (dimer)	-0.027	0.15	-10000	0	-0.43	47	47
positive regulation of transcription	0.021	0.084	-10000	0	-10000	0	0
mol:GDP	-0.069	0.14	-10000	0	-0.64	7	7
PIK3C2B	-0.029	0.16	-10000	0	-0.45	47	47
CBL/CRKL	-0.01	0.14	-10000	0	-0.43	6	6
FER	-0.029	0.16	-10000	0	-0.44	47	47
SH2B3	-0.029	0.16	-10000	0	-0.44	48	48
PDPK1	-0.023	0.13	-10000	0	-0.37	47	47
SNAI2	-0.039	0.17	-10000	0	-0.44	56	56
positive regulation of cell proliferation	-0.06	0.26	-10000	0	-0.74	47	47
KITLG	0.01	0.053	-10000	0	-0.61	3	3
cell motility	-0.06	0.26	-10000	0	-0.74	47	47
PTPN6	0.008	0.013	-10000	0	-10000	0	0
EPOR	-0.001	0.14	-10000	0	-0.65	8	8
STAT5A (dimer)	-0.043	0.22	-10000	0	-0.6	47	47
SOCS1	-0.035	0.2	-10000	0	-0.82	25	25
cell migration	0.038	0.17	0.44	55	-10000	0	55
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.074	0.25	-10000	0	-0.81	44	44
VAV1	0.005	0.071	-10000	0	-0.59	6	6
GRB10	-0.03	0.16	-10000	0	-0.44	49	49
PTPN11	0.014	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.038	0.16	-10000	0	-0.46	49	49
GO:0007205	0.001	0.009	-10000	0	-10000	0	0
MAP2K1	0.015	0.11	-10000	0	-0.37	3	3
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.11	0.43	-10000	0	-1.3	48	48
MAP2K2	0.015	0.11	-10000	0	-0.37	3	3
SHC/Grb2/SOS1	-0.053	0.13	-10000	0	-0.48	4	4
STAT5A	-0.045	0.22	-10000	0	-0.62	47	47
GRB2	0.014	0	-10000	0	-10000	0	0
response to radiation	-0.038	0.17	-10000	0	-0.44	56	56
SHC/GRAP2	-0.012	0.081	-10000	0	-0.53	10	10
PTPRO	-0.042	0.17	-10000	0	-0.44	59	59
SH2B2	-0.03	0.16	-10000	0	-0.44	48	48
DOK1	0.014	0	-10000	0	-10000	0	0
MATK	-0.039	0.17	-10000	0	-0.45	55	55
CREBBP	0.034	0.015	-10000	0	-10000	0	0
BCL2	-0.006	0.18	-10000	0	-1	8	8

×

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	-0.083	0.22	-10000	0	-0.55	49	49
TBX21	-0.13	0.45	-10000	0	-1.2	44	44
B2M	0.012	0.01	-10000	0	-10000	0	0
TYK2	0.016	0.046	-10000	0	-0.84	1	1
IL12RB1	-0.058	0.25	-10000	0	-0.83	39	39
GADD45B	-0.054	0.29	-10000	0	-0.84	18	18
IL12RB2	-0.13	0.32	-10000	0	-0.79	77	77
GADD45G	-0.066	0.32	-10000	0	-0.84	30	30
natural killer cell activation	0.006	0.024	-10000	0	-10000	0	0
RELB	0.008	0.07	-10000	0	-0.82	3	3
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.005	0.11	-10000	0	-0.59	15	15
IL2RA	-0.067	0.24	-10000	0	-0.82	41	41
IFNG	-0.16	0.34	-10000	0	-0.82	88	88
STAT3 (dimer)	-0.075	0.32	-10000	0	-0.8	43	43
HLA-DRB5	-0.004	0.11	-10000	0	-0.69	10	10
FASLG	-0.14	0.46	-10000	0	-1.2	51	51
NF kappa B2 p52/RelB	-0.2	0.34	-10000	0	-0.97	56	56
CD4	0.01	0.05	-10000	0	-0.71	2	2
SOCS1	-0.035	0.2	-10000	0	-0.82	25	25
EntrezGene:6955	-0.005	0.016	-10000	0	-10000	0	0
CD3D	-0.006	0.11	-10000	0	-0.71	10	10
CD3E	-0.005	0.11	-10000	0	-0.76	9	9
CD3G	-0.028	0.16	-10000	0	-0.7	23	23
IL12Rbeta2/JAK2	-0.085	0.25	-10000	0	-0.6	78	78
CCL3	-0.13	0.43	-10000	0	-1.1	46	46
CCL4	-0.12	0.42	-10000	0	-1.1	44	44
HLA-A	0.002	0.085	-10000	0	-0.77	5	5
IL18/IL18R	0.028	0.13	-10000	0	-0.49	18	18
NOS2	-0.14	0.43	-10000	0	-1	53	53
IL12/IL12R/TYK2/JAK2/SPHK2	-0.065	0.21	-10000	0	-0.54	41	41
IL1R1	-0.11	0.4	-10000	0	-1.1	42	42
IL4	-0.005	0.024	-10000	0	-10000	0	0
JAK2	0.017	0.037	-10000	0	-0.61	1	1
EntrezGene:6957	-0.005	0.016	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.097	0.32	-10000	0	-0.83	50	50
RAB7A	-0.031	0.27	-10000	0	-0.74	14	14
lysosomal transport	-0.027	0.26	-10000	0	-0.69	15	15
FOS	-0.17	0.49	-10000	0	-1.2	65	65
STAT4 (dimer)	-0.074	0.35	-10000	0	-0.88	40	40
STAT5A (dimer)	-0.27	0.42	-10000	0	-1	80	80
GZMA	-0.15	0.48	-10000	0	-1.2	52	52
GZMB	-0.16	0.47	-10000	0	-1.1	61	61
HLX	0.008	0.07	-10000	0	-0.82	3	3
LCK	-0.14	0.45	-10000	0	-1.1	50	50
TCR/CD3/MHC II/CD4	-0.031	0.19	-10000	0	-0.57	30	30
IL2/IL2R	-0.073	0.21	-10000	0	-0.6	51	51
MAPK14	-0.054	0.31	-10000	0	-0.82	26	26
CCR5	-0.074	0.34	-10000	0	-1.1	22	22
IL1B	-0.07	0.26	-10000	0	-0.8	46	46
STAT6	-0.01	0.12	-10000	0	-10000	0	0
STAT4	-0.002	0.11	-10000	0	-0.79	8	8
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.039	0.2	-10000	0	-0.81	27	27
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.014	0	-10000	0	-10000	0	0
IL12B	-0.058	0.24	-10000	0	-0.82	39	39
CD8A	-0.05	0.21	-10000	0	-0.74	35	35
CD8B	-0.066	0.23	-10000	0	-0.74	44	44
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.082	0.22	0.55	49	-10000	0	49
IL2RB	-0.002	0.11	-10000	0	-0.79	8	8
proteasomal ubiquitin-dependent protein catabolic process	-0.063	0.32	-10000	0	-0.81	36	36
IL2RG	-0.013	0.15	-10000	0	-0.8	14	14
IL12	-0.047	0.21	-10000	0	-0.59	54	54
STAT5A	0.014	0	-10000	0	-10000	0	0
CD247	-0.021	0.16	-10000	0	-0.79	17	17
IL2	0.003	0.04	-10000	0	-0.82	1	1
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.005	0.12	-10000	0	-0.62	15	15
IL12/IL12R/TYK2/JAK2	-0.15	0.49	-10000	0	-1.2	56	56
MAP2K3	-0.054	0.31	-10000	0	-0.8	28	28
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.065	0.32	-10000	0	-0.83	30	30
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.065	-10000	0	-0.65	4	4
IL18RAP	-0.003	0.12	-10000	0	-0.69	12	12
IL12Rbeta1/TYK2	-0.036	0.2	-10000	0	-0.65	40	40
EOMES	-0.084	0.26	-10000	0	-0.68	55	55
STAT1 (dimer)	-0.14	0.38	-10000	0	-0.85	66	66
T cell proliferation	-0.027	0.26	0.42	1	-0.65	25	26
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.011	0.066	-10000	0	-0.76	3	3
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.22	-10000	0	-0.73	26	26
ATF2	-0.041	0.29	-10000	0	-0.79	21	21

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.015	0.081	-9999	-0.48	11	11
RGS9BP	-0.004	0.1	-9999	-0.59	12	12
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.001	0.04	-9999	-0.82	1	1
mol:Na +	-0.1	0.21	-9999	-0.55	77	77
mol:ADP	-0.055	0.2	-9999	-0.63	45	45
GNAT2	0.012	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.019	0.088	-9999	-0.54	6	6
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.074	0.25	-9999	-0.82	44	44
CNGB3	-0.14	0.32	-9999	-0.82	76	76
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.18	0.29	-9999	-0.56	150	150
Cone PDE6	-0.016	0.075	-9999	-0.47	6	6
Cone Metarhodopsin II	-0.055	0.16	-9999	-0.51	45	45
Na + (4 Units)	-0.2	0.28	-9999	-0.56	150	150
GNAT2/GDP	-0.016	0.075	-9999	-0.47	6	6
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.01	0.006	-9999	-10000	0	0
Cone Transducin	-0.016	0.085	-9999	-0.5	11	11
SLC24A2	-0.17	0.34	-9999	-0.82	92	92
GNB3/GNGT2	-0.02	0.11	-9999	-0.57	15	15
GNB3	-0.009	0.13	-9999	-0.78	12	12
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.006	0.041	-9999	-0.82	1	1
ARR3	0.002	0.004	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.21	-9999	-0.55	77	77
mol:Pi	-0.018	0.087	-9999	-0.54	6	6
Cone CNG Channel	-0.083	0.18	-9999	-0.46	77	77
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.17	0.34	-9999	-0.82	92	92
RGS9	0	0.1	-9999	-0.78	7	7
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	0.009	0.058	-9999	-0.67	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.005	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.014	0.064	-10000	0	-10000	0	0
SMARCC2	0.015	0.007	-10000	0	-10000	0	0
SMARCC1	0.015	0.007	-10000	0	-10000	0	0
TBX21	-0.097	0.23	-10000	0	-0.85	28	28
SUMO2	0.014	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	-0.029	0.2	-10000	0	-0.8	27	27
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	0.011	0.041	-10000	0	-0.59	2	2
GR alpha/HSP90/FKBP51/HSP90	0.098	0.097	0.36	9	-10000	0	9
PRL	-0.1	0.17	-10000	0	-0.66	13	13
cortisol/GR alpha (dimer)/TIF2	0.19	0.24	0.59	55	-10000	0	55
RELA	-0.003	0.091	-10000	0	-10000	0	0
FGG	0.12	0.26	0.55	24	-0.67	24	48
GR beta/TIF2	0.074	0.14	0.38	12	-0.4	7	19
IFNG	-0.37	0.33	-10000	0	-0.86	112	112
apoptosis	0.028	0.18	0.54	7	-0.66	4	11
CREB1	0.016	0.019	-10000	0	-10000	0	0
histone acetylation	0	0.12	0.42	4	-0.43	9	13
BGLAP	-0.055	0.15	-10000	0	-0.87	6	6
GR/PKAc	0.096	0.092	0.34	9	-0.43	1	10
NF kappa B1 p50/RelA	-0.014	0.16	-10000	0	-0.46	7	7
SMARCD1	0.015	0.007	-10000	0	-10000	0	0
MDM2	0.083	0.084	0.3	17	-10000	0	17
GATA3	-0.008	0.14	-10000	0	-0.78	14	14
AKT1	0	0.001	-10000	0	-10000	0	0
CSF2	-0.31	0.28	-10000	0	-0.57	219	219
GSK3B	0.014	0.008	-10000	0	-10000	0	0
NR1I3	0.056	0.17	0.62	2	-0.87	2	4
CSN2	0.13	0.15	0.45	15	-0.54	2	17
BRG1/BAF155/BAF170/BAF60A	0.033	0.029	-10000	0	-10000	0	0
NFATC1	0.015	0.003	-10000	0	-10000	0	0
POU2F1	0.015	0.016	-10000	0	-10000	0	0
CDKN1A	0.03	0.04	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	-10000	0	-10000	0	0
SFN	0.007	0.07	-10000	0	-0.7	4	4
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.097	0.099	0.4	3	-0.44	1	4
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.036	0.22	0.52	5	-0.86	17	22
JUN	-0.22	0.18	-10000	0	-0.66	32	32
IL4	-0.071	0.12	-10000	0	-0.54	4	4
CDK5R1	0.012	0.041	-10000	0	-0.82	1	1
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.15	0.31	-10000	0	-0.65	67	67
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.1	0.093	0.37	5	-10000	0	5
cortisol/GR alpha (monomer)	0.25	0.27	0.69	71	-10000	0	71
NCOA2	-0.023	0.14	-10000	0	-0.59	26	26
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.15	0.2	-10000	0	-0.66	57	57
AP-1/NFAT1-c-4	-0.42	0.27	-10000	0	-0.82	87	87
AFP	-0.16	0.2	-10000	0	-0.86	22	22
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.12	0.17	0.51	10	-10000	0	10
TP53	0.032	0.059	-10000	0	-0.57	4	4
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.4	0.39	-10000	0	-0.98	117	117
KRT14	-0.23	0.37	-10000	0	-1.1	60	60
TBP	0.021	0.024	-10000	0	-10000	0	0
CREBBP	0.074	0.085	0.31	20	-10000	0	20
HDAC1	0.012	0.011	-10000	0	-10000	0	0
HDAC2	0.044	0.031	-10000	0	-10000	0	0
AP-1	-0.42	0.27	-10000	0	-0.82	90	90
MAPK14	0.014	0.008	-10000	0	-10000	0	0
MAPK10	-0.018	0.14	-10000	0	-0.61	22	22
MAPK11	0.014	0.008	-10000	0	-10000	0	0
KRT5	-0.27	0.24	-10000	0	-0.84	32	32
interleukin-1 receptor activity	0.031	0.031	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	-0.029	0.2	-10000	0	-0.8	27	27
CGA	-0.065	0.14	-10000	0	-0.73	6	6
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.26	0.21	0.42	230	-10000	0	230
MAPK3	0.014	0.008	-10000	0	-10000	0	0
MAPK1	0.014	0.008	-10000	0	-10000	0	0
ICAM1	-0.14	0.25	-10000	0	-0.75	36	36
NFKB1	-0.003	0.091	-10000	0	-10000	0	0
MAPK8	-0.17	0.17	-10000	0	-0.58	34	34
MAPK9	0.014	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.019	0.18	0.55	7	-0.69	4	11
BAX	0.03	0.04	-10000	0	-10000	0	0
POMC	-0.17	0.32	-10000	0	-0.93	45	45
EP300	0.073	0.093	0.32	14	-0.47	2	16
cortisol/GR alpha (dimer)/p53	0.23	0.23	0.61	62	-0.54	1	63
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.065	0.29	2	-10000	0	2
SGK1	0.12	0.14	-10000	0	-1.2	2	2
IL13	-0.22	0.19	-10000	0	-0.79	18	18
IL6	-0.19	0.36	-10000	0	-1.1	50	50
PRKACG	0.001	0.04	-10000	0	-0.82	1	1
IL5	-0.19	0.16	-10000	0	-0.74	11	11
IL2	-0.27	0.2	-10000	0	-0.8	21	21
CDK5	0.014	0.005	-10000	0	-10000	0	0
PRKACB	0.014	0	-10000	0	-10000	0	0
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.22	0.34	-10000	0	-0.78	93	93
CDK5R1/CDK5	0.003	0.033	-10000	0	-0.63	1	1
NF kappa B1 p50/RelA/PKAc	0.014	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.22	0.21	0.57	58	-10000	0	58
SMARCA4	0.015	0.007	-10000	0	-10000	0	0
chromatin remodeling	0.15	0.13	0.41	36	-10000	0	36
NF kappa B1 p50/RelA/Cbp	0.072	0.16	0.41	19	-10000	0	19
JUN (dimer)	-0.22	0.18	-10000	0	-0.66	32	32
YWHAH	0.014	0	-10000	0	-10000	0	0
VIPR1	-0.09	0.22	-10000	0	-0.71	33	33
NR3C1	0.14	0.16	0.49	39	-10000	0	39
NR4A1	-0.029	0.14	-10000	0	-0.55	16	16
TIF2/SUV420H1	-0.026	0.1	-10000	0	-0.43	26	26
MAPKKK cascade	0.028	0.18	0.54	7	-0.66	4	11
cortisol/GR alpha (dimer)/Src-1	0.23	0.22	0.59	64	-10000	0	64
PBX1	-0.092	0.23	-10000	0	-0.59	75	75
POU1F1	0.003	0.016	-10000	0	-10000	0	0
SELE	-0.22	0.41	-10000	0	-1.1	67	67
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.13	0.41	36	-10000	0	36
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.22	0.21	0.57	58	-10000	0	58
mol:cortisol	0.13	0.17	0.4	77	-10000	0	77
MMP1	-0.65	0.22	-10000	0	-0.72	375	375

×

LPA4-mediated signaling events

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
ADCY4	0.021	0	-9999	-10000	0	0
ADCY5	-0.078	0.18	-9999	-0.38	105	105
ADCY6	0.011	0.062	-9999	-0.37	11	11
ADCY7	0.021	0	-9999	-10000	0	0
ADCY1	-0.008	0.13	-9999	-0.55	22	22
ADCY2	-0.11	0.18	-9999	-0.37	140	140
ADCY3	0.021	0	-9999	-10000	0	0
ADCY8	-0.001	0.09	-9999	-0.55	11	11
PRKCE	0.012	0	-9999	-10000	0	0
ADCY9	0.02	0.027	-9999	-0.37	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.049	0.098	-9999	-0.4	5	5

×

Caspase cascade in apoptosis

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
TOP1	-0.039	0.17	-10000	0	-0.41	68	68
ACTA1	-0.14	0.23	-10000	0	-0.6	74	74
NUMA1	-0.039	0.17	-10000	0	-0.41	68	68
SPTAN1	-0.063	0.23	-10000	0	-0.55	67	67
LIMK1	-0.063	0.23	-10000	0	-0.55	67	67
BIRC3	-0.016	0.15	-10000	0	-0.82	15	15
BIRC2	-0.002	0.11	-10000	0	-0.82	8	8
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.094	0.29	-10000	0	-0.71	70	70
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.038	0.17	-10000	0	-0.41	68	68
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.061	0.22	-10000	0	-0.53	67	67
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.063	0.23	-10000	0	-0.54	70	70
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	0	0.093	-10000	0	-0.53	7	7
BID	-0.027	0.12	-10000	0	-0.36	26	26
MAP3K1	-0.012	0.073	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.003	0.023	-10000	0	-0.43	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.063	0.23	-10000	0	-0.55	67	67
CASP9	0.014	0.002	-10000	0	-10000	0	0
DNA repair	0.007	0.06	-10000	0	-0.2	7	7
neuron apoptosis	0.018	0.027	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.054	0.22	-10000	0	-0.52	67	67
APAF1	0.012	0.029	-10000	0	-0.59	1	1
CASP6	-0.002	0.1	-10000	0	-0.46	2	2
TRAF2	0.008	0.07	-10000	0	-0.82	3	3
ICAD/CAD	-0.054	0.22	-10000	0	-0.74	26	26
CASP7	0.004	0.059	0.31	11	-10000	0	11
KRT18	0.003	0.065	-10000	0	-0.47	6	6
apoptosis	-0.046	0.2	-10000	0	-0.66	27	27
DFFA	-0.063	0.23	-10000	0	-0.54	70	70
DFFB	-0.064	0.23	-10000	0	-0.55	67	67
PARP1	-0.008	0.061	0.2	7	-10000	0	7
actin filament polymerization	0.049	0.21	0.71	25	-10000	0	25
TNF	-0.025	0.17	-10000	0	-0.77	21	21
CYCS	-0.017	0.093	-10000	0	-0.28	25	25
SATB1	-0.004	0.11	-10000	0	-0.43	4	4
SLK	-0.063	0.23	-10000	0	-0.55	67	67
p15 BID/BAX	-0.017	0.11	-10000	0	-0.32	25	25
CASP2	0.035	0.068	-10000	0	-10000	0	0
JNK cascade	0.011	0.073	-10000	0	-10000	0	0
CASP3	-0.075	0.24	-10000	0	-0.57	71	71
LMNB2	0.029	0.058	-10000	0	-0.34	2	2
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	0.011	0.041	-10000	0	-0.59	2	2
Mammalian IAPs/DIABLO	-0.026	0.13	-10000	0	-0.59	19	19
negative regulation of DNA binding	0	0.092	-10000	0	-0.52	7	7
stress fiber formation	-0.061	0.22	-10000	0	-0.53	67	67
GZMB	-0.12	0.33	-10000	0	-0.79	74	74
CASP1	0.016	0.046	-10000	0	-0.6	2	2
LMNB1	0.029	0.058	-10000	0	-0.34	2	2
APP	0.018	0.027	-10000	0	-10000	0	0
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	-0.049	0.2	-10000	0	-0.46	68	68
LMNA	0.029	0.058	-10000	0	-0.34	2	2
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.028	0.072	-10000	0	-0.37	5	5
LRDD	0.012	0.04	-10000	0	-0.82	1	1
SREBF1	-0.063	0.23	-10000	0	-0.54	70	70
APAF-1/Caspase 9	-0.003	0.072	0.45	7	-10000	0	7
nuclear fragmentation during apoptosis	-0.038	0.17	-10000	0	-0.4	68	68
CFL2	-0.052	0.22	-10000	0	-0.73	25	25
GAS2	-0.11	0.25	-10000	0	-0.58	71	71
positive regulation of apoptosis	0.032	0.058	-10000	0	-0.34	2	2
PRF1	-0.044	0.21	-10000	0	-0.8	30	30

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0.04	-10000	0	-0.82	1	1
RAS family/GTP/Tiam1	-0.091	0.11	-10000	0	-0.49	5	5
NT3 (dimer)/TRKC	-0.24	0.28	-10000	0	-0.51	195	195
NT3 (dimer)/TRKB	-0.24	0.28	-10000	0	-0.69	87	87
SHC/Grb2/SOS1/GAB1/PI3K	0.038	0.024	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.042	0.2	-10000	0	-0.71	33	33
PIK3CA	0.014	0	-10000	0	-10000	0	0
DYNLT1	0.014	0	-10000	0	-10000	0	0
NTRK1	-0.055	0.23	-10000	0	-0.82	35	35
NTRK2	-0.17	0.3	-10000	0	-0.63	120	120
NTRK3	-0.14	0.26	-10000	0	-0.6	105	105
NT-4/5 (dimer)/TRKB	-0.14	0.22	-10000	0	-0.62	39	39
neuron apoptosis	0.12	0.13	0.48	20	-10000	0	20
SHC 2-3/Grb2	-0.13	0.15	-10000	0	-0.53	20	20
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.11	0.14	0.22	1	-0.42	44	45
SHC3	-0.12	0.14	-10000	0	-0.45	41	41
STAT3 (dimer)	0.013	0.055	-10000	0	-0.34	2	2
NT3 (dimer)/TRKA	-0.18	0.24	-10000	0	-0.63	52	52
RIN/GDP	-0.051	0.1	-10000	0	-0.28	3	3
GIPC1	0.014	0	-10000	0	-10000	0	0
KRAS	0.01	0.057	-10000	0	-0.82	2	2
DNAJA3	-0.078	0.12	0.25	2	-0.5	4	6
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.013	0.12	-10000	0	-0.74	11	11
MAGED1	0.007	0.07	-10000	0	-0.7	4	4
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.01	0.05	-10000	0	-0.7	2	2
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.15	0.25	-10000	0	-0.55	119	119
TRKA/NEDD4-2	-0.052	0.17	-10000	0	-0.63	35	35
ELMO1	0.012	0.029	-10000	0	-0.59	1	1
RhoG/GTP/ELMO1/DOCK1	-0.003	0.031	-10000	0	-0.36	3	3
NGF	-0.14	0.32	-10000	0	-0.8	78	78
HRAS	0.012	0.04	-10000	0	-0.82	1	1
DOCK1	0.011	0.041	-10000	0	-0.59	2	2
GAB2	0.011	0.041	-10000	0	-0.59	2	2
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.006	0.08	-10000	0	-0.82	4	4
DNM1	-0.047	0.22	-10000	0	-0.82	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.077	0.12	0.24	2	-0.48	5	7
mol:GDP	-0.076	0.14	-10000	0	-0.4	11	11
NGF (dimer)	-0.14	0.31	-10000	0	-0.8	78	78
RhoG/GDP	-0.001	0.021	-10000	0	-0.44	1	1
RIT1/GDP	-0.046	0.1	-10000	0	-0.28	3	3
TIAM1	0.006	0.065	-10000	0	-0.59	5	5
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
BDNF (dimer)/TRKB	-0.14	0.21	-10000	0	-0.58	43	43
KIDINS220/CRKL/C3G	-0.001	0.03	-10000	0	-0.63	1	1
SHC/RasGAP	-0.001	0.021	-10000	0	-0.43	1	1
FRS2 family/SHP2	-0.005	0.052	-10000	0	-0.54	4	4
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.18	0.28	-10000	0	-0.59	135	135
RAP1/GDP	-0.058	0.067	-10000	0	-0.36	1	1
KIDINS220/CRKL	0.012	0.04	-10000	0	-0.82	1	1
BDNF (dimer)	-0.042	0.2	-10000	0	-0.71	33	33
ubiquitin-dependent protein catabolic process	-0.14	0.24	-10000	0	-0.55	103	103
Schwann cell development	-0.05	0.037	-10000	0	-10000	0	0
EHD4	0.014	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.005	0.047	-10000	0	-0.49	4	4
FRS2 family/SHP2/CRK family/C3G/GAB2	0.039	0.032	-10000	0	-10000	0	0
RAP1B	0.012	0.04	-10000	0	-0.82	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.27	0.27	-10000	0	-0.63	128	128
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.073	-10000	0	-0.57	1	1
STAT3	0.013	0.055	-10000	0	-0.34	2	2
axon guidance	-0.26	0.26	-10000	0	-0.59	128	128
MAPK3	-0.11	0.24	-10000	0	-0.5	112	112
MAPK1	-0.11	0.24	-10000	0	-0.5	112	112
CDC42/GDP	-0.046	0.1	-10000	0	-0.28	3	3
NTF3	-0.18	0.28	-10000	0	-0.59	135	135
NTF4	0.01	0.05	-10000	0	-0.7	2	2
NGF (dimer)/TRKA/FAIM	-0.14	0.24	-10000	0	-0.56	103	103
PI3K	-0.003	0.036	-10000	0	-0.43	3	3
FRS3	0.014	0	-10000	0	-10000	0	0
FAIM	0.014	0	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
RASGRF1	-0.17	0.23	0.25	2	-0.54	94	96
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.2	0.27	-10000	0	-0.71	60	60
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.088	-10000	0	-10000	0	0
Rac1/GDP	-0.046	0.1	-10000	0	-0.28	3	3
NGF (dimer)/TRKA/GRIT	-0.14	0.25	-10000	0	-0.55	110	110
neuron projection morphogenesis	-0.041	0.13	-10000	0	-0.5	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.14	0.24	-10000	0	-0.56	103	103
MAP2K1	0.043	0	-10000	0	-10000	0	0
NGFR	-0.023	0.16	-10000	0	-0.72	21	21
NGF (dimer)/TRKA/GIPC/GAIP	-0.06	0.16	-10000	0	-0.56	10	10
RAS family/GTP/PI3K	0.029	0.034	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.004	0.044	-10000	0	-0.46	4	4
NRAS	0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.029	-10000	0	-0.59	1	1
MAPKKK cascade	-0.085	0.14	-10000	0	-0.48	16	16
RASA1	0.012	0.029	-10000	0	-0.59	1	1
TRKA/c-Abl	-0.052	0.17	-10000	0	-0.63	35	35
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.19	-10000	0	-0.53	43	43
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.12	0.21	-10000	0	-0.47	103	103
MATK	-0.006	0.13	-10000	0	-0.82	10	10
NEDD4L	0.014	0	-10000	0	-10000	0	0
RAS family/GDP	-0.056	0.064	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.085	0.13	0.27	2	-0.37	24	26
Rac1/GTP	-0.12	0.13	-10000	0	-0.36	65	65
FRS2 family/SHP2/CRK family	-0.005	0.049	-10000	0	-0.46	5	5

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.012	0.077	-10000	0	-10000	0	0
epithelial cell differentiation	-0.075	0.12	-10000	0	-0.58	4	4
ITCH	0.027	0.019	-10000	0	-10000	0	0
WWP1	-0.008	0.072	-10000	0	-10000	0	0
FYN	0.012	0.04	-10000	0	-0.82	1	1
EGFR	-0.017	0.15	-10000	0	-0.79	16	16
PRL	-0.003	0.08	-10000	0	-0.82	4	4
neuron projection morphogenesis	-0.035	0.17	-10000	0	-0.66	1	1
PTPRZ1	-0.003	0.1	-10000	0	-0.59	12	12
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.091	0.17	-10000	0	-0.52	26	26
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.088	0.21	-10000	0	-0.53	71	71
ADAM17	0.024	0.046	-10000	0	-0.59	2	2
ErbB4/ErbB4	-0.021	0.092	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.033	0.092	-10000	0	-0.49	5	5
NCOR1	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.095	0.19	-10000	0	-0.5	71	71
GRIN2B	-0.074	0.2	-10000	0	-0.54	27	27
ErbB4/ErbB2/betacellulin	-0.12	0.16	-10000	0	-0.63	3	3
STAT1	-0.039	0.2	-10000	0	-0.81	27	27
HBEGF	0.014	0	-10000	0	-10000	0	0
PRLR	-0.11	0.25	-10000	0	-0.6	85	85
E4ICDs/ETO2	-0.013	0.079	-10000	0	-10000	0	0
axon guidance	-0.018	0.089	-10000	0	-0.42	3	3
NEDD4	0.027	0.019	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.095	0.19	-10000	0	-0.46	87	87
CBFA2T3	0.012	0.029	-10000	0	-0.59	1	1
ErbB4/ErbB2/HBEGF	-0.016	0.066	-10000	0	-0.53	3	3
MAPK3	-0.044	0.18	-10000	0	-0.69	1	1
STAT1 (dimer)	-0.046	0.16	-10000	0	-0.57	26	26
MAPK1	-0.044	0.18	-10000	0	-0.69	1	1
JAK2	0.012	0.029	-10000	0	-0.59	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.079	0.2	-10000	0	-0.5	73	73
NRG1	-0.082	0.25	-10000	0	-0.62	74	74
NRG3	-0.005	0.09	-10000	0	-0.65	8	8
NRG2	-0.34	0.3	-10000	0	-0.59	251	251
NRG4	-0.039	0.17	-10000	0	-0.6	36	36
heart development	-0.018	0.089	-10000	0	-0.42	3	3
neural crest cell migration	-0.078	0.2	-10000	0	-0.49	73	73
ERBB2	0.026	0.064	-10000	0	-0.54	5	5
WWOX/E4ICDs	-0.012	0.077	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.078	0.14	-10000	0	-0.48	33	33
apoptosis	0.066	0.091	0.56	4	-10000	0	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.23	0.19	-10000	0	-0.48	83	83
ErbB4/ErbB2/epiregulin	-0.097	0.16	-10000	0	-0.62	7	7
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.18	-10000	0	-0.48	44	44
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.089	0.14	-10000	0	-0.66	4	4
MDM2	-0.009	0.079	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.098	0.18	-10000	0	-0.5	70	70
STAT5A	-0.009	0.083	-10000	0	-0.41	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.11	0.21	-10000	0	-0.52	81	81
DLG4	0.01	0.05	-10000	0	-0.7	2	2
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.036	0.054	-10000	0	-10000	0	0
STAT5A (dimer)	-0.079	0.13	-10000	0	-0.63	4	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.01	0.082	-10000	0	-10000	0	0
LRIG1	-0.001	0.092	-10000	0	-0.59	10	10
EREG	-0.15	0.27	-10000	0	-0.6	111	111
BTC	-0.18	0.28	-10000	0	-0.59	133	133
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.018	0.089	-10000	0	-0.42	3	3
ERBB4	-0.021	0.093	-10000	0	-10000	0	0
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.02	0.061	-10000	0	-0.4	9	9
GRB2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.044	0.11	-10000	0	-0.5	5	5
glial cell differentiation	0.036	0.053	-10000	0	-10000	0	0
WWOX	0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.15	0.24	-10000	0	-0.69	38	38

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.063	0.15	-10000	0	-0.58	24	24
FYN	-0.034	0.22	-10000	0	-0.67	34	34
LAT/GRAP2/SLP76	-0.048	0.19	-10000	0	-0.66	26	26
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.009	0.16	-10000	0	-0.46	29	29
B2M	0.013	0.005	-10000	0	-10000	0	0
IKBKG	-0.018	0.041	-10000	0	-0.18	2	2
MAP3K8	0.011	0.041	-10000	0	-0.59	2	2
mol:Ca2+	-0.04	0.041	-10000	0	-0.12	23	23
integrin-mediated signaling pathway	-0.003	0.03	-10000	0	-0.36	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.031	0.22	-10000	0	-0.68	32	32
TRPV6	-0.29	0.3	-10000	0	-0.6	207	207
CD28	-0.019	0.16	-10000	0	-0.8	17	17
SHC1	-0.037	0.22	-10000	0	-0.67	35	35
receptor internalization	-0.035	0.23	-10000	0	-0.67	37	37
PRF1	-0.05	0.27	-10000	0	-0.86	37	37
KRAS	0.01	0.057	-10000	0	-0.82	2	2
GRB2	0.014	0	-10000	0	-10000	0	0
COT/AKT1	0.002	0.13	-10000	0	-0.38	26	26
LAT	-0.044	0.24	-10000	0	-0.73	35	35
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.004	0.11	-10000	0	-0.71	10	10
CD3E	-0.002	0.11	-10000	0	-0.75	9	9
CD3G	-0.025	0.16	-10000	0	-0.7	23	23
RASGRP2	0.007	0.021	-10000	0	-0.12	4	4
RASGRP1	-0.006	0.17	-10000	0	-0.48	31	31
HLA-A	0.005	0.085	-10000	0	-0.77	5	5
RASSF5	0.009	0.051	-10000	0	-0.59	3	3
RAP1A/GTP/RAPL	-0.003	0.031	-10000	0	-0.36	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.056	-10000	0	-0.13	18	18
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.035	0.072	-10000	0	-0.27	14	14
PRKCA	-0.009	0.093	-10000	0	-0.31	16	16
GRAP2	-0.003	0.11	-10000	0	-0.7	10	10
mol:IP3	0.047	0.19	0.24	107	-0.49	19	126
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.033	0.21	-10000	0	-0.6	39	39
ORAI1	0.16	0.16	-10000	0	-10000	0	0
CSK	-0.04	0.23	-10000	0	-0.68	35	35
B7 family/CD28	-0.17	0.27	-10000	0	-0.77	50	50
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.055	0.26	-10000	0	-0.77	37	37
PTPN6	-0.044	0.23	-10000	0	-0.7	34	34
VAV1	-0.04	0.23	-10000	0	-0.68	36	36
Monovalent TCR/CD3	-0.016	0.17	-10000	0	-0.5	35	35
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.041	0.24	-10000	0	-0.72	34	34
PAG1	-0.042	0.23	-10000	0	-0.67	37	37
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.057	0.26	-10000	0	-0.76	37	37
CD80	-0.2	0.36	-10000	0	-0.82	111	111
CD86	0.011	0.04	-10000	0	-0.82	1	1
PDK1/CARD11/BCL10/MALT1	-0.043	0.088	-10000	0	-0.31	22	22
HRAS	0.012	0.04	-10000	0	-0.82	1	1
GO:0035030	-0.094	0.25	-10000	0	-0.62	50	50
CD8A	-0.048	0.21	-10000	0	-0.74	35	35
CD8B	-0.063	0.23	-10000	0	-0.73	44	44
PTPRC	-0.005	0.12	-10000	0	-0.7	11	11
PDK1/PKC theta	-0.009	0.19	-10000	0	-0.58	28	28
CSK/PAG1	-0.036	0.22	-10000	0	-0.69	31	31
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.012	0.066	-10000	0	-0.58	5	5
GRAP2/SLP76	-0.061	0.21	-10000	0	-0.69	31	31
STIM1	0.082	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.072	-10000	0	-0.18	10	10
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.041	0.25	-10000	0	-0.73	37	37
mol:DAG	-0.009	0.14	-10000	0	-0.42	24	24
RAP1A/GDP	0.013	0.024	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.018	0.16	-10000	0	-0.79	17	17
cytotoxic T cell degranulation	-0.046	0.26	-10000	0	-0.82	37	37
RAP1A/GTP	-0.002	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.019	0.18	-10000	0	-0.55	31	31
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.032	0.23	0.26	106	-0.65	21	127
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.021	0.16	-10000	0	-0.76	19	19
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.043	0.18	-10000	0	-0.63	26	26
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.012	0.04	-10000	0	-0.82	1	1
CD8 heterodimer	-0.079	0.27	-10000	0	-0.72	58	58
CARD11	-0.034	0.19	-10000	0	-0.79	25	25
PRKCB	-0.012	0.1	-10000	0	-0.37	18	18
PRKCE	-0.008	0.092	-10000	0	-0.31	16	16
PRKCQ	-0.023	0.21	-10000	0	-0.66	30	30
LCP2	0.008	0.07	-10000	0	-0.82	3	3
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.003	0.14	-10000	0	-0.39	29	29
IKK complex	0.033	0.053	-10000	0	-0.13	5	5
RAS family/GDP	-0.003	0.01	-10000	0	-0.086	3	3
MAP3K14	0.012	0.1	-10000	0	-0.31	15	15
PDPK1	-0.005	0.15	-10000	0	-0.45	26	26
TCR/CD3/MHC I/CD8/Fyn	-0.047	0.26	-10000	0	-0.78	36	36

