PARADIGM pathway analysis of mRNASeq expression data - Kidney Renal Clear Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	365
HIF-1-alpha transcription factor network	202
Nephrin/Neph1 signaling in the kidney podocyte	179
TCR signaling in naïve CD8+ T cells	141
TCGA08_p53	139
Syndecan-4-mediated signaling events	117
Aurora B signaling	115
FOXA2 and FOXA3 transcription factor networks	110
Glypican 1 network	108
FOXM1 transcription factor network	105

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	0.7213	365	2924	8	-0.84	0.22	1000	-1000	-0.032	-1000
HIF-1-alpha transcription factor network	0.3992	202	15410	76	-1.3	0.026	1000	-1000	-0.16	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3538	179	6089	34	-0.61	0.016	1000	-1000	-0.098	-1000
TCR signaling in naïve CD8+ T cells	0.2787	141	13205	93	-0.66	0.33	1000	-1000	-0.12	-1000
TCGA08_p53	0.2747	139	975	7	-0.65	0.31	1000	-1000	-0.024	-1000
Syndecan-4-mediated signaling events	0.2312	117	7840	67	-0.65	0.11	1000	-1000	-0.13	-1000
Aurora B signaling	0.2273	115	7712	67	-0.41	0.016	1000	-1000	-0.1	-1000
FOXA2 and FOXA3 transcription factor networks	0.2174	110	5096	46	-1.2	0.025	1000	-1000	-0.1	-1000
Glypican 1 network	0.2134	108	5193	48	-0.56	0.045	1000	-1000	-0.068	-1000
FOXM1 transcription factor network	0.2075	105	5388	51	-0.82	0.04	1000	-1000	-0.2	-1000
IL12-mediated signaling events	0.2016	102	8881	87	-0.7	0.16	1000	-1000	-0.16	-1000
PDGFR-alpha signaling pathway	0.1976	100	4419	44	-0.28	0.034	1000	-1000	-0.087	-1000
amb2 Integrin signaling	0.1621	82	6784	82	-0.56	0.016	1000	-1000	-0.12	-1000
JNK signaling in the CD4+ TCR pathway	0.1443	73	1254	17	-0.41	0.016	1000	-1000	-0.1	-1000
IL4-mediated signaling events	0.1383	70	6370	91	-0.84	0.54	1000	-1000	-0.19	-1000
EGFR-dependent Endothelin signaling events	0.1383	70	1489	21	-0.67	0.016	1000	-1000	-0.11	-1000
Aurora C signaling	0.1364	69	483	7	-0.4	0.012	1000	-1000	-0.061	-1000
Syndecan-1-mediated signaling events	0.1304	66	2274	34	-0.42	0.016	1000	-1000	-0.098	-1000
Glypican 2 network	0.1304	66	266	4	-0.12	-1000	1000	-1000	-0.058	-1000
HIF-2-alpha transcription factor network	0.1285	65	2804	43	-0.76	0.33	1000	-1000	-0.11	-1000
Caspase cascade in apoptosis	0.1245	63	4694	74	-0.32	0.16	1000	-1000	-0.078	-1000
VEGFR1 specific signals	0.1245	63	3578	56	-0.47	0.045	1000	-1000	-0.12	-1000
IL23-mediated signaling events	0.1146	58	3539	60	-0.4	0.021	1000	-1000	-0.19	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1126	57	1905	33	-0.83	0.016	1000	-1000	-0.09	-1000
BMP receptor signaling	0.1087	55	4526	81	-0.7	0.016	1000	-1000	-0.13	-1000
Signaling events mediated by the Hedgehog family	0.0968	49	2578	52	-0.44	0.12	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	0.0850	43	4205	97	-0.33	0.04	1000	-1000	-0.14	-1000
IL27-mediated signaling events	0.0830	42	2142	51	-0.61	0.076	1000	-1000	-0.13	-1000
Effects of Botulinum toxin	0.0791	40	1056	26	-0.37	0.016	1000	-1000	-0.088	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0791	40	2720	68	-0.55	0.063	1000	-1000	-0.17	-1000
S1P1 pathway	0.0771	39	1427	36	-0.37	0.018	1000	-1000	-0.1	-1000
Ephrin A reverse signaling	0.0751	38	267	7	-0.056	0	1000	-1000	-0.05	-1000
Arf6 signaling events	0.0731	37	2323	62	-0.67	0.016	1000	-1000	-0.084	-1000
Calcium signaling in the CD4+ TCR pathway	0.0731	37	1151	31	-0.46	0.016	1000	-1000	-0.16	-1000
p75(NTR)-mediated signaling	0.0672	34	4314	125	-0.42	0.016	1000	-1000	-0.15	-1000
IL2 signaling events mediated by STAT5	0.0672	34	750	22	-0.45	0.038	1000	-1000	-0.06	-1000
IL2 signaling events mediated by PI3K	0.0652	33	1934	58	-0.44	0.031	1000	-1000	-0.12	-1000
LPA4-mediated signaling events	0.0632	32	394	12	-0.16	0.026	1000	-1000	-0.038	-1000
PLK1 signaling events	0.0593	30	2582	85	-0.39	0.016	1000	-1000	-0.08	-1000
BCR signaling pathway	0.0593	30	3034	99	-0.33	0.034	1000	-1000	-0.13	-1000
Coregulation of Androgen receptor activity	0.0573	29	2219	76	-0.92	0.033	1000	-1000	-0.082	-1000
IL6-mediated signaling events	0.0553	28	2118	75	-0.28	0.076	1000	-1000	-0.12	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0534	27	1465	54	-0.65	0.031	1000	-1000	-0.13	-1000
EPO signaling pathway	0.0534	27	1485	55	-0.29	0.018	1000	-1000	-0.14	-1000
Regulation of Telomerase	0.0534	27	2829	102	-0.67	0.051	1000	-1000	-0.16	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0534	27	2149	78	-0.31	0.045	1000	-1000	-0.1	-1000
Glucocorticoid receptor regulatory network	0.0514	26	3048	114	-0.41	0.16	1000	-1000	-0.093	-1000
Integrins in angiogenesis	0.0514	26	2206	84	-0.37	0.039	1000	-1000	-0.13	-1000
Aurora A signaling	0.0455	23	1434	60	-0.25	0.053	1000	-1000	-0.082	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0455	23	2052	88	-0.32	0.074	1000	-1000	-0.14	-1000
Visual signal transduction: Rods	0.0455	23	1199	52	-0.28	0.016	1000	-1000	-0.11	-1000
Signaling events mediated by PTP1B	0.0435	22	1713	76	-0.67	0.049	1000	-1000	-0.12	-1000
Reelin signaling pathway	0.0435	22	1246	56	-0.24	0.016	1000	-1000	-0.12	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0415	21	974	45	-0.57	0.061	1000	-1000	-0.12	-1000
Syndecan-2-mediated signaling events	0.0395	20	1389	69	-0.56	0.055	1000	-1000	-0.087	-1000
Endothelins	0.0375	19	1828	96	-0.35	0.088	1000	-1000	-0.11	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0375	19	2314	120	-0.17	0.14	1000	-1000	-0.13	-1000
Wnt signaling	0.0336	17	122	7	-0.071	0.016	1000	-1000	-0.079	-1000
Regulation of nuclear SMAD2/3 signaling	0.0316	16	2305	136	-0.45	0.095	1000	-1000	-0.11	-1000
Thromboxane A2 receptor signaling	0.0316	16	1783	105	-0.67	0.066	1000	-1000	-0.11	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0316	16	605	37	-0.29	0.025	1000	-1000	-0.11	-1000
S1P3 pathway	0.0316	16	672	42	-0.37	0.062	1000	-1000	-0.081	-1000
Presenilin action in Notch and Wnt signaling	0.0296	15	973	61	-0.18	0.091	1000	-1000	-0.1	-1000
LPA receptor mediated events	0.0296	15	1599	102	-0.41	0.061	1000	-1000	-0.14	-1000
PLK2 and PLK4 events	0.0277	14	42	3	-0.016	0.01	1000	-1000	-0.031	-1000
Ceramide signaling pathway	0.0277	14	1107	76	-0.67	0.23	1000	-1000	-0.095	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0257	13	384	28	-0.13	0.025	1000	-1000	-0.081	-1000
FoxO family signaling	0.0257	13	867	64	-0.57	0.12	1000	-1000	-0.11	-1000
FAS signaling pathway (CD95)	0.0257	13	625	47	-0.43	0.029	1000	-1000	-0.071	-1000
Class I PI3K signaling events	0.0257	13	977	73	-0.45	0.036	1000	-1000	-0.1	-1000
E-cadherin signaling events	0.0257	13	68	5	-0.023	0.016	1000	-1000	-0.061	-1000
ErbB4 signaling events	0.0237	12	833	69	-0.18	0.1	1000	-1000	-0.12	-1000
IFN-gamma pathway	0.0237	12	840	68	-0.38	0.017	1000	-1000	-0.14	-1000
Canonical Wnt signaling pathway	0.0237	12	662	51	-0.18	0.094	1000	-1000	-0.097	-1000
Nongenotropic Androgen signaling	0.0237	12	633	52	-0.17	0.071	1000	-1000	-0.091	-1000
Regulation of Androgen receptor activity	0.0237	12	860	70	-0.96	0.04	1000	-1000	-0.099	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0217	11	1405	125	-0.39	0.043	1000	-1000	-0.15	-1000
S1P5 pathway	0.0198	10	177	17	-0.13	0.043	1000	-1000	-0.081	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0198	10	771	74	-0.67	0.099	1000	-1000	-0.13	-1000
Visual signal transduction: Cones	0.0178	9	342	38	-0.041	0.016	1000	-1000	-0.1	-1000
Noncanonical Wnt signaling pathway	0.0178	9	250	26	-0.11	0.016	1000	-1000	-0.14	-1000
a4b1 and a4b7 Integrin signaling	0.0178	9	45	5	-0.02	0.016	1000	-1000	-0.054	-1000
S1P4 pathway	0.0178	9	249	25	-0.13	0.035	1000	-1000	-0.081	-1000
TCGA08_rtk_signaling	0.0158	8	229	26	-0.28	0.041	1000	-1000	-0.032	-1000
Signaling events regulated by Ret tyrosine kinase	0.0138	7	649	82	-0.064	0.027	1000	-1000	-0.12	-1000
Canonical NF-kappaB pathway	0.0119	6	260	39	-0.19	0.075	1000	-1000	-0.12	-1000
Signaling events mediated by PRL	0.0119	6	213	34	-0.058	0.046	1000	-1000	-0.084	-1000
Class IB PI3K non-lipid kinase events	0.0119	6	18	3	-0.006	0.006	1000	-1000	-0.015	-1000
p38 MAPK signaling pathway	0.0119	6	264	44	-0.1	0.049	1000	-1000	-0.091	-1000
ErbB2/ErbB3 signaling events	0.0099	5	379	65	-0.14	0.059	1000	-1000	-0.11	-1000
Insulin-mediated glucose transport	0.0099	5	177	32	-0.086	0.066	1000	-1000	-0.088	-1000
Signaling events mediated by HDAC Class III	0.0099	5	224	40	-0.06	0.031	1000	-1000	-0.082	-1000
IL1-mediated signaling events	0.0099	5	370	62	-0.093	0.061	1000	-1000	-0.15	-1000
Ephrin B reverse signaling	0.0099	5	279	48	-0.027	0.032	1000	-1000	-0.11	-1000
Signaling mediated by p38-gamma and p38-delta	0.0099	5	81	15	0	0.037	1000	-1000	-0.056	-1000
Syndecan-3-mediated signaling events	0.0099	5	177	35	-0.04	0.016	1000	-1000	-0.11	-1000
E-cadherin signaling in the nascent adherens junction	0.0099	5	389	76	-0.026	0.067	1000	-1000	-0.11	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0079	4	365	85	-0.035	0.079	1000	-1000	-0.11	-1000
Arf6 downstream pathway	0.0079	4	214	43	-0.033	0.033	1000	-1000	-0.065	-1000
Paxillin-dependent events mediated by a4b1	0.0079	4	155	36	-0.027	0.031	1000	-1000	-0.096	-1000
EPHB forward signaling	0.0079	4	345	85	-0.073	0.07	1000	-1000	-0.14	-1000
Ras signaling in the CD4+ TCR pathway	0.0079	4	80	17	-0.037	0.055	1000	-1000	-0.076	-1000
BARD1 signaling events	0.0059	3	223	57	-0.17	0.043	1000	-1000	-0.11	-1000
Cellular roles of Anthrax toxin	0.0059	3	119	39	-0.022	0.027	1000	-1000	-0.043	-1000
Plasma membrane estrogen receptor signaling	0.0059	3	324	86	-0.17	0.072	1000	-1000	-0.12	-1000
E-cadherin signaling in keratinocytes	0.0059	3	134	43	-0.29	0.053	1000	-1000	-0.12	-1000
Osteopontin-mediated events	0.0040	2	107	38	-0.03	0.099	1000	-1000	-0.14	-1000
Hedgehog signaling events mediated by Gli proteins	0.0040	2	131	65	-0.063	0.093	1000	-1000	-0.089	-1000
ceramide signaling pathway	0.0040	2	138	49	-0.12	0.054	1000	-1000	-0.063	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0040	2	128	52	-0.031	0.092	1000	-1000	-0.093	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0040	2	174	83	-0.086	0.081	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class I	0.0040	2	210	104	-0.03	0.064	1000	-1000	-0.11	-1000
Regulation of p38-alpha and p38-beta	0.0040	2	156	54	-0.04	0.073	1000	-1000	-0.078	-1000
Arf6 trafficking events	0.0040	2	175	71	-0.13	0.058	1000	-1000	-0.11	-1000
IGF1 pathway	0.0040	2	119	57	-0.066	0.071	1000	-1000	-0.14	-1000
Insulin Pathway	0.0040	2	192	74	-0.035	0.055	1000	-1000	-0.14	-1000
PDGFR-beta signaling pathway	0.0040	2	232	97	-0.055	0.087	1000	-1000	-0.14	-1000
Signaling events mediated by HDAC Class II	0.0020	1	121	75	-0.027	0.051	1000	-1000	-0.094	-1000
Circadian rhythm pathway	0.0020	1	29	22	-0.019	0.065	1000	-1000	-0.091	-1000
mTOR signaling pathway	0.0020	1	62	53	-0.007	0.044	1000	-1000	-0.085	-1000
Class I PI3K signaling events mediated by Akt	0.0020	1	89	68	-0.086	0.06	1000	-1000	-0.11	-1000
Nectin adhesion pathway	0.0020	1	63	63	-0.016	0.08	1000	-1000	-0.1	-1000
Retinoic acid receptors-mediated signaling	0.0020	1	114	58	-0.025	0.063	1000	-1000	-0.11	-1000
Atypical NF-kappaB pathway	0.0020	1	52	31	-0.022	0.036	1000	-1000	-0.1	-1000
Signaling mediated by p38-alpha and p38-beta	0.0020	1	52	44	-0.042	0.051	1000	-1000	-0.089	-1000
Alternative NF-kappaB pathway	0.0020	1	14	13	-0.005	0.016	1000	-1000	-0.09	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	2	23	-0.001	0.062	1000	-1000	-0.11	-1000
TRAIL signaling pathway	0.0000	0	25	48	-0.002	0.071	1000	-1000	-0.1	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.082	-1000
Rapid glucocorticoid signaling	0.0000	0	11	20	-0.005	0.016	1000	-1000	-0.059	-1000
Arf1 pathway	0.0000	0	29	54	-0.009	0.044	1000	-1000	-0.064	-1000
Total	NA	4080	212932	7203	-40	-990	131000	-131000	-14	-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	-0.01	0.094	-10000	0	-0.87	6	6
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.84	0.17	-10000	0	-0.87	487	487
CCND2	0.18	0.048	0.19	486	-10000	0	486
RB1	-0.2	0.05	-10000	0	-0.21	486	486
CDK4	0.22	0.051	0.22	486	-10000	0	486
CDK6	0.2	0.054	0.21	486	-0.18	1	487
G1/S progression	0.2	0.054	0.21	486	-10000	0	486

×

HIF-1-alpha transcription factor network

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
PKM2	-0.97	0.53	-9999	-1.3	316	316
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.91	299	299
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.97	0.53	-9999	-1.3	315	315
AP1	-0.015	0.09	-9999	-0.57	13	13
ABCG2	-0.97	0.53	-9999	-1.3	307	307
HIF1A	-0.1	0.069	-9999	-0.9	2	2
TFF3	-0.98	0.54	-9999	-1.3	309	309
GATA2	-0.001	0.12	-9999	-0.74	12	12
AKT1	-0.093	0.053	-9999	-10000	0	0
response to hypoxia	-0.12	0.058	-9999	-10000	0	0
MCL1	-0.97	0.53	-9999	-1.3	315	315
NDRG1	-0.97	0.53	-9999	-1.3	307	307
SERPINE1	-1	0.57	-9999	-1.4	316	316
FECH	-0.97	0.53	-9999	-1.3	307	307
FURIN	-0.97	0.53	-9999	-1.3	308	308
NCOA2	-0.001	0.095	-9999	-0.75	8	8
EP300	-0.099	0.075	-9999	-0.39	3	3
HMOX1	-0.99	0.55	-9999	-1.4	309	309
BHLHE40	-0.97	0.53	-9999	-1.3	316	316
BHLHE41	-1.1	0.58	-9999	-1.4	318	318
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.079	0.057	-9999	-0.6	2	2
ENG	-0.058	0.063	-9999	-10000	0	0
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.97	0.53	-9999	-1.3	319	319
ABCB1	-0.3	0.42	-9999	-1.3	67	67
TFRC	-0.97	0.53	-9999	-1.3	315	315
CXCR4	-1.1	0.6	-9999	-1.5	316	316
TF	-1	0.58	-9999	-1.4	302	302
CITED2	-0.97	0.53	-9999	-1.3	308	308
HIF1A/ARNT	-1.3	0.86	-9999	-1.7	328	328
LDHA	-0.085	0.063	-9999	-0.85	2	2
ETS1	-0.97	0.53	-9999	-1.3	307	307
PGK1	-0.97	0.53	-9999	-1.3	308	308
NOS2	-0.98	0.53	-9999	-1.3	309	309
ITGB2	-1	0.57	-9999	-1.4	324	324
ALDOA	-0.97	0.53	-9999	-1.3	308	308
Cbp/p300/CITED2	-0.97	0.54	-9999	-1.4	290	290
FOS	-0.003	0.12	-9999	-0.75	13	13
HK2	-1.2	0.59	-9999	-1.5	378	378
SP1	0.021	0.03	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.1	10	10
HK1	-0.97	0.53	-9999	-1.3	318	318
NPM1	-0.97	0.53	-9999	-1.3	308	308
EGLN1	-0.97	0.53	-9999	-1.3	307	307
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.97	0.53	-9999	-1.3	319	319
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.091	0.17	-9999	-0.8	18	18
IGFBP1	-1	0.58	-9999	-1.4	314	314
VEGFA	-0.77	0.41	-9999	-1.1	231	231
HIF1A/JAB1	-0.054	0.048	-9999	-0.7	2	2
CP	-1.2	0.59	-9999	-1.5	370	370
CXCL12	-0.98	0.53	-9999	-1.3	320	320
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.97	0.53	-9999	-1.3	307	307
EGLN3	-1.3	0.51	-9999	-1.5	394	394
CA9	-1.3	0.48	-9999	-1.5	404	404
TERT	-1	0.55	-9999	-1.4	307	307
ENO1	-0.97	0.53	-9999	-1.3	307	307
PFKL	-0.97	0.53	-9999	-1.3	308	308
NCOA1	0.015	0.003	-9999	-10000	0	0
ADM	-1	0.57	-9999	-1.4	321	321
ARNT	-0.099	0.047	-9999	-10000	0	0
HNF4A	-0.045	0.22	-9999	-0.75	43	43
ADFP	-0.98	0.53	-9999	-1.3	321	321
SLC2A1	-0.62	0.34	-9999	-0.97	168	168
LEP	-1	0.55	-9999	-1.4	324	324
HIF1A/ARNT/Cbp/p300	-0.7	0.34	-9999	-0.93	301	301
EPO	-0.61	0.39	-9999	-1.1	176	176
CREBBP	-0.098	0.073	-9999	-0.35	5	5
HIF1A/ARNT/Cbp/p300/HDAC7	-0.74	0.39	-9999	-1	305	305
PFKFB3	-0.97	0.53	-9999	-1.3	319	319
NT5E	-0.97	0.53	-9999	-1.3	307	307

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.48	0.26	0.62	392	-10000	0	392
KIRREL	-0.054	0.1	-10000	0	-0.82	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.49	0.26	-10000	0	-0.62	392	392
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.039	-10000	0	-0.86	1	1
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.53	0.31	-10000	0	-0.84	219	219
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.41	0.26	-10000	0	-0.67	219	219
FYN	-0.5	0.3	-10000	0	-0.8	219	219
mol:Ca2+	-0.52	0.31	-10000	0	-0.83	219	219
mol:DAG	-0.53	0.31	-10000	0	-0.84	219	219
NPHS2	-0.41	0.38	-10000	0	-0.81	244	244
mol:IP3	-0.53	0.31	-10000	0	-0.84	219	219
regulation of endocytosis	-0.47	0.28	-10000	0	-0.75	219	219
Nephrin/NEPH1/podocin/Cholesterol	-0.54	0.31	-10000	0	-0.65	419	419
establishment of cell polarity	-0.48	0.26	-10000	0	-0.62	392	392
Nephrin/NEPH1/podocin/NCK1-2	-0.49	0.29	-10000	0	-0.79	219	219
Nephrin/NEPH1/beta Arrestin2	-0.48	0.29	-10000	0	-0.77	219	219
NPHS1	-0.61	0.33	-10000	0	-0.79	390	390
Nephrin/NEPH1/podocin	-0.51	0.3	-10000	0	-0.81	219	219
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.014	0.034	-10000	0	-0.75	1	1
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.53	0.31	-10000	0	-0.84	219	219
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.53	0.31	-10000	0	-0.84	219	219
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.49	0.3	-10000	0	-0.79	219	219
cytoskeleton organization	-0.53	0.32	-10000	0	-0.85	219	219
Nephrin/NEPH1	-0.36	0.2	-10000	0	-0.47	392	392
Nephrin/NEPH1/ZO-1	-0.39	0.22	-10000	0	-0.51	392	392

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.34	0.33	-10000	0	-0.68	231	231
FYN	-0.41	0.5	-10000	0	-0.92	235	235
LAT/GRAP2/SLP76	-0.36	0.39	-10000	0	-0.75	234	234
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.25	0.29	-10000	0	-0.54	235	235
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.08	0.072	-10000	0	-0.19	81	81
MAP3K8	0.012	0.055	-10000	0	-0.86	2	2
mol:Ca2+	-0.11	0.045	-10000	0	-0.14	286	286
integrin-mediated signaling pathway	-0.018	0.1	-10000	0	-0.58	16	16
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.41	0.45	-10000	0	-0.85	245	245
TRPV6	-0.66	0.26	-10000	0	-0.76	438	438
CD28	-0.057	0.23	-10000	0	-0.87	38	38
SHC1	-0.44	0.49	-10000	0	-0.93	238	238
receptor internalization	-0.51	0.56	-10000	0	-1.1	240	240
PRF1	-0.48	0.6	-10000	0	-1.1	234	234
KRAS	0.016	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.18	0.22	-10000	0	-0.41	216	216
LAT	-0.5	0.53	-10000	0	-1	251	251
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	228	228
CD3E	-0.34	0.44	-10000	0	-0.87	204	204
CD3G	-0.33	0.43	-10000	0	-0.87	199	199
RASGRP2	-0.022	0.029	-10000	0	-0.14	2	2
RASGRP1	-0.23	0.28	-10000	0	-0.51	226	226
HLA-A	0.007	0.04	-10000	0	-0.87	1	1
RASSF5	-0.012	0.15	-10000	0	-0.86	16	16
RAP1A/GTP/RAPL	-0.018	0.1	-10000	0	-0.58	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.036	0.082	-10000	0	-0.14	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.15	0.13	-10000	0	-0.34	101	101
PRKCA	-0.14	0.17	-10000	0	-0.31	177	177
GRAP2	-0.043	0.22	-10000	0	-0.86	34	34
mol:IP3	-0.16	0.34	0.26	167	-0.5	219	386
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.52	0.63	-10000	0	-1.1	241	241
ORAI1	0.33	0.13	0.38	437	-10000	0	437
CSK	-0.45	0.51	-10000	0	-0.97	237	237
B7 family/CD28	-0.52	0.52	-10000	0	-1	237	237
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.56	0.62	-10000	0	-1.2	241	241
PTPN6	-0.44	0.53	-10000	0	-0.99	229	229
VAV1	-0.48	0.53	-10000	0	-1	247	247
Monovalent TCR/CD3	-0.46	0.53	-10000	0	-1	229	229
CBL	0.014	0.034	-10000	0	-0.75	1	1
LCK	-0.44	0.53	-10000	0	-0.97	235	235
PAG1	-0.45	0.51	-10000	0	-0.97	238	238
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.53	0.63	-10000	0	-1.2	236	236
CD80	-0.19	0.37	-10000	0	-0.87	113	113
CD86	-0.13	0.32	-10000	0	-0.87	80	80
PDK1/CARD11/BCL10/MALT1	-0.18	0.17	-10000	0	-0.38	147	147
HRAS	0.014	0.039	-10000	0	-0.86	1	1
GO:0035030	-0.36	0.42	-10000	0	-0.77	237	237
CD8A	-0.39	0.44	-10000	0	-0.87	230	230
CD8B	-0.3	0.42	-10000	0	-0.87	181	181
PTPRC	-0.087	0.27	-10000	0	-0.87	55	55
PDK1/PKC theta	-0.32	0.36	-10000	0	-0.69	234	234
CSK/PAG1	-0.44	0.5	-10000	0	-0.94	235	235
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.03	-10000	0	-0.68	1	1
GRAP2/SLP76	-0.43	0.44	-10000	0	-0.88	236	236
STIM1	0.17	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.063	0.12	-10000	0	-0.25	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.59	0.66	-10000	0	-1.2	240	240
mol:DAG	-0.2	0.26	-10000	0	-0.46	231	231
RAP1A/GDP	-0.013	0.036	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.41	-10000	0	-0.87	165	165
cytotoxic T cell degranulation	-0.45	0.55	-10000	0	-1	234	234
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.31	0.35	-10000	0	-0.66	243	243
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.26	0.44	0.3	107	-0.7	230	337
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.45	0.44	-10000	0	-0.86	270	270
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.38	0.35	-10000	0	-0.73	237	237
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.5	0.56	-10000	0	-1.1	236	236
CARD11	-0.17	0.36	-10000	0	-0.86	108	108
PRKCB	-0.14	0.17	-10000	0	-0.32	186	186
PRKCE	-0.14	0.17	-10000	0	-0.31	203	203
PRKCQ	-0.39	0.42	-10000	0	-0.8	244	244
LCP2	-0.04	0.21	-10000	0	-0.86	32	32
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.2	0.24	-10000	0	-0.44	234	234
IKK complex	-0.027	0.085	-10000	0	-10000	0	0
RAS family/GDP	-0.012	0.012	-10000	0	-0.11	1	1
MAP3K14	-0.13	0.18	-10000	0	-0.32	172	172
PDPK1	-0.23	0.27	-10000	0	-0.51	227	227
TCR/CD3/MHC I/CD8/Fyn	-0.56	0.65	-10000	0	-1.2	233	233

×

TCGA08_p53

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.65	0.13	-10000	0	-0.68	487	487
TP53	-0.17	0.037	-10000	0	-10000	0	0
Senescence	-0.17	0.037	-10000	0	-10000	0	0
Apoptosis	-0.17	0.037	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.31	0.062	0.32	487	-10000	0	487
MDM4	0.014	0.039	-10000	0	-0.86	1	1

×

Syndecan-4-mediated signaling 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
PTK2	-0.055	0.14	-9999	-0.54	38	38
Syndecan-4/Syndesmos	-0.47	0.39	-9999	-0.84	231	231
positive regulation of JNK cascade	-0.54	0.37	-9999	-0.84	276	276
Syndecan-4/ADAM12	-0.57	0.5	-9999	-1	255	255
CCL5	-0.36	0.43	-9999	-0.86	215	215
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.048	0.23	-9999	-0.86	37	37
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.37	0.37	-9999	-0.72	265	265
ADAM12	-0.23	0.39	-9999	-0.86	140	140
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.1	0.071	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.48	0.4	-9999	-0.86	233	233
Syndecan-4/CXCL12/CXCR4	-0.59	0.43	-9999	-0.94	276	276
Syndecan-4/Laminin alpha3	-0.47	0.4	-9999	-0.85	236	236
MDK	-0.048	0.23	-9999	-0.86	37	37
Syndecan-4/FZD7	-0.47	0.39	-9999	-0.84	232	232
Syndecan-4/Midkine	-0.5	0.42	-9999	-0.88	242	242
FZD7	0.014	0.034	-9999	-0.75	1	1
Syndecan-4/FGFR1/FGF	-0.44	0.34	-9999	-0.77	234	234
THBS1	0.011	0.059	-9999	-0.75	3	3
integrin-mediated signaling pathway	-0.45	0.36	-9999	-0.79	236	236
positive regulation of MAPKKK cascade	-0.54	0.37	-9999	-0.84	276	276
Syndecan-4/TACI	-0.51	0.42	-9999	-0.89	244	244
CXCR4	-0.28	0.41	-9999	-0.86	170	170
cell adhesion	-0.007	0.12	-9999	-0.51	14	14
Syndecan-4/Dynamin	-0.47	0.39	-9999	-0.84	231	231
Syndecan-4/TSP1	-0.47	0.39	-9999	-0.84	233	233
Syndecan-4/GIPC	-0.47	0.39	-9999	-0.84	232	232
Syndecan-4/RANTES	-0.65	0.46	-9999	-1	285	285
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.007	0.13	-9999	-0.76	15	15
LAMA3	0.004	0.1	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.067	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.47	0.39	-9999	-0.85	232	232
TFPI	0.003	0.1	-9999	-0.8	8	8
F2	-0.32	0.42	-9999	-0.86	191	191
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.66	37	37
positive regulation of cell adhesion	-0.46	0.38	-9999	-0.82	238	238
ACTN1	0.012	0.052	-9999	-0.8	2	2
TNC	-0.002	0.12	-9999	-0.75	12	12
Syndecan-4/CXCL12	-0.48	0.4	-9999	-0.85	236	236
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.001	0.11	-9999	-0.75	11	11
TNFRSF13B	-0.071	0.26	-9999	-0.86	49	49
FGF2	0.008	0.078	-9999	-0.77	5	5
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.48	0.39	-9999	-0.85	231	231
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.04	0.23	-9999	-0.83	38	38
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.046	-9999	-0.84	1	1
vasculogenesis	-0.44	0.37	-9999	-0.79	233	233
SDC4	-0.52	0.43	-9999	-0.93	231	231
Syndecan-4/Tenascin C	-0.48	0.39	-9999	-0.84	236	236
Syndecan-4/PI-4-5-P2/PKC alpha	-0.08	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.47	0.39	-9999	-0.84	231	231
MMP9	-0.4	0.44	-9999	-0.86	243	243
Rac1/GTP	-0.008	0.12	-9999	-0.53	14	14
cytoskeleton organization	-0.44	0.36	-9999	-0.79	231	231
GIPC1	0.014	0.034	-9999	-0.75	1	1
Syndecan-4/TFPI	-0.47	0.39	-9999	-0.85	235	235

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.24	0.32	-9999	-0.68	161	161
STMN1	-0.29	0.34	-9999	-0.66	240	240
Aurora B/RasGAP/Survivin	-0.41	0.48	-9999	-0.87	246	246
Chromosomal passenger complex/Cul3 protein complex	-0.17	0.23	-9999	-0.49	147	147
BIRC5	-0.26	0.41	-9999	-0.89	151	151
DES	-0.38	0.34	-9999	-0.63	249	249
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	241	241
Aurora B/TACC1	-0.26	0.3	-9999	-0.57	240	240
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	240	240
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.073	0.09	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.41	0.5	-9999	-0.89	244	244
Cul3 protein complex	-0.015	0.083	-9999	-0.48	16	16
KIF2C	-0.16	0.18	-9999	-0.34	197	197
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.39	0.44	-9999	-0.86	232	232
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	241	241
SEPT1	-0.095	0.29	-9999	-0.86	64	64
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.18	0.24	-9999	-0.47	146	146
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.005	-9999	-10000	0	0
H3F3B	-0.17	0.21	-9999	-0.39	240	240
AURKB	-0.4	0.44	-9999	-0.87	240	240
AURKC	0.012	0.055	-9999	-0.86	2	2
CDCA8	-0.026	0.17	-9999	-0.89	19	19
cytokinesis	-0.35	0.37	-9999	-0.74	212	212
Aurora B/Septin1	-0.37	0.42	-9999	-0.83	204	204
AURKA	0.002	0.096	-9999	-0.87	6	6
INCENP	0.008	0.009	-9999	-10000	0	0
KLHL13	-0.008	0.13	-9999	-0.75	16	16
BUB1	-0.38	0.44	-9999	-0.86	225	225
hSgo1/Aurora B/Survivin	-0.4	0.49	-9999	-0.85	247	247
EVI5	0.009	0.008	-9999	-10000	0	0
RhoA/GTP	-0.31	0.34	-9999	-0.71	195	195
SGOL1	-0.016	0.16	-9999	-0.86	18	18
CENPA	-0.3	0.35	-9999	-0.63	247	247
NCAPG	-0.29	0.42	-9999	-0.86	174	174
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	240	240
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	240	240
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.14	0.33	-9999	-0.86	87	87
NPM1	-0.22	0.24	-9999	-0.47	240	240
RASA1	0.014	0.034	-9999	-0.75	1	1
KLHL9	0.016	0	-9999	-10000	0	0
mitotic prometaphase	-0.01	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.3	0.34	-9999	-0.66	240	240
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.35	0.38	-9999	-0.77	201	201
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.22	0.24	-9999	-0.47	240	240
MYLK	-0.17	0.21	-9999	-0.39	240	240
KIF23	-0.007	0.11	-9999	-0.88	8	8
VIM	-0.35	0.4	-9999	-0.73	254	254
RACGAP1	0.003	0.056	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.22	0.24	-9999	-0.47	240	240
Chromosomal passenger complex	-0.35	0.41	-9999	-0.76	234	234
Chromosomal passenger complex/EVI5	-0.37	0.48	-9999	-1	145	145
TACC1	0.016	0	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.45	0.48	-10000	0	-1.2	101	101
PCK1	-0.94	0.71	-10000	0	-1.4	306	306
HNF4A	-0.58	0.58	-10000	0	-1.4	133	133
KCNJ11	-0.45	0.51	-10000	0	-1.3	92	92
AKT1	-0.17	0.18	-10000	0	-10000	0	0
response to starvation	-0.02	0.038	-10000	0	-10000	0	0
DLK1	-0.56	0.58	-10000	0	-1.3	144	144
NKX2-1	-0.056	0.21	0.58	1	-0.84	4	5
ACADM	-0.45	0.48	-10000	0	-1.2	95	95
TAT	-0.52	0.35	-10000	0	-0.93	157	157
CEBPB	-0.024	0.14	-10000	0	-0.92	12	12
CEBPA	-0.019	0.13	-10000	0	-0.9	10	10
TTR	-0.89	0.48	-10000	0	-1.2	328	328
PKLR	-0.51	0.56	-10000	0	-1.4	117	117
APOA1	-0.56	0.56	-10000	0	-1.3	132	132
CPT1C	-0.45	0.48	-10000	0	-1.2	107	107
ALAS1	-0.17	0.19	-10000	0	-10000	0	0
TFRC	-0.63	0.42	-10000	0	-1	211	211
FOXF1	-0.002	0.12	-10000	0	-0.84	10	10
NF1	0.025	0.001	-10000	0	-10000	0	0
HNF1A (dimer)	-0.003	0.087	-10000	0	-0.79	5	5
CPT1A	-0.45	0.48	-10000	0	-1.2	109	109
HMGCS1	-0.45	0.48	-10000	0	-1.2	110	110
NR3C1	0.003	0.065	-10000	0	-0.96	1	1
CPT1B	-0.47	0.5	-10000	0	-1.2	106	106
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.017	0.005	-10000	0	-10000	0	0
GCK	-0.46	0.49	-10000	0	-1.2	117	117
CREB1	-0.028	0.065	-10000	0	-10000	0	0
IGFBP1	-0.32	0.42	-10000	0	-1	115	115
PDX1	-0.19	0.22	-10000	0	-1	6	6
UCP2	-0.45	0.48	-10000	0	-1.2	101	101
ALDOB	-0.94	0.62	-10000	0	-1.3	348	348
AFP	-0.71	0.5	-10000	0	-1	296	296
BDH1	-0.6	0.57	-10000	0	-1.3	174	174
HADH	-0.44	0.49	-10000	0	-1.2	99	99
F2	-0.66	0.62	-10000	0	-1.4	177	177
HNF1A	-0.003	0.087	-10000	0	-0.79	5	5
G6PC	-0.81	0.66	-10000	0	-1.5	241	241
SLC2A2	-0.32	0.48	-10000	0	-1.7	45	45
INS	0.01	0.055	-10000	0	-10000	0	0
FOXA1	-0.37	0.39	-10000	0	-1	118	118
FOXA3	-0.61	0.37	-10000	0	-0.86	313	313
FOXA2	-0.52	0.57	-10000	0	-1.4	111	111
ABCC8	-0.45	0.49	-10000	0	-1.2	101	101
ALB	-1.2	0.49	-10000	0	-1.4	438	438

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.054	-10000	0	-0.49	6	6
fibroblast growth factor receptor signaling pathway	-0.006	0.053	-10000	0	-0.49	6	6
LAMA1	-0.007	0.13	-10000	0	-0.76	15	15
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.56	108	108
SMAD2	0.045	0.021	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.022	-10000	0	-0.49	1	1
GPC1/Laminin alpha1	-0.018	0.099	-10000	0	-0.57	16	16
TDGF1	-0.56	0.32	-10000	0	-0.75	382	382
CRIPTO/GPC1	-0.42	0.24	-10000	0	-0.56	382	382
APP/GPC1	-0.002	0.035	-10000	0	-0.56	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.35	0.22	-10000	0	-0.48	382	382
FLT1	0.007	0.087	-10000	0	-0.86	5	5
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.021	-10000	0	-0.48	1	1
SERPINC1	-0.055	0.22	-10000	0	-0.76	45	45
FYN	-0.35	0.22	-10000	0	-0.48	382	382
FGR	-0.36	0.22	-10000	0	-0.48	382	382
positive regulation of MAPKKK cascade	-0.36	0.24	-10000	0	-0.49	382	382
SLIT2	-0.15	0.31	-10000	0	-0.75	107	107
GPC1/NRG	-0.019	0.1	-10000	0	-0.56	17	17
NRG1	-0.008	0.13	-10000	0	-0.75	16	16
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.26	0.3	-10000	0	-0.58	226	226
LYN	-0.35	0.22	-10000	0	-0.48	382	382
mol:Spermine	0.014	0.026	-10000	0	-0.57	1	1
cell growth	-0.006	0.053	-10000	0	-0.49	6	6
BMP signaling pathway	-0.014	0.034	0.75	1	-10000	0	1
SRC	-0.35	0.22	-10000	0	-0.48	382	382
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.064	0.24	-10000	0	-0.86	43	43
GPC1	0.014	0.034	-10000	0	-0.75	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.37	0.44	-10000	0	-0.86	225	225
BLK	-0.39	0.26	-10000	0	-0.52	387	387
HCK	-0.38	0.24	-10000	0	-0.5	392	392
FGF2	0.008	0.078	-10000	0	-0.77	5	5
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.007	0.087	-10000	0	-0.86	5	5
TGFBR2	0.016	0	-10000	0	-10000	0	0
cell death	-0.002	0.035	-10000	0	-0.56	2	2
ATIII/GPC1	-0.052	0.17	-10000	0	-0.58	46	46
PLA2G2A/GPC1	-0.058	0.19	-10000	0	-0.66	44	44
LCK	-0.38	0.24	-10000	0	-0.5	390	390
neuron differentiation	-0.019	0.1	-10000	0	-0.56	17	17
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.034	-10000	0	-0.75	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	-0.2	0.68	-10000	0	-1.2	122	122
PLK1	-0.11	0.41	-10000	0	-0.79	128	128
BIRC5	-0.14	0.43	-10000	0	-0.78	151	151
HSPA1B	-0.2	0.68	-10000	0	-1.2	122	122
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.2	0.69	-10000	0	-1.2	123	123
FOXM1	-0.38	1	-10000	0	-1.8	133	133
XRCC1	-0.2	0.68	-10000	0	-1.2	119	119
FOXM1B/p19	-0.5	0.49	0.51	1	-1.2	133	134
Cyclin D1/CDK4	-0.19	0.61	-10000	0	-1.1	109	109
CDC2	-0.22	0.72	-10000	0	-1.3	133	133
TGFA	-0.17	0.6	-10000	0	-1.1	112	112
SKP2	-0.2	0.68	-10000	0	-1.2	122	122
CCNE1	0.003	0.1	-10000	0	-0.87	7	7
CKS1B	-0.2	0.68	-10000	0	-1.2	121	121
RB1	-0.19	0.26	-10000	0	-0.69	90	90
FOXM1C/SP1	-0.29	0.78	-10000	0	-1.5	130	130
AURKB	-0.26	0.46	-10000	0	-0.76	211	211
CENPF	-0.22	0.72	-10000	0	-1.3	120	120
CDK4	0.02	0.022	-10000	0	-10000	0	0
MYC	-0.16	0.6	-10000	0	-1	120	120
CHEK2	0.038	0.063	-10000	0	-0.91	1	1
ONECUT1	-0.2	0.65	-10000	0	-1.2	119	119
CDKN2A	-0.82	0.17	-10000	0	-0.85	487	487
LAMA4	-0.29	0.7	-10000	0	-1.2	135	135
FOXM1B/HNF6	-0.29	0.79	-10000	0	-1.5	122	122
FOS	-0.21	0.69	-10000	0	-1.2	125	125
SP1	0.017	0.005	-10000	0	-10000	0	0
CDC25B	-0.2	0.68	-10000	0	-1.2	119	119
response to radiation	0.013	0.05	-10000	0	-10000	0	0
CENPB	-0.2	0.68	-10000	0	-1.2	122	122
CENPA	-0.3	0.78	-10000	0	-1.4	144	144
NEK2	-0.25	0.75	-10000	0	-1.4	132	132
HIST1H2BA	-0.21	0.68	-10000	0	-1.2	122	122
CCNA2	-0.16	0.36	-10000	0	-0.88	100	100
EP300	0.014	0.034	-10000	0	-0.75	1	1
CCNB1/CDK1	-0.28	0.81	-10000	0	-1.5	127	127
CCNB2	-0.25	0.76	-10000	0	-1.4	133	133
CCNB1	-0.22	0.72	-10000	0	-1.3	123	123
ETV5	-0.2	0.68	-10000	0	-1.2	118	118
ESR1	-0.2	0.68	-10000	0	-1.2	120	120
CCND1	-0.19	0.63	-10000	0	-1.1	116	116
GSK3A	0.036	0.041	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.083	0.28	-10000	0	-0.64	101	101
CDK2	0.015	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.43	0.59	-10000	0	-1.3	137	137
GAS1	-0.24	0.71	-10000	0	-1.2	135	135
MMP2	-0.2	0.68	-10000	0	-1.2	122	122
RB1/FOXM1C	-0.22	0.67	-10000	0	-1.2	120	120
CREBBP	0.016	0	-10000	0	-10000	0	0

