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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	374
HIF-1-alpha transcription factor network	200
Nephrin/Neph1 signaling in the kidney podocyte	172
TCR signaling in naïve CD8+ T cells	146
TCGA08_p53	142
Aurora B signaling	120
Syndecan-4-mediated signaling events	118
FOXA2 and FOXA3 transcription factor networks	117
IL12-mediated signaling events	107
FOXM1 transcription factor network	106

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	0.7220	374	2996	8	-0.84	0.22	1000	-1000	-0.035	-1000
HIF-1-alpha transcription factor network	0.3861	200	15233	76	-1.3	0.026	1000	-1000	-0.18	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3320	172	5853	34	-0.61	0.016	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.2819	146	13655	93	-0.66	0.33	1000	-1000	-0.12	-1000
TCGA08_p53	0.2741	142	999	7	-0.65	0.31	1000	-1000	-0.018	-1000
Aurora B signaling	0.2317	120	8050	67	-0.41	0.016	1000	-1000	-0.1	-1000
Syndecan-4-mediated signaling events	0.2278	118	7939	67	-0.65	0.11	1000	-1000	-0.14	-1000
FOXA2 and FOXA3 transcription factor networks	0.2259	117	5387	46	-1.2	0.025	1000	-1000	-0.083	-1000
IL12-mediated signaling events	0.2066	107	9314	87	-0.7	0.16	1000	-1000	-0.16	-1000
FOXM1 transcription factor network	0.2046	106	5441	51	-0.82	0.04	1000	-1000	-0.19	-1000
Glypican 1 network	0.1988	103	4964	48	-0.56	0.045	1000	-1000	-0.08	-1000
PDGFR-alpha signaling pathway	0.1950	101	4486	44	-0.28	0.034	1000	-1000	-0.09	-1000
amb2 Integrin signaling	0.1622	84	6921	82	-0.56	0.016	1000	-1000	-0.11	-1000
JNK signaling in the CD4+ TCR pathway	0.1583	82	1401	17	-0.42	0.016	1000	-1000	-0.085	-1000
IL4-mediated signaling events	0.1467	76	6996	91	-0.84	0.54	1000	-1000	-0.17	-1000
EGFR-dependent Endothelin signaling events	0.1390	72	1522	21	-0.67	0.016	1000	-1000	-0.11	-1000
Caspase cascade in apoptosis	0.1332	69	5167	74	-0.33	0.16	1000	-1000	-0.083	-1000
Aurora C signaling	0.1332	69	489	7	-0.4	0.012	1000	-1000	-0.06	-1000
VEGFR1 specific signals	0.1332	69	3897	56	-0.47	0.046	1000	-1000	-0.12	-1000
Glypican 2 network	0.1313	68	272	4	-0.12	-1000	1000	-1000	-0.051	-1000
HIF-2-alpha transcription factor network	0.1274	66	2841	43	-0.76	0.34	1000	-1000	-0.11	-1000
Syndecan-1-mediated signaling events	0.1236	64	2186	34	-0.42	0.016	1000	-1000	-0.11	-1000
IL23-mediated signaling events	0.1139	59	3584	60	-0.4	0.021	1000	-1000	-0.19	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1139	59	1958	33	-0.83	0.016	1000	-1000	-0.085	-1000
BMP receptor signaling	0.1120	58	4741	81	-0.7	0.016	1000	-1000	-0.13	-1000
Signaling events mediated by the Hedgehog family	0.0927	48	2537	52	-0.44	0.12	1000	-1000	-0.13	-1000
Fc-epsilon receptor I signaling in mast cells	0.0849	44	4343	97	-0.32	0.04	1000	-1000	-0.13	-1000
IL27-mediated signaling events	0.0811	42	2144	51	-0.61	0.078	1000	-1000	-0.11	-1000
Effects of Botulinum toxin	0.0792	41	1072	26	-0.37	0.016	1000	-1000	-0.087	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0792	41	2813	68	-0.55	0.064	1000	-1000	-0.18	-1000
Ephrin A reverse signaling	0.0753	39	277	7	-0.057	0	1000	-1000	-0.043	-1000
Arf6 signaling events	0.0714	37	2354	62	-0.67	0.016	1000	-1000	-0.09	-1000
p75(NTR)-mediated signaling	0.0714	37	4734	125	-0.42	0.016	1000	-1000	-0.15	-1000
Calcium signaling in the CD4+ TCR pathway	0.0714	37	1175	31	-0.46	0.016	1000	-1000	-0.15	-1000
IL2 signaling events mediated by STAT5	0.0656	34	760	22	-0.44	0.038	1000	-1000	-0.073	-1000
BCR signaling pathway	0.0656	34	3439	99	-0.34	0.035	1000	-1000	-0.13	-1000
LPA4-mediated signaling events	0.0637	33	402	12	-0.16	0.026	1000	-1000	-0.035	-1000
IL2 signaling events mediated by PI3K	0.0637	33	1948	58	-0.44	0.031	1000	-1000	-0.12	-1000
Coregulation of Androgen receptor activity	0.0579	30	2287	76	-0.92	0.033	1000	-1000	-0.071	-1000
PLK1 signaling events	0.0579	30	2603	85	-0.38	0.016	1000	-1000	-0.086	-1000
Glucocorticoid receptor regulatory network	0.0560	29	3405	114	-0.41	0.16	1000	-1000	-0.1	-1000
S1P1 pathway	0.0560	29	1056	36	-0.38	0.018	1000	-1000	-0.1	-1000
IL6-mediated signaling events	0.0560	29	2226	75	-0.28	0.076	1000	-1000	-0.12	-1000
Regulation of Telomerase	0.0560	29	2998	102	-0.67	0.051	1000	-1000	-0.15	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0541	28	1516	54	-0.66	0.031	1000	-1000	-0.13	-1000
Integrins in angiogenesis	0.0502	26	2264	84	-0.38	0.039	1000	-1000	-0.14	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0483	25	1965	78	-0.32	0.045	1000	-1000	-0.1	-1000
Aurora A signaling	0.0463	24	1458	60	-0.24	0.053	1000	-1000	-0.089	-1000
Visual signal transduction: Rods	0.0463	24	1253	52	-0.29	0.016	1000	-1000	-0.12	-1000
Reelin signaling pathway	0.0444	23	1296	56	-0.24	0.016	1000	-1000	-0.11	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0444	23	2043	88	-0.32	0.074	1000	-1000	-0.14	-1000
Signaling events mediated by PTP1B	0.0425	22	1725	76	-0.67	0.049	1000	-1000	-0.11	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0425	22	1000	45	-0.58	0.061	1000	-1000	-0.12	-1000
Syndecan-2-mediated signaling events	0.0386	20	1415	69	-0.56	0.054	1000	-1000	-0.089	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0386	20	2465	120	-0.17	0.14	1000	-1000	-0.12	-1000
Endothelins	0.0367	19	1908	96	-0.35	0.088	1000	-1000	-0.12	-1000
Regulation of nuclear SMAD2/3 signaling	0.0328	17	2410	136	-0.45	0.1	1000	-1000	-0.11	-1000
EPO signaling pathway	0.0328	17	975	55	-0.29	0.018	1000	-1000	-0.15	-1000
Wnt signaling	0.0328	17	123	7	-0.07	0.016	1000	-1000	-0.077	-1000
Thromboxane A2 receptor signaling	0.0309	16	1730	105	-0.67	0.066	1000	-1000	-0.1	-1000
Presenilin action in Notch and Wnt signaling	0.0309	16	1011	61	-0.19	0.093	1000	-1000	-0.11	-1000
S1P3 pathway	0.0309	16	698	42	-0.38	0.062	1000	-1000	-0.084	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0290	15	590	37	-0.3	0.026	1000	-1000	-0.12	-1000
FoxO family signaling	0.0290	15	980	64	-0.57	0.12	1000	-1000	-0.1	-1000
LPA receptor mediated events	0.0290	15	1619	102	-0.4	0.061	1000	-1000	-0.12	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0270	14	402	28	-0.13	0.025	1000	-1000	-0.086	-1000
PLK2 and PLK4 events	0.0270	14	42	3	-0.015	0.011	1000	-1000	-0.03	-1000
Ceramide signaling pathway	0.0270	14	1134	76	-0.67	0.23	1000	-1000	-0.099	-1000
Canonical Wnt signaling pathway	0.0270	14	727	51	-0.19	0.096	1000	-1000	-0.086	-1000
FAS signaling pathway (CD95)	0.0251	13	638	47	-0.43	0.028	1000	-1000	-0.069	-1000
Class I PI3K signaling events	0.0251	13	998	73	-0.46	0.036	1000	-1000	-0.11	-1000
E-cadherin signaling events	0.0251	13	68	5	-0.023	0.016	1000	-1000	-0.07	-1000
IFN-gamma pathway	0.0232	12	869	68	-0.38	0.017	1000	-1000	-0.14	-1000
Nongenotropic Androgen signaling	0.0232	12	637	52	-0.18	0.071	1000	-1000	-0.087	-1000
Regulation of Androgen receptor activity	0.0232	12	896	70	-0.96	0.04	1000	-1000	-0.11	-1000
ErbB4 signaling events	0.0212	11	818	69	-0.18	0.1	1000	-1000	-0.12	-1000
S1P5 pathway	0.0212	11	187	17	-0.13	0.045	1000	-1000	-0.081	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0212	11	1454	125	-0.39	0.044	1000	-1000	-0.15	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0212	11	845	74	-0.67	0.099	1000	-1000	-0.14	-1000
S1P4 pathway	0.0193	10	265	25	-0.13	0.035	1000	-1000	-0.076	-1000
Visual signal transduction: Cones	0.0174	9	355	38	-0.041	0.016	1000	-1000	-0.096	-1000
a4b1 and a4b7 Integrin signaling	0.0174	9	45	5	-0.019	0.016	1000	-1000	-0.053	-1000
Noncanonical Wnt signaling pathway	0.0154	8	213	26	-0.11	0.016	1000	-1000	-0.13	-1000
Signaling events regulated by Ret tyrosine kinase	0.0154	8	667	82	-0.064	0.027	1000	-1000	-0.12	-1000
TCGA08_rtk_signaling	0.0154	8	232	26	-0.28	0.041	1000	-1000	-0.036	-1000
Canonical NF-kappaB pathway	0.0116	6	268	39	-0.19	0.075	1000	-1000	-0.12	-1000
Signaling events mediated by HDAC Class III	0.0116	6	240	40	-0.059	0.033	1000	-1000	-0.063	-1000
IL1-mediated signaling events	0.0116	6	385	62	-0.091	0.06	1000	-1000	-0.14	-1000
Signaling events mediated by PRL	0.0116	6	231	34	-0.056	0.046	1000	-1000	-0.088	-1000
Class IB PI3K non-lipid kinase events	0.0116	6	18	3	-0.006	0.006	1000	-1000	-0.022	-1000
p38 MAPK signaling pathway	0.0116	6	270	44	-0.1	0.049	1000	-1000	-0.089	-1000
ErbB2/ErbB3 signaling events	0.0097	5	382	65	-0.13	0.059	1000	-1000	-0.11	-1000
Insulin-mediated glucose transport	0.0097	5	183	32	-0.086	0.067	1000	-1000	-0.095	-1000
Ephrin B reverse signaling	0.0097	5	279	48	-0.027	0.032	1000	-1000	-0.11	-1000
Signaling mediated by p38-gamma and p38-delta	0.0097	5	82	15	0	0.037	1000	-1000	-0.05	-1000
Syndecan-3-mediated signaling events	0.0097	5	205	35	-0.04	0.016	1000	-1000	-0.11	-1000
E-cadherin signaling in the nascent adherens junction	0.0097	5	391	76	-0.026	0.068	1000	-1000	-0.12	-1000
Arf6 trafficking events	0.0097	5	397	71	-0.12	0.058	1000	-1000	-0.1	-1000
Ras signaling in the CD4+ TCR pathway	0.0097	5	85	17	-0.037	0.055	1000	-1000	-0.068	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0077	4	368	85	-0.037	0.079	1000	-1000	-0.11	-1000
Arf6 downstream pathway	0.0077	4	214	43	-0.033	0.033	1000	-1000	-0.059	-1000
Paxillin-dependent events mediated by a4b1	0.0077	4	146	36	-0.026	0.031	1000	-1000	-0.1	-1000
EPHB forward signaling	0.0077	4	360	85	-0.074	0.07	1000	-1000	-0.14	-1000
Plasma membrane estrogen receptor signaling	0.0077	4	345	86	-0.17	0.072	1000	-1000	-0.12	-1000
BARD1 signaling events	0.0058	3	218	57	-0.17	0.043	1000	-1000	-0.1	-1000
Cellular roles of Anthrax toxin	0.0058	3	119	39	-0.022	0.027	1000	-1000	-0.05	-1000
E-cadherin signaling in keratinocytes	0.0058	3	162	43	-0.29	0.054	1000	-1000	-0.12	-1000
Osteopontin-mediated events	0.0039	2	113	38	-0.03	0.099	1000	-1000	-0.15	-1000
Hedgehog signaling events mediated by Gli proteins	0.0039	2	130	65	-0.062	0.093	1000	-1000	-0.093	-1000
ceramide signaling pathway	0.0039	2	126	49	-0.12	0.054	1000	-1000	-0.071	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0039	2	128	52	-0.031	0.093	1000	-1000	-0.096	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0039	2	176	83	-0.086	0.081	1000	-1000	-0.11	-1000
Retinoic acid receptors-mediated signaling	0.0039	2	122	58	-0.026	0.063	1000	-1000	-0.11	-1000
Regulation of p38-alpha and p38-beta	0.0039	2	148	54	-0.041	0.073	1000	-1000	-0.083	-1000
Insulin Pathway	0.0039	2	207	74	-0.034	0.055	1000	-1000	-0.14	-1000
PDGFR-beta signaling pathway	0.0039	2	272	97	-0.057	0.087	1000	-1000	-0.13	-1000
Signaling events mediated by HDAC Class II	0.0019	1	121	75	-0.027	0.051	1000	-1000	-0.095	-1000
Circadian rhythm pathway	0.0019	1	33	22	-0.019	0.064	1000	-1000	-0.095	-1000
mTOR signaling pathway	0.0019	1	70	53	-0.008	0.044	1000	-1000	-0.093	-1000
Class I PI3K signaling events mediated by Akt	0.0019	1	104	68	-0.086	0.06	1000	-1000	-0.099	-1000
Signaling events mediated by HDAC Class I	0.0019	1	202	104	-0.029	0.064	1000	-1000	-0.11	-1000
Atypical NF-kappaB pathway	0.0019	1	52	31	-0.021	0.037	1000	-1000	-0.11	-1000
Signaling mediated by p38-alpha and p38-beta	0.0019	1	57	44	-0.043	0.051	1000	-1000	-0.082	-1000
IGF1 pathway	0.0019	1	92	57	-0.065	0.071	1000	-1000	-0.14	-1000
Alternative NF-kappaB pathway	0.0019	1	14	13	-0.005	0.016	1000	-1000	-0.091	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	2	23	-0.001	0.062	1000	-1000	-0.096	-1000
Nectin adhesion pathway	0.0000	0	61	63	-0.015	0.08	1000	-1000	-0.12	-1000
TRAIL signaling pathway	0.0000	0	29	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	-0.081	-1000
Rapid glucocorticoid signaling	0.0000	0	12	20	-0.005	0.016	1000	-1000	-0.07	-1000
Arf1 pathway	0.0000	0	31	54	-0.01	0.043	1000	-1000	-0.071	-1000
Total	NA	4156	218451	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	0.093	-10000	0	-0.87	6	6
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.84	0.16	-10000	0	-0.88	499	499
CCND2	0.18	0.048	0.19	498	-10000	0	498
RB1	-0.2	0.05	-10000	0	-0.21	498	498
CDK4	0.22	0.051	0.22	498	-10000	0	498
CDK6	0.2	0.054	0.21	498	-0.18	1	499
G1/S progression	0.2	0.053	0.21	498	-10000	0	498

×

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	-0.98	0.53	-9999	-1.4	303	303
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.91	309	309
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.98	0.53	-9999	-1.3	318	318
AP1	-0.014	0.088	-9999	-0.56	13	13
ABCG2	-0.98	0.53	-9999	-1.4	303	303
HIF1A	-0.11	0.068	-9999	-0.89	2	2
TFF3	-0.99	0.53	-9999	-1.4	304	304
GATA2	0	0.12	-9999	-0.74	12	12
AKT1	-0.094	0.052	-9999	-10000	0	0
response to hypoxia	-0.13	0.057	-9999	-10000	0	0
MCL1	-0.98	0.53	-9999	-1.4	294	294
NDRG1	-0.98	0.53	-9999	-1.4	298	298
SERPINE1	-1	0.56	-9999	-1.4	319	319
FECH	-0.98	0.53	-9999	-1.4	302	302
FURIN	-0.98	0.53	-9999	-1.4	302	302
NCOA2	-0.002	0.099	-9999	-0.75	9	9
EP300	-0.1	0.074	-9999	-0.36	6	6
HMOX1	-1	0.54	-9999	-1.4	305	305
BHLHE40	-0.98	0.53	-9999	-1.4	299	299
BHLHE41	-1.1	0.58	-9999	-1.5	320	320
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.079	0.056	-9999	-0.6	2	2
ENG	-0.059	0.062	-9999	-10000	0	0
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.98	0.53	-9999	-1.4	299	299
ABCB1	-0.3	0.42	-9999	-1.3	68	68
TFRC	-0.98	0.53	-9999	-1.4	294	294
CXCR4	-1.1	0.59	-9999	-1.5	321	321
TF	-1	0.58	-9999	-1.4	308	308
CITED2	-0.98	0.53	-9999	-1.4	294	294
HIF1A/ARNT	-1.3	0.85	-9999	-1.7	340	340
LDHA	-0.086	0.063	-9999	-0.86	2	2
ETS1	-0.98	0.53	-9999	-1.4	302	302
PGK1	-0.98	0.53	-9999	-1.4	299	299
NOS2	-0.99	0.53	-9999	-1.4	296	296
ITGB2	-1	0.56	-9999	-1.4	323	323
ALDOA	-0.98	0.53	-9999	-1.4	294	294
Cbp/p300/CITED2	-0.98	0.53	-9999	-1.4	295	295
FOS	-0.003	0.12	-9999	-0.75	13	13
HK2	-1.2	0.58	-9999	-1.5	383	383
SP1	0.021	0.029	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.1	10	10
HK1	-0.98	0.53	-9999	-1.3	317	317
NPM1	-0.98	0.53	-9999	-1.4	294	294
EGLN1	-0.98	0.53	-9999	-1.4	297	297
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.98	0.53	-9999	-1.4	303	303
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.091	0.16	-9999	-0.8	18	18
IGFBP1	-1	0.57	-9999	-1.4	309	309
VEGFA	-0.78	0.41	-9999	-1.2	235	235
HIF1A/JAB1	-0.055	0.047	-9999	-0.7	2	2
CP	-1.2	0.58	-9999	-1.5	378	378
CXCL12	-0.99	0.53	-9999	-1.4	308	308
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.98	0.53	-9999	-1.4	294	294
EGLN3	-1.3	0.51	-9999	-1.5	402	402
CA9	-1.3	0.47	-9999	-1.5	414	414
TERT	-1	0.55	-9999	-1.4	317	317
ENO1	-0.98	0.53	-9999	-1.4	298	298
PFKL	-0.98	0.53	-9999	-1.4	299	299
NCOA1	0.015	0.003	-9999	-10000	0	0
ADM	-1.1	0.56	-9999	-1.4	317	317
ARNT	-0.1	0.046	-9999	-10000	0	0
HNF4A	-0.045	0.21	-9999	-0.75	44	44
ADFP	-0.99	0.52	-9999	-1.3	334	334
SLC2A1	-0.63	0.33	-9999	-0.97	171	171
LEP	-1	0.54	-9999	-1.4	319	319
HIF1A/ARNT/Cbp/p300	-0.71	0.34	-9999	-0.93	310	310
EPO	-0.61	0.39	-9999	-1.1	177	177
CREBBP	-0.099	0.072	-9999	-0.35	3	3
HIF1A/ARNT/Cbp/p300/HDAC7	-0.75	0.38	-9999	-1	296	296
PFKFB3	-0.98	0.53	-9999	-1.3	317	317
NT5E	-0.98	0.53	-9999	-1.4	299	299

×

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	402	-10000	0	402
KIRREL	-0.055	0.11	-10000	0	-0.82	9	9
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.49	0.26	-10000	0	-0.62	402	402
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	224	224
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.41	0.26	-10000	0	-0.66	224	224
FYN	-0.5	0.3	-10000	0	-0.8	224	224
mol:Ca2+	-0.52	0.3	-10000	0	-0.83	224	224
mol:DAG	-0.53	0.31	-10000	0	-0.83	224	224
NPHS2	-0.41	0.38	-10000	0	-0.81	248	248
mol:IP3	-0.53	0.31	-10000	0	-0.83	224	224
regulation of endocytosis	-0.47	0.28	-10000	0	-0.75	224	224
Nephrin/NEPH1/podocin/Cholesterol	-0.54	0.31	-10000	0	-0.85	225	225
establishment of cell polarity	-0.48	0.26	-10000	0	-0.62	402	402
Nephrin/NEPH1/podocin/NCK1-2	-0.49	0.29	-10000	0	-0.78	224	224
Nephrin/NEPH1/beta Arrestin2	-0.48	0.28	-10000	0	-0.76	224	224
NPHS1	-0.61	0.33	-10000	0	-0.78	400	400
Nephrin/NEPH1/podocin	-0.51	0.3	-10000	0	-0.8	224	224
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.014	0.033	-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	224	224
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.53	0.31	-10000	0	-0.84	224	224
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	224	224
cytoskeleton organization	-0.53	0.32	-10000	0	-0.85	224	224
Nephrin/NEPH1	-0.36	0.2	-10000	0	-0.47	402	402
Nephrin/NEPH1/ZO-1	-0.39	0.22	-10000	0	-0.55	225	225

×

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	-0.69	231	231
FYN	-0.41	0.5	-10000	0	-0.92	237	237
LAT/GRAP2/SLP76	-0.36	0.39	-10000	0	-0.74	247	247
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.25	0.29	-10000	0	-0.53	245	245
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.08	0.072	-10000	0	-0.19	78	78
MAP3K8	0.012	0.055	-10000	0	-0.86	2	2
mol:Ca2+	-0.11	0.045	-10000	0	-0.14	291	291
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	250	250
TRPV6	-0.66	0.26	-10000	0	-0.76	448	448
CD28	-0.058	0.23	-10000	0	-0.87	39	39
SHC1	-0.44	0.49	-10000	0	-0.93	244	244
receptor internalization	-0.52	0.56	-10000	0	-1.1	248	248
PRF1	-0.49	0.6	-10000	0	-1.1	242	242
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	222	222
LAT	-0.5	0.53	-10000	0	-1	257	257
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	234	234
CD3E	-0.34	0.44	-10000	0	-0.88	208	208
CD3G	-0.33	0.43	-10000	0	-0.87	202	202
RASGRP2	-0.023	0.029	-10000	0	-0.14	2	2
RASGRP1	-0.23	0.27	-10000	0	-0.5	236	236
HLA-A	0.005	0.056	-10000	0	-0.88	2	2
RASSF5	-0.011	0.15	-10000	0	-0.86	16	16
RAP1A/GTP/RAPL	-0.018	0.1	-10000	0	-0.59	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	104	104
PRKCA	-0.14	0.17	-10000	0	-0.31	213	213
GRAP2	-0.043	0.22	-10000	0	-0.86	35	35
mol:IP3	-0.16	0.34	0.26	168	-0.5	230	398
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.53	0.63	-10000	0	-1.1	249	249
ORAI1	0.33	0.13	0.38	447	-10000	0	447
CSK	-0.46	0.51	-10000	0	-0.97	243	243
B7 family/CD28	-0.52	0.52	-10000	0	-1	243	243
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	250	250
PTPN6	-0.44	0.52	-10000	0	-0.99	234	234
VAV1	-0.49	0.53	-10000	0	-1	253	253
Monovalent TCR/CD3	-0.46	0.53	-10000	0	-0.99	238	238
CBL	0.014	0.033	-10000	0	-0.75	1	1
LCK	-0.44	0.53	-10000	0	-0.98	240	240
PAG1	-0.46	0.51	-10000	0	-0.97	244	244
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.53	0.63	-10000	0	-1.2	242	242
CD80	-0.18	0.37	-10000	0	-0.87	115	115
CD86	-0.13	0.32	-10000	0	-0.87	81	81
PDK1/CARD11/BCL10/MALT1	-0.18	0.17	-10000	0	-0.36	186	186
HRAS	0.014	0.039	-10000	0	-0.86	1	1
GO:0035030	-0.36	0.42	-10000	0	-0.77	243	243
CD8A	-0.39	0.44	-10000	0	-0.87	234	234
CD8B	-0.31	0.43	-10000	0	-0.88	186	186
PTPRC	-0.086	0.27	-10000	0	-0.87	56	56
PDK1/PKC theta	-0.32	0.36	-10000	0	-0.68	242	242
CSK/PAG1	-0.44	0.49	-10000	0	-0.94	240	240
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.042	-10000	0	-0.68	2	2
GRAP2/SLP76	-0.44	0.44	-10000	0	-0.88	244	244
STIM1	0.17	0.065	-10000	0	-10000	0	0
RAS family/GTP	-0.064	0.11	-10000	0	-0.25	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.59	0.65	-10000	0	-1.2	248	248
mol:DAG	-0.2	0.26	-10000	0	-0.46	236	236
RAP1A/GDP	-0.014	0.036	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	171	171
cytotoxic T cell degranulation	-0.45	0.55	-10000	0	-0.99	242	242
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.32	0.35	-10000	0	-0.65	250	250
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.27	0.44	0.3	112	-0.7	236	348
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.46	0.44	-10000	0	-0.86	281	281
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.38	0.35	-10000	0	-0.72	248	248
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.5	0.57	-10000	0	-1.1	240	240
CARD11	-0.17	0.36	-10000	0	-0.86	110	110
PRKCB	-0.14	0.17	-10000	0	-0.31	214	214
PRKCE	-0.14	0.17	-10000	0	-0.31	213	213
PRKCQ	-0.39	0.42	-10000	0	-0.8	249	249
LCP2	-0.04	0.22	-10000	0	-0.86	33	33
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.2	0.24	-10000	0	-0.44	241	241
IKK complex	-0.028	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	175	175
PDPK1	-0.23	0.27	-10000	0	-0.5	235	235
TCR/CD3/MHC I/CD8/Fyn	-0.56	0.65	-10000	0	-1.2	239	239

×

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	499	499
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	0.061	0.32	499	-10000	0	499
MDM4	0.014	0.039	-10000	0	-0.86	1	1

×

Aurora B signaling

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
Condensin I complex	-0.24	0.32	-9999	-0.68	161	161
STMN1	-0.29	0.35	-9999	-0.66	243	243
Aurora B/RasGAP/Survivin	-0.41	0.48	-9999	-0.88	249	249
Chromosomal passenger complex/Cul3 protein complex	-0.17	0.23	-9999	-0.49	149	149
BIRC5	-0.26	0.41	-9999	-0.89	153	153
DES	-0.38	0.34	-9999	-0.59	308	308
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	244	244
Aurora B/TACC1	-0.26	0.3	-9999	-0.58	243	243
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	243	243
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.073	0.09	-9999	-0.17	106	106
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.41	0.5	-9999	-0.89	247	247
Cul3 protein complex	-0.016	0.085	-9999	-10000	0	0
KIF2C	-0.15	0.18	-9999	-0.34	198	198
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.38	0.44	-9999	-0.87	234	234
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	244	244
SEPT1	-0.096	0.29	-9999	-0.86	66	66
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.18	0.24	-9999	-0.44	224	224
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	243	243
AURKB	-0.4	0.44	-9999	-0.87	243	243
AURKC	0.012	0.055	-9999	-0.86	2	2
CDCA8	-0.025	0.17	-9999	-0.9	19	19
cytokinesis	-0.35	0.37	-9999	-0.75	208	208
Aurora B/Septin1	-0.36	0.42	-9999	-0.83	206	206
AURKA	0.002	0.095	-9999	-0.87	6	6
INCENP	0.008	0.009	-9999	-10000	0	0
KLHL13	-0.009	0.14	-9999	-0.75	17	17
BUB1	-0.37	0.44	-9999	-0.87	227	227
hSgo1/Aurora B/Survivin	-0.4	0.49	-9999	-0.86	250	250
EVI5	0.01	0.008	-9999	-10000	0	0
RhoA/GTP	-0.31	0.34	-9999	-0.72	188	188
SGOL1	-0.015	0.16	-9999	-0.86	18	18
CENPA	-0.29	0.35	-9999	-0.62	253	253
NCAPG	-0.28	0.42	-9999	-0.86	174	174
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	243	243
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	243	243
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.13	0.33	-9999	-0.86	87	87
NPM1	-0.22	0.24	-9999	-0.47	243	243
RASA1	0.014	0.033	-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	243	243
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.34	0.38	-9999	-0.78	198	198
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.22	0.24	-9999	-0.47	243	243
MYLK	-0.17	0.21	-9999	-0.39	243	243
KIF23	-0.007	0.11	-9999	-0.88	8	8
VIM	-0.35	0.4	-9999	-0.73	257	257
RACGAP1	0.004	0.055	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.22	0.24	-9999	-0.47	243	243
Chromosomal passenger complex	-0.35	0.41	-9999	-0.74	248	248
Chromosomal passenger complex/EVI5	-0.37	0.48	-9999	-0.94	182	182
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

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.46	0.39	-9999	-0.85	233	233
positive regulation of JNK cascade	-0.54	0.37	-9999	-0.84	281	281
Syndecan-4/ADAM12	-0.57	0.5	-9999	-1	257	257
CCL5	-0.36	0.44	-9999	-0.86	221	221
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.049	0.23	-9999	-0.86	38	38
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.37	0.37	-9999	-0.72	269	269
ADAM12	-0.22	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	235	235
Syndecan-4/CXCL12/CXCR4	-0.59	0.43	-9999	-0.94	281	281
Syndecan-4/Laminin alpha3	-0.47	0.39	-9999	-0.85	238	238
MDK	-0.05	0.23	-9999	-0.86	39	39
Syndecan-4/FZD7	-0.46	0.39	-9999	-0.84	234	234
Syndecan-4/Midkine	-0.5	0.42	-9999	-0.88	246	246
FZD7	0.014	0.033	-9999	-0.75	1	1
Syndecan-4/FGFR1/FGF	-0.44	0.34	-9999	-0.77	236	236
THBS1	0.011	0.058	-9999	-0.75	3	3
integrin-mediated signaling pathway	-0.45	0.36	-9999	-0.79	239	239
positive regulation of MAPKKK cascade	-0.54	0.37	-9999	-0.84	281	281
Syndecan-4/TACI	-0.5	0.42	-9999	-0.9	246	246
CXCR4	-0.29	0.42	-9999	-0.86	178	178
cell adhesion	-0.007	0.12	-9999	-0.51	14	14
Syndecan-4/Dynamin	-0.46	0.39	-9999	-0.85	233	233
Syndecan-4/TSP1	-0.47	0.39	-9999	-0.85	235	235
Syndecan-4/GIPC	-0.46	0.39	-9999	-0.84	234	234
Syndecan-4/RANTES	-0.65	0.46	-9999	-1	289	289
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.007	0.13	-9999	-0.75	15	15
LAMA3	0.004	0.1	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.066	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.47	0.39	-9999	-0.85	234	234
TFPI	0.001	0.11	-9999	-0.81	9	9
F2	-0.32	0.42	-9999	-0.87	194	194
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.67	38	38
positive regulation of cell adhesion	-0.45	0.38	-9999	-0.82	240	240
ACTN1	0.013	0.051	-9999	-0.8	2	2
TNC	-0.003	0.12	-9999	-0.75	13	13
Syndecan-4/CXCL12	-0.47	0.39	-9999	-0.85	238	238
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	0	0.11	-9999	-0.75	11	11
TNFRSF13B	-0.071	0.26	-9999	-0.86	50	50
FGF2	0.008	0.077	-9999	-0.77	5	5
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.47	0.39	-9999	-0.86	233	233
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.039	0.22	-9999	-0.83	38	38
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.045	-9999	-0.85	1	1
vasculogenesis	-0.44	0.36	-9999	-0.79	235	235
SDC4	-0.51	0.43	-9999	-0.93	233	233
Syndecan-4/Tenascin C	-0.47	0.39	-9999	-0.84	239	239
Syndecan-4/PI-4-5-P2/PKC alpha	-0.08	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.46	0.39	-9999	-0.85	233	233
MMP9	-0.4	0.44	-9999	-0.86	247	247
Rac1/GTP	-0.008	0.12	-9999	-0.53	14	14
cytoskeleton organization	-0.44	0.36	-9999	-0.8	233	233
GIPC1	0.014	0.033	-9999	-0.75	1	1
Syndecan-4/TFPI	-0.47	0.39	-9999	-0.85	237	237

