PARADIGM pathway analysis of mRNASeq expression data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by the Hedgehog family	68
IL23-mediated signaling events	57
TCGA08_retinoblastoma	53
Signaling mediated by p38-alpha and p38-beta	52
Ephrin A reverse signaling	51
IL4-mediated signaling events	50
Wnt signaling	48
FOXA2 and FOXA3 transcription factor networks	47
Syndecan-1-mediated signaling events	44
Glypican 1 network	41

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
Signaling events mediated by the Hedgehog family	0.1838	68	3561	52	-0.26	0.11	1000	-1000	-0.046	-1000
IL23-mediated signaling events	0.1541	57	3425	60	-0.51	0.012	1000	-1000	-0.15	-1000
TCGA08_retinoblastoma	0.1432	53	430	8	-0.1	0.051	1000	-1000	-0.011	-1000
Signaling mediated by p38-alpha and p38-beta	0.1405	52	2315	44	-0.19	0.012	1000	-1000	-0.031	-1000
Ephrin A reverse signaling	0.1378	51	360	7	-0.077	0	1000	-1000	-0.02	-1000
IL4-mediated signaling events	0.1351	50	4593	91	-0.7	0.55	1000	-1000	-0.15	-1000
Wnt signaling	0.1297	48	339	7	-0.13	-0.014	1000	-1000	-0.03	-1000
FOXA2 and FOXA3 transcription factor networks	0.1270	47	2189	46	-0.43	0.014	1000	-1000	-0.12	-1000
Syndecan-1-mediated signaling events	0.1189	44	1528	34	-0.17	0.012	1000	-1000	-0.046	-1000
Glypican 1 network	0.1108	41	1994	48	-0.14	0.023	1000	-1000	-0.032	-1000
TCR signaling in naïve CD8+ T cells	0.1054	39	3643	93	-0.13	0.077	1000	-1000	-0.067	-1000
p75(NTR)-mediated signaling	0.1027	38	4772	125	-0.25	0.032	1000	-1000	-0.085	-1000
BMP receptor signaling	0.1000	37	3025	81	-0.21	0.04	1000	-1000	-0.087	-1000
Class IB PI3K non-lipid kinase events	0.1000	37	111	3	-0.038	-1000	1000	-1000	-0.008	-1000
EPHB forward signaling	0.0973	36	3108	85	-0.13	0.1	1000	-1000	-0.074	-1000
Glypican 2 network	0.0946	35	140	4	-0.039	-0.03	1000	-1000	-0.016	-1000
Noncanonical Wnt signaling pathway	0.0892	33	859	26	-0.13	0.012	1000	-1000	-0.045	-1000
TCGA08_p53	0.0865	32	227	7	-0.077	0.046	1000	-1000	-0.015	-1000
IL12-mediated signaling events	0.0838	31	2702	87	-0.23	0.04	1000	-1000	-0.13	-1000
Reelin signaling pathway	0.0838	31	1764	56	-0.14	0.03	1000	-1000	-0.061	-1000
Signaling events regulated by Ret tyrosine kinase	0.0838	31	2604	82	-0.16	0.012	1000	-1000	-0.076	-1000
Ephrin B reverse signaling	0.0838	31	1497	48	-0.1	0.061	1000	-1000	-0.053	-1000
Syndecan-4-mediated signaling events	0.0838	31	2101	67	-0.16	0.016	1000	-1000	-0.058	-1000
HIF-1-alpha transcription factor network	0.0811	30	2338	76	-0.32	0.019	1000	-1000	-0.17	-1000
amb2 Integrin signaling	0.0784	29	2434	82	-0.25	0.017	1000	-1000	-0.063	-1000
Glucocorticoid receptor regulatory network	0.0784	29	3384	114	-0.47	0.25	1000	-1000	-0.06	-1000
Endothelins	0.0784	29	2830	96	-0.24	0.028	1000	-1000	-0.076	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0730	27	1872	68	-0.25	0.087	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0703	26	2641	99	-0.15	0.018	1000	-1000	-0.077	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0703	26	3189	120	-0.15	0.12	1000	-1000	-0.063	-1000
LPA receptor mediated events	0.0676	25	2592	102	-0.12	0.014	1000	-1000	-0.078	-1000
IGF1 pathway	0.0676	25	1480	57	-0.075	0.025	1000	-1000	-0.082	-1000
Caspase cascade in apoptosis	0.0649	24	1818	74	-0.1	0.029	1000	-1000	-0.039	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0649	24	821	34	-0.047	0.012	1000	-1000	-0.034	-1000
PDGFR-alpha signaling pathway	0.0649	24	1067	44	-0.056	0.019	1000	-1000	-0.046	-1000
Integrins in angiogenesis	0.0649	24	2020	84	-0.13	0.021	1000	-1000	-0.075	-1000
Plasma membrane estrogen receptor signaling	0.0649	24	2085	86	-0.092	0.077	1000	-1000	-0.069	-1000
Visual signal transduction: Rods	0.0649	24	1297	52	-0.14	0.012	1000	-1000	-0.069	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0649	24	1881	78	-0.12	0.06	1000	-1000	-0.084	-1000
Syndecan-2-mediated signaling events	0.0622	23	1610	69	-0.14	0.023	1000	-1000	-0.031	-1000
Nectin adhesion pathway	0.0622	23	1477	63	-0.068	0.027	1000	-1000	-0.064	-1000
Canonical Wnt signaling pathway	0.0622	23	1211	51	-0.25	0.1	1000	-1000	-0.059	-1000
Effects of Botulinum toxin	0.0622	23	604	26	-0.11	0.012	1000	-1000	-0.05	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0622	23	2034	88	-0.12	0.016	1000	-1000	-0.1	-1000
LPA4-mediated signaling events	0.0568	21	256	12	-0.042	0.015	1000	-1000	-0.025	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0568	21	1131	52	-0.12	0.023	1000	-1000	-0.041	-1000
Thromboxane A2 receptor signaling	0.0541	20	2139	105	-0.11	0.032	1000	-1000	-0.06	-1000
Retinoic acid receptors-mediated signaling	0.0541	20	1171	58	-0.14	0.024	1000	-1000	-0.065	-1000
Presenilin action in Notch and Wnt signaling	0.0514	19	1182	61	-0.25	0.038	1000	-1000	-0.056	-1000
Nongenotropic Androgen signaling	0.0514	19	1038	52	-0.068	0.012	1000	-1000	-0.043	-1000
Calcium signaling in the CD4+ TCR pathway	0.0486	18	581	31	-0.16	0.012	1000	-1000	-0.056	-1000
Coregulation of Androgen receptor activity	0.0459	17	1323	76	-0.11	0.029	1000	-1000	-0.032	-1000
Osteopontin-mediated events	0.0459	17	659	38	-0.065	0.012	1000	-1000	-0.088	-1000
Signaling events mediated by PTP1B	0.0459	17	1362	76	-0.14	0.018	1000	-1000	-0.071	-1000
FAS signaling pathway (CD95)	0.0459	17	838	47	-0.071	0.024	1000	-1000	-0.04	-1000
FOXM1 transcription factor network	0.0459	17	875	51	-0.16	0.029	1000	-1000	-0.18	-1000
Visual signal transduction: Cones	0.0432	16	624	38	-0.054	0.007	1000	-1000	-0.035	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0432	16	871	54	-0.14	0.024	1000	-1000	-0.081	-1000
Arf6 signaling events	0.0432	16	996	62	-0.075	0.016	1000	-1000	-0.044	-1000
Fc-epsilon receptor I signaling in mast cells	0.0432	16	1567	97	-0.068	0.025	1000	-1000	-0.071	-1000
IL1-mediated signaling events	0.0432	16	1026	62	-0.076	0.031	1000	-1000	-0.081	-1000
IL6-mediated signaling events	0.0432	16	1270	75	-0.17	0.036	1000	-1000	-0.064	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0405	15	1335	85	-0.051	0.012	1000	-1000	-0.06	-1000
Cellular roles of Anthrax toxin	0.0378	14	574	39	-0.074	0.012	1000	-1000	-0.019	-1000
S1P1 pathway	0.0378	14	512	36	-0.15	0.012	1000	-1000	-0.048	-1000
IL27-mediated signaling events	0.0378	14	739	51	-0.086	0.025	1000	-1000	-0.073	-1000
Regulation of nuclear SMAD2/3 signaling	0.0351	13	1801	136	-0.26	0.053	1000	-1000	-0.06	-1000
a4b1 and a4b7 Integrin signaling	0.0351	13	69	5	-0.013	0.001	1000	-1000	-0.013	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0351	13	496	37	-0.049	0.018	1000	-1000	-0.037	-1000
EGFR-dependent Endothelin signaling events	0.0351	13	284	21	-0.065	0.018	1000	-1000	-0.058	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0351	13	440	33	-0.16	0.036	1000	-1000	-0.035	-1000
Regulation of Androgen receptor activity	0.0351	13	954	70	-0.15	0.024	1000	-1000	-0.055	-1000
Ceramide signaling pathway	0.0324	12	925	76	-0.069	0.035	1000	-1000	-0.046	-1000
Signaling events mediated by HDAC Class III	0.0324	12	498	40	-0.13	0.024	1000	-1000	-0.021	-1000
TRAIL signaling pathway	0.0324	12	594	48	-0.041	0.025	1000	-1000	-0.059	-1000
Syndecan-3-mediated signaling events	0.0324	12	423	35	-0.094	0.032	1000	-1000	-0.038	-1000
IL2 signaling events mediated by PI3K	0.0324	12	753	58	-0.083	0.019	1000	-1000	-0.072	-1000
IL2 signaling events mediated by STAT5	0.0324	12	271	22	-0.022	0.013	1000	-1000	-0.047	-1000
Ras signaling in the CD4+ TCR pathway	0.0324	12	214	17	-0.026	0.019	1000	-1000	-0.036	-1000
ErbB4 signaling events	0.0297	11	805	69	-0.11	0.033	1000	-1000	-0.084	-1000
PLK2 and PLK4 events	0.0297	11	34	3	-0.003	0.003	1000	-1000	-0.015	-1000
JNK signaling in the CD4+ TCR pathway	0.0297	11	195	17	-0.028	0.012	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0297	11	1173	102	-0.18	0.035	1000	-1000	-0.098	-1000
Hedgehog signaling events mediated by Gli proteins	0.0270	10	652	65	-0.24	0.041	1000	-1000	-0.06	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0270	10	474	45	-0.069	0.025	1000	-1000	-0.088	-1000
Signaling events mediated by PRL	0.0270	10	370	34	-0.12	0.02	1000	-1000	-0.031	-1000
EPO signaling pathway	0.0243	9	502	55	-0.038	0.025	1000	-1000	-0.077	-1000
S1P5 pathway	0.0243	9	164	17	-0.029	0.012	1000	-1000	-0.025	-1000
TCGA08_rtk_signaling	0.0243	9	248	26	-0.041	0.033	1000	-1000	-0.017	-1000
S1P4 pathway	0.0243	9	243	25	-0.029	0.018	1000	-1000	-0.024	-1000
ErbB2/ErbB3 signaling events	0.0216	8	573	65	-0.048	0.02	1000	-1000	-0.055	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0216	8	701	83	-0.14	0.058	1000	-1000	-0.058	-1000
Signaling mediated by p38-gamma and p38-delta	0.0216	8	130	15	-0.012	0.014	1000	-1000	-0.028	-1000
Paxillin-dependent events mediated by a4b1	0.0216	8	298	36	-0.044	0.024	1000	-1000	-0.064	-1000
Class I PI3K signaling events	0.0216	8	598	73	-0.071	0.03	1000	-1000	-0.055	-1000
p38 MAPK signaling pathway	0.0216	8	362	44	-0.11	0.024	1000	-1000	-0.062	-1000
Aurora B signaling	0.0216	8	545	67	-0.16	0.016	1000	-1000	-0.057	-1000
BARD1 signaling events	0.0189	7	425	57	-0.014	0.039	1000	-1000	-0.056	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0189	7	223	28	-0.029	0.03	1000	-1000	-0.029	-1000
ceramide signaling pathway	0.0189	7	366	49	-0.069	0.018	1000	-1000	-0.049	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0189	7	557	74	-0.079	0.05	1000	-1000	-0.077	-1000
IFN-gamma pathway	0.0162	6	423	68	-0.11	0.035	1000	-1000	-0.087	-1000
HIF-2-alpha transcription factor network	0.0162	6	298	43	-0.046	0.046	1000	-1000	-0.076	-1000
Regulation of p38-alpha and p38-beta	0.0162	6	326	54	-0.071	0.032	1000	-1000	-0.057	-1000
Insulin Pathway	0.0162	6	514	74	-0.11	0.032	1000	-1000	-0.079	-1000
S1P3 pathway	0.0162	6	262	42	-0.013	0.021	1000	-1000	-0.031	-1000
Rapid glucocorticoid signaling	0.0162	6	121	20	-0.01	0.012	1000	-1000	-0.012	-1000
PDGFR-beta signaling pathway	0.0162	6	602	97	-0.056	0.034	1000	-1000	-0.068	-1000
Signaling events mediated by HDAC Class II	0.0135	5	430	75	-0.059	0.033	1000	-1000	-0.04	-1000
mTOR signaling pathway	0.0135	5	297	53	-0.022	0.016	1000	-1000	-0.056	-1000
Signaling events mediated by HDAC Class I	0.0135	5	547	104	-0.069	0.046	1000	-1000	-0.058	-1000
E-cadherin signaling events	0.0135	5	26	5	0.002	0.016	1000	-1000	-0.019	-1000
Canonical NF-kappaB pathway	0.0108	4	185	39	-0.069	0.059	1000	-1000	-0.075	-1000
Aurora C signaling	0.0108	4	32	7	-0.004	0.011	1000	-1000	-0.023	-1000
Atypical NF-kappaB pathway	0.0108	4	139	31	-0.018	0.029	1000	-1000	-0.037	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0108	4	516	125	-0.068	0.047	1000	-1000	-0.08	-1000
E-cadherin signaling in the nascent adherens junction	0.0108	4	314	76	-0.023	0.041	1000	-1000	-0.072	-1000
E-cadherin signaling in keratinocytes	0.0108	4	194	43	-0.018	0.024	1000	-1000	-0.044	-1000
Aurora A signaling	0.0081	3	207	60	-0.03	0.031	1000	-1000	-0.03	-1000
Insulin-mediated glucose transport	0.0081	3	97	32	-0.056	0.025	1000	-1000	-0.05	-1000
Class I PI3K signaling events mediated by Akt	0.0081	3	205	68	-0.056	0.039	1000	-1000	-0.042	-1000
FoxO family signaling	0.0081	3	207	64	-0.076	0.097	1000	-1000	-0.07	-1000
VEGFR1 specific signals	0.0081	3	197	56	-0.018	0.037	1000	-1000	-0.051	-1000
Circadian rhythm pathway	0.0054	2	47	22	-0.012	0.039	1000	-1000	-0.035	-1000
Arf6 downstream pathway	0.0054	2	100	43	-0.022	0.023	1000	-1000	-0.036	-1000
PLK1 signaling events	0.0054	2	248	85	-0.017	0.03	1000	-1000	-0.037	-1000
Arf6 trafficking events	0.0027	1	125	71	-0.035	0.035	1000	-1000	-0.063	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	21	23	0.003	0.04	1000	-1000	-0.044	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	15	27	-0.001	0.029	1000	-1000	-0.048	-1000
Arf1 pathway	0.0000	0	35	54	-0.004	0.024	1000	-1000	-0.027	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.037	1000	-1000	-0.025	-1000
Total	NA	2322	134131	7203	-14	-1000	131000	-131000	-7.4	-131000

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.18	0.26	-10000	0	-0.7	56	56
IHH	-0.26	0.27	-10000	0	-0.52	184	184
SHH Np/Cholesterol/GAS1	-0.1	0.18	-10000	0	-0.31	138	138
LRPAP1	0.012	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.1	0.17	0.31	138	-10000	0	138
SMO/beta Arrestin2	-0.16	0.22	-10000	0	-0.51	65	65
SMO	-0.17	0.23	-10000	0	-0.54	65	65
AKT1	-0.083	0.15	-10000	0	-0.55	20	20
ARRB2	0.012	0	-10000	0	-10000	0	0
BOC	-0.019	0.12	-10000	0	-0.47	24	24
ADRBK1	0.011	0.024	-10000	0	-0.45	1	1
heart looping	-0.17	0.23	-10000	0	-0.53	66	66
STIL	-0.16	0.2	-10000	0	-0.5	70	70
DHH N/PTCH2	-0.026	0.13	-10000	0	-0.41	38	38
DHH N/PTCH1	-0.15	0.19	-10000	0	-0.5	49	49
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
DHH	-0.024	0.13	-10000	0	-0.51	25	25
PTHLH	-0.2	0.31	-10000	0	-0.82	52	52
determination of left/right symmetry	-0.17	0.23	-10000	0	-0.53	66	66
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
skeletal system development	-0.2	0.31	-10000	0	-0.81	52	52
IHH N/Hhip	-0.22	0.24	-10000	0	-0.39	215	215
DHH N/Hhip	-0.088	0.18	-10000	0	-0.38	97	97
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.17	0.23	-10000	0	-0.53	66	66
pancreas development	-0.099	0.21	-10000	0	-0.51	78	78
HHAT	-0.004	0.093	-10000	0	-0.54	11	11
PI3K	-0.006	0.093	-10000	0	-0.37	23	23
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.09	0.2	-10000	0	-0.49	75	75
somite specification	-0.17	0.23	-10000	0	-0.53	66	66
SHH Np/Cholesterol/PTCH1	-0.17	0.21	-10000	0	-0.51	76	76
SHH Np/Cholesterol/PTCH2	-0.063	0.15	-10000	0	-0.33	63	63
SHH Np/Cholesterol/Megalin	-0.16	0.19	-10000	0	-0.36	130	130
SHH	-0.072	0.17	-10000	0	-0.37	85	85
catabolic process	-0.15	0.2	-10000	0	-0.53	39	39
SMO/Vitamin D3	-0.18	0.23	-10000	0	-0.56	69	69
SHH Np/Cholesterol/Hhip	-0.11	0.18	-10000	0	-0.31	147	147
LRP2	-0.19	0.25	-10000	0	-0.49	149	149
receptor-mediated endocytosis	-0.24	0.24	-10000	0	-0.55	104	104
SHH Np/Cholesterol/BOC	-0.065	0.15	-10000	0	-0.3	100	100
SHH Np/Cholesterol/CDO	-0.058	0.15	-10000	0	-0.34	59	59
mesenchymal cell differentiation	0.11	0.17	0.31	147	-10000	0	147
mol:Vitamin D3	-0.17	0.22	-10000	0	-0.51	76	76
IHH N/PTCH2	-0.16	0.18	-10000	0	-0.37	132	132
CDON	-0.005	0.092	-10000	0	-0.48	13	13
IHH N/PTCH1	-0.16	0.2	-10000	0	-0.53	39	39
Megalin/LRPAP1	-0.13	0.18	-10000	0	-0.34	149	149
PTCH2	-0.014	0.11	-10000	0	-0.5	19	19
SHH Np/Cholesterol	-0.056	0.13	-10000	0	-0.29	85	85
PTCH1	-0.15	0.2	-10000	0	-0.53	39	39
HHIP	-0.099	0.21	-10000	0	-0.51	78	78

×

IL23-mediated signaling events

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.41	0.47	-10000	0	-1.1	88	88
IL23A	-0.43	0.49	-10000	0	-1.1	89	89
NF kappa B1 p50/RelA/I kappa B alpha	-0.43	0.45	-10000	0	-1.1	94	94
positive regulation of T cell mediated cytotoxicity	-0.46	0.54	-10000	0	-1.2	93	93
ITGA3	-0.41	0.46	-10000	0	-1.1	87	87
IL17F	-0.28	0.3	-10000	0	-0.7	85	85
IL12B	-0.017	0.063	-10000	0	-0.49	5	5
STAT1 (dimer)	-0.44	0.51	-10000	0	-1.2	92	92
CD4	-0.4	0.46	-10000	0	-1.1	88	88
IL23	-0.42	0.47	-10000	0	-1.1	90	90
IL23R	-0.06	0.082	-10000	0	-0.47	2	2
IL1B	-0.43	0.5	-10000	0	-1.2	88	88
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.41	0.45	-10000	0	-1.1	84	84
TYK2	-0.003	0.019	-10000	0	-10000	0	0
STAT4	-0.006	0.096	-10000	0	-0.5	13	13
STAT3	0.012	0	-10000	0	-10000	0	0
IL18RAP	-0.036	0.15	-10000	0	-0.51	34	34
IL12RB1	-0.039	0.14	-10000	0	-0.53	26	26
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
IL12Rbeta1/TYK2	-0.029	0.1	-10000	0	-0.39	26	26
IL23R/JAK2	-0.078	0.11	-10000	0	-0.45	8	8
positive regulation of chronic inflammatory response	-0.46	0.54	-10000	0	-1.2	93	93
natural killer cell activation	0.006	0.007	0.042	3	-10000	0	3
JAK2	-0.016	0.09	-10000	0	-0.56	9	9
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
NFKB1	0.01	0.003	-10000	0	-10000	0	0
RELA	0.01	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.4	0.44	-10000	0	-1	90	90
ALOX12B	-0.42	0.48	-10000	0	-1.1	92	92
CXCL1	-0.51	0.54	-10000	0	-1.2	118	118
T cell proliferation	-0.46	0.54	-10000	0	-1.2	93	93
NFKBIA	0.01	0.003	-10000	0	-10000	0	0
IL17A	-0.21	0.24	-10000	0	-0.56	67	67
PI3K	-0.45	0.46	-10000	0	-1.1	94	94
IFNG	-0.023	0.038	-10000	0	-0.11	32	32
STAT3 (dimer)	-0.42	0.43	-10000	0	-1.1	90	90
IL18R1	-0.019	0.12	-10000	0	-0.51	22	22
IL23/IL23R/JAK2/TYK2/SOCS3	-0.24	0.28	-10000	0	-0.65	68	68
IL18/IL18R	-0.037	0.15	-10000	0	-0.36	61	61
macrophage activation	-0.023	0.017	-10000	0	-0.044	82	82
TNF	-0.45	0.52	-10000	0	-1.2	93	93
STAT3/STAT4	-0.44	0.46	-10000	0	-1.1	97	97
STAT4 (dimer)	-0.44	0.52	-10000	0	-1.2	92	92
IL18	-0.014	0.12	-10000	0	-0.52	18	18
IL19	-0.49	0.53	-10000	0	-1.2	108	108
STAT5A (dimer)	-0.43	0.51	-10000	0	-1.2	88	88
STAT1	0.01	0.034	-10000	0	-0.45	2	2
SOCS3	-0.009	0.1	-10000	0	-0.52	15	15
CXCL9	-0.49	0.54	-10000	0	-1.2	108	108
MPO	-0.43	0.49	-10000	0	-1.1	95	95
positive regulation of humoral immune response	-0.46	0.54	-10000	0	-1.2	93	93
IL23/IL23R/JAK2/TYK2	-0.48	0.6	-10000	0	-1.3	93	93
IL6	-0.43	0.48	-10000	0	-1.1	92	92
STAT5A	0.011	0.024	-10000	0	-0.45	1	1
IL2	-0.01	0.091	-10000	0	-0.45	15	15
positive regulation of tyrosine phosphorylation of STAT protein	0.006	0.007	0.042	3	-10000	0	3
CD3E	-0.43	0.5	-10000	0	-1.2	91	91
keratinocyte proliferation	-0.46	0.54	-10000	0	-1.2	93	93
NOS2	-0.44	0.49	-10000	0	-1.1	99	99

×

TCGA08_retinoblastoma

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
CDKN2B	-0.01	0.11	-10000	0	-0.49	17	17
CDKN2C	-0.012	0.12	-10000	0	-0.45	25	25
CDKN2A	-0.1	0.21	-10000	0	-0.46	91	91
CCND2	0.038	0.082	0.2	57	-0.14	2	59
RB1	-0.037	0.097	-10000	0	-0.23	58	58
CDK4	0.051	0.095	0.24	57	-10000	0	57
CDK6	0.042	0.094	0.22	57	-0.16	8	65
G1/S progression	0.037	0.097	0.23	58	-10000	0	58

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.19	0.38	-9999	-0.99	56	56
MKNK1	0.012	0	-9999	-10000	0	0
MAPK14	-0.061	0.13	-9999	-0.42	8	8
ATF2/c-Jun	-0.034	0.12	-9999	-0.49	6	6
MAPK11	-0.065	0.14	-9999	-0.31	73	73
MITF	-0.07	0.16	-9999	-0.36	76	76
MAPKAPK5	-0.065	0.16	-9999	-0.35	72	72
KRT8	-0.067	0.16	-9999	-0.35	73	73
MAPKAPK3	0.012	0	-9999	-10000	0	0
MAPKAPK2	0.012	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.092	0.2	-9999	-0.44	72	72
CEBPB	-0.065	0.16	-9999	-0.35	72	72
SLC9A1	-0.065	0.16	-9999	-0.35	72	72
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.06	0.16	-9999	-0.34	72	72
p38alpha-beta/MNK1	-0.062	0.16	-9999	-0.35	71	71
JUN	-0.033	0.12	-9999	-0.49	6	6
PPARGC1A	-0.15	0.24	-9999	-0.44	119	119
USF1	-0.065	0.16	-9999	-0.35	72	72
RAB5/GDP/GDI1	-0.043	0.11	-9999	-0.39	9	9
NOS2	-0.12	0.29	-9999	-0.88	33	33
DDIT3	-0.065	0.16	-9999	-0.35	72	72
RAB5A	0.012	0	-9999	-10000	0	0
HSPB1	-0.053	0.14	-9999	-0.42	15	15
p38alpha-beta/HBP1	-0.062	0.16	-9999	-0.35	71	71
CREB1	-0.068	0.17	-9999	-0.37	72	72
RAB5/GDP	0.009	0	-9999	-10000	0	0
EIF4E	-0.052	0.14	-9999	-0.49	11	11
RPS6KA4	-0.065	0.16	-9999	-0.35	72	72
PLA2G4A	-0.1	0.2	-9999	-0.49	50	50
GDI1	-0.065	0.16	-9999	-0.35	72	72
TP53	-0.094	0.2	-9999	-0.45	74	74
RPS6KA5	-0.073	0.17	-9999	-0.36	77	77
ESR1	-0.12	0.23	-9999	-0.44	101	101
HBP1	0.012	0	-9999	-10000	0	0
MEF2C	-0.067	0.16	-9999	-0.35	75	75
MEF2A	-0.065	0.16	-9999	-0.35	72	72
EIF4EBP1	-0.069	0.17	-9999	-0.37	72	72
KRT19	-0.085	0.18	-9999	-0.36	88	88
ELK4	-0.065	0.16	-9999	-0.35	72	72
ATF6	-0.065	0.16	-9999	-0.35	72	72
ATF1	-0.068	0.17	-9999	-0.37	72	72
p38alpha-beta/MAPKAPK2	-0.062	0.16	-9999	-0.35	71	71
p38alpha-beta/MAPKAPK3	-0.062	0.16	-9999	-0.35	72	72

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.051	0.13	-9999	-0.31	72	72
EFNA5	-0.077	0.2	-9999	-0.53	61	61
FYN	-0.04	0.12	-9999	-0.28	72	72
neuron projection morphogenesis	-0.051	0.13	-9999	-0.31	72	72
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.051	0.13	-9999	-0.31	72	72
EPHA5	-0.008	0.078	-9999	-0.45	11	11

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.49	0.48	-10000	0	-1.2	79	79
STAT6 (cleaved dimer)	-0.53	0.48	-10000	0	-1.1	118	118
IGHG1	-0.17	0.15	-10000	0	-0.38	11	11
IGHG3	-0.47	0.46	-10000	0	-1.1	110	110
AKT1	-0.26	0.29	-10000	0	-0.77	54	54
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.21	0.29	-10000	0	-0.8	43	43
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.8	51	51
THY1	-0.49	0.48	-10000	0	-1.2	82	82
MYB	-0.012	0.11	-10000	0	-0.54	16	16
HMGA1	0.008	0.044	-10000	0	-0.48	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.33	0.36	-10000	0	-0.8	86	86
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.31	-10000	0	-0.86	44	44
SP1	0.017	0.014	-10000	0	-10000	0	0
INPP5D	-0.002	0.088	-10000	0	-0.53	10	10
SOCS5	0.027	0.015	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.5	0.51	-10000	0	-1.2	106	106
SOCS1	-0.32	0.32	-10000	0	-0.75	83	83
SOCS3	-0.29	0.33	-10000	0	-0.92	49	49
FCER2	-0.41	0.4	-10000	0	-0.98	80	80
PARP14	0.006	0.057	-10000	0	-0.54	4	4
CCL17	-0.54	0.53	-10000	0	-1.3	100	100
GRB2	0.012	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.21	0.24	-10000	0	-0.72	37	37
T cell proliferation	-0.5	0.51	-10000	0	-1.2	96	96
IL4R/JAK1	-0.49	0.49	-10000	0	-1.2	94	94
EGR2	-0.5	0.5	-10000	0	-1.3	80	80
JAK2	-0.028	0.09	-10000	0	-0.57	9	9
JAK3	0.003	0.075	-10000	0	-0.49	8	8
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
JAK1	-0.003	0.063	-10000	0	-0.54	5	5
COL1A2	-0.18	0.25	-10000	0	-1.1	16	16
CCL26	-0.49	0.48	-10000	0	-1.2	83	83
IL4R	-0.52	0.52	-10000	0	-1.3	88	88
PTPN6	0.02	0.05	-10000	0	-0.52	3	3
IL13RA2	-0.55	0.54	-10000	0	-1.3	92	92
IL13RA1	-0.015	0.027	-10000	0	-10000	0	0
IRF4	-0.26	0.44	-10000	0	-1.1	69	69
ARG1	-0.13	0.15	-10000	0	-0.74	8	8
CBL	-0.31	0.33	-10000	0	-0.77	79	79
GTF3A	0.018	0.005	-10000	0	-10000	0	0
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
IL13RA1/JAK2	-0.029	0.073	-10000	0	-0.42	9	9
IRF4/BCL6	-0.24	0.41	-10000	0	-1	62	62
CD40LG	-0.038	0.16	-10000	0	-0.52	35	35
MAPK14	-0.31	0.34	-10000	0	-0.84	68	68
mitosis	-0.25	0.27	-10000	0	-0.72	54	54
STAT6	-0.57	0.63	-10000	0	-1.3	106	106
SPI1	0.001	0.085	-10000	0	-0.51	10	10
RPS6KB1	-0.24	0.26	-10000	0	-0.7	49	49
STAT6 (dimer)	-0.57	0.63	-10000	0	-1.3	106	106
STAT6 (dimer)/PARP14	-0.52	0.53	-10000	0	-1.2	107	107
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.26	0.32	-10000	0	-0.86	45	45
FRAP1	-0.26	0.29	-10000	0	-0.77	54	54
LTA	-0.52	0.52	-10000	0	-1.3	86	86
FES	0.008	0.049	-10000	0	-0.54	3	3
T-helper 1 cell differentiation	0.55	0.56	1.3	106	-10000	0	106
CCL11	-0.52	0.51	-10000	0	-1.2	96	96
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.26	0.31	-10000	0	-0.8	51	51
IL2RG	-0.02	0.13	-10000	0	-0.5	25	25
IL10	-0.53	0.52	-10000	0	-1.3	90	90
IRS1	-0.011	0.11	-10000	0	-0.53	16	16
IRS2	-0.035	0.14	-10000	0	-0.47	36	36
IL4	-0.12	0.11	-10000	0	-0.53	1	1
IL5	-0.49	0.48	-10000	0	-1.2	80	80
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.4	0.39	-10000	0	-0.92	85	85
COL1A1	-0.18	0.24	-10000	0	-1.1	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.5	0.5	-10000	0	-1.3	82	82
IL2R gamma/JAK3	-0.015	0.12	-10000	0	-0.39	30	30
TFF3	-0.7	0.65	-10000	0	-1.4	138	138
ALOX15	-0.58	0.56	-10000	0	-1.3	105	105
MYBL1	0.007	0.055	-10000	0	-0.52	4	4
T-helper 2 cell differentiation	-0.42	0.4	-10000	0	-0.96	97	97
SHC1	0.012	0	-10000	0	-10000	0	0
CEBPB	0.015	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.3	-10000	0	-0.74	58	58
mol:PI-3-4-5-P3	-0.26	0.29	-10000	0	-0.77	54	54
PI3K	-0.28	0.32	-10000	0	-0.83	54	54
DOK2	0	0.078	-10000	0	-0.49	9	9
ETS1	0.024	0.03	-10000	0	-0.5	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.23	-10000	0	-0.71	32	32
ITGB3	-0.54	0.53	-10000	0	-1.3	97	97
PIGR	-0.7	0.66	-10000	0	-1.5	136	136
IGHE	0.041	0.041	0.27	3	-10000	0	3
MAPKKK cascade	-0.19	0.22	-10000	0	-0.69	32	32
BCL6	0.011	0.029	-10000	0	-0.54	1	1
OPRM1	-0.5	0.48	-10000	0	-1.2	91	91
RETNLB	-0.49	0.48	-10000	0	-1.2	80	80
SELP	-0.54	0.56	-10000	0	-1.4	92	92
AICDA	-0.48	0.47	-10000	0	-1.2	85	85

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.12	0.2	-9999	-0.43	68	68
FZD6	0.008	0.049	-9999	-0.54	3	3
WNT6	-0.12	0.22	-9999	-0.48	98	98
WNT4	-0.054	0.17	-9999	-0.5	48	48
FZD3	0.012	0	-9999	-10000	0	0
WNT5A	-0.014	0.12	-9999	-0.52	18	18
WNT11	-0.13	0.23	-9999	-0.5	104	104

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.26	0.37	-9999	-0.94	53	53
PCK1	-0.4	0.48	-9999	-1	109	109
HNF4A	-0.43	0.52	-9999	-1.1	104	104
KCNJ11	-0.27	0.4	-9999	-1	54	54
AKT1	-0.09	0.14	-9999	-0.49	7	7
response to starvation	-0.01	0.026	-9999	-10000	0	0
DLK1	-0.28	0.4	-9999	-1	59	59
NKX2-1	-0.055	0.24	-9999	-0.65	16	16
ACADM	-0.26	0.38	-9999	-0.97	58	58
TAT	-0.2	0.23	-9999	-0.71	22	22
CEBPB	0.012	0.007	-9999	-10000	0	0
CEBPA	-0.025	0.14	-9999	-0.52	26	26
TTR	-0.36	0.33	-9999	-0.89	77	77
PKLR	-0.27	0.38	-9999	-0.96	57	57
APOA1	-0.43	0.54	-9999	-1.3	81	81
CPT1C	-0.28	0.4	-9999	-0.98	66	66
ALAS1	-0.1	0.17	-9999	-0.62	2	2
TFRC	-0.26	0.29	-9999	-0.91	26	26
FOXF1	-0.003	0.098	-9999	-0.47	15	15
NF1	0.014	0.05	-9999	-0.54	3	3
HNF1A (dimer)	-0.11	0.22	-9999	-0.54	74	74
CPT1A	-0.26	0.37	-9999	-0.94	54	54
HMGCS1	-0.25	0.36	-9999	-0.94	52	52
NR3C1	-0.005	0.095	-9999	-0.52	11	11
CPT1B	-0.27	0.39	-9999	-1	57	57
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	-0.003	0.048	-9999	-0.21	4	4
GCK	-0.29	0.41	-9999	-1	65	65
CREB1	-0.021	0.062	-9999	-10000	0	0
IGFBP1	-0.14	0.2	-9999	-0.71	14	14
PDX1	-0.29	0.42	-9999	-0.99	74	74
UCP2	-0.26	0.38	-9999	-0.98	53	53
ALDOB	-0.27	0.38	-9999	-0.98	52	52
AFP	-0.2	0.21	-9999	-0.54	60	60
BDH1	-0.26	0.37	-9999	-0.94	56	56
HADH	-0.25	0.38	-9999	-0.96	52	52
F2	-0.37	0.46	-9999	-1.1	64	64
HNF1A	-0.11	0.22	-9999	-0.54	74	74
G6PC	-0.16	0.21	-9999	-0.68	28	28
SLC2A2	-0.25	0.33	-9999	-0.91	48	48
INS	-0.002	0.036	-9999	-0.46	1	1
FOXA1	-0.21	0.26	-9999	-0.52	148	148
FOXA3	-0.18	0.25	-9999	-0.53	111	111
FOXA2	-0.3	0.43	-9999	-1	63	63
ABCC8	-0.28	0.4	-9999	-0.98	61	61
ALB	-0.25	0.3	-9999	-0.72	78	78

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.034	-9999	-0.45	2	2
CCL5	-0.034	0.15	-9999	-0.49	34	34
SDCBP	0.012	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.14	0.18	-9999	-0.43	67	67
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.13	0.18	-9999	-0.43	63	63
Syndecan-1/Syntenin	-0.12	0.17	-9999	-0.42	61	61
MAPK3	-0.1	0.16	-9999	-0.44	36	36
HGF/MET	-0.056	0.16	-9999	-0.38	69	69
TGFB1/TGF beta receptor Type II	0.01	0.034	-9999	-0.45	2	2
BSG	0.012	0	-9999	-10000	0	0
keratinocyte migration	-0.13	0.18	-9999	-0.42	63	63
Syndecan-1/RANTES	-0.15	0.19	-9999	-0.44	79	79
Syndecan-1/CD147	-0.11	0.17	-9999	-0.4	61	61
Syndecan-1/Syntenin/PIP2	-0.12	0.17	-9999	-0.41	61	61
LAMA5	0.008	0.047	-9999	-0.51	3	3
positive regulation of cell-cell adhesion	-0.12	0.16	-9999	-0.4	61	61
MMP7	-0.17	0.25	-9999	-0.52	127	127
HGF	-0.043	0.16	-9999	-0.5	40	40
Syndecan-1/CASK	-0.13	0.17	-9999	-0.41	67	67
Syndecan-1/HGF/MET	-0.16	0.21	-9999	-0.46	91	91
regulation of cell adhesion	-0.096	0.16	-9999	-0.43	35	35
HPSE	-0.014	0.11	-9999	-0.49	19	19
positive regulation of cell migration	-0.14	0.18	-9999	-0.43	67	67
SDC1	-0.14	0.18	-9999	-0.43	67	67
Syndecan-1/Collagen	-0.14	0.18	-9999	-0.43	67	67
PPIB	0.012	0	-9999	-10000	0	0
MET	-0.035	0.15	-9999	-0.52	33	33
PRKACA	0.012	0	-9999	-10000	0	0
MMP9	-0.076	0.2	-9999	-0.5	64	64
MAPK1	-0.1	0.16	-9999	-0.44	37	37
homophilic cell adhesion	-0.14	0.18	-9999	-0.42	67	67
MMP1	-0.1	0.21	-9999	-0.5	85	85

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	-0.009	0.1	-10000	0	-0.31	38	38
fibroblast growth factor receptor signaling pathway	-0.01	0.1	-10000	0	-0.31	38	38
LAMA1	-0.14	0.24	-10000	0	-0.52	102	102
PRNP	-0.007	0.099	-10000	0	-0.52	13	13
GPC1/SLIT2	-0.057	0.15	-10000	0	-0.36	74	74
SMAD2	0.023	0.04	-10000	0	-0.28	5	5
GPC1/PrPc/Cu2+	0.001	0.073	-10000	0	-0.33	17	17
GPC1/Laminin alpha1	-0.094	0.18	-10000	0	-0.38	105	105
TDGF1	-0.12	0.23	-10000	0	-0.5	98	98
CRIPTO/GPC1	-0.085	0.17	-10000	0	-0.36	100	100
APP/GPC1	0.013	0.043	-10000	0	-0.36	5	5
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.065	0.15	-10000	0	-0.3	101	101
FLT1	0.008	0.044	-10000	0	-0.48	3	3
GPC1/TGFB/TGFBR1/TGFBR2	0.019	0.045	-10000	0	-0.3	7	7
SERPINC1	0.001	0.063	-10000	0	-0.45	7	7
FYN	-0.065	0.15	-10000	0	-0.3	101	101
FGR	-0.074	0.16	-10000	0	-0.31	108	108
positive regulation of MAPKKK cascade	-0.09	0.19	-10000	0	-0.43	71	71
SLIT2	-0.085	0.2	-10000	0	-0.5	70	70
GPC1/NRG	-0.027	0.12	-10000	0	-0.36	44	44
NRG1	-0.044	0.16	-10000	0	-0.49	41	41
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.016	0.052	-10000	0	-0.28	11	11
LYN	-0.067	0.15	-10000	0	-0.31	101	101
mol:Spermine	0.005	0.043	-10000	0	-0.36	5	5
cell growth	-0.01	0.1	-10000	0	-0.31	38	38
BMP signaling pathway	-0.005	0.06	0.5	5	-10000	0	5
SRC	-0.066	0.15	-10000	0	-0.3	102	102
TGFBR1	0.012	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.051	0.16	-10000	0	-0.47	47	47
GPC1	0.005	0.06	-10000	0	-0.5	5	5
TGFBR1 (dimer)	0.012	0	-10000	0	-10000	0	0
VEGFA	0.009	0.042	-10000	0	-0.45	3	3
BLK	-0.11	0.18	-10000	0	-0.33	142	142
HCK	-0.079	0.16	-10000	0	-0.31	112	112
FGF2	-0.027	0.14	-10000	0	-0.5	28	28
FGFR1	0.002	0.073	-10000	0	-0.53	7	7
VEGFR1 homodimer	0.008	0.044	-10000	0	-0.48	3	3
TGFBR2	0.009	0.04	-10000	0	-0.54	2	2
cell death	0.013	0.043	-10000	0	-0.36	5	5
ATIII/GPC1	0.005	0.066	-10000	0	-0.36	11	11
PLA2G2A/GPC1	-0.033	0.12	-10000	0	-0.33	52	52
LCK	-0.081	0.17	-10000	0	-0.34	108	108
neuron differentiation	-0.027	0.12	-10000	0	-0.36	44	44
PrPc/Cu2+	-0.005	0.072	-10000	0	-0.38	13	13
APP	0.012	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.009	0.04	-10000	0	-0.54	2	2

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.11	0.2	-10000	0	-0.54	56	56
FYN	-0.1	0.3	-10000	0	-0.7	60	60
LAT/GRAP2/SLP76	-0.11	0.23	-10000	0	-0.59	61	61
IKBKB	0.012	0	-10000	0	-10000	0	0
AKT1	-0.056	0.19	-10000	0	-0.45	59	59
B2M	0.003	0.067	-10000	0	-0.52	6	6
IKBKG	-0.029	0.051	-10000	0	-0.15	42	42
MAP3K8	0.006	0.057	-10000	0	-0.54	4	4
mol:Ca2+	-0.024	0.037	-10000	0	-0.097	52	52
integrin-mediated signaling pathway	0.014	0.029	-10000	0	-0.3	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.097	0.28	-10000	0	-0.66	63	63
TRPV6	-0.13	0.23	-10000	0	-0.53	94	94
CD28	-0.029	0.14	-10000	0	-0.53	28	28
SHC1	-0.1	0.29	-10000	0	-0.68	60	60
receptor internalization	-0.11	0.3	-10000	0	-0.74	57	57
PRF1	-0.12	0.34	-10000	0	-0.95	44	44
KRAS	0.012	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
COT/AKT1	-0.038	0.15	-10000	0	-0.36	57	57
LAT	-0.1	0.3	-10000	0	-0.69	61	61
EntrezGene:6955	-0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.053	0.18	-10000	0	-0.52	46	46
CD3E	-0.053	0.17	-10000	0	-0.51	46	46
CD3G	-0.036	0.15	-10000	0	-0.5	34	34
RASGRP2	-0.003	0.035	-10000	0	-0.16	11	11
RASGRP1	-0.058	0.19	-10000	0	-0.44	63	63
HLA-A	-0.005	0.092	-10000	0	-0.53	11	11
RASSF5	0.008	0.047	-10000	0	-0.51	3	3
RAP1A/GTP/RAPL	0.014	0.029	-10000	0	-0.31	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.002	0.058	-10000	0	-0.12	46	46
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.053	0.09	-10000	0	-0.25	54	54
PRKCA	-0.054	0.11	-10000	0	-0.27	63	63
GRAP2	-0.028	0.14	-10000	0	-0.5	29	29
mol:IP3	-0.051	0.2	0.21	65	-0.44	57	122
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.11	0.31	-10000	0	-0.71	57	57
ORAI1	0.077	0.13	0.29	94	-10000	0	94
CSK	-0.11	0.3	-10000	0	-0.7	60	60
B7 family/CD28	-0.11	0.31	-10000	0	-0.75	58	58
CHUK	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.13	0.35	-10000	0	-0.82	60	60
PTPN6	-0.11	0.3	-10000	0	-0.72	58	58
VAV1	-0.11	0.3	-10000	0	-0.68	64	64
Monovalent TCR/CD3	-0.077	0.24	-10000	0	-0.52	65	65
CBL	0.012	0	-10000	0	-10000	0	0
LCK	-0.11	0.32	-10000	0	-0.74	61	61
PAG1	-0.11	0.3	-10000	0	-0.72	60	60
RAP1A	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.13	0.34	-10000	0	-0.82	58	58
CD80	-0.015	0.12	-10000	0	-0.52	18	18
CD86	-0.011	0.11	-10000	0	-0.52	16	16
PDK1/CARD11/BCL10/MALT1	-0.065	0.11	-10000	0	-0.3	55	55
HRAS	0.011	0.024	-10000	0	-0.45	1	1
GO:0035030	-0.088	0.25	-10000	0	-0.6	58	58
CD8A	-0.057	0.18	-10000	0	-0.51	50	50
CD8B	-0.076	0.19	-10000	0	-0.49	65	65
PTPRC	-0.032	0.15	-10000	0	-0.52	31	31
PDK1/PKC theta	-0.083	0.24	-10000	0	-0.56	62	62
CSK/PAG1	-0.1	0.29	-10000	0	-0.72	56	56
SOS1	0.012	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.086	-10000	0	-0.4	16	16
GRAP2/SLP76	-0.13	0.28	-10000	0	-0.67	65	65
STIM1	0.039	0.062	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.081	-10000	0	-0.18	40	40
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.12	0.34	-10000	0	-0.81	57	57
mol:DAG	-0.067	0.16	-10000	0	-0.39	58	58
RAP1A/GDP	0.002	0.026	-10000	0	-0.064	5	5
PLCG1	0.012	0	-10000	0	-10000	0	0
CD247	-0.026	0.14	-10000	0	-0.51	27	27
cytotoxic T cell degranulation	-0.11	0.32	-10000	0	-0.89	44	44
RAP1A/GTP	-0.004	0.011	-10000	0	-0.068	7	7
mol:PI-3-4-5-P3	-0.073	0.23	-10000	0	-0.53	63	63
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.076	0.25	0.23	57	-0.58	57	114
NRAS	0.005	0.064	-10000	0	-0.54	5	5
ZAP70	-0.046	0.16	-10000	0	-0.5	42	42
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.11	0.23	-10000	0	-0.56	64	64
MALT1	0.006	0.054	-10000	0	-0.45	5	5
TRAF6	0.012	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.091	0.21	-10000	0	-0.43	91	91
CARD11	-0.049	0.16	-10000	0	-0.49	45	45
PRKCB	-0.057	0.12	-10000	0	-0.31	56	56
PRKCE	-0.048	0.1	-10000	0	-0.28	51	51
PRKCQ	-0.1	0.27	-10000	0	-0.62	67	67
LCP2	0	0.079	-10000	0	-0.5	9	9
BCL10	0.012	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.044	0.16	-10000	0	-0.38	59	59
IKK complex	0.005	0.058	-10000	0	-0.11	37	37
RAS family/GDP	-0.006	0.012	-10000	0	-0.076	3	3
MAP3K14	-0.021	0.12	-10000	0	-0.28	47	47
PDPK1	-0.05	0.18	-10000	0	-0.43	57	57
TCR/CD3/MHC I/CD8/Fyn	-0.13	0.36	-10000	0	-0.81	64	64

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.018	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.009	0.097	-10000	0	-0.35	27	27
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.047	0.14	-10000	0	-0.31	61	61
NGF (dimer)/p75(NTR)/BEX1	-0.15	0.21	-10000	0	-0.36	168	168
NT-4/5 (dimer)/p75(NTR)	-0.1	0.18	-10000	0	-0.37	116	116
IKBKB	0.012	0	-10000	0	-10000	0	0
AKT1	-0.063	0.15	-10000	0	-0.47	19	19
IKBKG	0.012	0	-10000	0	-10000	0	0
BDNF	-0.087	0.2	-10000	0	-0.48	74	74
MGDIs/NGR/p75(NTR)/LINGO1	-0.072	0.17	-10000	0	-0.34	99	99
FURIN	0.011	0.029	-10000	0	-0.54	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.092	0.17	-10000	0	-0.32	125	125
LINGO1	-0.035	0.14	-10000	0	-0.47	36	36
Sortilin/TRAF6/NRIF	-0.004	0.028	-10000	0	-10000	0	0
proBDNF (dimer)	-0.087	0.2	-10000	0	-0.48	74	74
NTRK1	-0.043	0.16	-10000	0	-0.5	40	40
RTN4R	-0.008	0.1	-10000	0	-0.49	15	15
neuron apoptosis	-0.074	0.16	-10000	0	-0.43	29	29
IRAK1	0.012	0	-10000	0	-10000	0	0
SHC1	-0.068	0.16	-10000	0	-0.32	99	99
ARHGDIA	0.012	0	-10000	0	-10000	0	0
RhoA/GTP	0.009	0	-10000	0	-10000	0	0
Gamma Secretase	0.032	0.037	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.063	0.16	-10000	0	-0.34	61	61
MAGEH1	-0.007	0.096	-10000	0	-0.49	14	14
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.068	0.16	-10000	0	-0.35	67	67
Mammalian IAPs/DIABLO	-0.003	0.099	-10000	0	-0.3	28	28
proNGF (dimer)	-0.045	0.16	-10000	0	-0.5	41	41
MAGED1	0.002	0.075	-10000	0	-0.54	7	7
APP	0.012	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.068	0.18	-10000	0	-0.49	57	57
ZNF274	0.011	0.024	-10000	0	-0.45	1	1
RhoA/GDP/RHOGDI	-0.05	0.14	-10000	0	-0.31	56	56
NGF	-0.045	0.16	-10000	0	-0.5	41	41
cell cycle arrest	-0.043	0.15	-10000	0	-0.48	11	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.03	0.11	-10000	0	-0.34	11	11
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.081	0.16	-10000	0	-0.31	116	116
NCSTN	0.012	0	-10000	0	-10000	0	0
mol:GTP	-0.072	0.16	-10000	0	-0.33	102	102
PSENEN	0.011	0.029	-10000	0	-0.54	1	1
mol:ceramide	-0.055	0.14	-10000	0	-0.33	57	57
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.018	0.097	-10000	0	-0.38	6	6
p75(NTR)/beta APP	-0.049	0.14	-10000	0	-0.34	69	69
BEX1	-0.13	0.23	-10000	0	-0.49	103	103
mol:GDP	-0.076	0.16	-10000	0	-0.32	99	99
NGF (dimer)	-0.15	0.19	-10000	0	-0.36	127	127
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.057	0.16	-10000	0	-0.37	51	51
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
RAC1/GTP	-0.057	0.14	-10000	0	-0.27	99	99
MYD88	0.012	0	-10000	0	-10000	0	0
CHUK	0.012	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.072	0.16	-10000	0	-0.33	102	102
RHOB	0.011	0.029	-10000	0	-0.54	1	1
RHOA	0.012	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.011	0.051	-10000	0	-0.33	8	8
NT3 (dimer)	-0.067	0.18	-10000	0	-0.48	59	59
TP53	-0.07	0.15	-10000	0	-0.45	19	19
PRDM4	-0.055	0.14	-10000	0	-0.33	56	56
BDNF (dimer)	-0.25	0.24	-10000	0	-0.47	162	162
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
SORT1	0.012	0	-10000	0	-10000	0	0
activation of caspase activity	-0.049	0.14	-10000	0	-0.3	61	61
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.053	0.15	-10000	0	-0.33	56	56
RHOC	0.012	0	-10000	0	-10000	0	0
XIAP	0.012	0	-10000	0	-10000	0	0
MAPK10	-0.075	0.17	-10000	0	-0.43	38	38
DIABLO	0.012	0	-10000	0	-10000	0	0
SMPD2	-0.056	0.14	-10000	0	-0.33	57	57
APH1B	0.006	0.057	-10000	0	-0.54	4	4
APH1A	0.011	0.024	-10000	0	-0.45	1	1
proNGF (dimer)/p75(NTR)/Sortilin	-0.067	0.16	-10000	0	-0.32	99	99
PSEN1	0.012	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.017	0.017	-10000	0	-0.31	1	1
NT3 (dimer)/p75(NTR)	-0.1	0.19	-10000	0	-0.38	112	112
MAPK8	-0.056	0.14	-10000	0	-0.42	20	20
MAPK9	-0.054	0.14	-10000	0	-0.42	19	19
APAF1	0.012	0	-10000	0	-10000	0	0
NTF3	-0.067	0.18	-10000	0	-0.48	59	59
NTF4	-0.068	0.18	-10000	0	-0.49	57	57
NDN	-0.016	0.12	-10000	0	-0.51	20	20
RAC1/GDP	0.009	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.068	0.12	-10000	0	-0.44	14	14
p75 CTF/Sortilin/TRAF6/NRIF	0.029	0.027	-10000	0	-0.28	2	2
RhoA-B-C/GTP	-0.072	0.16	-10000	0	-0.32	102	102
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.065	0.15	-10000	0	-0.47	18	18
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.075	0.16	-10000	0	-0.35	58	58
PRKACB	0.003	0.07	-10000	0	-0.54	6	6
proBDNF (dimer)/p75 ECD	-0.055	0.15	-10000	0	-0.34	75	75
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.047	0.16	-10000	0	-0.51	42	42
BIRC2	0.009	0.04	-10000	0	-0.54	2	2
neuron projection morphogenesis	-0.049	0.16	0.18	32	-0.36	51	83
BAD	-0.057	0.15	-10000	0	-0.41	25	25
RIPK2	0.01	0.037	-10000	0	-0.5	2	2
NGFR	-0.081	0.2	-10000	0	-0.49	69	69
CYCS	-0.052	0.14	-10000	0	-0.47	13	13
ADAM17	0.009	0.04	-10000	0	-0.54	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.054	0.15	-10000	0	-0.33	57	57
BCL2L11	-0.057	0.15	-10000	0	-0.41	24	24
BDNF (dimer)/p75(NTR)	-0.12	0.2	-10000	0	-0.38	125	125
PI3K	-0.071	0.16	-10000	0	-0.34	72	72
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.053	0.15	-10000	0	-0.33	57	57
NDNL2	0.011	0.024	-10000	0	-0.45	1	1
YWHAE	0.012	0	-10000	0	-10000	0	0
PRKCI	0.008	0.044	-10000	0	-0.48	3	3
NGF (dimer)/p75(NTR)	-0.089	0.18	-10000	0	-0.38	99	99
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.058	0.15	-10000	0	-0.33	63	63
TRAF6	0.012	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.04	-10000	0	-0.54	2	2
PLG	-0.079	0.19	-10000	0	-0.47	69	69
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.093	0.17	-10000	0	-0.42	50	50
SQSTM1	0.011	0.024	-10000	0	-0.45	1	1
NGFRAP1	0.005	0.064	-10000	0	-0.54	5	5
CASP3	-0.052	0.14	-10000	0	-0.38	24	24
E2F1	0.003	0.067	-10000	0	-0.48	7	7
CASP9	0.011	0.024	-10000	0	-0.45	1	1
IKK complex	-0.067	0.12	-10000	0	-0.42	21	21
NGF (dimer)/TRKA	-0.062	0.16	-10000	0	-0.38	74	74
MMP7	-0.17	0.25	-10000	0	-0.52	127	127
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.044	0.14	-10000	0	-0.47	11	11
MMP3	-0.12	0.22	-10000	0	-0.49	100	100
APAF-1/Caspase 9	-0.075	0.12	-10000	0	-0.4	24	24