×

IL12-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.17	0.26	-10000	0	-0.65	69	69
TBX21	-0.54	0.68	-10000	0	-1.3	198	198
B2M	0.011	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.022	-10000	0	-10000	0	0
IL12RB1	-0.27	0.43	-10000	0	-0.9	156	156
GADD45B	-0.29	0.43	-10000	0	-0.83	135	135
IL12RB2	-0.11	0.31	-10000	0	-0.87	73	73
GADD45G	-0.31	0.43	-10000	0	-0.84	143	143
natural killer cell activation	-0.01	0.03	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.002	0.1	-10000	0	-0.87	7	7
IL2RA	-0.16	0.35	-10000	0	-0.86	102	102
IFNG	-0.38	0.44	-10000	0	-0.86	230	230
STAT3 (dimer)	-0.37	0.47	-10000	0	-0.88	195	195
HLA-DRB5	-0.039	0.21	-10000	0	-0.86	32	32
FASLG	-0.6	0.7	-10000	0	-1.3	221	221
NF kappa B2 p52/RelB	-0.52	0.54	-10000	0	-1.1	202	202
CD4	0.002	0.11	-10000	0	-0.86	8	8
SOCS1	0.005	0.095	-10000	0	-0.86	6	6
EntrezGene:6955	-0.002	0.009	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	228	228
CD3E	-0.34	0.43	-10000	0	-0.87	204	204
CD3G	-0.33	0.43	-10000	0	-0.87	199	199
IL12Rbeta2/JAK2	-0.085	0.25	-10000	0	-0.68	73	73
CCL3	-0.48	0.63	-10000	0	-1.2	185	185
CCL4	-0.5	0.66	-10000	0	-1.3	181	181
HLA-A	0.009	0.04	-10000	0	-0.86	1	1
IL18/IL18R	-0.12	0.3	-10000	0	-0.6	141	141
NOS2	-0.36	0.5	-10000	0	-0.96	159	159
IL12/IL12R/TYK2/JAK2/SPHK2	-0.16	0.26	-10000	0	-0.65	66	66
IL1R1	-0.44	0.59	-10000	0	-1.2	164	164
IL4	0.013	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.022	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.7	0.82	-10000	0	-1.5	248	248
RAB7A	-0.23	0.37	-10000	0	-0.79	49	49
lysosomal transport	-0.22	0.36	-10000	0	-0.74	50	50
FOS	-0.38	0.5	-10000	0	-0.95	195	195
STAT4 (dimer)	-0.4	0.53	-10000	0	-0.99	191	191
STAT5A (dimer)	-0.65	0.61	-10000	0	-1.3	230	230
GZMA	-0.56	0.7	-10000	0	-1.3	209	209
GZMB	-0.53	0.67	-10000	0	-1.3	193	193
HLX	-0.085	0.28	-10000	0	-0.86	58	58
LCK	-0.52	0.69	-10000	0	-1.3	202	202
TCR/CD3/MHC II/CD4	-0.37	0.47	-10000	0	-0.86	222	222
IL2/IL2R	-0.42	0.42	-10000	0	-0.71	300	300
MAPK14	-0.3	0.44	-10000	0	-0.83	153	153
CCR5	-0.45	0.59	-10000	0	-1.1	188	188
IL1B	0.002	0.097	-10000	0	-0.86	6	6
STAT6	-0.082	0.15	-10000	0	-10000	0	0
STAT4	-0.036	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.014	0.039	-10000	0	-0.86	1	1
NFKB1	0.014	0.034	-10000	0	-0.75	1	1
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.094	0.29	-10000	0	-0.89	60	60
CD8A	-0.39	0.44	-10000	0	-0.87	230	230
CD8B	-0.3	0.42	-10000	0	-0.87	181	181
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.16	0.26	0.64	69	-10000	0	69
IL2RB	-0.45	0.44	-10000	0	-0.86	267	267
proteasomal ubiquitin-dependent protein catabolic process	-0.36	0.47	-10000	0	-0.88	186	186
IL2RG	-0.043	0.22	-10000	0	-0.86	34	34
IL12	-0.071	0.24	-10000	0	-0.71	61	61
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.27	0.41	-10000	0	-0.87	165	165
IL2	-0.008	0.12	-10000	0	-0.86	10	10
SPHK2	0.013	0.048	-10000	0	-0.75	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.047	-10000	0	-0.91	1	1
IL12/IL12R/TYK2/JAK2	-0.58	0.78	-10000	0	-1.4	211	211
MAP2K3	-0.3	0.44	-10000	0	-0.83	157	157
RIPK2	0.014	0.039	-10000	0	-0.86	1	1
MAP2K6	-0.3	0.44	-10000	0	-0.83	157	157
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.078	-10000	0	-0.86	4	4
IL18RAP	-0.21	0.39	-10000	0	-0.87	129	129
IL12Rbeta1/TYK2	-0.21	0.34	-10000	0	-0.72	156	156
EOMES	-0.3	0.37	-10000	0	-0.74	209	209
STAT1 (dimer)	-0.44	0.51	-10000	0	-0.97	219	219
T cell proliferation	-0.26	0.37	-10000	0	-0.68	162	162
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.81	8	8
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.37	0.33	-10000	0	-0.76	173	173
ATF2	-0.27	0.41	-10000	0	-0.79	125	125

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.37	-9999	-0.75	196	196
PDGF/PDGFRA/CRKL	-0.21	0.26	-9999	-0.55	196	196
positive regulation of JUN kinase activity	-0.16	0.2	-9999	-0.52	1	1
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.22	0.27	-9999	-0.56	199	199
AP1	-0.16	0.25	-9999	-1.2	13	13
mol:IP3	-0.19	0.29	-9999	-0.56	196	196
PLCG1	-0.2	0.29	-9999	-0.56	196	196
PDGF/PDGFRA/alphaV Integrin	-0.21	0.26	-9999	-0.55	196	196
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.29	-9999	-0.56	196	196
CAV3	-0.001	0.067	-9999	-0.86	3	3
CAV1	-0.047	0.23	-9999	-0.86	36	36
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/Shf	-0.21	0.27	-9999	-0.55	197	197
FOS	-0.12	0.27	-9999	-1.2	13	13
JUN	-0.013	0.017	-9999	-10000	0	0
oligodendrocyte development	-0.21	0.26	-9999	-0.54	196	196
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
mol:DAG	-0.19	0.29	-9999	-0.56	196	196
PDGF/PDGFRA	-0.28	0.37	-9999	-0.74	196	196
actin cytoskeleton reorganization	-0.21	0.26	-9999	-0.54	196	196
SRF	0.034	0.009	-9999	-10000	0	0
SHC1	0.014	0.039	-9999	-0.86	1	1
PI3K	-0.18	0.22	-9999	-0.46	197	197
PDGF/PDGFRA/Crk/C3G	-0.18	0.22	-9999	-0.46	196	196
JAK1	-0.19	0.28	-9999	-0.54	196	196
ELK1/SRF	-0.15	0.19	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.034	-9999	-0.75	1	1
CSNK2A1	0.018	0.022	-9999	-10000	0	0
GO:0007205	-0.2	0.3	-9999	-0.57	196	196
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/SHB	-0.21	0.26	-9999	-0.55	196	196
PDGF/PDGFRA/Caveolin-1	-0.26	0.3	-9999	-0.58	225	225
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.26	-9999	-0.49	196	196
PIK3CA	0.014	0.034	-9999	-0.75	1	1
PDGF/PDGFRA/Crk	-0.21	0.26	-9999	-0.55	196	196
JAK-STAT cascade	-0.19	0.28	-9999	-0.54	196	196
cell proliferation	-0.21	0.26	-9999	-0.54	197	197

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.14	0.28	-9999	-0.67	102	102
alphaM/beta2 Integrin/GPIbA	-0.13	0.28	-9999	-0.67	98	98
alphaM/beta2 Integrin/proMMP-9	-0.4	0.42	-9999	-0.74	270	270
PLAUR	-0.029	0.19	-9999	-0.86	26	26
HMGB1	0.015	0.013	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.13	0.28	-9999	-0.67	97	97
AGER	-0.14	0.33	-9999	-0.86	88	88
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.042	0.22	-9999	-0.86	33	33
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.22	0.33	-9999	-0.66	163	163
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.41	0.44	-9999	-0.86	243	243
CYR61	0.007	0.083	-9999	-0.75	6	6
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.25	0.2	-9999	-0.56	113	113
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.019	0.16	-9999	-0.75	23	23
MYH2	-0.35	0.26	-9999	-0.64	182	182
MST1R	0.005	0.093	-9999	-0.78	7	7
leukocyte activation during inflammatory response	-0.28	0.35	-9999	-0.63	216	216
APOB	-0.27	0.41	-9999	-0.85	167	167
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.006	0.093	-9999	-0.84	6	6
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.034	-9999	-0.75	1	1
alphaM/beta2 Integrin/CTGF	-0.14	0.29	-9999	-0.67	102	102
alphaM/beta2 Integrin	-0.3	0.25	-9999	-0.54	218	218
JAM3 homodimer	0.016	0	-9999	-10000	0	0
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	-0.003	0.13	-9999	-0.86	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.3	0.24	-9999	-0.53	218	218
cell adhesion	-0.13	0.28	-9999	-0.67	98	98
NFKB1	-0.17	0.37	-9999	-0.95	60	60
THY1	0.014	0.034	-9999	-0.75	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.2	0.28	-9999	-0.59	168	168
alphaM/beta2 Integrin/LRP/tPA	-0.13	0.27	-9999	-0.62	99	99
IL6	-0.2	0.41	-9999	-0.92	95	95
ITGB2	-0.15	0.34	-9999	-0.86	95	95
elevation of cytosolic calcium ion concentration	-0.15	0.29	-9999	-0.63	117	117
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.26	-9999	-0.62	97	97
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.13	0.28	-9999	-0.71	62	62
alphaM/beta2 Integrin/uPA/Plg	-0.35	0.34	-9999	-0.78	133	133
RhoA/GTP	-0.37	0.27	-9999	-0.68	182	182
positive regulation of phagocytosis	-0.25	0.27	-9999	-0.7	107	107
Ron/MSP	-0.018	0.11	-9999	-0.62	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.15	0.3	-9999	-0.64	117	117
alphaM/beta2 Integrin/uPAR	-0.16	0.32	-9999	-0.7	113	113
PLAU	0.002	0.1	-9999	-0.75	9	9
PLAT	-0.004	0.12	-9999	-0.75	13	13
actin filament polymerization	-0.33	0.24	-9999	-0.61	182	182
MST1	0.002	0.11	-9999	-0.85	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.28	0.36	-9999	-0.64	216	216
TNF	-0.15	0.34	-9999	-0.84	64	64
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.14	0.28	-9999	-0.66	106	106
fibrinolysis	-0.35	0.33	-9999	-0.76	133	133
HCK	-0.033	0.2	-9999	-0.86	28	28
dendritic cell antigen processing and presentation	-0.3	0.24	-9999	-0.53	218	218
VTN	-0.1	0.28	-9999	-0.76	78	78
alphaM/beta2 Integrin/CYR61	-0.14	0.28	-9999	-0.66	103	103
LPA	0.002	0.067	-9999	-0.86	3	3
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.37	0.4	-9999	-0.69	272	272
FN1	-0.05	0.23	-9999	-0.86	38	38
alphaM/beta2 Integrin/Thy1	-0.13	0.28	-9999	-0.67	98	98
MPO	-0.013	0.15	-9999	-0.86	16	16
KNG1	-0.56	0.32	-9999	-0.75	379	379
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.33	0.26	-9999	-0.64	171	171
ELA2	0	0	-9999	-10000	0	0
PLG	-0.39	0.38	-9999	-0.75	265	265
CTGF	0.005	0.089	-9999	-0.75	7	7
alphaM/beta2 Integrin/Hck	-0.16	0.35	-9999	-0.79	101	101
ITGAM	-0.02	0.17	-9999	-0.86	20	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.17	0.34	-9999	-0.74	106	106
HP	-0.2	0.38	-9999	-0.86	127	127
leukocyte adhesion	-0.18	0.27	-9999	-0.81	51	51
SELP	-0.019	0.16	-9999	-0.75	23	23

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.41	0.54	-9999	-0.91	228	228
MAP4K1	-0.33	0.43	-9999	-0.86	201	201
MAP3K8	0.012	0.055	-9999	-0.86	2	2
PRKCB	0.007	0.082	-9999	-0.82	5	5
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	-0.15	0.3	-9999	-0.62	120	120
JUN	0.003	0.075	-9999	-0.53	4	4
MAP3K7	-0.15	0.3	-9999	-0.62	120	120
GRAP2	-0.043	0.22	-9999	-0.86	34	34
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.13	0.29	-9999	-0.59	120	120
LAT	-0.23	0.4	-9999	-0.86	144	144
LCP2	-0.04	0.21	-9999	-0.86	32	32
MAPK8	-0.009	0.079	-9999	-0.57	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.2	0.29	-9999	-0.66	120	120
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.39	0.51	-9999	-1.2	120	120

×

IL4-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.48	-10000	0	-1.2	105	105
STAT6 (cleaved dimer)	-0.58	0.5	-10000	0	-1.2	156	156
IGHG1	-0.17	0.19	-10000	0	-0.68	11	11
IGHG3	-0.47	0.46	-10000	0	-1.1	117	117
AKT1	-0.28	0.34	-10000	0	-0.84	81	81
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.25	0.32	-10000	0	-0.81	85	85
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.81	61	61
THY1	-0.48	0.48	-10000	0	-1.2	89	89
MYB	-0.22	0.39	-10000	0	-0.86	139	139
HMGA1	0.014	0.039	-10000	0	-0.86	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.42	-10000	0	-1	114	114
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.8	63	63
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.009	0.078	-10000	0	-0.86	4	4
SOCS5	0.026	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.48	-10000	0	-1.2	141	141
SOCS1	-0.33	0.34	-10000	0	-0.83	61	61
SOCS3	-0.3	0.34	-10000	0	-0.95	57	57
FCER2	-0.41	0.44	-10000	0	-1.2	72	72
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.5	0.5	-10000	0	-1.3	96	96
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.28	-10000	0	-0.79	52	52
T cell proliferation	-0.5	0.52	-10000	0	-1.2	118	118
IL4R/JAK1	-0.48	0.48	-10000	0	-1.2	105	105
EGR2	-0.49	0.5	-10000	0	-1.3	88	88
JAK2	0.007	0.024	-10000	0	-10000	0	0
JAK3	-0.16	0.36	-10000	0	-0.86	104	104
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
JAK1	0.007	0.016	-10000	0	-10000	0	0
COL1A2	-0.21	0.3	-10000	0	-0.89	66	66
CCL26	-0.49	0.49	-10000	0	-1.2	92	92
IL4R	-0.51	0.51	-10000	0	-1.3	105	105
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.55	0.56	-10000	0	-1.3	125	125
IL13RA1	0.007	0.024	-10000	0	-10000	0	0
IRF4	-0.27	0.42	-10000	0	-0.96	123	123
ARG1	-0.17	0.26	-10000	0	-0.78	42	42
CBL	-0.36	0.4	-10000	0	-0.96	106	106
GTF3A	0.011	0.029	-10000	0	-10000	0	0
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
IL13RA1/JAK2	-0.006	0.044	-10000	0	-10000	0	0
IRF4/BCL6	-0.27	0.38	-10000	0	-0.9	119	119
CD40LG	-0.076	0.29	-10000	0	-0.91	53	53
MAPK14	-0.35	0.4	-10000	0	-0.98	96	96
mitosis	-0.26	0.32	-10000	0	-0.79	81	81
STAT6	-0.55	0.56	-10000	0	-1.4	112	112
SPI1	-0.098	0.3	-10000	0	-0.86	68	68
RPS6KB1	-0.24	0.31	-10000	0	-0.8	61	61
STAT6 (dimer)	-0.55	0.56	-10000	0	-1.4	112	112
STAT6 (dimer)/PARP14	-0.51	0.52	-10000	0	-1.3	114	114
mast cell activation	0.012	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.36	-10000	0	-0.91	93	93
FRAP1	-0.28	0.34	-10000	0	-0.84	81	81
LTA	-0.6	0.56	-10000	0	-1.3	144	144
FES	0.013	0.048	-10000	0	-0.75	2	2
T-helper 1 cell differentiation	0.54	0.54	1.3	112	-10000	0	112
CCL11	-0.69	0.61	-10000	0	-1.3	209	209
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.29	0.34	-10000	0	-0.88	85	85
IL2RG	-0.038	0.22	-10000	0	-0.85	34	34
IL10	-0.5	0.51	-10000	0	-1.3	99	99
IRS1	0.011	0.059	-10000	0	-0.75	3	3
IRS2	0.002	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.13	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.2	91	91
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.38	-10000	0	-0.91	84	84
COL1A1	-0.41	0.43	-10000	0	-0.92	192	192
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.49	-10000	0	-1.3	82	82
IL2R gamma/JAK3	-0.16	0.37	-10000	0	-0.83	108	108
TFF3	-0.5	0.51	-10000	0	-1.2	107	107
ALOX15	-0.48	0.48	-10000	0	-1.2	88	88
MYBL1	-0.047	0.23	-10000	0	-0.86	36	36
T-helper 2 cell differentiation	-0.43	0.42	-10000	0	-0.99	115	115
SHC1	0.014	0.039	-10000	0	-0.86	1	1
CEBPB	-0.001	0.14	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.3	-10000	0	-0.78	67	67
mol:PI-3-4-5-P3	-0.28	0.34	-10000	0	-0.84	81	81
PI3K	-0.3	0.36	-10000	0	-0.92	81	81
DOK2	-0.038	0.21	-10000	0	-0.86	31	31
ETS1	0.028	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.27	-10000	0	-0.77	53	53
ITGB3	-0.48	0.49	-10000	0	-1.2	92	92
PIGR	-0.84	0.71	-10000	0	-1.5	260	260
IGHE	0.027	0.091	0.29	7	-0.37	4	11
MAPKKK cascade	-0.21	0.27	-10000	0	-0.75	53	53
BCL6	0.013	0.005	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	96	96
RETNLB	-0.49	0.48	-10000	0	-1.2	91	91
SELP	-0.51	0.53	-10000	0	-1.3	97	97
AICDA	-0.62	0.55	-10000	0	-1.2	174	174

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.014	0.039	-9999	-0.86	1	1
EGFR	0	0.11	-9999	-0.85	9	9
EGF/EGFR	-0.38	0.16	-9999	-0.86	26	26
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.36	0.14	-9999	-0.9	9	9
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.012	0.055	-9999	-0.86	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.75	455	455
EGF/EGFR dimer/SHC	-0.44	0.16	-9999	-0.49	456	456
mol:GDP	-0.36	0.14	-9999	-0.88	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.014	0.16	-9999	-0.86	17	17
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.33	0.13	-9999	-0.82	10	10
SHC1	0.014	0.039	-9999	-0.86	1	1
HRAS/GDP	-0.34	0.13	-9999	-0.82	10	10
FRAP1	-0.35	0.13	-9999	-0.85	9	9
EGF/EGFR dimer	-0.51	0.18	-9999	-0.57	456	456
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.025	0.12	-9999	-0.66	19	19

×

Aurora C signaling

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
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.25	0.27	-9999	-0.53	241	241
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.065	0.068	-9999	-10000	0	0
AURKB	-0.4	0.44	-9999	-0.86	240	240
AURKC	0.012	0.055	-9999	-0.86	2	2

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.087	-9999	-0.86	5	5
CCL5	-0.36	0.43	-9999	-0.86	215	215
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.22	0.23	-9999	-0.59	89	89
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.22	-9999	-0.56	89	89
Syndecan-1/Syntenin	-0.2	0.22	-9999	-0.56	89	89
MAPK3	-0.16	0.2	-9999	-0.54	51	51
HGF/MET	-0.034	0.15	-9999	-0.66	26	26
TGFB1/TGF beta receptor Type II	0.007	0.087	-9999	-0.86	5	5
BSG	0.014	0.039	-9999	-0.86	1	1
keratinocyte migration	-0.2	0.21	-9999	-0.55	89	89
Syndecan-1/RANTES	-0.42	0.33	-9999	-0.68	268	268
Syndecan-1/CD147	-0.2	0.19	-9999	-0.53	90	90
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	89	89
LAMA5	0.014	0.034	-9999	-0.75	1	1
positive regulation of cell-cell adhesion	-0.21	0.18	-9999	-0.52	89	89
MMP7	-0.12	0.3	-9999	-0.76	90	90
HGF	-0.021	0.17	-9999	-0.8	23	23
Syndecan-1/CASK	-0.21	0.22	-9999	-0.57	89	89
Syndecan-1/HGF/MET	-0.23	0.22	-9999	-0.58	105	105
regulation of cell adhesion	-0.15	0.2	-9999	-0.67	15	15
HPSE	0.013	0.048	-9999	-0.75	2	2
positive regulation of cell migration	-0.22	0.23	-9999	-0.59	89	89
SDC1	-0.22	0.23	-9999	-0.6	89	89
Syndecan-1/Collagen	-0.22	0.23	-9999	-0.59	89	89
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.087	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.41	0.44	-9999	-0.86	243	243
MAPK1	-0.16	0.2	-9999	-0.54	51	51
homophilic cell adhesion	-0.22	0.22	-9999	-0.58	89	89
MMP1	-0.15	0.34	-9999	-0.83	99	99

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.048	0.23	-9999	-0.86	37	37
GPC2	-0.087	0.28	-9999	-0.86	59	59
GPC2/Midkine	-0.12	0.28	-9999	-0.73	85	85
neuron projection morphogenesis	-0.12	0.28	-9999	-0.73	85	85

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.027	0.081	-10000	0	-0.73	6	6
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.011	0.065	-10000	0	-0.82	3	3
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.23	0.14	-10000	0	-0.64	3	3
EPO	-0.4	0.41	-10000	0	-0.9	140	140
FIH (dimer)	0.014	0.02	-10000	0	-10000	0	0
APEX1	0.013	0.014	-10000	0	-10000	0	0
SERPINE1	-0.34	0.41	-10000	0	-0.92	112	112
FLT1	-0.018	0.078	-10000	0	-0.76	5	5
ADORA2A	-0.3	0.34	-10000	0	-0.82	75	75
germ cell development	-0.39	0.44	-10000	0	-0.88	193	193
SLC11A2	-0.28	0.34	-10000	0	-0.81	75	75
BHLHE40	-0.28	0.34	-10000	0	-0.81	75	75
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.52	205	205
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.023	0.058	-10000	0	-1.2	1	1
KDR	-0.015	0.067	-10000	0	-1.4	1	1
PGK1	-0.28	0.34	-10000	0	-0.81	75	75
SIRT1	0.014	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.34	0.42	-10000	0	-0.86	147	147
EPAS1	-0.27	0.19	-10000	0	-0.44	208	208
SP1	0.026	0.005	-10000	0	-10000	0	0
ABCG2	-0.28	0.34	-10000	0	-0.82	76	76
EFNA1	-0.28	0.34	-10000	0	-0.81	76	76
FXN	-0.3	0.34	-10000	0	-0.82	75	75
POU5F1	-0.42	0.47	-10000	0	-0.94	193	193
neuron apoptosis	0.33	0.4	0.82	147	-10000	0	147
EP300	0.014	0.034	-10000	0	-0.75	1	1
EGLN3	-0.76	0.3	-10000	0	-0.87	444	444
EGLN2	0.012	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.003	0.042	-10000	0	-0.54	3	3
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.31	0.37	-10000	0	-0.9	80	80
TWIST1	-0.3	0.34	-10000	0	-0.83	78	78
ELK1	0.026	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.56	76	76
VEGFA	-0.46	0.49	-10000	0	-0.94	231	231
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.13	0.26	-10000	0	-0.58	101	101
ACTA1	-0.19	0.35	-10000	0	-0.67	162	162
NUMA1	-0.13	0.26	-10000	0	-0.58	101	101
SPTAN1	-0.18	0.35	-10000	0	-0.66	161	161
LIMK1	-0.18	0.35	-10000	0	-0.66	162	162
BIRC3	-0.12	0.32	-10000	0	-0.86	78	78
BIRC2	0.012	0.007	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.28	0.46	-10000	0	-0.86	178	178
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.015	0.003	-10000	0	-10000	0	0
PTK2	-0.13	0.26	-10000	0	-0.49	161	161
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.34	-10000	0	-0.65	161	161
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.18	0.35	-10000	0	-0.66	161	161
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.29	0.28	-10000	0	-0.54	274	274
BID	-0.088	0.17	-10000	0	-0.37	99	99
MAP3K1	-0.043	0.11	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.18	0.35	-10000	0	-0.66	161	161
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.012	0.094	-10000	0	-0.21	35	35
neuron apoptosis	0.011	0.045	-10000	0	-0.62	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.17	0.34	-10000	0	-0.77	99	99
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.048	0.15	-10000	0	-0.52	3	3
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.17	0.34	-10000	0	-0.77	99	99
CASP7	0.05	0.13	0.34	78	-10000	0	78
KRT18	-0.001	0.046	-10000	0	-0.3	2	2
apoptosis	-0.17	0.32	-10000	0	-0.69	106	106
DFFA	-0.18	0.35	-10000	0	-0.8	99	99
DFFB	-0.18	0.35	-10000	0	-0.66	161	161
PARP1	-0.012	0.095	0.21	35	-10000	0	35
actin filament polymerization	0.16	0.32	0.72	100	-10000	0	100
TNF	0.003	0.1	-10000	0	-0.8	8	8
CYCS	-0.067	0.13	-10000	0	-0.28	99	99
SATB1	-0.035	0.15	-10000	0	-0.48	3	3
SLK	-0.18	0.35	-10000	0	-0.66	161	161
p15 BID/BAX	-0.072	0.15	-10000	0	-10000	0	0
CASP2	0.031	0.089	-10000	0	-10000	0	0
JNK cascade	0.042	0.11	-10000	0	-10000	0	0
CASP3	-0.2	0.37	-10000	0	-0.71	161	161
LMNB2	0.012	0.085	-10000	0	-0.39	4	4
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.08	0.19	-10000	0	-0.52	78	78
negative regulation of DNA binding	-0.29	0.28	-10000	0	-0.54	274	274
stress fiber formation	-0.18	0.34	-10000	0	-0.65	161	161
GZMB	-0.32	0.5	-10000	0	-0.97	178	178
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.009	0.089	-10000	0	-0.36	7	7
APP	0.011	0.045	-10000	0	-0.62	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	-0.17	0.31	-10000	0	-0.66	107	107
LMNA	0.011	0.085	-10000	0	-0.41	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.03	0.073	-10000	0	-0.41	7	7
LRDD	0.004	0.1	-10000	0	-0.84	7	7
SREBF1	-0.18	0.35	-10000	0	-0.66	162	162
APAF-1/Caspase 9	-0.009	0.063	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.12	0.26	-10000	0	-0.57	101	101
CFL2	-0.16	0.33	-10000	0	-0.75	100	100
GAS2	-0.2	0.36	-10000	0	-0.66	165	165
positive regulation of apoptosis	0.016	0.085	-10000	0	-0.4	3	3
PRF1	-0.2	0.38	-10000	0	-0.86	126	126

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.008	0.073	-9999	-0.68	5	5
VEGFR1 homodimer/NRP1	-0.009	0.074	-9999	-0.62	7	7
mol:DAG	-0.26	0.29	-9999	-0.52	281	281
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	226	226
CaM/Ca2+	-0.27	0.25	-9999	-0.92	7	7
HIF1A	0.019	0.058	-9999	-0.73	2	2
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.23	0.21	-9999	-0.94	6	6
PLCG1	-0.27	0.29	-9999	-0.52	281	281
NOS3	-0.18	0.24	-9999	-0.85	6	6
CBL	0.014	0.034	-9999	-0.75	1	1
mol:NO	-0.17	0.24	-9999	-0.8	6	6
FLT1	0.031	0.088	-9999	-0.71	7	7
PGF	-0.47	0.44	-9999	-0.86	280	280
VEGFR1 homodimer/NRP2/VEGFR121	-0.24	0.27	-9999	-0.53	231	231
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
eNOS/Hsp90	-0.16	0.23	-9999	-0.76	6	6
endothelial cell proliferation	-0.2	0.26	-9999	-0.86	8	8
mol:Ca2+	-0.26	0.29	-9999	-0.52	281	281
MAPK3	-0.21	0.26	-9999	-0.88	6	6
MAPK1	-0.21	0.26	-9999	-0.88	6	6
PIK3R1	0.014	0.034	-9999	-0.75	1	1
PLGF homodimer	-0.47	0.44	-9999	-0.86	280	280
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.047	0.23	-9999	-0.86	36	36
VEGFA homodimer	-0.37	0.44	-9999	-0.86	225	225
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	226	226
platelet activating factor biosynthetic process	-0.2	0.25	-9999	-0.85	6	6
PI3K	-0.27	0.25	-9999	-0.99	7	7
PRKCA	-0.24	0.27	-9999	-0.89	7	7
PRKCB	-0.24	0.28	-9999	-0.9	9	9
VEGFR1 homodimer/PLGF homodimer	-0.32	0.29	-9999	-0.58	281	281
VEGFA	-0.37	0.44	-9999	-0.86	225	225
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.52	281	281
RASA1	0.045	0.08	-9999	-0.65	6	6
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFR1 homodimer	0.031	0.088	-9999	-0.7	7	7
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.014	0.034	-9999	-0.75	1	1
eNOS/Caveolin-1	-0.19	0.26	-9999	-0.8	31	31
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.27	0.25	-9999	-0.96	7	7
mol:L-citrulline	-0.17	0.24	-9999	-0.8	6	6
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.22	0.25	-9999	-0.94	6	6
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.24	0.27	-9999	-0.53	227	227
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.93	7	7
PDPK1	-0.22	0.27	-9999	-1	6	6
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-1	5	5
mol:NADP	-0.17	0.24	-9999	-0.8	6	6
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.22	0.25	-9999	-0.92	6	6
VEGFR1 homodimer/NRP2	-0.016	0.098	-9999	-0.61	12	12

×

IL23-mediated signaling events

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
CCL2	-0.26	0.48	-10000	0	-1.1	63	63
IL23A	-0.24	0.47	-10000	0	-1.1	46	46
NF kappa B1 p50/RelA/I kappa B alpha	-0.33	0.39	-10000	0	-1	76	76
positive regulation of T cell mediated cytotoxicity	-0.29	0.52	-10000	0	-1.1	88	88
ITGA3	-0.24	0.47	-10000	0	-1	66	66
IL17F	-0.15	0.34	-10000	0	-0.75	29	29
IL12B	-0.088	0.29	-10000	0	-0.88	60	60
STAT1 (dimer)	-0.28	0.5	-10000	0	-1.1	79	79
CD4	-0.25	0.47	-10000	0	-1.1	59	59
IL23	-0.28	0.48	-10000	0	-1.1	63	63
IL23R	-0.014	0.15	-10000	0	-0.8	10	10
IL1B	-0.26	0.48	-10000	0	-1.1	60	60
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.25	0.47	-10000	0	-1.1	67	67
TYK2	0.015	0.024	-10000	0	-10000	0	0
STAT4	-0.036	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0.001	-10000	0	-10000	0	0
IL18RAP	-0.22	0.39	-10000	0	-0.88	129	129
IL12RB1	-0.26	0.42	-10000	0	-0.89	156	156
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
IL12Rbeta1/TYK2	-0.2	0.34	-10000	0	-0.7	156	156
IL23R/JAK2	-0.012	0.16	-10000	0	-0.75	10	10
positive regulation of chronic inflammatory response	-0.29	0.52	-10000	0	-1.1	88	88
natural killer cell activation	0.002	0.012	0.063	10	-10000	0	10
JAK2	0.021	0.034	-10000	0	-10000	0	0
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
NFKB1	0.01	0.034	-10000	0	-0.74	1	1
RELA	0.011	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.26	0.46	-10000	0	-1.1	63	63
ALOX12B	-0.31	0.5	-10000	0	-1.1	77	77
CXCL1	-0.29	0.52	-10000	0	-1.1	82	82
T cell proliferation	-0.29	0.52	-10000	0	-1.1	88	88
NFKBIA	0.011	0.009	-10000	0	-10000	0	0
IL17A	-0.1	0.29	-10000	0	-0.6	5	5
PI3K	-0.34	0.4	-10000	0	-1	87	87
IFNG	-0.052	0.069	0.13	4	-0.12	229	233
STAT3 (dimer)	-0.32	0.38	-10000	0	-1	76	76
IL18R1	-0.004	0.1	-10000	0	-0.81	8	8
IL23/IL23R/JAK2/TYK2/SOCS3	-0.19	0.38	-10000	0	-0.8	81	81
IL18/IL18R	-0.17	0.28	-10000	0	-0.61	141	141
macrophage activation	-0.017	0.018	-10000	0	-0.044	20	20
TNF	-0.26	0.49	-10000	0	-1.1	67	67
STAT3/STAT4	-0.36	0.43	-10000	0	-1.1	96	96
STAT4 (dimer)	-0.3	0.53	-10000	0	-1.2	89	89
IL18	-0.003	0.1	-10000	0	-0.86	7	7
IL19	-0.26	0.46	-10000	0	-1	67	67
STAT5A (dimer)	-0.28	0.5	-10000	0	-1.1	82	82
STAT1	0.014	0.039	-10000	0	-0.86	1	1
SOCS3	0.012	0.055	-10000	0	-0.86	2	2
CXCL9	-0.4	0.59	-10000	0	-1.1	154	154
MPO	-0.26	0.48	-10000	0	-1.1	67	67
positive regulation of humoral immune response	-0.29	0.52	-10000	0	-1.1	88	88
IL23/IL23R/JAK2/TYK2	-0.31	0.54	-10000	0	-1.2	87	87
IL6	-0.3	0.53	-10000	0	-1.1	89	89
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.017	0.12	-10000	0	-0.86	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.063	10	-10000	0	10
CD3E	-0.39	0.6	-10000	0	-1.1	159	159
keratinocyte proliferation	-0.29	0.52	-10000	0	-1.1	88	88
NOS2	-0.25	0.47	-10000	0	-1.1	67	67

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.006	0.13	-9999	-0.78	14	14
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.065	-9999	-0.82	3	3
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.048	-9999	-0.39	1	1
HIF1A	-0.098	0.04	-9999	-0.42	1	1
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.035	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	487	487
ARNT/IPAS	-0.016	0.097	-9999	-0.59	14	14
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.014	0.039	-9999	-0.86	1	1
HIF1A/ARNT	-0.08	0.048	-9999	-0.39	1	1
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.004	0.049	-9999	-0.55	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.048	-9999	-0.39	1	1
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	443	443
HIF1A/RACK1/Elongin B/Elongin C	-0.067	0.05	-9999	-0.59	3	3
VHL	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.048	-9999	-0.39	1	1
EGLN3	-0.75	0.29	-9999	-0.86	444	444
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.002	0.022	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.55	0.11	-9999	-0.57	487	487

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.6	0.31	-9999	-0.86	268	268
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.32	-9999	-0.84	81	81
SMAD9	-0.063	0.082	-9999	-0.58	9	9
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.18	0.17	-9999	-0.52	18	18
BMP7/USAG1	-0.7	0.34	-9999	-0.8	441	441
SMAD5/SKI	-0.17	0.16	-9999	-0.5	14	14
SMAD1	0.002	0.042	-9999	-10000	0	0
BMP2	0.009	0.07	-9999	-0.78	4	4
SMAD1/SMAD1/SMAD4	0	0.001	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.51	0.35	-9999	-0.75	346	346
BMPR1A-1B/BAMBI	-0.33	0.23	-9999	-0.48	349	349
AHSG	-0.011	0.13	-9999	-0.86	11	11
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.007	0.059	-9999	-0.5	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.11	-9999	-0.49	18	18
BMP2-4 (homodimer)	-0.008	0.067	-9999	-0.58	7	7
RGMB	0.012	0.055	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.79	5	5
RGMA	0.008	0.075	-9999	-0.75	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.17	0.13	-9999	-0.56	18	18
BMP2-4/USAG1	-0.32	0.24	-9999	-0.88	7	7
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	14	14
SOSTDC1	-0.48	0.36	-9999	-0.75	327	327
BMP7/BMPR2/BMPR1A-1B	-0.58	0.3	-9999	-0.86	249	249
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.095	-9999	-0.75	8	8
HFE2	-0.019	0.16	-9999	-0.86	18	18
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.018	0.1	-9999	-0.56	16	16
SMAD5/SMAD5/SMAD4	-0.17	0.16	-9999	-0.5	14	14
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.1	-9999	-0.5	14	14
BMP7 (homodimer)	-0.5	0.35	-9999	-0.75	340	340
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.023	0.12	-9999	-0.62	19	19
SMAD1/SKI	0.012	0.039	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.019	0.1	-9999	-0.54	18	18
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.17	0.33	-9999	-0.76	122	122
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.38	0.26	-9999	-0.56	346	346
CHRDL1	-0.38	0.38	-9999	-0.75	263	263
ENDOFIN/SMAD1	0.012	0.039	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.005	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	0.005	0.089	-9999	-0.75	7	7
SMURF2	0.014	0.034	-9999	-0.75	1	1
BMP2-4/CHRDL1	-0.25	0.25	-9999	-0.48	265	265
BMP2-4/GREM1	-0.12	0.22	-9999	-0.64	12	12
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.037	0.087	-9999	-0.54	9	9
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.5	0.36	-9999	-0.75	340	340
BMP6	0.004	0.095	-9999	-0.75	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.12	0.13	-9999	-0.46	18	18
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.011	0.042	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.21	0.18	-9999	-0.6	62	62
CHRD	-0.002	0.12	-9999	-0.78	11	11
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.17	0.13	-9999	-0.58	18	18
BMP4	0.011	0.059	-9999	-0.75	3	3
FST	-0.074	0.25	-9999	-0.77	58	58
BMP2-4/NOG	-0.096	0.21	-9999	-0.56	87	87
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.55	0.29	-9999	-0.81	249	249

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.25	0.26	-10000	0	-0.74	32	32
IHH	-0.099	0.23	-10000	0	-0.82	46	46
SHH Np/Cholesterol/GAS1	-0.038	0.13	-10000	0	-0.45	42	42
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.037	0.13	0.45	42	-10000	0	42
SMO/beta Arrestin2	-0.15	0.15	-10000	0	-0.6	33	33
SMO	-0.13	0.19	-10000	0	-0.64	33	33
AKT1	-0.042	0.093	-10000	0	-0.46	1	1
ARRB2	0.014	0.039	-10000	0	-0.86	1	1
BOC	0.016	0	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.13	0.19	-10000	0	-0.63	33	33
STIL	-0.096	0.17	-10000	0	-0.67	10	10
DHH N/PTCH2	-0.045	0.16	-10000	0	-0.63	36	36
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.62	36	36
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
DHH	-0.001	0.11	-10000	0	-0.75	11	11
PTHLH	-0.44	0.41	-10000	0	-0.74	315	315
determination of left/right symmetry	-0.13	0.19	-10000	0	-0.63	33	33
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
skeletal system development	-0.44	0.4	-10000	0	-0.73	315	315
IHH N/Hhip	-0.2	0.31	-10000	0	-0.66	156	156
DHH N/Hhip	-0.15	0.26	-10000	0	-0.58	135	135
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.13	0.19	-10000	0	-0.63	33	33
pancreas development	-0.18	0.33	-10000	0	-0.76	126	126
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.035	-10000	0	-0.56	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.033	0.19	-10000	0	-0.75	32	32
somite specification	-0.13	0.19	-10000	0	-0.63	33	33
SHH Np/Cholesterol/PTCH1	-0.14	0.14	-10000	0	-0.55	36	36
SHH Np/Cholesterol/PTCH2	-0.036	0.13	-10000	0	-0.5	36	36
SHH Np/Cholesterol/Megalin	-0.048	0.15	-10000	0	-0.49	50	50
SHH	0.017	0.088	-10000	0	-0.57	11	11
catabolic process	-0.16	0.19	-10000	0	-0.65	32	32
SMO/Vitamin D3	-0.11	0.18	-10000	0	-0.58	36	36
SHH Np/Cholesterol/Hhip	-0.12	0.21	-10000	0	-0.46	132	132
LRP2	-0.051	0.22	-10000	0	-0.75	44	44
receptor-mediated endocytosis	-0.15	0.18	-10000	0	-0.77	19	19
SHH Np/Cholesterol/BOC	-0.01	0.065	-10000	0	-0.45	11	11
SHH Np/Cholesterol/CDO	-0.071	0.18	-10000	0	-0.52	68	68
mesenchymal cell differentiation	0.12	0.21	0.46	132	-10000	0	132
mol:Vitamin D3	-0.11	0.17	-10000	0	-0.56	36	36
IHH N/PTCH2	-0.085	0.22	-10000	0	-0.62	69	69
CDON	-0.085	0.28	-10000	0	-0.86	58	58
IHH N/PTCH1	-0.16	0.2	-10000	0	-0.66	32	32
Megalin/LRPAP1	-0.049	0.16	-10000	0	-0.56	44	44
PTCH2	-0.028	0.19	-10000	0	-0.86	25	25
SHH Np/Cholesterol	-0.01	0.067	-10000	0	-0.46	11	11
PTCH1	-0.16	0.2	-10000	0	-0.66	32	32
HHIP	-0.18	0.33	-10000	0	-0.76	126	126

