PARADIGM pathway analysis of mRNASeq expression data - Uveal Melanoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
IL12-mediated signaling events	20
TCR signaling in naïve CD8+ T cells	20
IL23-mediated signaling events	19
Endothelins	16
Syndecan-1-mediated signaling events	14
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	14
Signaling events regulated by Ret tyrosine kinase	12
Glucocorticoid receptor regulatory network	11
HIF-1-alpha transcription factor network	10
IL4-mediated signaling events	10

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
IL12-mediated signaling events	0.2500	20	1768	87	-0.34	0.058	1000	-1000	-0.075	-1000
TCR signaling in naïve CD8+ T cells	0.2500	20	1899	93	-0.19	0.085	1000	-1000	-0.019	-1000
IL23-mediated signaling events	0.2375	19	1172	60	-0.22	0.14	1000	-1000	-0.069	-1000
Endothelins	0.2000	16	1539	96	-0.066	0.031	1000	-1000	-0.007	-1000
Syndecan-1-mediated signaling events	0.1750	14	493	34	-0.037	0.01	1000	-1000	-0.005	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1750	14	954	68	-0.14	0.057	1000	-1000	-0.034	-1000
Signaling events regulated by Ret tyrosine kinase	0.1500	12	1051	82	-0.057	0.01	1000	-1000	-0.02	-1000
Glucocorticoid receptor regulatory network	0.1375	11	1271	114	-0.3	0.16	1000	-1000	-0.028	-1000
HIF-1-alpha transcription factor network	0.1250	10	777	76	-0.099	0.086	1000	-1000	-0.035	-1000
IL4-mediated signaling events	0.1250	10	967	91	-0.17	0.16	1000	-1000	-0.11	-1000
LPA receptor mediated events	0.1250	10	1071	102	-0.054	0.01	1000	-1000	-0.026	-1000
LPA4-mediated signaling events	0.1125	9	114	12	-0.004	0.013	1000	-1000	-0.003	-1000
Signaling events mediated by the Hedgehog family	0.1125	9	476	52	-0.014	0.037	1000	-1000	-0.008	-1000
Noncanonical Wnt signaling pathway	0.1125	9	251	26	-0.019	0.01	1000	-1000	-0.013	-1000
Signaling mediated by p38-alpha and p38-beta	0.1125	9	431	44	-0.05	0.01	1000	-1000	-0.011	-1000
FOXM1 transcription factor network	0.1125	9	459	51	-0.23	0.011	1000	-1000	-0.061	-1000
Thromboxane A2 receptor signaling	0.1000	8	865	105	-0.049	0.064	1000	-1000	-0.031	-1000
S1P1 pathway	0.1000	8	307	36	-0.069	0.01	1000	-1000	-0.012	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.1000	8	363	45	-0.053	0.016	1000	-1000	-0.022	-1000
Coregulation of Androgen receptor activity	0.0875	7	592	76	-0.037	0.034	1000	-1000	-0.012	-1000
Osteopontin-mediated events	0.0875	7	284	38	-0.025	0.028	1000	-1000	-0.013	-1000
Ephrin A reverse signaling	0.0875	7	52	7	-0.01	0.01	1000	-1000	-0.002	-1000
Ephrin B reverse signaling	0.0875	7	365	48	-0.1	0.013	1000	-1000	-0.012	-1000
IL27-mediated signaling events	0.0875	7	375	51	-0.062	0.034	1000	-1000	-0.016	-1000
BCR signaling pathway	0.0875	7	707	99	-0.063	0.025	1000	-1000	-0.017	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0875	7	579	78	-0.099	0.017	1000	-1000	-0.028	-1000
ErbB2/ErbB3 signaling events	0.0750	6	414	65	-0.019	0.039	1000	-1000	-0.019	-1000
Caspase cascade in apoptosis	0.0750	6	491	74	-0.014	0.06	1000	-1000	-0.014	-1000
Regulation of nuclear SMAD2/3 signaling	0.0750	6	938	136	-0.084	0.025	1000	-1000	-0.017	-1000
JNK signaling in the CD4+ TCR pathway	0.0750	6	116	17	-0.035	0.01	1000	-1000	-0.011	-1000
Calcium signaling in the CD4+ TCR pathway	0.0750	6	186	31	-0.036	0.099	1000	-1000	-0.025	-1000
Plasma membrane estrogen receptor signaling	0.0750	6	549	86	-0.086	0.082	1000	-1000	-0.014	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0750	6	592	88	-0.084	0.01	1000	-1000	-0.047	-1000
Ras signaling in the CD4+ TCR pathway	0.0750	6	108	17	-0.01	0.017	1000	-1000	-0.013	-1000
Syndecan-2-mediated signaling events	0.0625	5	405	69	-0.012	0.025	1000	-1000	-0.004	-1000
p75(NTR)-mediated signaling	0.0625	5	706	125	-0.03	0.031	1000	-1000	-0.023	-1000
FOXA2 and FOXA3 transcription factor networks	0.0625	5	253	46	-0.001	0.1	1000	-1000	-0.026	-1000
IFN-gamma pathway	0.0625	5	357	68	-0.026	0.038	1000	-1000	-0.024	-1000
Reelin signaling pathway	0.0625	5	294	56	-0.023	0.025	1000	-1000	-0.012	-1000
EPHB forward signaling	0.0625	5	481	85	-0.027	0.024	1000	-1000	-0.02	-1000
E-cadherin signaling in the nascent adherens junction	0.0625	5	385	76	-0.037	0.017	1000	-1000	-0.022	-1000
Syndecan-4-mediated signaling events	0.0625	5	379	67	-0.032	0.01	1000	-1000	-0.012	-1000
Visual signal transduction: Rods	0.0625	5	282	52	-0.028	0.029	1000	-1000	-0.008	-1000
Aurora B signaling	0.0625	5	348	67	-0.084	0.012	1000	-1000	-0.013	-1000
Cellular roles of Anthrax toxin	0.0500	4	169	39	-0.022	0.01	1000	-1000	-0.01	-1000
BMP receptor signaling	0.0500	4	336	81	-0.06	0.019	1000	-1000	-0.015	-1000
Nectin adhesion pathway	0.0500	4	257	63	-0.03	0.017	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class III	0.0500	4	166	40	-0.04	0.039	1000	-1000	-0.011	-1000
TRAIL signaling pathway	0.0500	4	199	48	-0.022	0.021	1000	-1000	-0.016	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0500	4	220	52	-0.027	0.027	1000	-1000	-0.011	-1000
IL2 signaling events mediated by PI3K	0.0500	4	238	58	-0.045	0.028	1000	-1000	-0.025	-1000
Glypican 2 network	0.0500	4	18	4	-0.003	-0.003	1000	-1000	0.007	-1000
IL2 signaling events mediated by STAT5	0.0500	4	95	22	-0.12	0.011	1000	-1000	-0.016	-1000
TCGA08_retinoblastoma	0.0500	4	33	8	-0.003	0.012	1000	-1000	-0.002	-1000
Regulation of Androgen receptor activity	0.0500	4	329	70	-0.021	0.023	1000	-1000	-0.024	-1000
BARD1 signaling events	0.0375	3	175	57	-0.032	0.021	1000	-1000	-0.012	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0375	3	215	54	-0.022	0.016	1000	-1000	-0.018	-1000
a4b1 and a4b7 Integrin signaling	0.0375	3	15	5	-0.003	0.01	1000	-1000	0.006	-1000
Fc-epsilon receptor I signaling in mast cells	0.0375	3	311	97	-0.019	0.025	1000	-1000	-0.022	-1000
PLK1 signaling events	0.0375	3	293	85	-0.068	0.015	1000	-1000	-0.016	-1000
amb2 Integrin signaling	0.0375	3	308	82	-0.051	0.026	1000	-1000	-0.012	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0375	3	126	37	-0.013	0.021	1000	-1000	-0.011	-1000
IL1-mediated signaling events	0.0375	3	233	62	-0.019	0.021	1000	-1000	-0.017	-1000
HIF-2-alpha transcription factor network	0.0375	3	154	43	-0.1	0.11	1000	-1000	-0.031	-1000
FAS signaling pathway (CD95)	0.0375	3	163	47	-0.01	0.033	1000	-1000	-0.013	-1000
Atypical NF-kappaB pathway	0.0375	3	107	31	-0.012	0.012	1000	-1000	-0.007	-1000
Integrins in angiogenesis	0.0375	3	333	84	-0.077	0.025	1000	-1000	-0.016	-1000
Effects of Botulinum toxin	0.0375	3	101	26	-0.003	0.014	1000	-1000	-0.002	-1000
Nongenotropic Androgen signaling	0.0375	3	200	52	-0.036	0.018	1000	-1000	-0.013	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0375	3	277	74	-0.058	0.026	1000	-1000	-0.029	-1000
IGF1 pathway	0.0375	3	180	57	-0.017	0.022	1000	-1000	-0.016	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0375	3	442	120	-0.033	0.031	1000	-1000	-0.021	-1000
E-cadherin signaling in keratinocytes	0.0375	3	166	43	-0.021	0.011	1000	-1000	-0.009	-1000
E-cadherin signaling events	0.0375	3	19	5	-0.002	0.01	1000	-1000	0.006	-1000
Visual signal transduction: Cones	0.0250	2	79	38	-0.012	0.016	1000	-1000	-0.004	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0250	2	251	85	-0.047	0.011	1000	-1000	-0.013	-1000
Hedgehog signaling events mediated by Gli proteins	0.0250	2	169	65	-0.014	0.02	1000	-1000	-0.023	-1000
Aurora A signaling	0.0250	2	133	60	-0.024	0.022	1000	-1000	-0.004	-1000
Glypican 1 network	0.0250	2	100	48	-0.01	0.018	1000	-1000	-0.008	-1000
ceramide signaling pathway	0.0250	2	116	49	-0.006	0.015	1000	-1000	-0.009	-1000
Paxillin-dependent events mediated by a4b1	0.0250	2	93	36	-0.009	0.021	1000	-1000	-0.012	-1000
Wnt signaling	0.0250	2	14	7	-0.019	0.01	1000	-1000	-0.009	-1000
IL6-mediated signaling events	0.0250	2	195	75	-0.04	0.031	1000	-1000	-0.015	-1000
Rapid glucocorticoid signaling	0.0250	2	43	20	-0.009	0.011	1000	-1000	-0.002	-1000
S1P4 pathway	0.0250	2	69	25	-0.009	0.015	1000	-1000	-0.004	-1000
p38 MAPK signaling pathway	0.0250	2	96	44	-0.03	0.02	1000	-1000	-0.011	-1000
PLK2 and PLK4 events	0.0125	1	4	3	-0.005	0.01	1000	-1000	-0.004	-1000
Arf6 signaling events	0.0125	1	104	62	-0.004	0.024	1000	-1000	-0.015	-1000
Presenilin action in Notch and Wnt signaling	0.0125	1	62	61	-0.007	0.031	1000	-1000	-0.021	-1000
Aurora C signaling	0.0125	1	10	7	-0.001	0.009	1000	-1000	-0.005	-1000
Insulin-mediated glucose transport	0.0125	1	51	32	-0.012	0.018	1000	-1000	-0.009	-1000
mTOR signaling pathway	0.0125	1	53	53	-0.056	0.015	1000	-1000	-0.015	-1000
S1P5 pathway	0.0125	1	25	17	-0.003	0.012	1000	-1000	-0.001	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0125	1	89	83	-0.009	0.018	1000	-1000	-0.01	-1000
FoxO family signaling	0.0125	1	76	64	-0.059	0.014	1000	-1000	-0.01	-1000
Signaling mediated by p38-gamma and p38-delta	0.0125	1	20	15	-0.013	0.01	1000	-1000	-0.004	-1000
Canonical Wnt signaling pathway	0.0125	1	62	51	-0.012	0.023	1000	-1000	-0.017	-1000
Regulation of p38-alpha and p38-beta	0.0125	1	64	54	-0.029	0.027	1000	-1000	-0.023	-1000
TCGA08_rtk_signaling	0.0125	1	30	26	-0.014	0.032	1000	-1000	0.003	-1000
Class I PI3K signaling events	0.0125	1	112	73	-0.047	0.041	1000	-1000	-0.013	-1000
Regulation of Telomerase	0.0125	1	111	102	-0.01	0.027	1000	-1000	-0.033	-1000
Insulin Pathway	0.0125	1	87	74	-0.083	0.029	1000	-1000	-0.018	-1000
VEGFR1 specific signals	0.0125	1	58	56	-0.005	0.019	1000	-1000	-0.01	-1000
S1P3 pathway	0.0125	1	82	42	-0.007	0.017	1000	-1000	-0.009	-1000
Signaling events mediated by PRL	0.0125	1	57	34	-0.027	0.016	1000	-1000	-0.015	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	1	23	0.001	0.024	1000	-1000	-0.009	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0000	0	28	34	-0.008	0.017	1000	-1000	-0.009	-1000
Canonical NF-kappaB pathway	0.0000	0	8	39	-0.009	0.024	1000	-1000	-0.017	-1000
Signaling events mediated by HDAC Class II	0.0000	0	54	75	-0.011	0.029	1000	-1000	-0.01	-1000
ErbB4 signaling events	0.0000	0	56	69	-0.007	0.027	1000	-1000	-0.019	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0000	0	23	28	-0.005	0.016	1000	-1000	-0.006	-1000
Circadian rhythm pathway	0.0000	0	9	22	-0.009	0.013	1000	-1000	-0.016	-1000
Arf6 downstream pathway	0.0000	0	30	43	-0.02	0.023	1000	-1000	-0.013	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	9	68	-0.012	0.021	1000	-1000	-0.013	-1000
Signaling events mediated by HDAC Class I	0.0000	0	59	104	-0.029	0.027	1000	-1000	-0.011	-1000
TCGA08_p53	0.0000	0	3	7	-0.004	0.01	1000	-1000	-0.005	-1000
Syndecan-3-mediated signaling events	0.0000	0	26	35	-0.035	0.031	1000	-1000	-0.008	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0000	0	123	125	-0.02	0.022	1000	-1000	-0.023	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	4	27	-0.008	0.027	1000	-1000	-0.012	-1000
Arf6 trafficking events	0.0000	0	12	71	-0.019	0.02	1000	-1000	-0.011	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0000	0	25	33	-0.006	0.026	1000	-1000	-0.01	-1000
PDGFR-beta signaling pathway	0.0000	0	82	97	-0.073	0.028	1000	-1000	-0.019	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.008	0.008	1000	-1000	-0.008	-1000
Arf1 pathway	0.0000	0	8	54	-0.005	0.016	1000	-1000	-0.009	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.031	1000	-1000	0	-1000
Total	NA	516	35419	6873	-5.2	3.5	125000	-125000	-2	-125000

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.014	0.26	0.52	13	-0.26	16	29
TBX21	-0.086	0.85	1.3	15	-1	26	41
B2M	0.002	0.026	0.061	5	-0.043	16	21
TYK2	0.037	0.1	0.22	17	-0.058	2	19
IL12RB1	0.041	0.11	0.25	15	-0.058	2	17
GADD45B	-0.049	0.63	1	15	-0.79	20	35
IL12RB2	0.032	0.1	0.25	12	-10000	0	12
GADD45G	-0.11	0.74	1.1	15	-0.96	24	39
natural killer cell activation	0.047	0.12	0.25	18	-0.057	1	19
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.009	0.04	0.097	11	-10000	0	11
IL2RA	0.008	0.004	-10000	0	-10000	0	0
IFNG	0.004	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.2	0.48	0.68	7	-0.76	27	34
HLA-DRB5	0.007	0.012	0.05	2	-0.025	5	7
FASLG	-0.084	0.85	1.4	14	-1	25	39
NF kappa B2 p52/RelB	-0.34	0.44	-10000	0	-0.85	30	30
CD4	0.009	0.011	0.05	2	-0.023	6	8
SOCS1	0.01	0.001	-10000	0	-10000	0	0
EntrezGene:6955	0.001	0.031	0.055	15	-0.038	18	33
CD3D	0	0.022	0.054	4	-0.041	12	16
CD3E	0.002	0.02	0.051	4	-0.043	9	13
CD3G	-0.002	0.025	0.057	5	-0.039	19	24
IL12Rbeta2/JAK2	0.012	0.16	0.33	12	-0.15	17	29
CCL3	-0.087	0.86	1.3	15	-1	25	40
CCL4	-0.082	0.9	1.4	15	-1.1	24	39
HLA-A	0.009	0.033	0.067	13	-0.042	17	30
IL18/IL18R	0.047	0.18	0.41	13	-0.2	1	14
NOS2	-0.027	0.73	1.1	17	-0.88	20	37
IL12/IL12R/TYK2/JAK2/SPHK2	0.016	0.26	0.52	13	-0.26	16	29
IL1R1	-0.14	0.79	1.1	15	-1	26	41
IL4	-0.045	0.12	-10000	0	-0.25	18	18
JAK2	0.038	0.1	0.22	17	-0.058	2	19
EntrezGene:6957	0	0.029	0.05	15	-0.039	17	32
TCR/CD3/MHC I/CD8	-0.16	0.56	0.66	13	-0.82	26	39
RAB7A	-0.044	0.6	0.94	15	-0.74	19	34
lysosomal transport	-0.032	0.58	0.94	15	-0.7	18	33
FOS	-0.034	0.6	0.91	16	-0.71	22	38
STAT4 (dimer)	-0.11	0.65	0.93	15	-0.82	27	42
STAT5A (dimer)	-0.34	0.44	-10000	0	-0.85	30	30
GZMA	-0.15	0.87	1.2	15	-1.1	28	43
GZMB	-0.089	0.82	1.2	16	-1	26	42
HLX	0.01	0.001	-10000	0	-10000	0	0
LCK	-0.073	0.88	1.3	16	-1	26	42
TCR/CD3/MHC II/CD4	-0.1	0.2	0.26	2	-0.39	21	23
IL2/IL2R	-0.012	0.056	-10000	0	-0.12	16	16
MAPK14	-0.078	0.69	1	16	-0.88	22	38
CCR5	-0.065	0.82	1.3	15	-1	21	36
IL1B	0.038	0.11	0.23	16	-0.057	1	17
STAT6	0.057	0.34	0.71	14	-10000	0	14
STAT4	0.008	0.004	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.009	0.003	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.049	0.12	0.27	17	-0.057	1	18
CD8A	-0.001	0.02	0.052	2	-0.044	12	14
CD8B	0	0.019	0.052	2	-0.042	10	12
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.014	0.26	0.26	16	-0.52	13	29
IL2RB	0.008	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.072	0.64	0.94	16	-0.75	27	43
IL2RG	0.007	0.005	-10000	0	-10000	0	0
IL12	0.058	0.15	0.36	15	-10000	0	15
STAT5A	0.01	0	-10000	0	-10000	0	0
CD247	-0.001	0.024	0.051	4	-0.042	17	21
IL2	0	0.002	-10000	0	-10000	0	0
SPHK2	0.01	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.035	0.1	0.23	16	-0.058	2	18
IL12/IL12R/TYK2/JAK2	-0.066	0.97	1.6	15	-1.1	26	41
MAP2K3	-0.07	0.69	1	16	-0.87	22	38
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	-0.079	0.7	1	16	-0.86	24	40
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.013	0.055	2	-0.025	6	8
IL18RAP	0.015	0.05	0.11	14	-10000	0	14
IL12Rbeta1/TYK2	0.003	0.12	0.27	8	-0.16	9	17
EOMES	-0.23	0.44	0.37	2	-0.96	20	22
STAT1 (dimer)	-0.19	0.47	0.69	7	-0.76	25	32
T cell proliferation	-0.007	0.56	0.88	17	-0.6	25	42
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.015	0.054	0.12	14	-10000	0	14
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.26	0.29	-10000	0	-0.62	29	29
ATF2	-0.079	0.63	0.92	16	-0.8	23	39

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.12	0.22	0.17	3	-0.4	25	28
FYN	-0.016	0.45	0.62	18	-0.48	26	44
LAT/GRAP2/SLP76	-0.13	0.22	0.13	1	-0.4	27	28
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.032	0.41	0.68	17	-0.35	25	42
B2M	0.006	0.019	0.086	3	-0.016	13	16
IKBKG	-0.036	0.054	0.056	4	-0.11	25	29
MAP3K8	0.01	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.017	-10000	0	-0.037	27	27
integrin-mediated signaling pathway	0.01	0.018	-10000	0	-0.1	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.001	0.49	0.74	17	-0.48	26	43
TRPV6	0.016	0.087	0.56	2	-10000	0	2
CD28	0.009	0.013	0.044	7	-0.01	13	20
SHC1	-0.02	0.44	0.63	17	-0.5	25	42
receptor internalization	-0.11	0.3	0.49	5	-0.45	26	31
PRF1	-0.018	0.53	0.96	11	-0.82	14	25
KRAS	0.01	0.001	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.03	0.35	0.6	16	-0.28	26	42
LAT	-0.043	0.42	0.6	15	-0.49	26	41
EntrezGene:6955	0.008	0.025	0.068	11	-0.017	5	16
CD3D	0.004	0.008	-10000	0	-0.016	5	5
CD3E	0.004	0.008	-10000	0	-0.015	3	3
CD3G	0.005	0.012	0.081	1	-0.014	6	7
RASGRP2	-0.015	0.051	0.071	4	-0.13	9	13
RASGRP1	0.044	0.46	0.82	16	-0.34	29	45
HLA-A	0.015	0.036	0.1	11	-0.016	18	29
RASSF5	0.009	0.003	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.01	0.018	-10000	0	-0.1	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.085	0.29	0.57	16	-0.1	23	39
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.066	0.086	-10000	0	-0.18	26	26
PRKCA	-0.069	0.11	0.089	3	-0.2	27	30
GRAP2	0.008	0.004	-10000	0	-10000	0	0
mol:IP3	-0.11	0.16	-10000	0	-0.31	28	28
EntrezGene:6957	0.009	0.028	0.077	11	-0.017	4	15
TCR/CD3/MHC I/CD8	-0.018	0.39	0.78	11	-0.46	21	32
ORAI1	-0.017	0.07	-10000	0	-0.44	2	2
CSK	-0.068	0.38	0.51	14	-0.5	25	39
B7 family/CD28	-0.12	0.26	0.73	2	-0.42	24	26
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.18	0.3	-10000	0	-0.56	25	25
PTPN6	-0.084	0.35	0.45	12	-0.47	26	38
VAV1	-0.041	0.43	0.6	16	-0.49	26	42
Monovalent TCR/CD3	-0.068	0.14	0.43	1	-0.25	24	25
CBL	0.01	0	-10000	0	-10000	0	0
LCK	-0.028	0.47	0.64	18	-0.52	27	45
PAG1	-0.07	0.38	0.51	14	-0.5	25	39
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.17	0.28	-10000	0	-0.54	24	24
CD80	0.007	0.011	0.039	6	-0.006	15	21
CD86	0.009	0.012	0.041	6	-0.01	12	18
PDK1/CARD11/BCL10/MALT1	-0.077	0.1	-10000	0	-0.22	25	25
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	-0.06	0.3	0.67	7	-0.36	24	31
CD8A	0.004	0.007	-10000	0	-0.014	3	3
CD8B	0.002	0.008	-10000	0	-0.018	3	3
PTPRC	0.004	0.009	0.023	3	-0.01	16	19
PDK1/PKC theta	0.017	0.46	0.73	17	-0.43	25	42
CSK/PAG1	-0.088	0.34	0.44	12	-0.5	24	36
SOS1	0.01	0.001	-10000	0	-10000	0	0
peptide-MHC class I	0.008	0.035	0.14	3	-0.13	1	4
GRAP2/SLP76	-0.15	0.25	0.15	2	-0.47	26	28
STIM1	-0.003	0.016	-10000	0	-0.13	1	1
RAS family/GTP	0.08	0.31	0.57	17	-0.14	23	40
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.26	-10000	0	-0.46	27	27
mol:DAG	-0.1	0.14	-10000	0	-0.28	28	28
RAP1A/GDP	0.054	0.18	0.34	16	-0.047	23	39
PLCG1	0.009	0.004	-10000	0	-0.006	4	4
CD247	0.005	0.009	-10000	0	-0.017	6	6
cytotoxic T cell degranulation	-0.009	0.51	0.96	11	-0.77	14	25
RAP1A/GTP	-0.008	0.017	-10000	0	-0.058	7	7
mol:PI-3-4-5-P3	0.022	0.45	0.72	17	-0.41	25	42
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.14	0.21	-10000	0	-0.39	28	28
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.007	0.005	-10000	0	-0.001	3	3
GRB2/SOS1	0.014	0.015	-10000	0	-0.12	1	1
LAT/GRAP2/SLP76/VAV1	-0.14	0.21	-10000	0	-0.39	28	28
MALT1	0.01	0.001	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.038	0.083	-10000	0	-0.17	20	20
CARD11	0.006	0.005	-10000	0	-10000	0	0
PRKCB	-0.068	0.11	0.089	3	-0.2	27	30
PRKCE	-0.069	0.11	0.089	3	-0.21	27	30
PRKCQ	0.003	0.49	0.75	17	-0.47	26	43
LCP2	0.009	0.003	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.045	0.39	0.66	17	-0.3	25	42
IKK complex	0.085	0.28	0.52	17	-0.093	17	34
RAS family/GDP	-0.011	0.013	-10000	0	-0.029	25	25
MAP3K14	0.053	0.33	0.58	17	-0.22	26	43
PDPK1	0.037	0.41	0.68	17	-0.33	25	42
TCR/CD3/MHC I/CD8/Fyn	-0.19	0.35	0.19	1	-0.66	23	24

×

IL23-mediated signaling events

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
CCL2	0.057	0.66	0.98	19	-0.98	11	30
IL23A	0.05	0.68	1	17	-1.1	11	28
NF kappa B1 p50/RelA/I kappa B alpha	-0.22	0.38	-10000	0	-0.99	12	12
positive regulation of T cell mediated cytotoxicity	0.093	0.8	1.2	19	-1.1	11	30
ITGA3	0.033	0.64	0.92	18	-0.98	12	30
IL17F	0.04	0.46	0.69	19	-0.65	11	30
IL12B	0.074	0.15	0.31	20	-10000	0	20
STAT1 (dimer)	-0.11	0.54	0.76	10	-1	12	22
CD4	0.042	0.66	0.94	19	-1	11	30
IL23	-0.012	0.59	0.88	11	-0.98	12	23
IL23R	0.14	0.33	0.7	17	-10000	0	17
IL1B	0.055	0.7	1.1	17	-1.1	11	28
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.044	0.66	1	16	-0.96	12	28
TYK2	0.042	0.087	0.18	19	-10000	0	19
STAT4	0.008	0.004	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
IL18RAP	0.004	0.016	0.054	5	-0.02	4	9
IL12RB1	0.043	0.11	0.26	14	-10000	0	14
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.026	0.12	0.28	12	-0.14	8	20
IL23R/JAK2	0.13	0.31	0.63	19	-10000	0	19
positive regulation of chronic inflammatory response	0.093	0.8	1.2	19	-1.1	11	30
natural killer cell activation	-0.013	0.033	-10000	0	-0.064	19	19
JAK2	0.076	0.14	0.3	20	-10000	0	20
PIK3R1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.009	0.019	0.037	16	-10000	0	16
RELA	0.009	0.019	0.04	11	-10000	0	11
positive regulation of dendritic cell antigen processing and presentation	-0.004	0.57	0.82	15	-0.93	12	27
ALOX12B	0.056	0.65	0.96	19	-0.96	11	30
CXCL1	0.058	0.66	0.98	19	-0.96	11	30
T cell proliferation	0.093	0.8	1.2	19	-1.1	11	30
NFKBIA	0.009	0.019	0.04	11	-10000	0	11
IL17A	0.061	0.41	0.65	19	-0.55	7	26
PI3K	-0.2	0.42	-10000	0	-0.97	13	13
IFNG	0.025	0.091	0.24	8	-10000	0	8
STAT3 (dimer)	-0.22	0.37	-10000	0	-0.93	13	13
IL18R1	0.007	0.017	0.056	6	-0.02	4	10
IL23/IL23R/JAK2/TYK2/SOCS3	0.098	0.52	0.86	20	-0.65	7	27
IL18/IL18R	-0.003	0.064	0.22	3	-0.11	12	15
macrophage activation	-0.011	0.018	0.051	1	-0.042	12	13
TNF	0.053	0.7	1.1	17	-1	12	29
STAT3/STAT4	-0.2	0.42	-10000	0	-0.97	13	13
STAT4 (dimer)	-0.083	0.56	0.75	12	-1	12	24
IL18	0.005	0.013	0.049	2	-0.02	4	6
IL19	0.049	0.64	0.97	17	-1.1	8	25
STAT5A (dimer)	-0.001	0.63	0.82	19	-1	12	31
STAT1	0.009	0.003	-10000	0	-10000	0	0
SOCS3	0.01	0.002	-10000	0	-10000	0	0
CXCL9	0	0.83	1.1	19	-1.2	17	36
MPO	0.006	0.7	0.95	19	-1	15	34
positive regulation of humoral immune response	0.093	0.8	1.2	19	-1.1	11	30
IL23/IL23R/JAK2/TYK2	0.081	0.82	1.2	19	-1.2	11	30
IL6	0.049	0.65	0.98	17	-0.98	11	28
STAT5A	0.01	0	-10000	0	-10000	0	0
IL2	0.012	0.05	0.16	8	-0.046	4	12
positive regulation of tyrosine phosphorylation of STAT protein	-0.013	0.033	-10000	0	-0.064	19	19
CD3E	0.007	0.83	1.1	20	-1.2	18	38
keratinocyte proliferation	0.093	0.8	1.2	19	-1.1	11	30
NOS2	0.038	0.63	0.93	18	-0.96	11	29

×

Endothelins

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
AKT1	0.023	0.17	0.25	23	-0.25	7	30
PTK2B	0.01	0.003	0.019	2	-0.008	2	4
mol:Ca2+	0.006	0.27	0.61	5	-0.8	4	9
EDN1	0.008	0.11	0.15	21	-0.16	17	38
EDN3	0.005	0.005	-10000	0	-10000	0	0
EDN2	0.005	0.005	-10000	0	-10000	0	0
HRAS/GDP	0	0.17	0.28	9	-0.3	10	19
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.007	0.14	0.25	9	-0.24	10	19
ADCY4	0.014	0.14	0.2	20	-0.21	11	31
ADCY5	0.017	0.14	0.2	21	-0.21	10	31
ADCY6	0.02	0.14	0.2	22	-0.2	10	32
ADCY7	0.019	0.14	0.2	22	-0.21	10	32
ADCY1	-0.018	0.12	0.18	11	-0.22	13	24
ADCY2	-0.013	0.12	0.19	11	-0.21	13	24
ADCY3	0.02	0.14	0.2	22	-0.21	9	31
ADCY8	0.004	0.13	0.2	16	-0.21	9	25
ADCY9	0.02	0.14	0.2	22	-0.21	9	31
arachidonic acid secretion	-0.005	0.22	0.44	6	-0.42	9	15
ETB receptor/Endothelin-1/Gq/GTP	0.007	0.11	0.21	9	-0.18	9	18
GNAO1	0.009	0.003	-10000	0	-10000	0	0
HRAS	0.01	0.004	0.022	2	-0.007	3	5
ETA receptor/Endothelin-1/G12/GTP	-0.03	0.1	0.24	4	-0.17	20	24
ETA receptor/Endothelin-1/Gs/GTP	-0.032	0.1	0.23	4	-0.17	19	23
mol:GTP	0.003	0.012	0.037	7	-0.02	2	9
COL3A1	0.013	0.18	0.26	21	-0.3	7	28
EDNRB	0.019	0.052	0.14	10	-0.078	5	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.052	0.17	0.27	7	-0.32	17	24
CYSLTR1	0.013	0.18	0.25	22	-0.32	7	29
SLC9A1	-0.025	0.078	0.17	5	-0.16	10	15
mol:GDP	0	0.18	0.29	9	-0.31	10	19
SLC9A3	-0.066	0.25	0.41	6	-0.43	17	23
RAF1	0.003	0.18	0.38	5	-0.3	11	16
JUN	0.009	0.24	0.54	5	-0.78	3	8
JAK2	0.025	0.17	0.25	23	-0.25	7	30
mol:IP3	-0.002	0.15	0.27	9	-0.25	10	19
ETA receptor/Endothelin-1	-0.044	0.13	0.27	4	-0.23	20	24
PLCB1	0.007	0.007	0.029	1	-0.009	6	7
PLCB2	0.009	0.01	0.028	6	-0.014	8	14
ETA receptor/Endothelin-3	-0.029	0.065	0.1	2	-0.13	20	22
FOS	-0.028	0.26	0.53	3	-0.79	6	9
Gai/GDP	0.001	0.095	-10000	0	-0.43	3	3
CRK	0.01	0.003	0.019	2	-0.008	2	4
mol:Ca ++	0.015	0.22	0.34	14	-0.3	14	28
BCAR1	0.01	0.001	-10000	0	-10000	0	0
PRKCB1	0.007	0.15	0.27	9	-0.26	9	18
GNAQ	0.012	0.016	0.055	7	-0.022	5	12
GNAZ	0.01	0.002	-10000	0	-10000	0	0
GNAL	0.008	0.004	-10000	0	-10000	0	0
Gs family/GDP	-0.032	0.14	0.19	7	-0.3	10	17
ETA receptor/Endothelin-1/Gq/GTP	0.018	0.14	0.32	7	-0.21	7	14
MAPK14	-0.004	0.11	0.21	7	-0.2	10	17
TRPC6	0.003	0.28	0.61	5	-0.87	4	9
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.01	0.002	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.002	0.12	0.22	8	-0.21	10	18
ETB receptor/Endothelin-2	-0.006	0.051	0.099	4	-0.11	12	16
ETB receptor/Endothelin-3	-0.034	0.084	0.11	4	-0.15	23	27
ETB receptor/Endothelin-1	-0.026	0.098	0.23	5	-0.17	15	20
MAPK3	-0.021	0.24	0.46	4	-0.67	6	10
MAPK1	-0.021	0.24	0.46	4	-0.67	6	10
Rac1/GDP	0.002	0.17	0.28	9	-0.3	10	19
cAMP biosynthetic process	0.031	0.22	0.29	22	-0.26	17	39
MAPK8	0.003	0.26	0.54	5	-0.57	7	12
SRC	0.01	0.003	0.017	1	-0.009	2	3
ETB receptor/Endothelin-1/Gi/GTP	-0.003	0.088	0.16	7	-0.15	13	20
p130Cas/CRK/Src/PYK2	0.015	0.2	0.42	7	-0.33	8	15
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.002	0.17	0.28	9	-0.3	10	19
COL1A2	-0.028	0.19	0.24	15	-0.36	11	26
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.008	0.054	0.12	6	-0.098	14	20
mol:DAG	-0.002	0.15	0.27	9	-0.25	10	19
MAP2K2	-0.009	0.2	0.4	5	-0.38	10	15
MAP2K1	-0.009	0.2	0.4	5	-0.37	11	16
EDNRA	0.016	0.1	0.15	23	-0.14	16	39
positive regulation of muscle contraction	0.016	0.14	0.21	22	-0.21	8	30
Gq family/GDP	-0.043	0.1	0.26	1	-0.25	10	11
HRAS/GTP	0.012	0.16	0.29	9	-0.29	9	18
PRKCH	0.008	0.15	0.26	9	-0.26	9	18
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	0.006	0.15	0.26	9	-0.26	9	18
PRKCB	0.013	0.16	0.26	13	-0.27	9	22
PRKCE	0.004	0.15	0.26	9	-0.26	9	18
PRKCD	0.006	0.15	0.26	9	-0.26	9	18
PRKCG	0.011	0.15	0.27	10	-0.26	9	19
regulation of vascular smooth muscle contraction	-0.04	0.3	0.54	3	-0.93	6	9
PRKCQ	0.007	0.16	0.26	10	-0.27	10	20
PLA2G4A	-0.011	0.24	0.45	6	-0.46	9	15
GNA14	0.011	0.016	0.055	7	-0.026	3	10
GNA15	0.011	0.013	0.045	7	-0.019	4	11
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.011	0.013	0.045	7	-0.019	4	11
Rac1/GTP	-0.03	0.1	0.24	4	-0.17	20	24
MMP1	0.002	0.15	0.42	1	-0.53	5	6