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.003	0.016	-10000	0	-10000	0	0
AES	0.003	0.013	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	-0.008	0.07	-10000	0	-0.59	6	6
SMAD4	0.012	0.029	-10000	0	-0.59	1	1
DKK2	-0.016	0.15	-10000	0	-0.72	17	17
TLE1	0.003	0.013	-10000	0	-10000	0	0
MACF1	0.014	0.001	-10000	0	-10000	0	0
CTNNB1	0.036	0.12	0.27	5	-0.4	5	10
WIF1	-0.27	0.31	-10000	0	-0.61	188	188
beta catenin/RanBP3	-0.015	0.084	0.36	7	-10000	0	7
KREMEN2	-0.28	0.4	-10000	0	-0.82	149	149
DKK1	-0.25	0.38	-10000	0	-0.79	138	138
beta catenin/beta TrCP1	0.043	0.11	-10000	0	-10000	0	0
FZD1	0.004	0.09	-10000	0	-0.82	5	5
AXIN2	-0.001	0.17	-10000	0	-1.3	6	6
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	0.082	0.066	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.006	0.044	0.23	2	-10000	0	2
Axin1/APC/GSK3/beta catenin/Macf1	0.051	0.081	-10000	0	-10000	0	0
HNF1A	-0.011	0.11	-10000	0	-0.82	7	7
CTBP1	0.003	0.014	-10000	0	-10000	0	0
MYC	0.015	0.043	-10000	0	-0.53	1	1
RANBP3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.21	0.27	-10000	0	-0.55	158	158
NKD1	-0.021	0.16	-10000	0	-0.79	18	18
TCF4	0.003	0.014	-10000	0	-10000	0	0
TCF3	0.003	0.014	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.013	0.08	-10000	0	-0.49	11	11
Ran/GTP	0.001	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.009	0.085	0.51	6	-10000	0	6
LEF1	-0.007	0.085	-10000	0	-0.77	5	5
DVL1	0.062	0.057	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.094	0.072	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.35	0.34	-10000	0	-0.64	230	230
LRP6	0.013	0.029	-10000	0	-0.59	1	1
CSNK1A1	0.003	0.016	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.002	0.15	-10000	0	-0.83	11	11
WNT1	-0.001	0.098	-10000	0	-0.82	6	6
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
PPP2R5D	0.051	0.072	0.36	18	-10000	0	18
APC	0.028	0.082	-10000	0	-0.46	11	11
WNT1/LRP6/FZD1	0.11	0.12	0.24	188	-10000	0	188
CREBBP	0.003	0.014	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.084	0.14	-10000	0	-0.5	4	4
regulation of S phase of mitotic cell cycle	-0.043	0.12	-10000	0	-10000	0	0
GNAO1	0.006	0.075	-10000	0	-0.76	4	4
HRAS	0.011	0.04	-10000	0	-0.82	1	1
SHBG/T-DHT	-0.001	0.027	-10000	0	-0.56	1	1
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.041	0.14	-10000	0	-0.51	2	2
T-DHT/AR	-0.11	0.2	-10000	0	-0.44	108	108
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	57	57
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.029	-10000	0	-0.59	1	1
mol:GDP	-0.12	0.2	-10000	0	-0.45	108	108
cell proliferation	-0.05	0.19	-10000	0	-0.59	19	19
PIK3CA	0.014	0	-10000	0	-10000	0	0
FOS	-0.088	0.3	-10000	0	-0.83	57	57
mol:Ca2+	-0.014	0.022	-10000	0	-0.09	10	10
MAPK3	-0.044	0.16	-10000	0	-0.5	19	19
MAPK1	-0.018	0.095	-10000	0	-0.3	2	2
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
mol:IP3	0	0.002	-10000	0	-0.004	57	57
cAMP biosynthetic process	0.012	0.033	-10000	0	-0.5	1	1
GNG2	0.014	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	57	57
HRAS/GTP	-0.079	0.13	-10000	0	-0.47	5	5
actin cytoskeleton reorganization	-0.002	0.023	-10000	0	-10000	0	0
SRC	0.013	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	57	57
PI3K	-0.003	0.031	-10000	0	-0.36	3	3
apoptosis	0.043	0.18	0.43	57	-10000	0	57
T-DHT/AR/PELP1	-0.095	0.16	-10000	0	-0.37	108	108
HRAS/GDP	-0.11	0.18	-10000	0	-0.42	109	109
CREB1	-0.048	0.19	-10000	0	-0.46	57	57
RAC1-CDC42/GTP	-0.002	0.024	-10000	0	-10000	0	0
AR	-0.14	0.27	-10000	0	-0.6	108	108
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.048	0.14	-10000	0	-0.45	5	5
RAC1-CDC42/GDP	-0.1	0.17	-10000	0	-0.4	108	108
T-DHT/AR/PELP1/Src	-0.085	0.15	-10000	0	-0.38	21	21
MAP2K2	-0.041	0.14	-10000	0	-0.51	2	2
T-DHT/AR/PELP1/Src/PI3K	-0.043	0.13	-10000	0	-10000	0	0
GNAZ	-0.015	0.15	-10000	0	-0.75	16	16
SHBG	0.011	0.04	-10000	0	-0.82	1	1
Gi family/GNB1/GNG2/GDP	0.013	0.073	-10000	0	-0.45	2	2
mol:T-DHT	0	0.001	-10000	0	-0.003	38	38
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	-0.007	0.11	-10000	0	-0.62	13	13
Gi family/GTP	-0.044	0.083	-10000	0	-0.39	8	8
CDC42	0.014	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.001	0.03	-9999	-0.63	1	1
VLDLR	0.004	0.077	-9999	-0.59	7	7
CRKL	0.012	0.04	-9999	-0.82	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.012	0.04	-9999	-0.82	1	1
ITGA3	-0.019	0.16	-9999	-0.8	17	17
RELN/VLDLR/Fyn	-0.073	0.15	-9999	-0.37	84	84
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.008	0.05	-9999	-0.46	2	2
AKT1	-0.027	0.12	-9999	-0.52	4	4
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.02	0.15	-9999	-0.82	15	15
RELN/LRP8/DAB1	-0.088	0.17	-9999	-0.39	96	96
LRPAP1/LRP8	-0.013	0.09	-9999	-0.63	9	9
RELN/LRP8/DAB1/Fyn	-0.083	0.16	-9999	-0.52	27	27
DAB1/alpha3/beta1 Integrin	-0.093	0.16	-9999	-0.68	8	8
long-term memory	-0.15	0.21	-9999	-0.54	57	57
DAB1/LIS1	-0.079	0.15	-9999	-0.5	27	27
DAB1/CRLK/C3G	-0.077	0.15	-9999	-0.66	9	9
PIK3CA	0.014	0	-9999	-10000	0	0
DAB1/NCK2	-0.08	0.15	-9999	-0.51	27	27
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.12	0.28	-9999	-0.68	79	79
CDK5R1	0.012	0.04	-9999	-0.82	1	1
RELN	-0.098	0.24	-9999	-0.6	77	77
PIK3R1	0.009	0.051	-9999	-0.59	3	3
RELN/LRP8/Fyn	-0.078	0.16	-9999	-0.39	84	84
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.15	0.22	-9999	-0.55	65	65
MAPK8	0.004	0.077	-9999	-0.59	7	7
RELN/VLDLR/DAB1	-0.083	0.16	-9999	-0.37	95	95
ITGB1	0.012	0.04	-9999	-0.82	1	1
MAP1B	-0.065	0.2	-9999	-0.56	32	32
RELN/LRP8	-0.077	0.16	-9999	-0.39	83	83
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.087	0.17	-9999	-0.53	30	30
PI3K	-0.003	0.036	-9999	-0.43	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.026	0.12	-9999	-0.62	18	18
RAP1A	-0.026	0.16	-9999	-0.63	8	8
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.008	0.064	-9999	-0.74	3	3
CRLK/C3G	-0.001	0.03	-9999	-0.63	1	1
GRIN2B	-0.004	0.08	-9999	-0.82	4	4
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.01	0.1	-9999	-0.4	7	7
neuron adhesion	-0.028	0.17	-9999	-0.6	9	9
LRP8	-0.004	0.12	-9999	-0.82	9	9
GSK3B	-0.018	0.12	-9999	-0.49	4	4
RELN/VLDLR/DAB1/Fyn	-0.078	0.15	-9999	-0.52	19	19
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.039	0.13	-9999	-0.56	4	4
CDK5	0.014	0	-9999	-10000	0	0
MAPT	-0.23	0.28	-9999	-0.55	184	184
neuron migration	-0.018	0.16	-9999	-0.55	7	7
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.1	-9999	-0.41	7	7
RELN/VLDLR	-0.074	0.15	-9999	-0.58	12	12

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.012	0.029	-9999	-0.59	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.026	0.075	-9999	-0.53	2	2
IRAK/TOLLIP	0.034	0.003	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
IKBKG	0.014	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.24	0.29	-9999	-0.57	181	181
IL1A	-0.2	0.36	-9999	-0.8	108	108
IL1B	-0.046	0.2	-9999	-0.61	47	47
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.024	-9999	-10000	0	0
IL1R2	-0.11	0.25	-9999	-0.6	86	86
IL1R1	0.012	0.029	-9999	-0.59	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.023	0.078	-9999	-0.74	1	1
TOLLIP	0.014	0	-9999	-10000	0	0
TICAM2	0.014	0.001	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.071	0.019	-9999	-10000	0	0
JUN	0.032	0.074	-9999	-0.5	1	1
MAP3K7	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.051	0.14	-9999	-0.86	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.12	0.22	-9999	-0.5	104	104
PIK3R1	0.009	0.051	-9999	-0.59	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.12	0.2	-9999	-0.46	105	105
IL1 beta fragment/IL1R1/IL1RAP	-0.055	0.16	-9999	-0.5	45	45
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.025	0.078	-9999	-0.55	1	1
IRAK1	0.028	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.12	0.2	-9999	-0.43	121	121
IRAK4	0.012	0.029	-9999	-0.59	1	1
PRKCI	0.014	0	-9999	-10000	0	0
TRAF6	0.012	0.04	-9999	-0.82	1	1
PI3K	-0.003	0.036	-9999	-0.43	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.012	0.094	-9999	-0.84	1	1
CHUK	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.055	0.16	-9999	-0.5	45	45
IL1 beta/IL1R2	-0.13	0.21	-9999	-0.57	52	52
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.021	-9999	-0.43	1	1
NF kappa B1 p50/RelA	-0.045	0.13	-9999	-0.77	1	1
IRAK3	-0.001	0.11	-9999	-0.76	8	8
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.05	0.14	-9999	-0.86	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.038	0.14	-9999	-0.73	2	2
IL1 alpha/IL1R1/IL1RAP	-0.14	0.24	-9999	-0.55	104	104
RELA	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.014	0	-9999	-10000	0	0
MYD88	0.014	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.039	0.024	-9999	-0.46	1	1
IL1RAP	0.01	0.05	-9999	-0.7	2	2
UBE2N	0.014	0	-9999	-10000	0	0
IRAK/TRAF6	-0.041	0.11	-9999	-0.7	1	1
CASP1	0.012	0.029	-9999	-0.59	1	1
IL1RN/IL1R2	-0.2	0.28	-9999	-0.53	164	164
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.052	0.15	-9999	-0.47	45	45
TMEM189-UBE2V1	0.011	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.011	0.11	-9999	-0.7	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
IL1RN	-0.16	0.27	-9999	-0.59	121	121
TRAF6/TAK1/TAB1/TAB2	-0.001	0.022	-9999	-0.45	1	1
MAP2K6	0.022	0.069	-9999	-0.42	1	1

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.055	0.22	-10000	0	-0.82	34	34
GNB1/GNG2	-0.055	0.076	-10000	0	-0.21	23	23
AKT1	0	0.12	-10000	0	-0.26	1	1
EGF	-0.098	0.24	-10000	0	-0.6	77	77
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.017	0.11	-10000	0	-0.49	10	10
mol:Ca2+	-0.026	0.16	-10000	0	-0.32	38	38
LYN	0.017	0.11	-10000	0	-0.51	9	9
RhoA/GTP	-0.033	0.049	-10000	0	-0.16	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.028	0.18	-10000	0	-0.37	28	28
GNG2	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.005	0.089	-10000	0	-0.57	4	4
G beta5/gamma2	-0.071	0.1	-10000	0	-0.3	23	23
PRKCH	-0.033	0.18	-10000	0	-0.38	32	32
DNM1	-0.047	0.22	-10000	0	-0.82	31	31
TXA2/TP beta/beta Arrestin3	-0.024	0.067	-10000	0	-0.26	23	23
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.001	0.099	-10000	0	-0.75	7	7
G12 family/GTP	-0.081	0.12	-10000	0	-0.33	29	29
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.04	-10000	0	-0.82	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.012	0.12	0.37	18	-10000	0	18
mol:NADP	0.002	0.098	-10000	0	-0.82	6	6
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.022	0.16	-10000	0	-0.74	20	20
mol:IP3	-0.041	0.19	-10000	0	-0.4	41	41
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.068	0.25	-10000	0	-0.51	74	74
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.042	0.18	-10000	0	-0.5	28	28
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.014	0.12	-10000	0	-0.52	8	8
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.016	0.15	-10000	0	-0.82	15	15
PRKCB1	-0.041	0.19	-10000	0	-0.38	75	75
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	0.002	0.098	-10000	0	-0.82	6	6
TXA2/TXA2-R family	-0.068	0.25	-10000	0	-0.52	75	75
LCK	0.008	0.13	-10000	0	-0.49	14	14
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.037	0.13	-10000	0	-0.51	26	26
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.047	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.037	0.13	-10000	0	-0.51	26	26
MAPK14	-0.006	0.13	-10000	0	-0.25	5	5
TGM2/GTP	-0.054	0.22	-10000	0	-0.49	35	35
MAPK11	-0.006	0.13	-10000	0	-10000	0	0
ARHGEF1	-0.006	0.099	-10000	0	-0.22	2	2
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.04	0.2	-10000	0	-0.38	75	75
RAB11/GDP	0.014	0.002	-10000	0	-10000	0	0
ICAM1	-0.026	0.16	-10000	0	-0.35	32	32
cAMP biosynthetic process	-0.041	0.18	-10000	0	-0.39	34	34
Gq family/GTP/EBP50	-0.01	0.1	-10000	0	-0.66	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.018	0.11	-10000	0	-0.51	9	9
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.001	0.11	-10000	0	-0.34	14	14
VCAM1	-0.034	0.17	-10000	0	-0.36	53	53
TP beta/Gq family/GDP/G beta5/gamma2	0.005	0.089	-10000	0	-0.57	4	4
platelet activation	-0.011	0.17	-10000	0	-0.32	28	28
PGI2/IP	-0.022	0.12	-10000	0	-0.64	15	15
PRKACA	0.006	0.083	-10000	0	-0.36	19	19
Gq family/GDP/G beta5/gamma2	0.008	0.079	-10000	0	-0.46	4	4
TXA2/TP beta/beta Arrestin2	-0.029	0.092	-10000	0	-0.36	30	30
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.014	0.16	-10000	0	-0.54	31	31
mol:DAG	-0.049	0.21	-10000	0	-0.42	75	75
EGFR	-0.017	0.15	-10000	0	-0.79	16	16
TXA2/TP alpha	-0.062	0.24	-10000	0	-0.54	36	36
Gq family/GTP	-0.038	0.094	-10000	0	-0.24	69	69
YES1	0.018	0.11	-10000	0	-0.51	9	9
GNAI2/GTP	-0.033	0.12	-10000	0	-0.61	9	9
PGD2/DP	-0.01	0.075	-10000	0	-0.58	7	7
SLC9A3R1	0.008	0.058	-10000	0	-0.59	4	4
FYN	0.017	0.12	-10000	0	-0.52	10	10
mol:NO	0.002	0.098	-10000	0	-0.82	6	6
GNA15	0.011	0.041	-10000	0	-0.59	2	2
PGK/cGMP	-0.031	0.12	-10000	0	-0.5	26	26
RhoA/GDP	0.014	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.068	0.18	-10000	0	-0.8	15	15
NOS3	0.002	0.098	-10000	0	-0.82	6	6
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.034	0.18	-10000	0	-0.38	32	32
PRKCB	-0.038	0.19	-10000	0	-0.4	37	37
PRKCE	-0.033	0.18	-10000	0	-0.38	32	32
PRKCD	-0.038	0.19	-10000	0	-0.38	71	71
PRKCG	-0.061	0.22	-10000	0	-0.43	78	78
muscle contraction	-0.057	0.24	-10000	0	-0.48	75	75
PRKCZ	-0.028	0.18	-10000	0	-0.37	28	28
ARR3	0.002	0.004	-10000	0	-10000	0	0
TXA2/TP beta	-0.038	0.13	-10000	0	-0.51	27	27
PRKCQ	-0.037	0.18	-10000	0	-0.4	36	36
MAPKKK cascade	-0.054	0.22	-10000	0	-0.44	77	77
SELE	-0.04	0.19	-10000	0	-0.39	71	71
TP beta/GNAI2/GDP/G beta/gamma	-0.036	0.13	-10000	0	-0.69	9	9
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.083	0.22	-10000	0	-0.59	68	68
chemotaxis	-0.081	0.29	-10000	0	-0.61	74	74
GNA12	0.006	0.08	-10000	0	-0.82	4	4
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.009	0.051	-10000	0	-0.59	3	3
Rac1/GTP	0.006	0.006	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.12	0.23	-10000	0	-0.54	98	98
cell-cell adhesion	0.11	0.17	0.63	6	-10000	0	6
Ephrin B/EPHB2/RasGAP	-0.11	0.2	-10000	0	-0.48	84	84
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.01	0.06	-10000	0	-0.36	12	12
Ephrin B1/EPHB1	-0.032	0.12	-10000	0	-0.49	28	28
HRAS/GDP	-0.056	0.11	-10000	0	-0.57	5	5
Ephrin B/EPHB1/GRB7	-0.05	0.14	-10000	0	-0.49	25	25
Endophilin/SYNJ1	-0.072	0.2	-10000	0	-0.44	84	84
KRAS	0.01	0.057	-10000	0	-0.82	2	2
Ephrin B/EPHB1/Src	-0.045	0.13	-10000	0	-0.49	21	21
endothelial cell migration	-0.003	0.028	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
GRB7	0.004	0.085	-10000	0	-0.77	5	5
PAK1	-0.088	0.22	-10000	0	-0.68	13	13
HRAS	0.012	0.04	-10000	0	-0.82	1	1
RRAS	-0.073	0.2	-10000	0	-0.45	84	84
DNM1	-0.047	0.22	-10000	0	-0.82	31	31
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.14	-10000	0	-0.47	21	21
lamellipodium assembly	-0.11	0.17	-10000	0	-0.63	6	6
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.009	0.095	-10000	0	-0.47	3	3
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
EPHB2	-0.15	0.33	-10000	0	-0.82	84	84
EPHB3	-0.003	0.1	-10000	0	-0.59	12	12
EPHB1	-0.036	0.19	-10000	0	-0.74	28	28
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.051	0.11	-10000	0	-0.55	5	5
Ephrin B/EPHB2	-0.11	0.2	-10000	0	-0.48	84	84
Ephrin B/EPHB3	-0.027	0.089	-10000	0	-0.54	2	2
JNK cascade	-0.084	0.22	-10000	0	-0.46	102	102
Ephrin B/EPHB1	-0.046	0.13	-10000	0	-0.5	21	21
RAP1/GDP	-0.043	0.097	-10000	0	-0.49	4	4
EFNB2	0.012	0.029	-10000	0	-0.59	1	1
EFNB3	-0.023	0.14	-10000	0	-0.6	25	25
EFNB1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.13	0.22	-10000	0	-0.51	102	102
RAP1B	0.012	0.04	-10000	0	-0.82	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.11	0.17	-10000	0	-0.7	6	6
Rap1/GTP	-0.11	0.17	-10000	0	-0.65	6	6
axon guidance	-0.12	0.23	-10000	0	-0.54	98	98
MAPK3	0.025	0.086	-10000	0	-0.41	3	3
MAPK1	0.025	0.086	-10000	0	-0.41	3	3
Rac1/GDP	-0.009	0.12	-10000	0	-0.52	4	4
actin cytoskeleton reorganization	-0.087	0.13	-10000	0	-0.54	5	5
CDC42/GDP	-0.009	0.12	-10000	0	-0.52	4	4
PI3K	-0.003	0.029	-10000	0	-10000	0	0
EFNA5	-0.013	0.12	-10000	0	-0.59	19	19
Ephrin B2/EPHB4	-0.001	0.018	-10000	0	-0.36	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.036	0.14	-10000	0	-0.57	3	3
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.11	0.17	-10000	0	-0.64	7	7
PTK2	0.026	0.045	-10000	0	-10000	0	0
MAP4K4	-0.085	0.22	-10000	0	-0.46	102	102
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.029	0.16	-10000	0	-0.59	30	30
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.041	0.17	-10000	0	-0.48	11	11
MAP2K1	0.018	0.09	-10000	0	-0.44	3	3
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.13	0.22	-10000	0	-0.5	102	102
cell migration	0.021	0.1	-10000	0	-0.5	3	3
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	-0.073	0.2	-10000	0	-0.45	84	84
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.26	0.24	-10000	0	-0.67	78	78
HRAS/GTP	-0.12	0.18	-10000	0	-0.72	7	7
Ephrin B1/EPHB1-2	-0.13	0.22	-10000	0	-0.51	102	102
cell adhesion mediated by integrin	0.014	0.081	0.45	2	-10000	0	2
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.12	0.2	-10000	0	-0.78	6	6
RAC1-CDC42/GTP	-0.11	0.17	-10000	0	-0.69	6	6
RASA1	0.012	0.029	-10000	0	-0.59	1	1
RAC1-CDC42/GDP	-0.042	0.096	-10000	0	-0.49	4	4
ruffle organization	-0.06	0.2	-10000	0	-0.74	4	4
NCK1	0.014	0	-10000	0	-10000	0	0
receptor internalization	-0.094	0.24	-10000	0	-0.84	17	17
Ephrin B/EPHB2/KALRN	-0.13	0.21	-10000	0	-0.49	89	89
ROCK1	0.017	0.058	-10000	0	-10000	0	0
RAS family/GDP	-0.084	0.13	-10000	0	-0.54	5	5
Rac1/GTP	-0.11	0.18	-10000	0	-0.7	6	6
Ephrin B/EPHB1/Src/Paxillin	0.003	0.1	-10000	0	-0.52	3	3

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.026	0.14	-10000	0	-0.43	20	20
IKBKB	-0.007	0.078	-10000	0	-0.27	6	6
AKT1	-0.025	0.12	-10000	0	-0.28	35	35
IKBKG	-0.006	0.082	-10000	0	-0.29	6	6
CALM1	-0.043	0.12	-10000	0	-0.41	23	23
PIK3CA	0.014	0	-10000	0	-10000	0	0
MAP3K1	-0.052	0.2	-10000	0	-0.48	58	58
MAP3K7	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.053	0.12	-10000	0	-0.44	24	24
DOK1	0.014	0	-10000	0	-10000	0	0
AP-1	-0.021	0.097	-10000	0	-0.26	11	11
LYN	0.012	0.029	-10000	0	-0.59	1	1
BLNK	-0.048	0.18	-10000	0	-0.59	43	43
SHC1	0.014	0	-10000	0	-10000	0	0
BCR complex	-0.13	0.27	-10000	0	-0.63	88	88
CD22	-0.12	0.26	-10000	0	-0.82	41	41
CAMK2G	-0.032	0.11	-10000	0	-0.38	23	23
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	0.011	0.041	-10000	0	-0.59	2	2
SHC/GRB2/SOS1	-0.11	0.19	-10000	0	-0.65	23	23
GO:0007205	-0.054	0.12	-10000	0	-0.44	24	24
SYK	0.011	0.041	-10000	0	-0.59	2	2
ELK1	-0.045	0.12	-10000	0	-0.42	24	24
NFATC1	-0.064	0.19	-10000	0	-0.47	58	58
B-cell antigen/BCR complex	-0.13	0.27	-10000	0	-0.63	88	88
PAG1/CSK	-0.003	0.043	-10000	0	-0.63	2	2
NFKBIB	0.008	0.03	-10000	0	-10000	0	0
HRAS	-0.047	0.13	-10000	0	-0.45	23	23
NFKBIA	0.009	0.029	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.015	0.025	-10000	0	-10000	0	0
RasGAP/Csk	-0.1	0.21	-10000	0	-0.55	64	64
mol:GDP	-0.052	0.12	-10000	0	-0.42	24	24
PTEN	0.014	0	-10000	0	-10000	0	0
CD79B	-0.012	0.14	-10000	0	-0.75	14	14
NF-kappa-B/RelA/I kappa B alpha	0.015	0.024	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.09	0.23	-10000	0	-0.55	67	67
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
mol:IP3	-0.063	0.12	-10000	0	-0.45	24	24
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.073	0.16	-10000	0	-0.44	42	42
CHUK	-0.006	0.082	-10000	0	-0.29	6	6
IBTK	0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.067	0.13	-10000	0	-0.56	12	12
PTPN6	-0.11	0.24	-10000	0	-0.77	40	40
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	0.008	0.039	-10000	0	-0.13	26	26
VAV2	-0.15	0.26	-10000	0	-0.74	59	59
ubiquitin-dependent protein catabolic process	0.013	0.029	-10000	0	-10000	0	0
BTK	-0.003	0.03	-10000	0	-10000	0	0
CD19	-0.15	0.29	-10000	0	-0.77	67	67
MAP4K1	-0.006	0.12	-10000	0	-0.76	11	11
CD72	-0.066	0.24	-10000	0	-0.81	41	41
PAG1	0.01	0.057	-10000	0	-0.82	2	2
MAPK14	-0.034	0.17	-10000	0	-0.52	22	22
SH3BP5	0.011	0.041	-10000	0	-0.59	2	2
PIK3AP1	-0.058	0.15	-10000	0	-0.47	36	36
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.081	0.2	-10000	0	-0.59	34	34
RAF1	-0.036	0.13	-10000	0	-0.42	23	23
RasGAP/p62DOK/SHIP	-0.097	0.2	-10000	0	-0.77	17	17
CD79A	-0.14	0.31	-10000	0	-0.74	87	87
re-entry into mitotic cell cycle	-0.022	0.097	-10000	0	-0.26	11	11
RASA1	0.012	0.029	-10000	0	-0.59	1	1
MAPK3	-0.015	0.11	-10000	0	-0.44	2	2
MAPK1	-0.015	0.11	-10000	0	-0.44	2	2
CD72/SHP1	-0.098	0.3	-10000	0	-0.88	39	39
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.039	0.18	-10000	0	-0.53	23	23
actin cytoskeleton organization	-0.086	0.24	-10000	0	-0.61	58	58
NF-kappa-B/RelA	0.035	0.047	-10000	0	-10000	0	0
Calcineurin	-0.045	0.086	-10000	0	-0.47	2	2
PI3K	-0.12	0.22	-10000	0	-0.61	60	60
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.066	0.13	0.24	2	-0.47	25	27
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.055	0.22	-10000	0	-0.77	26	26
DAPP1	-0.085	0.2	-10000	0	-0.77	24	24
cytokine secretion	-0.058	0.18	-10000	0	-0.43	58	58
mol:DAG	-0.063	0.12	-10000	0	-0.45	24	24
PLCG2	0.012	0.029	-10000	0	-0.59	1	1
MAP2K1	-0.026	0.12	-10000	0	-0.4	12	12
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.24	-10000	0	-0.64	64	64
mol:PI-3-4-5-P3	-0.086	0.15	-10000	0	-0.41	57	57
ETS1	-0.025	0.11	-10000	0	-0.41	7	7
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.22	-10000	0	-0.55	71	71
B-cell antigen/BCR complex/LYN	-0.087	0.19	-10000	0	-0.76	19	19
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.012	0.04	-10000	0	-0.82	1	1
RAC1	-0.095	0.26	-10000	0	-0.66	58	58
B-cell antigen/BCR complex/LYN/SYK	-0.12	0.26	-10000	0	-0.86	36	36
CARD11	-0.069	0.17	-10000	0	-0.5	43	43
FCGR2B	0.005	0.071	-10000	0	-0.59	6	6
PPP3CA	0.014	0	-10000	0	-10000	0	0
BCL10	0.014	0	-10000	0	-10000	0	0
IKK complex	0.008	0.039	-10000	0	-10000	0	0
PTPRC	-0.005	0.11	-10000	0	-0.69	11	11
PDPK1	-0.025	0.12	-10000	0	-0.29	32	32
PPP3CB	0.014	0	-10000	0	-10000	0	0
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.009	0.04	-10000	0	-0.14	25	25

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.054	0.17	0.6	37	-10000	0	37
KIRREL	-0.012	0.12	-10000	0	-0.67	13	13
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.054	0.17	-10000	0	-0.6	37	37
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.05	0.16	-10000	0	-0.54	34	34
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.003	0.11	-10000	0	-0.57	6	6
FYN	-0.029	0.15	-10000	0	-0.49	35	35
mol:Ca2+	-0.049	0.16	-10000	0	-0.54	34	34
mol:DAG	-0.05	0.16	-10000	0	-0.54	34	34
NPHS2	-0.022	0.13	-10000	0	-0.85	10	10
mol:IP3	-0.05	0.16	-10000	0	-0.54	34	34
regulation of endocytosis	-0.043	0.14	-10000	0	-0.48	28	28
Nephrin/NEPH1/podocin/Cholesterol	-0.051	0.16	-10000	0	-0.55	34	34
establishment of cell polarity	-0.054	0.17	-10000	0	-0.6	37	37
Nephrin/NEPH1/podocin/NCK1-2	-0.045	0.15	-10000	0	-0.5	34	34
Nephrin/NEPH1/beta Arrestin2	-0.02	0.15	-10000	0	-0.49	28	28
NPHS1	-0.044	0.2	-10000	0	-0.83	25	25
Nephrin/NEPH1/podocin	-0.047	0.15	-10000	0	-0.5	35	35
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.014	0	-10000	0	-10000	0	0
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.05	0.16	-10000	0	-0.54	34	34
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.05	0.16	-10000	0	-0.54	34	34
GRB2	0.014	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.056	0.2	-10000	0	-0.52	57	57
cytoskeleton organization	-0.005	0.14	-10000	0	-0.76	6	6
Nephrin/NEPH1	-0.04	0.13	-10000	0	-0.45	37	37
Nephrin/NEPH1/ZO-1	-0.044	0.14	-10000	0	-0.54	29	29

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.077	-9999	-0.6	7	7
alphaV beta3 Integrin	-0.041	0.14	-9999	-0.5	35	35
PTK2	-0.009	0.16	-9999	-0.61	9	9
IGF1R	0.012	0.04	-9999	-0.82	1	1
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.041	0.11	-9999	-0.41	30	30
VEGFA	0.004	0.09	-9999	-0.82	5	5
ILK	-0.041	0.11	-9999	-0.41	30	30
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	-0.004	0.12	-9999	-0.5	4	4
PTK2B	0.009	0.13	-9999	-0.49	23	23
alphaV/beta3 Integrin/JAM-A	-0.067	0.17	-9999	-0.51	49	49
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.031	0.12	-9999	-0.55	20	20
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.051	0.12	-9999	-0.51	7	7
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.013	0.091	-9999	-0.43	5	5
alphaV/beta3 Integrin/Syndecan-1	-0.027	0.12	-9999	-0.55	17	17
PI4KA	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.28	0.26	-9999	-0.79	42	42
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.3	0.29	-9999	-0.56	221	221
RPS6KB1	-0.23	0.26	-9999	-0.72	42	42
TLN1	0.01	0.057	-9999	-0.82	2	2
MAPK3	-0.12	0.16	-9999	-0.61	29	29
GPR124	0.006	0.08	-9999	-0.82	4	4
MAPK1	-0.12	0.16	-9999	-0.61	29	29
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
alphaV/beta3 Integrin/Tumstatin	-0.087	0.2	-9999	-0.58	52	52
cell adhesion	-0.026	0.1	-9999	-0.46	17	17
ANGPTL3	-0.001	0.069	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.066	-9999	-0.54	6	6
IGF-1R heterotetramer	0.012	0.04	-9999	-0.82	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.012	0.029	-9999	-0.59	1	1
ITGB3	-0.022	0.16	-9999	-0.74	20	20
IGF1	-0.077	0.22	-9999	-0.61	62	62
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.032	0.13	-9999	-0.57	20	20
apoptosis	0.006	0.075	-9999	-0.76	4	4
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.027	0.12	-9999	-0.55	17	17
VCL	0.012	0.029	-9999	-0.59	1	1
alphaV/beta3 Integrin/Del1	-0.093	0.21	-9999	-0.58	55	55
CSF1	0.006	0.065	-9999	-0.59	5	5
PIK3C2A	-0.041	0.11	-9999	-0.41	30	30
PI4 Kinase/Pyk2	-0.062	0.15	-9999	-0.8	6	6
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.032	0.12	-9999	-0.52	23	23
FAK1/Vinculin	0.002	0.13	-9999	-0.5	6	6
alphaV beta3/Integrin/ppsTEM5	-0.032	0.13	-9999	-0.57	20	20
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.045	0.21	-9999	-0.82	30	30
BCAR1	0.014	0	-9999	-10000	0	0
FGF2	-0.01	0.12	-9999	-0.65	15	15
F11R	0.007	0.095	-9999	-0.48	15	15
alphaV/beta3 Integrin/Lactadherin	-0.027	0.12	-9999	-0.55	17	17
alphaV/beta3 Integrin/TGFBR2	-0.028	0.12	-9999	-0.49	24	24
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.008	0.055	-9999	-0.49	3	3
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.027	0.11	-9999	-0.51	19	19
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.39	0.42	-9999	-0.82	207	207
alphaV/beta3 Integrin/Pyk2	0.009	0.13	-9999	-0.49	23	23
SDC1	0.014	0	-9999	-10000	0	0
VAV3	0.012	0.1	-9999	-0.51	5	5
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.011	0.041	-9999	-0.59	2	2
FAK1/Paxillin	0.002	0.13	-9999	-0.48	7	7
cell migration	0.012	0.12	-9999	-0.45	5	5
ITGAV	0.006	0.075	-9999	-0.76	4	4
PI3K	-0.062	0.16	-9999	-0.74	8	8
SPP1	-0.4	0.42	-9999	-0.82	214	214
KDR	0.01	0.05	-9999	-0.7	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.006	0.075	-9999	-0.76	4	4
COL4A3	-0.081	0.26	-9999	-0.76	52	52
angiogenesis	-0.088	0.18	-9999	-0.66	20	20
Rac1/GTP	-0.024	0.083	-9999	-0.55	2	2
EDIL3	-0.091	0.26	-9999	-0.74	59	59
cell proliferation	-0.028	0.12	-9999	-0.49	24	24