×

Fc-epsilon receptor I signaling in mast cells

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.016	0	-9999	-10000	0	0
LAT2	-0.16	0.23	-9999	-0.69	60	60
AP1	-0.16	0.21	-9999	-0.56	82	82
mol:PIP3	-0.24	0.34	-9999	-0.7	139	139
IKBKB	-0.089	0.16	-9999	-0.34	71	71
AKT1	-0.17	0.21	-9999	-0.73	22	22
IKBKG	-0.089	0.16	-9999	-0.34	83	83
MS4A2	-0.19	0.36	-9999	-0.86	113	113
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.035	-9999	-0.75	1	1
MAP3K1	-0.12	0.26	-9999	-0.6	77	77
mol:Ca2+	-0.16	0.24	-9999	-0.48	139	139
LYN	0.011	0.009	-9999	-10000	0	0
CBLB	-0.12	0.15	-9999	-0.54	21	21
SHC1	0.014	0.039	-9999	-0.86	1	1
RasGAP/p62DOK	-0.002	0.031	-9999	-0.48	2	2
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.009	0.078	-9999	-0.86	4	4
PLD2	-0.18	0.28	-9999	-0.92	20	20
PTPN13	-0.07	0.16	-9999	-0.48	23	23
PTPN11	0.014	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.045	0.17	-9999	-0.41	4	4
SYK	0.008	0.049	-9999	-0.76	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.3	0.32	-9999	-0.76	135	135
LAT	-0.26	0.3	-9999	-0.65	154	154
PAK2	-0.15	0.29	-9999	-0.64	110	110
NFATC2	-0.068	0.087	-9999	-0.63	2	2
HRAS	-0.18	0.32	-9999	-0.7	117	117
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.04	0.027	-9999	-10000	0	0
Fc epsilon R1	-0.26	0.32	-9999	-0.62	210	210
Antigen/IgE/Fc epsilon R1	-0.24	0.3	-9999	-0.58	210	210
mol:GDP	-0.21	0.35	-9999	-0.77	123	123
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.008	0.035	-9999	-0.75	1	1
FOS	-0.004	0.12	-9999	-0.76	13	13
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.13	0.16	-9999	-0.57	21	21
CHUK	-0.089	0.16	-9999	-0.34	75	75
KLRG1	-0.12	0.15	-9999	-0.55	21	21
VAV1	-0.2	0.32	-9999	-0.69	130	130
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.15	-9999	-0.54	22	22
negative regulation of mast cell degranulation	-0.11	0.15	-9999	-0.56	23	23
BTK	-0.18	0.24	-9999	-0.63	92	92
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.17	0.22	-9999	-0.58	83	83
GAB2/PI3K/SHP2	-0.19	0.24	-9999	-0.82	22	22
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.12	0.15	-9999	-0.55	21	21
RAF1	0.026	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.31	0.39	-9999	-1	82	82
FCER1G	-0.16	0.34	-9999	-0.87	95	95
FCER1A	-0.023	0.16	-9999	-0.77	22	22
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.28	-9999	-0.55	196	196
MAPK3	0.04	0.026	-9999	-10000	0	0
MAPK1	0.04	0.026	-9999	-10000	0	0
NFKB1	0.014	0.034	-9999	-0.75	1	1
MAPK8	-0.011	0.07	-9999	-10000	0	0
DUSP1	0.014	0.039	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.071	0.074	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.075	0.16	-9999	-0.48	21	21
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.22	0.29	-9999	-0.73	111	111
FER	-0.12	0.16	-9999	-0.55	23	23
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.15	0.19	-9999	-0.42	158	158
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.2	0.36	-9999	-0.76	125	125
cytokine secretion	-0.051	0.053	-9999	-10000	0	0
SPHK1	-0.16	0.22	-9999	-0.65	56	56
PTK2	-0.078	0.16	-9999	-0.5	21	21
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.25	0.31	-9999	-0.77	106	106
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.19	0.31	-9999	-0.68	106	106
MAP2K2	0.035	0.032	-9999	-0.42	1	1
MAP2K1	0.036	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.12	0.15	-9999	-0.53	21	21
MAP2K4	0.017	0.015	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.33	0.4	-9999	-0.73	221	221
mol:Choline	-0.18	0.28	-9999	-0.89	20	20
SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.51	16	16
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.063	0.15	-9999	-0.47	16	16
HCLS1	-0.13	0.18	-9999	-0.67	29	29
PRKCB	-0.14	0.23	-9999	-0.48	113	113
FCGR2B	-0.14	0.34	-9999	-0.86	93	93
IGHE	-0.005	0.01	-9999	-10000	0	0
KLRG1/SHIP	-0.11	0.16	-9999	-0.57	23	23
LCP2	-0.04	0.21	-9999	-0.86	32	32
PLA2G4A	-0.12	0.16	-9999	-0.55	24	24
RASA1	0.014	0.034	-9999	-0.75	1	1
mol:Phosphatidic acid	-0.18	0.28	-9999	-0.89	20	20
IKK complex	-0.048	0.13	-9999	-0.28	1	1
WIPF1	0.016	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.008	0.087	-10000	0	-0.86	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.076	0.2	0.61	31	-0.44	3	34
IL27/IL27R/JAK1	-0.08	0.35	0.57	1	-0.86	55	56
TBX21	-0.2	0.41	0.5	1	-0.76	148	149
IL12B	-0.095	0.28	-10000	0	-0.87	60	60
IL12A	0.008	0.032	-10000	0	-0.68	1	1
IL6ST	-0.013	0.14	-10000	0	-0.76	16	16
IL27RA/JAK1	0.011	0.063	-10000	0	-0.7	1	1
IL27	-0.046	0.22	-10000	0	-0.88	32	32
TYK2	0.011	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.025	0.13	-10000	0	-0.74	2	2
T-helper 2 cell differentiation	0.076	0.2	0.61	31	-0.44	3	34
T cell proliferation during immune response	0.076	0.2	0.61	31	-0.44	3	34
MAPKKK cascade	-0.076	0.2	0.44	3	-0.61	31	34
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.015	0.039	-10000	0	-0.86	1	1
IL12RB1	-0.26	0.41	-10000	0	-0.87	156	156
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.16	0.35	0.5	1	-0.72	92	93
IL27/IL27R/JAK2/TYK2	-0.078	0.2	0.44	3	-0.62	31	34
positive regulation of T cell mediated cytotoxicity	-0.076	0.2	0.44	3	-0.61	31	34
STAT1 (dimer)	-0.065	0.51	0.54	117	-1	66	183
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.081	0.18	0.39	3	-0.62	23	26
T cell proliferation	-0.12	0.25	0.4	1	-0.7	49	50
IL12/IL12R/TYK2/JAK2	-0.18	0.27	-10000	0	-0.75	45	45
IL17A	-0.025	0.13	-10000	0	-0.74	2	2
mast cell activation	0.076	0.2	0.61	31	-0.44	3	34
IFNG	-0.041	0.066	0.12	3	-0.11	230	233
T cell differentiation	-0.011	0.011	0.03	3	-0.026	135	138
STAT3 (dimer)	-0.081	0.18	0.39	3	-0.62	24	27
STAT5A (dimer)	-0.081	0.18	0.39	3	-0.62	23	26
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.75	44	46
STAT4	-0.036	0.21	-10000	0	-0.86	30	30
T cell activation	-0.012	0.008	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.042	0.1	-10000	0	-0.64	2	2
GATA3	-0.61	0.68	-10000	0	-1.3	244	244
IL18	0.005	0.081	-10000	0	-0.68	7	7
positive regulation of mast cell cytokine production	-0.08	0.18	0.38	3	-0.6	24	27
IL27/EBI3	-0.12	0.33	-10000	0	-0.83	83	83
IL27RA	-0.003	0.063	-10000	0	-0.75	1	1
IL6	-0.087	0.28	-10000	0	-0.81	63	63
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0	0.088	0.41	1	-0.59	10	11
IL1B	0.006	0.073	-10000	0	-0.66	6	6
EBI3	-0.12	0.31	-10000	0	-0.88	73	73
TNF	0.004	0.08	-10000	0	-0.63	8	8

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.007	0.073	-9999	-0.66	6	6
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.021	0.12	-9999	-0.66	16	16
STXBP1	0.014	0.034	-9999	-0.75	1	1
ACh/CHRNA1	-0.28	0.31	-9999	-0.63	224	224
RAB3GAP2/RIMS1/UNC13B	-0.018	0.1	-9999	-0.57	16	16
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	-0.016	0.15	-9999	-0.86	16	16
mol:ACh	-0.009	0.053	-9999	-0.13	77	77
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.039	0.1	-9999	-0.62	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.28	0.31	-9999	-0.62	224	224
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.37	0.44	-9999	-0.86	224	224
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.083	0.2	-9999	-0.54	82	82
SNAP25	-0.038	0.12	-9999	-0.33	73	73
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.11	0.28	-9999	-0.75	82	82
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.008	0.065	-9999	-0.56	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.039	0.1	-9999	-0.62	4	4

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.19	0.35	-10000	0	-1.1	67	67
NFATC2	-0.08	0.24	-10000	0	-0.77	13	13
NFATC3	-0.021	0.064	-10000	0	-10000	0	0
CD40LG	-0.24	0.44	-10000	0	-1.1	57	57
ITCH	0.054	0.059	-10000	0	-10000	0	0
CBLB	0.054	0.059	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.55	0.56	-10000	0	-1.2	188	188
JUNB	0.013	0.048	-10000	0	-0.75	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.059	-10000	0	-10000	0	0
T cell anergy	0.022	0.095	-10000	0	-0.6	1	1
TLE4	-0.03	0.17	-10000	0	-0.75	5	5
Jun/NFAT1-c-4/p21SNFT	-0.24	0.27	-10000	0	-1	24	24
AP-1/NFAT1-c-4	-0.3	0.37	-10000	0	-1.2	38	38
IKZF1	-0.13	0.36	-10000	0	-0.89	90	90
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.74	95	95
AP-1/NFAT1	-0.094	0.16	-10000	0	-0.68	12	12
CALM1	0.028	0.037	-10000	0	-10000	0	0
EGR2	-0.1	0.28	-10000	0	-1.3	8	8
EGR3	-0.11	0.29	-10000	0	-1.5	7	7
NFAT1/FOXP3	-0.29	0.4	-10000	0	-0.99	99	99
EGR1	0.001	0.11	-10000	0	-0.74	11	11
JUN	0.006	0.022	-10000	0	-10000	0	0
EGR4	0.006	0.078	-10000	0	-0.86	4	4
mol:Ca2+	0.009	0.041	-10000	0	-10000	0	0
GBP3	-0.034	0.18	-10000	0	-0.86	7	7
FOSL1	-0.026	0.19	-10000	0	-0.86	24	24
NFAT1-c-4/MAF/IRF4	-0.27	0.36	-10000	0	-0.91	94	94
DGKA	-0.034	0.19	-10000	0	-1.1	6	6
CREM	0.015	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.21	-10000	0	-1.1	6	6
CTLA4	-0.44	0.58	-10000	0	-1	234	234
NFAT1-c-4 (dimer)/EGR1	-0.17	0.24	-10000	0	-1.1	11	11
NFAT1-c-4 (dimer)/EGR4	-0.17	0.22	-10000	0	-1.1	7	7
FOS	-0.014	0.12	-10000	0	-0.76	13	13
IFNG	-0.49	0.51	-10000	0	-1	224	224
T cell activation	-0.049	0.22	-10000	0	-0.82	16	16
MAF	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.063	0.2	0.91	3	-10000	0	3
TNF	-0.095	0.28	-10000	0	-1.1	12	12
FASLG	-0.33	0.47	-10000	0	-0.97	61	61
TBX21	-0.3	0.43	-10000	0	-0.93	160	160
BATF3	-0.062	0.25	-10000	0	-0.86	45	45
PRKCQ	-0.034	0.13	-10000	0	-0.75	15	15
PTPN1	-0.03	0.17	-10000	0	-0.84	3	3
NFAT1-c-4/ICER1	-0.17	0.21	-10000	0	-1.2	5	5
GATA3	-0.35	0.38	-10000	0	-0.75	244	244
T-helper 1 cell differentiation	-0.48	0.5	-10000	0	-0.99	224	224
IL2RA	-0.39	0.46	-10000	0	-1.1	126	126
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.03	0.17	-10000	0	-0.75	5	5
E2F1	-0.081	0.28	-10000	0	-0.85	61	61
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.03	0.17	-10000	0	-0.75	5	5
IRF4	-0.18	0.37	-10000	0	-0.86	116	116
PTGS2	-0.21	0.4	-10000	0	-1.1	33	33
CSF2	-0.21	0.4	-10000	0	-1.1	32	32
JunB/Fra1/NFAT1-c-4	-0.17	0.22	-10000	0	-0.96	10	10
IL4	-0.36	0.29	-10000	0	-0.78	88	88
IL5	-0.2	0.38	-10000	0	-1	26	26
IL2	-0.05	0.22	-10000	0	-0.84	16	16
IL3	-0.05	0.049	-10000	0	-10000	0	0
RNF128	0.032	0.16	-10000	0	-0.79	19	19
NFATC1	-0.063	0.2	-10000	0	-0.91	3	3
CDK4	0.034	0.18	-10000	0	-10000	0	0
PTPRK	-0.03	0.17	-10000	0	-0.75	5	5
IL8	-0.22	0.42	-10000	0	-1.1	40	40
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

S1P1 pathway

Figure S31. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S31. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.66	225	225
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.029	0.1	-9999	-0.36	41	41
mol:S1P	-0.023	0.093	-9999	-0.36	14	14
S1P1/S1P/Gi	-0.044	0.14	-9999	-0.5	12	12
GNAO1	0.009	0.085	-9999	-0.84	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.053	0.084	-9999	-0.66	1	1
PLCG1	-0.026	0.13	-9999	-0.49	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.004	-9999	-10000	0	0
GNAI2	0.018	0.005	-9999	-10000	0	0
GNAI3	0.015	0.006	-9999	-10000	0	0
GNAI1	0.01	0.059	-9999	-0.75	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.24	0.3	-9999	-0.58	225	225
S1P1/S1P	-0.2	0.21	-9999	-0.42	226	226
negative regulation of cAMP metabolic process	-0.043	0.14	-9999	-0.48	12	12
MAPK3	-0.035	0.16	-9999	-0.56	23	23
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.014	0.034	-9999	-0.75	1	1
PLCB2	-0.19	0.26	-9999	-0.67	56	56
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.17	-9999	-0.5	21	21
receptor internalization	-0.19	0.19	-9999	-0.39	226	226
PTGS2	-0.044	0.23	-9999	-0.98	24	24
Rac1/GTP	-0.17	0.17	-9999	-0.5	21	21
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.37	0.44	-9999	-0.86	225	225
negative regulation of T cell proliferation	-0.043	0.14	-9999	-0.48	12	12
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.01	0.059	-9999	-0.75	3	3
MAPK1	-0.035	0.16	-9999	-0.56	23	23
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.62	21	21
ABCC1	0.016	0.002	-9999	-10000	0	0

×

Ephrin A reverse 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.055	0.16	-9999	-0.53	53	53
EFNA5	-0.056	0.22	-9999	-0.76	47	47
FYN	-0.026	0.16	-9999	-0.48	53	53
neuron projection morphogenesis	-0.055	0.16	-9999	-0.53	53	53
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.056	0.17	-9999	-0.53	53	53
EPHA5	-0.008	0.11	-9999	-0.86	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.043	-9999	-0.49	4	4
ARNO/beta Arrestin1-2	-0.017	0.062	-9999	-10000	0	0
EGFR	0	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.034	-9999	-0.75	1	1
USP6	0.014	0.039	-9999	-0.86	1	1
IQSEC1	0.015	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.51	0.18	-9999	-0.57	456	456
ARRB2	-0.013	0.1	-9999	-0.39	36	36
mol:GTP	-0.01	0.048	-9999	-0.23	2	2
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.085	0.28	-9999	-0.86	58	58
EGF	-0.67	0.23	-9999	-0.75	455	455
somatostatin receptor activity	0	0	-9999	-0.001	18	18
ARAP2	0.013	0.048	-9999	-0.75	2	2
mol:GDP	-0.056	0.093	-9999	-0.33	23	23
mol:PI-3-4-5-P3	0	0	-9999	-0.001	7	7
ITGA2B	-0.015	0.16	-9999	-0.86	18	18
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.035	-9999	-0.52	1	1
ADAP1	0.01	0.068	-9999	-0.75	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.034	0.15	-9999	-0.66	26	26
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.086	0.089	-9999	-0.33	21	21
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.44	0.16	-9999	-0.49	456	456
ADRB2	0.013	0.048	-9999	-0.75	2	2
receptor agonist activity	0	0	-9999	0	14	14
actin filament binding	0	0	-9999	-0.001	18	18
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.011	0.059	-9999	-0.75	3	3
GNAQ	0.015	0.002	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	10	10
ARF6/GDP	-0.066	0.14	-9999	-0.4	5	5
ARF6/GDP/GULP/ACAP1	-0.22	0.26	-9999	-0.53	190	190
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.021	0.1	-9999	-0.52	17	17
ACAP1	-0.31	0.42	-9999	-0.86	188	188
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.042	0.15	-9999	-0.59	36	36
EFNA1	0.014	0.039	-9999	-0.86	1	1
HGF	-0.022	0.17	-9999	-0.8	23	23
CYTH3	0.015	0	-9999	-10000	0	0
CYTH2	0.01	0.001	-9999	-10000	0	0
NCK1	0.014	0.034	-9999	-0.75	1	1
fibronectin binding	0	0	-9999	-0.001	11	11
endosomal lumen acidification	0	0	-9999	-0.001	20	20
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.011	0.14	-9999	-0.75	18	18
GNAQ/ARNO	0.009	0.01	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	2	2
MET	0.007	0.087	-9999	-0.86	5	5
GNA14	0.005	0.089	-9999	-0.75	7	7
GNA15	-0.009	0.14	-9999	-0.86	14	14
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	10	10
GNA11	0.012	0.048	-9999	-0.75	2	2
LHCGR	-0.054	0.22	-9999	-0.86	35	35
AGTR1	-0.027	0.18	-9999	-0.75	28	28
desensitization of G-protein coupled receptor protein signaling pathway	-0.042	0.15	-9999	-0.59	36	36
IPCEF1/ARNO	-0.34	0.13	-9999	-0.82	8	8
alphaIIb/beta3 Integrin	-0.027	0.13	-9999	-0.64	21	21

×

Calcium signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.047	-9999	-10000	0	0
NFATC2	-0.016	0.06	-9999	-0.6	2	2
NFATC3	-0.013	0.047	-9999	-10000	0	0
CD40LG	-0.3	0.42	-9999	-0.94	98	98
PTGS2	-0.29	0.39	-9999	-0.86	92	92
JUNB	0.013	0.048	-9999	-0.75	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.02	0.018	-9999	-10000	0	0
CaM/Ca2+	-0.02	0.018	-9999	-10000	0	0
CALM1	0.006	0.013	-9999	-10000	0	0
JUN	0.006	0.013	-9999	-10000	0	0
mol:Ca2+	-0.02	0.019	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.003	-9999	-10000	0	0
FOSL1	-0.026	0.19	-9999	-0.86	24	24
CREM	0.015	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.73	35	35
FOS	-0.014	0.12	-9999	-0.76	13	13
IFNG	-0.44	0.52	-9999	-0.98	218	218
AP-1/NFAT1-c-4	-0.41	0.41	-9999	-1.1	92	92
FASLG	-0.46	0.52	-9999	-0.98	221	221
NFAT1-c-4/ICER1	-0.079	0.078	-9999	-0.56	2	2
IL2RA	-0.34	0.45	-9999	-1	103	103
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.28	0.38	-9999	-0.87	90	90
JunB/Fra1/NFAT1-c-4	-0.093	0.12	-9999	-0.57	17	17
IL4	-0.28	0.37	-9999	-0.83	87	87
IL2	-0.012	0.11	-9999	-0.76	10	10
IL3	-0.028	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.062	0.25	-9999	-0.86	45	45
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.025	-9999	-0.56	1	1
Necdin/E2F1	-0.083	0.22	-9999	-0.68	62	62
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.077	0.2	-9999	-0.98	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.3	-9999	-0.56	241	241
NT-4/5 (dimer)/p75(NTR)	-0.05	0.18	-9999	-0.67	38	38
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.031	0.22	-9999	-0.95	9	9
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.1	0.3	-9999	-0.86	68	68
MGDIs/NGR/p75(NTR)/LINGO1	-0.07	0.2	-9999	-0.61	58	58
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.11	0.24	-9999	-0.61	95	95
LINGO1	-0.022	0.18	-9999	-0.86	22	22
Sortilin/TRAF6/NRIF	-0.001	0.015	-9999	-10000	0	0
proBDNF (dimer)	-0.1	0.3	-9999	-0.86	68	68
NTRK1	-0.045	0.21	-9999	-0.76	39	39
RTN4R	0.004	0.1	-9999	-0.84	7	7
neuron apoptosis	-0.065	0.23	-9999	-0.67	29	29
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.058	0.24	-9999	-0.63	73	73
ARHGDIA	0.014	0.034	-9999	-0.75	1	1
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.083	0.21	-9999	-0.58	71	71
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.085	0.21	-9999	-0.58	72	72
Mammalian IAPs/DIABLO	-0.08	0.19	-9999	-0.52	78	78
proNGF (dimer)	-0.065	0.25	-9999	-0.86	47	47
MAGED1	0.014	0.039	-9999	-0.86	1	1
APP	0.014	0.034	-9999	-0.75	1	1
NT-4/5 (dimer)	-0.003	0.086	-9999	-0.86	5	5
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.078	0.2	-9999	-0.54	71	71
NGF	-0.066	0.25	-9999	-0.86	47	47
cell cycle arrest	-0.011	0.25	-9999	-0.56	71	71
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.044	0.11	-9999	-0.57	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.044	0.15	-9999	-0.58	38	38
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.089	0.23	-9999	-0.63	72	72
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.043	0.22	-9999	-0.57	71	71
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.034	0.086	-9999	-0.44	8	8
p75(NTR)/beta APP	-0.044	0.17	-9999	-0.66	34	34
BEX1	-0.27	0.37	-9999	-0.75	187	187
mol:GDP	-0.07	0.24	-9999	-0.64	72	72
NGF (dimer)	-0.35	0.3	-9999	-0.84	86	86
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.064	0.18	-9999	-0.56	58	58
PIK3R1	0.014	0.034	-9999	-0.75	1	1
RAC1/GTP	-0.079	0.2	-9999	-0.56	72	72
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.09	0.23	-9999	-0.63	72	72
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.08	0.22	-9999	-0.66	61	61
NT3 (dimer)	0.005	0.093	-9999	-0.78	7	7
TP53	-0.04	0.22	-9999	-0.91	7	7
PRDM4	-0.043	0.22	-9999	-0.57	71	71
BDNF (dimer)	-0.42	0.36	-9999	-0.88	138	138
PIK3CA	0.014	0.034	-9999	-0.75	1	1
SORT1	0.014	0.034	-9999	-0.75	1	1
activation of caspase activity	-0.076	0.19	-9999	-0.96	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.083	0.21	-9999	-0.58	71	71
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.022	0.21	-9999	-0.63	22	22
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.043	0.22	-9999	-0.57	71	71
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.091	0.23	-9999	-0.63	73	73
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.051	0.18	-9999	-0.66	39	39
MAPK8	-0.02	0.2	-9999	-0.63	21	21
MAPK9	-0.02	0.2	-9999	-0.63	21	21
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.005	0.093	-9999	-0.78	7	7
NTF4	-0.003	0.086	-9999	-0.86	5	5
NDN	0.011	0.059	-9999	-0.75	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.07	0.18	-9999	-0.91	8	8
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.019	-9999	-10000	0	0
RhoA-B-C/GTP	-0.089	0.23	-9999	-0.62	72	72
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.097	0.21	-9999	-0.97	7	7
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.22	-9999	-0.56	93	93
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.089	0.23	-9999	-0.66	68	68
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	78	78
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	0.009	0.24	-9999	-0.54	56	56
BAD	-0.009	0.2	-9999	-0.59	21	21
RIPK2	0.014	0.039	-9999	-0.86	1	1
NGFR	-0.042	0.22	-9999	-0.86	33	33
CYCS	-0.033	0.22	-9999	-0.96	9	9
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.083	0.21	-9999	-0.58	72	72
BCL2L11	-0.008	0.2	-9999	-0.59	21	21
BDNF (dimer)/p75(NTR)	-0.13	0.28	-9999	-0.7	95	95
PI3K	-0.083	0.21	-9999	-0.58	71	71
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.083	0.21	-9999	-0.58	71	71
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.1	0.26	-9999	-0.72	72	72
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.084	0.21	-9999	-0.58	72	72
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.059	-9999	-0.75	3	3
PLG	-0.39	0.38	-9999	-0.75	265	265
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.12	0.23	-9999	-0.68	41	41
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.003	0.18	-9999	-0.53	21	21
E2F1	-0.09	0.29	-9999	-0.86	61	61
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.07	0.15	-9999	-0.59	13	13
NGF (dimer)/TRKA	-0.1	0.24	-9999	-0.63	84	84
MMP7	-0.12	0.3	-9999	-0.76	90	90
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.077	0.2	-9999	-0.54	71	71
MMP3	-0.071	0.25	-9999	-0.86	46	46
APAF-1/Caspase 9	-0.11	0.17	-9999	-0.69	10	10

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.046	0.14	-9999	-0.73	1	1
CCNA2	-0.16	0.35	-9999	-0.86	100	100
PIK3CA	0.015	0.034	-9999	-0.75	1	1
JAK3	-0.16	0.36	-9999	-0.86	104	104
PIK3R1	0.015	0.034	-9999	-0.75	1	1
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.11	0.25	-9999	-0.66	58	58
SHC1	0.015	0.039	-9999	-0.86	1	1
SP1	0.024	0.022	-9999	-10000	0	0
IL2RA	-0.12	0.33	-9999	-0.77	103	103
IL2RB	-0.45	0.44	-9999	-0.86	267	267
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.042	0.22	-9999	-0.86	34	34
G1/S transition of mitotic cell cycle	-0.047	0.2	-9999	-0.53	17	17
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.051	-9999	-0.77	2	2
LCK	-0.021	0.18	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.007	0.12	-9999	-0.86	10	10
CDK6	0.014	0.034	-9999	-0.75	1	1
CCND3	-0.079	0.21	-9999	-0.66	28	28

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.12	0.24	-10000	0	-0.76	36	36
UGCG	-0.023	0.047	-10000	0	-0.84	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.082	0.19	-10000	0	-0.49	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.009	0.057	-10000	0	-0.83	1	1
mol:DAG	-0.004	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.11	0.16	-10000	0	-0.56	35	35
FRAP1	-0.086	0.23	-10000	0	-0.62	48	48
FOXO3	-0.077	0.22	-10000	0	-0.66	32	32
AKT1	-0.094	0.24	-10000	0	-0.64	51	51
GAB2	0.016	0.003	-10000	0	-10000	0	0
SMPD1	-0.021	0.03	-10000	0	-10000	0	0
SGMS1	-0.021	0.03	-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	0.026	0.033	-10000	0	-0.48	2	2
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.023	0.098	-10000	0	-0.43	2	2
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.035	-10000	0	-0.56	2	2
RPS6KB1	-0.029	0.088	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.006	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.16	0.36	-10000	0	-0.86	104	104
PIK3R1	0.017	0.034	-10000	0	-0.74	1	1
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.034	-10000	0	-0.75	1	1
MYC	-0.077	0.22	-10000	0	-0.66	34	34
MYB	-0.19	0.34	-10000	0	-0.73	139	139
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.12	0.26	-10000	0	-0.68	61	61
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.037	0.068	-10000	0	-0.47	2	2
mol:PI-3-4-5-P3	-0.12	0.25	-10000	0	-0.66	61	61
Rac1/GDP	0.01	0.033	-10000	0	-0.43	2	2
T cell proliferation	-0.098	0.24	-10000	0	-0.64	51	51
SHC1	0.014	0.039	-10000	0	-0.86	1	1
RAC1	0.015	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.009	0.026	-10000	0	-0.05	139	139
PRKCZ	-0.1	0.25	-10000	0	-0.67	51	51
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.58	29	29
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.15	0.26	-10000	0	-0.58	100	100
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.16	0.35	-10000	0	-0.86	102	102
IL2RB	-0.44	0.44	-10000	0	-0.86	267	267
TERT	-0.11	0.3	-10000	0	-0.86	70	70
E2F1	-0.1	0.2	-10000	0	-0.37	175	175
SOS1	0.016	0.003	-10000	0	-10000	0	0
RPS6	0.012	0.055	-10000	0	-0.86	2	2
mol:cAMP	0.004	0.013	0.025	139	-10000	0	139
PTPN11	0.016	0.003	-10000	0	-10000	0	0
IL2RG	-0.04	0.22	-10000	0	-0.86	34	34
actin cytoskeleton organization	-0.098	0.24	-10000	0	-0.64	51	51
GRB2	0.016	0.003	-10000	0	-10000	0	0
IL2	-0.005	0.12	-10000	0	-0.86	10	10
PIK3CA	0.017	0.034	-10000	0	-0.74	1	1
Rac1/GTP	0.031	0.035	-10000	0	-0.41	2	2
LCK	-0.019	0.18	-10000	0	-0.85	22	22
BCL2	-0.053	0.18	-10000	0	-0.53	24	24

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.026	0.023	-9999	-0.49	1	1
ADCY5	0.005	0.1	-9999	-0.49	22	22
ADCY6	0.025	0.043	-9999	-0.93	1	1
ADCY7	0.008	0.11	-9999	-0.58	16	16
ADCY1	0.014	0.084	-9999	-0.5	13	13
ADCY2	-0.13	0.26	-9999	-0.58	131	131
ADCY3	0.026	0.023	-9999	-0.49	1	1
ADCY8	-0.16	0.28	-9999	-0.58	157	157
PRKCE	0.014	0.026	-9999	-0.57	1	1
ADCY9	0.026	0.023	-9999	-0.49	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.091	0.17	-9999	-0.5	50	50

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0	0.058	0.29	18	-10000	0	18
BUB1B	-0.024	0.12	-10000	0	-0.5	26	26
PLK1	-0.012	0.059	-10000	0	-0.2	10	10
PLK1S1	0.001	0.031	-10000	0	-10000	0	0
KIF2A	-0.004	0.073	-10000	0	-0.56	4	4
regulation of mitotic centrosome separation	-0.013	0.059	-10000	0	-0.2	10	10
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.18	0.33	-10000	0	-0.71	124	124
WEE1	-0.002	0.056	-10000	0	-0.32	2	2
cytokinesis	-0.2	0.27	-10000	0	-0.5	232	232
PP2A-alpha B56	-0.14	0.16	-10000	0	-10000	0	0
AURKA	-0.003	0.045	-10000	0	-0.29	6	6
PICH/PLK1	-0.045	0.16	-10000	0	-0.84	18	18
CENPE	-0.065	0.21	-10000	0	-0.62	60	60
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.004	0.072	-10000	0	-0.55	4	4
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.034	-10000	0	-0.75	1	1
TPX2	-0.051	0.12	-10000	0	-0.25	125	125
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.073	0.26	-10000	0	-0.86	51	51
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.026	0.096	-10000	0	-0.28	58	58
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.004	0.009	-10000	0	-0.02	128	128
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.006	0.031	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0.001	0.002	-10000	0	-0.014	6	6
STAG2	0.016	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.009	0.013	-10000	0	-10000	0	0
spindle elongation	-0.013	0.059	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.17	0.19	-10000	0	-0.46	9	9
TPT1	0.001	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	235	235
CDC25B	0.007	0.088	-10000	0	-0.88	5	5
SGOL1	0	0.058	-10000	0	-0.29	18	18
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.024	0.1	-10000	0	-0.74	9	9
CDC14B	0.016	0.002	-10000	0	-10000	0	0
CDC20	-0.057	0.24	-10000	0	-0.86	42	42
PLK1/PBIP1	-0.042	0.12	-10000	0	-0.59	18	18
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.002	0.045	-10000	0	-0.21	2	2
CDC2	-0.001	0.004	-10000	0	-0.023	9	9
NDC80	-0.17	0.36	-10000	0	-0.86	108	108
metaphase plate congression	-0.005	0.041	-10000	0	-10000	0	0
ERCC6L	-0.037	0.16	-10000	0	-0.82	18	18
NLP/gamma Tubulin	-0.003	0.035	-10000	0	-0.12	5	5
microtubule cytoskeleton organization	0.001	0.031	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.016	0.002	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.26	0.29	-10000	0	-0.56	232	232
GRASP65/GM130/RAB1/GTP/PLK1	-0.014	0.027	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.038	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	119	119
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.043	-10000	0	-10000	0	0
microtubule-based process	-0.25	0.31	-10000	0	-0.58	232	232
Golgi organization	-0.013	0.059	-10000	0	-0.2	10	10
Cohesin/SA2	-0.025	0.045	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.39	0.44	-10000	0	-0.86	232	232
APC/C/CDC20	-0.047	0.18	-10000	0	-0.64	42	42
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.041	0.11	-10000	0	-0.57	18	18
PRC1	0.005	0.095	-10000	0	-0.86	6	6
ECT2	0	0.053	-10000	0	-10000	0	0
C13orf34	0.003	0.043	-10000	0	-10000	0	0
NUDC	-0.005	0.041	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.024	0.12	-10000	0	-0.5	26	26
spindle assembly	-0.007	0.048	-10000	0	-0.16	8	8
spindle stabilization	0.001	0.031	-10000	0	-10000	0	0
APC/C/HCDH1	-0.001	0.022	-10000	0	-0.49	1	1
MKLP2/PLK1	-0.25	0.31	-10000	0	-0.59	232	232
CCNB1	0.001	0.11	-10000	0	-0.87	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.005	0.049	-10000	0	-0.46	2	2
TUBG1	0.001	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.026	0.099	-10000	0	-0.71	9	9
MLF1IP	-0.012	0.13	-10000	0	-0.69	18	18
INCENP	0.009	0.008	-10000	0	-10000	0	0

×

BCR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.054	0.17	-10000	0	-0.42	37	37
IKBKB	-0.024	0.1	-10000	0	-10000	0	0
AKT1	-0.024	0.13	-10000	0	-0.32	4	4
IKBKG	-0.024	0.11	-10000	0	-0.3	3	3
CALM1	-0.042	0.1	-10000	0	-0.5	3	3
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
MAP3K1	-0.11	0.25	-10000	0	-0.63	69	69
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.11	-10000	0	-0.5	4	4
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.012	0.09	-10000	0	-0.26	2	2
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.034	-10000	0	-0.75	1	1
SHC1	0.014	0.039	-10000	0	-0.86	1	1
BCR complex	-0.17	0.3	-10000	0	-0.68	126	126
CD22	-0.15	0.23	-10000	0	-0.67	51	51
CAMK2G	-0.03	0.098	-10000	0	-0.49	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.009	0.078	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.11	0.19	-10000	0	-0.84	4	4
GO:0007205	-0.056	0.11	-10000	0	-0.5	4	4
SYK	0.013	0.048	-10000	0	-0.75	2	2
ELK1	-0.043	0.1	-10000	0	-0.5	3	3
NFATC1	-0.072	0.2	-10000	0	-0.5	64	64
B-cell antigen/BCR complex	-0.17	0.3	-10000	0	-0.68	126	126
PAG1/CSK	-0.003	0.042	-10000	0	-0.66	2	2
NFKBIB	0.004	0.039	-10000	0	-0.13	1	1
HRAS	-0.038	0.12	-10000	0	-0.49	4	4
NFKBIA	0.005	0.038	-10000	0	-0.14	1	1
NF-kappa-B/RelA/I kappa B beta	0.013	0.032	-10000	0	-0.18	1	1
RasGAP/Csk	-0.21	0.32	-10000	0	-0.99	45	45
mol:GDP	-0.051	0.1	0.29	1	-0.47	4	5
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	0.011	0.067	-10000	0	-0.86	3	3
NF-kappa-B/RelA/I kappa B alpha	0.013	0.032	-10000	0	-0.19	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.08	0.22	-10000	0	-0.57	62	62
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
mol:IP3	-0.066	0.1	0.27	1	-0.51	4	5
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.041	0.11	-10000	0	-0.48	6	6
CHUK	-0.024	0.11	-10000	0	-0.3	2	2
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.13	0.2	-10000	0	-0.54	81	81
PTPN6	-0.14	0.21	-10000	0	-0.68	38	38
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.011	0.068	-10000	0	-0.14	104	104
VAV2	-0.17	0.28	-10000	0	-0.8	71	71
ubiquitin-dependent protein catabolic process	0.01	0.037	-10000	0	-0.12	1	1
BTK	-0.087	0.17	0.46	1	-0.41	103	104
CD19	-0.19	0.33	-10000	0	-0.89	76	76
MAP4K1	-0.33	0.43	-10000	0	-0.86	201	201
CD72	-0.19	0.37	-10000	0	-0.86	118	118
PAG1	0.012	0.055	-10000	0	-0.86	2	2
MAPK14	-0.084	0.22	-10000	0	-0.53	60	60
SH3BP5	0.014	0.034	-10000	0	-0.75	1	1
PIK3AP1	-0.038	0.11	-10000	0	-0.54	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.11	0.23	-10000	0	-0.6	65	65
RAF1	-0.026	0.11	-10000	0	-0.53	2	2
RasGAP/p62DOK/SHIP	-0.2	0.31	-10000	0	-0.97	46	46
CD79A	-0.2	0.38	-10000	0	-0.86	126	126
re-entry into mitotic cell cycle	-0.012	0.09	-10000	0	-0.26	2	2
RASA1	0.014	0.034	-10000	0	-0.75	1	1
MAPK3	-0.002	0.1	-10000	0	-10000	0	0
MAPK1	-0.002	0.1	-10000	0	-0.42	2	2
CD72/SHP1	-0.23	0.33	-10000	0	-0.82	97	97
NFKB1	0.014	0.034	-10000	0	-0.75	1	1
MAPK8	-0.084	0.22	-10000	0	-0.53	60	60
actin cytoskeleton organization	-0.098	0.26	-10000	0	-0.67	65	65
NF-kappa-B/RelA	0.034	0.059	-10000	0	-10000	0	0
Calcineurin	-0.043	0.07	-10000	0	-10000	0	0
PI3K	-0.14	0.22	-10000	0	-0.6	67	67
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.062	0.1	-10000	0	-0.55	4	4
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.27	0.32	-10000	0	-0.74	131	131
DAPP1	-0.11	0.18	-10000	0	-0.61	35	35
cytokine secretion	-0.066	0.19	-10000	0	-0.46	64	64
mol:DAG	-0.066	0.1	0.27	1	-0.51	4	5
PLCG2	0.003	0.1	-10000	0	-0.82	8	8
MAP2K1	-0.014	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.25	0.37	-10000	0	-0.72	174	174
mol:PI-3-4-5-P3	-0.098	0.15	-10000	0	-0.42	41	41
ETS1	-0.018	0.092	-10000	0	-0.44	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.22	-10000	0	-0.98	3	3
B-cell antigen/BCR complex/LYN	-0.14	0.22	-10000	0	-0.57	69	69
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.11	0.28	-10000	0	-0.73	65	65
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.25	-10000	0	-0.67	62	62
CARD11	-0.15	0.26	-10000	0	-0.62	108	108
FCGR2B	-0.14	0.34	-10000	0	-0.86	93	93
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.005	0.047	-10000	0	-10000	0	0
PTPRC	-0.08	0.27	-10000	0	-0.86	55	55
PDPK1	-0.061	0.1	-10000	0	-0.37	2	2
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	0	0.058	-10000	0	-0.14	64	64

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.013	0.036	-9999	-0.79	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.023	-9999	-10000	0	0
JMJD2C	0	0.021	-9999	-0.11	17	17
T-DHT/AR/Ubc9	-0.077	0.11	-9999	-0.55	24	24
CARM1	0.015	0.003	-9999	-10000	0	0
PRDX1	0.016	0.001	-9999	-10000	0	0
PELP1	0.016	0.003	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
AKT1	0.017	0.006	-9999	-10000	0	0
PTK2B	0.015	0.003	-9999	-10000	0	0
MED1	0.014	0.009	-9999	-10000	0	0
MAK	0.014	0.045	-9999	-0.86	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.01	0.062	-9999	-0.78	3	3
GSN	0.015	0.008	-9999	-10000	0	0
NCOA2	0.003	0.095	-9999	-0.75	8	8
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.026	-9999	-10000	0	0
NCOA4	0.015	0.002	-9999	-10000	0	0
PIAS3	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.028	0.037	-9999	-0.61	1	1
XRCC5	0.016	0.005	-9999	-10000	0	0
UBE3A	0.014	0.013	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.093	0.14	-9999	-0.58	37	37
FHL2	-0.04	0.11	-9999	-1.1	5	5
RANBP9	0.016	0.003	-9999	-10000	0	0
JMJD1A	-0.12	0.056	-9999	-0.14	437	437
CDK6	0.014	0.034	-9999	-0.75	1	1
TGFB1I1	0.013	0.039	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.15	-9999	-0.6	43	43
XRCC6	0.016	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.59	24	24
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.015	0.017	-9999	-10000	0	0
BRCA1	0.015	0.007	-9999	-10000	0	0
TCF4	0.014	0.013	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	487	487
SRF	0.026	0.012	-9999	-10000	0	0
NKX3-1	-0.19	0.07	-9999	-10000	0	0
KLK3	0.024	0.15	-9999	-0.7	20	20
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.013	-9999	-10000	0	0
AOF2	-0.001	0.01	-9999	-10000	0	0
APPL1	0.033	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.076	0.11	-9999	-0.54	24	24
AR	-0.069	0.16	-9999	-0.79	24	24
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.014	0.013	-9999	-10000	0	0
PAWR	0.014	0.034	-9999	-0.75	1	1
PRKDC	0.016	0.005	-9999	-10000	0	0
PA2G4	0.014	0.012	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.1	-9999	-0.5	24	24
RPS6KA3	0.013	0.036	-9999	-0.79	1	1
T-DHT/AR/ARA70	-0.078	0.11	-9999	-0.55	24	24
LATS2	0.014	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.068	0.1	-9999	-0.5	24	24
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.006	0.13	-9999	-0.75	14	14
KLK2	-0.083	0.14	-9999	-0.8	17	17
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.067	0.12	-9999	-0.59	21	21
TMPRSS2	-0.92	0.36	-9999	-1.1	437	437
CCND1	-0.018	0.17	-9999	-0.86	19	19
PIAS1	0.014	0.013	-9999	-10000	0	0
mol:T-DHT	-0.062	0.027	-9999	-0.072	427	427
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.013	0.019	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.11	-9999	-0.56	24	24
CMTM2	-0.005	0.13	-9999	-0.86	12	12
SNURF	-0.009	0.13	-9999	-0.75	16	16
ZMIZ1	-0.031	0.022	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.014	0.013	-9999	-10000	0	0
FKBP4	0.016	0.003	-9999	-10000	0	0

