PARADIGM pathway analysis of mRNASeq expression data - Lung Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	193
Angiopoietin receptor Tie2-mediated signaling	153
FOXM1 transcription factor network	133
Aurora B signaling	125
Signaling events mediated by the Hedgehog family	105
Aurora C signaling	77
Endothelins	73
HIF-1-alpha transcription factor network	69
PLK1 signaling events	65
Visual signal transduction: Cones	63

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
Glypican 2 network	0.3748	193	773	4	-0.2	-0.13	1000	-1000	-0.027	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2971	153	13475	88	-0.62	0.061	1000	-1000	-0.082	-1000
FOXM1 transcription factor network	0.2583	133	6785	51	-0.55	0.01	1000	-1000	-0.18	-1000
Aurora B signaling	0.2427	125	8435	67	-0.4	0.01	1000	-1000	-0.063	-1000
Signaling events mediated by the Hedgehog family	0.2039	105	5471	52	-0.37	0.18	1000	-1000	-0.066	-1000
Aurora C signaling	0.1495	77	544	7	-0.26	0.004	1000	-1000	-0.032	-1000
Endothelins	0.1417	73	7092	96	-0.3	0.025	1000	-1000	-0.076	-1000
HIF-1-alpha transcription factor network	0.1340	69	5312	76	-0.48	0.016	1000	-1000	-0.16	-1000
PLK1 signaling events	0.1262	65	5562	85	-0.29	0.057	1000	-1000	-0.043	-1000
Visual signal transduction: Cones	0.1223	63	2414	38	-0.17	0.01	1000	-1000	-0.054	-1000
Signaling mediated by p38-alpha and p38-beta	0.1223	63	2800	44	-0.12	0.01	1000	-1000	-0.048	-1000
IL4-mediated signaling events	0.1126	58	5283	91	-0.78	0.51	1000	-1000	-0.17	-1000
amb2 Integrin signaling	0.1049	54	4486	82	-0.46	0.01	1000	-1000	-0.066	-1000
Fc-epsilon receptor I signaling in mast cells	0.1029	53	5199	97	-0.15	0.028	1000	-1000	-0.067	-1000
BMP receptor signaling	0.0990	51	4161	81	-0.34	0.027	1000	-1000	-0.076	-1000
TCGA08_retinoblastoma	0.0932	48	387	8	-0.15	0.049	1000	-1000	-0.016	-1000
Signaling events regulated by Ret tyrosine kinase	0.0854	44	3676	82	-0.16	0.01	1000	-1000	-0.079	-1000
Glucocorticoid receptor regulatory network	0.0835	43	4970	114	-0.41	0.24	1000	-1000	-0.062	-1000
TCGA08_p53	0.0835	43	305	7	-0.1	0.052	1000	-1000	-0.02	-1000
Osteopontin-mediated events	0.0796	41	1576	38	-0.35	0.011	1000	-1000	-0.09	-1000
FOXA2 and FOXA3 transcription factor networks	0.0796	41	1886	46	-0.5	0.015	1000	-1000	-0.14	-1000
Visual signal transduction: Rods	0.0796	41	2132	52	-0.15	0.01	1000	-1000	-0.074	-1000
Arf6 signaling events	0.0757	39	2423	62	-0.19	0.012	1000	-1000	-0.056	-1000
LPA4-mediated signaling events	0.0738	38	457	12	-0.12	0.012	1000	-1000	-0.024	-1000
Canonical Wnt signaling pathway	0.0718	37	1910	51	-0.34	0.15	1000	-1000	-0.046	-1000
Thromboxane A2 receptor signaling	0.0699	36	3859	105	-0.09	0.028	1000	-1000	-0.059	-1000
Glypican 1 network	0.0699	36	1749	48	-0.12	0.017	1000	-1000	-0.041	-1000
Syndecan-1-mediated signaling events	0.0660	34	1173	34	-0.33	0.01	1000	-1000	-0.05	-1000
Effects of Botulinum toxin	0.0660	34	901	26	-0.089	0.01	1000	-1000	-0.052	-1000
Integrins in angiogenesis	0.0641	33	2833	84	-0.35	0.024	1000	-1000	-0.072	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0641	33	4036	120	-0.26	0.2	1000	-1000	-0.064	-1000
Presenilin action in Notch and Wnt signaling	0.0621	32	2008	61	-0.34	0.02	1000	-1000	-0.053	-1000
p75(NTR)-mediated signaling	0.0621	32	4019	125	-0.3	0.018	1000	-1000	-0.088	-1000
Ephrin B reverse signaling	0.0621	32	1575	48	-0.095	0.054	1000	-1000	-0.061	-1000
IL23-mediated signaling events	0.0621	32	1967	60	-0.28	0.015	1000	-1000	-0.15	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0583	30	2040	68	-0.15	0.036	1000	-1000	-0.12	-1000
ErbB4 signaling events	0.0563	29	2057	69	-0.19	0.21	1000	-1000	-0.08	-1000
Aurora A signaling	0.0544	28	1710	60	-0.29	0.015	1000	-1000	-0.056	-1000
IL6-mediated signaling events	0.0544	28	2158	75	-0.33	0.041	1000	-1000	-0.092	-1000
EGFR-dependent Endothelin signaling events	0.0485	25	539	21	-0.09	0.01	1000	-1000	-0.059	-1000
PDGFR-alpha signaling pathway	0.0447	23	1029	44	-0.31	0.027	1000	-1000	-0.053	-1000
Reelin signaling pathway	0.0427	22	1277	56	-0.096	0.01	1000	-1000	-0.061	-1000
Syndecan-3-mediated signaling events	0.0427	22	777	35	-0.21	0.01	1000	-1000	-0.056	-1000
Class IB PI3K non-lipid kinase events	0.0427	22	66	3	-0.012	-1000	1000	-1000	-0.015	-1000
Nongenotropic Androgen signaling	0.0408	21	1143	52	-0.062	0.01	1000	-1000	-0.048	-1000
Wnt signaling	0.0408	21	150	7	-0.057	0.009	1000	-1000	-0.029	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0408	21	710	33	-0.14	0.024	1000	-1000	-0.055	-1000
Regulation of Androgen receptor activity	0.0388	20	1430	70	-0.26	0.026	1000	-1000	-0.063	-1000
Syndecan-2-mediated signaling events	0.0369	19	1316	69	-0.097	0.031	1000	-1000	-0.048	-1000
Nectin adhesion pathway	0.0369	19	1199	63	-0.045	0.01	1000	-1000	-0.061	-1000
HIF-2-alpha transcription factor network	0.0369	19	856	43	-0.12	0.046	1000	-1000	-0.085	-1000
Coregulation of Androgen receptor activity	0.0350	18	1389	76	-0.14	0.018	1000	-1000	-0.046	-1000
PLK2 and PLK4 events	0.0350	18	56	3	-0.017	-0.003	1000	-1000	-0.022	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0350	18	938	52	-0.25	0.042	1000	-1000	-0.054	-1000
Syndecan-4-mediated signaling events	0.0350	18	1248	67	-0.16	0.016	1000	-1000	-0.079	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0291	15	535	34	-0.041	0.01	1000	-1000	-0.054	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0291	15	1876	125	-0.31	0.034	1000	-1000	-0.08	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0291	15	1222	78	-0.042	0.036	1000	-1000	-0.068	-1000
IL12-mediated signaling events	0.0272	14	1287	87	-0.095	0.039	1000	-1000	-0.12	-1000
Noncanonical Wnt signaling pathway	0.0272	14	383	26	-0.057	0.01	1000	-1000	-0.071	-1000
FAS signaling pathway (CD95)	0.0272	14	678	47	-0.25	0.011	1000	-1000	-0.047	-1000
LPA receptor mediated events	0.0272	14	1483	102	-0.12	0.03	1000	-1000	-0.071	-1000
BCR signaling pathway	0.0272	14	1394	99	-0.14	0.025	1000	-1000	-0.076	-1000
Caspase cascade in apoptosis	0.0252	13	992	74	-0.038	0.031	1000	-1000	-0.047	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0252	13	731	54	-0.13	0.021	1000	-1000	-0.085	-1000
Signaling events mediated by PTP1B	0.0252	13	1033	76	-0.092	0.016	1000	-1000	-0.073	-1000
Signaling events mediated by HDAC Class III	0.0252	13	546	40	-0.12	0.018	1000	-1000	-0.04	-1000
S1P1 pathway	0.0252	13	477	36	-0.058	0.012	1000	-1000	-0.049	-1000
Signaling events mediated by PRL	0.0252	13	443	34	-0.18	0.022	1000	-1000	-0.035	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0233	12	1074	85	-0.045	0.029	1000	-1000	-0.067	-1000
TCR signaling in naïve CD8+ T cells	0.0233	12	1122	93	-0.072	0.041	1000	-1000	-0.07	-1000
Ephrin A reverse signaling	0.0214	11	82	7	-0.01	0.008	1000	-1000	-0.027	-1000
IL1-mediated signaling events	0.0214	11	740	62	-0.15	0.048	1000	-1000	-0.084	-1000
S1P5 pathway	0.0214	11	200	17	-0.031	0.029	1000	-1000	-0.048	-1000
EPHB forward signaling	0.0214	11	1002	85	-0.066	0.049	1000	-1000	-0.081	-1000
Regulation of p38-alpha and p38-beta	0.0214	11	605	54	-0.08	0.017	1000	-1000	-0.052	-1000
Calcium signaling in the CD4+ TCR pathway	0.0214	11	351	31	-0.1	0.012	1000	-1000	-0.083	-1000
ErbB2/ErbB3 signaling events	0.0194	10	712	65	-0.1	0.02	1000	-1000	-0.057	-1000
BARD1 signaling events	0.0194	10	593	57	-0.18	0.03	1000	-1000	-0.053	-1000
IL2 signaling events mediated by STAT5	0.0175	9	206	22	-0.11	0.054	1000	-1000	-0.05	-1000
S1P4 pathway	0.0175	9	232	25	-0.031	0.011	1000	-1000	-0.047	-1000
Regulation of nuclear SMAD2/3 signaling	0.0155	8	1126	136	-0.1	0.054	1000	-1000	-0.069	-1000
IL27-mediated signaling events	0.0155	8	428	51	-0.11	0.011	1000	-1000	-0.054	-1000
Plasma membrane estrogen receptor signaling	0.0155	8	745	86	-0.036	0.03	1000	-1000	-0.076	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0136	7	196	28	-0.031	0.021	1000	-1000	-0.045	-1000
Signaling mediated by p38-gamma and p38-delta	0.0136	7	113	15	0	0.022	1000	-1000	-0.023	-1000
Regulation of Telomerase	0.0136	7	736	102	-0.092	0.03	1000	-1000	-0.1	-1000
Ras signaling in the CD4+ TCR pathway	0.0136	7	133	17	-0.014	0.023	1000	-1000	-0.04	-1000
JNK signaling in the CD4+ TCR pathway	0.0117	6	108	17	-0.013	0.031	1000	-1000	-0.052	-1000
Cellular roles of Anthrax toxin	0.0117	6	235	39	-0.046	0.015	1000	-1000	-0.03	-1000
Hedgehog signaling events mediated by Gli proteins	0.0117	6	435	65	-0.18	0.053	1000	-1000	-0.06	-1000
Retinoic acid receptors-mediated signaling	0.0117	6	378	58	-0.17	0.031	1000	-1000	-0.055	-1000
Arf6 trafficking events	0.0117	6	475	71	-0.081	0.034	1000	-1000	-0.066	-1000
Insulin Pathway	0.0117	6	499	74	-0.15	0.029	1000	-1000	-0.076	-1000
VEGFR1 specific signals	0.0117	6	388	56	-0.31	0.043	1000	-1000	-0.067	-1000
p38 MAPK signaling pathway	0.0117	6	307	44	-0.08	0.026	1000	-1000	-0.057	-1000
Signaling events mediated by HDAC Class II	0.0097	5	408	75	-0.044	0.027	1000	-1000	-0.052	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0097	5	457	83	-0.063	0.039	1000	-1000	-0.071	-1000
FoxO family signaling	0.0097	5	338	64	-0.12	0.055	1000	-1000	-0.079	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0097	5	410	74	-0.11	0.059	1000	-1000	-0.078	-1000
Class I PI3K signaling events	0.0097	5	405	73	-0.08	0.022	1000	-1000	-0.062	-1000
IFN-gamma pathway	0.0078	4	339	68	-0.08	0.046	1000	-1000	-0.086	-1000
Ceramide signaling pathway	0.0078	4	371	76	-0.09	0.036	1000	-1000	-0.053	-1000
Signaling events mediated by HDAC Class I	0.0078	4	517	104	-0.049	0.043	1000	-1000	-0.054	-1000
IL2 signaling events mediated by PI3K	0.0078	4	281	58	-0.15	0.065	1000	-1000	-0.077	-1000
TCGA08_rtk_signaling	0.0078	4	108	26	-0.024	0.036	1000	-1000	-0.02	-1000
Circadian rhythm pathway	0.0058	3	78	22	-0.026	0.034	1000	-1000	-0.068	-1000
Arf6 downstream pathway	0.0058	3	168	43	-0.036	0.025	1000	-1000	-0.038	-1000
IGF1 pathway	0.0058	3	221	57	-0.037	0.04	1000	-1000	-0.081	-1000
S1P3 pathway	0.0058	3	156	42	-0.03	0.021	1000	-1000	-0.055	-1000
Rapid glucocorticoid signaling	0.0058	3	63	20	-0.007	0.01	1000	-1000	-0.038	-1000
TRAIL signaling pathway	0.0039	2	128	48	-0.009	0.039	1000	-1000	-0.06	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0039	2	116	45	-0.011	0.06	1000	-1000	-0.081	-1000
E-cadherin signaling in the nascent adherens junction	0.0039	2	183	76	-0.037	0.049	1000	-1000	-0.073	-1000
PDGFR-beta signaling pathway	0.0039	2	237	97	-0.036	0.048	1000	-1000	-0.07	-1000
Canonical NF-kappaB pathway	0.0019	1	44	39	-0.013	0.066	1000	-1000	-0.068	-1000
a4b1 and a4b7 Integrin signaling	0.0019	1	8	5	-0.002	0.009	1000	-1000	-0.038	-1000
EPO signaling pathway	0.0019	1	90	55	-0.005	0.058	1000	-1000	-0.073	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0019	1	39	37	-0.005	0.037	1000	-1000	-0.055	-1000
ceramide signaling pathway	0.0019	1	56	49	-0.011	0.039	1000	-1000	-0.045	-1000
E-cadherin signaling events	0.0019	1	8	5	-0.002	0.01	1000	-1000	-0.039	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	12	23	-0.003	0.036	1000	-1000	-0.061	-1000
Insulin-mediated glucose transport	0.0000	0	25	32	-0.003	0.034	1000	-1000	-0.054	-1000
mTOR signaling pathway	0.0000	0	13	53	-0.001	0.026	1000	-1000	-0.052	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	25	68	-0.033	0.045	1000	-1000	-0.054	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	19	36	-0.003	0.018	1000	-1000	-0.059	-1000
Atypical NF-kappaB pathway	0.0000	0	12	31	-0.002	0.038	1000	-1000	-0.051	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	11	27	-0.001	0.023	1000	-1000	-0.046	-1000
E-cadherin signaling in keratinocytes	0.0000	0	27	43	-0.007	0.037	1000	-1000	-0.06	-1000
Arf1 pathway	0.0000	0	20	54	-0.006	0.024	1000	-1000	-0.041	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.01	1000	-1000	-0.046	-1000
Total	NA	3020	175416	7203	-18	-1000	131000	-131000	-8.2	-131000

Glypican 2 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.15	0.24	-9999	-0.51	157	157
GPC2	-0.13	0.23	-9999	-0.51	136	136
GPC2/Midkine	-0.2	0.23	-9999	-0.43	240	240
neuron projection morphogenesis	-0.2	0.23	-9999	-0.43	240	240

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.43	0.52	-10000	0	-0.95	248	248
NCK1/PAK1/Dok-R	-0.21	0.22	-10000	0	-0.44	248	248
NCK1/Dok-R	-0.56	0.61	-10000	0	-1.2	248	248
PIK3CA	0.011	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.061	0.1	0.24	128	-10000	0	128
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.003	0.033	-10000	0	-0.51	2	2
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.012	0.2	0.25	124	-0.51	53	177
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.5	0.55	-10000	0	-1	248	248
FN1	0.005	0.05	-10000	0	-0.5	5	5
PLD2	-0.54	0.67	-10000	0	-1.2	248	248
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.025	0.13	-10000	0	-0.51	35	35
ELK1	-0.47	0.58	-10000	0	-1	248	248
GRB7	0.004	0.055	-10000	0	-0.5	6	6
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.53	0.59	-10000	0	-1.1	248	248
CDKN1A	-0.29	0.35	-10000	0	-0.65	245	245
ITGA5	0.008	0.032	-10000	0	-0.5	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.56	0.61	-10000	0	-1.2	248	248
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.3	0.38	-10000	0	-0.68	248	248
PLG	-0.55	0.67	-10000	0	-1.2	248	248
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.41	0.48	-10000	0	-0.9	248	248
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.005	0.023	-10000	0	-0.5	1	1
ANGPT2	-0.22	0.3	-10000	0	-0.63	154	154
BMX	-0.62	0.7	-10000	0	-1.3	248	248
ANGPT1	-0.32	0.55	-10000	0	-1.3	128	128
tube development	-0.33	0.4	-10000	0	-0.74	246	246
ANGPT4	-0.26	0.25	-10000	0	-0.5	264	264
response to hypoxia	-0.03	0.035	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.58	0.7	-10000	0	-1.3	248	248
alpha5/beta1 Integrin	-0.001	0.022	-10000	0	-0.36	2	2
FGF2	-0.065	0.18	-10000	0	-0.5	74	74
STAT5A (dimer)	-0.38	0.46	-10000	0	-0.85	246	246
mol:L-citrulline	-0.3	0.38	-10000	0	-0.68	248	248
AGTR1	-0.16	0.24	-10000	0	-0.5	167	167
MAPK14	-0.57	0.68	-10000	0	-1.2	248	248
Tie2/SHP2	-0.49	0.55	-10000	0	-1.1	218	218
TEK	-0.53	0.62	-10000	0	-1.2	218	218
RPS6KB1	-0.41	0.5	-10000	0	-0.91	248	248
Angiotensin II/AT1	-0.11	0.17	-10000	0	-0.36	167	167
Tie2/Ang1/GRB2	-0.57	0.7	-10000	0	-1.2	248	248
MAPK3	-0.48	0.6	-10000	0	-1.1	248	248
MAPK1	-0.48	0.6	-10000	0	-1.1	248	248
Tie2/Ang1/GRB7	-0.57	0.7	-10000	0	-1.2	248	248
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.54	0.67	-10000	0	-1.2	248	248
PI3K	-0.51	0.61	-10000	0	-1.1	248	248
FES	-0.57	0.67	-10000	0	-1.2	248	248
Crk/Dok-R	-0.56	0.61	-10000	0	-1.2	248	248
Tie2/Ang1/ABIN2	-0.57	0.7	-10000	0	-1.2	248	248
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.37	0.46	-10000	0	-0.84	248	248
STAT5A	0.009	0.022	-10000	0	-0.5	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.41	0.5	-10000	0	-0.91	248	248
Tie2/Ang2	-0.49	0.57	-10000	0	-1.1	246	246
Tie2/Ang1	-0.61	0.76	-10000	0	-1.3	248	248
FOXO1	-0.38	0.46	-10000	0	-0.84	248	248
ELF1	-0.029	0.051	-10000	0	-10000	0	0
ELF2	-0.55	0.68	-10000	0	-1.2	248	248
mol:Choline	-0.51	0.62	-10000	0	-1.1	248	248
cell migration	-0.12	0.12	-10000	0	-0.24	248	248
FYN	-0.39	0.46	-10000	0	-0.86	246	246
DOK2	-0.033	0.14	-10000	0	-0.5	43	43
negative regulation of cell cycle	-0.26	0.32	-10000	0	-0.59	245	245
ETS1	-0.049	0.1	-10000	0	-0.53	1	1
PXN	-0.32	0.4	-10000	0	-0.73	248	248
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.35	0.43	-10000	0	-0.79	248	248
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.067	0.14	-10000	0	-0.39	40	40
MAPKKK cascade	-0.51	0.62	-10000	0	-1.1	248	248
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.58	0.69	-10000	0	-1.2	248	248
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.26	0.34	-10000	0	-0.6	248	248
mol:Phosphatidic acid	-0.51	0.62	-10000	0	-1.1	248	248
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.3	0.38	-10000	0	-0.68	248	248
Rac1/GTP	-0.41	0.42	-10000	0	-0.84	248	248
MMP2	-0.55	0.67	-10000	0	-1.2	248	248

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.42	0.53	-9999	-1	167	167
PLK1	-0.15	0.19	-9999	-0.36	158	158
BIRC5	-0.19	0.2	-9999	-10000	0	0
HSPA1B	-0.42	0.53	-9999	-1	167	167
MAP2K1	-0.002	0.034	-9999	-10000	0	0
BRCA2	-0.42	0.53	-9999	-1	165	165
FOXM1	-0.54	0.68	-9999	-1.3	189	189
XRCC1	-0.42	0.53	-9999	-1	167	167
FOXM1B/p19	-0.5	0.48	-9999	-1	185	185
Cyclin D1/CDK4	-0.43	0.5	-9999	-0.98	169	169
CDC2	-0.45	0.56	-9999	-1.1	189	189
TGFA	-0.42	0.49	-9999	-0.94	175	175
SKP2	-0.43	0.53	-9999	-1	166	166
CCNE1	-0.19	0.26	-9999	-0.52	190	190
CKS1B	-0.43	0.54	-9999	-1	160	160
RB1	-0.22	0.18	-9999	-0.45	79	79
FOXM1C/SP1	-0.48	0.6	-9999	-1.1	183	183
AURKB	-0.17	0.2	-9999	-10000	0	0
CENPF	-0.48	0.58	-9999	-1.1	188	188
CDK4	0.001	0.053	-9999	-0.53	5	5
MYC	-0.37	0.47	-9999	-0.89	166	166
CHEK2	-0.007	0.064	-9999	-0.56	5	5
ONECUT1	-0.47	0.54	-9999	-1	186	186
CDKN2A	-0.14	0.23	-9999	-0.5	152	152
LAMA4	-0.43	0.54	-9999	-1	178	178
FOXM1B/HNF6	-0.55	0.63	-9999	-1.2	189	189
FOS	-0.44	0.56	-9999	-1.1	169	169
SP1	0.01	0.001	-9999	-10000	0	0
CDC25B	-0.42	0.53	-9999	-1	173	173
response to radiation	-0.013	0.031	-9999	-10000	0	0
CENPB	-0.42	0.53	-9999	-1	173	173
CENPA	-0.5	0.59	-9999	-1.1	207	207
NEK2	-0.5	0.58	-9999	-1.1	206	206
HIST1H2BA	-0.43	0.53	-9999	-1	162	162
CCNA2	-0.12	0.22	-9999	-0.52	119	119
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	-0.5	0.62	-9999	-1.2	175	175
CCNB2	-0.49	0.58	-9999	-1.1	199	199
CCNB1	-0.47	0.58	-9999	-1.1	177	177
ETV5	-0.43	0.54	-9999	-1	163	163
ESR1	-0.44	0.54	-9999	-1	169	169
CCND1	-0.44	0.51	-9999	-1	172	172
GSK3A	0.002	0.027	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.18	0.25	-9999	-0.44	220	220
CDK2	0.006	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.016	0.037	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.53	0.49	-9999	-1.1	200	200
GAS1	-0.44	0.54	-9999	-1.1	165	165
MMP2	-0.42	0.53	-9999	-1	173	173
RB1/FOXM1C	-0.46	0.54	-9999	-1.1	185	185
CREBBP	0.01	0	-9999	-10000	0	0

×

Aurora B signaling

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
Condensin I complex	-0.14	0.16	-9999	-0.32	212	212
STMN1	-0.18	0.19	-9999	-0.36	267	267
Aurora B/RasGAP/Survivin	-0.3	0.26	-9999	-0.5	320	320
Chromosomal passenger complex/Cul3 protein complex	-0.13	0.14	-9999	-0.29	165	165
BIRC5	-0.29	0.26	-9999	-0.52	297	297
DES	-0.38	0.37	-9999	-0.74	260	260
Aurora C/Aurora B/INCENP	-0.14	0.14	-9999	-0.27	271	271
Aurora B/TACC1	-0.16	0.17	-9999	-0.31	274	274
Aurora B/PP2A	-0.18	0.18	-9999	-0.35	267	267
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.032	0.044	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.33	0.31	-9999	-0.58	301	301
Cul3 protein complex	-0.015	0.067	-9999	-0.3	26	26
KIF2C	-0.12	0.11	-9999	-0.22	240	240
PEBP1	0.004	0.005	-9999	-10000	0	0
KIF20A	-0.27	0.26	-9999	-0.51	277	277
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.18	0.18	-9999	-0.35	267	267
SEPT1	0.009	0.022	-9999	-0.5	1	1
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.059	0.072	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.003	-9999	-10000	0	0
H3F3B	-0.086	0.097	-9999	-0.18	267	267
AURKB	-0.26	0.26	-9999	-0.51	267	267
AURKC	0.004	0.055	-9999	-0.5	6	6
CDCA8	-0.17	0.25	-9999	-0.52	170	170
cytokinesis	-0.22	0.2	-9999	-0.43	213	213
Aurora B/Septin1	-0.2	0.2	-9999	-0.43	190	190
AURKA	-0.091	0.21	-9999	-0.51	100	100
INCENP	0.003	0.007	-9999	-10000	0	0
KLHL13	-0.014	0.11	-9999	-0.5	24	24
BUB1	-0.13	0.23	-9999	-0.51	133	133
hSgo1/Aurora B/Survivin	-0.4	0.35	-9999	-0.64	327	327
EVI5	0.009	0.002	-9999	-10000	0	0
RhoA/GTP	-0.21	0.22	-9999	-0.46	180	180
SGOL1	-0.23	0.26	-9999	-0.51	237	237
CENPA	-0.16	0.15	-9999	-0.3	258	258
NCAPG	-0.2	0.26	-9999	-0.51	213	213
Aurora B/HC8 Proteasome	-0.18	0.18	-9999	-0.35	267	267
NCAPD2	0.009	0.023	-9999	-0.51	1	1
Aurora B/PP1-gamma	-0.18	0.18	-9999	-0.35	267	267
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.21	0.26	-9999	-0.51	223	223
NPM1	-0.081	0.079	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.007	0.039	-9999	-0.5	3	3
mitotic prometaphase	-0.008	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.18	-9999	-0.35	267	267
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.23	0.24	-9999	-0.48	204	204
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.081	0.079	-9999	-10000	0	0
MYLK	-0.098	0.12	-9999	-0.2	260	260
KIF23	-0.1	0.21	-9999	-0.52	108	108
VIM	-0.18	0.19	-9999	-0.36	267	267
RACGAP1	0	0.052	-9999	-0.52	5	5
mitosis	0	0	-9999	-10000	0	0
NCL	-0.081	0.079	-9999	-10000	0	0
Chromosomal passenger complex	-0.19	0.19	-9999	-0.36	254	254
Chromosomal passenger complex/EVI5	-0.32	0.31	-9999	-0.62	256	256
TACC1	-0.013	0.1	-9999	-0.5	23	23
PPP2R5D	0.01	0	-9999	-10000	0	0
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.21	0.25	-10000	0	-0.66	91	91
IHH	-0.31	0.27	-10000	0	-0.54	296	296
SHH Np/Cholesterol/GAS1	-0.043	0.1	-10000	0	-0.28	77	77
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.042	0.1	0.28	77	-10000	0	77
SMO/beta Arrestin2	-0.21	0.22	-10000	0	-0.51	106	106
SMO	-0.23	0.23	-10000	0	-0.53	112	112
AKT1	-0.095	0.11	-10000	0	-0.35	10	10
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.008	0.032	-10000	0	-0.5	2	2
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.23	0.23	-10000	0	-0.52	112	112
STIL	-0.2	0.22	-10000	0	-0.51	125	125
DHH N/PTCH2	-0.026	0.092	-10000	0	-0.35	38	38
DHH N/PTCH1	-0.19	0.2	-10000	0	-0.5	97	97
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.027	0.13	-10000	0	-0.5	37	37
PTHLH	-0.28	0.29	-10000	0	-0.77	91	91
determination of left/right symmetry	-0.23	0.23	-10000	0	-0.52	112	112
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
skeletal system development	-0.28	0.29	-10000	0	-0.76	91	91
IHH N/Hhip	-0.37	0.26	-10000	0	-0.5	386	386
DHH N/Hhip	-0.22	0.2	-10000	0	-0.38	293	293
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.23	0.23	-10000	0	-0.52	112	112
pancreas development	-0.27	0.25	-10000	0	-0.5	280	280
HHAT	0.008	0.032	-10000	0	-0.5	2	2
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.005	0.086	-10000	0	-0.5	15	15
somite specification	-0.23	0.23	-10000	0	-0.52	112	112
SHH Np/Cholesterol/PTCH1	-0.18	0.2	-10000	0	-0.47	115	115
SHH Np/Cholesterol/PTCH2	-0.035	0.09	-10000	0	-0.26	69	69
SHH Np/Cholesterol/Megalin	-0.11	0.15	-10000	0	-0.3	190	190
SHH	-0.032	0.13	-10000	0	-0.35	68	68
catabolic process	-0.2	0.2	-10000	0	-0.53	81	81
SMO/Vitamin D3	-0.2	0.22	-10000	0	-0.52	115	115
SHH Np/Cholesterol/Hhip	-0.18	0.17	-10000	0	-0.3	302	302
LRP2	-0.13	0.23	-10000	0	-0.5	144	144
receptor-mediated endocytosis	-0.26	0.23	-10000	0	-0.52	181	181
SHH Np/Cholesterol/BOC	-0.036	0.09	-10000	0	-0.26	70	70
SHH Np/Cholesterol/CDO	-0.042	0.1	-10000	0	-0.28	76	76
mesenchymal cell differentiation	0.18	0.16	0.3	302	-10000	0	302
mol:Vitamin D3	-0.18	0.2	-10000	0	-0.47	117	117
IHH N/PTCH2	-0.18	0.16	-10000	0	-0.32	296	296
CDON	-0.004	0.083	-10000	0	-0.5	14	14
IHH N/PTCH1	-0.2	0.21	-10000	0	-0.54	81	81
Megalin/LRPAP1	-0.099	0.16	-10000	0	-0.35	144	144
PTCH2	0.009	0.022	-10000	0	-0.5	1	1
SHH Np/Cholesterol	-0.036	0.092	-10000	0	-0.27	68	68
PTCH1	-0.2	0.2	-10000	0	-0.53	81	81
HHIP	-0.27	0.25	-10000	0	-0.5	280	280

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.14	0.14	-9999	-0.27	271	271
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.041	0.039	-9999	-10000	0	0
AURKB	-0.26	0.26	-9999	-0.51	267	267
AURKC	0.004	0.055	-9999	-0.5	6	6

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.048	0.2	0.26	1	-0.45	64	65
PTK2B	0.008	0.032	-10000	0	-0.5	2	2
mol:Ca2+	-0.053	0.28	-10000	0	-0.95	42	42
EDN1	-0.066	0.23	-10000	0	-0.54	82	82
EDN3	-0.14	0.22	-10000	0	-0.5	142	142
EDN2	-0.14	0.23	-10000	0	-0.51	147	147
HRAS/GDP	-0.079	0.2	-10000	0	-0.47	68	68
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.005	0.13	-10000	0	-0.39	29	29
ADCY4	-0.065	0.17	-10000	0	-0.49	44	44
ADCY5	-0.088	0.2	-10000	0	-0.52	63	63
ADCY6	-0.054	0.16	-10000	0	-0.46	44	44
ADCY7	-0.055	0.16	-10000	0	-0.48	40	40
ADCY1	-0.059	0.16	-10000	0	-0.47	44	44
ADCY2	-0.083	0.19	-10000	0	-0.51	53	53
ADCY3	-0.054	0.16	-10000	0	-0.47	39	39
ADCY8	-0.16	0.19	-10000	0	-0.45	101	101
ADCY9	-0.059	0.16	-10000	0	-0.49	40	40
arachidonic acid secretion	-0.065	0.2	-10000	0	-0.5	62	62
ETB receptor/Endothelin-1/Gq/GTP	-0.16	0.2	-10000	0	-0.36	171	171
GNAO1	0.003	0.06	-10000	0	-0.51	7	7
HRAS	0.009	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.025	0.22	0.23	184	-0.42	64	248
ETA receptor/Endothelin-1/Gs/GTP	0.015	0.22	0.21	179	-0.47	47	226
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.097	0.26	-10000	0	-0.48	124	124
EDNRB	-0.28	0.25	-10000	0	-0.5	296	296
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.057	0.22	-10000	0	-0.6	45	45
CYSLTR1	-0.063	0.23	-10000	0	-0.64	47	47
SLC9A1	-0.022	0.11	0.18	1	-0.3	32	33
mol:GDP	-0.091	0.21	-10000	0	-0.5	72	72
SLC9A3	-0.3	0.36	-10000	0	-0.61	229	229
RAF1	-0.087	0.2	-10000	0	-0.52	62	62
JUN	-0.019	0.19	-10000	0	-0.65	28	28
JAK2	-0.05	0.2	0.26	1	-0.46	65	66
mol:IP3	-0.089	0.18	-10000	0	-0.4	83	83
ETA receptor/Endothelin-1	-0.021	0.28	0.26	184	-0.51	73	257
PLCB1	0.007	0.032	-10000	0	-0.5	2	2
PLCB2	0	0.071	-10000	0	-0.5	10	10
ETA receptor/Endothelin-3	-0.095	0.18	-10000	0	-0.37	144	144
FOS	-0.078	0.24	-10000	0	-0.88	32	32
Gai/GDP	-0.008	0.082	-10000	0	-0.58	3	3
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.25	-10000	0	-0.56	103	103
BCAR1	0.009	0.022	-10000	0	-0.5	1	1
PRKCB1	-0.085	0.17	-10000	0	-0.4	75	75
GNAQ	0.01	0.023	-10000	0	-0.5	1	1
GNAZ	-0.031	0.14	-10000	0	-0.5	41	41
GNAL	-0.002	0.077	-10000	0	-0.5	12	12
Gs family/GDP	-0.11	0.17	-10000	0	-0.45	75	75
ETA receptor/Endothelin-1/Gq/GTP	-0.009	0.14	-10000	0	-0.35	47	47
MAPK14	-0.12	0.18	-10000	0	-0.41	87	87
TRPC6	-0.06	0.31	-10000	0	-1	41	41
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.19	-10000	0	-0.4	112	112
ETB receptor/Endothelin-2	-0.3	0.23	-10000	0	-0.43	350	350
ETB receptor/Endothelin-3	-0.29	0.22	-10000	0	-0.43	353	353
ETB receptor/Endothelin-1	-0.25	0.26	-10000	0	-0.44	304	304
MAPK3	-0.085	0.24	-10000	0	-0.79	39	39
MAPK1	-0.085	0.24	-10000	0	-0.79	39	39
Rac1/GDP	-0.079	0.2	-10000	0	-0.47	68	68
cAMP biosynthetic process	-0.1	0.19	-10000	0	-0.49	65	65
MAPK8	-0.03	0.21	-10000	0	-0.6	44	44
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.15	0.18	-10000	0	-0.4	121	121
p130Cas/CRK/Src/PYK2	-0.09	0.23	-10000	0	-0.59	64	64
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.079	0.2	-10000	0	-0.47	67	67
COL1A2	-0.2	0.28	-10000	0	-0.62	116	116
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.099	0.18	-10000	0	-0.38	149	149
mol:DAG	-0.089	0.18	-10000	0	-0.4	83	83
MAP2K2	-0.081	0.21	-10000	0	-0.62	48	48
MAP2K1	-0.081	0.21	-10000	0	-0.62	48	48
EDNRA	0.011	0.1	0.2	1	-0.37	9	10
positive regulation of muscle contraction	-0.035	0.17	0.23	1	-0.46	40	41
Gq family/GDP	-0.076	0.17	-10000	0	-0.52	40	40
HRAS/GTP	-0.094	0.2	-10000	0	-0.47	69	69
PRKCH	-0.079	0.17	-10000	0	-0.46	50	50
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.08	0.17	-10000	0	-0.46	51	51
PRKCB	-0.086	0.19	-10000	0	-0.49	54	54
PRKCE	-0.082	0.18	-10000	0	-0.47	52	52
PRKCD	-0.08	0.17	-10000	0	-0.46	49	49
PRKCG	-0.11	0.19	-10000	0	-0.46	78	78
regulation of vascular smooth muscle contraction	-0.092	0.28	-10000	0	-1	32	32
PRKCQ	-0.12	0.21	-10000	0	-0.44	105	105
PLA2G4A	-0.072	0.22	-10000	0	-0.55	62	62
GNA14	-0.003	0.084	-10000	0	-0.51	14	14
GNA15	0.01	0.004	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.032	-10000	0	-0.5	2	2
Rac1/GTP	0.025	0.22	0.23	184	-0.42	64	248
MMP1	-0.22	0.2	-10000	0	-0.37	288	288

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.33	0.46	-9999	-1.1	96	96
HDAC7	0.008	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.27	0.36	-9999	-0.82	97	97
SMAD4	0.011	0.003	-9999	-10000	0	0
ID2	-0.33	0.46	-9999	-1.1	96	96
AP1	-0.023	0.085	-9999	-0.36	30	30
ABCG2	-0.35	0.49	-9999	-1.1	103	103
HIF1A	-0.04	0.071	-9999	-10000	0	0
TFF3	-0.38	0.51	-9999	-1.1	119	119
GATA2	-0.033	0.14	-9999	-0.51	41	41
AKT1	-0.045	0.08	-9999	-10000	0	0
response to hypoxia	-0.062	0.083	-9999	-0.24	8	8
MCL1	-0.33	0.46	-9999	-1.1	96	96
NDRG1	-0.33	0.46	-9999	-1.1	96	96
SERPINE1	-0.33	0.47	-9999	-1.1	98	98
FECH	-0.33	0.46	-9999	-1.1	95	95
FURIN	-0.33	0.47	-9999	-1.1	97	97
NCOA2	0.006	0.05	-9999	-0.5	5	5
EP300	-0.045	0.11	-9999	-0.33	13	13
HMOX1	-0.33	0.46	-9999	-1.1	96	96
BHLHE40	-0.33	0.46	-9999	-1.1	96	96
BHLHE41	-0.33	0.47	-9999	-1.1	97	97
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.038	0.07	-9999	-0.41	3	3
ENG	-0.011	0.1	-9999	-0.58	6	6
JUN	0.005	0.039	-9999	-0.5	3	3
RORA	-0.33	0.47	-9999	-1.1	98	98
ABCB1	-0.12	0.25	-9999	-1.2	23	23
TFRC	-0.33	0.46	-9999	-1.1	93	93
CXCR4	-0.33	0.46	-9999	-1.1	96	96
TF	-0.38	0.51	-9999	-1.1	123	123
CITED2	-0.33	0.46	-9999	-1.1	93	93
HIF1A/ARNT	-0.37	0.55	-9999	-1.2	110	110
LDHA	-0.045	0.058	-9999	-10000	0	0
ETS1	-0.33	0.46	-9999	-1.1	96	96
PGK1	-0.33	0.46	-9999	-1.1	96	96
NOS2	-0.35	0.49	-9999	-1.1	114	114
ITGB2	-0.33	0.47	-9999	-1.1	97	97
ALDOA	-0.33	0.46	-9999	-1.1	95	95
Cbp/p300/CITED2	-0.32	0.48	-9999	-1.1	91	91
FOS	-0.019	0.12	-9999	-0.51	27	27
HK2	-0.33	0.46	-9999	-1.1	99	99
SP1	0.015	0.014	-9999	-10000	0	0
GCK	-0.1	0.26	-9999	-1.2	15	15
HK1	-0.33	0.46	-9999	-1.1	95	95
NPM1	-0.33	0.46	-9999	-1.1	95	95
EGLN1	-0.33	0.46	-9999	-1.1	96	96
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.33	0.46	-9999	-1.1	95	95
SMAD3	0.011	0.003	-9999	-10000	0	0
EDN1	-0.2	0.45	-9999	-1.2	83	83
IGFBP1	-0.36	0.49	-9999	-1.1	112	112
VEGFA	-0.24	0.35	-9999	-0.77	84	84
HIF1A/JAB1	-0.025	0.032	-9999	-10000	0	0
CP	-0.44	0.52	-9999	-1.1	149	149
CXCL12	-0.34	0.48	-9999	-1.1	103	103
COPS5	0.01	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.33	0.46	-9999	-1.1	95	95
EGLN3	-0.38	0.51	-9999	-1.1	125	125
CA9	-0.48	0.51	-9999	-1.1	152	152
TERT	-0.39	0.51	-9999	-1.1	118	118
ENO1	-0.33	0.46	-9999	-1.1	96	96
PFKL	-0.33	0.46	-9999	-1.1	96	96
NCOA1	0.01	0	-9999	-10000	0	0
ADM	-0.33	0.47	-9999	-1.1	96	96
ARNT	-0.041	0.071	-9999	-10000	0	0
HNF4A	-0.1	0.21	-9999	-0.51	112	112
ADFP	-0.33	0.46	-9999	-1	109	109
SLC2A1	-0.32	0.42	-9999	-0.86	124	124
LEP	-0.35	0.48	-9999	-1.1	105	105
HIF1A/ARNT/Cbp/p300	-0.28	0.38	-9999	-0.85	100	100
EPO	-0.14	0.26	-9999	-0.77	6	6
CREBBP	-0.045	0.11	-9999	-0.33	13	13
HIF1A/ARNT/Cbp/p300/HDAC7	-0.3	0.39	-9999	-0.89	98	98
PFKFB3	-0.33	0.46	-9999	-1.1	95	95
NT5E	-0.34	0.47	-9999	-1.1	103	103

