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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	220
Syndecan-1-mediated signaling events	201
Syndecan-4-mediated signaling events	134
IL4-mediated signaling events	129
Osteopontin-mediated events	103
HIF-1-alpha transcription factor network	102
IL23-mediated signaling events	85
Glypican 2 network	82
amb2 Integrin signaling	72
TCGA08_p53	67

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	0.4427	220	1767	8	-0.35	0.15	1000	-1000	-0.024	-1000
Syndecan-1-mediated signaling events	0.4044	201	6840	34	-0.72	0.014	1000	-1000	-0.074	-1000
Syndecan-4-mediated signaling events	0.2696	134	8995	67	-0.69	0.092	1000	-1000	-0.11	-1000
IL4-mediated signaling events	0.2596	129	11801	91	-1.4	1.2	1000	-1000	-0.2	-1000
Osteopontin-mediated events	0.2072	103	3933	38	-0.44	0.014	1000	-1000	-0.13	-1000
HIF-1-alpha transcription factor network	0.2052	102	7792	76	-1	0.022	1000	-1000	-0.2	-1000
IL23-mediated signaling events	0.1710	85	5155	60	-0.75	0.014	1000	-1000	-0.19	-1000
Glypican 2 network	0.1650	82	328	4	-0.15	-0.14	1000	-1000	-0.044	-1000
amb2 Integrin signaling	0.1449	72	5939	82	-0.6	0.014	1000	-1000	-0.11	-1000
TCGA08_p53	0.1348	67	472	7	-0.27	0.14	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	0.1308	65	4536	69	-0.44	0.024	1000	-1000	-0.068	-1000
Endothelins	0.1187	59	5704	96	-0.56	0.014	1000	-1000	-0.1	-1000
p75(NTR)-mediated signaling	0.0905	45	5635	125	-0.54	0.014	1000	-1000	-0.12	-1000
Ephrin B reverse signaling	0.0905	45	2186	48	-0.16	0.15	1000	-1000	-0.079	-1000
FOXA2 and FOXA3 transcription factor networks	0.0885	44	2056	46	-0.49	0.022	1000	-1000	-0.11	-1000
Visual signal transduction: Rods	0.0865	43	2245	52	-0.43	0.014	1000	-1000	-0.11	-1000
Calcium signaling in the CD4+ TCR pathway	0.0785	39	1227	31	-0.51	0.014	1000	-1000	-0.11	-1000
Effects of Botulinum toxin	0.0744	37	964	26	-0.21	0.014	1000	-1000	-0.079	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0744	37	2895	78	-0.16	0.043	1000	-1000	-0.091	-1000
BMP receptor signaling	0.0704	35	2888	81	-0.36	0.048	1000	-1000	-0.11	-1000
Glypican 1 network	0.0704	35	1690	48	-0.36	0.033	1000	-1000	-0.06	-1000
Signaling events mediated by the Hedgehog family	0.0684	34	1794	52	-0.45	0.067	1000	-1000	-0.1	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0664	33	2271	68	-0.56	0.042	1000	-1000	-0.16	-1000
IL12-mediated signaling events	0.0644	32	2803	87	-0.28	0.089	1000	-1000	-0.16	-1000
Glucocorticoid receptor regulatory network	0.0644	32	3676	114	-0.64	0.26	1000	-1000	-0.088	-1000
Signaling events regulated by Ret tyrosine kinase	0.0644	32	2679	82	-0.18	0.014	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0644	32	3039	93	-0.27	0.15	1000	-1000	-0.1	-1000
Coregulation of Androgen receptor activity	0.0624	31	2394	76	-0.5	0.041	1000	-1000	-0.066	-1000
LPA4-mediated signaling events	0.0584	29	357	12	-0.11	0.021	1000	-1000	-0.036	-1000
Visual signal transduction: Cones	0.0584	29	1125	38	-0.18	0.014	1000	-1000	-0.084	-1000
Canonical Wnt signaling pathway	0.0563	28	1438	51	-0.39	0.11	1000	-1000	-0.083	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0563	28	3478	120	-0.25	0.12	1000	-1000	-0.095	-1000
ErbB4 signaling events	0.0543	27	1868	69	-0.32	0.072	1000	-1000	-0.11	-1000
Caspase cascade in apoptosis	0.0523	26	1971	74	-0.14	0.056	1000	-1000	-0.061	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0523	26	890	34	-0.065	0.014	1000	-1000	-0.075	-1000
Thromboxane A2 receptor signaling	0.0523	26	2782	105	-0.094	0.021	1000	-1000	-0.086	-1000
EPHB forward signaling	0.0523	26	2214	85	-0.26	0.11	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0523	26	2662	99	-0.15	0.034	1000	-1000	-0.11	-1000
PDGFR-beta signaling pathway	0.0523	26	2563	97	-0.13	0.014	1000	-1000	-0.11	-1000
IL1-mediated signaling events	0.0503	25	1554	62	-0.24	0.072	1000	-1000	-0.13	-1000
Nongenotropic Androgen signaling	0.0503	25	1314	52	-0.14	0.041	1000	-1000	-0.086	-1000
IL27-mediated signaling events	0.0483	24	1264	51	-0.18	0.062	1000	-1000	-0.11	-1000
Syndecan-3-mediated signaling events	0.0463	23	835	35	-0.21	0.014	1000	-1000	-0.075	-1000
Regulation of nuclear SMAD2/3 signaling	0.0443	22	3065	136	-0.37	0.36	1000	-1000	-0.092	-1000
Signaling mediated by p38-gamma and p38-delta	0.0443	22	339	15	-0.13	0.024	1000	-1000	-0.049	-1000
Integrins in angiogenesis	0.0443	22	1860	84	-0.44	0.017	1000	-1000	-0.11	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0443	22	754	33	-0.35	0.037	1000	-1000	-0.08	-1000
Presenilin action in Notch and Wnt signaling	0.0423	21	1307	61	-0.39	0.04	1000	-1000	-0.1	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0423	21	1860	88	-0.36	0.067	1000	-1000	-0.14	-1000
Wnt signaling	0.0402	20	142	7	-0.074	0.011	1000	-1000	-0.039	-1000
LPA receptor mediated events	0.0402	20	2118	102	-0.6	0.026	1000	-1000	-0.11	-1000
Signaling events mediated by PTP1B	0.0382	19	1454	76	-0.16	0.03	1000	-1000	-0.11	-1000
IFN-gamma pathway	0.0362	18	1237	68	-0.19	0.036	1000	-1000	-0.12	-1000
Regulation of Telomerase	0.0362	18	1884	102	-0.16	0.044	1000	-1000	-0.12	-1000
Regulation of Androgen receptor activity	0.0362	18	1317	70	-0.52	0.033	1000	-1000	-0.087	-1000
Reelin signaling pathway	0.0342	17	987	56	-0.23	0.014	1000	-1000	-0.1	-1000
Ephrin A reverse signaling	0.0322	16	118	7	-0.022	0.001	1000	-1000	-0.04	-1000
Signaling mediated by p38-alpha and p38-beta	0.0322	16	713	44	-0.18	0.014	1000	-1000	-0.073	-1000
EGFR-dependent Endothelin signaling events	0.0322	16	351	21	-0.098	0.014	1000	-1000	-0.085	-1000
ErbB2/ErbB3 signaling events	0.0302	15	980	65	-0.32	0.026	1000	-1000	-0.088	-1000
Arf6 signaling events	0.0302	15	988	62	-0.16	0.041	1000	-1000	-0.085	-1000
EPO signaling pathway	0.0302	15	874	55	-0.077	0.027	1000	-1000	-0.12	-1000
Signaling events mediated by HDAC Class III	0.0302	15	620	40	-0.2	0.075	1000	-1000	-0.056	-1000
TRAIL signaling pathway	0.0302	15	721	48	-0.085	0.016	1000	-1000	-0.085	-1000
Plasma membrane estrogen receptor signaling	0.0302	15	1372	86	-0.3	0.03	1000	-1000	-0.1	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0282	14	779	54	-0.31	0.028	1000	-1000	-0.13	-1000
Noncanonical Wnt signaling pathway	0.0282	14	378	26	-0.08	0.014	1000	-1000	-0.1	-1000
PDGFR-alpha signaling pathway	0.0282	14	653	44	-0.13	0.033	1000	-1000	-0.076	-1000
VEGFR1 specific signals	0.0282	14	823	56	-0.14	0.039	1000	-1000	-0.094	-1000
Fc-epsilon receptor I signaling in mast cells	0.0262	13	1337	97	-0.19	0.035	1000	-1000	-0.11	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0262	13	487	37	-0.083	0.014	1000	-1000	-0.065	-1000
S1P1 pathway	0.0262	13	480	36	-0.14	0.014	1000	-1000	-0.076	-1000
Signaling events mediated by PRL	0.0262	13	452	34	-0.11	0.034	1000	-1000	-0.048	-1000
Cellular roles of Anthrax toxin	0.0241	12	496	39	-0.043	0.019	1000	-1000	-0.036	-1000
Retinoic acid receptors-mediated signaling	0.0241	12	720	58	-0.18	0.031	1000	-1000	-0.089	-1000
IL6-mediated signaling events	0.0241	12	920	75	-0.11	0.063	1000	-1000	-0.11	-1000
Nectin adhesion pathway	0.0221	11	723	63	-0.14	0.04	1000	-1000	-0.092	-1000
JNK signaling in the CD4+ TCR pathway	0.0201	10	171	17	-0.039	0.036	1000	-1000	-0.074	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0201	10	521	52	-0.21	0.035	1000	-1000	-0.083	-1000
FAS signaling pathway (CD95)	0.0201	10	481	47	-0.085	0.014	1000	-1000	-0.061	-1000
IL2 signaling events mediated by PI3K	0.0201	10	586	58	-0.17	0.062	1000	-1000	-0.11	-1000
IGF1 pathway	0.0201	10	587	57	-0.089	0.021	1000	-1000	-0.11	-1000
Rapid glucocorticoid signaling	0.0201	10	204	20	-0.061	0.014	1000	-1000	-0.049	-1000
FOXM1 transcription factor network	0.0201	10	558	51	-0.36	0.16	1000	-1000	-0.21	-1000
Ras signaling in the CD4+ TCR pathway	0.0201	10	171	17	-0.026	0.029	1000	-1000	-0.053	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0181	9	429	45	-0.085	0.035	1000	-1000	-0.11	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0181	9	688	74	-0.31	0.082	1000	-1000	-0.11	-1000
S1P3 pathway	0.0181	9	397	42	-0.14	0.037	1000	-1000	-0.069	-1000
Aurora B signaling	0.0181	9	669	67	-0.32	0.031	1000	-1000	-0.079	-1000
Circadian rhythm pathway	0.0161	8	192	22	-0.14	0.051	1000	-1000	-0.072	-1000
Ceramide signaling pathway	0.0161	8	671	76	-0.094	0.034	1000	-1000	-0.075	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0141	7	209	28	-0.075	0.022	1000	-1000	-0.058	-1000
a4b1 and a4b7 Integrin signaling	0.0141	7	39	5	-0.016	0.011	1000	-1000	-0.041	-1000
Arf6 downstream pathway	0.0141	7	334	43	-0.04	0.023	1000	-1000	-0.055	-1000
HIF-2-alpha transcription factor network	0.0141	7	323	43	-0.26	0.031	1000	-1000	-0.11	-1000
Insulin Pathway	0.0141	7	528	74	-0.22	0.038	1000	-1000	-0.11	-1000
Class IB PI3K non-lipid kinase events	0.0141	7	21	3	-0.004	0.004	1000	-1000	-0.02	-1000
p38 MAPK signaling pathway	0.0141	7	339	44	-0.14	0.018	1000	-1000	-0.081	-1000
Paxillin-dependent events mediated by a4b1	0.0121	6	245	36	-0.067	0.025	1000	-1000	-0.084	-1000
IL2 signaling events mediated by STAT5	0.0121	6	151	22	-0.039	0.052	1000	-1000	-0.066	-1000
S1P4 pathway	0.0121	6	154	25	-0.034	0.023	1000	-1000	-0.071	-1000
BARD1 signaling events	0.0101	5	333	57	-0.026	0.056	1000	-1000	-0.082	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0101	5	693	125	-0.12	0.094	1000	-1000	-0.12	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0080	4	401	85	-0.07	0.058	1000	-1000	-0.093	-1000
Hedgehog signaling events mediated by Gli proteins	0.0080	4	280	65	-0.095	0.063	1000	-1000	-0.087	-1000
Aurora A signaling	0.0080	4	252	60	-0.07	0.031	1000	-1000	-0.076	-1000
Aurora C signaling	0.0080	4	28	7	-0.014	0.005	1000	-1000	-0.051	-1000
ceramide signaling pathway	0.0080	4	216	49	-0.026	0.046	1000	-1000	-0.061	-1000
Regulation of p38-alpha and p38-beta	0.0080	4	255	54	-0.1	0.037	1000	-1000	-0.087	-1000
Class I PI3K signaling events	0.0080	4	305	73	-0.1	0.04	1000	-1000	-0.083	-1000
Arf6 trafficking events	0.0080	4	289	71	-0.25	0.047	1000	-1000	-0.095	-1000
PLK1 signaling events	0.0060	3	299	85	-0.019	0.036	1000	-1000	-0.067	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0060	3	281	83	-0.082	0.066	1000	-1000	-0.096	-1000
TCGA08_rtk_signaling	0.0060	3	89	26	-0.031	0.048	1000	-1000	-0.029	-1000
E-cadherin signaling events	0.0060	3	16	5	-0.005	0.013	1000	-1000	-0.065	-1000
Canonical NF-kappaB pathway	0.0040	2	87	39	-0.029	0.086	1000	-1000	-0.1	-1000
Signaling events mediated by HDAC Class II	0.0040	2	181	75	-0.035	0.032	1000	-1000	-0.069	-1000
S1P5 pathway	0.0040	2	45	17	-0.017	0.023	1000	-1000	-0.064	-1000
E-cadherin signaling in keratinocytes	0.0040	2	98	43	-0.018	0.047	1000	-1000	-0.09	-1000
Alternative NF-kappaB pathway	0.0040	2	30	13	-0.008	0.014	1000	-1000	-0.075	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0020	1	37	23	-0.015	0.05	1000	-1000	-0.089	-1000
PLK2 and PLK4 events	0.0020	1	4	3	0.011	0.023	1000	-1000	-0.024	-1000
Insulin-mediated glucose transport	0.0020	1	37	32	-0.076	0.048	1000	-1000	-0.083	-1000
Signaling events mediated by HDAC Class I	0.0020	1	159	104	-0.13	0.061	1000	-1000	-0.081	-1000
FoxO family signaling	0.0020	1	108	64	-0.033	0.16	1000	-1000	-0.093	-1000
Atypical NF-kappaB pathway	0.0020	1	39	31	-0.006	0.048	1000	-1000	-0.056	-1000
E-cadherin signaling in the nascent adherens junction	0.0020	1	138	76	-0.016	0.06	1000	-1000	-0.11	-1000
mTOR signaling pathway	0.0000	0	41	53	-0.004	0.034	1000	-1000	-0.069	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	21	68	-0.12	0.062	1000	-1000	-0.078	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.065	-1000
Arf1 pathway	0.0000	0	9	54	-0.004	0.037	1000	-1000	-0.062	-1000
Total	NA	3122	176767	7203	-28	7	131000	-131000	-12	-131000

TCGA08_retinoblastoma

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.1	0.22	-10000	0	-0.53	102	102
CDKN2C	0.017	0.14	-10000	0	-0.75	14	14
CDKN2A	-0.35	0.4	-10000	0	-0.77	230	230
CCND2	0.13	0.13	0.22	284	-0.15	1	285
RB1	-0.14	0.14	-10000	0	-0.24	283	283
CDK4	0.15	0.14	0.25	289	-10000	0	289
CDK6	0.14	0.14	0.25	281	-10000	0	281
G1/S progression	0.13	0.14	0.24	283	-10000	0	283

×

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	0.01	0.053	-9999	-0.82	2	2
CCL5	-0.11	0.3	-9999	-0.81	76	76
SDCBP	0.014	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.46	0.19	-9999	-0.56	357	357
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.43	0.18	-9999	-0.53	357	357
Syndecan-1/Syntenin	-0.43	0.18	-9999	-0.53	357	357
MAPK3	-0.38	0.17	-9999	-0.48	333	333
HGF/MET	-0.025	0.11	-9999	-0.48	26	26
TGFB1/TGF beta receptor Type II	0.01	0.053	-9999	-0.82	2	2
BSG	0.014	0	-9999	-10000	0	0
keratinocyte migration	-0.43	0.18	-9999	-0.52	357	357
Syndecan-1/RANTES	-0.5	0.25	-9999	-0.6	376	376
Syndecan-1/CD147	-0.41	0.18	-9999	-0.51	357	357
Syndecan-1/Syntenin/PIP2	-0.42	0.17	-9999	-0.51	357	357
LAMA5	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.41	0.17	-9999	-0.5	357	357
MMP7	-0.18	0.34	-9999	-0.79	118	118
HGF	-0.012	0.13	-9999	-0.63	20	20
Syndecan-1/CASK	-0.44	0.18	-9999	-0.54	357	357
Syndecan-1/HGF/MET	-0.43	0.19	-9999	-0.52	368	368
regulation of cell adhesion	-0.37	0.16	-9999	-0.59	91	91
HPSE	0.009	0.052	-9999	-0.57	4	4
positive regulation of cell migration	-0.46	0.19	-9999	-0.56	357	357
SDC1	-0.46	0.19	-9999	-0.57	357	357
Syndecan-1/Collagen	-0.46	0.19	-9999	-0.56	357	357
PPIB	0.014	0	-9999	-10000	0	0
MET	0.005	0.083	-9999	-0.74	6	6
PRKACA	0.014	0	-9999	-10000	0	0
MMP9	-0.6	0.37	-9999	-0.82	366	366
MAPK1	-0.38	0.17	-9999	-0.48	333	333
homophilic cell adhesion	-0.46	0.19	-9999	-0.55	357	357
MMP1	-0.72	0.28	-9999	-0.82	435	435

×

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	-0.22	0.23	-9999	-0.47	221	221
Syndecan-4/Syndesmos	-0.39	0.26	-9999	-0.63	221	221
positive regulation of JNK cascade	-0.4	0.22	-9999	-0.59	254	254
Syndecan-4/ADAM12	-0.69	0.36	-9999	-0.93	319	319
CCL5	-0.11	0.3	-9999	-0.81	76	76
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.014	0	-9999	-10000	0	0
ITGA5	-0.25	0.39	-9999	-0.82	155	155
SDCBP	0.014	0	-9999	-10000	0	0
PLG	0.002	0.073	-9999	-0.8	4	4
ADAM12	-0.58	0.38	-9999	-0.82	355	355
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.12	0.062	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.56	0.34	-9999	-0.8	288	288
Syndecan-4/CXCL12/CXCR4	-0.42	0.26	-9999	-0.63	254	254
Syndecan-4/Laminin alpha3	-0.51	0.34	-9999	-0.77	266	266
MDK	-0.023	0.17	-9999	-0.81	22	22
Syndecan-4/FZD7	-0.4	0.26	-9999	-0.64	223	223
Syndecan-4/Midkine	-0.41	0.26	-9999	-0.64	234	234
FZD7	0.001	0.1	-9999	-0.79	8	8
Syndecan-4/FGFR1/FGF	-0.38	0.23	-9999	-0.58	235	235
THBS1	-0.014	0.14	-9999	-0.71	19	19
integrin-mediated signaling pathway	-0.45	0.3	-9999	-0.7	245	245
positive regulation of MAPKKK cascade	-0.4	0.22	-9999	-0.59	254	254
Syndecan-4/TACI	-0.44	0.28	-9999	-0.68	249	249
CXCR4	-0.015	0.15	-9999	-0.82	17	17
cell adhesion	-0.18	0.22	-9999	-0.4	216	216
Syndecan-4/Dynamin	-0.39	0.26	-9999	-0.63	221	221
Syndecan-4/TSP1	-0.4	0.27	-9999	-0.65	224	224
Syndecan-4/GIPC	-0.39	0.26	-9999	-0.63	221	221
Syndecan-4/RANTES	-0.46	0.3	-9999	-0.7	256	256
ITGB1	0.012	0.037	-9999	-0.82	1	1
LAMA1	-0.32	0.41	-9999	-0.81	199	199
LAMA3	-0.22	0.37	-9999	-0.82	139	139
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.092	0.071	-9999	-0.66	2	2
Syndecan-4/alpha-Actinin	-0.39	0.26	-9999	-0.63	221	221
TFPI	0.006	0.074	-9999	-0.72	5	5
F2	-0.08	0.24	-9999	-0.83	47	47
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.63	156	156
positive regulation of cell adhesion	-0.63	0.38	-9999	-0.87	315	315
ACTN1	0.012	0.037	-9999	-0.82	1	1
TNC	-0.14	0.32	-9999	-0.82	92	92
Syndecan-4/CXCL12	-0.42	0.25	-9999	-0.64	247	247
FGF6	0.003	0.005	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
CXCL12	-0.051	0.18	-9999	-0.57	55	55
TNFRSF13B	-0.082	0.26	-9999	-0.82	56	56
FGF2	-0.007	0.12	-9999	-0.63	16	16
FGFR1	0.004	0.087	-9999	-0.78	6	6
Syndecan-4/PI-4-5-P2	-0.4	0.26	-9999	-0.64	221	221
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.35	0.42	-9999	-0.81	221	221
cell migration	-0.04	0.02	-9999	-10000	0	0
PRKCD	0.027	0.011	-9999	-10000	0	0
vasculogenesis	-0.39	0.25	-9999	-0.62	224	224
SDC4	-0.42	0.27	-9999	-0.67	221	221
Syndecan-4/Tenascin C	-0.47	0.33	-9999	-0.74	245	245
Syndecan-4/PI-4-5-P2/PKC alpha	-0.093	0.048	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.39	0.26	-9999	-0.63	221	221
MMP9	-0.6	0.36	-9999	-0.81	366	366
Rac1/GTP	-0.19	0.22	-9999	-0.41	216	216
cytoskeleton organization	-0.38	0.24	-9999	-0.6	221	221
GIPC1	0.014	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.4	0.26	-9999	-0.63	224	224

×

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	0.5	-10000	0	-1.4	296	296
STAT6 (cleaved dimer)	-1.1	0.52	-10000	0	-1.4	333	333
IGHG1	-0.33	0.13	-10000	0	-0.47	97	97
IGHG3	-1	0.48	-10000	0	-1.3	328	328
AKT1	-0.4	0.18	-10000	0	-0.74	36	36
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.29	0.16	-10000	0	-0.73	25	25
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.41	0.18	-10000	0	-0.81	23	23
THY1	-1.1	0.55	-10000	0	-1.5	310	310
MYB	-0.05	0.19	-10000	0	-0.59	52	52
HMGA1	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.51	0.23	-10000	0	-0.95	45	45
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.41	0.18	-10000	0	-0.79	23	23
SP1	0.014	0.012	-10000	0	-10000	0	0
INPP5D	0.01	0.045	-10000	0	-0.57	3	3
SOCS5	0.036	0.01	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-1.1	0.52	-10000	0	-1.4	332	332
SOCS1	-0.64	0.28	-10000	0	-0.85	230	230
SOCS3	-0.42	0.2	-10000	0	-0.82	33	33
FCER2	-0.74	0.35	-10000	0	-1.2	104	104
PARP14	0.009	0.065	-10000	0	-0.82	3	3
CCL17	-1.1	0.51	-10000	0	-1.4	309	309
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.33	0.15	-10000	0	-0.73	20	20
T cell proliferation	-1.1	0.53	-10000	0	-1.4	311	311
IL4R/JAK1	-1.1	0.5	-10000	0	-1.4	309	309
EGR2	-1.1	0.5	-10000	0	-1.4	303	303
JAK2	-0.032	0.032	-10000	0	-0.61	1	1
JAK3	-0.007	0.15	-10000	0	-0.82	17	17
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
JAK1	0.001	0.006	-10000	0	-10000	0	0
COL1A2	-0.49	0.36	-10000	0	-0.94	184	184
CCL26	-1.1	0.51	-10000	0	-1.4	316	316
IL4R	-1.1	0.55	-10000	0	-1.5	308	308
PTPN6	0.035	0.007	-10000	0	-10000	0	0
IL13RA2	-1.1	0.52	-10000	0	-1.4	306	306
IL13RA1	-0.031	0.019	-10000	0	-10000	0	0
IRF4	-0.28	0.33	-10000	0	-0.94	85	85
ARG1	-0.55	0.57	-10000	0	-1.4	153	153
CBL	-0.48	0.22	-10000	0	-0.89	45	45
GTF3A	0.007	0.018	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.043	0.03	-10000	0	-0.45	1	1
IRF4/BCL6	-0.25	0.31	-10000	0	-0.88	84	84
CD40LG	-0.06	0.21	-10000	0	-0.59	65	65
MAPK14	-0.47	0.22	-10000	0	-0.89	44	44
mitosis	-0.38	0.18	-10000	0	-0.71	34	34
STAT6	-1.3	0.7	-10000	0	-1.7	325	325
SPI1	-0.017	0.075	-10000	0	-0.75	3	3
RPS6KB1	-0.36	0.17	-10000	0	-0.71	24	24
STAT6 (dimer)	-1.3	0.7	-10000	0	-1.7	325	325
STAT6 (dimer)/PARP14	-1.2	0.59	-10000	0	-1.5	322	322
mast cell activation	0.021	0.008	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.39	0.18	-10000	0	-0.82	28	28
FRAP1	-0.4	0.18	-10000	0	-0.74	36	36
LTA	-1.1	0.51	-10000	0	-1.4	315	315
FES	0.014	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	1.2	0.62	1.6	325	-10000	0	325
CCL11	-1.2	0.49	-10000	0	-1.5	339	339
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.39	0.18	-10000	0	-0.8	28	28
IL2RG	-0.006	0.15	-10000	0	-0.79	17	17
IL10	-1.1	0.5	-10000	0	-1.4	304	304
IRS1	0.01	0.045	-10000	0	-0.57	3	3
IRS2	0.011	0.037	-10000	0	-0.57	2	2
IL4	-0.2	0.073	-10000	0	-10000	0	0
IL5	-1.1	0.5	-10000	0	-1.4	299	299
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.77	0.31	-10000	0	-0.98	292	292
COL1A1	-0.67	0.38	-10000	0	-0.97	292	292
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-1.1	0.54	-10000	0	-1.5	298	298
IL2R gamma/JAK3	-0.019	0.18	-10000	0	-0.69	30	30
TFF3	-1.3	0.59	-10000	0	-1.6	349	349
ALOX15	-1.1	0.54	-10000	0	-1.5	313	313
MYBL1	-0.003	0.12	-10000	0	-0.82	10	10
T-helper 2 cell differentiation	-0.79	0.33	-10000	0	-1	303	303
SHC1	0.014	0	-10000	0	-10000	0	0
CEBPB	-0.013	0.048	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.39	0.17	-10000	0	-0.77	22	22
mol:PI-3-4-5-P3	-0.4	0.18	-10000	0	-0.74	36	36
PI3K	-0.42	0.2	-10000	0	-0.8	36	36
DOK2	0.008	0.069	-10000	0	-0.76	4	4
ETS1	0.03	0.066	-10000	0	-0.81	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.31	0.15	-10000	0	-0.7	22	22
ITGB3	-1.1	0.51	-10000	0	-1.4	295	295
PIGR	-1.4	0.61	-10000	0	-1.7	374	374
IGHE	0.052	0.045	0.27	4	-10000	0	4
MAPKKK cascade	-0.3	0.14	-10000	0	-0.68	22	22
BCL6	0.014	0.002	-10000	0	-10000	0	0
OPRM1	-1.1	0.5	-10000	0	-1.4	300	300
RETNLB	-1.1	0.51	-10000	0	-1.4	313	313
SELP	-1.1	0.55	-10000	0	-1.5	311	311
AICDA	-1	0.48	-10000	0	-1.4	306	306

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.27	0.28	-9999	-0.57	154	154
NF kappa B1 p50/RelA/I kappa B alpha	-0.28	0.24	-9999	-0.58	138	138
alphaV/beta3 Integrin/Osteopontin/Src	-0.35	0.32	-9999	-0.64	270	270
AP1	-0.32	0.32	-9999	-0.81	91	91
ILK	-0.28	0.28	-9999	-0.52	274	274
bone resorption	-0.22	0.25	-9999	-0.75	18	18
PTK2B	0.013	0.026	-9999	-0.57	1	1
PYK2/p130Cas	-0.27	0.24	-9999	-0.52	154	154
ITGAV	0.004	0.08	-9999	-0.78	5	5
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.008	0.057	-9999	-0.41	10	10
alphaV/beta3 Integrin/Osteopontin	-0.33	0.3	-9999	-0.58	274	274
MAP3K1	-0.29	0.29	-9999	-0.53	274	274
JUN	0.013	0.002	-9999	-10000	0	0
MAPK3	-0.3	0.29	-9999	-0.62	154	154
MAPK1	-0.3	0.29	-9999	-0.62	154	154
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.27	0.28	-9999	-0.55	174	174
ITGB3	-0.017	0.14	-9999	-0.73	19	19
NFKBIA	-0.29	0.29	-9999	-0.64	138	138
FOS	-0.062	0.19	-9999	-0.57	64	64
CD44	0.013	0.026	-9999	-0.57	1	1
CHUK	0.014	0	-9999	-10000	0	0
PLAU	-0.43	0.4	-9999	-0.91	159	159
NF kappa B1 p50/RelA	-0.29	0.24	-9999	-0.62	137	137
BCAR1	0.014	0	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.028	0.13	-9999	-0.59	23	23
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.28	0.29	-9999	-0.53	274	274
VAV3	-0.28	0.29	-9999	-0.57	174	174
MAP3K14	-0.3	0.29	-9999	-0.55	274	274
ROCK2	0.003	0.077	-9999	-0.57	9	9
SPP1	-0.44	0.42	-9999	-0.83	268	268
RAC1	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.27	0.25	-9999	-0.53	160	160
MMP2	-0.29	0.32	-9999	-0.82	88	88

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.69	0.48	-9999	-1.2	152	152
HDAC7	0.014	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.47	0.33	-9999	-0.9	79	79
SMAD4	0.014	0.026	-9999	-0.56	1	1
ID2	-0.69	0.48	-9999	-1.3	147	147
AP1	-0.045	0.14	-9999	-0.4	64	64
ABCG2	-0.7	0.48	-9999	-1.3	148	148
HIF1A	-0.083	0.061	-9999	-0.71	1	1
TFF3	-0.81	0.54	-9999	-1.3	211	211
GATA2	0.008	0.08	-9999	-0.77	5	5
AKT1	-0.085	0.064	-9999	-10000	0	0
response to hypoxia	-0.11	0.066	-9999	-10000	0	0
MCL1	-0.69	0.48	-9999	-1.2	147	147
NDRG1	-0.69	0.48	-9999	-1.3	146	146
SERPINE1	-0.91	0.55	-9999	-1.4	251	251
FECH	-0.69	0.48	-9999	-1.2	152	152
FURIN	-0.69	0.48	-9999	-1.2	146	146
NCOA2	-0.031	0.15	-9999	-0.57	38	38
EP300	-0.091	0.096	-9999	-0.37	9	9
HMOX1	-0.69	0.48	-9999	-1.2	161	161
BHLHE40	-0.69	0.48	-9999	-1.2	150	150
BHLHE41	-0.7	0.49	-9999	-1.3	148	148
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.067	0.058	-9999	-0.45	1	1
ENG	-0.044	0.073	-9999	-10000	0	0
JUN	0.015	0.001	-9999	-10000	0	0
RORA	-0.7	0.49	-9999	-1.3	146	146
ABCB1	-0.2	0.32	-9999	-1.4	30	30
TFRC	-0.7	0.48	-9999	-1.2	168	168
CXCR4	-0.7	0.49	-9999	-1.3	150	150
TF	-0.86	0.54	-9999	-1.3	230	230
CITED2	-0.69	0.48	-9999	-1.2	150	150
HIF1A/ARNT	-0.79	0.61	-9999	-1.4	215	215
LDHA	-0.068	0.045	-9999	-10000	0	0
ETS1	-0.69	0.48	-9999	-1.2	155	155
PGK1	-0.69	0.48	-9999	-1.2	146	146
NOS2	-0.76	0.5	-9999	-1.3	172	172
ITGB2	-0.7	0.48	-9999	-1.3	151	151
ALDOA	-0.69	0.48	-9999	-1.2	150	150
Cbp/p300/CITED2	-0.67	0.49	-9999	-1.3	130	130
FOS	-0.06	0.19	-9999	-0.56	64	64
HK2	-0.69	0.48	-9999	-1.2	150	150
SP1	0.022	0.006	-9999	-10000	0	0
GCK	-0.18	0.23	-9999	-0.82	40	40
HK1	-0.69	0.48	-9999	-1.2	151	151
NPM1	-0.69	0.48	-9999	-1.2	150	150
EGLN1	-0.69	0.48	-9999	-1.2	146	146
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.69	0.48	-9999	-1.2	146	146
SMAD3	0.014	0.026	-9999	-0.56	1	1
EDN1	-0.092	0.18	-9999	-1.4	5	5
IGFBP1	-0.7	0.49	-9999	-1.3	150	150
VEGFA	-0.4	0.3	-9999	-1	21	21
HIF1A/JAB1	-0.043	0.036	-9999	-0.53	1	1
CP	-0.81	0.54	-9999	-1.3	207	207
CXCL12	-0.72	0.5	-9999	-1.3	154	154
COPS5	0.013	0.005	-9999	-10000	0	0
SMAD3/SMAD4	-0.002	0.025	-9999	-0.4	2	2
BNIP3	-0.69	0.48	-9999	-1.2	150	150
EGLN3	-0.71	0.5	-9999	-1.3	167	167
CA9	-1	0.5	-9999	-1.3	311	311
TERT	-0.77	0.52	-9999	-1.3	189	189
ENO1	-0.69	0.48	-9999	-1.2	150	150
PFKL	-0.69	0.48	-9999	-1.2	160	160
NCOA1	0.013	0.002	-9999	-10000	0	0
ADM	-0.69	0.48	-9999	-1.2	152	152
ARNT	-0.082	0.054	-9999	-10000	0	0
HNF4A	-0.071	0.24	-9999	-0.82	48	48
ADFP	-0.7	0.48	-9999	-1.2	175	175
SLC2A1	-0.4	0.3	-9999	-1	25	25
LEP	-0.74	0.51	-9999	-1.3	173	173
HIF1A/ARNT/Cbp/p300	-0.49	0.34	-9999	-0.9	99	99
EPO	-0.4	0.32	-9999	-0.99	68	68
CREBBP	-0.09	0.092	-9999	-0.37	2	2
HIF1A/ARNT/Cbp/p300/HDAC7	-0.46	0.34	-9999	-0.95	62	62
PFKFB3	-0.69	0.48	-9999	-1.2	151	151
NT5E	-0.75	0.53	-9999	-1.3	172	172

×

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	-0.58	0.44	-10000	0	-1.2	118	118
IL23A	-0.57	0.43	-10000	0	-1.2	117	117
NF kappa B1 p50/RelA/I kappa B alpha	-0.57	0.42	-10000	0	-1	165	165
positive regulation of T cell mediated cytotoxicity	-0.63	0.48	-10000	0	-1.2	167	167
ITGA3	-0.56	0.42	-10000	0	-1.1	125	125
IL17F	-0.38	0.27	-10000	0	-0.74	93	93
IL12B	-0.077	0.24	-10000	0	-0.86	43	43
STAT1 (dimer)	-0.62	0.48	-10000	0	-1.2	154	154
CD4	-0.55	0.4	-10000	0	-1.1	123	123
IL23	-0.58	0.43	-10000	0	-1.1	129	129
IL23R	-0.085	0.091	-10000	0	-0.7	6	6
IL1B	-0.6	0.45	-10000	0	-1.2	133	133
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.75	0.44	-10000	0	-1.2	199	199
TYK2	-0.005	0.041	-10000	0	-0.86	1	1
STAT4	-0.006	0.12	-10000	0	-0.8	12	12
STAT3	0.014	0	-10000	0	-10000	0	0
IL18RAP	-0.014	0.14	-10000	0	-0.73	18	18
IL12RB1	-0.081	0.24	-10000	0	-0.84	46	46
PIK3CA	0.014	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.07	0.19	-10000	0	-0.66	47	47
IL23R/JAK2	-0.1	0.097	-10000	0	-0.74	4	4
positive regulation of chronic inflammatory response	-0.63	0.48	-10000	0	-1.2	167	167
natural killer cell activation	0.008	0.008	0.06	6	-10000	0	6
JAK2	0.002	0.028	-10000	0	-0.56	1	1
PIK3R1	0.01	0.045	-10000	0	-0.57	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	128	128
ALOX12B	-0.66	0.48	-10000	0	-1.2	168	168
CXCL1	-0.59	0.45	-10000	0	-1.2	141	141
T cell proliferation	-0.63	0.48	-10000	0	-1.2	167	167
NFKBIA	0.008	0.037	-10000	0	-0.82	1	1
IL17A	-0.29	0.22	-10000	0	-0.59	70	70
PI3K	-0.58	0.42	-10000	0	-1	176	176
IFNG	-0.033	0.046	0.13	5	-0.11	104	109
STAT3 (dimer)	-0.55	0.4	-10000	0	-1.1	130	130
IL18R1	0.01	0.047	-10000	0	-0.7	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.34	0.25	-10000	0	-0.81	49	49
IL18/IL18R	-0.008	0.13	-10000	0	-0.42	37	37
macrophage activation	-0.029	0.015	-10000	0	-0.045	83	83
TNF	-0.58	0.44	-10000	0	-1.2	129	129
STAT3/STAT4	-0.59	0.43	-10000	0	-1.1	154	154
STAT4 (dimer)	-0.61	0.47	-10000	0	-1.2	141	141
IL18	-0.01	0.11	-10000	0	-0.56	19	19
IL19	-0.69	0.52	-10000	0	-1.3	185	185
STAT5A (dimer)	-0.6	0.46	-10000	0	-1.2	136	136
STAT1	-0.033	0.19	-10000	0	-0.81	28	28
SOCS3	0.013	0.026	-10000	0	-0.57	1	1
CXCL9	-0.7	0.47	-10000	0	-1.2	204	204
MPO	-0.57	0.43	-10000	0	-1.1	134	134
positive regulation of humoral immune response	-0.63	0.48	-10000	0	-1.2	167	167
IL23/IL23R/JAK2/TYK2	-0.66	0.53	-10000	0	-1.3	158	158
IL6	-0.59	0.46	-10000	0	-1.2	129	129
STAT5A	0.014	0	-10000	0	-10000	0	0
IL2	0.006	0.038	-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	-0.56	0.41	-10000	0	-1.1	109	109
keratinocyte proliferation	-0.63	0.48	-10000	0	-1.2	167	167
NOS2	-0.61	0.44	-10000	0	-1.1	149	149

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.023	0.17	-9999	-0.81	22	22
GPC2	-0.15	0.33	-9999	-0.82	96	96
GPC2/Midkine	-0.15	0.29	-9999	-0.69	105	105
neuron projection morphogenesis	-0.14	0.29	-9999	-0.69	105	105

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.13	0.27	-9999	-0.64	98	98
alphaM/beta2 Integrin/GPIbA	-0.07	0.21	-9999	-0.71	44	44
alphaM/beta2 Integrin/proMMP-9	-0.45	0.31	-9999	-0.6	369	369
PLAUR	-0.035	0.2	-9999	-0.82	29	29
HMGB1	0.011	0.016	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.056	0.19	-9999	-0.68	38	38
AGER	-0.001	0.099	-9999	-0.82	7	7
RAP1A	0.014	0	-9999	-10000	0	0
SELPLG	0.014	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.074	0.19	-9999	-0.64	41	41
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.6	0.37	-9999	-0.82	366	366
CYR61	0.006	0.079	-9999	-0.77	5	5
TLN1	0.01	0.053	-9999	-0.82	2	2
Rap1/GTP	-0.16	0.15	-9999	-0.51	45	45
RHOA	0.014	0	-9999	-10000	0	0
P-selectin oligomer	-0.09	0.22	-9999	-0.56	89	89
MYH2	-0.35	0.24	-9999	-0.56	240	240
MST1R	0.003	0.077	-9999	-0.57	9	9
leukocyte activation during inflammatory response	-0.066	0.19	-9999	-0.57	54	54
APOB	-0.01	0.13	-9999	-0.78	13	13
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.1	0.29	-9999	-0.82	70	70
JAM3	0.012	0.037	-9999	-0.82	1	1
GP1BA	-0.014	0.14	-9999	-0.74	17	17
alphaM/beta2 Integrin/CTGF	-0.06	0.19	-9999	-0.67	40	40
alphaM/beta2 Integrin	-0.18	0.19	-9999	-0.43	144	144
JAM3 homodimer	0.012	0.037	-9999	-0.82	1	1
ICAM2	0.01	0.052	-9999	-0.65	3	3
ICAM1	-0.03	0.18	-9999	-0.82	26	26
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.18	0.19	-9999	-0.43	144	144
cell adhesion	-0.069	0.21	-9999	-0.7	44	44
NFKB1	-0.031	0.23	-9999	-0.84	21	21
THY1	-0.22	0.37	-9999	-0.82	137	137
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.024	0.11	-9999	-0.53	22	22
alphaM/beta2 Integrin/LRP/tPA	-0.063	0.19	-9999	-0.6	49	49
IL6	-0.057	0.29	-9999	-0.78	59	59
ITGB2	-0.014	0.14	-9999	-0.8	15	15
elevation of cytosolic calcium ion concentration	-0.28	0.33	-9999	-0.58	240	240
alphaM/beta2 Integrin/JAM2/JAM3	-0.056	0.18	-9999	-0.64	37	37
JAM2	0	0.089	-9999	-0.57	12	12
alphaM/beta2 Integrin/ICAM1	-0.078	0.22	-9999	-0.62	57	57
alphaM/beta2 Integrin/uPA/Plg	-0.27	0.3	-9999	-0.55	240	240
RhoA/GTP	-0.22	0.22	-9999	-0.52	134	134
positive regulation of phagocytosis	-0.14	0.17	-9999	-0.58	46	46
Ron/MSP	-0.014	0.081	-9999	-0.46	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.29	0.34	-9999	-0.59	240	240
alphaM/beta2 Integrin/uPAR	-0.084	0.24	-9999	-0.68	59	59
PLAU	-0.34	0.41	-9999	-0.82	213	213
PLAT	-0.011	0.14	-9999	-0.8	15	15
actin filament polymerization	-0.33	0.23	-9999	-0.53	240	240
MST1	0.005	0.083	-9999	-0.74	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.067	0.19	-9999	-0.58	54	54
TNF	-0.035	0.25	-9999	-0.77	37	37
RAP1B	0.012	0.037	-9999	-0.82	1	1
alphaM/beta2 Integrin/uPA	-0.28	0.32	-9999	-0.59	236	236
fibrinolysis	-0.26	0.29	-9999	-0.54	240	240
HCK	0.006	0.079	-9999	-0.77	5	5
dendritic cell antigen processing and presentation	-0.18	0.19	-9999	-0.43	144	144
VTN	-0.039	0.2	-9999	-0.82	31	31
alphaM/beta2 Integrin/CYR61	-0.059	0.19	-9999	-0.68	40	40
LPA	-0.007	0.11	-9999	-0.82	9	9
LRP1	0.013	0.026	-9999	-0.57	1	1
cell migration	-0.47	0.36	-9999	-0.63	373	373
FN1	-0.36	0.41	-9999	-0.82	221	221
alphaM/beta2 Integrin/Thy1	-0.2	0.32	-9999	-0.63	154	154
MPO	-0.01	0.12	-9999	-0.62	18	18
KNG1	-0.018	0.14	-9999	-0.82	14	14
RAP1/GDP	-0.001	0.025	-9999	-0.55	1	1
ROCK1	-0.2	0.21	-9999	-0.49	126	126
ELA2	0	0	-9999	-10000	0	0
PLG	-0.005	0.074	-9999	-0.82	4	4
CTGF	0.003	0.082	-9999	-0.63	8	8
alphaM/beta2 Integrin/Hck	-0.059	0.19	-9999	-0.67	40	40
ITGAM	-0.042	0.2	-9999	-0.81	32	32
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.1	0.2	-9999	-0.65	36	36
HP	-0.21	0.28	-9999	-0.58	185	185
leukocyte adhesion	-0.17	0.25	-9999	-0.78	44	44
SELP	-0.09	0.22	-9999	-0.57	89	89

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.27	0.31	-10000	0	-0.6	230	230
TP53	-0.078	0.087	-10000	0	-0.42	4	4
Senescence	-0.078	0.087	-10000	0	-0.42	4	4
Apoptosis	-0.078	0.087	-10000	0	-0.42	4	4
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.14	0.15	0.3	230	-10000	0	230
MDM4	0.014	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.25	0.32	-9999	-0.58	225	225
EPHB2	-0.16	0.34	-9999	-0.82	107	107
Syndecan-2/TACI	-0.066	0.21	-9999	-0.55	77	77
LAMA1	-0.32	0.41	-9999	-0.81	199	199
Syndecan-2/alpha2 ITGB1	-0.15	0.23	-9999	-0.48	154	154
HRAS	0.012	0.037	-9999	-0.82	1	1
Syndecan-2/CASK	-0.024	0.11	-9999	-0.55	22	22
ITGA5	-0.25	0.39	-9999	-0.82	155	155
BAX	0.016	0.12	-9999	-0.76	2	2
EPB41	0.014	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.022	0.1	-9999	-0.5	22	22
LAMA3	-0.22	0.37	-9999	-0.82	139	139
EZR	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.01	0.052	-9999	-0.65	3	3
Syndecan-2/MMP2	-0.077	0.25	-9999	-0.62	79	79
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.004	0.042	-9999	-0.46	4	4
dendrite morphogenesis	-0.12	0.26	-9999	-0.57	122	122
Syndecan-2/GM-CSF	-0.31	0.31	-9999	-0.57	279	279
determination of left/right symmetry	-0.007	0.13	-9999	-0.63	22	22
Syndecan-2/PKC delta	0.001	0.12	-9999	-0.54	22	22
GNB2L1	0.014	0	-9999	-10000	0	0
MAPK3	-0.28	0.28	-9999	-0.52	279	279
MAPK1	-0.28	0.28	-9999	-0.52	279	279
Syndecan-2/RACK1	-0.022	0.098	-9999	-0.47	23	23
NF1	0.014	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.007	0.13	-9999	-0.63	22	22
ITGA2	0.01	0.045	-9999	-0.57	3	3
MAPK8	0.007	0.13	-9999	-0.56	22	22
Syndecan-2/alpha2/beta1 Integrin	-0.21	0.26	-9999	-0.5	203	203
Syndecan-2/Kininogen	-0.03	0.15	-9999	-0.57	34	34
ITGB1	0.012	0.037	-9999	-0.82	1	1
SRC	0.017	0.1	-9999	-0.44	23	23
Syndecan-2/CASK/Protein 4.1	-0.022	0.1	-9999	-0.5	22	22
extracellular matrix organization	-0.001	0.12	-9999	-0.56	23	23
actin cytoskeleton reorganization	-0.25	0.31	-9999	-0.58	225	225
Syndecan-2/Caveolin-2/Ras	-0.025	0.11	-9999	-0.5	24	24
Syndecan-2/Laminin alpha3	-0.16	0.28	-9999	-0.56	154	154
Syndecan-2/RasGAP	-0.022	0.097	-9999	-0.45	23	23
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.63	156	156
PRKCD	0.014	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.12	0.26	-9999	-0.57	122	122
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	23	23
RHOA	0.014	0	-9999	-10000	0	0
SDCBP	0.014	0	-9999	-10000	0	0
TNFRSF13B	-0.082	0.26	-9999	-0.82	56	56
RASA1	0.011	0.037	-9999	-0.57	2	2
alpha2/beta1 Integrin	-0.004	0.042	-9999	-0.46	4	4
Syndecan-2/Synbindin	0.001	0.12	-9999	-0.54	22	22
TGFB1	0.01	0.053	-9999	-0.82	2	2
CASP3	0.012	0.11	-9999	-0.49	22	22
FN1	-0.36	0.41	-9999	-0.82	221	221
Syndecan-2/IL8	-0.12	0.26	-9999	-0.57	120	120
SDC2	-0.007	0.13	-9999	-0.63	22	22
KNG1	-0.018	0.14	-9999	-0.82	14	14
Syndecan-2/Neurofibromin	0.001	0.12	-9999	-0.54	22	22
TRAPPC4	0.014	0	-9999	-10000	0	0
CSF2	-0.44	0.41	-9999	-0.82	272	272
Syndecan-2/TGFB1	-0.001	0.12	-9999	-0.56	23	23
Syndecan-2/Syntenin/PI-4-5-P2	-0.022	0.1	-9999	-0.5	22	22
Syndecan-2/Ezrin	-0.021	0.1	-9999	-0.49	22	22
PRKACA	0.012	0.11	-9999	-0.49	22	22
angiogenesis	-0.12	0.26	-9999	-0.57	120	120
MMP2	-0.1	0.29	-9999	-0.82	70	70
IL8	-0.16	0.34	-9999	-0.81	106	106
calcineurin-NFAT signaling pathway	-0.066	0.21	-9999	-0.55	77	77