×

BMP receptor 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
BMP7/BMPR2/BMPR1A-1B/FS	-0.15	0.2	-9999	-0.38	127	127
SMAD6-7/SMURF1	0.023	0.027	-9999	-0.32	1	1
NOG	-0.084	0.2	-9999	-0.51	68	68
SMAD9	-0.056	0.17	-9999	-0.6	25	25
SMAD4	0.011	0.029	-9999	-0.54	1	1
SMAD5	-0.047	0.14	-9999	-0.42	29	29
BMP7/USAG1	-0.21	0.23	-9999	-0.41	199	199
SMAD5/SKI	-0.039	0.13	-9999	-0.42	23	23
SMAD1	0.027	0.031	-9999	-10000	0	0
BMP2	-0.071	0.19	-9999	-0.48	62	62
SMAD1/SMAD1/SMAD4	-0.003	0.025	-9999	-10000	0	0
BMPR1A	0.011	0.029	-9999	-0.54	1	1
BMPR1B	-0.055	0.18	-9999	-0.53	46	46
BMPR1A-1B/BAMBI	-0.073	0.17	-9999	-0.34	101	101
AHSG	-0.007	0.082	-9999	-0.45	12	12
CER1	-0.004	0.062	-9999	-0.45	7	7
BMP2-4/CER1	-0.089	0.17	-9999	-0.31	122	122
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.059	0.15	-9999	-0.43	31	31
BMP2-4 (homodimer)	-0.1	0.19	-9999	-0.37	117	117
RGMB	0.012	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.028	0.13	-9999	-0.32	52	52
RGMA	-0.048	0.17	-9999	-0.52	42	42
SMURF1	0.011	0.024	-9999	-0.45	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.066	0.15	-9999	-0.42	38	38
BMP2-4/USAG1	-0.17	0.21	-9999	-0.35	194	194
SMAD6/SMURF1/SMAD5	-0.039	0.13	-9999	-0.43	23	23
SOSTDC1	-0.14	0.24	-9999	-0.5	110	110
BMP7/BMPR2/BMPR1A-1B	-0.1	0.18	-9999	-0.35	93	93
SKI	0.012	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.024	0.13	-9999	-0.48	27	27
HFE2	-0.003	0.058	-9999	-0.45	6	6
ZFYVE16	0.012	0	-9999	-10000	0	0
MAP3K7	0.012	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.11	0.19	-9999	-0.44	58	58
SMAD5/SMAD5/SMAD4	-0.039	0.13	-9999	-0.44	23	23
MAPK1	0.011	0.024	-9999	-0.45	1	1
TAK1/TAB family	-0.069	0.12	-9999	-0.43	24	24
BMP7 (homodimer)	-0.16	0.24	-9999	-0.49	130	130
NUP214	0.012	0	-9999	-10000	0	0
BMP6/FETUA	-0.021	0.11	-9999	-0.34	38	38
SMAD1/SKI	0.033	0.031	-9999	-10000	0	0
SMAD6	0.01	0.037	-9999	-0.5	2	2
CTDSP2	0.012	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.091	0.17	-9999	-0.42	41	41
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.075	0.19	-9999	-0.5	63	63
BMPR2 (homodimer)	0.012	0	-9999	-10000	0	0
GADD34/PP1CA	0.024	0.021	-9999	-0.26	2	2
BMPR1A-1B (homodimer)	-0.032	0.13	-9999	-0.38	47	47
CHRDL1	-0.13	0.23	-9999	-0.49	102	102
ENDOFIN/SMAD1	0.033	0.031	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.04	0.037	-9999	-10000	0	0
SMAD6/SMURF1	0.011	0.024	-9999	-0.45	1	1
BAMBI	-0.079	0.2	-9999	-0.5	66	66
SMURF2	0.012	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.16	0.21	-9999	-0.44	89	89
BMP2-4/GREM1	-0.13	0.2	-9999	-0.42	77	77
SMAD7	0.012	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.047	0.16	-9999	-0.56	26	26
SMAD1/SMAD6	0.032	0.033	-9999	-10000	0	0
TAK1/SMAD6	0.017	0.017	-9999	-0.31	1	1
BMP7	-0.16	0.24	-9999	-0.49	130	130
BMP6	-0.024	0.13	-9999	-0.48	27	27
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.056	0.14	-9999	-0.4	31	31
PPM1A	0.012	0	-9999	-10000	0	0
SMAD1/SMURF2	0.033	0.031	-9999	-10000	0	0
SMAD7/SMURF1	0.017	0.017	-9999	-0.31	1	1
CTDSPL	0.011	0.029	-9999	-0.54	1	1
PPP1CA	0.012	0	-9999	-10000	0	0
XIAP	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
PPP1R15A	0.01	0.034	-9999	-0.45	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.12	0.2	-9999	-0.47	63	63
CHRD	-0.039	0.16	-9999	-0.5	37	37
BMPR2	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.075	0.16	-9999	-0.44	38	38
BMP4	-0.077	0.19	-9999	-0.47	69	69
FST	-0.11	0.21	-9999	-0.48	88	88
BMP2-4/NOG	-0.14	0.2	-9999	-0.34	164	164
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.093	0.17	-9999	-0.5	25	25

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.037	0.15	0.48	37	-10000	0	37
PI3K Class IB/PDE3B	-0.038	0.15	-10000	0	-0.49	37	37
PDE3B	-0.038	0.15	-10000	0	-0.49	37	37

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.077	0.16	-10000	0	-0.32	102	102
cell-cell adhesion	0.1	0.15	0.44	46	-10000	0	46
Ephrin B/EPHB2/RasGAP	-0.062	0.17	-10000	0	-0.34	81	81
ITSN1	0.011	0.024	-10000	0	-0.45	1	1
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
SHC1	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.037	0.12	-10000	0	-0.31	61	61
Ephrin B1/EPHB1	-0.044	0.12	-10000	0	-0.29	73	73
HRAS/GDP	-0.09	0.14	-10000	0	-0.41	39	39
Ephrin B/EPHB1/GRB7	-0.09	0.19	-10000	0	-0.51	36	36
Endophilin/SYNJ1	-0.061	0.16	-10000	0	-0.32	82	82
KRAS	0.012	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.079	0.18	-10000	0	-0.5	30	30
endothelial cell migration	-0.005	0.091	-10000	0	-0.28	30	30
GRB2	0.012	0	-10000	0	-10000	0	0
GRB7	-0.014	0.11	-10000	0	-0.47	20	20
PAK1	-0.061	0.17	-10000	0	-0.54	25	25
HRAS	0.011	0.024	-10000	0	-0.45	1	1
RRAS	-0.062	0.16	-10000	0	-0.32	81	81
DNM1	-0.012	0.11	-10000	0	-0.48	18	18
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.076	0.16	-10000	0	-0.32	87	87
lamellipodium assembly	-0.1	0.15	-10000	0	-0.44	46	46
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.051	0.14	-10000	0	-0.41	24	24
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
EPHB2	-0.051	0.17	-10000	0	-0.51	45	45
EPHB3	-0.069	0.19	-10000	0	-0.5	59	59
EPHB1	-0.08	0.19	-10000	0	-0.48	69	69
EPHB4	0.009	0.04	-10000	0	-0.54	2	2
mol:GDP	-0.059	0.17	-10000	0	-0.36	61	61
Ephrin B/EPHB2	-0.069	0.17	-10000	0	-0.35	81	81
Ephrin B/EPHB3	-0.078	0.18	-10000	0	-0.36	82	82
JNK cascade	-0.051	0.14	-10000	0	-0.46	17	17
Ephrin B/EPHB1	-0.084	0.17	-10000	0	-0.34	87	87
RAP1/GDP	-0.041	0.15	-10000	0	-0.4	25	25
EFNB2	-0.011	0.11	-10000	0	-0.5	17	17
EFNB3	-0.082	0.2	-10000	0	-0.52	66	66
EFNB1	0.007	0.055	-10000	0	-0.52	4	4
Ephrin B2/EPHB1-2	-0.076	0.17	-10000	0	-0.32	106	106
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.17	-10000	0	-0.49	45	45
Rap1/GTP	-0.1	0.16	-10000	0	-0.45	45	45
axon guidance	-0.077	0.16	-10000	0	-0.32	102	102
MAPK3	-0.035	0.12	-10000	0	-0.39	20	20
MAPK1	-0.035	0.12	-10000	0	-0.39	20	20
Rac1/GDP	-0.048	0.16	-10000	0	-0.37	40	40
actin cytoskeleton reorganization	-0.085	0.12	-10000	0	-0.37	38	38
CDC42/GDP	-0.048	0.16	-10000	0	-0.38	36	36
PI3K	-0.002	0.092	-10000	0	-0.28	30	30
EFNA5	-0.077	0.2	-10000	0	-0.53	61	61
Ephrin B2/EPHB4	0	0.071	-10000	0	-0.3	19	19
Ephrin B/EPHB2/Intersectin/N-WASP	-0.052	0.16	-10000	0	-0.52	21	21
CDC42	0.012	0	-10000	0	-10000	0	0
RAS family/GTP	-0.1	0.15	-10000	0	-0.44	45	45
PTK2	0.02	0.033	-10000	0	-10000	0	0
MAP4K4	-0.051	0.14	-10000	0	-0.46	17	17
SRC	0.009	0.04	-10000	0	-0.54	2	2
KALRN	0.002	0.075	-10000	0	-0.54	7	7
Intersectin/N-WASP	0.017	0.017	-10000	0	-0.31	1	1
neuron projection morphogenesis	-0.054	0.16	-10000	0	-0.4	35	35
MAP2K1	-0.042	0.13	-10000	0	-0.41	20	20
WASL	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.059	0.16	-10000	0	-0.34	61	61
cell migration	-0.044	0.15	-10000	0	-0.45	20	20
NRAS	0.005	0.064	-10000	0	-0.54	5	5
SYNJ1	-0.062	0.16	-10000	0	-0.32	82	82
PXN	0.012	0	-10000	0	-10000	0	0
TF	-0.084	0.18	-10000	0	-0.52	33	33
HRAS/GTP	-0.11	0.17	-10000	0	-0.47	45	45
Ephrin B1/EPHB1-2	-0.066	0.16	-10000	0	-0.3	102	102
cell adhesion mediated by integrin	0.069	0.14	0.32	70	-10000	0	70
RAC1	0.012	0	-10000	0	-10000	0	0
mol:GTP	-0.097	0.19	-10000	0	-0.51	45	45
RAC1-CDC42/GTP	-0.13	0.18	-10000	0	-0.46	62	62
RASA1	0.012	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.041	0.15	-10000	0	-0.4	25	25
ruffle organization	-0.075	0.18	-10000	0	-0.45	46	46
NCK1	0.012	0	-10000	0	-10000	0	0
receptor internalization	-0.065	0.17	-10000	0	-0.5	30	30
Ephrin B/EPHB2/KALRN	-0.068	0.18	-10000	0	-0.35	84	84
ROCK1	-0.027	0.11	-10000	0	-0.27	61	61
RAS family/GDP	-0.083	0.12	-10000	0	-0.4	30	30
Rac1/GTP	-0.11	0.16	-10000	0	-0.47	46	46
Ephrin B/EPHB1/Src/Paxillin	-0.061	0.15	-10000	0	-0.41	30	30

×

Glypican 2 network

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
MDK	-0.004	0.092	-9999	-0.53	11	11
GPC2	-0.039	0.15	-9999	-0.5	37	37
GPC2/Midkine	-0.03	0.13	-9999	-0.37	46	46
neuron projection morphogenesis	-0.03	0.13	-9999	-0.37	46	46

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.02	0.13	-9999	-0.53	22	22
GNB1/GNG2	-0.1	0.19	-9999	-0.53	39	39
mol:DAG	-0.092	0.17	-9999	-0.47	39	39
PLCG1	-0.095	0.18	-9999	-0.49	39	39
YES1	-0.11	0.19	-9999	-0.55	36	36
FZD3	0.012	0	-9999	-10000	0	0
FZD6	0.008	0.049	-9999	-0.54	3	3
G protein	-0.096	0.18	-9999	-0.5	39	39
MAP3K7	-0.075	0.15	-9999	-0.43	32	32
mol:Ca2+	-0.089	0.17	-9999	-0.46	39	39
mol:IP3	-0.092	0.17	-9999	-0.47	39	39
NLK	-0.004	0.009	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
CAMK2A	-0.087	0.16	-9999	-0.45	36	36
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.12	0.2	-9999	-0.43	68	68
CSNK1A1	0.012	0	-9999	-10000	0	0
GNAS	-0.11	0.19	-9999	-0.56	35	35
GO:0007205	-0.09	0.17	-9999	-0.47	39	39
WNT6	-0.12	0.22	-9999	-0.48	98	98
WNT4	-0.054	0.17	-9999	-0.5	48	48
NFAT1/CK1 alpha	-0.097	0.19	-9999	-0.51	39	39
GNG2	-0.002	0.084	-9999	-0.48	11	11
WNT5A	-0.014	0.12	-9999	-0.52	18	18
WNT11	-0.13	0.23	-9999	-0.5	104	104
CDC42	-0.098	0.18	-9999	-0.52	36	36

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.077	0.15	-10000	0	-0.34	91	91
TP53	-0.038	0.085	-10000	0	-0.37	15	15
Senescence	-0.038	0.084	-10000	0	-0.37	15	15
Apoptosis	-0.038	0.084	-10000	0	-0.37	15	15
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.046	0.089	0.2	89	-0.3	2	91
MDM4	0.012	0	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.04	0.15	-10000	0	-0.41	31	31
TBX21	-0.17	0.46	-10000	0	-1.1	56	56
B2M	0.003	0.067	-10000	0	-0.51	6	6
TYK2	0.011	0.022	-10000	0	-10000	0	0
IL12RB1	-0.025	0.14	-10000	0	-0.52	26	26
GADD45B	-0.12	0.36	-10000	0	-0.91	44	44
IL12RB2	-0.031	0.14	-10000	0	-0.49	32	32
GADD45G	-0.12	0.37	-10000	0	-0.96	39	39
natural killer cell activation	-0.001	0.023	-10000	0	-10000	0	0
RELB	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL18	-0.013	0.12	-10000	0	-0.53	18	18
IL2RA	-0.022	0.13	-10000	0	-0.51	24	24
IFNG	-0.038	0.15	-10000	0	-0.48	36	36
STAT3 (dimer)	-0.11	0.34	-10000	0	-0.78	59	59
HLA-DRB5	-0.063	0.18	-10000	0	-0.51	54	54
FASLG	-0.19	0.49	-10000	0	-1.1	62	62
NF kappa B2 p52/RelB	-0.21	0.37	-10000	0	-0.96	59	59
CD4	-0.004	0.092	-10000	0	-0.53	11	11
SOCS1	0.004	0.066	-10000	0	-0.51	6	6
EntrezGene:6955	-0.001	0.01	-10000	0	-10000	0	0
CD3D	-0.053	0.17	-10000	0	-0.51	46	46
CD3E	-0.053	0.17	-10000	0	-0.51	46	46
CD3G	-0.036	0.15	-10000	0	-0.5	34	34
IL12Rbeta2/JAK2	-0.022	0.12	-10000	0	-0.36	41	41
CCL3	-0.16	0.45	-10000	0	-1.1	56	56
CCL4	-0.16	0.45	-10000	0	-1.1	56	56
HLA-A	-0.004	0.091	-10000	0	-0.52	11	11
IL18/IL18R	-0.023	0.17	-10000	0	-0.39	55	55
NOS2	-0.18	0.46	-10000	0	-1.1	64	64
IL12/IL12R/TYK2/JAK2/SPHK2	-0.036	0.14	-10000	0	-0.37	30	30
IL1R1	-0.16	0.43	-10000	0	-1	57	57
IL4	0.005	0.034	-10000	0	-0.47	1	1
JAK2	-0.003	0.089	-10000	0	-0.55	9	9
EntrezGene:6957	-0.001	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.13	0.36	-10000	0	-0.87	57	57
RAB7A	-0.083	0.3	-10000	0	-0.8	31	31
lysosomal transport	-0.076	0.29	-10000	0	-0.76	31	31
FOS	-0.12	0.33	-10000	0	-0.8	53	53
STAT4 (dimer)	-0.12	0.38	-10000	0	-0.89	55	55
STAT5A (dimer)	-0.23	0.39	-10000	0	-0.96	66	66
GZMA	-0.19	0.5	-10000	0	-1.2	59	59
GZMB	-0.21	0.51	-10000	0	-1.2	65	65
HLX	0.011	0.024	-10000	0	-0.45	1	1
LCK	-0.18	0.48	-10000	0	-1.1	59	59
TCR/CD3/MHC II/CD4	-0.1	0.3	-10000	0	-0.64	62	62
IL2/IL2R	-0.04	0.17	-10000	0	-0.44	45	45
MAPK14	-0.12	0.38	-10000	0	-0.91	47	47
CCR5	-0.14	0.41	-10000	0	-1.1	45	45
IL1B	-0.022	0.13	-10000	0	-0.53	23	23
STAT6	-0.023	0.13	-10000	0	-0.28	26	26
STAT4	-0.006	0.096	-10000	0	-0.5	13	13
STAT3	0.012	0	-10000	0	-10000	0	0
STAT1	0.01	0.034	-10000	0	-0.45	2	2
NFKB1	0.012	0	-10000	0	-10000	0	0
NFKB2	0.012	0	-10000	0	-10000	0	0
IL12B	0.001	0.059	-10000	0	-0.46	5	5
CD8A	-0.058	0.18	-10000	0	-0.5	50	50
CD8B	-0.076	0.19	-10000	0	-0.48	65	65
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.04	0.15	0.4	31	-10000	0	31
IL2RB	-0.023	0.13	-10000	0	-0.51	25	25
proteasomal ubiquitin-dependent protein catabolic process	-0.1	0.35	-10000	0	-0.8	54	54
IL2RG	-0.022	0.13	-10000	0	-0.5	25	25
IL12	-0.035	0.13	-10000	0	-0.34	52	52
STAT5A	0.011	0.024	-10000	0	-0.45	1	1
CD247	-0.026	0.14	-10000	0	-0.51	27	27
IL2	-0.014	0.09	-10000	0	-0.45	15	15
SPHK2	0.012	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.054	0.17	-10000	0	-0.49	47	47
IL12/IL12R/TYK2/JAK2	-0.19	0.53	-10000	0	-1.2	59	59
MAP2K3	-0.12	0.38	-10000	0	-0.9	48	48
RIPK2	0.01	0.037	-10000	0	-0.5	2	2
MAP2K6	-0.13	0.39	-10000	0	-0.93	49	49
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.025	0.14	-10000	0	-0.52	26	26
IL18RAP	-0.035	0.15	-10000	0	-0.51	34	34
IL12Rbeta1/TYK2	-0.009	0.11	-10000	0	-0.39	26	26
EOMES	-0.06	0.26	-10000	0	-1.3	14	14
STAT1 (dimer)	-0.13	0.35	-10000	0	-0.77	65	65
T cell proliferation	-0.081	0.28	-10000	0	-0.64	53	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.018	0.13	-10000	0	-0.52	22	22
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.16	0.26	-10000	0	-0.71	53	53
ATF2	-0.1	0.34	-10000	0	-0.83	45	45

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.01	0.054	-9999	-0.35	8	8
VLDLR	-0.004	0.093	-9999	-0.54	11	11
CRKL	0.012	0	-9999	-10000	0	0
LRPAP1	0.012	0	-9999	-10000	0	0
FYN	0.011	0.024	-9999	-0.45	1	1
ITGA3	0	0.081	-9999	-0.51	9	9
RELN/VLDLR/Fyn	-0.082	0.15	-9999	-0.29	124	124
MAPK8IP1/MKK7/MAP3K11/JNK1	0.03	0.045	-9999	-0.26	8	8
AKT1	-0.065	0.13	-9999	-0.33	26	26
MAP2K7	0.012	0	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0
DAB1	-0.03	0.13	-9999	-0.45	31	31
RELN/LRP8/DAB1	-0.091	0.15	-9999	-0.28	135	135
LRPAP1/LRP8	0.013	0.045	-9999	-0.34	6	6
RELN/LRP8/DAB1/Fyn	-0.08	0.15	-9999	-0.31	69	69
DAB1/alpha3/beta1 Integrin	-0.095	0.13	-9999	-0.42	20	20
long-term memory	-0.12	0.19	-9999	-0.5	45	45
DAB1/LIS1	-0.094	0.13	-9999	-0.42	18	18
DAB1/CRLK/C3G	-0.09	0.12	-9999	-0.4	18	18
PIK3CA	0.01	0.034	-9999	-0.45	2	2
DAB1/NCK2	-0.075	0.14	-9999	-0.43	19	19
ARHGEF2	0.012	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.075	0.19	-9999	-0.48	64	64
CDK5R1	0.001	0.074	-9999	-0.5	8	8
RELN	-0.14	0.23	-9999	-0.49	114	114
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
RELN/LRP8/Fyn	-0.077	0.15	-9999	-0.3	116	116
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.12	0.18	-9999	-0.39	69	69
MAPK8	0.009	0.04	-9999	-0.54	2	2
RELN/VLDLR/DAB1	-0.096	0.15	-9999	-0.28	142	142
ITGB1	0.012	0	-9999	-10000	0	0
MAP1B	-0.1	0.17	-9999	-0.33	95	95
RELN/LRP8	-0.076	0.15	-9999	-0.3	116	116
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.087	0.16	-9999	-0.34	77	77
PI3K	-0.006	0.093	-9999	-0.37	23	23
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.009	0.059	-9999	-0.36	9	9
RAP1A	-0.057	0.13	-9999	-0.38	18	18
PAFAH1B1	0.012	0	-9999	-10000	0	0
MAPK8IP1	0.002	0.073	-9999	-0.53	7	7
CRLK/C3G	0.018	0	-9999	-10000	0	0
GRIN2B	-0.016	0.099	-9999	-0.45	18	18
NCK2	0.011	0.029	-9999	-0.54	1	1
neuron differentiation	-0.026	0.089	-9999	-0.3	6	6
neuron adhesion	-0.05	0.13	-9999	-0.37	20	20
LRP8	0.004	0.062	-9999	-0.48	6	6
GSK3B	-0.056	0.12	-9999	-0.41	11	11
RELN/VLDLR/DAB1/Fyn	-0.085	0.15	-9999	-0.3	76	76
MAP3K11	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.075	0.13	-9999	-0.27	92	92
CDK5	0.012	0	-9999	-10000	0	0
MAPT	-0.002	0.096	-9999	-0.44	16	16
neuron migration	-0.056	0.14	-9999	-0.39	13	13
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.026	0.09	-9999	-0.31	6	6
RELN/VLDLR	-0.07	0.14	-9999	-0.3	68	68

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.025	0.048	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.095	0.12	-9999	-0.37	39	39
JUN	-0.051	0.12	-9999	-0.39	14	14
HRAS	0.011	0.024	-9999	-0.45	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.12	0.18	-9999	-0.39	80	80
RAP1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0	-9999	-10000	0	0
RAP1A/GDP	0.009	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.11	0.18	-9999	-0.37	78	78
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.046	0.13	-9999	-0.28	80	80
RHOA	0.012	0	-9999	-10000	0	0
RAP1A/GTP	-0.11	0.14	-9999	-0.46	27	27
GRB7	-0.014	0.11	-9999	-0.47	20	20
RET51/GFRalpha1/GDNF	-0.11	0.18	-9999	-0.37	78	78
MAPKKK cascade	-0.093	0.13	-9999	-0.4	27	27
BCAR1	0.011	0.029	-9999	-0.54	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.058	0.14	-9999	-0.29	91	91
lamellipodium assembly	-0.089	0.12	-9999	-0.34	43	43
RET51/GFRalpha1/GDNF/SHC	-0.11	0.18	-9999	-0.37	78	78
PIK3CA	0.01	0.034	-9999	-0.45	2	2
RET9/GFRalpha1/GDNF/SHC	-0.044	0.13	-9999	-0.28	79	79
RET9/GFRalpha1/GDNF/Shank3	-0.044	0.13	-9999	-0.28	79	79
MAPK3	-0.084	0.15	-9999	-0.43	27	27
DOK1	0.012	0	-9999	-10000	0	0
DOK6	-0.054	0.17	-9999	-0.49	49	49
PXN	0.012	0	-9999	-10000	0	0
neurite development	-0.083	0.15	-9999	-0.42	32	32
DOK5	-0.076	0.19	-9999	-0.48	66	66
GFRA1	-0.087	0.2	-9999	-0.5	72	72
MAPK8	-0.058	0.12	-9999	-0.41	13	13
HRAS/GTP	-0.11	0.14	-9999	-0.45	27	27
tube development	-0.036	0.12	-9999	-0.3	39	39
MAPK1	-0.084	0.15	-9999	-0.43	28	28
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.022	0.094	-9999	-0.26	39	39
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.009	0.04	-9999	-0.54	2	2
PDLIM7	0.01	0.034	-9999	-0.45	2	2
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.2	-9999	-0.52	51	51
SHC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.11	0.18	-9999	-0.37	78	78
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.21	-9999	-0.44	96	96
PRKCA	-0.013	0.11	-9999	-0.53	17	17
HRAS/GDP	0.008	0.017	-9999	-0.32	1	1
CREB1	-0.045	0.12	-9999	-0.32	38	38
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.023	0.099	-9999	-0.27	39	39
RET51/GFRalpha1/GDNF/Grb7	-0.12	0.19	-9999	-0.38	86	86
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.22	-9999	-0.48	99	99
DOK4	0.012	0	-9999	-10000	0	0
JNK cascade	-0.05	0.12	-9999	-0.38	14	14
RET9/GFRalpha1/GDNF/FRS2	-0.044	0.13	-9999	-0.28	79	79
SHANK3	0.012	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.022	0.095	-9999	-0.26	39	39
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.067	0.13	-9999	-0.35	27	27
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.067	0.13	-9999	-0.35	27	27
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.068	0.14	-9999	-0.38	27	27
PI3K	-0.1	0.2	-9999	-0.52	43	43
SOS1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.035	0.12	-9999	-0.3	39	39
GRB10	0	0.08	-9999	-0.54	8	8
activation of MAPKK activity	-0.054	0.11	-9999	-0.38	14	14
RET51/GFRalpha1/GDNF/FRS2	-0.11	0.18	-9999	-0.37	78	78
GAB1	0.011	0.029	-9999	-0.54	1	1
IRS1	-0.011	0.11	-9999	-0.53	16	16
IRS2	-0.035	0.14	-9999	-0.47	36	36
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.069	0.14	-9999	-0.38	28	28
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.19	-9999	-0.39	87	87
GRB2	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GDNF	-0.011	0.084	-9999	-0.45	13	13
RAC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.19	-9999	-0.38	89	89
Rac1/GTP	-0.1	0.14	-9999	-0.41	42	42
RET9/GFRalpha1/GDNF	-0.058	0.14	-9999	-0.32	79	79
GFRalpha1/GDNF	-0.069	0.16	-9999	-0.37	79	79

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.011	0.11	-10000	0	-0.5	17	17
EPHB2	-0.051	0.17	-10000	0	-0.51	45	45
EFNB1	-0.002	0.091	-10000	0	-0.37	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.058	0.16	-10000	0	-0.47	27	27
Ephrin B2/EPHB1-2	-0.075	0.17	-10000	0	-0.32	106	106
neuron projection morphogenesis	-0.081	0.14	-10000	0	-0.45	27	27
Ephrin B1/EPHB1-2/Tiam1	-0.067	0.17	-10000	0	-0.36	63	63
DNM1	-0.012	0.11	-10000	0	-0.48	18	18
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.043	0.18	-10000	0	-0.63	32	32
YES1	-0.073	0.24	-10000	0	-0.86	31	31
Ephrin B1/EPHB1-2/NCK2	-0.061	0.16	-10000	0	-0.44	31	31
PI3K	-0.056	0.19	-10000	0	-0.52	48	48
mol:GDP	-0.067	0.17	-10000	0	-0.36	63	63
ITGA2B	-0.038	0.15	-10000	0	-0.51	36	36
endothelial cell proliferation	0	0.071	-10000	0	-0.3	19	19
FYN	-0.073	0.24	-10000	0	-0.86	31	31
MAP3K7	-0.05	0.19	-10000	0	-0.68	31	31
FGR	-0.076	0.24	-10000	0	-0.87	31	31
TIAM1	0	0.08	-10000	0	-0.54	8	8
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
RGS3	0.012	0	-10000	0	-10000	0	0
cell adhesion	-0.1	0.22	-10000	0	-0.6	46	46
LYN	-0.074	0.24	-10000	0	-0.86	31	31
Ephrin B1/EPHB1-2/Src Family Kinases	-0.071	0.22	-10000	0	-0.81	31	31
Ephrin B1/EPHB1-2	-0.067	0.2	-10000	0	-0.73	31	31
SRC	-0.074	0.24	-10000	0	-0.86	31	31
ITGB3	-0.068	0.18	-10000	0	-0.48	60	60
EPHB1	-0.081	0.19	-10000	0	-0.48	69	69
EPHB4	0.009	0.04	-10000	0	-0.54	2	2
RAC1	0.012	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.071	-10000	0	-0.3	19	19
alphaIIb/beta3 Integrin	-0.075	0.17	-10000	0	-0.36	92	92
BLK	-0.089	0.25	-10000	0	-0.88	31	31
HCK	-0.078	0.24	-10000	0	-0.86	31	31
regulation of stress fiber formation	0.061	0.16	0.43	31	-10000	0	31
MAPK8	-0.036	0.18	-10000	0	-0.61	31	31
Ephrin B1/EPHB1-2/RGS3	-0.061	0.16	-10000	0	-0.46	26	26
endothelial cell migration	-0.05	0.18	-10000	0	-0.51	43	43
NCK2	0.011	0.029	-10000	0	-0.54	1	1
PTPN13	-0.05	0.19	-10000	0	-0.62	37	37
regulation of focal adhesion formation	0.061	0.16	0.43	31	-10000	0	31
chemotaxis	0.061	0.16	0.46	26	-10000	0	26
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
Rac1/GTP	-0.078	0.14	-10000	0	-0.46	27	27
angiogenesis	-0.067	0.2	-10000	0	-0.73	31	31
LCK	-0.08	0.24	-10000	0	-0.84	32	32

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.01	0.085	-9999	-0.51	6	6
Syndecan-4/Syndesmos	-0.088	0.19	-9999	-0.5	49	49
positive regulation of JNK cascade	-0.098	0.18	-9999	-0.47	52	52
Syndecan-4/ADAM12	-0.099	0.2	-9999	-0.5	53	53
CCL5	-0.034	0.15	-9999	-0.49	34	34
Rac1/GDP	0.009	0	-9999	-10000	0	0
DNM2	0.012	0	-9999	-10000	0	0
ITGA5	0.01	0.037	-9999	-0.5	2	2
SDCBP	0.012	0	-9999	-10000	0	0
PLG	-0.076	0.19	-9999	-0.47	69	69
ADAM12	-0.012	0.11	-9999	-0.48	18	18
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.029	0.039	-9999	-0.18	2	2
Syndecan-4/Laminin alpha1	-0.16	0.22	-9999	-0.52	74	74
Syndecan-4/CXCL12/CXCR4	-0.1	0.2	-9999	-0.5	52	52
Syndecan-4/Laminin alpha3	-0.11	0.21	-9999	-0.52	55	55
MDK	-0.004	0.092	-9999	-0.53	11	11
Syndecan-4/FZD7	-0.12	0.21	-9999	-0.49	67	67
Syndecan-4/Midkine	-0.096	0.2	-9999	-0.5	53	53
FZD7	-0.061	0.18	-9999	-0.5	53	53
Syndecan-4/FGFR1/FGF	-0.12	0.17	-9999	-0.47	54	54
THBS1	-0.011	0.11	-9999	-0.49	17	17
integrin-mediated signaling pathway	-0.1	0.2	-9999	-0.5	54	54
positive regulation of MAPKKK cascade	-0.098	0.18	-9999	-0.47	52	52
Syndecan-4/TACI	-0.11	0.2	-9999	-0.51	53	53
CXCR4	0.008	0.049	-9999	-0.54	3	3
cell adhesion	0.002	0.074	-9999	-0.25	20	20
Syndecan-4/Dynamin	-0.088	0.19	-9999	-0.5	49	49
Syndecan-4/TSP1	-0.099	0.2	-9999	-0.51	51	51
Syndecan-4/GIPC	-0.088	0.19	-9999	-0.5	49	49
Syndecan-4/RANTES	-0.11	0.21	-9999	-0.52	54	54
ITGB1	0.012	0	-9999	-10000	0	0
LAMA1	-0.14	0.24	-9999	-0.52	102	102
LAMA3	-0.027	0.14	-9999	-0.53	27	27
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	0.008	0.11	-9999	-0.48	17	17
Syndecan-4/alpha-Actinin	-0.088	0.19	-9999	-0.5	49	49
TFPI	-0.033	0.14	-9999	-0.48	34	34
F2	-0.034	0.13	-9999	-0.45	33	33
alpha5/beta1 Integrin	0.016	0.027	-9999	-0.35	2	2
positive regulation of cell adhesion	-0.16	0.23	-9999	-0.52	77	77
ACTN1	0.012	0	-9999	-10000	0	0
TNC	-0.033	0.15	-9999	-0.51	32	32
Syndecan-4/CXCL12	-0.11	0.2	-9999	-0.51	53	53
FGF6	-0.001	0.033	-9999	-0.45	2	2
RHOA	0.012	0	-9999	-10000	0	0
CXCL12	-0.034	0.15	-9999	-0.51	33	33
TNFRSF13B	-0.034	0.14	-9999	-0.46	34	34
FGF2	-0.027	0.14	-9999	-0.5	28	28
FGFR1	0.002	0.073	-9999	-0.53	7	7
Syndecan-4/PI-4-5-P2	-0.095	0.19	-9999	-0.5	49	49
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.018	0.12	-9999	-0.46	25	25
cell migration	-0.008	0.016	-9999	-10000	0	0
PRKCD	0.011	0.039	-9999	-0.5	2	2
vasculogenesis	-0.095	0.19	-9999	-0.49	51	51
SDC4	-0.1	0.2	-9999	-0.53	49	49
Syndecan-4/Tenascin C	-0.11	0.21	-9999	-0.53	54	54
Syndecan-4/PI-4-5-P2/PKC alpha	-0.023	0.031	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.088	0.19	-9999	-0.5	49	49
MMP9	-0.075	0.2	-9999	-0.5	64	64
Rac1/GTP	0.002	0.076	-9999	-0.26	20	20
cytoskeleton organization	-0.085	0.18	-9999	-0.48	49	49
GIPC1	0.012	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.11	0.21	-9999	-0.51	53	53

×

HIF-1-alpha transcription factor network

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
PKM2	-0.2	0.45	-9999	-1.1	41	41
HDAC7	0.012	0.024	-9999	-0.45	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.2	0.31	-9999	-0.85	33	33
SMAD4	0.012	0.029	-9999	-0.54	1	1
ID2	-0.21	0.45	-9999	-1.1	39	39
AP1	-0.005	0.092	-9999	-0.34	25	25
ABCG2	-0.22	0.47	-9999	-1.2	40	40
HIF1A	-0.018	0.072	-9999	-10000	0	0
TFF3	-0.32	0.51	-9999	-1.1	71	71
GATA2	-0.059	0.18	-9999	-0.53	49	49
AKT1	-0.026	0.09	-9999	-0.63	1	1
response to hypoxia	-0.04	0.087	-9999	-0.24	4	4
MCL1	-0.2	0.45	-9999	-1.1	38	38
NDRG1	-0.22	0.46	-9999	-1.1	39	39
SERPINE1	-0.22	0.46	-9999	-1.1	42	42
FECH	-0.2	0.45	-9999	-1.1	39	39
FURIN	-0.21	0.45	-9999	-1.1	41	41
NCOA2	-0.007	0.1	-9999	-0.52	14	14
EP300	-0.021	0.12	-9999	-0.33	10	10
HMOX1	-0.21	0.46	-9999	-1.1	40	40
BHLHE40	-0.21	0.45	-9999	-1.1	38	38
BHLHE41	-0.23	0.48	-9999	-1.1	51	51
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.018	0.07	-9999	-0.38	2	2
ENG	0.017	0.095	-9999	-0.56	1	1
JUN	0.01	0.037	-9999	-0.49	2	2
RORA	-0.21	0.45	-9999	-1.1	40	40
ABCB1	-0.13	0.3	-9999	-1.1	26	26
TFRC	-0.21	0.45	-9999	-1.1	38	38
CXCR4	-0.21	0.45	-9999	-1.1	43	43
TF	-0.23	0.47	-9999	-1.1	48	48
CITED2	-0.21	0.45	-9999	-1.1	38	38
HIF1A/ARNT	-0.29	0.48	-9999	-1.2	49	49
LDHA	-0.029	0.048	-9999	-10000	0	0
ETS1	-0.21	0.45	-9999	-1.1	41	41
PGK1	-0.21	0.45	-9999	-1.1	39	39
NOS2	-0.24	0.47	-9999	-1.1	47	47
ITGB2	-0.21	0.46	-9999	-1.1	38	38
ALDOA	-0.21	0.45	-9999	-1.1	39	39
Cbp/p300/CITED2	-0.22	0.46	-9999	-1.2	36	36
FOS	-0.019	0.12	-9999	-0.47	24	24
HK2	-0.21	0.45	-9999	-1.1	38	38
SP1	0.016	0.017	-9999	-10000	0	0
GCK	-0.12	0.3	-9999	-0.79	38	38
HK1	-0.2	0.45	-9999	-1.1	41	41
NPM1	-0.2	0.45	-9999	-1.1	38	38
EGLN1	-0.2	0.45	-9999	-1.1	38	38
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.2	0.45	-9999	-1.1	38	38
SMAD3	0.013	0.001	-9999	-10000	0	0
EDN1	-0.086	0.29	-9999	-1	20	20
IGFBP1	-0.23	0.46	-9999	-1.1	40	40
VEGFA	-0.11	0.33	-9999	-0.8	21	21
HIF1A/JAB1	-0.013	0.034	-9999	-10000	0	0
CP	-0.26	0.49	-9999	-1.1	58	58
CXCL12	-0.23	0.47	-9999	-1.1	44	44
COPS5	0.012	0.004	-9999	-10000	0	0
SMAD3/SMAD4	0.019	0.021	-9999	-0.38	1	1
BNIP3	-0.21	0.45	-9999	-1.1	41	41
EGLN3	-0.22	0.46	-9999	-1.1	44	44
CA9	-0.27	0.5	-9999	-1.1	58	58
TERT	-0.25	0.48	-9999	-1.1	50	50
ENO1	-0.2	0.45	-9999	-1.1	41	41
PFKL	-0.2	0.45	-9999	-1.1	38	38
NCOA1	0.012	0.002	-9999	-10000	0	0
ADM	-0.22	0.46	-9999	-1.1	41	41
ARNT	-0.018	0.072	-9999	-10000	0	0
HNF4A	-0.16	0.24	-9999	-0.5	117	117
ADFP	-0.23	0.44	-9999	-1.1	46	46
SLC2A1	-0.11	0.33	-9999	-0.84	19	19
LEP	-0.22	0.45	-9999	-1.1	38	38
HIF1A/ARNT/Cbp/p300	-0.16	0.36	-9999	-0.88	32	32
EPO	-0.1	0.28	-9999	-0.87	8	8
CREBBP	-0.021	0.12	-9999	-0.33	9	9
HIF1A/ARNT/Cbp/p300/HDAC7	-0.19	0.31	-9999	-0.86	33	33
PFKFB3	-0.22	0.46	-9999	-1.1	42	42
NT5E	-0.25	0.49	-9999	-1.1	58	58

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.043	0.14	-9999	-0.39	41	41
alphaM/beta2 Integrin/GPIbA	-0.021	0.12	-9999	-0.35	34	34
alphaM/beta2 Integrin/proMMP-9	-0.064	0.17	-9999	-0.36	77	77
PLAUR	0.007	0.053	-9999	-0.5	4	4
HMGB1	0.001	0.044	-9999	-0.54	2	2
alphaM/beta2 Integrin/Talin	-0.011	0.1	-9999	-0.36	25	25
AGER	-0.008	0.081	-9999	-0.51	9	9
RAP1A	0.012	0	-9999	-10000	0	0
SELPLG	0.004	0.064	-9999	-0.5	6	6
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.034	0.14	-9999	-0.5	15	15
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.076	0.2	-9999	-0.5	64	64
CYR61	0.001	0.075	-9999	-0.47	9	9
TLN1	0.012	0	-9999	-10000	0	0
Rap1/GTP	-0.091	0.12	-9999	-0.4	27	27
RHOA	0.012	0	-9999	-10000	0	0
P-selectin oligomer	-0.055	0.18	-9999	-0.52	47	47
MYH2	-0.12	0.16	-9999	-0.4	48	48
MST1R	-0.041	0.16	-9999	-0.53	36	36
leukocyte activation during inflammatory response	-0.069	0.14	-9999	-0.32	57	57
APOB	-0.009	0.085	-9999	-0.45	13	13
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.04	0.16	-9999	-0.5	38	38
JAM3	0.007	0.05	-9999	-0.47	4	4
GP1BA	-0.004	0.086	-9999	-0.49	11	11
alphaM/beta2 Integrin/CTGF	-0.018	0.11	-9999	-0.35	33	33
alphaM/beta2 Integrin	-0.1	0.15	-9999	-0.38	50	50
JAM3 homodimer	0.007	0.05	-9999	-0.47	4	4
ICAM2	0.007	0.055	-9999	-0.52	4	4
ICAM1	0.004	0.062	-9999	-0.48	6	6
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.1	0.15	-9999	-0.38	50	50
cell adhesion	-0.021	0.12	-9999	-0.35	34	34
NFKB1	-0.054	0.18	-9999	-0.52	22	22
THY1	0.006	0.056	-9999	-0.47	5	5
RhoA/GDP	0.009	0	-9999	-10000	0	0
Lipoprotein(a)	-0.055	0.13	-9999	-0.3	79	79
alphaM/beta2 Integrin/LRP/tPA	-0.022	0.12	-9999	-0.37	30	30
IL6	-0.073	0.23	-9999	-0.67	30	30
ITGB2	-0.012	0.091	-9999	-0.5	12	12
elevation of cytosolic calcium ion concentration	-0.015	0.12	-9999	-0.36	29	29
alphaM/beta2 Integrin/JAM2/JAM3	-0.022	0.12	-9999	-0.37	33	33
JAM2	-0.021	0.12	-9999	-0.5	24	24
alphaM/beta2 Integrin/ICAM1	-0.036	0.15	-9999	-0.44	24	24
alphaM/beta2 Integrin/uPA/Plg	-0.061	0.15	-9999	-0.35	50	50
RhoA/GTP	-0.12	0.16	-9999	-0.42	45	45
positive regulation of phagocytosis	-0.09	0.14	-9999	-0.46	32	32
Ron/MSP	-0.036	0.14	-9999	-0.37	51	51
alphaM/beta2 Integrin/uPAR/uPA	-0.014	0.12	-9999	-0.37	29	29
alphaM/beta2 Integrin/uPAR	-0.014	0.11	-9999	-0.38	27	27
PLAU	-0.005	0.093	-9999	-0.49	13	13
PLAT	-0.017	0.12	-9999	-0.49	22	22
actin filament polymerization	-0.11	0.15	-9999	-0.39	48	48
MST1	-0.009	0.1	-9999	-0.48	16	16
alphaM/beta2 Integrin/lipoprotein(a)	-0.062	0.14	-9999	-0.33	57	57
TNF	-0.091	0.26	-9999	-0.7	42	42
RAP1B	0.012	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.022	0.12	-9999	-0.35	37	37
fibrinolysis	-0.062	0.15	-9999	-0.34	50	50
HCK	-0.012	0.11	-9999	-0.51	17	17
dendritic cell antigen processing and presentation	-0.1	0.15	-9999	-0.38	50	50
VTN	-0.009	0.095	-9999	-0.46	16	16
alphaM/beta2 Integrin/CYR61	-0.018	0.11	-9999	-0.35	33	33
LPA	-0.083	0.19	-9999	-0.47	71	71
LRP1	0.005	0.06	-9999	-0.47	6	6
cell migration	-0.08	0.18	-9999	-0.39	76	76
FN1	-0.02	0.12	-9999	-0.47	25	25
alphaM/beta2 Integrin/Thy1	-0.015	0.11	-9999	-0.34	30	30
MPO	-0.044	0.16	-9999	-0.49	41	41
KNG1	-0.017	0.1	-9999	-0.45	19	19
RAP1/GDP	0.017	0	-9999	-10000	0	0
ROCK1	-0.11	0.15	-9999	-0.39	45	45
ELA2	0	0	-9999	-10000	0	0
PLG	-0.079	0.19	-9999	-0.47	69	69
CTGF	0	0.078	-9999	-0.49	9	9
alphaM/beta2 Integrin/Hck	-0.025	0.13	-9999	-0.4	35	35
ITGAM	-0.021	0.11	-9999	-0.49	19	19
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.043	0.15	-9999	-0.36	52	52
HP	-0.25	0.26	-9999	-0.5	191	191
leukocyte adhesion	-0.067	0.12	-9999	-0.42	28	28
SELP	-0.055	0.18	-9999	-0.52	47	47

×

Glucocorticoid receptor regulatory network

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
PCK2	0.029	0.079	0.32	5	-10000	0	5
SMARCC2	0.013	0.008	-10000	0	-10000	0	0
SMARCC1	0.013	0.008	-10000	0	-10000	0	0
TBX21	-0.11	0.23	-10000	0	-0.68	41	41
SUMO2	0.014	0.012	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.037	-10000	0	-0.44	2	2
FKBP4	0.012	0	-10000	0	-10000	0	0
FKBP5	-0.016	0.12	-10000	0	-0.49	21	21
GR alpha/HSP90/FKBP51/HSP90	0.076	0.13	0.3	33	-0.32	10	43
PRL	-0.079	0.15	-10000	0	-0.56	5	5
cortisol/GR alpha (dimer)/TIF2	0.2	0.24	0.54	84	-0.38	5	89
RELA	-0.019	0.071	-10000	0	-10000	0	0
FGG	0.16	0.19	0.49	48	-0.42	4	52
GR beta/TIF2	0.083	0.14	0.32	38	-0.37	14	52
IFNG	-0.28	0.32	-10000	0	-0.77	80	80
apoptosis	0.036	0.21	0.53	28	-0.64	6	34
CREB1	0.005	0.04	-10000	0	-10000	0	0
histone acetylation	-0.015	0.14	0.31	8	-0.37	18	26
BGLAP	-0.061	0.14	-10000	0	-0.49	15	15
GR/PKAc	0.086	0.11	0.28	32	-0.32	5	37
NF kappa B1 p50/RelA	-0.03	0.13	-10000	0	-0.4	11	11
SMARCD1	0.013	0.008	-10000	0	-10000	0	0
MDM2	0.084	0.089	0.24	53	-0.27	2	55
GATA3	-0.028	0.14	-10000	0	-0.48	32	32
AKT1	0.004	0.024	-10000	0	-0.46	1	1
CSF2	-0.05	0.12	-10000	0	-0.62	3	3
GSK3B	0.014	0.012	-10000	0	-10000	0	0
NR1I3	0.026	0.27	0.53	24	-0.87	19	43
CSN2	0.14	0.16	0.4	41	-0.35	4	45
BRG1/BAF155/BAF170/BAF60A	0.033	0.035	-10000	0	-0.28	2	2
NFATC1	0.003	0.081	-10000	0	-0.54	8	8
POU2F1	-0.002	0.078	-10000	0	-0.46	9	9
CDKN1A	-0.046	0.3	-10000	0	-1.5	15	15
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.002	0.012	-10000	0	-10000	0	0
SFN	-0.056	0.18	-10000	0	-0.51	49	49
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.039	0.15	0.28	28	-0.35	15	43
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.04	0.22	0.51	24	-0.73	11	35
JUN	-0.18	0.19	-10000	0	-0.48	66	66
IL4	-0.078	0.14	-10000	0	-0.5	15	15
CDK5R1	0.002	0.074	-10000	0	-0.49	8	8
PRKACA	0.012	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.15	0.21	0.22	17	-0.49	73	90
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.083	0.12	0.29	32	-0.32	6	38
cortisol/GR alpha (monomer)	0.25	0.28	0.64	88	-0.45	2	90
NCOA2	-0.008	0.1	-10000	0	-0.52	14	14
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.081	0.13	-10000	0	-0.52	24	24
AP-1/NFAT1-c-4	-0.31	0.32	-10000	0	-0.72	107	107
AFP	-0.12	0.15	-10000	0	-0.61	7	7
SUV420H1	0.012	0	-10000	0	-10000	0	0
IRF1	0.14	0.14	0.44	27	-10000	0	27
TP53	-0.009	0.15	-10000	0	-0.53	26	26
PPP5C	0.012	0	-10000	0	-10000	0	0
KRT17	-0.38	0.46	-10000	0	-0.99	108	108
KRT14	-0.3	0.45	-10000	0	-1.2	66	66
TBP	0.019	0.018	-10000	0	-0.3	1	1
CREBBP	0.068	0.1	0.29	34	-10000	0	34
HDAC1	0.012	0.002	-10000	0	-10000	0	0
HDAC2	0.012	0.006	-10000	0	-10000	0	0
AP-1	-0.31	0.32	-10000	0	-0.72	110	110
MAPK14	0.014	0.01	-10000	0	-10000	0	0
MAPK10	-0.04	0.16	-10000	0	-0.52	38	38
MAPK11	0.01	0.046	-10000	0	-0.48	3	3
KRT5	-0.47	0.51	-10000	0	-1.1	128	128
interleukin-1 receptor activity	0	0.006	-10000	0	-10000	0	0
NCOA1	0.015	0.001	-10000	0	-10000	0	0
STAT1	0.016	0.037	-10000	0	-0.44	2	2
CGA	-0.089	0.16	-10000	0	-0.48	31	31
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.13	0.14	0.38	52	-10000	0	52
MAPK3	0.013	0.027	-10000	0	-0.45	1	1
MAPK1	0.013	0.027	-10000	0	-0.46	1	1
ICAM1	-0.12	0.21	-10000	0	-0.69	24	24
NFKB1	-0.019	0.071	-10000	0	-10000	0	0
MAPK8	-0.14	0.17	-10000	0	-0.45	53	53
MAPK9	0.014	0.01	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.027	0.21	0.54	28	-0.67	6	34
BAX	-0.002	0.1	-10000	0	-0.49	1	1
POMC	-0.21	0.36	-10000	0	-1.2	33	33
EP300	0.068	0.1	0.28	39	-10000	0	39
cortisol/GR alpha (dimer)/p53	0.2	0.25	0.55	83	-0.48	4	87
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.07	0.22	20	-0.24	2	22
SGK1	0.098	0.2	-10000	0	-1.3	4	4
IL13	-0.2	0.22	-10000	0	-0.67	39	39
IL6	-0.16	0.29	-10000	0	-0.8	43	43
PRKACG	0.001	0.034	-10000	0	-0.45	2	2
IL5	-0.18	0.18	-10000	0	-0.63	24	24
IL2	-0.25	0.26	-10000	0	-0.66	69	69
CDK5	0.013	0.005	-10000	0	-10000	0	0
PRKACB	0.003	0.07	-10000	0	-0.54	6	6
HSP90AA1	0.012	0	-10000	0	-10000	0	0
IL8	-0.18	0.33	-10000	0	-0.89	53	53
CDK5R1/CDK5	0.012	0.055	-10000	0	-0.34	8	8
NF kappa B1 p50/RelA/PKAc	-0.007	0.1	-10000	0	-0.37	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.21	0.51	86	-10000	0	86
SMARCA4	0.01	0.041	-10000	0	-0.54	2	2
chromatin remodeling	0.14	0.14	0.38	57	-10000	0	57
NF kappa B1 p50/RelA/Cbp	0.044	0.15	0.33	18	-0.6	1	19
JUN (dimer)	-0.18	0.19	-10000	0	-0.48	66	66
YWHAH	0.012	0	-10000	0	-10000	0	0
VIPR1	-0.12	0.25	-10000	0	-0.64	55	55
NR3C1	0.14	0.18	0.45	56	-0.46	5	61
NR4A1	-0.051	0.16	-10000	0	-0.48	41	41
TIF2/SUV420H1	0.004	0.074	-10000	0	-0.37	14	14
MAPKKK cascade	0.036	0.21	0.53	28	-0.64	6	34
cortisol/GR alpha (dimer)/Src-1	0.22	0.23	0.54	89	-0.38	2	91
PBX1	0.001	0.074	-10000	0	-0.54	6	6
POU1F1	-0.003	0.044	-10000	0	-0.45	2	2
SELE	-0.18	0.32	-10000	0	-0.84	55	55
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.14	0.38	57	-10000	0	57
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.21	0.51	86	-10000	0	86
mol:cortisol	0.14	0.16	0.36	93	-10000	0	93
MMP1	-0.24	0.41	-10000	0	-0.95	74	74

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.007	0.17	0.27	27	-0.51	18	45
PTK2B	0.009	0.04	-10000	0	-0.54	2	2
mol:Ca2+	-0.02	0.23	-10000	0	-0.79	20	20
EDN1	-0.001	0.14	-10000	0	-0.46	21	21
EDN3	-0.24	0.26	-10000	0	-0.5	178	178
EDN2	-0.06	0.18	-10000	0	-0.49	53	53
HRAS/GDP	-0.033	0.17	-10000	0	-0.49	24	24
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0	0.15	-10000	0	-0.45	21	21
ADCY4	-0.01	0.15	-10000	0	-0.45	24	24
ADCY5	-0.047	0.18	-10000	0	-0.46	35	35
ADCY6	-0.006	0.15	-10000	0	-0.46	23	23
ADCY7	-0.007	0.15	-10000	0	-0.46	22	22
ADCY1	-0.052	0.18	-10000	0	-0.44	38	38
ADCY2	-0.044	0.2	-10000	0	-0.49	41	41
ADCY3	-0.005	0.15	-10000	0	-0.45	22	22
ADCY8	-0.022	0.16	-10000	0	-0.46	27	27
ADCY9	-0.018	0.17	-10000	0	-0.48	30	30
arachidonic acid secretion	-0.043	0.18	-10000	0	-0.46	34	34
ETB receptor/Endothelin-1/Gq/GTP	-0.009	0.13	-10000	0	-0.37	23	23
GNAO1	-0.014	0.11	-10000	0	-0.47	20	20
HRAS	0.011	0.024	-10000	0	-0.45	1	1
ETA receptor/Endothelin-1/G12/GTP	0.028	0.18	0.32	46	-0.48	17	63
ETA receptor/Endothelin-1/Gs/GTP	0.006	0.19	0.29	51	-0.46	24	75
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	-0.014	0.23	-10000	0	-0.67	29	29
EDNRB	-0.024	0.13	-10000	0	-0.49	27	27
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.005	0.19	-10000	0	-0.49	29	29
CYSLTR1	-0.013	0.22	-10000	0	-0.58	33	33
SLC9A1	-0.005	0.098	0.19	31	-0.3	12	43
mol:GDP	-0.042	0.18	-10000	0	-0.48	31	31
SLC9A3	-0.045	0.22	-10000	0	-0.59	39	39
RAF1	-0.035	0.16	-10000	0	-0.48	21	21
JUN	0.003	0.18	-10000	0	-0.7	11	11
JAK2	-0.001	0.18	0.27	27	-0.49	25	52
mol:IP3	-0.008	0.15	-10000	0	-0.48	19	19
ETA receptor/Endothelin-1	-0.004	0.22	0.36	57	-0.52	26	83
PLCB1	-0.011	0.11	-10000	0	-0.53	16	16
PLCB2	-0.001	0.083	-10000	0	-0.5	10	10
ETA receptor/Endothelin-3	-0.17	0.21	-10000	0	-0.37	173	173
FOS	-0.027	0.18	-10000	0	-0.6	16	16
Gai/GDP	-0.004	0.12	-10000	0	-0.64	8	8
CRK	0.012	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.016	0.21	-10000	0	-0.57	27	27
BCAR1	0.011	0.029	-10000	0	-0.54	1	1
PRKCB1	-0.008	0.14	-10000	0	-0.46	19	19
GNAQ	0.011	0.029	-10000	0	-0.54	1	1
GNAZ	-0.005	0.094	-10000	0	-0.52	12	12
GNAL	-0.01	0.1	-10000	0	-0.48	17	17
Gs family/GDP	-0.08	0.15	-10000	0	-0.45	38	38
ETA receptor/Endothelin-1/Gq/GTP	0.006	0.16	-10000	0	-0.51	18	18
MAPK14	-0.006	0.12	-10000	0	-0.45	13	13
TRPC6	-0.023	0.24	-10000	0	-0.85	20	20
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.095	-10000	0	-0.52	12	12
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.012	0.13	-10000	0	-0.42	18	18
ETB receptor/Endothelin-2	-0.06	0.16	-10000	0	-0.36	77	77
ETB receptor/Endothelin-3	-0.18	0.2	-10000	0	-0.37	192	192
ETB receptor/Endothelin-1	-0.016	0.15	-10000	0	-0.36	45	45
MAPK3	-0.029	0.17	-10000	0	-0.58	17	17
MAPK1	-0.029	0.18	-10000	0	-0.58	17	17
Rac1/GDP	-0.033	0.17	-10000	0	-0.48	24	24
cAMP biosynthetic process	-0.054	0.18	-10000	0	-0.45	44	44
MAPK8	-0.007	0.2	-10000	0	-0.64	19	19
SRC	0.009	0.04	-10000	0	-0.54	2	2
ETB receptor/Endothelin-1/Gi/GTP	-0.006	0.1	-10000	0	-0.31	20	20
p130Cas/CRK/Src/PYK2	-0.049	0.19	-10000	0	-0.52	28	28
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.033	0.17	-10000	0	-0.47	25	25
COL1A2	-0.018	0.23	-10000	0	-0.68	27	27
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.038	0.16	-10000	0	-0.37	62	62
mol:DAG	-0.008	0.15	-10000	0	-0.48	19	19
MAP2K2	-0.029	0.16	-10000	0	-0.48	22	22
MAP2K1	-0.029	0.16	-10000	0	-0.5	20	20
EDNRA	0.007	0.14	-10000	0	-0.53	13	13
positive regulation of muscle contraction	0.013	0.15	-10000	0	-0.48	15	15
Gq family/GDP	-0.078	0.15	-10000	0	-0.53	25	25
HRAS/GTP	-0.042	0.16	-10000	0	-0.46	26	26
PRKCH	-0.004	0.15	-10000	0	-0.51	17	17
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	-0.015	0.16	-10000	0	-0.46	25	25
PRKCB	-0.02	0.17	-10000	0	-0.47	29	29
PRKCE	-0.002	0.14	-10000	0	-0.49	16	16
PRKCD	-0.004	0.14	-10000	0	-0.48	17	17
PRKCG	-0.077	0.19	-10000	0	-0.45	40	40
regulation of vascular smooth muscle contraction	-0.032	0.2	-10000	0	-0.72	15	15
PRKCQ	-0.05	0.18	-10000	0	-0.46	36	36
PLA2G4A	-0.048	0.19	-10000	0	-0.5	34	34
GNA14	-0.002	0.09	-10000	0	-0.54	10	10
GNA15	-0.004	0.093	-10000	0	-0.51	12	12
GNA12	0.012	0	-10000	0	-10000	0	0
GNA11	0	0.082	-10000	0	-0.52	9	9
Rac1/GTP	0.028	0.18	0.31	52	-0.48	17	69
MMP1	-0.12	0.31	0.31	1	-0.65	83	84

