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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	221
Syndecan-1-mediated signaling events	201
IL4-mediated signaling events	134
Syndecan-4-mediated signaling events	134
HIF-1-alpha transcription factor network	116
Osteopontin-mediated events	102
Glypican 2 network	82
IL23-mediated signaling events	74
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	0.4447	221	1771	8	-0.35	0.15	1000	-1000	-0.022	-1000
Syndecan-1-mediated signaling events	0.4044	201	6840	34	-0.72	0.014	1000	-1000	-0.069	-1000
IL4-mediated signaling events	0.2696	134	12249	91	-1.4	1.2	1000	-1000	-0.2	-1000
Syndecan-4-mediated signaling events	0.2696	134	9010	67	-0.69	0.092	1000	-1000	-0.1	-1000
HIF-1-alpha transcription factor network	0.2334	116	8816	76	-1	0.022	1000	-1000	-0.2	-1000
Osteopontin-mediated events	0.2052	102	3897	38	-0.44	0.014	1000	-1000	-0.12	-1000
Glypican 2 network	0.1650	82	328	4	-0.15	-0.14	1000	-1000	-0.043	-1000
IL23-mediated signaling events	0.1489	74	4445	60	-0.75	0.014	1000	-1000	-0.21	-1000
amb2 Integrin signaling	0.1449	72	5946	82	-0.6	0.014	1000	-1000	-0.11	-1000
TCGA08_p53	0.1348	67	472	7	-0.27	0.14	1000	-1000	-0.01	-1000
Syndecan-2-mediated signaling events	0.1308	65	4536	69	-0.44	0.024	1000	-1000	-0.07	-1000
Endothelins	0.1187	59	5678	96	-0.56	0.014	1000	-1000	-0.097	-1000
p75(NTR)-mediated signaling	0.0885	44	5508	125	-0.54	0.014	1000	-1000	-0.13	-1000
FOXA2 and FOXA3 transcription factor networks	0.0845	42	1972	46	-0.49	0.022	1000	-1000	-0.12	-1000
Visual signal transduction: Rods	0.0805	40	2116	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	-0.12	-1000
Effects of Botulinum toxin	0.0765	38	992	26	-0.21	0.014	1000	-1000	-0.075	-1000
Ephrin B reverse signaling	0.0744	37	1802	48	-0.16	0.15	1000	-1000	-0.093	-1000
Signaling events mediated by the Hedgehog family	0.0704	35	1823	52	-0.45	0.067	1000	-1000	-0.095	-1000
BMP receptor signaling	0.0704	35	2894	81	-0.36	0.048	1000	-1000	-0.11	-1000
Glypican 1 network	0.0704	35	1695	48	-0.36	0.033	1000	-1000	-0.062	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0704	35	2730	78	-0.16	0.043	1000	-1000	-0.093	-1000
Caspase cascade in apoptosis	0.0684	34	2569	74	-0.14	0.056	1000	-1000	-0.076	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0684	34	2364	68	-0.56	0.042	1000	-1000	-0.16	-1000
Coregulation of Androgen receptor activity	0.0664	33	2578	76	-0.5	0.041	1000	-1000	-0.055	-1000
IL12-mediated signaling events	0.0664	33	2941	87	-0.28	0.089	1000	-1000	-0.15	-1000
Signaling events regulated by Ret tyrosine kinase	0.0644	32	2680	82	-0.18	0.014	1000	-1000	-0.1	-1000
Glucocorticoid receptor regulatory network	0.0624	31	3614	114	-0.64	0.26	1000	-1000	-0.09	-1000
TCR signaling in naïve CD8+ T cells	0.0604	30	2854	93	-0.27	0.15	1000	-1000	-0.099	-1000
LPA4-mediated signaling events	0.0584	29	357	12	-0.11	0.021	1000	-1000	-0.033	-1000
Visual signal transduction: Cones	0.0584	29	1124	38	-0.18	0.014	1000	-1000	-0.089	-1000
Thromboxane A2 receptor signaling	0.0563	28	3015	105	-0.094	0.021	1000	-1000	-0.098	-1000
Canonical Wnt signaling pathway	0.0563	28	1436	51	-0.39	0.11	1000	-1000	-0.079	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0563	28	3420	120	-0.25	0.12	1000	-1000	-0.093	-1000
ErbB4 signaling events	0.0543	27	1925	69	-0.32	0.072	1000	-1000	-0.12	-1000
IL27-mediated signaling events	0.0523	26	1333	51	-0.18	0.062	1000	-1000	-0.11	-1000
BCR signaling pathway	0.0523	26	2627	99	-0.15	0.034	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0503	25	2190	85	-0.26	0.11	1000	-1000	-0.13	-1000
Nongenotropic Androgen signaling	0.0503	25	1335	52	-0.14	0.041	1000	-1000	-0.079	-1000
PDGFR-beta signaling pathway	0.0483	24	2361	97	-0.13	0.014	1000	-1000	-0.12	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0463	23	811	34	-0.065	0.014	1000	-1000	-0.078	-1000
Syndecan-3-mediated signaling events	0.0463	23	807	35	-0.21	0.014	1000	-1000	-0.078	-1000
Regulation of nuclear SMAD2/3 signaling	0.0443	22	3064	136	-0.37	0.36	1000	-1000	-0.087	-1000
IL1-mediated signaling events	0.0443	22	1379	62	-0.24	0.072	1000	-1000	-0.13	-1000
Signaling mediated by p38-gamma and p38-delta	0.0443	22	340	15	-0.13	0.024	1000	-1000	-0.051	-1000
Integrins in angiogenesis	0.0443	22	1898	84	-0.44	0.017	1000	-1000	-0.11	-1000
LPA receptor mediated events	0.0443	22	2260	102	-0.6	0.026	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	-0.079	-1000
Presenilin action in Notch and Wnt signaling	0.0423	21	1333	61	-0.39	0.04	1000	-1000	-0.08	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0423	21	1876	88	-0.36	0.067	1000	-1000	-0.13	-1000
Wnt signaling	0.0402	20	142	7	-0.074	0.011	1000	-1000	-0.045	-1000
Signaling events mediated by PTP1B	0.0362	18	1425	76	-0.16	0.03	1000	-1000	-0.11	-1000
Regulation of Androgen receptor activity	0.0362	18	1303	70	-0.52	0.033	1000	-1000	-0.077	-1000
IFN-gamma pathway	0.0342	17	1172	68	-0.19	0.036	1000	-1000	-0.12	-1000
Reelin signaling pathway	0.0342	17	952	56	-0.23	0.014	1000	-1000	-0.1	-1000
Signaling mediated by p38-alpha and p38-beta	0.0342	17	748	44	-0.18	0.014	1000	-1000	-0.064	-1000
Ephrin A reverse signaling	0.0322	16	118	7	-0.022	0.001	1000	-1000	-0.042	-1000
Arf6 signaling events	0.0322	16	1029	62	-0.16	0.041	1000	-1000	-0.078	-1000
EGFR-dependent Endothelin signaling events	0.0322	16	351	21	-0.098	0.014	1000	-1000	-0.087	-1000
ErbB2/ErbB3 signaling events	0.0302	15	1005	65	-0.32	0.026	1000	-1000	-0.082	-1000
PDGFR-alpha signaling pathway	0.0302	15	661	44	-0.13	0.033	1000	-1000	-0.062	-1000
Signaling events mediated by HDAC Class III	0.0302	15	620	40	-0.2	0.075	1000	-1000	-0.051	-1000
TRAIL signaling pathway	0.0302	15	733	48	-0.085	0.016	1000	-1000	-0.085	-1000
Regulation of Telomerase	0.0302	15	1592	102	-0.16	0.044	1000	-1000	-0.13	-1000
Plasma membrane estrogen receptor signaling	0.0302	15	1333	86	-0.3	0.03	1000	-1000	-0.1	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0282	14	770	54	-0.31	0.028	1000	-1000	-0.13	-1000
EPO signaling pathway	0.0282	14	815	55	-0.077	0.027	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	0.0282	14	1363	97	-0.19	0.035	1000	-1000	-0.12	-1000
S1P1 pathway	0.0282	14	504	36	-0.14	0.014	1000	-1000	-0.072	-1000
VEGFR1 specific signals	0.0282	14	815	56	-0.14	0.039	1000	-1000	-0.098	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0262	13	496	37	-0.083	0.014	1000	-1000	-0.069	-1000
Signaling events mediated by PRL	0.0262	13	452	34	-0.11	0.034	1000	-1000	-0.048	-1000
Noncanonical Wnt signaling pathway	0.0241	12	327	26	-0.08	0.014	1000	-1000	-0.11	-1000
Cellular roles of Anthrax toxin	0.0241	12	495	39	-0.043	0.019	1000	-1000	-0.035	-1000
Nectin adhesion pathway	0.0241	12	780	63	-0.14	0.04	1000	-1000	-0.085	-1000
FAS signaling pathway (CD95)	0.0241	12	601	47	-0.085	0.014	1000	-1000	-0.057	-1000
Retinoic acid receptors-mediated signaling	0.0241	12	734	58	-0.18	0.031	1000	-1000	-0.088	-1000
IL6-mediated signaling events	0.0221	11	886	75	-0.11	0.063	1000	-1000	-0.12	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0221	11	819	74	-0.31	0.082	1000	-1000	-0.11	-1000
JNK signaling in the CD4+ TCR pathway	0.0201	10	171	17	-0.039	0.036	1000	-1000	-0.079	-1000
IL2 signaling events mediated by PI3K	0.0201	10	589	58	-0.17	0.062	1000	-1000	-0.11	-1000
Rapid glucocorticoid signaling	0.0201	10	204	20	-0.061	0.014	1000	-1000	-0.058	-1000
FOXM1 transcription factor network	0.0201	10	522	51	-0.36	0.16	1000	-1000	-0.21	-1000
Ras signaling in the CD4+ TCR pathway	0.0201	10	182	17	-0.026	0.029	1000	-1000	-0.051	-1000
Aurora B signaling	0.0201	10	672	67	-0.32	0.031	1000	-1000	-0.083	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0181	9	504	52	-0.21	0.035	1000	-1000	-0.078	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0181	9	432	45	-0.085	0.035	1000	-1000	-0.11	-1000
S1P3 pathway	0.0181	9	392	42	-0.14	0.037	1000	-1000	-0.071	-1000
Circadian rhythm pathway	0.0161	8	192	22	-0.14	0.051	1000	-1000	-0.074	-1000
Ceramide signaling pathway	0.0161	8	661	76	-0.094	0.034	1000	-1000	-0.077	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0141	7	211	28	-0.075	0.022	1000	-1000	-0.07	-1000
a4b1 and a4b7 Integrin signaling	0.0141	7	39	5	-0.016	0.011	1000	-1000	-0.041	-1000
HIF-2-alpha transcription factor network	0.0141	7	327	43	-0.26	0.031	1000	-1000	-0.11	-1000
Paxillin-dependent events mediated by a4b1	0.0141	7	257	36	-0.067	0.025	1000	-1000	-0.084	-1000
IL2 signaling events mediated by STAT5	0.0141	7	156	22	-0.039	0.052	1000	-1000	-0.065	-1000
IGF1 pathway	0.0141	7	429	57	-0.089	0.021	1000	-1000	-0.12	-1000
Insulin Pathway	0.0141	7	518	74	-0.22	0.038	1000	-1000	-0.12	-1000
Class IB PI3K non-lipid kinase events	0.0141	7	21	3	-0.004	0.004	1000	-1000	-0.023	-1000
p38 MAPK signaling pathway	0.0141	7	339	44	-0.14	0.018	1000	-1000	-0.083	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0121	6	794	125	-0.12	0.094	1000	-1000	-0.11	-1000
S1P4 pathway	0.0121	6	154	25	-0.034	0.023	1000	-1000	-0.069	-1000
BARD1 signaling events	0.0101	5	333	57	-0.026	0.056	1000	-1000	-0.093	-1000
Hedgehog signaling events mediated by Gli proteins	0.0101	5	331	65	-0.095	0.063	1000	-1000	-0.084	-1000
Aurora A signaling	0.0101	5	348	60	-0.07	0.031	1000	-1000	-0.08	-1000
Arf6 downstream pathway	0.0101	5	222	43	-0.04	0.023	1000	-1000	-0.056	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0080	4	399	85	-0.07	0.058	1000	-1000	-0.096	-1000
Aurora C signaling	0.0080	4	29	7	-0.014	0.005	1000	-1000	-0.036	-1000
Regulation of p38-alpha and p38-beta	0.0080	4	259	54	-0.1	0.037	1000	-1000	-0.075	-1000
Class I PI3K signaling events	0.0080	4	314	73	-0.1	0.04	1000	-1000	-0.081	-1000
Arf6 trafficking events	0.0080	4	286	71	-0.25	0.047	1000	-1000	-0.089	-1000
PLK1 signaling events	0.0060	3	294	85	-0.019	0.036	1000	-1000	-0.061	-1000
ceramide signaling pathway	0.0060	3	194	49	-0.026	0.046	1000	-1000	-0.075	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0060	3	319	83	-0.082	0.066	1000	-1000	-0.084	-1000
TCGA08_rtk_signaling	0.0060	3	90	26	-0.031	0.048	1000	-1000	-0.026	-1000
E-cadherin signaling in keratinocytes	0.0060	3	141	43	-0.018	0.047	1000	-1000	-0.082	-1000
E-cadherin signaling events	0.0060	3	16	5	-0.005	0.013	1000	-1000	-0.058	-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	185	75	-0.035	0.032	1000	-1000	-0.08	-1000
S1P5 pathway	0.0040	2	45	17	-0.017	0.023	1000	-1000	-0.071	-1000
Alternative NF-kappaB pathway	0.0040	2	30	13	-0.008	0.014	1000	-1000	-0.085	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0020	1	37	23	-0.015	0.05	1000	-1000	-0.085	-1000
PLK2 and PLK4 events	0.0020	1	4	3	0.011	0.023	1000	-1000	-0.033	-1000
Insulin-mediated glucose transport	0.0020	1	37	32	-0.076	0.048	1000	-1000	-0.082	-1000
Signaling events mediated by HDAC Class I	0.0020	1	182	104	-0.13	0.061	1000	-1000	-0.093	-1000
FoxO family signaling	0.0020	1	108	64	-0.033	0.16	1000	-1000	-0.092	-1000
Atypical NF-kappaB pathway	0.0020	1	39	31	-0.006	0.048	1000	-1000	-0.068	-1000
E-cadherin signaling in the nascent adherens junction	0.0020	1	145	76	-0.016	0.06	1000	-1000	-0.1	-1000
mTOR signaling pathway	0.0000	0	41	53	-0.004	0.034	1000	-1000	-0.076	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	21	68	-0.12	0.062	1000	-1000	-0.074	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.067	-1000
Arf1 pathway	0.0000	0	9	54	-0.004	0.037	1000	-1000	-0.057	-1000
Total	NA	3123	177344	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	284	-10000	0	284
G1/S progression	0.13	0.14	0.24	284	-10000	0	284

