PARADIGM pathway analysis of mRNASeq expression and copy number data - Prostate Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	96
Angiopoietin receptor Tie2-mediated signaling	89
Signaling mediated by p38-alpha and p38-beta	87
Glypican 2 network	87
Endothelins	75
Glucocorticoid receptor regulatory network	67
Nephrin/Neph1 signaling in the kidney podocyte	57
IL23-mediated signaling events	57
Reelin signaling pathway	55
Integrins in angiogenesis	49

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
Ephrin A reverse signaling	0.1932	96	677	7	-0.049	0	1000	-1000	-0.011	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1791	89	7910	88	-0.29	0.075	1000	-1000	-0.059	-1000
Signaling mediated by p38-alpha and p38-beta	0.1751	87	3854	44	-0.15	0.027	1000	-1000	-0.015	-1000
Glypican 2 network	0.1751	87	349	4	0.031	0.061	1000	-1000	0.021	-1000
Endothelins	0.1509	75	7295	96	-0.19	0.028	1000	-1000	-0.041	-1000
Glucocorticoid receptor regulatory network	0.1348	67	7713	114	-0.41	0.21	1000	-1000	-0.038	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1147	57	1940	34	-0.05	0.03	1000	-1000	-0.027	-1000
IL23-mediated signaling events	0.1147	57	3435	60	-0.3	0.046	1000	-1000	-0.07	-1000
Reelin signaling pathway	0.1107	55	3126	56	-0.095	0.07	1000	-1000	-0.022	-1000
Integrins in angiogenesis	0.0986	49	4161	84	-0.099	0.083	1000	-1000	-0.024	-1000
Thromboxane A2 receptor signaling	0.0966	48	5126	105	-0.12	0.037	1000	-1000	-0.034	-1000
EPHB forward signaling	0.0946	47	4015	85	-0.075	0.094	1000	-1000	-0.044	-1000
Aurora B signaling	0.0926	46	3112	67	-0.091	0.12	1000	-1000	-0.026	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0905	45	3576	78	-0.12	0.059	1000	-1000	-0.032	-1000
S1P5 pathway	0.0845	42	724	17	-0.045	0.042	1000	-1000	-0.002	-1000
Ras signaling in the CD4+ TCR pathway	0.0845	42	724	17	-0.081	0.041	1000	-1000	-0.011	-1000
HIF-1-alpha transcription factor network	0.0805	40	3049	76	-0.073	0.07	1000	-1000	-0.046	-1000
Ephrin B reverse signaling	0.0805	40	1924	48	-0.068	0.034	1000	-1000	-0.029	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0805	40	2736	68	-0.16	0.062	1000	-1000	-0.074	-1000
LPA receptor mediated events	0.0785	39	4007	102	-0.057	0.1	1000	-1000	-0.058	-1000
Noncanonical Wnt signaling pathway	0.0765	38	1010	26	-0.04	0.027	1000	-1000	-0.028	-1000
S1P1 pathway	0.0744	37	1353	36	-0.19	0.026	1000	-1000	-0.027	-1000
IL6-mediated signaling events	0.0744	37	2848	75	-0.16	0.032	1000	-1000	-0.05	-1000
Signaling events mediated by the Hedgehog family	0.0724	36	1911	52	-0.041	0.037	1000	-1000	-0.022	-1000
p75(NTR)-mediated signaling	0.0724	36	4566	125	-0.073	0.072	1000	-1000	-0.046	-1000
Osteopontin-mediated events	0.0704	35	1364	38	-0.054	0.051	1000	-1000	-0.021	-1000
EPO signaling pathway	0.0704	35	1978	55	-0.019	0.048	1000	-1000	-0.02	-1000
EGFR-dependent Endothelin signaling events	0.0704	35	753	21	-0.029	0.045	1000	-1000	-0.028	-1000
amb2 Integrin signaling	0.0684	34	2831	82	-0.11	0.1	1000	-1000	-0.026	-1000
Nongenotropic Androgen signaling	0.0684	34	1791	52	-0.12	0.06	1000	-1000	-0.021	-1000
S1P4 pathway	0.0684	34	857	25	-0.045	0.048	1000	-1000	-0.017	-1000
Wnt signaling	0.0664	33	235	7	-0.03	0.027	1000	-1000	0	-1000
Syndecan-1-mediated signaling events	0.0644	32	1098	34	-0.019	0.1	1000	-1000	-0.022	-1000
BMP receptor signaling	0.0644	32	2633	81	-0.079	0.067	1000	-1000	-0.013	-1000
Calcium signaling in the CD4+ TCR pathway	0.0644	32	1020	31	-0.088	0.032	1000	-1000	-0.039	-1000
JNK signaling in the CD4+ TCR pathway	0.0624	31	530	17	-0.12	0.065	1000	-1000	-0.023	-1000
Signaling events regulated by Ret tyrosine kinase	0.0624	31	2599	82	-0.03	0.044	1000	-1000	-0.03	-1000
Effects of Botulinum toxin	0.0624	31	819	26	-0.027	0.05	1000	-1000	-0.01	-1000
Glypican 1 network	0.0604	30	1458	48	-0.034	0.063	1000	-1000	-0.024	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0604	30	3703	120	-0.073	0.089	1000	-1000	-0.039	-1000
Fc-epsilon receptor I signaling in mast cells	0.0563	28	2756	97	-0.067	0.04	1000	-1000	-0.037	-1000
PLK1 signaling events	0.0563	28	2397	85	-0.026	0.081	1000	-1000	-0.025	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0563	28	1479	52	-0.046	0.068	1000	-1000	-0.022	-1000
TCR signaling in naïve CD8+ T cells	0.0563	28	2653	93	-0.056	0.073	1000	-1000	-0.035	-1000
Arf6 signaling events	0.0543	27	1720	62	-0.037	0.043	1000	-1000	-0.02	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0543	27	2364	85	-0.12	0.034	1000	-1000	-0.042	-1000
IL4-mediated signaling events	0.0543	27	2475	91	-0.24	0.12	1000	-1000	-0.1	-1000
FOXM1 transcription factor network	0.0543	27	1393	51	-0.095	0.067	1000	-1000	-0.11	-1000
IL12-mediated signaling events	0.0503	25	2188	87	-0.17	0.065	1000	-1000	-0.056	-1000
Plasma membrane estrogen receptor signaling	0.0503	25	2162	86	-0.13	0.055	1000	-1000	-0.031	-1000
Visual signal transduction: Cones	0.0483	24	948	38	-0.041	0.042	1000	-1000	-0.021	-1000
Regulation of p38-alpha and p38-beta	0.0483	24	1317	54	-0.098	0.06	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0483	24	3013	125	-0.06	0.051	1000	-1000	-0.026	-1000
Rapid glucocorticoid signaling	0.0483	24	493	20	-0.054	0.033	1000	-1000	-0.013	-1000
Presenilin action in Notch and Wnt signaling	0.0463	23	1406	61	-0.12	0.073	1000	-1000	-0.032	-1000
PDGFR-alpha signaling pathway	0.0463	23	1020	44	-0.13	0.051	1000	-1000	-0.032	-1000
Canonical Wnt signaling pathway	0.0463	23	1182	51	-0.12	0.12	1000	-1000	-0.039	-1000
ErbB2/ErbB3 signaling events	0.0443	22	1469	65	-0.08	0.037	1000	-1000	-0.047	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0443	22	1211	54	-0.095	0.07	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	0.0443	22	1518	69	-0.008	0.044	1000	-1000	-0.037	-1000
Aurora C signaling	0.0443	22	157	7	0	0.067	1000	-1000	-0.008	-1000
FAS signaling pathway (CD95)	0.0443	22	1048	47	-0.22	0.042	1000	-1000	-0.032	-1000
BARD1 signaling events	0.0423	21	1202	57	-0.03	0.045	1000	-1000	-0.041	-1000
Signaling events mediated by PTP1B	0.0423	21	1621	76	-0.14	0.096	1000	-1000	-0.029	-1000
BCR signaling pathway	0.0423	21	2170	99	-0.11	0.064	1000	-1000	-0.053	-1000
Visual signal transduction: Rods	0.0423	21	1111	52	-0.041	0.058	1000	-1000	-0.012	-1000
IL27-mediated signaling events	0.0402	20	1035	51	-0.35	0.077	1000	-1000	-0.054	-1000
S1P3 pathway	0.0402	20	843	42	-0.028	0.04	1000	-1000	-0.03	-1000
a4b1 and a4b7 Integrin signaling	0.0382	19	95	5	0.015	0.034	1000	-1000	0.017	-1000
IL1-mediated signaling events	0.0382	19	1190	62	-0.037	0.067	1000	-1000	-0.022	-1000
Ceramide signaling pathway	0.0362	18	1394	76	-0.022	0.072	1000	-1000	-0.025	-1000
Syndecan-4-mediated signaling events	0.0362	18	1242	67	-0.049	0.098	1000	-1000	-0.029	-1000
IGF1 pathway	0.0362	18	1069	57	-0.017	0.059	1000	-1000	-0.02	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0362	18	613	33	-0.066	0.061	1000	-1000	-0.021	-1000
HIF-2-alpha transcription factor network	0.0342	17	773	43	-0.048	0.049	1000	-1000	-0.035	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0342	17	1274	74	-0.14	0.052	1000	-1000	-0.047	-1000
Insulin Pathway	0.0342	17	1307	74	-0.12	0.076	1000	-1000	-0.039	-1000
Caspase cascade in apoptosis	0.0322	16	1234	74	-0.038	0.063	1000	-1000	-0.027	-1000
Regulation of nuclear SMAD2/3 signaling	0.0322	16	2204	136	-0.07	0.15	1000	-1000	-0.03	-1000
Coregulation of Androgen receptor activity	0.0322	16	1237	76	-0.015	0.068	1000	-1000	-0.027	-1000
ErbB4 signaling events	0.0322	16	1115	69	-0.08	0.059	1000	-1000	-0.029	-1000
Nectin adhesion pathway	0.0322	16	1050	63	-0.037	0.061	1000	-1000	-0.025	-1000
TCGA08_p53	0.0322	16	118	7	-0.013	0.026	1000	-1000	-0.009	-1000
TCGA08_retinoblastoma	0.0322	16	129	8	-0.01	0.058	1000	-1000	-0.002	-1000
VEGFR1 specific signals	0.0322	16	943	56	-0.055	0.042	1000	-1000	-0.031	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0302	15	432	28	-0.026	0.051	1000	-1000	-0.021	-1000
Cellular roles of Anthrax toxin	0.0302	15	599	39	-0.023	0.026	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0302	15	977	65	-0.22	0.065	1000	-1000	-0.027	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0302	15	589	37	-0.02	0.063	1000	-1000	-0.021	-1000
ceramide signaling pathway	0.0302	15	753	49	0	0.038	1000	-1000	-0.039	-1000
IL2 signaling events mediated by PI3K	0.0302	15	886	58	-0.037	0.07	1000	-1000	-0.027	-1000
Class I PI3K signaling events	0.0302	15	1140	73	-0.042	0.063	1000	-1000	-0.025	-1000
Signaling events mediated by PRL	0.0302	15	530	34	-0.037	0.046	1000	-1000	-0.033	-1000
Regulation of Androgen receptor activity	0.0302	15	1073	70	-0.078	0.042	1000	-1000	-0.031	-1000
Aurora A signaling	0.0282	14	880	60	-0.061	0.074	1000	-1000	-0.019	-1000
FOXA2 and FOXA3 transcription factor networks	0.0282	14	644	46	-0.056	0.044	1000	-1000	-0.086	-1000
TCGA08_rtk_signaling	0.0282	14	387	26	-0.013	0.048	1000	-1000	-0.011	-1000
mTOR signaling pathway	0.0262	13	712	53	-0.14	0.05	1000	-1000	-0.019	-1000
Retinoic acid receptors-mediated signaling	0.0262	13	789	58	-0.042	0.049	1000	-1000	-0.032	-1000
IL2 signaling events mediated by STAT5	0.0262	13	300	22	-0.014	0.048	1000	-1000	-0.017	-1000
LPA4-mediated signaling events	0.0221	11	139	12	-0.03	0.021	1000	-1000	-0.017	-1000
IFN-gamma pathway	0.0221	11	812	68	-0.023	0.073	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class III	0.0221	11	444	40	-0.068	0.05	1000	-1000	-0.039	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0201	10	885	83	-0.047	0.049	1000	-1000	-0.022	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0201	10	466	45	0	0.063	1000	-1000	-0.036	-1000
PDGFR-beta signaling pathway	0.0201	10	1028	97	-0.1	0.07	1000	-1000	-0.042	-1000
Class I PI3K signaling events mediated by Akt	0.0181	9	624	68	-0.033	0.05	1000	-1000	-0.022	-1000
Paxillin-dependent events mediated by a4b1	0.0181	9	333	36	-0.046	0.048	1000	-1000	-0.025	-1000
Syndecan-3-mediated signaling events	0.0181	9	345	35	-0.022	0.072	1000	-1000	-0.014	-1000
FoxO family signaling	0.0161	8	556	64	-0.021	0.06	1000	-1000	-0.048	-1000
E-cadherin signaling in the nascent adherens junction	0.0161	8	663	76	-0.019	0.056	1000	-1000	-0.039	-1000
Regulation of Telomerase	0.0161	8	822	102	-0.025	0.058	1000	-1000	-0.026	-1000
E-cadherin signaling in keratinocytes	0.0161	8	351	43	-0.016	0.046	1000	-1000	-0.017	-1000
Canonical NF-kappaB pathway	0.0141	7	284	39	-0.004	0.056	1000	-1000	-0.021	-1000
Atypical NF-kappaB pathway	0.0141	7	243	31	-0.01	0.031	1000	-1000	-0.022	-1000
p38 MAPK signaling pathway	0.0141	7	349	44	-0.03	0.069	1000	-1000	-0.018	-1000
Signaling mediated by p38-gamma and p38-delta	0.0101	5	83	15	-0.017	0.029	1000	-1000	-0.024	-1000
Class IB PI3K non-lipid kinase events	0.0101	5	15	3	-0.028	0.028	1000	-1000	-0.021	-1000
Signaling events mediated by HDAC Class II	0.0080	4	313	75	-0.028	0.065	1000	-1000	-0.024	-1000
PLK2 and PLK4 events	0.0080	4	13	3	-0.013	0.027	1000	-1000	-0.023	-1000
Circadian rhythm pathway	0.0080	4	101	22	-0.007	0.039	1000	-1000	-0.023	-1000
Insulin-mediated glucose transport	0.0080	4	133	32	-0.013	0.046	1000	-1000	-0.021	-1000
TRAIL signaling pathway	0.0080	4	216	48	-0.011	0.049	1000	-1000	-0.025	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0060	3	85	23	0.008	0.053	1000	-1000	-0.016	-1000
Signaling events mediated by HDAC Class I	0.0040	2	309	104	-0.052	0.064	1000	-1000	-0.035	-1000
Arf6 trafficking events	0.0040	2	210	71	-0.046	0.05	1000	-1000	-0.036	-1000
Arf1 pathway	0.0040	2	119	54	-0.006	0.048	1000	-1000	-0.012	-1000
Arf6 downstream pathway	0.0020	1	67	43	-0.053	0.054	1000	-1000	-0.032	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	11	27	-0.011	0.059	1000	-1000	-0.026	-1000
E-cadherin signaling events	0.0000	0	0	5	0.024	0.046	1000	-1000	0.018	-1000
Alternative NF-kappaB pathway	0.0000	0	9	13	0	0.07	1000	-1000	0	-1000
Total	NA	3178	186867	7203	-9	7.6	131000	-131000	-3.8	-131000

Ephrin A reverse signaling

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.028	0.1	0.13	1	-0.19	136	137
EFNA5	-0.003	0.094	0.17	1	-0.31	42	43
FYN	-0.045	0.074	0.18	3	-0.18	107	110
neuron projection morphogenesis	-0.028	0.1	0.13	1	-0.19	136	137
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.028	0.1	0.13	1	-0.19	136	137
EPHA5	-0.049	0.14	0.17	2	-0.31	111	113

×

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	-0.21	0.39	-10000	0	-0.8	142	142
NCK1/PAK1/Dok-R	-0.11	0.17	-10000	0	-0.39	135	135
NCK1/Dok-R	-0.23	0.44	-10000	0	-0.9	141	141
PIK3CA	0.024	0.027	-10000	0	-0.31	3	3
mol:beta2-estradiol	0.067	0.11	0.24	143	-10000	0	143
RELA	0.026	0.006	-10000	0	-10000	0	0
SHC1	0.025	0.006	-10000	0	-10000	0	0
Rac/GDP	0.018	0.006	-10000	0	-10000	0	0
F2	0.075	0.13	0.26	147	-10000	0	147
TNIP2	0.027	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	-0.21	0.43	-10000	0	-0.86	141	141
FN1	0.02	0.052	0.17	4	-0.31	11	15
PLD2	-0.26	0.45	-10000	0	-0.94	143	143
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
GRB14	0.048	0.062	0.17	82	-0.31	3	85
ELK1	-0.23	0.41	-10000	0	-0.86	142	142
GRB7	0.027	0.004	-10000	0	-10000	0	0
PAK1	0.022	0.037	-10000	0	-0.31	6	6
Tie2/Ang1/alpha5/beta1 Integrin	-0.22	0.46	-10000	0	-0.92	141	141
CDKN1A	-0.14	0.28	-10000	0	-0.58	124	124
ITGA5	0.018	0.054	0.17	1	-0.31	13	14
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.23	0.45	-10000	0	-0.9	142	142
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:NO	-0.14	0.29	0.43	1	-0.6	137	138
PLG	-0.26	0.46	-10000	0	-0.95	143	143
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.19	0.37	-10000	0	-0.76	138	138
GRB2	0.026	0.005	-10000	0	-10000	0	0
PIK3R1	0.021	0.031	-10000	0	-0.31	4	4
ANGPT2	-0.14	0.26	-10000	0	-0.63	79	79
BMX	-0.26	0.46	-10000	0	-0.96	142	142
ANGPT1	-0.29	0.49	-10000	0	-1.1	136	136
tube development	-0.17	0.3	-10000	0	-0.62	139	139
ANGPT4	0.022	0.016	0.18	1	-10000	0	1
response to hypoxia	-0.018	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.25	0.49	-10000	0	-0.97	143	143
alpha5/beta1 Integrin	0.032	0.042	0.14	1	-0.21	13	14
FGF2	0.005	0.081	0.18	1	-0.31	31	32
STAT5A (dimer)	-0.18	0.35	-10000	0	-0.72	131	131
mol:L-citrulline	-0.14	0.29	0.43	1	-0.6	137	138
AGTR1	0.036	0.09	0.18	80	-0.31	20	100
MAPK14	-0.25	0.46	-10000	0	-0.95	143	143
Tie2/SHP2	-0.15	0.34	-10000	0	-0.94	70	70
TEK	-0.16	0.38	-10000	0	-1	70	70
RPS6KB1	-0.2	0.37	0.4	1	-0.77	141	142
Angiotensin II/AT1	0.028	0.062	0.12	80	-0.21	20	100
Tie2/Ang1/GRB2	-0.25	0.48	-10000	0	-0.96	143	143
MAPK3	-0.24	0.42	-10000	0	-0.88	142	142
MAPK1	-0.24	0.42	-10000	0	-0.88	141	141
Tie2/Ang1/GRB7	-0.25	0.48	-10000	0	-0.97	143	143
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.26	0.46	-10000	0	-0.95	143	143
PI3K	-0.24	0.44	-10000	0	-0.91	142	142
FES	-0.25	0.47	-10000	0	-0.95	143	143
Crk/Dok-R	-0.23	0.45	-10000	0	-0.9	143	143
Tie2/Ang1/ABIN2	-0.26	0.48	-10000	0	-0.97	143	143
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.18	0.35	-10000	0	-0.72	142	142
STAT5A	0.026	0.005	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.18	0.38	0.4	1	-0.76	135	136
Tie2/Ang2	-0.22	0.4	-10000	0	-0.84	133	133
Tie2/Ang1	-0.27	0.49	-10000	0	-1	143	143
FOXO1	-0.18	0.35	-10000	0	-0.72	137	137
ELF1	0.009	0.045	-10000	0	-0.18	15	15
ELF2	-0.25	0.45	-10000	0	-0.92	142	142
mol:Choline	-0.25	0.43	-10000	0	-0.9	143	143
cell migration	-0.059	0.1	-10000	0	-0.22	137	137
FYN	-0.19	0.34	-10000	0	-0.71	136	136
DOK2	0.019	0.023	0.17	3	-0.31	1	4
negative regulation of cell cycle	-0.13	0.25	-10000	0	-0.52	128	128
ETS1	-0.046	0.13	0.18	1	-0.26	131	132
PXN	-0.14	0.32	0.42	7	-0.64	131	138
ITGB1	0.026	0.004	-10000	0	-10000	0	0
NOS3	-0.17	0.33	0.44	1	-0.68	137	138
RAC1	0.025	0.008	-10000	0	-10000	0	0
TNF	-0.063	0.15	0.18	11	-0.28	156	167
MAPKKK cascade	-0.25	0.43	-10000	0	-0.9	143	143
RASA1	0.025	0.016	-10000	0	-0.31	1	1
Tie2/Ang1/Shc	-0.25	0.47	-10000	0	-0.96	143	143
NCK1	0.025	0.007	-10000	0	-10000	0	0
vasculogenesis	-0.13	0.27	0.43	1	-0.54	137	138
mol:Phosphatidic acid	-0.25	0.43	-10000	0	-0.9	143	143
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.14	0.29	0.43	1	-0.6	137	138
Rac1/GTP	-0.18	0.35	-10000	0	-0.72	139	139
MMP2	-0.26	0.46	-10000	0	-0.95	143	143

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.15	0.37	-10000	0	-0.82	108	108
MKNK1	0.027	0.004	-10000	0	-10000	0	0
MAPK14	-0.033	0.14	-10000	0	-0.3	106	106
ATF2/c-Jun	-0.052	0.15	-10000	0	-0.3	100	100
MAPK11	-0.032	0.14	0.2	5	-0.3	104	109
MITF	-0.052	0.17	-10000	0	-0.37	101	101
MAPKAPK5	-0.049	0.16	-10000	0	-0.35	101	101
KRT8	-0.047	0.16	-10000	0	-0.35	100	100
MAPKAPK3	0.026	0.005	-10000	0	-10000	0	0
MAPKAPK2	0.026	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.046	0.21	-10000	0	-0.43	106	106
CEBPB	-0.046	0.16	-10000	0	-0.35	99	99
SLC9A1	-0.051	0.16	-10000	0	-0.35	105	105
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.068	0.19	-10000	0	-0.37	122	122
p38alpha-beta/MNK1	-0.02	0.18	-10000	0	-0.35	101	101
JUN	-0.053	0.14	-10000	0	-0.42	39	39
PPARGC1A	-0.13	0.24	-10000	0	-0.4	175	175
USF1	-0.051	0.16	-10000	0	-0.36	102	102
RAB5/GDP/GDI1	-0.026	0.12	-10000	0	-0.26	98	98
NOS2	-0.079	0.25	-10000	0	-0.5	100	100
DDIT3	-0.05	0.16	-10000	0	-0.35	104	104
RAB5A	0.026	0.005	-10000	0	-10000	0	0
HSPB1	-0.038	0.14	0.28	21	-0.3	86	107
p38alpha-beta/HBP1	-0.018	0.17	-10000	0	-0.34	96	96
CREB1	-0.054	0.17	0.21	1	-0.38	101	102
RAB5/GDP	0.019	0.004	-10000	0	-10000	0	0
EIF4E	-0.049	0.14	0.22	1	-0.32	101	102
RPS6KA4	-0.048	0.16	0.26	1	-0.35	103	104
PLA2G4A	-0.057	0.15	0.22	1	-0.34	105	106
GDI1	-0.05	0.16	-10000	0	-0.35	105	105
TP53	-0.071	0.18	-10000	0	-0.44	97	97
RPS6KA5	-0.055	0.17	-10000	0	-0.36	105	105
ESR1	-0.06	0.18	-10000	0	-0.37	112	112
HBP1	0.025	0.008	-10000	0	-10000	0	0
MEF2C	-0.058	0.18	-10000	0	-0.38	107	107
MEF2A	-0.053	0.16	-10000	0	-0.36	104	104
EIF4EBP1	-0.064	0.19	0.21	1	-0.43	99	100
KRT19	-0.073	0.2	-10000	0	-0.39	122	122
ELK4	-0.05	0.16	-10000	0	-0.35	101	101
ATF6	-0.051	0.16	-10000	0	-0.36	103	103
ATF1	-0.053	0.17	0.21	1	-0.38	100	101
p38alpha-beta/MAPKAPK2	-0.02	0.17	-10000	0	-0.34	103	103
p38alpha-beta/MAPKAPK3	-0.019	0.17	-10000	0	-0.35	101	101

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.031	0.027	0.17	16	-10000	0	16
GPC2	0.055	0.064	0.17	104	-0.31	1	105
GPC2/Midkine	0.061	0.056	0.15	112	-0.16	2	114
neuron projection morphogenesis	0.061	0.056	0.15	112	-0.16	2	114

×

Endothelins

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
AKT1	-0.04	0.14	0.26	23	-0.27	102	125
PTK2B	0.019	0.012	-10000	0	-10000	0	0
mol:Ca2+	-0.16	0.39	0.38	1	-0.92	95	96
EDN1	-0.007	0.11	0.2	35	-0.22	80	115
EDN3	-0.091	0.16	0.17	2	-0.31	172	174
EDN2	0.015	0.073	0.17	11	-0.31	22	33
HRAS/GDP	-0.076	0.2	0.28	5	-0.45	80	85
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.042	0.16	0.21	2	-0.38	64	66
ADCY4	-0.064	0.16	0.2	31	-0.34	87	118
ADCY5	-0.075	0.18	0.2	29	-0.38	99	128
ADCY6	-0.062	0.16	0.21	30	-0.34	85	115
ADCY7	-0.062	0.15	0.19	26	-0.33	86	112
ADCY1	-0.056	0.16	0.19	26	-0.34	83	109
ADCY2	-0.063	0.16	0.2	29	-0.35	87	116
ADCY3	-0.062	0.16	0.2	29	-0.33	86	115
ADCY8	-0.06	0.14	0.18	17	-0.32	77	94
ADCY9	-0.061	0.16	0.2	30	-0.34	84	114
arachidonic acid secretion	-0.13	0.29	0.31	7	-0.55	124	131
ETB receptor/Endothelin-1/Gq/GTP	-0.041	0.14	-10000	0	-0.3	85	85
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
HRAS	0.028	0.017	0.17	6	-10000	0	6
ETA receptor/Endothelin-1/G12/GTP	0.001	0.15	0.33	20	-0.25	95	115
ETA receptor/Endothelin-1/Gs/GTP	-0.038	0.18	0.31	19	-0.29	130	149
mol:GTP	-0.002	0.007	-10000	0	-10000	0	0
COL3A1	-0.038	0.15	0.26	25	-0.34	56	81
EDNRB	-0.01	0.1	0.18	1	-0.31	51	52
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.06	0.18	0.25	17	-0.44	77	94
CYSLTR1	-0.052	0.17	0.25	24	-0.33	101	125
SLC9A1	-0.019	0.091	0.18	23	-0.21	51	74
mol:GDP	-0.087	0.21	0.28	8	-0.48	83	91
SLC9A3	-0.16	0.4	-10000	0	-0.83	105	105
RAF1	-0.095	0.22	0.28	9	-0.46	101	110
JUN	-0.11	0.29	-10000	0	-0.72	70	70
JAK2	-0.041	0.15	0.25	23	-0.28	102	125
mol:IP3	-0.044	0.15	0.22	1	-0.4	52	53
ETA receptor/Endothelin-1	-0.024	0.19	0.38	23	-0.31	109	132
PLCB1	0.022	0.031	-10000	0	-0.31	4	4
PLCB2	0.021	0.02	0.17	2	-10000	0	2
ETA receptor/Endothelin-3	-0.078	0.16	0.19	2	-0.26	184	186
FOS	-0.16	0.35	0.37	4	-0.88	86	90
Gai/GDP	-0.17	0.37	-10000	0	-0.78	122	122
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:Ca ++	-0.071	0.2	0.23	18	-0.46	73	91
BCAR1	0.022	0.011	-10000	0	-10000	0	0
PRKCB1	-0.048	0.15	0.2	2	-0.38	57	59
GNAQ	0.015	0.023	-10000	0	-10000	0	0
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
GNAL	-0.054	0.14	-10000	0	-0.31	117	117
Gs family/GDP	-0.1	0.22	0.27	6	-0.46	104	110
ETA receptor/Endothelin-1/Gq/GTP	-0.047	0.16	0.18	18	-0.37	76	94
MAPK14	-0.045	0.13	0.21	1	-0.31	69	70
TRPC6	-0.18	0.42	0.38	1	-1	95	96
GNAI2	0.026	0.005	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.04	0.14	-10000	0	-0.32	70	70
ETB receptor/Endothelin-2	0.002	0.092	-10000	0	-0.22	71	71
ETB receptor/Endothelin-3	-0.067	0.14	0.14	1	-0.24	185	186
ETB receptor/Endothelin-1	-0.009	0.12	0.19	4	-0.25	76	80
MAPK3	-0.15	0.32	0.38	4	-0.78	90	94
MAPK1	-0.15	0.33	0.37	4	-0.78	92	96
Rac1/GDP	-0.074	0.2	0.29	5	-0.44	78	83
cAMP biosynthetic process	-0.053	0.18	0.29	20	-0.37	88	108
MAPK8	-0.14	0.36	-10000	0	-0.75	102	102
SRC	0.026	0.006	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.059	0.16	0.16	2	-0.37	88	90
p130Cas/CRK/Src/PYK2	-0.14	0.28	0.3	7	-0.63	101	108
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.074	0.2	0.29	5	-0.45	77	82
COL1A2	-0.05	0.17	0.25	16	-0.42	62	78
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.007	0.12	0.22	3	-0.24	73	76
mol:DAG	-0.044	0.15	0.22	1	-0.4	52	53
MAP2K2	-0.12	0.26	0.32	6	-0.6	95	101
MAP2K1	-0.12	0.26	0.35	5	-0.6	95	100
EDNRA	-0.028	0.14	0.21	24	-0.31	70	94
positive regulation of muscle contraction	-0.028	0.13	0.22	39	-0.25	87	126
Gq family/GDP	-0.065	0.2	0.25	1	-0.44	85	86
HRAS/GTP	-0.078	0.2	0.27	6	-0.43	81	87
PRKCH	-0.048	0.15	0.21	3	-0.39	53	56
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.054	0.16	0.21	3	-0.4	59	62
PRKCB	-0.072	0.18	0.21	6	-0.43	77	83
PRKCE	-0.045	0.14	0.25	3	-0.38	51	54
PRKCD	-0.049	0.15	0.21	5	-0.39	53	58
PRKCG	-0.051	0.15	0.21	5	-0.39	55	60
regulation of vascular smooth muscle contraction	-0.19	0.41	0.4	3	-1.1	86	89
PRKCQ	-0.055	0.16	0.21	1	-0.43	53	54
PLA2G4A	-0.15	0.33	0.31	7	-0.61	124	131
GNA14	0.014	0.028	-10000	0	-0.31	1	1
GNA15	0.005	0.07	-10000	0	-0.31	21	21
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA11	0.009	0.06	-10000	0	-0.31	15	15
Rac1/GTP	0.001	0.15	0.33	20	-0.25	100	120
MMP1	-0.008	0.18	0.28	21	-0.67	28	49

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.075	0.1	0.26	56	-0.25	1	57
SMARCC2	0.01	0.044	-10000	0	-0.11	41	41
SMARCC1	0.009	0.045	-10000	0	-0.11	45	45
TBX21	-0.079	0.16	0.43	2	-0.37	79	81
SUMO2	0.029	0.02	-10000	0	-10000	0	0
STAT1 (dimer)	0.034	0.021	0.19	8	-10000	0	8
FKBP4	0.025	0.007	-10000	0	-10000	0	0
FKBP5	0.026	0.016	-10000	0	-0.31	1	1
GR alpha/HSP90/FKBP51/HSP90	0.1	0.12	0.28	97	-10000	0	97
PRL	-0.066	0.12	-10000	0	-0.46	4	4
cortisol/GR alpha (dimer)/TIF2	0.12	0.24	0.5	109	-10000	0	109
RELA	-0.028	0.1	-10000	0	-0.2	113	113
FGG	0.16	0.23	0.44	158	-0.3	1	159
GR beta/TIF2	0.049	0.14	0.28	83	-0.24	29	112
IFNG	-0.21	0.29	0.37	1	-0.62	131	132
apoptosis	0.1	0.2	0.52	67	-0.46	1	68
CREB1	0.002	0.1	-10000	0	-0.28	51	51
histone acetylation	-0.053	0.17	0.31	17	-0.38	71	88
BGLAP	-0.09	0.15	-10000	0	-0.43	36	36
GR/PKAc	0.11	0.11	0.29	78	-10000	0	78
NF kappa B1 p50/RelA	-0.046	0.18	-10000	0	-0.33	127	127
SMARCD1	0.01	0.045	-10000	0	-0.11	46	46
MDM2	0.084	0.11	0.22	148	-10000	0	148
GATA3	-0.065	0.15	-10000	0	-0.31	139	139
AKT1	0.023	0.004	-10000	0	-10000	0	0
CSF2	-0.07	0.13	-10000	0	-0.49	14	14
GSK3B	0.028	0.019	-10000	0	-10000	0	0
NR1I3	0.1	0.2	0.52	56	-0.68	3	59
CSN2	0.13	0.19	0.37	151	-0.26	1	152
BRG1/BAF155/BAF170/BAF60A	0.017	0.13	-10000	0	-0.3	67	67
NFATC1	0.025	0.009	-10000	0	-10000	0	0
POU2F1	0.026	0.007	-10000	0	-10000	0	0
CDKN1A	-0.028	0.14	-10000	0	-1.4	4	4
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.005	0.014	-10000	0	-10000	0	0
SFN	-0.006	0.1	-10000	0	-0.31	49	49
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.11	0.29	73	-0.18	2	75
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.064	0.26	0.48	64	-0.66	33	97
JUN	-0.12	0.18	0.29	1	-0.38	128	129
IL4	-0.088	0.15	-10000	0	-0.42	44	44
CDK5R1	0.036	0.033	0.18	23	-10000	0	23
PRKACA	0.027	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.071	0.11	0.18	24	-0.25	95	119
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.12	0.11	0.29	88	-10000	0	88
cortisol/GR alpha (monomer)	0.21	0.31	0.58	163	-0.34	1	164
NCOA2	-0.015	0.1	-10000	0	-0.31	53	53
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.068	0.14	0.2	4	-0.32	95	99
AP-1/NFAT1-c-4	-0.21	0.29	-10000	0	-0.55	176	176
AFP	-0.087	0.14	-10000	0	-0.5	6	6
SUV420H1	0.026	0.006	-10000	0	-10000	0	0
IRF1	0.13	0.16	0.39	91	-10000	0	91
TP53	0.032	0.014	-10000	0	-10000	0	0
PPP5C	0.027	0.003	-10000	0	-10000	0	0
KRT17	-0.32	0.44	-10000	0	-0.94	143	143
KRT14	-0.35	0.53	0.35	3	-1.1	147	150
TBP	0.031	0.013	-10000	0	-0.21	1	1
CREBBP	0.054	0.14	0.26	108	-0.26	38	146
HDAC1	0.026	0.007	-10000	0	-10000	0	0
HDAC2	0.023	0.009	-10000	0	-10000	0	0
AP-1	-0.21	0.29	-10000	0	-0.55	176	176
MAPK14	0.029	0.017	-10000	0	-10000	0	0
MAPK10	0.026	0.035	-10000	0	-0.3	4	4
MAPK11	0.032	0.027	0.17	8	-10000	0	8
KRT5	-0.41	0.5	-10000	0	-1	188	188
interleukin-1 receptor activity	0	0.001	-10000	0	-10000	0	0
NCOA1	0.028	0.004	-10000	0	-10000	0	0
STAT1	0.034	0.021	0.19	8	-10000	0	8
CGA	-0.15	0.3	-10000	0	-0.79	75	75
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.069	0.17	0.36	93	-0.33	20	113
MAPK3	0.029	0.019	-10000	0	-10000	0	0
MAPK1	0.029	0.017	-10000	0	-10000	0	0
ICAM1	-0.15	0.24	-10000	0	-0.52	112	112
NFKB1	-0.03	0.11	-10000	0	-0.2	113	113
MAPK8	-0.11	0.18	0.34	2	-0.34	147	149
MAPK9	0.028	0.017	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.1	0.2	0.52	67	-0.48	1	68
BAX	-0.02	0.076	-10000	0	-10000	0	0
POMC	-0.24	0.45	0.42	1	-1.4	59	60
EP300	0.053	0.14	0.26	112	-0.27	41	153
cortisol/GR alpha (dimer)/p53	0.16	0.25	0.52	126	-10000	0	126
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.088	0.19	92	-10000	0	92
SGK1	-0.063	0.45	0.48	2	-1.1	71	73
IL13	-0.28	0.36	-10000	0	-0.77	149	149
IL6	-0.24	0.39	0.31	1	-0.82	130	131
PRKACG	0.019	0.005	-10000	0	-10000	0	0
IL5	-0.24	0.3	-10000	0	-0.66	140	140
IL2	-0.22	0.29	-10000	0	-0.63	134	134
CDK5	0.027	0.011	-10000	0	-10000	0	0
PRKACB	0.026	0.005	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
IL8	-0.18	0.31	-10000	0	-0.65	116	116
CDK5R1/CDK5	0.045	0.032	0.16	22	-10000	0	22
NF kappa B1 p50/RelA/PKAc	-0.007	0.16	-10000	0	-0.27	98	98
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.17	0.24	0.49	147	-10000	0	147
SMARCA4	0.01	0.045	-10000	0	-0.13	28	28
chromatin remodeling	0.068	0.2	0.36	95	-0.37	24	119
NF kappa B1 p50/RelA/Cbp	-0.008	0.22	0.34	41	-0.39	78	119
JUN (dimer)	-0.12	0.18	0.29	1	-0.38	128	129
YWHAH	0.027	0.004	-10000	0	-10000	0	0
VIPR1	-0.074	0.15	0.33	3	-0.36	66	69
NR3C1	0.14	0.2	0.39	142	-10000	0	142
NR4A1	-0.024	0.16	-10000	0	-0.43	60	60
TIF2/SUV420H1	0.004	0.078	-10000	0	-0.21	53	53
MAPKKK cascade	0.1	0.2	0.52	67	-0.46	1	68
cortisol/GR alpha (dimer)/Src-1	0.19	0.26	0.5	162	-10000	0	162
PBX1	0.026	0.016	-10000	0	-0.31	1	1
POU1F1	0.021	0.014	0.18	3	-10000	0	3
SELE	-0.25	0.39	-10000	0	-0.84	133	133
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.068	0.2	0.36	94	-0.37	24	118
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.17	0.24	0.49	147	-10000	0	147
mol:cortisol	0.13	0.19	0.34	175	-0.19	1	176
MMP1	-0.1	0.28	-10000	0	-0.98	42	42

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.009	0.1	0.22	91	-0.19	1	92
KIRREL	-0.036	0.13	-10000	0	-0.32	91	91
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.009	0.11	0.19	1	-0.22	91	92
PLCG1	0.026	0.005	-10000	0	-10000	0	0
ARRB2	0.025	0.008	-10000	0	-10000	0	0
WASL	0.025	0.008	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.021	0.095	0.23	1	-0.17	90	91
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.015	0.078	-10000	0	-0.19	80	80
FYN	-0.028	0.068	0.22	12	-0.16	72	84
mol:Ca2+	0.019	0.092	0.22	1	-0.17	89	90
mol:DAG	0.02	0.093	0.22	1	-0.17	89	90
NPHS2	-0.003	0.033	0.18	3	-10000	0	3
mol:IP3	0.02	0.093	0.22	1	-0.17	89	90
regulation of endocytosis	0.006	0.079	-10000	0	-0.15	92	92
Nephrin/NEPH1/podocin/Cholesterol	0.01	0.087	0.21	1	-0.16	91	92
establishment of cell polarity	-0.009	0.1	0.19	1	-0.22	91	92
Nephrin/NEPH1/podocin/NCK1-2	0.03	0.092	0.23	1	-0.16	86	87
Nephrin/NEPH1/beta Arrestin2	0.008	0.081	-10000	0	-0.15	92	92
NPHS1	0.004	0.042	0.19	11	-10000	0	11
Nephrin/NEPH1/podocin	0.007	0.083	0.17	1	-0.16	92	93
TJP1	0.026	0.005	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
NCK2	0.027	0.003	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.021	0.094	0.23	1	-0.17	89	90
CD2AP	0.027	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.022	0.094	0.23	1	-0.17	88	89
GRB2	0.026	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.05	0.095	0.22	12	-0.2	116	128
cytoskeleton organization	-0.028	0.075	0.2	3	-0.2	77	80
Nephrin/NEPH1	0	0.074	0.13	10	-0.15	91	101
Nephrin/NEPH1/ZO-1	0.01	0.091	0.18	1	-0.18	89	90

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.22	0.51	-10000	0	-1.2	82	82
IL23A	-0.23	0.52	-10000	0	-1.2	83	83
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.52	-10000	0	-1.1	100	100
positive regulation of T cell mediated cytotoxicity	-0.24	0.58	-10000	0	-1.2	101	101
ITGA3	-0.22	0.5	-10000	0	-1.2	81	81
IL17F	-0.14	0.32	0.42	2	-0.67	100	102
IL12B	0.014	0.07	0.22	24	-0.14	1	25
STAT1 (dimer)	-0.23	0.56	0.59	1	-1.2	101	102
CD4	-0.2	0.48	-10000	0	-1.1	77	77
IL23	-0.22	0.51	0.61	1	-1.2	83	84
IL23R	-0.022	0.16	-10000	0	-0.82	11	11
IL1B	-0.25	0.56	-10000	0	-1.3	85	85
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.2	0.48	-10000	0	-1.1	76	76
TYK2	0.006	0.043	-10000	0	-10000	0	0
STAT4	0.028	0.039	0.17	13	-0.31	4	17
STAT3	0.026	0.005	-10000	0	-10000	0	0
IL18RAP	0.022	0.064	0.17	16	-0.3	15	31
IL12RB1	0.008	0.067	0.2	16	-0.34	6	22
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
IL12Rbeta1/TYK2	0.011	0.067	0.18	13	-0.26	6	19
IL23R/JAK2	-0.014	0.17	-10000	0	-0.84	8	8
positive regulation of chronic inflammatory response	-0.24	0.58	-10000	0	-1.2	101	101
natural killer cell activation	0.002	0.008	-10000	0	-10000	0	0
JAK2	0.008	0.054	-10000	0	-0.32	1	1
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
NFKB1	0.023	0.013	-10000	0	-10000	0	0
RELA	0.023	0.014	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.2	0.48	0.61	1	-1.1	85	86
ALOX12B	-0.21	0.5	-10000	0	-1.1	84	84
CXCL1	-0.3	0.6	0.66	1	-1.2	128	129
T cell proliferation	-0.24	0.58	-10000	0	-1.2	101	101
NFKBIA	0.023	0.014	-10000	0	-10000	0	0
IL17A	-0.088	0.26	0.42	3	-0.54	83	86
PI3K	-0.21	0.52	-10000	0	-1.1	99	99
IFNG	0	0.028	0.088	1	-0.099	9	10
STAT3 (dimer)	-0.2	0.5	0.54	1	-1	99	100
IL18R1	0.024	0.037	-10000	0	-0.3	6	6
IL23/IL23R/JAK2/TYK2/SOCS3	-0.12	0.33	0.42	2	-0.73	77	79
IL18/IL18R	0.046	0.063	0.16	6	-0.19	27	33
macrophage activation	-0.011	0.021	0.036	3	-0.044	83	86
TNF	-0.24	0.54	-10000	0	-1.3	80	80
STAT3/STAT4	-0.21	0.53	0.57	1	-1.1	100	101
STAT4 (dimer)	-0.23	0.56	0.59	1	-1.2	100	101
IL18	0.018	0.052	-10000	0	-0.3	12	12
IL19	-0.2	0.48	-10000	0	-1.1	76	76
STAT5A (dimer)	-0.23	0.55	-10000	0	-1.2	103	103
STAT1	0.029	0.019	0.17	8	-10000	0	8
SOCS3	-0.012	0.11	0.17	6	-0.31	58	64
CXCL9	-0.2	0.49	0.66	1	-1.1	77	78
MPO	-0.24	0.54	-10000	0	-1.2	98	98
positive regulation of humoral immune response	-0.24	0.58	-10000	0	-1.2	101	101
IL23/IL23R/JAK2/TYK2	-0.27	0.66	-10000	0	-1.4	101	101
IL6	-0.29	0.61	-10000	0	-1.2	129	129
STAT5A	0.026	0.005	-10000	0	-10000	0	0
IL2	0.015	0.024	0.17	2	-10000	0	2
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-10000	0	-10000	0	0
CD3E	-0.2	0.49	-10000	0	-1.2	77	77
keratinocyte proliferation	-0.24	0.58	-10000	0	-1.2	101	101
NOS2	-0.23	0.52	-10000	0	-1.2	89	89

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.041	0.025	0.14	21	-10000	0	21
VLDLR	0.026	0.016	-10000	0	-0.31	1	1
CRKL	0.026	0.005	-10000	0	-10000	0	0
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
FYN	0.022	0.018	-10000	0	-0.31	1	1
ITGA3	0.02	0.047	-10000	0	-0.31	10	10
RELN/VLDLR/Fyn	0.049	0.047	-10000	0	-0.18	6	6
MAPK8IP1/MKK7/MAP3K11/JNK1	0.064	0.046	-10000	0	-0.16	12	12
AKT1	-0.053	0.094	0.14	2	-0.18	152	154
MAP2K7	0.027	0.004	-10000	0	-10000	0	0
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0
DAB1	-0.095	0.16	0.17	2	-0.31	178	180
RELN/LRP8/DAB1	-0.02	0.11	0.23	2	-0.17	160	162
LRPAP1/LRP8	0.04	0.015	0.14	6	-10000	0	6
RELN/LRP8/DAB1/Fyn	-0.011	0.11	0.2	5	-0.16	158	163
DAB1/alpha3/beta1 Integrin	-0.016	0.1	-10000	0	-0.16	144	144
long-term memory	-0.039	0.13	0.33	1	-0.18	189	190
DAB1/LIS1	-0.005	0.11	0.22	1	-0.16	141	142
DAB1/CRLK/C3G	-0.014	0.1	-10000	0	-0.16	141	141
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
DAB1/NCK2	-0.004	0.11	0.23	1	-0.16	149	150
ARHGEF2	0.026	0.006	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.041	0.13	0.17	1	-0.31	99	100
CDK5R1	0.034	0.031	0.17	23	-10000	0	23
RELN	0.04	0.059	0.17	60	-0.31	4	64
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
RELN/LRP8/Fyn	0.051	0.048	0.24	3	-0.16	6	9
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.036	0.14	-10000	0	-0.19	200	200
MAPK8	0.018	0.052	-10000	0	-0.31	12	12
RELN/VLDLR/DAB1	-0.022	0.11	-10000	0	-0.17	161	161
ITGB1	0.026	0.004	-10000	0	-10000	0	0
MAP1B	-0.061	0.092	0.17	13	-0.19	144	157
RELN/LRP8	0.057	0.045	0.24	3	-0.17	4	7
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.008	0.11	0.24	2	-0.16	150	152
PI3K	0.031	0.034	-10000	0	-0.24	6	6
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.034	0.035	-10000	0	-0.21	9	9
RAP1A	-0.045	0.1	0.33	14	-0.25	1	15
PAFAH1B1	0.025	0.007	-10000	0	-10000	0	0
MAPK8IP1	0.026	0.009	0.17	1	-10000	0	1
CRLK/C3G	0.037	0.011	-10000	0	-10000	0	0
GRIN2B	0.018	0.01	0.17	1	-10000	0	1
NCK2	0.027	0.003	-10000	0	-10000	0	0
neuron differentiation	-0.044	0.1	0.19	1	-0.25	50	51
neuron adhesion	-0.048	0.11	0.34	16	-0.28	6	22
LRP8	0.028	0.018	0.17	7	-10000	0	7
GSK3B	-0.052	0.089	0.15	3	-0.18	147	150
RELN/VLDLR/DAB1/Fyn	-0.013	0.11	-10000	0	-0.16	160	160
MAP3K11	0.026	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.049	0.1	0.15	2	-0.19	156	158
CDK5	0.025	0.008	-10000	0	-10000	0	0
MAPT	0.004	0.059	0.75	3	-10000	0	3
neuron migration	-0.06	0.11	0.28	9	-0.22	101	110
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.044	0.1	0.19	1	-0.25	49	50
RELN/VLDLR	0.07	0.051	0.25	3	-0.16	5	8

×

Integrins in angiogenesis

Figure S10. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S10. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.016	0.078	0.14	5	-0.23	44	49
alphaV beta3 Integrin	-0.002	0.11	-10000	0	-0.22	92	92
PTK2	-0.082	0.18	0.29	11	-0.39	103	114
IGF1R	0.026	0.017	0.17	1	-0.31	1	2
PI4KB	0.026	0.006	-10000	0	-10000	0	0
MFGE8	0.025	0.026	-10000	0	-0.31	3	3
SRC	0.026	0.006	-10000	0	-10000	0	0
CDKN1B	-0.042	0.15	-10000	0	-0.4	62	62
VEGFA	0.01	0.077	0.17	5	-0.31	26	31
ILK	-0.032	0.14	-10000	0	-0.42	47	47
ROCK1	0.025	0.016	-10000	0	-0.31	1	1
AKT1	-0.036	0.12	-10000	0	-0.39	47	47
PTK2B	-0.038	0.072	0.17	4	-0.2	67	71
alphaV/beta3 Integrin/JAM-A	-0.006	0.12	0.25	1	-0.2	121	122
CBL	0.025	0.016	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.029	0.12	-10000	0	-0.19	94	94
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.047	0.078	0.25	1	-0.2	40	41
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.042	0.12	-10000	0	-0.31	51	51
alphaV/beta3 Integrin/Syndecan-1	0	0.1	-10000	0	-0.19	102	102
PI4KA	0.026	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.007	0.13	-10000	0	-0.24	100	100
PI4 Kinase	0.037	0.011	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
alphaV/beta3 Integrin/Osteopontin	0.017	0.1	-10000	0	-0.18	90	90
RPS6KB1	-0.055	0.12	0.4	5	-0.34	43	48
TLN1	0.026	0.005	-10000	0	-10000	0	0
MAPK3	-0.09	0.2	-10000	0	-0.44	101	101
GPR124	0.014	0.048	-10000	0	-0.31	10	10
MAPK1	-0.091	0.2	-10000	0	-0.44	103	103
PXN	0.026	0.006	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
alphaV/beta3 Integrin/Tumstatin	-0.003	0.11	-10000	0	-0.21	101	101
cell adhesion	0.004	0.1	-10000	0	-0.21	87	87
ANGPTL3	0.083	0.073	0.17	193	-10000	0	193
VEGFR2 homodimer/VEGFA homodimer/Src	0.03	0.073	-10000	0	-0.19	44	44
IGF-1R heterotetramer	0.026	0.017	0.17	1	-0.31	1	2
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
TGFBR2	0.019	0.05	-10000	0	-0.31	11	11
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
IGF1	0.008	0.089	0.17	17	-0.31	33	50
RAC1	0.025	0.008	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.001	0.09	-10000	0	-0.18	86	86
apoptosis	0.026	0.005	-10000	0	-10000	0	0
CD47	0.026	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.008	0.089	-10000	0	-0.18	89	89
VCL	0.01	0.072	-10000	0	-0.31	24	24
alphaV/beta3 Integrin/Del1	-0.028	0.14	-10000	0	-0.25	126	126
CSF1	0.019	0.05	-10000	0	-0.31	11	11
PIK3C2A	-0.03	0.13	-10000	0	-0.41	45	45
PI4 Kinase/Pyk2	-0.032	0.11	-10000	0	-0.22	100	100
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.006	0.11	-10000	0	-0.19	110	110
FAK1/Vinculin	-0.06	0.16	0.28	14	-0.34	94	108
alphaV beta3/Integrin/ppsTEM5	0.001	0.09	-10000	0	-0.18	86	86
RHOA	0.026	0.005	-10000	0	-10000	0	0
VTN	0.007	0.12	0.17	51	-0.31	51	102
BCAR1	0.022	0.011	-10000	0	-10000	0	0
FGF2	0.005	0.082	0.17	1	-0.31	31	32
F11R	-0.023	0.046	-10000	0	-0.21	27	27
alphaV/beta3 Integrin/Lactadherin	0.008	0.092	-10000	0	-0.18	89	89
alphaV/beta3 Integrin/TGFBR2	0.006	0.097	-10000	0	-0.2	87	87
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.049	0.044	-10000	0	-0.17	11	11
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.009	0.081	-10000	0	-0.16	89	89
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.02	0.052	0.17	4	-0.31	11	15
alphaV/beta3 Integrin/Pyk2	-0.013	0.093	0.18	2	-0.18	107	109
SDC1	0.013	0.066	-10000	0	-0.31	20	20
VAV3	-0.027	0.058	0.2	7	-0.19	39	46
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
IRS1	0.017	0.058	-10000	0	-0.31	15	15
FAK1/Paxillin	-0.059	0.16	0.29	11	-0.33	92	103
cell migration	-0.062	0.14	0.24	12	-0.31	93	105
ITGAV	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.001	0.12	0.23	1	-0.2	102	103
SPP1	0.045	0.058	0.17	69	-0.31	3	72
KDR	0.012	0.069	-10000	0	-0.31	22	22
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.005	-10000	0	-10000	0	0
COL4A3	0.007	0.079	0.17	1	-0.31	29	30
angiogenesis	-0.099	0.21	0.25	2	-0.46	103	105
Rac1/GTP	0.005	0.061	0.17	7	-0.18	37	44
EDIL3	-0.037	0.13	0.17	1	-0.31	92	93
cell proliferation	0.005	0.096	-10000	0	-0.19	87	87