×

Syndecan-1-mediated signaling events

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
TGFB1	0.01	0.002	-10000	0	-10000	0	0
CCL5	0.007	0.005	-10000	0	-10000	0	0
SDCBP	0.01	0	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.011	0.14	0.23	9	-0.19	23	32
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	-0.011	0.14	0.21	9	-0.19	23	32
Syndecan-1/Syntenin	-0.01	0.13	0.21	9	-0.18	23	32
MAPK3	-0.011	0.12	0.19	9	-0.18	19	28
HGF/MET	-0.001	0.044	-10000	0	-0.12	9	9
TGFB1/TGF beta receptor Type II	0.01	0.002	-10000	0	-10000	0	0
BSG	0.01	0	-10000	0	-10000	0	0
keratinocyte migration	-0.011	0.13	0.2	9	-0.18	23	32
Syndecan-1/RANTES	-0.032	0.14	0.2	5	-0.2	23	28
Syndecan-1/CD147	-0.006	0.13	0.2	9	-0.18	23	32
Syndecan-1/Syntenin/PIP2	-0.022	0.12	0.16	5	-0.18	23	28
LAMA5	0.01	0.001	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.032	0.1	-10000	0	-0.17	23	23
MMP7	0.003	0.005	-10000	0	-10000	0	0
HGF	0.008	0.004	-10000	0	-10000	0	0
Syndecan-1/CASK	-0.037	0.11	-10000	0	-0.18	23	23
Syndecan-1/HGF/MET	-0.023	0.13	0.19	6	-0.19	23	29
regulation of cell adhesion	-0.016	0.12	0.19	9	-0.28	7	16
HPSE	0.007	0.005	-10000	0	-10000	0	0
positive regulation of cell migration	-0.011	0.14	0.23	9	-0.19	23	32
SDC1	-0.018	0.14	0.22	7	-0.19	23	30
Syndecan-1/Collagen	-0.011	0.14	0.23	9	-0.19	23	32
PPIB	0.01	0	-10000	0	-10000	0	0
MET	0.01	0.002	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
MMP9	0.007	0.005	-10000	0	-10000	0	0
MAPK1	-0.011	0.12	0.19	9	-0.2	14	23
homophilic cell adhesion	-0.011	0.14	0.23	9	-0.19	23	32
MMP1	0.006	0.005	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.018	0.049	0.19	5	-0.12	1	6
NFATC2	-0.036	0.27	0.37	10	-0.43	14	24
NFATC3	0.048	0.14	0.26	15	-0.22	4	19
CD40LG	-0.06	0.38	0.58	10	-0.68	14	24
ITCH	-0.005	0.097	0.26	6	-0.3	2	8
CBLB	-0.006	0.077	0.24	5	-10000	0	5
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.13	0.3	0.49	4	-0.64	15	19
JUNB	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.06	-10000	0	-0.18	8	8
T cell anergy	-0.021	0.16	0.41	5	-0.32	8	13
TLE4	-0.02	0.2	0.29	10	-0.36	10	20
Jun/NFAT1-c-4/p21SNFT	-0.091	0.32	0.52	5	-0.66	13	18
AP-1/NFAT1-c-4	-0.092	0.38	0.68	6	-0.75	14	20
IKZF1	0.002	0.22	0.42	10	-0.34	10	20
T-helper 2 cell differentiation	-0.042	0.3	0.53	7	-0.58	7	14
AP-1/NFAT1	-0.037	0.18	0.38	5	-0.3	13	18
CALM1	0.007	0.05	0.13	5	-0.12	8	13
EGR2	0.032	0.48	0.87	13	-0.73	10	23
EGR3	0.003	0.55	0.75	19	-1	10	29
NFAT1/FOXP3	-0.039	0.18	0.36	6	-0.3	13	19
EGR1	0.015	0.031	0.15	4	-10000	0	4
JUN	0.029	0.067	0.14	16	-10000	0	16
EGR4	0.011	0.032	0.15	4	-0.036	1	5
mol:Ca2+	-0.014	0.032	-10000	0	-0.11	8	8
GBP3	-0.04	0.3	0.48	11	-0.45	20	31
FOSL1	0.009	0.003	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.079	0.3	0.43	5	-0.65	12	17
DGKA	-0.018	0.19	0.29	10	-0.34	10	20
CREM	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.099	0.29	0.44	4	-0.63	13	17
CTLA4	-0.026	0.16	0.33	7	-0.26	11	18
NFAT1-c-4 (dimer)/EGR1	-0.093	0.3	0.46	4	-0.7	11	15
NFAT1-c-4 (dimer)/EGR4	-0.082	0.3	0.45	5	-0.65	12	17
FOS	0.028	0.066	0.14	14	-10000	0	14
IFNG	-0.11	0.26	0.66	2	-0.53	13	15
T cell activation	0.013	0.31	0.66	8	-0.6	3	11
MAF	0.01	0.001	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.057	0.4	0.57	9	-0.76	13	22
TNF	-0.048	0.32	0.48	9	-0.66	10	19
FASLG	-0.048	0.64	1	12	-1.1	15	27
TBX21	0.013	0.036	0.24	2	-10000	0	2
BATF3	0.009	0.003	-10000	0	-10000	0	0
PRKCQ	0.011	0.066	0.11	11	-0.15	6	17
PTPN1	-0.016	0.19	0.29	10	-0.32	10	20
NFAT1-c-4/ICER1	-0.08	0.31	0.44	5	-0.66	12	17
GATA3	0.009	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	-0.11	0.26	0.65	2	-0.52	13	15
IL2RA	-0.14	0.29	0.46	2	-0.61	17	19
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.016	0.19	0.29	11	-0.32	10	21
E2F1	0.011	0.002	-10000	0	-10000	0	0
PPARG	0.006	0.005	-10000	0	-10000	0	0
SLC3A2	-0.016	0.19	0.29	10	-0.32	10	20
IRF4	0.01	0.002	-10000	0	-10000	0	0
PTGS2	-0.026	0.44	0.68	14	-0.7	15	29
CSF2	-0.014	0.43	0.68	14	-0.68	14	28
JunB/Fra1/NFAT1-c-4	-0.082	0.3	0.43	5	-0.66	12	17
IL4	-0.042	0.31	0.54	7	-0.6	7	14
IL5	-0.014	0.43	0.68	14	-0.68	14	28
IL2	0.012	0.31	0.66	8	-0.61	3	11
IL3	-0.032	0.047	-10000	0	-10000	0	0
RNF128	-0.032	0.081	-10000	0	-0.3	6	6
NFATC1	0.057	0.4	0.77	13	-0.58	9	22
CDK4	-0.06	0.37	0.46	8	-0.75	12	20
PTPRK	-0.035	0.24	0.3	13	-0.43	14	27
IL8	-0.047	0.41	0.68	11	-0.69	14	25
POU2F1	0.01	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.006	0.019	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.053	0.082	-10000	0	-0.17	24	24
JUN	-0.028	0.085	0.13	1	-0.14	24	25
HRAS	0.01	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.019	0.056	-10000	0	-0.099	25	25
RAP1A	0.01	0	-10000	0	-10000	0	0
FRS2	0.01	0	-10000	0	-10000	0	0
RAP1A/GDP	0.008	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.018	0.054	-10000	0	-0.096	25	25
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.02	0.051	-10000	0	-0.094	25	25
RHOA	0.01	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.015	0.049	-10000	0	-0.086	25	25
GRB7	0.007	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF	-0.018	0.054	-10000	0	-0.096	25	25
MAPKKK cascade	-0.033	0.063	-10000	0	-0.12	26	26
BCAR1	0.01	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.021	0.055	-10000	0	-0.097	25	25
lamellipodium assembly	-0.05	0.08	-10000	0	-0.17	24	24
RET51/GFRalpha1/GDNF/SHC	-0.018	0.054	-10000	0	-0.096	25	25
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.02	0.051	-10000	0	-0.094	25	25
RET9/GFRalpha1/GDNF/Shank3	-0.02	0.051	-10000	0	-0.094	25	25
MAPK3	-0.002	0.082	0.14	15	-0.15	1	16
DOK1	0.01	0	-10000	0	-10000	0	0
DOK6	0.008	0.004	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
neurite development	-0.012	0.077	0.13	13	-0.13	5	18
DOK5	0.008	0.004	-10000	0	-10000	0	0
GFRA1	0.006	0.005	-10000	0	-10000	0	0
MAPK8	-0.032	0.087	0.088	11	-0.15	25	36
HRAS/GTP	-0.031	0.07	-10000	0	-0.13	26	26
tube development	-0.02	0.048	-10000	0	-0.089	25	25
MAPK1	-0.002	0.082	0.14	15	-0.15	1	16
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.073	-10000	0	-0.15	25	25
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
SRC	0.01	0	-10000	0	-10000	0	0
PDLIM7	0.01	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.026	0.061	-10000	0	-0.1	29	29
SHC1	0.01	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.018	0.054	-10000	0	-0.096	25	25
RET51/GFRalpha1/GDNF/Dok5	-0.032	0.069	-10000	0	-0.12	29	29
PRKCA	0.01	0	-10000	0	-10000	0	0
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
CREB1	-0.039	0.1	-10000	0	-0.18	25	25
PIK3R1	0.01	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.042	0.073	-10000	0	-0.15	25	25
RET51/GFRalpha1/GDNF/Grb7	-0.019	0.052	-10000	0	-0.095	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.01	0.002	-10000	0	-10000	0	0
DOK4	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.027	0.096	0.16	4	-0.15	26	30
RET9/GFRalpha1/GDNF/FRS2	-0.02	0.051	-10000	0	-0.094	25	25
SHANK3	0.01	0	-10000	0	-10000	0	0
RASA1	0.01	0.001	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.044	0.073	-10000	0	-0.15	26	26
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.042	0.073	-10000	0	-0.15	25	25
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.045	0.078	-10000	0	-0.15	26	26
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.043	0.074	-10000	0	-0.15	26	26
PI3K	-0.047	0.13	0.2	3	-0.23	24	27
SOS1	0.01	0.001	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.016	0.05	-10000	0	-0.089	25	25
GRB10	0.01	0.001	-10000	0	-10000	0	0
activation of MAPKK activity	-0.038	0.085	-10000	0	-0.16	24	24
RET51/GFRalpha1/GDNF/FRS2	-0.018	0.054	-10000	0	-0.096	25	25
GAB1	0.01	0	-10000	0	-10000	0	0
IRS1	0.01	0.001	-10000	0	-10000	0	0
IRS2	0.01	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.042	0.073	-10000	0	-0.15	25	25
RET51/GFRalpha1/GDNF/PKC alpha	-0.018	0.054	-10000	0	-0.096	25	25
GRB2	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GDNF	0.007	0.005	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.019	0.058	-10000	0	-0.099	25	25
Rac1/GTP	-0.057	0.093	-10000	0	-0.19	24	24
RET9/GFRalpha1/GDNF	-0.026	0.053	-10000	0	-0.1	25	25
GFRalpha1/GDNF	-0.033	0.065	-10000	0	-0.13	25	25

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.01	0.087	0.22	6	-10000	0	6
SMARCC2	0.006	0.028	0.051	8	-0.059	10	18
SMARCC1	0.006	0.028	0.051	8	-0.058	10	18
TBX21	-0.04	0.22	0.39	5	-0.4	15	20
SUMO2	0.019	0.027	0.058	16	-10000	0	16
STAT1 (dimer)	0.02	0.078	0.25	6	-0.18	4	10
FKBP4	0.01	0	-10000	0	-10000	0	0
FKBP5	0.008	0.004	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.02	0.1	0.21	12	-0.14	3	15
PRL	-0.012	0.18	0.43	4	-0.77	2	6
cortisol/GR alpha (dimer)/TIF2	0.061	0.24	0.46	15	-0.38	4	19
RELA	0.02	0.066	0.16	10	-0.14	5	15
FGG	0.057	0.2	0.42	10	-0.39	2	12
GR beta/TIF2	0.026	0.12	0.21	14	-0.2	4	18
IFNG	-0.027	0.22	0.54	5	-0.48	5	10
apoptosis	0.14	0.32	0.56	23	-0.44	1	24
CREB1	0.01	0.001	-10000	0	-10000	0	0
histone acetylation	-0.02	0.21	0.36	10	-0.31	17	27
BGLAP	-0.026	0.12	-10000	0	-0.32	4	4
GR/PKAc	0.041	0.095	0.2	13	-0.13	1	14
NF kappa B1 p50/RelA	0.038	0.11	0.28	10	-0.22	5	15
SMARCD1	0.006	0.028	0.051	8	-0.058	10	18
MDM2	0.032	0.087	0.18	13	-0.13	1	14
GATA3	0.009	0.004	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
CSF2	-0.057	0.13	-10000	0	-0.35	1	1
GSK3B	0.019	0.027	0.058	16	-10000	0	16
NR1I3	0.16	0.3	0.59	16	-10000	0	16
CSN2	0.055	0.18	0.38	9	-0.36	2	11
BRG1/BAF155/BAF170/BAF60A	0.018	0.087	0.18	8	-0.17	10	18
NFATC1	0.011	0.001	-10000	0	-10000	0	0
POU2F1	0.017	0.049	0.17	5	-0.26	1	6
CDKN1A	-0.098	0.32	-10000	0	-1.1	7	7
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.015	0.027	0.05	21	-10000	0	21
SFN	0.007	0.005	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.013	0.089	0.19	9	-0.15	4	13
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.14	0.34	0.68	13	-0.58	4	17
JUN	0.043	0.2	0.5	8	-0.3	4	12
IL4	-0.028	0.12	-10000	0	-0.35	2	2
CDK5R1	0.014	0.018	0.046	10	-10000	0	10
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.004	0.052	0.18	4	-10000	0	4
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.022	0.1	0.21	11	-0.13	3	14
cortisol/GR alpha (monomer)	0.073	0.27	0.53	15	-0.46	2	17
NCOA2	0.009	0.003	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.04	0.083	0.24	9	-0.11	2	11
AP-1/NFAT1-c-4	0.034	0.23	0.57	8	-0.39	4	12
AFP	0.034	0.14	0.42	1	-10000	0	1
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.028	0.2	0.37	7	-0.52	4	11
TP53	-0.026	0.13	-10000	0	-0.44	7	7
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.047	0.3	0.65	6	-0.73	7	13
KRT14	-0.13	0.47	0.59	9	-0.98	15	24
TBP	0.013	0	-10000	0	-10000	0	0
CREBBP	0.016	0.17	0.26	20	-0.22	20	40
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC2	0.01	0	-10000	0	-10000	0	0
AP-1	0.034	0.24	0.57	8	-0.4	4	12
MAPK14	0.02	0.028	0.06	17	-10000	0	17
MAPK10	0.015	0.03	0.07	12	-10000	0	12
MAPK11	0.019	0.027	0.058	16	-10000	0	16
KRT5	-0.011	0.26	0.58	8	-0.43	8	16
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
STAT1	0.02	0.078	0.25	6	-0.18	4	10
CGA	-0.028	0.12	-10000	0	-0.35	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.023	0.19	0.34	8	-0.39	4	12
MAPK3	0.022	0.031	0.061	21	-10000	0	21
MAPK1	0.02	0.028	0.063	15	-10000	0	15
ICAM1	-0.045	0.14	-10000	0	-0.44	2	2
NFKB1	0.02	0.066	0.16	10	-0.14	5	15
MAPK8	0.019	0.16	0.35	8	-0.29	8	16
MAPK9	0.02	0.028	0.061	16	-10000	0	16
cortisol/GR alpha (dimer)	0.13	0.32	0.56	22	-0.44	2	24
BAX	-0.03	0.11	-10000	0	-0.46	2	2
POMC	-0.3	0.62	0.54	8	-1.2	26	34
EP300	0.016	0.17	0.26	20	-0.22	20	40
cortisol/GR alpha (dimer)/p53	0.036	0.23	0.45	13	-0.51	2	15
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.07	0.16	8	-10000	0	8
SGK1	-0.071	0.47	0.47	11	-1.2	10	21
IL13	-0.048	0.17	-10000	0	-0.56	2	2
IL6	-0.04	0.15	0.58	1	-0.44	2	3
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.049	0.16	-10000	0	-0.49	2	2
IL2	-0.045	0.19	0.41	3	-0.48	5	8
CDK5	0.014	0.018	0.036	19	-0.011	6	25
PRKACB	0.01	0	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.067	0.24	0.53	2	-0.66	7	9
CDK5R1/CDK5	0.028	0.035	0.1	9	-10000	0	9
NF kappa B1 p50/RelA/PKAc	0.043	0.088	0.23	10	-0.16	5	15
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.067	0.22	0.43	15	-0.37	2	17
SMARCA4	0.006	0.028	0.051	8	-0.059	10	18
chromatin remodeling	0.018	0.2	0.36	10	-0.38	8	18
NF kappa B1 p50/RelA/Cbp	0.037	0.23	0.36	16	-0.34	11	27
JUN (dimer)	0.043	0.2	0.5	8	-0.3	4	12
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.025	0.16	0.32	1	-0.38	9	10
NR3C1	0.05	0.16	0.34	13	-0.26	2	15
NR4A1	-0.13	0.24	0.15	5	-0.47	26	31
TIF2/SUV420H1	0.005	0.037	-10000	0	-0.12	6	6
MAPKKK cascade	0.14	0.32	0.56	23	-0.44	1	24
cortisol/GR alpha (dimer)/Src-1	0.065	0.23	0.46	15	-0.4	2	17
PBX1	0.016	0.05	0.17	5	-0.26	1	6
POU1F1	0.008	0.049	0.16	5	-0.26	1	6
SELE	-0.029	0.17	0.48	3	-0.44	2	5
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.017	0.21	0.36	10	-0.38	8	18
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.067	0.22	0.43	15	-0.37	2	17
mol:cortisol	0.041	0.16	0.32	13	-0.25	2	15
MMP1	-0.035	0.23	0.5	2	-0.84	5	7

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.047	0.4	0.79	9	-0.66	4	13
HDAC7	0.011	0.015	0.089	2	-10000	0	2
HIF1A/ARNT/Cbp/p300/Src-1	-0.036	0.32	0.64	9	-0.52	5	14
SMAD4	0.01	0	-10000	0	-10000	0	0
ID2	0.047	0.4	0.79	9	-0.66	4	13
AP1	0.002	0.049	0.2	1	-0.12	7	8
ABCG2	0.046	0.4	0.79	9	-0.63	5	14
HIF1A	0.028	0.12	0.32	8	-10000	0	8
TFF3	0.027	0.39	0.78	8	-0.64	5	13
GATA2	0.008	0.026	0.18	1	-0.047	7	8
AKT1	0.031	0.14	0.32	10	-10000	0	10
response to hypoxia	0.018	0.13	0.32	9	-10000	0	9
MCL1	0.047	0.4	0.79	9	-0.66	4	13
NDRG1	0.046	0.4	0.79	9	-0.67	4	13
SERPINE1	0.019	0.39	0.78	7	-0.66	5	12
FECH	0.047	0.4	0.79	9	-0.66	4	13
FURIN	0.047	0.4	0.79	9	-0.66	4	13
NCOA2	0.019	0.037	0.16	5	-10000	0	5
EP300	0.076	0.22	0.54	11	-0.27	1	12
HMOX1	0.027	0.38	0.78	7	-0.66	4	11
BHLHE40	0.047	0.4	0.79	9	-0.66	4	13
BHLHE41	0.042	0.4	0.79	9	-0.66	4	13
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.031	0.14	0.32	10	-0.18	1	11
ENG	0.045	0.14	0.37	7	-10000	0	7
JUN	0.007	0.017	0.1	1	-0.035	7	8
RORA	0.047	0.41	0.8	9	-0.66	4	13
ABCB1	-0.046	0.13	0.46	1	-1	1	2
TFRC	0.047	0.4	0.79	9	-0.66	4	13
CXCR4	0.032	0.4	0.79	8	-0.73	4	12
TF	-0.099	0.3	0.82	3	-0.62	7	10
CITED2	0.047	0.4	0.79	9	-0.66	4	13
HIF1A/ARNT	-0.074	0.33	0.79	4	-0.59	9	13
LDHA	-0.03	0.038	-10000	0	-10000	0	0
ETS1	0.044	0.4	0.79	9	-0.66	4	13
PGK1	0.047	0.4	0.79	9	-0.66	4	13
NOS2	0.046	0.4	0.79	9	-0.66	4	13
ITGB2	0.028	0.39	0.79	8	-0.66	4	12
ALDOA	0.047	0.4	0.79	9	-0.66	4	13
Cbp/p300/CITED2	-0.02	0.38	0.77	8	-0.66	4	12
FOS	0.007	0.017	0.1	1	-0.035	7	8
HK2	0.047	0.4	0.79	9	-0.66	4	13
SP1	0.019	0.039	0.18	4	-0.088	1	5
GCK	0.086	0.34	0.88	6	-1	2	8
HK1	0.047	0.4	0.79	9	-0.66	4	13
NPM1	0.047	0.4	0.79	9	-0.66	4	13
EGLN1	0.047	0.4	0.79	9	-0.66	4	13
CREB1	0.012	0	-10000	0	-10000	0	0
PGM1	0.024	0.4	0.79	8	-0.66	5	13
SMAD3	0.01	0	-10000	0	-10000	0	0
EDN1	-0.022	0.36	0.83	2	-0.98	7	9
IGFBP1	0.006	0.38	0.79	7	-0.65	4	11
VEGFA	0.029	0.34	0.68	9	-0.48	5	14
HIF1A/JAB1	0.017	0.1	0.29	7	-10000	0	7
CP	-0.067	0.33	0.9	2	-0.62	8	10
CXCL12	0.025	0.39	0.8	7	-0.63	5	12
COPS5	0.018	0.028	0.13	5	-10000	0	5
SMAD3/SMAD4	0.015	0	-10000	0	-10000	0	0
BNIP3	0.047	0.4	0.79	9	-0.66	4	13
EGLN3	0.042	0.4	0.79	9	-0.66	4	13
CA9	-0.021	0.35	0.78	4	-0.64	5	9
TERT	0.04	0.4	0.78	9	-0.65	4	13
ENO1	0.047	0.4	0.79	9	-0.66	4	13
PFKL	0.047	0.4	0.79	9	-0.66	4	13
NCOA1	0.014	0.016	0.073	5	-10000	0	5
ADM	0.047	0.4	0.79	9	-0.66	4	13
ARNT	0.028	0.12	0.28	9	-10000	0	9
HNF4A	0.005	0.027	0.1	3	-0.1	2	5
ADFP	-0.002	0.38	0.76	8	-0.65	4	12
SLC2A1	0.043	0.35	0.7	10	-0.49	3	13
LEP	-0.006	0.37	0.78	6	-0.65	4	10
HIF1A/ARNT/Cbp/p300	-0.037	0.33	0.66	9	-0.54	5	14
EPO	0.068	0.38	0.98	7	-0.76	1	8
CREBBP	0.076	0.22	0.54	11	-0.27	1	12
HIF1A/ARNT/Cbp/p300/HDAC7	-0.052	0.29	0.58	8	-0.51	6	14
PFKFB3	0.047	0.4	0.79	9	-0.66	4	13
NT5E	0.008	0.4	0.78	7	-0.65	6	13

×

IL4-mediated signaling events

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
BCL2L1	0.11	0.5	0.88	7	-1.3	4	11
STAT6 (cleaved dimer)	-0.14	0.34	-10000	0	-1	8	8
IGHG1	0.13	0.27	0.58	12	-10000	0	12
IGHG3	0.086	0.46	0.74	7	-0.99	7	14
AKT1	0.07	0.37	0.62	8	-0.9	4	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.041	0.38	0.59	10	-0.79	8	18
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	0.073	0.39	0.62	9	-0.84	6	15
THY1	0.1	0.53	0.86	8	-1.5	4	12
MYB	0.007	0.005	-10000	0	-10000	0	0
HMGA1	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	0.12	0.45	0.74	14	-0.81	6	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	0.074	0.41	0.67	9	-0.83	7	16
SP1	0.031	0.075	0.22	10	-0.096	5	15
INPP5D	0.009	0.003	-10000	0	-10000	0	0
SOCS5	-0.017	0.042	-10000	0	-0.096	10	10
STAT6 (dimer)/ETS1	0.064	0.48	0.71	7	-1	8	15
SOCS1	0.088	0.36	0.61	9	-0.7	6	15
SOCS3	0.095	0.36	0.67	8	-0.76	4	12
FCER2	0.13	0.49	0.94	8	-0.92	6	14
PARP14	0.014	0.021	0.089	5	-0.043	1	6
CCL17	0.1	0.54	0.93	7	-1.3	5	12
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.092	0.33	0.64	9	-0.61	6	15
T cell proliferation	0.078	0.49	0.79	6	-1.1	6	12
IL4R/JAK1	0.078	0.46	0.73	6	-1.1	6	12
EGR2	0.12	0.57	1.1	7	-1.2	6	13
JAK2	0.049	0.08	0.18	16	-10000	0	16
JAK3	0.006	0.018	0.075	2	-0.046	2	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.034	0.046	0.11	16	-10000	0	16
COL1A2	0.075	0.42	0.65	10	-1.2	5	15
CCL26	0.076	0.62	0.98	8	-1.3	9	17
IL4R	0.13	0.55	1.1	7	-1.3	4	11
PTPN6	-0.007	0.027	-10000	0	-0.057	10	10
IL13RA2	0.11	0.51	0.9	10	-1.3	4	14
IL13RA1	0.051	0.08	0.18	16	-10000	0	16
IRF4	0.055	0.35	0.57	7	-1.2	4	11
ARG1	0.12	0.24	0.61	6	-10000	0	6
CBL	0.092	0.4	0.68	10	-0.77	6	16
GTF3A	0.015	0.07	0.22	6	-0.11	8	14
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
IL13RA1/JAK2	0.077	0.12	0.27	16	-10000	0	16
IRF4/BCL6	0.014	0.3	0.39	5	-1.1	4	9
CD40LG	0.003	0.025	-10000	0	-0.099	4	4
MAPK14	0.097	0.4	0.69	10	-0.77	6	16
mitosis	0.074	0.36	0.6	9	-0.83	4	13
STAT6	0.16	0.64	1.2	10	-1.5	4	14
SPI1	0.01	0.002	-10000	0	-10000	0	0
RPS6KB1	0.07	0.35	0.59	8	-0.8	4	12
STAT6 (dimer)	0.16	0.64	1.2	10	-1.5	4	14
STAT6 (dimer)/PARP14	0.06	0.48	0.73	5	-1.1	7	12
mast cell activation	-0.015	0.03	-10000	0	-0.065	14	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.056	0.41	0.67	9	-0.8	8	17
FRAP1	0.07	0.37	0.62	8	-0.9	4	12
LTA	0.14	0.55	1.1	9	-1.3	4	13
FES	0.01	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	-0.17	0.63	1.4	4	-1.2	11	15
CCL11	0.086	0.46	0.75	6	-1.2	4	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.069	0.4	0.64	9	-0.8	7	16
IL2RG	0.003	0.016	0.075	2	-0.047	2	4
IL10	0.13	0.53	1	8	-1.3	4	12
IRS1	0.01	0.001	-10000	0	-10000	0	0
IRS2	0.01	0	-10000	0	-10000	0	0
IL4	0.14	0.27	0.75	7	-10000	0	7
IL5	0.11	0.5	0.88	7	-1.3	4	11
IL4/IL4R/JAK1/IL13RA1/JAK2	0.15	0.48	0.94	10	-0.92	4	14
COL1A1	0.054	0.51	0.78	8	-1.2	8	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	0.066	0.46	0.72	3	-1.3	4	7
IL2R gamma/JAK3	-0.005	0.054	0.12	2	-0.13	11	13
TFF3	0.073	0.59	0.86	9	-1.3	7	16
ALOX15	0.11	0.5	0.88	7	-1.3	4	11
MYBL1	0.01	0.002	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.1	0.47	0.8	8	-1	6	14
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	0.011	0.001	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	0.072	0.38	0.62	9	-0.74	8	17
mol:PI-3-4-5-P3	0.071	0.37	0.62	8	-0.9	4	12
PI3K	0.065	0.39	0.67	6	-0.82	6	12
DOK2	0.009	0.004	-10000	0	-10000	0	0
ETS1	-0.024	0.05	-10000	0	-0.1	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.092	0.32	0.6	10	-0.57	6	16
ITGB3	0.12	0.5	0.9	8	-1.3	4	12
PIGR	0.12	0.51	0.91	8	-1.3	4	12
IGHE	-0.045	0.089	0.14	1	-0.21	12	13
MAPKKK cascade	0.092	0.32	0.6	10	-0.56	6	16
BCL6	0.006	0.017	0.034	1	-0.061	5	6
OPRM1	0.11	0.5	0.88	7	-1.3	4	11
RETNLB	0.11	0.5	0.88	7	-1.3	4	11
SELP	0.098	0.56	0.92	10	-1.2	7	17
AICDA	0.089	0.46	0.84	4	-1.2	4	8

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.019	0.068	-10000	0	-0.13	20	20
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.065	0.21	2	-0.15	1	3
AP1	-0.014	0.073	0.17	3	-0.13	18	21
mol:PIP3	-0.031	0.045	-10000	0	-0.12	15	15
AKT1	-0.018	0.074	0.18	4	-0.14	5	9
PTK2B	-0.018	0.082	0.18	5	-0.15	12	17
RHOA	-0.006	0.052	0.16	4	-10000	0	4
PIK3CB	0.01	0.002	-10000	0	-0.008	1	1
mol:Ca2+	-0.001	0.038	0.14	2	-0.12	1	3
MAGI3	0.01	0.002	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.019	0.083	0.2	4	-0.15	17	21
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.076	0.16	5	-0.17	5	10
NF kappa B1 p50/RelA	-0.014	0.066	0.18	3	-0.14	11	14
endothelial cell migration	-0.054	0.12	0.15	1	-0.24	19	20
ADCY4	-0.037	0.13	0.21	6	-0.23	19	25
ADCY5	-0.043	0.13	0.22	5	-0.22	21	26
ADCY6	-0.033	0.12	0.21	6	-0.22	18	24
ADCY7	-0.035	0.12	0.21	6	-0.23	18	24
ADCY1	-0.039	0.15	0.23	5	-0.24	22	27
ADCY2	-0.05	0.15	0.21	6	-0.25	24	30
ADCY3	-0.033	0.12	0.21	6	-0.22	18	24
ADCY8	-0.032	0.12	0.24	5	-0.22	18	23
ADCY9	-0.033	0.12	0.21	6	-0.22	18	24
GSK3B	-0.019	0.078	0.17	5	-0.17	4	9
arachidonic acid secretion	-0.035	0.11	0.2	5	-0.2	18	23
GNG2	0.009	0.003	-10000	0	-0.008	1	1
TRIP6	0.005	0.023	-10000	0	-10000	0	0
GNAO1	-0.018	0.096	0.24	6	-0.14	18	24
HRAS	0.01	0	-10000	0	-10000	0	0
NFKBIA	-0.011	0.063	0.19	2	-0.16	1	3
GAB1	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.002	0.13	-10000	0	-0.82	2	2
JUN	0.01	0.002	0.017	1	-10000	0	1
LPA/LPA2/NHERF2	0.002	0.026	-10000	0	-0.058	11	11
TIAM1	-0.011	0.15	-10000	0	-0.95	2	2
PIK3R1	0.01	0.002	-10000	0	-0.008	1	1
mol:IP3	-0.001	0.039	0.14	2	-0.12	1	3
PLCB3	-0.006	0.033	0.1	5	-10000	0	5
FOS	0.009	0.003	-10000	0	-10000	0	0
positive regulation of mitosis	-0.035	0.11	0.2	5	-0.2	18	23
LPA/LPA1-2-3	-0.015	0.062	-10000	0	-0.13	17	17
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0.01	0	-10000	0	-10000	0	0
stress fiber formation	-0.012	0.082	0.2	5	-0.18	3	8
GNAZ	-0.021	0.099	0.24	6	-0.15	19	25
EGFR/PI3K-beta/Gab1	-0.021	0.053	-10000	0	-0.12	15	15
positive regulation of dendritic cell cytokine production	-0.015	0.062	-10000	0	-0.13	17	17
LPA/LPA2/MAGI-3	0	0.028	-10000	0	-0.061	12	12
ARHGEF1	-0.019	0.082	0.2	6	-0.14	14	20
GNAI2	-0.02	0.097	0.24	6	-0.14	19	25
GNAI3	-0.02	0.097	0.24	6	-0.14	19	25
GNAI1	-0.021	0.099	0.24	6	-0.15	19	25
LPA/LPA3	-0.006	0.024	-10000	0	-0.062	12	12
LPA/LPA2	-0.005	0.027	-10000	0	-0.063	14	14
LPA/LPA1	-0.033	0.08	-10000	0	-0.17	19	19
HB-EGF/EGFR	-0.005	0.043	0.18	1	-0.1	11	12
HBEGF	-0.001	0.022	0.072	3	-10000	0	3
mol:DAG	-0.001	0.039	0.14	2	-0.12	1	3
cAMP biosynthetic process	-0.031	0.13	0.23	6	-0.23	18	24
NFKB1	0.01	0	-10000	0	-10000	0	0
SRC	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0.002	-10000	0	-0.008	1	1
LYN	-0.011	0.063	0.19	2	-0.16	1	3
GNAQ	0.002	0.035	0.11	5	-10000	0	5
LPAR2	0.01	0.001	0.018	1	-10000	0	1
LPAR3	0.006	0.005	-10000	0	-0.002	5	5
LPAR1	-0.008	0.041	-10000	0	-0.11	11	11
IL8	-0.013	0.21	0.62	4	-0.37	9	13
PTK2	-0.015	0.081	0.21	6	-0.14	12	18
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
CASP3	-0.019	0.083	0.21	4	-0.15	17	21
EGFR	0.01	0.004	0.022	4	-10000	0	4
PLCG1	0.004	0.041	0.12	5	-0.14	1	6
PLD2	-0.015	0.081	0.21	6	-0.14	12	18
G12/G13	-0.015	0.066	-10000	0	-0.13	19	19
PI3K-beta	-0.027	0.057	-10000	0	-0.15	6	6
cell migration	-0.002	0.06	0.13	4	-0.24	2	6
SLC9A3R2	0.01	0	-10000	0	-10000	0	0
PXN	-0.012	0.083	0.2	5	-0.19	3	8
HRAS/GTP	-0.036	0.11	0.2	5	-0.21	18	23
RAC1	0.01	0	-10000	0	-10000	0	0
MMP9	0.007	0.005	-10000	0	-10000	0	0
PRKCE	0.01	0.001	-10000	0	-10000	0	0
PRKCD	-0.002	0.038	0.14	2	-0.12	1	3
Gi(beta/gamma)	-0.027	0.11	0.2	6	-0.2	18	24
mol:LPA	-0.018	0.037	-10000	0	-0.097	14	14
TRIP6/p130 Cas/FAK1/Paxillin	-0.006	0.088	0.2	5	-0.19	4	9
MAPKKK cascade	-0.035	0.11	0.2	5	-0.2	18	23
contractile ring contraction involved in cytokinesis	-0.005	0.052	0.16	4	-10000	0	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.002	0.032	0.11	4	-0.059	5	9
GNA15	0.002	0.035	0.11	5	-10000	0	5
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MAPT	-0.019	0.077	0.16	5	-0.17	5	10
GNA11	0.002	0.035	0.11	5	-0.059	6	11
Rac1/GTP	0.001	0.14	-10000	0	-0.87	2	2
MMP2	-0.054	0.12	0.15	1	-0.25	19	20

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.004	0.001	0	6	-10000	0	6
ADCY5	-0.004	0.001	0	10	-10000	0	10
ADCY6	-0.004	0	0	1	-10000	0	1
ADCY7	-0.004	0.001	0	2	-10000	0	2
ADCY1	-0.003	0.002	0	31	-10000	0	31
ADCY2	-0.002	0.002	0	36	-10000	0	36
ADCY3	-0.004	0	0	1	-10000	0	1
ADCY8	-0.003	0.001	0	8	-10000	0	8
PRKCE	-0.003	0	-10000	0	-10000	0	0
ADCY9	-0.004	0	0	1	-10000	0	1
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.013	0.084	0.14	14	-0.17	4	18