×

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

×

IL4-mediated signaling events

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-1.1	0.5	-10000	0	-1.4	312	312
STAT6 (cleaved dimer)	-1.1	0.52	-10000	0	-1.4	343	343
IGHG1	-0.33	0.13	-10000	0	-0.47	108	108
IGHG3	-1	0.48	-10000	0	-1.3	331	331
AKT1	-0.4	0.18	-10000	0	-0.74	37	37
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.29	0.16	-10000	0	-0.72	26	26
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.41	0.18	-10000	0	-0.76	29	29
THY1	-1.1	0.55	-10000	0	-1.5	308	308
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	-0.76	100	100
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.41	0.18	-10000	0	-0.76	27	27
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	333	333
SOCS1	-0.64	0.28	-10000	0	-0.85	245	245
SOCS3	-0.42	0.2	-10000	0	-0.84	30	30
FCER2	-0.74	0.35	-10000	0	-1	207	207
PARP14	0.009	0.065	-10000	0	-0.82	3	3
CCL17	-1.1	0.51	-10000	0	-1.4	307	307
GRB2	0.014	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.33	0.15	-10000	0	-0.72	22	22
T cell proliferation	-1.1	0.53	-10000	0	-1.4	316	316
IL4R/JAK1	-1.1	0.5	-10000	0	-1.4	314	314
EGR2	-1.1	0.5	-10000	0	-1.4	312	312
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	185	185
CCL26	-1.1	0.51	-10000	0	-1.4	332	332
IL4R	-1.1	0.55	-10000	0	-1.5	318	318
PTPN6	0.035	0.007	-10000	0	-10000	0	0
IL13RA2	-1.1	0.52	-10000	0	-1.4	319	319
IL13RA1	-0.031	0.019	-10000	0	-10000	0	0
IRF4	-0.28	0.33	-10000	0	-0.94	84	84
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	45	45
mitosis	-0.38	0.18	-10000	0	-0.7	37	37
STAT6	-1.3	0.7	-10000	0	-1.7	328	328
SPI1	-0.017	0.075	-10000	0	-0.75	3	3
RPS6KB1	-0.36	0.17	-10000	0	-0.7	26	26
STAT6 (dimer)	-1.3	0.7	-10000	0	-1.7	328	328
STAT6 (dimer)/PARP14	-1.2	0.59	-10000	0	-1.5	327	327
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	-0.75	40	40
FRAP1	-0.4	0.18	-10000	0	-0.74	38	38
LTA	-1.1	0.51	-10000	0	-1.4	317	317
FES	0.014	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	1.2	0.62	1.6	328	-10000	0	328
CCL11	-1.2	0.49	-10000	0	-1.4	347	347
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.39	0.18	-10000	0	-0.75	38	38
IL2RG	-0.006	0.15	-10000	0	-0.79	17	17
IL10	-1.1	0.5	-10000	0	-1.4	308	308
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	305	305
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.77	0.31	-10000	0	-0.97	305	305
COL1A1	-0.67	0.38	-10000	0	-0.96	302	302
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	303	303
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	319	319
MYBL1	-0.003	0.12	-10000	0	-0.82	10	10
T-helper 2 cell differentiation	-0.79	0.33	-10000	0	-1	315	315
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	-0.74	27	27
mol:PI-3-4-5-P3	-0.4	0.18	-10000	0	-0.74	37	37
PI3K	-0.42	0.2	-10000	0	-0.79	39	39
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	-0.69	23	23
ITGB3	-1.1	0.51	-10000	0	-1.4	312	312
PIGR	-1.4	0.61	-10000	0	-1.7	376	376
IGHE	0.052	0.045	0.27	3	-10000	0	3
MAPKKK cascade	-0.3	0.14	-10000	0	-0.67	23	23
BCL6	0.014	0.002	-10000	0	-10000	0	0
OPRM1	-1.1	0.5	-10000	0	-1.4	311	311
RETNLB	-1.1	0.51	-10000	0	-1.4	312	312
SELP	-1.1	0.55	-10000	0	-1.5	318	318
AICDA	-1	0.48	-10000	0	-1.3	319	319

×

Syndecan-4-mediated signaling events

Figure S4. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S4. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.22	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	289	289
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	-0.63	225	225
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	222	222
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	222	222
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

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.69	0.48	-9999	-1.2	178	178
HDAC7	0.014	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.47	0.33	-9999	-0.85	119	119
SMAD4	0.014	0.026	-9999	-0.56	1	1
ID2	-0.69	0.48	-9999	-1.2	174	174
AP1	-0.045	0.14	-9999	-0.4	64	64
ABCG2	-0.7	0.48	-9999	-1.2	175	175
HIF1A	-0.083	0.061	-9999	-0.71	1	1
TFF3	-0.81	0.54	-9999	-1.3	228	228
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	173	173
NDRG1	-0.69	0.48	-9999	-1.2	173	173
SERPINE1	-0.91	0.55	-9999	-1.4	259	259
FECH	-0.69	0.48	-9999	-1.2	172	172
FURIN	-0.69	0.48	-9999	-1.2	173	173
NCOA2	-0.031	0.15	-9999	-0.57	38	38
EP300	-0.091	0.096	-9999	-0.44	4	4
HMOX1	-0.69	0.48	-9999	-1.2	174	174
BHLHE40	-0.69	0.48	-9999	-1.2	173	173
BHLHE41	-0.7	0.49	-9999	-1.2	175	175
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	-1.2	175	175
ABCB1	-0.2	0.32	-9999	-1.4	30	30
TFRC	-0.7	0.48	-9999	-1.2	178	178
CXCR4	-0.7	0.49	-9999	-1.2	177	177
TF	-0.86	0.54	-9999	-1.3	249	249
CITED2	-0.69	0.48	-9999	-1.2	173	173
HIF1A/ARNT	-0.79	0.61	-9999	-1.3	221	221
LDHA	-0.068	0.045	-9999	-10000	0	0
ETS1	-0.69	0.48	-9999	-1.2	173	173
PGK1	-0.69	0.48	-9999	-1.2	173	173
NOS2	-0.76	0.5	-9999	-1.2	197	197
ITGB2	-0.7	0.48	-9999	-1.2	176	176
ALDOA	-0.69	0.48	-9999	-1.2	173	173
Cbp/p300/CITED2	-0.67	0.49	-9999	-1.3	143	143
FOS	-0.06	0.19	-9999	-0.56	64	64
HK2	-0.69	0.48	-9999	-1.2	173	173
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	173	173
NPM1	-0.69	0.48	-9999	-1.2	175	175
EGLN1	-0.69	0.48	-9999	-1.2	162	162
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.69	0.48	-9999	-1.2	173	173
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	-1.2	176	176
VEGFA	-0.4	0.3	-9999	-0.94	29	29
HIF1A/JAB1	-0.043	0.036	-9999	-0.53	1	1
CP	-0.81	0.54	-9999	-1.3	233	233
CXCL12	-0.72	0.5	-9999	-1.2	178	178
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	173	173
EGLN3	-0.71	0.5	-9999	-1.2	182	182
CA9	-1	0.5	-9999	-1.3	316	316
TERT	-0.77	0.52	-9999	-1.3	203	203
ENO1	-0.69	0.48	-9999	-1.2	173	173
PFKL	-0.69	0.48	-9999	-1.2	173	173
NCOA1	0.013	0.002	-9999	-10000	0	0
ADM	-0.69	0.48	-9999	-1.2	173	173
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	-1.1	215	215
SLC2A1	-0.4	0.3	-9999	-0.95	33	33
LEP	-0.74	0.51	-9999	-1.3	189	189
HIF1A/ARNT/Cbp/p300	-0.49	0.34	-9999	-0.87	133	133
EPO	-0.4	0.32	-9999	-0.99	68	68
CREBBP	-0.09	0.092	-9999	-0.33	8	8
HIF1A/ARNT/Cbp/p300/HDAC7	-0.46	0.34	-9999	-0.9	87	87
PFKFB3	-0.69	0.48	-9999	-1.2	173	173
NT5E	-0.75	0.53	-9999	-1.3	186	186