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.026	0.028	0.17	7	-0.31	2	9
GNB1/GNG2	-0.045	0.078	-10000	0	-0.18	111	111
AKT1	-0.023	0.11	0.27	5	-0.23	26	31
EGF	0.023	0.084	0.17	40	-0.31	23	63
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.01	0.075	0.26	18	-0.24	5	23
mol:Ca2+	-0.049	0.15	0.3	6	-0.3	113	119
LYN	-0.012	0.058	0.28	9	-0.23	4	13
RhoA/GTP	-0.022	0.061	-10000	0	-0.13	97	97
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.057	0.17	0.32	12	-0.34	109	121
GNG2	0.023	0.037	-10000	0	-0.31	6	6
ARRB2	0.025	0.008	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.016	0.13	0.27	1	-0.37	45	46
G beta5/gamma2	-0.054	0.11	-10000	0	-0.24	110	110
PRKCH	-0.059	0.17	0.32	7	-0.34	110	117
DNM1	0.025	0.018	0.17	1	-0.31	1	2
TXA2/TP beta/beta Arrestin3	0.011	0.017	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.005	0.083	0.17	1	-0.31	32	33
G12 family/GTP	-0.058	0.13	-10000	0	-0.3	103	103
ADRBK1	0.026	0.006	-10000	0	-10000	0	0
ADRBK2	0.026	0.016	-10000	0	-0.31	1	1
RhoA/GTP/ROCK1	0.033	0.014	-10000	0	-0.18	1	1
mol:GDP	0.028	0.11	0.32	30	-0.23	6	36
mol:NADP	0.026	0.018	0.17	6	-10000	0	6
RAB11A	0.027	0.003	-10000	0	-10000	0	0
PRKG1	-0.062	0.15	-10000	0	-0.31	129	129
mol:IP3	-0.065	0.18	0.34	5	-0.37	113	118
cell morphogenesis	0.033	0.013	-10000	0	-0.18	1	1
PLCB2	-0.094	0.24	0.38	4	-0.5	113	117
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.009	0.071	0.26	13	-0.23	8	21
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.013	0.07	0.28	11	-0.25	6	17
RHOA	0.026	0.005	-10000	0	-10000	0	0
PTGIR	0.037	0.052	0.17	44	-0.31	4	48
PRKCB1	-0.065	0.18	0.32	5	-0.36	112	117
GNAQ	0.026	0.006	-10000	0	-10000	0	0
mol:L-citrulline	0.026	0.018	0.17	6	-10000	0	6
TXA2/TXA2-R family	-0.099	0.24	0.38	4	-0.51	114	118
LCK	-0.011	0.067	0.25	13	-0.23	4	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.016	0.059	0.18	2	-0.18	28	30
TXA2-R family/G12 family/GDP/G beta/gamma	0.016	0.056	-10000	0	-0.4	7	7
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.016	0.057	-10000	0	-0.18	25	25
MAPK14	-0.035	0.12	0.26	16	-0.23	104	120
TGM2/GTP	-0.077	0.2	0.39	1	-0.42	107	108
MAPK11	-0.036	0.12	0.26	14	-0.23	106	120
ARHGEF1	-0.033	0.082	0.2	1	-0.18	101	102
GNAI2	0.026	0.005	-10000	0	-10000	0	0
JNK cascade	-0.068	0.18	0.32	6	-0.38	114	120
RAB11/GDP	0.027	0.004	-10000	0	-10000	0	0
ICAM1	-0.046	0.14	0.27	6	-0.28	111	117
cAMP biosynthetic process	-0.064	0.17	0.33	5	-0.35	107	112
Gq family/GTP/EBP50	0.006	0.063	0.24	11	-0.18	35	46
actin cytoskeleton reorganization	0.033	0.013	-10000	0	-0.18	1	1
SRC	-0.011	0.066	0.24	15	-0.23	4	19
GNB5	0.027	0.004	-10000	0	-10000	0	0
GNB1	0.027	0.004	-10000	0	-10000	0	0
EGF/EGFR	-0.016	0.099	0.3	20	-0.22	20	40
VCAM1	-0.05	0.14	0.27	6	-0.29	111	117
TP beta/Gq family/GDP/G beta5/gamma2	-0.016	0.13	0.27	1	-0.37	45	46
platelet activation	-0.047	0.15	0.33	14	-0.3	108	122
PGI2/IP	0.027	0.036	0.12	44	-0.21	4	48
PRKACA	0.004	0.052	-10000	0	-0.18	36	36
Gq family/GDP/G beta5/gamma2	-0.01	0.11	0.23	2	-0.32	44	46
TXA2/TP beta/beta Arrestin2	0.004	0.043	-10000	0	-0.33	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.008	0.053	0.19	1	-0.18	38	39
mol:DAG	-0.073	0.2	0.34	5	-0.41	112	117
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
TXA2/TP alpha	-0.09	0.22	0.4	4	-0.48	107	111
Gq family/GTP	-0.007	0.052	0.14	1	-0.16	47	48
YES1	-0.01	0.068	0.25	16	-0.23	4	20
GNAI2/GTP	0.003	0.053	-10000	0	-0.16	30	30
PGD2/DP	0.005	0.057	0.12	1	-0.21	32	33
SLC9A3R1	0.026	0.005	-10000	0	-10000	0	0
FYN	-0.01	0.065	0.24	15	-0.23	5	20
mol:NO	0.026	0.018	0.17	6	-10000	0	6
GNA15	0.012	0.068	-10000	0	-0.31	21	21
PGK/cGMP	-0.018	0.091	0.13	6	-0.18	117	123
RhoA/GDP	0.026	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.031	0.07	0.2	1	-0.21	20	21
NOS3	0.027	0.018	0.17	6	-10000	0	6
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.062	0.17	0.31	6	-0.35	113	119
PRKCB	-0.077	0.18	0.27	6	-0.38	115	121
PRKCE	-0.058	0.16	0.32	4	-0.34	108	112
PRKCD	-0.067	0.18	0.32	4	-0.37	109	113
PRKCG	-0.067	0.18	0.34	5	-0.38	112	117
muscle contraction	-0.092	0.22	0.38	5	-0.48	114	119
PRKCZ	-0.06	0.16	0.33	6	-0.34	113	119
ARR3	0.021	0.008	0.17	1	-10000	0	1
TXA2/TP beta	0.017	0.059	-10000	0	-0.17	33	33
PRKCQ	-0.064	0.17	0.35	4	-0.36	113	117
MAPKKK cascade	-0.086	0.21	0.35	5	-0.45	114	119
SELE	-0.067	0.17	0.27	6	-0.36	113	119
TP beta/GNAI2/GDP/G beta/gamma	0.03	0.068	0.2	1	-0.27	8	9
ROCK1	0.025	0.016	-10000	0	-0.31	1	1
GNA14	0.025	0.016	-10000	0	-0.31	1	1
chemotaxis	-0.12	0.27	0.39	3	-0.59	112	115
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
GNA11	0.016	0.058	-10000	0	-0.31	15	15
Rac1/GTP	0.018	0.006	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.015	0.065	0.13	3	-0.19	42	45
cell-cell adhesion	0.059	0.071	0.17	102	-10000	0	102
Ephrin B/EPHB2/RasGAP	0.035	0.088	-10000	0	-0.18	58	58
ITSN1	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
SHC1	0.026	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.033	0.022	0.13	3	-0.18	4	7
Ephrin B1/EPHB1	-0.027	0.097	-10000	0	-0.18	137	137
HRAS/GDP	-0.033	0.1	-10000	0	-0.23	57	57
Ephrin B/EPHB1/GRB7	-0.016	0.12	-10000	0	-0.18	158	158
Endophilin/SYNJ1	-0.026	0.064	0.19	9	-0.31	7	16
KRAS	0.025	0.007	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.015	0.12	-10000	0	-0.17	157	157
endothelial cell migration	0.044	0.036	-10000	0	-0.19	4	4
GRB2	0.026	0.005	-10000	0	-10000	0	0
GRB7	0.027	0.004	-10000	0	-10000	0	0
PAK1	-0.02	0.08	0.22	23	-0.39	5	28
HRAS	0.028	0.017	0.17	6	-10000	0	6
RRAS	-0.028	0.065	0.17	8	-0.32	8	16
DNM1	0.025	0.018	0.17	1	-0.31	1	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.052	0.097	0.2	21	-0.27	29	50
lamellipodium assembly	-0.059	0.071	-10000	0	-0.17	102	102
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.056	0.12	0.19	1	-0.23	126	127
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
EPHB2	0.025	0.032	0.17	3	-0.31	4	7
EPHB3	0.026	0.013	0.17	3	-10000	0	3
EPHB1	-0.069	0.15	-10000	0	-0.31	138	138
EPHB4	0.024	0.008	-10000	0	-10000	0	0
mol:GDP	-0.046	0.091	0.2	10	-0.24	59	69
Ephrin B/EPHB2	0.026	0.082	-10000	0	-0.17	58	58
Ephrin B/EPHB3	0.028	0.075	-10000	0	-0.16	53	53
JNK cascade	-0.045	0.098	0.31	18	-0.32	5	23
Ephrin B/EPHB1	-0.023	0.11	-10000	0	-0.17	164	164
RAP1/GDP	-0.024	0.11	0.25	13	-0.26	34	47
EFNB2	0.03	0.027	0.17	16	-10000	0	16
EFNB3	-0.016	0.11	-10000	0	-0.31	58	58
EFNB1	0.024	0.034	-10000	0	-0.31	5	5
Ephrin B2/EPHB1-2	-0.011	0.098	-10000	0	-0.16	137	137
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.029	0.12	-10000	0	-0.23	76	76
Rap1/GTP	-0.036	0.092	-10000	0	-0.27	27	27
axon guidance	0.014	0.065	0.13	3	-0.19	42	45
MAPK3	-0.062	0.11	0.18	3	-0.28	60	63
MAPK1	-0.063	0.11	0.18	2	-0.28	62	64
Rac1/GDP	-0.037	0.096	0.26	5	-0.23	58	63
actin cytoskeleton reorganization	-0.057	0.063	-10000	0	-0.2	47	47
CDC42/GDP	-0.032	0.1	0.24	14	-0.26	36	50
PI3K	0.049	0.038	0.17	1	-0.19	4	5
EFNA5	-0.003	0.094	0.17	1	-0.31	42	43
Ephrin B2/EPHB4	0.034	0.02	0.13	13	-10000	0	13
Ephrin B/EPHB2/Intersectin/N-WASP	-0.004	0.081	-10000	0	-0.22	51	51
CDC42	0.027	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.066	0.071	-10000	0	-0.26	27	27
PTK2	0.094	0.22	0.59	77	-10000	0	77
MAP4K4	-0.046	0.098	0.31	18	-0.32	5	23
SRC	0.026	0.006	-10000	0	-10000	0	0
KALRN	0.026	0.012	0.17	2	-10000	0	2
Intersectin/N-WASP	0.036	0.013	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.044	0.11	0.32	20	-0.29	22	42
MAP2K1	-0.06	0.11	0.17	1	-0.22	127	128
WASL	0.025	0.008	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.003	0.11	-10000	0	-0.17	136	136
cell migration	-0.075	0.14	0.28	11	-0.32	70	81
NRAS	0.026	0.016	-10000	0	-0.31	1	1
SYNJ1	-0.026	0.064	0.2	9	-0.31	7	16
PXN	0.026	0.006	-10000	0	-10000	0	0
TF	-0.047	0.081	0.17	3	-0.28	35	38
HRAS/GTP	-0.023	0.1	-10000	0	-0.18	116	116
Ephrin B1/EPHB1-2	-0.013	0.099	-10000	0	-0.17	137	137
cell adhesion mediated by integrin	0.018	0.061	0.18	33	-0.22	4	37
RAC1	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.024	0.11	-10000	0	-0.17	155	155
RAC1-CDC42/GTP	-0.065	0.072	-10000	0	-0.18	105	105
RASA1	0.025	0.016	-10000	0	-0.31	1	1
RAC1-CDC42/GDP	-0.031	0.097	0.27	3	-0.26	34	37
ruffle organization	-0.031	0.13	0.33	33	-0.29	20	53
NCK1	0.025	0.007	-10000	0	-10000	0	0
receptor internalization	-0.03	0.058	0.16	6	-0.3	8	14
Ephrin B/EPHB2/KALRN	0.038	0.084	-10000	0	-0.18	51	51
ROCK1	-0.004	0.044	0.18	24	-0.16	3	27
RAS family/GDP	-0.055	0.063	-10000	0	-0.21	44	44
Rac1/GTP	-0.062	0.074	-10000	0	-0.18	102	102
Ephrin B/EPHB1/Src/Paxillin	-0.062	0.13	-10000	0	-0.23	161	161

×

Aurora B 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.026	0.051	0.16	11	-0.18	10	21
STMN1	-0.02	0.028	0.24	1	-0.15	1	2
Aurora B/RasGAP/Survivin	0.091	0.099	0.24	113	-0.14	18	131
Chromosomal passenger complex/Cul3 protein complex	0.013	0.055	0.15	5	-0.2	12	17
BIRC5	0.076	0.074	0.18	165	-0.32	1	166
DES	-0.091	0.28	-10000	0	-0.58	114	114
Aurora C/Aurora B/INCENP	0.067	0.057	0.16	3	-0.14	4	7
Aurora B/TACC1	0.039	0.055	0.13	94	-0.13	13	107
Aurora B/PP2A	0.062	0.06	0.15	136	-0.11	16	152
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.012	0.017	0.11	11	-10000	0	11
mitotic metaphase/anaphase transition	-0.001	0.004	-10000	0	-10000	0	0
NDC80	-0.017	0.044	0.27	7	-0.22	3	10
Cul3 protein complex	0.041	0.052	-10000	0	-0.18	25	25
KIF2C	0.026	0.042	0.15	15	-0.29	2	17
PEBP1	0.025	0.006	-10000	0	-10000	0	0
KIF20A	0.078	0.072	0.18	171	-10000	0	171
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.059	0.06	0.15	130	-0.13	12	142
SEPT1	0.03	0.023	0.17	12	-10000	0	12
SMC2	0.026	0.006	-10000	0	-10000	0	0
SMC4	0.026	0.009	0.17	1	-10000	0	1
NSUN2/NPM1/Nucleolin	-0.005	0.17	0.29	11	-0.46	53	64
PSMA3	0.027	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	0.022	0.025	0.14	5	-0.14	3	8
AURKB	0.07	0.072	0.18	145	-10000	0	145
AURKC	0.026	0.024	0.17	3	-0.31	2	5
CDCA8	0.044	0.047	0.18	53	-10000	0	53
cytokinesis	0.032	0.066	0.22	13	-0.27	9	22
Aurora B/Septin1	0.06	0.11	0.26	27	-0.26	12	39
AURKA	0.034	0.033	0.17	26	-10000	0	26
INCENP	0.027	0.006	-10000	0	-10000	0	0
KLHL13	0.009	0.075	-10000	0	-0.31	26	26
BUB1	0.058	0.061	0.18	104	-10000	0	104
hSgo1/Aurora B/Survivin	0.1	0.12	0.27	136	-0.15	16	152
EVI5	0.027	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.059	0.067	0.22	20	-0.23	4	24
SGOL1	0.053	0.058	0.17	91	-10000	0	91
CENPA	0.03	0.069	0.21	12	-0.21	5	17
NCAPG	0.074	0.069	0.17	159	-10000	0	159
Aurora B/HC8 Proteasome	0.063	0.06	0.15	138	-0.11	15	153
NCAPD2	0.025	0.007	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.061	0.058	0.15	133	-0.11	12	145
RHOA	0.026	0.005	-10000	0	-10000	0	0
NCAPH	0.064	0.064	0.17	126	-10000	0	126
NPM1	0.002	0.1	0.19	2	-0.29	48	50
RASA1	0.025	0.016	-10000	0	-0.31	1	1
KLHL9	0.026	0.005	-10000	0	-10000	0	0
mitotic prometaphase	-0.001	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.062	0.06	0.15	138	-0.11	15	153
PPP1CC	0.026	0.006	-10000	0	-10000	0	0
Centraspindlin	0.057	0.074	0.24	29	-0.25	4	33
RhoA/GDP	0.019	0.004	-10000	0	-10000	0	0
NSUN2	0.003	0.1	0.19	3	-0.28	47	50
MYLK	-0.034	0.11	0.14	7	-0.24	100	107
KIF23	0.038	0.037	0.18	32	-10000	0	32
VIM	-0.019	0.03	0.26	2	-10000	0	2
RACGAP1	0.03	0.016	0.18	5	-10000	0	5
mitosis	0	0	-10000	0	-10000	0	0
NCL	0	0.1	-10000	0	-0.3	49	49
Chromosomal passenger complex	0.026	0.06	0.18	18	-0.2	7	25
Chromosomal passenger complex/EVI5	0.12	0.11	0.28	123	-0.16	12	135
TACC1	0.017	0.035	-10000	0	-0.31	5	5
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
CUL3	0.027	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.046	0.15	0.26	3	-0.43	56	59
CRKL	-0.047	0.15	0.2	2	-0.43	61	63
HRAS	-0.024	0.15	-10000	0	-0.41	58	58
mol:PIP3	-0.016	0.15	0.23	7	-0.38	61	68
SPRED1	0.023	0.034	-10000	0	-0.31	5	5
SPRED2	0.023	0.034	-10000	0	-0.31	5	5
GAB1	-0.047	0.16	-10000	0	-0.45	63	63
FOXO3	-0.018	0.15	0.26	6	-0.39	54	60
AKT1	-0.017	0.16	0.26	5	-0.42	56	61
BAD	-0.012	0.16	0.32	12	-0.39	54	66
megakaryocyte differentiation	-0.048	0.16	-10000	0	-0.44	64	64
GSK3B	-0.01	0.16	0.3	11	-0.39	54	65
RAF1	-0.02	0.12	0.23	6	-0.33	56	62
SHC1	0.026	0.006	-10000	0	-10000	0	0
STAT3	-0.048	0.16	-10000	0	-0.44	63	63
STAT1	-0.11	0.36	-10000	0	-1	65	65
HRAS/SPRED1	-0.007	0.13	-10000	0	-0.34	56	56
cell proliferation	-0.049	0.16	-10000	0	-0.44	64	64
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
TEC	0.026	0.005	-10000	0	-10000	0	0
RPS6KB1	-0.029	0.17	-10000	0	-0.46	57	57
HRAS/SPRED2	-0.007	0.13	-10000	0	-0.34	56	56
LYN/TEC/p62DOK	-0.007	0.16	-10000	0	-0.4	59	59
MAPK3	-0.006	0.1	0.26	16	-0.24	52	68
STAP1	-0.06	0.17	0.24	2	-0.48	63	65
GRAP2	0.016	0.06	0.17	2	-0.31	16	18
JAK2	-0.094	0.31	-10000	0	-0.86	64	64
STAT1 (dimer)	-0.11	0.35	-10000	0	-0.97	65	65
mol:Gleevec	0.001	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.011	0.18	-10000	0	-0.46	58	58
actin filament polymerization	-0.044	0.15	0.22	3	-0.42	62	65
LYN	0.023	0.01	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.082	0.24	-10000	0	-0.66	64	64
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
CBL/CRKL/GRB2	-0.018	0.15	-10000	0	-0.41	55	55
PI3K	-0.012	0.18	-10000	0	-0.46	55	55
PTEN	0.021	0.011	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.11	0.41	-10000	0	-1.2	58	58
MAPK8	-0.05	0.16	-10000	0	-0.45	64	64
STAT3 (dimer)	-0.047	0.16	-10000	0	-0.44	63	63
positive regulation of transcription	-0.002	0.088	0.24	16	-0.2	51	67
mol:GDP	-0.021	0.16	-10000	0	-0.42	58	58
PIK3C2B	-0.046	0.16	-10000	0	-0.45	61	61
CBL/CRKL	-0.03	0.15	-10000	0	-0.42	56	56
FER	-0.05	0.16	-10000	0	-0.45	65	65
SH2B3	-0.046	0.16	-10000	0	-0.44	63	63
PDPK1	-0.012	0.15	0.26	14	-0.37	53	67
SNAI2	-0.067	0.18	-10000	0	-0.49	64	64
positive regulation of cell proliferation	-0.079	0.28	-10000	0	-0.77	64	64
KITLG	0.001	0.081	-10000	0	-0.33	25	25
cell motility	-0.079	0.28	-10000	0	-0.77	64	64
PTPN6	0.026	0.012	-10000	0	-10000	0	0
EPOR	-0.005	0.12	-10000	0	-0.79	2	2
STAT5A (dimer)	-0.066	0.24	-10000	0	-0.65	63	63
SOCS1	0.026	0.02	0.17	3	-0.31	1	4
cell migration	0.059	0.16	0.45	64	-0.19	1	65
SOS1	0.026	0.005	-10000	0	-10000	0	0
EPO	-0.002	0.1	0.18	25	-0.32	42	67
VAV1	0.012	0.068	0.17	1	-0.31	21	22
GRB10	-0.046	0.15	-10000	0	-0.43	62	62
PTPN11	0.026	0.018	-10000	0	-0.3	1	1
SCF/KIT	-0.045	0.17	-10000	0	-0.47	63	63
GO:0007205	0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.012	0.11	0.26	14	-0.26	55	69
CBL	0.025	0.016	-10000	0	-0.31	1	1
KIT	-0.12	0.4	-10000	0	-1.2	57	57
MAP2K2	-0.012	0.11	0.26	14	-0.26	56	70
SHC/Grb2/SOS1	-0.006	0.16	-10000	0	-0.43	57	57
STAT5A	-0.068	0.24	-10000	0	-0.67	63	63
GRB2	0.026	0.005	-10000	0	-10000	0	0
response to radiation	-0.065	0.17	-10000	0	-0.48	65	65
SHC/GRAP2	0.03	0.045	0.14	2	-0.21	15	17
PTPRO	-0.048	0.16	-10000	0	-0.44	63	63
SH2B2	-0.045	0.16	0.22	3	-0.42	62	65
DOK1	0.026	0.016	-10000	0	-0.31	1	1
MATK	-0.06	0.17	0.19	1	-0.46	64	65
CREBBP	0.018	0.053	-10000	0	-0.12	57	57
BCL2	-0.1	0.36	-10000	0	-1.3	35	35

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.042	0.14	0.25	119	-10000	0	119
GNAI2	0.026	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.004	0.072	-10000	0	-0.18	67	67
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
RhoA/GTP	-0.043	0.14	-10000	0	-0.26	119	119
negative regulation of cAMP metabolic process	-0.044	0.14	-10000	0	-0.27	112	112
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNA12	0.024	0.008	-10000	0	-10000	0	0
S1PR5	-0.026	0.12	-10000	0	-0.31	78	78
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.045	0.14	-10000	0	-0.28	112	112
RhoA/GDP	0.019	0.004	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.023	0.028	0.17	1	-0.31	3	4

×

Ras signaling in the CD4+ TCR pathway

Figure S16. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.048	0.18	0.26	1	-0.38	90	91
MAP3K8	0.017	0.055	0.17	1	-0.31	13	14
FOS	-0.039	0.15	0.24	2	-0.37	54	56
PRKCA	0.005	0.07	-10000	0	-0.31	22	22
PTPN7	0.024	0.039	0.17	22	-10000	0	22
HRAS	0.028	0.017	0.17	6	-10000	0	6
PRKCB	-0.051	0.14	-10000	0	-0.31	107	107
NRAS	0.026	0.016	-10000	0	-0.32	1	1
RAS family/GTP	0.041	0.028	-10000	0	-10000	0	0
MAPK3	-0.01	0.093	-10000	0	-0.36	9	9
MAP2K1	-0.081	0.21	-10000	0	-0.43	105	105
ELK1	0.017	0.023	-10000	0	-10000	0	0
BRAF	-0.065	0.18	-10000	0	-0.41	90	90
mol:GTP	-0.001	0.002	-10000	0	-0.004	84	84
MAPK1	-0.015	0.11	-10000	0	-0.42	16	16
RAF1	-0.071	0.18	-10000	0	-0.4	101	101
KRAS	0.025	0.007	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.03	0.24	0.3	8	-0.57	54	62
HDAC7	0.025	0.013	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.024	0.3	-10000	0	-0.72	42	42
SMAD4	0.025	0.008	-10000	0	-10000	0	0
ID2	-0.02	0.26	0.34	5	-0.63	45	50
AP1	-0.003	0.1	0.19	3	-0.22	78	81
ABCG2	-0.031	0.27	0.34	5	-0.64	52	57
HIF1A	0.011	0.065	-10000	0	-0.21	5	5
TFF3	-0.002	0.27	0.36	7	-0.61	48	55
GATA2	0.023	0.018	0.18	1	-0.11	1	2
AKT1	0.008	0.078	-10000	0	-0.2	26	26
response to hypoxia	-0.01	0.073	-10000	0	-0.18	48	48
MCL1	-0.023	0.24	0.35	4	-0.6	45	49
NDRG1	-0.021	0.23	0.33	1	-0.6	38	39
SERPINE1	-0.016	0.25	0.33	2	-0.6	48	50
FECH	-0.019	0.25	0.34	6	-0.6	46	52
FURIN	-0.017	0.25	0.34	5	-0.59	48	53
NCOA2	-0.019	0.1	-10000	0	-0.31	53	53
EP300	-0.002	0.11	-10000	0	-0.31	37	37
HMOX1	-0.017	0.25	0.34	6	-0.6	48	54
BHLHE40	-0.019	0.25	0.35	5	-0.63	43	48
BHLHE41	-0.02	0.25	0.36	6	-0.61	46	52
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.061	0.096	-10000	0	-0.2	2	2
ENG	0.014	0.076	0.26	15	-10000	0	15
JUN	0.022	0.034	0.18	1	-0.31	4	5
RORA	-0.017	0.25	0.35	5	-0.61	45	50
ABCB1	0.004	0.16	-10000	0	-0.89	11	11
TFRC	-0.017	0.25	0.34	6	-0.61	44	50
CXCR4	-0.018	0.25	0.34	6	-0.6	48	54
TF	-0.041	0.28	0.34	6	-0.62	60	66
CITED2	-0.017	0.25	0.34	6	-0.61	44	50
HIF1A/ARNT	0.07	0.35	0.55	4	-0.75	32	36
LDHA	0.028	0.082	-10000	0	-0.79	2	2
ETS1	-0.02	0.25	0.35	4	-0.61	45	49
PGK1	-0.017	0.25	0.34	6	-0.6	47	53
NOS2	-0.021	0.27	0.34	6	-0.61	52	58
ITGB2	-0.016	0.25	0.34	5	-0.6	46	51
ALDOA	-0.018	0.25	0.35	5	-0.59	49	54
Cbp/p300/CITED2	-0.024	0.31	-10000	0	-0.75	50	50
FOS	-0.027	0.12	0.18	4	-0.31	78	82
HK2	-0.018	0.25	0.34	5	-0.6	47	52
SP1	0.029	0.016	-10000	0	-0.099	7	7
GCK	-0.035	0.3	-10000	0	-1.3	25	25
HK1	-0.018	0.25	0.34	5	-0.6	47	52
NPM1	-0.018	0.25	0.33	4	-0.6	47	51
EGLN1	-0.022	0.25	0.35	4	-0.61	44	48
CREB1	0.031	0.004	-10000	0	-10000	0	0
PGM1	-0.019	0.25	0.35	5	-0.59	48	53
SMAD3	0.027	0.002	-10000	0	-10000	0	0
EDN1	-0.052	0.29	0.35	1	-0.87	45	46
IGFBP1	-0.018	0.25	0.36	6	-0.61	43	49
VEGFA	-0.019	0.25	0.37	5	-0.63	44	49
HIF1A/JAB1	0.021	0.051	-10000	0	-0.19	2	2
CP	-0.03	0.28	0.35	7	-0.62	57	64
CXCL12	-0.02	0.26	0.34	6	-0.63	48	54
COPS5	0.018	0.019	-10000	0	-10000	0	0
SMAD3/SMAD4	0.037	0.012	-10000	0	-10000	0	0
BNIP3	-0.018	0.25	0.34	5	-0.59	48	53
EGLN3	-0.02	0.26	0.33	4	-0.62	47	51
CA9	-0.022	0.25	0.34	5	-0.61	44	49
TERT	-0.005	0.26	0.38	5	-0.59	50	55
ENO1	-0.018	0.25	0.34	6	-0.6	46	52
PFKL	-0.016	0.25	0.34	5	-0.6	47	52
NCOA1	0.024	0.012	-10000	0	-10000	0	0
ADM	-0.015	0.25	0.36	7	-0.6	46	53
ARNT	0.011	0.061	-10000	0	-0.19	3	3
HNF4A	0.024	0.045	0.18	26	-0.11	19	45
ADFP	-0.03	0.24	0.3	8	-0.57	54	62
SLC2A1	-0.013	0.24	0.37	5	-0.64	39	44
LEP	-0.018	0.24	0.33	3	-0.6	44	47
HIF1A/ARNT/Cbp/p300	0.016	0.31	-10000	0	-0.75	39	39
EPO	-0.073	0.32	0.44	1	-0.79	64	65
CREBBP	0.001	0.1	-10000	0	-0.31	33	33
HIF1A/ARNT/Cbp/p300/HDAC7	0.024	0.31	-10000	0	-0.75	38	38
PFKFB3	-0.021	0.26	0.34	5	-0.62	47	52
NT5E	-0.03	0.26	0.33	2	-0.63	49	51

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.03	0.027	0.17	16	-10000	0	16
EPHB2	0.025	0.033	0.17	3	-0.31	4	7
EFNB1	-0.011	0.026	-10000	0	-0.21	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.003	0.099	-10000	0	-0.16	112	112
Ephrin B2/EPHB1-2	-0.011	0.096	-10000	0	-0.16	137	137
neuron projection morphogenesis	-0.01	0.086	-10000	0	-0.15	114	114
Ephrin B1/EPHB1-2/Tiam1	-0.007	0.1	-10000	0	-0.17	124	124
DNM1	0.025	0.018	0.17	1	-0.31	1	2
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.006	0.054	0.2	1	-0.44	7	8
YES1	0.003	0.083	-10000	0	-0.68	7	7
Ephrin B1/EPHB1-2/NCK2	-0.006	0.096	-10000	0	-0.16	124	124
PI3K	0.028	0.069	-10000	0	-0.49	7	7
mol:GDP	-0.008	0.099	-10000	0	-0.17	124	124
ITGA2B	0.02	0.048	0.17	5	-0.31	9	14
endothelial cell proliferation	0.033	0.02	0.13	13	-10000	0	13
FYN	0	0.085	-10000	0	-0.68	7	7
MAP3K7	-0.004	0.053	-10000	0	-0.48	6	6
FGR	0.005	0.086	-10000	0	-0.65	8	8
TIAM1	0.023	0.03	-10000	0	-0.31	4	4
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
RGS3	0.025	0.007	-10000	0	-10000	0	0
cell adhesion	-0.013	0.09	-10000	0	-0.42	11	11
LYN	0.004	0.081	-10000	0	-0.66	7	7
Ephrin B1/EPHB1-2/Src Family Kinases	-0.004	0.083	-10000	0	-0.65	8	8
Ephrin B1/EPHB1-2	-0.003	0.062	-10000	0	-0.51	7	7
SRC	0.005	0.085	-10000	0	-0.65	8	8
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
EPHB1	-0.068	0.15	-10000	0	-0.31	137	137
EPHB4	0.024	0.008	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.034	0.02	0.13	13	-10000	0	13
alphaIIb/beta3 Integrin	-0.014	0.1	0.14	2	-0.21	101	103
BLK	-0.015	0.1	-10000	0	-0.68	8	8
HCK	0.003	0.087	-10000	0	-0.66	8	8
regulation of stress fiber formation	0.007	0.095	0.16	124	-10000	0	124
MAPK8	-0.007	0.062	0.21	6	-0.44	7	13
Ephrin B1/EPHB1-2/RGS3	-0.006	0.097	-10000	0	-0.16	127	127
endothelial cell migration	0.002	0.065	0.2	24	-0.38	7	31
NCK2	0.027	0.003	-10000	0	-10000	0	0
PTPN13	0.026	0.03	-10000	0	-0.42	2	2
regulation of focal adhesion formation	0.007	0.095	0.16	124	-10000	0	124
chemotaxis	0.007	0.095	0.16	127	-10000	0	127
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
Rac1/GTP	-0.004	0.092	-10000	0	-0.16	112	112
angiogenesis	-0.002	0.062	-10000	0	-0.51	7	7
LCK	0.006	0.086	-10000	0	-0.65	8	8

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.033	0.047	0.2	17	-0.27	5	22
NFATC2	0.016	0.16	-10000	0	-0.45	30	30
NFATC3	0.025	0.061	-10000	0	-0.22	11	11
CD40LG	-0.092	0.26	-10000	0	-0.77	43	43
ITCH	-0.018	0.082	-10000	0	-0.18	91	91
CBLB	-0.019	0.082	-10000	0	-0.18	95	95
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.074	0.26	-10000	0	-0.73	41	41
JUNB	0.024	0.053	0.17	12	-0.31	10	22
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.018	0.1	-10000	0	-0.22	100	100
T cell anergy	-0.058	0.15	0.29	3	-0.33	98	101
TLE4	-0.003	0.12	0.3	2	-0.37	21	23
Jun/NFAT1-c-4/p21SNFT	-0.011	0.24	-10000	0	-0.77	27	27
AP-1/NFAT1-c-4	-0.046	0.32	-10000	0	-0.86	39	39
IKZF1	0	0.11	0.29	1	-0.41	15	16
T-helper 2 cell differentiation	-0.15	0.26	-10000	0	-0.65	62	62
AP-1/NFAT1	-0.014	0.17	0.39	1	-0.36	53	54
CALM1	-0.003	0.07	-10000	0	-0.14	100	100
EGR2	-0.059	0.27	-10000	0	-1	26	26
EGR3	-0.067	0.29	-10000	0	-1.1	31	31
NFAT1/FOXP3	0.02	0.15	0.32	9	-0.37	23	32
EGR1	0.007	0.095	0.17	24	-0.31	36	60
JUN	0.013	0.042	0.18	1	-0.32	4	5
EGR4	0.062	0.067	0.17	128	-10000	0	128
mol:Ca2+	-0.022	0.056	-10000	0	-0.13	106	106
GBP3	-0.041	0.2	-10000	0	-0.56	54	54
FOSL1	-0.012	0.13	0.17	33	-0.31	70	103
NFAT1-c-4/MAF/IRF4	-0.006	0.23	-10000	0	-0.76	26	26
DGKA	-0.002	0.11	0.29	1	-0.36	16	17
CREM	0.026	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.019	0.23	-10000	0	-0.77	28	28
CTLA4	-0.003	0.12	0.33	5	-0.35	21	26
NFAT1-c-4 (dimer)/EGR1	-0.017	0.25	-10000	0	-0.81	29	29
NFAT1-c-4 (dimer)/EGR4	0.003	0.24	-10000	0	-0.75	27	27
FOS	-0.035	0.13	0.18	4	-0.32	78	82
IFNG	-0.05	0.19	-10000	0	-0.56	30	30
T cell activation	-0.032	0.16	-10000	0	-0.61	13	13
MAF	0.021	0.024	-10000	0	-0.31	2	2
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.019	0.16	0.63	24	-10000	0	24
TNF	-0.06	0.24	-10000	0	-0.74	34	34
FASLG	-0.12	0.39	-10000	0	-1.2	44	44
TBX21	0.03	0.051	0.19	18	-0.31	7	25
BATF3	0.032	0.031	0.17	22	-10000	0	22
PRKCQ	0.008	0.087	0.18	10	-0.29	34	44
PTPN1	-0.004	0.11	-10000	0	-0.34	21	21
NFAT1-c-4/ICER1	-0.013	0.22	-10000	0	-0.75	27	27
GATA3	-0.068	0.15	-10000	0	-0.31	139	139
T-helper 1 cell differentiation	-0.048	0.19	-10000	0	-0.56	30	30
IL2RA	-0.062	0.26	0.34	1	-0.69	45	46
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.003	0.11	-10000	0	-0.35	20	20
E2F1	0.034	0.028	0.18	18	-10000	0	18
PPARG	0.01	0.075	0.17	3	-0.31	25	28
SLC3A2	-0.003	0.11	0.32	1	-0.35	20	21
IRF4	0.022	0.07	0.17	24	-0.31	17	41
PTGS2	-0.11	0.28	-10000	0	-0.78	49	49
CSF2	-0.091	0.25	-10000	0	-0.75	40	40
JunB/Fra1/NFAT1-c-4	-0.022	0.24	-10000	0	-0.77	30	30
IL4	-0.16	0.27	-10000	0	-0.69	59	59
IL5	-0.091	0.24	-10000	0	-0.75	41	41
IL2	-0.033	0.16	-10000	0	-0.62	13	13
IL3	-0.018	0.12	-10000	0	-0.62	12	12
RNF128	-0.066	0.18	0.28	1	-0.41	103	104
NFATC1	-0.019	0.16	-10000	0	-0.63	24	24
CDK4	0.039	0.14	0.57	12	-10000	0	12
PTPRK	-0.004	0.11	-10000	0	-0.34	21	21
IL8	-0.095	0.26	-10000	0	-0.76	45	45
POU2F1	0.026	0.006	-10000	0	-10000	0	0

×

LPA receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.03	0.073	-10000	0	-0.19	44	44
NF kappa B1 p50/RelA/I kappa B alpha	-0.005	0.099	0.26	5	-0.26	23	28
AP1	-0.02	0.11	0.15	1	-0.19	128	129
mol:PIP3	-0.044	0.073	-10000	0	-0.23	43	43
AKT1	0.006	0.092	0.33	17	-0.24	7	24
PTK2B	-0.053	0.12	0.24	2	-0.29	68	70
RHOA	0.006	0.043	0.2	5	-0.26	4	9
PIK3CB	0.025	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.085	0.22	23	-0.26	15	38
MAGI3	0.027	0.004	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
apoptosis	-0.024	0.091	-10000	0	-0.21	88	88
HRAS/GDP	0.021	0.012	0.12	6	-10000	0	6
positive regulation of microtubule depolymerization	-0.044	0.11	0.25	12	-0.28	54	66
NF kappa B1 p50/RelA	-0.012	0.094	-10000	0	-0.25	37	37
endothelial cell migration	-0.004	0.075	-10000	0	-0.25	34	34
ADCY4	-0.036	0.15	0.23	3	-0.42	52	55
ADCY5	-0.057	0.19	0.23	2	-0.5	64	66
ADCY6	-0.034	0.15	0.23	4	-0.41	52	56
ADCY7	-0.034	0.15	0.23	4	-0.41	53	57
ADCY1	-0.035	0.14	0.23	2	-0.42	49	51
ADCY2	-0.041	0.16	0.23	4	-0.43	57	61
ADCY3	-0.035	0.15	0.23	4	-0.41	53	57
ADCY8	-0.033	0.13	-10000	0	-0.4	47	47
ADCY9	-0.035	0.15	0.23	3	-0.41	53	56
GSK3B	-0.046	0.12	0.25	11	-0.29	58	69
arachidonic acid secretion	-0.042	0.15	-10000	0	-0.41	55	55
GNG2	0.022	0.037	-10000	0	-0.31	6	6
TRIP6	0.014	0.034	0.19	1	-0.26	6	7
GNAO1	-0.026	0.1	-10000	0	-0.25	72	72
HRAS	0.028	0.017	0.17	6	-10000	0	6
NFKBIA	-0.02	0.11	0.34	10	-0.27	29	39
GAB1	0.026	0.016	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.001	0.19	-10000	0	-0.81	25	25
JUN	0.024	0.031	0.17	1	-0.31	4	5
LPA/LPA2/NHERF2	0.035	0.022	0.13	5	-0.16	2	7
TIAM1	-0.017	0.22	-10000	0	-0.95	25	25
PIK3R1	0.021	0.031	-10000	0	-0.31	4	4
mol:IP3	-0.017	0.079	0.19	22	-0.27	14	36
PLCB3	0.015	0.037	0.18	20	-10000	0	20
FOS	-0.026	0.12	0.17	4	-0.31	78	82
positive regulation of mitosis	-0.042	0.15	-10000	0	-0.41	55	55
LPA/LPA1-2-3	0.008	0.098	-10000	0	-0.19	90	90
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.022	0.011	-10000	0	-10000	0	0
stress fiber formation	-0.028	0.11	0.29	9	-0.29	45	54
GNAZ	-0.017	0.091	-10000	0	-0.24	62	62
EGFR/PI3K-beta/Gab1	-0.016	0.089	-10000	0	-0.2	75	75
positive regulation of dendritic cell cytokine production	0.007	0.097	-10000	0	-0.18	90	90
LPA/LPA2/MAGI-3	0.035	0.019	-10000	0	-0.12	4	4
ARHGEF1	0.013	0.079	0.2	47	-0.18	28	75
GNAI2	-0.003	0.061	-10000	0	-0.2	40	40
GNAI3	-0.004	0.063	-10000	0	-0.2	41	41
GNAI1	-0.002	0.061	0.19	1	-0.21	35	36
LPA/LPA3	-0.01	0.08	0.12	6	-0.2	69	75
LPA/LPA2	0.019	0.018	-10000	0	-0.14	4	4
LPA/LPA1	0.001	0.077	-10000	0	-0.23	44	44
HB-EGF/EGFR	-0.028	0.068	0.2	6	-0.2	43	49
HBEGF	-0.032	0.052	0.26	10	-0.22	7	17
mol:DAG	-0.017	0.079	0.19	22	-0.27	14	36
cAMP biosynthetic process	-0.035	0.17	0.31	14	-0.42	56	70
NFKB1	0.027	0.004	-10000	0	-10000	0	0
SRC	0.026	0.006	-10000	0	-10000	0	0
GNB1	0.026	0.005	-10000	0	-10000	0	0
LYN	-0.008	0.12	0.31	21	-0.29	23	44
GNAQ	-0.01	0.065	-10000	0	-0.18	59	59
LPAR2	0.026	0.015	-10000	0	-0.31	1	1
LPAR3	-0.016	0.12	0.17	7	-0.31	65	72
LPAR1	-0.003	0.099	-10000	0	-0.32	43	43
IL8	-0.054	0.18	0.46	6	-0.42	73	79
PTK2	-0.017	0.068	0.18	6	-0.21	20	26
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
CASP3	-0.024	0.091	-10000	0	-0.21	88	88
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
PLCG1	-0.019	0.074	0.16	1	-0.21	56	57
PLD2	-0.019	0.082	0.19	13	-0.21	39	52
G12/G13	0.032	0.063	-10000	0	-0.18	35	35
PI3K-beta	0.005	0.054	-10000	0	-0.26	9	9
cell migration	-0.005	0.066	-10000	0	-0.25	23	23
SLC9A3R2	0.027	0.016	0.17	5	-10000	0	5
PXN	-0.029	0.12	0.29	9	-0.3	45	54
HRAS/GTP	-0.045	0.15	-10000	0	-0.42	55	55
RAC1	0.025	0.008	-10000	0	-10000	0	0
MMP9	0.1	0.085	0.17	258	-0.31	5	263
PRKCE	0.026	0.006	-10000	0	-10000	0	0
PRKCD	-0.016	0.089	0.23	26	-0.27	14	40
Gi(beta/gamma)	-0.035	0.14	-10000	0	-0.39	54	54
mol:LPA	0	0.016	-10000	0	-0.15	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.012	0.094	-10000	0	-0.3	22	22
MAPKKK cascade	-0.042	0.15	-10000	0	-0.41	55	55
contractile ring contraction involved in cytokinesis	0.007	0.045	0.22	5	-0.25	4	9
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.011	0.066	-10000	0	-0.18	61	61
GNA15	-0.016	0.076	-10000	0	-0.2	70	70
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
MAPT	-0.045	0.12	0.25	12	-0.28	54	66
GNA11	-0.015	0.076	-10000	0	-0.2	66	66
Rac1/GTP	0.001	0.2	-10000	0	-0.86	25	25
MMP2	-0.004	0.076	-10000	0	-0.25	34	34

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.029	0.12	-10000	0	-0.31	81	81
GNB1/GNG2	-0.008	0.12	-10000	0	-0.3	36	36
mol:DAG	-0.019	0.1	0.19	14	-0.28	36	50
PLCG1	-0.02	0.11	0.19	14	-0.28	36	50
YES1	-0.028	0.093	-10000	0	-0.23	67	67
FZD3	0.02	0.012	-10000	0	-10000	0	0
FZD6	0.021	0.011	-10000	0	-10000	0	0
G protein	-0.004	0.12	0.28	3	-0.29	36	39
MAP3K7	-0.04	0.1	0.19	17	-0.27	46	63
mol:Ca2+	-0.018	0.1	0.19	14	-0.27	36	50
mol:IP3	-0.019	0.1	0.19	14	-0.28	36	50
NLK	0.003	0.08	-10000	0	-0.78	5	5
GNB1	0.027	0.004	-10000	0	-10000	0	0
CAMK2A	-0.038	0.12	0.21	20	-0.27	56	76
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.019	0.1	-10000	0	-0.24	71	71
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
GNAS	-0.03	0.094	-10000	0	-0.23	71	71
GO:0007205	-0.023	0.1	0.21	18	-0.27	37	55
WNT6	-0.03	0.13	0.17	7	-0.31	87	94
WNT4	0.023	0.034	-10000	0	-0.31	5	5
NFAT1/CK1 alpha	-0.033	0.12	-10000	0	-0.29	44	44
GNG2	0.023	0.037	-10000	0	-0.31	6	6
WNT5A	0.015	0.074	0.17	12	-0.31	22	34
WNT11	0.027	0.054	0.17	23	-0.31	8	31
CDC42	-0.027	0.092	0.17	1	-0.29	31	32

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.08	0.14	4	-0.23	44	48
PDGFRB	0.025	0.014	0.17	2	-10000	0	2
SPHK1	-0.007	0.084	-10000	0	-0.63	7	7
mol:S1P	-0.01	0.08	0.29	1	-0.52	7	8
S1P1/S1P/Gi	-0.1	0.2	0.22	1	-0.43	116	117
GNAO1	-0.03	0.12	-10000	0	-0.31	71	71
PDGFB-D/PDGFRB/PLCgamma1	-0.077	0.19	0.24	4	-0.38	109	113
PLCG1	-0.096	0.19	0.21	1	-0.4	112	113
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.014	0.17	2	-10000	0	2
GNAI2	0.018	0.021	-10000	0	-10000	0	0
GNAI3	0.018	0.02	-10000	0	-10000	0	0
GNAI1	0.015	0.033	0.17	1	-0.32	3	4
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.027	0.054	-10000	0	-0.19	44	44
S1P1/S1P	-0.027	0.091	0.18	7	-0.31	21	28
negative regulation of cAMP metabolic process	-0.098	0.2	0.21	1	-0.41	116	117
MAPK3	-0.13	0.25	0.24	2	-0.55	115	117
calcium-dependent phospholipase C activity	-0.002	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.004	-10000	0	-10000	0	0
KDR	0.007	0.07	-10000	0	-0.31	22	22
PLCB2	-0.019	0.09	0.25	7	-0.29	20	27
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.023	0.079	-10000	0	-0.27	21	21
receptor internalization	-0.027	0.084	0.16	5	-0.29	21	26
PTGS2	-0.19	0.39	0.37	1	-0.94	96	97
Rac1/GTP	-0.021	0.077	-10000	0	-0.28	20	20
RHOA	0.026	0.005	-10000	0	-10000	0	0
VEGFA	0.006	0.078	0.17	5	-0.31	26	31
negative regulation of T cell proliferation	-0.098	0.2	0.21	1	-0.41	116	117
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.01	0.095	-10000	0	-0.32	42	42
MAPK1	-0.13	0.26	0.21	1	-0.56	115	116
S1P1/S1P/PDGFB-D/PDGFRB	-0.022	0.1	0.22	8	-0.27	35	43
ABCC1	0.019	0.018	-10000	0	-10000	0	0

×

IL6-mediated signaling events

Figure S23. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S23. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0.15	0.43	2	-0.52	7	9
CRP	0.001	0.15	0.53	3	-0.54	7	10
cell cycle arrest	-0.005	0.16	0.38	1	-0.55	12	13
TIMP1	0.003	0.17	-10000	0	-0.82	9	9
IL6ST	-0.033	0.12	-10000	0	-0.31	81	81
Rac1/GDP	-0.053	0.17	-10000	0	-0.36	90	90
AP1	0.017	0.13	-10000	0	-0.52	13	13
GAB2	0.026	0.006	-10000	0	-10000	0	0
TNFSF11	-0.005	0.16	0.47	1	-0.64	11	12
HSP90B1	0.027	0.079	-10000	0	-0.58	5	5
GAB1	0.026	0.016	-10000	0	-0.31	1	1
MAPK14	-0.11	0.24	0.23	2	-0.55	93	95
AKT1	0.024	0.065	0.25	2	-0.48	4	6
FOXO1	0.018	0.062	0.24	2	-0.45	4	6
MAP2K6	-0.086	0.2	-10000	0	-0.44	98	98
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.043	0.16	0.3	3	-0.35	76	79
MITF	-0.064	0.16	0.16	1	-0.36	92	93
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.027	0.003	-10000	0	-10000	0	0
A2M	-0.058	0.3	-10000	0	-1.1	35	35
CEBPB	0.03	0.006	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.002	0.1	-10000	0	-0.44	14	14
STAT3	-0.01	0.16	-10000	0	-0.56	14	14
STAT1	0.015	0.074	-10000	0	-0.87	3	3
CEBPD	0.016	0.16	0.41	1	-0.52	9	10
PIK3CA	0.024	0.027	-10000	0	-0.31	3	3
PI3K	0.032	0.035	-10000	0	-0.24	6	6
JUN	0.024	0.031	0.17	1	-0.31	4	5
PIAS3/MITF	-0.055	0.17	0.22	3	-0.36	90	93
MAPK11	-0.11	0.24	0.23	2	-0.56	94	96
STAT3 (dimer)/FOXO1	0.004	0.13	0.35	2	-0.44	10	12
GRB2/SOS1/GAB family	-0.032	0.16	-10000	0	-0.32	85	85
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.06	0.16	0.16	4	-0.3	121	125
GRB2	0.026	0.005	-10000	0	-10000	0	0
JAK2	0.026	0.016	-10000	0	-0.31	1	1
LBP	0.01	0.14	0.46	1	-0.5	6	7
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
JAK1	0.021	0.021	-10000	0	-10000	0	0
MYC	0.03	0.16	0.47	7	-0.5	9	16
FGG	-0.006	0.14	-10000	0	-0.54	7	7
macrophage differentiation	-0.005	0.16	0.38	1	-0.55	12	13
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.01	0.15	-10000	0	-0.23	123	123
JUNB	-0.015	0.19	0.51	1	-0.87	13	14
FOS	-0.026	0.12	0.17	4	-0.31	78	82
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.061	0.17	-10000	0	-0.38	94	94
STAT1/PIAS1	-0.025	0.15	0.28	2	-0.3	74	76
GRB2/SOS1/GAB family/SHP2/PI3K	0.026	0.068	-10000	0	-0.45	5	5
STAT3 (dimer)	-0.006	0.16	-10000	0	-0.57	12	12
PRKCD	-0.022	0.17	0.31	19	-0.43	34	53
IL6R	-0.004	0.089	-10000	0	-0.31	37	37
SOCS3	-0.16	0.38	0.42	1	-1.1	61	62
gp130 (dimer)/JAK1/JAK1/LMO4	0.005	0.095	-10000	0	-0.18	83	83
Rac1/GTP	-0.049	0.17	-10000	0	-0.36	85	85
HCK	0.024	0.031	0.17	1	-0.31	4	5
MAPKKK cascade	0.011	0.11	-10000	0	-0.54	12	12
bone resorption	-0.003	0.15	0.47	1	-0.6	11	12
IRF1	-0.002	0.15	0.45	1	-0.54	7	8
mol:GDP	-0.066	0.17	-10000	0	-0.37	95	95
SOS1	0.026	0.005	-10000	0	-10000	0	0
VAV1	-0.067	0.17	-10000	0	-0.37	95	95
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.27	0.32	1	-0.58	99	100
PTPN11	0.008	0.086	-10000	0	-0.68	7	7
IL6/IL6RA	-0.016	0.13	0.15	43	-0.23	114	157
gp130 (dimer)/TYK2/TYK2/LMO4	0.006	0.091	-10000	0	-0.18	82	82
gp130 (dimer)/JAK2/JAK2/LMO4	0.006	0.091	-10000	0	-0.18	82	82
IL6	-0.022	0.15	0.18	46	-0.32	90	136
PIAS3	0.026	0.005	-10000	0	-10000	0	0
PTPRE	0.016	0.035	0.16	1	-0.31	4	5
PIAS1	0.026	0.015	-10000	0	-0.31	1	1
RAC1	0.025	0.008	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.058	0.15	0.16	5	-0.28	134	139
LMO4	0.022	0.03	-10000	0	-0.38	1	1
STAT3 (dimer)/PIAS3	-0.01	0.16	-10000	0	-0.55	14	14
MCL1	0.03	0.079	0.54	1	-0.79	1	2

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.006	0.12	-10000	0	-0.51	21	21
IHH	0.036	0.075	0.22	29	-0.21	21	50
SHH Np/Cholesterol/GAS1	-0.023	0.082	0.16	3	-0.18	98	101
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.024	0.081	0.18	98	-0.12	1	99
SMO/beta Arrestin2	0.014	0.098	-10000	0	-0.33	22	22
SMO	-0.002	0.089	-10000	0	-0.34	23	23
AKT1	0	0.094	-10000	0	-0.39	13	13
ARRB2	0.025	0.008	-10000	0	-10000	0	0
BOC	0.018	0.052	-10000	0	-0.31	12	12
ADRBK1	0.026	0.006	-10000	0	-10000	0	0
heart looping	-0.001	0.088	-10000	0	-0.34	23	23
STIL	-0.011	0.096	0.19	28	-0.28	23	51
DHH N/PTCH2	0.037	0.035	-10000	0	-0.21	8	8
DHH N/PTCH1	0.02	0.079	-10000	0	-0.24	35	35
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
DHH	0.024	0.039	0.17	3	-0.31	6	9
PTHLH	-0.007	0.15	-10000	0	-0.65	21	21
determination of left/right symmetry	-0.001	0.088	-10000	0	-0.34	23	23
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
skeletal system development	-0.006	0.15	-10000	0	-0.65	21	21
IHH N/Hhip	0.015	0.11	0.2	2	-0.27	55	57
DHH N/Hhip	0.014	0.079	-10000	0	-0.21	51	51
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.001	0.088	-10000	0	-0.34	23	23
pancreas development	-0.003	0.097	0.17	3	-0.31	45	48
HHAT	0.021	0.04	-10000	0	-0.31	7	7
PI3K	0.031	0.034	-10000	0	-0.24	6	6
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.007	0.1	0.17	1	-0.31	48	49
somite specification	-0.001	0.088	-10000	0	-0.34	23	23
SHH Np/Cholesterol/PTCH1	-0.009	0.089	0.18	3	-0.28	26	29
SHH Np/Cholesterol/PTCH2	-0.009	0.071	0.15	9	-0.16	71	80
SHH Np/Cholesterol/Megalin	-0.02	0.082	0.14	11	-0.17	99	110
SHH	-0.041	0.078	0.26	5	-0.22	69	74
catabolic process	0.007	0.081	-10000	0	-0.27	35	35
SMO/Vitamin D3	-0.012	0.096	0.22	4	-0.3	27	31
SHH Np/Cholesterol/Hhip	-0.022	0.089	0.16	6	-0.19	92	98
LRP2	0.001	0.093	0.17	9	-0.31	39	48
receptor-mediated endocytosis	-0.027	0.1	-10000	0	-0.32	30	30
SHH Np/Cholesterol/BOC	-0.013	0.072	0.18	4	-0.16	78	82
SHH Np/Cholesterol/CDO	-0.009	0.067	0.16	5	-0.16	70	75
mesenchymal cell differentiation	0.023	0.087	0.19	92	-0.14	3	95
mol:Vitamin D3	-0.004	0.1	0.19	30	-0.29	24	54
IHH N/PTCH2	0.037	0.066	0.2	3	-0.21	23	26
CDON	0.026	0.02	0.17	3	-0.31	1	4
IHH N/PTCH1	0.022	0.09	0.25	1	-0.27	35	36
Megalin/LRPAP1	0.019	0.071	-10000	0	-0.21	40	40
PTCH2	0.027	0.025	0.17	4	-0.31	2	6
SHH Np/Cholesterol	-0.017	0.061	-10000	0	-0.16	72	72
PTCH1	0.007	0.082	-10000	0	-0.27	35	35
HHIP	-0.003	0.097	0.17	3	-0.31	45	48

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.038	0.009	-10000	0	-10000	0	0
Necdin/E2F1	0.039	0.03	0.14	15	-0.24	3	18
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.043	0.08	-10000	0	-0.16	59	59
NGF (dimer)/p75(NTR)/BEX1	-0.038	0.13	-10000	0	-0.21	170	170
NT-4/5 (dimer)/p75(NTR)	-0.032	0.13	-10000	0	-0.26	116	116
IKBKB	0.021	0.011	-10000	0	-10000	0	0
AKT1	-0.024	0.069	0.17	27	-0.29	5	32
IKBKG	0.027	0.002	-10000	0	-10000	0	0
BDNF	-0.039	0.13	-10000	0	-0.31	96	96
MGDIs/NGR/p75(NTR)/LINGO1	0.041	0.073	-10000	0	-0.18	41	41
FURIN	0.027	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.008	0.11	-10000	0	-0.21	110	110
LINGO1	0.042	0.045	0.17	51	-10000	0	51
Sortilin/TRAF6/NRIF	0.033	0.014	-10000	0	-10000	0	0
proBDNF (dimer)	-0.039	0.13	-10000	0	-0.31	96	96
NTRK1	0.01	0.078	0.17	8	-0.31	26	34
RTN4R	0.026	0.005	-10000	0	-10000	0	0
neuron apoptosis	-0.042	0.13	0.35	6	-0.36	34	40
IRAK1	0.027	0.002	-10000	0	-10000	0	0
SHC1	-0.032	0.055	-10000	0	-0.19	54	54
ARHGDIA	0.026	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.072	0.025	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.037	0.082	-10000	0	-0.17	60	60
MAGEH1	0.028	0.023	0.17	7	-0.31	1	8
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.036	0.081	-10000	0	-0.18	59	59
Mammalian IAPs/DIABLO	0.063	0.026	-10000	0	-0.17	2	2
proNGF (dimer)	0.013	0.068	0.17	2	-0.31	21	23
MAGED1	0.027	0.007	0.17	1	-10000	0	1
APP	0.025	0.022	-10000	0	-0.31	2	2
NT-4/5 (dimer)	-0.048	0.14	-10000	0	-0.31	109	109
ZNF274	0.027	0.003	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.011	0.064	-10000	0	-0.16	59	59
NGF	0.013	0.069	0.17	2	-0.31	21	23
cell cycle arrest	0	0.084	0.26	20	-0.26	2	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.003	0.065	0.15	7	-0.19	46	53
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.01	0.12	-10000	0	-0.22	113	113
NCSTN	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0.022	0.079	-10000	0	-0.18	60	60
PSENEN	0.027	0.003	-10000	0	-10000	0	0
mol:ceramide	-0.024	0.054	0.18	10	-0.17	42	52
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.003	0.055	-10000	0	-0.29	3	3
p75(NTR)/beta APP	0.017	0.071	-10000	0	-0.22	40	40
BEX1	-0.073	0.16	0.17	5	-0.31	149	154
mol:GDP	-0.03	0.057	-10000	0	-0.18	60	60
NGF (dimer)	0.05	0.088	0.24	2	-0.17	51	53
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.055	0.074	0.19	1	-0.17	40	41
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
RAC1/GTP	0.019	0.065	-10000	0	-0.16	56	56
MYD88	0.026	0.005	-10000	0	-10000	0	0
CHUK	0.025	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.022	0.08	-10000	0	-0.19	60	60
RHOB	0.021	0.042	-10000	0	-0.31	8	8
RHOA	0.026	0.005	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.041	0.021	0.14	16	-10000	0	16
NT3 (dimer)	-0.005	0.095	-10000	0	-0.31	44	44
TP53	-0.039	0.086	0.22	16	-0.27	20	36
PRDM4	-0.031	0.056	0.18	7	-0.17	56	63
BDNF (dimer)	-0.001	0.14	0.24	7	-0.19	146	153
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
SORT1	0.026	0.005	-10000	0	-10000	0	0
activation of caspase activity	0.038	0.077	-10000	0	-0.16	59	59
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.037	0.078	-10000	0	-0.17	57	57
RHOC	0.027	0.004	-10000	0	-10000	0	0
XIAP	0.027	0.001	-10000	0	-10000	0	0
MAPK10	-0.037	0.12	0.41	7	-0.3	46	53
DIABLO	0.026	0.006	-10000	0	-10000	0	0
SMPD2	-0.024	0.055	0.18	10	-0.17	42	52
APH1B	0.027	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.006	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.023	0.08	-10000	0	-0.19	60	60
PSEN1	0.026	0.004	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.01	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.004	0.1	-10000	0	-0.24	70	70
MAPK8	-0.041	0.12	0.44	6	-0.3	51	57
MAPK9	-0.037	0.11	0.4	7	-0.29	46	53
APAF1	0.026	0.006	-10000	0	-10000	0	0
NTF3	-0.005	0.095	-10000	0	-0.31	44	44
NTF4	-0.048	0.14	-10000	0	-0.31	109	109
NDN	0.024	0.026	-10000	0	-0.31	3	3
RAC1/GDP	0.018	0.006	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.035	0.079	-10000	0	-0.16	58	58
p75 CTF/Sortilin/TRAF6/NRIF	0.062	0.032	-10000	0	-0.17	6	6
RhoA-B-C/GTP	0.021	0.079	-10000	0	-0.18	60	60
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.016	0.11	-10000	0	-0.18	109	109
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.006	0.11	-10000	0	-0.19	110	110
PRKACB	0.026	0.005	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.012	0.1	-10000	0	-0.22	95	95
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.025	0.025	0.17	3	-0.31	2	5
BIRC2	0.026	0.006	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.003	0.08	0.26	7	-0.2	30	37
BAD	-0.035	0.13	0.38	14	-0.3	48	62
RIPK2	0.021	0.011	-10000	0	-10000	0	0
NGFR	-0.001	0.093	-10000	0	-0.31	41	41
CYCS	-0.029	0.056	0.2	8	-0.26	3	11
ADAM17	0.022	0.037	-10000	0	-0.31	6	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.032	0.076	-10000	0	-0.17	48	48
BCL2L11	-0.037	0.13	0.31	17	-0.3	48	65
BDNF (dimer)/p75(NTR)	-0.027	0.12	-10000	0	-0.25	111	111
PI3K	0.029	0.08	-10000	0	-0.17	59	59
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.036	0.079	-10000	0	-0.17	58	58
NDNL2	0.026	0.005	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
PRKCI	0.025	0.01	0.17	1	-10000	0	1
NGF (dimer)/p75(NTR)	0.007	0.086	0.14	2	-0.22	60	62
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.037	0.08	-10000	0	-0.17	60	60
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.027	0.004	-10000	0	-10000	0	0
PLG	0.029	0.033	0.17	23	-10000	0	23
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.039	0.11	0.15	3	-0.21	119	122
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
NGFRAP1	0.027	0.001	-10000	0	-10000	0	0
CASP3	-0.032	0.12	0.33	16	-0.29	48	64
E2F1	0.032	0.028	0.17	18	-10000	0	18
CASP9	0.027	0.003	-10000	0	-10000	0	0
IKK complex	0.026	0.088	-10000	0	-0.24	23	23
NGF (dimer)/TRKA	0.016	0.078	0.14	10	-0.22	46	56
MMP7	0.017	0.1	0.17	50	-0.31	35	85
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.046	0.079	-10000	0	-0.16	56	56
MMP3	0.003	0.1	0.17	31	-0.31	45	76
APAF-1/Caspase 9	-0.04	0.043	-10000	0	-0.23	5	5