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.005	0.042	-10000	0	-0.58	2	2
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.041	0.17	-10000	0	-0.54	19	19
AKT1	0.001	0.032	-10000	0	-10000	0	0
GSC	-0.019	0.19	-10000	0	-0.65	32	32
NKX2-5	-0.17	0.33	-10000	0	-0.75	102	102
muscle cell differentiation	0.13	0.21	0.67	35	-10000	0	35
SMAD2-3/SMAD4/SP1	-0.05	0.1	-10000	0	-10000	0	0
SMAD4	0.001	0.046	-10000	0	-0.56	1	1
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.015	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.006	0.08	-10000	0	-0.54	8	8
SMAD3/SMAD4/VDR	0.005	0.043	-10000	0	-10000	0	0
MYC	0.027	0.033	-10000	0	-10000	0	0
CDKN2B	-0.24	0.57	-10000	0	-1.4	85	85
AP1	-0.006	0.11	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.056	0.041	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.056	0.16	-10000	0	-0.57	11	11
SP3	0.016	0.001	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.092	0.27	-10000	0	-0.81	53	53
SMAD3/SMAD4/GR	0.034	0.068	-10000	0	-10000	0	0
GATA3	-0.012	0.14	-10000	0	-0.78	14	14
SKI/SIN3/HDAC complex/NCoR1	0.056	0.024	-10000	0	-10000	0	0
MEF2C/TIF2	-0.15	0.27	-10000	0	-0.78	38	38
endothelial cell migration	0.37	0.33	0.65	249	-10000	0	249
MAX	0.035	0.02	-10000	0	-10000	0	0
RBBP7	0.015	0.002	-10000	0	-10000	0	0
RBBP4	0.012	0.042	-10000	0	-0.59	2	2
RUNX2	0.011	0.041	-10000	0	-0.59	2	2
RUNX3	0.004	0.09	-10000	0	-0.82	5	5
RUNX1	0.014	0	-10000	0	-10000	0	0
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.035	0.02	-10000	0	-10000	0	0
VDR	0.012	0.029	-10000	0	-0.59	1	1
CDKN1A	0.011	0.094	-10000	0	-10000	0	0
KAT2B	-0.019	0.13	-10000	0	-0.59	20	20
SMAD2/SMAD2/SMAD4/FOXH1	-0.065	0.19	-10000	0	-0.55	53	53
DCP1A	0.014	0	-10000	0	-10000	0	0
SKI	0.015	0.002	-10000	0	-10000	0	0
SERPINE1	-0.37	0.33	-10000	0	-0.65	249	249
SMAD3/SMAD4/ATF2	0.01	0.047	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.002	0.078	-10000	0	-0.49	5	5
SAP30	0.015	0.002	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.002	0.038	-10000	0	-0.36	1	1
JUN	0.013	0.12	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.013	0.13	-10000	0	-0.6	14	14
TFE3	0	0.018	-10000	0	-10000	0	0
COL1A2	-0.29	0.35	-10000	0	-0.69	184	184
mesenchymal cell differentiation	-0.008	0.054	0.4	1	-10000	0	1
DLX1	-0.36	0.41	-10000	0	-0.82	193	193
TCF3	0.014	0	-10000	0	-10000	0	0
FOS	-0.062	0.21	-10000	0	-0.58	57	57
SMAD3/SMAD4/Max	0.034	0.068	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.001	0.026	-10000	0	-10000	0	0
ZBTB17	0.024	0.026	-10000	0	-10000	0	0
LAMC1	0.008	0.044	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.008	0.057	-10000	0	-0.66	1	1
IRF7	-0.018	0.16	-10000	0	-0.8	16	16
ESR1	-0.014	0.18	-10000	0	-0.73	25	25
HNF4A	-0.068	0.24	-10000	0	-0.82	40	40
MEF2C	-0.13	0.27	-10000	0	-0.68	41	41
SMAD2-3/SMAD4	-0.003	0.061	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.004	0.031	-10000	0	-0.36	1	1
IGHV3OR16-13	-0.001	0.012	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.012	0.04	-10000	0	-0.82	1	1
CREBBP	0.007	0.01	-10000	0	-10000	0	0
SKIL	0.014	0	-10000	0	-10000	0	0
HDAC1	0.015	0.002	-10000	0	-10000	0	0
HDAC2	0.015	0.002	-10000	0	-10000	0	0
SNIP1	0.016	0.004	-10000	0	-10000	0	0
GCN5L2	-0.009	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.005	0.045	-10000	0	-10000	0	0
MSG1/HSC70	0.006	0.089	-10000	0	-0.63	8	8
SMAD2	0.001	0.037	-10000	0	-10000	0	0
SMAD3	0.006	0.044	-10000	0	-0.54	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.021	0.05	-10000	0	-0.46	1	1
SMAD2/SMAD2/SMAD4	-0.024	0.081	-10000	0	-0.36	21	21
NCOR1	0.015	0.002	-10000	0	-10000	0	0
NCOA2	-0.023	0.14	-10000	0	-0.59	26	26
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.07	0.16	-10000	0	-0.44	68	68
SMAD2-3/SMAD4/SP1/MIZ-1	-0.04	0.097	-10000	0	-10000	0	0
IFNB1	0.003	0.15	-10000	0	-0.64	17	17
SMAD3/SMAD4/MEF2C	-0.13	0.26	-10000	0	-0.72	30	30
CITED1	-0.002	0.11	-10000	0	-0.82	8	8
SMAD2-3/SMAD4/ARC105	0.005	0.062	-10000	0	-0.55	1	1
RBL1	0.012	0.029	-10000	0	-0.59	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.06	0.22	-10000	0	-0.49	82	82
RUNX1-3/PEBPB2	-0.006	0.058	-10000	0	-0.54	5	5
SMAD7	-0.028	0.12	-10000	0	-10000	0	0
MYC/MIZ-1	0.032	0.065	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.12	0.15	0.36	4	-0.4	4	8
IL10	0.012	0.15	-10000	0	-0.64	17	17
PIASy/HDAC complex	0.023	0.012	-10000	0	-10000	0	0
PIAS3	0.007	0.008	-10000	0	-10000	0	0
CDK2	0.007	0.01	-10000	0	-10000	0	0
IL5	0.01	0.13	-10000	0	-0.62	9	9
CDK4	0.007	0.011	-10000	0	-10000	0	0
PIAS4	0.023	0.012	-10000	0	-10000	0	0
ATF3	0.001	0.091	-10000	0	-0.65	8	8
SMAD3/SMAD4/SP1	-0.062	0.089	-10000	0	-10000	0	0
FOXG1	-0.098	0.26	-10000	0	-0.72	60	60
FOXO3	0.009	0.043	-10000	0	-10000	0	0
FOXO1	0.009	0.043	-10000	0	-10000	0	0
FOXO4	0.007	0.052	-10000	0	-0.42	2	2
heart looping	-0.13	0.26	-10000	0	-0.66	42	42
CEBPB	0.008	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.25	0.29	-10000	0	-0.57	192	192
MYOD1	-0.091	0.22	-10000	0	-0.6	68	68
SMAD3/SMAD4/HNF4	-0.046	0.17	-10000	0	-0.56	40	40
SMAD3/SMAD4/GATA3	-0.01	0.12	-10000	0	-0.58	12	12
SnoN/SIN3/HDAC complex/NCoR1	0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.012	0.068	-10000	0	-0.48	3	3
SMAD3/SMAD4/SP1-3	-0.037	0.08	-10000	0	-10000	0	0
MED15	0.012	0.04	-10000	0	-0.82	1	1
SP1	-0.043	0.075	-10000	0	-10000	0	0
SIN3B	0.015	0.002	-10000	0	-10000	0	0
SIN3A	0.015	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.16	0.27	-10000	0	-0.56	115	115
ITGB5	0	0.093	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.085	0.18	-10000	0	-0.47	25	25
AR	-0.14	0.27	-10000	0	-0.6	108	108
negative regulation of cell growth	0.022	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.057	0.16	-10000	0	-0.5	14	14
E2F5	0.009	0.051	-10000	0	-0.59	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.06	0.16	-10000	0	-0.5	35	35
SMAD2-3/SMAD4/FOXO1-3a-4	-0.03	0.15	-10000	0	-10000	0	0
TFDP1	0.012	0.04	-10000	0	-0.82	1	1
SMAD3/SMAD4/AP1	0	0.12	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.008	0.054	-10000	0	-0.4	1	1
TGIF2	0.012	0.04	-10000	0	-0.82	1	1
TGIF1	0.014	0	-10000	0	-10000	0	0
ATF2	0.014	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.028	0.042	-9999	-10000	0	0
SNTA1	0.014	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.024	0.063	-9999	-0.54	3	3
MAPK12	-0.009	0.14	-9999	-0.56	20	20
CCND1	-0.001	0.089	-9999	-0.35	14	14
p38 gamma/SNTA1	-0.002	0.14	-9999	-0.52	20	20
MAP2K3	0.012	0.029	-9999	-0.59	1	1
PKN1	0.012	0.04	-9999	-0.82	1	1
G2/M transition checkpoint	-0.009	0.14	-9999	-0.56	20	20
MAP2K6	0.007	0.086	-9999	-0.37	20	20
MAPT	-0.14	0.18	-9999	-0.33	184	184
MAPK13	0.019	0.049	-9999	-0.43	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.017	0.026	-9999	-0.36	2	2

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.006	0.13	-9999	-0.82	10	10
Syndecan-3/Src/Cortactin	-0.11	0.15	-9999	-0.57	11	11
Syndecan-3/Neurocan	-0.017	0.086	-9999	-0.45	16	16
POMC	-0.076	0.25	-9999	-0.78	48	48
EGFR	-0.017	0.15	-9999	-0.79	16	16
Syndecan-3/EGFR	-0.018	0.086	-9999	-0.45	15	15
AGRP	0.003	0.04	-9999	-0.82	1	1
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.012	0.04	-9999	-0.82	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.02	0.15	-9999	-0.82	15	15
long-term memory	-0.012	0.07	-9999	-0.43	11	11
Syndecan-3/IL8	-0.097	0.19	-9999	-0.46	88	88
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	-0.015	0.095	-9999	-0.63	10	10
FYN	0.012	0.04	-9999	-0.82	1	1
limb bud formation	-0.001	0.019	-9999	-0.37	1	1
MC4R	0.002	0.057	-9999	-0.82	2	2
SRC	0.014	0	-9999	-10000	0	0
PTN	-0.22	0.3	-9999	-0.59	162	162
FGFR/FGF/Syndecan-3	-0.001	0.019	-9999	-0.38	1	1
neuron projection morphogenesis	-0.12	0.16	-9999	-0.68	9	9
Syndecan-3/AgRP	-0.002	0.028	-9999	-0.41	2	2
Syndecan-3/AgRP/MC4R	-0.004	0.04	-9999	-0.44	3	3
Fyn/Cortactin	-0.016	0.1	-9999	-0.63	11	11
SDC3	-0.001	0.019	-9999	-0.38	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.095	0.18	-9999	-0.45	88	88
IL8	-0.16	0.34	-9999	-0.81	89	89
Syndecan-3/Fyn/Cortactin	-0.012	0.071	-9999	-0.44	11	11
Syndecan-3/CASK	-0.001	0.018	-9999	-0.36	1	1
alpha-MSH/MC4R	-0.07	0.2	-9999	-0.6	49	49
Gamma Secretase	-0.001	0.022	-9999	-0.46	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.014	0.053	-10000	0	-0.8	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.05	0.17	0.63	17	-10000	0	17
IL27/IL27R/JAK1	-0.094	0.19	-10000	0	-0.78	15	15
TBX21	-0.095	0.25	-10000	0	-0.68	35	35
IL12B	-0.066	0.24	-10000	0	-0.82	39	39
IL12A	-0.006	0.089	-10000	0	-0.46	15	15
IL6ST	-0.048	0.18	-10000	0	-0.6	41	41
IL27RA/JAK1	-0.008	0.11	-10000	0	-0.58	14	14
IL27	-0.027	0.17	-10000	0	-0.83	18	18
TYK2	0.011	0.042	-10000	0	-0.83	1	1
T-helper cell lineage commitment	-0.022	0.13	-10000	0	-0.64	7	7
T-helper 2 cell differentiation	0.05	0.17	0.63	17	-10000	0	17
T cell proliferation during immune response	0.05	0.17	0.63	17	-10000	0	17
MAPKKK cascade	-0.05	0.17	-10000	0	-0.63	17	17
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.014	0	-10000	0	-10000	0	0
STAT1	-0.04	0.2	-10000	0	-0.82	27	27
IL12RB1	-0.063	0.24	-10000	0	-0.81	39	39
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.14	0.32	-10000	0	-0.69	86	86
IL27/IL27R/JAK2/TYK2	-0.051	0.18	-10000	0	-0.64	17	17
positive regulation of T cell mediated cytotoxicity	-0.05	0.17	-10000	0	-0.63	17	17
STAT1 (dimer)	-0.17	0.29	0.52	1	-0.89	38	39
JAK2	0.011	0.03	-10000	0	-0.6	1	1
JAK1	0.013	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.041	0.17	-10000	0	-0.7	10	10
T cell proliferation	-0.075	0.2	-10000	0	-0.63	24	24
IL12/IL12R/TYK2/JAK2	-0.063	0.19	-10000	0	-0.59	29	29
IL17A	-0.023	0.12	-10000	0	-0.64	7	7
mast cell activation	0.05	0.17	0.63	17	-10000	0	17
IFNG	-0.017	0.05	-10000	0	-0.11	89	89
T cell differentiation	-0.006	0.009	-10000	0	-0.025	40	40
STAT3 (dimer)	-0.041	0.17	-10000	0	-0.6	17	17
STAT5A (dimer)	-0.041	0.17	-10000	0	-0.6	17	17
STAT4 (dimer)	-0.05	0.18	-10000	0	-0.7	13	13
STAT4	-0.002	0.11	-10000	0	-0.79	8	8
T cell activation	-0.006	0.019	0.093	14	-10000	0	14
IL27R/JAK2/TYK2	-0.044	0.16	-10000	0	-0.66	11	11
GATA3	0.002	0.14	-10000	0	-0.69	14	14
IL18	-0.004	0.083	-10000	0	-0.44	15	15
positive regulation of mast cell cytokine production	-0.04	0.16	-10000	0	-0.59	17	17
IL27/EBI3	-0.029	0.16	-10000	0	-0.62	27	27
IL27RA	-0.017	0.12	-10000	0	-0.64	14	14
IL6	-0.051	0.2	-10000	0	-0.63	43	43
STAT5A	0.014	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.015	0.066	-10000	0	-10000	0	0
IL1B	-0.057	0.2	-10000	0	-0.62	46	46
EBI3	-0.005	0.11	-10000	0	-0.73	9	9
TNF	-0.018	0.13	-10000	0	-0.6	21	21

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.16	0.28	-9999	-0.61	115	115
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.012	0.04	-9999	-0.82	1	1
TCEB1	0.012	0.04	-9999	-0.82	1	1
HIF1A/p53	0.024	0.041	-9999	-10000	0	0
HIF1A	0.02	0.031	-9999	-10000	0	0
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.038	-9999	-0.46	3	3
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.35	0.4	-9999	-0.77	194	194
ARNT/IPAS	-0.12	0.2	-9999	-0.44	115	115
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.027	0.03	-9999	-10000	0	0
CUL2	0.012	0.04	-9999	-0.82	1	1
OS9	0.014	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.003	0.037	-9999	-0.54	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.027	0.03	-9999	-10000	0	0
PHD1-3/OS9	-0.027	0.11	-9999	-0.49	21	21
HIF1A/RACK1/Elongin B/Elongin C	-0.006	0.035	-9999	-0.45	2	2
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.027	0.03	-9999	-10000	0	0
EGLN3	-0.033	0.19	-9999	-0.78	25	25
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	0.008	0.058	-9999	-0.59	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.037	0.024	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.014	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.17	0.22	-9999	-0.44	159	159

×

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	-0.047	0.1	-9999	-0.82	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.052	-9999	-10000	0	0
AP1	-0.078	0.13	-9999	-0.56	9	9
mol:PIP3	-0.053	0.11	-9999	-0.52	5	5
AKT1	0.022	0.091	-9999	-0.53	1	1
PTK2B	-0.004	0.078	-9999	-0.29	4	4
RHOA	0.007	0.062	-9999	-0.33	1	1
PIK3CB	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	0.009	0.072	-9999	-0.43	3	3
MAGI3	0.011	0.041	-9999	-0.59	2	2
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.022	0.11	-9999	-0.6	3	3
HRAS/GDP	-0.001	0.031	-9999	-0.64	1	1
positive regulation of microtubule depolymerization	-0.12	0.16	-9999	-0.43	27	27
NF kappa B1 p50/RelA	-0.034	0.088	-9999	-0.55	3	3
endothelial cell migration	-0.1	0.29	-9999	-0.76	69	69
ADCY4	-0.011	0.12	-9999	-0.46	13	13
ADCY5	-0.059	0.15	-9999	-0.54	15	15
ADCY6	-0.016	0.13	-9999	-0.49	14	14
ADCY7	-0.011	0.12	-9999	-0.46	13	13
ADCY1	-0.019	0.13	-9999	-0.45	14	14
ADCY2	-0.077	0.14	-9999	-0.5	18	18
ADCY3	-0.011	0.12	-9999	-0.46	13	13
ADCY8	-0.018	0.13	-9999	-0.44	17	17
ADCY9	-0.011	0.12	-9999	-0.46	13	13
GSK3B	0.005	0.074	-9999	-10000	0	0
arachidonic acid secretion	-0.003	0.12	-9999	-0.44	13	13
GNG2	0.013	0.001	-9999	-10000	0	0
TRIP6	0.017	0.024	-9999	-10000	0	0
GNAO1	-0.033	0.14	-9999	-0.46	13	13
HRAS	0.012	0.04	-9999	-0.82	1	1
NFKBIA	0.014	0.084	-9999	-0.42	3	3
GAB1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.006	0.098	-9999	-0.9	5	5
JUN	0.014	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.015	0.044	-9999	-0.64	1	1
TIAM1	-0.009	0.12	-9999	-1.1	5	5
PIK3R1	0.009	0.051	-9999	-0.59	3	3
mol:IP3	0.009	0.073	-9999	-0.44	3	3
PLCB3	0.013	0.046	-9999	-0.58	1	1
FOS	-0.068	0.21	-9999	-0.59	57	57
positive regulation of mitosis	-0.003	0.12	-9999	-0.44	13	13
LPA/LPA1-2-3	-0.053	0.11	-9999	-0.68	3	3
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0	-9999	-10000	0	0
stress fiber formation	0.002	0.09	-9999	-0.39	3	3
GNAZ	-0.047	0.16	-9999	-0.51	24	24
EGFR/PI3K-beta/Gab1	-0.055	0.11	-9999	-0.54	5	5
positive regulation of dendritic cell cytokine production	-0.052	0.11	-9999	-0.67	3	3
LPA/LPA2/MAGI-3	-0.016	0.04	-9999	-0.36	2	2
ARHGEF1	-0.012	0.12	-9999	-0.56	5	5
GNAI2	-0.028	0.13	-9999	-0.41	9	9
GNAI3	-0.028	0.13	-9999	-0.42	8	8
GNAI1	-0.029	0.13	-9999	-0.4	10	10
LPA/LPA3	-0.028	0.073	-9999	-0.44	8	8
LPA/LPA2	-0.019	0.044	-9999	-10000	0	0
LPA/LPA1	-0.065	0.14	-9999	-0.36	77	77
HB-EGF/EGFR	-0.4	0.27	-9999	-0.56	312	312
HBEGF	-0.45	0.29	-9999	-0.63	309	309
mol:DAG	0.009	0.073	-9999	-0.44	3	3
cAMP biosynthetic process	-0.025	0.12	-9999	-0.5	12	12
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.013	0.001	-9999	-10000	0	0
LYN	0.013	0.086	-9999	-0.42	3	3
GNAQ	0.004	0.058	-9999	-0.31	8	8
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	0.002	0.082	-9999	-0.59	8	8
LPAR1	-0.026	0.12	-9999	-0.63	9	9
IL8	-0.23	0.18	-9999	-0.5	77	77
PTK2	-0.013	0.12	-9999	-0.63	3	3
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.022	0.12	-9999	-0.61	3	3
EGFR	-0.017	0.15	-9999	-0.79	16	16
PLCG1	-0.008	0.078	-9999	-0.36	8	8
PLD2	-0.013	0.12	-9999	-0.63	3	3
G12/G13	-0.051	0.11	-9999	-0.61	5	5
PI3K-beta	-0.035	0.077	-9999	-0.56	2	2
cell migration	-0.01	0.046	-9999	-0.28	1	1
SLC9A3R2	0.012	0.04	-9999	-0.82	1	1
PXN	0.001	0.092	-9999	-0.4	3	3
HRAS/GTP	-0.004	0.12	-9999	-0.45	13	13
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.59	0.37	-9999	-0.82	309	309
PRKCE	0.013	0.001	-9999	-10000	0	0
PRKCD	0.017	0.069	-9999	-0.47	1	1
Gi(beta/gamma)	-0.006	0.12	-9999	-0.43	13	13
mol:LPA	-0.029	0.077	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.028	0.086	-9999	-0.53	3	3
MAPKKK cascade	-0.003	0.12	-9999	-0.44	13	13
contractile ring contraction involved in cytokinesis	0.007	0.061	-9999	-0.32	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.049	0.13	-9999	-0.31	75	75
GNA15	0.003	0.067	-9999	-0.36	9	9
GNA12	0.006	0.08	-9999	-0.82	4	4
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.12	0.16	-9999	-0.44	27	27
GNA11	0.002	0.063	-9999	-0.31	11	11
Rac1/GTP	-0.007	0.1	-9999	-0.96	5	5
MMP2	-0.11	0.3	-9999	-0.76	69	69

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.048	0.23	-10000	0	-0.91	17	17
NCK1/PAK1/Dok-R	-0.029	0.09	-10000	0	-0.42	17	17
NCK1/Dok-R	-0.052	0.23	-10000	0	-1.1	17	17
PIK3CA	0.013	0.002	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.005	0.041	0.24	10	-10000	0	10
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0.002	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.082	0.25	-10000	0	-0.84	42	42
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.045	0.2	-10000	0	-1	17	17
FN1	-0.39	0.42	-10000	0	-0.82	207	207
PLD2	0.031	0.26	-10000	0	-1.2	17	17
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.051	0.19	-10000	0	-0.63	42	42
ELK1	0.046	0.23	-10000	0	-1	17	17
GRB7	0.004	0.085	-10000	0	-0.77	5	5
PAK1	0.012	0.04	-10000	0	-0.82	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.36	0.37	-10000	0	-0.86	122	122
CDKN1A	0.054	0.2	-10000	0	-0.66	9	9
ITGA5	-0.26	0.39	-10000	0	-0.82	137	137
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.052	0.23	-10000	0	-1.1	17	17
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	0.056	0.19	-10000	0	-0.66	17	17
PLG	0.02	0.26	-10000	0	-1.2	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.031	0.21	-10000	0	-0.87	17	17
GRB2	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.051	-10000	0	-0.59	3	3
ANGPT2	0.006	0.21	-10000	0	-0.61	27	27
BMX	-0.005	0.28	-10000	0	-1.2	17	17
ANGPT1	0.015	0.23	-10000	0	-1.3	12	12
tube development	0.046	0.22	-10000	0	-0.74	11	11
ANGPT4	0.008	0.008	-10000	0	-10000	0	0
response to hypoxia	0.001	0.015	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.007	0.28	-10000	0	-1.2	17	17
alpha5/beta1 Integrin	-0.2	0.29	-10000	0	-0.63	138	138
FGF2	-0.011	0.12	-10000	0	-0.65	15	15
STAT5A (dimer)	0.048	0.23	-10000	0	-0.87	9	9
mol:L-citrulline	0.056	0.19	-10000	0	-0.66	17	17
AGTR1	-0.051	0.19	-10000	0	-0.61	43	43
MAPK14	0.033	0.26	-10000	0	-1.2	17	17
Tie2/SHP2	-0.031	0.18	-10000	0	-1.2	9	9
TEK	0.012	0.21	-10000	0	-1.4	9	9
RPS6KB1	0.053	0.22	-10000	0	-0.87	17	17
Angiotensin II/AT1	-0.037	0.14	-10000	0	-0.45	43	43
Tie2/Ang1/GRB2	0.026	0.26	-10000	0	-1.2	17	17
MAPK3	0.04	0.23	-10000	0	-1	17	17
MAPK1	0.04	0.23	-10000	0	-1	17	17
Tie2/Ang1/GRB7	0.022	0.27	-10000	0	-1.2	17	17
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.027	0.27	-10000	0	-1.2	17	17
PI3K	0.041	0.26	-10000	0	-1.1	17	17
FES	0.033	0.26	-10000	0	-1.1	17	17
Crk/Dok-R	-0.052	0.23	-10000	0	-1.1	17	17
Tie2/Ang1/ABIN2	0.026	0.26	-10000	0	-1.2	17	17
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.052	0.21	-10000	0	-0.8	17	17
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.053	0.22	-10000	0	-0.87	17	17
Tie2/Ang2	0.029	0.27	-10000	0	-1.1	10	10
Tie2/Ang1	0.023	0.28	-10000	0	-1.3	17	17
FOXO1	0.052	0.22	-10000	0	-0.8	17	17
ELF1	0.018	0.055	-10000	0	-0.61	3	3
ELF2	0.028	0.26	-10000	0	-1.2	17	17
mol:Choline	0.034	0.24	-10000	0	-1.1	17	17
cell migration	-0.096	0.088	-10000	0	-10000	0	0
FYN	0.042	0.24	-10000	0	-0.86	11	11
DOK2	0.007	0.07	-10000	0	-0.7	4	4
negative regulation of cell cycle	0.056	0.18	-10000	0	-0.6	9	9
ETS1	0.013	0.078	-10000	0	-0.8	3	3
PXN	0.063	0.19	-10000	0	-0.71	17	17
ITGB1	0.012	0.04	-10000	0	-0.82	1	1
NOS3	0.053	0.21	-10000	0	-0.75	17	17
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.02	0.18	-10000	0	-0.77	21	21
MAPKKK cascade	0.034	0.24	-10000	0	-1.1	17	17
RASA1	0.012	0.029	-10000	0	-0.59	1	1
Tie2/Ang1/Shc	0.027	0.26	-10000	0	-1.2	17	17
NCK1	0.014	0	-10000	0	-10000	0	0
vasculogenesis	0.058	0.17	-10000	0	-0.58	17	17
mol:Phosphatidic acid	0.034	0.24	-10000	0	-1.1	17	17
mol:Angiotensin II	0	0.008	-10000	0	-10000	0	0
mol:NADP	0.056	0.19	-10000	0	-0.66	17	17
Rac1/GTP	-0.05	0.17	-10000	0	-0.8	17	17
MMP2	-0.048	0.3	-10000	0	-1.2	17	17

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.02	0.005	-9999	-10000	0	0
RAS family/GTP	-0.023	0.12	-9999	-0.48	4	4
NFATC4	-0.021	0.13	-9999	-0.45	5	5
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.045	0.15	-9999	-0.39	12	12
JUN	0.004	0.084	-9999	-0.38	5	5
HRAS	0.011	0.04	-9999	-0.82	1	1
DOCK7	-0.036	0.14	-9999	-0.57	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.087	0.18	-9999	-0.47	73	73
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.041	0.076	-9999	-0.31	6	6
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.047	0.16	-9999	-0.42	12	12
RAF1	-0.021	0.12	-9999	-0.56	2	2
ErbB2/ErbB3/neuregulin 2	-0.2	0.17	-9999	-0.36	78	78
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.005	0.087	-9999	-0.26	3	3
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.14	0.28	-9999	-0.58	84	84
FOS	-0.1	0.23	-9999	-0.48	72	72
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.045	0.15	-9999	-0.39	12	12
MAPK3	-0.1	0.23	-9999	-0.53	32	32
MAPK1	-0.1	0.23	-9999	-0.53	32	32
JAK2	-0.036	0.14	-9999	-0.57	1	1
NF2	-0.003	0.005	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.03	0.13	-9999	-0.29	73	73
NRG1	-0.13	0.31	-9999	-0.81	73	73
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.02	0.11	-9999	-0.45	2	2
MAPK9	-0.031	0.064	-9999	-0.26	1	1
ERBB2	-0.005	0.054	-9999	-0.64	3	3
ERBB3	0.003	0.072	-9999	-0.59	6	6
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	0.009	0.01	-9999	-10000	0	0
STAT3 (dimer)	0.003	0.006	-9999	-10000	0	0
RNF41	0.026	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.044	0.091	-9999	-0.38	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.004	0.046	-9999	-0.55	3	3
CHRNA1	-0.15	0.3	-9999	-0.54	139	139
myelination	-0.012	0.12	-9999	-0.46	3	3
PPP3CB	-0.033	0.13	-9999	-0.52	1	1
KRAS	0.009	0.057	-9999	-0.82	2	2
RAC1-CDC42/GDP	-0.011	0.11	-9999	-0.61	1	1
NRG2	-0.34	0.3	-9999	-0.59	251	251
mol:GDP	-0.03	0.12	-9999	-0.29	73	73
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.025	0.13	-9999	-0.55	2	2
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.036	0.14	-9999	-0.57	1	1
MAP2K1	-0.089	0.2	-9999	-0.51	20	20
heart morphogenesis	-0.045	0.15	-9999	-0.39	12	12
RAS family/GDP	-0.02	0.11	-9999	-0.48	4	4
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.009	-9999	-10000	0	0
CHRNE	0.011	0.031	-9999	-0.23	5	5
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.045	0.15	-9999	-0.39	12	12
CDC42	0.014	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.009	0.062	-10000	0	-0.59	3	3
HDAC1	0.009	0.005	-10000	0	-10000	0	0
AES	0.013	0.001	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
DTX1	0.011	0.041	-10000	0	-0.59	2	2
LRP6/FZD1	-0.008	0.071	-10000	0	-0.59	6	6
TLE1	0.013	0.001	-10000	0	-10000	0	0
AP1	-0.027	0.12	-10000	0	-0.7	1	1
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.012	0.029	-10000	0	-0.59	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.045	-10000	0	-10000	0	0
NICD/RBPSUH	-0.005	0.052	-10000	0	-0.59	3	3
WIF1	-0.27	0.31	-10000	0	-0.61	188	188
NOTCH1	-0.005	0.055	-10000	0	-0.56	4	4
PSENEN	0.012	0.04	-10000	0	-0.82	1	1
KREMEN2	-0.28	0.4	-10000	0	-0.82	149	149
DKK1	-0.25	0.38	-10000	0	-0.79	138	138
beta catenin/beta TrCP1	0.021	0.047	-10000	0	-0.35	1	1
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	0.001	0.026	-10000	0	-0.28	1	1
CtBP/CBP/TCF1/TLE1/AES	0.02	0.042	-10000	0	-10000	0	0
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.068	0.21	-10000	0	-0.59	57	57
JUN	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.012	0.002	-10000	0	-10000	0	0
CTNNB1	0.014	0.05	-10000	0	-0.38	1	1
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.21	0.27	-10000	0	-0.55	158	158
HNF1A	-0.001	0.11	-10000	0	-0.82	7	7
CTBP1	0.013	0.001	-10000	0	-10000	0	0
MYC	0.025	0.013	-10000	0	-10000	0	0
NKD1	-0.021	0.16	-10000	0	-0.79	18	18
FZD1	0.004	0.09	-10000	0	-0.82	5	5
NOTCH1 precursor/Deltex homolog 1	-0.006	0.062	-10000	0	-0.68	3	3
apoptosis	-0.027	0.12	-10000	0	-0.69	1	1
Delta 1/NOTCHprecursor	-0.009	0.062	-10000	0	-0.59	3	3
DLL1	0.005	0.071	-10000	0	-0.59	6	6
PPARD	0.025	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.022	-10000	0	-0.46	1	1
APC	0	0.033	-10000	0	-0.35	2	2
DVL1	-0.019	0.029	-10000	0	-10000	0	0
CSNK2A1	0.014	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.35	0.34	-10000	0	-0.64	230	230
LRP6	0.012	0.029	-10000	0	-0.59	1	1
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.006	0.14	-10000	0	-0.79	11	11
WNT1	-0.002	0.098	-10000	0	-0.82	6	6
Axin1/APC/beta catenin	0.026	0.042	-10000	0	-0.4	1	1
DKK2	-0.016	0.15	-10000	0	-0.72	17	17
NOTCH1 precursor/DVL1	-0.01	0.051	-10000	0	-0.58	3	3
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.007	0.063	-10000	0	-0.69	3	3
PPP2R5D	0.003	0.069	0.32	18	-10000	0	18
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.16	0.17	-10000	0	-0.49	24	24
RBPJ	0.014	0	-10000	0	-10000	0	0
CREBBP	0.017	0.003	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	0.004	0.077	-9999	-0.59	7	7
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.077	0.16	-9999	-0.39	83	83
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.014	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.039	0.16	-9999	-0.57	11	11
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.02	0.15	-9999	-0.82	15	15
IQGAP1	0.014	0	-9999	-10000	0	0
PLA2G7	-0.32	0.41	-9999	-0.82	173	173
CALM1	0.014	0	-9999	-10000	0	0
DYNLT1	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.013	0.09	-9999	-0.63	9	9
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0.041	-9999	-0.59	2	2
CDK5R1	0.012	0.04	-9999	-0.82	1	1
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	-0.11	0.29	-9999	-0.82	61	61
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.091	0.18	-9999	-0.4	95	95
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.04	0.16	-9999	-0.58	13	13
MAP1B	-0.007	0.046	-9999	-0.3	10	10
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.02	0.14	-9999	-0.64	4	4
RELN	-0.098	0.24	-9999	-0.6	77	77
PAFAH/LIS1	-0.2	0.28	-9999	-0.54	173	173
LIS1/CLIP170	0.027	0.026	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.061	0.1	-9999	-0.51	7	7
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.026	0.13	-9999	-0.57	4	4
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.051	0.17	-9999	-0.64	13	13
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	0.012	0.04	-9999	-0.82	1	1
PAFAH1B2	0.012	0.029	-9999	-0.59	1	1
MAP1B/LIS1/Dynein heavy chain	0.022	0.033	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.077	0.13	-9999	-0.56	13	13
LRP8	-0.004	0.12	-9999	-0.82	9	9
NDEL1/Katanin 60	-0.04	0.16	-9999	-0.58	13	13
P39/CDK5	-0.09	0.22	-9999	-0.52	62	62
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.028	0.15	-9999	-0.53	11	11
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.001	0.021	-9999	-10000	0	0
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.075	0.15	-9999	-0.52	18	18
RELN/VLDLR	-0.074	0.15	-9999	-0.58	12	12
CDC42	0	0	-9999	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.032	0.14	-9999	-0.6	8	8
FZD6	0.014	0	-9999	-10000	0	0
WNT6	-0.043	0.2	-9999	-0.76	31	31
WNT4	-0.008	0.12	-9999	-0.66	14	14
FZD3	0.006	0.065	-9999	-0.59	5	5
WNT5A	0.005	0.076	-9999	-0.68	5	5
WNT11	-0.076	0.25	-9999	-0.76	49	49