×

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	111	111
PCK1	-0.94	0.71	-10000	0	-1.4	302	302
HNF4A	-0.58	0.58	-10000	0	-1.3	142	142
KCNJ11	-0.45	0.51	-10000	0	-1.3	103	103
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	161	161
NKX2-1	-0.057	0.21	0.58	1	-0.84	4	5
ACADM	-0.45	0.48	-10000	0	-1.1	124	124
TAT	-0.52	0.36	-10000	0	-0.97	144	144
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	331	331
PKLR	-0.5	0.56	-10000	0	-1.3	127	127
APOA1	-0.56	0.56	-10000	0	-1.3	142	142
CPT1C	-0.45	0.48	-10000	0	-1.2	108	108
ALAS1	-0.17	0.19	-10000	0	-10000	0	0
TFRC	-0.63	0.42	-10000	0	-1	202	202
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	-1.1	128	128
HMGCS1	-0.45	0.48	-10000	0	-1.2	115	115
NR3C1	0.003	0.065	-10000	0	-0.97	1	1
CPT1B	-0.46	0.5	-10000	0	-1.2	116	116
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	122	122
CREB1	-0.028	0.066	-10000	0	-10000	0	0
IGFBP1	-0.32	0.42	-10000	0	-1	119	119
PDX1	-0.19	0.22	-10000	0	-1	6	6
UCP2	-0.45	0.48	-10000	0	-1.2	116	116
ALDOB	-0.94	0.62	-10000	0	-1.2	398	398
AFP	-0.71	0.5	-10000	0	-0.97	319	319
BDH1	-0.6	0.57	-10000	0	-1.2	197	197
HADH	-0.44	0.49	-10000	0	-1.2	102	102
F2	-0.66	0.62	-10000	0	-1.3	192	192
HNF1A	-0.002	0.087	-10000	0	-0.79	5	5
G6PC	-0.81	0.66	-10000	0	-1.5	248	248
SLC2A2	-0.32	0.48	-10000	0	-1.7	47	47
INS	0.01	0.055	-10000	0	-10000	0	0
FOXA1	-0.37	0.39	-10000	0	-0.96	136	136
FOXA3	-0.61	0.37	-10000	0	-0.89	296	296
FOXA2	-0.52	0.57	-10000	0	-1.3	130	130
ABCC8	-0.44	0.49	-10000	0	-1.2	110	110
ALB	-1.2	0.49	-10000	0	-1.4	445	445

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.17	0.26	-10000	0	-0.65	70	70
TBX21	-0.55	0.68	-10000	0	-1.3	214	214
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	-0.91	159	159
GADD45B	-0.3	0.43	-10000	0	-0.83	143	143
IL12RB2	-0.11	0.31	-10000	0	-0.87	74	74
GADD45G	-0.31	0.43	-10000	0	-0.81	167	167
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	104	104
IFNG	-0.39	0.44	-10000	0	-0.86	237	237
STAT3 (dimer)	-0.37	0.47	-10000	0	-0.88	200	200
HLA-DRB5	-0.038	0.21	-10000	0	-0.86	32	32
FASLG	-0.61	0.7	-10000	0	-1.3	229	229
NF kappa B2 p52/RelB	-0.52	0.53	-10000	0	-1.1	219	219
CD4	0.001	0.12	-10000	0	-0.86	9	9
SOCS1	0.006	0.094	-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	234	234
CD3E	-0.34	0.43	-10000	0	-0.87	208	208
CD3G	-0.33	0.43	-10000	0	-0.87	202	202
IL12Rbeta2/JAK2	-0.085	0.25	-10000	0	-0.68	74	74
CCL3	-0.49	0.63	-10000	0	-1.2	196	196
CCL4	-0.5	0.66	-10000	0	-1.3	192	192
HLA-A	0.007	0.055	-10000	0	-0.86	2	2
IL18/IL18R	-0.13	0.3	-10000	0	-0.6	145	145
NOS2	-0.36	0.5	-10000	0	-0.95	171	171
IL12/IL12R/TYK2/JAK2/SPHK2	-0.16	0.26	-10000	0	-0.65	67	67
IL1R1	-0.45	0.59	-10000	0	-1.2	179	179
IL4	0.014	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.022	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.7	0.82	-10000	0	-1.4	258	258
RAB7A	-0.24	0.37	-10000	0	-0.78	53	53
lysosomal transport	-0.22	0.36	-10000	0	-0.73	56	56
FOS	-0.38	0.5	-10000	0	-0.95	200	200
STAT4 (dimer)	-0.41	0.53	-10000	0	-0.97	206	206
STAT5A (dimer)	-0.66	0.61	-10000	0	-1.2	248	248
GZMA	-0.57	0.7	-10000	0	-1.3	217	217
GZMB	-0.54	0.67	-10000	0	-1.3	205	205
HLX	-0.088	0.28	-10000	0	-0.86	61	61
LCK	-0.52	0.69	-10000	0	-1.2	217	217
TCR/CD3/MHC II/CD4	-0.38	0.47	-10000	0	-0.86	228	228
IL2/IL2R	-0.42	0.42	-10000	0	-0.71	306	306
MAPK14	-0.3	0.44	-10000	0	-0.82	162	162
CCR5	-0.45	0.59	-10000	0	-1.1	200	200
IL1B	0.002	0.096	-10000	0	-0.86	6	6
STAT6	-0.084	0.15	-10000	0	-10000	0	0
STAT4	-0.035	0.2	-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	0.033	-10000	0	-0.75	1	1
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.092	0.29	-10000	0	-0.89	60	60
CD8A	-0.38	0.44	-10000	0	-0.87	234	234
CD8B	-0.3	0.42	-10000	0	-0.87	186	186
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.16	0.26	0.64	70	-10000	0	70
IL2RB	-0.45	0.44	-10000	0	-0.86	272	272
proteasomal ubiquitin-dependent protein catabolic process	-0.36	0.47	-10000	0	-0.86	203	203
IL2RG	-0.042	0.22	-10000	0	-0.86	34	34
IL12	-0.07	0.24	-10000	0	-0.71	61	61
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	171	171
IL2	-0.007	0.12	-10000	0	-0.86	10	10
SPHK2	0.013	0.047	-10000	0	-0.75	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.046	-10000	0	-0.91	1	1
IL12/IL12R/TYK2/JAK2	-0.58	0.78	-10000	0	-1.4	220	220
MAP2K3	-0.31	0.44	-10000	0	-0.81	180	180
RIPK2	0.014	0.039	-10000	0	-0.86	1	1
MAP2K6	-0.31	0.44	-10000	0	-0.83	167	167
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.077	-10000	0	-0.86	4	4
IL18RAP	-0.21	0.39	-10000	0	-0.87	133	133
IL12Rbeta1/TYK2	-0.21	0.34	-10000	0	-0.72	159	159
EOMES	-0.3	0.37	-10000	0	-0.74	213	213
STAT1 (dimer)	-0.45	0.51	-10000	0	-0.96	233	233
T cell proliferation	-0.26	0.37	-10000	0	-0.67	178	178
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	-0.75	182	182
ATF2	-0.27	0.41	-10000	0	-0.78	137	137

×

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	-0.19	0.68	-10000	0	-1.2	122	122
PLK1	-0.1	0.41	-10000	0	-0.8	128	128
BIRC5	-0.14	0.43	-10000	0	-0.79	153	153
HSPA1B	-0.19	0.68	-10000	0	-1.2	118	118
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.2	0.68	-10000	0	-1.2	123	123
FOXM1	-0.37	0.99	-10000	0	-1.8	133	133
XRCC1	-0.19	0.68	-10000	0	-1.2	118	118
FOXM1B/p19	-0.5	0.49	0.51	1	-1.2	131	132
Cyclin D1/CDK4	-0.18	0.61	-10000	0	-1.1	117	117
CDC2	-0.22	0.72	-10000	0	-1.3	133	133
TGFA	-0.16	0.6	-10000	0	-1.1	114	114
SKP2	-0.19	0.68	-10000	0	-1.2	118	118
CCNE1	0.003	0.1	-10000	0	-0.88	7	7
CKS1B	-0.19	0.68	-10000	0	-1.2	122	122
RB1	-0.19	0.26	-10000	0	-0.69	93	93
FOXM1C/SP1	-0.28	0.78	-10000	0	-1.5	130	130
AURKB	-0.25	0.46	-10000	0	-0.74	243	243
CENPF	-0.21	0.72	-10000	0	-1.3	124	124
CDK4	0.02	0.022	-10000	0	-10000	0	0
MYC	-0.16	0.6	-10000	0	-1	121	121
CHEK2	0.038	0.063	-10000	0	-0.91	1	1
ONECUT1	-0.19	0.65	-10000	0	-1.2	122	122
CDKN2A	-0.82	0.17	-10000	0	-0.86	499	499
LAMA4	-0.28	0.69	-10000	0	-1.3	134	134
FOXM1B/HNF6	-0.28	0.79	-10000	0	-1.5	123	123
FOS	-0.2	0.69	-10000	0	-1.2	124	124
SP1	0.016	0.005	-10000	0	-10000	0	0
CDC25B	-0.19	0.68	-10000	0	-1.2	118	118
response to radiation	0.013	0.05	-10000	0	-10000	0	0
CENPB	-0.19	0.68	-10000	0	-1.2	121	121
CENPA	-0.28	0.78	-10000	0	-1.4	144	144
NEK2	-0.24	0.75	-10000	0	-1.4	129	129
HIST1H2BA	-0.2	0.68	-10000	0	-1.2	123	123
CCNA2	-0.16	0.36	-10000	0	-0.88	101	101
EP300	0.014	0.033	-10000	0	-0.75	1	1
CCNB1/CDK1	-0.28	0.81	-10000	0	-1.5	123	123
CCNB2	-0.24	0.76	-10000	0	-1.4	133	133
CCNB1	-0.21	0.72	-10000	0	-1.3	122	122
ETV5	-0.19	0.68	-10000	0	-1.2	121	121
ESR1	-0.19	0.68	-10000	0	-1.2	123	123
CCND1	-0.18	0.63	-10000	0	-1.1	118	118
GSK3A	0.036	0.041	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.082	0.28	-10000	0	-0.64	102	102
CDK2	0.015	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.015	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.42	0.58	-10000	0	-1.3	137	137
GAS1	-0.23	0.7	-10000	0	-1.2	132	132
MMP2	-0.19	0.68	-10000	0	-1.2	119	119
RB1/FOXM1C	-0.21	0.67	-10000	0	-1.2	122	122
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.053	-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	-0.75	15	15
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.56	111	111
SMAD2	0.045	0.021	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.021	-10000	0	-0.49	1	1
GPC1/Laminin alpha1	-0.017	0.098	-10000	0	-0.57	16	16
TDGF1	-0.56	0.32	-10000	0	-0.75	390	390
CRIPTO/GPC1	-0.42	0.24	-10000	0	-0.56	390	390
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	390	390
FLT1	0.007	0.086	-10000	0	-0.86	5	5
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.021	-10000	0	-10000	0	0
SERPINC1	-0.054	0.22	-10000	0	-0.76	45	45
FYN	-0.35	0.22	-10000	0	-0.48	390	390
FGR	-0.35	0.22	-10000	0	-0.48	390	390
positive regulation of MAPKKK cascade	-0.36	0.24	-10000	0	-0.73	52	52
SLIT2	-0.15	0.31	-10000	0	-0.75	110	110
GPC1/NRG	-0.018	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	-0.59	234	234
LYN	-0.35	0.22	-10000	0	-0.48	390	390
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	0.033	0.74	1	-10000	0	1
SRC	-0.35	0.22	-10000	0	-0.48	390	390
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.062	0.24	-10000	0	-0.86	43	43
GPC1	0.014	0.033	-10000	0	-0.75	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.38	0.44	-10000	0	-0.86	233	233
BLK	-0.39	0.26	-10000	0	-0.52	395	395
HCK	-0.38	0.24	-10000	0	-0.5	400	400
FGF2	0.008	0.077	-10000	0	-0.77	5	5
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.007	0.086	-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	-0.051	0.16	-10000	0	-0.58	46	46
PLA2G2A/GPC1	-0.056	0.18	-10000	0	-0.66	44	44
LCK	-0.37	0.24	-10000	0	-0.5	398	398
neuron differentiation	-0.018	0.099	-10000	0	-0.56	17	17
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.033	-10000	0	-0.75	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

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	-0.74	199	199
PDGF/PDGFRA/CRKL	-0.21	0.26	-9999	-0.54	199	199
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	202	202
AP1	-0.16	0.24	-9999	-1.2	13	13
mol:IP3	-0.19	0.29	-9999	-0.56	199	199
PLCG1	-0.19	0.29	-9999	-0.56	199	199
PDGF/PDGFRA/alphaV Integrin	-0.21	0.26	-9999	-0.54	199	199
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	199	199
CAV3	-0.001	0.066	-9999	-0.86	3	3
CAV1	-0.047	0.23	-9999	-0.86	37	37
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/Shf	-0.21	0.26	-9999	-0.54	200	200
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	199	199
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
mol:DAG	-0.19	0.29	-9999	-0.56	199	199
PDGF/PDGFRA	-0.27	0.37	-9999	-0.74	199	199
actin cytoskeleton reorganization	-0.21	0.26	-9999	-0.54	199	199
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	200	200
PDGF/PDGFRA/Crk/C3G	-0.18	0.22	-9999	-0.46	199	199
JAK1	-0.19	0.28	-9999	-0.54	199	199
ELK1/SRF	-0.15	0.19	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.033	-9999	-0.75	1	1
CSNK2A1	0.017	0.022	-9999	-10000	0	0
GO:0007205	-0.2	0.3	-9999	-0.57	199	199
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	-0.54	199	199
PDGF/PDGFRA/Caveolin-1	-0.26	0.3	-9999	-0.58	228	228
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.26	-9999	-0.49	199	199
PIK3CA	0.014	0.033	-9999	-0.75	1	1
PDGF/PDGFRA/Crk	-0.21	0.26	-9999	-0.54	199	199
JAK-STAT cascade	-0.19	0.28	-9999	-0.54	199	199
cell proliferation	-0.21	0.26	-9999	-0.54	200	200

×

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	0.29	-9999	-0.68	105	105
alphaM/beta2 Integrin/GPIbA	-0.13	0.28	-9999	-0.68	101	101
alphaM/beta2 Integrin/proMMP-9	-0.4	0.43	-9999	-0.75	275	275
PLAUR	-0.028	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	-0.68	100	100
AGER	-0.14	0.33	-9999	-0.86	90	90
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.042	0.22	-9999	-0.86	34	34
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.23	0.34	-9999	-0.66	167	167
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	247	247
CYR61	0.007	0.082	-9999	-0.75	6	6
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.25	0.2	-9999	-0.56	114	114
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.018	0.16	-9999	-0.74	23	23
MYH2	-0.34	0.26	-9999	-0.64	186	186
MST1R	0.005	0.092	-9999	-0.78	7	7
leukocyte activation during inflammatory response	-0.28	0.35	-9999	-0.63	220	220
APOB	-0.27	0.41	-9999	-0.86	169	169
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.006	0.092	-9999	-0.84	6	6
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.033	-9999	-0.75	1	1
alphaM/beta2 Integrin/CTGF	-0.14	0.29	-9999	-0.68	105	105
alphaM/beta2 Integrin	-0.3	0.25	-9999	-0.54	222	222
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	0.25	-9999	-0.53	222	222
cell adhesion	-0.13	0.28	-9999	-0.67	101	101
NFKB1	-0.17	0.37	-9999	-0.95	62	62
THY1	0.014	0.033	-9999	-0.75	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.2	0.28	-9999	-0.59	170	170
alphaM/beta2 Integrin/LRP/tPA	-0.13	0.27	-9999	-0.63	102	102
IL6	-0.2	0.41	-9999	-0.91	99	99
ITGB2	-0.15	0.34	-9999	-0.86	98	98
elevation of cytosolic calcium ion concentration	-0.15	0.3	-9999	-0.64	120	120
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.26	-9999	-0.62	100	100
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.14	0.28	-9999	-0.85	41	41
alphaM/beta2 Integrin/uPA/Plg	-0.35	0.34	-9999	-0.77	138	138
RhoA/GTP	-0.37	0.27	-9999	-0.68	185	185
positive regulation of phagocytosis	-0.25	0.27	-9999	-0.69	111	111
Ron/MSP	-0.018	0.1	-9999	-0.62	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.15	0.3	-9999	-0.64	120	120
alphaM/beta2 Integrin/uPAR	-0.16	0.32	-9999	-0.71	116	116
PLAU	0.003	0.1	-9999	-0.75	9	9
PLAT	-0.005	0.12	-9999	-0.75	14	14
actin filament polymerization	-0.33	0.24	-9999	-0.61	186	186
MST1	0.002	0.11	-9999	-0.85	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.28	0.36	-9999	-0.64	220	220
TNF	-0.15	0.34	-9999	-0.84	66	66
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.14	0.28	-9999	-0.66	109	109
fibrinolysis	-0.35	0.34	-9999	-0.76	138	138
HCK	-0.032	0.2	-9999	-0.86	28	28
dendritic cell antigen processing and presentation	-0.3	0.25	-9999	-0.53	222	222
VTN	-0.1	0.28	-9999	-0.76	79	79
alphaM/beta2 Integrin/CYR61	-0.14	0.28	-9999	-0.67	106	106
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	-0.7	277	277
FN1	-0.049	0.23	-9999	-0.86	38	38
alphaM/beta2 Integrin/Thy1	-0.13	0.28	-9999	-0.68	101	101
MPO	-0.014	0.16	-9999	-0.86	17	17
KNG1	-0.56	0.33	-9999	-0.75	386	386
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.33	0.26	-9999	-0.64	176	176
ELA2	0	0	-9999	-10000	0	0
PLG	-0.38	0.38	-9999	-0.75	269	269
CTGF	0.005	0.088	-9999	-0.75	7	7
alphaM/beta2 Integrin/Hck	-0.16	0.35	-9999	-0.79	104	104
ITGAM	-0.021	0.17	-9999	-0.86	21	21
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.17	0.34	-9999	-0.75	109	109
HP	-0.2	0.38	-9999	-0.86	129	129
leukocyte adhesion	-0.18	0.27	-9999	-0.78	60	60
SELP	-0.018	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	-0.42	0.54	-9999	-0.9	238	238
MAP4K1	-0.34	0.43	-9999	-0.86	211	211
MAP3K8	0.012	0.055	-9999	-0.86	2	2
PRKCB	0.008	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	121	121
JUN	0.001	0.08	-9999	-0.56	5	5
MAP3K7	-0.15	0.3	-9999	-0.62	121	121
GRAP2	-0.043	0.22	-9999	-0.86	35	35
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.14	0.29	-9999	-0.59	121	121
LAT	-0.23	0.4	-9999	-0.86	145	145
LCP2	-0.04	0.22	-9999	-0.86	33	33
MAPK8	-0.01	0.084	-9999	-0.6	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.2	0.29	-9999	-0.67	121	121
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.39	0.51	-9999	-0.85	238	238

×

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	107	107
STAT6 (cleaved dimer)	-0.58	0.49	-10000	0	-1.1	181	181
IGHG1	-0.17	0.19	-10000	0	-0.66	12	12
IGHG3	-0.48	0.46	-10000	0	-1.1	143	143
AKT1	-0.28	0.33	-10000	0	-0.84	83	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.24	0.32	-10000	0	-0.83	83	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.79	68	68
THY1	-0.48	0.48	-10000	0	-1.2	113	113
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	117	117
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.79	67	67
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.009	0.077	-10000	0	-0.86	4	4
SOCS5	0.027	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.48	-10000	0	-1.2	155	155
SOCS1	-0.33	0.34	-10000	0	-0.8	81	81
SOCS3	-0.3	0.34	-10000	0	-0.92	67	67
FCER2	-0.41	0.44	-10000	0	-1.1	84	84
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.5	0.5	-10000	0	-1.2	113	113
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.28	-10000	0	-0.77	58	58
T cell proliferation	-0.5	0.51	-10000	0	-1.2	131	131
IL4R/JAK1	-0.48	0.47	-10000	0	-1.2	111	111
EGR2	-0.49	0.5	-10000	0	-1.2	116	116
JAK2	0.007	0.023	-10000	0	-10000	0	0
JAK3	-0.16	0.36	-10000	0	-0.87	105	105
PIK3R1	0.014	0.033	-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	112	112
IL4R	-0.51	0.51	-10000	0	-1.2	112	112
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.55	0.56	-10000	0	-1.3	136	136
IL13RA1	0.007	0.023	-10000	0	-10000	0	0
IRF4	-0.27	0.42	-10000	0	-0.99	116	116
ARG1	-0.18	0.26	-10000	0	-0.76	50	50
CBL	-0.36	0.4	-10000	0	-0.96	110	110
GTF3A	0.011	0.029	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
IL13RA1/JAK2	-0.006	0.043	-10000	0	-10000	0	0
IRF4/BCL6	-0.27	0.38	-10000	0	-0.93	114	114
CD40LG	-0.074	0.28	-10000	0	-0.92	53	53
MAPK14	-0.35	0.39	-10000	0	-0.99	97	97
mitosis	-0.26	0.31	-10000	0	-0.79	82	82
STAT6	-0.55	0.56	-10000	0	-1.3	127	127
SPI1	-0.098	0.3	-10000	0	-0.86	70	70
RPS6KB1	-0.24	0.3	-10000	0	-0.78	70	70
STAT6 (dimer)	-0.55	0.56	-10000	0	-1.3	127	127
STAT6 (dimer)/PARP14	-0.51	0.51	-10000	0	-1.2	126	126
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	95	95
FRAP1	-0.28	0.33	-10000	0	-0.84	83	83
LTA	-0.6	0.56	-10000	0	-1.3	161	161
FES	0.013	0.047	-10000	0	-0.75	2	2
T-helper 1 cell differentiation	0.54	0.54	1.3	127	-10000	0	127
CCL11	-0.7	0.61	-10000	0	-1.3	228	228
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.29	0.34	-10000	0	-0.87	91	91
IL2RG	-0.037	0.22	-10000	0	-0.86	34	34
IL10	-0.5	0.5	-10000	0	-1.2	116	116
IRS1	0.01	0.067	-10000	0	-0.75	4	4
IRS2	0.002	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.2	109	109
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.37	-10000	0	-0.88	108	108
COL1A1	-0.41	0.43	-10000	0	-0.92	198	198
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.48	-10000	0	-1.2	103	103
IL2R gamma/JAK3	-0.16	0.37	-10000	0	-0.83	109	109
TFF3	-0.5	0.5	-10000	0	-1.2	121	121
ALOX15	-0.48	0.48	-10000	0	-1.2	112	112
MYBL1	-0.045	0.22	-10000	0	-0.86	36	36
T-helper 2 cell differentiation	-0.43	0.41	-10000	0	-0.96	129	129
SHC1	0.014	0.039	-10000	0	-0.86	1	1
CEBPB	0	0.14	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.3	-10000	0	-0.78	69	69
mol:PI-3-4-5-P3	-0.28	0.33	-10000	0	-0.84	83	83
PI3K	-0.3	0.36	-10000	0	-0.91	83	83
DOK2	-0.037	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	-0.75	58	58
ITGB3	-0.48	0.49	-10000	0	-1.2	113	113
PIGR	-0.84	0.7	-10000	0	-1.5	267	267
IGHE	0.028	0.09	0.29	12	-0.38	3	15
MAPKKK cascade	-0.2	0.27	-10000	0	-0.73	58	58
BCL6	0.014	0.005	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	111	111
RETNLB	-0.49	0.48	-10000	0	-1.2	106	106
SELP	-0.51	0.52	-10000	0	-1.3	117	117
AICDA	-0.62	0.55	-10000	0	-1.2	189	189

×

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	0.001	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	466	466
EGF/EGFR dimer/SHC	-0.44	0.16	-9999	-0.49	467	467
mol:GDP	-0.36	0.14	-9999	-0.88	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.013	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	-0.33	0.13	-9999	-0.83	10	10
FRAP1	-0.34	0.14	-9999	-0.85	9	9
EGF/EGFR dimer	-0.51	0.18	-9999	-0.57	467	467
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.024	0.12	-9999	-0.66	19	19

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.13	0.27	-10000	0	-0.49	167	167
ACTA1	-0.19	0.36	-10000	0	-0.67	168	168
NUMA1	-0.13	0.27	-10000	0	-0.52	144	144
SPTAN1	-0.19	0.36	-10000	0	-0.67	167	167
LIMK1	-0.19	0.36	-10000	0	-0.67	168	168
BIRC3	-0.12	0.32	-10000	0	-0.86	80	80
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	-0.87	185	185
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.015	0.003	-10000	0	-10000	0	0
PTK2	-0.13	0.27	-10000	0	-0.49	167	167
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.35	-10000	0	-0.65	167	167
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.19	0.36	-10000	0	-0.67	167	167
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.3	0.28	-10000	0	-0.54	283	283
BID	-0.091	0.17	-10000	0	-0.37	104	104
MAP3K1	-0.044	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	-0.19	0.36	-10000	0	-0.67	167	167
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.013	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	-0.64	167	167
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.05	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	104	104
CASP7	0.051	0.13	0.34	80	-10000	0	80
KRT18	-0.002	0.046	-10000	0	-0.3	2	2
apoptosis	-0.18	0.32	-10000	0	-0.69	111	111
DFFA	-0.19	0.36	-10000	0	-0.67	167	167
DFFB	-0.19	0.36	-10000	0	-0.67	167	167
PARP1	-0.013	0.095	0.21	35	-10000	0	35
actin filament polymerization	0.16	0.33	0.72	105	-10000	0	105
TNF	0.003	0.1	-10000	0	-0.8	8	8
CYCS	-0.069	0.13	-10000	0	-0.28	105	105
SATB1	-0.037	0.15	-10000	0	-0.48	3	3
SLK	-0.19	0.36	-10000	0	-0.67	167	167
p15 BID/BAX	-0.074	0.15	-10000	0	-10000	0	0
CASP2	0.031	0.089	-10000	0	-10000	0	0
JNK cascade	0.044	0.11	-10000	0	-10000	0	0
CASP3	-0.21	0.37	-10000	0	-0.71	167	167
LMNB2	0.011	0.085	-10000	0	-0.41	3	3
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.081	0.19	-10000	0	-0.52	80	80
negative regulation of DNA binding	-0.29	0.28	-10000	0	-0.54	283	283
stress fiber formation	-0.18	0.35	-10000	0	-0.65	167	167
GZMB	-0.33	0.51	-10000	0	-0.97	185	185
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.008	0.09	-10000	0	-0.37	7	7
APP	0.01	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	112	112
LMNA	0.011	0.085	-10000	0	-0.39	4	4
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	-0.85	7	7
SREBF1	-0.19	0.36	-10000	0	-0.67	166	166
APAF-1/Caspase 9	-0.009	0.063	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.13	0.26	-10000	0	-0.48	167	167
CFL2	-0.17	0.34	-10000	0	-0.75	105	105
GAS2	-0.2	0.36	-10000	0	-0.66	178	178
positive regulation of apoptosis	0.015	0.085	-10000	0	-0.4	3	3
PRF1	-0.21	0.38	-10000	0	-0.86	131	131

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.25	0.27	-9999	-0.54	244	244
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.064	0.068	-9999	-10000	0	0
AURKB	-0.4	0.44	-9999	-0.86	243	243
AURKC	0.012	0.055	-9999	-0.86	2	2

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.008	0.072	-9999	-0.68	5	5
VEGFR1 homodimer/NRP1	-0.008	0.073	-9999	-0.62	7	7
mol:DAG	-0.26	0.29	-9999	-0.52	287	287
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	234	234
CaM/Ca2+	-0.27	0.25	-9999	-0.92	7	7
HIF1A	0.02	0.058	-9999	-0.72	2	2
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.23	0.21	-9999	-0.95	6	6
PLCG1	-0.27	0.29	-9999	-0.52	287	287
NOS3	-0.18	0.24	-9999	-0.85	6	6
CBL	0.014	0.033	-9999	-0.75	1	1
mol:NO	-0.17	0.24	-9999	-0.8	6	6
FLT1	0.031	0.087	-9999	-0.71	7	7
PGF	-0.47	0.44	-9999	-0.86	286	286
VEGFR1 homodimer/NRP2/VEGFR121	-0.25	0.27	-9999	-0.53	239	239
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-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	287	287
MAPK3	-0.21	0.26	-9999	-0.88	6	6
MAPK1	-0.21	0.26	-9999	-0.88	6	6
PIK3R1	0.014	0.033	-9999	-0.75	1	1
PLGF homodimer	-0.47	0.44	-9999	-0.86	286	286
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	37	37
VEGFA homodimer	-0.38	0.44	-9999	-0.86	233	233
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	234	234
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	-0.91	9	9
VEGFR1 homodimer/PLGF homodimer	-0.32	0.3	-9999	-0.58	287	287
VEGFA	-0.38	0.44	-9999	-0.86	233	233
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.52	287	287
RASA1	0.046	0.079	-9999	-0.65	6	6
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFR1 homodimer	0.031	0.087	-9999	-0.71	7	7
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.014	0.033	-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	235	235
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.99	6	6
PDPK1	-0.22	0.27	-9999	-1	6	6
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-0.53	234	234
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	0.097	-9999	-0.61	12	12

×

Glypican 2 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.05	0.23	-9999	-0.86	39	39
GPC2	-0.085	0.28	-9999	-0.86	59	59
GPC2/Midkine	-0.12	0.28	-9999	-0.74	87	87
neuron projection morphogenesis	-0.12	0.28	-9999	-0.73	87	87