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.057	0.069	0.13	237	-10000	0	237
BUB1B	-0.11	0.12	-10000	0	-0.22	239	239
PLK1	-0.024	0.048	-10000	0	-0.11	88	88
PLK1S1	-0.008	0.025	-10000	0	-0.11	1	1
KIF2A	-0.015	0.043	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.024	0.047	-10000	0	-0.11	88	88
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.21	0.25	-10000	0	-0.43	262	262
WEE1	-0.02	0.052	-10000	0	-0.18	1	1
cytokinesis	-0.11	0.12	-10000	0	-0.23	220	220
PP2A-alpha B56	-0.012	0.032	-10000	0	-10000	0	0
AURKA	-0.018	0.042	-10000	0	-0.17	1	1
PICH/PLK1	-0.13	0.21	-10000	0	-0.41	168	168
CENPE	-0.072	0.14	-10000	0	-0.34	107	107
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.015	0.043	-10000	0	-0.17	1	1
PPP2CA	0.01	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	-0.042	0.05	-10000	0	-0.11	70	70
PAK1	0.008	0.004	-10000	0	-10000	0	0
SPC24	-0.14	0.24	-10000	0	-0.51	152	152
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.034	0.056	-10000	0	-0.13	61	61
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	87	87
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.012	0.025	-10000	0	-0.058	78	78
G2 phase of mitotic cell cycle	-0.001	0.003	-10000	0	-0.01	3	3
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.011	-10000	0	-10000	0	0
spindle elongation	-0.024	0.047	-10000	0	-0.11	88	88
ODF2	0.008	0.004	-10000	0	-10000	0	0
BUB1	-0.02	0.038	-10000	0	-10000	0	0
TPT1	-0.008	0.025	-10000	0	-0.11	1	1
CDC25C	-0.061	0.058	-10000	0	-0.13	88	88
CDC25B	0.008	0.003	-10000	0	-10000	0	0
SGOL1	-0.057	0.069	-10000	0	-0.13	237	237
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.063	0.1	-10000	0	-0.24	102	102
CDC14B	0.007	0.003	-10000	0	-10000	0	0
CDC20	-0.29	0.26	-10000	0	-0.51	301	301
PLK1/PBIP1	-0.044	0.085	-10000	0	-0.33	36	36
mitosis	-0.003	0.008	0.019	22	-0.018	78	100
FBXO5	-0.015	0.042	-10000	0	-0.17	1	1
CDC2	-0.002	0.005	-10000	0	-0.011	105	105
NDC80	-0.24	0.26	-10000	0	-0.51	248	248
metaphase plate congression	-0.013	0.031	-10000	0	-10000	0	0
ERCC6L	-0.14	0.19	-10000	0	-0.4	158	158
NLP/gamma Tubulin	-0.01	0.026	-10000	0	-0.11	2	2
microtubule cytoskeleton organization	-0.008	0.025	-10000	0	-0.11	1	1
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-0.01	1	1
PPP1R12A	0.009	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-0.01	1	1
PLK1/PRC1-2	-0.19	0.21	-10000	0	-0.36	277	277
GRASP65/GM130/RAB1/GTP/PLK1	-0.016	0.026	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.014	0.044	-10000	0	-0.36	1	1
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.034	-10000	0	-10000	0	0
microtubule-based process	-0.16	0.17	-10000	0	-0.32	277	277
Golgi organization	-0.024	0.047	-10000	0	-0.11	88	88
Cohesin/SA2	-0.027	0.035	-10000	0	-0.16	1	1
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.27	0.26	-10000	0	-0.51	277	277
APC/C/CDC20	-0.18	0.17	-10000	0	-0.32	301	301
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.043	0.083	-10000	0	-0.32	36	36
PRC1	-0.062	0.18	-10000	0	-0.51	71	71
ECT2	-0.03	0.088	-10000	0	-0.35	30	30
C13orf34	-0.014	0.042	-10000	0	-0.36	1	1
NUDC	-0.013	0.031	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.11	0.11	-10000	0	-0.22	239	239
spindle assembly	-0.017	0.038	-10000	0	-0.088	70	70
spindle stabilization	-0.008	0.025	-10000	0	-0.11	1	1
APC/C/HCDH1	0.012	0.005	-10000	0	-10000	0	0
MKLP2/PLK1	-0.16	0.17	-10000	0	-0.32	277	277
CCNB1	-0.13	0.23	-10000	0	-0.51	140	140
PPP1CB	0.009	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	-0.007	0.032	-10000	0	-10000	0	0
TUBG1	-0.008	0.025	-10000	0	-0.11	2	2
G2/M transition of mitotic cell cycle	-0.063	0.099	-10000	0	-0.24	102	102
MLF1IP	-0.021	0.098	-10000	0	-0.38	36	36
INCENP	0.009	0.001	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.022	0.071	-9999	-0.25	45	45
RGS9BP	-0.066	0.18	-9999	-0.5	76	76
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.03	0.13	-9999	-0.51	35	35
mol:Na +	-0.16	0.18	-9999	-0.34	242	242
mol:ADP	-0.015	0.094	-9999	-0.36	35	35
GNAT2	0.007	0.023	-9999	-0.51	1	1
RGS9-1/Gbeta5/R9AP	-0.13	0.17	-9999	-0.33	210	210
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.019	-9999	-0.31	2	2
GRK7	0.006	0.005	-9999	-10000	0	0
CNGB3	-0.092	0.2	-9999	-0.51	97	97
Cone Metarhodopsin II/X-Arrestin	-0.002	0.028	-9999	-0.37	3	3
mol:Ca2+	-0.16	0.18	-9999	-0.32	265	265
Cone PDE6	-0.11	0.15	-9999	-0.5	27	27
Cone Metarhodopsin II	-0.019	0.07	-9999	-0.28	35	35
Na + (4 Units)	-0.16	0.18	-9999	-0.32	265	265
GNAT2/GDP	-0.11	0.14	-9999	-0.49	27	27
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.018	-9999	-0.28	2	2
Cone Transducin	-0.024	0.076	-9999	-0.27	45	45
SLC24A2	-0.033	0.14	-9999	-0.51	40	40
GNB3/GNGT2	-0.031	0.1	-9999	-0.36	44	44
GNB3	-0.023	0.13	-9999	-0.51	33	33
GNAT2/GTP	-0.001	0.016	-9999	-0.37	1	1
CNGA3	-0.17	0.25	-9999	-0.51	177	177
ARR3	-0.001	0.039	-9999	-0.51	3	3
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.16	0.18	-9999	-0.34	242	242
mol:Pi	-0.13	0.17	-9999	-0.32	210	210
Cone CNG Channel	-0.13	0.15	-9999	-0.46	40	40
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.033	0.14	-9999	-0.51	40	40
RGS9	-0.15	0.24	-9999	-0.5	160	160
PDE6C	0.003	0.004	-9999	-10000	0	0
GNGT2	-0.001	0.074	-9999	-0.5	11	11
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.023	-9999	-0.51	1	1

×

Signaling mediated by p38-alpha and p38-beta

Figure S11. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S11. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.093	0.32	-9999	-1	50	50
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.031	0.12	-9999	-0.29	86	86
ATF2/c-Jun	-0.014	0.12	-9999	-0.49	12	12
MAPK11	-0.034	0.13	-9999	-0.47	12	12
MITF	-0.036	0.16	-9999	-0.36	94	94
MAPKAPK5	-0.03	0.15	-9999	-0.34	89	89
KRT8	-0.031	0.15	-9999	-0.35	89	89
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.048	0.18	-9999	-0.43	89	89
CEBPB	-0.03	0.15	-9999	-0.34	89	89
SLC9A1	-0.03	0.15	-9999	-0.34	89	89
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.026	0.15	-9999	-0.34	89	89
p38alpha-beta/MNK1	-0.029	0.15	-9999	-0.34	89	89
JUN	-0.013	0.12	-9999	-0.48	12	12
PPARGC1A	-0.12	0.22	-9999	-0.37	192	192
USF1	-0.03	0.15	-9999	-0.34	89	89
RAB5/GDP/GDI1	-0.044	0.096	-9999	-0.38	12	12
NOS2	-0.092	0.32	-9999	-1	49	49
DDIT3	-0.032	0.15	-9999	-0.35	89	89
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.019	0.12	-9999	-0.45	13	13
p38alpha-beta/HBP1	-0.029	0.15	-9999	-0.34	89	89
CREB1	-0.031	0.16	-9999	-0.37	89	89
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.02	0.13	-9999	-0.46	12	12
RPS6KA4	-0.03	0.15	-9999	-0.34	89	89
PLA2G4A	-0.057	0.16	-9999	-0.51	21	21
GDI1	-0.03	0.15	-9999	-0.34	89	89
TP53	-0.041	0.18	-9999	-0.42	89	89
RPS6KA5	-0.032	0.15	-9999	-0.35	90	90
ESR1	-0.045	0.17	-9999	-0.38	95	95
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.03	0.15	-9999	-0.34	89	89
MEF2A	-0.03	0.15	-9999	-0.34	89	89
EIF4EBP1	-0.033	0.16	-9999	-0.37	89	89
KRT19	-0.034	0.15	-9999	-0.34	92	92
ELK4	-0.03	0.15	-9999	-0.34	89	89
ATF6	-0.03	0.15	-9999	-0.34	89	89
ATF1	-0.031	0.16	-9999	-0.37	89	89
p38alpha-beta/MAPKAPK2	-0.029	0.15	-9999	-0.34	89	89
p38alpha-beta/MAPKAPK3	-0.029	0.15	-9999	-0.34	89	89

×

IL4-mediated signaling events

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
BCL2L1	-0.45	0.52	-10000	0	-1.2	121	121
STAT6 (cleaved dimer)	-0.49	0.49	-10000	0	-1.1	164	164
IGHG1	-0.15	0.17	-10000	0	-0.38	11	11
IGHG3	-0.44	0.5	-10000	0	-1.1	153	153
AKT1	-0.18	0.24	-10000	0	-0.72	15	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.13	0.19	-10000	0	-0.82	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.19	0.24	-10000	0	-0.68	21	21
THY1	-0.46	0.52	-10000	0	-1.2	124	124
MYB	0.003	0.059	-10000	0	-0.5	7	7
HMGA1	-0.037	0.15	-10000	0	-0.51	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.24	0.28	-10000	0	-0.62	96	96
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.19	0.24	-10000	0	-0.65	29	29
SP1	0.015	0.004	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	3	3
SOCS5	0.021	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.47	0.49	-10000	0	-1.2	137	137
SOCS1	-0.27	0.33	-10000	0	-0.75	108	108
SOCS3	-0.2	0.26	-10000	0	-0.99	11	11
FCER2	-0.35	0.43	-10000	0	-0.99	100	100
PARP14	0.01	0.003	-10000	0	-10000	0	0
CCL17	-0.5	0.6	-10000	0	-1.4	132	132
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.15	0.2	-10000	0	-0.66	11	11
T cell proliferation	-0.44	0.53	-10000	0	-1.2	125	125
IL4R/JAK1	-0.45	0.52	-10000	0	-1.2	126	126
EGR2	-0.48	0.56	-10000	0	-1.3	124	124
JAK2	-0.013	0.045	-10000	0	-0.54	2	2
JAK3	0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.19	-10000	0	-0.67	17	17
CCL26	-0.47	0.53	-10000	0	-1.2	127	127
IL4R	-0.48	0.56	-10000	0	-1.3	124	124
PTPN6	0.02	0.013	-10000	0	-10000	0	0
IL13RA2	-0.5	0.57	-10000	0	-1.3	136	136
IL13RA1	-0.011	0.03	-10000	0	-10000	0	0
IRF4	-0.11	0.24	-10000	0	-0.92	28	28
ARG1	-0.12	0.18	-10000	0	-0.72	20	20
CBL	-0.22	0.26	-10000	0	-0.6	84	84
GTF3A	0.005	0.03	-10000	0	-0.5	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.015	0.049	-10000	0	-0.4	2	2
IRF4/BCL6	-0.094	0.22	-10000	0	-0.91	24	24
CD40LG	-0.009	0.11	-10000	0	-0.5	24	24
MAPK14	-0.22	0.27	-10000	0	-0.62	64	64
mitosis	-0.17	0.23	-10000	0	-0.67	15	15
STAT6	-0.53	0.62	-10000	0	-1.4	132	132
SPI1	-0.012	0.11	-10000	0	-0.5	25	25
RPS6KB1	-0.16	0.22	-10000	0	-0.68	12	12
STAT6 (dimer)	-0.53	0.62	-10000	0	-1.4	132	132
STAT6 (dimer)/PARP14	-0.49	0.57	-10000	0	-1.3	130	130
mast cell activation	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.2	0.26	-10000	0	-0.76	31	31
FRAP1	-0.18	0.24	-10000	0	-0.72	15	15
LTA	-0.45	0.52	-10000	0	-1.2	122	122
FES	0.009	0.022	-10000	0	-0.5	1	1
T-helper 1 cell differentiation	0.51	0.6	1.4	132	-10000	0	132
CCL11	-0.46	0.53	-10000	0	-1.2	130	130
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.18	0.24	-10000	0	-0.78	13	13
IL2RG	0.009	0.05	-10000	0	-0.49	5	5
IL10	-0.46	0.53	-10000	0	-1.2	125	125
IRS1	0.009	0.022	-10000	0	-0.5	1	1
IRS2	0.009	0.022	-10000	0	-0.5	1	1
IL4	-0.099	0.12	-10000	0	-10000	0	0
IL5	-0.46	0.52	-10000	0	-1.2	120	120
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.4	-10000	0	-0.91	124	124
COL1A1	-0.23	0.24	-10000	0	-0.63	59	59
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.54	-10000	0	-1.3	119	119
IL2R gamma/JAK3	0.014	0.036	-10000	0	-0.34	5	5
TFF3	-0.5	0.56	-10000	0	-1.3	137	137
ALOX15	-0.78	0.72	-10000	0	-1.4	271	271
MYBL1	0	0.071	-10000	0	-0.51	10	10
T-helper 2 cell differentiation	-0.36	0.4	-10000	0	-0.92	129	129
SHC1	0.008	0.032	-10000	0	-0.51	2	2
CEBPB	0.012	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.18	0.24	-10000	0	-0.62	28	28
mol:PI-3-4-5-P3	-0.18	0.24	-10000	0	-0.72	15	15
PI3K	-0.18	0.25	-10000	0	-0.77	15	15
DOK2	-0.033	0.14	-10000	0	-0.5	43	43
ETS1	0.019	0.025	-10000	0	-0.46	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.19	-10000	0	-0.65	10	10
ITGB3	-0.46	0.53	-10000	0	-1.2	125	125
PIGR	-0.6	0.68	-10000	0	-1.5	169	169
IGHE	0.034	0.041	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.19	-10000	0	-0.63	10	10
BCL6	0.01	0.003	-10000	0	-10000	0	0
OPRM1	-0.46	0.52	-10000	0	-1.2	123	123
RETNLB	-0.46	0.52	-10000	0	-1.2	125	125
SELP	-0.58	0.68	-10000	0	-1.5	160	160
AICDA	-0.47	0.54	-10000	0	-1.2	134	134

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.022	0.092	-9999	-0.41	24	24
alphaM/beta2 Integrin/GPIbA	-0.027	0.1	-9999	-0.39	32	32
alphaM/beta2 Integrin/proMMP-9	-0.086	0.15	-9999	-0.32	133	133
PLAUR	0.01	0	-9999	-10000	0	0
HMGB1	0.005	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.022	0.095	-9999	-0.43	23	23
AGER	-0.46	0.15	-9999	-0.51	466	466
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.008	0.094	-9999	-0.5	18	18
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.29	0.16	-9999	-0.5	134	134
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.1	0.21	-9999	-0.51	112	112
CYR61	-0.017	0.11	-9999	-0.5	27	27
TLN1	0.009	0.022	-9999	-0.5	1	1
Rap1/GTP	-0.084	0.14	-9999	-0.42	49	49
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.21	-9999	-0.5	115	115
MYH2	-0.15	0.2	-9999	-0.47	106	106
MST1R	0.008	0.032	-9999	-0.5	2	2
leukocyte activation during inflammatory response	-0.044	0.11	-9999	-0.3	72	72
APOB	-0.042	0.15	-9999	-0.5	51	51
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.009	0.023	-9999	-0.51	1	1
JAM3	0.005	0.05	-9999	-0.5	5	5
GP1BA	0	0.071	-9999	-0.5	10	10
alphaM/beta2 Integrin/CTGF	-0.038	0.12	-9999	-0.4	45	45
alphaM/beta2 Integrin	-0.088	0.18	-9999	-0.44	67	67
JAM3 homodimer	0.005	0.05	-9999	-0.5	5	5
ICAM2	0.005	0.05	-9999	-0.5	5	5
ICAM1	0.003	0.059	-9999	-0.5	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.087	0.18	-9999	-0.43	67	67
cell adhesion	-0.027	0.1	-9999	-0.39	32	32
NFKB1	-0.3	0.22	-9999	-0.6	141	141
THY1	-0.003	0.081	-9999	-0.51	13	13
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.032	0.094	-9999	-0.31	54	54
alphaM/beta2 Integrin/LRP/tPA	-0.05	0.13	-9999	-0.34	76	76
IL6	-0.35	0.33	-9999	-0.85	141	141
ITGB2	-0.005	0.072	-9999	-0.51	10	10
elevation of cytosolic calcium ion concentration	-0.065	0.13	-9999	-0.29	107	107
alphaM/beta2 Integrin/JAM2/JAM3	-0.05	0.14	-9999	-0.36	70	70
JAM2	-0.049	0.16	-9999	-0.5	59	59
alphaM/beta2 Integrin/ICAM1	-0.029	0.11	-9999	-0.44	22	22
alphaM/beta2 Integrin/uPA/Plg	-0.074	0.13	-9999	-0.3	123	123
RhoA/GTP	-0.1	0.19	-9999	-0.48	66	66
positive regulation of phagocytosis	-0.079	0.16	-9999	-0.64	30	30
Ron/MSP	-0.017	0.076	-9999	-0.36	24	24
alphaM/beta2 Integrin/uPAR/uPA	-0.066	0.13	-9999	-0.3	105	105
alphaM/beta2 Integrin/uPAR	-0.022	0.091	-9999	-0.42	23	23
PLAU	-0.084	0.2	-9999	-0.51	93	93
PLAT	-0.049	0.16	-9999	-0.51	58	58
actin filament polymerization	-0.15	0.19	-9999	-0.45	106	106
MST1	-0.012	0.1	-9999	-0.51	22	22
alphaM/beta2 Integrin/lipoprotein(a)	-0.045	0.11	-9999	-0.31	72	72
TNF	-0.28	0.23	-9999	-0.6	134	134
RAP1B	0.01	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.075	0.14	-9999	-0.33	114	114
fibrinolysis	-0.073	0.13	-9999	-0.3	123	123
HCK	-0.014	0.11	-9999	-0.5	24	24
dendritic cell antigen processing and presentation	-0.087	0.18	-9999	-0.43	67	67
VTN	-0.084	0.2	-9999	-0.5	95	95
alphaM/beta2 Integrin/CYR61	-0.037	0.12	-9999	-0.4	45	45
LPA	0	0.039	-9999	-0.5	3	3
LRP1	0.006	0.045	-9999	-0.5	4	4
cell migration	-0.076	0.13	-9999	-0.29	133	133
FN1	0.005	0.05	-9999	-0.5	5	5
alphaM/beta2 Integrin/Thy1	-0.029	0.1	-9999	-0.38	36	36
MPO	-0.006	0.088	-9999	-0.5	16	16
KNG1	-0.03	0.13	-9999	-0.51	35	35
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.093	0.18	-9999	-0.47	58	58
ELA2	0	0	-9999	-10000	0	0
PLG	-0.009	0.074	-9999	-0.51	11	11
CTGF	-0.019	0.12	-9999	-0.5	29	29
alphaM/beta2 Integrin/Hck	-0.034	0.14	-9999	-0.53	31	31
ITGAM	-0.017	0.1	-9999	-0.51	22	22
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.085	0.18	-9999	-0.54	41	41
HP	-0.14	0.23	-9999	-0.5	146	146
leukocyte adhesion	-0.27	0.19	-9999	-0.47	175	175
SELP	-0.1	0.21	-9999	-0.5	115	115

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.009	0.023	-9999	-0.51	1	1
LAT2	-0.093	0.2	-9999	-0.47	83	83
AP1	-0.13	0.21	-9999	-0.5	102	102
mol:PIP3	-0.099	0.22	-9999	-0.5	93	93
IKBKB	-0.044	0.13	-9999	-0.27	86	86
AKT1	-0.065	0.16	-9999	-0.38	81	81
IKBKG	-0.044	0.13	-9999	-0.26	91	91
MS4A2	-0.11	0.22	-9999	-0.5	122	122
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.002	-9999	-10000	0	0
MAP3K1	-0.067	0.18	-9999	-0.4	92	92
mol:Ca2+	-0.07	0.17	-9999	-0.37	93	93
LYN	0.008	0.005	-9999	-10000	0	0
CBLB	-0.088	0.19	-9999	-0.44	83	83
SHC1	0.008	0.032	-9999	-0.51	2	2
RasGAP/p62DOK	-0.025	0.077	-9999	-0.26	48	48
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.007	0.039	-9999	-0.5	3	3
PLD2	-0.097	0.19	-9999	-0.46	79	79
PTPN13	-0.11	0.22	-9999	-0.5	102	102
PTPN11	0.006	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.045	0.15	-9999	-0.32	81	81
SYK	0.005	0.041	-9999	-0.53	3	3
GRB2	0.009	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.2	-9999	-0.52	93	93
LAT	-0.088	0.19	-9999	-0.45	83	83
PAK2	-0.082	0.2	-9999	-0.46	92	92
NFATC2	-0.073	0.16	-9999	-0.75	23	23
HRAS	-0.096	0.22	-9999	-0.5	93	93
GAB2	0.005	0.05	-9999	-0.5	5	5
PLA2G1B	-0.001	0.031	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.22	-9999	-0.4	192	192
Antigen/IgE/Fc epsilon R1	-0.14	0.2	-9999	-0.37	192	192
mol:GDP	-0.11	0.24	-9999	-0.54	96	96
JUN	0.007	0.039	-9999	-0.5	3	3
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.008	0.023	-9999	-0.5	1	1
FOS	-0.017	0.11	-9999	-0.5	27	27
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.18	-9999	-0.39	127	127
CHUK	-0.044	0.13	-9999	-0.26	91	91
KLRG1	-0.084	0.18	-9999	-0.42	82	82
VAV1	-0.091	0.19	-9999	-0.46	83	83
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.088	0.19	-9999	-0.44	83	83
negative regulation of mast cell degranulation	-0.074	0.17	-9999	-0.4	81	81
BTK	-0.12	0.27	-9999	-0.5	133	133
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.58	78	78
GAB2/PI3K/SHP2	-0.1	0.16	-9999	-0.42	81	81
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.099	0.2	-9999	-0.49	82	82
RAF1	0.021	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.19	-9999	-0.5	78	78
FCER1G	-0.002	0.085	-9999	-0.51	14	14
FCER1A	-0.13	0.23	-9999	-0.51	139	139
Antigen/IgE/Fc epsilon R1/Fyn	-0.13	0.18	-9999	-0.38	145	145
MAPK3	0.028	0.02	-9999	-10000	0	0
MAPK1	0.028	0.02	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.012	0.061	-9999	-10000	0	0
DUSP1	-0.038	0.15	-9999	-0.5	48	48
NF-kappa-B/RelA	-0.043	0.062	-9999	-0.22	10	10
actin cytoskeleton reorganization	-0.096	0.2	-9999	-0.48	80	80
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.18	-9999	-0.45	90	90
FER	-0.088	0.19	-9999	-0.44	83	83
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.038	0.089	-9999	-0.53	13	13
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.11	0.24	-9999	-0.55	92	92
cytokine secretion	-0.032	0.045	-9999	-10000	0	0
SPHK1	-0.09	0.19	-9999	-0.45	84	84
PTK2	-0.1	0.21	-9999	-0.5	80	80
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.22	-9999	-0.54	93	93
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.095	0.22	-9999	-0.49	93	93
MAP2K2	0.025	0.02	-9999	-10000	0	0
MAP2K1	0.025	0.02	-9999	-10000	0	0
MAP2K7	0.01	0	-9999	-10000	0	0
KLRG1/SHP2	-0.093	0.15	-9999	-0.38	81	81
MAP2K4	0.011	0.011	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.14	0.2	-9999	-0.4	145	145
mol:Choline	-0.096	0.18	-9999	-0.45	79	79
SHC/Grb2/SOS1	-0.1	0.16	-9999	-0.42	80	80
FYN	0.009	0.022	-9999	-0.5	1	1
DOK1	0.01	0	-9999	-10000	0	0
PXN	-0.088	0.19	-9999	-0.46	80	80
HCLS1	-0.09	0.19	-9999	-0.45	83	83
PRKCB	-0.072	0.17	-9999	-0.38	93	93
FCGR2B	0.009	0.022	-9999	-0.5	1	1
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.075	0.17	-9999	-0.4	81	81
LCP2	0.006	0.039	-9999	-0.5	3	3
PLA2G4A	-0.12	0.21	-9999	-0.48	102	102
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.096	0.18	-9999	-0.45	79	79
IKK complex	-0.021	0.098	-9999	-0.19	83	83
WIPF1	0.01	0	-9999	-10000	0	0

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.078	0.13	-9999	-0.5	19	19
SMAD6-7/SMURF1	-0.038	0.1	-9999	-0.3	67	67
NOG	-0.026	0.13	-9999	-0.5	36	36
SMAD9	-0.12	0.2	-9999	-0.48	114	114
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.027	0.12	-9999	-0.36	26	26
BMP7/USAG1	-0.28	0.19	-9999	-0.39	369	369
SMAD5/SKI	-0.02	0.11	-9999	-0.43	11	11
SMAD1	0.023	0.029	-9999	-10000	0	0
BMP2	-0.061	0.18	-9999	-0.5	71	71
SMAD1/SMAD1/SMAD4	-0.025	0.065	-9999	-0.41	1	1
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.044	0.16	-9999	-0.5	54	54
BMPR1A-1B/BAMBI	-0.043	0.11	-9999	-0.31	72	72
AHSG	-0.034	0.14	-9999	-0.51	39	39
CER1	-0.004	0.055	-9999	-0.51	6	6
BMP2-4/CER1	-0.053	0.12	-9999	-0.32	85	85
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.019	0.12	-9999	-0.46	15	15
BMP2-4 (homodimer)	-0.059	0.14	-9999	-0.38	81	81
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.065	0.13	-9999	-0.52	18	18
RGMA	0.001	0.068	-9999	-0.51	9	9
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.026	0.11	-9999	-0.37	24	24
BMP2-4/USAG1	-0.24	0.18	-9999	-0.34	363	363
SMAD6/SMURF1/SMAD5	-0.02	0.11	-9999	-0.43	11	11
SOSTDC1	-0.33	0.24	-9999	-0.5	346	346
BMP7/BMPR2/BMPR1A-1B	-0.061	0.12	-9999	-0.52	8	8
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.064	0.18	-9999	-0.5	75	75
HFE2	-0.006	0.078	-9999	-0.51	12	12
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.063	0.14	-9999	-0.32	101	101
SMAD5/SMAD5/SMAD4	-0.02	0.11	-9999	-0.43	11	11
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.041	0.083	-9999	-0.35	16	16
BMP7 (homodimer)	-0.057	0.17	-9999	-0.5	67	67
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.079	0.16	-9999	-0.37	109	109
SMAD1/SKI	0.027	0.027	-9999	-10000	0	0
SMAD6	-0.057	0.17	-9999	-0.5	67	67
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.072	0.14	-9999	-0.32	114	114
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.34	0.24	-9999	-0.51	349	349
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.018	-9999	-0.29	2	2
BMPR1A-1B (homodimer)	-0.037	0.11	-9999	-0.35	54	54
CHRDL1	-0.18	0.24	-9999	-0.5	187	187
ENDOFIN/SMAD1	0.027	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.029	0.074	-9999	-0.46	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	-0.012	0.1	-9999	-0.51	22	22
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.2	-9999	-0.37	215	215
BMP2-4/GREM1	-0.25	0.18	-9999	-0.34	375	375
SMAD7	0.009	0.022	-9999	-0.5	1	1
SMAD8A/SMAD8A/SMAD4	-0.092	0.2	-9999	-0.45	114	114
SMAD1/SMAD6	0.027	0.027	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.057	0.17	-9999	-0.5	67	67
BMP6	-0.064	0.18	-9999	-0.5	75	75
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.02	0.11	-9999	-0.37	19	19
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.027	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.016	-9999	-0.35	1	1
CTDSPL	0.01	0	-9999	-10000	0	0
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.008	0.032	-9999	-0.5	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.04	0.13	-9999	-0.38	37	37
CHRD	-0.015	0.11	-9999	-0.51	25	25
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.032	0.12	-9999	-0.4	24	24
BMP4	-0.006	0.089	-9999	-0.5	16	16
FST	-0.036	0.15	-9999	-0.5	46	46
BMP2-4/NOG	-0.069	0.15	-9999	-0.34	104	104
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.056	0.11	-9999	-0.49	8	8

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.024	0.13	-10000	0	-0.47	38	38
CDKN2C	0.022	0.031	-10000	0	-0.45	1	1
CDKN2A	-0.15	0.24	-10000	0	-0.52	152	152
CCND2	0.041	0.066	0.2	38	-0.12	5	43
RB1	-0.045	0.068	-10000	0	-0.21	38	38
CDK4	0.049	0.071	0.21	39	-10000	0	39
CDK6	0.047	0.071	0.22	37	-10000	0	37
G1/S progression	0.037	0.073	0.2	39	-10000	0	39

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.033	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.085	0.12	-9999	-0.36	33	33
JUN	-0.052	0.12	-9999	-0.34	27	27
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.12	0.16	-9999	-0.41	50	50
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.032	-9999	-0.51	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.12	0.16	-9999	-0.41	50	50
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.084	0.13	-9999	-0.27	158	158
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.1	0.14	-9999	-0.47	27	27
GRB7	0.004	0.055	-9999	-0.5	6	6
RET51/GFRalpha1/GDNF	-0.12	0.16	-9999	-0.41	50	50
MAPKKK cascade	-0.095	0.13	-9999	-0.43	30	30
BCAR1	0.009	0.022	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.084	0.13	-9999	-0.27	158	158
lamellipodium assembly	-0.082	0.11	-9999	-0.33	33	33
RET51/GFRalpha1/GDNF/SHC	-0.12	0.16	-9999	-0.3	206	206
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.085	0.13	-9999	-0.28	158	158
RET9/GFRalpha1/GDNF/Shank3	-0.087	0.14	-9999	-0.28	159	159
MAPK3	-0.078	0.14	-9999	-0.45	27	27
DOK1	0.01	0	-9999	-10000	0	0
DOK6	-0.043	0.16	-9999	-0.5	53	53
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.075	0.15	-9999	-0.37	59	59
DOK5	-0.065	0.18	-9999	-0.51	74	74
GFRA1	-0.14	0.23	-9999	-0.5	152	152
MAPK8	-0.059	0.12	-9999	-0.35	25	25
HRAS/GTP	-0.11	0.14	-9999	-0.47	27	27
tube development	-0.08	0.12	-9999	-0.27	88	88
MAPK1	-0.078	0.14	-9999	-0.45	27	27
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.055	0.12	-9999	-0.23	151	151
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PDLIM7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.18	-9999	-0.53	59	59
SHC1	0.008	0.032	-9999	-0.51	2	2
RET51/GFRalpha1/GDNF/Dok4	-0.12	0.16	-9999	-0.41	50	50
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.18	-9999	-0.56	45	45
PRKCA	0.008	0.032	-9999	-0.5	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.071	0.14	-9999	-0.28	151	151
PIK3R1	0.009	0.022	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.056	0.12	-9999	-0.24	151	151
RET51/GFRalpha1/GDNF/Grb7	-0.12	0.16	-9999	-0.32	149	149
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.063	0.18	-9999	-0.51	72	72
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.051	0.12	-9999	-0.34	27	27
RET9/GFRalpha1/GDNF/FRS2	-0.085	0.13	-9999	-0.27	160	160
SHANK3	0.003	0.059	-9999	-0.5	7	7
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.055	0.12	-9999	-0.24	151	151
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.071	0.13	-9999	-0.37	26	26
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.07	0.13	-9999	-0.37	26	26
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.073	0.14	-9999	-0.41	28	28
PI3K	-0.09	0.19	-9999	-0.51	33	33
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.08	0.12	-9999	-0.27	88	88
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.065	0.12	-9999	-0.34	25	25
RET51/GFRalpha1/GDNF/FRS2	-0.12	0.16	-9999	-0.53	27	27
GAB1	0.008	0.032	-9999	-0.5	2	2
IRS1	0.009	0.022	-9999	-0.5	1	1
IRS2	0.009	0.022	-9999	-0.5	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.074	0.14	-9999	-0.42	30	30
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.16	-9999	-0.32	146	146
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.004	0.067	-9999	-0.51	9	9
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.54	27	27
Rac1/GTP	-0.095	0.13	-9999	-0.4	33	33
RET9/GFRalpha1/GDNF	-0.094	0.14	-9999	-0.31	158	158
GFRalpha1/GDNF	-0.11	0.17	-9999	-0.36	158	158

×

Glucocorticoid receptor regulatory network

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
PCK2	0.029	0.085	0.33	2	-10000	0	2
SMARCC2	0.011	0.005	-10000	0	-10000	0	0
SMARCC1	0.011	0.005	-10000	0	-10000	0	0
TBX21	-0.1	0.22	-10000	0	-0.55	64	64
SUMO2	0.009	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0	-10000	0	-10000	0	0
FKBP4	0.009	0.023	-10000	0	-0.51	1	1
FKBP5	0.008	0.032	-10000	0	-0.5	2	2
GR alpha/HSP90/FKBP51/HSP90	0.089	0.11	0.28	64	-10000	0	64
PRL	-0.067	0.13	-10000	0	-0.59	5	5
cortisol/GR alpha (dimer)/TIF2	0.21	0.26	0.54	145	-10000	0	145
RELA	-0.034	0.089	-10000	0	-0.27	2	2
FGG	0	0.33	0.46	72	-0.46	126	198
GR beta/TIF2	0.092	0.12	0.31	71	-0.25	4	75
IFNG	-0.23	0.28	-10000	0	-0.66	104	104
apoptosis	-0.011	0.15	0.47	11	-0.57	13	24
CREB1	-0.006	0.048	-10000	0	-10000	0	0
histone acetylation	-0.029	0.14	0.27	7	-0.34	43	50
BGLAP	-0.064	0.13	-10000	0	-0.5	8	8
GR/PKAc	0.088	0.1	0.27	60	-10000	0	60
NF kappa B1 p50/RelA	-0.059	0.16	-10000	0	-0.43	30	30
SMARCD1	0.011	0.005	-10000	0	-10000	0	0
MDM2	0.076	0.097	0.24	78	-0.23	1	79
GATA3	0.012	0.039	-10000	0	-0.5	3	3
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.13	0.32	-10000	0	-1.1	47	47
GSK3B	0.009	0.005	-10000	0	-10000	0	0
NR1I3	0.012	0.14	0.47	9	-0.61	4	13
CSN2	0.12	0.17	0.38	69	-10000	0	69
BRG1/BAF155/BAF170/BAF60A	0.02	0.025	-10000	0	-0.32	1	1
NFATC1	0.007	0.05	-10000	0	-0.5	5	5
POU2F1	0.01	0.014	-10000	0	-10000	0	0
CDKN1A	0.024	0.059	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.005	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.51	10	10
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.087	0.1	0.28	53	-10000	0	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.014	0.21	0.45	9	-0.81	28	37
JUN	-0.17	0.18	-10000	0	-0.45	104	104
IL4	-0.078	0.15	-10000	0	-0.55	16	16
CDK5R1	-0.007	0.09	-10000	0	-0.51	16	16
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.12	0.22	0.21	1	-0.47	91	92
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.091	0.1	0.28	52	-10000	0	52
cortisol/GR alpha (monomer)	0.24	0.32	0.64	152	-0.37	1	153
NCOA2	0.005	0.05	-10000	0	-0.5	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.069	0.13	-10000	0	-0.57	27	27
AP-1/NFAT1-c-4	-0.28	0.28	-10000	0	-0.64	151	151
AFP	-0.14	0.16	-10000	0	-0.61	18	18
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.13	0.15	0.42	48	-10000	0	48
TP53	0.026	0.022	-10000	0	-0.48	1	1
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.26	0.33	-10000	0	-0.74	125	125
KRT14	-0.18	0.2	-10000	0	-0.53	65	65
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.053	0.062	0.21	5	-0.26	1	6
HDAC1	0.007	0.004	-10000	0	-10000	0	0
HDAC2	0.015	0.024	-10000	0	-10000	0	0
AP-1	-0.28	0.28	-10000	0	-0.64	151	151
MAPK14	0.009	0.005	-10000	0	-10000	0	0
MAPK10	-0.046	0.16	-10000	0	-0.5	56	56
MAPK11	0.006	0.039	-10000	0	-0.5	3	3
KRT5	-0.41	0.5	-10000	0	-1.1	160	160
interleukin-1 receptor activity	0.006	0.024	-10000	0	-10000	0	0
NCOA1	0.012	0.001	-10000	0	-10000	0	0
STAT1	0.016	0	-10000	0	-10000	0	0
CGA	-0.11	0.19	-10000	0	-0.54	47	47
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.19	0.47	78	-10000	0	78
MAPK3	0.009	0.005	-10000	0	-10000	0	0
MAPK1	0.009	0.005	-10000	0	-10000	0	0
ICAM1	-0.14	0.24	-10000	0	-0.6	64	64
NFKB1	-0.034	0.089	-10000	0	-0.25	20	20
MAPK8	-0.15	0.17	-10000	0	-0.42	96	96
MAPK9	0.009	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.015	0.15	0.48	10	-0.6	13	23
BAX	0.026	0.021	-10000	0	-10000	0	0
POMC	-0.18	0.31	-10000	0	-0.97	42	42
EP300	0.053	0.062	-10000	0	-0.26	1	1
cortisol/GR alpha (dimer)/p53	0.22	0.26	0.55	152	-10000	0	152
proteasomal ubiquitin-dependent protein catabolic process	0.052	0.075	0.22	31	-0.2	1	32
SGK1	0.097	0.092	0.38	1	-1.1	1	2
IL13	-0.16	0.19	-10000	0	-0.62	31	31
IL6	-0.3	0.45	-10000	0	-0.97	143	143
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.14	0.16	-10000	0	-0.62	9	9
IL2	-0.21	0.23	-10000	0	-0.59	90	90
CDK5	0.009	0.003	-10000	0	-10000	0	0
PRKACB	0.009	0.023	-10000	0	-0.51	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.14	0.23	-10000	0	-0.65	44	44
CDK5R1/CDK5	-0.01	0.063	-10000	0	-0.36	16	16
NF kappa B1 p50/RelA/PKAc	-0.026	0.12	-10000	0	-0.36	15	15
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	147	-10000	0	147
SMARCA4	0.01	0.023	-10000	0	-0.5	1	1
chromatin remodeling	0.14	0.15	0.36	95	-10000	0	95
NF kappa B1 p50/RelA/Cbp	0.009	0.15	0.36	8	-0.37	16	24
JUN (dimer)	-0.17	0.18	-10000	0	-0.45	104	104
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.34	0.43	-10000	0	-0.86	204	204
NR3C1	0.14	0.19	0.43	99	-10000	0	99
NR4A1	-0.1	0.22	-10000	0	-0.5	117	117
TIF2/SUV420H1	-0.003	0.035	-10000	0	-0.35	5	5
MAPKKK cascade	-0.011	0.15	0.47	11	-0.57	13	24
cortisol/GR alpha (dimer)/Src-1	0.22	0.26	0.54	147	-10000	0	147
PBX1	-0.005	0.087	-10000	0	-0.5	15	15
POU1F1	0.002	0.031	-10000	0	-0.6	1	1
SELE	-0.26	0.43	-10000	0	-1.1	105	105
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.15	0.36	95	-10000	0	95
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	147	-10000	0	147
mol:cortisol	0.13	0.19	0.38	144	-0.21	13	157
MMP1	-0.26	0.19	-10000	0	-0.44	176	176

×

TCGA08_p53

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
CDKN2A	-0.1	0.17	-10000	0	-0.37	152	152
TP53	-0.027	0.044	-10000	0	-10000	0	0
Senescence	-0.027	0.044	-10000	0	-10000	0	0
Apoptosis	-0.027	0.044	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.052	0.086	0.18	151	-0.33	2	153
MDM4	0.01	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.17	0.14	-9999	-0.51	22	22
NF kappa B1 p50/RelA/I kappa B alpha	-0.15	0.11	-9999	-0.45	22	22
alphaV/beta3 Integrin/Osteopontin/Src	-0.25	0.16	-9999	-0.36	359	359
AP1	-0.16	0.12	-9999	-0.47	25	25
ILK	-0.18	0.15	-9999	-0.53	22	22
bone resorption	-0.15	0.11	-9999	-0.43	27	27
PTK2B	0.008	0.032	-9999	-0.5	2	2
PYK2/p130Cas	-0.17	0.12	-9999	-0.48	25	25
ITGAV	0.011	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.006	0.046	-9999	-0.35	9	9
alphaV/beta3 Integrin/Osteopontin	-0.22	0.15	-9999	-0.39	89	89
MAP3K1	-0.18	0.15	-9999	-0.54	22	22
JUN	0.007	0.039	-9999	-0.5	3	3
MAPK3	-0.17	0.15	-9999	-0.38	88	88
MAPK1	-0.17	0.15	-9999	-0.38	88	88
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.16	0.14	-9999	-0.5	22	22
ITGB3	-0.017	0.12	-9999	-0.51	28	28
NFKBIA	-0.15	0.15	-9999	-0.36	86	86
FOS	-0.017	0.11	-9999	-0.5	27	27
CD44	0.001	0.067	-9999	-0.5	9	9
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.16	0.18	-9999	-0.64	13	13
NF kappa B1 p50/RelA	-0.15	0.12	-9999	-0.47	22	22
BCAR1	0.009	0.022	-9999	-0.5	1	1
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.019	0.081	-9999	-0.36	28	28
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.18	0.15	-9999	-0.54	22	22
VAV3	-0.17	0.14	-9999	-0.51	26	26
MAP3K14	-0.19	0.16	-9999	-0.38	88	88
ROCK2	0.01	0	-9999	-10000	0	0
SPP1	-0.35	0.24	-9999	-0.5	359	359
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.16	0.12	-9999	-0.46	26	26
MMP2	-0.12	0.13	-9999	-0.43	16	16

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.22	0.32	-10000	0	-0.88	43	43
PCK1	-0.17	0.23	-10000	0	-0.72	30	30
HNF4A	-0.4	0.49	-10000	0	-1.1	115	115
KCNJ11	-0.19	0.33	-10000	0	-0.94	43	43
AKT1	-0.074	0.14	-10000	0	-0.43	4	4
response to starvation	-0.028	0.047	-10000	0	-10000	0	0
DLK1	-0.21	0.32	-10000	0	-0.95	35	35
NKX2-1	-0.11	0.38	0.46	1	-1.3	38	39
ACADM	-0.22	0.32	-10000	0	-0.89	42	42
TAT	-0.16	0.22	-10000	0	-0.72	26	26
CEBPB	0.009	0.005	-10000	0	-10000	0	0
CEBPA	-0.016	0.11	-10000	0	-0.5	26	26
TTR	-0.2	0.25	-10000	0	-0.74	52	52
PKLR	-0.22	0.32	-10000	0	-0.91	43	43
APOA1	-0.5	0.63	-10000	0	-1.3	166	166
CPT1C	-0.22	0.32	-10000	0	-0.94	41	41
ALAS1	-0.075	0.16	-10000	0	-10000	0	0
TFRC	-0.16	0.25	-10000	0	-1.1	9	9
FOXF1	-0.1	0.21	0.22	2	-0.48	119	121
NF1	0.015	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.11	0.23	-10000	0	-0.56	105	105
CPT1A	-0.22	0.32	-10000	0	-0.89	42	42
HMGCS1	-0.22	0.32	-10000	0	-0.89	42	42
NR3C1	0.004	0.032	-10000	0	-10000	0	0
CPT1B	-0.22	0.32	-10000	0	-0.88	46	46
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.001	0.025	-10000	0	-10000	0	0
GCK	-0.23	0.34	-10000	0	-0.91	52	52
CREB1	0.005	0.02	-10000	0	-10000	0	0
IGFBP1	-0.13	0.19	-10000	0	-0.59	22	22
PDX1	-0.16	0.25	-10000	0	-0.72	33	33
UCP2	-0.22	0.32	-10000	0	-0.89	42	42
ALDOB	-0.2	0.34	-10000	0	-0.93	41	41
AFP	-0.071	0.14	-10000	0	-0.5	20	20
BDH1	-0.22	0.32	-10000	0	-0.9	42	42
HADH	-0.18	0.31	-10000	0	-0.92	31	31
F2	-0.32	0.43	-10000	0	-1.1	60	60
HNF1A	-0.11	0.23	-10000	0	-0.56	105	105
G6PC	-0.08	0.15	-10000	0	-0.6	13	13
SLC2A2	-0.15	0.23	-10000	0	-0.67	28	28
INS	0	0.027	-10000	0	-10000	0	0
FOXA1	-0.012	0.11	0.25	8	-0.54	12	20
FOXA3	-0.16	0.27	-10000	0	-0.57	146	146
FOXA2	-0.21	0.36	-10000	0	-0.98	44	44
ABCC8	-0.25	0.41	-10000	0	-0.98	84	84
ALB	-0.082	0.16	-10000	0	-0.47	33	33

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.051	-9999	-0.37	10	10
Metarhodopsin II/Arrestin	-0.001	0.014	-9999	-0.31	1	1
PDE6G/GNAT1/GTP	-0.009	0.058	-9999	-0.34	14	14
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.007	0.071	-9999	-0.51	10	10
GRK1	-0.03	0.13	-9999	-0.51	35	35
CNG Channel	-0.1	0.15	-9999	-0.48	40	40
mol:Na +	-0.12	0.15	-9999	-0.48	41	41
mol:ADP	-0.03	0.13	-9999	-0.51	35	35
RGS9-1/Gbeta5/R9AP	-0.13	0.17	-9999	-0.33	210	210
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.15	-9999	-0.5	41	41
CNGB1	-0.086	0.2	-9999	-0.51	95	95
RDH5	0.002	0.064	-9999	-0.51	8	8
SAG	0.001	0.023	-9999	-0.51	1	1
mol:Ca2+	-0.092	0.16	-9999	-0.47	41	41
Na + (4 Units)	-0.11	0.14	-9999	-0.45	41	41
RGS9	-0.15	0.24	-9999	-0.5	160	160
GNB1/GNGT1	-0.073	0.14	-9999	-0.36	104	104
GNAT1/GDP	-0.12	0.15	-9999	-0.5	31	31
GUCY2D	-0.001	0.071	-9999	-0.5	10	10
GNGT1	-0.098	0.21	-9999	-0.51	104	104
GUCY2F	0	0.032	-9999	-0.51	2	2
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.014	0.095	-9999	-0.26	63	63
mol:11-cis-retinal	0.002	0.064	-9999	-0.51	8	8
mol:cGMP	-0.053	0.11	-9999	-0.51	6	6
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	-0.006	0.045	-9999	-0.36	8	8
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.059	0.18	-9999	-0.51	68	68
Metarhodopsin II	-0.019	0.07	-9999	-0.28	35	35
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.055	0.12	-9999	-0.29	92	92
RGS9BP	-0.066	0.18	-9999	-0.5	76	76
Metarhodopsin II/Transducin	-0.021	0.061	-9999	-0.22	3	3
GCAP Family/Ca ++	-0.051	0.11	-9999	-0.29	91	91
PDE6A/B	-0.035	0.1	-9999	-0.35	51	51
mol:Pi	-0.13	0.17	-9999	-0.32	210	210
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.061	0.12	-9999	-0.28	111	111
PDE6B	0.001	0.067	-9999	-0.5	9	9
PDE6A	-0.032	0.14	-9999	-0.5	42	42
PDE6G	0.004	0.055	-9999	-0.5	6	6
RHO	0.004	0.005	-9999	-10000	0	0
PDE6	-0.13	0.16	-9999	-0.48	58	58
GUCA1A	-0.08	0.19	-9999	-0.51	88	88
GC2/GCAP Family	-0.052	0.11	-9999	-0.3	65	65
GUCA1C	-0.001	0.022	-9999	-0.51	1	1
GUCA1B	0.003	0.06	-9999	-0.51	7	7