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.003	-9999	-10000	0	0
SMARCC1	0.011	0.011	-9999	-10000	0	0
REL	0.008	0.072	-9999	-0.59	6	6
HDAC7	-0.072	0.16	-9999	-0.58	15	15
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.01	0.041	-9999	-0.59	2	2
KAT2B	-0.015	0.13	-9999	-0.59	20	20
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.008	0.1	-9999	-0.45	20	20
FOXO1	0.013	0.001	-9999	-10000	0	0
T-DHT/AR	-0.086	0.17	-9999	-0.57	23	23
MAP2K6	-0.021	0.13	-9999	-0.61	20	20
BRM/BAF57	-0.002	0.021	-9999	-0.43	1	1
MAP2K4	0.008	0.008	-9999	-10000	0	0
SMARCA2	0.01	0.03	-9999	-0.59	1	1
PDE9A	-0.096	0.2	-9999	-1.1	13	13
NCOA2	-0.024	0.14	-9999	-0.59	26	26
CEBPA	0.01	0.051	-9999	-0.59	3	3
EHMT2	0.011	0.005	-9999	-10000	0	0
cell proliferation	-0.064	0.17	-9999	-0.51	18	18
NR0B1	-0.032	0.17	-9999	-0.82	19	19
EGR1	-0.013	0.12	-9999	-0.59	17	17
RXRs/9cRA	-0.039	0.11	-9999	-0.39	18	18
AR/RACK1/Src	-0.037	0.12	-9999	-0.48	14	14
AR/GR	-0.062	0.15	-9999	-0.54	13	13
GNB2L1	0.014	0.002	-9999	-10000	0	0
PKN1	0.011	0.04	-9999	-0.82	1	1
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.006	0.062	-9999	-0.46	7	7
T-DHT/AR/TIF2/CARM1	-0.052	0.16	-9999	-0.58	18	18
SRC	-0.004	0.096	-9999	-0.59	1	1
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.29	0.46	-9999	-1.2	80	80
APPBP2	0.008	0.008	-9999	-10000	0	0
TRIM24	0.01	0.03	-9999	-0.59	1	1
T-DHT/AR/TIP60	-0.039	0.13	-9999	-0.52	13	13
TMPRSS2	-0.55	0.56	-9999	-1.1	212	212
RXRG	-0.058	0.2	-9999	-0.62	47	47
mol:9cRA	-0.001	0.003	-9999	-10000	0	0
RXRA	0.013	0.001	-9999	-10000	0	0
RXRB	0.013	0.001	-9999	-10000	0	0
CARM1	0.014	0.002	-9999	-10000	0	0
NR2C2	0.006	0.065	-9999	-0.59	5	5
KLK2	-0.038	0.17	-9999	-0.62	20	20
AR	-0.078	0.16	-9999	-0.38	65	65
SENP1	0.013	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.018	0.012	-9999	-10000	0	0
SRY	-0.034	0.16	-9999	-0.6	31	31
GATA2	0.004	0.085	-9999	-0.77	5	5
MYST2	0.013	0.029	-9999	-0.59	1	1
HOXB13	-0.29	0.4	-9999	-0.82	149	149
T-DHT/AR/RACK1/Src	-0.03	0.12	-9999	-0.5	13	13
positive regulation of transcription	0.004	0.085	-9999	-0.77	5	5
DNAJA1	0.008	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.004	-9999	-10000	0	0
NCOA1	0.017	0.008	-9999	-10000	0	0
SPDEF	-0.2	0.3	-9999	-0.61	142	142
T-DHT/AR/TIF2	-0.03	0.15	-9999	-0.58	15	15
T-DHT/AR/Hsp90	-0.04	0.13	-9999	-0.52	13	13
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.014	0.1	-9999	-0.46	4	4
SIRT1	0.012	0.029	-9999	-0.59	1	1
ZMIZ2	0.018	0.011	-9999	-10000	0	0
POU2F1	0.015	0.022	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.077	0.15	-9999	-0.51	34	34
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.011	0.005	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.16	0.34	-10000	0	-0.82	90	90
Jak2/Leptin Receptor	-0.067	0.1	-10000	0	-0.46	4	4
PTP1B/AKT1	-0.022	0.082	0.23	1	-0.35	2	3
FYN	0.012	0.04	-10000	0	-0.82	1	1
p210 bcr-abl/PTP1B	-0.033	0.091	0.26	1	-0.36	5	6
EGFR	-0.019	0.15	-10000	0	-0.79	16	16
EGF/EGFR	-0.1	0.15	-10000	0	-0.44	41	41
CSF1	0.006	0.065	-10000	0	-0.59	5	5
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.014	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.091	0.2	0.23	1	-0.54	60	61
Insulin Receptor/Insulin	-0.033	0.055	-10000	0	-0.47	1	1
HCK	0.007	0.07	-10000	0	-0.7	4	4
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.024	0.09	0.25	1	-0.38	5	6
EGF	-0.099	0.24	-10000	0	-0.6	77	77
YES1	0.014	0	-10000	0	-10000	0	0
CAV1	-0.049	0.11	0.25	1	-0.37	12	13
TXN	0.011	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.018	0.083	-10000	0	-0.37	1	1
cell migration	0.033	0.091	0.36	5	-0.26	1	6
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.11	0.25	-10000	0	-0.6	85	85
ITGA2B	-0.054	0.22	-10000	0	-0.82	34	34
CSF1R	0.009	0.051	-10000	0	-0.59	3	3
Prolactin Receptor/Prolactin	-0.092	0.19	-10000	0	-0.46	87	87
FGR	0.012	0.04	-10000	0	-0.82	1	1
PTP1B/p130 Cas	-0.024	0.086	0.23	1	-0.35	4	5
Crk/p130 Cas	-0.016	0.082	-10000	0	-0.37	1	1
DOK1	-0.059	0.14	0.25	1	-0.4	16	17
JAK2	-0.06	0.12	-10000	0	-0.38	15	15
Jak2/Leptin Receptor/Leptin	-0.077	0.12	-10000	0	-0.47	3	3
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
PTPN1	-0.033	0.092	0.26	1	-0.36	5	6
LYN	0.012	0.029	-10000	0	-0.59	1	1
CDH2	-0.1	0.29	-10000	0	-0.8	61	61
SRC	0.004	0.037	-10000	0	-10000	0	0
ITGB3	-0.023	0.16	-10000	0	-0.74	20	20
CAT1/PTP1B	-0.12	0.14	0.26	1	-0.43	21	22
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.025	0.057	-10000	0	-0.52	1	1
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.068	0.1	-10000	0	-0.43	1	1
negative regulation of transcription	-0.06	0.11	-10000	0	-0.38	15	15
FCGR2A	-0.033	0.19	-10000	0	-0.82	24	24
FER	0.009	0.03	-10000	0	-0.6	1	1
alphaIIb/beta3 Integrin	-0.076	0.21	-10000	0	-0.62	52	52
BLK	-0.11	0.28	-10000	0	-0.78	64	64
Insulin Receptor/Insulin/Shc	-0.002	0.037	-10000	0	-0.53	2	2
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	0.012	0.029	-10000	0	-0.59	1	1
BCAR1	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.014	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.004	-10000	0	-10000	0	0
TRPV6	-0.11	0.15	-10000	0	-0.44	33	33
PRL	-0.004	0.08	-10000	0	-0.81	4	4
SOCS3	0.018	0.068	-10000	0	-1.3	1	1
SPRY2	0.003	0.078	-10000	0	-0.6	7	7
Insulin Receptor/Insulin/IRS1	-0.004	0.044	-10000	0	-0.53	2	2
CSF1/CSF1R	-0.022	0.092	-10000	0	-0.41	4	4
Ras protein signal transduction	0.027	0.029	-10000	0	-10000	0	0
IRS1	0.011	0.041	-10000	0	-0.59	2	2
INS	-0.003	0.056	-10000	0	-0.82	2	2
LEP	-0.099	0.26	-10000	0	-0.68	67	67
STAT5B	-0.04	0.085	0.21	1	-0.34	6	7
STAT5A	-0.04	0.085	0.21	1	-0.34	6	7
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.12	0.24	0.23	1	-0.57	92	93
CSN2	-0.024	0.093	-10000	0	-0.74	2	2
PIK3CA	0.014	0	-10000	0	-10000	0	0
LAT	-0.018	0.088	-10000	0	-0.33	15	15
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.006	0.13	-10000	0	-0.82	10	10
SHC1	0.014	0	-10000	0	-10000	0	0
NOX4	-0.18	0.35	-10000	0	-0.82	98	98

×

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	-0.023	0.095	-9999	-0.41	24	24
EFNA5	-0.013	0.12	-9999	-0.59	19	19
FYN	0	0.1	-9999	-0.59	5	5
neuron projection morphogenesis	-0.023	0.095	-9999	-0.41	24	24
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.023	0.096	-9999	-0.41	24	24
EPHA5	-0.002	0.089	-9999	-0.82	5	5

×

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	-0.006	0.046	-9999	-0.36	7	7
ARNO/beta Arrestin1-2	-0.018	0.069	-9999	-0.53	1	1
EGFR	-0.017	0.15	-9999	-0.79	16	16
EPHA2	0.005	0.071	-9999	-0.59	6	6
USP6	0.014	0.001	-9999	-10000	0	0
IQSEC1	0.014	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.1	0.2	-9999	-0.46	92	92
ARRB2	0.01	0.003	-9999	-10000	0	0
mol:GTP	0.019	0.022	-9999	-0.16	2	2
ARRB1	0.011	0.041	-9999	-0.59	2	2
FBXO8	0.014	0	-9999	-10000	0	0
TSHR	-0.03	0.18	-9999	-0.82	21	21
EGF	-0.098	0.24	-9999	-0.6	77	77
somatostatin receptor activity	0	0	-9999	-0.001	12	12
ARAP2	0.008	0.058	-9999	-0.59	4	4
mol:GDP	-0.015	0.081	-9999	-0.33	11	11
mol:PI-3-4-5-P3	0	0	-9999	-0.001	7	7
ITGA2B	-0.053	0.23	-9999	-0.82	34	34
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.044	-9999	-0.49	1	1
ADAP1	0.012	0.029	-9999	-0.59	1	1
KIF13B	0.005	0.071	-9999	-0.59	6	6
HGF/MET	-0.024	0.11	-9999	-0.51	20	20
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.028	0.11	-9999	-0.33	13	13
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.085	0.17	-9999	-0.56	16	16
ADRB2	-0.026	0.15	-9999	-0.59	28	28
receptor agonist activity	0	0	-9999	0	13	13
actin filament binding	0	0	-9999	-0.001	12	12
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.022	0.16	-9999	-0.74	20	20
GNAQ	0.014	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	9	9
ARF6/GDP	0.042	0.064	-9999	-0.37	3	3
ARF6/GDP/GULP/ACAP1	-0.12	0.16	-9999	-0.45	38	38
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.06	0.16	-9999	-0.51	46	46
ACAP1	-0.004	0.12	-9999	-0.82	9	9
ACAP2	0.012	0.04	-9999	-0.82	1	1
LHCGR/beta Arrestin2	0.002	0.006	-9999	-10000	0	0
EFNA1	0.012	0.04	-9999	-0.82	1	1
HGF	-0.012	0.13	-9999	-0.66	16	16
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.01	0.002	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	-0.001	11	11
endosomal lumen acidification	0	0	-9999	-0.001	12	12
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.17	0.28	-9999	-0.59	131	131
GNAQ/ARNO	0.015	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	1	1
MET	0.006	0.075	-9999	-0.76	4	4
GNA14	-0.083	0.22	-9999	-0.59	68	68
GNA15	0.011	0.041	-9999	-0.59	2	2
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	11	11
GNA11	0.009	0.051	-9999	-0.59	3	3
LHCGR	0.002	0.005	-9999	-10000	0	0
AGTR1	-0.051	0.19	-9999	-0.61	43	43
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.006	-9999	-10000	0	0
IPCEF1/ARNO	-0.049	0.14	-9999	-0.44	16	16
alphaIIb/beta3 Integrin	-0.076	0.21	-9999	-0.62	52	52

×

EPO 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.13	-10000	0	-0.56	2	2
CRKL	-0.003	0.14	-10000	0	-0.46	2	2
mol:DAG	0.008	0.13	-10000	0	-0.57	2	2
HRAS	0.027	0.13	-10000	0	-0.58	1	1
MAPK8	-0.026	0.17	-10000	0	-0.47	52	52
RAP1A	-0.002	0.14	-10000	0	-0.49	1	1
GAB1	-0.002	0.14	-10000	0	-0.49	1	1
MAPK14	-0.021	0.16	-10000	0	-0.46	52	52
EPO	-0.071	0.25	-10000	0	-0.81	44	44
PLCG1	0.008	0.14	-10000	0	-0.59	2	2
EPOR/TRPC2/IP3 Receptors	-0.003	0.11	-10000	0	-0.81	8	8
RAPGEF1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.061	0.17	-10000	0	-0.51	52	52
GAB1/SHC/GRB2/SOS1	-0.041	0.11	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.053	0.21	-10000	0	-0.62	52	52
IRS2	-0.004	0.14	-10000	0	-0.49	1	1
STAT1	-0.009	0.17	-10000	0	-0.64	4	4
STAT5B	0.012	0.14	-10000	0	-0.62	2	2
cell proliferation	-0.016	0.16	-10000	0	-0.44	52	52
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.041	0.11	-10000	0	-0.59	3	3
TEC	-0.02	0.17	-10000	0	-0.69	7	7
SOCS3	0.012	0.029	-10000	0	-0.59	1	1
STAT1 (dimer)	-0.008	0.16	-10000	0	-0.62	4	4
JAK2	0.01	0.032	-10000	0	-0.59	1	1
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
EPO/EPOR (dimer)/JAK2	0.001	0.16	-10000	0	-0.4	53	53
EPO/EPOR	-0.053	0.21	-10000	0	-0.62	52	52
LYN	0.014	0.029	-10000	0	-0.59	1	1
TEC/VAV2	-0.024	0.19	-10000	0	-0.77	9	9
elevation of cytosolic calcium ion concentration	-0.003	0.11	-10000	0	-0.8	8	8
SHC1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.029	0.18	-10000	0	-0.52	52	52
mol:IP3	0.008	0.13	-10000	0	-0.57	2	2
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.047	0.12	-10000	0	-0.65	3	3
SH2B3	0.009	0.042	-10000	0	-0.81	1	1
NFKB1	-0.021	0.16	-10000	0	-0.46	52	52
EPO/EPOR (dimer)/JAK2/SOCS3	-0.034	0.092	0.28	1	-0.29	45	46
PTPN6	-0.011	0.15	-10000	0	-0.4	53	53
TEC/VAV2/GRB2	-0.017	0.18	-10000	0	-0.74	9	9
EPOR	-0.003	0.11	-10000	0	-0.81	8	8
INPP5D	0.011	0.041	-10000	0	-0.59	2	2
mol:GDP	-0.042	0.11	-10000	0	-10000	0	0
SOS1	0.014	0	-10000	0	-10000	0	0
PLCG2	0.012	0.029	-10000	0	-0.59	1	1
CRKL/CBL/C3G	0.012	0.14	-10000	0	-0.45	1	1
VAV2	-0.015	0.17	-10000	0	-0.52	13	13
CBL	-0.002	0.14	-10000	0	-0.49	1	1
SHC/Grb2/SOS1	-0.044	0.11	-10000	0	-10000	0	0
STAT5A	0.012	0.14	-10000	0	-0.62	2	2
GRB2	0.014	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.03	0.14	-10000	0	-0.65	2	2
LYN/PLCgamma2	-0.002	0.029	-10000	0	-0.43	2	2
PTPN11	0.014	0	-10000	0	-10000	0	0
BTK	-0.003	0.14	-10000	0	-0.49	1	1
BCL2	0.016	0.16	-10000	0	-0.71	9	9

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.002	0.092	-9999	-0.66	8	8
PDGF/PDGFRA/CRKL	-0.01	0.072	-9999	-0.49	9	9
positive regulation of JUN kinase activity	-0.007	0.048	-9999	-0.46	2	2
CRKL	0.012	0.04	-9999	-0.82	1	1
PDGF/PDGFRA/Caveolin-3	-0.11	0.2	-9999	-0.45	102	102
AP1	-0.14	0.33	-9999	-0.97	57	57
mol:IP3	0.011	0.073	-9999	-0.49	8	8
PLCG1	0.011	0.074	-9999	-0.49	8	8
PDGF/PDGFRA/alphaV Integrin	-0.014	0.091	-9999	-0.55	11	11
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	0.011	0.073	-9999	-0.49	8	8
CAV3	-0.13	0.25	-9999	-0.6	96	96
CAV1	-0.065	0.24	-9999	-0.82	40	40
SHC/Grb2/SOS1	-0.007	0.048	-9999	-0.46	2	2
PDGF/PDGFRA/Shf	-0.017	0.094	-9999	-0.51	14	14
FOS	-0.09	0.34	-9999	-0.96	57	57
JUN	-0.008	0.021	-9999	-10000	0	0
oligodendrocyte development	-0.014	0.091	-9999	-0.55	11	11
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
mol:DAG	0.011	0.073	-9999	-0.49	8	8
PDGF/PDGFRA	-0.002	0.092	-9999	-0.66	8	8
actin cytoskeleton reorganization	-0.012	0.074	-9999	-0.46	11	11
SRF	0.025	0.009	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
PI3K	-0.01	0.062	-9999	-0.41	7	7
PDGF/PDGFRA/Crk/C3G	-0.007	0.054	-9999	-0.44	4	4
JAK1	0.014	0.068	-9999	-0.47	8	8
ELK1/SRF	0.032	0.059	-9999	-0.44	3	3
SHB	0.009	0.051	-9999	-0.59	3	3
SHF	0.002	0.082	-9999	-0.59	8	8
CSNK2A1	0.008	0.02	-9999	-10000	0	0
GO:0007205	0.011	0.075	-9999	-0.5	8	8
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.007	0.048	-9999	-0.46	2	2
PDGF/PDGFRA/SHB	-0.012	0.074	-9999	-0.46	11	11
PDGF/PDGFRA/Caveolin-1	-0.069	0.2	-9999	-0.61	48	48
ITGAV	0.006	0.075	-9999	-0.76	4	4
ELK1	0.014	0.079	-9999	-0.46	9	9
PIK3CA	0.014	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.009	0.065	-9999	-0.47	8	8
JAK-STAT cascade	0.014	0.068	-9999	-0.47	8	8
cell proliferation	-0.017	0.093	-9999	-0.51	14	14

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.011	0.041	-10000	0	-0.59	2	2
HDAC4	0.014	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.015	0.15	0.62	24	-10000	0	24
CDKN1A	0.001	0.013	-10000	0	-10000	0	0
KAT2B	-0.015	0.13	-10000	0	-0.59	20	20
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.002	0.031	0.45	2	-10000	0	2
FOXO1	0.014	0	-10000	0	-10000	0	0
FOXO4	0.022	0.031	-10000	0	-0.29	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
TAT	-0.004	0.098	-10000	0	-0.82	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.075	0.19	-10000	0	-0.46	84	84
PPARGC1A	-0.19	0.29	-10000	0	-0.59	145	145
FHL2	0.011	0.041	-10000	0	-0.59	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.021	-10000	0	-0.43	1	1
HIST2H4A	-0.015	0.15	-10000	0	-0.62	24	24
SIRT1/FOXO3a	0.001	0.027	0.29	2	-0.36	1	3
SIRT1	-0.001	0.029	-10000	0	-0.59	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.017	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.012	0.054	-10000	0	-0.35	1	1
apoptosis	0.001	0.017	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.13	0.18	-10000	0	-0.37	145	145
p53/SIRT1	-0.005	0.046	-10000	0	-0.43	5	5
SIRT1/FOXO4	-0.003	0.029	-10000	0	-0.35	1	1
FOXO1/FHL2/SIRT1	-0.002	0.027	-10000	0	-10000	0	0
HIST1H1E	0.009	0.067	-10000	0	-0.29	21	21
SIRT1/p300	-0.003	0.036	-10000	0	-0.43	3	3
muscle cell differentiation	0.076	0.16	0.61	8	-10000	0	8
TP53	-0.006	0.057	-10000	0	-0.59	4	4
KU70/SIRT1/BAX	-0.001	0.017	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.014	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.01	0.077	-10000	0	-0.6	7	7
ACSS2	0.021	0.022	-10000	0	-0.43	1	1
SIRT1/PCAF/MYOD	-0.077	0.16	-10000	0	-0.62	8	8

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.003	0.12	-10000	0	-0.79	9	9
positive regulation of NF-kappaB transcription factor activity	-0.032	0.14	-10000	0	-0.6	23	23
MAP2K4	0.009	0.099	-10000	0	-10000	0	0
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.014	0	-10000	0	-10000	0	0
TNFRSF10A	0.012	0.029	-10000	0	-0.59	1	1
SMPD1	0.016	0.039	-10000	0	-0.26	8	8
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.013	0.14	-10000	0	-0.78	14	14
TRAIL/TRAILR2	-0.013	0.088	-10000	0	-0.6	9	9
TRAIL/TRAILR3	-0.03	0.13	-10000	0	-0.61	21	21
TRAIL/TRAILR1	-0.014	0.09	-10000	0	-0.59	10	10
TRAIL/TRAILR4	-0.033	0.14	-10000	0	-0.6	23	23
TRAIL/TRAILR1/DAP3/GTP	-0.011	0.071	-10000	0	-0.46	10	10
IKK complex	-0.026	0.063	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.011	0.091	-10000	0	-0.6	9	9
MAP3K1	0.001	0.1	-10000	0	-10000	0	0
TRAILR4 (trimer)	-0.013	0.14	-10000	0	-0.78	14	14
TRADD	0.014	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.012	0.029	-10000	0	-0.59	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.11	-10000	0	-10000	0	0
CFLAR	0.014	0	-10000	0	-10000	0	0
MAPK1	0.011	0.091	-10000	0	-0.6	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.066	0.16	-10000	0	-0.46	60	60
mol:ceramide	0.016	0.039	-10000	0	-0.26	8	8
FADD	-0.088	0.27	-10000	0	-0.82	52	52
MAPK8	0.012	0.1	-10000	0	-0.47	3	3
TRAF2	0.008	0.07	-10000	0	-0.82	3	3
TRAILR3 (trimer)	-0.009	0.14	-10000	0	-0.8	12	12
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.078	0.19	-10000	0	-0.54	60	60
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.056	0.16	0.28	10	-0.44	56	66
JNK cascade	-0.032	0.14	-10000	0	-0.6	23	23
TRAIL (trimer)	-0.003	0.12	-10000	0	-0.79	9	9
TNFRSF10C	-0.009	0.14	-10000	0	-0.8	12	12
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.067	0.16	-10000	0	-0.47	60	60
TRAIL/TRAILR2/FADD	-0.077	0.19	-10000	0	-0.54	60	60
cell death	0.016	0.039	-10000	0	-0.25	8	8
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.005	0.11	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.014	0	-10000	0	-10000	0	0
CASP8	-0.001	0.023	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.066	0.16	-10000	0	-0.46	60	60

×

Signaling mediated by p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.1	0.28	-9999	-0.71	63	63
MKNK1	0.014	0	-9999	-10000	0	0
MAPK14	-0.043	0.12	-9999	-0.4	10	10
ATF2/c-Jun	-0.009	0.095	-9999	-10000	0	0
MAPK11	-0.043	0.12	-9999	-0.4	10	10
MITF	-0.048	0.17	-9999	-0.55	17	17
MAPKAPK5	-0.036	0.15	-9999	-0.49	10	10
KRT8	-0.11	0.23	-9999	-0.66	35	35
MAPKAPK3	0.014	0	-9999	-10000	0	0
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.062	0.18	-9999	-0.65	10	10
CEBPB	-0.036	0.15	-9999	-0.49	10	10
SLC9A1	-0.036	0.15	-9999	-0.49	10	10
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.03	0.15	-9999	-0.48	10	10
p38alpha-beta/MNK1	-0.037	0.15	-9999	-0.53	10	10
JUN	-0.008	0.095	-9999	-10000	0	0
PPARGC1A	-0.17	0.25	-9999	-0.7	50	50
USF1	-0.036	0.15	-9999	-0.49	10	10
RAB5/GDP/GDI1	-0.051	0.086	-9999	-0.36	10	10
NOS2	-0.12	0.32	-9999	-0.78	70	70
DDIT3	-0.045	0.16	-9999	-0.52	13	13
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.019	0.12	-9999	-0.4	10	10
p38alpha-beta/HBP1	-0.037	0.15	-9999	-0.53	10	10
CREB1	-0.033	0.15	-9999	-0.48	10	10
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.024	0.13	-9999	-0.47	10	10
RPS6KA4	-0.036	0.15	-9999	-0.49	10	10
PLA2G4A	-0.044	0.15	-9999	-0.52	14	14
GDI1	-0.036	0.15	-9999	-0.49	10	10
TP53	-0.052	0.18	-9999	-0.63	12	12
RPS6KA5	-0.039	0.15	-9999	-0.49	10	10
ESR1	-0.059	0.18	-9999	-0.57	21	21
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.043	0.15	-9999	-0.5	11	11
MEF2A	-0.036	0.15	-9999	-0.49	10	10
EIF4EBP1	-0.035	0.15	-9999	-0.48	10	10
KRT19	-0.18	0.23	-9999	-0.67	40	40
ELK4	-0.036	0.15	-9999	-0.49	10	10
ATF6	-0.036	0.15	-9999	-0.49	10	10
ATF1	-0.033	0.15	-9999	-0.48	10	10
p38alpha-beta/MAPKAPK2	-0.037	0.15	-9999	-0.53	10	10
p38alpha-beta/MAPKAPK3	-0.037	0.15	-9999	-0.53	10	10

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.12	0.28	-9999	-0.68	78	78
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.042	0.15	-9999	-0.43	57	57
IFNAR2	0.013	0.007	-9999	-10000	0	0
AKT1	-0.001	0.071	-9999	-0.59	1	1
ER alpha/Oestrogen	-0.026	0.14	-9999	-0.57	25	25
NFX1/SIN3/HDAC complex	0.042	0.026	-9999	-10000	0	0
EGF	-0.099	0.24	-9999	-0.6	77	77
SMG5	0.014	0	-9999	-10000	0	0
SMG6	0.014	0	-9999	-10000	0	0
SP3/HDAC2	0.019	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.14	0.25	-9999	-0.63	78	78
SAP18	0.012	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.18	0.34	-9999	-0.82	95	95
WRN	0.014	0	-9999	-10000	0	0
SP1	0.014	0.007	-9999	-10000	0	0
SP3	0.012	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.12	0.22	-9999	-0.62	40	40
Mad/Max	0.014	0.045	-9999	-0.43	4	4
TERT	-0.12	0.29	-9999	-0.7	78	78
CCND1	-0.11	0.27	-9999	-0.69	45	45
MAX	0.012	0.006	-9999	-10000	0	0
RBBP7	0.012	0.005	-9999	-10000	0	0
RBBP4	0.009	0.042	-9999	-0.59	2	2
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.012	0.004	-9999	-10000	0	0
Telomerase/911	0.027	0.041	-9999	-10000	0	0
CDKN1B	-0.08	0.23	-9999	-0.52	88	88
RAD1	0.014	0	-9999	-10000	0	0
XRCC5	0.014	0	-9999	-10000	0	0
XRCC6	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.005	-9999	-10000	0	0
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.012	0.006	-9999	-10000	0	0
JUN	0.012	0.006	-9999	-10000	0	0
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.01	0.006	-9999	-10000	0	0
FOS	-0.069	0.21	-9999	-0.59	57	57
IFN-gamma/IRF1	-0.13	0.25	-9999	-0.61	88	88
PARP2	0.014	0	-9999	-10000	0	0
BLM	0.01	0.057	-9999	-0.82	2	2
Telomerase	0	0.1	-9999	-0.44	10	10
IRF1	0.016	0.008	-9999	-10000	0	0
ESR1	-0.032	0.18	-9999	-0.75	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.018	-9999	-0.38	1	1
ubiquitin-dependent protein catabolic process	0.046	0.028	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.046	0.028	-9999	-10000	0	0
HDAC1	0.012	0.004	-9999	-10000	0	0
HDAC2	0.013	0.007	-9999	-10000	0	0
ATM	-0.001	0.022	-9999	-0.44	1	1
SMAD3	0.023	0.039	-9999	-0.53	2	2
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.006	0.059	-9999	-0.6	4	4
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.012	0.04	-9999	-0.82	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.12	0.24	-9999	-0.67	41	41
NR2F2	0.014	0.041	-9999	-0.8	1	1
MAPK3	0.013	0.032	-9999	-0.62	1	1
MAPK1	0.013	0.032	-9999	-0.62	1	1
TGFB1/TGF beta receptor Type II	0.012	0.04	-9999	-0.82	1	1
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.022	-9999	-0.44	1	1
NBN	0.014	0	-9999	-10000	0	0
EGFR	-0.018	0.15	-9999	-0.79	16	16
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.1	0.2	-9999	-0.47	92	92
MYC	0.012	0.006	-9999	-10000	0	0
IL2	0.002	0.042	-9999	-0.81	1	1
KU	0	0	-9999	-10000	0	0
RAD50	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
TGFB1	0.012	0.04	-9999	-0.82	1	1
TRF2/BLM	-0.003	0.041	-9999	-0.59	2	2
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.13	0.25	-9999	-0.66	61	61
SP1/HDAC2	0.021	0.014	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.12	0.22	-9999	-0.62	40	40
Smad3/Myc	0.027	0.034	-9999	-0.45	2	2
911 complex	-0.001	0.026	-9999	-0.54	1	1
IFNG	-0.16	0.33	-9999	-0.81	88	88
Telomerase/PinX1	-0.12	0.22	-9999	-0.62	40	40
Telomerase/AKT1/mTOR/p70S6K	0.005	0.075	-9999	-0.4	1	1
SIN3B	0.012	0.005	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.12	0.22	-9999	-0.64	35	35
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.12	0.22	-9999	-0.62	40	40
E2F1	-0.038	0.2	-9999	-0.83	26	26
ZNFX1	0.012	0.004	-9999	-10000	0	0
PIF1	-0.028	0.18	-9999	-0.82	21	21
NCL	0.014	0	-9999	-10000	0	0
DKC1	0.014	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.04	-9999	-0.82	1	1
EGFR	-0.017	0.15	-9999	-0.79	16	16
EGF/EGFR	-0.074	0.14	-9999	-0.48	20	20
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.07	0.14	-9999	-0.48	16	16
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.008	0.064	-9999	-0.74	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.098	0.24	-9999	-0.6	77	77
EGF/EGFR dimer/SHC	-0.085	0.17	-9999	-0.56	16	16
mol:GDP	-0.069	0.14	-9999	-0.47	16	16
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.009	0.051	-9999	-0.59	3	3
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.064	0.12	-9999	-0.7	1	1
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.065	0.13	-9999	-0.7	1	1
FRAP1	-0.035	0.15	-9999	-0.46	16	16
EGF/EGFR dimer	-0.1	0.2	-9999	-0.46	92	92
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.007	0.059	-9999	-0.49	6	6

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.034	0.12	-10000	0	-0.48	25	25
ER alpha/Gai/GDP/Gbeta gamma	0.02	0.097	-10000	0	-0.48	4	4
AKT1	0.01	0.13	-10000	0	-0.77	8	8
PIK3CA	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.008	0.13	-10000	0	-0.78	8	8
mol:Ca2+	-0.032	0.16	-10000	0	-0.58	7	7
IGF1R	0.012	0.04	-10000	0	-0.82	1	1
E2/ER alpha (dimer)/Striatin	-0.043	0.14	-10000	0	-0.45	40	40
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	-0.011	0.12	0.74	8	-10000	0	8
RhoA/GTP	-0.024	0.092	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.026	0.087	-10000	0	-0.51	3	3
regulation of stress fiber formation	-0.03	0.091	0.51	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.04	0.14	-10000	0	-0.51	33	33
KRAS	0.01	0.057	-10000	0	-0.82	2	2
G13/GTP	-0.027	0.11	-10000	0	-0.45	25	25
pseudopodium formation	0.03	0.091	-10000	0	-0.51	1	1
E2/ER alpha (dimer)/PELP1	-0.029	0.12	-10000	0	-0.49	25	25
GRB2	0.014	0	-10000	0	-10000	0	0
GNG2	0.014	0	-10000	0	-10000	0	0
GNAO1	0.006	0.075	-10000	0	-0.76	4	4
HRAS	0.012	0.04	-10000	0	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.022	0.11	-10000	0	-0.5	9	9
E2/ER beta (dimer)	-0.013	0.089	-10000	0	-0.61	9	9
mol:GDP	-0.032	0.11	-10000	0	-0.39	32	32
mol:NADP	0.022	0.11	-10000	0	-0.5	9	9
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
mol:IP3	-0.035	0.17	-10000	0	-0.61	7	7
IGF-1R heterotetramer	0.012	0.04	-10000	0	-0.82	1	1
PLCB1	-0.042	0.17	-10000	0	-0.4	69	69
PLCB2	-0.043	0.17	-10000	0	-0.4	70	70
IGF1	-0.077	0.22	-10000	0	-0.61	62	62
mol:L-citrulline	0.022	0.11	-10000	0	-0.5	9	9
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.014	0.064	-10000	0	-0.55	3	3
JNK cascade	-0.013	0.089	-10000	0	-0.61	9	9
BCAR1	0.014	0	-10000	0	-10000	0	0
ESR2	-0.004	0.12	-10000	0	-0.79	9	9
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.031	0.18	-10000	0	-0.74	25	25
Gq family/GDP/Gbeta gamma	-0.004	0.12	-10000	0	-0.68	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.027	0.064	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.026	0.087	-10000	0	-0.56	2	2
GNAZ	-0.015	0.15	-10000	0	-0.75	16	16
E2/ER alpha (dimer)	-0.034	0.14	-10000	0	-0.57	25	25
STRN	-0.009	0.12	-10000	0	-0.59	16	16
GNAL	-0.059	0.2	-10000	0	-0.59	51	51
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.009	0.079	-10000	0	-0.53	9	9
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.029	-10000	0	-0.59	1	1
HBEGF	-0.17	0.17	-10000	0	-0.46	85	85
cAMP biosynthetic process	-0.067	0.15	-10000	0	-0.49	27	27
SRC	0.027	0.093	-10000	0	-0.52	2	2
PI3K	-0.003	0.036	-10000	0	-0.43	3	3
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.028	0.095	-10000	0	-0.71	1	1
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.051	0.11	-10000	0	-0.51	6	6
Gs family/GTP	-0.068	0.15	-10000	0	-0.5	27	27
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.004	0.042	-10000	0	-0.5	3	3
vasodilation	0.022	0.1	-10000	0	-0.48	9	9
mol:DAG	-0.035	0.17	-10000	0	-0.61	7	7
Gs family/GDP/Gbeta gamma	-0.052	0.11	-10000	0	-0.57	5	5
MSN	0.03	0.097	-10000	0	-0.57	1	1
Gq family/GTP	-0.08	0.16	-10000	0	-0.43	69	69
mol:PI-3-4-5-P3	0.009	0.12	-10000	0	-0.75	8	8
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.022	0.1	0.48	9	-10000	0	9
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.029	0.099	-10000	0	-0.42	8	8
NOS3	0.021	0.11	-10000	0	-0.53	9	9
GNA11	0.009	0.051	-10000	0	-0.59	3	3
MAPKKK cascade	0.022	0.13	-10000	0	-0.57	10	10
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.093	-10000	0	-0.54	3	3
ruffle organization	0.03	0.091	-10000	0	-0.51	1	1
ROCK2	0.022	0.1	-10000	0	-0.64	1	1
GNA14	-0.083	0.22	-10000	0	-0.59	68	68
GNA15	0.011	0.041	-10000	0	-0.59	2	2
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.3	0.22	-10000	0	-0.64	30	30
MMP2	-0.04	0.18	-10000	0	-0.58	5	5