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.01	0.08	0.2	9	-0.16	75	84
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.09	0.35	1	-0.28	17	18
alphaV/beta3 Integrin/Osteopontin/Src	0.051	0.046	0.15	56	-0.19	4	60
AP1	-0.019	0.13	0.23	1	-0.32	39	40
ILK	-0.021	0.078	0.2	9	-0.2	21	30
bone resorption	-0.028	0.094	0.17	2	-0.28	41	43
PTK2B	0.019	0.012	-10000	0	-10000	0	0
PYK2/p130Cas	0.021	0.094	0.26	2	-0.17	47	49
ITGAV	0.026	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.013	0.079	-10000	0	-0.23	45	45
alphaV/beta3 Integrin/Osteopontin	0.021	0.1	-10000	0	-0.18	89	89
MAP3K1	-0.019	0.072	0.18	6	-0.17	73	79
JUN	0.024	0.031	0.17	1	-0.31	4	5
MAPK3	-0.037	0.075	0.22	11	-0.26	14	25
MAPK1	-0.038	0.075	0.22	10	-0.24	17	27
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.037	0.07	0.18	8	-0.24	23	31
ITGB3	-0.036	0.13	-10000	0	-0.31	92	92
NFKBIA	-0.03	0.082	0.2	7	-0.29	18	25
FOS	-0.026	0.12	0.17	4	-0.31	78	82
CD44	0.02	0.045	-10000	0	-0.31	9	9
CHUK	0.025	0.007	-10000	0	-10000	0	0
PLAU	-0.047	0.18	0.43	2	-1.1	12	14
NF kappa B1 p50/RelA	0.007	0.095	0.31	1	-0.36	12	13
BCAR1	0.022	0.011	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.008	0.099	-10000	0	-0.21	92	92
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.022	0.08	0.2	8	-0.18	83	91
VAV3	-0.051	0.093	0.22	10	-0.28	37	47
MAP3K14	-0.02	0.078	0.2	9	-0.17	79	88
ROCK2	-0.001	0.093	-10000	0	-0.31	41	41
SPP1	0.045	0.06	0.18	69	-0.31	3	72
RAC1	0.025	0.008	-10000	0	-10000	0	0
Rac1/GTP	-0.031	0.089	0.19	7	-0.26	33	40
MMP2	-0.054	0.096	-10000	0	-0.32	33	33

×

EPO signaling pathway

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
BCL2L1	0.026	0.12	0.39	6	-0.46	5	11
CRKL	-0.004	0.079	0.18	50	-0.2	5	55
mol:DAG	0.005	0.077	0.17	2	-0.23	37	39
HRAS	-0.005	0.088	0.3	18	-0.21	3	21
MAPK8	-0.002	0.084	0.18	67	-0.16	43	110
RAP1A	-0.004	0.08	0.18	50	-0.21	5	55
GAB1	-0.004	0.08	0.18	51	-0.21	6	57
MAPK14	0.002	0.083	0.18	70	-0.16	35	105
EPO	0.005	0.1	0.19	25	-0.31	40	65
PLCG1	0.005	0.079	0.17	2	-0.24	37	39
EPOR/TRPC2/IP3 Receptors	0.027	0.032	0.19	10	-10000	0	10
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.012	0.099	0.21	2	-0.19	85	87
GAB1/SHC/GRB2/SOS1	0.034	0.071	0.27	2	-0.2	6	8
EPO/EPOR (dimer)	0.023	0.082	0.16	33	-0.22	41	74
IRS2	-0.009	0.073	0.17	39	-0.2	6	45
STAT1	0.007	0.088	0.21	4	-0.24	44	48
STAT5B	0.005	0.082	0.18	2	-0.24	37	39
cell proliferation	0.006	0.1	0.21	79	-0.17	12	91
GAB1/SHIP/PIK3R1/SHP2/SHC	0.01	0.077	-10000	0	-0.25	17	17
TEC	-0.004	0.079	0.18	49	-0.21	5	54
SOCS3	-0.012	0.11	0.17	6	-0.31	58	64
STAT1 (dimer)	0.008	0.087	0.21	4	-0.24	44	48
JAK2	0.023	0.025	-10000	0	-0.31	1	1
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
EPO/EPOR (dimer)/JAK2	0.048	0.079	0.24	2	-0.16	41	43
EPO/EPOR	0.023	0.082	0.16	33	-0.22	41	74
LYN	0.022	0.013	-10000	0	-10000	0	0
TEC/VAV2	0.016	0.068	0.23	7	-0.21	5	12
elevation of cytosolic calcium ion concentration	0.027	0.032	0.19	10	-10000	0	10
SHC1	0.026	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.032	0.072	0.18	3	-0.18	38	41
mol:IP3	0.005	0.077	0.17	2	-0.23	37	39
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.016	0.086	0.32	3	-0.24	18	21
SH2B3	0.022	0.02	-10000	0	-10000	0	0
NFKB1	0.002	0.083	0.18	71	-0.16	34	105
EPO/EPOR (dimer)/JAK2/SOCS3	-0.019	0.08	-10000	0	-0.19	79	79
PTPN6	0.009	0.073	0.17	51	-0.16	40	91
TEC/VAV2/GRB2	0.029	0.069	0.27	3	-0.2	5	8
EPOR	0.027	0.032	0.19	10	-10000	0	10
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
mol:GDP	0.033	0.071	0.27	2	-0.2	6	8
SOS1	0.026	0.005	-10000	0	-10000	0	0
PLCG2	0.021	0.026	0.17	2	-0.31	2	4
CRKL/CBL/C3G	0.027	0.069	0.25	4	-0.22	5	9
VAV2	-0.008	0.072	0.17	43	-0.21	5	48
CBL	-0.008	0.075	0.18	41	-0.22	6	47
SHC/Grb2/SOS1	0.021	0.062	-10000	0	-0.2	5	5
STAT5A	0.005	0.082	0.18	2	-0.24	37	39
GRB2	0.026	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.018	0.092	-10000	0	-0.3	17	17
LYN/PLCgamma2	0.028	0.026	0.14	2	-0.22	2	4
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
BTK	-0.003	0.083	0.18	52	-0.21	8	60
BCL2	0.002	0.18	0.4	6	-0.66	25	31

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.028	0.017	0.17	6	-10000	0	6
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
EGF/EGFR	0.005	0.11	0.2	2	-0.19	95	97
EGF/EGFR dimer/SHC/GRB2/SOS1	0.045	0.083	-10000	0	-0.17	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.007	0.1	-10000	0	-0.31	50	50
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.023	0.084	0.17	40	-0.31	23	63
EGF/EGFR dimer/SHC	0.027	0.083	-10000	0	-0.19	52	52
mol:GDP	0.04	0.079	-10000	0	-0.17	49	49
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.013	0.076	0.17	10	-0.31	24	34
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
HRAS/GTP	0.024	0.067	-10000	0	-0.16	49	49
SHC1	0.026	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.038	0.077	-10000	0	-0.16	49	49
FRAP1	-0.029	0.049	0.13	7	-0.16	49	56
EGF/EGFR dimer	0.013	0.092	0.14	34	-0.23	56	90
SOS1	0.026	0.005	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	0.005	0.1	0.14	9	-0.25	61	70

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.02	0.069	0.3	2	-0.21	15	17
alphaM/beta2 Integrin/GPIbA	0.021	0.067	0.28	3	-0.16	22	25
alphaM/beta2 Integrin/proMMP-9	0.073	0.093	0.28	6	-0.19	16	22
PLAUR	0.029	0.019	0.17	8	-10000	0	8
HMGB1	0.008	0.036	-10000	0	-0.12	3	3
alphaM/beta2 Integrin/Talin	0.024	0.061	0.25	2	-0.19	7	9
AGER	0.013	0.053	0.17	19	-0.28	3	22
RAP1A	0.026	0.005	-10000	0	-10000	0	0
SELPLG	0.027	0.023	0.17	6	-0.31	1	7
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.012	0.12	0.28	3	-0.2	114	117
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.1	0.085	0.17	258	-0.31	5	263
CYR61	0.022	0.051	0.17	7	-0.31	10	17
TLN1	0.026	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.013	0.098	-10000	0	-0.25	38	38
RHOA	0.026	0.005	-10000	0	-10000	0	0
P-selectin oligomer	0.02	0.045	-10000	0	-0.31	9	9
MYH2	-0.05	0.11	-10000	0	-0.32	46	46
MST1R	0.02	0.052	0.17	4	-0.31	11	15
leukocyte activation during inflammatory response	-0.03	0.11	-10000	0	-0.19	141	141
APOB	-0.047	0.14	0.17	2	-0.31	108	110
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.018	0.048	0.17	1	-0.31	10	11
JAM3	0.016	0.058	-10000	0	-0.31	15	15
GP1BA	0.021	0.042	0.17	3	-0.31	7	10
alphaM/beta2 Integrin/CTGF	0.016	0.076	0.25	2	-0.18	33	35
alphaM/beta2 Integrin	-0.028	0.1	-10000	0	-0.28	41	41
JAM3 homodimer	0.016	0.058	-10000	0	-0.31	15	15
ICAM2	0.026	0.017	0.17	1	-0.31	1	2
ICAM1	0.03	0.022	0.17	11	-10000	0	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.027	0.1	0.19	1	-0.28	41	42
cell adhesion	0.02	0.066	0.28	3	-0.16	22	25
NFKB1	-0.055	0.17	0.4	4	-0.33	115	119
THY1	0.028	0.025	0.17	8	-0.31	1	9
RhoA/GDP	0.019	0.004	-10000	0	-10000	0	0
Lipoprotein(a)	-0.033	0.11	0.13	8	-0.2	146	154
alphaM/beta2 Integrin/LRP/tPA	0.029	0.07	0.25	2	-0.21	11	13
IL6	-0.11	0.25	0.48	4	-0.55	106	110
ITGB2	0.009	0.042	0.17	5	-0.14	5	10
elevation of cytosolic calcium ion concentration	0.029	0.075	0.34	2	-0.19	17	19
alphaM/beta2 Integrin/JAM2/JAM3	0.028	0.08	0.25	2	-0.21	23	25
JAM2	0.023	0.034	-10000	0	-0.31	5	5
alphaM/beta2 Integrin/ICAM1	0.053	0.082	0.26	4	-0.18	17	21
alphaM/beta2 Integrin/uPA/Plg	0.032	0.077	0.3	2	-0.2	17	19
RhoA/GTP	-0.036	0.11	0.16	2	-0.32	40	42
positive regulation of phagocytosis	-0.015	0.093	0.2	3	-0.26	26	29
Ron/MSP	0.045	0.053	0.15	58	-0.22	11	69
alphaM/beta2 Integrin/uPAR/uPA	0.032	0.077	0.34	2	-0.2	17	19
alphaM/beta2 Integrin/uPAR	0.025	0.064	0.3	2	-0.18	8	10
PLAU	0.019	0.05	0.17	1	-0.31	11	12
PLAT	0.021	0.042	0.17	12	-0.31	5	17
actin filament polymerization	-0.048	0.11	-10000	0	-0.3	46	46
MST1	0.043	0.047	0.17	56	-10000	0	56
alphaM/beta2 Integrin/lipoprotein(a)	-0.027	0.12	-10000	0	-0.19	141	141
TNF	-0.081	0.18	0.49	4	-0.37	110	114
RAP1B	0.026	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.019	0.071	0.3	2	-0.18	25	27
fibrinolysis	0.03	0.075	0.29	2	-0.2	17	19
HCK	0.024	0.031	0.17	1	-0.31	4	5
dendritic cell antigen processing and presentation	-0.027	0.1	0.19	1	-0.28	41	42
VTN	0.007	0.12	0.17	51	-0.31	51	102
alphaM/beta2 Integrin/CYR61	0.022	0.07	0.3	2	-0.17	24	26
LPA	-0.013	0.11	0.17	7	-0.31	60	67
LRP1	0.026	0.017	0.17	1	-0.31	1	2
cell migration	0.016	0.075	0.19	10	-0.2	22	32
FN1	0.02	0.052	0.17	4	-0.31	11	15
alphaM/beta2 Integrin/Thy1	0.025	0.065	0.3	2	-0.15	17	19
MPO	0	0.089	-10000	0	-0.31	38	38
KNG1	0.037	0.05	0.17	58	-10000	0	58
RAP1/GDP	0.034	0.01	-10000	0	-10000	0	0
ROCK1	-0.035	0.11	-10000	0	-0.31	37	37
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.029	0.033	0.17	23	-10000	0	23
CTGF	0.014	0.065	0.17	1	-0.31	19	20
alphaM/beta2 Integrin/Hck	0.023	0.066	0.3	2	-0.15	20	22
ITGAM	0.005	0.048	0.18	2	-0.21	9	11
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.032	0.074	0.31	3	-0.22	12	15
HP	0.026	0.079	0.17	51	-0.31	17	68
leukocyte adhesion	-0.003	0.11	0.28	2	-0.26	37	39
SELP	0.02	0.045	-10000	0	-0.31	9	9

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.005	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.028	0.065	-10000	0	-0.16	49	49
regulation of S phase of mitotic cell cycle	-0.004	0.072	-10000	0	-0.21	45	45
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
HRAS	0.028	0.017	0.17	6	-10000	0	6
SHBG/T-DHT	0.015	0.019	0.11	5	-0.15	4	9
PELP1	0.024	0.01	-10000	0	-10000	0	0
AKT1	-0.005	0.004	-10000	0	-10000	0	0
MAP2K1	-0.039	0.065	0.21	7	-0.22	13	20
T-DHT/AR	-0.002	0.065	-10000	0	-0.21	43	43
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.008	84	84
GNAI2	0.026	0.005	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
mol:GDP	-0.033	0.097	-10000	0	-0.34	43	43
cell proliferation	-0.07	0.17	0.32	9	-0.41	80	89
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
FOS	-0.12	0.28	0.32	4	-0.73	84	88
mol:Ca2+	-0.011	0.027	-10000	0	-0.067	79	79
MAPK3	-0.049	0.12	0.31	11	-0.29	71	82
MAPK1	-0.03	0.097	0.21	6	-0.29	25	31
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:IP3	-0.001	0.002	-10000	0	-0.005	84	84
cAMP biosynthetic process	0.002	0.024	0.086	4	-0.17	3	7
GNG2	0.023	0.037	-10000	0	-0.31	6	6
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	84	84
HRAS/GTP	0.014	0.068	-10000	0	-0.16	44	44
actin cytoskeleton reorganization	0.032	0.026	-10000	0	-0.18	4	4
SRC	0.025	0.007	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	84	84
PI3K	0.028	0.029	-10000	0	-0.2	6	6
apoptosis	0.06	0.17	0.41	82	-0.28	7	89
T-DHT/AR/PELP1	0.013	0.06	-10000	0	-0.18	43	43
HRAS/GDP	-0.018	0.1	-10000	0	-0.33	43	43
CREB1	-0.065	0.18	0.29	7	-0.44	82	89
RAC1-CDC42/GTP	0.04	0.03	-10000	0	-0.18	4	4
AR	-0.004	0.095	-10000	0	-0.31	43	43
GNB1	0.027	0.004	-10000	0	-10000	0	0
RAF1	-0.032	0.06	0.22	8	-0.2	11	19
RAC1-CDC42/GDP	0.005	0.1	-10000	0	-0.31	43	43
T-DHT/AR/PELP1/Src	0.019	0.063	-10000	0	-0.16	43	43
MAP2K2	-0.039	0.065	0.21	7	-0.21	15	22
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.072	-10000	0	-0.21	45	45
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
SHBG	0.022	0.032	0.17	5	-0.31	3	8
Gi family/GNB1/GNG2/GDP	-0.05	0.14	-10000	0	-0.35	74	74
mol:T-DHT	0	0.002	-10000	0	-0.004	54	54
RAC1	0.025	0.008	-10000	0	-10000	0	0
GNRH1	-0.005	0.008	-10000	0	-10000	0	0
Gi family/GTP	-0.035	0.094	0.11	1	-0.26	60	61
CDC42	0.027	0.003	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
CDC42/GTP	-0.013	0.11	0.2	1	-0.24	70	71
PLCG1	-0.023	0.1	0.21	1	-0.25	67	68
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.026	0.005	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
G12/G13	0.035	0.013	-10000	0	-10000	0	0
cell migration	-0.014	0.1	0.2	1	-0.24	70	71
S1PR5	-0.026	0.12	-10000	0	-0.31	78	78
S1PR4	0.031	0.033	0.17	20	-0.31	1	21
MAPK3	-0.023	0.1	0.21	1	-0.25	67	68
MAPK1	-0.021	0.098	0.21	1	-0.25	65	66
S1P/S1P5/Gi	-0.045	0.14	-10000	0	-0.28	112	112
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
CDC42/GDP	0.02	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.004	0.072	-10000	0	-0.18	67	67
RHOA	0.003	0.062	0.19	44	-10000	0	44
S1P/S1P4/Gi	-0.018	0.11	-10000	0	-0.25	74	74
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
S1P/S1P4/G12/G13	0.048	0.026	-10000	0	-10000	0	0
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
CDC42	0.027	0.003	-10000	0	-10000	0	0

×

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
Noncanonical Wnts/FZD	-0.019	0.1	-10000	0	-0.24	71	71
FZD6	0.021	0.011	-10000	0	-10000	0	0
WNT6	-0.03	0.13	0.17	7	-0.31	87	94
WNT4	0.023	0.034	-10000	0	-0.31	5	5
FZD3	0.02	0.012	-10000	0	-10000	0	0
WNT5A	0.015	0.074	0.17	12	-0.31	22	34
WNT11	0.027	0.054	0.17	23	-0.31	8	31

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.016	-10000	0	-0.31	1	1
CCL5	0.021	0.055	0.17	7	-0.31	12	19
SDCBP	0.022	0.01	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.013	0.1	0.27	8	-0.35	19	27
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.002	0.1	0.23	8	-0.34	20	28
Syndecan-1/Syntenin	0	0.095	0.28	5	-0.32	17	22
MAPK3	-0.005	0.099	0.23	13	-0.32	19	32
HGF/MET	0.007	0.095	-10000	0	-0.26	50	50
TGFB1/TGF beta receptor Type II	0.026	0.016	-10000	0	-0.31	1	1
BSG	0.027	0.007	0.17	1	-10000	0	1
keratinocyte migration	-0.002	0.1	0.22	11	-0.34	20	31
Syndecan-1/RANTES	-0.001	0.11	0.24	12	-0.33	25	37
Syndecan-1/CD147	0.013	0.11	0.28	8	-0.33	19	27
Syndecan-1/Syntenin/PIP2	-0.002	0.09	0.28	2	-0.32	16	18
LAMA5	0.026	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.003	0.089	0.27	2	-0.32	16	18
MMP7	0.017	0.1	0.17	50	-0.31	35	85
HGF	0.011	0.075	0.17	9	-0.31	24	33
Syndecan-1/CASK	-0.019	0.093	0.18	5	-0.33	21	26
Syndecan-1/HGF/MET	-0.011	0.13	0.22	1	-0.33	42	43
regulation of cell adhesion	-0.013	0.096	0.24	13	-0.32	19	32
HPSE	0.017	0.066	0.17	8	-0.31	18	26
positive regulation of cell migration	-0.013	0.1	0.27	8	-0.35	19	27
SDC1	-0.013	0.098	0.24	6	-0.36	18	24
Syndecan-1/Collagen	-0.013	0.1	0.27	8	-0.35	19	27
PPIB	0.028	0.012	0.17	3	-10000	0	3
MET	-0.004	0.093	-10000	0	-0.31	42	42
PRKACA	0.027	0.003	-10000	0	-10000	0	0
MMP9	0.1	0.085	0.17	258	-0.31	5	263
MAPK1	-0.005	0.1	0.22	15	-0.32	19	34
homophilic cell adhesion	-0.011	0.1	0.25	13	-0.35	19	32
MMP1	0.024	0.096	0.17	60	-0.31	29	89

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.017	0.11	-10000	0	-0.18	101	101
SMAD6-7/SMURF1	0.04	0.037	-10000	0	-0.18	9	9
NOG	-0.011	0.11	0.17	1	-0.31	55	56
SMAD9	-0.073	0.19	-10000	0	-0.43	102	102
SMAD4	0.025	0.008	-10000	0	-10000	0	0
SMAD5	-0.007	0.072	0.21	2	-0.27	19	21
BMP7/USAG1	-0.073	0.15	-10000	0	-0.26	175	175
SMAD5/SKI	0.006	0.081	0.23	3	-0.26	19	22
SMAD1	0.02	0.032	-10000	0	-0.23	1	1
BMP2	0.006	0.08	0.17	1	-0.31	30	31
SMAD1/SMAD1/SMAD4	0.03	0.036	-10000	0	-10000	0	0
BMPR1A	0.024	0.017	-10000	0	-0.31	1	1
BMPR1B	0.025	0.029	0.17	3	-0.31	3	6
BMPR1A-1B/BAMBI	0.05	0.033	-10000	0	-0.17	4	4
AHSG	0.03	0.04	0.17	35	-10000	0	35
CER1	0.022	0.021	0.17	9	-10000	0	9
BMP2-4/CER1	0.026	0.08	-10000	0	-0.22	41	41
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.007	0.1	0.19	1	-0.32	33	34
BMP2-4 (homodimer)	0.014	0.087	0.14	1	-0.26	41	42
RGMB	0.024	0.009	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.067	0.043	0.19	2	-0.17	3	5
RGMA	0.012	0.069	-10000	0	-0.31	22	22
SMURF1	0.024	0.008	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.011	0.095	-10000	0	-0.32	33	33
BMP2-4/USAG1	-0.038	0.13	-10000	0	-0.22	155	155
SMAD6/SMURF1/SMAD5	0.004	0.073	0.26	1	-0.27	15	16
SOSTDC1	-0.079	0.15	-10000	0	-0.31	151	151
BMP7/BMPR2/BMPR1A-1B	0.019	0.09	-10000	0	-0.16	90	90
SKI	0.027	0.004	-10000	0	-10000	0	0
BMP6 (homodimer)	0.043	0.047	0.17	57	-10000	0	57
HFE2	0.037	0.046	0.17	50	-10000	0	50
ZFYVE16	0.025	0.007	-10000	0	-10000	0	0
MAP3K7	0.022	0.01	-10000	0	-10000	0	0
BMP2-4/CHRD	0.035	0.087	-10000	0	-0.22	41	41
SMAD5/SMAD5/SMAD4	0.007	0.079	0.3	2	-0.26	17	19
MAPK1	0.027	0.004	-10000	0	-10000	0	0
TAK1/TAB family	0.003	0.087	-10000	0	-0.29	25	25
BMP7 (homodimer)	-0.034	0.13	0.17	1	-0.31	89	90
NUP214	0.026	0.006	-10000	0	-10000	0	0
BMP6/FETUA	0.051	0.046	0.16	53	-10000	0	53
SMAD1/SKI	0.037	0.043	0.29	3	-0.22	2	5
SMAD6	0.021	0.045	-10000	0	-0.31	9	9
CTDSP2	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/FETUA	0.031	0.083	-10000	0	-0.23	39	39
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.008	0.1	0.17	31	-0.31	41	72
BMPR2 (homodimer)	0.027	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.048	0.02	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.034	0.026	0.14	2	-0.2	4	6
CHRDL1	-0.058	0.15	-10000	0	-0.31	125	125
ENDOFIN/SMAD1	0.035	0.045	0.32	4	-0.22	2	6
SMAD6-7/SMURF1/SMAD1	0.044	0.048	0.28	2	-10000	0	2
SMAD6/SMURF1	0.024	0.008	-10000	0	-10000	0	0
BAMBI	0.033	0.029	0.17	20	-10000	0	20
SMURF2	0.026	0.005	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.022	0.14	-10000	0	-0.23	128	128
BMP2-4/GREM1	0.018	0.11	-10000	0	-0.22	71	71
SMAD7	0.025	0.008	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.065	0.19	-10000	0	-0.4	110	110
SMAD1/SMAD6	0.031	0.038	0.28	2	-0.22	2	4
TAK1/SMAD6	0.031	0.017	-10000	0	-10000	0	0
BMP7	-0.034	0.13	0.17	1	-0.31	89	90
BMP6	0.043	0.048	0.17	57	-10000	0	57
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.009	0.096	-10000	0	-0.32	31	31
PPM1A	0.027	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.036	0.046	0.35	3	-0.22	2	5
SMAD7/SMURF1	0.033	0.016	-10000	0	-10000	0	0
CTDSPL	0.026	0.005	-10000	0	-10000	0	0
PPP1CA	0.026	0.006	-10000	0	-10000	0	0
XIAP	0.027	0.001	-10000	0	-10000	0	0
CTDSP1	0.027	0.003	-10000	0	-10000	0	0
PPP1R15A	0.028	0.014	0.17	4	-10000	0	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.034	0.14	-10000	0	-0.4	47	47
CHRD	0.036	0.049	0.17	41	-0.31	3	44
BMPR2	0.027	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.012	0.1	-10000	0	-0.28	48	48
BMP4	0.01	0.074	-10000	0	-0.31	25	25
FST	0.003	0.086	0.17	3	-0.31	34	37
BMP2-4/NOG	0.007	0.11	-10000	0	-0.24	76	76
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.03	0.085	-10000	0	-0.16	75	75

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.001	0.021	-10000	0	-10000	0	0
NFATC2	-0.028	0.071	-10000	0	-0.18	77	77
NFATC3	0.001	0.02	-10000	0	-10000	0	0
CD40LG	-0.074	0.15	0.27	2	-0.37	69	71
PTGS2	-0.088	0.17	0.33	1	-0.4	91	92
JUNB	0.024	0.053	0.17	12	-0.31	10	22
CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.02	-10000	0	-10000	0	0
CaM/Ca2+	0.011	0.02	-10000	0	-10000	0	0
CALM1	0.02	0.018	-10000	0	-10000	0	0
JUN	0.018	0.036	0.17	1	-0.32	4	5
mol:Ca2+	-0.003	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.017	0.006	-10000	0	-10000	0	0
FOSL1	-0.012	0.13	0.17	33	-0.31	70	103
CREM	0.026	0.004	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.008	0.1	-10000	0	-0.24	32	32
FOS	-0.031	0.13	0.17	4	-0.32	78	82
IFNG	-0.067	0.13	0.27	2	-0.34	61	63
AP-1/NFAT1-c-4	-0.031	0.18	0.36	1	-0.37	68	69
FASLG	-0.071	0.14	0.33	1	-0.36	64	65
NFAT1-c-4/ICER1	-0.019	0.077	-10000	0	-0.2	31	31
IL2RA	-0.064	0.14	0.25	3	-0.35	63	66
FKBP12/FK506	0.02	0.003	-10000	0	-10000	0	0
CSF2	-0.071	0.13	-10000	0	-0.34	62	62
JunB/Fra1/NFAT1-c-4	-0.023	0.11	0.22	4	-0.23	59	63
IL4	-0.072	0.13	-10000	0	-0.34	62	62
IL2	-0.005	0.15	-10000	0	-0.94	12	12
IL3	-0.012	0.14	-10000	0	-0.65	21	21
FKBP1A	0.027	0.004	-10000	0	-10000	0	0
BATF3	0.032	0.031	0.17	22	-10000	0	22
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.026	0.006	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.06	0.07	0.28	10	-0.19	21	31
MAP4K1	0.031	0.048	0.17	26	-0.31	5	31
MAP3K8	0.018	0.054	0.17	1	-0.31	13	14
PRKCB	-0.047	0.14	-10000	0	-0.31	107	107
DBNL	0.025	0.008	-10000	0	-10000	0	0
CRKL	0.026	0.005	-10000	0	-10000	0	0
MAP3K1	0.007	0.058	0.17	1	-0.36	6	7
JUN	-0.12	0.25	0.35	1	-0.54	122	123
MAP3K7	0.009	0.049	0.17	1	-0.34	4	5
GRAP2	0.016	0.06	0.17	2	-0.31	16	18
CRK	0.025	0.007	-10000	0	-10000	0	0
MAP2K4	0.002	0.073	0.27	5	-0.35	10	15
LAT	0.029	0.032	0.17	13	-0.31	2	15
LCP2	0.025	0.03	0.17	4	-0.31	3	7
MAPK8	-0.12	0.26	-10000	0	-0.56	122	122
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.017	0.064	0.18	1	-0.37	6	7
LAT/GRAP2/SLP76/HPK1/HIP-55	0.065	0.069	0.29	9	-0.18	19	28

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.009	0.044	-10000	0	-0.34	6	6
Crk/p130 Cas/Paxillin	-0.022	0.086	-10000	0	-0.24	51	51
JUN	-0.023	0.082	-10000	0	-0.3	24	24
HRAS	0.028	0.017	0.17	6	-10000	0	6
RET51/GFRalpha1/GDNF/GRB10	0.042	0.093	-10000	0	-0.19	54	54
RAP1A	0.026	0.005	-10000	0	-10000	0	0
FRS2	0.026	0.006	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.044	0.099	-10000	0	-0.19	60	60
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.019	0.083	-10000	0	-0.19	60	60
RHOA	0.026	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.034	0.09	-10000	0	-0.18	60	60
GRB7	0.027	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF	0.044	0.098	-10000	0	-0.19	61	61
MAPKKK cascade	0.011	0.082	-10000	0	-0.21	51	51
BCAR1	0.022	0.011	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.017	0.082	-10000	0	-0.18	65	65
lamellipodium assembly	-0.012	0.085	-10000	0	-0.23	52	52
RET51/GFRalpha1/GDNF/SHC	0.042	0.097	-10000	0	-0.19	60	60
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
RET9/GFRalpha1/GDNF/SHC	0.021	0.072	-10000	0	-0.17	55	55
RET9/GFRalpha1/GDNF/Shank3	0.022	0.072	-10000	0	-0.17	57	57
MAPK3	-0.03	0.076	0.23	16	-0.28	11	27
DOK1	0.026	0.016	-10000	0	-0.31	1	1
DOK6	0.017	0.065	0.17	14	-0.31	16	30
PXN	0.026	0.006	-10000	0	-10000	0	0
neurite development	-0.028	0.069	0.21	12	-0.26	14	26
DOK5	0.014	0.073	0.17	9	-0.31	22	31
GFRA1	-0.001	0.093	0.17	1	-0.31	41	42
MAPK8	-0.017	0.082	-10000	0	-0.22	54	54
HRAS/GTP	0.034	0.1	0.21	2	-0.22	53	55
tube development	0.022	0.072	0.2	9	-0.16	55	64
MAPK1	-0.029	0.079	0.22	19	-0.27	13	32
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.003	0.067	-10000	0	-0.19	53	53
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
SRC	0.026	0.006	-10000	0	-10000	0	0
PDLIM7	0.019	0.053	0.17	2	-0.31	12	14
RET51/GFRalpha1/GDNF/Dok6	0.042	0.1	-10000	0	-0.19	67	67
SHC1	0.026	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.039	0.1	-10000	0	-0.19	61	61
RET51/GFRalpha1/GDNF/Dok5	0.038	0.11	0.25	5	-0.21	68	73
PRKCA	0.011	0.069	-10000	0	-0.31	22	22
HRAS/GDP	0.021	0.012	0.12	6	-10000	0	6
CREB1	-0.007	0.088	-10000	0	-0.23	56	56
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.004	0.071	-10000	0	-0.2	53	53
RET51/GFRalpha1/GDNF/Grb7	0.043	0.098	-10000	0	-0.19	62	62
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.044	0.075	0.17	81	-0.31	10	91
DOK4	0.022	0.031	-10000	0	-0.31	4	4
JNK cascade	-0.021	0.083	0.24	2	-0.3	24	26
RET9/GFRalpha1/GDNF/FRS2	0.022	0.071	-10000	0	-0.17	55	55
SHANK3	0.027	0.004	-10000	0	-10000	0	0
RASA1	0.025	0.016	-10000	0	-0.31	1	1
NCK1	0.025	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.004	0.07	-10000	0	-0.2	53	53
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0	0.078	-10000	0	-0.2	60	60
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.001	0.086	0.15	1	-0.22	55	56
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.001	0.082	0.15	1	-0.21	59	60
PI3K	-0.021	0.12	0.24	3	-0.32	57	60
SOS1	0.026	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.032	0.073	-10000	0	-0.16	55	55
GRB10	0.025	0.008	-10000	0	-10000	0	0
activation of MAPKK activity	-0.006	0.081	-10000	0	-0.22	48	48
RET51/GFRalpha1/GDNF/FRS2	0.044	0.095	-10000	0	-0.18	60	60
GAB1	0.026	0.016	-10000	0	-0.31	1	1
IRS1	0.017	0.058	-10000	0	-0.31	15	15
IRS2	0.026	0.02	0.17	3	-0.31	1	4
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.002	0.087	0.15	1	-0.22	61	62
RET51/GFRalpha1/GDNF/PKC alpha	0.035	0.11	-10000	0	-0.21	69	69
GRB2	0.026	0.005	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GDNF	0.009	0.07	-10000	0	-0.31	23	23
RAC1	0.025	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.039	0.11	-10000	0	-0.2	69	69
Rac1/GTP	-0.012	0.1	-10000	0	-0.27	52	52
RET9/GFRalpha1/GDNF	0.008	0.073	0.13	1	-0.19	57	58
GFRalpha1/GDNF	0.006	0.086	0.14	1	-0.23	57	58

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.005	0.012	0.25	1	-10000	0	1
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.035	0.031	0.14	8	-0.21	5	13
STXBP1	0.024	0.022	-10000	0	-0.31	2	2
ACh/CHRNA1	0.026	0.065	0.14	82	-0.091	57	139
RAB3GAP2/RIMS1/UNC13B	0.047	0.031	-10000	0	-0.18	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.023	0.038	0.17	6	-0.31	5	11
mol:ACh	-0.01	0.049	0.09	36	-0.11	62	98
RAB3GAP2	0.026	0.006	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.015	0.068	0.16	1	-0.16	43	44
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.026	0.065	0.14	82	-0.091	57	139
UNC13B	0.027	0.01	0.17	2	-10000	0	2
CHRNA1	0.05	0.056	0.17	84	-10000	0	84
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.009	0.08	0.12	7	-0.18	72	79
SNAP25	-0.027	0.077	-10000	0	-0.22	68	68
VAMP2	0.004	0.001	-10000	0	-10000	0	0
SYT1	-0.026	0.13	0.17	9	-0.31	80	89
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.021	0.015	0.2	1	-0.18	1	2
STX1A/SNAP25 fragment 1/VAMP2	0.015	0.068	0.16	1	-0.16	43	44

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.029	0.055	-10000	0	-0.17	29	29
fibroblast growth factor receptor signaling pathway	0.028	0.055	-10000	0	-0.17	29	29
LAMA1	0.02	0.07	0.17	22	-0.31	17	39
PRNP	0.026	0.004	-10000	0	-10000	0	0
GPC1/SLIT2	0.008	0.083	-10000	0	-0.22	58	58
SMAD2	-0.011	0.042	0.18	18	-0.17	9	27
GPC1/PrPc/Cu2+	0.035	0.012	-10000	0	-0.18	1	1
GPC1/Laminin alpha1	0.033	0.053	-10000	0	-0.21	18	18
TDGF1	-0.009	0.1	0.17	6	-0.31	53	59
CRIPTO/GPC1	0.012	0.08	-10000	0	-0.21	53	53
APP/GPC1	0.037	0.019	-10000	0	-0.21	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.03	0.052	0.17	1	-0.18	50	51
FLT1	0.025	0.028	0.17	2	-0.31	3	5
GPC1/TGFB/TGFBR1/TGFBR2	0.046	0.035	-10000	0	-0.18	9	9
SERPINC1	0.034	0.037	0.17	31	-10000	0	31
FYN	-0.028	0.05	0.17	1	-0.18	46	47
FGR	-0.032	0.053	0.17	1	-0.18	54	55
positive regulation of MAPKKK cascade	-0.034	0.11	0.28	10	-0.28	50	60
SLIT2	-0.013	0.11	-10000	0	-0.31	58	58
GPC1/NRG	0	0.079	-10000	0	-0.21	57	57
NRG1	-0.019	0.1	-10000	0	-0.31	57	57
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.04	0.058	0.24	1	-0.18	28	29
LYN	-0.026	0.047	-10000	0	-0.18	40	40
mol:Spermine	-0.007	0.009	-10000	0	-0.21	1	1
cell growth	0.028	0.055	-10000	0	-0.17	29	29
BMP signaling pathway	-0.026	0.015	0.31	1	-10000	0	1
SRC	-0.031	0.052	0.17	1	-0.18	52	53
TGFBR1	0.026	0.006	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.063	0.099	0.17	161	-0.31	18	179
GPC1	0.026	0.015	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.026	0.006	-10000	0	-10000	0	0
VEGFA	0.01	0.077	0.17	5	-0.31	26	31
BLK	-0.032	0.074	0.26	1	-0.2	69	70
HCK	-0.032	0.054	0.17	1	-0.18	55	56
FGF2	0.005	0.082	0.17	1	-0.31	31	32
FGFR1	0.02	0.019	-10000	0	-0.31	1	1
VEGFR1 homodimer	0.024	0.028	0.17	2	-0.31	3	5
TGFBR2	0.019	0.05	-10000	0	-0.31	11	11
cell death	0.037	0.019	-10000	0	-0.21	2	2
ATIII/GPC1	0.043	0.029	0.14	30	-0.21	1	31
PLA2G2A/GPC1	0.063	0.073	-10000	0	-0.21	19	19
LCK	-0.03	0.053	0.17	1	-0.18	51	52
neuron differentiation	-0.001	0.079	-10000	0	-0.21	57	57
PrPc/Cu2+	0.02	0.003	-10000	0	-10000	0	0
APP	0.025	0.022	-10000	0	-0.31	2	2
TGFBR2 (dimer)	0.019	0.05	-10000	0	-0.31	11	11

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.026	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.012	0.072	-10000	0	-0.21	38	38
NT3 (dimer)/TRKC	-0.025	0.13	-10000	0	-0.26	102	102
NT3 (dimer)/TRKB	-0.012	0.12	-10000	0	-0.23	106	106
SHC/Grb2/SOS1/GAB1/PI3K	0.018	0.03	-10000	0	-0.2	7	7
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0
BDNF	-0.039	0.13	-10000	0	-0.31	96	96
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
NTRK1	0.01	0.078	0.17	8	-0.31	26	34
NTRK2	-0.016	0.11	0.17	1	-0.31	62	63
NTRK3	-0.035	0.13	-10000	0	-0.31	91	91
NT-4/5 (dimer)/TRKB	-0.036	0.14	-10000	0	-0.24	147	147
neuron apoptosis	0.051	0.16	0.38	70	-0.23	1	71
SHC 2-3/Grb2	-0.056	0.18	0.24	1	-0.42	70	71
SHC1	0.026	0.006	-10000	0	-10000	0	0
SHC2	-0.051	0.15	-10000	0	-0.42	52	52
SHC3	-0.073	0.19	0.25	1	-0.48	70	71
STAT3 (dimer)	0.031	0.007	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.006	0.11	-10000	0	-0.22	81	81
RIN/GDP	0.006	0.094	0.26	18	-0.22	23	41
GIPC1	0.027	0.003	-10000	0	-10000	0	0
KRAS	0.025	0.007	-10000	0	-10000	0	0
DNAJA3	-0.029	0.095	-10000	0	-0.25	63	63
RIN/GTP	0.022	0.028	0.12	31	-0.11	2	33
CCND1	0.014	0.006	-10000	0	-10000	0	0
MAGED1	0.027	0.007	0.17	1	-10000	0	1
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.048	0.14	-10000	0	-0.31	109	109
SHC/GRB2/SOS1	0.049	0.018	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.061	0.1	0.24	1	-0.2	48	49
TRKA/NEDD4-2	0.024	0.06	0.14	14	-0.21	25	39
ELMO1	0.023	0.023	-10000	0	-0.31	2	2
RhoG/GTP/ELMO1/DOCK1	0.029	0.025	-10000	0	-0.18	5	5
NGF	0.013	0.069	0.17	2	-0.31	21	23
HRAS	0.028	0.017	0.17	6	-10000	0	6
DOCK1	0.023	0.03	-10000	0	-0.31	4	4
GAB2	0.026	0.006	-10000	0	-10000	0	0
RIT2	0.031	0.038	0.17	31	-10000	0	31
RIT1	0.026	0.006	-10000	0	-10000	0	0
FRS2	0.026	0.006	-10000	0	-10000	0	0
DNM1	0.025	0.018	0.17	1	-0.31	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.012	0.1	-10000	0	-0.24	65	65
mol:GDP	-0.009	0.12	0.3	19	-0.31	28	47
NGF (dimer)	0.013	0.068	0.17	2	-0.31	21	23
RhoG/GDP	0.017	0.016	-10000	0	-0.21	2	2
RIT1/GDP	0.001	0.089	0.26	13	-0.22	24	37
TIAM1	0.023	0.03	-10000	0	-0.31	4	4
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
BDNF (dimer)/TRKB	-0.015	0.13	-10000	0	-0.24	111	111
KIDINS220/CRKL/C3G	0.037	0.011	-10000	0	-10000	0	0
SHC/RasGAP	0.035	0.017	-10000	0	-0.21	1	1
FRS2 family/SHP2	0.05	0.018	-10000	0	-0.18	1	1
SHC/GRB2/SOS1/GAB1	0.061	0.025	-10000	0	-0.17	1	1
RIT1/GTP	0.019	0.004	-10000	0	-10000	0	0
NT3 (dimer)	-0.005	0.095	-10000	0	-0.31	44	44
RAP1/GDP	-0.005	0.068	0.14	3	-0.2	20	23
KIDINS220/CRKL	0.026	0.005	-10000	0	-10000	0	0
BDNF (dimer)	-0.039	0.13	-10000	0	-0.31	96	96
ubiquitin-dependent protein catabolic process	0.026	0.073	-10000	0	-0.18	44	44
Schwann cell development	-0.022	0.026	-10000	0	-0.1	4	4
EHD4	0.026	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.062	0.023	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.023	0.029	-10000	0	-0.17	2	2
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.044	0.14	-10000	0	-0.24	141	141
ABL1	0.026	0.006	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
Rap1/GTP	-0.005	0.084	-10000	0	-0.32	18	18
STAT3	0.031	0.007	-10000	0	-10000	0	0
axon guidance	-0.05	0.13	-10000	0	-0.23	148	148
MAPK3	-0.038	0.06	0.18	11	-0.2	37	48
MAPK1	-0.039	0.061	0.18	12	-0.19	40	52
CDC42/GDP	0.003	0.092	0.25	17	-0.22	24	41
NTF3	-0.005	0.095	-10000	0	-0.31	44	44
NTF4	-0.048	0.14	-10000	0	-0.31	109	109
NGF (dimer)/TRKA/FAIM	0.028	0.071	-10000	0	-0.18	43	43
PI3K	0.031	0.034	-10000	0	-0.24	6	6
FRS3	0.027	0.003	-10000	0	-10000	0	0
FAIM	0.025	0.007	-10000	0	-10000	0	0
GAB1	0.026	0.016	-10000	0	-0.31	1	1
RASGRF1	-0.049	0.12	-10000	0	-0.3	69	69
SOS1	0.026	0.005	-10000	0	-10000	0	0
MCF2L	-0.053	0.088	-10000	0	-0.22	93	93
RGS19	0.026	0.009	0.17	1	-10000	0	1
CDC42	0.027	0.003	-10000	0	-10000	0	0
RAS family/GTP	0	0.11	0.28	6	-0.44	13	19
Rac1/GDP	0.001	0.083	0.26	9	-0.22	23	32
NGF (dimer)/TRKA/GRIT	0.016	0.066	0.13	10	-0.18	46	56
neuron projection morphogenesis	-0.033	0.18	-10000	0	-0.77	17	17
NGF (dimer)/TRKA/NEDD4-2	0.027	0.073	-10000	0	-0.18	44	44
MAP2K1	-0.001	0.07	0.22	36	-0.16	1	37
NGFR	-0.001	0.093	-10000	0	-0.31	41	41
NGF (dimer)/TRKA/GIPC/GAIP	0.006	0.06	-10000	0	-0.19	40	40
RAS family/GTP/PI3K	0.016	0.027	-10000	0	-0.2	6	6
FRS2 family/SHP2/GRB2/SOS1	0.07	0.03	-10000	0	-0.16	1	1
NRAS	0.026	0.016	-10000	0	-0.31	1	1
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
PRKCI	0.025	0.01	0.17	1	-10000	0	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.027	0.004	-10000	0	-10000	0	0
MAPKKK cascade	-0.06	0.21	-10000	0	-0.55	70	70
RASA1	0.025	0.016	-10000	0	-0.31	1	1
TRKA/c-Abl	0.026	0.057	0.14	8	-0.21	24	32
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.001	0.12	-10000	0	-0.22	112	112
NGF (dimer)/TRKA/p62/Atypical PKCs	0.048	0.073	-10000	0	-0.16	41	41
MATK	0.089	0.075	0.17	213	-0.31	1	214
NEDD4L	0.027	0.026	0.17	13	-10000	0	13
RAS family/GDP	-0.02	0.051	-10000	0	-0.16	34	34
NGF (dimer)/TRKA	-0.027	0.1	-10000	0	-0.26	70	70
Rac1/GTP	-0.04	0.092	-10000	0	-0.25	55	55
FRS2 family/SHP2/CRK family	0.069	0.03	-10000	0	-0.16	1	1

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.025	0.016	0.17	4	-10000	0	4
LAT2	-0.009	0.083	0.21	3	-0.28	29	32
AP1	0	0.14	0.27	3	-0.4	34	37
mol:PIP3	0.011	0.15	0.33	41	-0.36	24	65
IKBKB	0.009	0.12	0.28	52	-0.21	34	86
AKT1	-0.004	0.12	0.34	33	-0.25	17	50
IKBKG	-0.003	0.11	0.25	39	-0.22	36	75
MS4A2	0.014	0.068	0.18	4	-0.31	19	23
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
MAP3K1	0.009	0.12	0.28	31	-0.34	19	50
mol:Ca2+	0.014	0.12	0.3	42	-0.28	24	66
LYN	0.022	0.012	-10000	0	-10000	0	0
CBLB	-0.008	0.083	0.16	2	-0.28	30	32
SHC1	0.026	0.006	-10000	0	-10000	0	0
RasGAP/p62DOK	0.04	0.041	-10000	0	-0.16	18	18
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
PLD2	-0.015	0.085	0.27	21	-0.22	24	45
PTPN13	0	0.13	0.35	2	-0.53	14	16
PTPN11	0.023	0.023	-10000	0	-0.32	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.014	0.13	0.39	32	-0.28	18	50
SYK	0.023	0.037	0.17	1	-0.32	5	6
GRB2	0.026	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.004	0.1	0.17	1	-0.34	28	29
LAT	-0.01	0.083	0.15	1	-0.28	30	31
PAK2	0.009	0.12	0.28	31	-0.34	26	57
NFATC2	-0.067	0.16	-10000	0	-0.43	78	78
HRAS	0.002	0.12	0.26	18	-0.35	30	48
GAB2	0.026	0.006	-10000	0	-10000	0	0
PLA2G1B	0.017	0.089	-10000	0	-0.81	5	5
Fc epsilon R1	0.019	0.091	-10000	0	-0.22	58	58
Antigen/IgE/Fc epsilon R1	0.02	0.082	0.15	1	-0.19	58	59
mol:GDP	-0.003	0.11	0.26	3	-0.38	28	31
JUN	0.024	0.031	0.17	1	-0.31	4	5
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
FOS	-0.026	0.12	0.17	4	-0.31	78	82
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.003	0.089	0.16	2	-0.28	33	35
CHUK	0	0.11	0.26	42	-0.21	36	78
KLRG1	-0.004	0.075	0.15	4	-0.24	32	36
VAV1	-0.012	0.095	0.17	3	-0.31	34	37
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.009	0.085	0.16	3	-0.28	32	35
negative regulation of mast cell degranulation	0.001	0.099	0.18	7	-0.31	30	37
BTK	0.002	0.11	0.23	2	-0.41	20	22
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.024	0.13	-10000	0	-0.34	55	55
GAB2/PI3K/SHP2	-0.037	0.055	-10000	0	-0.21	36	36
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.009	0.088	-10000	0	-0.27	39	39
RAF1	0.017	0.094	-10000	0	-0.88	5	5
Fc epsilon R1/FcgammaRIIB/SHIP	0.034	0.12	0.25	3	-0.24	64	67
FCER1G	0.026	0.016	0.18	3	-10000	0	3
FCER1A	-0.011	0.11	-10000	0	-0.32	53	53
Antigen/IgE/Fc epsilon R1/Fyn	0.026	0.081	-10000	0	-0.18	57	57
MAPK3	0.014	0.087	-10000	0	-0.8	5	5
MAPK1	0.014	0.09	-10000	0	-0.83	5	5
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.019	0.19	-10000	0	-0.53	51	51
DUSP1	0.015	0.061	-10000	0	-0.31	17	17
NF-kappa-B/RelA	-0.001	0.054	0.12	10	-0.14	29	39
actin cytoskeleton reorganization	0	0.13	-10000	0	-0.54	14	14
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.008	0.11	0.24	4	-0.35	30	34
FER	-0.009	0.085	0.16	3	-0.3	28	31
RELA	0.026	0.006	-10000	0	-10000	0	0
ITK	0	0.061	0.17	1	-0.33	13	14
SOS1	0.026	0.005	-10000	0	-10000	0	0
PLCG1	0.005	0.13	0.27	20	-0.37	28	48
cytokine secretion	-0.005	0.035	-10000	0	-0.12	15	15
SPHK1	-0.009	0.084	0.19	3	-0.28	31	34
PTK2	-0.001	0.13	-10000	0	-0.56	14	14
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.002	0.11	-10000	0	-0.35	29	29
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.005	0.14	0.33	31	-0.34	31	62
MAP2K2	0.01	0.088	-10000	0	-0.83	5	5
MAP2K1	0.011	0.089	-10000	0	-0.82	5	5
MAP2K7	0.027	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	0.005	0.078	0.19	5	-0.25	26	31
MAP2K4	-0.035	0.25	-10000	0	-0.86	41	41
Fc epsilon R1/FcgammaRIIB	0.032	0.099	0.25	3	-0.21	59	62
mol:Choline	-0.015	0.084	0.27	21	-0.22	24	45
SHC/Grb2/SOS1	0.032	0.097	0.24	2	-0.3	21	23
FYN	0.022	0.018	-10000	0	-0.31	1	1
DOK1	0.026	0.016	-10000	0	-0.31	1	1
PXN	0.004	0.13	0.37	9	-0.52	14	23
HCLS1	-0.007	0.081	0.16	2	-0.28	30	32
PRKCB	-0.007	0.13	0.29	39	-0.28	42	81
FCGR2B	0.023	0.051	0.17	12	-0.31	9	21
IGHE	0	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	0.001	0.1	0.18	7	-0.32	30	37
LCP2	0.026	0.03	0.17	4	-0.31	3	7
PLA2G4A	-0.015	0.1	0.16	3	-0.31	38	41
RASA1	0.025	0.016	-10000	0	-0.31	1	1
mol:Phosphatidic acid	-0.015	0.084	0.27	21	-0.22	24	45
IKK complex	0.012	0.11	0.27	50	-0.18	22	72
WIPF1	0.023	0.031	-10000	0	-0.31	4	4