×

Arf6 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
CENTA1/KIF3B	-0.002	0.023	-9999	-0.3	3	3
ARNO/beta Arrestin1-2	-0.095	0.11	-9999	-0.36	22	22
EGFR	-0.006	0.089	-9999	-0.5	16	16
EPHA2	0	0.07	-9999	-0.5	10	10
USP6	0.01	0	-9999	-10000	0	0
IQSEC1	0.009	0.022	-9999	-0.5	1	1
EGFR/EGFR/EGF/EGF	-0.08	0.15	-9999	-0.37	111	111
ARRB2	-0.007	0.056	-9999	-0.18	46	46
mol:GTP	0.012	0.021	-9999	-0.13	2	2
ARRB1	0.004	0.055	-9999	-0.5	6	6
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	-0.045	0.16	-9999	-0.51	54	54
EGF	-0.09	0.2	-9999	-0.51	99	99
somatostatin receptor activity	0	0	-9999	-0.001	94	94
ARAP2	-0.008	0.094	-9999	-0.5	18	18
mol:GDP	-0.089	0.12	-9999	-0.26	125	125
mol:PI-3-4-5-P3	0	0	-9999	-0.001	73	73
ITGA2B	-0.044	0.16	-9999	-0.5	54	54
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.037	-9999	-0.26	11	11
ADAP1	0.009	0.022	-9999	-0.5	1	1
KIF13B	0.008	0.032	-9999	-0.5	2	2
HGF/MET	-0.044	0.12	-9999	-0.37	62	62
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.084	0.11	-9999	-0.26	92	92
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.067	0.13	-9999	-0.31	111	111
ADRB2	-0.19	0.25	-9999	-0.5	201	201
receptor agonist activity	0	0	-9999	0	127	127
actin filament binding	0	0	-9999	0	129	129
SRC	0.01	0	-9999	-10000	0	0
ITGB3	-0.018	0.12	-9999	-0.51	28	28
GNAQ	0.009	0.022	-9999	-0.5	1	1
EFA6/PI-4-5-P2	0	0	-9999	-0.001	89	89
ARF6/GDP	-0.011	0.074	-9999	-0.37	8	8
ARF6/GDP/GULP/ACAP1	-0.082	0.099	-9999	-0.31	37	37
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.041	0.096	-9999	-0.26	81	81
ACAP1	0.008	0.032	-9999	-0.5	2	2
ACAP2	0.009	0.023	-9999	-0.51	1	1
LHCGR/beta Arrestin2	-0.022	0.077	-9999	-0.27	46	46
EFNA1	0.009	0.022	-9999	-0.5	1	1
HGF	-0.021	0.12	-9999	-0.5	31	31
CYTH3	0.007	0.023	-9999	-0.37	2	2
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	81	81
endosomal lumen acidification	0	0	-9999	0	33	33
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.006	0.045	-9999	-0.5	4	4
GNAQ/ARNO	0.006	0.013	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	25	25
MET	-0.024	0.13	-9999	-0.5	34	34
GNA14	-0.004	0.083	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	89	89
GNA11	0.008	0.032	-9999	-0.5	2	2
LHCGR	-0.041	0.15	-9999	-0.51	46	46
AGTR1	-0.16	0.24	-9999	-0.5	167	167
desensitization of G-protein coupled receptor protein signaling pathway	-0.021	0.077	-9999	-0.27	46	46
IPCEF1/ARNO	-0.044	0.1	-9999	-0.46	4	4
alphaIIb/beta3 Integrin	-0.056	0.13	-9999	-0.36	81	81

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.001	0.073	-9999	-0.31	27	27
ADCY5	-0.031	0.12	-9999	-0.31	73	73
ADCY6	0.011	0.036	-9999	-0.3	7	7
ADCY7	0.011	0.039	-9999	-0.3	8	8
ADCY1	0.006	0.055	-9999	-0.3	16	16
ADCY2	-0.024	0.11	-9999	-0.3	63	63
ADCY3	0.012	0.034	-9999	-0.3	6	6
ADCY8	-0.12	0.15	-9999	-0.3	207	207
PRKCE	0.005	0.04	-9999	-0.36	6	6
ADCY9	0.006	0.055	-9999	-0.3	16	16
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.061	0.098	-9999	-0.35	28	28

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.019	-10000	0	-10000	0	0
AES	0.003	0.016	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	-0.097	0.21	-10000	0	-0.5	108	108
TLE1	0.003	0.016	-10000	0	-10000	0	0
MACF1	0.006	0.045	-10000	0	-0.5	4	4
CTNNB1	0.088	0.08	0.24	18	-0.28	1	19
WIF1	-0.34	0.24	-10000	0	-0.5	356	356
beta catenin/RanBP3	0.013	0.088	0.39	24	-10000	0	24
KREMEN2	-0.12	0.22	-10000	0	-0.51	128	128
DKK1	-0.12	0.23	-10000	0	-0.5	135	135
beta catenin/beta TrCP1	0.089	0.075	0.23	17	-10000	0	17
FZD1	0.01	0.001	-10000	0	-10000	0	0
AXIN2	-0.026	0.24	-10000	0	-1.3	18	18
AXIN1	0.011	0.001	-10000	0	-10000	0	0
RAN	0.009	0.023	-10000	0	-0.51	1	1
Axin1/APC/GSK3/beta catenin	0.005	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.073	0.06	0.27	1	-10000	0	1
Axin1/APC/GSK3	0.021	0.061	0.2	46	-10000	0	46
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.046	-10000	0	-10000	0	0
HNF1A	-0.1	0.21	-10000	0	-0.51	105	105
CTBP1	0.004	0.017	-10000	0	-10000	0	0
MYC	0.006	0.1	-10000	0	-1.4	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.13	0.19	-10000	0	-0.36	194	194
NKD1	-0.053	0.17	-10000	0	-0.5	63	63
TCF4	0.002	0.036	-10000	0	-0.5	2	2
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.006	0.039	-10000	0	-0.26	5	5
Ran/GTP	0	0.016	-10000	0	-0.37	1	1
CtBP/CBP/TCF/TLE1/AES	0.002	0.11	0.44	25	-10000	0	25
LEF1	0.003	0.028	-10000	0	-0.51	1	1
DVL1	0.074	0.052	0.19	1	-0.27	1	2
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.075	0.066	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.35	223	223
LRP6	0.01	0.001	-10000	0	-10000	0	0
CSNK1A1	0.004	0.019	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.005	0.16	-10000	0	-1.3	7	7
WNT1	-0.002	0.078	-10000	0	-0.51	12	12
GSK3A	0.011	0.001	-10000	0	-10000	0	0
GSK3B	0.01	0.001	-10000	0	-10000	0	0
FRAT1	0.009	0.002	-10000	0	-10000	0	0
PPP2R5D	0.073	0.087	0.3	63	-10000	0	63
APC	0.024	0.041	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.1	0.22	348	-10000	0	348
CREBBP	0.004	0.017	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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
TGM2	0.004	0.045	-10000	0	-0.5	4	4
GNB1/GNG2	-0.04	0.072	-10000	0	-0.18	102	102
AKT1	-0.006	0.1	-10000	0	-0.21	25	25
EGF	-0.09	0.2	-10000	0	-0.51	99	99
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.011	0.085	-10000	0	-0.42	10	10
mol:Ca2+	-0.026	0.14	-10000	0	-0.3	104	104
LYN	0.028	0.049	-10000	0	-0.36	5	5
RhoA/GTP	-0.027	0.048	-10000	0	-0.14	13	13
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.03	0.16	-10000	0	-0.34	104	104
GNG2	0.008	0.032	-10000	0	-0.5	2	2
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.024	0.041	-10000	0	-0.33	3	3
G beta5/gamma2	-0.052	0.094	-10000	0	-0.23	102	102
PRKCH	-0.032	0.16	-10000	0	-0.34	104	104
DNM1	0.002	0.064	-10000	0	-0.51	8	8
TXA2/TP beta/beta Arrestin3	-0.004	0.018	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.002	0.077	-10000	0	-0.5	12	12
G12 family/GTP	-0.066	0.12	-10000	0	-0.29	104	104
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.008	0.032	-10000	0	-0.5	2	2
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.008	0.096	0.34	11	-10000	0	11
mol:NADP	-0.001	0.074	-10000	0	-0.5	11	11
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.056	0.17	-10000	0	-0.5	66	66
mol:IP3	-0.039	0.18	-10000	0	-0.37	104	104
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.062	0.23	-10000	0	-0.5	104	104
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.012	0.096	-10000	0	-0.36	6	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.018	0.075	-10000	0	-0.41	9	9
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.001	0.067	-10000	0	-0.5	9	9
PRKCB1	-0.039	0.17	-10000	0	-0.37	104	104
GNAQ	0.009	0.022	-10000	0	-0.5	1	1
mol:L-citrulline	-0.001	0.074	-10000	0	-0.5	11	11
TXA2/TXA2-R family	-0.064	0.24	-10000	0	-0.51	104	104
LCK	0.026	0.055	-10000	0	-0.36	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.01	0.051	-10000	0	-0.5	3	3
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.021	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.008	0.048	-10000	0	-0.49	3	3
MAPK14	-0.01	0.11	-10000	0	-0.22	102	102
TGM2/GTP	-0.046	0.19	-10000	0	-0.41	104	104
MAPK11	-0.011	0.11	-10000	0	-0.22	102	102
ARHGEF1	-0.009	0.087	-10000	0	-0.18	58	58
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.039	0.18	-10000	0	-0.38	104	104
RAB11/GDP	0.01	0.001	-10000	0	-10000	0	0
ICAM1	-0.024	0.14	-10000	0	-0.28	102	102
cAMP biosynthetic process	-0.038	0.16	-10000	0	-0.34	104	104
Gq family/GTP/EBP50	0.015	0.046	-10000	0	-0.34	4	4
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.028	0.049	-10000	0	-0.36	5	5
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.006	0.079	-10000	0	-0.32	14	14
VCAM1	-0.026	0.14	-10000	0	-0.29	102	102
TP beta/Gq family/GDP/G beta5/gamma2	0.024	0.041	-10000	0	-0.33	3	3
platelet activation	-0.014	0.15	-10000	0	-0.29	104	104
PGI2/IP	-0.006	0.047	-10000	0	-0.36	9	9
PRKACA	0.005	0.064	-10000	0	-0.3	18	18
Gq family/GDP/G beta5/gamma2	0.022	0.043	-10000	0	-0.28	6	6
TXA2/TP beta/beta Arrestin2	-0.003	0.015	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.012	0.061	-10000	0	-0.28	18	18
mol:DAG	-0.045	0.19	-10000	0	-0.41	104	104
EGFR	-0.006	0.089	-10000	0	-0.5	16	16
TXA2/TP alpha	-0.057	0.22	-10000	0	-0.47	104	104
Gq family/GTP	-0.007	0.048	-10000	0	-0.24	16	16
YES1	0.028	0.049	-10000	0	-0.36	5	5
GNAI2/GTP	-0.009	0.049	-10000	0	-0.42	5	5
PGD2/DP	-0.008	0.054	-10000	0	-0.36	12	12
SLC9A3R1	0.008	0.032	-10000	0	-0.51	2	2
FYN	0.027	0.05	-10000	0	-0.36	5	5
mol:NO	-0.001	0.074	-10000	0	-0.5	11	11
GNA15	0.01	0	-10000	0	-10000	0	0
PGK/cGMP	-0.045	0.11	-10000	0	-0.3	76	76
RhoA/GDP	0.01	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.055	-10000	0	-0.46	5	5
NOS3	-0.001	0.074	-10000	0	-0.5	11	11
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.033	0.16	-10000	0	-0.34	105	105
PRKCB	-0.035	0.17	-10000	0	-0.35	105	105
PRKCE	-0.032	0.16	-10000	0	-0.34	104	104
PRKCD	-0.037	0.17	-10000	0	-0.37	104	104
PRKCG	-0.05	0.19	-10000	0	-0.39	104	104
muscle contraction	-0.057	0.22	-10000	0	-0.48	104	104
PRKCZ	-0.03	0.16	-10000	0	-0.33	104	104
ARR3	-0.001	0.039	-10000	0	-0.51	3	3
TXA2/TP beta	-0.01	0.055	-10000	0	-0.47	5	5
PRKCQ	-0.054	0.18	-10000	0	-0.38	106	106
MAPKKK cascade	-0.054	0.21	-10000	0	-0.45	104	104
SELE	-0.047	0.18	-10000	0	-0.39	102	102
TP beta/GNAI2/GDP/G beta/gamma	-0.009	0.051	-10000	0	-0.47	4	4
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.004	0.083	-10000	0	-0.5	14	14
chemotaxis	-0.078	0.27	-10000	0	-0.6	102	102
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.032	-10000	0	-0.5	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.045	0.11	-10000	0	-0.31	76	76
fibroblast growth factor receptor signaling pathway	-0.045	0.11	-10000	0	-0.3	76	76
LAMA1	-0.017	0.12	-10000	0	-0.51	27	27
PRNP	0.007	0.039	-10000	0	-0.5	3	3
GPC1/SLIT2	-0.094	0.16	-10000	0	-0.36	137	137
SMAD2	0.017	0.049	-10000	0	-0.26	16	16
GPC1/PrPc/Cu2+	-0.003	0.032	-10000	0	-0.3	6	6
GPC1/Laminin alpha1	-0.021	0.086	-10000	0	-0.37	29	29
TDGF1	-0.019	0.12	-10000	0	-0.5	28	28
CRIPTO/GPC1	-0.021	0.085	-10000	0	-0.36	31	31
APP/GPC1	-0.002	0.027	-10000	0	-0.35	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.002	0.075	-10000	0	-0.29	31	31
FLT1	0.01	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.009	0.051	-10000	0	-0.29	16	16
SERPINC1	-0.003	0.075	-10000	0	-0.51	11	11
FYN	0.001	0.078	-10000	0	-0.3	31	31
FGR	-0.021	0.12	-10000	0	-0.32	65	65
positive regulation of MAPKKK cascade	-0.018	0.12	-10000	0	-0.37	35	35
SLIT2	-0.12	0.22	-10000	0	-0.5	135	135
GPC1/NRG	-0.078	0.15	-10000	0	-0.36	112	112
NRG1	-0.1	0.21	-10000	0	-0.5	111	111
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.022	-10000	0	-0.29	3	3
LYN	0.002	0.075	-10000	0	-0.29	31	31
mol:Spermine	0.007	0.028	-10000	0	-0.36	3	3
cell growth	-0.045	0.11	-10000	0	-0.3	76	76
BMP signaling pathway	-0.007	0.039	0.5	3	-10000	0	3
SRC	0.002	0.075	-10000	0	-0.29	31	31
TGFBR1	0.009	0.023	-10000	0	-0.51	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.08	0.19	-10000	0	-0.5	90	90
GPC1	0.007	0.039	-10000	0	-0.5	3	3
TGFBR1 (dimer)	0.009	0.023	-10000	0	-0.51	1	1
VEGFA	0.01	0	-10000	0	-10000	0	0
BLK	-0.053	0.14	-10000	0	-0.3	117	117
HCK	-0.012	0.1	-10000	0	-0.31	52	52
FGF2	-0.063	0.18	-10000	0	-0.5	74	74
FGFR1	0.007	0.039	-10000	0	-0.5	3	3
VEGFR1 homodimer	0.01	0	-10000	0	-10000	0	0
TGFBR2	-0.002	0.077	-10000	0	-0.5	12	12
cell death	-0.002	0.027	-10000	0	-0.35	3	3
ATIII/GPC1	-0.01	0.058	-10000	0	-0.36	14	14
PLA2G2A/GPC1	-0.064	0.14	-10000	0	-0.36	92	92
LCK	0	0.078	-10000	0	-0.29	34	34
neuron differentiation	-0.078	0.15	-10000	0	-0.36	112	112
PrPc/Cu2+	-0.002	0.027	-10000	0	-0.36	3	3
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.002	0.077	-10000	0	-0.5	12	12

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0	-9999	-10000	0	0
CCL5	0.005	0.05	-9999	-0.5	5	5
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.11	-9999	-0.33	34	34
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.1	0.1	-9999	-0.31	37	37
Syndecan-1/Syntenin	-0.1	0.1	-9999	-0.31	34	34
MAPK3	-0.082	0.095	-9999	-0.49	2	2
HGF/MET	-0.044	0.12	-9999	-0.37	62	62
TGFB1/TGF beta receptor Type II	0.01	0	-9999	-10000	0	0
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	-0.1	0.1	-9999	-0.31	37	37
Syndecan-1/RANTES	-0.1	0.1	-9999	-0.32	38	38
Syndecan-1/CD147	-0.092	0.099	-9999	-0.34	8	8
Syndecan-1/Syntenin/PIP2	-0.11	0.086	-9999	-0.3	34	34
LAMA5	0.007	0.039	-9999	-0.5	3	3
positive regulation of cell-cell adhesion	-0.1	0.085	-9999	-0.29	34	34
MMP7	-0.09	0.2	-9999	-0.51	99	99
HGF	-0.021	0.12	-9999	-0.5	31	31
Syndecan-1/CASK	-0.11	0.1	-9999	-0.31	34	34
Syndecan-1/HGF/MET	-0.12	0.13	-9999	-0.4	51	51
regulation of cell adhesion	-0.074	0.092	-9999	-0.63	1	1
HPSE	0.008	0.032	-9999	-0.51	2	2
positive regulation of cell migration	-0.11	0.11	-9999	-0.33	34	34
SDC1	-0.11	0.11	-9999	-0.33	34	34
Syndecan-1/Collagen	-0.11	0.11	-9999	-0.33	34	34
PPIB	0.009	0.023	-9999	-0.51	1	1
MET	-0.024	0.13	-9999	-0.5	34	34
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.1	0.21	-9999	-0.51	112	112
MAPK1	-0.082	0.095	-9999	-0.49	2	2
homophilic cell adhesion	-0.11	0.11	-9999	-0.33	34	34
MMP1	-0.33	0.24	-9999	-0.51	342	342

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.089	0.16	-9999	-0.37	134	134
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.042	0.12	-9999	-0.36	61	61
STXBP1	0.007	0.039	-9999	-0.5	3	3
ACh/CHRNA1	-0.033	0.098	-9999	-0.34	43	43
RAB3GAP2/RIMS1/UNC13B	-0.035	0.095	-9999	-0.29	61	61
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	-0.051	0.16	-9999	-0.5	60	60
mol:ACh	-0.017	0.04	-9999	-0.078	138	138
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.082	0.11	-9999	-0.35	27	27
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.033	0.097	-9999	-0.34	43	43
UNC13B	0.009	0.022	-9999	-0.5	1	1
CHRNA1	-0.033	0.14	-9999	-0.51	43	43
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.037	0.11	-9999	-0.36	49	49
SNAP25	-0.003	0.041	-9999	-0.18	25	25
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.039	0.15	-9999	-0.51	49	49
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.071	0.14	-9999	-0.3	137	137
STX1A/SNAP25 fragment 1/VAMP2	-0.082	0.11	-9999	-0.35	27	27

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.055	-9999	-0.35	13	13
alphaV beta3 Integrin	-0.058	0.12	-9999	-0.3	98	98
PTK2	-0.058	0.15	-9999	-0.43	39	39
IGF1R	0.009	0.022	-9999	-0.5	1	1
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
CDKN1B	-0.1	0.2	-9999	-0.5	88	88
VEGFA	0.01	0	-9999	-10000	0	0
ILK	-0.1	0.2	-9999	-0.5	88	88
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.094	0.18	-9999	-0.47	87	87
PTK2B	0.009	0.077	-9999	-0.49	2	2
alphaV/beta3 Integrin/JAM-A	-0.092	0.15	-9999	-0.51	31	31
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.032	0.092	-9999	-0.3	55	55
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.045	-9999	-0.28	13	13
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.018	0.097	-9999	-0.37	9	9
alphaV/beta3 Integrin/Syndecan-1	-0.016	0.067	-9999	-0.3	28	28
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.05	0.11	-9999	-0.53	11	11
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.22	0.15	-9999	-0.32	365	365
RPS6KB1	-0.01	0.12	-9999	-0.49	11	11
TLN1	0.009	0.022	-9999	-0.5	1	1
MAPK3	-0.096	0.19	-9999	-0.51	77	77
GPR124	0.007	0.039	-9999	-0.5	3	3
MAPK1	-0.096	0.19	-9999	-0.51	77	77
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
alphaV/beta3 Integrin/Tumstatin	-0.095	0.14	-9999	-0.3	161	161
cell adhesion	-0.024	0.069	-9999	-0.28	2	2
ANGPTL3	-0.021	0.12	-9999	-0.51	27	27
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.046	-9999	-0.29	13	13
IGF-1R heterotetramer	0.009	0.022	-9999	-0.5	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.002	0.077	-9999	-0.5	12	12
ITGB3	-0.018	0.12	-9999	-0.51	28	28
IGF1	-0.002	0.077	-9999	-0.5	12	12
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.074	-9999	-0.31	29	29
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.008	0.032	-9999	-0.5	2	2
alphaV/beta3 Integrin/CD47	-0.017	0.069	-9999	-0.3	30	30
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.043	0.11	-9999	-0.31	70	70
CSF1	0.005	0.05	-9999	-0.5	5	5
PIK3C2A	-0.1	0.2	-9999	-0.5	88	88
PI4 Kinase/Pyk2	-0.08	0.13	-9999	-0.44	34	34
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.072	-9999	-0.27	40	40
FAK1/Vinculin	-0.041	0.12	-9999	-0.34	39	39
alphaV beta3/Integrin/ppsTEM5	-0.018	0.075	-9999	-0.32	29	29
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.084	0.2	-9999	-0.5	95	95
BCAR1	0.009	0.022	-9999	-0.5	1	1
FGF2	-0.063	0.18	-9999	-0.5	74	74
F11R	-0.036	0.13	-9999	-0.35	75	75
alphaV/beta3 Integrin/Lactadherin	-0.016	0.067	-9999	-0.3	28	28
alphaV/beta3 Integrin/TGFBR2	-0.023	0.079	-9999	-0.3	40	40
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.028	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.015	0.064	-9999	-0.28	28	28
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.005	0.05	-9999	-0.5	5	5
alphaV/beta3 Integrin/Pyk2	-0.02	0.07	-9999	-0.49	2	2
SDC1	0.01	0	-9999	-10000	0	0
VAV3	0.024	0.045	-9999	-0.49	1	1
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.022	-9999	-0.5	1	1
FAK1/Paxillin	-0.041	0.12	-9999	-0.34	38	38
cell migration	-0.031	0.12	-9999	-0.36	16	16
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.082	0.13	-9999	-0.46	31	31
SPP1	-0.35	0.24	-9999	-0.51	359	359
KDR	-0.003	0.08	-9999	-0.5	13	13
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.13	0.23	-9999	-0.5	139	139
angiogenesis	-0.075	0.21	-9999	-0.51	79	79
Rac1/GTP	-0.005	0.036	-9999	-0.45	1	1
EDIL3	-0.037	0.15	-9999	-0.5	47	47
cell proliferation	-0.023	0.079	-9999	-0.29	40	40

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.039	0.079	-10000	0	-0.29	21	21
NT3 (dimer)/TRKC	-0.086	0.17	-10000	0	-0.39	114	114
NT3 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.32	212	212
SHC/Grb2/SOS1/GAB1/PI3K	0.027	0.021	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.26	0.25	-10000	0	-0.5	269	269
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.01	0.099	-10000	0	-0.5	20	20
NTRK2	-0.18	0.25	-10000	0	-0.5	191	191
NTRK3	-0.089	0.2	-10000	0	-0.5	100	100
NT-4/5 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.33	209	209
neuron apoptosis	0.2	0.2	0.52	110	-10000	0	110
SHC 2-3/Grb2	-0.22	0.22	-10000	0	-0.57	110	110
SHC1	0.008	0.032	-10000	0	-0.51	2	2
SHC2	-0.14	0.14	-10000	0	-0.44	57	57
SHC3	-0.22	0.26	-10000	0	-0.64	119	119
STAT3 (dimer)	0.011	0.04	-10000	0	-0.33	7	7
NT3 (dimer)/TRKA	-0.037	0.11	-10000	0	-0.32	60	60
RIN/GDP	-0.024	0.076	-10000	0	-0.27	6	6
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.008	0.032	-10000	0	-0.51	2	2
DNAJA3	-0.026	0.069	-10000	0	-0.31	11	11
RIN/GTP	-0.002	0.028	-10000	0	-0.37	3	3
CCND1	0.014	0.087	-10000	0	-0.73	7	7
MAGED1	0.009	0.023	-10000	0	-0.51	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.018	0.12	-10000	0	-0.5	28	28
SHC/GRB2/SOS1	-0.001	0.019	-10000	0	-0.3	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.046	0.12	-10000	0	-0.33	71	71
TRKA/NEDD4-2	-0.014	0.068	-10000	0	-0.35	20	20
ELMO1	0.005	0.05	-10000	0	-0.5	5	5
RhoG/GTP/ELMO1/DOCK1	-0.003	0.029	-10000	0	-0.3	5	5
NGF	-0.028	0.14	-10000	0	-0.5	38	38
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.005	0.05	-10000	0	-0.5	5	5
RIT2	-0.002	0.039	-10000	0	-0.51	3	3
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.008	0.032	-10000	0	-0.51	2	2
DNM1	0.002	0.064	-10000	0	-0.51	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.028	0.074	-10000	0	-0.32	14	14
mol:GDP	-0.035	0.11	-10000	0	-0.33	13	13
NGF (dimer)	-0.028	0.13	-10000	0	-0.5	38	38
RhoG/GDP	-0.004	0.035	-10000	0	-0.36	5	5
RIT1/GDP	-0.019	0.074	-10000	0	-0.24	5	5
TIAM1	0	0.07	-10000	0	-0.5	10	10
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
BDNF (dimer)/TRKB	-0.26	0.21	-10000	0	-0.38	347	347
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.001	0.022	-10000	0	-0.36	2	2
FRS2 family/SHP2	-0.002	0.023	-10000	0	-0.3	3	3
SHC/GRB2/SOS1/GAB1	-0.002	0.023	-10000	0	-0.26	4	4
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.018	0.12	-10000	0	-0.5	28	28
RAP1/GDP	-0.031	0.052	-10000	0	-0.24	1	1
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.26	0.25	-10000	0	-0.5	269	269
ubiquitin-dependent protein catabolic process	-0.033	0.094	-10000	0	-0.3	57	57
Schwann cell development	-0.047	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.002	0.02	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.029	0.023	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.24	0.21	-10000	0	-0.5	177	177
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.093	0.075	-10000	0	-0.28	1	1
STAT3	0.011	0.039	-10000	0	-0.32	7	7
axon guidance	-0.23	0.2	-10000	0	-0.48	177	177
MAPK3	-0.018	0.12	-10000	0	-0.3	71	71
MAPK1	-0.018	0.12	-10000	0	-0.3	71	71
CDC42/GDP	-0.019	0.074	-10000	0	-0.24	5	5
NTF3	-0.018	0.12	-10000	0	-0.5	28	28
NTF4	-0.018	0.12	-10000	0	-0.5	28	28
NGF (dimer)/TRKA/FAIM	-0.033	0.095	-10000	0	-0.3	57	57
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
FRS3	0.009	0.023	-10000	0	-0.51	1	1
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.008	0.032	-10000	0	-0.5	2	2
RASGRF1	-0.13	0.14	-10000	0	-0.43	46	46
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.058	0.15	-10000	0	-0.33	117	117
RGS19	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.011	0.065	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.074	-10000	0	-0.24	5	5
NGF (dimer)/TRKA/GRIT	-0.034	0.097	-10000	0	-0.31	57	57
neuron projection morphogenesis	-0.001	0.08	-10000	0	-0.45	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.033	0.095	-10000	0	-0.3	57	57
MAP2K1	0.029	0.024	-10000	0	-10000	0	0
NGFR	-0.007	0.092	-10000	0	-0.5	17	17
NGF (dimer)/TRKA/GIPC/GAIP	0.004	0.07	-10000	0	-0.27	3	3
RAS family/GTP/PI3K	0.023	0.014	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.018	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	3	3
MAPKKK cascade	-0.083	0.16	-10000	0	-0.65	33	33
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.014	0.068	-10000	0	-0.35	20	20
SQSTM1	0.009	0.023	-10000	0	-0.51	1	1
BDNF (dimer)/TRKB/GIPC	-0.23	0.19	-10000	0	-0.34	347	347
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.029	0.081	-10000	0	-0.49	2	2
MATK	-0.013	0.1	-10000	0	-0.5	23	23
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.026	0.049	-10000	0	-0.24	2	2
NGF (dimer)/TRKA	-0.028	0.075	-10000	0	-0.33	11	11
Rac1/GTP	-0.086	0.098	-10000	0	-0.3	49	49
FRS2 family/SHP2/CRK family	-0.001	0.018	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.061	-10000	0	-0.54	5	5
HDAC1	0.002	0.007	-10000	0	-10000	0	0
AES	0.009	0.002	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0.007	0.039	-10000	0	-0.51	3	3
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.009	0.002	-10000	0	-10000	0	0
AP1	-0.028	0.12	-10000	0	-0.29	79	79
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.01	0.056	-10000	0	-0.33	2	2
NICD/RBPSUH	-0.005	0.053	-10000	0	-0.54	5	5
WIF1	-0.34	0.24	-10000	0	-0.5	356	356
NOTCH1	-0.006	0.056	-10000	0	-0.57	5	5
PSENEN	0.009	0.023	-10000	0	-0.51	1	1
KREMEN2	-0.12	0.22	-10000	0	-0.51	128	128
DKK1	-0.12	0.23	-10000	0	-0.5	135	135
beta catenin/beta TrCP1	0.018	0.052	-10000	0	-10000	0	0
APH1B	0.008	0.032	-10000	0	-0.5	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.005	0.026	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.012	0.064	0.27	1	-0.23	1	2
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.017	0.11	-10000	0	-0.5	27	27
JUN	0.007	0.039	-10000	0	-0.5	3	3
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.013	0.055	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.13	0.19	-10000	0	-0.36	194	194
HNF1A	-0.097	0.21	-10000	0	-0.51	105	105
CTBP1	0.009	0.002	-10000	0	-10000	0	0
MYC	0.015	0.084	-10000	0	-1.3	2	2
NKD1	-0.053	0.17	-10000	0	-0.5	63	63
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.007	0.056	-10000	0	-0.54	5	5
apoptosis	-0.028	0.12	-10000	0	-0.29	79	79
Delta 1/NOTCHprecursor	-0.01	0.061	-10000	0	-0.54	5	5
DLL1	0.001	0.067	-10000	0	-0.5	9	9
PPARD	0.02	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.018	-10000	0	-10000	0	0
APC	-0.005	0.026	-10000	0	-0.19	5	5
DVL1	-0.032	0.032	-10000	0	-0.43	2	2
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.35	223	223
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.01	0.006	-10000	0	-10000	0	0
CCND1	0.004	0.15	-10000	0	-1.3	7	7
WNT1	-0.003	0.078	-10000	0	-0.51	12	12
Axin1/APC/beta catenin	0.012	0.04	-10000	0	-0.28	1	1
DKK2	-0.097	0.21	-10000	0	-0.5	108	108
NOTCH1 precursor/DVL1	-0.017	0.054	-10000	0	-0.49	6	6
GSK3B	0.009	0	-10000	0	-10000	0	0
FRAT1	0.009	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.007	0.056	-10000	0	-0.54	5	5
PPP2R5D	0.015	0.085	0.24	63	-10000	0	63
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.12	-10000	0	-0.26	361	361
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.002	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.022	-9999	-0.35	2	2
Necdin/E2F1	-0.01	0.058	-9999	-0.36	14	14
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.029	0.078	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.16	-9999	-0.32	182	182
NT-4/5 (dimer)/p75(NTR)	-0.031	0.1	-9999	-0.38	42	42
IKBKB	0.01	0	-9999	-10000	0	0
AKT1	0.002	0.083	-9999	-10000	0	0
IKBKG	0.01	0	-9999	-10000	0	0
BDNF	-0.26	0.25	-9999	-0.5	269	269
MGDIs/NGR/p75(NTR)/LINGO1	-0.048	0.12	-9999	-0.31	79	79
FURIN	-0.004	0.084	-9999	-0.51	14	14
proBDNF (dimer)/p75(NTR)/Sortilin	-0.16	0.16	-9999	-0.3	278	278
LINGO1	-0.055	0.17	-9999	-0.51	64	64
Sortilin/TRAF6/NRIF	-0.002	0.019	-9999	-10000	0	0
proBDNF (dimer)	-0.26	0.25	-9999	-0.5	269	269
NTRK1	-0.01	0.099	-9999	-0.5	20	20
RTN4R	0.008	0.032	-9999	-0.5	2	2
neuron apoptosis	-0.11	0.14	-9999	-0.41	32	32
IRAK1	0.009	0.023	-9999	-0.51	1	1
SHC1	-0.013	0.099	-9999	-0.29	57	57
ARHGDIA	0.01	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.018	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.029	0.082	-9999	-10000	0	0
MAGEH1	0.01	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.032	0.088	-9999	-0.52	2	2
Mammalian IAPs/DIABLO	-0.004	0.03	-9999	-10000	0	0
proNGF (dimer)	-0.028	0.13	-9999	-0.5	38	38
MAGED1	0.009	0.023	-9999	-0.51	1	1
APP	0.01	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.018	0.12	-9999	-0.5	28	28
ZNF274	0.01	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.026	0.075	-9999	-10000	0	0
NGF	-0.028	0.14	-9999	-0.5	38	38
cell cycle arrest	0.01	0.11	-9999	-0.28	24	24
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.062	-9999	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.088	-9999	-0.31	42	42
NCSTN	0.01	0	-9999	-10000	0	0
mol:GTP	-0.032	0.092	-9999	-0.29	56	56
PSENEN	0.009	0.023	-9999	-0.51	1	1
mol:ceramide	-0.005	0.089	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.015	0.056	-9999	-0.39	1	1
p75(NTR)/beta APP	-0.012	0.064	-9999	-0.36	17	17
BEX1	-0.14	0.23	-9999	-0.5	146	146
mol:GDP	-0.02	0.097	-9999	-0.3	55	55
NGF (dimer)	-0.084	0.14	-9999	-0.28	152	152
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.042	0.1	-9999	-0.53	4	4
PIK3R1	0.009	0.022	-9999	-0.5	1	1
RAC1/GTP	-0.027	0.077	-9999	-0.25	55	55
MYD88	0.01	0	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.032	0.092	-9999	-0.3	56	56
RHOB	0.009	0.022	-9999	-0.5	1	1
RHOA	0.01	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.006	0.044	-9999	-0.36	8	8
NT3 (dimer)	-0.018	0.12	-9999	-0.5	28	28
TP53	-0.11	0.14	-9999	-0.46	10	10
PRDM4	-0.005	0.09	-9999	-10000	0	0
BDNF (dimer)	-0.3	0.22	-9999	-0.39	392	392
PIK3CA	0.01	0	-9999	-10000	0	0
SORT1	0.008	0.032	-9999	-0.5	2	2
activation of caspase activity	-0.028	0.077	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.029	0.082	-9999	-10000	0	0
RHOC	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
MAPK10	-0.098	0.15	-9999	-0.41	54	54
DIABLO	0.01	0	-9999	-10000	0	0
SMPD2	-0.005	0.09	-9999	-10000	0	0
APH1B	0.008	0.032	-9999	-0.5	2	2
APH1A	0.01	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.033	0.093	-9999	-0.3	57	57
PSEN1	0.01	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.031	0.11	-9999	-0.38	41	41
MAPK8	-0.075	0.12	-9999	-0.37	30	30
MAPK9	-0.075	0.12	-9999	-0.37	30	30
APAF1	0.01	0	-9999	-10000	0	0
NTF3	-0.018	0.12	-9999	-0.5	28	28
NTF4	-0.018	0.12	-9999	-0.5	28	28
NDN	0.004	0.055	-9999	-0.5	6	6
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.024	0.068	-9999	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.016	-9999	-0.26	2	2
RhoA-B-C/GTP	-0.032	0.091	-9999	-0.29	56	56
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.13	0.13	-9999	-0.49	10	10
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.14	0.14	-9999	-0.52	10	10
PRKACB	0.009	0.023	-9999	-0.51	1	1
proBDNF (dimer)/p75 ECD	-0.18	0.18	-9999	-0.35	269	269
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0.003	0.06	-9999	-0.51	7	7
BIRC2	0.01	0	-9999	-10000	0	0
neuron projection morphogenesis	0.018	0.11	-9999	-0.37	1	1
BAD	-0.077	0.13	-9999	-0.41	25	25
RIPK2	0.01	0	-9999	-10000	0	0
NGFR	-0.007	0.092	-9999	-0.5	17	17
CYCS	0.001	0.086	-9999	-0.49	1	1
ADAM17	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.028	0.081	-9999	-10000	0	0
BCL2L11	-0.077	0.13	-9999	-0.41	25	25
BDNF (dimer)/p75(NTR)	-0.2	0.18	-9999	-0.36	278	278
PI3K	-0.028	0.081	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.029	0.082	-9999	-0.26	57	57
NDNL2	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
PRKCI	0.01	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.038	0.11	-9999	-0.36	55	55
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.029	0.084	-9999	-0.53	1	1
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
PRKCZ	0.007	0.039	-9999	-0.5	3	3
PLG	-0.009	0.074	-9999	-0.51	11	11
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.14	0.16	-9999	-0.47	36	36
SQSTM1	0.009	0.023	-9999	-0.51	1	1
NGFRAP1	0.005	0.05	-9999	-0.5	5	5
CASP3	-0.071	0.12	-9999	-0.38	25	25
E2F1	0.002	0.064	-9999	-0.51	8	8
CASP9	0.01	0	-9999	-10000	0	0
IKK complex	-0.025	0.067	-9999	-0.39	3	3
NGF (dimer)/TRKA	-0.04	0.11	-9999	-0.36	57	57
MMP7	-0.09	0.2	-9999	-0.51	99	99
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.026	0.075	-9999	-10000	0	0
MMP3	-0.19	0.25	-9999	-0.51	195	195
APAF-1/Caspase 9	-0.021	0.057	-9999	-0.37	2	2

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.002	0.063	-10000	0	-0.5	8	8
EPHB2	-0.046	0.16	-10000	0	-0.51	56	56
EFNB1	0.01	0.054	-10000	0	-0.36	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.058	0.12	-10000	0	-0.48	17	17
Ephrin B2/EPHB1-2	-0.062	0.13	-10000	0	-0.29	113	113
neuron projection morphogenesis	-0.056	0.11	-10000	0	-0.46	17	17
Ephrin B1/EPHB1-2/Tiam1	-0.059	0.13	-10000	0	-0.52	17	17
DNM1	0.002	0.064	-10000	0	-0.51	8	8
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.046	0.18	-10000	0	-0.58	54	54
YES1	-0.083	0.25	-10000	0	-0.8	54	54
Ephrin B1/EPHB1-2/NCK2	-0.054	0.12	-10000	0	-0.49	14	14
PI3K	-0.047	0.19	-10000	0	-0.58	54	54
mol:GDP	-0.059	0.13	-10000	0	-0.51	17	17
ITGA2B	-0.044	0.16	-10000	0	-0.5	54	54
endothelial cell proliferation	-0.004	0.037	-10000	0	-0.3	8	8
FYN	-0.083	0.25	-10000	0	-0.8	54	54
MAP3K7	-0.064	0.19	-10000	0	-0.62	54	54
FGR	-0.095	0.25	-10000	0	-0.82	54	54
TIAM1	0	0.07	-10000	0	-0.5	10	10
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.071	0.2	-10000	0	-0.58	54	54
LYN	-0.083	0.25	-10000	0	-0.8	54	54
Ephrin B1/EPHB1-2/Src Family Kinases	-0.078	0.23	-10000	0	-0.74	54	54
Ephrin B1/EPHB1-2	-0.073	0.21	-10000	0	-0.67	54	54
SRC	-0.083	0.24	-10000	0	-0.8	54	54
ITGB3	-0.018	0.12	-10000	0	-0.51	28	28
EPHB1	-0.051	0.17	-10000	0	-0.51	60	60
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.004	0.037	-10000	0	-0.3	8	8
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	81	81
BLK	-0.088	0.25	-10000	0	-0.8	54	54
HCK	-0.089	0.25	-10000	0	-0.82	54	54
regulation of stress fiber formation	0.054	0.12	0.49	14	-10000	0	14
MAPK8	-0.038	0.18	-10000	0	-0.55	54	54
Ephrin B1/EPHB1-2/RGS3	-0.054	0.12	-10000	0	-0.49	14	14
endothelial cell migration	-0.055	0.17	-10000	0	-0.52	56	56
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.058	0.19	-10000	0	-0.61	54	54
regulation of focal adhesion formation	0.054	0.12	0.49	14	-10000	0	14
chemotaxis	0.054	0.12	0.49	14	-10000	0	14
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	-0.057	0.12	-10000	0	-0.48	17	17
angiogenesis	-0.072	0.2	-10000	0	-0.66	54	54
LCK	-0.083	0.25	-10000	0	-0.8	54	54

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.13	0.4	-10000	0	-1.1	49	49
IL23A	-0.15	0.43	-10000	0	-1.2	45	45
NF kappa B1 p50/RelA/I kappa B alpha	-0.21	0.35	-10000	0	-1.1	52	52
positive regulation of T cell mediated cytotoxicity	-0.15	0.45	-10000	0	-1.2	54	54
ITGA3	-0.14	0.4	-10000	0	-1.1	51	51
IL17F	-0.07	0.28	-10000	0	-0.69	45	45
IL12B	0.01	0.064	-10000	0	-0.53	6	6
STAT1 (dimer)	-0.14	0.43	-10000	0	-1.2	51	51
CD4	-0.13	0.4	-10000	0	-1.1	47	47
IL23	-0.15	0.41	-10000	0	-1.1	46	46
IL23R	-0.001	0.083	-10000	0	-10000	0	0
IL1B	-0.16	0.46	-10000	0	-1.3	52	52
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.12	0.39	-10000	0	-1.1	48	48
TYK2	0.01	0.019	-10000	0	-10000	0	0
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
IL18RAP	-0.01	0.098	-10000	0	-0.5	20	20
IL12RB1	-0.005	0.093	-10000	0	-0.53	15	15
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.001	0.071	-10000	0	-0.39	15	15
IL23R/JAK2	0.001	0.1	-10000	0	-0.42	1	1
positive regulation of chronic inflammatory response	-0.15	0.45	-10000	0	-1.2	54	54
natural killer cell activation	0.001	0.007	0.034	2	-10000	0	2
JAK2	0.015	0.041	-10000	0	-0.52	2	2
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
NFKB1	0.009	0.003	-10000	0	-10000	0	0
RELA	0.009	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.15	0.39	-10000	0	-1	49	49
ALOX12B	-0.14	0.4	-10000	0	-1.1	51	51
CXCL1	-0.14	0.43	-10000	0	-1.2	53	53
T cell proliferation	-0.15	0.45	-10000	0	-1.2	54	54
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.049	0.23	-10000	0	-0.56	32	32
PI3K	-0.21	0.36	-10000	0	-1.1	54	54
IFNG	-0.007	0.033	-10000	0	-0.12	14	14
STAT3 (dimer)	-0.2	0.34	-10000	0	-1	50	50
IL18R1	-0.013	0.1	-10000	0	-0.5	23	23
IL23/IL23R/JAK2/TYK2/SOCS3	-0.06	0.25	-10000	0	-0.66	34	34
IL18/IL18R	-0.017	0.11	-10000	0	-0.35	43	43
macrophage activation	-0.013	0.016	-10000	0	-0.044	42	42
TNF	-0.15	0.44	-10000	0	-1.2	50	50
STAT3/STAT4	-0.21	0.36	-10000	0	-1	58	58
STAT4 (dimer)	-0.14	0.43	-10000	0	-1.2	51	51
IL18	0	0.07	-10000	0	-0.5	10	10
IL19	-0.13	0.39	-10000	0	-1.1	48	48
STAT5A (dimer)	-0.14	0.43	-10000	0	-1.2	51	51
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.006	0.045	-10000	0	-0.5	4	4
CXCL9	-0.15	0.42	-10000	0	-1.1	55	55
MPO	-0.14	0.42	-10000	0	-1.1	55	55
positive regulation of humoral immune response	-0.15	0.45	-10000	0	-1.2	54	54
IL23/IL23R/JAK2/TYK2	-0.16	0.48	-10000	0	-1.3	54	54
IL6	-0.28	0.58	-10000	0	-1.2	133	133
STAT5A	0.009	0.022	-10000	0	-0.5	1	1
IL2	0.007	0.009	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.007	0.034	2	-10000	0	2
CD3E	-0.13	0.4	-10000	0	-1.1	51	51
keratinocyte proliferation	-0.15	0.45	-10000	0	-1.2	54	54
NOS2	-0.18	0.48	-10000	0	-1.1	81	81