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.004	0.09	-10000	0	-0.82	5	5
ANTXR2	-0.006	0.13	-10000	0	-0.82	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.018	-10000	0	-0.1	14	14
monocyte activation	-0.026	0.11	-10000	0	-0.29	60	60
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	-0.018	0.069	-10000	0	-0.32	20	20
CYAA	-0.001	0.096	-10000	0	-0.51	14	14
MAP2K4	-0.003	0.015	-10000	0	-10000	0	0
IL1B	-0.036	0.15	-10000	0	-0.46	47	47
Channel	-0.018	0.099	-10000	0	-0.54	14	14
NLRP1	-0.004	0.028	-10000	0	-0.49	1	1
CALM1	0.014	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	0.1	14	-10000	0	14
MAPK3	-0.003	0.015	-10000	0	-10000	0	0
MAPK1	-0.003	0.015	-10000	0	-10000	0	0
PGR	-0.042	0.11	-10000	0	-0.35	48	48
PA/Cellular Receptors	-0.019	0.11	-10000	0	-0.58	14	14
apoptosis	-0.003	0.018	-10000	0	-0.1	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0	0.093	-10000	0	-0.49	14	14
macrophage activation	0.018	0.017	-10000	0	-10000	0	0
TNF	-0.025	0.17	-10000	0	-0.77	21	21
VCAM1	-0.026	0.11	-10000	0	-0.29	60	60
platelet activation	-0.004	0.022	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.025	-10000	0	-10000	0	0
IL18	0.004	0.064	-10000	0	-0.32	15	15
negative regulation of macrophage activation	-0.003	0.018	-10000	0	-0.1	14	14
LEF	-0.003	0.018	-10000	0	-0.1	14	14
CASP1	-0.003	0.019	-10000	0	-0.17	2	2
mol:cAMP	-0.004	0.022	-10000	0	-10000	0	0
necrosis	-0.003	0.018	-10000	0	-0.1	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.017	0.095	-10000	0	-0.52	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

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	-0.16	0.34	-9999	-0.82	90	90
alphaV beta3 Integrin	-0.032	0.13	-9999	-0.58	23	23
PTK2	-0.028	0.093	-9999	-0.46	10	10
positive regulation of JNK cascade	-0.013	0.052	-9999	-0.31	10	10
CDC42/GDP	0.039	0.085	-9999	-0.41	10	10
Rac1/GDP	0.041	0.084	-9999	-0.41	10	10
RAP1B	0.012	0.04	-9999	-0.82	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.012	0.029	-9999	-0.59	1	1
CDC42/GTP	-0.015	0.064	-9999	-0.38	10	10
nectin-3/I-afadin	-0.025	0.11	-9999	-0.53	20	20
RAPGEF1	0.036	0.093	-9999	-0.46	10	10
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.029	0.1	-9999	-0.53	10	10
PDGFB-D/PDGFRB	-0.16	0.34	-9999	-0.82	90	90
TLN1	0.023	0.06	-9999	-0.46	2	2
Rap1/GTP	-0.014	0.056	-9999	-0.38	3	3
IQGAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.024	-9999	-0.5	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.025	0.11	-9999	-0.53	20	20
PVR	0.012	0.04	-9999	-0.82	1	1
Necl-5(dimer)	0.012	0.04	-9999	-0.82	1	1
mol:GDP	0.036	0.1	-9999	-0.51	10	10
MLLT4	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.12	0.2	-9999	-0.47	99	99
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.029	-9999	-0.43	2	2
positive regulation of lamellipodium assembly	-0.017	0.058	-9999	-0.32	10	10
PVRL1	0.011	0.041	-9999	-0.59	2	2
PVRL3	-0.02	0.15	-9999	-0.7	20	20
PVRL2	0.014	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
CDH1	0.008	0.058	-9999	-0.59	4	4
CLDN1	-0.019	0.15	-9999	-0.68	20	20
JAM-A/CLDN1	-0.037	0.12	-9999	-0.5	19	19
SRC	-0.025	0.1	-9999	-0.6	10	10
ITGB3	-0.022	0.16	-9999	-0.74	20	20
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.029	-9999	-0.43	2	2
FARP2	0.033	0.098	-9999	-0.5	10	10
RAC1	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.022	0.1	-9999	-0.54	11	11
nectin-1/I-afadin	-0.002	0.029	-9999	-0.43	2	2
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	-0.023	0.1	-9999	-0.44	22	22
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.014	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.013	0.052	-9999	-0.31	10	10
alphaV/beta3 Integrin/Talin	0.013	0.12	-9999	-0.43	20	20
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	0.017	0.053	-9999	-0.36	1	1
VAV2	0.025	0.11	-9999	-0.51	10	10
RAP1/GDP	-0.015	0.065	-9999	-0.38	10	10
ITGAV	0.006	0.075	-9999	-0.76	4	4
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.021	0.097	-9999	-0.54	10	10
nectin-3(dimer)/I-afadin/I-afadin	-0.025	0.11	-9999	-0.53	20	20
Rac1/GTP	-0.02	0.07	-9999	-0.39	10	10
PTPRM	0.008	0.058	-9999	-0.27	11	11
E-cadherin/beta catenin/alpha catenin	-0.005	0.04	-9999	-0.57	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.018	0.086	-9999	-0.47	12	12
CRKL	0.012	0.04	-9999	-0.82	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.011	0.041	-9999	-0.59	2	2
ITGA4	-0.008	0.13	-9999	-0.82	11	11
alpha4/beta7 Integrin/MAdCAM1	-0.03	0.12	-9999	-0.49	25	25
EPO	-0.074	0.25	-9999	-0.82	44	44
alpha4/beta7 Integrin	-0.018	0.1	-9999	-0.6	13	13
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.018	0.1	-9999	-0.63	12	12
EPO/EPOR (dimer)	-0.077	0.21	-9999	-0.63	52	52
lamellipodium assembly	0	0.031	-9999	-0.35	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.003	0.036	-9999	-0.43	3	3
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.016	0.13	-9999	-0.52	3	3
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
MADCAM1	-0.018	0.15	-9999	-0.82	14	14
cell adhesion	-0.03	0.12	-9999	-0.49	25	25
CRKL/CBL	-0.001	0.03	-9999	-0.63	1	1
ITGB1	0.012	0.04	-9999	-0.82	1	1
SRC	-0.026	0.17	-9999	-0.51	44	44
ITGB7	0.011	0.041	-9999	-0.59	2	2
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.064	0.18	-9999	-0.56	44	44
p130Cas/Crk/Dock1	-0.001	0.15	-9999	-0.81	2	2
VCAM1	-0.063	0.24	-9999	-0.78	41	41
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.014	0.081	-9999	-0.49	12	12
BCAR1	-0.015	0.16	-9999	-0.47	44	44
EPOR	-0.002	0.11	-9999	-0.82	8	8
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0	0.031	-9999	-0.36	2	2

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.077	-9999	-0.6	7	7
PDGFRB	-0.16	0.34	-9999	-0.81	90	90
SPHK1	-0.023	0.05	-9999	-0.32	9	9
mol:S1P	-0.029	0.062	-9999	-0.42	6	6
S1P1/S1P/Gi	-0.015	0.13	-9999	-0.54	7	7
GNAO1	0.005	0.076	-9999	-0.77	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.077	0.2	-9999	-0.59	15	15
PLCG1	-0.015	0.13	-9999	-0.53	6	6
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.16	0.34	-9999	-0.81	90	90
GNAI2	0.012	0.005	-9999	-10000	0	0
GNAI3	0.012	0.006	-9999	-10000	0	0
GNAI1	0.01	0.03	-9999	-0.6	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.009	0.069	-9999	-0.52	7	7
S1P1/S1P	-0.04	0.078	-9999	-0.44	10	10
negative regulation of cAMP metabolic process	-0.014	0.13	-9999	-0.52	7	7
MAPK3	-0.022	0.17	-9999	-0.6	8	8
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	0.05	-9999	-0.7	2	2
PLCB2	-0.002	0.092	-9999	-0.43	7	7
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.032	0.066	-9999	-0.4	6	6
receptor internalization	-0.038	0.074	-9999	-0.41	10	10
PTGS2	-0.048	0.24	-9999	-0.6	63	63
Rac1/GTP	-0.032	0.066	-9999	-0.4	6	6
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	0.003	0.09	-9999	-0.82	5	5
negative regulation of T cell proliferation	-0.014	0.13	-9999	-0.52	7	7
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.017	0.15	-9999	-0.75	16	16
MAPK1	-0.022	0.17	-9999	-0.6	8	8
S1P1/S1P/PDGFB-D/PDGFRB	-0.071	0.19	-9999	-0.59	14	14
ABCC1	0.007	0.07	-9999	-0.82	3	3

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0	-10000	0	-10000	0	0
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	0.012	0.029	-10000	0	-0.59	1	1
Cbp/p300/PCAF	-0.018	0.082	-10000	0	-0.69	1	1
EP300	0.011	0.041	-10000	0	-0.59	2	2
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.007	0.1	-10000	0	-0.49	8	8
KAT2B	-0.015	0.13	-10000	0	-0.59	20	20
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.027	0.11	0.2	44	-0.28	26	70
RAR alpha/9cRA/Cyclin H	-0.022	0.058	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.001	0.11	-10000	0	-0.39	17	17
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.021	0.084	-10000	0	-0.48	7	7
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.021	-10000	0	-0.44	1	1
RXRs/RARs/NRIP1/9cRA	0.003	0.14	-10000	0	-0.51	6	6
NCOA2	-0.023	0.14	-10000	0	-0.59	26	26
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.012	0.029	-10000	0	-0.59	1	1
RARG	0.013	0.029	-10000	0	-0.59	1	1
RAR gamma1/9cRA	-0.001	0.018	-10000	0	-0.36	1	1
MAPK3	0.014	0.001	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.005	0.077	-10000	0	-0.59	7	7
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.043	0.1	-10000	0	-0.41	7	7
RARA	-0.001	0.086	-10000	0	-0.25	3	3
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.017	0.16	-10000	0	-0.53	25	25
PRKCA	0.015	0.04	-10000	0	-0.81	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.013	0.14	-10000	0	-0.52	5	5
RXRG	-0.053	0.17	-10000	0	-0.38	86	86
RXRA	0.009	0.08	-10000	0	-10000	0	0
RXRB	-0.011	0.12	-10000	0	-0.35	45	45
VDR/Vit D3/DNA	-0.001	0.021	-10000	0	-0.44	1	1
RBP1	-0.17	0.34	-10000	0	-0.81	92	92
CRBP1/9-cic-RA	-0.14	0.26	-10000	0	-0.63	92	92
RARB	-0.039	0.18	-10000	0	-0.6	38	38
PRKCG	-0.073	0.25	-10000	0	-0.81	44	44
MNAT1	0.014	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.018	0.14	-10000	0	-0.48	4	4
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.008	0.13	-10000	0	-0.5	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.002	0.11	-10000	0	-0.41	16	16
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.013	0.14	-10000	0	-0.52	5	5
positive regulation of DNA binding	-0.021	0.055	-10000	0	-10000	0	0
NRIP1	-0.011	0.14	-10000	0	-1.2	1	1
RXRs/RARs	-0.02	0.14	-10000	0	-0.43	16	16
RXRs/RXRs/DNA/9cRA	-0.045	0.1	-10000	0	-0.43	6	6
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.015	0.041	-10000	0	-10000	0	0
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.001	0.013	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.006	0.08	-10000	0	-0.82	4	4
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	-0.12	0.31	-10000	0	-0.82	69	69
CDKN1A	0.03	0.031	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.009	0.074	-10000	0	-0.63	6	6
mol:Ca2+	-0.076	0.18	0.38	5	-0.45	76	81
AGT	-0.096	0.24	-10000	0	-0.6	76	76
CCNA2	0.032	0.073	-10000	0	-0.75	1	1
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	0.008	0.088	-10000	0	-0.42	17	17
CDK2/Cyclin E1	0.037	0.054	-10000	0	-0.44	4	4
MAPK3	0.015	0.077	-10000	0	-0.63	6	6
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.077	-10000	0	-0.63	6	6
PTP4A1	0.026	0.068	-10000	0	-10000	0	0
PTP4A3	0.002	0.098	-10000	0	-0.82	6	6
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.014	0.083	-10000	0	-0.63	7	7
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.026	0.044	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.023	0.089	-10000	0	-10000	0	0
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.005	0.044	0.38	6	-10000	0	6
RHOC	0.026	0.044	-10000	0	-10000	0	0
RHOA	0.026	0.044	-10000	0	-10000	0	0
cell motility	0.031	0.046	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.031	0.063	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.11	0.24	-10000	0	-0.63	75	75
ROCK1	0.031	0.046	-10000	0	-10000	0	0
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0.014	0	-10000	0	-10000	0	0
mitosis	0.026	0.068	-10000	0	-10000	0	0
ATF5	0	0.11	-10000	0	-0.82	7	7

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.004	0.11	0.72	10	-10000	0	10
PI3K Class IB/PDE3B	-0.004	0.11	-10000	0	-0.72	10	10
PDE3B	-0.004	0.11	-10000	0	-0.73	10	10

×

Noncanonical Wnt signaling 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
NFATC2	-0.051	0.19	-9999	-0.6	45	45
GNB1/GNG2	-0.054	0.11	-9999	-0.53	8	8
mol:DAG	-0.003	0.12	-9999	-0.64	2	2
PLCG1	-0.004	0.12	-9999	-0.67	2	2
YES1	-0.021	0.14	-9999	-0.56	8	8
FZD3	0.006	0.065	-9999	-0.59	5	5
FZD6	0.014	0	-9999	-10000	0	0
G protein	-0.005	0.12	-9999	-0.68	2	2
MAP3K7	-0.046	0.16	-9999	-0.6	3	3
mol:Ca2+	-0.003	0.12	-9999	-0.61	2	2
mol:IP3	-0.003	0.12	-9999	-0.64	2	2
NLK	-0.003	0.006	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.059	0.17	-9999	-0.49	20	20
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.032	0.14	-9999	-0.6	8	8
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.021	0.14	-9999	-0.56	8	8
GO:0007205	-0.003	0.12	-9999	-0.62	2	2
WNT6	-0.043	0.2	-9999	-0.76	31	31
WNT4	-0.008	0.12	-9999	-0.66	14	14
NFAT1/CK1 alpha	-0.075	0.13	-9999	-0.52	17	17
GNG2	0.014	0	-9999	-10000	0	0
WNT5A	0.005	0.076	-9999	-0.68	5	5
WNT11	-0.076	0.25	-9999	-0.76	49	49
CDC42	-0.012	0.13	-9999	-0.52	8	8

×

Fc-epsilon receptor I signaling in mast cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.012	0.04	-9999	-0.82	1	1
LAT2	-0.049	0.13	-9999	-0.46	12	12
AP1	-0.09	0.12	-9999	-0.54	9	9
mol:PIP3	-0.065	0.18	-9999	-0.57	14	14
IKBKB	-0.023	0.11	-9999	-0.34	4	4
AKT1	-0.052	0.16	-9999	-0.63	6	6
IKBKG	-0.023	0.11	-9999	-0.34	4	4
MS4A2	-0.009	0.12	-9999	-0.65	13	13
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
MAP3K1	-0.013	0.11	-9999	-0.43	2	2
mol:Ca2+	-0.046	0.14	-9999	-0.41	14	14
LYN	0.012	0.03	-9999	-0.61	1	1
CBLB	-0.048	0.13	-9999	-0.46	12	12
SHC1	0.014	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.02	0.078	-9999	-0.32	26	26
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.011	0.041	-9999	-0.59	2	2
PLD2	-0.088	0.18	-9999	-0.68	10	10
PTPN13	-0.043	0.13	-9999	-0.47	11	11
PTPN11	0.01	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.02	0.13	-9999	-0.39	3	3
SYK	0.011	0.042	-9999	-0.6	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.15	-9999	-0.59	15	15
LAT	-0.059	0.15	-9999	-0.55	19	19
PAK2	-0.024	0.12	-9999	-0.47	3	3
NFATC2	-0.11	0.21	-9999	-0.67	45	45
HRAS	-0.034	0.13	-9999	-0.45	12	12
GAB2	0.011	0.041	-9999	-0.59	2	2
PLA2G1B	0.035	0.019	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.2	-9999	-0.62	21	21
Antigen/IgE/Fc epsilon R1	-0.14	0.19	-9999	-0.57	21	21
mol:GDP	-0.041	0.13	-9999	-0.47	12	12
JUN	0.014	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
FOS	-0.068	0.21	-9999	-0.59	57	57
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.084	0.12	-9999	-0.46	16	16
CHUK	-0.023	0.11	-9999	-0.34	4	4
KLRG1	-0.057	0.14	-9999	-0.45	18	18
VAV1	-0.053	0.14	-9999	-0.48	15	15
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.048	0.13	-9999	-0.46	12	12
negative regulation of mast cell degranulation	-0.047	0.13	-9999	-0.44	10	10
BTK	-0.045	0.13	-9999	-0.46	12	12
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.08	0.17	-9999	-0.63	15	15
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.68	7	7
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.066	0.15	-9999	-0.56	11	11
RAF1	0.023	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.18	-9999	-0.65	15	15
FCER1G	-0.004	0.11	-9999	-0.82	8	8
FCER1A	-0.2	0.29	-9999	-0.6	148	148
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.18	-9999	-0.63	16	16
MAPK3	0.034	0.019	-9999	-10000	0	0
MAPK1	0.034	0.019	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.001	0.1	-9999	-0.69	7	7
DUSP1	-0.022	0.14	-9999	-0.59	25	25
NF-kappa-B/RelA	-0.036	0.047	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.047	0.13	-9999	-0.45	12	12
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.068	0.1	-9999	-0.53	4	4
FER	-0.049	0.13	-9999	-0.46	13	13
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.033	0.079	-9999	-0.41	15	15
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.04	0.14	-9999	-0.47	13	13
cytokine secretion	-0.026	0.034	-9999	-10000	0	0
SPHK1	-0.058	0.15	-9999	-0.52	20	20
PTK2	-0.049	0.13	-9999	-0.47	12	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.15	-9999	-0.57	13	13
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.057	0.18	-9999	-0.53	12	12
MAP2K2	0.03	0.02	-9999	-10000	0	0
MAP2K1	0.03	0.02	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.08	0.11	-9999	-0.43	18	18
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.14	0.19	-9999	-0.63	21	21
mol:Choline	-0.087	0.18	-9999	-0.67	10	10
SHC/Grb2/SOS1	-0.067	0.097	-9999	-0.45	3	3
FYN	0.012	0.04	-9999	-0.82	1	1
DOK1	0.014	0	-9999	-10000	0	0
PXN	-0.038	0.12	-9999	-0.45	8	8
HCLS1	-0.05	0.13	-9999	-0.47	14	14
PRKCB	-0.045	0.14	-9999	-0.41	13	13
FCGR2B	0.005	0.071	-9999	-0.59	6	6
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.048	0.13	-9999	-0.45	10	10
LCP2	0.007	0.07	-9999	-0.82	3	3
PLA2G4A	-0.065	0.15	-9999	-0.49	25	25
RASA1	0.012	0.029	-9999	-0.59	1	1
mol:Phosphatidic acid	-0.087	0.18	-9999	-0.67	10	10
IKK complex	-0.002	0.09	-9999	-0.28	1	1
WIPF1	0.01	0.057	-9999	-0.82	2	2

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.049	0.18	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.012	0.04	-9999	-0.82	1	1
STAT1 (dimer)/Cbp/p300	-0.094	0.19	-9999	-0.73	18	18
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.014	0.03	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.07	0.09	-9999	-0.34	6	6
CaM/Ca2+	-0.078	0.15	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.066	0.23	-9999	-0.83	18	18
AKT1	-0.022	0.16	-9999	-10000	0	0
MAP2K1	-0.026	0.17	-9999	-10000	0	0
MAP3K11	-0.039	0.17	-9999	-10000	0	0
IFNGR1	0.007	0.016	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.22	-9999	-0.62	60	60
Rap1/GTP	-0.06	0.12	-9999	-10000	0	0
CRKL/C3G	-0.001	0.03	-9999	-0.63	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.092	0.18	-9999	-0.47	1	1
CEBPB	0.013	0.15	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.11	0.21	-9999	-0.92	10	10
STAT1	-0.065	0.23	-9999	-0.83	18	18
CALM1	0.014	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.16	0.33	-9999	-0.81	88	88
PIK3CA	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.054	0.22	-9999	-0.77	18	18
CEBPB/PTGES2/Cbp/p300	-0.037	0.07	-9999	-10000	0	0
mol:Ca2+	-0.084	0.16	-9999	-10000	0	0
MAPK3	-0.006	0.15	-9999	-10000	0	0
STAT1 (dimer)	-0.092	0.12	-9999	-0.48	6	6
MAPK1	-0.006	0.15	-9999	-10000	0	0
JAK2	0.006	0.033	-9999	-0.59	1	1
PIK3R1	0.009	0.051	-9999	-0.59	3	3
JAK1	0.007	0.016	-9999	-10000	0	0
CAMK2D	0.014	0	-9999	-10000	0	0
DAPK1	0.025	0.12	-9999	-0.58	5	5
SMAD7	0	0.074	-9999	-10000	0	0
CBL/CRKL/C3G	-0.071	0.14	-9999	-10000	0	0
PI3K	-0.077	0.15	-9999	-10000	0	0
IFNG	-0.16	0.33	-9999	-0.81	88	88
apoptosis	0.009	0.1	-9999	-0.45	4	4
CAMK2G	0.014	0	-9999	-10000	0	0
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.12	0.25	-9999	-0.6	90	90
CAMK2B	-0.14	0.27	-9999	-0.6	107	107
FRAP1	-0.019	0.15	-9999	-10000	0	0
PRKCD	-0.021	0.16	-9999	-10000	0	0
RAP1B	0.012	0.04	-9999	-0.82	1	1
negative regulation of cell growth	-0.07	0.09	-9999	-0.34	6	6
PTPN2	0.012	0.04	-9999	-0.82	1	1
EP300	0.011	0.041	-9999	-0.59	2	2
IRF1	-0.019	0.19	-9999	-0.53	27	27
STAT1 (dimer)/PIASy	-0.092	0.2	-9999	-0.77	18	18
SOCS1	-0.031	0.16	-9999	-0.66	25	25
mol:GDP	-0.069	0.13	-9999	-10000	0	0
CASP1	-0.001	0.076	-9999	-0.34	1	1
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.037	0.057	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.075	0.14	-9999	-10000	0	0
RAP1/GDP	-0.06	0.12	-9999	-10000	0	0
CBL	-0.039	0.17	-9999	-10000	0	0
MAP3K1	-0.038	0.17	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PIAS4	0.014	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.07	0.09	-9999	-0.34	6	6
PTPN11	-0.05	0.18	-9999	-10000	0	0
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.007	0.04	0.26	4	-10000	0	4
RFC1	0.007	0.04	0.25	7	-10000	0	7
PRKDC	0.007	0.04	0.25	8	-10000	0	8
RIPK1	0.014	0.003	-10000	0	-10000	0	0
CASP7	-0.013	0.04	0.23	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.054	0.12	-10000	0	-0.38	11	11
MAP2K4	-0.008	0.13	-10000	0	-0.43	10	10
mol:ceramide	-0.028	0.14	-10000	0	-0.48	11	11
GSN	0.007	0.04	0.26	5	-10000	0	5
FASLG/FAS/FADD/FAF1/Caspase 8	-0.025	0.12	-10000	0	-0.45	7	7
FAS	0.012	0.03	-10000	0	-0.59	1	1
BID	0.003	0.042	0.3	1	-0.56	1	2
MAP3K1	0.007	0.079	-10000	0	-10000	0	0
MAP3K7	0.013	0.004	-10000	0	-10000	0	0
RB1	0.006	0.047	0.26	5	-0.35	2	7
CFLAR	0.014	0.003	-10000	0	-10000	0	0
HGF/MET	-0.027	0.1	-10000	0	-0.54	8	8
ARHGDIB	0.007	0.04	-10000	0	-10000	0	0
FADD	-0.089	0.27	-10000	0	-0.82	52	52
actin filament polymerization	-0.007	0.04	-10000	0	-0.26	5	5
NFKB1	-0.032	0.063	-10000	0	-10000	0	0
MAPK8	-0.017	0.17	-10000	0	-0.45	35	35
DFFA	0.007	0.04	0.26	5	-10000	0	5
DNA fragmentation during apoptosis	0.007	0.043	0.26	4	-0.35	1	5
FAS/FADD/MET	-0.072	0.19	-10000	0	-0.56	54	54
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.001	0.1	-10000	0	-0.78	7	7
FAF1	0.014	0.005	-10000	0	-10000	0	0
PARP1	0.007	0.04	0.26	4	-10000	0	4
DFFB	0.007	0.043	0.26	4	-0.35	1	5
CHUK	-0.027	0.055	-10000	0	-10000	0	0
FASLG	-0.048	0.21	-10000	0	-0.75	34	34
FAS/FADD	-0.078	0.21	-10000	0	-0.63	52	52
HGF	-0.012	0.13	-10000	0	-0.66	16	16
LMNA	0.007	0.036	-10000	0	-10000	0	0
CASP6	0.007	0.04	0.26	4	-10000	0	4
CASP10	0.013	0.004	-10000	0	-10000	0	0
CASP3	0.009	0.047	0.3	8	-10000	0	8
PTPN13	0.002	0.082	-10000	0	-0.59	8	8
CASP8	0.006	0.048	0.38	7	-10000	0	7
IL6	-0.093	0.37	-10000	0	-1.1	43	43
MET	0.006	0.075	-10000	0	-0.76	4	4
ICAD/CAD	0.006	0.041	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.028	0.14	-10000	0	-0.49	11	11
activation of caspase activity by cytochrome c	0.003	0.041	0.3	1	-0.55	1	2
PAK2	0.007	0.039	0.26	4	-10000	0	4
BCL2	0	0.099	-10000	0	-0.7	8	8

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.004	0.21	-9999	-0.71	1	1
CRP	-0.026	0.25	-9999	-0.75	17	17
cell cycle arrest	-0.015	0.23	-9999	-0.73	7	7
TIMP1	0.003	0.2	-9999	-0.77	5	5
IL6ST	-0.042	0.18	-9999	-0.59	41	41
Rac1/GDP	-0.002	0.15	-9999	-0.57	13	13
AP1	0.007	0.13	-9999	-0.63	2	2
GAB2	0.011	0.041	-9999	-0.59	2	2
TNFSF11	-0.072	0.3	-9999	-0.73	27	27
HSP90B1	0.032	0.05	-9999	-10000	0	0
GAB1	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.009	0.15	-9999	-0.57	14	14
AKT1	0.058	0.03	-9999	-10000	0	0
FOXO1	0.064	0.029	-9999	-10000	0	0
MAP2K6	-0.02	0.16	-9999	-0.58	16	16
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	0.008	0.17	-9999	-0.57	10	10
MITF	-0.018	0.16	-9999	-0.56	18	18
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0.04	-9999	-0.82	1	1
A2M	0.021	0.034	-9999	-0.66	1	1
CEBPB	0.02	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.018	0.072	-9999	-0.38	2	2
STAT3	-0.015	0.24	-9999	-0.77	7	7
STAT1	-0.024	0.089	-9999	-0.35	27	27
CEBPD	-0.004	0.21	-9999	-0.65	4	4
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	0.02	0.038	-9999	-0.42	3	3
JUN	0.013	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.01	0.16	-9999	-0.53	18	18
MAPK11	-0.009	0.15	-9999	-0.57	14	14
STAT3 (dimer)/FOXO1	0.04	0.2	-9999	-10000	0	0
GRB2/SOS1/GAB family	-0.044	0.1	-9999	-0.54	8	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.016	0.15	-9999	-0.59	13	13
GRB2	0.014	0.001	-9999	-10000	0	0
JAK2	0.012	0.029	-9999	-0.59	1	1
LBP	-0.095	0.36	-9999	-0.9	57	57
PIK3R1	0.011	0.051	-9999	-0.59	3	3
JAK1	0.016	0.004	-9999	-10000	0	0
MYC	-0.004	0.21	-9999	-0.67	2	2
FGG	-0.033	0.26	-9999	-0.76	21	21
macrophage differentiation	-0.015	0.23	-9999	-0.73	7	7
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.059	0.15	-9999	-0.54	22	22
JUNB	-0.004	0.2	-9999	-0.65	2	2
FOS	-0.068	0.21	-9999	-0.59	57	57
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.019	0.16	-9999	-0.54	18	18
STAT1/PIAS1	-0.017	0.15	-9999	-0.54	12	12
GRB2/SOS1/GAB family/SHP2/PI3K	0.04	0.036	-9999	-10000	0	0
STAT3 (dimer)	-0.014	0.23	-9999	-0.76	7	7
PRKCD	0.017	0.18	-9999	-0.64	5	5
IL6R	0.007	0.072	-9999	-0.59	6	6
SOCS3	-0.004	0.15	-9999	-0.78	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	-0.006	0.12	-9999	-0.37	7	7
Rac1/GTP	-0.008	0.16	-9999	-0.57	13	13
HCK	0.006	0.07	-9999	-0.7	4	4
MAPKKK cascade	0.033	0.067	-9999	-0.54	2	2
bone resorption	-0.066	0.29	-9999	-0.69	27	27
IRF1	-0.004	0.21	-9999	-0.71	1	1
mol:GDP	-0.012	0.16	-9999	-0.58	15	15
SOS1	0.013	0.004	-9999	-10000	0	0
VAV1	-0.013	0.16	-9999	-0.59	15	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.013	0.15	-9999	-0.65	13	13
PTPN11	-0.001	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.035	0.16	-9999	-0.47	48	48
gp130 (dimer)/TYK2/TYK2/LMO4	-0.012	0.12	-9999	-0.4	14	14
gp130 (dimer)/JAK2/JAK2/LMO4	-0.011	0.12	-9999	-0.4	10	10
IL6	-0.05	0.2	-9999	-0.64	43	43
PIAS3	0.014	0	-9999	-10000	0	0
PTPRE	0.01	0.012	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
RAC1	0.014	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.031	0.15	-9999	-0.55	17	17
LMO4	0.016	0.011	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.16	-9999	-0.75	6	6
MCL1	0.063	0.028	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.035	0.18	-9999	-0.85	16	16
MAP4K1	-0.006	0.12	-9999	-0.76	11	11
MAP3K8	0.011	0.041	-9999	-0.59	2	2
PRKCB	-0.001	0.11	-9999	-0.76	8	8
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.012	0.04	-9999	-0.82	1	1
MAP3K1	0.03	0.1	-9999	-0.57	9	9
JUN	0.022	0.1	-9999	-0.52	13	13
MAP3K7	0.03	0.1	-9999	-0.57	9	9
GRAP2	-0.003	0.11	-9999	-0.7	10	10
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0.038	0.1	-9999	-0.54	9	9
LAT	-0.006	0.13	-9999	-0.82	10	10
LCP2	0.008	0.07	-9999	-0.82	3	3
MAPK8	0.014	0.11	-9999	-0.56	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.022	0.11	-9999	-0.61	9	9
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.033	0.18	-9999	-0.8	16	16

×

Arf6 downstream 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.008	0.16	-10000	0	-0.65	23	23
regulation of axonogenesis	-0.022	0.034	-10000	0	-10000	0	0
myoblast fusion	0.005	0.083	0.32	23	-10000	0	23
mol:GTP	-0.013	0.044	-10000	0	-0.19	23	23
regulation of calcium-dependent cell-cell adhesion	-0.019	0.065	0.37	6	-10000	0	6
ARF1/GTP	-0.008	0.03	-10000	0	-10000	0	0
mol:GM1	0.001	0.036	-10000	0	-0.19	2	2
mol:Choline	0.021	0.036	-10000	0	-0.37	1	1
lamellipodium assembly	-0.023	0.077	-10000	0	-0.32	23	23
MAPK3	0.014	0.067	-10000	0	-0.3	2	2
ARF6/GTP/NME1/Tiam1	0.019	0.066	-10000	0	-0.37	6	6
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	-0.005	0.083	-10000	0	-0.32	23	23
ARF1/GDP	0.006	0.077	-10000	0	-0.5	2	2
ARF6	0.006	0.025	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.008	0.065	-10000	0	-0.59	5	5
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.067	-10000	0	-0.3	2	2
actin filament bundle formation	0.021	0.068	0.49	2	-10000	0	2
KALRN	-0.035	0.1	-10000	0	-0.34	30	30
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.021	0.069	-10000	0	-0.5	2	2
NME1	0.013	0.04	-10000	0	-0.81	1	1
Rac1/GDP	-0.021	0.069	-10000	0	-0.5	2	2
substrate adhesion-dependent cell spreading	-0.013	0.044	-10000	0	-0.19	23	23
cortical actin cytoskeleton organization	-0.023	0.078	-10000	0	-0.32	23	23
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.013	0.044	-10000	0	-0.19	23	23
ARF6/GTP	-0.013	0.044	-10000	0	-0.19	23	23
RhoA/GTP	-0.008	0.03	-10000	0	-10000	0	0
mol:GDP	-0.023	0.078	-10000	0	-0.32	23	23
ARF6/GTP/RAB11FIP3/RAB11A	-0.005	0.024	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	0.012	0.042	-10000	0	-0.43	1	1
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.023	0.077	-10000	0	-0.32	23	23
ruffle organization	0.022	0.034	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.013	0.044	-10000	0	-0.19	23	23
PLD2	0.012	0.036	-10000	0	-10000	0	0
PIP5K1A	0.022	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.036	-10000	0	-0.37	1	1
Rac1/GTP	-0.024	0.078	-10000	0	-0.32	23	23