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.27	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	-0.53	137	137
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	-0.57	156	156
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	173	173
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

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.023	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

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.58	0.44	-10000	0	-1.2	119	119
IL23A	-0.57	0.43	-10000	0	-1.2	102	102
NF kappa B1 p50/RelA/I kappa B alpha	-0.57	0.42	-10000	0	-1.1	131	131
positive regulation of T cell mediated cytotoxicity	-0.63	0.48	-10000	0	-1.2	138	138
ITGA3	-0.56	0.42	-10000	0	-1.2	105	105
IL17F	-0.38	0.27	-10000	0	-0.76	75	75
IL12B	-0.077	0.24	-10000	0	-0.86	43	43
STAT1 (dimer)	-0.62	0.48	-10000	0	-1.2	141	141
CD4	-0.55	0.4	-10000	0	-1.1	103	103
IL23	-0.58	0.43	-10000	0	-1.2	109	109
IL23R	-0.085	0.091	-10000	0	-0.7	6	6
IL1B	-0.6	0.45	-10000	0	-1.3	108	108
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.75	0.44	-10000	0	-1.2	195	195
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	138	138
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	109	109
ALOX12B	-0.66	0.48	-10000	0	-1.2	165	165
CXCL1	-0.59	0.45	-10000	0	-1.2	126	126
T cell proliferation	-0.63	0.48	-10000	0	-1.2	138	138
NFKBIA	0.008	0.037	-10000	0	-0.82	1	1
IL17A	-0.29	0.22	-10000	0	-0.63	23	23
PI3K	-0.58	0.42	-10000	0	-1.1	139	139
IFNG	-0.033	0.046	0.13	5	-0.12	48	53
STAT3 (dimer)	-0.55	0.4	-10000	0	-1.1	128	128
IL18R1	0.01	0.047	-10000	0	-0.7	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.34	0.25	-10000	0	-0.83	44	44
IL18/IL18R	-0.008	0.13	-10000	0	-0.58	14	14
macrophage activation	-0.029	0.015	-10000	0	-10000	0	0
TNF	-0.58	0.44	-10000	0	-1.2	107	107
STAT3/STAT4	-0.59	0.43	-10000	0	-1.1	143	143
STAT4 (dimer)	-0.61	0.47	-10000	0	-1.2	132	132
IL18	-0.01	0.11	-10000	0	-0.56	19	19
IL19	-0.69	0.52	-10000	0	-1.3	178	178
STAT5A (dimer)	-0.6	0.46	-10000	0	-1.2	128	128
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	211	211
MPO	-0.57	0.43	-10000	0	-1.2	117	117
positive regulation of humoral immune response	-0.63	0.48	-10000	0	-1.2	138	138
IL23/IL23R/JAK2/TYK2	-0.66	0.53	-10000	0	-1.3	136	136
IL6	-0.59	0.46	-10000	0	-1.3	117	117
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	112	112
keratinocyte proliferation	-0.63	0.48	-10000	0	-1.2	138	138
NOS2	-0.61	0.44	-10000	0	-1.2	140	140

×

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	-0.49	51	51
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	-0.57	47	47
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	-0.69	64	64
PTK2B	0.013	0.026	-10000	0	-0.57	1	1
mol:Ca2+	-0.055	0.21	-10000	0	-0.68	30	30
EDN1	-0.091	0.21	-10000	0	-0.46	21	21
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	17	17
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	-0.62	77	77
ADCY7	-0.19	0.25	-10000	0	-0.62	75	75
ADCY1	-0.21	0.27	-10000	0	-0.66	85	85
ADCY2	-0.29	0.26	-10000	0	-0.59	162	162
ADCY3	-0.19	0.25	-10000	0	-0.62	75	75
ADCY8	-0.2	0.26	-10000	0	-0.63	85	85
ADCY9	-0.19	0.25	-10000	0	-0.62	75	75
arachidonic acid secretion	-0.077	0.21	-10000	0	-0.52	55	55
ETB receptor/Endothelin-1/Gq/GTP	-0.053	0.14	-10000	0	-0.45	25	25
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	116	-0.62	91	207
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	-0.77	98	98
SLC9A1	-0.062	0.16	-10000	0	-0.33	48	48
mol:GDP	-0.06	0.18	-10000	0	-0.47	34	34
SLC9A3	-0.18	0.32	-10000	0	-0.71	102	102
RAF1	-0.079	0.19	-10000	0	-0.51	41	41
JUN	-0.038	0.18	-10000	0	-0.59	8	8
JAK2	-0.17	0.31	-10000	0	-0.67	70	70
mol:IP3	-0.071	0.17	-10000	0	-0.47	33	33
ETA receptor/Endothelin-1	-0.13	0.42	0.4	141	-0.71	85	226
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	-0.93	66	66
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	-0.45	33	33
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	-0.5	38	38
ETA receptor/Endothelin-1/Gq/GTP	-0.074	0.19	-10000	0	-0.46	42	42
MAPK14	-0.028	0.12	-10000	0	-0.7	4	4
TRPC6	-0.058	0.22	-10000	0	-0.72	30	30
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	-0.38	25	25
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	-0.52	15	15
cAMP biosynthetic process	-0.23	0.22	-10000	0	-0.57	106	106
MAPK8	-0.056	0.2	-10000	0	-0.59	26	26
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	-0.55	20	20
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	-0.47	33	33
MAP2K2	-0.088	0.23	-10000	0	-0.6	56	56
MAP2K1	-0.088	0.23	-10000	0	-0.6	56	56
EDNRA	-0.084	0.21	-10000	0	-0.4	49	49
positive regulation of muscle contraction	-0.14	0.27	-10000	0	-0.66	51	51
Gq family/GDP	-0.085	0.16	-10000	0	-0.55	20	20
HRAS/GTP	-0.075	0.17	-10000	0	-0.46	40	40
PRKCH	-0.061	0.16	-10000	0	-0.46	29	29
RAC1	0.014	0	-10000	0	-10000	0	0
PRKCA	-0.063	0.16	-10000	0	-0.46	29	29
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	-0.46	29	29
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	-0.47	36	36
PLA2G4A	-0.085	0.23	-10000	0	-0.57	55	55
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	-0.64	64	204
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	-0.54	5	5
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	-0.55	16	16
MAPK9	-0.047	0.18	-9999	-0.53	15	15
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	-0.86	1	1
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

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.23	0.39	-9999	-1.1	50	50
PCK1	-0.49	0.61	-9999	-1.3	171	171
HNF4A	-0.29	0.48	-9999	-1.3	62	62
KCNJ11	-0.33	0.51	-9999	-1.2	104	104
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	-1.2	143	143
NKX2-1	-0.088	0.34	-9999	-0.83	52	52
ACADM	-0.23	0.4	-9999	-1.1	51	51
TAT	-0.15	0.24	-9999	-0.85	19	19
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	-0.93	64	64
PKLR	-0.28	0.44	-9999	-1.1	73	73
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	-0.92	28	28
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	49	49
HMGCS1	-0.23	0.39	-9999	-1.1	50	50
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	49	49
ALDOB	-0.26	0.44	-9999	-1.2	57	57
AFP	-0.2	0.25	-9999	-0.64	74	74
BDH1	-0.23	0.39	-9999	-1.1	51	51
HADH	-0.24	0.41	-9999	-1.1	50	50
F2	-0.3	0.47	-9999	-1.3	48	48
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	-0.68	7	7
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	-0.83	59	59
FOXA2	-0.28	0.47	-9999	-1.2	61	61
ABCC8	-0.25	0.42	-9999	-1.1	54	54
ALB	-0.22	0.3	-9999	-0.79	77	77

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.014	0	-9999	-10000	0	0
GNAT1/GTP	-0.004	0.049	-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	-0.73	174	174
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	55	55
Na + (4 Units)	-0.29	0.24	-9999	-0.75	55	55
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	40	40
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 S16. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.016	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	129	129
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	-0.88	142	142
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	-0.46	18	18
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 S17. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.015	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	-0.4	24	24
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	-0.4	24	24

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.84	18	18
Ephrin B2/EPHB1-2	-0.13	0.22	-10000	0	-0.5	123	123
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.8	18	18
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	140	140
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	0.51	142	-10000	0	142
PIK3CA	0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.14	0.22	-10000	0	-0.84	18	18
angiogenesis	-0.021	0.1	-10000	0	-0.68	12	12
LCK	-0.021	0.13	-10000	0	-0.82	12	12

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.27	0.23	-10000	0	-0.86	14	14
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	-0.6	32	32
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	-0.58	45	45
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	-0.62	33	33
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	-0.58	45	45
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

×

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	-0.47	29	29
BMP7/USAG1	-0.16	0.24	-9999	-0.5	157	157
SMAD5/SKI	-0.039	0.14	-9999	-0.45	26	26
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	-0.46	25	25
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	-0.43	16	16
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 Stem cell factor receptor (c-Kit)

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
MAP4K1	-0.026	0.16	-10000	0	-0.42	17	17
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	-0.42	9	9
AKT1	-0.026	0.15	-10000	0	-0.4	62	62
BAD	-0.015	0.14	-10000	0	-0.37	56	56
megakaryocyte differentiation	-0.043	0.17	-10000	0	-0.43	74	74
GSK3B	-0.015	0.14	-10000	0	-0.4	13	13
RAF1	-0.003	0.14	-10000	0	-0.46	8	8
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	-0.43	62	62
HRAS/SPRED2	-0.054	0.11	-10000	0	-0.45	11	11
LYN/TEC/p62DOK	-0.071	0.15	-10000	0	-0.55	14	14
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	-0.43	93	93
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	-0.42	58	58
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	-10000	0	0
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	-0.44	5	5
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	56	56
SNAI2	-0.04	0.17	-10000	0	-0.44	69	69
positive regulation of cell proliferation	-0.068	0.27	-10000	0	-0.73	62	62
KITLG	0.011	0.047	-10000	0	-0.58	3	3
cell motility	-0.068	0.27	-10000	0	-0.73	62	62
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	62	62
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	-0.38	4	4
SHC/Grb2/SOS1	-0.057	0.13	-10000	0	-0.42	13	13
STAT5A	-0.052	0.23	-10000	0	-0.62	62	62
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