×

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	-0.17	0.31	-10000	0	-0.67	70	70
PTK2B	0.013	0.026	-10000	0	-0.57	1	1
mol:Ca2+	-0.055	0.21	-10000	0	-0.69	29	29
EDN1	-0.091	0.21	-10000	0	-0.41	47	47
EDN3	-0.24	0.28	-10000	0	-0.57	209	209
EDN2	-0.087	0.24	-10000	0	-0.65	75	75
HRAS/GDP	-0.05	0.18	-10000	0	-0.52	16	16
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.053	0.16	-10000	0	-0.39	34	34
ADCY4	-0.19	0.25	-10000	0	-0.62	73	73
ADCY5	-0.26	0.26	-10000	0	-0.64	108	108
ADCY6	-0.19	0.25	-10000	0	-0.6	85	85
ADCY7	-0.19	0.25	-10000	0	-0.63	72	72
ADCY1	-0.21	0.27	-10000	0	-0.66	84	84
ADCY2	-0.29	0.26	-10000	0	-0.63	134	134
ADCY3	-0.19	0.25	-10000	0	-0.63	72	72
ADCY8	-0.2	0.26	-10000	0	-0.64	82	82
ADCY9	-0.19	0.25	-10000	0	-0.63	72	72
arachidonic acid secretion	-0.077	0.21	-10000	0	-0.55	46	46
ETB receptor/Endothelin-1/Gq/GTP	-0.053	0.14	-10000	0	-0.43	29	29
GNAO1	0.008	0.069	-10000	0	-0.76	4	4
HRAS	0.011	0.038	-10000	0	-0.82	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.083	0.35	0.34	139	-0.64	66	205
ETA receptor/Endothelin-1/Gs/GTP	-0.13	0.34	0.32	115	-0.62	91	206
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.41	0.5	-10000	0	-0.85	263	263
EDNRB	-0.014	0.062	-10000	0	-0.56	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.22	0.39	-10000	0	-0.9	79	79
CYSLTR1	-0.22	0.36	-10000	0	-0.75	103	103
SLC9A1	-0.062	0.16	-10000	0	-0.33	48	48
mol:GDP	-0.06	0.18	-10000	0	-0.5	25	25
SLC9A3	-0.18	0.32	-10000	0	-0.71	103	103
RAF1	-0.079	0.19	-10000	0	-0.51	41	41
JUN	-0.038	0.18	-10000	0	-0.71	3	3
JAK2	-0.17	0.31	-10000	0	-0.67	70	70
mol:IP3	-0.071	0.17	-10000	0	-0.49	30	30
ETA receptor/Endothelin-1	-0.13	0.42	0.4	141	-0.56	203	344
PLCB1	0.01	0.037	-10000	0	-0.57	2	2
PLCB2	0.006	0.07	-10000	0	-0.76	4	4
ETA receptor/Endothelin-3	-0.23	0.24	-10000	0	-0.48	213	213
FOS	-0.12	0.34	-10000	0	-0.94	65	65
Gai/GDP	0.014	0.077	-10000	0	-0.57	3	3
CRK	0.014	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.18	0.29	-10000	0	-0.69	73	73
BCAR1	0.014	0	-10000	0	-10000	0	0
PRKCB1	-0.069	0.16	-10000	0	-0.46	31	31
GNAQ	0.014	0.006	-10000	0	-10000	0	0
GNAZ	-0.017	0.15	-10000	0	-0.74	20	20
GNAL	-0.061	0.19	-10000	0	-0.57	64	64
Gs family/GDP	-0.12	0.15	-10000	0	-0.51	35	35
ETA receptor/Endothelin-1/Gq/GTP	-0.074	0.19	-10000	0	-0.45	44	44
MAPK14	-0.028	0.12	-10000	0	-0.63	5	5
TRPC6	-0.058	0.22	-10000	0	-0.72	29	29
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.013	0.026	-10000	0	-0.57	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.13	-10000	0	-0.5	10	10
ETB receptor/Endothelin-2	-0.075	0.19	-10000	0	-0.49	79	79
ETB receptor/Endothelin-3	-0.18	0.21	-10000	0	-0.42	212	212
ETB receptor/Endothelin-1	-0.07	0.18	-10000	0	-0.66	5	5
MAPK3	-0.11	0.29	-10000	0	-0.78	67	67
MAPK1	-0.11	0.29	-10000	0	-0.78	67	67
Rac1/GDP	-0.049	0.17	-10000	0	-0.54	13	13
cAMP biosynthetic process	-0.23	0.22	-10000	0	-0.58	103	103
MAPK8	-0.056	0.2	-10000	0	-0.6	24	24
SRC	0.014	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.014	0.099	-10000	0	-0.4	10	10
p130Cas/CRK/Src/PYK2	-0.057	0.19	-10000	0	-0.59	15	15
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.051	0.18	-10000	0	-0.52	16	16
COL1A2	-0.29	0.47	-10000	0	-0.86	187	187
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.12	0.23	-10000	0	-0.56	78	78
mol:DAG	-0.071	0.17	-10000	0	-0.49	30	30
MAP2K2	-0.088	0.23	-10000	0	-0.62	50	50
MAP2K1	-0.088	0.23	-10000	0	-0.62	50	50
EDNRA	-0.084	0.21	-10000	0	-0.41	47	47
positive regulation of muscle contraction	-0.14	0.27	-10000	0	-0.66	51	51
Gq family/GDP	-0.085	0.16	-10000	0	-0.58	16	16
HRAS/GTP	-0.075	0.17	-10000	0	-0.46	40	40
PRKCH	-0.061	0.16	-10000	0	-0.47	27	27
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.063	0.16	-10000	0	-0.47	28	28
PRKCB	-0.068	0.17	-10000	0	-0.51	34	34
PRKCE	-0.061	0.16	-10000	0	-0.46	29	29
PRKCD	-0.061	0.16	-10000	0	-0.47	27	27
PRKCG	-0.12	0.21	-10000	0	-0.53	68	68
regulation of vascular smooth muscle contraction	-0.14	0.39	-10000	0	-1.1	66	66
PRKCQ	-0.068	0.17	-10000	0	-0.48	33	33
PLA2G4A	-0.085	0.23	-10000	0	-0.6	46	46
GNA14	-0.075	0.21	-10000	0	-0.57	76	76
GNA15	0.011	0.037	-10000	0	-0.57	2	2
GNA12	0.01	0.053	-10000	0	-0.82	2	2
GNA11	0.008	0.052	-10000	0	-0.57	4	4
Rac1/GTP	-0.081	0.35	0.34	140	-0.65	61	201
MMP1	-0.56	0.25	-10000	0	-0.65	435	435

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.016	0.078	-9999	-0.41	19	19
Necdin/E2F1	-0.054	0.18	-9999	-0.62	43	43
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.11	0.2	-9999	-0.48	99	99
NGF (dimer)/p75(NTR)/BEX1	-0.15	0.25	-9999	-0.57	123	123
NT-4/5 (dimer)/p75(NTR)	-0.028	0.13	-9999	-0.56	25	25
IKBKB	0.014	0	-9999	-10000	0	0
AKT1	-0.069	0.2	-9999	-0.46	96	96
IKBKG	0.014	0	-9999	-10000	0	0
BDNF	-0.036	0.18	-9999	-0.68	36	36
MGDIs/NGR/p75(NTR)/LINGO1	-0.084	0.22	-9999	-0.61	63	63
FURIN	0.014	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.067	0.16	-9999	-0.56	34	34
LINGO1	-0.048	0.22	-9999	-0.82	37	37
Sortilin/TRAF6/NRIF	-0.01	0.049	-9999	-10000	0	0
proBDNF (dimer)	-0.036	0.18	-9999	-0.68	36	36
NTRK1	-0.058	0.23	-9999	-0.82	43	43
RTN4R	-0.02	0.16	-9999	-0.82	20	20
neuron apoptosis	-0.06	0.18	-9999	-0.56	24	24
IRAK1	0.014	0	-9999	-10000	0	0
SHC1	-0.095	0.23	-9999	-0.55	96	96
ARHGDIA	0.014	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.002	0.029	-9999	-0.46	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.12	0.21	-9999	-0.51	99	99
MAGEH1	0.012	0.037	-9999	-0.82	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.12	0.22	-9999	-0.52	100	100
Mammalian IAPs/DIABLO	-0.032	0.14	-9999	-0.6	26	26
proNGF (dimer)	-0.14	0.31	-9999	-0.8	91	91
MAGED1	0.008	0.064	-9999	-0.69	4	4
APP	0.012	0.037	-9999	-0.82	1	1
NT-4/5 (dimer)	0.011	0.045	-9999	-0.69	2	2
ZNF274	0.014	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.075	0.2	-9999	-0.47	96	96
NGF	-0.14	0.32	-9999	-0.8	91	91
cell cycle arrest	-0.1	0.22	-9999	-0.51	98	98
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.029	0.13	-9999	-0.54	1	1
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.024	0.11	-9999	-0.58	15	15
NCSTN	0.014	0	-9999	-10000	0	0
mol:GTP	-0.12	0.22	-9999	-0.55	96	96
PSENEN	0.01	0.053	-9999	-0.82	2	2
mol:ceramide	-0.091	0.22	-9999	-0.5	98	98
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.009	0.1	-9999	-0.42	1	1
p75(NTR)/beta APP	-0.028	0.12	-9999	-0.53	26	26
BEX1	-0.041	0.2	-9999	-0.82	31	31
mol:GDP	-0.1	0.23	-9999	-0.52	115	115
NGF (dimer)	-0.2	0.28	-9999	-0.56	172	172
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.077	0.2	-9999	-0.56	63	63
PIK3R1	0.01	0.045	-9999	-0.57	3	3
RAC1/GTP	-0.1	0.19	-9999	-0.48	96	96
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	96	96
RHOB	0.014	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.047	0.16	-9999	-0.63	37	37
NT3 (dimer)	-0.16	0.26	-9999	-0.56	148	148
TP53	-0.013	0.15	-9999	-0.45	35	35
PRDM4	-0.092	0.22	-9999	-0.51	98	98
BDNF (dimer)	-0.47	0.32	-9999	-0.63	367	367
PIK3CA	0.014	0	-9999	-10000	0	0
SORT1	-0.008	0.11	-9999	-0.57	19	19
activation of caspase activity	-0.11	0.2	-9999	-0.47	99	99
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.12	0.21	-9999	-0.51	98	98
RHOC	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
MAPK10	-0.06	0.19	-9999	-0.54	24	24
DIABLO	0.014	0	-9999	-10000	0	0
SMPD2	-0.092	0.22	-9999	-0.51	98	98
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	98	98
PSEN1	0.014	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.018	-9999	-0.41	1	1
NT3 (dimer)/p75(NTR)	-0.15	0.22	-9999	-0.44	165	165
MAPK8	-0.05	0.19	-9999	-0.54	17	17
MAPK9	-0.047	0.18	-9999	-0.53	16	16
APAF1	0.013	0.026	-9999	-0.57	1	1
NTF3	-0.16	0.26	-9999	-0.57	148	148
NTF4	0.011	0.045	-9999	-0.69	2	2
NDN	0.003	0.077	-9999	-0.57	9	9
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.093	0.17	-9999	-0.43	96	96
p75 CTF/Sortilin/TRAF6/NRIF	-0.013	0.06	-9999	-10000	0	0
RhoA-B-C/GTP	-0.12	0.22	-9999	-0.54	96	96
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.055	0.14	-9999	-0.47	34	34
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.06	0.15	-9999	-0.51	34	34
PRKACB	0.013	0.026	-9999	-0.57	1	1
proBDNF (dimer)/p75 ECD	-0.038	0.14	-9999	-0.5	38	38
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.021	0.17	-9999	-0.82	21	21
BIRC2	-0.005	0.12	-9999	-0.82	11	11
neuron projection morphogenesis	-0.098	0.2	-9999	-0.46	97	97
BAD	-0.043	0.18	-9999	-0.52	15	15
RIPK2	0.014	0	-9999	-10000	0	0
NGFR	-0.023	0.16	-9999	-0.71	25	25
CYCS	-0.082	0.22	-9999	-0.48	98	98
ADAM17	0.011	0.037	-9999	-0.57	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.11	0.2	-9999	-0.5	96	96
BCL2L11	-0.043	0.18	-9999	-0.52	15	15
BDNF (dimer)/p75(NTR)	-0.063	0.17	-9999	-0.52	61	61
PI3K	-0.11	0.2	-9999	-0.5	96	96
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.12	0.21	-9999	-0.51	98	98
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	115	115
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.12	0.22	-9999	-0.52	98	98
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
PRKCZ	0.013	0.026	-9999	-0.57	1	1
PLG	-0.005	0.074	-9999	-0.82	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.097	0.22	-9999	-0.59	31	31
SQSTM1	0.014	0	-9999	-10000	0	0
NGFRAP1	0.01	0.053	-9999	-0.82	2	2
CASP3	-0.037	0.17	-9999	-0.47	15	15
E2F1	-0.048	0.22	-9999	-0.82	37	37
CASP9	0.014	0	-9999	-10000	0	0
IKK complex	-0.1	0.16	-9999	-0.71	6	6
NGF (dimer)/TRKA	-0.16	0.28	-9999	-0.63	129	129
MMP7	-0.18	0.34	-9999	-0.79	118	118
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.11	0.2	-9999	-0.48	98	98
MMP3	-0.54	0.39	-9999	-0.81	330	330
APAF-1/Caspase 9	-0.1	0.18	-9999	-0.71	17	17

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.011	0.037	-10000	0	-0.57	2	2
EPHB2	-0.16	0.34	-10000	0	-0.82	107	107
EFNB1	-0.025	0.17	-10000	0	-0.63	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.23	-10000	0	-0.48	144	144
Ephrin B2/EPHB1-2	-0.13	0.22	-10000	0	-0.5	123	123
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.45	144	144
Ephrin B1/EPHB1-2/Tiam1	-0.15	0.25	-10000	0	-0.51	144	144
DNM1	-0.049	0.22	-10000	0	-0.82	37	37
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.006	0.095	-10000	0	-0.59	12	12
YES1	-0.019	0.13	-10000	0	-0.83	12	12
Ephrin B1/EPHB1-2/NCK2	-0.15	0.25	-10000	0	-0.51	144	144
PI3K	0.005	0.1	-10000	0	-0.64	12	12
mol:GDP	-0.15	0.25	-10000	0	-0.51	144	144
ITGA2B	-0.065	0.24	-10000	0	-0.82	47	47
endothelial cell proliferation	-0.001	0.022	-10000	0	-0.34	2	2
FYN	-0.019	0.13	-10000	0	-0.83	12	12
MAP3K7	-0.015	0.097	-10000	0	-0.63	12	12
FGR	-0.019	0.13	-10000	0	-0.82	12	12
TIAM1	0.007	0.063	-10000	0	-0.57	6	6
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
RGS3	0.014	0	-10000	0	-10000	0	0
cell adhesion	-0.038	0.2	-10000	0	-0.51	66	66
LYN	-0.019	0.13	-10000	0	-0.83	12	12
Ephrin B1/EPHB1-2/Src Family Kinases	-0.02	0.12	-10000	0	-0.78	12	12
Ephrin B1/EPHB1-2	-0.021	0.11	-10000	0	-0.69	12	12
SRC	-0.019	0.13	-10000	0	-0.82	12	12
ITGB3	-0.015	0.14	-10000	0	-0.73	19	19
EPHB1	-0.029	0.17	-10000	0	-0.73	28	28
EPHB4	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.023	-10000	0	-0.35	2	2
alphaIIb/beta3 Integrin	-0.08	0.21	-10000	0	-0.63	63	63
BLK	-0.034	0.13	-10000	0	-0.83	12	12
HCK	-0.019	0.13	-10000	0	-0.82	12	12
regulation of stress fiber formation	0.15	0.25	0.5	144	-10000	0	144
MAPK8	0.01	0.11	-10000	0	-0.62	12	12
Ephrin B1/EPHB1-2/RGS3	-0.15	0.25	-10000	0	-0.51	144	144
endothelial cell migration	-0.01	0.084	-10000	0	-0.53	12	12
NCK2	0.014	0	-10000	0	-10000	0	0
PTPN13	-0.006	0.11	-10000	0	-0.68	12	12
regulation of focal adhesion formation	0.15	0.25	0.5	144	-10000	0	144
chemotaxis	0.15	0.25	0.5	144	-10000	0	144
PIK3CA	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.14	0.22	-10000	0	-0.47	144	144
angiogenesis	-0.021	0.1	-10000	0	-0.68	12	12
LCK	-0.021	0.13	-10000	0	-0.82	12	12

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.23	0.39	-9999	-1.1	53	53
PCK1	-0.49	0.61	-9999	-1.3	171	171
HNF4A	-0.29	0.48	-9999	-1.2	66	66
KCNJ11	-0.33	0.51	-9999	-1.1	108	108
AKT1	-0.075	0.15	-9999	-10000	0	0
response to starvation	-0.003	0.023	-9999	-10000	0	0
DLK1	-0.43	0.57	-9999	-1.1	168	168
NKX2-1	-0.088	0.34	-9999	-0.8	57	57
ACADM	-0.23	0.4	-9999	-1.1	53	53
TAT	-0.15	0.24	-9999	-0.9	15	15
CEBPB	0.015	0.004	-9999	-10000	0	0
CEBPA	0.011	0.045	-9999	-0.57	3	3
TTR	-0.29	0.33	-9999	-0.91	69	69
PKLR	-0.28	0.44	-9999	-1.1	75	75
APOA1	-0.28	0.46	-9999	-1.3	47	47
CPT1C	-0.23	0.4	-9999	-1.1	52	52
ALAS1	-0.079	0.17	-9999	-10000	0	0
TFRC	-0.2	0.3	-9999	-0.88	34	34
FOXF1	0.019	0.098	-9999	-0.72	6	6
NF1	0.022	0	-9999	-10000	0	0
HNF1A (dimer)	-0.001	0.11	-9999	-0.81	9	9
CPT1A	-0.23	0.39	-9999	-1.1	52	52
HMGCS1	-0.23	0.39	-9999	-1.1	52	52
NR3C1	0.019	0.023	-9999	-10000	0	0
CPT1B	-0.24	0.4	-9999	-1.1	55	55
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.012	0.027	-9999	-10000	0	0
GCK	-0.26	0.42	-9999	-1.1	60	60
CREB1	-0.037	0.084	-9999	-10000	0	0
IGFBP1	-0.093	0.2	-9999	-0.86	13	13
PDX1	-0.12	0.23	-9999	-0.81	22	22
UCP2	-0.23	0.4	-9999	-1.1	52	52
ALDOB	-0.26	0.44	-9999	-1.2	61	61
AFP	-0.2	0.25	-9999	-0.66	68	68
BDH1	-0.23	0.39	-9999	-1.1	53	53
HADH	-0.24	0.41	-9999	-1.1	55	55
F2	-0.3	0.47	-9999	-1.3	57	57
HNF1A	-0.001	0.11	-9999	-0.81	9	9
G6PC	-0.06	0.14	-9999	-0.71	2	2
SLC2A2	-0.13	0.22	-9999	-0.72	4	4
INS	-0.013	0.058	-9999	-0.84	2	2
FOXA1	-0.21	0.3	-9999	-0.58	189	189
FOXA3	-0.14	0.28	-9999	-0.88	54	54
FOXA2	-0.28	0.47	-9999	-1.2	64	64
ABCC8	-0.25	0.42	-9999	-1.1	57	57
ALB	-0.22	0.3	-9999	-0.74	89	89

×

Visual signal transduction: Rods

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
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.004	0.049	-9999	-0.64	3	3
Metarhodopsin II/Arrestin	-0.004	0.05	-9999	-0.56	4	4
PDE6G/GNAT1/GTP	-0.022	0.11	-9999	-0.56	20	20
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.064	-9999	-0.82	3	3
GRK1	0.001	0.037	-9999	-0.82	1	1
CNG Channel	-0.41	0.29	-9999	-0.6	303	303
mol:Na +	-0.31	0.26	-9999	-0.82	55	55
mol:ADP	0.001	0.037	-9999	-0.82	1	1
RGS9-1/Gbeta5/R9AP	-0.019	0.09	-9999	-0.54	9	9
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.32	0.28	-9999	-0.86	55	55
CNGB1	-0.43	0.41	-9999	-0.81	265	265
RDH5	0.011	0.045	-9999	-0.69	2	2
SAG	0.002	0.005	-9999	-10000	0	0
mol:Ca2+	-0.28	0.27	-9999	-0.79	54	54
Na + (4 Units)	-0.29	0.24	-9999	-0.76	54	54
RGS9	-0.004	0.12	-9999	-0.77	11	11
GNB1/GNGT1	-0.11	0.24	-9999	-0.63	85	85
GNAT1/GDP	-0.019	0.094	-9999	-0.56	10	10
GUCY2D	-0.034	0.19	-9999	-0.82	28	28
GNGT1	-0.13	0.31	-9999	-0.82	85	85
GUCY2F	0	0.052	-9999	-0.82	2	2
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.16	0.22	-9999	-0.6	54	54
mol:11-cis-retinal	0.011	0.045	-9999	-0.69	2	2
mol:cGMP	-0.066	0.2	-9999	-0.52	77	77
GNB1	0.014	0	-9999	-10000	0	0
Rhodopsin	-0.007	0.065	-9999	-0.59	6	6
SLC24A1	0.014	0	-9999	-10000	0	0
CNGA1	-0.027	0.15	-9999	-0.57	35	35
Metarhodopsin II	-0.005	0.051	-9999	-0.51	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.085	0.2	-9999	-0.54	76	76
RGS9BP	-0.001	0.089	-9999	-0.57	12	12
Metarhodopsin II/Transducin	-0.037	0.12	-9999	-0.28	91	91
GCAP Family/Ca ++	-0.058	0.16	-9999	-0.52	53	53
PDE6A/B	-0.22	0.24	-9999	-0.46	245	245
mol:Pi	-0.019	0.09	-9999	-0.54	9	9
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.089	0.19	-9999	-0.5	88	88
PDE6B	-0.045	0.2	-9999	-0.68	42	42
PDE6A	-0.25	0.29	-9999	-0.57	225	225
PDE6G	-0.015	0.15	-9999	-0.82	17	17
RHO	-0.002	0.074	-9999	-0.82	4	4
PDE6	-0.18	0.2	-9999	-0.64	42	42
GUCA1A	-0.074	0.26	-9999	-0.82	52	52
GC2/GCAP Family	-0.06	0.17	-9999	-0.52	54	54
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.006	0.074	-9999	-0.65	6	6

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.016	0.036	-9999	-10000	0	0
NFATC2	-0.063	0.13	-9999	-0.39	59	59
NFATC3	-0.016	0.036	-9999	-10000	0	0
CD40LG	-0.34	0.35	-9999	-0.85	109	109
PTGS2	-0.36	0.37	-9999	-0.88	127	127
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+	-0.017	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+	-0.018	0.014	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.004	-9999	-10000	0	0
FOSL1	-0.011	0.14	-9999	-0.8	15	15
CREM	0.014	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.17	0.16	-9999	-0.6	22	22
FOS	-0.072	0.2	-9999	-0.58	64	64
IFNG	-0.38	0.39	-9999	-0.87	146	146
AP-1/NFAT1-c-4	-0.4	0.39	-9999	-1.1	85	85
FASLG	-0.33	0.35	-9999	-0.88	94	94
NFAT1-c-4/ICER1	-0.11	0.12	-9999	-0.47	16	16
IL2RA	-0.33	0.35	-9999	-0.88	99	99
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.51	0.42	-9999	-0.82	286	286
JunB/Fra1/NFAT1-c-4	-0.11	0.14	-9999	-0.56	20	20
IL4	-0.31	0.31	-9999	-0.81	80	80
IL2	-0.01	0.035	-9999	-0.68	1	1
IL3	-0.029	0.023	-9999	-10000	0	0
FKBP1A	0.014	0	-9999	-10000	0	0
BATF3	0.007	0.074	-9999	-0.82	4	4
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.014	0.002	-9999	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	-0.015	0.13	-9999	-0.64	21	21
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.03	0.11	-9999	-0.41	36	36
STXBP1	0.014	0	-9999	-10000	0	0
ACh/CHRNA1	-0.15	0.23	-9999	-0.47	161	161
RAB3GAP2/RIMS1/UNC13B	-0.025	0.089	-9999	-0.54	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.031	0.15	-9999	-0.57	34	34
mol:ACh	-0.005	0.042	-9999	-0.12	57	57
RAB3GAP2	0.014	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.044	0.1	-9999	-0.41	10	10
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.15	0.23	-9999	-0.47	161	161
UNC13B	0.011	0.037	-9999	-0.57	2	2
CHRNA1	-0.21	0.33	-9999	-0.68	161	161
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.14	0.26	-9999	-0.58	126	126
SNAP25	-0.015	0.082	-9999	-0.3	37	37
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.2	0.36	-9999	-0.81	126	126
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.005	0.12	-9999	-0.55	21	21
STX1A/SNAP25 fragment 1/VAMP2	-0.044	0.1	-9999	-0.41	10	10

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.026	0.16	-10000	0	-0.41	26	26
CRKL	-0.024	0.15	-10000	0	-0.4	63	63
HRAS	-0.018	0.16	-10000	0	-0.56	11	11
mol:PIP3	-0.037	0.14	-10000	0	-0.4	62	62
SPRED1	0.014	0	-10000	0	-10000	0	0
SPRED2	0.011	0.037	-10000	0	-0.57	2	2
GAB1	-0.033	0.16	-10000	0	-0.43	62	62
FOXO3	-0.015	0.14	-10000	0	-0.37	62	62
AKT1	-0.026	0.15	-10000	0	-0.4	62	62
BAD	-0.015	0.14	-10000	0	-0.37	62	62
megakaryocyte differentiation	-0.043	0.17	-10000	0	-0.43	74	74
GSK3B	-0.015	0.14	-10000	0	-0.37	62	62
RAF1	-0.003	0.14	-10000	0	-0.45	9	9
SHC1	0.014	0	-10000	0	-10000	0	0
STAT3	-0.033	0.16	-10000	0	-0.43	62	62
STAT1	-0.11	0.38	-10000	0	-1	62	62
HRAS/SPRED1	-0.053	0.11	-10000	0	-0.45	9	9
cell proliferation	-0.036	0.17	-10000	0	-0.44	62	62
PIK3CA	0.014	0	-10000	0	-10000	0	0
TEC	-0.013	0.12	-10000	0	-0.57	23	23
RPS6KB1	-0.032	0.16	-10000	0	-0.42	64	64
HRAS/SPRED2	-0.054	0.11	-10000	0	-0.44	12	12
LYN/TEC/p62DOK	-0.071	0.15	-10000	0	-0.52	18	18
MAPK3	0.013	0.1	-10000	0	-0.34	4	4
STAP1	-0.066	0.19	-10000	0	-0.44	96	96
GRAP2	-0.004	0.11	-10000	0	-0.66	13	13
JAK2	-0.13	0.28	-10000	0	-0.84	62	62
STAT1 (dimer)	-0.11	0.37	-10000	0	-1	62	62
mol:Gleevec	0	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.094	0.18	-10000	0	-0.56	20	20
actin filament polymerization	-0.034	0.16	-10000	0	-0.43	63	63
LYN	0.012	0.037	-10000	0	-0.82	1	1
STAP1/STAT5A (dimer)	-0.075	0.24	-10000	0	-0.59	66	66
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
CBL/CRKL/GRB2	-0.007	0.14	-10000	0	-0.55	1	1
PI3K	-0.019	0.16	-10000	0	-0.41	62	62
PTEN	0.014	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.16	0.45	-10000	0	-1.2	64	64
MAPK8	-0.037	0.17	-10000	0	-0.45	62	62
STAT3 (dimer)	-0.032	0.16	-10000	0	-0.42	62	62
positive regulation of transcription	0.016	0.087	-10000	0	-0.28	2	2
mol:GDP	-0.078	0.15	-10000	0	-0.58	14	14
PIK3C2B	-0.033	0.16	-10000	0	-0.44	62	62
CBL/CRKL	-0.014	0.15	-10000	0	-0.38	57	57
FER	-0.034	0.16	-10000	0	-0.43	62	62
SH2B3	-0.034	0.16	-10000	0	-0.43	63	63
PDPK1	-0.027	0.14	-10000	0	-0.37	62	62
SNAI2	-0.04	0.17	-10000	0	-0.44	69	69
positive regulation of cell proliferation	-0.068	0.27	-10000	0	-0.73	63	63
KITLG	0.011	0.047	-10000	0	-0.58	3	3
cell motility	-0.068	0.27	-10000	0	-0.73	63	63
PTPN6	0.008	0.013	-10000	0	-10000	0	0
EPOR	-0.006	0.15	-10000	0	-0.68	11	11
STAT5A (dimer)	-0.05	0.22	-10000	0	-0.6	63	63
SOCS1	-0.05	0.22	-10000	0	-0.82	38	38
cell migration	0.043	0.17	0.44	71	-10000	0	71
SOS1	0.014	0	-10000	0	-10000	0	0
EPO	-0.079	0.26	-10000	0	-0.82	55	55
VAV1	0.003	0.082	-10000	0	-0.59	9	9
GRB10	-0.034	0.16	-10000	0	-0.43	63	63
PTPN11	0.014	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.043	0.17	-10000	0	-0.46	64	64
GO:0007205	0.001	0.009	-10000	0	-10000	0	0
MAP2K1	0.009	0.11	-10000	0	-0.38	4	4
CBL	0.014	0	-10000	0	-10000	0	0
KIT	-0.13	0.45	-10000	0	-1.3	63	63
MAP2K2	0.009	0.11	-10000	0	-0.36	6	6
SHC/Grb2/SOS1	-0.057	0.13	-10000	0	-0.4	56	56
STAT5A	-0.052	0.23	-10000	0	-0.62	63	63
GRB2	0.014	0	-10000	0	-10000	0	0
response to radiation	-0.039	0.17	-10000	0	-0.43	69	69
SHC/GRAP2	-0.013	0.08	-10000	0	-0.49	13	13
PTPRO	-0.045	0.17	-10000	0	-0.44	74	74
SH2B2	-0.035	0.16	-10000	0	-0.44	63	63
DOK1	0.012	0.037	-10000	0	-0.82	1	1
MATK	-0.044	0.18	-10000	0	-0.45	71	71
CREBBP	0.034	0.015	-10000	0	-10000	0	0
BCL2	-0.007	0.17	-10000	0	-1	8	8

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.23	0.28	-9999	-0.54	201	201
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.055	0.21	-9999	-0.71	46	46
SMAD9	-0.075	0.17	-9999	-0.58	44	44
SMAD4	0.013	0.026	-9999	-0.57	1	1
SMAD5	-0.049	0.14	-9999	-0.48	27	27
BMP7/USAG1	-0.16	0.24	-9999	-0.5	157	157
SMAD5/SKI	-0.039	0.14	-9999	-0.46	25	25
SMAD1	0.042	0.027	-9999	-10000	0	0
BMP2	-0.018	0.16	-9999	-0.81	19	19
SMAD1/SMAD1/SMAD4	0	0.011	-9999	-10000	0	0
BMPR1A	0.011	0.037	-9999	-0.57	2	2
BMPR1B	-0.06	0.23	-9999	-0.76	47	47
BMPR1A-1B/BAMBI	-0.062	0.16	-9999	-0.55	45	45
AHSG	-0.038	0.19	-9999	-0.82	29	29
CER1	-0.006	0.09	-9999	-0.82	6	6
BMP2-4/CER1	-0.035	0.13	-9999	-0.56	25	25
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.089	0.19	-9999	-0.54	47	47
BMP2-4 (homodimer)	-0.033	0.14	-9999	-0.56	29	29
RGMB	0.014	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.05	0.14	-9999	-0.5	43	43
RGMA	-0.053	0.19	-9999	-0.57	57	57
SMURF1	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.09	0.18	-9999	-0.5	48	48
BMP2-4/USAG1	-0.14	0.21	-9999	-0.58	52	52
SMAD6/SMURF1/SMAD5	-0.039	0.14	-9999	-0.47	22	22
SOSTDC1	-0.17	0.29	-9999	-0.62	140	140
BMP7/BMPR2/BMPR1A-1B	-0.067	0.16	-9999	-0.52	41	41
SKI	0.014	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.087	-9999	-0.78	6	6
HFE2	-0.17	0.27	-9999	-0.57	153	153
ZFYVE16	0.014	0	-9999	-10000	0	0
MAP3K7	0.014	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.045	0.15	-9999	-0.56	34	34
SMAD5/SMAD5/SMAD4	-0.039	0.14	-9999	-0.47	23	23
MAPK1	0.014	0	-9999	-10000	0	0
TAK1/TAB family	-0.092	0.13	-9999	-0.52	24	24
BMP7 (homodimer)	-0.031	0.16	-9999	-0.57	38	38
NUP214	0.014	0	-9999	-10000	0	0
BMP6/FETUA	-0.044	0.16	-9999	-0.62	35	35
SMAD1/SKI	0.048	0.026	-9999	-10000	0	0
SMAD6	0.014	0	-9999	-10000	0	0
CTDSP2	0.014	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.06	0.17	-9999	-0.56	48	48
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.36	0.41	-9999	-0.82	220	220
BMPR2 (homodimer)	0.014	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.056	0.18	-9999	-0.58	48	48
CHRDL1	-0.28	0.29	-9999	-0.57	251	251
ENDOFIN/SMAD1	0.048	0.026	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.001	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.014	0	-9999	-10000	0	0
BAMBI	-0.009	0.12	-9999	-0.68	16	16
SMURF2	0.014	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.2	0.21	-9999	-0.74	24	24
BMP2-4/GREM1	-0.27	0.29	-9999	-0.57	228	228
SMAD7	0.014	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.055	0.17	-9999	-0.53	45	45
SMAD1/SMAD6	0.048	0.026	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.031	0.16	-9999	-0.57	38	38
BMP6	0.004	0.087	-9999	-0.78	6	6
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.072	0.16	-9999	-0.44	48	48
PPM1A	0.014	0	-9999	-10000	0	0
SMAD1/SMURF2	0.048	0.026	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.014	0	-9999	-10000	0	0
PPP1CA	0.014	0	-9999	-10000	0	0
XIAP	0.014	0	-9999	-10000	0	0
CTDSP1	0.014	0	-9999	-10000	0	0
PPP1R15A	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.17	0.23	-9999	-0.51	114	114
CHRD	-0.012	0.14	-9999	-0.79	16	16
BMPR2	0.014	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.098	0.19	-9999	-0.53	48	48
BMP4	0	0.089	-9999	-0.59	11	11
FST	-0.28	0.4	-9999	-0.82	178	178
BMP2-4/NOG	-0.07	0.18	-9999	-0.58	42	42
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.062	0.15	-9999	-0.48	41	41

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.02	0.095	-10000	0	-0.55	11	11
fibroblast growth factor receptor signaling pathway	-0.02	0.095	-10000	0	-0.55	11	11
LAMA1	-0.32	0.41	-10000	0	-0.81	199	199
PRNP	0.012	0.037	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.056	0.14	-10000	0	-0.42	67	67
SMAD2	0.033	0.035	-10000	0	-0.49	1	1
GPC1/PrPc/Cu2+	-0.003	0.038	-10000	0	-0.48	3	3
GPC1/Laminin alpha1	-0.25	0.31	-10000	0	-0.63	199	199
TDGF1	-0.002	0.091	-10000	0	-0.82	6	6
CRIPTO/GPC1	-0.01	0.076	-10000	0	-0.6	8	8
APP/GPC1	-0.003	0.044	-10000	0	-0.55	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.017	0.069	-10000	0	-0.54	7	7
FLT1	0.012	0.037	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.003	0.036	-10000	0	-0.54	1	1
SERPINC1	-0.005	0.12	-10000	0	-0.82	10	10
FYN	0.016	0.073	-10000	0	-0.54	8	8
FGR	0.016	0.073	-10000	0	-0.54	8	8
positive regulation of MAPKKK cascade	0.008	0.11	-10000	0	-0.46	11	11
SLIT2	-0.064	0.2	-10000	0	-0.57	66	66
GPC1/NRG	-0.1	0.23	-10000	0	-0.61	83	83
NRG1	-0.12	0.3	-10000	0	-0.8	81	81
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.009	0.07	-10000	0	-0.54	8	8
LYN	0.016	0.073	-10000	0	-0.54	8	8
mol:Spermine	0.01	0.035	-10000	0	-0.53	2	2
cell growth	-0.02	0.095	-10000	0	-0.55	11	11
BMP signaling pathway	-0.011	0.045	0.69	2	-10000	0	2
SRC	0.017	0.069	-10000	0	-0.54	7	7
TGFBR1	0.014	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.36	0.28	-10000	0	-0.57	318	318
GPC1	0.011	0.045	-10000	0	-0.69	2	2
TGFBR1 (dimer)	0.014	0	-10000	0	-10000	0	0
VEGFA	0.004	0.091	-10000	0	-0.82	6	6
BLK	-0.061	0.2	-10000	0	-0.55	67	67
HCK	0.012	0.097	-10000	0	-0.65	9	9
FGF2	-0.007	0.12	-10000	0	-0.63	16	16
FGFR1	0.004	0.087	-10000	0	-0.78	6	6
VEGFR1 homodimer	0.012	0.037	-10000	0	-0.82	1	1
TGFBR2	0.011	0.037	-10000	0	-0.57	2	2
cell death	-0.003	0.044	-10000	0	-0.55	3	3
ATIII/GPC1	-0.015	0.094	-10000	0	-0.61	12	12
PLA2G2A/GPC1	-0.26	0.2	-10000	0	-0.41	319	319
LCK	0.003	0.11	-10000	0	-0.54	19	19
neuron differentiation	-0.1	0.23	-10000	0	-0.61	83	83
PrPc/Cu2+	-0.001	0.029	-10000	0	-0.64	1	1
APP	0.012	0.037	-10000	0	-0.82	1	1
TGFBR2 (dimer)	0.011	0.037	-10000	0	-0.56	2	2

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.27	0.23	-10000	0	-0.89	13	13
IHH	-0.054	0.075	-10000	0	-0.78	3	3
SHH Np/Cholesterol/GAS1	-0.038	0.14	-10000	0	-0.5	41	41
LRPAP1	0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.044	0.14	0.5	41	-10000	0	41
SMO/beta Arrestin2	-0.14	0.15	-10000	0	-0.57	22	22
SMO	-0.16	0.16	-10000	0	-0.61	23	23
AKT1	-0.061	0.092	-10000	0	-0.72	3	3
ARRB2	0.014	0	-10000	0	-10000	0	0
BOC	-0.039	0.17	-10000	0	-0.57	45	45
ADRBK1	0.014	0	-10000	0	-10000	0	0
heart looping	-0.15	0.16	-10000	0	-0.6	23	23
STIL	-0.13	0.16	-10000	0	-0.62	30	30
DHH N/PTCH2	-0.014	0.086	-10000	0	-0.53	13	13
DHH N/PTCH1	-0.13	0.14	-10000	0	-0.7	8	8
PIK3CA	0.014	0	-10000	0	-10000	0	0
DHH	0.009	0.053	-10000	0	-0.82	2	2
PTHLH	-0.45	0.34	-10000	0	-0.66	351	351
determination of left/right symmetry	-0.15	0.16	-10000	0	-0.6	23	23
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
skeletal system development	-0.45	0.33	-10000	0	-0.65	351	351
IHH N/Hhip	-0.055	0.17	-10000	0	-0.67	33	33
DHH N/Hhip	-0.04	0.15	-10000	0	-0.62	32	32
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.15	0.16	-10000	0	-0.6	23	23
pancreas development	-0.038	0.19	-10000	0	-0.8	30	30
HHAT	0.011	0.037	-10000	0	-0.57	2	2
PI3K	-0.002	0.031	-10000	0	-0.41	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.004	0.087	-10000	0	-0.71	7	7
somite specification	-0.15	0.16	-10000	0	-0.6	23	23
SHH Np/Cholesterol/PTCH1	-0.15	0.17	-10000	0	-0.63	33	33
SHH Np/Cholesterol/PTCH2	-0.041	0.16	-10000	0	-0.54	39	39
SHH Np/Cholesterol/Megalin	-0.06	0.19	-10000	0	-0.56	56	56
SHH	-0.031	0.17	-10000	0	-0.62	39	39
catabolic process	-0.16	0.15	-10000	0	-0.65	10	10
SMO/Vitamin D3	-0.15	0.17	-10000	0	-0.64	31	31
SHH Np/Cholesterol/Hhip	-0.063	0.19	-10000	0	-0.57	57	57
LRP2	-0.032	0.18	-10000	0	-0.82	26	26
receptor-mediated endocytosis	-0.17	0.17	-10000	0	-0.65	37	37
SHH Np/Cholesterol/BOC	-0.061	0.16	-10000	0	-0.51	38	38
SHH Np/Cholesterol/CDO	-0.039	0.14	-10000	0	-0.5	38	38
mesenchymal cell differentiation	0.067	0.19	0.56	57	-10000	0	57
mol:Vitamin D3	-0.14	0.17	-10000	0	-0.63	33	33
IHH N/PTCH2	-0.024	0.097	-10000	0	-0.57	14	14
CDON	0	0.089	-10000	0	-0.57	12	12
IHH N/PTCH1	-0.16	0.15	-10000	0	-0.66	10	10
Megalin/LRPAP1	-0.033	0.14	-10000	0	-0.63	26	26
PTCH2	-0.002	0.1	-10000	0	-0.68	11	11
SHH Np/Cholesterol	-0.036	0.14	-10000	0	-0.5	39	39
PTCH1	-0.16	0.15	-10000	0	-0.66	10	10
HHIP	-0.038	0.19	-10000	0	-0.8	30	30

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.12	0.33	-10000	0	-0.92	68	68
NFATC2	-0.041	0.23	-10000	0	-0.73	28	28
NFATC3	-0.01	0.062	-10000	0	-10000	0	0
CD40LG	-0.37	0.41	-10000	0	-1.1	67	67
ITCH	0.016	0.093	-10000	0	-10000	0	0
CBLB	0.016	0.093	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.35	0.45	-10000	0	-1.2	98	98
JUNB	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.037	0.095	-10000	0	-10000	0	0
T cell anergy	-0.009	0.16	-10000	0	-0.54	15	15
TLE4	-0.01	0.17	-10000	0	-0.65	14	14
Jun/NFAT1-c-4/p21SNFT	-0.17	0.23	-10000	0	-0.99	14	14
AP-1/NFAT1-c-4	-0.38	0.44	-10000	0	-1.1	71	71
IKZF1	-0.02	0.2	-10000	0	-0.78	18	18
T-helper 2 cell differentiation	-0.075	0.23	-10000	0	-0.79	23	23
AP-1/NFAT1	-0.14	0.18	-10000	0	-0.64	31	31
CALM1	0.006	0.061	-10000	0	-10000	0	0
EGR2	-0.066	0.29	-10000	0	-1.4	14	14
EGR3	-0.057	0.26	-10000	0	-1.3	11	11
NFAT1/FOXP3	-0.14	0.34	-10000	0	-0.8	87	87
EGR1	-0.014	0.12	-10000	0	-0.57	24	24
JUN	-0.02	0.035	-10000	0	-10000	0	0
EGR4	-0.089	0.27	-10000	0	-0.8	62	62
mol:Ca2+	-0.009	0.065	-10000	0	-10000	0	0
GBP3	-0.027	0.21	-10000	0	-0.73	25	25
FOSL1	-0.011	0.14	-10000	0	-0.8	15	15
NFAT1-c-4/MAF/IRF4	-0.12	0.24	-10000	0	-0.96	16	16
DGKA	-0.009	0.16	-10000	0	-0.61	14	14
CREM	0.013	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.22	0.26	-10000	0	-0.95	26	26
CTLA4	-0.18	0.43	-10000	0	-1	87	87
NFAT1-c-4 (dimer)/EGR1	-0.11	0.24	-10000	0	-1	16	16
NFAT1-c-4 (dimer)/EGR4	-0.16	0.28	-10000	0	-0.92	31	31
FOS	-0.097	0.19	-10000	0	-0.59	64	64
IFNG	-0.23	0.35	-10000	0	-0.82	92	92
T cell activation	-0.11	0.2	-10000	0	-0.73	10	10
MAF	0.008	0.058	-10000	0	-0.57	5	5
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.042	0.16	0.74	8	-10000	0	8
TNF	-0.14	0.32	-10000	0	-0.97	37	37
FASLG	-0.13	0.38	-10000	0	-1.3	31	31
TBX21	-0.044	0.19	-10000	0	-0.78	29	29
BATF3	0.007	0.074	-10000	0	-0.82	4	4
PRKCQ	-0.001	0.095	-10000	0	-0.61	11	11
PTPN1	-0.009	0.16	-10000	0	-0.62	12	12
NFAT1-c-4/ICER1	-0.1	0.21	-10000	0	-0.94	14	14
GATA3	-0.016	0.15	-10000	0	-0.78	19	19
T-helper 1 cell differentiation	-0.21	0.35	-10000	0	-0.81	92	92
IL2RA	-0.31	0.38	-10000	0	-1	94	94
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.009	0.16	-10000	0	-0.7	5	5
E2F1	-0.041	0.22	-10000	0	-0.81	37	37
PPARG	-0.21	0.28	-10000	0	-0.57	194	194
SLC3A2	-0.009	0.16	-10000	0	-0.65	9	9
IRF4	-0.039	0.2	-10000	0	-0.75	34	34
PTGS2	-0.39	0.45	-10000	0	-1.1	89	89
CSF2	-0.56	0.51	-10000	0	-1.1	201	201
JunB/Fra1/NFAT1-c-4	-0.1	0.22	-10000	0	-0.96	14	14
IL4	-0.078	0.24	-10000	0	-0.84	22	22
IL5	-0.34	0.38	-10000	0	-1	55	55
IL2	-0.11	0.2	-10000	0	-0.75	9	9
IL3	-0.065	0.051	-10000	0	-10000	0	0
RNF128	-0.04	0.23	-10000	0	-0.64	66	66
NFATC1	-0.042	0.16	-10000	0	-0.74	8	8
CDK4	0.025	0.14	0.65	3	-10000	0	3
PTPRK	-0.009	0.16	-10000	0	-0.65	9	9
IL8	-0.42	0.46	-10000	0	-1.1	119	119
POU2F1	0.014	0.002	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.09	0.23	-10000	0	-0.62	51	51
TBX21	-0.15	0.47	-10000	0	-1.2	55	55
B2M	0.012	0.01	-10000	0	-10000	0	0
TYK2	0.016	0.044	-10000	0	-0.84	1	1
IL12RB1	-0.059	0.25	-10000	0	-0.84	46	46
GADD45B	-0.064	0.31	-10000	0	-0.81	30	30
IL12RB2	-0.13	0.32	-10000	0	-0.79	92	92
GADD45G	-0.075	0.33	-10000	0	-0.86	36	36
natural killer cell activation	0.006	0.025	-10000	0	-10000	0	0
RELB	0.004	0.091	-10000	0	-0.82	6	6
RELA	0.014	0	-10000	0	-10000	0	0
IL18	-0.006	0.11	-10000	0	-0.57	19	19
IL2RA	-0.063	0.24	-10000	0	-0.82	46	46
IFNG	-0.17	0.34	-10000	0	-0.82	108	108
STAT3 (dimer)	-0.086	0.34	-10000	0	-0.83	51	51
HLA-DRB5	-0.007	0.12	-10000	0	-0.7	14	14
FASLG	-0.16	0.49	-10000	0	-1.2	62	62
NF kappa B2 p52/RelB	-0.22	0.37	-10000	0	-1	69	69
CD4	0.01	0.046	-10000	0	-0.7	2	2
SOCS1	-0.05	0.22	-10000	0	-0.82	38	38
EntrezGene:6955	-0.004	0.015	-10000	0	-10000	0	0
CD3D	-0.014	0.14	-10000	0	-0.73	17	17
CD3E	-0.007	0.12	-10000	0	-0.77	12	12
CD3G	-0.028	0.16	-10000	0	-0.66	29	29
IL12Rbeta2/JAK2	-0.088	0.25	-10000	0	-0.61	91	91
CCL3	-0.14	0.45	-10000	0	-1.2	57	57
CCL4	-0.14	0.45	-10000	0	-1.2	52	52
HLA-A	0.002	0.087	-10000	0	-0.78	6	6
IL18/IL18R	0.024	0.14	-10000	0	-0.46	28	28
NOS2	-0.15	0.44	-10000	0	-1	65	65
IL12/IL12R/TYK2/JAK2/SPHK2	-0.067	0.21	-10000	0	-0.6	37	37
IL1R1	-0.13	0.42	-10000	0	-1.1	51	51
IL4	-0.004	0.025	-10000	0	-10000	0	0
JAK2	0.016	0.034	-10000	0	-0.59	1	1
EntrezGene:6957	-0.004	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.1	0.34	-10000	0	-0.82	68	68
RAB7A	-0.039	0.28	-10000	0	-0.74	19	19
lysosomal transport	-0.035	0.27	-10000	0	-0.7	19	19
FOS	-0.17	0.48	-10000	0	-1.2	74	74
STAT4 (dimer)	-0.087	0.37	-10000	0	-0.93	48	48
STAT5A (dimer)	-0.28	0.44	-10000	0	-1.1	93	93
GZMA	-0.16	0.5	-10000	0	-1.3	66	66
GZMB	-0.17	0.5	-10000	0	-1.2	78	78
HLX	0.009	0.064	-10000	0	-0.82	3	3
LCK	-0.15	0.48	-10000	0	-1.2	63	63
TCR/CD3/MHC II/CD4	-0.032	0.19	-10000	0	-0.59	34	34
IL2/IL2R	-0.069	0.2	-10000	0	-0.57	59	59
MAPK14	-0.064	0.32	-10000	0	-0.82	35	35
CCR5	-0.086	0.36	-10000	0	-1	35	35
IL1B	-0.069	0.26	-10000	0	-0.8	53	53
STAT6	-0.012	0.12	-10000	0	-10000	0	0
STAT4	-0.006	0.12	-10000	0	-0.8	12	12
STAT3	0.014	0	-10000	0	-10000	0	0
STAT1	-0.033	0.19	-10000	0	-0.81	28	28
NFKB1	0.014	0	-10000	0	-10000	0	0
NFKB2	0.014	0	-10000	0	-10000	0	0
IL12B	-0.054	0.24	-10000	0	-0.83	43	43
CD8A	-0.058	0.22	-10000	0	-0.75	46	46
CD8B	-0.069	0.24	-10000	0	-0.74	54	54
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.089	0.23	0.61	51	-10000	0	51
IL2RB	0.003	0.094	-10000	0	-0.78	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.074	0.34	-10000	0	-0.83	48	48
IL2RG	-0.014	0.15	-10000	0	-0.79	17	17
IL12	-0.046	0.21	-10000	0	-0.6	61	61
STAT5A	0.014	0	-10000	0	-10000	0	0
CD247	-0.023	0.16	-10000	0	-0.8	21	21
IL2	0.003	0.037	-10000	0	-0.82	1	1
SPHK2	0.014	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.008	0.13	-10000	0	-0.64	19	19
IL12/IL12R/TYK2/JAK2	-0.17	0.52	-10000	0	-1.3	67	67
MAP2K3	-0.064	0.32	-10000	0	-0.8	38	38
RIPK2	0.014	0	-10000	0	-10000	0	0
MAP2K6	-0.076	0.33	-10000	0	-0.83	41	41
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.045	-10000	0	-0.57	3	3
IL18RAP	-0.01	0.14	-10000	0	-0.73	18	18
IL12Rbeta1/TYK2	-0.036	0.2	-10000	0	-0.65	47	47
EOMES	-0.085	0.27	-10000	0	-0.68	74	74
STAT1 (dimer)	-0.14	0.39	-10000	0	-0.88	78	78
T cell proliferation	-0.033	0.28	0.42	1	-0.66	35	36
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.014	0.048	-10000	0	-0.71	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.15	0.23	-10000	0	-0.73	39	39
ATF2	-0.051	0.3	-10000	0	-0.77	33	33