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.023	0.1	-10000	0	-0.47	10	10
NFATC2	-0.061	0.22	-10000	0	-0.6	32	32
NFATC3	-0.019	0.071	-10000	0	-0.3	1	1
CD40LG	-0.21	0.38	-10000	0	-0.97	52	52
ITCH	-0.01	0.095	-10000	0	-0.61	1	1
CBLB	-0.008	0.09	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.23	0.42	-10000	0	-1.1	60	60
JUNB	0.006	0.057	-10000	0	-0.54	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.024	0.11	-10000	0	-0.28	20	20
T cell anergy	-0.043	0.13	-10000	0	-0.37	25	25
TLE4	-0.035	0.18	-10000	0	-0.6	19	19
Jun/NFAT1-c-4/p21SNFT	-0.14	0.34	-10000	0	-0.98	33	33
AP-1/NFAT1-c-4	-0.22	0.42	-10000	0	-1.1	48	48
IKZF1	-0.044	0.21	-10000	0	-0.68	25	25
T-helper 2 cell differentiation	-0.077	0.23	-10000	0	-0.76	24	24
AP-1/NFAT1	-0.061	0.17	-10000	0	-0.46	30	30
CALM1	-0.009	0.062	-10000	0	-10000	0	0
EGR2	-0.1	0.33	-10000	0	-1.2	18	18
EGR3	-0.13	0.38	-10000	0	-1.2	32	32
NFAT1/FOXP3	-0.066	0.21	-10000	0	-0.58	29	29
EGR1	-0.017	0.11	-10000	0	-0.49	19	19
JUN	-0.004	0.045	-10000	0	-0.52	2	2
EGR4	-0.017	0.1	-10000	0	-0.46	18	18
mol:Ca2+	-0.022	0.065	-10000	0	-10000	0	0
GBP3	-0.061	0.24	-10000	0	-0.72	34	34
FOSL1	-0.024	0.13	-10000	0	-0.49	27	27
NFAT1-c-4/MAF/IRF4	-0.15	0.34	-10000	0	-0.98	38	38
DGKA	-0.027	0.16	-10000	0	-0.56	14	14
CREM	0.012	0.003	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.18	0.35	-10000	0	-0.99	39	39
CTLA4	-0.11	0.28	-10000	0	-0.66	62	62
NFAT1-c-4 (dimer)/EGR1	-0.14	0.34	-10000	0	-0.95	39	39
NFAT1-c-4 (dimer)/EGR4	-0.14	0.34	-10000	0	-0.96	36	36
FOS	-0.032	0.12	-10000	0	-0.48	24	24
IFNG	-0.14	0.31	-10000	0	-0.87	42	42
T cell activation	-0.084	0.2	-10000	0	-0.66	11	11
MAF	0	0.076	-10000	0	-0.48	9	9
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.087	0.28	0.91	24	-10000	0	24
TNF	-0.18	0.36	-10000	0	-0.92	49	49
FASLG	-0.22	0.51	-10000	0	-1.4	47	47
TBX21	-0.038	0.15	-10000	0	-0.51	34	34
BATF3	-0.005	0.092	-10000	0	-0.48	13	13
PRKCQ	-0.086	0.21	-10000	0	-0.53	66	66
PTPN1	-0.026	0.16	-10000	0	-0.53	15	15
NFAT1-c-4/ICER1	-0.12	0.32	-10000	0	-0.96	33	33
GATA3	-0.029	0.14	-10000	0	-0.48	32	32
T-helper 1 cell differentiation	-0.13	0.31	-10000	0	-0.84	43	43
IL2RA	-0.19	0.31	-10000	0	-0.91	45	45
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.026	0.16	-10000	0	-0.54	14	14
E2F1	0.009	0.067	-10000	0	-0.47	7	7
PPARG	-0.096	0.21	-10000	0	-0.51	76	76
SLC3A2	-0.026	0.16	-10000	0	-0.53	15	15
IRF4	-0.08	0.2	-10000	0	-0.49	68	68
PTGS2	-0.25	0.4	-10000	0	-0.95	63	63
CSF2	-0.2	0.36	-10000	0	-0.95	44	44
JunB/Fra1/NFAT1-c-4	-0.12	0.32	-10000	0	-0.97	32	32
IL4	-0.08	0.24	-10000	0	-0.8	24	24
IL5	-0.2	0.35	-10000	0	-0.93	46	46
IL2	-0.085	0.2	-10000	0	-0.67	11	11
IL3	-0.047	0.056	-10000	0	-10000	0	0
RNF128	-0.071	0.21	-10000	0	-0.45	82	82
NFATC1	-0.088	0.28	-10000	0	-0.92	24	24
CDK4	0.06	0.16	0.64	7	-10000	0	7
PTPRK	-0.027	0.16	-10000	0	-0.56	15	15
IL8	-0.22	0.39	-10000	0	-0.97	57	57
POU2F1	0.001	0.071	-10000	0	-0.45	9	9

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.047	0.13	-10000	0	-0.35	32	32
IKBKB	-0.021	0.072	-10000	0	-0.26	4	4
AKT1	-0.057	0.1	0.2	1	-0.24	50	51
IKBKG	-0.021	0.076	-10000	0	-0.26	7	7
CALM1	-0.041	0.12	0.24	1	-0.4	21	22
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
MAP3K1	-0.082	0.19	-10000	0	-0.47	52	52
MAP3K7	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	-0.049	0.13	0.21	5	-0.41	23	28
DOK1	0.012	0	-10000	0	-10000	0	0
AP-1	-0.02	0.08	0.15	2	-0.23	17	19
LYN	0.008	0.049	-10000	0	-0.54	3	3
BLNK	-0.006	0.097	-10000	0	-0.54	12	12
SHC1	0.012	0	-10000	0	-10000	0	0
BCR complex	-0.11	0.2	-10000	0	-0.4	109	109
CD22	-0.15	0.22	-10000	0	-0.53	66	66
CAMK2G	-0.033	0.11	0.24	1	-0.43	14	15
CSNK2A1	0.012	0	-10000	0	-10000	0	0
INPP5D	-0.002	0.088	-10000	0	-0.53	10	10
SHC/GRB2/SOS1	-0.083	0.14	-10000	0	-0.42	31	31
GO:0007205	-0.05	0.13	0.21	5	-0.42	23	28
SYK	0.001	0.079	-10000	0	-0.53	8	8
ELK1	-0.042	0.12	0.24	1	-0.41	21	22
NFATC1	-0.076	0.18	-10000	0	-0.42	53	53
B-cell antigen/BCR complex	-0.11	0.2	-10000	0	-0.4	109	109
PAG1/CSK	0.008	0.061	-10000	0	-0.36	10	10
NFKBIB	0.001	0.027	0.071	1	-10000	0	1
HRAS	-0.042	0.12	0.22	1	-0.38	24	25
NFKBIA	0.001	0.026	0.071	1	-10000	0	1
NF-kappa-B/RelA/I kappa B beta	0.007	0.022	-10000	0	-10000	0	0
RasGAP/Csk	-0.07	0.17	-10000	0	-0.48	29	29
mol:GDP	-0.047	0.12	0.23	2	-0.4	23	25
PTEN	0.002	0.075	-10000	0	-0.54	7	7
CD79B	-0.043	0.16	-10000	0	-0.48	41	41
NF-kappa-B/RelA/I kappa B alpha	0.007	0.022	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.11	0.2	-10000	0	-0.47	69	69
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
mol:IP3	-0.051	0.13	0.21	5	-0.43	23	28
CSK	0.012	0	-10000	0	-10000	0	0
FOS	-0.047	0.13	0.24	1	-0.46	18	19
CHUK	-0.021	0.076	-10000	0	-0.26	6	6
IBTK	0.009	0.04	-10000	0	-0.54	2	2
CARD11/BCL10/MALT1/TAK1	-0.07	0.12	-10000	0	-0.39	32	32
PTPN6	-0.13	0.22	-10000	0	-0.55	56	56
RELA	0.012	0	-10000	0	-10000	0	0
BCL2A1	0.004	0.028	-10000	0	-0.097	12	12
VAV2	-0.12	0.23	-10000	0	-0.51	69	69
ubiquitin-dependent protein catabolic process	0.005	0.026	0.074	1	-10000	0	1
BTK	-0.029	0.18	0.34	6	-1	11	17
CD19	-0.14	0.22	-10000	0	-0.53	70	70
MAP4K1	-0.006	0.095	-10000	0	-0.48	14	14
CD72	0	0.076	-10000	0	-0.48	9	9
PAG1	-0.002	0.084	-10000	0	-0.5	10	10
MAPK14	-0.064	0.16	-10000	0	-0.42	41	41
SH3BP5	-0.006	0.098	-10000	0	-0.54	12	12
PIK3AP1	-0.052	0.15	0.22	4	-0.46	26	30
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.066	0.17	-10000	0	-0.42	53	53
RAF1	-0.034	0.12	0.22	1	-0.41	15	16
RasGAP/p62DOK/SHIP	-0.072	0.17	-10000	0	-0.49	32	32
CD79A	-0.11	0.22	-10000	0	-0.48	91	91
re-entry into mitotic cell cycle	-0.02	0.08	0.15	2	-0.23	18	20
RASA1	0.012	0	-10000	0	-10000	0	0
MAPK3	-0.018	0.1	0.21	1	-0.39	10	11
MAPK1	-0.018	0.1	0.21	1	-0.38	11	12
CD72/SHP1	-0.12	0.22	-10000	0	-0.53	58	58
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	-0.065	0.16	-10000	0	-0.42	44	44
actin cytoskeleton organization	-0.095	0.2	-10000	0	-0.48	54	54
NF-kappa-B/RelA	0.018	0.042	0.14	1	-10000	0	1
Calcineurin	-0.032	0.11	-10000	0	-0.41	15	15
PI3K	-0.15	0.18	-10000	0	-0.46	77	77
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.053	0.14	0.23	4	-0.44	27	31
SOS1	0.012	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.26	-10000	0	-0.74	43	43
DAPP1	-0.14	0.29	-10000	0	-0.88	38	38
cytokine secretion	-0.07	0.16	-10000	0	-0.39	53	53
mol:DAG	-0.051	0.13	0.21	5	-0.43	23	28
PLCG2	0	0.076	-10000	0	-0.48	9	9
MAP2K1	-0.026	0.11	0.21	1	-0.41	12	13
B-cell antigen/BCR complex/FcgammaRIIB	-0.097	0.19	-10000	0	-0.36	119	119
mol:PI-3-4-5-P3	-0.11	0.13	0.21	2	-0.32	76	78
ETS1	-0.025	0.1	0.23	1	-0.38	15	16
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.074	0.17	-10000	0	-0.48	32	32
B-cell antigen/BCR complex/LYN	-0.1	0.18	-10000	0	-0.41	74	74
MALT1	0.006	0.053	-10000	0	-0.45	5	5
TRAF6	0.012	0	-10000	0	-10000	0	0
RAC1	-0.1	0.21	-10000	0	-0.52	54	54
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.21	-10000	0	-0.52	62	62
CARD11	-0.071	0.15	-10000	0	-0.4	48	48
FCGR2B	-0.015	0.12	-10000	0	-0.52	19	19
PPP3CA	0.006	0.057	-10000	0	-0.54	4	4
BCL10	0.012	0	-10000	0	-10000	0	0
IKK complex	-0.004	0.034	-10000	0	-10000	0	0
PTPRC	-0.032	0.15	-10000	0	-0.51	31	31
PDPK1	-0.058	0.1	0.19	1	-0.24	45	46
PPP3CB	0.012	0	-10000	0	-10000	0	0
PPP3CC	0	0.08	-10000	0	-0.54	8	8
POU2F2	0.005	0.025	-10000	0	-0.094	6	6

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.012	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.028	0.095	-10000	0	-0.32	12	12
NT3 (dimer)/TRKC	-0.1	0.2	-10000	0	-0.4	106	106
NT3 (dimer)/TRKB	-0.13	0.21	-10000	0	-0.35	155	155
SHC/Grb2/SOS1/GAB1/PI3K	0.017	0.06	-10000	0	-10000	0	0
RAPGEF1	0.012	0	-10000	0	-10000	0	0
BDNF	-0.087	0.2	-10000	0	-0.48	74	74
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
DYNLT1	0.012	0	-10000	0	-10000	0	0
NTRK1	-0.043	0.16	-10000	0	-0.5	40	40
NTRK2	-0.076	0.19	-10000	0	-0.49	65	65
NTRK3	-0.079	0.2	-10000	0	-0.5	66	66
NT-4/5 (dimer)/TRKB	-0.13	0.2	-10000	0	-0.34	159	159
neuron apoptosis	0.12	0.19	0.43	68	-10000	0	68
SHC 2-3/Grb2	-0.13	0.21	-10000	0	-0.47	68	68
SHC1	0.012	0	-10000	0	-10000	0	0
SHC2	-0.12	0.18	0.2	3	-0.47	48	51
SHC3	-0.14	0.22	0.2	3	-0.53	61	64
STAT3 (dimer)	0.003	0.073	-10000	0	-0.34	15	15
NT3 (dimer)/TRKA	-0.11	0.2	-10000	0	-0.36	131	131
RIN/GDP	-0.02	0.076	-10000	0	-0.25	5	5
GIPC1	0.012	0	-10000	0	-10000	0	0
KRAS	0.012	0	-10000	0	-10000	0	0
DNAJA3	-0.069	0.15	0.23	4	-0.36	52	56
RIN/GTP	0.002	0.004	-10000	0	-10000	0	0
CCND1	-0.009	0.16	-10000	0	-0.71	18	18
MAGED1	0.002	0.075	-10000	0	-0.54	7	7
PTPN11	0.012	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.068	0.18	-10000	0	-0.49	57	57
SHC/GRB2/SOS1	0.025	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.064	0.17	-10000	0	-0.34	90	90
TRKA/NEDD4-2	-0.023	0.12	-10000	0	-0.35	41	41
ELMO1	0.007	0.053	-10000	0	-0.5	4	4
RhoG/GTP/ELMO1/DOCK1	0.013	0.032	-10000	0	-0.3	4	4
NGF	-0.045	0.16	-10000	0	-0.5	41	41
HRAS	0.011	0.024	-10000	0	-0.45	1	1
DOCK1	0.012	0	-10000	0	-10000	0	0
GAB2	0.01	0.034	-10000	0	-0.45	2	2
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.011	0.029	-10000	0	-0.54	1	1
FRS2	0.012	0	-10000	0	-10000	0	0
DNM1	-0.012	0.11	-10000	0	-0.48	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.012	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.07	0.15	0.22	4	-0.36	54	58
mol:GDP	-0.031	0.11	-10000	0	-0.34	10	10
NGF (dimer)	-0.045	0.16	-10000	0	-0.5	41	41
RhoG/GDP	0.005	0.038	-10000	0	-0.36	4	4
RIT1/GDP	-0.017	0.077	-10000	0	-0.24	5	5
TIAM1	0	0.08	-10000	0	-0.54	8	8
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
BDNF (dimer)/TRKB	-0.089	0.17	-10000	0	-0.31	126	126
KIDINS220/CRKL/C3G	0.018	0	-10000	0	-10000	0	0
SHC/RasGAP	0.018	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0.024	0.018	-10000	0	-0.32	1	1
SHC/GRB2/SOS1/GAB1	0.031	0.016	-10000	0	-0.28	1	1
RIT1/GTP	0.008	0.021	-10000	0	-0.39	1	1
NT3 (dimer)	-0.067	0.18	-10000	0	-0.48	59	59
RAP1/GDP	-0.031	0.051	-10000	0	-0.24	2	2
KIDINS220/CRKL	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.087	0.2	-10000	0	-0.48	74	74
ubiquitin-dependent protein catabolic process	-0.045	0.14	-10000	0	-0.32	75	75
Schwann cell development	-0.038	0.032	-10000	0	-10000	0	0
EHD4	0.012	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.031	0.016	-10000	0	-0.28	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.034	0.017	-10000	0	-10000	0	0
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.15	0.18	-10000	0	-0.48	67	67
ABL1	0.012	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.071	-10000	0	-10000	0	0
STAT3	0.003	0.073	-10000	0	-0.34	15	15
axon guidance	-0.15	0.17	-10000	0	-0.46	67	67
MAPK3	-0.053	0.15	-10000	0	-0.34	60	60
MAPK1	-0.053	0.15	-10000	0	-0.34	60	60
CDC42/GDP	-0.016	0.076	-10000	0	-0.25	4	4
NTF3	-0.067	0.18	-10000	0	-0.48	59	59
NTF4	-0.068	0.18	-10000	0	-0.49	57	57
NGF (dimer)/TRKA/FAIM	-0.045	0.14	-10000	0	-0.32	75	75
PI3K	-0.006	0.093	-10000	0	-0.37	23	23
FRS3	0.011	0.029	-10000	0	-0.54	1	1
FAIM	0.011	0.029	-10000	0	-0.54	1	1
GAB1	0.011	0.029	-10000	0	-0.54	1	1
RASGRF1	-0.14	0.19	0.23	4	-0.41	88	92
SOS1	0.012	0	-10000	0	-10000	0	0
MCF2L	-0.092	0.18	-10000	0	-0.35	115	115
RGS19	0.009	0.04	-10000	0	-0.54	2	2
CDC42	0.012	0	-10000	0	-10000	0	0
RAS family/GTP	-0.013	0.073	-10000	0	-10000	0	0
Rac1/GDP	-0.016	0.076	-10000	0	-0.24	5	5
NGF (dimer)/TRKA/GRIT	-0.052	0.14	-10000	0	-0.33	74	74
neuron projection morphogenesis	-0.063	0.15	-10000	0	-0.5	15	15
NGF (dimer)/TRKA/NEDD4-2	-0.045	0.14	-10000	0	-0.32	75	75
MAP2K1	0.032	0.015	-10000	0	-0.26	1	1
NGFR	-0.081	0.2	-10000	0	-0.49	69	69
NGF (dimer)/TRKA/GIPC/GAIP	-0.026	0.12	-10000	0	-0.4	13	13
RAS family/GTP/PI3K	0.008	0.077	-10000	0	-0.64	2	2
FRS2 family/SHP2/GRB2/SOS1	0.036	0.015	-10000	0	-10000	0	0
NRAS	0.005	0.064	-10000	0	-0.54	5	5
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
PRKCI	0.008	0.044	-10000	0	-0.48	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.04	-10000	0	-0.54	2	2
MAPKKK cascade	-0.1	0.2	-10000	0	-0.61	45	45
RASA1	0.012	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.022	0.12	-10000	0	-0.35	40	40
SQSTM1	0.011	0.024	-10000	0	-0.45	1	1
BDNF (dimer)/TRKB/GIPC	-0.073	0.16	-10000	0	-0.35	51	51
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.028	0.13	-10000	0	-0.48	9	9
MATK	-0.022	0.13	-10000	0	-0.49	25	25
NEDD4L	0.011	0.029	-10000	0	-0.54	1	1
RAS family/GDP	-0.029	0.05	-10000	0	-0.22	3	3
NGF (dimer)/TRKA	-0.09	0.15	0.25	4	-0.34	79	83
Rac1/GTP	-0.1	0.11	-10000	0	-0.3	60	60
FRS2 family/SHP2/CRK family	0.036	0.015	-10000	0	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	-0.016	0.11	-9999	-0.35	23	23
NF kappa B1 p50/RelA/I kappa B alpha	-0.04	0.13	-9999	-0.36	20	20
AP1	-0.1	0.14	-9999	-0.46	27	27
mol:PIP3	-0.097	0.14	-9999	-0.47	28	28
AKT1	0.006	0.1	-9999	-0.39	11	11
PTK2B	-0.019	0.088	-9999	-0.27	25	25
RHOA	0.012	0.043	-9999	-10000	0	0
PIK3CB	0.012	0.001	-9999	-10000	0	0
mol:Ca2+	-0.043	0.13	-9999	-0.36	20	20
MAGI3	0.011	0.029	-9999	-0.54	1	1
RELA	0.012	0	-9999	-10000	0	0
apoptosis	-0.081	0.16	-9999	-0.33	82	82
HRAS/GDP	0.008	0.017	-9999	-0.32	1	1
positive regulation of microtubule depolymerization	-0.015	0.094	-9999	-0.33	12	12
NF kappa B1 p50/RelA	-0.086	0.14	-9999	-0.43	27	27
endothelial cell migration	-0.049	0.19	-9999	-0.5	51	51
ADCY4	-0.025	0.14	-9999	-0.45	23	23
ADCY5	-0.05	0.16	-9999	-0.46	33	33
ADCY6	-0.023	0.14	-9999	-0.45	23	23
ADCY7	-0.024	0.14	-9999	-0.45	23	23
ADCY1	-0.047	0.15	-9999	-0.5	26	26
ADCY2	-0.046	0.16	-9999	-0.45	35	35
ADCY3	-0.023	0.14	-9999	-0.45	23	23
ADCY8	-0.03	0.14	-9999	-0.45	26	26
ADCY9	-0.031	0.15	-9999	-0.45	28	28
GSK3B	-0.012	0.084	-9999	-0.3	14	14
arachidonic acid secretion	-0.019	0.13	-9999	-0.4	25	25
GNG2	-0.002	0.084	-9999	-0.48	11	11
TRIP6	0.007	0.064	-9999	-0.39	9	9
GNAO1	-0.033	0.13	-9999	-0.32	52	52
HRAS	0.011	0.024	-9999	-0.45	1	1
NFKBIA	-0.052	0.15	-9999	-0.31	74	74
GAB1	0.011	0.029	-9999	-0.54	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.14	-9999	-0.88	9	9
JUN	0.009	0.037	-9999	-0.5	2	2
LPA/LPA2/NHERF2	0.008	0.04	-9999	-0.33	3	3
TIAM1	-0.022	0.16	-9999	-1	9	9
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
mol:IP3	-0.044	0.13	-9999	-0.36	20	20
PLCB3	0.014	0.036	-9999	-0.29	3	3
FOS	-0.019	0.12	-9999	-0.47	24	24
positive regulation of mitosis	-0.019	0.13	-9999	-0.4	25	25
LPA/LPA1-2-3	-0.085	0.16	-9999	-0.34	82	82
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.011	0.029	-9999	-0.54	1	1
stress fiber formation	-0.036	0.11	-9999	-0.34	21	21
GNAZ	-0.028	0.13	-9999	-0.32	46	46
EGFR/PI3K-beta/Gab1	-0.1	0.15	-9999	-0.49	28	28
positive regulation of dendritic cell cytokine production	-0.086	0.16	-9999	-0.33	82	82
LPA/LPA2/MAGI-3	0.01	0.031	-9999	-0.32	1	1
ARHGEF1	-0.002	0.096	-9999	-0.5	5	5
GNAI2	-0.018	0.11	-9999	-0.32	35	35
GNAI3	-0.018	0.11	-9999	-0.32	35	35
GNAI1	-0.028	0.12	-9999	-0.33	46	46
LPA/LPA3	-0.097	0.17	-9999	-0.38	96	96
LPA/LPA2	0.002	0.032	-9999	-10000	0	0
LPA/LPA1	-0.031	0.13	-9999	-0.39	35	35
HB-EGF/EGFR	-0.044	0.13	-9999	-0.32	46	46
HBEGF	-0.046	0.14	-9999	-0.35	65	65
mol:DAG	-0.044	0.13	-9999	-0.36	20	20
cAMP biosynthetic process	-0.036	0.15	-9999	-0.45	27	27
NFKB1	0.012	0	-9999	-10000	0	0
SRC	0.009	0.04	-9999	-0.54	2	2
GNB1	0.012	0.001	-9999	-10000	0	0
LYN	-0.055	0.15	-9999	-0.4	25	25
GNAQ	-0.058	0.12	-9999	-0.29	71	71
LPAR2	0.012	0	-9999	-10000	0	0
LPAR3	-0.12	0.23	-9999	-0.52	96	96
LPAR1	-0.027	0.13	-9999	-0.58	18	18
IL8	-0.11	0.19	-9999	-0.46	58	58
PTK2	-0.074	0.16	-9999	-0.43	25	25
Rac1/GDP	0.009	0	-9999	-10000	0	0
CASP3	-0.082	0.16	-9999	-0.33	82	82
EGFR	-0.004	0.092	-9999	-0.53	11	11
PLCG1	-0.063	0.14	-9999	-0.32	75	75
PLD2	-0.075	0.16	-9999	-0.46	22	22
G12/G13	-0.007	0.1	-9999	-0.35	18	18
PI3K-beta	-0.041	0.097	-9999	-0.44	12	12
cell migration	-0.014	0.079	-9999	-0.26	12	12
SLC9A3R2	0.008	0.047	-9999	-0.51	3	3
PXN	-0.036	0.11	-9999	-0.34	21	21
HRAS/GTP	-0.02	0.13	-9999	-0.41	25	25
RAC1	0.012	0	-9999	-10000	0	0
MMP9	-0.076	0.2	-9999	-0.5	64	64
PRKCE	0.011	0.029	-9999	-0.54	1	1
PRKCD	-0.038	0.12	-9999	-0.35	20	20
Gi(beta/gamma)	-0.021	0.13	-9999	-0.41	25	25
mol:LPA	-0.012	0.049	-9999	-0.18	17	17
TRIP6/p130 Cas/FAK1/Paxillin	-0.054	0.15	-9999	-0.45	21	21
MAPKKK cascade	-0.019	0.13	-9999	-0.4	25	25
contractile ring contraction involved in cytokinesis	0.012	0.043	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.065	0.13	-9999	-0.3	79	79
GNA15	-0.067	0.14	-9999	-0.32	75	75
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
MAPT	-0.016	0.096	-9999	-0.34	12	12
GNA11	-0.064	0.14	-9999	-0.3	75	75
Rac1/GTP	0.001	0.15	-9999	-0.94	9	9
MMP2	-0.049	0.19	-9999	-0.51	51	51

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.011	0.029	-10000	0	-0.54	1	1
PTK2	0.012	0	-10000	0	-10000	0	0
CRKL	-0.045	0.14	-10000	0	-0.34	55	55
GRB2/SOS1/SHC	0.025	0	-10000	0	-10000	0	0
HRAS	0.011	0.024	-10000	0	-0.45	1	1
IRS1/Crk	-0.045	0.14	-10000	0	-0.34	55	55
IGF-1R heterotetramer/IGF1/PTP1B	-0.048	0.14	-10000	0	-0.35	55	55
AKT1	-0.038	0.14	-10000	0	-0.44	26	26
BAD	-0.03	0.14	-10000	0	-0.41	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.045	0.14	-10000	0	-0.34	55	55
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.045	0.14	-10000	0	-0.34	55	55
RAF1	-0.023	0.13	-10000	0	-0.4	22	22
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.035	0.14	-10000	0	-0.32	55	55
YWHAZ	0.012	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.056	0.15	-10000	0	-0.36	61	61
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
RPS6KB1	-0.038	0.14	-10000	0	-0.44	26	26
GNB2L1	0.012	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.021	0.11	-10000	0	-0.35	22	22
PXN	0.012	0	-10000	0	-10000	0	0
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
HRAS/GTP	-0.052	0.11	-10000	0	-0.44	16	16
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.022	0.12	-10000	0	-0.38	16	16
IGF-1R heterotetramer	-0.042	0.16	-10000	0	-0.58	28	28
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.044	0.14	-10000	0	-0.34	56	56
Crk/p130 Cas/Paxillin	-0.029	0.13	-10000	0	-0.47	16	16
IGF1R	-0.042	0.16	-10000	0	-0.58	28	28
IGF1	-0.075	0.19	-10000	0	-0.52	57	57
IRS2/Crk	-0.06	0.15	-10000	0	-0.44	31	31
PI3K	-0.051	0.16	-10000	0	-0.44	35	35
apoptosis	0.019	0.12	0.36	23	-10000	0	23
HRAS/GDP	0.008	0.017	-10000	0	-0.32	1	1
PRKCD	-0.037	0.16	-10000	0	-0.43	39	39
RAF1/14-3-3 E	-0.013	0.12	-10000	0	-0.35	19	19
BAD/14-3-3	-0.021	0.13	-10000	0	-0.39	23	23
PRKCZ	-0.039	0.14	-10000	0	-0.45	26	26
Crk/p130 Cas/Paxillin/FAK1	-0.054	0.11	-10000	0	-0.39	22	22
PTPN1	0.012	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.044	0.16	-10000	0	-0.4	55	55
BCAR1	0.011	0.029	-10000	0	-0.54	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.04	0.14	-10000	0	-0.32	60	60
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.012	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.045	0.14	-10000	0	-0.34	56	56
GRB10	0	0.08	-10000	0	-0.54	8	8
PTPN11	-0.045	0.14	-10000	0	-0.34	55	55
IRS1	-0.056	0.15	-10000	0	-0.35	61	61
IRS2	-0.07	0.16	-10000	0	-0.36	64	64
IGF-1R heterotetramer/IGF1	-0.075	0.18	-10000	0	-0.41	78	78
GRB2	0.012	0	-10000	0	-10000	0	0
PDPK1	-0.045	0.15	-10000	0	-0.47	26	26
YWHAE	0.012	0	-10000	0	-10000	0	0
PRKD1	-0.049	0.17	-10000	0	-0.45	42	42
SHC1	0.012	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.026	0.13	0.19	1	-0.33	43	44
ACTA1	-0.042	0.16	0.22	5	-0.4	47	52
NUMA1	-0.026	0.13	0.19	1	-0.32	46	47
SPTAN1	-0.037	0.16	0.22	4	-0.39	46	50
LIMK1	-0.037	0.16	0.22	4	-0.39	46	50
BIRC3	-0.047	0.16	-10000	0	-0.51	42	42
BIRC2	0.009	0.04	-10000	0	-0.54	2	2
BAX	0.012	0	-10000	0	-10000	0	0
CASP10	-0.06	0.17	-10000	0	-0.37	79	79
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0	-10000	0	-10000	0	0
PTK2	-0.026	0.13	0.19	1	-0.32	46	47
DIABLO	0.012	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.036	0.16	0.22	4	-0.39	46	50
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.012	0	-10000	0	-10000	0	0
GSN	-0.038	0.16	0.23	4	-0.4	46	50
MADD	0.012	0	-10000	0	-10000	0	0
TFAP2A	-0.1	0.24	-10000	0	-0.58	65	65
BID	-0.023	0.091	-10000	0	-0.22	55	55
MAP3K1	-0.008	0.061	-10000	0	-0.21	8	8
TRADD	0.009	0.04	-10000	0	-0.54	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.018	0.017	-10000	0	-0.31	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.037	0.16	0.22	4	-0.4	46	50
CASP9	0.011	0.024	-10000	0	-0.45	1	1
DNA repair	-0.005	0.053	-10000	0	-0.18	13	13
neuron apoptosis	0.012	0.027	-10000	0	-0.31	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.029	0.15	0.21	1	-0.39	41	42
APAF1	0.012	0	-10000	0	-10000	0	0
CASP6	-0.01	0.087	-10000	0	-0.39	5	5
TRAF2	0.012	0	-10000	0	-10000	0	0
ICAD/CAD	-0.03	0.15	-10000	0	-0.39	41	41
CASP7	0.023	0.09	0.28	33	-0.47	1	34
KRT18	0.002	0.06	-10000	0	-0.72	2	2
apoptosis	-0.032	0.14	0.24	3	-0.35	41	44
DFFA	-0.037	0.16	0.22	4	-0.39	46	50
DFFB	-0.037	0.16	0.22	4	-0.4	43	47
PARP1	0.005	0.053	0.18	13	-10000	0	13
actin filament polymerization	0.029	0.15	0.37	41	-0.22	4	45
TNF	-0.069	0.19	-10000	0	-0.49	60	60
CYCS	-0.017	0.071	-10000	0	-0.21	24	24
SATB1	-0.027	0.11	-10000	0	-0.37	13	13
SLK	-0.038	0.16	0.22	4	-0.39	47	51
p15 BID/BAX	-0.014	0.082	-10000	0	-0.3	9	9
CASP2	-0.003	0.092	-10000	0	-0.38	9	9
JNK cascade	0.007	0.06	0.21	8	-10000	0	8
CASP3	-0.045	0.17	0.23	5	-0.42	47	52
LMNB2	0.002	0.071	-10000	0	-0.35	3	3
RIPK1	0.012	0	-10000	0	-10000	0	0
CASP4	0.005	0.064	-10000	0	-0.54	5	5
Mammalian IAPs/DIABLO	-0.003	0.099	-10000	0	-0.3	28	28
negative regulation of DNA binding	-0.1	0.23	-10000	0	-0.58	65	65
stress fiber formation	-0.037	0.16	0.22	4	-0.38	47	51
GZMB	-0.072	0.19	-10000	0	-0.44	73	73
CASP1	-0.002	0.077	-10000	0	-0.37	12	12
LMNB1	0.001	0.072	-10000	0	-0.32	4	4
APP	0.012	0.027	-10000	0	-0.32	1	1
TNFRSF1A	0.011	0.029	-10000	0	-0.54	1	1
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0.021	-10000	0	-0.39	1	1
VIM	-0.035	0.14	0.21	10	-0.34	42	52
LMNA	0.002	0.071	-10000	0	-0.35	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.097	-10000	0	-0.41	9	9
LRDD	0.011	0.029	-10000	0	-0.54	1	1
SREBF1	-0.038	0.16	0.22	4	-0.39	47	51
APAF-1/Caspase 9	0.004	0.047	0.36	2	-10000	0	2
nuclear fragmentation during apoptosis	-0.025	0.13	0.19	1	-0.32	46	47
CFL2	-0.03	0.15	0.22	3	-0.38	41	44
GAS2	-0.07	0.18	0.22	3	-0.38	70	73
positive regulation of apoptosis	0.004	0.072	-10000	0	-0.35	3	3
PRF1	-0.03	0.14	-10000	0	-0.49	31	31

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.043	0.14	0.36	58	-10000	0	58
KIRREL	-0.047	0.16	-10000	0	-0.51	41	41
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.043	0.14	-10000	0	-0.36	58	58
PLCG1	0.012	0	-10000	0	-10000	0	0
ARRB2	0.012	0	-10000	0	-10000	0	0
WASL	0.012	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.032	0.12	-10000	0	-0.32	40	40
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.008	0.084	-10000	0	-0.26	12	12
FYN	-0.024	0.097	-10000	0	-0.29	30	30
mol:Ca2+	-0.023	0.1	-10000	0	-0.3	30	30
mol:DAG	-0.022	0.1	-10000	0	-0.3	30	30
NPHS2	-0.008	0.045	-10000	0	-0.46	3	3
mol:IP3	-0.022	0.1	-10000	0	-0.3	30	30
regulation of endocytosis	-0.015	0.092	-10000	0	-0.27	27	27
Nephrin/NEPH1/podocin/Cholesterol	-0.03	0.1	-10000	0	-0.26	60	60
establishment of cell polarity	-0.043	0.14	-10000	0	-0.36	58	58
Nephrin/NEPH1/podocin/NCK1-2	-0.013	0.097	-10000	0	-0.35	5	5
Nephrin/NEPH1/beta Arrestin2	-0.014	0.094	-10000	0	-0.27	27	27
NPHS1	-0.019	0.1	-10000	0	-0.45	19	19
Nephrin/NEPH1/podocin	-0.024	0.098	-10000	0	-0.29	30	30
TJP1	0.012	0	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
NCK2	0.011	0.029	-10000	0	-0.54	1	1
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.022	0.1	-10000	0	-0.3	30	30
CD2AP	-0.004	0.093	-10000	0	-0.54	11	11
Nephrin/NEPH1/podocin/GRB2	-0.022	0.1	-10000	0	-0.3	30	30
GRB2	0.012	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.046	0.12	-10000	0	-0.28	63	63
cytoskeleton organization	-0.009	0.096	-10000	0	-0.3	12	12
Nephrin/NEPH1	-0.028	0.097	-10000	0	-0.25	58	58
Nephrin/NEPH1/ZO-1	-0.025	0.11	-10000	0	-0.28	58	58

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.042	0.16	-9999	-0.52	37	37
PDGF/PDGFRA/CRKL	-0.02	0.11	-9999	-0.36	37	37
positive regulation of JUN kinase activity	0.002	0.087	-9999	-0.27	30	30
CRKL	0.012	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.029	0.12	-9999	-0.36	39	39
AP1	-0.056	0.15	-9999	-0.52	24	24
mol:IP3	-0.02	0.12	-9999	-0.37	37	37
PLCG1	-0.02	0.12	-9999	-0.37	37	37
PDGF/PDGFRA/alphaV Integrin	-0.024	0.13	-9999	-0.38	40	40
RAPGEF1	0.012	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
mol:Ca2+	-0.02	0.12	-9999	-0.37	37	37
CAV3	0	0.034	-9999	-0.45	2	2
CAV1	0.006	0.056	-9999	-0.47	5	5
SHC/Grb2/SOS1	0.003	0.088	-9999	-0.27	30	30
PDGF/PDGFRA/Shf	-0.026	0.13	-9999	-0.38	42	42
FOS	-0.024	0.16	-9999	-0.52	24	24
JUN	-0.007	0.03	-9999	-0.38	2	2
oligodendrocyte development	-0.024	0.12	-9999	-0.38	40	40
GRB2	0.012	0	-9999	-10000	0	0
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
mol:DAG	-0.02	0.12	-9999	-0.37	37	37
PDGF/PDGFRA	-0.041	0.16	-9999	-0.52	37	37
actin cytoskeleton reorganization	-0.021	0.12	-9999	-0.36	38	38
SRF	0.019	0.006	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
PI3K	-0.027	0.13	-9999	-0.34	49	49
PDGF/PDGFRA/Crk/C3G	-0.007	0.097	-9999	-0.3	37	37
JAK1	-0.024	0.12	-9999	-0.36	42	42
ELK1/SRF	0.003	0.089	-9999	-0.28	30	30
SHB	0.011	0.029	-9999	-0.54	1	1
SHF	0.002	0.072	-9999	-0.51	7	7
CSNK2A1	0.012	0.011	-9999	-10000	0	0
GO:0007205	-0.021	0.12	-9999	-0.39	37	37
SOS1	0.012	0	-9999	-10000	0	0
Ras protein signal transduction	0.002	0.087	-9999	-0.27	30	30
PDGF/PDGFRA/SHB	-0.021	0.12	-9999	-0.36	38	38
PDGF/PDGFRA/Caveolin-1	-0.024	0.12	-9999	-0.36	41	41
ITGAV	0.005	0.062	-9999	-0.52	5	5
ELK1	-0.012	0.11	-9999	-0.35	31	31
PIK3CA	0.01	0.034	-9999	-0.45	2	2
PDGF/PDGFRA/Crk	-0.02	0.11	-9999	-0.36	37	37
JAK-STAT cascade	-0.024	0.12	-9999	-0.36	42	42
cell proliferation	-0.026	0.13	-9999	-0.38	42	42

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.04	-9999	-0.33	5	5
alphaV beta3 Integrin	-0.052	0.14	-9999	-0.3	89	89
PTK2	-0.031	0.14	-9999	-0.47	14	14
IGF1R	-0.029	0.15	-9999	-0.54	28	28
PI4KB	0.011	0.024	-9999	-0.45	1	1
MFGE8	0.003	0.07	-9999	-0.5	7	7
SRC	0.009	0.04	-9999	-0.54	2	2
CDKN1B	-0.041	0.14	-9999	-0.5	22	22
VEGFA	0.009	0.042	-9999	-0.45	3	3
ILK	-0.018	0.074	-9999	-0.32	6	6
ROCK1	0.012	0	-9999	-10000	0	0
AKT1	-0.009	0.07	-9999	-0.32	4	4
PTK2B	-0.017	0.11	-9999	-0.57	3	3
alphaV/beta3 Integrin/JAM-A	-0.044	0.14	-9999	-0.31	47	47
CBL	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.035	0.13	-9999	-0.3	64	64
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.049	0.16	-9999	-0.36	61	61
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.001	0.078	-9999	-0.33	5	5
alphaV/beta3 Integrin/Syndecan-1	-0.039	0.13	-9999	-0.29	75	75
PI4KA	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.18	-9999	-0.52	46	46
PI4 Kinase	0.017	0.017	-9999	-0.31	1	1
PIK3CA	0.01	0.034	-9999	-0.45	2	2
alphaV/beta3 Integrin/Osteopontin	-0.054	0.16	-9999	-0.33	82	82
RPS6KB1	-0.093	0.19	-9999	-0.49	46	46
TLN1	0.012	0	-9999	-10000	0	0
MAPK3	-0.074	0.18	-9999	-0.51	44	44
GPR124	-0.001	0.083	-9999	-0.5	10	10
MAPK1	-0.074	0.18	-9999	-0.5	45	45
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
alphaV/beta3 Integrin/Tumstatin	-0.07	0.16	-9999	-0.33	99	99
cell adhesion	-0.027	0.12	-9999	-0.36	29	29
ANGPTL3	0.002	0.041	-9999	-0.45	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.019	0.042	-9999	-0.28	7	7
IGF-1R heterotetramer	-0.029	0.14	-9999	-0.54	28	28
Rac1/GDP	0.009	0	-9999	-10000	0	0
TGFBR2	0.009	0.04	-9999	-0.54	2	2
ITGB3	-0.068	0.18	-9999	-0.48	60	60
IGF1	-0.067	0.19	-9999	-0.5	57	57
RAC1	0.012	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.036	0.14	-9999	-0.31	68	68
apoptosis	0.005	0.061	-9999	-0.52	5	5
CD47	0.007	0.05	-9999	-0.47	4	4
alphaV/beta3 Integrin/CD47	-0.032	0.12	-9999	-0.29	67	67
VCL	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.067	0.16	-9999	-0.32	98	98
CSF1	0.002	0.073	-9999	-0.53	7	7
PIK3C2A	-0.018	0.074	-9999	-0.32	6	6
PI4 Kinase/Pyk2	-0.057	0.1	-9999	-0.43	9	9
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.12	-9999	-0.31	26	26
FAK1/Vinculin	-0.018	0.12	-9999	-0.38	13	13
alphaV beta3/Integrin/ppsTEM5	-0.036	0.14	-9999	-0.31	68	68
RHOA	0.012	0	-9999	-10000	0	0
VTN	-0.009	0.095	-9999	-0.46	16	16
BCAR1	0.011	0.029	-9999	-0.54	1	1
FGF2	-0.027	0.14	-9999	-0.5	28	28
F11R	-0.012	0.11	-9999	-0.37	30	30
alphaV/beta3 Integrin/Lactadherin	-0.034	0.13	-9999	-0.31	66	66
alphaV/beta3 Integrin/TGFBR2	-0.03	0.12	-9999	-0.29	64	64
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.021	0.057	-9999	-0.28	11	11
HSP90AA1	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.025	0.11	-9999	-0.26	63	63
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.02	0.12	-9999	-0.47	25	25
alphaV/beta3 Integrin/Pyk2	-0.015	0.11	-9999	-0.57	3	3
SDC1	-0.005	0.095	-9999	-0.52	12	12
VAV3	0.001	0.095	-9999	-0.54	2	2
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	-0.011	0.11	-9999	-0.53	16	16
FAK1/Paxillin	-0.018	0.12	-9999	-0.38	13	13
cell migration	-0.01	0.11	-9999	-0.34	13	13
ITGAV	0.005	0.062	-9999	-0.52	5	5
PI3K	-0.075	0.13	-9999	-0.46	19	19
SPP1	-0.032	0.14	-9999	-0.5	32	32
KDR	0.01	0.037	-9999	-0.5	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.005	0.062	-9999	-0.52	5	5
COL4A3	-0.057	0.17	-9999	-0.49	50	50
angiogenesis	-0.07	0.19	-9999	-0.51	45	45
Rac1/GTP	0.008	0.088	-9999	-0.49	2	2
EDIL3	-0.051	0.17	-9999	-0.52	44	44
cell proliferation	-0.03	0.12	-9999	-0.29	64	64

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.019	0.11	-10000	0	-0.28	52	52
ER alpha/Gai/GDP/Gbeta gamma	-0.034	0.15	-10000	0	-0.38	51	51
AKT1	-0.082	0.28	-10000	0	-0.78	48	48
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.086	0.28	-10000	0	-0.79	48	48
mol:Ca2+	-0.018	0.14	-10000	0	-0.44	26	26
IGF1R	-0.029	0.15	-10000	0	-0.54	28	28
E2/ER alpha (dimer)/Striatin	-0.032	0.12	-10000	0	-0.33	52	52
SHC1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.077	0.26	0.74	48	-10000	0	48
RhoA/GTP	-0.034	0.087	-10000	0	-0.48	3	3
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.067	0.14	-10000	0	-0.41	51	51
regulation of stress fiber formation	-0.009	0.084	0.37	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.03	0.12	-10000	0	-0.32	51	51
KRAS	0.012	0	-10000	0	-10000	0	0
G13/GTP	-0.025	0.1	-10000	0	-0.3	48	48
pseudopodium formation	0.009	0.084	-10000	0	-0.37	4	4
E2/ER alpha (dimer)/PELP1	-0.028	0.12	-10000	0	-0.33	48	48
GRB2	0.012	0	-10000	0	-10000	0	0
GNG2	-0.002	0.084	-10000	0	-0.48	11	11
GNAO1	-0.014	0.11	-10000	0	-0.47	20	20
HRAS	0.011	0.024	-10000	0	-0.45	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.041	0.18	-10000	0	-0.47	51	51
E2/ER beta (dimer)	0.006	0.032	-10000	0	-0.34	3	3
mol:GDP	-0.053	0.13	-10000	0	-0.39	49	49
mol:NADP	-0.041	0.18	-10000	0	-0.47	51	51
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
mol:IP3	-0.019	0.14	-10000	0	-0.46	26	26
IGF-1R heterotetramer	-0.029	0.14	-10000	0	-0.54	28	28
PLCB1	-0.019	0.13	-10000	0	-0.46	23	23
PLCB2	-0.014	0.13	-10000	0	-0.48	18	18
IGF1	-0.067	0.19	-10000	0	-0.5	57	57
mol:L-citrulline	-0.041	0.18	-10000	0	-0.47	51	51
RHOA	0.012	0	-10000	0	-10000	0	0
Gai/GDP	-0.003	0.1	-10000	0	-0.57	8	8
JNK cascade	0.006	0.032	-10000	0	-0.34	3	3
BCAR1	0.011	0.029	-10000	0	-0.54	1	1
ESR2	0.008	0.044	-10000	0	-0.48	3	3
GNAQ	0.011	0.029	-10000	0	-0.54	1	1
ESR1	-0.059	0.18	-10000	0	-0.54	48	48
Gq family/GDP/Gbeta gamma	-0.001	0.12	-10000	0	-0.5	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.005	0.096	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.067	0.14	-10000	0	-0.41	50	50
GNAZ	-0.005	0.094	-10000	0	-0.52	12	12
E2/ER alpha (dimer)	-0.043	0.14	-10000	0	-0.39	48	48
STRN	0.006	0.057	-10000	0	-0.54	4	4
GNAL	-0.01	0.1	-10000	0	-0.48	17	17
PELP1	0.012	0	-10000	0	-10000	0	0
MAPK11	0.011	0.038	-10000	0	-0.28	6	6
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.095	-10000	0	-0.52	12	12
HBEGF	-0.054	0.16	-10000	0	-0.45	30	30
cAMP biosynthetic process	-0.046	0.1	-10000	0	-0.27	63	63
SRC	-0.028	0.14	-10000	0	-0.35	50	50
PI3K	-0.006	0.093	-10000	0	-0.37	23	23
GNB1	0.012	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.052	0.12	-10000	0	-0.35	49	49
SOS1	0.012	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.092	0.16	-10000	0	-0.41	58	58
Gs family/GTP	-0.046	0.1	-10000	0	-0.27	63	63
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.019	0.039	-10000	0	-0.28	6	6
vasodilation	-0.038	0.17	-10000	0	-0.45	51	51
mol:DAG	-0.019	0.14	-10000	0	-0.46	26	26
Gs family/GDP/Gbeta gamma	-0.057	0.12	-10000	0	-0.35	50	50
MSN	0.008	0.089	-10000	0	-0.4	4	4
Gq family/GTP	-0.015	0.12	-10000	0	-0.55	14	14
mol:PI-3-4-5-P3	-0.081	0.27	-10000	0	-0.76	48	48
NRAS	0.005	0.064	-10000	0	-0.54	5	5
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.038	0.17	0.45	51	-10000	0	51
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
RhoA/GDP	-0.05	0.12	-10000	0	-0.36	49	49
NOS3	-0.044	0.19	-10000	0	-0.49	51	51
GNA11	-0.001	0.082	-10000	0	-0.52	9	9
MAPKKK cascade	-0.041	0.2	-10000	0	-0.55	49	49
E2/ER alpha (dimer)/PELP1/Src	-0.07	0.15	-10000	0	-0.43	50	50
ruffle organization	0.009	0.084	-10000	0	-0.37	4	4
ROCK2	0.003	0.093	-10000	0	-0.44	3	3
GNA14	-0.003	0.089	-10000	0	-0.54	10	10
GNA15	-0.005	0.093	-10000	0	-0.51	12	12
GNA13	0.012	0	-10000	0	-10000	0	0
MMP9	-0.062	0.17	-10000	0	-0.48	28	28
MMP2	-0.045	0.16	-10000	0	-0.47	26	26

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.012	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.05	-9999	-0.32	9	9
Metarhodopsin II/Arrestin	0.002	0.04	-9999	-0.26	8	8
PDE6G/GNAT1/GTP	-0.04	0.12	-9999	-0.3	62	62
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.071	-9999	-0.45	9	9
GRK1	-0.008	0.07	-9999	-0.45	9	9
CNG Channel	-0.14	0.18	-9999	-0.5	54	54
mol:Na +	-0.082	0.14	-9999	-0.46	27	27
mol:ADP	-0.008	0.07	-9999	-0.45	9	9
RGS9-1/Gbeta5/R9AP	-0.039	0.14	-9999	-0.33	66	66
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.082	0.15	-9999	-0.48	27	27
CNGB1	-0.058	0.17	-9999	-0.49	51	51
RDH5	-0.015	0.11	-9999	-0.47	21	21
SAG	0.002	0.041	-9999	-0.45	3	3
mol:Ca2+	-0.054	0.15	-9999	-0.45	27	27
Na + (4 Units)	-0.077	0.13	-9999	-0.43	27	27
RGS9	-0.054	0.17	-9999	-0.49	49	49
GNB1/GNGT1	-0.015	0.11	-9999	-0.38	30	30
GNAT1/GDP	-0.035	0.13	-9999	-0.37	34	34
GUCY2D	-0.008	0.088	-9999	-0.45	14	14
GNGT1	-0.033	0.15	-9999	-0.54	30	30
GUCY2F	0.003	0.034	-9999	-0.45	2	2
GNB5	0.006	0.057	-9999	-0.54	4	4
mol:GMP (4 units)	-0.078	0.16	-9999	-0.35	71	71
mol:11-cis-retinal	-0.015	0.11	-9999	-0.47	21	21
mol:cGMP	-0.015	0.1	-9999	-0.39	9	9
GNB1	0.012	0	-9999	-10000	0	0
Rhodopsin	-0.011	0.09	-9999	-0.34	25	25
SLC24A1	0.012	0	-9999	-10000	0	0
CNGA1	-0.044	0.16	-9999	-0.51	40	40
Metarhodopsin II	-0.004	0.047	-9999	-0.24	14	14
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.11	-9999	-0.36	16	16
RGS9BP	-0.022	0.12	-9999	-0.45	26	26
Metarhodopsin II/Transducin	-0.011	0.078	-9999	-0.26	31	31
GCAP Family/Ca ++	-0.014	0.087	-9999	-0.27	36	36
PDE6A/B	-0.063	0.15	-9999	-0.34	83	83
mol:Pi	-0.039	0.14	-9999	-0.33	66	66
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.011	0.093	-9999	-0.28	39	39
PDE6B	-0.098	0.21	-9999	-0.48	82	82
PDE6A	0.01	0.034	-9999	-0.45	2	2
PDE6G	-0.063	0.18	-9999	-0.48	56	56
RHO	-0.001	0.053	-9999	-0.45	5	5
PDE6	-0.11	0.2	-9999	-0.5	52	52
GUCA1A	-0.009	0.088	-9999	-0.45	14	14
GC2/GCAP Family	-0.011	0.089	-9999	-0.32	13	13
GUCA1C	-0.005	0.052	-9999	-0.45	5	5
GUCA1B	-0.014	0.12	-9999	-0.51	19	19

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.038	0.15	-10000	0	-0.44	29	29
CRKL	-0.038	0.15	-10000	0	-0.45	30	30
HRAS	-0.033	0.15	-10000	0	-0.44	25	25
mol:PIP3	-0.047	0.15	0.23	1	-0.42	36	37
SPRED1	0.012	0	-10000	0	-10000	0	0
SPRED2	0.012	0	-10000	0	-10000	0	0
GAB1	-0.046	0.16	-10000	0	-0.46	34	34
FOXO3	-0.033	0.14	-10000	0	-0.42	29	29
AKT1	-0.042	0.15	-10000	0	-0.45	31	31
BAD	-0.033	0.14	-10000	0	-0.42	29	29
megakaryocyte differentiation	-0.056	0.17	-10000	0	-0.45	42	42
GSK3B	-0.033	0.14	-10000	0	-0.43	28	28
RAF1	-0.019	0.13	-10000	0	-0.35	23	23
SHC1	0.012	0	-10000	0	-10000	0	0
STAT3	-0.045	0.16	-10000	0	-0.46	34	34
STAT1	-0.1	0.33	-10000	0	-0.98	35	35
HRAS/SPRED1	-0.02	0.13	-10000	0	-0.36	21	21
cell proliferation	-0.045	0.16	-10000	0	-0.45	34	34
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
TEC	0.002	0.073	-10000	0	-0.53	7	7
RPS6KB1	-0.046	0.16	-10000	0	-0.46	35	35
HRAS/SPRED2	-0.02	0.13	-10000	0	-0.36	21	21
LYN/TEC/p62DOK	-0.037	0.16	-10000	0	-0.47	32	32
MAPK3	-0.003	0.096	-10000	0	-0.26	15	15
STAP1	-0.059	0.16	-10000	0	-0.45	38	38
GRAP2	-0.028	0.14	-10000	0	-0.5	29	29
JAK2	-0.091	0.29	-10000	0	-0.84	36	36
STAT1 (dimer)	-0.1	0.32	-10000	0	-0.95	35	35
mol:Gleevec	0.001	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.045	0.16	-10000	0	-0.44	38	38
actin filament polymerization	-0.048	0.16	-10000	0	-0.45	34	34
LYN	0.008	0.049	-10000	0	-0.54	3	3
STAP1/STAT5A (dimer)	-0.07	0.21	-10000	0	-0.62	34	34
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
CBL/CRKL/GRB2	-0.022	0.14	-10000	0	-0.42	25	25
PI3K	-0.048	0.17	-10000	0	-0.49	35	35
PTEN	0.002	0.075	-10000	0	-0.54	7	7
SCF/KIT/EPO/EPOR	-0.12	0.38	-10000	0	-1.3	30	30
MAPK8	-0.047	0.16	-10000	0	-0.46	34	34
STAT3 (dimer)	-0.044	0.15	-10000	0	-0.45	34	34
positive regulation of transcription	0.001	0.082	-10000	0	-0.23	9	9
mol:GDP	-0.04	0.16	-10000	0	-0.42	37	37
PIK3C2B	-0.045	0.16	-10000	0	-0.46	34	34
CBL/CRKL	-0.029	0.14	-10000	0	-0.42	28	28
FER	-0.047	0.16	-10000	0	-0.46	35	35
SH2B3	-0.045	0.16	-10000	0	-0.46	34	34
PDPK1	-0.039	0.14	-10000	0	-0.4	31	31
SNAI2	-0.055	0.17	-10000	0	-0.47	40	40
positive regulation of cell proliferation	-0.075	0.25	-10000	0	-0.73	36	36
KITLG	-0.037	0.16	-10000	0	-0.51	35	35
cell motility	-0.075	0.25	-10000	0	-0.73	36	36
PTPN6	0.009	0.05	-10000	0	-0.53	3	3
EPOR	-0.033	0.2	-10000	0	-1.2	7	7
STAT5A (dimer)	-0.062	0.21	-10000	0	-0.61	36	36
SOCS1	0.004	0.066	-10000	0	-0.51	6	6
cell migration	0.06	0.16	0.44	40	-10000	0	40
SOS1	0.012	0	-10000	0	-10000	0	0
EPO	-0.017	0.1	-10000	0	-0.45	20	20
VAV1	-0.009	0.1	-10000	0	-0.52	15	15
GRB10	-0.051	0.16	-10000	0	-0.46	36	36
PTPN11	0.013	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.054	0.16	-10000	0	-0.47	36	36
GO:0007205	0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.007	0.1	-10000	0	-0.29	16	16
CBL	0.012	0	-10000	0	-10000	0	0
KIT	-0.085	0.33	-10000	0	-1.3	23	23
MAP2K2	-0.007	0.1	-10000	0	-0.29	16	16
SHC/Grb2/SOS1	-0.031	0.15	-10000	0	-0.44	30	30
STAT5A	-0.064	0.22	-10000	0	-0.63	36	36
GRB2	0.012	0	-10000	0	-10000	0	0
response to radiation	-0.053	0.17	-10000	0	-0.46	40	40
SHC/GRAP2	-0.011	0.1	-10000	0	-0.36	29	29
PTPRO	-0.058	0.17	-10000	0	-0.46	42	42
SH2B2	-0.049	0.16	-10000	0	-0.46	34	34
DOK1	0.012	0	-10000	0	-10000	0	0
MATK	-0.062	0.17	-10000	0	-0.45	40	40
CREBBP	0.019	0.034	-10000	0	-10000	0	0
BCL2	-0.052	0.28	-10000	0	-1.3	15	15