×

Caspase cascade in apoptosis

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
TOP1	-0.043	0.18	-10000	0	-0.42	84	84
ACTA1	-0.14	0.24	-10000	0	-0.61	90	90
NUMA1	-0.043	0.18	-10000	0	-0.42	84	84
SPTAN1	-0.069	0.24	-10000	0	-0.54	88	88
LIMK1	-0.069	0.24	-10000	0	-0.54	88	88
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	-0.71	91	91
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.014	0	-10000	0	-10000	0	0
PTK2	-0.043	0.18	-10000	0	-0.42	84	84
DIABLO	0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.067	0.23	-10000	0	-0.53	88	88
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	-0.54	88	88
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	-0.28	88	88
MAP3K1	-0.013	0.076	-10000	0	-0.22	31	31
TRADD	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.004	0.021	-10000	0	-0.4	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.069	0.24	-10000	0	-0.54	88	88
CASP9	0.014	0.001	-10000	0	-10000	0	0
DNA repair	0.008	0.064	-10000	0	-0.2	11	11
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	-0.53	83	83
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	-0.54	83	83
CASP7	0.006	0.064	0.31	16	-10000	0	16
KRT18	0.001	0.071	-10000	0	-0.44	10	10
apoptosis	-0.049	0.21	-10000	0	-0.67	35	35
DFFA	-0.069	0.24	-10000	0	-0.54	88	88
DFFB	-0.07	0.24	-10000	0	-0.55	88	88
PARP1	-0.008	0.064	0.2	11	-10000	0	11
actin filament polymerization	0.056	0.22	0.5	84	-10000	0	84
TNF	-0.025	0.17	-10000	0	-0.79	24	24
CYCS	-0.02	0.095	-10000	0	-0.27	36	36
SATB1	-0.009	0.12	-10000	0	-0.48	7	7
SLK	-0.069	0.24	-10000	0	-0.55	87	87
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	-0.38	2	2
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	-0.53	87	87
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	-0.36	3	3
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	-0.47	85	85
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	-0.55	87	87
APAF-1/Caspase 9	-0.001	0.078	0.45	10	-10000	0	10
nuclear fragmentation during apoptosis	-0.042	0.18	-10000	0	-0.41	84	84
CFL2	-0.058	0.22	-10000	0	-0.52	82	82
GAS2	-0.11	0.25	-10000	0	-0.58	90	90
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

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.12	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	84	84
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	-1.1	115	115
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	-0.5	21	21
TLE4	-0.01	0.17	-10000	0	-0.72	9	9
Jun/NFAT1-c-4/p21SNFT	-0.17	0.23	-10000	0	-0.92	19	19
AP-1/NFAT1-c-4	-0.38	0.44	-10000	0	-1.1	85	85
IKZF1	-0.02	0.2	-10000	0	-0.79	17	17
T-helper 2 cell differentiation	-0.075	0.23	-10000	0	-0.74	30	30
AP-1/NFAT1	-0.14	0.18	-10000	0	-0.62	35	35
CALM1	0.006	0.061	-10000	0	-10000	0	0
EGR2	-0.066	0.29	-10000	0	-1.4	15	15
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	-0.71	27	27
FOSL1	-0.011	0.14	-10000	0	-0.8	15	15
NFAT1-c-4/MAF/IRF4	-0.12	0.24	-10000	0	-0.94	18	18
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	-0.94	28	28
CTLA4	-0.18	0.43	-10000	0	-1	87	87
NFAT1-c-4 (dimer)/EGR1	-0.11	0.24	-10000	0	-0.96	20	20
NFAT1-c-4 (dimer)/EGR4	-0.16	0.28	-10000	0	-0.9	35	35
FOS	-0.097	0.19	-10000	0	-0.59	64	64
IFNG	-0.23	0.35	-10000	0	-0.89	69	69
T cell activation	-0.11	0.2	-10000	0	-0.74	9	9
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	-0.96	38	38
FASLG	-0.13	0.38	-10000	0	-1.3	37	37
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	-0.65	9	9
NFAT1-c-4/ICER1	-0.1	0.21	-10000	0	-0.9	17	17
GATA3	-0.016	0.15	-10000	0	-0.78	19	19
T-helper 1 cell differentiation	-0.21	0.35	-10000	0	-0.87	69	69
IL2RA	-0.31	0.38	-10000	0	-0.98	101	101
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.009	0.16	-10000	0	-0.61	14	14
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	-0.62	12	12
IRF4	-0.039	0.2	-10000	0	-0.75	34	34
PTGS2	-0.39	0.45	-10000	0	-1.1	96	96
CSF2	-0.56	0.51	-10000	0	-1.1	206	206
JunB/Fra1/NFAT1-c-4	-0.1	0.22	-10000	0	-0.95	15	15
IL4	-0.078	0.24	-10000	0	-0.79	27	27
IL5	-0.34	0.38	-10000	0	-0.99	65	65
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	-0.61	14	14
IL8	-0.42	0.46	-10000	0	-1.1	121	121
POU2F1	0.014	0.002	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.41	110	110
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	-0.41	146	146
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	-0.42	141	141
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	-0.4	121	121
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	-0.37	107	107
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	-0.37	110	110
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	-0.066	170	170
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	-0.41	138	138
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

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.09	0.23	-10000	0	-0.56	67	67
TBX21	-0.15	0.47	-10000	0	-1.2	62	62
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	-0.83	27	27
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	-0.8	57	57
HLA-DRB5	-0.007	0.12	-10000	0	-0.7	14	14
FASLG	-0.16	0.49	-10000	0	-1.2	71	71
NF kappa B2 p52/RelB	-0.22	0.37	-10000	0	-1	72	72
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	-0.6	93	93
CCL3	-0.14	0.45	-10000	0	-1.1	64	64
CCL4	-0.14	0.45	-10000	0	-1.1	62	62
HLA-A	0.002	0.087	-10000	0	-0.78	6	6
IL18/IL18R	0.024	0.14	-10000	0	-0.5	22	22
NOS2	-0.15	0.44	-10000	0	-1	72	72
IL12/IL12R/TYK2/JAK2/SPHK2	-0.067	0.21	-10000	0	-0.53	53	53
IL1R1	-0.13	0.42	-10000	0	-1.1	54	54
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	-0.83	67	67
RAB7A	-0.039	0.28	-10000	0	-0.73	20	20
lysosomal transport	-0.035	0.27	-10000	0	-0.69	20	20
FOS	-0.17	0.48	-10000	0	-1.2	75	75
STAT4 (dimer)	-0.087	0.37	-10000	0	-0.9	54	54
STAT5A (dimer)	-0.28	0.44	-10000	0	-1.1	95	95
GZMA	-0.16	0.5	-10000	0	-1.3	67	67
GZMB	-0.17	0.5	-10000	0	-1.1	83	83
HLX	0.009	0.064	-10000	0	-0.82	3	3
LCK	-0.15	0.48	-10000	0	-1.1	71	71
TCR/CD3/MHC II/CD4	-0.032	0.19	-10000	0	-0.58	35	35
IL2/IL2R	-0.069	0.2	-10000	0	-0.57	59	59
MAPK14	-0.064	0.32	-10000	0	-0.82	36	36
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	0.55	67	-10000	0	67
IL2RB	0.003	0.094	-10000	0	-0.78	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.074	0.34	-10000	0	-0.8	54	54
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	-1.2	76	76
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	-0.82	43	43
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	-0.87	79	79
T cell proliferation	-0.033	0.28	0.42	1	-0.65	36	37
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	-0.72	40	40
ATF2	-0.051	0.3	-10000	0	-0.78	32	32

×

Signaling events regulated by Ret tyrosine kinase

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	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	34	34
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

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.015	0.065	0.35	2	-10000	0	2
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	0.36	11	-0.56	1	12
PRL	-0.1	0.17	-10000	0	-0.66	13	13
cortisol/GR alpha (dimer)/TIF2	0.18	0.23	0.6	56	-10000	0	56
RELA	-0.003	0.091	-10000	0	-10000	0	0
FGG	0.11	0.27	0.58	21	-0.66	34	55
GR beta/TIF2	0.068	0.15	0.38	15	-0.38	7	22
IFNG	-0.37	0.34	-10000	0	-0.91	119	119
apoptosis	0.026	0.18	0.53	12	-0.63	5	17
CREB1	0.017	0.018	-10000	0	-10000	0	0
histone acetylation	0.001	0.12	0.41	5	-0.44	9	14
BGLAP	-0.052	0.14	-10000	0	-0.72	10	10
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	9	9
SMARCD1	0.015	0.007	-10000	0	-10000	0	0
MDM2	0.083	0.084	0.31	18	-10000	0	18
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	256	256
GSK3B	0.014	0.009	-10000	0	-10000	0	0
NR1I3	0.054	0.18	0.55	7	-0.77	3	10
CSN2	0.13	0.15	0.49	9	-0.54	2	11
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	-0.48	2	8
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.029	0.24	0.51	9	-0.85	24	33
JUN	-0.22	0.18	-10000	0	-0.63	40	40
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	77	77
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.1	0.095	0.38	6	-0.51	1	7
cortisol/GR alpha (monomer)	0.25	0.27	0.71	74	-10000	0	74
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	-0.79	113	113
AFP	-0.16	0.2	-10000	0	-0.82	31	31
SUV420H1	0.014	0	-10000	0	-10000	0	0
IRF1	0.12	0.16	0.52	11	-10000	0	11
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	-0.94	147	147
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	0.32	21	-10000	0	21
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	-0.8	114	114
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	-0.78	49	49
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	-0.72	7	7
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	-0.76	42	42
NFKB1	-0.003	0.091	-10000	0	-10000	0	0
MAPK8	-0.17	0.17	-10000	0	-0.58	39	39
MAPK9	0.014	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.018	0.19	0.53	12	-0.66	5	17
BAX	0.031	0.037	-10000	0	-10000	0	0
POMC	-0.17	0.32	-10000	0	-0.92	55	55
EP300	0.074	0.09	0.33	13	-0.44	2	15
cortisol/GR alpha (dimer)/p53	0.23	0.23	0.61	70	-0.52	1	71
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	-0.84	23	23
IL6	-0.18	0.34	-10000	0	-1	55	55
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.19	0.16	-10000	0	-0.79	11	11
IL2	-0.27	0.2	-10000	0	-0.69	49	49
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	-0.78	114	114
CDK5R1/CDK5	0.002	0.043	-10000	0	-0.63	2	2
NF kappa B1 p50/RelA/PKAc	0.015	0.12	-10000	0	-0.46	1	1
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	19	-0.49	1	20
JUN (dimer)	-0.22	0.18	-10000	0	-0.63	41	41
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	0.53	36	-10000	0	36
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	0.53	12	-0.63	5	17
cortisol/GR alpha (dimer)/Src-1	0.23	0.22	0.6	71	-10000	0	71
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	0.41	85	-10000	0	85
MMP1	-0.64	0.24	-10000	0	-0.72	435	435