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.027	0.08	-10000	0	-0.73	6	6
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.011	0.064	-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	-0.45	38	38
EPO	-0.4	0.41	-10000	0	-0.9	147	147
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	-0.93	118	118
FLT1	-0.019	0.078	-10000	0	-0.76	5	5
ADORA2A	-0.3	0.34	-10000	0	-0.82	81	81
germ cell development	-0.4	0.44	-10000	0	-0.89	203	203
SLC11A2	-0.29	0.34	-10000	0	-0.81	81	81
BHLHE40	-0.29	0.34	-10000	0	-0.81	81	81
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.52	214	214
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.023	0.057	-10000	0	-1.2	1	1
KDR	-0.015	0.066	-10000	0	-1.4	1	1
PGK1	-0.29	0.34	-10000	0	-0.81	81	81
SIRT1	0.014	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.35	0.42	-10000	0	-1	81	81
EPAS1	-0.27	0.19	-10000	0	-0.44	217	217
SP1	0.026	0.005	-10000	0	-10000	0	0
ABCG2	-0.29	0.35	-10000	0	-0.81	82	82
EFNA1	-0.29	0.35	-10000	0	-0.81	82	82
FXN	-0.3	0.34	-10000	0	-0.82	81	81
POU5F1	-0.43	0.48	-10000	0	-0.95	203	203
neuron apoptosis	0.34	0.4	0.96	81	-10000	0	81
EP300	0.014	0.033	-10000	0	-0.75	1	1
EGLN3	-0.76	0.29	-10000	0	-0.87	456	456
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.004	0.046	-10000	0	-0.53	4	4
VHL	0.014	0.033	-10000	0	-0.75	1	1
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.32	0.37	-10000	0	-0.89	86	86
TWIST1	-0.31	0.35	-10000	0	-0.83	84	84
ELK1	0.026	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.56	82	82
VEGFA	-0.47	0.49	-10000	0	-0.94	240	240
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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
TGFB1	0.007	0.086	-9999	-0.86	5	5
CCL5	-0.36	0.44	-9999	-0.86	221	221
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.22	0.23	-9999	-0.59	91	91
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	91	91
Syndecan-1/Syntenin	-0.2	0.22	-9999	-0.56	91	91
MAPK3	-0.16	0.2	-9999	-0.7	15	15
HGF/MET	-0.033	0.15	-9999	-0.66	26	26
TGFB1/TGF beta receptor Type II	0.007	0.086	-9999	-0.86	5	5
BSG	0.014	0.039	-9999	-0.86	1	1
keratinocyte migration	-0.2	0.21	-9999	-0.55	91	91
Syndecan-1/RANTES	-0.42	0.33	-9999	-0.68	275	275
Syndecan-1/CD147	-0.2	0.19	-9999	-0.57	59	59
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	91	91
LAMA5	0.014	0.033	-9999	-0.75	1	1
positive regulation of cell-cell adhesion	-0.21	0.18	-9999	-0.52	91	91
MMP7	-0.12	0.3	-9999	-0.76	93	93
HGF	-0.021	0.17	-9999	-0.8	23	23
Syndecan-1/CASK	-0.21	0.22	-9999	-0.57	91	91
Syndecan-1/HGF/MET	-0.23	0.22	-9999	-0.63	75	75
regulation of cell adhesion	-0.15	0.2	-9999	-0.67	15	15
HPSE	0.013	0.047	-9999	-0.75	2	2
positive regulation of cell migration	-0.22	0.23	-9999	-0.59	91	91
SDC1	-0.22	0.23	-9999	-0.6	91	91
Syndecan-1/Collagen	-0.22	0.23	-9999	-0.59	91	91
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.086	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	247	247
MAPK1	-0.16	0.2	-9999	-0.7	15	15
homophilic cell adhesion	-0.22	0.22	-9999	-0.58	91	91
MMP1	-0.15	0.34	-9999	-0.83	102	102

×

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	-0.25	0.48	-10000	0	-1.1	68	68
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	0.53	-10000	0	-1.1	88	88
ITGA3	-0.24	0.47	-10000	0	-1.1	62	62
IL17F	-0.15	0.34	-10000	0	-0.74	39	39
IL12B	-0.085	0.29	-10000	0	-0.89	60	60
STAT1 (dimer)	-0.28	0.5	-10000	0	-1.1	82	82
CD4	-0.25	0.48	-10000	0	-1.1	65	65
IL23	-0.28	0.48	-10000	0	-1.2	63	63
IL23R	-0.012	0.15	-10000	0	-0.8	10	10
IL1B	-0.25	0.48	-10000	0	-1.1	66	66
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.25	0.47	-10000	0	-1.1	66	66
TYK2	0.016	0.025	-10000	0	-10000	0	0
STAT4	-0.035	0.2	-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	133	133
IL12RB1	-0.26	0.42	-10000	0	-0.89	159	159
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
IL12Rbeta1/TYK2	-0.2	0.34	-10000	0	-0.7	159	159
IL23R/JAK2	-0.011	0.16	-10000	0	-0.78	9	9
positive regulation of chronic inflammatory response	-0.29	0.53	-10000	0	-1.1	88	88
natural killer cell activation	0.002	0.012	0.063	10	-10000	0	10
JAK2	0.021	0.035	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-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	83	83
CXCL1	-0.29	0.52	-10000	0	-1.2	77	77
T cell proliferation	-0.29	0.53	-10000	0	-1.1	88	88
NFKBIA	0.011	0.009	-10000	0	-10000	0	0
IL17A	-0.1	0.29	-10000	0	-0.59	11	11
PI3K	-0.33	0.4	-10000	0	-1	89	89
IFNG	-0.053	0.07	0.13	4	-0.12	215	219
STAT3 (dimer)	-0.32	0.38	-10000	0	-0.99	84	84
IL18R1	-0.004	0.1	-10000	0	-0.81	8	8
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.38	-10000	0	-0.85	64	64
IL18/IL18R	-0.17	0.28	-10000	0	-0.62	145	145
macrophage activation	-0.017	0.018	-10000	0	-0.045	7	7
TNF	-0.26	0.49	-10000	0	-1.1	68	68
STAT3/STAT4	-0.36	0.43	-10000	0	-1.1	98	98
STAT4 (dimer)	-0.3	0.53	-10000	0	-1.2	91	91
IL18	-0.003	0.1	-10000	0	-0.86	7	7
IL19	-0.25	0.46	-10000	0	-1	75	75
STAT5A (dimer)	-0.28	0.5	-10000	0	-1.1	87	87
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	162	162
MPO	-0.26	0.48	-10000	0	-1.1	70	70
positive regulation of humoral immune response	-0.29	0.53	-10000	0	-1.1	88	88
IL23/IL23R/JAK2/TYK2	-0.3	0.55	-10000	0	-1.2	88	88
IL6	-0.3	0.53	-10000	0	-1.2	90	90
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.016	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	162	162
keratinocyte proliferation	-0.29	0.53	-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	0.064	-9999	-0.82	3	3
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.047	-9999	-0.39	1	1
HIF1A	-0.099	0.039	-9999	-0.42	1	1
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.039	-9999	-0.49	2	2
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.16	-9999	-0.86	499	499
ARNT/IPAS	-0.016	0.096	-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	0.047	-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	0.048	-9999	-0.55	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.047	-9999	-0.39	1	1
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	455	455
HIF1A/RACK1/Elongin B/Elongin C	-0.067	0.05	-9999	-0.54	4	4
VHL	0.014	0.033	-9999	-0.75	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.047	-9999	-0.39	1	1
EGLN3	-0.76	0.29	-9999	-0.86	456	456
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	-0.003	0.035	-9999	-0.61	1	1
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	-0.56	0.11	-9999	-0.57	499	499

×

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	-0.85	277	277
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.31	-9999	-0.84	82	82
SMAD9	-0.064	0.083	-9999	-0.57	10	10
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	452	452
SMAD5/SKI	-0.17	0.16	-9999	-0.5	14	14
SMAD1	0.002	0.042	-9999	-10000	0	0
BMP2	0.01	0.069	-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	355	355
BMPR1A-1B/BAMBI	-0.33	0.23	-9999	-0.85	5	5
AHSG	-0.013	0.13	-9999	-0.86	12	12
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.007	0.058	-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	-0.57	7	7
RGMB	0.012	0.055	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.85	4	4
RGMA	0.008	0.074	-9999	-0.75	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.16	0.13	-9999	-0.56	18	18
BMP2-4/USAG1	-0.31	0.24	-9999	-0.48	335	335
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	14	14
SOSTDC1	-0.48	0.36	-9999	-0.75	334	334
BMP7/BMPR2/BMPR1A-1B	-0.58	0.3	-9999	-0.86	257	257
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.094	-9999	-0.74	8	8
HFE2	-0.018	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	-0.017	0.099	-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	-0.74	350	350
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.024	0.12	-9999	-0.62	20	20
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	-0.02	0.1	-9999	-0.55	19	19
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.18	0.33	-9999	-0.76	128	128
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	355	355
CHRDL1	-0.38	0.38	-9999	-0.75	271	271
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	0.088	-9999	-0.75	7	7
SMURF2	0.014	0.033	-9999	-0.75	1	1
BMP2-4/CHRDL1	-0.26	0.25	-9999	-0.48	273	273
BMP2-4/GREM1	-0.13	0.22	-9999	-0.49	133	133
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.037	0.088	-9999	-0.53	10	10
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.5	0.35	-9999	-0.75	350	350
BMP6	0.004	0.094	-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	-0.001	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	0.058	-9999	-0.75	3	3
FST	-0.074	0.25	-9999	-0.77	59	59
BMP2-4/NOG	-0.095	0.21	-9999	-0.56	88	88
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.55	0.29	-9999	-0.81	257	257

×

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	47	47
SHH Np/Cholesterol/GAS1	-0.037	0.12	-10000	0	-0.45	42	42
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.036	0.12	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	-0.62	33	33
STIL	-0.095	0.17	-10000	0	-0.67	10	10
DHH N/PTCH2	-0.044	0.16	-10000	0	-0.63	36	36
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.62	36	36
PIK3CA	0.014	0.033	-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	322	322
determination of left/right symmetry	-0.13	0.19	-10000	0	-0.62	33	33
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
skeletal system development	-0.44	0.4	-10000	0	-0.73	322	322
IHH N/Hhip	-0.2	0.31	-10000	0	-0.65	160	160
DHH N/Hhip	-0.15	0.26	-10000	0	-0.57	138	138
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.13	0.19	-10000	0	-0.62	33	33
pancreas development	-0.18	0.33	-10000	0	-0.75	129	129
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	-0.032	0.18	-10000	0	-0.75	32	32
somite specification	-0.13	0.19	-10000	0	-0.62	33	33
SHH Np/Cholesterol/PTCH1	-0.14	0.14	-10000	0	-0.67	10	10
SHH Np/Cholesterol/PTCH2	-0.035	0.13	-10000	0	-0.51	36	36
SHH Np/Cholesterol/Megalin	-0.048	0.15	-10000	0	-0.48	51	51
SHH	0.018	0.087	-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	-0.72	7	7
SHH Np/Cholesterol/Hhip	-0.12	0.21	-10000	0	-0.46	135	135
LRP2	-0.051	0.22	-10000	0	-0.75	45	45
receptor-mediated endocytosis	-0.15	0.18	-10000	0	-0.77	19	19
SHH Np/Cholesterol/BOC	-0.009	0.064	-10000	0	-0.45	11	11
SHH Np/Cholesterol/CDO	-0.07	0.18	-10000	0	-0.53	69	69
mesenchymal cell differentiation	0.12	0.21	0.46	135	-10000	0	135
mol:Vitamin D3	-0.11	0.17	-10000	0	-0.67	10	10
IHH N/PTCH2	-0.084	0.22	-10000	0	-0.62	70	70
CDON	-0.084	0.28	-10000	0	-0.86	59	59
IHH N/PTCH1	-0.16	0.2	-10000	0	-0.66	32	32
Megalin/LRPAP1	-0.049	0.16	-10000	0	-0.56	45	45
PTCH2	-0.027	0.19	-10000	0	-0.86	25	25
SHH Np/Cholesterol	-0.01	0.066	-10000	0	-0.46	11	11
PTCH1	-0.16	0.19	-10000	0	-0.66	32	32
HHIP	-0.18	0.33	-10000	0	-0.76	129	129

×

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	-0.7	61	61
AP1	-0.16	0.21	-9999	-0.56	83	83
mol:PIP3	-0.23	0.34	-9999	-0.7	143	143
IKBKB	-0.088	0.17	-9999	-0.34	84	84
AKT1	-0.17	0.21	-9999	-0.73	22	22
IKBKG	-0.088	0.17	-9999	-0.34	82	82
MS4A2	-0.18	0.36	-9999	-0.86	114	114
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.034	-9999	-0.75	1	1
MAP3K1	-0.12	0.26	-9999	-0.58	90	90
mol:Ca2+	-0.16	0.24	-9999	-0.48	143	143
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	0.03	-9999	-0.48	2	2
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.009	0.077	-9999	-0.86	4	4
PLD2	-0.18	0.28	-9999	-0.92	20	20
PTPN13	-0.069	0.16	-9999	-0.5	17	17
PTPN11	0.014	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.044	0.17	-9999	-0.4	9	9
SYK	0.008	0.048	-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	141	141
LAT	-0.25	0.3	-9999	-0.65	155	155
PAK2	-0.15	0.29	-9999	-0.64	114	114
NFATC2	-0.069	0.095	-9999	-0.74	3	3
HRAS	-0.18	0.32	-9999	-0.7	121	121
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	213	213
Antigen/IgE/Fc epsilon R1	-0.24	0.3	-9999	-0.58	213	213
mol:GDP	-0.21	0.36	-9999	-0.77	128	128
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.011	0.034	-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	-0.58	21	21
CHUK	-0.088	0.17	-9999	-0.34	82	82
KLRG1	-0.12	0.15	-9999	-0.55	21	21
VAV1	-0.2	0.32	-9999	-0.69	135	135
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.15	-9999	-0.55	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	94	94
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.17	0.22	-9999	-0.58	85	85
GAB2/PI3K/SHP2	-0.18	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	-0.96	99	99
FCER1G	-0.16	0.34	-9999	-0.87	97	97
FCER1A	-0.022	0.16	-9999	-0.77	22	22
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.28	-9999	-0.55	199	199
MAPK3	0.04	0.026	-9999	-10000	0	0
MAPK1	0.04	0.026	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.75	1	1
MAPK8	-0.012	0.076	-9999	-0.68	1	1
DUSP1	0.014	0.039	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.07	0.074	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.074	0.16	-9999	-0.48	21	21
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.22	0.29	-9999	-0.72	115	115
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	161	161
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.2	0.36	-9999	-0.75	131	131
cytokine secretion	-0.051	0.053	-9999	-10000	0	0
SPHK1	-0.16	0.22	-9999	-0.64	58	58
PTK2	-0.077	0.16	-9999	-0.5	20	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.25	0.31	-9999	-0.77	109	109
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.19	0.31	-9999	-0.68	111	111
MAP2K2	0.034	0.031	-9999	-0.42	1	1
MAP2K1	0.035	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.11	0.15	-9999	-0.53	21	21
MAP2K4	0.017	0.015	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.32	0.41	-9999	-0.73	224	224
mol:Choline	-0.17	0.28	-9999	-0.89	20	20
SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.52	16	16
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.062	0.15	-9999	-0.47	13	13
HCLS1	-0.13	0.18	-9999	-0.67	29	29
PRKCB	-0.14	0.23	-9999	-0.47	124	124
FCGR2B	-0.14	0.34	-9999	-0.86	95	95
IGHE	-0.005	0.01	-9999	-10000	0	0
KLRG1/SHIP	-0.11	0.16	-9999	-0.58	23	23
LCP2	-0.041	0.22	-9999	-0.87	33	33
PLA2G4A	-0.12	0.16	-9999	-0.56	25	25
RASA1	0.014	0.033	-9999	-0.75	1	1
mol:Phosphatidic acid	-0.17	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	0.009	0.086	-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	0.078	0.2	0.63	27	-0.44	3	30
IL27/IL27R/JAK1	-0.083	0.35	0.58	1	-0.86	57	58
TBX21	-0.21	0.41	0.5	1	-0.76	155	156
IL12B	-0.093	0.28	-10000	0	-0.87	60	60
IL12A	0.008	0.032	-10000	0	-0.69	1	1
IL6ST	-0.014	0.14	-10000	0	-0.76	17	17
IL27RA/JAK1	0.01	0.062	-10000	0	-0.7	1	1
IL27	-0.045	0.21	-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	0.078	0.2	0.63	27	-0.44	3	30
T cell proliferation during immune response	0.078	0.2	0.63	27	-0.44	3	30
MAPKKK cascade	-0.078	0.2	0.44	3	-0.63	27	30
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	159	159
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	95	96
IL27/IL27R/JAK2/TYK2	-0.08	0.2	0.44	3	-0.64	27	30
positive regulation of T cell mediated cytotoxicity	-0.078	0.2	0.44	3	-0.63	27	30
STAT1 (dimer)	-0.07	0.51	0.54	118	-1	68	186
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.082	0.18	0.39	3	-0.63	22	25
T cell proliferation	-0.12	0.25	-10000	0	-0.71	48	48
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	0.078	0.2	0.63	27	-0.44	3	30
IFNG	-0.041	0.066	0.13	3	-0.11	235	238
T cell differentiation	-0.011	0.011	0.03	3	-0.026	139	142
STAT3 (dimer)	-0.082	0.18	0.39	3	-0.63	22	25
STAT5A (dimer)	-0.082	0.18	0.39	3	-0.62	23	26
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.77	42	44
STAT4	-0.035	0.2	-10000	0	-0.86	30	30
T cell activation	-0.012	0.007	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.043	0.1	-10000	0	-0.71	1	1
GATA3	-0.61	0.68	-10000	0	-1.3	251	251
IL18	0.005	0.08	-10000	0	-0.68	7	7
positive regulation of mast cell cytokine production	-0.082	0.18	0.38	3	-0.62	22	25
IL27/EBI3	-0.12	0.33	-10000	0	-0.83	85	85
IL27RA	-0.003	0.063	-10000	0	-0.76	1	1
IL6	-0.087	0.28	-10000	0	-0.82	65	65
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0	0.088	-10000	0	-0.6	10	10
IL1B	0.006	0.073	-10000	0	-0.66	6	6
EBI3	-0.12	0.31	-10000	0	-0.88	75	75
TNF	0.004	0.079	-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	-0.67	16	16
STXBP1	0.014	0.033	-9999	-0.75	1	1
ACh/CHRNA1	-0.27	0.31	-9999	-0.63	226	226
RAB3GAP2/RIMS1/UNC13B	-0.018	0.1	-9999	-0.58	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	-0.015	0.15	-9999	-0.86	16	16
mol:ACh	-0.009	0.053	-9999	-0.13	80	80
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	-0.27	0.31	-9999	-0.63	226	226
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.37	0.44	-9999	-0.86	226	226
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.083	0.2	-9999	-0.53	84	84
SNAP25	-0.039	0.12	-9999	-0.33	76	76
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.11	0.28	-9999	-0.75	84	84
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	0.36	-10000	0	-1.1	69	69
NFATC2	-0.079	0.23	-10000	0	-0.68	29	29
NFATC3	-0.021	0.064	-10000	0	-10000	0	0
CD40LG	-0.24	0.44	-10000	0	-1.2	56	56
ITCH	0.054	0.058	-10000	0	-10000	0	0
CBLB	0.054	0.058	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.55	0.56	-10000	0	-1.2	197	197
JUNB	0.013	0.047	-10000	0	-0.75	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.058	-10000	0	-10000	0	0
T cell anergy	0.023	0.095	-10000	0	-0.53	2	2
TLE4	-0.03	0.17	-10000	0	-0.7	7	7
Jun/NFAT1-c-4/p21SNFT	-0.24	0.28	-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	-0.88	91	91
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.72	110	110
AP-1/NFAT1	-0.093	0.16	-10000	0	-0.68	12	12
CALM1	0.028	0.036	-10000	0	-10000	0	0
EGR2	-0.11	0.29	-10000	0	-1.4	9	9
EGR3	-0.11	0.29	-10000	0	-1.4	8	8
NFAT1/FOXP3	-0.28	0.4	-10000	0	-0.94	116	116
EGR1	0.001	0.11	-10000	0	-0.74	11	11
JUN	0.005	0.022	-10000	0	-10000	0	0
EGR4	0.006	0.077	-10000	0	-0.86	4	4
mol:Ca2+	0.009	0.04	-10000	0	-10000	0	0
GBP3	-0.034	0.18	-10000	0	-0.79	9	9
FOSL1	-0.027	0.19	-10000	0	-0.86	25	25
NFAT1-c-4/MAF/IRF4	-0.27	0.36	-10000	0	-0.94	84	84
DGKA	-0.034	0.19	-10000	0	-1	7	7
CREM	0.015	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.21	-10000	0	-1.1	7	7
CTLA4	-0.44	0.58	-10000	0	-1	237	237
NFAT1-c-4 (dimer)/EGR1	-0.17	0.24	-10000	0	-1.1	11	11
NFAT1-c-4 (dimer)/EGR4	-0.17	0.23	-10000	0	-1.2	7	7
FOS	-0.014	0.12	-10000	0	-0.76	13	13
IFNG	-0.5	0.52	-10000	0	-1	232	232
T cell activation	-0.049	0.22	-10000	0	-0.83	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	0.064	0.2	0.91	3	-10000	0	3
TNF	-0.095	0.28	-10000	0	-1.1	13	13
FASLG	-0.34	0.48	-10000	0	-1.2	19	19
TBX21	-0.31	0.44	-10000	0	-0.93	169	169
BATF3	-0.061	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	-0.7	7	7
NFAT1-c-4/ICER1	-0.17	0.21	-10000	0	-1.2	6	6
GATA3	-0.35	0.38	-10000	0	-0.75	251	251
T-helper 1 cell differentiation	-0.49	0.5	-10000	0	-1	233	233
IL2RA	-0.39	0.46	-10000	0	-1.1	128	128
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.03	0.17	-10000	0	-0.72	6	6
E2F1	-0.081	0.28	-10000	0	-0.85	62	62
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.03	0.17	-10000	0	-0.7	7	7
IRF4	-0.18	0.37	-10000	0	-0.86	118	118
PTGS2	-0.21	0.4	-10000	0	-1.1	35	35
CSF2	-0.21	0.4	-10000	0	-1.1	33	33
JunB/Fra1/NFAT1-c-4	-0.18	0.22	-10000	0	-1	10	10
IL4	-0.36	0.29	-10000	0	-0.76	108	108
IL5	-0.2	0.37	-10000	0	-1.1	25	25
IL2	-0.05	0.22	-10000	0	-0.85	16	16
IL3	-0.05	0.049	-10000	0	-10000	0	0
RNF128	0.033	0.16	-10000	0	-0.79	19	19
NFATC1	-0.064	0.2	-10000	0	-0.91	3	3
CDK4	0.035	0.18	0.57	1	-10000	0	1
PTPRK	-0.03	0.17	-10000	0	-0.7	7	7
IL8	-0.22	0.42	-10000	0	-1.1	41	41
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.056	0.17	-9999	-0.53	55	55
EFNA5	-0.057	0.22	-9999	-0.75	49	49
FYN	-0.026	0.16	-9999	-0.48	55	55
neuron projection morphogenesis	-0.056	0.17	-9999	-0.53	55	55
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.056	0.17	-9999	-0.53	55	55
EPHA5	-0.008	0.11	-9999	-0.86	8	8

×

Arf6 signaling events

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
CENTA1/KIF3B	-0.004	0.043	-9999	-0.49	4	4
ARNO/beta Arrestin1-2	-0.018	0.063	-9999	-10000	0	0
EGFR	0	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.75	1	1
USP6	0.014	0.039	-9999	-0.86	1	1
IQSEC1	0.016	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.51	0.18	-9999	-0.57	467	467
ARRB2	-0.014	0.11	-9999	-0.39	38	38
mol:GTP	-0.011	0.048	-9999	-0.29	1	1
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.085	0.28	-9999	-0.86	59	59
EGF	-0.67	0.23	-9999	-0.75	466	466
somatostatin receptor activity	0	0	-9999	-0.001	11	11
ARAP2	0.013	0.047	-9999	-0.75	2	2
mol:GDP	-0.057	0.095	-9999	-0.34	22	22
mol:PI-3-4-5-P3	0	0	-9999	-0.001	4	4
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	0.067	-9999	-0.75	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.033	0.15	-9999	-0.66	26	26
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.087	0.09	-9999	-0.35	16	16
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.44	0.16	-9999	-0.48	467	467
ADRB2	0.013	0.047	-9999	-0.75	2	2
receptor agonist activity	0	0	-9999	0	11	11
actin filament binding	0	0	-9999	-0.001	11	11
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.01	0.067	-9999	-0.75	4	4
GNAQ	0.015	0.001	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	10	10
ARF6/GDP	-0.068	0.14	-9999	-0.4	6	6
ARF6/GDP/GULP/ACAP1	-0.23	0.26	-9999	-0.53	198	198
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.021	0.1	-9999	-0.52	17	17
ACAP1	-0.32	0.43	-9999	-0.86	196	196
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.043	0.15	-9999	-0.59	38	38
EFNA1	0.014	0.039	-9999	-0.86	1	1
HGF	-0.021	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	0.033	-9999	-0.75	1	1
fibronectin binding	0	0	-9999	-0.001	10	10
endosomal lumen acidification	0	0	-9999	-0.001	17	17
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	-10000	0	0
MET	0.007	0.086	-9999	-0.86	5	5
GNA14	0.005	0.088	-9999	-0.75	7	7
GNA15	-0.01	0.15	-9999	-0.86	15	15
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	10	10
GNA11	0.011	0.058	-9999	-0.75	3	3
LHCGR	-0.057	0.22	-9999	-0.86	37	37
AGTR1	-0.027	0.18	-9999	-0.75	29	29
desensitization of G-protein coupled receptor protein signaling pathway	-0.043	0.15	-9999	-0.59	38	38
IPCEF1/ARNO	-0.34	0.13	-9999	-0.82	8	8
alphaIIb/beta3 Integrin	-0.027	0.13	-9999	-0.64	22	22

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.001	0.025	-9999	-0.56	1	1
Necdin/E2F1	-0.083	0.22	-9999	-0.68	63	63
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.081	0.2	-9999	-0.54	76	76
NGF (dimer)/p75(NTR)/BEX1	-0.27	0.31	-9999	-0.56	249	249
NT-4/5 (dimer)/p75(NTR)	-0.054	0.18	-9999	-0.67	42	42
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.034	0.22	-9999	-0.95	9	9
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.1	0.3	-9999	-0.86	69	69
MGDIs/NGR/p75(NTR)/LINGO1	-0.072	0.2	-9999	-0.61	61	61
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.12	0.25	-9999	-0.61	99	99
LINGO1	-0.022	0.18	-9999	-0.86	22	22
Sortilin/TRAF6/NRIF	-0.001	0.014	-9999	-10000	0	0
proBDNF (dimer)	-0.1	0.3	-9999	-0.86	69	69
NTRK1	-0.045	0.21	-9999	-0.76	40	40
RTN4R	0.004	0.1	-9999	-0.85	7	7
neuron apoptosis	-0.067	0.23	-9999	-0.67	30	30
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.062	0.24	-9999	-0.63	78	78
ARHGDIA	0.014	0.033	-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	-0.086	0.21	-9999	-0.58	76	76
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.089	0.22	-9999	-0.58	77	77
Mammalian IAPs/DIABLO	-0.081	0.19	-9999	-0.52	80	80
proNGF (dimer)	-0.067	0.26	-9999	-0.86	49	49
MAGED1	0.014	0.039	-9999	-0.86	1	1
APP	0.014	0.033	-9999	-0.75	1	1
NT-4/5 (dimer)	-0.004	0.093	-9999	-0.86	6	6
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.081	0.2	-9999	-0.54	76	76
NGF	-0.067	0.26	-9999	-0.86	49	49
cell cycle arrest	-0.014	0.25	-9999	-0.56	76	76
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.046	0.11	-9999	-0.57	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.047	0.16	-9999	-0.58	42	42
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.093	0.23	-9999	-0.62	77	77
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.046	0.22	-9999	-0.57	76	76
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.035	0.087	-9999	-0.44	8	8
p75(NTR)/beta APP	-0.047	0.17	-9999	-0.66	37	37
BEX1	-0.27	0.37	-9999	-0.75	191	191
mol:GDP	-0.074	0.24	-9999	-0.64	77	77
NGF (dimer)	-0.35	0.3	-9999	-0.84	88	88
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.066	0.19	-9999	-0.56	61	61
PIK3R1	0.014	0.033	-9999	-0.75	1	1
RAC1/GTP	-0.082	0.21	-9999	-0.56	77	77
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.093	0.23	-9999	-0.63	77	77
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.08	0.22	-9999	-0.67	62	62
NT3 (dimer)	0.005	0.092	-9999	-0.78	7	7
TP53	-0.042	0.22	-9999	-0.91	7	7
PRDM4	-0.047	0.23	-9999	-0.57	76	76
BDNF (dimer)	-0.42	0.36	-9999	-0.86	144	144
PIK3CA	0.014	0.033	-9999	-0.75	1	1
SORT1	0.014	0.033	-9999	-0.75	1	1
activation of caspase activity	-0.079	0.2	-9999	-0.53	76	76
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.086	0.21	-9999	-0.58	76	76
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.025	0.21	-9999	-0.64	22	22
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.047	0.23	-9999	-0.57	76	76
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.094	0.23	-9999	-0.63	78	78
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.054	0.18	-9999	-0.67	42	42
MAPK8	-0.023	0.2	-9999	-0.63	21	21
MAPK9	-0.022	0.2	-9999	-0.64	20	20
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.005	0.092	-9999	-0.78	7	7
NTF4	-0.004	0.093	-9999	-0.86	6	6
NDN	0.011	0.058	-9999	-0.75	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.073	0.18	-9999	-0.91	8	8
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.019	-9999	-10000	0	0
RhoA-B-C/GTP	-0.092	0.23	-9999	-0.62	77	77
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.099	0.21	-9999	-0.52	97	97
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.11	0.23	-9999	-0.56	97	97
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.088	0.22	-9999	-0.66	69	69
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	80	80
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	0.006	0.24	-9999	-0.53	60	60
BAD	-0.011	0.2	-9999	-0.6	21	21
RIPK2	0.014	0.039	-9999	-0.86	1	1
NGFR	-0.045	0.22	-9999	-0.86	36	36
CYCS	-0.036	0.22	-9999	-0.97	9	9
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.086	0.21	-9999	-0.58	77	77
BCL2L11	-0.011	0.2	-9999	-0.6	21	21
BDNF (dimer)/p75(NTR)	-0.13	0.28	-9999	-0.7	99	99
PI3K	-0.087	0.22	-9999	-0.58	76	76
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.086	0.21	-9999	-0.58	76	76
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)	-0.11	0.26	-9999	-0.72	77	77
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.087	0.21	-9999	-0.58	77	77
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.058	-9999	-0.75	3	3
PLG	-0.38	0.38	-9999	-0.75	269	269
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.13	0.23	-9999	-0.67	44	44
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.005	0.18	-9999	-0.53	21	21
E2F1	-0.09	0.29	-9999	-0.86	62	62
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.071	0.15	-9999	-0.6	11	11
NGF (dimer)/TRKA	-0.11	0.24	-9999	-0.63	87	87
MMP7	-0.12	0.3	-9999	-0.76	93	93
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.081	0.2	-9999	-0.54	76	76
MMP3	-0.071	0.25	-9999	-0.86	47	47
APAF-1/Caspase 9	-0.11	0.18	-9999	-0.69	11	11