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.064	0.19	-10000	0	-0.52	75	75
NFATC2	0.003	0.17	-10000	0	-0.63	19	19
NFATC3	-0.011	0.082	-10000	0	-0.3	9	9
CD40LG	-0.074	0.36	-10000	0	-0.96	56	56
ITCH	-0.011	0.099	-10000	0	-10000	0	0
CBLB	-0.011	0.099	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.23	-10000	0	-0.87	28	28
JUNB	0.007	0.039	-10000	0	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.051	0.11	-10000	0	-10000	0	0
T cell anergy	-0.061	0.16	-10000	0	-0.38	98	98
TLE4	0.019	0.15	-10000	0	-0.7	12	12
Jun/NFAT1-c-4/p21SNFT	-0.12	0.31	-10000	0	-0.93	54	54
AP-1/NFAT1-c-4	-0.086	0.41	-10000	0	-1.1	54	54
IKZF1	0.019	0.15	-10000	0	-0.74	11	11
T-helper 2 cell differentiation	0.005	0.19	-10000	0	-0.84	13	13
AP-1/NFAT1	-0.046	0.12	-10000	0	-0.48	21	21
CALM1	-0.011	0.066	-10000	0	-10000	0	0
EGR2	-0.058	0.4	-10000	0	-1.4	32	32
EGR3	-0.1	0.48	-10000	0	-1.4	60	60
NFAT1/FOXP3	-0.043	0.18	-10000	0	-0.5	26	26
EGR1	-0.017	0.12	-10000	0	-0.5	28	28
JUN	0.005	0.042	-10000	0	-0.5	3	3
EGR4	-0.044	0.16	-10000	0	-0.51	53	53
mol:Ca2+	-0.022	0.07	-10000	0	-10000	0	0
GBP3	0.007	0.18	-10000	0	-0.67	25	25
FOSL1	-0.011	0.1	-10000	0	-0.51	21	21
NFAT1-c-4/MAF/IRF4	-0.12	0.3	-10000	0	-0.89	56	56
DGKA	0.024	0.12	-10000	0	-0.6	8	8
CREM	0.009	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.15	0.34	-10000	0	-0.94	66	66
CTLA4	-0.028	0.16	-10000	0	-0.61	15	15
NFAT1-c-4 (dimer)/EGR1	-0.12	0.34	-10000	0	-0.94	65	65
NFAT1-c-4 (dimer)/EGR4	-0.14	0.32	-10000	0	-0.9	64	64
FOS	-0.019	0.12	-10000	0	-0.51	27	27
IFNG	-0.091	0.23	-10000	0	-0.9	27	27
T cell activation	0.009	0.2	-10000	0	-0.68	18	18
MAF	0.009	0.022	-10000	0	-0.5	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.036	0.29	0.77	51	-10000	0	51
TNF	-0.075	0.34	-10000	0	-0.93	56	56
FASLG	-0.12	0.49	-10000	0	-1.3	68	68
TBX21	-0.013	0.1	-10000	0	-0.5	22	22
BATF3	0.01	0	-10000	0	-10000	0	0
PRKCQ	-0.061	0.18	-10000	0	-0.5	74	74
PTPN1	0.025	0.12	-10000	0	-0.6	8	8
NFAT1-c-4/ICER1	-0.12	0.31	-10000	0	-0.88	64	64
GATA3	0.008	0.039	-10000	0	-0.5	3	3
T-helper 1 cell differentiation	-0.053	0.24	-10000	0	-0.88	27	27
IL2RA	-0.12	0.22	-10000	0	-0.81	28	28
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.025	0.12	-10000	0	-0.6	8	8
E2F1	0.006	0.064	-10000	0	-0.5	8	8
PPARG	-0.06	0.18	-10000	0	-0.5	71	71
SLC3A2	0.025	0.12	-10000	0	-0.55	10	10
IRF4	-0.006	0.09	-10000	0	-0.51	16	16
PTGS2	-0.088	0.38	-10000	0	-0.99	59	59
CSF2	-0.085	0.37	-10000	0	-0.97	57	57
JunB/Fra1/NFAT1-c-4	-0.12	0.3	-10000	0	-0.9	57	57
IL4	0.003	0.2	-10000	0	-0.92	12	12
IL5	-0.068	0.34	-10000	0	-0.93	54	54
IL2	0.009	0.2	-10000	0	-0.7	18	18
IL3	-0.026	0.047	-10000	0	-10000	0	0
RNF128	-0.08	0.24	-10000	0	-0.57	98	98
NFATC1	-0.036	0.29	-10000	0	-0.78	51	51
CDK4	0.011	0.17	0.62	12	-10000	0	12
PTPRK	0.025	0.12	-10000	0	-0.71	5	5
IL8	-0.073	0.35	-10000	0	-0.92	55	55
POU2F1	0.01	0.001	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.073	0.14	-10000	0	-0.41	47	47
epithelial cell differentiation	-0.077	0.12	-10000	0	-0.44	22	22
ITCH	0.023	0.018	-10000	0	-10000	0	0
WWP1	-0.019	0.068	-10000	0	-10000	0	0
FYN	0.009	0.022	-10000	0	-0.5	1	1
EGFR	-0.006	0.089	-10000	0	-0.5	16	16
PRL	-0.01	0.08	-10000	0	-0.51	13	13
neuron projection morphogenesis	-0.029	0.11	-10000	0	-0.44	2	2
PTPRZ1	-0.11	0.22	-10000	0	-0.5	117	117
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.069	0.1	-10000	0	-0.49	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.07	0.14	-10000	0	-0.36	54	54
ADAM17	0.023	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.033	0.088	-10000	0	-0.38	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.14	0.17	-10000	0	-0.41	89	89
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.079	0.12	-10000	0	-0.34	54	54
GRIN2B	-0.06	0.13	-10000	0	-0.5	5	5
ErbB4/ErbB2/betacellulin	-0.034	0.062	-10000	0	-0.34	12	12
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	-0.076	0.19	-10000	0	-0.5	87	87
PRLR	-0.052	0.17	-10000	0	-0.5	62	62
E4ICDs/ETO2	-0.042	0.11	-10000	0	-0.42	19	19
axon guidance	0	0.076	-10000	0	-10000	0	0
NEDD4	0.022	0.028	-10000	0	-0.48	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.053	0.13	-10000	0	-0.37	74	74
CBFA2T3	-0.022	0.12	-10000	0	-0.5	32	32
ErbB4/ErbB2/HBEGF	-0.069	0.11	-10000	0	-0.34	49	49
MAPK3	-0.036	0.12	-10000	0	-0.46	2	2
STAT1 (dimer)	-0.024	0.074	-10000	0	-0.32	1	1
MAPK1	-0.036	0.12	-10000	0	-0.46	2	2
JAK2	0.008	0.032	-10000	0	-0.5	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.08	0.12	-10000	0	-0.34	57	57
NRG1	-0.056	0.16	-10000	0	-0.35	111	111
NRG3	-0.19	0.25	-10000	0	-0.5	202	202
NRG2	-0.049	0.16	-10000	0	-0.5	59	59
NRG4	-0.037	0.15	-10000	0	-0.51	46	46
heart development	0	0.076	-10000	0	-10000	0	0
neural crest cell migration	-0.079	0.12	-10000	0	-0.34	57	57
ERBB2	0.024	0.031	-10000	0	-0.36	3	3
WWOX/E4ICDs	-0.024	0.074	-10000	0	-0.33	1	1
SHC1	0.008	0.032	-10000	0	-0.51	2	2
ErbB4/EGFR/neuregulin 4	-0.068	0.11	-10000	0	-0.4	30	30
apoptosis	0.21	0.23	0.45	201	-10000	0	201
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.058	0.12	-10000	0	-0.4	32	32
ErbB4/ErbB2/epiregulin	-0.1	0.13	-10000	0	-0.34	72	72
ErbB4/ErbB4/betacellulin/betacellulin	-0.032	0.092	-10000	0	-0.4	11	11
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.1	0.14	-10000	0	-0.47	32	32
MDM2	-0.022	0.077	-10000	0	-0.33	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.072	0.11	-10000	0	-0.32	54	54
STAT5A	0.005	0.073	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.086	0.13	-10000	0	-0.37	59	59
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.022	-10000	0	-0.36	2	2
E4ICDs/TAB2/NCoR1	-0.039	0.055	-10000	0	-0.3	1	1
STAT5A (dimer)	-0.082	0.13	-10000	0	-0.47	21	21
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.004	0.069	-10000	0	-10000	0	0
LRIG1	0.007	0.039	-10000	0	-0.5	3	3
EREG	-0.15	0.24	-10000	0	-0.5	163	163
BTC	-0.004	0.083	-10000	0	-0.5	14	14
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.003	0.075	-10000	0	-10000	0	0
ERBB4	-0.033	0.088	-10000	0	-0.38	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.001	0.024	-10000	0	-0.53	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.049	0.086	-10000	0	-0.34	16	16
glial cell differentiation	0.039	0.055	0.3	1	-10000	0	1
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.071	0.16	-10000	0	-0.46	38	38

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.011	0.067	-9999	-0.3	2	2
BIRC5	-0.29	0.26	-9999	-0.51	297	297
NFKBIA	-0.008	0.065	-9999	-10000	0	0
CPEB1	-0.064	0.18	-9999	-0.5	74	74
AKT1	-0.008	0.065	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.017	0.061	-9999	-0.36	3	3
NDEL1/TACC3	-0.012	0.057	-9999	-0.38	3	3
GADD45A	0.008	0.032	-9999	-0.5	2	2
GSK3B	0.011	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.01	0.065	-9999	-10000	0	0
MDM2	0.008	0.032	-9999	-0.51	2	2
JUB	0.008	0.032	-9999	-0.5	2	2
TPX2	-0.19	0.19	-9999	-0.36	280	280
TP53	0.002	0.043	-9999	-10000	0	0
DLG7	-0.016	0.065	-9999	-10000	0	0
AURKAIP1	0.009	0.022	-9999	-0.5	1	1
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.013	0.062	-9999	-0.4	3	3
G2/M transition of mitotic cell cycle	-0.017	0.061	-9999	-0.36	3	3
AURKA	-0.018	0.08	-9999	-10000	0	0
AURKB	-0.054	0.052	-9999	-0.13	91	91
CDC25B	-0.011	0.052	-9999	-0.22	1	1
G2/M transition checkpoint	-0.016	0.058	-9999	-0.33	2	2
mRNA polyadenylation	-0.055	0.12	-9999	-0.3	74	74
Aurora A/CPEB	-0.055	0.12	-9999	-0.31	74	74
Aurora A/TACC1/TRAP/chTOG	-0.018	0.075	-9999	-0.36	7	7
BRCA1	0.007	0.039	-9999	-0.51	3	3
centrosome duplication	-0.01	0.065	-9999	-10000	0	0
regulation of centrosome cycle	-0.013	0.057	-9999	-0.37	3	3
spindle assembly	-0.019	0.074	-9999	-0.36	7	7
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.16	0.14	-9999	-0.36	95	95
CENPA	-0.05	0.05	-9999	-0.14	91	91
Aurora A/PP2A	-0.01	0.065	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.005	0.049	-9999	-10000	0	0
negative regulation of DNA binding	0.002	0.043	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.016	0.059	-9999	-0.33	2	2
mitotic prometaphase	0.015	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.018	0.08	-9999	-10000	0	0
TACC1	-0.013	0.1	-9999	-0.5	23	23
TACC3	0.007	0.039	-9999	-0.51	3	3
Aurora A/Antizyme1	-0.012	0.056	-9999	-0.26	1	1
Aurora A/RasGAP	-0.01	0.065	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.009	0.023	-9999	-0.51	1	1
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.003	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.19	0.19	-9999	-0.36	280	280
PPP2R5D	0.01	0	-9999	-10000	0	0
Aurora A/TPX2	-0.16	0.17	-9999	-0.31	280	280
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.22	-10000	0	-0.67	17	17
CRP	-0.15	0.23	-10000	0	-0.63	25	25
cell cycle arrest	-0.17	0.25	-10000	0	-0.57	90	90
TIMP1	-0.12	0.19	-10000	0	-0.62	13	13
IL6ST	-0.014	0.1	-10000	0	-0.5	21	21
Rac1/GDP	-0.07	0.15	-10000	0	-0.44	27	27
AP1	0.003	0.088	-10000	0	-0.54	4	4
GAB2	0.007	0.05	-10000	0	-0.5	5	5
TNFSF11	-0.19	0.25	-10000	0	-0.65	47	47
HSP90B1	-0.005	0.044	-10000	0	-10000	0	0
GAB1	0.009	0.032	-10000	0	-0.5	2	2
MAPK14	-0.047	0.14	-10000	0	-0.54	18	18
AKT1	0.036	0.033	-10000	0	-10000	0	0
FOXO1	0.04	0.033	-10000	0	-10000	0	0
MAP2K6	-0.065	0.15	-10000	0	-0.5	21	21
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.083	0.16	-10000	0	-0.48	25	25
MITF	-0.073	0.15	-10000	0	-0.36	69	69
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	-0.086	0.35	-10000	0	-1.3	41	41
CEBPB	0.015	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.011	0.083	0.22	2	-0.47	5	7
STAT3	-0.17	0.26	-10000	0	-0.61	82	82
STAT1	-0.003	0.012	-10000	0	-10000	0	0
CEBPD	-0.15	0.23	-10000	0	-0.76	15	15
PIK3CA	0.011	0	-10000	0	-10000	0	0
PI3K	0.015	0.017	-10000	0	-0.35	1	1
JUN	0.007	0.039	-10000	0	-0.5	3	3
PIAS3/MITF	-0.062	0.14	-10000	0	-0.48	21	21
MAPK11	-0.048	0.14	-10000	0	-0.55	19	19
STAT3 (dimer)/FOXO1	-0.12	0.24	-10000	0	-0.63	37	37
GRB2/SOS1/GAB family	-0.061	0.12	0.18	2	-0.44	25	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.068	0.16	-10000	0	-0.35	85	85
GRB2	0.011	0.004	-10000	0	-10000	0	0
JAK2	0.008	0.032	-10000	0	-0.5	2	2
LBP	-0.13	0.2	-10000	0	-0.56	25	25
PIK3R1	0.01	0.022	-10000	0	-0.5	1	1
JAK1	0.009	0.004	-10000	0	-10000	0	0
MYC	-0.14	0.23	-10000	0	-0.7	17	17
FGG	-0.33	0.46	-10000	0	-0.98	157	157
macrophage differentiation	-0.17	0.25	-10000	0	-0.57	90	90
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.074	0.13	-10000	0	-0.46	15	15
JUNB	-0.14	0.22	-10000	0	-0.7	18	18
FOS	-0.017	0.11	-10000	0	-0.5	27	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.079	0.15	-10000	0	-0.35	78	78
STAT1/PIAS1	-0.082	0.14	-10000	0	-0.36	67	67
GRB2/SOS1/GAB family/SHP2/PI3K	0.017	0.037	-10000	0	-0.26	2	2
STAT3 (dimer)	-0.17	0.26	-10000	0	-0.59	90	90
PRKCD	-0.098	0.19	-10000	0	-0.54	22	22
IL6R	-0.002	0.074	-10000	0	-0.5	11	11
SOCS3	-0.036	0.16	-10000	0	-0.82	9	9
gp130 (dimer)/JAK1/JAK1/LMO4	-0.001	0.065	-10000	0	-0.29	22	22
Rac1/GTP	-0.084	0.15	-10000	0	-0.37	66	66
HCK	-0.014	0.11	-10000	0	-0.5	24	24
MAPKKK cascade	0.008	0.081	-10000	0	-0.56	5	5
bone resorption	-0.18	0.24	-10000	0	-0.61	48	48
IRF1	-0.14	0.22	-10000	0	-0.67	17	17
mol:GDP	-0.073	0.15	-10000	0	-0.36	69	69
SOS1	0.012	0.006	-10000	0	-10000	0	0
VAV1	-0.075	0.15	-10000	0	-0.36	69	69
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.043	0.14	-10000	0	-0.5	23	23
PTPN11	-0.001	0.01	-10000	0	-10000	0	0
IL6/IL6RA	-0.084	0.16	-10000	0	-0.36	128	128
gp130 (dimer)/TYK2/TYK2/LMO4	-0.003	0.063	-10000	0	-0.29	22	22
gp130 (dimer)/JAK2/JAK2/LMO4	-0.004	0.066	-10000	0	-0.29	24	24
IL6	-0.11	0.22	-10000	0	-0.5	120	120
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.012	0.033	-10000	0	-0.49	2	2
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.009	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.069	0.14	-10000	0	-0.3	97	97
LMO4	0.006	0.024	-10000	0	-0.5	1	1
STAT3 (dimer)/PIAS3	-0.2	0.22	-10000	0	-0.59	68	68
MCL1	0.041	0.03	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin 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
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.006	0.089	-9999	-0.5	16	16
EGF/EGFR	-0.088	0.14	-9999	-0.49	24	24
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.055	0.11	-9999	-0.49	4	4
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.008	0.032	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.09	0.2	-9999	-0.51	99	99
EGF/EGFR dimer/SHC	-0.067	0.13	-9999	-0.31	113	113
mol:GDP	-0.054	0.1	-9999	-0.49	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.064	0.18	-9999	-0.5	75	75
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.049	0.095	-9999	-0.45	4	4
SHC1	0.008	0.032	-9999	-0.51	2	2
HRAS/GDP	-0.05	0.097	-9999	-0.46	4	4
FRAP1	-0.029	0.11	-9999	-0.47	4	4
EGF/EGFR dimer	-0.08	0.15	-9999	-0.37	111	111
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.053	0.13	-9999	-0.35	77	77

×

PDGFR-alpha signaling 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
PDGFRA	0.005	0.045	-9999	-0.5	4	4
PDGF/PDGFRA/CRKL	-0.003	0.03	-9999	-0.34	4	4
positive regulation of JUN kinase activity	-0.003	0.027	-9999	-0.26	2	2
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.079	0.15	-9999	-0.36	112	112
AP1	-0.048	0.19	-9999	-0.87	27	27
mol:IP3	0.015	0.035	-9999	-0.35	4	4
PLCG1	0.015	0.035	-9999	-0.35	4	4
PDGF/PDGFRA/alphaV Integrin	-0.003	0.03	-9999	-0.34	4	4
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.015	0.035	-9999	-0.35	4	4
CAV3	-0.1	0.2	-9999	-0.5	108	108
CAV1	-0.31	0.25	-9999	-0.5	326	326
SHC/Grb2/SOS1	-0.003	0.027	-9999	-0.26	2	2
PDGF/PDGFRA/Shf	-0.004	0.037	-9999	-0.35	6	6
FOS	-0.013	0.2	-9999	-0.86	27	27
JUN	-0.005	0.03	-9999	-0.36	3	3
oligodendrocyte development	-0.003	0.03	-9999	-0.34	4	4
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
mol:DAG	0.015	0.035	-9999	-0.35	4	4
PDGF/PDGFRA	0.005	0.045	-9999	-0.5	4	4
actin cytoskeleton reorganization	-0.004	0.034	-9999	-0.35	5	5
SRF	0.017	0.006	-9999	-10000	0	0
SHC1	0.008	0.032	-9999	-0.51	2	2
PI3K	-0.003	0.028	-9999	-0.28	5	5
PDGF/PDGFRA/Crk/C3G	-0.002	0.024	-9999	-0.28	4	4
JAK1	0.015	0.032	-9999	-0.34	4	4
ELK1/SRF	0.027	0.027	-9999	-10000	0	0
SHB	0.009	0.022	-9999	-0.5	1	1
SHF	0.008	0.032	-9999	-0.51	2	2
CSNK2A1	0.003	0.012	-9999	-10000	0	0
GO:0007205	0.015	0.038	-9999	-0.37	4	4
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.003	0.027	-9999	-0.26	2	2
PDGF/PDGFRA/SHB	-0.004	0.034	-9999	-0.35	5	5
PDGF/PDGFRA/Caveolin-1	-0.23	0.18	-9999	-0.36	327	327
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	0.019	0.038	-9999	-0.32	4	4
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.003	0.03	-9999	-0.34	4	4
JAK-STAT cascade	0.015	0.032	-9999	-0.34	4	4
cell proliferation	-0.004	0.037	-9999	-0.35	6	6

×

Reelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.011	0.062	-9999	-0.36	16	16
VLDLR	-0.002	0.077	-9999	-0.5	12	12
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.009	0.022	-9999	-0.5	1	1
ITGA3	0.005	0.05	-9999	-0.5	5	5
RELN/VLDLR/Fyn	-0.052	0.12	-9999	-0.31	86	86
MAPK8IP1/MKK7/MAP3K11/JNK1	0	0.01	-9999	-10000	0	0
AKT1	-0.016	0.098	-9999	-0.39	9	9
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.51	9	9
RELN/LRP8/DAB1	-0.053	0.11	-9999	-0.28	96	96
LRPAP1/LRP8	-0.009	0.056	-9999	-0.36	13	13
RELN/LRP8/DAB1/Fyn	-0.049	0.1	-9999	-0.27	67	67
DAB1/alpha3/beta1 Integrin	-0.049	0.1	-9999	-0.47	12	12
long-term memory	-0.096	0.14	-9999	-0.5	29	29
DAB1/LIS1	-0.049	0.11	-9999	-0.49	10	10
DAB1/CRLK/C3G	-0.047	0.1	-9999	-0.48	10	10
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	-0.05	0.11	-9999	-0.49	10	10
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.092	0.2	-9999	-0.5	101	101
CDK5R1	-0.006	0.09	-9999	-0.51	16	16
RELN	-0.069	0.18	-9999	-0.5	79	79
PIK3R1	0.009	0.022	-9999	-0.5	1	1
RELN/LRP8/Fyn	-0.053	0.11	-9999	-0.3	92	92
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.096	0.14	-9999	-0.52	25	25
MAPK8	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.052	0.12	-9999	-0.29	91	91
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.034	0.13	-9999	-0.49	13	13
RELN/LRP8	-0.052	0.11	-9999	-0.3	91	91
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.053	0.11	-9999	-0.5	10	10
PI3K	-0.001	0.016	-9999	-0.35	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.035	-9999	-0.35	5	5
RAP1A	-0.009	0.11	-9999	-0.44	10	10
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	0.01	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.008	0.07	-9999	-0.51	10	10
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.001	0.071	-9999	-0.26	3	3
neuron adhesion	0	0.11	-9999	-0.41	12	12
LRP8	-0.003	0.081	-9999	-0.51	13	13
GSK3B	-0.009	0.093	-9999	-0.39	8	8
RELN/VLDLR/DAB1/Fyn	-0.048	0.11	-9999	-0.27	92	92
MAP3K11	0.009	0.022	-9999	-0.5	1	1
RELN/VLDLR/DAB1/P13K	-0.024	0.1	-9999	-0.25	80	80
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.017	0.11	-9999	-0.46	28	28
neuron migration	-0.011	0.13	-9999	-0.45	10	10
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0	0.071	-9999	-0.26	3	3
RELN/VLDLR	-0.052	0.11	-9999	-0.28	97	97

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.029	0.073	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.008	0.043	-9999	-0.25	16	16
POMC	-0.014	0.11	-9999	-0.5	24	24
EGFR	-0.006	0.089	-9999	-0.5	16	16
Syndecan-3/EGFR	-0.008	0.042	-9999	-0.24	16	16
AGRP	-0.21	0.25	-9999	-0.5	219	219
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.009	0.023	-9999	-0.51	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.008	0.032	-9999	-0.5	2	2
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.01	0.089	-9999	-0.51	16	16
long-term memory	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/IL8	-0.01	0.047	-9999	-0.24	20	20
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.009	0.022	-9999	-0.5	1	1
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.03	0.13	-9999	-0.51	37	37
SRC	0.01	0	-9999	-10000	0	0
PTN	-0.06	0.18	-9999	-0.5	70	70
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.034	0.081	-9999	-0.44	4	4
Syndecan-3/AgRP	-0.1	0.12	-9999	-0.24	219	219
Syndecan-3/AgRP/MC4R	-0.11	0.13	-9999	-0.45	17	17
Fyn/Cortactin	-0.001	0.016	-9999	-0.35	1	1
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.01	0.046	-9999	-0.24	20	20
IL8	-0.01	0.1	-9999	-0.51	20	20
Syndecan-3/Fyn/Cortactin	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.042	0.12	-9999	-0.37	58	58
Gamma Secretase	-0.001	0.018	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.012	0.1	0.5	22	-10000	0	22
PI3K Class IB/PDE3B	-0.012	0.1	-10000	0	-0.5	22	22
PDE3B	-0.012	0.1	-10000	0	-0.5	22	22

×

Nongenotropic Androgen signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.038	0.094	-10000	0	-0.27	73	73
regulation of S phase of mitotic cell cycle	-0.011	0.088	-10000	0	-0.23	70	70
GNAO1	0.003	0.06	-10000	0	-0.51	7	7
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	0	0.001	-10000	0	-10000	0	0
PELP1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0	0.091	-10000	0	-0.32	13	13
T-DHT/AR	-0.051	0.12	-10000	0	-0.36	72	72
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.006	27	27
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
mol:GDP	-0.054	0.14	-10000	0	-0.4	70	70
cell proliferation	0.002	0.13	-10000	0	-0.44	27	27
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.011	0.19	-10000	0	-0.8	27	27
mol:Ca2+	-0.01	0.021	-10000	0	-0.065	44	44
MAPK3	0.002	0.11	-10000	0	-0.45	13	13
MAPK1	0.006	0.065	-10000	0	-0.26	13	13
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
mol:IP3	0	0.001	-10000	0	-0.004	27	27
cAMP biosynthetic process	0.009	0.019	-10000	0	-10000	0	0
GNG2	0.008	0.032	-10000	0	-0.5	2	2
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	27	27
HRAS/GTP	-0.034	0.083	-10000	0	-0.28	13	13
actin cytoskeleton reorganization	0	0.01	-10000	0	-0.23	1	1
SRC	0.01	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	27	27
PI3K	-0.001	0.013	-10000	0	-0.3	1	1
apoptosis	-0.003	0.12	0.45	27	-10000	0	27
T-DHT/AR/PELP1	-0.042	0.1	-10000	0	-0.3	72	72
HRAS/GDP	-0.051	0.13	-10000	0	-0.37	70	70
CREB1	0.001	0.13	-10000	0	-0.48	27	27
RAC1-CDC42/GTP	0	0.01	-10000	0	-0.23	1	1
AR	-0.062	0.18	-10000	0	-0.5	72	72
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.006	0.091	-10000	0	-0.3	13	13
RAC1-CDC42/GDP	-0.048	0.12	-10000	0	-0.35	70	70
T-DHT/AR/PELP1/Src	-0.037	0.093	-10000	0	-0.27	72	72
MAP2K2	0	0.091	-10000	0	-0.32	13	13
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.088	-10000	0	-0.23	70	70
GNAZ	-0.031	0.14	-10000	0	-0.5	41	41
SHBG	0.009	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.004	0.077	-10000	0	-0.39	4	4
mol:T-DHT	0	0	-10000	0	-0.003	14	14
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.006	0.032	-10000	0	-0.36	4	4
Gi family/GTP	-0.035	0.081	-10000	0	-0.35	16	16
CDC42	0.01	0	-10000	0	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.03	0.12	-9999	-0.47	14	14
FZD6	0.009	0.022	-9999	-0.5	1	1
WNT6	-0.023	0.12	-9999	-0.51	32	32
WNT4	-0.019	0.12	-9999	-0.5	29	29
FZD3	0.009	0.023	-9999	-0.51	1	1
WNT5A	0.004	0.055	-9999	-0.5	6	6
WNT11	-0.057	0.17	-9999	-0.5	67	67

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.13	0.22	-9999	-0.5	137	137
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.009	0.023	-9999	-0.51	1	1
HIF1A/p53	0.005	0.034	-9999	-10000	0	0
HIF1A	-0.001	0.036	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0.011	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.14	0.24	-9999	-0.51	152	152
ARNT/IPAS	-0.094	0.16	-9999	-0.35	137	137
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.005	0.034	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.013	-9999	-0.3	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.005	0.034	-9999	-10000	0	0
PHD1-3/OS9	-0.066	0.11	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	-0.011	0.019	-9999	-10000	0	0
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.005	0.034	-9999	-10000	0	0
EGLN3	-0.12	0.22	-9999	-0.51	130	130
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.024	0.009	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.068	0.12	-9999	-0.25	152	152

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.003	0.007	-9999	-10000	0	0
REL	0.01	0.001	-9999	-10000	0	0
HDAC7	0.023	0.089	-9999	-0.47	3	3
JUN	0.007	0.039	-9999	-0.5	3	3
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
KAT5	0.01	0	-9999	-10000	0	0
MAPK14	0.006	0.069	-9999	-0.36	17	17
FOXO1	0.009	0.022	-9999	-0.5	1	1
T-DHT/AR	0.02	0.094	-9999	-0.42	6	6
MAP2K6	-0.007	0.093	-9999	-0.51	17	17
BRM/BAF57	-0.003	0.031	-9999	-0.35	4	4
MAP2K4	0.01	0.004	-9999	-10000	0	0
SMARCA2	0.006	0.045	-9999	-0.5	4	4
PDE9A	-0.043	0.17	-9999	-1.2	8	8
NCOA2	0.005	0.05	-9999	-0.5	5	5
CEBPA	-0.016	0.11	-9999	-0.5	26	26
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.021	0.13	-9999	-0.45	20	20
NR0B1	-0.1	0.21	-9999	-0.51	107	107
EGR1	-0.018	0.12	-9999	-0.5	28	28
RXRs/9cRA	-0.14	0.13	-9999	-0.26	267	267
AR/RACK1/Src	-0.001	0.065	-9999	-0.36	3	3
AR/GR	-0.008	0.096	-9999	-0.3	26	26
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
RCHY1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.018	0.009	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.002	0.068	-9999	-0.38	3	3
SRC	0.023	0.054	-9999	-0.31	2	2
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.06	0.097	-9999	-0.45	6	6
APPBP2	0.01	0.003	-9999	-10000	0	0
TRIM24	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.013	0.069	-9999	-0.37	4	4
TMPRSS2	-0.099	0.3	-9999	-1.1	42	42
RXRG	-0.26	0.25	-9999	-0.5	267	267
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.01	0	-9999	-10000	0	0
RXRB	0.01	0	-9999	-10000	0	0
CARM1	0.009	0.002	-9999	-10000	0	0
NR2C2	0.01	0	-9999	-10000	0	0
KLK2	0.013	0.096	-9999	-0.4	7	7
AR	-0.013	0.11	-9999	-0.27	70	70
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.008	0.032	-9999	-0.51	2	2
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.031	0.14	-9999	-0.5	41	41
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	-0.17	0.24	-9999	-0.51	179	179
T-DHT/AR/RACK1/Src	0.019	0.068	-9999	-0.38	3	3
positive regulation of transcription	-0.031	0.14	-9999	-0.5	41	41
DNAJA1	0.01	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.008	-9999	-10000	0	0
NCOA1	0.012	0.003	-9999	-10000	0	0
SPDEF	-0.16	0.24	-9999	-0.51	169	169
T-DHT/AR/TIF2	0.026	0.051	-9999	-0.25	1	1
T-DHT/AR/Hsp90	0.013	0.069	-9999	-0.37	4	4
GSK3B	0.01	0.003	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.019	0.058	-9999	-0.3	7	7
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.01	0.002	-9999	-10000	0	0
POU2F1	0.016	0.023	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.06	0.12	-9999	-0.36	37	37
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.001	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.046	-9999	-0.32	9	9
EPHB2	-0.047	0.16	-9999	-0.51	56	56
Syndecan-2/TACI	-0.013	0.095	-9999	-0.3	52	52
LAMA1	-0.017	0.12	-9999	-0.51	27	27
Syndecan-2/alpha2 ITGB1	-0.058	0.11	-9999	-0.49	5	5
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.003	0.029	-9999	-0.3	5	5
ITGA5	0.008	0.032	-9999	-0.5	2	2
BAX	0.029	0.027	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.003	0.026	-9999	-0.26	5	5
LAMA3	-0.093	0.2	-9999	-0.5	104	104
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.097	0.21	-9999	-0.5	108	108
Syndecan-2/MMP2	0.015	0.033	-9999	-0.29	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.011	0.062	-9999	-0.36	16	16
dendrite morphogenesis	-0.019	0.1	-9999	-0.3	61	61
Syndecan-2/GM-CSF	-0.014	0.096	-9999	-0.3	52	52
determination of left/right symmetry	0.012	0.036	-9999	-0.35	5	5
Syndecan-2/PKC delta	0.016	0.03	-9999	-0.29	5	5
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	-0.004	0.088	-9999	-0.26	52	52
MAPK1	-0.004	0.088	-9999	-0.26	52	52
Syndecan-2/RACK1	-0.002	0.024	-9999	-0.24	5	5
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.036	-9999	-0.35	5	5
ITGA2	-0.006	0.09	-9999	-0.51	16	16
MAPK8	0.024	0.031	-9999	-0.29	5	5
Syndecan-2/alpha2/beta1 Integrin	-0.023	0.079	-9999	-0.5	5	5
Syndecan-2/Kininogen	-0.015	0.083	-9999	-0.3	40	40
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.026	0.025	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	-0.003	0.026	-9999	-0.26	5	5
extracellular matrix organization	0.016	0.03	-9999	-0.29	5	5
actin cytoskeleton reorganization	0.013	0.046	-9999	-0.32	9	9
Syndecan-2/Caveolin-2/Ras	-0.057	0.11	-9999	-0.26	113	113
Syndecan-2/Laminin alpha3	-0.047	0.13	-9999	-0.29	109	109
Syndecan-2/RasGAP	-0.002	0.022	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.001	0.022	-9999	-0.36	2	2
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.019	0.1	-9999	-0.3	61	61
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.031	0.024	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	-0.038	0.15	-9999	-0.51	47	47
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.011	0.062	-9999	-0.36	16	16
Syndecan-2/Synbindin	0.016	0.03	-9999	-0.29	5	5
TGFB1	0.01	0	-9999	-10000	0	0
CASP3	0.023	0.028	-9999	-0.26	5	5
FN1	0.005	0.05	-9999	-0.5	5	5
Syndecan-2/IL8	0.004	0.068	-9999	-0.3	25	25
SDC2	0.012	0.036	-9999	-0.35	5	5
KNG1	-0.03	0.13	-9999	-0.51	35	35
Syndecan-2/Neurofibromin	0.016	0.03	-9999	-0.29	5	5
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.038	0.15	-9999	-0.5	48	48
Syndecan-2/TGFB1	0.016	0.03	-9999	-0.29	5	5
Syndecan-2/Syntenin/PI-4-5-P2	-0.003	0.026	-9999	-0.26	5	5
Syndecan-2/Ezrin	-0.002	0.025	-9999	-0.26	5	5
PRKACA	0.023	0.028	-9999	-0.26	5	5
angiogenesis	0.004	0.068	-9999	-0.3	25	25
MMP2	0.009	0.023	-9999	-0.51	1	1
IL8	-0.01	0.1	-9999	-0.51	20	20
calcineurin-NFAT signaling pathway	-0.013	0.095	-9999	-0.3	52	52

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.022	-9999	-0.5	1	1
alphaV beta3 Integrin	-0.019	0.081	-9999	-0.36	28	28
PTK2	-0.039	0.11	-9999	-0.38	41	41
positive regulation of JNK cascade	-0.023	0.077	-9999	-0.28	41	41
CDC42/GDP	0.009	0.12	-9999	-0.38	41	41
Rac1/GDP	0.01	0.11	-9999	-0.37	41	41
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.028	0.094	-9999	-0.34	41	41
nectin-3/I-afadin	-0.029	0.097	-9999	-0.35	42	42
RAPGEF1	0.003	0.12	-9999	-0.42	41	41
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.005	0.14	-9999	-0.47	41	41
PDGFB-D/PDGFRB	0.009	0.022	-9999	-0.5	1	1
TLN1	0.002	0.084	-9999	-0.39	15	15
Rap1/GTP	-0.024	0.081	-9999	-0.3	41	41
IQGAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.029	0.097	-9999	-0.35	42	42
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	0.002	0.14	-9999	-0.46	41	41
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.02	0.069	-9999	-0.49	2	2
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.008	0.052	-9999	-0.36	11	11
positive regulation of lamellipodium assembly	-0.025	0.081	-9999	-0.3	42	42
PVRL1	-0.001	0.075	-9999	-0.51	11	11
PVRL3	-0.032	0.14	-9999	-0.5	42	42
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2
CLDN1	-0.009	0.097	-9999	-0.51	19	19
JAM-A/CLDN1	-0.031	0.09	-9999	-0.28	58	58
SRC	-0.045	0.14	-9999	-0.53	41	41
ITGB3	-0.018	0.12	-9999	-0.51	28	28
nectin-1(dimer)/I-afadin/I-afadin	-0.008	0.052	-9999	-0.36	11	11
FARP2	-0.002	0.13	-9999	-0.45	41	41
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.024	0.08	-9999	-0.29	42	42
nectin-1/I-afadin	-0.008	0.052	-9999	-0.36	11	11
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.03	0.091	-9999	-0.3	52	52
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.009	0.022	-9999	-0.5	1	1
positive regulation of filopodium formation	-0.023	0.077	-9999	-0.28	41	41
alphaV/beta3 Integrin/Talin	-0.001	0.096	-9999	-0.48	8	8
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.004	0.088	-9999	-0.43	14	14
VAV2	-0.003	0.14	-9999	-0.46	42	42
RAP1/GDP	-0.028	0.095	-9999	-0.35	41	41
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.024	0.08	-9999	-0.29	42	42
nectin-3(dimer)/I-afadin/I-afadin	-0.029	0.097	-9999	-0.35	42	42
Rac1/GTP	-0.03	0.098	-9999	-0.36	42	42
PTPRM	-0.026	0.092	-9999	-0.47	14	14
E-cadherin/beta catenin/alpha catenin	-0.006	0.035	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.009	0.035	-10000	0	-10000	0	0
oxygen homeostasis	0	0.013	-10000	0	-10000	0	0
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.009	0.023	-10000	0	-0.51	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.065	0.11	-10000	0	-0.39	30	30
EPO	-0.026	0.22	-10000	0	-0.66	15	15
FIH (dimer)	0.011	0.012	-10000	0	-10000	0	0
APEX1	0.012	0.012	-10000	0	-10000	0	0
SERPINE1	-0.047	0.26	-10000	0	-0.69	27	27
FLT1	-0.009	0.052	-10000	0	-0.89	1	1
ADORA2A	-0.042	0.24	-10000	0	-0.65	26	26
germ cell development	-0.06	0.26	-10000	0	-0.65	32	32
SLC11A2	-0.045	0.25	-10000	0	-0.67	26	26
BHLHE40	-0.045	0.25	-10000	0	-0.67	26	26
HIF1AN	0.011	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.086	0.14	-10000	0	-0.44	43	43
ETS1	0.02	0.024	-10000	0	-0.52	1	1
CITED2	-0.011	0.071	-10000	0	-1.1	2	2
KDR	-0.033	0.19	-10000	0	-1.2	13	13
PGK1	-0.045	0.25	-10000	0	-0.67	26	26
SIRT1	0.01	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.047	0.29	-10000	0	-0.74	33	33
EPAS1	-0.043	0.16	-10000	0	-0.4	49	49
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	-0.071	0.3	-10000	0	-0.73	50	50
EFNA1	-0.045	0.25	-10000	0	-0.68	26	26
FXN	-0.042	0.24	-10000	0	-0.65	26	26
POU5F1	-0.063	0.27	-10000	0	-0.68	32	32
neuron apoptosis	0.046	0.28	0.71	33	-10000	0	33
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	-0.12	0.23	-10000	0	-0.52	130	130
EGLN2	0.01	0.012	-10000	0	-10000	0	0
EGLN1	0.011	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.013	-10000	0	-0.3	1	1
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.012	0.012	-10000	0	-10000	0	0
SLC2A1	-0.12	0.31	-10000	0	-0.64	84	84
TWIST1	-0.081	0.29	-10000	0	-0.67	56	56
ELK1	0.016	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.084	0.14	-10000	0	-0.44	41	41
VEGFA	-0.045	0.25	-10000	0	-0.67	26	26
CREBBP	0.01	0	-10000	0	-10000	0	0

×

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	0.01	0.001	-9999	-10000	0	0
SVIL	0.01	0.001	-9999	-10000	0	0
ZNF318	0.009	0.007	-9999	-10000	0	0
JMJD2C	-0.001	0.018	-9999	-0.078	26	26
T-DHT/AR/Ubc9	-0.046	0.12	-9999	-0.32	72	72
CARM1	0.01	0	-9999	-10000	0	0
PRDX1	0.009	0.023	-9999	-0.51	1	1
PELP1	0.01	0.001	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.01	0.002	-9999	-10000	0	0
PTK2B	0.008	0.032	-9999	-0.5	2	2
MED1	0.01	0.002	-9999	-10000	0	0
MAK	-0.008	0.091	-9999	-0.5	17	17
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.005	0.05	-9999	-0.5	5	5
GSN	0.01	0.001	-9999	-10000	0	0
NCOA2	0.005	0.05	-9999	-0.5	5	5
NCOA6	0.01	0.001	-9999	-10000	0	0
DNA-PK	0.001	0.008	-9999	-10000	0	0
NCOA4	0.01	0	-9999	-10000	0	0
PIAS3	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.036	0.13	-9999	-0.72	17	17
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.01	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.057	0.13	-9999	-0.33	89	89
FHL2	-0.05	0.13	-9999	-0.44	18	18
RANBP9	0.01	0.001	-9999	-10000	0	0
JMJD1A	0	0.04	-9999	-0.13	47	47
CDK6	0.008	0.032	-9999	-0.5	2	2
TGFB1I1	0.007	0.039	-9999	-0.5	3	3
T-DHT/AR/CyclinD1	-0.049	0.12	-9999	-0.33	77	77
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.04	0.14	-9999	-0.34	80	80
CTDSP1	0.01	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.004	-9999	-10000	0	0
BRCA1	0.007	0.039	-9999	-0.51	3	3
TCF4	0.008	0.032	-9999	-0.5	2	2
CDKN2A	-0.14	0.24	-9999	-0.51	152	152
SRF	0.006	0.026	-9999	-10000	0	0
NKX3-1	-0.046	0.12	-9999	-0.46	25	25
KLK3	0.016	0.045	-9999	-10000	0	0
TMF1	0.01	0.001	-9999	-10000	0	0
HNRNPA1	0.01	0.002	-9999	-10000	0	0
AOF2	0	0.003	-9999	-10000	0	0
APPL1	0.018	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.048	0.12	-9999	-0.32	73	73
AR	-0.068	0.18	-9999	-0.52	72	72
UBA3	0.01	0.001	-9999	-10000	0	0
PATZ1	0.01	0.002	-9999	-10000	0	0
PAWR	0.01	0.001	-9999	-10000	0	0
PRKDC	0.01	0.001	-9999	-10000	0	0
PA2G4	0.01	0.003	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.034	0.11	-9999	-0.29	72	72
RPS6KA3	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.045	0.12	-9999	-0.32	72	72
LATS2	0.01	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.036	0.11	-9999	-0.3	72	72
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0.003	0.059	-9999	-0.5	7	7
KLK2	-0.042	0.089	-9999	-0.36	26	26
CASP8	0.009	0.022	-9999	-0.5	1	1
T-DHT/AR/TIF2/CARM1	-0.038	0.11	-9999	-0.29	76	76
TMPRSS2	-0.096	0.27	-9999	-0.96	43	43
CCND1	0.003	0.059	-9999	-0.5	7	7
PIAS1	0.01	0.003	-9999	-10000	0	0
mol:T-DHT	-0.007	0.026	-9999	-0.076	36	36
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.01	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.048	0.12	-9999	-0.32	74	74
CMTM2	-0.084	0.2	-9999	-0.5	95	95
SNURF	-0.009	0.096	-9999	-0.5	19	19
ZMIZ1	0.005	0.022	-9999	-10000	0	0
CCND3	0.01	0	-9999	-10000	0	0
TGIF1	0.01	0.002	-9999	-10000	0	0
FKBP4	0.009	0.023	-9999	-0.51	1	1

×

PLK2 and PLK4 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
PLK2	0.009	0.022	-9999	-0.5	1	1
PLK4	-0.017	0.12	-9999	-0.51	27	27
regulation of centriole replication	-0.003	0.086	-9999	-0.36	28	28

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.024	-9999	-10000	0	0
VDR	0.008	0.032	-9999	-0.5	2	2
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.091	0.14	-9999	-0.46	10	10
RXRs/LXRs/DNA/Oxysterols	-0.073	0.14	-9999	-0.47	20	20
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.003	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.003	0.078	-9999	-0.46	1	1
RXRs/NUR77	-0.17	0.18	-9999	-0.48	65	65
RXRs/PPAR	-0.13	0.16	-9999	-0.44	53	53
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.023	-9999	-0.36	2	2
RARs/VDR/DNA/Vit D3	-0.002	0.021	-9999	-0.24	4	4
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.008	0.032	-9999	-0.5	2	2
RARs/RARs/DNA/9cRA	-0.001	0.016	-9999	-0.25	2	2
RARG	0.01	0	-9999	-10000	0	0
RPS6KB1	0.042	0.04	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.003	0.078	-9999	-0.46	1	1
THRA	0.01	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.023	-9999	-0.36	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.14	-9999	-0.37	10	10
NR1H4	-0.03	0.13	-9999	-0.51	36	36
RXRs/LXRs/DNA	-0.095	0.14	-9999	-0.39	10	10
NR1H2	0.013	0.007	-9999	-10000	0	0
NR1H3	0.013	0.008	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.14	-9999	-0.32	12	12
NR4A1	-0.093	0.2	-9999	-0.5	104	104
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.097	0.12	-9999	-0.31	30	30
RXRG	-0.25	0.25	-9999	-0.5	267	267
RXR alpha/CCPG	0.017	0.004	-9999	-10000	0	0
RXRA	0.013	0.007	-9999	-10000	0	0
RXRB	0.013	0.008	-9999	-10000	0	0
THRB	-0.042	0.15	-9999	-0.5	52	52
PPARG	-0.061	0.18	-9999	-0.5	71	71
PPARD	0.01	0	-9999	-10000	0	0
TNF	-0.082	0.21	-9999	-1	19	19
mol:Oxysterols	0.003	0.009	-9999	-10000	0	0
cholesterol transport	-0.072	0.13	-9999	-0.47	20	20
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.008	0.032	-9999	-0.5	2	2
RXRs/NUR77/BCL2	-0.15	0.16	-9999	-0.4	76	76
SREBF1	-0.06	0.12	-9999	-0.53	10	10
RXRs/RXRs/DNA/9cRA	-0.12	0.14	-9999	-0.37	10	10
ABCA1	-0.062	0.14	-9999	-0.62	11	11
RARs/THRs	-0.025	0.074	-9999	-0.49	1	1
RXRs/FXR	-0.14	0.16	-9999	-0.46	30	30
BCL2	0.007	0.039	-9999	-0.5	3	3