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.068	0.16	-10000	0	-0.55	39	39
FYN	-0.038	0.23	-10000	0	-0.69	43	43
LAT/GRAP2/SLP76	-0.055	0.2	-10000	0	-0.59	44	44
IKBKB	0.014	0	-10000	0	-10000	0	0
AKT1	-0.013	0.16	-10000	0	-0.46	40	40
B2M	0.014	0.005	-10000	0	-10000	0	0
IKBKG	-0.019	0.043	-10000	0	-0.18	5	5
MAP3K8	0.01	0.045	-10000	0	-0.57	3	3
mol:Ca2+	-0.036	0.039	-10000	0	-0.12	22	22
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	-0.66	46	46
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	49	49
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	45	45
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	-0.29	30	30
GRAP2	-0.004	0.11	-10000	0	-0.66	13	13
mol:IP3	0.034	0.19	0.23	169	-0.47	30	199
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	-10000	0	-10000	0	0
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	-0.69	47	47
VAV1	-0.045	0.24	-10000	0	-0.71	45	45
Monovalent TCR/CD3	-0.021	0.17	-10000	0	-0.51	42	42
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	-0.76	50	50
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	-0.63	59	59
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	-0.57	41	41
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	-0.66	47	47
STIM1	0.076	0.078	-10000	0	-10000	0	0
RAS family/GTP	0.023	0.074	-10000	0	-0.18	18	18
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.048	0.26	-10000	0	-0.74	49	49
mol:DAG	-0.016	0.14	-10000	0	-0.4	37	37
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	-0.55	43	43
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.016	0.23	0.26	122	-0.61	35	157
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	-0.6	39	39
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	29	29
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	-0.39	39	39
IKK complex	0.032	0.054	-10000	0	-0.13	6	6
RAS family/GDP	-0.004	0.01	-10000	0	-0.086	3	3
MAP3K14	0.01	0.11	-10000	0	-0.31	18	18
PDPK1	-0.008	0.16	-10000	0	-0.45	37	37
TCR/CD3/MHC I/CD8/Fyn	-0.055	0.27	-10000	0	-0.8	47	47

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0.016	-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 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	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	8	8
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

×

Thromboxane A2 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
TGM2	-0.049	0.22	-10000	0	-0.82	36	36
GNB1/GNG2	-0.056	0.077	-10000	0	-0.22	29	29
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	-0.3	87	87
LYN	0.011	0.12	-10000	0	-0.51	12	12
RhoA/GTP	-0.033	0.049	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.032	0.18	-10000	0	-0.37	36	36
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	36	36
PRKCH	-0.037	0.18	-10000	0	-0.35	83	83
DNM1	-0.048	0.22	-10000	0	-0.82	37	37
TXA2/TP beta/beta Arrestin3	-0.025	0.069	-10000	0	-0.27	30	30
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	43	43
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	-0.37	91	91
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.073	0.25	-10000	0	-0.51	91	91
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.045	0.18	-10000	0	-0.55	24	24
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.009	0.13	-10000	0	-0.54	12	12
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	98	98
LCK	0.002	0.13	-10000	0	-0.51	12	12
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	-0.28	1	1
TGM2/GTP	-0.059	0.22	-10000	0	-0.48	43	43
MAPK11	-0.009	0.13	-10000	0	-0.25	8	8
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	98	98
RAB11/GDP	0.014	0.002	-10000	0	-10000	0	0
ICAM1	-0.029	0.16	-10000	0	-0.34	48	48
cAMP biosynthetic process	-0.045	0.18	-10000	0	-0.38	48	48
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	-0.36	15	15
VCAM1	-0.038	0.18	-10000	0	-0.33	105	105
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	33	33
PGI2/IP	-0.024	0.12	-10000	0	-0.64	19	19
PRKACA	0.004	0.085	-10000	0	-0.36	22	22
Gq family/GDP/G beta5/gamma2	0.009	0.076	-10000	0	-0.49	3	3
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	-0.51	53	53
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	-0.6	11	11
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	-0.79	20	20
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	42	42
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	97	97
muscle contraction	-0.062	0.24	-10000	0	-0.48	98	98
PRKCZ	-0.032	0.18	-10000	0	-0.36	47	47
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	-0.36	86	86
MAPKKK cascade	-0.058	0.22	-10000	0	-0.44	92	92
SELE	-0.043	0.18	-10000	0	-0.38	86	86
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

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.4	4	4
WIF1	-0.26	0.3	-10000	0	-0.58	219	219
beta catenin/RanBP3	-0.013	0.088	0.41	6	-10000	0	6
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	-0.38	2	2
FZD1	0.005	0.087	-10000	0	-0.78	6	6
AXIN2	-0.012	0.21	-10000	0	-1.4	10	10
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	-10000	0	0
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 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
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	0.46	27	-10000	0	27
SHC 2-3/Grb2	-0.12	0.14	-10000	0	-0.52	25	25
SHC1	0.014	0	-10000	0	-10000	0	0
SHC2	-0.11	0.14	0.21	1	-0.43	49	50
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	-0.4	14	14
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	5	5
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	0.25	2	-0.57	100	102
SOS1	0.014	0	-10000	0	-10000	0	0
MCF2L	-0.19	0.26	-10000	0	-0.68	70	70
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	5	5
NGF (dimer)/TRKA/GRIT	-0.14	0.25	-10000	0	-0.56	129	129
neuron projection morphogenesis	-0.042	0.13	-10000	0	-0.5	3	3
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	-10000	0	0
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	-0.5	16	16
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 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
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	77	77
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	-0.48	27	27
STAT1 (dimer)	-0.043	0.15	-10000	0	-0.57	27	27
MAPK1	-0.041	0.17	-10000	0	-0.48	27	27
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	-0.4	2	2
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

×

IL27-mediated signaling events

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
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	0.62	30	-10000	0	30
IL27/IL27R/JAK1	-0.11	0.21	-10000	0	-0.82	23	23
TBX21	-0.1	0.26	-10000	0	-0.69	50	50
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	0.62	30	-10000	0	30
T cell proliferation during immune response	0.062	0.19	0.62	30	-10000	0	30
MAPKKK cascade	-0.062	0.19	-10000	0	-0.62	30	30
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	106	106
IL27/IL27R/JAK2/TYK2	-0.063	0.19	-10000	0	-0.63	30	30
positive regulation of T cell mediated cytotoxicity	-0.062	0.19	-10000	0	-0.62	30	30
STAT1 (dimer)	-0.18	0.31	0.52	1	-0.92	47	48
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	-0.62	38	38
IL12/IL12R/TYK2/JAK2	-0.064	0.19	-10000	0	-0.68	20	20
IL17A	-0.019	0.12	-10000	0	-0.64	8	8
mast cell activation	0.062	0.19	0.62	30	-10000	0	30
IFNG	-0.019	0.051	-10000	0	-0.11	109	109
T cell differentiation	-0.007	0.009	-10000	0	-0.024	71	71
STAT3 (dimer)	-0.052	0.18	-10000	0	-0.64	24	24
STAT5A (dimer)	-0.052	0.18	-10000	0	-0.64	24	24
STAT4 (dimer)	-0.063	0.2	-10000	0	-0.63	34	34
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	-0.69	19	19
IL18	-0.005	0.082	-10000	0	-0.42	19	19
positive regulation of mast cell cytokine production	-0.051	0.18	-10000	0	-0.62	25	25
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

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.03	0.15	-10000	0	-0.44	25	25
IKBKB	-0.008	0.079	-10000	0	-0.28	2	2
AKT1	-0.029	0.12	-10000	0	-0.29	41	41
IKBKG	-0.007	0.082	-10000	0	-0.29	7	7
CALM1	-0.045	0.12	-10000	0	-0.41	29	29
PIK3CA	0.014	0	-10000	0	-10000	0	0
MAP3K1	-0.059	0.21	-10000	0	-0.63	31	31
MAP3K7	0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.12	-10000	0	-0.44	29	29
DOK1	0.012	0.037	-10000	0	-0.82	1	1
AP-1	-0.021	0.097	-10000	0	-0.27	10	10
LYN	0.012	0.037	-10000	0	-0.82	1	1
BLNK	-0.042	0.17	-10000	0	-0.57	48	48
SHC1	0.014	0	-10000	0	-10000	0	0
BCR complex	-0.14	0.28	-10000	0	-0.63	109	109
CD22	-0.13	0.27	-10000	0	-0.81	55	55
CAMK2G	-0.034	0.11	-10000	0	-0.43	8	8
CSNK2A1	0.014	0	-10000	0	-10000	0	0
INPP5D	0.01	0.045	-10000	0	-0.57	3	3
SHC/GRB2/SOS1	-0.11	0.19	-10000	0	-0.63	30	30
GO:0007205	-0.056	0.13	-10000	0	-0.45	29	29
SYK	0.01	0.045	-10000	0	-0.57	3	3
ELK1	-0.046	0.12	-10000	0	-0.42	30	30
NFATC1	-0.068	0.19	-10000	0	-0.48	71	71
B-cell antigen/BCR complex	-0.14	0.28	-10000	0	-0.63	109	109
PAG1/CSK	-0.003	0.04	-10000	0	-0.63	2	2
NFKBIB	0.008	0.03	-10000	0	-10000	0	0
HRAS	-0.049	0.13	-10000	0	-0.44	29	29
NFKBIA	0.008	0.03	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.014	0.025	-10000	0	-10000	0	0
RasGAP/Csk	-0.11	0.22	-10000	0	-0.55	79	79
mol:GDP	-0.054	0.12	-10000	0	-0.42	29	29
PTEN	0.014	0	-10000	0	-10000	0	0
CD79B	-0.02	0.15	-10000	0	-0.71	23	23
NF-kappa-B/RelA/I kappa B alpha	0.015	0.024	-10000	0	-10000	0	0
GRB2	0.014	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.094	0.23	-10000	0	-0.55	82	82
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
mol:IP3	-0.057	0.13	-10000	0	-0.45	29	29
CSK	0.014	0	-10000	0	-10000	0	0
FOS	-0.071	0.15	-10000	0	-0.43	49	49
CHUK	-0.007	0.082	-10000	0	-0.29	7	7
IBTK	0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.07	0.13	-10000	0	-0.57	15	15
PTPN6	-0.12	0.25	-10000	0	-0.75	55	55
RELA	0.014	0	-10000	0	-10000	0	0
BCL2A1	0.007	0.04	-10000	0	-0.13	32	32
VAV2	-0.15	0.27	-10000	0	-0.74	75	75
ubiquitin-dependent protein catabolic process	0.013	0.029	-10000	0	-10000	0	0
BTK	-0.003	0.035	0.35	3	-10000	0	3
CD19	-0.15	0.3	-10000	0	-0.77	83	83
MAP4K1	-0.008	0.13	-10000	0	-0.76	14	14
CD72	-0.095	0.28	-10000	0	-0.82	65	65
PAG1	0.01	0.053	-10000	0	-0.82	2	2
MAPK14	-0.04	0.18	-10000	0	-0.54	27	27
SH3BP5	0.01	0.045	-10000	0	-0.57	3	3
PIK3AP1	-0.061	0.16	-10000	0	-0.47	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.09	0.2	-10000	0	-0.58	45	45
RAF1	-0.038	0.13	-10000	0	-0.41	29	29
RasGAP/p62DOK/SHIP	-0.1	0.21	-10000	0	-0.77	23	23
CD79A	-0.14	0.31	-10000	0	-0.74	104	104
re-entry into mitotic cell cycle	-0.022	0.097	-10000	0	-0.27	10	10
RASA1	0.011	0.037	-10000	0	-0.57	2	2
MAPK3	-0.017	0.11	-10000	0	-0.42	3	3
MAPK1	-0.017	0.11	-10000	0	-0.42	3	3
CD72/SHP1	-0.12	0.31	-10000	0	-0.84	57	57
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	-0.043	0.18	-10000	0	-0.53	29	29
actin cytoskeleton organization	-0.092	0.24	-10000	0	-0.61	74	74
NF-kappa-B/RelA	0.034	0.047	-10000	0	-10000	0	0
Calcineurin	-0.047	0.088	-10000	0	-0.44	3	3
PI3K	-0.13	0.22	-10000	0	-0.62	71	71
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.069	0.13	-10000	0	-0.47	33	33
SOS1	0.014	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.063	0.23	-10000	0	-0.76	36	36
DAPP1	-0.092	0.21	-10000	0	-0.75	34	34
cytokine secretion	-0.062	0.18	-10000	0	-0.44	71	71
mol:DAG	-0.057	0.13	-10000	0	-0.45	29	29
PLCG2	0.013	0.026	-10000	0	-0.57	1	1
MAP2K1	-0.028	0.12	-10000	0	-0.39	15	15
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.25	-10000	0	-0.64	79	79
mol:PI-3-4-5-P3	-0.09	0.15	-10000	0	-0.41	69	69
ETS1	-0.027	0.11	-10000	0	-0.42	6	6
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.23	-10000	0	-0.55	89	89
B-cell antigen/BCR complex/LYN	-0.094	0.2	-10000	0	-0.73	28	28
MALT1	0.014	0	-10000	0	-10000	0	0
TRAF6	0.014	0	-10000	0	-10000	0	0
RAC1	-0.1	0.26	-10000	0	-0.66	74	74
B-cell antigen/BCR complex/LYN/SYK	-0.13	0.27	-10000	0	-0.88	45	45
CARD11	-0.073	0.17	-10000	0	-0.5	53	53
FCGR2B	0.006	0.068	-10000	0	-0.57	7	7
PPP3CA	0.014	0	-10000	0	-10000	0	0
BCL10	0.014	0	-10000	0	-10000	0	0
IKK complex	0.007	0.039	-10000	0	-10000	0	0
PTPRC	-0.004	0.11	-10000	0	-0.68	13	13
PDPK1	-0.029	0.12	-10000	0	-0.29	41	41
PPP3CB	0.014	0	-10000	0	-10000	0	0
PPP3CC	0.014	0	-10000	0	-10000	0	0
POU2F2	0.008	0.04	-10000	0	-0.14	30	30