×

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	-0.014	0.047	-9999	-10000	0	0
NFATC2	-0.017	0.064	-9999	-0.59	3	3
NFATC3	-0.014	0.047	-9999	-10000	0	0
CD40LG	-0.31	0.42	-9999	-0.93	102	102
PTGS2	-0.29	0.39	-9999	-0.86	96	96
JUNB	0.013	0.047	-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	-0.027	0.19	-9999	-0.86	25	25
CREM	0.016	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.73	36	36
FOS	-0.014	0.12	-9999	-0.76	13	13
IFNG	-0.44	0.52	-9999	-0.98	224	224
AP-1/NFAT1-c-4	-0.41	0.41	-9999	-1.1	94	94
FASLG	-0.46	0.52	-9999	-0.98	227	227
NFAT1-c-4/ICER1	-0.081	0.081	-9999	-0.58	3	3
IL2RA	-0.34	0.44	-9999	-1	105	105
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.29	0.38	-9999	-0.87	92	92
JunB/Fra1/NFAT1-c-4	-0.094	0.12	-9999	-0.63	8	8
IL4	-0.28	0.37	-9999	-0.83	90	90
IL2	-0.012	0.11	-9999	-0.77	10	10
IL3	-0.028	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.061	0.25	-9999	-0.86	45	45
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.046	0.14	-9999	-0.72	1	1
CCNA2	-0.16	0.35	-9999	-0.86	101	101
PIK3CA	0.015	0.033	-9999	-0.75	1	1
JAK3	-0.16	0.35	-9999	-0.86	105	105
PIK3R1	0.015	0.033	-9999	-0.74	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	59	59
SHC1	0.015	0.039	-9999	-0.86	1	1
SP1	0.025	0.022	-9999	-10000	0	0
IL2RA	-0.12	0.33	-9999	-0.77	105	105
IL2RB	-0.44	0.44	-9999	-0.86	272	272
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.041	0.22	-9999	-0.86	34	34
G1/S transition of mitotic cell cycle	-0.046	0.2	-9999	-0.53	17	17
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.051	-9999	-0.78	2	2
LCK	-0.02	0.18	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.006	0.12	-9999	-0.86	10	10
CDK6	0.014	0.033	-9999	-0.75	1	1
CCND3	-0.078	0.21	-9999	-0.66	28	28

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.054	0.17	-10000	0	-0.42	38	38
IKBKB	-0.023	0.1	-10000	0	-0.28	2	2
AKT1	-0.023	0.13	-10000	0	-0.31	9	9
IKBKG	-0.023	0.11	-10000	0	-0.3	2	2
CALM1	-0.042	0.1	-10000	0	-0.46	4	4
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
MAP3K1	-0.11	0.25	-10000	0	-0.63	71	71
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.11	0.27	1	-0.5	4	5
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.011	0.09	-10000	0	-10000	0	0
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.033	-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	127	127
CD22	-0.15	0.23	-10000	0	-0.68	51	51
CAMK2G	-0.029	0.098	-10000	0	-0.5	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.009	0.077	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.1	0.19	-10000	0	-0.85	4	4
GO:0007205	-0.055	0.11	0.27	1	-0.51	4	5
SYK	0.013	0.047	-10000	0	-0.75	2	2
ELK1	-0.043	0.1	-10000	0	-0.51	3	3
NFATC1	-0.071	0.2	-10000	0	-0.5	66	66
B-cell antigen/BCR complex	-0.17	0.3	-10000	0	-0.68	127	127
PAG1/CSK	-0.003	0.041	-10000	0	-0.67	2	2
NFKBIB	0.005	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	-0.62	175	175
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	-0.079	0.22	-10000	0	-0.57	64	64
PIK3R1	0.014	0.033	-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	-0.04	0.11	-10000	0	-0.48	6	6
CHUK	-0.023	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	84	84
PTPN6	-0.14	0.21	-10000	0	-0.68	39	39
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.011	0.068	-10000	0	-0.14	105	105
VAV2	-0.17	0.28	-10000	0	-0.8	74	74
ubiquitin-dependent protein catabolic process	0.011	0.037	-10000	0	-0.12	1	1
BTK	-0.088	0.17	0.46	1	-0.42	106	107
CD19	-0.19	0.33	-10000	0	-0.82	91	91
MAP4K1	-0.34	0.43	-10000	0	-0.86	211	211
CD72	-0.19	0.37	-10000	0	-0.86	122	122
PAG1	0.012	0.055	-10000	0	-0.86	2	2
MAPK14	-0.084	0.21	-10000	0	-0.52	67	67
SH3BP5	0.014	0.033	-10000	0	-0.75	1	1
PIK3AP1	-0.037	0.11	-10000	0	-0.55	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.11	0.23	-10000	0	-0.58	77	77
RAF1	-0.025	0.11	-10000	0	-0.54	2	2
RasGAP/p62DOK/SHIP	-0.2	0.32	-10000	0	-0.97	48	48
CD79A	-0.2	0.38	-10000	0	-0.86	127	127
re-entry into mitotic cell cycle	-0.012	0.09	-10000	0	-10000	0	0
RASA1	0.014	0.033	-10000	0	-0.75	1	1
MAPK3	-0.001	0.1	-10000	0	-10000	0	0
MAPK1	-0.001	0.1	-10000	0	-10000	0	0
CD72/SHP1	-0.23	0.33	-10000	0	-0.83	99	99
NFKB1	0.014	0.033	-10000	0	-0.75	1	1
MAPK8	-0.085	0.22	-10000	0	-0.52	68	68
actin cytoskeleton organization	-0.096	0.26	-10000	0	-0.65	73	73
NF-kappa-B/RelA	0.035	0.059	-10000	0	-10000	0	0
Calcineurin	-0.042	0.07	-10000	0	-0.44	2	2
PI3K	-0.14	0.22	-10000	0	-0.6	69	69
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	133	133
DAPP1	-0.11	0.18	-10000	0	-0.61	36	36
cytokine secretion	-0.064	0.19	-10000	0	-0.46	66	66
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	-0.013	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.24	0.37	-10000	0	-0.72	175	175
mol:PI-3-4-5-P3	-0.097	0.15	-10000	0	-0.4	65	65
ETS1	-0.017	0.092	-10000	0	-0.44	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.22	-10000	0	-0.5	126	126
B-cell antigen/BCR complex/LYN	-0.14	0.22	-10000	0	-0.57	71	71
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	-0.71	73	73
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.25	-10000	0	-0.67	64	64
CARD11	-0.15	0.26	-10000	0	-0.62	110	110
FCGR2B	-0.14	0.34	-10000	0	-0.86	95	95
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.005	0.048	-10000	0	-10000	0	0
PTPRC	-0.079	0.27	-10000	0	-0.86	56	56
PDPK1	-0.061	0.1	-10000	0	-0.31	9	9
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	66	66

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.026	0.023	-9999	-0.49	1	1
ADCY5	0.006	0.1	-9999	-0.49	22	22
ADCY6	0.026	0.042	-9999	-0.93	1	1
ADCY7	0.009	0.11	-9999	-0.58	16	16
ADCY1	0.014	0.083	-9999	-0.5	13	13
ADCY2	-0.13	0.27	-9999	-0.58	135	135
ADCY3	0.026	0.023	-9999	-0.49	1	1
ADCY8	-0.16	0.28	-9999	-0.59	160	160
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	-0.51	51	51

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.12	0.24	-10000	0	-0.78	35	35
UGCG	-0.023	0.047	-10000	0	-0.84	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.081	0.19	-10000	0	-0.5	47	47
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	-0.53	45	45
FRAP1	-0.085	0.23	-10000	0	-0.62	49	49
FOXO3	-0.075	0.22	-10000	0	-0.65	35	35
AKT1	-0.093	0.24	-10000	0	-0.64	52	52
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	0.027	0.032	-10000	0	-0.48	2	2
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.022	0.099	-10000	0	-0.58	1	1
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
RPS6KB1	-0.028	0.087	-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	0.35	-10000	0	-0.86	105	105
PIK3R1	0.017	0.034	-10000	0	-0.74	1	1
JAK1	0.019	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-10000	0	-0.75	1	1
MYC	-0.076	0.22	-10000	0	-0.63	43	43
MYB	-0.19	0.34	-10000	0	-0.74	139	139
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.12	0.26	-10000	0	-0.68	62	62
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.035	0.067	-10000	0	-0.47	2	2
mol:PI-3-4-5-P3	-0.12	0.25	-10000	0	-0.66	62	62
Rac1/GDP	0.012	0.033	-10000	0	-0.43	2	2
T cell proliferation	-0.097	0.24	-10000	0	-0.65	47	47
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	-0.008	0.026	-10000	0	-0.05	139	139
PRKCZ	-0.1	0.25	-10000	0	-0.69	47	47
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.58	30	30
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.15	0.26	-10000	0	-0.58	102	102
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	104	104
IL2RB	-0.44	0.44	-10000	0	-0.86	272	272
TERT	-0.11	0.3	-10000	0	-0.86	73	73
E2F1	-0.1	0.2	-10000	0	-0.38	165	165
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	-0.039	0.22	-10000	0	-0.86	34	34
actin cytoskeleton organization	-0.097	0.24	-10000	0	-0.65	47	47
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	-0.018	0.18	-10000	0	-0.85	22	22
BCL2	-0.052	0.18	-10000	0	-0.53	24	24

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.013	0.036	-9999	-0.78	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.023	-9999	-10000	0	0
JMJD2C	-0.001	0.021	-9999	-0.11	18	18
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	0.015	0.045	-9999	-0.86	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.009	0.069	-9999	-0.77	4	4
GSN	0.015	0.008	-9999	-10000	0	0
NCOA2	0.002	0.1	-9999	-0.75	9	9
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.027	-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	0.036	-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	-0.092	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	0.055	-9999	-0.14	449	449
CDK6	0.014	0.033	-9999	-0.74	1	1
TGFB1I1	0.013	0.039	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.15	-9999	-0.6	44	44
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	0.018	-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	499	499
SRF	0.026	0.012	-9999	-10000	0	0
NKX3-1	-0.19	0.069	-9999	-10000	0	0
KLK3	0.023	0.15	-9999	-0.71	21	21
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.013	-9999	-10000	0	0
AOF2	-0.002	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	-0.068	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	-0.068	0.099	-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	0.099	-9999	-0.5	24	24
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.005	0.12	-9999	-0.75	14	14
KLK2	-0.084	0.14	-9999	-0.8	18	18
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.067	0.12	-9999	-0.56	27	27
TMPRSS2	-0.92	0.35	-9999	-1.1	449	449
CCND1	-0.019	0.17	-9999	-0.86	20	20
PIAS1	0.014	0.013	-9999	-10000	0	0
mol:T-DHT	-0.062	0.027	-9999	-0.072	446	446
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	-0.008	0.13	-9999	-0.75	16	16
ZMIZ1	-0.032	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

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0	0.057	0.29	18	-10000	0	18
BUB1B	-0.023	0.12	-10000	0	-0.51	26	26
PLK1	-0.012	0.059	-10000	0	-0.2	10	10
PLK1S1	0.001	0.031	-10000	0	-10000	0	0
KIF2A	-0.003	0.073	-10000	0	-0.56	4	4
regulation of mitotic centrosome separation	-0.012	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	-0.72	126	126
WEE1	-0.001	0.056	-10000	0	-0.3	5	5
cytokinesis	-0.2	0.27	-10000	0	-0.5	234	234
PP2A-alpha B56	-0.14	0.16	-10000	0	-10000	0	0
AURKA	-0.002	0.045	-10000	0	-0.3	6	6
PICH/PLK1	-0.045	0.16	-10000	0	-0.84	18	18
CENPE	-0.063	0.21	-10000	0	-0.63	60	60
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.003	0.072	-10000	0	-0.55	4	4
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.033	-10000	0	-0.75	1	1
TPX2	-0.05	0.12	-10000	0	-0.25	125	125
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.076	0.27	-10000	0	-0.86	54	54
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.025	0.096	-10000	0	-0.28	59	59
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	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	-0.012	0.059	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.16	0.19	-10000	0	-0.46	7	7
TPT1	0.001	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	238	238
CDC25B	0.007	0.088	-10000	0	-0.88	5	5
SGOL1	0	0.057	-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	-0.056	0.24	-10000	0	-0.86	42	42
PLK1/PBIP1	-0.041	0.11	-10000	0	-0.59	18	18
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.003	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	109	109
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	-0.57	234	234
GRASP65/GM130/RAB1/GTP/PLK1	-0.013	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	0.007	0.038	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	120	120
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	234	234
Golgi organization	-0.012	0.059	-10000	0	-0.2	10	10
Cohesin/SA2	-0.024	0.045	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.38	0.44	-10000	0	-0.86	234	234
APC/C/CDC20	-0.045	0.18	-10000	0	-0.64	42	42
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.04	0.11	-10000	0	-0.58	18	18
PRC1	0.006	0.094	-10000	0	-0.86	6	6
ECT2	0.001	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	-0.023	0.12	-10000	0	-0.5	26	26
spindle assembly	-0.006	0.048	-10000	0	-0.18	6	6
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	234	234
CCNB1	0.002	0.11	-10000	0	-0.88	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.005	0.053	-10000	0	-0.46	3	3
TUBG1	0.001	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.026	0.098	-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

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.25	0.41	-10000	0	-0.82	172	172
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	-0.85	7	7
GR alpha/HSP90/FKBP51/HSP90	0.055	0.13	0.39	5	-0.59	7	12
PRL	-0.014	0.11	-10000	0	-0.56	1	1
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.56	87	-0.62	2	89
RELA	0.004	0.076	-10000	0	-10000	0	0
FGG	-0.15	0.43	0.57	13	-0.73	149	162
GR beta/TIF2	0.052	0.14	0.42	6	-0.55	7	13
IFNG	-0.41	0.44	-10000	0	-0.86	219	219
apoptosis	-0.093	0.21	0.43	1	-0.62	10	11
CREB1	-0.015	0.1	-10000	0	-0.39	6	6
histone acetylation	0.018	0.13	0.39	10	-0.42	8	18
BGLAP	-0.008	0.13	-10000	0	-0.74	3	3
GR/PKAc	0.065	0.1	0.37	4	-0.6	1	5
NF kappa B1 p50/RelA	0.01	0.15	-10000	0	-0.58	7	7
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.047	0.093	0.3	15	-10000	0	15
GATA3	-0.35	0.38	-10000	0	-0.74	251	251
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.027	0.16	-10000	0	-0.68	17	17
GSK3B	0.011	0.007	-10000	0	-10000	0	0
NR1I3	-0.057	0.22	-10000	0	-0.83	12	12
CSN2	0.044	0.19	0.46	8	-0.66	1	9
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	62	62
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.005	0.21	0.38	2	-0.58	25	27
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.058	0.22	-10000	0	-0.84	12	12
JUN	-0.22	0.25	-10000	0	-0.64	74	74
IL4	-0.023	0.12	-10000	0	-0.58	2	2
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	0.31	2	-0.68	85	87
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.061	0.12	0.41	2	-0.6	4	6
cortisol/GR alpha (monomer)	0.15	0.34	0.65	100	-0.81	1	101
NCOA2	0.003	0.1	-10000	0	-0.75	9	9
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	-0.82	107	107
AFP	-0.35	0.56	-10000	0	-1.4	109	109
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.084	0.15	0.51	8	-0.62	1	9
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	-1.1	70	70
KRT14	-0.15	0.3	-10000	0	-0.83	75	75
TBP	0.028	0.01	-10000	0	-10000	0	0
CREBBP	0.047	0.081	-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	-0.33	0.34	-10000	0	-0.82	108	108
MAPK14	0.012	0.007	-10000	0	-10000	0	0
MAPK10	0.004	0.075	-10000	0	-0.75	5	5
MAPK11	0.009	0.04	-10000	0	-0.88	1	1
KRT5	-0.26	0.39	-10000	0	-0.9	112	112
interleukin-1 receptor activity	0	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.054	-10000	0	-1.2	1	1
CGA	-0.13	0.37	-10000	0	-1.2	51	51
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.089	0.15	0.45	36	-10000	0	36
MAPK3	0.011	0.007	-10000	0	-10000	0	0
MAPK1	0.012	0.007	-10000	0	-10000	0	0
ICAM1	-0.049	0.23	-10000	0	-0.81	24	24
NFKB1	0.003	0.086	-10000	0	-0.9	1	1
MAPK8	-0.14	0.2	-10000	0	-0.51	49	49
MAPK9	0.012	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.098	0.22	0.43	1	-0.64	12	13
BAX	0.052	0.028	-10000	0	-10000	0	0
POMC	-0.037	0.17	-10000	0	-0.81	7	7
EP300	0.045	0.085	-10000	0	-0.6	1	1
cortisol/GR alpha (dimer)/p53	0.16	0.29	0.57	99	-0.7	1	100
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.071	0.27	3	-10000	0	3
SGK1	0.1	0.096	-10000	0	-10000	0	0
IL13	-0.36	0.28	-10000	0	-0.76	110	110
IL6	-0.12	0.38	-10000	0	-0.98	72	72
PRKACG	0.003	0.007	-10000	0	-10000	0	0
IL5	-0.29	0.21	-10000	0	-0.7	40	40
IL2	-0.17	0.25	-10000	0	-0.86	26	26
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	-0.078	0.3	-10000	0	-0.9	46	46
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	0.15	0.26	0.54	83	-0.65	1	84
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.15	0.39	43	-10000	0	43
NF kappa B1 p50/RelA/Cbp	0.063	0.14	-10000	0	-0.94	1	1
JUN (dimer)	-0.21	0.25	-10000	0	-0.63	75	75
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.058	0.22	-10000	0	-0.82	24	24
NR3C1	0.08	0.19	0.49	35	-0.95	1	36
NR4A1	0.002	0.13	-10000	0	-0.73	16	16
TIF2/SUV420H1	-0.01	0.073	-10000	0	-0.56	9	9
MAPKKK cascade	-0.093	0.21	0.43	1	-0.62	10	11
cortisol/GR alpha (dimer)/Src-1	0.15	0.28	0.56	97	-0.8	1	98
PBX1	-0.003	0.13	-10000	0	-0.74	15	15
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.097	0.37	-10000	0	-1.2	43	43
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.15	0.4	42	-10000	0	42
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.15	0.26	0.54	83	-0.65	1	84
mol:cortisol	0.063	0.2	0.36	93	-0.26	26	119
MMP1	-0.23	0.39	-10000	0	-0.97	102	102

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	233	233
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.03	0.1	-9999	-0.36	43	43
mol:S1P	-0.024	0.095	-9999	-0.41	6	6
S1P1/S1P/Gi	-0.047	0.14	-9999	-0.51	13	13
GNAO1	0.01	0.084	-9999	-0.84	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.054	0.087	-9999	-0.63	2	2
PLCG1	-0.028	0.13	-9999	-0.51	8	8
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	0.011	0.058	-9999	-0.75	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.25	0.3	-9999	-0.58	233	233
S1P1/S1P	-0.21	0.21	-9999	-0.63	23	23
negative regulation of cAMP metabolic process	-0.046	0.14	-9999	-0.5	13	13
MAPK3	-0.038	0.16	-9999	-0.57	25	25
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	-0.2	0.26	-9999	-0.67	59	59
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.17	-9999	-0.52	22	22
receptor internalization	-0.2	0.2	-9999	-0.57	23	23
PTGS2	-0.048	0.24	-9999	-0.99	26	26
Rac1/GTP	-0.17	0.17	-9999	-0.52	22	22
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	233	233
negative regulation of T cell proliferation	-0.046	0.14	-9999	-0.5	13	13
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.011	0.058	-9999	-0.75	3	3
MAPK1	-0.038	0.16	-9999	-0.57	25	25
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.64	22	22
ABCC1	0.016	0.002	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.3	-9999	-0.76	36	36
CRP	-0.2	0.39	-9999	-0.9	91	91
cell cycle arrest	-0.18	0.35	-9999	-0.78	83	83
TIMP1	-0.15	0.33	-9999	-0.77	70	70
IL6ST	-0.013	0.14	-9999	-0.74	17	17
Rac1/GDP	-0.14	0.26	-9999	-0.59	88	88
AP1	0.021	0.11	-9999	-0.58	2	2
GAB2	0.011	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.37	-9999	-0.85	77	77
HSP90B1	0.004	0.088	-9999	-10000	0	0
GAB1	0.014	0.006	-9999	-10000	0	0
MAPK14	0.017	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	-0.017	0.14	-9999	-0.63	5	5
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.28	-9999	-0.65	69	69
MITF	-0.024	0.14	-9999	-0.6	4	4
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	83	83
STAT1	-0.005	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.31	-9999	-0.75	40	40
PIK3CA	0.017	0.034	-9999	-0.74	1	1
PI3K	-0.002	0.035	-9999	-0.56	2	2
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.018	0.13	-9999	-0.75	2	2
MAPK11	0.016	0.13	-9999	-0.7	4	4
STAT3 (dimer)/FOXO1	-0.071	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	0.44	-9999	-0.88	159	159
PIK3R1	0.016	0.033	-9999	-0.74	1	1
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.32	-9999	-0.77	55	55
FGG	-0.28	0.43	-9999	-0.87	129	129
macrophage differentiation	-0.18	0.35	-9999	-0.78	83	83
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.069	0.17	-9999	-0.54	34	34
JUNB	-0.14	0.3	-9999	-0.76	37	37
FOS	-0.009	0.12	-9999	-0.76	13	13
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.035	0.15	-9999	-0.43	28	28
STAT1/PIAS1	-0.047	0.16	-9999	-0.49	19	19
GRB2/SOS1/GAB family/SHP2/PI3K	0.022	0.038	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.36	-9999	-0.82	83	83
PRKCD	-0.15	0.3	-9999	-0.69	67	67
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.032	0.12	-9999	-0.63	5	5
gp130 (dimer)/JAK1/JAK1/LMO4	-0.003	0.09	-9999	-0.47	17	17
Rac1/GTP	-0.18	0.23	-9999	-0.6	96	96
HCK	-0.032	0.2	-9999	-0.86	28	28
MAPKKK cascade	0.026	0.06	-9999	-10000	0	0
bone resorption	-0.18	0.35	-9999	-0.79	77	77
IRF1	-0.14	0.31	-9999	-0.75	41	41
mol:GDP	-0.15	0.27	-9999	-0.55	133	133
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.27	-9999	-0.56	133	133
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.003	0.12	-9999	-0.64	3	3
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.078	0.21	-9999	-0.63	65	65
gp130 (dimer)/TYK2/TYK2/LMO4	-0.013	0.085	-9999	-0.47	17	17
gp130 (dimer)/JAK2/JAK2/LMO4	-0.013	0.085	-9999	-0.47	17	17
IL6	-0.092	0.28	-9999	-0.82	65	65
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	-0.035	0.13	-9999	-0.42	14	14
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.29	-9999	-0.75	82	82
MCL1	0.075	0.023	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.24	0.28	-9999	-0.86	73	73
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.014	0.089	-9999	-0.57	13	13
IFNAR2	0.015	0.007	-9999	-10000	0	0
AKT1	0.014	0.069	-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	466	466
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	-0.79	73	73
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	242	242
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	-0.72	62	62
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.24	0.29	-9999	-0.89	73	73
CCND1	-0.22	0.27	-9999	-0.79	78	78
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	-0.23	0.3	-9999	-0.55	237	237
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	-0.017	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	-0.005	0.12	-9999	-0.76	13	13
IFN-gamma/IRF1	-0.3	0.32	-9999	-0.65	237	237
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.003	0.13	-9999	-0.86	11	11
Telomerase	-0.019	0.16	-9999	-0.4	45	45
IRF1	0.016	0.039	-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	-0.006	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	63	63
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.009	0.096	-9999	-0.67	10	10
MAPK1	0.009	0.096	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.008	0.086	-9999	-0.86	5	5
NFKB1	0.014	0.033	-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	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.51	0.18	-9999	-0.57	467	467
MYC	-0.018	0.16	-9999	-0.86	19	19
IL2	-0.008	0.12	-9999	-0.87	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	0.008	0.086	-9999	-0.86	5	5
TRF2/BLM	-0.013	0.09	-9999	-0.63	11	11
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.21	0.26	-9999	-0.79	72	72
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	-0.72	61	61
Smad3/Myc	-0.02	0.13	-9999	-0.6	23	23
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.85	237	237
Telomerase/PinX1	-0.18	0.23	-9999	-0.72	61	61
Telomerase/AKT1/mTOR/p70S6K	-0.013	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	-0.72	61	61
response to DNA damage stimulus	0.004	0.006	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.18	0.23	-9999	-0.74	51	51
E2F1	-0.091	0.29	-9999	-0.87	62	62
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.14	0.33	-9999	-0.86	89	89
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

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
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	173	173
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	-0.66	0.37	-9999	-0.86	397	397
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	-0.67	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	183	183
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	172	172
PAFAH/LIS1	-0.44	0.24	-9999	-0.58	397	397
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.098	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	0.033	-9999	-0.75	1	1
PAFAH1B2	0.014	0.033	-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	0.15	-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	-0.094	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	-0.51	17	17
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6
CDC42	0	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	233	233
alphaV beta3 Integrin	-0.008	0.069	-9999	-0.54	8	8
PTK2	-0.15	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	-0.083	0.19	-9999	-0.53	79	79
VEGFA	-0.38	0.44	-9999	-0.86	233	233
ILK	-0.083	0.19	-9999	-0.53	79	79
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.076	0.17	-9999	-0.49	71	71
PTK2B	-0.19	0.27	-9999	-0.88	1	1
alphaV/beta3 Integrin/JAM-A	-0.069	0.15	-9999	-0.81	1	1
CBL	0.014	0.033	-9999	-0.75	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.48	243	243
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.067	-9999	-0.52	6	6
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.14	-9999	-0.47	44	44
alphaV/beta3 Integrin/Syndecan-1	-0.009	0.065	-9999	-0.48	10	10
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-9999	-0.8	4	4
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.75	1	1
alphaV/beta3 Integrin/Osteopontin	-0.007	0.059	-9999	-0.48	8	8
RPS6KB1	-0.043	0.13	-9999	-0.73	4	4
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.042	0.097	-9999	-0.82	3	3
GPR124	0.012	0.055	-9999	-0.86	2	2
MAPK1	-0.042	0.097	-9999	-0.82	3	3
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
alphaV/beta3 Integrin/Tumstatin	-0.057	0.16	-9999	-0.48	61	61
cell adhesion	-0.17	0.18	-9999	-0.83	1	1
ANGPTL3	-0.34	0.38	-9999	-0.75	239	239
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	233	233
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	0.01	0.067	-9999	-0.75	4	4
IGF1	0.006	0.094	-9999	-0.86	6	6
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.006	0.054	-9999	-0.51	6	6
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.004	0.042	-9999	-0.48	4	4
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.017	0.095	-9999	-0.54	16	16
CSF1	0.014	0.033	-9999	-0.75	1	1
PIK3C2A	-0.085	0.2	-9999	-0.54	80	80
PI4 Kinase/Pyk2	-0.23	0.24	-9999	-0.76	45	45
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	233	233
FAK1/Vinculin	-0.11	0.18	-9999	-0.56	3	3
alphaV beta3/Integrin/ppsTEM5	-0.006	0.055	-9999	-0.51	6	6
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.1	0.28	-9999	-0.76	79	79
BCAR1	0.014	0.033	-9999	-0.75	1	1
FGF2	0.008	0.077	-9999	-0.77	5	5
F11R	0.025	0.06	-9999	-0.58	5	5
alphaV/beta3 Integrin/Lactadherin	-0.005	0.049	-9999	-0.5	5	5
alphaV/beta3 Integrin/TGFBR2	-0.004	0.042	-9999	-0.48	4	4
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.002	0.042	-9999	-0.85	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.003	0.038	-9999	-0.44	4	4
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.049	0.23	-9999	-0.86	38	38
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.88	1	1
SDC1	0.007	0.082	-9999	-0.75	6	6
VAV3	0.039	0.084	-9999	-0.8	1	1
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.067	-9999	-0.75	4	4
FAK1/Paxillin	-0.11	0.18	-9999	-0.56	3	3
cell migration	-0.09	0.17	-9999	-0.52	2	2
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.061	0.14	-9999	-1.1	1	1
SPP1	0.01	0.067	-9999	-0.75	4	4
KDR	0.014	0.033	-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	-0.07	0.24	-9999	-0.75	58	58
angiogenesis	0.004	0.15	-9999	-0.8	3	3
Rac1/GTP	-0.012	0.067	-9999	-0.73	1	1
EDIL3	-0.005	0.13	-9999	-0.79	13	13
cell proliferation	-0.004	0.041	-9999	-0.47	4	4