×

PLK1 signaling events

Figure S42. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S42. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.012	0.031	0.12	5	-0.16	13	18
BUB1B	0.015	0.035	0.16	14	-0.11	1	15
PLK1	0.015	0.029	0.1	30	-0.083	6	36
PLK1S1	0.012	0.026	0.13	7	-0.16	5	12
KIF2A	0.009	0.032	0.14	15	-0.11	1	16
regulation of mitotic centrosome separation	0.015	0.029	0.1	30	-0.082	6	36
GOLGA2	0.026	0.007	-10000	0	-10000	0	0
Hec1/SPC24	0.063	0.056	0.15	118	-0.15	4	122
WEE1	0.018	0.038	0.19	3	-0.33	3	6
cytokinesis	0.018	0.071	0.21	21	-0.2	4	25
PP2A-alpha B56	0.061	0.092	-10000	0	-0.5	11	11
AURKA	0.018	0.027	0.12	18	-0.14	1	19
PICH/PLK1	0.02	0.041	0.23	11	-0.14	2	13
CENPE	0.007	0.036	0.18	12	-0.11	1	13
RhoA/GTP	0.019	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.01	0.033	0.14	15	-0.11	1	16
PPP2CA	0.026	0.006	-10000	0	-10000	0	0
FZR1	0.026	0.005	-10000	0	-10000	0	0
TPX2	0.027	0.035	0.16	16	-0.18	1	17
PAK1	0.021	0.038	-10000	0	-0.32	6	6
SPC24	0.067	0.066	0.17	136	-10000	0	136
FBXW11	0.026	0.005	-10000	0	-10000	0	0
CLSPN	0.016	0.043	0.13	4	-0.24	9	13
GORASP1	0.026	0.004	-10000	0	-10000	0	0
metaphase	0	0.002	0.013	13	-0.013	1	14
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.007	0.017	0.057	31	-0.046	6	37
G2 phase of mitotic cell cycle	-0.001	0.002	0.01	6	-10000	0	6
STAG2	0.027	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.017	0.037	-10000	0	-0.43	3	3
spindle elongation	0.015	0.029	0.1	30	-0.082	6	36
ODF2	0.026	0.007	-10000	0	-10000	0	0
BUB1	0.036	0.096	-10000	0	-0.55	11	11
TPT1	-0.026	0.077	0.12	5	-0.17	100	105
CDC25C	0.038	0.052	0.17	15	-0.25	8	23
CDC25B	0.023	0.022	0.18	1	-0.32	1	2
SGOL1	0.012	0.031	0.16	13	-0.12	5	18
RHOA	0.026	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.041	0.033	0.25	2	-0.17	3	5
CDC14B	-0.008	0.021	-10000	0	-0.21	5	5
CDC20	0.076	0.069	0.17	163	-10000	0	163
PLK1/PBIP1	0.008	0.019	0.087	14	-0.079	3	17
mitosis	-0.003	0.003	0.025	1	-10000	0	1
FBXO5	0.009	0.03	0.14	14	-10000	0	14
CDC2	0.001	0.002	0.013	3	-0.009	14	17
NDC80	0.023	0.027	-10000	0	-0.31	3	3
metaphase plate congression	0.015	0.025	0.13	1	-0.22	3	4
ERCC6L	0.019	0.043	0.23	7	-0.18	3	10
NLP/gamma Tubulin	0.007	0.022	0.077	18	-0.067	14	32
microtubule cytoskeleton organization	-0.026	0.077	0.12	5	-0.17	100	105
G2/M transition DNA damage checkpoint	-0.001	0.002	0.011	7	-10000	0	7
PPP1R12A	0.026	0.006	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.011	7	-10000	0	7
PLK1/PRC1-2	0.081	0.069	0.17	143	-10000	0	143
GRASP65/GM130/RAB1/GTP/PLK1	0.047	0.025	0.18	1	-10000	0	1
RAB1A	0.027	0.004	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.011	0.026	0.093	31	-0.062	4	35
mitotic prometaphase	-0.001	0.002	0.018	3	-10000	0	3
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.05	0.2	10	-0.35	3	13
microtubule-based process	0.063	0.061	0.14	172	-0.088	6	178
Golgi organization	0.015	0.029	0.1	30	-0.082	6	36
Cohesin/SA2	0.027	0.022	0.11	13	-0.097	1	14
PPP1CB/MYPT1	0.038	0.009	-10000	0	-10000	0	0
KIF20A	0.077	0.071	0.17	171	-10000	0	171
APC/C/CDC20	0.063	0.061	0.14	164	-0.093	6	170
PPP2R1A	0.027	0.003	-10000	0	-10000	0	0
chromosome segregation	0.008	0.019	0.086	14	-0.078	3	17
PRC1	0.034	0.032	0.17	24	-10000	0	24
ECT2	0.024	0.066	0.23	41	-0.11	1	42
C13orf34	0.012	0.025	0.093	28	-0.07	6	34
NUDC	0.015	0.025	0.13	1	-0.22	3	4
regulation of attachment of spindle microtubules to kinetochore	0.015	0.035	0.16	14	-0.11	1	15
spindle assembly	0.01	0.024	0.093	23	-0.072	6	29
spindle stabilization	0.012	0.026	0.13	7	-0.16	5	12
APC/C/HCDH1	0.02	0.02	-10000	0	-0.17	5	5
MKLP2/PLK1	0.063	0.061	0.14	172	-0.088	6	178
CCNB1	0.031	0.031	0.18	19	-10000	0	19
PPP1CB	0.027	0.003	-10000	0	-10000	0	0
BTRC	0.026	0.007	-10000	0	-10000	0	0
ROCK2	-0.009	0.11	0.21	2	-0.35	43	45
TUBG1	0.006	0.039	0.11	4	-0.16	19	23
G2/M transition of mitotic cell cycle	0.004	0.026	0.23	1	-0.17	3	4
MLF1IP	-0.005	0.034	0.26	7	-10000	0	7
INCENP	0.026	0.004	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.059	0.33	2	-1	1	3
VDR	0.024	0.035	0.17	2	-0.31	5	7
FAM120B	0.026	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.017	0.099	-10000	0	-0.28	26	26
RXRs/LXRs/DNA/Oxysterols	-0.015	0.12	-10000	0	-0.41	24	24
MED1	0.027	0.004	-10000	0	-10000	0	0
mol:9cRA	0.001	0.011	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.021	0.032	-10000	0	-0.18	12	12
RXRs/NUR77	0.016	0.1	0.26	1	-0.18	93	94
RXRs/PPAR	-0.023	0.097	-10000	0	-0.2	101	101
NCOR2	0.026	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.024	0.12	2	-0.21	5	7
RARs/VDR/DNA/Vit D3	0.052	0.045	-10000	0	-0.17	15	15
RARA	0.027	0.004	-10000	0	-10000	0	0
NCOA1	0.027	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.035	0.17	2	-0.31	5	7
RARs/RARs/DNA/9cRA	0.038	0.037	-10000	0	-0.15	13	13
RARG	0.02	0.045	-10000	0	-0.31	9	9
RPS6KB1	0.009	0.059	0.53	5	-0.41	1	6
RARs/THRs/DNA/SMRT	0.019	0.034	-10000	0	-0.18	13	13
THRA	0.027	0.004	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.018	0.024	0.12	2	-0.21	5	7
RXRs/PPAR/9cRA/PGJ2/DNA	0.008	0.093	0.27	1	-0.16	109	110
NR1H4	-0.029	0.13	0.17	18	-0.31	85	103
RXRs/LXRs/DNA	0.027	0.11	-10000	0	-0.22	23	23
NR1H2	0.026	0.018	-10000	0	-10000	0	0
NR1H3	0.025	0.02	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.015	0.092	-10000	0	-0.16	94	94
NR4A1	0.02	0.058	0.17	9	-0.31	13	22
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.046	0.1	0.15	2	-0.19	152	154
RXRG	-0.043	0.14	0.18	6	-0.31	102	108
RXR alpha/CCPG	0.035	0.02	-10000	0	-10000	0	0
RXRA	0.024	0.019	-10000	0	-10000	0	0
RXRB	0.026	0.019	-10000	0	-10000	0	0
THRB	0.028	0.018	0.17	7	-10000	0	7
PPARG	0.01	0.075	0.17	3	-0.31	25	28
PPARD	0.027	0.004	-10000	0	-10000	0	0
TNF	-0.044	0.21	0.34	1	-0.94	24	25
mol:Oxysterols	0.001	0.01	-10000	0	-10000	0	0
cholesterol transport	-0.015	0.12	-10000	0	-0.4	24	24
PPARA	0.026	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.023	0.03	-10000	0	-0.31	4	4
RXRs/NUR77/BCL2	-0.028	0.099	-10000	0	-0.21	99	99
SREBF1	-0.018	0.1	-10000	0	-0.39	22	22
RXRs/RXRs/DNA/9cRA	0.008	0.093	0.27	1	-0.16	109	110
ABCA1	-0.021	0.11	-10000	0	-0.41	22	22
RARs/THRs	0.068	0.045	-10000	0	-0.16	13	13
RXRs/FXR	-0.017	0.12	0.26	1	-0.18	154	155
BCL2	0.016	0.052	-10000	0	-0.31	12	12

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.025	0.13	0.29	22	-0.41	23	45
FYN	0.006	0.16	0.31	26	-0.51	26	52
LAT/GRAP2/SLP76	0.013	0.13	0.26	12	-0.43	24	36
IKBKB	0.021	0.011	-10000	0	-10000	0	0
AKT1	0.013	0.13	0.31	31	-0.36	26	57
B2M	0.027	0.008	-10000	0	-10000	0	0
IKBKG	0.006	0.042	0.11	30	-0.13	14	44
MAP3K8	0.018	0.054	0.17	1	-0.31	13	14
mol:Ca2+	-0.013	0.012	0.086	2	-0.053	7	9
integrin-mediated signaling pathway	0.025	0.043	-10000	0	-0.17	21	21
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.004	0.17	0.36	22	-0.52	27	49
TRPV6	0.073	0.3	1.1	37	-10000	0	37
CD28	0.032	0.061	0.18	37	-0.31	9	46
SHC1	0.003	0.15	0.27	27	-0.49	26	53
receptor internalization	-0.009	0.15	0.26	2	-0.44	37	39
PRF1	-0.014	0.22	-10000	0	-0.88	22	22
KRAS	0.025	0.007	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
COT/AKT1	0.02	0.12	0.3	28	-0.3	25	53
LAT	-0.002	0.14	0.27	13	-0.48	26	39
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	0.026	0.059	0.18	23	-0.32	10	33
CD3E	0.022	0.053	0.18	9	-0.32	10	19
CD3G	0.009	0.089	0.18	17	-0.31	32	49
RASGRP2	0	0.037	0.082	5	-0.17	20	25
RASGRP1	0.008	0.13	0.32	28	-0.38	25	53
HLA-A	0.001	0.004	-10000	0	-10000	0	0
RASSF5	0.012	0.068	-10000	0	-0.31	21	21
RAP1A/GTP/RAPL	0.026	0.043	-10000	0	-0.17	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.079	0.22	41	-0.12	19	60
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.006	0.048	-10000	0	-0.19	21	21
PRKCA	-0.005	0.072	0.17	15	-0.23	26	41
GRAP2	0.016	0.06	0.17	2	-0.31	16	18
mol:IP3	-0.005	0.093	0.17	2	-0.33	25	27
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.008	0.13	-10000	0	-0.52	22	22
ORAI1	-0.056	0.25	0.35	16	-0.94	33	49
CSK	0	0.14	0.24	16	-0.49	25	41
B7 family/CD28	0.038	0.15	0.29	21	-0.45	25	46
CHUK	0.025	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.007	0.16	0.2	7	-0.51	30	37
PTPN6	-0.007	0.14	0.22	10	-0.5	24	34
VAV1	-0.007	0.15	0.26	9	-0.5	29	38
Monovalent TCR/CD3	-0.002	0.094	0.13	1	-0.26	43	44
CBL	0.025	0.016	-10000	0	-0.31	1	1
LCK	0.008	0.15	0.29	24	-0.53	22	46
PAG1	0.013	0.14	0.2	60	-0.51	21	81
RAP1A	0.026	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.008	0.15	0.2	7	-0.49	31	38
CD80	0.035	0.038	0.18	32	-10000	0	32
CD86	0.027	0.029	0.18	7	-0.31	2	9
PDK1/CARD11/BCL10/MALT1	0	0.061	0.1	1	-0.23	20	21
HRAS	0.028	0.017	0.17	6	-10000	0	6
GO:0035030	-0.003	0.11	0.22	9	-0.37	27	36
CD8A	0.022	0.052	0.18	6	-0.32	10	16
CD8B	0.024	0.049	0.18	9	-0.32	8	17
PTPRC	0.016	0.066	0.18	7	-0.31	18	25
PDK1/PKC theta	0.006	0.16	0.41	27	-0.46	24	51
CSK/PAG1	0.016	0.14	0.2	70	-0.5	21	91
SOS1	0.026	0.005	-10000	0	-10000	0	0
peptide-MHC class I	0.021	0.009	-10000	0	-10000	0	0
GRAP2/SLP76	0.014	0.14	0.24	5	-0.5	25	30
STIM1	-0.013	0.17	1.1	7	-0.94	5	12
RAS family/GTP	0.022	0.086	0.25	29	-0.16	28	57
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.012	0.16	0.17	1	-0.47	37	38
mol:DAG	-0.017	0.079	-10000	0	-0.3	25	25
RAP1A/GDP	0.014	0.036	0.12	27	-0.058	14	41
PLCG1	0.026	0.005	-10000	0	-10000	0	0
CD247	0.028	0.045	0.18	17	-0.32	5	22
cytotoxic T cell degranulation	-0.012	0.2	0.35	1	-0.83	22	23
RAP1A/GTP	0	0.014	-10000	0	-0.061	21	21
mol:PI-3-4-5-P3	0.008	0.14	0.31	27	-0.43	27	54
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.001	0.12	0.2	1	-0.42	25	26
NRAS	0.026	0.016	-10000	0	-0.31	1	1
ZAP70	0.04	0.053	0.17	52	-0.31	3	55
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.002	0.12	0.2	7	-0.43	25	32
MALT1	0.023	0.019	0.17	1	-0.31	1	2
TRAF6	0.026	0.005	-10000	0	-10000	0	0
CD8 heterodimer	0.035	0.059	0.26	3	-0.26	15	18
CARD11	0.021	0.046	0.17	6	-0.31	8	14
PRKCB	-0.016	0.079	0.16	7	-0.23	42	49
PRKCE	-0.001	0.067	0.17	15	-0.23	20	35
PRKCQ	-0.001	0.17	0.37	22	-0.53	25	47
LCP2	0.025	0.03	0.17	4	-0.31	3	7
BCL10	0.026	0.005	-10000	0	-10000	0	0
regulation of survival gene product expression	0.015	0.12	0.3	31	-0.3	26	57
IKK complex	0.005	0.084	0.25	32	-0.12	27	59
RAS family/GDP	0	0.01	-10000	0	-0.037	9	9
MAP3K14	0.012	0.092	0.26	27	-0.23	25	52
PDPK1	0.014	0.13	0.35	30	-0.35	24	54
TCR/CD3/MHC I/CD8/Fyn	-0.012	0.18	0.28	1	-0.63	27	28

×

Arf6 signaling events

Figure S45. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S45. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.024	0.02	-10000	0	-0.18	1	1
ARNO/beta Arrestin1-2	0.028	0.097	-10000	0	-0.75	7	7
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
EPHA2	-0.002	0.096	0.17	3	-0.31	43	46
USP6	0.025	0.008	-10000	0	-10000	0	0
IQSEC1	0.026	0.005	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.013	0.092	0.14	34	-0.23	56	90
ARRB2	0.009	0.005	-10000	0	-10000	0	0
mol:GTP	0.007	0.04	0.13	13	-0.15	6	19
ARRB1	0.025	0.016	-10000	0	-0.31	1	1
FBXO8	0.026	0.005	-10000	0	-10000	0	0
TSHR	0.019	0.057	0.17	6	-0.31	13	19
EGF	0.023	0.084	0.17	40	-0.31	23	63
somatostatin receptor activity	0	0	0.001	37	-0.001	23	60
ARAP2	0.026	0.016	-10000	0	-0.31	1	1
mol:GDP	0.009	0.089	0.21	28	-0.23	25	53
mol:PI-3-4-5-P3	0	0	0.001	34	-0.001	8	42
ITGA2B	0.02	0.048	0.17	5	-0.31	9	14
ARF6	0.027	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.066	-10000	0	-0.17	39	39
ADAP1	0.024	0.018	0.17	1	-0.31	1	2
KIF13B	0.02	0.012	-10000	0	-10000	0	0
HGF/MET	0.007	0.095	-10000	0	-0.26	50	50
PXN	0.026	0.006	-10000	0	-10000	0	0
ARF6/GTP	0.015	0.11	0.27	38	-0.22	22	60
EGFR/EGFR/EGF/EGF/ARFGEP100	0.027	0.084	-10000	0	-0.19	54	54
ADRB2	0.028	0.016	0.17	5	-10000	0	5
receptor agonist activity	0	0	0	27	0	20	47
actin filament binding	0	0	0.001	37	0	21	58
SRC	0.026	0.006	-10000	0	-10000	0	0
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
GNAQ	0.026	0.006	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	50	-0.001	13	63
ARF6/GDP	0	0.12	0.28	15	-0.32	27	42
ARF6/GDP/GULP/ACAP1	0.032	0.094	0.24	19	-0.24	15	34
alphaIIb/beta3 Integrin/paxillin/GIT1	0.014	0.093	-10000	0	-0.16	99	99
ACAP1	0.03	0.033	0.17	22	-10000	0	22
ACAP2	0.025	0.016	-10000	0	-0.31	1	1
LHCGR/beta Arrestin2	0.015	0.022	0.15	4	-10000	0	4
EFNA1	0.026	0.006	-10000	0	-10000	0	0
HGF	0.011	0.075	0.17	9	-0.31	24	33
CYTH3	-0.005	0.017	0.25	2	-10000	0	2
CYTH2	0.005	0.12	-10000	0	-0.98	7	7
NCK1	0.025	0.007	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	47	0	16	63
endosomal lumen acidification	0	0	0.001	36	0	25	61
microtubule-based process	0	0	-10000	0	0	6	6
GULP1	0.026	0.018	0.17	2	-0.31	1	3
GNAQ/ARNO	0.022	0.11	-10000	0	-0.87	7	7
mol:Phosphatidic acid	0	0	0	14	-10000	0	14
PIP3-E	0	0	0	30	0	7	37
MET	-0.004	0.093	-10000	0	-0.31	42	42
GNA14	0.025	0.016	-10000	0	-0.31	1	1
GNA15	0.012	0.068	-10000	0	-0.31	21	21
GIT1	0.027	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.001	0.001	48	-0.001	15	63
GNA11	0.016	0.058	-10000	0	-0.31	15	15
LHCGR	0.019	0.018	0.17	4	-10000	0	4
AGTR1	0.036	0.09	0.17	80	-0.31	20	100
desensitization of G-protein coupled receptor protein signaling pathway	0.015	0.022	0.15	4	-10000	0	4
IPCEF1/ARNO	0.017	0.12	-10000	0	-0.82	7	7
alphaIIb/beta3 Integrin	-0.014	0.1	0.14	2	-0.21	101	103

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.016	0.068	-10000	0	-0.21	39	39
CRKL	-0.006	0.12	0.25	11	-0.45	20	31
mol:PIP3	-0.005	0.068	-10000	0	-0.73	4	4
AKT1	-0.001	0.077	0.36	3	-0.6	4	7
PTK2B	0.019	0.012	-10000	0	-10000	0	0
RAPGEF1	0.001	0.13	0.31	19	-0.42	20	39
RANBP10	0.024	0.009	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
HGF/MET/SHIP2	0.023	0.086	-10000	0	-0.22	49	49
MAP3K5	0.004	0.13	0.31	14	-0.42	21	35
HGF/MET/CIN85/CBL/ENDOPHILINS	0.034	0.085	-10000	0	-0.2	48	48
AP1	-0.006	0.091	0.2	2	-0.21	67	69
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.026	0.006	-10000	0	-10000	0	0
apoptosis	-0.12	0.32	-10000	0	-0.76	94	94
STAT3 (dimer)	-0.023	0.1	-10000	0	-0.33	38	38
GAB1/CRKL/SHP2/PI3K	0.019	0.12	0.27	3	-0.43	20	23
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
CBL/CRK	0.008	0.13	0.32	7	-0.43	20	27
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.026	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.011	-10000	0	-10000	0	0
ELK1	0.003	0.1	0.33	37	-10000	0	37
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.007	0.066	-10000	0	-0.26	21	21
PAK1	0.001	0.085	0.41	7	-0.58	3	10
HGF/MET/RANBP10	0.019	0.085	-10000	0	-0.22	49	49
HRAS	-0.036	0.18	-10000	0	-0.53	51	51
DOCK1	-0.008	0.12	0.25	11	-0.43	21	32
GAB1	-0.007	0.12	0.26	5	-0.45	22	27
CRK	-0.006	0.12	0.28	11	-0.45	20	31
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.033	0.17	-10000	0	-0.5	54	54
JUN	0.024	0.031	0.17	1	-0.31	4	5
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.013	0.073	-10000	0	-0.22	51	51
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
cell morphogenesis	-0.011	0.15	0.34	22	-0.39	35	57
GRB2/SHC	0.018	0.081	0.17	16	-0.2	47	63
FOS	-0.026	0.12	0.17	4	-0.31	78	82
GLMN	0.003	0.001	-10000	0	-10000	0	0
cell motility	0.003	0.1	0.32	37	-10000	0	37
HGF/MET/MUC20	0.009	0.081	0.13	9	-0.22	50	59
cell migration	0.017	0.08	0.16	16	-0.2	47	63
GRB2	0.026	0.005	-10000	0	-10000	0	0
CBL	0.025	0.016	-10000	0	-0.31	1	1
MET/RANBP10	0.012	0.069	-10000	0	-0.21	42	42
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.007	0.085	-10000	0	-0.27	40	40
MET/MUC20	-0.001	0.064	-10000	0	-0.21	42	42
RAP1B	0.007	0.14	0.34	25	-0.4	20	45
RAP1A	0.003	0.13	0.31	21	-0.4	19	40
HGF/MET/RANBP9	0.023	0.087	-10000	0	-0.22	49	49
RAF1	-0.027	0.17	0.28	3	-0.51	50	53
STAT3	-0.024	0.1	-10000	0	-0.3	50	50
cell proliferation	-0.016	0.15	0.31	21	-0.39	46	67
RPS6KB1	-0.001	0.045	-10000	0	-0.25	9	9
MAPK3	-0.007	0.099	0.42	11	-10000	0	11
MAPK1	-0.001	0.12	0.49	16	-10000	0	16
RANBP9	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.002	0.14	0.32	11	-0.42	31	42
SRC	-0.021	0.081	-10000	0	-0.26	38	38
PI3K	0.016	0.086	0.17	14	-0.22	46	60
MET/Glomulin	0.015	0.029	-10000	0	-0.12	14	14
SOS1	0.026	0.005	-10000	0	-10000	0	0
MAP2K1	-0.02	0.17	0.31	10	-0.47	50	60
MET	-0.004	0.093	-10000	0	-0.31	42	42
MAP4K1	0.004	0.13	0.31	9	-0.44	21	30
PTK2	0.022	0.011	-10000	0	-10000	0	0
MAP2K2	-0.02	0.17	0.32	12	-0.47	50	62
BAD	0.001	0.082	0.42	5	-0.64	3	8
MAP2K4	0.002	0.12	0.29	14	-0.38	21	35
SHP2/GRB2/SOS1/GAB1	0.005	0.12	-10000	0	-0.35	38	38
INPPL1	0.026	0.005	-10000	0	-10000	0	0
PXN	0.026	0.006	-10000	0	-10000	0	0
SH3KBP1	0.027	0.003	-10000	0	-10000	0	0
HGS	-0.016	0.067	-10000	0	-0.21	48	48
PLCgamma1/PKC	0.019	0.004	-10000	0	-10000	0	0
HGF	0.011	0.075	0.17	9	-0.31	24	33
RASA1	0.025	0.016	-10000	0	-0.31	1	1
NCK1	0.025	0.007	-10000	0	-10000	0	0
PTPRJ	0.026	0.006	-10000	0	-10000	0	0
NCK/PLCgamma1	0.019	0.085	0.17	17	-0.21	46	63
PDPK1	-0.001	0.075	-10000	0	-0.63	4	4
HGF/MET/SHIP	0.015	0.11	-10000	0	-0.25	56	56

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.11	0.42	-10000	0	-1.2	33	33
STAT6 (cleaved dimer)	-0.14	0.44	-10000	0	-1.2	48	48
IGHG1	-0.009	0.17	-10000	0	-0.46	8	8
IGHG3	-0.11	0.4	-10000	0	-1.1	42	42
AKT1	-0.055	0.27	-10000	0	-0.71	38	38
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.035	0.24	-10000	0	-0.71	24	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.048	0.28	-10000	0	-0.78	26	26
THY1	-0.11	0.42	-10000	0	-1.2	33	33
MYB	0.033	0.031	0.17	23	-10000	0	23
HMGA1	0.027	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.077	0.34	-10000	0	-0.85	49	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.054	0.29	-10000	0	-0.79	34	34
SP1	0.03	0.01	-10000	0	-0.093	2	2
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
SOCS5	0.01	0.037	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.13	0.44	-10000	0	-1.2	46	46
SOCS1	-0.073	0.3	-10000	0	-0.74	41	41
SOCS3	-0.14	0.45	-10000	0	-1.2	70	70
FCER2	-0.088	0.38	-10000	0	-1.1	42	42
PARP14	0.026	0.011	-10000	0	-10000	0	0
CCL17	-0.11	0.42	-10000	0	-1.2	35	35
GRB2	0.026	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.035	0.24	0.38	1	-0.64	34	35
T cell proliferation	-0.12	0.43	-10000	0	-1.2	38	38
IL4R/JAK1	-0.12	0.42	-10000	0	-1.2	36	36
EGR2	-0.12	0.46	-10000	0	-1.4	38	38
JAK2	0.011	0.056	-10000	0	-0.34	1	1
JAK3	0.021	0.041	0.18	11	-0.29	3	14
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
JAK1	0.015	0.032	-10000	0	-10000	0	0
COL1A2	-0.001	0.18	-10000	0	-1.2	3	3
CCL26	-0.096	0.42	-10000	0	-1.2	33	33
IL4R	-0.12	0.44	-10000	0	-1.3	35	35
PTPN6	0.012	0.028	-10000	0	-10000	0	0
IL13RA2	-0.2	0.55	-10000	0	-1.3	76	76
IL13RA1	0.012	0.054	-10000	0	-10000	0	0
IRF4	-0.054	0.34	-10000	0	-1.2	32	32
ARG1	0.002	0.15	-10000	0	-0.53	7	7
CBL	-0.073	0.31	-10000	0	-0.79	49	49
GTF3A	0.031	0.009	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
IL13RA1/JAK2	0.025	0.078	-10000	0	-0.24	1	1
IRF4/BCL6	-0.048	0.31	-10000	0	-1.1	31	31
CD40LG	0.018	0.085	0.19	22	-0.24	37	59
MAPK14	-0.098	0.36	-10000	0	-0.88	62	62
mitosis	-0.05	0.26	0.4	1	-0.66	38	39
STAT6	-0.13	0.49	-10000	0	-1.4	38	38
SPI1	0.03	0.022	0.18	4	-0.31	1	5
RPS6KB1	-0.049	0.25	0.39	1	-0.64	37	38
STAT6 (dimer)	-0.13	0.49	-10000	0	-1.4	38	38
STAT6 (dimer)/PARP14	-0.12	0.44	-10000	0	-1.3	36	36
mast cell activation	0	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.076	0.29	-10000	0	-0.74	43	43
FRAP1	-0.055	0.27	-10000	0	-0.71	38	38
LTA	-0.11	0.42	-10000	0	-1.2	37	37
FES	0.023	0.034	-10000	0	-0.31	5	5
T-helper 1 cell differentiation	0.12	0.47	1.3	40	-10000	0	40
CCL11	-0.11	0.4	-10000	0	-1.2	34	34
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.041	0.27	-10000	0	-0.76	28	28
IL2RG	0.021	0.048	0.18	15	-0.3	5	20
IL10	-0.13	0.46	-10000	0	-1.3	45	45
IRS1	0.017	0.058	-10000	0	-0.31	15	15
IRS2	0.026	0.02	0.17	3	-0.31	1	4
IL4	-0.01	0.17	-10000	0	-0.9	8	8
IL5	-0.11	0.42	-10000	0	-1.2	36	36
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.073	0.35	-10000	0	-0.92	33	33
COL1A1	0	0.18	-10000	0	-1.2	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.12	0.43	-10000	0	-1.3	32	32
IL2R gamma/JAK3	0.033	0.059	0.22	15	-0.24	7	22
TFF3	-0.1	0.42	-10000	0	-1.2	34	34
ALOX15	-0.13	0.48	-10000	0	-1.3	52	52
MYBL1	0.021	0.018	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.1	0.37	-10000	0	-1	39	39
SHC1	0.026	0.006	-10000	0	-10000	0	0
CEBPB	0.03	0.008	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.043	0.26	-10000	0	-0.83	18	18
mol:PI-3-4-5-P3	-0.055	0.28	-10000	0	-0.71	38	38
PI3K	-0.061	0.29	-10000	0	-0.76	38	38
DOK2	0.019	0.023	0.17	3	-0.31	1	4
ETS1	0.002	0.043	0.15	1	-0.27	4	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.028	0.22	0.35	2	-0.58	29	31
ITGB3	-0.24	0.6	-10000	0	-1.3	104	104
PIGR	-0.24	0.61	-10000	0	-1.3	108	108
IGHE	-0.006	0.061	0.18	15	-0.13	6	21
MAPKKK cascade	-0.027	0.21	0.35	2	-0.57	29	31
BCL6	0.025	0.007	-10000	0	-10000	0	0
OPRM1	-0.12	0.41	-10000	0	-1.2	35	35
RETNLB	-0.11	0.42	-10000	0	-1.2	33	33
SELP	-0.12	0.44	-10000	0	-1.3	38	38
AICDA	-0.11	0.4	-10000	0	-1.2	33	33

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.01	0.36	0.66	1	-1.1	27	28
PLK1	0.05	0.05	-10000	0	-0.51	1	1
BIRC5	0.039	0.12	-10000	0	-0.75	8	8
HSPA1B	0.01	0.36	0.63	1	-1.1	27	28
MAP2K1	0.029	0.046	-10000	0	-10000	0	0
BRCA2	-0.009	0.4	-10000	0	-1.2	39	39
FOXM1	-0.01	0.46	-10000	0	-1.5	30	30
XRCC1	0.007	0.36	-10000	0	-1.1	27	27
FOXM1B/p19	-0.033	0.41	-10000	0	-1.3	32	32
Cyclin D1/CDK4	0.014	0.34	-10000	0	-1	28	28
CDC2	0.007	0.38	-10000	0	-1.2	29	29
TGFA	-0.004	0.36	-10000	0	-1	36	36
SKP2	0.005	0.38	0.64	4	-1.2	31	35
CCNE1	0.027	0.024	0.18	5	-10000	0	5
CKS1B	0.009	0.36	-10000	0	-1.1	31	31
RB1	-0.005	0.27	-10000	0	-0.88	28	28
FOXM1C/SP1	0	0.41	-10000	0	-1.3	30	30
AURKB	-0.038	0.28	-10000	0	-0.84	48	48
CENPF	0.016	0.37	0.66	1	-1.1	27	28
CDK4	0.023	0.026	-10000	0	-10000	0	0
MYC	0	0.31	0.56	1	-0.91	30	31
CHEK2	0.029	0.045	-10000	0	-0.14	1	1
ONECUT1	0.006	0.36	-10000	0	-1.1	31	31
CDKN2A	0.046	0.064	0.17	100	-10000	0	100
LAMA4	0.004	0.38	-10000	0	-1.2	29	29
FOXM1B/HNF6	-0.011	0.42	-10000	0	-1.3	31	31
FOS	-0.095	0.51	-10000	0	-1.1	86	86
SP1	0.028	0.006	-10000	0	-10000	0	0
CDC25B	0.008	0.36	-10000	0	-1.1	27	27
response to radiation	0.011	0.025	-10000	0	-10000	0	0
CENPB	0.008	0.36	-10000	0	-1.1	27	27
CENPA	0.014	0.36	-10000	0	-1.1	27	27
NEK2	0.017	0.37	-10000	0	-1.1	27	27
HIST1H2BA	0.005	0.36	-10000	0	-1.1	27	27
CCNA2	0.048	0.058	0.18	74	-10000	0	74
EP300	0.025	0.026	-10000	0	-0.31	3	3
CCNB1/CDK1	-0.006	0.42	-10000	0	-1.4	27	27
CCNB2	0.01	0.36	0.66	1	-1.1	27	28
CCNB1	0.007	0.38	-10000	0	-1.2	27	27
ETV5	-0.011	0.43	0.67	1	-1.2	41	42
ESR1	-0.006	0.39	0.66	1	-1.2	34	35
CCND1	0.002	0.34	-10000	0	-1.1	28	28
GSK3A	0.028	0.04	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.067	0.065	0.2	43	-10000	0	43
CDK2	0.024	0.019	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.012	0.03	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.006	0.39	-10000	0	-1.2	30	30
GAS1	-0.039	0.47	0.65	3	-1.2	57	60
MMP2	0.002	0.38	0.66	1	-1.2	30	31
RB1/FOXM1C	-0.023	0.36	-10000	0	-1.1	30	30
CREBBP	0.026	0.005	-10000	0	-10000	0	0

×

IL12-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.017	0.083	0.21	5	-0.29	12	17
TBX21	-0.033	0.3	-10000	0	-0.93	34	34
B2M	0.026	0.014	-10000	0	-10000	0	0
TYK2	0.02	0.032	-10000	0	-10000	0	0
IL12RB1	0.022	0.061	0.2	18	-0.34	6	24
GADD45B	-0.011	0.26	-10000	0	-0.86	26	26
IL12RB2	0.011	0.069	0.2	5	-0.31	16	21
GADD45G	-0.003	0.25	-10000	0	-0.85	24	24
natural killer cell activation	0.003	0.016	0.045	6	-0.04	18	24
RELB	0.027	0.004	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
IL18	0.018	0.055	-10000	0	-0.31	12	12
IL2RA	0.045	0.064	0.17	76	-0.31	5	81
IFNG	0.033	0.037	0.17	31	-10000	0	31
STAT3 (dimer)	-0.014	0.24	-10000	0	-0.69	36	36
HLA-DRB5	-0.003	0.008	-10000	0	-0.023	64	64
FASLG	-0.037	0.31	-10000	0	-1.1	29	29
NF kappa B2 p52/RelB	-0.02	0.28	-10000	0	-0.85	34	34
CD4	0.018	0.034	0.18	5	-0.31	2	7
SOCS1	0.026	0.02	0.17	3	-0.31	1	4
EntrezGene:6955	-0.003	0.012	-10000	0	-0.028	81	81
CD3D	0.017	0.064	0.18	23	-0.32	10	33
CD3E	0.013	0.057	0.18	9	-0.32	10	19
CD3G	0.001	0.092	0.18	17	-0.32	32	49
IL12Rbeta2/JAK2	0.026	0.066	0.19	4	-0.22	17	21
CCL3	-0.038	0.31	-10000	0	-1	30	30
CCL4	-0.031	0.29	-10000	0	-0.94	29	29
HLA-A	0	0.007	-10000	0	-0.045	12	12
IL18/IL18R	0.057	0.08	0.2	12	-0.21	27	39
NOS2	-0.052	0.36	-10000	0	-1.1	41	41
IL12/IL12R/TYK2/JAK2/SPHK2	0.018	0.082	0.2	5	-0.26	13	18
IL1R1	-0.031	0.28	-10000	0	-0.92	29	29
IL4	-0.008	0.031	-10000	0	-10000	0	0
JAK2	0.02	0.035	-10000	0	-0.32	1	1
EntrezGene:6957	-0.003	0.011	-10000	0	-0.027	70	70
TCR/CD3/MHC I/CD8	-0.032	0.2	-10000	0	-0.66	34	34
RAB7A	0.019	0.22	0.52	2	-0.7	23	25
lysosomal transport	0.021	0.22	0.45	5	-0.66	23	28
FOS	-0.17	0.48	-10000	0	-1.2	90	90
STAT4 (dimer)	0.012	0.25	0.38	1	-0.72	33	34
STAT5A (dimer)	-0.015	0.28	0.4	1	-0.81	37	38
GZMA	-0.034	0.29	0.52	1	-0.94	32	33
GZMB	-0.05	0.33	-10000	0	-1.1	36	36
HLX	0.031	0.027	0.17	16	-10000	0	16
LCK	-0.036	0.3	0.48	1	-0.87	38	39
TCR/CD3/MHC II/CD4	-0.038	0.13	-10000	0	-0.28	85	85
IL2/IL2R	0.065	0.084	0.3	14	-0.21	24	38
MAPK14	0.001	0.26	-10000	0	-0.85	26	26
CCR5	-0.014	0.27	-10000	0	-0.97	22	22
IL1B	-0.004	0.12	0.19	22	-0.33	49	71
STAT6	0.015	0.092	-10000	0	-0.41	3	3
STAT4	0.028	0.039	0.17	13	-0.31	4	17
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT1	0.029	0.019	0.17	8	-10000	0	8
NFKB1	0.027	0.004	-10000	0	-10000	0	0
NFKB2	0.026	0.013	0.17	3	-10000	0	3
IL12B	0.029	0.051	0.19	30	-10000	0	30
CD8A	0.021	0.053	0.18	6	-0.31	10	16
CD8B	0.023	0.049	0.18	9	-0.31	8	17
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.017	0.083	0.29	12	-0.21	5	17
IL2RB	0.014	0.072	0.17	7	-0.31	22	29
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.23	0.37	3	-0.66	33	36
IL2RG	0.028	0.042	0.17	15	-0.31	5	20
IL12	0.035	0.067	0.21	17	-0.22	8	25
STAT5A	0.026	0.005	-10000	0	-10000	0	0
CD247	0.019	0.051	0.18	17	-0.32	5	22
IL2	0.022	0.012	0.17	2	-10000	0	2
SPHK2	0.027	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.015	0.056	0.19	5	-0.31	8	13
IL12/IL12R/TYK2/JAK2	-0.034	0.32	-10000	0	-0.93	38	38
MAP2K3	-0.005	0.26	-10000	0	-0.86	27	27
RIPK2	0.021	0.011	-10000	0	-10000	0	0
MAP2K6	-0.003	0.26	-10000	0	-0.82	30	30
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.003	0.009	-10000	0	-0.025	74	74
IL18RAP	0.021	0.067	0.18	16	-0.31	15	31
IL12Rbeta1/TYK2	0.033	0.059	0.18	15	-0.26	6	21
EOMES	-0.025	0.21	-10000	0	-1.1	18	18
STAT1 (dimer)	0.006	0.24	0.42	3	-0.68	35	38
T cell proliferation	0.012	0.2	0.33	2	-0.54	36	38
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.023	0.041	-10000	0	-0.31	6	6
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.004	0.21	-10000	0	-0.62	27	27
ATF2	-0.004	0.24	0.42	1	-0.79	26	27

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.055	0.051	-10000	0	-0.17	19	19
ER alpha/Gai/GDP/Gbeta gamma	-0.049	0.16	0.2	1	-0.4	58	59
AKT1	-0.022	0.18	-10000	0	-0.7	29	29
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.017	0.18	-10000	0	-0.7	29	29
mol:Ca2+	-0.005	0.054	0.17	1	-0.33	6	7
IGF1R	0.026	0.017	0.17	1	-0.31	1	2
E2/ER alpha (dimer)/Striatin	0.013	0.068	0.13	1	-0.19	47	48
SHC1	0.026	0.006	-10000	0	-10000	0	0
apoptosis	0.02	0.17	0.66	29	-10000	0	29
RhoA/GTP	0.019	0.03	-10000	0	-0.15	14	14
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.016	0.13	0.24	1	-0.35	45	46
regulation of stress fiber formation	0.023	0.066	0.25	7	-0.17	27	34
E2/ERA-ERB (dimer)	0.032	0.042	0.13	20	-0.18	15	35
KRAS	0.025	0.007	-10000	0	-10000	0	0
G13/GTP	0.027	0.034	0.12	1	-0.16	15	16
pseudopodium formation	-0.023	0.066	0.17	27	-0.25	7	34
E2/ER alpha (dimer)/PELP1	0.027	0.038	0.13	1	-0.17	16	17
GRB2	0.026	0.005	-10000	0	-10000	0	0
GNG2	0.023	0.037	-10000	0	-0.31	6	6
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
HRAS	0.028	0.017	0.17	6	-10000	0	6
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.022	0.14	0.33	2	-0.44	28	30
E2/ER beta (dimer)	0.024	0.02	0.12	19	-10000	0	19
mol:GDP	0.009	0.058	0.16	1	-0.25	20	21
mol:NADP	-0.022	0.14	0.33	2	-0.44	28	30
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:IP3	-0.006	0.055	-10000	0	-0.34	6	6
IGF-1R heterotetramer	0.026	0.017	0.17	1	-0.31	1	2
PLCB1	0	0.058	-10000	0	-0.35	6	6
PLCB2	0.001	0.057	-10000	0	-0.33	6	6
IGF1	0.008	0.089	0.17	17	-0.31	33	50
mol:L-citrulline	-0.022	0.14	0.33	2	-0.44	28	30
RHOA	0.026	0.005	-10000	0	-10000	0	0
Gai/GDP	-0.13	0.29	-10000	0	-0.62	123	123
JNK cascade	0.023	0.02	0.12	19	-10000	0	19
BCAR1	0.022	0.011	-10000	0	-10000	0	0
ESR2	0.032	0.029	0.17	19	-10000	0	19
GNAQ	0.026	0.006	-10000	0	-10000	0	0
ESR1	0.016	0.06	0.17	1	-0.31	16	17
Gq family/GDP/Gbeta gamma	-0.018	0.15	-10000	0	-0.44	48	48
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.015	0.073	-10000	0	-0.46	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.018	0.14	0.24	1	-0.34	49	50
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
E2/ER alpha (dimer)	0.012	0.041	0.12	1	-0.21	16	17
STRN	0.002	0.087	-10000	0	-0.31	36	36
GNAL	-0.054	0.14	-10000	0	-0.31	117	117
PELP1	0.025	0.008	-10000	0	-10000	0	0
MAPK11	0.01	0.014	-10000	0	-10000	0	0
GNAI2	0.026	0.005	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
HBEGF	-0.047	0.16	0.38	6	-0.39	53	59
cAMP biosynthetic process	-0.012	0.081	-10000	0	-0.15	119	119
SRC	-0.049	0.15	0.2	2	-0.39	56	58
PI3K	0.031	0.034	-10000	0	-0.24	6	6
GNB1	0.027	0.004	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.038	0.065	-10000	0	-0.28	14	14
SOS1	0.026	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.037	0.12	-10000	0	-0.3	58	58
Gs family/GTP	-0.007	0.086	-10000	0	-0.15	119	119
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.019	-10000	0	-10000	0	0
vasodilation	-0.02	0.13	0.29	3	-0.42	28	31
mol:DAG	-0.006	0.055	-10000	0	-0.34	6	6
Gs family/GDP/Gbeta gamma	-0.017	0.088	-10000	0	-0.29	23	23
MSN	-0.024	0.068	0.18	27	-0.26	7	34
Gq family/GTP	0.007	0.062	-10000	0	-0.34	6	6
mol:PI-3-4-5-P3	-0.016	0.17	-10000	0	-0.68	29	29
NRAS	0.026	0.016	-10000	0	-0.31	1	1
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.02	0.13	0.42	28	-0.29	3	31
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.024	0.062	0.16	1	-0.24	20	21
NOS3	-0.023	0.14	0.33	2	-0.46	28	30
GNA11	0.016	0.058	-10000	0	-0.31	15	15
MAPKKK cascade	-0.035	0.16	0.36	2	-0.48	35	37
E2/ER alpha (dimer)/PELP1/Src	-0.02	0.14	0.27	3	-0.36	50	53
ruffle organization	-0.023	0.066	0.17	27	-0.25	7	34
ROCK2	-0.02	0.069	0.19	27	-0.26	4	31
GNA14	0.025	0.016	-10000	0	-0.31	1	1
GNA15	0.012	0.068	-10000	0	-0.31	21	21
GNA13	0.026	0.005	-10000	0	-10000	0	0
MMP9	-0.058	0.15	0.38	4	-0.38	56	60
MMP2	-0.04	0.15	0.26	3	-0.39	55	58

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.028	0.054	-10000	0	-0.15	38	38
RGS9BP	0.026	0.022	0.17	1	-0.31	2	3
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.02	0.015	0.17	4	-10000	0	4
mol:Na +	0.026	0.025	0.13	20	-10000	0	20
mol:ADP	-0.016	0.007	-10000	0	-10000	0	0
GNAT2	0.026	0.014	0.17	4	-10000	0	4
RGS9-1/Gbeta5/R9AP	0.005	0.095	-10000	0	-0.18	100	100
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.029	0.018	0.14	7	-10000	0	7
GRK7	0.021	0.007	-10000	0	-10000	0	0
CNGB3	0.019	0.024	0.17	10	-10000	0	10
Cone Metarhodopsin II/X-Arrestin	0.016	0.006	0.12	1	-10000	0	1
mol:Ca2+	0.03	0.086	0.19	98	-10000	0	98
Cone PDE6	0.018	0.09	-10000	0	-0.16	94	94
Cone Metarhodopsin II	0.025	0.013	0.12	4	-10000	0	4
Na + (4 Units)	0.042	0.039	0.24	3	-10000	0	3
GNAT2/GDP	0.017	0.088	-10000	0	-0.15	99	99
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.011	0.029	0.18	11	-10000	0	11
Cone Transducin	0.03	0.058	-10000	0	-0.16	38	38
SLC24A2	0.036	0.043	0.17	44	-10000	0	44
GNB3/GNGT2	0.017	0.068	0.14	1	-0.21	38	39
GNB3	0.003	0.084	-10000	0	-0.31	33	33
GNAT2/GTP	0.019	0.01	0.12	4	-10000	0	4
CNGA3	0.027	0.027	0.17	15	-10000	0	15
ARR3	0.021	0.008	0.17	1	-10000	0	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.027	0.026	0.13	20	-10000	0	20
mol:Pi	0.005	0.095	-10000	0	-0.18	100	100
Cone CNG Channel	0.039	0.033	0.23	1	-10000	0	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.036	0.043	0.17	44	-10000	0	44
RGS9	-0.041	0.14	0.17	3	-0.31	100	103
PDE6C	0.018	0.007	-10000	0	-10000	0	0
GNGT2	0.023	0.034	0.17	1	-0.31	5	6
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.019	0.016	0.17	4	-10000	0	4

×

Regulation of p38-alpha and p38-beta

Figure S52. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S52. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.035	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.026	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.034	0.17	10	-0.31	3	13
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.025	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.045	0.084	-10000	0	-0.16	161	161
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
FYN	0.022	0.018	-10000	0	-0.31	1	1
MAP3K12	0.022	0.037	-10000	0	-0.31	6	6
FGR	0.026	0.022	0.17	1	-0.31	2	3
p38 alpha/TAB1	-0.043	0.078	-10000	0	-0.24	50	50
PRKG1	-0.062	0.15	-10000	0	-0.31	129	129
DUSP8	0.028	0.015	0.17	5	-10000	0	5
PGK/cGMP/p38 alpha	-0.045	0.12	0.17	2	-0.27	77	79
apoptosis	-0.042	0.075	-10000	0	-0.23	50	50
RAL/GTP	0.032	0.013	-10000	0	-10000	0	0
LYN	0.023	0.01	-10000	0	-10000	0	0
DUSP1	0.015	0.061	-10000	0	-0.31	17	17
PAK1	0.022	0.037	-10000	0	-0.31	6	6
SRC	0.026	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.06	0.025	-10000	0	-10000	0	0
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.025	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.033	0.011	-10000	0	-10000	0	0
MAPK11	-0.023	0.12	0.24	24	-0.27	53	77
BLK	0	0.1	0.17	32	-0.31	43	75
HCK	0.024	0.031	0.17	1	-0.31	4	5
MAP2K3	0.026	0.005	-10000	0	-10000	0	0
DUSP16	0.024	0.009	-10000	0	-10000	0	0
DUSP10	0.026	0.006	-10000	0	-10000	0	0
TRAF6/MEKK3	0.033	0.008	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.013	0.11	0.23	21	-0.27	42	63
positive regulation of innate immune response	-0.023	0.14	0.28	21	-0.32	48	69
LCK	0.03	0.02	0.17	9	-10000	0	9
p38alpha-beta/MKP7	-0.012	0.14	0.3	16	-0.31	46	62
p38alpha-beta/MKP5	-0.015	0.14	0.3	14	-0.31	46	60
PGK/cGMP	-0.041	0.1	-10000	0	-0.21	129	129
PAK2	0.025	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.02	0.14	0.3	14	-0.31	51	65
CDC42	0.027	0.003	-10000	0	-10000	0	0
RALB	0.026	0.006	-10000	0	-10000	0	0
RALA	0.024	0.008	-10000	0	-10000	0	0
PAK3	-0.098	0.16	-10000	0	-0.31	183	183

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.009	0.098	-10000	0	-0.21	92	92
AKT1	-0.013	0.15	0.35	8	-0.42	41	49
PTK2B	-0.046	0.11	0.17	4	-0.48	24	28
VEGFR2 homodimer/Frs2	0.008	0.11	-10000	0	-0.49	21	21
CAV1	-0.013	0.1	-10000	0	-0.31	55	55
CALM1	0.026	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.015	0.11	-10000	0	-0.31	43	43
endothelial cell proliferation	-0.02	0.16	0.32	18	-0.46	31	49
mol:Ca2+	-0.014	0.11	0.18	6	-0.47	21	27
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.026	0.11	-10000	0	-0.3	40	40
RP11-342D11.1	-0.032	0.1	0.17	7	-0.46	22	29
CDH5	0.024	0.009	-10000	0	-10000	0	0
VEGFA homodimer	0.051	0.056	-10000	0	-0.16	27	27
SHC1	0.026	0.006	-10000	0	-10000	0	0
SHC2	0.029	0.031	0.17	11	-0.31	2	13
HRAS/GDP	0.016	0.1	-10000	0	-0.41	22	22
SH2D2A	0.03	0.041	0.17	22	-0.31	3	25
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.019	0.12	0.28	2	-0.43	22	24
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.017	0.12	-10000	0	-0.32	43	43
VEGFR1 homodimer	0.024	0.028	0.17	2	-0.31	3	5
SHC/GRB2/SOS1	0.037	0.12	-10000	0	-0.44	22	22
GRB10	-0.014	0.1	0.18	3	-0.47	20	23
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
GRB2	0.026	0.005	-10000	0	-10000	0	0
PAK1	0.022	0.037	-10000	0	-0.31	6	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.035	0.11	-10000	0	-0.44	21	21
HRAS	0.028	0.017	0.17	6	-10000	0	6
VEGF/Rho/ROCK1/Integrin Complex	-0.039	0.13	-10000	0	-0.4	34	34
HIF1A	0.026	0.016	-10000	0	-0.31	1	1
FRS2	0.026	0.006	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.025	0.11	-10000	0	-0.3	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.025	0.023	0.17	1	-0.31	2	3
Nck/Pak	0.033	0.03	-10000	0	-0.21	6	6
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.01	0.11	-10000	0	-0.34	38	38
mol:GDP	0.025	0.11	-10000	0	-0.43	22	22
mol:NADP	0.006	0.11	0.35	12	-0.37	22	34
eNOS/Hsp90	0.013	0.1	0.3	6	-0.35	22	28
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:IP3	-0.014	0.11	0.18	6	-0.48	21	27
HIF1A/ARNT	0.037	0.016	-10000	0	-0.21	1	1
SHB	0.024	0.026	-10000	0	-0.31	3	3
VEGFA	0.011	0.077	0.18	5	-0.31	26	31
VEGFC	0.026	0.017	0.17	1	-0.31	1	2
FAK1/Vinculin	-0.05	0.18	0.26	4	-0.48	51	55
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.007	0.14	-10000	0	-0.24	99	99
PTPN6	0.025	0.007	-10000	0	-10000	0	0
EPAS1	0.017	0.071	0.18	1	-0.31	21	22
mol:L-citrulline	0.006	0.11	0.35	12	-0.37	22	34
ITGAV	0.026	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.028	0.11	-10000	0	-0.44	21	21
VEGFR2 homodimer/VEGFA homodimer	0.016	0.12	-10000	0	-0.33	44	44
VEGFR2/3 heterodimer	0.007	0.11	-10000	0	-0.49	22	22
VEGFB	0.026	0.005	-10000	0	-10000	0	0
MAPK11	-0.029	0.11	0.23	4	-0.46	24	28
VEGFR2 homodimer	-0.009	0.12	-10000	0	-0.57	21	21
FLT1	0.025	0.028	0.17	2	-0.31	3	5
NEDD4	0.022	0.045	-10000	0	-0.31	9	9
MAPK3	-0.045	0.11	0.23	7	-0.46	25	32
MAPK1	-0.044	0.12	0.24	8	-0.46	25	33
VEGFA145/NRP2	0.011	0.084	0.14	4	-0.22	56	60
VEGFR1/2 heterodimer	0.007	0.11	-10000	0	-0.52	21	21
KDR	-0.009	0.12	-10000	0	-0.57	21	21
VEGFA165/NRP1/VEGFR2 homodimer	0.007	0.13	-10000	0	-0.49	25	25
SRC	0.026	0.006	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.04	0.12	0.23	13	-0.47	25	38
PI3K	-0.011	0.14	-10000	0	-0.42	42	42
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.013	0.11	-10000	0	-0.31	43	43
FES	-0.015	0.11	0.18	7	-0.49	22	29
GAB1	-0.01	0.14	-10000	0	-0.41	43	43
VEGFR2 homodimer/VEGFA homodimer/Src	0.014	0.12	-10000	0	-0.32	43	43
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
SOS1	0.026	0.005	-10000	0	-10000	0	0
ARNT	0.026	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.002	0.11	0.37	3	-0.42	22	25
VEGFR2 homodimer/VEGFA homodimer/Yes	0.014	0.11	-10000	0	-0.32	41	41
PI3K/GAB1	-0.011	0.15	-10000	0	-0.44	42	42
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.034	0.12	-10000	0	-0.47	19	19
PRKACA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.022	0.11	-10000	0	-0.46	22	22
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
CDC42	-0.015	0.11	0.18	7	-0.47	22	29
actin cytoskeleton reorganization	0.016	0.12	-10000	0	-0.31	43	43
PTK2	-0.056	0.17	-10000	0	-0.53	41	41
EDG1	-0.032	0.1	0.17	7	-0.46	22	29
mol:DAG	-0.014	0.11	0.18	6	-0.48	21	27
CaM/Ca2+	0	0.1	-10000	0	-0.44	21	21
MAP2K3	-0.039	0.1	0.17	6	-0.44	24	30
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.026	0.12	-10000	0	-0.48	20	20
PLCG1	-0.015	0.11	0.18	6	-0.48	21	27
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.027	0.11	-10000	0	-0.44	21	21
IQGAP1	0.027	0.003	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.013	0.12	-10000	0	-0.32	42	42
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.013	0.11	-10000	0	-0.31	43	43
cell migration	-0.045	0.17	0.24	5	-0.47	47	52
mol:PI-3-4-5-P3	-0.009	0.13	-10000	0	-0.39	42	42
FYN	0.022	0.018	-10000	0	-0.31	1	1
VEGFB/NRP1	-0.007	0.1	0.18	6	-0.45	21	27
mol:NO	0.006	0.11	0.35	12	-0.37	22	34
PXN	0.026	0.006	-10000	0	-10000	0	0
HRAS/GTP	0	0.098	-10000	0	-0.41	22	22
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.007	0.11	-10000	0	-0.48	20	20
VHL	0.025	0.016	-10000	0	-0.31	1	1
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
NOS3	0.005	0.12	0.36	12	-0.42	22	34
VEGFR2 homodimer/VEGFA homodimer/Sck	0.015	0.12	-10000	0	-0.32	43	43
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.039	0.11	0.22	7	-0.48	21	28
PRKCB	-0.06	0.12	0.17	5	-0.51	24	29
VCL	0.01	0.072	-10000	0	-0.31	24	24
VEGFA165/NRP1	-0.002	0.11	0.18	7	-0.46	22	29
VEGFR1/2 heterodimer/VEGFA homodimer	0.014	0.12	0.24	1	-0.34	40	41
VEGFA165/NRP2	0.011	0.084	0.14	4	-0.22	56	60
MAPKKK cascade	0.004	0.1	0.34	3	-0.42	20	23
NRP2	0.005	0.083	-10000	0	-0.31	32	32
VEGFC homodimer	0.026	0.017	0.17	1	-0.31	1	2
NCK1	0.025	0.007	-10000	0	-10000	0	0
ROCK1	0.025	0.016	-10000	0	-0.31	1	1
FAK1/Paxillin	-0.046	0.17	0.3	3	-0.5	43	46
MAP3K13	-0.019	0.11	0.18	4	-0.47	24	28
PDPK1	-0.02	0.11	0.25	1	-0.36	41	42

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.003	0.087	-10000	0	-0.16	115	115
MAPK9	0.006	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.008	0.013	0.25	1	-10000	0	1
GNB1/GNG2	0.033	0.024	-10000	0	-0.18	6	6
GNB1	0.027	0.004	-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	0.006	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.024	0.073	-10000	0	-0.15	117	117
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	0.012	0.019	0.045	117	-10000	0	117
GNAL	-0.054	0.14	-10000	0	-0.31	117	117
GNG2	0.023	0.037	-10000	0	-0.31	6	6
CRH	0.015	0.013	0.17	2	-10000	0	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0.038	-10000	0	-0.24	12	12
MAPK11	0.007	0.004	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.01	0.14	-10000	0	-0.5	31	31
HDAC1	0.024	0.004	-10000	0	-10000	0	0
AES	0.026	0.005	-10000	0	-10000	0	0
FBXW11	0.026	0.005	-10000	0	-10000	0	0
DTX1	0.031	0.032	0.17	18	-0.31	1	19
LRP6/FZD1	0.032	0.02	-10000	0	-0.21	1	1
TLE1	0.025	0.006	-10000	0	-10000	0	0
AP1	-0.026	0.1	-10000	0	-0.24	76	76
NCSTN	0.026	0.006	-10000	0	-10000	0	0
ADAM10	0.012	0.068	-10000	0	-0.31	21	21
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.042	0.039	-10000	0	-0.49	1	1
NICD/RBPSUH	0.009	0.13	-10000	0	-0.48	31	31
WIF1	-0.12	0.17	0.17	7	-0.31	220	227
NOTCH1	-0.009	0.13	-10000	0	-0.51	31	31
PSENEN	0.027	0.003	-10000	0	-10000	0	0
KREMEN2	0.023	0.062	0.17	21	-0.31	13	34
DKK1	-0.029	0.13	0.17	12	-0.31	87	99
beta catenin/beta TrCP1	0.037	0.058	0.26	5	-0.24	2	7
APH1B	0.027	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.006	-10000	0	-10000	0	0
AXIN1	0.002	0.069	0.25	2	-0.31	5	7
CtBP/CBP/TCF1/TLE1/AES	0.018	0.024	-10000	0	-0.17	1	1
PSEN1	0.027	0.004	-10000	0	-10000	0	0
FOS	-0.026	0.12	0.17	4	-0.31	78	82
JUN	0.024	0.031	0.17	1	-0.31	4	5
MAP3K7	0.022	0.01	-10000	0	-10000	0	0
CTNNB1	0.027	0.059	0.25	6	-0.25	2	8
MAPK3	0.026	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.035	0.067	0.24	2	-0.19	32	34
HNF1A	0.04	0.046	0.17	51	-10000	0	51
CTBP1	0.026	0.004	-10000	0	-10000	0	0
MYC	0.025	0.021	-10000	0	-10000	0	0
NKD1	0.005	0.083	0.17	6	-0.31	31	37
FZD1	0.024	0.017	-10000	0	-0.31	1	1
NOTCH1 precursor/Deltex homolog 1	0.012	0.13	-10000	0	-0.49	30	30
apoptosis	-0.026	0.1	-10000	0	-0.24	76	76
Delta 1/NOTCHprecursor	0.008	0.13	-10000	0	-0.49	31	31
DLL1	0.022	0.04	-10000	0	-0.31	7	7
PPARD	0.025	0.052	-10000	0	-0.76	2	2
Gamma Secretase	0.073	0.025	-10000	0	-10000	0	0
APC	-0.018	0.11	0.24	2	-0.36	30	32
DVL1	-0.001	0.032	-10000	0	-0.23	5	5
CSNK2A1	0.027	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.007	0.096	-10000	0	-0.18	91	91
LRP6	0.024	0.009	-10000	0	-10000	0	0
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
NLK	0.009	0.004	-10000	0	-10000	0	0
CCND1	0.027	0.014	-10000	0	-10000	0	0
WNT1	0.029	0.023	0.17	12	-10000	0	12
Axin1/APC/beta catenin	0.018	0.09	0.32	9	-0.37	7	16
DKK2	0.016	0.072	0.17	12	-0.31	21	33
NOTCH1 precursor/DVL1	-0.005	0.12	-10000	0	-0.47	26	26
GSK3B	0.025	0.007	-10000	0	-10000	0	0
FRAT1	0.025	0.007	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.014	0.14	-10000	0	-0.5	30	30
PPP2R5D	0.022	0.052	0.2	9	-0.37	3	12
MAPK1	0.027	0.004	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.034	0.11	-10000	0	-0.16	199	199
RBPJ	0.026	0.005	-10000	0	-10000	0	0
CREBBP	0.028	0.006	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	0.001	0.077	0.15	1	-0.33	22	23
PDGF/PDGFRA/CRKL	0.018	0.057	-10000	0	-0.22	21	21
positive regulation of JUN kinase activity	0.05	0.047	-10000	0	-0.17	17	17
CRKL	0.026	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.024	0.11	0.14	15	-0.23	105	120
AP1	-0.13	0.28	-10000	0	-0.74	80	80
mol:IP3	-0.029	0.052	-10000	0	-0.25	21	21
PLCG1	-0.029	0.052	-10000	0	-0.25	21	21
PDGF/PDGFRA/alphaV Integrin	0.018	0.057	-10000	0	-0.22	22	22
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.029	0.052	-10000	0	-0.25	21	21
CAV3	-0.031	0.13	0.17	17	-0.31	90	107
CAV1	-0.013	0.1	-10000	0	-0.31	55	55
SHC/Grb2/SOS1	0.051	0.048	-10000	0	-0.17	17	17
PDGF/PDGFRA/Shf	0.019	0.058	0.14	1	-0.23	20	21
FOS	-0.13	0.27	0.3	1	-0.73	80	81
JUN	-0.031	0.03	-10000	0	-0.28	3	3
oligodendrocyte development	0.018	0.057	-10000	0	-0.22	22	22
GRB2	0.026	0.005	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:DAG	-0.029	0.052	-10000	0	-0.25	21	21
PDGF/PDGFRA	0.001	0.077	0.15	1	-0.33	22	23
actin cytoskeleton reorganization	0.018	0.058	-10000	0	-0.23	20	20
SRF	-0.005	0.017	-10000	0	-10000	0	0
SHC1	0.026	0.006	-10000	0	-10000	0	0
PI3K	0.033	0.057	-10000	0	-0.21	22	22
PDGF/PDGFRA/Crk/C3G	0.037	0.048	-10000	0	-0.18	19	19
JAK1	-0.023	0.043	-10000	0	-0.22	20	20
ELK1/SRF	-0.026	0.048	0.15	11	-0.21	20	31
SHB	0.024	0.026	-10000	0	-0.31	3	3
SHF	0.026	0.017	0.17	1	-0.31	1	2
CSNK2A1	0.032	0.018	-10000	0	-10000	0	0
GO:0007205	-0.026	0.059	-10000	0	-0.28	21	21
SOS1	0.026	0.005	-10000	0	-10000	0	0
Ras protein signal transduction	0.05	0.047	-10000	0	-0.17	17	17
PDGF/PDGFRA/SHB	0.018	0.058	-10000	0	-0.23	20	20
PDGF/PDGFRA/Caveolin-1	-0.007	0.1	-10000	0	-0.27	57	57
ITGAV	0.026	0.005	-10000	0	-10000	0	0
ELK1	-0.032	0.06	0.22	1	-0.27	21	22
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
PDGF/PDGFRA/Crk	0.017	0.057	-10000	0	-0.22	22	22
JAK-STAT cascade	-0.023	0.043	-10000	0	-0.22	20	20
cell proliferation	0.019	0.058	0.14	1	-0.23	20	21