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.043	0.099	-10000	0	-0.65	4	4
UGCG	-0.002	0.1	-10000	0	-0.62	11	11
AKT1/mTOR/p70S6K/Hsp90/TERT	0.02	0.12	-10000	0	-0.42	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.006	0.1	-10000	0	-0.61	11	11
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.023	0.079	-10000	0	-0.45	8	8
FRAP1	0.053	0.12	-10000	0	-0.53	8	8
FOXO3	0.061	0.11	-10000	0	-0.57	3	3
AKT1	0.055	0.11	-10000	0	-0.55	5	5
GAB2	0.012	0.042	-10000	0	-0.59	2	2
SMPD1	0.014	0.026	-10000	0	-10000	0	0
SGMS1	0.014	0.026	-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	0.021	0.033	-10000	0	-0.36	3	3
CALM1	0.014	0	-10000	0	-10000	0	0
cell proliferation	0.033	0.073	-10000	0	-0.37	4	4
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.021	0.039	-10000	0	-0.43	3	3
RPS6KB1	0.006	0.07	-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	-0.005	0.13	-10000	0	-0.82	11	11
PIK3R1	0.013	0.051	-10000	0	-0.59	3	3
JAK1	0.017	0.002	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	0.061	0.098	-10000	0	-0.57	1	1
MYB	-0.11	0.39	-10000	0	-1.2	46	46
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.041	0.12	-10000	0	-0.57	8	8
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.064	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.042	0.12	-10000	0	-0.55	8	8
Rac1/GDP	0.026	0.031	-10000	0	-0.33	1	1
T cell proliferation	0.051	0.11	-10000	0	-0.61	4	4
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	-0.002	0.022	-10000	0	-0.066	46	46
PRKCZ	0.051	0.11	-10000	0	-0.64	4	4
NF kappa B1 p50/RelA	-0.021	0.078	-10000	0	-0.48	5	5
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.036	0.11	-10000	0	-0.63	6	6
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.066	0.24	-10000	0	-0.82	41	41
IL2RB	0.002	0.11	-10000	0	-0.79	8	8
TERT	-0.14	0.32	-10000	0	-0.82	78	78
E2F1	-0.033	0.15	-10000	0	-0.42	46	46
SOS1	0.014	0.002	-10000	0	-10000	0	0
RPS6	0.014	0	-10000	0	-10000	0	0
mol:cAMP	0.001	0.011	0.031	46	-10000	0	46
PTPN11	0.014	0.002	-10000	0	-10000	0	0
IL2RG	-0.01	0.15	-10000	0	-0.8	14	14
actin cytoskeleton organization	0.051	0.11	-10000	0	-0.61	4	4
GRB2	0.014	0.002	-10000	0	-10000	0	0
IL2	0.006	0.04	-10000	0	-0.82	1	1
PIK3CA	0.017	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.031	-10000	0	-0.31	1	1
LCK	-0.003	0.13	-10000	0	-0.81	10	10
BCL2	0.052	0.14	-10000	0	-0.74	9	9

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.16	0.34	-9999	-0.82	90	90
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.022	0.068	-9999	-0.52	2	2
GNAO1	0.008	0.076	-9999	-0.76	4	4
S1P/S1P3/G12/G13	-0.008	0.061	-9999	-0.51	5	5
AKT1	-0.056	0.1	-9999	-0.37	7	7
AKT3	0.037	0.1	-9999	-0.67	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.16	0.34	-9999	-0.82	90	90
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.014	0.029	-9999	-0.59	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.009	0.066	-9999	-0.66	4	4
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.031	0.081	-9999	-0.57	4	4
MAPK3	0.038	0.077	-9999	-0.54	4	4
MAPK1	0.038	0.077	-9999	-0.54	4	4
JAK2	0.034	0.099	-9999	-0.53	7	7
CXCR4	0.022	0.13	-9999	-0.56	16	16
FLT1	0.015	0.04	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.038	0.077	-9999	-0.54	4	4
S1P/S1P3/Gi	0.031	0.082	-9999	-0.58	4	4
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.063	-9999	-0.52	4	4
VEGFA	0.007	0.09	-9999	-0.81	5	5
S1P/S1P2/Gi	0.031	0.064	-9999	-0.53	2	2
VEGFR1 homodimer/VEGFA homodimer	0.02	0.084	-9999	-0.72	5	5
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.018	0.12	-9999	-0.61	4	4
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.014	0.15	-9999	-0.75	16	16
G12/G13	-0.006	0.061	-9999	-0.63	4	4
GNA14	-0.083	0.22	-9999	-0.59	68	68
GNA15	0.011	0.041	-9999	-0.59	2	2
GNA12	0.006	0.08	-9999	-0.82	4	4
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.051	-9999	-0.59	3	3
Rac1/GTP	-0.014	0.063	-9999	-0.52	4	4

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.037	0.099	-10000	0	-10000	0	0
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.041	0.11	-10000	0	-0.34	51	51
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.01	0.028	0.087	51	-10000	0	51
GNAL	-0.059	0.2	-10000	0	-0.59	51	51
GNG2	0.014	0	-10000	0	-10000	0	0
CRH	0.001	0.003	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.003	0.047	-10000	0	-0.36	7	7
MAPK11	0.009	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	0.15	0.31	-9999	-1.2	3	3
PLK1	0.081	0.086	-9999	-0.7	2	2
BIRC5	0.057	0.16	-9999	-0.61	19	19
HSPA1B	0.15	0.31	-9999	-1.2	3	3
MAP2K1	0.044	0.037	-9999	-10000	0	0
BRCA2	0.14	0.34	-9999	-1.3	6	6
FOXM1	0.14	0.36	-9999	-1.6	4	4
XRCC1	0.15	0.31	-9999	-1.2	3	3
FOXM1B/p19	-0.19	0.26	-9999	-1.1	11	11
Cyclin D1/CDK4	0.094	0.36	-9999	-1.1	6	6
CDC2	0.14	0.33	-9999	-1.2	4	4
TGFA	0.11	0.35	-9999	-1.2	5	5
SKP2	0.15	0.32	-9999	-1.2	3	3
CCNE1	0.012	0.08	-9999	-0.81	4	4
CKS1B	0.14	0.33	-9999	-1.3	5	5
RB1	-0.048	0.11	-9999	-0.83	3	3
FOXM1C/SP1	0.14	0.32	-9999	-1.4	4	4
AURKB	0.076	0.11	-9999	-0.68	5	5
CENPF	0.15	0.31	-9999	-1.2	3	3
CDK4	0.023	0.017	-9999	-10000	0	0
MYC	0.15	0.29	-9999	-1	3	3
CHEK2	0.044	0.037	-9999	-10000	0	0
ONECUT1	0.092	0.38	-9999	-1.1	9	9
CDKN2A	-0.35	0.39	-9999	-0.78	194	194
LAMA4	0.12	0.35	-9999	-1.2	5	5
FOXM1B/HNF6	0.086	0.41	-9999	-1.4	9	9
FOS	0.036	0.51	-9999	-1.2	36	36
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.13	0.33	-9999	-1.2	4	4
response to radiation	0.026	0.035	-9999	-10000	0	0
CENPB	0.15	0.31	-9999	-1.2	3	3
CENPA	0.14	0.32	-9999	-1.4	3	3
NEK2	0.14	0.32	-9999	-1.3	3	3
HIST1H2BA	0.14	0.31	-9999	-1.2	3	3
CCNA2	0.017	0.042	-9999	-0.83	1	1
EP300	0.011	0.041	-9999	-0.59	2	2
CCNB1/CDK1	0.14	0.34	-9999	-1.5	3	3
CCNB2	0.14	0.32	-9999	-1.4	3	3
CCNB1	0.15	0.33	-9999	-1.3	3	3
ETV5	0.14	0.32	-9999	-1.2	3	3
ESR1	0.12	0.36	-9999	-1.1	11	11
CCND1	0.098	0.37	-9999	-1.2	6	6
GSK3A	0.04	0.032	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.045	0.076	-9999	-0.53	5	5
CDK2	0.019	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.03	0.04	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.071	0.2	-9999	-1.2	5	5
GAS1	0.14	0.33	-9999	-1.2	7	7
MMP2	0.089	0.38	-9999	-1.1	7	7
RB1/FOXM1C	0.11	0.35	-9999	-1.3	4	4
CREBBP	0.014	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.001	0.16	-9999	-0.56	11	11
MAP3K8	0.01	0.042	-9999	-0.59	2	2
FOS	0.011	0.11	-9999	-0.47	10	10
PRKCA	0.011	0.041	-9999	-0.82	1	1
PTPN7	-0.017	0.16	-9999	-0.81	16	16
HRAS	0.011	0.04	-9999	-0.82	1	1
PRKCB	-0.002	0.11	-9999	-0.77	8	8
NRAS	0.013	0.001	-9999	-10000	0	0
RAS family/GTP	-0.004	0.042	-9999	-0.5	3	3
MAPK3	0.014	0.077	-9999	-0.38	7	7
MAP2K1	0.027	0.073	-9999	-0.39	9	9
ELK1	0.01	0.043	-9999	-0.85	1	1
BRAF	-0.011	0.055	-9999	-0.38	9	9
mol:GTP	-0.001	0.002	-9999	-0.006	55	55
MAPK1	0.014	0.077	-9999	-0.38	7	7
RAF1	-0.011	0.055	-9999	-0.38	9	9
KRAS	0.009	0.057	-9999	-0.82	2	2

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.004	-9999	-10000	0	0
CLOCK	0.012	0.058	-9999	-0.59	4	4
TIMELESS/CRY2	0.046	0.012	-9999	-10000	0	0
DEC1/BMAL1	-0.11	0.24	-9999	-0.62	75	75
ATR	0.014	0	-9999	-10000	0	0
NR1D1	0.045	0.014	-9999	-10000	0	0
ARNTL	0.017	0	-9999	-10000	0	0
TIMELESS	0.045	0.014	-9999	-10000	0	0
NPAS2	0.01	0.065	-9999	-0.59	5	5
CRY2	0.014	0	-9999	-10000	0	0
mol:CO	-0.015	0	-9999	-10000	0	0
CHEK1	0.014	0	-9999	-10000	0	0
mol:HEME	0.015	0	-9999	-10000	0	0
PER1	0.014	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.038	0.061	-9999	-0.68	1	1
BMAL1/CLOCK	0.009	0.1	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.004	-9999	-10000	0	0
mol:NADPH	0.015	0	-9999	-10000	0	0
PER1/TIMELESS	0.046	0.012	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.14	0.32	-9999	-0.82	75	75

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.012	0.04	-9999	-0.82	1	1
ITGB7	0.011	0.041	-9999	-0.59	2	2
ITGA4	-0.008	0.13	-9999	-0.82	11	11
alpha4/beta7 Integrin	-0.018	0.1	-9999	-0.6	13	13
alpha4/beta1 Integrin	-0.018	0.1	-9999	-0.63	12	12

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.015	0.077	-10000	0	-0.63	6	6
MAP4K4	0.032	0.074	-10000	0	-0.42	4	4
BAG4	0.011	0.041	-10000	0	-0.59	2	2
PKC zeta/ceramide	-0.014	0.045	0.21	1	-0.37	1	2
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.15	-10000	0	-0.82	15	15
BAX	-0.002	0.022	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.009	-10000	0	-10000	0	0
BAD	-0.012	0.042	0.21	5	-10000	0	5
SMPD1	0.019	0.053	-10000	0	-0.25	2	2
RB1	-0.014	0.049	0.21	5	-0.37	2	7
FADD/Caspase 8	-0.014	0.17	-10000	0	-0.43	53	53
MAP2K4	-0.004	0.04	-10000	0	-10000	0	0
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.004	0.04	-10000	0	-10000	0	0
EGF	-0.098	0.24	-10000	0	-0.6	77	77
mol:ceramide	-0.023	0.045	0.22	5	-10000	0	5
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.015	0.077	-10000	0	-0.63	6	6
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.014	0.048	0.21	5	-0.36	2	7
cell proliferation	-0.044	0.093	-10000	0	-0.39	5	5
BID	0.022	0.052	-10000	0	-10000	0	0
MAP3K1	-0.012	0.042	0.22	2	-10000	0	2
EIF2A	0.002	0.049	-10000	0	-0.44	2	2
TRADD	0.014	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.009	0.038	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.038	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.013	0.041	0.19	5	-10000	0	5
FADD	-0.028	0.18	-10000	0	-0.47	55	55
KSR1	-0.012	0.042	0.23	1	-10000	0	1
MAPK8	-0.003	0.053	0.21	5	-0.26	8	13
PRKRA	-0.012	0.042	0.21	5	-10000	0	5
PDGFA	0.002	0.098	-10000	0	-0.82	6	6
TRAF2	0.008	0.07	-10000	0	-0.82	3	3
IGF1	-0.077	0.22	-10000	0	-0.61	62	62
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.023	0.045	0.22	5	-10000	0	5
CTSD	0.014	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.025	0.11	-10000	0	-0.42	5	5
PRKCD	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.029	-10000	0	-0.59	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.015	0.077	-10000	0	-0.63	6	6
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.025	0.078	-10000	0	-0.45	4	4
TNFR1A/BAG4/TNF-alpha	-0.027	0.11	-10000	0	-0.54	17	17
mol:Sphingosine-1-phosphate	0.015	0.077	-10000	0	-0.62	6	6
MAP2K1	0.004	0.038	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	-0.003	0.036	0.33	1	-10000	0	1
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.002	0.029	-10000	0	-0.43	2	2
EIF2AK2	-0.006	0.051	0.23	1	-0.47	2	3
TNF-alpha/TNFR1A/FAN	-0.025	0.11	-10000	0	-0.54	17	17
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.036	0.044	-10000	0	-10000	0	0
MAP2K2	0.004	0.038	-10000	0	-10000	0	0
SMPD3	0.003	0.098	-10000	0	-0.33	25	25
TNF	-0.025	0.17	-10000	0	-0.77	21	21
PKC zeta/PAR4	-0.001	0.021	-10000	0	-0.43	1	1
mol:PHOSPHOCHOLINE	0.031	0.098	0.23	80	-10000	0	80
NF kappa B1/RelA/I kappa B alpha	-0.001	0.014	-10000	0	-10000	0	0
AIFM1	-0.003	0.036	0.2	4	-10000	0	4
BCL2	0	0.099	-10000	0	-0.7	8	8

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.008	0.039	-9999	-0.66	1	1
VDR	0.012	0.029	-9999	-0.59	1	1
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.021	0.11	-9999	-0.44	2	2
RXRs/LXRs/DNA/Oxysterols	0.029	0.12	-9999	-0.51	2	2
MED1	0.012	0.04	-9999	-0.82	1	1
mol:9cRA	0.005	0.012	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.006	0.11	-9999	-0.51	3	3
RXRs/NUR77	-0.003	0.13	-9999	-0.5	6	6
RXRs/PPAR	-0.099	0.16	-9999	-0.51	17	17
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.021	-9999	-0.44	1	1
RARs/VDR/DNA/Vit D3	-0.028	0.088	-9999	-0.47	1	1
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	0.012	0.029	-9999	-0.59	1	1
RARs/RARs/DNA/9cRA	-0.028	0.089	-9999	-0.4	2	2
RARG	0.012	0.029	-9999	-0.59	1	1
RPS6KB1	0.013	0.036	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.006	0.11	-9999	-0.51	3	3
THRA	0.014	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.021	-9999	-0.44	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	0	0.12	-9999	-0.46	7	7
NR1H4	0.002	0.04	-9999	-0.82	1	1
RXRs/LXRs/DNA	0.021	0.12	-9999	-0.44	2	2
NR1H2	0.019	0.008	-9999	-10000	0	0
NR1H3	0.013	0.07	-9999	-0.81	3	3
RXRs/VDR/DNA/Vit D3	0.004	0.11	-9999	-0.45	5	5
NR4A1	-0.002	0.096	-9999	-0.59	11	11
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.006	0.084	-9999	-0.36	3	3
RXRG	-0.052	0.2	-9999	-0.61	47	47
RXR alpha/CCPG	0.024	0.006	-9999	-10000	0	0
RXRA	0.019	0.008	-9999	-10000	0	0
RXRB	0.019	0.01	-9999	-10000	0	0
THRB	-0.029	0.16	-9999	-0.59	30	30
PPARG	-0.23	0.3	-9999	-0.59	169	169
PPARD	0.014	0	-9999	-10000	0	0
TNF	0.015	0.19	-9999	-0.71	21	21
mol:Oxysterols	0.005	0.011	-9999	-10000	0	0
cholesterol transport	0.029	0.11	-9999	-0.5	2	2
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.041	0.18	-9999	-0.6	38	38
RXRs/NUR77/BCL2	-0.008	0.11	-9999	-0.52	1	1
SREBF1	0.037	0.11	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.001	0.12	-9999	-0.46	7	7
ABCA1	0.032	0.13	-9999	-0.91	3	3
RARs/THRs	-0.048	0.11	-9999	-0.56	4	4
RXRs/FXR	-0.001	0.12	-9999	-0.48	6	6
BCL2	0	0.099	-9999	-0.7	8	8

×

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

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
BAG4	0.011	0.041	-9999	-0.59	2	2
Caspase 8 (4 units)	-0.035	0.076	-9999	-0.46	3	3
NEF	-0.008	0.049	-9999	-10000	0	0
NFKBIA	0.013	0.023	-9999	-10000	0	0
BIRC3	0.02	0.15	-9999	-0.75	15	15
CYCS	0.006	0.11	-9999	-0.53	3	3
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.028	0.18	-9999	-0.87	17	17
MAP2K7	0.008	0.096	-9999	-0.44	2	2
protein ubiquitination	0.03	0.097	-9999	-0.44	2	2
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	0.012	0.029	-9999	-0.59	1	1
BID	-0.003	0.11	-9999	-0.51	5	5
NF-kappa-B/RelA/I kappa B alpha	-0.011	0.059	-9999	-10000	0	0
TRADD	0.014	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
CFLAR	0.014	0	-9999	-10000	0	0
FADD	-0.088	0.27	-9999	-0.82	52	52
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.011	0.06	-9999	-10000	0	0
MAPK8	0.012	0.1	-9999	-0.43	3	3
APAF1	0.012	0.029	-9999	-0.59	1	1
TRAF1	-0.006	0.13	-9999	-0.82	10	10
TRAF2	0.008	0.07	-9999	-0.82	3	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.011	0.11	-9999	-0.48	5	5
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.014	0.12	-9999	-0.57	3	3
CHUK	0.03	0.1	-9999	-0.49	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.057	0.15	-9999	-0.46	52	52
TCRz/NEF	-0.05	0.17	-9999	-0.51	42	42
TNF	-0.025	0.17	-9999	-0.77	21	21
FASLG	-0.05	0.26	-9999	-0.8	41	41
NFKB1	0.013	0.023	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.027	0.11	-9999	-0.54	17	17
CASP6	-0.021	0.047	-9999	-10000	0	0
CASP7	0.041	0.12	-9999	-0.51	3	3
RELA	0.013	0.023	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.041	0.12	-9999	-0.51	3	3
TNFRSF1A	0.014	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.002	0.029	-9999	-0.43	2	2
CASP8	0.014	0	-9999	-10000	0	0
CASP9	0.014	0	-9999	-10000	0	0
MAP3K14	0.022	0.11	-9999	-0.51	3	3
APAF-1/Caspase 9	-0.037	0.094	-9999	-0.5	4	4
BCL2	0.013	0.11	-9999	-0.46	4	4

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.03	0.031	-9999	-10000	0	0
epithelial cell differentiation	-0.003	0.032	-9999	-10000	0	0
CYFIP2	0.009	0.058	-9999	-0.67	3	3
ENAH	0.065	0.042	-9999	-10000	0	0
EGFR	-0.017	0.15	-9999	-0.79	16	16
EPHA2	0.005	0.071	-9999	-0.59	6	6
MYO6	0.037	0.037	-9999	-10000	0	0
CTNNB1	0.012	0.029	-9999	-0.59	1	1
ABI1/Sra1/Nap1	-0.003	0.036	-9999	-0.54	1	1
AQP5	-0.33	0.21	-9999	-0.46	305	305
CTNND1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.037	0.034	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.004	0.12	-9999	-0.44	23	23
EGF	-0.098	0.24	-9999	-0.6	77	77
NCKAP1	0.014	0	-9999	-10000	0	0
AQP3	-0.13	0.21	-9999	-0.71	4	4
cortical microtubule organization	-0.003	0.032	-9999	-10000	0	0
GO:0000145	0.036	0.032	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.032	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GDP	-0.007	0.042	-9999	-0.48	1	1
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.044	-9999	-0.49	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.049	0.034	-9999	-10000	0	0
PVRL2	0.014	0	-9999	-10000	0	0
ZYX	0.037	0.034	-9999	-10000	0	0
ARF6/GTP	-0.005	0.04	-9999	-0.45	1	1
CDH1	0.008	0.058	-9999	-0.59	4	4
EGFR/EGFR/EGF/EGF	-0.067	0.13	-9999	-0.61	3	3
RhoA/GDP	-0.003	0.029	-9999	-10000	0	0
actin cytoskeleton organization	0.042	0.039	-9999	-10000	0	0
IGF-1R heterotetramer	0.012	0.04	-9999	-0.82	1	1
GIT1	0.014	0	-9999	-10000	0	0
IGF1R	0.012	0.04	-9999	-0.82	1	1
IGF1	-0.077	0.22	-9999	-0.61	62	62
DIAPH1	-0.003	0.042	-9999	-0.58	2	2
Wnt receptor signaling pathway	0.003	0.032	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.007	0.042	-9999	-0.48	1	1
CTNNA1	0.014	0	-9999	-10000	0	0
VCL	0.043	0.039	-9999	-10000	0	0
EFNA1	0.012	0.04	-9999	-0.82	1	1
LPP	0.044	0.04	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.008	0.05	-9999	-0.55	1	1
SEC6/SEC8	-0.003	0.025	-9999	-10000	0	0
MGAT3	0.004	0.12	-9999	-0.44	23	23
HGF/MET	-0.019	0.083	-9999	-0.71	2	2
HGF	-0.012	0.13	-9999	-0.66	16	16
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.03	0.031	-9999	-10000	0	0
actin cable formation	0.083	0.039	-9999	-10000	0	0
KIAA1543	0.017	0.11	-9999	-0.66	5	5
KIFC3	0.037	0.034	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
EXOC3	0.014	0	-9999	-10000	0	0
ACTN1	0.036	0.041	-9999	-0.44	1	1
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.003	0.032	-9999	-10000	0	0
EXOC4	0.014	0	-9999	-10000	0	0
STX4	0.037	0.034	-9999	-10000	0	0
PIP5K1C	0.037	0.034	-9999	-10000	0	0
LIMA1	0.014	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
ROCK1	-0.006	0.037	-9999	-10000	0	0
adherens junction assembly	0.034	0.11	-9999	-0.64	5	5
IGF-1R heterotetramer/IGF1	-0.044	0.1	-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	0.006	0.075	-9999	-0.76	4	4
PLEKHA7	0.018	0.09	-9999	-0.58	3	3
mol:GTP	-0.006	0.044	-9999	-0.49	1	1
establishment of epithelial cell apical/basal polarity	0.064	0.031	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.03	0.031	-9999	-10000	0	0
regulation of cell-cell adhesion	0.042	0.039	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.03	0.031	-9999	-10000	0	0

×

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	0.014	0	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
CRKL	-0.021	0.12	-9999	-0.42	8	8
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.012	0.04	-9999	-0.82	1	1
IRS1/Crk	-0.021	0.12	-9999	-0.41	7	7
IGF-1R heterotetramer/IGF1/PTP1B	-0.052	0.12	-9999	-0.48	7	7
AKT1	0.004	0.11	-9999	-0.49	3	3
BAD	0.013	0.1	-9999	-0.47	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.02	0.12	-9999	-0.4	7	7
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.021	0.12	-9999	-0.41	7	7
RAF1	0.018	0.1	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.042	0.1	-9999	-0.54	1	1
YWHAZ	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.033	0.13	-9999	-0.33	63	63
PIK3CA	0.014	0	-9999	-10000	0	0
RPS6KB1	0.004	0.11	-9999	-0.49	3	3
GNB2L1	0.014	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.014	0.089	-9999	-0.38	2	2
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.037	0.091	-9999	-0.57	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.039	0.095	-9999	-10000	0	0
IGF-1R heterotetramer	0.001	0.048	-9999	-0.8	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.045	0.11	-9999	-0.41	7	7
Crk/p130 Cas/Paxillin	-0.039	0.094	-9999	-0.51	1	1
IGF1R	0.001	0.048	-9999	-0.8	1	1
IGF1	-0.079	0.22	-9999	-0.62	62	62
IRS2/Crk	-0.012	0.11	-9999	-0.53	1	1
PI3K	-0.044	0.11	-9999	-0.56	3	3
apoptosis	-0.02	0.093	-9999	-10000	0	0
HRAS/GDP	-0.001	0.031	-9999	-0.64	1	1
PRKCD	-0.015	0.15	-9999	-0.56	1	1
RAF1/14-3-3 E	0.025	0.09	-9999	-10000	0	0
BAD/14-3-3	0.02	0.097	-9999	-10000	0	0
PRKCZ	0.004	0.11	-9999	-0.49	3	3
Crk/p130 Cas/Paxillin/FAK1	-0.03	0.073	-9999	-10000	0	0
PTPN1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.025	0.15	-9999	-0.4	57	57
BCAR1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.046	0.11	-9999	-0.48	8	8
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
IRS1/NCK2	-0.021	0.12	-9999	-0.4	7	7
GRB10	0.01	0.057	-9999	-0.82	2	2
PTPN11	-0.02	0.12	-9999	-0.4	7	7
IRS1	-0.032	0.13	-9999	-0.33	63	63
IRS2	-0.022	0.12	-9999	-0.4	7	7
IGF-1R heterotetramer/IGF1	-0.068	0.16	-9999	-0.46	63	63
GRB2	0.014	0	-9999	-10000	0	0
PDPK1	-0.004	0.11	-9999	-0.53	3	3
YWHAE	0.014	0	-9999	-10000	0	0
PRKD1	-0.024	0.16	-9999	-0.52	10	10
SHC1	0.014	0	-9999	-10000	0	0

×

Aurora B signaling

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
Condensin I complex	0.032	0.046	-9999	-10000	0	0
STMN1	0.016	0.095	-9999	-0.7	7	7
Aurora B/RasGAP/Survivin	-0.005	0.14	-9999	-0.61	21	21
Chromosomal passenger complex/Cul3 protein complex	0.024	0.072	-9999	-0.4	7	7
BIRC5	-0.021	0.17	-9999	-0.81	19	19
DES	-0.31	0.27	-9999	-0.55	223	223
Aurora C/Aurora B/INCENP	0.013	0.082	-9999	-0.54	8	8
Aurora B/TACC1	0.009	0.064	-9999	-0.51	6	6
Aurora B/PP2A	0.011	0.07	-9999	-0.62	5	5
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.017	0.019	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.008	0.11	-9999	-0.63	13	13
Cul3 protein complex	-0.005	0.042	-9999	-10000	0	0
KIF2C	0.02	0.045	-9999	-0.38	3	3
PEBP1	0.014	0.002	-9999	-10000	0	0
KIF20A	0.013	0.001	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.01	0.074	-9999	-0.59	6	6
SEPT1	0.002	0.098	-9999	-0.82	6	6
SMC2	0.014	0	-9999	-10000	0	0
SMC4	0.012	0.04	-9999	-0.82	1	1
NSUN2/NPM1/Nucleolin	0.027	0.047	-9999	-0.38	4	4
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	0.017	0.042	-9999	-0.36	5	5
AURKB	0.011	0.091	-9999	-0.82	5	5
AURKC	0.005	0.081	-9999	-0.73	5	5
CDCA8	0.013	0.041	-9999	-0.83	1	1
cytokinesis	-0.02	0.082	-9999	-0.55	6	6
Aurora B/Septin1	0.009	0.1	-9999	-0.5	11	11
AURKA	-0.001	0.11	-9999	-0.82	7	7
INCENP	0.015	0.003	-9999	-10000	0	0
KLHL13	0.011	0.041	-9999	-0.59	2	2
BUB1	0.013	0.001	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.002	0.14	-9999	-0.57	20	20
EVI5	0.015	0.001	-9999	-10000	0	0
RhoA/GTP	-0.01	0.051	-9999	-0.42	5	5
SGOL1	0.014	0	-9999	-10000	0	0
CENPA	0.02	0.075	-9999	-0.47	7	7
NCAPG	0.014	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.011	0.07	-9999	-0.62	5	5
NCAPD2	0.008	0.07	-9999	-0.82	3	3
Aurora B/PP1-gamma	0.011	0.07	-9999	-0.62	5	5
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	0.008	0.07	-9999	-0.82	3	3
NPM1	0.007	0.048	-9999	-0.42	5	5
RASA1	0.012	0.029	-9999	-0.59	1	1
KLHL9	0.008	0.058	-9999	-0.59	4	4
mitotic prometaphase	0.001	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.07	-9999	-0.62	5	5
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.011	0.057	-9999	-0.46	5	5
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	0.007	0.048	-9999	-0.42	5	5
MYLK	0.011	0.068	-9999	-0.4	10	10
KIF23	0.014	0.002	-9999	-10000	0	0
VIM	0.014	0.094	-9999	-0.63	9	9
RACGAP1	0.014	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.007	0.048	-9999	-0.42	5	5
Chromosomal passenger complex	0.028	0.07	-9999	-0.49	5	5
Chromosomal passenger complex/EVI5	0.028	0.14	-9999	-0.55	20	20
TACC1	0.012	0.029	-9999	-0.59	1	1
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

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	0.014	0	-9999	-10000	0	0
SPHK1	-0.004	0.12	-9999	-0.82	9	9
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.016	0.051	-9999	-0.28	12	12
GNAO1	0.006	0.075	-9999	-0.76	4	4
mol:Sphinganine-1-P	0.011	0.094	-9999	-0.63	9	9
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.01	0.053	-9999	-0.45	4	4
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.006	0.061	-9999	-0.63	4	4
S1PR3	0.007	0.065	-9999	-0.65	4	4
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.007	0.041	-9999	-10000	0	0
S1PR5	0.012	0.029	-9999	-0.59	1	1
S1PR4	-0.025	0.17	-9999	-0.81	20	20
GNAI1	0.012	0.029	-9999	-0.59	1	1
S1P/S1P5/G12	-0.011	0.059	-9999	-0.48	4	4
S1P/S1P3/Gq	-0.013	0.12	-9999	-0.56	5	5
S1P/S1P4/Gi	0.017	0.093	-9999	-0.5	5	5
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.015	0.15	-9999	-0.75	16	16
GNA14	-0.083	0.22	-9999	-0.59	68	68
GNA15	0.011	0.041	-9999	-0.59	2	2
GNA12	0.006	0.08	-9999	-0.82	4	4
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.051	-9999	-0.59	3	3
ABCC1	0.008	0.07	-9999	-0.82	3	3

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0.04	-10000	0	-0.82	1	1
Rac1/GDP	0.002	0.012	-10000	0	-10000	0	0
DOCK1	0.011	0.041	-10000	0	-0.59	2	2
ITGA4	-0.008	0.13	-10000	0	-0.82	11	11
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.018	0.1	-10000	0	-0.6	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.015	0.09	-10000	0	-0.54	12	12
alpha4/beta7 Integrin/Paxillin	-0.014	0.081	-10000	0	-0.49	11	11
lamellipodium assembly	-0.002	0.044	-10000	0	-0.65	1	1
PIK3CA	0.014	0	-10000	0	-10000	0	0
PI3K	-0.003	0.036	-10000	0	-0.43	3	3
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.01	0.057	-10000	0	-0.82	2	2
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
ARF6/GTP	-0.012	0.069	-10000	0	-0.42	12	12
cell adhesion	-0.015	0.081	-10000	0	-0.45	14	14
CRKL/CBL	-0.001	0.03	-10000	0	-0.63	1	1
alpha4/beta1 Integrin/Paxillin	-0.014	0.081	-10000	0	-0.49	12	12
ITGB1	0.012	0.04	-10000	0	-0.82	1	1
ITGB7	0.011	0.041	-10000	0	-0.59	2	2
ARF6/GDP	0.002	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.055	0.15	-10000	0	-0.48	44	44
p130Cas/Crk/Dock1	-0.002	0.024	-10000	0	-10000	0	0
VCAM1	-0.063	0.24	-10000	0	-0.78	41	41
alpha4/beta1 Integrin/Paxillin/Talin	-0.015	0.082	-10000	0	-0.46	14	14
alpha4/beta1 Integrin/Paxillin/GIT1	-0.013	0.076	-10000	0	-0.46	12	12
BCAR1	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.075	0.45	12	-10000	0	12
CBL	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0	-10000	0	-10000	0	0
GIT1	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.015	0.082	-10000	0	-0.46	14	14
Rac1/GTP	-0.003	0.05	-10000	0	-0.75	1	1

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.043	0.11	-9999	-0.62	2	2
TC10/GTP	-0.039	0.094	-9999	-0.42	2	2
Insulin Receptor/Insulin/IRS1/Shp2	-0.004	0.039	-9999	-0.46	2	2
HRAS	0.012	0.04	-9999	-0.82	1	1
APS homodimer	0.01	0.057	-9999	-0.82	2	2
GRB14	-0.051	0.19	-9999	-0.63	42	42
FOXO3	-0.008	0.046	-9999	-0.64	2	2
AKT1	0.019	0.1	-9999	-0.5	1	1
INSR	0.015	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin	0.036	0.03	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0.057	-9999	-0.82	2	2
SORBS1	-0.072	0.21	-9999	-0.59	60	60
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.036	0.03	-9999	-10000	0	0
CAV1	-0.022	0.15	-9999	-0.48	42	42
CBL/APS/CAP/Crk-II/C3G	-0.043	0.1	-9999	-0.46	2	2
Insulin Receptor/Insulin/IRS1/NCK2	-0.004	0.039	-9999	-0.46	2	2
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.041	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.039	0.028	-9999	-10000	0	0
RPS6KB1	0.027	0.097	-9999	-10000	0	0
PARD6A	0.01	0.05	-9999	-0.7	2	2
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.009	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.026	0.076	-9999	-10000	0	0
HRAS/GTP	-0.005	0.037	-9999	-10000	0	0
Insulin Receptor	0.015	0.003	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.003	0.035	-9999	-10000	0	0
PRKCI	-0.007	0.021	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.033	0.094	-9999	-0.54	1	1
SHC1	0.014	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.017	-9999	-10000	0	0
PI3K	-0.005	0.041	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
RHOQ	0.014	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.001	0.031	-9999	-0.64	1	1
AKT2	0.019	0.1	-9999	-0.5	1	1
PRKCZ	-0.008	0.032	-9999	-0.49	1	1
SH2B2	0.01	0.057	-9999	-0.82	2	2
SHC/SHIP	0.031	0.043	-9999	-10000	0	0
F2RL2	-0.25	0.39	-9999	-0.81	136	136
TRIP10	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.002	0.032	-9999	-0.47	2	2
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.002	0.029	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.012	0.029	-9999	-0.59	1	1
NCK1	0.014	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.047	0.11	-9999	-0.49	2	2
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.005	0.047	-9999	-0.48	4	4
INPP5D	0.024	0.045	-9999	-0.43	2	2
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.006	0.063	-9999	-0.92	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.011	0.041	-9999	-0.59	2	2
p62DOK/RasGAP	0	0.017	-9999	-10000	0	0
INS	0	0.056	-9999	-0.81	2	2
mol:PI-3-4-P2	0.024	0.045	-9999	-0.42	2	2
GRB2	0.014	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.11	-9999	-0.62	1	1
PTPRA	0.015	0.003	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.034	0.028	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.039	-9999	-0.47	2	2
Insulin Receptor/Insulin/IRS3	-0.003	0.042	-9999	-0.62	2	2
Par3/Par6	-0.15	0.22	-9999	-0.47	135	135