×

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

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
MAP4K1	-0.17	0.27	-10000	0	-0.54	92	92
CRKL	0.017	0.12	-10000	0	-0.57	8	8
HRAS	-0.044	0.18	-10000	0	-0.51	41	41
mol:PIP3	-0.004	0.11	-10000	0	-0.45	21	21
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.014	0.033	-10000	0	-0.75	1	1
GAB1	0.006	0.12	-10000	0	-0.5	21	21
FOXO3	0.024	0.11	-10000	0	-0.51	8	8
AKT1	0.014	0.11	-10000	0	-0.46	21	21
BAD	0.022	0.11	-10000	0	-0.59	6	6
megakaryocyte differentiation	-0.071	0.21	-10000	0	-0.45	111	111
GSK3B	0.024	0.11	-10000	0	-0.48	10	10
RAF1	-0.012	0.15	-10000	0	-0.54	3	3
SHC1	0.014	0.039	-10000	0	-0.86	1	1
STAT3	0.007	0.12	-10000	0	-0.5	21	21
STAT1	-0.016	0.24	-10000	0	-1	21	21
HRAS/SPRED1	-0.068	0.12	-10000	0	-0.43	19	19
cell proliferation	0.006	0.12	-10000	0	-0.5	21	21
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	-0.44	30	30
HRAS/SPRED2	-0.068	0.12	-10000	0	-0.43	20	20
LYN/TEC/p62DOK	-0.018	0.1	-10000	0	-0.66	5	5
MAPK3	0.011	0.12	-10000	0	-0.37	2	2
STAP1	-0.32	0.22	-10000	0	-0.48	198	198
GRAP2	-0.043	0.22	-10000	0	-0.86	35	35
JAK2	-0.067	0.19	-10000	0	-0.91	21	21
STAT1 (dimer)	-0.014	0.23	-10000	0	-1	21	21
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.22	-10000	0	-0.56	48	48
actin filament polymerization	0.001	0.13	-10000	0	-0.48	27	27
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.29	0.23	-10000	0	-0.87	30	30
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
CBL/CRKL/GRB2	-0.014	0.093	-10000	0	-0.59	5	5
PI3K	-0.02	0.11	-10000	0	-0.46	22	22
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.34	-10000	0	-1.3	23	23
MAPK8	0.006	0.13	-10000	0	-0.52	21	21
STAT3 (dimer)	0.007	0.12	-10000	0	-0.49	21	21
positive regulation of transcription	0.014	0.099	-10000	0	-0.31	1	1
mol:GDP	-0.11	0.19	-10000	0	-0.62	44	44
PIK3C2B	0.007	0.12	-10000	0	-0.5	21	21
CBL/CRKL	0.026	0.11	-10000	0	-0.62	5	5
FER	0.005	0.13	-10000	0	-0.5	23	23
SH2B3	0.007	0.12	-10000	0	-0.5	21	21
PDPK1	0.006	0.1	-10000	0	-0.49	9	9
SNAI2	0.006	0.13	-10000	0	-0.5	23	23
positive regulation of cell proliferation	0	0.19	-10000	0	-0.7	28	28
KITLG	0	0.11	-10000	0	-0.77	10	10
cell motility	0	0.19	-10000	0	-0.7	28	28
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.04	0.071	-10000	0	-10000	0	0
STAT5A (dimer)	0.003	0.16	-10000	0	-0.59	29	29
SOCS1	0.006	0.094	-10000	0	-0.86	6	6
cell migration	0.044	0.2	0.51	68	-10000	0	68
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.29	0.42	-10000	0	-0.86	182	182
VAV1	-0.2	0.38	-10000	0	-0.86	124	124
GRB10	0.006	0.12	-10000	0	-0.5	21	21
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.035	0.12	-10000	0	-0.46	33	33
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.005	0.13	-10000	0	-0.42	2	2
CBL	0.014	0.033	-10000	0	-0.75	1	1
KIT	-0.01	0.28	-10000	0	-1.2	28	28
MAP2K2	0.004	0.13	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.019	0.1	-10000	0	-0.66	5	5
STAT5A	0.002	0.17	-10000	0	-0.61	29	29
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.006	0.12	-10000	0	-0.49	23	23
SHC/GRAP2	-0.046	0.17	-10000	0	-0.66	36	36
PTPRO	-0.073	0.22	-10000	0	-0.46	111	111
SH2B2	0.001	0.13	-10000	0	-0.49	27	27
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.045	0.2	-10000	0	-0.52	68	68
CREBBP	0.045	0.012	-10000	0	-10000	0	0
BCL2	0.042	0.069	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.019	0.045	-9999	-10000	0	0
BIRC5	-0.24	0.4	-9999	-0.86	153	153
NFKBIA	0.047	0.04	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.76	104	104
AKT1	0.047	0.04	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.017	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	0.019	0.045	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.011	0.058	-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	0.043	-9999	-0.29	6	6
AURKAIP1	0.011	0.061	-9999	-0.78	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	0.079	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.017	0.04	-9999	-10000	0	0
AURKA	0.027	0.055	-9999	-0.34	6	6
AURKB	-0.14	0.15	-9999	-0.29	243	243
CDC25B	0.018	0.062	-9999	-0.58	2	2
G2/M transition checkpoint	0.015	0.053	-9999	-0.44	3	3
mRNA polyadenylation	-0.074	0.19	-9999	-0.44	104	104
Aurora A/CPEB	-0.074	0.19	-9999	-0.45	104	104
Aurora A/TACC1/TRAP/chTOG	0.021	0.044	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.019	0.045	-9999	-10000	0	0
regulation of centrosome cycle	-0.006	0.065	-9999	-0.73	4	4
spindle assembly	-0.002	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	153	153
CENPA	-0.12	0.14	-9999	-0.3	168	168
Aurora A/PP2A	0.019	0.045	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.053	0.035	-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	0.033	-9999	-0.75	1	1
Ajuba/Aurora A	0.015	0.053	-9999	-0.44	3	3
mitotic prometaphase	0.037	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.049	-9999	-0.34	6	6
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.009	0.077	-9999	-0.86	4	4
Aurora A/Antizyme1	0.017	0.061	-9999	-0.49	3	3
Aurora A/RasGAP	0.018	0.05	-9999	-0.47	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	-0.67	125	125
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.088	0.24	-9999	-0.52	125	125
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.009	0.078	-9999	-0.68	7	7
Metarhodopsin II/Arrestin	-0.018	0.1	-9999	-0.59	16	16
PDE6G/GNAT1/GTP	-0.013	0.084	-9999	-0.56	12	12
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.005	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	21	21
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.037	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.22	-9999	-0.85	21	21
CNGB1	-0.009	0.13	-9999	-0.86	11	11
RDH5	-0.004	0.13	-9999	-0.84	12	12
SAG	0.001	0.038	-9999	-0.86	1	1
mol:Ca2+	-0.068	0.22	-9999	-0.78	21	21
Na + (4 Units)	-0.1	0.2	-9999	-0.75	21	21
RGS9	-0.008	0.14	-9999	-0.82	15	15
GNB1/GNGT1	-0.23	0.32	-9999	-0.67	179	179
GNAT1/GDP	-0.038	0.13	-9999	-0.53	15	15
GUCY2D	-0.03	0.19	-9999	-0.86	25	25
GNGT1	-0.29	0.42	-9999	-0.86	179	179
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	28	28
mol:11-cis-retinal	-0.004	0.13	-9999	-0.83	12	12
mol:cGMP	-0.041	0.14	-9999	-0.53	38	38
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.034	0.15	-9999	-0.66	27	27
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.12	0.3	-9999	-0.75	95	95
Metarhodopsin II	-0.016	0.093	-9999	-0.55	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.043	0.15	-9999	-0.56	38	38
RGS9BP	-0.019	0.16	-9999	-0.75	23	23
Metarhodopsin II/Transducin	-0.12	0.16	-9999	-0.62	11	11
GCAP Family/Ca ++	-0.017	0.1	-9999	-0.56	16	16
PDE6A/B	-0.036	0.15	-9999	-0.66	28	28
mol:Pi	-0.036	0.13	-9999	-0.5	38	38
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.27	-9999	-0.55	181	181
PDE6B	0.007	0.082	-9999	-0.75	6	6
PDE6A	-0.025	0.18	-9999	-0.86	23	23
PDE6G	0.008	0.077	-9999	-0.77	5	5
RHO	-0.015	0.15	-9999	-0.86	15	15
PDE6	-0.057	0.16	-9999	-0.83	8	8
GUCA1A	-0.01	0.12	-9999	-0.86	10	10
GC2/GCAP Family	-0.017	0.099	-9999	-0.56	16	16
GUCA1C	0.001	0.047	-9999	-0.75	2	2
GUCA1B	0.007	0.086	-9999	-0.86	5	5

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	172	172
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.003	0.043	-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	-0.45	184	184
LRPAP1/LRP8	-0.001	0.029	-9999	-0.67	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	0.033	-9999	-0.75	1	1
DAB1/NCK2	-0.14	0.18	-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	-0.84	76	76
CDK5R1	0.016	0.001	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.75	172	172
PIK3R1	0.014	0.033	-9999	-0.75	1	1
RELN/LRP8/Fyn	-0.16	0.23	-9999	-0.48	173	173
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.26	-9999	-0.9	24	24
MAPK8	0.014	0.033	-9999	-0.75	1	1
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.45	183	183
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.51	18	18
RELN/LRP8	-0.16	0.23	-9999	-0.48	173	173
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	0.041	-9999	-0.67	2	2
RAP1A	-0.11	0.17	-9999	-0.76	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.047	-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	-0.029	0.12	-9999	-0.53	3	3
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	0.033	-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	0.083	-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	3	3
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.085	0.31	-10000	0	-0.91	29	29
NCK1/PAK1/Dok-R	-0.083	0.11	-10000	0	-0.42	27	27
NCK1/Dok-R	-0.084	0.27	-10000	0	-1.1	31	31
PIK3CA	0.005	0.034	-10000	0	-0.74	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	0.039	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.32	0.42	-10000	0	-0.85	194	194
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.058	0.23	-10000	0	-0.96	30	30
FN1	-0.049	0.23	-10000	0	-0.86	38	38
PLD2	0.032	0.3	-10000	0	-1.1	30	30
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.025	0.17	-10000	0	-0.75	28	28
ELK1	0.061	0.27	-10000	0	-0.97	30	30
GRB7	0.005	0.088	-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	-0.049	0.23	-10000	0	-0.86	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.084	0.27	-10000	0	-1.1	31	31
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.05	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	0.034	-10000	0	-0.75	1	1
ANGPT2	-0.21	0.38	-10000	0	-0.65	162	162
BMX	-0.037	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	-0.74	24	24
ANGPT4	-0.019	0.15	-10000	0	-0.87	16	16
response to hypoxia	-0.003	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.025	0.32	-10000	0	-1.2	30	30
alpha5/beta1 Integrin	-0.049	0.17	-10000	0	-0.67	38	38
FGF2	0.01	0.079	-10000	0	-0.77	5	5
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	25	25
mol:L-citrulline	-0.05	0.26	-10000	0	-0.65	29	29
AGTR1	-0.038	0.18	-10000	0	-0.75	29	29
MAPK14	-0.004	0.31	-10000	0	-1.2	29	29
Tie2/SHP2	-0.061	0.25	-10000	0	-1.1	28	28
TEK	-0.046	0.29	-10000	0	-1.2	28	28
RPS6KB1	-0.048	0.28	-10000	0	-0.86	29	29
Angiotensin II/AT1	-0.045	0.13	-10000	0	-0.58	29	29
Tie2/Ang1/GRB2	-0.005	0.3	-10000	0	-1.1	30	30
MAPK3	0.045	0.28	-10000	0	-0.99	30	30
MAPK1	0.045	0.28	-10000	0	-0.99	30	30
Tie2/Ang1/GRB7	-0.009	0.31	-10000	0	-1.2	30	30
NFKB1	0.014	0.033	-10000	0	-0.75	1	1
MAPK8	0.032	0.3	-10000	0	-1.1	30	30
PI3K	-0.071	0.32	-10000	0	-1.1	29	29
FES	-0.009	0.31	-10000	0	-1.1	30	30
Crk/Dok-R	-0.083	0.26	-10000	0	-1.1	30	30
Tie2/Ang1/ABIN2	-0.005	0.3	-10000	0	-1.1	30	30
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.074	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	-0.048	0.28	-10000	0	-0.86	29	29
Tie2/Ang2	-0.19	0.4	-10000	0	-1	25	25
Tie2/Ang1	0.024	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	0.028	0.31	-10000	0	-1.1	30	30
mol:Choline	0.035	0.28	-10000	0	-1	30	30
cell migration	-0.055	0.071	-10000	0	-10000	0	0
FYN	-0.15	0.36	-10000	0	-0.86	24	24
DOK2	-0.037	0.21	-10000	0	-0.86	31	31
negative regulation of cell cycle	-0.097	0.3	-10000	0	-0.6	24	24
ETS1	0.028	0.037	-10000	0	-10000	0	0
PXN	-0.026	0.25	-10000	0	-0.7	29	29
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.061	0.28	-10000	0	-0.75	29	29
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.009	0.11	-10000	0	-0.8	8	8
MAPKKK cascade	0.035	0.28	-10000	0	-1	30	30
RASA1	0.014	0.033	-10000	0	-0.75	1	1
Tie2/Ang1/Shc	-0.004	0.3	-10000	0	-1.1	30	30
NCK1	0.014	0.033	-10000	0	-0.75	1	1
vasculogenesis	-0.041	0.24	-10000	0	-0.58	29	29
mol:Phosphatidic acid	0.035	0.28	-10000	0	-1	30	30
mol:Angiotensin II	-0.017	0.022	-10000	0	-10000	0	0
mol:NADP	-0.05	0.26	-10000	0	-0.65	29	29
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	29	29
MMP2	0.027	0.31	-10000	0	-1.1	30	30

×

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	-0.048	0.1	-10000	0	-0.55	5	5
PTP1B/AKT1	-0.031	0.047	-10000	0	-0.39	3	3
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.049	0.053	-10000	0	-0.37	6	6
EGFR	-0.013	0.11	-10000	0	-0.87	9	9
EGF/EGFR	-0.37	0.14	-10000	0	-0.41	466	466
CSF1	0.014	0.033	-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	-0.049	0.087	-10000	0	-0.45	18	18
Insulin Receptor/Insulin	-0.008	0.034	-10000	0	-10000	0	0
HCK	-0.032	0.2	-10000	0	-0.86	28	28
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.035	0.05	-10000	0	-0.42	3	3
EGF	-0.67	0.23	-10000	0	-0.75	466	466
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	40	40
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.033	0.055	-10000	0	-0.45	6	6
cell migration	0.049	0.053	0.37	6	-10000	0	6
STAT3	0.015	0.001	-10000	0	-10000	0	0
PRLR	-0.09	0.26	-10000	0	-0.75	68	68
ITGA2B	-0.022	0.16	-10000	0	-0.86	18	18
CSF1R	0.004	0.1	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.074	0.19	-10000	0	-0.57	68	68
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	-0.03	0.042	-10000	0	-0.42	2	2
DOK1	-0.018	0.046	-10000	0	-0.38	2	2
JAK2	-0.054	0.11	-10000	0	-0.49	10	10
Jak2/Leptin Receptor/Leptin	-0.052	0.13	-10000	0	-0.52	9	9
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
PTPN1	-0.049	0.053	-10000	0	-0.37	6	6
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.008	0.13	-10000	0	-0.75	16	16
SRC	0	0.021	-10000	0	-10000	0	0
ITGB3	0.002	0.067	-10000	0	-0.75	4	4
CAT1/PTP1B	-0.23	0.13	-10000	0	-0.58	36	36
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)	-0.034	0.12	-10000	0	-0.61	3	3
negative regulation of transcription	-0.053	0.11	-10000	0	-0.48	10	10
FCGR2A	-0.023	0.18	-10000	0	-0.86	23	23
FER	-0.001	0.047	-10000	0	-0.76	2	2
alphaIIb/beta3 Integrin	-0.027	0.13	-10000	0	-0.64	22	22
BLK	-0.041	0.22	-10000	0	-0.86	33	33
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	0.033	-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	60	60
PRL	0.003	0.007	-10000	0	-10000	0	0
SOCS3	0.028	0.049	-10000	0	-0.73	2	2
SPRY2	0.001	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.043	-10000	0	-0.49	4	4
CSF1/CSF1R	-0.037	0.075	-10000	0	-0.53	10	10
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.01	0.067	-10000	0	-0.75	4	4
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.073	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	-0.008	0.069	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-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	-0.021	0.18	-10000	0	-0.85	22	22
SHC1	0.014	0.039	-10000	0	-0.86	1	1
NOX4	-0.006	0.074	-10000	0	-0.76	5	5

×

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

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
BAG4	0.014	0.033	-9999	-0.75	1	1
Caspase 8 (4 units)	-0.098	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	-0.072	0.31	-9999	-0.79	80	80
CYCS	-0.079	0.14	-9999	-0.43	1	1
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.37	0.48	-9999	-1	171	171
MAP2K7	-0.041	0.11	-9999	-10000	0	0
protein ubiquitination	0.06	0.071	-9999	-0.44	1	1
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	-0.093	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.051	0.12	-9999	-10000	0	0
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	-10000	0	0
MAPK8	-0.03	0.1	-9999	-0.51	1	1
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	-0.14	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.048	0.067	-9999	-10000	0	0
CHUK	0.061	0.075	-9999	-0.49	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.4	0.44	-9999	-0.75	279	279
TNF	0.003	0.1	-9999	-0.8	8	8
FASLG	-0.58	0.61	-9999	-1.1	279	279
NFKB1	0	0.055	-9999	-0.74	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.068	-9999	-0.52	9	9
CASP6	-0.048	0.052	-9999	-10000	0	0
CASP7	-0.062	0.21	-9999	-0.55	54	54
RELA	0.001	0.045	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.062	0.21	-9999	-0.55	54	54
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	54	54
BCL2	-0.017	0.098	-9999	-0.46	1	1

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.042	0.15	-9999	-0.58	38	38
EPHB2	0.001	0.11	-9999	-0.77	10	10
Syndecan-2/TACI	-0.056	0.17	-9999	-0.58	50	50
LAMA1	-0.007	0.13	-9999	-0.75	15	15
Syndecan-2/alpha2 ITGB1	-0.01	0.068	-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	-0.049	0.23	-9999	-0.86	38	38
BAX	0.054	0.02	-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	0.06	-9999	-0.56	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.005	0.055	-9999	-0.56	5	5
dendrite morphogenesis	-0.01	0.068	-9999	-0.5	10	10
Syndecan-2/GM-CSF	-0.017	0.097	-9999	-0.58	15	15
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.025	-9999	-0.58	1	1
GNB2L1	0.014	0.039	-9999	-0.86	1	1
MAPK3	0.022	0.094	-9999	-0.52	15	15
MAPK1	0.022	0.094	-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	0.008	0.074	-9999	-0.75	5	5
MAPK8	0.046	0.023	-9999	-0.47	1	1
Syndecan-2/alpha2/beta1 Integrin	-0.016	0.082	-9999	-0.65	2	2
Syndecan-2/Kininogen	-0.36	0.21	-9999	-0.48	386	386
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	0.056	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.042	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	0.043	-9999	-0.67	2	2
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.67	38	38
PRKCD	0.014	0.039	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.069	-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	-0.002	0.041	-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	50	50
RASA1	0.014	0.033	-9999	-0.75	1	1
alpha2/beta1 Integrin	-0.005	0.055	-9999	-0.56	5	5
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.086	-9999	-0.86	5	5
CASP3	0.043	0.025	-9999	-0.52	1	1
FN1	-0.049	0.23	-9999	-0.86	38	38
Syndecan-2/IL8	-0.037	0.14	-9999	-0.56	34	34
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.56	0.33	-9999	-0.75	386	386
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.018	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	34	34
MMP2	0.006	0.092	-9999	-0.84	6	6
IL8	-0.04	0.21	-9999	-0.84	34	34
calcineurin-NFAT signaling pathway	-0.056	0.17	-9999	-0.57	50	50

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	35	35
NT3 (dimer)/TRKB	-0.14	0.25	-10000	0	-0.54	131	131
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	69	69
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.045	0.21	-10000	0	-0.76	40	40
NTRK2	-0.13	0.3	-10000	0	-0.75	99	99
NTRK3	-0.03	0.18	-10000	0	-0.75	31	31
NT-4/5 (dimer)/TRKB	-0.14	0.25	-10000	0	-0.56	129	129
neuron apoptosis	0.14	0.18	0.62	36	-10000	0	36
SHC 2-3/Grb2	-0.16	0.2	-10000	0	-0.71	35	35
SHC1	0.014	0.039	-10000	0	-0.86	1	1
SHC2	-0.098	0.14	-10000	0	-0.53	31	31
SHC3	-0.16	0.24	-10000	0	-0.64	87	87
STAT3 (dimer)	0.012	0.068	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.084	0.2	-10000	0	-0.56	78	78
RIN/GDP	0.048	0.064	-10000	0	-0.32	1	1
GIPC1	0.014	0.033	-10000	0	-0.75	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.07	0.14	-10000	0	-0.63	13	13
RIN/GTP	-0.001	0.03	-10000	0	-0.68	1	1
CCND1	0.009	0.16	-10000	0	-0.78	20	20
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)	-0.004	0.093	-10000	0	-0.86	6	6
SHC/GRB2/SOS1	-0.001	0.025	-10000	0	-0.58	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.15	0.27	-10000	0	-0.6	129	129
TRKA/NEDD4-2	-0.045	0.16	-10000	0	-0.58	40	40
ELMO1	0.012	0.055	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.003	0.042	-10000	0	-0.55	3	3
NGF	-0.067	0.26	-10000	0	-0.86	49	49
HRAS	0.014	0.039	-10000	0	-0.86	1	1
DOCK1	0.014	0.033	-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	-0.001	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	-0.07	0.14	-10000	0	-0.6	15	15
mol:GDP	0.062	0.087	-10000	0	-0.48	2	2
NGF (dimer)	-0.067	0.26	-10000	0	-0.86	49	49
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	0.033	-10000	0	-0.75	1	1
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
BDNF (dimer)/TRKB	-0.17	0.26	-10000	0	-0.55	156	156
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.002	0.038	-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	0.092	-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	69	69
ubiquitin-dependent protein catabolic process	-0.092	0.21	-10000	0	-0.55	87	87
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	31	31
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	0.012	0.068	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.76	31	31
MAPK3	-0.1	0.26	-10000	0	-0.58	95	95
MAPK1	-0.1	0.26	-10000	0	-0.58	95	95
CDC42/GDP	0.055	0.063	-10000	0	-0.31	1	1
NTF3	0.005	0.092	-10000	0	-0.78	7	7
NTF4	-0.004	0.093	-10000	0	-0.86	6	6
NGF (dimer)/TRKA/FAIM	-0.091	0.21	-10000	0	-0.55	87	87
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	-0.08	0.16	-10000	0	-0.62	23	23
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0	0.14	-10000	0	-0.52	35	35
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.049	0.066	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.063	-10000	0	-0.31	1	1
NGF (dimer)/TRKA/GRIT	-0.093	0.21	-10000	0	-0.56	87	87
neuron projection morphogenesis	-0.022	0.14	-10000	0	-0.54	13	13
NGF (dimer)/TRKA/NEDD4-2	-0.092	0.21	-10000	0	-0.55	87	87
MAP2K1	0.053	0.024	-10000	0	-10000	0	0
NGFR	-0.045	0.22	-10000	0	-0.86	36	36
NGF (dimer)/TRKA/GIPC/GAIP	-0.054	0.12	-10000	0	-0.59	3	3
RAS family/GTP/PI3K	-0.002	0.029	-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	0.058	-10000	0	-0.75	3	3
MAPKKK cascade	-0.096	0.18	-10000	0	-0.61	45	45
RASA1	0.014	0.033	-10000	0	-0.75	1	1
TRKA/c-Abl	-0.044	0.15	-10000	0	-0.57	40	40
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.15	0.24	-10000	0	-0.5	157	157
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.079	0.18	-10000	0	-0.87	3	3
MATK	-0.073	0.26	-10000	0	-0.86	52	52
NEDD4L	0.014	0.033	-10000	0	-0.75	1	1
RAS family/GDP	-0.008	0.032	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.076	0.16	-10000	0	-0.47	38	38
Rac1/GTP	-0.045	0.085	-10000	0	-0.42	7	7
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

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	0.009	0.22	-10000	0	-0.56	18	18
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.086	0.12	-10000	0	-0.76	2	2
EDN1	-0.015	0.19	-10000	0	-0.77	18	18
EDN3	-0.019	0.16	-10000	0	-0.86	17	17
EDN2	-0.091	0.28	-10000	0	-0.82	66	66
HRAS/GDP	0.052	0.17	-10000	0	-0.7	9	9
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.022	0.15	-10000	0	-0.51	15	15
ADCY4	0.01	0.17	-10000	0	-0.74	3	3
ADCY5	-0.007	0.2	-10000	0	-0.69	14	14
ADCY6	0.009	0.17	-10000	0	-0.74	3	3
ADCY7	-0.005	0.19	-10000	0	-0.73	7	7
ADCY1	0	0.18	-10000	0	-0.74	4	4
ADCY2	-0.12	0.27	-10000	0	-0.71	29	29
ADCY3	0.01	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.27	-10000	0	-0.74	33	33
ADCY9	0.01	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.078	0.15	-10000	0	-0.57	7	7
ETB receptor/Endothelin-1/Gq/GTP	0.035	0.11	-10000	0	-0.46	11	11
GNAO1	0.007	0.084	-10000	0	-0.84	5	5
HRAS	0.014	0.039	-10000	0	-0.86	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.22	0.38	72	-0.83	3	75
ETA receptor/Endothelin-1/Gs/GTP	-0.013	0.21	0.36	72	-0.79	3	75
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.042	0.34	-10000	0	-0.95	52	52
EDNRB	0.007	0.069	-10000	0	-0.78	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.041	0.3	-10000	0	-0.75	48	48
CYSLTR1	0.008	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.013	0.11	-10000	0	-0.39	2	2
mol:GDP	0.045	0.18	-10000	0	-0.68	12	12
SLC9A3	-0.35	0.3	-10000	0	-0.53	324	324
RAF1	0.048	0.17	-10000	0	-0.71	9	9
JUN	0.088	0.12	-10000	0	-0.57	1	1
JAK2	0.009	0.22	-10000	0	-0.88	3	3
mol:IP3	0.018	0.17	-10000	0	-0.57	17	17
ETA receptor/Endothelin-1	-0.026	0.27	0.45	72	-0.57	53	125
PLCB1	0.003	0.1	-10000	0	-0.75	9	9
PLCB2	-0.081	0.28	-10000	0	-0.86	58	58
ETA receptor/Endothelin-3	-0.022	0.15	-10000	0	-0.68	19	19
FOS	0.06	0.2	-10000	0	-0.86	15	15
Gai/GDP	0.039	0.07	-10000	0	-0.63	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.003	0.24	-10000	0	-0.77	16	16
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
PRKCB1	0.02	0.16	-10000	0	-0.54	17	17
GNAQ	0.02	0.004	-10000	0	-10000	0	0
GNAZ	0.011	0.058	-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	0.045	0.14	-10000	0	-0.5	9	9
MAPK14	0.024	0.13	-10000	0	-0.6	8	8
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	0.058	-10000	0	-0.75	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.015	0.14	-10000	0	-0.54	14	14
ETB receptor/Endothelin-2	-0.086	0.21	-10000	0	-0.62	69	69
ETB receptor/Endothelin-3	-0.029	0.13	-10000	0	-0.66	20	20
ETB receptor/Endothelin-1	-0.032	0.16	-10000	0	-0.63	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	-0.06	0.19	-10000	0	-0.61	13	13
MAPK8	0.08	0.13	-10000	0	-0.59	3	3
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.03	0.091	-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	-0.71	8	8
COL1A2	-0.1	0.34	-10000	0	-0.89	67	67
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.081	0.23	-10000	0	-0.63	68	68
mol:DAG	0.018	0.17	-10000	0	-0.57	17	17
MAP2K2	0.057	0.18	-10000	0	-0.7	10	10
MAP2K1	0.058	0.17	-10000	0	-0.7	9	9
EDNRA	-0.008	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.02	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.035	0.14	-10000	0	-0.7	15	15
HRAS/GTP	0.036	0.17	-10000	0	-0.67	12	12
PRKCH	0.03	0.16	-10000	0	-0.6	12	12
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.03	0.16	-10000	0	-0.64	10	10
PRKCB	0.025	0.18	-10000	0	-0.71	13	13
PRKCE	0.028	0.16	-10000	0	-0.59	13	13
PRKCD	0.029	0.16	-10000	0	-0.64	10	10
PRKCG	0.003	0.2	-10000	0	-0.73	20	20
regulation of vascular smooth muscle contraction	0.059	0.23	-10000	0	-1	15	15
PRKCQ	0.017	0.18	-10000	0	-0.69	14	14
PLA2G4A	0.077	0.16	-10000	0	-0.63	7	7
GNA14	0.009	0.088	-10000	0	-0.75	7	7
GNA15	-0.007	0.15	-10000	0	-0.86	15	15
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.058	-10000	0	-0.74	3	3
Rac1/GTP	-0.013	0.22	0.38	72	-0.83	3	75
MMP1	-0.13	0.37	-10000	0	-0.85	102	102

×

Regulation of nuclear SMAD2/3 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
EP300	0.014	0.034	-10000	0	-0.73	1	1
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.021	0.087	-10000	0	-0.52	4	4
AKT1	0.02	0.006	-10000	0	-10000	0	0
GSC	-0.027	0.22	-10000	0	-0.76	43	43
NKX2-5	-0.048	0.22	-10000	0	-0.86	34	34
muscle cell differentiation	0.035	0.11	0.58	9	-10000	0	9
SMAD2-3/SMAD4/SP1	0.04	0.08	-10000	0	-10000	0	0
SMAD4	0.032	0.029	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.003	0.046	-10000	0	-0.53	3	3
SMAD3/SMAD4/VDR	0.011	0.05	-10000	0	-10000	0	0
MYC	-0.031	0.16	-10000	0	-0.86	19	19
CDKN2B	0.056	0.091	-10000	0	-0.68	6	6
AP1	0.06	0.075	-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	0.044	0.069	-10000	0	-0.48	2	2
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	44	44
SMAD3/SMAD4/GR	0.009	0.044	-10000	0	-0.6	1	1
GATA3	-0.35	0.38	-10000	0	-0.74	251	251
SKI/SIN3/HDAC complex/NCoR1	0.055	0.044	-10000	0	-10000	0	0
MEF2C/TIF2	-0.075	0.19	-10000	0	-0.81	20	20
endothelial cell migration	0.097	0.26	0.74	74	-10000	0	74
MAX	0.019	0.016	-10000	0	-10000	0	0
RBBP7	0.015	0.005	-10000	0	-10000	0	0
RBBP4	0.014	0.034	-10000	0	-0.75	1	1
RUNX2	-0.008	0.14	-10000	0	-0.86	14	14
RUNX3	-0.37	0.44	-10000	0	-0.86	225	225
RUNX1	-0.047	0.23	-10000	0	-0.86	37	37
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.017	0.042	-10000	0	-0.87	1	1
VDR	0.011	0.058	-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	44	44
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.004	-10000	0	-10000	0	0
SERPINE1	-0.099	0.26	-10000	0	-0.74	74	74
SMAD3/SMAD4/ATF2	0.008	0.037	-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	0.035	-10000	0	-0.45	1	1
JUN	0.075	0.072	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.012	0.11	-10000	0	-0.56	18	18
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	-0.094	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	275	275
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.006	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	-0.46	1	1
ZBTB17	-0.001	0.045	-10000	0	-0.72	2	2
LAMC1	0.071	0.041	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.031	-10000	0	-10000	0	0
IRF7	-0.014	0.16	-10000	0	-0.85	19	19
ESR1	0.002	0.071	-10000	0	-0.76	4	4
HNF4A	-0.049	0.21	-10000	0	-0.75	44	44
MEF2C	-0.007	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	-0.051	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	0.004	-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	0.019	-10000	0	-10000	0	0
SMAD3	0.033	0.026	-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	-0.52	1	1
NCOR1	0.015	0.005	-10000	0	-10000	0	0
NCOA2	0.003	0.1	-10000	0	-0.75	9	9
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.037	0.15	-10000	0	-0.67	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.085	-10000	0	-10000	0	0
IFNB1	0.045	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.012	0.21	-10000	0	-0.82	15	15
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	0.077	0.065	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.29	0.32	-10000	0	-0.61	247	247
SMAD7	0.1	0.08	-10000	0	-10000	0	0
MYC/MIZ-1	-0.026	0.13	-10000	0	-0.65	21	21
SMAD3/SMAD4	-0.021	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	0.067	-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	-0.87	20	20
FOXO3	0.037	0.009	-10000	0	-10000	0	0
FOXO1	0.037	0.008	-10000	0	-10000	0	0
FOXO4	0.037	0.008	-10000	0	-10000	0	0
heart looping	-0.007	0.22	-10000	0	-0.79	20	20
CEBPB	-0.003	0.13	-10000	0	-0.87	12	12
SMAD3/SMAD4/DLX1	-0.31	0.3	-10000	0	-0.58	275	275
MYOD1	-0.043	0.2	-10000	0	-0.86	29	29
SMAD3/SMAD4/HNF4	-0.034	0.14	-10000	0	-0.5	41	41
SMAD3/SMAD4/GATA3	-0.23	0.25	-10000	0	-0.84	15	15
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.24	0.28	-10000	0	-0.67	51	51
SMAD3/SMAD4/SP1-3	-0.005	0.043	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.013	0.05	-10000	0	-10000	0	0
SIN3B	0.015	0.005	-10000	0	-10000	0	0
SIN3A	0.015	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.078	0.22	-10000	0	-0.64	55	55
ITGB5	0.085	0.064	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.014	0.11	-10000	0	-0.5	19	19
AR	-0.02	0.16	-10000	0	-0.75	24	24
negative regulation of cell growth	0.066	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.025	0.14	-10000	0	-0.6	29	29
E2F5	0.014	0.033	-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	-0.66	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	0.077	0.043	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.007	0.068	-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	0.033	-10000	0	-0.75	1	1

×

EPO signaling pathway

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
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	-0.14	0.25	-9999	-10000	0	0
RAP1A	-0.094	0.22	-9999	-10000	0	0
GAB1	-0.094	0.22	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-10000	0	0
EPO	-0.29	0.42	-9999	-0.85	182	182
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	183	183
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.31	-9999	-0.65	182	182
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	-0.12	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	0.033	-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	182	182
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	182	182
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	-0.91	1	1
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	0.077	-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	-0.13	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	-0.13	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	0.077	-9999	-0.62	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.29	-9999	-0.88	29	29
BCL2	-0.02	0.18	-9999	-10000	0	0

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.013	0.16	-9999	-0.86	17	17
WNT4	-0.07	0.24	-9999	-0.75	58	58
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.058	-9999	-0.75	3	3
WNT11	-0.04	0.2	-9999	-0.76	37	37