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.015	0.065	0.35	3	-10000	0	3
SMARCC2	0.015	0.007	-10000	0	-10000	0	0
SMARCC1	0.015	0.007	-10000	0	-10000	0	0
TBX21	-0.099	0.24	-10000	0	-0.87	34	34
SUMO2	0.014	0.009	-10000	0	-10000	0	0
STAT1 (dimer)	-0.023	0.19	-10000	0	-0.8	28	28
FKBP4	0.014	0	-10000	0	-10000	0	0
FKBP5	0.01	0.052	-10000	0	-0.65	3	3
GR alpha/HSP90/FKBP51/HSP90	0.098	0.099	0.35	14	-0.56	1	15
PRL	-0.1	0.17	-10000	0	-0.66	13	13
cortisol/GR alpha (dimer)/TIF2	0.18	0.23	0.58	63	-10000	0	63
RELA	-0.003	0.091	-10000	0	-10000	0	0
FGG	0.11	0.27	0.55	29	-0.66	34	63
GR beta/TIF2	0.068	0.15	0.37	18	-0.37	11	29
IFNG	-0.37	0.34	-10000	0	-0.88	129	129
apoptosis	0.026	0.18	0.55	10	-0.63	5	15
CREB1	0.017	0.018	-10000	0	-10000	0	0
histone acetylation	0.001	0.12	0.43	4	-0.45	8	12
BGLAP	-0.052	0.14	-10000	0	-0.74	9	9
GR/PKAc	0.098	0.089	0.39	5	-10000	0	5
NF kappa B1 p50/RelA	-0.013	0.16	-10000	0	-0.47	10	10
SMARCD1	0.015	0.007	-10000	0	-10000	0	0
MDM2	0.083	0.084	0.31	20	-10000	0	20
GATA3	-0.012	0.15	-10000	0	-0.78	19	19
AKT1	0	0.001	-10000	0	-10000	0	0
CSF2	-0.32	0.29	-10000	0	-0.57	257	257
GSK3B	0.014	0.009	-10000	0	-10000	0	0
NR1I3	0.054	0.18	0.56	6	-0.77	3	9
CSN2	0.13	0.15	0.47	13	-0.54	2	15
BRG1/BAF155/BAF170/BAF60A	0.038	0.027	-10000	0	-10000	0	0
NFATC1	0.015	0.003	-10000	0	-10000	0	0
POU2F1	0.015	0.016	-10000	0	-10000	0	0
CDKN1A	0.031	0.037	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	-10000	0	-10000	0	0
SFN	0.006	0.074	-10000	0	-0.72	5	5
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.096	0.1	0.37	6	-0.45	3	9
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.029	0.24	0.55	5	-0.85	24	29
JUN	-0.22	0.18	-10000	0	-0.65	37	37
IL4	-0.07	0.12	-10000	0	-0.57	5	5
CDK5R1	0.01	0.053	-10000	0	-0.82	2	2
PRKACA	0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.16	0.31	-10000	0	-0.64	78	78
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.1	0.095	0.38	7	-0.51	1	8
cortisol/GR alpha (monomer)	0.25	0.27	0.68	84	-10000	0	84
NCOA2	-0.031	0.15	-10000	0	-0.57	38	38
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.19	-10000	0	-0.63	64	64
AP-1/NFAT1-c-4	-0.41	0.27	-10000	0	-0.8	107	107
AFP	-0.16	0.2	-10000	0	-0.84	28	28
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.12	0.16	0.47	21	-0.47	1	22
TP53	0.033	0.052	-10000	0	-0.55	4	4
PPP5C	0.014	0	-10000	0	-10000	0	0
KRT17	-0.4	0.38	-10000	0	-0.93	149	149
KRT14	-0.23	0.37	-10000	0	-1.1	69	69
TBP	0.021	0.024	-10000	0	-10000	0	0
CREBBP	0.074	0.084	0.35	7	-10000	0	7
HDAC1	0.012	0.01	-10000	0	-10000	0	0
HDAC2	0.045	0.031	-10000	0	-10000	0	0
AP-1	-0.42	0.27	-10000	0	-0.81	108	108
MAPK14	0.014	0.008	-10000	0	-10000	0	0
MAPK10	-0.02	0.14	-10000	0	-0.6	28	28
MAPK11	0.014	0.009	-10000	0	-10000	0	0
KRT5	-0.27	0.25	-10000	0	-0.84	39	39
interleukin-1 receptor activity	0.031	0.031	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	-0.023	0.19	-10000	0	-0.8	28	28
CGA	-0.065	0.14	-10000	0	-0.69	8	8
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.26	0.2	0.42	262	-10000	0	262
MAPK3	0.014	0.009	-10000	0	-10000	0	0
MAPK1	0.014	0.008	-10000	0	-10000	0	0
ICAM1	-0.14	0.25	-10000	0	-0.71	52	52
NFKB1	-0.003	0.091	-10000	0	-10000	0	0
MAPK8	-0.17	0.17	-10000	0	-0.56	44	44
MAPK9	0.014	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.018	0.19	0.55	10	-0.66	5	15
BAX	0.031	0.037	-10000	0	-10000	0	0
POMC	-0.17	0.32	-10000	0	-0.92	56	56
EP300	0.074	0.09	0.34	8	-0.44	2	10
cortisol/GR alpha (dimer)/p53	0.23	0.23	0.6	73	-0.52	1	74
proteasomal ubiquitin-dependent protein catabolic process	0.057	0.064	0.28	4	-10000	0	4
SGK1	0.12	0.13	-10000	0	-1.2	2	2
IL13	-0.22	0.2	-10000	0	-0.89	19	19
IL6	-0.18	0.34	-10000	0	-1	60	60
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.19	0.16	-10000	0	-0.73	16	16
IL2	-0.27	0.2	-10000	0	-0.67	56	56
CDK5	0.014	0.005	-10000	0	-10000	0	0
PRKACB	0.013	0.026	-10000	0	-0.57	1	1
HSP90AA1	0.014	0	-10000	0	-10000	0	0
IL8	-0.22	0.34	-10000	0	-0.77	118	118
CDK5R1/CDK5	0.002	0.043	-10000	0	-0.63	2	2
NF kappa B1 p50/RelA/PKAc	0.015	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.22	0.21	0.57	63	-10000	0	63
SMARCA4	0.015	0.007	-10000	0	-10000	0	0
chromatin remodeling	0.15	0.13	0.41	40	-10000	0	40
NF kappa B1 p50/RelA/Cbp	0.074	0.16	0.42	17	-10000	0	17
JUN (dimer)	-0.22	0.18	-10000	0	-0.65	37	37
YWHAH	0.014	0	-10000	0	-10000	0	0
VIPR1	-0.088	0.22	-10000	0	-0.81	30	30
NR3C1	0.14	0.16	0.49	49	-10000	0	49
NR4A1	-0.026	0.13	-10000	0	-0.53	16	16
TIF2/SUV420H1	-0.031	0.11	-10000	0	-0.41	38	38
MAPKKK cascade	0.026	0.18	0.55	10	-0.63	5	15
cortisol/GR alpha (dimer)/Src-1	0.23	0.22	0.59	74	-10000	0	74
PBX1	-0.09	0.22	-10000	0	-0.57	90	90
POU1F1	0.003	0.017	-10000	0	-10000	0	0
SELE	-0.22	0.4	-10000	0	-1.1	78	78
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.13	0.42	40	-10000	0	40
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.22	0.21	0.57	63	-10000	0	63
mol:cortisol	0.13	0.17	0.4	92	-0.23	1	93
MMP1	-0.64	0.24	-10000	0	-0.72	435	435

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.04	0.056	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.1	0.14	-9999	-0.45	36	36
JUN	-0.066	0.16	-9999	-0.47	37	37
HRAS	0.012	0.037	-9999	-0.82	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.25	-9999	-0.61	90	90
RAP1A	0.014	0	-9999	-10000	0	0
FRS2	0.007	0.074	-9999	-0.82	4	4
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.25	-9999	-0.61	90	90
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	47	47
RHOA	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.22	-9999	-0.55	89	89
GRB7	0.005	0.083	-9999	-0.74	6	6
RET51/GFRalpha1/GDNF	-0.17	0.25	-9999	-0.61	89	89
MAPKKK cascade	-0.13	0.19	-9999	-0.62	35	35
BCAR1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.2	-9999	-0.6	45	45
lamellipodium assembly	-0.096	0.13	-9999	-0.41	36	36
RET51/GFRalpha1/GDNF/SHC	-0.17	0.25	-9999	-0.61	89	89
PIK3CA	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.12	0.2	-9999	-0.6	44	44
RET9/GFRalpha1/GDNF/Shank3	-0.12	0.2	-9999	-0.6	44	44
MAPK3	-0.11	0.23	-9999	-0.68	34	34
DOK1	0.012	0.037	-9999	-0.82	1	1
DOK6	-0.003	0.11	-9999	-0.67	12	12
PXN	0.014	0	-9999	-10000	0	0
neurite development	-0.092	0.22	-9999	-0.63	33	33
DOK5	-0.018	0.14	-9999	-0.61	25	25
GFRA1	-0.13	0.25	-9999	-0.57	120	120
MAPK8	-0.077	0.17	-9999	-0.5	37	37
HRAS/GTP	-0.15	0.22	-9999	-0.71	35	35
tube development	-0.11	0.19	-9999	-0.57	44	44
MAPK1	-0.11	0.23	-9999	-0.68	34	34
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.063	0.15	-9999	-0.53	16	16
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
PDLIM7	0.007	0.074	-9999	-0.82	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.16	0.24	-9999	-0.57	97	97
SHC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.25	-9999	-0.61	89	89
RET51/GFRalpha1/GDNF/Dok5	-0.18	0.26	-9999	-0.62	103	103
PRKCA	0.011	0.045	-9999	-0.69	2	2
HRAS/GDP	-0.001	0.029	-9999	-0.64	1	1
CREB1	-0.077	0.17	-9999	-0.49	34	34
PIK3R1	0.01	0.045	-9999	-0.57	3	3
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.06	0.15	-9999	-0.52	15	15
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.25	-9999	-0.62	94	94
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.074	0.25	-9999	-0.78	55	55
DOK4	0.014	0	-9999	-10000	0	0
JNK cascade	-0.064	0.16	-9999	-0.46	37	37
RET9/GFRalpha1/GDNF/FRS2	-0.12	0.2	-9999	-0.6	48	48
SHANK3	0.014	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.57	2	2
NCK1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.061	0.15	-9999	-0.52	15	15
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.088	0.18	-9999	-0.52	36	36
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.087	0.17	-9999	-0.52	34	34
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.089	0.18	-9999	-0.57	34	34
PI3K	-0.1	0.24	-9999	-0.67	36	36
SOS1	0.014	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.11	0.19	-9999	-0.57	44	44
GRB10	0.012	0.037	-9999	-0.82	1	1
activation of MAPKK activity	-0.083	0.17	-9999	-0.51	36	36
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.25	-9999	-0.62	92	92
GAB1	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.57	3	3
IRS2	0.011	0.037	-9999	-0.57	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.089	0.18	-9999	-0.57	34	34
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.25	-9999	-0.61	91	91
GRB2	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GDNF	-0.061	0.23	-9999	-0.82	43	43
RAC1	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.25	-9999	-0.61	89	89
Rac1/GTP	-0.11	0.16	-9999	-0.5	36	36
RET9/GFRalpha1/GDNF	-0.13	0.22	-9999	-0.44	148	148
GFRalpha1/GDNF	-0.15	0.25	-9999	-0.51	148	148

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.068	0.16	-10000	0	-0.56	38	38
FYN	-0.038	0.23	-10000	0	-0.69	43	43
LAT/GRAP2/SLP76	-0.055	0.2	-10000	0	-0.6	43	43
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.013	0.16	-10000	0	-0.47	39	39
B2M	0.014	0.005	-10000	0	-10000	0	0
IKBKG	-0.019	0.043	-10000	0	-0.17	7	7
MAP3K8	0.01	0.045	-10000	0	-0.57	3	3
mol:Ca2+	-0.036	0.039	-10000	0	-0.11	33	33
integrin-mediated signaling pathway	-0.002	0.027	-10000	0	-0.34	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.037	0.23	-10000	0	-0.69	42	42
TRPV6	-0.27	0.29	-10000	0	-0.58	233	233
CD28	-0.014	0.15	-10000	0	-0.79	17	17
SHC1	-0.042	0.23	-10000	0	-0.68	45	45
receptor internalization	-0.043	0.24	-10000	0	-0.68	50	50
PRF1	-0.06	0.29	-10000	0	-0.9	47	47
KRAS	0.01	0.053	-10000	0	-0.82	2	2
GRB2	0.014	0	-10000	0	-10000	0	0
COT/AKT1	-0.001	0.13	-10000	0	-0.38	35	35
LAT	-0.05	0.26	-10000	0	-0.73	47	47
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.011	0.14	-10000	0	-0.73	17	17
CD3E	-0.005	0.12	-10000	0	-0.77	12	12
CD3G	-0.026	0.16	-10000	0	-0.66	29	29
RASGRP2	0.007	0.023	-10000	0	-0.12	6	6
RASGRP1	-0.01	0.17	-10000	0	-0.46	44	44
HLA-A	0.004	0.087	-10000	0	-0.77	6	6
RASSF5	0.01	0.045	-10000	0	-0.57	3	3
RAP1A/GTP/RAPL	-0.002	0.027	-10000	0	-0.35	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.058	-10000	0	-0.12	22	22
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.038	0.075	-10000	0	-0.27	20	20
PRKCA	-0.013	0.097	-10000	0	-0.31	23	23
GRAP2	-0.004	0.11	-10000	0	-0.66	13	13
mol:IP3	0.034	0.19	0.23	171	-0.47	30	201
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.04	0.22	-10000	0	-0.6	53	53
ORAI1	0.15	0.16	0.32	233	-10000	0	233
CSK	-0.045	0.24	-10000	0	-0.7	45	45
B7 family/CD28	-0.17	0.28	-10000	0	-0.8	59	59
CHUK	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.061	0.27	-10000	0	-0.8	47	47
PTPN6	-0.049	0.24	-10000	0	-0.73	42	42
VAV1	-0.045	0.24	-10000	0	-0.71	45	45
Monovalent TCR/CD3	-0.021	0.17	-10000	0	-0.6	31	31
CBL	0.014	0	-10000	0	-10000	0	0
LCK	-0.046	0.25	-10000	0	-0.74	43	43
PAG1	-0.046	0.24	-10000	0	-0.69	47	47
RAP1A	0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.063	0.27	-10000	0	-0.79	47	47
CD80	-0.19	0.36	-10000	0	-0.82	122	122
CD86	0.012	0.037	-10000	0	-0.82	1	1
PDK1/CARD11/BCL10/MALT1	-0.046	0.091	-10000	0	-0.31	27	27
HRAS	0.012	0.037	-10000	0	-0.82	1	1
GO:0035030	-0.092	0.25	-10000	0	-0.64	57	57
CD8A	-0.056	0.22	-10000	0	-0.75	46	46
CD8B	-0.066	0.24	-10000	0	-0.73	54	54
PTPRC	-0.005	0.11	-10000	0	-0.69	13	13
PDK1/PKC theta	-0.015	0.2	-10000	0	-0.58	39	39
CSK/PAG1	-0.04	0.23	-10000	0	-0.68	44	44
SOS1	0.014	0	-10000	0	-10000	0	0
peptide-MHC class I	0.012	0.067	-10000	0	-0.59	6	6
GRAP2/SLP76	-0.067	0.22	-10000	0	-0.69	42	42
STIM1	0.076	0.078	-10000	0	-10000	0	0
RAS family/GTP	0.023	0.074	-10000	0	-0.18	17	17
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.048	0.26	-10000	0	-0.73	50	50
mol:DAG	-0.016	0.14	-10000	0	-0.42	30	30
RAP1A/GDP	0.012	0.025	-10000	0	-10000	0	0
PLCG1	0.014	0	-10000	0	-10000	0	0
CD247	-0.02	0.16	-10000	0	-0.79	21	21
cytotoxic T cell degranulation	-0.055	0.28	-10000	0	-0.85	47	47
RAP1A/GTP	-0.002	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.19	-10000	0	-0.56	41	41
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.016	0.23	0.26	122	-0.64	30	152
NRAS	0.014	0	-10000	0	-10000	0	0
ZAP70	-0.026	0.18	-10000	0	-0.78	25	25
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.05	0.19	-10000	0	-0.62	37	37
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.014	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.088	0.29	-10000	0	-0.72	73	73
CARD11	-0.037	0.2	-10000	0	-0.8	31	31
PRKCB	-0.015	0.11	-10000	0	-0.35	24	24
PRKCE	-0.012	0.096	-10000	0	-0.29	28	28
PRKCQ	-0.028	0.22	-10000	0	-0.65	44	44
LCP2	0.009	0.064	-10000	0	-0.82	3	3
BCL10	0.014	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.006	0.14	-10000	0	-0.4	38	38
IKK complex	0.032	0.054	-10000	0	-0.13	5	5
RAS family/GDP	-0.004	0.01	-10000	0	-0.087	2	2
MAP3K14	0.01	0.11	-10000	0	-0.31	18	18
PDPK1	-0.008	0.16	-10000	0	-0.45	36	36
TCR/CD3/MHC I/CD8/Fyn	-0.055	0.27	-10000	0	-0.8	47	47

×

Coregulation of Androgen receptor activity

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
NRIP1	0	0.045	-9999	-0.56	2	2
SVIL	0.002	0.035	-9999	-0.57	1	1
ZNF318	0.04	0.061	-9999	-10000	0	0
JMJD2C	0.007	0.021	-9999	-0.1	13	13
T-DHT/AR/Ubc9	-0.11	0.18	-9999	-0.39	132	132
CARM1	0.012	0.003	-9999	-10000	0	0
PRDX1	0.015	0.004	-9999	-10000	0	0
PELP1	0.018	0.01	-9999	-10000	0	0
CTNNB1	0.004	0.032	-9999	-0.57	1	1
AKT1	0.021	0.017	-9999	-10000	0	0
PTK2B	0.006	0.03	-9999	-0.57	1	1
MED1	0.02	0.042	-9999	-0.82	1	1
MAK	0.029	0.11	-9999	-0.68	8	8
response to oxidative stress	0.002	0.004	-9999	-10000	0	0
HIP1	0.002	0.035	-9999	-0.57	1	1
GSN	0.002	0.026	-9999	-10000	0	0
NCOA2	-0.032	0.15	-9999	-0.57	38	38
NCOA6	0.002	0.043	-9999	-0.82	1	1
DNA-PK	0.031	0.066	-9999	-10000	0	0
NCOA4	0.011	0.026	-9999	-0.57	1	1
PIAS3	0.005	0.019	-9999	-10000	0	0
cell proliferation	-0.012	0.1	-9999	-0.62	8	8
XRCC5	0.02	0.013	-9999	-10000	0	0
UBE3A	-0.003	0.038	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.13	0.2	-9999	-0.46	96	96
FHL2	-0.017	0.11	-9999	-0.94	2	2
RANBP9	0.004	0.023	-9999	-10000	0	0
JMJD1A	-0.058	0.075	-9999	-0.13	242	242
CDK6	0.001	0.1	-9999	-0.76	9	9
TGFB1I1	-0.022	0.14	-9999	-0.82	15	15
T-DHT/AR/CyclinD1	-0.13	0.19	-9999	-0.45	100	100
XRCC6	0.02	0.013	-9999	-10000	0	0
T-DHT/AR	-0.14	0.2	-9999	-0.5	81	81
CTDSP1	0.011	0.005	-9999	-10000	0	0
CTDSP2	0.032	0.041	-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	230	230
SRF	0.03	0.022	-9999	-10000	0	0
NKX3-1	-0.14	0.15	-9999	-0.79	8	8
KLK3	-0.22	0.54	-9999	-1.4	88	88
TMF1	0.011	0.005	-9999	-10000	0	0
HNRNPA1	0.025	0.025	-9999	-10000	0	0
AOF2	-0.012	0.027	-9999	-0.07	84	84
APPL1	0.041	0.037	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.1	0.18	-9999	-0.43	80	80
AR	-0.17	0.26	-9999	-0.6	132	132
UBA3	0.011	0.005	-9999	-10000	0	0
PATZ1	0.025	0.025	-9999	-10000	0	0
PAWR	0.011	0.005	-9999	-10000	0	0
PRKDC	0.02	0.013	-9999	-10000	0	0
PA2G4	0.026	0.027	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.095	0.16	-9999	-0.36	121	121
RPS6KA3	0	0.045	-9999	-0.57	2	2
T-DHT/AR/ARA70	-0.12	0.18	-9999	-0.39	133	133
LATS2	0.024	0.022	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.089	0.17	-9999	-0.4	79	79
Cyclin D3/CDK11 p58	0.003	0.007	-9999	-10000	0	0
VAV3	-0.035	0.15	-9999	-0.57	35	35
KLK2	-0.072	0.13	-9999	-0.76	13	13
CASP8	0.017	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.43	97	97
TMPRSS2	-0.5	0.5	-9999	-1	236	236
CCND1	-0.008	0.12	-9999	-0.77	12	12
PIAS1	-0.003	0.038	-9999	-10000	0	0
mol:T-DHT	-0.023	0.034	-9999	-0.067	145	145
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.012	0.057	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.12	0.19	-9999	-0.43	106	106
CMTM2	-0.01	0.14	-9999	-0.82	15	15
SNURF	-0.015	0.12	-9999	-0.57	23	23
ZMIZ1	-0.006	0.042	-9999	-0.68	1	1
CCND3	0.015	0.002	-9999	-10000	0	0
TGIF1	0.023	0.046	-9999	-0.82	1	1
FKBP4	0.004	0.023	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0.016	-9999	-0.35	1	1
ADCY5	-0.072	0.17	-9999	-0.36	121	121
ADCY6	0.012	0.059	-9999	-0.35	13	13
ADCY7	0.021	0.016	-9999	-0.35	1	1
ADCY1	-0.005	0.12	-9999	-0.54	23	23
ADCY2	-0.11	0.18	-9999	-0.35	171	171
ADCY3	0.021	0.016	-9999	-0.35	1	1
ADCY8	-0.001	0.088	-9999	-0.54	13	13
PRKCE	0.011	0.019	-9999	-0.42	1	1
ADCY9	0.019	0.028	-9999	-0.35	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.047	0.096	-9999	-0.36	9	9

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.018	0.088	-9999	-0.48	16	16
RGS9BP	-0.001	0.089	-9999	-0.57	12	12
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.001	0.037	-9999	-0.82	1	1
mol:Na +	-0.089	0.2	-9999	-0.55	80	80
mol:ADP	-0.051	0.2	-9999	-0.64	50	50
GNAT2	0.012	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.019	0.09	-9999	-0.54	9	9
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.069	0.25	-9999	-0.82	49	49
CNGB3	-0.12	0.3	-9999	-0.82	79	79
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.17	0.29	-9999	-0.56	161	161
Cone PDE6	-0.017	0.078	-9999	-0.47	9	9
Cone Metarhodopsin II	-0.052	0.16	-9999	-0.52	50	50
Na + (4 Units)	-0.18	0.28	-9999	-0.56	161	161
GNAT2/GDP	-0.016	0.077	-9999	-0.47	9	9
GNB5	0.014	0	-9999	-10000	0	0
mol:GMP (4 units)	0.01	0.006	-9999	-10000	0	0
Cone Transducin	-0.019	0.092	-9999	-0.5	16	16
SLC24A2	-0.16	0.33	-9999	-0.82	101	101
GNB3/GNGT2	-0.023	0.12	-9999	-0.58	20	20
GNB3	-0.014	0.15	-9999	-0.79	17	17
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.007	0.038	-9999	-0.82	1	1
ARR3	0.002	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.089	0.2	-9999	-0.56	80	80
mol:Pi	-0.019	0.09	-9999	-0.54	9	9
Cone CNG Channel	-0.074	0.17	-9999	-0.46	80	80
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.16	0.33	-9999	-0.82	101	101
RGS9	-0.004	0.12	-9999	-0.77	11	11
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	0.01	0.052	-9999	-0.65	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.005	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.017	-10000	0	-10000	0	0
AES	0.003	0.015	-10000	0	-10000	0	0
FBXW11	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.008	0.068	-10000	0	-0.56	7	7
SMAD4	0.013	0.026	-10000	0	-0.57	1	1
DKK2	-0.009	0.13	-10000	0	-0.69	16	16
TLE1	0.003	0.015	-10000	0	-10000	0	0
MACF1	0.014	0.001	-10000	0	-10000	0	0
CTNNB1	0.032	0.11	-10000	0	-0.42	2	2
WIF1	-0.26	0.3	-10000	0	-0.58	219	219
beta catenin/RanBP3	-0.013	0.088	0.37	10	-10000	0	10
KREMEN2	-0.29	0.4	-10000	0	-0.82	183	183
DKK1	-0.28	0.39	-10000	0	-0.8	183	183
beta catenin/beta TrCP1	0.039	0.11	-10000	0	-10000	0	0
FZD1	0.005	0.087	-10000	0	-0.78	6	6
AXIN2	-0.012	0.21	-10000	0	-1.4	11	11
AXIN1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.082	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.006	0.041	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.051	0.074	-10000	0	-10000	0	0
HNF1A	-0.012	0.11	-10000	0	-0.82	9	9
CTBP1	0.003	0.015	-10000	0	-10000	0	0
MYC	0.014	0.045	-10000	0	-0.53	1	1
RANBP3	0.014	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.21	0.27	-10000	0	-0.55	191	191
NKD1	-0.017	0.15	-10000	0	-0.78	19	19
TCF4	0.003	0.016	-10000	0	-10000	0	0
TCF3	0.003	0.015	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.011	0.072	-10000	0	-0.49	10	10
Ran/GTP	0.001	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.013	0.09	0.48	11	-10000	0	11
LEF1	-0.005	0.078	-10000	0	-0.75	5	5
DVL1	0.067	0.05	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.091	0.074	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.39	0.36	-10000	0	-0.66	289	289
LRP6	0.013	0.026	-10000	0	-0.57	1	1
CSNK1A1	0.003	0.017	-10000	0	-10000	0	0
NLK	0.014	0.003	-10000	0	-10000	0	0
CCND1	-0.003	0.15	-10000	0	-0.87	12	12
WNT1	0.002	0.083	-10000	0	-0.82	5	5
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	0.049	0.067	0.36	19	-10000	0	19
APC	0.03	0.074	-10000	0	-0.46	10	10
WNT1/LRP6/FZD1	0.11	0.12	0.24	218	-10000	0	218
CREBBP	0.003	0.015	-10000	0	-10000	0	0

×

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	0.037	-10000	0	-0.82	1	1
RAS family/GTP/Tiam1	-0.067	0.12	-10000	0	-0.48	5	5
NT3 (dimer)/TRKC	-0.22	0.26	-10000	0	-0.49	221	221
NT3 (dimer)/TRKB	-0.22	0.26	-10000	0	-0.66	96	96
SHC/Grb2/SOS1/GAB1/PI3K	0.039	0.021	-10000	0	-10000	0	0
RAPGEF1	0.014	0	-10000	0	-10000	0	0
BDNF	-0.036	0.18	-10000	0	-0.68	36	36
PIK3CA	0.014	0	-10000	0	-10000	0	0
DYNLT1	0.014	0	-10000	0	-10000	0	0
NTRK1	-0.058	0.23	-10000	0	-0.82	43	43
NTRK2	-0.16	0.28	-10000	0	-0.61	138	138
NTRK3	-0.14	0.25	-10000	0	-0.57	127	127
NT-4/5 (dimer)/TRKB	-0.13	0.21	-10000	0	-0.6	45	45
neuron apoptosis	0.12	0.13	0.41	52	-10000	0	52
SHC 2-3/Grb2	-0.12	0.14	-10000	0	-0.44	52	52
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.11	0.14	0.21	1	-0.4	60	61
SHC3	-0.12	0.14	-10000	0	-0.44	54	54
STAT3 (dimer)	0.014	0.053	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.17	0.23	-10000	0	-0.62	63	63
RIN/GDP	-0.047	0.099	-10000	0	-0.28	5	5
GIPC1	0.014	0	-10000	0	-10000	0	0
KRAS	0.01	0.053	-10000	0	-0.82	2	2
DNAJA3	-0.079	0.12	0.25	2	-0.5	6	8
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.014	0.12	-10000	0	-0.74	12	12
MAGED1	0.008	0.064	-10000	0	-0.69	4	4
PTPN11	0.014	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.011	0.045	-10000	0	-0.69	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	-0.16	0.26	-10000	0	-0.57	131	131
TRKA/NEDD4-2	-0.054	0.18	-10000	0	-0.63	43	43
ELMO1	0.013	0.026	-10000	0	-0.57	1	1
RhoG/GTP/ELMO1/DOCK1	-0.002	0.027	-10000	0	-0.35	3	3
NGF	-0.14	0.32	-10000	0	-0.8	91	91
HRAS	0.012	0.037	-10000	0	-0.82	1	1
DOCK1	0.011	0.037	-10000	0	-0.57	2	2
GAB2	0.01	0.045	-10000	0	-0.57	3	3
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.014	0	-10000	0	-10000	0	0
FRS2	0.007	0.074	-10000	0	-0.82	4	4
DNM1	-0.048	0.22	-10000	0	-0.82	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.078	0.12	0.24	2	-0.48	7	9
mol:GDP	-0.07	0.14	-10000	0	-0.41	13	13
NGF (dimer)	-0.14	0.31	-10000	0	-0.8	91	91
RhoG/GDP	-0.001	0.019	-10000	0	-0.42	1	1
RIT1/GDP	-0.041	0.1	-10000	0	-0.28	2	2
TIAM1	0.007	0.063	-10000	0	-0.57	6	6
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
BDNF (dimer)/TRKB	-0.13	0.2	-10000	0	-0.59	44	44
KIDINS220/CRKL/C3G	-0.001	0.028	-10000	0	-0.63	1	1
SHC/RasGAP	-0.002	0.026	-10000	0	-0.41	2	2
FRS2 family/SHP2	-0.004	0.048	-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)	-0.16	0.26	-10000	0	-0.56	148	148
RAP1/GDP	-0.054	0.066	-10000	0	-0.36	1	1
KIDINS220/CRKL	0.012	0.037	-10000	0	-0.82	1	1
BDNF (dimer)	-0.036	0.18	-10000	0	-0.68	36	36
ubiquitin-dependent protein catabolic process	-0.14	0.25	-10000	0	-0.56	121	121
Schwann cell development	-0.048	0.036	-10000	0	-10000	0	0
EHD4	0.014	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.004	0.044	-10000	0	-0.49	4	4
FRS2 family/SHP2/CRK family/C3G/GAB2	0.04	0.031	-10000	0	-10000	0	0
RAP1B	0.012	0.037	-10000	0	-0.82	1	1
RAP1A	0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.25	0.26	-10000	0	-0.61	141	141
ABL1	0.014	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.045	0.07	-10000	0	-0.56	1	1
STAT3	0.014	0.053	-10000	0	-10000	0	0
axon guidance	-0.24	0.25	-10000	0	-0.57	141	141
MAPK3	-0.11	0.25	-10000	0	-0.52	131	131
MAPK1	-0.11	0.25	-10000	0	-0.52	131	131
CDC42/GDP	-0.041	0.1	-10000	0	-0.28	5	5
NTF3	-0.16	0.26	-10000	0	-0.57	148	148
NTF4	0.011	0.045	-10000	0	-0.69	2	2
NGF (dimer)/TRKA/FAIM	-0.14	0.25	-10000	0	-0.56	121	121
PI3K	-0.002	0.031	-10000	0	-0.41	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	-10000	0	-0.57	100	100
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.19	0.26	-10000	0	-0.68	71	71
RGS19	0.014	0	-10000	0	-10000	0	0
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.087	-10000	0	-10000	0	0
Rac1/GDP	-0.041	0.1	-10000	0	-0.28	1	1
NGF (dimer)/TRKA/GRIT	-0.14	0.25	-10000	0	-0.56	129	129
neuron projection morphogenesis	-0.042	0.13	-10000	0	-0.51	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.14	0.25	-10000	0	-0.56	121	121
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.023	0.16	-10000	0	-0.71	25	25
NGF (dimer)/TRKA/GIPC/GAIP	-0.061	0.16	-10000	0	-0.55	14	14
RAS family/GTP/PI3K	0.03	0.031	-10000	0	-0.26	2	2
FRS2 family/SHP2/GRB2/SOS1	-0.004	0.041	-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	0.013	0.026	-10000	0	-0.57	1	1
MAPKKK cascade	-0.084	0.14	-10000	0	-0.48	19	19
RASA1	0.011	0.037	-10000	0	-0.57	2	2
TRKA/c-Abl	-0.054	0.18	-10000	0	-0.63	43	43
SQSTM1	0.014	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.12	0.18	-10000	0	-0.54	44	44
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.12	0.21	-10000	0	-0.48	121	121
MATK	-0.006	0.12	-10000	0	-0.8	12	12
NEDD4L	0.014	0	-10000	0	-10000	0	0
RAS family/GDP	-0.052	0.063	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.086	0.14	0.26	2	-0.37	30	32
Rac1/GTP	-0.12	0.13	-10000	0	-0.36	75	75
FRS2 family/SHP2/CRK family	-0.005	0.046	-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	-0.014	0.079	-10000	0	-0.51	1	1
epithelial cell differentiation	-0.075	0.12	-10000	0	-0.56	3	3
ITCH	0.027	0.019	-10000	0	-10000	0	0
WWP1	-0.009	0.071	-10000	0	-10000	0	0
FYN	0.012	0.037	-10000	0	-0.82	1	1
EGFR	-0.017	0.15	-10000	0	-0.76	20	20
PRL	-0.004	0.082	-10000	0	-0.82	5	5
neuron projection morphogenesis	-0.031	0.17	-10000	0	-10000	0	0
PTPRZ1	-0.011	0.12	-10000	0	-0.57	21	21
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.086	0.16	-10000	0	-0.51	27	27
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.083	0.2	-10000	0	-0.53	76	76
ADAM17	0.025	0.042	-10000	0	-0.56	2	2
ErbB4/ErbB4	-0.023	0.092	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.037	0.098	-10000	0	-0.47	10	10
NCOR1	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.072	0.19	-10000	0	-0.5	77	77
GRIN2B	-0.07	0.19	-10000	0	-0.53	28	28
ErbB4/ErbB2/betacellulin	-0.097	0.16	-10000	0	-0.62	3	3
STAT1	-0.033	0.19	-10000	0	-0.81	28	28
HBEGF	0.012	0.037	-10000	0	-0.82	1	1
PRLR	-0.12	0.24	-10000	0	-0.57	109	109
E4ICDs/ETO2	-0.014	0.077	-10000	0	-10000	0	0
axon guidance	-0.015	0.087	-10000	0	-0.4	2	2
NEDD4	0.027	0.019	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.097	0.18	-10000	0	-0.43	112	112
CBFA2T3	0.013	0.026	-10000	0	-0.57	1	1
ErbB4/ErbB2/HBEGF	0.004	0.074	-10000	0	-0.51	4	4
MAPK3	-0.041	0.17	-10000	0	-10000	0	0
STAT1 (dimer)	-0.043	0.15	-10000	0	-0.57	27	27
MAPK1	-0.041	0.17	-10000	0	-10000	0	0
JAK2	0.013	0.026	-10000	0	-0.57	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.074	0.19	-10000	0	-0.5	79	79
NRG1	-0.075	0.24	-10000	0	-0.61	83	83
NRG3	-0.01	0.11	-10000	0	-0.62	14	14
NRG2	-0.32	0.28	-10000	0	-0.57	287	287
NRG4	-0.032	0.16	-10000	0	-0.58	38	38
heart development	-0.015	0.087	-10000	0	-0.4	2	2
neural crest cell migration	-0.073	0.19	-10000	0	-0.49	79	79
ERBB2	0.027	0.059	-10000	0	-0.53	5	5
WWOX/E4ICDs	-0.013	0.076	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.074	0.13	-10000	0	-0.52	17	17
apoptosis	0.072	0.11	0.59	10	-10000	0	10
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.21	0.19	-10000	0	-0.46	101	101
ErbB4/ErbB2/epiregulin	-0.082	0.16	-10000	0	-0.61	8	8
ErbB4/ErbB4/betacellulin/betacellulin	-0.12	0.18	-10000	0	-0.46	52	52
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.091	0.13	-10000	0	-0.66	4	4
MDM2	-0.01	0.079	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.092	0.18	-10000	0	-0.5	76	76
STAT5A	-0.006	0.082	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.089	0.21	-10000	0	-0.5	89	89
DLG4	0.011	0.045	-10000	0	-0.69	2	2
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.036	0.053	-10000	0	-10000	0	0
STAT5A (dimer)	-0.079	0.12	-10000	0	-0.62	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.081	-10000	0	-10000	0	0
LRIG1	0	0.089	-10000	0	-0.57	12	12
EREG	-0.15	0.26	-10000	0	-0.58	136	136
BTC	-0.17	0.27	-10000	0	-0.57	157	157
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.016	0.088	-10000	0	-10000	0	0
ERBB4	-0.023	0.092	-10000	0	-10000	0	0
STAT5B	0.014	0	-10000	0	-10000	0	0
YAP1	-0.02	0.058	-10000	0	-0.4	10	10
GRB2	0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.021	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	-0.14	0.23	-10000	0	-0.68	40	40

×

Caspase cascade in apoptosis

Figure S34. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S34. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.043	0.18	-10000	0	-0.55	36	36
ACTA1	-0.14	0.24	-10000	0	-0.62	88	88
NUMA1	-0.043	0.18	-10000	0	-0.55	36	36
SPTAN1	-0.069	0.24	-10000	0	-0.56	83	83
LIMK1	-0.069	0.24	-10000	0	-0.56	83	83
BIRC3	-0.021	0.17	-10000	0	-0.82	21	21
BIRC2	-0.005	0.12	-10000	0	-0.82	11	11
BAX	0.014	0	-10000	0	-10000	0	0
CASP10	-0.1	0.3	-10000	0	-0.73	86	86
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.043	0.18	-10000	0	-0.55	36	36
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.067	0.23	-10000	0	-0.54	83	83
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
GSN	-0.069	0.24	-10000	0	-0.56	83	83
MADD	0.014	0	-10000	0	-10000	0	0
TFAP2A	0.001	0.087	-10000	0	-0.52	6	6
BID	-0.03	0.12	-10000	0	-0.36	35	35
MAP3K1	-0.013	0.076	-10000	0	-0.22	30	30
TRADD	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.004	0.021	-10000	0	-0.4	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.069	0.24	-10000	0	-0.77	34	34
CASP9	0.014	0.001	-10000	0	-10000	0	0
DNA repair	0.008	0.064	-10000	0	-0.2	12	12
neuron apoptosis	0.017	0.027	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.06	0.23	-10000	0	-0.75	34	34
APAF1	0.013	0.026	-10000	0	-0.57	1	1
CASP6	-0.005	0.1	-10000	0	-0.47	3	3
TRAF2	0.002	0.098	-10000	0	-0.82	7	7
ICAD/CAD	-0.06	0.23	-10000	0	-0.76	33	33
CASP7	0.006	0.064	0.29	21	-10000	0	21
KRT18	0.001	0.071	-10000	0	-0.44	10	10
apoptosis	-0.049	0.21	-10000	0	-0.68	33	33
DFFA	-0.069	0.24	-10000	0	-0.56	83	83
DFFB	-0.07	0.24	-10000	0	-0.56	83	83
PARP1	-0.008	0.064	0.2	12	-10000	0	12
actin filament polymerization	0.056	0.22	0.69	35	-10000	0	35
TNF	-0.025	0.17	-10000	0	-0.79	24	24
CYCS	-0.02	0.095	-10000	0	-0.28	33	33
SATB1	-0.009	0.12	-10000	0	-0.5	5	5
SLK	-0.069	0.24	-10000	0	-0.56	83	83
p15 BID/BAX	-0.02	0.11	-10000	0	-0.32	33	33
CASP2	0.033	0.075	-10000	0	-10000	0	0
JNK cascade	0.013	0.076	0.22	31	-10000	0	31
CASP3	-0.081	0.25	-10000	0	-0.58	88	88
LMNB2	0.026	0.062	-10000	0	-0.36	3	3
RIPK1	0.014	0	-10000	0	-10000	0	0
CASP4	0.011	0.037	-10000	0	-0.57	2	2
Mammalian IAPs/DIABLO	-0.031	0.14	-10000	0	-0.6	26	26
negative regulation of DNA binding	0.001	0.086	-10000	0	-0.52	6	6
stress fiber formation	-0.067	0.23	-10000	0	-0.54	83	83
GZMB	-0.13	0.34	-10000	0	-0.8	91	91
CASP1	0.016	0.041	-10000	0	-0.58	2	2
LMNB1	0.026	0.062	-10000	0	-0.38	2	2
APP	0.017	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	-0.053	0.21	-10000	0	-0.64	35	35
LMNA	0.026	0.062	-10000	0	-0.36	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.026	0.079	-10000	0	-0.37	10	10
LRDD	0.012	0.037	-10000	0	-0.82	1	1
SREBF1	-0.069	0.24	-10000	0	-0.56	83	83
APAF-1/Caspase 9	-0.001	0.078	0.45	10	-10000	0	10
nuclear fragmentation during apoptosis	-0.042	0.18	-10000	0	-0.54	36	36
CFL2	-0.058	0.22	-10000	0	-0.72	35	35
GAS2	-0.11	0.25	-10000	0	-0.59	86	86
positive regulation of apoptosis	0.03	0.062	-10000	0	-0.37	2	2
PRF1	-0.05	0.22	-10000	0	-0.8	39	39

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.063	0.19	0.6	52	-10000	0	52
KIRREL	-0.022	0.14	-10000	0	-0.62	24	24
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.064	0.19	-10000	0	-0.6	52	52
PLCG1	0.014	0	-10000	0	-10000	0	0
ARRB2	0.014	0	-10000	0	-10000	0	0
WASL	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.057	0.17	-10000	0	-0.58	41	41
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.009	0.12	-10000	0	-0.6	10	10
FYN	-0.036	0.17	-10000	0	-0.52	42	42
mol:Ca2+	-0.057	0.17	-10000	0	-0.57	41	41
mol:DAG	-0.057	0.17	-10000	0	-0.57	41	41
NPHS2	-0.023	0.13	-10000	0	-0.86	12	12
mol:IP3	-0.057	0.17	-10000	0	-0.57	41	41
regulation of endocytosis	-0.039	0.16	-10000	0	-0.49	42	42
Nephrin/NEPH1/podocin/Cholesterol	-0.058	0.18	-10000	0	-0.58	41	41
establishment of cell polarity	-0.063	0.19	-10000	0	-0.6	52	52
Nephrin/NEPH1/podocin/NCK1-2	-0.052	0.16	-10000	0	-0.53	41	41
Nephrin/NEPH1/beta Arrestin2	-0.026	0.16	-10000	0	-0.5	42	42
NPHS1	-0.049	0.21	-10000	0	-0.84	32	32
Nephrin/NEPH1/podocin	-0.052	0.16	-10000	0	-0.53	42	42
TJP1	0.014	0	-10000	0	-10000	0	0
NCK1	0.014	0	-10000	0	-10000	0	0
NCK2	0.014	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.057	0.17	-10000	0	-0.58	41	41
CD2AP	0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.057	0.17	-10000	0	-0.58	41	41
GRB2	0.014	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.065	0.21	-10000	0	-0.54	70	70
cytoskeleton organization	-0.013	0.16	-10000	0	-0.78	10	10
Nephrin/NEPH1	-0.047	0.14	-10000	0	-0.48	44	44
Nephrin/NEPH1/ZO-1	-0.052	0.16	-10000	0	-0.56	36	36

×

Thromboxane A2 receptor 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
TGM2	-0.049	0.22	-10000	0	-0.82	36	36
GNB1/GNG2	-0.056	0.077	-10000	0	-0.21	34	34
AKT1	-0.003	0.12	-10000	0	-0.26	1	1
EGF	-0.094	0.23	-10000	0	-0.57	91	91
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.011	0.12	-10000	0	-0.5	12	12
mol:Ca2+	-0.03	0.16	-10000	0	-0.32	45	45
LYN	0.011	0.12	-10000	0	-0.51	12	12
RhoA/GTP	-0.033	0.049	-10000	0	-0.16	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.032	0.18	-10000	0	-0.36	45	45
GNG2	0.012	0.037	-10000	0	-0.82	1	1
ARRB2	0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.005	0.086	-10000	0	-0.52	5	5
G beta5/gamma2	-0.073	0.1	-10000	0	-0.29	37	37
PRKCH	-0.037	0.18	-10000	0	-0.38	40	40
DNM1	-0.048	0.22	-10000	0	-0.82	37	37
TXA2/TP beta/beta Arrestin3	-0.025	0.069	-10000	0	-0.26	37	37
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0	0.1	-10000	0	-0.74	9	9
G12 family/GTP	-0.082	0.12	-10000	0	-0.32	49	49
ADRBK1	0.014	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.037	-10000	0	-0.82	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.13	0.36	29	-10000	0	29
mol:NADP	-0.001	0.11	-10000	0	-0.82	9	9
RAB11A	0.014	0	-10000	0	-10000	0	0
PRKG1	-0.021	0.15	-10000	0	-0.65	26	26
mol:IP3	-0.045	0.19	-10000	0	-0.41	45	45
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.073	0.25	-10000	0	-0.56	47	47
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.045	0.18	-10000	0	-0.43	70	70
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.009	0.13	-10000	0	-0.52	13	13
RHOA	0.014	0	-10000	0	-10000	0	0
PTGIR	-0.018	0.16	-10000	0	-0.82	19	19
PRKCB1	-0.045	0.19	-10000	0	-0.38	90	90
GNAQ	0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	-0.001	0.11	-10000	0	-0.82	9	9
TXA2/TXA2-R family	-0.073	0.26	-10000	0	-0.52	91	91
LCK	0.002	0.13	-10000	0	-0.47	17	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.043	0.14	-10000	0	-0.5	36	36
TXA2-R family/G12 family/GDP/G beta/gamma	0.021	0.045	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.042	0.14	-10000	0	-0.49	36	36
MAPK14	-0.009	0.13	-10000	0	-0.25	9	9
TGM2/GTP	-0.059	0.22	-10000	0	-0.48	43	43
MAPK11	-0.009	0.13	-10000	0	-0.28	1	1
ARHGEF1	-0.008	0.099	-10000	0	-0.22	2	2
GNAI2	0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.044	0.2	-10000	0	-0.38	89	89
RAB11/GDP	0.014	0.002	-10000	0	-10000	0	0
ICAM1	-0.029	0.16	-10000	0	-0.34	49	49
cAMP biosynthetic process	-0.045	0.18	-10000	0	-0.39	41	41
Gq family/GTP/EBP50	-0.007	0.096	-10000	0	-0.64	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.012	0.12	-10000	0	-0.5	11	11
GNB5	0.014	0	-10000	0	-10000	0	0
GNB1	0.014	0	-10000	0	-10000	0	0
EGF/EGFR	-0.004	0.12	-10000	0	-0.35	18	18
VCAM1	-0.038	0.18	-10000	0	-0.37	65	65
TP beta/Gq family/GDP/G beta5/gamma2	0.005	0.086	-10000	0	-0.52	5	5
platelet activation	-0.014	0.17	-10000	0	-0.32	32	32
PGI2/IP	-0.024	0.12	-10000	0	-0.64	19	19
PRKACA	0.004	0.085	-10000	0	-0.36	24	24
Gq family/GDP/G beta5/gamma2	0.009	0.076	-10000	0	-0.42	5	5
TXA2/TP beta/beta Arrestin2	-0.03	0.095	-10000	0	-0.36	37	37
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.022	0.17	-10000	0	-0.57	36	36
mol:DAG	-0.053	0.21	-10000	0	-0.42	90	90
EGFR	-0.017	0.15	-10000	0	-0.76	20	20
TXA2/TP alpha	-0.067	0.24	-10000	0	-0.54	41	41
Gq family/GTP	-0.034	0.09	-10000	0	-0.24	77	77
YES1	0.012	0.12	-10000	0	-0.5	11	11
GNAI2/GTP	-0.039	0.12	-10000	0	-0.47	27	27
PGD2/DP	-0.01	0.076	-10000	0	-0.56	9	9
SLC9A3R1	0.009	0.052	-10000	0	-0.57	4	4
FYN	0.011	0.12	-10000	0	-0.52	12	12
mol:NO	-0.001	0.11	-10000	0	-0.82	9	9
GNA15	0.011	0.037	-10000	0	-0.57	2	2
PGK/cGMP	-0.032	0.12	-10000	0	-0.45	35	35
RhoA/GDP	0.014	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.072	0.19	-10000	0	-0.6	39	39
NOS3	-0.001	0.11	-10000	0	-0.82	9	9
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.038	0.18	-10000	0	-0.38	39	39
PRKCB	-0.042	0.19	-10000	0	-0.4	43	43
PRKCE	-0.037	0.18	-10000	0	-0.36	82	82
PRKCD	-0.042	0.19	-10000	0	-0.38	85	85
PRKCG	-0.066	0.22	-10000	0	-0.43	96	96
muscle contraction	-0.062	0.24	-10000	0	-0.48	91	91
PRKCZ	-0.032	0.18	-10000	0	-0.37	35	35
ARR3	0.002	0.005	-10000	0	-10000	0	0
TXA2/TP beta	-0.043	0.14	-10000	0	-0.5	37	37
PRKCQ	-0.042	0.18	-10000	0	-0.4	44	44
MAPKKK cascade	-0.058	0.22	-10000	0	-0.47	52	52
SELE	-0.043	0.18	-10000	0	-0.39	84	84
TP beta/GNAI2/GDP/G beta/gamma	-0.043	0.14	-10000	0	-0.69	11	11
ROCK1	0.014	0	-10000	0	-10000	0	0
GNA14	-0.075	0.21	-10000	0	-0.57	76	76
chemotaxis	-0.087	0.29	-10000	0	-0.6	96	96
GNA12	0.01	0.053	-10000	0	-0.82	2	2
GNA13	0.014	0	-10000	0	-10000	0	0
GNA11	0.009	0.052	-10000	0	-0.57	4	4
Rac1/GTP	0.006	0.006	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.13	0.24	-10000	0	-0.55	121	121
cell-cell adhesion	0.11	0.17	0.64	7	-10000	0	7
Ephrin B/EPHB2/RasGAP	-0.12	0.2	-10000	0	-0.48	106	106
ITSN1	0.014	0	-10000	0	-10000	0	0
PIK3CA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.01	0.057	-10000	0	-0.35	14	14
Ephrin B1/EPHB1	-0.027	0.11	-10000	0	-0.48	28	28
HRAS/GDP	-0.054	0.11	-10000	0	-0.56	5	5
Ephrin B/EPHB1/GRB7	-0.046	0.13	-10000	0	-0.49	24	24
Endophilin/SYNJ1	-0.081	0.2	-10000	0	-0.44	106	106
KRAS	0.01	0.053	-10000	0	-0.82	2	2
Ephrin B/EPHB1/Src	-0.041	0.12	-10000	0	-0.49	20	20
endothelial cell migration	-0.003	0.028	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
GRB7	0.005	0.083	-10000	0	-0.74	6	6
PAK1	-0.1	0.22	-10000	0	-0.64	17	17
HRAS	0.012	0.037	-10000	0	-0.82	1	1
RRAS	-0.082	0.21	-10000	0	-0.45	106	106
DNM1	-0.048	0.22	-10000	0	-0.82	37	37
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.003	0.13	-10000	0	-0.47	20	20
lamellipodium assembly	-0.11	0.17	-10000	0	-0.64	7	7
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.011	0.091	-10000	0	-0.46	3	3
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
EPHB2	-0.16	0.34	-10000	0	-0.82	107	107
EPHB3	-0.003	0.096	-10000	0	-0.57	14	14
EPHB1	-0.028	0.17	-10000	0	-0.73	28	28
EPHB4	0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.051	0.11	-10000	0	-0.57	4	4
Ephrin B/EPHB2	-0.12	0.2	-10000	0	-0.48	106	106
Ephrin B/EPHB3	-0.027	0.086	-10000	0	-0.52	2	2
JNK cascade	-0.088	0.22	-10000	0	-0.46	123	123
Ephrin B/EPHB1	-0.042	0.12	-10000	0	-0.5	20	20
RAP1/GDP	-0.042	0.092	-10000	0	-0.55	2	2
EFNB2	0.011	0.037	-10000	0	-0.57	2	2
EFNB3	-0.024	0.14	-10000	0	-0.57	32	32
EFNB1	0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.13	0.22	-10000	0	-0.51	123	123
RAP1B	0.012	0.037	-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	7	7
Rap1/GTP	-0.11	0.17	-10000	0	-0.74	5	5
axon guidance	-0.13	0.24	-10000	0	-0.54	121	121
MAPK3	0.027	0.083	-10000	0	-0.4	3	3
MAPK1	0.027	0.083	-10000	0	-0.42	1	1
Rac1/GDP	-0.01	0.12	-10000	0	-0.51	4	4
actin cytoskeleton reorganization	-0.089	0.14	-10000	0	-0.54	6	6
CDC42/GDP	-0.01	0.12	-10000	0	-0.51	4	4
PI3K	-0.003	0.028	-10000	0	-10000	0	0
EFNA5	-0.012	0.12	-10000	0	-0.57	22	22
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.35	2	2
Ephrin B/EPHB2/Intersectin/N-WASP	-0.043	0.14	-10000	0	-0.55	4	4
CDC42	0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.11	0.17	-10000	0	-0.71	6	6
PTK2	0.027	0.045	-10000	0	-10000	0	0
MAP4K4	-0.089	0.22	-10000	0	-0.46	123	123
SRC	0.014	0	-10000	0	-10000	0	0
KALRN	-0.038	0.16	-10000	0	-0.57	44	44
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.049	0.17	-10000	0	-0.54	6	6
MAP2K1	0.019	0.086	-10000	0	-0.43	3	3
WASL	0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.13	0.22	-10000	0	-0.5	123	123
cell migration	0.023	0.099	-10000	0	-0.49	3	3
NRAS	0.014	0	-10000	0	-10000	0	0
SYNJ1	-0.082	0.21	-10000	0	-0.45	106	106
PXN	0.014	0	-10000	0	-10000	0	0
TF	-0.26	0.24	-10000	0	-0.66	97	97
HRAS/GTP	-0.12	0.19	-10000	0	-0.72	8	8
Ephrin B1/EPHB1-2	-0.13	0.22	-10000	0	-0.51	123	123
cell adhesion mediated by integrin	0.015	0.079	0.44	2	-10000	0	2
RAC1	0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.13	0.2	-10000	0	-0.79	7	7
RAC1-CDC42/GTP	-0.12	0.17	-10000	0	-0.68	8	8
RASA1	0.011	0.037	-10000	0	-0.57	2	2
RAC1-CDC42/GDP	-0.042	0.091	-10000	0	-0.55	2	2
ruffle organization	-0.065	0.2	-10000	0	-0.74	5	5
NCK1	0.014	0	-10000	0	-10000	0	0
receptor internalization	-0.1	0.25	-10000	0	-0.64	40	40
Ephrin B/EPHB2/KALRN	-0.14	0.21	-10000	0	-0.49	114	114
ROCK1	0.018	0.055	-10000	0	-10000	0	0
RAS family/GDP	-0.087	0.13	-10000	0	-0.55	6	6
Rac1/GTP	-0.12	0.18	-10000	0	-0.71	7	7
Ephrin B/EPHB1/Src/Paxillin	0.005	0.098	-10000	0	-0.51	3	3