×

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	0.032	0.042	-9999	-0.58	2	2
VEGFR1 homodimer/NRP1	-0.001	0.031	-9999	-0.63	1	1
mol:DAG	-0.054	0.2	-9999	-0.56	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.007	0.07	-9999	-0.6	5	5
CaM/Ca2+	-0.044	0.19	-9999	-0.53	1	1
HIF1A	0.021	0.016	-9999	-10000	0	0
GAB1	0.014	0	-9999	-10000	0	0
AKT1	-0.02	0.18	-9999	-0.69	3	3
PLCG1	-0.055	0.2	-9999	-0.57	1	1
NOS3	-0.016	0.17	-9999	-0.51	4	4
CBL	0.014	0	-9999	-10000	0	0
mol:NO	-0.014	0.17	-9999	-0.49	4	4
FLT1	0.031	0.036	-9999	-0.72	1	1
PGF	-0.14	0.32	-9999	-0.82	78	78
VEGFR1 homodimer/NRP2/VEGFR121	-0.009	0.076	-9999	-1	1	1
CALM1	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
eNOS/Hsp90	-0.006	0.16	-9999	-0.57	1	1
endothelial cell proliferation	-0.031	0.18	-9999	-10000	0	0
mol:Ca2+	-0.054	0.2	-9999	-0.56	1	1
MAPK3	-0.033	0.18	-9999	-10000	0	0
MAPK1	-0.033	0.18	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
PLGF homodimer	-0.14	0.32	-9999	-0.82	78	78
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.065	0.24	-9999	-0.82	40	40
VEGFA homodimer	0.004	0.089	-9999	-0.82	5	5
VEGFR1 homodimer/VEGFA homodimer	0.027	0.078	-9999	-0.65	5	5
platelet activating factor biosynthetic process	-0.024	0.18	-9999	-10000	0	0
PI3K	-0.086	0.18	-9999	-0.7	4	4
PRKCA	-0.043	0.19	-9999	-0.52	1	1
PRKCB	-0.051	0.2	-9999	-0.52	1	1
VEGFR1 homodimer/PLGF homodimer	-0.072	0.22	-9999	-0.54	79	79
VEGFA	0.004	0.09	-9999	-0.82	5	5
VEGFB	0.012	0.04	-9999	-0.82	1	1
mol:IP3	-0.054	0.2	-9999	-0.56	1	1
RASA1	0.04	0.043	-9999	-0.53	2	2
NRP2	0.01	0.057	-9999	-0.82	2	2
VEGFR1 homodimer	0.031	0.036	-9999	-0.72	1	1
VEGFB homodimer	0.012	0.04	-9999	-0.82	1	1
NCK1	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.048	0.21	-9999	-0.73	9	9
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.085	0.18	-9999	-0.69	4	4
mol:L-citrulline	-0.014	0.17	-9999	-0.49	4	4
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.007	0.065	-9999	-0.99	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.007	0.069	-9999	-1	1	1
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.081	0.17	-9999	-0.72	3	3
PDPK1	-0.036	0.19	-9999	-0.65	4	4
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.007	0.069	-9999	-1	1	1
mol:NADP	-0.014	0.17	-9999	-0.49	4	4
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.007	0.064	-9999	-0.97	1	1
VEGFR1 homodimer/NRP2	0.03	0.05	-9999	-0.56	3	3

×

p38 MAPK signaling 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
TRAF6/ASK1	-0.001	0.013	-9999	-0.27	1	1
TRAF2/ASK1	-0.004	0.046	-9999	-0.55	3	3
ATM	0.012	0.029	-9999	-0.59	1	1
MAP2K3	0.018	0.047	-9999	-0.35	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.02	0.064	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.002	0.091	-9999	-0.69	7	7
TXN	0.009	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
GADD45A	0.012	0.04	-9999	-0.82	1	1
GADD45B	0.014	0	-9999	-10000	0	0
MAP3K1	0.014	0	-9999	-10000	0	0
MAP3K6	0.012	0.029	-9999	-0.59	1	1
MAP3K7	0.014	0	-9999	-10000	0	0
MAP3K4	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.021	-9999	-0.43	1	1
TAK1/TAB family	0	0.009	-9999	-0.18	1	1
RAC1/OSM/MEKK3	-0.009	0.068	-9999	-0.5	8	8
TRAF2	0.008	0.07	-9999	-0.82	3	3
RAC1/OSM/MEKK3/MKK3	-0.013	0.051	-9999	-0.42	3	3
TRAF6	0.008	0.018	-9999	-0.37	1	1
RAC1	0.014	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.14	0.27	-9999	-0.6	107	107
CCM2	-0.002	0.11	-9999	-0.82	8	8
CaM/Ca2+/CAMKIIB	-0.095	0.16	-9999	-0.38	107	107
MAPK11	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.084	0.15	-9999	-0.5	6	6
OSM/MEKK3	-0.012	0.085	-9999	-0.63	8	8
TAOK1	0.011	0.054	-9999	-0.35	9	9
TAOK2	0.018	0.018	-9999	-0.35	1	1
TAOK3	0.018	0.018	-9999	-0.35	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.014	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAP3K10	0.012	0.04	-9999	-0.82	1	1
MAP3K3	0.014	0	-9999	-10000	0	0
TRX/ASK1	0.017	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.007	0.053	-9999	-0.47	4	4

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.023	0.097	-10000	0	-0.43	23	23
ATM	0.012	0.029	-10000	0	-0.59	1	1
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.027	0.018	-10000	0	-0.34	1	1
protein ubiquitination	-0.02	0.078	-10000	0	-0.45	4	4
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.004	0.037	-10000	0	-0.57	1	1
FANCF	0.009	0.051	-10000	0	-0.59	3	3
BRCA1	0.014	0	-10000	0	-10000	0	0
CCNE1	0.006	0.08	-10000	0	-0.82	4	4
CDK2/Cyclin E1	-0.006	0.061	-10000	0	-0.63	4	4
FANCG	0.01	0.057	-10000	0	-0.82	2	2
BRCA1/BACH1/BARD1	-0.023	0.097	-10000	0	-0.43	23	23
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.014	0	-10000	0	-10000	0	0
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	0.01	0.057	-10000	0	-0.82	2	2
DNA repair	0.058	0.079	-10000	0	-0.5	1	1
BRCA1/BARD1/ubiquitin	-0.023	0.097	-10000	0	-0.43	23	23
BARD1/DNA-PK	-0.017	0.071	-10000	0	-10000	0	0
FANCL	0.01	0.057	-10000	0	-0.82	2	2
mRNA polyadenylation	0.023	0.096	0.42	23	-10000	0	23
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.068	-10000	0	-0.41	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.019	0.081	-10000	0	-0.36	23	23
BRCA1/BARD1/P53	-0.02	0.077	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.019	0.081	-10000	0	-0.36	23	23
BRCA1/BACH1	0.014	0	-10000	0	-10000	0	0
BARD1	-0.019	0.14	-10000	0	-0.59	23	23
PCNA	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.019	0.081	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	-0.019	0.081	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.018	0.075	-10000	0	-0.49	1	1
BARD1/DNA-PK/P53	-0.018	0.071	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.023	0.097	-10000	0	-0.43	23	23
BRCA1/BARD1/CTIP	-0.018	0.073	-10000	0	-10000	0	0
FA complex	0.038	0.042	-10000	0	-0.51	1	1
BARD1/EWS	-0.023	0.097	-10000	0	-0.43	23	23
RBBP8	0.024	0.022	-10000	0	-0.43	1	1
TP53	0.008	0.058	-10000	0	-0.59	4	4
TOPBP1	0.014	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.02	0.077	-10000	0	-10000	0	0
BRCA1/BARD1	-0.021	0.079	-10000	0	-0.46	4	4
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.024	0.099	-10000	0	-0.44	23	23
CDK2	0.014	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.012	0.04	-10000	0	-0.82	1	1
RAD50	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.023	0.097	-10000	0	-0.43	23	23
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.022	0.048	-9999	-0.54	1	1
BIRC5	-0.024	0.17	-9999	-0.82	19	19
NFKBIA	0.027	0.04	-9999	-10000	0	0
CPEB1	-0.077	0.23	-9999	-0.64	58	58
AKT1	0.027	0.04	-9999	-10000	0	0
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.003	0.033	-9999	-10000	0	0
NDEL1/TACC3	-0.005	0.044	-9999	-0.47	2	2
GADD45A	0.012	0.04	-9999	-0.82	1	1
GSK3B	0.013	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.022	0.048	-9999	-0.54	1	1
MDM2	0.014	0	-9999	-10000	0	0
JUB	0.012	0.029	-9999	-0.59	1	1
TPX2	0.015	0.077	-9999	-0.63	6	6
TP53	0.025	0.042	-9999	-0.31	4	4
DLG7	0.016	0.04	-9999	-0.29	7	7
AURKAIP1	0.012	0.04	-9999	-0.82	1	1
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.005	0.046	-9999	-0.49	2	2
G2/M transition of mitotic cell cycle	-0.003	0.033	-9999	-10000	0	0
AURKA	0.02	0.047	-9999	-0.34	7	7
AURKB	-0.005	0.034	-9999	-0.26	6	6
CDC25B	-0.017	0.074	-9999	-0.32	20	20
G2/M transition checkpoint	-0.004	0.041	-9999	-0.56	1	1
mRNA polyadenylation	-0.053	0.13	-9999	-0.37	57	57
Aurora A/CPEB	-0.054	0.14	-9999	-0.38	57	57
Aurora A/TACC1/TRAP/chTOG	-0.003	0.032	-9999	-10000	0	0
BRCA1	0.014	0	-9999	-10000	0	0
centrosome duplication	0.022	0.048	-9999	-0.54	1	1
regulation of centrosome cycle	-0.005	0.043	-9999	-0.46	2	2
spindle assembly	-0.004	0.032	-9999	-10000	0	0
TDRD7	0.014	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.023	0.1	-9999	-0.48	19	19
CENPA	-0.006	0.037	-9999	-0.38	3	3
Aurora A/PP2A	0.023	0.039	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.032	0.038	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.042	-9999	-0.31	4	4
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.012	0.029	-9999	-0.59	1	1
Ajuba/Aurora A	-0.004	0.041	-9999	-0.56	1	1
mitotic prometaphase	0.001	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.047	-9999	-0.34	7	7
TACC1	0.012	0.029	-9999	-0.59	1	1
TACC3	0.01	0.057	-9999	-0.82	2	2
Aurora A/Antizyme1	-0.004	0.04	-9999	-0.49	1	1
Aurora A/RasGAP	0.022	0.043	-9999	-0.36	1	1
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.026	-9999	-0.54	1	1
Importin alpha/Importin beta/TPX2	0.015	0.077	-9999	-0.63	6	6
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	0.024	0.071	-9999	-0.49	6	6
PAK1	0.012	0.04	-9999	-0.82	1	1
CKAP5	0.014	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.006	0.095	-10000	0	-0.68	8	8
oxygen homeostasis	-0.001	0.017	-10000	0	-10000	0	0
TCEB2	0.012	0.04	-10000	0	-0.82	1	1
TCEB1	0.012	0.04	-10000	0	-0.82	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.021	0.077	-10000	0	-0.53	2	2
EPO	-0.037	0.27	-10000	0	-0.71	28	28
FIH (dimer)	0.012	0.017	-10000	0	-10000	0	0
APEX1	0.014	0.015	-10000	0	-10000	0	0
SERPINE1	-0.25	0.39	-10000	0	-0.81	45	45
FLT1	0.006	0.049	-10000	0	-0.66	1	1
ADORA2A	-0.014	0.23	-10000	0	-0.79	5	5
germ cell development	-0.026	0.25	-10000	0	-0.82	12	12
SLC11A2	-0.011	0.23	-10000	0	-0.87	3	3
BHLHE40	-0.013	0.23	-10000	0	-0.89	4	4
HIF1AN	0.012	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.059	0.1	-10000	0	-0.5	7	7
ETS1	0.025	0.07	-10000	0	-0.8	3	3
CITED2	-0.003	0.092	-10000	0	-1	3	3
KDR	0.003	0.081	-10000	0	-1	2	2
PGK1	-0.011	0.23	-10000	0	-0.82	4	4
SIRT1	0.012	0.029	-10000	0	-0.59	1	1
response to hypoxia	-0.001	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.021	0.26	-10000	0	-0.88	8	8
EPAS1	0.01	0.13	-10000	0	-0.43	8	8
SP1	0.022	0.003	-10000	0	-10000	0	0
ABCG2	-0.017	0.24	-10000	0	-0.86	6	6
EFNA1	-0.011	0.23	-10000	0	-0.88	4	4
FXN	-0.012	0.23	-10000	0	-0.8	4	4
POU5F1	-0.028	0.26	-10000	0	-0.86	12	12
neuron apoptosis	0.021	0.25	0.84	8	-10000	0	8
EP300	0.011	0.041	-10000	0	-0.59	2	2
EGLN3	-0.035	0.19	-10000	0	-0.79	25	25
EGLN2	0.012	0.016	-10000	0	-10000	0	0
EGLN1	0.012	0.017	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.003	0.037	-10000	0	-0.54	2	2
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.014	0.015	-10000	0	-10000	0	0
SLC2A1	-0.019	0.25	-10000	0	-0.85	11	11
TWIST1	-0.023	0.25	-10000	0	-0.83	13	13
ELK1	0.02	0.04	-10000	0	-0.81	1	1
HIF2A/ARNT/Cbp/p300	-0.049	0.093	-10000	0	-0.49	7	7
VEGFA	-0.015	0.24	-10000	0	-0.9	6	6
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.032	0.13	-9999	-0.58	23	23
AKT1	0.085	0.064	-9999	-0.51	1	1
PTK2B	0.029	0.13	-9999	-0.75	3	3
VEGFR2 homodimer/Frs2	0.03	0.073	-9999	-0.57	6	6
CAV1	-0.065	0.24	-9999	-0.82	40	40
CALM1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.014	0.08	-9999	-0.52	6	6
endothelial cell proliferation	0.094	0.068	-9999	-0.47	1	1
mol:Ca2+	0.052	0.071	-9999	-0.55	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.008	0.062	-9999	-0.57	2	2
RP11-342D11.1	0.042	0.07	-9999	-0.55	2	2
CDH5	0.01	0.05	-9999	-0.7	2	2
VEGFA homodimer	-0.006	0.053	-9999	-0.49	5	5
SHC1	0.014	0	-9999	-10000	0	0
SHC2	0.003	0.09	-9999	-0.74	6	6
HRAS/GDP	-0.008	0.06	-9999	-0.66	1	1
SH2D2A	-0.088	0.27	-9999	-0.82	52	52
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.009	0.05	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.068	0.17	-9999	-0.5	58	58
VEGFR1 homodimer	0.012	0.04	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.008	0.057	-9999	-0.55	1	1
GRB10	0.05	0.085	-9999	-0.68	3	3
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PAK1	0.012	0.04	-9999	-0.82	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.01	0.064	-9999	-0.59	1	1
HRAS	0.012	0.04	-9999	-0.82	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.038	0.072	-9999	-0.48	3	3
HIF1A	0.014	0	-9999	-10000	0	0
FRS2	0.006	0.08	-9999	-0.82	4	4
oxygen and reactive oxygen species metabolic process	-0.008	0.061	-9999	-0.56	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.002	0.098	-9999	-0.82	6	6
Nck/Pak	-0.001	0.03	-9999	-0.63	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.01	0.07	-9999	-0.61	2	2
mol:GDP	-0.008	0.056	-9999	-0.54	1	1
mol:NADP	0.073	0.061	-9999	-0.41	1	1
eNOS/Hsp90	0.076	0.058	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
mol:IP3	0.052	0.071	-9999	-0.55	2	2
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.051	-9999	-0.59	3	3
VEGFA	0.006	0.089	-9999	-0.81	5	5
VEGFC	-0.098	0.28	-9999	-0.81	57	57
FAK1/Vinculin	0.056	0.097	-9999	-0.7	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.031	0.12	-9999	-0.73	4	4
PTPN6	0.014	0	-9999	-10000	0	0
EPAS1	0.023	0.025	-9999	-10000	0	0
mol:L-citrulline	0.073	0.061	-9999	-0.41	1	1
ITGAV	0.006	0.075	-9999	-0.76	4	4
PIK3CA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.013	0.075	-9999	-0.57	2	2
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.068	-9999	-0.6	2	2
VEGFR2/3 heterodimer	0.028	0.09	-9999	-0.64	7	7
VEGFB	0.012	0.04	-9999	-0.82	1	1
MAPK11	0.054	0.072	-9999	-0.55	2	2
VEGFR2 homodimer	0.035	0.055	-9999	-0.76	2	2
FLT1	0.012	0.04	-9999	-0.82	1	1
NEDD4	0.016	0.005	-9999	-10000	0	0
MAPK3	0.056	0.069	-9999	-0.54	1	1
MAPK1	0.056	0.069	-9999	-0.54	1	1
VEGFA145/NRP2	-0.01	0.079	-9999	-0.62	7	7
VEGFR1/2 heterodimer	0.034	0.056	-9999	-0.62	3	3
KDR	0.035	0.056	-9999	-0.76	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.011	0.068	-9999	-0.55	2	2
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.058	0.069	-9999	-0.55	1	1
PI3K	-0.01	0.061	-9999	-0.61	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.009	0.066	-9999	-0.61	2	2
FES	0.052	0.072	-9999	-0.56	2	2
GAB1	-0.008	0.059	-9999	-0.65	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.066	-9999	-0.51	7	7
CTNNB1	0.012	0.029	-9999	-0.59	1	1
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.038	0.13	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.009	0.066	-9999	-0.61	2	2
PI3K/GAB1	0.086	0.068	-9999	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.013	0.074	-9999	-0.59	1	1
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.074	0.18	-9999	-0.5	62	62
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.052	0.072	-9999	-0.56	2	2
actin cytoskeleton reorganization	-0.067	0.17	-9999	-0.49	58	58
PTK2	0.051	0.1	-9999	-0.76	2	2
EDG1	0.042	0.07	-9999	-0.55	2	2
mol:DAG	0.052	0.071	-9999	-0.55	2	2
CaM/Ca2+	-0.008	0.057	-9999	-0.54	1	1
MAP2K3	0.052	0.086	-9999	-0.56	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.011	0.078	-9999	-0.69	3	3
PLCG1	0.052	0.072	-9999	-0.56	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.011	0.068	-9999	-0.57	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.009	0.066	-9999	-0.61	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.009	0.066	-9999	-0.51	7	7
cell migration	0.079	0.086	-9999	-0.67	1	1
mol:PI-3-4-5-P3	0.071	0.07	-9999	-0.56	2	2
FYN	0.012	0.04	-9999	-0.82	1	1
VEGFB/NRP1	0.047	0.071	-9999	-0.52	2	2
mol:NO	0.073	0.061	-9999	-0.41	1	1
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.059	-9999	-0.64	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.049	0.087	-9999	-0.69	3	3
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.022	0.16	-9999	-0.74	20	20
NOS3	0.075	0.066	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.015	0.087	-9999	-0.58	6	6
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.058	0.071	-9999	-0.55	1	1
PRKCB	0.05	0.09	-9999	-0.55	1	1
VCL	0.012	0.029	-9999	-0.59	1	1
VEGFA165/NRP1	0.042	0.072	-9999	-0.55	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	-0.01	0.077	-9999	-0.72	3	3
VEGFA165/NRP2	-0.01	0.079	-9999	-0.62	7	7
MAPKKK cascade	-0.01	0.071	-9999	-0.75	2	2
NRP2	0.01	0.057	-9999	-0.82	2	2
VEGFC homodimer	-0.097	0.28	-9999	-0.81	57	57
NCK1	0.014	0	-9999	-10000	0	0
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.056	0.095	-9999	-0.7	2	2
MAP3K13	0.045	0.089	-9999	-0.57	3	3
PDPK1	0.077	0.065	-9999	-0.5	2	2

×

IL2 signaling events mediated by STAT5

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
GAB2	0.012	0.041	-9999	-0.59	2	2
ELF1	-0.014	0.11	-9999	-0.57	3	3
CCNA2	0.012	0.04	-9999	-0.82	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
JAK3	-0.007	0.13	-9999	-0.82	11	11
PIK3R1	0.01	0.051	-9999	-0.59	3	3
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.044	0.12	-9999	-0.6	7	7
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.019	0.034	-9999	-10000	0	0
IL2RA	-0.041	0.22	-9999	-0.7	44	44
IL2RB	-0.001	0.11	-9999	-0.79	8	8
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.012	0.15	-9999	-0.8	14	14
G1/S transition of mitotic cell cycle	0.035	0.081	-9999	-0.68	2	2
PTPN11	0.015	0	-9999	-10000	0	0
CCND2	0.026	0.078	-9999	-0.77	4	4
LCK	-0.005	0.13	-9999	-0.82	10	10
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.004	0.04	-9999	-0.82	1	1
CDK6	0	0.1	-9999	-0.78	7	7
CCND3	0.052	0.1	-9999	-0.61	3	3

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.006	0.075	-9999	-0.76	4	4
CDC42/GTP	-0.02	0.071	-9999	-0.47	4	4
PLCG1	0.019	0.086	-9999	-0.49	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.006	0.061	-9999	-0.63	4	4
cell migration	-0.02	0.07	-9999	-0.46	4	4
S1PR5	0.012	0.029	-9999	-0.59	1	1
S1PR4	-0.025	0.17	-9999	-0.81	20	20
MAPK3	0.019	0.086	-9999	-0.49	4	4
MAPK1	0.019	0.086	-9999	-0.49	4	4
S1P/S1P5/Gi	0.025	0.061	-9999	-0.48	2	2
GNAI1	0.012	0.029	-9999	-0.59	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.006	0.056	-9999	-0.51	5	5
RHOA	0.007	0.11	-9999	-0.46	23	23
S1P/S1P4/Gi	0.011	0.09	-9999	-0.52	4	4
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.015	0.15	-9999	-0.75	16	16
S1P/S1P4/G12/G13	-0.028	0.11	-9999	-0.5	23	23
GNA12	0.006	0.08	-9999	-0.82	4	4
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.015	0.13	-9999	-0.59	20	20
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.018	0.048	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
FYN	0.012	0.04	-9999	-0.82	1	1
MAP3K12	0.01	0.05	-9999	-0.7	2	2
FGR	0.012	0.04	-9999	-0.82	1	1
p38 alpha/TAB1	-0.018	0.041	-9999	-0.3	1	1
PRKG1	-0.022	0.16	-9999	-0.74	20	20
DUSP8	0.014	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.032	0.082	-9999	-0.4	15	15
apoptosis	-0.017	0.04	-9999	-0.29	1	1
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.012	0.029	-9999	-0.59	1	1
DUSP1	-0.022	0.14	-9999	-0.59	25	25
PAK1	0.012	0.04	-9999	-0.82	1	1
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.01	0.068	-9999	-0.49	8	8
TRAF6	0.012	0.04	-9999	-0.82	1	1
RAC1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	-0.002	0.11	-9999	-0.82	8	8
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.022	0.095	-9999	-0.4	5	5
BLK	-0.11	0.28	-9999	-0.78	64	64
HCK	0.007	0.07	-9999	-0.7	4	4
MAP2K3	0.012	0.029	-9999	-0.59	1	1
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	0.01	0.057	-9999	-0.82	2	2
TRAF6/MEKK3	-0.001	0.025	-9999	-0.51	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.031	0.068	-9999	-0.32	1	1
positive regulation of innate immune response	0.03	0.1	-9999	-0.41	5	5
LCK	-0.006	0.13	-9999	-0.82	10	10
p38alpha-beta/MKP7	0.036	0.098	-9999	-0.48	1	1
p38alpha-beta/MKP5	0.034	0.1	-9999	-0.48	1	1
PGK/cGMP	-0.027	0.12	-9999	-0.57	20	20
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.02	0.12	-9999	-0.5	4	4
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.022	0.16	-9999	-0.8	17	17

×

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

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
MET/RANBP9	-0.005	0.056	-9999	-0.58	4	4
CRKL	0.031	0.057	-9999	-0.43	1	1
mol:PIP3	-0.023	0.004	-9999	-10000	0	0
AKT1	0	0.003	-9999	-10000	0	0
PTK2B	0.012	0.029	-9999	-0.59	1	1
RAPGEF1	0.038	0.055	-9999	-0.41	1	1
RANBP10	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.02	0.093	-9999	-0.54	8	8
MAP3K5	0.042	0.059	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.018	0.084	-9999	-0.49	8	8
AP1	-0.034	0.13	-9999	-0.37	57	57
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.074	0.25	-9999	-0.7	57	57
STAT3 (dimer)	0.032	0.064	-9999	-0.49	1	1
GAB1/CRKL/SHP2/PI3K	-0.01	0.047	-9999	-0.44	1	1
INPP5D	0.011	0.041	-9999	-0.59	2	2
CBL/CRK	0.038	0.05	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0
ELK1	-0.001	0.027	-9999	-0.26	4	4
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.007	0.03	-9999	-10000	0	0
PAK1	0.007	0.024	-9999	-0.48	1	1
HGF/MET/RANBP10	-0.02	0.093	-9999	-0.54	8	8
HRAS	0.025	0.078	-9999	-0.61	1	1
DOCK1	0.036	0.058	-9999	-0.41	1	1
GAB1	0.025	0.055	-9999	-0.28	1	1
CRK	0.032	0.053	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.019	0.089	-9999	-0.48	12	12
JUN	0.014	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.01	0.047	-9999	-0.29	4	4
PIK3R1	0.009	0.051	-9999	-0.59	3	3
cell morphogenesis	0.059	0.072	-9999	-0.46	1	1
GRB2/SHC	0.022	0.045	-9999	-10000	0	0
FOS	-0.068	0.21	-9999	-0.59	57	57
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.001	0.027	-9999	-0.26	4	4
HGF/MET/MUC20	-0.021	0.095	-9999	-0.44	20	20
cell migration	0.021	0.045	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
MET/RANBP10	-0.005	0.056	-9999	-0.58	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.025	0.067	-9999	-0.52	1	1
MET/MUC20	-0.006	0.057	-9999	-0.58	4	4
RAP1B	0.043	0.056	-9999	-0.39	2	2
RAP1A	0.044	0.052	-9999	-0.38	1	1
HGF/MET/RANBP9	-0.02	0.093	-9999	-0.54	8	8
RAF1	0.032	0.074	-9999	-0.57	1	1
STAT3	0.032	0.065	-9999	-0.5	1	1
cell proliferation	0.043	0.08	-9999	-0.44	1	1
RPS6KB1	0.011	0.019	-9999	-10000	0	0
MAPK3	-0.006	0.024	-9999	-0.26	3	3
MAPK1	-0.006	0.024	-9999	-0.26	3	3
RANBP9	0.014	0	-9999	-10000	0	0
MAPK8	0.05	0.086	-9999	-0.48	7	7
SRC	0.033	0.063	-9999	-0.49	1	1
PI3K	0.019	0.055	-9999	-0.47	1	1
MET/Glomulin	0.008	0.053	-9999	-0.52	4	4
SOS1	0.014	0	-9999	-10000	0	0
MAP2K1	0.039	0.07	-9999	-0.52	1	1
MET	0.006	0.075	-9999	-0.76	4	4
MAP4K1	0.035	0.062	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
MAP2K2	0.039	0.07	-9999	-0.52	1	1
BAD	0.008	0.003	-9999	-10000	0	0
MAP2K4	0.048	0.056	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.009	0.045	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
SH3KBP1	0.014	0	-9999	-10000	0	0
HGS	0.014	0.048	-9999	-10000	0	0
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.012	0.13	-9999	-0.66	16	16
RASA1	0.012	0.029	-9999	-0.59	1	1
NCK1	0.014	0	-9999	-10000	0	0
PTPRJ	0.014	0	-9999	-10000	0	0
NCK/PLCgamma1	0.023	0.049	-9999	-10000	0	0
PDPK1	-0.01	0.003	-9999	-10000	0	0
HGF/MET/SHIP	-0.022	0.099	-9999	-0.56	9	9

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.015	0.072	-9999	-0.54	1	1
forebrain development	-0.023	0.16	-9999	-0.52	15	15
GNAO1	0.005	0.075	-9999	-0.76	4	4
SMO/beta Arrestin2	0.002	0.091	-9999	-0.44	17	17
SMO	-0.011	0.12	-9999	-0.6	17	17
ARRB2	0.013	0.005	-9999	-10000	0	0
GLI3/SPOP	0.056	0.036	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0.014	0	-9999	-10000	0	0
GNAI2	0.013	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0.006	0.015	-9999	-10000	0	0
GNAI1	0.011	0.03	-9999	-0.59	1	1
XPO1	0.015	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.063	0.12	-9999	-0.53	6	6
SAP30	0.014	0.001	-9999	-10000	0	0
mol:GDP	-0.011	0.12	-9999	-0.6	17	17
MIM/GLI2A	0.012	0.025	-9999	-10000	0	0
IFT88	0.014	0	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GLI2	0.028	0.063	-9999	-10000	0	0
GLI3	0.051	0.039	-9999	-10000	0	0
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0	-9999	-10000	0	0
GNG2	0.014	0	-9999	-10000	0	0
Gi family/GTP	0.013	0.092	-9999	-0.5	6	6
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.057	0.036	-9999	-10000	0	0
GLI2/Su(fu)	0.033	0.069	-9999	-10000	0	0
FOXA2	-0.094	0.23	-9999	-0.67	58	58
neural tube patterning	-0.023	0.16	-9999	-0.52	15	15
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.022	0.048	-9999	-0.38	1	1
GNB1	0.014	0	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
CSNK1G3	0.014	0	-9999	-10000	0	0
MTSS1	0.012	0.025	-9999	-10000	0	0
embryonic limb morphogenesis	-0.023	0.16	-9999	-0.52	15	15
SUFU	0.018	0.053	-9999	-0.42	1	1
LGALS3	0.011	0.041	-9999	-0.59	2	2
catabolic process	0.066	0.055	-9999	-10000	0	0
GLI3A/CBP	-0.023	0.11	-9999	-10000	0	0
KIF3A	0.014	0	-9999	-10000	0	0
GLI1	-0.024	0.16	-9999	-0.53	15	15
RAB23	0.01	0.057	-9999	-0.82	2	2
CSNK1A1	0.014	0	-9999	-10000	0	0
IFT172	0.014	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.021	0.056	-9999	-0.44	2	2
GNAZ	-0.016	0.15	-9999	-0.75	16	16
RBBP4	0.011	0.041	-9999	-0.59	2	2
CSNK1G1	0.014	0	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.033	0.058	-9999	-10000	0	0
STK36	0.014	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.022	0.081	-9999	-0.43	6	6
PTCH1	-0.022	0.19	-9999	-1.1	7	7
MIM/GLI1	-0.039	0.21	-9999	-0.67	18	18
CREBBP	-0.023	0.11	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.05	0.024	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.038	0.072	-10000	0	-0.4	3	3
BAG4	0.011	0.041	-10000	0	-0.59	2	2
BAD	0.03	0.027	-10000	0	-10000	0	0
NFKBIA	0.014	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.15	-10000	0	-0.82	15	15
BAX	0.03	0.027	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.013	0.02	-10000	0	-0.095	4	4
IKBKB	0.045	0.069	-10000	0	-10000	0	0
MAP2K2	0.042	0.029	-10000	0	-10000	0	0
MAP2K1	0.042	0.029	-10000	0	-10000	0	0
SMPD1	0.019	0.02	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.17	-10000	0	-0.56	8	8
MAP2K4	0.037	0.027	-10000	0	-10000	0	0
protein ubiquitination	0.046	0.07	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.047	0.032	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.037	0.029	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.023	0.028	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.03	0.028	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.045	0.029	-10000	0	-10000	0	0
MAPK1	0.045	0.029	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	-0.02	0.17	-10000	0	-0.44	55	55
KSR1	0.03	0.029	-10000	0	-10000	0	0
MAPK8	0.038	0.046	-10000	0	-0.32	1	1
TRAF2	0.008	0.07	-10000	0	-0.82	3	3
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.045	0.069	-10000	0	-10000	0	0
TNF R/SODD	-0.002	0.029	-10000	0	-0.43	2	2
TNF	-0.025	0.17	-10000	0	-0.77	21	21
CYCS	0.033	0.028	-10000	0	-10000	0	0
IKBKG	0.045	0.069	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.031	0.075	-10000	0	-0.43	4	4
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.033	0.028	0.14	3	-10000	0	3
TNF/TNF R/SODD	-0.027	0.11	-10000	0	-0.54	17	17
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.02	-10000	0	-10000	0	0
NSMAF	0.038	0.071	-10000	0	-0.4	3	3
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0	0.099	-10000	0	-0.7	8	8

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0	-10000	0	-10000	0	0
NFATC1	0.061	0.014	-10000	0	-10000	0	0
NFATC2	0.025	0.063	-10000	0	-0.32	5	5
NFATC3	0.024	0.021	-10000	0	-0.4	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.014	0.076	-10000	0	-0.46	3	3
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	-0.038	0.11	-10000	0	-0.46	21	21
BCL2/BAX	-0.01	0.073	-10000	0	-0.53	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.003	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.002	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.021	0.072	-10000	0	-0.43	3	3
Calcineurin A alpha-beta B1/BCL2	0	0.099	-10000	0	-0.7	8	8
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.02	0.071	0.42	3	-10000	0	3
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	0.007	0.07	-10000	0	-0.7	4	4
MAP3K8	0.011	0.041	-10000	0	-0.59	2	2
NFAT4/CK1 alpha	-0.001	0.011	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.017	0.059	-10000	0	-0.38	5	5
CABIN1	0.014	0.077	-10000	0	-0.46	3	3
CALM1	0.014	0.002	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.014	0	-10000	0	-10000	0	0
CAMK4	-0.031	0.18	-10000	0	-0.78	24	24
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.028	0.13	-10000	0	-0.63	19	19
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.004	0.077	-10000	0	-0.59	7	7
MAPK9	0.014	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
FKBP1A	0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.001	0.019	-10000	0	-10000	0	0
PRKCH	0.014	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.029	-10000	0	-0.42	2	2
CASP3	0.014	0.002	-10000	0	-10000	0	0
PIM1	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.023	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.045	0.02	-10000	0	-10000	0	0
PRKCB	-0.001	0.11	-10000	0	-0.76	8	8
PRKCE	0.014	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.03	0.019	-10000	0	-0.36	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.014	0	-10000	0	-10000	0	0
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.029	-10000	0	-0.59	1	1
PRKCA	0.012	0.04	-10000	0	-0.82	1	1
PRKCG	-0.076	0.25	-10000	0	-0.82	44	44
PRKCQ	0.003	0.086	-10000	0	-0.66	7	7
FKBP38/BCL2	-0.01	0.073	-10000	0	-0.53	8	8
EP300	0.011	0.041	-10000	0	-0.59	2	2
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.061	0.042	-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	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.029	0.12	-10000	0	-0.52	24	24
NFATc/ERK1	0.066	0.014	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.038	0.11	-10000	0	-0.46	21	21
NR4A1	0.044	0.11	-10000	0	-0.56	11	11
GSK3B	0.014	0.002	-10000	0	-10000	0	0
positive T cell selection	0.024	0.021	-10000	0	-0.4	1	1
NFAT1/CK1 alpha	-0.012	0.036	-10000	0	-0.37	1	1
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.002	-10000	0	-10000	0	0
AKAP5	-0.024	0.17	-10000	0	-0.82	19	19
MEF2D	0.014	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.066	0.017	-10000	0	-10000	0	0
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0	0.099	-10000	0	-0.7	8	8