×

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	-0.005	0.13	-10000	0	-0.86	11	11
GNB1/GNG2	-0.035	0.063	-10000	0	-0.22	15	15
AKT1	0.054	0.1	-10000	0	-0.25	1	1
EGF	-0.67	0.23	-10000	0	-0.75	466	466
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.033	0.081	-10000	0	-0.61	2	2
mol:Ca2+	0.04	0.14	-10000	0	-0.33	28	28
LYN	-0.03	0.071	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.038	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.049	0.16	-10000	0	-0.37	25	25
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	0.028	0.079	-10000	0	-0.42	7	7
G beta5/gamma2	-0.046	0.084	-10000	0	-0.3	16	16
PRKCH	0.042	0.16	-10000	0	-0.39	21	21
DNM1	-0.001	0.12	-10000	0	-0.86	10	10
TXA2/TP beta/beta Arrestin3	-0.013	0.041	-10000	0	-0.32	1	1
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.12	0.31	-10000	0	-0.86	77	77
G12 family/GTP	-0.043	0.092	-10000	0	-0.32	25	25
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	-0.003	0.12	-10000	0	-0.75	13	13
mol:IP3	0.037	0.17	-10000	0	-0.42	28	28
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.027	0.22	-10000	0	-0.59	28	28
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.055	0.13	-10000	0	-0.61	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.051	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.013	0.051	-10000	0	-0.8	2	2
PRKCB1	0.036	0.16	-10000	0	-0.38	42	42
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.034	0.21	-10000	0	-0.53	44	44
LCK	-0.047	0.12	-10000	0	-0.6	13	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.041	0.097	-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	-0.43	1	1
MAPK14	0.054	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.035	0.19	-10000	0	-0.48	30	30
MAPK11	0.053	0.11	-10000	0	-0.38	2	2
ARHGEF1	0.041	0.089	-10000	0	-0.33	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.043	0.17	-10000	0	-0.39	44	44
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.044	0.14	-10000	0	-0.35	20	20
cAMP biosynthetic process	0.034	0.16	-10000	0	-0.38	32	32
Gq family/GTP/EBP50	0.025	0.06	-10000	0	-0.28	3	3
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	-0.086	0.1	-10000	0	-0.41	15	15
VCAM1	0.043	0.14	-10000	0	-0.35	25	25
TP beta/Gq family/GDP/G beta5/gamma2	0.028	0.079	-10000	0	-0.42	7	7
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	79	79
Gq family/GDP/G beta5/gamma2	0.024	0.079	-10000	0	-0.41	7	7
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	-0.44	42	42
EGFR	0.001	0.11	-10000	0	-0.85	9	9
TXA2/TP alpha	0.032	0.21	-10000	0	-0.54	32	32
Gq family/GTP	-0.005	0.053	-10000	0	-0.26	7	7
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	77	77
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	-0.01	0.15	-10000	0	-0.86	15	15
PGK/cGMP	-0.012	0.076	-10000	0	-0.49	13	13
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.048	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	21	21
PRKCB	0.04	0.16	-10000	0	-0.43	22	22
PRKCE	0.043	0.16	-10000	0	-0.4	21	21
PRKCD	0.04	0.16	-10000	0	-0.41	22	22
PRKCG	0.028	0.19	-10000	0	-0.49	32	32
muscle contraction	0.042	0.2	-10000	0	-0.49	44	44
PRKCZ	0.049	0.16	-10000	0	-0.38	20	20
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.04	0.095	-10000	0	-10000	0	0
PRKCQ	0.034	0.17	-10000	0	-0.43	23	23
MAPKKK cascade	0.034	0.19	-10000	0	-0.49	29	29
SELE	0.036	0.16	-10000	0	-0.41	40	40
TP beta/GNAI2/GDP/G beta/gamma	-0.038	0.091	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.005	0.088	-10000	0	-0.75	7	7
chemotaxis	0.034	0.23	-10000	0	-0.61	43	43
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.011	0.058	-10000	0	-0.75	3	3
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.055	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	-0.097	0.16	-10000	0	-0.34	147	147
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.014	0.033	-10000	0	-0.74	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	0.077	-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	-0.09	0.28	-10000	0	-0.86	62	62
DKK1	-0.019	0.17	-10000	0	-0.83	21	21
beta catenin/beta TrCP1	0.084	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	0.008	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	0.008	-10000	0	-10000	0	0
CTNNB1	0.08	0.091	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.095	0.22	-10000	0	-0.57	86	86
HNF1A	-0.002	0.074	-10000	0	-0.75	5	5
CTBP1	0.005	0.008	-10000	0	-10000	0	0
MYC	0.004	0.14	-10000	0	-0.73	19	19
NKD1	-0.19	0.34	-10000	0	-0.75	138	138
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.037	0.12	-10000	0	-0.64	1	1
apoptosis	-0.097	0.16	-10000	0	-0.34	147	147
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	0.023	-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	0.032	-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	-0.091	0.22	-10000	0	-0.62	76	76
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	0.003	0.15	-10000	0	-0.73	20	20
WNT1	-0.028	0.19	-10000	0	-0.86	25	25
Axin1/APC/beta catenin	0.081	0.052	-10000	0	-10000	0	0
DKK2	-0.025	0.18	-10000	0	-0.83	25	25
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	-0.037	0.12	-10000	0	-0.66	1	1
PPP2R5D	0.093	0.16	0.36	137	-10000	0	137
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.03	0.12	-10000	0	-0.52	26	26
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0

×

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	0.044	-9999	-10000	0	0
GNAO1	0.01	0.084	-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	-0.025	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	0.058	-9999	-0.74	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.033	-9999	-0.74	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.054	0.049	-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	-0.023	0.13	-9999	-0.48	2	2
CXCR4	-0.12	0.26	-9999	-0.47	179	179
FLT1	0.01	0.086	-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	0.054	0.049	-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	-0.38	0.44	-9999	-0.86	233	233
S1P/S1P2/Gi	0.049	0.044	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	234	234
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.027	0.072	-9999	-10000	0	0
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.058	-9999	-0.74	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.005	0.088	-9999	-0.75	7	7
GNA15	-0.01	0.15	-9999	-0.86	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.058	-9999	-0.75	3	3
Rac1/GTP	-0.005	0.036	-9999	-0.49	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.015	0.087	-9999	-0.52	15	15
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.014	0.033	-9999	-0.75	1	1
ITGA4	-0.01	0.15	-9999	-0.86	15	15
alpha4/beta7 Integrin/MAdCAM1	-0.027	0.12	-9999	-0.52	27	27
EPO	-0.3	0.42	-9999	-0.86	182	182
alpha4/beta7 Integrin	-0.019	0.11	-9999	-0.67	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.11	-9999	-0.67	15	15
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.67	182	182
lamellipodium assembly	0	0.036	-9999	-0.53	2	2
PIK3CA	0.014	0.033	-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	0.17	-9999	-0.66	5	5
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
MADCAM1	-0.007	0.13	-9999	-0.86	12	12
cell adhesion	-0.027	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	0.015	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	-0.031	0.13	-9999	-0.56	29	29
p130Cas/Crk/Dock1	-0.024	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	0.026	0.12	-9999	-0.89	1	1
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.75	1	1
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0	0.037	-9999	-0.55	2	2

×

FoxO family signaling

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
G6PC	-0.57	0.68	-9999	-1.3	242	242
PLK1	-0.12	0.37	-9999	-0.8	93	93
CDKN1B	0.062	0.16	-9999	-10000	0	0
FOXO3	-0.038	0.23	-9999	-0.66	14	14
KAT2B	0.012	0.04	-9999	-0.78	1	1
FOXO1/SIRT1	-0.14	0.21	-9999	-0.4	2	2
CAT	-0.026	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	242	242
MAPK10	0.033	0.049	-9999	-0.43	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.047	-9999	-10000	0	0
response to oxidative stress	-0.029	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.028	0.2	-9999	-0.58	13	13
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	0.098	-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	0.043	0.097	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.037	0.028	-9999	-0.43	1	1
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	0.036	0.028	-9999	-10000	0	0
SOD2	0.014	0.2	-9999	-0.71	6	6
RBL2	0.023	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	0.033	-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	-0.73	262	262
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	-0.029	0.23	-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	0.043	-9999	-10000	0	0
SFN	-0.086	0.28	-9999	-0.83	62	62
CDK2	-0.018	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.012	0.099	-9999	-10000	0	0
CREBBP	-0.018	0.041	-9999	-10000	0	0
FBXO32	-0.026	0.22	-9999	-0.79	8	8
BCL6	0.025	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

×

LPA receptor mediated 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
GNB1/GNG2	-0.021	0.088	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
AP1	-0.03	0.1	-9999	-0.6	1	1
mol:PIP3	-0.026	0.091	-9999	-0.55	1	1
AKT1	-0.014	0.057	-9999	-10000	0	0
PTK2B	0.033	0.059	-9999	-10000	0	0
RHOA	0.037	0.035	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.051	0.052	-9999	-0.45	2	2
MAGI3	0.013	0.047	-9999	-0.75	2	2
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.021	0.085	-9999	-0.37	26	26
HRAS/GDP	-0.001	0.03	-9999	-0.68	1	1
positive regulation of microtubule depolymerization	0.046	0.069	-9999	-0.38	3	3
NF kappa B1 p50/RelA	-0.018	0.073	-9999	-10000	0	0
endothelial cell migration	0.007	0.13	-9999	-0.54	28	28
ADCY4	0.032	0.12	-9999	-0.47	24	24
ADCY5	0.023	0.13	-9999	-0.49	27	27
ADCY6	0.032	0.12	-9999	-0.47	24	24
ADCY7	0.027	0.12	-9999	-0.48	24	24
ADCY1	0.027	0.12	-9999	-0.48	25	25
ADCY2	-0.017	0.14	-9999	-0.52	25	25
ADCY3	0.032	0.12	-9999	-0.47	24	24
ADCY8	-0.027	0.14	-9999	-0.48	24	24
ADCY9	0.032	0.12	-9999	-0.47	24	24
GSK3B	0.042	0.056	-9999	-10000	0	0
arachidonic acid secretion	0.039	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	0.007	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	0.063	-9999	-1	2	2
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	0.051	0.053	-9999	-0.48	1	1
PLCB3	0.037	0.023	-9999	-0.43	1	1
FOS	-0.004	0.12	-9999	-0.76	13	13
positive regulation of mitosis	0.039	0.11	-9999	-0.44	22	22
LPA/LPA1-2-3	-0.025	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	0.033	-9999	-0.75	1	1
stress fiber formation	0.04	0.076	-9999	-10000	0	0
GNAZ	0.01	0.12	-9999	-0.48	25	25
EGFR/PI3K-beta/Gab1	-0.027	0.095	-9999	-0.57	1	1
positive regulation of dendritic cell cytokine production	-0.025	0.099	-9999	-0.44	26	26
LPA/LPA2/MAGI-3	-0.003	0.031	-9999	-0.48	2	2
ARHGEF1	0.031	0.095	-9999	-0.49	1	1
GNAI2	0.013	0.11	-9999	-0.47	22	22
GNAI3	0.013	0.11	-9999	-0.47	22	22
GNAI1	0.01	0.12	-9999	-0.48	25	25
LPA/LPA3	-0.007	0.06	-9999	-0.67	4	4
LPA/LPA2	-0.001	0.013	-9999	-10000	0	0
LPA/LPA1	-0.027	0.12	-9999	-0.51	28	28
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	253	253
HBEGF	-0.3	0.35	-9999	-0.67	247	247
mol:DAG	0.051	0.053	-9999	-0.48	1	1
cAMP biosynthetic process	0.02	0.12	-9999	-0.46	26	26
NFKB1	0.014	0.033	-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	0.077	-9999	-0.86	4	4
LPAR1	-0.012	0.15	-9999	-0.73	22	22
IL8	-0.08	0.2	-9999	-0.49	44	44
PTK2	0.024	0.1	-9999	-0.48	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.022	0.085	-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	0.088	-9999	-0.42	22	22
PI3K-beta	-0.016	0.067	-9999	-0.52	1	1
cell migration	-0.009	0.034	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-9999	-0.75	1	1
PXN	0.04	0.077	-9999	-10000	0	0
HRAS/GTP	-0.026	0.098	-9999	-0.45	22	22
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	247	247
PRKCE	0.013	0.034	-9999	-0.75	1	1
PRKCD	0.059	0.055	-9999	-10000	0	0
Gi(beta/gamma)	-0.025	0.097	-9999	-0.44	24	24
mol:LPA	0.004	0.023	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.017	0.081	-9999	-10000	0	0
MAPKKK cascade	0.039	0.11	-9999	-0.44	22	22
contractile ring contraction involved in cytokinesis	0.037	0.035	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.009	0.059	-9999	-0.4	11	11
GNA15	-0.016	0.079	-9999	-0.42	18	18
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.046	0.07	-9999	-0.39	3	3
GNA11	-0.006	0.046	-9999	-0.39	7	7
Rac1/GTP	-0.002	0.057	-9999	-0.91	2	2
MMP2	0.007	0.13	-9999	-0.54	28	28

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0.047	-9999	-0.75	2	2
SPHK1	-0.057	0.24	-9999	-0.86	43	43
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.001	0.095	-9999	-0.31	45	45
GNAO1	0.007	0.084	-9999	-0.84	5	5
mol:Sphinganine-1-P	-0.029	0.2	-9999	-0.66	45	45
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	0.033	-9999	-0.75	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.023	0.074	-9999	-10000	0	0
S1PR5	-0.13	0.33	-9999	-0.86	88	88
S1PR4	-0.028	0.19	-9999	-0.86	26	26
GNAI1	0.011	0.058	-9999	-0.75	3	3
S1P/S1P5/G12	-0.11	0.21	-9999	-0.54	88	88
S1P/S1P3/Gq	0.023	0.097	-9999	-0.42	16	16
S1P/S1P4/Gi	0.025	0.096	-9999	-0.38	12	12
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.058	-9999	-0.75	3	3
GNA14	0.005	0.088	-9999	-0.75	7	7
GNA15	-0.01	0.15	-9999	-0.86	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.058	-9999	-0.75	3	3
ABCC1	0.016	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	-0.015	0.16	-9999	-0.86	18	18
PLK4	0.011	0.067	-9999	-0.86	3	3
regulation of centriole replication	0.003	0.14	-9999	-0.67	21	21

×

Ceramide signaling pathway

Figure S68. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S68. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.033	-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	80	80
BAX	-0.042	0.018	-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	0.057	-10000	0	-0.59	4	4
EGF	-0.67	0.23	-10000	0	-0.75	466	466
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	0.037	-10000	0	-10000	0	0
cell proliferation	-0.052	0.06	-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	0.052	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.065	0.052	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.097	0.036	-10000	0	-0.26	1	1
FADD	0.025	0.094	-10000	0	-0.48	1	1
KSR1	-0.1	0.06	-10000	0	-0.63	4	4
MAPK8	-0.076	0.04	-10000	0	-0.35	3	3
PRKRA	-0.096	0.038	-10000	0	-10000	0	0
PDGFA	0.014	0.033	-10000	0	-0.75	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.006	0.094	-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	0.033	-10000	0	-0.75	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.024	-10000	0	-0.56	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.055	0.066	-10000	0	-0.5	10	10
PRKCD	0.014	0.039	-10000	0	-0.86	1	1
PRKCZ	0.011	0.058	-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	0.033	-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	0.068	-10000	0	-0.52	9	9
mol:Sphingosine-1-phosphate	0.027	0.045	-10000	0	-0.56	3	3
MAP2K1	-0.071	0.054	-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	0.023	-10000	0	-0.23	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-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	0.065	-10000	0	-0.53	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.037	-10000	0	-10000	0	0
MAP2K2	-0.071	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	0.049	-10000	0	-0.56	4	4
mol:PHOSPHOCHOLINE	0.23	0.083	0.26	468	-10000	0	468
NF kappa B1/RelA/I kappa B alpha	-0.004	0.038	-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

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.019	-10000	0	-10000	0	0
AES	0.005	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	25	25
TLE1	0.005	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.001	-10000	0	-10000	0	0
CTNNB1	0.048	0.1	-10000	0	-0.45	1	1
WIF1	-0.001	0.076	-10000	0	-0.77	5	5
beta catenin/RanBP3	0.004	0.1	0.36	19	-10000	0	19
KREMEN2	-0.09	0.28	-10000	0	-0.86	62	62
DKK1	-0.019	0.17	-10000	0	-0.83	21	21
beta catenin/beta TrCP1	0.056	0.094	-10000	0	-10000	0	0
FZD1	0.016	0.003	-10000	0	-10000	0	0
AXIN2	0.009	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	0.018	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.073	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.04	0.083	0.25	2	-10000	0	2
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.003	0.075	-10000	0	-0.74	5	5
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.008	0.15	-10000	0	-0.75	19	19
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.095	0.22	-10000	0	-0.57	86	86
NKD1	-0.19	0.34	-10000	0	-0.75	138	138
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	25	25
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.11	0.36	39	-10000	0	39
LEF1	-0.02	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	-0.091	0.22	-10000	0	-0.62	76	76
LRP6	0.016	0.002	-10000	0	-10000	0	0
CSNK1A1	0.005	0.019	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.009	0.15	-10000	0	-0.75	20	20
WNT1	-0.028	0.19	-10000	0	-0.86	25	25
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.016	0.002	-10000	0	-10000	0	0
FRAT1	0.014	0.004	-10000	0	-10000	0	0
PPP2R5D	0.096	0.16	0.35	137	-10000	0	137
APC	-0.017	0.11	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.012	0.064	0.27	5	-10000	0	5
CREBBP	0.005	0.017	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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	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	-0.024	0.066	0.25	6	-10000	0	6
FASLG/FAS/FADD/FAF1	-0.14	0.16	-10000	0	-0.35	22	22
MAP2K4	-0.086	0.16	-10000	0	-0.43	23	23
mol:ceramide	-0.15	0.2	-10000	0	-0.48	32	32
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	0.018	0.066	-10000	0	-10000	0	0
MAP3K1	-0.036	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	-0.037	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	-0.066	0.077	-10000	0	-0.71	1	1
MAPK8	-0.085	0.18	-10000	0	-0.52	24	24
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	0.056	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.045	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	-0.65	1	1
FASLG	-0.43	0.44	-10000	0	-0.87	262	262
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	0.003	0.1	-10000	0	-0.75	9	9
CASP8	0.028	0.1	0.4	36	-10000	0	36
IL6	-0.13	0.34	-10000	0	-0.96	65	65
MET	0.007	0.086	-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	32	32
activation of caspase activity by cytochrome c	0.018	0.066	-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 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
ARF5/GTP	-0.001	0.017	-9999	-10000	0	0
DAPP1	0.03	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	-0.07	0.15	-9999	-0.32	61	61
HRAS	0.015	0.038	-9999	-0.86	1	1
RAP1A	0.017	0.001	-9999	-10000	0	0
ARF5/GDP	0.018	0.074	-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	0.033	-9999	-0.75	1	1
ZAP70	-0.46	0.44	-9999	-0.86	281	281
mol:IP3	-0.036	0.11	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.018	0.074	-9999	-10000	0	0
RhoA/GDP	-0.004	0.017	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.021	-9999	-0.48	1	1
BLNK	0.014	0.033	-9999	-0.75	1	1
actin cytoskeleton reorganization	0.045	0.082	-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	129	129
BLK	-0.041	0.22	-9999	-0.86	33	33
PDPK1	0.014	0.033	-9999	-0.75	1	1
CYTH1	-0.001	0.018	-9999	-10000	0	0
HCK	-0.032	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	-0.55	1	1
SGK1	-0.001	0.026	-9999	-0.6	1	1
INPP5D	0.009	0.077	-9999	-0.86	4	4
mol:GDP	0.01	0.078	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.013	0.047	-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	-0.2	0.38	-9999	-0.86	124	124
mol:PI-3-4-P2	0.025	0.061	-9999	-0.67	4	4
RAS family/GTP/PI3K Class I	-0.001	0.019	-9999	-10000	0	0
PLEKHA1	0.036	0.054	-9999	-0.57	4	4
Rac1/GDP	0.018	0.074	-9999	-10000	0	0
LAT	-0.23	0.4	-9999	-0.86	145	145
Rac1/GTP	-0.001	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	-0.021	0.18	-9999	-0.85	22	22
BTK	-0.097	0.19	-9999	-10000	0	0

×

E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.022	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	0.058	-9999	-0.75	3	3
CDH1	-0.015	0.15	-9999	-0.75	21	21

×

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	-0.16	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.029	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.11	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	-0.81	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.28	0.29	-9999	-0.74	113	113
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	-0.07	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	0.22	-9999	-1	2	2
STAT1	-0.15	0.24	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.38	0.43	-9999	-0.85	237	237
PIK3CA	0.014	0.033	-9999	-0.75	1	1
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.076	0.084	-9999	-0.47	1	1
mol:Ca2+	-0.2	0.21	-9999	-10000	0	0
MAPK3	-0.091	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.091	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.014	0.033	-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	0.082	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.18	0.19	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.86	237	237
apoptosis	-0.038	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	173	173
CAMK2B	-0.1	0.28	-9999	-0.76	78	78
FRAP1	-0.11	0.2	-9999	-10000	0	0
PRKCD	-0.12	0.22	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.11	0.09	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.015	0.033	-9999	-0.74	1	1
IRF1	-0.061	0.19	-9999	-0.93	1	1
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.011	0.083	-9999	-0.73	6	6
mol:GDP	-0.16	0.17	-9999	-10000	0	0
CASP1	-0.021	0.082	-9999	-10000	0	0
PTGES2	0.013	0.047	-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	-0.11	0.09	-9999	-0.37	1	1
PTPN11	-0.17	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.02	0.092	-10000	0	-0.44	24	24
regulation of S phase of mitotic cell cycle	-0.014	0.068	-10000	0	-0.62	1	1
GNAO1	0.008	0.084	-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	53	53
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.047	0.091	-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	0.058	-10000	0	-0.75	3	3
mol:GDP	-0.026	0.12	-10000	0	-0.56	24	24
cell proliferation	0.071	0.11	-10000	0	-0.64	4	4
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
FOS	0.056	0.15	-10000	0	-0.81	13	13
mol:Ca2+	-0.003	0.014	-10000	0	-0.11	4	4
MAPK3	0.063	0.1	-10000	0	-0.57	4	4
MAPK1	0.045	0.054	-10000	0	-0.29	4	4
PIK3R1	0.014	0.033	-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	53	53
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	13	13
HRAS/GTP	-0.019	0.085	-10000	0	-0.45	5	5
actin cytoskeleton reorganization	-0.001	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	0.03	-10000	0	-0.49	2	2
apoptosis	-0.061	0.095	0.43	12	-10000	0	12
T-DHT/AR/PELP1	-0.023	0.1	-10000	0	-0.49	24	24
HRAS/GDP	-0.025	0.12	-10000	0	-0.53	25	25
CREB1	0.061	0.1	-10000	0	-0.47	12	12
RAC1-CDC42/GTP	-0.001	0.024	-10000	0	-10000	0	0
AR	-0.019	0.16	-10000	0	-0.75	24	24
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.036	0.093	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.023	0.1	-10000	0	-0.49	24	24
T-DHT/AR/PELP1/Src	-0.02	0.092	-10000	0	-0.44	24	24
MAP2K2	0.047	0.093	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.015	0.068	-10000	0	-0.63	1	1
GNAZ	0.011	0.058	-10000	0	-0.75	3	3
SHBG	-0.063	0.23	-10000	0	-0.75	53	53
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	-0.18	0.31	-10000	0	-0.68	142	142
Gi family/GTP	-0.013	0.058	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.031	0.002	-9999	-10000	0	0
SMARCC1	0.026	0.01	-9999	-10000	0	0
REL	0.009	0.058	-9999	-0.74	3	3
HDAC7	-0.097	0.087	-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	0.047	-9999	-0.59	3	3
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.089	-9999	-0.68	4	4
MAP2K6	-0.002	0.059	-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	-1.2	5	5
NCOA2	0.002	0.1	-9999	-0.75	9	9
CEBPA	-0.001	0.12	-9999	-0.86	10	10
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.092	0.095	-9999	-0.55	2	2
NR0B1	-0.053	0.22	-9999	-0.86	34	34
EGR1	-0.001	0.11	-9999	-0.75	11	11
RXRs/9cRA	-0.004	0.047	-9999	-0.54	4	4
AR/RACK1/Src	-0.015	0.061	-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	0.003	0.029	-9999	-0.59	1	1
T-DHT/AR/TIF2/CARM1	-0.019	0.089	-9999	-0.81	3	3
SRC	0.003	0.047	-9999	-10000	0	0
NR3C1	0.014	0.039	-9999	-0.86	1	1
KLK3	-0.053	0.19	-9999	-0.72	27	27
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.025	0.054	-9999	-0.62	2	2
TMPRSS2	-0.96	0.38	-9999	-1.1	449	449
RXRG	0.006	0.077	-9999	-0.87	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	-0.023	0.13	-9999	-0.63	20	20
AR	-0.009	0.084	-9999	-0.42	12	12
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	104	104
T-DHT/AR/RACK1/Src	-0.015	0.059	-9999	-0.6	2	2
positive regulation of transcription	-0.002	0.11	-9999	-0.74	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	0.02	0.07	-9999	-0.67	3	3
T-DHT/AR/Hsp90	-0.026	0.053	-9999	-0.59	3	3
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.011	0.05	-9999	-0.51	2	2
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.014	0.008	-9999	-10000	0	0
POU2F1	0.005	0.014	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.067	0.14	-9999	-0.61	27	27
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-10000	0	0
epithelial cell differentiation	-0.051	0.11	-10000	0	-0.57	1	1
ITCH	0.055	0.018	-10000	0	-10000	0	0
WWP1	-0.096	0.067	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	0.001	0.11	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.018	0.08	-10000	0	-0.57	1	1
PTPRZ1	-0.082	0.25	-10000	0	-0.76	63	63
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.053	0.073	-10000	0	-0.6	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.083	0.094	-10000	0	-0.57	9	9
ADAM17	0.055	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.086	-10000	0	-0.46	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.63	11	11
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.076	0.077	-10000	0	-0.54	9	9
GRIN2B	-0.057	0.091	-10000	0	-0.61	3	3
ErbB4/ErbB2/betacellulin	-0.13	0.16	-10000	0	-0.52	70	70
STAT1	0.014	0.039	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.084	0.26	-10000	0	-0.75	68	68
E4ICDs/ETO2	-0.11	0.08	-10000	0	-0.6	3	3
axon guidance	-0.017	0.072	-10000	0	-10000	0	0
NEDD4	0.052	0.052	-10000	0	-0.73	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.074	0.19	-10000	0	-0.57	68	68
CBFA2T3	0.012	0.055	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.064	0.038	-10000	0	-0.52	1	1
MAPK3	-0.029	0.082	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.11	0.073	-10000	0	-0.54	1	1
MAPK1	-0.029	0.082	-10000	0	-0.6	1	1
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.077	0.081	-10000	0	-0.53	10	10
NRG1	0.036	0.11	-10000	0	-0.56	16	16
NRG3	-0.003	0.13	-10000	0	-0.86	11	11
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
NRG4	-0.057	0.22	-10000	0	-0.77	47	47
heart development	-0.017	0.072	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.08	-10000	0	-0.53	10	10
ERBB2	0.052	0.04	-10000	0	-0.56	2	2
WWOX/E4ICDs	-0.11	0.075	-10000	0	-0.7	1	1
SHC1	0.014	0.039	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.15	0.15	-10000	0	-0.57	51	51
apoptosis	0.1	0.063	0.39	7	-10000	0	7
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.089	-10000	0	-0.52	11	11
ErbB4/ErbB2/epiregulin	-0.098	0.13	-10000	0	-0.57	34	34
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.18	-10000	0	-0.59	78	78
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.13	0.14	-10000	0	-0.73	1	1
MDM2	-0.1	0.074	-10000	0	-0.4	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.054	0.077	-10000	0	-0.52	9	9
STAT5A	-0.005	0.067	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.084	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	-0.67	1	1
E4ICDs/TAB2/NCoR1	-0.1	0.048	-10000	0	-0.38	1	1
STAT5A (dimer)	-0.054	0.12	-10000	0	-0.62	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.064	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.041	0.21	-10000	0	-0.86	33	33
BTC	-0.098	0.27	-10000	0	-0.75	77	77
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.072	-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	-0.11	0.13	-10000	0	-0.51	44	44
glial cell differentiation	0.1	0.048	0.37	1	-10000	0	1
WWOX	0.014	0.039	-10000	0	-0.86	1	1
cell proliferation	-0.075	0.16	-10000	0	-0.59	14	14

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.045	0.092	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	88	88
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.007	0.084	-9999	-0.84	5	5
RhoA/GTP	-0.046	0.094	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.014	0.12	-9999	-10000	0	0
GNAZ	0.011	0.058	-9999	-0.75	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.13	0.33	-9999	-0.86	88	88
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	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	0.058	-9999	-0.75	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.004	0.049	-9999	-0.56	4	4
AKT1	-0.055	0.2	-9999	-0.71	3	3
PTK2B	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.002	0.041	-9999	-0.83	1	1
CAV1	-0.047	0.23	-9999	-0.86	37	37
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.23	0.25	-9999	-1.2	1	1
endothelial cell proliferation	-0.041	0.2	-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	-0.24	0.26	-9999	-0.52	233	233
SHC1	0.014	0.039	-9999	-0.86	1	1
SHC2	0.008	0.082	-9999	-0.82	5	5
HRAS/GDP	-0.17	0.19	-9999	-0.83	2	2
SH2D2A	-0.27	0.41	-9999	-0.86	168	168
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	66	66
VEGFR1 homodimer	0.007	0.086	-9999	-0.86	5	5
SHC/GRB2/SOS1	-0.19	0.21	-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	-0.085	0.094	-9999	-0.58	1	1
HIF1A	0.013	0.047	-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	-0.23	0.25	-9999	-1.2	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.063	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.053	0.18	-9999	-0.57	1	1
PIK3R1	0.014	0.033	-9999	-0.75	1	1
mol:IP3	-0.16	0.27	-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	-0.38	0.44	-9999	-0.86	233	233
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	-0.22	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	-0.063	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.23	0.25	-9999	-1.2	1	1
VEGFR2/3 heterodimer	-0.002	0.041	-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	0.044	0.05	-9999	-0.73	2	2
FLT1	0.007	0.086	-9999	-0.86	5	5
NEDD4	0.015	0.047	-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	238	238
VEGFR1/2 heterodimer	-0.008	0.069	-9999	-0.61	6	6
KDR	0.044	0.05	-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	-0.78	2	2
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	-0.17	0.27	-9999	-1	2	2
GAB1	-0.17	0.19	-9999	-0.81	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.23	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	-0.083	0.2	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.23	0.25	-9999	-1.2	1	1
PI3K/GAB1	-0.055	0.2	-9999	-0.69	2	2
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	0.044	-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	-0.39	0.33	-9999	-1	66	66
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.27	-9999	-1.1	1	1
CaM/Ca2+	-0.19	0.2	-9999	-1	1	1
MAP2K3	-0.15	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	-0.23	0.25	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.23	0.25	-9999	-1.2	1	1
cell migration	-0.052	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	-0.063	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	0.014	0.033	-9999	-0.75	1	1
ITGB3	0.01	0.067	-9999	-0.75	4	4
NOS3	-0.074	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	-0.15	0.25	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.22	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	238	238
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	0.033	-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	-0.073	0.2	-9999	-0.65	6	6