×

IL6-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
BCL2L1	-0.14	0.3	-9999	-0.71	55	55
CRP	-0.2	0.39	-9999	-0.91	88	88
cell cycle arrest	-0.17	0.35	-9999	-0.78	80	80
TIMP1	-0.15	0.33	-9999	-0.77	67	67
IL6ST	-0.012	0.13	-9999	-0.74	16	16
Rac1/GDP	-0.14	0.26	-9999	-0.59	85	85
AP1	0.021	0.11	-9999	-0.55	3	3
GAB2	0.011	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.37	-9999	-0.84	80	80
HSP90B1	0.005	0.088	-9999	-10000	0	0
GAB1	0.014	0.006	-9999	-10000	0	0
MAPK14	0.018	0.13	-9999	-0.69	3	3
AKT1	0.06	0.035	-9999	-10000	0	0
FOXO1	0.076	0.024	-9999	-10000	0	0
MAP2K6	-0.016	0.14	-9999	-0.68	4	4
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.27	-9999	-0.64	68	68
MITF	-0.023	0.14	-9999	-0.8	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	0.028	0.005	-9999	-10000	0	0
CEBPB	0.002	0.13	-9999	-0.86	12	12
GRB2/SOS1/GAB family/SHP2	0.001	0.069	-9999	-10000	0	0
STAT3	-0.18	0.36	-9999	-0.82	80	80
STAT1	-0.005	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.31	-9999	-0.75	42	42
PIK3CA	0.016	0.034	-9999	-0.75	1	1
PI3K	-0.002	0.035	-9999	-0.56	2	2
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.017	0.13	-9999	-0.75	2	2
MAPK11	0.017	0.13	-9999	-0.7	4	4
STAT3 (dimer)/FOXO1	-0.07	0.27	-9999	-0.64	21	21
GRB2/SOS1/GAB family	-0.046	0.11	-9999	-0.67	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.038	0.15	-9999	-0.63	12	12
GRB2	0.014	0.006	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	-0.28	0.45	-9999	-0.88	158	158
PIK3R1	0.016	0.034	-9999	-0.75	1	1
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.32	-9999	-0.79	48	48
FGG	-0.27	0.43	-9999	-0.85	136	136
macrophage differentiation	-0.17	0.35	-9999	-0.78	80	80
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.068	0.17	-9999	-0.54	33	33
JUNB	-0.13	0.3	-9999	-0.74	41	41
FOS	-0.01	0.12	-9999	-0.76	13	13
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.034	0.15	-9999	-0.45	20	20
STAT1/PIAS1	-0.046	0.16	-9999	-0.49	19	19
GRB2/SOS1/GAB family/SHP2/PI3K	0.021	0.038	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.36	-9999	-0.82	80	80
PRKCD	-0.14	0.3	-9999	-0.69	63	63
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.033	0.12	-9999	-0.66	3	3
gp130 (dimer)/JAK1/JAK1/LMO4	-0.003	0.089	-9999	-0.47	16	16
Rac1/GTP	-0.18	0.23	-9999	-0.6	91	91
HCK	-0.033	0.2	-9999	-0.86	28	28
MAPKKK cascade	0.026	0.061	-9999	-10000	0	0
bone resorption	-0.18	0.35	-9999	-0.78	80	80
IRF1	-0.14	0.31	-9999	-0.75	42	42
mol:GDP	-0.15	0.26	-9999	-0.59	97	97
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.27	-9999	-0.6	97	97
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.003	0.12	-9999	-0.74	2	2
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.078	0.21	-9999	-0.63	63	63
gp130 (dimer)/TYK2/TYK2/LMO4	-0.013	0.084	-9999	-0.47	16	16
gp130 (dimer)/JAK2/JAK2/LMO4	-0.013	0.084	-9999	-0.47	16	16
IL6	-0.091	0.28	-9999	-0.82	63	63
PIAS3	0.016	0	-9999	-10000	0	0
PTPRE	0.017	0.017	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.015	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.034	0.13	-9999	-0.83	2	2
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.29	-9999	-0.75	80	80
MCL1	0.075	0.023	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.23	-9999	-0.48	168	168
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0.001	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.11	0.22	-9999	-0.52	6	6
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.01	0.13	-9999	-0.86	12	12
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.65	0.37	-9999	-0.86	386	386
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0.001	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.1	0.29	-9999	-0.86	66	66
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.17	0.24	-9999	-0.49	178	178
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.13	0.16	-9999	-0.59	16	16
MAP1B	-0.001	0.02	-9999	-0.33	2	2
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.17	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.75	167	167
PAFAH/LIS1	-0.44	0.24	-9999	-0.57	386	386
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.099	0.12	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.14	-9999	-0.7	1	1
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.13	0.19	-9999	-0.64	16	16
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.031	0	-9999	-10000	0	0
PAFAH1B3	0.014	0.034	-9999	-0.75	1	1
PAFAH1B2	0.014	0.034	-9999	-0.75	1	1
MAP1B/LIS1/Dynein heavy chain	-0.001	0.013	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.16	-9999	-0.56	16	16
LRP8	0.014	0.039	-9999	-0.86	1	1
NDEL1/Katanin 60	-0.13	0.16	-9999	-0.59	16	16
P39/CDK5	-0.18	0.23	-9999	-0.86	16	16
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.093	0.21	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.14	0.2	-9999	-0.63	3	3
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6
CDC42	0	0	-9999	-10000	0	0

×

EPO signaling pathway

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
BCL2L1	-0.02	0.18	-9999	-10000	0	0
CRKL	-0.094	0.22	-9999	-10000	0	0
mol:DAG	-0.12	0.17	-9999	-10000	0	0
HRAS	-0.11	0.15	-9999	-0.7	1	1
MAPK8	-0.13	0.25	-9999	-0.48	178	178
RAP1A	-0.094	0.22	-9999	-10000	0	0
GAB1	-0.094	0.22	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.48	178	178
EPO	-0.29	0.42	-9999	-0.85	178	178
PLCG1	-0.13	0.17	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.019	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.19	0.26	-9999	-0.55	179	179
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.31	-9999	-0.65	178	178
IRS2	-0.1	0.23	-9999	-0.88	2	2
STAT1	-0.065	0.21	-9999	-10000	0	0
STAT5B	-0.07	0.21	-9999	-10000	0	0
cell proliferation	-0.11	0.24	-9999	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.11	0.15	-9999	-0.71	1	1
TEC	-0.094	0.22	-9999	-10000	0	0
SOCS3	0.012	0.055	-9999	-0.86	2	2
STAT1 (dimer)	-0.063	0.21	-9999	-10000	0	0
JAK2	0.006	0.018	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
EPO/EPOR (dimer)/JAK2	-0.1	0.24	-9999	-10000	0	0
EPO/EPOR	-0.23	0.31	-9999	-0.65	178	178
LYN	0.018	0.001	-9999	-10000	0	0
TEC/VAV2	-0.081	0.22	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.019	-9999	-10000	0	0
SHC1	0.014	0.039	-9999	-0.86	1	1
EPO/EPOR (dimer)/LYN	-0.16	0.28	-9999	-0.54	178	178
mol:IP3	-0.12	0.17	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.13	0.18	-9999	-0.79	3	3
SH2B3	0.006	0.018	-9999	-10000	0	0
NFKB1	-0.14	0.26	-9999	-0.48	178	178
EPO/EPOR (dimer)/JAK2/SOCS3	-0.11	0.15	-9999	-0.53	1	1
PTPN6	-0.11	0.23	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.12	0.17	-9999	-10000	0	0
EPOR	0.007	0.019	-9999	-10000	0	0
INPP5D	0.009	0.078	-9999	-0.86	4	4
mol:GDP	-0.12	0.16	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
CRKL/CBL/C3G	-0.12	0.17	-9999	-0.73	1	1
VAV2	-0.094	0.22	-9999	-10000	0	0
CBL	-0.095	0.22	-9999	-0.8	1	1
SHC/Grb2/SOS1	-0.12	0.17	-9999	-10000	0	0
STAT5A	-0.07	0.21	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.045	0.21	-9999	-10000	0	0
LYN/PLCgamma2	-0.01	0.078	-9999	-0.62	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.28	-9999	-0.88	26	26
BCL2	-0.02	0.18	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.24	0.28	-9999	-0.85	72	72
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.015	0.09	-9999	-0.57	13	13
IFNAR2	0.015	0.007	-9999	-10000	0	0
AKT1	0.014	0.07	-9999	-0.43	10	10
ER alpha/Oestrogen	-0.005	0.053	-9999	-0.6	4	4
NFX1/SIN3/HDAC complex	0.045	0.054	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.75	455	455
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.22	0.26	-9999	-0.8	70	70
SAP18	0.013	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.34	0.38	-9999	-0.75	238	238
WRN	0.016	0	-9999	-10000	0	0
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.18	0.23	-9999	-0.75	47	47
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.24	0.29	-9999	-0.89	70	70
CCND1	-0.22	0.27	-9999	-0.8	75	75
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.013	0.006	-9999	-10000	0	0
RBBP4	0.012	0.034	-9999	-0.75	1	1
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.013	0.006	-9999	-10000	0	0
Telomerase/911	0.003	0.027	-9999	-10000	0	0
CDKN1B	-0.22	0.3	-9999	-0.55	230	230
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	-0.018	0.16	-9999	-0.86	18	18
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.014	0.006	-9999	-10000	0	0
E6	-0.001	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.006	0.12	-9999	-0.76	13	13
IFN-gamma/IRF1	-0.29	0.32	-9999	-0.65	230	230
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.003	0.13	-9999	-0.86	11	11
Telomerase	-0.02	0.16	-9999	-0.47	8	8
IRF1	0.016	0.04	-9999	-0.86	1	1
ESR1	0.007	0.07	-9999	-0.78	4	4
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.022	-9999	-0.49	1	1
ubiquitin-dependent protein catabolic process	0.051	0.051	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.007	0.033	-9999	-10000	0	0
HDAC1	0.013	0.006	-9999	-10000	0	0
HDAC2	0.015	0.007	-9999	-10000	0	0
ATM	-0.001	0.023	-9999	-0.52	1	1
SMAD3	0.025	0.068	-9999	-0.66	5	5
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.006	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.17	0.25	-9999	-0.76	62	62
NR2F2	0.009	0.012	-9999	-10000	0	0
MAPK3	0.009	0.097	-9999	-0.67	10	10
MAPK1	0.009	0.097	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.007	0.086	-9999	-0.86	5	5
NFKB1	0.014	0.034	-9999	-0.75	1	1
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.023	-9999	-0.52	1	1
NBN	0.016	0	-9999	-10000	0	0
EGFR	0	0.11	-9999	-0.85	9	9
mol:Oestrogen	0	0.002	-9999	-10000	0	0
EGF/EGFR	-0.52	0.18	-9999	-0.57	456	456
MYC	-0.017	0.16	-9999	-0.86	18	18
IL2	-0.008	0.12	-9999	-0.86	10	10
KU	0	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.007	0.087	-9999	-0.86	5	5
TRF2/BLM	-0.013	0.091	-9999	-0.62	11	11
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.21	0.26	-9999	-0.81	63	63
SP1/HDAC2	0.007	0.014	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.18	0.23	-9999	-0.75	47	47
Smad3/Myc	-0.019	0.13	-9999	-0.6	22	22
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.85	230	230
Telomerase/PinX1	-0.18	0.23	-9999	-0.75	47	47
Telomerase/AKT1/mTOR/p70S6K	-0.012	0.079	-9999	-0.53	2	2
SIN3B	0.013	0.006	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.18	0.23	-9999	-0.75	47	47
response to DNA damage stimulus	0.004	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.18	0.23	-9999	-0.75	47	47
E2F1	-0.091	0.29	-9999	-0.86	61	61
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.14	0.33	-9999	-0.86	88	88
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.17	0.26	-10000	0	-0.53	87	87
CRKL	0.018	0.11	-10000	0	-0.45	20	20
HRAS	-0.042	0.18	-10000	0	-0.51	38	38
mol:PIP3	-0.003	0.11	-10000	0	-0.44	20	20
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.014	0.034	-10000	0	-0.75	1	1
GAB1	0.007	0.12	-10000	0	-0.49	20	20
FOXO3	0.025	0.1	-10000	0	-0.59	4	4
AKT1	0.014	0.11	-10000	0	-0.45	20	20
BAD	0.023	0.11	-10000	0	-0.59	5	5
megakaryocyte differentiation	-0.069	0.21	-10000	0	-0.45	107	107
GSK3B	0.025	0.1	-10000	0	-0.59	4	4
RAF1	-0.01	0.15	-10000	0	-0.45	9	9
SHC1	0.014	0.039	-10000	0	-0.86	1	1
STAT3	0.007	0.12	-10000	0	-0.49	20	20
STAT1	-0.015	0.24	-10000	0	-1	20	20
HRAS/SPRED1	-0.067	0.12	-10000	0	-0.43	17	17
cell proliferation	0.008	0.12	-10000	0	-0.48	20	20
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.008	0.12	-10000	0	-0.47	22	22
HRAS/SPRED2	-0.067	0.12	-10000	0	-0.43	18	18
LYN/TEC/p62DOK	-0.017	0.099	-10000	0	-0.66	4	4
MAPK3	0.012	0.11	-10000	0	-0.37	2	2
STAP1	-0.31	0.22	-10000	0	-0.42	382	382
GRAP2	-0.043	0.22	-10000	0	-0.86	34	34
JAK2	-0.066	0.18	-10000	0	-0.79	27	27
STAT1 (dimer)	-0.013	0.23	-10000	0	-1	20	20
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.12	0.21	-10000	0	-0.46	125	125
actin filament polymerization	0.003	0.12	-10000	0	-0.47	25	25
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.29	0.23	-10000	0	-0.86	29	29
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
CBL/CRKL/GRB2	-0.014	0.091	-10000	0	-0.59	4	4
PI3K	-0.019	0.1	-10000	0	-0.45	21	21
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.34	-10000	0	-1.3	22	22
MAPK8	0.007	0.12	-10000	0	-0.49	20	20
STAT3 (dimer)	0.008	0.12	-10000	0	-0.48	20	20
positive regulation of transcription	0.015	0.098	-10000	0	-0.31	1	1
mol:GDP	-0.11	0.19	-10000	0	-0.62	41	41
PIK3C2B	0.007	0.12	-10000	0	-0.49	20	20
CBL/CRKL	0.026	0.11	-10000	0	-0.62	4	4
FER	0.006	0.12	-10000	0	-0.5	22	22
SH2B3	0.007	0.12	-10000	0	-0.49	20	20
PDPK1	0.007	0.1	-10000	0	-0.56	5	5
SNAI2	0.007	0.12	-10000	0	-0.51	20	20
positive regulation of cell proliferation	0.001	0.18	-10000	0	-0.69	27	27
KITLG	0.001	0.1	-10000	0	-0.77	9	9
cell motility	0.001	0.18	-10000	0	-0.69	27	27
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.04	0.071	-10000	0	-10000	0	0
STAT5A (dimer)	0.004	0.16	-10000	0	-0.58	28	28
SOCS1	0.005	0.095	-10000	0	-0.86	6	6
cell migration	0.04	0.19	0.5	64	-10000	0	64
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.29	0.42	-10000	0	-0.85	178	178
VAV1	-0.19	0.37	-10000	0	-0.86	119	119
GRB10	0.007	0.12	-10000	0	-0.49	20	20
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.034	0.11	-10000	0	-0.45	32	32
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.006	0.12	-10000	0	-0.42	2	2
CBL	0.014	0.034	-10000	0	-0.75	1	1
KIT	-0.009	0.28	-10000	0	-1.1	27	27
MAP2K2	0.005	0.12	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.018	0.1	-10000	0	-0.61	5	5
STAT5A	0.003	0.16	-10000	0	-0.6	28	28
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.007	0.12	-10000	0	-0.49	20	20
SHC/GRAP2	-0.046	0.17	-10000	0	-0.66	35	35
PTPRO	-0.071	0.22	-10000	0	-0.46	107	107
SH2B2	0.002	0.13	-10000	0	-0.48	25	25
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.042	0.19	-10000	0	-0.51	64	64
CREBBP	0.045	0.012	-10000	0	-10000	0	0
BCL2	0.043	0.068	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.019	0.11	-10000	0	-1.4	1	1
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.018	0	-10000	0	-10000	0	0
TBX21	-0.24	0.41	-10000	0	-0.82	161	161
SUMO2	0.011	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.025	0.054	-10000	0	-1.2	1	1
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	0.004	0.1	-10000	0	-0.84	7	7
GR alpha/HSP90/FKBP51/HSP90	0.053	0.13	0.39	4	-0.58	7	11
PRL	-0.014	0.11	-10000	0	-0.56	1	1
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.57	75	-0.62	2	77
RELA	0.004	0.076	-10000	0	-10000	0	0
FGG	-0.14	0.43	0.59	11	-0.72	150	161
GR beta/TIF2	0.052	0.14	0.42	5	-0.54	8	13
IFNG	-0.41	0.43	-10000	0	-0.86	207	207
apoptosis	-0.094	0.21	-10000	0	-0.8	2	2
CREB1	-0.015	0.1	-10000	0	-0.42	1	1
histone acetylation	0.016	0.13	0.38	7	-0.5	4	11
BGLAP	-0.008	0.13	-10000	0	-0.74	3	3
GR/PKAc	0.064	0.1	0.4	2	-0.6	1	3
NF kappa B1 p50/RelA	0.011	0.15	-10000	0	-0.58	7	7
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.046	0.093	0.33	7	-10000	0	7
GATA3	-0.35	0.38	-10000	0	-0.74	244	244
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.029	0.15	-10000	0	-0.74	12	12
GSK3B	0.011	0.007	-10000	0	-10000	0	0
NR1I3	-0.058	0.23	-10000	0	-0.83	12	12
CSN2	0.044	0.19	0.5	4	-0.66	1	5
BRG1/BAF155/BAF170/BAF60A	0.003	0.013	-10000	0	-10000	0	0
NFATC1	0.018	0.005	-10000	0	-10000	0	0
POU2F1	0.02	0.005	-10000	0	-10000	0	0
CDKN1A	0.05	0.053	-10000	0	-0.72	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.086	0.28	-10000	0	-0.83	61	61
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.007	0.21	0.39	1	-0.6	20	21
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.058	0.22	-10000	0	-0.84	12	12
JUN	-0.21	0.24	-10000	0	-0.61	81	81
IL4	-0.022	0.12	-10000	0	-0.63	1	1
CDK5R1	0.012	0.007	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.26	0.3	4	-0.64	101	105
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.059	0.12	0.41	2	-0.6	4	6
cortisol/GR alpha (monomer)	0.15	0.34	0.67	85	-0.8	1	86
NCOA2	0.004	0.095	-10000	0	-0.75	8	8
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.055	0.14	-10000	0	-0.83	13	13
AP-1/NFAT1-c-4	-0.32	0.34	-10000	0	-0.81	103	103
AFP	-0.35	0.56	-10000	0	-1.4	106	106
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.083	0.15	0.54	5	-0.62	1	6
TP53	0.044	0.021	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.25	0.41	-10000	0	-1.2	66	66
KRT14	-0.14	0.29	-10000	0	-0.83	69	69
TBP	0.028	0.01	-10000	0	-10000	0	0
CREBBP	0.045	0.078	-10000	0	-10000	0	0
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.011	0.014	-10000	0	-10000	0	0
AP-1	-0.32	0.34	-10000	0	-0.82	105	105
MAPK14	0.011	0.007	-10000	0	-10000	0	0
MAPK10	0.004	0.076	-10000	0	-0.76	5	5
MAPK11	0.009	0.04	-10000	0	-0.88	1	1
KRT5	-0.26	0.38	-10000	0	-0.93	100	100
interleukin-1 receptor activity	0.001	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.055	-10000	0	-1.2	1	1
CGA	-0.13	0.37	-10000	0	-1.2	50	50
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.087	0.15	0.49	25	-10000	0	25
MAPK3	0.011	0.007	-10000	0	-10000	0	0
MAPK1	0.011	0.007	-10000	0	-10000	0	0
ICAM1	-0.048	0.23	-10000	0	-0.75	28	28
NFKB1	0.003	0.086	-10000	0	-0.9	1	1
MAPK8	-0.14	0.19	-10000	0	-0.52	36	36
MAPK9	0.011	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.1	0.22	-10000	0	-0.86	2	2
BAX	0.052	0.029	-10000	0	-10000	0	0
POMC	-0.036	0.17	-10000	0	-0.86	6	6
EP300	0.043	0.083	-10000	0	-0.6	1	1
cortisol/GR alpha (dimer)/p53	0.16	0.28	0.59	82	-0.7	1	83
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.071	0.29	1	-10000	0	1
SGK1	0.1	0.095	-10000	0	-10000	0	0
IL13	-0.35	0.28	-10000	0	-0.77	103	103
IL6	-0.12	0.38	-10000	0	-0.98	69	69
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.29	0.21	-10000	0	-0.73	32	32
IL2	-0.17	0.25	-10000	0	-0.76	37	37
CDK5	0.012	0.007	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.077	0.3	-10000	0	-0.92	42	42
CDK5R1/CDK5	0	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.027	0.11	-10000	0	-0.63	1	1
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.58	58	-0.65	1	59
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.15	0.42	27	-10000	0	27
NF kappa B1 p50/RelA/Cbp	0.06	0.14	-10000	0	-0.94	1	1
JUN (dimer)	-0.21	0.24	-10000	0	-0.61	81	81
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.058	0.22	-10000	0	-0.92	19	19
NR3C1	0.079	0.19	0.5	31	-0.94	1	32
NR4A1	0.001	0.13	-10000	0	-0.73	16	16
TIF2/SUV420H1	-0.009	0.07	-10000	0	-0.56	8	8
MAPKKK cascade	-0.094	0.21	-10000	0	-0.8	2	2
cortisol/GR alpha (dimer)/Src-1	0.15	0.28	0.58	81	-0.8	1	82
PBX1	-0.003	0.13	-10000	0	-0.74	15	15
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.096	0.37	-10000	0	-1.3	38	38
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.15	0.42	27	-10000	0	27
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.58	58	-0.65	1	59
mol:cortisol	0.062	0.19	0.41	61	-10000	0	61
MMP1	-0.23	0.4	-10000	0	-0.98	99	99

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	225	225
alphaV beta3 Integrin	-0.008	0.067	-9999	-0.55	7	7
PTK2	-0.14	0.23	-9999	-0.55	46	46
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.014	0.039	-9999	-0.86	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.084	0.19	-9999	-0.53	78	78
VEGFA	-0.37	0.44	-9999	-0.86	225	225
ILK	-0.084	0.19	-9999	-0.53	78	78
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.077	0.18	-9999	-0.5	70	70
PTK2B	-0.19	0.27	-9999	-0.88	1	1
alphaV/beta3 Integrin/JAM-A	-0.069	0.15	-9999	-0.52	10	10
CBL	0.014	0.034	-9999	-0.75	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.48	235	235
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.065	-9999	-0.52	6	6
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.14	-9999	-0.47	43	43
alphaV/beta3 Integrin/Syndecan-1	-0.008	0.063	-9999	-0.48	9	9
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-9999	-0.82	3	3
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
alphaV/beta3 Integrin/Osteopontin	-0.007	0.056	-9999	-0.48	7	7
RPS6KB1	-0.042	0.13	-9999	-0.75	3	3
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.041	0.093	-9999	-0.69	4	4
GPR124	0.012	0.055	-9999	-0.86	2	2
MAPK1	-0.041	0.093	-9999	-0.69	4	4
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
alphaV/beta3 Integrin/Tumstatin	-0.057	0.16	-9999	-0.48	60	60
cell adhesion	-0.17	0.18	-9999	-0.83	1	1
ANGPTL3	-0.33	0.38	-9999	-0.75	232	232
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	225	225
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.011	0.059	-9999	-0.75	3	3
IGF1	0.005	0.095	-9999	-0.86	6	6
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.005	0.051	-9999	-0.51	5	5
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.003	0.037	-9999	-0.48	3	3
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.016	0.093	-9999	-0.54	15	15
CSF1	0.014	0.034	-9999	-0.75	1	1
PIK3C2A	-0.086	0.2	-9999	-0.54	79	79
PI4 Kinase/Pyk2	-0.23	0.24	-9999	-0.76	44	44
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	225	225
FAK1/Vinculin	-0.11	0.18	-9999	-0.56	3	3
alphaV beta3/Integrin/ppsTEM5	-0.005	0.051	-9999	-0.52	5	5
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.1	0.28	-9999	-0.76	78	78
BCAR1	0.014	0.034	-9999	-0.75	1	1
FGF2	0.008	0.078	-9999	-0.77	5	5
F11R	0.025	0.061	-9999	-0.58	5	5
alphaV/beta3 Integrin/Lactadherin	-0.004	0.045	-9999	-0.5	4	4
alphaV/beta3 Integrin/TGFBR2	-0.003	0.037	-9999	-0.48	3	3
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.042	-9999	-0.86	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.003	0.034	-9999	-0.44	3	3
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.05	0.23	-9999	-0.86	38	38
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.88	1	1
SDC1	0.007	0.083	-9999	-0.75	6	6
VAV3	0.039	0.085	-9999	-0.8	1	1
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.011	0.059	-9999	-0.75	3	3
FAK1/Paxillin	-0.11	0.18	-9999	-0.56	3	3
cell migration	-0.088	0.17	-9999	-0.52	2	2
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.062	0.14	-9999	-1.1	1	1
SPP1	0.01	0.068	-9999	-0.75	4	4
KDR	0.014	0.034	-9999	-0.75	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	-0.072	0.24	-9999	-0.75	58	58
angiogenesis	0.004	0.15	-9999	-0.67	4	4
Rac1/GTP	-0.012	0.068	-9999	-0.73	1	1
EDIL3	-0.005	0.13	-9999	-0.79	13	13
cell proliferation	-0.003	0.036	-9999	-0.48	3	3

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.045	-9999	-10000	0	0
BIRC5	-0.25	0.4	-9999	-0.86	151	151
NFKBIA	0.047	0.04	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.76	99	99
AKT1	0.047	0.04	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.018	0.041	-9999	-10000	0	0
NDEL1/TACC3	0.016	0.076	-9999	-0.74	4	4
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.014	0.019	-9999	-10000	0	0
PAK1/Aurora A	0.02	0.045	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.011	0.059	-9999	-0.75	3	3
TPX2	-0.14	0.3	-9999	-0.67	125	125
TP53	0.025	0.037	-9999	-10000	0	0
DLG7	0.02	0.044	-9999	-0.29	6	6
AURKAIP1	0.011	0.062	-9999	-0.79	3	3
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.017	0.08	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.017	0.041	-9999	-10000	0	0
AURKA	0.027	0.055	-9999	-0.34	6	6
AURKB	-0.14	0.15	-9999	-0.29	240	240
CDC25B	0.018	0.063	-9999	-0.58	2	2
G2/M transition checkpoint	0.015	0.054	-9999	-0.44	3	3
mRNA polyadenylation	-0.072	0.19	-9999	-0.44	99	99
Aurora A/CPEB	-0.072	0.19	-9999	-0.45	99	99
Aurora A/TACC1/TRAP/chTOG	0.022	0.044	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.02	0.045	-9999	-10000	0	0
regulation of centrosome cycle	-0.007	0.066	-9999	-0.73	4	4
spindle assembly	-0.003	0.023	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.14	0.22	-9999	-0.47	151	151
CENPA	-0.12	0.14	-9999	-0.3	167	167
Aurora A/PP2A	0.02	0.045	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.053	0.036	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.037	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0.034	-9999	-0.75	1	1
Ajuba/Aurora A	0.015	0.054	-9999	-0.44	3	3
mitotic prometaphase	0.037	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.05	-9999	-0.34	6	6
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.009	0.078	-9999	-0.86	4	4
Aurora A/Antizyme1	0.018	0.062	-9999	-0.52	2	2
Aurora A/RasGAP	0.019	0.051	-9999	-0.48	1	1
OAZ1	0.014	0.039	-9999	-0.86	1	1
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.014	0.019	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.3	-9999	-0.66	125	125
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.09	0.25	-9999	-0.52	125	125
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	0	-9999	-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	-0.087	0.31	-10000	0	-0.91	29	29
NCK1/PAK1/Dok-R	-0.084	0.11	-10000	0	-0.41	33	33
NCK1/Dok-R	-0.086	0.27	-10000	0	-1.1	31	31
PIK3CA	0.004	0.034	-10000	0	-0.75	1	1
mol:beta2-estradiol	-0.006	0.039	0.32	5	-10000	0	5
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.006	0.04	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.32	0.42	-10000	0	-0.85	191	191
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.059	0.24	-10000	0	-0.97	30	30
FN1	-0.05	0.23	-10000	0	-0.86	38	38
PLD2	0.031	0.3	-10000	0	-1.1	30	30
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.027	0.17	-10000	0	-0.75	28	28
ELK1	0.06	0.27	-10000	0	-0.97	30	30
GRB7	0.005	0.089	-10000	0	-0.75	7	7
PAK1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.3	-10000	0	-1	44	44
CDKN1A	-0.11	0.31	-10000	0	-0.66	24	24
ITGA5	-0.048	0.23	-10000	0	-0.86	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.086	0.27	-10000	0	-1.1	31	31
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.051	0.26	-10000	0	-0.65	29	29
PLG	-0.19	0.35	-10000	0	-1.3	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.21	-10000	0	-0.85	29	29
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.035	-10000	0	-0.75	1	1
ANGPT2	-0.21	0.38	-10000	0	-0.64	165	165
BMX	-0.038	0.34	-10000	0	-1.1	30	30
ANGPT1	0.074	0.2	-10000	0	-1.2	8	8
tube development	-0.13	0.34	-10000	0	-0.73	25	25
ANGPT4	-0.018	0.15	-10000	0	-0.87	15	15
response to hypoxia	-0.003	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.046	0.32	-10000	0	-1.2	30	30
alpha5/beta1 Integrin	-0.049	0.17	-10000	0	-0.66	37	37
FGF2	0.009	0.08	-10000	0	-0.77	5	5
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	25	25
mol:L-citrulline	-0.051	0.26	-10000	0	-0.65	29	29
AGTR1	-0.037	0.17	-10000	0	-0.75	28	28
MAPK14	-0.006	0.31	-10000	0	-1.2	29	29
Tie2/SHP2	-0.063	0.26	-10000	0	-1.1	28	28
TEK	-0.049	0.29	-10000	0	-1.2	28	28
RPS6KB1	-0.049	0.28	-10000	0	-0.87	29	29
Angiotensin II/AT1	-0.044	0.13	-10000	0	-0.58	28	28
Tie2/Ang1/GRB2	-0.025	0.3	-10000	0	-1.1	30	30
MAPK3	0.043	0.28	-10000	0	-1	30	30
MAPK1	0.043	0.28	-10000	0	-1	30	30
Tie2/Ang1/GRB7	-0.03	0.31	-10000	0	-1.2	30	30
NFKB1	0.014	0.034	-10000	0	-0.75	1	1
MAPK8	0.03	0.3	-10000	0	-1.1	30	30
PI3K	-0.073	0.32	-10000	0	-1.1	29	29
FES	-0.011	0.32	-10000	0	-1.1	30	30
Crk/Dok-R	-0.085	0.27	-10000	0	-1.1	30	30
Tie2/Ang1/ABIN2	-0.025	0.3	-10000	0	-1.1	30	30
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.076	0.29	-10000	0	-0.8	29	29
STAT5A	0.016	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.049	0.28	-10000	0	-0.87	29	29
Tie2/Ang2	-0.19	0.41	-10000	0	-0.99	31	31
Tie2/Ang1	0.022	0.33	-10000	0	-1.2	30	30
FOXO1	-0.11	0.31	-10000	0	-0.81	29	29
ELF1	0.023	0.036	-10000	0	-0.73	1	1
ELF2	0.026	0.31	-10000	0	-1.1	30	30
mol:Choline	0.034	0.29	-10000	0	-1	30	30
cell migration	-0.056	0.071	-10000	0	-10000	0	0
FYN	-0.16	0.36	-10000	0	-0.85	25	25
DOK2	-0.038	0.21	-10000	0	-0.86	31	31
negative regulation of cell cycle	-0.098	0.3	-10000	0	-0.6	24	24
ETS1	0.028	0.038	-10000	0	-10000	0	0
PXN	-0.027	0.25	-10000	0	-0.7	29	29
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.062	0.28	-10000	0	-0.75	29	29
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.008	0.11	-10000	0	-0.79	8	8
MAPKKK cascade	0.034	0.29	-10000	0	-1	30	30
RASA1	0.014	0.034	-10000	0	-0.75	1	1
Tie2/Ang1/Shc	-0.005	0.31	-10000	0	-1.1	30	30
NCK1	0.014	0.034	-10000	0	-0.75	1	1
vasculogenesis	-0.042	0.24	-10000	0	-0.58	29	29
mol:Phosphatidic acid	0.034	0.29	-10000	0	-1	30	30
mol:Angiotensin II	-0.017	0.022	-10000	0	-10000	0	0
mol:NADP	-0.051	0.26	-10000	0	-0.65	29	29
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	29	29
MMP2	0.025	0.31	-10000	0	-1.1	30	30

×

Visual signal transduction: Rods

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
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.009	0.079	-9999	-0.68	7	7
Metarhodopsin II/Arrestin	-0.019	0.1	-9999	-0.59	16	16
PDE6G/GNAT1/GTP	-0.013	0.085	-9999	-0.56	12	12
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.006	0.1	-9999	-0.86	7	7
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.11	0.21	-9999	-0.95	12	12
mol:Na +	-0.11	0.21	-9999	-0.81	19	19
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	35	35
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.11	0.22	-9999	-0.85	19	19
CNGB1	-0.009	0.13	-9999	-0.86	11	11
RDH5	-0.003	0.12	-9999	-0.83	11	11
SAG	0.001	0.039	-9999	-0.86	1	1
mol:Ca2+	-0.067	0.22	-9999	-0.78	19	19
Na + (4 Units)	-0.1	0.19	-9999	-0.74	19	19
RGS9	-0.007	0.14	-9999	-0.81	14	14
GNB1/GNGT1	-0.23	0.32	-9999	-0.66	172	172
GNAT1/GDP	-0.037	0.13	-9999	-0.53	14	14
GUCY2D	-0.028	0.18	-9999	-0.86	23	23
GNGT1	-0.28	0.41	-9999	-0.86	172	172
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.038	0.15	-9999	-0.6	27	27
mol:11-cis-retinal	-0.003	0.12	-9999	-0.83	11	11
mol:cGMP	-0.039	0.14	-9999	-0.52	36	36
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.034	0.14	-9999	-0.65	26	26
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.12	0.3	-9999	-0.75	93	93
Metarhodopsin II	-0.016	0.093	-9999	-0.55	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.041	0.14	-9999	-0.54	38	38
RGS9BP	-0.016	0.15	-9999	-0.75	21	21
Metarhodopsin II/Transducin	-0.11	0.16	-9999	-0.62	11	11
GCAP Family/Ca ++	-0.017	0.098	-9999	-0.56	15	15
PDE6A/B	-0.035	0.15	-9999	-0.66	27	27
mol:Pi	-0.034	0.13	-9999	-0.5	35	35
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.27	-9999	-0.55	174	174
PDE6B	0.007	0.083	-9999	-0.75	6	6
PDE6A	-0.024	0.18	-9999	-0.86	22	22
PDE6G	0.008	0.078	-9999	-0.77	5	5
RHO	-0.016	0.15	-9999	-0.86	15	15
PDE6	-0.056	0.16	-9999	-0.83	8	8
GUCA1A	-0.009	0.12	-9999	-0.86	9	9
GC2/GCAP Family	-0.017	0.098	-9999	-0.56	15	15
GUCA1C	0.001	0.048	-9999	-0.75	2	2
GUCA1B	0.007	0.087	-9999	-0.86	5	5

×

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	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.047	0.1	-10000	0	-0.47	9	9
PTP1B/AKT1	-0.032	0.047	-10000	0	-0.41	2	2
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.049	0.053	-10000	0	-0.39	5	5
EGFR	-0.014	0.12	-10000	0	-0.87	9	9
EGF/EGFR	-0.37	0.14	-10000	0	-0.41	454	454
CSF1	0.014	0.034	-10000	0	-0.75	1	1
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.048	0.086	-10000	0	-0.44	17	17
Insulin Receptor/Insulin	-0.008	0.034	-10000	0	-10000	0	0
HCK	-0.033	0.2	-10000	0	-0.86	28	28
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.035	0.05	-10000	0	-0.44	2	2
EGF	-0.67	0.23	-10000	0	-0.75	455	455
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	39	39
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.032	0.051	-10000	0	-0.43	5	5
cell migration	0.049	0.053	0.39	5	-10000	0	5
STAT3	0.015	0.001	-10000	0	-10000	0	0
PRLR	-0.093	0.25	-10000	0	-0.75	64	64
ITGA2B	-0.029	0.16	-10000	0	-0.86	18	18
CSF1R	0.004	0.1	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.072	0.19	-10000	0	-0.57	64	64
FGR	0.011	0.067	-10000	0	-0.86	3	3
PTP1B/p130 Cas	-0.036	0.052	-10000	0	-0.41	4	4
Crk/p130 Cas	-0.031	0.042	-10000	0	-0.42	2	2
DOK1	-0.019	0.046	-10000	0	-0.38	2	2
JAK2	-0.053	0.11	-10000	0	-0.38	23	23
Jak2/Leptin Receptor/Leptin	-0.053	0.13	-10000	0	-0.52	9	9
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
PTPN1	-0.049	0.053	-10000	0	-0.39	5	5
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.007	0.13	-10000	0	-0.75	15	15
SRC	0	0.021	-10000	0	-10000	0	0
ITGB3	-0.003	0.058	-10000	0	-0.75	3	3
CAT1/PTP1B	-0.24	0.14	-10000	0	-0.56	40	40
CAPN1	0.002	0.005	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0.009	0.043	-10000	0	-0.63	1	1
mol:H2O2	-0.007	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.035	0.12	-10000	0	-0.6	3	3
negative regulation of transcription	-0.052	0.11	-10000	0	-0.38	23	23
FCGR2A	-0.024	0.18	-10000	0	-0.86	23	23
FER	-0.001	0.048	-10000	0	-0.76	2	2
alphaIIb/beta3 Integrin	-0.027	0.13	-10000	0	-0.65	21	21
BLK	-0.04	0.21	-10000	0	-0.86	32	32
Insulin Receptor/Insulin/Shc	-0.001	0.026	-10000	0	-0.59	1	1
RHOA	0.002	0.005	-10000	0	-10000	0	0
LEPR	0.014	0.004	-10000	0	-10000	0	0
BCAR1	0.014	0.034	-10000	0	-0.75	1	1
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.22	0.15	-10000	0	-0.55	59	59
PRL	0.001	0.004	-10000	0	-10000	0	0
SOCS3	0.028	0.049	-10000	0	-0.72	2	2
SPRY2	0.001	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.038	-10000	0	-0.49	3	3
CSF1/CSF1R	-0.038	0.076	-10000	0	-0.53	10	10
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.011	0.059	-10000	0	-0.75	3	3
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.075	0.26	-10000	0	-0.86	50	50
STAT5B	-0.045	0.068	-10000	0	-0.46	5	5
STAT5A	-0.045	0.068	-10000	0	-0.46	5	5
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.035	0.05	-10000	0	-0.42	3	3
CSN2	-0.007	0.068	-10000	0	-10000	0	0
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
LAT	-0.1	0.17	-10000	0	-0.35	146	146
YBX1	0.003	0.008	-10000	0	-10000	0	0
LCK	-0.022	0.18	-10000	0	-0.85	22	22
SHC1	0.014	0.039	-10000	0	-0.86	1	1
NOX4	-0.006	0.075	-10000	0	-0.76	5	5

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.012	0.055	-9999	-0.86	2	2
RELN/VLDLR/Fyn	-0.16	0.23	-9999	-0.48	167	167
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.002	0.04	-9999	-0.81	1	1
AKT1	-0.067	0.16	-9999	-0.57	2	2
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.01	0.13	-9999	-0.86	12	12
RELN/LRP8/DAB1	-0.16	0.22	-9999	-0.46	179	179
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.52	18	18
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.82	1	1
long-term memory	-0.21	0.25	-9999	-0.88	24	24
DAB1/LIS1	-0.14	0.18	-9999	-0.86	1	1
DAB1/CRLK/C3G	-0.13	0.18	-9999	-0.82	1	1
PIK3CA	0.014	0.034	-9999	-0.75	1	1
DAB1/NCK2	-0.14	0.19	-9999	-0.86	1	1
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.11	0.3	-9999	-0.83	75	75
CDK5R1	0.016	0.001	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.75	167	167
PIK3R1	0.014	0.034	-9999	-0.75	1	1
RELN/LRP8/Fyn	-0.16	0.23	-9999	-0.48	168	168
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.26	-9999	-0.9	24	24
MAPK8	0.016	0.001	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.45	178	178
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.88	2	2
RELN/LRP8	-0.16	0.23	-9999	-0.48	168	168
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.9	2	2
PI3K	-0.002	0.035	-9999	-0.56	2	2
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.042	-9999	-0.66	2	2
RAP1A	-0.11	0.17	-9999	-0.75	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.048	-9999	-0.75	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.008	0.055	-9999	-0.86	2	2
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.028	0.12	-9999	-0.54	2	2
neuron adhesion	-0.05	0.19	-9999	-0.71	1	1
LRP8	0.014	0.039	-9999	-0.86	1	1
GSK3B	-0.053	0.15	-9999	-0.54	2	2
RELN/VLDLR/DAB1/Fyn	-0.15	0.2	-9999	-0.52	17	17
MAP3K11	0.014	0.034	-9999	-0.75	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.15	-9999	-0.61	2	2
CDK5	0.016	0	-9999	-10000	0	0
MAPT	0.015	0.084	-9999	-0.69	6	6
neuron migration	-0.059	0.21	-9999	-0.61	1	1
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.057	0.1	-9999	-0.54	2	2
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6