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.13	0.24	-10000	0	-0.55	121	121
cell-cell adhesion	0.11	0.17	0.72	5	-10000	0	5
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	-0.72	5	5
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	-0.42	1	1
MAPK1	0.027	0.083	-10000	0	-0.4	3	3
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	-0.82	22	22
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	-0.8	5	5
Ephrin B/EPHB1/Src/Paxillin	0.005	0.098	-10000	0	-0.51	3	3

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.27	19	19
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	19	19
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

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.42	12	12
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	-0.44	1	1
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	-0.61	22	22
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	-0.46	1	1
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	-0.4	89	89
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	-0.47	1	1
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

×

Nephrin/Neph1 signaling in the kidney podocyte

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
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	-0.79	10	10
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	-0.55	34	34
Nephrin/NEPH1/beta Arrestin2	-0.026	0.16	-10000	0	-0.81	10	10
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	-0.52	36	36
Nephrin/NEPH1/ZO-1	-0.052	0.16	-10000	0	-0.56	36	36

×

Syndecan-3-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	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	-0.43	11	11
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	-0.67	12	12
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	-0.44	11	11
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 S43. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.56	16	16
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	0.6	51	-10000	0	51
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	-0.52	5	5
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	-0.68	17	17
SMAD3/SMAD4/MEF2C	-0.14	0.26	-10000	0	-0.68	45	45
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	102	102
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	-0.66	14	14
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	-0.59	12	12
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	202	202
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	-0.49	14	14
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	-0.47	18	18
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	-0.37	3	3
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

×

IL1-mediated signaling events

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	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	-0.71	2	2
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	-0.85	1	1
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

×

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	-0.38	14	14
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	-0.58	10	10
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	-0.57	29	29
GPR124	0.009	0.064	-9999	-0.82	3	3
MAPK1	-0.11	0.15	-9999	-0.57	29	29
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	-0.47	20	20
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	-0.48	6	6
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	-0.48	6	6
cell migration	0.016	0.12	-9999	-0.44	4	4
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	-0.63	19	19
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

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.34	22	22
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	-0.39	4	4
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	-0.38	12	12
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	-0.46	17	17
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	-0.44	3	3
GNAQ	0.005	0.059	-9999	-0.3	12	12
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	-0.34	22	22
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	-0.4	4	4
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	-0.41	16	16
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	-0.3	88	88
GNA15	0.004	0.066	-9999	-0.32	13	13
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	-0.3	16	16
Rac1/GTP	-0.009	0.11	-9999	-0.94	7	7
MMP2	-0.09	0.28	-9999	-0.76	70	70

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.14	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 S49. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.37	16	16
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	-0.36	16	16
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 S50. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.054	0.23	-10000	0	-0.89	21	21
NCK1/PAK1/Dok-R	-0.028	0.09	-10000	0	-0.41	21	21
NCK1/Dok-R	-0.052	0.22	-10000	0	-1.1	21	21
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.005	0.041	0.24	12	-10000	0	12
RELA	0.014	0	-10000	0	-10000	0	0
SHC1	0.014	0.002	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.079	0.25	-10000	0	-0.84	47	47
TNIP2	0.014	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.046	0.2	-10000	0	-0.99	21	21
FN1	-0.36	0.41	-10000	0	-0.82	221	221
PLD2	0.031	0.25	-10000	0	-1.1	21	21
PTPN11	0.014	0	-10000	0	-10000	0	0
GRB14	-0.045	0.18	-10000	0	-0.6	47	47
ELK1	0.045	0.23	-10000	0	-0.99	21	21
GRB7	0.005	0.083	-10000	0	-0.74	6	6
PAK1	0.012	0.037	-10000	0	-0.82	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.34	0.36	-10000	0	-0.86	131	131
CDKN1A	0.061	0.19	-10000	0	-0.65	11	11
ITGA5	-0.25	0.39	-10000	0	-0.82	155	155
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.054	0.22	-10000	0	-1.1	21	21
CRK	0.014	0	-10000	0	-10000	0	0
mol:NO	0.058	0.18	-10000	0	-0.64	21	21
PLG	0.02	0.25	-10000	0	-1.1	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.034	0.21	-10000	0	-0.85	21	21
GRB2	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.011	0.045	-10000	0	-0.57	3	3
ANGPT2	0.018	0.19	-10000	0	-0.61	25	25
BMX	-0.006	0.28	-10000	0	-1.2	21	21
ANGPT1	0.015	0.23	-10000	0	-1.2	14	14
tube development	0.054	0.21	-10000	0	-0.73	13	13
ANGPT4	0.008	0.008	-10000	0	-10000	0	0
response to hypoxia	0.001	0.015	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.004	0.27	-10000	0	-1.2	21	21
alpha5/beta1 Integrin	-0.2	0.29	-10000	0	-0.63	156	156
FGF2	-0.008	0.12	-10000	0	-0.63	16	16
STAT5A (dimer)	0.056	0.23	-10000	0	-0.85	11	11
mol:L-citrulline	0.058	0.18	-10000	0	-0.64	21	21
AGTR1	-0.042	0.17	-10000	0	-0.58	46	46
MAPK14	0.034	0.26	-10000	0	-1.1	21	21
Tie2/SHP2	-0.032	0.18	-10000	0	-1.2	11	11
TEK	0.011	0.21	-10000	0	-1.3	11	11
RPS6KB1	0.057	0.22	-10000	0	-0.85	21	21
Angiotensin II/AT1	-0.029	0.13	-10000	0	-0.43	46	46
Tie2/Ang1/GRB2	0.027	0.26	-10000	0	-1.2	21	21
MAPK3	0.04	0.23	-10000	0	-1	21	21
MAPK1	0.04	0.23	-10000	0	-1	21	21
Tie2/Ang1/GRB7	0.022	0.27	-10000	0	-1.2	21	21
NFKB1	0.014	0	-10000	0	-10000	0	0
MAPK8	0.027	0.26	-10000	0	-1.1	21	21
PI3K	0.045	0.25	-10000	0	-1	21	21
FES	0.034	0.26	-10000	0	-1.1	21	21
Crk/Dok-R	-0.052	0.22	-10000	0	-1.1	21	21
Tie2/Ang1/ABIN2	0.027	0.26	-10000	0	-1.2	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.057	0.21	-10000	0	-0.79	21	21
STAT5A	0.014	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.057	0.22	-10000	0	-0.85	21	21
Tie2/Ang2	0.039	0.26	-10000	0	-1	12	12
Tie2/Ang1	0.023	0.28	-10000	0	-1.2	21	21
FOXO1	0.058	0.22	-10000	0	-0.79	21	21
ELF1	0.017	0.056	-10000	0	-0.58	4	4
ELF2	0.028	0.25	-10000	0	-1.1	21	21
mol:Choline	0.033	0.24	-10000	0	-1.1	21	21
cell migration	-0.09	0.087	-10000	0	-10000	0	0
FYN	0.05	0.23	-10000	0	-0.84	13	13
DOK2	0.008	0.069	-10000	0	-0.76	4	4
negative regulation of cell cycle	0.063	0.18	-10000	0	-0.59	11	11
ETS1	0.013	0.074	-10000	0	-0.8	3	3
PXN	0.067	0.19	-10000	0	-0.7	21	21
ITGB1	0.012	0.037	-10000	0	-0.82	1	1
NOS3	0.056	0.2	-10000	0	-0.74	21	21
RAC1	0.014	0	-10000	0	-10000	0	0
TNF	-0.019	0.18	-10000	0	-0.78	24	24
MAPKKK cascade	0.033	0.24	-10000	0	-1.1	21	21
RASA1	0.011	0.037	-10000	0	-0.57	2	2
Tie2/Ang1/Shc	0.028	0.26	-10000	0	-1.2	21	21
NCK1	0.014	0	-10000	0	-10000	0	0
vasculogenesis	0.06	0.17	-10000	0	-0.58	21	21
mol:Phosphatidic acid	0.033	0.24	-10000	0	-1.1	21	21
mol:Angiotensin II	0	0.007	-10000	0	-10000	0	0
mol:NADP	0.058	0.18	-10000	0	-0.64	21	21
Rac1/GTP	-0.048	0.17	-10000	0	-0.79	21	21
MMP2	-0.037	0.3	-10000	0	-1.1	21	21

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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

×

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	-0.4	10	10
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	0.23	2	-0.35	8	10
EGFR	-0.02	0.15	-10000	0	-0.76	20	20
EGF/EGFR	-0.1	0.15	-10000	0	-0.44	48	48
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	0.23	1	-0.54	62	63
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	-0.37	7	8
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	0.22	2	-0.37	15	17
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	-0.23	2	10
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	0.23	1	-0.35	6	7
Crk/p130 Cas	-0.013	0.083	-10000	0	-0.36	2	2
DOK1	-0.05	0.14	0.25	1	-0.41	15	16
JAK2	-0.063	0.12	-10000	0	-0.37	26	26
Jak2/Leptin Receptor/Leptin	-0.074	0.12	-10000	0	-0.47	4	4
PIK3R1	0.01	0.045	-10000	0	-0.57	3	3
PTPN1	-0.03	0.093	0.23	2	-0.35	8	10
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	-0.5	1	1
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.066	0.1	-10000	0	-0.43	2	2
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	-0.54	2	2
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	-0.54	2	2
CSF1/CSF1R	-0.018	0.093	-10000	0	-0.42	4	4
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	11	12
STAT5A	-0.039	0.088	0.21	1	-0.32	11	12
GRB2	0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.11	0.23	0.23	1	-0.57	92	93
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	-0.33	21	21
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