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.013	0.099	-9999	-0.29	42	42
EPHB2	-0.051	0.17	-9999	-0.51	45	45
Syndecan-2/TACI	-0.021	0.11	-9999	-0.29	48	48
LAMA1	-0.14	0.24	-9999	-0.52	102	102
Syndecan-2/alpha2 ITGB1	-0.022	0.13	-9999	-0.3	58	58
HRAS	0.011	0.024	-9999	-0.45	1	1
Syndecan-2/CASK	-0.002	0.069	-9999	-0.32	17	17
ITGA5	0.01	0.037	-9999	-0.5	2	2
BAX	0.018	0.066	-9999	-10000	0	0
EPB41	0.012	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.006	0.063	-9999	-0.28	17	17
LAMA3	-0.027	0.14	-9999	-0.53	27	27
EZR	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.049	-9999	-0.54	3	3
Syndecan-2/MMP2	-0.026	0.12	-9999	-0.3	54	54
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.013	0.11	-9999	-0.37	30	30
dendrite morphogenesis	-0.032	0.12	-9999	-0.31	61	61
Syndecan-2/GM-CSF	-0.003	0.084	-9999	-0.32	23	23
determination of left/right symmetry	-0.001	0.082	-9999	-0.38	17	17
Syndecan-2/PKC delta	0.005	0.074	-9999	-0.31	19	19
GNB2L1	0.012	0	-9999	-10000	0	0
MAPK3	0.004	0.078	-9999	-0.32	15	15
MAPK1	0.004	0.078	-9999	-0.32	15	15
Syndecan-2/RACK1	0.013	0.061	-9999	-0.26	16	16
NF1	0.008	0.049	-9999	-0.54	3	3
FGFR/FGF/Syndecan-2	-0.001	0.082	-9999	-0.38	17	17
ITGA2	-0.031	0.15	-9999	-0.52	30	30
MAPK8	0.011	0.074	-9999	-0.31	19	19
Syndecan-2/alpha2/beta1 Integrin	-0.08	0.16	-9999	-0.3	113	113
Syndecan-2/Kininogen	-0.011	0.09	-9999	-0.28	36	36
ITGB1	0.012	0	-9999	-10000	0	0
SRC	0.016	0.064	-9999	-0.26	16	16
Syndecan-2/CASK/Protein 4.1	0.006	0.063	-9999	-0.28	17	17
extracellular matrix organization	0.005	0.072	-9999	-0.3	19	19
actin cytoskeleton reorganization	-0.013	0.099	-9999	-0.29	42	42
Syndecan-2/Caveolin-2/Ras	0.011	0.073	-9999	-0.29	20	20
Syndecan-2/Laminin alpha3	-0.018	0.11	-9999	-0.33	42	42
Syndecan-2/RasGAP	0.019	0.059	-9999	-0.25	15	15
alpha5/beta1 Integrin	0.016	0.027	-9999	-0.35	2	2
PRKCD	0.009	0.04	-9999	-0.54	2	2
Syndecan-2 dimer	-0.033	0.12	-9999	-0.31	61	61
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.023	0.063	-9999	-0.5	1	1
RHOA	0.012	0	-9999	-10000	0	0
SDCBP	0.012	0	-9999	-10000	0	0
TNFRSF13B	-0.034	0.14	-9999	-0.46	34	34
RASA1	0.012	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.013	0.11	-9999	-0.37	30	30
Syndecan-2/Synbindin	0.007	0.07	-9999	-0.31	17	17
TGFB1	0.01	0.034	-9999	-0.45	2	2
CASP3	0.012	0.067	-9999	-0.28	19	19
FN1	-0.02	0.12	-9999	-0.47	25	25
Syndecan-2/IL8	-0.042	0.14	-9999	-0.31	70	70
SDC2	-0.001	0.082	-9999	-0.38	17	17
KNG1	-0.017	0.1	-9999	-0.45	19	19
Syndecan-2/Neurofibromin	0.004	0.078	-9999	-0.33	19	19
TRAPPC4	0.012	0	-9999	-10000	0	0
CSF2	-0.003	0.067	-9999	-0.45	8	8
Syndecan-2/TGFB1	0.005	0.073	-9999	-0.31	19	19
Syndecan-2/Syntenin/PI-4-5-P2	0.006	0.063	-9999	-0.28	17	17
Syndecan-2/Ezrin	0.014	0.064	-9999	-0.28	15	15
PRKACA	0.011	0.071	-9999	-0.3	18	18
angiogenesis	-0.041	0.14	-9999	-0.31	70	70
MMP2	-0.04	0.16	-9999	-0.5	38	38
IL8	-0.067	0.18	-9999	-0.5	58	58
calcineurin-NFAT signaling pathway	-0.021	0.11	-9999	-0.29	48	48

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0.078	-9999	-0.49	9	9
alphaV beta3 Integrin	-0.044	0.14	-9999	-0.35	63	63
PTK2	-0.046	0.16	-9999	-0.46	37	37
positive regulation of JNK cascade	-0.035	0.093	-9999	-0.3	38	38
CDC42/GDP	-0.012	0.14	-9999	-0.41	39	39
Rac1/GDP	-0.011	0.14	-9999	-0.41	39	39
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.011	0.029	-9999	-0.54	1	1
CDC42/GTP	-0.043	0.12	-9999	-0.38	38	38
nectin-3/I-afadin	-0.03	0.13	-9999	-0.37	46	46
RAPGEF1	-0.022	0.15	-9999	-0.46	38	38
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.034	0.17	-9999	-0.53	38	38
PDGFB-D/PDGFRB	0	0.078	-9999	-0.49	9	9
TLN1	-0.032	0.13	-9999	-0.35	39	39
Rap1/GTP	-0.037	0.099	-9999	-0.32	38	38
IQGAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.023	0.016	-9999	-0.29	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.03	0.13	-9999	-0.37	46	46
PVR	0.012	0	-9999	-10000	0	0
Necl-5(dimer)	0.012	0	-9999	-10000	0	0
mol:GDP	-0.024	0.17	-9999	-0.51	39	39
MLLT4	0.011	0.029	-9999	-0.54	1	1
PIK3CA	0.01	0.034	-9999	-0.45	2	2
PI3K	-0.023	0.13	-9999	-0.51	9	9
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.014	0.04	-9999	-0.37	4	4
positive regulation of lamellipodium assembly	-0.039	0.1	-9999	-0.33	39	39
PVRL1	0.008	0.047	-9999	-0.51	3	3
PVRL3	-0.053	0.18	-9999	-0.52	45	45
PVRL2	0.011	0.029	-9999	-0.54	1	1
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
CDH1	0.002	0.075	-9999	-0.54	7	7
CLDN1	-0.062	0.18	-9999	-0.51	53	53
JAM-A/CLDN1	-0.05	0.15	-9999	-0.32	69	69
SRC	-0.045	0.19	-9999	-0.59	38	38
ITGB3	-0.068	0.18	-9999	-0.48	60	60
nectin-1(dimer)/I-afadin/I-afadin	0.014	0.04	-9999	-0.37	4	4
FARP2	-0.026	0.16	-9999	-0.5	38	38
RAC1	0.012	0	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.016	0.11	-9999	-0.31	46	46
nectin-1/I-afadin	0.014	0.04	-9999	-0.37	4	4
nectin-2/I-afadin	0.016	0.03	-9999	-0.38	2	2
RAC1/GTP/IQGAP1/filamentous actin	0.017	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.019	0.12	-9999	-0.31	48	48
CDC42/GTP/IQGAP1/filamentous actin	0.017	0	-9999	-10000	0	0
F11R	0.008	0.049	-9999	-0.54	3	3
positive regulation of filopodium formation	-0.035	0.093	-9999	-0.3	38	38
alphaV/beta3 Integrin/Talin	-0.058	0.16	-9999	-0.38	50	50
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0.03	-9999	-0.38	2	2
nectin-2(dimer)/I-afadin/I-afadin	0.016	0.03	-9999	-0.38	2	2
PIP5K1C	-0.041	0.13	-9999	-0.38	39	39
VAV2	-0.032	0.18	-9999	-0.53	40	40
RAP1/GDP	-0.042	0.12	-9999	-0.38	39	39
ITGAV	0.005	0.062	-9999	-0.52	5	5
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.017	0.11	-9999	-0.31	47	47
nectin-3(dimer)/I-afadin/I-afadin	-0.03	0.13	-9999	-0.37	46	46
Rac1/GTP	-0.047	0.12	-9999	-0.4	39	39
PTPRM	-0.052	0.15	-9999	-0.32	74	74
E-cadherin/beta catenin/alpha catenin	0.027	0.055	-9999	-0.51	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.012	0	-9999	-10000	0	0

×

Canonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.025	-10000	0	-10000	0	0
AES	0.015	0.036	-10000	0	-0.54	1	1
FBXW11	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.016	0.032	-10000	0	-0.34	3	3
SMAD4	0.011	0.029	-10000	0	-0.54	1	1
DKK2	-0.087	0.2	-10000	0	-0.5	72	72
TLE1	0.014	0.046	-10000	0	-0.54	2	2
MACF1	0.013	0.001	-10000	0	-10000	0	0
CTNNB1	0.068	0.087	0.28	12	-10000	0	12
WIF1	-0.25	0.25	-10000	0	-0.49	193	193
beta catenin/RanBP3	0.052	0.14	0.4	41	-10000	0	41
KREMEN2	-0.053	0.17	-10000	0	-0.48	49	49
DKK1	-0.18	0.24	-10000	0	-0.48	142	142
beta catenin/beta TrCP1	0.071	0.082	0.27	11	-10000	0	11
FZD1	0.009	0.044	-10000	0	-0.48	3	3
AXIN2	-0.055	0.26	-10000	0	-1.3	13	13
AXIN1	0.013	0.001	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.033	0.036	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.005	0.14	-10000	0	-0.46	11	11
Axin1/APC/GSK3	0.052	0.057	0.25	5	-10000	0	5
Axin1/APC/GSK3/beta catenin/Macf1	0.056	0.052	0.3	1	-0.38	1	2
HNF1A	-0.093	0.22	-10000	0	-0.53	74	74
CTBP1	0.017	0.021	-10000	0	-10000	0	0
MYC	-0.024	0.22	-10000	0	-1.4	9	9
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.075	0.16	-10000	0	-0.32	108	108
NKD1	-0.093	0.2	-10000	0	-0.46	82	82
TCF4	0.009	0.065	-10000	0	-0.51	5	5
TCF3	0.015	0.033	-10000	0	-0.47	1	1
WNT1/LRP6/FZD1/Axin1	0.023	0.053	-10000	0	-0.51	1	1
Ran/GTP	0.01	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.008	0.16	0.43	17	-0.41	10	27
LEF1	-0.057	0.18	-10000	0	-0.52	50	50
DVL1	0.062	0.044	0.21	2	-10000	0	2
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.014	0.16	-10000	0	-0.48	17	17
DKK1/LRP6/Kremen 2	-0.13	0.17	-10000	0	-0.36	74	74
LRP6	0.013	0.001	-10000	0	-10000	0	0
CSNK1A1	0.018	0.025	-10000	0	-10000	0	0
NLK	0.011	0.004	-10000	0	-10000	0	0
CCND1	-0.043	0.28	-10000	0	-1.3	17	17
WNT1	-0.003	0.078	-10000	0	-0.45	11	11
GSK3A	0.013	0.001	-10000	0	-10000	0	0
GSK3B	0.012	0.001	-10000	0	-10000	0	0
FRAT1	0.007	0.049	-10000	0	-0.54	3	3
PPP2R5D	0.079	0.092	0.24	81	-10000	0	81
APC	0.025	0.049	-10000	0	-0.47	1	1
WNT1/LRP6/FZD1	0.1	0.09	0.23	87	-10000	0	87
CREBBP	0.017	0.021	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0.009	0.021	-9999	-0.39	1	1
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.001	0.069	-9999	-0.31	17	17
STXBP1	-0.006	0.098	-9999	-0.52	13	13
ACh/CHRNA1	-0.066	0.14	-9999	-0.33	74	74
RAB3GAP2/RIMS1/UNC13B	0.009	0.058	-9999	-0.26	17	17
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	-0.014	0.096	-9999	-0.45	17	17
mol:ACh	-0.013	0.041	-9999	-0.12	28	28
RAB3GAP2	0.012	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.035	0.072	-9999	-0.31	10	10
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.066	0.14	-9999	-0.33	74	74
UNC13B	0.012	0	-9999	-10000	0	0
CHRNA1	-0.089	0.2	-9999	-0.49	74	74
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.078	0.14	-9999	-0.33	88	88
SNAP25	-0.039	0.092	-9999	-0.21	79	79
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.11	0.22	-9999	-0.49	88	88
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.004	0.063	-9999	-0.31	14	14
STX1A/SNAP25 fragment 1/VAMP2	-0.035	0.072	-9999	-0.31	10	10

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.039	0.28	-10000	0	-0.83	35	35
NCK1/PAK1/Dok-R	-0.052	0.12	-10000	0	-0.4	35	35
NCK1/Dok-R	-0.057	0.3	-10000	0	-0.95	34	34
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
mol:beta2-estradiol	0.011	0.063	0.24	24	-10000	0	24
RELA	0.012	0	-10000	0	-10000	0	0
SHC1	0.013	0.002	-10000	0	-10000	0	0
Rac/GDP	0.009	0	-10000	0	-10000	0	0
F2	-0.022	0.15	0.24	22	-0.46	32	54
TNIP2	0.012	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.052	0.28	-10000	0	-0.9	34	34
FN1	-0.02	0.12	-10000	0	-0.47	25	25
PLD2	-0.06	0.31	-10000	0	-0.99	34	34
PTPN11	0.012	0	-10000	0	-10000	0	0
GRB14	-0.11	0.22	-10000	0	-0.5	85	85
ELK1	-0.046	0.28	-10000	0	-0.9	34	34
GRB7	-0.014	0.11	-10000	0	-0.47	20	20
PAK1	0.012	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.07	0.3	-10000	0	-0.95	35	35
CDKN1A	-0.022	0.25	-10000	0	-0.73	28	28
ITGA5	0.01	0.037	-10000	0	-0.5	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.057	0.3	-10000	0	-0.95	34	34
CRK	0.012	0	-10000	0	-10000	0	0
mol:NO	-0.019	0.22	-10000	0	-0.62	35	35
PLG	-0.1	0.32	-10000	0	-1	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.033	0.26	-10000	0	-0.8	35	35
GRB2	0.012	0	-10000	0	-10000	0	0
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
ANGPT2	-0.009	0.18	-10000	0	-1	6	6
BMX	-0.099	0.32	-10000	0	-1	35	35
ANGPT1	-0.077	0.31	-10000	0	-1.2	25	25
tube development	-0.015	0.23	-10000	0	-0.63	33	33
ANGPT4	-0.011	0.088	-10000	0	-0.45	14	14
response to hypoxia	-0.005	0.021	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.12	0.33	-10000	0	-1.1	36	36
alpha5/beta1 Integrin	0.016	0.027	-10000	0	-0.35	2	2
FGF2	-0.027	0.14	-10000	0	-0.5	28	28
STAT5A (dimer)	-0.024	0.27	-10000	0	-0.86	19	19
mol:L-citrulline	-0.019	0.22	-10000	0	-0.62	35	35
AGTR1	-0.003	0.071	-10000	0	-0.45	9	9
MAPK14	-0.055	0.31	-10000	0	-0.99	34	34
Tie2/SHP2	-0.018	0.19	-10000	0	-1.1	10	10
TEK	-0.024	0.21	-10000	0	-1.1	11	11
RPS6KB1	-0.034	0.26	-10000	0	-0.8	35	35
Angiotensin II/AT1	0	0.051	-10000	0	-0.32	9	9
Tie2/Ang1/GRB2	-0.062	0.31	-10000	0	-1	34	34
MAPK3	-0.05	0.29	-10000	0	-0.92	34	34
MAPK1	-0.05	0.29	-10000	0	-0.92	34	34
Tie2/Ang1/GRB7	-0.074	0.32	-10000	0	-1	34	34
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	-0.061	0.31	-10000	0	-0.99	34	34
PI3K	-0.051	0.31	-10000	0	-0.94	35	35
FES	-0.057	0.31	-10000	0	-0.97	35	35
Crk/Dok-R	-0.057	0.3	-10000	0	-0.95	34	34
Tie2/Ang1/ABIN2	-0.062	0.31	-10000	0	-1	34	34
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.031	0.25	-10000	0	-0.74	35	35
STAT5A	0.011	0.024	-10000	0	-0.45	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.033	0.26	-10000	0	-0.8	35	35
Tie2/Ang2	-0.039	0.29	-10000	0	-0.85	33	33
Tie2/Ang1	-0.07	0.33	-10000	0	-1.1	34	34
FOXO1	-0.031	0.26	-10000	0	-0.74	37	37
ELF1	0.016	0.019	-10000	0	-10000	0	0
ELF2	-0.062	0.3	-10000	0	-0.98	34	34
mol:Choline	-0.056	0.3	-10000	0	-0.95	34	34
cell migration	-0.033	0.069	-10000	0	-0.23	35	35
FYN	-0.022	0.25	-10000	0	-0.72	33	33
DOK2	0	0.078	-10000	0	-0.49	9	9
negative regulation of cell cycle	-0.015	0.23	-10000	0	-0.65	28	28
ETS1	0	0.068	-10000	0	-0.23	24	24
PXN	-0.017	0.23	-10000	0	-0.66	35	35
ITGB1	0.012	0	-10000	0	-10000	0	0
NOS3	-0.027	0.24	-10000	0	-0.71	35	35
RAC1	0.012	0	-10000	0	-10000	0	0
TNF	-0.08	0.19	-10000	0	-0.49	61	61
MAPKKK cascade	-0.056	0.3	-10000	0	-0.95	34	34
RASA1	0.012	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.061	0.32	-10000	0	-1	34	34
NCK1	0.012	0	-10000	0	-10000	0	0
vasculogenesis	-0.013	0.2	-10000	0	-0.56	35	35
mol:Phosphatidic acid	-0.056	0.3	-10000	0	-0.95	34	34
mol:Angiotensin II	0.001	0.005	-10000	0	-10000	0	0
mol:NADP	-0.019	0.22	-10000	0	-0.62	35	35
Rac1/GTP	-0.089	0.22	-10000	0	-0.74	35	35
MMP2	-0.085	0.32	-10000	0	-1	35	35

×

LPA4-mediated signaling events

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
ADCY4	0.009	0.047	-9999	-0.28	9	9
ADCY5	-0.038	0.12	-9999	-0.31	61	61
ADCY6	0.014	0.025	-9999	-0.33	2	2
ADCY7	0.013	0.029	-9999	-0.31	3	3
ADCY1	-0.042	0.12	-9999	-0.29	71	71
ADCY2	-0.034	0.12	-9999	-0.3	59	59
ADCY3	0.015	0.018	-9999	-0.33	1	1
ADCY8	-0.002	0.057	-9999	-0.27	16	16
PRKCE	0.009	0.021	-9999	-0.39	1	1
ADCY9	-0.001	0.071	-9999	-0.29	21	21
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.028	0.076	-9999	-0.27	12	12

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.014	0.04	-9999	-10000	0	0
VDR	0.006	0.057	-9999	-0.54	4	4
FAM120B	0.012	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.042	0.14	-9999	-0.43	20	20
RXRs/LXRs/DNA/Oxysterols	-0.048	0.17	-9999	-0.45	43	43
MED1	0.012	0	-9999	-10000	0	0
mol:9cRA	-0.002	0.018	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.033	0.12	-9999	-0.26	73	73
RXRs/NUR77	-0.057	0.15	-9999	-0.33	55	55
RXRs/PPAR	-0.073	0.14	-9999	-0.37	34	34
NCOR2	0.012	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.005	0.041	-9999	-0.39	4	4
RARs/VDR/DNA/Vit D3	0.012	0.067	-9999	-0.27	14	14
RARA	0.012	0	-9999	-10000	0	0
NCOA1	0.012	0	-9999	-10000	0	0
VDR/VDR/DNA	0.006	0.057	-9999	-0.54	4	4
RARs/RARs/DNA/9cRA	0.007	0.06	-9999	-0.25	19	19
RARG	0.007	0.053	-9999	-0.5	4	4
RPS6KB1	0.023	0.047	-9999	-0.52	1	1
RARs/THRs/DNA/SMRT	-0.033	0.12	-9999	-0.26	73	73
THRA	0.008	0.044	-9999	-0.48	3	3
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.005	0.041	-9999	-0.39	4	4
RXRs/PPAR/9cRA/PGJ2/DNA	-0.054	0.14	-9999	-0.32	53	53
NR1H4	-0.018	0.095	-9999	-0.45	17	17
RXRs/LXRs/DNA	-0.038	0.14	-9999	-0.4	18	18
NR1H2	0.012	0.014	-9999	-10000	0	0
NR1H3	0.01	0.028	-9999	-0.44	1	1
RXRs/VDR/DNA/Vit D3	-0.044	0.13	-9999	-0.35	20	20
NR4A1	-0.014	0.11	-9999	-0.46	21	21
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.036	0.1	-9999	-0.32	19	19
RXRG	-0.12	0.22	-9999	-0.5	92	92
RXR alpha/CCPG	0.017	0.024	-9999	-0.4	1	1
RXRA	0.01	0.032	-9999	-0.55	1	1
RXRB	0.011	0.016	-9999	-10000	0	0
THRB	-0.1	0.22	-9999	-0.53	77	77
PPARG	-0.095	0.21	-9999	-0.51	76	76
PPARD	0.012	0	-9999	-10000	0	0
TNF	-0.1	0.31	-9999	-0.97	35	35
mol:Oxysterols	-0.002	0.016	-9999	-10000	0	0
cholesterol transport	-0.047	0.17	-9999	-0.44	43	43
PPARA	0.009	0.04	-9999	-0.54	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.008	0.1	-9999	-0.5	15	15
RXRs/NUR77/BCL2	-0.053	0.14	-9999	-0.32	59	59
SREBF1	-0.038	0.17	-9999	-0.57	15	15
RXRs/RXRs/DNA/9cRA	-0.053	0.14	-9999	-0.32	53	53
ABCA1	-0.053	0.22	-9999	-0.78	20	20
RARs/THRs	-0.04	0.14	-9999	-0.29	73	73
RXRs/FXR	-0.06	0.15	-9999	-0.35	46	46
BCL2	-0.015	0.12	-9999	-0.52	19	19

×

Thromboxane A2 receptor signaling

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
TGM2	-0.013	0.11	-10000	0	-0.49	18	18
GNB1/GNG2	-0.052	0.068	-10000	0	-0.2	41	41
AKT1	-0.026	0.092	-10000	0	-0.23	8	8
EGF	-0.065	0.18	-10000	0	-0.48	57	57
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.009	0.078	-10000	0	-0.37	5	5
mol:Ca2+	-0.052	0.13	-10000	0	-0.3	51	51
LYN	0.014	0.067	-10000	0	-0.39	2	2
RhoA/GTP	-0.031	0.045	-10000	0	-0.14	8	8
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.061	0.15	-10000	0	-0.35	51	51
GNG2	-0.002	0.084	-10000	0	-0.48	11	11
ARRB2	0.012	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0	0.12	-10000	0	-0.42	19	19
G beta5/gamma2	-0.064	0.091	-10000	0	-0.26	40	40
PRKCH	-0.058	0.15	-10000	0	-0.35	48	48
DNM1	-0.012	0.11	-10000	0	-0.48	18	18
TXA2/TP beta/beta Arrestin3	-0.011	0.038	-10000	0	-0.22	7	7
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.029	0.14	-10000	0	-0.52	28	28
G12 family/GTP	-0.077	0.11	-10000	0	-0.31	50	50
ADRBK1	0.011	0.024	-10000	0	-0.45	1	1
ADRBK2	0.003	0.07	-10000	0	-0.54	6	6
RhoA/GTP/ROCK1	0.016	0.001	-10000	0	-10000	0	0
mol:GDP	0.032	0.099	0.33	16	-10000	0	16
mol:NADP	0.002	0.071	-10000	0	-0.47	8	8
RAB11A	0.012	0	-10000	0	-10000	0	0
PRKG1	-0.033	0.15	-10000	0	-0.51	32	32
mol:IP3	-0.067	0.16	-10000	0	-0.38	51	51
cell morphogenesis	0.016	0.001	-10000	0	-10000	0	0
PLCB2	-0.094	0.21	-10000	0	-0.52	51	51
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.024	0.1	-10000	0	-0.36	13	13
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.006	0.085	-10000	0	-0.38	8	8
RHOA	0.012	0	-10000	0	-10000	0	0
PTGIR	0.005	0.058	-10000	0	-0.49	5	5
PRKCB1	-0.065	0.15	-10000	0	-0.38	49	49
GNAQ	0.011	0.029	-10000	0	-0.54	1	1
mol:L-citrulline	0.002	0.071	-10000	0	-0.47	8	8
TXA2/TXA2-R family	-0.098	0.21	-10000	0	-0.53	53	53
LCK	0.003	0.084	-10000	0	-0.37	5	5
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.004	0.064	-10000	0	-0.45	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.019	0.03	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.013	0.065	-10000	0	-0.45	1	1
MAPK14	-0.034	0.1	-10000	0	-0.24	33	33
TGM2/GTP	-0.082	0.18	-10000	0	-0.44	54	54
MAPK11	-0.036	0.1	-10000	0	-0.24	38	38
ARHGEF1	-0.025	0.08	-10000	0	-0.19	23	23
GNAI2	0.012	0	-10000	0	-10000	0	0
JNK cascade	-0.07	0.16	-10000	0	-0.39	53	53
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.047	0.12	-10000	0	-0.29	49	49
cAMP biosynthetic process	-0.07	0.15	-10000	0	-0.36	54	54
Gq family/GTP/EBP50	0.003	0.08	-10000	0	-0.31	17	17
actin cytoskeleton reorganization	0.016	0.001	-10000	0	-10000	0	0
SRC	0.014	0.064	-10000	0	-0.35	1	1
GNB5	0.006	0.057	-10000	0	-0.54	4	4
GNB1	0.012	0	-10000	0	-10000	0	0
EGF/EGFR	-0.008	0.091	-10000	0	-0.31	12	12
VCAM1	-0.061	0.14	-10000	0	-0.35	52	52
TP beta/Gq family/GDP/G beta5/gamma2	0	0.12	-10000	0	-0.42	19	19
platelet activation	-0.046	0.14	-10000	0	-0.3	49	49
PGI2/IP	0.004	0.042	-10000	0	-0.35	5	5
PRKACA	-0.005	0.073	-10000	0	-0.26	25	25
Gq family/GDP/G beta5/gamma2	-0.001	0.11	-10000	0	-0.4	19	19
TXA2/TP beta/beta Arrestin2	-0.015	0.068	-10000	0	-0.5	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.001	0.073	-10000	0	-0.25	25	25
mol:DAG	-0.073	0.17	-10000	0	-0.42	50	50
EGFR	-0.004	0.092	-10000	0	-0.53	11	11
TXA2/TP alpha	-0.095	0.2	-10000	0	-0.49	54	54
Gq family/GTP	-0.014	0.066	-10000	0	-0.25	23	23
YES1	0.015	0.063	-10000	0	-0.35	1	1
GNAI2/GTP	-0.019	0.058	-10000	0	-0.41	1	1
PGD2/DP	-0.021	0.1	-10000	0	-0.38	28	28
SLC9A3R1	0.005	0.06	-10000	0	-0.5	5	5
FYN	0.015	0.063	-10000	0	-0.35	1	1
mol:NO	0.002	0.071	-10000	0	-0.47	8	8
GNA15	-0.005	0.093	-10000	0	-0.51	12	12
PGK/cGMP	-0.018	0.1	-10000	0	-0.31	39	39
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.002	0.092	-10000	0	-0.41	4	4
NOS3	0.002	0.071	-10000	0	-0.47	8	8
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	-0.064	0.15	-10000	0	-0.37	49	49
PRKCB	-0.065	0.16	-10000	0	-0.37	54	54
PRKCE	-0.054	0.14	-10000	0	-0.36	42	42
PRKCD	-0.061	0.16	-10000	0	-0.38	50	50
PRKCG	-0.093	0.18	-10000	0	-0.42	54	54
muscle contraction	-0.092	0.2	-10000	0	-0.5	53	53
PRKCZ	-0.058	0.15	-10000	0	-0.35	49	49
ARR3	0.003	0.034	-10000	0	-0.45	2	2
TXA2/TP beta	0.004	0.074	-10000	0	-0.46	1	1
PRKCQ	-0.084	0.17	-10000	0	-0.39	55	55
MAPKKK cascade	-0.086	0.19	-10000	0	-0.46	53	53
SELE	-0.063	0.15	-10000	0	-0.35	53	53
TP beta/GNAI2/GDP/G beta/gamma	0.014	0.075	-10000	0	-0.44	1	1
ROCK1	0.012	0	-10000	0	-10000	0	0
GNA14	-0.003	0.089	-10000	0	-0.54	10	10
chemotaxis	-0.11	0.24	-10000	0	-0.61	50	50
GNA12	0.012	0	-10000	0	-10000	0	0
GNA13	0.012	0	-10000	0	-10000	0	0
GNA11	-0.001	0.082	-10000	0	-0.52	9	9
Rac1/GTP	0.008	0.003	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0	-10000	0	-10000	0	0
HDAC3	0.012	0	-10000	0	-10000	0	0
VDR	0.006	0.057	-10000	0	-0.54	4	4
Cbp/p300/PCAF	0.018	0.05	-10000	0	-0.32	8	8
EP300	0.012	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0	0.075	-10000	0	-0.35	8	8
KAT2B	0	0.08	-10000	0	-0.54	8	8
MAPK14	0.012	0	-10000	0	-10000	0	0
AKT1	0.006	0.094	0.21	29	-0.28	11	40
RAR alpha/9cRA/Cyclin H	-0.054	0.096	-10000	0	-0.47	8	8
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.004	0.083	-10000	0	-0.36	11	11
CDC2	0	0.002	-10000	0	-10000	0	0
response to UV	0	0.003	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.038	0.096	-10000	0	-0.4	10	10
NCOR2	0.012	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.005	0.041	-10000	0	-0.39	4	4
RXRs/RARs/NRIP1/9cRA	-0.082	0.21	-10000	0	-0.52	54	54
NCOA2	-0.008	0.1	-10000	0	-0.52	14	14
NCOA3	0.012	0	-10000	0	-10000	0	0
NCOA1	0.012	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.006	0.057	-10000	0	-0.54	4	4
RARG	0.007	0.053	-10000	0	-0.5	4	4
RAR gamma1/9cRA	0.014	0.033	-10000	0	-0.3	4	4
MAPK3	0.011	0.024	-10000	0	-0.45	1	1
MAPK1	0.011	0.024	-10000	0	-0.45	1	1
MAPK8	0.01	0.041	-10000	0	-0.55	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.094	0.2	-10000	0	-0.48	59	59
RARA	-0.046	0.11	-10000	0	-0.27	56	56
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.012	0.095	-10000	0	-0.35	15	15
PRKCA	-0.011	0.11	-10000	0	-0.53	17	17
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.098	0.22	-10000	0	-0.53	59	59
RXRG	-0.14	0.2	-10000	0	-0.4	105	105
RXRA	-0.037	0.1	-10000	0	-0.3	21	21
RXRB	-0.072	0.15	-10000	0	-0.36	55	55
VDR/Vit D3/DNA	0.005	0.041	-10000	0	-0.39	4	4
RBP1	-0.076	0.2	-10000	0	-0.52	61	61
CRBP1/9-cic-RA	-0.055	0.14	-10000	0	-0.38	61	61
RARB	-0.007	0.1	-10000	0	-0.5	15	15
PRKCG	-0.14	0.23	-10000	0	-0.48	116	116
MNAT1	0.012	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.07	0.21	-10000	0	-0.5	54	54
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.062	0.18	-10000	0	-0.42	53	53
proteasomal ubiquitin-dependent protein catabolic process	-0.02	0.1	-10000	0	-0.36	17	17
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.098	0.22	-10000	0	-0.53	59	59
positive regulation of DNA binding	-0.051	0.091	-10000	0	-0.44	8	8
NRIP1	-0.1	0.26	-10000	0	-0.94	22	22
RXRs/RARs	-0.099	0.21	-10000	0	-0.5	61	61
RXRs/RXRs/DNA/9cRA	-0.1	0.2	-10000	0	-0.49	60	60
PRKACA	0.012	0	-10000	0	-10000	0	0
CDK7	0.011	0.029	-10000	0	-0.54	1	1
TFIIH	0.024	0.018	-10000	0	-0.32	1	1
RAR alpha/9cRA	-0.035	0.064	-10000	0	-0.35	6	6
CCNH	0.012	0	-10000	0	-10000	0	0
CREBBP	0.012	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.003	0.025	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.012	0.069	-10000	0	-0.58	4	4
HDAC1	0.011	0.009	-10000	0	-10000	0	0
AES	0.011	0.029	-10000	0	-0.54	1	1
FBXW11	0.012	0	-10000	0	-10000	0	0
DTX1	-0.008	0.1	-10000	0	-0.52	14	14
LRP6/FZD1	0.015	0.032	-10000	0	-0.34	3	3
TLE1	0.009	0.04	-10000	0	-0.54	2	2
AP1	-0.03	0.09	-10000	0	-0.28	19	19
NCSTN	0.012	0	-10000	0	-10000	0	0
ADAM10	0.006	0.057	-10000	0	-0.54	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.021	0.12	-10000	0	-0.46	10	10
NICD/RBPSUH	0.021	0.065	-10000	0	-0.56	4	4
WIF1	-0.25	0.25	-10000	0	-0.49	193	193
NOTCH1	-0.008	0.064	-10000	0	-0.6	4	4
PSENEN	0.011	0.029	-10000	0	-0.54	1	1
KREMEN2	-0.053	0.17	-10000	0	-0.48	49	49
DKK1	-0.18	0.24	-10000	0	-0.48	142	142
beta catenin/beta TrCP1	0.033	0.06	0.21	3	-0.3	1	4
APH1B	0.006	0.057	-10000	0	-0.54	4	4
APH1A	0.011	0.024	-10000	0	-0.45	1	1
AXIN1	-0.006	0.038	0.25	3	-0.24	2	5
CtBP/CBP/TCF1/TLE1/AES	-0.026	0.11	0.22	1	-0.5	2	3
PSEN1	0.012	0	-10000	0	-10000	0	0
FOS	-0.019	0.12	-10000	0	-0.47	24	24
JUN	0.01	0.037	-10000	0	-0.5	2	2
MAP3K7	0.012	0.004	-10000	0	-10000	0	0
CTNNB1	0.028	0.064	0.2	7	-0.32	1	8
MAPK3	0.011	0.024	-10000	0	-0.45	1	1
DKK2/LRP6/Kremen 2	-0.075	0.16	-10000	0	-0.32	108	108
HNF1A	-0.097	0.22	-10000	0	-0.54	74	74
CTBP1	0.012	0.003	-10000	0	-10000	0	0
MYC	-0.016	0.21	-10000	0	-1.3	9	9
NKD1	-0.093	0.2	-10000	0	-0.46	82	82
FZD1	0.008	0.044	-10000	0	-0.48	3	3
NOTCH1 precursor/Deltex homolog 1	0.011	0.087	-10000	0	-0.57	5	5
apoptosis	-0.03	0.09	-10000	0	-0.28	19	19
Delta 1/NOTCHprecursor	0.016	0.073	-10000	0	-0.56	4	4
DLL1	0.002	0.072	-10000	0	-0.51	7	7
PPARD	0.019	0.023	-10000	0	-10000	0	0
Gamma Secretase	0.032	0.037	-10000	0	-10000	0	0
APC	-0.006	0.038	0.25	3	-0.24	2	5
DVL1	-0.009	0.043	-10000	0	-0.48	1	1
CSNK2A1	0.012	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.13	0.17	-10000	0	-0.37	70	70
LRP6	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.001	-10000	0	-10000	0	0
NLK	0.014	0.01	-10000	0	-10000	0	0
CCND1	-0.036	0.27	-10000	0	-1.3	16	16
WNT1	-0.004	0.078	-10000	0	-0.45	11	11
Axin1/APC/beta catenin	0.022	0.052	0.26	3	-0.35	1	4
DKK2	-0.087	0.2	-10000	0	-0.5	72	72
NOTCH1 precursor/DVL1	-0.012	0.061	-10000	0	-0.5	5	5
GSK3B	0.012	0.001	-10000	0	-10000	0	0
FRAT1	0.008	0.049	-10000	0	-0.54	3	3
NOTCH/Deltex homolog 1	-0.017	0.082	-10000	0	-0.58	5	5
PPP2R5D	0.038	0.092	0.21	81	-10000	0	81
MAPK1	0.011	0.024	-10000	0	-0.45	1	1
WNT1/LRP6/FZD1	-0.13	0.15	-10000	0	-0.3	94	94
RBPJ	0.011	0.024	-10000	0	-0.45	1	1
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.029	0.12	-10000	0	-0.28	65	65
regulation of S phase of mitotic cell cycle	-0.025	0.11	-10000	0	-0.27	55	55
GNAO1	-0.014	0.11	-10000	0	-0.47	20	20
HRAS	0.011	0.024	-10000	0	-0.45	1	1
SHBG/T-DHT	-0.014	0.082	-10000	0	-0.33	24	24
PELP1	0.012	0.001	-10000	0	-10000	0	0
AKT1	0.009	0.017	-10000	0	-0.32	1	1
MAP2K1	-0.003	0.093	-10000	0	-0.31	3	3
T-DHT/AR	-0.048	0.14	-10000	0	-0.38	55	55
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.005	24	24
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.095	-10000	0	-0.52	12	12
mol:GDP	-0.068	0.16	-10000	0	-0.47	44	44
cell proliferation	0.003	0.11	-10000	0	-0.39	8	8
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
FOS	0.001	0.13	-10000	0	-0.56	11	11
mol:Ca2+	-0.01	0.021	-10000	0	-0.064	30	30
MAPK3	0.001	0.1	-10000	0	-0.36	4	4
MAPK1	0.007	0.056	-10000	0	-0.26	1	1
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
mol:IP3	0	0.001	-10000	0	-0.003	24	24
cAMP biosynthetic process	-0.01	0.08	-10000	0	-0.3	24	24
GNG2	-0.002	0.084	-10000	0	-0.48	11	11
potassium channel inhibitor activity	0	0.001	-10000	0	-0.003	24	24
HRAS/GTP	-0.018	0.098	-10000	0	-0.26	47	47
actin cytoskeleton reorganization	-0.015	0.058	-10000	0	-0.25	17	17
SRC	0.009	0.041	-10000	0	-0.54	2	2
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.003	24	24
PI3K	-0.004	0.079	-10000	0	-0.31	23	23
apoptosis	-0.006	0.091	0.38	8	-10000	0	8
T-DHT/AR/PELP1	-0.032	0.12	-10000	0	-0.31	55	55
HRAS/GDP	-0.064	0.15	-10000	0	-0.44	44	44
CREB1	0.005	0.096	-10000	0	-0.41	8	8
RAC1-CDC42/GTP	-0.014	0.059	-10000	0	-0.26	17	17
AR	-0.067	0.19	-10000	0	-0.52	55	55
GNB1	0.012	0	-10000	0	-10000	0	0
RAF1	-0.009	0.096	-10000	0	-0.29	4	4
RAC1-CDC42/GDP	-0.059	0.14	-10000	0	-0.42	44	44
T-DHT/AR/PELP1/Src	-0.023	0.11	-10000	0	-0.28	57	57
MAP2K2	-0.003	0.093	-10000	0	-0.31	3	3
T-DHT/AR/PELP1/Src/PI3K	-0.025	0.12	-10000	0	-0.28	55	55
GNAZ	-0.005	0.094	-10000	0	-0.52	12	12
SHBG	-0.023	0.13	-10000	0	-0.53	24	24
Gi family/GNB1/GNG2/GDP	-0.002	0.088	-10000	0	-0.33	13	13
mol:T-DHT	0	0	-10000	0	-0.002	19	19
RAC1	0.012	0	-10000	0	-10000	0	0
GNRH1	-0.006	0.078	-10000	0	-0.39	15	15
Gi family/GTP	-0.018	0.089	-10000	0	-0.25	28	28
CDC42	0.012	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.006	0.061	-9999	-0.36	8	8
NFATC2	-0.019	0.086	-9999	-0.34	22	22
NFATC3	0.002	0.03	-9999	-10000	0	0
CD40LG	-0.12	0.26	-9999	-0.61	51	51
PTGS2	-0.16	0.29	-9999	-0.58	84	84
JUNB	0.006	0.057	-9999	-0.54	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.017	-9999	-10000	0	0
CaM/Ca2+	-0.003	0.017	-9999	-10000	0	0
CALM1	0.008	0.009	-9999	-10000	0	0
JUN	0.005	0.039	-9999	-0.51	2	2
mol:Ca2+	-0.008	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.006	0.006	-9999	-10000	0	0
FOSL1	-0.024	0.13	-9999	-0.49	27	27
CREM	0.012	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.055	0.16	-9999	-0.42	27	27
FOS	-0.024	0.12	-9999	-0.47	24	24
IFNG	-0.12	0.25	-9999	-0.59	53	53
AP-1/NFAT1-c-4	-0.12	0.26	-9999	-0.61	50	50
FASLG	-0.13	0.27	-9999	-0.66	49	49
NFAT1-c-4/ICER1	-0.036	0.1	-9999	-0.35	18	18
IL2RA	-0.12	0.25	-9999	-0.63	40	40
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSF2	-0.11	0.23	-9999	-0.62	28	28
JunB/Fra1/NFAT1-c-4	-0.04	0.13	-9999	-0.36	28	28
IL4	-0.11	0.22	-9999	-0.59	29	29
IL2	-0.019	0.074	-9999	-0.37	15	15
IL3	-0.019	0.031	-9999	-10000	0	0
FKBP1A	0.012	0	-9999	-10000	0	0
BATF3	-0.005	0.092	-9999	-0.48	13	13
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.071	-9999	-0.45	9	9

×

Coregulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.005	0.089	-9999	-0.54	10	10
SVIL	-0.003	0.085	-9999	-0.54	9	9
ZNF318	0.019	0.025	-9999	-10000	0	0
JMJD2C	-0.004	0.029	-9999	-0.086	40	40
T-DHT/AR/Ubc9	-0.043	0.13	-9999	-0.34	56	56
CARM1	0.012	0.001	-9999	-10000	0	0
PRDX1	0.013	0.002	-9999	-10000	0	0
PELP1	0.013	0.004	-9999	-10000	0	0
CTNNB1	0.009	0.029	-9999	-0.54	1	1
AKT1	0.013	0.025	-9999	-0.45	1	1
PTK2B	0.008	0.041	-9999	-0.54	2	2
MED1	0.014	0.008	-9999	-10000	0	0
MAK	-0.031	0.15	-9999	-0.49	37	37
response to oxidative stress	0	0.002	-9999	-10000	0	0
HIP1	0.007	0.041	-9999	-0.54	2	2
GSN	0.008	0.031	-9999	-0.54	1	1
NCOA2	-0.008	0.1	-9999	-0.52	14	14
NCOA6	0.011	0.008	-9999	-10000	0	0
DNA-PK	0.029	0.036	-9999	-0.32	2	2
NCOA4	0.011	0.024	-9999	-0.45	1	1
PIAS3	0.011	0.008	-9999	-10000	0	0
cell proliferation	-0.052	0.16	-9999	-0.7	18	18
XRCC5	0.014	0.006	-9999	-10000	0	0
UBE3A	0.009	0.016	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.097	0.17	-9999	-0.34	109	109
FHL2	-0.023	0.19	-9999	-1.1	11	11
RANBP9	0.011	0.008	-9999	-10000	0	0
JMJD1A	-0.01	0.054	-9999	-0.13	60	60
CDK6	-0.014	0.12	-9999	-0.5	19	19
TGFB1I1	0.001	0.065	-9999	-0.46	7	7
T-DHT/AR/CyclinD1	-0.061	0.15	-9999	-0.35	71	71
XRCC6	0.014	0.006	-9999	-10000	0	0
T-DHT/AR	-0.049	0.16	-9999	-0.36	61	61
CTDSP1	0.011	0.003	-9999	-10000	0	0
CTDSP2	0.017	0.017	-9999	-10000	0	0
BRCA1	0.007	0.041	-9999	-0.54	2	2
TCF4	0.008	0.065	-9999	-0.54	5	5
CDKN2A	-0.11	0.21	-9999	-0.47	91	91
SRF	0.017	0.023	-9999	-10000	0	0
NKX3-1	-0.085	0.27	-9999	-0.76	40	40
KLK3	-0.03	0.18	-9999	-1.3	4	4
TMF1	0.011	0.003	-9999	-10000	0	0
HNRNPA1	0.015	0.009	-9999	-10000	0	0
AOF2	-0.003	0.011	-9999	-0.072	4	4
APPL1	0.021	0.032	-9999	-0.35	2	2
T-DHT/AR/Caspase 8	-0.042	0.14	-9999	-0.34	56	56
AR	-0.077	0.2	-9999	-0.54	55	55
UBA3	0.011	0.003	-9999	-10000	0	0
PATZ1	0.015	0.009	-9999	-10000	0	0
PAWR	0.011	0.003	-9999	-10000	0	0
PRKDC	0.011	0.041	-9999	-0.54	2	2
PA2G4	0.014	0.025	-9999	-0.42	1	1
UBE2I	0.012	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.037	0.12	-9999	-0.31	55	55
RPS6KA3	0.01	0.011	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.045	0.14	-9999	-0.34	57	57
LATS2	0.015	0.009	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.036	0.12	-9999	-0.31	55	55
Cyclin D3/CDK11 p58	0.01	0.002	-9999	-10000	0	0
VAV3	-0.03	0.14	-9999	-0.54	27	27
KLK2	-0.054	0.15	-9999	-0.42	40	40
CASP8	0.012	0.029	-9999	-0.54	1	1
T-DHT/AR/TIF2/CARM1	-0.044	0.14	-9999	-0.34	57	57
TMPRSS2	-0.098	0.3	-9999	-1	34	34
CCND1	-0.015	0.12	-9999	-0.52	18	18
PIAS1	0.009	0.016	-9999	-10000	0	0
mol:T-DHT	-0.01	0.03	-9999	-0.074	43	43
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.006	0.024	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.058	0.16	-9999	-0.36	70	70
CMTM2	-0.005	0.094	-9999	-0.52	12	12
SNURF	-0.075	0.19	-9999	-0.5	60	60
ZMIZ1	0.004	0.027	-9999	-10000	0	0
CCND3	0.012	0.001	-9999	-10000	0	0
TGIF1	0.015	0.009	-9999	-10000	0	0
FKBP4	0.011	0.008	-9999	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.024	0.14	-9999	-0.44	16	16
NF kappa B1 p50/RelA/I kappa B alpha	-0.002	0.13	-9999	-0.44	9	9
alphaV/beta3 Integrin/Osteopontin/Src	-0.014	0.11	-9999	-0.36	36	36
AP1	-0.037	0.18	-9999	-0.48	27	27
ILK	-0.034	0.14	-9999	-0.46	17	17
bone resorption	-0.023	0.14	-9999	-0.43	22	22
PTK2B	0.009	0.04	-9999	-0.54	2	2
PYK2/p130Cas	-0.025	0.14	-9999	-0.44	19	19
ITGAV	0.007	0.061	-9999	-0.52	5	5
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.003	0.077	-9999	-0.38	14	14
alphaV/beta3 Integrin/Osteopontin	-0.044	0.16	-9999	-0.37	54	54
MAP3K1	-0.036	0.15	-9999	-0.46	19	19
JUN	0.009	0.037	-9999	-0.49	2	2
MAPK3	-0.024	0.14	-9999	-0.44	18	18
MAPK1	-0.024	0.14	-9999	-0.44	18	18
Rac1/GDP	0.009	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.03	0.14	-9999	-0.44	19	19
ITGB3	-0.065	0.18	-9999	-0.48	60	60
NFKBIA	-0.015	0.14	-9999	-0.43	16	16
FOS	-0.019	0.12	-9999	-0.47	24	24
CD44	-0.009	0.1	-9999	-0.54	14	14
CHUK	0.012	0	-9999	-10000	0	0
PLAU	-0.024	0.2	-9999	-0.76	14	14
NF kappa B1 p50/RelA	-0.049	0.1	-9999	-0.44	9	9
BCAR1	0.011	0.029	-9999	-0.54	1	1
RELA	0.012	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.039	0.14	-9999	-0.34	63	63
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.041	0.15	-9999	-0.43	25	25
VAV3	-0.053	0.16	-9999	-0.46	28	28
MAP3K14	-0.033	0.15	-9999	-0.43	21	21
ROCK2	0.012	0	-9999	-10000	0	0
SPP1	-0.029	0.14	-9999	-0.5	32	32
RAC1	0.012	0	-9999	-10000	0	0
Rac1/GTP	-0.043	0.15	-9999	-0.43	27	27
MMP2	-0.049	0.2	-9999	-0.56	28	28

×

Signaling events mediated by PTP1B

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0.078	-10000	0	-0.49	9	9
Jak2/Leptin Receptor	-0.04	0.14	0.19	2	-0.42	31	33
PTP1B/AKT1	-0.004	0.078	-10000	0	-0.3	10	10
FYN	0.011	0.024	-10000	0	-0.45	1	1
p210 bcr-abl/PTP1B	-0.01	0.085	0.18	4	-0.32	14	18
EGFR	-0.005	0.094	-10000	0	-0.54	11	11
EGF/EGFR	-0.039	0.13	-10000	0	-0.36	36	36
CSF1	0.002	0.073	-10000	0	-0.53	7	7
AKT1	0.011	0.024	-10000	0	-0.45	1	1
INSR	0.012	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.08	0.16	-10000	0	-0.34	68	68
Insulin Receptor/Insulin	-0.019	0.053	-10000	0	-0.3	3	3
HCK	-0.012	0.11	-10000	0	-0.51	17	17
CRK	0.012	0	-10000	0	-10000	0	0
TYK2	-0.003	0.081	0.18	3	-0.3	13	16
EGF	-0.065	0.18	-10000	0	-0.49	57	57
YES1	0.011	0.029	-10000	0	-0.54	1	1
CAV1	-0.009	0.092	0.18	4	-0.34	11	15
TXN	0.011	0.024	-10000	0	-0.45	1	1
PTP1B/IRS1/GRB2	-0.009	0.099	-10000	0	-0.34	18	18
cell migration	0.01	0.085	0.32	14	-0.18	4	18
STAT3	0.012	0.001	-10000	0	-10000	0	0
PRLR	-0.068	0.19	-10000	0	-0.52	55	55
ITGA2B	-0.039	0.15	-10000	0	-0.51	36	36
CSF1R	-0.009	0.1	-10000	0	-0.51	15	15
Prolactin Receptor/Prolactin	-0.065	0.16	-10000	0	-0.37	76	76
FGR	-0.004	0.091	-10000	0	-0.5	12	12
PTP1B/p130 Cas	-0.004	0.081	-10000	0	-0.31	12	12
Crk/p130 Cas	0.001	0.077	-10000	0	-0.34	7	7
DOK1	0	0.082	-10000	0	-0.36	8	8
JAK2	-0.042	0.14	-10000	0	-0.42	30	30
Jak2/Leptin Receptor/Leptin	-0.051	0.12	-10000	0	-0.44	23	23
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
PTPN1	-0.01	0.085	0.18	4	-0.32	14	18
LYN	0.008	0.049	-10000	0	-0.54	3	3
CDH2	-0.14	0.24	-10000	0	-0.5	111	111
SRC	0.009	0.049	-10000	0	-0.48	2	2
ITGB3	-0.068	0.18	-10000	0	-0.48	60	60
CAT1/PTP1B	-0.064	0.16	-10000	0	-0.43	35	35
CAPN1	0.011	0.029	-10000	0	-0.55	1	1
CSK	0.012	0	-10000	0	-10000	0	0
PI3K	-0.029	0.073	-10000	0	-0.32	7	7
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.047	0.12	-10000	0	-0.43	24	24
negative regulation of transcription	-0.041	0.14	-10000	0	-0.42	30	30
FCGR2A	0.004	0.066	-10000	0	-0.51	6	6
FER	0.008	0.047	-10000	0	-0.51	3	3
alphaIIb/beta3 Integrin	-0.076	0.17	-10000	0	-0.36	92	92
BLK	-0.071	0.18	-10000	0	-0.49	60	60
Insulin Receptor/Insulin/Shc	0.017	0.014	-10000	0	-0.25	1	1
RHOA	0.013	0.003	-10000	0	-10000	0	0
LEPR	0.003	0.069	-10000	0	-0.49	7	7
BCAR1	0.011	0.029	-10000	0	-0.54	1	1
p210 bcr-abl/Grb2	0.012	0	-10000	0	-10000	0	0
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.071	0.16	-10000	0	-0.46	33	33
PRL	-0.023	0.12	-10000	0	-0.45	25	25
SOCS3	-0.029	0.23	-10000	0	-1.3	11	11
SPRY2	-0.019	0.12	-10000	0	-0.51	22	22
Insulin Receptor/Insulin/IRS1	0.002	0.071	-10000	0	-0.32	17	17
CSF1/CSF1R	-0.013	0.1	-10000	0	-0.38	14	14
Ras protein signal transduction	0.015	0.025	-10000	0	-10000	0	0
IRS1	-0.011	0.11	-10000	0	-0.53	16	16
INS	0	0.024	-10000	0	-0.45	1	1
LEP	-0.007	0.078	-10000	0	-0.45	11	11
STAT5B	-0.019	0.092	-10000	0	-0.27	25	25
STAT5A	-0.019	0.092	-10000	0	-0.27	24	24
GRB2	0.012	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.009	0.094	-10000	0	-0.34	17	17
CSN2	-0.026	0.08	-10000	0	-0.52	1	1
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
LAT	-0.001	0.084	-10000	0	-0.48	9	9
YBX1	0.018	0.028	-10000	0	-0.52	1	1
LCK	-0.017	0.12	-10000	0	-0.5	21	21
SHC1	0.012	0	-10000	0	-10000	0	0
NOX4	-0.011	0.11	-10000	0	-0.51	16	16

×

FAS signaling pathway (CD95)