×

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

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
BAG4	0.014	0.034	-9999	-0.75	1	1
Caspase 8 (4 units)	-0.097	0.092	-9999	-10000	0	0
NEF	-0.058	0.084	-9999	-10000	0	0
NFKBIA	0.001	0.045	-9999	-10000	0	0
BIRC3	-0.071	0.31	-9999	-0.79	78	78
CYCS	-0.078	0.14	-9999	-0.43	1	1
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.37	0.48	-9999	-1	165	165
MAP2K7	-0.041	0.11	-9999	-10000	0	0
protein ubiquitination	0.06	0.071	-9999	-0.42	3	3
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.016	0	-9999	-10000	0	0
BID	-0.091	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.051	0.12	-9999	-0.46	1	1
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.051	0.12	-9999	-0.46	1	1
MAPK8	-0.028	0.1	-9999	-10000	0	0
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.014	0.039	-9999	-0.86	1	1
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.13	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.047	0.067	-9999	-10000	0	0
CHUK	0.061	0.075	-9999	-0.46	3	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.4	0.44	-9999	-0.74	271	271
TNF	0.003	0.1	-9999	-0.8	8	8
FASLG	-0.57	0.61	-9999	-1.1	271	271
NFKB1	0	0.055	-9999	-0.74	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.069	-9999	-0.52	9	9
CASP6	-0.048	0.052	-9999	-10000	0	0
CASP7	-0.061	0.21	-9999	-0.55	52	52
RELA	0.001	0.045	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.061	0.21	-9999	-0.55	52	52
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.025	-9999	-0.56	1	1
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.053	0.08	-9999	-0.53	3	3
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.56	52	52
BCL2	-0.016	0.096	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.043	0.15	-9999	-0.58	38	38
EPHB2	0	0.11	-9999	-0.77	10	10
Syndecan-2/TACI	-0.056	0.17	-9999	-0.58	49	49
LAMA1	-0.007	0.13	-9999	-0.76	15	15
Syndecan-2/alpha2 ITGB1	-0.01	0.067	-9999	-0.49	7	7
HRAS	0.014	0.039	-9999	-0.86	1	1
Syndecan-2/CASK	0	0	-9999	-10000	0	0
ITGA5	-0.048	0.23	-9999	-0.86	37	37
BAX	0.055	0.001	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
LAMA3	0.004	0.1	-9999	-0.86	7	7
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.002	0.11	-9999	-0.86	8	8
Syndecan-2/MMP2	-0.007	0.061	-9999	-0.56	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.004	0.05	-9999	-0.56	4	4
dendrite morphogenesis	-0.01	0.069	-9999	-0.5	10	10
Syndecan-2/GM-CSF	-0.017	0.098	-9999	-0.58	15	15
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.026	-9999	-0.58	1	1
GNB2L1	0.014	0.039	-9999	-0.86	1	1
MAPK3	0.021	0.095	-9999	-0.52	15	15
MAPK1	0.021	0.095	-9999	-0.52	15	15
Syndecan-2/RACK1	-0.002	0.031	-9999	-0.5	2	2
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.027	0	-9999	-10000	0	0
ITGA2	0.01	0.068	-9999	-0.75	4	4
MAPK8	0.047	0.001	-9999	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	-0.015	0.081	-9999	-0.65	2	2
Syndecan-2/Kininogen	-0.36	0.21	-9999	-0.48	379	379
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.048	0.032	-9999	-0.46	2	2
Syndecan-2/CASK/Protein 4.1	0	0	-9999	-10000	0	0
extracellular matrix organization	-0.006	0.057	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.043	0.15	-9999	-0.57	38	38
Syndecan-2/Caveolin-2/Ras	-0.009	0.069	-9999	-0.52	9	9
Syndecan-2/Laminin alpha3	-0.008	0.067	-9999	-0.58	7	7
Syndecan-2/RasGAP	-0.003	0.044	-9999	-0.67	2	2
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.66	37	37
PRKCD	0.014	0.039	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.07	-9999	-0.5	10	10
GO:0007205	0.005	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.003	0.042	-9999	-0.83	1	1
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.071	0.26	-9999	-0.86	49	49
RASA1	0.014	0.034	-9999	-0.75	1	1
alpha2/beta1 Integrin	-0.004	0.05	-9999	-0.56	4	4
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.087	-9999	-0.86	5	5
CASP3	0.043	0.025	-9999	-0.52	1	1
FN1	-0.05	0.23	-9999	-0.86	38	38
Syndecan-2/IL8	-0.036	0.14	-9999	-0.56	33	33
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.56	0.32	-9999	-0.75	379	379
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.019	0.15	-9999	-0.86	15	15
Syndecan-2/TGFB1	-0.006	0.057	-9999	-0.58	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-2/Ezrin	0	0	-9999	-10000	0	0
PRKACA	0.044	0	-9999	-10000	0	0
angiogenesis	-0.036	0.14	-9999	-0.56	33	33
MMP2	0.006	0.093	-9999	-0.84	6	6
IL8	-0.04	0.21	-9999	-0.84	33	33
calcineurin-NFAT signaling pathway	-0.056	0.17	-9999	-0.57	49	49

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.006	0.22	-10000	0	-0.88	3	3
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.086	0.12	-10000	0	-0.76	2	2
EDN1	-0.017	0.2	-10000	0	-0.76	18	18
EDN3	-0.02	0.16	-10000	0	-0.86	17	17
EDN2	-0.088	0.28	-10000	0	-0.82	63	63
HRAS/GDP	0.051	0.17	-10000	0	-0.7	9	9
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.021	0.15	-10000	0	-0.5	16	16
ADCY4	0.008	0.17	-10000	0	-0.74	3	3
ADCY5	-0.01	0.2	-10000	0	-0.69	14	14
ADCY6	0.007	0.17	-10000	0	-0.74	3	3
ADCY7	-0.007	0.19	-10000	0	-0.72	7	7
ADCY1	-0.002	0.18	-10000	0	-0.74	4	4
ADCY2	-0.12	0.27	-10000	0	-0.71	28	28
ADCY3	0.008	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.27	-10000	0	-0.74	33	33
ADCY9	0.008	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.077	0.15	-10000	0	-0.53	10	10
ETB receptor/Endothelin-1/Gq/GTP	0.035	0.11	-10000	0	-0.46	11	11
GNAO1	0.007	0.085	-10000	0	-0.84	5	5
HRAS	0.014	0.039	-10000	0	-0.86	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.016	0.22	0.38	69	-0.82	3	72
ETA receptor/Endothelin-1/Gs/GTP	-0.015	0.21	0.36	69	-0.79	3	72
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.046	0.34	-10000	0	-0.95	52	52
EDNRB	0.006	0.069	-10000	0	-0.78	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.045	0.3	-10000	0	-0.75	48	48
CYSLTR1	0.005	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.015	0.11	-10000	0	-0.39	2	2
mol:GDP	0.045	0.18	-10000	0	-0.7	11	11
SLC9A3	-0.35	0.3	-10000	0	-0.53	318	318
RAF1	0.047	0.17	-10000	0	-0.68	10	10
JUN	0.088	0.12	-10000	0	-0.57	1	1
JAK2	0.006	0.22	-10000	0	-0.88	3	3
mol:IP3	0.018	0.17	-10000	0	-0.58	16	16
ETA receptor/Endothelin-1	-0.029	0.28	0.45	69	-0.65	19	88
PLCB1	0.003	0.1	-10000	0	-0.75	9	9
PLCB2	-0.08	0.28	-10000	0	-0.86	56	56
ETA receptor/Endothelin-3	-0.024	0.15	-10000	0	-0.68	19	19
FOS	0.059	0.2	-10000	0	-0.86	15	15
Gai/GDP	0.038	0.07	-10000	0	-0.63	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.002	0.24	-10000	0	-0.77	16	16
BCAR1	0.014	0.034	-10000	0	-0.75	1	1
PRKCB1	0.019	0.16	-10000	0	-0.55	16	16
GNAQ	0.02	0.004	-10000	0	-10000	0	0
GNAZ	0.011	0.059	-10000	0	-0.75	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
Gs family/GDP	-0.044	0.11	-10000	0	-0.61	11	11
ETA receptor/Endothelin-1/Gq/GTP	0.044	0.14	-10000	0	-0.5	9	9
MAPK14	0.024	0.13	-10000	0	-0.56	10	10
TRPC6	0.086	0.13	-10000	0	-0.81	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.059	-10000	0	-0.75	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.015	0.14	-10000	0	-0.55	13	13
ETB receptor/Endothelin-2	-0.084	0.21	-10000	0	-0.62	66	66
ETB receptor/Endothelin-3	-0.03	0.13	-10000	0	-0.66	20	20
ETB receptor/Endothelin-1	-0.034	0.16	-10000	0	-0.62	19	19
MAPK3	0.06	0.19	-10000	0	-0.72	17	17
MAPK1	0.06	0.19	-10000	0	-0.72	17	17
Rac1/GDP	0.052	0.17	-10000	0	-0.71	8	8
cAMP biosynthetic process	-0.062	0.19	-10000	0	-0.65	10	10
MAPK8	0.08	0.13	-10000	0	-0.58	2	2
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.029	0.092	-10000	0	-0.57	3	3
p130Cas/CRK/Src/PYK2	0.073	0.17	-10000	0	-0.7	8	8
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.052	0.17	-10000	0	-0.68	9	9
COL1A2	-0.1	0.34	-10000	0	-0.88	67	67
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.079	0.22	-10000	0	-0.63	65	65
mol:DAG	0.018	0.17	-10000	0	-0.58	16	16
MAP2K2	0.057	0.18	-10000	0	-0.7	10	10
MAP2K1	0.057	0.17	-10000	0	-0.68	10	10
EDNRA	-0.009	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.017	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.033	0.14	-10000	0	-0.7	14	14
HRAS/GTP	0.036	0.17	-10000	0	-0.69	11	11
PRKCH	0.029	0.16	-10000	0	-0.6	12	12
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.029	0.16	-10000	0	-0.66	9	9
PRKCB	0.024	0.18	-10000	0	-0.71	13	13
PRKCE	0.028	0.16	-10000	0	-0.59	13	13
PRKCD	0.028	0.16	-10000	0	-0.64	10	10
PRKCG	0.003	0.2	-10000	0	-0.69	21	21
regulation of vascular smooth muscle contraction	0.058	0.23	-10000	0	-1	15	15
PRKCQ	0.016	0.18	-10000	0	-0.64	17	17
PLA2G4A	0.077	0.16	-10000	0	-0.57	10	10
GNA14	0.009	0.09	-10000	0	-0.75	7	7
GNA15	-0.006	0.14	-10000	0	-0.86	14	14
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.016	0.048	-10000	0	-0.75	2	2
Rac1/GTP	-0.015	0.22	0.38	69	-0.82	3	72
MMP1	-0.13	0.37	-10000	0	-0.85	99	99

×

Neurotrophic factor-mediated Trk receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.015	0.059	-10000	0	-0.62	1	1
NT3 (dimer)/TRKC	-0.041	0.16	-10000	0	-0.61	34	34
NT3 (dimer)/TRKB	-0.13	0.25	-10000	0	-0.54	125	125
SHC/Grb2/SOS1/GAB1/PI3K	-0.002	0.022	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.1	0.3	-10000	0	-0.86	68	68
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.045	0.21	-10000	0	-0.76	39	39
NTRK2	-0.13	0.3	-10000	0	-0.75	96	96
NTRK3	-0.03	0.18	-10000	0	-0.75	30	30
NT-4/5 (dimer)/TRKB	-0.13	0.25	-10000	0	-0.55	123	123
neuron apoptosis	0.14	0.18	0.57	48	-10000	0	48
SHC 2-3/Grb2	-0.16	0.2	-10000	0	-0.64	48	48
SHC1	0.014	0.039	-10000	0	-0.86	1	1
SHC2	-0.097	0.14	-10000	0	-0.52	33	33
SHC3	-0.16	0.24	-10000	0	-0.64	87	87
STAT3 (dimer)	0.013	0.067	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.081	0.2	-10000	0	-0.56	74	74
RIN/GDP	0.049	0.064	-10000	0	-0.32	1	1
GIPC1	0.014	0.034	-10000	0	-0.75	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.068	0.14	-10000	0	-0.63	13	13
RIN/GTP	-0.001	0.03	-10000	0	-0.68	1	1
CCND1	0.01	0.16	-10000	0	-0.78	19	19
MAGED1	0.014	0.039	-10000	0	-0.86	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.003	0.086	-10000	0	-0.86	5	5
SHC/GRB2/SOS1	-0.001	0.025	-10000	0	-0.57	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.14	0.27	-10000	0	-0.59	123	123
TRKA/NEDD4-2	-0.045	0.16	-10000	0	-0.58	39	39
ELMO1	0.012	0.055	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.003	0.043	-10000	0	-0.55	3	3
NGF	-0.066	0.25	-10000	0	-0.86	47	47
HRAS	0.014	0.039	-10000	0	-0.86	1	1
DOCK1	0.014	0.034	-10000	0	-0.75	1	1
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.002	0.039	-10000	0	-0.86	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	-0.002	0.12	-10000	0	-0.86	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.068	0.14	-10000	0	-0.59	15	15
mol:GDP	0.063	0.087	-10000	0	-0.48	2	2
NGF (dimer)	-0.065	0.25	-10000	0	-0.86	47	47
RhoG/GDP	-0.003	0.042	-10000	0	-0.68	2	2
RIT1/GDP	0.055	0.063	-10000	0	-0.31	1	1
TIAM1	0.014	0.034	-10000	0	-0.75	1	1
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
BDNF (dimer)/TRKB	-0.17	0.26	-10000	0	-0.55	152	152
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.002	0.039	-10000	0	-0.61	2	2
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.001	0.023	-10000	0	-0.52	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	0.005	0.093	-10000	0	-0.78	7	7
RAP1/GDP	-0.008	0.031	-10000	0	-10000	0	0
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.1	0.3	-10000	0	-0.86	68	68
ubiquitin-dependent protein catabolic process	-0.091	0.21	-10000	0	-0.55	84	84
Schwann cell development	-0.026	0.032	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.15	0.24	-10000	0	-0.82	30	30
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.05	0.078	-10000	0	-10000	0	0
STAT3	0.013	0.067	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.76	30	30
MAPK3	-0.096	0.26	-10000	0	-0.57	90	90
MAPK1	-0.096	0.26	-10000	0	-0.57	90	90
CDC42/GDP	0.055	0.063	-10000	0	-0.31	1	1
NTF3	0.005	0.093	-10000	0	-0.78	7	7
NTF4	-0.003	0.086	-10000	0	-0.86	5	5
NGF (dimer)/TRKA/FAIM	-0.09	0.2	-10000	0	-0.54	84	84
PI3K	-0.002	0.035	-10000	0	-0.56	2	2
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.078	0.16	-10000	0	-0.6	22	22
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0	0.14	-10000	0	-0.52	34	34
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.05	0.065	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.063	-10000	0	-0.31	1	1
NGF (dimer)/TRKA/GRIT	-0.092	0.21	-10000	0	-0.56	84	84
neuron projection morphogenesis	-0.02	0.14	-10000	0	-0.57	6	6
NGF (dimer)/TRKA/NEDD4-2	-0.091	0.21	-10000	0	-0.55	84	84
MAP2K1	0.053	0.024	-10000	0	-10000	0	0
NGFR	-0.042	0.22	-10000	0	-0.86	33	33
NGF (dimer)/TRKA/GIPC/GAIP	-0.054	0.12	-10000	0	-0.59	3	3
RAS family/GTP/PI3K	-0.002	0.03	-10000	0	-0.6	1	1
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.059	-10000	0	-0.75	3	3
MAPKKK cascade	-0.096	0.18	-10000	0	-0.61	44	44
RASA1	0.014	0.034	-10000	0	-0.75	1	1
TRKA/c-Abl	-0.044	0.15	-10000	0	-0.57	39	39
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.15	0.24	-10000	0	-0.6	67	67
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.078	0.18	-10000	0	-0.87	3	3
MATK	-0.068	0.26	-10000	0	-0.86	48	48
NEDD4L	0.014	0.034	-10000	0	-0.75	1	1
RAS family/GDP	-0.008	0.032	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.074	0.15	-10000	0	-0.48	35	35
Rac1/GTP	-0.044	0.084	-10000	0	-0.42	6	6
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.065	0.13	-9999	-0.6	8	8
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.014	0.16	-9999	-0.86	17	17
WNT4	-0.071	0.24	-9999	-0.75	57	57
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.059	-9999	-0.75	3	3
WNT11	-0.041	0.2	-9999	-0.76	37	37

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.014	0.035	-10000	0	-0.73	1	1
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.022	0.088	-10000	0	-0.52	4	4
AKT1	0.02	0.006	-10000	0	-10000	0	0
GSC	-0.028	0.23	-10000	0	-0.76	43	43
NKX2-5	-0.049	0.22	-10000	0	-0.86	34	34
muscle cell differentiation	0.034	0.11	0.57	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.037	0.079	-10000	0	-10000	0	0
SMAD4	0.032	0.03	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.003	0.047	-10000	0	-0.56	2	2
SMAD3/SMAD4/VDR	0.011	0.051	-10000	0	-10000	0	0
MYC	-0.03	0.16	-10000	0	-0.86	18	18
CDKN2B	0.055	0.091	-10000	0	-0.67	6	6
AP1	0.059	0.076	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.013	0.05	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.043	0.07	-10000	0	-0.53	1	1
SP3	0.02	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.06	0.25	-10000	0	-0.88	43	43
SMAD3/SMAD4/GR	0.009	0.045	-10000	0	-0.6	1	1
GATA3	-0.35	0.38	-10000	0	-0.74	244	244
SKI/SIN3/HDAC complex/NCoR1	0.054	0.044	-10000	0	-10000	0	0
MEF2C/TIF2	-0.076	0.2	-10000	0	-0.81	20	20
endothelial cell migration	0.095	0.26	0.73	72	-10000	0	72
MAX	0.018	0.017	-10000	0	-10000	0	0
RBBP7	0.015	0.005	-10000	0	-10000	0	0
RBBP4	0.013	0.034	-10000	0	-0.75	1	1
RUNX2	-0.009	0.14	-10000	0	-0.86	14	14
RUNX3	-0.35	0.43	-10000	0	-0.86	213	213
RUNX1	-0.048	0.23	-10000	0	-0.86	37	37
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.016	0.043	-10000	0	-0.87	1	1
VDR	0.011	0.059	-10000	0	-0.75	3	3
CDKN1A	0.083	0.075	-10000	0	-0.64	2	2
KAT2B	0.013	0.034	-10000	0	-0.74	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.054	0.18	-10000	0	-0.61	43	43
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.005	-10000	0	-10000	0	0
SERPINE1	-0.098	0.26	-10000	0	-0.74	72	72
SMAD3/SMAD4/ATF2	0.008	0.038	-10000	0	-0.48	1	1
SMAD3/SMAD4/ATF3	0.005	0.054	-10000	0	-0.49	4	4
SAP30	-0.016	0.16	-10000	0	-0.86	18	18
Cbp/p300/PIAS3	0.007	0.036	-10000	0	-0.45	1	1
JUN	0.074	0.073	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.01	0.11	-10000	0	-0.56	16	16
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	-0.095	0.25	-10000	0	-0.75	66	66
mesenchymal cell differentiation	0.007	0.1	0.59	14	-10000	0	14
DLX1	-0.45	0.44	-10000	0	-0.86	269	269
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.005	0.12	-10000	0	-0.74	13	13
SMAD3/SMAD4/Max	0.011	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	-0.001	0.02	-10000	0	-10000	0	0
ZBTB17	-0.002	0.046	-10000	0	-0.72	2	2
LAMC1	0.071	0.042	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.031	-10000	0	-10000	0	0
IRF7	-0.011	0.16	-10000	0	-0.85	17	17
ESR1	0.002	0.072	-10000	0	-0.76	4	4
HNF4A	-0.049	0.21	-10000	0	-0.75	43	43
MEF2C	-0.008	0.22	-10000	0	-0.8	20	20
SMAD2-3/SMAD4	0.005	0.032	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.005	0.029	-10000	0	-0.46	1	1
IGHV3OR16-13	-0.049	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.008	-10000	0	-10000	0	0
SKIL	0.016	0	-10000	0	-10000	0	0
HDAC1	0.015	0.005	-10000	0	-10000	0	0
HDAC2	0.015	0.005	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.01	0.036	-10000	0	-10000	0	0
MSG1/HSC70	0.002	0.044	-10000	0	-0.67	2	2
SMAD2	0.022	0.02	-10000	0	-10000	0	0
SMAD3	0.032	0.027	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.062	0.034	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.024	0.032	-10000	0	-0.53	1	1
NCOR1	0.015	0.005	-10000	0	-10000	0	0
NCOA2	0.004	0.095	-10000	0	-0.75	8	8
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.035	0.15	-10000	0	-0.66	27	27
SMAD2-3/SMAD4/SP1/MIZ-1	0.076	0.085	-10000	0	-10000	0	0
IFNB1	0.047	0.1	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.013	0.21	-10000	0	-0.78	18	18
CITED1	0.011	0.055	-10000	0	-0.86	2	2
SMAD2-3/SMAD4/ARC105	0.007	0.031	-10000	0	-10000	0	0
RBL1	0.016	0.001	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.076	0.065	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.28	0.32	-10000	0	-0.61	235	235
SMAD7	0.078	0.085	-10000	0	-10000	0	0
MYC/MIZ-1	-0.025	0.13	-10000	0	-0.65	20	20
SMAD3/SMAD4	-0.02	0.12	-10000	0	-10000	0	0
IL10	-0.19	0.31	-10000	0	-0.99	31	31
PIASy/HDAC complex	0.018	0.01	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.17	0.25	-10000	0	-0.75	15	15
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.018	0.01	-10000	0	-10000	0	0
ATF3	0.01	0.068	-10000	0	-0.75	4	4
SMAD3/SMAD4/SP1	-0.012	0.053	-10000	0	-10000	0	0
FOXG1	-0.026	0.17	-10000	0	-0.86	20	20
FOXO3	0.037	0.009	-10000	0	-10000	0	0
FOXO1	0.036	0.009	-10000	0	-10000	0	0
FOXO4	0.036	0.009	-10000	0	-10000	0	0
heart looping	-0.008	0.22	-10000	0	-0.79	20	20
CEBPB	-0.003	0.13	-10000	0	-0.86	12	12
SMAD3/SMAD4/DLX1	-0.31	0.29	-10000	0	-0.58	269	269
MYOD1	-0.04	0.2	-10000	0	-0.86	27	27
SMAD3/SMAD4/HNF4	-0.034	0.14	-10000	0	-0.51	29	29
SMAD3/SMAD4/GATA3	-0.23	0.25	-10000	0	-0.67	31	31
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.23	0.28	-10000	0	-0.72	39	39
SMAD3/SMAD4/SP1-3	-0.005	0.043	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.012	0.05	-10000	0	-10000	0	0
SIN3B	0.015	0.005	-10000	0	-10000	0	0
SIN3A	0.015	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.079	0.22	-10000	0	-0.79	28	28
ITGB5	0.084	0.065	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.014	0.11	-10000	0	-0.54	10	10
AR	-0.021	0.16	-10000	0	-0.75	24	24
negative regulation of cell growth	0.065	0.067	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.023	0.14	-10000	0	-0.6	27	27
E2F5	0.014	0.034	-10000	0	-0.75	1	1
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.042	0.15	-10000	0	-0.65	14	14
SMAD2-3/SMAD4/FOXO1-3a-4	0.077	0.044	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.007	0.069	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.007	0.1	-10000	0	-0.59	14	14
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.014	0.034	-10000	0	-0.75	1	1

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.004	0.12	-10000	0	-0.86	10	10
GNB1/GNG2	-0.034	0.063	-10000	0	-0.22	14	14
AKT1	0.054	0.1	-10000	0	-0.25	1	1
EGF	-0.67	0.23	-10000	0	-0.75	455	455
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.032	0.081	-10000	0	-0.61	2	2
mol:Ca2+	0.041	0.14	-10000	0	-0.33	26	26
LYN	-0.03	0.071	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.037	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.049	0.15	-10000	0	-0.37	24	24
GNG2	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.039	-10000	0	-0.86	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.076	-10000	0	-0.42	6	6
G beta5/gamma2	-0.045	0.083	-10000	0	-0.3	15	15
PRKCH	0.042	0.16	-10000	0	-0.39	21	21
DNM1	-0.002	0.12	-10000	0	-0.86	10	10
TXA2/TP beta/beta Arrestin3	-0.013	0.042	-10000	0	-0.27	10	10
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.11	0.31	-10000	0	-0.86	75	75
G12 family/GTP	-0.043	0.092	-10000	0	-0.32	26	26
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.016	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.03	0.11	0.31	12	-10000	0	12
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	-0.002	0.12	-10000	0	-0.75	12	12
mol:IP3	0.037	0.17	-10000	0	-0.42	26	26
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.027	0.22	-10000	0	-0.53	44	44
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.055	0.13	-10000	0	-0.6	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.052	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.013	0.052	-10000	0	-0.8	2	2
PRKCB1	0.037	0.16	-10000	0	-0.38	43	43
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.035	0.21	-10000	0	-0.53	43	43
LCK	-0.047	0.12	-10000	0	-0.6	12	12
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.041	0.096	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.028	0.036	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.041	0.096	-10000	0	-10000	0	0
MAPK14	0.054	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.036	0.19	-10000	0	-0.48	28	28
MAPK11	0.053	0.11	-10000	0	-0.38	2	2
ARHGEF1	0.041	0.088	-10000	0	-0.32	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.044	0.17	-10000	0	-0.39	43	43
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.044	0.13	-10000	0	-0.32	29	29
cAMP biosynthetic process	0.034	0.16	-10000	0	-0.39	30	30
Gq family/GTP/EBP50	0.026	0.058	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.03	0.071	-10000	0	-10000	0	0
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.087	0.1	-10000	0	-0.41	15	15
VCAM1	0.043	0.14	-10000	0	-0.33	33	33
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.076	-10000	0	-0.42	6	6
platelet activation	0.066	0.15	-10000	0	-0.34	15	15
PGI2/IP	-0.002	0.039	-10000	0	-0.62	2	2
PRKACA	-0.052	0.12	-10000	0	-0.34	77	77
Gq family/GDP/G beta5/gamma2	0.025	0.076	-10000	0	-0.42	6	6
TXA2/TP beta/beta Arrestin2	-0.013	0.059	-10000	0	-0.41	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.015	0.13	-10000	0	-10000	0	0
mol:DAG	0.036	0.18	-10000	0	-0.43	43	43
EGFR	0	0.11	-10000	0	-0.85	9	9
TXA2/TP alpha	0.033	0.21	-10000	0	-0.54	30	30
Gq family/GTP	-0.005	0.052	-10000	0	-0.27	6	6
YES1	-0.03	0.071	-10000	0	-10000	0	0
GNAI2/GTP	-0.035	0.083	-10000	0	-10000	0	0
PGD2/DP	-0.1	0.24	-10000	0	-0.68	75	75
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.03	0.071	-10000	0	-10000	0	0
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	-0.009	0.14	-10000	0	-0.86	14	14
PGK/cGMP	-0.012	0.075	-10000	0	-0.49	12	12
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.047	0.11	-10000	0	-0.71	1	1
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.042	0.16	-10000	0	-0.39	20	20
PRKCB	0.04	0.16	-10000	0	-0.43	22	22
PRKCE	0.043	0.16	-10000	0	-0.4	21	21
PRKCD	0.041	0.16	-10000	0	-0.38	40	40
PRKCG	0.029	0.19	-10000	0	-0.44	48	48
muscle contraction	0.042	0.2	-10000	0	-0.49	43	43
PRKCZ	0.049	0.16	-10000	0	-0.37	26	26
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.04	0.094	-10000	0	-10000	0	0
PRKCQ	0.034	0.17	-10000	0	-0.41	27	27
MAPKKK cascade	0.035	0.19	-10000	0	-0.46	42	42
SELE	0.037	0.16	-10000	0	-0.41	40	40
TP beta/GNAI2/GDP/G beta/gamma	-0.038	0.09	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.005	0.089	-10000	0	-0.75	7	7
chemotaxis	0.035	0.23	-10000	0	-0.61	42	42
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.013	0.048	-10000	0	-0.75	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.015	0.088	-9999	-0.52	15	15
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.014	0.034	-9999	-0.75	1	1
ITGA4	-0.01	0.15	-9999	-0.86	15	15
alpha4/beta7 Integrin/MAdCAM1	-0.028	0.12	-9999	-0.52	27	27
EPO	-0.29	0.42	-9999	-0.86	178	178
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	15	15
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.66	178	178
lamellipodium assembly	0	0.036	-9999	-0.53	2	2
PIK3CA	0.014	0.034	-9999	-0.75	1	1
PI3K	-0.002	0.035	-9999	-0.56	2	2
ARF6	0.016	0	-9999	-10000	0	0
JAK2	-0.12	0.16	-9999	-0.66	5	5
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
MADCAM1	-0.008	0.13	-9999	-0.86	12	12
cell adhesion	-0.028	0.12	-9999	-0.52	27	27
CRKL/CBL	-0.001	0.025	-9999	-0.56	1	1
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.014	0.13	-9999	-0.52	24	24
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.032	0.13	-9999	-0.56	29	29
p130Cas/Crk/Dock1	-0.025	0.1	-9999	-0.8	1	1
VCAM1	-0.007	0.14	-9999	-0.82	14	14
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.015	0.088	-9999	-0.52	15	15
BCAR1	0.025	0.13	-9999	-0.5	24	24
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0.034	-9999	-0.75	1	1
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0	0.038	-9999	-0.55	2	2

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.04	0.045	-9999	-10000	0	0
GNAO1	0.01	0.085	-9999	-0.84	5	5
S1P/S1P3/G12/G13	-0.001	0.019	-9999	-0.44	1	1
AKT1	-0.002	0.013	-9999	-10000	0	0
AKT3	-0.024	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	0.013	0.059	-9999	-0.75	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.034	-9999	-0.75	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.053	0.05	-9999	-0.54	1	1
MAPK3	0.062	0.047	-9999	-0.5	1	1
MAPK1	0.062	0.047	-9999	-0.5	1	1
JAK2	-0.021	0.13	-9999	-0.48	2	2
CXCR4	-0.12	0.25	-9999	-0.47	171	171
FLT1	0.01	0.087	-9999	-0.86	5	5
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.062	0.047	-9999	-0.5	1	1
S1P/S1P3/Gi	0.053	0.05	-9999	-0.54	1	1
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.036	-9999	-0.49	1	1
VEGFA	-0.37	0.44	-9999	-0.86	225	225
S1P/S1P2/Gi	0.049	0.044	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	226	226
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.028	0.07	-9999	-10000	0	0
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.059	-9999	-0.75	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.005	0.089	-9999	-0.75	7	7
GNA15	-0.009	0.14	-9999	-0.86	14	14
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.013	0.048	-9999	-0.75	2	2
Rac1/GTP	-0.005	0.036	-9999	-0.49	1	1

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.001	0.029	-10000	0	-0.66	1	1
HDAC1	0.003	0.011	-10000	0	-10000	0	0
AES	0.005	0.008	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.057	0.22	-10000	0	-0.75	48	48
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.015	0.002	-10000	0	-10000	0	0
AP1	-0.096	0.16	-10000	0	-0.34	141	141
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.014	0.034	-10000	0	-0.75	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.012	0.067	-10000	0	-0.45	1	1
NICD/RBPSUH	-0.001	0.028	-10000	0	-0.64	1	1
WIF1	0.001	0.078	-10000	0	-0.77	5	5
NOTCH1	-0.001	0.03	-10000	0	-0.68	1	1
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.089	0.28	-10000	0	-0.86	60	60
DKK1	-0.018	0.16	-10000	0	-0.83	20	20
beta catenin/beta TrCP1	0.083	0.084	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	-0.011	0.035	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.007	0.048	-10000	0	-10000	0	0
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.004	0.12	-10000	0	-0.76	13	13
JUN	0.016	0	-10000	0	-10000	0	0
MAP3K7	0.002	0.007	-10000	0	-10000	0	0
CTNNB1	0.079	0.091	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.094	0.21	-10000	0	-0.57	83	83
HNF1A	-0.003	0.075	-10000	0	-0.75	5	5
CTBP1	0.005	0.008	-10000	0	-10000	0	0
MYC	0.005	0.14	-10000	0	-0.73	18	18
NKD1	-0.18	0.34	-10000	0	-0.75	132	132
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.038	0.12	-10000	0	-0.64	1	1
apoptosis	-0.095	0.16	-10000	0	-0.34	141	141
Delta 1/NOTCHprecursor	-0.001	0.028	-10000	0	-0.64	1	1
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.029	0.022	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.011	0.035	-10000	0	-10000	0	0
DVL1	-0.005	0.033	-10000	0	-0.47	2	2
CSNK2A1	0.015	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.089	0.22	-10000	0	-0.62	73	73
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
NLK	0.015	0.013	-10000	0	-10000	0	0
CCND1	0.004	0.15	-10000	0	-0.73	19	19
WNT1	-0.027	0.19	-10000	0	-0.86	24	24
Axin1/APC/beta catenin	0.081	0.052	-10000	0	-10000	0	0
DKK2	-0.025	0.18	-10000	0	-0.83	24	24
NOTCH1 precursor/DVL1	-0.003	0.034	-10000	0	-0.58	1	1
GSK3B	0.012	0.007	-10000	0	-10000	0	0
FRAT1	0.012	0.007	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.038	0.12	-10000	0	-0.66	1	1
PPP2R5D	0.091	0.16	0.36	131	-10000	0	131
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.029	0.12	-10000	0	-0.52	25	25
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	-0.021	0.089	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
AP1	-0.031	0.1	-9999	-0.6	1	1
mol:PIP3	-0.027	0.092	-9999	-0.55	1	1
AKT1	-0.014	0.058	-9999	-10000	0	0
PTK2B	0.033	0.06	-9999	-10000	0	0
RHOA	0.036	0.035	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.051	0.052	-9999	-0.48	1	1
MAGI3	0.013	0.048	-9999	-0.75	2	2
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.022	0.086	-9999	-0.38	26	26
HRAS/GDP	-0.001	0.03	-9999	-0.68	1	1
positive regulation of microtubule depolymerization	0.046	0.07	-9999	-0.38	3	3
NF kappa B1 p50/RelA	-0.019	0.074	-9999	-10000	0	0
endothelial cell migration	0.006	0.14	-9999	-0.54	28	28
ADCY4	0.031	0.12	-9999	-0.47	24	24
ADCY5	0.022	0.13	-9999	-0.49	27	27
ADCY6	0.031	0.12	-9999	-0.47	24	24
ADCY7	0.026	0.13	-9999	-0.48	24	24
ADCY1	0.026	0.13	-9999	-0.48	25	25
ADCY2	-0.018	0.14	-9999	-0.52	24	24
ADCY3	0.031	0.12	-9999	-0.47	24	24
ADCY8	-0.028	0.14	-9999	-0.49	24	24
ADCY9	0.031	0.12	-9999	-0.47	24	24
GSK3B	0.042	0.057	-9999	-10000	0	0
arachidonic acid secretion	0.038	0.11	-9999	-0.44	22	22
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0.001	0.008	-9999	-10000	0	0
GNAO1	0.006	0.12	-9999	-0.48	27	27
HRAS	0.014	0.039	-9999	-0.86	1	1
NFKBIA	0.061	0.062	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.054	-9999	-0.86	2	2
JUN	0.016	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.002	0.023	-9999	-0.48	1	1
TIAM1	-0.003	0.064	-9999	-1	2	2
PIK3R1	0.014	0.034	-9999	-0.75	1	1
mol:IP3	0.051	0.053	-9999	-0.49	1	1
PLCB3	0.037	0.024	-9999	-0.43	1	1
FOS	-0.004	0.12	-9999	-0.76	13	13
positive regulation of mitosis	0.038	0.11	-9999	-0.44	22	22
LPA/LPA1-2-3	-0.026	0.1	-9999	-0.44	26	26
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0.034	-9999	-0.75	1	1
stress fiber formation	0.039	0.077	-9999	-10000	0	0
GNAZ	0.009	0.12	-9999	-0.48	25	25
EGFR/PI3K-beta/Gab1	-0.028	0.096	-9999	-0.57	1	1
positive regulation of dendritic cell cytokine production	-0.026	0.1	-9999	-0.44	26	26
LPA/LPA2/MAGI-3	-0.003	0.032	-9999	-0.48	2	2
ARHGEF1	0.03	0.096	-9999	-0.49	1	1
GNAI2	0.012	0.11	-9999	-0.47	22	22
GNAI3	0.012	0.11	-9999	-0.47	22	22
GNAI1	0.009	0.12	-9999	-0.48	25	25
LPA/LPA3	-0.007	0.061	-9999	-0.67	4	4
LPA/LPA2	-0.001	0.013	-9999	-10000	0	0
LPA/LPA1	-0.028	0.12	-9999	-0.51	28	28
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	249	249
HBEGF	-0.3	0.35	-9999	-0.66	243	243
mol:DAG	0.051	0.053	-9999	-0.49	1	1
cAMP biosynthetic process	0.019	0.12	-9999	-0.46	23	23
NFKB1	0.014	0.034	-9999	-0.75	1	1
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.061	0.062	-9999	-10000	0	0
GNAQ	-0.004	0.036	-9999	-0.4	4	4
LPAR2	0.016	0	-9999	-10000	0	0
LPAR3	0.003	0.078	-9999	-0.86	4	4
LPAR1	-0.013	0.16	-9999	-0.73	22	22
IL8	-0.081	0.2	-9999	-0.48	43	43
PTK2	0.024	0.1	-9999	-0.48	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.022	0.086	-9999	-0.38	26	26
EGFR	0	0.11	-9999	-0.85	9	9
PLCG1	0.019	0.054	-9999	-0.41	4	4
PLD2	0.024	0.1	-9999	-0.48	4	4
G12/G13	-0.021	0.089	-9999	-0.42	22	22
PI3K-beta	-0.016	0.068	-9999	-0.52	1	1
cell migration	-0.009	0.035	-9999	-10000	0	0
SLC9A3R2	0.014	0.034	-9999	-0.75	1	1
PXN	0.039	0.078	-9999	-10000	0	0
HRAS/GTP	-0.026	0.099	-9999	-0.45	22	22
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.41	0.44	-9999	-0.86	243	243
PRKCE	0.013	0.034	-9999	-0.75	1	1
PRKCD	0.059	0.055	-9999	-10000	0	0
Gi(beta/gamma)	-0.026	0.098	-9999	-0.44	24	24
mol:LPA	0.003	0.024	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.018	0.081	-9999	-10000	0	0
MAPKKK cascade	0.038	0.11	-9999	-0.44	22	22
contractile ring contraction involved in cytokinesis	0.036	0.035	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.009	0.06	-9999	-0.4	11	11
GNA15	-0.015	0.078	-9999	-0.42	17	17
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.046	0.071	-9999	-0.39	3	3
GNA11	-0.006	0.043	-9999	-0.39	6	6
Rac1/GTP	-0.002	0.058	-9999	-0.91	2	2
MMP2	0.006	0.14	-9999	-0.54	28	28

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.016	0.16	-9999	-0.86	18	18
PLK4	0.01	0.067	-9999	-0.86	3	3
regulation of centriole replication	0.002	0.14	-9999	-0.66	21	21

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.045	-10000	0	-0.56	3	3
MAP4K4	0.025	0.094	-10000	0	-0.48	1	1
BAG4	0.014	0.034	-10000	0	-0.75	1	1
PKC zeta/ceramide	-0.099	0.047	-10000	0	-0.48	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.12	0.32	-10000	0	-0.86	78	78
BAX	-0.042	0.019	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.046	0.008	-10000	0	-10000	0	0
BAD	-0.098	0.043	-10000	0	-0.45	2	2
SMPD1	0.026	0.042	-10000	0	-0.28	1	1
RB1	-0.096	0.038	-10000	0	-10000	0	0
FADD/Caspase 8	0.04	0.088	-10000	0	-10000	0	0
MAP2K4	-0.081	0.036	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.085	0.058	-10000	0	-0.59	4	4
EGF	-0.67	0.23	-10000	0	-0.75	455	455
mol:ceramide	-0.12	0.04	0.2	2	-10000	0	2
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.03	0.026	-10000	0	-0.56	1	1
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.095	0.038	-10000	0	-10000	0	0
cell proliferation	-0.053	0.061	-10000	0	-0.46	10	10
BID	-0.012	0.066	-10000	0	-10000	0	0
MAP3K1	-0.096	0.038	-10000	0	-10000	0	0
EIF2A	-0.067	0.034	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.065	0.053	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.065	0.053	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.097	0.036	-10000	0	-0.27	1	1
FADD	0.025	0.094	-10000	0	-0.48	1	1
KSR1	-0.1	0.061	-10000	0	-0.63	4	4
MAPK8	-0.075	0.038	-10000	0	-0.34	2	2
PRKRA	-0.096	0.038	-10000	0	-10000	0	0
PDGFA	0.014	0.034	-10000	0	-0.75	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.005	0.095	-10000	0	-0.86	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.04	0.2	2	-10000	0	2
CTSD	0.014	0.034	-10000	0	-0.75	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.025	-10000	0	-0.56	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.055	0.067	-10000	0	-0.5	10	10
PRKCD	0.014	0.039	-10000	0	-0.86	1	1
PRKCZ	0.011	0.059	-10000	0	-0.75	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.03	0.026	-10000	0	-0.56	1	1
RelA/NF kappa B1	-0.001	0.025	-10000	0	-0.56	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.034	-10000	0	-0.75	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.034	0.078	-10000	0	-0.51	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.069	-10000	0	-0.52	9	9
mol:Sphingosine-1-phosphate	0.027	0.045	-10000	0	-0.56	3	3
MAP2K1	-0.071	0.055	-10000	0	-0.55	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	-0.063	0.024	-10000	0	-0.23	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.014	0.034	-10000	0	-0.75	1	1
TNFR1A/BAG4	-0.001	0.025	-10000	0	-0.56	1	1
EIF2AK2	-0.081	0.036	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.008	0.066	-10000	0	-0.52	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.037	-10000	0	-10000	0	0
MAP2K2	-0.072	0.054	-10000	0	-0.55	4	4
SMPD3	0.026	0.052	-10000	0	-0.33	2	2
TNF	0.003	0.1	-10000	0	-0.8	8	8
PKC zeta/PAR4	-0.004	0.05	-10000	0	-0.56	4	4
mol:PHOSPHOCHOLINE	0.23	0.083	0.26	455	-10000	0	455
NF kappa B1/RelA/I kappa B alpha	-0.004	0.039	-10000	0	-10000	0	0
AIFM1	-0.063	0.025	-10000	0	-0.23	1	1
BCL2	0.016	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0.048	-9999	-0.75	2	2
SPHK1	-0.055	0.24	-9999	-0.86	41	41
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0.094	-9999	-0.3	43	43
GNAO1	0.007	0.085	-9999	-0.84	5	5
mol:Sphinganine-1-P	-0.028	0.19	-9999	-0.66	43	43
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.017	0.055	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.014	0.034	-9999	-0.75	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.022	0.073	-9999	-0.29	2	2
S1PR5	-0.13	0.32	-9999	-0.86	83	83
S1PR4	-0.026	0.19	-9999	-0.86	24	24
GNAI1	0.011	0.059	-9999	-0.75	3	3
S1P/S1P5/G12	-0.1	0.2	-9999	-0.54	83	83
S1P/S1P3/Gq	0.025	0.096	-9999	-0.42	16	16
S1P/S1P4/Gi	0.025	0.095	-9999	-0.38	12	12
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.059	-9999	-0.75	3	3
GNA14	0.005	0.089	-9999	-0.75	7	7
GNA15	-0.009	0.14	-9999	-0.86	14	14
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.013	0.048	-9999	-0.75	2	2
ABCC1	0.016	0	-9999	-10000	0	0