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.007	0.21	0.43	10	-0.4	9	19
IHH	0.022	0.067	0.15	13	-0.11	7	20
SHH Np/Cholesterol/GAS1	0.007	0.011	-10000	0	-0.089	1	1
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.007	0.011	0.089	1	-10000	0	1
SMO/beta Arrestin2	0.018	0.15	0.26	13	-0.25	11	24
SMO	0.013	0.15	0.28	12	-0.27	10	22
AKT1	0.017	0.094	0.23	3	-10000	0	3
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.009	0.004	-10000	0	-10000	0	0
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	0.017	0.16	0.28	13	-0.26	10	23
STIL	0.018	0.12	0.24	13	-0.2	7	20
DHH N/PTCH2	0.005	0.033	-10000	0	-0.12	5	5
DHH N/PTCH1	0.012	0.12	0.27	8	-0.21	10	18
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
DHH	0.008	0.004	-10000	0	-10000	0	0
PTHLH	0.005	0.3	0.49	13	-0.63	9	22
determination of left/right symmetry	0.017	0.16	0.28	13	-0.26	10	23
PIK3R1	0.01	0	-10000	0	-10000	0	0
skeletal system development	0.005	0.3	0.49	13	-0.62	9	22
IHH N/Hhip	0.01	0.049	0.11	9	-0.12	4	13
DHH N/Hhip	0.009	0.016	-10000	0	-0.12	1	1
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.017	0.16	0.28	13	-0.26	10	23
pancreas development	0.006	0.005	-10000	0	-10000	0	0
HHAT	0.01	0	-10000	0	-10000	0	0
PI3K	0.012	0.022	-10000	0	-0.12	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.01	0.002	-10000	0	-10000	0	0
somite specification	0.017	0.16	0.28	13	-0.26	10	23
SHH Np/Cholesterol/PTCH1	0.013	0.11	0.25	9	-0.21	7	16
SHH Np/Cholesterol/PTCH2	0.003	0.021	-10000	0	-0.09	4	4
SHH Np/Cholesterol/Megalin	-0.012	0.037	-10000	0	-0.089	15	15
SHH	-0.003	0.001	-10000	0	-10000	0	0
catabolic process	0.037	0.17	0.35	13	-0.27	7	20
SMO/Vitamin D3	0.007	0.13	0.29	10	-0.22	11	21
SHH Np/Cholesterol/Hhip	0.004	0.005	-10000	0	-10000	0	0
LRP2	0.006	0.005	-10000	0	-10000	0	0
receptor-mediated endocytosis	-0.008	0.14	0.29	9	-0.27	9	18
SHH Np/Cholesterol/BOC	-0.005	0.034	-10000	0	-0.089	11	11
SHH Np/Cholesterol/CDO	0.008	0.001	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.004	0.005	-10000	0	-10000	0	0
mol:Vitamin D3	0.014	0.12	0.29	10	-0.21	7	17
IHH N/PTCH2	0.006	0.061	0.11	9	-0.13	8	17
CDON	0.01	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.019	0.16	0.37	10	-0.27	7	17
Megalin/LRPAP1	-0.014	0.053	-10000	0	-0.12	15	15
PTCH2	0.01	0.002	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.007	0.001	-10000	0	-10000	0	0
PTCH1	0.037	0.17	0.35	13	-0.27	7	20
HHIP	0.006	0.005	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.008	0.004	-10000	0	-10000	0	0
GNB1/GNG2	-0.001	0.07	-10000	0	-0.13	15	15
mol:DAG	-0.003	0.07	0.15	3	-0.12	15	18
PLCG1	-0.003	0.072	0.15	3	-0.13	15	18
YES1	-0.005	0.067	0.088	14	-0.14	14	28
FZD3	0.01	0	-10000	0	-10000	0	0
FZD6	0.009	0.003	-10000	0	-10000	0	0
G protein	0.002	0.073	0.16	2	-0.13	15	17
MAP3K7	-0.006	0.074	0.18	5	-0.12	15	20
mol:Ca2+	0.002	0.076	0.16	5	-0.12	15	20
mol:IP3	-0.003	0.07	0.15	3	-0.12	15	18
NLK	-0.007	0.098	-10000	0	-0.88	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
CAMK2A	-0.006	0.07	0.16	4	-0.12	15	19
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.019	0.057	-10000	0	-0.14	14	14
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
GNAS	-0.005	0.067	-10000	0	-0.14	14	14
GO:0007205	-0.001	0.076	0.17	5	-0.12	15	20
WNT6	0.008	0.004	-10000	0	-10000	0	0
WNT4	0.01	0.002	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.006	0.067	-10000	0	-0.13	14	14
GNG2	0.01	0.002	-10000	0	-10000	0	0
WNT5A	0.009	0.004	-10000	0	-10000	0	0
WNT11	0.01	0.002	-10000	0	-10000	0	0
CDC42	-0.009	0.066	-10000	0	-0.13	15	15

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.05	0.25	0.43	3	-0.7	9	12
MKNK1	0.01	0	-10000	0	-10000	0	0
MAPK14	-0.004	0.093	0.16	5	-0.26	8	13
ATF2/c-Jun	-0.019	0.085	-10000	0	-0.22	9	9
MAPK11	-0.004	0.093	0.17	4	-0.26	8	12
MITF	-0.011	0.11	0.21	4	-0.31	8	12
MAPKAPK5	-0.011	0.11	0.21	4	-0.31	8	12
KRT8	-0.008	0.11	0.21	4	-0.31	8	12
MAPKAPK3	0.01	0	-10000	0	-10000	0	0
MAPKAPK2	0.01	0	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.006	0.13	0.25	4	-0.37	8	12
CEBPB	-0.011	0.11	0.21	4	-0.31	8	12
SLC9A1	-0.011	0.11	0.21	4	-0.31	8	12
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.008	0.11	0.24	5	-0.3	8	13
p38alpha-beta/MNK1	0.003	0.11	0.22	4	-0.29	8	12
JUN	-0.021	0.084	-10000	0	-0.22	9	9
PPARGC1A	-0.001	0.11	0.24	4	-0.36	5	9
USF1	-0.011	0.11	0.21	4	-0.31	8	12
RAB5/GDP/GDI1	-0.014	0.073	-10000	0	-0.22	9	9
NOS2	-0.013	0.14	0.43	1	-0.36	8	9
DDIT3	-0.011	0.11	0.21	4	-0.31	8	12
RAB5A	0.01	0	-10000	0	-10000	0	0
HSPB1	-0.013	0.087	0.15	4	-0.25	8	12
p38alpha-beta/HBP1	0.003	0.11	0.22	4	-0.29	8	12
CREB1	-0.016	0.12	0.21	4	-0.33	9	13
RAB5/GDP	0.008	0	-10000	0	-10000	0	0
EIF4E	-0.023	0.087	0.15	4	-0.26	8	12
RPS6KA4	-0.011	0.11	0.21	4	-0.31	8	12
PLA2G4A	-0.024	0.085	0.15	3	-0.26	8	11
GDI1	-0.011	0.11	0.21	4	-0.31	8	12
TP53	-0.019	0.13	0.23	4	-0.37	8	12
RPS6KA5	-0.011	0.11	0.21	4	-0.31	8	12
ESR1	-0.022	0.14	0.21	4	-0.4	8	12
HBP1	0.01	0	-10000	0	-10000	0	0
MEF2C	-0.011	0.11	0.21	4	-0.31	8	12
MEF2A	-0.011	0.11	0.21	4	-0.31	8	12
EIF4EBP1	-0.016	0.12	0.21	4	-0.33	9	13
KRT19	-0.018	0.14	0.26	3	-0.41	7	10
ELK4	-0.011	0.11	0.21	4	-0.31	8	12
ATF6	-0.011	0.11	0.21	4	-0.31	8	12
ATF1	-0.016	0.12	0.21	4	-0.33	9	13
p38alpha-beta/MAPKAPK2	0.003	0.11	0.22	4	-0.29	8	12
p38alpha-beta/MAPKAPK3	0.003	0.11	0.22	4	-0.29	8	12

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.16	0.51	1.4	1	-1.2	10	11
PLK1	-0.049	0.27	0.51	1	-1.2	4	5
BIRC5	-0.062	0.3	0.51	1	-1.2	5	6
HSPA1B	-0.16	0.52	1.8	1	-1.2	10	11
MAP2K1	0.008	0.07	0.33	2	-10000	0	2
BRCA2	-0.17	0.52	1.4	1	-1.3	10	11
FOXM1	-0.23	0.74	1.6	2	-1.7	11	13
XRCC1	-0.16	0.51	1.4	1	-1.2	10	11
FOXM1B/p19	-0.18	0.52	0.91	2	-1.2	11	13
Cyclin D1/CDK4	-0.15	0.47	1.1	1	-1.1	10	11
CDC2	-0.17	0.55	1.3	2	-1.2	11	13
TGFA	-0.15	0.46	1.1	1	-1	11	12
SKP2	-0.16	0.51	1.4	1	-1.2	10	11
CCNE1	0.003	0.02	0.077	2	-10000	0	2
CKS1B	-0.16	0.51	1.4	1	-1.2	10	11
RB1	-0.13	0.26	-10000	0	-0.61	12	12
FOXM1C/SP1	-0.2	0.57	1.1	1	-1.4	11	12
AURKB	-0.076	0.32	0.51	1	-1.2	6	7
CENPF	-0.18	0.54	1.8	1	-1.2	11	12
CDK4	0.005	0.03	0.12	2	-10000	0	2
MYC	-0.14	0.44	1.1	1	-1	10	11
CHEK2	0.008	0.07	0.33	2	-10000	0	2
ONECUT1	-0.18	0.48	1.2	1	-1.1	11	12
CDKN2A	0.009	0.005	-10000	0	-10000	0	0
LAMA4	-0.16	0.51	1.4	1	-1.2	10	11
FOXM1B/HNF6	-0.23	0.59	1.2	1	-1.4	11	12
FOS	-0.18	0.55	1.8	1	-1.2	12	13
SP1	0.011	0	-10000	0	-10000	0	0
CDC25B	-0.17	0.52	1.4	1	-1.2	10	11
response to radiation	0.004	0.056	0.27	2	-10000	0	2
CENPB	-0.16	0.51	1.4	1	-1.2	10	11
CENPA	-0.18	0.56	1.8	1	-1.2	12	13
NEK2	-0.2	0.57	1.8	1	-1.2	13	14
HIST1H2BA	-0.16	0.5	1.4	1	-1.2	10	11
CCNA2	0.004	0.02	0.077	2	-10000	0	2
EP300	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.21	0.61	1.6	1	-1.5	10	11
CCNB2	-0.17	0.53	1.4	1	-1.3	10	11
CCNB1	-0.17	0.55	1.8	1	-1.3	10	11
ETV5	-0.16	0.51	1.4	1	-1.2	10	11
ESR1	-0.23	0.58	1.2	2	-1.1	19	21
CCND1	-0.15	0.48	1.2	1	-1.1	10	11
GSK3A	0.008	0.061	0.28	2	-10000	0	2
Cyclin A-E1/CDK1-2	0.009	0.071	0.27	2	-0.13	6	8
CDK2	0.003	0.02	0.077	2	-10000	0	2
G2/M transition of mitotic cell cycle	0.003	0.065	0.31	2	-10000	0	2
FOXM1B/Cbp/p300	-0.21	0.51	-10000	0	-1.3	11	11
GAS1	-0.17	0.52	1.4	1	-1.2	11	12
MMP2	-0.23	0.6	1.4	2	-1.1	19	21
RB1/FOXM1C	-0.17	0.5	1	1	-1.1	11	12
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.012	0.007	0.024	11	-0.007	1	12
GNB1/GNG2	-0.021	0.051	-10000	0	-0.18	6	6
AKT1	0.056	0.18	0.42	13	-0.22	3	16
EGF	0.007	0.005	-10000	0	-10000	0	0
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.005	0.039	0.11	3	-0.11	6	9
mol:Ca2+	0.058	0.23	0.5	13	-0.3	9	22
LYN	0.003	0.049	0.12	7	-0.1	3	10
RhoA/GTP	-0.009	0.042	-10000	0	-0.12	9	9
mol:PGI2	0	0.001	-10000	0	-10000	0	0
SYK	0.058	0.24	0.51	13	-0.36	5	18
GNG2	0.01	0.003	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0	0.056	-10000	0	-0.24	3	3
G beta5/gamma2	-0.025	0.065	-10000	0	-0.25	5	5
PRKCH	0.057	0.24	0.51	13	-0.37	6	19
DNM1	0.009	0.003	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.006	0.02	-10000	0	-10000	0	0
mol:GTP	0.002	0.006	0.018	7	-10000	0	7
PTGDR	0.006	0.005	-10000	0	-10000	0	0
G12 family/GTP	-0.028	0.092	-10000	0	-0.28	9	9
ADRBK1	0.01	0.001	-10000	0	-10000	0	0
ADRBK2	0.01	0.001	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.015	0.004	-10000	0	-10000	0	0
mol:GDP	-0.049	0.16	0.22	4	-0.37	13	17
mol:NADP	0.01	0.002	0.017	1	-10000	0	1
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	0.009	0.004	0.017	1	-10000	0	1
mol:IP3	0.055	0.26	0.53	13	-0.38	9	22
cell morphogenesis	0.015	0.004	-10000	0	-10000	0	0
PLCB2	0.045	0.3	0.56	13	-0.53	9	22
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.004	0.042	0.11	3	-0.13	5	8
mol:PDG2	0	0.001	-10000	0	-10000	0	0
HCK	-0.001	0.041	0.11	5	-0.1	5	10
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.01	0.003	-10000	0	-10000	0	0
PRKCB1	0.056	0.25	0.52	13	-0.38	7	20
GNAQ	0.01	0	-10000	0	-10000	0	0
mol:L-citrulline	0.01	0.002	0.017	1	-10000	0	1
TXA2/TXA2-R family	0.053	0.29	0.57	13	-0.56	5	18
LCK	-0.009	0.041	0.12	2	-0.13	6	8
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0	0.034	0.082	1	-0.11	5	6
TXA2-R family/G12 family/GDP/G beta/gamma	0.007	0.021	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.006	0.038	0.082	5	-0.11	5	10
MAPK14	0.055	0.2	0.44	13	-0.24	5	18
TGM2/GTP	0.056	0.27	0.55	13	-0.42	9	22
MAPK11	0.055	0.2	0.44	13	-0.24	5	18
ARHGEF1	0.045	0.16	0.35	13	-0.19	5	18
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	0.061	0.25	0.54	13	-0.4	5	18
RAB11/GDP	0.005	0.014	-10000	0	-0.023	13	13
ICAM1	0.06	0.22	0.48	13	-0.29	5	18
cAMP biosynthetic process	0.052	0.24	0.5	13	-0.35	9	22
Gq family/GTP/EBP50	0.004	0.025	0.078	3	-0.12	2	5
actin cytoskeleton reorganization	0.015	0.004	-10000	0	-10000	0	0
SRC	0.003	0.049	0.12	7	-0.1	5	12
GNB5	0.01	0.002	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.011	0.1	0.2	12	-0.15	9	21
VCAM1	0.064	0.24	0.53	13	-0.35	5	18
TP beta/Gq family/GDP/G beta5/gamma2	0	0.056	-10000	0	-0.24	3	3
platelet activation	0.06	0.23	0.51	13	-0.32	5	18
PGI2/IP	0.002	0.028	-10000	0	-0.12	4	4
PRKACA	-0.002	0.034	-10000	0	-0.13	5	5
Gq family/GDP/G beta5/gamma2	-0.003	0.055	-10000	0	-0.24	3	3
TXA2/TP beta/beta Arrestin2	-0.008	0.068	-10000	0	-0.35	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.003	0.036	0.14	1	-0.12	5	6
mol:DAG	0.055	0.27	0.55	13	-0.41	9	22
EGFR	0.01	0.002	-10000	0	-10000	0	0
TXA2/TP alpha	0.049	0.28	0.56	13	-0.48	9	22
Gq family/GTP	-0.003	0.027	-10000	0	-0.14	3	3
YES1	0.003	0.049	0.12	7	-0.1	5	12
GNAI2/GTP	0.001	0.032	-10000	0	-0.1	6	6
PGD2/DP	0.004	0.015	-10000	0	-0.12	1	1
SLC9A3R1	0.01	0	-10000	0	-10000	0	0
FYN	0.003	0.049	0.12	7	-0.1	5	12
mol:NO	0.01	0.002	0.017	1	-10000	0	1
GNA15	0.01	0.001	-10000	0	-10000	0	0
PGK/cGMP	0.005	0.03	-10000	0	-0.098	6	6
RhoA/GDP	0.005	0.014	-10000	0	-0.023	13	13
TP alpha/TGM2/GDP/G beta/gamma	0.009	0.044	-10000	0	-0.13	5	5
NOS3	0.01	0.002	0.017	1	-10000	0	1
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	0.056	0.24	0.51	13	-0.37	6	19
PRKCB	0.063	0.25	0.53	13	-0.37	6	19
PRKCE	0.056	0.24	0.51	13	-0.38	5	18
PRKCD	0.057	0.25	0.52	13	-0.4	5	18
PRKCG	0.056	0.25	0.53	13	-0.39	7	20
muscle contraction	0.053	0.28	0.56	13	-0.5	6	19
PRKCZ	0.058	0.24	0.51	13	-0.36	5	18
ARR3	0.004	0.005	-10000	0	-10000	0	0
TXA2/TP beta	0.015	0.051	0.13	7	-0.12	5	12
PRKCQ	0.059	0.24	0.52	13	-0.38	6	19
MAPKKK cascade	0.05	0.27	0.54	13	-0.44	9	22
SELE	0.063	0.23	0.51	13	-0.3	5	18
TP beta/GNAI2/GDP/G beta/gamma	0.012	0.041	-10000	0	-0.11	5	5
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	0.009	0.003	-10000	0	-10000	0	0
chemotaxis	0.055	0.3	0.6	13	-0.6	5	18
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.005	0.034	2	-10000	0	2

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.009	0.027	-10000	0	-0.14	2	2
PDGFRB	0.008	0.008	0.024	3	-0.011	10	13
SPHK1	-0.032	0.13	-10000	0	-0.59	4	4
mol:S1P	-0.032	0.11	-10000	0	-0.5	4	4
S1P1/S1P/Gi	-0.02	0.13	0.39	3	-0.29	11	14
GNAO1	0.008	0.012	0.05	3	-0.021	7	10
PDGFB-D/PDGFRB/PLCgamma1	-0.016	0.13	0.32	4	-0.3	8	12
PLCG1	-0.017	0.13	0.34	4	-0.27	11	15
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.008	0.024	3	-0.011	10	13
GNAI2	0.009	0.013	0.05	3	-0.022	8	11
GNAI3	0.009	0.012	0.044	3	-0.02	8	11
GNAI1	0.008	0.012	0.044	3	-0.02	8	11
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.005	0.034	0.12	3	-0.13	2	5
S1P1/S1P	-0.025	0.094	0.21	2	-0.3	6	8
negative regulation of cAMP metabolic process	-0.019	0.13	0.39	3	-0.28	11	14
MAPK3	-0.033	0.18	0.4	4	-0.5	8	12
calcium-dependent phospholipase C activity	0	0.005	0.018	4	-0.009	8	12
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
KDR	0.008	0.009	0.029	3	-0.017	8	11
PLCB2	-0.016	0.1	0.21	4	-0.28	6	10
RAC1	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.025	0.077	-10000	0	-0.19	12	12
receptor internalization	-0.024	0.089	0.2	2	-0.28	6	8
PTGS2	-0.069	0.29	0.53	3	-0.86	8	11
Rac1/GTP	-0.025	0.077	-10000	0	-0.19	12	12
RHOA	0.01	0	-10000	0	-10000	0	0
VEGFA	0.008	0.008	0.028	2	-0.018	6	8
negative regulation of T cell proliferation	-0.019	0.13	0.39	3	-0.28	11	14
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.008	0.012	0.044	3	-0.02	8	11
MAPK1	-0.033	0.18	0.4	4	-0.5	8	12
S1P1/S1P/PDGFB-D/PDGFRB	-0.014	0.1	0.26	4	-0.21	12	16
ABCC1	0.008	0.008	0.023	3	-0.016	8	11

×

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

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
BAG4	0.01	0.002	-10000	0	-10000	0	0
Caspase 8 (4 units)	-0.021	0.066	-10000	0	-0.14	18	18
NEF	-0.01	0.029	-10000	0	-0.1	7	7
NFKBIA	0.016	0.042	0.11	10	-0.063	8	18
BIRC3	-0.032	0.071	-10000	0	-0.24	8	8
CYCS	0.004	0.13	0.28	11	-0.15	18	29
RIPK1	0.01	0	-10000	0	-10000	0	0
CD247	-0.001	0.032	-10000	0	-0.11	6	6
MAP2K7	0.011	0.13	0.28	11	-0.21	1	12
protein ubiquitination	0.012	0.093	0.22	10	-0.16	1	11
CRADD	0.01	0	-10000	0	-10000	0	0
DAXX	0.01	0	-10000	0	-10000	0	0
FAS	0.009	0.003	-10000	0	-10000	0	0
BID	-0.012	0.11	0.26	7	-0.15	18	25
NF-kappa-B/RelA/I kappa B alpha	0.003	0.052	-10000	0	-0.15	8	8
TRADD	0.01	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.004	-10000	0	-10000	0	0
CFLAR	0.01	0	-10000	0	-10000	0	0
FADD	0.01	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.003	0.053	-10000	0	-0.15	8	8
MAPK8	0.008	0.12	0.27	11	-0.2	1	12
APAF1	0.01	0.002	-10000	0	-10000	0	0
TRAF1	0.01	0	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.01	0.11	0.28	7	-0.16	18	25
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.012	0.059	0.17	2	-0.2	1	3
CHUK	0.011	0.096	0.23	10	-0.17	1	11
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.011	0.042	-10000	0	-0.088	12	12
TCRz/NEF	-0.019	0.063	-10000	0	-0.16	13	13
TNF	0.007	0.005	-10000	0	-10000	0	0
FASLG	-0.027	0.091	0.14	2	-0.21	13	15
NFKB1	0.016	0.042	0.11	10	-0.063	8	18
TNFR1A/BAG4/TNF-alpha	0.013	0.023	-10000	0	-0.1	3	3
CASP6	-0.01	0.071	0.26	1	-10000	0	1
CASP7	0.016	0.23	0.5	11	-0.36	8	19
RELA	0.016	0.042	0.11	10	-0.063	8	18
CASP2	0.01	0	-10000	0	-10000	0	0
CASP3	0.016	0.23	0.46	13	-0.36	8	21
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.012	0.022	-10000	0	-0.12	2	2
CASP8	0.01	0	-10000	0	-10000	0	0
CASP9	0.01	0	-10000	0	-10000	0	0
MAP3K14	0.013	0.1	0.24	10	-0.19	1	11
APAF-1/Caspase 9	-0.053	0.068	-10000	0	-0.16	17	17
BCL2	0.005	0.12	0.26	11	-0.19	1	12

×

Coregulation of Androgen receptor activity

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
NRIP1	0.007	0.022	0.045	4	-0.081	4	8
SVIL	0.007	0.019	0.036	4	-0.071	4	8
ZNF318	0.014	0.037	0.16	4	-0.056	4	8
JMJD2C	0.015	0.048	0.18	6	-10000	0	6
T-DHT/AR/Ubc9	0.02	0.065	0.16	10	-0.1	2	12
CARM1	0.009	0.007	-10000	0	-0.019	4	4
PRDX1	0.009	0.006	0.022	4	-0.017	4	8
PELP1	0.01	0.008	0.035	4	-0.016	4	8
CTNNB1	0.008	0.016	0.031	4	-0.057	4	8
AKT1	0.01	0.013	0.053	4	-0.032	4	8
PTK2B	0.008	0.015	0.034	4	-0.054	4	8
MED1	0.011	0.014	0.059	4	-0.028	4	8
MAK	0.01	0.032	0.16	3	-0.054	4	7
response to oxidative stress	0	0.004	0.011	4	-0.012	4	8
HIP1	0.007	0.019	0.036	4	-0.071	4	8
GSN	0.007	0.022	0.045	4	-0.081	4	8
NCOA2	0.008	0.007	-10000	0	-0.019	4	4
NCOA6	0.008	0.018	0.037	4	-0.067	4	8
DNA-PK	0.024	0.036	0.17	4	-10000	0	4
NCOA4	0.009	0.006	0.018	1	-0.015	4	5
PIAS3	0.008	0.016	0.031	4	-0.057	4	8
cell proliferation	-0.007	0.075	0.15	1	-0.44	2	3
XRCC5	0.01	0.011	0.044	4	-0.023	4	8
UBE3A	0.006	0.028	0.05	4	-0.11	4	8
T-DHT/AR/SNURF	0.003	0.052	0.13	6	-0.1	6	12
FHL2	-0.037	0.18	0.47	1	-0.65	6	7
RANBP9	0.008	0.018	0.037	4	-0.067	4	8
JMJD1A	0.013	0.064	0.21	6	-0.12	4	10
CDK6	0.009	0.005	-10000	0	-0.011	4	4
TGFB1I1	0.007	0.019	0.036	4	-0.071	4	8
T-DHT/AR/CyclinD1	0.018	0.069	0.17	10	-0.1	2	12
XRCC6	0.01	0.011	0.044	4	-0.023	4	8
T-DHT/AR	0.034	0.12	0.3	10	-10000	0	10
CTDSP1	0.009	0.009	0.022	2	-0.029	4	6
CTDSP2	0.013	0.026	0.11	4	-0.044	4	8
BRCA1	0.007	0.019	0.036	4	-0.071	4	8
TCF4	0.012	0.02	0.087	4	-0.038	3	7
CDKN2A	0.01	0.014	0.058	4	-0.028	4	8
SRF	0.005	0.045	0.21	1	-0.12	6	7
NKX3-1	-0.029	0.15	0.46	1	-0.64	4	5
KLK3	-0.03	0.27	0.5	4	-1.1	4	8
TMF1	0.009	0.007	0.021	1	-0.021	4	5
HNRNPA1	0.011	0.014	0.058	4	-0.028	4	8
AOF2	-0.002	0.015	0.026	4	-0.062	4	8
APPL1	-0.003	0.025	0.097	4	-0.047	4	8
T-DHT/AR/Caspase 8	0.016	0.054	0.14	8	-0.1	2	10
AR	0.012	0.042	0.096	10	-0.054	10	20
UBA3	0.009	0.009	0.021	1	-0.029	4	5
PATZ1	0.011	0.014	0.058	4	-0.028	4	8
PAWR	0.008	0.008	0.023	2	-0.021	4	6
PRKDC	0.01	0.011	0.044	4	-0.023	4	8
PA2G4	0.012	0.017	0.077	4	-0.031	4	8
UBE2I	0.01	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.02	0.059	0.15	9	-0.09	2	11
RPS6KA3	0.007	0.022	0.045	4	-0.081	4	8
T-DHT/AR/ARA70	0.019	0.068	0.16	10	-0.1	2	12
LATS2	0.011	0.014	0.063	4	-0.025	4	8
T-DHT/AR/PRX1	0.015	0.051	0.13	10	-0.09	2	12
Cyclin D3/CDK11 p58	0.007	0.005	-10000	0	-10000	0	0
VAV3	0.007	0.014	0.031	4	-0.057	3	7
KLK2	0.015	0.1	0.46	4	-10000	0	4
CASP8	0.01	0.009	0.031	4	-0.023	4	8
T-DHT/AR/TIF2/CARM1	0.012	0.064	0.15	9	-0.099	7	16
TMPRSS2	-0.001	0.087	0.47	2	-10000	0	2
CCND1	0.008	0.011	0.024	1	-0.039	4	5
PIAS1	0.006	0.028	0.05	4	-0.11	4	8
mol:T-DHT	0.006	0.039	0.087	10	-0.051	10	20
CDC2L1	0	0.002	-10000	0	-10000	0	0
PIAS4	0.005	0.038	0.062	4	-0.16	4	8
T-DHT/AR/CDK6	0.019	0.067	0.15	10	-0.12	3	13
CMTM2	0.007	0.008	0.027	3	-0.013	4	7
SNURF	0.008	0.004	-10000	0	-10000	0	0
ZMIZ1	0.014	0.043	0.099	10	-0.056	10	20
CCND3	0.01	0.005	-10000	0	-0.01	4	4
TGIF1	0.011	0.014	0.058	4	-0.028	4	8
FKBP4	0.008	0.018	0.037	4	-0.067	4	8

×

Osteopontin-mediated events

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
IKK alpha homodimer	0.016	0.078	0.13	21	-10000	0	21
NF kappa B1 p50/RelA/I kappa B alpha	0.028	0.087	0.21	5	-10000	0	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.018	0.053	-10000	0	-0.13	15	15
AP1	-0.014	0.091	-10000	0	-0.18	10	10
ILK	0.024	0.094	0.15	24	-10000	0	24
bone resorption	0.017	0.08	0.13	23	-10000	0	23
PTK2B	0.01	0	-10000	0	-10000	0	0
PYK2/p130Cas	-0.004	0.048	0.12	2	-0.089	15	17
ITGAV	0.007	0.015	-10000	0	-0.055	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.015	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.01	0.048	-10000	0	-0.11	14	14
MAP3K1	0.025	0.095	0.16	19	-10000	0	19
JUN	0.008	0.011	0.032	5	-0.013	13	18
MAPK3	0.025	0.091	0.23	5	-10000	0	5
MAPK1	0.025	0.091	0.23	5	-10000	0	5
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.021	0.097	0.27	5	-10000	0	5
ITGB3	0.006	0.015	-10000	0	-0.055	2	2
NFKBIA	0.022	0.093	0.23	5	-10000	0	5
FOS	0.007	0.01	0.031	3	-0.013	12	15
CD44	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
PLAU	0.007	0.17	0.41	1	-0.87	2	3
NF kappa B1 p50/RelA	0.014	0.075	0.23	1	-0.19	2	3
BCAR1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.007	0.032	0.077	1	-0.1	4	5
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.023	0.09	0.16	18	-10000	0	18
VAV3	0.017	0.084	0.15	15	-0.18	1	16
MAP3K14	0.024	0.092	0.24	4	-10000	0	4
ROCK2	0.01	0	-10000	0	-10000	0	0
SPP1	0.003	0.008	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.001	0.073	0.12	16	-0.16	2	18
MMP2	-0.025	0.11	0.22	2	-0.25	10	12

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.005	0.04	-10000	0	-0.1	12	12
EFNA5	0.01	0.002	-10000	0	-10000	0	0
FYN	-0.01	0.045	0.14	4	-0.091	12	16
neuron projection morphogenesis	-0.005	0.04	-10000	0	-0.1	12	12
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.005	0.04	-10000	0	-0.1	12	12
EPHA5	0.008	0.004	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0.01	0.002	-10000	0	-10000	0	0
EPHB2	0.01	0.005	0.02	6	-10000	0	6
EFNB1	0	0.008	0.016	13	-10000	0	13
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.037	-10000	0	-0.077	12	12
Ephrin B2/EPHB1-2	0.002	0.04	-10000	0	-0.094	11	11
neuron projection morphogenesis	0.001	0.033	-10000	0	-0.074	12	12
Ephrin B1/EPHB1-2/Tiam1	0.004	0.038	-10000	0	-0.081	12	12
DNM1	0.01	0.004	0.017	1	-10000	0	1
cell-cell signaling	0.001	0.004	0.011	5	-10000	0	5
MAP2K4	-0.065	0.17	-10000	0	-0.48	11	11
YES1	-0.089	0.24	-10000	0	-0.68	11	11
Ephrin B1/EPHB1-2/NCK2	0.003	0.038	-10000	0	-0.08	13	13
PI3K	-0.05	0.17	-10000	0	-0.48	11	11
mol:GDP	0.003	0.037	-10000	0	-0.08	12	12
ITGA2B	0.008	0.004	-10000	0	-10000	0	0
endothelial cell proliferation	0.013	0.013	-10000	0	-0.097	1	1
FYN	-0.089	0.24	-10000	0	-0.68	11	11
MAP3K7	-0.069	0.18	-10000	0	-0.5	11	11
FGR	-0.094	0.24	-10000	0	-0.69	11	11
TIAM1	0.009	0.003	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.062	0.16	-10000	0	-0.44	11	11
LYN	-0.089	0.24	-10000	0	-0.68	11	11
Ephrin B1/EPHB1-2/Src Family Kinases	-0.086	0.22	-10000	0	-0.64	11	11
Ephrin B1/EPHB1-2	-0.072	0.18	-10000	0	-0.53	11	11
SRC	-0.089	0.24	-10000	0	-0.68	11	11
ITGB3	0.01	0.002	-10000	0	-10000	0	0
EPHB1	0.009	0.005	0.02	2	-10000	0	2
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.013	0.013	-10000	0	-0.097	1	1
alphaIIb/beta3 Integrin	-0.004	0.046	-10000	0	-0.12	10	10
BLK	-0.099	0.24	-10000	0	-0.69	11	11
HCK	-0.091	0.24	-10000	0	-0.68	11	11
regulation of stress fiber formation	-0.003	0.038	0.079	13	-10000	0	13
MAPK8	-0.064	0.16	-10000	0	-0.46	11	11
Ephrin B1/EPHB1-2/RGS3	0.003	0.038	-10000	0	-0.08	13	13
endothelial cell migration	-0.057	0.14	-10000	0	-0.41	11	11
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	0.008	0.006	0.02	3	-10000	0	3
regulation of focal adhesion formation	-0.003	0.038	0.079	13	-10000	0	13
chemotaxis	-0.003	0.038	0.079	13	-10000	0	13
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.004	0.035	-10000	0	-0.075	12	12
angiogenesis	-0.071	0.18	-10000	0	-0.53	11	11
LCK	-0.1	0.24	-10000	0	-0.7	11	11

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.002	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0.001	0.003	0.009	7	-10000	0	7
cytokine production during immune response	-0.033	0.22	0.41	6	-0.6	7	13
IL27/IL27R/JAK1	-0.016	0.17	0.57	1	-0.78	2	3
TBX21	-0.033	0.17	0.4	6	-0.35	6	12
IL12B	0.005	0.015	0.057	6	-10000	0	6
IL12A	0.005	0.025	0.059	8	-10000	0	8
IL6ST	0.016	0.037	0.11	9	-10000	0	9
IL27RA/JAK1	-0.008	0.16	0.3	1	-0.91	2	3
IL27	0.011	0.032	0.1	7	-10000	0	7
TYK2	0.022	0.041	0.14	8	-10000	0	8
T-helper cell lineage commitment	0.007	0.037	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.033	0.22	0.41	6	-0.6	7	13
T cell proliferation during immune response	-0.033	0.22	0.41	6	-0.6	7	13
MAPKKK cascade	0.033	0.22	0.6	7	-0.41	6	13
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.005	0.013	0.031	6	-0.012	23	29
IL12RB1	0.007	0.005	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.003	0.28	0.8	7	-0.62	1	8
IL27/IL27R/JAK2/TYK2	0.033	0.22	0.6	7	-0.42	6	13
positive regulation of T cell mediated cytotoxicity	0.033	0.22	0.6	7	-0.41	6	13
STAT1 (dimer)	-0.062	0.15	0.43	1	-0.64	2	3
JAK2	0.019	0.026	0.087	9	-10000	0	9
JAK1	0.01	0.02	0.044	14	-0.011	24	38
STAT2 (dimer)	0.027	0.2	0.5	7	-0.4	6	13
T cell proliferation	0.034	0.21	0.56	7	-0.4	6	13
IL12/IL12R/TYK2/JAK2	0.027	0.17	0.53	7	-10000	0	7
IL17A	0.007	0.037	-10000	0	-10000	0	0
mast cell activation	-0.033	0.22	0.41	6	-0.6	7	13
IFNG	0.031	0.11	0.34	8	-10000	0	8
T cell differentiation	-0.003	0.005	0.017	1	-0.02	2	3
STAT3 (dimer)	0.027	0.2	0.5	7	-0.4	6	13
STAT5A (dimer)	0.027	0.2	0.5	7	-0.4	6	13
STAT4 (dimer)	-0.013	0.14	0.41	1	-0.41	6	7
STAT4	0.008	0.004	-10000	0	-10000	0	0
T cell activation	-0.003	0.02	0.12	1	-0.13	1	2
IL27R/JAK2/TYK2	-0.005	0.18	0.43	4	-0.86	2	6
GATA3	-0.011	0.17	-10000	0	-1	2	2
IL18	-0.002	0.003	0.014	2	-10000	0	2
positive regulation of mast cell cytokine production	0.027	0.2	0.5	7	-0.39	6	13
IL27/EBI3	0.007	0.044	0.18	2	-0.12	3	5
IL27RA	0.007	0.19	0.43	4	-0.99	2	6
IL6	0.006	0.005	-10000	0	-10000	0	0
STAT5A	0.01	0	-10000	0	-10000	0	0
monocyte differentiation	0.002	0.005	0.017	8	-10000	0	8
IL2	-0.005	0.1	0.44	2	-0.59	1	3
IL1B	-0.001	0.004	0.016	4	-10000	0	4
EBI3	0.008	0.022	0.11	2	-10000	0	2
TNF	-0.001	0.004	0.014	4	-10000	0	4