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.009	-10000	0	-10000	0	0
AES	0.024	0.008	-10000	0	-10000	0	0
FBXW11	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.032	0.02	-10000	0	-0.21	1	1
SMAD4	0.025	0.008	-10000	0	-10000	0	0
DKK2	0.016	0.072	0.17	12	-0.31	21	33
TLE1	0.024	0.007	-10000	0	-10000	0	0
MACF1	0.028	0.002	-10000	0	-10000	0	0
CTNNB1	0.071	0.099	0.3	37	-0.42	1	38
WIF1	-0.12	0.17	0.17	7	-0.31	220	227
beta catenin/RanBP3	0.029	0.068	0.44	5	-0.34	1	6
KREMEN2	0.023	0.062	0.17	21	-0.31	13	34
DKK1	-0.029	0.13	0.17	12	-0.31	87	99
beta catenin/beta TrCP1	0.075	0.091	0.3	26	-0.38	1	27
FZD1	0.024	0.017	-10000	0	-0.31	1	1
AXIN2	-0.005	0.15	0.5	9	-1.3	5	14
AXIN1	0.027	0.006	-10000	0	-10000	0	0
RAN	0.026	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.028	0.083	-10000	0	-0.52	8	8
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.042	0.11	0.28	13	-0.4	12	25
Axin1/APC/GSK3	0.042	0.056	0.24	11	-0.43	1	12
Axin1/APC/GSK3/beta catenin/Macf1	0.038	0.091	0.32	17	-0.36	6	23
HNF1A	0.039	0.046	0.17	51	-10000	0	51
CTBP1	0.024	0.007	-10000	0	-10000	0	0
MYC	0.12	0.22	0.54	101	-10000	0	101
RANBP3	0.026	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.035	0.067	0.24	2	-0.18	32	34
NKD1	0.005	0.083	0.17	6	-0.31	31	37
TCF4	0.02	0.028	-10000	0	-0.31	3	3
TCF3	0.024	0.008	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.056	0.035	-10000	0	-0.16	1	1
Ran/GTP	0.019	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.004	0.068	0.39	3	-0.34	3	6
LEF1	0.026	0.048	0.17	21	-0.31	6	27
DVL1	0.034	0.035	0.18	1	-10000	0	1
CSNK2A1	0.027	0.004	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.059	0.086	0.29	11	-0.35	4	15
DKK1/LRP6/Kremen 2	0.008	0.096	0.15	1	-0.18	91	92
LRP6	0.025	0.009	-10000	0	-10000	0	0
CSNK1A1	0.025	0.009	-10000	0	-10000	0	0
NLK	0.027	0.006	-10000	0	-10000	0	0
CCND1	0.024	0.12	0.53	21	-10000	0	21
WNT1	0.029	0.024	0.18	12	-10000	0	12
GSK3A	0.027	0.006	-10000	0	-10000	0	0
GSK3B	0.026	0.007	-10000	0	-10000	0	0
FRAT1	0.025	0.007	-10000	0	-10000	0	0
PPP2R5D	0.042	0.063	0.23	27	-0.34	3	30
APC	0.009	0.077	0.21	51	-10000	0	51
WNT1/LRP6/FZD1	0.059	0.078	0.17	152	-10000	0	152
CREBBP	0.024	0.007	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.01	0.008	0.058	2	-10000	0	2
RAS family/GTP	0.001	0.092	-10000	0	-0.23	20	20
NFATC4	-0.035	0.063	0.28	6	-0.24	4	10
ERBB2IP	0.025	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.026	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.014	0.069	0.16	1	-0.19	51	52
JUN	-0.009	0.071	0.23	7	-0.3	1	8
HRAS	0.028	0.017	0.17	6	-10000	0	6
DOCK7	-0.04	0.058	0.29	1	-0.2	16	17
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.01	0.067	-10000	0	-0.17	51	51
AKT1	-0.005	0.007	-10000	0	-10000	0	0
BAD	-0.01	0.005	-10000	0	-10000	0	0
MAPK10	-0.017	0.061	0.19	20	-0.18	3	23
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.013	0.074	0.17	1	-0.2	51	52
RAF1	-0.014	0.092	0.3	9	-0.24	21	30
ErbB2/ErbB3/neuregulin 2	-0.028	0.092	-10000	0	-0.18	129	129
STAT3	-0.01	0.19	-10000	0	-0.9	22	22
cell migration	-0.005	0.088	0.26	31	-0.18	4	35
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.034	0.18	0.4	5	-0.5	28	33
FOS	-0.053	0.19	0.32	8	-0.45	85	93
NRAS	0.026	0.016	-10000	0	-0.31	1	1
mol:Ca2+	-0.014	0.069	0.16	1	-0.19	51	52
MAPK3	-0.017	0.14	0.37	7	-0.45	13	20
MAPK1	-0.021	0.15	0.36	8	-0.46	18	26
JAK2	-0.039	0.058	0.29	1	-0.2	14	15
NF2	0.003	0.055	-10000	0	-0.69	3	3
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.011	0.066	-10000	0	-0.2	48	48
NRG1	-0.019	0.1	-10000	0	-0.31	56	56
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
MAPK8	-0.042	0.096	0.2	1	-0.24	57	58
MAPK9	-0.016	0.058	0.18	20	-0.16	1	21
ERBB2	-0.021	0.02	0.24	1	-0.23	2	3
ERBB3	0.025	0.016	-10000	0	-0.31	1	1
SHC1	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
apoptosis	0.01	0.01	-10000	0	-10000	0	0
STAT3 (dimer)	-0.01	0.19	-10000	0	-0.86	23	23
RNF41	-0.014	0.007	-10000	0	-10000	0	0
FRAP1	-0.005	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.037	0.04	-10000	0	-0.15	47	47
ErbB2/ErbB2/HSP90 (dimer)	-0.019	0.019	0.18	1	-0.19	2	3
CHRNA1	-0.008	0.12	0.34	8	-0.36	12	20
myelination	-0.017	0.099	0.32	24	-0.24	3	27
PPP3CB	-0.038	0.054	0.28	1	-0.19	15	16
KRAS	0.025	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.004	0.083	-10000	0	-0.19	46	46
NRG2	-0.08	0.16	-10000	0	-0.31	155	155
mol:GDP	-0.011	0.066	-10000	0	-0.2	48	48
SOS1	0.026	0.005	-10000	0	-10000	0	0
MAP2K2	-0.022	0.089	0.26	11	-0.26	21	32
SRC	0.026	0.006	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.04	0.057	0.29	1	-0.2	15	16
MAP2K1	-0.041	0.15	0.32	1	-0.49	18	19
heart morphogenesis	-0.014	0.069	0.16	1	-0.19	51	52
RAS family/GDP	0.006	0.092	-10000	0	-0.22	19	19
GRB2	0.026	0.005	-10000	0	-10000	0	0
PRKACA	0.007	0.058	-10000	0	-0.72	3	3
CHRNE	0.003	0.02	0.14	3	-0.15	1	4
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
activation of caspase activity	0.005	0.007	-10000	0	-10000	0	0
nervous system development	-0.014	0.069	0.16	1	-0.19	51	52
CDC42	0.027	0.003	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.026	0.005	-10000	0	-10000	0	0
VLDLR	0.026	0.016	-10000	0	-0.31	1	1
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
NUDC	0.027	0.002	-10000	0	-10000	0	0
RELN/LRP8	0.057	0.045	0.24	3	-0.17	4	7
CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
KATNA1	0.027	0.004	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.005	0.056	0.18	38	-0.17	3	41
IQGAP1/CaM	0.039	0.008	-10000	0	-10000	0	0
DAB1	-0.095	0.16	0.17	2	-0.31	178	180
IQGAP1	0.027	0.003	-10000	0	-10000	0	0
PLA2G7	0.061	0.065	0.17	119	-0.31	1	120
CALM1	0.026	0.005	-10000	0	-10000	0	0
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.04	0.015	0.14	6	-10000	0	6
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.026	0.006	-10000	0	-10000	0	0
CDK5R1	0.034	0.031	0.17	23	-10000	0	23
LIS1/Poliovirus Protein 3A	-0.009	0.003	-10000	0	-10000	0	0
CDK5R2	0.041	0.045	0.17	50	-10000	0	50
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.026	0.12	-10000	0	-0.19	161	161
YWHAE	0.025	0.007	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.031	0.077	0.27	34	-0.21	1	35
MAP1B	-0.009	0.054	-10000	0	-0.22	30	30
RAC1	0.01	0.005	-10000	0	-10000	0	0
p35/CDK5	-0.009	0.053	0.2	20	-10000	0	20
RELN	0.04	0.059	0.17	60	-0.31	4	64
PAFAH/LIS1	0.046	0.046	0.13	106	-0.18	1	107
LIS1/CLIP170	0.024	0.009	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.018	0.042	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.048	0.1	-10000	0	-0.28	28	28
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.012	0.078	0.25	40	-0.2	1	41
LIS1/IQGAP1	0.025	0.008	-10000	0	-10000	0	0
RHOA	0.011	0.004	-10000	0	-10000	0	0
PAFAH1B1	-0.011	0.004	-10000	0	-10000	0	0
PAFAH1B3	0.031	0.028	0.17	17	-10000	0	17
PAFAH1B2	0.016	0.056	-10000	0	-0.31	14	14
MAP1B/LIS1/Dynein heavy chain	0.006	0.048	-10000	0	-0.17	2	2
NDEL1/Katanin 60/Dynein heavy chain	0.034	0.074	0.31	17	-10000	0	17
LRP8	0.028	0.018	0.17	7	-10000	0	7
NDEL1/Katanin 60	0.027	0.078	0.26	35	-0.21	1	36
P39/CDK5	0	0.069	0.23	24	-0.18	1	25
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.025	0.009	-10000	0	-10000	0	0
CDK5	-0.015	0.036	0.17	14	-10000	0	14
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.021	0.008	-10000	0	-10000	0	0
CSNK2A1	0.027	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.016	0.11	-10000	0	-0.16	157	157
RELN/VLDLR	0.07	0.051	0.25	3	-0.16	5	8
CDC42	0.011	0.004	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.017	0.039	0.16	4	-0.2	11	15
EPHB2	0.025	0.032	0.17	3	-0.31	4	7
Syndecan-2/TACI	0.029	0.051	0.16	42	-0.17	7	49
LAMA1	0.02	0.07	0.17	22	-0.31	17	39
Syndecan-2/alpha2 ITGB1	0.017	0.074	-10000	0	-0.18	49	49
HRAS	0.028	0.017	0.17	6	-10000	0	6
Syndecan-2/CASK	0.004	0.016	-10000	0	-0.17	4	4
ITGA5	0.018	0.054	0.17	1	-0.31	13	14
BAX	-0.008	0.025	-10000	0	-10000	0	0
EPB41	0.027	0.002	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.018	0.019	-10000	0	-0.15	4	4
LAMA3	0	0.09	0.17	1	-0.31	38	39
EZR	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.003	0.092	-10000	0	-0.31	41	41
Syndecan-2/MMP2	0.017	0.03	0.13	1	-0.19	8	9
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.013	0.073	-10000	0	-0.21	45	45
dendrite morphogenesis	0.02	0.027	0.13	3	-0.2	5	8
Syndecan-2/GM-CSF	0.018	0.027	0.17	6	-0.18	4	10
determination of left/right symmetry	0.006	0.019	-10000	0	-0.2	4	4
Syndecan-2/PKC delta	0.02	0.021	-10000	0	-0.17	4	4
GNB2L1	0.028	0.014	0.17	4	-10000	0	4
MAPK3	0.027	0.074	0.19	84	-0.16	4	88
MAPK1	0.03	0.077	0.19	91	-0.16	4	95
Syndecan-2/RACK1	0.032	0.029	0.22	2	-0.15	4	6
NF1	0.027	0.003	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.006	0.019	-10000	0	-0.2	4	4
ITGA2	-0.007	0.098	-10000	0	-0.31	47	47
MAPK8	-0.001	0.029	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.027	0.071	0.25	5	-0.17	35	40
Syndecan-2/Kininogen	0.032	0.054	0.16	58	-0.18	4	62
ITGB1	0.026	0.004	-10000	0	-10000	0	0
SRC	0.026	0.083	0.19	95	-0.14	4	99
Syndecan-2/CASK/Protein 4.1	0.018	0.019	-10000	0	-0.16	4	4
extracellular matrix organization	0.019	0.025	-10000	0	-0.21	4	4
actin cytoskeleton reorganization	0.017	0.038	0.16	4	-0.2	11	15
Syndecan-2/Caveolin-2/Ras	0.02	0.055	-10000	0	-0.18	28	28
Syndecan-2/Laminin alpha3	0.008	0.05	0.13	1	-0.18	31	32
Syndecan-2/RasGAP	0.04	0.033	0.23	2	-0.14	4	6
alpha5/beta1 Integrin	0.032	0.042	0.14	1	-0.21	13	14
PRKCD	0.026	0.005	-10000	0	-10000	0	0
Syndecan-2 dimer	0.02	0.027	0.13	3	-0.2	5	8
GO:0007205	0.002	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.024	0.027	0.18	4	-0.14	3	7
RHOA	0.026	0.005	-10000	0	-10000	0	0
SDCBP	0.022	0.01	-10000	0	-10000	0	0
TNFRSF13B	0.034	0.055	0.17	42	-0.31	5	47
RASA1	0.025	0.016	-10000	0	-0.31	1	1
alpha2/beta1 Integrin	0.013	0.073	-10000	0	-0.21	45	45
Syndecan-2/Synbindin	0.019	0.021	-10000	0	-0.17	4	4
TGFB1	0.026	0.016	-10000	0	-0.31	1	1
CASP3	0.04	0.071	0.19	87	-0.16	4	91
FN1	0.02	0.052	0.17	4	-0.31	11	15
Syndecan-2/IL8	0.018	0.057	0.16	24	-0.18	25	49
SDC2	0.006	0.02	-10000	0	-0.2	4	4
KNG1	0.037	0.05	0.17	58	-10000	0	58
Syndecan-2/Neurofibromin	0.02	0.021	-10000	0	-0.17	4	4
TRAPPC4	0.026	0.006	-10000	0	-10000	0	0
CSF2	0.022	0.018	0.17	6	-10000	0	6
Syndecan-2/TGFB1	0.019	0.025	-10000	0	-0.21	4	4
Syndecan-2/Syntenin/PI-4-5-P2	0.018	0.019	-10000	0	-0.16	4	4
Syndecan-2/Ezrin	0.031	0.025	-10000	0	-0.16	4	4
PRKACA	0.044	0.074	0.19	99	-0.16	4	103
angiogenesis	0.017	0.057	0.16	24	-0.18	25	49
MMP2	0.018	0.048	0.17	1	-0.31	10	11
IL8	0.01	0.094	0.17	24	-0.31	35	59
calcineurin-NFAT signaling pathway	0.029	0.051	0.16	42	-0.17	7	49

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.026	0.004	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.066	0.056	0.18	1	-0.18	2	3
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.005	0.031	-10000	0	-0.32	4	4
AURKB	0.067	0.069	0.17	145	-10000	0	145
AURKC	0.026	0.024	0.17	3	-0.31	2	5

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.002	0.049	0.2	26	-0.18	3	29
RFC1	-0.004	0.033	0.16	14	-0.18	3	17
PRKDC	0.016	0.069	0.2	57	-0.18	2	59
RIPK1	0.028	0.007	-10000	0	-10000	0	0
CASP7	-0.014	0.097	-10000	0	-0.55	13	13
FASLG/FAS/FADD/FAF1	-0.01	0.06	0.16	1	-0.22	22	23
MAP2K4	-0.062	0.16	0.25	3	-0.32	102	105
mol:ceramide	-0.023	0.099	0.22	1	-0.27	33	34
GSN	0	0.044	0.19	22	-0.18	3	25
FASLG/FAS/FADD/FAF1/Caspase 8	-0.017	0.076	0.2	1	-0.28	17	18
FAS	0.01	0.042	-10000	0	-0.31	6	6
BID	-0.024	0.013	-10000	0	-10000	0	0
MAP3K1	-0.021	0.098	0.26	5	-0.33	13	18
MAP3K7	0.017	0.017	-10000	0	-10000	0	0
RB1	-0.004	0.025	0.15	10	-0.16	1	11
CFLAR	0.029	0.005	-10000	0	-10000	0	0
HGF/MET	0.023	0.087	-10000	0	-0.22	47	47
ARHGDIB	-0.002	0.038	0.18	17	-0.18	3	20
FADD	0.015	0.023	-10000	0	-10000	0	0
actin filament polymerization	0	0.045	0.18	4	-0.19	22	26
NFKB1	-0.02	0.1	-10000	0	-0.53	5	5
MAPK8	-0.098	0.21	0.36	3	-0.47	107	110
DFFA	-0.005	0.031	0.16	13	-0.18	3	16
DNA fragmentation during apoptosis	-0.004	0.037	0.17	16	-0.18	5	21
FAS/FADD/MET	0.014	0.07	-10000	0	-0.19	39	39
CFLAR/RIP1	0.042	0.011	-10000	0	-10000	0	0
FAIM3	0.03	0.023	0.18	11	-10000	0	11
FAF1	0.015	0.026	-10000	0	-10000	0	0
PARP1	-0.005	0.028	0.15	11	-0.18	3	14
DFFB	-0.003	0.035	0.17	16	-0.18	3	19
CHUK	-0.021	0.091	-10000	0	-0.5	5	5
FASLG	0.012	0.064	0.18	13	-0.32	12	25
FAS/FADD	0.018	0.041	-10000	0	-0.23	6	6
HGF	0.011	0.075	0.17	9	-0.31	24	33
LMNA	-0.006	0.032	0.15	15	-0.16	3	18
CASP6	-0.005	0.028	0.15	12	-0.18	2	14
CASP10	0.011	0.046	0.17	1	-0.31	7	8
CASP3	0	0.031	0.19	12	-10000	0	12
PTPN13	0.025	0.022	-10000	0	-0.31	2	2
CASP8	-0.025	0.016	-10000	0	-0.13	1	1
IL6	-0.22	0.48	-10000	0	-1.1	106	106
MET	-0.004	0.093	-10000	0	-0.31	42	42
ICAD/CAD	-0.005	0.034	0.16	16	-0.18	1	17
FASLG/FAS/FADD/FAF1/Caspase 10	-0.023	0.099	0.22	1	-0.27	32	33
activation of caspase activity by cytochrome c	-0.024	0.013	-10000	0	-10000	0	0
PAK2	0.001	0.046	0.19	26	-0.19	2	28
BCL2	0.016	0.052	-10000	0	-0.31	12	12

×

BARD1 signaling events

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
BARD1/CSTF1	0.012	0.077	-10000	0	-0.21	51	51
ATM	0.025	0.016	-10000	0	-0.31	1	1
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
PRKDC	0.023	0.012	0.17	1	-10000	0	1
ATR	0.025	0.007	-10000	0	-10000	0	0
UBE2L3	0.026	0.005	-10000	0	-10000	0	0
FANCD2	0.017	0.011	0.2	1	-10000	0	1
protein ubiquitination	0.04	0.071	-10000	0	-0.16	49	49
XRCC5	0.027	0.004	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
M/R/N Complex	0.041	0.024	-10000	0	-10000	0	0
MRE11A	0.026	0.006	-10000	0	-10000	0	0
DNA-PK	0.045	0.023	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.011	0.05	-10000	0	-0.3	1	1
FANCF	0.027	0.004	-10000	0	-10000	0	0
BRCA1	0.026	0.009	0.17	1	-10000	0	1
CCNE1	0.028	0.015	0.17	5	-10000	0	5
CDK2/Cyclin E1	0.04	0.013	0.14	5	-10000	0	5
FANCG	0.026	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.012	0.077	0.14	1	-0.21	51	52
FANCE	0.027	0.004	-10000	0	-10000	0	0
FANCC	0.026	0.006	-10000	0	-10000	0	0
NBN	0.021	0.011	-10000	0	-10000	0	0
FANCA	0.03	0.042	0.17	28	-0.31	2	30
DNA repair	-0.01	0.067	0.62	1	-0.25	1	2
BRCA1/BARD1/ubiquitin	0.012	0.077	0.14	1	-0.21	51	52
BARD1/DNA-PK	0.033	0.072	-10000	0	-0.16	50	50
FANCL	0.026	0.004	-10000	0	-10000	0	0
mRNA polyadenylation	-0.012	0.077	0.21	51	-10000	0	51
BRCA1/BARD1/CTIP/M/R/N Complex	0.005	0.066	-10000	0	-0.18	47	47
BRCA1/BACH1/BARD1/TopBP1	0.025	0.071	-10000	0	-0.18	49	49
BRCA1/BARD1/P53	0.031	0.071	-10000	0	-0.16	49	49
BARD1/CSTF1/BRCA1	0.027	0.071	-10000	0	-0.18	49	49
BRCA1/BACH1	0.026	0.009	0.17	1	-10000	0	1
BARD1	-0.009	0.1	-10000	0	-0.31	53	53
PCNA	0.026	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.027	0.072	-10000	0	-0.18	51	51
BRCA1/BARD1/UbcH7	0.027	0.072	-10000	0	-0.18	51	51
BRCA1/BARD1/RAD51/PCNA	0.045	0.078	0.26	2	-0.17	49	51
BARD1/DNA-PK/P53	0.036	0.073	-10000	0	-0.15	50	50
BRCA1/BARD1/Ubiquitin	0.012	0.077	0.14	1	-0.21	51	52
BRCA1/BARD1/CTIP	0.016	0.064	-10000	0	-0.17	50	50
FA complex	0.023	0.035	0.19	3	-10000	0	3
BARD1/EWS	0.012	0.078	-10000	0	-0.21	53	53
RBBP8	-0.011	0.01	-10000	0	-0.21	1	1
TP53	0.023	0.01	-10000	0	-10000	0	0
TOPBP1	0.025	0.007	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.03	0.069	0.16	49	-10000	0	49
BRCA1/BARD1	0.045	0.074	-10000	0	-0.16	49	49
CSTF1	0.026	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.005	0.071	-10000	0	-0.21	53	53
CDK2	0.026	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.037	0.039	0.17	37	-10000	0	37
RAD50	0.026	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.012	0.077	0.14	1	-0.21	51	52
EWSR1	0.026	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.027	0.01	0.17	2	-10000	0	2
Jak2/Leptin Receptor	0.023	0.11	0.28	5	-0.37	16	21
PTP1B/AKT1	0.011	0.073	0.25	5	-0.21	11	16
FYN	0.022	0.018	-10000	0	-0.31	1	1
p210 bcr-abl/PTP1B	0.002	0.074	0.24	6	-0.22	12	18
EGFR	-0.004	0.092	-10000	0	-0.32	39	39
EGF/EGFR	0.003	0.099	0.19	1	-0.25	37	38
CSF1	0.019	0.05	-10000	0	-0.31	11	11
AKT1	0.027	0.005	-10000	0	-10000	0	0
INSR	0.027	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.007	0.095	0.27	3	-0.25	37	40
Insulin Receptor/Insulin	0.026	0.072	0.21	1	-0.22	4	5
HCK	0.024	0.031	0.17	1	-0.31	4	5
CRK	0.025	0.007	-10000	0	-10000	0	0
TYK2	-0.001	0.073	0.3	5	-0.25	6	11
EGF	0.02	0.087	0.18	40	-0.31	23	63
YES1	0.025	0.007	-10000	0	-10000	0	0
CAV1	-0.007	0.11	0.26	15	-0.29	31	46
TXN	0.026	0.01	0.17	1	-10000	0	1
PTP1B/IRS1/GRB2	0.014	0.085	0.24	1	-0.27	13	14
cell migration	-0.002	0.074	0.22	12	-0.24	6	18
STAT3	0.026	0.005	-10000	0	-10000	0	0
PRLR	0.019	0.077	0.18	22	-0.31	22	44
ITGA2B	0.02	0.048	0.17	5	-0.31	9	14
CSF1R	0.025	0.023	0.17	1	-0.31	2	3
Prolactin Receptor/Prolactin	0.031	0.059	-10000	0	-0.22	20	20
FGR	0.026	0.022	0.17	1	-0.31	2	3
PTP1B/p130 Cas	0.01	0.067	0.24	3	-0.22	9	12
Crk/p130 Cas	0.017	0.073	0.27	2	-0.22	7	9
DOK1	0.008	0.074	0.25	12	-0.23	5	17
JAK2	0.012	0.097	0.26	4	-0.36	15	19
Jak2/Leptin Receptor/Leptin	-0.008	0.11	-10000	0	-0.3	27	27
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
PTPN1	0.002	0.074	0.24	6	-0.23	12	18
LYN	0.023	0.01	-10000	0	-10000	0	0
CDH2	-0.047	0.14	0.17	9	-0.31	110	119
SRC	0.016	0.073	-10000	0	-0.37	13	13
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
CAT1/PTP1B	-0.003	0.11	0.3	17	-0.28	25	42
CAPN1	0.026	0.006	-10000	0	-10000	0	0
CSK	0.027	0.003	-10000	0	-10000	0	0
PI3K	0.029	0.076	-10000	0	-0.29	5	5
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.01	0.11	-10000	0	-0.28	46	46
negative regulation of transcription	0.013	0.097	0.26	4	-0.36	15	19
FCGR2A	0.025	0.024	0.17	2	-0.31	2	4
FER	0.017	0.053	-10000	0	-0.31	12	12
alphaIIb/beta3 Integrin	-0.014	0.1	0.14	2	-0.21	101	103
BLK	0	0.1	0.17	32	-0.31	43	75
Insulin Receptor/Insulin/Shc	0.048	0.022	-10000	0	-0.092	1	1
RHOA	0.027	0.006	-10000	0	-10000	0	0
LEPR	0.012	0.07	-10000	0	-0.3	23	23
BCAR1	0.022	0.011	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.026	0.005	-10000	0	-10000	0	0
mol:NADPH	0.001	0.004	-10000	0	-10000	0	0
TRPV6	-0.03	0.13	0.24	9	-0.31	48	57
PRL	0.006	0.026	0.17	4	-10000	0	4
SOCS3	-0.14	0.4	-10000	0	-1.1	69	69
SPRY2	0.021	0.031	-10000	0	-0.31	4	4
Insulin Receptor/Insulin/IRS1	0.043	0.044	-10000	0	-0.18	15	15
CSF1/CSF1R	0.016	0.088	0.27	2	-0.28	15	17
Ras protein signal transduction	0.004	0.084	0.48	13	-10000	0	13
IRS1	0.017	0.058	-10000	0	-0.31	15	15
INS	0.015	0.03	0.18	12	-10000	0	12
LEP	0.017	0.028	0.17	10	-10000	0	10
STAT5B	0.009	0.079	0.24	8	-0.26	10	18
STAT5A	0.009	0.079	0.24	8	-0.27	9	17
GRB2	0.026	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.076	0.25	4	-0.22	11	15
CSN2	0	0.051	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
LAT	0.012	0.092	-10000	0	-0.39	20	20
YBX1	0.033	0.005	-10000	0	-10000	0	0
LCK	0.03	0.02	0.17	9	-10000	0	9
SHC1	0.026	0.006	-10000	0	-10000	0	0
NOX4	0.096	0.076	0.18	230	-10000	0	230

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.028	0.13	0.28	12	-0.36	34	46
IKBKB	-0.008	0.11	0.3	14	-0.26	41	55
AKT1	0.02	0.1	0.28	39	-0.19	12	51
IKBKG	0.028	0.074	0.28	14	-0.24	6	20
CALM1	0.01	0.084	0.28	8	-0.32	10	18
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
MAP3K1	-0.055	0.18	0.33	8	-0.47	52	60
MAP3K7	0.022	0.01	-10000	0	-10000	0	0
mol:Ca2+	0.01	0.082	0.25	7	-0.34	10	17
DOK1	0.026	0.016	-10000	0	-0.31	1	1
AP-1	-0.01	0.082	0.27	10	-0.23	22	32
LYN	0.023	0.01	-10000	0	-10000	0	0
BLNK	0.024	0.017	-10000	0	-0.31	1	1
SHC1	0.026	0.006	-10000	0	-10000	0	0
BCR complex	0.039	0.08	0.18	53	-0.23	26	79
CD22	-0.015	0.1	0.18	1	-0.33	32	33
CAMK2G	0.008	0.078	0.28	7	-0.33	7	14
CSNK2A1	0.027	0.004	-10000	0	-10000	0	0
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
SHC/GRB2/SOS1	0.021	0.046	-10000	0	-0.17	18	18
GO:0007205	0.011	0.085	0.27	5	-0.34	11	16
SYK	0.023	0.035	0.17	1	-0.31	5	6
ELK1	0.008	0.085	0.26	6	-0.32	12	18
NFATC1	0	0.1	0.29	15	-0.31	18	33
B-cell antigen/BCR complex	0.039	0.08	0.18	53	-0.23	26	79
PAG1/CSK	0.032	0.017	-10000	0	-10000	0	0
NFKBIB	0.015	0.046	0.15	14	-0.12	7	21
HRAS	0.019	0.078	0.27	13	-0.27	5	18
NFKBIA	0.016	0.045	0.15	14	-0.12	7	21
NF-kappa-B/RelA/I kappa B beta	0.019	0.04	0.15	16	-10000	0	16
RasGAP/Csk	0.064	0.085	0.27	19	-0.18	33	52
mol:GDP	0.013	0.086	0.26	6	-0.31	13	19
PTEN	0.021	0.011	-10000	0	-10000	0	0
CD79B	0.024	0.057	0.17	16	-0.31	11	27
NF-kappa-B/RelA/I kappa B alpha	0.02	0.04	0.14	17	-10000	0	17
GRB2	0.026	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.022	0.14	0.35	8	-0.43	24	32
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:IP3	0.011	0.079	0.24	9	-0.35	10	19
CSK	0.027	0.003	-10000	0	-10000	0	0
FOS	-0.012	0.094	0.3	5	-0.34	13	18
CHUK	0.014	0.1	0.28	14	-0.28	29	43
IBTK	0.023	0.01	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.025	0.077	0.25	7	-0.32	5	12
PTPN6	-0.021	0.095	-10000	0	-0.41	20	20
RELA	0.026	0.006	-10000	0	-10000	0	0
BCL2A1	0.015	0.03	0.12	10	-10000	0	10
VAV2	-0.019	0.1	0.33	1	-0.45	16	17
ubiquitin-dependent protein catabolic process	0.017	0.045	0.15	14	-0.12	7	21
BTK	0.024	0.097	-10000	0	-0.92	4	4
CD19	-0.025	0.1	0.19	2	-0.35	29	31
MAP4K1	0.031	0.048	0.17	26	-0.31	5	31
CD72	0.03	0.04	0.17	20	-0.31	3	23
PAG1	0.021	0.011	-10000	0	-10000	0	0
MAPK14	-0.046	0.16	0.32	10	-0.4	51	61
SH3BP5	0.026	0.005	-10000	0	-10000	0	0
PIK3AP1	0.009	0.082	0.3	3	-0.37	11	14
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.014	0.096	0.29	1	-0.43	13	14
RAF1	0.019	0.079	0.28	15	-0.28	4	19
RasGAP/p62DOK/SHIP	0.053	0.098	0.24	19	-0.2	46	65
CD79A	0.029	0.083	0.17	53	-0.31	20	73
re-entry into mitotic cell cycle	-0.01	0.081	0.27	10	-0.23	20	30
RASA1	0.025	0.016	-10000	0	-0.31	1	1
MAPK3	0.017	0.08	0.28	19	-0.25	3	22
MAPK1	0.014	0.076	0.29	15	-0.25	3	18
CD72/SHP1	0	0.11	0.24	5	-0.39	21	26
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.048	0.16	0.33	10	-0.4	54	64
actin cytoskeleton organization	-0.01	0.098	0.3	7	-0.37	16	23
NF-kappa-B/RelA	0.041	0.077	0.28	13	-10000	0	13
Calcineurin	0.023	0.07	0.25	4	-0.32	5	9
PI3K	-0.017	0.086	-10000	0	-0.31	23	23
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.007	0.081	0.22	1	-0.38	14	15
SOS1	0.026	0.005	-10000	0	-10000	0	0
Bam32/HPK1	-0.081	0.3	-10000	0	-0.74	77	77
DAPP1	-0.11	0.32	-10000	0	-0.83	77	77
cytokine secretion	0.001	0.097	0.28	15	-0.29	18	33
mol:DAG	0.011	0.079	0.24	9	-0.35	10	19
PLCG2	0.021	0.026	0.17	2	-0.31	2	4
MAP2K1	0.016	0.076	0.27	15	-0.28	3	18
B-cell antigen/BCR complex/FcgammaRIIB	0.048	0.086	0.26	20	-0.2	32	52
mol:PI-3-4-5-P3	-0.024	0.061	0.18	6	-0.23	17	23
ETS1	0.01	0.082	0.28	14	-0.33	5	19
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.059	0.073	0.26	13	-0.18	20	33
B-cell antigen/BCR complex/LYN	0.001	0.098	0.23	1	-0.33	27	28
MALT1	0.023	0.019	0.17	1	-0.31	1	2
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	-0.015	0.097	0.28	3	-0.39	16	19
B-cell antigen/BCR complex/LYN/SYK	0.023	0.11	0.28	1	-0.35	21	22
CARD11	0.021	0.098	0.28	27	-0.33	8	35
FCGR2B	0.023	0.051	0.17	12	-0.31	9	21
PPP3CA	0.027	0.012	0.17	3	-10000	0	3
BCL10	0.026	0.005	-10000	0	-10000	0	0
IKK complex	0.012	0.056	0.19	28	-0.11	6	34
PTPRC	0.016	0.066	0.17	7	-0.31	18	25
PDPK1	-0.013	0.061	0.22	14	-0.18	13	27
PPP3CB	0.026	0.005	-10000	0	-10000	0	0
PPP3CC	0.019	0.013	-10000	0	-10000	0	0
POU2F2	0.014	0.03	0.12	7	-0.099	1	8

×

Visual signal transduction: Rods

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
mol:K +	0.027	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.015	0.008	0.12	2	-10000	0	2
Metarhodopsin II/Arrestin	0.026	0.012	0.13	3	-10000	0	3
PDE6G/GNAT1/GTP	0.039	0.029	0.12	48	-10000	0	48
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.02	0.011	0.17	2	-10000	0	2
GRK1	0.02	0.015	0.17	4	-10000	0	4
CNG Channel	0.021	0.076	-10000	0	-0.17	57	57
mol:Na +	0.03	0.042	-10000	0	-0.16	7	7
mol:ADP	0.02	0.015	0.17	4	-10000	0	4
RGS9-1/Gbeta5/R9AP	0.005	0.095	-10000	0	-0.18	100	100
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.044	0.044	-10000	0	-0.16	7	7
CNGB1	0.024	0.022	0.17	9	-10000	0	9
RDH5	0.016	0.061	0.17	3	-0.31	16	19
SAG	0.02	0.008	0.17	1	-10000	0	1
mol:Ca2+	-0.021	0.069	0.36	10	-10000	0	10
Na + (4 Units)	0.019	0.042	-10000	0	-0.15	7	7
RGS9	-0.041	0.14	0.17	3	-0.31	100	103
GNB1/GNGT1	0.031	0.013	-10000	0	-10000	0	0
GNAT1/GDP	0.014	0.086	-10000	0	-0.16	97	97
GUCY2D	0.036	0.06	0.17	55	-0.31	5	60
GNGT1	0.017	0.012	0.17	2	-10000	0	2
GUCY2F	0.019	0.007	0.17	1	-10000	0	1
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.007	0.067	0.16	3	-0.17	58	61
mol:11-cis-retinal	0.016	0.061	0.17	3	-0.31	16	19
mol:cGMP	0.039	0.034	-10000	0	-0.16	6	6
GNB1	0.027	0.004	-10000	0	-10000	0	0
Rhodopsin	0.026	0.044	-10000	0	-0.22	14	14
SLC24A1	0.027	0.003	-10000	0	-10000	0	0
CNGA1	0.025	0.032	0.17	3	-0.31	4	7
Metarhodopsin II	0.024	0.014	0.12	6	-10000	0	6
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.058	0.05	0.24	4	-0.17	6	10
RGS9BP	0.026	0.022	0.17	1	-0.31	2	3
Metarhodopsin II/Transducin	0.009	0.006	-10000	0	-10000	0	0
GCAP Family/Ca ++	0.044	0.021	-10000	0	-0.16	1	1
PDE6A/B	0.002	0.096	-10000	0	-0.24	65	65
mol:Pi	0.005	0.095	-10000	0	-0.18	100	100
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.038	0.017	-10000	0	-10000	0	0
PDE6B	-0.01	0.1	0.17	1	-0.31	54	55
PDE6A	0.013	0.069	0.17	3	-0.31	21	24
PDE6G	0.041	0.044	0.17	48	-10000	0	48
RHO	0.02	0.012	0.17	2	-10000	0	2
PDE6	0.009	0.13	0.23	1	-0.2	126	127
GUCA1A	0.023	0.011	0.17	2	-10000	0	2
GC2/GCAP Family	0.055	0.023	-10000	0	-0.17	1	1
GUCA1C	0.018	0.008	0.17	1	-10000	0	1
GUCA1B	0.031	0.03	0.17	15	-0.31	1	16

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.028	0.016	-10000	0	-0.31	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.006	0.15	0.65	14	-0.7	1	15
IL27/IL27R/JAK1	0.046	0.19	0.39	8	-0.93	9	17
TBX21	0.022	0.16	0.37	16	-0.48	14	30
IL12B	0.034	0.036	0.18	30	-10000	0	30
IL12A	-0.003	0.03	0.25	1	-0.21	8	9
IL6ST	-0.029	0.13	0.19	1	-0.31	81	82
IL27RA/JAK1	0.009	0.15	0.45	1	-1.1	9	10
IL27	0.03	0.033	0.19	16	-10000	0	16
TYK2	0.029	0.011	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.016	0.11	0.46	1	-0.36	1	2
T-helper 2 cell differentiation	0.006	0.15	0.65	14	-0.7	1	15
T cell proliferation during immune response	0.006	0.15	0.65	14	-0.7	1	15
MAPKKK cascade	-0.006	0.15	0.7	1	-0.65	14	15
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT2	0.026	0.004	-10000	0	-10000	0	0
STAT1	0.032	0.02	0.17	9	-10000	0	9
IL12RB1	0.029	0.047	0.18	18	-0.31	6	24
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.02	0.17	0.41	17	-0.49	14	31
IL27/IL27R/JAK2/TYK2	-0.007	0.15	0.7	1	-0.66	14	15
positive regulation of T cell mediated cytotoxicity	-0.006	0.15	0.7	1	-0.65	14	15
STAT1 (dimer)	0.077	0.24	0.5	81	-0.62	14	95
JAK2	0.026	0.017	-10000	0	-0.31	1	1
JAK1	0.029	0.009	0.14	1	-10000	0	1
STAT2 (dimer)	-0.001	0.15	0.59	1	-0.62	14	15
T cell proliferation	-0.024	0.15	0.37	7	-0.48	25	32
IL12/IL12R/TYK2/JAK2	0.039	0.088	-10000	0	-0.63	2	2
IL17A	-0.016	0.11	0.47	1	-0.36	1	2
mast cell activation	0.006	0.15	0.65	14	-0.7	1	15
IFNG	0.007	0.029	0.14	3	-0.092	10	13
T cell differentiation	-0.001	0.005	0.012	8	-0.019	14	22
STAT3 (dimer)	-0.002	0.15	0.44	2	-0.62	14	16
STAT5A (dimer)	-0.002	0.15	0.44	2	-0.62	14	16
STAT4 (dimer)	0	0.15	0.44	2	-0.63	14	16
STAT4	0.028	0.039	0.17	13	-0.31	4	17
T cell activation	-0.005	0.013	0.12	5	-10000	0	5
IL27R/JAK2/TYK2	0.004	0.16	-10000	0	-0.9	10	10
GATA3	-0.35	0.54	0.65	3	-1.2	145	148
IL18	-0.01	0.032	-10000	0	-0.21	12	12
positive regulation of mast cell cytokine production	-0.002	0.14	0.44	2	-0.61	14	16
IL27/EBI3	0.045	0.039	0.17	5	-0.22	4	9
IL27RA	-0.011	0.16	-10000	0	-1.1	9	9
IL6	-0.021	0.14	0.18	25	-0.31	90	115
STAT5A	0.026	0.005	-10000	0	-10000	0	0
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.004	0.069	0.45	9	-10000	0	9
IL1B	-0.028	0.061	-10000	0	-0.21	49	49
EBI3	0.029	0.041	0.18	9	-0.31	5	14
TNF	-0.016	0.046	0.25	1	-0.21	24	25

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.027	0.01	0.17	2	-10000	0	2
mol:S1P	0.001	0.001	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.026	0.1	0.15	1	-0.25	74	75
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
S1P/S1P3/G12/G13	0.04	0.04	-10000	0	-0.16	14	14
AKT1	0.007	0.07	-10000	0	-0.46	6	6
AKT3	-0.016	0.12	-10000	0	-0.75	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.027	0.01	0.17	2	-10000	0	2
GNAI2	0.027	0.006	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.016	0.06	0.18	1	-0.31	16	17
S1PR2	0.027	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.021	0.12	-10000	0	-0.36	44	44
MAPK3	-0.027	0.12	-10000	0	-0.35	43	43
MAPK1	-0.024	0.11	-10000	0	-0.35	40	40
JAK2	-0.028	0.12	0.18	2	-0.36	48	50
CXCR4	-0.022	0.11	0.16	1	-0.36	39	40
FLT1	0.026	0.029	0.18	2	-0.31	3	5
RhoA/GDP	0.019	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
SRC	-0.025	0.11	-10000	0	-0.35	41	41
S1P/S1P3/Gi	-0.022	0.12	-10000	0	-0.36	44	44
RAC1	0.025	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.014	0.12	-10000	0	-0.33	46	46
VEGFA	0.012	0.077	0.18	5	-0.31	26	31
S1P/S1P2/Gi	-0.016	0.11	-10000	0	-0.26	69	69
VEGFR1 homodimer/VEGFA homodimer	0.029	0.062	0.16	6	-0.22	27	33
RHOA	0.026	0.005	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.001	0.074	-10000	0	-0.22	42	42
GNAQ	0.026	0.006	-10000	0	-10000	0	0
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
G12/G13	0.035	0.013	-10000	0	-10000	0	0
GNA14	0.025	0.016	-10000	0	-0.31	1	1
GNA15	0.012	0.068	-10000	0	-0.31	21	21
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
GNA11	0.016	0.058	-10000	0	-0.31	15	15
Rac1/GTP	-0.015	0.12	-10000	0	-0.34	41	41

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.026	0.004	-10000	0	-10000	0	0
ITGB7	0.015	0.064	0.17	3	-0.31	18	21
ITGA4	0.021	0.059	0.17	11	-0.31	13	24
alpha4/beta7 Integrin	0.026	0.067	0.18	10	-0.23	27	37
alpha4/beta1 Integrin	0.034	0.045	-10000	0	-0.21	13	13

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.019	0.004	-10000	0	-10000	0	0
PRKCZ	0.027	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.025	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.004	0.055	-10000	0	-0.21	15	15
IRAK/TOLLIP	0.028	0.008	-10000	0	-10000	0	0
IKBKB	0.021	0.011	-10000	0	-10000	0	0
IKBKG	0.027	0.002	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.012	0.1	0.14	3	-0.22	96	99
IL1A	0.022	0.029	0.17	3	-0.31	3	6
IL1B	-0.037	0.075	0.26	1	-0.24	52	53
IRAK/TRAF6/p62/Atypical PKCs	0.062	0.032	-10000	0	-10000	0	0
IL1R2	-0.036	0.13	-10000	0	-0.31	93	93
IL1R1	0.026	0.021	-10000	0	-0.31	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.047	-10000	0	-0.2	5	5
TOLLIP	0.027	0.004	-10000	0	-10000	0	0
TICAM2	0.02	0.04	-10000	0	-0.31	7	7
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.015	0.007	-10000	0	-10000	0	0
IKK complex/ELKS	0.003	0.085	0.26	3	-0.31	11	14
JUN	-0.008	0.054	0.18	27	-0.15	11	38
MAP3K7	0.022	0.01	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.033	0.083	-10000	0	-0.17	58	58
IL1 alpha/IL1R1/IL1RAP/MYD88	0.058	0.036	-10000	0	-0.19	6	6
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.067	0.039	-10000	0	-0.18	6	6
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.074	0.2	1	-0.18	56	57
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.001	0.055	0.19	29	-0.14	9	38
IRAK1	0.012	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.03	0.053	0.14	7	-0.21	21	28
IRAK4	0.027	0.004	-10000	0	-10000	0	0
PRKCI	0.025	0.01	0.17	1	-10000	0	1
TRAF6	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.031	0.034	-10000	0	-0.24	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.005	0.06	-10000	0	-0.22	15	15
CHUK	0.025	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.074	0.2	1	-0.18	56	57
IL1 beta/IL1R2	-0.031	0.11	-10000	0	-0.21	121	121
IRAK/TRAF6/TAK1/TAB1/TAB2	0.03	0.016	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.02	0.074	-10000	0	-0.17	48	48
IRAK3	0.012	0.066	-10000	0	-0.31	20	20
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.034	0.083	0.21	1	-0.17	60	61
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.021	0.028	-10000	0	-0.21	6	6
IL1 alpha/IL1R1/IL1RAP	0.046	0.034	-10000	0	-0.21	6	6
RELA	0.026	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.026	0.004	-10000	0	-10000	0	0
MYD88	0.026	0.005	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.049	0.029	0.18	21	-10000	0	21
IL1RAP	0.023	0.031	-10000	0	-0.31	4	4
UBE2N	0.026	0.006	-10000	0	-10000	0	0
IRAK/TRAF6	0.004	0.065	-10000	0	-0.16	49	49
CASP1	0.016	0.056	-10000	0	-0.31	14	14
IL1RN/IL1R2	-0.016	0.11	0.14	6	-0.22	106	112
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.076	0.2	1	-0.17	55	56
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.023	0.042	-10000	0	-0.27	4	4
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
IL1RN	0.016	0.067	0.17	7	-0.31	19	26
TRAF6/TAK1/TAB1/TAB2	0.031	0.017	-10000	0	-10000	0	0
MAP2K6	0.007	0.055	0.2	30	-0.14	1	31

×

Ceramide signaling pathway

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
SPHK2	-0.011	0.004	-10000	0	-10000	0	0
MAP4K4	0	0.051	-10000	0	-0.29	4	4
BAG4	0.008	0.063	-10000	0	-0.31	18	18
PKC zeta/ceramide	0.003	0.07	-10000	0	-0.2	41	41
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	0.025	0.025	0.17	3	-0.31	2	5
BAX	-0.001	0.059	-10000	0	-0.34	12	12
RIPK1	0.026	0.005	-10000	0	-10000	0	0
AKT1	0.005	0.1	0.73	10	-10000	0	10
BAD	-0.011	0.071	0.19	11	-0.2	37	48
SMPD1	0.016	0.061	0.2	22	-0.17	3	25
RB1	-0.016	0.062	-10000	0	-0.19	41	41
FADD/Caspase 8	0.006	0.055	0.21	5	-0.3	4	9
MAP2K4	-0.017	0.061	0.17	2	-0.19	38	40
NSMAF	0.022	0.01	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.019	0.071	0.17	9	-0.19	46	55
EGF	0.023	0.084	0.17	40	-0.31	23	63
mol:ceramide	-0.014	0.069	-10000	0	-0.2	42	42
MADD	0.026	0.006	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.008	0.006	-10000	0	-10000	0	0
ASAH1	0.019	0.012	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.016	0.062	-10000	0	-0.19	41	41
cell proliferation	-0.001	0.079	0.22	3	-0.2	37	40
BID	0.005	0.11	-10000	0	-0.63	11	11
MAP3K1	-0.016	0.064	0.19	1	-0.19	40	41
EIF2A	-0.008	0.071	0.18	26	-0.2	29	55
TRADD	0.024	0.009	-10000	0	-10000	0	0
CRADD	0.026	0.006	-10000	0	-10000	0	0
MAPK3	-0.017	0.07	0.19	9	-0.2	35	44
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.018	0.072	0.19	9	-0.21	31	40
Cathepsin D/ceramide	0.004	0.069	-10000	0	-0.2	38	38
FADD	0.002	0.054	0.2	5	-0.29	4	9
KSR1	-0.022	0.073	0.19	1	-0.2	55	56
MAPK8	-0.012	0.075	-10000	0	-0.22	32	32
PRKRA	-0.015	0.062	0.19	2	-0.19	40	42
PDGFA	0.025	0.008	-10000	0	-10000	0	0
TRAF2	0.026	0.006	-10000	0	-10000	0	0
IGF1	0.008	0.089	0.17	17	-0.31	33	50
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.014	0.069	-10000	0	-0.2	42	42
CTSD	0.027	0.004	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.038	0.01	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0	0.085	0.24	3	-0.21	37	40
PRKCD	0.026	0.005	-10000	0	-10000	0	0
PRKCZ	0.027	0.004	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.008	0.006	-10000	0	-10000	0	0
RelA/NF kappa B1	0.038	0.01	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.026	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.008	0.047	-10000	0	-0.3	4	4
TNFR1A/BAG4/TNF-alpha	0.022	0.068	-10000	0	-0.18	41	41
mol:Sphingosine-1-phosphate	-0.011	0.004	-10000	0	-10000	0	0
MAP2K1	-0.021	0.069	0.17	9	-0.2	36	45
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
CYCS	0.015	0.055	0.14	16	-0.21	10	26
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.02	0.049	-10000	0	-0.21	18	18
EIF2AK2	-0.017	0.059	0.18	3	-0.19	36	39
TNF-alpha/TNFR1A/FAN	0.033	0.055	-10000	0	-0.18	24	24
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.037	-10000	0	-10000	0	0
MAP2K2	-0.021	0.071	0.2	9	-0.2	38	47
SMPD3	-0.002	0.083	0.22	3	-0.29	26	29
TNF	0.014	0.076	0.17	12	-0.31	24	36
PKC zeta/PAR4	0.038	0.009	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.005	0.062	0.17	21	-0.16	34	55
NF kappa B1/RelA/I kappa B alpha	0.072	0.026	-10000	0	-10000	0	0
AIFM1	0.008	0.06	0.14	13	-0.21	11	24
BCL2	0.016	0.052	-10000	0	-0.31	12	12

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.026	0.08	0.22	3	-0.35	14	17
Syndecan-4/Syndesmos	0.037	0.12	0.36	3	-0.61	10	13
positive regulation of JNK cascade	0.039	0.12	0.31	2	-0.5	14	16
Syndecan-4/ADAM12	0.039	0.12	0.3	2	-0.55	13	15
CCL5	0.021	0.055	0.17	7	-0.31	12	19
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
DNM2	0.027	0.003	-10000	0	-10000	0	0
ITGA5	0.018	0.054	0.17	1	-0.31	13	14
SDCBP	0.022	0.01	-10000	0	-10000	0	0
PLG	0.025	0.038	0.17	23	-0.1	3	26
ADAM12	0.029	0.043	0.17	20	-0.31	4	24
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.049	0.025	-10000	0	-0.098	9	9
Syndecan-4/Laminin alpha1	0.033	0.12	0.34	4	-0.54	14	18
Syndecan-4/CXCL12/CXCR4	0.041	0.13	0.33	2	-0.54	14	16
Syndecan-4/Laminin alpha3	0.028	0.13	0.28	1	-0.5	17	18
MDK	0.031	0.027	0.17	16	-10000	0	16
Syndecan-4/FZD7	0.035	0.13	0.34	4	-0.49	18	22
Syndecan-4/Midkine	0.041	0.12	0.35	3	-0.58	11	14
FZD7	0.015	0.061	-10000	0	-0.31	17	17
Syndecan-4/FGFR1/FGF	0.029	0.12	-10000	0	-0.49	16	16
THBS1	0.016	0.063	0.17	5	-0.31	17	22
integrin-mediated signaling pathway	0.032	0.12	0.32	5	-0.45	17	22
positive regulation of MAPKKK cascade	0.039	0.12	0.31	2	-0.5	14	16
Syndecan-4/TACI	0.042	0.13	0.34	5	-0.55	13	18
CXCR4	0.025	0.032	0.17	6	-0.31	3	9
cell adhesion	0.004	0.062	0.19	7	-0.28	16	23
Syndecan-4/Dynamin	0.038	0.12	0.36	3	-0.57	12	15
Syndecan-4/TSP1	0.035	0.12	0.39	2	-0.51	14	16
Syndecan-4/GIPC	0.037	0.12	0.34	4	-0.55	13	17
Syndecan-4/RANTES	0.037	0.13	0.35	3	-0.51	16	19
ITGB1	0.026	0.004	-10000	0	-10000	0	0
LAMA1	0.02	0.07	0.17	22	-0.31	17	39
LAMA3	0	0.09	0.17	1	-0.31	38	39
RAC1	0.025	0.008	-10000	0	-10000	0	0
PRKCA	-0.011	0.12	0.73	9	-0.28	19	28
Syndecan-4/alpha-Actinin	0.036	0.12	0.34	4	-0.53	14	18
TFPI	0.023	0.056	0.17	15	-0.31	11	26
F2	0.032	0.038	0.17	26	-0.14	1	27
alpha5/beta1 Integrin	0.032	0.042	0.14	1	-0.21	13	14
positive regulation of cell adhesion	0.016	0.12	0.27	3	-0.52	16	19
ACTN1	0.022	0.037	-10000	0	-0.31	6	6
TNC	0.009	0.074	-10000	0	-0.31	25	25
Syndecan-4/CXCL12	0.034	0.12	0.32	2	-0.55	13	15
FGF6	0.018	0.011	0.17	2	-10000	0	2
RHOA	0.026	0.005	-10000	0	-10000	0	0
CXCL12	0.015	0.062	0.17	1	-0.31	17	18
TNFRSF13B	0.034	0.055	0.17	42	-0.31	5	47
FGF2	0.005	0.082	0.17	1	-0.31	31	32
FGFR1	0.02	0.019	-10000	0	-0.31	1	1
Syndecan-4/PI-4-5-P2	0.018	0.12	0.29	4	-0.54	13	17
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.018	0.05	0.17	4	-0.27	12	16
cell migration	-0.027	0.015	-10000	0	-10000	0	0
PRKCD	0.024	0.019	-10000	0	-0.17	1	1
vasculogenesis	0.035	0.12	0.32	4	-0.48	15	19
SDC4	0.023	0.12	0.32	4	-0.58	13	17
Syndecan-4/Tenascin C	0.032	0.12	0.36	3	-0.49	16	19
Syndecan-4/PI-4-5-P2/PKC alpha	-0.039	0.02	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.031	0.11	0.33	1	-0.56	10	11
MMP9	0.098	0.084	0.17	259	-0.31	5	264
Rac1/GTP	0.004	0.063	0.2	7	-0.28	16	23
cytoskeleton organization	0.037	0.12	0.36	3	-0.58	10	13
GIPC1	0.027	0.003	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.038	0.13	0.4	3	-0.5	16	19