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.047	-9999	-0.48	4	4
Syndecan-4/Syndesmos	-0.024	0.084	-9999	-0.52	2	2
positive regulation of JNK cascade	-0.053	0.081	-9999	-0.44	4	4
Syndecan-4/ADAM12	-0.11	0.16	-9999	-0.37	96	96
CCL5	0.005	0.05	-9999	-0.5	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.008	0.032	-9999	-0.5	2	2
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.007	0.076	-9999	-0.52	11	11
ADAM12	-0.16	0.24	-9999	-0.51	174	174
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.037	0.05	-9999	-0.16	1	1
Syndecan-4/Laminin alpha1	-0.037	0.1	-9999	-0.4	14	14
Syndecan-4/CXCL12/CXCR4	-0.036	0.098	-9999	-0.46	4	4
Syndecan-4/Laminin alpha3	-0.073	0.13	-9999	-0.36	43	43
MDK	-0.15	0.24	-9999	-0.51	157	157
Syndecan-4/FZD7	-0.024	0.085	-9999	-0.46	3	3
Syndecan-4/Midkine	-0.099	0.14	-9999	-0.37	62	62
FZD7	0.009	0.022	-9999	-0.5	1	1
Syndecan-4/FGFR1/FGF	-0.072	0.1	-9999	-0.49	9	9
THBS1	0.007	0.039	-9999	-0.5	3	3
integrin-mediated signaling pathway	-0.04	0.1	-9999	-0.4	11	11
positive regulation of MAPKKK cascade	-0.053	0.081	-9999	-0.44	4	4
Syndecan-4/TACI	-0.046	0.12	-9999	-0.38	28	28
CXCR4	0.01	0	-9999	-10000	0	0
cell adhesion	0.006	0.038	-9999	-0.29	6	6
Syndecan-4/Dynamin	-0.024	0.084	-9999	-0.52	2	2
Syndecan-4/TSP1	-0.025	0.089	-9999	-0.63	2	2
Syndecan-4/GIPC	-0.024	0.084	-9999	-0.52	2	2
Syndecan-4/RANTES	-0.026	0.086	-9999	-0.52	2	2
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.017	0.12	-9999	-0.51	27	27
LAMA3	-0.093	0.2	-9999	-0.5	104	104
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.016	0.039	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.024	0.084	-9999	-0.52	2	2
TFPI	-0.012	0.1	-9999	-0.5	22	22
F2	-0.071	0.18	-9999	-0.51	74	74
alpha5/beta1 Integrin	-0.001	0.022	-9999	-0.36	2	2
positive regulation of cell adhesion	-0.077	0.14	-9999	-0.49	10	10
ACTN1	0.01	0	-9999	-10000	0	0
TNC	-0.026	0.13	-9999	-0.51	36	36
Syndecan-4/CXCL12	-0.039	0.1	-9999	-0.38	14	14
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.022	0.12	-9999	-0.5	32	32
TNFRSF13B	-0.038	0.15	-9999	-0.51	47	47
FGF2	-0.063	0.18	-9999	-0.5	74	74
FGFR1	0.007	0.039	-9999	-0.5	3	3
Syndecan-4/PI-4-5-P2	-0.03	0.084	-9999	-0.52	2	2
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.05	-9999	-0.49	5	5
cell migration	-0.016	0.021	-9999	-10000	0	0
PRKCD	0.012	0.006	-9999	-10000	0	0
vasculogenesis	-0.024	0.086	-9999	-0.6	2	2
SDC4	-0.031	0.088	-9999	-0.55	2	2
Syndecan-4/Tenascin C	-0.041	0.1	-9999	-0.41	11	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.029	0.04	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.024	0.084	-9999	-0.52	2	2
MMP9	-0.1	0.21	-9999	-0.51	112	112
Rac1/GTP	0.006	0.039	-9999	-0.29	6	6
cytoskeleton organization	-0.023	0.082	-9999	-0.5	2	2
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.034	0.098	-9999	-0.54	3	3

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.041	0.11	0.35	59	-10000	0	59
KIRREL	-0.01	0.092	-10000	0	-0.5	17	17
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.041	0.11	-10000	0	-0.36	59	59
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.028	0.079	-10000	0	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.005	0.058	-10000	0	-0.23	17	17
FYN	-0.012	0.076	-10000	0	-0.24	17	17
mol:Ca2+	-0.028	0.078	-10000	0	-0.26	4	4
mol:DAG	-0.028	0.079	-10000	0	-0.26	4	4
NPHS2	-0.002	0.015	-10000	0	-10000	0	0
mol:IP3	-0.028	0.079	-10000	0	-0.26	4	4
regulation of endocytosis	-0.023	0.065	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.029	0.081	-10000	0	-0.25	59	59
establishment of cell polarity	-0.041	0.11	-10000	0	-0.35	59	59
Nephrin/NEPH1/podocin/NCK1-2	-0.025	0.07	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	-0.011	0.071	-10000	0	-10000	0	0
NPHS1	-0.035	0.14	-10000	0	-0.5	42	42
Nephrin/NEPH1/podocin	-0.026	0.071	-10000	0	-0.25	17	17
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.028	0.079	-10000	0	-0.26	4	4
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.028	0.079	-10000	0	-0.26	16	16
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.031	0.11	-10000	0	-0.3	39	39
cytoskeleton organization	0.007	0.067	-10000	0	-10000	0	0
Nephrin/NEPH1	-0.028	0.078	-10000	0	-0.25	59	59
Nephrin/NEPH1/ZO-1	-0.031	0.087	-10000	0	-0.27	59	59

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.019	0.081	-9999	-0.36	28	28
AKT1	0.028	0.12	-9999	-0.51	15	15
PTK2B	-0.01	0.13	-9999	-0.58	15	15
VEGFR2 homodimer/Frs2	-0.022	0.14	-9999	-0.68	14	14
CAV1	-0.31	0.25	-9999	-0.5	326	326
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.041	0.12	-9999	-0.65	13	13
endothelial cell proliferation	0.034	0.12	-9999	-0.49	14	14
mol:Ca2+	0.003	0.12	-9999	-0.56	14	14
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.037	0.11	-9999	-0.6	13	13
RP11-342D11.1	-0.003	0.12	-9999	-0.57	14	14
CDH5	-0.055	0.17	-9999	-0.5	65	65
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0.008	0.032	-9999	-0.51	2	2
SHC2	0.001	0.067	-9999	-0.5	9	9
HRAS/GDP	-0.031	0.092	-9999	-0.48	14	14
SH2D2A	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.032	0.095	-9999	-0.48	16	16
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.04	0.12	-9999	-0.63	13	13
VEGFR1 homodimer	0.01	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.034	0.1	-9999	-0.53	14	14
GRB10	0.003	0.12	-9999	-0.56	14	14
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.064	0.16	-9999	-0.56	35	35
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.006	0.085	-9999	-0.35	14	14
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.008	0.032	-9999	-0.51	2	2
oxygen and reactive oxygen species metabolic process	-0.037	0.11	-9999	-0.59	13	13
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.003	0.08	-9999	-0.5	13	13
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.041	0.12	-9999	-0.63	13	13
mol:GDP	-0.033	0.099	-9999	-0.52	14	14
mol:NADP	0.024	0.1	-9999	-0.41	18	18
eNOS/Hsp90	0.028	0.098	-9999	-0.38	18	18
PIK3R1	0.009	0.022	-9999	-0.5	1	1
mol:IP3	0.003	0.12	-9999	-0.57	14	14
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.009	0.022	-9999	-0.5	1	1
VEGFA	0.011	0	-9999	-10000	0	0
VEGFC	0.006	0.045	-9999	-0.5	4	4
FAK1/Vinculin	0.005	0.14	-9999	-0.6	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.05	0.12	-9999	-0.61	14	14
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.046	0.17	-9999	-0.49	65	65
mol:L-citrulline	0.024	0.1	-9999	-0.41	18	18
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.038	0.12	-9999	-0.62	13	13
VEGFR2 homodimer/VEGFA homodimer	-0.04	0.12	-9999	-0.62	14	14
VEGFR2/3 heterodimer	-0.028	0.16	-9999	-0.38	70	70
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.004	0.13	-9999	-0.57	15	15
VEGFR2 homodimer	-0.029	0.16	-9999	-0.42	65	65
FLT1	0.01	0	-9999	-10000	0	0
NEDD4	0.01	0.022	-9999	-0.5	1	1
MAPK3	0.008	0.12	-9999	-0.54	14	14
MAPK1	0.008	0.12	-9999	-0.54	14	14
VEGFA145/NRP2	-0.002	0.027	-9999	-0.35	3	3
VEGFR1/2 heterodimer	-0.02	0.14	-9999	-0.36	65	65
KDR	-0.029	0.16	-9999	-0.42	65	65
VEGFA165/NRP1/VEGFR2 homodimer	-0.037	0.11	-9999	-0.57	15	15
SRC	0.01	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.008	0.12	-9999	-0.55	14	14
PI3K	-0.036	0.11	-9999	-0.58	15	15
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.04	0.12	-9999	-0.63	13	13
FES	0.002	0.12	-9999	-0.58	14	14
GAB1	-0.038	0.11	-9999	-0.59	14	14
VEGFR2 homodimer/VEGFA homodimer/Src	-0.04	0.12	-9999	-0.63	13	13
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.14	-9999	-0.4	52	52
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.04	0.12	-9999	-0.63	13	13
PI3K/GAB1	0.027	0.12	-9999	-0.54	14	14
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.036	0.11	-9999	-0.59	13	13
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.049	0.14	-9999	-0.63	19	19
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	0.003	0.12	-9999	-0.58	14	14
actin cytoskeleton reorganization	-0.04	0.12	-9999	-0.63	13	13
PTK2	-0.001	0.15	-9999	-0.66	15	15
EDG1	-0.003	0.12	-9999	-0.57	14	14
mol:DAG	0.003	0.12	-9999	-0.57	14	14
CaM/Ca2+	-0.033	0.1	-9999	-0.52	14	14
MAP2K3	0.01	0.12	-9999	-0.55	14	14
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.037	0.11	-9999	-0.58	14	14
PLCG1	0.003	0.12	-9999	-0.58	14	14
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.038	0.11	-9999	-0.59	14	14
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.04	0.12	-9999	-0.63	13	13
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.04	0.12	-9999	-0.63	13	13
cell migration	0.012	0.14	-9999	-0.59	14	14
mol:PI-3-4-5-P3	-0.034	0.1	-9999	-0.53	15	15
FYN	0.009	0.022	-9999	-0.5	1	1
VEGFB/NRP1	-0.034	0.1	-9999	-0.54	14	14
mol:NO	0.024	0.1	-9999	-0.41	18	18
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.03	0.092	-9999	-0.48	14	14
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.002	0.13	-9999	-0.58	14	14
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.018	0.12	-9999	-0.51	28	28
NOS3	0.023	0.11	-9999	-0.46	18	18
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.045	0.13	-9999	-0.64	16	16
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.009	0.12	-9999	-0.53	14	14
PRKCB	0.003	0.13	-9999	-0.56	16	16
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.004	0.12	-9999	-0.57	14	14
VEGFR1/2 heterodimer/VEGFA homodimer	-0.04	0.12	-9999	-0.63	13	13
VEGFA165/NRP2	-0.002	0.027	-9999	-0.35	3	3
MAPKKK cascade	-0.03	0.09	-9999	-0.48	14	14
NRP2	0.007	0.039	-9999	-0.5	3	3
VEGFC homodimer	0.006	0.045	-9999	-0.5	4	4
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	0.005	0.14	-9999	-0.6	15	15
MAP3K13	0.003	0.12	-9999	-0.58	14	14
PDPK1	0.026	0.11	-9999	-0.47	15	15

×

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

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.018	0.099	-10000	0	-0.39	25	25
CRKL	0.014	0.099	-10000	0	-0.41	24	24
HRAS	0.026	0.11	-10000	0	-0.39	26	26
mol:PIP3	0.003	0.093	0.22	1	-0.41	23	24
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	0.008	0.1	-10000	0	-0.44	24	24
FOXO3	0.019	0.09	-10000	0	-0.38	23	23
AKT1	0.013	0.096	-10000	0	-0.41	23	23
BAD	0.019	0.09	-10000	0	-0.38	23	23
megakaryocyte differentiation	-0.015	0.13	-10000	0	-0.47	29	29
GSK3B	0.019	0.09	-10000	0	-0.38	23	23
RAF1	0.032	0.088	-10000	0	-0.39	11	11
SHC1	0.008	0.032	-10000	0	-0.51	2	2
STAT3	0.009	0.1	-10000	0	-0.44	23	23
STAT1	0.004	0.22	-10000	0	-0.95	24	24
HRAS/SPRED1	-0.02	0.074	-10000	0	-0.39	11	11
cell proliferation	0.01	0.1	-10000	0	-0.44	23	23
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.009	0.1	-10000	0	-0.44	23	23
HRAS/SPRED2	-0.02	0.074	-10000	0	-0.39	11	11
LYN/TEC/p62DOK	-0.02	0.087	-10000	0	-0.41	23	23
MAPK3	0.036	0.066	-10000	0	-0.28	9	9
STAP1	0.002	0.11	-10000	0	-0.45	26	26
GRAP2	-0.006	0.088	-10000	0	-0.5	16	16
JAK2	-0.042	0.18	-10000	0	-0.82	24	24
STAT1 (dimer)	0.005	0.21	-10000	0	-0.93	24	24
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.023	0.09	-10000	0	-0.41	24	24
actin filament polymerization	0.009	0.1	-10000	0	-0.44	23	23
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	0.009	0.15	-10000	0	-0.59	26	26
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
CBL/CRKL/GRB2	-0.019	0.08	-10000	0	-0.37	23	23
PI3K	-0.007	0.095	-10000	0	-0.42	23	23
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.001	0.26	-10000	0	-1.2	23	23
MAPK8	0.009	0.1	-10000	0	-0.44	23	23
STAT3 (dimer)	0.01	0.1	-10000	0	-0.44	23	23
positive regulation of transcription	0.034	0.056	-10000	0	-0.23	9	9
mol:GDP	-0.026	0.096	-10000	0	-0.41	26	26
PIK3C2B	0.009	0.1	-10000	0	-0.45	23	23
CBL/CRKL	0.02	0.094	-10000	0	-0.39	23	23
FER	0.009	0.1	-10000	0	-0.44	23	23
SH2B3	0.009	0.1	-10000	0	-0.44	24	24
PDPK1	0.009	0.087	-10000	0	-0.37	23	23
SNAI2	0.007	0.11	-10000	0	-0.46	24	24
positive regulation of cell proliferation	0.01	0.17	-10000	0	-0.72	24	24
KITLG	0.009	0.048	-10000	0	-0.53	4	4
cell motility	0.01	0.17	-10000	0	-0.72	24	24
PTPN6	0.002	0.007	-10000	0	-10000	0	0
EPOR	0.029	0.066	-10000	0	-10000	0	0
STAT5A (dimer)	0.012	0.14	-10000	0	-0.6	24	24
SOCS1	0.008	0.032	-10000	0	-0.51	2	2
cell migration	0.001	0.12	0.46	24	-10000	0	24
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.004	0.046	-10000	0	-0.51	4	4
VAV1	0.005	0.05	-10000	0	-0.5	5	5
GRB10	0.009	0.1	-10000	0	-0.44	23	23
PTPN11	0.009	0.004	-10000	0	-10000	0	0
SCF/KIT	0.003	0.11	-10000	0	-0.46	24	24
GO:0007205	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	0.035	0.071	-10000	0	-0.31	9	9
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.015	0.26	-10000	0	-1.2	23	23
MAP2K2	0.035	0.071	-10000	0	-0.31	9	9
SHC/Grb2/SOS1	-0.021	0.092	-10000	0	-0.43	23	23
STAT5A	0.012	0.14	-10000	0	-0.62	24	24
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	0.007	0.11	-10000	0	-0.45	24	24
SHC/GRAP2	-0.012	0.068	-10000	0	-0.37	17	17
PTPRO	-0.015	0.14	-10000	0	-0.48	29	29
SH2B2	0.009	0.1	-10000	0	-0.44	23	23
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	-0.002	0.12	-10000	0	-0.46	24	24
CREBBP	0.029	0.007	-10000	0	-10000	0	0
BCL2	0.027	0.086	-10000	0	-1.2	1	1

×

IL12-mediated 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
IL12/IL12R/TYK2/JAK2/SOCS1	0.025	0.092	-10000	0	-0.35	11	11
TBX21	-0.004	0.34	-10000	0	-1.2	30	30
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.002	0.091	-10000	0	-0.52	15	15
GADD45B	0.016	0.27	-10000	0	-1	20	20
IL12RB2	-0.024	0.14	-10000	0	-0.5	42	42
GADD45G	0.014	0.27	-10000	0	-1	20	20
natural killer cell activation	0.008	0.016	-10000	0	-10000	0	0
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.004	0.071	-10000	0	-0.5	10	10
IL2RA	-0.026	0.13	-10000	0	-0.51	36	36
IFNG	-0.032	0.14	-10000	0	-0.51	41	41
STAT3 (dimer)	0.026	0.23	-10000	0	-0.78	22	22
HLA-DRB5	-0.043	0.16	-10000	0	-0.5	54	54
FASLG	0.014	0.29	-10000	0	-1.1	22	22
NF kappa B2 p52/RelB	-0.082	0.22	-10000	0	-0.91	24	24
CD4	0	0.07	-10000	0	-0.5	10	10
SOCS1	0.008	0.032	-10000	0	-0.51	2	2
EntrezGene:6955	0.001	0.008	-10000	0	-10000	0	0
CD3D	0.008	0.04	-10000	0	-0.51	3	3
CD3E	0.006	0.05	-10000	0	-0.5	5	5
CD3G	0.001	0.071	-10000	0	-0.5	10	10
IL12Rbeta2/JAK2	-0.003	0.11	-10000	0	-0.35	44	44
CCL3	0.017	0.27	-10000	0	-0.98	23	23
CCL4	0.016	0.28	-10000	0	-1	23	23
HLA-A	0.011	0.005	-10000	0	-10000	0	0
IL18/IL18R	0.016	0.12	-10000	0	-0.36	43	43
NOS2	-0.045	0.41	-10000	0	-1.1	58	58
IL12/IL12R/TYK2/JAK2/SPHK2	0.025	0.092	-10000	0	-0.35	11	11
IL1R1	0.018	0.27	-10000	0	-0.98	22	22
IL4	-0.004	0.016	-10000	0	-10000	0	0
JAK2	0.015	0.035	-10000	0	-0.5	2	2
EntrezGene:6957	0.001	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.014	0.16	-10000	0	-0.9	11	11
RAB7A	0.036	0.22	-10000	0	-0.82	15	15
lysosomal transport	0.038	0.22	-10000	0	-0.77	15	15
FOS	-0.031	0.32	-10000	0	-1.1	36	36
STAT4 (dimer)	0.035	0.25	-10000	0	-0.91	20	20
STAT5A (dimer)	-0.095	0.23	-10000	0	-0.82	33	33
GZMA	0.015	0.28	-10000	0	-1.1	21	21
GZMB	-0.001	0.32	-10000	0	-1.2	28	28
HLX	0.005	0.05	-10000	0	-0.5	5	5
LCK	0.015	0.29	-10000	0	-1	24	24
TCR/CD3/MHC II/CD4	-0.019	0.16	-10000	0	-0.56	29	29
IL2/IL2R	-0.022	0.078	-10000	0	-0.28	41	41
MAPK14	0.022	0.27	-10000	0	-0.94	21	21
CCR5	0.016	0.26	-10000	0	-1.1	17	17
IL1B	-0.014	0.13	-10000	0	-0.51	31	31
STAT6	0.029	0.086	-10000	0	-0.24	12	12
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.013	0.059	-10000	0	-0.52	6	6
CD8A	0.005	0.056	-10000	0	-0.5	6	6
CD8B	0.003	0.064	-10000	0	-0.5	8	8
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.025	0.091	0.35	11	-10000	0	11
IL2RB	0.008	0.032	-10000	0	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.23	-10000	0	-0.81	20	20
IL2RG	0.005	0.05	-10000	0	-0.5	5	5
IL12	0.021	0.064	-10000	0	-0.36	12	12
STAT5A	0.009	0.022	-10000	0	-0.5	1	1
CD247	0.005	0.055	-10000	0	-0.5	6	6
IL2	0.006	0.005	-10000	0	-10000	0	0
SPHK2	0.009	0.022	-10000	0	-0.5	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.011	0.058	-10000	0	-0.51	6	6
IL12/IL12R/TYK2/JAK2	0.011	0.31	-10000	0	-1	27	27
MAP2K3	0.019	0.27	-10000	0	-0.96	21	21
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.017	0.27	-10000	0	-0.93	23	23
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.009	0.096	-10000	0	-0.5	19	19
IL18RAP	-0.006	0.1	-10000	0	-0.5	20	20
IL12Rbeta1/TYK2	0.014	0.071	-10000	0	-0.38	15	15
EOMES	-0.009	0.14	-10000	0	-1.2	7	7
STAT1 (dimer)	0.02	0.23	-10000	0	-0.77	23	23
T cell proliferation	0.03	0.21	-10000	0	-0.67	20	20
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.009	0.11	-10000	0	-0.5	23	23
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.078	0.18	-10000	0	-0.72	22	22
ATF2	0.03	0.25	-10000	0	-0.85	21	21

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.013	0.1	-9999	-0.5	23	23
GNB1/GNG2	-0.045	0.097	-9999	-0.44	14	14
mol:DAG	-0.008	0.1	-9999	-0.4	14	14
PLCG1	-0.009	0.11	-9999	-0.41	14	14
YES1	-0.021	0.11	-9999	-0.44	14	14
FZD3	0.009	0.023	-9999	-0.51	1	1
FZD6	0.009	0.022	-9999	-0.5	1	1
G protein	-0.04	0.092	-9999	-0.41	14	14
MAP3K7	-0.017	0.12	-9999	-0.39	27	27
mol:Ca2+	-0.008	0.1	-9999	-0.38	14	14
mol:IP3	-0.008	0.1	-9999	-0.4	14	14
NLK	-0.002	0.006	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.025	0.13	-9999	-0.42	28	28
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.03	0.12	-9999	-0.47	14	14
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.021	0.11	-9999	-0.44	14	14
GO:0007205	-0.008	0.1	-9999	-0.41	12	12
WNT6	-0.023	0.12	-9999	-0.51	32	32
WNT4	-0.019	0.12	-9999	-0.5	29	29
NFAT1/CK1 alpha	-0.048	0.097	-9999	-0.42	15	15
GNG2	0.008	0.032	-9999	-0.5	2	2
WNT5A	0.004	0.055	-9999	-0.5	6	6
WNT11	-0.057	0.17	-9999	-0.5	67	67
CDC42	-0.014	0.11	-9999	-0.41	14	14

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.002	0.02	0.19	3	-10000	0	3
RFC1	0.002	0.02	0.21	1	-10000	0	1
PRKDC	0.002	0.02	0.19	3	-10000	0	3
RIPK1	0.011	0.004	-10000	0	-10000	0	0
CASP7	-0.016	0.04	0.23	2	-0.5	1	3
FASLG/FAS/FADD/FAF1	0.006	0.075	0.21	37	-0.26	10	47
MAP2K4	-0.026	0.13	-10000	0	-0.46	7	7
mol:ceramide	-0.01	0.091	-10000	0	-0.37	10	10
GSN	0.002	0.02	0.21	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 8	0.011	0.077	0.29	1	-0.33	8	9
FAS	0.002	0.055	-10000	0	-0.5	6	6
BID	0.001	0.023	0.28	2	-0.3	1	3
MAP3K1	-0.007	0.082	0.19	2	-0.29	7	9
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.002	0.02	0.21	1	-10000	0	1
CFLAR	0.011	0.004	-10000	0	-10000	0	0
HGF/MET	-0.067	0.15	-10000	0	-0.35	99	99
ARHGDIB	0.002	0.02	0.19	3	-10000	0	3
FADD	0.008	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.02	-10000	0	-0.21	1	1
NFKB1	-0.048	0.085	-10000	0	-0.25	7	7
MAPK8	-0.058	0.2	-10000	0	-0.42	121	121
DFFA	0.002	0.02	0.19	3	-0.2	1	4
DNA fragmentation during apoptosis	0.002	0.02	0.19	3	-10000	0	3
FAS/FADD/MET	-0.023	0.081	-10000	0	-0.3	39	39
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.007	0.045	-10000	0	-0.5	4	4
FAF1	0.008	0.005	-10000	0	-10000	0	0
PARP1	0.002	0.02	0.21	1	-10000	0	1
DFFB	0.002	0.02	0.19	3	-10000	0	3
CHUK	-0.042	0.075	-10000	0	-0.23	6	6
FASLG	0.002	0.056	-10000	0	-0.51	6	6
FAS/FADD	-0.006	0.039	-10000	0	-0.36	6	6
HGF	-0.021	0.12	-10000	0	-0.5	31	31
LMNA	0.002	0.018	0.2	1	-10000	0	1
CASP6	0.002	0.02	0.19	3	-10000	0	3
CASP10	0.006	0.032	-10000	0	-0.51	2	2
CASP3	0.002	0.024	0.21	5	-0.23	1	6
PTPN13	-0.044	0.16	-10000	0	-0.5	54	54
CASP8	0.001	0.03	0.36	2	-0.36	1	3
IL6	-0.25	0.51	-10000	0	-1.2	120	120
MET	-0.024	0.13	-10000	0	-0.5	34	34
ICAD/CAD	0.002	0.019	0.2	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.01	0.092	-10000	0	-0.38	10	10
activation of caspase activity by cytochrome c	0.001	0.023	0.28	2	-0.3	1	3
PAK2	0.002	0.02	0.21	1	-10000	0	1
BCL2	0.007	0.039	-10000	0	-0.5	3	3

×

LPA receptor mediated 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
GNB1/GNG2	-0.002	0.021	-9999	-0.26	3	3
NF kappa B1 p50/RelA/I kappa B alpha	-0.025	0.069	-9999	-0.36	3	3
AP1	-0.036	0.086	-9999	-0.45	5	5
mol:PIP3	-0.028	0.073	-9999	-0.41	4	4
AKT1	-0.002	0.016	-9999	-10000	0	0
PTK2B	0.018	0.032	-9999	-0.27	2	2
RHOA	0.024	0.024	-9999	-10000	0	0
PIK3CB	0.009	0	-9999	-10000	0	0
mol:Ca2+	0.004	0.085	-9999	-0.37	4	4
MAGI3	0.004	0.055	-9999	-0.5	6	6
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.006	0.085	-9999	-0.25	52	52
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.015	0.064	-9999	-0.26	10	10
NF kappa B1 p50/RelA	-0.026	0.071	-9999	-0.36	3	3
endothelial cell migration	0.021	0.024	-9999	-0.36	2	2
ADCY4	0.012	0.068	-9999	-0.36	6	6
ADCY5	-0.003	0.085	-9999	-0.3	20	20
ADCY6	0.019	0.053	-9999	-0.35	2	2
ADCY7	0.019	0.054	-9999	-0.35	2	2
ADCY1	0.017	0.057	-9999	-0.32	4	4
ADCY2	0.002	0.079	-9999	-0.32	11	11
ADCY3	0.02	0.053	-9999	-0.35	2	2
ADCY8	-0.052	0.1	-9999	-0.3	23	23
ADCY9	0.016	0.062	-9999	-0.33	6	6
GSK3B	0.023	0.031	-9999	-0.25	2	2
arachidonic acid secretion	0.023	0.05	-9999	-0.32	2	2
GNG2	0.008	0.032	-9999	-0.5	2	2
TRIP6	0.017	0.029	-9999	-0.36	3	3
GNAO1	0.017	0.04	-9999	-0.29	8	8
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	0.011	0.096	-9999	-0.42	3	3
GAB1	0.008	0.032	-9999	-0.5	2	2
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.025	0.15	-9999	-0.86	15	15
JUN	0.007	0.039	-9999	-0.5	3	3
LPA/LPA2/NHERF2	-0.004	0.032	-9999	-0.3	6	6
TIAM1	-0.029	0.17	-9999	-1	15	15
PIK3R1	0.008	0.022	-9999	-0.5	1	1
mol:IP3	0.004	0.086	-9999	-0.38	4	4
PLCB3	0.019	0.031	-9999	-0.26	6	6
FOS	-0.017	0.11	-9999	-0.5	27	27
positive regulation of mitosis	0.023	0.05	-9999	-0.32	2	2
LPA/LPA1-2-3	-0.029	0.081	-9999	-0.26	57	57
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.009	0.022	-9999	-0.5	1	1
stress fiber formation	0.016	0.052	-9999	-10000	0	0
GNAZ	-0.004	0.086	-9999	-0.29	42	42
EGFR/PI3K-beta/Gab1	-0.029	0.075	-9999	-0.43	4	4
positive regulation of dendritic cell cytokine production	-0.029	0.08	-9999	-0.26	57	57
LPA/LPA2/MAGI-3	-0.004	0.034	-9999	-0.3	7	7
ARHGEF1	0.03	0.018	-9999	-10000	0	0
GNAI2	0.021	0.016	-9999	-0.29	1	1
GNAI3	0.021	0.016	-9999	-0.29	1	1
GNAI1	0.02	0.025	-9999	-0.29	3	3
LPA/LPA3	-0.038	0.11	-9999	-0.36	55	55
LPA/LPA2	-0.001	0.016	-9999	-0.36	1	1
LPA/LPA1	-0.001	0.018	-9999	-0.29	2	2
HB-EGF/EGFR	-0.11	0.18	-9999	-0.33	189	189
HBEGF	-0.12	0.2	-9999	-0.38	185	185
mol:DAG	0.004	0.086	-9999	-0.38	4	4
cAMP biosynthetic process	0.006	0.063	-9999	-0.36	2	2
NFKB1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
GNB1	0.009	0	-9999	-10000	0	0
LYN	0.011	0.096	-9999	-0.42	3	3
GNAQ	-0.011	0.088	-9999	-0.26	51	51
LPAR2	0.009	0.023	-9999	-0.51	1	1
LPAR3	-0.045	0.16	-9999	-0.5	55	55
LPAR1	0.012	0.023	-9999	-0.49	1	1
IL8	-0.041	0.14	-9999	-0.4	29	29
PTK2	0.002	0.083	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.007	0.085	-9999	-0.25	52	52
EGFR	-0.006	0.089	-9999	-0.5	16	16
PLCG1	-0.008	0.097	-9999	-0.28	52	52
PLD2	0.002	0.083	-9999	-10000	0	0
G12/G13	-0.001	0.013	-9999	-0.26	1	1
PI3K-beta	-0.003	0.018	-9999	-10000	0	0
cell migration	-0.016	0.049	-9999	-0.25	15	15
SLC9A3R2	0.005	0.05	-9999	-0.5	5	5
PXN	0.016	0.053	-9999	-10000	0	0
HRAS/GTP	0.023	0.051	-9999	-0.32	2	2
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.1	0.21	-9999	-0.51	112	112
PRKCE	0.004	0.055	-9999	-0.5	6	6
PRKCD	0.01	0.083	-9999	-0.39	3	3
Gi(beta/gamma)	0.021	0.053	-9999	-0.33	2	2
mol:LPA	0.003	0.007	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.023	0.064	-9999	-10000	0	0
MAPKKK cascade	0.023	0.05	-9999	-0.32	2	2
contractile ring contraction involved in cytokinesis	0.024	0.024	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.018	0.098	-9999	-0.27	63	63
GNA15	-0.01	0.085	-9999	-0.26	51	51
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	0.015	0.065	-9999	-0.26	10	10
GNA11	-0.011	0.09	-9999	-0.27	52	52
Rac1/GTP	-0.026	0.16	-9999	-0.92	15	15
MMP2	0.021	0.024	-9999	-0.36	2	2

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.019	0.085	-10000	0	-0.41	5	5
IKBKB	-0.004	0.047	-10000	0	-0.24	4	4
AKT1	-0.033	0.08	-10000	0	-0.26	4	4
IKBKG	-0.002	0.049	-10000	0	-0.24	5	5
CALM1	-0.015	0.078	0.23	1	-0.59	5	6
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.039	0.11	-10000	0	-0.56	4	4
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.022	0.083	0.2	5	-0.63	5	10
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.005	0.056	0.15	3	-0.25	6	9
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.008	0.032	-10000	0	-0.5	2	2
SHC1	0.008	0.032	-10000	0	-0.51	2	2
BCR complex	-0.082	0.16	-10000	0	-0.38	110	110
CD22	-0.052	0.11	-10000	0	-0.55	11	11
CAMK2G	-0.009	0.073	0.22	1	-0.54	5	6
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	3	3
SHC/GRB2/SOS1	-0.05	0.099	-10000	0	-0.43	12	12
GO:0007205	-0.023	0.084	0.2	5	-0.65	5	10
SYK	0.007	0.039	-10000	0	-0.5	3	3
ELK1	-0.016	0.08	0.2	5	-0.6	5	10
NFATC1	-0.06	0.12	-10000	0	-0.39	16	16
B-cell antigen/BCR complex	-0.082	0.16	-10000	0	-0.38	110	110
PAG1/CSK	-0.001	0.016	-10000	0	-0.35	1	1
NFKBIB	0.006	0.019	0.066	1	-10000	0	1
HRAS	-0.015	0.078	0.21	1	-0.54	5	6
NFKBIA	0.006	0.018	0.066	1	-10000	0	1
NF-kappa-B/RelA/I kappa B beta	0.01	0.015	-10000	0	-10000	0	0
RasGAP/Csk	-0.056	0.11	-10000	0	-0.5	10	10
mol:GDP	-0.023	0.082	0.24	1	-0.63	5	6
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	0	0.071	-10000	0	-0.51	10	10
NF-kappa-B/RelA/I kappa B alpha	0.01	0.015	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.07	0.13	-10000	0	-0.61	5	5
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
mol:IP3	-0.028	0.084	0.2	5	-0.66	5	10
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.021	0.092	0.22	1	-0.46	10	11
CHUK	-0.002	0.049	-10000	0	-0.26	4	4
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.033	0.075	-10000	0	-0.5	6	6
PTPN6	-0.048	0.099	-10000	0	-0.51	11	11
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.009	0.021	-10000	0	-0.089	15	15
VAV2	-0.12	0.15	-10000	0	-0.36	107	107
ubiquitin-dependent protein catabolic process	0.009	0.018	0.068	1	-10000	0	1
BTK	-0.072	0.26	0.32	1	-1	35	36
CD19	-0.14	0.17	-10000	0	-0.41	107	107
MAP4K1	0.005	0.05	-10000	0	-0.5	5	5
CD72	0.009	0.022	-10000	0	-0.5	1	1
PAG1	0.009	0.022	-10000	0	-0.5	1	1
MAPK14	-0.029	0.1	-10000	0	-0.47	4	4
SH3BP5	0.004	0.055	-10000	0	-0.5	6	6
PIK3AP1	-0.017	0.1	0.21	4	-0.52	13	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.013	0.11	-10000	0	-0.79	6	6
RAF1	-0.008	0.074	0.21	1	-0.5	5	6
RasGAP/p62DOK/SHIP	-0.054	0.11	-10000	0	-0.47	11	11
CD79A	-0.1	0.21	-10000	0	-0.51	109	109
re-entry into mitotic cell cycle	-0.005	0.055	0.15	3	-0.25	6	9
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.005	0.064	-10000	0	-0.41	5	5
MAPK1	0.005	0.064	-10000	0	-0.41	5	5
CD72/SHP1	-0.018	0.1	-10000	0	-0.47	11	11
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.029	0.1	-10000	0	-0.52	3	3
actin cytoskeleton organization	-0.079	0.15	-10000	0	-0.31	107	107
NF-kappa-B/RelA	0.025	0.028	0.13	1	-10000	0	1
Calcineurin	-0.021	0.057	-10000	0	-0.48	5	5
PI3K	-0.1	0.12	-10000	0	-0.42	14	14
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.028	0.082	0.22	4	-0.68	5	9
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.011	0.098	-10000	0	-0.69	6	6
DAPP1	-0.03	0.093	-10000	0	-0.85	4	4
cytokine secretion	-0.056	0.12	-10000	0	-0.37	16	16
mol:DAG	-0.028	0.084	0.2	5	-0.66	5	10
PLCG2	0.007	0.039	-10000	0	-0.5	3	3
MAP2K1	-0.002	0.069	0.2	1	-0.46	5	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.069	0.14	-10000	0	-0.32	110	110
mol:PI-3-4-5-P3	-0.077	0.092	-10000	0	-0.3	13	13
ETS1	-0.003	0.069	0.22	1	-0.46	6	7
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.058	0.12	-10000	0	-0.5	12	12
B-cell antigen/BCR complex/LYN	-0.042	0.091	-10000	0	-0.41	11	11
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.084	0.15	-10000	0	-0.33	107	107
B-cell antigen/BCR complex/LYN/SYK	-0.058	0.11	-10000	0	-0.41	20	20
CARD11	-0.03	0.099	0.23	1	-0.49	10	11
FCGR2B	0.009	0.022	-10000	0	-0.5	1	1
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.003	0.024	-10000	0	-0.092	2	2
PTPRC	-0.007	0.091	-10000	0	-0.5	17	17
PDPK1	-0.035	0.079	-10000	0	-0.21	11	11
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.011	0.012	-10000	0	-0.1	1	1

×

Caspase cascade in apoptosis

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
TOP1	0.003	0.084	-10000	0	-0.29	36	36
ACTA1	-0.007	0.1	-10000	0	-0.36	36	36
NUMA1	0.003	0.084	-10000	0	-0.29	35	35
SPTAN1	-0.004	0.1	-10000	0	-0.36	36	36
LIMK1	-0.004	0.1	-10000	0	-0.36	36	36
BIRC3	0.003	0.06	-10000	0	-0.5	7	7
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	-0.003	0.095	-10000	0	-0.33	38	38
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.003	0.084	-10000	0	-0.29	35	35
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.1	-10000	0	-0.35	36	36
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.008	0.032	-10000	0	-0.5	2	2
GSN	-0.004	0.1	-10000	0	-0.36	36	36
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.038	0.12	-10000	0	-0.66	18	18
BID	0.004	0.057	-10000	0	-0.32	5	5
MAP3K1	0.004	0.037	-10000	0	-0.21	4	4
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0.002	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.004	0.1	-10000	0	-0.36	36	36
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.002	0.028	-10000	0	-10000	0	0
neuron apoptosis	0.017	0.021	-10000	0	-0.35	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.1	-10000	0	-0.34	35	35
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.016	0.054	-10000	0	-0.32	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.002	0.1	-10000	0	-0.34	35	35
CASP7	-0.005	0.028	0.29	2	-10000	0	2
KRT18	0.011	0.017	-10000	0	-10000	0	0
apoptosis	0.006	0.09	-10000	0	-0.52	6	6
DFFA	-0.004	0.1	-10000	0	-0.36	36	36
DFFB	-0.004	0.1	-10000	0	-0.36	36	36
PARP1	0.002	0.029	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.096	0.33	35	-10000	0	35
TNF	-0.009	0.096	-10000	0	-0.5	19	19
CYCS	0.007	0.041	-10000	0	-0.22	5	5
SATB1	0.016	0.066	-10000	0	-0.41	3	3
SLK	-0.004	0.1	-10000	0	-0.36	36	36
p15 BID/BAX	0.009	0.051	-10000	0	-0.28	5	5
CASP2	0.03	0.043	-10000	0	-10000	0	0
JNK cascade	-0.004	0.037	0.21	4	-10000	0	4
CASP3	-0.011	0.11	-10000	0	-0.38	36	36
LMNB2	0.029	0.038	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.004	0.03	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.037	0.12	-10000	0	-0.65	18	18
stress fiber formation	-0.004	0.1	-10000	0	-0.35	36	36
GZMB	-0.011	0.11	-10000	0	-0.4	36	36
CASP1	0.01	0.035	-10000	0	-0.31	6	6
LMNB1	0.028	0.039	-10000	0	-10000	0	0
APP	0.017	0.021	-10000	0	-0.35	1	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.016	-10000	0	-0.36	1	1
VIM	0.002	0.089	-10000	0	-0.3	35	35
LMNA	0.029	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.025	0.045	-10000	0	-10000	0	0
LRDD	0.008	0.032	-10000	0	-0.5	2	2
SREBF1	-0.004	0.1	-10000	0	-0.36	36	36
APAF-1/Caspase 9	-0.003	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.003	0.083	-10000	0	-0.29	35	35
CFL2	0.002	0.099	-10000	0	-0.34	35	35
GAS2	-0.017	0.12	-10000	0	-0.37	37	37
positive regulation of apoptosis	0.031	0.038	-10000	0	-10000	0	0
PRF1	-0.013	0.1	-10000	0	-0.5	23	23

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.002	0.077	-9999	-0.5	12	12
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.052	0.11	-9999	-0.3	91	91
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.024	0.11	-9999	-0.52	1	1
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.003	0.067	-9999	-0.51	9	9
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	0	0.071	-9999	-0.51	10	10
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.009	0.056	-9999	-0.36	13	13
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.006	0.09	-9999	-0.51	16	16
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.13	0.23	-9999	-0.51	141	141
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.057	0.13	-9999	-0.32	91	91
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.038	0.11	-9999	-0.33	29	29
MAP1B	-0.002	0.019	-9999	-0.28	1	1
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.017	0.11	-9999	-0.58	2	2
RELN	-0.069	0.18	-9999	-0.5	79	79
PAFAH/LIS1	0.014	0.044	-9999	-0.3	10	10
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.047	0.072	-9999	-0.4	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.02	0.11	-9999	-0.36	18	18
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.046	0.12	-9999	-0.36	29	29
LIS1/IQGAP1	0.021	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	-0.014	0.11	-9999	-0.51	24	24
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.014	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.061	0.089	-9999	-0.49	2	2
LRP8	-0.003	0.081	-9999	-0.51	13	13
NDEL1/Katanin 60	-0.038	0.11	-9999	-0.52	2	2
P39/CDK5	-0.081	0.15	-9999	-0.48	29	29
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.016	0.1	-9999	-0.49	1	1
PPP2R5D	0.01	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.047	0.11	-9999	-0.49	9	9
RELN/VLDLR	-0.052	0.11	-9999	-0.28	97	97
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.009	0.022	-10000	0	-0.5	1	1
Jak2/Leptin Receptor	-0.039	0.094	0.18	1	-0.35	21	22
PTP1B/AKT1	0.01	0.037	-10000	0	-10000	0	0
FYN	0.009	0.022	-10000	0	-0.5	1	1
p210 bcr-abl/PTP1B	0.006	0.041	-10000	0	-0.23	2	2
EGFR	-0.007	0.089	-10000	0	-0.51	16	16
EGF/EGFR	-0.049	0.091	-10000	0	-0.29	25	25
CSF1	0.005	0.05	-10000	0	-0.5	5	5
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.01	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.019	0.093	-10000	0	-0.27	38	38
Insulin Receptor/Insulin	-0.007	0.021	-10000	0	-10000	0	0
HCK	-0.014	0.11	-10000	0	-0.5	24	24
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	0.011	0.039	-10000	0	-0.23	1	1
EGF	-0.089	0.2	-10000	0	-0.5	99	99
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.092	0.099	-10000	0	-0.32	25	25
TXN	0.005	0.039	-10000	0	-0.5	3	3
PTP1B/IRS1/GRB2	0.016	0.039	-10000	0	-0.3	1	1
cell migration	-0.006	0.041	0.23	2	-10000	0	2
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.053	0.17	-10000	0	-0.5	62	62
ITGA2B	-0.044	0.16	-10000	0	-0.5	54	54
CSF1R	0.003	0.059	-10000	0	-0.5	7	7
Prolactin Receptor/Prolactin	-0.052	0.13	-10000	0	-0.37	74	74
FGR	-0.029	0.14	-10000	0	-0.5	39	39
PTP1B/p130 Cas	0.01	0.041	-10000	0	-0.25	2	2
Crk/p130 Cas	0.016	0.039	-10000	0	-0.26	1	1
DOK1	0.016	0.038	-10000	0	-0.25	1	1
JAK2	-0.005	0.064	-10000	0	-0.3	12	12
Jak2/Leptin Receptor/Leptin	-0.027	0.065	-10000	0	-0.41	5	5
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
PTPN1	0.006	0.041	-10000	0	-0.23	2	2
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.048	0.16	-10000	0	-0.51	58	58
SRC	0.015	0.018	-10000	0	-10000	0	0
ITGB3	-0.019	0.12	-10000	0	-0.51	28	28
CAT1/PTP1B	-0.031	0.13	-10000	0	-0.48	24	24
CAPN1	0.01	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.003	0.02	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.022	0.063	-10000	0	-0.42	5	5
negative regulation of transcription	-0.005	0.063	-10000	0	-0.3	12	12
FCGR2A	0.002	0.063	-10000	0	-0.5	8	8
FER	0.008	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.056	0.13	-10000	0	-0.36	81	81
BLK	-0.08	0.2	-10000	0	-0.51	89	89
Insulin Receptor/Insulin/Shc	-0.001	0.019	-10000	0	-0.31	2	2
RHOA	0.01	0.001	-10000	0	-10000	0	0
LEPR	-0.047	0.16	-10000	0	-0.5	57	57
BCAR1	0.009	0.022	-10000	0	-0.5	1	1
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.039	0.14	-10000	0	-0.49	28	28
PRL	-0.01	0.08	-10000	0	-0.51	13	13
SOCS3	0.001	0.11	-10000	0	-1.2	4	4
SPRY2	0.006	0.032	-10000	0	-0.5	2	2
Insulin Receptor/Insulin/IRS1	-0.001	0.013	-10000	0	-0.3	1	1
CSF1/CSF1R	0.01	0.06	-10000	0	-0.36	6	6
Ras protein signal transduction	0.01	0.014	-10000	0	-10000	0	0
IRS1	0.009	0.022	-10000	0	-0.5	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.044	0.16	-10000	0	-0.51	52	52
STAT5B	0.004	0.044	-10000	0	-0.23	2	2
STAT5A	0.003	0.045	-10000	0	-0.23	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.041	-10000	0	-0.26	2	2
CSN2	-0.014	0.044	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	0.007	0.06	-10000	0	-0.45	8	8
YBX1	0.015	0.001	-10000	0	-10000	0	0
LCK	0.007	0.039	-10000	0	-0.5	3	3
SHC1	0.008	0.032	-10000	0	-0.51	2	2
NOX4	-0.008	0.089	-10000	0	-0.5	16	16