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.03	0.15	-9999	-0.43	27	27
IKBKB	-0.008	0.079	-9999	-0.27	7	7
AKT1	-0.029	0.12	-9999	-0.29	41	41
IKBKG	-0.007	0.082	-9999	-0.29	7	7
CALM1	-0.045	0.12	-9999	-0.41	29	29
PIK3CA	0.014	0	-9999	-10000	0	0
MAP3K1	-0.059	0.21	-9999	-0.63	31	31
MAP3K7	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.055	0.12	-9999	-0.43	31	31
DOK1	0.012	0.037	-9999	-0.82	1	1
AP-1	-0.021	0.097	-9999	-0.27	10	10
LYN	0.012	0.037	-9999	-0.82	1	1
BLNK	-0.042	0.17	-9999	-0.57	48	48
SHC1	0.014	0	-9999	-10000	0	0
BCR complex	-0.14	0.28	-9999	-0.63	109	109
CD22	-0.13	0.27	-9999	-0.81	55	55
CAMK2G	-0.034	0.11	-9999	-0.38	29	29
CSNK2A1	0.014	0	-9999	-10000	0	0
INPP5D	0.01	0.045	-9999	-0.57	3	3
SHC/GRB2/SOS1	-0.11	0.19	-9999	-0.63	30	30
GO:0007205	-0.056	0.13	-9999	-0.44	31	31
SYK	0.01	0.045	-9999	-0.57	3	3
ELK1	-0.046	0.12	-9999	-0.42	30	30
NFATC1	-0.068	0.19	-9999	-0.48	71	71
B-cell antigen/BCR complex	-0.14	0.28	-9999	-0.63	109	109
PAG1/CSK	-0.003	0.04	-9999	-0.63	2	2
NFKBIB	0.008	0.03	-9999	-10000	0	0
HRAS	-0.049	0.13	-9999	-0.44	29	29
NFKBIA	0.008	0.03	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.014	0.025	-9999	-10000	0	0
RasGAP/Csk	-0.11	0.22	-9999	-0.55	79	79
mol:GDP	-0.054	0.12	-9999	-0.42	29	29
PTEN	0.014	0	-9999	-10000	0	0
CD79B	-0.02	0.15	-9999	-0.71	23	23
NF-kappa-B/RelA/I kappa B alpha	0.015	0.024	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.094	0.23	-9999	-0.55	82	82
PIK3R1	0.01	0.045	-9999	-0.57	3	3
mol:IP3	-0.057	0.13	-9999	-0.44	31	31
CSK	0.014	0	-9999	-10000	0	0
FOS	-0.071	0.15	-9999	-0.43	49	49
CHUK	-0.007	0.082	-9999	-0.29	7	7
IBTK	0.014	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.07	0.13	-9999	-0.57	15	15
PTPN6	-0.12	0.25	-9999	-0.75	55	55
RELA	0.014	0	-9999	-10000	0	0
BCL2A1	0.007	0.04	-9999	-0.13	32	32
VAV2	-0.15	0.27	-9999	-0.74	74	74
ubiquitin-dependent protein catabolic process	0.013	0.029	-9999	-10000	0	0
BTK	-0.003	0.035	-9999	-10000	0	0
CD19	-0.15	0.3	-9999	-0.77	83	83
MAP4K1	-0.008	0.13	-9999	-0.76	14	14
CD72	-0.095	0.28	-9999	-0.82	65	65
PAG1	0.01	0.053	-9999	-0.82	2	2
MAPK14	-0.04	0.18	-9999	-0.53	28	28
SH3BP5	0.01	0.045	-9999	-0.57	3	3
PIK3AP1	-0.061	0.16	-9999	-0.47	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.09	0.2	-9999	-0.58	45	45
RAF1	-0.038	0.13	-9999	-0.41	29	29
RasGAP/p62DOK/SHIP	-0.1	0.21	-9999	-0.77	23	23
CD79A	-0.14	0.31	-9999	-0.74	104	104
re-entry into mitotic cell cycle	-0.022	0.097	-9999	-0.27	12	12
RASA1	0.011	0.037	-9999	-0.57	2	2
MAPK3	-0.017	0.11	-9999	-0.42	3	3
MAPK1	-0.017	0.11	-9999	-0.42	3	3
CD72/SHP1	-0.12	0.31	-9999	-0.88	52	52
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	-0.043	0.18	-9999	-0.53	29	29
actin cytoskeleton organization	-0.092	0.24	-9999	-0.61	74	74
NF-kappa-B/RelA	0.034	0.047	-9999	-10000	0	0
Calcineurin	-0.047	0.088	-9999	-0.44	3	3
PI3K	-0.13	0.22	-9999	-0.62	70	70
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.069	0.13	-9999	-0.47	33	33
SOS1	0.014	0	-9999	-10000	0	0
Bam32/HPK1	-0.063	0.23	-9999	-0.76	36	36
DAPP1	-0.092	0.21	-9999	-0.77	32	32
cytokine secretion	-0.062	0.18	-9999	-0.44	71	71
mol:DAG	-0.057	0.13	-9999	-0.44	31	31
PLCG2	0.013	0.026	-9999	-0.57	1	1
MAP2K1	-0.028	0.12	-9999	-0.39	18	18
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.25	-9999	-0.64	79	79
mol:PI-3-4-5-P3	-0.09	0.15	-9999	-0.41	69	69
ETS1	-0.027	0.11	-9999	-0.39	11	11
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.23	-9999	-0.55	89	89
B-cell antigen/BCR complex/LYN	-0.094	0.2	-9999	-0.73	28	28
MALT1	0.014	0	-9999	-10000	0	0
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	-0.1	0.26	-9999	-0.66	74	74
B-cell antigen/BCR complex/LYN/SYK	-0.13	0.27	-9999	-0.88	45	45
CARD11	-0.073	0.17	-9999	-0.5	53	53
FCGR2B	0.006	0.068	-9999	-0.57	7	7
PPP3CA	0.014	0	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
IKK complex	0.007	0.039	-9999	-10000	0	0
PTPRC	-0.004	0.11	-9999	-0.68	13	13
PDPK1	-0.029	0.12	-9999	-0.29	41	41
PPP3CB	0.014	0	-9999	-10000	0	0
PPP3CC	0.014	0	-9999	-10000	0	0
POU2F2	0.008	0.04	-9999	-0.14	30	30

×

PDGFR-beta signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.063	0.13	-9999	-0.68	1	1
PDGFB-D/PDGFRB/SLAP	-0.11	0.24	-9999	-0.62	92	92
PDGFB-D/PDGFRB/APS/CBL	-0.097	0.2	-9999	-0.53	91	91
AKT1	-0.013	0.16	-9999	-0.6	3	3
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.032	0.15	-9999	-0.71	1	1
PIK3CA	0.014	0	-9999	-10000	0	0
FGR	-0.071	0.16	-9999	-0.41	22	22
mol:Ca2+	-0.03	0.14	-9999	-0.4	1	1
MYC	0.004	0.11	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.074	0.17	-9999	-0.43	91	91
LRP1/PDGFRB/PDGFB	-0.11	0.22	-9999	-0.56	96	96
GRB10	0.012	0.037	-9999	-0.82	1	1
PTPN11	0.014	0	-9999	-10000	0	0
GO:0007205	-0.031	0.14	-9999	-0.4	1	1
PTEN	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
GRB7	0.005	0.083	-9999	-0.74	6	6
PDGFB-D/PDGFRB/SHP2	-0.11	0.24	-9999	-0.62	89	89
PDGFB-D/PDGFRB/GRB10	-0.11	0.24	-9999	-0.62	90	90
cell cycle arrest	-0.11	0.24	-9999	-0.62	92	92
HRAS	0.012	0.037	-9999	-0.82	1	1
HIF1A	-0.002	0.15	-9999	-0.51	3	3
GAB1	-0.031	0.14	-9999	-0.46	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.025	0.14	-9999	-0.47	1	1
PDGFB-D/PDGFRB	-0.092	0.21	-9999	-0.54	90	90
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.11	0.24	-9999	-0.62	89	89
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.065	0.13	-9999	-0.69	1	1
positive regulation of MAPKKK cascade	-0.11	0.24	-9999	-0.62	89	89
PIK3R1	0.01	0.045	-9999	-0.57	3	3
mol:IP3	-0.031	0.14	-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	-0.11	0.25	-9999	-0.62	93	93
SHB	0.011	0.037	-9999	-0.57	2	2
BLK	-0.12	0.19	-9999	-0.45	99	99
PTPN2	0.012	0.037	-9999	-0.82	1	1
PDGFB-D/PDGFRB/SNX15	-0.11	0.24	-9999	-0.62	89	89
BCAR1	0.014	0	-9999	-10000	0	0
VAV2	-0.027	0.14	-9999	-0.43	5	5
CBL	0.014	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.11	0.24	-9999	-0.62	89	89
LCK	-0.078	0.16	-9999	-0.47	1	1
PDGFRB	-0.13	0.32	-9999	-0.82	89	89
ACP1	0.014	0	-9999	-10000	0	0
HCK	-0.072	0.16	-9999	-0.49	2	2
ABL1	-0.038	0.15	-9999	-0.41	13	13
PDGFB-D/PDGFRB/CBL	-0.03	0.14	-9999	-0.42	1	1
PTPN1	0.013	0.003	-9999	-10000	0	0
SNX15	0.014	0	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
STAT1	-0.033	0.19	-9999	-0.81	28	28
cell proliferation	0.006	0.1	-9999	-10000	0	0
SLA	0.009	0.064	-9999	-0.82	3	3
actin cytoskeleton reorganization	-0.029	0.18	-9999	-10000	0	0
SRC	-0.07	0.16	-9999	-0.41	12	12
PI3K	-0.073	0.15	-9999	-0.68	3	3
PDGFB-D/PDGFRB/GRB7/SHC	-0.1	0.21	-9999	-0.54	92	92
SH2B2	0.01	0.053	-9999	-0.82	2	2
PLCgamma1/SPHK1	-0.033	0.15	-9999	-0.74	1	1
LYN	-0.07	0.16	-9999	-0.46	1	1
LRP1	0.013	0.026	-9999	-0.57	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	-0.075	0.16	-9999	-10000	0	0
SPHK1	-0.007	0.13	-9999	-0.82	12	12
EDG1	-0.001	0.004	-9999	-10000	0	0
mol:DAG	-0.031	0.14	-9999	-0.4	1	1
PLCG1	-0.032	0.14	-9999	-0.41	1	1
NHERF/PDGFRB	-0.1	0.21	-9999	-0.54	90	90
YES1	-0.07	0.16	-9999	-0.42	13	13
cell migration	-0.099	0.21	-9999	-0.54	90	90
SHC/Grb2/SOS1	-0.075	0.16	-9999	-10000	0	0
SLC9A3R2	0.01	0.053	-9999	-0.82	2	2
SLC9A3R1	0.009	0.052	-9999	-0.57	4	4
NHERF1-2/PDGFRB/PTEN	-0.09	0.19	-9999	-0.49	90	90
FYN	-0.07	0.16	-9999	-0.43	13	13
DOK1	-0.058	0.2	-9999	-0.48	91	91
HRAS/GTP	-0.001	0.029	-9999	-0.64	1	1
PDGFB	-0.006	0.13	-9999	-0.82	12	12
RAC1	-0.011	0.14	-9999	-10000	0	0
PRKCD	-0.057	0.2	-9999	-0.48	90	90
FER	-0.058	0.2	-9999	-0.48	90	90
MAPKKK cascade	-0.074	0.16	-9999	-10000	0	0
RASA1	-0.058	0.2	-9999	-0.48	90	90
NCK1	0.014	0	-9999	-10000	0	0
NCK2	0.014	0	-9999	-10000	0	0
p62DOK/Csk	-0.074	0.17	-9999	-0.44	91	91
PDGFB-D/PDGFRB/SHB	-0.11	0.24	-9999	-0.61	91	91
chemotaxis	-0.037	0.15	-9999	-0.4	13	13
STAT1-3-5/STAT1-3-5	-0.096	0.18	-9999	-0.84	6	6
Bovine Papilomavirus E5/PDGFRB	-0.1	0.24	-9999	-0.63	89	89
PTPRJ	0.014	0	-9999	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0.026	-9999	-0.57	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.025	0.073	-9999	-0.69	1	1
IRAK/TOLLIP	0.033	0.004	-9999	-10000	0	0
IKBKB	0.014	0	-9999	-10000	0	0
IKBKG	0.014	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.24	0.29	-9999	-0.57	210	210
IL1A	-0.2	0.36	-9999	-0.8	131	131
IL1B	-0.044	0.2	-9999	-0.61	54	54
IRAK/TRAF6/p62/Atypical PKCs	0	0.011	-9999	-10000	0	0
IL1R2	-0.098	0.24	-9999	-0.58	93	93
IL1R1	0.013	0.026	-9999	-0.57	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.022	0.076	-9999	-0.72	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	0.072	0.005	-9999	-10000	0	0
JUN	0.033	0.071	-9999	-0.47	2	2
MAP3K7	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.05	0.14	-9999	-0.82	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.13	0.22	-9999	-0.5	126	126
PIK3R1	0.01	0.045	-9999	-0.57	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.12	0.2	-9999	-0.46	127	127
IL1 beta fragment/IL1R1/IL1RAP	-0.023	0.17	-9999	-0.5	51	51
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.026	0.075	-9999	-0.52	2	2
IRAK1	0.028	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.11	0.18	-9999	-0.41	129	129
IRAK4	0.013	0.026	-9999	-0.57	1	1
PRKCI	0.014	0	-9999	-10000	0	0
TRAF6	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.031	-9999	-0.41	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.012	0.092	-9999	-0.81	1	1
CHUK	0.014	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.023	0.17	-9999	-0.5	51	51
IL1 beta/IL1R2	-0.12	0.21	-9999	-0.56	60	60
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.044	0.12	-9999	-0.73	1	1
IRAK3	0.003	0.091	-9999	-0.75	7	7
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.049	0.14	-9999	-0.82	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.041	0.14	-9999	-0.7	2	2
IL1 alpha/IL1R1/IL1RAP	-0.14	0.24	-9999	-0.55	126	126
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	0.041	0.003	-9999	-10000	0	0
IL1RAP	0.01	0.052	-9999	-0.65	3	3
UBE2N	0.014	0	-9999	-10000	0	0
IRAK/TRAF6	-0.039	0.11	-9999	-0.67	1	1
CASP1	0.013	0.026	-9999	-0.57	1	1
IL1RN/IL1R2	-0.18	0.26	-9999	-0.49	181	181
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.051	0.14	-9999	-0.47	51	51
TMEM189-UBE2V1	0.01	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.014	0.11	-9999	-0.67	2	2
PIK3CA	0.014	0	-9999	-10000	0	0
IL1RN	-0.14	0.25	-9999	-0.57	129	129
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.023	0.066	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.082	0.14	-10000	0	-0.5	5	5
regulation of S phase of mitotic cell cycle	-0.043	0.12	-10000	0	-10000	0	0
GNAO1	0.007	0.069	-10000	0	-0.76	4	4
HRAS	0.012	0.037	-10000	0	-0.82	1	1
SHBG/T-DHT	-0.001	0.036	-10000	0	-0.56	2	2
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.039	0.13	-10000	0	-0.52	2	2
T-DHT/AR	-0.11	0.19	-10000	0	-0.42	132	132
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	64	64
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.013	0.026	-10000	0	-0.57	1	1
mol:GDP	-0.12	0.19	-10000	0	-0.43	132	132
cell proliferation	-0.048	0.18	-10000	0	-0.58	19	19
PIK3CA	0.014	0	-10000	0	-10000	0	0
FOS	-0.084	0.29	-10000	0	-0.82	64	64
mol:Ca2+	-0.014	0.021	-10000	0	-0.088	11	11
MAPK3	-0.042	0.16	-10000	0	-0.49	19	19
MAPK1	-0.017	0.091	-10000	0	-0.3	2	2
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
mol:IP3	0	0.002	-10000	0	-0.004	64	64
cAMP biosynthetic process	0.011	0.04	-10000	0	-0.52	2	2
GNG2	0.012	0.037	-10000	0	-0.82	1	1
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	64	64
HRAS/GTP	-0.077	0.12	-10000	0	-0.47	5	5
actin cytoskeleton reorganization	-0.002	0.02	-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	64	64
PI3K	-0.002	0.027	-10000	0	-0.35	3	3
apoptosis	0.041	0.17	0.42	64	-10000	0	64
T-DHT/AR/PELP1	-0.093	0.16	-10000	0	-0.35	132	132
HRAS/GDP	-0.11	0.18	-10000	0	-0.4	133	133
CREB1	-0.045	0.18	-10000	0	-0.45	64	64
RAC1-CDC42/GTP	-0.002	0.021	-10000	0	-10000	0	0
AR	-0.14	0.26	-10000	0	-0.57	132	132
GNB1	0.014	0	-10000	0	-10000	0	0
RAF1	-0.047	0.14	-10000	0	-0.46	5	5
RAC1-CDC42/GDP	-0.1	0.17	-10000	0	-0.4	15	15
T-DHT/AR/PELP1/Src	-0.083	0.14	-10000	0	-0.51	4	4
MAP2K2	-0.039	0.13	-10000	0	-0.52	2	2
T-DHT/AR/PELP1/Src/PI3K	-0.044	0.12	-10000	0	-10000	0	0
GNAZ	-0.017	0.15	-10000	0	-0.74	20	20
SHBG	0.009	0.053	-10000	0	-0.82	2	2
Gi family/GNB1/GNG2/GDP	0.012	0.072	-10000	0	-0.46	2	2
mol:T-DHT	0	0.001	-10000	0	-0.003	45	45
RAC1	0.014	0	-10000	0	-10000	0	0
GNRH1	-0.015	0.13	-10000	0	-0.63	21	21
Gi family/GTP	-0.043	0.081	-10000	0	-0.38	9	9
CDC42	0.014	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.012	0.063	-10000	0	-0.81	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.062	0.19	0.65	26	-10000	0	26
IL27/IL27R/JAK1	-0.11	0.21	-10000	0	-0.82	23	23
TBX21	-0.1	0.26	-10000	0	-0.71	44	44
IL12B	-0.062	0.24	-10000	0	-0.83	43	43
IL12A	-0.008	0.095	-10000	0	-0.48	19	19
IL6ST	-0.062	0.2	-10000	0	-0.58	62	62
IL27RA/JAK1	-0.01	0.11	-10000	0	-0.59	17	17
IL27	-0.031	0.18	-10000	0	-0.84	23	23
TYK2	0.011	0.039	-10000	0	-0.84	1	1
T-helper cell lineage commitment	-0.017	0.12	-10000	0	-0.64	8	8
T-helper 2 cell differentiation	0.062	0.19	0.65	26	-10000	0	26
T cell proliferation during immune response	0.062	0.19	0.65	26	-10000	0	26
MAPKKK cascade	-0.062	0.19	-10000	0	-0.65	26	26
STAT3	0.014	0	-10000	0	-10000	0	0
STAT2	0.014	0	-10000	0	-10000	0	0
STAT1	-0.034	0.19	-10000	0	-0.82	28	28
IL12RB1	-0.064	0.24	-10000	0	-0.81	46	46
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.15	0.32	-10000	0	-0.69	105	105
IL27/IL27R/JAK2/TYK2	-0.063	0.19	-10000	0	-0.67	25	25
positive regulation of T cell mediated cytotoxicity	-0.062	0.19	-10000	0	-0.65	26	26
STAT1 (dimer)	-0.18	0.31	0.52	1	-0.93	46	47
JAK2	0.011	0.027	-10000	0	-0.57	1	1
JAK1	0.013	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.052	0.18	-10000	0	-0.63	25	25
T cell proliferation	-0.081	0.21	-10000	0	-0.65	32	32
IL12/IL12R/TYK2/JAK2	-0.064	0.19	-10000	0	-0.71	17	17
IL17A	-0.019	0.12	-10000	0	-0.64	8	8
mast cell activation	0.062	0.19	0.65	26	-10000	0	26
IFNG	-0.019	0.051	-10000	0	-0.11	109	109
T cell differentiation	-0.007	0.009	-10000	0	-0.024	68	68
STAT3 (dimer)	-0.052	0.18	-10000	0	-0.7	18	18
STAT5A (dimer)	-0.052	0.18	-10000	0	-0.64	24	24
STAT4 (dimer)	-0.063	0.2	-10000	0	-0.67	29	29
STAT4	-0.006	0.12	-10000	0	-0.8	12	12
T cell activation	-0.006	0.02	0.093	17	-10000	0	17
IL27R/JAK2/TYK2	-0.052	0.17	-10000	0	-0.7	14	14
GATA3	0.001	0.15	-10000	0	-0.71	17	17
IL18	-0.005	0.082	-10000	0	-0.42	19	19
positive regulation of mast cell cytokine production	-0.051	0.18	-10000	0	-0.68	18	18
IL27/EBI3	-0.034	0.17	-10000	0	-0.64	34	34
IL27RA	-0.019	0.12	-10000	0	-0.64	17	17
IL6	-0.043	0.19	-10000	0	-0.61	46	46
STAT5A	0.014	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.016	0.067	0.39	1	-10000	0	1
IL1B	-0.056	0.2	-10000	0	-0.62	53	53
EBI3	-0.008	0.12	-10000	0	-0.74	12	12
TNF	-0.018	0.13	-10000	0	-0.61	24	24

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.12	-9999	-0.82	10	10
Syndecan-3/Src/Cortactin	-0.1	0.14	-9999	-0.57	11	11
Syndecan-3/Neurocan	-0.026	0.1	-9999	-0.45	28	28
POMC	-0.081	0.26	-9999	-0.77	60	60
EGFR	-0.017	0.15	-9999	-0.76	20	20
Syndecan-3/EGFR	-0.018	0.086	-9999	-0.45	17	17
AGRP	0.005	0.007	-9999	-10000	0	0
NCSTN	0.014	0	-9999	-10000	0	0
PSENEN	0.01	0.053	-9999	-0.82	2	2
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0	-9999	-10000	0	0
APH1A	0.014	0	-9999	-10000	0	0
NCAN	-0.033	0.18	-9999	-0.82	26	26
long-term memory	-0.011	0.066	-9999	-0.41	13	13
Syndecan-3/IL8	-0.099	0.19	-9999	-0.46	104	104
PSEN1	0.014	0	-9999	-10000	0	0
Src/Cortactin	-0.013	0.088	-9999	-0.63	10	10
FYN	0.012	0.037	-9999	-0.82	1	1
limb bud formation	-0.002	0.024	-9999	-0.37	2	2
MC4R	0.005	0.038	-9999	-0.82	1	1
SRC	0.014	0	-9999	-10000	0	0
PTN	-0.21	0.28	-9999	-0.57	189	189
FGFR/FGF/Syndecan-3	-0.002	0.024	-9999	-0.38	2	2
neuron projection morphogenesis	-0.12	0.16	-9999	-0.49	36	36
Syndecan-3/AgRP	-0.002	0.023	-9999	-0.36	2	2
Syndecan-3/AgRP/MC4R	-0.003	0.029	-9999	-0.44	1	1
Fyn/Cortactin	-0.014	0.092	-9999	-0.63	11	11
SDC3	-0.002	0.025	-9999	-0.38	2	2
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.098	0.19	-9999	-0.46	104	104
IL8	-0.16	0.34	-9999	-0.81	106	106
Syndecan-3/Fyn/Cortactin	-0.011	0.068	-9999	-0.42	13	13
Syndecan-3/CASK	-0.002	0.023	-9999	-0.36	2	2
alpha-MSH/MC4R	-0.072	0.2	-9999	-0.6	60	60
Gamma Secretase	-0.002	0.029	-9999	-0.46	2	2

×

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	0.006	0.038	-10000	0	-0.56	2	2
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.032	0.16	-10000	0	-0.55	17	17
AKT1	0.001	0.033	-10000	0	-10000	0	0
GSC	-0.014	0.19	-10000	0	-0.71	30	30
NKX2-5	-0.16	0.32	-10000	0	-0.72	119	119
muscle cell differentiation	0.12	0.2	0.62	46	-10000	0	46
SMAD2-3/SMAD4/SP1	-0.039	0.099	-10000	0	-10000	0	0
SMAD4	0.003	0.042	-10000	0	-0.53	1	1
CBFB	0.014	0	-10000	0	-10000	0	0
SAP18	0.015	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.004	0.074	-10000	0	-0.54	8	8
SMAD3/SMAD4/VDR	0.005	0.041	-10000	0	-10000	0	0
MYC	0.027	0.033	-10000	0	-10000	0	0
CDKN2B	-0.24	0.57	-10000	0	-1.3	102	102
AP1	-0.002	0.1	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.057	0.04	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.062	0.16	-10000	0	-0.56	15	15
SP3	0.016	0	-10000	0	-10000	0	0
CREB1	0.014	0	-10000	0	-10000	0	0
FOXH1	-0.1	0.29	-10000	0	-0.81	69	69
SMAD3/SMAD4/GR	0.03	0.064	-10000	0	-10000	0	0
GATA3	-0.015	0.15	-10000	0	-0.77	19	19
SKI/SIN3/HDAC complex/NCoR1	0.056	0.023	-10000	0	-10000	0	0
MEF2C/TIF2	-0.16	0.28	-10000	0	-0.77	49	49
endothelial cell migration	0.36	0.33	0.65	287	-10000	0	287
MAX	0.035	0.02	-10000	0	-10000	0	0
RBBP7	0.015	0.002	-10000	0	-10000	0	0
RBBP4	0.014	0.026	-10000	0	-0.57	1	1
RUNX2	0.01	0.052	-10000	0	-0.65	3	3
RUNX3	0.004	0.091	-10000	0	-0.82	6	6
RUNX1	0.014	0	-10000	0	-10000	0	0
CTBP1	0.014	0	-10000	0	-10000	0	0
NR3C1	0.035	0.02	-10000	0	-10000	0	0
VDR	0.011	0.037	-10000	0	-0.57	2	2
CDKN1A	0.023	0.093	-10000	0	-10000	0	0
KAT2B	-0.018	0.12	-10000	0	-0.57	24	24
SMAD2/SMAD2/SMAD4/FOXH1	-0.07	0.2	-10000	0	-0.56	69	69
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	287	287
SMAD3/SMAD4/ATF2	0.008	0.046	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.002	0.074	-10000	0	-0.5	6	6
SAP30	0.013	0.037	-10000	0	-0.82	1	1
Cbp/p300/PIAS3	0.002	0.037	-10000	0	-10000	0	0
JUN	0.019	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.014	0.12	-10000	0	-0.59	17	17
TFE3	0	0.019	-10000	0	-10000	0	0
COL1A2	-0.25	0.34	-10000	0	-0.69	185	185
mesenchymal cell differentiation	-0.006	0.056	0.6	1	-10000	0	1
DLX1	-0.33	0.41	-10000	0	-0.82	204	204
TCF3	0.014	0	-10000	0	-10000	0	0
FOS	-0.055	0.19	-10000	0	-0.56	64	64
SMAD3/SMAD4/Max	0.03	0.064	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.003	0.025	-10000	0	-10000	0	0
ZBTB17	0.024	0.026	-10000	0	-10000	0	0
LAMC1	0.011	0.042	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.007	0.058	-10000	0	-0.6	2	2
IRF7	-0.018	0.16	-10000	0	-0.8	19	19
ESR1	-0.016	0.18	-10000	0	-0.69	31	31
HNF4A	-0.07	0.24	-10000	0	-0.82	48	48
MEF2C	-0.14	0.27	-10000	0	-0.64	64	64
SMAD2-3/SMAD4	-0.003	0.057	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.005	0.029	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.012	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0.053	-10000	0	-0.82	2	2
CREBBP	0.008	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	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0	0.045	-10000	0	-10000	0	0
MSG1/HSC70	0.008	0.083	-10000	0	-0.63	8	8
SMAD2	0.002	0.037	-10000	0	-10000	0	0
SMAD3	0.007	0.04	-10000	0	-0.52	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.021	0.046	-10000	0	-0.44	1	1
SMAD2/SMAD2/SMAD4	-0.022	0.079	-10000	0	-0.35	25	25
NCOR1	0.015	0.002	-10000	0	-10000	0	0
NCOA2	-0.031	0.15	-10000	0	-0.57	38	38
NCOA1	0.014	0	-10000	0	-10000	0	0
MYOD/E2A	-0.069	0.16	-10000	0	-0.42	82	82
SMAD2-3/SMAD4/SP1/MIZ-1	-0.03	0.094	-10000	0	-10000	0	0
IFNB1	0.004	0.16	-10000	0	-0.61	24	24
SMAD3/SMAD4/MEF2C	-0.14	0.26	-10000	0	-0.7	41	41
CITED1	0	0.1	-10000	0	-0.82	8	8
SMAD2-3/SMAD4/ARC105	0.005	0.057	-10000	0	-0.48	1	1
RBL1	0.013	0.026	-10000	0	-0.57	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.062	0.22	-10000	0	-0.49	100	100
RUNX1-3/PEBPB2	-0.007	0.059	-10000	0	-0.54	6	6
SMAD7	-0.02	0.11	-10000	0	-10000	0	0
MYC/MIZ-1	0.033	0.065	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.12	0.16	0.36	4	-0.39	6	10
IL10	0.015	0.15	-10000	0	-0.63	17	17
PIASy/HDAC complex	0.023	0.013	-10000	0	-10000	0	0
PIAS3	0.008	0.008	-10000	0	-10000	0	0
CDK2	0.007	0.01	-10000	0	-10000	0	0
IL5	0.012	0.13	-10000	0	-0.58	13	13
CDK4	0.008	0.011	-10000	0	-10000	0	0
PIAS4	0.023	0.013	-10000	0	-10000	0	0
ATF3	0.003	0.086	-10000	0	-0.66	8	8
SMAD3/SMAD4/SP1	-0.047	0.09	-10000	0	-10000	0	0
FOXG1	-0.12	0.28	-10000	0	-0.73	83	83
FOXO3	0.008	0.044	-10000	0	-10000	0	0
FOXO1	0.008	0.043	-10000	0	-10000	0	0
FOXO4	0.006	0.05	-10000	0	-0.4	2	2
heart looping	-0.13	0.27	-10000	0	-0.62	64	64
CEBPB	0.007	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.23	0.29	-10000	0	-0.57	201	201
MYOD1	-0.09	0.22	-10000	0	-0.58	82	82
SMAD3/SMAD4/HNF4	-0.048	0.18	-10000	0	-0.56	48	48
SMAD3/SMAD4/GATA3	-0.013	0.12	-10000	0	-0.56	16	16
SnoN/SIN3/HDAC complex/NCoR1	0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.011	0.066	-10000	0	-0.47	6	6
SMAD3/SMAD4/SP1-3	-0.025	0.082	-10000	0	-10000	0	0
MED15	0.012	0.037	-10000	0	-0.82	1	1
SP1	-0.034	0.074	-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	133	133
ITGB5	0.01	0.09	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.084	0.17	-10000	0	-0.47	19	19
AR	-0.14	0.26	-10000	0	-0.57	132	132
negative regulation of cell growth	0.023	0.055	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.055	0.15	-10000	0	-0.48	16	16
E2F5	0.01	0.045	-10000	0	-0.57	3	3
E2F4	0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.06	0.17	-10000	0	-0.48	69	69
SMAD2-3/SMAD4/FOXO1-3a-4	-0.031	0.15	-10000	0	-10000	0	0
TFDP1	0.012	0.037	-10000	0	-0.82	1	1
SMAD3/SMAD4/AP1	0.002	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.006	0.056	-10000	0	-0.61	1	1
TGIF2	0.01	0.053	-10000	0	-0.82	2	2
TGIF1	0.012	0.037	-10000	0	-0.82	1	1
ATF2	0.013	0.026	-10000	0	-0.57	1	1

×

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	0.029	0.033	-9999	-10000	0	0
SNTA1	0.012	0.037	-9999	-0.82	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.024	0.061	-9999	-0.54	4	4
MAPK12	-0.008	0.14	-9999	-0.56	21	21
CCND1	0	0.088	-9999	-0.39	13	13
p38 gamma/SNTA1	-0.002	0.13	-9999	-0.52	22	22
MAP2K3	0.013	0.026	-9999	-0.57	1	1
PKN1	0.01	0.053	-9999	-0.82	2	2
G2/M transition checkpoint	-0.008	0.14	-9999	-0.55	21	21
MAP2K6	0.005	0.086	-9999	-0.34	26	26
MAPT	-0.13	0.18	-9999	-0.32	221	221
MAPK13	0.021	0.038	-9999	-0.41	4	4
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.016	0.03	-9999	-0.36	3	3

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.076	-9999	-0.6	8	8
alphaV beta3 Integrin	-0.035	0.13	-9999	-0.56	23	23
PTK2	-0.004	0.15	-9999	-0.59	9	9
IGF1R	0.014	0	-9999	-10000	0	0
PI4KB	0.014	0	-9999	-10000	0	0
MFGE8	0.012	0.037	-9999	-0.82	1	1
SRC	0.014	0	-9999	-10000	0	0
CDKN1B	-0.036	0.1	-9999	-0.41	31	31
VEGFA	0.004	0.091	-9999	-0.82	6	6
ILK	-0.036	0.1	-9999	-0.41	31	31
ROCK1	0.014	0	-9999	-10000	0	0
AKT1	0.001	0.11	-9999	-0.5	3	3
PTK2B	0.013	0.12	-9999	-0.46	25	25
alphaV/beta3 Integrin/JAM-A	-0.059	0.16	-9999	-0.49	51	51
CBL	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.026	0.11	-9999	-0.55	20	20
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.054	0.12	-9999	-0.52	5	5
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.017	0.084	-9999	-0.42	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.023	0.11	-9999	-0.55	17	17
PI4KA	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.26	0.25	-9999	-0.74	48	48
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.31	0.29	-9999	-0.56	274	274
RPS6KB1	-0.21	0.25	-9999	-0.68	48	48
TLN1	0.01	0.053	-9999	-0.82	2	2
MAPK3	-0.11	0.15	-9999	-0.68	16	16
GPR124	0.009	0.064	-9999	-0.82	3	3
MAPK1	-0.11	0.15	-9999	-0.68	16	16
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
alphaV/beta3 Integrin/Tumstatin	-0.081	0.2	-9999	-0.59	56	56
cell adhesion	-0.023	0.1	-9999	-0.49	17	17
ANGPTL3	0	0.064	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.066	-9999	-0.54	7	7
IGF-1R heterotetramer	0.014	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.011	0.037	-9999	-0.57	2	2
ITGB3	-0.015	0.14	-9999	-0.73	19	19
IGF1	-0.088	0.22	-9999	-0.58	85	85
RAC1	0.014	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.026	0.12	-9999	-0.57	19	19
apoptosis	0.006	0.078	-9999	-0.77	5	5
CD47	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.023	0.11	-9999	-0.55	17	17
VCL	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.088	0.2	-9999	-0.58	57	57
CSF1	0.007	0.063	-9999	-0.57	6	6
PIK3C2A	-0.036	0.1	-9999	-0.41	31	31
PI4 Kinase/Pyk2	-0.054	0.14	-9999	-0.77	5	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.028	0.11	-9999	-0.5	25	25
FAK1/Vinculin	0.006	0.12	-9999	-0.49	5	5
alphaV beta3/Integrin/ppsTEM5	-0.026	0.12	-9999	-0.57	19	19
RHOA	0.014	0	-9999	-10000	0	0
VTN	-0.039	0.2	-9999	-0.82	31	31
BCAR1	0.014	0	-9999	-10000	0	0
FGF2	-0.007	0.12	-9999	-0.63	16	16
F11R	0.008	0.089	-9999	-0.46	17	17
alphaV/beta3 Integrin/Lactadherin	-0.024	0.11	-9999	-0.58	17	17
alphaV/beta3 Integrin/TGFBR2	-0.024	0.11	-9999	-0.55	17	17
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.008	0.056	-9999	-0.49	4	4
HSP90AA1	0.014	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.023	0.1	-9999	-0.51	19	19
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.36	0.41	-9999	-0.82	221	221
alphaV/beta3 Integrin/Pyk2	0.013	0.12	-9999	-0.47	25	25
SDC1	0.014	0	-9999	-10000	0	0
VAV3	0.012	0.1	-9999	-0.5	7	7
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.57	3	3
FAK1/Paxillin	0.006	0.12	-9999	-0.49	5	5
cell migration	0.016	0.12	-9999	-0.46	3	3
ITGAV	0.006	0.079	-9999	-0.77	5	5
PI3K	-0.054	0.14	-9999	-0.72	6	6
SPP1	-0.44	0.42	-9999	-0.82	268	268
KDR	0.011	0.045	-9999	-0.69	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.006	0.079	-9999	-0.77	5	5
COL4A3	-0.08	0.25	-9999	-0.74	61	61
angiogenesis	-0.077	0.17	-9999	-0.7	14	14
Rac1/GTP	-0.024	0.082	-9999	-0.52	3	3
EDIL3	-0.091	0.26	-9999	-0.71	72	72
cell proliferation	-0.024	0.11	-9999	-0.55	17	17

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.14	0.27	-9999	-0.59	130	130
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.053	-9999	-0.82	2	2
TCEB1	0.012	0.037	-9999	-0.82	1	1
HIF1A/p53	0.024	0.041	-9999	-10000	0	0
HIF1A	0.019	0.034	-9999	-10000	0	0
COPS5	0.014	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.004	0.041	-9999	-0.46	4	4
FIH (dimer)	0.014	0	-9999	-10000	0	0
CDKN2A	-0.35	0.4	-9999	-0.77	230	230
ARNT/IPAS	-0.11	0.19	-9999	-0.43	130	130
HIF1AN	0.014	0	-9999	-10000	0	0
GNB2L1	0.014	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.032	-9999	-10000	0	0
CUL2	0.012	0.037	-9999	-0.82	1	1
OS9	0.014	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.003	0.042	-9999	-0.54	3	3
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.026	0.032	-9999	-10000	0	0
PHD1-3/OS9	-0.029	0.11	-9999	-0.49	26	26
HIF1A/RACK1/Elongin B/Elongin C	-0.007	0.043	-9999	-0.5	3	3
VHL	0.014	0	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
HIF1A/JAB1	0.026	0.032	-9999	-10000	0	0
EGLN3	-0.036	0.19	-9999	-0.78	31	31
EGLN2	0.014	0	-9999	-10000	0	0
EGLN1	0.014	0	-9999	-10000	0	0
TP53	0.009	0.052	-9999	-0.57	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.037	0.027	-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	189	189

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.008	0.059	-10000	0	-0.58	4	4
HDAC1	0.01	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	0.01	0.052	-10000	0	-0.65	3	3
LRP6/FZD1	-0.008	0.068	-10000	0	-0.56	7	7
TLE1	0.013	0.001	-10000	0	-10000	0	0
AP1	-0.023	0.12	-10000	0	-0.7	3	3
NCSTN	0.014	0	-10000	0	-10000	0	0
ADAM10	0.011	0.037	-10000	0	-0.57	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.046	-10000	0	-10000	0	0
NICD/RBPSUH	-0.005	0.051	-10000	0	-0.57	4	4
WIF1	-0.26	0.3	-10000	0	-0.59	219	219
NOTCH1	-0.005	0.055	-10000	0	-0.61	4	4
PSENEN	0.01	0.053	-10000	0	-0.82	2	2
KREMEN2	-0.29	0.4	-10000	0	-0.82	183	183
DKK1	-0.28	0.39	-10000	0	-0.8	183	183
beta catenin/beta TrCP1	0.021	0.045	-10000	0	-0.34	1	1
APH1B	0.014	0	-10000	0	-10000	0	0
APH1A	0.014	0	-10000	0	-10000	0	0
AXIN1	0.002	0.025	-10000	0	-0.28	1	1
CtBP/CBP/TCF1/TLE1/AES	0.019	0.044	-10000	0	-10000	0	0
PSEN1	0.014	0	-10000	0	-10000	0	0
FOS	-0.061	0.19	-10000	0	-0.57	64	64
JUN	0.014	0	-10000	0	-10000	0	0
MAP3K7	0.012	0.002	-10000	0	-10000	0	0
CTNNB1	0.014	0.047	-10000	0	-0.37	1	1
MAPK3	0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.21	0.27	-10000	0	-0.55	191	191
HNF1A	-0.003	0.11	-10000	0	-0.82	9	9
CTBP1	0.013	0.001	-10000	0	-10000	0	0
MYC	0.025	0.013	-10000	0	-10000	0	0
NKD1	-0.017	0.15	-10000	0	-0.78	19	19
FZD1	0.004	0.087	-10000	0	-0.78	6	6
NOTCH1 precursor/Deltex homolog 1	-0.007	0.063	-10000	0	-0.6	5	5
apoptosis	-0.023	0.12	-10000	0	-0.69	3	3
Delta 1/NOTCHprecursor	-0.008	0.059	-10000	0	-0.57	4	4
DLL1	0.007	0.063	-10000	0	-0.57	6	6
PPARD	0.025	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.002	0.029	-10000	0	-0.46	2	2
APC	0.001	0.031	-10000	0	-0.35	2	2
DVL1	-0.018	0.028	-10000	0	-10000	0	0
CSNK2A1	0.014	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.39	0.36	-10000	0	-0.66	289	289
LRP6	0.013	0.026	-10000	0	-0.57	1	1
CSNK1A1	0.014	0.001	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.006	0.14	-10000	0	-0.84	12	12
WNT1	0.002	0.083	-10000	0	-0.82	5	5
Axin1/APC/beta catenin	0.027	0.042	-10000	0	-0.39	1	1
DKK2	-0.009	0.13	-10000	0	-0.69	16	16
NOTCH1 precursor/DVL1	-0.009	0.051	-10000	0	-0.57	4	4
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.007	0.064	-10000	0	-0.61	5	5
PPP2R5D	0.002	0.066	0.32	19	-10000	0	19
MAPK1	0.014	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.15	0.17	-10000	0	-0.51	27	27
RBPJ	0.014	0	-10000	0	-10000	0	0
CREBBP	0.017	0.003	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.054	0.23	-9999	-0.89	21	21
NCK1/PAK1/Dok-R	-0.028	0.09	-9999	-0.41	21	21
NCK1/Dok-R	-0.052	0.22	-9999	-1.1	21	21
PIK3CA	0.013	0.001	-9999	-10000	0	0
mol:beta2-estradiol	-0.005	0.041	-9999	-10000	0	0
RELA	0.014	0	-9999	-10000	0	0
SHC1	0.014	0.002	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
F2	-0.079	0.25	-9999	-0.84	47	47
TNIP2	0.014	0	-9999	-10000	0	0
NF kappa B/RelA	-0.046	0.2	-9999	-0.99	21	21
FN1	-0.36	0.41	-9999	-0.82	221	221
PLD2	0.031	0.25	-9999	-1.1	21	21
PTPN11	0.014	0	-9999	-10000	0	0
GRB14	-0.045	0.18	-9999	-0.6	47	47
ELK1	0.045	0.23	-9999	-0.99	21	21
GRB7	0.005	0.083	-9999	-0.74	6	6
PAK1	0.012	0.037	-9999	-0.82	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.34	0.36	-9999	-0.86	131	131
CDKN1A	0.061	0.19	-9999	-0.65	11	11
ITGA5	-0.25	0.39	-9999	-0.82	155	155
mol:GTP	0	0	-9999	-10000	0	0
RasGAP/Dok-R	-0.054	0.22	-9999	-1.1	21	21
CRK	0.014	0	-9999	-10000	0	0
mol:NO	0.058	0.18	-9999	-0.64	21	21
PLG	0.02	0.25	-9999	-1.1	21	21
mol:GDP	0	0	-9999	-10000	0	0
chemokinesis	0.034	0.21	-9999	-0.85	21	21
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.011	0.045	-9999	-0.57	3	3
ANGPT2	0.018	0.19	-9999	-0.61	24	24
BMX	-0.006	0.28	-9999	-1.2	21	21
ANGPT1	0.015	0.23	-9999	-1.2	14	14
tube development	0.054	0.21	-9999	-0.74	12	12
ANGPT4	0.008	0.008	-9999	-10000	0	0
response to hypoxia	0.001	0.015	-9999	-10000	0	0
Tie2/Ang1/GRB14	-0.004	0.27	-9999	-1.2	21	21
alpha5/beta1 Integrin	-0.2	0.29	-9999	-0.63	156	156
FGF2	-0.008	0.12	-9999	-0.63	16	16
STAT5A (dimer)	0.056	0.23	-9999	-0.85	11	11
mol:L-citrulline	0.058	0.18	-9999	-0.64	21	21
AGTR1	-0.042	0.17	-9999	-0.58	46	46
MAPK14	0.034	0.26	-9999	-1.1	21	21
Tie2/SHP2	-0.032	0.18	-9999	-1.2	11	11
TEK	0.011	0.21	-9999	-1.3	11	11
RPS6KB1	0.057	0.22	-9999	-0.85	21	21
Angiotensin II/AT1	-0.029	0.13	-9999	-0.43	46	46
Tie2/Ang1/GRB2	0.027	0.26	-9999	-1.2	21	21
MAPK3	0.04	0.23	-9999	-1	21	21
MAPK1	0.04	0.23	-9999	-1	21	21
Tie2/Ang1/GRB7	0.022	0.27	-9999	-1.2	21	21
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.027	0.26	-9999	-1.1	21	21
PI3K	0.045	0.25	-9999	-1	21	21
FES	0.034	0.26	-9999	-1.1	21	21
Crk/Dok-R	-0.052	0.22	-9999	-1.1	21	21
Tie2/Ang1/ABIN2	0.027	0.26	-9999	-1.2	21	21
blood circulation	0	0	-9999	-10000	0	0
negative regulation of caspase activity	0.057	0.21	-9999	-0.79	21	21
STAT5A	0.014	0	-9999	-10000	0	0
mol:ROS	0	0	-9999	-10000	0	0
PTK2	0.057	0.22	-9999	-0.85	21	21
Tie2/Ang2	0.039	0.26	-9999	-1.1	11	11
Tie2/Ang1	0.023	0.28	-9999	-1.2	21	21
FOXO1	0.058	0.22	-9999	-0.79	21	21
ELF1	0.017	0.056	-9999	-0.58	4	4
ELF2	0.028	0.25	-9999	-1.1	21	21
mol:Choline	0.033	0.24	-9999	-1.1	21	21
cell migration	-0.09	0.087	-9999	-10000	0	0
FYN	0.05	0.23	-9999	-0.86	12	12
DOK2	0.008	0.069	-9999	-0.76	4	4
negative regulation of cell cycle	0.063	0.18	-9999	-0.59	11	11
ETS1	0.013	0.074	-9999	-0.8	3	3
PXN	0.067	0.19	-9999	-0.7	21	21
ITGB1	0.012	0.037	-9999	-0.82	1	1
NOS3	0.056	0.2	-9999	-0.74	21	21
RAC1	0.014	0	-9999	-10000	0	0
TNF	-0.019	0.18	-9999	-0.78	24	24
MAPKKK cascade	0.033	0.24	-9999	-1.1	21	21
RASA1	0.011	0.037	-9999	-0.57	2	2
Tie2/Ang1/Shc	0.028	0.26	-9999	-1.2	21	21
NCK1	0.014	0	-9999	-10000	0	0
vasculogenesis	0.06	0.17	-9999	-0.58	21	21
mol:Phosphatidic acid	0.033	0.24	-9999	-1.1	21	21
mol:Angiotensin II	0	0.007	-9999	-10000	0	0
mol:NADP	0.058	0.18	-9999	-0.64	21	21
Rac1/GTP	-0.048	0.17	-9999	-0.79	21	21
MMP2	-0.037	0.3	-9999	-1.1	21	21