×

FoxO family signaling

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
G6PC	-0.57	0.68	-9999	-1.3	236	236
PLK1	-0.13	0.37	-9999	-0.79	93	93
CDKN1B	0.061	0.16	-9999	-10000	0	0
FOXO3	-0.039	0.23	-9999	-0.66	14	14
KAT2B	0.012	0.041	-9999	-0.79	1	1
FOXO1/SIRT1	-0.14	0.21	-9999	-10000	0	0
CAT	-0.028	0.23	-9999	-0.89	7	7
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	-0.007	0.038	-9999	-10000	0	0
FOXO1	-0.16	0.23	-9999	-0.41	153	153
MAPK10	0.032	0.05	-9999	-0.43	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.045	-9999	-10000	0	0
response to oxidative stress	-0.029	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.025	0.2	-9999	-0.62	7	7
XPO1	0.017	0.001	-9999	-10000	0	0
EP300	-0.006	0.042	-9999	-0.75	1	1
BCL2L11	0.012	0.044	-9999	-10000	0	0
FOXO1/SKP2	-0.14	0.21	-9999	-10000	0	0
mol:GDP	-0.029	0.045	-9999	-10000	0	0
RAN	0.018	0.001	-9999	-10000	0	0
GADD45A	0.12	0.099	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.031	0.086	-9999	-10000	0	0
MST1	0	0.11	-9999	-0.86	8	8
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.097	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.038	0.019	-9999	-10000	0	0
MAPK9	0.037	0.019	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.035	0.028	-9999	-10000	0	0
SOD2	0.013	0.21	-9999	-0.7	6	6
RBL2	0.022	0.17	-9999	-1.3	1	1
RAL/GDP	0.009	0.024	-9999	-10000	0	0
CHUK	0.013	0.02	-9999	-10000	0	0
Ran/GTP	0.017	0.004	-9999	-10000	0	0
CSNK1G2	0.014	0.034	-9999	-0.75	1	1
RAL/GTP	0.024	0.026	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.34	0.39	-9999	-0.72	254	254
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.018	0.002	-9999	-10000	0	0
IKBKB	0.013	0.02	-9999	-10000	0	0
CCNB1	-0.031	0.24	-9999	-0.92	10	10
FOXO1-3a-4/beta catenin	-0.07	0.1	-9999	-0.43	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.013	0.02	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.014	-9999	-10000	0	0
ZFAND5	0.11	0.042	-9999	-10000	0	0
SFN	-0.086	0.28	-9999	-0.83	61	61
CDK2	-0.018	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.012	0.1	-9999	-10000	0	0
CREBBP	-0.018	0.041	-9999	-10000	0	0
FBXO32	-0.027	0.22	-9999	-0.79	8	8
BCL6	0.024	0.16	-9999	-10000	0	0
RALB	0.018	0	-9999	-10000	0	0
RALA	0.018	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.012	0.043	-10000	0	-10000	0	0
RFC1	0.012	0.043	-10000	0	-10000	0	0
PRKDC	0.012	0.043	-10000	0	-10000	0	0
RIPK1	0.014	0.005	-10000	0	-10000	0	0
CASP7	-0.023	0.066	0.25	6	-10000	0	6
FASLG/FAS/FADD/FAF1	-0.13	0.16	-10000	0	-0.35	22	22
MAP2K4	-0.084	0.16	-10000	0	-0.43	23	23
mol:ceramide	-0.15	0.2	-10000	0	-0.48	31	31
GSN	0.012	0.043	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.17	0.18	-10000	0	-0.44	22	22
FAS	0.015	0.006	-10000	0	-10000	0	0
BID	0.019	0.067	-10000	0	-10000	0	0
MAP3K1	-0.035	0.1	-10000	0	-10000	0	0
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
RB1	0.012	0.043	-10000	0	-10000	0	0
CFLAR	0.014	0.005	-10000	0	-10000	0	0
HGF/MET	-0.038	0.15	-10000	0	-0.58	33	33
ARHGDIB	0.012	0.043	-10000	0	-10000	0	0
FADD	0.015	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.043	-10000	0	-10000	0	0
NFKB1	-0.065	0.077	-10000	0	-0.71	1	1
MAPK8	-0.082	0.18	-10000	0	-0.52	23	23
DFFA	0.012	0.043	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.012	0.043	-10000	0	-10000	0	0
FAS/FADD/MET	-0.006	0.057	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.046	0.22	-10000	0	-0.86	36	36
FAF1	0.015	0.006	-10000	0	-10000	0	0
PARP1	0.012	0.043	-10000	0	-10000	0	0
DFFB	0.012	0.043	-10000	0	-10000	0	0
CHUK	-0.053	0.067	-10000	0	-0.66	1	1
FASLG	-0.43	0.44	-10000	0	-0.86	254	254
FAS/FADD	0	0	-10000	0	-10000	0	0
HGF	-0.021	0.17	-10000	0	-0.8	23	23
LMNA	0.01	0.047	-10000	0	-0.52	1	1
CASP6	0.012	0.043	-10000	0	-10000	0	0
CASP10	0.015	0.006	-10000	0	-10000	0	0
CASP3	0.014	0.05	-10000	0	-10000	0	0
PTPN13	0.002	0.1	-10000	0	-0.75	9	9
CASP8	0.029	0.1	0.4	36	-10000	0	36
IL6	-0.13	0.33	-10000	0	-0.96	63	63
MET	0.007	0.087	-10000	0	-0.86	5	5
ICAD/CAD	0.012	0.043	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.15	0.2	-10000	0	-0.49	31	31
activation of caspase activity by cytochrome c	0.019	0.067	-10000	0	-10000	0	0
PAK2	0.012	0.043	-10000	0	-10000	0	0
BCL2	0.016	0.001	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.001	0.017	-9999	-10000	0	0
DAPP1	0.029	0.11	-9999	-0.54	9	9
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.14	0.26	-9999	-0.74	53	53
mol:DAG	-0.069	0.15	-9999	-0.31	60	60
HRAS	0.015	0.039	-9999	-0.86	1	1
RAP1A	0.017	0.001	-9999	-10000	0	0
ARF5/GDP	0.019	0.073	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	-0.001	0.019	-9999	-10000	0	0
ARF1/GTP	-0.001	0.017	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.019	-9999	-10000	0	0
ADAP1	-0.004	0.037	-9999	-10000	0	0
ARAP3	-0.001	0.019	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0.001	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.011	0.067	-9999	-0.86	3	3
mol:Ca2+	-0.022	0.078	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.014	0.034	-9999	-0.75	1	1
ZAP70	-0.45	0.44	-9999	-0.86	270	270
mol:IP3	-0.035	0.11	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.019	0.073	-9999	-10000	0	0
RhoA/GDP	-0.004	0.017	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.021	-9999	-10000	0	0
BLNK	0.014	0.034	-9999	-0.75	1	1
actin cytoskeleton reorganization	0.045	0.081	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.036	0.054	-9999	-0.57	4	4
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.017	-9999	-10000	0	0
RhoA/GTP	-0.001	0.018	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.2	0.24	-9999	-0.56	128	128
BLK	-0.04	0.21	-9999	-0.86	32	32
PDPK1	0.014	0.034	-9999	-0.75	1	1
CYTH1	-0.001	0.018	-9999	-10000	0	0
HCK	-0.033	0.2	-9999	-0.86	28	28
CYTH3	-0.001	0.018	-9999	-10000	0	0
CYTH2	-0.001	0.018	-9999	-10000	0	0
KRAS	0.017	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.001	0.024	-9999	-0.54	1	1
SGK1	-0.001	0.027	-9999	-0.6	1	1
INPP5D	0.009	0.078	-9999	-0.86	4	4
mol:GDP	0.01	0.077	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.013	0.048	-9999	-0.75	2	2
ARF6/GDP	-0.004	0.017	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.019	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.001	0.019	-9999	-10000	0	0
VAV1	-0.19	0.37	-9999	-0.86	119	119
mol:PI-3-4-P2	0.025	0.062	-9999	-0.66	4	4
RAS family/GTP/PI3K Class I	-0.001	0.02	-9999	-10000	0	0
PLEKHA1	0.036	0.054	-9999	-0.57	4	4
Rac1/GDP	0.019	0.073	-9999	-10000	0	0
LAT	-0.23	0.4	-9999	-0.86	144	144
Rac1/GTP	0	0.1	-9999	-10000	0	0
ITK	-0.14	0.21	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.11	0.21	-9999	-0.46	77	77
LCK	-0.022	0.18	-9999	-0.85	22	22
BTK	-0.096	0.18	-9999	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.023	0.1	-9999	-0.5	23	23
E-cadherin/beta catenin	-0.023	0.11	-9999	-0.56	21	21
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.011	0.059	-9999	-0.75	3	3
CDH1	-0.016	0.15	-9999	-0.75	21	21

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.071	-10000	0	-0.4	1	1
epithelial cell differentiation	-0.05	0.11	-10000	0	-0.57	1	1
ITCH	0.055	0.018	-10000	0	-10000	0	0
WWP1	-0.097	0.067	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	0	0.11	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.019	0.081	-10000	0	-0.57	1	1
PTPRZ1	-0.079	0.25	-10000	0	-0.76	59	59
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.054	0.074	-10000	0	-0.6	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.084	0.094	-10000	0	-0.58	9	9
ADAM17	0.055	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.086	-10000	0	-0.47	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.61	11	11
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.076	0.078	-10000	0	-0.54	9	9
GRIN2B	-0.057	0.092	-10000	0	-0.61	3	3
ErbB4/ErbB2/betacellulin	-0.13	0.16	-10000	0	-0.52	68	68
STAT1	0.014	0.039	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.081	0.25	-10000	0	-0.75	64	64
E4ICDs/ETO2	-0.11	0.08	-10000	0	-0.7	2	2
axon guidance	-0.018	0.071	-10000	0	-10000	0	0
NEDD4	0.052	0.052	-10000	0	-0.73	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.072	0.19	-10000	0	-0.57	64	64
CBFA2T3	0.012	0.055	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.065	0.039	-10000	0	-0.52	1	1
MAPK3	-0.03	0.083	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.11	0.073	-10000	0	-0.54	1	1
MAPK1	-0.03	0.083	-10000	0	-0.6	1	1
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.078	0.082	-10000	0	-0.54	10	10
NRG1	0.035	0.11	-10000	0	-0.56	16	16
NRG3	-0.002	0.12	-10000	0	-0.86	10	10
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
NRG4	-0.056	0.22	-10000	0	-0.77	45	45
heart development	-0.018	0.071	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.081	-10000	0	-0.53	10	10
ERBB2	0.052	0.04	-10000	0	-0.56	2	2
WWOX/E4ICDs	-0.11	0.076	-10000	0	-0.55	2	2
SHC1	0.014	0.039	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.15	0.15	-10000	0	-0.57	49	49
apoptosis	0.1	0.062	0.38	6	-10000	0	6
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.089	-10000	0	-0.52	11	11
ErbB4/ErbB2/epiregulin	-0.099	0.13	-10000	0	-0.57	34	34
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.18	-10000	0	-0.59	75	75
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.13	0.14	-10000	0	-0.51	49	49
MDM2	-0.1	0.074	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.054	0.078	-10000	0	-0.52	9	9
STAT5A	-0.006	0.066	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.085	0.1	-10000	0	-0.56	17	17
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.029	-10000	0	-0.66	1	1
E4ICDs/TAB2/NCoR1	-0.1	0.048	-10000	0	-10000	0	0
STAT5A (dimer)	-0.053	0.12	-10000	0	-0.62	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.008	0.063	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.042	0.22	-10000	0	-0.86	33	33
BTC	-0.098	0.27	-10000	0	-0.75	75	75
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.018	0.071	-10000	0	-10000	0	0
ERBB4	-0.14	0.086	-10000	0	-0.47	1	1
STAT5B	0.016	0	-10000	0	-10000	0	0
YAP1	-0.034	0.016	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.1	0.13	-10000	0	-0.51	42	42
glial cell differentiation	0.1	0.048	-10000	0	-10000	0	0
WWOX	0.014	0.039	-10000	0	-0.86	1	1
cell proliferation	-0.075	0.16	-10000	0	-0.63	10	10

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.2	0.22	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.15	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.028	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.1	0.09	-9999	-0.37	1	1
CaM/Ca2+	-0.18	0.2	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.18	0.2	-9999	-1	1	1
AKT1	-0.16	0.17	-9999	-10000	0	0
MAP2K1	-0.13	0.22	-9999	-10000	0	0
MAP3K11	-0.15	0.23	-9999	-0.8	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.27	0.29	-9999	-0.74	107	107
Rap1/GTP	-0.13	0.14	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.21	0.23	-9999	-10000	0	0
CEBPB	-0.069	0.2	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.2	0.21	-9999	-1	2	2
STAT1	-0.15	0.23	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.38	0.43	-9999	-0.85	230	230
PIK3CA	0.014	0.034	-9999	-0.75	1	1
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.075	0.084	-9999	-0.47	1	1
mol:Ca2+	-0.19	0.21	-9999	-10000	0	0
MAPK3	-0.089	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.089	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
JAK1	0.001	0.019	-9999	-10000	0	0
CAMK2D	0.016	0	-9999	-10000	0	0
DAPK1	-0.026	0.15	-9999	-0.63	3	3
SMAD7	-0.021	0.081	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.17	0.19	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.85	230	230
apoptosis	-0.037	0.12	-9999	-0.44	3	3
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.24	0.36	-9999	-0.75	166	166
CAMK2B	-0.1	0.28	-9999	-0.76	76	76
FRAP1	-0.11	0.2	-9999	-10000	0	0
PRKCD	-0.12	0.21	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.1	0.09	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.015	0.034	-9999	-0.74	1	1
IRF1	-0.059	0.19	-9999	-0.93	1	1
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.01	0.084	-9999	-0.73	6	6
mol:GDP	-0.16	0.17	-9999	-10000	0	0
CASP1	-0.021	0.081	-9999	-10000	0	0
PTGES2	0.013	0.048	-9999	-0.75	2	2
IRF9	0.017	0.076	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.18	-9999	-10000	0	0
RAP1/GDP	-0.13	0.14	-9999	-10000	0	0
CBL	-0.15	0.23	-9999	-10000	0	0
MAP3K1	-0.15	0.23	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.1	0.09	-9999	-0.37	1	1
PTPN11	-0.16	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.018	-10000	0	-10000	0	0
AES	0.004	0.016	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.025	0.18	-10000	0	-0.83	24	24
TLE1	0.004	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.001	-10000	0	-10000	0	0
CTNNB1	0.049	0.099	-10000	0	-0.44	1	1
WIF1	-0.001	0.077	-10000	0	-0.77	5	5
beta catenin/RanBP3	0.003	0.1	0.36	18	-10000	0	18
KREMEN2	-0.089	0.28	-10000	0	-0.86	60	60
DKK1	-0.018	0.16	-10000	0	-0.83	20	20
beta catenin/beta TrCP1	0.056	0.093	-10000	0	-10000	0	0
FZD1	0.016	0.004	-10000	0	-10000	0	0
AXIN2	0.01	0.1	-10000	0	-1.4	2	2
AXIN1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.017	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.072	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.039	0.082	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.003	0.076	-10000	0	-0.74	5	5
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.007	0.15	-10000	0	-0.75	18	18
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.094	0.21	-10000	0	-0.57	83	83
NKD1	-0.18	0.34	-10000	0	-0.75	132	132
TCF4	0.005	0.017	-10000	0	-10000	0	0
TCF3	0.005	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.025	0.11	-10000	0	-0.52	24	24
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.1	0.52	3	-10000	0	3
LEF1	-0.021	0.15	-10000	0	-0.87	15	15
DVL1	0.003	0.034	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.082	0.07	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.089	0.22	-10000	0	-0.62	73	73
LRP6	0.016	0.002	-10000	0	-10000	0	0
CSNK1A1	0.005	0.018	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.008	0.15	-10000	0	-0.75	19	19
WNT1	-0.027	0.19	-10000	0	-0.86	24	24
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.016	0.002	-10000	0	-10000	0	0
FRAT1	0.014	0.005	-10000	0	-10000	0	0
PPP2R5D	0.094	0.15	0.35	131	-10000	0	131
APC	-0.017	0.1	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.012	0.063	0.27	5	-10000	0	5
CREBBP	0.005	0.017	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.021	0.093	-10000	0	-0.44	24	24
regulation of S phase of mitotic cell cycle	-0.015	0.069	-10000	0	-0.62	1	1
GNAO1	0.007	0.085	-10000	0	-0.84	5	5
HRAS	0.014	0.039	-10000	0	-0.86	1	1
SHBG/T-DHT	-0.051	0.15	-10000	0	-0.5	52	52
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.047	0.092	-10000	0	-10000	0	0
T-DHT/AR	-0.027	0.12	-10000	0	-0.57	24	24
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	13	13
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.059	-10000	0	-0.75	3	3
mol:GDP	-0.027	0.12	-10000	0	-0.56	24	24
cell proliferation	0.071	0.11	-10000	0	-0.64	4	4
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
FOS	0.056	0.15	-10000	0	-0.81	13	13
mol:Ca2+	-0.003	0.015	-10000	0	-0.11	4	4
MAPK3	0.063	0.1	-10000	0	-0.57	4	4
MAPK1	0.044	0.055	-10000	0	-0.29	4	4
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
mol:IP3	0	0.001	-10000	0	-0.004	13	13
cAMP biosynthetic process	-0.046	0.15	-10000	0	-0.48	52	52
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	13	13
HRAS/GTP	-0.02	0.086	-10000	0	-0.45	5	5
actin cytoskeleton reorganization	-0.002	0.024	-10000	0	-10000	0	0
SRC	0.016	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	13	13
PI3K	-0.002	0.031	-10000	0	-0.49	2	2
apoptosis	-0.06	0.096	0.43	12	-10000	0	12
T-DHT/AR/PELP1	-0.023	0.1	-10000	0	-0.49	24	24
HRAS/GDP	-0.026	0.12	-10000	0	-0.53	25	25
CREB1	0.061	0.1	-10000	0	-0.47	12	12
RAC1-CDC42/GTP	-0.002	0.024	-10000	0	-10000	0	0
AR	-0.02	0.16	-10000	0	-0.75	24	24
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.035	0.094	-10000	0	-0.45	4	4
RAC1-CDC42/GDP	-0.024	0.11	-10000	0	-0.49	24	24
T-DHT/AR/PELP1/Src	-0.021	0.094	-10000	0	-0.44	24	24
MAP2K2	0.046	0.094	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.015	0.069	-10000	0	-0.63	1	1
GNAZ	0.011	0.059	-10000	0	-0.75	3	3
SHBG	-0.063	0.23	-10000	0	-0.75	52	52
Gi family/GNB1/GNG2/GDP	-0.008	0.045	-10000	0	-0.45	2	2
mol:T-DHT	0	0	-10000	0	-0.003	9	9
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.17	0.31	-10000	0	-0.68	137	137
Gi family/GTP	-0.014	0.059	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.031	0.002	-9999	-10000	0	0
SMARCC1	0.026	0.01	-9999	-10000	0	0
REL	0.009	0.059	-9999	-0.74	3	3
HDAC7	-0.096	0.085	-9999	-0.67	3	3
JUN	0.015	0.003	-9999	-10000	0	0
EP300	0.014	0.034	-9999	-0.75	1	1
KAT2B	0.014	0.034	-9999	-0.75	1	1
KAT5	0.016	0	-9999	-10000	0	0
MAPK14	0.001	0.047	-9999	-0.59	3	3
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.087	-9999	-0.72	3	3
MAP2K6	-0.003	0.06	-9999	-0.77	3	3
BRM/BAF57	0	0	-9999	-10000	0	0
MAP2K4	0.002	0.006	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.12	0.13	-9999	-1.3	4	4
NCOA2	0.003	0.095	-9999	-0.75	8	8
CEBPA	-0.002	0.12	-9999	-0.86	10	10
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.091	0.094	-9999	-0.55	2	2
NR0B1	-0.05	0.21	-9999	-0.86	32	32
EGR1	-0.001	0.11	-9999	-0.75	11	11
RXRs/9cRA	-0.004	0.048	-9999	-0.54	4	4
AR/RACK1/Src	-0.014	0.058	-9999	-0.58	2	2
AR/GR	0.002	0.084	-9999	-0.72	3	3
GNB2L1	0.014	0.039	-9999	-0.86	1	1
PKN1	0.015	0.003	-9999	-10000	0	0
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.004	0.012	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.018	0.082	-9999	-0.79	2	2
SRC	0.004	0.042	-9999	-10000	0	0
NR3C1	0.014	0.039	-9999	-0.86	1	1
KLK3	-0.054	0.19	-9999	-0.74	23	23
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.025	0.051	-9999	-0.59	3	3
TMPRSS2	-0.96	0.38	-9999	-1.1	437	437
RXRG	0.006	0.078	-9999	-0.86	4	4
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.016	0.001	-9999	-10000	0	0
RXRB	0.016	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.014	0.034	-9999	-0.75	1	1
KLK2	-0.021	0.13	-9999	-0.63	18	18
AR	-0.009	0.085	-9999	-0.55	4	4
SENP1	0.016	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.013	0.009	-9999	-10000	0	0
SRY	0.002	0.007	-9999	-10000	0	0
GATA2	-0.002	0.12	-9999	-0.75	12	12
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.17	0.35	-9999	-0.86	103	103
T-DHT/AR/RACK1/Src	-0.014	0.057	-9999	-0.6	2	2
positive regulation of transcription	-0.002	0.12	-9999	-0.75	12	12
DNAJA1	0.002	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.002	-9999	-10000	0	0
NCOA1	0.024	0.005	-9999	-10000	0	0
SPDEF	-0.18	0.36	-9999	-0.86	112	112
T-DHT/AR/TIF2	0.021	0.067	-9999	-0.75	2	2
T-DHT/AR/Hsp90	-0.026	0.049	-9999	-0.62	2	2
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.009	0.046	-9999	-0.5	3	3
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.014	0.008	-9999	-10000	0	0
POU2F1	0.005	0.015	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.064	0.14	-9999	-0.61	25	25
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.003	0.043	-9999	-0.56	3	3
AKT1	-0.053	0.2	-9999	-0.71	3	3
PTK2B	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.003	0.042	-9999	-0.83	1	1
CAV1	-0.047	0.23	-9999	-0.86	36	36
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.22	0.25	-9999	-1.2	1	1
endothelial cell proliferation	-0.039	0.19	-9999	-0.69	1	1
mol:Ca2+	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.21	0.24	-9999	-1.2	1	1
RP11-342D11.1	-0.17	0.26	-9999	-1.1	1	1
CDH5	0.014	0.039	-9999	-0.86	1	1
VEGFA homodimer	-0.23	0.26	-9999	-0.52	225	225
SHC1	0.014	0.039	-9999	-0.86	1	1
SHC2	0.007	0.082	-9999	-0.82	5	5
HRAS/GDP	-0.17	0.19	-9999	-0.83	2	2
SH2D2A	-0.26	0.41	-9999	-0.86	162	162
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.14	0.15	-9999	-0.78	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.39	0.34	-9999	-1	64	64
VEGFR1 homodimer	0.007	0.087	-9999	-0.86	5	5
SHC/GRB2/SOS1	-0.18	0.2	-9999	-1.1	1	1
GRB10	-0.16	0.26	-9999	-1.1	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.2	0.22	-9999	-1	2	2
HRAS	0.014	0.039	-9999	-0.86	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.084	0.094	-9999	-0.58	1	1
HIF1A	0.013	0.048	-9999	-0.75	2	2
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.21	0.23	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	-0.001	0.025	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.22	0.25	-9999	-1.2	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.061	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.051	0.18	-9999	-0.57	1	1
PIK3R1	0.014	0.034	-9999	-0.75	1	1
mol:IP3	-0.16	0.26	-9999	-1.1	1	1
HIF1A/ARNT	-0.002	0.035	-9999	-0.56	2	2
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.37	0.43	-9999	-0.86	225	225
VEGFC	0.014	0.039	-9999	-0.86	1	1
FAK1/Vinculin	-0.1	0.22	-9999	-1	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.21	0.24	-9999	-1.2	1	1
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	0.026	0.037	-9999	-0.72	1	1
mol:L-citrulline	-0.061	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.22	0.25	-9999	-1.2	1	1
VEGFR2/3 heterodimer	-0.003	0.042	-9999	-0.83	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.15	0.26	-9999	-0.84	2	2
VEGFR2 homodimer	0.043	0.05	-9999	-0.73	2	2
FLT1	0.007	0.087	-9999	-0.86	5	5
NEDD4	0.015	0.048	-9999	-0.74	2	2
MAPK3	-0.14	0.25	-9999	-0.76	2	2
MAPK1	-0.14	0.25	-9999	-0.76	2	2
VEGFA145/NRP2	-0.3	0.33	-9999	-0.66	230	230
VEGFR1/2 heterodimer	-0.008	0.07	-9999	-0.61	6	6
KDR	0.043	0.051	-9999	-0.73	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.21	0.23	-9999	-1.2	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.14	0.25	-9999	-1	1	1
PI3K	-0.16	0.18	-9999	-0.78	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.23	0.25	-9999	-1.2	1	1
FES	-0.16	0.27	-9999	-1	2	2
GAB1	-0.16	0.19	-9999	-0.8	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.22	0.25	-9999	-1.2	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.08	0.2	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.22	0.25	-9999	-1.2	1	1
PI3K/GAB1	-0.053	0.19	-9999	-0.64	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.2	0.22	-9999	-1.1	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.045	-9999	-0.77	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.16	0.27	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.38	0.33	-9999	-1	64	64
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.26	-9999	-1.1	1	1
CaM/Ca2+	-0.18	0.2	-9999	-1	1	1
MAP2K3	-0.14	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.21	0.23	-9999	-1.2	1	1
PLCG1	-0.16	0.27	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.21	0.24	-9999	-1.2	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.22	0.25	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.22	0.25	-9999	-1.2	1	1
cell migration	-0.05	0.2	-9999	-0.77	1	1
mol:PI-3-4-5-P3	-0.15	0.17	-9999	-0.7	6	6
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.19	0.21	-9999	-1	1	1
mol:NO	-0.061	0.19	-9999	-0.62	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.17	0.19	-9999	-0.82	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.21	0.23	-9999	-1.2	1	1
VHL	0.016	0	-9999	-10000	0	0
ITGB3	0.011	0.059	-9999	-0.75	3	3
NOS3	-0.071	0.2	-9999	-0.73	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.23	0.26	-9999	-1.1	3	3
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.14	0.25	-9999	-1	1	1
PRKCB	-0.14	0.25	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.21	0.24	-9999	-1.2	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.23	0.26	-9999	-1.1	5	5
VEGFA165/NRP2	-0.3	0.33	-9999	-0.66	230	230
MAPKKK cascade	-0.16	0.18	-9999	-0.8	2	2
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFC homodimer	0.014	0.039	-9999	-0.86	1	1
NCK1	0.014	0.034	-9999	-0.75	1	1
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.1	0.22	-9999	-1	1	1
MAP3K13	-0.16	0.27	-9999	-1.2	1	1
PDPK1	-0.071	0.2	-9999	-0.76	3	3

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.043	0.091	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.096	0.22	-9999	-0.58	83	83
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.007	0.085	-9999	-0.84	5	5
RhoA/GTP	-0.044	0.092	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.012	0.12	-9999	-10000	0	0
GNAZ	0.011	0.059	-9999	-0.75	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.13	0.32	-9999	-0.86	83	83
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.051	0.11	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
GNAI1	0.011	0.059	-9999	-0.75	3	3

×

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	-0.012	0.059	-9999	-10000	0	0
epithelial cell differentiation	-0.017	0.08	-9999	-10000	0	0
CYFIP2	0.004	0.095	-9999	-0.75	8	8
ENAH	0.078	0.066	-9999	-10000	0	0
EGFR	0	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.034	-9999	-0.75	1	1
MYO6	0.032	0.098	-9999	-0.78	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.059	-9999	-0.48	8	8
AQP5	-0.17	0.24	-9999	-0.53	155	155
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.084	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.017	0.12	-9999	-0.84	1	1
EGF	-0.67	0.23	-9999	-0.75	455	455
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.051	0.16	-9999	-0.84	7	7
cortical microtubule organization	-0.017	0.08	-9999	-10000	0	0
GO:0000145	0.034	0.08	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.081	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GDP	-0.014	0.063	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.035	-9999	-0.52	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.05	0.085	-9999	-0.58	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.034	0.085	-9999	-10000	0	0
ARF6/GTP	-0.002	0.032	-9999	-10000	0	0
CDH1	-0.016	0.15	-9999	-0.75	21	21
EGFR/EGFR/EGF/EGF	-0.35	0.15	-9999	-0.78	27	27
RhoA/GDP	-0.015	0.074	-9999	-10000	0	0
actin cytoskeleton organization	0.041	0.093	-9999	-0.72	2	2
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
IGF1	0.005	0.095	-9999	-0.86	6	6
DIAPH1	-0.011	0.087	-9999	-0.7	8	8
Wnt receptor signaling pathway	0.017	0.08	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.064	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.041	0.096	-9999	-0.75	2	2
EFNA1	0.014	0.039	-9999	-0.86	1	1
LPP	0.043	0.09	-9999	-0.8	1	1
Ephrin A1/EPHA2	-0.016	0.075	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.063	-9999	-10000	0	0
MGAT3	0.017	0.13	-9999	-0.87	1	1
HGF/MET	-0.037	0.13	-9999	-0.95	4	4
HGF	-0.021	0.17	-9999	-0.8	23	23
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.012	0.059	-9999	-10000	0	0
actin cable formation	0.099	0.071	-9999	-10000	0	0
KIAA1543	0.036	0.13	-9999	-0.86	6	6
KIFC3	0.033	0.087	-9999	-10000	0	0
NCK1	0.014	0.034	-9999	-0.75	1	1
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.033	0.094	-9999	-0.87	1	1
NCK1/GIT1	-0.001	0.025	-9999	-0.56	1	1
mol:GDP	-0.017	0.08	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.034	0.085	-9999	-10000	0	0
PIP5K1C	0.034	0.085	-9999	-10000	0	0
LIMA1	0.016	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
ROCK1	-0.012	0.055	-9999	-10000	0	0
adherens junction assembly	0.058	0.12	-9999	-0.79	7	7
IGF-1R heterotetramer/IGF1	-0.02	0.085	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.007	0.087	-9999	-0.86	5	5
PLEKHA7	0.031	0.1	-9999	-0.78	3	3
mol:GTP	-0.003	0.035	-9999	-0.52	1	1
establishment of epithelial cell apical/basal polarity	0.07	0.077	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.059	-9999	-10000	0	0
regulation of cell-cell adhesion	0.041	0.093	-9999	-0.72	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.012	0.059	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.031	0.12	-9999	-0.51	31	31
RGS9BP	-0.016	0.15	-9999	-0.75	21	21
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.013	0.086	-9999	-0.59	11	11
mol:ADP	0.011	0.044	-9999	-0.68	2	2
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	35	35
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.026	-9999	-0.58	1	1
GRK7	0.008	0.055	-9999	-0.86	2	2
CNGB3	-0.008	0.11	-9999	-0.86	8	8
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.12	-9999	-0.64	15	15
Cone PDE6	-0.032	0.12	-9999	-0.53	11	11
Cone Metarhodopsin II	-0.002	0.035	-9999	-0.55	2	2
Na + (4 Units)	-0.019	0.11	-9999	-0.64	15	15
GNAT2/GDP	-0.029	0.11	-9999	-0.47	11	11
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.044	-9999	-0.54	3	3
Cone Transducin	-0.033	0.13	-9999	-0.53	31	31
SLC24A2	-0.009	0.1	-9999	-0.86	7	7
GNB3/GNGT2	-0.041	0.16	-9999	-0.66	31	31
GNB3	-0.037	0.21	-9999	-0.86	30	30
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0	0.067	-9999	-0.86	3	3
ARR3	0.004	0.007	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.013	0.087	-9999	-0.59	11	11
mol:Pi	-0.034	0.13	-9999	-0.5	35	35
Cone CNG Channel	-0.013	0.085	-9999	-0.96	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.009	0.1	-9999	-0.86	7	7
RGS9	-0.007	0.14	-9999	-0.81	14	14
PDE6C	0.003	0.055	-9999	-0.86	2	2
GNGT2	0.014	0.039	-9999	-0.86	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.039	-9999	-0.86	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.012	0.052	-9999	-0.8	2	2
GNB1/GNG2	-0.055	0.11	-9999	-0.54	8	8
mol:DAG	0.009	0.13	-9999	-10000	0	0
PLCG1	0.008	0.13	-9999	-10000	0	0
YES1	-0.012	0.14	-9999	-0.56	8	8
FZD3	0.016	0	-9999	-10000	0	0
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.051	0.1	-9999	-0.5	7	7
MAP3K7	-0.094	0.22	-9999	-0.56	40	40
mol:Ca2+	0.009	0.13	-9999	-10000	0	0
mol:IP3	0.009	0.13	-9999	-10000	0	0
NLK	-0.007	0.009	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.11	0.24	-9999	-0.61	47	47
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.065	0.13	-9999	-0.6	8	8
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.012	0.14	-9999	-0.56	8	8
GO:0007205	0.01	0.13	-9999	-10000	0	0
WNT6	-0.014	0.16	-9999	-0.86	17	17
WNT4	-0.071	0.24	-9999	-0.75	57	57
NFAT1/CK1 alpha	-0.049	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.059	-9999	-0.75	3	3
WNT11	-0.041	0.2	-9999	-0.76	37	37
CDC42	-0.001	0.14	-9999	-0.53	8	8

×

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ITGA4	-0.01	0.15	-9999	-0.86	15	15
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	15	15
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	15	15

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.007	0.085	-9999	-0.84	5	5
CDC42/GTP	-0.016	0.06	-9999	-10000	0	0
PLCG1	0.035	0.076	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.016	0.059	-9999	-10000	0	0
S1PR5	-0.13	0.32	-9999	-0.86	83	83
S1PR4	-0.026	0.19	-9999	-0.86	24	24
MAPK3	0.035	0.076	-9999	-10000	0	0
MAPK1	0.035	0.076	-9999	-10000	0	0
S1P/S1P5/Gi	-0.051	0.11	-9999	-10000	0	0
GNAI1	0.011	0.059	-9999	-0.75	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.096	0.22	-9999	-0.58	83	83
RHOA	0.018	0.11	-9999	-0.49	24	24
S1P/S1P4/Gi	-0.019	0.068	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.059	-9999	-0.75	3	3
S1P/S1P4/G12/G13	-0.025	0.11	-9999	-0.53	24	24
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	-0.28	0.37	-9999	-0.75	196	196
HRAS	0.014	0.039	-9999	-0.86	1	1
EGFR	0	0.11	-9999	-0.85	9	9
AKT	0.035	0.03	-9999	-10000	0	0
FOXO3	0.016	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
FOXO4	0.016	0	-9999	-10000	0	0
MET	0.007	0.087	-9999	-0.86	5	5
PIK3CA	0.014	0.034	-9999	-0.75	1	1
PIK3CB	0.016	0	-9999	-10000	0	0
NRAS	0.016	0	-9999	-10000	0	0
PIK3CG	0.011	0.067	-9999	-0.86	3	3
PIK3R3	0.016	0	-9999	-10000	0	0
PIK3R2	0.016	0	-9999	-10000	0	0
NF1	0.016	0	-9999	-10000	0	0
RAS	-0.042	0.098	-9999	-0.38	5	5
ERBB2	0.013	0.048	-9999	-0.75	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.023	0.092	-9999	-0.29	6	6
PIK3R1	0.014	0.034	-9999	-0.75	1	1
KRAS	0.016	0	-9999	-10000	0	0
FOXO	0.041	0.034	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.012	0.036	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.035	0.095	-9999	-0.48	6	6
JUN	0.027	0.11	-9999	-0.53	6	6
HRAS	0.014	0.039	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.052	0.16	-9999	-0.7	11	11
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.052	0.16	-9999	-0.7	11	11
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.04	0.13	-9999	-0.47	43	43
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.046	0.14	-9999	-0.67	9	9
GRB7	0.005	0.089	-9999	-0.75	7	7
RET51/GFRalpha1/GDNF	-0.052	0.16	-9999	-0.7	11	11
MAPKKK cascade	-0.041	0.12	-9999	-0.71	6	6
BCAR1	0.014	0.034	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.038	0.13	-9999	-0.46	42	42
lamellipodium assembly	-0.033	0.09	-9999	-0.44	6	6
RET51/GFRalpha1/GDNF/SHC	-0.053	0.16	-9999	-0.69	12	12
PIK3CA	0.014	0.034	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/SHC	-0.037	0.12	-9999	-0.46	40	40
RET9/GFRalpha1/GDNF/Shank3	-0.036	0.12	-9999	-0.46	39	39
MAPK3	0.006	0.15	-9999	-0.77	5	5
DOK1	0.016	0	-9999	-10000	0	0
DOK6	-0.002	0.12	-9999	-0.75	12	12
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.042	0.13	-9999	-0.73	5	5
DOK5	-0.006	0.13	-9999	-0.76	14	14
GFRA1	-0.039	0.2	-9999	-0.76	36	36
MAPK8	0.017	0.11	-9999	-0.57	6	6
HRAS/GTP	-0.048	0.14	-9999	-0.84	6	6
tube development	-0.033	0.11	-9999	-0.5	6	6
MAPK1	0.006	0.15	-9999	-0.77	5	5
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.023	0.08	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.009	0.078	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.058	0.17	-9999	-0.87	12	12
SHC1	0.014	0.039	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.052	0.16	-9999	-0.7	11	11
RET51/GFRalpha1/GDNF/Dok5	-0.064	0.19	-9999	-0.8	18	18
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.03	-9999	-0.68	1	1
CREB1	-0.031	0.097	-9999	-0.54	5	5
PIK3R1	0.014	0.034	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.024	0.081	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.057	0.18	-9999	-0.8	14	14
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.014	0.15	-9999	-0.76	19	19
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.027	0.11	-9999	-0.52	6	6
RET9/GFRalpha1/GDNF/FRS2	-0.036	0.12	-9999	-0.46	39	39
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.034	-9999	-0.75	1	1
NCK1	0.014	0.034	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.024	0.082	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.034	0.1	-9999	-0.6	5	5
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.035	0.11	-9999	-0.61	6	6
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.036	0.11	-9999	-0.77	5	5
PI3K	-0.05	0.14	-9999	-0.74	6	6
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.033	0.11	-9999	-0.5	6	6
GRB10	0.016	0	-9999	-10000	0	0
activation of MAPKK activity	-0.03	0.092	-9999	-0.53	5	5
RET51/GFRalpha1/GDNF/FRS2	-0.052	0.16	-9999	-0.7	11	11
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.011	0.059	-9999	-0.75	3	3
IRS2	0.002	0.11	-9999	-0.86	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.036	0.11	-9999	-0.77	5	5
RET51/GFRalpha1/GDNF/PKC alpha	-0.052	0.16	-9999	-0.7	11	11
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.001	0.067	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.054	0.16	-9999	-0.7	11	11
Rac1/GTP	-0.039	0.11	-9999	-0.54	6	6
RET9/GFRalpha1/GDNF	-0.039	0.14	-9999	-0.51	39	39
GFRalpha1/GDNF	-0.045	0.16	-9999	-0.59	39	39

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.075	0.074	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.16	0.28	-9999	-0.67	119	119
NFKBIA	0.063	0.021	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.014	0.039	-9999	-0.86	1	1
IKBKG	-0.047	0.084	-9999	-10000	0	0
IKK complex/A20	-0.041	0.08	-9999	-0.59	2	2
NEMO/A20/RIP2	0.014	0.039	-9999	-0.86	1	1
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	-0.043	0.077	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.034	0.062	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.19	0.37	-9999	-0.86	119	119
NFKB1	0.019	0.034	-9999	-0.74	1	1
RELA	0.02	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0.034	-9999	-0.75	1	1
TNF/TNFR1A	-0.01	0.077	-9999	-0.61	8	8
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
NF kappa B1 p50/RelA	-0.001	0.02	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.063	0.021	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	-0.038	0.07	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.035	0.064	-9999	-10000	0	0

×

Signaling events mediated by PRL

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.004	0.1	-10000	0	-0.86	7	7
mol:Halofuginone	0.007	0.001	-10000	0	-10000	0	0
ITGA1	0.016	0	-10000	0	-10000	0	0
CDKN1A	0.04	0.035	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.021	0.12	-10000	0	-0.66	16	16
mol:Ca2+	-0.017	0.16	0.4	16	-0.65	23	39
AGT	-0.022	0.18	-10000	0	-0.82	23	23
CCNA2	-0.058	0.23	-10000	0	-0.88	6	6
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.02	0.085	-10000	0	-0.55	11	11
CDK2/Cyclin E1	-0.01	0.058	-10000	0	-0.47	7	7
MAPK3	0.009	0.12	-10000	0	-0.66	16	16
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.12	-10000	0	-0.66	16	16
PTP4A1	0.041	0.068	-10000	0	-10000	0	0
PTP4A3	-0.012	0.15	-10000	0	-0.86	16	16
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.009	0.12	-10000	0	-0.66	16	16
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.031	0.059	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.002	0.035	-10000	0	-0.56	2	2
PRL-1/ATF-5	0.042	0.075	-10000	0	-10000	0	0
RABGGTA	0.013	0.048	-10000	0	-0.75	2	2
BCAR1	0.012	0.076	0.4	16	-0.58	1	17
RHOC	0.031	0.059	-10000	0	-10000	0	0
RHOA	0.031	0.059	-10000	0	-10000	0	0
cell motility	0.037	0.061	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.046	0.063	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.021	0.12	-10000	0	-0.66	16	16
ROCK1	0.037	0.062	-10000	0	-10000	0	0
RABGGTB	0.016	0	-10000	0	-10000	0	0
CDK2	0.016	0	-10000	0	-10000	0	0
mitosis	0.041	0.068	-10000	0	-10000	0	0
ATF5	0.011	0.067	-10000	0	-0.86	3	3