×

Signaling events mediated by HDAC Class III

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	0.01	0	-10000	0	-10000	0	0
HDAC4	0.009	0.023	-10000	0	-0.51	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.003	0.083	0.36	26	-10000	0	26
CDKN1A	-0.001	0.03	-10000	0	-0.68	1	1
KAT2B	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.009	0.022	-10000	0	-0.5	1	1
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
TAT	-0.038	0.15	-10000	0	-0.51	47	47
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.007	0.028	-10000	0	-0.36	3	3
PPARGC1A	-0.12	0.22	-10000	0	-0.5	127	127
FHL2	-0.056	0.17	-10000	0	-0.51	65	65
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.006	-10000	0	-10000	0	0
HIST2H4A	-0.003	0.083	-10000	0	-0.36	26	26
SIRT1/FOXO3a	0	0.006	-10000	0	-10000	0	0
SIRT1	0	0.008	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.014	-10000	0	-0.3	1	1
SIRT1/Histone H1b	-0.009	0.032	-10000	0	-10000	0	0
apoptosis	0	0.006	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.074	0.13	-10000	0	-0.3	127	127
p53/SIRT1	0.001	0.017	0.38	1	-10000	0	1
SIRT1/FOXO4	0	0.006	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.034	0.091	-10000	0	-0.27	66	66
HIST1H1E	0.004	0.044	-10000	0	-10000	0	0
SIRT1/p300	0	0.006	-10000	0	-10000	0	0
muscle cell differentiation	0.001	0.023	0.3	3	-10000	0	3
TP53	0	0.008	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.006	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
MEF2D	0.01	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.033	0.1	-10000	0	-0.36	47	47
ACSS2	0.015	0.017	-10000	0	-0.35	1	1
SIRT1/PCAF/MYOD	-0.001	0.024	-10000	0	-0.3	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.009	0.056	-9999	-0.36	13	13
PDGFRB	0.008	0.023	-9999	-0.5	1	1
SPHK1	-0.009	0.02	-9999	-10000	0	0
mol:S1P	-0.011	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	-0.011	0.13	-9999	-0.35	49	49
GNAO1	0.003	0.06	-9999	-0.51	7	7
PDGFB-D/PDGFRB/PLCgamma1	-0.003	0.12	-9999	-0.44	11	11
PLCG1	-0.006	0.13	-9999	-0.34	47	47
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.023	-9999	-0.5	1	1
GNAI2	0.01	0.003	-9999	-10000	0	0
GNAI3	0.01	0.003	-9999	-10000	0	0
GNAI1	0.008	0.032	-9999	-0.51	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.005	0.051	-9999	-0.31	13	13
S1P1/S1P	-0.019	0.053	-9999	-0.32	7	7
negative regulation of cAMP metabolic process	-0.01	0.13	-9999	-0.35	49	49
MAPK3	-0.02	0.18	-9999	-0.53	47	47
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.004	0.081	-9999	-0.5	13	13
PLCB2	0.01	0.07	-9999	-0.33	9	9
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.016	0.045	-9999	-0.3	5	5
receptor internalization	-0.019	0.051	-9999	-0.3	7	7
PTGS2	-0.058	0.3	-9999	-0.98	47	47
Rac1/GTP	-0.016	0.045	-9999	-0.3	5	5
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.009	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.01	0.13	-9999	-0.35	49	49
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.031	0.14	-9999	-0.5	41	41
MAPK1	-0.02	0.18	-9999	-0.53	47	47
S1P1/S1P/PDGFB-D/PDGFRB	0.012	0.073	-9999	-0.34	7	7
ABCC1	0.01	0.002	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.18	0.25	-10000	0	-0.51	190	190
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.008	0.032	-10000	0	-0.5	2	2
CDKN1A	0.018	0.04	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	-0.001	0.022	-10000	0	-0.36	2	2
mol:Ca2+	-0.06	0.14	0.2	2	-0.37	85	87
AGT	-0.076	0.19	-10000	0	-0.51	85	85
CCNA2	-0.044	0.14	-10000	0	-0.49	14	14
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	-0.001	0.083	-10000	0	-0.35	28	28
CDK2/Cyclin E1	-0.07	0.14	-10000	0	-0.36	18	18
MAPK3	0.016	0.023	-10000	0	-0.36	2	2
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.023	-10000	0	-0.36	2	2
PTP4A1	0.014	0.064	-10000	0	-10000	0	0
PTP4A3	0.008	0.032	-10000	0	-0.51	2	2
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.016	0.023	-10000	0	-0.36	2	2
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.019	0.03	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.017	0.06	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0	0.02	0.2	2	-0.36	1	3
RHOC	0.019	0.03	-10000	0	-10000	0	0
RHOA	0.019	0.03	-10000	0	-10000	0	0
cell motility	0.022	0.033	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.018	0.059	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.003	0.031	-10000	0	-0.36	4	4
ROCK1	0.022	0.033	-10000	0	-10000	0	0
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.014	0.063	-10000	0	-10000	0	0
ATF5	0.009	0.023	-10000	0	-0.51	1	1

×

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

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
MET/RANBP9	-0.023	0.088	-9999	-0.36	34	34
CRKL	0.004	0.081	-9999	-0.43	5	5
mol:PIP3	-0.016	0.005	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0.008	0.032	-9999	-0.5	2	2
RAPGEF1	0.01	0.077	-9999	-0.4	5	5
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.037	0.1	-9999	-0.31	62	62
MAP3K5	0.016	0.079	-9999	-0.44	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.033	0.091	-9999	-0.52	3	3
AP1	-0.024	0.078	-9999	-0.32	30	30
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.008	0.032	-9999	-0.51	2	2
apoptosis	-0.03	0.17	-9999	-0.71	30	30
STAT3 (dimer)	0.006	0.079	-9999	-0.39	4	4
GAB1/CRKL/SHP2/PI3K	-0.02	0.063	-9999	-0.44	4	4
INPP5D	0.007	0.039	-9999	-0.5	3	3
CBL/CRK	0.01	0.077	-9999	-0.49	3	3
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
ELK1	-0.011	0.047	-9999	-0.19	34	34
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.015	0.044	-9999	-0.25	4	4
PAK1	0.007	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.037	0.1	-9999	-0.31	62	62
HRAS	-0.011	0.13	-9999	-0.56	21	21
DOCK1	0.01	0.077	-9999	-0.49	3	3
GAB1	-0.002	0.085	-9999	-0.3	23	23
CRK	0.004	0.081	-9999	-0.4	6	6
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.045	0.14	-9999	-0.48	45	45
JUN	0.007	0.039	-9999	-0.5	3	3
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.024	0.067	-9999	-0.22	45	45
PIK3R1	0.009	0.022	-9999	-0.5	1	1
cell morphogenesis	0.026	0.087	-9999	-0.43	4	4
GRB2/SHC	-0.001	0.066	-9999	-0.32	5	5
FOS	-0.017	0.11	-9999	-0.5	27	27
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.011	0.047	-9999	-0.19	34	34
HGF/MET/MUC20	-0.038	0.1	-9999	-0.31	62	62
cell migration	-0.02	0.058	-9999	-0.31	5	5
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	-0.023	0.088	-9999	-0.36	34	34
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0	0.081	-9999	-0.41	4	4
MET/MUC20	-0.024	0.09	-9999	-0.36	34	34
RAP1B	0.016	0.073	-9999	-0.46	3	3
RAP1A	0.016	0.073	-9999	-0.46	3	3
HGF/MET/RANBP9	-0.037	0.1	-9999	-0.31	62	62
RAF1	-0.004	0.12	-9999	-0.52	21	21
STAT3	0.006	0.08	-9999	-0.4	4	4
cell proliferation	0.006	0.11	-9999	-0.33	45	45
RPS6KB1	0.001	0.028	-9999	-10000	0	0
MAPK3	-0.014	0.043	-9999	-0.18	15	15
MAPK1	-0.014	0.043	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.029	0.068	-9999	-0.38	3	3
SRC	0.007	0.076	-9999	-0.38	4	4
PI3K	0	0.065	-9999	-0.33	4	4
MET/Glomulin	-0.012	0.081	-9999	-0.32	34	34
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.003	0.12	-9999	-0.48	21	21
MET	-0.024	0.13	-9999	-0.5	34	34
MAP4K1	0.01	0.084	-9999	-0.4	8	8
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.003	0.12	-9999	-0.48	21	21
BAD	0.007	0.004	-9999	-10000	0	0
MAP2K4	0.021	0.074	-9999	-0.4	5	5
SHP2/GRB2/SOS1/GAB1	-0.025	0.078	-9999	-0.34	22	22
INPPL1	0.01	0	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
SH3KBP1	0.01	0	-9999	-10000	0	0
HGS	-0.005	0.066	-9999	-0.24	21	21
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.021	0.12	-9999	-0.5	31	31
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0
NCK/PLCgamma1	0.001	0.066	-9999	-0.33	3	3
PDPK1	-0.006	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.039	0.11	-9999	-0.32	62	62

×

TCR signaling in naïve CD8+ T cells

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.019	0.082	-10000	0	-0.51	11	11
FYN	0.03	0.13	-10000	0	-0.65	13	13
LAT/GRAP2/SLP76	-0.016	0.1	-10000	0	-0.52	16	16
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.037	0.092	-10000	0	-0.43	13	13
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	-0.008	0.023	-10000	0	-0.14	7	7
MAP3K8	0.008	0.032	-10000	0	-0.5	2	2
mol:Ca2+	-0.01	0.025	-10000	0	-0.11	14	14
integrin-mediated signaling pathway	-0.001	0.018	-10000	0	-0.3	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.034	0.13	-10000	0	-0.63	14	14
TRPV6	-0.072	0.18	-10000	0	-0.51	73	73
CD28	0.009	0.023	-10000	0	-0.51	1	1
SHC1	0.03	0.12	-10000	0	-0.58	14	14
receptor internalization	0.023	0.12	-10000	0	-0.56	15	15
PRF1	-0.014	0.25	-10000	0	-1.1	25	25
KRAS	0.008	0.032	-10000	0	-0.51	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.038	0.077	-10000	0	-0.36	13	13
LAT	0.03	0.12	-10000	0	-0.62	12	12
EntrezGene:6955	0	0.005	-10000	0	-10000	0	0
CD3D	0.008	0.04	-10000	0	-0.51	3	3
CD3E	0.006	0.052	-10000	0	-0.52	5	5
CD3G	0.001	0.071	-10000	0	-0.51	10	10
RASGRP2	0.002	0.04	-10000	0	-0.16	27	27
RASGRP1	0.036	0.1	-10000	0	-0.44	14	14
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.008	0.032	-10000	0	-0.5	2	2
RAP1A/GTP/RAPL	-0.001	0.019	-10000	0	-0.3	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.036	-10000	0	-0.12	12	12
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.041	-10000	0	-0.23	9	9
PRKCA	-0.005	0.051	-10000	0	-0.27	11	11
GRAP2	-0.006	0.088	-10000	0	-0.5	16	16
mol:IP3	0.01	0.11	0.21	63	-0.44	11	74
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.016	0.11	-10000	0	-0.59	11	11
ORAI1	0.041	0.099	0.28	73	-10000	0	73
CSK	0.03	0.12	-10000	0	-0.66	11	11
B7 family/CD28	-0.033	0.14	-10000	0	-0.67	17	17
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.024	0.14	-10000	0	-0.67	14	14
PTPN6	0.027	0.12	-10000	0	-0.64	12	12
VAV1	0.029	0.12	-10000	0	-0.62	14	14
Monovalent TCR/CD3	0.008	0.086	-10000	0	-0.38	17	17
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.028	0.13	-10000	0	-0.69	12	12
PAG1	0.029	0.12	-10000	0	-0.66	11	11
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.023	0.14	-10000	0	-0.73	12	12
CD80	-0.003	0.081	-10000	0	-0.5	13	13
CD86	0	0.071	-10000	0	-0.5	10	10
PDK1/CARD11/BCL10/MALT1	-0.017	0.05	-10000	0	-0.27	10	10
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.024	0.12	-10000	0	-0.55	17	17
CD8A	0.005	0.056	-10000	0	-0.51	6	6
CD8B	0.003	0.064	-10000	0	-0.51	8	8
PTPRC	-0.007	0.092	-10000	0	-0.5	17	17
PDK1/PKC theta	0.033	0.12	-10000	0	-0.48	18	18
CSK/PAG1	0.033	0.12	-10000	0	-0.66	10	10
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.016	0.007	-10000	0	-10000	0	0
GRAP2/SLP76	-0.02	0.12	-10000	0	-0.57	18	18
STIM1	0.021	0.049	-10000	0	-10000	0	0
RAS family/GTP	0.038	0.041	-10000	0	-0.17	7	7
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.022	0.13	-10000	0	-0.61	15	15
mol:DAG	-0.005	0.074	-10000	0	-0.37	13	13
RAP1A/GDP	0.013	0.016	-10000	0	-0.062	3	3
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.005	0.056	-10000	0	-0.51	6	6
cytotoxic T cell degranulation	-0.01	0.24	-10000	0	-1.1	25	25
RAP1A/GTP	-0.004	0.013	-10000	0	-0.059	27	27
mol:PI-3-4-5-P3	0.036	0.11	-10000	0	-0.51	14	14
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.007	0.12	0.23	62	-0.54	13	75
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.004	0.055	-10000	0	-0.5	6	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.015	0.1	-10000	0	-0.55	13	13
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	0.006	0.07	-10000	0	-0.45	11	11
CARD11	-0.02	0.12	-10000	0	-0.51	30	30
PRKCB	-0.008	0.065	-10000	0	-0.3	18	18
PRKCE	-0.006	0.054	-10000	0	-0.29	10	10
PRKCQ	0.025	0.14	-10000	0	-0.54	20	20
LCP2	0.007	0.039	-10000	0	-0.5	3	3
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.037	0.08	-10000	0	-0.36	13	13
IKK complex	0.036	0.033	-10000	0	-0.11	11	11
RAS family/GDP	-0.002	0.007	-10000	0	-0.068	2	2
MAP3K14	0.038	0.06	-10000	0	-0.27	12	12
PDPK1	0.039	0.088	-10000	0	-0.41	13	13
TCR/CD3/MHC I/CD8/Fyn	0.022	0.13	-10000	0	-0.7	12	12

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.01	0.057	-9999	-0.32	16	16
EFNA5	0.003	0.06	-9999	-0.5	7	7
FYN	0.008	0.055	-9999	-0.28	17	17
neuron projection morphogenesis	-0.01	0.057	-9999	-0.32	16	16
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.01	0.057	-9999	-0.32	16	16
EPHA5	-0.004	0.071	-9999	-0.51	10	10

×

IL1-mediated signaling events

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
UBC13/UEV1A	-0.001	0.022	-10000	0	-0.36	2	2
PRKCZ	0.007	0.039	-10000	0	-0.5	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.011	0.039	-10000	0	-0.26	1	1
IRAK/TOLLIP	0.02	0.022	-10000	0	-0.26	3	3
IKBKB	0.01	0	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.18	-10000	0	-0.36	178	178
IL1A	-0.15	0.24	-10000	0	-0.5	158	158
IL1B	-0.009	0.096	-10000	0	-0.35	37	37
IRAK/TRAF6/p62/Atypical PKCs	-0.003	0.025	-10000	0	-10000	0	0
IL1R2	-0.015	0.11	-10000	0	-0.51	25	25
IL1R1	0.008	0.032	-10000	0	-0.5	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.011	0.049	0.19	10	-0.38	1	11
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0.006	0.045	-10000	0	-0.5	4	4
MAP3K3	0.009	0.022	-10000	0	-0.5	1	1
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.048	0.018	-10000	0	-10000	0	0
JUN	0.025	0.049	-10000	0	-0.42	1	1
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.017	0.061	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.08	0.12	-10000	0	-0.33	4	4
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.073	0.11	-10000	0	-0.49	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.019	0.07	-10000	0	-0.52	1	1
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.022	0.046	-10000	0	-10000	0	0
IRAK1	0.015	0.024	-10000	0	-0.3	3	3
IL1RN/IL1R1	-0.007	0.049	-10000	0	-0.35	10	10
IRAK4	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.017	0.052	-10000	0	-0.39	1	1
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.019	0.07	-10000	0	-0.52	1	1
IL1 beta/IL1R2	-0.035	0.1	-10000	0	-0.31	59	59
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.017	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.015	0.054	-10000	0	-0.42	1	1
IRAK3	-0.004	0.083	-10000	0	-0.5	14	14
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.018	0.063	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.048	0.12	-10000	0	-0.46	1	1
IL1 alpha/IL1R1/IL1RAP	-0.091	0.14	-10000	0	-0.29	159	159
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.009	0.023	-10000	0	-0.51	1	1
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.013	0.026	-10000	0	-10000	0	0
IL1RAP	0.01	0	-10000	0	-10000	0	0
UBE2N	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.016	0.052	-10000	0	-0.39	1	1
CASP1	0.004	0.055	-10000	0	-0.5	6	6
IL1RN/IL1R2	-0.023	0.089	-10000	0	-0.37	32	32
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.018	0.064	-10000	0	-0.49	1	1
TMEM189-UBE2V1	0.002	0.032	-10000	0	-0.51	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.04	0.091	-10000	0	-0.39	2	2
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL1RN	0.002	0.063	-10000	0	-0.5	8	8
TRAF6/TAK1/TAB1/TAB2	-0.001	0.015	-10000	0	-0.24	2	2
MAP2K6	0.016	0.048	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.029	0.072	0.4	5	-10000	0	5
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.02	0.074	-10000	0	-0.3	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.003	0.06	-10000	0	-0.51	7	7
RhoA/GTP	-0.029	0.073	-10000	0	-0.41	5	5
negative regulation of cAMP metabolic process	-0.01	0.091	-10000	0	-0.25	36	36
GNAZ	-0.031	0.14	-10000	0	-0.5	41	41
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.024	0.13	-10000	0	-0.5	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.01	0.092	-10000	0	-0.26	36	36
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.037	0.1	-10000	0	-0.32	60	60
cell-cell adhesion	0.049	0.096	0.42	13	-10000	0	13
Ephrin B/EPHB2/RasGAP	-0.034	0.087	-10000	0	-0.49	2	2
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.008	0.032	-10000	0	-0.51	2	2
Ephrin B1/EPHB3	-0.006	0.044	-10000	0	-0.3	11	11
Ephrin B1/EPHB1	-0.037	0.1	-10000	0	-0.31	62	62
HRAS/GDP	-0.036	0.085	-10000	0	-0.48	5	5
Ephrin B/EPHB1/GRB7	-0.039	0.099	-10000	0	-0.54	6	6
Endophilin/SYNJ1	-0.006	0.091	-10000	0	-0.46	2	2
KRAS	0.008	0.032	-10000	0	-0.51	2	2
Ephrin B/EPHB1/Src	-0.036	0.094	-10000	0	-0.55	4	4
endothelial cell migration	-0.004	0.031	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.004	0.055	-10000	0	-0.5	6	6
PAK1	-0.002	0.095	-10000	0	-0.46	3	3
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.008	0.096	-10000	0	-0.47	4	4
DNM1	0.002	0.064	-10000	0	-0.51	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.008	0.099	-10000	0	-0.53	4	4
lamellipodium assembly	-0.049	0.096	-10000	0	-0.42	13	13
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.006	0.071	-10000	0	-0.43	5	5
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
EPHB2	-0.047	0.16	-10000	0	-0.51	56	56
EPHB3	0.002	0.064	-10000	0	-0.51	8	8
EPHB1	-0.051	0.17	-10000	0	-0.51	60	60
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.033	0.085	-10000	0	-0.39	10	10
Ephrin B/EPHB2	-0.035	0.089	-10000	0	-0.5	2	2
Ephrin B/EPHB3	-0.012	0.055	-10000	0	-0.27	12	12
JNK cascade	-0.031	0.12	-10000	0	-0.49	9	9
Ephrin B/EPHB1	-0.037	0.096	-10000	0	-0.27	61	61
RAP1/GDP	-0.027	0.073	-10000	0	-0.43	5	5
EFNB2	0.002	0.063	-10000	0	-0.5	8	8
EFNB3	0.004	0.055	-10000	0	-0.5	6	6
EFNB1	0.007	0.039	-10000	0	-0.5	3	3
Ephrin B2/EPHB1-2	-0.065	0.13	-10000	0	-0.3	113	113
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.048	0.096	-10000	0	-0.43	13	13
Rap1/GTP	-0.048	0.095	-10000	0	-0.42	13	13
axon guidance	-0.037	0.1	-10000	0	-0.32	60	60
MAPK3	0.018	0.064	-10000	0	-0.4	4	4
MAPK1	0.018	0.064	-10000	0	-0.38	5	5
Rac1/GDP	0.001	0.09	-10000	0	-0.45	5	5
actin cytoskeleton reorganization	-0.04	0.08	-10000	0	-0.36	13	13
CDC42/GDP	0.001	0.09	-10000	0	-0.45	5	5
PI3K	-0.004	0.032	-10000	0	-10000	0	0
EFNA5	0.003	0.06	-10000	0	-0.5	7	7
Ephrin B2/EPHB4	-0.005	0.037	-10000	0	-0.3	8	8
Ephrin B/EPHB2/Intersectin/N-WASP	0.005	0.063	-10000	0	-0.41	2	2
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.048	0.095	-10000	0	-0.42	13	13
PTK2	0.014	0.028	-10000	0	-10000	0	0
MAP4K4	-0.031	0.12	-10000	0	-0.49	9	9
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.007	0.039	-10000	0	-0.5	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.009	0.094	-10000	0	-0.36	6	6
MAP2K1	0.012	0.067	-10000	0	-0.4	5	5
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.061	0.12	-10000	0	-0.53	9	9
cell migration	0.018	0.071	-10000	0	-0.43	5	5
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.007	0.092	-10000	0	-0.47	2	2
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.066	0.14	-10000	0	-0.46	20	20
HRAS/GTP	-0.053	0.1	-10000	0	-0.45	13	13
Ephrin B1/EPHB1-2	-0.062	0.12	-10000	0	-0.29	110	110
cell adhesion mediated by integrin	0.002	0.052	0.27	13	-10000	0	13
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.057	0.11	-10000	0	-0.48	13	13
RAC1-CDC42/GTP	-0.051	0.097	-10000	0	-0.41	14	14
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.027	0.073	-10000	0	-0.43	5	5
ruffle organization	-0.011	0.12	-10000	0	-0.42	13	13
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.004	0.095	-10000	0	-0.45	4	4
Ephrin B/EPHB2/KALRN	-0.036	0.089	-10000	0	-0.49	3	3
ROCK1	0.014	0.041	-10000	0	-0.27	11	11
RAS family/GDP	-0.038	0.076	-10000	0	-0.35	13	13
Rac1/GTP	-0.051	0.1	-10000	0	-0.44	13	13
Ephrin B/EPHB1/Src/Paxillin	0.004	0.071	-10000	0	-0.47	4	4

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	-0.001	0.013	-9999	-0.3	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.007	0.092	-9999	-0.51	17	17
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.005	0.043	-9999	-0.2	5	5
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.009	0.022	-9999	-0.5	1	1
FYN	0.009	0.022	-9999	-0.5	1	1
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	39	39
p38 alpha/TAB1	-0.016	0.051	-9999	-0.27	11	11
PRKG1	-0.056	0.17	-9999	-0.5	66	66
DUSP8	0	0.07	-9999	-0.5	10	10
PGK/cGMP/p38 alpha	-0.039	0.098	-9999	-0.37	28	28
apoptosis	-0.015	0.049	-9999	-0.26	11	11
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	-0.038	0.15	-9999	-0.5	48	48
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.011	-9999	-0.26	1	1
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	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	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.008	0.093	-9999	-0.36	20	20
BLK	-0.08	0.2	-9999	-0.51	89	89
HCK	-0.014	0.11	-9999	-0.5	24	24
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.008	0.032	-9999	-0.5	2	2
TRAF6/MEKK3	-0.001	0.012	-9999	-0.27	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.016	0.067	-9999	-0.3	11	11
positive regulation of innate immune response	0.013	0.098	-9999	-0.38	20	20
LCK	0.007	0.039	-9999	-0.5	3	3
p38alpha-beta/MKP7	0.017	0.094	-9999	-0.36	19	19
p38alpha-beta/MKP5	0.017	0.098	-9999	-0.37	20	20
PGK/cGMP	-0.046	0.12	-9999	-0.36	66	66
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.003	0.12	-9999	-0.4	24	24
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	-0.058	0.17	-9999	-0.51	67	67

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.008	0.041	-9999	-0.31	5	5
NFATC2	-0.003	0.072	-9999	-0.31	23	23
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.03	0.22	-9999	-0.71	24	24
PTGS2	-0.044	0.24	-9999	-0.66	34	34
JUNB	0.007	0.039	-9999	-0.5	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.009	-9999	-10000	0	0
CALM1	0.009	0.007	-9999	-10000	0	0
JUN	0.006	0.04	-9999	-0.5	3	3
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.011	0.1	-9999	-0.51	21	21
CREM	0.009	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.049	0.096	-9999	-0.47	13	13
FOS	-0.018	0.12	-9999	-0.51	27	27
IFNG	-0.037	0.23	-9999	-0.63	38	38
AP-1/NFAT1-c-4	-0.1	0.18	-9999	-0.64	31	31
FASLG	-0.022	0.2	-9999	-0.64	21	21
NFAT1-c-4/ICER1	-0.032	0.072	-9999	-0.39	12	12
IL2RA	-0.034	0.22	-9999	-0.62	32	32
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.041	0.23	-9999	-0.67	33	33
JunB/Fra1/NFAT1-c-4	-0.04	0.086	-9999	-0.42	11	11
IL4	-0.024	0.19	-9999	-0.61	20	20
IL2	-0.001	0.01	-9999	-10000	0	0
IL3	-0.01	0.016	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
BATF3	0.01	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.01	0.001	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.014	0.005	-9999	-10000	0	0
RAS family/GTP	-0.042	0.079	-9999	-0.33	2	2
NFATC4	-0.009	0.089	-9999	-0.35	2	2
ERBB2IP	0.01	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.049	0.093	-9999	-0.42	1	1
JUN	0.02	0.062	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	-0.019	0.1	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.057	0.11	-9999	-0.28	22	22
AKT1	0.008	0.003	-9999	-10000	0	0
BAD	0.015	0.002	-9999	-10000	0	0
MAPK10	-0.041	0.071	-9999	-0.27	24	24
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.028	0.11	-9999	-0.45	1	1
RAF1	0	0.098	-9999	-0.3	2	2
ErbB2/ErbB3/neuregulin 2	-0.034	0.089	-9999	-0.27	64	64
STAT3	0.001	0.002	-9999	-10000	0	0
cell migration	-0.004	0.079	-9999	-0.22	24	24
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.004	0.16	-9999	-0.54	24	24
FOS	-0.001	0.15	-9999	-0.44	40	40
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	-0.049	0.093	-9999	-0.42	1	1
MAPK3	0	0.14	-9999	-0.51	13	13
MAPK1	0	0.14	-9999	-0.51	13	13
JAK2	-0.02	0.1	-9999	-0.4	2	2
NF2	-0.002	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.035	0.11	-9999	-0.24	112	112
NRG1	-0.1	0.21	-9999	-0.5	111	111
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.021	0.11	-9999	-0.25	14	14
MAPK9	-0.024	0.046	-9999	-0.2	1	1
ERBB2	-0.002	0.028	-9999	-0.37	3	3
ERBB3	0.006	0.032	-9999	-0.5	2	2
SHC1	0.008	0.032	-9999	-0.51	2	2
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	0.001	0.007	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.003	-9999	-10000	0	0
RNF41	0.017	0.009	-9999	-10000	0	0
FRAP1	0.007	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.034	0.063	-9999	-0.28	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.023	-9999	-0.31	3	3
CHRNA1	0	0.14	-9999	-0.49	21	21
myelination	-0.007	0.088	-9999	-0.32	2	2
PPP3CB	-0.018	0.097	-9999	-0.37	1	1
KRAS	0.008	0.032	-9999	-0.51	2	2
RAC1-CDC42/GDP	-0.042	0.085	-9999	-0.32	2	2
NRG2	-0.049	0.16	-9999	-0.5	59	59
mol:GDP	-0.035	0.11	-9999	-0.24	112	112
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.007	0.097	-9999	-0.31	7	7
SRC	0.01	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.001	-9999	-10000	0	0
PTPN11	-0.02	0.1	-9999	-0.4	1	1
MAP2K1	-0.014	0.14	-9999	-0.5	13	13
heart morphogenesis	-0.049	0.093	-9999	-0.42	1	1
RAS family/GDP	-0.042	0.081	-9999	-0.34	2	2
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.012	0.02	-9999	-0.16	3	3
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.008	0.003	-9999	-10000	0	0
nervous system development	-0.049	0.093	-9999	-0.42	1	1
CDC42	0.01	0	-9999	-10000	0	0

×

BARD1 signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.002	0.027	-10000	0	-0.36	3	3
ATM	0.01	0	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.019	0.015	-10000	0	-10000	0	0
protein ubiquitination	-0.091	0.12	-10000	0	-0.49	4	4
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.01	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.006	0.02	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.007	0.039	-10000	0	-0.51	3	3
CCNE1	-0.18	0.25	-10000	0	-0.51	190	190
CDK2/Cyclin E1	-0.13	0.17	-10000	0	-0.36	190	190
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.038	-10000	0	-0.36	6	6
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	-0.011	0.1	-10000	0	-0.51	21	21
DNA repair	-0.014	0.12	-10000	0	-0.39	13	13
BRCA1/BARD1/ubiquitin	-0.004	0.038	-10000	0	-0.36	6	6
BARD1/DNA-PK	-0.002	0.02	-10000	0	-0.26	3	3
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.002	0.027	0.35	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.03	0.018	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.003	0.032	-10000	0	-0.3	6	6
BRCA1/BARD1/P53	-0.003	0.028	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.003	0.032	-10000	0	-0.3	6	6
BRCA1/BACH1	0.007	0.039	-10000	0	-0.51	3	3
BARD1	0.007	0.039	-10000	0	-0.5	3	3
PCNA	0.008	0.032	-10000	0	-0.51	2	2
BRCA1/BARD1/UbcH5C	-0.003	0.032	-10000	0	-0.3	6	6
BRCA1/BARD1/UbcH7	-0.003	0.032	-10000	0	-0.3	6	6
BRCA1/BARD1/RAD51/PCNA	-0.048	0.11	-10000	0	-0.53	5	5
BARD1/DNA-PK/P53	-0.001	0.018	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.038	-10000	0	-0.36	6	6
BRCA1/BARD1/CTIP	-0.003	0.028	-10000	0	-0.26	6	6
FA complex	0.026	0.029	-10000	0	-10000	0	0
BARD1/EWS	-0.002	0.027	-10000	0	-0.36	3	3
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.028	-10000	0	-10000	0	0
BRCA1/BARD1	-0.092	0.12	-10000	0	-0.5	4	4
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.002	0.028	-10000	0	-0.36	3	3
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.077	0.19	-10000	0	-0.51	86	86
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.038	-10000	0	-0.36	6	6
EWSR1	0.01	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.005	0.05	-9999	-0.5	5	5
ELF1	0.001	0.057	-9999	-0.33	1	1
CCNA2	-0.11	0.22	-9999	-0.51	119	119
PIK3CA	0.01	0	-9999	-10000	0	0
JAK3	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
JAK1	0.01	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.051	0.047	-9999	-0.51	1	1
SHC1	0.008	0.032	-9999	-0.51	2	2
SP1	0.01	0.045	-9999	-0.33	9	9
IL2RA	-0.004	0.11	-9999	-0.39	36	36
IL2RB	0.008	0.032	-9999	-0.5	2	2
SOS1	0.01	0	-9999	-10000	0	0
IL2RG	0.005	0.05	-9999	-0.5	5	5
G1/S transition of mitotic cell cycle	-0.012	0.12	-9999	-0.68	10	10
PTPN11	0.01	0	-9999	-10000	0	0
CCND2	0.011	0.098	-9999	-0.73	9	9
LCK	0.007	0.039	-9999	-0.5	3	3
GRB2	0.01	0	-9999	-10000	0	0
IL2	0.006	0.005	-9999	-10000	0	0
CDK6	0.008	0.032	-9999	-0.5	2	2
CCND3	0.054	0.043	-9999	-0.43	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.003	0.06	-9999	-0.51	7	7
CDC42/GTP	-0.026	0.068	-9999	-0.4	4	4
PLCG1	0	0.082	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.026	0.067	-9999	-0.39	4	4
S1PR5	-0.024	0.13	-9999	-0.5	34	34
S1PR4	-0.017	0.11	-9999	-0.5	27	27
MAPK3	0	0.082	-9999	-0.41	4	4
MAPK1	0	0.082	-9999	-0.41	4	4
S1P/S1P5/Gi	-0.01	0.092	-9999	-0.26	36	36
GNAI1	0.008	0.032	-9999	-0.5	2	2
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.02	0.074	-9999	-0.3	34	34
RHOA	0.011	0.059	-9999	-10000	0	0
S1P/S1P4/Gi	-0.007	0.087	-9999	-0.44	4	4
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.031	0.14	-9999	-0.5	41	41
S1P/S1P4/G12/G13	-0.014	0.059	-9999	-0.26	27	27
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.007	-10000	0	-10000	0	0
HSPA8	0.008	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.012	0.075	0.19	1	-0.32	24	25
AKT1	0.007	0.02	-10000	0	-10000	0	0
GSC	-0.023	0.098	-10000	0	-0.42	1	1
NKX2-5	-0.029	0.13	-10000	0	-0.5	34	34
muscle cell differentiation	0.021	0.053	0.32	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.044	0.056	-10000	0	-10000	0	0
SMAD4	0.018	0.024	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.009	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.011	0.075	-10000	0	-0.29	33	33
SMAD3/SMAD4/VDR	0.009	0.031	-10000	0	-0.32	1	1
MYC	0.011	0.038	-10000	0	-0.5	2	2
CDKN2B	-0.065	0.34	-10000	0	-1.3	38	38
AP1	0.03	0.076	-10000	0	-0.51	3	3
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.044	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.01	0.095	-10000	0	-0.39	8	8
SP3	0.012	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.06	0.18	-10000	0	-0.51	69	69
SMAD3/SMAD4/GR	0.002	0.023	-10000	0	-10000	0	0
GATA3	0.008	0.043	-10000	0	-0.5	3	3
SKI/SIN3/HDAC complex/NCoR1	0.031	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.045	0.1	-10000	0	-0.47	8	8
endothelial cell migration	-0.005	0.067	1.3	1	-10000	0	1
MAX	0.008	0.003	-10000	0	-10000	0	0
RBBP7	0.009	0.001	-10000	0	-10000	0	0
RBBP4	0.009	0.001	-10000	0	-10000	0	0
RUNX2	0.003	0.06	-10000	0	-0.51	7	7
RUNX3	0.007	0.039	-10000	0	-0.5	3	3
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.008	0.003	-10000	0	-10000	0	0
VDR	0.008	0.032	-10000	0	-0.5	2	2
CDKN1A	0.05	0.067	-10000	0	-1.2	1	1
KAT2B	0.011	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.044	0.1	-10000	0	-0.34	22	22
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.009	0.001	-10000	0	-10000	0	0
SERPINE1	0.005	0.067	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.002	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.011	0.066	-10000	0	-0.31	21	21
SAP30	0.009	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.011	0.026	-10000	0	-10000	0	0
JUN	0.031	0.075	-10000	0	-0.51	3	3
SMAD3/SMAD4/IRF7	-0.001	0.04	-10000	0	-0.39	3	3
TFE3	0.015	0.003	-10000	0	-10000	0	0
COL1A2	-0.009	0.088	-10000	0	-0.4	19	19
mesenchymal cell differentiation	0.003	0.042	0.31	7	-10000	0	7
DLX1	-0.024	0.12	-10000	0	-0.51	31	31
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.012	0.11	-10000	0	-0.5	27	27
SMAD3/SMAD4/Max	0.002	0.023	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.005	0.013	-10000	0	-10000	0	0
ZBTB17	0.012	0.015	-10000	0	-10000	0	0
LAMC1	0.044	0.027	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.002	0.022	-10000	0	-10000	0	0
IRF7	0.007	0.043	-10000	0	-0.55	3	3
ESR1	-0.016	0.11	-10000	0	-0.5	25	25
HNF4A	-0.1	0.21	-10000	0	-0.51	112	112
MEF2C	-0.018	0.12	-10000	0	-0.47	6	6
SMAD2-3/SMAD4	-0.006	0.028	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.018	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.006	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.005	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.009	0.001	-10000	0	-10000	0	0
HDAC2	0.009	0.001	-10000	0	-10000	0	0
SNIP1	0.008	0.003	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.004	0.024	-10000	0	-10000	0	0
MSG1/HSC70	-0.023	0.087	-10000	0	-0.36	33	33
SMAD2	0.007	0.022	-10000	0	-10000	0	0
SMAD3	0.019	0.023	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.036	0.025	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.016	0.012	-10000	0	-10000	0	0
NCOR1	0.009	0.001	-10000	0	-10000	0	0
NCOA2	0.005	0.05	-10000	0	-0.5	5	5
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.027	-10000	0	-0.36	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.05	0.054	-10000	0	-10000	0	0
IFNB1	0.031	0.054	-10000	0	-0.52	3	3
SMAD3/SMAD4/MEF2C	-0.005	0.12	-10000	0	-0.48	5	5
CITED1	-0.024	0.12	-10000	0	-0.5	33	33
SMAD2-3/SMAD4/ARC105	-0.004	0.023	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.015	0.14	-10000	0	-0.46	38	38
RUNX1-3/PEBPB2	-0.002	0.022	-10000	0	-0.29	3	3
SMAD7	0.054	0.086	-10000	0	-0.58	3	3
MYC/MIZ-1	0.01	0.045	-10000	0	-0.36	2	2
SMAD3/SMAD4	0.024	0.063	0.28	2	-0.38	1	3
IL10	0.033	0.08	-10000	0	-0.49	10	10
PIASy/HDAC complex	0.008	0.004	-10000	0	-10000	0	0
PIAS3	0.011	0.003	-10000	0	-10000	0	0
CDK2	0.012	0.005	-10000	0	-10000	0	0
IL5	0.033	0.046	-10000	0	-10000	0	0
CDK4	0.007	0.051	-10000	0	-0.51	5	5
PIAS4	0.008	0.004	-10000	0	-10000	0	0
ATF3	-0.012	0.1	-10000	0	-0.5	22	22
SMAD3/SMAD4/SP1	-0.001	0.034	-10000	0	-10000	0	0
FOXG1	-0.055	0.16	-10000	0	-0.51	58	58
FOXO3	0.014	0.026	-10000	0	-10000	0	0
FOXO1	0.014	0.03	-10000	0	-0.35	1	1
FOXO4	0.014	0.026	-10000	0	-10000	0	0
heart looping	-0.018	0.12	-10000	0	-0.47	6	6
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.018	0.08	-10000	0	-0.32	31	31
MYOD1	-0.002	0.039	-10000	0	-0.51	3	3
SMAD3/SMAD4/HNF4	-0.066	0.13	-10000	0	-0.31	112	112
SMAD3/SMAD4/GATA3	-0.002	0.045	-10000	0	-0.34	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.003	0.03	-10000	0	-0.32	2	2
SMAD3/SMAD4/SP1-3	0.021	0.041	-10000	0	-10000	0	0
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.013	0.02	-10000	0	-10000	0	0
SIN3B	0.009	0.001	-10000	0	-10000	0	0
SIN3A	0.009	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.04	0.12	-10000	0	-0.39	19	19
ITGB5	0.05	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.035	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.041	0.11	-10000	0	-0.31	72	72
AR	-0.062	0.18	-10000	0	-0.5	72	72
negative regulation of cell growth	0.036	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.002	0.033	-10000	0	-0.32	3	3
E2F5	0.006	0.045	-10000	0	-0.51	4	4
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.032	0.082	-10000	0	-0.32	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	0.022	0.097	-10000	0	-0.32	37	37
TFDP1	0.009	0.023	-10000	0	-0.51	1	1
SMAD3/SMAD4/AP1	0.034	0.077	-10000	0	-0.51	3	3
SMAD3/SMAD4/RUNX2	-0.003	0.043	-10000	0	-0.31	7	7
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.009	0.022	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.001	0.08	0.52	2	-10000	0	2
IL27/IL27R/JAK1	-0.028	0.085	-10000	0	-1.1	1	1
TBX21	0	0.14	-10000	0	-0.49	23	23
IL12B	0.003	0.056	-10000	0	-0.51	6	6
IL12A	0.004	0.04	-10000	0	-0.36	6	6
IL6ST	-0.011	0.1	-10000	0	-0.5	21	21
IL27RA/JAK1	0.011	0.055	-10000	0	-1.2	1	1
IL27	-0.006	0.084	-10000	0	-0.51	14	14
TYK2	0.01	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.065	0.12	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	-0.001	0.08	0.52	2	-10000	0	2
T cell proliferation during immune response	-0.001	0.08	0.52	2	-10000	0	2
MAPKKK cascade	0.001	0.08	-10000	0	-0.52	2	2
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.002	-10000	0	-10000	0	0
IL12RB1	-0.006	0.086	-10000	0	-0.5	15	15
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.008	0.16	-10000	0	-0.44	43	43
IL27/IL27R/JAK2/TYK2	0	0.08	-10000	0	-0.53	2	2
positive regulation of T cell mediated cytotoxicity	0.001	0.08	-10000	0	-0.52	2	2
STAT1 (dimer)	-0.047	0.12	0.48	1	-0.65	8	9
JAK2	0.008	0.032	-10000	0	-0.5	2	2
JAK1	0.01	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.005	0.076	-10000	0	-0.5	2	2
T cell proliferation	-0.053	0.14	-10000	0	-0.45	20	20
IL12/IL12R/TYK2/JAK2	0.009	0.078	-10000	0	-0.6	2	2
IL17A	-0.065	0.12	-10000	0	-0.57	1	1
mast cell activation	-0.001	0.08	0.52	2	-10000	0	2
IFNG	0	0.027	-10000	0	-0.12	10	10
T cell differentiation	-0.003	0.005	-10000	0	-0.02	24	24
STAT3 (dimer)	0.005	0.076	-10000	0	-0.5	2	2
STAT5A (dimer)	0.005	0.08	-10000	0	-0.62	2	2
STAT4 (dimer)	0.005	0.076	-10000	0	-0.5	2	2
STAT4	0.01	0	-10000	0	-10000	0	0
T cell activation	-0.006	0.006	0.12	1	-10000	0	1
IL27R/JAK2/TYK2	-0.017	0.073	-10000	0	-1.1	1	1
GATA3	0.004	0.08	-10000	0	-1.2	2	2
IL18	0.002	0.051	-10000	0	-0.36	10	10
positive regulation of mast cell cytokine production	0.005	0.075	-10000	0	-0.49	2	2
IL27/EBI3	-0.005	0.064	-10000	0	-0.36	16	16
IL27RA	0.001	0.056	-10000	0	-1.2	1	1
IL6	-0.11	0.22	-10000	0	-0.5	120	120
STAT5A	0.009	0.022	-10000	0	-0.5	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.021	0.46	1	-10000	0	1
IL1B	-0.013	0.088	-10000	0	-0.36	31	31
EBI3	0.007	0.032	-10000	0	-0.51	2	2
TNF	-0.005	0.07	-10000	0	-0.36	19	19