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.038	0.16	-9999	-0.73	11	11
FZD6	0.011	0.045	-9999	-0.69	2	2
WNT6	-0.052	0.22	-9999	-0.76	42	42
WNT4	-0.007	0.12	-9999	-0.63	16	16
FZD3	0.006	0.068	-9999	-0.57	7	7
WNT5A	0.005	0.073	-9999	-0.6	7	7
WNT11	-0.074	0.25	-9999	-0.75	57	57

×

LPA receptor mediated 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
GNB1/GNG2	-0.043	0.1	-9999	-0.78	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.055	-9999	-0.42	1	1
AP1	-0.072	0.13	-9999	-0.55	13	13
mol:PIP3	-0.05	0.11	-9999	-0.56	6	6
AKT1	0.026	0.088	-9999	-0.51	2	2
PTK2B	0	0.076	-9999	-0.29	6	6
RHOA	0.011	0.058	-9999	-0.31	1	1
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.01	0.074	-9999	-0.49	3	3
MAGI3	0.011	0.037	-9999	-0.57	2	2
RELA	0.014	0	-9999	-10000	0	0
apoptosis	-0.019	0.11	-9999	-0.61	4	4
HRAS/GDP	-0.001	0.029	-9999	-0.64	1	1
positive regulation of microtubule depolymerization	-0.11	0.15	-9999	-0.41	31	31
NF kappa B1 p50/RelA	-0.033	0.089	-9999	-0.54	5	5
endothelial cell migration	-0.089	0.28	-9999	-0.76	70	70
ADCY4	-0.006	0.12	-9999	-0.43	16	16
ADCY5	-0.053	0.14	-9999	-0.52	18	18
ADCY6	-0.011	0.13	-9999	-0.46	17	17
ADCY7	-0.006	0.12	-9999	-0.43	16	16
ADCY1	-0.014	0.12	-9999	-0.43	17	17
ADCY2	-0.073	0.14	-9999	-0.48	23	23
ADCY3	-0.006	0.12	-9999	-0.43	16	16
ADCY8	-0.013	0.12	-9999	-0.42	20	20
ADCY9	-0.007	0.12	-9999	-0.43	16	16
GSK3B	0.008	0.073	-9999	-10000	0	0
arachidonic acid secretion	0.001	0.12	-9999	-0.41	16	16
GNG2	0.012	0.037	-9999	-0.82	1	1
TRIP6	0.018	0.022	-9999	-10000	0	0
GNAO1	-0.026	0.13	-9999	-0.42	16	16
HRAS	0.012	0.037	-9999	-0.82	1	1
NFKBIA	0.015	0.087	-9999	-0.44	3	3
GAB1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.008	0.1	-9999	-0.89	7	7
JUN	0.014	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.014	0.05	-9999	-0.64	2	2
TIAM1	-0.012	0.12	-9999	-1	7	7
PIK3R1	0.01	0.045	-9999	-0.57	3	3
mol:IP3	0.01	0.075	-9999	-0.5	3	3
PLCB3	0.015	0.051	-9999	-0.58	2	2
FOS	-0.061	0.19	-9999	-0.57	64	64
positive regulation of mitosis	0.001	0.12	-9999	-0.41	16	16
LPA/LPA1-2-3	-0.049	0.11	-9999	-0.64	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0	-9999	-10000	0	0
stress fiber formation	0.005	0.089	-9999	-0.41	3	3
GNAZ	-0.042	0.16	-9999	-0.48	31	31
EGFR/PI3K-beta/Gab1	-0.052	0.11	-9999	-0.59	6	6
positive regulation of dendritic cell cytokine production	-0.049	0.11	-9999	-0.64	4	4
LPA/LPA2/MAGI-3	-0.014	0.037	-9999	-0.34	2	2
ARHGEF1	-0.004	0.11	-9999	-0.64	3	3
GNAI2	-0.022	0.12	-9999	-0.38	12	12
GNAI3	-0.022	0.12	-9999	-0.4	8	8
GNAI1	-0.023	0.12	-9999	-0.38	13	13
LPA/LPA3	-0.027	0.075	-9999	-0.42	12	12
LPA/LPA2	-0.017	0.042	-9999	-10000	0	0
LPA/LPA1	-0.058	0.14	-9999	-0.36	81	81
HB-EGF/EGFR	-0.41	0.27	-9999	-0.56	368	368
HBEGF	-0.46	0.29	-9999	-0.63	366	366
mol:DAG	0.01	0.075	-9999	-0.5	3	3
cAMP biosynthetic process	-0.02	0.12	-9999	-0.48	14	14
NFKB1	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.015	0.087	-9999	-0.46	2	2
GNAQ	0.005	0.059	-9999	-0.32	3	3
LPAR2	0.014	0	-9999	-10000	0	0
LPAR3	0	0.089	-9999	-0.57	12	12
LPAR1	-0.023	0.11	-9999	-0.6	12	12
IL8	-0.23	0.18	-9999	-0.5	95	95
PTK2	-0.01	0.12	-9999	-0.6	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.019	0.11	-9999	-0.61	4	4
EGFR	-0.017	0.15	-9999	-0.76	20	20
PLCG1	-0.006	0.077	-9999	-0.32	12	12
PLD2	-0.01	0.12	-9999	-0.6	4	4
G12/G13	-0.044	0.1	-9999	-0.68	3	3
PI3K-beta	-0.031	0.076	-9999	-0.56	3	3
cell migration	-0.011	0.047	-9999	-0.28	1	1
SLC9A3R2	0.01	0.053	-9999	-0.82	2	2
PXN	0.004	0.09	-9999	-0.42	3	3
HRAS/GTP	0	0.12	-9999	-0.42	16	16
RAC1	0.014	0	-9999	-10000	0	0
MMP9	-0.6	0.37	-9999	-0.82	366	366
PRKCE	0.012	0.026	-9999	-0.57	1	1
PRKCD	0.018	0.072	-9999	-0.52	2	2
Gi(beta/gamma)	-0.002	0.12	-9999	-0.4	17	17
mol:LPA	-0.024	0.072	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.027	0.085	-9999	-0.54	3	3
MAPKKK cascade	0.001	0.12	-9999	-0.41	16	16
contractile ring contraction involved in cytokinesis	0.011	0.057	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.043	0.12	-9999	-0.32	22	22
GNA15	0.004	0.066	-9999	-0.53	2	2
GNA12	0.01	0.053	-9999	-0.82	2	2
GNA13	0.014	0	-9999	-10000	0	0
MAPT	-0.11	0.16	-9999	-0.42	31	31
GNA11	0.003	0.066	-9999	-0.33	5	5
Rac1/GTP	-0.009	0.11	-9999	-0.94	7	7
MMP2	-0.09	0.28	-9999	-0.76	70	70

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.14	0.32	-10000	0	-0.82	89	89
Jak2/Leptin Receptor	-0.07	0.1	-10000	0	-0.42	8	8
PTP1B/AKT1	-0.02	0.083	0.23	1	-0.34	3	4
FYN	0.012	0.037	-10000	0	-0.82	1	1
p210 bcr-abl/PTP1B	-0.03	0.092	0.26	1	-0.35	8	9
EGFR	-0.02	0.15	-10000	0	-0.76	20	20
EGF/EGFR	-0.1	0.15	-10000	0	-0.44	47	47
CSF1	0.007	0.063	-10000	0	-0.57	6	6
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.013	0.026	-10000	0	-0.57	1	1
PTP1B/N-cadherin	-0.082	0.2	-10000	0	-0.54	65	65
Insulin Receptor/Insulin	-0.032	0.056	-10000	0	-0.43	2	2
HCK	0.006	0.079	-10000	0	-0.77	5	5
CRK	0.014	0	-10000	0	-10000	0	0
TYK2	-0.021	0.091	0.25	1	-0.4	4	5
EGF	-0.096	0.23	-10000	0	-0.58	91	91
YES1	0.014	0	-10000	0	-10000	0	0
CAV1	-0.044	0.11	0.25	1	-0.37	15	16
TXN	0.011	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.015	0.085	-10000	0	-0.36	2	2
cell migration	0.03	0.092	0.35	8	-0.26	1	9
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.12	0.24	-10000	0	-0.57	109	109
ITGA2B	-0.066	0.24	-10000	0	-0.82	47	47
CSF1R	0.01	0.045	-10000	0	-0.57	3	3
Prolactin Receptor/Prolactin	-0.095	0.19	-10000	0	-0.43	112	112
FGR	0.012	0.037	-10000	0	-0.82	1	1
PTP1B/p130 Cas	-0.021	0.087	-10000	0	-0.35	6	6
Crk/p130 Cas	-0.013	0.083	-10000	0	-0.36	2	2
DOK1	-0.05	0.14	0.25	1	-0.36	37	38
JAK2	-0.063	0.12	-10000	0	-0.37	26	26
Jak2/Leptin Receptor/Leptin	-0.074	0.12	-10000	0	-0.48	3	3
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
PTPN1	-0.03	0.093	0.26	1	-0.35	8	9
LYN	0.012	0.037	-10000	0	-0.82	1	1
CDH2	-0.093	0.27	-10000	0	-0.79	66	66
SRC	0.005	0.038	-10000	0	-10000	0	0
ITGB3	-0.015	0.14	-10000	0	-0.73	19	19
CAT1/PTP1B	-0.11	0.14	0.26	1	-0.43	24	25
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.014	0	-10000	0	-10000	0	0
PI3K	-0.024	0.057	-10000	0	-0.46	2	2
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.066	0.1	-10000	0	-10000	0	0
negative regulation of transcription	-0.062	0.12	-10000	0	-0.37	26	26
FCGR2A	-0.028	0.18	-10000	0	-0.82	25	25
FER	0.008	0.037	-10000	0	-0.57	2	2
alphaIIb/beta3 Integrin	-0.079	0.21	-10000	0	-0.63	63	63
BLK	-0.1	0.28	-10000	0	-0.78	71	71
Insulin Receptor/Insulin/Shc	-0.003	0.037	-10000	0	-0.47	3	3
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	0.01	0.045	-10000	0	-0.56	3	3
BCAR1	0.014	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.014	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.1	0.14	-10000	0	-0.42	35	35
PRL	-0.004	0.082	-10000	0	-0.82	5	5
SOCS3	0.018	0.063	-10000	0	-1.3	1	1
SPRY2	0.004	0.074	-10000	0	-0.57	8	8
Insulin Receptor/Insulin/IRS1	-0.005	0.046	-10000	0	-0.41	6	6
CSF1/CSF1R	-0.018	0.093	-10000	0	-0.39	7	7
Ras protein signal transduction	0.026	0.029	-10000	0	-10000	0	0
IRS1	0.01	0.045	-10000	0	-0.57	3	3
INS	-0.003	0.052	-10000	0	-0.82	2	2
LEP	-0.096	0.25	-10000	0	-0.66	78	78
STAT5B	-0.039	0.088	0.21	1	-0.32	12	13
STAT5A	-0.039	0.088	0.21	1	-0.32	12	13
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.11	0.23	0.23	1	-0.56	93	94
CSN2	-0.027	0.092	-10000	0	-0.75	2	2
PIK3CA	0.014	0	-10000	0	-10000	0	0
LAT	-0.017	0.089	-10000	0	-0.32	28	28
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.006	0.13	-10000	0	-0.82	12	12
SHC1	0.014	0	-10000	0	-10000	0	0
NOX4	-0.16	0.34	-10000	0	-0.82	102	102

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.053	0.19	-9999	-0.4	108	108
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.012	0.037	-9999	-0.82	1	1
STAT1 (dimer)/Cbp/p300	-0.09	0.19	-9999	-0.72	20	20
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	-0.071	0.09	-9999	-0.33	9	9
CaM/Ca2+	-0.082	0.15	-9999	-10000	0	0
RAP1A	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.066	0.23	-9999	-0.71	27	27
AKT1	-0.025	0.16	-9999	-10000	0	0
MAP2K1	-0.03	0.17	-9999	-10000	0	0
MAP3K11	-0.043	0.18	-9999	-10000	0	0
IFNGR1	0.007	0.017	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.19	0.23	-9999	-0.61	81	81
Rap1/GTP	-0.062	0.12	-9999	-10000	0	0
CRKL/C3G	-0.001	0.028	-9999	-0.63	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.097	0.18	-9999	-0.44	109	109
CEBPB	0.01	0.15	-9999	-10000	0	0
STAT3	0.014	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.1	0.24	-9999	-0.92	17	17
STAT1	-0.066	0.23	-9999	-0.71	27	27
CALM1	0.014	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.16	0.34	-9999	-0.81	108	108
PIK3CA	0.014	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.054	0.22	-9999	-0.77	19	19
CEBPB/PTGES2/Cbp/p300	-0.039	0.071	-9999	-10000	0	0
mol:Ca2+	-0.087	0.16	-9999	-0.4	108	108
MAPK3	-0.009	0.15	-9999	-10000	0	0
STAT1 (dimer)	-0.094	0.12	-9999	-0.46	9	9
MAPK1	-0.009	0.15	-9999	-10000	0	0
JAK2	0.006	0.031	-9999	-0.56	1	1
PIK3R1	0.01	0.045	-9999	-0.57	3	3
JAK1	0.007	0.017	-9999	-10000	0	0
CAMK2D	0.014	0	-9999	-10000	0	0
DAPK1	0.024	0.12	-9999	-0.57	5	5
SMAD7	-0.002	0.074	-9999	-10000	0	0
CBL/CRKL/C3G	-0.074	0.14	-9999	-10000	0	0
PI3K	-0.08	0.15	-9999	-10000	0	0
IFNG	-0.16	0.34	-9999	-0.81	108	108
apoptosis	0.008	0.1	-9999	-0.44	4	4
CAMK2G	0.014	0	-9999	-10000	0	0
STAT3 (dimer)	0.014	0	-9999	-10000	0	0
CAMK2A	-0.13	0.25	-9999	-0.57	122	122
CAMK2B	-0.14	0.26	-9999	-0.58	127	127
FRAP1	-0.022	0.15	-9999	-10000	0	0
PRKCD	-0.024	0.16	-9999	-10000	0	0
RAP1B	0.012	0.037	-9999	-0.82	1	1
negative regulation of cell growth	-0.071	0.09	-9999	-0.33	9	9
PTPN2	0.012	0.037	-9999	-0.82	1	1
EP300	0.012	0.037	-9999	-0.56	2	2
IRF1	-0.025	0.19	-9999	-0.52	35	35
STAT1 (dimer)/PIASy	-0.091	0.2	-9999	-0.77	19	19
SOCS1	-0.043	0.18	-9999	-0.66	38	38
mol:GDP	-0.072	0.14	-9999	-10000	0	0
CASP1	-0.003	0.075	-9999	-0.33	1	1
PTGES2	0.014	0	-9999	-10000	0	0
IRF9	0.036	0.057	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.078	0.14	-9999	-10000	0	0
RAP1/GDP	-0.063	0.12	-9999	-10000	0	0
CBL	-0.044	0.18	-9999	-10000	0	0
MAP3K1	-0.042	0.18	-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	-0.071	0.09	-9999	-0.33	9	9
PTPN11	-0.054	0.18	-9999	-0.4	108	108
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.14	0.3	-9999	-0.68	108	108
RAD9A	0.014	0	-9999	-10000	0	0
AP1	-0.037	0.14	-9999	-0.41	64	64
IFNAR2	0.012	0.007	-9999	-10000	0	0
AKT1	-0.002	0.068	-9999	-0.3	11	11
ER alpha/Oestrogen	-0.025	0.13	-9999	-0.53	31	31
NFX1/SIN3/HDAC complex	0.04	0.028	-9999	-10000	0	0
EGF	-0.096	0.23	-9999	-0.57	91	91
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	-0.16	0.26	-9999	-0.63	108	108
SAP18	0.013	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.16	0.34	-9999	-0.82	103	103
WRN	0.014	0	-9999	-10000	0	0
SP1	0.013	0.007	-9999	-10000	0	0
SP3	0.011	0.006	-9999	-10000	0	0
TERF2IP	0.014	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.14	0.23	-9999	-0.6	81	81
Mad/Max	0.013	0.044	-9999	-0.41	5	5
TERT	-0.15	0.31	-9999	-0.7	108	108
CCND1	-0.13	0.29	-9999	-0.72	49	49
MAX	0.012	0.006	-9999	-10000	0	0
RBBP7	0.013	0.004	-9999	-10000	0	0
RBBP4	0.011	0.026	-9999	-0.57	1	1
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.014	0	-9999	-10000	0	0
SIN3A	0.013	0.004	-9999	-10000	0	0
Telomerase/911	0.025	0.043	-9999	-0.34	1	1
CDKN1B	-0.087	0.23	-9999	-0.52	108	108
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	0.011	0.038	-9999	-0.82	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.011	0.006	-9999	-10000	0	0
JUN	0.012	0.006	-9999	-10000	0	0
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.01	0.006	-9999	-10000	0	0
FOS	-0.063	0.19	-9999	-0.57	64	64
IFN-gamma/IRF1	-0.13	0.25	-9999	-0.62	108	108
PARP2	0.014	0	-9999	-10000	0	0
BLM	0.01	0.053	-9999	-0.82	2	2
Telomerase	-0.004	0.11	-9999	-0.39	23	23
IRF1	0.016	0.008	-9999	-10000	0	0
ESR1	-0.032	0.18	-9999	-0.7	31	31
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.016	-9999	-0.36	1	1
ubiquitin-dependent protein catabolic process	0.044	0.029	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.044	0.029	-9999	-10000	0	0
HDAC1	0.013	0.004	-9999	-10000	0	0
HDAC2	0.013	0.007	-9999	-10000	0	0
ATM	-0.001	0.019	-9999	-0.43	1	1
SMAD3	0.023	0.046	-9999	-0.56	3	3
ABL1	0.014	0	-9999	-10000	0	0
MXD1	0.006	0.058	-9999	-0.57	5	5
MRE11A	0.014	0	-9999	-10000	0	0
HUS1	0.012	0.037	-9999	-0.82	1	1
RPS6KB1	0.014	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.26	-9999	-0.63	83	83
NR2F2	0.015	0.038	-9999	-0.81	1	1
MAPK3	0.013	0.03	-9999	-0.62	1	1
MAPK1	0.013	0.03	-9999	-0.62	1	1
TGFB1/TGF beta receptor Type II	0.011	0.053	-9999	-0.82	2	2
NFKB1	0.014	0	-9999	-10000	0	0
HNRNPC	0.014	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.019	-9999	-0.43	1	1
NBN	0.014	0	-9999	-10000	0	0
EGFR	-0.019	0.15	-9999	-0.76	20	20
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.091	0.2	-9999	-0.45	108	108
MYC	0.012	0.006	-9999	-10000	0	0
IL2	0.001	0.039	-9999	-0.82	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	0.011	0.053	-9999	-0.82	2	2
TRF2/BLM	-0.002	0.038	-9999	-0.59	2	2
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.14	0.27	-9999	-0.66	84	84
SP1/HDAC2	0.02	0.015	-9999	-10000	0	0
PINX1	0.014	0	-9999	-10000	0	0
Telomerase/EST1A	-0.14	0.23	-9999	-0.61	70	70
Smad3/Myc	0.027	0.04	-9999	-0.54	2	2
911 complex	-0.001	0.024	-9999	-0.54	1	1
IFNG	-0.16	0.34	-9999	-0.81	108	108
Telomerase/PinX1	-0.14	0.23	-9999	-0.61	71	71
Telomerase/AKT1/mTOR/p70S6K	0	0.076	-9999	-10000	0	0
SIN3B	0.013	0.004	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
Telomerase/EST1B	-0.14	0.23	-9999	-0.61	71	71
response to DNA damage stimulus	0.003	0.006	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.23	-9999	-0.6	81	81
E2F1	-0.05	0.22	-9999	-0.83	37	37
ZNFX1	0.013	0.004	-9999	-10000	0	0
PIF1	-0.033	0.19	-9999	-0.82	28	28
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

×

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	0.006	0.078	-9999	-0.56	9	9
HDAC7	-0.066	0.16	-9999	-0.57	20	20
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.011	0.037	-9999	-0.57	2	2
KAT2B	-0.015	0.12	-9999	-0.57	24	24
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.009	0.1	-9999	-0.43	26	26
FOXO1	0.013	0.001	-9999	-10000	0	0
T-DHT/AR	-0.08	0.17	-9999	-0.6	21	21
MAP2K6	-0.023	0.13	-9999	-0.58	26	26
BRM/BAF57	-0.001	0.018	-9999	-0.41	1	1
MAP2K4	0.008	0.008	-9999	-10000	0	0
SMARCA2	0.01	0.026	-9999	-0.57	1	1
PDE9A	-0.091	0.21	-9999	-1.1	16	16
NCOA2	-0.031	0.15	-9999	-0.57	38	38
CEBPA	0.011	0.045	-9999	-0.56	3	3
EHMT2	0.011	0.005	-9999	-10000	0	0
cell proliferation	-0.059	0.17	-9999	-0.56	10	10
NR0B1	-0.033	0.17	-9999	-0.82	23	23
EGR1	-0.017	0.12	-9999	-0.57	24	24
RXRs/9cRA	-0.041	0.11	-9999	-0.34	60	60
AR/RACK1/Src	-0.035	0.12	-9999	-0.51	8	8
AR/GR	-0.062	0.15	-9999	-0.52	18	18
GNB2L1	0.014	0.001	-9999	-10000	0	0
PKN1	0.01	0.053	-9999	-0.82	2	2
RCHY1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.008	0.055	-9999	-0.44	7	7
T-DHT/AR/TIF2/CARM1	-0.049	0.16	-9999	-0.65	11	11
SRC	-0.002	0.095	-9999	-0.59	2	2
NR3C1	0.014	0	-9999	-10000	0	0
KLK3	-0.28	0.45	-9999	-1.2	92	92
APPBP2	0.008	0.008	-9999	-10000	0	0
TRIM24	0.01	0.026	-9999	-0.57	1	1
T-DHT/AR/TIP60	-0.036	0.13	-9999	-0.51	18	18
TMPRSS2	-0.52	0.55	-9999	-1.1	237	237
RXRG	-0.063	0.2	-9999	-0.6	60	60
mol:9cRA	-0.001	0.003	-9999	-10000	0	0
RXRA	0.013	0.001	-9999	-10000	0	0
RXRB	0.013	0.001	-9999	-10000	0	0
CARM1	0.014	0.002	-9999	-10000	0	0
NR2C2	0.005	0.068	-9999	-0.57	7	7
KLK2	-0.035	0.16	-9999	-0.62	19	19
AR	-0.078	0.16	-9999	-0.38	71	71
SENP1	0.013	0.001	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
MDM2	0.018	0.012	-9999	-10000	0	0
SRY	-0.034	0.16	-9999	-0.58	38	38
GATA2	0.006	0.079	-9999	-0.77	5	5
MYST2	0.013	0.026	-9999	-0.57	1	1
HOXB13	-0.3	0.4	-9999	-0.83	182	182
T-DHT/AR/RACK1/Src	-0.027	0.12	-9999	-0.53	6	6
positive regulation of transcription	0.006	0.079	-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	-0.17	0.28	-9999	-0.6	144	144
T-DHT/AR/TIF2	-0.032	0.15	-9999	-0.6	15	15
T-DHT/AR/Hsp90	-0.037	0.12	-9999	-0.51	18	18
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.002	-9999	-10000	0	0
mol:T-DHT	-0.012	0.1	-9999	-0.51	4	4
SIRT1	0.012	0.026	-9999	-0.57	1	1
ZMIZ2	0.018	0.011	-9999	-10000	0	0
POU2F1	0.016	0.023	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.075	0.15	-9999	-0.51	41	41
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.011	0.006	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.003	0.04	-9999	-0.63	2	2
VLDLR	0.001	0.085	-9999	-0.57	11	11
CRKL	0.012	0.037	-9999	-0.82	1	1
LRPAP1	0.014	0	-9999	-10000	0	0
FYN	0.012	0.037	-9999	-0.82	1	1
ITGA3	-0.016	0.15	-9999	-0.8	18	18
RELN/VLDLR/Fyn	-0.078	0.15	-9999	-0.6	4	4
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.007	0.049	-9999	-0.46	3	3
AKT1	-0.032	0.12	-9999	-0.5	6	6
MAP2K7	0.014	0	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0
DAB1	-0.018	0.15	-9999	-0.82	16	16
RELN/LRP8/DAB1	-0.09	0.17	-9999	-0.57	27	27
LRPAP1/LRP8	-0.013	0.088	-9999	-0.63	10	10
RELN/LRP8/DAB1/Fyn	-0.084	0.16	-9999	-0.53	28	28
DAB1/alpha3/beta1 Integrin	-0.093	0.16	-9999	-0.66	10	10
long-term memory	-0.16	0.21	-9999	-0.56	65	65
DAB1/LIS1	-0.082	0.15	-9999	-0.67	9	9
DAB1/CRLK/C3G	-0.078	0.15	-9999	-0.66	10	10
PIK3CA	0.014	0	-9999	-10000	0	0
DAB1/NCK2	-0.082	0.15	-9999	-0.68	9	9
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.13	0.29	-9999	-0.67	106	106
CDK5R1	0.01	0.053	-9999	-0.82	2	2
RELN	-0.11	0.24	-9999	-0.57	102	102
PIK3R1	0.01	0.045	-9999	-0.57	3	3
RELN/LRP8/Fyn	-0.081	0.16	-9999	-0.62	12	12
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.16	0.22	-9999	-0.55	84	84
MAPK8	0.006	0.068	-9999	-0.57	7	7
RELN/VLDLR/DAB1	-0.087	0.16	-9999	-0.58	19	19
ITGB1	0.012	0.037	-9999	-0.82	1	1
MAP1B	-0.068	0.19	-9999	-0.6	27	27
RELN/LRP8	-0.08	0.16	-9999	-0.63	11	11
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.088	0.16	-9999	-0.53	32	32
PI3K	-0.002	0.031	-9999	-0.41	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.024	0.12	-9999	-0.62	19	19
RAP1A	-0.029	0.16	-9999	-0.64	8	8
PAFAH1B1	0.014	0	-9999	-10000	0	0
MAPK8IP1	0.008	0.069	-9999	-0.76	4	4
CRLK/C3G	-0.001	0.028	-9999	-0.63	1	1
GRIN2B	-0.004	0.082	-9999	-0.82	5	5
NCK2	0.014	0	-9999	-10000	0	0
neuron differentiation	-0.013	0.1	-9999	-0.4	8	8
neuron adhesion	-0.029	0.17	-9999	-0.6	9	9
LRP8	-0.003	0.12	-9999	-0.82	10	10
GSK3B	-0.023	0.12	-9999	-0.47	6	6
RELN/VLDLR/DAB1/Fyn	-0.081	0.15	-9999	-0.54	20	20
MAP3K11	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.044	0.13	-9999	-0.54	6	6
CDK5	0.014	0	-9999	-10000	0	0
MAPT	-0.23	0.27	-9999	-0.52	221	221
neuron migration	-0.024	0.17	-9999	-0.54	10	10
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.013	0.1	-9999	-0.4	8	8
RELN/VLDLR	-0.078	0.15	-9999	-0.58	13	13

×

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	-0.022	0.093	-9999	-0.39	28	28
EFNA5	-0.012	0.12	-9999	-0.57	22	22
FYN	0.001	0.096	-9999	-0.58	6	6
neuron projection morphogenesis	-0.022	0.093	-9999	-0.39	28	28
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.022	0.093	-9999	-0.39	28	28
EPHA5	-0.002	0.091	-9999	-0.82	6	6

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.11	0.29	-9999	-0.72	79	79
MKNK1	0.014	0	-9999	-10000	0	0
MAPK14	-0.046	0.13	-9999	-0.4	13	13
ATF2/c-Jun	-0.012	0.097	-9999	-10000	0	0
MAPK11	-0.046	0.13	-9999	-0.43	3	3
MITF	-0.053	0.17	-9999	-0.55	22	22
MAPKAPK5	-0.04	0.15	-9999	-0.49	13	13
KRT8	-0.12	0.23	-9999	-0.65	47	47
MAPKAPK3	0.014	0	-9999	-10000	0	0
MAPKAPK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.068	0.19	-9999	-0.65	13	13
CEBPB	-0.04	0.15	-9999	-0.49	13	13
SLC9A1	-0.04	0.15	-9999	-0.49	13	13
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.035	0.15	-9999	-0.48	13	13
p38alpha-beta/MNK1	-0.04	0.15	-9999	-0.53	13	13
JUN	-0.012	0.096	-9999	-10000	0	0
PPARGC1A	-0.18	0.26	-9999	-0.69	68	68
USF1	-0.04	0.15	-9999	-0.49	13	13
RAB5/GDP/GDI1	-0.053	0.087	-9999	-0.4	3	3
NOS2	-0.12	0.31	-9999	-0.75	86	86
DDIT3	-0.049	0.16	-9999	-0.52	17	17
RAB5A	0.014	0	-9999	-10000	0	0
HSPB1	-0.022	0.12	-9999	-0.44	3	3
p38alpha-beta/HBP1	-0.04	0.15	-9999	-0.53	13	13
CREB1	-0.037	0.15	-9999	-0.48	13	13
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.028	0.13	-9999	-0.47	13	13
RPS6KA4	-0.04	0.15	-9999	-0.49	13	13
PLA2G4A	-0.049	0.16	-9999	-0.62	9	9
GDI1	-0.04	0.15	-9999	-0.49	13	13
TP53	-0.057	0.18	-9999	-0.62	15	15
RPS6KA5	-0.043	0.15	-9999	-0.49	13	13
ESR1	-0.065	0.18	-9999	-0.57	27	27
HBP1	0.014	0	-9999	-10000	0	0
MEF2C	-0.048	0.15	-9999	-0.5	14	14
MEF2A	-0.04	0.15	-9999	-0.49	13	13
EIF4EBP1	-0.039	0.15	-9999	-0.48	13	13
KRT19	-0.18	0.22	-9999	-0.66	47	47
ELK4	-0.04	0.15	-9999	-0.49	13	13
ATF6	-0.04	0.15	-9999	-0.49	13	13
ATF1	-0.037	0.15	-9999	-0.48	13	13
p38alpha-beta/MAPKAPK2	-0.04	0.15	-9999	-0.53	13	13
p38alpha-beta/MAPKAPK3	-0.04	0.15	-9999	-0.53	13	13

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.037	-9999	-0.82	1	1
EGFR	-0.017	0.15	-9999	-0.76	20	20
EGF/EGFR	-0.073	0.14	-9999	-0.49	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.067	0.13	-9999	-0.49	19	19
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.006	0.074	-9999	-0.72	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.094	0.23	-9999	-0.57	91	91
EGF/EGFR dimer/SHC	-0.082	0.16	-9999	-0.57	19	19
mol:GDP	-0.067	0.13	-9999	-0.48	19	19
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.008	0.058	-9999	-0.57	5	5
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.061	0.12	-9999	-0.54	4	4
SHC1	0.014	0	-9999	-10000	0	0
HRAS/GDP	-0.063	0.12	-9999	-0.55	4	4
FRAP1	-0.033	0.14	-9999	-0.46	19	19
EGF/EGFR dimer	-0.098	0.19	-9999	-0.45	108	108
SOS1	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.01	0.068	-9999	-0.47	10	10

×

ErbB2/ErbB3 signaling events

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
USP8	0.02	0.005	-9999	-10000	0	0
RAS family/GTP	-0.021	0.11	-9999	-0.46	4	4
NFATC4	-0.017	0.12	-9999	-0.51	3	3
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.014	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.04	0.14	-9999	-0.59	1	1
JUN	0.005	0.085	-9999	-0.38	6	6
HRAS	0.011	0.037	-9999	-0.82	1	1
DOCK7	-0.032	0.14	-9999	-0.56	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.082	0.18	-9999	-0.48	79	79
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.04	0.075	-9999	-0.31	8	8
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.042	0.16	-9999	-0.66	1	1
RAF1	-0.018	0.12	-9999	-0.5	2	2
ErbB2/ErbB3/neuregulin 2	-0.19	0.16	-9999	-0.61	6	6
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.006	0.085	-9999	-0.27	1	1
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.14	0.29	-9999	-0.58	105	105
FOS	-0.1	0.23	-9999	-0.47	81	81
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.04	0.14	-9999	-0.59	1	1
MAPK3	-0.1	0.23	-9999	-0.58	19	19
MAPK1	-0.1	0.23	-9999	-0.58	19	19
JAK2	-0.032	0.14	-9999	-0.56	1	1
NF2	-0.002	0.005	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.027	0.12	-9999	-0.31	27	27
NRG1	-0.12	0.3	-9999	-0.8	81	81
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.016	0.11	-9999	-0.44	2	2
MAPK9	-0.029	0.063	-9999	-10000	0	0
ERBB2	-0.004	0.05	-9999	-0.64	3	3
ERBB3	0.004	0.068	-9999	-0.57	7	7
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
apoptosis	0.008	0.01	-9999	-10000	0	0
STAT3 (dimer)	0.009	0.01	-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	-0.041	0.089	-9999	-0.37	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.003	0.043	-9999	-0.55	3	3
CHRNA1	-0.15	0.3	-9999	-0.56	161	161
myelination	-0.007	0.12	-9999	-0.45	3	3
PPP3CB	-0.029	0.13	-9999	-0.51	1	1
KRAS	0.01	0.053	-9999	-0.82	2	2
RAC1-CDC42/GDP	-0.008	0.11	-9999	-0.59	1	1
NRG2	-0.32	0.28	-9999	-0.57	287	287
mol:GDP	-0.026	0.12	-9999	-0.31	27	27
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.023	0.13	-9999	-0.48	2	2
SRC	0.014	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.032	0.14	-9999	-0.56	1	1
MAP2K1	-0.089	0.2	-9999	-0.51	20	20
heart morphogenesis	-0.04	0.14	-9999	-0.59	1	1
RAS family/GDP	-0.016	0.11	-9999	-0.47	4	4
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.009	-9999	-10000	0	0
CHRNE	0.011	0.032	-9999	-0.23	6	6
HSP90AA1	0.014	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.04	0.14	-9999	-0.59	1	1
CDC42	0.014	0	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.005	0.041	-9999	-0.35	7	7
ARNO/beta Arrestin1-2	-0.018	0.066	-9999	-0.5	1	1
EGFR	-0.017	0.15	-9999	-0.76	20	20
EPHA2	0.004	0.073	-9999	-0.57	8	8
USP6	0.012	0.037	-9999	-0.82	1	1
IQSEC1	0.014	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.098	0.19	-9999	-0.45	108	108
ARRB2	0.01	0.003	-9999	-10000	0	0
mol:GTP	0.019	0.02	-9999	-0.16	1	1
ARRB1	0.011	0.037	-9999	-0.57	2	2
FBXO8	0.014	0	-9999	-10000	0	0
TSHR	-0.014	0.14	-9999	-0.82	15	15
EGF	-0.094	0.23	-9999	-0.57	91	91
somatostatin receptor activity	0	0	-9999	-0.001	12	12
ARAP2	0.007	0.063	-9999	-0.57	6	6
mol:GDP	-0.011	0.077	-9999	-0.32	11	11
mol:PI-3-4-5-P3	0	0	-9999	-0.001	7	7
ITGA2B	-0.065	0.24	-9999	-0.82	47	47
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.043	-9999	-0.49	1	1
ADAP1	0.013	0.026	-9999	-0.57	1	1
KIF13B	0.007	0.063	-9999	-0.57	6	6
HGF/MET	-0.025	0.11	-9999	-0.48	26	26
PXN	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.023	0.1	-9999	-0.32	13	13
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.082	0.16	-9999	-0.57	19	19
ADRB2	-0.027	0.15	-9999	-0.57	35	35
receptor agonist activity	0	0	-9999	0	12	12
actin filament binding	0	0	-9999	-0.001	12	12
SRC	0.014	0	-9999	-10000	0	0
ITGB3	-0.015	0.14	-9999	-0.73	19	19
GNAQ	0.014	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	8	8
ARF6/GDP	0.041	0.067	-9999	-0.39	2	2
ARF6/GDP/GULP/ACAP1	-0.1	0.15	-9999	-0.5	26	26
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.063	0.17	-9999	-0.52	57	57
ACAP1	-0.006	0.13	-9999	-0.82	12	12
ACAP2	0.014	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0.002	0.006	-9999	-10000	0	0
EFNA1	0.012	0.037	-9999	-0.82	1	1
HGF	-0.012	0.13	-9999	-0.63	20	20
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	9	9
endosomal lumen acidification	0	0	-9999	-0.001	10	10
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.16	0.26	-9999	-0.57	146	146
GNAQ/ARNO	0.015	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	1	1
MET	0.005	0.083	-9999	-0.74	6	6
GNA14	-0.075	0.21	-9999	-0.57	76	76
GNA15	0.011	0.037	-9999	-0.57	2	2
GIT1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	9	9
GNA11	0.009	0.052	-9999	-0.57	4	4
LHCGR	0.002	0.005	-9999	-10000	0	0
AGTR1	-0.043	0.17	-9999	-0.58	46	46
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.006	-9999	-10000	0	0
IPCEF1/ARNO	-0.046	0.14	-9999	-0.48	9	9
alphaIIb/beta3 Integrin	-0.08	0.21	-9999	-0.63	63	63

×

EPO 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
BCL2L1	0.024	0.13	-10000	0	-0.55	3	3
CRKL	-0.007	0.15	-10000	0	-0.57	3	3
mol:DAG	0.005	0.14	-10000	0	-0.62	3	3
HRAS	0.023	0.13	-10000	0	-0.6	2	2
MAPK8	-0.031	0.18	-10000	0	-0.48	65	65
RAP1A	-0.006	0.15	-10000	0	-0.64	2	2
GAB1	-0.006	0.15	-10000	0	-0.64	2	2
MAPK14	-0.026	0.18	-10000	0	-0.47	65	65
EPO	-0.077	0.26	-10000	0	-0.81	55	55
PLCG1	0.004	0.14	-10000	0	-0.64	3	3
EPOR/TRPC2/IP3 Receptors	-0.006	0.12	-10000	0	-0.81	11	11
RAPGEF1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.067	0.18	-10000	0	-0.52	65	65
GAB1/SHC/GRB2/SOS1	-0.044	0.11	-10000	0	-0.68	1	1
EPO/EPOR (dimer)	-0.06	0.22	-10000	0	-0.63	65	65
IRS2	-0.007	0.15	-10000	0	-0.64	2	2
STAT1	-0.01	0.17	-10000	0	-0.66	5	5
STAT5B	0.009	0.14	-10000	0	-0.65	3	3
cell proliferation	-0.02	0.17	-10000	0	-0.44	65	65
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.044	0.11	-10000	0	-0.59	4	4
TEC	-0.02	0.17	-10000	0	-0.69	9	9
SOCS3	0.013	0.026	-10000	0	-0.57	1	1
STAT1 (dimer)	-0.008	0.16	-10000	0	-0.64	5	5
JAK2	0.01	0.029	-10000	0	-0.56	1	1
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
EPO/EPOR (dimer)/JAK2	-0.003	0.16	-10000	0	-0.41	66	66
EPO/EPOR	-0.06	0.22	-10000	0	-0.63	65	65
LYN	0.014	0.037	-10000	0	-0.82	1	1
TEC/VAV2	-0.024	0.19	-10000	0	-0.75	12	12
elevation of cytosolic calcium ion concentration	-0.006	0.12	-10000	0	-0.81	11	11
SHC1	0.014	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.034	0.19	-10000	0	-0.53	65	65
mol:IP3	0.005	0.14	-10000	0	-0.62	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.05	0.12	-10000	0	-0.66	4	4
SH2B3	0.009	0.039	-10000	0	-0.81	1	1
NFKB1	-0.026	0.18	-10000	0	-0.47	65	65
EPO/EPOR (dimer)/JAK2/SOCS3	-0.036	0.096	0.28	1	-0.39	2	3
PTPN6	-0.015	0.16	-10000	0	-0.41	66	66
TEC/VAV2/GRB2	-0.017	0.18	-10000	0	-0.72	12	12
EPOR	-0.006	0.12	-10000	0	-0.82	11	11
INPP5D	0.01	0.045	-10000	0	-0.57	3	3
mol:GDP	-0.045	0.11	-10000	0	-0.7	1	1
SOS1	0.014	0	-10000	0	-10000	0	0
PLCG2	0.013	0.026	-10000	0	-0.57	1	1
CRKL/CBL/C3G	0.009	0.14	-10000	0	-0.73	1	1
VAV2	-0.02	0.18	-10000	0	-0.55	17	17
CBL	-0.006	0.15	-10000	0	-0.64	2	2
SHC/Grb2/SOS1	-0.047	0.12	-10000	0	-0.73	1	1
STAT5A	0.009	0.14	-10000	0	-0.65	3	3
GRB2	0.014	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.027	0.15	-10000	0	-0.68	3	3
LYN/PLCgamma2	-0.002	0.033	-10000	0	-0.52	2	2
PTPN11	0.014	0	-10000	0	-10000	0	0
BTK	-0.008	0.15	-10000	0	-0.64	2	2
BCL2	0.017	0.16	-10000	0	-0.69	10	10

×

Signaling events mediated by HDAC Class III

Figure S63. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S63. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.011	0.037	-10000	0	-0.57	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	0.012	0.14	0.62	26	-10000	0	26
CDKN1A	0.001	0.012	-10000	0	-10000	0	0
KAT2B	-0.014	0.12	-10000	0	-0.57	24	24
BAX	0.014	0	-10000	0	-10000	0	0
FOXO3	0.002	0.028	0.44	2	-10000	0	2
FOXO1	0.014	0	-10000	0	-10000	0	0
FOXO4	0.022	0.028	-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	-0.002	0.091	-10000	0	-0.82	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.074	0.18	-10000	0	-0.43	102	102
PPARGC1A	-0.2	0.28	-10000	0	-0.57	179	179
FHL2	0.011	0.037	-10000	0	-0.57	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.018	-10000	0	-0.41	1	1
HIST2H4A	-0.012	0.14	-10000	0	-0.62	26	26
SIRT1/FOXO3a	0	0.024	0.29	2	-0.35	1	3
SIRT1	-0.001	0.025	-10000	0	-0.57	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.015	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.012	0.052	-10000	0	-0.33	1	1
apoptosis	0.001	0.015	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.13	0.17	-10000	0	-0.35	179	179
p53/SIRT1	-0.004	0.041	-10000	0	-0.41	5	5
SIRT1/FOXO4	-0.002	0.026	-10000	0	-0.33	1	1
FOXO1/FHL2/SIRT1	-0.002	0.024	-10000	0	-10000	0	0
HIST1H1E	0.01	0.065	-10000	0	-0.29	23	23
SIRT1/p300	-0.002	0.031	-10000	0	-0.41	3	3
muscle cell differentiation	0.075	0.15	0.59	9	-10000	0	9
TP53	-0.005	0.051	-10000	0	-0.57	4	4
KU70/SIRT1/BAX	-0.001	0.015	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
MEF2D	0.014	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.008	0.071	-10000	0	-0.6	7	7
ACSS2	0.021	0.019	-10000	0	-0.41	1	1
SIRT1/PCAF/MYOD	-0.075	0.15	-10000	0	-0.6	9	9

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.001	0.11	-9999	-0.79	9	9
positive regulation of NF-kappaB transcription factor activity	-0.029	0.13	-9999	-0.6	24	24
MAP2K4	0.009	0.1	-9999	-0.48	1	1
IKBKB	0.014	0	-9999	-10000	0	0
TNFRSF10B	0.014	0	-9999	-10000	0	0
TNFRSF10A	0.011	0.037	-9999	-0.57	2	2
SMPD1	0.016	0.036	-9999	-0.26	8	8
IKBKG	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	-0.01	0.14	-9999	-0.78	15	15
TRAIL/TRAILR2	-0.011	0.081	-9999	-0.6	9	9
TRAIL/TRAILR3	-0.029	0.13	-9999	-0.6	24	24
TRAIL/TRAILR1	-0.013	0.085	-9999	-0.57	11	11
TRAIL/TRAILR4	-0.029	0.13	-9999	-0.6	24	24
TRAIL/TRAILR1/DAP3/GTP	-0.01	0.067	-9999	-0.5	8	8
IKK complex	-0.025	0.062	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.013	0.084	-9999	-0.6	9	9
MAP3K1	0.001	0.11	-9999	-0.51	1	1
TRAILR4 (trimer)	-0.01	0.14	-9999	-0.78	15	15
TRADD	0.014	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.011	0.037	-9999	-0.56	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.006	0.11	-9999	-0.54	1	1
CFLAR	0.014	0	-9999	-10000	0	0
MAPK1	0.013	0.084	-9999	-0.6	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.064	0.16	-9999	-0.46	67	67
mol:ceramide	0.016	0.036	-9999	-0.26	8	8
FADD	-0.085	0.27	-9999	-0.82	59	59
MAPK8	0.013	0.11	-9999	-0.48	4	4
TRAF2	0.002	0.098	-9999	-0.82	7	7
TRAILR3 (trimer)	-0.01	0.14	-9999	-0.78	15	15
CHUK	0.014	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.075	0.19	-9999	-0.54	67	67
DAP3	0.014	0	-9999	-10000	0	0
CASP10	-0.053	0.16	-9999	-0.44	64	64
JNK cascade	-0.029	0.13	-9999	-0.6	24	24
TRAIL (trimer)	-0.001	0.11	-9999	-0.79	9	9
TNFRSF10C	-0.01	0.14	-9999	-0.78	15	15
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.065	0.16	-9999	-0.47	67	67
TRAIL/TRAILR2/FADD	-0.074	0.19	-9999	-0.54	67	67
cell death	0.016	0.036	-9999	-0.26	8	8
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.005	0.11	-9999	-0.54	1	1
TRAILR2 (trimer)	0.014	0	-9999	-10000	0	0
CASP8	-0.001	0.022	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.063	0.16	-9999	-0.46	67	67