×

Regulation of Androgen receptor activity

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
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	-0.57	26	26
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	-0.53	14	14
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	-0.51	8	8
AR/RACK1/Src	-0.035	0.12	-9999	-0.48	14	14
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	-0.58	17	17
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	78	78
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	-0.48	18	18
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	-0.63	2	2
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

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.053	0.19	-9999	-0.41	91	91
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	-0.73	19	19
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	-0.83	19	19
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	80	80
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	92	92
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	-0.7	38	38
STAT1	-0.066	0.23	-9999	-0.83	19	19
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	91	91
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	-0.41	91	91
CREBBP	0.014	0.001	-9999	-10000	0	0
RAPGEF1	0.014	0	-9999	-10000	0	0

×

Reelin signaling pathway

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
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	-0.68	33	33
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	-0.66	10	10
ARHGEF2	0.014	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.13	0.29	-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	-0.56	35	35
RELN/LRP8	-0.08	0.16	-9999	-0.63	11	11
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.088	0.16	-9999	-0.59	18	18
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	-0.61	10	10
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

×

Signaling mediated by p38-alpha and p38-beta

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
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	-0.4	13	13
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	-0.36	13	13
NOS2	-0.12	0.31	-9999	-0.75	86	86
DDIT3	-0.049	0.16	-9999	-0.52	18	18
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	-0.54	18	18
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	-0.46	19	19
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

×

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

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.005	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	15	15
ARAP2	0.007	0.063	-9999	-0.57	6	6
mol:GDP	-0.011	0.077	-9999	-0.29	15	15
mol:PI-3-4-5-P3	0	0	-9999	-0.001	9	9
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	-0.31	15	15
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	16	16
actin filament binding	0	0	-9999	-0.001	15	15
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	11	11
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	12	12
endosomal lumen acidification	0	0	-9999	-0.001	14	14
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	2	2
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	11	11
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	-0.45	19	19
alphaIIb/beta3 Integrin	-0.08	0.21	-9999	-0.63	63	63

×

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	82	82
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	-0.53	35	35
MAPK1	-0.1	0.23	-9999	-0.53	35	35
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	-0.32	16	16
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	-0.32	16	16
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	-0.47	34	34
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

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0	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	-0.44	3	3
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	-0.42	10	10
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

×

Signaling events mediated by HDAC Class III

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
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 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
TNFSF10	-0.001	0.11	-10000	0	-0.79	9	9
positive regulation of NF-kappaB transcription factor activity	-0.029	0.13	-10000	0	-0.6	24	24
MAP2K4	0.009	0.1	-10000	0	-0.48	1	1
IKBKB	0.014	0	-10000	0	-10000	0	0
TNFRSF10B	0.014	0	-10000	0	-10000	0	0
TNFRSF10A	0.011	0.037	-10000	0	-0.57	2	2
SMPD1	0.016	0.036	-10000	0	-0.26	8	8
IKBKG	0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.01	0.14	-10000	0	-0.78	15	15
TRAIL/TRAILR2	-0.011	0.081	-10000	0	-0.6	9	9
TRAIL/TRAILR3	-0.029	0.13	-10000	0	-0.6	24	24
TRAIL/TRAILR1	-0.013	0.085	-10000	0	-0.57	11	11
TRAIL/TRAILR4	-0.029	0.13	-10000	0	-0.6	24	24
TRAIL/TRAILR1/DAP3/GTP	-0.01	0.067	-10000	0	-0.5	8	8
IKK complex	-0.025	0.062	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.013	0.084	-10000	0	-0.6	9	9
MAP3K1	0.001	0.11	-10000	0	-0.51	1	1
TRAILR4 (trimer)	-0.01	0.14	-10000	0	-0.78	15	15
TRADD	0.014	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.011	0.037	-10000	0	-0.56	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.006	0.11	-10000	0	-0.54	1	1
CFLAR	0.014	0	-10000	0	-10000	0	0
MAPK1	0.013	0.084	-10000	0	-0.6	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.064	0.16	-10000	0	-0.46	67	67
mol:ceramide	0.016	0.036	-10000	0	-0.26	8	8
FADD	-0.085	0.27	-10000	0	-0.82	59	59
MAPK8	0.013	0.11	-10000	0	-0.48	4	4
TRAF2	0.002	0.098	-10000	0	-0.82	7	7
TRAILR3 (trimer)	-0.01	0.14	-10000	0	-0.78	15	15
CHUK	0.014	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.075	0.19	-10000	0	-0.54	67	67
DAP3	0.014	0	-10000	0	-10000	0	0
CASP10	-0.053	0.16	0.28	12	-0.44	64	76
JNK cascade	-0.029	0.13	-10000	0	-0.6	24	24
TRAIL (trimer)	-0.001	0.11	-10000	0	-0.79	9	9
TNFRSF10C	-0.01	0.14	-10000	0	-0.78	15	15
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.065	0.16	-10000	0	-0.47	67	67
TRAIL/TRAILR2/FADD	-0.074	0.19	-10000	0	-0.54	67	67
cell death	0.016	0.036	-10000	0	-0.26	8	8
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.005	0.11	-10000	0	-0.54	1	1
TRAILR2 (trimer)	0.014	0	-10000	0	-10000	0	0
CASP8	-0.001	0.022	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.063	0.16	-10000	0	-0.46	67	67

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.14	0.3	-9999	-0.71	84	84
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	9	9
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	-0.67	82	82
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	-0.64	53	53
Mad/Max	0.013	0.044	-9999	-0.41	5	5
TERT	-0.15	0.31	-9999	-0.73	84	84
CCND1	-0.13	0.29	-9999	-0.77	35	35
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	-10000	0	0
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	-0.69	45	45
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	-0.7	54	54
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	-0.66	38	38
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	-0.64	48	48
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	-0.64	53	53
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	-0.64	49	49
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

×

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	-0.48	4	4
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	40	40
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	-0.7	1	1
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	-0.38	15	15
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	-0.64	37	37
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	-0.64	7	7
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	-0.6	1	1
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

×

EPO 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	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	-0.73	5	5
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	-0.47	1	2
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	-0.54	4	4
BCL2	0.017	0.16	-10000	0	-0.69	10	10

×

Fc-epsilon receptor I signaling in mast cells

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
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	-0.52	13	13
mol:PIP3	-0.069	0.19	-9999	-0.55	27	27
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	27	27
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	-0.42	3	3
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	-0.55	31	31
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	-0.66	26	26
Antigen/IgE/Fc epsilon R1	-0.14	0.19	-9999	-0.61	26	26
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	-0.48	23	23
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	-0.49	13	13
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	-0.57	31	31
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	-0.49	16	16
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.071	0.11	-9999	-0.52	8	8
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	-0.51	16	16
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.16	-9999	-0.56	24	24
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.06	0.18	-9999	-0.52	21	21
MAP2K2	0.03	0.02	-9999	-10000	0	0
MAP2K1	0.03	0.02	-9999	-10000	0	0
MAP2K7	0.014	0	-9999	-10000	0	0
KLRG1/SHP2	-0.081	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	-0.56	5	5
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	23	23
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	-0.51	13	13
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

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.58	21	21
PLCG1	-0.015	0.13	-9999	-0.48	11	11
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	12	12
negative regulation of cAMP metabolic process	-0.015	0.13	-9999	-0.5	11	11
MAPK3	-0.023	0.17	-9999	-0.51	23	23
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.01	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	-0.51	23	23
S1P1/S1P/PDGFB-D/PDGFRB	-0.059	0.18	-9999	-0.57	18	18
ABCC1	0.008	0.065	-9999	-0.82	3	3

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.032	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	-0.67	2	2
CBL	0.014	0	-9999	-10000	0	0
mol:NO	-0.016	0.17	-9999	-0.64	2	2
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	-0.6	2	2
mol:Ca2+	-0.055	0.2	-9999	-0.48	93	93
MAPK3	-0.035	0.18	-9999	-0.58	2	2
MAPK1	-0.035	0.18	-9999	-0.58	2	2
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	-0.56	3	3
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	-0.64	2	2
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	-0.64	2	2
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

×

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	-0.53	61	61
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

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.002	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

×

Noncanonical Wnt signaling pathway

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	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	-0.65	11	11
mol:DAG	-0.009	0.14	-9999	-0.7	6	6
PLCG1	-0.01	0.14	-9999	-0.74	6	6
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	-0.75	6	6
MAP3K7	-0.057	0.17	-9999	-0.68	7	7
mol:Ca2+	-0.008	0.13	-9999	-0.67	6	6
mol:IP3	-0.009	0.14	-9999	-0.7	6	6
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.014	0	-9999	-10000	0	0
CAMK2A	-0.07	0.18	-9999	-0.56	21	21
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	-0.68	6	6
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	-0.62	17	17
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

×

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	19	19
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

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.3	14	14
CDC42/GDP	0.038	0.088	-9999	-0.39	14	14
Rac1/GDP	0.04	0.087	-9999	-0.39	14	14
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	-0.42	3	3
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	-0.42	28	28
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	-0.3	14	14
alphaV/beta3 Integrin/Talin	0.017	0.11	-9999	-0.42	22	22
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	-0.51	3	3
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.014	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.007	0.037	0.25	7	-10000	0	7
RFC1	0.007	0.037	0.25	7	-10000	0	7
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	0.22	9	-0.3	87	96
MAP2K4	-0.007	0.13	-10000	0	-0.42	12	12
mol:ceramide	-0.029	0.14	-10000	0	-0.48	13	13
GSN	0.007	0.037	0.25	7	-10000	0	7
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	5	-0.33	2	7
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	0.25	7	-10000	0	7
FADD	-0.085	0.27	-10000	0	-0.82	59	59
actin filament polymerization	-0.007	0.037	-10000	0	-0.25	7	7
NFKB1	-0.031	0.061	-10000	0	-10000	0	0
MAPK8	-0.014	0.16	-10000	0	-0.56	10	10
DFFA	0.007	0.037	0.26	5	-10000	0	5
DNA fragmentation during apoptosis	0.005	0.046	0.25	7	-0.43	2	9
FAS/FADD/MET	-0.071	0.19	-10000	0	-0.55	63	63
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	0.25	7	-0.43	2	9
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	0.25	7	-10000	0	7
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