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.018	0.12	0.29	3	-0.25	12	15
IKBKB	0.007	0.075	0.23	2	-0.17	3	5
AKT1	0.011	0.11	0.27	7	-0.15	8	15
IKBKG	0.003	0.075	0.19	3	-0.18	3	6
CALM1	-0.028	0.096	0.15	1	-0.24	9	10
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
MAP3K1	-0.023	0.16	0.3	5	-0.34	11	16
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.1	0.16	1	-0.24	10	11
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.012	0.076	0.17	3	-0.16	10	13
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.009	0.004	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	-0.007	0.049	-10000	0	-0.12	12	12
CD22	-0.026	0.1	-10000	0	-0.29	9	9
CAMK2G	-0.028	0.091	0.15	1	-0.23	9	10
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.009	0.003	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.011	0.043	-10000	0	-0.091	17	17
GO:0007205	-0.027	0.1	0.16	1	-0.26	9	10
SYK	0.01	0.002	-10000	0	-10000	0	0
ELK1	-0.028	0.097	0.16	1	-0.24	9	10
NFATC1	-0.013	0.11	0.22	4	-0.25	8	12
B-cell antigen/BCR complex	-0.007	0.049	-10000	0	-0.12	12	12
PAG1/CSK	0.01	0.026	-10000	0	-0.12	3	3
NFKBIB	0.01	0.031	0.12	2	-10000	0	2
HRAS	-0.022	0.084	0.15	1	-0.21	9	10
NFKBIA	0.01	0.031	0.12	2	-10000	0	2
NF-kappa-B/RelA/I kappa B beta	0.012	0.029	0.1	3	-10000	0	3
RasGAP/Csk	-0.001	0.055	-10000	0	-0.11	15	15
mol:GDP	-0.03	0.1	0.16	1	-0.26	9	10
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	0.009	0.003	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.012	0.029	0.1	3	-10000	0	3
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.018	0.18	0.34	5	-0.36	12	17
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.025	0.1	0.16	1	-0.25	10	11
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.027	0.092	0.15	1	-0.23	9	10
CHUK	0.003	0.075	0.19	3	-0.18	3	6
IBTK	0.01	0.002	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.027	0.11	0.11	7	-0.26	11	18
PTPN6	-0.02	0.1	0.13	3	-0.28	9	12
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.013	0.031	0.093	7	-10000	0	7
VAV2	-0.035	0.12	0.22	1	-0.3	10	11
ubiquitin-dependent protein catabolic process	0.011	0.031	0.12	2	-10000	0	2
BTK	-0.046	0.2	-10000	0	-0.66	7	7
CD19	-0.039	0.11	-10000	0	-0.28	10	10
MAP4K1	0.009	0.003	-10000	0	-10000	0	0
CD72	0.01	0.002	-10000	0	-10000	0	0
PAG1	0.01	0.002	-10000	0	-10000	0	0
MAPK14	-0.019	0.15	0.29	5	-0.3	11	16
SH3BP5	0.01	0	-10000	0	-10000	0	0
PIK3AP1	-0.033	0.11	-10000	0	-0.28	11	11
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.019	0.1	-10000	0	-0.28	9	9
RAF1	-0.022	0.08	0.14	1	-0.2	9	10
RasGAP/p62DOK/SHIP	-0.006	0.057	-10000	0	-0.11	17	17
CD79A	0.009	0.004	-10000	0	-10000	0	0
re-entry into mitotic cell cycle	-0.012	0.076	0.16	3	-0.16	10	13
RASA1	0.01	0.001	-10000	0	-10000	0	0
MAPK3	-0.022	0.07	0.13	1	-0.2	6	7
MAPK1	-0.022	0.07	0.13	1	-0.2	6	7
CD72/SHP1	-0.016	0.13	0.24	5	-0.25	13	18
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.023	0.14	0.31	4	-0.3	11	15
actin cytoskeleton organization	-0.01	0.14	0.28	5	-0.27	10	15
NF-kappa-B/RelA	0.025	0.056	0.19	3	-10000	0	3
Calcineurin	-0.019	0.087	-10000	0	-0.21	10	10
PI3K	-0.038	0.082	-10000	0	-0.2	13	13
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.037	0.1	-10000	0	-0.27	10	10
SOS1	0.01	0.001	-10000	0	-10000	0	0
Bam32/HPK1	-0.052	0.17	-10000	0	-0.48	9	9
DAPP1	-0.063	0.18	-10000	0	-0.51	9	9
cytokine secretion	-0.012	0.1	0.21	4	-0.23	8	12
mol:DAG	-0.025	0.1	0.16	1	-0.25	10	11
PLCG2	0.01	0.002	-10000	0	-10000	0	0
MAP2K1	-0.022	0.075	0.14	1	-0.19	9	10
B-cell antigen/BCR complex/FcgammaRIIB	-0.01	0.056	-10000	0	-0.12	15	15
mol:PI-3-4-5-P3	-0.022	0.071	0.11	1	-0.16	12	13
ETS1	-0.029	0.088	0.14	1	-0.22	10	11
B-cell antigen/BCR complex/LYN/SYK/BLNK	0	0.051	-10000	0	-0.097	16	16
B-cell antigen/BCR complex/LYN	-0.045	0.11	-10000	0	-0.3	10	10
MALT1	0.01	0.001	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.011	0.14	0.28	5	-0.28	10	15
B-cell antigen/BCR complex/LYN/SYK	-0.022	0.11	0.14	6	-0.22	13	19
CARD11	-0.012	0.13	0.18	4	-0.27	11	15
FCGR2B	0.008	0.004	-10000	0	-10000	0	0
PPP3CA	0.01	0.001	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.011	0.045	0.15	4	-10000	0	4
PTPRC	0.007	0.005	-10000	0	-10000	0	0
PDPK1	0.009	0.098	0.22	8	-0.13	9	17
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.011	0.03	0.11	5	-10000	0	5

×

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

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
MAP4K1	-0.033	0.13	0.28	1	-0.36	9	10
CRKL	-0.036	0.13	0.29	1	-0.37	9	10
HRAS	-0.041	0.13	0.27	1	-0.34	9	10
mol:PIP3	-0.034	0.12	0.28	1	-0.35	9	10
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	-0.032	0.13	0.31	1	-0.39	9	10
FOXO3	-0.032	0.12	0.28	1	-0.35	9	10
AKT1	-0.033	0.13	0.29	1	-0.37	9	10
BAD	-0.032	0.12	0.28	1	-0.35	9	10
megakaryocyte differentiation	-0.027	0.13	0.31	1	-0.37	9	10
GSK3B	-0.032	0.12	0.28	1	-0.35	9	10
RAF1	-0.025	0.12	0.24	1	-0.29	9	10
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	-0.032	0.13	0.31	1	-0.39	9	10
STAT1	-0.086	0.3	0.41	1	-0.9	9	10
HRAS/SPRED1	-0.028	0.11	0.24	1	-0.29	9	10
cell proliferation	-0.032	0.13	0.31	1	-0.39	9	10
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
TEC	0.01	0.001	-10000	0	-10000	0	0
RPS6KB1	-0.035	0.14	0.31	1	-0.4	9	10
HRAS/SPRED2	-0.028	0.11	0.24	1	-0.29	9	10
LYN/TEC/p62DOK	-0.022	0.14	0.28	1	-0.37	9	10
MAPK3	-0.017	0.087	0.21	1	-0.22	8	9
STAP1	-0.03	0.14	0.31	1	-0.39	9	10
GRAP2	0.008	0.004	-10000	0	-10000	0	0
JAK2	-0.083	0.27	0.4	1	-0.79	9	10
STAT1 (dimer)	-0.083	0.3	0.41	1	-0.88	9	10
mol:Gleevec	0.001	0.006	0.015	8	-0.023	1	9
GRB2/SOCS1/VAV1	-0.029	0.14	0.28	1	-0.36	10	11
actin filament polymerization	-0.032	0.13	0.31	1	-0.38	9	10
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.055	0.2	0.34	1	-0.57	9	10
PIK3R1	0.01	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.025	0.12	0.27	1	-0.35	9	10
PI3K	-0.029	0.14	0.28	1	-0.38	9	10
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.09	0.33	-10000	0	-1	9	9
MAPK8	-0.033	0.14	0.31	1	-0.4	9	10
STAT3 (dimer)	-0.032	0.13	0.31	1	-0.38	9	10
positive regulation of transcription	-0.012	0.075	0.19	1	-0.18	8	9
mol:GDP	-0.04	0.13	0.27	1	-0.36	9	10
PIK3C2B	-0.032	0.13	0.31	1	-0.39	9	10
CBL/CRKL	-0.03	0.13	0.28	1	-0.36	9	10
FER	-0.034	0.14	0.31	1	-0.41	9	10
SH2B3	-0.032	0.13	0.31	1	-0.39	9	10
PDPK1	-0.033	0.12	0.27	1	-0.33	9	10
SNAI2	-0.033	0.14	0.31	1	-0.4	9	10
positive regulation of cell proliferation	-0.064	0.24	0.38	1	-0.69	9	10
KITLG	0.008	0.015	0.062	1	-0.036	6	7
cell motility	-0.064	0.24	0.38	1	-0.69	9	10
PTPN6	0.009	0.011	0.031	7	-0.033	1	8
EPOR	-0.012	0.097	-10000	0	-10000	0	0
STAT5A (dimer)	-0.052	0.2	0.36	1	-0.58	9	10
SOCS1	0.01	0.001	-10000	0	-10000	0	0
cell migration	0.017	0.14	0.38	9	-0.31	1	10
SOS1	0.01	0.001	-10000	0	-10000	0	0
EPO	0.006	0.011	-10000	0	-0.02	8	8
VAV1	0.009	0.004	-10000	0	-10000	0	0
GRB10	-0.033	0.14	0.31	1	-0.4	9	10
PTPN11	0.009	0.009	-10000	0	-0.027	1	1
SCF/KIT	-0.032	0.14	0.33	1	-0.41	9	10
GO:0007205	0.001	0.008	0.021	9	-0.028	1	10
MAP2K1	-0.02	0.095	0.22	1	-0.23	9	10
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.099	0.35	0.52	1	-1.1	9	10
MAP2K2	-0.02	0.095	0.22	1	-0.23	9	10
SHC/Grb2/SOS1	-0.023	0.14	0.28	1	-0.38	9	10
STAT5A	-0.054	0.2	0.36	1	-0.59	9	10
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	-0.033	0.13	0.31	1	-0.39	9	10
SHC/GRAP2	0.002	0.039	-10000	0	-0.12	7	7
PTPRO	-0.03	0.13	0.31	1	-0.38	9	10
SH2B2	-0.032	0.13	0.31	1	-0.39	9	10
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	-0.031	0.14	0.31	1	-0.39	9	10
CREBBP	0.004	0.046	0.25	1	-10000	0	1
BCL2	-0.011	0.095	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	-0.004	0.003	-10000	0	-10000	0	0
RAS family/GTP	0.038	0.091	0.22	12	-0.13	3	15
NFATC4	-0.005	0.033	0.13	2	-0.1	3	5
ERBB2IP	0.008	0.007	-10000	0	-0.009	12	12
HSP90 (dimer)	0.01	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.015	0.059	0.13	11	-0.12	3	14
JUN	0.019	0.13	0.3	10	-0.25	4	14
HRAS	0.01	0.006	0.026	1	-0.009	6	7
DOCK7	-0.005	0.045	0.17	2	-0.12	4	6
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.015	0.028	0.1	1	-0.094	3	4
AKT1	-0.002	0.003	0.007	3	-10000	0	3
BAD	-0.004	0.002	-10000	0	-10000	0	0
MAPK10	-0.006	0.022	0.11	1	-0.085	1	2
mol:GTP	0.001	0.003	0.007	11	-0.005	6	17
ErbB2/ErbB3/neuregulin 1 beta	0.016	0.064	0.14	11	-0.12	3	14
RAF1	0.035	0.12	0.29	12	-10000	0	12
ErbB2/ErbB3/neuregulin 2	0.002	0.036	0.057	1	-0.095	9	10
STAT3	0.013	0.004	-10000	0	-10000	0	0
cell migration	-0.007	0.044	0.15	2	-0.099	2	4
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	0.032	0.26	0.5	12	-0.61	6	18
FOS	0.034	0.23	0.47	12	-0.38	9	21
NRAS	0.01	0.006	0.026	1	-0.009	6	7
mol:Ca2+	0.015	0.059	0.13	11	-0.12	3	14
MAPK3	0.038	0.22	0.45	12	-0.46	6	18
MAPK1	0.038	0.22	0.45	12	-0.46	6	18
JAK2	-0.004	0.042	0.17	2	-0.12	3	5
NF2	0.004	0.004	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.006	0.019	0.082	1	-0.11	1	2
NRG1	0.008	0.008	0.033	1	-0.008	8	9
GRB2/SOS1	0.014	0.016	-10000	0	-0.12	1	1
MAPK8	-0.006	0.065	0.2	2	-0.18	6	8
MAPK9	-0.006	0.029	0.1	2	-0.085	1	3
ERBB2	-0.007	0.007	-10000	0	-10000	0	0
ERBB3	0.01	0.007	0.033	1	-0.009	5	6
SHC1	0.01	0.006	0.027	1	-0.008	6	7
RAC1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.004	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.013	0.004	-10000	0	-10000	0	0
RNF41	-0.006	0.004	-10000	0	-10000	0	0
FRAP1	-0.002	0.002	0.005	2	-10000	0	2
RAC1-CDC42/GTP	-0.012	0.026	0.073	1	-0.097	4	5
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.009	-10000	0	-10000	0	0
CHRNA1	0.039	0.25	0.51	12	-0.54	6	18
myelination	-0.019	0.039	0.12	2	-10000	0	2
PPP3CB	-0.006	0.039	0.16	2	-0.11	3	5
KRAS	0.01	0.006	0.026	1	-0.009	6	7
RAC1-CDC42/GDP	0.014	0.038	-10000	0	-0.13	4	4
NRG2	0.01	0.002	-10000	0	-10000	0	0
mol:GDP	0.006	0.019	0.082	1	-0.11	1	2
SOS1	0.011	0.003	0.023	1	-10000	0	1
MAP2K2	0.029	0.14	0.32	12	-0.18	5	17
SRC	0.01	0	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	-0.006	0.039	0.15	2	-0.12	3	5
MAP2K1	0.038	0.2	0.42	12	-0.37	5	17
heart morphogenesis	0.015	0.059	0.13	11	-0.12	3	14
RAS family/GDP	0.028	0.063	0.14	12	-0.13	3	15
GRB2	0.011	0.002	0.023	1	-10000	0	1
PRKACA	0.006	0.004	-10000	0	-10000	0	0
CHRNE	0.009	0.062	0.3	2	-0.13	4	6
HSP90AA1	0.01	0	-10000	0	-10000	0	0
activation of caspase activity	0.002	0.003	-10000	0	-0.007	3	3
nervous system development	0.015	0.059	0.13	11	-0.12	3	14
CDC42	0.01	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.019	0.095	0.18	8	-0.22	3	11
ACTA1	0.013	0.11	0.16	16	-0.19	10	26
NUMA1	0.019	0.095	0.21	5	-0.26	2	7
SPTAN1	0.01	0.11	0.2	6	-0.19	10	16
LIMK1	0.01	0.11	0.22	5	-0.19	10	15
BIRC3	0.007	0.005	-10000	0	-10000	0	0
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	0.06	0.12	0.25	20	-10000	0	20
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0.001	-10000	0	-10000	0	0
PTK2	0.019	0.095	0.23	4	-0.37	1	5
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.011	0.11	0.15	14	-0.19	10	24
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
GSN	0.01	0.11	0.22	5	-0.19	10	15
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	0.012	0.076	-10000	0	-0.59	1	1
BID	0	0	-10000	0	-10000	0	0
MAP3K1	0.014	0.05	0.14	2	-0.16	1	3
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.01	0.026	-10000	0	-0.12	3	3
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.012	0.11	0.16	15	-0.19	10	25
CASP9	0.01	0.001	-10000	0	-10000	0	0
DNA repair	-0.01	0.046	-10000	0	-0.11	1	1
neuron apoptosis	0.013	0.019	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.014	0.1	0.23	4	-0.19	8	12
APAF1	0.01	0.002	-10000	0	-10000	0	0
CASP6	0.019	0.069	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.007	0.1	0.2	5	-0.18	10	15
CASP7	-0.008	0.1	0.17	9	-0.23	10	19
KRT18	-0.005	0.12	-10000	0	-0.49	4	4
apoptosis	0.013	0.092	0.21	4	-0.36	1	5
DFFA	0.01	0.11	0.15	15	-0.19	10	25
DFFB	0.009	0.11	0.22	5	-0.19	10	15
PARP1	0.01	0.046	0.11	1	-10000	0	1
actin filament polymerization	-0.008	0.1	0.18	10	-0.22	4	14
TNF	0.007	0.005	-10000	0	-10000	0	0
CYCS	0.024	0.086	0.2	11	-0.16	2	13
SATB1	0.014	0.073	-10000	0	-10000	0	0
SLK	0.01	0.11	0.22	5	-0.19	10	15
p15 BID/BAX	0.02	0.074	0.12	20	-0.095	13	33
CASP2	-0.003	0.043	-10000	0	-10000	0	0
JNK cascade	-0.014	0.05	0.16	1	-0.14	2	3
CASP3	0.014	0.12	0.16	19	-0.2	10	29
LMNB2	0.015	0.051	0.18	1	-10000	0	1
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0.001	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.009	0.038	-10000	0	-0.093	9	9
negative regulation of DNA binding	0.012	0.075	-10000	0	-0.58	1	1
stress fiber formation	0.011	0.11	0.22	5	-0.19	10	15
GZMB	-0.003	0.003	-10000	0	-10000	0	0
CASP1	0.004	0.002	-10000	0	0	12	12
LMNB1	0.009	0.066	0.18	1	-0.26	2	3
APP	0.013	0.02	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.002	0.003	7	-10000	0	7
VIM	0.015	0.091	0.21	4	-0.35	1	5
LMNA	0.015	0.051	0.15	4	-10000	0	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.001	0.046	-10000	0	-0.13	1	1
LRDD	0.01	0	-10000	0	-10000	0	0
SREBF1	0.01	0.11	0.22	5	-0.19	10	15
APAF-1/Caspase 9	0.013	0.051	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.019	0.095	0.21	5	-0.25	2	7
CFL2	0.008	0.1	0.22	4	-0.18	10	14
GAS2	0.01	0.11	0.18	8	-0.19	10	18
positive regulation of apoptosis	0.014	0.054	0.16	4	-10000	0	4
PRF1	0.008	0.004	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 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
EP300	0.009	0.024	0.046	14	-0.032	14	28
HSPA8	0.007	0.011	-10000	0	-0.015	15	15
SMAD3/SMAD4/ER alpha	-0.014	0.07	0.14	4	-0.16	9	13
AKT1	0.006	0.018	-10000	0	-0.077	3	3
GSC	-0.084	0.45	0.5	11	-1.1	11	22
NKX2-5	0.001	0.006	-10000	0	-0.039	1	1
muscle cell differentiation	0.009	0.064	0.22	2	-10000	0	2
SMAD2-3/SMAD4/SP1	-0.014	0.09	0.21	1	-0.22	6	7
SMAD4	-0.009	0.058	0.12	4	-0.18	3	7
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.008	0.007	-10000	0	-0.008	12	12
Cbp/p300/MSG1	0.011	0.053	0.084	13	-0.11	8	21
SMAD3/SMAD4/VDR	0.015	0.048	-10000	0	-0.11	2	2
MYC	0.012	0.014	0.081	3	-10000	0	3
CDKN2B	-0.038	0.22	-10000	0	-1.1	3	3
AP1	0.001	0.07	0.16	3	-0.27	2	5
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.048	-10000	0	-0.21	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.003	0.066	-10000	0	-0.3	3	3
SP3	0.01	0.001	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	0	0.047	0.065	11	-0.1	12	23
SMAD3/SMAD4/GR	-0.009	0.052	-10000	0	-0.15	5	5
GATA3	0.01	0.013	0.12	1	-10000	0	1
SKI/SIN3/HDAC complex/NCoR1	0.004	0.027	-10000	0	-0.14	1	1
MEF2C/TIF2	-0.021	0.098	-10000	0	-0.22	12	12
endothelial cell migration	0.022	0.27	1.1	4	-0.49	4	8
MAX	0.007	0.025	0.057	4	-0.09	4	8
RBBP7	0.008	0.007	-10000	0	-0.008	12	12
RBBP4	0.008	0.007	-10000	0	-0.008	12	12
RUNX2	0.009	0.003	-10000	0	-10000	0	0
RUNX3	0.007	0.005	-10000	0	-10000	0	0
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.007	0.025	0.057	4	-0.09	4	8
VDR	0.009	0.003	-10000	0	-10000	0	0
CDKN1A	-0.076	0.31	-10000	0	-1	7	7
KAT2B	0.006	0.013	0.028	1	-0.019	14	15
SMAD2/SMAD2/SMAD4/FOXH1	0.004	0.13	0.22	11	-0.27	11	22
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.008	0.007	-10000	0	-0.008	12	12
SERPINE1	-0.023	0.27	0.49	4	-1.1	4	8
SMAD3/SMAD4/ATF2	-0.01	0.049	-10000	0	-0.14	5	5
SMAD3/SMAD4/ATF3	-0.007	0.049	-10000	0	-0.2	2	2
SAP30	0.007	0.007	-10000	0	-0.008	12	12
Cbp/p300/PIAS3	0.025	0.049	0.11	14	-10000	0	14
JUN	-0.007	0.071	0.17	3	-0.27	2	5
SMAD3/SMAD4/IRF7	-0.007	0.044	-10000	0	-0.15	2	2
TFE3	0.011	0.024	0.073	5	-0.067	4	9
COL1A2	0.004	0.2	0.4	8	-0.59	5	13
mesenchymal cell differentiation	0.01	0.047	0.14	3	-10000	0	3
DLX1	0.009	0.004	-10000	0	-10000	0	0
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	0.006	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/Max	-0.009	0.052	-10000	0	-0.15	5	5
Cbp/p300/SNIP1	0.018	0.024	0.069	1	-10000	0	1
ZBTB17	0.012	0.011	0.066	3	-10000	0	3
LAMC1	-0.003	0.057	0.17	4	-0.16	1	5
TGIF2/HDAC complex/SMAD3/SMAD4	-0.006	0.043	-10000	0	-0.15	2	2
IRF7	0.01	0.002	-10000	0	-10000	0	0
ESR1	0.005	0.024	0.085	4	-0.039	10	14
HNF4A	0.003	0.005	-10000	0	-10000	0	0
MEF2C	-0.018	0.096	-10000	0	-0.22	12	12
SMAD2-3/SMAD4	-0.01	0.072	-10000	0	-0.22	3	3
Cbp/p300/Src-1	0.021	0.033	0.084	4	-10000	0	4
IGHV3OR16-13	-0.005	0.013	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.008	0.018	0.034	14	-0.025	14	28
SKIL	0.01	0.002	-10000	0	-10000	0	0
HDAC1	0.008	0.007	-10000	0	-0.008	12	12
HDAC2	0.008	0.007	-10000	0	-0.008	12	12
SNIP1	0.007	0.009	-10000	0	-0.012	15	15
GCN5L2	0.002	0.014	0.028	14	-0.02	13	27
SMAD3/SMAD4/TFE3	0.003	0.054	-10000	0	-0.18	1	1
MSG1/HSC70	-0.002	0.042	-10000	0	-0.12	8	8
SMAD2	-0.002	0.051	0.067	9	-0.11	13	22
SMAD3	-0.002	0.045	0.12	4	-0.11	6	10
SMAD3/E2F4-5/DP1/p107/SMAD4	-0.002	0.07	0.14	3	-0.27	3	6
SMAD2/SMAD2/SMAD4	-0.003	0.05	-10000	0	-0.2	3	3
NCOR1	0.008	0.007	-10000	0	-0.008	12	12
NCOA2	0.009	0.003	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	0.01	0.004	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.008	0.1	0.2	1	-0.25	3	4
IFNB1	-0.005	0.057	0.16	6	-0.16	1	7
SMAD3/SMAD4/MEF2C	-0.01	0.098	-10000	0	-0.2	12	12
CITED1	0.009	0.003	-10000	0	-10000	0	0
SMAD2-3/SMAD4/ARC105	-0.004	0.067	-10000	0	-0.19	3	3
RBL1	0.01	0.002	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.016	0.099	-10000	0	-0.48	3	3
RUNX1-3/PEBPB2	0	0.043	-10000	0	-0.1	12	12
SMAD7	-0.009	0.099	-10000	0	-0.48	1	1
MYC/MIZ-1	0.019	0.025	0.14	3	-10000	0	3
SMAD3/SMAD4	-0.003	0.16	0.25	12	-0.3	14	26
IL10	-0.004	0.059	-10000	0	-0.17	1	1
PIASy/HDAC complex	0.006	0.02	0.032	7	-0.032	15	22
PIAS3	0.008	0.012	0.024	4	-0.017	14	18
CDK2	0.009	0.017	0.034	14	-0.023	14	28
IL5	-0.015	0.051	0.27	1	-0.17	1	2
CDK4	0.009	0.019	0.038	14	-0.024	14	28
PIAS4	0.006	0.02	0.032	7	-0.032	15	22
ATF3	0.01	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	-0.019	0.072	-10000	0	-0.21	7	7
FOXG1	0.005	0.007	0.03	1	-10000	0	1
FOXO3	-0.009	0.017	-10000	0	-0.096	3	3
FOXO1	-0.009	0.017	-10000	0	-0.094	3	3
FOXO4	-0.009	0.017	-10000	0	-0.094	3	3
heart looping	-0.018	0.095	-10000	0	-0.22	12	12
CEBPB	0.008	0.011	-10000	0	-0.046	3	3
SMAD3/SMAD4/DLX1	-0.012	0.051	-10000	0	-0.14	6	6
MYOD1	0.003	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.007	0.041	-10000	0	-0.15	2	2
SMAD3/SMAD4/GATA3	-0.009	0.05	-10000	0	-0.16	4	4
SnoN/SIN3/HDAC complex/NCoR1	0.01	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.006	0.052	-10000	0	-0.14	5	5
SMAD3/SMAD4/SP1-3	-0.008	0.07	-10000	0	-0.19	7	7
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.004	0.053	0.1	10	-0.096	12	22
SIN3B	0.008	0.007	-10000	0	-0.008	12	12
SIN3A	0.008	0.007	-10000	0	-0.008	12	12
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.01	0.12	0.21	11	-0.24	11	22
ITGB5	-0.007	0.086	0.2	4	-0.18	6	10
TGIF/SIN3/HDAC complex/CtBP	0.004	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.011	0.048	-10000	0	-0.14	5	5
AR	0.008	0.004	-10000	0	-10000	0	0
negative regulation of cell growth	0	0.073	-10000	0	-0.34	2	2
SMAD3/SMAD4/MYOD	-0.008	0.041	-10000	0	-0.15	2	2
E2F5	0.01	0.002	-10000	0	-10000	0	0
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.021	0.1	0.19	11	-0.19	11	22
SMAD2-3/SMAD4/FOXO1-3a-4	-0.013	0.078	-10000	0	-0.3	4	4
TFDP1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.002	0.066	-10000	0	-0.27	2	2
SMAD3/SMAD4/RUNX2	-0.01	0.047	-10000	0	-0.14	3	3
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0.002	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.005	0.053	-10000	0	-0.1	17	17
MAP4K1	0.009	0.003	-10000	0	-10000	0	0
MAP3K8	0.01	0.002	-10000	0	-10000	0	0
PRKCB	0.009	0.004	-10000	0	-10000	0	0
DBNL	0.01	0	-10000	0	-10000	0	0
CRKL	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.024	0.069	-10000	0	-0.15	17	17
JUN	-0.035	0.17	-10000	0	-0.52	8	8
MAP3K7	-0.023	0.072	-10000	0	-0.15	16	16
GRAP2	0.008	0.004	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
MAP2K4	-0.004	0.12	0.31	5	-0.19	10	15
LAT	0.009	0.004	-10000	0	-10000	0	0
LCP2	0.009	0.003	-10000	0	-10000	0	0
MAPK8	-0.035	0.17	0.21	1	-0.53	8	9
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.023	0.074	-10000	0	-0.15	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.002	0.052	-10000	0	-0.097	17	17

×

Calcium signaling in the CD4+ TCR 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
NFATC1	0.058	0.17	0.36	15	-10000	0	15
NFATC2	0.024	0.1	0.36	6	-10000	0	6
NFATC3	0.058	0.17	0.45	11	-10000	0	11
CD40LG	0.036	0.27	0.68	10	-10000	0	10
PTGS2	0.082	0.38	0.86	13	-0.33	4	17
JUNB	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.011	-10000	0	-10000	0	0
CaM/Ca2+	0.001	0.011	-10000	0	-10000	0	0
CALM1	0.027	0.058	0.12	15	-10000	0	15
JUN	0.017	0.038	0.09	12	-10000	0	12
mol:Ca2+	-0.003	0.005	-10000	0	-0.017	5	5
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.008	-10000	0	-10000	0	0
FOSL1	0.009	0.003	-10000	0	-10000	0	0
CREM	0.01	0.003	-10000	0	-0.009	2	2
Jun/NFAT1-c-4/p21SNFT	-0.032	0.058	-10000	0	-0.16	8	8
FOS	0.017	0.038	0.11	9	-10000	0	9
IFNG	-0.005	0.18	0.5	7	-10000	0	7
AP-1/NFAT1-c-4	-0.029	0.096	-10000	0	-0.26	9	9
FASLG	-0.036	0.13	0.38	4	-0.33	4	8
NFAT1-c-4/ICER1	-0.016	0.056	0.21	3	-10000	0	3
IL2RA	-0.001	0.22	0.6	7	-0.32	4	11
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSF2	0.099	0.37	0.79	15	-10000	0	15
JunB/Fra1/NFAT1-c-4	-0.011	0.066	0.2	3	-0.15	5	8
IL4	0.098	0.37	0.79	15	-10000	0	15
IL2	-0.003	0.005	-10000	0	-10000	0	0
IL3	-0.002	0.012	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
BATF3	0.009	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.01	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	-0.002	0.048	-10000	0	-0.096	15	15
ER alpha/Gai/GDP/Gbeta gamma	-0.028	0.1	-10000	0	-0.24	14	14
AKT1	-0.086	0.24	-10000	0	-0.61	13	13
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.085	0.24	-10000	0	-0.62	13	13
mol:Ca2+	0.005	0.074	0.18	2	-0.25	3	5
IGF1R	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.008	0.044	-10000	0	-0.1	15	15
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.082	0.23	0.59	13	-10000	0	13
RhoA/GTP	-0.004	0.032	-10000	0	-0.08	12	12
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.033	0.1	-10000	0	-0.24	14	14
regulation of stress fiber formation	0.013	0.037	-10000	0	-0.1	5	5
E2/ERA-ERB (dimer)	-0.01	0.048	-10000	0	-0.11	15	15
KRAS	0.01	0.001	-10000	0	-10000	0	0
G13/GTP	-0.002	0.035	-10000	0	-0.089	11	11
pseudopodium formation	-0.013	0.037	0.1	5	-10000	0	5
E2/ER alpha (dimer)/PELP1	-0.003	0.039	-10000	0	-0.1	11	11
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.01	0.002	-10000	0	-10000	0	0
GNAO1	0.009	0.003	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.047	0.14	0.17	1	-0.36	12	13
E2/ER beta (dimer)	-0.002	0.034	-10000	0	-0.12	6	6
mol:GDP	-0.035	0.09	-10000	0	-0.22	15	15
mol:NADP	-0.047	0.14	0.17	1	-0.36	12	13
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.002	0.069	-10000	0	-0.26	3	3
IGF-1R heterotetramer	0.01	0	-10000	0	-10000	0	0
PLCB1	-0.014	0.056	-10000	0	-0.27	3	3
PLCB2	-0.014	0.056	-10000	0	-0.27	3	3
IGF1	0.009	0.003	-10000	0	-10000	0	0
mol:L-citrulline	-0.047	0.14	0.17	1	-0.36	12	13
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.013	0.11	-10000	0	-0.56	3	3
JNK cascade	-0.002	0.034	-10000	0	-0.12	6	6
BCAR1	0.01	0	-10000	0	-10000	0	0
ESR2	0.009	0.003	-10000	0	-10000	0	0
GNAQ	0.01	0	-10000	0	-10000	0	0
ESR1	0.008	0.004	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	-0.001	0.046	-10000	0	-0.33	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.014	0.065	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.033	0.1	-10000	0	-0.24	14	14
GNAZ	0.01	0.002	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.011	0.044	-10000	0	-0.12	11	11
STRN	0.01	0.002	-10000	0	-10000	0	0
GNAL	0.008	0.004	-10000	0	-10000	0	0
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	-0.011	0.025	-10000	0	-0.1	6	6
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.01	0.002	-10000	0	-10000	0	0
HBEGF	-0.023	0.11	0.17	2	-0.22	14	16
cAMP biosynthetic process	-0.02	0.044	-10000	0	-0.082	26	26
SRC	-0.026	0.1	0.15	2	-0.23	14	16
PI3K	0.012	0.022	-10000	0	-0.12	2	2
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.022	0.084	-10000	0	-0.2	14	14
SOS1	0.01	0.001	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.033	0.085	-10000	0	-0.21	14	14
Gs family/GTP	-0.019	0.046	-10000	0	-0.083	26	26
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.019	0.012	-10000	0	-0.091	1	1
vasodilation	-0.045	0.14	0.17	1	-0.35	12	13
mol:DAG	-0.002	0.069	-10000	0	-0.26	3	3
Gs family/GDP/Gbeta gamma	-0.041	0.081	-10000	0	-0.2	14	14
MSN	-0.013	0.038	0.11	5	-10000	0	5
Gq family/GTP	-0.011	0.06	-10000	0	-0.28	3	3
mol:PI-3-4-5-P3	-0.082	0.23	-10000	0	-0.6	13	13
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.045	0.14	0.35	12	-0.17	1	13
GRB2/SOS1	0.014	0.015	-10000	0	-0.12	1	1
RhoA/GDP	-0.03	0.088	-10000	0	-0.21	15	15
NOS3	-0.05	0.15	0.17	1	-0.37	12	13
GNA11	0.01	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.062	0.17	-10000	0	-0.4	15	15
E2/ER alpha (dimer)/PELP1/Src	-0.035	0.1	-10000	0	-0.24	14	14
ruffle organization	-0.013	0.037	0.1	5	-10000	0	5
ROCK2	-0.013	0.04	0.11	5	-10000	0	5
GNA14	0.009	0.003	-10000	0	-10000	0	0
GNA15	0.01	0.001	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.014	0.1	-10000	0	-0.22	13	13
MMP2	-0.026	0.11	0.21	1	-0.23	17	18