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.034	0.12	-10000	0	-0.48	27	27
ER alpha/Gai/GDP/Gbeta gamma	0.018	0.1	-10000	0	-0.45	5	5
AKT1	0.004	0.15	-10000	0	-0.75	15	15
PIK3CA	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.002	0.15	-10000	0	-0.76	15	15
mol:Ca2+	-0.03	0.16	-10000	0	-0.54	12	12
IGF1R	0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.043	0.13	-10000	0	-0.42	51	51
SHC1	0.014	0	-10000	0	-10000	0	0
apoptosis	-0.005	0.14	0.71	15	-10000	0	15
RhoA/GTP	-0.023	0.087	-10000	0	-0.41	19	19
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.028	0.09	-10000	0	-0.54	2	2
regulation of stress fiber formation	-0.03	0.087	0.5	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.04	0.14	-10000	0	-0.48	41	41
KRAS	0.01	0.053	-10000	0	-0.82	2	2
G13/GTP	-0.026	0.1	-10000	0	-0.41	31	31
pseudopodium formation	0.03	0.087	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/PELP1	-0.028	0.11	-10000	0	-0.45	31	31
GRB2	0.014	0	-10000	0	-10000	0	0
GNG2	0.012	0.037	-10000	0	-0.82	1	1
GNAO1	0.008	0.069	-10000	0	-0.76	4	4
HRAS	0.012	0.037	-10000	0	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.017	0.12	-10000	0	-0.47	16	16
E2/ER beta (dimer)	-0.014	0.091	-10000	0	-0.62	11	11
mol:GDP	-0.033	0.11	-10000	0	-0.38	41	41
mol:NADP	0.017	0.12	-10000	0	-0.47	16	16
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
mol:IP3	-0.033	0.16	-10000	0	-0.57	12	12
IGF-1R heterotetramer	0.014	0	-10000	0	-10000	0	0
PLCB1	-0.038	0.17	-10000	0	-0.4	77	77
PLCB2	-0.041	0.17	-10000	0	-0.4	80	80
IGF1	-0.088	0.22	-10000	0	-0.58	85	85
mol:L-citrulline	0.017	0.12	-10000	0	-0.47	16	16
RHOA	0.014	0	-10000	0	-10000	0	0
Gai/GDP	-0.014	0.061	-10000	0	-0.55	3	3
JNK cascade	-0.014	0.091	-10000	0	-0.62	11	11
BCAR1	0.014	0	-10000	0	-10000	0	0
ESR2	-0.004	0.12	-10000	0	-0.8	11	11
GNAQ	0.014	0	-10000	0	-10000	0	0
ESR1	-0.031	0.18	-10000	0	-0.7	31	31
Gq family/GDP/Gbeta gamma	-0.001	0.11	-10000	0	-0.61	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.026	0.067	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.028	0.09	-10000	0	-0.54	2	2
GNAZ	-0.017	0.15	-10000	0	-0.74	20	20
E2/ER alpha (dimer)	-0.033	0.13	-10000	0	-0.53	31	31
STRN	-0.012	0.12	-10000	0	-0.57	22	22
GNAL	-0.061	0.19	-10000	0	-0.57	64	64
PELP1	0.014	0	-10000	0	-10000	0	0
MAPK11	0.008	0.081	-10000	0	-0.53	11	11
GNAI2	0.014	0	-10000	0	-10000	0	0
GNAI3	0.014	0	-10000	0	-10000	0	0
GNAI1	0.013	0.026	-10000	0	-0.57	1	1
HBEGF	-0.17	0.17	-10000	0	-0.46	89	89
cAMP biosynthetic process	-0.067	0.14	-10000	0	-0.49	31	31
SRC	0.025	0.096	-10000	0	-0.51	2	2
PI3K	-0.002	0.031	-10000	0	-0.41	3	3
GNB1	0.014	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.03	0.096	-10000	0	-0.55	2	2
SOS1	0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.055	0.11	-10000	0	-0.5	9	9
Gs family/GTP	-0.069	0.15	-10000	0	-0.5	31	31
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.039	-10000	0	-0.5	3	3
vasodilation	0.018	0.11	-10000	0	-0.45	16	16
mol:DAG	-0.033	0.16	-10000	0	-0.57	12	12
Gs family/GDP/Gbeta gamma	-0.054	0.11	-10000	0	-0.55	8	8
MSN	0.03	0.093	-10000	0	-0.56	1	1
Gq family/GTP	-0.076	0.16	-10000	0	-0.42	77	77
mol:PI-3-4-5-P3	0.003	0.14	-10000	0	-0.73	15	15
NRAS	0.014	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.018	0.11	0.45	16	-10000	0	16
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.031	0.1	-10000	0	-0.36	40	40
NOS3	0.016	0.12	-10000	0	-0.49	16	16
GNA11	0.009	0.052	-10000	0	-0.57	4	4
MAPKKK cascade	0.016	0.14	-10000	0	-0.56	17	17
E2/ER alpha (dimer)/PELP1/Src	-0.03	0.095	-10000	0	-0.53	3	3
ruffle organization	0.03	0.087	-10000	0	-0.5	1	1
ROCK2	0.023	0.1	-10000	0	-0.63	1	1
GNA14	-0.075	0.21	-10000	0	-0.57	76	76
GNA15	0.011	0.037	-10000	0	-0.57	2	2
GNA13	0.014	0	-10000	0	-10000	0	0
MMP9	-0.3	0.21	-10000	0	-0.59	48	48
MMP2	-0.032	0.18	-10000	0	-0.58	6	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.014	0	-9999	-10000	0	0
VLDLR	0.001	0.085	-9999	-0.57	11	11
LRPAP1	0.014	0	-9999	-10000	0	0
NUDC	0.014	0	-9999	-10000	0	0
RELN/LRP8	-0.08	0.16	-9999	-0.63	11	11
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	-0.043	0.16	-9999	-0.57	11	11
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.018	0.15	-9999	-0.82	16	16
IQGAP1	0.014	0	-9999	-10000	0	0
PLA2G7	-0.31	0.41	-9999	-0.82	193	193
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	0.088	-9999	-0.63	10	10
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0.037	-9999	-0.57	2	2
CDK5R1	0.01	0.053	-9999	-0.82	2	2
LIS1/Poliovirus Protein 3A	0.018	0	-9999	-10000	0	0
CDK5R2	-0.1	0.29	-9999	-0.82	69	69
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.095	0.18	-9999	-0.62	19	19
YWHAE	0.014	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.042	0.16	-9999	-0.55	15	15
MAP1B	-0.007	0.045	-9999	-0.3	11	11
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.024	0.14	-9999	-0.7	4	4
RELN	-0.11	0.24	-9999	-0.57	102	102
PAFAH/LIS1	-0.19	0.28	-9999	-0.54	193	193
LIS1/CLIP170	0.027	0.023	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.062	0.098	-9999	-0.54	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.033	0.13	-9999	-0.56	7	7
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.053	0.17	-9999	-0.6	15	15
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	0.009	0.064	-9999	-0.82	3	3
PAFAH1B2	0.011	0.037	-9999	-0.57	2	2
MAP1B/LIS1/Dynein heavy chain	0.022	0.032	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.078	0.12	-9999	-0.61	7	7
LRP8	-0.003	0.12	-9999	-0.82	10	10
NDEL1/Katanin 60	-0.042	0.16	-9999	-0.64	7	7
P39/CDK5	-0.091	0.21	-9999	-0.79	14	14
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.031	0.15	-9999	-0.53	11	11
PPP2R5D	0.014	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.001	0.018	-9999	-10000	0	0
CSNK2A1	0.014	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.078	0.15	-9999	-0.53	19	19
RELN/VLDLR	-0.078	0.15	-9999	-0.58	13	13
CDC42	0	0	-9999	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.056	0.19	-9999	-0.57	59	59
GNB1/GNG2	-0.02	0.15	-9999	-0.63	12	12
mol:DAG	-0.009	0.14	-9999	-0.58	11	11
PLCG1	-0.01	0.14	-9999	-0.6	11	11
YES1	-0.027	0.15	-9999	-0.68	11	11
FZD3	0.006	0.068	-9999	-0.57	7	7
FZD6	0.011	0.045	-9999	-0.69	2	2
G protein	-0.01	0.14	-9999	-0.61	11	11
MAP3K7	-0.057	0.17	-9999	-0.65	8	8
mol:Ca2+	-0.008	0.13	-9999	-0.56	11	11
mol:IP3	-0.009	0.14	-9999	-0.58	11	11
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.07	0.18	-9999	-0.52	32	32
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.038	0.16	-9999	-0.73	11	11
CSNK1A1	0.014	0	-9999	-10000	0	0
GNAS	-0.027	0.15	-9999	-0.68	11	11
GO:0007205	-0.008	0.13	-9999	-0.56	11	11
WNT6	-0.052	0.22	-9999	-0.76	42	42
WNT4	-0.007	0.12	-9999	-0.63	16	16
NFAT1/CK1 alpha	-0.08	0.15	-9999	-0.57	25	25
GNG2	0.012	0.037	-9999	-0.82	1	1
WNT5A	0.005	0.073	-9999	-0.6	7	7
WNT11	-0.074	0.25	-9999	-0.75	57	57
CDC42	-0.017	0.14	-9999	-0.64	11	11

×

PDGFR-alpha signaling 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
PDGFRA	0	0.087	-9999	-0.62	9	9
PDGF/PDGFRA/CRKL	-0.009	0.067	-9999	-0.46	10	10
positive regulation of JUN kinase activity	-0.006	0.044	-9999	-0.46	2	2
CRKL	0.012	0.037	-9999	-0.82	1	1
PDGF/PDGFRA/Caveolin-3	-0.1	0.18	-9999	-0.43	116	116
AP1	-0.13	0.32	-9999	-0.94	64	64
mol:IP3	0.012	0.068	-9999	-0.46	9	9
PLCG1	0.012	0.069	-9999	-0.46	9	9
PDGF/PDGFRA/alphaV Integrin	-0.014	0.088	-9999	-0.53	13	13
RAPGEF1	0.014	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.068	-9999	-0.46	9	9
CAV3	-0.12	0.24	-9999	-0.57	109	109
CAV1	-0.05	0.22	-9999	-0.82	38	38
SHC/Grb2/SOS1	-0.006	0.045	-9999	-0.47	2	2
PDGF/PDGFRA/Shf	-0.015	0.087	-9999	-0.48	16	16
FOS	-0.082	0.33	-9999	-0.93	64	64
JUN	-0.008	0.02	-9999	-10000	0	0
oligodendrocyte development	-0.014	0.088	-9999	-0.53	13	13
GRB2	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
mol:DAG	0.012	0.068	-9999	-0.46	9	9
PDGF/PDGFRA	0	0.087	-9999	-0.62	9	9
actin cytoskeleton reorganization	-0.01	0.065	-9999	-0.44	11	11
SRF	0.025	0.009	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
PI3K	-0.009	0.056	-9999	-0.52	2	2
PDGF/PDGFRA/Crk/C3G	-0.007	0.05	-9999	-0.52	2	2
JAK1	0.015	0.064	-9999	-0.44	9	9
ELK1/SRF	0.033	0.055	-9999	-0.5	1	1
SHB	0.011	0.037	-9999	-0.57	2	2
SHF	0.003	0.077	-9999	-0.57	9	9
CSNK2A1	0.008	0.02	-9999	-10000	0	0
GO:0007205	0.012	0.07	-9999	-0.47	9	9
SOS1	0.014	0	-9999	-10000	0	0
Ras protein signal transduction	-0.006	0.044	-9999	-0.46	2	2
PDGF/PDGFRA/SHB	-0.01	0.066	-9999	-0.44	11	11
PDGF/PDGFRA/Caveolin-1	-0.057	0.18	-9999	-0.6	47	47
ITGAV	0.006	0.079	-9999	-0.77	5	5
ELK1	0.015	0.073	-9999	-0.53	4	4
PIK3CA	0.014	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.008	0.06	-9999	-0.44	9	9
JAK-STAT cascade	0.015	0.064	-9999	-0.44	9	9
cell proliferation	-0.015	0.086	-9999	-0.47	16	16

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.032	0.042	-9999	-0.58	2	2
VEGFR1 homodimer/NRP1	0.022	0.034	-9999	-0.63	1	1
mol:DAG	-0.056	0.21	-9999	-0.48	93	93
VEGFR1 homodimer/NRP1/VEGFR 121	-0.008	0.061	-9999	-0.51	7	7
CaM/Ca2+	-0.046	0.2	-9999	-0.63	2	2
HIF1A	0.02	0.03	-9999	-0.55	1	1
GAB1	0.014	0	-9999	-10000	0	0
AKT1	-0.021	0.18	-9999	-0.73	4	4
PLCG1	-0.056	0.21	-9999	-0.49	93	93
NOS3	-0.018	0.18	-9999	-0.55	5	5
CBL	0.014	0	-9999	-10000	0	0
mol:NO	-0.016	0.17	-9999	-0.53	5	5
FLT1	0.031	0.039	-9999	-0.72	1	1
PGF	-0.14	0.32	-9999	-0.82	92	92
VEGFR1 homodimer/NRP2/VEGFR121	-0.01	0.068	-9999	-0.5	9	9
CALM1	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
eNOS/Hsp90	-0.009	0.17	-9999	-0.62	2	2
endothelial cell proliferation	-0.032	0.18	-9999	-0.71	1	1
mol:Ca2+	-0.055	0.2	-9999	-0.48	93	93
MAPK3	-0.035	0.18	-9999	-0.66	1	1
MAPK1	-0.035	0.18	-9999	-0.66	1	1
PIK3R1	0.01	0.045	-9999	-0.57	3	3
PLGF homodimer	-0.14	0.32	-9999	-0.82	92	92
PRKACA	0.014	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.05	0.22	-9999	-0.82	38	38
VEGFA homodimer	0.004	0.091	-9999	-0.82	6	6
VEGFR1 homodimer/VEGFA homodimer	0.026	0.071	-9999	-0.55	7	7
platelet activating factor biosynthetic process	-0.026	0.18	-9999	-0.64	1	1
PI3K	-0.087	0.18	-9999	-0.7	5	5
PRKCA	-0.045	0.19	-9999	-0.61	2	2
PRKCB	-0.051	0.2	-9999	-0.61	2	2
VEGFR1 homodimer/PLGF homodimer	-0.073	0.22	-9999	-0.54	93	93
VEGFA	0.004	0.091	-9999	-0.82	6	6
VEGFB	0.012	0.037	-9999	-0.82	1	1
mol:IP3	-0.056	0.21	-9999	-0.48	93	93
RASA1	0.039	0.048	-9999	-0.55	3	3
NRP2	0.01	0.053	-9999	-0.82	2	2
VEGFR1 homodimer	0.031	0.039	-9999	-0.72	1	1
VEGFB homodimer	0.012	0.037	-9999	-0.82	1	1
NCK1	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.043	0.2	-9999	-0.72	10	10
PTPN11	0.014	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.086	0.18	-9999	-0.69	5	5
mol:L-citrulline	-0.016	0.17	-9999	-0.53	5	5
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.007	0.056	-9999	-0.54	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.008	0.06	-9999	-0.5	7	7
CD2AP	0.014	0	-9999	-10000	0	0
PI3K/GAB1	-0.082	0.17	-9999	-0.66	5	5
PDPK1	-0.037	0.19	-9999	-0.7	5	5
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.008	0.06	-9999	-0.5	7	7
mol:NADP	-0.016	0.17	-9999	-0.53	5	5
HSP90AA1	0.014	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.007	0.056	-9999	-0.53	1	1
VEGFR1 homodimer/NRP2	0.03	0.049	-9999	-0.57	3	3

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.012	0.037	-9999	-0.82	1	1
LAT2	-0.053	0.14	-9999	-0.48	20	20
AP1	-0.089	0.12	-9999	-0.53	12	12
mol:PIP3	-0.069	0.19	-9999	-0.55	26	26
IKBKB	-0.025	0.11	-9999	-0.35	5	5
AKT1	-0.052	0.16	-9999	-0.64	6	6
IKBKG	-0.025	0.11	-9999	-0.35	5	5
MS4A2	-0.012	0.12	-9999	-0.58	20	20
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
MAP3K1	-0.017	0.12	-9999	-0.48	5	5
mol:Ca2+	-0.049	0.15	-9999	-0.4	26	26
LYN	0.012	0.038	-9999	-0.83	1	1
CBLB	-0.05	0.14	-9999	-0.48	19	19
SHC1	0.014	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.018	0.073	-9999	-0.5	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.01	0.045	-9999	-0.57	3	3
PLD2	-0.088	0.18	-9999	-0.56	25	25
PTPN13	-0.047	0.14	-9999	-0.48	21	21
PTPN11	0.01	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.021	0.13	-9999	-0.4	4	4
SYK	0.01	0.046	-9999	-0.58	3	3
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.16	-9999	-0.57	28	28
LAT	-0.065	0.16	-9999	-0.53	32	32
PAK2	-0.028	0.13	-9999	-0.52	6	6
NFATC2	-0.12	0.22	-9999	-0.69	59	59
HRAS	-0.038	0.14	-9999	-0.45	24	24
GAB2	0.01	0.045	-9999	-0.57	3	3
PLA2G1B	0.035	0.019	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.2	-9999	-0.65	27	27
Antigen/IgE/Fc epsilon R1	-0.14	0.19	-9999	-0.6	27	27
mol:GDP	-0.045	0.14	-9999	-0.47	24	24
JUN	0.014	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
FOS	-0.061	0.19	-9999	-0.57	64	64
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.086	0.13	-9999	-0.5	20	20
CHUK	-0.025	0.11	-9999	-0.35	5	5
KLRG1	-0.058	0.14	-9999	-0.47	24	24
VAV1	-0.057	0.14	-9999	-0.48	24	24
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.05	0.14	-9999	-0.48	19	19
negative regulation of mast cell degranulation	-0.048	0.14	-9999	-0.53	9	9
BTK	-0.049	0.14	-9999	-0.48	19	19
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.084	0.18	-9999	-0.62	24	24
GAB2/PI3K/SHP2	-0.1	0.14	-9999	-0.65	9	9
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.07	0.16	-9999	-0.58	19	19
RAF1	0.023	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.17	-9999	-0.61	23	23
FCER1G	-0.008	0.13	-9999	-0.82	12	12
FCER1A	-0.19	0.28	-9999	-0.57	176	176
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.18	-9999	-0.6	25	25
MAPK3	0.034	0.019	-9999	-10000	0	0
MAPK1	0.034	0.019	-9999	-10000	0	0
NFKB1	0.014	0	-9999	-10000	0	0
MAPK8	0.001	0.09	-9999	-0.66	7	7
DUSP1	-0.015	0.13	-9999	-0.57	25	25
NF-kappa-B/RelA	-0.036	0.047	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.05	0.14	-9999	-0.47	19	19
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.071	0.11	-9999	-0.59	5	5
FER	-0.052	0.14	-9999	-0.48	21	21
RELA	0.014	0	-9999	-10000	0	0
ITK	-0.032	0.078	-9999	-0.41	17	17
SOS1	0.014	0	-9999	-10000	0	0
PLCG1	-0.044	0.15	-9999	-0.48	24	24
cytokine secretion	-0.027	0.035	-9999	-10000	0	0
SPHK1	-0.062	0.16	-9999	-0.53	30	30
PTK2	-0.052	0.14	-9999	-0.49	19	19
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.16	-9999	-0.57	21	21
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.06	0.18	-9999	-0.53	20	20
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	-0.081	0.12	-9999	-0.5	13	13
MAP2K4	0.019	0.009	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.14	0.19	-9999	-0.61	30	30
mol:Choline	-0.086	0.18	-9999	-0.55	25	25
SHC/Grb2/SOS1	-0.069	0.11	-9999	-0.66	3	3
FYN	0.012	0.037	-9999	-0.82	1	1
DOK1	0.012	0.037	-9999	-0.82	1	1
PXN	-0.041	0.13	-9999	-0.47	15	15
HCLS1	-0.055	0.14	-9999	-0.48	24	24
PRKCB	-0.047	0.15	-9999	-0.4	22	22
FCGR2B	0.006	0.068	-9999	-0.57	7	7
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.049	0.14	-9999	-0.55	9	9
LCP2	0.008	0.065	-9999	-0.82	3	3
PLA2G4A	-0.069	0.16	-9999	-0.52	35	35
RASA1	0.011	0.037	-9999	-0.57	2	2
mol:Phosphatidic acid	-0.086	0.18	-9999	-0.55	25	25
IKK complex	-0.003	0.091	-9999	-0.28	2	2
WIPF1	0.007	0.074	-9999	-0.82	4	4

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.02	0.08	-9999	-0.47	12	12
CRKL	0.012	0.037	-9999	-0.82	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.011	0.037	-9999	-0.57	2	2
ITGA4	-0.005	0.12	-9999	-0.82	11	11
alpha4/beta7 Integrin/MAdCAM1	-0.028	0.11	-9999	-0.49	27	27
EPO	-0.08	0.26	-9999	-0.82	55	55
alpha4/beta7 Integrin	-0.016	0.096	-9999	-0.59	13	13
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.015	0.096	-9999	-0.63	12	12
EPO/EPOR (dimer)	-0.083	0.22	-9999	-0.64	65	65
lamellipodium assembly	0	0.027	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.031	-9999	-0.41	3	3
ARF6	0.014	0	-9999	-10000	0	0
JAK2	-0.018	0.13	-9999	-0.52	4	4
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
MADCAM1	-0.017	0.15	-9999	-0.82	16	16
cell adhesion	-0.028	0.11	-9999	-0.49	27	27
CRKL/CBL	-0.001	0.028	-9999	-0.63	1	1
ITGB1	0.012	0.037	-9999	-0.82	1	1
SRC	-0.027	0.17	-9999	-0.51	52	52
ITGB7	0.011	0.037	-9999	-0.57	2	2
RAC1	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.065	0.18	-9999	-0.56	52	52
p130Cas/Crk/Dock1	-0.001	0.15	-9999	-0.81	2	2
VCAM1	-0.067	0.24	-9999	-0.77	51	51
RHOA	0.014	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.012	0.076	-9999	-0.49	12	12
BCAR1	-0.016	0.16	-9999	-0.47	52	52
EPOR	-0.005	0.12	-9999	-0.82	11	11
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
Rac1/GTP	0	0.028	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.077	-9999	-0.61	8	8
PDGFRB	-0.14	0.32	-9999	-0.82	89	89
SPHK1	-0.023	0.052	-9999	-0.32	12	12
mol:S1P	-0.028	0.062	-9999	-0.42	6	6
S1P1/S1P/Gi	-0.015	0.14	-9999	-0.51	11	11
GNAO1	0.006	0.07	-9999	-0.76	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.066	0.2	-9999	-0.62	17	17
PLCG1	-0.015	0.13	-9999	-0.52	8	8
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.14	0.32	-9999	-0.82	89	89
GNAI2	0.012	0.006	-9999	-10000	0	0
GNAI3	0.012	0.006	-9999	-10000	0	0
GNAI1	0.011	0.027	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.009	0.07	-9999	-0.53	8	8
S1P1/S1P	-0.039	0.079	-9999	-0.44	11	11
negative regulation of cAMP metabolic process	-0.015	0.13	-9999	-0.5	11	11
MAPK3	-0.023	0.17	-9999	-0.56	15	15
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	0.01	0.045	-9999	-0.69	2	2
PLCB2	-0.002	0.096	-9999	-0.44	10	10
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.032	0.066	-9999	-0.4	7	7
receptor internalization	-0.037	0.074	-9999	-0.41	12	12
PTGS2	-0.052	0.25	-9999	-0.6	79	79
Rac1/GTP	-0.032	0.066	-9999	-0.4	7	7
RHOA	0.014	0	-9999	-10000	0	0
VEGFA	0.003	0.092	-9999	-0.82	6	6
negative regulation of T cell proliferation	-0.015	0.13	-9999	-0.5	11	11
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.019	0.15	-9999	-0.75	20	20
MAPK1	-0.023	0.17	-9999	-0.56	15	15
S1P1/S1P/PDGFB-D/PDGFRB	-0.059	0.18	-9999	-0.57	18	18
ABCC1	0.008	0.065	-9999	-0.82	3	3

×

Signaling events mediated by PRL

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
CCNE1	0.002	0.098	-10000	0	-0.82	7	7
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	-0.11	0.29	-10000	0	-0.82	72	72
CDKN1A	0.029	0.032	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.01	0.079	-10000	0	-0.63	8	8
mol:Ca2+	-0.079	0.18	0.38	6	-0.43	97	103
AGT	-0.1	0.24	-10000	0	-0.58	97	97
CCNA2	0.03	0.073	-10000	0	-0.74	1	1
TUBA1B	0.014	0	-10000	0	-10000	0	0
EGR1	0.006	0.091	-10000	0	-0.4	24	24
CDK2/Cyclin E1	0.034	0.063	-10000	0	-0.44	7	7
MAPK3	0.014	0.082	-10000	0	-0.63	8	8
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.082	-10000	0	-0.63	8	8
PTP4A1	0.024	0.071	-10000	0	-10000	0	0
PTP4A3	0	0.1	-10000	0	-0.82	8	8
PTP4A2	0.014	0	-10000	0	-10000	0	0
ITGB1	0.013	0.087	-10000	0	-0.63	9	9
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.025	0.046	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.018	0.1	-10000	0	-0.74	1	1
RABGGTA	0.014	0	-10000	0	-10000	0	0
BCAR1	0.006	0.047	0.38	8	-10000	0	8
RHOC	0.025	0.046	-10000	0	-10000	0	0
RHOA	0.025	0.046	-10000	0	-10000	0	0
cell motility	0.029	0.048	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.029	0.066	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.1	0.23	-10000	0	-0.63	80	80
ROCK1	0.029	0.048	-10000	0	-10000	0	0
RABGGTB	0.014	0	-10000	0	-10000	0	0
CDK2	0.014	0	-10000	0	-10000	0	0
mitosis	0.024	0.07	-10000	0	-10000	0	0
ATF5	-0.005	0.12	-10000	0	-0.82	11	11

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.009	0.064	-10000	0	-0.82	3	3
ANTXR2	-0.005	0.12	-10000	0	-0.82	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.016	-10000	0	-0.098	14	14
monocyte activation	-0.027	0.12	-10000	0	-0.29	71	71
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.014	-10000	0	-10000	0	0
MAP2K7	-0.002	0.014	-10000	0	-10000	0	0
MAP2K6	-0.018	0.069	-10000	0	-0.3	26	26
CYAA	0.002	0.082	-10000	0	-0.48	14	14
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.035	0.15	-10000	0	-0.46	53	53
Channel	-0.014	0.084	-10000	0	-0.51	14	14
NLRP1	-0.003	0.026	-10000	0	-0.49	1	1
CALM1	0.014	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.016	0.098	14	-10000	0	14
MAPK3	-0.002	0.014	-10000	0	-10000	0	0
MAPK1	-0.002	0.014	-10000	0	-10000	0	0
PGR	-0.043	0.11	-10000	0	-0.33	60	60
PA/Cellular Receptors	-0.016	0.091	-10000	0	-0.55	14	14
apoptosis	-0.003	0.016	-10000	0	-0.098	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.079	-10000	0	-0.46	14	14
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.025	0.17	-10000	0	-0.79	24	24
VCAM1	-0.027	0.12	-10000	0	-0.29	71	71
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.025	0.16	1	-10000	0	1
IL18	0.005	0.062	-10000	0	-0.29	20	20
negative regulation of macrophage activation	-0.003	0.016	-10000	0	-0.098	14	14
LEF	-0.003	0.016	-10000	0	-0.099	14	14
CASP1	-0.003	0.017	-10000	0	-0.22	1	1
mol:cAMP	-0.003	0.02	-10000	0	-10000	0	0
necrosis	-0.003	0.016	-10000	0	-0.098	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.003	0.083	-10000	0	-0.48	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0	-10000	0	-10000	0	0
HDAC3	0.014	0	-10000	0	-10000	0	0
VDR	0.011	0.037	-10000	0	-0.57	2	2
Cbp/p300/PCAF	-0.018	0.078	-10000	0	-0.66	1	1
EP300	0.011	0.037	-10000	0	-0.57	2	2
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.008	0.099	-10000	0	-0.48	9	9
KAT2B	-0.014	0.12	-10000	0	-0.57	24	24
MAPK14	0.014	0	-10000	0	-10000	0	0
AKT1	0.031	0.11	0.22	2	-0.35	5	7
RAR alpha/9cRA/Cyclin H	-0.023	0.06	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.002	0.11	-10000	0	-0.44	13	13
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	-0.022	0.081	-10000	0	-0.46	7	7
NCOR2	0.014	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-10000	0	-0.42	2	2
RXRs/RARs/NRIP1/9cRA	0.001	0.14	-10000	0	-0.6	6	6
NCOA2	-0.031	0.15	-10000	0	-0.57	38	38
NCOA3	0.014	0	-10000	0	-10000	0	0
NCOA1	0.014	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.037	-10000	0	-0.56	2	2
RARG	0.014	0.026	-10000	0	-0.57	1	1
RAR gamma1/9cRA	-0.001	0.015	-10000	0	-0.35	1	1
MAPK3	0.015	0.001	-10000	0	-10000	0	0
MAPK1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.007	0.068	-10000	0	-0.56	7	7
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.047	0.11	-10000	0	-0.91	1	1
RARA	-0.002	0.087	-10000	0	-0.27	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.019	0.15	-10000	0	-0.56	25	25
PRKCA	0.014	0.046	-10000	0	-0.7	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.017	0.15	-10000	0	-0.64	6	6
RXRG	-0.059	0.18	-10000	0	-0.37	109	109
RXRA	0.008	0.083	-10000	0	-0.33	1	1
RXRB	-0.014	0.12	-10000	0	-0.35	57	57
VDR/Vit D3/DNA	-0.002	0.026	-10000	0	-0.42	2	2
RBP1	-0.18	0.35	-10000	0	-0.82	117	117
CRBP1/9-cic-RA	-0.15	0.27	-10000	0	-0.63	117	117
RARB	-0.035	0.17	-10000	0	-0.57	43	43
PRKCG	-0.079	0.26	-10000	0	-0.82	55	55
MNAT1	0.014	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.018	0.15	-10000	0	-0.54	5	5
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.007	0.13	-10000	0	-0.55	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.002	0.11	-10000	0	-0.41	17	17
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.017	0.15	-10000	0	-0.64	6	6
positive regulation of DNA binding	-0.022	0.058	-10000	0	-10000	0	0
NRIP1	-0.015	0.15	-10000	0	-1.4	2	2
RXRs/RARs	-0.024	0.15	-10000	0	-0.47	18	18
RXRs/RXRs/DNA/9cRA	-0.048	0.11	-10000	0	-0.46	9	9
PRKACA	0.014	0	-10000	0	-10000	0	0
CDK7	0.014	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.016	0.042	-10000	0	-10000	0	0
CCNH	0.014	0	-10000	0	-10000	0	0
CREBBP	0.014	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0.011	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.21	-9999	-0.65	4	4
CRP	-0.031	0.24	-9999	-0.74	20	20
cell cycle arrest	-0.023	0.23	-9999	-0.68	12	12
TIMP1	-0.005	0.2	-9999	-0.76	7	7
IL6ST	-0.057	0.19	-9999	-0.56	62	62
Rac1/GDP	-0.009	0.15	-9999	-0.56	15	15
AP1	0.007	0.13	-9999	-0.59	3	3
GAB2	0.011	0.045	-9999	-0.57	3	3
TNFSF11	-0.08	0.31	-9999	-0.72	42	42
HSP90B1	0.03	0.05	-9999	-10000	0	0
GAB1	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.013	0.15	-9999	-0.54	17	17
AKT1	0.057	0.031	-9999	-10000	0	0
FOXO1	0.063	0.029	-9999	-10000	0	0
MAP2K6	-0.025	0.16	-9999	-0.54	21	21
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	0.001	0.16	-9999	-0.55	11	11
MITF	-0.024	0.16	-9999	-0.53	23	23
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0.037	-9999	-0.82	1	1
A2M	0.021	0.031	-9999	-0.66	1	1
CEBPB	0.02	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.015	0.075	-9999	-0.42	3	3
STAT3	-0.024	0.24	-9999	-0.7	13	13
STAT1	-0.021	0.084	-9999	-0.35	28	28
CEBPD	-0.012	0.21	-9999	-0.64	6	6
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.021	0.033	-9999	-0.4	3	3
JUN	0.014	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.014	0.15	-9999	-0.52	19	19
MAPK11	-0.013	0.15	-9999	-0.54	17	17
STAT3 (dimer)/FOXO1	0.031	0.2	-9999	-10000	0	0
GRB2/SOS1/GAB family	-0.047	0.1	-9999	-0.52	9	9
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.02	0.15	-9999	-0.53	20	20
GRB2	0.014	0.001	-9999	-10000	0	0
JAK2	0.013	0.026	-9999	-0.57	1	1
LBP	-0.11	0.37	-9999	-0.89	72	72
PIK3R1	0.012	0.045	-9999	-0.56	3	3
JAK1	0.016	0.004	-9999	-10000	0	0
MYC	-0.012	0.21	-9999	-0.64	6	6
FGG	-0.046	0.27	-9999	-0.75	31	31
macrophage differentiation	-0.023	0.23	-9999	-0.68	12	12
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.061	0.14	-9999	-0.52	25	25
JUNB	-0.012	0.2	-9999	-0.61	7	7
FOS	-0.061	0.19	-9999	-0.57	64	64
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.024	0.16	-9999	-0.49	25	25
STAT1/PIAS1	-0.022	0.15	-9999	-0.5	15	15
GRB2/SOS1/GAB family/SHP2/PI3K	0.04	0.036	-9999	-10000	0	0
STAT3 (dimer)	-0.023	0.24	-9999	-0.7	12	12
PRKCD	0.009	0.18	-9999	-0.63	5	5
IL6R	0.006	0.073	-9999	-0.57	8	8
SOCS3	-0.008	0.15	-9999	-0.75	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	-0.015	0.12	-9999	-0.36	5	5
Rac1/GTP	-0.014	0.16	-9999	-0.56	15	15
HCK	0.006	0.079	-9999	-0.77	5	5
MAPKKK cascade	0.031	0.071	-9999	-0.56	3	3
bone resorption	-0.074	0.3	-9999	-0.68	42	42
IRF1	-0.012	0.21	-9999	-0.63	7	7
mol:GDP	-0.019	0.16	-9999	-0.53	21	21
SOS1	0.013	0.004	-9999	-10000	0	0
VAV1	-0.02	0.16	-9999	-0.54	21	21
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.017	0.15	-9999	-0.62	16	16
PTPN11	-0.001	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.029	0.15	-9999	-0.45	53	53
gp130 (dimer)/TYK2/TYK2/LMO4	-0.02	0.12	-9999	-0.86	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	-0.02	0.12	-9999	-0.65	1	1
IL6	-0.042	0.19	-9999	-0.62	46	46
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	-0.036	0.15	-9999	-0.51	22	22
LMO4	0.016	0.011	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.16	-9999	-0.67	12	12
MCL1	0.063	0.028	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.14	0.32	-9999	-0.82	89	89
alphaV beta3 Integrin	-0.027	0.12	-9999	-0.57	23	23
PTK2	-0.028	0.091	-9999	-0.64	3	3
positive regulation of JNK cascade	-0.013	0.054	-9999	-0.35	3	3
CDC42/GDP	0.038	0.088	-9999	-0.39	14	14
Rac1/GDP	0.04	0.087	-9999	-0.48	3	3
RAP1B	0.012	0.037	-9999	-0.82	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.013	0.026	-9999	-0.57	1	1
CDC42/GTP	-0.016	0.066	-9999	-0.36	14	14
nectin-3/I-afadin	-0.025	0.11	-9999	-0.5	25	25
RAPGEF1	0.035	0.095	-9999	-0.44	14	14
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.11	-9999	-0.5	14	14
PDGFB-D/PDGFRB	-0.14	0.32	-9999	-0.82	89	89
TLN1	0.023	0.058	-9999	-0.47	2	2
Rap1/GTP	-0.015	0.058	-9999	-0.38	3	3
IQGAP1	0.014	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.001	0.022	-9999	-0.5	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.025	0.11	-9999	-0.5	25	25
PVR	0.01	0.053	-9999	-0.82	2	2
Necl-5(dimer)	0.01	0.053	-9999	-0.82	2	2
mol:GDP	0.035	0.1	-9999	-0.48	14	14
MLLT4	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	-0.1	0.19	-9999	-0.47	99	99
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.41	3	3
positive regulation of lamellipodium assembly	-0.018	0.061	-9999	-0.31	14	14
PVRL1	0.01	0.045	-9999	-0.57	3	3
PVRL3	-0.021	0.15	-9999	-0.68	25	25
PVRL2	0.012	0.037	-9999	-0.82	1	1
PIK3R1	0.01	0.045	-9999	-0.57	3	3
CDH1	0.008	0.058	-9999	-0.57	5	5
CLDN1	-0.014	0.13	-9999	-0.64	21	21
JAM-A/CLDN1	-0.035	0.11	-9999	-0.5	18	18
SRC	-0.026	0.1	-9999	-0.56	14	14
ITGB3	-0.015	0.14	-9999	-0.73	19	19
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.031	-9999	-0.41	3	3
FARP2	0.032	0.1	-9999	-0.48	14	14
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)	-0.024	0.1	-9999	-0.54	13	13
nectin-1/I-afadin	-0.002	0.031	-9999	-0.41	3	3
nectin-2/I-afadin	-0.001	0.028	-9999	-0.63	1	1
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.024	0.099	-9999	-0.54	11	11
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0.026	-9999	-0.57	1	1
positive regulation of filopodium formation	-0.013	0.054	-9999	-0.35	3	3
alphaV/beta3 Integrin/Talin	0.017	0.11	-9999	-0.43	17	17
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.028	-9999	-0.63	1	1
nectin-2(dimer)/I-afadin/I-afadin	-0.001	0.028	-9999	-0.63	1	1
PIP5K1C	0.017	0.053	-9999	-0.35	1	1
VAV2	0.023	0.11	-9999	-0.49	14	14
RAP1/GDP	-0.016	0.067	-9999	-0.44	3	3
ITGAV	0.006	0.079	-9999	-0.77	5	5
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.023	0.099	-9999	-0.54	12	12
nectin-3(dimer)/I-afadin/I-afadin	-0.025	0.11	-9999	-0.5	25	25
Rac1/GTP	-0.022	0.073	-9999	-0.38	14	14
PTPRM	0.008	0.058	-9999	-0.27	12	12
E-cadherin/beta catenin/alpha catenin	-0.006	0.047	-9999	-0.54	2	2
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.039	0.19	-9999	-0.87	20	20
MAP4K1	-0.008	0.13	-9999	-0.76	14	14
MAP3K8	0.01	0.045	-9999	-0.57	3	3
PRKCB	0.001	0.1	-9999	-0.79	8	8
DBNL	0.014	0	-9999	-10000	0	0
CRKL	0.012	0.037	-9999	-0.82	1	1
MAP3K1	0.027	0.1	-9999	-0.53	13	13
JUN	0.024	0.091	-9999	-0.55	9	9
MAP3K7	0.027	0.1	-9999	-0.53	13	13
GRAP2	-0.004	0.11	-9999	-0.66	13	13
CRK	0.014	0	-9999	-10000	0	0
MAP2K4	0.036	0.1	-9999	-0.5	13	13
LAT	-0.011	0.14	-9999	-0.82	15	15
LCP2	0.009	0.064	-9999	-0.82	3	3
MAPK8	0.017	0.096	-9999	-0.53	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.11	-9999	-0.57	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.037	0.18	-9999	-0.83	20	20

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.048	-9999	-0.66	2	2
VDR	0.011	0.037	-9999	-0.57	2	2
FAM120B	0.014	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.018	0.11	-9999	-0.44	4	4
RXRs/LXRs/DNA/Oxysterols	0.027	0.12	-9999	-0.45	6	6
MED1	0.012	0.037	-9999	-0.82	1	1
mol:9cRA	0.005	0.011	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.006	0.11	-9999	-0.5	3	3
RXRs/NUR77	-0.002	0.13	-9999	-0.44	12	12
RXRs/PPAR	-0.095	0.16	-9999	-0.47	20	20
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-9999	-0.42	2	2
RARs/VDR/DNA/Vit D3	-0.026	0.085	-9999	-0.52	2	2
RARA	0.014	0	-9999	-10000	0	0
NCOA1	0.014	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.037	-9999	-0.56	2	2
RARs/RARs/DNA/9cRA	-0.025	0.083	-9999	-0.47	1	1
RARG	0.013	0.026	-9999	-0.57	1	1
RPS6KB1	0.013	0.039	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.006	0.11	-9999	-0.5	3	3
THRA	0.014	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.026	-9999	-0.42	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.001	0.12	-9999	-0.46	11	11
NR1H4	0.003	0.037	-9999	-0.82	1	1
RXRs/LXRs/DNA	0.017	0.13	-9999	-0.45	14	14
NR1H2	0.019	0.008	-9999	-10000	0	0
NR1H3	0.009	0.091	-9999	-0.81	6	6
RXRs/VDR/DNA/Vit D3	0.002	0.12	-9999	-0.45	8	8
NR4A1	0.003	0.077	-9999	-0.57	9	9
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.005	0.084	-9999	-0.33	4	4
RXRG	-0.057	0.2	-9999	-0.6	60	60
RXR alpha/CCPG	0.024	0.006	-9999	-10000	0	0
RXRA	0.019	0.008	-9999	-10000	0	0
RXRB	0.019	0.009	-9999	-10000	0	0
THRB	-0.032	0.16	-9999	-0.57	39	39
PPARG	-0.21	0.28	-9999	-0.57	194	194
PPARD	0.014	0	-9999	-10000	0	0
TNF	0.015	0.18	-9999	-0.68	24	24
mol:Oxysterols	0.005	0.01	-9999	-10000	0	0
cholesterol transport	0.027	0.12	-9999	-0.44	6	6
PPARA	0.014	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.037	0.16	-9999	-0.57	43	43
RXRs/NUR77/BCL2	-0.007	0.1	-9999	-0.66	1	1
SREBF1	0.035	0.11	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.001	0.12	-9999	-0.46	11	11
ABCA1	0.031	0.13	-9999	-0.9	3	3
RARs/THRs	-0.046	0.11	-9999	-0.54	4	4
RXRs/FXR	-0.003	0.12	-9999	-0.45	12	12
BCL2	0.002	0.09	-9999	-0.69	8	8

×

FAS signaling pathway (CD95)

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
SPTAN1	0.007	0.037	0.26	4	-10000	0	4
RFC1	0.007	0.037	0.26	4	-10000	0	4
PRKDC	0.007	0.037	0.26	4	-10000	0	4
RIPK1	0.014	0.003	-10000	0	-10000	0	0
CASP7	-0.014	0.039	0.23	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.055	0.12	-10000	0	-0.39	13	13
MAP2K4	-0.007	0.13	-10000	0	-0.43	11	11
mol:ceramide	-0.029	0.14	-10000	0	-0.48	13	13
GSN	0.007	0.037	0.26	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 8	-0.026	0.13	-10000	0	-0.44	9	9
FAS	0.011	0.037	-10000	0	-0.57	2	2
BID	0.002	0.047	0.3	1	-0.56	2	3
MAP3K1	0.007	0.079	-10000	0	-10000	0	0
MAP3K7	0.013	0.004	-10000	0	-10000	0	0
RB1	0.005	0.043	0.26	4	-0.33	2	6
CFLAR	0.014	0.003	-10000	0	-10000	0	0
HGF/MET	-0.029	0.11	-10000	0	-0.58	9	9
ARHGDIB	0.007	0.037	-10000	0	-10000	0	0
FADD	-0.085	0.27	-10000	0	-0.82	59	59
actin filament polymerization	-0.007	0.037	-10000	0	-0.26	4	4
NFKB1	-0.031	0.061	-10000	0	-10000	0	0
MAPK8	-0.014	0.16	-10000	0	-0.58	9	9
DFFA	0.007	0.037	0.26	4	-10000	0	4
DNA fragmentation during apoptosis	0.005	0.046	0.26	4	-0.43	2	6
FAS/FADD/MET	-0.071	0.19	-10000	0	-0.56	62	62
CFLAR/RIP1	0.001	0.005	-10000	0	-10000	0	0
FAIM3	0.001	0.1	-10000	0	-0.79	8	8
FAF1	0.014	0.004	-10000	0	-10000	0	0
PARP1	0.007	0.037	0.26	4	-10000	0	4
DFFB	0.005	0.047	0.26	4	-0.43	2	6
CHUK	-0.026	0.053	-10000	0	-10000	0	0
FASLG	-0.055	0.22	-10000	0	-0.75	45	45
FAS/FADD	-0.076	0.21	-10000	0	-0.63	60	60
HGF	-0.012	0.13	-10000	0	-0.63	20	20
LMNA	0.006	0.034	-10000	0	-10000	0	0
CASP6	0.007	0.037	-10000	0	-10000	0	0
CASP10	0.014	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.044	0.3	8	-10000	0	8
PTPN13	0	0.089	-10000	0	-0.57	12	12
CASP8	0.006	0.048	0.38	8	-10000	0	8
IL6	-0.083	0.35	-10000	0	-1.1	46	46
MET	0.005	0.083	-10000	0	-0.74	6	6
ICAD/CAD	0.005	0.044	-10000	0	-0.49	1	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.03	0.14	-10000	0	-0.48	13	13
activation of caspase activity by cytochrome c	0.002	0.047	0.3	1	-0.55	2	3
PAK2	0.007	0.037	0.26	4	-10000	0	4
BCL2	0.002	0.09	-10000	0	-0.69	8	8

×

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	0.042	0.099	-10000	0	-0.65	4	4
UGCG	-0.008	0.12	-10000	0	-0.62	17	17
AKT1/mTOR/p70S6K/Hsp90/TERT	0.015	0.13	-10000	0	-0.4	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.001	0.12	-10000	0	-0.62	17	17
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.022	0.075	-10000	0	-0.45	7	7
FRAP1	0.054	0.12	-10000	0	-0.49	10	10
FOXO3	0.062	0.1	-10000	0	-0.5	4	4
AKT1	0.055	0.11	-10000	0	-0.53	5	5
GAB2	0.011	0.045	-10000	0	-0.57	3	3
SMPD1	0.014	0.025	-10000	0	-10000	0	0
SGMS1	0.014	0.025	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0.029	-10000	0	-0.35	3	3
CALM1	0.014	0	-10000	0	-10000	0	0
cell proliferation	0.03	0.082	-10000	0	-0.42	6	6
EIF3A	0.014	0	-10000	0	-10000	0	0
PI3K	0.022	0.034	-10000	0	-0.41	3	3
RPS6KB1	0.007	0.068	-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	-0.012	0.15	-10000	0	-0.82	17	17
PIK3R1	0.013	0.045	-10000	0	-0.57	3	3
JAK1	0.017	0.002	-10000	0	-10000	0	0
NFKB1	0.014	0	-10000	0	-10000	0	0
MYC	0.062	0.096	-10000	0	-0.57	1	1
MYB	-0.1	0.37	-10000	0	-1.2	52	52
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.042	0.12	-10000	0	-0.54	9	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.022	0.063	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.042	0.11	-10000	0	-0.53	9	9
Rac1/GDP	0.029	0.026	-10000	0	-10000	0	0
T cell proliferation	0.051	0.11	-10000	0	-0.5	8	8
SHC1	0.015	0.002	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.001	0.022	-10000	0	-0.065	52	52
PRKCZ	0.051	0.11	-10000	0	-0.52	8	8
NF kappa B1 p50/RelA	-0.02	0.074	-10000	0	-0.48	4	4
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.035	0.11	-10000	0	-0.51	13	13
HSP90AA1	0.014	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
IL2RA	-0.063	0.24	-10000	0	-0.82	46	46
IL2RB	0.006	0.095	-10000	0	-0.78	7	7
TERT	-0.17	0.34	-10000	0	-0.82	108	108
E2F1	-0.034	0.15	-10000	0	-0.42	53	53
SOS1	0.014	0.002	-10000	0	-10000	0	0
RPS6	0.014	0	-10000	0	-10000	0	0
mol:cAMP	0	0.011	0.031	52	-10000	0	52
PTPN11	0.015	0.002	-10000	0	-10000	0	0
IL2RG	-0.01	0.15	-10000	0	-0.79	17	17
actin cytoskeleton organization	0.051	0.11	-10000	0	-0.5	8	8
GRB2	0.014	0.002	-10000	0	-10000	0	0
IL2	0.007	0.038	-10000	0	-0.82	1	1
PIK3CA	0.017	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.028	-10000	0	-10000	0	0
LCK	-0.003	0.13	-10000	0	-0.82	12	12
BCL2	0.054	0.14	-10000	0	-0.73	9	9

×

IGF1 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
NCK2	0.014	0	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
CRKL	-0.026	0.12	-9999	-0.42	6	6
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.012	0.037	-9999	-0.82	1	1
IRS1/Crk	-0.025	0.12	-9999	-0.41	5	5
IGF-1R heterotetramer/IGF1/PTP1B	-0.056	0.12	-9999	-0.47	5	5
AKT1	0	0.11	-9999	-0.47	3	3
BAD	0.009	0.1	-9999	-0.44	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.025	0.12	-9999	-0.41	5	5
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.026	0.12	-9999	-0.41	5	5
RAF1	0.014	0.099	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.045	0.099	-9999	-0.51	1	1
YWHAZ	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.037	0.13	-9999	-0.31	85	85
PIK3CA	0.014	0	-9999	-10000	0	0
RPS6KB1	0	0.11	-9999	-0.47	3	3
GNB2L1	0.014	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.011	0.088	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.039	0.089	-9999	-0.55	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.041	0.092	-9999	-10000	0	0
IGF-1R heterotetramer	0.002	0.028	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.025	0.12	-9999	-0.41	5	5
Crk/p130 Cas/Paxillin	-0.042	0.092	-9999	-0.48	1	1
IGF1R	0.002	0.028	-9999	-10000	0	0
IGF1	-0.089	0.23	-9999	-0.59	85	85
IRS2/Crk	-0.016	0.12	-9999	-0.52	2	2
PI3K	-0.047	0.1	-9999	-0.53	3	3
apoptosis	-0.016	0.092	-9999	-10000	0	0
HRAS/GDP	-0.001	0.029	-9999	-0.64	1	1
PRKCD	-0.023	0.15	-9999	-0.54	1	1
RAF1/14-3-3 E	0.021	0.09	-9999	-10000	0	0
BAD/14-3-3	0.016	0.096	-9999	-10000	0	0
PRKCZ	0	0.11	-9999	-0.47	3	3
Crk/p130 Cas/Paxillin/FAK1	-0.032	0.07	-9999	-10000	0	0
PTPN1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.033	0.16	-9999	-0.38	81	81
BCAR1	0.014	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.048	0.11	-9999	-0.44	5	5
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.014	0	-9999	-10000	0	0
IRS1/NCK2	-0.025	0.12	-9999	-0.41	5	5
GRB10	0.012	0.037	-9999	-0.82	1	1
PTPN11	-0.025	0.12	-9999	-0.41	5	5
IRS1	-0.037	0.13	-9999	-0.31	85	85
IRS2	-0.026	0.12	-9999	-0.44	6	6
IGF-1R heterotetramer/IGF1	-0.074	0.16	-9999	-0.43	85	85
GRB2	0.014	0	-9999	-10000	0	0
PDPK1	-0.009	0.11	-9999	-0.5	3	3
YWHAE	0.014	0	-9999	-10000	0	0
PRKD1	-0.028	0.16	-9999	-0.37	84	84
SHC1	0.014	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.038	0.099	-10000	0	-0.48	1	1
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.029	-10000	0	-0.64	1	1
GNB1/GNG2	-0.001	0.025	-10000	0	-0.55	1	1
GNB1	0.014	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.042	0.11	-10000	0	-0.32	64	64
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.011	0.028	0.084	64	-10000	0	64
GNAL	-0.061	0.19	-10000	0	-0.57	64	64
GNG2	0.012	0.037	-10000	0	-0.82	1	1
CRH	-0.001	0.037	-10000	0	-0.82	1	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.043	-10000	0	-0.35	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	0.16	0.32	-9999	-1.2	3	3
PLK1	0.084	0.085	-9999	-0.7	2	2
BIRC5	0.059	0.16	-9999	-0.62	22	22
HSPA1B	0.15	0.32	-9999	-1.2	3	3
MAP2K1	0.046	0.037	-9999	-10000	0	0
BRCA2	0.15	0.34	-9999	-1.3	6	6
FOXM1	0.15	0.36	-9999	-1.5	5	5
XRCC1	0.16	0.32	-9999	-1.2	3	3
FOXM1B/p19	-0.18	0.27	-9999	-1	20	20
Cyclin D1/CDK4	0.1	0.37	-9999	-1.1	7	7
CDC2	0.15	0.33	-9999	-1.2	5	5
TGFA	0.11	0.36	-9999	-1	11	11
SKP2	0.16	0.32	-9999	-1.2	4	4
CCNE1	0.008	0.098	-9999	-0.81	7	7
CKS1B	0.15	0.33	-9999	-1.2	6	6
RB1	-0.049	0.11	-9999	-0.72	5	5
FOXM1C/SP1	0.14	0.32	-9999	-1.3	5	5
AURKB	0.075	0.12	-9999	-0.66	9	9
CENPF	0.16	0.32	-9999	-1.2	3	3
CDK4	0.024	0.017	-9999	-10000	0	0
MYC	0.16	0.29	-9999	-1	3	3
CHEK2	0.046	0.037	-9999	-10000	0	0
ONECUT1	0.099	0.38	-9999	-1.1	11	11
CDKN2A	-0.36	0.39	-9999	-0.77	230	230
LAMA4	0.14	0.35	-9999	-1.1	7	7
FOXM1B/HNF6	0.093	0.42	-9999	-1.3	12	12
FOS	0.051	0.5	-9999	-1.1	65	65
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	0.14	0.34	-9999	-1.2	4	4
response to radiation	0.027	0.035	-9999	-10000	0	0
CENPB	0.16	0.32	-9999	-1.2	3	3
CENPA	0.15	0.33	-9999	-1.3	4	4
NEK2	0.15	0.32	-9999	-1.3	3	3
HIST1H2BA	0.15	0.32	-9999	-1.2	3	3
CCNA2	0.018	0.039	-9999	-0.84	1	1
EP300	0.011	0.037	-9999	-0.57	2	2
CCNB1/CDK1	0.15	0.34	-9999	-1.4	4	4
CCNB2	0.15	0.32	-9999	-1.4	3	3
CCNB1	0.16	0.33	-9999	-1.2	4	4
ETV5	0.15	0.32	-9999	-1.2	3	3
ESR1	0.12	0.38	-9999	-1	21	21
CCND1	0.1	0.38	-9999	-1.1	12	12
GSK3A	0.042	0.032	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.044	0.085	-9999	-0.54	8	8
CDK2	0.02	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.032	0.04	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.071	0.19	-9999	-1.2	6	6
GAS1	0.15	0.34	-9999	-1.2	8	8
MMP2	0.11	0.38	-9999	-1.1	9	9
RB1/FOXM1C	0.12	0.36	-9999	-1.2	6	6
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	-0.58	14	14
MAP3K8	0.009	0.045	-9999	-0.57	3	3
FOS	0.009	0.12	-9999	-0.47	14	14
PRKCA	0.01	0.046	-9999	-0.69	2	2
PTPN7	-0.026	0.18	-9999	-0.82	24	24
HRAS	0.012	0.037	-9999	-0.82	1	1
PRKCB	0	0.1	-9999	-0.79	8	8
NRAS	0.014	0.001	-9999	-10000	0	0
RAS family/GTP	-0.003	0.039	-9999	-0.5	3	3
MAPK3	0.012	0.083	-9999	-0.37	12	12
MAP2K1	0.029	0.069	-9999	-0.44	5	5
ELK1	0.01	0.039	-9999	-0.85	1	1
BRAF	-0.01	0.052	-9999	-0.4	5	5
mol:GTP	-0.001	0.002	-9999	-0.006	61	61
MAPK1	0.012	0.083	-9999	-0.38	11	11
RAF1	-0.01	0.052	-9999	-0.4	5	5
KRAS	0.01	0.053	-9999	-0.82	2	2