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
SPTAN1	0.014	0.056	0.23	19	-0.21	1	20
RFC1	0.014	0.056	0.23	19	-0.21	1	20
PRKDC	0.012	0.061	0.23	19	-0.28	3	22
RIPK1	0.013	0.002	-10000	0	-10000	0	0
CASP7	-0.012	0.068	0.24	1	-0.8	2	3
FASLG/FAS/FADD/FAF1	-0.009	0.093	0.21	26	-0.26	22	48
MAP2K4	-0.002	0.1	-10000	0	-0.36	4	4
mol:ceramide	-0.012	0.11	-10000	0	-0.31	25	25
GSN	0.013	0.059	0.24	15	-0.31	1	16
FASLG/FAS/FADD/FAF1/Caspase 8	0.002	0.1	-10000	0	-0.3	20	20
FAS	0	0.079	-10000	0	-0.53	8	8
BID	0.013	0.041	0.29	6	-0.33	1	7
MAP3K1	0.008	0.075	0.2	1	-0.52	2	3
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
RB1	0.002	0.083	0.24	15	-0.31	14	29
CFLAR	0.013	0.002	-10000	0	-10000	0	0
HGF/MET	-0.071	0.17	-10000	0	-0.34	98	98
ARHGDIB	0.013	0.057	0.24	15	-10000	0	15
FADD	0.01	0.024	-10000	0	-0.45	1	1
actin filament polymerization	-0.013	0.059	0.31	1	-0.23	19	20
NFKB1	-0.024	0.049	-10000	0	-0.27	1	1
MAPK8	-0.007	0.13	-10000	0	-0.41	17	17
DFFA	0.014	0.056	0.23	19	-0.21	1	20
DNA fragmentation during apoptosis	0.014	0.056	0.23	19	-0.21	1	20
FAS/FADD/MET	-0.014	0.11	-10000	0	-0.31	42	42
CFLAR/RIP1	0.016	0.006	-10000	0	-10000	0	0
FAIM3	0	0.081	-10000	0	-0.51	9	9
FAF1	0.012	0.006	-10000	0	-10000	0	0
PARP1	0.014	0.056	0.23	19	-0.21	1	20
DFFB	0.014	0.056	0.23	19	-0.21	1	20
CHUK	-0.02	0.042	-10000	0	-10000	0	0
FASLG	-0.047	0.16	-10000	0	-0.5	42	42
FAS/FADD	0.008	0.06	-10000	0	-0.37	9	9
HGF	-0.043	0.16	-10000	0	-0.5	40	40
LMNA	0.024	0.049	0.22	15	-10000	0	15
CASP6	0.014	0.056	0.24	15	-10000	0	15
CASP10	0.002	0.07	-10000	0	-0.5	7	7
CASP3	0.017	0.067	0.27	20	-0.25	1	21
PTPN13	-0.041	0.16	-10000	0	-0.52	37	37
CASP8	0.007	0.055	0.32	9	-0.4	1	10
IL6	-0.053	0.25	-10000	0	-1.2	14	14
MET	-0.035	0.15	-10000	0	-0.52	33	33
ICAD/CAD	0.013	0.052	0.22	15	-10000	0	15
FASLG/FAS/FADD/FAF1/Caspase 10	-0.012	0.11	-10000	0	-0.32	25	25
activation of caspase activity by cytochrome c	0.013	0.041	0.29	6	-0.33	1	7
PAK2	0.013	0.058	0.23	19	-0.23	2	21
BCL2	-0.015	0.12	-10000	0	-0.52	19	19

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.024	0.37	-9999	-1.1	15	15
PLK1	0.029	0.14	-9999	-1.2	4	4
BIRC5	-0.006	0.27	-9999	-1.4	13	13
HSPA1B	0.017	0.38	-9999	-1.1	17	17
MAP2K1	0.028	0.033	-9999	-10000	0	0
BRCA2	0.003	0.41	-9999	-1.1	23	23
FOXM1	-0.004	0.47	-9999	-1.5	18	18
XRCC1	0.024	0.37	-9999	-1.1	15	15
FOXM1B/p19	-0.16	0.32	-9999	-1.1	25	25
Cyclin D1/CDK4	-0.009	0.39	-9999	-1	24	24
CDC2	0.017	0.38	-9999	-1.1	18	18
TGFA	-0.02	0.4	-9999	-0.97	30	30
SKP2	0.024	0.37	-9999	-1.1	15	15
CCNE1	-0.011	0.11	-9999	-0.5	19	19
CKS1B	0.023	0.37	-9999	-1.1	15	15
RB1	-0.094	0.2	-9999	-0.96	13	13
FOXM1C/SP1	0.005	0.4	-9999	-1.2	19	19
AURKB	0.024	0.17	-9999	-1.4	5	5
CENPF	0.013	0.4	-9999	-1.3	17	17
CDK4	0.017	0.014	-9999	-10000	0	0
MYC	0.021	0.35	-9999	-0.96	20	20
CHEK2	0.025	0.052	-9999	-0.52	2	2
ONECUT1	-0.004	0.38	-9999	-1	22	22
CDKN2A	-0.11	0.21	-9999	-0.48	91	91
LAMA4	0.022	0.37	-9999	-1.1	16	16
FOXM1B/HNF6	-0.02	0.43	-9999	-1.2	22	22
FOS	0.007	0.39	-9999	-1.1	19	19
SP1	0.013	0.004	-9999	-10000	0	0
CDC25B	0.023	0.37	-9999	-1.1	15	15
response to radiation	0.013	0.03	-9999	-10000	0	0
CENPB	0.024	0.37	-9999	-1.1	15	15
CENPA	0.015	0.39	-9999	-1.2	17	17
NEK2	0.02	0.38	-9999	-1.2	16	16
HIST1H2BA	0.016	0.37	-9999	-1.1	15	15
CCNA2	0.007	0.066	-9999	-0.55	5	5
EP300	0.012	0	-9999	-10000	0	0
CCNB1/CDK1	0.008	0.41	-9999	-1.4	15	15
CCNB2	0.023	0.37	-9999	-1.1	16	16
CCNB1	0.019	0.38	-9999	-1.2	15	15
ETV5	-0.01	0.43	-9999	-1.2	29	29
ESR1	-0.072	0.52	-9999	-1.1	58	58
CCND1	-0.008	0.4	-9999	-1	25	25
GSK3A	0.026	0.028	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.017	0.091	-9999	-0.32	20	20
CDK2	0.015	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.015	0.035	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.13	0.3	-9999	-1.2	18	18
GAS1	-0.061	0.48	-9999	-1.1	43	43
MMP2	-0.024	0.45	-9999	-1.2	33	33
RB1/FOXM1C	-0.014	0.4	-9999	-1.1	23	23
CREBBP	0.012	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

Figure S57. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S57. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.016	0.099	-9999	-0.27	47	47
RGS9BP	-0.022	0.12	-9999	-0.45	26	26
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.008	0.07	-9999	-0.45	9	9
mol:Na +	-0.004	0.058	-9999	-0.26	17	17
mol:ADP	-0.003	0.06	-9999	-0.32	13	13
GNAT2	0.007	0.042	-9999	-0.45	3	3
RGS9-1/Gbeta5/R9AP	-0.039	0.14	-9999	-0.33	66	66
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.006	0.029	-9999	-0.27	4	4
GRK7	0.003	0.048	-9999	-0.45	4	4
CNGB3	-0.008	0.078	-9999	-0.45	11	11
Cone Metarhodopsin II/X-Arrestin	0.002	0.024	-9999	-0.32	2	2
mol:Ca2+	-0.006	0.061	-9999	-0.24	24	24
Cone PDE6	-0.031	0.12	-9999	-0.45	14	14
Cone Metarhodopsin II	-0.002	0.046	-9999	-0.24	13	13
Na + (4 Units)	-0.005	0.061	-9999	-0.23	24	24
GNAT2/GDP	-0.029	0.12	-9999	-0.35	32	32
GNB5	0.006	0.057	-9999	-0.54	4	4
mol:GMP (4 units)	0.006	0.034	-9999	-0.24	7	7
Cone Transducin	-0.016	0.1	-9999	-0.28	47	47
SLC24A2	-0.004	0.062	-9999	-0.45	7	7
GNB3/GNGT2	-0.029	0.13	-9999	-0.36	46	46
GNB3	-0.037	0.15	-9999	-0.5	35	35
GNAT2/GTP	0.005	0.03	-9999	-0.32	3	3
CNGA3	0	0.058	-9999	-0.45	6	6
ARR3	0.003	0.034	-9999	-0.45	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.004	0.058	-9999	-0.27	17	17
mol:Pi	-0.039	0.14	-9999	-0.33	66	66
Cone CNG Channel	-0.009	0.059	-9999	-0.42	3	3
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.004	0.062	-9999	-0.45	7	7
RGS9	-0.054	0.17	-9999	-0.49	49	49
PDE6C	0.001	0.041	-9999	-0.45	3	3
GNGT2	-0.004	0.091	-9999	-0.5	12	12
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.024	-9999	-0.45	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.012	0	-9999	-10000	0	0
VLDLR	-0.004	0.093	-9999	-0.54	11	11
LRPAP1	0.012	0	-9999	-10000	0	0
NUDC	0.012	0	-9999	-10000	0	0
RELN/LRP8	-0.076	0.15	-9999	-0.3	116	116
CaM/Ca2+	0.009	0	-9999	-10000	0	0
KATNA1	0.012	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.063	0.14	-9999	-0.3	57	57
IQGAP1/CaM	0.018	0	-9999	-10000	0	0
DAB1	-0.03	0.13	-9999	-0.45	31	31
IQGAP1	0.012	0	-9999	-10000	0	0
PLA2G7	-0.018	0.12	-9999	-0.49	22	22
CALM1	0.012	0	-9999	-10000	0	0
DYNLT1	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.013	0.045	-9999	-0.34	6	6
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0	-9999	-10000	0	0
CDK5R1	0.001	0.074	-9999	-0.5	8	8
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.033	0.13	-9999	-0.45	33	33
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.17	-9999	-0.31	142	142
YWHAE	0.012	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.042	0.12	-9999	-0.38	6	6
MAP1B	-0.021	0.072	-9999	-0.29	21	21
RAC1	0.019	0	-9999	-10000	0	0
p35/CDK5	-0.048	0.12	-9999	-0.42	5	5
RELN	-0.14	0.23	-9999	-0.49	114	114
PAFAH/LIS1	0.005	0.073	-9999	-0.28	22	22
LIS1/CLIP170	0.024	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.054	0.075	-9999	-0.33	3	3
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.051	0.11	-9999	-0.24	77	77
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.052	0.12	-9999	-0.35	15	15
LIS1/IQGAP1	0.024	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	0.011	0.024	-9999	-0.45	1	1
PAFAH1B2	0.009	0.04	-9999	-0.54	2	2
MAP1B/LIS1/Dynein heavy chain	0.008	0.05	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.036	0.12	-9999	-0.36	6	6
LRP8	0.004	0.062	-9999	-0.48	6	6
NDEL1/Katanin 60	-0.042	0.12	-9999	-0.38	6	6
P39/CDK5	-0.065	0.14	-9999	-0.43	14	14
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0	-9999	-10000	0	0
CDK5	-0.052	0.13	-9999	-0.45	4	4
PPP2R5D	0.012	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.02	0	-9999	-10000	0	0
CSNK2A1	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.077	0.15	-9999	-0.3	75	75
RELN/VLDLR	-0.07	0.14	-9999	-0.3	68	68
CDC42	0.019	0	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.005	0.063	-9999	0	-0.33	13	13
ARNO/beta Arrestin1-2	-0.016	0.083	-9999	0	-10000	0	0
EGFR	-0.004	0.092	-9999	0	-0.53	11	11
EPHA2	-0.003	0.088	-9999	0	-0.51	11	11
USP6	0.011	0.024	-9999	0	-0.45	1	1
IQSEC1	0.011	0.029	-9999	0	-0.54	1	1
EGFR/EGFR/EGF/EGF	-0.049	0.15	-9999	0	-0.36	65	65
ARRB2	0.006	0.018	-9999	0	-10000	0	0
mol:GTP	0.005	0.041	-9999	0	-0.17	12	12
ARRB1	0.007	0.053	-9999	0	-0.5	4	4
FBXO8	0.01	0.034	-9999	0	-0.45	2	2
TSHR	-0.04	0.14	-9999	0	-0.45	40	40
EGF	-0.065	0.18	-9999	0	-0.48	57	57
somatostatin receptor activity	0	0	-9999	0	-0.001	16	16
ARAP2	-0.009	0.1	-9999	0	-0.54	14	14
mol:GDP	-0.019	0.07	-9999	0	-0.27	10	10
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	7	7
ITGA2B	-0.038	0.15	-9999	0	-0.51	36	36
ARF6	0.012	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.016	0.068	-9999	0	-0.28	14	14
ADAP1	-0.004	0.093	-9999	0	-0.54	11	11
KIF13B	0.009	0.04	-9999	0	-0.54	2	2
HGF/MET	-0.056	0.16	-9999	0	-0.38	69	69
PXN	0.012	0	-9999	0	-10000	0	0
ARF6/GTP	-0.024	0.082	-9999	0	-0.27	14	14
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.033	0.13	-9999	0	-0.34	33	33
ADRB2	-0.064	0.18	-9999	0	-0.48	57	57
receptor agonist activity	0	0	-9999	0	0	18	18
actin filament binding	0	0	-9999	0	-0.001	16	16
SRC	0.009	0.04	-9999	0	-0.54	2	2
ITGB3	-0.068	0.18	-9999	0	-0.48	60	60
GNAQ	0.011	0.029	-9999	0	-0.54	1	1
EFA6/PI-4-5-P2	0	0	-9999	0	-0.001	10	10
ARF6/GDP	0.012	0.077	-9999	0	-0.4	5	5
ARF6/GDP/GULP/ACAP1	-0.026	0.12	-9999	0	-0.38	26	26
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.042	0.13	-9999	0	-0.3	44	44
ACAP1	-0.001	0.08	-9999	0	-0.48	10	10
ACAP2	0.011	0.029	-9999	0	-0.54	1	1
LHCGR/beta Arrestin2	-0.001	0.024	-9999	0	-0.26	3	3
EFNA1	-0.001	0.082	-9999	0	-0.52	9	9
HGF	-0.043	0.16	-9999	0	-0.5	40	40
CYTH3	0.009	0.017	-9999	0	-0.32	1	1
CYTH2	0.009	0.001	-9999	0	-10000	0	0
NCK1	0.012	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	17	17
endosomal lumen acidification	0	0	0	1	0	16	17
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.032	0.15	-9999	0	-0.54	30	30
GNAQ/ARNO	0.014	0.015	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	2	2
MET	-0.035	0.15	-9999	0	-0.52	33	33
GNA14	-0.003	0.089	-9999	0	-0.54	10	10
GNA15	-0.005	0.093	-9999	0	-0.51	12	12
GIT1	0.012	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	10	10
GNA11	-0.001	0.082	-9999	0	-0.52	9	9
LHCGR	-0.003	0.041	-9999	0	-0.45	3	3
AGTR1	-0.003	0.071	-9999	0	-0.45	9	9
desensitization of G-protein coupled receptor protein signaling pathway	-0.001	0.024	-9999	0	-0.26	3	3
IPCEF1/ARNO	-0.023	0.097	-9999	0	-0.44	3	3
alphaIIb/beta3 Integrin	-0.075	0.17	-9999	0	-0.36	92	92

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.01	0.037	-10000	0	-0.5	2	2
LAT2	-0.018	0.11	-10000	0	-0.38	15	15
AP1	-0.058	0.13	-10000	0	-0.46	23	23
mol:PIP3	-0.023	0.15	-10000	0	-0.48	21	21
IKBKB	-0.005	0.091	0.15	1	-0.28	17	18
AKT1	-0.022	0.12	-10000	0	-0.39	15	15
IKBKG	-0.005	0.091	0.15	2	-0.27	20	22
MS4A2	-0.018	0.11	-10000	0	-0.46	21	21
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
MAP3K1	-0.007	0.12	-10000	0	-0.42	16	16
mol:Ca2+	-0.014	0.12	-10000	0	-0.35	21	21
LYN	0.007	0.05	-10000	0	-0.55	3	3
CBLB	-0.016	0.1	-10000	0	-0.36	15	15
SHC1	0.012	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.016	0.043	-10000	0	-0.23	11	11
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.002	0.088	-10000	0	-0.53	10	10
PLD2	-0.031	0.12	-10000	0	-0.31	39	39
PTPN13	-0.032	0.13	-10000	0	-0.4	21	21
PTPN11	0.011	0.007	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.001	0.1	-10000	0	-0.29	13	13
SYK	0	0.08	-10000	0	-0.54	8	8
GRB2	0.012	0	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.065	0.14	-10000	0	-0.5	21	21
LAT	-0.022	0.11	-10000	0	-0.37	20	20
PAK2	-0.014	0.13	-10000	0	-0.44	18	18
NFATC2	-0.048	0.12	-10000	0	-0.51	21	21
HRAS	-0.021	0.14	-10000	0	-0.44	23	23
GAB2	0.01	0.034	-10000	0	-0.45	2	2
PLA2G1B	0.025	0.015	-10000	0	-10000	0	0
Fc epsilon R1	-0.056	0.15	-10000	0	-0.32	80	80
Antigen/IgE/Fc epsilon R1	-0.049	0.14	-10000	0	-0.29	80	80
mol:GDP	-0.03	0.15	-10000	0	-0.47	26	26
JUN	0.01	0.037	-10000	0	-0.5	2	2
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
FOS	-0.019	0.12	-10000	0	-0.47	24	24
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.024	0.11	-10000	0	-0.34	21	21
CHUK	-0.005	0.091	0.15	1	-0.28	17	18
KLRG1	-0.023	0.11	-10000	0	-0.37	16	16
VAV1	-0.027	0.12	-10000	0	-0.38	25	25
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.016	0.1	-10000	0	-0.35	16	16
negative regulation of mast cell degranulation	-0.022	0.12	-10000	0	-0.4	19	19
BTK	-0.033	0.16	-10000	0	-0.54	23	23
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.035	0.14	-10000	0	-0.32	53	53
GAB2/PI3K/SHP2	-0.061	0.11	-10000	0	-0.43	14	14
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.024	0.11	-10000	0	-0.32	26	26
RAF1	0.015	0.019	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.053	0.16	-10000	0	-0.37	58	58
FCER1G	-0.005	0.094	-10000	0	-0.52	12	12
FCER1A	-0.068	0.19	-10000	0	-0.51	56	56
Antigen/IgE/Fc epsilon R1/Fyn	-0.039	0.13	-10000	0	-0.31	47	47
MAPK3	0.023	0.016	-10000	0	-10000	0	0
MAPK1	0.023	0.016	-10000	0	-10000	0	0
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	0.008	0.067	-10000	0	-0.5	4	4
DUSP1	-0.001	0.079	-10000	0	-0.45	11	11
NF-kappa-B/RelA	-0.022	0.043	-10000	0	-0.21	2	2
actin cytoskeleton reorganization	-0.013	0.1	-10000	0	-0.38	12	12
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.06	0.12	-10000	0	-0.48	18	18
FER	-0.018	0.1	-10000	0	-0.34	18	18
RELA	0.012	0	-10000	0	-10000	0	0
ITK	-0.035	0.1	-10000	0	-0.37	26	26
SOS1	0.012	0	-10000	0	-10000	0	0
PLCG1	-0.025	0.15	-10000	0	-0.49	22	22
cytokine secretion	-0.016	0.031	-10000	0	-10000	0	0
SPHK1	-0.025	0.11	-10000	0	-0.33	26	26
PTK2	-0.014	0.1	-10000	0	-0.39	12	12
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.063	0.13	-10000	0	-0.51	19	19
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.019	0.14	-10000	0	-0.45	21	21
MAP2K2	0.02	0.016	-10000	0	-10000	0	0
MAP2K1	0.02	0.016	-10000	0	-10000	0	0
MAP2K7	0.012	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.021	0.1	-10000	0	-0.39	13	13
MAP2K4	0.013	0.068	-10000	0	-0.9	2	2
Fc epsilon R1/FcgammaRIIB	-0.055	0.16	-10000	0	-0.37	56	56
mol:Choline	-0.03	0.12	-10000	0	-0.31	39	39
SHC/Grb2/SOS1	-0.004	0.098	-10000	0	-0.38	9	9
FYN	0.011	0.024	-10000	0	-0.45	1	1
DOK1	0.012	0	-10000	0	-10000	0	0
PXN	-0.007	0.098	-10000	0	-0.42	7	7
HCLS1	-0.026	0.12	-10000	0	-0.37	24	24
PRKCB	-0.018	0.12	-10000	0	-0.37	23	23
FCGR2B	-0.015	0.12	-10000	0	-0.52	19	19
IGHE	-0.001	0.005	-10000	0	-10000	0	0
KLRG1/SHIP	-0.022	0.12	-10000	0	-0.41	19	19
LCP2	0	0.079	-10000	0	-0.5	9	9
PLA2G4A	-0.063	0.14	-10000	0	-0.32	62	62
RASA1	0.012	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.03	0.12	-10000	0	-0.31	39	39
IKK complex	0.009	0.072	0.15	2	-0.23	11	13
WIPF1	0.008	0.047	-10000	0	-0.51	3	3

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.027	0.11	-9999	-0.34	41	41
PRKCZ	0.009	0.04	-9999	-0.54	2	2
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.002	0.067	-9999	-0.31	6	6
IRAK/TOLLIP	-0.005	0.086	-9999	-0.28	17	17
IKBKB	0.012	0	-9999	-10000	0	0
IKBKG	0.012	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.076	0.17	-9999	-0.36	92	92
IL1A	-0.055	0.17	-9999	-0.47	51	51
IL1B	-0.019	0.13	-9999	-0.39	35	35
IRAK/TRAF6/p62/Atypical PKCs	0.009	0.082	-9999	-0.44	1	1
IL1R2	-0.052	0.17	-9999	-0.52	45	45
IL1R1	-0.001	0.083	-9999	-0.53	9	9
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.006	0.083	-9999	-0.37	6	6
TOLLIP	0.012	0	-9999	-10000	0	0
TICAM2	-0.007	0.097	-9999	-0.54	12	12
MAP3K3	0.012	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.008	0	-9999	-10000	0	0
IKK complex/ELKS	0.031	0.065	-9999	-10000	0	0
JUN	-0.001	0.09	-9999	-0.42	4	4
MAP3K7	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.018	0.13	-9999	-0.53	10	10
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.023	0.11	-9999	-0.3	25	25
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.014	0.11	-9999	-0.46	2	2
IL1 beta fragment/IL1R1/IL1RAP	-0.017	0.12	-9999	-0.34	32	32
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.006	0.094	-9999	-0.45	4	4
IRAK1	-0.014	0.095	-9999	-0.28	41	41
IL1RN/IL1R1	-0.031	0.13	-9999	-0.37	47	47
IRAK4	0.012	0	-9999	-10000	0	0
PRKCI	0.008	0.044	-9999	-0.48	3	3
TRAF6	0.012	0	-9999	-10000	0	0
PI3K	-0.006	0.093	-9999	-0.37	23	23
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.083	-9999	-0.37	6	6
CHUK	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.017	0.12	-9999	-0.34	32	32
IL1 beta/IL1R2	-0.049	0.16	-9999	-0.35	72	72
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0.075	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.046	0.1	-9999	-0.48	10	10
IRAK3	-0.023	0.13	-9999	-0.48	27	27
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.012	0.13	-9999	-0.53	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.081	-9999	-0.32	2	2
IL1 alpha/IL1R1/IL1RAP	-0.034	0.12	-9999	-0.28	70	70
RELA	0.012	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.011	0.024	-9999	-0.45	1	1
MYD88	0.012	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.003	0.082	-9999	-10000	0	0
IL1RAP	-0.004	0.09	-9999	-0.5	12	12
UBE2N	0.012	0	-9999	-10000	0	0
IRAK/TRAF6	-0.056	0.11	-9999	-0.46	16	16
CASP1	-0.01	0.1	-9999	-0.5	16	16
IL1RN/IL1R2	-0.067	0.17	-9999	-0.39	77	77
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.008	0.12	-9999	-0.32	32	32
TMEM189-UBE2V1	-0.05	0.16	-9999	-0.49	41	41
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.009	0.086	-9999	-0.34	10	10
PIK3CA	0.01	0.034	-9999	-0.45	2	2
IL1RN	-0.043	0.16	-9999	-0.5	40	40
TRAF6/TAK1/TAB1/TAB2	-0.017	0.075	-9999	-0.26	17	17
MAP2K6	-0.011	0.095	-9999	-0.47	3	3

×

IL6-mediated signaling events

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
BCL2L1	-0.072	0.21	-9999	-0.71	8	8
CRP	-0.082	0.22	-9999	-0.73	10	10
cell cycle arrest	-0.091	0.24	-9999	-0.69	20	20
TIMP1	-0.067	0.21	-9999	-0.74	12	12
IL6ST	-0.036	0.15	-9999	-0.52	33	33
Rac1/GDP	-0.049	0.15	-9999	-0.44	28	28
AP1	-0.006	0.096	-9999	-0.37	5	5
GAB2	0.01	0.034	-9999	-0.45	2	2
TNFSF11	-0.17	0.37	-9999	-1	49	49
HSP90B1	0.011	0.044	-9999	-10000	0	0
GAB1	0.011	0.029	-9999	-0.54	1	1
MAPK14	-0.046	0.18	-9999	-0.54	29	29
AKT1	0.031	0.052	-9999	-10000	0	0
FOXO1	0.035	0.051	-9999	-10000	0	0
MAP2K6	-0.054	0.16	-9999	-0.48	30	30
mol:GTP	-0.001	0.002	-9999	-10000	0	0
MAP2K4	-0.052	0.16	-9999	-0.47	22	22
MITF	-0.049	0.15	-9999	-0.44	28	28
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0	-9999	-10000	0	0
A2M	0.01	0.1	-9999	-1.3	2	2
CEBPB	0.016	0.006	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.003	0.063	-9999	-10000	0	0
STAT3	-0.095	0.25	-9999	-0.73	20	20
STAT1	-0.004	0.019	-9999	-10000	0	0
CEBPD	-0.079	0.23	-9999	-0.84	12	12
PIK3CA	0.011	0.034	-9999	-0.45	2	2
PI3K	-0.003	0.093	-9999	-0.36	23	23
JUN	0.009	0.037	-9999	-0.5	2	2
PIAS3/MITF	-0.04	0.14	-9999	-0.45	21	21
MAPK11	-0.048	0.18	-9999	-0.54	29	29
STAT3 (dimer)/FOXO1	-0.043	0.2	-9999	-0.56	13	13
GRB2/SOS1/GAB family	-0.051	0.11	-9999	-0.41	20	20
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.049	0.15	-9999	-0.42	31	31
GRB2	0.013	0.001	-9999	-10000	0	0
JAK2	-0.001	0.085	-9999	-0.54	9	9
LBP	-0.17	0.34	-9999	-0.84	59	59
PIK3R1	-0.017	0.12	-9999	-0.52	21	21
JAK1	0.004	0.065	-9999	-0.55	5	5
MYC	-0.087	0.25	-9999	-0.9	16	16
FGG	-0.083	0.22	-9999	-0.72	10	10
macrophage differentiation	-0.091	0.24	-9999	-0.69	20	20
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.05	0.16	-9999	-0.45	25	25
JUNB	-0.075	0.22	-9999	-0.71	15	15
FOS	-0.019	0.12	-9999	-0.47	24	24
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.053	0.15	-9999	-0.44	29	29
STAT1/PIAS1	-0.045	0.14	-9999	-0.4	22	22
GRB2/SOS1/GAB family/SHP2/PI3K	0.021	0.053	-9999	-10000	0	0
STAT3 (dimer)	-0.094	0.25	-9999	-0.73	20	20
PRKCD	-0.057	0.19	-9999	-0.56	17	17
IL6R	-0.021	0.13	-9999	-0.52	23	23
SOCS3	-0.053	0.24	-9999	-1	15	15
gp130 (dimer)/JAK1/JAK1/LMO4	-0.014	0.11	-9999	-0.33	37	37
Rac1/GTP	-0.053	0.16	-9999	-0.44	30	30
HCK	-0.012	0.11	-9999	-0.51	17	17
MAPKKK cascade	0.006	0.058	-9999	-10000	0	0
bone resorption	-0.15	0.34	-9999	-0.92	49	49
IRF1	-0.072	0.21	-9999	-0.67	12	12
mol:GDP	-0.056	0.16	-9999	-0.43	35	35
SOS1	0.012	0.002	-9999	-10000	0	0
VAV1	-0.056	0.16	-9999	-0.44	35	35
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.052	0.2	-9999	-0.56	36	36
PTPN11	-0.003	0.015	-9999	-10000	0	0
IL6/IL6RA	-0.049	0.15	-9999	-0.36	64	64
gp130 (dimer)/TYK2/TYK2/LMO4	-0.01	0.1	-9999	-0.32	35	35
gp130 (dimer)/JAK2/JAK2/LMO4	-0.018	0.12	-9999	-0.33	42	42
IL6	-0.047	0.16	-9999	-0.48	44	44
PIAS3	0.012	0	-9999	-10000	0	0
PTPRE	0.006	0.06	-9999	-0.45	6	6
PIAS1	0.012	0	-9999	-10000	0	0
RAC1	0.012	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.043	0.13	-9999	-0.37	28	28
LMO4	0.007	0.051	-9999	-0.55	3	3
STAT3 (dimer)/PIAS3	-0.085	0.23	-9999	-0.72	15	15
MCL1	0.036	0.048	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.016	0.11	-10000	0	-0.37	33	33
CRKL	-0.01	0.1	-10000	0	-0.37	9	9
mol:PIP3	-0.007	0.068	0.48	7	-10000	0	7
AKT1	0.007	0.048	0.34	7	-0.23	1	8
PTK2B	0.009	0.04	-10000	0	-0.54	2	2
RAPGEF1	-0.004	0.096	-10000	0	-0.37	7	7
RANBP10	0.012	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
HGF/MET/SHIP2	-0.039	0.14	-10000	0	-0.32	69	69
MAP3K5	-0.004	0.11	-10000	0	-0.42	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.029	0.13	-10000	0	-0.31	49	49
AP1	-0.014	0.088	-10000	0	-0.31	25	25
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.012	0	-10000	0	-10000	0	0
apoptosis	-0.011	0.12	-10000	0	-0.87	6	6
STAT3 (dimer)	-0.01	0.11	-10000	0	-0.47	6	6
GAB1/CRKL/SHP2/PI3K	-0.008	0.12	-10000	0	-0.41	15	15
INPP5D	-0.002	0.088	-10000	0	-0.53	10	10
CBL/CRK	-0.003	0.096	-10000	0	-0.37	7	7
PTPN11	0.012	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.012	0	-10000	0	-10000	0	0
PTEN	0.002	0.075	-10000	0	-0.54	7	7
ELK1	-0.018	0.055	-10000	0	-0.19	33	33
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.003	0.068	-10000	0	-0.28	7	7
PAK1	0.012	0.044	0.32	7	-10000	0	7
HGF/MET/RANBP10	-0.039	0.14	-10000	0	-0.34	47	47
HRAS	-0.041	0.18	-10000	0	-0.62	28	28
DOCK1	-0.004	0.096	-10000	0	-0.37	7	7
GAB1	-0.017	0.1	-10000	0	-0.3	31	31
CRK	-0.01	0.1	-10000	0	-0.37	9	9
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.051	0.19	-10000	0	-0.54	47	47
JUN	0.01	0.037	-10000	0	-0.5	2	2
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.029	0.096	-10000	0	-0.26	47	47
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
cell morphogenesis	-0.004	0.13	-10000	0	-0.47	14	14
GRB2/SHC	-0.011	0.087	-10000	0	-0.36	6	6
FOS	-0.019	0.12	-10000	0	-0.47	24	24
GLMN	-0.01	0.049	-10000	0	-0.26	14	14
cell motility	-0.018	0.055	-10000	0	-0.19	33	33
HGF/MET/MUC20	-0.047	0.14	-10000	0	-0.32	69	69
cell migration	-0.011	0.085	-10000	0	-0.36	6	6
GRB2	0.012	0	-10000	0	-10000	0	0
CBL	0.012	0	-10000	0	-10000	0	0
MET/RANBP10	-0.016	0.11	-10000	0	-0.37	33	33
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.11	-10000	0	-0.49	5	5
MET/MUC20	-0.025	0.11	-10000	0	-0.38	33	33
RAP1B	0.002	0.091	-10000	0	-0.36	6	6
RAP1A	0.002	0.091	-10000	0	-0.36	6	6
HGF/MET/RANBP9	-0.039	0.14	-10000	0	-0.32	69	69
RAF1	-0.033	0.17	-10000	0	-0.57	28	28
STAT3	-0.01	0.11	-10000	0	-0.47	6	6
cell proliferation	-0.017	0.14	-10000	0	-0.4	30	30
RPS6KB1	-0.01	0.049	-10000	0	-0.24	5	5
MAPK3	-0.021	0.05	-10000	0	-10000	0	0
MAPK1	-0.021	0.05	-10000	0	-10000	0	0
RANBP9	0.012	0	-10000	0	-10000	0	0
MAPK8	0.007	0.1	-10000	0	-0.42	9	9
SRC	-0.009	0.1	-10000	0	-0.47	6	6
PI3K	-0.028	0.12	-10000	0	-0.38	23	23
MET/Glomulin	-0.027	0.11	-10000	0	-0.3	45	45
SOS1	0.012	0	-10000	0	-10000	0	0
MAP2K1	-0.024	0.16	-10000	0	-0.53	28	28
MET	-0.035	0.15	-10000	0	-0.52	33	33
MAP4K1	-0.007	0.1	-10000	0	-0.39	8	8
PTK2	0.012	0	-10000	0	-10000	0	0
MAP2K2	-0.024	0.16	-10000	0	-0.53	28	28
BAD	0.012	0.044	0.32	7	-10000	0	7
MAP2K4	0.002	0.1	-10000	0	-0.39	9	9
SHP2/GRB2/SOS1/GAB1	-0.042	0.1	-10000	0	-0.36	29	29
INPPL1	0.012	0	-10000	0	-10000	0	0
PXN	0.012	0	-10000	0	-10000	0	0
SH3KBP1	0.008	0.047	-10000	0	-0.51	3	3
HGS	-0.021	0.089	-10000	0	-0.27	29	29
PLCgamma1/PKC	0.009	0	-10000	0	-10000	0	0
HGF	-0.043	0.16	-10000	0	-0.5	40	40
RASA1	0.012	0	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
PTPRJ	0.007	0.048	-10000	0	-0.45	4	4
NCK/PLCgamma1	-0.011	0.09	-10000	0	-0.38	6	6
PDPK1	0	0.053	0.38	7	-10000	0	7
HGF/MET/SHIP	-0.047	0.15	-10000	0	-0.33	76	76

×

Cellular roles of Anthrax toxin

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.002	0.075	-10000	0	-0.54	7	7
ANTXR2	-0.01	0.11	-10000	0	-0.53	15	15
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.017	-10000	0	-0.075	19	19
monocyte activation	-0.063	0.17	-10000	0	-0.46	48	48
MAP2K2	-0.002	0.007	-10000	0	-10000	0	0
MAP2K1	-0.003	0.014	-10000	0	-10000	0	0
MAP2K7	-0.003	0.014	-10000	0	-10000	0	0
MAP2K6	-0.016	0.064	-10000	0	-0.3	17	17
CYAA	-0.005	0.076	-10000	0	-0.32	19	19
MAP2K4	-0.005	0.025	-10000	0	-0.28	2	2
IL1B	-0.011	0.075	-10000	0	-0.27	24	24
Channel	-0.002	0.081	-10000	0	-0.34	19	19
NLRP1	-0.01	0.044	-10000	0	-0.27	9	9
CALM1	0.012	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.007	0.022	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.004	0.017	0.075	19	-10000	0	19
MAPK3	-0.004	0.018	-10000	0	-0.23	1	1
MAPK1	-0.004	0.018	-10000	0	-0.23	1	1
PGR	-0.074	0.12	-10000	0	-0.29	94	94
PA/Cellular Receptors	-0.003	0.089	-10000	0	-0.37	19	19
apoptosis	-0.004	0.017	-10000	0	-0.075	19	19
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.001	0.077	-10000	0	-0.32	19	19
macrophage activation	0.011	0.023	-10000	0	-0.21	2	2
TNF	-0.069	0.19	-10000	0	-0.49	60	60
VCAM1	-0.063	0.17	-10000	0	-0.46	48	48
platelet activation	0.007	0.022	-10000	0	-10000	0	0
MAPKKK cascade	-0.005	0.027	0.14	7	-10000	0	7
IL18	-0.008	0.072	-10000	0	-0.3	18	18
negative regulation of macrophage activation	-0.004	0.017	-10000	0	-0.075	19	19
LEF	-0.004	0.017	-10000	0	-0.075	19	19
CASP1	-0.008	0.028	-10000	0	-0.14	12	12
mol:cAMP	-0.004	0.019	-10000	0	-10000	0	0
necrosis	-0.004	0.017	-10000	0	-0.075	19	19
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.077	-10000	0	-0.32	19	19
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.01	0.042	-9999	-0.34	5	5
PDGFRB	-0.001	0.078	-9999	-0.49	9	9
SPHK1	-0.024	0.077	-9999	-0.79	3	3
mol:S1P	-0.027	0.071	-9999	-0.58	4	4
S1P1/S1P/Gi	-0.051	0.16	-9999	-0.37	53	53
GNAO1	-0.017	0.11	-9999	-0.48	20	20
PDGFB-D/PDGFRB/PLCgamma1	-0.044	0.15	-9999	-0.45	17	17
PLCG1	-0.045	0.15	-9999	-0.35	50	50
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.001	0.078	-9999	-0.49	9	9
GNAI2	0.01	0.006	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GNAI1	-0.008	0.096	-9999	-0.53	12	12
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.036	-9999	-0.29	5	5
S1P1/S1P	-0.01	0.082	-9999	-0.37	8	8
negative regulation of cAMP metabolic process	-0.049	0.16	-9999	-0.36	53	53
MAPK3	-0.076	0.22	-9999	-0.53	53	53
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
KDR	0.008	0.038	-9999	-0.5	2	2
PLCB2	-0.009	0.086	-9999	-0.34	11	11
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.028	0.059	-9999	-0.37	5	5
receptor internalization	-0.032	0.066	-9999	-0.34	8	8
PTGS2	-0.15	0.36	-9999	-0.95	53	53
Rac1/GTP	-0.028	0.059	-9999	-0.37	5	5
RHOA	0.012	0	-9999	-10000	0	0
VEGFA	0.007	0.042	-9999	-0.46	3	3
negative regulation of T cell proliferation	-0.049	0.16	-9999	-0.36	53	53
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.095	-9999	-0.52	12	12
MAPK1	-0.076	0.21	-9999	-0.53	52	52
S1P1/S1P/PDGFB-D/PDGFRB	-0.012	0.096	-9999	-0.4	7	7
ABCC1	0.011	0.003	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.009	0.038	-10000	0	-0.45	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.025	0.15	0.55	12	-10000	0	12
IL27/IL27R/JAK1	-0.034	0.2	-10000	0	-0.8	11	11
TBX21	-0.047	0.21	-10000	0	-0.59	32	32
IL12B	0.001	0.054	-10000	0	-0.45	5	5
IL12A	-0.037	0.12	-10000	0	-0.35	47	47
IL6ST	-0.035	0.15	-10000	0	-0.52	33	33
IL27RA/JAK1	-0.004	0.15	-10000	0	-1.2	5	5
IL27	-0.003	0.077	-10000	0	-0.46	10	10
TYK2	0.013	0.009	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.019	0.083	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.025	0.15	0.55	12	-10000	0	12
T cell proliferation during immune response	0.025	0.15	0.55	12	-10000	0	12
MAPKKK cascade	-0.025	0.15	-10000	0	-0.55	12	12
STAT3	0.012	0	-10000	0	-10000	0	0
STAT2	0.012	0	-10000	0	-10000	0	0
STAT1	0.01	0.034	-10000	0	-0.45	2	2
IL12RB1	-0.024	0.13	-10000	0	-0.5	26	26
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.046	0.21	-10000	0	-0.58	31	31
IL27/IL27R/JAK2/TYK2	-0.025	0.15	-10000	0	-0.55	12	12
positive regulation of T cell mediated cytotoxicity	-0.025	0.15	-10000	0	-0.55	12	12
STAT1 (dimer)	-0.086	0.23	0.46	7	-0.82	18	25
JAK2	0	0.086	-10000	0	-0.54	9	9
JAK1	0.005	0.063	-10000	0	-0.54	5	5
STAT2 (dimer)	-0.018	0.14	-10000	0	-0.56	10	10
T cell proliferation	-0.047	0.16	-10000	0	-0.53	17	17
IL12/IL12R/TYK2/JAK2	-0.027	0.11	-10000	0	-0.57	3	3
IL17A	-0.02	0.082	-10000	0	-10000	0	0
mast cell activation	0.025	0.15	0.55	12	-10000	0	12
IFNG	-0.007	0.038	0.068	8	-0.099	33	41
T cell differentiation	-0.003	0.008	0.015	14	-0.021	35	49
STAT3 (dimer)	-0.018	0.14	-10000	0	-0.56	10	10
STAT5A (dimer)	-0.019	0.14	-10000	0	-0.56	10	10
STAT4 (dimer)	-0.027	0.16	-10000	0	-0.57	14	14
STAT4	-0.006	0.096	-10000	0	-0.5	13	13
T cell activation	-0.006	0.016	0.1	7	-10000	0	7
IL27R/JAK2/TYK2	-0.021	0.17	-10000	0	-0.96	7	7
GATA3	-0.041	0.23	-10000	0	-1.3	11	11
IL18	-0.009	0.084	-10000	0	-0.38	18	18
positive regulation of mast cell cytokine production	-0.018	0.14	-10000	0	-0.55	10	10
IL27/EBI3	-0.014	0.11	-10000	0	-0.37	31	31
IL27RA	-0.008	0.16	-10000	0	-1.3	5	5
IL6	-0.047	0.16	-10000	0	-0.48	44	44
STAT5A	0.011	0.024	-10000	0	-0.45	1	1
monocyte differentiation	0	0.002	-10000	0	-10000	0	0
IL2	-0.001	0.084	0.48	5	-10000	0	5
IL1B	-0.014	0.092	-10000	0	-0.37	23	23
EBI3	-0.019	0.12	-10000	0	-0.5	23	23
TNF	-0.049	0.13	-10000	0	-0.35	60	60

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.019	0.016	-10000	0	-10000	0	0
HSPA8	0.005	0.057	-10000	0	-0.54	4	4
SMAD3/SMAD4/ER alpha	-0.047	0.13	0.2	3	-0.36	47	50
AKT1	0.01	0.029	-10000	0	-0.46	1	1
GSC	-0.26	0.54	-10000	0	-1.4	71	71
NKX2-5	-0.052	0.16	-10000	0	-0.45	49	49
muscle cell differentiation	0.053	0.078	0.39	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.018	0.087	-10000	0	-0.36	3	3
SMAD4	-0.006	0.059	-10000	0	-0.59	1	1
CBFB	0.012	0	-10000	0	-10000	0	0
SAP18	0.012	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.002	0.1	-10000	0	-0.28	34	34
SMAD3/SMAD4/VDR	0.034	0.063	-10000	0	-10000	0	0
MYC	-0.005	0.095	-10000	0	-0.5	13	13
CDKN2B	-0.025	0.24	-10000	0	-1.2	12	12
AP1	0.019	0.085	-10000	0	-0.45	4	4
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.036	0.041	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.037	0.12	-10000	0	-0.43	10	10
SP3	0.014	0.004	-10000	0	-10000	0	0
CREB1	0.012	0	-10000	0	-10000	0	0
FOXH1	-0.053	0.15	-10000	0	-0.52	33	33
SMAD3/SMAD4/GR	0.007	0.081	-10000	0	-0.36	8	8
GATA3	-0.043	0.15	-10000	0	-0.5	32	32
SKI/SIN3/HDAC complex/NCoR1	0.033	0.022	-10000	0	-10000	0	0
MEF2C/TIF2	-0.059	0.15	-10000	0	-0.44	23	23
endothelial cell migration	0.021	0.23	1.3	10	-10000	0	10
MAX	0.013	0.01	-10000	0	-10000	0	0
RBBP7	0.01	0.024	-10000	0	-0.45	1	1
RBBP4	0.012	0.002	-10000	0	-10000	0	0
RUNX2	-0.051	0.16	-10000	0	-0.47	48	48
RUNX3	-0.03	0.14	-10000	0	-0.51	30	30
RUNX1	0.003	0.07	-10000	0	-0.54	6	6
CTBP1	0.012	0	-10000	0	-10000	0	0
NR3C1	-0.002	0.087	-10000	0	-0.5	11	11
VDR	0.006	0.057	-10000	0	-0.54	4	4
CDKN1A	0.006	0.26	-10000	0	-1.2	16	16
KAT2B	0.002	0.081	-10000	0	-0.54	8	8
SMAD2/SMAD2/SMAD4/FOXH1	-0.047	0.14	-10000	0	-0.38	29	29
DCP1A	0.012	0	-10000	0	-10000	0	0
SKI	0.012	0.002	-10000	0	-10000	0	0
SERPINE1	-0.022	0.23	-10000	0	-1.3	10	10
SMAD3/SMAD4/ATF2	0.019	0.055	-10000	0	-0.32	1	1
SMAD3/SMAD4/ATF3	-0.004	0.1	-10000	0	-0.34	21	21
SAP30	0.009	0.04	-10000	0	-0.54	2	2
Cbp/p300/PIAS3	0.042	0.039	-10000	0	-10000	0	0
JUN	0.017	0.083	-10000	0	-0.45	4	4
SMAD3/SMAD4/IRF7	0.007	0.085	-10000	0	-0.35	11	11
TFE3	0.014	0.018	-10000	0	-10000	0	0
COL1A2	-0.015	0.16	-10000	0	-0.65	18	18
mesenchymal cell differentiation	0.022	0.13	0.35	37	-10000	0	37
DLX1	-0.039	0.14	-10000	0	-0.45	38	38
TCF3	0.011	0.029	-10000	0	-0.54	1	1
FOS	-0.016	0.12	-10000	0	-0.47	24	24
SMAD3/SMAD4/Max	0.017	0.056	-10000	0	-0.33	1	1
Cbp/p300/SNIP1	0.03	0.014	-10000	0	-10000	0	0
ZBTB17	0.012	0.01	-10000	0	-10000	0	0
LAMC1	0.021	0.077	-10000	0	-0.46	6	6
TGIF2/HDAC complex/SMAD3/SMAD4	0.016	0.063	-10000	0	-0.32	4	4
IRF7	-0.005	0.098	-10000	0	-0.52	13	13
ESR1	-0.059	0.18	-10000	0	-0.53	48	48
HNF4A	-0.15	0.24	-10000	0	-0.5	117	117
MEF2C	-0.058	0.15	-10000	0	-0.45	21	21
SMAD2-3/SMAD4	0.004	0.07	-10000	0	-0.38	1	1
Cbp/p300/Src-1	0.035	0.023	-10000	0	-10000	0	0
IGHV3OR16-13	-0.007	0.022	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.008	0.047	-10000	0	-0.51	3	3
CREBBP	0.016	0.011	-10000	0	-10000	0	0
SKIL	0.009	0.04	-10000	0	-0.54	2	2
HDAC1	0.012	0.002	-10000	0	-10000	0	0
HDAC2	0.012	0.002	-10000	0	-10000	0	0
SNIP1	0.011	0.003	-10000	0	-10000	0	0
GCN5L2	0.005	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.027	0.065	-10000	0	-0.32	3	3
MSG1/HSC70	-0.029	0.12	-10000	0	-0.35	44	44
SMAD2	-0.005	0.043	-10000	0	-10000	0	0
SMAD3	0.009	0.044	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.027	0.043	-10000	0	-0.3	1	1
SMAD2/SMAD2/SMAD4	0	0.059	-10000	0	-0.34	9	9
NCOR1	0.012	0.002	-10000	0	-10000	0	0
NCOA2	-0.008	0.1	-10000	0	-0.52	14	14
NCOA1	0.012	0	-10000	0	-10000	0	0
MYOD/E2A	-0.014	0.088	-10000	0	-0.32	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.03	0.083	-10000	0	-0.35	2	2
IFNB1	0.007	0.073	-10000	0	-0.34	4	4
SMAD3/SMAD4/MEF2C	-0.048	0.14	-10000	0	-0.45	16	16
CITED1	-0.043	0.16	-10000	0	-0.48	41	41
SMAD2-3/SMAD4/ARC105	0.014	0.063	-10000	0	-0.34	1	1
RBL1	0.009	0.04	-10000	0	-0.54	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.021	0.1	-10000	0	-0.48	11	11
RUNX1-3/PEBPB2	-0.007	0.1	-10000	0	-0.32	34	34
SMAD7	0.035	0.083	-10000	0	-0.46	1	1
MYC/MIZ-1	0.005	0.072	-10000	0	-0.36	12	12
SMAD3/SMAD4	0.04	0.13	0.28	55	-0.41	7	62
IL10	-0.049	0.2	-10000	0	-0.5	49	49
PIASy/HDAC complex	0.008	0.011	-10000	0	-10000	0	0
PIAS3	0.014	0.005	-10000	0	-10000	0	0
CDK2	0.016	0.011	-10000	0	-10000	0	0
IL5	-0.021	0.12	-10000	0	-0.52	7	7
CDK4	0.017	0.012	-10000	0	-10000	0	0
PIAS4	0.008	0.011	-10000	0	-10000	0	0
ATF3	-0.023	0.12	-10000	0	-0.47	27	27
SMAD3/SMAD4/SP1	0.021	0.082	-10000	0	-0.34	4	4
FOXG1	-0.17	0.25	-10000	0	-0.52	129	129
FOXO3	0.018	0.026	-10000	0	-0.32	1	1
FOXO1	0.017	0.031	-10000	0	-0.32	2	2
FOXO4	0.018	0.026	-10000	0	-0.32	1	1
heart looping	-0.058	0.15	-10000	0	-0.44	21	21
CEBPB	0.012	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.014	0.11	-10000	0	-0.35	20	20
MYOD1	-0.031	0.12	-10000	0	-0.45	28	28
SMAD3/SMAD4/HNF4	-0.089	0.17	-10000	0	-0.34	88	88
SMAD3/SMAD4/GATA3	-0.024	0.14	-10000	0	-0.48	13	13
SnoN/SIN3/HDAC complex/NCoR1	0.009	0.04	-10000	0	-0.54	2	2
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.004	0.1	-10000	0	-0.39	10	10
SMAD3/SMAD4/SP1-3	0.034	0.077	-10000	0	-0.37	3	3
MED15	0.012	0	-10000	0	-10000	0	0
SP1	0.01	0.035	-10000	0	-10000	0	0
SIN3B	0.012	0.002	-10000	0	-10000	0	0
SIN3A	0.012	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.065	0.15	-10000	0	-0.43	25	25
ITGB5	0.03	0.074	-10000	0	-0.48	3	3
TGIF/SIN3/HDAC complex/CtBP	0.038	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.033	0.14	-10000	0	-0.36	49	49
AR	-0.067	0.19	-10000	0	-0.52	55	55
negative regulation of cell growth	0.025	0.057	-10000	0	-0.32	1	1
SMAD3/SMAD4/MYOD	-0.009	0.095	-10000	0	-0.33	12	12
E2F5	0.01	0.034	-10000	0	-0.45	2	2
E2F4	0.012	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.018	0.11	-10000	0	-0.41	9	9
SMAD2-3/SMAD4/FOXO1-3a-4	0.02	0.078	-10000	0	-0.32	10	10
TFDP1	0.012	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.022	0.088	-10000	0	-0.45	4	4
SMAD3/SMAD4/RUNX2	-0.022	0.13	-10000	0	-0.35	37	37
TGIF2	0.008	0.047	-10000	0	-0.51	3	3
TGIF1	0.012	0	-10000	0	-10000	0	0
ATF2	0.012	0	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0	-9999	-10000	0	0
ITGB7	0.001	0.077	-9999	-0.52	8	8
ITGA4	-0.013	0.11	-9999	-0.5	18	18
alpha4/beta7 Integrin	-0.008	0.099	-9999	-0.37	25	25
alpha4/beta1 Integrin	0	0.08	-9999	-0.35	18	18

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.005	0.084	-9999	-0.34	16	16
CRKL	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DOCK1	0.012	0	-9999	-10000	0	0
ITGA4	-0.013	0.11	-9999	-0.5	18	18
alpha4/beta7 Integrin/MAdCAM1	-0.023	0.12	-9999	-0.3	35	35
EPO	-0.016	0.1	-9999	-0.45	20	20
alpha4/beta7 Integrin	-0.008	0.099	-9999	-0.37	25	25
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0	0.08	-9999	-0.35	18	18
EPO/EPOR (dimer)	-0.02	0.11	-9999	-0.34	37	37
lamellipodium assembly	0.013	0.067	-9999	-0.3	1	1
PIK3CA	0.01	0.034	-9999	-0.45	2	2
PI3K	-0.006	0.093	-9999	-0.37	23	23
ARF6	0.012	0	-9999	-10000	0	0
JAK2	-0.012	0.11	-9999	-0.34	26	26
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
MADCAM1	-0.049	0.16	-9999	-0.49	44	44
cell adhesion	-0.024	0.12	-9999	-0.3	35	35
CRKL/CBL	0.018	0	-9999	-10000	0	0
ITGB1	0.012	0	-9999	-10000	0	0
SRC	-0.018	0.12	-9999	-0.33	33	33
ITGB7	0.001	0.077	-9999	-0.52	8	8
RAC1	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.024	0.13	-9999	-0.33	52	52
p130Cas/Crk/Dock1	0.003	0.1	-9999	-0.46	6	6
VCAM1	-0.044	0.16	-9999	-0.5	40	40
RHOA	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.063	-9999	-0.28	10	10
BCAR1	-0.011	0.11	-9999	-0.51	6	6
EPOR	-0.013	0.11	-9999	-0.48	19	19
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
Rac1/GTP	0.013	0.068	-9999	-0.31	1	1

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0.024	-9999	-0.45	1	1
EGFR	-0.004	0.092	-9999	-0.53	11	11
EGF/EGFR	-0.042	0.12	-9999	-0.29	47	47
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.013	0.11	-9999	-0.48	3	3
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.002	0.084	-9999	-0.48	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.065	0.18	-9999	-0.48	57	57
EGF/EGFR dimer/SHC	-0.032	0.13	-9999	-0.34	32	32
mol:GDP	-0.015	0.11	-9999	-0.48	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.012	0.11	-9999	-0.52	17	17
GRB2/SOS1	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.039	0.087	-9999	-0.44	3	3
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	-0.04	0.089	-9999	-0.45	3	3
FRAP1	-0.017	0.1	-9999	-0.46	3	3
EGF/EGFR dimer	-0.049	0.15	-9999	-0.36	65	65
SOS1	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.01	0.1	-9999	-0.36	28	28

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.16	0.24	-9999	-0.48	125	125
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.012	0	-9999	-10000	0	0
TCEB1	0.012	0	-9999	-10000	0	0
HIF1A/p53	0.012	0.056	-9999	-0.24	15	15
HIF1A	0.017	0.02	-9999	-10000	0	0
COPS5	0.012	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.036	0.015	-9999	-10000	0	0
FIH (dimer)	0.012	0	-9999	-10000	0	0
CDKN2A	-0.11	0.21	-9999	-0.48	91	91
ARNT/IPAS	-0.1	0.17	-9999	-0.34	125	125
HIF1AN	0.012	0	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
HIF1A/ARNT	0.023	0.02	-9999	-10000	0	0
CUL2	0.012	0	-9999	-10000	0	0
OS9	0.012	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.025	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.023	0.02	-9999	-10000	0	0
PHD1-3/OS9	0.016	0.069	-9999	-0.28	17	17
HIF1A/RACK1/Elongin B/Elongin C	0.033	0.019	-9999	-10000	0	0
VHL	0.011	0.029	-9999	-0.54	1	1
HSP90AA1	0.012	0	-9999	-10000	0	0
HIF1A/JAB1	0.023	0.02	-9999	-10000	0	0
EGLN3	-0.016	0.12	-9999	-0.53	19	19
EGLN2	0.012	0	-9999	-10000	0	0
EGLN1	0.012	0	-9999	-10000	0	0
TP53	-0.01	0.11	-9999	-0.54	15	15
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.031	0.029	-9999	-0.52	1	1
ARNT	0.012	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.012	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.034	0.1	-9999	-0.26	31	31