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.027	0.003	-10000	0	-10000	0	0
PTK2	0.022	0.011	-10000	0	-10000	0	0
CRKL	-0.001	0.052	0.13	2	-0.19	29	31
GRB2/SOS1/SHC	0.049	0.018	-10000	0	-10000	0	0
HRAS	0.028	0.017	0.17	6	-10000	0	6
IRS1/Crk	0.008	0.056	-10000	0	-0.19	32	32
IGF-1R heterotetramer/IGF1/PTP1B	0.038	0.061	0.25	1	-0.18	29	30
AKT1	-0.013	0.069	0.18	26	-0.28	8	34
BAD	-0.017	0.064	0.17	24	-0.27	7	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.002	0.05	-10000	0	-0.19	28	28
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.016	0.063	0.22	1	-0.2	32	33
RAF1	0.004	0.073	0.28	3	-0.4	6	9
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.043	0.069	0.24	1	-0.18	32	33
YWHAZ	0.021	0.011	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.019	0.066	0.14	15	-0.18	40	55
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
RPS6KB1	-0.014	0.07	0.18	27	-0.28	8	35
GNB2L1	0.028	0.014	0.17	4	-10000	0	4
positive regulation of MAPKKK cascade	0.009	0.081	0.29	13	-0.34	4	17
PXN	0.026	0.006	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
HRAS/GTP	0.018	0.053	-10000	0	-0.17	28	28
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.059	0.063	0.26	1	-0.15	29	30
IGF-1R heterotetramer	0.022	0.027	0.2	1	-0.067	32	33
IGF-1R heterotetramer/IGF1/IRS/Nck	0.034	0.066	0.24	1	-0.19	31	32
Crk/p130 Cas/Paxillin	0.033	0.063	0.23	1	-0.17	31	32
IGF1R	0.022	0.027	0.2	1	-0.067	32	33
IGF1	0.026	0.057	0.2	17	-0.36	7	24
IRS2/Crk	0.008	0.056	0.16	3	-0.19	30	33
PI3K	0.037	0.072	0.24	1	-0.19	33	34
apoptosis	0.016	0.048	0.22	5	-0.17	2	7
HRAS/GDP	0.021	0.012	0.12	6	-10000	0	6
PRKCD	-0.006	0.08	0.19	2	-0.29	31	33
RAF1/14-3-3 E	0.023	0.074	0.28	7	-0.34	6	13
BAD/14-3-3	-0.017	0.05	0.18	2	-0.23	5	7
PRKCZ	-0.014	0.069	0.18	25	-0.28	8	33
Crk/p130 Cas/Paxillin/FAK1	0.016	0.052	0.15	2	-0.27	4	6
PTPN1	0.026	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.004	0.084	-10000	0	-0.3	33	33
BCAR1	0.022	0.011	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.047	0.058	0.25	1	-0.16	26	27
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.026	0.005	-10000	0	-10000	0	0
IRS1/NCK2	0.018	0.06	0.15	2	-0.19	31	33
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	-0.002	0.054	-10000	0	-0.2	31	31
IRS1	0.003	0.06	0.12	19	-0.21	31	50
IRS2	-0.002	0.054	0.13	2	-0.2	30	32
IGF-1R heterotetramer/IGF1	0.023	0.075	0.21	3	-0.24	32	35
GRB2	0.026	0.005	-10000	0	-10000	0	0
PDPK1	-0.016	0.064	0.18	17	-0.29	8	25
YWHAE	0.025	0.007	-10000	0	-10000	0	0
PRKD1	-0.006	0.081	0.19	2	-0.29	32	34
SHC1	0.026	0.006	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.066	0.15	0.17	1	-0.31	137	138
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.028	0.018	0.17	7	-10000	0	7
TCEB1	0.021	0.011	-10000	0	-10000	0	0
HIF1A/p53	0.01	0.067	0.23	4	-0.24	27	31
HIF1A	-0.007	0.062	-10000	0	-0.26	26	26
COPS5	0.022	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.061	0.039	-10000	0	-0.19	1	1
FIH (dimer)	0.025	0.007	-10000	0	-10000	0	0
CDKN2A	0.056	0.06	0.17	100	-10000	0	100
ARNT/IPAS	-0.028	0.11	-10000	0	-0.21	128	128
HIF1AN	0.025	0.007	-10000	0	-10000	0	0
GNB2L1	0.028	0.014	0.17	4	-10000	0	4
HIF1A/ARNT	0.009	0.065	0.2	3	-0.25	25	28
CUL2	0.026	0.004	-10000	0	-10000	0	0
OS9	0.027	0.004	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.044	0.028	0.24	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.009	0.067	-10000	0	-0.25	27	27
PHD1-3/OS9	0.06	0.035	-10000	0	-0.16	8	8
HIF1A/RACK1/Elongin B/Elongin C	0.026	0.066	0.21	2	-0.24	21	23
VHL	0.025	0.016	-10000	0	-0.31	1	1
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	0.005	0.061	-10000	0	-0.25	24	24
EGLN3	0.02	0.045	-10000	0	-0.31	9	9
EGLN2	0.027	0.004	-10000	0	-10000	0	0
EGLN1	0.026	0.006	-10000	0	-10000	0	0
TP53	0.023	0.01	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.021	0.082	-10000	0	-0.46	13	13
ARNT	0.026	0.006	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.027	0.003	-10000	0	-10000	0	0
HIF1A/p19ARF	0.028	0.084	0.19	17	-0.26	26	43

×

HIF-2-alpha transcription factor network

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
MMP14	0.014	0.15	-10000	0	-0.83	13	13
oxygen homeostasis	0	0.01	-10000	0	-0.098	1	1
TCEB2	0.028	0.018	0.17	7	-10000	0	7
TCEB1	0.021	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.026	0.078	0.28	1	-0.28	4	5
EPO	-0.015	0.2	0.31	1	-0.47	56	57
FIH (dimer)	0.018	0.024	-10000	0	-0.11	1	1
APEX1	0.02	0.028	-10000	0	-10000	0	0
SERPINE1	0.006	0.17	0.33	8	-0.45	31	39
FLT1	-0.006	0.19	-10000	0	-0.78	22	22
ADORA2A	-0.006	0.15	0.31	7	-0.43	27	34
germ cell development	0.002	0.17	0.35	5	-0.43	40	45
SLC11A2	0.004	0.15	0.29	3	-0.44	27	30
BHLHE40	0.004	0.16	0.35	4	-0.48	26	30
HIF1AN	0.018	0.024	-10000	0	-0.11	1	1
HIF2A/ARNT/SIRT1	0.02	0.12	0.29	1	-0.3	21	22
ETS1	0.026	0.042	0.18	1	-0.25	7	8
CITED2	0.022	0.079	-10000	0	-0.51	9	9
KDR	-0.023	0.25	-10000	0	-0.94	31	31
PGK1	0.007	0.16	0.33	6	-0.44	27	33
SIRT1	0.024	0.01	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.049	0.2	-10000	0	-0.49	27	27
EPAS1	0.002	0.068	-10000	0	-0.22	15	15
SP1	0.028	0.016	-10000	0	-0.099	7	7
ABCG2	-0.01	0.19	0.34	5	-0.48	49	54
EFNA1	0.002	0.15	0.29	1	-0.45	23	24
FXN	-0.008	0.15	0.32	7	-0.43	27	34
POU5F1	0.001	0.17	0.35	5	-0.44	40	45
neuron apoptosis	-0.048	0.19	0.48	27	-10000	0	27
EP300	0.025	0.026	-10000	0	-0.31	3	3
EGLN3	0.013	0.05	-10000	0	-0.31	9	9
EGLN2	0.019	0.025	-10000	0	-0.11	1	1
EGLN1	0.018	0.025	-10000	0	-0.11	1	1
VHL/Elongin B/Elongin C	0.042	0.028	-10000	0	-0.21	1	1
VHL	0.025	0.016	-10000	0	-0.31	1	1
ARNT	0.018	0.028	-10000	0	-10000	0	0
SLC2A1	-0.006	0.15	0.32	8	-0.43	27	35
TWIST1	0	0.16	0.32	9	-0.43	30	39
ELK1	0.031	0.003	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.032	0.12	0.3	1	-0.32	11	12
VEGFA	-0.003	0.17	0.33	6	-0.43	44	50
CREBBP	0.026	0.005	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.019	0.01	-10000	0	-10000	0	0
epithelial cell differentiation	0.047	0.023	-10000	0	-10000	0	0
CYFIP2	0.026	0.005	-10000	0	-10000	0	0
ENAH	-0.009	0.088	0.38	15	-10000	0	15
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
EPHA2	-0.002	0.096	0.17	3	-0.31	43	46
MYO6	0.007	0.055	0.19	24	-10000	0	24
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.051	0.015	-10000	0	-10000	0	0
AQP5	-0.14	0.19	-10000	0	-0.39	181	181
CTNND1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.001	0.052	0.19	29	-10000	0	29
regulation of calcium-dependent cell-cell adhesion	-0.004	0.058	0.2	29	-10000	0	29
EGF	0.023	0.084	0.17	40	-0.31	23	63
NCKAP1	0.026	0.005	-10000	0	-10000	0	0
AQP3	0.002	0.071	0.34	2	-0.37	14	16
cortical microtubule organization	0.047	0.023	-10000	0	-10000	0	0
GO:0000145	-0.002	0.049	0.18	29	-10000	0	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.052	0.026	-10000	0	-10000	0	0
MLLT4	0.026	0.005	-10000	0	-10000	0	0
ARF6/GDP	-0.032	0.034	-10000	0	-10000	0	0
ARF6	0.027	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.043	0.066	-10000	0	-0.17	39	39
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.004	0.035	0.17	11	-10000	0	11
PVRL2	0.027	0.004	-10000	0	-10000	0	0
ZYX	-0.005	0.043	0.2	18	-10000	0	18
ARF6/GTP	0.048	0.067	-10000	0	-0.16	39	39
CDH1	0.024	0.009	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.022	0.068	-10000	0	-0.15	54	54
RhoA/GDP	0.048	0.024	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.013	0.041	0.16	19	-10000	0	19
IGF-1R heterotetramer	0.026	0.017	0.17	1	-0.31	1	2
GIT1	0.027	0.002	-10000	0	-10000	0	0
IGF1R	0.026	0.017	0.17	1	-0.31	1	2
IGF1	0.008	0.089	0.17	17	-0.31	33	50
DIAPH1	0.025	0.12	-10000	0	-0.49	16	16
Wnt receptor signaling pathway	-0.047	0.023	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.032	0.034	-10000	0	-10000	0	0
CTNNA1	0.026	0.006	-10000	0	-10000	0	0
VCL	-0.013	0.042	0.16	19	-0.16	1	20
EFNA1	0.026	0.006	-10000	0	-10000	0	0
LPP	-0.014	0.047	0.18	16	-10000	0	16
Ephrin A1/EPHA2	0.027	0.056	-10000	0	-0.15	30	30
SEC6/SEC8	-0.02	0.012	-10000	0	-10000	0	0
MGAT3	-0.004	0.058	0.2	29	-10000	0	29
HGF/MET	0.02	0.07	-10000	0	-0.18	45	45
HGF	0.011	0.075	0.17	9	-0.31	24	33
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.019	0.01	-10000	0	-10000	0	0
actin cable formation	0.016	0.11	0.31	42	-0.24	5	47
KIAA1543	-0.005	0.044	0.18	22	-10000	0	22
KIFC3	-0.006	0.044	0.19	21	-10000	0	21
NCK1	0.025	0.007	-10000	0	-10000	0	0
EXOC3	0.026	0.005	-10000	0	-10000	0	0
ACTN1	-0.004	0.048	0.19	23	-10000	0	23
NCK1/GIT1	0.037	0.011	-10000	0	-10000	0	0
mol:GDP	0.047	0.023	-10000	0	-10000	0	0
EXOC4	0.024	0.008	-10000	0	-10000	0	0
STX4	-0.002	0.051	0.2	26	-10000	0	26
PIP5K1C	-0.001	0.053	0.2	29	-10000	0	29
LIMA1	0.027	0.003	-10000	0	-10000	0	0
ABI1	0.027	0.004	-10000	0	-10000	0	0
ROCK1	-0.006	0.096	0.4	15	-10000	0	15
adherens junction assembly	-0.009	0.098	0.29	15	-0.47	9	24
IGF-1R heterotetramer/IGF1	0.032	0.048	0.16	1	-0.15	24	25
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.009	-10000	0	-10000	0	0
MET	-0.004	0.093	-10000	0	-0.31	42	42
PLEKHA7	-0.004	0.047	0.2	22	-10000	0	22
mol:GTP	0.041	0.065	-10000	0	-0.16	39	39
establishment of epithelial cell apical/basal polarity	0.005	0.091	0.32	26	-10000	0	26
cortical actin cytoskeleton stabilization	0.019	0.01	-10000	0	-10000	0	0
regulation of cell-cell adhesion	-0.013	0.041	0.16	19	-10000	0	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.019	0.01	-10000	0	-10000	0	0

×

Insulin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.018	0.078	-10000	0	-0.17	63	63
TC10/GTP	0.018	0.064	-10000	0	-0.15	54	54
Insulin Receptor/Insulin/IRS1/Shp2	0.056	0.048	-10000	0	-0.18	14	14
HRAS	0.028	0.017	0.17	6	-10000	0	6
APS homodimer	0.028	0.03	0.17	14	-0.31	1	15
GRB14	0.048	0.062	0.17	82	-0.31	3	85
FOXO3	-0.12	0.26	-10000	0	-0.56	126	126
AKT1	-0.011	0.079	0.24	19	-0.28	5	24
INSR	0.029	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.056	0.028	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.025	0.008	-10000	0	-10000	0	0
SORBS1	-0.022	0.12	-10000	0	-0.31	70	70
CRK	0.025	0.007	-10000	0	-10000	0	0
PTPN1	-0.007	0.021	0.15	8	-10000	0	8
CAV1	-0.031	0.057	0.2	4	-0.18	50	54
CBL/APS/CAP/Crk-II/C3G	0.038	0.08	-10000	0	-0.16	54	54
Insulin Receptor/Insulin/IRS1/NCK2	0.059	0.044	-10000	0	-0.17	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.049	-10000	0	-0.19	15	15
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.019	0.051	-10000	0	-0.32	4	4
RPS6KB1	-0.015	0.073	0.22	19	-0.27	5	24
PARD6A	0.025	0.018	0.17	5	-10000	0	5
CBL	0.025	0.016	-10000	0	-0.31	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.013	0.068	-10000	0	-0.59	6	6
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.022	0.061	0.18	4	-0.25	7	11
HRAS/GTP	-0.033	0.038	-10000	0	-0.17	29	29
Insulin Receptor	0.029	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.065	0.049	-10000	0	-0.16	13	13
PRKCI	0.021	0.051	-10000	0	-0.34	3	3
Insulin Receptor/Insulin/GRB14/PDK1	0.024	0.049	-10000	0	-0.2	16	16
SHC1	0.026	0.006	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.034	0.061	-10000	0	-0.45	6	6
PI3K	0.049	0.053	-10000	0	-0.2	14	14
NCK2	0.027	0.003	-10000	0	-10000	0	0
RHOQ	0.026	0.005	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
HRAS/GDP	0.021	0.012	0.12	6	-10000	0	6
AKT2	-0.012	0.076	0.24	15	-0.28	5	20
PRKCZ	0.022	0.049	-10000	0	-0.3	9	9
SH2B2	0.028	0.03	0.17	14	-0.31	1	15
SHC/SHIP	0.011	0.054	0.17	6	-0.18	29	35
F2RL2	0.076	0.074	0.17	173	-0.31	1	174
TRIP10	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.047	0.022	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.035	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.07	0.032	-10000	0	-10000	0	0
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0
RASA1	0.025	0.016	-10000	0	-0.31	1	1
NCK1	0.025	0.007	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.03	0.081	0.19	5	-0.17	59	64
TC10/GDP	0.02	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.058	0.03	-10000	0	-10000	0	0
INPP5D	-0.023	0.05	0.18	8	-0.18	29	37
SOS1	0.026	0.005	-10000	0	-10000	0	0
SGK1	-0.11	0.28	-10000	0	-0.77	76	76
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
IRS1	0.017	0.058	-10000	0	-0.31	15	15
p62DOK/RasGAP	0.035	0.061	-10000	0	-0.45	6	6
INS	0.024	0.026	0.19	12	-10000	0	12
mol:PI-3-4-P2	-0.023	0.05	0.18	8	-0.18	29	37
GRB2	0.026	0.005	-10000	0	-10000	0	0
EIF4EBP1	-0.019	0.059	0.21	11	-0.28	5	16
PTPRA	0.029	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
TC10/GTP/CIP4	0.035	0.008	-10000	0	-10000	0	0
PDPK1	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.017	0.037	-10000	0	-0.18	13	13
Insulin Receptor/Insulin/IRS1	0.043	0.04	-10000	0	-0.16	14	14
Insulin Receptor/Insulin/IRS3	0.038	0.021	0.15	12	-10000	0	12
Par3/Par6	0.073	0.061	0.23	2	-0.13	2	4

×

Caspase cascade in apoptosis

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.005	0.076	0.22	4	-0.32	16	20
ACTA1	-0.038	0.094	0.19	8	-0.35	23	31
NUMA1	0.007	0.073	0.22	4	-0.32	14	18
SPTAN1	-0.005	0.09	0.21	25	-0.34	17	42
LIMK1	0.001	0.097	0.21	41	-0.32	19	60
BIRC3	0.025	0.025	0.17	3	-0.31	2	5
BIRC2	0.026	0.006	-10000	0	-10000	0	0
BAX	0.027	0.01	0.17	2	-10000	0	2
CASP10	-0.025	0.053	0.22	3	-0.24	23	26
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.027	0.001	-10000	0	-10000	0	0
PTK2	0.001	0.077	0.21	4	-0.3	20	24
DIABLO	0.026	0.006	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.005	0.089	0.21	25	-0.34	17	42
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.026	0.006	-10000	0	-10000	0	0
GSN	-0.007	0.09	0.21	23	-0.35	17	40
MADD	0.026	0.006	-10000	0	-10000	0	0
TFAP2A	-0.003	0.16	-10000	0	-0.58	30	30
BID	-0.003	0.034	0.14	2	-0.17	17	19
MAP3K1	-0.034	0.12	-10000	0	-0.36	54	54
TRADD	0.024	0.009	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.01	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.012	0.088	0.24	11	-0.35	19	30
CASP9	0.027	0.003	-10000	0	-10000	0	0
DNA repair	0.003	0.047	0.21	13	-10000	0	13
neuron apoptosis	0.004	0.12	-10000	0	-0.63	16	16
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.001	0.084	0.25	7	-0.4	12	19
APAF1	0.026	0.006	-10000	0	-10000	0	0
CASP6	0.012	0.098	-10000	0	-0.85	4	4
TRAF2	0.026	0.006	-10000	0	-10000	0	0
ICAD/CAD	-0.015	0.085	0.26	9	-0.34	18	27
CASP7	-0.006	0.056	0.23	2	-0.23	8	10
KRT18	0.02	0.034	-10000	0	-0.48	1	1
apoptosis	-0.004	0.083	0.34	5	-0.37	12	17
DFFA	-0.015	0.083	0.23	6	-0.34	19	25
DFFB	-0.013	0.085	0.24	9	-0.35	18	27
PARP1	-0.003	0.048	-10000	0	-0.22	13	13
actin filament polymerization	-0.001	0.1	0.32	18	-0.22	39	57
TNF	0.014	0.076	0.17	12	-0.31	24	36
CYCS	0.004	0.039	0.18	6	-0.16	8	14
SATB1	0.01	0.1	0.37	4	-0.83	4	8
SLK	-0.013	0.084	0.26	8	-0.33	19	27
p15 BID/BAX	0.013	0.044	-10000	0	-0.24	7	7
CASP2	0.005	0.059	0.2	14	-0.27	6	20
JNK cascade	0.034	0.12	0.36	54	-10000	0	54
CASP3	-0.013	0.085	0.2	7	-0.34	21	28
LMNB2	0.019	0.097	0.27	12	-0.36	11	23
RIPK1	0.026	0.005	-10000	0	-10000	0	0
CASP4	0.025	0.016	-10000	0	-0.31	1	1
Mammalian IAPs/DIABLO	0.063	0.026	-10000	0	-0.17	2	2
negative regulation of DNA binding	-0.002	0.16	-10000	0	-0.57	30	30
stress fiber formation	-0.012	0.083	0.26	8	-0.33	19	27
GZMB	-0.023	0.055	0.26	2	-0.26	20	22
CASP1	0.004	0.047	-10000	0	-0.26	14	14
LMNB1	0.019	0.1	0.28	13	-0.4	9	22
APP	0.004	0.12	-10000	0	-0.64	16	16
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.006	0.002	-10000	0	-10000	0	0
VIM	-0.003	0.08	0.28	3	-0.37	13	16
LMNA	0.022	0.083	0.26	14	-0.31	8	22
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.006	0.05	-10000	0	-0.29	3	3
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.013	0.084	0.2	11	-0.34	19	30
APAF-1/Caspase 9	0.012	0.074	-10000	0	-0.62	6	6
nuclear fragmentation during apoptosis	0.007	0.072	0.22	4	-0.32	14	18
CFL2	0.001	0.1	0.22	39	-0.32	18	57
GAS2	-0.015	0.08	0.19	7	-0.33	19	26
positive regulation of apoptosis	0.024	0.096	0.27	16	-0.44	5	21
PRF1	0.022	0.045	0.17	4	-0.31	8	12

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.022	0.029	-10000	0	-0.31	3	3
HSPA8	0.026	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.034	0.062	-10000	0	-0.2	16	16
AKT1	0.027	0.008	-10000	0	-10000	0	0
GSC	0.034	0.11	0.9	1	-1.2	2	3
NKX2-5	0.001	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.026	0.069	0.27	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.074	0.054	-10000	0	-0.26	3	3
SMAD4	0.022	0.035	-10000	0	-0.15	4	4
CBFB	0.024	0.009	-10000	0	-10000	0	0
SAP18	0.026	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.008	0.093	-10000	0	-0.18	89	89
SMAD3/SMAD4/VDR	0.063	0.057	-10000	0	-0.19	3	3
MYC	0.027	0.034	0.17	24	-10000	0	24
CDKN2B	-0.023	0.13	-10000	0	-0.93	5	5
AP1	0.009	0.084	0.21	1	-0.3	11	12
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.007	0.075	-10000	0	-0.25	20	20
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.002	0.052	-10000	0	-0.34	1	1
SP3	0.027	0.006	-10000	0	-10000	0	0
CREB1	0.027	0.003	-10000	0	-10000	0	0
FOXH1	0.041	0.052	0.18	57	-0.19	1	58
SMAD3/SMAD4/GR	0.038	0.061	-10000	0	-0.21	12	12
GATA3	-0.07	0.15	-10000	0	-0.3	145	145
SKI/SIN3/HDAC complex/NCoR1	0.013	0.043	-10000	0	-0.18	1	1
MEF2C/TIF2	0.006	0.068	0.23	7	-0.3	3	10
endothelial cell migration	0.014	0.21	0.99	20	-10000	0	20
MAX	0.026	0.01	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
RBBP4	0.026	0.015	-10000	0	-0.31	1	1
RUNX2	0.026	0.023	0.17	1	-0.31	2	3
RUNX3	0.028	0.029	0.17	8	-0.31	2	10
RUNX1	0.025	0.018	0.17	1	-0.31	1	2
CTBP1	0.026	0.004	-10000	0	-10000	0	0
NR3C1	0.018	0.051	-10000	0	-0.31	11	11
VDR	0.024	0.035	0.17	2	-0.31	5	7
CDKN1A	0.01	0.11	-10000	0	-1	5	5
KAT2B	0.024	0.011	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.06	0.055	-10000	0	-0.3	1	1
DCP1A	0.026	0.005	-10000	0	-10000	0	0
SKI	0.027	0.004	-10000	0	-10000	0	0
SERPINE1	-0.015	0.22	-10000	0	-1	20	20
SMAD3/SMAD4/ATF2	0.028	0.071	-10000	0	-0.19	28	28
SMAD3/SMAD4/ATF3	0.025	0.093	0.2	2	-0.21	48	50
SAP30	0.026	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.045	0.032	0.18	1	-0.18	3	4
JUN	-0.005	0.075	-10000	0	-0.3	11	11
SMAD3/SMAD4/IRF7	0.048	0.052	-10000	0	-0.17	1	1
TFE3	0.028	0.017	-10000	0	-10000	0	0
COL1A2	0.019	0.055	-10000	0	-0.79	2	2
mesenchymal cell differentiation	-0.043	0.049	0.2	2	-10000	0	2
DLX1	0.15	0.054	0.17	423	-10000	0	423
TCF3	0.026	0.005	-10000	0	-10000	0	0
FOS	-0.016	0.12	0.19	4	-0.32	63	67
SMAD3/SMAD4/Max	0.043	0.049	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.048	0.027	-10000	0	-0.18	3	3
ZBTB17	0.026	0.004	-10000	0	-10000	0	0
LAMC1	0.012	0.033	0.2	3	-10000	0	3
TGIF2/HDAC complex/SMAD3/SMAD4	0.043	0.046	-10000	0	-10000	0	0
IRF7	0.034	0.031	0.17	23	-10000	0	23
ESR1	0.015	0.058	0.17	1	-0.31	15	16
HNF4A	0.029	0.035	0.17	27	-10000	0	27
MEF2C	0.032	0.075	0.2	62	-0.29	4	66
SMAD2-3/SMAD4	0.053	0.046	-10000	0	-0.26	1	1
Cbp/p300/Src-1	0.046	0.029	-10000	0	-0.18	3	3
IGHV3OR16-13	0.01	0.017	-10000	0	-0.33	1	1
TGIF2/HDAC complex	0.026	0.005	-10000	0	-10000	0	0
CREBBP	0.024	0.012	-10000	0	-10000	0	0
SKIL	0.021	0.042	0.17	3	-0.31	7	10
HDAC1	0.027	0.003	-10000	0	-10000	0	0
HDAC2	0.023	0.01	-10000	0	-10000	0	0
SNIP1	0.027	0.003	-10000	0	-10000	0	0
GCN5L2	-0.001	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.053	0.047	-10000	0	-0.17	2	2
MSG1/HSC70	-0.004	0.1	0.14	11	-0.21	89	100
SMAD2	0.028	0.018	-10000	0	-0.2	1	1
SMAD3	0.02	0.035	-10000	0	-0.13	5	5
SMAD3/E2F4-5/DP1/p107/SMAD4	0.012	0.049	0.17	6	-0.19	5	11
SMAD2/SMAD2/SMAD4	-0.003	0.055	0.22	2	-0.18	12	14
NCOR1	0.026	0.007	-10000	0	-10000	0	0
NCOA2	-0.015	0.1	-10000	0	-0.31	53	53
NCOA1	0.027	0.004	-10000	0	-10000	0	0
MYOD/E2A	0.033	0.029	-10000	0	-0.21	4	4
SMAD2-3/SMAD4/SP1/MIZ-1	0.084	0.057	-10000	0	-0.27	2	2
IFNB1	0.003	0.035	0.2	3	-10000	0	3
SMAD3/SMAD4/MEF2C	0.061	0.073	0.24	10	-0.32	3	13
CITED1	-0.033	0.14	0.17	12	-0.31	94	106
SMAD2-3/SMAD4/ARC105	0.067	0.046	-10000	0	-0.23	1	1
RBL1	0.008	0.076	-10000	0	-0.31	27	27
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.008	0.053	0.22	1	-0.32	4	5
RUNX1-3/PEBPB2	0.046	0.029	-10000	0	-0.17	3	3
SMAD7	0.014	0.087	-10000	0	-0.38	8	8
MYC/MIZ-1	0.034	0.029	0.14	1	-10000	0	1
SMAD3/SMAD4	-0.011	0.093	0.31	2	-0.39	18	20
IL10	-0.042	0.11	0.2	2	-0.36	22	24
PIASy/HDAC complex	0.027	0.008	-10000	0	-10000	0	0
PIAS3	0.025	0.01	-10000	0	-10000	0	0
CDK2	0.024	0.011	-10000	0	-10000	0	0
IL5	-0.039	0.092	0.19	2	-0.21	50	52
CDK4	0.024	0.012	-10000	0	-10000	0	0
PIAS4	0.027	0.008	-10000	0	-10000	0	0
ATF3	-0.003	0.11	0.17	24	-0.31	53	77
SMAD3/SMAD4/SP1	0.055	0.05	-10000	0	-0.23	4	4
FOXG1	0.004	0.048	0.17	32	-10000	0	32
FOXO3	0.01	0.006	-10000	0	-10000	0	0
FOXO1	0.01	0.007	-10000	0	-10000	0	0
FOXO4	0.012	0.006	-10000	0	-10000	0	0
heart looping	0.032	0.074	0.2	62	-0.28	4	66
CEBPB	0.027	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.11	0.085	0.2	2	-0.17	5	7
MYOD1	0.019	0.038	0.17	11	-0.31	4	15
SMAD3/SMAD4/HNF4	0.044	0.053	-10000	0	-0.17	1	1
SMAD3/SMAD4/GATA3	-0.017	0.12	-10000	0	-0.2	127	127
SnoN/SIN3/HDAC complex/NCoR1	0.021	0.042	0.17	3	-0.31	7	10
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.064	0.054	-10000	0	-0.17	2	2
SMAD3/SMAD4/SP1-3	0.068	0.053	-10000	0	-0.25	2	2
MED15	0.026	0.005	-10000	0	-10000	0	0
SP1	0.029	0.017	-10000	0	-0.13	4	4
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.06	0.054	0.22	1	-0.23	3	4
ITGB5	0.015	0.043	0.2	10	-0.28	1	11
TGIF/SIN3/HDAC complex/CtBP	0.014	0.041	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	0.023	0.079	-10000	0	-0.19	40	40
AR	-0.003	0.095	-10000	0	-0.31	43	43
negative regulation of cell growth	-0.001	0.069	0.18	1	-0.25	12	13
SMAD3/SMAD4/MYOD	0.039	0.054	-10000	0	-0.18	5	5
E2F5	0.022	0.013	0.17	1	-10000	0	1
E2F4	0.024	0.009	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.086	0.066	0.24	1	-0.19	3	4
SMAD2-3/SMAD4/FOXO1-3a-4	0.016	0.038	-10000	0	-0.32	4	4
TFDP1	0.025	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.028	0.093	-10000	0	-0.3	11	11
SMAD3/SMAD4/RUNX2	0.043	0.049	-10000	0	-0.2	2	2
TGIF2	0.026	0.005	-10000	0	-10000	0	0
TGIF1	0.025	0.007	-10000	0	-10000	0	0
ATF2	0.007	0.078	-10000	0	-0.31	28	28

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.025	0.017	-10000	0	-0.12	5	5
SVIL	0.014	0.064	-10000	0	-0.3	19	19
ZNF318	0.027	0.018	0.18	6	-10000	0	6
JMJD2C	0.003	0.009	-10000	0	-0.13	2	2
T-DHT/AR/Ubc9	0.015	0.065	-10000	0	-0.17	44	44
CARM1	0.026	0.008	-10000	0	-10000	0	0
PRDX1	0.027	0.003	-10000	0	-10000	0	0
PELP1	0.025	0.008	-10000	0	-10000	0	0
CTNNB1	0.026	0.012	-10000	0	-10000	0	0
AKT1	0.027	0.008	-10000	0	-10000	0	0
PTK2B	0.019	0.015	-10000	0	-10000	0	0
MED1	0.027	0.007	-10000	0	-10000	0	0
MAK	0.068	0.07	0.18	142	-10000	0	142
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.015	0.055	-10000	0	-0.29	14	14
GSN	0.023	0.029	-10000	0	-0.22	5	5
NCOA2	-0.015	0.1	-10000	0	-0.31	53	53
NCOA6	0.025	0.013	-10000	0	-10000	0	0
DNA-PK	0.045	0.028	0.21	5	-10000	0	5
NCOA4	0.026	0.007	-10000	0	-10000	0	0
PIAS3	0.025	0.012	-10000	0	-10000	0	0
cell proliferation	0.036	0.07	0.26	2	-0.4	6	8
XRCC5	0.027	0.006	-10000	0	-10000	0	0
UBE3A	0.026	0.016	-10000	0	-0.11	6	6
T-DHT/AR/SNURF	0.01	0.075	-10000	0	-0.19	54	54
FHL2	-0.014	0.16	-10000	0	-0.75	21	21
RANBP9	0.026	0.013	-10000	0	-0.1	2	2
JMJD1A	0.003	0.011	-10000	0	-0.082	6	6
CDK6	0.016	0.054	-10000	0	-0.31	13	13
TGFB1I1	0.001	0.088	-10000	0	-0.3	37	37
T-DHT/AR/CyclinD1	0.017	0.065	0.14	1	-0.17	43	44
XRCC6	0.027	0.006	-10000	0	-10000	0	0
T-DHT/AR	0.018	0.076	-10000	0	-0.16	70	70
CTDSP1	0.026	0.008	-10000	0	-10000	0	0
CTDSP2	0.027	0.013	0.13	6	-10000	0	6
BRCA1	0.025	0.015	0.17	1	-0.095	2	3
TCF4	0.022	0.029	-10000	0	-0.31	3	3
CDKN2A	0.056	0.061	0.18	100	-10000	0	100
SRF	0.023	0.037	-10000	0	-0.15	21	21
NKX3-1	-0.007	0.034	-10000	0	-0.095	48	48
KLK3	-0.013	0.16	-10000	0	-1.3	7	7
TMF1	0.026	0.008	-10000	0	-10000	0	0
HNRNPA1	0.027	0.009	0.13	1	-10000	0	1
AOF2	0	0.009	-10000	0	-0.076	7	7
APPL1	-0.011	0.014	0.11	6	-10000	0	6
T-DHT/AR/Caspase 8	0.016	0.065	-10000	0	-0.17	44	44
AR	-0.005	0.096	-10000	0	-0.3	43	43
UBA3	0.025	0.009	-10000	0	-10000	0	0
PATZ1	0.026	0.007	-10000	0	-10000	0	0
PAWR	0.026	0.008	-10000	0	-10000	0	0
PRKDC	0.023	0.014	0.21	1	-10000	0	1
PA2G4	0.027	0.01	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.016	0.059	-10000	0	-0.16	43	43
RPS6KA3	0.025	0.021	-10000	0	-0.12	8	8
T-DHT/AR/ARA70	0.016	0.065	-10000	0	-0.17	45	45
LATS2	0.026	0.009	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.016	0.06	0.15	2	-0.16	44	46
Cyclin D3/CDK11 p58	0.02	0.003	-10000	0	-10000	0	0
VAV3	-0.01	0.1	-10000	0	-0.3	54	54
KLK2	0.003	0.053	-10000	0	-0.67	2	2
CASP8	0.027	0.004	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.007	0.099	-10000	0	-0.25	55	55
TMPRSS2	-0.011	0.09	-10000	0	-0.42	19	19
CCND1	0.025	0.012	0.17	1	-10000	0	1
PIAS1	0.025	0.022	-10000	0	-0.17	4	4
mol:T-DHT	-0.001	0.018	-10000	0	-0.065	30	30
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	0.025	0.023	-10000	0	-0.16	7	7
T-DHT/AR/CDK6	0.01	0.071	-10000	0	-0.18	52	52
CMTM2	0.023	0.02	0.17	2	-0.31	1	3
SNURF	0.015	0.058	-10000	0	-0.31	15	15
ZMIZ1	0.021	0.031	-10000	0	-0.2	4	4
CCND3	0.027	0.004	-10000	0	-10000	0	0
TGIF1	0.025	0.009	0.13	1	-10000	0	1
FKBP4	0.024	0.015	-10000	0	-0.1	2	2

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.031	0.063	-10000	0	-0.34	3	3
epithelial cell differentiation	0.042	0.065	-10000	0	-0.32	1	1
ITCH	0.031	0.016	-10000	0	-10000	0	0
WWP1	0.028	0.079	-10000	0	-0.44	1	1
FYN	0.022	0.018	-10000	0	-0.31	1	1
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
PRL	0.02	0.014	0.17	4	-10000	0	4
neuron projection morphogenesis	0	0.094	0.26	26	-0.34	4	30
PTPRZ1	-0.072	0.16	0.17	12	-0.31	146	158
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.014	0.079	-10000	0	-0.34	5	5
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.007	0.068	-10000	0	-0.4	3	3
ADAM17	0.028	0.033	-10000	0	-0.3	4	4
ErbB4/ErbB4	0.019	0.063	-10000	0	-0.38	3	3
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.025	0.066	-10000	0	-0.35	4	4
NCOR1	0.025	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.002	0.068	-10000	0	-0.38	3	3
GRIN2B	-0.007	0.063	0.24	3	-0.36	3	6
ErbB4/ErbB2/betacellulin	0.02	0.078	0.25	1	-0.38	8	9
STAT1	0.029	0.019	0.17	8	-10000	0	8
HBEGF	0.027	0.027	0.17	6	-0.31	2	8
PRLR	0.018	0.077	0.17	22	-0.31	22	44
E4ICDs/ETO2	0.027	0.054	-10000	0	-0.36	2	2
axon guidance	0.024	0.062	-10000	0	-0.37	1	1
NEDD4	0.025	0.038	-10000	0	-0.29	6	6
Prolactin receptor/Prolactin receptor/Prolactin	0.027	0.056	0.14	7	-0.22	20	27
CBFA2T3	0.02	0.028	-10000	0	-0.31	3	3
ErbB4/ErbB2/HBEGF	0.029	0.058	0.25	1	-0.35	3	4
MAPK3	0.005	0.083	0.25	16	-0.34	4	20
STAT1 (dimer)	0.033	0.065	-10000	0	-0.34	3	3
MAPK1	0.006	0.082	0.24	15	-0.34	4	19
JAK2	0.026	0.016	-10000	0	-0.31	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.01	0.068	-10000	0	-0.43	3	3
NRG1	-0.032	0.07	-10000	0	-0.22	60	60
NRG3	0.009	0.083	0.17	18	-0.31	28	46
NRG2	-0.08	0.16	-10000	0	-0.31	155	155
NRG4	-0.076	0.16	0.17	8	-0.31	154	162
heart development	0.024	0.062	-10000	0	-0.37	1	1
neural crest cell migration	-0.009	0.067	-10000	0	-0.42	3	3
ERBB2	-0.007	0.033	0.27	1	-0.2	9	10
WWOX/E4ICDs	0.025	0.054	-10000	0	-0.38	2	2
SHC1	0.026	0.006	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.025	0.12	-10000	0	-0.35	22	22
apoptosis	-0.002	0.1	0.33	26	-10000	0	26
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.006	0.084	-10000	0	-0.3	23	23
ErbB4/ErbB2/epiregulin	0.024	0.069	0.24	1	-0.35	3	4
ErbB4/ErbB4/betacellulin/betacellulin	0.024	0.079	-10000	0	-0.32	13	13
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.052	0.082	-10000	0	-0.35	3	3
MDM2	0.017	0.07	0.34	11	-0.34	3	14
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.066	-10000	0	-0.33	3	3
STAT5A	0.03	0.07	0.34	2	-0.35	1	3
ErbB4/EGFR/neuregulin 1 beta	-0.012	0.088	-10000	0	-0.35	14	14
DLG4	0.017	0.045	-10000	0	-0.31	9	9
GRB2/SHC	0.037	0.011	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.026	0.055	-10000	0	-0.32	3	3
STAT5A (dimer)	0.059	0.078	0.31	1	-0.34	1	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.057	0.079	0.33	4	-0.35	1	5
LRIG1	0.026	0.005	-10000	0	-10000	0	0
EREG	0.013	0.08	0.17	19	-0.31	25	44
BTC	0.005	0.081	-10000	0	-0.31	31	31
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.016	0.055	-10000	0	-0.37	1	1
ERBB4	0.003	0.047	-10000	0	-0.38	3	3
STAT5B	0.026	0.005	-10000	0	-10000	0	0
YAP1	0.015	0.067	-10000	0	-0.51	6	6
GRB2	0.026	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.014	0.097	0.25	1	-0.37	7	8
glial cell differentiation	-0.025	0.054	0.32	3	-10000	0	3
WWOX	0.022	0.011	-10000	0	-10000	0	0
cell proliferation	-0.025	0.11	0.27	1	-0.5	12	13

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.027	0.01	0.17	2	-10000	0	2
alphaV beta3 Integrin	-0.009	0.098	-10000	0	-0.21	92	92
PTK2	-0.008	0.096	0.23	1	-0.38	22	23
positive regulation of JNK cascade	0.007	0.086	-10000	0	-0.29	26	26
CDC42/GDP	0.03	0.12	0.32	6	-0.37	30	36
Rac1/GDP	0.026	0.12	0.35	3	-0.37	26	29
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	0.017	0.11	-10000	0	-0.35	25	25
nectin-3/I-afadin	0.034	0.049	0.14	21	-0.21	14	35
RAPGEF1	0.002	0.12	0.31	7	-0.4	29	36
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.12	-10000	0	-0.44	30	30
PDGFB-D/PDGFRB	0.027	0.01	0.17	2	-10000	0	2
TLN1	-0.008	0.023	0.11	1	-0.12	16	17
Rap1/GTP	0.001	0.084	-10000	0	-0.3	29	29
IQGAP1	0.027	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.016	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.034	0.049	0.14	21	-0.21	14	35
PVR	0.027	0.003	-10000	0	-10000	0	0
Necl-5(dimer)	0.027	0.003	-10000	0	-10000	0	0
mol:GDP	0.018	0.14	0.34	6	-0.44	30	36
MLLT4	0.026	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
PI3K	0.059	0.062	-10000	0	-0.19	16	16
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.037	0.011	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.01	0.086	-10000	0	-0.29	27	27
PVRL1	0.026	0.006	-10000	0	-10000	0	0
PVRL3	0.023	0.065	0.17	23	-0.31	14	37
PVRL2	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
CDH1	0.024	0.009	-10000	0	-10000	0	0
CLDN1	-0.011	0.1	0.17	1	-0.31	53	54
JAM-A/CLDN1	0.032	0.083	0.19	1	-0.17	61	62
SRC	-0.003	0.13	-10000	0	-0.48	30	30
ITGB3	-0.037	0.13	-10000	0	-0.31	92	92
nectin-1(dimer)/I-afadin/I-afadin	0.037	0.011	-10000	0	-10000	0	0
FARP2	0.013	0.14	0.33	1	-0.47	24	25
RAC1	0.025	0.008	-10000	0	-10000	0	0
CTNNA1	0.026	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.048	0.046	-10000	0	-0.18	14	14
nectin-1/I-afadin	0.037	0.011	-10000	0	-10000	0	0
nectin-2/I-afadin	0.038	0.009	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.033	0.011	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.045	0.046	-10000	0	-0.18	14	14
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.006	-10000	0	-10000	0	0
F11R	0.026	0.006	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.007	0.086	-10000	0	-0.29	26	26
alphaV/beta3 Integrin/Talin	-0.002	0.084	0.21	12	-0.23	18	30
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.009	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.009	-10000	0	-10000	0	0
PIP5K1C	0.001	0.022	0.12	1	-0.12	14	15
VAV2	0.015	0.14	-10000	0	-0.46	25	25
RAP1/GDP	0.028	0.11	0.31	2	-0.34	30	32
ITGAV	0.026	0.005	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.048	0.046	-10000	0	-0.18	14	14
nectin-3(dimer)/I-afadin/I-afadin	0.034	0.049	0.14	21	-0.21	14	35
Rac1/GTP	0.016	0.11	-10000	0	-0.35	27	27
PTPRM	0.008	0.026	0.13	1	-0.14	14	15
E-cadherin/beta catenin/alpha catenin	0.061	0.035	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.027	0.003	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.013	0.027	0.25	3	-10000	0	3
TP53	-0.003	0.045	-10000	0	-0.17	31	31
Senescence	-0.003	0.045	-10000	0	-0.17	31	31
Apoptosis	-0.003	0.045	-10000	0	-0.17	31	31
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.001	0.063	0.3	20	-0.17	2	22
MDM4	0.026	0.005	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0.023	0.022	-10000	0	-10000	0	0
CDKN2C	0.031	0.018	0.16	3	-0.095	1	4
CDKN2A	0.058	0.06	0.18	99	-0.14	1	100
CCND2	-0.009	0.02	-10000	0	-0.14	4	4
RB1	0.005	0.019	0.14	4	-10000	0	4
CDK4	-0.007	0.014	-10000	0	-0.18	2	2
CDK6	-0.01	0.029	-10000	0	-0.17	12	12
G1/S progression	-0.005	0.019	-10000	0	-0.16	3	3

×

VEGFR1 specific signals

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.025	0.046	-10000	0	-0.39	5	5
VEGFR1 homodimer/NRP1	0.007	0.043	-10000	0	-0.38	5	5
mol:DAG	-0.03	0.063	0.19	6	-0.4	4	10
VEGFR1 homodimer/NRP1/VEGFR 121	0.015	0.061	0.17	1	-0.21	24	25
CaM/Ca2+	0.003	0.07	0.18	6	-0.38	4	10
HIF1A	0.028	0.032	-10000	0	-0.28	5	5
GAB1	0.026	0.016	-10000	0	-0.31	1	1
AKT1	-0.025	0.076	0.29	2	-0.36	7	9
PLCG1	-0.03	0.064	0.19	6	-0.41	4	10
NOS3	-0.004	0.08	0.28	9	-0.45	3	12
CBL	0.025	0.016	-10000	0	-0.31	1	1
mol:NO	0	0.09	0.32	13	-0.44	4	17
FLT1	0.011	0.048	-10000	0	-0.49	4	4
PGF	-0.011	0.11	0.17	2	-0.31	56	58
VEGFR1 homodimer/NRP2/VEGFR121	0.018	0.082	-10000	0	-0.2	51	51
CALM1	0.026	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
eNOS/Hsp90	0.011	0.084	0.28	7	-0.42	4	11
endothelial cell proliferation	-0.053	0.13	0.34	3	-0.39	45	48
mol:Ca2+	-0.029	0.063	0.19	6	-0.4	4	10
MAPK3	-0.034	0.072	0.22	7	-0.34	11	18
MAPK1	-0.033	0.073	0.23	8	-0.34	11	19
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
PLGF homodimer	-0.011	0.11	0.17	2	-0.31	56	58
PRKACA	0.027	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.013	0.1	-10000	0	-0.31	55	55
VEGFA homodimer	0.01	0.077	0.17	5	-0.31	26	31
VEGFR1 homodimer/VEGFA homodimer	0.016	0.067	0.19	1	-0.23	24	25
platelet activating factor biosynthetic process	-0.036	0.067	0.18	6	-0.35	10	16
PI3K	0.023	0.081	-10000	0	-0.34	7	7
PRKCA	-0.034	0.073	0.21	6	-0.36	11	17
PRKCB	-0.055	0.091	0.18	4	-0.3	38	42
VEGFR1 homodimer/PLGF homodimer	0.002	0.078	-10000	0	-0.2	58	58
VEGFA	0.01	0.077	0.17	5	-0.31	26	31
VEGFB	0.026	0.005	-10000	0	-10000	0	0
mol:IP3	-0.03	0.063	0.19	6	-0.4	4	10
RASA1	-0.012	0.047	0.19	10	-0.4	4	14
NRP2	0.005	0.083	-10000	0	-0.31	32	32
VEGFR1 homodimer	0.011	0.048	-10000	0	-0.49	4	4
VEGFB homodimer	0.026	0.005	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.001	0.099	0.38	5	-0.32	21	26
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
mol:PI-3-4-5-P3	0.022	0.079	-10000	0	-0.34	7	7
mol:L-citrulline	0	0.09	0.32	13	-0.44	4	17
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.042	0.068	-10000	0	-0.22	21	21
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.028	0.066	-10000	0	-0.22	24	24
CD2AP	0.027	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.032	0.084	-10000	0	-0.33	7	7
PDPK1	-0.023	0.073	0.27	5	-0.35	6	11
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.067	-10000	0	-0.22	23	23
mol:NADP	0	0.09	0.32	13	-0.44	4	17
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.04	0.067	-10000	0	-0.22	21	21
VEGFR1 homodimer/NRP2	0.012	0.067	-10000	0	-0.22	32	32

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.004	-10000	0	-10000	0	0
SPHK1	0.03	0.025	0.17	14	-10000	0	14
GNAI2	0.026	0.005	-10000	0	-10000	0	0
mol:S1P	0.013	0.011	0.16	2	-10000	0	2
GNAO1	-0.024	0.12	-10000	0	-0.31	71	71
mol:Sphinganine-1-P	-0.012	0.015	0.26	1	-10000	0	1
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.051	0.03	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
G12/G13	0.035	0.013	-10000	0	-10000	0	0
S1PR3	0.015	0.06	0.17	1	-0.31	16	17
S1PR2	0.027	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.007	0.016	-10000	0	-10000	0	0
S1PR5	-0.026	0.12	-10000	0	-0.31	78	78
S1PR4	0.031	0.033	0.17	20	-0.31	1	21
GNAI1	0.023	0.028	0.17	1	-0.31	3	4
S1P/S1P5/G12	0.014	0.069	0.17	2	-0.15	63	65
S1P/S1P3/Gq	0.009	0.075	-10000	0	-0.39	9	9
S1P/S1P4/Gi	-0.014	0.11	0.2	3	-0.26	68	71
GNAQ	0.026	0.006	-10000	0	-10000	0	0
GNAZ	-0.002	0.094	-10000	0	-0.31	42	42
GNA14	0.025	0.016	-10000	0	-0.31	1	1
GNA15	0.012	0.068	-10000	0	-0.31	21	21
GNA12	0.024	0.008	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
GNA11	0.016	0.058	-10000	0	-0.31	15	15
ABCC1	0.026	0.005	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.018	0.054	0.17	1	-0.31	13	14
ANTXR2	0.02	0.047	-10000	0	-0.31	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.009	-10000	0	-0.045	21	21
monocyte activation	-0.012	0.11	-10000	0	-0.34	46	46
MAP2K2	0.006	0.074	-10000	0	-0.56	8	8
MAP2K1	-0.007	0.008	-10000	0	-0.07	1	1
MAP2K7	-0.007	0.008	-10000	0	-0.07	1	1
MAP2K6	-0.007	0.014	0.14	1	-0.12	3	4
CYAA	-0.014	0.03	-10000	0	-0.15	21	21
MAP2K4	-0.006	0.008	-10000	0	-0.07	1	1
IL1B	-0.021	0.055	0.15	3	-0.17	47	50
Channel	0.025	0.041	0.12	1	-0.16	21	22
NLRP1	-0.009	0.023	-10000	0	-0.15	11	11
CALM1	0.026	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.003	0.055	-10000	0	-0.41	8	8
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.009	0.045	21	-10000	0	21
MAPK3	-0.007	0.008	-10000	0	-0.07	1	1
MAPK1	-0.007	0.008	-10000	0	-0.07	1	1
PGR	-0.023	0.048	-10000	0	-0.16	57	57
PA/Cellular Receptors	0.026	0.046	0.13	1	-0.18	21	22
apoptosis	-0.003	0.009	-10000	0	-0.045	21	21
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.025	0.04	0.12	1	-0.16	21	22
macrophage activation	-0.009	0.012	0.14	2	-10000	0	2
TNF	0.014	0.076	0.17	12	-0.31	24	36
VCAM1	-0.011	0.11	-10000	0	-0.35	45	45
platelet activation	0.003	0.055	-10000	0	-0.41	8	8
MAPKKK cascade	0.003	0.02	0.082	2	-0.083	14	16
IL18	-0.012	0.042	0.11	2	-0.19	19	21
negative regulation of macrophage activation	-0.003	0.009	-10000	0	-0.045	21	21
LEF	-0.003	0.009	-10000	0	-0.045	21	21
CASP1	-0.005	0.027	-10000	0	-0.14	15	15
mol:cAMP	0.002	0.056	-10000	0	-0.42	8	8
necrosis	-0.003	0.009	-10000	0	-0.045	21	21
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.025	0.039	0.12	1	-0.15	21	22
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.003	-10000	0	-10000	0	0
HDAC2	0.024	0.01	-10000	0	-10000	0	0
GNB1/GNG2	0.044	0.031	-10000	0	-0.18	6	6
forebrain development	-0.041	0.13	0.3	2	-0.41	23	25
GNAO1	-0.026	0.12	-10000	0	-0.31	71	71
SMO/beta Arrestin2	0.022	0.027	-10000	0	-10000	0	0
SMO	0.015	0.02	-10000	0	-10000	0	0
ARRB2	0.023	0.01	-10000	0	-10000	0	0
GLI3/SPOP	0.031	0.085	0.28	9	-0.34	9	18
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
GSK3B	0.025	0.007	-10000	0	-10000	0	0
GNAI2	0.024	0.008	-10000	0	-10000	0	0
SIN3/HDAC complex	0.065	0.021	-10000	0	-10000	0	0
GNAI1	0.022	0.028	0.17	1	-0.31	3	4
XPO1	0.014	0.024	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.044	0.13	-10000	0	-0.43	21	21
SAP30	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	0.015	0.02	-10000	0	-10000	0	0
MIM/GLI2A	-0.007	0.06	-10000	0	-0.12	105	105
IFT88	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.025	0.006	-10000	0	-10000	0	0
GLI2	0.012	0.054	0.22	6	-0.23	4	10
GLI3	0.017	0.086	0.28	9	-0.34	10	19
CSNK1D	0.026	0.005	-10000	0	-10000	0	0
CSNK1E	0.027	0.003	-10000	0	-10000	0	0
SAP18	0.026	0.006	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.006	-10000	0	-10000	0	0
GNG2	0.023	0.037	-10000	0	-0.31	6	6
Gi family/GTP	-0.029	0.11	-10000	0	-0.27	70	70
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.016	0.072	0.28	4	-0.32	11	15
GLI2/Su(fu)	0.015	0.046	-10000	0	-0.25	4	4
FOXA2	-0.22	0.41	-10000	0	-0.87	139	139
neural tube patterning	-0.041	0.13	0.3	2	-0.41	23	25
SPOP	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.022	0.047	-10000	0	-10000	0	0
GNB1	0.027	0.004	-10000	0	-10000	0	0
CSNK1G2	0.026	0.005	-10000	0	-10000	0	0
CSNK1G3	0.026	0.006	-10000	0	-10000	0	0
MTSS1	-0.007	0.06	-10000	0	-0.12	105	105
embryonic limb morphogenesis	-0.041	0.13	0.3	2	-0.41	23	25
SUFU	0.012	0.014	-10000	0	-10000	0	0
LGALS3	0.003	0.086	-10000	0	-0.31	35	35
catabolic process	0.034	0.096	0.32	7	-0.36	10	17
GLI3A/CBP	0.024	0.036	-10000	0	-0.33	4	4
KIF3A	0.026	0.005	-10000	0	-10000	0	0
GLI1	-0.042	0.14	0.3	2	-0.42	23	25
RAB23	0.025	0.022	-10000	0	-0.31	2	2
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
IFT172	0.027	0.003	-10000	0	-10000	0	0
RBBP7	0.027	0.005	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.01	0.063	-10000	0	-0.18	14	14
GNAZ	-0.004	0.094	-10000	0	-0.31	42	42
RBBP4	0.026	0.015	-10000	0	-0.31	1	1
CSNK1G1	0.027	0.003	-10000	0	-10000	0	0
PIAS1	0.026	0.015	-10000	0	-0.31	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.024	0.055	0.25	2	-0.22	4	6
STK36	0.014	0.024	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.026	0.1	-10000	0	-0.32	40	40
PTCH1	-0.031	0.13	0.45	2	-0.47	8	10
MIM/GLI1	-0.069	0.19	-10000	0	-0.41	106	106
CREBBP	0.024	0.036	-10000	0	-0.33	4	4
Su(fu)/SIN3/HDAC complex	0.021	0.038	-10000	0	-0.26	2	2

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.006	0.053	-10000	0	-0.24	20	20
CRKL	0.026	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.006	-10000	0	-10000	0	0
DOCK1	0.023	0.03	-10000	0	-0.31	4	4
ITGA4	0.021	0.059	0.17	11	-0.31	13	24
alpha4/beta7 Integrin/MAdCAM1	0.063	0.076	0.25	3	-0.19	27	30
EPO	0.003	0.1	0.17	25	-0.31	42	67
alpha4/beta7 Integrin	0.026	0.067	0.18	10	-0.23	27	37
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.034	0.045	-10000	0	-0.21	13	13
EPO/EPOR (dimer)	0.022	0.078	0.15	33	-0.21	41	74
lamellipodium assembly	0.013	0.042	-10000	0	-0.32	2	2
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
PI3K	0.031	0.034	-10000	0	-0.24	6	6
ARF6	0.027	0.004	-10000	0	-10000	0	0
JAK2	0	0.067	0.16	2	-0.18	53	55
PXN	0.026	0.006	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
MADCAM1	0.053	0.06	0.17	92	-0.31	1	93
cell adhesion	0.06	0.074	0.24	3	-0.19	27	30
CRKL/CBL	0.037	0.015	-10000	0	-0.21	1	1
ITGB1	0.026	0.004	-10000	0	-10000	0	0
SRC	-0.02	0.038	0.18	6	-0.17	17	23
ITGB7	0.015	0.064	0.17	3	-0.31	18	21
RAC1	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.045	0.053	0.24	4	-0.19	17	21
p130Cas/Crk/Dock1	0.016	0.046	0.19	2	-0.28	3	5
VCAM1	0.025	0.039	0.17	8	-0.31	5	13
RHOA	0.026	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.057	0.045	-10000	0	-0.17	13	13
BCAR1	-0.019	0.032	0.18	3	-0.17	14	17
EPOR	0.03	0.021	0.17	10	-10000	0	10
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.025	0.016	-10000	0	-0.31	1	1
GIT1	0.027	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.042	-10000	0	-0.33	2	2