×

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

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
BAG4	0.011	0.037	-9999	-0.57	2	2
Caspase 8 (4 units)	-0.037	0.078	-9999	-0.48	4	4
NEF	-0.01	0.051	-9999	-10000	0	0
NFKBIA	0.01	0.044	-9999	-0.81	1	1
BIRC3	0.013	0.16	-9999	-0.74	22	22
CYCS	0.003	0.11	-9999	-0.49	6	6
RIPK1	0.014	0	-9999	-10000	0	0
CD247	-0.032	0.19	-9999	-0.9	21	21
MAP2K7	0.007	0.098	-9999	-0.44	4	4
protein ubiquitination	0.029	0.1	-9999	-0.49	2	2
CRADD	0.014	0	-9999	-10000	0	0
DAXX	0.014	0	-9999	-10000	0	0
FAS	0.011	0.037	-9999	-0.57	2	2
BID	-0.006	0.12	-9999	-0.48	8	8
NF-kappa-B/RelA/I kappa B alpha	-0.015	0.069	-9999	-0.53	1	1
TRADD	0.014	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
CFLAR	0.014	0	-9999	-10000	0	0
FADD	-0.085	0.27	-9999	-0.82	59	59
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.015	0.069	-9999	-0.53	1	1
MAPK8	0.011	0.1	-9999	-0.43	6	6
APAF1	0.013	0.026	-9999	-0.57	1	1
TRAF1	-0.006	0.13	-9999	-0.82	12	12
TRAF2	0.002	0.098	-9999	-0.82	7	7
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.013	0.12	-9999	-0.5	6	6
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.012	0.12	-9999	-0.48	10	10
CHUK	0.028	0.11	-9999	-0.55	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.056	0.15	-9999	-0.46	59	59
TCRz/NEF	-0.055	0.18	-9999	-0.52	53	53
TNF	-0.025	0.17	-9999	-0.79	24	24
FASLG	-0.059	0.27	-9999	-0.82	52	52
NFKB1	0.012	0.025	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.026	0.11	-9999	-0.54	21	21
CASP6	-0.022	0.048	-9999	-10000	0	0
CASP7	0.035	0.13	-9999	-0.51	4	4
RELA	0.012	0.025	-9999	-10000	0	0
CASP2	0.014	0	-9999	-10000	0	0
CASP3	0.035	0.13	-9999	-0.51	4	4
TNFRSF1A	0.014	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.002	0.026	-9999	-0.41	2	2
CASP8	0.014	0	-9999	-10000	0	0
CASP9	0.014	0	-9999	-10000	0	0
MAP3K14	0.02	0.12	-9999	-0.5	5	5
APAF-1/Caspase 9	-0.042	0.1	-9999	-0.44	22	22
BCL2	0.013	0.11	-9999	-0.45	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.03	0.03	-9999	-10000	0	0
epithelial cell differentiation	-0.003	0.03	-9999	-10000	0	0
CYFIP2	0.01	0.052	-9999	-0.65	3	3
ENAH	0.064	0.047	-9999	-0.53	1	1
EGFR	-0.017	0.15	-9999	-0.76	20	20
EPHA2	0.004	0.073	-9999	-0.57	8	8
MYO6	0.037	0.035	-9999	-10000	0	0
CTNNB1	0.013	0.026	-9999	-0.57	1	1
ABI1/Sra1/Nap1	-0.004	0.04	-9999	-0.54	2	2
AQP5	-0.31	0.21	-9999	-0.45	341	341
CTNND1	0.014	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.037	0.032	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.002	0.12	-9999	-0.44	31	31
EGF	-0.094	0.23	-9999	-0.57	91	91
NCKAP1	0.012	0.037	-9999	-0.82	1	1
AQP3	-0.12	0.2	-9999	-0.69	5	5
cortical microtubule organization	-0.003	0.03	-9999	-10000	0	0
GO:0000145	0.036	0.031	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.031	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GDP	-0.007	0.043	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.043	-9999	-0.49	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.049	0.034	-9999	-10000	0	0
PVRL2	0.012	0.037	-9999	-0.82	1	1
ZYX	0.037	0.033	-9999	-10000	0	0
ARF6/GTP	-0.005	0.039	-9999	-0.45	1	1
CDH1	0.008	0.058	-9999	-0.57	5	5
EGFR/EGFR/EGF/EGF	-0.064	0.13	-9999	-0.55	6	6
RhoA/GDP	-0.003	0.028	-9999	-10000	0	0
actin cytoskeleton organization	0.043	0.034	-9999	-10000	0	0
IGF-1R heterotetramer	0.014	0	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
IGF1R	0.014	0	-9999	-10000	0	0
IGF1	-0.088	0.22	-9999	-0.58	85	85
DIAPH1	-0.003	0.04	-9999	-0.57	2	2
Wnt receptor signaling pathway	0.003	0.03	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.007	0.043	-9999	-10000	0	0
CTNNA1	0.014	0	-9999	-10000	0	0
VCL	0.043	0.035	-9999	-10000	0	0
EFNA1	0.012	0.037	-9999	-0.82	1	1
LPP	0.043	0.04	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.008	0.051	-9999	-0.52	2	2
SEC6/SEC8	-0.003	0.029	-9999	-10000	0	0
MGAT3	0.002	0.13	-9999	-0.44	31	31
HGF/MET	-0.019	0.084	-9999	-0.69	3	3
HGF	-0.012	0.13	-9999	-0.63	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.03	0.03	-9999	-10000	0	0
actin cable formation	0.082	0.041	-9999	-0.36	1	1
KIAA1543	0.018	0.11	-9999	-0.65	6	6
KIFC3	0.037	0.033	-9999	-10000	0	0
NCK1	0.014	0	-9999	-10000	0	0
EXOC3	0.014	0	-9999	-10000	0	0
ACTN1	0.036	0.039	-9999	-0.44	1	1
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.003	0.03	-9999	-10000	0	0
EXOC4	0.014	0	-9999	-10000	0	0
STX4	0.037	0.033	-9999	-10000	0	0
PIP5K1C	0.037	0.033	-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	-0.65	6	6
IGF-1R heterotetramer/IGF1	-0.046	0.099	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.028	-9999	-0.63	1	1
MET	0.005	0.083	-9999	-0.74	6	6
PLEKHA7	0.018	0.088	-9999	-0.55	4	4
mol:GTP	-0.006	0.043	-9999	-0.49	1	1
establishment of epithelial cell apical/basal polarity	0.063	0.035	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.03	0.03	-9999	-10000	0	0
regulation of cell-cell adhesion	0.043	0.034	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.03	0.03	-9999	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.14	0.32	-9999	-0.82	89	89
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.022	0.069	-9999	-0.57	2	2
GNAO1	0.009	0.071	-9999	-0.77	4	4
S1P/S1P3/G12/G13	0.023	0.052	-9999	-0.4	7	7
AKT1	-0.048	0.098	-9999	-0.38	8	8
AKT3	0.035	0.11	-9999	-0.69	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.14	0.32	-9999	-0.82	89	89
GNAI2	0.015	0.002	-9999	-10000	0	0
GNAI3	0.015	0.002	-9999	-10000	0	0
GNAI1	0.014	0.026	-9999	-0.56	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.009	0.065	-9999	-0.62	5	5
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.03	0.082	-9999	-0.62	4	4
MAPK3	0.037	0.078	-9999	-0.59	4	4
MAPK1	0.037	0.078	-9999	-0.59	4	4
JAK2	0.033	0.098	-9999	-0.53	8	8
CXCR4	0.02	0.13	-9999	-0.55	19	19
FLT1	0.015	0.037	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.037	0.078	-9999	-0.59	4	4
S1P/S1P3/Gi	0.03	0.082	-9999	-0.63	4	4
RAC1	0.014	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.064	-9999	-0.57	4	4
VEGFA	0.007	0.091	-9999	-0.82	6	6
S1P/S1P2/Gi	0.031	0.064	-9999	-0.59	2	2
VEGFR1 homodimer/VEGFA homodimer	0.02	0.077	-9999	-0.62	7	7
RHOA	0.014	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.015	0.12	-9999	-0.52	6	6
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.015	0.15	-9999	-0.74	20	20
G12/G13	-0.003	0.04	-9999	-0.63	2	2
GNA14	-0.075	0.21	-9999	-0.57	76	76
GNA15	0.011	0.037	-9999	-0.57	2	2
GNA12	0.01	0.053	-9999	-0.82	2	2
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.052	-9999	-0.57	4	4
Rac1/GTP	-0.014	0.064	-9999	-0.57	4	4

×

Aurora B signaling

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
Condensin I complex	0.031	0.047	-9999	-10000	0	0
STMN1	0.012	0.11	-9999	-0.71	11	11
Aurora B/RasGAP/Survivin	-0.008	0.16	-9999	-0.63	26	26
Chromosomal passenger complex/Cul3 protein complex	0.022	0.082	-9999	-0.44	10	10
BIRC5	-0.021	0.17	-9999	-0.82	22	22
DES	-0.32	0.27	-9999	-0.55	274	274
Aurora C/Aurora B/INCENP	0.01	0.091	-9999	-0.52	13	13
Aurora B/TACC1	0.006	0.078	-9999	-0.5	11	11
Aurora B/PP2A	0.007	0.086	-9999	-0.62	9	9
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.016	0.023	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.004	0.12	-9999	-0.63	18	18
Cul3 protein complex	-0.007	0.047	-9999	-10000	0	0
KIF2C	0.02	0.044	-9999	-0.27	7	7
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	0.006	0.094	-9999	-0.63	10	10
SEPT1	-0.003	0.12	-9999	-0.82	10	10
SMC2	0.014	0	-9999	-10000	0	0
SMC4	0.012	0.037	-9999	-0.82	1	1
NSUN2/NPM1/Nucleolin	0.025	0.054	-9999	-0.39	5	5
PSMA3	0.014	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	0.015	0.051	-9999	-0.36	9	9
AURKB	0.006	0.11	-9999	-0.82	9	9
AURKC	0.005	0.083	-9999	-0.74	6	6
CDCA8	0.014	0.038	-9999	-0.83	1	1
cytokinesis	-0.022	0.087	-9999	-0.55	8	8
Aurora B/Septin1	0.005	0.12	-9999	-0.52	15	15
AURKA	-0.005	0.12	-9999	-0.82	11	11
INCENP	0.015	0.003	-9999	-10000	0	0
KLHL13	0.009	0.052	-9999	-0.57	4	4
BUB1	0.013	0.001	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.004	0.14	-9999	-0.57	26	26
EVI5	0.015	0.002	-9999	-10000	0	0
RhoA/GTP	-0.011	0.054	-9999	-0.42	6	6
SGOL1	0.014	0	-9999	-10000	0	0
CENPA	0.018	0.081	-9999	-0.44	11	11
NCAPG	0.014	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.007	0.086	-9999	-0.62	9	9
NCAPD2	0.009	0.064	-9999	-0.82	3	3
Aurora B/PP1-gamma	0.007	0.086	-9999	-0.62	9	9
RHOA	0.014	0	-9999	-10000	0	0
NCAPH	0.009	0.064	-9999	-0.82	3	3
NPM1	0.005	0.057	-9999	-0.41	9	9
RASA1	0.011	0.037	-9999	-0.57	2	2
KLHL9	0.007	0.063	-9999	-0.57	6	6
mitotic prometaphase	0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.086	-9999	-0.62	9	9
PPP1CC	0.014	0	-9999	-10000	0	0
Centraspindlin	-0.012	0.06	-9999	-0.46	6	6
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	0.005	0.057	-9999	-0.41	9	9
MYLK	0.009	0.074	-9999	-0.38	16	16
KIF23	0.015	0.002	-9999	-10000	0	0
VIM	0.013	0.1	-9999	-0.67	11	11
RACGAP1	0.015	0.002	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.005	0.057	-9999	-0.41	9	9
Chromosomal passenger complex	0.026	0.073	-9999	-0.46	7	7
Chromosomal passenger complex/EVI5	0.028	0.15	-9999	-0.54	26	26
TACC1	0.011	0.037	-9999	-0.57	2	2
PPP2R5D	0.014	0	-9999	-10000	0	0
CUL3	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.004	-9999	-10000	0	0
CLOCK	0.01	0.063	-9999	-0.56	6	6
TIMELESS/CRY2	0.046	0.013	-9999	-10000	0	0
DEC1/BMAL1	-0.11	0.24	-9999	-0.63	88	88
ATR	0.014	0	-9999	-10000	0	0
NR1D1	0.044	0.016	-9999	-10000	0	0
ARNTL	0.017	0	-9999	-10000	0	0
TIMELESS	0.044	0.016	-9999	-10000	0	0
NPAS2	0.008	0.073	-9999	-0.56	8	8
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	0.013	0.026	-9999	-0.57	1	1
BMAL/CLOCK/NPAS2	0.036	0.065	-9999	-0.65	1	1
BMAL1/CLOCK	0.007	0.11	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.051	0.013	-9999	-10000	0	0
mol:NADPH	0.015	0	-9999	-10000	0	0
PER1/TIMELESS	0.045	0.02	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.14	0.32	-9999	-0.82	88	88

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.071	-10000	0	-0.63	6	6
MAP4K4	0.029	0.082	-10000	0	-0.4	9	9
BAG4	0.011	0.037	-10000	0	-0.57	2	2
PKC zeta/ceramide	-0.014	0.042	0.19	5	-0.35	1	6
NFKBIA	0.012	0.037	-10000	0	-0.82	1	1
BIRC3	-0.021	0.17	-10000	0	-0.82	21	21
BAX	-0.002	0.021	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AKT1	0.022	0.009	-10000	0	-10000	0	0
BAD	-0.012	0.04	0.21	5	-10000	0	5
SMPD1	0.019	0.054	-10000	0	-0.26	4	4
RB1	-0.013	0.046	0.21	5	-0.35	2	7
FADD/Caspase 8	-0.015	0.17	-10000	0	-0.44	61	61
MAP2K4	-0.004	0.038	0.23	1	-10000	0	1
NSMAF	0.014	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.004	0.038	-10000	0	-10000	0	0
EGF	-0.094	0.23	-10000	0	-0.57	91	91
mol:ceramide	-0.023	0.043	0.22	5	-10000	0	5
MADD	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.071	-10000	0	-0.63	6	6
ASAH1	0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.014	0.045	0.21	5	-0.34	2	7
cell proliferation	-0.046	0.092	-10000	0	-0.39	4	4
BID	0.02	0.058	-10000	0	-10000	0	0
MAP3K1	-0.012	0.04	0.21	5	-10000	0	5
EIF2A	0.001	0.05	-10000	0	-0.44	3	3
TRADD	0.014	0	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
MAPK3	0.009	0.036	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.036	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.013	0.039	0.19	5	-10000	0	5
FADD	-0.029	0.18	-10000	0	-0.47	66	66
KSR1	-0.012	0.04	0.21	5	-10000	0	5
MAPK8	-0.002	0.05	0.21	5	-0.26	8	13
PRKRA	-0.012	0.04	0.23	1	-10000	0	1
PDGFA	0.004	0.091	-10000	0	-0.82	6	6
TRAF2	0.002	0.098	-10000	0	-0.82	7	7
IGF1	-0.088	0.22	-10000	0	-0.58	85	85
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.023	0.043	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	-0.029	0.11	-10000	0	-0.42	4	4
PRKCD	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.013	0.026	-10000	0	-0.57	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.071	-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	0.022	0.086	-10000	0	-0.43	9	9
TNFR1A/BAG4/TNF-alpha	-0.026	0.11	-10000	0	-0.54	21	21
mol:Sphingosine-1-phosphate	0.017	0.071	-10000	0	-0.63	6	6
MAP2K1	0.004	0.037	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.014	0	-10000	0	-10000	0	0
CYCS	-0.003	0.034	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	0.026	-10000	0	-0.41	2	2
EIF2AK2	-0.007	0.053	-10000	0	-0.47	3	3
TNF-alpha/TNFR1A/FAN	-0.025	0.11	-10000	0	-0.54	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.034	0.048	-10000	0	-10000	0	0
MAP2K2	0.004	0.037	-10000	0	-10000	0	0
SMPD3	0.002	0.099	-10000	0	-0.33	31	31
TNF	-0.025	0.17	-10000	0	-0.79	24	24
PKC zeta/PAR4	-0.001	0.018	-10000	0	-0.41	1	1
mol:PHOSPHOCHOLINE	0.029	0.096	0.22	94	-10000	0	94
NF kappa B1/RelA/I kappa B alpha	-0.001	0.024	-10000	0	-0.46	1	1
AIFM1	-0.003	0.034	0.33	1	-10000	0	1
BCL2	0.002	0.09	-10000	0	-0.69	8	8

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0.014	0	-9999	-10000	0	0
SPHK1	-0.006	0.13	-9999	-0.82	12	12
GNAI2	0.014	0	-9999	-10000	0	0
mol:S1P	0.015	0.053	-9999	-0.29	15	15
GNAO1	0.008	0.069	-9999	-0.76	4	4
mol:Sphinganine-1-P	0.009	0.1	-9999	-0.63	12	12
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.007	0.043	-9999	-0.46	2	2
GNAI3	0.014	0	-9999	-10000	0	0
G12/G13	-0.003	0.04	-9999	-0.63	2	2
S1PR3	0.007	0.064	-9999	-0.62	5	5
S1PR2	0.014	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.007	0.042	-9999	-10000	0	0
S1PR5	0.008	0.064	-9999	-0.69	4	4
S1PR4	-0.034	0.19	-9999	-0.81	29	29
GNAI1	0.013	0.026	-9999	-0.57	1	1
S1P/S1P5/G12	0.022	0.065	-9999	-0.48	4	4
S1P/S1P3/Gq	-0.011	0.12	-9999	-0.51	7	7
S1P/S1P4/Gi	0.014	0.094	-9999	-0.47	5	5
GNAQ	0.014	0	-9999	-10000	0	0
GNAZ	-0.017	0.15	-9999	-0.74	20	20
GNA14	-0.075	0.21	-9999	-0.57	76	76
GNA15	0.011	0.037	-9999	-0.57	2	2
GNA12	0.01	0.053	-9999	-0.82	2	2
GNA13	0.014	0	-9999	-10000	0	0
GNA11	0.009	0.052	-9999	-0.57	4	4
ABCC1	0.009	0.064	-9999	-0.82	3	3

×

a4b1 and a4b7 Integrin 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
ITGB1	0.012	0.037	-9999	-0.82	1	1
ITGB7	0.011	0.037	-9999	-0.57	2	2
ITGA4	-0.005	0.12	-9999	-0.82	11	11
alpha4/beta7 Integrin	-0.016	0.096	-9999	-0.59	13	13
alpha4/beta1 Integrin	-0.015	0.096	-9999	-0.63	12	12

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.005	0.16	-10000	0	-0.65	29	29
regulation of axonogenesis	-0.02	0.038	-10000	0	-10000	0	0
myoblast fusion	0.008	0.087	0.32	29	-10000	0	29
mol:GTP	-0.014	0.046	-10000	0	-0.25	3	3
regulation of calcium-dependent cell-cell adhesion	-0.018	0.065	0.35	7	-10000	0	7
ARF1/GTP	-0.009	0.031	-10000	0	-10000	0	0
mol:GM1	0	0.037	-10000	0	-10000	0	0
mol:Choline	0.019	0.043	-10000	0	-0.34	3	3
lamellipodium assembly	-0.026	0.08	-10000	0	-0.32	29	29
MAPK3	0.013	0.069	-10000	0	-0.3	3	3
ARF6/GTP/NME1/Tiam1	0.018	0.065	-10000	0	-0.35	7	7
ARF1	0.014	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.087	-10000	0	-0.32	29	29
ARF1/GDP	0.003	0.081	-10000	0	-0.49	3	3
ARF6	0.005	0.026	-10000	0	-10000	0	0
RAB11A	0.014	0	-10000	0	-10000	0	0
TIAM1	0.008	0.063	-10000	0	-0.56	6	6
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.069	-10000	0	-10000	0	0
actin filament bundle formation	0.023	0.071	0.49	3	-10000	0	3
KALRN	-0.04	0.1	-10000	0	-0.33	42	42
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.023	0.072	-10000	0	-0.49	3	3
NME1	0.013	0.037	-10000	0	-0.82	1	1
Rac1/GDP	-0.023	0.072	-10000	0	-0.49	3	3
substrate adhesion-dependent cell spreading	-0.014	0.046	-10000	0	-0.25	3	3
cortical actin cytoskeleton organization	-0.026	0.081	-10000	0	-0.32	29	29
RAC1	0.014	0	-10000	0	-10000	0	0
liver development	-0.014	0.046	-10000	0	-0.25	3	3
ARF6/GTP	-0.014	0.046	-10000	0	-0.25	3	3
RhoA/GTP	-0.009	0.031	-10000	0	-10000	0	0
mol:GDP	-0.026	0.082	-10000	0	-0.32	29	29
ARF6/GTP/RAB11FIP3/RAB11A	-0.005	0.025	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
PLD1	0.009	0.049	-10000	0	-0.4	3	3
RAB11FIP3	0.014	0	-10000	0	-10000	0	0
tube morphogenesis	-0.026	0.08	-10000	0	-0.32	29	29
ruffle organization	0.02	0.038	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.014	0.046	-10000	0	-0.25	3	3
PLD2	0.011	0.037	-10000	0	-10000	0	0
PIP5K1A	0.02	0.038	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.019	0.043	-10000	0	-0.34	3	3
Rac1/GTP	-0.026	0.081	-10000	0	-0.32	29	29

×

HIF-2-alpha transcription factor network

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
MMP14	-0.007	0.094	-10000	0	-0.69	9	9
oxygen homeostasis	-0.002	0.017	-10000	0	-10000	0	0
TCEB2	0.01	0.053	-10000	0	-0.82	2	2
TCEB1	0.012	0.037	-10000	0	-0.82	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.024	0.082	-10000	0	-0.54	3	3
EPO	-0.049	0.28	-10000	0	-0.73	37	37
FIH (dimer)	0.011	0.016	-10000	0	-10000	0	0
APEX1	0.014	0.015	-10000	0	-10000	0	0
SERPINE1	-0.26	0.39	-10000	0	-0.84	48	48
FLT1	0.005	0.044	-10000	0	-0.58	1	1
ADORA2A	-0.025	0.24	-10000	0	-0.81	7	7
germ cell development	-0.043	0.27	-10000	0	-0.81	21	21
SLC11A2	-0.021	0.23	-10000	0	-0.81	6	6
BHLHE40	-0.023	0.24	-10000	0	-0.86	6	6
HIF1AN	0.011	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.064	0.1	-10000	0	-0.49	9	9
ETS1	0.025	0.065	-10000	0	-0.81	3	3
CITED2	-0.001	0.067	-10000	0	-0.94	2	2
KDR	0.003	0.075	-10000	0	-0.99	2	2
PGK1	-0.021	0.23	-10000	0	-0.85	5	5
SIRT1	0.012	0.026	-10000	0	-0.57	1	1
response to hypoxia	-0.001	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.032	0.27	-10000	0	-0.88	11	11
EPAS1	0.005	0.13	-10000	0	-0.42	10	10
SP1	0.022	0.003	-10000	0	-10000	0	0
ABCG2	-0.028	0.24	-10000	0	-0.82	10	10
EFNA1	-0.021	0.24	-10000	0	-0.85	6	6
FXN	-0.022	0.23	-10000	0	-0.8	6	6
POU5F1	-0.047	0.28	-10000	0	-0.85	21	21
neuron apoptosis	0.031	0.26	0.84	11	-10000	0	11
EP300	0.011	0.037	-10000	0	-0.57	2	2
EGLN3	-0.038	0.2	-10000	0	-0.79	31	31
EGLN2	0.012	0.016	-10000	0	-10000	0	0
EGLN1	0.011	0.016	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.003	0.042	-10000	0	-0.54	3	3
VHL	0.014	0	-10000	0	-10000	0	0
ARNT	0.014	0.015	-10000	0	-10000	0	0
SLC2A1	-0.03	0.25	-10000	0	-0.86	14	14
TWIST1	-0.034	0.26	-10000	0	-0.83	18	18
ELK1	0.02	0.037	-10000	0	-0.81	1	1
HIF2A/ARNT/Cbp/p300	-0.053	0.096	-10000	0	-0.49	7	7
VEGFA	-0.025	0.25	-10000	0	-0.92	9	9
CREBBP	0.014	0	-10000	0	-10000	0	0

×

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	-0.046	0.11	-9999	-0.57	5	5
TC10/GTP	-0.04	0.094	-9999	-0.68	1	1
Insulin Receptor/Insulin/IRS1/Shp2	-0.004	0.04	-9999	-0.46	2	2
HRAS	0.012	0.037	-9999	-0.82	1	1
APS homodimer	0.01	0.053	-9999	-0.82	2	2
GRB14	-0.045	0.18	-9999	-0.6	47	47
FOXO3	-0.007	0.044	-9999	-0.63	2	2
AKT1	0.021	0.099	-9999	-0.47	2	2
INSR	0.014	0.026	-9999	-0.56	1	1
Insulin Receptor/Insulin	0.036	0.031	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0.037	-9999	-0.82	1	1
SORBS1	-0.078	0.21	-9999	-0.57	79	79
CRK	0.014	0	-9999	-10000	0	0
PTPN1	0.036	0.03	-9999	-10000	0	0
CAV1	-0.014	0.14	-9999	-0.48	40	40
CBL/APS/CAP/Crk-II/C3G	-0.045	0.11	-9999	-0.6	2	2
Insulin Receptor/Insulin/IRS1/NCK2	-0.004	0.04	-9999	-0.46	2	2
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.04	-9999	-0.4	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.036	-9999	-0.49	1	1
RPS6KB1	0.029	0.093	-9999	-10000	0	0
PARD6A	0.011	0.045	-9999	-0.69	2	2
CBL	0.014	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.021	-9999	-0.44	1	1
PIK3R1	0.01	0.045	-9999	-0.57	3	3
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.024	0.072	-9999	-10000	0	0
HRAS/GTP	-0.005	0.037	-9999	-10000	0	0
Insulin Receptor	0.014	0.026	-9999	-0.56	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.004	0.036	-9999	-0.42	2	2
PRKCI	-0.007	0.02	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.09	-9999	-0.51	2	2
SHC1	0.014	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.001	0.025	-9999	-10000	0	0
PI3K	-0.005	0.04	-9999	-0.41	2	2
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	0.029	-9999	-0.64	1	1
AKT2	0.021	0.099	-9999	-0.47	2	2
PRKCZ	-0.008	0.029	-9999	-0.48	1	1
SH2B2	0.01	0.053	-9999	-0.82	2	2
SHC/SHIP	0.031	0.045	-9999	-0.4	2	2
F2RL2	-0.22	0.38	-9999	-0.82	142	142
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	-0.42	2	2
RAPGEF1	0.014	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.57	2	2
NCK1	0.014	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.049	0.12	-9999	-0.64	2	2
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.003	0.039	-9999	-0.48	3	3
INPP5D	0.023	0.047	-9999	-0.43	2	2
SOS1	0.014	0	-9999	-10000	0	0
SGK1	-0.006	0.06	-9999	-0.72	3	3
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.014	0	-9999	-10000	0	0
IRS1	0.01	0.045	-9999	-0.57	3	3
p62DOK/RasGAP	-0.001	0.025	-9999	-10000	0	0
INS	0	0.052	-9999	-0.81	2	2
mol:PI-3-4-P2	0.023	0.047	-9999	-0.42	2	2
GRB2	0.014	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.11	-9999	-0.61	2	2
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	0.013	0.026	-9999	-0.57	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.033	0.031	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.041	-9999	-0.38	5	5
Insulin Receptor/Insulin/IRS3	-0.003	0.043	-9999	-0.55	3	3
Par3/Par6	-0.14	0.21	-9999	-0.47	141	141

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.004	0.086	0.71	7	-10000	0	7
PI3K Class IB/PDE3B	0.004	0.086	-10000	0	-0.71	7	7
PDE3B	0.004	0.087	-10000	0	-0.71	7	7

×

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	0	-9999	-10000	0	0
TRAF2/ASK1	-0.008	0.065	-9999	-0.55	7	7
ATM	0.013	0.026	-9999	-0.57	1	1
MAP2K3	0.017	0.049	-9999	-0.34	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.018	0.067	-9999	-0.32	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.002	0.09	-9999	-0.69	8	8
TXN	0.009	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
GADD45A	0.012	0.037	-9999	-0.82	1	1
GADD45B	0.014	0	-9999	-10000	0	0
MAP3K1	0.014	0	-9999	-10000	0	0
MAP3K6	0.013	0.026	-9999	-0.57	1	1
MAP3K7	0.014	0	-9999	-10000	0	0
MAP3K4	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.018	-9999	-0.41	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	-0.009	0.067	-9999	-0.5	9	9
TRAF2	0.002	0.098	-9999	-0.82	7	7
RAC1/OSM/MEKK3/MKK3	-0.013	0.051	-9999	-0.42	3	3
TRAF6	0.009	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.14	0.26	-9999	-0.58	127	127
CCM2	-0.001	0.11	-9999	-0.82	9	9
CaM/Ca2+/CAMKIIB	-0.091	0.16	-9999	-0.36	127	127
MAPK11	0.014	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.081	0.14	-9999	-0.5	6	6
OSM/MEKK3	-0.011	0.084	-9999	-0.63	9	9
TAOK1	0.008	0.06	-9999	-0.34	14	14
TAOK2	0.018	0.016	-9999	-0.34	1	1
TAOK3	0.018	0.016	-9999	-0.34	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.014	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAP3K10	0.014	0	-9999	-10000	0	0
MAP3K3	0.014	0	-9999	-10000	0	0
TRX/ASK1	0.017	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.007	0.053	-9999	-0.47	5	5

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.012	0.037	-10000	0	-0.82	1	1
Rac1/GDP	0.002	0.011	-10000	0	-10000	0	0
DOCK1	0.011	0.037	-10000	0	-0.57	2	2
ITGA4	-0.005	0.12	-10000	0	-0.82	11	11
RAC1	0.014	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.016	0.096	-10000	0	-0.59	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.013	0.083	-10000	0	-0.54	12	12
alpha4/beta7 Integrin/Paxillin	0.022	0.08	-10000	0	-0.49	11	11
lamellipodium assembly	-0.002	0.04	-10000	0	-0.64	1	1
PIK3CA	0.014	0	-10000	0	-10000	0	0
PI3K	-0.002	0.031	-10000	0	-0.41	3	3
ARF6	0.014	0	-10000	0	-10000	0	0
TLN1	0.01	0.053	-10000	0	-0.82	2	2
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
ARF6/GTP	-0.01	0.064	-10000	0	-10000	0	0
cell adhesion	-0.013	0.075	-10000	0	-0.46	14	14
CRKL/CBL	-0.001	0.028	-10000	0	-0.63	1	1
alpha4/beta1 Integrin/Paxillin	0.023	0.081	-10000	0	-0.49	12	12
ITGB1	0.012	0.037	-10000	0	-0.82	1	1
ITGB7	0.011	0.037	-10000	0	-0.57	2	2
ARF6/GDP	0.002	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.055	0.15	-10000	0	-0.48	52	52
p130Cas/Crk/Dock1	-0.001	0.021	-10000	0	-10000	0	0
VCAM1	-0.067	0.24	-10000	0	-0.77	51	51
alpha4/beta1 Integrin/Paxillin/Talin	-0.013	0.076	-10000	0	-0.46	14	14
alpha4/beta1 Integrin/Paxillin/GIT1	-0.011	0.071	-10000	0	-0.46	12	12
BCAR1	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.07	0.46	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	-0.013	0.076	-10000	0	-0.46	14	14
Rac1/GTP	-0.002	0.045	-10000	0	-0.74	1	1

×

IL2 signaling events mediated by STAT5

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
GAB2	0.011	0.045	-9999	-0.57	3	3
ELF1	-0.013	0.11	-9999	-0.55	4	4
CCNA2	0.012	0.037	-9999	-0.82	1	1
PIK3CA	0.015	0	-9999	-10000	0	0
JAK3	-0.014	0.15	-9999	-0.82	17	17
PIK3R1	0.011	0.045	-9999	-0.57	3	3
JAK1	0.015	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.044	0.11	-9999	-0.56	8	8
SHC1	0.015	0	-9999	-10000	0	0
SP1	0.017	0.044	-9999	-0.34	3	3
IL2RA	-0.039	0.22	-9999	-0.72	46	46
IL2RB	0.003	0.094	-9999	-0.78	7	7
SOS1	0.015	0	-9999	-10000	0	0
IL2RG	-0.013	0.15	-9999	-0.79	17	17
G1/S transition of mitotic cell cycle	0.031	0.091	-9999	-0.48	10	10
PTPN11	0.015	0	-9999	-10000	0	0
CCND2	0.021	0.098	-9999	-0.75	8	8
LCK	-0.005	0.13	-9999	-0.82	12	12
GRB2	0.015	0	-9999	-10000	0	0
IL2	0.004	0.037	-9999	-0.82	1	1
CDK6	0	0.1	-9999	-0.76	9	9
CCND3	0.052	0.099	-9999	-0.63	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.069	-9999	-0.76	4	4
CDC42/GTP	-0.023	0.073	-9999	-0.47	4	4
PLCG1	0.016	0.088	-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	-0.003	0.04	-9999	-0.63	2	2
cell migration	-0.023	0.072	-9999	-0.46	4	4
S1PR5	0.008	0.064	-9999	-0.69	4	4
S1PR4	-0.034	0.19	-9999	-0.81	29	29
MAPK3	0.016	0.088	-9999	-0.49	4	4
MAPK1	0.016	0.088	-9999	-0.49	4	4
S1P/S1P5/Gi	0.023	0.064	-9999	-0.48	2	2
GNAI1	0.013	0.026	-9999	-0.57	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.006	0.054	-9999	-0.48	6	6
RHOA	0.003	0.12	-9999	-0.46	30	30
S1P/S1P4/Gi	0.008	0.093	-9999	-0.52	4	4
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.017	0.15	-9999	-0.74	20	20
S1P/S1P4/G12/G13	-0.031	0.12	-9999	-0.5	30	30
GNA12	0.01	0.053	-9999	-0.82	2	2
GNA13	0.014	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.025	0.098	-10000	0	-0.41	31	31
ATM	0.013	0.026	-10000	0	-0.57	1	1
UBE2D3	0.014	0	-10000	0	-10000	0	0
PRKDC	0.014	0	-10000	0	-10000	0	0
ATR	0.014	0	-10000	0	-10000	0	0
UBE2L3	0.014	0	-10000	0	-10000	0	0
FANCD2	0.027	0.016	-10000	0	-0.33	1	1
protein ubiquitination	-0.024	0.09	-10000	0	-0.53	7	7
XRCC5	0.014	0	-10000	0	-10000	0	0
XRCC6	0.014	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.014	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.004	0.038	-10000	0	-0.57	1	1
FANCF	0.009	0.052	-10000	0	-0.57	4	4
BRCA1	0.014	0	-10000	0	-10000	0	0
CCNE1	0.002	0.098	-10000	0	-0.82	7	7
CDK2/Cyclin E1	-0.009	0.074	-10000	0	-0.63	7	7
FANCG	0.009	0.064	-10000	0	-0.82	3	3
BRCA1/BACH1/BARD1	-0.025	0.098	-10000	0	-0.41	31	31
FANCE	0.014	0	-10000	0	-10000	0	0
FANCC	0.014	0	-10000	0	-10000	0	0
NBN	0.014	0	-10000	0	-10000	0	0
FANCA	0.01	0.053	-10000	0	-0.82	2	2
DNA repair	0.056	0.088	-10000	0	-0.65	2	2
BRCA1/BARD1/ubiquitin	-0.025	0.098	-10000	0	-0.41	31	31
BARD1/DNA-PK	-0.019	0.072	-10000	0	-10000	0	0
FANCL	0.012	0.037	-10000	0	-0.82	1	1
mRNA polyadenylation	0.025	0.098	0.4	31	-10000	0	31
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.069	-10000	0	-0.39	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.021	0.081	-10000	0	-10000	0	0
BRCA1/BARD1/P53	-0.021	0.076	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.021	0.081	-10000	0	-10000	0	0
BRCA1/BACH1	0.014	0	-10000	0	-10000	0	0
BARD1	-0.022	0.14	-10000	0	-0.57	31	31
PCNA	0.012	0.037	-10000	0	-0.82	1	1
BRCA1/BARD1/UbcH5C	-0.021	0.081	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	-0.021	0.081	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.021	0.082	-10000	0	-0.64	2	2
BARD1/DNA-PK/P53	-0.019	0.07	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.025	0.098	-10000	0	-0.41	31	31
BRCA1/BARD1/CTIP	0.014	0.082	-10000	0	-10000	0	0
FA complex	0.038	0.041	-10000	0	-0.51	1	1
BARD1/EWS	-0.025	0.098	-10000	0	-0.41	31	31
RBBP8	0.024	0.019	-10000	0	-0.41	1	1
TP53	0.009	0.052	-10000	0	-0.57	4	4
TOPBP1	0.014	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.021	0.076	-10000	0	-10000	0	0
BRCA1/BARD1	-0.024	0.091	-10000	0	-0.54	7	7
CSTF1	0.014	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.026	0.1	-10000	0	-0.42	31	31
CDK2	0.014	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.012	0.037	-10000	0	-0.82	1	1
RAD50	0.014	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.025	0.098	-10000	0	-0.41	31	31
EWSR1	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.027	0.12	-9999	-0.57	23	23
AKT1	0.087	0.056	-9999	-0.5	1	1
PTK2B	0.033	0.12	-9999	-0.67	2	2
VEGFR2 homodimer/Frs2	0.032	0.067	-9999	-0.57	6	6
CAV1	-0.05	0.22	-9999	-0.82	38	38
CALM1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.012	0.077	-9999	-0.6	2	2
endothelial cell proliferation	0.094	0.063	-9999	-10000	0	0
mol:Ca2+	0.053	0.067	-9999	-0.54	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.008	0.06	-9999	-0.56	2	2
RP11-342D11.1	0.043	0.067	-9999	-0.54	2	2
CDH5	0.011	0.045	-9999	-0.69	2	2
VEGFA homodimer	-0.006	0.055	-9999	-0.49	6	6
SHC1	0.014	0	-9999	-10000	0	0
SHC2	0.004	0.087	-9999	-0.71	7	7
HRAS/GDP	-0.007	0.052	-9999	-10000	0	0
SH2D2A	-0.12	0.3	-9999	-0.82	78	78
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.009	0.047	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.084	0.19	-9999	-0.5	84	84
VEGFR1 homodimer	0.012	0.037	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.007	0.054	-9999	-0.53	1	1
GRB10	0.052	0.074	-9999	-0.6	3	3
PTPN11	0.014	0	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
PAK1	0.012	0.037	-9999	-0.82	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.009	0.062	-9999	-0.57	1	1
HRAS	0.012	0.037	-9999	-0.82	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.064	-9999	-0.49	2	2
HIF1A	0.013	0.026	-9999	-0.57	1	1
FRS2	0.007	0.074	-9999	-0.82	4	4
oxygen and reactive oxygen species metabolic process	-0.008	0.06	-9999	-0.55	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.003	0.094	-9999	-0.78	7	7
Nck/Pak	-0.001	0.028	-9999	-0.63	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.009	0.068	-9999	-0.5	9	9
mol:GDP	-0.007	0.053	-9999	-0.52	1	1
mol:NADP	0.073	0.06	-9999	-10000	0	0
eNOS/Hsp90	0.076	0.057	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
mol:IP3	0.053	0.068	-9999	-0.54	2	2
HIF1A/ARNT	-0.001	0.018	-9999	-0.41	1	1
SHB	0.011	0.037	-9999	-0.57	2	2
VEGFA	0.006	0.091	-9999	-0.81	6	6
VEGFC	-0.095	0.28	-9999	-0.82	65	65
FAK1/Vinculin	0.059	0.086	-9999	-0.8	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.027	0.11	-9999	-0.65	3	3
PTPN6	0.014	0	-9999	-10000	0	0
EPAS1	0.023	0.022	-9999	-10000	0	0
mol:L-citrulline	0.073	0.06	-9999	-10000	0	0
ITGAV	0.006	0.079	-9999	-0.77	5	5
PIK3CA	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.011	0.072	-9999	-0.56	2	2
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.065	-9999	-0.59	2	2
VEGFR2/3 heterodimer	0.029	0.085	-9999	-0.64	7	7
VEGFB	0.012	0.037	-9999	-0.82	1	1
MAPK11	0.055	0.067	-9999	-0.54	2	2
VEGFR2 homodimer	0.036	0.05	-9999	-0.75	2	2
FLT1	0.012	0.037	-9999	-0.82	1	1
NEDD4	0.016	0.003	-9999	-10000	0	0
MAPK3	0.057	0.066	-9999	-0.52	1	1
MAPK1	0.057	0.066	-9999	-0.52	1	1
VEGFA145/NRP2	-0.01	0.079	-9999	-0.62	8	8
VEGFR1/2 heterodimer	0.035	0.051	-9999	-0.61	3	3
KDR	0.036	0.05	-9999	-0.75	2	2
VEGFA165/NRP1/VEGFR2 homodimer	0.049	0.073	-9999	-0.54	2	2
SRC	0.014	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.059	0.066	-9999	-0.53	1	1
PI3K	-0.008	0.05	-9999	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.008	0.064	-9999	-0.51	8	8
FES	0.053	0.068	-9999	-0.55	2	2
GAB1	-0.007	0.051	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.064	-9999	-0.51	8	8
CTNNB1	0.013	0.026	-9999	-0.57	1	1
SOS1	0.014	0	-9999	-10000	0	0
ARNT	0.014	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.045	0.12	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.008	0.064	-9999	-0.51	8	8
PI3K/GAB1	0.087	0.059	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.012	0.071	-9999	-0.57	1	1
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.072	0.18	-9999	-1.1	2	2
HSP90AA1	0.014	0	-9999	-10000	0	0
CDC42	0.053	0.068	-9999	-0.55	2	2
actin cytoskeleton reorganization	-0.083	0.19	-9999	-0.49	84	84
PTK2	0.054	0.091	-9999	-0.88	1	1
EDG1	0.043	0.067	-9999	-0.54	2	2
mol:DAG	0.053	0.068	-9999	-0.54	2	2
CaM/Ca2+	-0.007	0.054	-9999	-0.53	1	1
MAP2K3	0.054	0.077	-9999	-0.55	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.052	0.076	-9999	-0.62	3	3
PLCG1	0.053	0.068	-9999	-0.55	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.009	0.062	-9999	-0.56	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.008	0.064	-9999	-0.51	8	8
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.008	0.064	-9999	-0.51	8	8
cell migration	0.082	0.077	-9999	-0.66	1	1
mol:PI-3-4-5-P3	0.073	0.06	-9999	-0.53	1	1
FYN	0.012	0.037	-9999	-0.82	1	1
VEGFB/NRP1	0.048	0.067	-9999	-0.51	2	2
mol:NO	0.073	0.06	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
HRAS/GTP	-0.007	0.052	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.052	0.076	-9999	-0.61	3	3
VHL	0.014	0	-9999	-10000	0	0
ITGB3	-0.015	0.14	-9999	-0.73	19	19
NOS3	0.075	0.065	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.014	0.082	-9999	-0.51	12	12
RAC1	0.014	0	-9999	-10000	0	0
PRKCA	0.058	0.069	-9999	-0.53	1	1
PRKCB	0.052	0.086	-9999	-0.53	1	1
VCL	0.014	0	-9999	-10000	0	0
VEGFA165/NRP1	0.043	0.068	-9999	-0.47	8	8
VEGFR1/2 heterodimer/VEGFA homodimer	-0.009	0.068	-9999	-0.56	3	3
VEGFA165/NRP2	-0.01	0.079	-9999	-0.62	8	8
MAPKKK cascade	0.074	0.068	-9999	-0.59	1	1
NRP2	0.01	0.053	-9999	-0.82	2	2
VEGFC homodimer	-0.095	0.28	-9999	-0.81	65	65
NCK1	0.014	0	-9999	-10000	0	0
ROCK1	0.014	0	-9999	-10000	0	0
FAK1/Paxillin	0.059	0.086	-9999	-0.8	1	1
MAP3K13	0.047	0.08	-9999	-0.55	2	2
PDPK1	0.078	0.057	-9999	-10000	0	0

×

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

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
MET/RANBP9	-0.007	0.062	-9999	-0.55	6	6
CRKL	0.029	0.059	-9999	-0.44	1	1
mol:PIP3	-0.023	0.004	-9999	-10000	0	0
AKT1	0	0.014	-9999	-0.3	1	1
PTK2B	0.013	0.026	-9999	-0.57	1	1
RAPGEF1	0.036	0.056	-9999	-0.41	1	1
RANBP10	0.014	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.021	0.094	-9999	-0.54	9	9
MAP3K5	0.04	0.061	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.021	0.089	-9999	-0.49	11	11
AP1	-0.03	0.13	-9999	-0.36	64	64
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0	-9999	-10000	0	0
apoptosis	-0.07	0.24	-9999	-0.7	64	64
STAT3 (dimer)	0.03	0.066	-9999	-0.48	1	1
GAB1/CRKL/SHP2/PI3K	-0.011	0.045	-9999	-0.42	1	1
INPP5D	0.01	0.045	-9999	-0.57	3	3
CBL/CRK	0.037	0.052	-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	0.029	-9999	-0.26	6	6
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.007	0.031	-9999	-10000	0	0
PAK1	0.006	0.026	-9999	-0.48	1	1
HGF/MET/RANBP10	-0.021	0.094	-9999	-0.54	9	9
HRAS	0.023	0.083	-9999	-0.6	2	2
DOCK1	0.035	0.059	-9999	-0.41	1	1
GAB1	0.023	0.057	-9999	-0.28	1	1
CRK	0.03	0.055	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.095	-9999	-0.47	17	17
JUN	0.014	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	0.004	0.053	-9999	-0.28	6	6
PIK3R1	0.01	0.045	-9999	-0.57	3	3
cell morphogenesis	0.058	0.072	-9999	-0.44	1	1
GRB2/SHC	0.021	0.048	-9999	-10000	0	0
FOS	-0.061	0.19	-9999	-0.57	64	64
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.001	0.029	-9999	-0.26	6	6
HGF/MET/MUC20	-0.022	0.095	-9999	-0.42	26	26
cell migration	0.02	0.047	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
CBL	0.014	0	-9999	-10000	0	0
MET/RANBP10	-0.007	0.062	-9999	-0.55	6	6
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.024	0.069	-9999	-0.52	1	1
MET/MUC20	-0.007	0.063	-9999	-0.56	6	6
RAP1B	0.042	0.057	-9999	-0.4	1	1
RAP1A	0.043	0.053	-9999	-10000	0	0
HGF/MET/RANBP9	-0.021	0.094	-9999	-0.54	9	9
RAF1	0.031	0.079	-9999	-0.56	2	2
STAT3	0.03	0.067	-9999	-0.49	1	1
cell proliferation	0.04	0.083	-9999	-0.44	1	1
RPS6KB1	0.011	0.02	-9999	-10000	0	0
MAPK3	-0.007	0.026	-9999	-0.26	4	4
MAPK1	-0.007	0.026	-9999	-0.26	4	4
RANBP9	0.014	0	-9999	-10000	0	0
MAPK8	0.05	0.082	-9999	-0.48	7	7
SRC	0.031	0.065	-9999	-0.48	1	1
PI3K	0.019	0.055	-9999	-0.45	1	1
MET/Glomulin	0.007	0.057	-9999	-0.5	6	6
SOS1	0.014	0	-9999	-10000	0	0
MAP2K1	0.038	0.074	-9999	-0.51	2	2
MET	0.005	0.083	-9999	-0.74	6	6
MAP4K1	0.034	0.064	-9999	-10000	0	0
PTK2	0.014	0	-9999	-10000	0	0
MAP2K2	0.038	0.074	-9999	-0.51	2	2
BAD	0.007	0.013	-9999	-10000	0	0
MAP2K4	0.047	0.057	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.048	-9999	-10000	0	0
INPPL1	0.014	0	-9999	-10000	0	0
PXN	0.014	0	-9999	-10000	0	0
SH3KBP1	0.01	0.053	-9999	-0.82	2	2
HGS	0.013	0.05	-9999	-10000	0	0
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.012	0.13	-9999	-0.63	20	20
RASA1	0.011	0.037	-9999	-0.57	2	2
NCK1	0.014	0	-9999	-10000	0	0
PTPRJ	0.014	0	-9999	-10000	0	0
NCK/PLCgamma1	0.022	0.051	-9999	-10000	0	0
PDPK1	-0.011	0.015	-9999	-0.33	1	1
HGF/MET/SHIP	-0.023	0.099	-9999	-0.55	10	10