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.063	0.28	0.54	1	-0.7	10	11
NCK1/PAK1/Dok-R	-0.059	0.12	-10000	0	-0.35	10	10
NCK1/Dok-R	-0.057	0.26	-10000	0	-0.91	6	6
PIK3CA	0.01	0.003	-10000	0	-0.007	1	1
mol:beta2-estradiol	0.005	0.071	0.22	6	-0.15	5	11
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.008	0.007	-10000	0	-0.008	10	10
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	0.005	0.075	0.22	6	-0.14	7	13
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.04	0.24	-10000	0	-0.85	6	6
FN1	0.009	0.003	-10000	0	-10000	0	0
PLD2	-0.045	0.28	0.52	2	-0.92	6	8
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	0.005	0.005	-10000	0	-10000	0	0
ELK1	-0.041	0.25	0.48	2	-0.84	6	8
GRB7	0.007	0.005	-10000	0	-10000	0	0
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.059	0.25	-10000	0	-0.88	6	6
CDKN1A	-0.077	0.28	0.46	3	-0.6	16	19
ITGA5	0.01	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.057	0.26	-10000	0	-0.91	6	6
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.044	0.22	0.45	2	-0.54	10	12
PLG	-0.043	0.28	0.52	2	-0.92	6	8
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.051	0.26	0.52	1	-0.75	7	8
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.008	-10000	0	-0.008	15	15
ANGPT2	-0.049	0.26	0.5	2	-0.79	6	8
BMX	-0.039	0.28	0.52	2	-0.92	6	8
ANGPT1	-0.045	0.29	0.41	5	-1	6	11
tube development	-0.058	0.26	0.47	3	-0.61	10	13
ANGPT4	0.004	0.009	0.03	2	-0.02	4	6
response to hypoxia	-0.004	0.021	0.062	2	-0.063	6	8
Tie2/Ang1/GRB14	-0.049	0.27	0.38	1	-0.94	6	7
alpha5/beta1 Integrin	0.007	0.034	-10000	0	-0.12	5	5
FGF2	0.008	0.009	0.026	3	-0.026	3	6
STAT5A (dimer)	-0.078	0.3	0.47	3	-0.64	16	19
mol:L-citrulline	-0.044	0.22	0.45	2	-0.54	10	12
AGTR1	0.005	0.014	0.061	2	-0.034	4	6
MAPK14	-0.046	0.28	0.6	1	-0.91	6	7
Tie2/SHP2	-0.016	0.15	-10000	0	-0.72	2	2
TEK	-0.014	0.18	0.57	2	-1.3	1	3
RPS6KB1	-0.055	0.26	0.54	1	-0.75	7	8
Angiotensin II/AT1	0.005	0.025	0.14	2	-0.05	4	6
Tie2/Ang1/GRB2	-0.049	0.28	0.38	1	-0.94	6	7
MAPK3	-0.043	0.26	0.48	2	-0.86	6	8
MAPK1	-0.043	0.26	0.48	2	-0.86	6	8
Tie2/Ang1/GRB7	-0.047	0.27	0.38	1	-0.92	6	7
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.043	0.28	0.52	2	-0.92	6	8
PI3K	-0.065	0.3	0.56	1	-0.88	7	8
FES	-0.046	0.28	0.59	1	-0.9	6	7
Crk/Dok-R	-0.056	0.26	-10000	0	-0.91	6	6
Tie2/Ang1/ABIN2	-0.049	0.28	0.38	1	-0.94	6	7
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.055	0.26	0.44	3	-0.63	10	13
STAT5A	0.009	0.005	-10000	0	-0.01	6	6
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.055	0.26	0.54	1	-0.75	7	8
Tie2/Ang2	-0.084	0.33	0.5	3	-0.82	10	13
Tie2/Ang1	-0.045	0.3	0.57	2	-0.98	6	8
FOXO1	-0.064	0.27	0.46	3	-0.68	10	13
ELF1	0.01	0.035	0.19	2	-0.11	1	3
ELF2	-0.038	0.28	0.55	2	-0.92	6	8
mol:Choline	-0.042	0.27	0.52	2	-0.88	6	8
cell migration	-0.033	0.068	-10000	0	-0.19	10	10
FYN	-0.07	0.28	0.48	3	-0.7	10	13
DOK2	0.009	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.066	0.26	0.46	3	-0.55	16	19
ETS1	0.003	0.075	0.16	5	-0.22	6	11
PXN	-0.045	0.23	0.51	1	-0.63	7	8
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.052	0.24	0.45	2	-0.6	10	12
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	0.001	0.076	0.17	5	-0.22	6	11
MAPKKK cascade	-0.042	0.27	0.52	2	-0.88	6	8
RASA1	0.01	0.001	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.049	0.28	0.38	1	-0.95	6	7
NCK1	0.01	0.001	-10000	0	-10000	0	0
vasculogenesis	-0.037	0.2	0.4	3	-0.48	10	13
mol:Phosphatidic acid	-0.042	0.27	0.52	2	-0.88	6	8
mol:Angiotensin II	0	0.011	0.056	2	-0.031	4	6
mol:NADP	-0.044	0.22	0.45	2	-0.54	10	12
Rac1/GTP	-0.077	0.22	-10000	0	-0.7	7	7
MMP2	-0.038	0.28	0.52	2	-0.9	6	8

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.01	0.13	-10000	0	-0.33	9	9
MAP3K8	0.009	0.007	0.031	2	-0.012	6	8
FOS	0	0.13	0.33	2	-0.4	5	7
PRKCA	0.009	0.011	0.06	2	-0.017	6	8
PTPN7	0.008	0.017	0.096	2	-0.023	5	7
HRAS	0.009	0.004	0.018	2	-0.009	4	6
PRKCB	0.009	0.01	0.06	2	-0.016	4	6
NRAS	0.009	0.004	0.018	2	-0.009	4	6
RAS family/GTP	0.017	0.019	0.09	2	-0.091	1	3
MAPK3	0.001	0.12	0.22	2	-0.43	4	6
MAP2K1	-0.001	0.081	0.18	2	-0.29	4	6
ELK1	0.009	0.01	0.038	2	-0.024	6	8
BRAF	-0.007	0.065	-10000	0	-0.27	4	4
mol:GTP	0	0.002	0.008	2	-0.004	6	8
MAPK1	0.001	0.12	0.22	2	-0.43	4	6
RAF1	-0.007	0.065	-10000	0	-0.27	4	4
KRAS	0.009	0.004	0.018	2	-0.009	4	6

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.009	0.047	-10000	0	-0.13	10	10
EPHB2	0.009	0.003	-10000	0	-10000	0	0
Syndecan-2/TACI	-0.009	0.034	-10000	0	-0.098	10	10
LAMA1	0.008	0.004	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.001	0.049	-10000	0	-0.11	11	11
HRAS	0.01	0	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.01	0.033	-10000	0	-0.098	10	10
ITGA5	0.01	0.002	-10000	0	-10000	0	0
BAX	0.025	0.055	-10000	0	-10000	0	0
EPB41	0.01	0	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.004	0.032	-10000	0	-0.088	10	10
LAMA3	0.01	0.002	-10000	0	-10000	0	0
EZR	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.01	0.001	-10000	0	-10000	0	0
Syndecan-2/MMP2	-0.012	0.053	-10000	0	-0.14	10	10
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.009	0.027	-10000	0	-0.12	3	3
dendrite morphogenesis	-0.007	0.04	-10000	0	-0.11	10	10
Syndecan-2/GM-CSF	-0.01	0.033	-10000	0	-0.098	10	10
determination of left/right symmetry	0.003	0.002	-10000	0	-10000	0	0
Syndecan-2/PKC delta	-0.005	0.036	-10000	0	-0.1	10	10
GNB2L1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.009	0.064	0.14	13	-0.088	10	23
MAPK1	0.009	0.064	0.14	13	-0.088	10	23
Syndecan-2/RACK1	0.001	0.032	-10000	0	-0.084	10	10
NF1	0.01	0	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.003	0.002	-10000	0	-10000	0	0
ITGA2	0.009	0.004	-10000	0	-10000	0	0
MAPK8	0.025	0.061	0.16	13	-10000	0	13
Syndecan-2/alpha2/beta1 Integrin	-0.009	0.058	-10000	0	-0.12	15	15
Syndecan-2/Kininogen	-0.01	0.033	-10000	0	-0.098	10	10
ITGB1	0.01	0	-10000	0	-10000	0	0
SRC	0.006	0.059	0.13	13	-10000	0	13
Syndecan-2/CASK/Protein 4.1	-0.004	0.032	-10000	0	-0.089	10	10
extracellular matrix organization	-0.006	0.036	-10000	0	-0.1	10	10
actin cytoskeleton reorganization	-0.009	0.047	-10000	0	-0.13	10	10
Syndecan-2/Caveolin-2/Ras	-0.001	0.036	-10000	0	-0.09	11	11
Syndecan-2/Laminin alpha3	-0.008	0.044	-10000	0	-0.12	10	10
Syndecan-2/RasGAP	0.003	0.037	-10000	0	-0.089	10	10
alpha5/beta1 Integrin	0.007	0.034	-10000	0	-0.12	5	5
PRKCD	0.01	0	-10000	0	-10000	0	0
Syndecan-2 dimer	-0.007	0.04	-10000	0	-0.11	10	10
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.034	-10000	0	-0.15	1	1
RHOA	0.01	0	-10000	0	-10000	0	0
SDCBP	0.01	0	-10000	0	-10000	0	0
TNFRSF13B	0.003	0.005	-10000	0	-10000	0	0
RASA1	0.01	0.001	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.009	0.027	-10000	0	-0.12	3	3
Syndecan-2/Synbindin	-0.005	0.036	-10000	0	-0.1	10	10
TGFB1	0.01	0.002	-10000	0	-10000	0	0
CASP3	0.008	0.065	0.14	13	-0.09	10	23
FN1	0.009	0.003	-10000	0	-10000	0	0
Syndecan-2/IL8	-0.006	0.034	-10000	0	-0.099	9	9
SDC2	0.003	0.002	-10000	0	-10000	0	0
KNG1	0.001	0.004	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	-0.005	0.036	-10000	0	-0.1	10	10
TRAPPC4	0.01	0	-10000	0	-10000	0	0
CSF2	0.001	0.003	-10000	0	-10000	0	0
Syndecan-2/TGFB1	-0.006	0.036	-10000	0	-0.1	10	10
Syndecan-2/Syntenin/PI-4-5-P2	-0.004	0.032	-10000	0	-0.089	10	10
Syndecan-2/Ezrin	0	0.035	-10000	0	-0.09	10	10
PRKACA	0.008	0.065	0.14	13	-0.09	10	23
angiogenesis	-0.006	0.033	-10000	0	-0.099	9	9
MMP2	0.008	0.004	-10000	0	-10000	0	0
IL8	0.007	0.005	-10000	0	-10000	0	0
calcineurin-NFAT signaling pathway	-0.009	0.034	-10000	0	-0.098	10	10

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.015	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.002	0.046	-10000	0	-0.12	10	10
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.008	0.045	-10000	0	-0.1	10	10
NGF (dimer)/p75(NTR)/BEX1	-0.02	0.06	-10000	0	-0.12	20	20
NT-4/5 (dimer)/p75(NTR)	-0.001	0.038	-10000	0	-0.12	7	7
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	-0.002	0.062	0.13	11	-0.16	2	13
IKBKG	0.01	0	-10000	0	-10000	0	0
BDNF	0.008	0.004	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	-0.012	0.058	-10000	0	-0.12	17	17
FURIN	0.01	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.001	0.046	-10000	0	-0.11	11	11
LINGO1	0.009	0.004	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)	0.008	0.004	-10000	0	-10000	0	0
NTRK1	0.008	0.004	-10000	0	-10000	0	0
RTN4R	0.01	0	-10000	0	-10000	0	0
neuron apoptosis	0.009	0.1	0.24	5	-0.28	3	8
IRAK1	0.01	0	-10000	0	-10000	0	0
SHC1	0.002	0.071	0.14	12	-0.12	10	22
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
Gamma Secretase	0.031	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.005	0.046	-10000	0	-0.11	10	10
MAGEH1	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.008	0.056	-10000	0	-0.11	18	18
Mammalian IAPs/DIABLO	0.009	0.037	-10000	0	-0.093	9	9
proNGF (dimer)	0.008	0.004	-10000	0	-10000	0	0
MAGED1	0.01	0	-10000	0	-10000	0	0
APP	0.01	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.007	0.005	-10000	0	-10000	0	0
ZNF274	0.01	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.003	0.039	-10000	0	-0.1	10	10
NGF	0.008	0.004	-10000	0	-10000	0	0
cell cycle arrest	0.019	0.058	0.14	9	-0.13	2	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.014	0.062	-10000	0	-0.17	10	10
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.005	0.034	-10000	0	-0.1	7	7
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.047	-10000	0	-0.12	10	10
PSENEN	0.01	0	-10000	0	-10000	0	0
mol:ceramide	0.001	0.066	0.13	12	-0.11	10	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.006	0.071	-10000	0	-0.15	13	13
p75(NTR)/beta APP	-0.001	0.041	-10000	0	-0.12	8	8
BEX1	0.006	0.005	-10000	0	-10000	0	0
mol:GDP	-0.018	0.04	-10000	0	-0.12	10	10
NGF (dimer)	0.008	0.023	-10000	0	-0.09	4	4
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.006	0.056	-10000	0	-0.11	17	17
PIK3R1	0.01	0	-10000	0	-10000	0	0
RAC1/GTP	0	0.04	-10000	0	-0.1	10	10
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.001	0.048	-10000	0	-0.12	10	10
RHOB	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.013	0.016	-10000	0	-0.12	1	1
NT3 (dimer)	0.005	0.005	-10000	0	-10000	0	0
TP53	0.01	0.083	0.17	14	-0.16	1	15
PRDM4	0.001	0.066	0.14	12	-0.11	10	22
BDNF (dimer)	0.005	0.019	-10000	0	-0.087	3	3
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
SORT1	0.01	0	-10000	0	-10000	0	0
activation of caspase activity	0.007	0.044	-10000	0	-0.1	10	10
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.005	0.046	-10000	0	-0.11	10	10
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0.001	-10000	0	-10000	0	0
MAPK10	-0.006	0.12	0.22	9	-0.18	15	24
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	0.001	0.066	0.14	12	-0.11	10	22
APH1B	0.01	0	-10000	0	-10000	0	0
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.001	0.048	-10000	0	-0.12	10	10
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.01	0.026	-10000	0	-0.12	3	3
NT3 (dimer)/p75(NTR)	-0.009	0.049	-10000	0	-0.13	10	10
MAPK8	-0.008	0.091	0.2	5	-0.19	8	13
MAPK9	-0.002	0.09	0.2	5	-0.19	8	13
APAF1	0.01	0.002	-10000	0	-10000	0	0
NTF3	0.005	0.005	-10000	0	-10000	0	0
NTF4	0.007	0.005	-10000	0	-10000	0	0
NDN	0.009	0.003	-10000	0	-10000	0	0
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.007	0.041	-10000	0	-0.097	10	10
p75 CTF/Sortilin/TRAF6/NRIF	0.027	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.001	0.047	-10000	0	-0.12	10	10
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.008	0.043	-10000	0	-0.095	11	11
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.004	0.044	-10000	0	-0.1	11	11
PRKACB	0.01	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	0.007	0.03	-10000	0	-0.12	4	4
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.005	-10000	0	-10000	0	0
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.002	0.079	0.12	9	-0.17	10	19
BAD	-0.007	0.1	0.2	8	-0.22	8	16
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	0.008	0.004	-10000	0	-10000	0	0
CYCS	0	0.063	0.13	12	-0.1	9	21
ADAM17	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.005	0.046	-10000	0	-0.11	10	10
BCL2L11	-0.007	0.1	0.2	8	-0.22	8	16
BDNF (dimer)/p75(NTR)	-0.008	0.052	-10000	0	-0.13	11	11
PI3K	0.003	0.047	-10000	0	-0.11	11	11
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.005	0.046	-10000	0	-0.11	10	10
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0.001	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.008	0.054	-10000	0	-0.14	10	10
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.005	0.046	-10000	0	-0.11	10	10
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.002	-10000	0	-10000	0	0
PLG	0	0.002	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.003	0.072	0.12	10	-0.14	13	23
SQSTM1	0.01	0	-10000	0	-10000	0	0
NGFRAP1	0.01	0	-10000	0	-10000	0	0
CASP3	-0.006	0.099	0.19	8	-0.21	8	16
E2F1	0.01	0.002	-10000	0	-10000	0	0
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.004	0.073	-10000	0	-0.16	12	12
NGF (dimer)/TRKA	-0.002	0.041	-10000	0	-0.12	8	8
MMP7	0.003	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.008	0.045	-10000	0	-0.1	10	10
MMP3	0.003	0.004	-10000	0	-10000	0	0
APAF-1/Caspase 9	-0.03	0.04	-10000	0	-0.16	4	4

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.069	0.23	0.56	5	-10000	0	5
PCK1	0.058	0.25	0.48	8	-1.1	2	10
HNF4A	0.084	0.28	0.72	6	-0.75	1	7
KCNJ11	0.066	0.3	0.65	6	-0.7	4	10
AKT1	0.027	0.14	0.33	2	-0.43	1	3
response to starvation	0.007	0.031	0.08	5	-0.1	1	6
DLK1	0.08	0.25	0.6	6	-10000	0	6
NKX2-1	0.017	0.13	-10000	0	-10000	0	0
ACADM	0.064	0.24	0.56	5	-0.69	1	6
TAT	0.066	0.17	0.5	2	-10000	0	2
CEBPB	0.024	0.047	0.092	21	-0.053	8	29
CEBPA	0.033	0.059	0.13	21	-0.051	8	29
TTR	0.044	0.5	0.64	19	-1	11	30
PKLR	0.062	0.27	0.54	7	-0.61	3	10
APOA1	0.082	0.31	0.77	5	-1	1	6
CPT1C	0.089	0.29	0.7	8	-0.64	1	9
ALAS1	0.056	0.16	-10000	0	-10000	0	0
TFRC	0.081	0.21	0.53	6	-10000	0	6
FOXF1	0.008	0.004	-10000	0	-10000	0	0
NF1	0.012	0	-10000	0	-10000	0	0
HNF1A (dimer)	0.01	0.001	-10000	0	-10000	0	0
CPT1A	0.069	0.23	0.56	5	-10000	0	5
HMGCS1	0.069	0.23	0.56	5	-10000	0	5
NR3C1	0.011	0.001	-10000	0	-10000	0	0
CPT1B	0.066	0.24	0.56	5	-0.64	1	6
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0	-10000	0	-10000	0	0
GCK	0.068	0.27	0.63	6	-0.65	2	8
CREB1	0.015	0.045	0.17	4	-0.16	2	6
IGFBP1	0.051	0.15	0.48	1	-10000	0	1
PDX1	0.056	0.16	-10000	0	-10000	0	0
UCP2	0.072	0.27	0.59	8	-0.7	2	10
ALDOB	0.075	0.24	0.56	5	-10000	0	5
AFP	0.025	0.057	-10000	0	-10000	0	0
BDH1	0.064	0.24	0.56	5	-0.69	1	6
HADH	0.075	0.24	0.56	5	-10000	0	5
F2	0.084	0.28	0.73	5	-10000	0	5
HNF1A	0.01	0.001	-10000	0	-10000	0	0
G6PC	0.032	0.077	-10000	0	-10000	0	0
SLC2A2	0.063	0.18	0.47	1	-10000	0	1
INS	-0.001	0.002	-10000	0	-10000	0	0
FOXA1	0.03	0.059	0.18	1	-10000	0	1
FOXA3	0.03	0.068	0.26	1	-10000	0	1
FOXA2	0.1	0.3	0.71	6	-0.6	1	7
ABCC8	0.097	0.29	0.78	6	-10000	0	6
ALB	0.028	0.065	0.35	1	-10000	0	1

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.042	0.2	2	-0.11	4	6
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.01	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.001	0.049	-10000	0	-0.2	4	4
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.025	0.046	0.12	9	-0.11	4	13
antigen processing and presentation of peptide antigen via MHC class I	-0.024	0.04	-10000	0	-0.14	7	7
CaM/Ca2+	0.011	0.03	-10000	0	-0.1	4	4
RAP1A	0.01	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.004	0.04	0.23	1	-0.14	2	3
AKT1	0.019	0.11	0.28	10	-0.13	3	13
MAP2K1	0.022	0.1	0.28	10	-0.12	2	12
MAP3K11	0.023	0.1	0.29	10	-0.12	2	12
IFNGR1	0.013	0.014	0.047	10	-0.021	2	12
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.01	0.081	-10000	0	-0.28	6	6
Rap1/GTP	-0.016	0.019	-10000	0	-0.091	4	4
CRKL/C3G	0.015	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.018	0.036	0.11	2	-0.12	4	6
CEBPB	0.037	0.11	0.34	8	-10000	0	8
STAT3	0.01	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.005	0.11	-10000	0	-0.92	1	1
STAT1	-0.011	0.039	0.23	1	-0.14	2	3
CALM1	0.011	0.001	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.003	0.008	0.03	2	-0.017	3	5
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.012	0.038	0.22	1	-0.14	2	3
CEBPB/PTGES2/Cbp/p300	0.005	0.027	-10000	0	-10000	0	0
mol:Ca2+	0.011	0.035	0.17	1	-0.11	4	5
MAPK3	0.034	0.1	0.33	8	-10000	0	8
STAT1 (dimer)	-0.014	0.059	-10000	0	-0.19	6	6
MAPK1	0.034	0.1	0.33	8	-10000	0	8
JAK2	0.013	0.014	0.047	10	-0.021	2	12
PIK3R1	0.011	0.001	-10000	0	-10000	0	0
JAK1	0.013	0.015	0.047	10	-0.021	4	14
CAMK2D	0.011	0.001	-10000	0	-10000	0	0
DAPK1	0.034	0.091	0.3	6	-10000	0	6
SMAD7	0.038	0.15	0.42	9	-10000	0	9
CBL/CRKL/C3G	0.008	0.037	0.17	2	-0.12	2	4
PI3K	0.008	0.035	-10000	0	-0.11	5	5
IFNG	0.003	0.008	0.03	2	-0.017	3	5
apoptosis	0.037	0.1	0.34	7	-10000	0	7
CAMK2G	0.011	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	0.01	0	-10000	0	-10000	0	0
CAMK2A	0.009	0.004	-10000	0	-10000	0	0
CAMK2B	0.01	0.004	-10000	0	-10000	0	0
FRAP1	0.019	0.1	0.28	10	-0.12	3	13
PRKCD	0.021	0.11	0.3	10	-0.13	3	13
RAP1B	0.01	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.024	0.04	-10000	0	-0.14	7	7
PTPN2	0.01	0.002	-10000	0	-10000	0	0
EP300	0.012	0.011	0.038	10	-0.011	5	15
IRF1	-0.026	0.063	-10000	0	-0.26	5	5
STAT1 (dimer)/PIASy	-0.011	0.041	0.18	2	-0.14	2	4
SOCS1	-0.011	0.12	-10000	0	-1.1	1	1
mol:GDP	0.005	0.03	0.14	1	-0.11	2	3
CASP1	-0.007	0.06	0.2	3	-0.15	5	8
PTGES2	0.01	0	-10000	0	-10000	0	0
IRF9	0.03	0.085	0.25	10	-10000	0	10
mol:PI-3-4-5-P3	0.004	0.033	-10000	0	-0.11	5	5
RAP1/GDP	0.005	0.025	-10000	0	-0.092	4	4
CBL	0.023	0.1	0.29	10	-0.12	2	12
MAP3K1	0.023	0.1	0.29	10	-0.12	2	12
PIAS1	0.01	0	-10000	0	-10000	0	0
PIAS4	0.01	0.001	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.024	0.04	-10000	0	-0.14	7	7
PTPN11	0.026	0.11	0.3	10	-0.12	2	12
CREBBP	0.012	0.011	0.038	10	-0.011	5	15
RAPGEF1	0.01	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.015	0	-10000	0	-10000	0	0
VLDLR	0.01	0	-10000	0	-10000	0	0
CRKL	0.01	0	-10000	0	-10000	0	0
LRPAP1	0.01	0	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
ITGA3	0.01	0.002	-10000	0	-10000	0	0
RELN/VLDLR/Fyn	-0.002	0.043	-10000	0	-0.1	12	12
MAPK8IP1/MKK7/MAP3K11/JNK1	0.025	0.026	-10000	0	-0.088	4	4
AKT1	-0.018	0.049	-10000	0	-0.14	12	12
MAP2K7	0.01	0	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
DAB1	0.003	0.005	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.002	0.034	-10000	0	-0.089	10	10
LRPAP1/LRP8	0.015	0.003	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.002	0.034	-10000	0	-0.085	10	10
DAB1/alpha3/beta1 Integrin	0.002	0.037	-10000	0	-0.09	10	10
long-term memory	-0.023	0.05	-10000	0	-0.097	23	23
DAB1/LIS1	0.006	0.036	-10000	0	-0.084	10	10
DAB1/CRLK/C3G	0.003	0.034	-10000	0	-0.083	10	10
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
DAB1/NCK2	0.006	0.036	-10000	0	-0.084	10	10
ARHGEF2	0.01	0	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.005	0.005	-10000	0	-10000	0	0
CDK5R1	0.01	0	-10000	0	-10000	0	0
RELN	0.006	0.005	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.001	0.04	-10000	0	-0.1	10	10
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.02	0.053	-10000	0	-0.1	22	22
MAPK8	0.01	0.002	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.004	0.037	-10000	0	-0.089	12	12
ITGB1	0.01	0	-10000	0	-10000	0	0
MAP1B	-0.002	0.054	0.12	9	-0.1	10	19
RELN/LRP8	0.001	0.04	-10000	0	-0.1	10	10
GRIN2B/RELN/LRP8/DAB1/Fyn	0.001	0.04	-10000	0	-0.093	11	11
PI3K	0.012	0.022	-10000	0	-0.12	2	2
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.013	0.016	-10000	0	-0.12	1	1
RAP1A	0.011	0.071	0.14	16	-10000	0	16
PAFAH1B1	0.01	0	-10000	0	-10000	0	0
MAPK8IP1	0.01	0	-10000	0	-10000	0	0
CRLK/C3G	0.015	0	-10000	0	-10000	0	0
GRIN2B	0.007	0.005	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
neuron differentiation	-0.004	0.052	-10000	0	-10000	0	0
neuron adhesion	0.011	0.075	0.14	17	-0.15	1	18
LRP8	0.01	0.002	-10000	0	-10000	0	0
GSK3B	-0.01	0.058	-10000	0	-0.13	12	12
RELN/VLDLR/DAB1/Fyn	0	0.037	-10000	0	-0.085	12	12
MAP3K11	0.01	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.017	0.053	-10000	0	-0.14	12	12
CDK5	0.01	0	-10000	0	-10000	0	0
MAPT	0	0.049	0.36	1	-0.17	2	3
neuron migration	-0.01	0.083	0.19	3	-0.19	10	13
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.053	-10000	0	-10000	0	0
RELN/VLDLR	0.006	0.039	-10000	0	-0.093	10	10

×

EPHB forward 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
Ephrin A5/EPHB2	0.005	0.028	-10000	0	-0.1	5	5
cell-cell adhesion	0.024	0.032	0.087	15	-10000	0	15
Ephrin B/EPHB2/RasGAP	0.015	0.038	-10000	0	-0.088	9	9
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.01	0.018	-10000	0	-0.1	2	2
Ephrin B1/EPHB1	0.001	0.034	-10000	0	-0.1	8	8
HRAS/GDP	-0.011	0.047	-10000	0	-0.14	5	5
Ephrin B/EPHB1/GRB7	0.007	0.043	-10000	0	-0.1	9	9
Endophilin/SYNJ1	-0.001	0.057	0.16	7	-10000	0	7
KRAS	0.01	0.001	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.009	0.047	-10000	0	-0.1	11	11
endothelial cell migration	0.018	0.021	-10000	0	-0.086	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.007	0.005	-10000	0	-10000	0	0
PAK1	-0.003	0.058	0.16	7	-10000	0	7
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.001	0.058	0.16	7	-10000	0	7
DNM1	0.009	0.003	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.002	0.063	0.14	10	-0.16	2	12
lamellipodium assembly	-0.024	0.032	-10000	0	-0.087	15	15
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.01	0.056	-10000	0	-0.15	10	10
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPHB2	0.009	0.003	-10000	0	-10000	0	0
EPHB3	0.009	0.003	-10000	0	-10000	0	0
EPHB1	0.008	0.004	-10000	0	-10000	0	0
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.011	0.06	0.11	8	-0.15	5	13
Ephrin B/EPHB2	0.011	0.033	-10000	0	-0.086	8	8
Ephrin B/EPHB3	0.012	0.031	-10000	0	-0.086	7	7
JNK cascade	0.003	0.067	0.14	13	-10000	0	13
Ephrin B/EPHB1	0.004	0.044	-10000	0	-0.1	11	11
RAP1/GDP	0.003	0.062	0.15	1	-0.14	5	6
EFNB2	0.01	0.002	-10000	0	-10000	0	0
EFNB3	0.009	0.003	-10000	0	-10000	0	0
EFNB1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0	0.041	-10000	0	-0.098	11	11
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.006	0.053	-10000	0	-0.14	8	8
Rap1/GTP	-0.025	0.033	-10000	0	-0.089	15	15
axon guidance	0.005	0.028	-10000	0	-0.1	5	5
MAPK3	-0.01	0.064	-10000	0	-0.26	2	2
MAPK1	-0.01	0.064	-10000	0	-0.26	2	2
Rac1/GDP	0.003	0.07	0.21	2	-0.15	5	7
actin cytoskeleton reorganization	-0.027	0.034	-10000	0	-0.11	9	9
CDC42/GDP	0.003	0.07	0.21	2	-0.15	5	7
PI3K	0.02	0.021	-10000	0	-0.086	3	3
EFNA5	0.01	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.012	0.013	-10000	0	-0.1	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.006	0.045	-10000	0	-0.14	8	8
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.026	0.034	-10000	0	-0.092	15	15
PTK2	0	0.01	-10000	0	-10000	0	0
MAP4K4	0.003	0.067	0.14	13	-0.088	12	25
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.01	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.015	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.006	0.072	0.24	2	-0.17	2	4
MAP2K1	-0.016	0.06	-10000	0	-0.17	8	8
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.004	0.042	-10000	0	-0.093	12	12
cell migration	-0.011	0.08	0.18	1	-0.2	9	10
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.001	0.058	0.16	7	-10000	0	7
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.013	0.031	-10000	0	-0.15	2	2
HRAS/GTP	-0.003	0.043	-10000	0	-0.089	15	15
Ephrin B1/EPHB1-2	0.001	0.038	-10000	0	-0.091	11	11
cell adhesion mediated by integrin	0.007	0.026	0.086	3	-0.14	1	4
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.045	-10000	0	-0.092	15	15
RAC1-CDC42/GTP	-0.026	0.034	-10000	0	-0.088	17	17
RASA1	0.01	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.003	0.062	0.15	1	-0.14	5	6
ruffle organization	-0.001	0.076	0.14	14	-0.15	2	16
NCK1	0.01	0.001	-10000	0	-10000	0	0
receptor internalization	-0.005	0.049	0.14	6	-10000	0	6
Ephrin B/EPHB2/KALRN	0.016	0.036	-10000	0	-0.088	8	8
ROCK1	0.001	0.037	0.14	5	-0.091	2	7
RAS family/GDP	-0.027	0.036	-10000	0	-0.12	6	6
Rac1/GTP	-0.025	0.033	-10000	0	-0.09	15	15
Ephrin B/EPHB1/Src/Paxillin	-0.016	0.065	-10000	0	-0.17	11	11

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.036	0.11	-9999	-0.33	10	10
KLHL20	-0.01	0.044	-9999	-0.15	2	2
CYFIP2	0.009	0.004	-9999	-10000	0	0
Rac1/GDP	-0.02	0.064	-9999	-0.19	10	10
ENAH	-0.036	0.11	-9999	-0.33	10	10
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
CDC42/GTP	-0.005	0.04	-9999	-0.11	10	10
ABI1/Sra1/Nap1	-0.018	0.032	-9999	-0.1	9	9
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.007	0.044	-9999	-0.093	13	13
RAPGEF1	-0.036	0.098	-9999	-0.3	10	10
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.033	0.12	-9999	-0.34	10	10
CRK	-0.036	0.1	-9999	-0.31	10	10
E-cadherin/gamma catenin/alpha catenin	0.008	0.037	-9999	-0.1	8	8
alphaE/beta7 Integrin	0.01	0.026	-9999	-0.12	3	3
IQGAP1	0.01	0.002	-9999	-10000	0	0
NCKAP1	0.01	0.001	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.017	0.017	-9999	-0.091	2	2
DLG1	-0.037	0.11	-9999	-0.34	10	10
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.022	0.028	-9999	-0.089	10	10
MLLT4	0.01	0.002	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.017	0.013	-9999	-0.091	1	1
PI3K	-0.027	0.035	-9999	-0.11	10	10
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.001	0.042	-9999	-0.12	8	8
TIAM1	0.009	0.003	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0.011	0.037	-9999	-0.086	10	10
AKT1	-0.018	0.022	-9999	-0.07	10	10
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.009	0.003	-9999	-10000	0	0
RhoA/GDP	-0.02	0.064	-9999	-0.19	10	10
actin cytoskeleton organization	-0.007	0.034	-9999	-0.12	1	1
CDC42/GDP	-0.02	0.064	-9999	-0.19	10	10
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.008	0.045	-9999	-0.14	8	8
ITGB7	0.01	0.002	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.012	0.039	-9999	-0.093	10	10
E-cadherin/Ca2+/beta catenin/alpha catenin	0.005	0.034	-9999	-0.085	10	10
mol:GDP	-0.028	0.07	-9999	-0.21	10	10
CDC42/GTP/IQGAP1	0.008	0.025	-9999	-0.1	4	4
JUP	0.01	0.001	-9999	-10000	0	0
p120 catenin/RhoA/GDP	-0.016	0.067	-9999	-0.19	10	10
RAC1/GTP/IQGAP1	0.008	0.025	-9999	-0.1	4	4
PIP5K1C/AP1M1	0.015	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.004	0.022	-9999	-0.071	1	1
NME1	0.01	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.036	0.11	-9999	-0.33	10	10
regulation of cell-cell adhesion	-0.019	0.03	-9999	-0.097	10	10
WASF2	-0.01	0.019	-9999	-0.057	9	9
Rap1/GTP	-0.007	0.043	-9999	-0.12	10	10
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.014	0.041	-9999	-0.088	11	11
CCND1	-0.005	0.027	-9999	-0.085	1	1
VAV2	-0.031	0.11	-9999	-0.31	10	10
RAP1/GDP	-0.011	0.051	-9999	-0.14	10	10
adherens junction assembly	-0.035	0.11	-9999	-0.32	10	10
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.005	0.038	-9999	-0.085	12	12
E-cadherin/beta catenin	-0.018	0.069	-9999	-0.21	9	9
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.036	0.11	-9999	-0.33	10	10
PIK3CA	0.01	0.002	-9999	-10000	0	0
Rac1/GTP	-0.016	0.059	-9999	-0.18	9	9
E-cadherin/beta catenin/alpha catenin	0.005	0.041	-9999	-0.1	10	10
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.034	0.12	-9999	-0.34	10	10

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.003	0.089	0.17	3	-0.34	4	7
Syndecan-4/Syndesmos	-0.017	0.14	0.21	3	-0.33	11	14
positive regulation of JNK cascade	-0.016	0.13	0.19	3	-0.35	9	12
Syndecan-4/ADAM12	-0.02	0.14	0.21	3	-0.34	11	14
CCL5	0.007	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
DNM2	0.01	0	-10000	0	-10000	0	0
ITGA5	0.01	0.002	-10000	0	-10000	0	0
SDCBP	0.01	0	-10000	0	-10000	0	0
PLG	-0.001	0.007	-10000	0	-0.022	5	5
ADAM12	0.009	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.008	0.006	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.029	0.14	0.21	2	-0.34	11	13
Syndecan-4/CXCL12/CXCR4	-0.017	0.14	0.2	3	-0.36	9	12
Syndecan-4/Laminin alpha3	-0.018	0.14	0.21	3	-0.33	11	14
MDK	0.009	0.003	-10000	0	-10000	0	0
Syndecan-4/FZD7	-0.021	0.14	0.21	2	-0.34	11	13
Syndecan-4/Midkine	-0.021	0.14	0.21	3	-0.35	11	14
FZD7	0.01	0.002	-10000	0	-10000	0	0
Syndecan-4/FGFR1/FGF	-0.03	0.13	-10000	0	-0.33	10	10
THBS1	0.008	0.004	-10000	0	-10000	0	0
integrin-mediated signaling pathway	-0.025	0.13	0.2	2	-0.34	10	12
positive regulation of MAPKKK cascade	-0.016	0.13	0.19	3	-0.35	9	12
Syndecan-4/TACI	-0.025	0.13	0.2	3	-0.33	11	14
CXCR4	0.009	0.003	-10000	0	-10000	0	0
cell adhesion	-0.012	0.047	-10000	0	-0.16	6	6
Syndecan-4/Dynamin	-0.017	0.14	0.21	3	-0.33	11	14
Syndecan-4/TSP1	-0.029	0.14	0.21	1	-0.35	10	11
Syndecan-4/GIPC	-0.017	0.14	0.21	3	-0.33	11	14
Syndecan-4/RANTES	-0.031	0.14	0.21	2	-0.35	11	13
ITGB1	0.01	0	-10000	0	-10000	0	0
LAMA1	0.008	0.004	-10000	0	-10000	0	0
LAMA3	0.01	0.002	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.004	0.003	-10000	0	-10000	0	0
Syndecan-4/alpha-Actinin	-0.017	0.14	0.21	3	-0.33	11	14
TFPI	0.009	0.003	-10000	0	-10000	0	0
F2	0	0.01	-10000	0	-0.022	9	9
alpha5/beta1 Integrin	0.007	0.034	-10000	0	-0.12	5	5
positive regulation of cell adhesion	-0.032	0.13	0.2	2	-0.33	12	14
ACTN1	0.01	0	-10000	0	-10000	0	0
TNC	0.008	0.004	-10000	0	-10000	0	0
Syndecan-4/CXCL12	-0.018	0.14	0.21	3	-0.34	10	13
FGF6	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
CXCL12	0.009	0.003	-10000	0	-10000	0	0
TNFRSF13B	0.003	0.005	-10000	0	-10000	0	0
FGF2	0.009	0.004	-10000	0	-10000	0	0
FGFR1	0.01	0.002	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.028	0.13	0.2	1	-0.33	11	12
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.007	0.008	-10000	0	-10000	0	0
cell migration	-0.005	0.003	-10000	0	-10000	0	0
PRKCD	0.006	0.012	-10000	0	-0.027	5	5
vasculogenesis	-0.028	0.13	0.2	1	-0.34	10	11
SDC4	-0.023	0.14	0.22	3	-0.34	11	14
Syndecan-4/Tenascin C	-0.026	0.14	0.21	2	-0.35	10	12
Syndecan-4/PI-4-5-P2/PKC alpha	-0.007	0.005	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.017	0.14	0.21	3	-0.33	11	14
MMP9	0.007	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.012	0.048	-10000	0	-0.16	6	6
cytoskeleton organization	-0.016	0.13	0.2	3	-0.32	11	14
GIPC1	0.01	0	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.015	0.13	0.21	3	-0.33	9	12