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.004	0.068	0.23	4	-0.32	5	9
BAG4	0.008	0.063	-10000	0	-0.31	18	18
BAD	0.011	0.059	0.22	24	-0.14	2	26
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	0.025	0.025	0.17	3	-0.31	2	5
BAX	0.007	0.043	0.16	20	-0.13	3	23
EnzymeConsortium:3.1.4.12	0.003	0.025	0.083	13	-0.085	5	18
IKBKB	0.013	0.078	0.26	14	-0.31	4	18
MAP2K2	0.001	0.063	0.23	18	-0.19	8	26
MAP2K1	0	0.061	0.21	20	-0.18	9	29
SMPD1	0.006	0.032	0.15	10	-0.096	1	11
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.014	0.078	0.3	8	-0.35	3	11
MAP2K4	0.005	0.042	0.18	13	-0.14	1	14
protein ubiquitination	0.01	0.082	0.28	10	-0.32	4	14
EnzymeConsortium:2.7.1.37	0	0.066	0.23	19	-0.2	7	26
response to UV	0	0.001	0.003	19	-0.002	6	25
RAF1	0.002	0.06	0.21	19	-0.19	9	28
CRADD	0.026	0.006	-10000	0	-10000	0	0
mol:ceramide	0.009	0.042	0.15	18	-0.13	4	22
I-kappa-B-alpha/RELA/p50/ubiquitin	0.034	0.009	-10000	0	-10000	0	0
MADD	0.026	0.006	-10000	0	-10000	0	0
MAP3K1	0.007	0.042	0.17	15	-0.14	2	17
TRADD	0.024	0.009	-10000	0	-10000	0	0
RELA/p50	0.026	0.006	-10000	0	-10000	0	0
MAPK3	0.003	0.062	0.22	19	-0.21	4	23
MAPK1	0.003	0.063	0.22	20	-0.2	5	25
p50/RELA/I-kappa-B-alpha	0.038	0.01	-10000	0	-10000	0	0
FADD	0.006	0.073	0.26	8	-0.32	5	13
KSR1	0.002	0.051	0.16	15	-0.16	14	29
MAPK8	0.002	0.052	0.2	14	-0.18	4	18
TRAF2	0.026	0.006	-10000	0	-10000	0	0
response to radiation	0	0.001	0.002	13	-0.002	1	14
CHUK	0.007	0.071	0.28	8	-0.32	3	11
TNF R/SODD	0.02	0.049	-10000	0	-0.21	18	18
TNF	0.013	0.077	0.17	12	-0.31	24	36
CYCS	0.023	0.061	0.17	43	-0.14	1	44
IKBKG	0.004	0.072	0.27	5	-0.3	5	10
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.007	0.066	0.27	1	-0.33	4	5
RELA	0.026	0.006	-10000	0	-10000	0	0
RIPK1	0.026	0.005	-10000	0	-10000	0	0
AIFM1	0.017	0.055	0.16	34	-0.14	1	35
TNF/TNF R/SODD	0.022	0.068	-10000	0	-0.18	41	41
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
response to heat	0	0.001	0.002	13	-0.002	1	14
CASP8	0.026	0.037	-10000	0	-0.45	2	2
NSMAF	0.016	0.08	0.21	32	-0.3	6	38
response to hydrogen peroxide	0	0.001	0.003	19	-0.002	6	25
BCL2	0.016	0.052	-10000	0	-0.31	12	12

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.007	0.072	-10000	0	-0.4	6	6
UGCG	-0.037	0.19	-10000	0	-0.63	44	44
AKT1/mTOR/p70S6K/Hsp90/TERT	0.046	0.1	0.31	10	-0.34	14	24
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.035	0.19	-10000	0	-0.62	44	44
mol:DAG	-0.006	0.11	-10000	0	-0.82	9	9
CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.12	0.29	5	-0.41	27	32
FRAP1	0.025	0.14	0.32	8	-0.46	28	36
FOXO3	0.026	0.1	0.34	8	-0.36	17	25
AKT1	0.028	0.11	0.28	6	-0.36	21	27
GAB2	0.026	0.006	-10000	0	-10000	0	0
SMPD1	0.018	0.041	-10000	0	-0.54	2	2
SGMS1	0.009	0.085	-10000	0	-0.59	9	9
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	-0.008	0.023	-10000	0	-0.2	6	6
CALM1	0.026	0.005	-10000	0	-10000	0	0
cell proliferation	0.016	0.14	0.28	14	-0.35	42	56
EIF3A	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.033	0.035	-10000	0	-0.24	6	6
RPS6KB1	0.017	0.087	-10000	0	-0.7	7	7
mol:sphingomyelin	-0.006	0.11	-10000	0	-0.82	9	9
natural killer cell activation	0	0.001	-10000	0	-0.01	1	1
JAK3	0.03	0.034	0.18	11	-0.31	3	14
PIK3R1	0.023	0.031	-10000	0	-0.31	4	4
JAK1	0.027	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MYC	0.066	0.13	0.38	24	-0.41	6	30
MYB	0.025	0.04	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.021	0.09	0.21	2	-0.32	19	21
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.045	0.086	-10000	0	-0.64	7	7
mol:PI-3-4-5-P3	0.022	0.089	0.21	2	-0.31	19	21
Rac1/GDP	0.015	0.024	-10000	0	-0.2	4	4
T cell proliferation	0.021	0.088	0.24	6	-0.3	19	25
SHC1	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.002	-10000	0	-10000	0	0
PRKCZ	0.02	0.089	0.23	4	-0.31	19	23
NF kappa B1 p50/RelA	0.035	0.12	-10000	0	-0.42	26	26
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.012	0.069	-10000	0	-0.35	13	13
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
IL2RA	0.046	0.065	0.17	76	-0.31	5	81
IL2RB	0.015	0.072	0.18	7	-0.31	22	29
TERT	0.07	0.069	0.17	149	-10000	0	149
E2F1	0.029	0.042	-10000	0	-0.38	3	3
SOS1	0.026	0.006	-10000	0	-10000	0	0
RPS6	0.027	0.01	0.17	2	-10000	0	2
mol:cAMP	-0.002	0.001	-10000	0	-10000	0	0
PTPN11	0.026	0.016	-10000	0	-0.31	1	1
IL2RG	0.029	0.043	0.18	15	-0.31	5	20
actin cytoskeleton organization	0.021	0.088	0.24	6	-0.3	19	25
GRB2	0.026	0.006	-10000	0	-10000	0	0
IL2	0.022	0.014	0.18	2	-10000	0	2
PIK3CA	0.025	0.027	-10000	0	-0.31	3	3
Rac1/GTP	0.039	0.034	-10000	0	-0.18	4	4
LCK	0.031	0.02	0.18	9	-10000	0	9
BCL2	0.008	0.19	0.34	4	-0.8	23	27

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.014	0.039	0.17	13	-10000	0	13
DAPP1	-0.042	0.14	0.27	6	-0.33	59	65
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.02	0.13	0.33	4	-0.4	22	26
mol:DAG	0.004	0.082	0.24	21	-0.19	13	34
HRAS	0.031	0.019	0.18	6	-10000	0	6
RAP1A	0.029	0.008	-10000	0	-10000	0	0
ARF5/GDP	0.025	0.072	0.23	7	-0.28	10	17
PLCG2	0.021	0.026	0.17	2	-0.31	2	4
PLCG1	0.026	0.005	-10000	0	-10000	0	0
ARF5	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.014	0.033	0.16	14	-10000	0	14
ARF1/GTP	-0.003	0.047	0.2	15	-10000	0	15
RHOA	0.026	0.005	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
RAP1A/GTP	-0.014	0.03	0.16	11	-10000	0	11
ADAP1	-0.014	0.042	0.18	15	-0.26	1	16
ARAP3	-0.014	0.033	0.15	14	-10000	0	14
INPPL1	0.026	0.005	-10000	0	-10000	0	0
PREX1	0.025	0.016	-10000	0	-0.31	1	1
ARHGEF6	0.026	0.015	-10000	0	-0.31	1	1
ARHGEF7	0.025	0.007	-10000	0	-10000	0	0
ARF1	0.026	0.006	-10000	0	-10000	0	0
NRAS	0.029	0.009	-10000	0	-10000	0	0
FYN	0.022	0.018	-10000	0	-0.31	1	1
ARF6	0.027	0.004	-10000	0	-10000	0	0
FGR	0.026	0.022	0.17	1	-0.31	2	3
mol:Ca2+	0.011	0.067	0.17	53	-0.12	5	58
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.023	0.03	-10000	0	-0.31	4	4
ZAP70	0.04	0.053	0.17	52	-0.31	3	55
mol:IP3	0.006	0.076	0.2	44	-0.16	7	51
LYN	0.023	0.01	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.074	0.23	7	-0.29	9	16
RhoA/GDP	0.022	0.046	0.21	7	-0.22	2	9
PDK1/Src/Hsp90	0.05	0.017	-10000	0	-10000	0	0
BLNK	0.024	0.017	-10000	0	-0.31	1	1
actin cytoskeleton reorganization	0.032	0.09	0.29	27	-0.27	4	31
SRC	0.026	0.006	-10000	0	-10000	0	0
PLEKHA2	-0.017	0.039	-10000	0	-0.24	13	13
RAC1	0.025	0.008	-10000	0	-10000	0	0
PTEN	0.021	0.015	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.018	0.034	0.16	10	-10000	0	10
RhoA/GTP	-0.017	0.029	0.17	8	-10000	0	8
Src family/SYK family/BLNK-LAT	-0.013	0.093	0.19	1	-0.27	33	34
BLK	0	0.1	0.17	32	-0.31	43	75
PDPK1	0.026	0.006	-10000	0	-10000	0	0
CYTH1	-0.014	0.035	0.14	19	-10000	0	19
HCK	0.024	0.031	0.17	1	-0.31	4	5
CYTH3	-0.014	0.036	0.16	14	-10000	0	14
CYTH2	-0.013	0.042	0.16	22	-10000	0	22
KRAS	0.028	0.011	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.035	0.13	-10000	0	-0.38	56	56
SGK1	-0.031	0.14	-10000	0	-0.42	54	54
INPP5D	0.01	0.074	-10000	0	-0.31	25	25
mol:GDP	0.015	0.075	0.22	9	-0.28	12	21
SOS1	0.026	0.005	-10000	0	-10000	0	0
SYK	0.023	0.035	0.17	1	-0.31	5	6
ARF6/GDP	-0.008	0.044	0.21	8	-0.22	2	10
mol:PI-3-4-5-P3	-0.012	0.041	0.16	20	-10000	0	20
ARAP3/RAP1A/GTP	-0.014	0.03	0.16	11	-10000	0	11
VAV1	0.012	0.068	0.17	1	-0.31	21	22
mol:PI-3-4-P2	-0.021	0.043	-10000	0	-0.21	23	23
RAS family/GTP/PI3K Class I	0.063	0.066	0.19	84	-0.15	1	85
PLEKHA1	-0.021	0.035	-10000	0	-0.18	22	22
Rac1/GDP	0.023	0.071	0.23	5	-0.28	10	15
LAT	0.029	0.032	0.17	13	-0.31	2	15
Rac1/GTP	0.016	0.062	0.18	1	-0.31	9	10
ITK	-0.018	0.044	0.15	20	-0.27	2	22
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.005	0.091	0.29	11	-0.26	15	26
LCK	0.03	0.02	0.17	9	-10000	0	9
BTK	-0.015	0.038	0.14	22	-10000	0	22

×

Signaling events mediated by PRL

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
CCNE1	0.028	0.015	0.17	5	-10000	0	5
mol:Halofuginone	0.003	0	-10000	0	-10000	0	0
ITGA1	0.004	0.081	-10000	0	-0.31	31	31
CDKN1A	0.009	0.047	-10000	0	-0.41	5	5
PRL-3/alpha Tubulin	0.046	0.042	0.14	66	-10000	0	66
mol:Ca2+	-0.037	0.053	0.21	4	-0.21	17	21
AGT	0.027	0.082	0.17	49	-0.31	20	69
CCNA2	-0.021	0.038	-10000	0	-10000	0	0
TUBA1B	0.027	0.003	-10000	0	-10000	0	0
EGR1	-0.006	0.058	0.26	1	-0.2	36	37
CDK2/Cyclin E1	0.042	0.057	0.26	1	-0.35	6	7
MAPK3	0.001	0.069	0.26	31	-10000	0	31
PRL-2 /Rab GGTase beta	0.038	0.009	-10000	0	-10000	0	0
MAPK1	0.001	0.07	0.26	32	-10000	0	32
PTP4A1	-0.017	0.036	-10000	0	-10000	0	0
PTP4A3	0.041	0.053	0.17	66	-10000	0	66
PTP4A2	0.027	0.003	-10000	0	-10000	0	0
ITGB1	0.003	0.072	0.26	34	-10000	0	34
SRC	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.02	0.053	-10000	0	-0.32	7	7
Rab GGTase beta/Rab GGTase alpha	0.039	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	0.009	0.052	-10000	0	-10000	0	0
RABGGTA	0.027	0.003	-10000	0	-10000	0	0
BCAR1	-0.027	0.035	-10000	0	-10000	0	0
RHOC	0.021	0.057	-10000	0	-0.31	8	8
RHOA	0.023	0.051	-10000	0	-0.32	5	5
cell motility	0.032	0.079	0.4	6	-0.3	6	12
PRL-1/alpha Tubulin	0.008	0.051	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.028	0.072	0.14	54	-0.22	26	80
ROCK1	0.031	0.069	0.35	3	-0.3	6	9
RABGGTB	0.026	0.005	-10000	0	-10000	0	0
CDK2	0.026	0.005	-10000	0	-10000	0	0
mitosis	-0.017	0.036	-10000	0	-10000	0	0
ATF5	0.028	0.015	0.17	5	-10000	0	5

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.012	0.003	-10000	0	-10000	0	0
SMARCC1	0.012	0.006	-10000	0	-10000	0	0
REL	-0.005	0.098	-10000	0	-0.31	46	46
HDAC7	-0.018	0.056	0.2	10	-0.23	13	23
JUN	0.024	0.031	0.17	1	-0.31	4	5
EP300	0.025	0.026	-10000	0	-0.31	3	3
KAT2B	0.026	0.005	-10000	0	-10000	0	0
KAT5	0.026	0.006	-10000	0	-10000	0	0
MAPK14	0.005	0.024	0.23	1	-0.21	3	4
FOXO1	0.022	0.011	-10000	0	-10000	0	0
T-DHT/AR	0.026	0.065	0.26	3	-0.23	14	17
MAP2K6	0.027	0.035	0.18	10	-0.31	3	13
BRM/BAF57	0.038	0.013	-10000	0	-10000	0	0
MAP2K4	0.025	0.01	-10000	0	-10000	0	0
SMARCA2	0.026	0.008	-10000	0	-10000	0	0
PDE9A	0.006	0.11	-10000	0	-0.49	21	21
NCOA2	-0.015	0.1	-10000	0	-0.31	53	53
CEBPA	0.027	0.003	-10000	0	-10000	0	0
EHMT2	0.027	0.006	-10000	0	-10000	0	0
cell proliferation	0.042	0.12	0.34	38	-0.28	4	42
NR0B1	0.023	0.018	0.17	6	-10000	0	6
EGR1	0.008	0.095	0.17	24	-0.31	36	60
RXRs/9cRA	0.007	0.083	-10000	0	-0.16	91	91
AR/RACK1/Src	0.009	0.064	0.19	23	-0.23	13	36
AR/GR	0.002	0.088	0.21	7	-0.24	42	49
GNB2L1	0.028	0.014	0.17	4	-10000	0	4
PKN1	0.029	0.019	0.17	8	-10000	0	8
RCHY1	0.027	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-0.026	1	1
MAPK8	0.002	0.036	-10000	0	-0.22	12	12
T-DHT/AR/TIF2/CARM1	-0.001	0.083	0.21	3	-0.24	38	41
SRC	-0.013	0.043	0.18	15	-0.16	13	28
NR3C1	0.019	0.05	-10000	0	-0.31	11	11
KLK3	0.008	0.14	-10000	0	-1.1	7	7
APPBP2	0.026	0.008	-10000	0	-10000	0	0
TRIM24	0.024	0.01	-10000	0	-10000	0	0
T-DHT/AR/TIP60	0.004	0.058	0.19	12	-0.23	15	27
TMPRSS2	-0.078	0.22	-10000	0	-0.51	96	96
RXRG	-0.042	0.14	0.17	6	-0.31	102	108
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.026	0.006	-10000	0	-10000	0	0
RXRB	0.027	0.003	-10000	0	-10000	0	0
CARM1	0.027	0.005	-10000	0	-10000	0	0
NR2C2	0.016	0.058	-10000	0	-0.31	15	15
KLK2	-0.012	0.08	0.22	1	-0.34	10	11
AR	-0.012	0.075	0.15	10	-0.25	39	49
SENP1	0.027	0.004	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
MDM2	0.026	0.007	-10000	0	-10000	0	0
SRY	0	0.004	0.031	7	-10000	0	7
GATA2	0.025	0.01	0.17	1	-10000	0	1
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.026	0.009	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	0.008	0.069	0.21	23	-0.23	14	37
positive regulation of transcription	0.025	0.01	0.17	1	-10000	0	1
DNAJA1	0.026	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.004	-10000	0	-10000	0	0
NCOA1	0.03	0.014	-10000	0	-10000	0	0
SPDEF	0.027	0.01	0.18	1	-10000	0	1
T-DHT/AR/TIF2	0.006	0.11	0.25	24	-0.25	40	64
T-DHT/AR/Hsp90	0.006	0.062	0.21	15	-0.23	15	30
GSK3B	0.026	0.007	-10000	0	-10000	0	0
NR2C1	0.026	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.016	0.029	0.18	1	-0.17	13	14
SIRT1	0.026	0.005	-10000	0	-10000	0	0
ZMIZ2	0.024	0.009	-10000	0	-10000	0	0
POU2F1	0.031	0.013	-10000	0	-0.11	1	1
T-DHT/AR/DAX-1	-0.005	0.063	0.2	15	-0.23	15	30
CREBBP	0.026	0.005	-10000	0	-10000	0	0
SMARCE1	0.026	0.008	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.01	0.041	-10000	0	-0.22	2	2
BIRC5	0.074	0.072	0.17	165	-0.31	1	166
NFKBIA	-0.004	0.038	0.25	7	-10000	0	7
CPEB1	-0.061	0.15	0.17	2	-0.31	129	131
AKT1	-0.004	0.034	0.23	6	-10000	0	6
NDEL1	0.024	0.008	-10000	0	-10000	0	0
Aurora A/BRCA1	0.007	0.031	-10000	0	-10000	0	0
NDEL1/TACC3	0.039	0.04	0.23	5	-0.13	1	6
GADD45A	0.025	0.022	-10000	0	-0.31	2	2
GSK3B	0.003	0.025	-10000	0	-10000	0	0
PAK1/Aurora A	0.008	0.042	-10000	0	-0.18	6	6
MDM2	0.026	0.006	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.018	0.045	0.26	10	-10000	0	10
TP53	-0.008	0.066	-10000	0	-0.21	47	47
DLG7	-0.003	0.022	0.13	5	-0.13	2	7
AURKAIP1	0.029	0.02	0.17	9	-10000	0	9
ARHGEF7	0.025	0.007	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.041	0.042	0.24	5	-0.14	1	6
G2/M transition of mitotic cell cycle	0.007	0.031	-10000	0	-10000	0	0
AURKA	0.001	0.029	0.16	5	-0.16	2	7
AURKB	0.028	0.049	0.11	19	-0.11	31	50
CDC25B	0.005	0.027	0.29	1	-0.25	2	3
G2/M transition checkpoint	-0.003	0.02	-10000	0	-10000	0	0
mRNA polyadenylation	-0.034	0.077	-10000	0	-0.16	117	117
Aurora A/CPEB	-0.034	0.078	-10000	0	-0.16	117	117
Aurora A/TACC1/TRAP/chTOG	0.038	0.039	-10000	0	-0.16	4	4
BRCA1	0.026	0.009	0.17	1	-10000	0	1
centrosome duplication	0.008	0.042	-10000	0	-0.18	6	6
regulation of centrosome cycle	0.037	0.038	0.22	5	-0.13	1	6
spindle assembly	0.036	0.038	-10000	0	-0.16	4	4
TDRD7	0.026	0.006	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.065	0.059	0.22	7	-0.18	2	9
CENPA	0.043	0.042	0.18	9	-0.22	1	10
Aurora A/PP2A	0.011	0.038	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.004	0.028	0.23	4	-10000	0	4
negative regulation of DNA binding	-0.01	0.068	-10000	0	-0.2	53	53
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.037	0.011	-10000	0	-10000	0	0
RASA1	0.025	0.016	-10000	0	-0.31	1	1
Ajuba/Aurora A	-0.003	0.02	-10000	0	-10000	0	0
mitotic prometaphase	-0.002	0.028	0.082	3	-10000	0	3
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.029	0.16	5	-0.16	2	7
TACC1	0.017	0.035	-10000	0	-0.31	5	5
TACC3	0.037	0.038	0.17	35	-10000	0	35
Aurora A/Antizyme1	0.039	0.032	-10000	0	-10000	0	0
Aurora A/RasGAP	0.011	0.038	-10000	0	-0.19	1	1
OAZ1	0.027	0.004	-10000	0	-10000	0	0
RAN	0.026	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.002	0.026	-10000	0	-10000	0	0
GIT1	0.027	0.002	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.046	0.031	-10000	0	-0.18	6	6
Importin alpha/Importin beta/TPX2	-0.018	0.045	0.26	10	-10000	0	10
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	-0.004	0.049	0.22	9	-0.15	1	10
PAK1	0.022	0.037	-10000	0	-0.31	6	6
CKAP5	0.026	0.005	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.015	0.17	0.41	1	-0.64	10	11
PCK1	-0.006	0.15	-10000	0	-0.64	8	8
HNF4A	-0.025	0.22	0.54	1	-0.79	19	20
KCNJ11	-0.006	0.19	-10000	0	-0.71	6	6
AKT1	0.036	0.11	0.34	1	-0.33	1	2
response to starvation	-0.001	0.021	-10000	0	-0.13	9	9
DLK1	-0.034	0.25	0.61	3	-0.76	32	35
NKX2-1	-0.001	0.11	0.27	4	-0.33	6	10
ACADM	-0.021	0.18	-10000	0	-0.64	12	12
TAT	-0.024	0.17	-10000	0	-0.6	20	20
CEBPB	0.026	0.017	-10000	0	-10000	0	0
CEBPA	0.028	0.016	-10000	0	-10000	0	0
TTR	-0.011	0.25	0.42	2	-1.1	19	21
PKLR	-0.01	0.19	0.39	2	-0.64	11	13
APOA1	-0.056	0.3	-10000	0	-1.1	22	22
CPT1C	-0.022	0.2	0.47	1	-0.74	14	15
ALAS1	0.005	0.12	-10000	0	-0.57	1	1
TFRC	-0.01	0.19	-10000	0	-0.66	15	15
FOXF1	0.006	0.07	-10000	0	-0.31	23	23
NF1	0.03	0.003	-10000	0	-10000	0	0
HNF1A (dimer)	0.044	0.049	0.18	51	-0.16	2	53
CPT1A	-0.01	0.18	0.39	3	-0.64	10	13
HMGCS1	-0.013	0.18	-10000	0	-0.64	10	10
NR3C1	0.024	0.051	-10000	0	-0.3	11	11
CPT1B	-0.015	0.18	-10000	0	-0.63	11	11
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.028	0.014	-10000	0	-0.16	2	2
GCK	-0.024	0.23	0.44	2	-0.73	28	30
CREB1	0.032	0.012	-10000	0	-0.18	1	1
IGFBP1	0.001	0.11	-10000	0	-0.61	2	2
PDX1	0.01	0.15	0.51	1	-1.3	2	3
UCP2	-0.014	0.19	-10000	0	-0.66	12	12
ALDOB	0.003	0.2	0.47	6	-0.66	8	14
AFP	0.01	0.066	-10000	0	-10000	0	0
BDH1	-0.012	0.18	0.42	1	-0.63	11	12
HADH	-0.007	0.19	-10000	0	-0.68	7	7
F2	-0.036	0.23	0.51	1	-0.86	10	11
HNF1A	0.044	0.049	0.18	51	-0.16	2	53
G6PC	0.015	0.071	0.4	1	-10000	0	1
SLC2A2	0.015	0.13	0.43	2	-0.51	3	5
INS	-0.016	0.031	0.17	11	-10000	0	11
FOXA1	0.044	0.036	0.27	1	-0.25	2	3
FOXA3	0.023	0.12	0.22	7	-0.3	53	60
FOXA2	0.006	0.23	0.47	2	-0.68	14	16
ABCC8	-0.056	0.29	-10000	0	-0.75	58	58
ALB	0.015	0.086	-10000	0	-0.81	2	2

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.012	0.07	0.17	1	-0.31	22	23
HRAS	0.028	0.017	0.17	6	-10000	0	6
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
AKT	0.03	0.098	0.24	29	-0.25	21	50
FOXO3	0.023	0.01	-10000	0	-10000	0	0
AKT1	0.026	0.005	-10000	0	-10000	0	0
FOXO1	0.022	0.011	-10000	0	-10000	0	0
AKT3	0.025	0.016	-10000	0	-0.31	1	1
FOXO4	0.026	0.015	-10000	0	-0.31	1	1
MET	-0.004	0.093	-10000	0	-0.31	42	42
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
PIK3CB	0.025	0.007	-10000	0	-10000	0	0
NRAS	0.026	0.016	-10000	0	-0.31	1	1
PIK3CG	0.003	0.086	0.17	5	-0.31	34	39
PIK3R3	0.027	0.004	-10000	0	-10000	0	0
PIK3R2	0.027	0.002	-10000	0	-10000	0	0
NF1	0.027	0.003	-10000	0	-10000	0	0
RAS	-0.004	0.065	0.18	1	-0.16	56	57
ERBB2	0.025	0.026	-10000	0	-0.31	3	3
proliferation/survival/translation	-0.013	0.092	0.25	34	-0.2	5	39
PI3K	0.012	0.095	0.22	28	-0.22	38	66
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
KRAS	0.025	0.007	-10000	0	-10000	0	0
FOXO	0.048	0.054	0.22	13	-10000	0	13
AKT2	0.027	0.004	-10000	0	-10000	0	0
PTEN	0.021	0.011	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.011	0.043	-10000	0	-0.27	10	10
FRAP1	0.024	0.055	0.23	3	-0.34	3	6
AKT1	0.013	0.068	0.15	74	-0.24	10	84
INSR	0.027	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.032	0.018	0.13	12	-0.092	1	13
mol:GTP	0.045	0.069	0.24	14	-0.24	7	21
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.007	0.024	-10000	0	-0.16	3	3
TSC2	0.026	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.012	0.033	-10000	0	-0.21	7	7
TSC1	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.016	0.054	-10000	0	-0.26	17	17
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.023	0.037	-10000	0	-0.18	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.026	0.005	-10000	0	-10000	0	0
RPS6KB1	0.033	0.069	0.23	16	-0.26	3	19
MAP3K5	0.002	0.032	0.18	4	-0.19	10	14
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
apoptosis	0.002	0.032	0.18	4	-0.19	10	14
mol:LY294002	0	0	-10000	0	-0.001	17	17
EIF4B	0.033	0.073	0.24	22	-0.24	3	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.049	0.061	0.23	11	-0.23	3	14
eIF4E/eIF4G1/eIF4A1	0.016	0.029	-10000	0	-0.25	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.028	0.061	-10000	0	-0.26	17	17
mTOR/RHEB/GTP/Raptor/GBL	0.03	0.062	0.2	32	-0.14	3	35
FKBP1A	0.027	0.004	-10000	0	-10000	0	0
RHEB/GTP	0.044	0.06	0.24	9	-0.21	7	16
mol:Amino Acids	0	0	-10000	0	-0.001	17	17
FKBP12/Rapamycin	0.021	0.004	-10000	0	-10000	0	0
PDPK1	-0.011	0.046	0.15	10	-0.28	8	18
EIF4E	0.027	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.031	0.1	-10000	0	-0.52	12	12
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.011	0.038	-10000	0	-10000	0	0
TSC1/TSC2	0.05	0.074	0.25	14	-0.25	7	21
tumor necrosis factor receptor activity	0	0	0.001	17	-10000	0	17
RPS6	0.027	0.01	0.17	2	-10000	0	2
PPP5C	0.027	0.003	-10000	0	-10000	0	0
EIF4G1	0.026	0.006	-10000	0	-10000	0	0
IRS1	-0.001	0.055	-10000	0	-0.28	18	18
INS	0.022	0.024	0.17	12	-10000	0	12
PTEN	0.021	0.011	-10000	0	-10000	0	0
PDK2	-0.01	0.047	0.16	11	-0.28	8	19
EIF4EBP1	-0.14	0.4	-10000	0	-1	79	79
PIK3CA	0.024	0.027	-10000	0	-0.31	3	3
PPP2R5D	0.024	0.058	0.24	9	-0.32	3	12
peptide biosynthetic process	-0.012	0.03	0.18	11	-10000	0	11
RHEB	0.025	0.008	-10000	0	-10000	0	0
EIF4A1	0.023	0.01	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	39	-0.002	1	40
EEF2	-0.012	0.03	0.18	11	-10000	0	11
eIF4E/4E-BP1	-0.12	0.38	-10000	0	-0.97	79	79

×

Retinoic acid receptors-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.003	-10000	0	-10000	0	0
HDAC3	0.026	0.005	-10000	0	-10000	0	0
VDR	0.024	0.035	0.17	2	-0.31	5	7
Cbp/p300/PCAF	0.049	0.024	-10000	0	-0.18	3	3
EP300	0.025	0.026	-10000	0	-0.31	3	3
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.013	0.048	0.17	2	-0.23	8	10
KAT2B	0.026	0.005	-10000	0	-10000	0	0
MAPK14	0.027	0.004	-10000	0	-10000	0	0
AKT1	0.014	0.068	0.19	29	-0.21	13	42
RAR alpha/9cRA/Cyclin H	0.032	0.077	0.21	4	-0.26	18	22
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.014	0.05	0.2	1	-0.22	8	9
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.012	0.07	-10000	0	-0.27	21	21
NCOR2	0.026	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.024	0.12	2	-0.21	5	7
RXRs/RARs/NRIP1/9cRA	0.002	0.11	0.36	4	-0.43	18	22
NCOA2	-0.015	0.1	-10000	0	-0.31	53	53
NCOA3	0.026	0.006	-10000	0	-10000	0	0
NCOA1	0.027	0.004	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.035	0.17	2	-0.31	5	7
RARG	0.021	0.045	-10000	0	-0.31	9	9
RAR gamma1/9cRA	0.032	0.029	-10000	0	-0.18	9	9
MAPK3	0.027	0.005	-10000	0	-10000	0	0
MAPK1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	0.019	0.052	-10000	0	-0.31	12	12
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.007	0.1	-10000	0	-0.41	21	21
RARA	0.002	0.056	-10000	0	-0.21	29	29
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.007	0.073	-10000	0	-0.26	21	21
PRKCA	0.013	0.069	-10000	0	-0.31	22	22
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.001	0.11	0.38	1	-0.42	21	22
RXRG	-0.042	0.12	0.2	1	-0.26	108	109
RXRA	0.005	0.056	-10000	0	-0.19	28	28
RXRB	0.009	0.054	0.2	1	-0.24	21	22
VDR/Vit D3/DNA	0.018	0.024	0.12	2	-0.21	5	7
RBP1	0.002	0.088	0.17	3	-0.31	36	39
CRBP1/9-cic-RA	0.003	0.06	0.12	3	-0.21	36	39
RARB	0.024	0.031	-10000	0	-0.31	4	4
PRKCG	0.028	0.025	0.18	13	-10000	0	13
MNAT1	0.026	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	0.004	0.11	0.24	1	-0.45	18	19
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.006	0.097	0.3	5	-0.37	19	24
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.074	0.24	11	-0.26	13	24
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.001	0.11	0.43	1	-0.42	21	22
positive regulation of DNA binding	0.021	0.068	-10000	0	-0.25	18	18
NRIP1	-0.001	0.1	-10000	0	-0.48	8	8
RXRs/RARs	-0.004	0.11	0.3	2	-0.42	22	24
RXRs/RXRs/DNA/9cRA	-0.008	0.095	-10000	0	-0.41	21	21
PRKACA	0.027	0.003	-10000	0	-10000	0	0
CDK7	0.025	0.008	-10000	0	-10000	0	0
TFIIH	0.048	0.021	-10000	0	-10000	0	0
RAR alpha/9cRA	0.041	0.062	-10000	0	-0.28	6	6
CCNH	0.027	0.015	0.17	4	-10000	0	4
CREBBP	0.026	0.005	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.042	0.032	-10000	0	-0.15	7	7

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.026	0.006	-10000	0	-10000	0	0
ELF1	0.027	0.048	-10000	0	-0.3	8	8
CCNA2	0.048	0.053	0.17	74	-10000	0	74
PIK3CA	0.024	0.027	-10000	0	-0.31	3	3
JAK3	0.029	0.034	0.17	11	-0.31	3	14
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
JAK1	0.026	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.018	0.081	0.19	1	-0.34	12	13
SHC1	0.026	0.006	-10000	0	-10000	0	0
SP1	0.014	0.072	-10000	0	-0.28	27	27
IL2RA	0.015	0.065	0.31	1	-0.4	8	9
IL2RB	0.014	0.072	0.17	7	-0.31	22	29
SOS1	0.026	0.005	-10000	0	-10000	0	0
IL2RG	0.028	0.042	0.17	15	-0.31	5	20
G1/S transition of mitotic cell cycle	-0.013	0.2	0.37	10	-0.69	30	40
PTPN11	0.026	0.016	-10000	0	-0.31	1	1
CCND2	-0.014	0.13	-10000	0	-0.58	23	23
LCK	0.03	0.02	0.17	9	-10000	0	9
GRB2	0.026	0.005	-10000	0	-10000	0	0
IL2	0.022	0.012	0.17	2	-10000	0	2
CDK6	0.016	0.054	-10000	0	-0.31	13	13
CCND3	0.021	0.084	0.37	5	-0.36	6	11

×

LPA4-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.01	0.013	-10000	0	-0.18	3	3
ADCY5	-0.03	0.055	-10000	0	-0.18	61	61
ADCY6	-0.009	0.002	-10000	0	-10000	0	0
ADCY7	-0.009	0.004	-10000	0	-10000	0	0
ADCY1	-0.01	0.031	0.22	6	-0.18	3	9
ADCY2	-0.014	0.028	-10000	0	-0.18	14	14
ADCY3	-0.009	0.002	-10000	0	-10000	0	0
ADCY8	-0.009	0.006	-10000	0	-10000	0	0
PRKCE	-0.006	0.001	-10000	0	-10000	0	0
ADCY9	-0.01	0.011	-10000	0	-0.18	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.021	0.093	0.24	47	-0.16	3	50

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.064	0.037	0.2	3	-0.27	1	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.026	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.052	0.053	0.29	15	-0.25	1	16
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.053	0.025	-10000	0	-0.22	1	1
antigen processing and presentation of peptide antigen via MHC class I	0.002	0.05	-10000	0	-0.21	12	12
CaM/Ca2+	0.063	0.037	-10000	0	-0.26	1	1
RAP1A	0.026	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.023	0.031	0.16	9	-0.26	1	10
AKT1	0.001	0.075	0.22	36	-0.47	1	37
MAP2K1	-0.009	0.049	0.22	17	-0.38	1	18
MAP3K11	-0.007	0.052	0.24	18	-0.26	1	19
IFNGR1	0.028	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.017	0.13	-10000	0	-0.3	72	72
Rap1/GTP	-0.023	0.018	-10000	0	-0.32	1	1
CRKL/C3G	0.037	0.011	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.073	0.041	0.26	1	-0.2	1	2
CEBPB	0.025	0.07	0.3	13	-0.42	1	14
STAT3	0.026	0.005	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.072	0.072	-10000	0	-0.88	2	2
STAT1	-0.005	0.057	0.23	23	-0.26	1	24
CALM1	0.026	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.027	0.045	0.18	31	-10000	0	31
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
STAT1 (dimer)/PIAS1	0.029	0.057	0.25	21	-0.26	1	22
CEBPB/PTGES2/Cbp/p300	0.031	0.038	-10000	0	-0.28	1	1
mol:Ca2+	0.061	0.036	0.19	3	-0.27	1	4
MAPK3	0.011	0.069	-10000	0	-0.51	4	4
STAT1 (dimer)	0.009	0.07	-10000	0	-0.28	11	11
MAPK1	0.005	0.097	-10000	0	-0.63	8	8
JAK2	0.027	0.018	-10000	0	-0.33	1	1
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
JAK1	0.028	0.009	-10000	0	-10000	0	0
CAMK2D	0.026	0.005	-10000	0	-10000	0	0
DAPK1	0.026	0.07	0.27	19	-0.37	2	21
SMAD7	0.009	0.051	0.18	19	-0.12	6	25
CBL/CRKL/C3G	0.035	0.046	0.27	10	-0.37	1	11
PI3K	0.051	0.048	-10000	0	-0.21	6	6
IFNG	0.027	0.045	0.18	31	-10000	0	31
apoptosis	0.026	0.067	0.26	15	-0.35	3	18
CAMK2G	0.026	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.026	0.005	-10000	0	-10000	0	0
CAMK2A	-0.022	0.13	0.17	14	-0.31	77	91
CAMK2B	0.031	0.041	0.17	26	-0.31	2	28
FRAP1	0	0.071	0.2	38	-0.44	1	39
PRKCD	-0.001	0.072	0.21	34	-0.48	1	35
RAP1B	0.026	0.006	-10000	0	-10000	0	0
negative regulation of cell growth	0.002	0.05	-10000	0	-0.21	12	12
PTPN2	0.026	0.006	-10000	0	-10000	0	0
EP300	0.025	0.026	-10000	0	-0.31	3	3
IRF1	-0.001	0.059	0.25	15	-0.31	1	16
STAT1 (dimer)/PIASy	0.02	0.058	0.24	23	-0.26	1	24
SOCS1	0.02	0.075	-10000	0	-1.1	2	2
mol:GDP	0.032	0.043	0.26	9	-0.36	1	10
CASP1	0.005	0.061	0.19	19	-0.2	15	34
PTGES2	0.025	0.007	-10000	0	-10000	0	0
IRF9	0.023	0.037	0.16	18	-10000	0	18
mol:PI-3-4-5-P3	0.037	0.04	-10000	0	-0.2	6	6
RAP1/GDP	0.03	0.029	-10000	0	-0.33	1	1
CBL	-0.008	0.052	0.24	17	-0.39	1	18
MAP3K1	-0.008	0.048	0.22	16	-0.39	1	17
PIAS1	0.026	0.015	-10000	0	-0.31	1	1
PIAS4	0.026	0.004	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	0.002	0.05	-10000	0	-0.21	12	12
PTPN11	-0.01	0.03	0.16	10	-0.27	1	11
CREBBP	0.026	0.005	-10000	0	-10000	0	0
RAPGEF1	0.026	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.025	0.026	-10000	0	-0.31	3	3
HDAC4	0.027	0.004	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.021	-10000	0	-0.15	6	6
CDKN1A	-0.009	0.005	-10000	0	-10000	0	0
KAT2B	0.026	0.005	-10000	0	-10000	0	0
BAX	0.027	0.01	0.17	2	-10000	0	2
FOXO3	-0.002	0.024	0.3	3	-10000	0	3
FOXO1	0.022	0.011	-10000	0	-10000	0	0
FOXO4	0.011	0.02	-10000	0	-0.21	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
TAT	0.028	0.035	0.17	25	-10000	0	25
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.017	0.023	0.26	1	-0.21	4	5
PPARGC1A	-0.068	0.15	-10000	0	-0.31	139	139
FHL2	0.013	0.066	-10000	0	-0.31	20	20
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.037	0.013	-10000	0	-10000	0	0
HIST2H4A	-0.012	0.021	0.15	6	-10000	0	6
SIRT1/FOXO3a	0.014	0.027	0.23	3	-0.19	1	4
SIRT1	0.024	0.012	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.049	0.017	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.03	0.037	0.21	1	-0.18	6	7
apoptosis	-0.05	0.016	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.025	0.093	-10000	0	-0.17	135	135
p53/SIRT1	0.027	0.016	-10000	0	-10000	0	0
SIRT1/FOXO4	0.027	0.029	-10000	0	-0.18	4	4
FOXO1/FHL2/SIRT1	0.033	0.043	-10000	0	-0.15	20	20
HIST1H1E	0.018	0.034	0.15	9	-0.21	6	15
SIRT1/p300	0.035	0.023	-10000	0	-0.22	3	3
muscle cell differentiation	-0.027	0.03	0.18	4	-0.21	4	8
TP53	0.02	0.011	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.05	0.016	-10000	0	-10000	0	0
CREBBP	0.026	0.005	-10000	0	-10000	0	0
MEF2D	0.026	0.005	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.035	0.029	0.14	24	-10000	0	24
ACSS2	-0.012	0.01	0.1	3	-10000	0	3
SIRT1/PCAF/MYOD	0.027	0.03	0.22	4	-0.18	4	8

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.026	0.005	-10000	0	-10000	0	0
NFATC1	0.017	0.083	0.28	10	-0.39	3	13
NFATC2	-0.002	0.066	0.18	10	-0.2	20	30
NFATC3	0.017	0.008	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.031	0.11	0.2	4	-0.3	50	54
Exportin 1/Ran/NUP214	0.049	0.017	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.01	0.12	0.21	1	-0.3	50	51
BCL2/BAX	0.029	0.042	0.14	2	-0.21	12	14
CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.007	-10000	0	-10000	0	0
BAX	0.027	0.01	0.17	2	-10000	0	2
MAPK14	0.027	0.004	-10000	0	-10000	0	0
BAD	0.027	0.008	0.17	1	-10000	0	1
CABIN1/MEF2D	-0.018	0.11	0.27	3	-0.29	50	53
Calcineurin A alpha-beta B1/BCL2	0.016	0.052	-10000	0	-0.31	12	12
FKBP8	0.027	0.002	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.017	0.11	0.29	50	-0.27	3	53
KPNB1	0.026	0.005	-10000	0	-10000	0	0
KPNA2	0.028	0.015	0.17	5	-10000	0	5
XPO1	0.027	0.004	-10000	0	-10000	0	0
SFN	-0.006	0.1	-10000	0	-0.31	49	49
MAP3K8	0.018	0.054	0.17	1	-0.31	13	14
NFAT4/CK1 alpha	0.023	0.02	-10000	0	-0.15	1	1
MEF2D/NFAT1/Cbp/p300	0.029	0.087	0.22	4	-0.23	21	25
CABIN1	-0.031	0.11	0.2	4	-0.3	49	53
CALM1	0.026	0.006	-10000	0	-10000	0	0
RAN	0.026	0.006	-10000	0	-10000	0	0
MAP3K1	0.023	0.017	-10000	0	-0.31	1	1
CAMK4	0.006	0.078	0.17	1	-0.31	28	29
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.026	0.005	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.039	0.021	-10000	0	-0.21	2	2
YWHAB	0.026	0.005	-10000	0	-10000	0	0
MAPK8	0.018	0.052	-10000	0	-0.31	12	12
MAPK9	0.026	0.005	-10000	0	-10000	0	0
YWHAG	0.025	0.008	-10000	0	-10000	0	0
FKBP1A	0.027	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.016	0.079	0.28	5	-0.33	5	10
PRKCH	0.026	0.004	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.036	0.024	-10000	0	-0.21	3	3
CASP3	0.027	0.004	-10000	0	-10000	0	0
PIM1	0.028	0.021	0.17	5	-0.31	1	6
Calcineurin A alpha-beta B1/FKBP12/FK506	0.018	0.005	-10000	0	-10000	0	0
apoptosis	0.015	0.018	-10000	0	-0.22	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.049	-10000	0	-0.24	5	5
PRKCB	-0.047	0.14	-10000	0	-0.31	107	107
PRKCE	0.026	0.005	-10000	0	-10000	0	0
JNK2/NFAT4	0.016	0.053	-10000	0	-0.14	4	4
BAD/BCL-XL	0.038	0.011	0.14	1	-10000	0	1
PRKCD	0.026	0.005	-10000	0	-10000	0	0
NUP214	0.026	0.006	-10000	0	-10000	0	0
PRKCZ	0.026	0.005	-10000	0	-10000	0	0
PRKCA	0.011	0.069	-10000	0	-0.31	22	22
PRKCG	0.027	0.025	0.17	13	-10000	0	13
PRKCQ	0.008	0.085	0.17	10	-0.31	31	41
FKBP38/BCL2	0.029	0.041	-10000	0	-0.21	12	12
EP300	0.024	0.027	-10000	0	-0.31	3	3
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.027	0.004	-10000	0	-10000	0	0
NFATc/JNK1	0.028	0.082	0.28	10	-0.37	3	13
CaM/Ca2+/FKBP38	0.035	0.011	-10000	0	-10000	0	0
FKBP12/FK506	0.02	0.003	-10000	0	-10000	0	0
CSNK1A1	0.011	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.021	0.049	0.13	1	-0.17	27	28
NFATc/ERK1	0.028	0.081	0.28	9	-0.37	3	12
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.01	0.12	-10000	0	-0.29	50	50
NR4A1	0.004	0.086	0.19	15	-0.34	14	29
GSK3B	0.025	0.007	-10000	0	-10000	0	0
positive T cell selection	0.017	0.008	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.002	0.049	0.15	2	-0.17	13	15
RCH1/ KPNB1	0.04	0.014	0.14	5	-10000	0	5
YWHAQ	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.027	0.004	-10000	0	-10000	0	0
AKAP5	0.027	0.028	0.17	7	-0.31	2	9
MEF2D	0.025	0.009	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.021	0.011	-10000	0	-10000	0	0
NFATc/p38 alpha	0.028	0.08	0.27	7	-0.37	3	10
CREBBP	0.025	0.009	-10000	0	-10000	0	0
BCL2	0.016	0.052	-10000	0	-0.31	12	12

×

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

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
BAG4	0.008	0.063	-10000	0	-0.31	18	18
Caspase 8 (4 units)	0.029	0.06	-10000	0	-0.27	4	4
NEF	0	0.02	-10000	0	-0.13	10	10
NFKBIA	0.027	0.009	-10000	0	-10000	0	0
BIRC3	0.017	0.037	0.18	13	-0.37	2	15
CYCS	0.01	0.063	0.18	34	-0.22	15	49
RIPK1	0.026	0.005	-10000	0	-10000	0	0
CD247	0.026	0.054	0.18	17	-0.21	15	32
MAP2K7	0.013	0.1	0.28	1	-0.58	9	10
protein ubiquitination	0.014	0.085	0.3	20	-0.3	4	24
CRADD	0.026	0.006	-10000	0	-10000	0	0
DAXX	0.027	0.003	-10000	0	-10000	0	0
FAS	0.02	0.037	-10000	0	-0.31	6	6
BID	0.006	0.049	0.18	5	-0.23	14	19
NF-kappa-B/RelA/I kappa B alpha	0.055	0.025	-10000	0	-0.21	2	2
TRADD	0.024	0.009	-10000	0	-10000	0	0
MAP3K5	0.026	0.017	0.17	1	-0.31	1	2
CFLAR	0.027	0.003	-10000	0	-10000	0	0
FADD	0.026	0.006	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.055	0.026	-10000	0	-0.21	2	2
MAPK8	0.011	0.1	0.34	4	-0.58	8	12
APAF1	0.026	0.006	-10000	0	-10000	0	0
TRAF1	0.026	0.009	0.17	1	-10000	0	1
TRAF2	0.026	0.006	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.012	0.053	0.19	5	-0.24	15	20
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.008	0.067	-10000	0	-0.33	7	7
CHUK	0.01	0.076	0.29	14	-0.32	4	18
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.063	0.041	-10000	0	-0.19	5	5
TCRz/NEF	0.021	0.054	0.15	17	-0.24	15	32
TNF	0.014	0.076	0.17	12	-0.31	24	36
FASLG	0.004	0.072	-10000	0	-0.38	15	15
NFKB1	0.027	0.013	-10000	0	-0.16	1	1
TNFR1A/BAG4/TNF-alpha	0.022	0.068	-10000	0	-0.18	41	41
CASP6	0.033	0.064	-10000	0	-0.45	4	4
CASP7	0.019	0.088	0.33	14	-0.55	2	16
RELA	0.026	0.01	-10000	0	-10000	0	0
CASP2	0.021	0.034	-10000	0	-0.31	5	5
CASP3	0.021	0.08	0.32	12	-0.55	2	14
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
TNFR1A/BAG4	0.02	0.049	-10000	0	-0.21	18	18
CASP8	0.027	0.002	-10000	0	-10000	0	0
CASP9	0.027	0.003	-10000	0	-10000	0	0
MAP3K14	0.006	0.066	0.24	3	-0.31	7	10
APAF-1/Caspase 9	0.016	0.059	-10000	0	-0.32	4	4
BCL2	0.007	0.098	0.34	6	-0.52	8	14

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.024	0.049	0.2	4	-0.29	3	7
PDGFB-D/PDGFRB/SLAP	0.034	0.027	0.16	11	-10000	0	11
PDGFB-D/PDGFRB/APS/CBL	0.049	0.03	-10000	0	-0.18	2	2
AKT1	0.014	0.096	0.27	39	-0.26	1	40
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.03	0.064	0.27	7	-0.32	4	11
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
FGR	0.014	0.048	-10000	0	-0.4	4	4
mol:Ca2+	0.016	0.066	0.26	7	-0.38	4	11
MYC	0.069	0.13	0.4	43	-0.29	1	44
SHC1	0.026	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.031	0.032	0.16	20	-0.15	1	21
LRP1/PDGFRB/PDGFB	0.053	0.018	-10000	0	-0.18	1	1
GRB10	0.025	0.008	-10000	0	-10000	0	0
PTPN11	0.025	0.016	-10000	0	-0.31	1	1
GO:0007205	0.016	0.066	0.25	7	-0.38	4	11
PTEN	0.021	0.011	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
GRB7	0.027	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.038	0.017	0.14	2	-0.22	1	3
PDGFB-D/PDGFRB/GRB10	0.037	0.015	0.14	2	-10000	0	2
cell cycle arrest	0.034	0.027	0.16	11	-10000	0	11
HRAS	0.028	0.017	0.17	6	-10000	0	6
HIF1A	0.006	0.089	0.24	42	-0.25	2	44
GAB1	0.017	0.074	0.27	8	-0.29	9	17
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.017	0.069	0.26	14	-0.28	3	17
PDGFB-D/PDGFRB	0.051	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.04	0.01	0.14	2	-10000	0	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.033	0.037	0.2	1	-10000	0	1
positive regulation of MAPKKK cascade	0.038	0.017	0.14	2	-0.22	1	3
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
mol:IP3	0.016	0.067	0.26	7	-0.39	4	11
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.026	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.04	0.011	0.14	2	-10000	0	2
SHB	0.024	0.026	-10000	0	-0.31	3	3
BLK	-0.1	0.2	0.33	2	-0.4	142	144
PTPN2	0.027	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.039	0.012	0.14	2	-10000	0	2
BCAR1	0.022	0.011	-10000	0	-10000	0	0
VAV2	0.024	0.081	0.28	13	-0.3	8	21
CBL	0.025	0.016	-10000	0	-0.31	1	1
PDGFB-D/PDGFRB/DEP1	0.039	0.012	0.14	2	-10000	0	2
LCK	0.017	0.035	0.21	1	-0.36	1	2
PDGFRB	0.028	0.011	0.18	2	-10000	0	2
ACP1	0.027	0.004	-10000	0	-10000	0	0
HCK	0.014	0.059	-10000	0	-0.45	6	6
ABL1	0.007	0.076	0.24	9	-0.26	13	22
PDGFB-D/PDGFRB/CBL	0.012	0.078	0.35	3	-0.33	10	13
PTPN1	0.027	0.006	-10000	0	-10000	0	0
SNX15	0.026	0.006	-10000	0	-10000	0	0
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT1	0.029	0.019	0.17	8	-10000	0	8
cell proliferation	0.068	0.13	0.38	46	-0.27	1	47
SLA	0.025	0.025	0.17	11	-10000	0	11
actin cytoskeleton reorganization	0.01	0.071	0.2	48	-10000	0	48
SRC	0.009	0.068	0.36	1	-0.45	8	9
PI3K	-0.02	0.022	-10000	0	-0.18	5	5
PDGFB-D/PDGFRB/GRB7/SHC	0.051	0.017	-10000	0	-10000	0	0
SH2B2	0.028	0.03	0.17	14	-0.31	1	15
PLCgamma1/SPHK1	0.03	0.065	0.27	7	-0.33	4	11
LYN	0.007	0.055	-10000	0	-0.39	7	7
LRP1	0.026	0.017	0.17	1	-0.31	1	2
SOS1	0.026	0.005	-10000	0	-10000	0	0
STAT5B	0.026	0.005	-10000	0	-10000	0	0
STAT5A	0.026	0.005	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.061	0.039	-10000	0	-10000	0	0
SPHK1	0.031	0.025	0.18	14	-10000	0	14
EDG1	0.001	0.002	-10000	0	-10000	0	0
mol:DAG	0.016	0.067	0.26	7	-0.39	4	11
PLCG1	0.016	0.067	0.27	6	-0.4	4	10
NHERF/PDGFRB	0.052	0.02	-10000	0	-10000	0	0
YES1	-0.007	0.12	0.21	1	-0.5	24	25
cell migration	0.051	0.02	-10000	0	-10000	0	0
SHC/Grb2/SOS1	0.07	0.033	-10000	0	-10000	0	0
SLC9A3R2	0.027	0.016	0.17	5	-10000	0	5
SLC9A3R1	0.026	0.005	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.052	0.034	-10000	0	-10000	0	0
FYN	-0.033	0.13	-10000	0	-0.36	65	65
DOK1	-0.005	0.042	0.17	25	-0.17	1	26
HRAS/GTP	0.021	0.012	0.12	6	-10000	0	6
PDGFB	0.027	0.003	-10000	0	-10000	0	0
RAC1	0.037	0.099	0.35	20	-0.33	3	23
PRKCD	-0.004	0.041	0.17	24	-10000	0	24
FER	-0.009	0.044	0.17	18	-0.17	11	29
MAPKKK cascade	0.003	0.083	0.24	41	-10000	0	41
RASA1	-0.004	0.043	0.17	25	-0.17	1	26
NCK1	0.025	0.007	-10000	0	-10000	0	0
NCK2	0.027	0.003	-10000	0	-10000	0	0
p62DOK/Csk	0.033	0.033	0.17	24	-0.16	1	25
PDGFB-D/PDGFRB/SHB	0.038	0.023	-10000	0	-0.22	3	3
chemotaxis	0.007	0.075	0.24	9	-0.26	13	22
STAT1-3-5/STAT1-3-5	0.06	0.026	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.021	0.008	0.12	2	-10000	0	2
PTPRJ	0.026	0.006	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.034	0.019	-10000	0	-10000	0	0
CDKN1B	0.005	0.048	-10000	0	-0.29	10	10
CDKN1A	0.005	0.055	0.19	4	-0.28	13	17
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.023	0.012	0.17	1	-10000	0	1
FOXO3	0.006	0.041	-10000	0	-0.26	10	10
AKT1	0.006	0.053	-10000	0	-0.29	13	13
BAD	0.027	0.008	0.17	1	-10000	0	1
AKT3	0.011	0.012	-10000	0	-0.24	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.005	0.052	-10000	0	-0.28	13	13
AKT1/ASK1	0.031	0.066	0.3	1	-0.26	15	16
BAD/YWHAZ	0.042	0.024	-10000	0	-10000	0	0
RICTOR	0.026	0.005	-10000	0	-10000	0	0
RAF1	0.026	0.005	-10000	0	-10000	0	0
JNK cascade	-0.027	0.061	0.26	15	-10000	0	15
TSC1	0.005	0.043	-10000	0	-0.26	12	12
YWHAZ	0.021	0.011	-10000	0	-10000	0	0
AKT1/RAF1	0.033	0.069	0.27	2	-0.27	15	17
EP300	0.025	0.026	-10000	0	-0.31	3	3
mol:GDP	0.008	0.053	-10000	0	-0.29	13	13
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.004	0.051	-10000	0	-0.28	13	13
YWHAQ	0.027	0.004	-10000	0	-10000	0	0
TBC1D4	0.003	0.003	-10000	0	-10000	0	0
MAP3K5	0.026	0.017	0.17	1	-0.31	1	2
MAPKAP1	0.026	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.028	0.074	0.27	9	-0.22	22	31
YWHAH	0.027	0.004	-10000	0	-10000	0	0
AKT1S1	0.005	0.053	0.19	1	-0.28	13	14
CASP9	0.004	0.052	-10000	0	-0.28	13	13
YWHAB	0.026	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.034	0.071	0.31	9	-0.28	11	20
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.05	0.017	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
SRC	0.026	0.006	-10000	0	-10000	0	0
AKT2/p21CIP1	0.01	0.053	0.19	4	-0.24	13	17
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.009	0.043	-10000	0	-0.33	6	6
CHUK	0.008	0.039	0.19	3	-0.26	8	11
BAD/BCL-XL	0.037	0.066	0.23	5	-0.27	14	19
mTORC2	0.032	0.01	-10000	0	-10000	0	0
AKT2	0.012	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.034	0.09	0.27	18	-0.31	10	28
PDPK1	0.026	0.006	-10000	0	-10000	0	0
MDM2	0.006	0.056	0.19	6	-0.28	13	19
MAPKKK cascade	-0.033	0.068	0.27	15	-0.27	2	17
MDM2/Cbp/p300	0.047	0.082	0.32	14	-0.27	12	26
TSC1/TSC2	0.009	0.071	0.28	16	-0.28	13	29
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.079	0.31	14	-0.26	12	26
glucose import	-0.016	0.041	-10000	0	-0.15	41	41
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.009	0.041	0.18	1	-0.26	4	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.016	0.041	-10000	0	-0.15	41	41
GSK3A	0.005	0.051	-10000	0	-0.29	12	12
FOXO1	0.009	0.028	0.19	2	-0.24	4	6
GSK3B	0.009	0.054	0.19	10	-0.29	10	20
SFN	-0.006	0.1	-10000	0	-0.31	49	49
G1/S transition of mitotic cell cycle	0.012	0.063	0.27	6	-0.3	9	15
p27Kip1/14-3-3 family	0.016	0.048	-10000	0	-0.43	2	2
PRKACA	0.027	0.003	-10000	0	-10000	0	0
KPNA1	0.026	0.006	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
YWHAG	0.025	0.008	-10000	0	-10000	0	0
RHEB	0.025	0.008	-10000	0	-10000	0	0
CREBBP	0.026	0.005	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.026	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.025	0.013	-10000	0	-10000	0	0
DOCK1	0.023	0.03	-10000	0	-0.31	4	4
ITGA4	0.021	0.059	0.17	11	-0.31	13	24
RAC1	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.026	0.067	0.18	10	-0.23	27	37
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.047	0.043	-10000	0	-0.18	13	13
alpha4/beta7 Integrin/Paxillin	0.03	0.056	0.23	3	-0.18	26	29
lamellipodium assembly	-0.017	0.11	-10000	0	-0.4	32	32
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
PI3K	0.031	0.034	-10000	0	-0.24	6	6
ARF6	0.027	0.004	-10000	0	-10000	0	0
TLN1	0.026	0.005	-10000	0	-10000	0	0
PXN	-0.012	0.003	-10000	0	-10000	0	0
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
ARF6/GTP	0.046	0.039	-10000	0	-0.15	13	13
cell adhesion	0.046	0.04	-10000	0	-0.16	12	12
CRKL/CBL	0.037	0.015	-10000	0	-0.21	1	1
alpha4/beta1 Integrin/Paxillin	0.035	0.039	-10000	0	-0.17	13	13
ITGB1	0.026	0.004	-10000	0	-10000	0	0
ITGB7	0.015	0.064	0.17	3	-0.31	18	21
ARF6/GDP	0.026	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.046	0.051	0.24	4	-0.17	17	21
p130Cas/Crk/Dock1	0.04	0.031	-10000	0	-0.18	4	4
VCAM1	0.025	0.039	0.17	8	-0.31	5	13
alpha4/beta1 Integrin/Paxillin/Talin	0.048	0.041	-10000	0	-0.16	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.048	0.042	-10000	0	-0.16	13	13
BCAR1	0.022	0.011	-10000	0	-10000	0	0
mol:GDP	-0.046	0.041	0.16	13	-10000	0	13
CBL	0.025	0.016	-10000	0	-0.31	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GIT1	0.027	0.002	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.048	0.041	-10000	0	-0.16	12	12
Rac1/GTP	-0.021	0.13	-10000	0	-0.45	32	32