×

TCGA08_rtk_signaling

Figure S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S110. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.001	0.091	-9999	-0.65	8	8
HRAS	0.012	0.04	-9999	-0.82	1	1
EGFR	-0.017	0.15	-9999	-0.79	16	16
AKT	0.037	0.047	-9999	-0.3	7	7
FOXO3	0.014	0	-9999	-10000	0	0
AKT1	0.014	0	-9999	-10000	0	0
FOXO1	0.014	0	-9999	-10000	0	0
AKT3	0	0.11	-9999	-0.82	7	7
FOXO4	0.011	0.041	-9999	-0.59	2	2
MET	0.006	0.075	-9999	-0.76	4	4
PIK3CA	0.014	0	-9999	-10000	0	0
PIK3CB	0.014	0	-9999	-10000	0	0
NRAS	0.014	0	-9999	-10000	0	0
PIK3CG	-0.024	0.17	-9999	-0.75	21	21
PIK3R3	0.012	0.029	-9999	-0.59	1	1
PIK3R2	0.014	0	-9999	-10000	0	0
NF1	0.014	0	-9999	-10000	0	0
RAS	0.017	0.048	-9999	-0.35	1	1
ERBB2	0.008	0.07	-9999	-0.82	3	3
proliferation/survival/translation	-0.031	0.028	-9999	-10000	0	0
PI3K	0.023	0.053	-9999	-0.26	3	3
PIK3R1	0.009	0.051	-9999	-0.59	3	3
KRAS	0.01	0.057	-9999	-0.82	2	2
FOXO	0.048	0.029	-9999	-0.17	1	1
AKT2	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.003	0.031	-9999	-10000	0	0
DAPP1	0.013	0.092	-9999	-0.34	10	10
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.001	0.16	-9999	-0.67	12	12
mol:DAG	0.028	0.086	-9999	-0.3	8	8
HRAS	0.013	0.04	-9999	-0.81	1	1
RAP1A	0.014	0.002	-9999	-10000	0	0
ARF5/GDP	0.04	0.041	-9999	-10000	0	0
PLCG2	0.012	0.029	-9999	-0.59	1	1
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.003	0.034	-9999	-0.4	3	3
ARF1/GTP	-0.003	0.03	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.003	0.033	-9999	-0.4	3	3
ADAP1	-0.003	0.034	-9999	-10000	0	0
ARAP3	-0.003	0.033	-9999	-0.4	3	3
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.014	0	-9999	-10000	0	0
ARHGEF6	0.006	0.065	-9999	-0.59	5	5
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.014	0.002	-9999	-10000	0	0
FYN	0.012	0.04	-9999	-0.82	1	1
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.012	0.04	-9999	-0.82	1	1
mol:Ca2+	0.027	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.006	0.065	-9999	-0.59	5	5
ZAP70	-0.021	0.16	-9999	-0.76	19	19
mol:IP3	0.031	0.063	-9999	-10000	0	0
LYN	0.012	0.029	-9999	-0.59	1	1
ARF1/GDP	0.04	0.041	-9999	-10000	0	0
RhoA/GDP	-0.004	0.032	-9999	-0.42	1	1
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.048	0.18	-9999	-0.59	43	43
actin cytoskeleton reorganization	0.063	0.045	-9999	-0.41	1	1
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.03	0.027	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0	0.004	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.003	0.031	-9999	-10000	0	0
RhoA/GTP	-0.003	0.032	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.018	0.17	-9999	-0.68	14	14
BLK	-0.11	0.28	-9999	-0.78	64	64
PDPK1	0.014	0	-9999	-10000	0	0
CYTH1	-0.003	0.032	-9999	-10000	0	0
HCK	0.007	0.07	-9999	-0.7	4	4
CYTH3	-0.003	0.032	-9999	-10000	0	0
CYTH2	-0.003	0.032	-9999	-10000	0	0
KRAS	0.011	0.057	-9999	-0.81	2	2
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.003	0.034	-9999	-0.45	2	2
SGK1	-0.004	0.037	-9999	-0.49	2	2
INPP5D	0.011	0.041	-9999	-0.59	2	2
mol:GDP	0.034	0.043	-9999	-0.32	1	1
SOS1	0.014	0	-9999	-10000	0	0
SYK	0.011	0.041	-9999	-0.59	2	2
ARF6/GDP	-0.004	0.031	-9999	-0.42	1	1
mol:PI-3-4-5-P3	-0.003	0.034	-9999	-0.4	3	3
ARAP3/RAP1A/GTP	-0.003	0.034	-9999	-0.4	3	3
VAV1	0.005	0.071	-9999	-0.59	6	6
mol:PI-3-4-P2	0.022	0.031	-9999	-0.43	2	2
RAS family/GTP/PI3K Class I	0.03	0.037	-9999	-0.41	3	3
PLEKHA1	0.03	0.027	-9999	-10000	0	0
Rac1/GDP	0.04	0.041	-9999	-10000	0	0
LAT	-0.006	0.13	-9999	-0.82	10	10
Rac1/GTP	0.035	0.056	-9999	-0.35	1	1
ITK	-0.015	0.072	-9999	-0.43	7	7
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.028	0.11	-9999	-0.44	9	9
LCK	-0.006	0.13	-9999	-0.82	10	10
BTK	-0.004	0.038	-9999	-0.43	1	1

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.25	0.3	-10000	0	-0.59	187	187
CLTC	0.034	0.015	-10000	0	-0.27	1	1
calcium ion-dependent exocytosis	0.029	0.009	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.024	-10000	0	-0.5	1	1
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.03	0.016	-10000	0	-10000	0	0
CPE	0.011	0.07	-10000	0	-0.52	7	7
CTNNB1	0.012	0.029	-10000	0	-0.59	1	1
membrane fusion	0.028	0.009	-10000	0	-10000	0	0
CTNND1	0.033	0.024	-10000	0	-0.46	1	1
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0.008	-10000	0	-10000	0	0
TSHR	-0.01	0.12	-10000	0	-0.55	21	21
INS	0.012	0.019	-10000	0	-0.26	2	2
BIN1	-0.002	0.11	-10000	0	-0.79	8	8
mol:Choline	0.028	0.009	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.028	-10000	0	-0.55	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.024	-10000	0	-0.5	1	1
JUP	0.03	0.021	-10000	0	-0.29	1	1
ASAP2/amphiphysin II	-0.009	0.065	-10000	0	-0.5	7	7
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.028	0.025	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.026	0.39	1	-10000	0	1
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	0.026	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.016	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.014	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.014	0	-10000	0	-10000	0	0
exocyst	0.047	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	0.024	-10000	0	-0.46	1	1
NME1	0.019	0.028	-10000	0	-0.55	1	1
clathrin coat assembly	0.034	0.015	-10000	0	-0.27	1	1
IL2RA	0.006	0.075	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.11	0.12	-10000	0	-0.49	1	1
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.001	0.014	-10000	0	-0.28	1	1
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0.008	-10000	0	-10000	0	0
SDC1	0.031	0.01	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.027	-10000	0	-0.55	1	1
EXOC7	0.014	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.003	0.026	-10000	0	-0.4	1	1
mol:Phosphatidic acid	0.028	0.009	-10000	0	-10000	0	0
endocytosis	0.009	0.065	0.5	7	-10000	0	7
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.02	0.081	-10000	0	-0.55	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.026	0.025	-10000	0	-0.5	1	1
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.025	0.069	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.023	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0	0	-9999	-10000	0	0
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.001	0.03	-9999	-0.63	1	1
GATA1/HDAC5	-0.001	0.03	-9999	-0.63	1	1
GATA2/HDAC5	-0.007	0.064	-9999	-0.59	5	5
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.049	0.22	-9999	-0.82	32	32
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
GATA2	0.004	0.085	-9999	-0.77	5	5
HDAC4/RFXANK	-0.001	0.03	-9999	-0.63	1	1
BCOR	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	0.025	0.064	-9999	-10000	0	0
ADRBK1	0.014	0	-9999	-10000	0	0
HDAC4	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.014	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.014	0	-9999	-10000	0	0
HDAC6	0.014	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.03	-9999	-0.63	1	1
CAMK4	-0.031	0.18	-9999	-0.78	24	24
Tubulin/HDAC6	0	0	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
GATA1	0.009	0.041	-9999	-0.82	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
NR3C1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC4	0.032	0	-9999	-10000	0	0
SRF	0.014	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	0	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.029	0.12	-9999	-0.54	20	20
HDAC4/ER alpha	-0.033	0.13	-9999	-0.56	25	25
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.025	0.064	-9999	-10000	0	0
cell motility	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.014	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.014	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.031	0.18	-9999	-0.74	25	25
HDAC6/HDAC11	-0.001	0.021	-9999	-0.43	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.001	0.098	-9999	-0.75	7	7
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.007	0.053	-9999	-0.46	5	5
GNG2	0.014	0	-9999	-10000	0	0
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.014	0	-9999	-10000	0	0
HDAC11	0.012	0.029	-9999	-0.59	1	1
HSP90AA1	0.014	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
ANKRA2	0.014	0	-9999	-10000	0	0
RFXANK	0.012	0.04	-9999	-0.82	1	1
nuclear import	-0.031	0	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.011	0.076	-9999	-0.54	8	8
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.003	0.019	-9999	-10000	0	0
AURKB	0.004	0.09	-9999	-0.82	5	5
AURKC	0.005	0.081	-9999	-0.73	5	5

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.012	0.007	-10000	0	-10000	0	0
BUB1B	0.022	0.024	-10000	0	-10000	0	0
PLK1	0.017	0.02	-10000	0	-0.17	1	1
PLK1S1	0.015	0.016	-10000	0	-0.17	2	2
KIF2A	0.025	0.018	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.017	0.02	-10000	0	-0.17	1	1
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.011	0.1	-10000	0	-0.47	17	17
WEE1	0.022	0.027	-10000	0	-10000	0	0
cytokinesis	0.031	0.031	-10000	0	-10000	0	0
PP2A-alpha B56	0.035	0.013	-10000	0	-10000	0	0
AURKA	0.014	0.028	-10000	0	-0.19	7	7
PICH/PLK1	0.022	0.089	-10000	0	-0.38	19	19
CENPE	0.025	0.018	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.025	0.018	-10000	0	-10000	0	0
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	0.013	0.025	-10000	0	-0.18	6	6
PAK1	0.011	0.04	-10000	0	-0.81	1	1
SPC24	-0.004	0.12	-10000	0	-0.82	9	9
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	0.011	0.035	-10000	0	-0.21	9	9
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.015	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.01	0.01	-10000	0	-0.067	3	3
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.013	7	7
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.009	-10000	0	-10000	0	0
spindle elongation	0.017	0.02	-10000	0	-0.17	1	1
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	-0.002	0.01	-10000	0	-10000	0	0
TPT1	0.016	0.01	-10000	0	-10000	0	0
CDC25C	0.013	0.035	-10000	0	-0.25	7	7
CDC25B	-0.023	0.17	-10000	0	-0.81	19	19
SGOL1	0.012	0.007	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.018	0.082	-10000	0	-0.4	19	19
CDC14B	0.009	0.038	-10000	0	-0.44	3	3
CDC20	0.002	0.098	-10000	0	-0.82	6	6
PLK1/PBIP1	-0.004	0.035	-10000	0	-0.49	2	2
mitosis	0	0.006	0.041	7	-0.022	2	9
FBXO5	0.021	0.02	-10000	0	-10000	0	0
CDC2	0.001	0.004	-10000	0	-0.017	19	19
NDC80	-0.002	0.11	-10000	0	-0.82	8	8
metaphase plate congression	0.016	0.012	-10000	0	-10000	0	0
ERCC6L	-0.017	0.076	-10000	0	-0.37	19	19
NLP/gamma Tubulin	0.014	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	-0.011	2	2
PPP1R12A	0.014	0.001	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-0.011	2	2
PLK1/PRC1-2	0.031	0.016	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.009	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.018	0.039	-10000	0	-0.47	2	2
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.031	-10000	0	-0.38	1	1
microtubule-based process	0.023	0.017	-10000	0	-10000	0	0
Golgi organization	0.017	0.02	-10000	0	-0.17	1	1
Cohesin/SA2	-0.002	0.011	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0.001	-10000	0	-10000	0	0
KIF20A	0.014	0	-10000	0	-10000	0	0
APC/C/CDC20	0.016	0.067	-10000	0	-0.53	6	6
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.004	0.035	-10000	0	-0.48	2	2
PRC1	0.014	0	-10000	0	-10000	0	0
ECT2	0.019	0.058	-10000	0	-0.49	5	5
C13orf34	0.019	0.038	-10000	0	-0.48	2	2
NUDC	0.016	0.012	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.022	0.024	-10000	0	-10000	0	0
spindle assembly	0.018	0.015	-10000	0	-0.11	1	1
spindle stabilization	0.015	0.016	-10000	0	-0.17	2	2
APC/C/HCDH1	0.016	0.032	-10000	0	-0.37	3	3
MKLP2/PLK1	0.024	0.017	-10000	0	-10000	0	0
CCNB1	0.014	0.003	-10000	0	-10000	0	0
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	0.017	0.059	-10000	0	-0.43	7	7
TUBG1	0.016	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.018	0.08	-10000	0	-0.39	19	19
MLF1IP	0.009	0.045	-10000	0	-0.65	2	2
INCENP	0.013	0.001	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.01	0.047	0.42	2	-10000	0	2
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.006	0.056	-10000	0	-0.51	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.006	0.075	-10000	0	-0.76	4	4
RhoA/GTP	-0.01	0.047	-10000	0	-0.43	2	2
negative regulation of cAMP metabolic process	0.025	0.061	-10000	0	-0.48	2	2
GNAZ	-0.015	0.15	-10000	0	-0.75	16	16
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.006	0.08	-10000	0	-0.82	4	4
S1PR5	0.012	0.029	-10000	0	-0.59	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.025	0.061	-10000	0	-0.48	2	2
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
GNAI1	0.012	0.029	-10000	0	-0.59	1	1

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.049	0.04	-10000	0	-0.38	1	1
adherens junction organization	0.039	0.053	-10000	0	-0.43	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.039	0.088	-10000	0	-10000	0	0
FMN1	0.026	0.084	-10000	0	-0.56	2	2
mol:IP3	-0.004	0.032	-10000	0	-0.4	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.035	0.046	-10000	0	-0.62	1	1
CTNNB1	0.012	0.029	-10000	0	-0.59	1	1
AKT1	0.047	0.04	-10000	0	-0.43	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.057	-10000	0	-0.46	5	5
CTNND1	0.015	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.042	0.043	-10000	0	-0.57	1	1
VASP	0.042	0.044	-10000	0	-0.58	1	1
ZYX	0.042	0.044	-10000	0	-0.58	1	1
JUB	0.042	0.05	-10000	0	-0.56	2	2
EGFR(dimer)	0.024	0.099	-10000	0	-0.44	16	16
E-cadherin/beta catenin-gamma catenin	-0.005	0.048	-10000	0	-0.66	1	1
mol:PI-3-4-5-P3	-0.005	0.036	-10000	0	-0.46	1	1
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
PI3K	-0.005	0.036	-10000	0	-0.47	1	1
FYN	0.047	0.06	-10000	0	-0.58	1	1
mol:Ca2+	0.04	0.037	-10000	0	-0.39	1	1
JUP	0.01	0.041	-10000	0	-0.59	2	2
PIK3R1	0.01	0.051	-10000	0	-0.59	3	3
mol:DAG	-0.004	0.032	-10000	0	-0.4	1	1
CDH1	0.008	0.058	-10000	0	-0.59	4	4
RhoA/GDP	0.039	0.088	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.042	0.043	-10000	0	-0.57	1	1
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.017	0.15	-10000	0	-0.79	16	16
CASR	0.038	0.065	-10000	0	-0.41	6	6
RhoA/GTP	-0.004	0.028	-10000	0	-10000	0	0
AKT2	0.047	0.04	-10000	0	-0.43	1	1
actin cable formation	0.033	0.081	-10000	0	-0.54	2	2
apoptosis	0.005	0.034	0.41	1	-10000	0	1
CTNNA1	0.015	0.001	-10000	0	-10000	0	0
mol:GDP	0.033	0.093	-10000	0	-10000	0	0
PIP5K1A	0.042	0.044	-10000	0	-0.58	1	1
PLCG1	-0.004	0.032	-10000	0	-0.4	1	1
Rac1/GTP	-0.018	0.08	-10000	0	-0.4	16	16
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.006	0.051	-9999	-0.69	1	1
E-cadherin/beta catenin	-0.005	0.046	-9999	-0.43	5	5
CTNNB1	0.012	0.029	-9999	-0.59	1	1
JUP	0.011	0.041	-9999	-0.59	2	2
CDH1	0.008	0.058	-9999	-0.59	4	4

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.012	0.029	-9999	-0.59	1	1
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	0.012	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0.014	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.017	-9999	-0.36	1	1
SMAD2/SMAD2/SMAD4	-0.001	0.013	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
SMAD2/SMAD4	0.021	0.016	-9999	-10000	0	0
MAP3K1	0.014	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.015	0.079	-9999	-0.43	15	15
MAPK3	0.014	0	-9999	-10000	0	0
MAPK1	0.014	0	-9999	-10000	0	0
NUP214	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
CTDSP2	0.014	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
KPNB1	0.014	0	-9999	-10000	0	0
TGFBRAP1	-0.006	0.11	-9999	-0.59	14	14
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.014	0	-9999	-10000	0	0
PIAS4	0.014	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.088	0.027	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
RIP2/NOD2	-0.004	0.048	-9999	-0.56	3	3
NFKBIA	0.05	0	-9999	-10000	0	0
BIRC2	-0.002	0.11	-9999	-0.82	8	8
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.005	0.03	-9999	-10000	0	0
IKK complex/A20	-0.022	0.08	-9999	-10000	0	0
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.048	0.04	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.004	0.023	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.001	0.026	-9999	-0.54	1	1
NOD2	0.008	0.064	-9999	-0.74	3	3
NFKB1	0.017	0	-9999	-10000	0	0
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	-0.012	0.085	-9999	-0.63	8	8
ATM	0.012	0.029	-9999	-0.59	1	1
TNF/TNFR1A	-0.029	0.13	-9999	-0.59	21	21
TRAF6	0.012	0.04	-9999	-0.82	1	1
PRKCA	0.012	0.04	-9999	-0.82	1	1
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.77	21	21
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.05	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
IKK complex	-0.004	0.026	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.005	0.03	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.077	0.088	-10000	0	-0.39	1	1
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.014	0	-10000	0	-10000	0	0
AKT2	0.014	0	-10000	0	-10000	0	0
STXBP4	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.054	0.13	0.29	7	-0.44	1	8
YWHAZ	0.014	0	-10000	0	-10000	0	0
CALM1	0.014	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
YWHAB	0.014	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.014	0	-10000	0	-10000	0	0
ASIP	-0.014	0.14	-10000	0	-0.82	12	12
PRKCI	0.014	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.014	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.029	-10000	0	-0.59	1	1
TRIP10	0.014	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.048	0.023	-10000	0	-10000	0	0
VAMP2	0.014	0	-10000	0	-10000	0	0
SLC2A4	-0.06	0.14	0.31	6	-0.49	1	7
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.028	0	-10000	0	-10000	0	0
SFN	0.007	0.07	-10000	0	-0.7	4	4
LNPEP	0.012	0.029	-10000	0	-0.59	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.02	0.086	-9999	-0.41	17	17
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.076	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
ZFPM1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
FKBP3	0.014	0	-9999	-10000	0	0
Histones	-0.008	0.037	-9999	-10000	0	0
YY1/LSF	0.019	0.065	-9999	-0.62	1	1
SMG5	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.02	0.073	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.023	0.053	-9999	-10000	0	0
SAP18	0.014	0	-9999	-10000	0	0
RELA	0.026	0.065	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
HDAC3/TR2	0.023	0.053	-9999	-10000	0	0
NuRD/MBD3 Complex	0.05	0.014	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.059	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.004	0.085	-9999	-0.77	5	5
GATA1	0.009	0.041	-9999	-0.82	1	1
Mad/Max	-0.004	0.041	-9999	-0.43	4	4
NuRD/MBD3 Complex/GATA1/Fog1	0.061	0.019	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.011	0.041	-9999	-0.59	2	2
MAX	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
NFKBIA	0.018	0.059	-9999	-10000	0	0
KAT2B	-0.015	0.13	-9999	-0.59	20	20
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.046	0.017	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.014	0	-9999	-10000	0	0
CHD3	0.014	0	-9999	-10000	0	0
SAP30	0.014	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.014	0	-9999	-10000	0	0
YY1/HDAC3	0.024	0.073	-9999	-0.54	1	1
YY1/HDAC2	0.019	0.065	-9999	-0.62	1	1
YY1/HDAC1	0.019	0.065	-9999	-0.62	1	1
NuRD/MBD2 Complex (MeCP1)	0.05	0.014	-9999	-10000	0	0
PPARG	-0.13	0.16	-9999	-0.67	9	9
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.023	0.053	-9999	-10000	0	0
MBD3L2	-0.003	0.056	-9999	-0.82	2	2
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.021	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC3	0.018	0.059	-9999	-10000	0	0
HDAC2	0.014	0	-9999	-10000	0	0
YY1	0.016	0.076	-9999	-0.3	21	21
HDAC8	0.014	0	-9999	-10000	0	0
SMAD7	0.014	0	-9999	-10000	0	0
NCOR2	0.014	0	-9999	-10000	0	0
MXD1	0.008	0.058	-9999	-0.59	4	4
STAT3	0.026	0.025	-9999	-0.34	2	2
NFKB1	0.014	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.014	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.011	0.052	-9999	-0.57	1	1
YY1/SAP30/HDAC1	-0.011	0.052	-9999	-0.57	1	1
EP300	0.011	0.041	-9999	-0.59	2	2
STAT3 (dimer non-phopshorylated)	0.026	0.025	-9999	-0.34	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.059	-9999	-10000	0	0
histone deacetylation	0.05	0.014	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.032	0.052	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GATAD2B	0.014	0	-9999	-10000	0	0
GATAD2A	0.014	0	-9999	-10000	0	0
GATA2/HDAC3	0.017	0.077	-9999	-0.54	4	4
GATA1/HDAC1	-0.001	0.03	-9999	-0.63	1	1
GATA1/HDAC3	0.016	0.059	-9999	-0.49	1	1
CHD4	0.014	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.029	0.13	-9999	-0.59	21	21
SIN3/HDAC complex/Mad/Max	0.049	0.025	-9999	-10000	0	0
NuRD Complex	0.059	0.015	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.008	0.037	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
MTA2	0.014	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
SUMO1/HDAC1	0.032	0	-9999	-10000	0	0
HDAC complex	-0.001	0.022	-9999	-10000	0	0
GATA1/Fog1	-0.001	0.03	-9999	-0.63	1	1
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.77	21	21
negative regulation of cell growth	0.048	0.025	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.05	0.014	-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	0.048	0.017	-9999	-10000	0	0
TFCP2	0.014	0	-9999	-10000	0	0
NR2C1	0.014	0	-9999	-10000	0	0
MBD3	0.014	0	-9999	-10000	0	0
MBD2	0.014	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.039	0.048	-9999	-0.62	2	2
PLK1	0.11	0.12	-9999	-0.92	2	2
CDKN1B	0.15	0.057	-9999	-10000	0	0
FOXO3	0.11	0.11	-9999	-0.89	1	1
KAT2B	-0.002	0.13	-9999	-0.58	20	20
FOXO1/SIRT1	0.007	0.035	-9999	-10000	0	0
CAT	0.11	0.12	-9999	-0.99	2	2
CTNNB1	0.012	0.029	-9999	-0.59	1	1
AKT1	0.029	0.01	-9999	-10000	0	0
FOXO1	0.043	0.027	-9999	-10000	0	0
MAPK10	0.027	0.079	-9999	-0.46	2	2
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.1	0.052	-9999	-10000	0	0
response to oxidative stress	0.017	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	0.002	0.08	-9999	-0.71	2	2
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.013	0.042	-9999	-0.59	2	2
BCL2L11	0.043	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.043	0.035	-9999	-0.47	1	1
mol:GDP	0.017	0.011	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
GADD45A	0.13	0.057	-9999	-0.48	1	1
YWHAQ	0.014	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.08	0.018	-9999	-10000	0	0
MST1	0.018	0.082	-9999	-0.72	5	5
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.062	0.028	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.04	0.043	-9999	-10000	0	0
MAPK9	0.045	0.005	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.005	0.034	-9999	-0.59	1	1
SOD2	0.16	0.063	-9999	-10000	0	0
RBL2	0.12	0.078	-9999	-10000	0	0
RAL/GDP	0.035	0.012	-9999	-10000	0	0
CHUK	0.026	0.009	-9999	-10000	0	0
Ran/GTP	0.015	0.001	-9999	-10000	0	0
CSNK1G2	0.014	0	-9999	-10000	0	0
RAL/GTP	0.044	0.008	-9999	-10000	0	0
CSNK1G1	0.014	0	-9999	-10000	0	0
FASLG	-0.024	0.27	-9999	-0.86	34	34
SKP2	0.012	0.04	-9999	-0.82	1	1
USP7	0.015	0	-9999	-10000	0	0
IKBKB	0.026	0.009	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.8	1	1
FOXO1-3a-4/beta catenin	0.004	0.034	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.043	0.035	-9999	-0.47	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.024	0.042	-9999	-0.58	2	2
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0.001	-9999	-10000	0	0
ZFAND5	0.11	0.047	-9999	-10000	0	0
SFN	0.007	0.07	-9999	-0.7	4	4
CDK2	0.014	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.075	0.038	-9999	-10000	0	0
CREBBP	0.014	0.005	-9999	-10000	0	0
FBXO32	0.1	0.15	-9999	-1.3	3	3
BCL6	0.12	0.078	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

Figure 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
BCL3/RelA	-0.001	0.021	-9999	-0.43	1	1
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.023	0.045	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.045	0.04	-9999	-0.45	1	1
NFKBIA	0.025	0.045	-9999	-0.53	1	1
MAPK14	0.014	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	0.005	0.071	-9999	-0.59	6	6
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.028	0.019	-9999	-0.36	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.032	0.041	-9999	-0.42	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.049	0.039	-9999	-0.44	1	1
SRC	0.014	0	-9999	-10000	0	0
PI3K	-0.003	0.036	-9999	-0.43	3	3
NF kappa B1 p50/RelA	0.032	0.042	-9999	-0.42	1	1
IKBKB	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
SYK	0.011	0.041	-9999	-0.59	2	2
I kappa B alpha/PIK3R1	0.029	0.05	-9999	-0.5	1	1
cell death	0.047	0.038	-9999	-0.42	1	1
NF kappa B1 p105/c-Rel	0.023	0.045	-9999	-10000	0	0
LCK	-0.006	0.13	-9999	-0.82	10	10
BCL3	0.012	0.029	-9999	-0.59	1	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.028	0.089	-9999	-0.43	15	15
KLHL20	-0.01	0.04	-9999	-0.3	2	2
CYFIP2	0.009	0.058	-9999	-0.67	3	3
Rac1/GDP	0.06	0.039	-9999	-10000	0	0
ENAH	0.039	0.055	-9999	-0.46	5	5
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.012	0.04	-9999	-0.82	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.012	0.029	-9999	-0.59	1	1
CDC42/GTP	-0.003	0.025	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.028	-9999	-0.21	3	3
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.04	-9999	-10000	0	0
RAPGEF1	0.053	0.049	-9999	-0.4	1	1
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.006	0.052	-9999	-0.48	5	5
CRK	0.047	0.052	-9999	-0.43	5	5
E-cadherin/gamma catenin/alpha catenin	-0.005	0.048	-9999	-0.69	1	1
alphaE/beta7 Integrin	-0.002	0.029	-9999	-0.43	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
NCKAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.024	-9999	-0.5	1	1
DLG1	0.039	0.055	-9999	-0.46	5	5
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.02	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.005	0.042	-9999	-0.5	1	1
PI3K	-0.004	0.026	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.006	0.056	-9999	-0.5	5	5
TIAM1	0.007	0.065	-9999	-0.59	5	5
E-cadherin(dimer)/Ca2+	-0.004	0.032	-9999	-10000	0	0
AKT1	-0.002	0.015	-9999	-10000	0	0
PIK3R1	0.009	0.051	-9999	-0.59	3	3
CDH1	0.008	0.058	-9999	-0.59	4	4
RhoA/GDP	0.059	0.039	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.029	-9999	-0.22	2	2
CDC42/GDP	0.059	0.039	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.023	0.039	-9999	-0.53	1	1
ITGB7	0.011	0.041	-9999	-0.59	2	2
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.004	0.034	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.004	0.033	-9999	-10000	0	0
mol:GDP	0.057	0.044	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.041	-9999	-0.59	2	2
p120 catenin/RhoA/GDP	-0.004	0.029	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.029	0.05	-9999	-0.25	11	11
NME1	0.012	0.04	-9999	-0.82	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.039	0.055	-9999	-0.46	5	5
regulation of cell-cell adhesion	-0.003	0.022	-9999	-10000	0	0
WASF2	-0.004	0.014	-9999	-10000	0	0
Rap1/GTP	-0.003	0.029	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.006	0.05	-9999	-0.6	2	2
CCND1	0.032	0.062	-9999	-0.32	11	11
VAV2	0.042	0.073	-9999	-0.46	1	1
RAP1/GDP	-0.001	0.031	-9999	-10000	0	0
adherens junction assembly	0.039	0.053	-9999	-0.44	5	5
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.014	0	-9999	-10000	0	0
PIP5K1C	0.014	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.006	0.049	-9999	-0.57	2	2
E-cadherin/beta catenin	-0.004	0.037	-9999	-0.39	4	4
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.039	0.055	-9999	-0.46	5	5
PIK3CA	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.016	0.064	-9999	-0.54	2	2
E-cadherin/beta catenin/alpha catenin	-0.004	0.038	-9999	-10000	0	0
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.053	-9999	-0.49	5	5

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
CHUK	0.014	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.003	0.038	-9999	-0.46	3	3
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.004	0.052	-9999	-0.63	3	3
RELB	0.008	0.07	-9999	-0.82	3	3
NFKB2	0.014	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.004	0.046	-9999	-0.55	3	3
regulation of B cell activation	-0.004	0.046	-9999	-0.55	3	3

×

PLK2 and PLK4 events

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
PLK2	0.012	0.029	-9999	-0.59	1	1
PLK4	0.014	0	-9999	-10000	0	0
regulation of centriole replication	0.024	0.022	-9999	-0.43	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.014	0	-10000	0	-10000	0	0
mol:PIP3	-0.003	0.031	-10000	0	-0.29	5	5
FRAP1	0.015	0.011	-10000	0	-10000	0	0
AKT1	0.028	0.031	-10000	0	-10000	0	0
INSR	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.038	-10000	0	-0.55	2	2
mol:GTP	-0.002	0.022	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.007	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.002	0.019	-10000	0	-10000	0	0
TSC1	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.016	0.025	-10000	0	-0.35	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.029	0.02	-10000	0	-10000	0	0
MAP3K5	0.011	0.001	-10000	0	-10000	0	0
PIK3R1	0.009	0.051	-10000	0	-0.59	3	3
apoptosis	0.011	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	2	2
EIF4B	0.034	0.018	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.013	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.022	0.035	-10000	0	-0.3	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.033	0.015	-10000	0	-10000	0	0
FKBP1A	0.014	0	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.019	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	2	2
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.003	0.028	-10000	0	-10000	0	0
EIF4E	0.014	0	-10000	0	-10000	0	0
ASK1/PP5C	0.023	0.007	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.003	0.023	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	2	-10000	0	2
RPS6	0.014	0	-10000	0	-10000	0	0
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.007	0.027	-10000	0	-0.38	2	2
INS	-0.003	0.056	-10000	0	-0.82	2	2
PTEN	0.013	0	-10000	0	-10000	0	0
PDK2	-0.003	0.028	-10000	0	-10000	0	0
EIF4EBP1	0.007	0.047	-10000	0	-0.38	6	6
PIK3CA	0.014	0	-10000	0	-10000	0	0
PPP2R5D	0.022	0.01	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.035	-10000	0	-0.49	2	2
RHEB	0.014	0	-10000	0	-10000	0	0
EIF4A1	0.014	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.016	0.035	-10000	0	-0.5	2	2
eIF4E/4E-BP1	0.015	0.042	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.04	0	-9999	-10000	0	0
CDKN1A	0.04	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.014	0	-9999	-10000	0	0
FOXO3	0.04	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.014	0	-9999	-10000	0	0
AKT3	0.012	0.049	-9999	-0.36	7	7
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.039	0.022	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.014	0	-9999	-10000	0	0
RAF1	0.014	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.04	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
AKT1/RAF1	0.04	0	-9999	-10000	0	0
EP300	0.011	0.041	-9999	-0.59	2	2
mol:GDP	0.033	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.04	0	-9999	-10000	0	0
YWHAQ	0.014	0	-9999	-10000	0	0
TBC1D4	0.026	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAPKAP1	0.014	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.047	0.015	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0
AKT1S1	0.04	0	-9999	-10000	0	0
CASP9	0.04	0	-9999	-10000	0	0
YWHAB	0.014	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	0.014	0	-9999	-10000	0	0
SRC	0.014	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	0.04	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	0.063	0.018	-9999	-10000	0	0
PDPK1	0.014	0	-9999	-10000	0	0
MDM2	0.04	0	-9999	-10000	0	0
MAPKKK cascade	-0.039	0	-9999	-10000	0	0
MDM2/Cbp/p300	0.051	0.02	-9999	-10000	0	0
TSC1/TSC2	0.047	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.016	-9999	-10000	0	0
glucose import	-0.12	0.17	-9999	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.12	0.17	-9999	-10000	0	0
GSK3A	0.04	0	-9999	-10000	0	0
FOXO1	0.04	0	-9999	-10000	0	0
GSK3B	0.04	0	-9999	-10000	0	0
SFN	0.007	0.07	-9999	-0.7	4	4
G1/S transition of mitotic cell cycle	0.047	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.05	0.021	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
KPNA1	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
RHEB	0.014	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.014	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.032	-9999	-9999
HDAC4	0.014	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.014	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.014	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.014	-9999	-9999
SUMO1/HDAC4	0.032	-9999	-9999
SUMO1/HDAC1	0.032	-9999	-9999
RANGAP1	0.014	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.014	-9999	-9999
UBE2I	0.014	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.014	-9999	-9999
PIAS1	0.014	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-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	-0.003	0.043	-9999	-0.63	2	2
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-10000	0	0
CD4	0.01	0.05	-9999	-0.7	2	2
CLTA	0.014	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	0.01	0.057	-9999	-0.82	2	2
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.018	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.028	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.014	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.014	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	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	-0.49	4	4

pid_entity	TCGA.QK.A6IJ	TCGA.QK.A6II	TCGA.QK.A6IH	TCGA.QK.A652
109_MAP3K5	0.059	-0.16	0.059	0.059
47_PPARGC1A	-0.59	-0.59	-0.59	0.014
105_BMP4	0.014	-0.59	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	-0.82	0.014	0.014
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.019	0.013	0.019	0.013
84_STAT5B	-0.15	-0.33	-0.03	0.048
84_STAT5A	-0.15	-0.33	-0.03	0.048