×

Visual signal transduction: Rods

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
mol:K +	0.01	0.001	-10000	0	-10000	0	0
GNAT1/GTP	-0.01	0.037	-10000	0	-0.12	8	8
Metarhodopsin II/Arrestin	-0.008	0.035	-10000	0	-0.099	10	10
PDE6G/GNAT1/GTP	-0.003	0.033	-10000	0	-0.1	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.003	0.005	-10000	0	-10000	0	0
GRK1	0.003	0.005	-10000	0	-10000	0	0
CNG Channel	-0.005	0.043	-10000	0	-0.11	11	11
mol:Na +	-0.021	0.048	-10000	0	-0.089	24	24
mol:ADP	0.003	0.005	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.013	0.027	-10000	0	-0.1	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.021	0.05	-10000	0	-0.09	24	24
CNGB1	0.003	0.004	-10000	0	-10000	0	0
RDH5	0.01	0.002	-10000	0	-10000	0	0
SAG	0.003	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.029	0.17	0.34	14	-0.17	3	17
Na + (4 Units)	-0.021	0.047	-10000	0	-0.086	24	24
RGS9	0.009	0.003	-10000	0	-10000	0	0
GNB1/GNGT1	0.01	0.005	-10000	0	-10000	0	0
GNAT1/GDP	0	0.037	-10000	0	-0.086	12	12
GUCY2D	0.008	0.005	-10000	0	-10000	0	0
GNGT1	0.004	0.005	-10000	0	-10000	0	0
GUCY2F	0.001	0.002	-10000	0	-10000	0	0
GNB5	0.01	0.002	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.006	0.034	-10000	0	-0.094	10	10
mol:11-cis-retinal	0.01	0.002	-10000	0	-10000	0	0
mol:cGMP	-0.02	0.05	-10000	0	-0.095	22	22
GNB1	0.01	0	-10000	0	-10000	0	0
Rhodopsin	-0.006	0.042	-10000	0	-0.12	9	9
SLC24A1	0.01	0.001	-10000	0	-10000	0	0
CNGA1	0.006	0.005	-10000	0	-10000	0	0
Metarhodopsin II	-0.006	0.029	-10000	0	-0.088	9	9
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	-0.018	0.055	-10000	0	-0.1	21	21
RGS9BP	0.009	0.003	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	-0.028	0.064	-10000	0	-0.15	16	16
GCAP Family/Ca ++	-0.011	0.042	-10000	0	-0.094	15	15
PDE6A/B	0.008	0.026	-10000	0	-0.12	3	3
mol:Pi	0.013	0.027	-10000	0	-0.1	4	4
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.001	0.03	-10000	0	-0.09	8	8
PDE6B	0.01	0.002	-10000	0	-10000	0	0
PDE6A	0.008	0.004	-10000	0	-10000	0	0
PDE6G	0.01	0.002	-10000	0	-10000	0	0
RHO	0.004	0.005	-10000	0	-10000	0	0
PDE6	0.015	0.033	-10000	0	-0.085	7	7
GUCA1A	0.005	0.005	-10000	0	-10000	0	0
GC2/GCAP Family	-0.012	0.042	-10000	0	-0.094	16	16
GUCA1C	0.001	0.004	-10000	0	-10000	0	0
GUCA1B	0.008	0.004	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.028	0.11	-10000	0	-0.26	12	12
STMN1	-0.003	0.005	0.02	1	-10000	0	1
Aurora B/RasGAP/Survivin	0.004	0.056	-10000	0	-0.16	8	8
Chromosomal passenger complex/Cul3 protein complex	-0.026	0.084	-10000	0	-0.18	14	14
BIRC5	0.008	0.006	-10000	0	-0.01	7	7
DES	-0.084	0.24	-10000	0	-0.68	11	11
Aurora C/Aurora B/INCENP	0.005	0.039	-10000	0	-0.096	10	10
Aurora B/TACC1	0.006	0.031	-10000	0	-0.1	6	6
Aurora B/PP2A	0.005	0.038	-10000	0	-0.13	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.003	0.002	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	0.002	0.005	0.012	11	-10000	0	11
NDC80	-0.003	0.005	0.008	8	-10000	0	8
Cul3 protein complex	0.011	0.033	-10000	0	-0.1	6	6
KIF2C	-0.032	0.14	-10000	0	-0.32	9	9
PEBP1	0.008	0.008	-10000	0	-0.013	9	9
KIF20A	0.01	0.004	0.023	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.003	0.04	-10000	0	-0.13	7	7
SEPT1	0.01	0.001	-10000	0	-10000	0	0
SMC2	0.01	0	-10000	0	-10000	0	0
SMC4	0.01	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.044	0.16	-10000	0	-0.6	6	6
PSMA3	0.01	0	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.003	0.012	5	-10000	0	5
H3F3B	0.005	0.003	0.011	6	-0.003	1	7
AURKB	0.01	0.007	0.033	2	-0.014	1	3
AURKC	0.009	0.003	-10000	0	-10000	0	0
CDCA8	0.008	0.008	-10000	0	-0.013	9	9
cytokinesis	-0.046	0.14	-10000	0	-0.33	12	12
Aurora B/Septin1	-0.037	0.14	-10000	0	-0.32	12	12
AURKA	0.01	0.006	0.026	3	-0.008	5	8
INCENP	0.007	0.009	-10000	0	-0.015	12	12
KLHL13	0.009	0.003	-10000	0	-10000	0	0
BUB1	0.009	0.004	-10000	0	-0.007	1	1
hSgo1/Aurora B/Survivin	0	0.059	-10000	0	-0.15	9	9
EVI5	0.008	0.006	-10000	0	-0.01	8	8
RhoA/GTP	-0.026	0.13	-10000	0	-0.3	12	12
SGOL1	0.009	0.004	-10000	0	-10000	0	0
CENPA	-0.039	0.15	-10000	0	-0.44	8	8
NCAPG	0.008	0.004	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.005	0.038	-10000	0	-0.13	6	6
NCAPD2	0.01	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.005	0.038	-10000	0	-0.13	6	6
RHOA	0.01	0	-10000	0	-10000	0	0
NCAPH	0.009	0.003	-10000	0	-10000	0	0
NPM1	-0.025	0.1	-10000	0	-0.38	6	6
RASA1	0.01	0.001	-10000	0	-10000	0	0
KLHL9	0.01	0	-10000	0	-10000	0	0
mitotic prometaphase	-0.001	0.003	-10000	0	-0.011	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.038	-10000	0	-0.13	6	6
PPP1CC	0.01	0	-10000	0	-10000	0	0
Centraspindlin	-0.032	0.14	-10000	0	-0.32	12	12
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
NSUN2	-0.025	0.1	-10000	0	-0.38	6	6
MYLK	0.004	0.003	0.011	6	-0.003	1	7
KIF23	0.008	0.007	-10000	0	-0.013	7	7
VIM	-0.003	0.005	0.02	1	-10000	0	1
RACGAP1	0.008	0.008	-10000	0	-0.013	10	10
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.025	0.1	-10000	0	-0.38	6	6
Chromosomal passenger complex	-0.045	0.15	0.085	1	-0.3	14	15
Chromosomal passenger complex/EVI5	0.012	0.069	0.099	5	-0.16	9	14
TACC1	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.01	0	-10000	0	-10000	0	0
CUL3	0.01	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.01	0.002	-10000	0	-10000	0	0
ANTXR2	0.01	0.002	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.008	-10000	0	-0.028	7	7
monocyte activation	-0.016	0.094	-10000	0	-0.34	6	6
MAP2K2	0.005	0.004	-10000	0	-10000	0	0
MAP2K1	-0.005	0.007	-10000	0	-0.028	7	7
MAP2K7	-0.005	0.007	-10000	0	-0.028	7	7
MAP2K6	-0.005	0.007	-10000	0	-0.028	7	7
CYAA	-0.01	0.022	-10000	0	-0.082	7	7
MAP2K4	-0.005	0.007	-10000	0	-0.028	7	7
IL1B	0.001	0.045	0.16	5	-0.073	6	11
Channel	0.004	0.029	-10000	0	-0.089	7	7
NLRP1	-0.004	0.007	-10000	0	-0.028	6	6
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.002	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.008	0.028	7	-10000	0	7
MAPK3	-0.005	0.007	-10000	0	-0.028	7	7
MAPK1	-0.005	0.007	-10000	0	-0.028	7	7
PGR	-0.004	0.006	-10000	0	-0.026	6	6
PA/Cellular Receptors	0.004	0.032	-10000	0	-0.1	7	7
apoptosis	-0.003	0.008	-10000	0	-0.028	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.03	-10000	0	-0.092	7	7
macrophage activation	-0.006	0.007	-10000	0	-10000	0	0
TNF	0.007	0.005	-10000	0	-10000	0	0
VCAM1	-0.022	0.092	-10000	0	-0.34	6	6
platelet activation	0.002	0.008	-10000	0	-10000	0	0
MAPKKK cascade	0.006	0.009	-10000	0	-10000	0	0
IL18	-0.005	0.034	0.12	3	-0.078	7	10
negative regulation of macrophage activation	-0.003	0.008	-10000	0	-0.028	7	7
LEF	-0.003	0.008	-10000	0	-0.028	7	7
CASP1	-0.002	0.006	-10000	0	-0.026	5	5
mol:cAMP	0.002	0.009	-10000	0	-10000	0	0
necrosis	-0.003	0.008	-10000	0	-0.028	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.005	0.027	-10000	0	-0.083	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.029	0.072	-10000	0	-0.12	26	26
SMAD6-7/SMURF1	0.018	0.019	-10000	0	-0.1	2	2
NOG	0.006	0.005	-10000	0	-10000	0	0
SMAD9	-0.005	0.037	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
SMAD5	-0.027	0.09	0.15	1	-0.25	5	6
BMP7/USAG1	-0.02	0.057	-10000	0	-0.13	16	16
SMAD5/SKI	-0.022	0.089	0.15	1	-0.24	5	6
SMAD1	0.002	0.015	-10000	0	-10000	0	0
BMP2	0.01	0.002	-10000	0	-10000	0	0
SMAD1/SMAD1/SMAD4	0.006	0.023	-10000	0	-10000	0	0
BMPR1A	0.01	0.001	-10000	0	-10000	0	0
BMPR1B	0.007	0.005	-10000	0	-10000	0	0
BMPR1A-1B/BAMBI	-0.013	0.054	-10000	0	-0.1	21	21
AHSG	0.003	0.005	-10000	0	-10000	0	0
CER1	0	0.001	-10000	0	-10000	0	0
BMP2-4/CER1	0.006	0.028	-10000	0	-0.1	5	5
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.025	0.083	-10000	0	-0.26	4	4
BMP2-4 (homodimer)	0.006	0.034	-10000	0	-0.12	5	5
RGMB	0.01	0.002	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.007	0.052	-10000	0	-0.093	21	21
RGMA	0.01	0	-10000	0	-10000	0	0
SMURF1	0.01	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.039	0.08	-10000	0	-0.16	21	21
BMP2-4/USAG1	-0.011	0.048	-10000	0	-0.1	17	17
SMAD6/SMURF1/SMAD5	-0.022	0.089	0.15	1	-0.24	5	6
SOSTDC1	0.005	0.005	-10000	0	-10000	0	0
BMP7/BMPR2/BMPR1A-1B	-0.018	0.059	-10000	0	-0.11	22	22
SKI	0.01	0	-10000	0	-10000	0	0
BMP6 (homodimer)	0.01	0	-10000	0	-10000	0	0
HFE2	0.002	0.004	-10000	0	-10000	0	0
ZFYVE16	0.01	0.001	-10000	0	-10000	0	0
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
BMP2-4/CHRD	0	0.053	-10000	0	-0.13	11	11
SMAD5/SMAD5/SMAD4	-0.022	0.089	0.15	1	-0.24	5	6
MAPK1	0.01	0	-10000	0	-10000	0	0
TAK1/TAB family	-0.032	0.08	-10000	0	-0.25	6	6
BMP7 (homodimer)	0.007	0.005	-10000	0	-10000	0	0
NUP214	0.01	0	-10000	0	-10000	0	0
BMP6/FETUA	0.01	0.004	-10000	0	-10000	0	0
SMAD1/SKI	0.007	0.018	-10000	0	-10000	0	0
SMAD6	0.01	0.002	-10000	0	-10000	0	0
CTDSP2	0.01	0	-10000	0	-10000	0	0
BMP2-4/FETUA	0.008	0.029	-10000	0	-0.1	5	5
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.006	0.005	-10000	0	-10000	0	0
BMPR2 (homodimer)	0.01	0	-10000	0	-10000	0	0
GADD34/PP1CA	0.019	0.014	-10000	0	-0.1	1	1
BMPR1A-1B (homodimer)	-0.023	0.061	-10000	0	-0.12	21	21
CHRDL1	0.008	0.005	-10000	0	-10000	0	0
ENDOFIN/SMAD1	0.006	0.018	-10000	0	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.011	0.027	-10000	0	-10000	0	0
SMAD6/SMURF1	0.01	0	-10000	0	-10000	0	0
BAMBI	0.01	0	-10000	0	-10000	0	0
SMURF2	0.01	0.002	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.005	0.052	-10000	0	-0.12	13	13
BMP2-4/GREM1	-0.003	0.044	-10000	0	-0.1	13	13
SMAD7	0.01	0	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.008	0.047	-10000	0	-10000	0	0
SMAD1/SMAD6	0.007	0.018	-10000	0	-10000	0	0
TAK1/SMAD6	0.008	0.03	-10000	0	-0.12	4	4
BMP7	0.007	0.005	-10000	0	-10000	0	0
BMP6	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.024	0.08	-10000	0	-0.25	4	4
PPM1A	0.01	0	-10000	0	-10000	0	0
SMAD1/SMURF2	0.007	0.017	-10000	0	-10000	0	0
SMAD7/SMURF1	0.015	0	-10000	0	-10000	0	0
CTDSPL	0.01	0	-10000	0	-10000	0	0
PPP1CA	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0.001	-10000	0	-10000	0	0
CTDSP1	0.01	0	-10000	0	-10000	0	0
PPP1R15A	0.01	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.06	0.11	-10000	0	-0.21	24	24
CHRD	0.009	0.003	-10000	0	-10000	0	0
BMPR2	0.01	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.037	0.079	-10000	0	-0.16	22	22
BMP4	0.01	0.002	-10000	0	-10000	0	0
FST	0.006	0.005	-10000	0	-10000	0	0
BMP2-4/NOG	0.008	0.032	-10000	0	-0.1	6	6
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.014	0.058	-10000	0	-0.1	22	22

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.011	0.022	-9999	-0.12	2	2
PTK2	-0.017	0.086	-9999	-0.27	8	8
positive regulation of JNK cascade	-0.013	0.081	-9999	-0.26	8	8
CDC42/GDP	-0.013	0.11	-9999	-0.34	8	8
Rac1/GDP	-0.013	0.11	-9999	-0.33	8	8
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
CDC42/GTP	-0.013	0.099	-9999	-0.31	8	8
nectin-3/I-afadin	0.001	0.042	-9999	-0.12	8	8
RAPGEF1	-0.025	0.11	-9999	-0.36	8	8
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.027	0.13	-9999	-0.4	8	8
PDGFB-D/PDGFRB	0.01	0	-9999	-10000	0	0
TLN1	-0.011	0.025	-9999	-0.086	8	8
Rap1/GTP	-0.017	0.085	-9999	-0.27	8	8
IQGAP1	0.01	0.002	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.017	0.017	-9999	-0.091	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.001	0.042	-9999	-0.12	8	8
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	-0.023	0.13	-9999	-0.4	8	8
MLLT4	0.01	0.002	-9999	-10000	0	0
PIK3CA	0.01	0.002	-9999	-10000	0	0
PI3K	0.016	0.041	-9999	-0.096	9	9
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.012	0.022	-9999	-0.12	2	2
positive regulation of lamellipodium assembly	-0.013	0.085	-9999	-0.27	8	8
PVRL1	0.01	0	-9999	-10000	0	0
PVRL3	0.009	0.003	-9999	-10000	0	0
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.009	0.003	-9999	-10000	0	0
CLDN1	0.008	0.004	-9999	-10000	0	0
JAM-A/CLDN1	0.006	0.042	-9999	-0.093	12	12
SRC	-0.03	0.14	-9999	-0.44	8	8
ITGB3	0.01	0.002	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	0.012	0.022	-9999	-0.12	2	2
FARP2	-0.02	0.12	-9999	-0.39	8	8
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.009	0.037	-9999	-0.1	8	8
nectin-1/I-afadin	0.012	0.022	-9999	-0.12	2	2
nectin-2/I-afadin	0.012	0.022	-9999	-0.12	2	2
RAC1/GTP/IQGAP1/filamentous actin	0.008	0.025	-9999	-0.1	4	4
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.009	0.037	-9999	-0.1	8	8
CDC42/GTP/IQGAP1/filamentous actin	0.008	0.025	-9999	-0.1	4	4
F11R	0.01	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.013	0.081	-9999	-0.26	8	8
alphaV/beta3 Integrin/Talin	0	0.033	-9999	-0.15	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.012	0.022	-9999	-0.12	2	2
nectin-2(dimer)/I-afadin/I-afadin	0.012	0.022	-9999	-0.12	2	2
PIP5K1C	-0.01	0.027	-9999	-0.091	8	8
VAV2	-0.021	0.13	-9999	-0.4	8	8
RAP1/GDP	-0.011	0.1	-9999	-0.32	8	8
ITGAV	0.01	0.001	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.009	0.037	-9999	-0.1	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.001	0.042	-9999	-0.12	8	8
Rac1/GTP	-0.013	0.1	-9999	-0.32	8	8
PTPRM	-0.006	0.031	-9999	-0.1	8	8
E-cadherin/beta catenin/alpha catenin	0.013	0.043	-9999	-0.092	11	11
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.01	0	-10000	0	-10000	0	0
HDAC4	0.01	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.004	0.037	-10000	0	-0.12	7	7
CDKN1A	-0.04	0.12	-10000	0	-0.43	7	7
KAT2B	0.01	0.002	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
FOXO3	-0.001	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
FOXO4	0.005	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
TAT	0.002	0.004	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.003	0.002	0	8	-10000	0	8
PPARGC1A	0.007	0.005	-10000	0	-10000	0	0
FHL2	0.009	0.003	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.024	0.03	0.12	7	-10000	0	7
HIST2H4A	0.004	0.037	0.12	7	-10000	0	7
SIRT1/FOXO3a	0.016	0.031	0.12	7	-10000	0	7
SIRT1	0.023	0.042	0.16	7	-10000	0	7
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.029	0.027	0.12	7	-10000	0	7
SIRT1/Histone H1b	0.022	0.032	0.12	7	-10000	0	7
apoptosis	-0.028	0.027	-10000	0	-0.12	7	7
SIRT1/PGC1A	0	0.043	0.11	3	-0.1	10	13
p53/SIRT1	0.039	0.08	0.3	7	-10000	0	7
SIRT1/FOXO4	0.02	0.031	0.12	7	-10000	0	7
FOXO1/FHL2/SIRT1	0.019	0.041	0.11	7	-0.092	6	13
HIST1H1E	0.004	0.001	-10000	0	0	2	2
SIRT1/p300	0.024	0.03	0.12	7	-10000	0	7
muscle cell differentiation	-0.018	0.035	0.1	2	-0.11	7	9
TP53	0.023	0.042	0.16	7	-10000	0	7
KU70/SIRT1/BAX	0.029	0.027	0.12	7	-10000	0	7
CREBBP	0.01	0	-10000	0	-10000	0	0
MEF2D	0.01	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.018	0.031	0.12	7	-10000	0	7
ACSS2	0.004	0.037	0.12	7	-10000	0	7
SIRT1/PCAF/MYOD	0.018	0.035	0.12	7	-0.1	2	9

×

TRAIL signaling pathway

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
TNFSF10	0.009	0.003	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	-0.022	0.067	-10000	0	-0.14	18	18
MAP2K4	-0.007	0.052	-10000	0	-0.16	5	5
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.007	0.005	-10000	0	-10000	0	0
SMPD1	-0.002	0.025	-10000	0	-0.1	5	5
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.008	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.006	0.034	-10000	0	-0.12	5	5
TRAIL/TRAILR3	-0.009	0.054	-10000	0	-0.14	10	10
TRAIL/TRAILR1	-0.011	0.055	-10000	0	-0.13	13	13
TRAIL/TRAILR4	-0.022	0.067	-10000	0	-0.14	18	18
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.043	-10000	0	-0.097	13	13
IKK complex	0	0.019	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.008	0	-10000	0	-10000	0	0
MAPK3	-0.005	0.002	-10000	0	-10000	0	0
MAP3K1	-0.007	0.052	-10000	0	-0.17	5	5
TRAILR4 (trimer)	0.008	0.005	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.007	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.018	0.061	-10000	0	-0.15	13	13
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	-0.005	0.002	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.006	0.046	-10000	0	-0.094	13	13
mol:ceramide	-0.002	0.025	-10000	0	-0.1	5	5
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.005	0.061	0.13	3	-0.19	5	8
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.007	0.005	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.003	0.048	-10000	0	-0.11	13	13
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.01	0.038	0.13	2	-0.14	2	4
JNK cascade	-0.022	0.067	-10000	0	-0.14	18	18
TRAIL (trimer)	0.009	0.003	-10000	0	-10000	0	0
TNFRSF10C	0.007	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.002	0.043	-10000	0	-0.092	13	13
TRAIL/TRAILR2/FADD	0.012	0.03	-10000	0	-0.1	5	5
cell death	-0.002	0.025	-10000	0	-0.1	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0.037	-10000	0	-0.14	5	5
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	0.003	0.004	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.021	0.029	-10000	0	-0.088	5	5

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.013	0.15	0.46	1	-0.9	2	3
VDR	0.009	0.003	-10000	0	-10000	0	0
FAM120B	0.01	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.002	0.092	0.31	3	-0.28	3	6
RXRs/LXRs/DNA/Oxysterols	0.005	0.12	0.39	3	-0.41	3	6
MED1	0.01	0	-10000	0	-10000	0	0
mol:9cRA	0.004	0.02	0.072	5	-0.046	2	7
RARs/THRs/DNA/Src-1	-0.008	0.053	-10000	0	-0.16	8	8
RXRs/NUR77	0.019	0.058	0.2	3	-0.1	8	11
RXRs/PPAR	-0.027	0.075	0.12	3	-0.15	18	21
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.006	0.014	-10000	0	-0.12	1	1
RARs/VDR/DNA/Vit D3	0.013	0.031	-10000	0	-0.086	7	7
RARA	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.009	0.003	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.013	0.03	0.064	3	-0.085	6	9
RARG	0.01	0	-10000	0	-10000	0	0
RPS6KB1	-0.005	0.07	0.29	1	-0.39	2	3
RARs/THRs/DNA/SMRT	-0.008	0.053	-10000	0	-0.16	8	8
THRA	0.01	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.006	0.014	-10000	0	-0.12	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	0.022	0.077	0.27	5	-0.19	1	6
NR1H4	0.003	0.005	-10000	0	-10000	0	0
RXRs/LXRs/DNA	0.027	0.079	0.31	3	-0.19	3	6
NR1H2	0.014	0.021	0.085	5	-0.044	3	8
NR1H3	0.014	0.021	0.083	5	-0.047	3	8
RXRs/VDR/DNA/Vit D3	0.014	0.046	0.19	1	-0.11	3	4
NR4A1	0.01	0.001	-10000	0	-10000	0	0
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0	0.057	0.15	3	-0.14	7	10
RXRG	0.011	0.018	0.084	3	-0.046	2	5
RXR alpha/CCPG	0.018	0.016	0.07	5	-10000	0	5
RXRA	0.014	0.021	0.085	5	-0.044	3	8
RXRB	0.014	0.021	0.083	5	-0.047	3	8
THRB	0.009	0.004	-10000	0	-10000	0	0
PPARG	0.006	0.005	-10000	0	-10000	0	0
PPARD	0.01	0	-10000	0	-10000	0	0
TNF	0.002	0.15	0.46	3	-0.53	3	6
mol:Oxysterols	0.004	0.02	0.074	5	-0.039	3	8
cholesterol transport	0.005	0.12	0.39	3	-0.4	3	6
PPARA	0.01	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.009	0.003	-10000	0	-10000	0	0
RXRs/NUR77/BCL2	-0.006	0.049	-10000	0	-0.15	8	8
SREBF1	0.004	0.11	0.36	3	-0.38	3	6
RXRs/RXRs/DNA/9cRA	0.021	0.077	0.27	5	-0.19	1	6
ABCA1	-0.005	0.16	0.41	3	-0.67	3	6
RARs/THRs	0.015	0.039	-10000	0	-0.097	8	8
RXRs/FXR	0.017	0.056	0.2	3	-0.11	4	7
BCL2	0.01	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.025	0.12	-10000	0	-0.39	2	2
UGCG	-0.039	0.15	-10000	0	-0.62	5	5
AKT1/mTOR/p70S6K/Hsp90/TERT	0.018	0.13	0.35	5	-0.24	1	6
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.039	0.15	-10000	0	-0.61	5	5
mol:DAG	-0.019	0.13	-10000	0	-0.84	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.097	-10000	0	-0.27	6	6
FRAP1	0.007	0.16	0.37	5	-0.35	3	8
FOXO3	0.002	0.15	0.33	5	-0.31	6	11
AKT1	0.002	0.16	0.31	9	-0.32	6	15
GAB2	0.011	0.002	-10000	0	-10000	0	0
SMPD1	-0.001	0.019	-10000	0	-10000	0	0
SGMS1	-0.017	0.1	-10000	0	-0.64	2	2
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	-0.005	0.015	-10000	0	-0.097	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.015	0.13	0.23	3	-0.35	7	10
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.014	0.022	-10000	0	-0.12	2	2
RPS6KB1	0.023	0.091	0.26	8	-10000	0	8
mol:sphingomyelin	-0.019	0.13	-10000	0	-0.84	2	2
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	0.01	0.003	-10000	0	-10000	0	0
PIK3R1	0.011	0.002	-10000	0	-10000	0	0
JAK1	0.011	0.002	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.007	0.14	0.39	1	-10000	0	1
MYB	0.002	0.27	0.48	8	-0.88	5	13
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.045	0.1	-10000	0	-0.29	9	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.028	0.081	0.22	8	-10000	0	8
mol:PI-3-4-5-P3	-0.041	0.1	-10000	0	-0.3	8	8
Rac1/GDP	0.006	0.016	-10000	0	-0.087	2	2
T cell proliferation	0.001	0.15	0.3	9	-0.29	8	17
SHC1	0.011	0.002	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.015	0.054	0.17	8	-0.063	4	12
PRKCZ	-0.026	0.13	0.33	4	-0.28	10	14
NF kappa B1 p50/RelA	0.006	0.14	0.28	8	-0.28	6	14
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.043	0.11	-10000	0	-0.3	8	8
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	0.008	0.005	-10000	0	-10000	0	0
IL2RB	0.009	0.004	-10000	0	-10000	0	0
TERT	0.007	0.005	-10000	0	-10000	0	0
E2F1	0.025	0.16	0.41	8	-0.41	5	13
SOS1	0.011	0.002	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.008	0.029	0.03	4	-0.093	8	12
PTPN11	0.011	0.002	-10000	0	-10000	0	0
IL2RG	0.007	0.005	-10000	0	-10000	0	0
actin cytoskeleton organization	0.001	0.15	0.3	9	-0.29	8	17
GRB2	0.011	0.002	-10000	0	-10000	0	0
IL2	0.001	0.003	-10000	0	-10000	0	0
PIK3CA	0.011	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.02	0.021	-10000	0	-0.084	1	1
LCK	0.007	0.005	-10000	0	-10000	0	0
BCL2	0.012	0.14	0.38	3	-10000	0	3

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.009	0.003	-9999	-10000	0	0
GPC2	0.009	0.003	-9999	-10000	0	0
GPC2/Midkine	-0.003	0.049	-9999	-0.14	9	9
neuron projection morphogenesis	-0.003	0.049	-9999	-0.14	9	9

×

IL2 signaling events mediated by STAT5

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
GAB2	0.01	0	-10000	0	-10000	0	0
ELF1	-0.004	0.063	-10000	0	-0.25	5	5
CCNA2	0.009	0.003	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
JAK3	0.01	0.003	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.01	0	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.051	0.11	-10000	0	-0.32	9	9
SHC1	0.01	0	-10000	0	-10000	0	0
SP1	-0.042	0.11	-10000	0	-0.25	17	17
IL2RA	0.011	0.15	0.34	8	-0.45	5	13
IL2RB	0.008	0.004	-10000	0	-10000	0	0
SOS1	0.01	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.005	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.12	0.22	-10000	0	-0.45	23	23
PTPN11	0.01	0	-10000	0	-10000	0	0
CCND2	-0.09	0.19	-10000	0	-0.45	17	17
LCK	0.006	0.005	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
IL2	0.001	0.002	-10000	0	-10000	0	0
CDK6	0.01	0.001	-10000	0	-10000	0	0
CCND3	0.001	0.16	0.33	7	-0.34	4	11

×

TCGA08_retinoblastoma

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
CDKN2B	0.001	0.02	-10000	0	-0.037	17	17
CDKN2C	0.011	0.008	-10000	0	-0.042	1	1
CDKN2A	0.012	0.006	-10000	0	-0.013	1	1
CCND2	-0.001	0.018	0.13	1	-0.098	1	2
RB1	-0.003	0.036	0.11	1	-0.21	2	3
CDK4	0.003	0.037	0.21	2	-0.12	1	3
CDK6	0.003	0.038	0.22	2	-0.11	1	3
G1/S progression	0.003	0.036	0.21	2	-0.11	1	3

×

Regulation of Androgen receptor activity

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
HDAC1	-0.004	0.008	0.028	4	-0.016	4	8
SMARCC1	0.003	0.008	-10000	0	-10000	0	0
REL	0.008	0.011	0.029	3	-0.044	3	6
HDAC7	-0.001	0.072	0.26	4	-0.21	1	5
JUN	0.01	0.007	0.031	4	-0.009	4	8
EP300	0.01	0.001	0.017	1	-10000	0	1
KAT2B	0.01	0.003	0.017	1	-10000	0	1
KAT5	0.009	0.005	-10000	0	-0.011	4	4
MAPK14	0.001	0.023	0.066	8	-10000	0	8
FOXO1	0.01	0.005	0.019	4	-0.01	4	8
T-DHT/AR	0.023	0.086	0.33	4	-0.21	1	5
MAP2K6	0.012	0.01	0.038	8	-10000	0	8
BRM/BAF57	0.016	0.018	0.08	4	-10000	0	4
MAP2K4	0.012	0.01	0.038	8	-10000	0	8
SMARCA2	0.01	0.01	0.04	4	-0.024	4	8
PDE9A	0.004	0.007	-10000	0	-10000	0	0
NCOA2	0.011	0.007	0.035	5	-10000	0	5
CEBPA	0.009	0.006	-10000	0	-0.017	4	4
EHMT2	0.01	0.007	0.034	4	-0.011	4	8
cell proliferation	0.017	0.11	0.31	8	-0.28	1	9
NR0B1	0.005	0.005	-10000	0	-10000	0	0
EGR1	0.009	0.009	0.043	3	-0.022	2	5
RXRs/9cRA	0.007	0.04	0.077	4	-0.094	9	13
AR/RACK1/Src	0.012	0.11	0.36	6	-0.21	1	7
AR/GR	0	0.049	0.14	1	-0.16	4	5
GNB2L1	0.011	0.004	0.026	6	-10000	0	6
PKN1	0.01	0.001	0.017	1	-10000	0	1
RCHY1	0.01	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0.001	0.005	0.02	6	-10000	0	6
MAPK8	0	0.02	0.062	7	-10000	0	7
T-DHT/AR/TIF2/CARM1	0.015	0.096	0.32	5	-0.23	2	7
SRC	0.003	0.043	0.15	5	-10000	0	5
NR3C1	0.01	0.001	-10000	0	-10000	0	0
KLK3	-0.021	0.26	0.56	4	-1	4	8
APPBP2	0.012	0.006	0.037	4	-10000	0	4
TRIM24	0.01	0.011	0.046	4	-0.022	4	8
T-DHT/AR/TIP60	-0.008	0.05	0.15	3	-0.22	1	4
TMPRSS2	0.021	0.086	0.46	3	-10000	0	3
RXRG	0.008	0.006	0.018	1	-0.011	3	4
mol:9cRA	0	0.002	-10000	0	-10000	0	0
RXRA	0.01	0.005	0.018	1	-0.011	4	5
RXRB	0.01	0.005	0.018	1	-0.011	4	5
CARM1	0.012	0.005	0.03	6	-10000	0	6
NR2C2	0.01	0.005	0.019	4	-0.01	4	8
KLK2	-0.017	0.052	-10000	0	-0.25	2	2
AR	0.002	0.045	0.18	1	-0.18	3	4
SENP1	0.01	0.005	0.02	4	-0.012	4	8
HSP90AA1	0.01	0	-10000	0	-10000	0	0
MDM2	0.008	0.017	0.038	4	-0.06	4	8
SRY	-0.001	0.014	-10000	0	-0.055	4	4
GATA2	0.01	0.001	-10000	0	-10000	0	0
MYST2	0.009	0.006	-10000	0	-0.017	4	4
HOXB13	0.004	0.015	0.072	3	-0.038	2	5
T-DHT/AR/RACK1/Src	0	0.073	0.24	5	-0.21	1	6
positive regulation of transcription	0.01	0.001	-10000	0	-10000	0	0
DNAJA1	0.012	0.006	0.037	4	-10000	0	4
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.004	-10000	0	-10000	0	0
NCOA1	0.012	0.011	-10000	0	-10000	0	0
SPDEF	0.01	0.014	0.071	3	-0.024	3	6
T-DHT/AR/TIF2	-0.007	0.076	0.17	3	-0.23	4	7
T-DHT/AR/Hsp90	-0.005	0.056	0.14	5	-0.22	1	6
GSK3B	0.011	0.006	0.029	4	-0.008	3	7
NR2C1	0.009	0.008	-10000	0	-0.028	3	3
mol:T-DHT	0.003	0.039	0.13	5	-10000	0	5
SIRT1	0.01	0.001	0.017	1	-10000	0	1
ZMIZ2	0.008	0.019	0.042	3	-0.069	4	7
POU2F1	0.023	0.046	0.22	4	-10000	0	4
T-DHT/AR/DAX-1	-0.006	0.053	0.16	3	-0.22	1	4
CREBBP	0.01	0.001	0.017	1	-10000	0	1
SMARCE1	0.01	0.01	0.04	4	-0.024	4	8