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.015	0.073	-9999	-0.54	2	2
forebrain development	-0.023	0.15	-9999	-0.5	17	17
GNAO1	0.007	0.069	-9999	-0.76	4	4
SMO/beta Arrestin2	0.003	0.087	-9999	-0.42	20	20
SMO	-0.01	0.12	-9999	-0.58	20	20
ARRB2	0.013	0.005	-9999	-10000	0	0
GLI3/SPOP	0.056	0.035	-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	0.027	-9999	-0.49	1	1
GNAI1	0.012	0.026	-9999	-0.57	1	1
XPO1	0.015	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.061	0.11	-9999	-0.48	7	7
SAP30	0.012	0.037	-9999	-0.82	1	1
mol:GDP	-0.01	0.12	-9999	-0.58	20	20
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	0.024	0.067	-9999	-10000	0	0
GLI3	0.051	0.038	-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	0.012	0.037	-9999	-0.82	1	1
Gi family/GTP	0.013	0.089	-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	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.03	0.072	-9999	-10000	0	0
FOXA2	-0.095	0.23	-9999	-0.66	69	69
neural tube patterning	-0.023	0.15	-9999	-0.5	17	17
SPOP	0.014	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.023	0.046	-9999	-0.36	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	0.15	-9999	-0.5	17	17
SUFU	0.019	0.051	-9999	-0.41	1	1
LGALS3	0.011	0.037	-9999	-0.57	2	2
catabolic process	0.063	0.056	-9999	-10000	0	0
GLI3A/CBP	-0.024	0.12	-9999	-10000	0	0
KIF3A	0.014	0	-9999	-10000	0	0
GLI1	-0.024	0.16	-9999	-0.51	17	17
RAB23	0.01	0.053	-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	0.052	-9999	-0.48	1	1
GNAZ	-0.018	0.15	-9999	-0.74	20	20
RBBP4	0.013	0.026	-9999	-0.56	1	1
CSNK1G1	0.014	0	-9999	-10000	0	0
PIAS1	0.014	0	-9999	-10000	0	0
PRKACA	0.014	0	-9999	-10000	0	0
GLI2/SPOP	0.029	0.062	-9999	-10000	0	0
STK36	0.014	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.021	0.08	-9999	-0.43	6	6
PTCH1	-0.02	0.18	-9999	-1.1	6	6
MIM/GLI1	-0.04	0.21	-9999	-0.66	20	20
CREBBP	-0.024	0.12	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.051	0.02	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.053	-9999	-0.54	1	1
BIRC5	-0.023	0.17	-9999	-0.82	22	22
NFKBIA	0.024	0.054	-9999	-0.54	1	1
CPEB1	-0.07	0.22	-9999	-0.63	64	64
AKT1	0.025	0.047	-9999	-10000	0	0
NDEL1	0.014	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.005	0.039	-9999	-10000	0	0
NDEL1/TACC3	-0.006	0.046	-9999	-0.47	2	2
GADD45A	0.012	0.037	-9999	-0.82	1	1
GSK3B	0.013	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.02	0.053	-9999	-0.54	1	1
MDM2	0.014	0	-9999	-10000	0	0
JUB	0.013	0.026	-9999	-0.57	1	1
TPX2	0.013	0.087	-9999	-0.63	9	9
TP53	0.024	0.043	-9999	-0.3	4	4
DLG7	0.014	0.047	-9999	-0.3	10	10
AURKAIP1	0.01	0.053	-9999	-0.82	2	2
ARHGEF7	0.014	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.006	0.049	-9999	-0.49	2	2
G2/M transition of mitotic cell cycle	-0.005	0.039	-9999	-10000	0	0
AURKA	0.017	0.056	-9999	-0.36	10	10
AURKB	-0.007	0.038	-9999	-0.25	10	10
CDC25B	0.012	0.082	-9999	-0.45	4	4
G2/M transition checkpoint	-0.005	0.044	-9999	-0.54	1	1
mRNA polyadenylation	-0.05	0.13	-9999	-0.51	16	16
Aurora A/CPEB	-0.05	0.13	-9999	-0.52	16	16
Aurora A/TACC1/TRAP/chTOG	-0.005	0.039	-9999	-10000	0	0
BRCA1	0.014	0	-9999	-10000	0	0
centrosome duplication	0.02	0.053	-9999	-0.54	1	1
regulation of centrosome cycle	-0.006	0.046	-9999	-0.46	2	2
spindle assembly	-0.005	0.038	-9999	-10000	0	0
TDRD7	0.014	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.025	0.11	-9999	-0.5	22	22
CENPA	-0.007	0.039	-9999	-0.33	5	5
Aurora A/PP2A	0.021	0.046	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.031	0.043	-9999	-10000	0	0
negative regulation of DNA binding	0.024	0.043	-9999	-0.3	4	4
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.011	0.037	-9999	-0.57	2	2
Ajuba/Aurora A	-0.005	0.045	-9999	-0.55	1	1
mitotic prometaphase	0.001	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.056	-9999	-0.35	10	10
TACC1	0.011	0.037	-9999	-0.57	2	2
TACC3	0.01	0.053	-9999	-0.82	2	2
Aurora A/Antizyme1	-0.007	0.049	-9999	-0.5	2	2
Aurora A/RasGAP	0.02	0.052	-9999	-0.34	2	2
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.024	-9999	-0.54	1	1
Importin alpha/Importin beta/TPX2	0.013	0.087	-9999	-0.63	9	9
PPP2R5D	0.014	0	-9999	-10000	0	0
Aurora A/TPX2	0.02	0.085	-9999	-0.52	9	9
PAK1	0.012	0.037	-9999	-0.82	1	1
CKAP5	0.014	0	-9999	-10000	0	0

×

Aurora C signaling

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
INCENP	0.014	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.014	0.086	-9999	-0.52	13	13
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.004	0.022	-9999	-10000	0	0
AURKB	-0.001	0.11	-9999	-0.82	9	9
AURKC	0.005	0.083	-9999	-0.74	6	6

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.035	0.082	-9999	-0.4	9	9
BAG4	0.011	0.037	-9999	-0.57	2	2
BAD	0.029	0.03	-9999	-10000	0	0
NFKBIA	0.012	0.037	-9999	-0.82	1	1
BIRC3	-0.022	0.17	-9999	-0.82	21	21
BAX	0.029	0.03	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.022	-9999	-0.095	9	9
IKBKB	0.042	0.078	-9999	-0.38	5	5
MAP2K2	0.041	0.032	-9999	-10000	0	0
MAP2K1	0.041	0.032	-9999	-10000	0	0
SMPD1	0.018	0.022	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	-0.012	0.17	-9999	-0.65	7	7
MAP2K4	0.036	0.03	-9999	-10000	0	0
protein ubiquitination	0.043	0.079	-9999	-0.38	9	9
EnzymeConsortium:2.7.1.37	0.046	0.035	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.036	0.032	-9999	-10000	0	0
CRADD	0.014	0	-9999	-10000	0	0
mol:ceramide	0.022	0.031	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.001	0.025	-9999	-0.55	1	1
MADD	0.014	0	-9999	-10000	0	0
MAP3K1	0.029	0.031	-9999	-10000	0	0
TRADD	0.014	0	-9999	-10000	0	0
RELA/p50	0.014	0	-9999	-10000	0	0
MAPK3	0.044	0.031	-9999	-10000	0	0
MAPK1	0.044	0.031	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	-0.001	0.028	-9999	-0.63	1	1
FADD	-0.021	0.18	-9999	-0.44	64	64
KSR1	0.029	0.031	-9999	-10000	0	0
MAPK8	0.038	0.044	-9999	-0.3	2	2
TRAF2	0.002	0.098	-9999	-0.82	7	7
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.042	0.078	-9999	-10000	0	0
TNF R/SODD	-0.001	0.026	-9999	-0.41	2	2
TNF	-0.025	0.17	-9999	-0.79	24	24
CYCS	0.032	0.031	-9999	-10000	0	0
IKBKG	0.042	0.078	-9999	-0.38	5	5
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.085	-9999	-0.43	9	9
RELA	0.014	0	-9999	-10000	0	0
RIPK1	0.014	0	-9999	-10000	0	0
AIFM1	0.032	0.031	-9999	-10000	0	0
TNF/TNF R/SODD	-0.026	0.11	-9999	-0.54	21	21
TNFRSF1A	0.014	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.022	-9999	-10000	0	0
NSMAF	0.035	0.081	-9999	-0.4	9	9
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.002	0.09	-9999	-0.69	8	8

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.017	0.13	-9999	-0.57	26	26
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.019	0.045	-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	0.037	-9999	-0.82	1	1
MAP3K12	0.011	0.045	-9999	-0.69	2	2
FGR	0.012	0.037	-9999	-0.82	1	1
p38 alpha/TAB1	-0.018	0.04	-9999	-10000	0	0
PRKG1	-0.021	0.15	-9999	-0.65	26	26
DUSP8	0.014	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.031	0.076	-9999	-0.39	13	13
apoptosis	-0.017	0.039	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.012	0.037	-9999	-0.82	1	1
DUSP1	-0.015	0.13	-9999	-0.57	25	25
PAK1	0.012	0.037	-9999	-0.82	1	1
SRC	0.014	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.01	0.067	-9999	-0.49	9	9
TRAF6	0.014	0	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	-0.001	0.11	-9999	-0.82	9	9
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.024	0.093	-9999	-0.37	4	4
BLK	-0.1	0.28	-9999	-0.78	71	71
HCK	0.006	0.079	-9999	-0.77	5	5
MAP2K3	0.013	0.026	-9999	-0.57	1	1
DUSP16	0.014	0	-9999	-10000	0	0
DUSP10	0.012	0.037	-9999	-0.82	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.032	0.067	-9999	-10000	0	0
positive regulation of innate immune response	0.032	0.1	-9999	-0.4	1	1
LCK	-0.006	0.13	-9999	-0.82	12	12
p38alpha-beta/MKP7	0.037	0.096	-9999	-10000	0	0
p38alpha-beta/MKP5	0.036	0.098	-9999	-10000	0	0
PGK/cGMP	-0.026	0.11	-9999	-0.49	26	26
PAK2	0.014	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.024	0.12	-9999	-0.5	3	3
CDC42	0.014	0	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
PAK3	-0.018	0.15	-9999	-0.82	17	17

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.029	-9999	-10000	0	0
DAPP1	0.015	0.091	-9999	-0.37	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.001	0.16	-9999	-0.65	15	15
mol:DAG	0.029	0.087	-9999	-0.3	9	9
HRAS	0.013	0.037	-9999	-0.82	1	1
RAP1A	0.014	0.002	-9999	-10000	0	0
ARF5/GDP	0.04	0.041	-9999	-0.3	1	1
PLCG2	0.013	0.026	-9999	-0.57	1	1
PLCG1	0.014	0	-9999	-10000	0	0
ARF5	0.014	0	-9999	-10000	0	0
mol:GTP	-0.002	0.031	-9999	-0.41	3	3
ARF1/GTP	-0.002	0.028	-9999	-10000	0	0
RHOA	0.014	0	-9999	-10000	0	0
YES1	0.014	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.031	-9999	-0.4	3	3
ADAP1	-0.003	0.032	-9999	-10000	0	0
ARAP3	-0.002	0.031	-9999	-0.4	3	3
INPPL1	0.014	0	-9999	-10000	0	0
PREX1	0.014	0	-9999	-10000	0	0
ARHGEF6	0.008	0.058	-9999	-0.57	5	5
ARHGEF7	0.014	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
NRAS	0.015	0.002	-9999	-10000	0	0
FYN	0.012	0.037	-9999	-0.82	1	1
ARF6	0.014	0	-9999	-10000	0	0
FGR	0.012	0.037	-9999	-0.82	1	1
mol:Ca2+	0.027	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.007	0.063	-9999	-0.57	6	6
ZAP70	-0.026	0.17	-9999	-0.78	25	25
mol:IP3	0.031	0.063	-9999	-10000	0	0
LYN	0.012	0.037	-9999	-0.82	1	1
ARF1/GDP	0.04	0.041	-9999	-10000	0	0
RhoA/GDP	-0.003	0.029	-9999	-0.42	1	1
PDK1/Src/Hsp90	-0.001	0.015	-9999	-10000	0	0
BLNK	-0.042	0.17	-9999	-0.57	48	48
actin cytoskeleton reorganization	0.062	0.044	-9999	-0.41	1	1
SRC	0.014	0	-9999	-10000	0	0
PLEKHA2	0.03	0.028	-9999	-10000	0	0
RAC1	0.014	0	-9999	-10000	0	0
PTEN	0	0.004	-9999	-10000	0	0
HSP90AA1	0.014	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.029	-9999	-10000	0	0
RhoA/GTP	-0.002	0.029	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.018	0.17	-9999	-0.69	17	17
BLK	-0.1	0.28	-9999	-0.78	71	71
PDPK1	0.013	0.026	-9999	-0.57	1	1
CYTH1	-0.002	0.029	-9999	-10000	0	0
HCK	0.006	0.079	-9999	-0.77	5	5
CYTH3	-0.002	0.029	-9999	-10000	0	0
CYTH2	-0.002	0.029	-9999	-10000	0	0
KRAS	0.011	0.053	-9999	-0.82	2	2
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.004	0.034	-9999	-0.44	2	2
SGK1	-0.004	0.037	-9999	-0.48	2	2
INPP5D	0.01	0.045	-9999	-0.57	3	3
mol:GDP	0.034	0.043	-9999	-0.32	1	1
SOS1	0.014	0	-9999	-10000	0	0
SYK	0.01	0.045	-9999	-0.57	3	3
ARF6/GDP	-0.003	0.029	-9999	-0.42	1	1
mol:PI-3-4-5-P3	-0.002	0.031	-9999	-0.41	3	3
ARAP3/RAP1A/GTP	-0.002	0.031	-9999	-0.41	3	3
VAV1	0.003	0.082	-9999	-0.59	9	9
mol:PI-3-4-P2	0.022	0.033	-9999	-0.41	3	3
RAS family/GTP/PI3K Class I	0.031	0.035	-9999	-0.42	3	3
PLEKHA1	0.03	0.028	-9999	-10000	0	0
Rac1/GDP	0.04	0.041	-9999	-10000	0	0
LAT	-0.011	0.14	-9999	-0.82	15	15
Rac1/GTP	0.035	0.055	-9999	-0.34	1	1
ITK	-0.014	0.07	-9999	-0.43	8	8
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.028	0.11	-9999	-0.45	9	9
LCK	-0.006	0.13	-9999	-0.82	12	12
BTK	-0.004	0.04	-9999	-0.43	2	2

×

Arf6 trafficking 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.25	0.29	-10000	0	-0.57	223	223
CLTC	0.034	0.014	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.028	0.013	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.022	-10000	0	-0.5	1	1
EXOC4	0.014	0	-10000	0	-10000	0	0
CD59	0.03	0.01	-10000	0	-10000	0	0
CPE	0.013	0.063	-10000	0	-0.55	6	6
CTNNB1	0.013	0.026	-10000	0	-0.57	1	1
membrane fusion	0.027	0.014	-10000	0	-10000	0	0
CTNND1	0.033	0.022	-10000	0	-0.46	1	1
DNM2	0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.034	0.009	-10000	0	-10000	0	0
TSHR	0.001	0.098	-10000	0	-0.55	15	15
INS	0.012	0.017	-10000	0	-0.26	2	2
BIN1	0	0.1	-10000	0	-0.76	9	9
mol:Choline	0.027	0.014	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.026	-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	0.022	-10000	0	-0.5	1	1
JUP	0.03	0.02	-10000	0	-0.28	1	1
ASAP2/amphiphysin II	-0.008	0.062	-10000	0	-0.5	7	7
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.028	0.026	-10000	0	-0.28	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.025	0.39	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	0.025	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.039	0.015	-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	0.022	-10000	0	-0.46	1	1
NME1	0.019	0.026	-10000	0	-0.55	1	1
clathrin coat assembly	0.034	0.014	-10000	0	-10000	0	0
IL2RA	0.007	0.074	-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	-0.4	3	3
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.002	0.021	-10000	0	-0.28	3	3
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0.009	-10000	0	-10000	0	0
SDC1	0.03	0.01	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.025	-10000	0	-0.55	1	1
EXOC7	0.014	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.003	0.025	-10000	0	-0.4	1	1
mol:Phosphatidic acid	0.027	0.014	-10000	0	-10000	0	0
endocytosis	0.008	0.062	0.5	7	-10000	0	7
SCAMP2	0.014	0	-10000	0	-10000	0	0
ADRB2	0.019	0.08	-10000	0	-0.53	1	1
EXOC3	0.014	0	-10000	0	-10000	0	0
ASAP2	0.014	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.026	0.023	-10000	0	-0.5	1	1
KLC1	0.014	0	-10000	0	-10000	0	0
AVPR2	0.024	0.068	-10000	0	-10000	0	0
RALA	0.014	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.023	-10000	0	-10000	0	0

×

PLK1 signaling events

Figure 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
regulation of centriole-centriole cohesion	-0.011	0.007	-10000	0	-10000	0	0
BUB1B	0.022	0.025	-10000	0	-10000	0	0
PLK1	0.017	0.022	-10000	0	-0.17	1	1
PLK1S1	0.015	0.014	-10000	0	-0.17	1	1
KIF2A	0.024	0.019	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.017	0.022	-10000	0	-0.17	1	1
GOLGA2	0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.01	0.1	-10000	0	-0.48	21	21
WEE1	0.022	0.027	-10000	0	-10000	0	0
cytokinesis	0.03	0.033	-10000	0	-10000	0	0
PP2A-alpha B56	0.036	0.013	-10000	0	-10000	0	0
AURKA	0.012	0.032	-10000	0	-0.18	11	11
PICH/PLK1	0.023	0.085	-10000	0	-0.39	20	20
CENPE	0.024	0.019	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.024	0.019	-10000	0	-10000	0	0
PPP2CA	0.014	0	-10000	0	-10000	0	0
FZR1	0.014	0	-10000	0	-10000	0	0
TPX2	0.012	0.028	-10000	0	-0.18	9	9
PAK1	0.012	0.037	-10000	0	-0.81	1	1
SPC24	-0.006	0.13	-10000	0	-0.82	12	12
FBXW11	0.014	0	-10000	0	-10000	0	0
CLSPN	0.012	0.033	-10000	0	-0.21	9	9
GORASP1	0.014	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.015	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.009	0.011	-10000	0	-0.067	5	5
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.013	11	11
STAG2	0.014	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.009	-10000	0	-10000	0	0
spindle elongation	0.017	0.022	-10000	0	-0.17	1	1
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	-0.001	0.01	-10000	0	-10000	0	0
TPT1	0.015	0.011	-10000	0	-10000	0	0
CDC25C	0.011	0.042	-10000	0	-0.26	11	11
CDC25B	-0.019	0.16	-10000	0	-0.81	20	20
SGOL1	0.011	0.007	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.017	0.078	-10000	0	-0.4	20	20
CDC14B	0.009	0.034	-10000	0	-0.42	3	3
CDC20	0	0.1	-10000	0	-0.82	8	8
PLK1/PBIP1	-0.004	0.033	-10000	0	-0.49	2	2
mitosis	0.001	0.007	0.041	11	-10000	0	11
FBXO5	0.021	0.02	-10000	0	-10000	0	0
CDC2	0.001	0.004	-10000	0	-0.017	20	20
NDC80	-0.001	0.11	-10000	0	-0.82	9	9
metaphase plate congression	0.016	0.012	-10000	0	-10000	0	0
ERCC6L	-0.015	0.073	-10000	0	-0.37	20	20
NLP/gamma Tubulin	0.014	0.012	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.015	0.011	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-0.011	4	4
PPP1R12A	0.014	0.001	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-0.011	4	4
PLK1/PRC1-2	0.031	0.018	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.01	-10000	0	-10000	0	0
RAB1A	0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.016	0.049	-10000	0	-0.47	4	4
mitotic prometaphase	0	0.001	-10000	0	-0.01	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.031	-10000	0	-0.38	1	1
microtubule-based process	0.023	0.019	-10000	0	-10000	0	0
Golgi organization	0.017	0.022	-10000	0	-0.17	1	1
Cohesin/SA2	-0.002	0.012	-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	0.015	0.072	-10000	0	-0.53	8	8
PPP2R1A	0.014	0	-10000	0	-10000	0	0
chromosome segregation	-0.004	0.033	-10000	0	-0.48	2	2
PRC1	0.014	0	-10000	0	-10000	0	0
ECT2	0.019	0.055	-10000	0	-0.49	5	5
C13orf34	0.017	0.048	-10000	0	-0.48	4	4
NUDC	0.016	0.013	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.022	0.024	-10000	0	-10000	0	0
spindle assembly	0.017	0.017	-10000	0	-0.12	1	1
spindle stabilization	0.015	0.014	-10000	0	-0.17	1	1
APC/C/HCDH1	0.017	0.029	-10000	0	-0.35	3	3
MKLP2/PLK1	0.023	0.019	-10000	0	-10000	0	0
CCNB1	0.014	0.003	-10000	0	-10000	0	0
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.014	0	-10000	0	-10000	0	0
ROCK2	0.016	0.061	-10000	0	-0.42	9	9
TUBG1	0.015	0.011	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.016	0.077	-10000	0	-0.39	20	20
MLF1IP	0.01	0.042	-10000	0	-0.65	2	2
INCENP	0.014	0.001	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0	-10000	0	-10000	0	0
NFATC1	0.061	0.018	-10000	0	-10000	0	0
NFATC2	0.024	0.063	-10000	0	-0.35	5	5
NFATC3	0.025	0.019	-10000	0	-0.39	1	1
YWHAE	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.077	-10000	0	-0.38	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.039	0.1	-10000	0	-0.57	7	7
BCL2/BAX	-0.008	0.067	-10000	0	-0.52	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.002	-10000	0	-10000	0	0
CaM/Ca2+	0.012	0.002	-10000	0	-10000	0	0
BAX	0.014	0	-10000	0	-10000	0	0
MAPK14	0.014	0.002	-10000	0	-10000	0	0
BAD	0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.018	0.072	-10000	0	-0.37	2	2
Calcineurin A alpha-beta B1/BCL2	0.002	0.09	-10000	0	-0.69	8	8
FKBP8	0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.018	0.071	0.37	2	-10000	0	2
KPNB1	0.014	0	-10000	0	-10000	0	0
KPNA2	0.014	0	-10000	0	-10000	0	0
XPO1	0.014	0	-10000	0	-10000	0	0
SFN	0.006	0.074	-10000	0	-0.72	5	5
MAP3K8	0.011	0.045	-10000	0	-0.57	3	3
NFAT4/CK1 alpha	0	0.01	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.015	0.053	-10000	0	-10000	0	0
CABIN1	0.011	0.077	-10000	0	-0.39	4	4
CALM1	0.014	0.002	-10000	0	-10000	0	0
RAN	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.014	0	-10000	0	-10000	0	0
CAMK4	-0.031	0.18	-10000	0	-0.78	28	28
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.014	0	-10000	0	-10000	0	0
YWHAH	0.014	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.032	0.14	-10000	0	-0.63	25	25
YWHAB	0.014	0	-10000	0	-10000	0	0
MAPK8	0.006	0.068	-10000	0	-0.57	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	0.026	-10000	0	-0.4	2	2
CASP3	0.014	0.002	-10000	0	-10000	0	0
PIM1	0.013	0.026	-10000	0	-0.57	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.021	-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	0.1	-10000	0	-0.79	8	8
PRKCE	0.013	0.026	-10000	0	-0.57	1	1
JNK2/NFAT4	0.03	0.017	-10000	0	-0.35	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.014	0	-10000	0	-10000	0	0
NUP214	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.013	0.026	-10000	0	-0.57	1	1
PRKCA	0.011	0.045	-10000	0	-0.69	2	2
PRKCG	-0.082	0.26	-10000	0	-0.82	55	55
PRKCQ	0	0.093	-10000	0	-0.61	11	11
FKBP38/BCL2	-0.008	0.067	-10000	0	-0.52	8	8
EP300	0.012	0.037	-10000	0	-0.56	2	2
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	0.062	0.038	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.022	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.029	0.12	-10000	0	-0.52	28	28
NFATc/ERK1	0.066	0.017	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.039	0.1	-10000	0	-0.57	7	7
NR4A1	0.049	0.096	-10000	0	-0.55	9	9
GSK3B	0.014	0.002	-10000	0	-10000	0	0
positive T cell selection	0.025	0.019	-10000	0	-0.39	1	1
NFAT1/CK1 alpha	-0.012	0.037	-10000	0	-0.36	2	2
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.014	0	-10000	0	-10000	0	0
PRKACA	0.014	0.002	-10000	0	-10000	0	0
AKAP5	-0.028	0.18	-10000	0	-0.82	25	25
MEF2D	0.014	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.066	0.019	-10000	0	-10000	0	0
CREBBP	0.014	0.002	-10000	0	-10000	0	0
BCL2	0.002	0.09	-10000	0	-0.69	8	8

×

TCGA08_rtk_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
PDGFRA	0.002	0.086	-9999	-0.62	9	9
HRAS	0.012	0.037	-9999	-0.82	1	1
EGFR	-0.017	0.15	-9999	-0.76	20	20
AKT	0.037	0.049	-9999	-0.3	9	9
FOXO3	0.014	0	-9999	-10000	0	0
AKT1	0.014	0	-9999	-10000	0	0
FOXO1	0.014	0	-9999	-10000	0	0
AKT3	-0.001	0.11	-9999	-0.82	9	9
FOXO4	0.011	0.037	-9999	-0.57	2	2
MET	0.005	0.083	-9999	-0.74	6	6
PIK3CA	0.014	0	-9999	-10000	0	0
PIK3CB	0.014	0	-9999	-10000	0	0
NRAS	0.014	0	-9999	-10000	0	0
PIK3CG	-0.019	0.16	-9999	-0.76	21	21
PIK3R3	0.014	0	-9999	-10000	0	0
PIK3R2	0.014	0	-9999	-10000	0	0
NF1	0.014	0	-9999	-10000	0	0
RAS	0.016	0.048	-9999	-0.34	1	1
ERBB2	0.009	0.064	-9999	-0.82	3	3
proliferation/survival/translation	-0.031	0.026	-9999	-10000	0	0
PI3K	0.024	0.052	-9999	-0.26	3	3
PIK3R1	0.01	0.045	-9999	-0.57	3	3
KRAS	0.01	0.053	-9999	-0.82	2	2
FOXO	0.048	0.029	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0

×

E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.005	0.051	-9999	-0.66	2	2
E-cadherin/beta catenin	-0.005	0.044	-9999	-0.41	6	6
CTNNB1	0.013	0.026	-9999	-0.57	1	1
JUP	0.011	0.037	-9999	-0.57	2	2
CDH1	0.008	0.058	-9999	-0.57	5	5

×

Canonical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.086	0.033	-9999	-10000	0	0
ERC1	0.014	0	-9999	-10000	0	0
RIP2/NOD2	-0.005	0.051	-9999	-0.5	5	5
NFKBIA	0.048	0.036	-9999	-0.76	1	1
BIRC2	-0.005	0.12	-9999	-0.82	11	11
IKBKB	0.014	0	-9999	-10000	0	0
RIPK2	0.014	0	-9999	-10000	0	0
IKBKG	-0.006	0.033	-9999	-10000	0	0
IKK complex/A20	-0.022	0.086	-9999	-0.58	2	2
NEMO/A20/RIP2	0.014	0	-9999	-10000	0	0
XPO1	0.014	0	-9999	-10000	0	0
NEMO/ATM	0.047	0.042	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.025	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.007	0.069	-9999	-0.67	5	5
NFKB1	0.017	0.006	-9999	-10000	0	0
RELA	0.017	0.006	-9999	-10000	0	0
MALT1	0.014	0	-9999	-10000	0	0
cIAP1/UbcH5C	-0.014	0.092	-9999	-0.63	11	11
ATM	0.013	0.026	-9999	-0.57	1	1
TNF/TNFR1A	-0.029	0.13	-9999	-0.6	24	24
TRAF6	0.014	0	-9999	-10000	0	0
PRKCA	0.011	0.045	-9999	-0.69	2	2
CHUK	0.014	0	-9999	-10000	0	0
UBE2D3	0.014	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.79	24	24
NF kappa B1 p50/RelA	-0.001	0.015	-9999	-10000	0	0
BCL10	0.014	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.036	-9999	-0.75	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0.006	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
IKK complex	0.054	0.039	-9999	-10000	0	0
CYLD	0.014	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.036	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.022	-9999	-0.49	1	1
HDAC3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.001	0.028	-9999	-0.63	1	1
GATA1/HDAC5	-0.001	0.028	-9999	-0.63	1	1
GATA2/HDAC5	-0.006	0.059	-9999	-0.58	5	5
HDAC5/BCL6/BCoR	-0.001	0.015	-9999	-10000	0	0
HDAC9	-0.035	0.2	-9999	-0.82	29	29
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.006	0.079	-9999	-0.77	5	5
HDAC4/RFXANK	-0.001	0.028	-9999	-0.63	1	1
BCOR	0.013	0.026	-9999	-0.57	1	1
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0	-9999	-10000	0	0
HDAC5	0.014	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.028	-9999	-0.63	1	1
Histones	0.029	0.057	-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	0.028	-9999	-0.63	1	1
CAMK4	-0.031	0.18	-9999	-0.78	28	28
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	0.038	-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	-0.001	0.018	-9999	-0.41	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.029	0.12	-9999	-0.54	24	24
HDAC4/ER alpha	-0.032	0.13	-9999	-0.52	31	31
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.057	-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	-0.7	31	31
HDAC6/HDAC11	-0.001	0.018	-9999	-0.41	1	1
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0	0.1	-9999	-0.69	10	10
RAN	0.014	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.007	0.053	-9999	-0.46	5	5
GNG2	0.012	0.037	-9999	-0.82	1	1
NCOR2	0.014	0	-9999	-10000	0	0
TUBB2A	0.014	0	-9999	-10000	0	0
HDAC11	0.013	0.026	-9999	-0.57	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	0.037	-9999	-0.82	1	1
nuclear import	-0.031	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.011	0.048	0.43	2	-10000	0	2
GNAI2	0.014	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.006	0.054	-10000	0	-0.48	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.008	0.069	-10000	0	-0.76	4	4
RhoA/GTP	-0.011	0.049	-10000	0	-0.44	2	2
negative regulation of cAMP metabolic process	0.023	0.063	-10000	0	-0.48	2	2
GNAZ	-0.017	0.15	-10000	0	-0.74	20	20
GNAI3	0.014	0	-10000	0	-10000	0	0
GNA12	0.01	0.053	-10000	0	-0.82	2	2
S1PR5	0.008	0.064	-10000	0	-0.69	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.023	0.064	-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	0.013	0.026	-10000	0	-0.57	1	1

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.049	0.04	-10000	0	-10000	0	0
adherens junction organization	0.037	0.057	-10000	0	-0.63	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.039	0.088	-10000	0	-0.59	1	1
FMN1	0.022	0.093	-10000	0	-0.64	3	3
mol:IP3	0.041	0.038	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.035	0.049	-10000	0	-0.6	2	2
CTNNB1	0.012	0.026	-10000	0	-0.56	1	1
AKT1	0.047	0.04	-10000	0	-0.41	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.059	-10000	0	-0.64	2	2
CTNND1	0.015	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.042	0.046	-10000	0	-0.55	2	2
VASP	0.042	0.047	-10000	0	-0.57	2	2
ZYX	0.042	0.047	-10000	0	-0.57	2	2
JUB	0.042	0.048	-10000	0	-0.57	2	2
EGFR(dimer)	0.024	0.1	-10000	0	-0.46	17	17
E-cadherin/beta catenin-gamma catenin	-0.005	0.049	-10000	0	-0.62	2	2
mol:PI-3-4-5-P3	-0.005	0.036	-10000	0	-0.44	2	2
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
PI3K	-0.005	0.037	-10000	0	-0.45	2	2
FYN	0.046	0.061	-10000	0	-0.57	1	1
mol:Ca2+	0.04	0.037	-10000	0	-10000	0	0
JUP	0.011	0.036	-10000	0	-0.56	2	2
PIK3R1	0.011	0.045	-10000	0	-0.57	3	3
mol:DAG	0.041	0.038	-10000	0	-10000	0	0
CDH1	0.008	0.058	-10000	0	-0.56	5	5
RhoA/GDP	0.039	0.088	-10000	0	-0.59	1	1
establishment of polarity of embryonic epithelium	0.042	0.046	-10000	0	-0.55	2	2
SRC	0.014	0	-10000	0	-10000	0	0
RAC1	0.014	0	-10000	0	-10000	0	0
RHOA	0.014	0	-10000	0	-10000	0	0
EGFR	-0.017	0.15	-10000	0	-0.76	20	20
CASR	0.037	0.068	-10000	0	-0.41	8	8
RhoA/GTP	-0.003	0.028	-10000	0	-10000	0	0
AKT2	0.047	0.04	-10000	0	-0.41	2	2
actin cable formation	0.029	0.09	-10000	0	-0.61	3	3
apoptosis	0.004	0.034	0.4	2	-10000	0	2
CTNNA1	0.015	0.002	-10000	0	-10000	0	0
mol:GDP	0.033	0.093	-10000	0	-0.65	1	1
PIP5K1A	0.042	0.047	-10000	0	-0.57	2	2
PLCG1	-0.004	0.033	-10000	0	-10000	0	0
Rac1/GTP	-0.018	0.082	-10000	0	-0.63	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Alternative 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
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	-0.006	0.05	-9999	-0.46	6	6
NFKB1	0.014	0	-9999	-10000	0	0
MAP3K14	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.008	0.069	-9999	-0.63	6	6
RELB	0.004	0.091	-9999	-0.82	6	6
NFKB2	0.014	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.007	0.06	-9999	-0.55	6	6
regulation of B cell activation	-0.007	0.06	-9999	-0.55	6	6

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0.026	-9999	-0.57	1	1
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.044	0.011	-9999	-10000	0	0
SMAD3/SMAD4	0.05	0.012	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.015	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0.011	-9999	-10000	0	0
PPM1A	0.014	0	-9999	-10000	0	0
CALM1	0.014	0	-9999	-10000	0	0
SMAD2/SMAD4	0.022	0.014	-9999	-0.3	1	1
MAP3K1	0.014	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.015	0.076	-9999	-0.41	18	18
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	0.1	-9999	-0.57	17	17
UBE2I	0.014	0	-9999	-10000	0	0
NUP153	0.014	0	-9999	-10000	0	0
KPNA2	0.014	0	-9999	-10000	0	0
PIAS4	0.014	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

Figure 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
PLK2	0.011	0.037	-9999	-0.57	2	2
PLK4	0.014	0	-9999	-10000	0	0
regulation of centriole replication	0.023	0.027	-9999	-0.41	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.076	0.086	-10000	0	-0.38	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	0.3	7	-0.43	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	-0.011	0.13	-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	0.013	0.026	-10000	0	-0.57	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	7	-0.48	1	8
STX4	0.014	0	-10000	0	-10000	0	0
GSK3B	0.028	0	-10000	0	-10000	0	0
SFN	0.006	0.074	-10000	0	-0.72	5	5
LNPEP	0.011	0.037	-10000	0	-0.57	2	2
YWHAE	0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.02	0.086	-9999	-0.41	21	21
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.076	-9999	-10000	0	0
SUMO1	0.014	0	-9999	-10000	0	0
ZFPM1	0.014	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	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	0.062	-9999	-0.6	1	1
SMG5	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.02	0.074	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.022	0.055	-9999	-0.34	1	1
SAP18	0.014	0	-9999	-10000	0	0
RELA	0.026	0.064	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.014	0	-9999	-10000	0	0
HDAC3/TR2	0.023	0.052	-9999	-10000	0	0
NuRD/MBD3 Complex	0.051	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.058	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.006	0.079	-9999	-0.77	5	5
GATA1	0.009	0.038	-9999	-0.82	1	1
Mad/Max	-0.004	0.04	-9999	-0.41	5	5
NuRD/MBD3 Complex/GATA1/Fog1	0.061	0.014	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.013	0.026	-9999	-0.57	1	1
MAX	0.014	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.014	0	-9999	-10000	0	0
NFKBIA	0.017	0.061	-9999	-0.39	1	1
KAT2B	-0.014	0.12	-9999	-0.57	24	24
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.046	0.015	-9999	-10000	0	0
SIN3 complex	-0.001	0.022	-9999	-0.49	1	1
SMURF1	0.014	0	-9999	-10000	0	0
CHD3	0.014	0	-9999	-10000	0	0
SAP30	0.012	0.037	-9999	-0.82	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.014	0	-9999	-10000	0	0
YY1/HDAC3	0.024	0.071	-9999	-0.52	1	1
YY1/HDAC2	0.019	0.062	-9999	-0.6	1	1
YY1/HDAC1	0.019	0.062	-9999	-0.6	1	1
NuRD/MBD2 Complex (MeCP1)	0.051	0.009	-9999	-10000	0	0
PPARG	-0.13	0.16	-9999	-0.46	21	21
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.014	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.014	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.023	0.052	-9999	-10000	0	0
MBD3L2	-0.003	0.052	-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	0.054	0.017	-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	0.073	-9999	-0.67	1	1
HDAC8	0.014	0	-9999	-10000	0	0
SMAD7	0.014	0	-9999	-10000	0	0
NCOR2	0.014	0	-9999	-10000	0	0
MXD1	0.008	0.058	-9999	-0.57	5	5
STAT3	0.026	0.023	-9999	-0.33	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	0.049	-9999	-0.55	1	1
YY1/SAP30/HDAC1	-0.012	0.057	-9999	-0.62	2	2
EP300	0.011	0.037	-9999	-0.57	2	2
STAT3 (dimer non-phopshorylated)	0.026	0.023	-9999	-0.33	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.061	-9999	-0.39	1	1
histone deacetylation	0.051	0.009	-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	0.018	0.074	-9999	-0.55	4	4
GATA1/HDAC1	-0.001	0.028	-9999	-0.63	1	1
GATA1/HDAC3	0.016	0.058	-9999	-0.49	1	1
CHD4	0.014	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.029	0.13	-9999	-0.6	24	24
SIN3/HDAC complex/Mad/Max	0.049	0.024	-9999	-10000	0	0
NuRD Complex	0.06	0.01	-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	0.013	-9999	-10000	0	0
GATA1/Fog1	-0.001	0.028	-9999	-0.63	1	1
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.025	0.17	-9999	-0.79	24	24
negative regulation of cell growth	0.048	0.024	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.051	0.009	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.027	0.079	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.048	0.014	-9999	-10000	0	0
TFCP2	0.014	0	-9999	-10000	0	0
NR2C1	0.014	0	-9999	-10000	0	0
MBD3	0.014	0	-9999	-10000	0	0
MBD2	0.014	0	-9999	-10000	0	0

×

FoxO family signaling

Figure 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
G6PC	0.039	0.045	-9999	-0.62	2	2
PLK1	0.11	0.11	-9999	-0.92	2	2
CDKN1B	0.15	0.054	-9999	-10000	0	0
FOXO3	0.11	0.11	-9999	-0.88	1	1
KAT2B	-0.002	0.13	-9999	-0.56	24	24
FOXO1/SIRT1	0.009	0.034	-9999	-10000	0	0
CAT	0.11	0.12	-9999	-0.98	2	2
CTNNB1	0.012	0.026	-9999	-0.57	1	1
AKT1	0.029	0.011	-9999	-10000	0	0
FOXO1	0.043	0.025	-9999	-10000	0	0
MAPK10	0.026	0.082	-9999	-0.46	4	4
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.1	0.051	-9999	-10000	0	0
response to oxidative stress	0.017	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	0.005	0.078	-9999	-0.7	2	2
XPO1	0.015	0	-9999	-10000	0	0
EP300	0.013	0.037	-9999	-0.57	2	2
BCL2L11	0.042	0.026	-9999	-10000	0	0
FOXO1/SKP2	0.043	0.032	-9999	-0.47	1	1
mol:GDP	0.017	0.011	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
GADD45A	0.13	0.054	-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	0.017	0.084	-9999	-0.72	6	6
CSNK1D	0.014	0	-9999	-10000	0	0
CSNK1E	0.014	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.062	0.028	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
MAPK8	0.041	0.038	-9999	-10000	0	0
MAPK9	0.045	0.005	-9999	-10000	0	0
YWHAG	0.014	0	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
SIRT1	0.006	0.031	-9999	-0.56	1	1
SOD2	0.16	0.061	-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	-0.033	0.28	-9999	-0.85	45	45
SKP2	0.012	0.037	-9999	-0.82	1	1
USP7	0.016	0	-9999	-10000	0	0
IKBKB	0.026	0.009	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.79	1	1
FOXO1-3a-4/beta catenin	0.12	0.099	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.043	0.032	-9999	-0.47	1	1
CSNK1A1	0.014	0	-9999	-10000	0	0
SGK1	0.022	0.053	-9999	-0.64	3	3
CSNK1G3	0.014	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0.001	-9999	-10000	0	0
ZFAND5	0.11	0.046	-9999	-10000	0	0
SFN	0.006	0.074	-9999	-0.72	5	5
CDK2	0.014	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.076	0.036	-9999	-10000	0	0
CREBBP	0.014	0.005	-9999	-10000	0	0
FBXO32	0.1	0.14	-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 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
BCL3/RelA	-0.001	0.018	-9999	-0.41	1	1
FBXW11	0.014	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.022	0.049	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.045	0.041	-9999	-0.45	1	1
NFKBIA	0.024	0.047	-9999	-0.52	1	1
MAPK14	0.014	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.028	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	0.003	0.077	-9999	-0.57	9	9
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.028	0.016	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0	-9999	-10000	0	0
PIK3CA	0.014	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.022	0	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	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	0.042	-9999	-0.41	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.048	0.041	-9999	-0.43	1	1
SRC	0.014	0	-9999	-10000	0	0
PI3K	-0.002	0.031	-9999	-0.41	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	0.01	0.045	-9999	-0.57	3	3
I kappa B alpha/PIK3R1	0.028	0.05	-9999	-0.49	1	1
cell death	0.046	0.039	-9999	-0.41	1	1
NF kappa B1 p105/c-Rel	0.022	0.049	-9999	-10000	0	0
LCK	-0.006	0.13	-9999	-0.82	12	12
BCL3	0.013	0.026	-9999	-0.57	1	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.029	0.084	-9999	-0.43	16	16
KLHL20	-0.01	0.038	-9999	-0.3	2	2
CYFIP2	0.01	0.052	-9999	-0.65	3	3
Rac1/GDP	0.06	0.038	-9999	-10000	0	0
ENAH	0.038	0.06	-9999	-0.49	6	6
AP1M1	0.014	0	-9999	-10000	0	0
RAP1B	0.012	0.037	-9999	-0.82	1	1
RAP1A	0.014	0	-9999	-10000	0	0
CTNNB1	0.013	0.026	-9999	-0.57	1	1
CDC42/GTP	-0.003	0.024	-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	0.038	-9999	-10000	0	0
RAPGEF1	0.053	0.048	-9999	-10000	0	0
CTNND1	0.014	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.006	0.051	-9999	-0.46	6	6
CRK	0.047	0.051	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	-0.005	0.049	-9999	-0.66	2	2
alphaE/beta7 Integrin	-0.002	0.026	-9999	-0.41	2	2
IQGAP1	0.014	0	-9999	-10000	0	0
NCKAP1	0.012	0.037	-9999	-0.82	1	1
Rap1/GTP/I-afadin	-0.001	0.022	-9999	-0.5	1	1
DLG1	0.039	0.054	-9999	-0.44	6	6
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.019	-9999	-10000	0	0
MLLT4	0.014	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.005	0.04	-9999	-0.5	1	1
PI3K	-0.003	0.024	-9999	-10000	0	0
ARF6	0.014	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.005	0.057	-9999	-0.54	5	5
TIAM1	0.007	0.063	-9999	-0.57	6	6
E-cadherin(dimer)/Ca2+	-0.003	0.031	-9999	-10000	0	0
AKT1	-0.002	0.014	-9999	-10000	0	0
PIK3R1	0.01	0.045	-9999	-0.57	3	3
CDH1	0.008	0.058	-9999	-0.57	5	5
RhoA/GDP	0.059	0.038	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.028	-9999	-0.22	2	2
CDC42/GDP	0.059	0.038	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.023	0.04	-9999	-0.51	2	2
ITGB7	0.011	0.037	-9999	-0.57	2	2
RAC1	0.014	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.004	0.033	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.003	0.032	-9999	-10000	0	0
mol:GDP	0.056	0.043	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.037	-9999	-0.57	2	2
p120 catenin/RhoA/GDP	-0.004	0.028	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.014	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	0.048	-9999	-0.25	12	12
NME1	0.012	0.037	-9999	-0.82	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.039	0.054	-9999	-0.44	6	6
regulation of cell-cell adhesion	-0.002	0.021	-9999	-10000	0	0
WASF2	-0.004	0.014	-9999	-10000	0	0
Rap1/GTP	-0.003	0.027	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.045	-9999	-0.57	2	2
CCND1	0.033	0.059	-9999	-0.32	12	12
VAV2	0.041	0.073	-9999	-10000	0	0
RAP1/GDP	-0.001	0.03	-9999	-10000	0	0
adherens junction assembly	0.039	0.052	-9999	-0.43	6	6
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	-0.005	0.044	-9999	-0.54	2	2
E-cadherin/beta catenin	-0.004	0.037	-9999	-0.37	5	5
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.039	0.054	-9999	-0.45	6	6
PIK3CA	0.014	0	-9999	-10000	0	0
Rac1/GTP	-0.016	0.061	-9999	-0.53	2	2
E-cadherin/beta catenin/alpha catenin	-0.004	0.037	-9999	-10000	0	0
ITGAE	0.014	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.052	-9999	-0.48	6	6

×

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	0.03	-10000	0	-10000	0	0
FRAP1	0.015	0.01	-10000	0	-10000	0	0
AKT1	0.027	0.031	-10000	0	-10000	0	0
INSR	0.013	0.026	-10000	0	-0.57	1	1
Insulin Receptor/Insulin	-0.003	0.038	-10000	0	-0.49	3	3
mol:GTP	-0.003	0.021	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.007	-10000	0	-10000	0	0
TSC2	0.014	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	0.015	0.031	-10000	0	-0.33	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.008	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.019	-10000	0	-10000	0	0
MAP3K5	0.011	0.001	-10000	0	-10000	0	0
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
apoptosis	0.011	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	3	3
EIF4B	0.034	0.018	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.012	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.003	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.022	0.035	-10000	0	-0.31	3	3
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	0.018	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	3	3
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.004	0.03	-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	3	-10000	0	3
RPS6	0.014	0	-10000	0	-10000	0	0
PPP5C	0.014	0	-10000	0	-10000	0	0
EIF4G1	0.014	0	-10000	0	-10000	0	0
IRS1	0.007	0.03	-10000	0	-0.38	3	3
INS	-0.003	0.052	-10000	0	-0.82	2	2
PTEN	0.013	0	-10000	0	-10000	0	0
PDK2	-0.003	0.027	-10000	0	-10000	0	0
EIF4EBP1	0.006	0.053	-10000	0	-0.38	9	9
PIK3CA	0.014	0	-10000	0	-10000	0	0
PPP2R5D	0.022	0.01	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.036	-10000	0	-0.5	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	0.036	-10000	0	-0.5	2	2
eIF4E/4E-BP1	0.014	0.047	-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	0.035	0	-9999	-10000	0	0
CDKN1B	0.04	0.006	-9999	-10000	0	0
CDKN1A	0.04	0.006	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.014	0	-9999	-10000	0	0
FOXO3	0.04	0.006	-9999	-10000	0	0
AKT1	0	0.005	-9999	-10000	0	0
BAD	0.014	0	-9999	-10000	0	0
AKT3	0.011	0.053	-9999	-0.36	10	10
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.039	0.02	-9999	-10000	0	0
AKT1/ASK1	0	0.004	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.014	0	-9999	-10000	0	0
RAF1	0.014	0	-9999	-10000	0	0
JNK cascade	0	0.004	-9999	-10000	0	0
TSC1	0.04	0.006	-9999	-10000	0	0
YWHAZ	0.014	0	-9999	-10000	0	0
AKT1/RAF1	0.039	0.006	-9999	-10000	0	0
EP300	0.011	0.037	-9999	-0.57	2	2
mol:GDP	0.033	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.04	0.006	-9999	-10000	0	0
YWHAQ	0.014	0	-9999	-10000	0	0
TBC1D4	0.026	0.014	-9999	-10000	0	0
MAP3K5	0.014	0	-9999	-10000	0	0
MAPKAP1	0.014	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.047	0.015	-9999	-10000	0	0
YWHAH	0.014	0	-9999	-10000	0	0
AKT1S1	0.04	0.006	-9999	-10000	0	0
CASP9	0.04	0.006	-9999	-10000	0	0
YWHAB	0.014	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.046	0.006	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.015	-9999	-10000	0	0
YWHAE	0.014	0	-9999	-10000	0	0
SRC	0.014	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0.01	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.002	-9999	-10000	0	0
CHUK	0.04	0.006	-9999	-10000	0	0
BAD/BCL-XL	0.053	0.006	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.018	0.016	-9999	-0.34	1	1
FOXO1-3a-4/14-3-3 family	0.062	0.02	-9999	-10000	0	0
PDPK1	0.013	0.026	-9999	-0.57	1	1
MDM2	0.04	0.006	-9999	-10000	0	0
MAPKKK cascade	-0.039	0.006	-9999	-10000	0	0
MDM2/Cbp/p300	0.051	0.019	-9999	-10000	0	0
TSC1/TSC2	0.047	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.014	-9999	-10000	0	0
glucose import	-0.12	0.16	-9999	-0.49	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.034	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.12	0.16	-9999	-0.49	1	1
GSK3A	0.04	0.006	-9999	-10000	0	0
FOXO1	0.04	0.006	-9999	-10000	0	0
GSK3B	0.04	0.006	-9999	-10000	0	0
SFN	0.006	0.074	-9999	-0.72	5	5
G1/S transition of mitotic cell cycle	0.047	0.006	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.05	0.022	-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	0.023	-9999	-9999
Ran/GTP	0.029	-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	0.04	-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	0.011	0.045	-9999	-0.69	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	0.053	-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	0.02	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	0.037	0.022	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.004	0.045	-9999	-0.54	3	3

pid_entity	TCGA.WA.A7H4	TCGA.WA.A7GZ	TCGA.UP.A6WW	TCGA.UF.A7JV
109_MAP3K5	0.059	0.059	0.059	0.059
47_PPARGC1A	0.014	0.014	0.014	-0.57
105_BMP4	0.014	0.014	0.014	0.014
105_BMP6	0.014	0.014	0.014	0.014
105_BMP7	0.014	0.014	0.014	0.014
105_BMP2	0.014	0.014	0.014	-0.82
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.018	0.013
84_STAT5B	0.039	0.039	-0.025	-0.023
84_STAT5A	0.039	0.039	-0.025	-0.023