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.014	0.059	-10000	0	-0.5	1	1
ER alpha/Gai/GDP/Gbeta gamma	0.006	0.088	-10000	0	-0.38	13	13
AKT1	0.009	0.11	-10000	0	-0.72	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.006	0.12	-10000	0	-0.73	12	12
mol:Ca2+	0.014	0.087	-10000	0	-0.41	15	15
IGF1R	0.009	0.022	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/Striatin	-0.015	0.066	-10000	0	-0.3	26	26
SHC1	0.008	0.032	-10000	0	-0.51	2	2
apoptosis	-0.009	0.11	0.69	12	-10000	0	12
RhoA/GTP	-0.011	0.047	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.024	0.073	-10000	0	-0.38	14	14
regulation of stress fiber formation	-0.03	0.049	0.36	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.016	0.067	-10000	0	-0.3	27	27
KRAS	0.008	0.032	-10000	0	-0.51	2	2
G13/GTP	-0.013	0.059	-10000	0	-0.27	25	25
pseudopodium formation	0.03	0.049	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1	-0.015	0.065	-10000	0	-0.3	25	25
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.008	0.032	-10000	0	-0.5	2	2
GNAO1	0.003	0.06	-10000	0	-0.51	7	7
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.014	0.088	-10000	0	-0.43	14	14
E2/ER beta (dimer)	-0.001	0.023	-10000	0	-0.36	2	2
mol:GDP	-0.013	0.059	-10000	0	-0.34	13	13
mol:NADP	0.014	0.088	-10000	0	-0.43	14	14
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
mol:IP3	0.014	0.091	-10000	0	-0.43	15	15
IGF-1R heterotetramer	0.009	0.022	-10000	0	-0.5	1	1
PLCB1	0.013	0.081	-10000	0	-0.42	14	14
PLCB2	0.009	0.092	-10000	0	-0.45	15	15
IGF1	-0.002	0.077	-10000	0	-0.5	12	12
mol:L-citrulline	0.014	0.088	-10000	0	-0.43	14	14
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.02	0.072	-10000	0	-0.66	3	3
JNK cascade	-0.001	0.023	-10000	0	-0.36	2	2
BCAR1	0.009	0.022	-10000	0	-0.5	1	1
ESR2	0.008	0.032	-10000	0	-0.5	2	2
GNAQ	0.009	0.022	-10000	0	-0.5	1	1
ESR1	-0.015	0.11	-10000	0	-0.5	25	25
Gq family/GDP/Gbeta gamma	0.023	0.054	-10000	0	-0.43	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.046	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.024	0.072	-10000	0	-0.39	13	13
GNAZ	-0.031	0.14	-10000	0	-0.5	41	41
E2/ER alpha (dimer)	-0.018	0.078	-10000	0	-0.36	25	25
STRN	0.009	0.022	-10000	0	-0.5	1	1
GNAL	-0.002	0.077	-10000	0	-0.5	12	12
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.012	0.031	-10000	0	-0.3	5	5
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.008	0.032	-10000	0	-0.5	2	2
HBEGF	-0.032	0.11	-10000	0	-0.45	11	11
cAMP biosynthetic process	-0.018	0.066	-10000	0	-0.25	37	37
SRC	0.012	0.084	-10000	0	-0.36	13	13
PI3K	-0.001	0.016	-10000	0	-0.35	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.012	0.055	-10000	0	-0.32	12	12
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.023	0.069	-10000	0	-0.34	16	16
Gs family/GTP	-0.018	0.067	-10000	0	-0.25	37	37
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.017	-10000	0	-0.27	2	2
vasodilation	0.014	0.085	-10000	0	-0.41	14	14
mol:DAG	0.014	0.091	-10000	0	-0.43	15	15
Gs family/GDP/Gbeta gamma	-0.016	0.061	-10000	0	-0.34	12	12
MSN	0.03	0.052	-10000	0	-0.39	1	1
Gq family/GTP	-0.017	0.078	-10000	0	-0.45	14	14
mol:PI-3-4-5-P3	0.006	0.11	-10000	0	-0.7	12	12
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.014	0.085	0.41	14	-10000	0	14
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.012	0.055	-10000	0	-0.33	12	12
NOS3	0.013	0.092	-10000	0	-0.45	14	14
GNA11	0.008	0.032	-10000	0	-0.5	2	2
MAPKKK cascade	0.021	0.094	-10000	0	-0.53	12	12
E2/ER alpha (dimer)/PELP1/Src	-0.025	0.076	-10000	0	-0.41	13	13
ruffle organization	0.03	0.049	-10000	0	-0.36	1	1
ROCK2	0.026	0.051	-10000	0	-10000	0	0
GNA14	-0.004	0.083	-10000	0	-0.5	14	14
GNA15	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.036	0.13	-10000	0	-0.44	14	14
MMP2	0.017	0.081	-10000	0	-0.51	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.022	-9999	-0.5	1	1
SPHK1	0.005	0.051	-9999	-0.51	5	5
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.016	0.02	-9999	-0.27	1	1
GNAO1	0.003	0.06	-9999	-0.51	7	7
mol:Sphinganine-1-P	0.013	0.04	-9999	-0.36	6	6
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.009	0.023	-9999	-0.51	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.015	-9999	-0.23	1	1
S1PR5	-0.024	0.13	-9999	-0.5	34	34
S1PR4	-0.017	0.11	-9999	-0.5	27	27
GNAI1	0.008	0.032	-9999	-0.5	2	2
S1P/S1P5/G12	-0.018	0.064	-9999	-0.25	34	34
S1P/S1P3/Gq	0.021	0.055	-9999	-0.27	14	14
S1P/S1P4/Gi	-0.001	0.088	-9999	-0.42	5	5
GNAQ	0.009	0.022	-9999	-0.5	1	1
GNAZ	-0.031	0.14	-9999	-0.5	41	41
GNA14	-0.004	0.083	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.032	-9999	-0.5	2	2
ABCC1	0.01	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.023	0	-9999	-10000	0	0
SNTA1	0.006	0.045	-9999	-0.51	4	4
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.022	0.024	-9999	-0.3	3	3
MAPK12	0.014	0.052	-9999	-0.26	18	18
CCND1	0.007	0.056	-9999	-0.43	7	7
p38 gamma/SNTA1	0.016	0.054	-9999	-0.24	19	19
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.014	0.052	-9999	-0.26	18	18
MAP2K6	0.008	0.057	-9999	-0.29	18	18
MAPT	0.007	0.071	-9999	-0.29	25	25
MAPK13	0.018	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.013	0.014	-9999	-0.31	1	1

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.063	0.17	-9999	-0.71	8	8
RAD9A	0.01	0	-9999	-10000	0	0
AP1	-0.011	0.087	-9999	-0.36	30	30
IFNAR2	0.008	0.005	-9999	-10000	0	0
AKT1	0.002	0.043	-9999	-0.22	7	7
ER alpha/Oestrogen	-0.018	0.079	-9999	-0.37	25	25
NFX1/SIN3/HDAC complex	0.027	0.018	-9999	-10000	0	0
EGF	-0.092	0.2	-9999	-0.51	99	99
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.085	0.14	-9999	-0.69	7	7
SAP18	0.007	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.037	0.14	-9999	-0.51	44	44
WRN	0.01	0	-9999	-10000	0	0
SP1	0.009	0.006	-9999	-10000	0	0
SP3	0.007	0.005	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.079	0.12	-9999	-0.62	7	7
Mad/Max	0.01	0.008	-9999	-10000	0	0
TERT	-0.065	0.18	-9999	-0.73	8	8
CCND1	-0.059	0.2	-9999	-1.2	7	7
MAX	0.007	0.005	-9999	-10000	0	0
RBBP7	0.007	0.004	-9999	-10000	0	0
RBBP4	0.007	0.004	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.007	0.004	-9999	-10000	0	0
Telomerase/911	0.021	0.029	-9999	-10000	0	0
CDKN1B	-0.003	0.084	-9999	-10000	0	0
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.007	0.004	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.007	0.005	-9999	-10000	0	0
JUN	0.005	0.039	-9999	-0.5	3	3
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.019	0.11	-9999	-0.5	27	27
IFN-gamma/IRF1	-0.028	0.095	-9999	-0.35	41	41
PARP2	0.01	0	-9999	-10000	0	0
BLM	-0.041	0.15	-9999	-0.51	50	50
Telomerase	-0.022	0.057	-9999	-10000	0	0
IRF1	0.01	0.007	-9999	-10000	0	0
ESR1	-0.017	0.11	-9999	-0.5	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.02	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.03	0.02	-9999	-10000	0	0
HDAC1	0.007	0.004	-9999	-10000	0	0
HDAC2	0.008	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.02	0.004	-9999	-10000	0	0
ABL1	0.01	0	-9999	-10000	0	0
MXD1	0.007	0.005	-9999	-10000	0	0
MRE11A	0.01	0	-9999	-10000	0	0
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.081	0.13	-9999	-0.68	6	6
NR2F2	0.013	0.007	-9999	-10000	0	0
MAPK3	0.011	0.008	-9999	-10000	0	0
MAPK1	0.011	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.01	0.002	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.01	0	-9999	-10000	0	0
EGFR	-0.009	0.089	-9999	-0.51	16	16
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.081	0.16	-9999	-0.37	111	111
MYC	0.006	0.032	-9999	-0.5	2	2
IL2	0.003	0.01	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
TGFB1	0.01	0.002	-9999	-10000	0	0
TRF2/BLM	-0.032	0.098	-9999	-0.33	50	50
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.082	0.14	-9999	-0.69	7	7
SP1/HDAC2	0.013	0.011	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.079	0.12	-9999	-0.62	7	7
Smad3/Myc	0.021	0.02	-9999	-0.29	2	2
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.031	0.14	-9999	-0.5	41	41
Telomerase/PinX1	-0.079	0.12	-9999	-0.62	7	7
Telomerase/AKT1/mTOR/p70S6K	0.006	0.053	-9999	-10000	0	0
SIN3B	0.007	0.004	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.079	0.12	-9999	-0.62	7	7
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.079	0.12	-9999	-0.62	7	7
E2F1	0	0.065	-9999	-0.52	8	8
ZNFX1	0.007	0.004	-9999	-10000	0	0
PIF1	-0.068	0.18	-9999	-0.51	77	77
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.023	0.094	-9999	-0.34	27	27
MAP3K8	0.008	0.032	-9999	-0.5	2	2
FOS	0.023	0.067	-9999	-0.37	5	5
PRKCA	0.008	0.032	-9999	-0.5	2	2
PTPN7	0.011	0.003	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.004	0.083	-9999	-0.5	14	14
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.017	-9999	-0.28	2	2
MAPK3	0.02	0.039	-9999	-0.21	4	4
MAP2K1	0.018	0.081	-9999	-0.41	16	16
ELK1	0.009	0.005	-9999	-10000	0	0
BRAF	-0.014	0.069	-9999	-0.39	16	16
mol:GTP	0	0.001	-9999	-0.005	27	27
MAPK1	0.02	0.039	-9999	-10000	0	0
RAF1	-0.014	0.069	-9999	-0.39	16	16
KRAS	0.008	0.032	-9999	-0.51	2	2

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.013	0.072	-9999	-0.34	19	19
MAP4K1	0.005	0.05	-9999	-0.5	5	5
MAP3K8	0.008	0.032	-9999	-0.5	2	2
PRKCB	-0.004	0.083	-9999	-0.5	14	14
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
MAP3K1	0.025	0.068	-9999	-0.6	4	4
JUN	0.011	0.11	-9999	-0.62	14	14
MAP3K7	0.025	0.068	-9999	-0.6	4	4
GRAP2	-0.006	0.088	-9999	-0.5	16	16
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.031	0.074	-9999	-0.67	4	4
LAT	0.009	0.023	-9999	-0.51	1	1
LCP2	0.007	0.039	-9999	-0.5	3	3
MAPK8	0.007	0.11	-9999	-0.64	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.019	0.072	-9999	-0.64	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.012	0.067	-9999	-0.61	4	4

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.009	0.022	-10000	0	-0.5	1	1
ANTXR2	0.009	0.022	-10000	0	-0.5	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.066	2	2
monocyte activation	-0.004	0.09	-10000	0	-0.44	19	19
MAP2K2	0	0.002	-10000	0	-10000	0	0
MAP2K1	0	0.003	-10000	0	-10000	0	0
MAP2K7	0	0.003	-10000	0	-10000	0	0
MAP2K6	-0.009	0.047	-10000	0	-0.26	17	17
CYAA	0.011	0.016	-10000	0	-0.25	2	2
MAP2K4	0	0.003	-10000	0	-10000	0	0
IL1B	-0.003	0.066	-10000	0	-0.26	32	32
Channel	-0.001	0.017	-10000	0	-0.27	2	2
NLRP1	-0.001	0.016	-10000	0	-0.26	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.066	2	-10000	0	2
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
PGR	-0.046	0.099	-10000	0	-0.26	91	91
PA/Cellular Receptors	-0.001	0.019	-10000	0	-0.3	2	2
apoptosis	0	0.004	-10000	0	-0.066	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.011	0.017	-10000	0	-0.26	2	2
macrophage activation	0.015	0.004	-10000	0	-10000	0	0
TNF	-0.009	0.096	-10000	0	-0.5	19	19
VCAM1	-0.004	0.09	-10000	0	-0.44	19	19
platelet activation	0	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.013	-10000	0	-10000	0	0
IL18	0.007	0.046	-10000	0	-0.31	10	10
negative regulation of macrophage activation	0	0.004	-10000	0	-0.066	2	2
LEF	0	0.004	-10000	0	-0.066	2	2
CASP1	-0.002	0.017	-10000	0	-0.23	2	2
mol:cAMP	0	0.005	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.066	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.016	-10000	0	-0.25	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.001	-10000	0	-10000	0	0
HDAC2	0.01	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.003	0.032	-10000	0	-0.3	6	6
forebrain development	-0.018	0.15	-10000	0	-0.52	23	23
GNAO1	0.002	0.06	-10000	0	-0.5	7	7
SMO/beta Arrestin2	0.012	0.034	-10000	0	-0.36	4	4
SMO	0.005	0.046	-10000	0	-0.51	4	4
ARRB2	0.009	0.004	-10000	0	-10000	0	0
GLI3/SPOP	0.034	0.036	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
GSK3B	0.01	0	-10000	0	-10000	0	0
GNAI2	0.009	0.004	-10000	0	-10000	0	0
SIN3/HDAC complex	0.006	0.013	-10000	0	-10000	0	0
GNAI1	0.007	0.032	-10000	0	-0.5	2	2
XPO1	0.01	0.005	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.048	0.11	-10000	0	-0.53	15	15
SAP30	0.01	0.001	-10000	0	-10000	0	0
mol:GDP	0.005	0.046	-10000	0	-0.51	4	4
MIM/GLI2A	0.002	0.04	-10000	0	-0.53	1	1
IFT88	0.01	0	-10000	0	-10000	0	0
GNAI3	0.009	0.004	-10000	0	-10000	0	0
GLI2	0.035	0.012	-10000	0	-10000	0	0
GLI3	0.03	0.038	0.18	1	-0.24	7	8
CSNK1D	0.01	0	-10000	0	-10000	0	0
CSNK1E	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.001	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.01	0	-10000	0	-10000	0	0
GNG2	0.008	0.032	-10000	0	-0.5	2	2
Gi family/GTP	0.001	0.078	-10000	0	-0.28	19	19
SIN3B	0.01	0.001	-10000	0	-10000	0	0
SIN3A	0.01	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	0.037	0.033	-10000	0	-10000	0	0
GLI2/Su(fu)	0.04	0.026	-10000	0	-10000	0	0
FOXA2	-0.18	0.39	-10000	0	-1	87	87
neural tube patterning	-0.018	0.15	-10000	0	-0.52	23	23
SPOP	0.01	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.021	0.017	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
CSNK1G2	0.01	0	-10000	0	-10000	0	0
CSNK1G3	0.01	0	-10000	0	-10000	0	0
MTSS1	0.002	0.04	-10000	0	-0.53	1	1
embryonic limb morphogenesis	-0.018	0.15	-10000	0	-0.52	23	23
SUFU	0.019	0.018	-10000	0	-10000	0	0
LGALS3	0.01	0	-10000	0	-10000	0	0
catabolic process	0.053	0.035	-10000	0	-0.3	1	1
GLI3A/CBP	0.004	0.059	-10000	0	-0.33	15	15
KIF3A	0.01	0	-10000	0	-10000	0	0
GLI1	-0.019	0.15	-10000	0	-0.54	23	23
RAB23	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0	-10000	0	-10000	0	0
IFT172	0.01	0	-10000	0	-10000	0	0
RBBP7	0.01	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.021	0.017	-10000	0	-10000	0	0
GNAZ	-0.032	0.14	-10000	0	-0.5	41	41
RBBP4	0.01	0.001	-10000	0	-10000	0	0
CSNK1G1	0.01	0	-10000	0	-10000	0	0
PIAS1	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GLI2/SPOP	0.038	0.011	-10000	0	-10000	0	0
STK36	0.01	0.005	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.008	0.072	-10000	0	-0.5	2	2
PTCH1	-0.02	0.19	-10000	0	-0.92	15	15
MIM/GLI1	-0.049	0.22	-10000	0	-0.49	94	94
CREBBP	0.004	0.059	-10000	0	-0.33	15	15
Su(fu)/SIN3/HDAC complex	0.04	0.007	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

Figure S92. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S92. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.008	0.032	-10000	0	-0.5	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.031	0.02	-10000	0	-10000	0	0
KAT2B	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
AKT1	0.015	0.026	0.2	1	-0.23	2	3
RAR alpha/9cRA/Cyclin H	-0.007	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.029	0.021	-10000	0	-10000	0	0
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.007	0.03	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.001	0.023	-10000	0	-0.36	2	2
RXRs/RARs/NRIP1/9cRA	-0.012	0.068	-10000	0	-0.55	2	2
NCOA2	0.005	0.05	-10000	0	-0.5	5	5
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.008	0.032	-10000	0	-0.5	2	2
RARG	0.01	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
MAPK1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.044	0.058	-10000	0	-0.5	3	3
RARA	0.009	0.041	-10000	0	-0.23	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.027	0.03	-10000	0	-0.22	1	1
PRKCA	0.01	0.032	-10000	0	-0.5	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.026	0.076	-10000	0	-0.59	2	2
RXRG	-0.17	0.18	-10000	0	-0.33	267	267
RXRA	0.016	0.039	-10000	0	-0.22	2	2
RXRB	0.001	0.063	-10000	0	-0.31	2	2
VDR/Vit D3/DNA	-0.001	0.023	-10000	0	-0.36	2	2
RBP1	0.005	0.051	-10000	0	-0.51	5	5
CRBP1/9-cic-RA	-0.004	0.036	-10000	0	-0.37	5	5
RARB	0.01	0.032	-10000	0	-0.5	2	2
PRKCG	-0.043	0.16	-10000	0	-0.5	53	53
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.014	0.067	-10000	0	-0.59	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.005	0.06	-10000	0	-0.45	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.03	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.026	0.076	-10000	0	-0.59	2	2
positive regulation of DNA binding	-0.007	0.023	-10000	0	-0.24	1	1
NRIP1	-0.024	0.072	-10000	0	-0.54	2	2
RXRs/RARs	-0.034	0.078	-10000	0	-0.49	3	3
RXRs/RXRs/DNA/9cRA	-0.048	0.06	-10000	0	-0.61	2	2
PRKACA	0.01	0	-10000	0	-10000	0	0
CDK7	0.01	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.016	-10000	0	-10000	0	0
CCNH	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.005	0.05	-10000	0	-0.5	5	5
CLTC	0.011	0.045	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.003	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.025	0.078	-10000	0	-0.27	47	47
EXOC4	0.01	0	-10000	0	-10000	0	0
CD59	0.013	0.03	-10000	0	-10000	0	0
CPE	0.003	0.06	-10000	0	-0.3	19	19
CTNNB1	0.01	0	-10000	0	-10000	0	0
membrane fusion	0	0	-10000	0	-10000	0	0
CTNND1	0	0.078	-10000	0	-10000	0	0
DNM2	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.019	0.021	-10000	0	-10000	0	0
TSHR	-0.019	0.098	-10000	0	-0.3	54	54
INS	0.007	0.008	-10000	0	-10000	0	0
BIN1	0.01	0	-10000	0	-10000	0	0
mol:Choline	0	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.014	0.092	-10000	0	-0.3	47	47
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.077	-10000	0	-0.27	47	47
JUP	0.013	0.03	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.012	-10000	0	-0.26	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.013	0.032	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.008	0.032	-10000	0	-0.51	2	2
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.01	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.034	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.01	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.017	0.053	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.015	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.001	0.019	-10000	0	-0.3	2	2
ACAP1	0.02	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.025	0.086	-10000	0	-0.34	10	10
clathrin heavy chain/ACAP1	0.016	0.042	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.01	0	-10000	0	-10000	0	0
exocyst	0.034	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0	0.078	-10000	0	-0.25	47	47
NME1	-0.015	0.092	-10000	0	-0.3	47	47
clathrin coat assembly	0.011	0.045	-10000	0	-10000	0	0
IL2RA	0.004	0.045	-10000	0	-10000	0	0
VAMP3	0.015	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.012	0.041	-10000	0	-0.34	3	3
EXOC6	0.01	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.01	0	-10000	0	-10000	0	0
PIP5K1C	0.019	0.021	-10000	0	-10000	0	0
SDC1	0.013	0.03	-10000	0	-10000	0	0
ARF6/GDP	-0.015	0.091	-10000	0	-0.3	47	47
EXOC7	0.01	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.018	0.055	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
endocytosis	0.001	0.012	0.26	1	-10000	0	1
SCAMP2	0.01	0	-10000	0	-10000	0	0
ADRB2	-0.081	0.14	-10000	0	-0.36	31	31
EXOC3	0.01	0	-10000	0	-10000	0	0
ASAP2	0.009	0.022	-10000	0	-0.5	1	1
Dynamin 2/GDP	-0.007	0.083	-10000	0	-0.27	47	47
KLC1	0.01	0	-10000	0	-10000	0	0
AVPR2	-0.04	0.12	-10000	0	-0.36	17	17
RALA	0.01	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.049	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.013	0.052	-9999	-10000	0	0
TC10/GTP	-0.012	0.049	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.012	-9999	-0.27	1	1
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.009	0.022	-9999	-0.5	1	1
GRB14	-0.025	0.13	-9999	-0.51	35	35
FOXO3	-0.003	0.025	-9999	-0.52	1	1
AKT1	0.023	0.061	-9999	-10000	0	0
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0	-9999	-10000	0	0
SORBS1	-0.019	0.12	-9999	-0.5	29	29
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	-0.15	0.13	-9999	-0.25	326	326
CBL/APS/CAP/Crk-II/C3G	-0.014	0.055	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.012	-9999	-0.27	1	1
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.014	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.029	0.013	-9999	-10000	0	0
RPS6KB1	0.029	0.057	-9999	-10000	0	0
PARD6A	0.009	0.022	-9999	-0.5	1	1
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.012	0.044	-9999	-10000	0	0
HRAS/GTP	-0.002	0.021	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.001	0.019	-9999	-10000	0	0
PRKCI	-0.004	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.055	-9999	-10000	0	0
SHC1	0.008	0.032	-9999	-0.51	2	2
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.001	0.014	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	0.023	0.061	-9999	-10000	0	0
PRKCZ	-0.006	0.036	-9999	-0.45	3	3
SH2B2	0.009	0.022	-9999	-0.5	1	1
SHC/SHIP	0.023	0.028	-9999	-10000	0	0
F2RL2	-0.029	0.14	-9999	-0.51	39	39
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.018	-9999	-0.28	2	2
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.016	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.015	0.06	-9999	-10000	0	0
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.017	-9999	-0.28	2	2
INPP5D	0.019	0.024	-9999	-0.25	4	4
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.003	0.035	-9999	-0.79	1	1
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.009	0.022	-9999	-0.5	1	1
p62DOK/RasGAP	0	0.002	-9999	-10000	0	0
INS	0.002	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.024	-9999	-0.25	4	4
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	0.021	0.073	-9999	-0.41	3	3
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.025	0.014	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.001	0.012	-9999	-0.28	1	1
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.019	0.066	-9999	-0.25	40	40

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.025	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.022	0.051	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0.026	0.048	-9999	-10000	0	0
HIF1A	0.016	0	-9999	-10000	0	0
GAB1	0.008	0.032	-9999	-0.5	2	2
AKT1	0.038	0.042	-9999	-10000	0	0
PLCG1	0.022	0.052	-9999	-10000	0	0
NOS3	0.039	0.049	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.039	0.048	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.007	0.093	-9999	-0.51	17	17
VEGFR1 homodimer/NRP2/VEGFR121	-0.001	0.019	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
eNOS/Hsp90	0.043	0.047	-9999	-10000	0	0
endothelial cell proliferation	0.029	0.058	-9999	-0.37	3	3
mol:Ca2+	0.022	0.051	-9999	-10000	0	0
MAPK3	0.031	0.05	-9999	-0.46	1	1
MAPK1	0.031	0.05	-9999	-0.46	1	1
PIK3R1	0.009	0.022	-9999	-0.5	1	1
PLGF homodimer	-0.007	0.092	-9999	-0.51	17	17
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.31	0.25	-9999	-0.5	326	326
VEGFA homodimer	0.01	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.025	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.036	0.049	-9999	-0.44	1	1
PI3K	-0.008	0.043	-9999	-10000	0	0
PRKCA	0.026	0.053	-9999	-0.49	1	1
PRKCB	0.02	0.068	-9999	-0.49	2	2
VEGFR1 homodimer/PLGF homodimer	0.015	0.057	-9999	-10000	0	0
VEGFA	0.01	0	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.022	0.051	-9999	-10000	0	0
RASA1	0.031	0	-9999	-10000	0	0
NRP2	0.007	0.039	-9999	-0.5	3	3
VEGFR1 homodimer	0.024	0	-9999	-10000	0	0
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.11	0.12	-9999	-0.4	13	13
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.043	-9999	-10000	0	0
mol:L-citrulline	0.039	0.048	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0.01	0	-9999	-10000	0	0
PI3K/GAB1	-0.008	0.042	-9999	-10000	0	0
PDPK1	0.031	0.047	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.039	0.048	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.023	0.024	-9999	-10000	0	0

×

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	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.01	0	-10000	0	-10000	0	0
MAP2K3	0.021	0.025	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.029	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.003	0.059	-10000	0	-0.5	7	7
TXN	0.006	0.015	-10000	0	-0.19	3	3
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.008	0.032	-10000	0	-0.5	2	2
GADD45B	0.006	0.045	-10000	0	-0.5	4	4
MAP3K1	0.01	0	-10000	0	-10000	0	0
MAP3K6	0.01	0	-10000	0	-10000	0	0
MAP3K7	0.01	0	-10000	0	-10000	0	0
MAP3K4	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0	0	-10000	0	-10000	0	0
TAK1/TAB family	0.001	0.013	0.17	3	-10000	0	3
RAC1/OSM/MEKK3	-0.001	0.012	-10000	0	-0.26	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.08	0.2	-10000	0	-0.51	89	89
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.053	0.12	-10000	0	-0.3	89	89
MAPK11	0.007	0.039	-10000	0	-0.5	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.047	0.1	-10000	0	-0.27	89	89
OSM/MEKK3	-0.001	0.016	-10000	0	-0.35	1	1
TAOK1	0.013	0.014	-10000	0	-0.31	1	1
TAOK2	0.013	0	-10000	0	-10000	0	0
TAOK3	0.013	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
MAP3K10	0.007	0.039	-10000	0	-0.5	3	3
MAP3K3	0.009	0.022	-10000	0	-0.5	1	1
TRX/ASK1	0.011	0.013	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.006	0.044	-10000	0	-0.29	11	11

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.001	0.016	-9999	-10000	0	0
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.014	-9999	-0.22	2	2
GATA1/HDAC4	-0.037	0.11	-9999	-0.35	54	54
GATA1/HDAC5	-0.036	0.11	-9999	-0.35	53	53
GATA2/HDAC5	-0.028	0.095	-9999	-0.35	41	41
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.002	0.077	-9999	-0.5	12	12
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.013	-9999	-0.3	1	1
HDAC4/ANKRA2	-0.001	0.016	-9999	-0.36	1	1
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.031	0.14	-9999	-0.5	41	41
HDAC4/RFXANK	-0.001	0.016	-9999	-0.36	1	1
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.009	0.022	-9999	-0.5	1	1
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.022	-9999	-0.35	2	2
Histones	0.027	0.03	-9999	-10000	0	0
ADRBK1	0.01	0	-9999	-10000	0	0
HDAC4	0.009	0.023	-9999	-0.51	1	1
XPO1	0.01	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	-0.001	0.016	-9999	-0.36	1	1
HDAC7	0.01	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
HDAC6	0.009	0.023	-9999	-0.51	1	1
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0.001	0.067	-9999	-0.5	9	9
Tubulin/HDAC6	-0.009	0.052	-9999	-0.3	16	16
SUMO1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
GATA1	-0.044	0.15	-9999	-0.5	53	53
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
NR3C1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	-0.001	0.016	-9999	-0.36	1	1
Tubulin	-0.01	0.06	-9999	-0.36	15	15
HDAC4/14-3-3 E	-0.001	0.016	-9999	-0.36	1	1
GNB1	0.01	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.013	-9999	-0.3	1	1
HDAC4/SRF	-0.006	0.04	-9999	-0.29	10	10
HDAC4/ER alpha	-0.018	0.078	-9999	-0.36	26	26
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.03	-9999	-10000	0	0
cell motility	-0.009	0.051	-9999	-0.3	16	16
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.01	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.009	0.023	-9999	-0.51	1	1
Hsp90/HDAC6	-0.001	0.016	-9999	-0.36	1	1
ESR1	-0.015	0.11	-9999	-0.5	25	25
HDAC6/HDAC11	-0.001	0.016	-9999	-0.36	1	1
Ran/GTP/Exportin 1	0	0.01	-9999	-0.22	1	1
NPC	0	0	-9999	-10000	0	0
MEF2C	0.01	0	-9999	-10000	0	0
RAN	0.009	0.023	-9999	-0.51	1	1
HDAC4/MEF2C	0	0.011	-9999	-10000	0	0
GNG2	0.008	0.032	-9999	-0.5	2	2
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	-0.005	0.087	-9999	-0.51	15	15
HDAC11	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
ANKRA2	0.01	0	-9999	-10000	0	0
RFXANK	0.01	0	-9999	-10000	0	0
nuclear import	0	0.008	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.035	0.041	-10000	0	-0.4	1	1
NFATC2	0.012	0.045	-10000	0	-0.2	6	6
NFATC3	0.013	0.03	-10000	0	-0.37	3	3
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.015	0.095	-10000	0	-0.36	18	18
Exportin 1/Ran/NUP214	-0.001	0.013	-10000	0	-0.3	1	1
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.034	0.08	-10000	0	-0.39	15	15
BCL2/BAX	-0.002	0.027	-10000	0	-0.36	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.005	0.007	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.008	0.004	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.015	0.089	-10000	0	-0.34	18	18
Calcineurin A alpha-beta B1/BCL2	0.007	0.039	-10000	0	-0.5	3	3
FKBP8	0.009	0.022	-10000	0	-0.5	1	1
activation-induced cell death of T cells	0.014	0.088	0.34	18	-10000	0	18
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.002	0.064	-10000	0	-0.51	8	8
XPO1	0.009	0.001	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.51	10	10
MAP3K8	0.006	0.032	-10000	0	-0.5	2	2
NFAT4/CK1 alpha	-0.001	0.016	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.053	0.1	-10000	0	-0.38	6	6
CABIN1	-0.016	0.096	-10000	0	-0.37	18	18
CALM1	0.008	0.004	-10000	0	-10000	0	0
RAN	0.008	0.023	-10000	0	-0.51	1	1
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0.001	0.067	-10000	0	-0.5	9	9
mol:Ca2+	-0.003	0.007	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.027	-10000	0	-0.35	3	3
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	0.008	0.004	-10000	0	-10000	0	0
MAPK9	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.004	0.036	-10000	0	-0.34	3	3
PRKCH	0.01	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.004	-10000	0	-10000	0	0
PIM1	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.013	0.21	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.016	-10000	0	-10000	0	0
PRKCB	-0.004	0.083	-10000	0	-0.5	14	14
PRKCE	0.004	0.055	-10000	0	-0.5	6	6
JNK2/NFAT4	0.016	0.028	-10000	0	-0.33	3	3
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.009	0.001	-10000	0	-10000	0	0
PRKCZ	0.005	0.039	-10000	0	-0.5	3	3
PRKCA	0.008	0.032	-10000	0	-0.5	2	2
PRKCG	-0.045	0.16	-10000	0	-0.51	53	53
PRKCQ	-0.063	0.18	-10000	0	-0.5	74	74
FKBP38/BCL2	-0.003	0.031	-10000	0	-0.36	4	4
EP300	0.008	0.005	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.042	-10000	0	-0.38	1	1
CaM/Ca2+/FKBP38	-0.001	0.014	-10000	0	-0.31	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.005	0.039	-10000	0	-0.3	9	9
NFATc/ERK1	0.039	0.039	-10000	0	-0.37	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.034	0.08	-10000	0	-0.39	15	15
NR4A1	-0.056	0.21	-10000	0	-0.48	104	104
GSK3B	0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	0.013	0.03	-10000	0	-0.37	3	3
NFAT1/CK1 alpha	-0.011	0.026	-10000	0	-0.26	1	1
RCH1/ KPNB1	-0.006	0.044	-10000	0	-0.36	8	8
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.008	0.004	-10000	0	-10000	0	0
AKAP5	0.007	0.039	-10000	0	-0.5	3	3
MEF2D	0.008	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.034	0.042	-10000	0	-0.38	1	1
CREBBP	0.008	0.005	-10000	0	-10000	0	0
BCL2	0.007	0.039	-10000	0	-0.5	3	3

×

FoxO family signaling

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
G6PC	0.016	0.046	-9999	-10000	0	0
PLK1	-0.12	0.24	-9999	-0.58	46	46
CDKN1B	0.015	0.11	-9999	-10000	0	0
FOXO3	-0.069	0.2	-9999	-0.5	43	43
KAT2B	0.004	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.014	0.03	-9999	-10000	0	0
CAT	-0.065	0.22	-9999	-1.2	7	7
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.005	0.02	-9999	-10000	0	0
FOXO1	0.021	0.03	-9999	-0.25	1	1
MAPK10	-0.004	0.087	-9999	-0.25	56	56
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.052	0.063	-9999	-10000	0	0
response to oxidative stress	-0.007	0.023	-9999	-10000	0	0
FOXO3A/SIRT1	-0.11	0.15	-9999	-0.47	40	40
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.01	0.004	-9999	-10000	0	0
BCL2L11	0.009	0.031	-9999	-10000	0	0
FOXO1/SKP2	0.021	0.037	-9999	-0.27	3	3
mol:GDP	-0.007	0.023	-9999	-10000	0	0
RAN	0.01	0.023	-9999	-0.51	1	1
GADD45A	0.009	0.11	-9999	-0.71	2	2
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.055	0.016	-9999	-10000	0	0
MST1	-0.018	0.11	-9999	-0.52	22	22
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.02	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.025	0.01	-9999	-10000	0	0
MAPK9	0.025	0.009	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
SIRT1	0.007	0.008	-9999	-10000	0	0
SOD2	0.013	0.13	-9999	-10000	0	0
RBL2	-0.02	0.14	-9999	-0.49	4	4
RAL/GDP	0.013	0.014	-9999	-10000	0	0
CHUK	0.004	0.019	-9999	-10000	0	0
Ran/GTP	0.01	0.017	-9999	-0.36	1	1
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.019	0.015	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.006	0.14	-9999	-1.3	6	6
SKP2	0.006	0.045	-9999	-0.51	4	4
USP7	0.011	0.001	-9999	-10000	0	0
IKBKB	0.004	0.019	-9999	-10000	0	0
CCNB1	-0.094	0.24	-9999	-0.58	41	41
FOXO1-3a-4/beta catenin	-0.033	0.07	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.037	-9999	-0.27	3	3
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.003	0.03	-9999	-0.52	1	1
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.018	0.014	-9999	-0.3	1	1
ZFAND5	0.055	0.056	-9999	-10000	0	0
SFN	0	0.071	-9999	-0.51	10	10
CDK2	0.01	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.022	0.045	-9999	-0.37	1	1
CREBBP	0.01	0.005	-9999	-10000	0	0
FBXO32	-0.075	0.22	-9999	-0.57	41	41
BCL6	-0.02	0.14	-9999	-0.49	4	4
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.023	0.015	-9999	-0.22	2	2
epithelial cell differentiation	-0.001	0.015	-9999	-10000	0	0
CYFIP2	0.003	0.059	-9999	-0.5	7	7
ENAH	0.048	0.031	-9999	-10000	0	0
EGFR	-0.006	0.089	-9999	-0.5	16	16
EPHA2	0	0.07	-9999	-0.5	10	10
MYO6	0.029	0.016	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.034	-9999	-0.29	7	7
AQP5	-0.1	0.17	-9999	-0.42	114	114
CTNND1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.029	0.016	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.13	-9999	-0.46	1	1
EGF	-0.09	0.2	-9999	-0.51	99	99
NCKAP1	0.01	0	-9999	-10000	0	0
AQP3	-0.018	0.087	-9999	-0.44	21	21
cortical microtubule organization	-0.001	0.015	-9999	-10000	0	0
GO:0000145	0.028	0.015	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.001	0.015	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GDP	-0.005	0.031	-9999	-0.39	1	1
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.006	0.037	-9999	-0.26	11	11
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.037	0.02	-9999	-10000	0	0
PVRL2	0.01	0	-9999	-10000	0	0
ZYX	0.028	0.019	-9999	-10000	0	0
ARF6/GTP	-0.005	0.034	-9999	-10000	0	0
CDH1	0.008	0.032	-9999	-0.5	2	2
EGFR/EGFR/EGF/EGF	-0.05	0.096	-9999	-0.46	4	4
RhoA/GDP	-0.001	0.014	-9999	-10000	0	0
actin cytoskeleton organization	0.034	0.015	-9999	-10000	0	0
IGF-1R heterotetramer	0.009	0.022	-9999	-0.5	1	1
GIT1	0.01	0	-9999	-10000	0	0
IGF1R	0.009	0.022	-9999	-0.5	1	1
IGF1	-0.002	0.077	-9999	-0.5	12	12
DIAPH1	-0.008	0.065	-9999	-0.56	7	7
Wnt receptor signaling pathway	0.001	0.015	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.031	-9999	-0.39	1	1
CTNNA1	0.01	0	-9999	-10000	0	0
VCL	0.034	0.016	-9999	-10000	0	0
EFNA1	0.009	0.022	-9999	-0.5	1	1
LPP	0.034	0.019	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.005	0.037	-9999	-0.45	1	1
SEC6/SEC8	-0.001	0.012	-9999	-10000	0	0
MGAT3	-0.11	0.13	-9999	-0.47	1	1
HGF/MET	-0.028	0.078	-9999	-0.46	4	4
HGF	-0.021	0.12	-9999	-0.5	31	31
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.016	-9999	-0.23	2	2
actin cable formation	0.059	0.03	-9999	-10000	0	0
KIAA1543	0.033	0.026	-9999	-0.45	1	1
KIFC3	0.028	0.019	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
EXOC3	0.01	0	-9999	-10000	0	0
ACTN1	0.029	0.016	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.001	0.015	-9999	-10000	0	0
EXOC4	0.01	0	-9999	-10000	0	0
STX4	0.029	0.016	-9999	-10000	0	0
PIP5K1C	0.029	0.016	-9999	-10000	0	0
LIMA1	0.01	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
ROCK1	-0.004	0.027	-9999	-0.34	1	1
adherens junction assembly	0.045	0.037	-9999	-0.52	2	2
IGF-1R heterotetramer/IGF1	-0.006	0.036	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.024	0.13	-9999	-0.5	34	34
PLEKHA7	0.029	0.016	-9999	-10000	0	0
mol:GTP	-0.005	0.037	-9999	-0.26	11	11
establishment of epithelial cell apical/basal polarity	0.048	0.014	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.023	0.015	-9999	-0.22	2	2
regulation of cell-cell adhesion	0.034	0.015	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.016	-9999	-0.23	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.003	0.023	-9999	-10000	0	0
DAPP1	-0.005	0.11	-9999	-0.48	19	19
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.005	0.16	-9999	-0.59	26	26
mol:DAG	0.021	0.069	-9999	-0.3	9	9
HRAS	0.01	0.001	-9999	-10000	0	0
RAP1A	0.01	0.001	-9999	-10000	0	0
ARF5/GDP	0.02	0.072	-9999	-0.4	11	11
PLCG2	0.007	0.039	-9999	-0.5	3	3
PLCG1	0.01	0	-9999	-10000	0	0
ARF5	0.01	0	-9999	-10000	0	0
mol:GTP	-0.002	0.022	-9999	-10000	0	0
ARF1/GTP	-0.003	0.022	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.022	-9999	-10000	0	0
ADAP1	-0.003	0.026	-9999	-0.43	1	1
ARAP3	-0.002	0.022	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PREX1	0.004	0.055	-9999	-0.5	6	6
ARHGEF6	-0.009	0.096	-9999	-0.5	19	19
ARHGEF7	0.01	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
NRAS	0.01	0.001	-9999	-10000	0	0
FYN	0.009	0.022	-9999	-0.5	1	1
ARF6	0.01	0	-9999	-10000	0	0
FGR	-0.029	0.14	-9999	-0.5	39	39
mol:Ca2+	0.019	0.037	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0	0.07	-9999	-0.5	10	10
ZAP70	0.004	0.055	-9999	-0.5	6	6
mol:IP3	0.022	0.05	-9999	-0.21	6	6
LYN	0.01	0	-9999	-10000	0	0
ARF1/GDP	0.02	0.072	-9999	-0.4	11	11
RhoA/GDP	-0.007	0.037	-9999	-0.36	2	2
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.008	0.032	-9999	-0.5	2	2
actin cytoskeleton reorganization	0.038	0.064	-9999	-0.46	4	4
SRC	0.01	0	-9999	-10000	0	0
PLEKHA2	0.021	0.028	-9999	-0.29	4	4
RAC1	0.01	0	-9999	-10000	0	0
PTEN	0	0.003	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.019	-9999	-10000	0	0
RhoA/GTP	-0.002	0.02	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.003	0.12	-9999	-0.48	19	19
BLK	-0.08	0.2	-9999	-0.51	89	89
PDPK1	0.01	0	-9999	-10000	0	0
CYTH1	-0.002	0.02	-9999	-10000	0	0
HCK	-0.014	0.11	-9999	-0.5	24	24
CYTH3	-0.003	0.024	-9999	-10000	0	0
CYTH2	-0.002	0.02	-9999	-10000	0	0
KRAS	0.008	0.032	-9999	-0.5	2	2
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.002	0.027	-9999	-0.57	1	1
SGK1	-0.002	0.029	-9999	-0.62	1	1
INPP5D	0.007	0.039	-9999	-0.5	3	3
mol:GDP	0.015	0.076	-9999	-0.42	11	11
SOS1	0.01	0	-9999	-10000	0	0
SYK	0.007	0.039	-9999	-0.5	3	3
ARF6/GDP	-0.007	0.037	-9999	-0.37	2	2
mol:PI-3-4-5-P3	-0.002	0.022	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.022	-9999	-10000	0	0
VAV1	0.005	0.05	-9999	-0.5	5	5
mol:PI-3-4-P2	0.016	0.028	-9999	-0.35	3	3
RAS family/GTP/PI3K Class I	-0.002	0.022	-9999	-10000	0	0
PLEKHA1	0.022	0.024	-9999	-0.29	3	3
Rac1/GDP	0.02	0.072	-9999	-0.4	11	11
LAT	0.009	0.023	-9999	-0.51	1	1
Rac1/GTP	0.011	0.11	-9999	-0.45	22	22
ITK	-0.008	0.039	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.021	0.093	-9999	-0.35	20	20
LCK	0.007	0.039	-9999	-0.5	3	3
BTK	-0.017	0.063	-9999	-0.43	3	3