×

Regulation of Androgen receptor activity

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
HDAC1	0.019	0.002	-9999	-10000	0	0
SMARCC1	0.005	0.01	-9999	-10000	0	0
REL	0.01	0.038	-9999	-0.5	2	2
HDAC7	0.01	0.12	-9999	-0.47	11	11
JUN	0.009	0.037	-9999	-0.49	2	2
EP300	0.012	0	-9999	-10000	0	0
KAT2B	0	0.08	-9999	-0.54	8	8
KAT5	0.012	0.001	-9999	-10000	0	0
MAPK14	0	0.085	-9999	-0.38	17	17
FOXO1	0.011	0.024	-9999	-0.45	1	1
T-DHT/AR	0.009	0.12	-9999	-0.49	11	11
MAP2K6	-0.013	0.11	-9999	-0.53	17	17
BRM/BAF57	0.009	0.055	-9999	-0.39	7	7
MAP2K4	0.009	0.041	-9999	-0.54	2	2
SMARCA2	0.001	0.075	-9999	-0.54	7	7
PDE9A	-0.075	0.23	-9999	-1.1	14	14
NCOA2	-0.008	0.1	-9999	-0.52	14	14
CEBPA	-0.025	0.14	-9999	-0.52	26	26
EHMT2	0.012	0.003	-9999	-10000	0	0
cell proliferation	-0.018	0.16	-9999	-0.49	19	19
NR0B1	-0.025	0.11	-9999	-0.45	24	24
EGR1	-0.014	0.11	-9999	-0.48	19	19
RXRs/9cRA	-0.05	0.13	-9999	-0.27	92	92
AR/RACK1/Src	0.001	0.099	-9999	-0.42	10	10
AR/GR	-0.023	0.12	-9999	-0.37	25	25
GNB2L1	0.012	0.002	-9999	-10000	0	0
PKN1	0.012	0.001	-9999	-10000	0	0
RCHY1	0.012	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.014	0.044	-9999	-0.39	4	4
T-DHT/AR/TIF2/CARM1	-0.002	0.11	-9999	-0.42	14	14
SRC	0.011	0.079	-9999	-0.35	7	7
NR3C1	-0.003	0.088	-9999	-0.51	11	11
KLK3	-0.15	0.24	-9999	-0.64	42	42
APPBP2	0.012	0.005	-9999	-10000	0	0
TRIM24	0.011	0.004	-9999	-10000	0	0
T-DHT/AR/TIP60	0.002	0.098	-9999	-0.45	10	10
TMPRSS2	-0.13	0.34	-9999	-1.1	34	34
RXRG	-0.12	0.22	-9999	-0.5	92	92
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.011	0.029	-9999	-0.54	1	1
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.012	0.002	-9999	-10000	0	0
NR2C2	0.012	0.001	-9999	-10000	0	0
KLK2	-0.021	0.15	-9999	-0.55	7	7
AR	-0.021	0.12	-9999	-0.31	46	46
SENP1	0.012	0.001	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
MDM2	0.011	0.041	-9999	-0.54	2	2
SRY	0.001	0.006	-9999	-10000	0	0
GATA2	-0.059	0.18	-9999	-0.53	49	49
MYST2	0.012	0.001	-9999	-10000	0	0
HOXB13	-0.14	0.24	-9999	-0.53	99	99
T-DHT/AR/RACK1/Src	0.004	0.098	-9999	-0.43	10	10
positive regulation of transcription	-0.059	0.18	-9999	-0.53	49	49
DNAJA1	0.012	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.025	-9999	-0.32	2	2
NCOA1	0.015	0.005	-9999	-10000	0	0
SPDEF	-0.12	0.24	-9999	-0.54	90	90
T-DHT/AR/TIF2	0.009	0.084	-9999	-0.34	7	7
T-DHT/AR/Hsp90	0.002	0.098	-9999	-0.45	10	10
GSK3B	0.012	0.002	-9999	-10000	0	0
NR2C1	0.013	0.001	-9999	-10000	0	0
mol:T-DHT	0.008	0.082	-9999	-0.32	18	18
SIRT1	0.009	0.04	-9999	-0.54	2	2
ZMIZ2	0.013	0.006	-9999	-10000	0	0
POU2F1	0.005	0.082	-9999	-0.48	9	9
T-DHT/AR/DAX-1	-0.018	0.12	-9999	-0.5	11	11
CREBBP	0.012	0.001	-9999	-10000	0	0
SMARCE1	0.012	0.003	-9999	-10000	0	0

×

Ceramide signaling pathway

Figure S73. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S73. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.002	0.086	-10000	0	-0.35	21	21
MAP4K4	-0.009	0.11	-10000	0	-0.51	9	9
BAG4	0.011	0.029	-10000	0	-0.54	1	1
PKC zeta/ceramide	-0.002	0.048	0.14	11	-0.35	2	13
NFKBIA	0.012	0	-10000	0	-10000	0	0
BIRC3	-0.047	0.16	-10000	0	-0.51	42	42
BAX	0.003	0.022	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
AKT1	0.014	0.024	-10000	0	-0.42	1	1
BAD	-0.001	0.042	0.15	11	-10000	0	11
SMPD1	-0.006	0.067	-10000	0	-0.25	9	9
RB1	-0.012	0.068	0.15	10	-0.28	14	24
FADD/Caspase 8	-0.001	0.11	-10000	0	-0.49	10	10
MAP2K4	0.002	0.045	0.16	2	-0.28	2	4
NSMAF	0.012	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0	0.049	0.17	1	-0.27	4	5
EGF	-0.065	0.18	-10000	0	-0.48	57	57
mol:ceramide	-0.008	0.046	0.15	14	-10000	0	14
MADD	0.012	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.002	0.086	-10000	0	-0.35	21	21
ASAH1	0.012	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.012	0.067	0.15	10	-0.28	14	24
cell proliferation	-0.021	0.09	-10000	0	-0.25	33	33
BID	-0.001	0.072	-10000	0	-0.33	7	7
MAP3K1	-0.002	0.042	0.15	10	-0.15	1	11
EIF2A	0.007	0.045	0.17	1	-0.24	3	4
TRADD	0.009	0.04	-10000	0	-0.54	2	2
CRADD	0.012	0	-10000	0	-10000	0	0
MAPK3	0.01	0.046	0.17	1	-0.24	4	5
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.01	0.046	0.17	1	-0.24	4	5
Cathepsin D/ceramide	-0.002	0.045	0.14	11	-0.26	2	13
FADD	-0.01	0.11	-10000	0	-0.51	9	9
KSR1	-0.006	0.051	0.15	9	-0.26	5	14
MAPK8	0.005	0.049	0.16	2	-0.24	5	7
PRKRA	-0.001	0.042	0.15	14	-10000	0	14
PDGFA	-0.017	0.12	-10000	0	-0.5	21	21
TRAF2	0.012	0	-10000	0	-10000	0	0
IGF1	-0.067	0.19	-10000	0	-0.5	57	57
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.008	0.045	0.15	14	-10000	0	14
CTSD	0.01	0.034	-10000	0	-0.45	2	2
regulation of nitric oxide biosynthetic process	0.018	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.022	0.096	-10000	0	-0.26	33	33
PRKCD	0.009	0.04	-10000	0	-0.54	2	2
PRKCZ	0.009	0.04	-10000	0	-0.54	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.002	0.086	-10000	0	-0.35	21	21
RelA/NF kappa B1	0.018	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.012	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.016	0.11	-10000	0	-0.54	9	9
TNFR1A/BAG4/TNF-alpha	-0.027	0.12	-10000	0	-0.29	61	61
mol:Sphingosine-1-phosphate	-0.002	0.086	-10000	0	-0.35	21	21
MAP2K1	0.006	0.047	0.17	1	-0.25	4	5
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
CYCS	0.008	0.044	0.16	13	-0.2	1	14
TNFRSF1A	0.011	0.029	-10000	0	-0.54	1	1
NFKB1	0.012	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.016	0.03	-10000	0	-0.38	2	2
EIF2AK2	0.002	0.047	0.16	4	-0.25	3	7
TNF-alpha/TNFR1A/FAN	-0.026	0.12	-10000	0	-0.29	60	60
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.007	0.071	-10000	0	-0.47	2	2
MAP2K2	0.006	0.047	0.17	1	-0.25	4	5
SMPD3	-0.034	0.12	-10000	0	-0.31	48	48
TNF	-0.069	0.19	-10000	0	-0.49	60	60
PKC zeta/PAR4	0.016	0.03	-10000	0	-0.38	2	2
mol:PHOSPHOCHOLINE	0.015	0.076	0.18	52	-0.12	1	53
NF kappa B1/RelA/I kappa B alpha	0.035	0.022	-10000	0	-10000	0	0
AIFM1	0.009	0.042	0.15	14	-10000	0	14
BCL2	-0.015	0.12	-10000	0	-0.52	19	19

×

Signaling events mediated by HDAC Class III

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
EP300	0.012	0	-10000	0	-10000	0	0
HDAC4	0.01	0.034	-10000	0	-0.45	2	2
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.009	0.062	0.31	12	-10000	0	12
CDKN1A	-0.026	0.14	-10000	0	-0.7	16	16
KAT2B	0	0.08	-10000	0	-0.54	8	8
BAX	0.012	0	-10000	0	-10000	0	0
FOXO3	0.001	0.008	-10000	0	-10000	0	0
FOXO1	0.011	0.024	-10000	0	-0.45	1	1
FOXO4	0.02	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.012	0	-10000	0	-10000	0	0
TAT	0.001	0.058	-10000	0	-0.45	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.02	0.1	-10000	0	-0.34	35	35
PPARGC1A	-0.13	0.23	-10000	0	-0.49	106	106
FHL2	-0.004	0.093	-10000	0	-0.54	11	11
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.017	0.034	-10000	0	-0.33	2	2
HIST2H4A	0.009	0.062	-10000	0	-0.32	12	12
SIRT1/FOXO3a	0.003	0.031	-10000	0	-0.28	2	2
SIRT1	0.011	0.047	-10000	0	-0.48	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.023	0.036	-10000	0	-0.27	4	4
SIRT1/Histone H1b	0.009	0.06	-10000	0	-0.24	15	15
apoptosis	-0.024	0.029	0.32	1	-10000	0	1
SIRT1/PGC1A	-0.074	0.14	-10000	0	-0.29	108	108
p53/SIRT1	-0.004	0.098	0.38	11	-0.39	12	23
SIRT1/FOXO4	0.022	0.031	-10000	0	-0.26	2	2
FOXO1/FHL2/SIRT1	0.013	0.061	-10000	0	-0.29	13	13
HIST1H1E	0.004	0.062	-10000	0	-0.28	14	14
SIRT1/p300	0.017	0.034	-10000	0	-0.33	2	2
muscle cell differentiation	0.01	0.093	0.29	33	-10000	0	33
TP53	-0.008	0.11	0.19	10	-0.5	15	25
KU70/SIRT1/BAX	0.024	0.03	-10000	0	-0.32	1	1
CREBBP	0.012	0	-10000	0	-10000	0	0
MEF2D	0.012	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.008	0.057	-10000	0	-0.36	7	7
ACSS2	0.019	0.033	-10000	0	-0.33	2	2
SIRT1/PCAF/MYOD	-0.01	0.093	-10000	0	-0.29	33	33

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.013	0.11	-10000	0	-0.51	18	18
positive regulation of NF-kappaB transcription factor activity	-0.023	0.12	-10000	0	-0.38	38	38
MAP2K4	0.022	0.067	-10000	0	-0.38	3	3
IKBKB	0.012	0	-10000	0	-10000	0	0
TNFRSF10B	0.009	0.04	-10000	0	-0.54	2	2
TNFRSF10A	-0.001	0.085	-10000	0	-0.54	9	9
SMPD1	0.006	0.046	-10000	0	-0.2	14	14
IKBKG	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.019	0.12	-10000	0	-0.51	22	22
TRAIL/TRAILR2	-0.002	0.087	-10000	0	-0.36	20	20
TRAIL/TRAILR3	-0.037	0.15	-10000	0	-0.4	49	49
TRAIL/TRAILR1	-0.01	0.11	-10000	0	-0.39	25	25
TRAIL/TRAILR4	-0.023	0.12	-10000	0	-0.38	38	38
TRAIL/TRAILR1/DAP3/GTP	0.002	0.084	-10000	0	-0.32	19	19
IKK complex	-0.008	0.03	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.009	0	-10000	0	-10000	0	0
MAPK3	0	0.084	-10000	0	-0.36	19	19
MAP3K1	0.018	0.068	-10000	0	-0.41	3	3
TRAILR4 (trimer)	-0.019	0.12	-10000	0	-0.51	22	22
TRADD	0.009	0.04	-10000	0	-0.54	2	2
TRAILR1 (trimer)	-0.001	0.085	-10000	0	-0.54	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.013	0.077	-10000	0	-0.53	3	3
CFLAR	0.012	0	-10000	0	-10000	0	0
MAPK1	0	0.084	-10000	0	-0.36	19	19
TRAIL/TRAILR1/FADD/TRADD/RIP	0.014	0.086	-10000	0	-0.54	3	3
mol:ceramide	0.006	0.045	-10000	0	-0.2	14	14
FADD	0.011	0.024	-10000	0	-0.45	1	1
MAPK8	0.025	0.069	-10000	0	-0.39	4	4
TRAF2	0.012	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.041	0.16	-10000	0	-0.52	37	37
CHUK	0.012	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0	0.093	-10000	0	-0.33	26	26
DAP3	0.012	0	-10000	0	-10000	0	0
CASP10	-0.011	0.096	0.25	12	-0.37	13	25
JNK cascade	-0.023	0.12	-10000	0	-0.38	38	38
TRAIL (trimer)	-0.013	0.11	-10000	0	-0.51	18	18
TNFRSF10C	-0.041	0.16	-10000	0	-0.52	37	37
TRAIL/TRAILR1/DAP3/GTP/FADD	0.008	0.08	-10000	0	-0.3	19	19
TRAIL/TRAILR2/FADD	0.007	0.075	-10000	0	-0.3	21	21
cell death	0.006	0.045	-10000	0	-0.2	14	14
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.018	0.058	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.009	0.04	-10000	0	-0.54	2	2
CASP8	0.003	0.047	-10000	0	-0.77	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.019	0.068	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0.024	-9999	-0.45	1	1
Syndecan-3/Src/Cortactin	-0.021	0.11	-9999	-0.42	2	2
Syndecan-3/Neurocan	-0.001	0.058	-9999	-0.57	1	1
POMC	-0.064	0.18	-9999	-0.48	57	57
EGFR	-0.004	0.092	-9999	-0.53	11	11
Syndecan-3/EGFR	0.011	0.058	-9999	-0.29	11	11
AGRP	0.006	0.025	-9999	-0.45	1	1
NCSTN	0.012	0	-9999	-10000	0	0
PSENEN	0.011	0.029	-9999	-0.54	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.006	0.057	-9999	-0.54	4	4
APH1A	0.011	0.024	-9999	-0.45	1	1
NCAN	-0.015	0.099	-9999	-0.45	18	18
long-term memory	0.025	0.035	-9999	-0.54	1	1
Syndecan-3/IL8	-0.021	0.1	-9999	-0.28	29	29
PSEN1	0.012	0	-9999	-10000	0	0
Src/Cortactin	0.015	0.034	-9999	-0.36	3	3
FYN	0.011	0.024	-9999	-0.45	1	1
limb bud formation	-0.003	0.033	-9999	-0.59	1	1
MC4R	-0.022	0.11	-9999	-0.45	23	23
SRC	0.009	0.04	-9999	-0.54	2	2
PTN	-0.094	0.21	-9999	-0.5	76	76
FGFR/FGF/Syndecan-3	-0.003	0.033	-9999	-0.6	1	1
neuron projection morphogenesis	-0.039	0.11	-9999	-0.41	5	5
Syndecan-3/AgRP	0.01	0.036	-9999	-0.57	1	1
Syndecan-3/AgRP/MC4R	0.003	0.063	-9999	-0.36	3	3
Fyn/Cortactin	0.017	0.024	-9999	-0.31	2	2
SDC3	-0.003	0.033	-9999	-0.61	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.02	0.1	-9999	-0.28	29	29
IL8	-0.067	0.18	-9999	-0.5	58	58
Syndecan-3/Fyn/Cortactin	0.025	0.036	-9999	-0.55	1	1
Syndecan-3/CASK	-0.003	0.032	-9999	-0.58	1	1
alpha-MSH/MC4R	-0.061	0.15	-9999	-0.34	77	77
Gamma Secretase	0.032	0.037	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.007	0.14	-10000	0	-0.65	8	8
UGCG	-0.007	0.12	-10000	0	-0.73	9	9
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.024	0.16	-10000	0	-0.41	33	33
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.007	0.12	-10000	0	-0.72	9	9
mol:DAG	-0.004	0.048	-10000	0	-0.93	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.057	0.13	-10000	0	-0.44	33	33
FRAP1	-0.01	0.18	-10000	0	-0.51	33	33
FOXO3	0.002	0.16	-10000	0	-0.47	26	26
AKT1	-0.006	0.17	-10000	0	-0.51	26	26
GAB2	0.01	0.034	-10000	0	-0.45	2	2
SMPD1	0.01	0.031	-10000	0	-10000	0	0
SGMS1	0.009	0.047	-10000	0	-0.65	1	1
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	-0.003	0.079	-10000	0	-0.31	23	23
CALM1	0.012	0	-10000	0	-10000	0	0
cell proliferation	0	0.11	-10000	0	-0.35	21	21
EIF3A	0.012	0	-10000	0	-10000	0	0
PI3K	-0.002	0.094	-10000	0	-0.36	23	23
RPS6KB1	0.006	0.064	-10000	0	-0.73	1	1
mol:sphingomyelin	-0.004	0.048	-10000	0	-0.93	1	1
natural killer cell activation	0	0.002	-10000	0	-0.012	7	7
JAK3	0.003	0.076	-10000	0	-0.51	8	8
PIK3R1	-0.016	0.12	-10000	0	-0.52	21	21
JAK1	0.007	0.064	-10000	0	-0.54	5	5
NFKB1	0.012	0	-10000	0	-10000	0	0
MYC	-0.009	0.2	-10000	0	-0.73	19	19
MYB	-0.029	0.25	-10000	0	-1.2	16	16
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.006	0.16	-10000	0	-0.51	21	21
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.019	0.061	-10000	0	-0.66	1	1
mol:PI-3-4-5-P3	-0.005	0.15	-10000	0	-0.49	21	21
Rac1/GDP	0.005	0.072	-10000	0	-0.29	17	17
T cell proliferation	0.001	0.15	-10000	0	-0.52	17	17
SHC1	0.012	0.002	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.014	-10000	0	-0.065	16	16
PRKCZ	-0.001	0.15	-10000	0	-0.54	17	17
NF kappa B1 p50/RelA	-0.022	0.15	-10000	0	-0.5	21	21
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.016	0.15	-10000	0	-0.5	22	22
HSP90AA1	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL2RA	-0.022	0.13	-10000	0	-0.51	24	24
IL2RB	-0.021	0.13	-10000	0	-0.51	25	25
TERT	-0.083	0.2	-10000	0	-0.5	68	68
E2F1	0	0.1	-10000	0	-0.44	18	18
SOS1	0.012	0.003	-10000	0	-10000	0	0
RPS6	0.011	0.029	-10000	0	-0.54	1	1
mol:cAMP	-0.001	0.007	0.031	16	-10000	0	16
PTPN11	0.012	0.003	-10000	0	-10000	0	0
IL2RG	-0.02	0.13	-10000	0	-0.5	25	25
actin cytoskeleton organization	0.001	0.15	-10000	0	-0.52	17	17
GRB2	0.012	0.003	-10000	0	-10000	0	0
IL2	-0.012	0.09	-10000	0	-0.45	15	15
PIK3CA	0.012	0.034	-10000	0	-0.45	2	2
Rac1/GTP	0.012	0.07	-10000	0	-0.27	17	17
LCK	-0.015	0.12	-10000	0	-0.5	21	21
BCL2	-0.016	0.22	-10000	0	-0.72	25	25

×

IL2 signaling events mediated by STAT5

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
GAB2	0.01	0.034	-9999	-0.45	2	2
ELF1	-0.001	0.08	-9999	-0.34	17	17
CCNA2	0.005	0.064	-9999	-0.54	5	5
PIK3CA	0.01	0.034	-9999	-0.45	2	2
JAK3	0.002	0.076	-9999	-0.5	8	8
PIK3R1	-0.017	0.12	-9999	-0.52	21	21
JAK1	0.005	0.064	-9999	-0.54	5	5
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.003	0.14	-9999	-0.51	17	17
SHC1	0.013	0	-9999	-10000	0	0
SP1	0.003	0.066	-9999	-0.34	7	7
IL2RA	-0.017	0.18	-9999	-0.66	24	24
IL2RB	-0.022	0.13	-9999	-0.51	25	25
SOS1	0.013	0	-9999	-10000	0	0
IL2RG	-0.022	0.13	-9999	-0.5	25	25
G1/S transition of mitotic cell cycle	-0.014	0.16	-9999	-0.52	26	26
PTPN11	0.013	0	-9999	-10000	0	0
CCND2	-0.007	0.14	-9999	-0.51	23	23
LCK	-0.016	0.12	-9999	-0.5	21	21
GRB2	0.013	0	-9999	-10000	0	0
IL2	-0.013	0.09	-9999	-0.45	15	15
CDK6	-0.014	0.12	-9999	-0.51	19	19
CCND3	0.013	0.13	-9999	-0.53	9	9

×

Ras signaling in the CD4+ TCR pathway

Figure S79. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S79. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.002	0.12	-9999	-0.45	13	13
MAP3K8	0.006	0.057	-9999	-0.54	4	4
FOS	-0.001	0.12	-9999	-0.54	8	8
PRKCA	-0.012	0.11	-9999	-0.53	17	17
PTPN7	-0.007	0.099	-9999	-0.48	15	15
HRAS	0.011	0.024	-9999	-0.45	1	1
PRKCB	-0.026	0.13	-9999	-0.49	28	28
NRAS	0.005	0.064	-9999	-0.54	5	5
RAS family/GTP	0.019	0.039	-9999	-0.28	6	6
MAPK3	0	0.097	-9999	-0.6	6	6
MAP2K1	-0.01	0.13	-9999	-0.42	27	27
ELK1	0.012	0.005	-9999	-10000	0	0
BRAF	-0.015	0.12	-9999	-0.43	27	27
mol:GTP	0	0.001	-9999	-0.004	24	24
MAPK1	0	0.097	-9999	-0.6	6	6
RAF1	-0.015	0.12	-9999	-0.43	27	27
KRAS	0.012	0.001	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.002	0.068	-10000	0	-0.35	4	4
epithelial cell differentiation	-0.062	0.12	-10000	0	-0.45	15	15
ITCH	0.018	0.033	-10000	0	-0.54	1	1
WWP1	0.004	0.061	-10000	0	-10000	0	0
FYN	0.011	0.024	-10000	0	-0.45	1	1
EGFR	-0.004	0.092	-10000	0	-0.53	11	11
PRL	-0.022	0.12	-10000	0	-0.45	25	25
neuron projection morphogenesis	0.008	0.088	-10000	0	-0.38	1	1
PTPRZ1	-0.038	0.14	-10000	0	-0.45	36	36
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.002	0.094	-10000	0	-0.42	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.022	0.1	-10000	0	-0.37	9	9
ADAM17	0.017	0.043	-10000	0	-0.54	2	2
ErbB4/ErbB4	-0.003	0.077	-10000	0	-0.39	3	3
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.021	0.099	-10000	0	-0.37	9	9
NCOR1	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.015	0.1	-10000	0	-0.37	8	8
GRIN2B	-0.021	0.11	-10000	0	-0.42	8	8
ErbB4/ErbB2/betacellulin	-0.011	0.099	-10000	0	-0.37	9	9
STAT1	0.01	0.034	-10000	0	-0.45	2	2
HBEGF	0.011	0.024	-10000	0	-0.45	1	1
PRLR	-0.067	0.19	-10000	0	-0.52	55	55
E4ICDs/ETO2	-0.019	0.11	-10000	0	-0.39	13	13
axon guidance	0.001	0.074	-10000	0	-10000	0	0
NEDD4	0.009	0.075	-10000	0	-0.53	7	7
Prolactin receptor/Prolactin receptor/Prolactin	-0.063	0.16	-10000	0	-0.37	76	76
CBFA2T3	-0.027	0.13	-10000	0	-0.48	29	29
ErbB4/ErbB2/HBEGF	0.007	0.07	-10000	0	-0.34	4	4
MAPK3	0.003	0.09	-10000	0	-0.4	1	1
STAT1 (dimer)	0.001	0.069	-10000	0	-0.35	4	4
MAPK1	0.003	0.09	-10000	0	-0.4	1	1
JAK2	-0.001	0.085	-10000	0	-0.54	9	9
ErbB4/ErbB2/neuregulin 1 beta	-0.022	0.11	-10000	0	-0.36	12	12
NRG1	-0.02	0.12	-10000	0	-0.35	43	43
NRG3	-0.029	0.12	-10000	0	-0.45	29	29
NRG2	-0.048	0.16	-10000	0	-0.5	43	43
NRG4	-0.037	0.15	-10000	0	-0.51	35	35
heart development	0.001	0.074	-10000	0	-10000	0	0
neural crest cell migration	-0.022	0.11	-10000	0	-0.35	12	12
ERBB2	0.011	0.067	-10000	0	-0.34	13	13
WWOX/E4ICDs	0.002	0.068	-10000	0	-0.34	3	3
SHC1	0.012	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.025	0.11	-10000	0	-0.41	9	9
apoptosis	0.033	0.076	0.34	4	-10000	0	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.032	0.12	-10000	0	-0.45	12	12
ErbB4/ErbB2/epiregulin	-0.054	0.13	-10000	0	-0.4	8	8
ErbB4/ErbB4/betacellulin/betacellulin	-0.017	0.1	-10000	0	-0.44	7	7
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.041	0.15	-10000	0	-0.44	27	27
MDM2	0.003	0.074	-10000	0	-0.38	5	5
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.015	0.096	-10000	0	-0.33	8	8
STAT5A	0.007	0.071	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.023	0.11	-10000	0	-0.42	9	9
DLG4	0.009	0.04	-10000	0	-0.54	2	2
GRB2/SHC	0.018	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.002	0.06	-10000	0	-0.32	3	3
STAT5A (dimer)	-0.065	0.12	-10000	0	-0.5	13	13
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.007	0.069	-10000	0	-10000	0	0
LRIG1	-0.016	0.12	-10000	0	-0.54	19	19
EREG	-0.11	0.21	-10000	0	-0.47	90	90
BTC	-0.022	0.13	-10000	0	-0.54	23	23
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.001	0.075	-10000	0	-10000	0	0
ERBB4	-0.003	0.078	-10000	0	-0.4	3	3
STAT5B	0.012	0	-10000	0	-10000	0	0
YAP1	0.007	0.024	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.018	0.11	-10000	0	-0.42	10	10
glial cell differentiation	-0.002	0.06	0.32	3	-10000	0	3
WWOX	0.011	0.029	-10000	0	-0.54	1	1
cell proliferation	-0.03	0.13	-10000	0	-0.46	14	14

×

PLK2 and PLK4 events

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
PLK2	-0.003	0.086	-9999	-0.49	11	11
PLK4	0.003	0.07	-9999	-0.54	6	6
regulation of centriole replication	0.002	0.08	-9999	-0.36	17	17

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.014	0.14	-9999	-0.4	31	31
MAP4K1	-0.006	0.095	-9999	-0.48	14	14
MAP3K8	0.006	0.057	-9999	-0.54	4	4
PRKCB	-0.026	0.13	-9999	-0.49	28	28
DBNL	0.012	0	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
MAP3K1	0.008	0.1	-9999	-0.5	8	8
JUN	-0.005	0.14	-9999	-0.63	15	15
MAP3K7	0.008	0.096	-9999	-0.47	8	8
GRAP2	-0.028	0.14	-9999	-0.5	29	29
CRK	0.012	0	-9999	-10000	0	0
MAP2K4	0.012	0.099	-9999	-0.45	9	9
LAT	0.001	0.074	-9999	-0.5	8	8
LCP2	0	0.079	-9999	-0.5	9	9
MAPK8	-0.01	0.14	-9999	-0.66	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.002	0.1	-9999	-0.5	8	8
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.006	0.13	-9999	-0.65	9	9

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.17	0.38	-9999	-1	52	52
RAD9A	0.012	0	-9999	-10000	0	0
AP1	-0.008	0.092	-9999	-0.34	25	25
IFNAR2	0.01	0.029	-9999	-0.54	1	1
AKT1	-0.028	0.086	-9999	-0.26	16	16
ER alpha/Oestrogen	-0.044	0.14	-9999	-0.39	48	48
NFX1/SIN3/HDAC complex	0.031	0.026	-9999	-10000	0	0
EGF	-0.066	0.18	-9999	-0.48	57	57
SMG5	0.012	0	-9999	-10000	0	0
SMG6	0.012	0	-9999	-10000	0	0
SP3/HDAC2	0.015	0.013	-9999	-10000	0	0
TERT/c-Abl	-0.15	0.35	-9999	-0.98	49	49
SAP18	0.012	0.002	-9999	-10000	0	0
MRN complex	0.024	0.018	-9999	-0.32	1	1
WT1	-0.13	0.23	-9999	-0.5	104	104
WRN	0.012	0	-9999	-10000	0	0
SP1	0.01	0.011	-9999	-10000	0	0
SP3	0.011	0.005	-9999	-10000	0	0
TERF2IP	0.012	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.15	0.3	-9999	-0.89	46	46
Mad/Max	0.015	0.019	-9999	-0.31	1	1
TERT	-0.18	0.4	-9999	-1.1	50	50
CCND1	-0.16	0.38	-9999	-1	57	57
MAX	0.011	0.005	-9999	-10000	0	0
RBBP7	0.01	0.024	-9999	-0.45	1	1
RBBP4	0.012	0.002	-9999	-10000	0	0
TERF2	0.012	0.004	-9999	-10000	0	0
PTGES3	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0.002	-9999	-10000	0	0
Telomerase/911	0.017	0.039	-9999	-10000	0	0
CDKN1B	-0.033	0.16	-9999	-0.58	22	22
RAD1	0.012	0	-9999	-10000	0	0
XRCC5	0.012	0	-9999	-10000	0	0
XRCC6	0.012	0	-9999	-10000	0	0
SAP30	0.009	0.04	-9999	-0.54	2	2
TRF2/PARP2	0.018	0.003	-9999	-10000	0	0
UBE3A	0.011	0.005	-9999	-10000	0	0
JUN	0.008	0.037	-9999	-0.49	2	2
E6	-0.002	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.007	0.007	-9999	-10000	0	0
FOS	-0.02	0.12	-9999	-0.47	24	24
IFN-gamma/IRF1	-0.03	0.13	-9999	-0.33	53	53
PARP2	0.012	0	-9999	-10000	0	0
BLM	0.008	0.049	-9999	-0.54	3	3
Telomerase	-0.004	0.078	-9999	-0.46	6	6
IRF1	0.002	0.056	-9999	-0.45	3	3
ESR1	-0.06	0.18	-9999	-0.54	48	48
KU/TER	0.018	0	-9999	-10000	0	0
ATM/TRF2	0.018	0.019	-9999	-0.34	1	1
ubiquitin-dependent protein catabolic process	0.035	0.025	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.035	0.025	-9999	-10000	0	0
HDAC1	0.012	0.002	-9999	-10000	0	0
HDAC2	0.009	0.011	-9999	-10000	0	0
ATM	-0.001	0.022	-9999	-0.42	1	1
SMAD3	0.019	0.025	-9999	-0.31	2	2
ABL1	0.012	0	-9999	-10000	0	0
MXD1	0.01	0.024	-9999	-0.45	1	1
MRE11A	0.012	0	-9999	-10000	0	0
HUS1	0.012	0	-9999	-10000	0	0
RPS6KB1	0.011	0.029	-9999	-0.54	1	1
TERT/NF kappa B1/14-3-3	-0.14	0.35	-9999	-0.96	48	48
NR2F2	0.008	0.065	-9999	-0.54	5	5
MAPK3	-0.003	0.067	-9999	-0.32	16	16
MAPK1	-0.003	0.067	-9999	-0.32	16	16
TGFB1/TGF beta receptor Type II	0.011	0.034	-9999	-0.45	2	2
NFKB1	0.012	0	-9999	-10000	0	0
HNRNPC	0.012	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.022	-9999	-0.41	1	1
NBN	0.011	0.029	-9999	-0.54	1	1
EGFR	-0.005	0.093	-9999	-0.53	11	11
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.051	0.15	-9999	-0.36	65	65
MYC	-0.008	0.097	-9999	-0.51	13	13
IL2	-0.017	0.091	-9999	-0.46	15	15
KU	0.018	0	-9999	-10000	0	0
RAD50	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
TGFB1	0.011	0.034	-9999	-0.45	2	2
TRF2/BLM	0.015	0.034	-9999	-0.36	3	3
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.14	0.36	-9999	-1	46	46
SP1/HDAC2	0.015	0.019	-9999	-10000	0	0
PINX1	0.012	0	-9999	-10000	0	0
Telomerase/EST1A	-0.15	0.3	-9999	-0.89	46	46
Smad3/Myc	0.012	0.064	-9999	-0.29	15	15
911 complex	0.025	0	-9999	-10000	0	0
IFNG	-0.044	0.15	-9999	-0.47	36	36
Telomerase/PinX1	-0.15	0.3	-9999	-0.89	46	46
Telomerase/AKT1/mTOR/p70S6K	-0.017	0.084	-9999	-0.34	2	2
SIN3B	0.012	0.002	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
Telomerase/EST1B	-0.15	0.3	-9999	-0.89	46	46
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.035	0.015	-9999	-10000	0	0
TRF2/WRN	0.018	0.003	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.15	0.3	-9999	-0.89	46	46
E2F1	0.002	0.067	-9999	-0.48	7	7
ZNFX1	0.012	0.002	-9999	-10000	0	0
PIF1	0.001	0.077	-9999	-0.52	8	8
NCL	0.012	0	-9999	-10000	0	0
DKC1	0.012	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.012	0.001	-9999	-10000	0	0
HDAC2	0.012	0.001	-9999	-10000	0	0
GNB1/GNG2	0.004	0.073	-9999	-0.3	20	20
forebrain development	-0.058	0.2	-9999	-0.53	44	44
GNAO1	-0.014	0.11	-9999	-0.47	20	20
SMO/beta Arrestin2	0.007	0.062	-9999	-0.38	9	9
SMO	-0.002	0.085	-9999	-0.54	9	9
ARRB2	0.011	0.005	-9999	-10000	0	0
GLI3/SPOP	0.023	0.075	-9999	-0.46	1	1
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0.012	0	-9999	-10000	0	0
GNAI2	0.012	0.003	-9999	-10000	0	0
SIN3/HDAC complex	0.031	0.024	-9999	-0.28	2	2
GNAI1	-0.006	0.095	-9999	-0.52	12	12
XPO1	0.012	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.04	0.17	-9999	-0.5	24	24
SAP30	0.01	0.04	-9999	-0.54	2	2
mol:GDP	-0.002	0.085	-9999	-0.54	9	9
MIM/GLI2A	-0.017	0.11	-9999	-0.54	15	15
IFT88	0.011	0.029	-9999	-0.54	1	1
GNAI3	0.012	0.003	-9999	-10000	0	0
GLI2	0.03	0.038	-9999	-10000	0	0
GLI3	0.017	0.079	-9999	-0.38	2	2
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
SAP18	0.012	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.011	0.029	-9999	-0.54	1	1
GNG2	-0.002	0.084	-9999	-0.48	11	11
Gi family/GTP	-0.004	0.09	-9999	-0.3	18	18
SIN3B	0.012	0.001	-9999	-10000	0	0
SIN3A	0.012	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.029	0.065	-9999	-0.47	2	2
GLI2/Su(fu)	0.032	0.05	-9999	-10000	0	0
FOXA2	-0.24	0.46	-9999	-1.1	77	77
neural tube patterning	-0.058	0.2	-9999	-0.53	44	44
SPOP	0.012	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.022	0.036	-9999	-0.33	1	1
GNB1	0.012	0	-9999	-10000	0	0
CSNK1G2	0.012	0	-9999	-10000	0	0
CSNK1G3	0.012	0	-9999	-10000	0	0
MTSS1	-0.017	0.11	-9999	-0.54	15	15
embryonic limb morphogenesis	-0.058	0.2	-9999	-0.53	44	44
SUFU	0.015	0.04	-9999	-0.37	1	1
LGALS3	0.005	0.064	-9999	-0.54	5	5
catabolic process	0.039	0.076	-9999	-0.41	1	1
GLI3A/CBP	-0.026	0.12	-9999	-0.34	40	40
KIF3A	0.011	0.029	-9999	-0.54	1	1
GLI1	-0.06	0.2	-9999	-0.54	44	44
RAB23	0.011	0.029	-9999	-0.54	1	1
CSNK1A1	0.012	0	-9999	-10000	0	0
IFT172	0.012	0	-9999	-10000	0	0
RBBP7	0.011	0.024	-9999	-0.45	1	1
Su(fu)/Galectin3	0.018	0.05	-9999	-0.29	6	6
GNAZ	-0.005	0.094	-9999	-0.52	12	12
RBBP4	0.012	0.001	-9999	-10000	0	0
CSNK1G1	0.012	0	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GLI2/SPOP	0.034	0.036	-9999	-10000	0	0
STK36	0.011	0.029	-9999	-0.54	1	1
Gi family/GNB1/GNG2/GDP	0.001	0.087	-9999	-0.45	5	5
PTCH1	-0.048	0.19	-9999	-0.58	26	26
MIM/GLI1	-0.11	0.29	-9999	-0.6	85	85
CREBBP	-0.026	0.12	-9999	-0.34	40	40
Su(fu)/SIN3/HDAC complex	0.041	0.022	-9999	-10000	0	0

×

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

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
BAG4	0.011	0.029	-9999	-0.54	1	1
Caspase 8 (4 units)	0.004	0.083	-9999	-0.39	3	3
NEF	-0.012	0.048	-9999	-10000	0	0
NFKBIA	0.003	0.033	-9999	-10000	0	0
BIRC3	-0.024	0.18	-9999	-0.51	42	42
CYCS	0.004	0.09	-9999	-0.44	2	2
RIPK1	0.012	0	-9999	-10000	0	0
CD247	-0.04	0.16	-9999	-0.59	27	27
MAP2K7	0.006	0.083	-9999	-0.51	2	2
protein ubiquitination	0.021	0.078	-9999	-0.38	4	4
CRADD	0.012	0	-9999	-10000	0	0
DAXX	0.012	0	-9999	-10000	0	0
FAS	0.001	0.079	-9999	-0.53	8	8
BID	-0.001	0.094	-9999	-0.47	2	2
NF-kappa-B/RelA/I kappa B alpha	0.002	0.091	-9999	-10000	0	0
TRADD	0.009	0.04	-9999	-0.54	2	2
MAP3K5	0.004	0.064	-9999	-0.5	6	6
CFLAR	0.012	0	-9999	-10000	0	0
FADD	0.011	0.024	-9999	-0.45	1	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.002	0.092	-9999	-10000	0	0
MAPK8	0.011	0.082	-9999	-0.43	3	3
APAF1	0.012	0	-9999	-10000	0	0
TRAF1	0.01	0.037	-9999	-0.5	2	2
TRAF2	0.012	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.007	0.098	-9999	-0.28	26	26
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.008	0.095	-9999	-0.48	5	5
CHUK	0.02	0.083	-9999	-0.42	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.025	0.057	-9999	-10000	0	0
TCRz/NEF	-0.042	0.16	-9999	-0.39	54	54
TNF	-0.069	0.19	-9999	-0.49	60	60
FASLG	-0.061	0.22	-9999	-0.58	51	51
NFKB1	0.003	0.033	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.027	0.12	-9999	-0.29	61	61
CASP6	0.019	0.071	-9999	-0.5	1	1
CASP7	-0.005	0.17	-9999	-0.53	29	29
RELA	0.003	0.033	-9999	-10000	0	0
CASP2	0.012	0	-9999	-10000	0	0
CASP3	-0.004	0.17	-9999	-0.53	28	28
TNFRSF1A	0.011	0.029	-9999	-0.54	1	1
TNFR1A/BAG4	0.016	0.03	-9999	-0.38	2	2
CASP8	0.011	0.029	-9999	-0.54	1	1
CASP9	0.011	0.024	-9999	-0.45	1	1
MAP3K14	0.015	0.09	-9999	-0.47	4	4
APAF-1/Caspase 9	-0.053	0.12	-9999	-0.4	31	31
BCL2	0.004	0.1	-9999	-0.39	10	10

×

Signaling events mediated by PRL

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.014	0.11	-10000	0	-0.5	19	19
mol:Halofuginone	0.004	0.012	-10000	0	-0.22	1	1
ITGA1	-0.006	0.095	-10000	0	-0.48	14	14
CDKN1A	0.003	0.1	-10000	0	-0.43	15	15
PRL-3/alpha Tubulin	0.013	0.043	-10000	0	-0.36	5	5
mol:Ca2+	-0.087	0.16	0.32	3	-0.36	92	95
AGT	-0.12	0.22	-10000	0	-0.49	93	93
CCNA2	0.014	0.088	-10000	0	-0.6	4	4
TUBA1B	0.012	0	-10000	0	-10000	0	0
EGR1	0.001	0.081	-10000	0	-0.34	20	20
CDK2/Cyclin E1	0.003	0.11	-10000	0	-0.37	17	17
MAPK3	0.013	0.047	-10000	0	-0.35	6	6
PRL-2 /Rab GGTase beta	0.018	0	-10000	0	-10000	0	0
MAPK1	0.013	0.047	-10000	0	-0.35	6	6
PTP4A1	0.013	0.085	-10000	0	-0.68	3	3
PTP4A3	0.005	0.06	-10000	0	-0.5	5	5
PTP4A2	0.012	0	-10000	0	-10000	0	0
ITGB1	0.014	0.044	-10000	0	-0.36	5	5
SRC	0.009	0.04	-10000	0	-0.54	2	2
RAC1	0.017	0.064	-10000	0	-0.48	4	4
Rab GGTase beta/Rab GGTase alpha	0.018	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.015	0.084	-10000	0	-0.64	3	3
RABGGTA	0.012	0	-10000	0	-10000	0	0
BCAR1	0.003	0.043	0.31	5	-0.4	1	6
RHOC	0.017	0.064	-10000	0	-0.48	4	4
RHOA	0.017	0.064	-10000	0	-0.48	4	4
cell motility	0.02	0.066	-10000	0	-0.43	5	5
PRL-1/alpha Tubulin	0.018	0.08	-10000	0	-0.64	3	3
PRL-3/alpha1 Integrin	0	0.083	-10000	0	-0.36	18	18
ROCK1	0.02	0.066	-10000	0	-0.43	5	5
RABGGTB	0.012	0	-10000	0	-10000	0	0
CDK2	0.012	0	-10000	0	-10000	0	0
mitosis	0.013	0.084	-10000	0	-0.67	3	3
ATF5	0.006	0.054	-10000	0	-0.45	5	5

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.023	0.11	-9999	-0.47	2	2
CRKL	0.006	0.084	-9999	-0.36	4	4
mol:DAG	0.01	0.089	-9999	-0.44	3	3
HRAS	0.025	0.076	-9999	-0.36	2	2
MAPK8	-0.001	0.088	-9999	-0.32	13	13
RAP1A	0.006	0.084	-9999	-0.36	4	4
GAB1	0.005	0.085	-9999	-0.36	4	4
MAPK14	0.001	0.084	-9999	-0.36	5	5
EPO	-0.016	0.1	-9999	-0.45	20	20
PLCG1	0.01	0.091	-9999	-0.46	3	3
EPOR/TRPC2/IP3 Receptors	-0.013	0.11	-9999	-0.48	19	19
RAPGEF1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.018	0.11	-9999	-0.28	52	52
GAB1/SHC/GRB2/SOS1	-0.023	0.058	-9999	-0.37	1	1
EPO/EPOR (dimer)	-0.017	0.11	-9999	-0.34	37	37
IRS2	-0.017	0.12	-9999	-0.38	17	17
STAT1	0.012	0.1	-9999	-0.42	5	5
STAT5B	0.011	0.096	-9999	-0.41	5	5
cell proliferation	0.006	0.082	-9999	-0.36	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.038	0.086	-9999	-0.43	7	7
TEC	0.001	0.092	-9999	-0.43	4	4
SOCS3	-0.009	0.1	-9999	-0.52	15	15
STAT1 (dimer)	0.012	0.1	-9999	-0.41	5	5
JAK2	-0.002	0.085	-9999	-0.54	9	9
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
EPO/EPOR (dimer)/JAK2	0.012	0.093	-9999	-0.36	5	5
EPO/EPOR	-0.017	0.11	-9999	-0.34	37	37
LYN	0.009	0.049	-9999	-0.54	3	3
TEC/VAV2	0.006	0.094	-9999	-0.39	5	5
elevation of cytosolic calcium ion concentration	-0.013	0.11	-9999	-0.48	19	19
SHC1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.002	0.096	-9999	-0.34	13	13
mol:IP3	0.01	0.089	-9999	-0.44	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.025	0.14	-9999	-0.46	20	20
SH2B3	0.01	0.009	-9999	-10000	0	0
NFKB1	0.001	0.084	-9999	-0.36	5	5
EPO/EPOR (dimer)/JAK2/SOCS3	-0.027	0.068	-9999	-0.24	21	21
PTPN6	0	0.087	-9999	-0.36	5	5
TEC/VAV2/GRB2	0.011	0.092	-9999	-0.38	5	5
EPOR	-0.013	0.11	-9999	-0.48	19	19
INPP5D	-0.002	0.088	-9999	-0.53	10	10
mol:GDP	-0.024	0.059	-9999	-0.38	1	1
SOS1	0.012	0	-9999	-10000	0	0
PLCG2	0	0.076	-9999	-0.48	9	9
CRKL/CBL/C3G	0.019	0.08	-9999	-0.35	3	3
VAV2	0.003	0.088	-9999	-0.36	5	5
CBL	0.006	0.084	-9999	-0.36	4	4
SHC/Grb2/SOS1	-0.025	0.062	-9999	-0.35	3	3
STAT5A	0.011	0.096	-9999	-0.41	5	5
GRB2	0.012	0	-9999	-10000	0	0
STAT5 (dimer)	0.021	0.11	-9999	-0.46	4	4
LYN/PLCgamma2	0.007	0.066	-9999	-0.35	12	12
PTPN11	0.012	0	-9999	-10000	0	0
BTK	-0.005	0.1	-9999	-0.42	7	7
BCL2	-0.001	0.2	-9999	-0.81	17	17

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.003	0.084	0.4	5	-10000	0	5
GNAI2	0.012	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.008	0.085	-10000	0	-0.29	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.014	0.11	-10000	0	-0.47	20	20
RhoA/GTP	-0.003	0.086	-10000	0	-0.4	5	5
negative regulation of cAMP metabolic process	-0.01	0.093	-10000	0	-0.27	25	25
GNAZ	-0.005	0.094	-10000	0	-0.52	12	12
GNAI3	0.012	0	-10000	0	-10000	0	0
GNA12	0.012	0	-10000	0	-10000	0	0
S1PR5	-0.029	0.14	-10000	0	-0.49	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.01	0.094	-10000	0	-0.28	25	25
RhoA/GDP	0.009	0	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.095	-10000	0	-0.52	12	12

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.041	0.16	-10000	0	-0.52	37	37
HRAS	0.011	0.024	-10000	0	-0.45	1	1
EGFR	-0.004	0.092	-10000	0	-0.53	11	11
AKT	0.018	0.067	-10000	0	-0.33	10	10
FOXO3	0.012	0	-10000	0	-10000	0	0
AKT1	0.011	0.024	-10000	0	-0.45	1	1
FOXO1	0.011	0.024	-10000	0	-0.45	1	1
AKT3	-0.003	0.086	-10000	0	-0.47	12	12
FOXO4	0.012	0	-10000	0	-10000	0	0
MET	-0.035	0.15	-10000	0	-0.52	33	33
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
PIK3CB	0.012	0	-10000	0	-10000	0	0
NRAS	0.005	0.064	-10000	0	-0.54	5	5
PIK3CG	-0.029	0.14	-10000	0	-0.51	29	29
PIK3R3	0.002	0.073	-10000	0	-0.53	7	7
PIK3R2	0.012	0	-10000	0	-10000	0	0
NF1	0.008	0.049	-10000	0	-0.54	3	3
RAS	-0.014	0.083	0.21	2	-0.3	15	17
ERBB2	-0.002	0.082	-10000	0	-0.47	11	11
proliferation/survival/translation	-0.015	0.048	0.22	4	-10000	0	4
PI3K	-0.016	0.096	0.18	3	-0.27	32	35
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
KRAS	0.012	0	-10000	0	-10000	0	0
FOXO	0.033	0.032	-10000	0	-10000	0	0
AKT2	0.011	0.024	-10000	0	-0.45	1	1
PTEN	0.002	0.075	-10000	0	-0.54	7	7

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.014	0.11	-9999	-0.47	20	20
CDC42/GTP	0.001	0.087	-9999	-0.43	6	6
PLCG1	0.001	0.09	-9999	-0.44	6	6
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.012	0	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0	-9999	-10000	0	0
cell migration	0.001	0.085	-9999	-0.42	6	6
S1PR5	-0.029	0.14	-9999	-0.49	30	30
S1PR4	-0.016	0.12	-9999	-0.49	21	21
MAPK3	0.001	0.091	-9999	-0.44	6	6
MAPK1	0.001	0.091	-9999	-0.44	6	6
S1P/S1P5/Gi	-0.01	0.094	-9999	-0.28	25	25
GNAI1	-0.005	0.095	-9999	-0.52	12	12
CDC42/GDP	0.009	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.008	0.085	-9999	-0.29	30	30
RHOA	0.012	0.061	-9999	-0.27	9	9
S1P/S1P4/Gi	-0.005	0.096	-9999	-0.26	33	33
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.005	0.094	-9999	-0.52	12	12
S1P/S1P4/G12/G13	0.008	0.065	-9999	-0.26	21	21
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
CDC42	0.012	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.015	0.015	-10000	0	-0.26	1	1
RAS family/GTP	0.004	0.083	-10000	0	-0.56	2	2
NFATC4	0.007	0.075	-10000	0	-0.37	2	2
ERBB2IP	0.008	0.049	-10000	0	-0.53	3	3
HSP90 (dimer)	0.012	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.006	0.085	-10000	0	-0.4	2	2
JUN	0.009	0.091	-10000	0	-0.29	19	19
HRAS	0.011	0.024	-10000	0	-0.45	1	1
DOCK7	0	0.084	-10000	0	-0.37	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.014	0.1	0.22	3	-0.29	25	28
AKT1	0.009	0.017	-10000	0	-0.32	1	1
BAD	0.015	0.014	-10000	0	-0.26	1	1
MAPK10	-0.004	0.074	-10000	0	-0.27	6	6
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.006	0.092	-10000	0	-0.43	2	2
RAF1	0.009	0.088	-10000	0	-0.46	3	3
ErbB2/ErbB3/neuregulin 2	-0.028	0.11	0.23	3	-0.27	57	60
STAT3	-0.001	0.072	-10000	0	-0.97	2	2
cell migration	0.009	0.064	0.15	2	-0.23	5	7
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.034	0.22	-10000	0	-0.58	37	37
FOS	-0.012	0.15	-10000	0	-0.35	44	44
NRAS	0.005	0.064	-10000	0	-0.54	5	5
mol:Ca2+	-0.006	0.085	-10000	0	-0.4	2	2
MAPK3	-0.021	0.17	-10000	0	-0.44	36	36
MAPK1	-0.021	0.17	-10000	0	-0.44	36	36
JAK2	-0.006	0.092	-10000	0	-0.38	4	4
NF2	-0.002	0.015	-10000	0	-0.29	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.004	0.083	-10000	0	-0.27	23	23
NRG1	-0.044	0.16	-10000	0	-0.49	41	41
GRB2/SOS1	0.018	0.001	-10000	0	-10000	0	0
MAPK8	0.004	0.081	-10000	0	-0.27	11	11
MAPK9	0.014	0.048	-10000	0	-0.22	1	1
ERBB2	-0.007	0.067	0.37	3	-0.34	11	14
ERBB3	0.006	0.057	-10000	0	-0.54	4	4
SHC1	0.012	0.001	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
apoptosis	-0.001	0.016	0.25	1	-10000	0	1
STAT3 (dimer)	0.012	0.071	-10000	0	-0.94	2	2
RNF41	0.02	0.014	-10000	0	-10000	0	0
FRAP1	0.007	0.014	-10000	0	-0.27	1	1
RAC1-CDC42/GTP	-0.02	0.05	-10000	0	-0.31	1	1
ErbB2/ErbB2/HSP90 (dimer)	0.002	0.054	0.25	3	-0.28	11	14
CHRNA1	-0.046	0.22	-10000	0	-0.6	41	41
myelination	0.009	0.074	-10000	0	-0.34	2	2
PPP3CB	0	0.079	-10000	0	-0.35	2	2
KRAS	0.012	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.009	0.073	-10000	0	-0.59	1	1
NRG2	-0.048	0.16	-10000	0	-0.5	43	43
mol:GDP	-0.004	0.083	-10000	0	-0.27	23	23
SOS1	0.012	0.001	-10000	0	-10000	0	0
MAP2K2	0.008	0.094	-10000	0	-0.46	3	3
SRC	0.009	0.04	-10000	0	-0.54	2	2
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.002	0.084	-10000	0	-0.37	2	2
MAP2K1	-0.017	0.15	-10000	0	-0.48	8	8
heart morphogenesis	-0.006	0.085	-10000	0	-0.4	2	2
RAS family/GDP	0.008	0.081	-10000	0	-0.55	2	2
GRB2	0.012	0.001	-10000	0	-10000	0	0
PRKACA	-0.002	0.005	-10000	0	-10000	0	0
CHRNE	0.004	0.046	-10000	0	-0.18	19	19
HSP90AA1	0.012	0	-10000	0	-10000	0	0
activation of caspase activity	-0.009	0.017	0.32	1	-10000	0	1
nervous system development	-0.006	0.085	-10000	0	-0.4	2	2
CDC42	0.012	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.011	0.024	-10000	0	-0.45	1	1
NFATC1	0.039	0.053	-10000	0	-10000	0	0
NFATC2	0.022	0.045	-10000	0	-0.28	2	2
NFATC3	0.018	0.03	-10000	0	-0.39	2	2
YWHAE	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.068	0.14	-10000	0	-0.41	35	35
Exportin 1/Ran/NUP214	0.024	0.006	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.084	0.13	-10000	0	-0.4	36	36
BCL2/BAX	-0.002	0.086	-10000	0	-0.37	19	19
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.01	0.004	-10000	0	-10000	0	0
BAX	0.012	0	-10000	0	-10000	0	0
MAPK14	0.012	0.002	-10000	0	-10000	0	0
BAD	0.012	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.059	0.13	-10000	0	-0.39	35	35
Calcineurin A alpha-beta B1/BCL2	-0.015	0.12	-10000	0	-0.52	19	19
FKBP8	0.012	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.058	0.13	0.38	35	-10000	0	35
KPNB1	0.012	0	-10000	0	-10000	0	0
KPNA2	0.012	0	-10000	0	-10000	0	0
XPO1	0.012	0	-10000	0	-10000	0	0
SFN	-0.056	0.18	-10000	0	-0.51	49	49
MAP3K8	0.006	0.057	-10000	0	-0.54	4	4
NFAT4/CK1 alpha	0.027	0.025	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.036	0.073	-10000	0	-0.42	2	2
CABIN1	-0.069	0.14	-10000	0	-0.41	35	35
CALM1	0.012	0.002	-10000	0	-10000	0	0
RAN	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.011	0.029	-10000	0	-0.54	1	1
CAMK4	-0.028	0.14	-10000	0	-0.49	29	29
mol:Ca2+	0	0.003	-10000	0	-10000	0	0
MAPK3	0.011	0.024	-10000	0	-0.45	1	1
YWHAH	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.006	0.065	-10000	0	-0.35	12	12
YWHAB	0.011	0.024	-10000	0	-0.45	1	1
MAPK8	0.009	0.04	-10000	0	-0.54	2	2
MAPK9	0.012	0	-10000	0	-10000	0	0
YWHAG	0.012	0	-10000	0	-10000	0	0
FKBP1A	0.012	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.051	0.053	-10000	0	-0.39	1	1
PRKCH	0.008	0.049	-10000	0	-0.54	3	3
CABIN1/Cbp/p300	0.018	0.006	-10000	0	-10000	0	0
CASP3	0.012	0.002	-10000	0	-10000	0	0
PIM1	0.01	0.034	-10000	0	-0.45	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.006	0.028	-10000	0	-0.28	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.058	-10000	0	-10000	0	0
PRKCB	-0.026	0.13	-10000	0	-0.49	28	28
PRKCE	0.011	0.029	-10000	0	-0.54	1	1
JNK2/NFAT4	0.023	0.027	-10000	0	-0.35	2	2
BAD/BCL-XL	0.017	0.017	-10000	0	-0.31	1	1
PRKCD	0.009	0.04	-10000	0	-0.54	2	2
NUP214	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.041	-10000	0	-0.54	2	2
PRKCA	-0.013	0.11	-10000	0	-0.53	17	17
PRKCG	-0.14	0.23	-10000	0	-0.48	116	116
PRKCQ	-0.083	0.21	-10000	0	-0.52	66	66
FKBP38/BCL2	-0.002	0.086	-10000	0	-0.37	19	19
EP300	0.012	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.012	0	-10000	0	-10000	0	0
NFATc/JNK1	0.042	0.055	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.017	0.004	-10000	0	-10000	0	0
FKBP12/FK506	0.009	0	-10000	0	-10000	0	0
CSNK1A1	0.016	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.008	0.084	-10000	0	-0.29	29	29
NFATc/ERK1	0.044	0.051	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.084	0.13	-10000	0	-0.4	36	36
NR4A1	0.026	0.11	-10000	0	-0.4	21	21
GSK3B	0.012	0.003	-10000	0	-10000	0	0
positive T cell selection	0.018	0.03	-10000	0	-0.38	2	2
NFAT1/CK1 alpha	-0.008	0.026	-10000	0	-0.27	1	1
RCH1/ KPNB1	0.018	0	-10000	0	-10000	0	0
YWHAQ	0.012	0	-10000	0	-10000	0	0
PRKACA	0.012	0.002	-10000	0	-10000	0	0
AKAP5	-0.004	0.09	-10000	0	-0.5	12	12
MEF2D	0.012	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.012	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.043	0.051	-10000	0	-10000	0	0
CREBBP	0.012	0.002	-10000	0	-10000	0	0
BCL2	-0.015	0.12	-10000	0	-0.52	19	19