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.006	0.087	0.78	6	-10000	0	6
PI3K Class IB/PDE3B	0.006	0.087	-10000	0	-0.78	6	6
PDE3B	0.006	0.087	-10000	0	-0.79	6	6

×

p38 MAPK signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.014	0.034	-10000	0	-0.75	1	1
MAP2K3	0.038	0.044	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.049	0.045	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.003	0.13	-10000	0	-0.85	11	11
TXN	0.011	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
GADD45A	0.016	0	-10000	0	-10000	0	0
GADD45B	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
MAP3K6	0.014	0.034	-10000	0	-0.75	1	1
MAP3K7	0.016	0	-10000	0	-10000	0	0
MAP3K4	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.001	0.025	-10000	0	-0.56	1	1
TAK1/TAB family	0	0.009	0.2	1	-10000	0	1
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.004	0.014	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.1	0.28	-10000	0	-0.76	76	76
CCM2	0.016	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.075	0.18	-10000	0	-0.5	76	76
MAPK11	0.014	0.039	-10000	0	-0.86	1	1
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.067	0.16	-10000	0	-0.45	76	76
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	0.017	0.051	-10000	0	-0.41	7	7
TAOK2	0.022	0.019	-10000	0	-0.41	1	1
TAOK3	0.022	0.019	-10000	0	-0.41	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.016	0	-10000	0	-10000	0	0
MAP3K10	0.014	0.034	-10000	0	-0.75	1	1
MAP3K3	0.016	0	-10000	0	-10000	0	0
TRX/ASK1	0	0	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.011	0.071	-10000	0	-0.5	10	10

×

ErbB2/ErbB3 signaling events

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
USP8	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.075	-10000	0	-0.72	3	3
NFATC4	0.047	0.078	-10000	0	-0.54	2	2
ERBB2IP	0.008	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.016	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.018	0.078	-10000	0	-0.64	1	1
JUN	0.036	0.079	-10000	0	-0.41	2	2
HRAS	0.013	0.039	-10000	0	-0.86	1	1
DOCK7	0.019	0.092	-10000	0	-0.62	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.023	0.1	-10000	0	-0.87	2	2
AKT1	0.016	0.002	-10000	0	-10000	0	0
BAD	0.026	0.036	-10000	0	-0.54	2	2
MAPK10	-0.011	0.045	-10000	0	-0.39	1	1
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.019	0.085	-10000	0	-0.72	1	1
RAF1	0.038	0.096	-10000	0	-0.68	3	3
ErbB2/ErbB3/neuregulin 2	-0.02	0.098	-10000	0	-0.49	21	21
STAT3	0	0.002	-10000	0	-10000	0	0
cell migration	0.059	0.056	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.093	0.26	-10000	0	-0.6	9	9
FOS	-0.04	0.19	-10000	0	-0.48	15	15
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.018	0.078	-10000	0	-0.64	1	1
MAPK3	-0.061	0.21	-10000	0	-0.56	8	8
MAPK1	-0.061	0.21	-10000	0	-0.56	8	8
JAK2	0.019	0.089	-10000	0	-0.6	1	1
NF2	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.005	0.091	-10000	0	-0.82	2	2
NRG1	-0.015	0.13	-10000	0	-0.75	16	16
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.024	0.083	-10000	0	-0.44	2	2
MAPK9	-0.008	0.037	-10000	0	-10000	0	0
ERBB2	-0.002	0.036	-10000	0	-0.58	2	2
ERBB3	-0.005	0.1	-10000	0	-0.75	9	9
SHC1	0.007	0.039	-10000	0	-0.86	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.002	0.023	0.37	1	-10000	0	1
STAT3 (dimer)	0	0.002	-10000	0	-10000	0	0
RNF41	0.038	0.005	-10000	0	-10000	0	0
FRAP1	0.014	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.012	0.053	-10000	0	-0.41	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.031	-10000	0	-0.49	2	2
CHRNA1	-0.14	0.28	-10000	0	-0.45	224	224
myelination	0.05	0.075	-10000	0	-0.49	2	2
PPP3CB	0.019	0.083	-10000	0	-0.55	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.015	0.07	-10000	0	-0.72	2	2
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
mol:GDP	0.006	0.09	-10000	0	-0.82	2	2
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.044	0.098	-10000	0	-0.7	2	2
SRC	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.019	0.088	-10000	0	-0.6	1	1
MAP2K1	-0.044	0.18	-10000	0	-0.57	8	8
heart morphogenesis	-0.018	0.078	-10000	0	-0.64	1	1
RAS family/GDP	-0.015	0.074	-10000	0	-0.72	3	3
GRB2	0.009	0.008	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.02	0.027	-10000	0	-0.24	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.016	0.002	-10000	0	-10000	0	0
nervous system development	-0.018	0.078	-10000	0	-0.64	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.006	0.035	-10000	0	-10000	0	0
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.064	0.089	0.32	32	-0.36	1	33
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.031	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	-0.067	0.25	-10000	0	-0.86	46	46
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.043	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.059	-10000	0	-0.75	3	3
TRIP10	0.016	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.032	0.084	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	0.066	0.093	0.33	32	-0.4	1	33
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.034	0	-10000	0	-10000	0	0
SFN	-0.086	0.28	-10000	0	-0.83	61	61
LNPEP	0.014	0.034	-10000	0	-0.75	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.014	0.034	-10000	0	-0.75	1	1
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.025	0.044	0.66	2	-10000	0	2
CDKN1A	-0.003	0.041	-10000	0	-0.65	2	2
KAT2B	0.014	0.034	-10000	0	-0.75	1	1
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0.001	0.023	0.53	1	-10000	0	1
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.03	0.016	-10000	0	-0.34	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.003	0.12	-10000	0	-0.86	9	9
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.017	0.16	-10000	0	-0.66	28	28
PPARGC1A	-0.06	0.23	-10000	0	-0.75	50	50
FHL2	0.008	0.078	-10000	0	-0.77	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.008	-10000	0	-10000	0	0
HIST2H4A	0.025	0.044	-10000	0	-0.67	2	2
SIRT1/FOXO3a	0.001	0.016	0.32	1	-10000	0	1
SIRT1	0.001	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.001	0.019	-10000	0	-10000	0	0
apoptosis	-0.001	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.048	0.15	-10000	0	-0.49	50	50
p53/SIRT1	0.001	0.024	0.38	2	-10000	0	2
SIRT1/FOXO4	0	0.015	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.004	0.046	-10000	0	-0.53	1	1
HIST1H1E	0.029	0.022	-10000	0	-0.32	2	2
SIRT1/p300	-0.001	0.026	-10000	0	-0.56	1	1
muscle cell differentiation	0.031	0.13	0.57	28	-10000	0	28
TP53	0.001	0.011	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.008	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.011	0.088	-10000	0	-0.67	9	9
ACSS2	0.028	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.031	0.13	-10000	0	-0.57	28	28

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.059	-9999	-0.75	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.03	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.087	0.22	-9999	-0.62	71	71
IL1A	-0.007	0.13	-9999	-0.86	12	12
IL1B	0.023	0.074	-9999	-0.65	6	6
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-10000	0	0
IL1R2	-0.08	0.26	-9999	-0.79	60	60
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.004	0.025	-9999	-10000	0	0
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.016	0.001	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.041	0.046	-9999	-10000	0	0
JUN	0.061	0.03	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.01	0.07	-9999	-0.78	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.016	0.09	-9999	-0.53	1	1
PIK3R1	0.014	0.034	-9999	-0.75	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.015	0.084	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	-0.01	0.07	-9999	-0.52	8	8
NFKB1	0.014	0.034	-9999	-0.75	1	1
MAPK8	0.052	0.031	-9999	-10000	0	0
IRAK1	0.031	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.022	0.12	-9999	-0.66	17	17
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.035	-9999	-0.56	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.032	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.01	0.07	-9999	-0.52	8	8
IL1 beta/IL1R2	-0.067	0.18	-9999	-0.52	66	66
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.01	0.071	-9999	-1	1	1
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.009	0.061	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.009	0.048	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.018	0.1	-9999	-0.57	15	15
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-9999	-10000	0	0
IL1RAP	0.009	0.075	-9999	-0.83	4	4
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.007	0.049	-9999	-10000	0	0
CASP1	0.016	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.093	0.23	-9999	-0.63	75	75
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.009	0.065	-9999	-10000	0	0
TMEM189-UBE2V1	0.007	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.006	0.032	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
IL1RN	-0.014	0.16	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.043	0.033	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0	0.11	-10000	0	-0.77	10	10
EFNB1	0.017	0.097	-10000	0	-0.66	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.096	-10000	0	-0.75	3	3
Ephrin B2/EPHB1-2	-0.012	0.082	-10000	0	-0.54	11	11
neuron projection morphogenesis	-0.018	0.092	-10000	0	-0.71	3	3
Ephrin B1/EPHB1-2/Tiam1	-0.021	0.1	-10000	0	-0.81	3	3
DNM1	-0.002	0.12	-10000	0	-0.86	10	10
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.022	0.094	-10000	0	-0.67	9	9
YES1	-0.015	0.12	-10000	0	-0.9	9	9
Ephrin B1/EPHB1-2/NCK2	-0.02	0.1	-10000	0	-0.81	2	2
PI3K	-0.012	0.099	-10000	0	-0.7	10	10
mol:GDP	-0.021	0.1	-10000	0	-0.8	3	3
ITGA2B	-0.015	0.16	-10000	0	-0.86	18	18
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.015	0.12	-10000	0	-0.9	9	9
MAP3K7	-0.013	0.095	-10000	0	-0.72	9	9
FGR	-0.016	0.12	-10000	0	-0.89	9	9
TIAM1	0.014	0.034	-10000	0	-0.75	1	1
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	0.018	0.14	-10000	0	-0.69	11	11
LYN	-0.015	0.12	-10000	0	-0.9	9	9
Ephrin B1/EPHB1-2/Src Family Kinases	-0.016	0.11	-10000	0	-0.84	9	9
Ephrin B1/EPHB1-2	-0.016	0.1	-10000	0	-0.78	9	9
SRC	-0.015	0.12	-10000	0	-0.89	9	9
ITGB3	0.011	0.059	-10000	0	-0.75	3	3
EPHB1	0.011	0.062	-10000	0	-0.79	3	3
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.027	0.13	-10000	0	-0.64	21	21
BLK	-0.023	0.12	-10000	0	-0.89	9	9
HCK	-0.022	0.13	-10000	0	-0.94	9	9
regulation of stress fiber formation	0.02	0.098	0.8	2	-10000	0	2
MAPK8	0.032	0.09	-10000	0	-0.63	9	9
Ephrin B1/EPHB1-2/RGS3	-0.02	0.1	-10000	0	-0.81	2	2
endothelial cell migration	-0.009	0.082	-10000	0	-0.61	9	9
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.011	0.11	-10000	0	-0.85	9	9
regulation of focal adhesion formation	0.02	0.098	0.8	2	-10000	0	2
chemotaxis	0.02	0.098	0.8	2	-10000	0	2
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
Rac1/GTP	-0.019	0.095	-10000	0	-0.74	3	3
angiogenesis	-0.016	0.1	-10000	0	-0.78	9	9
LCK	-0.021	0.12	-10000	0	-0.91	9	9

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.036	0.053	-9999	-0.5	5	5
SNTA1	0.012	0.052	-9999	-0.8	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.037	0.046	-9999	-0.48	4	4
MAPK12	0.028	0.086	-9999	-0.49	13	13
CCND1	0.014	0.07	-9999	-0.3	19	19
p38 gamma/SNTA1	0.032	0.09	-9999	-0.51	11	11
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.016	0	-9999	-10000	0	0
G2/M transition checkpoint	0.028	0.085	-9999	-0.49	13	13
MAP2K6	0.03	0.042	-9999	-0.47	3	3
MAPT	0.032	0.069	-9999	-0.5	6	6
MAPK13	0.026	0.052	-9999	-0.56	4	4
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.022	0.018	-9999	-0.39	1	1

×

Syndecan-3-mediated signaling events

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
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.069	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.011	0.073	-9999	-0.49	11	11
POMC	0.012	0.052	-9999	-0.8	2	2
EGFR	0	0.11	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.009	0.066	-9999	-0.49	8	8
AGRP	0.007	0.048	-9999	-0.75	2	2
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.008	0.13	-9999	-0.86	11	11
long-term memory	-0.001	0.016	-9999	-10000	0	0
Syndecan-3/IL8	-0.032	0.12	-9999	-0.49	27	27
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.001	0.019	-9999	-0.42	1	1
MC4R	-0.009	0.11	-9999	-0.86	8	8
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.75	18	18
FGFR/FGF/Syndecan-3	-0.001	0.019	-9999	-0.43	1	1
neuron projection morphogenesis	-0.022	0.088	-9999	-10000	0	0
Syndecan-3/AgRP	-0.002	0.031	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.01	0.065	-9999	-0.47	1	1
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.019	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.031	0.12	-9999	-0.47	33	33
IL8	-0.04	0.21	-9999	-0.84	33	33
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.018	-9999	-0.41	1	1
alpha-MSH/MC4R	-0.013	0.091	-9999	-0.66	10	10
Gamma Secretase	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.021	0.1	-9999	-0.51	21	21
KLHL20	-0.013	0.046	-9999	-0.35	2	2
CYFIP2	0.004	0.095	-9999	-0.75	8	8
Rac1/GDP	0.067	0.077	-9999	-10000	0	0
ENAH	-0.021	0.1	-9999	-0.51	21	21
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
CDC42/GTP	-0.01	0.047	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.036	-9999	-0.22	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.085	-9999	-10000	0	0
RAPGEF1	0.053	0.1	-9999	-10000	0	0
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.022	0.11	-9999	-0.54	21	21
CRK	0.042	0.11	-9999	-0.47	21	21
E-cadherin/gamma catenin/alpha catenin	-0.023	0.1	-9999	-0.5	23	23
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	-0.021	0.1	-9999	-0.51	21	21
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.035	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.001	0.019	-9999	-0.44	1	1
PI3K	-0.01	0.045	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.026	0.12	-9999	-0.58	23	23
TIAM1	0.014	0.034	-9999	-0.75	1	1
E-cadherin(dimer)/Ca2+	-0.017	0.081	-9999	-10000	0	0
AKT1	-0.005	0.025	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
CDH1	-0.016	0.15	-9999	-0.75	21	21
RhoA/GDP	0.067	0.076	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.034	-9999	-0.24	2	2
CDC42/GDP	0.067	0.076	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.015	0.069	-9999	-0.47	2	2
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.018	0.085	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.083	-9999	-0.42	21	21
mol:GDP	0.063	0.087	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.059	-9999	-0.75	3	3
p120 catenin/RhoA/GDP	-0.013	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.036	0.063	-9999	-0.26	19	19
NME1	0.016	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.021	0.1	-9999	-0.51	21	21
regulation of cell-cell adhesion	-0.009	0.042	-9999	-10000	0	0
WASF2	-0.005	0.018	-9999	-10000	0	0
Rap1/GTP	-0.011	0.055	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.019	0.088	-9999	-0.81	1	1
CCND1	-0.016	0.065	-9999	-0.33	19	19
VAV2	0.049	0.1	-9999	-0.5	1	1
RAP1/GDP	-0.011	0.057	-9999	-10000	0	0
adherens junction assembly	0.032	0.11	-9999	-0.5	21	21
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.018	0.083	-9999	-0.78	1	1
E-cadherin/beta catenin	-0.019	0.091	-9999	-0.46	21	21
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.021	0.1	-9999	-0.51	21	21
PIK3CA	0.014	0.034	-9999	-0.75	1	1
Rac1/GTP	-0.02	0.071	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.02	0.095	-9999	-0.48	21	21
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.023	0.11	-9999	-0.55	21	21

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.007	0.066	-9999	-0.66	5	5
CRKL	0.04	0.066	-9999	-0.46	2	2
mol:PIP3	-0.03	0.003	-9999	-10000	0	0
AKT1	0	0.02	-9999	-0.45	1	1
PTK2B	0.016	0	-9999	-10000	0	0
RAPGEF1	0.049	0.063	-9999	-0.43	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
HGF/MET/SHIP2	-0.029	0.13	-9999	-0.57	26	26
MAP3K5	-0.022	0.12	-9999	-0.41	1	1
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.027	0.12	-9999	-0.61	15	15
AP1	-0.015	0.083	-9999	-0.52	13	13
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.039	-9999	-0.86	1	1
apoptosis	0.003	0.11	-9999	-0.7	12	12
STAT3 (dimer)	0.041	0.079	-9999	-0.53	3	3
GAB1/CRKL/SHP2/PI3K	-0.011	0.055	-9999	-0.59	2	2
INPP5D	0.009	0.078	-9999	-0.86	4	4
CBL/CRK	0.046	0.069	-9999	-0.51	3	3
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	0	0.03	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.009	0.039	-9999	-0.34	2	2
PAK1	0.01	0.019	-9999	-10000	0	0
HGF/MET/RANBP10	-0.029	0.13	-9999	-0.57	26	26
HRAS	0.031	0.099	-9999	-0.71	3	3
DOCK1	0.048	0.069	-9999	-0.51	3	3
GAB1	0.03	0.069	-9999	-0.44	3	3
CRK	0.04	0.066	-9999	-0.46	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.023	0.1	-9999	-0.54	14	14
JUN	0.016	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.013	0.061	-9999	-0.4	5	5
PIK3R1	0.014	0.034	-9999	-0.75	1	1
cell morphogenesis	0.079	0.085	-9999	-0.66	2	2
GRB2/SHC	-0.012	0.058	-9999	-0.53	3	3
FOS	-0.004	0.12	-9999	-0.76	13	13
GLMN	0	0	-9999	-10000	0	0
cell motility	0	0.03	-9999	-0.29	5	5
HGF/MET/MUC20	-0.03	0.13	-9999	-0.58	26	26
cell migration	-0.012	0.057	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.014	0.034	-9999	-0.75	1	1
MET/RANBP10	-0.007	0.066	-9999	-0.66	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.016	0.073	-9999	-0.58	3	3
MET/MUC20	-0.007	0.067	-9999	-0.68	5	5
RAP1B	0.057	0.06	-9999	-10000	0	0
RAP1A	0.057	0.06	-9999	-10000	0	0
HGF/MET/RANBP9	-0.029	0.13	-9999	-0.57	26	26
RAF1	0.04	0.094	-9999	-0.66	3	3
STAT3	-0.015	0.067	-9999	-0.54	3	3
cell proliferation	0.054	0.1	-9999	-0.62	4	4
RPS6KB1	-0.004	0.02	-9999	-10000	0	0
MAPK3	-0.006	0.027	-9999	-0.27	5	5
MAPK1	-0.006	0.027	-9999	-0.27	5	5
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.014	0.094	-9999	-10000	0	0
SRC	0.042	0.079	-9999	-0.54	3	3
PI3K	-0.013	0.062	-9999	-0.54	4	4
MET/Glomulin	0.009	0.062	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.05	0.088	-9999	-0.59	3	3
MET	0.007	0.087	-9999	-0.86	5	5
MAP4K1	-0.035	0.12	-9999	-0.4	12	12
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.049	0.09	-9999	-0.59	3	3
BAD	0.008	0.045	-9999	-0.91	1	1
MAP2K4	-0.01	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.012	0.057	-9999	-0.56	2	2
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.012	0.054	-9999	-0.49	2	2
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.021	0.17	-9999	-0.8	23	23
RASA1	0.014	0.034	-9999	-0.75	1	1
NCK1	0.014	0.034	-9999	-0.75	1	1
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.013	0.06	-9999	-0.53	3	3
PDPK1	-0.014	0.021	-9999	-0.49	1	1
HGF/MET/SHIP	-0.034	0.14	-9999	-0.59	29	29

×

Arf6 downstream 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.019	0.17	-10000	0	-0.71	26	26
regulation of axonogenesis	-0.033	0.035	-10000	0	-10000	0	0
myoblast fusion	0.016	0.07	0.32	26	-10000	0	26
mol:GTP	-0.01	0.043	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.041	0.45	1	-10000	0	1
ARF1/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GM1	0.007	0.035	-10000	0	-10000	0	0
mol:Choline	0.033	0.031	-10000	0	-10000	0	0
lamellipodium assembly	-0.017	0.073	-10000	0	-0.33	26	26
MAPK3	0.024	0.069	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.041	-10000	0	-0.45	1	1
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.071	-10000	0	-0.32	26	26
ARF1/GDP	0.02	0.07	-10000	0	-10000	0	0
ARF6	0.009	0.024	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.016	0.034	-10000	0	-0.74	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.024	0.069	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.013	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.025	-10000	0	-0.56	1	1
RhoA/GDP	-0.015	0.063	-10000	0	-10000	0	0
NME1	0.017	0.004	-10000	0	-10000	0	0
Rac1/GDP	-0.015	0.063	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.017	0.074	-10000	0	-0.33	26	26
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.01	0.043	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.043	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.016	0.071	-10000	0	-0.32	26	26
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.03	-10000	0	-0.46	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.021	0.035	-10000	0	-10000	0	0
RAB11FIP3	0.014	0.034	-10000	0	-0.75	1	1
tube morphogenesis	-0.017	0.073	-10000	0	-0.33	26	26
ruffle organization	0.033	0.035	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.043	-10000	0	-10000	0	0
PLD2	0.021	0.035	-10000	0	-10000	0	0
PIP5K1A	0.033	0.035	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.031	-10000	0	-10000	0	0
Rac1/GTP	-0.017	0.074	-10000	0	-0.33	26	26

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.012	-10000	0	-10000	0	0
DOCK1	0.014	0.034	-10000	0	-0.75	1	1
ITGA4	-0.01	0.15	-10000	0	-0.86	15	15
RAC1	0.016	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.02	0.11	-10000	0	-0.66	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.017	0.097	-10000	0	-0.57	15	15
alpha4/beta7 Integrin/Paxillin	-0.015	0.088	-10000	0	-0.52	15	15
lamellipodium assembly	-0.001	0.044	-10000	0	-0.77	1	1
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
PI3K	-0.002	0.035	-10000	0	-0.56	2	2
ARF6	0.016	0	-10000	0	-10000	0	0
TLN1	0.016	0	-10000	0	-10000	0	0
PXN	0.031	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
ARF6/GTP	-0.013	0.074	-10000	0	-10000	0	0
cell adhesion	-0.014	0.081	-10000	0	-10000	0	0
CRKL/CBL	-0.001	0.025	-10000	0	-0.56	1	1
alpha4/beta1 Integrin/Paxillin	-0.015	0.088	-10000	0	-0.52	15	15
ITGB1	0.016	0	-10000	0	-10000	0	0
ITGB7	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	0.002	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.027	0.11	-10000	0	-0.48	24	24
p130Cas/Crk/Dock1	-0.002	0.03	-10000	0	-0.48	2	2
VCAM1	-0.007	0.14	-10000	0	-0.82	14	14
alpha4/beta1 Integrin/Paxillin/Talin	-0.014	0.082	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.014	0.082	-10000	0	-0.48	15	15
BCAR1	0.014	0.034	-10000	0	-0.75	1	1
mol:GDP	0.014	0.081	0.48	15	-10000	0	15
CBL	0.014	0.034	-10000	0	-0.75	1	1
PRKACA	0.016	0	-10000	0	-10000	0	0
GIT1	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.014	0.082	-10000	0	-10000	0	0
Rac1/GTP	-0.001	0.051	-10000	0	-0.93	1	1

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.056	0.16	-10000	0	-0.5	57	57
cell-cell adhesion	0.013	0.072	0.63	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	-0.014	0.08	-10000	0	-0.81	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
SHC1	0.014	0.039	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.014	0.081	-10000	0	-0.5	14	14
Ephrin B1/EPHB1	-0.003	0.04	-10000	0	-0.52	3	3
HRAS/GDP	-0.008	0.052	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.013	0.072	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.036	0.085	-10000	0	-0.75	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.008	0.056	-10000	0	-10000	0	0
endothelial cell migration	-0.002	0.025	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.005	0.089	-10000	0	-0.75	7	7
PAK1	0.048	0.083	-10000	0	-0.76	1	1
HRAS	0.014	0.039	-10000	0	-0.86	1	1
RRAS	0.036	0.086	-10000	0	-0.77	1	1
DNM1	-0.002	0.12	-10000	0	-0.86	10	10
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.043	0.061	-10000	0	-10000	0	0
lamellipodium assembly	-0.013	0.072	-10000	0	-0.63	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.005	0.036	-10000	0	-10000	0	0
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
EPHB2	0	0.11	-10000	0	-0.77	10	10
EPHB3	-0.006	0.13	-10000	0	-0.76	14	14
EPHB1	0.011	0.062	-10000	0	-0.79	3	3
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.058	-10000	0	-10000	0	0
Ephrin B/EPHB2	-0.014	0.08	-10000	0	-0.6	3	3
Ephrin B/EPHB3	-0.017	0.09	-10000	0	-0.71	3	3
JNK cascade	0.041	0.084	-10000	0	-0.79	2	2
Ephrin B/EPHB1	-0.008	0.058	-10000	0	-0.5	1	1
RAP1/GDP	-0.002	0.051	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.005	0.089	-10000	0	-0.75	7	7
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.012	0.082	-10000	0	-0.54	11	11
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.015	0.08	-10000	0	-0.71	3	3
Rap1/GTP	-0.013	0.073	-10000	0	-0.64	3	3
axon guidance	-0.056	0.16	-10000	0	-0.49	57	57
MAPK3	0.065	0.04	-10000	0	-10000	0	0
MAPK1	0.065	0.04	-10000	0	-10000	0	0
Rac1/GDP	-0.002	0.054	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.011	0.058	-10000	0	-0.5	2	2
CDC42/GDP	-0.002	0.054	-10000	0	-10000	0	0
PI3K	-0.002	0.025	-10000	0	-10000	0	0
EFNA5	-0.056	0.22	-10000	0	-0.76	47	47
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.01	0.056	-10000	0	-0.61	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.014	0.076	-10000	0	-0.64	4	4
PTK2	0.002	0.017	-10000	0	-10000	0	0
MAP4K4	0.041	0.085	-10000	0	-0.8	2	2
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.011	0.058	-10000	0	-0.5	3	3
MAP2K1	0.057	0.042	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.012	0.083	-10000	0	-0.66	5	5
cell migration	0.067	0.047	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.036	0.087	-10000	0	-0.77	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.073	0.23	-10000	0	-0.79	3	3
HRAS/GTP	-0.015	0.085	-10000	0	-0.72	4	4
Ephrin B1/EPHB1-2	-0.012	0.082	-10000	0	-0.54	11	11
cell adhesion mediated by integrin	0.01	0.064	0.47	7	-10000	0	7
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.016	0.086	-10000	0	-0.75	3	3
RAC1-CDC42/GTP	-0.022	0.099	-10000	0	-0.78	5	5
RASA1	0.014	0.034	-10000	0	-0.75	1	1
RAC1-CDC42/GDP	-0.002	0.051	-10000	0	-10000	0	0
ruffle organization	0.07	0.088	-10000	0	-0.65	3	3
NCK1	0.014	0.034	-10000	0	-0.75	1	1
receptor internalization	0.036	0.11	-10000	0	-0.72	1	1
Ephrin B/EPHB2/KALRN	-0.014	0.078	-10000	0	-0.81	1	1
ROCK1	0.021	0.078	-10000	0	-0.44	14	14
RAS family/GDP	-0.011	0.058	-10000	0	-0.53	1	1
Rac1/GTP	-0.014	0.077	-10000	0	-0.69	3	3
Ephrin B/EPHB1/Src/Paxillin	-0.006	0.04	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.049	0.12	-9999	-0.68	5	5
MAP3K8	0.013	0.055	-9999	-0.86	2	2
FOS	0.041	0.11	-9999	-0.57	5	5
PRKCA	0.017	0.003	-9999	-10000	0	0
PTPN7	-0.037	0.21	-9999	-0.86	32	32
HRAS	0.014	0.039	-9999	-0.86	1	1
PRKCB	0.009	0.084	-9999	-0.82	5	5
NRAS	0.016	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.024	-9999	-0.53	1	1
MAPK3	0.029	0.085	-9999	-0.52	3	3
MAP2K1	0.055	0.056	-9999	-0.5	4	4
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.004	0.044	-9999	-0.48	3	3
mol:GTP	0	0.001	-9999	-0.006	12	12
MAPK1	0.029	0.085	-9999	-0.52	3	3
RAF1	-0.004	0.044	-9999	-0.46	4	4
KRAS	0.016	0.001	-9999	-10000	0	0

×

BARD1 signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.004	0.05	-10000	0	-0.56	4	4
ATM	0.014	0.034	-10000	0	-0.75	1	1
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.034	0.019	-10000	0	-0.4	1	1
protein ubiquitination	-0.01	0.073	-10000	0	-0.88	1	1
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.034	0.068	-10000	0	-0.51	1	1
FANCF	0.016	0	-10000	0	-10000	0	0
BRCA1	0.016	0	-10000	0	-10000	0	0
CCNE1	0.004	0.1	-10000	0	-0.86	7	7
CDK2/Cyclin E1	-0.009	0.078	-10000	0	-0.66	7	7
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.05	-10000	0	-0.56	4	4
FANCE	0.014	0.039	-10000	0	-0.86	1	1
FANCC	0.016	0	-10000	0	-10000	0	0
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.17	0.36	-10000	0	-0.86	107	107
DNA repair	0.043	0.14	-10000	0	-0.59	12	12
BRCA1/BARD1/ubiquitin	-0.004	0.05	-10000	0	-0.56	4	4
BARD1/DNA-PK	-0.003	0.038	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.05	0.56	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	-0.004	0.043	-10000	0	-0.78	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.042	-10000	0	-0.48	4	4
BRCA1/BARD1/P53	-0.003	0.038	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.004	0.042	-10000	0	-0.48	4	4
BRCA1/BACH1	0.016	0	-10000	0	-10000	0	0
BARD1	0.01	0.068	-10000	0	-0.75	4	4
PCNA	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.004	0.042	-10000	0	-0.48	4	4
BRCA1/BARD1/UbcH7	-0.004	0.042	-10000	0	-0.48	4	4
BRCA1/BARD1/RAD51/PCNA	-0.018	0.093	-10000	0	-0.52	14	14
BARD1/DNA-PK/P53	-0.003	0.035	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.05	-10000	0	-0.56	4	4
BRCA1/BARD1/CTIP	-0.005	0.054	-10000	0	-0.86	1	1
FA complex	-0.057	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.05	-10000	0	-0.56	4	4
RBBP8	0.029	0.047	-10000	0	-1	1	1
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.038	-10000	0	-10000	0	0
BRCA1/BARD1	-0.011	0.074	-10000	0	-0.9	1	1
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.005	0.051	-10000	0	-0.57	4	4
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.009	0.14	-10000	0	-0.86	14	14
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.05	-10000	0	-0.56	4	4
EWSR1	0.016	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.014	0.034	-10000	0	-0.75	1	1
ANTXR2	0.014	0.034	-10000	0	-0.75	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.006	-10000	0	-0.094	2	2
monocyte activation	0.006	0.086	-10000	0	-0.37	21	21
MAP2K2	-0.002	0.036	-10000	0	-0.8	1	1
MAP2K1	0	0.005	-10000	0	-10000	0	0
MAP2K7	0	0.005	-10000	0	-10000	0	0
MAP2K6	-0.003	0.034	-10000	0	-0.43	3	3
CYAA	0.02	0.028	-10000	0	-0.42	2	2
MAP2K4	0	0.005	-10000	0	-10000	0	0
IL1B	0.016	0.06	-10000	0	-0.49	6	6
Channel	-0.002	0.028	-10000	0	-0.45	2	2
NLRP1	-0.005	0.052	-10000	0	-0.52	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.006	0.094	2	-10000	0	2
MAPK3	0	0.005	-10000	0	-10000	0	0
MAPK1	0	0.005	-10000	0	-10000	0	0
PGR	-0.016	0.082	-10000	0	-0.44	18	18
PA/Cellular Receptors	-0.002	0.031	-10000	0	-0.49	2	2
apoptosis	0	0.006	-10000	0	-0.094	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.002	0.026	-10000	0	-0.42	2	2
macrophage activation	0.027	0.006	-10000	0	-10000	0	0
TNF	0.003	0.1	-10000	0	-0.8	8	8
VCAM1	-0.015	0.082	-10000	0	-0.37	21	21
platelet activation	0	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.022	0.01	-10000	0	-10000	0	0
IL18	0.015	0.067	-10000	0	-0.51	7	7
negative regulation of macrophage activation	0	0.006	-10000	0	-0.094	2	2
LEF	0	0.006	-10000	0	-0.094	2	2
CASP1	-0.003	0.024	-10000	0	-0.23	5	5
mol:cAMP	0	0.007	-10000	0	-10000	0	0
necrosis	0	0.006	-10000	0	-0.094	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.027	-10000	0	-0.43	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.01	0.067	-10000	0	-0.5	6	6
ER alpha/Gai/GDP/Gbeta gamma	0.054	0.055	-10000	0	-10000	0	0
AKT1	0.046	0.074	-10000	0	-0.82	3	3
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.041	0.074	-10000	0	-0.84	3	3
mol:Ca2+	-0.014	0.18	-10000	0	-0.68	11	11
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.007	0.066	-10000	0	-0.58	6	6
SHC1	0.014	0.039	-10000	0	-0.86	1	1
apoptosis	-0.046	0.071	0.78	3	-10000	0	3
RhoA/GTP	-0.004	0.038	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.007	0.046	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.068	0.045	0.54	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.012	0.079	-10000	0	-0.54	11	11
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.004	0.042	-10000	0	-0.47	4	4
pseudopodium formation	0.068	0.045	-10000	0	-0.54	1	1
E2/ER alpha (dimer)/PELP1	-0.004	0.046	-10000	0	-0.51	4	4
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.007	0.085	-10000	0	-0.84	5	5
HRAS	0.014	0.039	-10000	0	-0.86	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.063	0.062	-10000	0	-0.49	3	3
E2/ER beta (dimer)	-0.009	0.076	-10000	0	-0.65	7	7
mol:GDP	-0.009	0.061	-10000	0	-0.47	4	4
mol:NADP	0.063	0.062	-10000	0	-0.49	3	3
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
mol:IP3	-0.016	0.19	-10000	0	-0.73	11	11
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.023	0.098	-10000	0	-0.58	9	9
PLCB2	-0.067	0.16	-10000	0	-0.48	62	62
IGF1	0.005	0.095	-10000	0	-0.86	6	6
mol:L-citrulline	0.063	0.062	-10000	0	-0.49	3	3
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.048	-10000	0	-0.63	1	1
JNK cascade	-0.009	0.075	-10000	0	-0.64	7	7
BCAR1	0.014	0.034	-10000	0	-0.75	1	1
ESR2	0.004	0.099	-10000	0	-0.83	7	7
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.009	0.07	-10000	0	-0.78	4	4
Gq family/GDP/Gbeta gamma	-0.015	0.07	-10000	0	-0.51	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.052	0.033	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.007	0.046	-10000	0	-10000	0	0
GNAZ	0.011	0.059	-10000	0	-0.75	3	3
E2/ER alpha (dimer)	-0.005	0.053	-10000	0	-0.6	4	4
STRN	0.011	0.059	-10000	0	-0.75	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.016	0.073	-10000	0	-0.56	8	8
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.059	-10000	0	-0.75	3	3
HBEGF	-0.043	0.14	-10000	0	-0.51	6	6
cAMP biosynthetic process	-0.01	0.064	-10000	0	-0.44	11	11
SRC	0.063	0.053	-10000	0	-10000	0	0
PI3K	-0.002	0.035	-10000	0	-0.56	2	2
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.008	0.053	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.01	0.05	-10000	0	-10000	0	0
Gs family/GTP	-0.01	0.065	-10000	0	-0.45	11	11
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.024	-10000	0	-0.53	1	1
vasodilation	0.062	0.06	-10000	0	-0.47	3	3
mol:DAG	-0.016	0.19	-10000	0	-0.73	11	11
Gs family/GDP/Gbeta gamma	-0.007	0.048	-10000	0	-10000	0	0
MSN	0.07	0.049	-10000	0	-0.6	1	1
Gq family/GTP	-0.018	0.077	-10000	0	-0.46	10	10
mol:PI-3-4-5-P3	0.041	0.071	-10000	0	-0.8	3	3
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.062	0.06	0.47	3	-10000	0	3
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.009	0.056	-10000	0	-0.45	3	3
NOS3	0.063	0.064	-10000	0	-0.52	3	3
GNA11	0.013	0.048	-10000	0	-0.75	2	2
MAPKKK cascade	0.072	0.069	-10000	0	-0.59	4	4
E2/ER alpha (dimer)/PELP1/Src	-0.007	0.046	-10000	0	-0.48	3	3
ruffle organization	0.068	0.045	-10000	0	-0.54	1	1
ROCK2	-0.005	0.046	-10000	0	-0.68	1	1
GNA14	0.005	0.089	-10000	0	-0.75	7	7
GNA15	-0.009	0.14	-10000	0	-0.86	14	14
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.17	0.25	-10000	0	-0.66	8	8
MMP2	0.065	0.081	-10000	0	-0.66	3	3

×

E-cadherin signaling in keratinocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.057	0.053	-10000	0	-0.46	1	1
adherens junction organization	0.04	0.08	-10000	0	-0.53	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.061	-10000	0	-10000	0	0
FMN1	0.022	0.12	-10000	0	-0.67	2	2
mol:IP3	-0.008	0.041	-10000	0	-0.48	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.066	-10000	0	-0.71	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.053	0.058	-10000	0	-0.51	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.11	-10000	0	-0.53	21	21
CTNND1	0.016	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.075	-10000	0	-0.56	2	2
VASP	0.044	0.073	-10000	0	-0.67	1	1
ZYX	0.044	0.073	-10000	0	-0.67	1	1
JUB	0.042	0.081	-10000	0	-0.58	2	2
EGFR(dimer)	-0.021	0.083	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.022	0.1	-10000	0	-0.48	23	23
mol:PI-3-4-5-P3	-0.01	0.048	-10000	0	-0.54	1	1
PIK3CA	0.015	0.034	-10000	0	-0.75	1	1
PI3K	-0.01	0.049	-10000	0	-0.56	1	1
FYN	-0.24	0.13	-10000	0	-0.62	2	2
mol:Ca2+	-0.008	0.04	-10000	0	-0.47	1	1
JUP	-0.003	0.058	-10000	0	-0.74	3	3
PIK3R1	0.015	0.034	-10000	0	-0.75	1	1
mol:DAG	-0.008	0.041	-10000	0	-0.48	1	1
CDH1	-0.031	0.15	-10000	0	-0.75	21	21
RhoA/GDP	-0.014	0.061	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.044	0.072	-10000	0	-0.65	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	0	0.11	-10000	0	-0.85	9	9
CASR	-0.29	0.15	-10000	0	-0.54	17	17
RhoA/GTP	-0.007	0.035	-10000	0	-10000	0	0
AKT2	0.053	0.058	-10000	0	-0.51	1	1
actin cable formation	0.032	0.12	-10000	0	-0.64	2	2
apoptosis	0.009	0.044	0.49	1	-10000	0	1
CTNNA1	0.016	0.004	-10000	0	-10000	0	0
mol:GDP	-0.015	0.067	-10000	0	-10000	0	0
PIP5K1A	0.044	0.077	-10000	0	-0.58	2	2
PLCG1	-0.008	0.042	-10000	0	-0.49	1	1
Rac1/GTP	-0.019	0.075	-10000	0	-0.6	1	1
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.009	0.059	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.057	-9999	-0.68	1	1
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.049	-9999	-0.55	4	4
AP1	-0.017	0.084	-9999	-0.71	4	4
ILK	0.062	0.057	-9999	-10000	0	0
bone resorption	-0.024	0.098	-9999	-0.76	2	2
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.007	0.049	-9999	-10000	0	0
ITGAV	0.022	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.03	0.14	-9999	-0.66	23	23
alphaV/beta3 Integrin/Osteopontin	-0.007	0.054	-9999	-0.48	3	3
MAP3K1	0.063	0.058	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.074	0.076	-9999	-10000	0	0
MAPK1	0.074	0.076	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0.034	-9999	-0.75	1	1
MAPK8	0.076	0.057	-9999	-10000	0	0
ITGB3	0.018	0.059	-9999	-0.74	3	3
NFKBIA	0.087	0.077	-9999	-10000	0	0
FOS	-0.003	0.12	-9999	-0.76	13	13
CD44	-0.021	0.18	-9999	-0.86	21	21
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.086	0.17	-9999	-1.1	9	9
NF kappa B1 p50/RelA	-0.011	0.058	-9999	-0.64	1	1
BCAR1	0.014	0.034	-9999	-0.75	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.003	0.042	-9999	-0.55	3	3
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.059	0.064	-9999	-10000	0	0
VAV3	0.057	0.098	-9999	-0.78	1	1
MAP3K14	0.061	0.077	-9999	-0.5	4	4
ROCK2	0.013	0.048	-9999	-0.75	2	2
SPP1	0.016	0.067	-9999	-0.74	4	4
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.015	0.074	-9999	-0.71	1	1
MMP2	0.099	0.12	-9999	-0.76	6	6