×

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	0.008	0.066	-9999	-0.25	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.013	0.044	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.004	0.021	-9999	-0.3	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.014	0.045	-9999	-0.33	4	4
CaM/Ca2+	-0.016	0.053	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.017	0.063	-9999	-10000	0	0
AKT1	0.026	0.059	-9999	-10000	0	0
MAP2K1	0.024	0.062	-9999	-10000	0	0
MAP3K11	0.017	0.064	-9999	-10000	0	0
IFNGR1	0.009	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.054	0.11	-9999	-0.38	50	50
Rap1/GTP	-0.012	0.038	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.019	0.063	-9999	-10000	0	0
CEBPB	0.043	0.086	-9999	-0.41	11	11
STAT3	0.01	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.017	0.056	-9999	-10000	0	0
STAT1	0.017	0.063	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.03	0.14	-9999	-0.5	41	41
PIK3CA	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.022	0.061	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.011	0.041	-9999	-0.35	2	2
mol:Ca2+	-0.017	0.057	-9999	-0.25	1	1
MAPK3	0.033	0.061	-9999	-0.34	1	1
STAT1 (dimer)	-0.017	0.061	-9999	-0.47	4	4
MAPK1	0.033	0.061	-9999	-10000	0	0
JAK2	0.007	0.032	-9999	-0.5	2	2
PIK3R1	0.009	0.022	-9999	-0.5	1	1
JAK1	0.009	0.007	-9999	-10000	0	0
CAMK2D	0.01	0	-9999	-10000	0	0
DAPK1	0.038	0.1	-9999	-0.6	11	11
SMAD7	0.027	0.041	-9999	-0.26	1	1
CBL/CRKL/C3G	-0.014	0.047	-9999	-10000	0	0
PI3K	-0.015	0.051	-9999	-10000	0	0
IFNG	-0.03	0.14	-9999	-0.5	41	41
apoptosis	0.027	0.077	-9999	-0.43	11	11
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.041	0.15	-9999	-0.5	51	51
CAMK2B	-0.08	0.2	-9999	-0.51	89	89
FRAP1	0.026	0.056	-9999	-10000	0	0
PRKCD	0.027	0.06	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
negative regulation of cell growth	-0.014	0.045	-9999	-0.33	4	4
PTPN2	0.01	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
IRF1	0.046	0.051	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.015	0.05	-9999	-10000	0	0
SOCS1	0.001	0.02	-9999	-10000	0	0
mol:GDP	-0.014	0.045	-9999	-10000	0	0
CASP1	0.026	0.05	-9999	-0.3	6	6
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.04	0.03	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.05	-9999	-10000	0	0
RAP1/GDP	-0.012	0.039	-9999	-10000	0	0
CBL	0.016	0.063	-9999	-10000	0	0
MAP3K1	0.017	0.064	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PIAS4	0.009	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.014	0.045	-9999	-0.33	4	4
PTPN11	0.01	0.066	-9999	-0.25	1	1
CREBBP	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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
SPHK2	0.011	0.049	-10000	0	-0.35	9	9
MAP4K4	0.029	0.042	-10000	0	-10000	0	0
BAG4	0.009	0.023	-10000	0	-0.51	1	1
PKC zeta/ceramide	-0.012	0.032	-10000	0	-0.25	2	2
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.003	0.06	-10000	0	-0.51	7	7
BAX	-0.003	0.015	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.007	-10000	0	-10000	0	0
BAD	-0.01	0.03	0.14	4	-10000	0	4
SMPD1	0.017	0.035	-10000	0	-10000	0	0
RB1	-0.01	0.03	0.14	4	-10000	0	4
FADD/Caspase 8	0.036	0.045	-10000	0	-0.45	1	1
MAP2K4	-0.004	0.028	-10000	0	-10000	0	0
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.004	0.028	-10000	0	-10000	0	0
EGF	-0.09	0.2	-10000	0	-0.51	99	99
mol:ceramide	-0.018	0.032	0.14	4	-10000	0	4
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.011	0.049	-10000	0	-0.35	9	9
ASAH1	0.009	0.022	-10000	0	-0.5	1	1
negative regulation of cell cycle	-0.01	0.03	0.14	4	-10000	0	4
cell proliferation	-0.01	0.03	-10000	0	-10000	0	0
BID	0.019	0.033	-10000	0	-10000	0	0
MAP3K1	-0.01	0.03	0.14	4	-10000	0	4
EIF2A	0.002	0.027	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.008	0.032	-10000	0	-0.5	2	2
MAPK3	0.005	0.027	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.005	0.027	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.011	0.029	-10000	0	-10000	0	0
FADD	0.029	0.042	-10000	0	-10000	0	0
KSR1	-0.01	0.03	0.14	4	-10000	0	4
MAPK8	-0.001	0.03	-10000	0	-0.2	2	2
PRKRA	-0.01	0.03	0.14	4	-10000	0	4
PDGFA	0.002	0.063	-10000	0	-0.5	8	8
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	-0.002	0.077	-10000	0	-0.5	12	12
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.018	0.032	0.14	4	-10000	0	4
CTSD	0.01	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.008	0.039	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.011	0.049	-10000	0	-0.35	9	9
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.045	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.011	0.056	-10000	0	-0.29	20	20
mol:Sphingosine-1-phosphate	0.011	0.048	-10000	0	-0.35	9	9
MAP2K1	0.002	0.027	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.005	0.022	0.15	1	-10000	0	1
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.016	-10000	0	-0.36	1	1
EIF2AK2	-0.004	0.028	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.011	0.055	-10000	0	-0.29	19	19
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.038	-10000	0	-0.58	1	1
MAP2K2	0.002	0.027	-10000	0	-10000	0	0
SMPD3	0.016	0.042	-10000	0	-0.29	1	1
TNF	-0.009	0.096	-10000	0	-0.5	19	19
PKC zeta/PAR4	-0.002	0.027	-10000	0	-0.35	3	3
mol:PHOSPHOCHOLINE	0.022	0.065	0.15	96	-10000	0	96
NF kappa B1/RelA/I kappa B alpha	-0.001	0.018	-10000	0	-10000	0	0
AIFM1	-0.005	0.022	0.15	1	-10000	0	1
BCL2	0.007	0.039	-10000	0	-0.5	3	3

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.01	0.053	-9999	-0.29	18	18
Ran/GTP/Exportin 1/HDAC1	0	0.01	-9999	-0.22	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.05	-9999	-0.27	18	18
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.009	0.023	-9999	-0.51	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.009	0.023	-9999	-0.51	1	1
Histones	-0.005	0.024	-9999	-10000	0	0
YY1/LSF	0.024	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.009	0.023	-9999	-0.51	1	1
I kappa B alpha/HDAC3	0.017	0.048	-9999	-0.23	18	18
I kappa B alpha/HDAC1	0.019	0.034	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.021	0.046	-9999	-0.22	18	18
HDAC1/Smad7	-0.001	0.013	-9999	-0.29	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	0.019	0.034	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.012	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.024	0.042	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.031	0.14	-9999	-0.5	41	41
GATA1	-0.044	0.15	-9999	-0.5	53	53
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.024	0.062	-9999	-0.28	1	1
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.015	0.038	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.01	0	-9999	-10000	0	0
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.01	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	0.028	0.032	-9999	-10000	0	0
YY1/HDAC2	0.024	0	-9999	-10000	0	0
YY1/HDAC1	0.024	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.037	0	-9999	-10000	0	0
PPARG	-0.049	0.12	-9999	-0.3	83	83
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.019	0.034	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.013	-9999	-0.29	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.039	0.012	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.015	0.038	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.024	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.009	0.022	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0.01	0	-9999	-10000	0	0
STAT3	0.02	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.038	-9999	-10000	0	0
histone deacetylation	0.037	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.005	0.026	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	-0.004	0.086	-9999	-0.27	41	41
GATA1/HDAC1	-0.036	0.11	-9999	-0.35	53	53
GATA1/HDAC3	-0.013	0.091	-9999	-0.26	53	53
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.067	-9999	-0.35	19	19
SIN3/HDAC complex/Mad/Max	0.037	0	-9999	-10000	0	0
NuRD Complex	0.043	0.012	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.005	0.024	-9999	-10000	0	0
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC1	0.023	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.037	0.11	-9999	-0.36	53	53
FKBP25/HDAC1/HDAC2	-0.001	0.013	-9999	-0.3	1	1
TNF	-0.009	0.096	-9999	-0.5	19	19
negative regulation of cell growth	0.037	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.037	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.22	1	1
NF kappa B/RelA/I kappa B alpha	-0.01	0.054	-9999	-0.29	18	18
SIN3/HDAC complex/NCoR1	0.036	0	-9999	-10000	0	0
TFCP2	0.01	0	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.008	0.032	-9999	-0.5	2	2
MBD2	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.047	0.036	-10000	0	-0.44	1	1
UGCG	-0.002	0.028	-10000	0	-0.62	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.04	0.054	-10000	0	-0.31	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.021	0.03	-10000	0	-0.61	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.037	-10000	0	-0.37	3	3
FRAP1	0.063	0.058	-10000	0	-0.39	5	5
FOXO3	0.065	0.052	-10000	0	-0.35	4	4
AKT1	0.061	0.054	-10000	0	-0.38	4	4
GAB2	0.006	0.05	-10000	0	-0.5	5	5
SMPD1	-0.001	0.007	-10000	0	-10000	0	0
SGMS1	-0.001	0.007	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.014	-10000	0	-0.29	1	1
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.039	0.032	-10000	0	-0.32	1	1
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.019	0.017	-10000	0	-0.35	1	1
RPS6KB1	0.021	0.022	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.001	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	0.012	0.001	-10000	0	-10000	0	0
PIK3R1	0.011	0.022	-10000	0	-0.5	1	1
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.062	0.074	-10000	0	-0.92	2	2
MYB	0.016	0.11	-10000	0	-1.2	4	4
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.054	0.05	-10000	0	-0.35	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.02	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.054	0.049	-10000	0	-0.34	3	3
Rac1/GDP	0.022	0.013	-10000	0	-0.26	1	1
T cell proliferation	0.056	0.051	-10000	0	-0.37	2	2
SHC1	0.008	0.032	-10000	0	-0.51	2	2
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.007	-10000	0	-0.051	7	7
PRKCZ	0.057	0.053	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	-0.004	0.037	-10000	0	-0.4	2	2
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.042	0.039	-10000	0	-0.43	2	2
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	-0.026	0.13	-10000	0	-0.51	36	36
IL2RB	0.01	0.032	-10000	0	-0.5	2	2
TERT	-0.15	0.24	-10000	0	-0.51	157	157
E2F1	0.019	0.043	-10000	0	-0.42	4	4
SOS1	0.01	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.003	0.024	7	-10000	0	7
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.05	-10000	0	-0.5	5	5
actin cytoskeleton organization	0.056	0.051	-10000	0	-0.37	2	2
GRB2	0.01	0.001	-10000	0	-10000	0	0
IL2	0.008	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.027	0.013	-10000	0	-0.24	1	1
LCK	0.009	0.039	-10000	0	-0.5	3	3
BCL2	0.064	0.063	-10000	0	-0.64	2	2

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.006	0.045	-10000	0	-0.5	4	4
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.006	0.089	-10000	0	-0.5	16	16
AKT	0.028	0.034	-10000	0	-0.33	4	4
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.009	0.022	-10000	0	-0.5	1	1
AKT3	0.006	0.045	-10000	0	-0.5	4	4
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.024	0.13	-10000	0	-0.5	34	34
PIK3CA	0.01	0	-10000	0	-10000	0	0
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
PIK3CG	-0.008	0.094	-10000	0	-0.5	18	18
PIK3R3	0.009	0.022	-10000	0	-0.5	1	1
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.01	0	-10000	0	-10000	0	0
RAS	0.007	0.046	-10000	0	-0.25	5	5
ERBB2	0.007	0.039	-10000	0	-0.51	3	3
proliferation/survival/translation	-0.019	0.033	0.2	5	-10000	0	5
PI3K	0.012	0.052	-10000	0	-0.23	10	10
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
KRAS	0.008	0.032	-10000	0	-0.51	2	2
FOXO	0.036	0.014	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.019	0.072	-9999	-0.49	5	5
CLOCK	0.012	0.002	-9999	-10000	0	0
TIMELESS/CRY2	0.03	0.034	-9999	-10000	0	0
DEC1/BMAL1	0	0.001	-9999	-10000	0	0
ATR	0.01	0	-9999	-10000	0	0
NR1D1	0.031	0.02	-9999	-10000	0	0
ARNTL	0.012	0.002	-9999	-10000	0	0
TIMELESS	0.029	0.038	-9999	-10000	0	0
NPAS2	0.009	0.039	-9999	-0.5	3	3
CRY2	0.01	0	-9999	-10000	0	0
mol:CO	-0.01	0.009	-9999	-10000	0	0
CHEK1	-0.026	0.13	-9999	-0.51	36	36
mol:HEME	0.01	0.009	-9999	-10000	0	0
PER1	-0.01	0.098	-9999	-0.5	20	20
BMAL/CLOCK/NPAS2	0.031	0.026	-9999	-0.29	3	3
BMAL1/CLOCK	0.034	0.033	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.019	0.072	-9999	-0.49	5	5
TIMELESS/CHEK1/ATR	-0.02	0.073	-9999	-0.49	5	5
mol:NADPH	0.01	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.019	0.065	-9999	-0.52	1	1
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.002	0.004	-9999	-10000	0	0

×

Arf6 downstream 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.03	0.011	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.004	-10000	0	-10000	0	0
myoblast fusion	-0.015	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.006	0.1	0.29	54	-10000	0	54
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.008	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.002	-10000	0	-10000	0	0
lamellipodium assembly	0.009	0.028	-10000	0	-10000	0	0
MAPK3	0.021	0.007	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.006	0.1	-10000	0	-0.29	54	54
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0.001	0.01	-10000	0	-10000	0	0
ARF1/GDP	0.025	0.016	-10000	0	-10000	0	0
ARF6	0.009	0.002	-10000	0	-10000	0	0
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	0.001	0.07	-10000	0	-0.5	10	10
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.007	-10000	0	-10000	0	0
actin filament bundle formation	0	0.005	-10000	0	-10000	0	0
KALRN	0.005	0.028	-10000	0	-0.26	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0.005	-10000	0	-10000	0	0
NME1	-0.036	0.15	-10000	0	-0.5	47	47
Rac1/GDP	0	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.009	0.028	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0.007	0.024	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.017	0.003	-10000	0	-10000	0	0
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.028	-10000	0	-10000	0	0
ruffle organization	0.023	0.004	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.017	0.003	-10000	0	-10000	0	0
PIP5K1A	0.023	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.028	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.01	0	-10000	0	-10000	0	0
CRKL	0.014	0.044	-10000	0	-0.26	12	12
GRB2/SOS1/SHC	-0.001	0.019	-10000	0	-0.3	2	2
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.014	0.044	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1/PTP1B	-0.007	0.044	-10000	0	-0.28	13	13
AKT1	0.03	0.039	-10000	0	-0.38	1	1
BAD	0.035	0.038	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0.044	-10000	0	-0.26	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.006	0.041	-10000	0	-0.26	12	12
RAF1	0.037	0.037	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.038	-10000	0	-0.44	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.045	-10000	0	-0.29	12	12
PIK3CA	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.03	0.039	-10000	0	-0.38	1	1
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.032	0.033	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.006	0.038	-10000	0	-0.41	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.039	-10000	0	-0.37	2	2
IGF-1R heterotetramer	0.008	0.025	-10000	0	-0.51	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.006	0.041	-10000	0	-0.26	12	12
Crk/p130 Cas/Paxillin	-0.006	0.037	-10000	0	-0.41	1	1
IGF1R	0.008	0.025	-10000	0	-0.51	1	1
IGF1	-0.002	0.079	-10000	0	-0.51	12	12
IRS2/Crk	0.019	0.043	-10000	0	-0.43	1	1
PI3K	-0.006	0.039	-10000	0	-0.43	1	1
apoptosis	-0.037	0.034	0.31	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.024	0.057	-10000	0	-0.35	11	11
RAF1/14-3-3 E	0.04	0.033	-10000	0	-10000	0	0
BAD/14-3-3	0.039	0.035	-10000	0	-0.33	1	1
PRKCZ	0.028	0.043	-10000	0	-0.38	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.005	0.028	-10000	0	-0.32	1	1
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.019	0.06	-10000	0	-0.36	12	12
BCAR1	0.009	0.022	-10000	0	-0.5	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.007	0.043	-10000	0	-0.36	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	0.014	0.043	-10000	0	-0.26	12	12
GRB10	0.01	0	-10000	0	-10000	0	0
PTPN11	0.014	0.044	-10000	0	-0.26	12	12
IRS1	0.008	0.047	-10000	0	-0.28	13	13
IRS2	0.014	0.045	-10000	0	-0.26	13	13
IGF-1R heterotetramer/IGF1	-0.009	0.059	-10000	0	-0.37	13	13
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	0.024	0.041	-10000	0	-0.41	1	1
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	0.012	0.079	-10000	0	-0.37	11	11
SHC1	0.008	0.032	-10000	0	-0.51	2	2

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.009	0.022	-9999	-0.5	1	1
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.003	0.075	-9999	-0.23	43	43
GNAO1	0.004	0.06	-9999	-0.51	7	7
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-0.27	1	1
AKT1	-0.008	0.034	-9999	-0.62	1	1
AKT3	0.021	0.11	-9999	-1.1	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.022	-9999	-0.5	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.009	0.032	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.023	-9999	-0.51	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.013	0.071	-9999	-0.47	2	2
MAPK3	0.018	0.067	-9999	-0.45	2	2
MAPK1	0.018	0.067	-9999	-0.45	2	2
JAK2	0.021	0.068	-9999	-0.4	3	3
CXCR4	0.018	0.067	-9999	-0.45	2	2
FLT1	0.012	0.003	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.018	0.067	-9999	-0.45	2	2
S1P/S1P3/Gi	0.013	0.071	-9999	-0.48	2	2
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.054	-9999	-0.43	2	2
VEGFA	0.012	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	0.011	0.068	-9999	-0.42	2	2
VEGFR1 homodimer/VEGFA homodimer	0.021	0.006	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.016	0.051	-9999	-0.25	16	16
GNAQ	0.009	0.022	-9999	-0.5	1	1
GNAZ	-0.03	0.14	-9999	-0.5	41	41
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.004	0.083	-9999	-0.5	14	14
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.032	-9999	-0.5	2	2
Rac1/GTP	-0.017	0.054	-9999	-0.43	2	2

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.007	0.041	-10000	0	-0.25	14	14
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.028	-10000	0	-0.37	3	3
GNB1/GNG2	-0.001	0.019	-10000	0	-0.3	2	2
GNB1	0.01	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	-0.006	0.042	-10000	0	-0.28	12	12
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	0.002	0.011	0.074	12	-10000	0	12
GNAL	-0.002	0.077	-10000	0	-0.5	12	12
GNG2	0.008	0.032	-10000	0	-0.5	2	2
CRH	0	0.039	-10000	0	-0.51	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.005	0.025	-10000	0	-0.32	3	3

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.004	0.055	-10000	0	-0.5	6	6
positive regulation of NF-kappaB transcription factor activity	-0.005	0.047	-10000	0	-0.4	7	7
MAP2K4	0.034	0.028	-10000	0	-0.33	1	1
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.008	0.032	-10000	0	-0.5	2	2
SMPD1	-0.002	0.02	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.008	0.032	-10000	0	-0.5	2	2
TRAIL/TRAILR2	-0.004	0.038	-10000	0	-0.35	6	6
TRAIL/TRAILR3	-0.009	0.063	-10000	0	-0.4	12	12
TRAIL/TRAILR1	-0.005	0.048	-10000	0	-0.4	7	7
TRAIL/TRAILR4	-0.005	0.048	-10000	0	-0.4	7	7
TRAIL/TRAILR1/DAP3/GTP	-0.004	0.037	-10000	0	-0.3	7	7
IKK complex	-0.001	0.013	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.013	0.04	-10000	0	-0.35	6	6
MAP3K1	-0.003	0.026	-10000	0	-0.36	1	1
TRAILR4 (trimer)	0.008	0.032	-10000	0	-0.5	2	2
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.008	0.032	-10000	0	-0.5	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.025	0.033	-10000	0	-0.46	1	1
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.013	0.04	-10000	0	-0.35	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.004	0.033	-10000	0	-0.49	1	1
mol:ceramide	-0.002	0.02	-10000	0	-10000	0	0
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	0.039	0.027	-10000	0	-0.31	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.002	0.063	-10000	0	-0.5	8	8
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.005	0.04	-10000	0	-0.33	7	7
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.004	0.044	0.24	1	-0.35	6	7
JNK cascade	-0.005	0.047	-10000	0	-0.4	7	7
TRAIL (trimer)	0.004	0.055	-10000	0	-0.5	6	6
TNFRSF10C	0.002	0.063	-10000	0	-0.5	8	8
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.004	0.034	-10000	0	-0.5	1	1
TRAIL/TRAILR2/FADD	-0.003	0.031	-10000	0	-0.29	6	6
cell death	-0.002	0.019	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.026	0.025	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	-0.001	0.039	-10000	0	-0.86	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.025	-10000	0	-10000	0	0

×

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

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
BAG4	0.009	0.023	-9999	-0.51	1	1
Caspase 8 (4 units)	-0.006	0.039	-9999	-0.34	4	4
NEF	0.002	0.018	-9999	-10000	0	0
NFKBIA	0.011	0.011	-9999	-10000	0	0
BIRC3	0.028	0.059	-9999	-0.47	7	7
CYCS	0.035	0.044	-9999	-0.3	4	4
RIPK1	0.01	0	-9999	-10000	0	0
CD247	0.006	0.06	-9999	-0.52	6	6
MAP2K7	0.036	0.037	-9999	-0.33	1	1
protein ubiquitination	0.05	0.033	-9999	-10000	0	0
CRADD	0.008	0.032	-9999	-0.5	2	2
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.004	0.055	-9999	-0.5	6	6
BID	0.031	0.046	-9999	-0.32	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.003	0.028	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
CFLAR	0.01	0	-9999	-10000	0	0
FADD	0.01	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.003	0.028	-9999	-10000	0	0
MAPK8	0.041	0.035	-9999	-10000	0	0
APAF1	0.01	0	-9999	-10000	0	0
TRAF1	0.01	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.025	0.048	-9999	-0.29	10	10
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.043	0.038	-9999	-10000	0	0
CHUK	0.051	0.034	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.003	0.032	-9999	-0.49	1	1
TCRz/NEF	-0.007	0.052	-9999	-0.35	11	11
TNF	-0.009	0.096	-9999	-0.5	19	19
FASLG	0.012	0.076	-9999	-0.55	8	8
NFKB1	0.011	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.011	0.056	-9999	-0.29	20	20
CASP6	-0.004	0.035	-9999	-0.6	1	1
CASP7	0.06	0.056	-9999	-0.48	3	3
RELA	0.011	0.011	-9999	-10000	0	0
CASP2	0.01	0	-9999	-10000	0	0
CASP3	0.06	0.056	-9999	-0.48	3	3
TNFRSF1A	0.01	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.016	-9999	-0.36	1	1
CASP8	0.009	0.022	-9999	-0.5	1	1
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.047	0.037	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.042	-9999	-0.39	2	2
BCL2	0.043	0.04	-9999	-0.37	1	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.031	0.028	-9999	-0.42	2	2
KLHL20	-0.011	0.034	-9999	-0.25	2	2
CYFIP2	0.003	0.059	-9999	-0.5	7	7
Rac1/GDP	0.049	0.02	-9999	-10000	0	0
ENAH	0.031	0.028	-9999	-0.42	2	2
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.01	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.024	-9999	-0.17	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.02	-9999	-10000	0	0
RAPGEF1	0.041	0.025	-9999	-0.35	2	2
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.002	0.027	-9999	-0.43	2	2
CRK	0.036	0.027	-9999	-0.39	2	2
E-cadherin/gamma catenin/alpha catenin	-0.002	0.022	-9999	-0.29	3	3
alphaE/beta7 Integrin	-0.001	0.016	-9999	-0.35	1	1
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.031	0.028	-9999	-0.42	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.009	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.03	0.089	-9999	-0.28	54	54
PI3K	-0.001	0.011	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.002	0.027	-9999	-0.36	3	3
TIAM1	0	0.07	-9999	-0.5	10	10
E-cadherin(dimer)/Ca2+	-0.001	0.015	-9999	-10000	0	0
AKT1	0	0.006	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2
RhoA/GDP	0.049	0.02	-9999	-10000	0	0
actin cytoskeleton organization	-0.008	0.025	-9999	-0.18	2	2
CDC42/GDP	0.049	0.02	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.017	-9999	-0.23	2	2
ITGB7	0.009	0.022	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.001	0.016	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.001	0.015	-9999	-0.25	2	2
mol:GDP	0.048	0.022	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.009	0.023	-9999	-0.51	1	1
p120 catenin/RhoA/GDP	-0.001	0.015	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.018	0.034	-9999	-0.21	7	7
NME1	-0.037	0.15	-9999	-0.51	47	47
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.028	-9999	-0.42	2	2
regulation of cell-cell adhesion	-0.001	0.009	-9999	-10000	0	0
WASF2	-0.004	0.012	-9999	-10000	0	0
Rap1/GTP	-0.001	0.012	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.021	-9999	-10000	0	0
CCND1	0.021	0.042	-9999	-0.26	7	7
VAV2	0.038	0.04	-9999	-0.47	3	3
RAP1/GDP	0	0.013	-9999	-10000	0	0
adherens junction assembly	0.031	0.027	-9999	-0.4	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.002	0.019	-9999	-10000	0	0
E-cadherin/beta catenin	-0.001	0.021	-9999	-0.34	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.031	0.028	-9999	-0.42	2	2
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.017	0.053	-9999	-0.42	2	2
E-cadherin/beta catenin/alpha catenin	-0.001	0.018	-9999	-0.29	2	2
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.028	-9999	-0.44	2	2

×

PDGFR-beta signaling 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
S1P1/Sphingosine-1-phosphate	-0.003	0.034	-9999	-0.55	1	1
PDGFB-D/PDGFRB/SLAP	-0.009	0.059	-9999	-0.38	12	12
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.018	-9999	-0.29	2	2
AKT1	0.044	0.029	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.023	0.042	-9999	-0.59	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.036	0.14	-9999	-0.51	39	39
mol:Ca2+	0.021	0.038	-9999	-0.63	1	1
MYC	0.031	0.07	-9999	-0.68	3	3
SHC1	0.008	0.032	-9999	-0.51	2	2
HRAS/GDP	0.002	0.013	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.006	0.054	-9999	-0.4	8	8
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.021	0.039	-9999	-0.65	1	1
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.004	0.055	-9999	-0.5	6	6
PDGFB-D/PDGFRB/SHP2	0	0.016	-9999	-0.36	1	1
PDGFB-D/PDGFRB/GRB10	0	0.016	-9999	-0.36	1	1
cell cycle arrest	-0.009	0.059	-9999	-0.38	12	12
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.048	0.027	-9999	-10000	0	0
GAB1	0.019	0.049	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.023	0.045	-9999	-0.57	1	1
PDGFB-D/PDGFRB	0.006	0.018	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0.016	-9999	-0.36	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.004	0.034	-9999	-0.51	1	1
positive regulation of MAPKKK cascade	0	0.016	-9999	-0.36	1	1
PIK3R1	0.009	0.022	-9999	-0.5	1	1
mol:IP3	0.021	0.039	-9999	-0.65	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.009	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.004	0.042	-9999	-0.36	7	7
SHB	0.009	0.022	-9999	-0.5	1	1
BLK	-0.015	0.052	-9999	-0.47	5	5
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0.016	-9999	-0.36	1	1
BCAR1	0.009	0.022	-9999	-0.5	1	1
VAV2	0.019	0.066	-9999	-0.55	2	2
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.016	-9999	-0.36	1	1
LCK	0	0.036	-9999	-0.45	3	3
PDGFRB	0.01	0.023	-9999	-0.51	1	1
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.021	0.12	-9999	-0.53	24	24
ABL1	0.017	0.051	-9999	-0.6	1	1
PDGFB-D/PDGFRB/CBL	0.017	0.055	-9999	-0.73	1	1
PTPN1	0.01	0.001	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0	-9999	-10000	0	0
cell proliferation	0.031	0.064	-9999	-0.6	3	3
SLA	-0.002	0.077	-9999	-0.5	12	12
actin cytoskeleton reorganization	0.039	0.02	-9999	-10000	0	0
SRC	0.002	0.017	-9999	-0.34	1	1
PI3K	-0.003	0.026	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.005	0.039	-9999	-0.3	9	9
SH2B2	0.009	0.022	-9999	-0.5	1	1
PLCgamma1/SPHK1	0.024	0.043	-9999	-0.62	1	1
LYN	0.003	0.017	-9999	-0.34	1	1
LRP1	0.006	0.045	-9999	-0.5	4	4
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.009	0.022	-9999	-0.5	1	1
NCK1-2/p130 Cas	0.002	0.017	-9999	-10000	0	0
SPHK1	0.005	0.051	-9999	-0.5	5	5
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.021	0.039	-9999	-0.65	1	1
PLCG1	0.021	0.04	-9999	-0.67	1	1
NHERF/PDGFRB	-0.005	0.036	-9999	-0.29	8	8
YES1	0.003	0.017	-9999	-0.34	1	1
cell migration	-0.005	0.036	-9999	-0.29	8	8
SHC/Grb2/SOS1	0.001	0.02	-9999	-10000	0	0
SLC9A3R2	0.005	0.05	-9999	-0.5	5	5
SLC9A3R1	0.008	0.032	-9999	-0.51	2	2
NHERF1-2/PDGFRB/PTEN	-0.004	0.032	-9999	-0.26	8	8
FYN	0.002	0.028	-9999	-0.43	2	2
DOK1	0.026	0.013	-9999	-0.27	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.004	0.055	-9999	-0.5	6	6
RAC1	0.028	0.066	-9999	-0.53	3	3
PRKCD	0.026	0.013	-9999	-0.27	1	1
FER	0.026	0.013	-9999	-0.27	1	1
MAPKKK cascade	-0.001	0.017	-9999	-10000	0	0
RASA1	0.026	0.013	-9999	-0.27	1	1
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.008	0.017	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.022	-9999	-0.36	2	2
chemotaxis	0.017	0.049	-9999	-0.58	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.013	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0.016	-9999	-0.37	1	1
PTPRJ	0.01	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.012	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.016	-9999	-0.35	1	1
NFKBIA	0.036	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.007	0.036	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
NEMO/ATM	0.039	0.009	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.009	0.023	-9999	-0.51	1	1
Exportin 1/RanGTP	-0.001	0.013	-9999	-0.3	1	1
IKK complex/ELKS	0	0.006	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.009	0.022	-9999	-0.5	1	1
NFKB1	0.012	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
TNF/TNFR1A	-0.013	0.067	-9999	-0.35	19	19
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.032	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.009	0.096	-9999	-0.5	19	19
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0	0.007	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.013	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.022	-9999	-0.5	1	1
ITGA4	0.008	0.032	-9999	-0.5	2	2
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
alpha4/beta1 Integrin	-0.001	0.022	-9999	-0.35	2	2

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.059	0.031	-10000	0	-10000	0	0
CRKL	0.034	0.033	-10000	0	-0.43	1	1
mol:DAG	0.039	0.026	-10000	0	-0.31	1	1
HRAS	0.05	0.038	-10000	0	-0.54	1	1
MAPK8	0.027	0.025	-10000	0	-0.28	1	1
RAP1A	0.034	0.033	-10000	0	-0.43	1	1
GAB1	0.033	0.042	-10000	0	-0.67	1	1
MAPK14	0.027	0.025	-10000	0	-0.28	1	1
EPO	0.005	0.046	-10000	0	-0.51	4	4
PLCG1	0.04	0.026	-10000	0	-0.31	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.003	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.005	0.037	-10000	0	-0.3	8	8
GAB1/SHC/GRB2/SOS1	-0.004	0.034	-10000	0	-0.58	1	1
EPO/EPOR (dimer)	0.014	0.034	-10000	0	-0.36	4	4
IRS2	0.034	0.037	-10000	0	-0.43	2	2
STAT1	0.047	0.029	-10000	0	-0.31	1	1
STAT5B	0.044	0.028	-10000	0	-0.31	1	1
cell proliferation	0.032	0.023	-10000	0	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.005	0.037	-10000	0	-0.46	2	2
TEC	0.034	0.033	-10000	0	-0.43	1	1
SOCS3	0.006	0.045	-10000	0	-0.5	4	4
STAT1 (dimer)	0.047	0.028	-10000	0	-0.3	1	1
JAK2	0.009	0.033	-10000	0	-0.51	2	2
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
EPO/EPOR (dimer)/JAK2	0.039	0.035	-10000	0	-0.46	1	1
EPO/EPOR	0.014	0.034	-10000	0	-0.36	4	4
LYN	0.011	0.001	-10000	0	-10000	0	0
TEC/VAV2	0.04	0.034	-10000	0	-0.41	1	1
elevation of cytosolic calcium ion concentration	0.012	0.003	-10000	0	-10000	0	0
SHC1	0.008	0.032	-10000	0	-0.51	2	2
EPO/EPOR (dimer)/LYN	0.025	0.028	-10000	0	-0.29	4	4
mol:IP3	0.039	0.026	-10000	0	-0.31	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.036	-10000	0	-0.4	3	3
SH2B3	0.009	0.032	-10000	0	-0.5	2	2
NFKB1	0.027	0.025	-10000	0	-0.28	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.034	0.24	2	-0.34	2	4
PTPN6	0.029	0.034	-10000	0	-0.45	1	1
TEC/VAV2/GRB2	0.043	0.033	-10000	0	-0.4	1	1
EPOR	0.012	0.003	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	3	3
mol:GDP	-0.004	0.034	-10000	0	-0.59	1	1
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	0.007	0.039	-10000	0	-0.5	3	3
CRKL/CBL/C3G	0.043	0.031	-10000	0	-0.4	1	1
VAV2	0.034	0.034	-10000	0	-0.43	1	1
CBL	0.034	0.033	-10000	0	-0.43	1	1
SHC/Grb2/SOS1	-0.004	0.028	-10000	0	-0.4	1	1
STAT5A	0.043	0.035	-10000	0	-0.4	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.057	0.039	-10000	0	-0.39	2	2
LYN/PLCgamma2	-0.002	0.027	-10000	0	-0.35	3	3
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	0.017	0.079	-10000	0	-0.43	6	6
BCL2	0.058	0.05	-10000	0	-0.81	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.022	0.026	-9999	-0.34	2	2
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.032	-9999	-0.5	2	2
alpha4/beta7 Integrin/MAdCAM1	-0.005	0.036	-9999	-10000	0	0
EPO	0.002	0.045	-9999	-0.51	4	4
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.022	-9999	-0.35	2	2
EPO/EPOR (dimer)	-0.003	0.032	-9999	-0.36	4	4
lamellipodium assembly	0	0.012	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
JAK2	0.004	0.036	-9999	-0.43	2	2
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
MADCAM1	0.002	0.06	-9999	-0.51	7	7
cell adhesion	-0.005	0.036	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.023	0.03	-9999	-10000	0	0
ITGB7	0.009	0.022	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.003	0.031	-9999	-0.29	6	6
p130Cas/Crk/Dock1	0.037	0.028	-9999	-10000	0	0
VCAM1	0.006	0.045	-9999	-0.5	4	4
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.016	-9999	-10000	0	0
BCAR1	0.028	0.031	-9999	-10000	0	0
EPOR	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0	0.012	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.033	0.041	-10000	0	-10000	0	0
BAG4	0.009	0.023	-10000	0	-0.51	1	1
BAD	0.023	0.017	-10000	0	-10000	0	0
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.003	0.06	-10000	0	-0.51	7	7
BAX	0.023	0.017	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.013	-10000	0	-10000	0	0
IKBKB	0.038	0.04	-10000	0	-10000	0	0
MAP2K2	0.032	0.02	-10000	0	-10000	0	0
MAP2K1	0.032	0.02	-10000	0	-10000	0	0
SMPD1	0.015	0.013	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.042	-10000	0	-10000	0	0
MAP2K4	0.028	0.018	-10000	0	-10000	0	0
protein ubiquitination	0.039	0.04	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.036	0.023	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.029	0.02	-10000	0	-10000	0	0
CRADD	0.008	0.032	-10000	0	-0.5	2	2
mol:ceramide	0.018	0.018	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.024	0.018	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
RELA/p50	0.01	0	-10000	0	-10000	0	0
MAPK3	0.034	0.02	-10000	0	-10000	0	0
MAPK1	0.034	0.02	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.033	0.041	-10000	0	-10000	0	0
KSR1	0.024	0.019	-10000	0	-10000	0	0
MAPK8	0.033	0.017	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.038	0.04	-10000	0	-10000	0	0
TNF R/SODD	-0.001	0.016	-10000	0	-0.36	1	1
TNF	-0.009	0.096	-10000	0	-0.5	19	19
CYCS	0.025	0.018	0.13	1	-10000	0	1
IKBKG	0.038	0.04	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.028	0.043	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AIFM1	0.025	0.018	0.13	1	-10000	0	1
TNF/TNF R/SODD	-0.011	0.056	-10000	0	-0.29	20	20
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.021	0.033	-10000	0	-0.68	1	1
NSMAF	0.033	0.041	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.007	0.039	-10000	0	-0.5	3	3

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.002	0.022	-9999	-0.29	3	3
E-cadherin/beta catenin	-0.001	0.022	-9999	-0.35	2	2
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.009	0.023	-9999	-0.51	1	1
CDH1	0.008	0.032	-9999	-0.5	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.033	0	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.008	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.027	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.001	0.022	-9999	-0.35	2	2
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.008	0.032	-9999	-0.5	2	2
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.002	0.064	-9999	-0.51	8	8
PIAS4	0.01	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.003	0.027	-10000	0	-0.29	3	3
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.032	0.036	0.2	1	-0.32	3	4
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.018	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	0.005	0.023	-10000	0	-0.51	1	1
PRKCI	0.01	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.025	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	3	3
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.034	0.018	-10000	0	-10000	0	0
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.032	0.039	0.21	1	-0.36	3	4
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.02	0	-10000	0	-10000	0	0
SFN	0	0.071	-10000	0	-0.51	10	10
LNPEP	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

mTOR signaling 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.016	-10000	0	-0.25	2	2
FRAP1	0.012	0.005	-10000	0	-10000	0	0
AKT1	-0.001	0.014	-10000	0	-10000	0	0
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.004	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.013	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.015	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.009	-10000	0	-10000	0	0
MAP3K5	0.008	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.022	-10000	0	-0.5	1	1
apoptosis	0.008	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	0.026	0.009	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.006	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.002	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.018	-10000	0	-0.26	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.009	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.013	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	1	1
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.014	-10000	0	-0.24	1	1
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.003	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.006	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.012	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	1	-10000	0	1
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	0.006	0.016	-10000	0	-0.35	1	1
INS	0	0	-10000	0	-10000	0	0
PTEN	0.009	0	-10000	0	-10000	0	0
PDK2	-0.001	0.014	-10000	0	-0.24	1	1
EIF4EBP1	0.007	0.01	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.017	0.005	-10000	0	-10000	0	0
peptide biosynthetic process	0.013	0	-10000	0	-10000	0	0
RHEB	0.009	0.023	-10000	0	-0.51	1	1
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.013	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.013	0.009	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

Figure S125. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S125. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.029	0	-9999	-10000	0	0
CDKN1A	0.029	0.011	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.01	0	-9999	-10000	0	0
FOXO3	0.029	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
AKT3	0.011	0.029	-9999	-0.31	4	4
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.029	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.01	0	-9999	-10000	0	0
RAF1	0.01	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.029	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
AKT1/RAF1	0.029	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.029	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.019	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAPKAP1	0.01	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.033	0.012	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
AKT1S1	0.029	0	-9999	-10000	0	0
CASP9	0.029	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.034	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0.009	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.003	-9999	-10000	0	0
CHUK	0.029	0	-9999	-10000	0	0
BAD/BCL-XL	0.039	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.013	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.045	0.013	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.028	0.016	-9999	-10000	0	0
MAPKKK cascade	-0.028	0	-9999	-10000	0	0
MDM2/Cbp/p300	0.037	0.015	-9999	-10000	0	0
TSC1/TSC2	0.034	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.012	-9999	-10000	0	0
glucose import	0.021	0.027	-9999	-0.26	5	5
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.003	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.021	0.028	-9999	-0.26	5	5
GSK3A	0.029	0	-9999	-10000	0	0
FOXO1	0.029	0.011	-9999	-10000	0	0
GSK3B	0.029	0	-9999	-10000	0	0
SFN	0	0.071	-9999	-0.51	10	10
G1/S transition of mitotic cell cycle	0.034	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.016	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
KPNA1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
RHEB	0.009	0.023	-9999	-0.51	1	1
CREBBP	0.01	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.008	0.032	-9999	-0.5	2	2
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.002	0.027	-9999	-0.35	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.018	-9999	-0.29	2	2
alpha4/beta7 Integrin/Paxillin	-0.002	0.02	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.018	-9999	-0.34	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.009	0.022	-9999	-0.5	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
ARF6/GTP	-0.001	0.013	-9999	-10000	0	0
cell adhesion	-0.001	0.018	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.016	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.009	0.022	-9999	-0.5	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.003	0.025	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.001	0.013	-9999	-0.29	1	1
VCAM1	0.006	0.045	-9999	-0.5	4	4
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.018	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.015	-9999	-10000	0	0
BCAR1	0.009	0.022	-9999	-0.5	1	1
mol:GDP	0.001	0.015	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.018	-9999	-10000	0	0
Rac1/GTP	-0.001	0.02	-9999	-0.38	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.001	0.016	-9999	-0.35	1	1
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.019	-9999	-10000	0	0
NFKBIA	0.021	0.022	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0	-9999	-10000	0	0
ARRB2	0.013	0	-9999	-10000	0	0
REL	0.01	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.014	-9999	-0.29	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.016	0	-9999	-10000	0	0
PIK3R1	0.009	0.022	-9999	-0.5	1	1
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.026	0.022	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.038	0.019	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.016	-9999	-0.35	1	1
NF kappa B1 p50/RelA	0.026	0.022	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.007	0.039	-9999	-0.5	3	3
I kappa B alpha/PIK3R1	0.024	0.024	-9999	-0.23	1	1
cell death	-0.002	0.014	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0	-9999	-10000	0	0
LCK	0.007	0.039	-9999	-0.5	3	3
BCL3	0.009	0.022	-9999	-0.5	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.012	-9999	-10000	0	0
MDM2/SUMO1	0.022	0.016	-9999	-0.24	2	2
HDAC4	0.009	0.023	-9999	-0.51	1	1
Ran/GTP/Exportin 1/HDAC1	0	0.009	-9999	-10000	0	0
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.022	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.009	0.023	-9999	-0.51	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0.012	-9999	-0.24	1	1
SUMO1/HDAC1	0.023	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.016	-9999	-0.26	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	0	0.01	-9999	-0.24	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.008	0.032	-9999	-0.51	2	2
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0.01	-9999	-0.22	1	1
NPC	0	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.038	0.016	-9999	-10000	0	0
adherens junction organization	0.031	0.025	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.035	0.043	-9999	-10000	0	0
FMN1	0.024	0.05	-9999	-10000	0	0
mol:IP3	-0.001	0.012	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.018	-9999	-10000	0	0
CTNNB1	0.009	0.001	-9999	-10000	0	0
AKT1	0.037	0.016	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.027	-9999	-0.36	2	2
CTNND1	0.011	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0.033	0.017	-9999	-10000	0	0
VASP	0.033	0.017	-9999	-10000	0	0
ZYX	0.033	0.02	-9999	-10000	0	0
JUB	0.033	0.023	-9999	-10000	0	0
EGFR(dimer)	0.025	0.048	-9999	-0.32	1	1
E-cadherin/beta catenin-gamma catenin	-0.002	0.022	-9999	-0.28	3	3
mol:PI-3-4-5-P3	-0.001	0.014	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.014	-9999	-10000	0	0
FYN	0.021	0.062	-9999	-10000	0	0
mol:Ca2+	-0.001	0.012	-9999	-10000	0	0
JUP	0.008	0.023	-9999	-0.51	1	1
PIK3R1	0.009	0.022	-9999	-0.5	1	1
mol:DAG	-0.001	0.012	-9999	-10000	0	0
CDH1	0.007	0.032	-9999	-0.5	2	2
RhoA/GDP	0.035	0.043	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.033	0.017	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
EGFR	-0.006	0.089	-9999	-0.5	16	16
CASR	0.011	0.075	-9999	-10000	0	0
RhoA/GTP	-0.001	0.011	-9999	-10000	0	0
AKT2	0.037	0.016	-9999	-10000	0	0
actin cable formation	0.029	0.049	-9999	-10000	0	0
apoptosis	0.001	0.013	-9999	-10000	0	0
CTNNA1	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.031	0.046	-9999	-10000	0	0
PIP5K1A	0.033	0.017	-9999	-10000	0	0
PLCG1	-0.001	0.012	-9999	-10000	0	0
Rac1/GTP	-0.007	0.038	-9999	-0.29	1	1
homophilic cell adhesion	0.001	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	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0	-9999	-10000	0	0
CD4	0	0.07	-9999	-0.5	10	10
CLTA	0.01	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.01	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.021	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.024	0.031	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.006	0.04	-9999	-0.29	10	10

×

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	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.S2.AA1A	TCGA.O1.A52J	TCGA.NJ.A7XG	TCGA.NJ.A55R
109_MAP3K5	0.043	0.043	-0.15	0.043
47_PPARGC1A	0.0097	0.0097	-0.5	0.0097
105_BMP4	0.0097	0.0097	0.0097	0.0097
105_BMP6	0.0097	-0.5	-0.5	0.0097
105_BMP7	-0.51	0.0097	0.0097	0.0097
105_BMP2	0.0097	0.0097	0.0097	0.0097
131_RELN/VLDLR	0	-0.26	-0.26	0
30_TGFB1/TGF beta receptor Type II	0.0093	0.0092	0.0092	0.013
84_STAT5B	0.035	0.035	-0.057	0.037
84_STAT5A	0.035	0.035	-0.057	0.037