×

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	0.058	-9999	-10000	0	0
epithelial cell differentiation	-0.016	0.079	-9999	-10000	0	0
CYFIP2	0.004	0.094	-9999	-0.75	8	8
ENAH	0.079	0.065	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.75	1	1
MYO6	0.032	0.097	-9999	-0.78	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.059	-9999	-0.48	8	8
AQP5	-0.17	0.24	-9999	-0.52	159	159
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.035	0.083	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.018	0.12	-9999	-0.49	15	15
EGF	-0.67	0.23	-9999	-0.75	466	466
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.051	0.16	-9999	-0.57	38	38
cortical microtubule organization	-0.016	0.079	-9999	-10000	0	0
GO:0000145	0.035	0.079	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.08	-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	0.051	0.084	-9999	-0.58	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.035	0.084	-9999	-10000	0	0
ARF6/GTP	-0.002	0.032	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.75	21	21
EGFR/EGFR/EGF/EGF	-0.35	0.14	-9999	-0.77	27	27
RhoA/GDP	-0.015	0.073	-9999	-10000	0	0
actin cytoskeleton organization	0.042	0.092	-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	0.006	0.094	-9999	-0.86	6	6
DIAPH1	-0.01	0.086	-9999	-0.7	8	8
Wnt receptor signaling pathway	0.016	0.079	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.063	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.042	0.094	-9999	-0.74	2	2
EFNA1	0.014	0.039	-9999	-0.86	1	1
LPP	0.044	0.089	-9999	-0.8	1	1
Ephrin A1/EPHA2	-0.016	0.074	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.062	-9999	-10000	0	0
MGAT3	0.018	0.12	-9999	-0.5	15	15
HGF/MET	-0.037	0.13	-9999	-0.96	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	0.07	-9999	-10000	0	0
KIAA1543	0.037	0.12	-9999	-0.86	6	6
KIFC3	0.034	0.086	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.75	1	1
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.033	0.093	-9999	-0.87	1	1
NCK1/GIT1	-0.001	0.025	-9999	-0.56	1	1
mol:GDP	-0.016	0.079	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.035	0.084	-9999	-10000	0	0
PIP5K1C	0.035	0.084	-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	0.059	0.12	-9999	-0.79	7	7
IGF-1R heterotetramer/IGF1	-0.02	0.084	-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	0.086	-9999	-0.86	5	5
PLEKHA7	0.032	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	0.071	0.076	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.058	-9999	-10000	0	0
regulation of cell-cell adhesion	0.042	0.092	-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

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.007	0.084	-9999	-0.84	5	5
CDC42/GTP	-0.017	0.061	-9999	-10000	0	0
PLCG1	0.035	0.077	-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	-0.017	0.06	-9999	-10000	0	0
S1PR5	-0.13	0.33	-9999	-0.86	88	88
S1PR4	-0.028	0.19	-9999	-0.86	26	26
MAPK3	0.035	0.077	-9999	-10000	0	0
MAPK1	0.035	0.077	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
GNAI1	0.011	0.058	-9999	-0.75	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	88	88
RHOA	0.016	0.12	-9999	-0.49	26	26
S1P/S1P4/Gi	-0.019	0.07	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.058	-9999	-0.75	3	3
S1P/S1P4/G12/G13	-0.027	0.12	-9999	-0.53	26	26
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.031	0.12	-9999	-0.51	32	32
RGS9BP	-0.019	0.16	-9999	-0.75	23	23
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.013	0.085	-9999	-0.59	11	11
mol:ADP	0.012	0.044	-9999	-0.68	2	2
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.037	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.026	-9999	-0.59	1	1
GRK7	0.008	0.055	-9999	-0.86	2	2
CNGB3	-0.007	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	-0.034	0.12	-9999	-0.58	5	5
Cone Metarhodopsin II	-0.002	0.034	-9999	-0.55	2	2
Na + (4 Units)	-0.019	0.11	-9999	-0.64	15	15
GNAT2/GDP	-0.031	0.11	-9999	-0.5	9	9
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.043	-9999	-0.54	3	3
Cone Transducin	-0.033	0.13	-9999	-0.54	32	32
SLC24A2	-0.009	0.1	-9999	-0.86	7	7
GNB3/GNGT2	-0.041	0.16	-9999	-0.67	32	32
GNB3	-0.038	0.21	-9999	-0.86	31	31
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0	0.066	-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	0.086	-9999	-0.6	11	11
mol:Pi	-0.036	0.13	-9999	-0.5	38	38
Cone CNG Channel	-0.013	0.085	-9999	-0.55	9	9
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.009	0.1	-9999	-0.86	7	7
RGS9	-0.008	0.14	-9999	-0.82	15	15
PDE6C	0.004	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

×

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	-0.019	0.11	-9999	-0.67	15	15
alpha4/beta1 Integrin	-0.019	0.11	-9999	-0.67	15	15

×

Noncanonical Wnt signaling 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
NFATC2	0.011	0.061	-9999	-0.78	3	3
GNB1/GNG2	-0.054	0.11	-9999	-0.53	8	8
mol:DAG	0.01	0.13	-9999	-10000	0	0
PLCG1	0.009	0.13	-9999	-10000	0	0
YES1	-0.011	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	-0.05	0.1	-9999	-10000	0	0
MAP3K7	-0.095	0.22	-9999	-0.69	7	7
mol:Ca2+	0.01	0.13	-9999	-10000	0	0
mol:IP3	0.01	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	48	48
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.011	0.14	-9999	-0.56	8	8
GO:0007205	0.011	0.13	-9999	-10000	0	0
WNT6	-0.013	0.16	-9999	-0.86	17	17
WNT4	-0.07	0.24	-9999	-0.75	58	58
NFAT1/CK1 alpha	-0.049	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.058	-9999	-0.75	3	3
WNT11	-0.04	0.2	-9999	-0.76	37	37
CDC42	0	0.14	-9999	-0.52	8	8

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.012	0.036	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.035	0.096	-9999	-0.48	7	7
JUN	0.027	0.11	-9999	-0.55	7	7
HRAS	0.014	0.039	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.051	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	-0.051	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	44	44
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.045	0.14	-9999	-0.83	5	5
GRB7	0.005	0.088	-9999	-0.75	7	7
RET51/GFRalpha1/GDNF	-0.051	0.16	-9999	-0.68	12	12
MAPKKK cascade	-0.041	0.12	-9999	-0.71	6	6
BCAR1	0.014	0.033	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.039	0.13	-9999	-0.47	43	43
lamellipodium assembly	-0.033	0.091	-9999	-0.44	7	7
RET51/GFRalpha1/GDNF/SHC	-0.052	0.16	-9999	-0.67	13	13
PIK3CA	0.014	0.033	-9999	-0.75	1	1
RET9/GFRalpha1/GDNF/SHC	-0.037	0.12	-9999	-0.46	41	41
RET9/GFRalpha1/GDNF/Shank3	-0.036	0.12	-9999	-0.46	40	40
MAPK3	0.007	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	-0.007	0.13	-9999	-0.76	15	15
GFRA1	-0.039	0.2	-9999	-0.76	37	37
MAPK8	0.016	0.12	-9999	-0.58	7	7
HRAS/GTP	-0.047	0.14	-9999	-0.84	6	6
tube development	-0.033	0.11	-9999	-0.5	6	6
MAPK1	0.007	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	0.077	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.057	0.17	-9999	-0.87	12	12
SHC1	0.014	0.039	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.051	0.16	-9999	-0.7	11	11
RET51/GFRalpha1/GDNF/Dok5	-0.064	0.19	-9999	-0.8	19	19
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	0.033	-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	-0.013	0.15	-9999	-0.76	19	19
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.027	0.11	-9999	-0.53	7	7
RET9/GFRalpha1/GDNF/FRS2	-0.036	0.12	-9999	-0.46	40	40
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.75	1	1
NCK1	0.014	0.033	-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	7	7
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	-0.051	0.16	-9999	-0.7	11	11
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.067	-9999	-0.75	4	4
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	-0.051	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	0.066	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.054	0.16	-9999	-0.7	13	13
Rac1/GTP	-0.039	0.11	-9999	-0.54	7	7
RET9/GFRalpha1/GDNF	-0.039	0.14	-9999	-0.51	40	40
GFRalpha1/GDNF	-0.045	0.16	-9999	-0.58	40	40

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.37	-9999	-0.75	199	199
HRAS	0.014	0.039	-9999	-0.86	1	1
EGFR	0.001	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	0.086	-9999	-0.86	5	5
PIK3CA	0.014	0.033	-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	-0.041	0.097	-9999	-0.38	5	5
ERBB2	0.013	0.047	-9999	-0.75	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.022	0.092	-9999	-0.29	6	6
PIK3R1	0.014	0.033	-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

×

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	0.075	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.16	0.29	-9999	-0.67	123	123
NFKBIA	0.063	0.02	-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	0.085	-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	0.078	-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	-0.035	0.062	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.19	0.37	-9999	-0.86	123	123
NFKB1	0.019	0.033	-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	0.033	-9999	-0.75	1	1
TNF/TNFR1A	-0.009	0.076	-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	0.02	-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	-0.039	0.07	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.036	0.064	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.014	0.033	-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	0.043	0.67	2	-10000	0	2
CDKN1A	-0.003	0.04	-10000	0	-0.65	2	2
KAT2B	0.014	0.033	-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	-0.33	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.006	0.13	-10000	0	-0.86	11	11
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.018	0.16	-10000	0	-0.66	30	30
PPARGC1A	-0.059	0.23	-10000	0	-0.75	51	51
FHL2	0.008	0.077	-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	0.043	-10000	0	-0.67	2	2
SIRT1/FOXO3a	0.001	0.016	0.32	1	-10000	0	1
SIRT1	0.001	0.01	-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	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.048	0.14	-10000	0	-0.49	51	51
p53/SIRT1	0.001	0.023	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	-0.46	5	5
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	0.033	0.13	0.57	30	-10000	0	30
TP53	0.001	0.01	-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	-0.014	0.097	-10000	0	-0.67	11	11
ACSS2	0.028	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.033	0.13	-10000	0	-0.57	30	30

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.058	-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	-0.085	0.22	-9999	-0.62	71	71
IL1A	-0.007	0.13	-9999	-0.86	12	12
IL1B	0.023	0.073	-9999	-0.65	6	6
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-10000	0	0
IL1R2	-0.077	0.26	-9999	-0.79	60	60
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.003	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	0.04	0.047	-9999	-10000	0	0
JUN	0.06	0.034	-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	-0.52	15	15
PIK3R1	0.014	0.033	-9999	-0.75	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.015	0.083	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	-0.01	0.069	-9999	-0.52	8	8
NFKB1	0.014	0.033	-9999	-0.75	1	1
MAPK8	0.051	0.036	-9999	-10000	0	0
IRAK1	0.031	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.022	0.12	-9999	-0.67	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	-0.004	0.032	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.01	0.069	-9999	-0.52	8	8
IL1 beta/IL1R2	-0.066	0.17	-9999	-0.52	66	66
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.01	0.07	-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	0.099	-9999	-0.57	16	16
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	-0.84	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	-0.091	0.22	-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	0.033	-9999	-0.75	1	1
IL1RN	-0.013	0.16	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.043	0.032	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
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	0.034	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.023	0.12	-10000	0	-0.67	18	18
mol:Ca2+	-0.016	0.16	0.41	18	-0.65	24	42
AGT	-0.023	0.18	-10000	0	-0.82	24	24
CCNA2	-0.056	0.23	-10000	0	-0.88	6	6
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.02	0.084	-10000	0	-0.55	11	11
CDK2/Cyclin E1	-0.01	0.057	-10000	0	-0.47	7	7
MAPK3	0.007	0.13	-10000	0	-0.67	18	18
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.007	0.13	-10000	0	-0.67	18	18
PTP4A1	0.042	0.067	-10000	0	-10000	0	0
PTP4A3	-0.015	0.16	-10000	0	-0.86	18	18
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.007	0.13	-10000	0	-0.67	18	18
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.031	0.061	-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	0.043	0.074	-10000	0	-10000	0	0
RABGGTA	0.013	0.047	-10000	0	-0.75	2	2
BCAR1	0.013	0.079	0.41	18	-0.58	1	19
RHOC	0.031	0.061	-10000	0	-10000	0	0
RHOA	0.031	0.061	-10000	0	-10000	0	0
cell motility	0.036	0.063	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.046	0.062	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.023	0.12	-10000	0	-0.67	18	18
ROCK1	0.036	0.064	-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	0.067	-10000	0	-10000	0	0
ATF5	0.011	0.067	-10000	0	-0.86	3	3

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	-0.006	0.086	0.78	6	-10000	0	6
PI3K Class IB/PDE3B	0.006	0.086	-10000	0	-0.78	6	6
PDE3B	0.006	0.086	-10000	0	-0.78	6	6

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.014	0.033	-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	0.12	-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	0.033	-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	78	78
CCM2	0.016	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.075	0.18	-10000	0	-0.5	78	78
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	78	78
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	0.017	0.05	-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	0.033	-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	-0.01	0.071	-10000	0	-0.5	10	10

×

ErbB2/ErbB3 signaling events

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
USP8	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.074	-10000	0	-0.72	3	3
NFATC4	0.047	0.077	-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	-0.017	0.077	-10000	0	-0.64	1	1
JUN	0.037	0.079	-10000	0	-0.41	2	2
HRAS	0.013	0.039	-10000	0	-0.87	1	1
DOCK7	0.02	0.091	-10000	0	-0.62	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.022	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	0.083	-10000	0	-0.72	1	1
RAF1	0.039	0.095	-10000	0	-0.68	3	3
ErbB2/ErbB3/neuregulin 2	-0.02	0.097	-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	-0.089	0.26	-10000	0	-0.6	9	9
FOS	-0.038	0.19	-10000	0	-0.48	15	15
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.077	-10000	0	-0.64	1	1
MAPK3	-0.058	0.21	-10000	0	-0.56	8	8
MAPK1	-0.058	0.21	-10000	0	-0.56	8	8
JAK2	0.02	0.088	-10000	0	-0.6	1	1
NF2	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.006	0.09	-10000	0	-0.82	2	2
NRG1	-0.014	0.13	-10000	0	-0.75	16	16
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.024	0.084	-10000	0	-0.44	2	2
MAPK9	-0.008	0.036	-10000	0	-10000	0	0
ERBB2	-0.002	0.036	-10000	0	-0.58	2	2
ERBB3	-0.004	0.099	-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	0.022	0.35	2	-10000	0	2
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	0.03	-10000	0	-0.49	2	2
CHRNA1	-0.13	0.28	-10000	0	-0.45	226	226
myelination	0.051	0.074	-10000	0	-0.49	2	2
PPP3CB	0.02	0.082	-10000	0	-0.55	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.014	0.069	-10000	0	-0.72	2	2
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
mol:GDP	0.007	0.089	-10000	0	-0.82	2	2
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.045	0.097	-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	0.02	0.087	-10000	0	-0.6	1	1
MAP2K1	-0.041	0.18	-10000	0	-0.57	8	8
heart morphogenesis	-0.017	0.077	-10000	0	-0.64	1	1
RAS family/GDP	-0.015	0.073	-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	0.021	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	-0.017	0.077	-10000	0	-0.64	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.065	0.089	0.32	33	-0.36	1	34
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	-0.069	0.25	-10000	0	-0.86	48	48
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	0.058	-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	0.067	0.093	0.33	33	-0.4	1	34
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	62	62
LNPEP	0.013	0.047	-10000	0	-0.75	2	2
YWHAE	0.016	0	-10000	0	-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	0.001	0.11	-10000	0	-0.77	10	10
EFNB1	0.018	0.096	-10000	0	-0.66	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.095	-10000	0	-0.74	3	3
Ephrin B2/EPHB1-2	-0.011	0.081	-10000	0	-0.54	11	11
neuron projection morphogenesis	-0.018	0.091	-10000	0	-0.71	3	3
Ephrin B1/EPHB1-2/Tiam1	-0.021	0.1	-10000	0	-0.81	3	3
DNM1	-0.001	0.12	-10000	0	-0.86	10	10
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.023	0.093	-10000	0	-0.67	9	9
YES1	-0.015	0.12	-10000	0	-0.9	9	9
Ephrin B1/EPHB1-2/NCK2	-0.02	0.099	-10000	0	-0.81	2	2
PI3K	-0.012	0.098	-10000	0	-0.69	10	10
mol:GDP	-0.02	0.1	-10000	0	-0.79	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	-0.012	0.094	-10000	0	-0.72	9	9
FGR	-0.016	0.12	-10000	0	-0.89	9	9
TIAM1	0.014	0.033	-10000	0	-0.75	1	1
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	0.018	0.14	-10000	0	-0.73	9	9
LYN	-0.015	0.12	-10000	0	-0.9	9	9
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	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	0.01	0.067	-10000	0	-0.75	4	4
EPHB1	0.011	0.061	-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	22	22
BLK	-0.022	0.12	-10000	0	-0.89	9	9
HCK	-0.021	0.12	-10000	0	-0.94	9	9
regulation of stress fiber formation	0.02	0.097	0.79	2	-10000	0	2
MAPK8	0.032	0.091	-10000	0	-0.63	9	9
Ephrin B1/EPHB1-2/RGS3	-0.02	0.099	-10000	0	-0.81	2	2
endothelial cell migration	-0.009	0.081	-10000	0	-0.61	9	9
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.01	0.11	-10000	0	-0.85	9	9
regulation of focal adhesion formation	0.02	0.097	0.79	2	-10000	0	2
chemotaxis	0.02	0.097	0.79	2	-10000	0	2
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
Rac1/GTP	-0.019	0.094	-10000	0	-0.74	3	3
angiogenesis	-0.016	0.1	-10000	0	-0.77	9	9
LCK	-0.02	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	0.013	0.051	-9999	-0.8	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.037	0.045	-9999	-0.48	4	4
MAPK12	0.028	0.085	-9999	-0.49	13	13
CCND1	0.013	0.071	-9999	-0.3	20	20
p38 gamma/SNTA1	0.033	0.089	-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	0.041	-9999	-0.47	3	3
MAPT	0.033	0.068	-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	0.07	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.011	0.073	-9999	-0.48	12	12
POMC	0.012	0.051	-9999	-0.8	2	2
EGFR	0.001	0.11	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.009	0.065	-9999	-0.47	10	10
AGRP	0.007	0.047	-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	-0.007	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	-0.47	35	35
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	-0.43	1	1
MC4R	-0.01	0.11	-9999	-0.86	9	9
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.75	19	19
FGFR/FGF/Syndecan-3	-0.001	0.019	-9999	-0.43	1	1
neuron projection morphogenesis	-0.022	0.089	-9999	-10000	0	0
Syndecan-3/AgRP	-0.002	0.03	-9999	-0.4	3	3
Syndecan-3/AgRP/MC4R	-0.01	0.067	-9999	-0.47	9	9
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	-0.46	35	35
IL8	-0.04	0.21	-9999	-0.84	34	34
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	-0.014	0.095	-9999	-0.66	11	11
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	0.094	-9999	-0.75	8	8
Rac1/GDP	0.068	0.076	-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	0.046	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.036	-9999	-0.22	6	6
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.084	-9999	-10000	0	0
RAPGEF1	0.054	0.099	-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	0.043	0.11	-9999	-0.49	1	1
E-cadherin/gamma catenin/alpha catenin	-0.022	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	-0.007	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	0.044	-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	0.033	-9999	-0.75	1	1
E-cadherin(dimer)/Ca2+	-0.016	0.08	-9999	-10000	0	0
AKT1	-0.005	0.025	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
CDH1	-0.016	0.15	-9999	-0.75	21	21
RhoA/GDP	0.067	0.075	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.034	-9999	-0.24	2	2
CDC42/GDP	0.067	0.075	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.068	-9999	-0.32	23	23
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.017	0.084	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.082	-9999	-0.41	21	21
mol:GDP	0.063	0.086	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.058	-9999	-0.75	3	3
p120 catenin/RhoA/GDP	-0.012	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	0.035	0.064	-9999	-0.26	20	20
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	-0.008	0.041	-9999	-10000	0	0
WASF2	-0.005	0.018	-9999	-10000	0	0
Rap1/GTP	-0.011	0.054	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.087	-9999	-0.81	1	1
CCND1	-0.016	0.065	-9999	-0.33	20	20
VAV2	0.049	0.1	-9999	-0.5	1	1
RAP1/GDP	-0.011	0.056	-9999	-10000	0	0
adherens junction assembly	0.033	0.11	-9999	-0.49	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	-0.017	0.081	-9999	-0.77	1	1
E-cadherin/beta catenin	-0.018	0.09	-9999	-0.45	21	21
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.021	0.1	-9999	-0.51	21	21
PIK3CA	0.014	0.033	-9999	-0.75	1	1
Rac1/GTP	-0.02	0.072	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.019	0.094	-9999	-0.48	21	21
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.022	0.11	-9999	-0.55	21	21

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.003	0.12	-9999	-0.82	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	0.045	0	-9999	-10000	0	0
TSHR	-0.045	0.2	-9999	-0.59	59	59
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	0.021	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.028	0.055	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	-0.05	0.23	-9999	-0.86	39	39
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	0.03	-9999	-10000	0	0
positive regulation of phagocytosis	0.025	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.044	0.16	-9999	-0.59	39	39
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	-0.015	0.11	-9999	-10000	0	0
VAMP3	0.025	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.06	-9999	-0.4	11	11
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	-0.006	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	0.026	-9999	-10000	0	0
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	-0.12	0.21	-9999	-0.37	215	215
RALA	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.025	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	33	33
HRAS	0.014	0.039	-9999	-0.86	1	1
PRKCB	0.009	0.083	-9999	-0.83	5	5
NRAS	0.016	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.023	-9999	-0.53	1	1
MAPK3	0.029	0.085	-9999	-0.52	3	3
MAP2K1	0.055	0.056	-9999	-0.48	5	5
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.004	0.044	-9999	-0.44	5	5
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	-0.44	5	5
KRAS	0.016	0.001	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.006	0.065	-9999	-0.67	5	5
CRKL	0.04	0.065	-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	0.062	-9999	-0.43	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.75	1	1
HGF/MET/SHIP2	-0.029	0.13	-9999	-0.57	26	26
MAP3K5	-0.024	0.12	-9999	-0.41	1	1
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.027	0.12	-9999	-0.61	15	15
AP1	-0.014	0.082	-9999	-0.52	13	13
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.039	-9999	-0.86	1	1
apoptosis	0.004	0.11	-9999	-0.7	12	12
STAT3 (dimer)	0.041	0.078	-9999	-0.53	3	3
GAB1/CRKL/SHP2/PI3K	-0.011	0.055	-9999	-0.59	2	2
INPP5D	0.009	0.077	-9999	-0.86	4	4
CBL/CRK	0.047	0.068	-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	0.001	0.03	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.039	-9999	-0.34	2	2
PAK1	0.01	0.019	-9999	-0.42	1	1
HGF/MET/RANBP10	-0.029	0.13	-9999	-0.57	26	26
HRAS	0.031	0.098	-9999	-0.71	3	3
DOCK1	0.048	0.069	-9999	-0.51	3	3
GAB1	0.031	0.068	-9999	-0.44	3	3
CRK	0.04	0.065	-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	0.06	-9999	-0.4	5	5
PIK3R1	0.014	0.033	-9999	-0.75	1	1
cell morphogenesis	0.079	0.085	-9999	-0.65	2	2
GRB2/SHC	-0.012	0.057	-9999	-0.54	3	3
FOS	-0.004	0.12	-9999	-0.76	13	13
GLMN	0	0	-9999	-10000	0	0
cell motility	0.001	0.03	-9999	-0.29	5	5
HGF/MET/MUC20	-0.029	0.13	-9999	-0.58	26	26
cell migration	-0.011	0.056	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.75	1	1
MET/RANBP10	-0.006	0.065	-9999	-0.67	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.016	0.072	-9999	-0.58	3	3
MET/MUC20	-0.007	0.066	-9999	-0.68	5	5
RAP1B	0.058	0.059	-9999	-10000	0	0
RAP1A	0.058	0.059	-9999	-10000	0	0
HGF/MET/RANBP9	-0.029	0.13	-9999	-0.57	26	26
RAF1	0.041	0.093	-9999	-0.66	3	3
STAT3	-0.015	0.066	-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	0.012	0.097	-9999	-0.56	1	1
SRC	0.042	0.079	-9999	-0.55	3	3
PI3K	-0.012	0.061	-9999	-0.54	4	4
MET/Glomulin	0.009	0.061	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.05	0.088	-9999	-0.6	3	3
MET	0.007	0.086	-9999	-0.86	5	5
MAP4K1	-0.037	0.12	-9999	-0.4	12	12
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.049	0.089	-9999	-0.6	3	3
BAD	0.008	0.045	-9999	-0.67	2	2
MAP2K4	-0.012	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.056	-9999	-0.57	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	0.033	-9999	-0.75	1	1
NCK1	0.014	0.033	-9999	-0.75	1	1
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.013	0.059	-9999	-0.53	3	3
PDPK1	-0.014	0.021	-9999	-0.49	1	1
HGF/MET/SHIP	-0.033	0.14	-9999	-0.59	29	29

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.02	0.17	-10000	0	-0.72	26	26
regulation of axonogenesis	-0.033	0.034	-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	0.03	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.073	-10000	0	-0.33	26	26
MAPK3	0.024	0.068	-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	0.07	-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	0.068	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.012	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.025	-10000	0	-0.56	1	1
RhoA/GDP	-0.014	0.062	-10000	0	-10000	0	0
NME1	0.017	0.004	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.062	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.016	0.073	-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	0.07	-10000	0	-0.32	26	26
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.029	-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	0.033	-10000	0	-0.75	1	1
tube morphogenesis	-0.016	0.073	-10000	0	-0.33	26	26
ruffle organization	0.033	0.034	-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	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.03	-10000	0	-10000	0	0
Rac1/GTP	-0.017	0.073	-10000	0	-0.33	26	26

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.002	0.012	-9999	-10000	0	0
DOCK1	0.014	0.033	-9999	-0.75	1	1
ITGA4	-0.01	0.15	-9999	-0.86	15	15
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.019	0.11	-9999	-0.67	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.017	0.097	-9999	-0.58	15	15
alpha4/beta7 Integrin/Paxillin	-0.015	0.088	-9999	-0.52	15	15
lamellipodium assembly	-0.001	0.043	-9999	-0.77	1	1
PIK3CA	0.014	0.033	-9999	-0.75	1	1
PI3K	-0.002	0.035	-9999	-0.56	2	2
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.031	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
ARF6/GTP	-0.013	0.074	-9999	-10000	0	0
cell adhesion	-0.014	0.081	-9999	-0.48	15	15
CRKL/CBL	-0.001	0.025	-9999	-0.56	1	1
alpha4/beta1 Integrin/Paxillin	-0.015	0.088	-9999	-0.52	15	15
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ARF6/GDP	0.002	0.012	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.026	0.11	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.002	0.029	-9999	-0.48	2	2
VCAM1	-0.007	0.14	-9999	-0.82	14	14
alpha4/beta1 Integrin/Paxillin/Talin	-0.014	0.082	-9999	-0.49	15	15
alpha4/beta1 Integrin/Paxillin/GIT1	-0.014	0.082	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.75	1	1
mol:GDP	0.014	0.081	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.75	1	1
PRKACA	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.014	0.082	-9999	-0.49	15	15
Rac1/GTP	-0.001	0.051	-9999	-0.93	1	1

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.056	0.16	-10000	0	-0.5	59	59
cell-cell adhesion	0.013	0.073	0.63	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	-0.015	0.08	-10000	0	-0.59	3	3
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
SHC1	0.014	0.039	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.013	0.08	-10000	0	-0.49	14	14
Ephrin B1/EPHB1	-0.003	0.04	-10000	0	-0.52	3	3
HRAS/GDP	-0.008	0.053	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.014	0.073	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.035	0.086	-10000	0	-0.75	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.009	0.058	-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	0.088	-10000	0	-0.75	7	7
PAK1	0.047	0.084	-10000	0	-0.76	1	1
HRAS	0.014	0.039	-10000	0	-0.86	1	1
RRAS	0.036	0.087	-10000	0	-0.54	4	4
DNM1	-0.001	0.12	-10000	0	-0.86	10	10
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.043	0.063	-10000	0	-10000	0	0
lamellipodium assembly	-0.013	0.073	-10000	0	-0.63	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.006	0.037	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
EPHB2	0.001	0.11	-10000	0	-0.77	10	10
EPHB3	-0.005	0.12	-10000	0	-0.75	14	14
EPHB1	0.011	0.061	-10000	0	-0.78	3	3
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.06	-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	0.083	-10000	0	-0.78	2	2
Ephrin B/EPHB1	-0.009	0.06	-10000	0	-0.5	1	1
RAP1/GDP	-0.003	0.052	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.004	0.094	-10000	0	-0.75	8	8
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.011	0.081	-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	59	59
MAPK3	0.065	0.041	-10000	0	-10000	0	0
MAPK1	0.065	0.041	-10000	0	-10000	0	0
Rac1/GDP	-0.003	0.055	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.011	0.058	-10000	0	-0.49	2	2
CDC42/GDP	-0.003	0.055	-10000	0	-10000	0	0
PI3K	-0.002	0.025	-10000	0	-10000	0	0
EFNA5	-0.057	0.22	-10000	0	-0.75	49	49
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.01	0.056	-10000	0	-0.6	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	0.042	0.084	-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	-0.49	3	3
MAP2K1	0.057	0.043	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.012	0.082	-10000	0	-0.66	5	5
cell migration	0.067	0.049	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.035	0.088	-10000	0	-0.77	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.074	0.23	-10000	0	-0.79	3	3
HRAS/GTP	-0.016	0.085	-10000	0	-0.72	4	4
Ephrin B1/EPHB1-2	-0.011	0.081	-10000	0	-0.54	11	11
cell adhesion mediated by integrin	0.01	0.065	0.46	8	-10000	0	8
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	-0.77	5	5
RASA1	0.014	0.033	-10000	0	-0.75	1	1
RAC1-CDC42/GDP	-0.003	0.052	-10000	0	-10000	0	0
ruffle organization	0.07	0.088	-10000	0	-0.64	3	3
NCK1	0.014	0.033	-10000	0	-0.75	1	1
receptor internalization	0.036	0.11	-10000	0	-0.72	1	1
Ephrin B/EPHB2/KALRN	-0.014	0.079	-10000	0	-0.59	3	3
ROCK1	0.021	0.077	-10000	0	-0.44	14	14
RAS family/GDP	-0.011	0.058	-10000	0	-0.53	1	1
Rac1/GTP	-0.014	0.078	-10000	0	-0.69	3	3
Ephrin B/EPHB1/Src/Paxillin	-0.006	0.042	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.01	0.066	-10000	0	-0.5	6	6
ER alpha/Gai/GDP/Gbeta gamma	0.054	0.055	-10000	0	-10000	0	0
AKT1	0.046	0.073	-10000	0	-0.65	5	5
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.041	0.073	-10000	0	-0.73	4	4
mol:Ca2+	-0.015	0.19	-10000	0	-0.68	12	12
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.008	0.069	-10000	0	-0.56	7	7
SHC1	0.014	0.039	-10000	0	-0.86	1	1
apoptosis	-0.046	0.07	0.62	5	-10000	0	5
RhoA/GTP	-0.004	0.037	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.007	0.045	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.067	0.047	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	0.041	-10000	0	-0.47	4	4
pseudopodium formation	0.067	0.047	-10000	0	-0.54	1	1
E2/ER alpha (dimer)/PELP1	-0.004	0.045	-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	0.084	-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	0.061	-10000	0	-0.46	4	4
E2/ER beta (dimer)	-0.009	0.075	-10000	0	-0.65	7	7
mol:GDP	-0.009	0.06	-10000	0	-0.47	4	4
mol:NADP	0.063	0.061	-10000	0	-0.46	4	4
PIK3R1	0.014	0.033	-10000	0	-0.75	1	1
mol:IP3	-0.017	0.19	-10000	0	-0.72	12	12
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.023	0.098	-10000	0	-0.58	9	9
PLCB2	-0.068	0.17	-10000	0	-0.49	64	64
IGF1	0.006	0.094	-10000	0	-0.86	6	6
mol:L-citrulline	0.063	0.061	-10000	0	-0.46	4	4
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	-0.65	7	7
BCAR1	0.014	0.033	-10000	0	-0.75	1	1
ESR2	0.004	0.098	-10000	0	-0.83	7	7
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.01	0.069	-10000	0	-0.78	4	4
Gq family/GDP/Gbeta gamma	-0.016	0.074	-10000	0	-0.56	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.052	0.032	-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	0.058	-10000	0	-0.75	3	3
E2/ER alpha (dimer)	-0.005	0.053	-10000	0	-0.6	4	4
STRN	0.01	0.067	-10000	0	-0.75	4	4
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.016	0.072	-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	0.058	-10000	0	-0.75	3	3
HBEGF	-0.042	0.14	-10000	0	-0.5	7	7
cAMP biosynthetic process	-0.009	0.064	-10000	0	-0.44	11	11
SRC	0.063	0.052	-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	0.052	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.009	0.05	-10000	0	-10000	0	0
Gs family/GTP	-0.009	0.065	-10000	0	-0.45	11	11
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.023	-10000	0	-0.53	1	1
vasodilation	0.063	0.059	-10000	0	-0.44	4	4
mol:DAG	-0.017	0.19	-10000	0	-0.72	12	12
Gs family/GDP/Gbeta gamma	-0.007	0.047	-10000	0	-10000	0	0
MSN	0.069	0.051	-10000	0	-0.6	1	1
Gq family/GTP	-0.019	0.078	-10000	0	-0.46	10	10
mol:PI-3-4-5-P3	0.042	0.07	-10000	0	-0.7	4	4
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.063	0.059	0.44	4	-10000	0	4
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.008	0.056	-10000	0	-0.45	3	3
NOS3	0.064	0.063	-10000	0	-0.48	4	4
GNA11	0.011	0.058	-10000	0	-0.75	3	3
MAPKKK cascade	0.072	0.071	-10000	0	-0.59	4	4
E2/ER alpha (dimer)/PELP1/Src	-0.007	0.046	-10000	0	-0.48	3	3
ruffle organization	0.067	0.047	-10000	0	-0.54	1	1
ROCK2	-0.005	0.048	-10000	0	-0.68	1	1
GNA14	0.005	0.088	-10000	0	-0.75	7	7
GNA15	-0.01	0.15	-10000	0	-0.86	15	15
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.17	0.25	-10000	0	-0.66	8	8
MMP2	0.066	0.08	-10000	0	-0.66	3	3