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.026	0.006	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.028	0.07	-10000	0	-0.42	2	2
Syndecan-3/Neurocan	0.032	0.04	-10000	0	-0.45	2	2
POMC	-0.006	0.1	0.17	5	-0.31	50	55
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
Syndecan-3/EGFR	0.012	0.053	-10000	0	-0.45	2	2
AGRP	0.02	0.013	0.17	2	-10000	0	2
NCSTN	0.026	0.006	-10000	0	-10000	0	0
PSENEN	0.027	0.003	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.027	0.003	-10000	0	-10000	0	0
APH1A	0.026	0.006	-10000	0	-10000	0	0
NCAN	0.034	0.037	0.17	31	-10000	0	31
long-term memory	0.036	0.036	-10000	0	-0.4	2	2
Syndecan-3/IL8	0.022	0.056	-10000	0	-0.45	2	2
PSEN1	0.026	0.004	-10000	0	-10000	0	0
Src/Cortactin	0.037	0.011	-10000	0	-10000	0	0
FYN	0.022	0.018	-10000	0	-0.31	1	1
limb bud formation	0.01	0.03	-10000	0	-0.46	2	2
MC4R	0.018	0.013	0.17	2	-10000	0	2
SRC	0.026	0.006	-10000	0	-10000	0	0
PTN	-0.022	0.12	0.17	3	-0.31	70	73
FGFR/FGF/Syndecan-3	0.01	0.031	-10000	0	-0.46	2	2
neuron projection morphogenesis	0.012	0.074	0.27	4	-0.41	2	6
Syndecan-3/AgRP	0.023	0.033	-10000	0	-0.44	2	2
Syndecan-3/AgRP/MC4R	0.032	0.036	-10000	0	-0.4	2	2
Fyn/Cortactin	0.032	0.019	-10000	0	-0.21	1	1
SDC3	0.01	0.031	-10000	0	-0.47	2	2
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.021	0.055	-10000	0	-0.44	2	2
IL8	0.01	0.094	0.17	24	-0.31	35	59
Syndecan-3/Fyn/Cortactin	0.037	0.037	-10000	0	-0.41	2	2
Syndecan-3/CASK	0.009	0.029	-10000	0	-0.44	2	2
alpha-MSH/MC4R	0.008	0.076	-10000	0	-0.21	50	50
Gamma Secretase	0.072	0.025	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.004	0.051	-10000	0	-10000	0	0
PLK1	0.027	0.13	0.44	5	-1.1	1	6
CDKN1B	0.051	0.092	0.36	8	-0.32	6	14
FOXO3	0.023	0.12	0.4	1	-0.54	6	7
KAT2B	0.031	0.015	-10000	0	-10000	0	0
FOXO1/SIRT1	0.018	0.052	0.27	1	-10000	0	1
CAT	0.021	0.12	0.44	4	-1	1	5
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
AKT1	0.033	0.015	-10000	0	-10000	0	0
FOXO1	0.008	0.056	0.23	5	-10000	0	5
MAPK10	0.029	0.046	0.19	35	-0.17	1	36
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
FOXO4	0.05	0.082	0.31	22	-0.36	3	25
response to oxidative stress	0.009	0.007	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.026	0.11	0.37	1	-0.75	2	3
XPO1	0.027	0.004	-10000	0	-10000	0	0
EP300	0.026	0.026	-10000	0	-0.31	3	3
BCL2L11	0.013	0.12	-10000	0	-0.8	9	9
FOXO1/SKP2	0.016	0.054	-10000	0	-0.25	3	3
mol:GDP	0.009	0.007	-10000	0	-10000	0	0
RAN	0.027	0.006	-10000	0	-10000	0	0
GADD45A	0.042	0.14	0.35	1	-0.6	13	14
YWHAQ	0.027	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.025	0.069	0.24	1	-0.41	2	3
MST1	0.048	0.049	0.18	55	-0.14	1	56
CSNK1D	0.026	0.005	-10000	0	-10000	0	0
CSNK1E	0.027	0.003	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.006	0.1	-10000	0	-0.41	14	14
YWHAB	0.026	0.005	-10000	0	-10000	0	0
MAPK8	0.028	0.048	0.19	35	-0.19	3	38
MAPK9	0.03	0.047	0.19	38	-10000	0	38
YWHAG	0.025	0.008	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
YWHAZ	0.021	0.011	-10000	0	-10000	0	0
SIRT1	0.025	0.012	-10000	0	-10000	0	0
SOD2	0.049	0.1	0.38	9	-0.53	1	10
RBL2	-0.021	0.23	-10000	0	-0.67	45	45
RAL/GDP	0.038	0.018	-10000	0	-10000	0	0
CHUK	0.03	0.015	-10000	0	-10000	0	0
Ran/GTP	0.021	0.006	-10000	0	-10000	0	0
CSNK1G2	0.026	0.005	-10000	0	-10000	0	0
RAL/GTP	0.04	0.018	-10000	0	-10000	0	0
CSNK1G1	0.027	0.003	-10000	0	-10000	0	0
FASLG	-0.011	0.22	-10000	0	-1.1	18	18
SKP2	0.021	0.04	-10000	0	-0.31	7	7
USP7	0.027	0.005	-10000	0	-10000	0	0
IKBKB	0.025	0.018	-10000	0	-10000	0	0
CCNB1	0.02	0.12	0.45	1	-1	1	2
FOXO1-3a-4/beta catenin	0.06	0.1	0.36	13	-0.4	5	18
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.054	-10000	0	-0.24	3	3
CSNK1A1	0.027	0.004	-10000	0	-10000	0	0
SGK1	-0.012	0.12	0.18	6	-0.3	68	74
CSNK1G3	0.026	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.012	-10000	0	-10000	0	0
ZFAND5	0.051	0.086	0.4	11	-10000	0	11
SFN	-0.006	0.1	-10000	0	-0.31	49	49
CDK2	0.027	0.006	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.01	0.099	-10000	0	-0.4	12	12
CREBBP	0.027	0.006	-10000	0	-10000	0	0
FBXO32	0.056	0.16	0.46	15	-1.1	2	17
BCL6	0.032	0.13	-10000	0	-0.64	10	10
RALB	0.026	0.006	-10000	0	-10000	0	0
RALA	0.025	0.008	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.01	0.086	-10000	0	-0.26	48	48
KLHL20	0.014	0.043	0.16	3	-0.19	1	4
CYFIP2	0.026	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.062	0.34	6	-10000	0	6
ENAH	-0.01	0.085	-10000	0	-0.26	46	46
AP1M1	0.027	0.003	-10000	0	-10000	0	0
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	0.018	0.026	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.021	-10000	0	-0.13	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.048	0.049	-10000	0	-0.16	16	16
RAPGEF1	-0.008	0.079	0.29	4	-10000	0	4
CTNND1	0.027	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.003	0.092	-10000	0	-0.26	55	55
CRK	-0.008	0.076	-10000	0	-0.25	37	37
E-cadherin/gamma catenin/alpha catenin	0.046	0.021	-10000	0	-10000	0	0
alphaE/beta7 Integrin	0.028	0.048	0.14	3	-0.21	18	21
IQGAP1	0.027	0.003	-10000	0	-10000	0	0
NCKAP1	0.026	0.005	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.016	-10000	0	-10000	0	0
DLG1	-0.009	0.084	-10000	0	-0.26	45	45
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.015	-10000	0	-0.16	1	1
MLLT4	0.026	0.005	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.049	0.026	-10000	0	-0.16	3	3
PI3K	-0.019	0.019	-10000	0	-0.2	1	1
ARF6	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.035	0.014	-10000	0	-10000	0	0
TIAM1	0.023	0.03	-10000	0	-0.31	4	4
E-cadherin(dimer)/Ca2+	0.052	0.026	-10000	0	-10000	0	0
AKT1	-0.008	0.027	0.1	5	-0.12	1	6
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
CDH1	0.024	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.069	0.31	11	-10000	0	11
actin cytoskeleton organization	0.015	0.043	0.2	11	-0.14	1	12
CDC42/GDP	0.02	0.072	0.29	16	-10000	0	16
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.015	0.007	-10000	0	-10000	0	0
ITGB7	0.015	0.064	0.17	3	-0.31	18	21
RAC1	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.056	0.028	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.039	0.019	-10000	0	-10000	0	0
mol:GDP	0.007	0.076	0.3	16	-10000	0	16
CDC42/GTP/IQGAP1	0.036	0.006	-10000	0	-10000	0	0
JUP	0.027	0.004	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.021	0.062	0.38	3	-10000	0	3
RAC1/GTP/IQGAP1	0.033	0.011	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.039	0.008	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
CDC42	0.027	0.003	-10000	0	-10000	0	0
CTNNA1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.014	0.037	0.18	11	-0.091	1	12
NME1	0.03	0.022	0.17	11	-10000	0	11
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.008	0.084	-10000	0	-0.26	45	45
regulation of cell-cell adhesion	0.011	0.02	-10000	0	-10000	0	0
WASF2	0.006	0.02	0.08	3	-10000	0	3
Rap1/GTP	0.021	0.036	0.19	11	-10000	0	11
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.056	0.051	-10000	0	-0.15	14	14
CCND1	0.016	0.042	0.21	11	-0.11	1	12
VAV2	0.006	0.088	0.33	1	-0.55	1	2
RAP1/GDP	0.026	0.051	0.26	9	-10000	0	9
adherens junction assembly	-0.008	0.082	-10000	0	-0.25	45	45
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.004	-10000	0	-10000	0	0
PIP5K1C	0.026	0.005	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.041	0.046	-10000	0	-0.16	11	11
E-cadherin/beta catenin	0.011	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.01	0.087	-10000	0	-0.26	48	48
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
Rac1/GTP	0.002	0.045	-10000	0	-0.3	1	1
E-cadherin/beta catenin/alpha catenin	0.045	0.022	-10000	0	-10000	0	0
ITGAE	0.025	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.094	-10000	0	-0.26	55	55

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.041	0.094	0.42	8	-0.38	1	9
RAD9A	0.026	0.009	0.17	1	-10000	0	1
AP1	0	0.098	0.25	1	-0.22	78	79
IFNAR2	0.028	0.006	-10000	0	-10000	0	0
AKT1	0.015	0.029	-10000	0	-0.15	8	8
ER alpha/Oestrogen	0.014	0.041	0.12	1	-0.21	16	17
NFX1/SIN3/HDAC complex	0.022	0.027	-10000	0	-0.24	1	1
EGF	0.024	0.084	0.17	40	-0.31	23	63
SMG5	0.026	0.005	-10000	0	-10000	0	0
SMG6	0.025	0.007	-10000	0	-10000	0	0
SP3/HDAC2	0.037	0.017	-10000	0	-10000	0	0
TERT/c-Abl	0.046	0.089	0.41	6	-10000	0	6
SAP18	0.026	0.006	-10000	0	-10000	0	0
MRN complex	0.041	0.024	-10000	0	-10000	0	0
WT1	0.05	0.12	0.18	152	-0.31	34	186
WRN	0.02	0.012	-10000	0	-10000	0	0
SP1	0.029	0.006	-10000	0	-10000	0	0
SP3	0.027	0.006	-10000	0	-10000	0	0
TERF2IP	0.022	0.011	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.053	0.081	-10000	0	-0.35	1	1
Mad/Max	0.041	0.009	-10000	0	-10000	0	0
TERT	0.041	0.095	0.42	8	-0.38	1	9
CCND1	0.047	0.11	0.58	7	-10000	0	7
MAX	0.027	0.005	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
RBBP4	0.026	0.015	-10000	0	-0.31	1	1
TERF2	0.02	0.011	-10000	0	-10000	0	0
PTGES3	0.027	0.004	-10000	0	-10000	0	0
SIN3A	0.027	0.003	-10000	0	-10000	0	0
Telomerase/911	0.037	0.042	0.23	1	-10000	0	1
CDKN1B	0.01	0.018	-10000	0	-10000	0	0
RAD1	0.026	0.006	-10000	0	-10000	0	0
XRCC5	0.027	0.004	-10000	0	-10000	0	0
XRCC6	0.027	0.004	-10000	0	-10000	0	0
SAP30	0.027	0.005	-10000	0	-10000	0	0
TRF2/PARP2	0.033	0.015	-10000	0	-10000	0	0
UBE3A	0.027	0.005	-10000	0	-10000	0	0
JUN	0.025	0.031	0.17	1	-0.31	4	5
E6	0.001	0.001	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.022	0.004	-10000	0	-10000	0	0
FOS	-0.025	0.12	0.17	4	-0.31	78	82
IFN-gamma/IRF1	0.053	0.037	0.27	4	-10000	0	4
PARP2	0.027	0.004	-10000	0	-10000	0	0
BLM	0.033	0.031	0.17	22	-10000	0	22
Telomerase	0.022	0.035	0.25	1	-0.25	1	2
IRF1	0.033	0.025	0.18	13	-10000	0	13
ESR1	0.016	0.06	0.17	1	-0.31	16	17
KU/TER	0.039	0.008	-10000	0	-10000	0	0
ATM/TRF2	0.033	0.019	-10000	0	-0.22	1	1
ubiquitin-dependent protein catabolic process	0.026	0.033	-10000	0	-0.29	1	1
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.026	0.033	-10000	0	-0.29	1	1
HDAC1	0.027	0.003	-10000	0	-10000	0	0
HDAC2	0.025	0.011	-10000	0	-10000	0	0
ATM	0.016	0.023	-10000	0	-0.29	1	1
SMAD3	-0.014	0.009	-10000	0	-0.21	1	1
ABL1	0.026	0.006	-10000	0	-10000	0	0
MXD1	0.028	0.004	-10000	0	-10000	0	0
MRE11A	0.026	0.006	-10000	0	-10000	0	0
HUS1	0.024	0.008	-10000	0	-10000	0	0
RPS6KB1	0.026	0.005	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.054	0.087	0.4	2	-0.48	1	3
NR2F2	0.025	0.004	-10000	0	-10000	0	0
MAPK3	-0.005	0.013	-10000	0	-10000	0	0
MAPK1	-0.005	0.013	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.025	0.016	-10000	0	-0.31	1	1
NFKB1	0.027	0.004	-10000	0	-10000	0	0
HNRNPC	0.027	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.016	0.023	-10000	0	-0.29	1	1
NBN	0.021	0.011	-10000	0	-10000	0	0
EGFR	-0.001	0.09	-10000	0	-0.31	39	39
mol:Oestrogen	0.001	0	-10000	0	-10000	0	0
EGF/EGFR	0.014	0.092	0.14	34	-0.22	56	90
MYC	0.029	0.035	0.18	24	-10000	0	24
IL2	0.025	0.012	0.18	2	-10000	0	2
KU	0.039	0.008	-10000	0	-10000	0	0
RAD50	0.026	0.005	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
TGFB1	0.025	0.016	-10000	0	-0.31	1	1
TRF2/BLM	0.036	0.022	0.14	10	-10000	0	10
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.058	0.095	0.41	6	-0.36	1	7
SP1/HDAC2	0.038	0.018	-10000	0	-10000	0	0
PINX1	0.02	0.012	-10000	0	-10000	0	0
Telomerase/EST1A	0.05	0.08	-10000	0	-0.35	1	1
Smad3/Myc	0.025	0.028	0.13	24	-0.18	1	25
911 complex	0.047	0.02	-10000	0	-10000	0	0
IFNG	0.036	0.037	0.18	31	-10000	0	31
Telomerase/PinX1	0.038	0.076	-10000	0	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.028	0.057	0.28	4	-0.34	1	5
SIN3B	0.027	0.003	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
Telomerase/EST1B	0.052	0.08	-10000	0	-0.35	1	1
response to DNA damage stimulus	0.006	0.023	0.13	4	-0.1	11	15
MRN complex/TRF2/Rap1	0.051	0.037	-10000	0	-10000	0	0
TRF2/WRN	0.027	0.018	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.053	0.081	-10000	0	-0.35	1	1
E2F1	0.034	0.029	0.18	18	-10000	0	18
ZNFX1	0.026	0.006	-10000	0	-10000	0	0
PIF1	0.028	0.023	0.17	7	-0.31	1	8
NCL	0.027	0.003	-10000	0	-10000	0	0
DKC1	0.027	0.002	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.005	0.051	0.22	2	-0.22	8	10
adherens junction organization	-0.004	0.06	0.2	4	-0.24	9	13
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.065	0.23	2	-0.26	6	8
FMN1	-0.013	0.066	0.15	2	-0.23	18	20
mol:IP3	0.006	0.034	-10000	0	-0.21	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.004	0.058	-10000	0	-0.24	11	11
CTNNB1	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.006	0.043	0.2	1	-0.2	4	5
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.004	0.099	-10000	0	-0.53	7	7
CTNND1	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.002	0.052	0.15	1	-0.23	11	12
VASP	-0.001	0.055	0.15	3	-0.24	9	12
ZYX	-0.001	0.051	-10000	0	-0.25	8	8
JUB	0.001	0.055	0.15	3	-0.23	11	14
EGFR(dimer)	0.003	0.076	-10000	0	-0.25	20	20
E-cadherin/beta catenin-gamma catenin	0.046	0.02	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.024	0.051	0.21	1	-0.21	4	5
PIK3CA	0.024	0.027	-10000	0	-0.31	3	3
PI3K	0.025	0.052	0.21	1	-0.22	4	5
FYN	0	0.05	0.22	1	-0.22	13	14
mol:Ca2+	0.006	0.034	-10000	0	-0.21	3	3
JUP	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.023	0.032	-10000	0	-0.31	4	4
mol:DAG	0.006	0.034	-10000	0	-0.21	3	3
CDH1	0.024	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.072	0.24	3	-0.26	6	9
establishment of polarity of embryonic epithelium	-0.001	0.054	0.15	3	-0.24	9	12
SRC	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
EGFR	-0.002	0.09	-10000	0	-0.31	39	39
CASR	-0.001	0.038	0.16	11	-0.2	3	14
RhoA/GTP	0.02	0.044	-10000	0	-0.2	3	3
AKT2	0.007	0.043	0.19	2	-0.2	4	6
actin cable formation	-0.016	0.066	0.2	3	-0.24	15	18
apoptosis	-0.01	0.054	0.22	4	-0.28	4	8
CTNNA1	0.027	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.059	0.16	14	-0.22	14	28
PIP5K1A	-0.002	0.053	0.15	1	-0.23	11	12
PLCG1	0.006	0.035	-10000	0	-0.22	3	3
Rac1/GTP	0.012	0.077	-10000	0	-0.24	19	19
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.028	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.015	0.083	0.29	5	-0.24	6	11
ERC1	0.025	0.007	-10000	0	-10000	0	0
RIP2/NOD2	0.024	0.042	-10000	0	-0.21	12	12
NFKBIA	-0.004	0.043	0.22	17	-10000	0	17
BIRC2	0.026	0.006	-10000	0	-10000	0	0
IKBKB	0.021	0.011	-10000	0	-10000	0	0
RIPK2	0.021	0.011	-10000	0	-10000	0	0
IKBKG	0.024	0.042	-10000	0	-0.3	1	1
IKK complex/A20	0.023	0.1	-10000	0	-0.3	22	22
NEMO/A20/RIP2	0.021	0.011	-10000	0	-10000	0	0
XPO1	0.027	0.004	-10000	0	-10000	0	0
NEMO/ATM	0.018	0.094	0.26	2	-0.3	22	24
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.026	0.006	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.009	-10000	0	-10000	0	0
IKK complex/ELKS	0.018	0.083	-10000	0	-0.28	20	20
BCL10/MALT1/TRAF6	0.046	0.023	-10000	0	-0.18	1	1
NOD2	0.014	0.06	0.17	2	-0.31	16	18
NFKB1	0.028	0.004	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
MALT1	0.023	0.019	0.17	1	-0.31	1	2
cIAP1/UbcH5C	0.038	0.01	-10000	0	-10000	0	0
ATM	0.025	0.016	-10000	0	-0.31	1	1
TNF/TNFR1A	0.027	0.058	0.14	12	-0.21	24	36
TRAF6	0.026	0.005	-10000	0	-10000	0	0
PRKCA	0.011	0.069	-10000	0	-0.31	22	22
CHUK	0.025	0.007	-10000	0	-10000	0	0
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
TNF	0.014	0.076	0.17	12	-0.31	24	36
NF kappa B1 p50/RelA	0.056	0.017	-10000	0	-10000	0	0
BCL10	0.026	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.043	0.22	17	-10000	0	17
beta TrCP1/SCF ubiquitin ligase complex	0.028	0.005	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
IKK complex	0.021	0.089	-10000	0	-0.29	21	21
CYLD	0.024	0.008	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.023	0.098	-10000	0	-0.3	23	23

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.041	0.02	0.14	13	-10000	0	13
FBXW11	0.026	0.005	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.003	0.058	-10000	0	-0.18	46	46
NF kappa B1 p50/RelA/I kappa B alpha	0.023	0.029	-10000	0	-10000	0	0
NFKBIA	0.011	0.024	0.12	12	-0.16	4	16
MAPK14	0.027	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.021	0.012	-10000	0	-10000	0	0
ARRB2	0.012	0.004	-10000	0	-10000	0	0
REL	-0.005	0.097	-10000	0	-0.31	46	46
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0.023	0.14	12	-10000	0	12
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.012	-10000	0	-10000	0	0
PIK3CA	0.023	0.027	-10000	0	-0.31	3	3
NF kappa B1 p50 dimer	0.016	0.02	0.25	3	-10000	0	3
PIK3R1	0.022	0.031	-10000	0	-0.31	4	4
NFKB1	-0.01	0.005	-10000	0	-10000	0	0
RELA	0.026	0.006	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.015	0.03	-10000	0	-0.16	4	4
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.024	0.029	-10000	0	-10000	0	0
SRC	0.026	0.006	-10000	0	-10000	0	0
PI3K	0.031	0.034	-10000	0	-0.24	6	6
NF kappa B1 p50/RelA	0.015	0.03	-10000	0	-0.16	4	4
IKBKB	0.021	0.011	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.005	-10000	0	-10000	0	0
SYK	0.023	0.035	0.17	1	-0.31	5	6
I kappa B alpha/PIK3R1	0.028	0.037	0.21	7	-0.15	5	12
cell death	0.023	0.028	-10000	0	-10000	0	0
NF kappa B1 p105/c-Rel	0.003	0.058	-10000	0	-0.18	46	46
LCK	0.03	0.02	0.17	9	-10000	0	9
BCL3	0.031	0.024	0.17	13	-10000	0	13

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.019	0.014	0.11	1	-0.087	6	7
TRAF2/ASK1	0.034	0.014	0.13	1	-0.18	1	2
ATM	0.025	0.016	-10000	0	-0.31	1	1
MAP2K3	-0.021	0.11	0.31	6	-0.33	33	39
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.012	0.092	0.3	5	-0.3	21	26
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.041	0.048	0.17	52	-0.31	1	53
TXN	0.006	0.002	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
GADD45A	0.025	0.022	-10000	0	-0.31	2	2
GADD45B	0.031	0.033	0.17	19	-0.31	1	20
MAP3K1	0.023	0.017	-10000	0	-0.31	1	1
MAP3K6	0.027	0.002	-10000	0	-10000	0	0
MAP3K7	0.022	0.01	-10000	0	-10000	0	0
MAP3K4	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.039	0.014	0.14	1	-0.21	1	2
TAK1/TAB family	-0.002	0.011	-10000	0	-0.13	2	2
RAC1/OSM/MEKK3	0.046	0.018	-10000	0	-10000	0	0
TRAF2	0.026	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.004	0.088	-10000	0	-0.28	24	24
TRAF6	0.006	0.001	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.031	0.041	0.17	26	-0.31	2	28
CCM2	0.025	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.036	0.028	0.13	25	-0.18	2	27
MAPK11	0.029	0.019	0.17	8	-10000	0	8
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.049	0.032	-10000	0	-0.16	3	3
OSM/MEKK3	0.036	0.013	-10000	0	-10000	0	0
TAOK1	-0.03	0.094	-10000	0	-0.24	81	81
TAOK2	0.011	0.012	-10000	0	-0.24	1	1
TAOK3	0.011	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.026	0.017	0.17	1	-0.31	1	2
MAP3K10	0.027	0.004	-10000	0	-10000	0	0
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.023	0.012	0.13	1	-0.16	1	2
GADD45/MTK1/MTK1	0.069	0.045	0.22	15	-0.15	3	18

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.017	0.023	-10000	0	-0.18	9	9
SNTA1	0.026	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.016	0.026	0.2	2	-0.18	8	10
MAPK12	-0.009	0.019	0.17	2	-0.15	4	6
CCND1	0.009	0.017	-10000	0	-10000	0	0
p38 gamma/SNTA1	0.014	0.033	0.19	11	-0.16	3	14
MAP2K3	0.026	0.005	-10000	0	-10000	0	0
PKN1	0.029	0.019	0.17	8	-10000	0	8
G2/M transition checkpoint	-0.009	0.019	0.17	2	-0.15	4	6
MAP2K6	-0.004	0.018	0.23	1	-0.16	4	5
MAPT	-0.003	0.049	0.21	6	-0.17	10	16
MAPK13	-0.015	0.027	-10000	0	-0.21	9	9
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.004	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.028	0.015	-10000	0	-0.17	5	5
PI3K Class IB/PDE3B	0.028	0.015	0.17	5	-10000	0	5
PDE3B	0.028	0.015	0.17	5	-10000	0	5

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.058	0.034	-10000	0	-0.16	6	6
HDAC3	0.026	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.013	0.004	-10000	0	-10000	0	0
GATA1/HDAC4	0.038	0.014	-10000	0	-0.21	1	1
GATA1/HDAC5	0.036	0.015	0.14	1	-0.18	1	2
GATA2/HDAC5	0.034	0.015	0.14	1	-10000	0	1
HDAC5/BCL6/BCoR	0.048	0.019	-10000	0	-10000	0	0
HDAC9	0.008	0.084	0.17	13	-0.31	30	43
Glucocorticoid receptor/Hsp90/HDAC6	0.047	0.036	-10000	0	-0.18	10	10
HDAC4/ANKRA2	0.036	0.012	-10000	0	-10000	0	0
HDAC5/YWHAB	0.036	0.012	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.012	0.006	0.1	1	-10000	0	1
GATA2	0.025	0.01	0.17	1	-10000	0	1
HDAC4/RFXANK	0.041	0.014	-10000	0	-10000	0	0
BCOR	0.027	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.028	0.014	0.17	4	-10000	0	4
HDAC5	0.025	0.007	-10000	0	-10000	0	0
GNB1/GNG2	0.036	0.029	-10000	0	-0.21	6	6
Histones	0.015	0.055	0.21	1	-0.22	5	6
ADRBK1	0.026	0.006	-10000	0	-10000	0	0
HDAC4	0.027	0.004	-10000	0	-10000	0	0
XPO1	0.027	0.004	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.034	0.015	-10000	0	-10000	0	0
HDAC4/Ubc9	0.038	0.01	-10000	0	-10000	0	0
HDAC7	0.027	0.004	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.035	0.014	-10000	0	-10000	0	0
TUBA1B	0.027	0.003	-10000	0	-10000	0	0
HDAC6	0.027	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.039	0.017	0.14	7	-10000	0	7
CAMK4	0.006	0.078	0.17	1	-0.31	28	29
Tubulin/HDAC6	0.061	0.031	-10000	0	-10000	0	0
SUMO1	0.027	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.026	0.005	-10000	0	-10000	0	0
GATA1	0.025	0.017	0.17	1	-0.31	1	2
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
NR3C1	0.019	0.05	-10000	0	-0.31	11	11
SUMO1/HDAC4	0.041	0.024	-10000	0	-10000	0	0
SRF	0.027	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.038	0.009	-10000	0	-10000	0	0
Tubulin	0.048	0.032	0.14	46	-10000	0	46
HDAC4/14-3-3 E	0.037	0.012	-10000	0	-10000	0	0
GNB1	0.027	0.004	-10000	0	-10000	0	0
RANGAP1	0.028	0.012	0.17	3	-10000	0	3
BCL6/BCoR	0.037	0.011	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.049	0.017	-10000	0	-10000	0	0
HDAC4/SRF	0.036	0.056	-10000	0	-0.18	28	28
HDAC4/ER alpha	0.031	0.045	0.14	1	-0.21	16	17
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.015	0.055	0.21	1	-0.21	5	6
cell motility	0.06	0.031	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
HDAC7/HDAC3	0.038	0.009	-10000	0	-10000	0	0
BCL6	0.025	0.007	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.027	0.004	-10000	0	-10000	0	0
Hsp90/HDAC6	0.039	0.008	-10000	0	-10000	0	0
ESR1	0.016	0.06	0.17	1	-0.31	16	17
HDAC6/HDAC11	0.039	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.04	0.027	-10000	0	-10000	0	0
NPC	0.016	0.004	-10000	0	-10000	0	0
MEF2C	0.024	0.024	0.17	2	-0.31	2	4
RAN	0.026	0.006	-10000	0	-10000	0	0
HDAC4/MEF2C	0.065	0.035	-10000	0	-0.15	2	2
GNG2	0.023	0.037	-10000	0	-0.31	6	6
NCOR2	0.026	0.006	-10000	0	-10000	0	0
TUBB2A	0.04	0.043	0.17	46	-10000	0	46
HDAC11	0.026	0.005	-10000	0	-10000	0	0
HSP90AA1	0.026	0.005	-10000	0	-10000	0	0
RANBP2	0.027	0.008	0.17	1	-10000	0	1
ANKRA2	0.025	0.008	-10000	0	-10000	0	0
RFXANK	0.029	0.018	0.17	7	-10000	0	7
nuclear import	-0.028	0.013	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0.021	0.034	-10000	0	-0.31	5	5
PLK4	0.027	0.013	0.17	3	-10000	0	3
regulation of centriole replication	-0.013	0.021	-10000	0	-0.21	5	5

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.037	0.031	-10000	0	-10000	0	0
CLOCK	0.001	0.091	-10000	0	-0.31	40	40
TIMELESS/CRY2	0.028	0.027	-10000	0	-10000	0	0
DEC1/BMAL1	0.032	0.019	0.14	1	-0.22	2	3
ATR	0.025	0.007	-10000	0	-10000	0	0
NR1D1	0.012	0.017	-10000	0	-10000	0	0
ARNTL	0.027	0.022	-10000	0	-0.31	2	2
TIMELESS	0.012	0.018	-10000	0	-10000	0	0
NPAS2	0.028	0.017	0.18	1	-0.31	1	2
CRY2	0.026	0.005	-10000	0	-10000	0	0
mol:CO	-0.007	0.001	-10000	0	-10000	0	0
CHEK1	0.026	0.006	-10000	0	-10000	0	0
mol:HEME	0.007	0.001	-10000	0	-10000	0	0
PER1	0.019	0.043	-10000	0	-0.31	8	8
BMAL/CLOCK/NPAS2	0.039	0.068	-10000	0	-0.18	42	42
BMAL1/CLOCK	-0.006	0.093	-10000	0	-0.39	3	3
S phase of mitotic cell cycle	0.037	0.031	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.037	0.032	-10000	0	-10000	0	0
mol:NADPH	0.007	0.001	-10000	0	-10000	0	0
PER1/TIMELESS	0.026	0.028	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.018	0.009	0.17	1	-10000	0	1

×

Insulin-mediated glucose transport

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.003	0.1	-10000	0	-0.34	11	11
CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
AKT1	0.026	0.005	-10000	0	-10000	0	0
AKT2	0.027	0.004	-10000	0	-10000	0	0
STXBP4	0.026	0.016	-10000	0	-0.31	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.01	0.1	0.2	1	-0.37	12	13
YWHAZ	0.021	0.011	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
YWHAQ	0.027	0.004	-10000	0	-10000	0	0
TBC1D4	-0.011	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.004	-10000	0	-10000	0	0
YWHAB	0.026	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.046	0.022	-10000	0	-0.18	1	1
YWHAG	0.025	0.008	-10000	0	-10000	0	0
ASIP	0.022	0.033	0.17	4	-0.31	4	8
PRKCI	0.025	0.01	0.17	1	-10000	0	1
AS160/CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
RHOQ	0.026	0.005	-10000	0	-10000	0	0
GYS1	0.008	0.018	0.24	3	-10000	0	3
PRKCZ	0.027	0.004	-10000	0	-10000	0	0
TRIP10	0.027	0.004	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.035	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.008	0.053	-10000	0	-0.23	7	7
VAMP2	0.024	0.009	-10000	0	-10000	0	0
SLC2A4	-0.013	0.11	-10000	0	-0.42	12	12
STX4	0.026	0.005	-10000	0	-10000	0	0
GSK3B	0.017	0.006	-10000	0	-10000	0	0
SFN	-0.006	0.1	-10000	0	-0.31	49	49
LNPEP	0.006	0.076	-10000	0	-0.31	27	27
YWHAE	0.025	0.007	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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
TNFSF10	0.024	0.023	0.17	1	-0.31	2	3
positive regulation of NF-kappaB transcription factor activity	0.022	0.039	-10000	0	-0.21	10	10
MAP2K4	0.012	0.031	-10000	0	-0.22	3	3
IKBKB	0.021	0.011	-10000	0	-10000	0	0
TNFRSF10B	0.019	0.013	-10000	0	-10000	0	0
TNFRSF10A	0.017	0.028	-10000	0	-0.31	3	3
SMPD1	0.008	0.009	-10000	0	-0.13	1	1
IKBKG	0.027	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.012	0.048	-10000	0	-0.31	10	10
TRAIL/TRAILR2	0.026	0.024	0.14	1	-0.18	2	3
TRAIL/TRAILR3	0.016	0.053	0.14	2	-0.21	22	24
TRAIL/TRAILR1	0.024	0.03	0.14	1	-0.2	5	6
TRAIL/TRAILR4	0.022	0.039	-10000	0	-0.21	10	10
TRAIL/TRAILR1/DAP3/GTP	0.032	0.031	-10000	0	-0.16	4	4
IKK complex	0.002	0.057	-10000	0	-0.26	1	1
RIPK1	0.026	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.019	0.004	-10000	0	-10000	0	0
MAPK3	-0.011	0.022	0.26	2	-0.21	2	4
MAP3K1	0.015	0.024	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.012	0.048	-10000	0	-0.31	10	10
TRADD	0.024	0.009	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.017	0.028	-10000	0	-0.31	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.016	0.02	-10000	0	-0.18	3	3
CFLAR	0.027	0.003	-10000	0	-10000	0	0
MAPK1	-0.011	0.02	0.26	2	-0.21	1	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.047	0.044	-10000	0	-0.15	4	4
mol:ceramide	0.008	0.009	-10000	0	-0.12	1	1
FADD	0.026	0.006	-10000	0	-10000	0	0
MAPK8	0.007	0.037	-10000	0	-0.21	5	5
TRAF2	0.026	0.006	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.005	0.066	0.17	1	-0.31	20	21
CHUK	0.025	0.007	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.033	0.034	-10000	0	-0.17	5	5
DAP3	0.026	0.006	-10000	0	-10000	0	0
CASP10	0.005	0.053	0.17	33	-0.22	4	37
JNK cascade	0.022	0.039	-10000	0	-0.21	10	10
TRAIL (trimer)	0.024	0.023	0.17	1	-0.31	2	3
TNFRSF10C	0.005	0.066	0.17	1	-0.31	20	21
TRAIL/TRAILR1/DAP3/GTP/FADD	0.038	0.036	-10000	0	-0.15	4	4
TRAIL/TRAILR2/FADD	0.035	0.03	-10000	0	-0.15	2	2
cell death	0.008	0.009	-10000	0	-0.12	1	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.017	0.014	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.019	0.013	-10000	0	-10000	0	0
CASP8	0.015	0.012	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.049	0.041	-10000	0	-0.13	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.025	0.008	-10000	0	-10000	0	0
SMAD2	0.013	0.043	0.19	10	-0.2	2	12
SMAD3	0.02	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4	0.033	0.038	-10000	0	-0.32	4	4
SMAD4/Ubc9/PIASy	0.047	0.02	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.053	0.042	0.28	1	-10000	0	1
PPM1A	0.027	0.004	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.022	0.036	0.18	5	-0.18	2	7
MAP3K1	0.023	0.017	-10000	0	-0.31	1	1
TRAP-1/SMAD4	0.022	0.058	-10000	0	-0.21	27	27
MAPK3	0.026	0.005	-10000	0	-10000	0	0
MAPK1	0.027	0.004	-10000	0	-10000	0	0
NUP214	0.026	0.006	-10000	0	-10000	0	0
CTDSP1	0.027	0.003	-10000	0	-10000	0	0
CTDSP2	0.027	0.004	-10000	0	-10000	0	0
CTDSPL	0.026	0.005	-10000	0	-10000	0	0
KPNB1	0.026	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.008	0.076	-10000	0	-0.31	27	27
UBE2I	0.026	0.006	-10000	0	-10000	0	0
NUP153	0.026	0.016	-10000	0	-0.31	1	1
KPNA2	0.028	0.015	0.17	5	-10000	0	5
PIAS4	0.027	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.046	0.071	-10000	0	-0.22	21	21
Ran/GTP/Exportin 1/HDAC1	-0.013	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.02	0.072	0.22	1	-0.23	22	23
SUMO1	0.027	0.003	-10000	0	-10000	0	0
ZFPM1	0.022	0.011	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.012	0.006	0.1	1	-10000	0	1
FKBP3	0.027	0.003	-10000	0	-10000	0	0
Histones	0.043	0.051	-10000	0	-10000	0	0
YY1/LSF	0.029	0.033	-10000	0	-0.18	4	4
SMG5	0.026	0.005	-10000	0	-10000	0	0
RAN	0.026	0.006	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.013	0.043	0.16	1	-0.18	23	24
I kappa B alpha/HDAC1	0.024	0.041	-10000	0	-10000	0	0
SAP18	0.026	0.006	-10000	0	-10000	0	0
RELA	0.008	0.044	-10000	0	-0.18	3	3
HDAC1/Smad7	0.044	0.022	-10000	0	-10000	0	0
RANGAP1	0.028	0.012	0.17	3	-10000	0	3
HDAC3/TR2	0.023	0.042	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.004	0.05	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.026	0.063	0.25	5	-0.2	2	7
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.025	0.01	0.17	1	-10000	0	1
GATA1	0.025	0.017	0.17	1	-0.31	1	2
Mad/Max	0.039	0.008	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.004	0.068	-10000	0	-0.24	8	8
RBBP7	0.026	0.004	-10000	0	-10000	0	0
NPC	0.016	0.004	-10000	0	-10000	0	0
RBBP4	0.026	0.015	-10000	0	-0.31	1	1
MAX	0.026	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.026	0.005	-10000	0	-10000	0	0
NFKBIA	0.012	0.033	0.14	1	-10000	0	1
KAT2B	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.018	0.021	-10000	0	-10000	0	0
SIN3 complex	0.064	0.02	-10000	0	-10000	0	0
SMURF1	0.024	0.008	-10000	0	-10000	0	0
CHD3	0.023	0.01	-10000	0	-10000	0	0
SAP30	0.026	0.005	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.025	0.007	-10000	0	-10000	0	0
YY1/HDAC3	0.018	0.038	-10000	0	-10000	0	0
YY1/HDAC2	0.026	0.033	-10000	0	-0.18	4	4
YY1/HDAC1	0.03	0.034	-10000	0	-0.18	4	4
NuRD/MBD2 Complex (MeCP1)	0.005	0.049	-10000	0	-10000	0	0
PPARG	-0.006	0.084	0.18	2	-0.26	42	44
HDAC8/hEST1B	0.052	0.013	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.005	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.024	0.041	-10000	0	-10000	0	0
MBD3L2	0.018	0.003	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.044	0.022	-10000	0	-10000	0	0
CREBBP	0.026	0.005	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.008	0.053	-10000	0	-0.21	6	6
HDAC1	0.027	0.003	-10000	0	-10000	0	0
HDAC3	0.012	0.033	0.14	1	-10000	0	1
HDAC2	0.023	0.01	-10000	0	-10000	0	0
YY1	0.014	0.018	-10000	0	-0.21	3	3
HDAC8	0.027	0.002	-10000	0	-10000	0	0
SMAD7	0.025	0.008	-10000	0	-10000	0	0
NCOR2	0.026	0.006	-10000	0	-10000	0	0
MXD1	0.027	0.003	-10000	0	-10000	0	0
STAT3	0.016	0.021	-10000	0	-0.24	3	3
NFKB1	0.027	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.008	0.17	1	-10000	0	1
YY1/LSF/HDAC1	0.044	0.036	-10000	0	-0.17	4	4
YY1/SAP30/HDAC1	0.044	0.036	-10000	0	-0.17	4	4
EP300	0.025	0.026	-10000	0	-0.31	3	3
STAT3 (dimer non-phopshorylated)	0.016	0.021	-10000	0	-0.24	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.033	0.14	1	-10000	0	1
histone deacetylation	0.001	0.057	-10000	0	-0.24	8	8
STAT3 (dimer non-phopshorylated)/HDAC3	0.015	0.039	-10000	0	-0.19	1	1
nuclear export	-0.052	0.012	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GATAD2B	0.026	0.006	-10000	0	-10000	0	0
GATAD2A	0.027	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.022	0.042	-10000	0	-10000	0	0
GATA1/HDAC1	0.038	0.014	0.14	1	-0.21	1	2
GATA1/HDAC3	0.023	0.044	-10000	0	-10000	0	0
CHD4	0.025	0.007	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.027	0.058	0.14	12	-0.21	24	36
SIN3/HDAC complex/Mad/Max	0.015	0.04	-10000	0	-0.33	1	1
NuRD Complex	0.003	0.064	-10000	0	-0.22	12	12
positive regulation of chromatin silencing	0.041	0.05	-10000	0	-10000	0	0
SIN3B	0.027	0.003	-10000	0	-10000	0	0
MTA2	0.026	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.003	-10000	0	-10000	0	0
XPO1	0.027	0.004	-10000	0	-10000	0	0
SUMO1/HDAC1	0.041	0.024	-10000	0	-10000	0	0
HDAC complex	0.058	0.028	-10000	0	-0.17	1	1
GATA1/Fog1	0.031	0.018	-10000	0	-0.18	1	1
FKBP25/HDAC1/HDAC2	0.046	0.02	-10000	0	-10000	0	0
TNF	0.014	0.076	0.17	12	-0.31	24	36
negative regulation of cell growth	0.014	0.043	-10000	0	-0.27	3	3
NuRD/MBD2/PRMT5 Complex	0.005	0.049	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.04	0.027	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.006	0.066	0.22	1	-0.23	23	24
SIN3/HDAC complex/NCoR1	0.015	0.038	-10000	0	-0.24	1	1
TFCP2	0.026	0.005	-10000	0	-10000	0	0
NR2C1	0.026	0.006	-10000	0	-10000	0	0
MBD3	0.027	0.01	0.17	2	-10000	0	2
MBD2	0.025	0.01	0.17	1	-10000	0	1

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.023	0.12	0.17	1	-0.31	68	69
CLTC	0.022	0.029	0.25	2	-10000	0	2
calcium ion-dependent exocytosis	0.012	0.034	0.2	2	-0.15	3	5
Dynamin 2/GTP	0.023	0.012	-10000	0	-10000	0	0
EXOC4	0.024	0.008	-10000	0	-10000	0	0
CD59	0.013	0.017	-10000	0	-10000	0	0
CPE	0.01	0.017	-10000	0	-0.18	4	4
CTNNB1	0.026	0.005	-10000	0	-10000	0	0
membrane fusion	0.011	0.03	-10000	0	-10000	0	0
CTNND1	-0.01	0.036	0.19	14	-10000	0	14
DNM2	0.027	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.016	0.035	0.22	6	-10000	0	6
TSHR	0.006	0.032	-10000	0	-0.18	13	13
INS	0.013	0.046	-10000	0	-0.44	4	4
BIN1	0.026	0.011	0.17	2	-10000	0	2
mol:Choline	0.011	0.03	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.009	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.022	0.012	-10000	0	-10000	0	0
JUP	0.013	0.017	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.048	0.016	-10000	0	-10000	0	0
ARF6/GTP	0.02	0.003	-10000	0	-10000	0	0
CDH1	0.012	0.017	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.02	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.026	0.011	0.17	2	-10000	0	2
positive regulation of endocytosis	0.02	0.003	-10000	0	-10000	0	0
EXOC2	0.026	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.013	0.041	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.026	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.04	0.029	-10000	0	-0.25	1	1
positive regulation of phagocytosis	0.012	0.002	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.035	0.011	0.13	2	-10000	0	2
ACAP1	0.018	0.034	0.17	8	-0.14	1	9
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.014	0.058	-10000	0	-0.18	1	1
clathrin heavy chain/ACAP1	0.02	0.037	0.22	6	-10000	0	6
JIP4/KLC1	0.05	0.012	-10000	0	-10000	0	0
EXOC1	0.027	0.004	-10000	0	-10000	0	0
exocyst	0.017	0.027	-10000	0	-0.17	6	6
RALA/GTP	0.018	0.006	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.007	-10000	0	-10000	0	0
receptor recycling	0.02	0.003	-10000	0	-10000	0	0
CTNNA1	-0.01	0.033	0.18	14	-10000	0	14
NME1	0.013	0.009	-10000	0	-10000	0	0
clathrin coat assembly	0.023	0.032	0.25	2	-10000	0	2
IL2RA	0.013	0.024	-10000	0	-0.18	1	1
VAMP3	0.012	0.002	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.011	0.055	-10000	0	-0.18	6	6
EXOC6	0.025	0.008	-10000	0	-10000	0	0
PLD1	0.003	0.041	-10000	0	-0.22	16	16
PLD2	0.011	0.005	-10000	0	-10000	0	0
EXOC5	0.027	0.004	-10000	0	-10000	0	0
PIP5K1C	0.013	0.023	0.17	3	-10000	0	3
SDC1	0.008	0.035	-10000	0	-0.18	5	5
ARF6/GDP	0.024	0.006	-10000	0	-10000	0	0
EXOC7	0.026	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.043	0.03	0.26	1	-10000	0	1
mol:Phosphatidic acid	0.011	0.03	-10000	0	-10000	0	0
endocytosis	-0.046	0.016	-10000	0	-10000	0	0
SCAMP2	0.027	0.003	-10000	0	-10000	0	0
ADRB2	0.023	0.047	0.27	10	-10000	0	10
EXOC3	0.026	0.005	-10000	0	-10000	0	0
ASAP2	0.027	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.029	0.01	-10000	0	-10000	0	0
KLC1	0.026	0.005	-10000	0	-10000	0	0
AVPR2	0.018	0.038	0.22	4	-0.26	1	5
RALA	0.024	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.036	0.036	0.24	1	-10000	0	1

×

Arf1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.008	0.029	0.15	16	-0.17	1	17
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.004	0.042	0.15	5	-0.22	5	10
AP2	0.037	0.011	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.033	0.013	-10000	0	-10000	0	0
CLTB	0.027	0.008	0.17	1	-10000	0	1
coatomer protein complex/ARF1/GTP/ER cargo protein	0.016	0.007	-10000	0	-10000	0	0
CD4	0.025	0.027	0.17	5	-0.31	2	7
CLTA	0.026	0.004	-10000	0	-10000	0	0
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
ARFGAP1	-0.006	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.004	0.007	-10000	0	-10000	0	0
ARF1/GTP	0.032	0.014	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.005	0.016	-10000	0	-10000	0	0
mol:Choline	0.003	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.027	0.009	-10000	0	-10000	0	0
DDEF1	0.002	0.006	-10000	0	-10000	0	0
ARF1/GDP	0.002	0.015	-10000	0	-0.11	5	5
AP2M1	0.025	0.007	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.01	0.006	-10000	0	-10000	0	0
Rac/GTP	0.018	0.009	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.035	0.014	-10000	0	-10000	0	0
ARFIP2	0.021	0.017	-10000	0	-10000	0	0
COPA	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.01	0.026	0.13	4	-0.14	3	7
ARF1/GTP/ARHGAP10	0.017	0.007	-10000	0	-10000	0	0
GGA3	0.026	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.015	0.046	-10000	0	-0.23	16	16
AP2A1	0.027	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.013	0.006	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.013	0.052	-10000	0	-0.26	16	16
Arfaptin 2/Rac/GDP	0.032	0.013	-10000	0	-10000	0	0
CYTH2	0.027	0.01	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.034	0.012	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.018	0.006	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.013	0.027	-10000	0	-0.16	4	4
PLD2	0.003	0.007	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.006	0.003	-10000	0	-10000	0	0
PIP5K1A	0.004	0.007	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.013	0.024	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.003	0.007	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.006	0.003	-10000	0	-10000	0	0
GOSR2	0.001	0.054	-10000	0	-0.31	14	14
USO1	0.01	0.016	-10000	0	-0.33	1	1
GBF1	-0.002	0.063	-10000	0	-0.32	19	19
ARF1/GTP/Arfaptin 2	0.035	0.013	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.048	0.026	-10000	0	-0.18	2	2

×

Arf6 downstream pathway

Figure S128. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S128. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.021	0.012	-10000	0	-10000	0	0
regulation of axonogenesis	-0.006	0.019	-10000	0	-10000	0	0
myoblast fusion	-0.026	0.024	-10000	0	-10000	0	0
mol:GTP	0.024	0.008	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.053	0.029	0.16	3	-10000	0	3
ARF1/GTP	0.037	0.012	-10000	0	-10000	0	0
mol:GM1	0.011	0.006	-10000	0	-10000	0	0
mol:Choline	0.002	0.029	-10000	0	-0.16	14	14
lamellipodium assembly	0.016	0.017	-10000	0	-10000	0	0
MAPK3	0.023	0.009	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.054	0.029	-10000	0	-0.16	3	3
ARF1	0.026	0.006	-10000	0	-10000	0	0
ARF6/GDP	0.026	0.024	-10000	0	-10000	0	0
ARF1/GDP	0.032	0.022	-10000	0	-10000	0	0
ARF6	0.035	0.008	-10000	0	-10000	0	0
RAB11A	0.027	0.003	-10000	0	-10000	0	0
TIAM1	0.024	0.03	-10000	0	-0.3	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.009	-10000	0	-10000	0	0
actin filament bundle formation	-0.035	0.018	-10000	0	-10000	0	0
KALRN	0.013	0.013	0.19	1	-10000	0	1
RAB11FIP3/RAB11A	0.038	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.036	0.018	-10000	0	-10000	0	0
NME1	0.03	0.022	0.17	11	-10000	0	11
Rac1/GDP	0.034	0.019	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.024	0.008	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.016	0.017	-10000	0	-10000	0	0
RAC1	0.025	0.008	-10000	0	-10000	0	0
liver development	0.024	0.008	-10000	0	-10000	0	0
ARF6/GTP	0.024	0.008	-10000	0	-10000	0	0
RhoA/GTP	0.038	0.011	-10000	0	-10000	0	0
mol:GDP	0.014	0.008	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.052	0.015	-10000	0	-10000	0	0
RHOA	0.026	0.005	-10000	0	-10000	0	0
PLD1	0.011	0.038	-10000	0	-0.19	17	17
RAB11FIP3	0.026	0.006	-10000	0	-10000	0	0
tube morphogenesis	0.016	0.017	-10000	0	-10000	0	0
ruffle organization	0.006	0.019	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.024	0.008	-10000	0	-10000	0	0
PLD2	0.019	0.008	-10000	0	-10000	0	0
PIP5K1A	0.006	0.019	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.002	0.029	-10000	0	-0.16	14	14
Rac1/GTP	0.016	0.018	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.011	0.006	-10000	0	-10000	0	0
MDM2/SUMO1	0.04	0.024	-10000	0	-10000	0	0
HDAC4	0.027	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.011	0.006	-10000	0	-10000	0	0
SUMO1	0.027	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.01	0.013	0.099	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.007	0.004	0.091	1	-10000	0	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.026	0.006	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.008	0.17	1	-10000	0	1
SUMO1/HDAC4	0.041	0.024	-10000	0	-10000	0	0
SUMO1/HDAC1	0.041	0.024	-10000	0	-10000	0	0
RANGAP1	0.028	0.012	0.17	3	-10000	0	3
MDM2/SUMO1/SUMO1	0.059	0.027	-10000	0	-0.17	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.012	0.006	0.1	1	-10000	0	1
Ran/GTP	0.027	0.024	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.026	0.006	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.025	0.25	1	-10000	0	1
NPC	0.016	0.004	0.098	1	-10000	0	1
PIAS2	0.025	0.008	-10000	0	-10000	0	0
PIAS1	0.026	0.015	-10000	0	-0.31	1	1
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.046	0.02	-9999	-9999
E-cadherin/beta catenin	0.034	0.015	-9999	-9999
CTNNB1	0.026	0.005	-9999	-9999
JUP	0.027	0.004	-9999	-9999
CDH1	0.024	0.009	-9999	-9999

×

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	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.036	0.013	-10000	0	-9999	0
FBXW11	0.026	0.005	-10000	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.005	-10000	0	-9999	0
CHUK	0.025	0.007	-10000	0	-9999	0
NF kappa B2 p100/RelB	0.07	0.029	-10000	0	-9999	0
NFKB1	0.027	0.004	-10000	0	-9999	0
MAP3K14	0.026	0.006	-10000	0	-9999	0
NF kappa B1 p50/RelB	0.039	0.008	-10000	0	-9999	0
RELB	0.027	0.004	-10000	0	-9999	0
NFKB2	0.026	0.013	0.17	3	-9999	3
NF kappa B2 p52/RelB	0.035	0.012	0.13	3	-9999	3
regulation of B cell activation	0.034	0.012	0.13	3	-9999	3

pid_entity	TCGA.ZG.A9NI	TCGA.ZG.A9ND	TCGA.ZG.A9N3	TCGA.ZG.A9MC
109_MAP3K5	0.2	-0.21	-0.053	0.12
47_PPARGC1A	0.027	0	0.027	0.027
105_BMP4	0.027	0.027	-0.31	0.027
105_BMP6	0	0.027	0	0.027
105_BMP7	0.027	-0.31	0	0.027
105_BMP2	0.027	0.027	0	0.027
131_RELN/VLDLR	0	0.16	0	0.07
30_TGFB1/TGF beta receptor Type II	0.027	0.027	0.026	0.027
84_STAT5B	-0.034	-0.015	0.099	0.044
84_STAT5A	-0.034	-0.015	0.099	0.044