×

BARD1 signaling events

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
BARD1/CSTF1	0.003	0.039	-10000	0	-0.12	7	7
ATM	0.01	0.002	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0.001	-10000	0	-10000	0	0
ATR	0.01	0.002	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.002	0.031	-10000	0	-0.19	2	2
protein ubiquitination	0.013	0.043	-10000	0	-0.1	9	9
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0.017	0.027	-10000	0	-0.15	2	2
MRE11A	0.01	0.002	-10000	0	-10000	0	0
DNA-PK	0.021	0.002	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.001	0.038	-10000	0	-0.21	2	2
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.01	0	-10000	0	-10000	0	0
CCNE1	0.01	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.015	0	-10000	0	-10000	0	0
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.003	0.039	-10000	0	-0.12	7	7
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.012	0.046	-10000	0	-0.21	3	3
BRCA1/BARD1/ubiquitin	0.003	0.039	-10000	0	-0.12	7	7
BARD1/DNA-PK	0.016	0.034	-10000	0	-0.093	7	7
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.003	0.039	0.12	7	-10000	0	7
BRCA1/BARD1/CTIP/M/R/N Complex	-0.032	0.11	-10000	0	-0.29	9	9
BRCA1/BACH1/BARD1/TopBP1	0.007	0.042	-10000	0	-0.11	8	8
BRCA1/BARD1/P53	0.013	0.04	-10000	0	-0.1	8	8
BARD1/CSTF1/BRCA1	0.01	0.035	-10000	0	-0.1	7	7
BRCA1/BACH1	0.01	0	-10000	0	-10000	0	0
BARD1	0.009	0.003	-10000	0	-10000	0	0
PCNA	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.01	0.035	-10000	0	-0.1	7	7
BRCA1/BARD1/UbcH7	0.01	0.035	-10000	0	-0.1	7	7
BRCA1/BARD1/RAD51/PCNA	0.015	0.036	-10000	0	-0.093	8	8
BARD1/DNA-PK/P53	0.02	0.034	-10000	0	-0.088	7	7
BRCA1/BARD1/Ubiquitin	0.003	0.039	-10000	0	-0.12	7	7
BRCA1/BARD1/CTIP	-0.009	0.057	-10000	0	-0.13	14	14
FA complex	0.006	0.022	-10000	0	-0.13	2	2
BARD1/EWS	0.003	0.039	-10000	0	-0.12	7	7
RBBP8	-0.005	0.002	-10000	0	-10000	0	0
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0.002	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.013	0.039	0.1	8	-10000	0	8
BRCA1/BARD1	0.015	0.044	-10000	0	-0.1	9	9
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.036	-10000	0	-0.12	7	7
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.01	0.001	-10000	0	-10000	0	0
RAD50	0.01	0.001	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.003	0.039	-10000	0	-0.12	7	7
EWSR1	0.01	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.01	0	-10000	0	-10000	0	0
VLDLR	0.01	0	-10000	0	-10000	0	0
LRPAP1	0.01	0	-10000	0	-10000	0	0
NUDC	0.01	0	-10000	0	-10000	0	0
RELN/LRP8	0.001	0.04	-10000	0	-0.1	10	10
CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
KATNA1	0.01	0.001	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.009	0.067	0.14	15	-0.093	10	25
IQGAP1/CaM	0.008	0.03	-10000	0	-0.12	4	4
DAB1	0.003	0.005	-10000	0	-10000	0	0
IQGAP1	0.01	0.002	-10000	0	-10000	0	0
PLA2G7	0.006	0.005	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.015	0.003	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.01	0	-10000	0	-10000	0	0
CDK5R1	0.01	0	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.004	0	-10000	0	-10000	0	0
CDK5R2	0.008	0.004	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.005	0.041	-10000	0	-0.1	12	12
YWHAE	0.01	0	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.01	0.083	0.15	15	-0.14	6	21
MAP1B	0.002	0.001	-10000	0	-10000	0	0
RAC1	0.004	0.001	-10000	0	-10000	0	0
p35/CDK5	0.007	0.062	0.13	15	-10000	0	15
RELN	0.006	0.005	-10000	0	-10000	0	0
PAFAH/LIS1	0.006	0.005	-10000	0	-10000	0	0
LIS1/CLIP170	0.01	0	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.022	0.038	-10000	0	-0.13	6	6
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.019	0.054	-10000	0	-0.14	14	14
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.008	0.064	0.12	9	-0.15	6	15
LIS1/IQGAP1	0.01	0.002	-10000	0	-10000	0	0
RHOA	0.004	0.001	-10000	0	-10000	0	0
PAFAH1B1	-0.006	0	-10000	0	-10000	0	0
PAFAH1B3	0.01	0	-10000	0	-10000	0	0
PAFAH1B2	0.01	0.002	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.016	0.024	-10000	0	-0.11	1	1
NDEL1/Katanin 60/Dynein heavy chain	0.004	0.062	0.12	8	-0.14	6	14
LRP8	0.01	0.002	-10000	0	-10000	0	0
NDEL1/Katanin 60	0.008	0.082	0.15	14	-0.14	6	20
P39/CDK5	-0.004	0.056	0.13	9	-0.16	2	11
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.01	0	-10000	0	-10000	0	0
CDK5	0.008	0.065	0.13	15	-0.087	10	25
PPP2R5D	0.01	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.009	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.002	0.036	-10000	0	-0.087	12	12
RELN/VLDLR	0.006	0.039	-10000	0	-0.093	10	10
CDC42	0.004	0.001	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.01	0.002	-9999	-10000	0	0
ITGA4	0.007	0.005	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.043	-9999	-0.12	9	9
alpha4/beta1 Integrin	0.002	0.036	-9999	-0.12	6	6

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.01	0	-10000	0	-10000	0	0
LAT2	0.005	0.036	-10000	0	-0.13	3	3
AP1	-0.006	0.11	-10000	0	-0.3	8	8
mol:PIP3	0.023	0.13	0.34	7	-0.26	3	10
IKBKB	0.02	0.087	0.28	5	-0.2	2	7
AKT1	0.005	0.044	0.1	12	-10000	0	12
IKBKG	0.02	0.087	0.28	5	-0.2	2	7
MS4A2	0.002	0.006	0.033	1	-0.009	3	4
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
MAP3K1	0.005	0.076	0.21	2	-0.27	3	5
mol:Ca2+	0.023	0.11	0.31	7	-0.21	3	10
LYN	0.011	0.003	0.021	1	-0.009	1	2
CBLB	0.004	0.034	-10000	0	-0.13	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.018	0.012	-10000	0	-0.091	1	1
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.009	0.003	-10000	0	-10000	0	0
PLD2	0.013	0.048	0.12	13	-10000	0	13
PTPN13	0.01	0.055	-10000	0	-10000	0	0
PTPN11	0.011	0.006	-10000	0	-0.015	3	3
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.012	0.047	0.2	2	-10000	0	2
SYK	0.01	0.004	0.021	1	-0.009	1	2
GRB2	0.01	0.001	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.015	0.064	-10000	0	-0.23	5	5
LAT	0.004	0.048	0.16	2	-0.18	3	5
PAK2	0.007	0.082	0.22	2	-0.3	3	5
NFATC2	-0.019	0.083	-10000	0	-0.34	5	5
HRAS	0.008	0.087	0.23	2	-0.32	3	5
GAB2	0.01	0	-10000	0	-10000	0	0
PLA2G1B	0.002	0.02	-10000	0	-10000	0	0
Fc epsilon R1	0.01	0.014	-10000	0	-0.081	1	1
Antigen/IgE/Fc epsilon R1	0.01	0.014	-10000	0	-0.068	1	1
mol:GDP	0.008	0.1	0.21	3	-0.4	3	6
JUN	0.01	0.002	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
FOS	0.009	0.003	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK	0.008	0.037	-10000	0	-0.14	3	3
CHUK	0.02	0.087	0.28	5	-0.2	2	7
KLRG1	0.006	0.033	-10000	0	-0.12	3	3
VAV1	0.011	0.042	0.14	3	-0.14	2	5
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	0.005	0.035	-10000	0	-0.13	3	3
negative regulation of mast cell degranulation	0.012	0.039	-10000	0	-0.14	3	3
BTK	-0.004	0.11	-10000	0	-0.52	3	3
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.012	0.064	-10000	0	-0.18	9	9
GAB2/PI3K/SHP2	-0.01	0.012	-10000	0	-0.086	1	1
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	0.01	0.037	-10000	0	-0.13	3	3
RAF1	0.005	0.017	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	0.001	0.042	-10000	0	-0.1	10	10
FCER1G	0.009	0.005	-10000	0	-0.012	3	3
FCER1A	0.006	0.006	0.024	1	-0.009	1	2
Antigen/IgE/Fc epsilon R1/Fyn	0.015	0.014	-10000	0	-0.064	1	1
MAPK3	0.004	0.015	-10000	0	-10000	0	0
MAPK1	0.004	0.015	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.009	0.12	-10000	0	-0.54	4	4
DUSP1	0.01	0.001	-10000	0	-10000	0	0
NF-kappa-B/RelA	0.004	0.031	-10000	0	-0.1	3	3
actin cytoskeleton reorganization	0.019	0.047	-10000	0	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.014	0.068	0.15	5	-0.27	2	7
FER	0.005	0.035	-10000	0	-0.13	3	3
RELA	0.01	0	-10000	0	-10000	0	0
ITK	-0.014	0.092	0.11	10	-0.25	9	19
SOS1	0.01	0.001	-10000	0	-10000	0	0
PLCG1	0.009	0.099	0.19	6	-0.36	3	9
cytokine secretion	-0.002	0.02	-10000	0	-0.07	4	4
SPHK1	0.003	0.034	-10000	0	-0.13	3	3
PTK2	0.019	0.048	-10000	0	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.008	0.057	-10000	0	-0.22	4	4
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.023	0.11	0.32	6	-0.3	2	8
MAP2K2	0.003	0.015	-10000	0	-10000	0	0
MAP2K1	0.003	0.015	-10000	0	-10000	0	0
MAP2K7	0.01	0	-10000	0	-10000	0	0
KLRG1/SHP2	0.01	0.032	-10000	0	-0.12	2	2
MAP2K4	0.015	0.006	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB	0.002	0.037	-10000	0	-0.1	8	8
mol:Choline	0.013	0.048	0.12	13	-10000	0	13
SHC/Grb2/SOS1	0.025	0.04	-10000	0	-0.16	1	1
FYN	0.01	0	-10000	0	-10000	0	0
DOK1	0.01	0	-10000	0	-10000	0	0
PXN	0.017	0.046	-10000	0	-10000	0	0
HCLS1	0.01	0.045	0.16	3	-0.13	3	6
PRKCB	0.022	0.1	0.28	6	-0.22	3	9
FCGR2B	0.008	0.004	-10000	0	-10000	0	0
IGHE	0	0.003	0.012	2	-10000	0	2
KLRG1/SHIP	0.012	0.039	-10000	0	-0.14	3	3
LCP2	0.009	0.003	-10000	0	-10000	0	0
PLA2G4A	0.004	0.039	-10000	0	-0.16	3	3
RASA1	0.01	0.001	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.013	0.048	0.12	13	-10000	0	13
IKK complex	0.018	0.076	0.25	5	-0.2	1	6
WIPF1	0.01	0.002	-10000	0	-10000	0	0

×

PLK1 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
regulation of centriole-centriole cohesion	0.004	0.044	0.18	4	-0.098	3	7
BUB1B	-0.018	0.064	-10000	0	-0.23	6	6
PLK1	-0.006	0.024	-10000	0	-0.094	5	5
PLK1S1	-0.001	0.012	-10000	0	-10000	0	0
KIF2A	-0.008	0.022	-10000	0	-0.092	4	4
regulation of mitotic centrosome separation	-0.006	0.024	-10000	0	-0.093	5	5
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.006	0.045	-10000	0	-0.11	11	11
WEE1	-0.017	0.075	-10000	0	-0.28	5	5
cytokinesis	-0.018	0.074	0.12	1	-0.27	6	7
PP2A-alpha B56	-0.054	0.2	-10000	0	-0.58	10	10
AURKA	-0.004	0.032	-10000	0	-0.16	2	2
PICH/PLK1	-0.008	0.036	-10000	0	-0.12	6	6
CENPE	-0.004	0.06	0.16	6	-0.12	9	15
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.022	-10000	0	-0.092	4	4
PPP2CA	0.01	0.001	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	-0.01	0.049	-10000	0	-0.25	3	3
PAK1	0.01	0.001	-10000	0	-10000	0	0
SPC24	0.01	0.002	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.03	0.092	0.074	3	-0.27	10	13
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	0	0.003	0.007	2	-0.012	4	6
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.004	0.012	-10000	0	-0.048	5	5
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-0.008	1	1
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.009	-10000	0	-10000	0	0
spindle elongation	-0.006	0.024	-10000	0	-0.093	5	5
ODF2	0.01	0.003	-10000	0	-0.013	1	1
BUB1	-0.068	0.21	-10000	0	-0.62	10	10
TPT1	-0.001	0.012	-10000	0	-10000	0	0
CDC25C	-0.019	0.083	-10000	0	-0.33	5	5
CDC25B	0.01	0.004	-10000	0	-0.018	1	1
SGOL1	-0.004	0.044	0.098	3	-0.18	4	7
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.003	0.054	-10000	0	-0.17	7	7
CDC14B	-0.003	0.002	0.004	2	-0.008	1	3
CDC20	0.009	0.003	-10000	0	-10000	0	0
PLK1/PBIP1	-0.014	0.035	-10000	0	-0.088	13	13
mitosis	-0.001	0.003	0.019	1	-10000	0	1
FBXO5	-0.01	0.028	-10000	0	-0.094	7	7
CDC2	0	0.003	-10000	0	-0.012	4	4
NDC80	0.009	0.004	-10000	0	-10000	0	0
metaphase plate congression	-0.001	0.016	-10000	0	-10000	0	0
ERCC6L	-0.01	0.05	-10000	0	-0.16	7	7
NLP/gamma Tubulin	-0.003	0.014	-10000	0	-0.054	5	5
microtubule cytoskeleton organization	-0.001	0.012	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.01	0.003	-10000	0	-0.01	1	1
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0	0.04	-10000	0	-0.11	8	8
GRASP65/GM130/RAB1/GTP/PLK1	0.01	0.026	-10000	0	-0.078	5	5
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.006	0.023	-10000	0	-0.12	2	2
mitotic prometaphase	-0.001	0.002	-10000	0	-0.008	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.021	-10000	0	-0.13	1	1
microtubule-based process	-0.001	0.033	-10000	0	-0.13	4	4
Golgi organization	-0.006	0.024	-10000	0	-0.093	5	5
Cohesin/SA2	0	0.024	-10000	0	-0.087	5	5
PPP1CB/MYPT1	0.015	0.004	-10000	0	-10000	0	0
KIF20A	0.009	0.003	-10000	0	-10000	0	0
APC/C/CDC20	0	0.029	-10000	0	-0.11	4	4
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.014	0.034	-10000	0	-0.087	13	13
PRC1	0.01	0	-10000	0	-10000	0	0
ECT2	-0.01	0.026	-10000	0	-0.095	6	6
C13orf34	-0.007	0.023	-10000	0	-0.091	4	4
NUDC	-0.001	0.016	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.018	0.064	-10000	0	-0.23	6	6
spindle assembly	-0.006	0.019	-10000	0	-0.075	5	5
spindle stabilization	-0.001	0.012	-10000	0	-10000	0	0
APC/C/HCDH1	0.009	0.002	-10000	0	-10000	0	0
MKLP2/PLK1	-0.001	0.033	-10000	0	-0.13	4	4
CCNB1	0.009	0.005	-10000	0	-0.017	3	3
PPP1CB	0.01	0.002	-10000	0	-0.01	1	1
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	0	0.016	-10000	0	-10000	0	0
TUBG1	-0.001	0.012	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.014	0.049	-10000	0	-0.17	7	7
MLF1IP	-0.003	0.002	0.004	2	-0.01	3	5
INCENP	0.008	0.007	-10000	0	-0.01	10	10

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.006	0.048	-10000	0	-0.1	15	15
alphaM/beta2 Integrin/GPIbA	0.015	0.017	-10000	0	-0.1	1	1
alphaM/beta2 Integrin/proMMP-9	-0.002	0.044	-10000	0	-0.1	12	12
PLAUR	0.01	0.001	-10000	0	-10000	0	0
HMGB1	0.016	0.024	0.084	7	-0.044	1	8
alphaM/beta2 Integrin/Talin	0.017	0.017	-10000	0	-0.1	1	1
AGER	0.016	0.024	0.084	7	-0.044	1	8
RAP1A	0.01	0	-10000	0	-10000	0	0
SELPLG	0.01	0.002	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.019	0.034	-10000	0	-0.14	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.007	0.005	-10000	0	-10000	0	0
CYR61	0.009	0.003	-10000	0	-10000	0	0
TLN1	0.01	0	-10000	0	-10000	0	0
Rap1/GTP	-0.029	0.087	-10000	0	-0.24	7	7
RHOA	0.01	0	-10000	0	-10000	0	0
P-selectin oligomer	0.009	0.003	-10000	0	-10000	0	0
MYH2	-0.031	0.12	0.17	4	-0.21	16	20
MST1R	0.009	0.003	-10000	0	-10000	0	0
leukocyte activation during inflammatory response	0.003	0.029	-10000	0	-0.084	7	7
APOB	0.006	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.008	0.004	-10000	0	-10000	0	0
JAM3	0.01	0.002	-10000	0	-10000	0	0
GP1BA	0.008	0.004	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	0.017	0.017	-10000	0	-0.1	1	1
alphaM/beta2 Integrin	-0.031	0.1	0.13	4	-0.27	7	11
JAM3 homodimer	0.01	0.002	-10000	0	-10000	0	0
ICAM2	0.01	0.002	-10000	0	-10000	0	0
ICAM1	0.01	0	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.031	0.1	0.14	2	-0.27	7	9
cell adhesion	0.015	0.017	-10000	0	-0.1	1	1
NFKB1	-0.013	0.038	0.13	1	-0.21	2	3
THY1	0.01	0.002	-10000	0	-10000	0	0
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
Lipoprotein(a)	-0.005	0.031	-10000	0	-0.098	8	8
alphaM/beta2 Integrin/LRP/tPA	0.026	0.03	0.11	4	-0.11	2	6
IL6	0.016	0.14	0.55	4	-0.24	1	5
ITGB2	0.012	0.014	0.066	4	-0.044	1	5
elevation of cytosolic calcium ion concentration	0.022	0.029	0.1	3	-0.092	3	6
alphaM/beta2 Integrin/JAM2/JAM3	0.022	0.034	0.11	4	-0.093	4	8
JAM2	0.01	0.001	-10000	0	-10000	0	0
alphaM/beta2 Integrin/ICAM1	0.026	0.029	0.11	4	-0.088	2	6
alphaM/beta2 Integrin/uPA/Plg	0.018	0.03	0.1	4	-0.092	3	7
RhoA/GTP	-0.051	0.11	-10000	0	-0.21	19	19
positive regulation of phagocytosis	-0.02	0.076	0.13	1	-0.2	7	8
Ron/MSP	0.012	0.016	-10000	0	-0.12	1	1
alphaM/beta2 Integrin/uPAR/uPA	0.023	0.03	0.11	3	-0.093	3	6
alphaM/beta2 Integrin/uPAR	0.017	0.017	-10000	0	-0.1	1	1
PLAU	0.01	0.002	-10000	0	-10000	0	0
PLAT	0.01	0	-10000	0	-10000	0	0
actin filament polymerization	-0.027	0.12	0.16	5	-0.24	11	16
MST1	0.01	0.002	-10000	0	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.008	0.034	0.095	3	-0.085	7	10
TNF	0.01	0.13	0.49	4	-0.46	1	5
RAP1B	0.01	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.013	0.025	-10000	0	-0.1	3	3
fibrinolysis	0.012	0.023	-10000	0	-0.091	3	3
HCK	0.01	0.002	-10000	0	-10000	0	0
dendritic cell antigen processing and presentation	-0.031	0.1	0.14	2	-0.27	7	9
VTN	0.007	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	0.01	0.034	-10000	0	-0.12	4	4
LPA	0.001	0.003	-10000	0	-10000	0	0
LRP1	0.01	0.001	-10000	0	-10000	0	0
cell migration	-0.022	0.059	-10000	0	-0.12	20	20
FN1	0.009	0.003	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Thy1	0.013	0.025	-10000	0	-0.1	3	3
MPO	0.009	0.004	-10000	0	-10000	0	0
KNG1	0.001	0.004	-10000	0	-10000	0	0
RAP1/GDP	0.014	0	-10000	0	-10000	0	0
ROCK1	-0.03	0.12	0.16	5	-0.22	15	20
ELA2	0	0	-10000	0	-10000	0	0
PLG	0	0.002	-10000	0	-10000	0	0
CTGF	0.01	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Hck	0.015	0.022	-10000	0	-0.1	2	2
ITGAM	0.016	0.024	0.084	7	-0.044	1	8
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.019	0.035	0.11	3	-0.093	5	8
HP	0.004	0.005	-10000	0	-10000	0	0
leukocyte adhesion	0.005	0.042	-10000	0	-0.14	4	4
SELP	0.009	0.003	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.013	0.053	-10000	0	-0.16	9	9
CRKL	0.01	0	-10000	0	-10000	0	0
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
ITGA4	0.007	0.005	-10000	0	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.009	0.033	-10000	0	-0.092	7	7
EPO	0.007	0.005	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.043	-10000	0	-0.12	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.002	0.036	-10000	0	-0.12	6	6
EPO/EPOR (dimer)	0.012	0.005	-10000	0	-10000	0	0
lamellipodium assembly	0.004	0.024	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PI3K	0.012	0.022	-10000	0	-0.12	2	2
ARF6	0.01	0	-10000	0	-10000	0	0
JAK2	-0.004	0.036	-10000	0	-0.13	6	6
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
MADCAM1	0.008	0.004	-10000	0	-10000	0	0
cell adhesion	0.008	0.033	-10000	0	-0.092	7	7
CRKL/CBL	0.015	0	-10000	0	-10000	0	0
ITGB1	0.01	0	-10000	0	-10000	0	0
SRC	0.021	0.1	0.21	15	-0.11	9	24
ITGB7	0.01	0.002	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0	0.046	-10000	0	-0.12	9	9
p130Cas/Crk/Dock1	0.018	0.091	0.19	15	-0.15	2	17
VCAM1	0.008	0.004	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.013	0.032	-10000	0	-0.093	6	6
BCAR1	0.021	0.099	0.21	15	-0.1	9	24
EPOR	0.01	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.01	0	-10000	0	-10000	0	0
GIT1	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.004	0.025	-10000	0	-10000	0	0

×

IL1-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.01	0.004	-9999	-10000	0	0
PRKCZ	0.01	0.002	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.001	0.021	-9999	-10000	0	0
IRAK/TOLLIP	0.011	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
IKBKG	0.01	0	-9999	-10000	0	0
IL1 alpha/IL1R2	0.001	0.029	-9999	-0.12	4	4
IL1A	0.003	0.005	-9999	-10000	0	0
IL1B	-0.004	0.002	-9999	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0.021	0.021	-9999	-0.084	3	3
IL1R2	0.008	0.005	-9999	-10000	0	0
IL1R1	0.009	0.004	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.012	0.066	-9999	-0.17	9	9
TOLLIP	0.01	0	-9999	-10000	0	0
TICAM2	0.01	0.002	-9999	-10000	0	0
MAP3K3	0.01	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.002	0.023	-9999	-0.098	4	4
IKK complex/ELKS	0.007	0.011	-9999	-10000	0	0
JUN	-0.013	0.019	-9999	-0.14	1	1
MAP3K7	0.01	0.002	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.001	0.045	-9999	-0.085	17	17
IL1 alpha/IL1R1/IL1RAP/MYD88	0.009	0.036	-9999	-0.091	9	9
PIK3R1	0.01	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.013	0.036	-9999	-0.086	9	9
IL1 beta fragment/IL1R1/IL1RAP	-0.006	0.042	-9999	-0.092	15	15
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.012	0.02	-9999	-0.094	4	4
IRAK1	-0.005	0.001	-9999	-10000	0	0
IL1RN/IL1R1	-0.017	0.062	-9999	-0.14	16	16
IRAK4	0.01	0	-9999	-10000	0	0
PRKCI	0.01	0.001	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
PI3K	0.012	0.022	-9999	-0.12	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.057	-9999	-0.14	9	9
CHUK	0.01	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.006	0.042	-9999	-0.092	15	15
IL1 beta/IL1R2	-0.005	0.039	-9999	-0.1	11	11
IRAK/TRAF6/TAK1/TAB1/TAB2	0.01	0.02	-9999	-0.079	4	4
NF kappa B1 p50/RelA	-0.004	0.041	-9999	-0.082	17	17
IRAK3	0.01	0.002	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0	0.046	-9999	-0.09	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.048	-9999	-0.14	9	9
IL1 alpha/IL1R1/IL1RAP	0.003	0.037	-9999	-0.1	9	9
RELA	0.01	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.01	0	-9999	-10000	0	0
MYD88	0.01	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.017	0	-9999	-10000	0	0
IL1RAP	0.01	0	-9999	-10000	0	0
UBE2N	0.01	0	-9999	-10000	0	0
IRAK/TRAF6	-0.015	0.037	-9999	-0.094	5	5
CASP1	0.009	0.004	-9999	-10000	0	0
IL1RN/IL1R2	-0.012	0.054	-9999	-0.13	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.002	0.042	-9999	-0.087	15	15
TMEM189-UBE2V1	0.004	0.005	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.019	0.08	-9999	-0.24	9	9
PIK3CA	0.01	0.002	-9999	-10000	0	0
IL1RN	0.008	0.004	-9999	-10000	0	0
TRAF6/TAK1/TAB1/TAB2	0.012	0.021	-9999	-0.08	4	4
MAP2K6	-0.01	0.016	-9999	-0.078	4	4

×

HIF-2-alpha transcription factor network

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
MMP14	0.002	0.015	-10000	0	-10000	0	0
oxygen homeostasis	0.013	0.035	0.14	4	-10000	0	4
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.01	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.032	0.083	0.19	12	-10000	0	12
EPO	0.082	0.24	0.87	4	-10000	0	4
FIH (dimer)	0.022	0.037	0.15	4	-10000	0	4
APEX1	0.02	0.03	0.13	3	-10000	0	3
SERPINE1	0.037	0.21	0.73	2	-0.42	1	3
FLT1	-0.012	0.09	-10000	0	-0.57	2	2
ADORA2A	0.073	0.24	0.8	4	-10000	0	4
germ cell development	0.072	0.24	0.79	4	-10000	0	4
SLC11A2	0.072	0.24	0.8	4	-10000	0	4
BHLHE40	0.072	0.24	0.8	4	-10000	0	4
HIF1AN	0.022	0.037	0.15	4	-10000	0	4
HIF2A/ARNT/SIRT1	0.069	0.17	0.35	17	-10000	0	17
ETS1	0.023	0.063	0.42	2	-10000	0	2
CITED2	0.001	0.014	-10000	0	-10000	0	0
KDR	-0.012	0.09	-10000	0	-0.57	2	2
PGK1	0.072	0.24	0.8	4	-10000	0	4
SIRT1	0.012	0.007	0.037	5	-10000	0	5
response to hypoxia	0.002	0.007	0.026	5	-10000	0	5
HIF2A/ARNT	0.11	0.22	0.89	2	-10000	0	2
EPAS1	0.055	0.17	0.62	4	-10000	0	4
SP1	0.012	0	-10000	0	-10000	0	0
ABCG2	0.071	0.24	0.8	4	-10000	0	4
EFNA1	0.072	0.24	0.8	4	-10000	0	4
FXN	0.073	0.24	0.8	4	-10000	0	4
POU5F1	0.072	0.24	0.79	4	-10000	0	4
neuron apoptosis	-0.1	0.22	-10000	0	-0.88	2	2
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	0.021	0.037	0.15	4	-10000	0	4
EGLN2	0.021	0.037	0.15	4	-10000	0	4
EGLN1	0.022	0.037	0.15	4	-10000	0	4
VHL/Elongin B/Elongin C	0.021	0	-10000	0	-10000	0	0
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.02	0.03	0.13	3	-10000	0	3
SLC2A1	0.073	0.24	0.8	4	-10000	0	4
TWIST1	0.026	0.24	0.87	4	-0.41	2	6
ELK1	0.012	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.062	0.14	0.32	14	-10000	0	14
VEGFA	0.052	0.22	0.73	3	-0.42	1	4
CREBBP	0.01	0	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.002	0.003	-10000	0	-10000	0	0
RFC1	-0.002	0.003	-10000	0	-10000	0	0
PRKDC	0	0.018	0.16	1	-10000	0	1
RIPK1	0.008	0.01	-10000	0	-0.034	4	4
CASP7	0.011	0.048	0.17	5	-10000	0	5
FASLG/FAS/FADD/FAF1	-0.006	0.048	0.14	2	-0.15	6	8
MAP2K4	0.013	0.098	0.36	3	-0.18	5	8
mol:ceramide	0.003	0.085	0.32	3	-0.17	8	11
GSN	-0.002	0.003	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.013	0.076	0.19	4	-0.18	6	10
FAS	0.011	0.009	0.046	4	-10000	0	4
BID	0.003	0.051	0.22	4	-10000	0	4
MAP3K1	0.018	0.069	0.26	3	-10000	0	3
MAP3K7	0.011	0.004	0.026	4	-10000	0	4
RB1	-0.002	0.003	-10000	0	-10000	0	0
CFLAR	0.008	0.01	-10000	0	-0.034	4	4
HGF/MET	-0.01	0.059	-10000	0	-0.12	17	17
ARHGDIB	0	0.02	0.18	1	-10000	0	1
FADD	0.012	0.008	0.046	4	-10000	0	4
actin filament polymerization	-0.005	0.032	-10000	0	-0.14	4	4
NFKB1	0.022	0.063	0.32	3	-10000	0	3
MAPK8	0.013	0.11	0.42	3	-10000	0	3
DFFA	-0.002	0.003	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.005	0.032	0.14	4	-10000	0	4
FAS/FADD/MET	0.015	0.033	0.075	3	-0.1	5	8
CFLAR/RIP1	0.012	0.015	-10000	0	-0.059	2	2
FAIM3	0.008	0.005	-10000	0	-0.012	4	4
FAF1	0.013	0.012	0.061	4	-10000	0	4
PARP1	-0.002	0.003	-10000	0	-10000	0	0
DFFB	-0.002	0.003	-10000	0	-10000	0	0
CHUK	0.017	0.054	0.27	3	-10000	0	3
FASLG	0.006	0.008	0.06	1	-10000	0	1
FAS/FADD	0.014	0.025	0.075	3	-0.12	2	5
HGF	0.008	0.004	-10000	0	-10000	0	0
LMNA	0.002	0.029	0.13	4	-10000	0	4
CASP6	-0.002	0.003	-10000	0	-10000	0	0
CASP10	0.011	0.007	0.043	3	-10000	0	3
CASP3	-0.001	0.004	-10000	0	-10000	0	0
PTPN13	0.009	0.004	-10000	0	-10000	0	0
CASP8	0.005	0.056	0.25	4	-10000	0	4
IL6	0.033	0.12	0.52	4	-10000	0	4
MET	0.01	0.002	-10000	0	-10000	0	0
ICAD/CAD	-0.005	0.01	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	0.002	0.085	0.32	3	-0.18	8	11
activation of caspase activity by cytochrome c	0.003	0.051	0.22	4	-10000	0	4
PAK2	-0.002	0.005	-10000	0	-10000	0	0
BCL2	0.009	0.004	-10000	0	-0.009	4	4

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.015	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.009	0.003	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.068	-9999	-0.13	15	15
NFKBIA	-0.01	0.073	-9999	-0.14	15	15
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.01	0	-9999	-10000	0	0
ARRB2	0.005	0	-9999	-10000	0	0
REL	0.009	0.003	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.01	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0.002	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.007	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
NFKB1	-0.006	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.012	0.073	-9999	-0.15	15	15
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.002	0.067	-9999	-0.13	15	15
SRC	0.01	0	-9999	-10000	0	0
PI3K	0.012	0.022	-9999	-0.12	2	2
NF kappa B1 p50/RelA	-0.012	0.074	-9999	-0.15	15	15
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.01	0.002	-9999	-10000	0	0
I kappa B alpha/PIK3R1	-0.005	0.071	-9999	-0.14	15	15
cell death	-0.002	0.065	-9999	-0.12	15	15
NF kappa B1 p105/c-Rel	0.009	0.003	-9999	-10000	0	0
LCK	0.006	0.005	-9999	-10000	0	0
BCL3	0.01	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.011	0.022	-10000	0	-0.12	2	2
alphaV beta3 Integrin	0.008	0.035	-10000	0	-0.1	7	7
PTK2	-0.003	0.1	0.25	5	-0.24	4	9
IGF1R	0.01	0	-10000	0	-10000	0	0
PI4KB	0.01	0	-10000	0	-10000	0	0
MFGE8	0.01	0.001	-10000	0	-10000	0	0
SRC	0.01	0	-10000	0	-10000	0	0
CDKN1B	-0.063	0.13	-10000	0	-0.3	17	17
VEGFA	0.01	0.002	-10000	0	-10000	0	0
ILK	-0.063	0.13	-10000	0	-0.3	17	17
ROCK1	0.01	0	-10000	0	-10000	0	0
AKT1	-0.061	0.12	-10000	0	-0.28	17	17
PTK2B	0.001	0.046	0.13	8	-0.088	4	12
alphaV/beta3 Integrin/JAM-A	-0.013	0.051	-10000	0	-0.095	21	21
CBL	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.013	0.014	-10000	0	-0.1	1	1
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.02	0.023	-10000	0	-0.093	3	3
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.016	0.075	-10000	0	-0.14	20	20
alphaV/beta3 Integrin/Syndecan-1	0.017	0.02	-10000	0	-0.1	2	2
PI4KA	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.002	0.046	-10000	0	-0.12	9	9
PI4 Kinase	0.015	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.011	0.047	-10000	0	-0.1	16	16
RPS6KB1	0.008	0.078	0.14	16	-0.17	3	19
TLN1	0.01	0	-10000	0	-10000	0	0
MAPK3	-0.033	0.11	-10000	0	-0.37	6	6
GPR124	0.01	0.002	-10000	0	-10000	0	0
MAPK1	-0.033	0.11	-10000	0	-0.37	6	6
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.012	0.027	-10000	0	-0.1	4	4
cell adhesion	0.014	0.016	-10000	0	-0.13	1	1
ANGPTL3	0.003	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.017	0.02	-10000	0	-0.1	2	2
IGF-1R heterotetramer	0.01	0	-10000	0	-10000	0	0
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
TGFBR2	0.01	0	-10000	0	-10000	0	0
ITGB3	0.01	0.002	-10000	0	-10000	0	0
IGF1	0.009	0.003	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.016	0.02	-10000	0	-0.1	2	2
apoptosis	0.01	0.001	-10000	0	-10000	0	0
CD47	0.01	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.017	0.02	-10000	0	-0.1	2	2
VCL	0.01	0.001	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.008	0.032	-10000	0	-0.1	6	6
CSF1	0.01	0	-10000	0	-10000	0	0
PIK3C2A	-0.077	0.14	-10000	0	-0.31	20	20
PI4 Kinase/Pyk2	-0.016	0.049	-10000	0	-0.096	20	20
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.018	0.027	-10000	0	-0.093	4	4
FAK1/Vinculin	0.001	0.095	0.21	6	-0.2	4	10
alphaV beta3/Integrin/ppsTEM5	0.016	0.02	-10000	0	-0.1	2	2
RHOA	0.01	0	-10000	0	-10000	0	0
VTN	0.007	0.005	-10000	0	-10000	0	0
BCAR1	0.01	0	-10000	0	-10000	0	0
FGF2	0.009	0.004	-10000	0	-10000	0	0
F11R	-0.005	0.002	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.017	0.02	-10000	0	-0.1	2	2
alphaV/beta3 Integrin/TGFBR2	0.017	0.02	-10000	0	-0.1	2	2
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.025	0.013	-10000	0	-0.093	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.016	0.018	-10000	0	-0.091	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.009	0.003	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Pyk2	0.017	0.034	0.13	4	-0.088	4	8
SDC1	0.01	0	-10000	0	-10000	0	0
VAV3	-0.009	0.009	-10000	0	-0.088	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
IRS1	0.01	0.001	-10000	0	-10000	0	0
FAK1/Paxillin	0.002	0.094	0.21	6	-0.2	4	10
cell migration	0	0.091	0.21	6	-0.18	4	10
ITGAV	0.01	0.001	-10000	0	-10000	0	0
PI3K	-0.012	0.051	-10000	0	-0.09	23	23
SPP1	0.005	0.005	-10000	0	-10000	0	0
KDR	0.01	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.001	-10000	0	-10000	0	0
COL4A3	0.008	0.004	-10000	0	-10000	0	0
angiogenesis	-0.033	0.13	0.19	1	-0.36	7	8
Rac1/GTP	-0.015	0.021	-10000	0	-0.082	7	7
EDIL3	0.007	0.005	-10000	0	-10000	0	0
cell proliferation	0.017	0.02	-10000	0	-0.1	2	2