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.02	0.04	-9999	-0.32	5	5
SNTA1	0.007	0.05	-9999	-0.47	4	4
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.014	0.059	-9999	-0.32	11	11
MAPK12	-0.002	0.084	-9999	-0.29	19	19
CCND1	-0.012	0.1	-9999	-0.45	16	16
p38 gamma/SNTA1	0.003	0.085	-9999	-0.28	19	19
MAP2K3	0.012	0	-9999	-10000	0	0
PKN1	0.012	0	-9999	-10000	0	0
G2/M transition checkpoint	-0.001	0.084	-9999	-0.29	19	19
MAP2K6	0.004	0.07	-9999	-0.3	18	18
MAPT	0.004	0.072	-9999	-0.32	13	13
MAPK13	0.014	0.047	-9999	-0.38	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.014	0.018	-9999	-0.33	1	1

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.01	-10000	0	-10000	0	0
DOCK1	0.012	0	-10000	0	-10000	0	0
ITGA4	-0.013	0.11	-10000	0	-0.5	18	18
RAC1	0.012	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.008	0.099	-10000	0	-0.37	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.012	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.01	0.069	-10000	0	-0.29	18	18
alpha4/beta7 Integrin/Paxillin	0.01	0.077	-10000	0	-0.3	16	16
lamellipodium assembly	-0.017	0.078	-10000	0	-0.36	17	17
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
PI3K	-0.006	0.093	-10000	0	-0.37	23	23
ARF6	0.012	0	-10000	0	-10000	0	0
TLN1	0.012	0	-10000	0	-10000	0	0
PXN	0.019	0	-10000	0	-10000	0	0
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
ARF6/GTP	-0.01	0.046	-10000	0	-10000	0	0
cell adhesion	0.022	0.058	-10000	0	-0.26	10	10
CRKL/CBL	0.018	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.016	0.062	-10000	0	-0.28	10	10
ITGB1	0.012	0	-10000	0	-10000	0	0
ITGB7	0.001	0.077	-10000	0	-0.52	8	8
ARF6/GDP	0.002	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.006	0.11	-10000	0	-0.31	31	31
p130Cas/Crk/Dock1	0.024	0.018	-10000	0	-0.32	1	1
VCAM1	-0.044	0.16	-10000	0	-0.5	40	40
alpha4/beta1 Integrin/Paxillin/Talin	0.023	0.059	-10000	0	-0.26	10	10
alpha4/beta1 Integrin/Paxillin/GIT1	0.023	0.059	-10000	0	-0.26	10	10
BCAR1	0.011	0.029	-10000	0	-0.54	1	1
mol:GDP	-0.022	0.058	0.26	10	-10000	0	10
CBL	0.012	0	-10000	0	-10000	0	0
PRKACA	0.012	0	-10000	0	-10000	0	0
GIT1	0.012	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.023	0.059	-10000	0	-0.26	10	10
Rac1/GTP	-0.018	0.086	-10000	0	-0.4	17	17

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.004	0.056	0.24	7	-0.46	1	8
DAPP1	-0.024	0.13	-10000	0	-0.45	21	21
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.039	0.18	-10000	0	-0.57	25	25
mol:DAG	0.001	0.089	0.18	1	-0.26	18	19
HRAS	0.011	0.024	-10000	0	-0.45	1	1
RAP1A	0.012	0.004	-10000	0	-10000	0	0
ARF5/GDP	0.022	0.063	-10000	0	-0.3	7	7
PLCG2	0	0.076	-10000	0	-0.48	9	9
PLCG1	0.012	0	-10000	0	-10000	0	0
ARF5	0.012	0	-10000	0	-10000	0	0
mol:GTP	-0.004	0.057	0.22	7	-0.5	1	8
ARF1/GTP	0.027	0.06	0.23	7	-0.48	1	8
RHOA	0.012	0	-10000	0	-10000	0	0
YES1	0.011	0.029	-10000	0	-0.54	1	1
RAP1A/GTP	0.018	0.058	0.22	7	-0.49	1	8
ADAP1	-0.011	0.066	0.22	6	-0.47	1	7
ARAP3	-0.004	0.057	0.22	7	-0.49	1	8
INPPL1	0.012	0	-10000	0	-10000	0	0
PREX1	0.001	0.076	-10000	0	-0.5	8	8
ARHGEF6	0.005	0.062	-10000	0	-0.52	5	5
ARHGEF7	0.012	0	-10000	0	-10000	0	0
ARF1	0.012	0	-10000	0	-10000	0	0
NRAS	0.005	0.064	-10000	0	-0.54	5	5
FYN	0.011	0.024	-10000	0	-0.45	1	1
ARF6	0.012	0	-10000	0	-10000	0	0
FGR	-0.004	0.091	-10000	0	-0.5	12	12
mol:Ca2+	0.006	0.048	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0	0.08	-10000	0	-0.54	8	8
ZAP70	-0.045	0.16	-10000	0	-0.5	42	42
mol:IP3	0.005	0.065	-10000	0	-0.21	4	4
LYN	0.008	0.049	-10000	0	-0.54	3	3
ARF1/GDP	0.022	0.063	-10000	0	-0.3	7	7
RhoA/GDP	0.03	0.062	0.23	5	-0.44	1	6
PDK1/Src/Hsp90	0.023	0.025	-10000	0	-0.32	2	2
BLNK	-0.006	0.097	-10000	0	-0.54	12	12
actin cytoskeleton reorganization	0.034	0.076	0.23	5	-0.36	4	9
SRC	0.009	0.04	-10000	0	-0.54	2	2
PLEKHA2	0.015	0.055	-10000	0	-0.31	10	10
RAC1	0.012	0	-10000	0	-10000	0	0
PTEN	0	0.072	-10000	0	-0.51	7	7
HSP90AA1	0.012	0	-10000	0	-10000	0	0
ARF6/GTP	-0.003	0.055	0.24	7	-0.46	1	8
RhoA/GTP	0.023	0.056	0.22	7	-0.47	1	8
Src family/SYK family/BLNK-LAT	-0.037	0.16	-10000	0	-0.48	28	28
BLK	-0.071	0.18	-10000	0	-0.49	60	60
PDPK1	0.012	0	-10000	0	-10000	0	0
CYTH1	-0.004	0.055	0.22	7	-0.47	1	8
HCK	-0.012	0.11	-10000	0	-0.51	17	17
CYTH3	-0.004	0.055	0.22	7	-0.47	1	8
CYTH2	-0.004	0.054	0.22	7	-0.47	1	8
KRAS	0.013	0.004	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.025	0.071	-10000	0	-0.52	4	4
SGK1	-0.01	0.072	-10000	0	-0.56	4	4
INPP5D	-0.002	0.088	-10000	0	-0.53	10	10
mol:GDP	0.015	0.066	-10000	0	-0.32	7	7
SOS1	0.012	0	-10000	0	-10000	0	0
SYK	0.001	0.079	-10000	0	-0.53	8	8
ARF6/GDP	0.03	0.062	0.24	5	-0.44	1	6
mol:PI-3-4-5-P3	-0.003	0.062	0.28	7	-0.5	1	8
ARAP3/RAP1A/GTP	0.018	0.059	0.22	7	-0.5	1	8
VAV1	-0.009	0.1	-10000	0	-0.52	15	15
mol:PI-3-4-P2	0.009	0.064	-10000	0	-0.38	10	10
RAS family/GTP/PI3K Class I	0.018	0.053	-10000	0	-0.5	1	1
PLEKHA1	0.015	0.055	-10000	0	-0.31	10	10
Rac1/GDP	0.022	0.063	-10000	0	-0.3	7	7
LAT	0.001	0.074	-10000	0	-0.5	8	8
Rac1/GTP	0.013	0.087	-10000	0	-0.36	15	15
ITK	-0.024	0.081	0.22	6	-0.47	1	7
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.007	0.12	0.21	1	-0.37	20	21
LCK	-0.017	0.12	-10000	0	-0.5	21	21
BTK	-0.013	0.075	0.22	7	-0.48	3	10

×

p38 MAPK signaling pathway

Figure S96. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S96. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.008	0.033	-10000	0	-0.25	6	6
TRAF2/ASK1	0.012	0.04	-10000	0	-0.3	6	6
ATM	0.011	0.029	-10000	0	-0.54	1	1
MAP2K3	0.014	0.047	-10000	0	-0.37	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.012	0.065	-10000	0	-0.31	5	5
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.002	0.083	-10000	0	-0.48	11	11
TXN	0.007	0.011	-10000	0	-0.2	1	1
CALM1	0.012	0	-10000	0	-10000	0	0
GADD45A	0.008	0.047	-10000	0	-0.51	3	3
GADD45B	0.001	0.075	-10000	0	-0.47	9	9
MAP3K1	0.011	0.029	-10000	0	-0.54	1	1
MAP3K6	0.012	0	-10000	0	-10000	0	0
MAP3K7	0.012	0	-10000	0	-10000	0	0
MAP3K4	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.012	0.047	-10000	0	-0.35	6	6
TAK1/TAB family	0.001	0.012	0.18	1	-10000	0	1
RAC1/OSM/MEKK3	0.024	0	-10000	0	-10000	0	0
TRAF2	0.012	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.007	0.026	-10000	0	-0.28	2	2
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.11	0.22	-10000	0	-0.5	91	91
CCM2	0.012	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.06	0.14	-10000	0	-0.3	91	91
MAPK11	0.008	0.044	-10000	0	-0.48	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.051	0.13	-10000	0	-0.26	96	96
OSM/MEKK3	0.018	0	-10000	0	-10000	0	0
TAOK1	0.013	0.021	-10000	0	-0.26	2	2
TAOK2	0.014	0.018	-10000	0	-0.33	1	1
TAOK3	0.014	0.018	-10000	0	-0.33	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.012	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.004	0.064	-10000	0	-0.5	6	6
MAP3K10	0.008	0.044	-10000	0	-0.48	3	3
MAP3K3	0.012	0	-10000	0	-10000	0	0
TRX/ASK1	0.009	0.039	-10000	0	-0.29	6	6
GADD45/MTK1/MTK1	0.013	0.065	-10000	0	-0.29	8	8

×

Aurora B signaling

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
Condensin I complex	0.016	0.089	-9999	-0.5	8	8
STMN1	0.009	0.07	-9999	-0.39	11	11
Aurora B/RasGAP/Survivin	0.012	0.09	-9999	-0.41	14	14
Chromosomal passenger complex/Cul3 protein complex	-0.01	0.11	-9999	-0.44	10	10
BIRC5	-0.008	0.11	-9999	-0.55	14	14
DES	-0.16	0.25	-9999	-0.59	85	85
Aurora C/Aurora B/INCENP	0.015	0.063	-9999	-0.28	16	16
Aurora B/TACC1	0.011	0.051	-9999	-0.31	9	9
Aurora B/PP2A	0.016	0.048	-9999	-0.39	5	5
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.012	0.02	-9999	-0.16	5	5
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	0.006	0.089	-9999	-0.48	11	11
Cul3 protein complex	-0.017	0.12	-9999	-0.32	45	45
KIF2C	0.009	0.092	-9999	-0.57	6	6
PEBP1	0.013	0.002	-9999	-10000	0	0
KIF20A	0.009	0.04	-9999	-0.54	2	2
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.016	0.048	-9999	-0.39	5	5
SEPT1	-0.003	0.086	-9999	-0.47	12	12
SMC2	0.012	0	-9999	-10000	0	0
SMC4	0.005	0.064	-9999	-0.54	5	5
NSUN2/NPM1/Nucleolin	0.015	0.095	-9999	-0.78	5	5
PSMA3	0.012	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	0.012	0.041	-9999	-0.34	5	5
AURKB	0.009	0.066	-9999	-0.56	5	5
AURKC	-0.001	0.083	-9999	-0.5	10	10
CDCA8	0.009	0.049	-9999	-0.53	3	3
cytokinesis	-0.003	0.12	-9999	-0.61	10	10
Aurora B/Septin1	-0.009	0.12	-9999	-0.6	9	9
AURKA	0.007	0.049	-9999	-0.54	3	3
INCENP	0.012	0.029	-9999	-0.55	1	1
KLHL13	-0.054	0.18	-9999	-0.53	45	45
BUB1	0	0.08	-9999	-0.54	8	8
hSgo1/Aurora B/Survivin	0.001	0.11	-9999	-0.39	23	23
EVI5	0.013	0.001	-9999	-10000	0	0
RhoA/GTP	-0.017	0.089	-9999	-0.58	7	7
SGOL1	-0.007	0.1	-9999	-0.53	13	13
CENPA	0.007	0.11	-9999	-0.56	11	11
NCAPG	0.005	0.064	-9999	-0.54	5	5
Aurora B/HC8 Proteasome	0.016	0.048	-9999	-0.39	5	5
NCAPD2	0.012	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.016	0.048	-9999	-0.39	5	5
RHOA	0.012	0	-9999	-10000	0	0
NCAPH	0.003	0.07	-9999	-0.54	6	6
NPM1	0.006	0.069	-9999	-0.57	5	5
RASA1	0.012	0	-9999	-10000	0	0
KLHL9	0.011	0.029	-9999	-0.54	1	1
mitotic prometaphase	0	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.048	-9999	-0.39	5	5
PPP1CC	0.012	0	-9999	-10000	0	0
Centraspindlin	0.009	0.1	-9999	-0.56	9	9
RhoA/GDP	0.009	0	-9999	-10000	0	0
NSUN2	0.006	0.069	-9999	-0.57	5	5
MYLK	0.003	0.06	-9999	-0.24	20	20
KIF23	0.01	0.041	-9999	-0.55	2	2
VIM	-0.01	0.11	-9999	-0.37	29	29
RACGAP1	0.011	0.029	-9999	-0.55	1	1
mitosis	0	0	-9999	-10000	0	0
NCL	0.006	0.069	-9999	-0.57	5	5
Chromosomal passenger complex	0.012	0.1	-9999	-0.47	11	11
Chromosomal passenger complex/EVI5	0.014	0.099	-9999	-0.56	6	6
TACC1	0.007	0.05	-9999	-0.47	4	4
PPP2R5D	0.012	0	-9999	-10000	0	0
CUL3	0.012	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0	0.082	-10000	0	-0.37	17	17
ATM	0.011	0.029	-10000	0	-0.54	1	1
UBE2D3	0.012	0	-10000	0	-10000	0	0
PRKDC	0.009	0.04	-10000	0	-0.54	2	2
ATR	0.012	0	-10000	0	-10000	0	0
UBE2L3	0.012	0	-10000	0	-10000	0	0
FANCD2	0.021	0.018	-10000	0	-0.32	1	1
protein ubiquitination	0.004	0.089	-10000	0	-0.48	2	2
XRCC5	0.012	0	-10000	0	-10000	0	0
XRCC6	0.012	0	-10000	0	-10000	0	0
M/R/N Complex	0.024	0.018	-10000	0	-0.32	1	1
MRE11A	0.012	0	-10000	0	-10000	0	0
DNA-PK	0.023	0.025	-10000	0	-0.32	2	2
FA complex/FANCD2/Ubiquitin	0.035	0.038	-10000	0	-0.35	1	1
FANCF	0.003	0.07	-10000	0	-0.54	6	6
BRCA1	0.009	0.04	-10000	0	-0.54	2	2
CCNE1	-0.014	0.11	-10000	0	-0.5	19	19
CDK2/Cyclin E1	-0.001	0.082	-10000	0	-0.35	19	19
FANCG	0.012	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.002	0.087	-10000	0	-0.37	19	19
FANCE	0.012	0	-10000	0	-10000	0	0
FANCC	0.011	0.029	-10000	0	-0.54	1	1
NBN	0.011	0.029	-10000	0	-0.54	1	1
FANCA	0.012	0	-10000	0	-10000	0	0
DNA repair	0.039	0.067	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.002	0.087	-10000	0	-0.37	19	19
BARD1/DNA-PK	0.016	0.071	-10000	0	-0.3	15	15
FANCL	0.011	0.029	-10000	0	-0.54	1	1
mRNA polyadenylation	0	0.082	0.37	17	-10000	0	17
BRCA1/BARD1/CTIP/M/R/N Complex	0.02	0.058	-10000	0	-0.38	1	1
BRCA1/BACH1/BARD1/TopBP1	0.008	0.074	-10000	0	-0.32	16	16
BRCA1/BARD1/P53	0.003	0.09	-10000	0	-0.28	31	31
BARD1/CSTF1/BRCA1	0.008	0.074	-10000	0	-0.32	16	16
BRCA1/BACH1	0.009	0.04	-10000	0	-0.54	2	2
BARD1	-0.012	0.11	-10000	0	-0.52	17	17
PCNA	0.012	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.008	0.074	-10000	0	-0.32	16	16
BRCA1/BARD1/UbcH7	0.008	0.074	-10000	0	-0.32	16	16
BRCA1/BARD1/RAD51/PCNA	0.013	0.073	-10000	0	-0.28	19	19
BARD1/DNA-PK/P53	0.01	0.087	-10000	0	-0.54	1	1
BRCA1/BARD1/Ubiquitin	-0.002	0.087	-10000	0	-0.37	19	19
BRCA1/BARD1/CTIP	0.012	0.072	-10000	0	-0.28	18	18
FA complex	0.03	0.033	-10000	0	-10000	0	0
BARD1/EWS	0	0.082	-10000	0	-0.37	17	17
RBBP8	0.016	0.034	-10000	0	-0.36	3	3
TP53	-0.01	0.11	-10000	0	-0.54	15	15
TOPBP1	0.012	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.002	0.089	0.28	31	-10000	0	31
BRCA1/BARD1	0.007	0.09	-10000	0	-0.48	2	2
CSTF1	0.012	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.009	0.082	-10000	0	-0.38	17	17
CDK2	0.012	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.008	0.049	-10000	0	-0.54	3	3
RAD50	0.012	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.002	0.087	-10000	0	-0.37	19	19
EWSR1	0.012	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0.012	0	-9999	-10000	0	0
SPHK1	-0.005	0.089	-9999	-0.47	13	13
GNAI2	0.012	0	-9999	-10000	0	0
mol:S1P	0.013	0.038	-9999	-0.28	3	3
GNAO1	-0.014	0.11	-9999	-0.47	20	20
mol:Sphinganine-1-P	0.007	0.064	-9999	-0.33	13	13
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.03	0.032	-9999	-0.26	1	1
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0	-9999	-10000	0	0
S1PR3	0.005	0.06	-9999	-0.5	5	5
S1PR2	0.011	0.029	-9999	-0.54	1	1
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.008	0.032	-9999	-0.24	3	3
S1PR5	-0.029	0.14	-9999	-0.49	30	30
S1PR4	-0.016	0.12	-9999	-0.49	21	21
GNAI1	-0.005	0.095	-9999	-0.52	12	12
S1P/S1P5/G12	0.001	0.082	-9999	-0.25	30	30
S1P/S1P3/Gq	0.007	0.091	-9999	-0.47	7	7
S1P/S1P4/Gi	0	0.095	-9999	-0.3	20	20
GNAQ	0.011	0.029	-9999	-0.54	1	1
GNAZ	-0.005	0.094	-9999	-0.52	12	12
GNA14	-0.003	0.089	-9999	-0.54	10	10
GNA15	-0.005	0.093	-9999	-0.51	12	12
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
GNA11	-0.001	0.082	-9999	-0.52	9	9
ABCC1	0.012	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.007	0.11	-10000	0	-0.48	9	9
BAG4	0.011	0.029	-10000	0	-0.54	1	1
BAD	0.009	0.039	-10000	0	-0.19	1	1
NFKBIA	0.012	0	-10000	0	-10000	0	0
BIRC3	-0.047	0.16	-10000	0	-0.51	42	42
BAX	0.009	0.039	-10000	0	-0.19	1	1
EnzymeConsortium:3.1.4.12	0	0.029	-10000	0	-0.11	9	9
IKBKB	0	0.11	-10000	0	-0.45	9	9
MAP2K2	0.014	0.052	-10000	0	-0.3	3	3
MAP2K1	0.014	0.052	-10000	0	-0.28	4	4
SMPD1	0.004	0.029	-10000	0	-0.14	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.001	0.11	-10000	0	-0.46	9	9
MAP2K4	0.012	0.047	-10000	0	-0.26	4	4
protein ubiquitination	0	0.11	-10000	0	-0.46	9	9
EnzymeConsortium:2.7.1.37	0.016	0.056	-10000	0	-0.28	5	5
response to UV	0	0.001	-10000	0	-0.002	5	5
RAF1	0.01	0.054	-10000	0	-0.27	6	6
CRADD	0.012	0	-10000	0	-10000	0	0
mol:ceramide	0.003	0.041	-10000	0	-0.15	9	9
I-kappa-B-alpha/RELA/p50/ubiquitin	0.017	0	-10000	0	-10000	0	0
MADD	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.008	0.043	-10000	0	-0.23	3	3
TRADD	0.009	0.04	-10000	0	-0.54	2	2
RELA/p50	0.012	0	-10000	0	-10000	0	0
MAPK3	0.017	0.052	-10000	0	-0.27	4	4
MAPK1	0.017	0.052	-10000	0	-0.3	3	3
p50/RELA/I-kappa-B-alpha	0.018	0	-10000	0	-10000	0	0
FADD	-0.008	0.11	-10000	0	-0.48	9	9
KSR1	0.005	0.054	-10000	0	-0.27	7	7
MAPK8	0.016	0.048	-10000	0	-0.25	5	5
TRAF2	0.012	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0	0.11	-10000	0	-0.45	9	9
TNF R/SODD	0.016	0.03	-10000	0	-0.38	2	2
TNF	-0.069	0.19	-10000	0	-0.49	60	60
CYCS	0.014	0.042	0.13	8	-0.19	2	10
IKBKG	0	0.11	-10000	0	-0.45	9	9
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.014	0.12	-10000	0	-0.51	9	9
RELA	0.012	0	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
AIFM1	0.015	0.041	0.13	8	-0.19	1	9
TNF/TNF R/SODD	-0.027	0.12	-10000	0	-0.29	61	61
TNFRSF1A	0.011	0.029	-10000	0	-0.54	1	1
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.012	0.047	-10000	0	-0.7	1	1
NSMAF	-0.007	0.11	-10000	0	-0.48	9	9
response to hydrogen peroxide	0	0.001	-10000	0	-0.002	5	5
BCL2	-0.015	0.12	-10000	0	-0.52	19	19

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.021	0.041	-10000	0	-0.24	9	9
epithelial cell differentiation	0.02	0.042	-10000	0	-0.26	8	8
CYFIP2	-0.001	0.085	-10000	0	-0.54	9	9
ENAH	0.036	0.063	-10000	0	-0.34	4	4
EGFR	-0.004	0.092	-10000	0	-0.53	11	11
EPHA2	-0.003	0.088	-10000	0	-0.51	11	11
MYO6	0.022	0.058	-10000	0	-0.52	2	2
CTNNB1	0.011	0.029	-10000	0	-0.54	1	1
ABI1/Sra1/Nap1	0.017	0.053	-10000	0	-0.32	9	9
AQP5	-0.079	0.17	-10000	0	-0.46	59	59
CTNND1	0.012	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.025	0.04	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.001	0.09	-10000	0	-0.51	2	2
EGF	-0.065	0.18	-10000	0	-0.48	57	57
NCKAP1	0.012	0	-10000	0	-10000	0	0
AQP3	-0.038	0.12	-10000	0	-0.49	24	24
cortical microtubule organization	0.02	0.042	-10000	0	-0.26	8	8
GO:0000145	0.023	0.038	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.023	0.043	-10000	0	-0.27	8	8
MLLT4	0.011	0.029	-10000	0	-0.54	1	1
ARF6/GDP	-0.015	0.056	-10000	0	-0.44	2	2
ARF6	0.012	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.016	0.068	-10000	0	-0.28	14	14
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.033	0.041	-10000	0	-10000	0	0
PVRL2	0.011	0.029	-10000	0	-0.54	1	1
ZYX	0.025	0.041	-10000	0	-10000	0	0
ARF6/GTP	0.02	0.063	-10000	0	-10000	0	0
CDH1	0.002	0.075	-10000	0	-0.54	7	7
EGFR/EGFR/EGF/EGF	-0.044	0.097	-10000	0	-0.46	6	6
RhoA/GDP	-0.005	0.036	-10000	0	-10000	0	0
actin cytoskeleton organization	0.026	0.055	-10000	0	-0.49	2	2
IGF-1R heterotetramer	-0.029	0.14	-10000	0	-0.54	28	28
GIT1	0.012	0	-10000	0	-10000	0	0
IGF1R	-0.029	0.15	-10000	0	-0.54	28	28
IGF1	-0.067	0.19	-10000	0	-0.5	57	57
DIAPH1	-0.014	0.09	-10000	0	-0.58	9	9
Wnt receptor signaling pathway	-0.02	0.042	0.26	8	-10000	0	8
RHOA	0.012	0	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.056	-10000	0	-0.44	2	2
CTNNA1	0.012	0	-10000	0	-10000	0	0
VCL	0.027	0.057	-10000	0	-0.5	2	2
EFNA1	-0.001	0.082	-10000	0	-0.52	9	9
LPP	0.028	0.043	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.017	0.066	-10000	0	-0.5	2	2
SEC6/SEC8	-0.006	0.034	-10000	0	-10000	0	0
MGAT3	0.001	0.091	-10000	0	-0.52	2	2
HGF/MET	-0.049	0.11	-10000	0	-0.51	9	9
HGF	-0.043	0.16	-10000	0	-0.5	40	40
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.021	0.041	-10000	0	-0.24	9	9
actin cable formation	0.05	0.054	-10000	0	-10000	0	0
KIAA1543	0.026	0.064	-10000	0	-0.62	2	2
KIFC3	0.022	0.05	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
EXOC3	0.012	0	-10000	0	-10000	0	0
ACTN1	0.025	0.041	-10000	0	-10000	0	0
NCK1/GIT1	0.018	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.042	-10000	0	-0.26	8	8
EXOC4	0.012	0	-10000	0	-10000	0	0
STX4	0.025	0.042	-10000	0	-10000	0	0
PIP5K1C	0.025	0.041	-10000	0	-10000	0	0
LIMA1	0.011	0.029	-10000	0	-0.54	1	1
ABI1	0.012	0	-10000	0	-10000	0	0
ROCK1	0.034	0.061	-10000	0	-0.38	2	2
adherens junction assembly	0.034	0.076	-10000	0	-0.49	4	4
IGF-1R heterotetramer/IGF1	-0.057	0.12	-10000	0	-0.55	10	10
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0.03	-10000	0	-0.38	2	2
MET	-0.035	0.15	-10000	0	-0.52	33	33
PLEKHA7	0.024	0.05	-10000	0	-0.52	1	1
mol:GTP	0.015	0.067	-10000	0	-0.28	14	14
establishment of epithelial cell apical/basal polarity	0.043	0.042	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.021	0.041	-10000	0	-0.24	9	9
regulation of cell-cell adhesion	0.026	0.055	-10000	0	-0.49	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.021	0.041	-10000	0	-0.24	9	9

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.002	0.087	-9999	-0.25	8	8
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.026	0.085	-9999	-0.37	4	4
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.008	0.068	-9999	-0.32	14	14
antigen processing and presentation of peptide antigen via MHC class I	-0.036	0.072	-9999	-0.36	8	8
CaM/Ca2+	0.003	0.08	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.006	0.086	-9999	-0.32	2	2
AKT1	0	0.11	-9999	-0.41	12	12
MAP2K1	0.012	0.079	-9999	-10000	0	0
MAP3K11	0.006	0.082	-9999	-10000	0	0
IFNGR1	0.01	0.009	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.047	0.14	-9999	-0.46	16	16
Rap1/GTP	-0.019	0.05	-9999	-10000	0	0
CRKL/C3G	0.018	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.002	0.091	-9999	-10000	0	0
CEBPB	0.034	0.091	-9999	-0.38	5	5
STAT3	0.012	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.005	0.14	-9999	-0.98	5	5
STAT1	0.005	0.085	-9999	-0.32	2	2
CALM1	0.012	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.038	0.14	-9999	-0.48	36	36
PIK3CA	0.01	0.034	-9999	-0.45	2	2
STAT1 (dimer)/PIAS1	0.012	0.082	-9999	-0.36	1	1
CEBPB/PTGES2/Cbp/p300	-0.017	0.048	-9999	-0.42	1	1
mol:Ca2+	0	0.085	-9999	-0.24	9	9
MAPK3	0.022	0.077	-9999	-10000	0	0
STAT1 (dimer)	-0.048	0.1	-9999	-0.52	8	8
MAPK1	0.022	0.077	-9999	-10000	0	0
JAK2	-0.002	0.085	-9999	-0.54	9	9
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
JAK1	0.003	0.064	-9999	-0.54	5	5
CAMK2D	0	0.08	-9999	-0.54	8	8
DAPK1	0.033	0.096	-9999	-0.61	5	5
SMAD7	0.013	0.055	-9999	-0.2	3	3
CBL/CRKL/C3G	0.017	0.076	-9999	-10000	0	0
PI3K	-0.04	0.098	-9999	-0.44	11	11
IFNG	-0.038	0.14	-9999	-0.48	36	36
apoptosis	0.021	0.076	-9999	-0.44	5	5
CAMK2G	0.012	0	-9999	-10000	0	0
STAT3 (dimer)	0.012	0	-9999	-10000	0	0
CAMK2A	-0.006	0.085	-9999	-0.45	13	13
CAMK2B	-0.11	0.22	-9999	-0.5	91	91
FRAP1	0.001	0.1	-9999	-0.38	12	12
PRKCD	0	0.11	-9999	-0.41	11	11
RAP1B	0.012	0	-9999	-10000	0	0
negative regulation of cell growth	-0.036	0.072	-9999	-0.36	8	8
PTPN2	0.012	0	-9999	-10000	0	0
EP300	0.013	0.001	-9999	-10000	0	0
IRF1	0.029	0.086	-9999	-0.47	3	3
STAT1 (dimer)/PIASy	0.01	0.083	-9999	-0.36	1	1
SOCS1	-0.012	0.14	-9999	-1.3	4	4
mol:GDP	0.014	0.073	-9999	-10000	0	0
CASP1	0.006	0.077	-9999	-0.28	16	16
PTGES2	0.012	0	-9999	-10000	0	0
IRF9	0.035	0.042	-9999	-0.31	2	2
mol:PI-3-4-5-P3	-0.039	0.095	-9999	-0.43	11	11
RAP1/GDP	-0.019	0.05	-9999	-10000	0	0
CBL	0.005	0.081	-9999	-10000	0	0
MAP3K1	0.005	0.083	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
PIAS4	0.012	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.036	0.072	-9999	-0.36	8	8
PTPN11	-0.001	0.085	-9999	-0.24	7	7
CREBBP	0.013	0.001	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.012	0.11	-10000	0	-1.2	3	3
oxygen homeostasis	0.003	0.015	-10000	0	-10000	0	0
TCEB2	0.012	0	-10000	0	-10000	0	0
TCEB1	0.012	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.021	0.064	-10000	0	-0.36	5	5
EPO	0.035	0.22	-10000	0	-0.68	6	6
FIH (dimer)	0.016	0.014	-10000	0	-10000	0	0
APEX1	0.015	0.016	-10000	0	-10000	0	0
SERPINE1	0.026	0.25	-10000	0	-0.7	18	18
FLT1	-0.008	0.091	-10000	0	-0.9	3	3
ADORA2A	0.034	0.22	-10000	0	-0.64	11	11
germ cell development	0.005	0.28	-10000	0	-0.72	28	28
SLC11A2	0.04	0.22	-10000	0	-0.64	11	11
BHLHE40	0.04	0.23	-10000	0	-0.66	11	11
HIF1AN	0.016	0.014	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.038	0.15	-10000	0	-0.46	4	4
ETS1	0.024	0.03	-10000	0	-0.54	1	1
CITED2	-0.017	0.12	-10000	0	-1.1	4	4
KDR	-0.007	0.089	-10000	0	-0.9	3	3
PGK1	0.039	0.23	-10000	0	-0.69	11	11
SIRT1	0.009	0.04	-10000	0	-0.54	2	2
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.046	0.26	-10000	0	-0.73	13	13
EPAS1	0.031	0.11	-10000	0	-0.35	9	9
SP1	0.019	0.002	-10000	0	-10000	0	0
ABCG2	0.02	0.26	-10000	0	-0.7	17	17
EFNA1	0.034	0.24	-10000	0	-0.73	12	12
FXN	0.037	0.22	-10000	0	-0.63	11	11
POU5F1	0.003	0.29	-10000	0	-0.76	28	28
neuron apoptosis	-0.046	0.25	0.71	13	-10000	0	13
EP300	0.012	0	-10000	0	-10000	0	0
EGLN3	-0.012	0.12	-10000	0	-0.53	19	19
EGLN2	0.016	0.014	-10000	0	-10000	0	0
EGLN1	0.016	0.014	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.024	0.018	-10000	0	-0.32	1	1
VHL	0.011	0.029	-10000	0	-0.54	1	1
ARNT	0.015	0.016	-10000	0	-10000	0	0
SLC2A1	0.034	0.22	-10000	0	-0.65	12	12
TWIST1	-0.007	0.28	-10000	0	-0.68	26	26
ELK1	0.019	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.045	0.14	-10000	0	-0.46	4	4
VEGFA	0.039	0.22	-10000	0	-0.64	11	11
CREBBP	0.012	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.017	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.012	0.11	-9999	-0.52	17	17
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.009	0.04	-9999	-0.54	2	2
RAC1-CDC42/GTP/PAK family	0.015	0.029	-9999	-0.22	1	1
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	0.029	-9999	-0.54	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.012	0	-9999	-10000	0	0
FYN	0.011	0.024	-9999	-0.45	1	1
MAP3K12	0.009	0.04	-9999	-0.54	2	2
FGR	-0.004	0.091	-9999	-0.5	12	12
p38 alpha/TAB1	-0.026	0.055	-9999	-0.26	9	9
PRKG1	-0.033	0.15	-9999	-0.51	32	32
DUSP8	0.002	0.075	-9999	-0.54	7	7
PGK/cGMP/p38 alpha	-0.041	0.079	-9999	-0.36	8	8
apoptosis	-0.026	0.053	-9999	-0.25	9	9
RAL/GTP	0.017	0	-9999	-10000	0	0
LYN	0.008	0.049	-9999	-0.54	3	3
DUSP1	-0.001	0.079	-9999	-0.45	11	11
PAK1	0.012	0	-9999	-10000	0	0
SRC	0.009	0.04	-9999	-0.54	2	2
RAC1/OSM/MEKK3/MKK3	0.032	0	-9999	-10000	0	0
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	0.012	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	0.012	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.017	0	-9999	-10000	0	0
MAPK11	-0.002	0.097	-9999	-0.32	12	12
BLK	-0.071	0.18	-9999	-0.49	60	60
HCK	-0.012	0.11	-9999	-0.51	17	17
MAP2K3	0.012	0	-9999	-10000	0	0
DUSP16	0.012	0	-9999	-10000	0	0
DUSP10	0.006	0.057	-9999	-0.54	4	4
TRAF6/MEKK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.007	0.078	-9999	-0.28	9	9
positive regulation of innate immune response	0.002	0.11	-9999	-0.35	12	12
LCK	-0.017	0.12	-9999	-0.5	21	21
p38alpha-beta/MKP7	0.008	0.1	-9999	-0.39	5	5
p38alpha-beta/MKP5	0.006	0.11	-9999	-0.39	10	10
PGK/cGMP	-0.024	0.11	-9999	-0.37	32	32
PAK2	0.011	0.024	-9999	-0.45	1	1
p38alpha-beta/MKP1	0.002	0.11	-9999	-0.39	7	7
CDC42	0.012	0	-9999	-10000	0	0
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
PAK3	-0.015	0.1	-9999	-0.45	19	19

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.02	0.064	-9999	-10000	0	0
TC10/GTP	-0.009	0.042	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.012	0.066	-9999	-0.3	15	15
HRAS	0.011	0.024	-9999	-0.45	1	1
APS homodimer	0.005	0.063	-9999	-0.54	5	5
GRB14	-0.11	0.22	-9999	-0.5	85	85
FOXO3	-0.002	0.074	-9999	-0.63	4	4
AKT1	-0.038	0.13	-9999	-0.44	13	13
INSR	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insulin	0.032	0.011	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0.08	-9999	-0.54	8	8
SORBS1	-0.003	0.083	-9999	-0.46	12	12
CRK	0.012	0	-9999	-10000	0	0
PTPN1	0.028	0.01	-9999	-10000	0	0
CAV1	0.007	0.067	-9999	-0.27	16	16
CBL/APS/CAP/Crk-II/C3G	0.025	0.055	-9999	-0.26	6	6
Insulin Receptor/Insulin/IRS1/NCK2	0.012	0.068	-9999	-0.3	16	16
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.026	0.08	-9999	-0.52	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.024	0.046	-9999	-10000	0	0
RPS6KB1	-0.03	0.12	-9999	-0.4	14	14
PARD6A	0.005	0.064	-9999	-0.54	5	5
CBL	0.012	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.002	0.013	-9999	-10000	0	0
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.061	0.1	-9999	-0.4	14	14
HRAS/GTP	-0.016	0.057	-9999	-0.41	1	1
Insulin Receptor	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.019	0.062	-9999	-0.27	11	11
PRKCI	-0.02	0.05	-9999	-0.55	2	2
Insulin Receptor/Insulin/GRB14/PDK1	-0.073	0.12	-9999	-0.47	13	13
SHC1	0.012	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.025	0.007	-9999	-10000	0	0
PI3K	-0.002	0.09	-9999	-0.53	2	2
NCK2	0.011	0.029	-9999	-0.54	1	1
RHOQ	0.012	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.008	0.017	-9999	-0.32	1	1
AKT2	-0.038	0.13	-9999	-0.44	13	13
PRKCZ	-0.021	0.061	-9999	-0.62	3	3
SH2B2	0.005	0.064	-9999	-0.54	5	5
SHC/SHIP	0.01	0.072	-9999	-0.26	20	20
F2RL2	-0.056	0.18	-9999	-0.51	49	49
TRIP10	0.011	0.029	-9999	-0.54	1	1
Insulin Receptor/Insulin/Shc	0.018	0.012	-9999	-0.21	1	1
TC10/GTP/CIP4/Exocyst	0.016	0.018	-9999	-0.33	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.032	0.011	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.019	0.058	-9999	-0.28	6	6
TC10/GDP	0.009	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.019	0.049	-9999	-0.3	8	8
INPP5D	0.002	0.076	-9999	-0.28	24	24
SOS1	0.012	0	-9999	-10000	0	0
SGK1	-0.017	0.094	-9999	-0.89	4	4
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	-0.011	0.11	-9999	-0.53	16	16
p62DOK/RasGAP	0.025	0.008	-9999	-10000	0	0
INS	0.002	0.023	-9999	-0.45	1	1
mol:PI-3-4-P2	0.002	0.075	-9999	-0.27	24	24
GRB2	0.012	0	-9999	-10000	0	0
EIF4EBP1	-0.031	0.13	-9999	-0.41	14	14
PTPRA	0.014	0.001	-9999	-10000	0	0
PIK3CA	0.01	0.034	-9999	-0.45	2	2
TC10/GTP/CIP4	0.016	0.018	-9999	-0.33	1	1
PDPK1	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.018	0.053	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.004	0.065	-9999	-0.3	16	16
Insulin Receptor/Insulin/IRS3	0.012	0.017	-9999	-0.31	1	1
Par3/Par6	-0.012	0.1	-9999	-0.28	36	36

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0.078	-9999	-0.49	9	9
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	0.003	0.082	-9999	-0.27	24	24
GNAO1	-0.013	0.11	-9999	-0.47	20	20
S1P/S1P3/G12/G13	0.021	0.035	-9999	-0.27	5	5
AKT1	0.011	0.071	-9999	-0.52	4	4
AKT3	0.011	0.13	-9999	-0.88	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0	0.078	-9999	-0.49	9	9
GNAI2	0.013	0.004	-9999	-10000	0	0
GNAI3	0.013	0.003	-9999	-10000	0	0
GNAI1	-0.004	0.095	-9999	-0.52	12	12
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.006	0.06	-9999	-0.51	5	5
S1PR2	0.011	0.029	-9999	-0.54	1	1
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.007	0.088	-9999	-0.3	16	16
MAPK3	0.012	0.084	-9999	-0.43	5	5
MAPK1	0.012	0.084	-9999	-0.43	5	5
JAK2	0.011	0.089	-9999	-0.39	8	8
CXCR4	0.011	0.087	-9999	-0.36	8	8
FLT1	0.01	0.045	-9999	-0.49	3	3
RhoA/GDP	0.009	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.011	0.086	-9999	-0.38	7	7
S1P/S1P3/Gi	0.007	0.089	-9999	-0.3	16	16
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	0.012	0.081	-9999	-0.42	5	5
VEGFA	0.01	0.042	-9999	-0.45	3	3
S1P/S1P2/Gi	0.008	0.079	-9999	-0.29	11	11
VEGFR1 homodimer/VEGFA homodimer	0.018	0.046	-9999	-0.33	6	6
RHOA	0.012	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.003	0.09	-9999	-0.3	25	25
GNAQ	0.011	0.029	-9999	-0.54	1	1
GNAZ	-0.004	0.094	-9999	-0.52	12	12
G12/G13	0.018	0	-9999	-10000	0	0
GNA14	-0.003	0.089	-9999	-0.54	10	10
GNA15	-0.005	0.093	-9999	-0.51	12	12
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
GNA11	-0.001	0.082	-9999	-0.52	9	9
Rac1/GTP	0.012	0.081	-9999	-0.39	6	6

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.002	0.072	-10000	0	-0.25	27	27
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.006	0.047	-10000	0	-0.32	8	8
GNB1/GNG2	0.008	0.052	-10000	0	-0.29	11	11
GNB1	0.012	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.005	0.057	-10000	0	-0.26	17	17
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.003	0.015	0.071	17	-10000	0	17
GNAL	-0.01	0.1	-10000	0	-0.48	17	17
GNG2	-0.002	0.084	-10000	0	-0.48	11	11
CRH	-0.008	0.066	-10000	0	-0.45	8	8
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.025	-10000	0	-0.34	2	2
MAPK11	0.005	0.023	-10000	0	-0.24	3	3

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.011	0.072	-9999	-0.4	6	6
PDGFB-D/PDGFRB/SLAP	0.002	0.076	-9999	-0.34	17	17
PDGFB-D/PDGFRB/APS/CBL	0.013	0.061	-9999	-0.3	14	14
AKT1	0.019	0.085	-9999	-0.47	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.011	0.075	-9999	-0.42	6	6
PIK3CA	0.01	0.034	-9999	-0.45	2	2
FGR	-0.017	0.085	-9999	-0.46	11	11
mol:Ca2+	0.012	0.066	-9999	-0.52	4	4
MYC	0.006	0.14	-9999	-0.73	11	11
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	0.025	0.041	-9999	-0.25	2	2
LRP1/PDGFRB/PDGFB	0.012	0.064	-9999	-0.35	6	6
GRB10	0	0.08	-9999	-0.54	8	8
PTPN11	0.012	0	-9999	-10000	0	0
GO:0007205	0.011	0.067	-9999	-0.53	4	4
PTEN	0.002	0.075	-9999	-0.54	7	7
GRB2	0.012	0	-9999	-10000	0	0
GRB7	-0.014	0.11	-9999	-0.47	20	20
PDGFB-D/PDGFRB/SHP2	0.01	0.056	-9999	-0.34	9	9
PDGFB-D/PDGFRB/GRB10	0.001	0.08	-9999	-0.36	17	17
cell cycle arrest	0.002	0.076	-9999	-0.34	17	17
HRAS	0.011	0.024	-9999	-0.45	1	1
HIF1A	0.024	0.077	-9999	-0.41	3	3
GAB1	0.007	0.076	-9999	-0.46	5	5
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.01	0.072	-9999	-0.42	5	5
PDGFB-D/PDGFRB	0.019	0.049	-9999	-0.29	9	9
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.01	0.056	-9999	-0.34	9	9
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.018	0.066	-9999	-0.38	6	6
positive regulation of MAPKKK cascade	0.01	0.056	-9999	-0.34	9	9
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
mol:IP3	0.012	0.068	-9999	-0.53	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.009	0.098	-9999	-0.34	28	28
SHB	0.011	0.029	-9999	-0.54	1	1
BLK	-0.056	0.15	-9999	-0.55	28	28
PTPN2	0.012	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.01	0.056	-9999	-0.34	9	9
BCAR1	0.011	0.029	-9999	-0.54	1	1
VAV2	0.006	0.089	-9999	-0.45	7	7
CBL	0.012	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.006	0.069	-9999	-0.36	12	12
LCK	-0.026	0.1	-9999	-0.47	17	17
PDGFRB	0	0.078	-9999	-0.49	9	9
ACP1	0.012	0	-9999	-10000	0	0
HCK	-0.022	0.1	-9999	-0.49	15	15
ABL1	0.005	0.071	-9999	-0.42	5	5
PDGFB-D/PDGFRB/CBL	0.005	0.082	-9999	-0.53	5	5
PTPN1	0.012	0.002	-9999	-10000	0	0
SNX15	0.012	0	-9999	-10000	0	0
STAT3	0.012	0	-9999	-10000	0	0
STAT1	0.01	0.034	-9999	-0.45	2	2
cell proliferation	0.009	0.13	-9999	-0.64	11	11
SLA	0.002	0.072	-9999	-0.48	8	8
actin cytoskeleton reorganization	0.034	0.046	-9999	-10000	0	0
SRC	-0.008	0.059	-9999	-0.41	6	6
PI3K	-0.026	0.078	-9999	-0.53	3	3
PDGFB-D/PDGFRB/GRB7/SHC	0.002	0.083	-9999	-0.28	28	28
SH2B2	0.005	0.064	-9999	-0.54	5	5
PLCgamma1/SPHK1	0.011	0.077	-9999	-0.44	6	6
LYN	-0.009	0.063	-9999	-0.45	5	5
LRP1	0.005	0.06	-9999	-0.47	6	6
SOS1	0.012	0	-9999	-10000	0	0
STAT5B	0.012	0	-9999	-10000	0	0
STAT5A	0.011	0.024	-9999	-0.45	1	1
NCK1-2/p130 Cas	0.03	0.045	-9999	-10000	0	0
SPHK1	-0.004	0.089	-9999	-0.47	13	13
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.012	0.068	-9999	-0.53	4	4
PLCG1	0.011	0.069	-9999	-0.55	4	4
NHERF/PDGFRB	0.011	0.07	-9999	-0.3	16	16
YES1	-0.006	0.049	-9999	-0.37	5	5
cell migration	0.01	0.069	-9999	-0.3	16	16
SHC/Grb2/SOS1	0.031	0.04	-9999	-10000	0	0
SLC9A3R2	0.008	0.047	-9999	-0.51	3	3
SLC9A3R1	0.005	0.06	-9999	-0.5	5	5
NHERF1-2/PDGFRB/PTEN	0.013	0.081	-9999	-0.32	14	14
FYN	-0.005	0.042	-9999	-0.34	4	4
DOK1	0.021	0.043	-9999	-0.29	4	4
HRAS/GTP	0.008	0.017	-9999	-0.32	1	1
PDGFB	0.011	0.024	-9999	-0.45	1	1
RAC1	0.01	0.11	-9999	-0.46	13	13
PRKCD	0.019	0.049	-9999	-0.29	6	6
FER	0.019	0.051	-9999	-0.29	6	6
MAPKKK cascade	-0.005	0.033	-9999	-10000	0	0
RASA1	0.021	0.043	-9999	-0.29	4	4
NCK1	0.012	0	-9999	-10000	0	0
NCK2	0.011	0.029	-9999	-0.54	1	1
p62DOK/Csk	0.027	0.04	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.008	0.059	-9999	-0.35	10	10
chemotaxis	0.005	0.069	-9999	-0.41	5	5
STAT1-3-5/STAT1-3-5	-0.005	0.035	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0.056	-9999	-0.35	9	9
PTPRJ	0.007	0.048	-9999	-0.45	4	4

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.023	0.049	-9999	-0.28	4	4
HDAC3	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.014	-9999	-10000	0	0
GATA1/HDAC4	0.008	0.045	-9999	-0.31	7	7
GATA1/HDAC5	0.01	0.038	-9999	-0.31	5	5
GATA2/HDAC5	-0.034	0.13	-9999	-0.38	49	49
HDAC5/BCL6/BCoR	0.024	0.018	-9999	-0.32	1	1
HDAC9	-0.016	0.12	-9999	-0.53	19	19
Glucocorticoid receptor/Hsp90/HDAC6	0.014	0.059	-9999	-0.3	13	13
HDAC4/ANKRA2	0.017	0.024	-9999	-0.31	2	2
HDAC5/YWHAB	0.017	0.017	-9999	-0.31	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.012	-9999	-0.21	1	1
GATA2	-0.059	0.18	-9999	-0.53	49	49
HDAC4/RFXANK	0.016	0.03	-9999	-0.31	3	3
BCOR	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0.029	-9999	-0.54	1	1
HDAC5	0.012	0	-9999	-10000	0	0
GNB1/GNG2	0.008	0.061	-9999	-0.34	11	11
Histones	0.019	0.062	-9999	-0.34	3	3
ADRBK1	0.011	0.024	-9999	-0.45	1	1
HDAC4	0.01	0.034	-9999	-0.45	2	2
XPO1	0.012	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.018	0	-9999	-10000	0	0
HDAC4/Ubc9	0.017	0.024	-9999	-0.31	2	2
HDAC7	0.011	0.024	-9999	-0.45	1	1
HDAC5/14-3-3 E	0.018	0	-9999	-10000	0	0
TUBA1B	0.012	0	-9999	-10000	0	0
HDAC6	0.01	0.037	-9999	-0.5	2	2
HDAC5/RFXANK	0.017	0.017	-9999	-0.31	1	1
CAMK4	-0.028	0.14	-9999	-0.49	29	29
Tubulin/HDAC6	0.018	0.048	-9999	-0.3	8	8
SUMO1	0.011	0.029	-9999	-0.54	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.011	0.024	-9999	-0.45	1	1
GATA1	0	0.053	-9999	-0.45	5	5
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
NR3C1	-0.003	0.088	-9999	-0.51	11	11
SUMO1/HDAC4	0.025	0.026	-9999	-0.35	1	1
SRF	0.012	0	-9999	-10000	0	0
HDAC4/YWHAB	0.016	0.03	-9999	-0.31	3	3
Tubulin	0.012	0.045	-9999	-0.31	7	7
HDAC4/14-3-3 E	0.017	0.024	-9999	-0.31	2	2
GNB1	0.012	0	-9999	-10000	0	0
RANGAP1	0.012	0	-9999	-10000	0	0
BCL6/BCoR	0.017	0.021	-9999	-0.38	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.024	0.021	-9999	-0.26	2	2
HDAC4/SRF	-0.001	0.088	-9999	-0.29	30	30
HDAC4/ER alpha	-0.036	0.14	-9999	-0.39	49	49
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.019	0.061	-9999	-0.34	3	3
cell motility	0.018	0.048	-9999	-0.29	8	8
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
HDAC7/HDAC3	0.017	0.017	-9999	-0.31	1	1
BCL6	0.011	0.029	-9999	-0.54	1	1
HDAC4/CaMK II delta B	0.01	0.034	-9999	-0.45	2	2
Hsp90/HDAC6	0.016	0.027	-9999	-0.35	2	2
ESR1	-0.059	0.18	-9999	-0.54	48	48
HDAC6/HDAC11	0.012	0.048	-9999	-0.33	7	7
Ran/GTP/Exportin 1	0.029	0.011	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	0.008	0.049	-9999	-0.54	3	3
RAN	0.012	0	-9999	-10000	0	0
HDAC4/MEF2C	0.033	0.032	-9999	-0.26	3	3
GNG2	-0.002	0.084	-9999	-0.48	11	11
NCOR2	0.012	0	-9999	-10000	0	0
TUBB2A	0.004	0.063	-9999	-0.45	7	7
HDAC11	0.006	0.056	-9999	-0.47	5	5
HSP90AA1	0.012	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
ANKRA2	0.012	0	-9999	-10000	0	0
RFXANK	0.011	0.024	-9999	-0.45	1	1
nuclear import	-0.024	0.018	-9999	-10000	0	0

×

mTOR 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	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	0.012	0	-10000	0	-10000	0	0
mol:PIP3	-0.022	0.092	0.27	7	-0.28	30	37
FRAP1	0.006	0.031	-10000	0	-10000	0	0
AKT1	0.001	0.086	0.22	7	-0.27	17	24
INSR	0.012	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0.014	-10000	0	-0.26	1	1
mol:GTP	0.008	0.069	-10000	0	-0.38	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.008	0.024	-10000	0	-10000	0	0
TSC2	0.012	0	-10000	0	-10000	0	0
RHEB/GDP	-0.018	0.054	-10000	0	-0.34	2	2
TSC1	0.011	0.029	-10000	0	-0.54	1	1
Insulin Receptor/IRS1	0	0.07	-10000	0	-0.34	15	15
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.009	0.029	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.012	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0.057	-10000	0	-0.28	3	3
MAP3K5	0.005	0.038	-10000	0	-0.28	6	6
PIK3R1	-0.018	0.12	-10000	0	-0.52	21	21
apoptosis	0.005	0.038	-10000	0	-0.28	6	6
mol:LY294002	0	0	-10000	0	-0.001	14	14
EIF4B	0.015	0.052	-10000	0	-0.27	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.016	0.047	-10000	0	-0.25	1	1
eIF4E/eIF4G1/eIF4A1	-0.004	0.016	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.007	0.094	-10000	0	-0.3	30	30
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.043	0.16	7	-0.18	2	9
FKBP1A	0.012	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.017	0.053	-10000	0	-0.33	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	14	14
FKBP12/Rapamycin	0.009	0.003	-10000	0	-10000	0	0
PDPK1	-0.02	0.084	0.22	7	-0.28	15	22
EIF4E	0.009	0.04	-10000	0	-0.54	2	2
ASK1/PP5C	0.01	0.06	-10000	0	-0.6	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.011	0.036	-10000	0	-0.46	2	2
TSC1/TSC2	0.009	0.074	-10000	0	-0.41	2	2
tumor necrosis factor receptor activity	0	0	0.001	14	-10000	0	14
RPS6	0.011	0.029	-10000	0	-0.54	1	1
PPP5C	0.012	0	-10000	0	-10000	0	0
EIF4G1	0.012	0	-10000	0	-10000	0	0
IRS1	-0.008	0.074	-10000	0	-0.35	16	16
INS	-0.001	0.024	-10000	0	-0.45	1	1
PTEN	0.002	0.075	-10000	0	-0.54	7	7
PDK2	-0.02	0.084	0.22	7	-0.28	15	22
EIF4EBP1	0.008	0.059	-10000	0	-1.1	1	1
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
PPP2R5D	0.012	0.029	-10000	0	-10000	0	0
peptide biosynthetic process	0.015	0.013	-10000	0	-0.23	1	1
RHEB	0.011	0.024	-10000	0	-0.45	1	1
EIF4A1	0.012	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	7	-0.002	2	9
EEF2	0.015	0.013	-10000	0	-0.23	1	1
eIF4E/4E-BP1	0.013	0.06	-10000	0	-1	1	1