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.021	-9999	-0.48	1	1
forebrain development	0.054	0.094	-9999	-0.5	2	2
GNAO1	0.007	0.085	-9999	-0.84	5	5
SMO/beta Arrestin2	-0.002	0.039	-9999	-0.61	2	2
SMO	0.015	0.034	-9999	-0.75	1	1
ARRB2	0.014	0.039	-9999	-0.86	1	1
GLI3/SPOP	0.061	0.025	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.005	-9999	-10000	0	0
SIN3/HDAC complex	-0.019	0.097	-9999	-0.52	18	18
GNAI1	0.011	0.059	-9999	-0.75	3	3
XPO1	0.019	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.014	0.061	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	18	18
mol:GDP	0.015	0.034	-9999	-0.74	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.034	-9999	-0.75	1	1
GNAI3	0.016	0.005	-9999	-10000	0	0
GLI2	0.058	0.03	-9999	-10000	0	0
GLI3	0.055	0.026	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0.034	-9999	-0.75	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.044	0.053	-9999	-0.55	1	1
SIN3B	0.015	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.057	0.044	-9999	-10000	0	0
GLI2/Su(fu)	0.075	0.037	-9999	-10000	0	0
FOXA2	-0.063	0.23	-9999	-0.83	38	38
neural tube patterning	0.054	0.094	-9999	-0.5	2	2
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.014	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.014	0.034	-9999	-0.75	1	1
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.023	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	0.054	0.094	-9999	-0.5	2	2
SUFU	0.037	0.022	-9999	-10000	0	0
LGALS3	-0.005	0.13	-9999	-0.86	12	12
catabolic process	0.093	0.03	-9999	-10000	0	0
GLI3A/CBP	0.017	0.055	-9999	-10000	0	0
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.055	0.095	-9999	-0.51	2	2
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.013	0.083	-9999	-0.54	12	12
GNAZ	0.011	0.059	-9999	-0.75	3	3
RBBP4	0.014	0.034	-9999	-0.75	1	1
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.062	0.028	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.051	0.048	-9999	-0.49	1	1
PTCH1	0.061	0.1	-9999	-1.1	1	1
MIM/GLI1	0.05	0.15	-9999	-0.71	1	1
CREBBP	0.017	0.055	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.057	0.048	-9999	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	0.027	0.1	-9999	-0.41	1	1
BAG4	0.014	0.034	-9999	-0.75	1	1
BAD	0.03	0.046	-9999	-0.42	2	2
NFKBIA	0.016	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	78	78
BAX	0.031	0.036	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.027	-9999	-0.099	1	1
IKBKB	0.037	0.096	-9999	-10000	0	0
MAP2K2	0.046	0.053	-9999	-0.38	4	4
MAP2K1	0.047	0.051	-9999	-0.38	4	4
SMPD1	0.019	0.027	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.037	0.098	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.039	0.097	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.052	-9999	-0.38	4	4
response to UV	0.001	0	-9999	-0.003	4	4
RAF1	0.039	0.053	-9999	-0.41	4	4
CRADD	0.016	0.001	-9999	-10000	0	0
mol:ceramide	0.022	0.038	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.016	0.001	-9999	-10000	0	0
MAP3K1	0.032	0.036	-9999	-10000	0	0
TRADD	0.016	0.001	-9999	-10000	0	0
RELA/p50	0.016	0	-9999	-10000	0	0
MAPK3	0.05	0.051	-9999	-0.37	4	4
MAPK1	0.05	0.051	-9999	-0.37	4	4
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.027	0.1	-9999	-10000	0	0
KSR1	0.029	0.056	-9999	-0.45	4	4
MAPK8	0.049	0.033	-9999	-10000	0	0
TRAF2	0.016	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.037	0.096	-9999	-10000	0	0
TNF R/SODD	-0.001	0.025	-9999	-0.56	1	1
TNF	0.003	0.1	-9999	-0.8	8	8
CYCS	0.032	0.038	-9999	-10000	0	0
IKBKG	0.037	0.096	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.017	0.1	-9999	-0.44	1	1
RELA	0.016	0	-9999	-10000	0	0
RIPK1	0.016	0.001	-9999	-10000	0	0
AIFM1	0.033	0.038	-9999	-10000	0	0
TNF/TNF R/SODD	-0.009	0.069	-9999	-0.52	9	9
TNFRSF1A	0.016	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.03	-9999	-10000	0	0
NSMAF	0.028	0.099	-9999	-10000	0	0
response to hydrogen peroxide	0.001	0	-9999	-0.003	4	4
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.073	-9999	-0.73	5	5
VDR	0.011	0.059	-9999	-0.75	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.076	0.051	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.086	0.063	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.009	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.073	-9999	-10000	0	0
RXRs/NUR77	-0.008	0.089	-9999	-0.5	6	6
RXRs/PPAR	0.058	0.03	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.044	-9999	-0.57	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.04	-9999	-10000	0	0
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.058	-9999	-0.75	3	3
RARs/RARs/DNA/9cRA	-0.001	0.026	-9999	-0.41	2	2
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.035	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.073	-9999	-10000	0	0
THRA	0.014	0.034	-9999	-0.75	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.044	-9999	-0.57	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	0.005	0.057	-9999	-0.5	4	4
NR1H4	-0.01	0.14	-9999	-0.75	17	17
RXRs/LXRs/DNA	0.008	0.057	-9999	-10000	0	0
NR1H2	0.023	0.034	-9999	-0.74	1	1
NR1H3	0.025	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.053	-9999	-0.48	4	4
NR4A1	-0.007	0.13	-9999	-0.76	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.04	0.069	-9999	-0.41	2	2
RXRG	0.015	0.078	-9999	-0.85	4	4
RXR alpha/CCPG	0	0.004	-9999	-10000	0	0
RXRA	0.024	0.005	-9999	-10000	0	0
RXRB	0.025	0.006	-9999	-10000	0	0
THRB	-0.031	0.18	-9999	-0.75	31	31
PPARG	0.016	0	-9999	-10000	0	0
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.084	0.13	-9999	-0.87	8	8
mol:Oxysterols	0.009	0.007	-9999	-10000	0	0
cholesterol transport	0.086	0.063	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.013	0.048	-9999	-0.75	2	2
RXRs/NUR77/BCL2	-0.01	0.056	-9999	-10000	0	0
SREBF1	0.092	0.066	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.057	-9999	-0.5	4	4
ABCA1	0.091	0.072	-9999	-0.65	2	2
RARs/THRs	-0.027	0.099	-9999	-10000	0	0
RXRs/FXR	-0.009	0.094	-9999	-0.5	7	7
BCL2	0.016	0	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.075	0.027	-10000	0	-10000	0	0
NFATC2	0.054	0.029	-10000	0	-10000	0	0
NFATC3	0.028	0.04	-10000	0	-0.49	3	3
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.032	0.072	-10000	0	-0.46	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	-0.013	0.054	-10000	0	-0.52	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+	0	0.001	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0.003	-10000	0	-10000	0	0
BAD	0.012	0.052	-10000	0	-0.8	2	2
CABIN1/MEF2D	0.037	0.068	-10000	0	-0.43	4	4
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.034	-10000	0	-0.75	1	1
activation-induced cell death of T cells	-0.037	0.067	0.43	4	-10000	0	4
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
SFN	-0.086	0.28	-10000	0	-0.83	61	61
MAP3K8	0.013	0.055	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.002	0.024	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.01	0.056	-10000	0	-10000	0	0
CABIN1	0.032	0.073	-10000	0	-0.47	4	4
CALM1	0.016	0.003	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0.013	0.048	-10000	0	-0.75	2	2
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.035	-10000	0	-0.56	2	2
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0.003	-10000	0	-10000	0	0
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.028	-10000	0	-10000	0	0
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.025	-10000	0	-0.56	1	1
CASP3	0.016	0.003	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.001	0.02	-10000	0	-0.39	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.029	0.077	-10000	0	-0.47	2	2
PRKCB	0.007	0.082	-10000	0	-0.82	5	5
PRKCE	0.014	0.034	-10000	0	-0.75	1	1
JNK2/NFAT4	-0.003	0.034	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.002	0.039	-10000	0	-0.61	2	2
PRKCD	0.014	0.039	-10000	0	-0.86	1	1
NUP214	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.059	-10000	0	-0.75	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.03	0.18	-10000	0	-0.86	22	22
PRKCQ	-0.007	0.13	-10000	0	-0.75	15	15
FKBP38/BCL2	-0.001	0.025	-10000	0	-0.56	1	1
EP300	0.015	0.034	-10000	0	-0.74	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.08	0.029	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.001	0.022	-10000	0	-0.5	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.031	-10000	0	-0.49	2	2
NFATc/ERK1	0.081	0.026	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.013	0.055	-10000	0	-0.53	2	2
NR4A1	0.073	0.13	-10000	0	-0.67	15	15
GSK3B	0.016	0.003	-10000	0	-10000	0	0
positive T cell selection	0.028	0.04	-10000	0	-0.49	3	3
NFAT1/CK1 alpha	-0.002	0.015	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0.003	-10000	0	-10000	0	0
AKAP5	0.013	0.048	-10000	0	-0.75	2	2
MEF2D	0.016	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.08	0.029	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.008	0.059	-9999	-0.55	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.049	-9999	-0.54	1	1
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.059	-9999	-0.75	3	3
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	-0.003	0.022	-9999	-10000	0	0
YY1/LSF	-0.001	0.032	-9999	-0.73	1	1
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.041	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.003	0.027	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.046	0.043	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	-0.003	0.027	-9999	-10000	0	0
NuRD/MBD3 Complex	0.063	0.025	-9999	-0.46	1	1
NF kappa B1 p50/RelA	0.048	0.048	-9999	-0.65	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.002	0.12	-9999	-0.75	12	12
GATA1	-0.021	0.17	-9999	-0.86	20	20
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.009	0.046	-9999	-0.53	2	2
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.014	0.034	-9999	-0.75	1	1
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	-0.004	0.032	-9999	-10000	0	0
KAT2B	0.014	0.034	-9999	-0.75	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.008	0.038	-9999	-10000	0	0
SIN3 complex	-0.019	0.096	-9999	-0.52	18	18
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	18	18
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	-0.004	0.037	-9999	-0.64	1	1
YY1/HDAC2	-0.001	0.032	-9999	-0.73	1	1
YY1/HDAC1	-0.001	0.032	-9999	-0.73	1	1
NuRD/MBD2 Complex (MeCP1)	0.064	0.011	-9999	-10000	0	0
PPARG	-0.006	0.048	-9999	-0.4	4	4
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.003	0.027	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.001	0.025	-9999	-0.52	1	1
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	-0.004	0.032	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.039	0.038	-9999	-0.81	1	1
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.034	0.019	-9999	-0.4	1	1
NFKB1	0.014	0.034	-9999	-0.75	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.03	-9999	-0.67	1	1
YY1/SAP30/HDAC1	-0.019	0.098	-9999	-0.52	19	19
EP300	0.014	0.034	-9999	-0.75	1	1
STAT3 (dimer non-phopshorylated)	0.034	0.019	-9999	-0.4	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.032	-9999	-10000	0	0
histone deacetylation	0.063	0.011	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.004	0.027	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	-0.014	0.07	-9999	-0.42	12	12
GATA1/HDAC1	-0.026	0.13	-9999	-0.66	20	20
GATA1/HDAC3	-0.024	0.1	-9999	-0.52	20	20
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.01	0.077	-9999	-0.61	8	8
SIN3/HDAC complex/Mad/Max	0.056	0.041	-9999	-10000	0	0
NuRD Complex	-0.001	0.02	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.022	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.019	-9999	-10000	0	0
GATA1/Fog1	-0.03	0.14	-9999	-0.65	23	23
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
negative regulation of cell growth	0.056	0.04	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.064	0.011	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.046	-9999	-0.38	4	4
SIN3/HDAC complex/NCoR1	-0.006	0.029	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.012	0.052	-9999	-0.8	2	2
MBD2	0.016	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.011	0.059	-9999	-0.75	3	3
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.006	0.038	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	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	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
MAP3K12	0.014	0.034	-9999	-0.75	1	1
FGR	0.011	0.067	-9999	-0.86	3	3
p38 alpha/TAB1	-0.012	0.038	-9999	-0.31	2	2
PRKG1	-0.002	0.12	-9999	-0.75	12	12
DUSP8	0.014	0.034	-9999	-0.75	1	1
PGK/cGMP/p38 alpha	-0.018	0.062	-9999	-0.34	12	12
apoptosis	-0.012	0.037	-9999	-0.3	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
DUSP1	0.014	0.039	-9999	-0.86	1	1
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	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	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.056	0.085	-9999	-0.42	2	2
BLK	-0.04	0.21	-9999	-0.86	32	32
HCK	-0.033	0.2	-9999	-0.86	28	28
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.011	0.067	-9999	-0.86	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.056	0.066	-9999	-0.34	2	2
positive regulation of innate immune response	0.067	0.092	-9999	-0.44	2	2
LCK	-0.022	0.18	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.073	0.088	-9999	-10000	0	0
p38alpha-beta/MKP5	0.07	0.094	-9999	-10000	0	0
PGK/cGMP	-0.014	0.087	-9999	-0.57	12	12
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.072	0.09	-9999	-0.42	2	2
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.008	0.14	-9999	-0.83	14	14

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.004	0.13	-9999	-0.81	12	12
CLTC	0.043	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.036	0	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
CD59	0.039	0	-9999	-10000	0	0
CPE	-0.001	0.12	-9999	-0.58	22	22
CTNNB1	0.016	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	0.044	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.044	0	-9999	-10000	0	0
TSHR	-0.045	0.2	-9999	-0.59	58	58
INS	0.017	0.001	-9999	-10000	0	0
BIN1	0.016	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.025	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.038	0.022	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.028	0.056	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	-0.048	0.23	-9999	-0.86	37	37
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.016	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.058	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.006	0.031	-9999	-10000	0	0
positive regulation of phagocytosis	0.025	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.043	0.15	-9999	-0.58	37	37
ACAP1	-0.019	0.024	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.032	0.012	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.043	0.011	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.016	0	-9999	-10000	0	0
exocyst	0	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0.044	0	-9999	-10000	0	0
NME1	0.025	0	-9999	-10000	0	0
clathrin coat assembly	0.043	0	-9999	-10000	0	0
IL2RA	-0.016	0.11	-9999	-10000	0	0
VAMP3	0.025	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.061	-9999	-0.43	7	7
EXOC6	0.016	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.016	0	-9999	-10000	0	0
PIP5K1C	0.045	0	-9999	-10000	0	0
SDC1	0.036	0.03	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
EXOC7	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.007	0.031	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.016	0	-9999	-10000	0	0
ADRB2	0.05	0.027	-9999	-0.37	2	2
EXOC3	0.016	0	-9999	-10000	0	0
ASAP2	0.016	0	-9999	-10000	0	0
Dynamin 2/GDP	0	0	-9999	-10000	0	0
KLC1	0.016	0	-9999	-10000	0	0
AVPR2	-0.13	0.21	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.026	-9999	-10000	0	0

×

IGF1 pathway

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
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	0.029	0.055	-10000	0	-0.41	6	6
GRB2/SOS1/SHC	-0.001	0.025	-10000	0	-0.57	1	1
HRAS	0.014	0.039	-10000	0	-0.86	1	1
IRS1/Crk	-0.007	0.05	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.056	-10000	0	-0.52	6	6
AKT1	0.055	0.061	-10000	0	-0.72	1	1
BAD	0.062	0.072	-10000	0	-1.1	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.055	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.05	-10000	0	-0.41	6	6
RAF1	0.068	0.057	-10000	0	-0.7	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.047	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.055	-10000	0	-0.45	6	6
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
RPS6KB1	0.055	0.061	-10000	0	-0.72	1	1
GNB2L1	0.014	0.039	-10000	0	-0.86	1	1
positive regulation of MAPKKK cascade	0.059	0.05	-10000	0	-0.57	1	1
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.007	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.049	-10000	0	-0.5	1	1
IGF-1R heterotetramer	0.015	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.05	-10000	0	-0.41	6	6
Crk/p130 Cas/Paxillin	-0.007	0.046	-10000	0	-10000	0	0
IGF1R	0.015	0.012	-10000	0	-10000	0	0
IGF1	0.006	0.094	-10000	0	-0.85	6	6
IRS2/Crk	0.029	0.083	-10000	0	-0.48	8	8
PI3K	-0.008	0.052	-10000	0	-10000	0	0
apoptosis	-0.066	0.06	0.79	1	-10000	0	1
HRAS/GDP	-0.001	0.03	-10000	0	-0.68	1	1
PRKCD	0.05	0.057	-10000	0	-0.82	1	1
RAF1/14-3-3 E	0.071	0.05	-10000	0	-0.57	1	1
BAD/14-3-3	0.068	0.065	-10000	0	-0.89	1	1
PRKCZ	0.052	0.069	-10000	0	-0.72	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.006	0.043	-10000	0	-0.57	1	1
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.042	0.048	-10000	0	-10000	0	0
BCAR1	0.014	0.034	-10000	0	-0.75	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.007	0.054	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.007	0.05	-10000	0	-0.41	6	6
GRB10	0.016	0	-10000	0	-10000	0	0
PTPN11	0.029	0.055	-10000	0	-0.41	6	6
IRS1	0.019	0.059	-10000	0	-0.42	9	9
IRS2	0.02	0.087	-10000	0	-0.47	14	14
IGF-1R heterotetramer/IGF1	-0.008	0.071	-10000	0	-0.65	6	6
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	0.045	0.064	-10000	0	-0.77	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0
PRKD1	0.05	0.049	-10000	0	-10000	0	0
SHC1	0.014	0.039	-10000	0	-0.86	1	1

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.008	0.058	-9999	-10000	0	0
TC10/GTP	-0.006	0.049	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.034	-9999	-10000	0	0
HRAS	0.014	0.039	-9999	-0.86	1	1
APS homodimer	0.007	0.087	-9999	-0.86	5	5
GRB14	-0.027	0.17	-9999	-0.75	28	28
FOXO3	-0.003	0.013	-9999	-10000	0	0
AKT1	-0.022	0.086	-9999	-0.66	2	2
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
SORBS1	0.014	0.034	-9999	-0.75	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.005	0.14	-9999	-0.51	36	36
CBL/APS/CAP/Crk-II/C3G	-0.006	0.054	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.034	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.038	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.022	-9999	-10000	0	0
RPS6KB1	0.055	0.096	-9999	-0.59	2	2
PARD6A	0.011	0.059	-9999	-0.75	3	3
CBL	0.014	0.034	-9999	-0.75	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.019	0.075	-9999	-0.59	2	2
HRAS/GTP	-0.007	0.054	-9999	-0.73	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.003	0.038	-9999	-10000	0	0
PRKCI	-0.005	0.02	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.024	0.094	-9999	-0.73	2	2
SHC1	0.014	0.039	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	-0.002	0.037	-9999	-0.82	1	1
PI3K	-0.004	0.039	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.03	-9999	-0.68	1	1
AKT2	-0.022	0.086	-9999	-0.66	2	2
PRKCZ	-0.009	0.057	-9999	-0.7	3	3
SH2B2	0.007	0.087	-9999	-0.86	5	5
SHC/SHIP	-0.007	0.062	-9999	-0.57	4	4
F2RL2	-0.035	0.2	-9999	-0.86	29	29
TRIP10	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.024	-9999	-0.55	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.022	-9999	-0.5	1	1
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.034	-9999	-0.75	1	1
NCK1	0.014	0.034	-9999	-0.75	1	1
CBL/APS/CAP/Crk-II	-0.007	0.058	-9999	-0.52	5	5
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.024	-9999	-0.54	1	1
INPP5D	0.03	0.066	-9999	-0.61	4	4
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.001	0.006	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.011	0.059	-9999	-0.75	3	3
p62DOK/RasGAP	-0.002	0.037	-9999	-0.84	1	1
INS	0.005	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	0.03	0.065	-9999	-0.6	4	4
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.033	0.14	-9999	-0.74	5	5
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.014	0.034	-9999	-0.75	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.002	0.026	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.035	-9999	-0.46	3	3
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.031	0.12	-9999	-0.5	29	29

×

PDGFR-beta signaling 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
S1P1/Sphingosine-1-phosphate	-0.035	0.12	-9999	-0.48	9	9
PDGFB-D/PDGFRB/SLAP	-0.032	0.14	-9999	-0.67	24	24
PDGFB-D/PDGFRB/APS/CBL	-0.007	0.061	-9999	-0.56	6	6
AKT1	-0.002	0.022	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.014	0.14	-9999	-0.49	9	9
PIK3CA	0.014	0.034	-9999	-0.75	1	1
FGR	-0.003	0.029	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.043	0.13	-9999	-0.57	18	18
SHC1	0.014	0.039	-9999	-0.86	1	1
HRAS/GDP	-0.002	0.039	-9999	-0.88	1	1
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.038	0.041	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.005	0.089	-9999	-0.75	7	7
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	-0.032	0.14	-9999	-0.67	24	24
HRAS	0.014	0.039	-9999	-0.86	1	1
HIF1A	0.087	0.041	-9999	-0.6	1	1
GAB1	0.033	0.075	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.036	0.081	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.012	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.037	0.12	-9999	-0.53	6	6
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
mol:IP3	0.038	0.041	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.066	-9999	-0.57	7	7
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.086	-9999	-10000	0	0
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.034	-9999	-0.75	1	1
VAV2	0.036	0.087	-9999	-10000	0	0
CBL	0.014	0.034	-9999	-0.75	1	1
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	-0.018	0.082	-9999	-0.64	2	2
PDGFRB	0.016	0.006	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.02	0.082	-9999	-10000	0	0
ABL1	0.034	0.06	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.033	0.07	-9999	-10000	0	0
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.014	0.039	-9999	-0.86	1	1
cell proliferation	0.044	0.12	-9999	-0.51	18	18
SLA	-0.026	0.19	-9999	-0.86	24	24
actin cytoskeleton reorganization	0.001	0.025	-9999	-10000	0	0
SRC	-0.001	0.013	-9999	-10000	0	0
PI3K	-0.002	0.025	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.008	0.062	-9999	-0.49	8	8
SH2B2	0.007	0.087	-9999	-0.86	5	5
PLCgamma1/SPHK1	0.013	0.14	-9999	-0.51	9	9
LYN	-0.001	0.013	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.024	-9999	-10000	0	0
SPHK1	-0.055	0.24	-9999	-0.86	41	41
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.038	0.041	-9999	-10000	0	0
PLCG1	0.039	0.041	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.021	-9999	-0.48	1	1
YES1	-0.001	0.013	-9999	-10000	0	0
cell migration	-0.001	0.021	-9999	-0.48	1	1
SHC/Grb2/SOS1	-0.001	0.021	-9999	-10000	0	0
SLC9A3R2	0.014	0.034	-9999	-0.75	1	1
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.019	-9999	-10000	0	0
FYN	-0.001	0.013	-9999	-10000	0	0
DOK1	0.044	0.009	-9999	-10000	0	0
HRAS/GTP	-0.001	0.03	-9999	-0.68	1	1
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	0.046	0.1	-9999	-10000	0	0
PRKCD	0.042	0.029	-9999	-0.53	1	1
FER	0.041	0.033	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.022	-9999	-10000	0	0
RASA1	0.042	0.025	-9999	-10000	0	0
NCK1	0.014	0.034	-9999	-0.75	1	1
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.033	0.059	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.02	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0.016	0	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.019	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	-0.026	0.13	-10000	0	-0.66	20	20
GATA1/HDAC5	-0.027	0.13	-10000	0	-0.66	21	21
GATA2/HDAC5	-0.014	0.089	-10000	0	-0.56	13	13
HDAC5/BCL6/BCoR	-0.001	0.021	-10000	0	-0.48	1	1
HDAC9	0.016	0	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.025	-10000	0	-0.57	1	1
HDAC4/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC5/YWHAB	-0.001	0.025	-10000	0	-0.56	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.002	0.12	-10000	0	-0.75	12	12
HDAC4/RFXANK	-0.001	0.029	-10000	0	-0.66	1	1
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.014	0.034	-10000	0	-0.75	1	1
HDAC5	0.014	0.034	-10000	0	-0.75	1	1
GNB1/GNG2	0	0	-10000	0	-10000	0	0
Histones	-0.003	0.041	-10000	0	-0.84	1	1
ADRBK1	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	-0.001	0.025	-10000	0	-0.56	1	1
HDAC4/Ubc9	0	0	-10000	0	-10000	0	0
HDAC7	0.016	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.025	-10000	0	-0.56	1	1
TUBA1B	0.016	0	-10000	0	-10000	0	0
HDAC6	0.016	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.002	0.039	-10000	0	-0.61	2	2
CAMK4	0.013	0.048	-10000	0	-0.75	2	2
Tubulin/HDAC6	-0.001	0.021	-10000	0	-0.48	1	1
SUMO1	0.016	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
GATA1	-0.021	0.17	-10000	0	-0.86	20	20
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.016	0	-10000	0	-10000	0	0
NR3C1	0.014	0.039	-10000	0	-0.86	1	1
SUMO1/HDAC4	0	0	-10000	0	-10000	0	0
SRF	0.016	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0	0	-10000	0	-10000	0	0
Tubulin	-0.001	0.025	-10000	0	-0.56	1	1
HDAC4/14-3-3 E	0	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
RANGAP1	0.016	0	-10000	0	-10000	0	0
BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-10000	0	-10000	0	0
HDAC4/SRF	-0.002	0.03	-10000	0	-0.48	2	2
HDAC4/ER alpha	-0.005	0.052	-10000	0	-0.59	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.051	0.044	-10000	0	-0.83	1	1
cell motility	-0.001	0.021	-10000	0	-0.48	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	0.016	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
ESR1	0.009	0.07	-10000	0	-0.78	4	4
HDAC6/HDAC11	-0.002	0.035	-10000	0	-0.56	2	2
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0.016	0	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
NCOR2	0.016	0	-10000	0	-10000	0	0
TUBB2A	0.014	0.034	-10000	0	-0.75	1	1
HDAC11	0.013	0.048	-10000	0	-0.75	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RANBP2	0.016	0	-10000	0	-10000	0	0
ANKRA2	0.016	0	-10000	0	-10000	0	0
RFXANK	0.014	0.039	-10000	0	-0.86	1	1
nuclear import	0.001	0.018	0.39	1	-10000	0	1

×

Circadian rhythm 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
chromatin modification	-0.001	0.013	-10000	0	-10000	0	0
CLOCK	0.019	0.034	-10000	0	-0.74	1	1
TIMELESS/CRY2	0.056	0.022	-10000	0	-10000	0	0
DEC1/BMAL1	-0.001	0.029	-10000	0	-0.66	1	1
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.054	0.063	-10000	0	-1.3	1	1
ARNTL	0.02	0.002	-10000	0	-10000	0	0
TIMELESS	0.056	0.025	-10000	0	-10000	0	0
NPAS2	0.005	0.11	-10000	0	-0.74	10	10
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.007	0.14	1	-10000	0	1
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.007	-10000	0	-0.14	1	1
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.044	0.076	-10000	0	-0.46	11	11
BMAL1/CLOCK	0.065	0.051	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.013	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.013	-10000	0	-10000	0	0
mol:NADPH	0.019	0.007	-10000	0	-0.14	1	1
PER1/TIMELESS	0.056	0.022	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.001	0.039	-10000	0	-0.86	1	1

×

mTOR signaling 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	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	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.003	0.035	-10000	0	-0.4	2	2
FRAP1	0.02	0.012	-10000	0	-10000	0	0
AKT1	-0.003	0.036	-10000	0	-0.58	1	1
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.028	-10000	0	-0.46	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.009	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.002	0.025	-10000	0	-0.42	1	1
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.018	0.031	-10000	0	-0.39	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.036	0.024	-10000	0	-0.34	1	1
MAP3K5	0.014	0.001	-10000	0	-10000	0	0
PIK3R1	0.014	0.034	-10000	0	-0.75	1	1
apoptosis	0.014	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	3	3
EIF4B	0.044	0.021	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.032	-10000	0	-0.45	2	2
eIF4E/eIF4G1/eIF4A1	0	0.005	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.004	0.037	-10000	0	-0.37	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.042	0.018	-10000	0	-0.24	1	1
FKBP1A	0.016	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.024	-10000	0	-0.41	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	3	3
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.004	0.043	-10000	0	-0.75	1	1
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.008	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.023	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.003	0.03	-10000	0	-0.5	1	1
tumor necrosis factor receptor activity	0	0	0.002	3	-10000	0	3
RPS6	0.012	0.055	-10000	0	-0.86	2	2
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.009	0.033	-10000	0	-0.42	3	3
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.003	0.032	-10000	0	-0.39	1	1
EIF4EBP1	-0.007	0.1	-10000	0	-0.46	24	24
PIK3CA	0.014	0.034	-10000	0	-0.75	1	1
PPP2R5D	0.029	0.012	-10000	0	-10000	0	0
peptide biosynthetic process	0.023	0.001	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-0.004	1	1
EEF2	0.023	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.003	0.089	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.031	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.002	0.03	-9999	-0.52	1	1
CDKN1B	0.051	0.007	-9999	-10000	0	0
CDKN1A	0.048	0.033	-9999	-0.47	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.051	0.007	-9999	-10000	0	0
AKT1	0	0.006	-9999	-10000	0	0
BAD	0.012	0.052	-9999	-0.8	2	2
AKT3	0.022	0.019	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.051	0.007	-9999	-10000	0	0
AKT1/ASK1	0	0.005	-9999	-10000	0	0
BAD/YWHAZ	-0.002	0.033	-9999	-0.52	2	2
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.016	0	-9999	-10000	0	0
JNK cascade	0	0.005	-9999	-10000	0	0
TSC1	0.051	0.007	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0	0.005	-9999	-10000	0	0
EP300	0.014	0.034	-9999	-0.75	1	1
mol:GDP	0	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.051	0.007	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.033	0.017	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.04	0.053	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.051	0.007	-9999	-10000	0	0
CASP9	0.051	0.007	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.057	0.007	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.021	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.031	-9999	-0.44	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.003	-9999	-10000	0	0
CHUK	0.051	0.007	-9999	-10000	0	0
BAD/BCL-XL	-0.002	0.029	-9999	-0.56	1	1
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.022	0.019	-9999	-0.41	1	1
FOXO1-3a-4/14-3-3 family	0.059	0.06	-9999	-10000	0	0
PDPK1	0.014	0.034	-9999	-0.75	1	1
MDM2	0.051	0.007	-9999	-10000	0	0
MAPKKK cascade	0	0.005	-9999	-10000	0	0
MDM2/Cbp/p300	-0.001	0.021	-9999	-10000	0	0
TSC1/TSC2	0.059	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.02	-9999	-10000	0	0
glucose import	0.029	0.081	-9999	-0.52	7	7
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0.005	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.029	0.082	-9999	-0.52	7	7
GSK3A	0.051	0.007	-9999	-10000	0	0
FOXO1	0.051	0.007	-9999	-10000	0	0
GSK3B	0.051	0.007	-9999	-10000	0	0
SFN	-0.086	0.28	-9999	-0.83	61	61
G1/S transition of mitotic cell cycle	0.06	0.007	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.035	0.079	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.003	0.043	-9999	-0.56	3	3
PTK2	-0.003	0.03	-9999	-10000	0	0
positive regulation of JNK cascade	-0.002	0.023	-9999	-10000	0	0
CDC42/GDP	0.077	0.032	-9999	-10000	0	0
Rac1/GDP	0.08	0.032	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.002	0.028	-9999	-10000	0	0
nectin-3/I-afadin	-0.002	0.035	-9999	-0.56	2	2
RAPGEF1	0.075	0.034	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.068	0.037	-9999	-0.51	2	2
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	0.046	0.016	-9999	-10000	0	0
Rap1/GTP	-0.001	0.019	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.002	0.035	-9999	-0.56	2	2
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.079	0.038	-9999	-0.48	2	2
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.034	-9999	-0.75	1	1
PI3K	-0.003	0.035	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.001	0.019	-9999	-10000	0	0
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	0.013	0.048	-9999	-0.75	2	2
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.034	-9999	-0.75	1	1
CDH1	-0.016	0.15	-9999	-0.75	21	21
CLDN1	0.008	0.08	-9999	-0.79	5	5
JAM-A/CLDN1	-0.006	0.053	-9999	-0.52	2	2
SRC	-0.003	0.036	-9999	-0.57	2	2
ITGB3	0.011	0.059	-9999	-0.75	3	3
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.069	0.045	-9999	-0.5	3	3
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.002	0.03	-9999	-0.48	2	2
nectin-1/I-afadin	0	0	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.002	0.03	-9999	-0.48	2	2
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.016	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.002	0.023	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.003	0.029	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.001	0.014	-9999	-10000	0	0
VAV2	0.069	0.036	-9999	-0.48	2	2
RAP1/GDP	-0.002	0.023	-9999	-10000	0	0
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.03	-9999	-0.48	2	2
nectin-3(dimer)/I-afadin/I-afadin	-0.002	0.035	-9999	-0.56	2	2
Rac1/GTP	-0.002	0.024	-9999	-0.37	2	2
PTPRM	-0.001	0.017	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.074	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.011	0.059	-10000	0	-0.75	3	3
Cbp/p300/PCAF	-0.002	0.041	-10000	0	-0.92	1	1
EP300	0.014	0.034	-10000	0	-0.75	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.056	0.034	-10000	0	-0.44	1	1
KAT2B	0.014	0.034	-10000	0	-0.75	1	1
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.031	0.038	0.24	1	-0.3	2	3
RAR alpha/9cRA/Cyclin H	-0.008	0.036	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.053	0.037	-10000	0	-0.48	1	1
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.002	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.009	0.039	-10000	0	-10000	0	0
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.044	-10000	0	-0.57	3	3
RXRs/RARs/NRIP1/9cRA	0.063	0.081	-10000	0	-0.52	1	1
NCOA2	0.004	0.095	-10000	0	-0.75	8	8
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.058	-10000	0	-0.75	3	3
RARG	0.017	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.017	0.001	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.017	0.001	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.018	0.073	-10000	0	-10000	0	0
RARA	0.026	0.057	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.048	0.061	-10000	0	-0.89	1	1
PRKCA	0.021	0.001	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.055	0.083	-10000	0	-0.57	1	1
RXRG	0.012	0.091	-10000	0	-0.38	26	26
RXRA	0.037	0.054	-10000	0	-10000	0	0
RXRB	0.017	0.084	-10000	0	-0.37	22	22
VDR/Vit D3/DNA	-0.003	0.044	-10000	0	-0.57	3	3
RBP1	0.009	0.075	-10000	0	-0.83	4	4
CRBP1/9-cic-RA	-0.005	0.058	-10000	0	-0.65	4	4
RARB	0.016	0.048	-10000	0	-0.75	2	2
PRKCG	-0.025	0.18	-10000	0	-0.86	22	22
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.054	0.083	-10000	0	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.061	0.074	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.046	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.055	0.083	-10000	0	-0.57	1	1
positive regulation of DNA binding	-0.008	0.035	-10000	0	-10000	0	0
NRIP1	0.053	0.092	-10000	0	-1.2	1	1
RXRs/RARs	0.046	0.081	-10000	0	-0.41	1	1
RXRs/RXRs/DNA/9cRA	-0.017	0.073	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.025	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.003	0.042	-9999	-0.66	2	2
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.004	0.042	-9999	-0.48	4	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.039	-9999	-10000	0	0
NFKBIA	0.028	0.056	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.021	-9999	-0.48	1	1
ARRB2	0.022	0.018	-9999	-0.39	1	1
REL	0.011	0.059	-9999	-0.75	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.003	0.042	-9999	-0.54	3	3
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.021	-9999	-0.48	1	1
PIK3CA	0.014	0.034	-9999	-0.75	1	1
NF kappa B1 p50 dimer	0.025	0.026	-9999	-0.56	1	1
PIK3R1	0.014	0.034	-9999	-0.75	1	1
NFKB1	0.03	0.026	-9999	-0.56	1	1
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.036	0.055	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.008	0.037	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.035	-9999	-0.56	2	2
NF kappa B1 p50/RelA	0.036	0.056	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.013	0.048	-9999	-0.75	2	2
I kappa B alpha/PIK3R1	0.034	0.056	-9999	-0.39	1	1
cell death	-0.008	0.036	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.004	0.042	-9999	-0.48	4	4
LCK	-0.022	0.18	-9999	-0.85	22	22
BCL3	0.012	0.055	-9999	-0.86	2	2

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.011	0.25	-9999	-1.1	24	24
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.024	0.071	-9999	-10000	0	0
ATF2/c-Jun	0.045	0.062	-9999	-0.61	1	1
MAPK11	0.022	0.081	-9999	-0.84	1	1
MITF	0.045	0.088	-9999	-10000	0	0
MAPKAPK5	0.045	0.088	-9999	-10000	0	0
KRT8	0.044	0.09	-9999	-10000	0	0
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.033	0.11	-9999	-0.62	1	1
CEBPB	0.035	0.11	-9999	-10000	0	0
SLC9A1	0.045	0.088	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.051	0.093	-9999	-0.82	1	1
p38alpha-beta/MNK1	-0.018	0.072	-9999	-10000	0	0
JUN	0.046	0.062	-9999	-0.6	1	1
PPARGC1A	0.002	0.15	-9999	-0.75	2	2
USF1	0.045	0.088	-9999	-10000	0	0
RAB5/GDP/GDI1	-0.013	0.049	-9999	-10000	0	0
NOS2	0.039	0.13	-9999	-0.84	7	7
DDIT3	0.042	0.093	-9999	-10000	0	0
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.048	0.084	-9999	-0.67	2	2
p38alpha-beta/HBP1	-0.018	0.072	-9999	-10000	0	0
CREB1	0.05	0.091	-9999	-10000	0	0
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.049	0.076	-9999	-10000	0	0
RPS6KA4	0.045	0.088	-9999	-10000	0	0
PLA2G4A	0.044	0.094	-9999	-0.88	1	1
GDI1	0.045	0.088	-9999	-10000	0	0
TP53	0.047	0.11	-9999	-10000	0	0
RPS6KA5	0.045	0.088	-9999	-10000	0	0
ESR1	0.041	0.095	-9999	-10000	0	0
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.045	0.088	-9999	-10000	0	0
MEF2A	0.045	0.088	-9999	-10000	0	0
EIF4EBP1	0.044	0.094	-9999	-0.43	1	1
KRT19	-0.042	0.21	-9999	-0.88	9	9
ELK4	0.045	0.088	-9999	-10000	0	0
ATF6	0.045	0.088	-9999	-10000	0	0
ATF1	0.05	0.091	-9999	-10000	0	0
p38alpha-beta/MAPKAPK2	-0.018	0.072	-9999	-10000	0	0
p38alpha-beta/MAPKAPK3	-0.018	0.072	-9999	-0.5	1	1

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.005	0.059	-9999	-0.66	4	4
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.043	-9999	-0.48	4	4
NFKB1	0.014	0.034	-9999	-0.75	1	1
MAP3K14	0.009	0.078	-9999	-0.86	4	4
NF kappa B1 p50/RelB	-0.001	0.025	-9999	-0.56	1	1
RELB	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.019	0	-9999	-10000	0	0
SMAD3	0.057	0	-9999	-10000	0	0
SMAD3/SMAD4	0.062	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.027	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.001	0.025	-9999	-0.56	1	1
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.014	0.034	-9999	-0.75	1	1
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	0.016	0	-9999	-10000	0	0
PIAS4	0.016	0	-9999	-10000	0	0

×

TRAIL 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.014	0.034	-9999	-0.75	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.025	-9999	-0.56	1	1
MAP2K4	0.063	0.018	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.014	0.039	-9999	-0.86	1	1
TNFRSF10A	0.014	0.034	-9999	-0.75	1	1
SMPD1	-0.001	0.017	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.002	0.039	-9999	-0.61	2	2
TRAIL/TRAILR3	-0.002	0.039	-9999	-0.61	2	2
TRAIL/TRAILR1	-0.002	0.035	-9999	-0.56	2	2
TRAIL/TRAILR4	-0.001	0.025	-9999	-0.56	1	1
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.028	-9999	-0.44	2	2
IKK complex	-0.001	0.009	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.03	0.026	-9999	-0.56	1	1
MAP3K1	-0.001	0.015	-9999	-10000	0	0
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.034	-9999	-0.75	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.018	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
MAPK1	0.03	0.026	-9999	-0.56	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.025	-9999	-10000	0	0
mol:ceramide	-0.001	0.017	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.071	0.017	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.014	0.039	-9999	-0.86	1	1
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.03	-9999	-0.48	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.002	0.025	-9999	-10000	0	0
JNK cascade	-0.001	0.025	-9999	-0.56	1	1
TRAIL (trimer)	0.014	0.034	-9999	-0.75	1	1
TNFRSF10C	0.014	0.039	-9999	-0.86	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.025	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.002	0.033	-9999	-0.52	2	2
cell death	-0.001	0.017	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.018	-9999	-10000	0	0
TRAILR2 (trimer)	0.014	0.039	-9999	-0.86	1	1
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.028	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.016	-9999	-9999
NPC/RanGAP1/SUMO1	0	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.039	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.016	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.016	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.016	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.016	-9999	-9999
PIAS1	0.016	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0	-9999	-10000	0	0
MAPK9	0.011	0	-9999	-10000	0	0
adrenocorticotropin secretion	-0.003	0.068	-9999	-0.68	5	5
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0	-9999	-10000	0	0
Gs family/GTP	0	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	-0.005	0.086	-9999	-0.86	5	5
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.011	0.001	-9999	-10000	0	0
MAPK11	0.011	0.018	-9999	-0.4	1	1

×

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	-0.001	0.023	-9999	-0.52	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.027	0.009	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.002	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.001	-9999	-10000	0	0
CD4	0.002	0.11	-9999	-0.86	8	8
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.014	0.026	-9999	-0.57	1	1
mol:PI-4-5-P2	-0.001	0.017	-9999	-0.38	1	1
ARF1/GTP	0	0.009	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.021	-9999	-0.47	1	1
mol:Choline	-0.001	0.017	-9999	-0.38	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	-0.001	0.017	-9999	-0.39	1	1
ARF1/GDP	-0.001	0.021	-9999	-0.47	1	1
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.019	-9999	-0.42	1	1
ARFIP2	0	0.003	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.035	0.005	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.006	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.011	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.006	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.003	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-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	0.044	0.033	-9999	-10000	0	0
PLD2	-0.001	0.017	-9999	-0.38	1	1
ARF-GAP1/v-SNARE	0.014	0.026	-9999	-0.57	1	1
PIP5K1A	-0.001	0.017	-9999	-0.39	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.009	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.017	-9999	-0.38	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.014	0.026	-9999	-0.57	1	1
GOSR2	0	0.007	-9999	-10000	0	0
USO1	0	0.007	-9999	-10000	0	0
GBF1	0	0.007	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.002	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.009	0.072	-9999	-0.57	8	8

pid_entity	TCGA.MW.A4EC	TCGA.MM.A564	TCGA.EU.5907	TCGA.EU.5906
109_MAP3K5	0.074	0.074	0.074	0.074
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0	-0.75	-0.75	-0.75
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	-0.43	-0.43	-0.43	0
30_TGFB1/TGF beta receptor Type II	0.015	0.021	0.015	0.015
84_STAT5B	-0.031	-0.14	-0.031	-0.031
84_STAT5A	-0.031	-0.14	-0.031	-0.031