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.37	4	6
RAR alpha/9cRA/Cyclin H	-0.023	0.06	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.002	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	-0.46	9	9
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	-0.55	26	26
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	-0.42	15	15
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.017	0.15	-10000	0	-0.51	14	14
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 S78. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.21	-9999	-0.64	6	6
CRP	-0.031	0.24	-9999	-0.73	21	21
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	-0.71	44	44
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	16	16
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	-0.56	10	10
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	-0.47	2	2
STAT3	-0.024	0.24	-9999	-0.71	12	12
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	16	16
STAT3 (dimer)/FOXO1	0.031	0.2	-9999	-0.55	1	1
GRB2/SOS1/GAB family	-0.047	0.1	-9999	-0.53	7	7
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.02	0.15	-9999	-0.55	18	18
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	-0.66	3	3
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	-0.63	4	4
FOS	-0.061	0.19	-9999	-0.57	64	64
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.024	0.16	-9999	-0.54	19	19
STAT1/PIAS1	-0.022	0.15	-9999	-0.52	13	13
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	-0.96	2	2
gp130 (dimer)/JAK1/JAK1/LMO4	-0.015	0.12	-9999	-10000	0	0
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	-0.67	44	44
IRF1	-0.012	0.21	-9999	-0.66	3	3
mol:GDP	-0.019	0.16	-9999	-0.55	19	19
SOS1	0.013	0.004	-9999	-10000	0	0
VAV1	-0.02	0.16	-9999	-0.56	19	19
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	-0.54	19	19
LMO4	0.016	0.011	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.1	0.16	-9999	-0.68	11	11
MCL1	0.063	0.028	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
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	-0.45	134	134
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	-0.42	1	1
Ephrin A1/EPHA2	-0.008	0.051	-9999	-0.49	3	3
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

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

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	-0.41	16	16
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	-0.5	9	9
FOXO3	0.062	0.1	-10000	0	-0.59	2	2
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	-0.53	10	10
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	-0.51	10	10
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	-0.4	59	59
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

×

Rapid glucocorticoid signaling

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

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	5	5
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	-1.1	13	13
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	-1.2	7	7
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	-1.4	4	4
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	-1.2	5	5
FOXM1B/HNF6	0.093	0.42	-9999	-1.4	10	10
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	-1.5	3	3
CCNB2	0.15	0.32	-9999	-1.4	3	3
CCNB1	0.16	0.33	-9999	-1.3	3	3
ETV5	0.15	0.32	-9999	-1.2	3	3
ESR1	0.12	0.38	-9999	-1.2	11	11
CCND1	0.1	0.38	-9999	-1.2	7	7
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	7	7
MMP2	0.11	0.38	-9999	-1.1	9	9
RB1/FOXM1C	0.12	0.36	-9999	-1.2	5	5
CREBBP	0.014	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.001	0.16	-9999	-0.58	14	14
MAP3K8	0.009	0.045	-9999	-0.57	3	3
FOS	0.009	0.12	-9999	-0.49	13	13
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	-0.38	11	11
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	-0.37	10	10
mol:GTP	-0.001	0.002	-9999	-0.006	64	64
MAPK1	0.012	0.083	-9999	-0.38	11	11
RAF1	-0.01	0.052	-9999	-0.37	10	10
KRAS	0.01	0.053	-9999	-0.82	2	2

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.031	0.047	-9999	-10000	0	0
STMN1	0.012	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	-0.5	14	14
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	-0.26	8	8
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	-0.35	8	8
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	-0.45	4	4
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

×

RXR and RAR heterodimerization with other nuclear receptor

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
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	-0.49	4	4
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	-0.48	8	8
RXRs/PPAR	-0.095	0.16	-9999	-0.49	17	17
NCOR2	0.014	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.026	-9999	-0.42	2	2
RARs/VDR/DNA/Vit D3	-0.026	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	-0.46	11	11
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	-0.48	4	4
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	-0.48	9	9
BCL2	0.002	0.09	-9999	-0.69	8	8

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.011	0.037	-9999	-0.57	2	2
Caspase 8 (4 units)	-0.037	0.078	-9999	-0.45	5	5
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	-0.42	5	5
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	-0.49	9	9
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	-0.53	4	4
APAF-1/Caspase 9	-0.042	0.1	-9999	-0.44	22	22
BCL2	0.013	0.11	-9999	-0.43	9	9

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.14	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	-0.52	3	3
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	-0.57	5	5
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

×

Circadian rhythm pathway

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

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.071	-10000	0	-0.63	6	6
MAP4K4	0.029	0.082	-10000	0	-0.43	3	3
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	59	59
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	0.2	2	-10000	0	2
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	0.22	2	-10000	0	2
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 S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.43	7	7
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 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
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

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.81	6	6
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	-0.89	5	5
FXN	-0.022	0.23	-10000	0	-0.8	6	6
POU5F1	-0.047	0.28	-10000	0	-0.84	22	22
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	-0.85	15	15
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	8	8
VEGFA	-0.025	0.25	-10000	0	-0.89	10	10
CREBBP	0.014	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
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	-0.42	12	12
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 S95. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.32	8	8
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

×

IGF1 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
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	-0.49	4	4
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	-0.45	5	5
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	-0.36	81	81
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	-0.45	5	5
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	-0.54	7	7
SHC1	0.014	0	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.046	0.11	-9999	-0.6	4	4
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	-10000	0	0
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	-10000	0	0
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	-10000	0	0
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	-0.47	2	2
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 S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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

×

Signaling events mediated by VEGFR1 and VEGFR2

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
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	-0.61	3	3
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	-0.5	12	12
endothelial cell proliferation	0.094	0.063	-9999	-0.46	1	1
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	-0.46	8	8
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	-0.64	2	2
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	-0.54	2	2
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	-0.34	1	1
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	-0.49	2	2
MAPK1	0.057	0.066	-9999	-0.49	2	2
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	-0.5	2	2
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	-0.54	2	2
PRKACA	0.014	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.072	0.18	-9999	-0.5	70	70
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	-0.46	8	8
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	-0.66	2	2
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	-0.66	2	2
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	-0.5	9	9
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

×

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

×

Hedgehog signaling events mediated by Gli proteins

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
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	-0.46	24	24
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	-0.46	24	24
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	-0.46	24	24
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	-0.33	16	16
KIF3A	0.014	0	-9999	-10000	0	0
GLI1	-0.024	0.16	-9999	-0.47	24	24
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	-0.42	2	2
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	-0.63	24	24
CREBBP	-0.024	0.12	-9999	-0.34	2	2
Su(fu)/SIN3/HDAC complex	0.051	0.02	-9999	-10000	0	0

×

Aurora A signaling

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
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	11	11
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	-0.35	11	11
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	-0.36	63	63
Aurora A/CPEB	-0.05	0.13	-9999	-0.36	63	63
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	11	11
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	-0.35	1	1
OAZ1	0.014	0	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.014	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.024	-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

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.39	3	-10000	0	3
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	-0.45	3	3
MAPK3	0.013	0.069	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.018	0.065	-10000	0	-0.4	3	3
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	-0.3	3	3
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	-0.45	3	3
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	-0.45	3	3
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	-0.45	3	3

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.007	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	-10000	0	0
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	-10000	0	0
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

×

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	-0.51	14	14
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

×

Regulation of p38-alpha and p38-beta

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
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	-0.36	5	5
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	-0.38	4	4
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 S109. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	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	-0.3	1	1
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	-0.38	3	3
HCK	0.006	0.079	-9999	-0.77	5	5
CYTH3	-0.002	0.029	-9999	-0.38	3	3
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	-0.3	1	1
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	-0.44	10	10
LCK	-0.006	0.13	-9999	-0.82	12	12
BTK	-0.004	0.04	-9999	-0.43	2	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.25	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	-10000	0	0
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	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.014	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.014	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.025	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	-0.44	2	2
EXOC6	0.014	0	-10000	0	-10000	0	0
PLD1	-0.002	0.021	-10000	0	-0.28	3	3
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.014	0	-10000	0	-10000	0	0
PIP5K1C	0.035	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 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
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	-0.022	4	15
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	-10000	0	0
PPP1R12A	0.014	0.001	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
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	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.031	-10000	0	-0.38	1	1
microtubule-based process	0.023	0.019	-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

×

ceramide signaling pathway

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
MAP4K4	0.035	0.082	-10000	0	-0.41	5	5
BAG4	0.011	0.037	-10000	0	-0.57	2	2
BAD	0.029	0.03	-10000	0	-10000	0	0
NFKBIA	0.012	0.037	-10000	0	-0.82	1	1
BIRC3	-0.022	0.17	-10000	0	-0.82	21	21
BAX	0.029	0.03	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.022	-10000	0	-0.095	9	9
IKBKB	0.042	0.078	-10000	0	-10000	0	0
MAP2K2	0.041	0.032	-10000	0	-10000	0	0
MAP2K1	0.041	0.032	-10000	0	-10000	0	0
SMPD1	0.018	0.022	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.012	0.17	-10000	0	-0.65	7	7
MAP2K4	0.036	0.03	-10000	0	-10000	0	0
protein ubiquitination	0.043	0.079	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.046	0.035	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.036	0.032	-10000	0	-10000	0	0
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.022	0.031	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.001	0.025	-10000	0	-0.55	1	1
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.029	0.031	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.014	0	-10000	0	-10000	0	0
MAPK3	0.044	0.031	-10000	0	-10000	0	0
MAPK1	0.044	0.031	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	-0.001	0.028	-10000	0	-0.63	1	1
FADD	-0.021	0.18	-10000	0	-0.44	64	64
KSR1	0.029	0.031	-10000	0	-10000	0	0
MAPK8	0.038	0.044	-10000	0	-0.31	1	1
TRAF2	0.002	0.098	-10000	0	-0.82	7	7
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.042	0.078	-10000	0	-10000	0	0
TNF R/SODD	-0.001	0.026	-10000	0	-0.41	2	2
TNF	-0.025	0.17	-10000	0	-0.79	24	24
CYCS	0.032	0.031	0.14	3	-10000	0	3
IKBKG	0.042	0.078	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.085	-10000	0	-0.43	9	9
RELA	0.014	0	-10000	0	-10000	0	0
RIPK1	0.014	0	-10000	0	-10000	0	0
AIFM1	0.032	0.031	0.14	3	-10000	0	3
TNF/TNF R/SODD	-0.026	0.11	-10000	0	-0.54	21	21
TNFRSF1A	0.014	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.022	-10000	0	-10000	0	0
NSMAF	0.035	0.081	-10000	0	-0.41	5	5
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.002	0.09	-10000	0	-0.69	8	8

×

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	-0.44	24	24
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	-0.36	4	4
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	0.35	4	-10000	0	4
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	-0.45	24	24
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	-0.17	1	1
AKT2	0.014	0	-9999	-10000	0	0
PTEN	0.014	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.049	0.04	-10000	0	-10000	0	0
adherens junction organization	0.037	0.057	-10000	0	-0.53	3	3
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	-0.38	2	2
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	-0.47	6	6
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	-0.37	2	2
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	-0.38	2	2
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	-0.42	16	16
PIP5K1A	0.042	0.047	-10000	0	-0.57	2	2
PLCG1	-0.004	0.033	-10000	0	-0.39	2	2
Rac1/GTP	-0.018	0.082	-10000	0	-0.42	17	17
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.005	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 S117. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0.006	-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 S118. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	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	-0.51	28	28
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 S119. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.011	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

×

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	-10000	0	0
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	-0.29	25	25
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	-0.41	6	6
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	-0.45	1	1
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