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.039	0.095	-9999	-0.32	27	27
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.002	0.097	-9999	-0.3	27	27
SUMO1	0.011	0.029	-9999	-0.54	1	1
ZFPM1	0.001	0.074	-9999	-0.5	8	8
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.012	-9999	-0.21	1	1
FKBP3	0.006	0.057	-9999	-0.54	4	4
Histones	0.017	0.057	-9999	-10000	0	0
YY1/LSF	0.014	0.062	-9999	-0.3	9	9
SMG5	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.006	0.086	-9999	-0.25	27	27
I kappa B alpha/HDAC1	0.003	0.062	-9999	-0.28	1	1
SAP18	0.012	0	-9999	-10000	0	0
RELA	0	0.079	-9999	-0.23	27	27
HDAC1/Smad7	0.024	0.015	-9999	-0.26	1	1
RANGAP1	0.012	0	-9999	-10000	0	0
HDAC3/TR2	0.003	0.062	-9999	-0.28	1	1
NuRD/MBD3 Complex	0.04	0.016	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.006	0.072	-9999	-0.32	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.059	0.18	-9999	-0.53	49	49
GATA1	0	0.053	-9999	-0.45	5	5
Mad/Max	0.017	0.017	-9999	-0.31	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.042	0.032	-9999	-10000	0	0
RBBP7	0.011	0.024	-9999	-0.45	1	1
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.012	0	-9999	-10000	0	0
MAX	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
NFKBIA	-0.005	0.069	-9999	-0.31	1	1
KAT2B	0	0.08	-9999	-0.54	8	8
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.036	0.018	-9999	-10000	0	0
SIN3 complex	0.03	0.023	-9999	-0.28	2	2
SMURF1	0.011	0.024	-9999	-0.45	1	1
CHD3	0.011	0.029	-9999	-0.54	1	1
SAP30	0.009	0.04	-9999	-0.54	2	2
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.012	0	-9999	-10000	0	0
YY1/HDAC3	0.009	0.065	-9999	-0.36	1	1
YY1/HDAC2	0.022	0.037	-9999	-10000	0	0
YY1/HDAC1	0.022	0.037	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.04	0.016	-9999	-10000	0	0
PPARG	-0.063	0.15	-9999	-0.32	79	79
HDAC8/hEST1B	0.025	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.011	0.029	-9999	-0.54	1	1
HDAC3/SMRT (N-CoR2)	0.003	0.062	-9999	-0.28	1	1
MBD3L2	-0.006	0.062	-9999	-0.45	7	7
ubiquitin-dependent protein catabolic process	0.024	0.015	-9999	-0.26	1	1
CREBBP	0.012	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.041	0.022	-9999	-10000	0	0
HDAC1	0.012	0	-9999	-10000	0	0
HDAC3	-0.005	0.069	-9999	-0.31	1	1
HDAC2	0.012	0	-9999	-10000	0	0
YY1	0.02	0.043	-9999	-0.27	8	8
HDAC8	0.012	0	-9999	-10000	0	0
SMAD7	0.012	0	-9999	-10000	0	0
NCOR2	0.012	0	-9999	-10000	0	0
MXD1	0.011	0.024	-9999	-0.45	1	1
STAT3	0.022	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.021	0.058	-9999	-0.27	9	9
YY1/SAP30/HDAC1	0.027	0.041	-9999	-0.27	2	2
EP300	0.012	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.069	-9999	-0.31	1	1
histone deacetylation	0.04	0.015	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.058	-9999	-10000	0	0
nuclear export	-0.025	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GATAD2B	0.012	0	-9999	-10000	0	0
GATAD2A	0.012	0	-9999	-10000	0	0
GATA2/HDAC3	-0.037	0.12	-9999	-0.32	47	47
GATA1/HDAC1	0.01	0.038	-9999	-0.31	5	5
GATA1/HDAC3	-0.005	0.067	-9999	-0.28	1	1
CHD4	0.012	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.042	0.14	-9999	-0.35	60	60
SIN3/HDAC complex/Mad/Max	0.039	0.016	-9999	-10000	0	0
NuRD Complex	0.046	0.02	-9999	-10000	0	0
positive regulation of chromatin silencing	0.016	0.056	-9999	-10000	0	0
SIN3B	0.012	0	-9999	-10000	0	0
MTA2	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
SUMO1/HDAC1	0.026	0.019	-9999	-0.35	1	1
HDAC complex	0.031	0.013	-9999	-10000	0	0
GATA1/Fog1	0.002	0.065	-9999	-0.34	13	13
FKBP25/HDAC1/HDAC2	0.021	0.036	-9999	-0.32	4	4
TNF	-0.069	0.19	-9999	-0.49	60	60
negative regulation of cell growth	0.039	0.016	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.04	0.016	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.011	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.005	0.1	-9999	-0.32	27	27
SIN3/HDAC complex/NCoR1	0.038	0.015	-9999	-10000	0	0
TFCP2	-0.001	0.085	-9999	-0.54	9	9
NR2C1	0.012	0	-9999	-10000	0	0
MBD3	0.011	0.029	-9999	-0.54	1	1
MBD2	0.011	0.029	-9999	-0.54	1	1

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.016	0.064	-9999	-0.4	8	8
E-cadherin/beta catenin	0.01	0.059	-9999	-0.38	8	8
CTNNB1	0.011	0.029	-9999	-0.54	1	1
JUP	0.009	0.04	-9999	-0.54	2	2
CDH1	0.002	0.075	-9999	-0.54	7	7

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.059	0.043	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
RIP2/NOD2	0.006	0.069	-9999	-0.37	12	12
NFKBIA	0.038	0	-9999	-10000	0	0
BIRC2	0.009	0.04	-9999	-0.54	2	2
IKBKB	0.012	0	-9999	-10000	0	0
RIPK2	0.01	0.037	-9999	-0.5	2	2
IKBKG	0.031	0.043	-9999	-10000	0	0
IKK complex/A20	0.007	0.1	-9999	-0.41	5	5
NEMO/A20/RIP2	0.01	0.037	-9999	-0.49	2	2
XPO1	0.012	0	-9999	-10000	0	0
NEMO/ATM	0.035	0.043	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.017	0	-9999	-10000	0	0
IKK complex/ELKS	-0.006	0.027	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.021	0.032	-9999	-0.26	5	5
NOD2	-0.002	0.088	-9999	-0.53	10	10
NFKB1	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
MALT1	0.006	0.054	-9999	-0.45	5	5
cIAP1/UbcH5C	0.016	0.03	-9999	-0.38	2	2
ATM	0.011	0.029	-9999	-0.54	1	1
TNF/TNFR1A	-0.042	0.14	-9999	-0.35	60	60
TRAF6	0.012	0	-9999	-10000	0	0
PRKCA	-0.013	0.11	-9999	-0.53	17	17
CHUK	0.012	0	-9999	-10000	0	0
UBE2D3	0.012	0	-9999	-10000	0	0
TNF	-0.069	0.19	-9999	-0.49	60	60
NF kappa B1 p50/RelA	0.035	0	-9999	-10000	0	0
BCL10	0.012	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.038	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
TNFRSF1A	0.011	0.029	-9999	-0.54	1	1
IKK complex	0.042	0.04	-9999	-10000	0	0
CYLD	0.012	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.034	0.067	-9999	-0.36	1	1

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.011	0.029	-9999	-0.54	1	1
Aurora C/Aurora B/INCENP	0.011	0.06	-9999	-0.27	16	16
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.004	0.017	-9999	-10000	0	0
AURKB	0.005	0.064	-9999	-0.54	5	5
AURKC	-0.001	0.083	-9999	-0.5	10	10

×

Atypical NF-kappaB 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
BCL3/RelA	0.015	0.034	-9999	-0.36	3	3
FBXW11	0.012	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.022	0.023	-9999	-0.32	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.06	-9999	-0.46	2	2
NFKBIA	0.007	0.067	-9999	-0.24	20	20
MAPK14	0.012	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.024	0	-9999	-10000	0	0
ARRB2	0.015	0	-9999	-10000	0	0
REL	0.01	0.037	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.029	-9999	-0.3	3	3
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0	-9999	-10000	0	0
PIK3CA	0.01	0.034	-9999	-0.45	2	2
NF kappa B1 p50 dimer	0.018	0	-9999	-10000	0	0
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.014	0.062	-9999	-0.42	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.029	0.058	-9999	-0.45	2	2
SRC	0.009	0.04	-9999	-0.54	2	2
PI3K	-0.006	0.093	-9999	-0.37	23	23
NF kappa B1 p50/RelA	0.014	0.062	-9999	-0.42	2	2
IKBKB	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
SYK	0.001	0.079	-9999	-0.53	8	8
I kappa B alpha/PIK3R1	-0.002	0.092	-9999	-0.31	19	19
cell death	0.028	0.055	-9999	-0.43	2	2
NF kappa B1 p105/c-Rel	0.022	0.023	-9999	-0.32	1	1
LCK	-0.017	0.12	-9999	-0.5	21	21
BCL3	0.008	0.047	-9999	-0.51	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.044	0.14	-9999	-0.35	63	63
AKT1	0.043	0.097	-9999	-0.58	3	3
PTK2B	-0.006	0.12	-9999	-0.63	4	4
VEGFR2 homodimer/Frs2	0.025	0.056	-9999	-0.78	1	1
CAV1	0.006	0.056	-9999	-0.47	5	5
CALM1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.03	0.062	-9999	-0.79	1	1
endothelial cell proliferation	0.038	0.1	-9999	-0.44	6	6
mol:Ca2+	0.029	0.081	-9999	-0.66	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.036	0.059	-9999	-0.75	1	1
RP11-342D11.1	0.022	0.081	-9999	-0.67	2	2
CDH5	0.008	0.044	-9999	-0.48	3	3
VEGFA homodimer	0.029	0.028	-9999	-0.28	1	1
SHC1	0.012	0	-9999	-10000	0	0
SHC2	-0.035	0.14	-9999	-0.47	36	36
HRAS/GDP	-0.013	0.062	-9999	-0.51	3	3
SH2D2A	-0.009	0.1	-9999	-0.48	16	16
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.044	0.085	-9999	-0.65	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.018	0.085	-9999	-0.53	3	3
VEGFR1 homodimer	0.008	0.044	-9999	-0.48	3	3
SHC/GRB2/SOS1	-0.014	0.066	-9999	-0.63	2	2
GRB10	0.023	0.12	-9999	-0.62	9	9
PTPN11	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
PAK1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.038	0.072	-9999	-0.72	2	2
HRAS	0.011	0.024	-9999	-0.45	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.01	0.078	-9999	-0.43	3	3
HIF1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.035	0.058	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.01	0.037	-9999	-0.5	2	2
Nck/Pak	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.029	0.063	-9999	-0.79	1	1
mol:GDP	-0.014	0.064	-9999	-0.61	2	2
mol:NADP	0.044	0.076	-9999	-0.49	3	3
eNOS/Hsp90	0.047	0.072	-9999	-0.72	1	1
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
mol:IP3	0.029	0.082	-9999	-0.67	2	2
HIF1A/ARNT	0.018	0	-9999	-10000	0	0
SHB	0.011	0.029	-9999	-0.54	1	1
VEGFA	0.009	0.042	-9999	-0.45	3	3
VEGFC	0.002	0.075	-9999	-0.54	7	7
FAK1/Vinculin	0.02	0.099	-9999	-0.71	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.01	0.12	-9999	-0.61	4	4
PTPN6	0.008	0.049	-9999	-0.54	3	3
EPAS1	0.014	0.055	-9999	-0.48	4	4
mol:L-citrulline	0.044	0.076	-9999	-0.49	3	3
ITGAV	0.005	0.062	-9999	-0.52	5	5
PIK3CA	0.01	0.034	-9999	-0.45	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.036	0.059	-9999	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer	0.026	0.089	-9999	-0.73	2	2
VEGFR2/3 heterodimer	0.023	0.069	-9999	-1.1	1	1
VEGFB	0.012	0	-9999	-10000	0	0
MAPK11	0.029	0.086	-9999	-0.69	2	2
VEGFR2 homodimer	0.022	0.064	-9999	-0.47	5	5
FLT1	0.008	0.044	-9999	-0.48	3	3
NEDD4	0.002	0.075	-9999	-0.54	7	7
MAPK3	0.021	0.088	-9999	-0.65	2	2
MAPK1	0.021	0.088	-9999	-0.49	4	4
VEGFA145/NRP2	0	0.087	-9999	-0.38	18	18
VEGFR1/2 heterodimer	0.022	0.073	-9999	-0.81	2	2
KDR	0.022	0.065	-9999	-0.48	5	5
VEGFA165/NRP1/VEGFR2 homodimer	0.019	0.1	-9999	-0.55	5	5
SRC	0.009	0.04	-9999	-0.54	2	2
platelet activating factor biosynthetic process	0.023	0.089	-9999	-0.66	2	2
PI3K	0.034	0.11	-9999	-0.65	4	4
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.03	0.062	-9999	-0.79	1	1
FES	0.027	0.087	-9999	-0.68	2	2
GAB1	0.04	0.081	-9999	-0.72	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.028	0.066	-9999	-0.79	1	1
CTNNB1	0.011	0.029	-9999	-0.54	1	1
SOS1	0.012	0	-9999	-10000	0	0
ARNT	0.012	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.045	0.079	-9999	-0.5	3	3
VEGFR2 homodimer/VEGFA homodimer/Yes	0.029	0.064	-9999	-0.79	1	1
PI3K/GAB1	0.04	0.11	-9999	-0.56	5	5
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.041	0.057	-9999	-0.72	1	1
PRKACA	0.012	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.023	0.08	-9999	-0.77	2	2
HSP90AA1	0.012	0	-9999	-10000	0	0
CDC42	0.029	0.083	-9999	-0.68	2	2
actin cytoskeleton reorganization	0.018	0.084	-9999	-0.53	3	3
PTK2	0.014	0.1	-9999	-0.66	3	3
EDG1	0.022	0.081	-9999	-0.67	2	2
mol:DAG	0.029	0.082	-9999	-0.67	2	2
CaM/Ca2+	0.033	0.076	-9999	-0.62	2	2
MAP2K3	0.028	0.09	-9999	-0.6	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.026	0.12	-9999	-0.63	9	9
PLCG1	0.029	0.083	-9999	-0.68	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.034	0.066	-9999	-0.57	2	2
IQGAP1	0.012	0	-9999	-10000	0	0
YES1	0.011	0.029	-9999	-0.54	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.03	0.062	-9999	-0.79	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.027	0.068	-9999	-0.79	1	1
cell migration	0.04	0.088	-9999	-0.81	1	1
mol:PI-3-4-5-P3	0.034	0.1	-9999	-0.58	4	4
FYN	0.011	0.024	-9999	-0.45	1	1
VEGFB/NRP1	0.028	0.077	-9999	-0.63	2	2
mol:NO	0.044	0.076	-9999	-0.49	3	3
PXN	0.012	0	-9999	-10000	0	0
HRAS/GTP	-0.013	0.062	-9999	-0.51	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.025	0.12	-9999	-0.63	9	9
VHL	0.011	0.029	-9999	-0.54	1	1
ITGB3	-0.068	0.18	-9999	-0.48	60	60
NOS3	0.044	0.085	-9999	-0.58	3	3
VEGFR2 homodimer/VEGFA homodimer/Sck	0.004	0.1	-9999	-0.58	2	2
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	0.021	0.098	-9999	-0.56	4	4
PRKCB	0.015	0.11	-9999	-0.56	5	5
VCL	0.012	0	-9999	-10000	0	0
VEGFA165/NRP1	0.023	0.081	-9999	-0.67	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	0.028	0.077	-9999	-0.78	2	2
VEGFA165/NRP2	0	0.087	-9999	-0.38	18	18
MAPKKK cascade	0.043	0.1	-9999	-0.51	9	9
NRP2	-0.011	0.11	-9999	-0.52	16	16
VEGFC homodimer	0.002	0.075	-9999	-0.54	7	7
NCK1	0.012	0	-9999	-10000	0	0
ROCK1	0.012	0	-9999	-10000	0	0
FAK1/Paxillin	0.02	0.099	-9999	-0.71	2	2
MAP3K13	0.023	0.095	-9999	-0.63	3	3
PDPK1	0.039	0.09	-9999	-0.56	3	3

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.025	0.07	-9999	-0.44	8	8
KLHL20	-0.013	0.049	-9999	-0.25	5	5
CYFIP2	-0.001	0.085	-9999	-0.54	9	9
Rac1/GDP	0.041	0.052	-9999	-0.28	2	2
ENAH	0.022	0.074	-9999	-0.44	8	8
AP1M1	0.012	0	-9999	-10000	0	0
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.011	0.029	-9999	-0.54	1	1
CDC42/GTP	-0.005	0.029	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.012	0.036	-9999	-0.19	5	5
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.018	0.063	-9999	-0.28	14	14
RAPGEF1	0.034	0.063	-9999	-0.37	8	8
CTNND1	0.012	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.071	-9999	-0.46	8	8
CRK	0.029	0.068	-9999	-0.41	8	8
E-cadherin/gamma catenin/alpha catenin	0.017	0.062	-9999	-0.41	7	7
alphaE/beta7 Integrin	0.01	0.056	-9999	-0.37	8	8
IQGAP1	0.012	0	-9999	-10000	0	0
NCKAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.023	0.016	-9999	-0.29	1	1
DLG1	0.025	0.069	-9999	-0.44	8	8
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.036	-9999	-0.25	2	2
MLLT4	0.011	0.029	-9999	-0.54	1	1
ARF6/GTP/NME1/Tiam1	0.017	0.046	-9999	-0.29	8	8
PI3K	-0.013	0.046	-9999	-0.33	2	2
ARF6	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.009	0.07	-9999	-0.48	7	7
TIAM1	0	0.08	-9999	-0.54	8	8
E-cadherin(dimer)/Ca2+	0.023	0.043	-9999	-0.27	8	8
AKT1	-0.008	0.027	-9999	-0.18	2	2
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
CDH1	0.002	0.075	-9999	-0.54	7	7
RhoA/GDP	0.041	0.052	-9999	-10000	0	0
actin cytoskeleton organization	0.024	0.046	-9999	-0.18	5	5
CDC42/GDP	0.041	0.052	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.015	0.049	-9999	-0.32	7	7
ITGB7	0.001	0.077	-9999	-0.52	8	8
RAC1	0.012	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.025	0.046	-9999	-0.28	8	8
E-cadherin/Ca2+/beta catenin/alpha catenin	0.016	0.043	-9999	-0.27	8	8
mol:GDP	0.038	0.058	-9999	-0.31	4	4
CDC42/GTP/IQGAP1	0.017	0	-9999	-10000	0	0
JUP	0.009	0.04	-9999	-0.54	2	2
p120 catenin/RhoA/GDP	0.039	0.052	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.017	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.018	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
CDC42	0.012	0	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.014	0.055	-9999	-0.21	18	18
NME1	0.012	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.025	0.069	-9999	-0.44	8	8
regulation of cell-cell adhesion	-0.004	0.026	-9999	-10000	0	0
WASF2	-0.006	0.019	-9999	-10000	0	0
Rap1/GTP	-0.006	0.033	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.023	0.068	-9999	-0.54	2	2
CCND1	0.016	0.068	-9999	-0.26	18	18
VAV2	0.024	0.11	-9999	-0.52	12	12
RAP1/GDP	0.039	0.046	-9999	-10000	0	0
adherens junction assembly	0.025	0.067	-9999	-0.42	8	8
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.012	0	-9999	-10000	0	0
PIP5K1C	0.012	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.027	0.066	-9999	-0.51	2	2
E-cadherin/beta catenin	-0.007	0.049	-9999	-0.36	7	7
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.023	0.072	-9999	-0.44	8	8
PIK3CA	0.01	0.034	-9999	-0.45	2	2
Rac1/GTP	-0.023	0.077	-9999	-0.43	5	5
E-cadherin/beta catenin/alpha catenin	0.018	0.05	-9999	-0.32	8	8
ITGAE	0.012	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.019	0.073	-9999	-0.47	8	8

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.019	0.08	-10000	0	-0.39	4	4
adherens junction organization	0.022	0.067	-10000	0	-0.48	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.084	-10000	0	-0.38	6	6
FMN1	0.016	0.078	-10000	0	-0.43	6	6
mol:IP3	0.015	0.073	-10000	0	-0.38	4	4
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.018	0.066	-10000	0	-0.5	4	4
CTNNB1	0.011	0.029	-10000	0	-0.54	1	1
AKT1	0.02	0.076	-10000	0	-0.41	4	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.022	0.078	-10000	0	-0.44	10	10
CTNND1	0.012	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.022	0.064	-10000	0	-0.46	4	4
VASP	0.023	0.064	-10000	0	-0.48	4	4
ZYX	0.024	0.063	-10000	0	-0.48	4	4
JUB	0.023	0.064	-10000	0	-0.48	4	4
EGFR(dimer)	0.016	0.079	-10000	0	-0.42	6	6
E-cadherin/beta catenin-gamma catenin	0.015	0.061	-10000	0	-0.38	8	8
mol:PI-3-4-5-P3	0.015	0.079	-10000	0	-0.43	4	4
PIK3CA	0.01	0.034	-10000	0	-0.45	2	2
PI3K	0.015	0.08	-10000	0	-0.44	4	4
FYN	0.012	0.08	-10000	0	-0.32	6	6
mol:Ca2+	0.015	0.072	-10000	0	-0.37	4	4
JUP	0.009	0.04	-10000	0	-0.53	2	2
PIK3R1	-0.017	0.12	-10000	0	-0.52	21	21
mol:DAG	0.015	0.073	-10000	0	-0.38	4	4
CDH1	0.001	0.075	-10000	0	-0.54	7	7
RhoA/GDP	0.02	0.084	-10000	0	-0.38	6	6
establishment of polarity of embryonic epithelium	0.023	0.063	-10000	0	-0.46	4	4
SRC	0.009	0.04	-10000	0	-0.54	2	2
RAC1	0.012	0	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
EGFR	-0.004	0.092	-10000	0	-0.53	11	11
CASR	0.003	0.088	-10000	0	-0.36	6	6
RhoA/GTP	0.02	0.067	-10000	0	-0.34	4	4
AKT2	0.02	0.076	-10000	0	-0.41	4	4
actin cable formation	0.02	0.077	-10000	0	-0.41	6	6
apoptosis	-0.018	0.077	0.41	4	-10000	0	4
CTNNA1	0.012	0.003	-10000	0	-10000	0	0
mol:GDP	0.014	0.088	-10000	0	-0.4	6	6
PIP5K1A	0.022	0.065	-10000	0	-0.48	4	4
PLCG1	0.015	0.075	-10000	0	-0.39	4	4
Rac1/GTP	0.02	0.073	-10000	0	-0.39	6	6
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.035	-9999	-0.3	3	3
BIRC5	-0.008	0.1	-9999	-0.53	14	14
NFKBIA	0.024	0.021	-9999	-10000	0	0
CPEB1	-0.03	0.14	-9999	-0.48	31	31
AKT1	0.023	0.026	-9999	-0.26	1	1
NDEL1	0.012	0	-9999	-10000	0	0
Aurora A/BRCA1	0.019	0.029	-9999	-0.29	2	2
NDEL1/TACC3	0.025	0.028	-9999	-10000	0	0
GADD45A	0.008	0.047	-9999	-0.51	3	3
GSK3B	0.012	0.008	-9999	-10000	0	0
PAK1/Aurora A	0.023	0.021	-9999	-10000	0	0
MDM2	0.009	0.04	-9999	-0.54	2	2
JUB	0.011	0.024	-9999	-0.45	1	1
TPX2	0.013	0.05	-9999	-0.37	6	6
TP53	0.01	0.071	-9999	-0.3	17	17
DLG7	0.016	0.021	-9999	-0.2	1	1
AURKAIP1	0.012	0	-9999	-10000	0	0
ARHGEF7	0.012	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.027	0.029	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.029	-9999	-0.29	2	2
AURKA	0.02	0.026	-9999	-0.24	1	1
AURKB	0.005	0.057	-9999	-0.28	11	11
CDC25B	0.023	0.026	-9999	-10000	0	0
G2/M transition checkpoint	0.019	0.022	-9999	-0.23	1	1
mRNA polyadenylation	-0.004	0.076	-9999	-0.24	31	31
Aurora A/CPEB	-0.004	0.076	-9999	-0.25	31	31
Aurora A/TACC1/TRAP/chTOG	0.031	0.038	-9999	-10000	0	0
BRCA1	0.009	0.04	-9999	-0.54	2	2
centrosome duplication	0.023	0.021	-9999	-10000	0	0
regulation of centrosome cycle	0.025	0.027	-9999	-10000	0	0
spindle assembly	0.03	0.038	-9999	-10000	0	0
TDRD7	0.009	0.04	-9999	-0.54	2	2
Aurora A/RasGAP/Survivin	0.021	0.061	-9999	-0.4	2	2
CENPA	0.006	0.066	-9999	-0.39	9	9
Aurora A/PP2A	0.023	0.021	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.023	0.035	-9999	-10000	0	0
negative regulation of DNA binding	0.01	0.07	-9999	-0.3	17	17
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.018	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
Ajuba/Aurora A	0.02	0.023	-9999	-0.23	1	1
mitotic prometaphase	0.001	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.026	-9999	-0.24	1	1
TACC1	0.007	0.05	-9999	-0.47	4	4
TACC3	0.009	0.042	-9999	-0.45	3	3
Aurora A/Antizyme1	0.029	0.019	-9999	-10000	0	0
Aurora A/RasGAP	0.023	0.021	-9999	-10000	0	0
OAZ1	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.012	0.008	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.025	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.013	0.05	-9999	-0.37	6	6
PPP2R5D	0.012	0	-9999	-10000	0	0
Aurora A/TPX2	0.023	0.046	-9999	-0.45	2	2
PAK1	0.012	0	-9999	-10000	0	0
CKAP5	0.012	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.019	0.066	-10000	0	-0.38	2	2
CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
AKT1	0.011	0.024	-10000	0	-0.45	1	1
AKT2	0.011	0.024	-10000	0	-0.45	1	1
STXBP4	0.009	0.04	-10000	0	-0.54	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.016	0.074	0.2	5	-0.42	2	7
YWHAZ	0.012	0	-10000	0	-10000	0	0
CALM1	0.012	0	-10000	0	-10000	0	0
YWHAQ	0.012	0	-10000	0	-10000	0	0
TBC1D4	0.006	0.071	-10000	0	-0.38	12	12
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.012	0	-10000	0	-10000	0	0
YWHAB	0.011	0.024	-10000	0	-0.45	1	1
SNARE/Synip	0.022	0.029	-10000	0	-0.3	3	3
YWHAG	0.012	0	-10000	0	-10000	0	0
ASIP	0.001	0.058	-10000	0	-0.45	6	6
PRKCI	0.008	0.044	-10000	0	-0.48	3	3
AS160/CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
RHOQ	0.012	0	-10000	0	-10000	0	0
GYS1	0.025	0.013	-10000	0	-10000	0	0
PRKCZ	0.009	0.04	-10000	0	-0.54	2	2
TRIP10	0.011	0.029	-10000	0	-0.54	1	1
TC10/GTP/CIP4/Exocyst	0.016	0.018	-10000	0	-0.33	1	1
AS160/14-3-3	0.01	0.071	-10000	0	-10000	0	0
VAMP2	0.012	0	-10000	0	-10000	0	0
SLC2A4	0.015	0.08	-10000	0	-0.36	5	5
STX4	0.011	0.024	-10000	0	-0.45	1	1
GSK3B	0.021	0.015	-10000	0	-10000	0	0
SFN	-0.056	0.18	-10000	0	-0.51	49	49
LNPEP	0.012	0	-10000	0	-10000	0	0
YWHAE	0.012	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.019	0.017	-10000	0	-0.31	1	1
BAD/BCL-XL/YWHAZ	0.029	0.013	-10000	0	-10000	0	0
CDKN1B	0.015	0.068	-10000	0	-0.36	4	4
CDKN1A	0.016	0.067	-10000	0	-0.4	3	3
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.009	0.04	-10000	0	-0.54	2	2
FOXO3	0.028	0.034	-10000	0	-0.4	2	2
AKT1	0.023	0.036	-10000	0	-0.43	2	2
BAD	0.012	0	-10000	0	-10000	0	0
AKT3	0.007	0.044	-10000	0	-0.22	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.028	0.034	-10000	0	-0.4	2	2
AKT1/ASK1	0.023	0.045	-10000	0	-0.39	2	2
BAD/YWHAZ	0.025	0	-10000	0	-10000	0	0
RICTOR	0.009	0.04	-10000	0	-0.54	2	2
RAF1	0.012	0	-10000	0	-10000	0	0
JNK cascade	-0.022	0.044	0.38	2	-10000	0	2
TSC1	0.027	0.037	-10000	0	-0.4	2	2
YWHAZ	0.012	0	-10000	0	-10000	0	0
AKT1/RAF1	0.029	0.034	-10000	0	-0.4	2	2
EP300	0.012	0	-10000	0	-10000	0	0
mol:GDP	0.023	0.036	-10000	0	-0.42	2	2
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.028	0.034	-10000	0	-0.4	2	2
YWHAQ	0.012	0	-10000	0	-10000	0	0
TBC1D4	0.01	0.058	-10000	0	-0.32	11	11
MAP3K5	0.004	0.064	-10000	0	-0.5	6	6
MAPKAP1	0.012	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.019	0.045	-10000	0	-10000	0	0
YWHAH	0.012	0	-10000	0	-10000	0	0
AKT1S1	0.028	0.034	-10000	0	-0.4	2	2
CASP9	0.027	0.036	-10000	0	-0.4	2	2
YWHAB	0.011	0.024	-10000	0	-0.45	1	1
p27Kip1/KPNA1	0.021	0.066	-10000	0	-0.34	4	4
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.023	0.025	-10000	0	-0.32	2	2
YWHAE	0.012	0	-10000	0	-10000	0	0
SRC	0.009	0.04	-10000	0	-0.54	2	2
AKT2/p21CIP1	0.02	0.064	-10000	0	-0.36	3	3
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.012	-10000	0	-10000	0	0
CHUK	0.028	0.034	-10000	0	-0.4	2	2
BAD/BCL-XL	0.039	0.035	-10000	0	-0.37	2	2
mTORC2	0.014	0.023	-10000	0	-0.3	2	2
AKT2	0.014	0.011	-10000	0	-0.19	1	1
FOXO1-3a-4/14-3-3 family	0.03	0.054	-10000	0	-10000	0	0
PDPK1	0.012	0	-10000	0	-10000	0	0
MDM2	0.026	0.041	-10000	0	-0.37	3	3
MAPKKK cascade	-0.028	0.034	0.4	2	-10000	0	2
MDM2/Cbp/p300	0.038	0.039	-10000	0	-0.36	2	2
TSC1/TSC2	0.032	0.036	-10000	0	-0.39	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.037	-10000	0	-0.35	2	2
glucose import	-0.011	0.093	-10000	0	-0.28	26	26
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.024	0.022	-10000	0	-0.24	2	2
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.011	0.094	-10000	0	-0.28	26	26
GSK3A	0.028	0.034	-10000	0	-0.4	2	2
FOXO1	0.027	0.036	-10000	0	-0.4	2	2
GSK3B	0.028	0.034	-10000	0	-0.4	2	2
SFN	-0.056	0.18	-10000	0	-0.51	49	49
G1/S transition of mitotic cell cycle	0.033	0.033	-10000	0	-0.39	2	2
p27Kip1/14-3-3 family	0.016	0.062	-10000	0	-10000	0	0
PRKACA	0.012	0	-10000	0	-10000	0	0
KPNA1	0.012	0	-10000	0	-10000	0	0
HSP90AA1	0.012	0	-10000	0	-10000	0	0
YWHAG	0.012	0	-10000	0	-10000	0	0
RHEB	0.011	0.024	-10000	0	-0.45	1	1
CREBBP	0.012	0	-10000	0	-10000	0	0

×

FoxO family signaling

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
G6PC	0.026	0.064	-9999	-10000	0	0
PLK1	0.054	0.17	-9999	-0.93	6	6
CDKN1B	0.077	0.14	-9999	-0.48	18	18
FOXO3	0.058	0.14	-9999	-0.62	5	5
KAT2B	0.008	0.082	-9999	-0.54	8	8
FOXO1/SIRT1	0.005	0.047	-9999	-0.52	1	1
CAT	0.06	0.13	-9999	-0.62	3	3
CTNNB1	0.011	0.029	-9999	-0.54	1	1
AKT1	0.02	0.03	-9999	-0.49	1	1
FOXO1	0.03	0.039	-9999	-10000	0	0
MAPK10	0.004	0.088	-9999	-0.27	31	31
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.068	0.066	-9999	-0.38	2	2
response to oxidative stress	0.01	0.014	-9999	-10000	0	0
FOXO3A/SIRT1	-0.005	0.098	-9999	-0.55	6	6
XPO1	0.013	0	-9999	-10000	0	0
EP300	0.013	0.005	-9999	-10000	0	0
BCL2L11	0.028	0.028	-9999	-10000	0	0
FOXO1/SKP2	0.032	0.035	-9999	-10000	0	0
mol:GDP	0.01	0.014	-9999	-10000	0	0
RAN	0.014	0.001	-9999	-10000	0	0
GADD45A	0.08	0.099	-9999	-0.93	2	2
YWHAQ	0.012	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.046	0.052	-9999	-10000	0	0
MST1	-0.002	0.1	-9999	-0.48	16	16
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.019	0.086	-9999	-10000	0	0
YWHAB	0.011	0.024	-9999	-0.45	1	1
MAPK8	0.032	0.024	-9999	-0.28	2	2
MAPK9	0.033	0.009	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
SIRT1	0.01	0.043	-9999	-0.54	2	2
SOD2	0.095	0.11	-9999	-0.59	4	4
RBL2	0.069	0.12	-9999	-1.1	1	1
RAL/GDP	0.028	0.011	-9999	-10000	0	0
CHUK	0.02	0.012	-9999	-10000	0	0
Ran/GTP	0.013	0.002	-9999	-10000	0	0
CSNK1G2	0.012	0	-9999	-10000	0	0
RAL/GTP	0.033	0.012	-9999	-10000	0	0
CSNK1G1	0.012	0	-9999	-10000	0	0
FASLG	-0.076	0.35	-9999	-1.4	25	25
SKP2	0.012	0	-9999	-10000	0	0
USP7	0.014	0.001	-9999	-10000	0	0
IKBKB	0.02	0.012	-9999	-10000	0	0
CCNB1	0.059	0.14	-9999	-0.85	3	3
FOXO1-3a-4/beta catenin	0.097	0.11	-9999	-0.41	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.035	-9999	-10000	0	0
CSNK1A1	0.012	0	-9999	-10000	0	0
SGK1	0.005	0.085	-9999	-0.48	11	11
CSNK1G3	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.022	0.004	-9999	-10000	0	0
ZFAND5	0.07	0.058	-9999	-10000	0	0
SFN	-0.056	0.18	-9999	-0.51	49	49
CDK2	0.012	0.008	-9999	-10000	0	0
FOXO3A/14-3-3	0.03	0.082	-9999	-0.33	3	3
CREBBP	0.012	0.008	-9999	-10000	0	0
FBXO32	0.053	0.16	-9999	-1.1	3	3
BCL6	0.069	0.12	-9999	-1.1	1	1
RALB	0.013	0.001	-9999	-10000	0	0
RALA	0.013	0.001	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0.045	-9999	-0.45	3	3
VEGFR1 homodimer/NRP1	0.016	0.045	-9999	-0.45	3	3
mol:DAG	0.02	0.067	-9999	-0.57	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.021	0.047	-9999	-0.41	3	3
CaM/Ca2+	0.026	0.063	-9999	-0.53	2	2
HIF1A	0.017	0.025	-9999	-0.34	1	1
GAB1	0.011	0.029	-9999	-0.54	1	1
AKT1	0.02	0.095	-9999	-0.52	4	4
PLCG1	0.02	0.067	-9999	-0.57	2	2
NOS3	0.031	0.08	-9999	-0.7	2	2
CBL	0.012	0	-9999	-10000	0	0
mol:NO	0.032	0.077	-9999	-0.66	2	2
FLT1	0.022	0.052	-9999	-0.52	3	3
PGF	-0.006	0.091	-9999	-0.46	14	14
VEGFR1 homodimer/NRP2/VEGFR121	0.016	0.082	-9999	-0.55	3	3
CALM1	0.012	0	-9999	-10000	0	0
PIK3CA	0.01	0.034	-9999	-0.45	2	2
eNOS/Hsp90	0.037	0.075	-9999	-0.63	2	2
endothelial cell proliferation	0.005	0.11	-9999	-0.55	6	6
mol:Ca2+	0.02	0.066	-9999	-0.56	2	2
MAPK3	0.017	0.087	-9999	-0.48	5	5
MAPK1	0.017	0.087	-9999	-0.48	5	5
PIK3R1	-0.018	0.12	-9999	-0.52	21	21
PLGF homodimer	-0.006	0.091	-9999	-0.46	14	14
PRKACA	0.012	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.006	0.056	-9999	-0.47	5	5
VEGFA homodimer	0.009	0.041	-9999	-0.45	3	3
VEGFR1 homodimer/VEGFA homodimer	0.023	0.051	-9999	-0.45	3	3
platelet activating factor biosynthetic process	0.021	0.085	-9999	-0.46	5	5
PI3K	0.011	0.099	-9999	-0.57	4	4
PRKCA	0.012	0.091	-9999	-0.51	5	5
PRKCB	0.005	0.1	-9999	-0.53	5	5
VEGFR1 homodimer/PLGF homodimer	0.014	0.074	-9999	-0.53	3	3
VEGFA	0.009	0.042	-9999	-0.45	3	3
VEGFB	0.012	0	-9999	-10000	0	0
mol:IP3	0.02	0.067	-9999	-0.57	2	2
RASA1	0.03	0.041	-9999	-0.62	1	1
NRP2	-0.011	0.11	-9999	-0.52	16	16
VEGFR1 homodimer	0.022	0.051	-9999	-0.52	3	3
VEGFB homodimer	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.034	0.085	-9999	-0.62	3	3
PTPN11	0.012	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.01	0.098	-9999	-0.56	4	4
mol:L-citrulline	0.032	0.077	-9999	-0.66	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.027	0.067	-9999	-0.59	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.047	-9999	-0.62	1	1
CD2AP	-0.004	0.093	-9999	-0.54	11	11
PI3K/GAB1	0.015	0.096	-9999	-0.55	4	4
PDPK1	0.014	0.093	-9999	-0.53	4	4
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.047	-9999	-0.62	1	1
mol:NADP	0.032	0.077	-9999	-0.66	2	2
HSP90AA1	0.012	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.026	0.066	-9999	-0.58	1	1
VEGFR1 homodimer/NRP2	0.011	0.083	-9999	-0.53	3	3

×

Circadian rhythm 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
chromatin modification	0.039	0.019	-10000	0	-10000	0	0
CLOCK	0.014	0.029	-10000	0	-0.53	1	1
TIMELESS/CRY2	0.034	0.02	-10000	0	-10000	0	0
DEC1/BMAL1	0.011	0.021	-10000	0	-0.38	1	1
ATR	0.012	0	-10000	0	-10000	0	0
NR1D1	0.031	0.028	-10000	0	-10000	0	0
ARNTL	0.014	0.029	-10000	0	-0.53	1	1
TIMELESS	0.031	0.022	-10000	0	-10000	0	0
NPAS2	-0.012	0.12	-10000	0	-0.52	19	19
CRY2	0.012	0	-10000	0	-10000	0	0
mol:CO	-0.012	0.004	0.072	1	-10000	0	1
CHEK1	0.012	0	-10000	0	-10000	0	0
mol:HEME	0.012	0.004	-10000	0	-0.072	1	1
PER1	0.011	0.024	-10000	0	-0.45	1	1
BMAL/CLOCK/NPAS2	0.02	0.079	-10000	0	-0.3	21	21
BMAL1/CLOCK	0.036	0.041	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.039	0.019	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.039	0.019	-10000	0	-10000	0	0
mol:NADPH	0.012	0.004	-10000	0	-0.072	1	1
PER1/TIMELESS	0.033	0.023	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.002	0.004	-10000	0	-10000	0	0

×

Arf6 downstream 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.027	0.086	-10000	0	-1.1	2	2
regulation of axonogenesis	-0.021	0.025	-10000	0	-10000	0	0
myoblast fusion	-0.013	0.042	0.39	3	-10000	0	3
mol:GTP	0.008	0.022	-10000	0	-0.21	3	3
regulation of calcium-dependent cell-cell adhesion	-0.022	0.053	0.3	8	-10000	0	8
ARF1/GTP	0.015	0.017	-10000	0	-10000	0	0
mol:GM1	0.007	0.017	-10000	0	-0.17	2	2
mol:Choline	0.02	0.03	-10000	0	-0.26	3	3
lamellipodium assembly	-0.004	0.041	-10000	0	-0.4	3	3
MAPK3	0.021	0.035	-10000	0	-0.32	3	3
ARF6/GTP/NME1/Tiam1	0.023	0.053	-10000	0	-0.31	8	8
ARF1	0.012	0	-10000	0	-10000	0	0
ARF6/GDP	0.013	0.042	-10000	0	-0.39	3	3
ARF1/GDP	0.02	0.039	-10000	0	-0.36	3	3
ARF6	0.011	0.012	-10000	0	-10000	0	0
RAB11A	0.012	0	-10000	0	-10000	0	0
TIAM1	0.002	0.08	-10000	0	-0.54	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.035	-10000	0	-0.32	3	3
actin filament bundle formation	-0.018	0.038	0.36	3	-10000	0	3
KALRN	-0.007	0.051	-10000	0	-0.31	9	9
RAB11FIP3/RAB11A	0.018	0	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.038	-10000	0	-0.36	3	3
NME1	0.014	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.038	-10000	0	-0.36	3	3
substrate adhesion-dependent cell spreading	0.008	0.022	-10000	0	-0.21	3	3
cortical actin cytoskeleton organization	-0.004	0.041	-10000	0	-0.4	3	3
RAC1	0.012	0	-10000	0	-10000	0	0
liver development	0.008	0.022	-10000	0	-0.21	3	3
ARF6/GTP	0.008	0.022	-10000	0	-0.21	3	3
RhoA/GTP	0.015	0.017	-10000	0	-10000	0	0
mol:GDP	-0.004	0.041	-10000	0	-0.39	3	3
ARF6/GTP/RAB11FIP3/RAB11A	0.023	0.015	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
PLD1	0.015	0.028	-10000	0	-0.29	2	2
RAB11FIP3	0.012	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.041	-10000	0	-0.4	3	3
ruffle organization	0.021	0.025	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.008	0.022	-10000	0	-0.21	3	3
PLD2	0.016	0.026	-10000	0	-0.36	1	1
PIP5K1A	0.021	0.025	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.02	0.03	-10000	0	-0.26	3	3
Rac1/GTP	-0.004	0.041	-10000	0	-0.4	3	3

×

PLK1 signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.047	0.24	13	-10000	0	13
BUB1B	0.015	0.049	-10000	0	-0.39	5	5
PLK1	0.014	0.017	-10000	0	-0.14	3	3
PLK1S1	0.007	0.029	-10000	0	-0.26	2	2
KIF2A	0.019	0.016	-10000	0	-0.17	1	1
regulation of mitotic centrosome separation	0.014	0.017	-10000	0	-0.14	3	3
GOLGA2	0.012	0	-10000	0	-10000	0	0
Hec1/SPC24	0.006	0.091	-10000	0	-0.32	24	24
WEE1	0.02	0.017	-10000	0	-0.23	1	1
cytokinesis	0.025	0.037	-10000	0	-0.44	2	2
PP2A-alpha B56	0.017	0.1	-10000	0	-0.62	9	9
AURKA	0.011	0.028	-10000	0	-0.29	3	3
PICH/PLK1	0.026	0.041	-10000	0	-0.32	4	4
CENPE	0.011	0.057	-10000	0	-0.3	11	11
RhoA/GTP	0.009	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.019	0.015	-10000	0	-0.16	1	1
PPP2CA	0.012	0	-10000	0	-10000	0	0
FZR1	0.012	0	-10000	0	-10000	0	0
TPX2	0.009	0.038	-10000	0	-0.31	5	5
PAK1	0.012	0	-10000	0	-10000	0	0
SPC24	-0.014	0.12	-10000	0	-0.53	18	18
FBXW11	0.012	0	-10000	0	-10000	0	0
CLSPN	0.001	0.06	-10000	0	-0.31	12	12
GORASP1	0.012	0	-10000	0	-10000	0	0
metaphase	0	0.002	-10000	0	-0.019	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.008	-10000	0	-0.071	2	2
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-0.012	3	3
STAG2	0.009	0.04	-10000	0	-0.54	2	2
GRASP65/GM130/RAB1/GTP	0.001	0.004	-10000	0	-10000	0	0
spindle elongation	0.014	0.017	-10000	0	-0.14	3	3
ODF2	0.012	0.001	-10000	0	-10000	0	0
BUB1	-0.017	0.11	-10000	0	-0.69	9	9
TPT1	0.013	0.008	-10000	0	-10000	0	0
CDC25C	0.01	0.048	-10000	0	-0.44	4	4
CDC25B	0.009	0.041	-10000	0	-0.45	3	3
SGOL1	0.001	0.048	-10000	0	-0.24	13	13
RHOA	0.012	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.003	0.028	-10000	0	-0.44	1	1
CDC14B	0.005	0.042	-10000	0	-0.4	4	4
CDC20	0.008	0.047	-10000	0	-0.51	3	3
PLK1/PBIP1	0.015	0.024	-10000	0	-0.26	2	2
mitosis	0	0.004	0.039	3	-10000	0	3
FBXO5	0.014	0.036	-10000	0	-0.25	6	6
CDC2	0.001	0.001	-10000	0	-0.019	1	1
NDC80	-0.001	0.085	-10000	0	-0.54	9	9
metaphase plate congression	0.013	0.011	-10000	0	-10000	0	0
ERCC6L	0.025	0.041	-10000	0	-0.32	4	4
NLP/gamma Tubulin	0.011	0.008	-10000	0	-0.079	1	1
microtubule cytoskeleton organization	0.013	0.008	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-10000	0	-10000	0	0
PPP1R12A	0.012	0.001	-10000	0	-10000	0	0
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	0.025	0.029	-10000	0	-0.31	2	2
GRASP65/GM130/RAB1/GTP/PLK1	0.03	0.013	-10000	0	-10000	0	0
RAB1A	0.012	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.016	0.015	-10000	0	-0.17	1	1
mitotic prometaphase	0	0.001	-10000	0	-0.012	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.025	-10000	0	-10000	0	0
microtubule-based process	0.018	0.03	-10000	0	-0.28	3	3
Golgi organization	0.014	0.017	-10000	0	-0.14	3	3
Cohesin/SA2	0.015	0.026	-10000	0	-0.24	3	3
PPP1CB/MYPT1	0.016	0.03	-10000	0	-0.39	2	2
KIF20A	0.009	0.04	-10000	0	-0.54	2	2
APC/C/CDC20	0.017	0.035	-10000	0	-0.33	3	3
PPP2R1A	0.012	0	-10000	0	-10000	0	0
chromosome segregation	0.015	0.024	-10000	0	-0.26	2	2
PRC1	0.012	0	-10000	0	-10000	0	0
ECT2	0.012	0.051	-10000	0	-0.3	9	9
C13orf34	0.016	0.014	-10000	0	-0.16	1	1
NUDC	0.013	0.011	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.015	0.049	-10000	0	-0.38	5	5
spindle assembly	0.014	0.013	-10000	0	-0.11	2	2
spindle stabilization	0.007	0.029	-10000	0	-0.25	2	2
APC/C/HCDH1	0.013	0.036	-10000	0	-0.33	4	4
MKLP2/PLK1	0.018	0.03	-10000	0	-0.28	3	3
CCNB1	0.011	0.029	-10000	0	-0.55	1	1
PPP1CB	0.009	0.04	-10000	0	-0.54	2	2
BTRC	0.012	0	-10000	0	-10000	0	0
ROCK2	0.02	0.012	-10000	0	-10000	0	0
TUBG1	0.013	0.008	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.027	-10000	0	-0.43	1	1
MLF1IP	0.009	0.021	-10000	0	-0.4	1	1
INCENP	0.011	0.029	-10000	0	-0.54	1	1

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.035	0.15	-10000	0	-0.49	35	35
CLTC	0.027	0.004	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.022	0.011	-10000	0	-10000	0	0
Dynamin 2/GTP	0.022	0	-10000	0	-10000	0	0
EXOC4	0.012	0	-10000	0	-10000	0	0
CD59	0.024	0.012	-10000	0	-10000	0	0
CPE	-0.001	0.072	-10000	0	-0.29	21	21
CTNNB1	0.011	0.029	-10000	0	-0.54	1	1
membrane fusion	0.021	0.012	-10000	0	-10000	0	0
CTNND1	0.027	0	-10000	0	-10000	0	0
DNM2	0.012	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.027	0.006	-10000	0	-10000	0	0
TSHR	-0.016	0.086	-10000	0	-0.26	40	40
INS	0.01	0.007	-10000	0	-10000	0	0
BIN1	0.006	0.057	-10000	0	-0.54	4	4
mol:Choline	0.021	0.012	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0.021	0	-10000	0	-10000	0	0
JUP	0.023	0.018	-10000	0	-0.24	1	1
ASAP2/amphiphysin II	0.02	0.036	-10000	0	-0.29	5	5
ARF6/GTP	0.009	0	-10000	0	-10000	0	0
CDH1	0.02	0.031	-10000	0	-0.24	1	1
clathrin-independent pinocytosis	0.009	0	-10000	0	-10000	0	0
MAPK8IP3	0.008	0.047	-10000	0	-0.51	3	3
positive regulation of endocytosis	0.009	0	-10000	0	-10000	0	0
EXOC2	0.012	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.035	0.023	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.012	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.022	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.014	0.029	-10000	0	-0.31	3	3
ACAP1	0.02	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.014	0.031	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.031	0.008	-10000	0	-10000	0	0
JIP4/KLC1	0.024	0	-10000	0	-10000	0	0
EXOC1	0.012	0	-10000	0	-10000	0	0
exocyst	0.035	0.023	-10000	0	-10000	0	0
RALA/GTP	0.009	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.017	0	-10000	0	-10000	0	0
receptor recycling	0.009	0	-10000	0	-10000	0	0
CTNNA1	0.027	0	-10000	0	-10000	0	0
NME1	0.016	0	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.004	-10000	0	-10000	0	0
IL2RA	0.012	0.049	-10000	0	-10000	0	0
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.019	0.058	-10000	0	-10000	0	0
EXOC6	0.012	0	-10000	0	-10000	0	0
PLD1	0.019	0.01	-10000	0	-10000	0	0
PLD2	0.018	0.015	-10000	0	-0.27	1	1
EXOC5	0.006	0.057	-10000	0	-0.54	4	4
PIP5K1C	0.027	0.006	-10000	0	-10000	0	0
SDC1	0.018	0.037	-10000	0	-10000	0	0
ARF6/GDP	0.016	0	-10000	0	-10000	0	0
EXOC7	0.012	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.003	0.022	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.012	-10000	0	-10000	0	0
endocytosis	-0.019	0.036	0.29	5	-10000	0	5
SCAMP2	0.012	0	-10000	0	-10000	0	0
ADRB2	-0.005	0.088	-10000	0	-10000	0	0
EXOC3	0.012	0	-10000	0	-10000	0	0
ASAP2	0.011	0.029	-10000	0	-0.54	1	1
Dynamin 2/GDP	0.023	0	-10000	0	-10000	0	0
KLC1	0.012	0	-10000	0	-10000	0	0
AVPR2	-0.009	0.091	-10000	0	-10000	0	0
RALA	0.012	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.02	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.011	0.029	-9999	-0.54	1	1
SMAD2	0.011	0.016	-9999	-0.24	1	1
SMAD3	0.034	0.016	-9999	-10000	0	0
SMAD3/SMAD4	0.04	0.014	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.024	0.018	-9999	-0.32	1	1
SMAD2/SMAD2/SMAD4	0.034	0.019	-9999	-10000	0	0
PPM1A	0.012	0	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
SMAD2/SMAD4	0.017	0.021	-9999	-0.28	1	1
MAP3K1	0.011	0.029	-9999	-0.54	1	1
TRAP-1/SMAD4	0.011	0.055	-9999	-0.38	7	7
MAPK3	0.011	0.024	-9999	-0.45	1	1
MAPK1	0.011	0.024	-9999	-0.45	1	1
NUP214	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
CTDSP2	0.012	0	-9999	-10000	0	0
CTDSPL	0.011	0.029	-9999	-0.54	1	1
KPNB1	0.012	0	-9999	-10000	0	0
TGFBRAP1	0.003	0.07	-9999	-0.54	6	6
UBE2I	0.012	0	-9999	-10000	0	0
NUP153	0.012	0	-9999	-10000	0	0
KPNA2	0.012	0	-9999	-10000	0	0
PIAS4	0.012	0	-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	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.013	-9999	-10000	0	0
MDM2/SUMO1	0.025	0.028	-9999	-0.29	3	3
HDAC4	0.01	0.034	-9999	-0.45	2	2
Ran/GTP/Exportin 1/HDAC1	0	0.003	-9999	-10000	0	0
SUMO1	0.011	0.029	-9999	-0.54	1	1
NPC/RanGAP1/SUMO1	0.014	0.012	-9999	-0.22	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	0.011	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
SUMO1/HDAC4	0.025	0.026	-9999	-0.35	1	1
SUMO1/HDAC1	0.026	0.019	-9999	-0.35	1	1
RANGAP1	0.012	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.029	0.028	-9999	-0.28	3	3
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.018	0.012	-9999	-0.21	1	1
Ran/GTP	0.023	0.011	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.009	0.04	-9999	-0.54	2	2
UBE2I	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.011	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
PIAS2	0.012	0	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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
coatomer protein complex	-0.001	0.02	-9999	-0.39	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.017	0.009	-9999	-10000	0	0
AP2	0.018	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.017	0.001	-9999	-10000	0	0
CLTB	0.012	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.022	0.001	-9999	-10000	0	0
CD4	-0.004	0.092	-9999	-0.53	11	11
CLTA	0.012	0	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
ARFGAP1	0.009	0.021	-9999	-0.39	1	1
mol:PI-4-5-P2	-0.001	0.014	-9999	-0.18	1	1
ARF1/GTP	-0.001	0.011	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0.018	-9999	-0.33	1	1
mol:Choline	-0.001	0.014	-9999	-0.19	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.012	0	-9999	-10000	0	0
DDEF1	-0.001	0.014	-9999	-0.19	1	1
ARF1/GDP	0.006	0.018	-9999	-0.32	1	1
AP2M1	0.012	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.015	0.001	-9999	-10000	0	0
Rac/GTP	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.022	0.016	-9999	-0.28	1	1
ARFIP2	0.011	0.002	-9999	-10000	0	0
COPA	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.022	0.005	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.009	0.002	-9999	-10000	0	0
GGA3	0.012	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.016	0.007	-9999	-10000	0	0
AP2A1	0.012	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.023	0.011	-9999	-10000	0	0
ARF1/GDP/Membrin	0.016	0.007	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.016	0.001	-9999	-10000	0	0
CYTH2	0.012	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.017	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.009	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	0.024	0.038	-9999	-10000	0	0
PLD2	-0.001	0.014	-9999	-0.19	1	1
ARF-GAP1/v-SNARE	0.009	0.021	-9999	-0.39	1	1
PIP5K1A	-0.001	0.014	-9999	-0.18	1	1
ARF1/GTP/Membrin/GBF1/p115	0.018	0.01	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.014	-9999	-0.19	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0.021	-9999	-0.39	1	1
GOSR2	-0.001	0.006	-9999	-10000	0	0
USO1	-0.001	0.006	-9999	-10000	0	0
GBF1	-0.001	0.006	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.018	0.002	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.015	0.058	-9999	-0.31	11	11

×

Alternative NF-kappaB 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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.018	-9999	-9999
FBXW11	0.012	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.012	-9999	-9999
CHUK	0.012	-9999	-9999
NF kappa B2 p100/RelB	0.037	-9999	-9999
NFKB1	0.012	-9999	-9999
MAP3K14	0.012	-9999	-9999
NF kappa B1 p50/RelB	0.018	-9999	-9999
RELB	0.012	-9999	-9999
NFKB2	0.012	-9999	-9999
NF kappa B2 p52/RelB	0.017	-9999	-9999
regulation of B cell activation	0.017	-9999	-9999

pid_entity	TCGA.FI.A2F9	TCGA.FI.A2F8	TCGA.FI.A2F4	TCGA.FI.A2EX
109_MAP3K5	-0.16	0.046	-0.21	-0.072
47_PPARGC1A	-0.45	0.012	-0.54	0.012
105_BMP4	0.012	0.012	0.012	0.012
105_BMP6	-0.45	0.012	0.012	0.012
105_BMP7	-0.45	-0.45	-0.54	-0.45
105_BMP2	0.012	0.012	0.012	0.012
131_RELN/VLDLR	-0.22	0.032	0.032	-0.22
30_TGFB1/TGF beta receptor Type II	0.012	0.012	0.012	0.012
84_STAT5B	-0.081	0.041	-0.12	-0.099
84_STAT5A	-0.081	0.041	-0.12	-0.099