×

BARD1 signaling events

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
BARD1/CSTF1	-0.004	0.049	-10000	0	-0.56	4	4
ATM	0.014	0.033	-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	0.072	-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	-0.52	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	0.077	-10000	0	-0.67	7	7
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.049	-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	109	109
DNA repair	0.043	0.14	-10000	0	-0.67	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.049	-10000	0	-0.56	4	4
BARD1/DNA-PK	-0.003	0.037	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.049	0.56	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	-0.004	0.042	-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	0.037	-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	0.067	-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	-0.017	0.092	-10000	0	-0.52	14	14
BARD1/DNA-PK/P53	-0.003	0.034	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.049	-10000	0	-0.56	4	4
BRCA1/BARD1/CTIP	-0.005	0.053	-10000	0	-0.86	1	1
FA complex	-0.057	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.049	-10000	0	-0.56	4	4
RBBP8	0.029	0.046	-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	0.037	-10000	0	-10000	0	0
BRCA1/BARD1	-0.01	0.073	-10000	0	-0.9	1	1
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.05	-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	-0.008	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	0.049	-10000	0	-0.56	4	4
EWSR1	0.016	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.014	0.033	-10000	0	-0.75	1	1
ANTXR2	0.014	0.033	-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	0.085	-10000	0	-0.37	21	21
MAP2K2	-0.002	0.035	-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	0.033	-10000	0	-0.43	3	3
CYAA	0.02	0.027	-10000	0	-0.42	2	2
MAP2K4	0	0.005	-10000	0	-10000	0	0
IL1B	0.017	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	0.081	-10000	0	-0.44	18	18
PA/Cellular Receptors	-0.002	0.03	-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	0.081	-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	-0.52	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	0.023	-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	0.026	-10000	0	-0.42	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.057	0.052	-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	-0.013	0.06	-10000	0	-10000	0	0
FMN1	0.023	0.12	-10000	0	-0.39	28	28
mol:IP3	-0.008	0.04	-10000	0	-0.48	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.065	-10000	0	-0.71	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.054	0.057	-10000	0	-0.51	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	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	0.074	-10000	0	-0.56	2	2
VASP	0.045	0.072	-10000	0	-0.66	1	1
ZYX	0.045	0.072	-10000	0	-0.66	1	1
JUB	0.042	0.08	-10000	0	-0.58	2	2
EGFR(dimer)	-0.02	0.082	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.021	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	0.033	-10000	0	-0.74	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	0.039	-10000	0	-0.47	1	1
JUP	-0.003	0.057	-10000	0	-0.74	3	3
PIK3R1	0.015	0.033	-10000	0	-0.74	1	1
mol:DAG	-0.008	0.04	-10000	0	-0.48	1	1
CDH1	-0.03	0.15	-10000	0	-0.74	21	21
RhoA/GDP	-0.013	0.06	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.045	0.071	-10000	0	-0.64	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	0.001	0.11	-10000	0	-0.85	9	9
CASR	-0.29	0.15	-10000	0	-0.54	18	18
RhoA/GTP	-0.007	0.035	-10000	0	-10000	0	0
AKT2	0.054	0.057	-10000	0	-0.51	1	1
actin cable formation	0.033	0.12	-10000	0	-0.64	2	2
apoptosis	0.009	0.043	0.49	1	-10000	0	1
CTNNA1	0.016	0.004	-10000	0	-10000	0	0
mol:GDP	-0.015	0.066	-10000	0	-0.49	1	1
PIP5K1A	0.044	0.076	-10000	0	-0.58	2	2
PLCG1	-0.008	0.041	-10000	0	-0.49	1	1
Rac1/GTP	-0.018	0.074	-10000	0	-0.6	1	1
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.01	0.061	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.057	-9999	-0.68	1	1
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.048	-9999	-0.55	4	4
AP1	-0.018	0.088	-9999	-0.7	5	5
ILK	0.062	0.06	-9999	-10000	0	0
bone resorption	-0.025	0.1	-9999	-0.74	3	3
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.007	0.05	-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	-0.65	24	24
alphaV/beta3 Integrin/Osteopontin	-0.007	0.056	-9999	-0.49	2	2
MAP3K1	0.062	0.06	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.074	0.078	-9999	-10000	0	0
MAPK1	0.074	0.078	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.75	1	1
MAPK8	0.074	0.067	-9999	-0.78	1	1
ITGB3	0.016	0.067	-9999	-0.74	4	4
NFKBIA	0.087	0.078	-9999	-10000	0	0
FOS	-0.003	0.12	-9999	-0.76	13	13
CD44	-0.02	0.17	-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	0.059	-9999	-0.64	1	1
BCAR1	0.014	0.033	-9999	-0.75	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.004	0.048	-9999	-0.55	4	4
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.058	0.066	-9999	-10000	0	0
VAV3	0.057	0.099	-9999	-0.78	1	1
MAP3K14	0.06	0.079	-9999	-0.5	4	4
ROCK2	0.011	0.058	-9999	-0.75	3	3
SPP1	0.016	0.067	-9999	-0.74	4	4
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.016	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 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
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.016	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.021	-9999	-10000	0	0
forebrain development	0.055	0.095	-9999	-0.5	2	2
GNAO1	0.008	0.084	-9999	-0.84	5	5
SMO/beta Arrestin2	-0.002	0.038	-9999	-0.61	2	2
SMO	0.016	0.034	-9999	-0.74	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	-0.018	0.096	-9999	-0.52	18	18
GNAI1	0.011	0.058	-9999	-0.74	3	3
XPO1	0.019	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.014	0.062	-9999	-10000	0	0
SAP30	-0.015	0.16	-9999	-0.86	18	18
mol:GDP	0.016	0.034	-9999	-0.74	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.033	-9999	-0.75	1	1
GNAI3	0.016	0.004	-9999	-10000	0	0
GLI2	0.058	0.031	-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	0.033	-9999	-0.74	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.044	0.052	-9999	-0.55	1	1
SIN3B	0.016	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.058	0.044	-9999	-10000	0	0
GLI2/Su(fu)	0.075	0.037	-9999	-10000	0	0
FOXA2	-0.062	0.22	-9999	-0.83	38	38
neural tube patterning	0.055	0.095	-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	0.033	-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	0.055	0.095	-9999	-0.5	2	2
SUFU	0.038	0.021	-9999	-10000	0	0
LGALS3	-0.005	0.13	-9999	-0.86	12	12
catabolic process	0.093	0.031	-9999	-10000	0	0
GLI3A/CBP	0.017	0.057	-9999	-10000	0	0
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.055	0.096	-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	0.016	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.013	0.082	-9999	-0.54	12	12
GNAZ	0.011	0.058	-9999	-0.75	3	3
RBBP4	0.014	0.033	-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	0.061	0.029	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.052	0.047	-9999	-0.48	1	1
PTCH1	0.062	0.1	-9999	-1.1	1	1
MIM/GLI1	0.051	0.15	-9999	-0.72	1	1
CREBBP	0.017	0.057	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.057	0.047	-9999	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	0.027	0.1	-9999	-10000	0	0
BAG4	0.014	0.033	-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	80	80
BAX	0.032	0.036	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.027	-9999	-10000	0	0
IKBKB	0.037	0.097	-9999	-10000	0	0
MAP2K2	0.046	0.053	-9999	-0.38	4	4
MAP2K1	0.047	0.05	-9999	-10000	0	0
SMPD1	0.019	0.028	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.038	0.098	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.039	0.098	-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	-10000	0	0
RAF1	0.039	0.053	-9999	-0.42	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	0.05	-9999	-0.37	4	4
MAPK1	0.05	0.05	-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	0.055	-9999	-0.45	4	4
MAPK8	0.049	0.037	-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	0.097	-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	0.097	-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	0.068	-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	-10000	0	0
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.073	-9999	-0.73	5	5
VDR	0.011	0.058	-9999	-0.75	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.077	0.05	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.087	0.062	-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	-0.02	0.073	-9999	-10000	0	0
RXRs/NUR77	-0.008	0.088	-9999	-0.5	5	5
RXRs/PPAR	0.058	0.03	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.043	-9999	-0.57	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.039	-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	-0.74	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	-0.02	0.073	-9999	-10000	0	0
THRA	0.014	0.033	-9999	-0.75	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.043	-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	-0.75	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.068	-9999	-0.41	2	2
RXRG	0.015	0.077	-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	32	32
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	0.087	0.062	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.013	0.047	-9999	-0.75	2	2
RXRs/NUR77/BCL2	-0.01	0.055	-9999	-10000	0	0
SREBF1	0.093	0.065	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.057	-9999	-0.5	4	4
ABCA1	0.092	0.072	-9999	-0.66	2	2
RARs/THRs	-0.027	0.099	-9999	-10000	0	0
RXRs/FXR	-0.009	0.093	-9999	-0.5	7	7
BCL2	0.016	0	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.076	0.027	-10000	0	-10000	0	0
NFATC2	0.054	0.033	-10000	0	-0.32	1	1
NFATC3	0.029	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	0.013	0.051	-10000	0	-0.8	2	2
CABIN1/MEF2D	0.037	0.068	-10000	0	-0.45	3	3
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.033	-10000	0	-0.75	1	1
activation-induced cell death of T cells	-0.037	0.067	0.44	3	-10000	0	3
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	62	62
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	0.047	-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	0.015	0.034	-10000	0	-0.75	1	1
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	0.024	-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	-0.4	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.077	-10000	0	-0.47	2	2
PRKCB	0.008	0.082	-10000	0	-0.82	5	5
PRKCE	0.014	0.033	-10000	0	-0.75	1	1
JNK2/NFAT4	-0.003	0.033	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.002	0.038	-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	0.058	-10000	0	-0.75	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.031	0.18	-10000	0	-0.86	23	23
PRKCQ	-0.006	0.13	-10000	0	-0.75	15	15
FKBP38/BCL2	-0.001	0.025	-10000	0	-0.56	1	1
EP300	0.015	0.033	-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	0.034	-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	0.03	-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	0.054	-10000	0	-0.52	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	0.029	0.04	-10000	0	-0.49	3	3
NFAT1/CK1 alpha	-0.003	0.017	-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	0.047	-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	0.081	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

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.011	0.058	-10000	0	-0.75	3	3
Cbp/p300/PCAF	-0.002	0.04	-10000	0	-0.92	1	1
EP300	0.014	0.033	-10000	0	-0.75	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.056	0.034	-10000	0	-0.43	1	1
KAT2B	0.014	0.033	-10000	0	-0.75	1	1
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.03	0.038	0.24	1	-0.3	2	3
RAR alpha/9cRA/Cyclin H	-0.009	0.038	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.052	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	-0.01	0.047	-10000	0	-0.59	1	1
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.043	-10000	0	-0.57	3	3
RXRs/RARs/NRIP1/9cRA	0.063	0.083	-10000	0	-0.52	1	1
NCOA2	0.003	0.1	-10000	0	-0.75	9	9
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	-0.74	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	0.016	0.033	-10000	0	-0.74	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.018	0.074	-10000	0	-10000	0	0
RARA	0.025	0.059	-10000	0	-0.28	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.047	0.063	-10000	0	-0.61	2	2
PRKCA	0.021	0.001	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.054	0.084	-10000	0	-0.57	1	1
RXRG	0.012	0.092	-10000	0	-0.38	27	27
RXRA	0.036	0.056	-10000	0	-10000	0	0
RXRB	0.017	0.085	-10000	0	-0.37	23	23
VDR/Vit D3/DNA	-0.003	0.043	-10000	0	-0.57	3	3
RBP1	0.009	0.075	-10000	0	-0.84	4	4
CRBP1/9-cic-RA	-0.005	0.057	-10000	0	-0.65	4	4
RARB	0.016	0.047	-10000	0	-0.75	2	2
PRKCG	-0.026	0.18	-10000	0	-0.86	23	23
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.053	0.084	-10000	0	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.061	0.075	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.047	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.054	0.084	-10000	0	-0.57	1	1
positive regulation of DNA binding	-0.008	0.036	-10000	0	-10000	0	0
NRIP1	0.053	0.092	-10000	0	-1.2	1	1
RXRs/RARs	0.046	0.082	-10000	0	-0.41	1	1
RXRs/RXRs/DNA/9cRA	-0.017	0.074	-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	-0.006	0.026	-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

×

Regulation of p38-alpha and p38-beta

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
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	0.058	-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	0.033	-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	-0.003	0.12	-9999	-0.75	13	13
DUSP8	0.014	0.033	-9999	-0.75	1	1
PGK/cGMP/p38 alpha	-0.019	0.063	-9999	-0.44	3	3
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	0.084	-9999	-0.42	2	2
BLK	-0.041	0.22	-9999	-0.86	33	33
HCK	-0.032	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	0.057	0.066	-9999	-0.34	2	2
positive regulation of innate immune response	0.068	0.091	-9999	-0.44	2	2
LCK	-0.021	0.18	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.073	0.088	-9999	-10000	0	0
p38alpha-beta/MKP5	0.071	0.093	-9999	-10000	0	0
PGK/cGMP	-0.014	0.089	-9999	-0.57	13	13
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.072	0.089	-9999	-10000	0	0
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

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.062	-9999	-10000	0	0
TC10/GTP	-0.006	0.052	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.039	-9999	-10000	0	0
HRAS	0.014	0.039	-9999	-0.86	1	1
APS homodimer	0.006	0.094	-9999	-0.86	6	6
GRB14	-0.025	0.17	-9999	-0.75	28	28
FOXO3	-0.003	0.013	-9999	-10000	0	0
AKT1	-0.022	0.085	-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	0.033	-9999	-0.75	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.006	0.15	-9999	-0.51	37	37
CBL/APS/CAP/Crk-II/C3G	-0.007	0.057	-9999	-0.49	6	6
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.039	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.041	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.024	-9999	-10000	0	0
RPS6KB1	0.055	0.096	-9999	-0.58	2	2
PARD6A	0.011	0.058	-9999	-0.75	3	3
CBL	0.014	0.033	-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	0.033	-9999	-0.75	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.019	0.074	-9999	-0.59	2	2
HRAS/GTP	-0.007	0.056	-9999	-0.73	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.004	0.042	-9999	-0.5	1	1
PRKCI	-0.005	0.019	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.024	0.093	-9999	-0.73	2	2
SHC1	0.014	0.039	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	-0.001	0.036	-9999	-0.82	1	1
PI3K	-0.005	0.042	-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	0.085	-9999	-0.66	2	2
PRKCZ	-0.009	0.056	-9999	-0.7	3	3
SH2B2	0.006	0.094	-9999	-0.86	6	6
SHC/SHIP	-0.008	0.063	-9999	-0.55	5	5
F2RL2	-0.034	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	0.033	-9999	-0.75	1	1
NCK1	0.014	0.033	-9999	-0.75	1	1
CBL/APS/CAP/Crk-II	-0.008	0.062	-9999	-0.52	6	6
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.024	-9999	-0.54	1	1
INPP5D	0.029	0.068	-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	0.01	0.067	-9999	-0.75	4	4
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	0.029	0.067	-9999	-0.6	4	4
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.032	0.15	-9999	-0.73	6	6
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.75	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.014	0.033	-9999	-0.75	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.003	0.028	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.04	-9999	-0.46	4	4
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.03	0.12	-9999	-0.5	29	29

×

PDGFR-beta signaling 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
S1P1/Sphingosine-1-phosphate	-0.036	0.12	-9999	-0.46	18	18
PDGFB-D/PDGFRB/SLAP	-0.031	0.14	-9999	-0.67	24	24
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.065	-9999	-0.56	7	7
AKT1	-0.002	0.022	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.013	0.14	-9999	-0.48	18	18
PIK3CA	0.014	0.033	-9999	-0.75	1	1
FGR	-0.004	0.029	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.043	0.13	-9999	-0.57	19	19
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	0.088	-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	-0.031	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	0.076	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.036	0.082	-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	-0.038	0.12	-9999	-0.51	10	10
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-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	0.065	-9999	-0.57	7	7
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.087	-9999	-0.46	1	1
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.75	1	1
VAV2	0.035	0.088	-9999	-10000	0	0
CBL	0.014	0.033	-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	0.033	0.06	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.033	0.071	-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	-0.52	19	19
SLA	-0.025	0.18	-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	0.061	-9999	-0.49	8	8
SH2B2	0.006	0.094	-9999	-0.86	6	6
PLCgamma1/SPHK1	0.012	0.14	-9999	-0.49	18	18
LYN	-0.001	0.014	-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	0.023	-9999	-10000	0	0
SPHK1	-0.057	0.24	-9999	-0.86	43	43
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.038	0.041	-9999	-10000	0	0
PLCG1	0.039	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.021	-9999	-0.48	1	1
YES1	-0.001	0.014	-9999	-10000	0	0
cell migration	-0.001	0.021	-9999	-0.48	1	1
SHC/Grb2/SOS1	-0.001	0.02	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-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	0.045	0.1	-9999	-0.5	2	2
PRKCD	0.042	0.028	-9999	-0.53	1	1
FER	0.041	0.033	-9999	-10000	0	0
MAPKKK cascade	0	0.022	-9999	-10000	0	0
RASA1	0.042	0.025	-9999	-10000	0	0
NCK1	0.014	0.033	-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 S117. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.67	20	20
GATA1/HDAC5	-0.027	0.13	-10000	0	-0.66	21	21
GATA2/HDAC5	-0.014	0.088	-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	-0.58	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	-0.67	1	1
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.014	0.033	-10000	0	-0.75	1	1
HDAC5	0.014	0.033	-10000	0	-0.75	1	1
GNB1/GNG2	0	0	-10000	0	-10000	0	0
Histones	-0.003	0.04	-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	0.038	-10000	0	-0.61	2	2
CAMK4	0.013	0.047	-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	0.029	-10000	0	-0.48	2	2
HDAC4/ER alpha	-0.005	0.051	-10000	0	-0.59	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.051	0.043	-10000	0	-0.82	1	1
cell motility	-0.001	0.021	-10000	0	-0.47	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	0.01	0.069	-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	0.033	-10000	0	-0.75	1	1
HDAC11	0.013	0.047	-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	0.017	0.39	1	-10000	0	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.016	-10000	0	-10000	0	0
CLOCK	0.019	0.033	-10000	0	-0.74	1	1
TIMELESS/CRY2	0.056	0.025	-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	0.053	0.07	-10000	0	-1	2	2
ARNTL	0.02	0.003	-10000	0	-10000	0	0
TIMELESS	0.056	0.028	-10000	0	-10000	0	0
NPAS2	0.006	0.1	-10000	0	-0.74	10	10
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.009	0.12	2	-10000	0	2
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.009	-10000	0	-0.12	2	2
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.044	0.075	-10000	0	-0.46	11	11
BMAL1/CLOCK	0.064	0.056	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.016	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.002	0.016	-10000	0	-10000	0	0
mol:NADPH	0.019	0.009	-10000	0	-0.12	2	2
PER1/TIMELESS	0.056	0.025	-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 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.004	0.037	-10000	0	-0.4	2	2
FRAP1	0.02	0.013	-10000	0	-10000	0	0
AKT1	-0.004	0.037	-10000	0	-0.47	2	2
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.029	-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	0.036	-10000	0	-0.39	4	4
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	0.033	-10000	0	-0.75	1	1
apoptosis	0.014	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	4	4
EIF4B	0.044	0.022	-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	0.039	-10000	0	-0.36	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.042	0.018	-10000	0	-10000	0	0
FKBP1A	0.016	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.025	-10000	0	-0.41	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	4	4
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.004	0.044	-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	0.031	-10000	0	-0.5	1	1
tumor necrosis factor receptor activity	0	0	0.002	4	-10000	0	4
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	0.008	0.038	-10000	0	-0.42	4	4
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.004	0.034	-10000	0	-0.37	2	2
EIF4EBP1	-0.008	0.1	-10000	0	-0.46	25	25
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	0.002	0.091	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.049	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	0.013	0.051	-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	-0.53	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	0.033	-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	-0.34	1	1
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.041	0.052	-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	0.058	0.007	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.021	-9999	-0.48	1	1
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.03	-9999	-0.45	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.002	-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	0.033	-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	-0.48	1	1
TSC1/TSC2	0.059	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.02	-9999	-0.46	1	1
glucose import	0.03	0.08	-9999	-0.48	12	12
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0.005	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.03	0.081	-9999	-0.48	12	12
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	62	62
G1/S transition of mitotic cell cycle	0.06	0.007	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	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

×

Signaling events mediated by HDAC Class I

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
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	0.048	-9999	-0.54	1	1
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.058	-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	-0.72	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	0.04	-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	0.042	-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	-0.008	0.045	-9999	-0.53	2	2
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.014	0.033	-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	0.033	-9999	-0.75	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.007	0.038	-9999	-10000	0	0
SIN3 complex	-0.018	0.096	-9999	-0.52	18	18
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.015	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	0.036	-9999	-0.64	1	1
YY1/HDAC2	-0.001	0.032	-9999	-0.72	1	1
YY1/HDAC1	-0.001	0.032	-9999	-0.72	1	1
NuRD/MBD2 Complex (MeCP1)	0.064	0.01	-9999	-10000	0	0
PPARG	-0.006	0.047	-9999	-10000	0	0
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	0.024	-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	0.037	-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	0.033	-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	0.097	-9999	-0.52	19	19
EP300	0.014	0.033	-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	0.064	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.026	-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	-0.013	0.069	-9999	-0.42	12	12
GATA1/HDAC1	-0.026	0.13	-9999	-0.67	20	20
GATA1/HDAC3	-0.023	0.1	-9999	-0.52	20	20
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.009	0.076	-9999	-0.61	8	8
SIN3/HDAC complex/Mad/Max	0.056	0.04	-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	-0.029	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	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.045	-9999	-10000	0	0
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	0.013	0.051	-9999	-0.8	2	2
MBD2	0.016	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	-0.003	0.041	-9999	-0.67	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	-0.008	0.038	-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	0.058	-9999	-0.75	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.003	0.041	-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	0.033	-9999	-0.75	1	1
NF kappa B1 p50 dimer	0.025	0.026	-9999	-0.56	1	1
PIK3R1	0.014	0.033	-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	0.037	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	0.037	0.055	-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	0.047	-9999	-0.75	2	2
I kappa B alpha/PIK3R1	0.034	0.055	-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	-0.021	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 S123. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.008	0.25	-9999	-1.1	26	26
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.023	0.073	-9999	-10000	0	0
ATF2/c-Jun	0.044	0.063	-9999	-0.61	1	1
MAPK11	0.022	0.082	-9999	-0.84	1	1
MITF	0.044	0.09	-9999	-10000	0	0
MAPKAPK5	0.044	0.09	-9999	-10000	0	0
KRT8	0.043	0.092	-9999	-10000	0	0
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.032	0.11	-9999	-0.62	1	1
CEBPB	0.034	0.11	-9999	-10000	0	0
SLC9A1	0.044	0.09	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.051	0.095	-9999	-0.82	1	1
p38alpha-beta/MNK1	-0.019	0.073	-9999	-10000	0	0
JUN	0.045	0.063	-9999	-0.6	1	1
PPARGC1A	0.001	0.15	-9999	-0.75	2	2
USF1	0.044	0.09	-9999	-10000	0	0
RAB5/GDP/GDI1	-0.013	0.05	-9999	-10000	0	0
NOS2	0.039	0.13	-9999	-0.84	7	7
DDIT3	0.041	0.095	-9999	-10000	0	0
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.047	0.085	-9999	-0.67	2	2
p38alpha-beta/HBP1	-0.019	0.073	-9999	-10000	0	0
CREB1	0.049	0.093	-9999	-10000	0	0
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.048	0.078	-9999	-10000	0	0
RPS6KA4	0.044	0.09	-9999	-10000	0	0
PLA2G4A	0.043	0.099	-9999	-0.79	2	2
GDI1	0.044	0.09	-9999	-10000	0	0
TP53	0.046	0.11	-9999	-0.5	1	1
RPS6KA5	0.044	0.09	-9999	-10000	0	0
ESR1	0.04	0.097	-9999	-10000	0	0
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.044	0.09	-9999	-10000	0	0
MEF2A	0.044	0.09	-9999	-10000	0	0
EIF4EBP1	0.043	0.098	-9999	-0.46	2	2
KRT19	-0.043	0.21	-9999	-0.88	9	9
ELK4	0.044	0.09	-9999	-10000	0	0
ATF6	0.044	0.09	-9999	-10000	0	0
ATF1	0.049	0.093	-9999	-10000	0	0
p38alpha-beta/MAPKAPK2	-0.019	0.073	-9999	-10000	0	0
p38alpha-beta/MAPKAPK3	-0.019	0.073	-9999	-0.5	1	1

×

IGF1 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	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	0.056	-10000	0	-10000	0	0
GRB2/SOS1/SHC	-0.001	0.025	-10000	0	-0.58	1	1
HRAS	0.014	0.039	-10000	0	-0.86	1	1
IRS1/Crk	-0.007	0.051	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.056	-10000	0	-0.52	6	6
AKT1	0.054	0.062	-10000	0	-0.71	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	0.056	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.052	-10000	0	-10000	0	0
RAF1	0.067	0.058	-10000	0	-0.7	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.007	0.048	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.008	0.057	-10000	0	-0.45	6	6
PIK3CA	0.014	0.033	-10000	0	-0.75	1	1
RPS6KB1	0.054	0.062	-10000	0	-0.71	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	0.033	-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	0.049	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.049	-10000	0	-0.51	1	1
IGF-1R heterotetramer	0.015	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.052	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.007	0.047	-10000	0	-10000	0	0
IGF1R	0.015	0.012	-10000	0	-10000	0	0
IGF1	0.006	0.093	-10000	0	-0.85	6	6
IRS2/Crk	0.029	0.084	-10000	0	-0.49	8	8
PI3K	-0.008	0.053	-10000	0	-10000	0	0
apoptosis	-0.065	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	0.051	-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	-0.71	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.007	0.044	-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	0.033	-10000	0	-0.75	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.006	0.054	-10000	0	-0.47	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.007	0.051	-10000	0	-10000	0	0
GRB10	0.016	0	-10000	0	-10000	0	0
PTPN11	0.029	0.056	-10000	0	-10000	0	0
IRS1	0.018	0.06	-10000	0	-0.45	6	6
IRS2	0.02	0.088	-10000	0	-0.47	14	14
IGF-1R heterotetramer/IGF1	-0.008	0.07	-10000	0	-0.66	6	6
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	0.044	0.065	-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

×

Alternative NF-kappaB pathway

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
IKK alpha homodimer	-0.005	0.058	-9999	-0.67	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	-0.49	4	4
NFKB1	0.014	0.033	-9999	-0.75	1	1
MAP3K14	0.009	0.077	-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 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
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	0.033	-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

×

Nectin adhesion pathway

Figure S127. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S127. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.004	0.049	-9999	-0.56	4	4
PTK2	-0.003	0.03	-9999	-10000	0	0
positive regulation of JNK cascade	-0.002	0.022	-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	0.027	-9999	-10000	0	0
nectin-3/I-afadin	-0.002	0.035	-9999	-0.56	2	2
RAPGEF1	0.075	0.033	-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	0.015	-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	0.033	-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	0.047	-9999	-0.75	2	2
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.75	1	1
CDH1	-0.015	0.15	-9999	-0.75	21	21
CLDN1	0.008	0.079	-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	0.01	0.067	-9999	-0.75	4	4
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.069	0.044	-9999	-0.54	1	1
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	0.029	-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	0.029	-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	0.022	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.003	0.033	-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	0.029	-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	0.023	-9999	-10000	0	0
PTPRM	-0.001	0.016	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.073	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	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	0.033	-9999	-0.75	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.024	-9999	-0.56	1	1
MAP2K4	0.063	0.017	-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	0.033	-9999	-0.75	1	1
SMPD1	-0.001	0.017	-9999	-0.27	1	1
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	0.038	-9999	-0.61	2	2
TRAIL/TRAILR3	-0.002	0.038	-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	0.027	-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	0.014	-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	0.033	-9999	-0.74	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	0.024	-9999	-10000	0	0
mol:ceramide	-0.001	0.017	-9999	-0.27	1	1
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.071	0.025	-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	0.029	-9999	-0.48	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.002	0.025	-9999	-0.45	1	1
JNK cascade	-0.001	0.024	-9999	-0.56	1	1
TRAIL (trimer)	0.014	0.033	-9999	-0.74	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	-0.53	2	2
cell death	-0.001	0.016	-9999	-0.27	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.017	-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	0.027	-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	0.067	-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	0.085	-9999	-0.86	5	5
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.011	0.019	-9999	-0.42	1	1
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	0.12	-9999	-0.86	9	9
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	0.018	-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	0.043	0.034	-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	-0.01	0.075	-9999	-0.58	9	9

pid_entity	TCGA.MW.A4EC	TCGA.MM.A564	TCGA.GK.A6C7	TCGA.G6.A5PC
109_MAP3K5	0.074	0.074	0.074	-0.13
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	-3e-15	-0.75	-0.75	0
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	-0.43	-0.43	-0.43	-0.43
30_TGFB1/TGF beta receptor Type II	0.015	0.021	0.015	0.015
84_STAT5B	-0.031	-0.14	-0.031	-0.26
84_STAT5A	-0.031	-0.14	-0.031	-0.26