×

Effects of Botulinum toxin

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
STX1A	-0.003	0	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.011	0.004	-10000	0	-10000	0	0
STXBP1	0.01	0	-10000	0	-10000	0	0
ACh/CHRNA1	0	0.027	0.041	10	-0.061	10	20
RAB3GAP2/RIMS1/UNC13B	0.014	0.019	-10000	0	-0.1	2	2
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	0.005	0.005	-10000	0	-10000	0	0
mol:ACh	-0.001	0.038	0.059	13	-0.079	11	24
RAB3GAP2	0.01	0.002	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.002	0.044	-10000	0	-0.1	11	11
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0	0.027	0.041	10	-0.061	10	20
UNC13B	0.01	0	-10000	0	-10000	0	0
CHRNA1	0.006	0.005	-10000	0	-10000	0	0
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.003	0.024	0.041	2	-0.06	11	13
SNAP25	0.001	0.001	-10000	0	-10000	0	0
VAMP2	0.001	0	-10000	0	-10000	0	0
SYT1	0.005	0.005	-10000	0	-10000	0	0
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.009	0	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.002	0.044	-10000	0	-0.1	11	11

×

Nongenotropic Androgen 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
PTK2	-0.003	0.001	0.004	2	-10000	0	2
GNB1/GNG2	0.011	0.027	-10000	0	-0.093	5	5
regulation of S phase of mitotic cell cycle	-0.002	0.038	-10000	0	-0.15	5	5
GNAO1	0.009	0.003	-10000	0	-10000	0	0
HRAS	0.009	0.006	0.018	2	-0.011	6	8
SHBG/T-DHT	0.007	0.001	-10000	0	-10000	0	0
PELP1	0.009	0.006	0.018	2	-0.011	6	8
AKT1	-0.002	0.001	0.003	5	-10000	0	5
MAP2K1	-0.014	0.051	0.21	2	-0.14	6	8
T-DHT/AR	0.001	0.025	-10000	0	-0.12	3	3
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.009	2	-0.007	6	8
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.01	0.002	-10000	0	-10000	0	0
mol:GDP	-0.014	0.049	-10000	0	-0.25	3	3
cell proliferation	-0.023	0.12	0.38	2	-0.38	6	8
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
FOS	-0.036	0.2	0.5	2	-0.68	6	8
mol:Ca2+	-0.001	0.011	0.042	2	-0.038	3	5
MAPK3	-0.018	0.088	0.31	2	-0.27	6	8
MAPK1	-0.006	0.069	0.27	2	-0.2	6	8
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	0.012	2	-0.004	6	8
cAMP biosynthetic process	0.003	0.03	0.18	2	-10000	0	2
GNG2	0.01	0.002	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	0.012	2	-0.004	6	8
HRAS/GTP	0.013	0.035	0.14	2	-0.074	8	10
actin cytoskeleton reorganization	0.013	0.015	-10000	0	-0.083	2	2
SRC	0.009	0.006	0.018	2	-0.011	6	8
voltage-gated calcium channel activity	0	0.002	0.012	2	-0.004	6	8
PI3K	0.011	0.018	-10000	0	-0.1	2	2
apoptosis	0.018	0.12	0.39	6	-0.39	2	8
T-DHT/AR/PELP1	0.007	0.024	-10000	0	-0.1	3	3
HRAS/GDP	-0.005	0.05	-10000	0	-0.21	4	4
CREB1	-0.03	0.11	-10000	0	-0.42	6	6
RAC1-CDC42/GTP	0.017	0.016	-10000	0	-0.084	2	2
AR	0.007	0.006	0.019	1	-0.01	5	6
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.012	0.041	0.18	2	-0.16	1	3
RAC1-CDC42/GDP	0.001	0.049	-10000	0	-0.23	3	3
T-DHT/AR/PELP1/Src	0.013	0.025	-10000	0	-0.098	3	3
MAP2K2	-0.014	0.051	0.21	2	-0.14	6	8
T-DHT/AR/PELP1/Src/PI3K	-0.002	0.038	-10000	0	-0.15	5	5
GNAZ	0.01	0.002	-10000	0	-10000	0	0
SHBG	0.01	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.007	0.052	-10000	0	-0.22	3	3
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	-0.002	0.001	0.004	1	-10000	0	1
Gi family/GTP	-0.003	0.028	-10000	0	-0.1	5	5
CDC42	0.01	0	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.014	0.059	-10000	0	-0.16	11	11
epithelial cell differentiation	0.009	0.036	-10000	0	-0.086	10	10
CYFIP2	0.009	0.004	-10000	0	-10000	0	0
ENAH	-0.021	0.021	-10000	0	-0.12	1	1
EGFR	0.01	0.002	-10000	0	-10000	0	0
EPHA2	0.01	0.001	-10000	0	-10000	0	0
MYO6	-0.019	0.028	-10000	0	-0.16	1	1
CTNNB1	0.01	0.001	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.002	0.044	-10000	0	-0.1	12	12
AQP5	-0.046	0.1	-10000	0	-0.34	8	8
CTNND1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.018	0.024	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.016	0.028	-10000	0	-0.16	1	1
EGF	0.007	0.005	-10000	0	-10000	0	0
NCKAP1	0.01	0.001	-10000	0	-10000	0	0
AQP3	-0.037	0.089	-10000	0	-0.34	6	6
cortical microtubule organization	0.009	0.036	-10000	0	-0.086	10	10
GO:0000145	-0.017	0.023	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.011	0.037	-10000	0	-0.086	10	10
MLLT4	0.01	0.002	-10000	0	-10000	0	0
ARF6/GDP	-0.023	0.026	-10000	0	-0.085	11	11
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.019	-10000	0	-0.093	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.013	0.025	-10000	0	-10000	0	0
PVRL2	0.01	0	-10000	0	-10000	0	0
ZYX	-0.018	0.025	-10000	0	-10000	0	0
ARF6/GTP	0.026	0.018	-10000	0	-0.087	2	2
CDH1	0.009	0.003	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.003	0.04	-10000	0	-0.087	14	14
RhoA/GDP	0.009	0.035	-10000	0	-0.083	10	10
actin cytoskeleton organization	-0.019	0.03	-10000	0	-0.096	10	10
IGF-1R heterotetramer	0.01	0	-10000	0	-10000	0	0
GIT1	0.01	0	-10000	0	-10000	0	0
IGF1R	0.01	0	-10000	0	-10000	0	0
IGF1	0.009	0.003	-10000	0	-10000	0	0
DIAPH1	-0.058	0.19	-10000	0	-0.52	12	12
Wnt receptor signaling pathway	-0.009	0.036	0.086	10	-10000	0	10
RHOA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.023	0.026	-10000	0	-0.086	11	11
CTNNA1	0.01	0	-10000	0	-10000	0	0
VCL	-0.02	0.031	-10000	0	-0.098	10	10
EFNA1	0.01	0	-10000	0	-10000	0	0
LPP	-0.019	0.024	-10000	0	-10000	0	0
Ephrin A1/EPHA2	0.006	0.035	-10000	0	-0.082	11	11
SEC6/SEC8	-0.023	0.027	-10000	0	-0.087	11	11
MGAT3	-0.016	0.028	-10000	0	-0.16	1	1
HGF/MET	-0.004	0.045	-10000	0	-0.091	16	16
HGF	0.008	0.004	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.014	0.059	-10000	0	-0.16	11	11
actin cable formation	-0.023	0.043	-10000	0	-0.17	2	2
KIAA1543	-0.015	0.026	-10000	0	-0.15	1	1
KIFC3	-0.018	0.025	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ACTN1	-0.018	0.025	-10000	0	-10000	0	0
NCK1/GIT1	0.014	0.015	-10000	0	-0.12	1	1
mol:GDP	0.009	0.036	-10000	0	-0.086	10	10
EXOC4	0.01	0	-10000	0	-10000	0	0
STX4	-0.018	0.025	-10000	0	-10000	0	0
PIP5K1C	-0.018	0.025	-10000	0	-10000	0	0
LIMA1	0.01	0.002	-10000	0	-10000	0	0
ABI1	0.01	0	-10000	0	-10000	0	0
ROCK1	-0.023	0.024	-10000	0	-0.13	1	1
adherens junction assembly	-0.036	0.059	-10000	0	-0.2	1	1
IGF-1R heterotetramer/IGF1	0.002	0.039	-10000	0	-0.088	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.012	0.022	-10000	0	-0.12	2	2
MET	0.01	0.002	-10000	0	-10000	0	0
PLEKHA7	-0.018	0.025	-10000	0	-10000	0	0
mol:GTP	0.023	0.018	-10000	0	-0.092	2	2
establishment of epithelial cell apical/basal polarity	-0.023	0.026	-10000	0	-0.15	1	1
cortical actin cytoskeleton stabilization	-0.014	0.059	-10000	0	-0.16	11	11
regulation of cell-cell adhesion	-0.019	0.03	-10000	0	-0.096	10	10
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.014	0.059	-10000	0	-0.16	11	11

×

IGF1 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
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.01	0	-10000	0	-10000	0	0
CRKL	-0.002	0.032	0.087	6	-0.11	3	9
GRB2/SOS1/SHC	0.019	0.014	-10000	0	-0.1	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.004	0.023	-10000	0	-0.11	3	3
IGF-1R heterotetramer/IGF1/PTP1B	0.014	0.024	-10000	0	-0.1	3	3
AKT1	-0.007	0.033	0.08	6	-0.099	3	9
BAD	-0.008	0.031	0.075	6	-0.096	3	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.002	0.032	0.087	6	-0.11	3	9
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.006	0.023	-10000	0	-0.11	3	3
RAF1	0.001	0.03	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.016	0.028	-10000	0	-0.1	4	4
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.007	0.025	-10000	0	-0.12	3	3
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
RPS6KB1	-0.007	0.033	0.08	6	-0.099	3	9
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.003	0.028	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.014	0.015	-10000	0	-0.12	1	1
HRAS/GTP	0.007	0.023	-10000	0	-0.094	4	4
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.022	0.026	-10000	0	-0.085	4	4
IGF-1R heterotetramer	0.011	0.012	0.031	7	-0.041	3	10
IGF-1R heterotetramer/IGF1/IRS/Nck	0.013	0.025	-10000	0	-0.11	3	3
Crk/p130 Cas/Paxillin	0.016	0.024	-10000	0	-0.1	3	3
IGF1R	0.011	0.012	0.031	7	-0.041	3	10
IGF1	0.01	0.004	-10000	0	-10000	0	0
IRS2/Crk	0.003	0.022	-10000	0	-0.1	3	3
PI3K	0.015	0.03	-10000	0	-0.097	5	5
apoptosis	0.008	0.03	-10000	0	-10000	0	0
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
PRKCD	0	0.051	-10000	0	-0.2	4	4
RAF1/14-3-3 E	0.007	0.029	-10000	0	-10000	0	0
BAD/14-3-3	-0.009	0.031	-10000	0	-10000	0	0
PRKCZ	-0.007	0.033	0.08	6	-0.099	3	9
Crk/p130 Cas/Paxillin/FAK1	-0.017	0.019	-10000	0	-0.095	3	3
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.002	0.054	-10000	0	-0.21	4	4
BCAR1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.018	0.029	-10000	0	-0.12	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0.001	-10000	0	-10000	0	0
IRS1/NCK2	0.013	0.033	0.094	6	-0.11	3	9
GRB10	0.01	0.001	-10000	0	-10000	0	0
PTPN11	-0.002	0.032	0.087	6	-0.11	3	9
IRS1	0.008	0.035	0.098	6	-0.12	3	9
IRS2	-0.002	0.032	0.087	6	-0.11	3	9
IGF-1R heterotetramer/IGF1	0.008	0.03	-10000	0	-0.14	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	-0.006	0.034	0.084	6	-0.1	3	9
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	-0.001	0.054	-10000	0	-0.22	4	4
SHC1	0.01	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.006	0.043	-10000	0	-0.22	2	2
NT3 (dimer)/TRKC	-0.002	0.038	-10000	0	-0.12	7	7
NT3 (dimer)/TRKB	-0.011	0.047	-10000	0	-0.11	14	14
SHC/Grb2/SOS1/GAB1/PI3K	0.004	0.029	-10000	0	-0.14	3	3
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	0.008	0.004	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	0.008	0.004	-10000	0	-10000	0	0
NTRK2	0.007	0.005	-10000	0	-10000	0	0
NTRK3	0.009	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	-0.007	0.047	-10000	0	-0.11	13	13
neuron apoptosis	0.01	0.092	0.28	3	-10000	0	3
SHC 2-3/Grb2	-0.011	0.098	-10000	0	-0.3	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.032	0.081	-10000	0	-0.32	3	3
SHC3	-0.033	0.081	-10000	0	-0.38	2	2
STAT3 (dimer)	0.014	0	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.009	0.049	-10000	0	-0.12	13	13
RIN/GDP	0.014	0.06	0.15	6	-0.17	1	7
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0.001	-10000	0	-10000	0	0
DNAJA3	-0.031	0.077	-10000	0	-0.19	13	13
RIN/GTP	0.001	0.002	-10000	0	-10000	0	0
CCND1	0.008	0	-10000	0	-10000	0	0
MAGED1	0.01	0	-10000	0	-10000	0	0
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.007	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.019	0.014	-10000	0	-0.1	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.023	0.064	-10000	0	-0.12	21	21
TRKA/NEDD4-2	0.007	0.03	-10000	0	-0.12	4	4
ELMO1	0.01	0.002	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.011	0.018	-10000	0	-0.1	2	2
NGF	0.008	0.004	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.01	0	-10000	0	-10000	0	0
RIT2	0.001	0.003	-10000	0	-10000	0	0
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.01	0	-10000	0	-10000	0	0
DNM1	0.009	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.025	0.078	-10000	0	-0.19	13	13
mol:GDP	0.021	0.086	0.21	7	-0.21	2	9
NGF (dimer)	0.008	0.004	-10000	0	-10000	0	0
RhoG/GDP	0.004	0.02	-10000	0	-0.12	2	2
RIT1/GDP	0.019	0.066	0.16	7	-0.17	1	8
TIAM1	0.009	0.003	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.004	0.046	-10000	0	-0.11	12	12
KIDINS220/CRKL/C3G	0.015	0	-10000	0	-10000	0	0
SHC/RasGAP	0.014	0.015	-10000	0	-0.12	1	1
FRS2 family/SHP2	0.021	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.025	0.013	-10000	0	-0.093	1	1
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	0.005	0.005	-10000	0	-10000	0	0
RAP1/GDP	-0.006	0.033	-10000	0	-0.13	2	2
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	0.008	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.005	0.036	-10000	0	-0.1	8	8
Schwann cell development	-0.01	0.015	-10000	0	-0.041	11	11
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.025	0.013	-10000	0	-0.093	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.009	0	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.005	0.033	-10000	0	-0.081	12	12
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.014	0.015	-10000	0	-0.12	1	1
Rap1/GTP	0	0.024	-10000	0	-10000	0	0
STAT3	0.014	0	-10000	0	-10000	0	0
axon guidance	-0.007	0.031	-10000	0	-0.079	12	12
MAPK3	-0.001	0.092	0.14	18	-0.11	21	39
MAPK1	-0.001	0.092	0.14	18	-0.11	21	39
CDC42/GDP	0.019	0.066	0.16	7	-0.17	1	8
NTF3	0.005	0.005	-10000	0	-10000	0	0
NTF4	0.007	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.006	0.036	-10000	0	-0.1	8	8
PI3K	0.012	0.022	-10000	0	-0.12	2	2
FRS3	0.01	0	-10000	0	-10000	0	0
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.01	0	-10000	0	-10000	0	0
RASGRF1	-0.033	0.088	-10000	0	-0.22	12	12
SOS1	0.01	0.001	-10000	0	-10000	0	0
MCF2L	0.005	0.059	0.14	10	-0.1	7	17
RGS19	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.005	0.074	-10000	0	-0.31	2	2
Rac1/GDP	0.019	0.066	0.16	7	-0.17	1	8
NGF (dimer)/TRKA/GRIT	0	0.034	-10000	0	-0.1	8	8
neuron projection morphogenesis	-0.009	0.097	-10000	0	-0.32	3	3
NGF (dimer)/TRKA/NEDD4-2	0.006	0.036	-10000	0	-0.1	8	8
MAP2K1	-0.01	0.009	-10000	0	-0.088	1	1
NGFR	0.008	0.004	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GIPC/GAIP	-0.012	0.052	-10000	0	-0.14	11	11
RAS family/GTP/PI3K	0.003	0.029	-10000	0	-0.14	3	3
FRS2 family/SHP2/GRB2/SOS1	0.029	0.013	-10000	0	-0.088	1	1
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0.014	0.015	-10000	0	-0.12	1	1
PRKCI	0.01	0.001	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.002	-10000	0	-10000	0	0
MAPKKK cascade	-0.031	0.15	-10000	0	-0.46	8	8
RASA1	0.01	0.001	-10000	0	-10000	0	0
TRKA/c-Abl	0.007	0.03	-10000	0	-0.12	4	4
SQSTM1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.001	0.044	-10000	0	-0.1	12	12
NGF (dimer)/TRKA/p62/Atypical PKCs	0.011	0.04	-10000	0	-0.088	11	11
MATK	0.006	0.005	-10000	0	-10000	0	0
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.011	0.027	-10000	0	-0.11	4	4
NGF (dimer)/TRKA	-0.028	0.081	-10000	0	-0.2	13	13
Rac1/GTP	-0.032	0.065	-10000	0	-0.15	15	15
FRS2 family/SHP2/CRK family	0.031	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.009	0.035	-10000	0	-0.14	2	2
adherens junction organization	-0.019	0.058	-10000	0	-0.17	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.001	0.038	0.12	2	-10000	0	2
FMN1	-0.017	0.057	-10000	0	-0.17	9	9
mol:IP3	-0.007	0.032	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.057	-10000	0	-0.17	9	9
CTNNB1	0.011	0.002	-10000	0	-10000	0	0
AKT1	-0.009	0.038	-10000	0	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.021	0.088	-10000	0	-0.25	10	10
CTNND1	0.01	0.003	-10000	0	-0.009	2	2
mol:PI-4-5-P2	-0.017	0.054	-10000	0	-0.16	9	9
VASP	-0.017	0.054	-10000	0	-0.17	9	9
ZYX	-0.017	0.054	-10000	0	-0.17	9	9
JUB	-0.017	0.054	-10000	0	-0.17	9	9
EGFR(dimer)	-0.008	0.055	-10000	0	-0.17	8	8
E-cadherin/beta catenin-gamma catenin	0.009	0.034	-10000	0	-0.088	9	9
mol:PI-3-4-5-P3	-0.001	0.042	-10000	0	-0.11	9	9
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PI3K	-0.001	0.043	-10000	0	-0.11	9	9
FYN	-0.002	0.033	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.031	-10000	0	-10000	0	0
JUP	0.011	0.002	-10000	0	-10000	0	0
PIK3R1	0.01	0.003	-10000	0	-0.011	2	2
mol:DAG	-0.007	0.032	-10000	0	-10000	0	0
CDH1	0.009	0.003	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.038	0.12	2	-10000	0	2
establishment of polarity of embryonic epithelium	-0.017	0.054	-10000	0	-0.16	9	9
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
EGFR	0.01	0.002	-10000	0	-10000	0	0
CASR	-0.01	0.027	-10000	0	-10000	0	0
RhoA/GTP	-0.002	0.032	-10000	0	-10000	0	0
AKT2	-0.009	0.038	-10000	0	-0.11	9	9
actin cable formation	-0.021	0.057	-10000	0	-0.17	10	10
apoptosis	0.01	0.037	-10000	0	-10000	0	0
CTNNA1	0.01	0.003	-10000	0	-0.009	2	2
mol:GDP	-0.009	0.03	-10000	0	-10000	0	0
PIP5K1A	-0.017	0.054	-10000	0	-0.17	9	9
PLCG1	-0.007	0.032	-10000	0	-10000	0	0
Rac1/GTP	-0.005	0.054	-10000	0	-0.16	8	8
homophilic cell adhesion	-0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.007	0.039	-9999	-0.1	9	9
E-cadherin/beta catenin	-0.002	0.046	-9999	-0.12	10	10
CTNNB1	0.01	0.001	-9999	-10000	0	0
JUP	0.01	0.001	-9999	-10000	0	0
CDH1	0.009	0.003	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.004	0.037	-10000	0	-0.084	14	14
RGS9BP	0.009	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.003	0.005	-10000	0	-10000	0	0
mol:Na +	0.004	0.005	-10000	0	-10000	0	0
mol:ADP	-0.002	0.002	-10000	0	-10000	0	0
GNAT2	0.008	0.004	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.013	0.027	-10000	0	-0.1	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.003	0.021	-10000	0	-0.1	3	3
GRK7	0.004	0.005	-10000	0	-10000	0	0
CNGB3	0.005	0.005	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.003	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.026	0.14	3	-10000	0	3
Cone PDE6	0.008	0.033	-10000	0	-0.098	6	6
Cone Metarhodopsin II	0.004	0.005	-10000	0	-10000	0	0
Na + (4 Units)	0.005	0.006	-10000	0	-10000	0	0
GNAT2/GDP	0.016	0.024	-10000	0	-0.085	4	4
GNB5	0.01	0.002	-10000	0	-10000	0	0
mol:GMP (4 units)	0.009	0.051	0.16	7	-0.088	3	10
Cone Transducin	-0.004	0.04	-10000	0	-0.09	14	14
SLC24A2	0.002	0.004	-10000	0	-10000	0	0
GNB3/GNGT2	-0.012	0.052	-10000	0	-0.12	14	14
GNB3	0.007	0.005	-10000	0	-10000	0	0
GNAT2/GTP	0.006	0.003	-10000	0	-10000	0	0
CNGA3	0.002	0.004	-10000	0	-10000	0	0
ARR3	0.004	0.005	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.005	0.005	-10000	0	-10000	0	0
mol:Pi	0.013	0.027	-10000	0	-0.1	4	4
Cone CNG Channel	0.005	0.018	-10000	0	-0.079	3	3
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.002	0.004	-10000	0	-10000	0	0
RGS9	0.009	0.003	-10000	0	-10000	0	0
PDE6C	0.002	0.004	-10000	0	-10000	0	0
GNGT2	0.009	0.003	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.003	0.005	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.01	0.026	-10000	0	-0.12	3	3
CRKL	-0.006	0.055	-10000	0	-0.24	1	1
mol:PIP3	0.003	0.005	-10000	0	-10000	0	0
AKT1	-0.001	0.004	-10000	0	-10000	0	0
PTK2B	0.01	0	-10000	0	-10000	0	0
RAPGEF1	-0.007	0.053	-10000	0	-0.23	1	1
RANBP10	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.006	0.039	-10000	0	-0.1	9	9
MAP3K5	-0.007	0.077	-10000	0	-0.23	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	0.011	0.038	-10000	0	-0.093	9	9
AP1	-0.001	0.035	-10000	0	-0.13	5	5
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.047	0.2	-10000	0	-0.74	6	6
STAT3 (dimer)	-0.008	0.065	-10000	0	-0.17	9	9
GAB1/CRKL/SHP2/PI3K	0.006	0.057	-10000	0	-0.22	1	1
INPP5D	0.009	0.003	-10000	0	-10000	0	0
CBL/CRK	0	0.055	-10000	0	-0.23	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0
ELK1	-0.009	0.011	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.006	0.034	-10000	0	-0.11	3	3
PAK1	-0.003	0.004	-10000	0	-10000	0	0
HGF/MET/RANBP10	0.006	0.039	-10000	0	-0.1	9	9
HRAS	-0.014	0.1	-10000	0	-0.46	3	3
DOCK1	-0.007	0.053	-10000	0	-0.23	1	1
GAB1	-0.005	0.058	-10000	0	-0.25	1	1
CRK	-0.006	0.055	-10000	0	-0.24	1	1
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.026	0.12	-10000	0	-0.37	9	9
JUN	0.01	0.002	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.006	0.047	0.078	5	-0.13	9	14
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell morphogenesis	-0.017	0.069	-10000	0	-0.2	9	9
GRB2/SHC	0.006	0.045	-10000	0	-0.11	9	9
FOS	0.009	0.003	-10000	0	-10000	0	0
GLMN	0.001	0	-10000	0	-10000	0	0
cell motility	-0.009	0.011	-10000	0	-10000	0	0
HGF/MET/MUC20	0	0.036	-10000	0	-0.1	9	9
cell migration	0.006	0.045	-10000	0	-0.11	9	9
GRB2	0.01	0	-10000	0	-10000	0	0
CBL	0.01	0	-10000	0	-10000	0	0
MET/RANBP10	0.01	0.026	-10000	0	-0.12	3	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.01	0.056	-10000	0	-0.16	9	9
MET/MUC20	0.003	0.025	-10000	0	-0.12	3	3
RAP1B	-0.009	0.05	-10000	0	-0.22	1	1
RAP1A	-0.009	0.05	-10000	0	-0.22	1	1
HGF/MET/RANBP9	0.006	0.039	-10000	0	-0.1	9	9
RAF1	-0.015	0.098	-10000	0	-0.44	3	3
STAT3	-0.008	0.066	-10000	0	-0.17	9	9
cell proliferation	-0.02	0.086	-10000	0	-0.25	9	9
RPS6KB1	-0.003	0.022	-10000	0	-10000	0	0
MAPK3	-0.011	0.01	-10000	0	-10000	0	0
MAPK1	-0.011	0.01	-10000	0	-10000	0	0
RANBP9	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.025	0.11	-10000	0	-0.38	5	5
SRC	-0.007	0.057	-10000	0	-0.15	9	9
PI3K	0.004	0.047	-10000	0	-0.11	9	9
MET/Glomulin	0.002	0.03	-10000	0	-0.13	4	4
SOS1	0.01	0.001	-10000	0	-10000	0	0
MAP2K1	-0.015	0.092	-10000	0	-0.42	3	3
MET	0.01	0.002	-10000	0	-10000	0	0
MAP4K1	-0.006	0.075	-10000	0	-0.24	4	4
PTK2	0.01	0	-10000	0	-10000	0	0
MAP2K2	-0.015	0.092	-10000	0	-0.42	3	3
BAD	-0.003	0.004	-10000	0	-10000	0	0
MAP2K4	-0.013	0.074	-10000	0	-0.21	5	5
SHP2/GRB2/SOS1/GAB1	-0.001	0.057	-10000	0	-0.22	3	3
INPPL1	0.01	0	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
SH3KBP1	0.01	0	-10000	0	-10000	0	0
HGS	-0.008	0.043	0.072	5	-0.12	9	14
PLCgamma1/PKC	0.008	0	-10000	0	-10000	0	0
HGF	0.008	0.004	-10000	0	-10000	0	0
RASA1	0.01	0.001	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
PTPRJ	0.01	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.004	0.051	-10000	0	-0.13	9	9
PDPK1	0	0.005	-10000	0	-10000	0	0
HGF/MET/SHIP	0.003	0.047	-10000	0	-0.12	9	9

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.01	0.004	-10000	0	-0.008	3	3
HDAC2	0.009	0.004	-10000	0	-0.009	3	3
GNB1/GNG2	0.018	0.02	-10000	0	-0.1	2	2
forebrain development	-0.002	0.11	0.29	3	-0.3	7	10
GNAO1	0.01	0.004	0.024	3	-10000	0	3
SMO/beta Arrestin2	0.018	0.01	0.074	1	-10000	0	1
SMO	0.011	0.005	0.038	3	-10000	0	3
ARRB2	0.011	0.003	0.028	3	-10000	0	3
GLI3/SPOP	-0.006	0.072	-10000	0	-0.24	6	6
mol:GTP	0.001	0.002	0.013	3	-10000	0	3
GSK3B	0.01	0	-10000	0	-10000	0	0
GNAI2	0.011	0.003	0.024	3	-10000	0	3
SIN3/HDAC complex	0.02	0.024	-10000	0	-0.093	3	3
GNAI1	0.011	0.003	0.023	3	-10000	0	3
XPO1	0.012	0.01	0.061	3	-10000	0	3
GLI1/Su(fu)	0.005	0.082	0.28	3	-10000	0	3
SAP30	0.009	0.004	-10000	0	-0.009	3	3
mol:GDP	0.011	0.005	0.038	3	-10000	0	3
MIM/GLI2A	0.016	0.038	0.25	2	-10000	0	2
IFT88	0.01	0.002	-10000	0	-10000	0	0
GNAI3	0.011	0.002	0.023	3	-10000	0	3
GLI2	-0.014	0.053	-10000	0	-0.25	1	1
GLI3	-0.012	0.073	-10000	0	-0.25	6	6
CSNK1D	0.01	0	-10000	0	-10000	0	0
CSNK1E	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.004	-10000	0	-0.008	3	3
embryonic digit morphogenesis	0.01	0.002	-10000	0	-10000	0	0
GNG2	0.01	0.002	-10000	0	-10000	0	0
Gi family/GTP	0.002	0.043	-10000	0	-0.14	6	6
SIN3B	0.009	0.004	-10000	0	-0.009	3	3
SIN3A	0.01	0.004	-10000	0	-0.008	3	3
GLI3/Su(fu)	-0.004	0.058	-10000	0	-0.29	2	2
GLI2/Su(fu)	-0.006	0.048	-10000	0	-0.22	1	1
FOXA2	-0.013	0.15	0.5	2	-0.54	4	6
neural tube patterning	-0.002	0.11	0.29	3	-0.3	7	10
SPOP	0.01	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.015	0.006	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
CSNK1G2	0.01	0	-10000	0	-10000	0	0
CSNK1G3	0.01	0.001	-10000	0	-10000	0	0
MTSS1	0.016	0.038	0.25	2	-10000	0	2
embryonic limb morphogenesis	-0.002	0.11	0.29	3	-0.3	7	10
SUFU	0.009	0.007	-10000	0	-10000	0	0
LGALS3	0.009	0.004	-10000	0	-10000	0	0
catabolic process	-0.014	0.085	-10000	0	-0.32	4	4
GLI3A/CBP	-0.005	0.07	-10000	0	-0.25	6	6
KIF3A	0.01	0.002	-10000	0	-10000	0	0
GLI1	-0.002	0.12	0.29	3	-0.3	7	10
RAB23	0.01	0.002	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
IFT172	0.01	0	-10000	0	-10000	0	0
RBBP7	0.009	0.004	-10000	0	-0.009	3	3
Su(fu)/Galectin3	0.012	0.006	-10000	0	-10000	0	0
GNAZ	0.01	0.003	0.023	3	-10000	0	3
RBBP4	0.01	0.004	-10000	0	-0.008	3	3
CSNK1G1	0.01	0	-10000	0	-10000	0	0
PIAS1	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GLI2/SPOP	-0.008	0.052	-10000	0	-0.24	1	1
STK36	0.012	0.009	0.059	3	-10000	0	3
Gi family/GNB1/GNG2/GDP	0.002	0.044	-10000	0	-0.13	7	7
PTCH1	0	0.11	-10000	0	-10000	0	0
MIM/GLI1	0	0.12	0.42	2	-0.3	5	7
CREBBP	-0.005	0.069	-10000	0	-0.25	6	6
Su(fu)/SIN3/HDAC complex	0.009	0.006	-10000	0	-10000	0	0

×

Aurora A signaling

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
Aurora A/GADD45A	0.015	0.029	0.087	2	-0.16	1	3
BIRC5	0.01	0.002	-10000	0	-10000	0	0
NFKBIA	0.005	0.025	0.084	7	-10000	0	7
CPEB1	0.009	0.003	-10000	0	-10000	0	0
AKT1	0.005	0.025	0.084	7	-10000	0	7
NDEL1	0.01	0	-10000	0	-10000	0	0
Aurora A/BRCA1	0.013	0.025	0.077	2	-0.14	1	3
NDEL1/TACC3	0.019	0.025	0.08	2	-0.14	1	3
GADD45A	0.01	0	-10000	0	-10000	0	0
GSK3B	0.013	0.014	0.057	7	-0.012	2	9
PAK1/Aurora A	0.015	0.029	0.087	2	-0.16	1	3
MDM2	0.01	0	-10000	0	-10000	0	0
JUB	0.01	0	-10000	0	-10000	0	0
TPX2	-0.005	0.001	-10000	0	-10000	0	0
TP53	0.012	0.018	-10000	0	-10000	0	0
DLG7	0.009	0.024	0.086	7	-10000	0	7
AURKAIP1	0.01	0	-10000	0	-10000	0	0
ARHGEF7	0.01	0	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.02	0.026	-10000	0	-0.14	1	1
G2/M transition of mitotic cell cycle	0.013	0.025	0.076	2	-0.14	1	3
AURKA	0.014	0.031	0.11	7	-10000	0	7
AURKB	-0.024	0.093	-10000	0	-0.28	8	8
CDC25B	0	0.049	0.087	2	-0.19	4	6
G2/M transition checkpoint	0.013	0.025	0.076	2	-0.14	1	3
mRNA polyadenylation	0.006	0.032	0.076	1	-0.098	5	6
Aurora A/CPEB	0.007	0.032	0.077	1	-0.098	5	6
Aurora A/TACC1/TRAP/chTOG	0.022	0.03	-10000	0	-0.14	1	1
BRCA1	0.01	0	-10000	0	-10000	0	0
centrosome duplication	0.015	0.028	0.086	2	-0.16	1	3
regulation of centrosome cycle	0.018	0.024	-10000	0	-0.13	1	1
spindle assembly	0.021	0.03	-10000	0	-0.14	1	1
TDRD7	0.01	0.002	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.016	0.028	-10000	0	-0.098	3	3
CENPA	-0.023	0.096	-10000	0	-0.33	7	7
Aurora A/PP2A	0.015	0.029	0.087	2	-0.16	1	3
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.007	0.029	-10000	0	-0.18	1	1
negative regulation of DNA binding	0.012	0.018	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.015	0	-10000	0	-10000	0	0
RASA1	0.01	0.001	-10000	0	-10000	0	0
Ajuba/Aurora A	0.013	0.025	0.077	2	-0.14	1	3
mitotic prometaphase	0.004	0.018	0.068	6	-10000	0	6
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.031	0.11	7	-10000	0	7
TACC1	0.01	0	-10000	0	-10000	0	0
TACC3	0.01	0	-10000	0	-10000	0	0
Aurora A/Antizyme1	0.02	0.026	-10000	0	-0.14	1	1
Aurora A/RasGAP	0.014	0.027	0.087	1	-0.16	1	2
OAZ1	0.01	0	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.013	0.014	0.057	7	-0.012	2	9
GIT1	0.01	0	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.021	0	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.005	0.001	-10000	0	-10000	0	0
PPP2R5D	0.01	0	-10000	0	-10000	0	0
Aurora A/TPX2	0.008	0.025	0.081	2	-0.14	1	3
PAK1	0.01	0	-10000	0	-10000	0	0
CKAP5	0.01	0	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.004	0.041	-10000	0	-0.1	10	10
fibroblast growth factor receptor signaling pathway	0.004	0.04	-10000	0	-0.1	10	10
LAMA1	0.008	0.004	-10000	0	-10000	0	0
PRNP	0.01	0	-10000	0	-10000	0	0
GPC1/SLIT2	0.003	0.039	-10000	0	-0.12	7	7
SMAD2	-0.01	0.013	-10000	0	-0.093	2	2
GPC1/PrPc/Cu2+	0.013	0.013	-10000	0	-0.1	1	1
GPC1/Laminin alpha1	-0.003	0.046	-10000	0	-0.12	10	10
TDGF1	0.002	0.004	-10000	0	-10000	0	0
CRIPTO/GPC1	0.007	0.015	-10000	0	-0.12	1	1
APP/GPC1	0.014	0.015	-10000	0	-0.12	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.004	0.02	0.14	1	-0.1	1	2
FLT1	0.01	0.002	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.018	0.019	-10000	0	-0.1	2	2
SERPINC1	0.006	0.005	-10000	0	-10000	0	0
FYN	-0.004	0.02	0.14	1	-0.1	1	2
FGR	-0.002	0.017	0.14	1	-10000	0	1
positive regulation of MAPKKK cascade	0.004	0.088	0.17	9	-0.17	4	13
SLIT2	0.009	0.003	-10000	0	-10000	0	0
GPC1/NRG	0.012	0.016	-10000	0	-0.12	1	1
NRG1	0.008	0.004	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.015	0.024	-10000	0	-0.1	3	3
LYN	-0.004	0.02	0.14	1	-0.1	1	2
mol:Spermine	-0.003	0	-10000	0	-10000	0	0
cell growth	0.004	0.04	-10000	0	-0.1	10	10
BMP signaling pathway	-0.01	0.001	-10000	0	-10000	0	0
SRC	-0.004	0.02	0.14	1	-0.1	1	2
TGFBR1	0.01	0.001	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.005	0.005	-10000	0	-10000	0	0
GPC1	0.01	0.001	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.01	0.001	-10000	0	-10000	0	0
VEGFA	0.01	0.002	-10000	0	-10000	0	0
BLK	-0.003	0.02	0.14	1	-0.1	1	2
HCK	-0.004	0.02	0.14	1	-0.1	1	2
FGF2	0.009	0.004	-10000	0	-10000	0	0
FGFR1	0.01	0.002	-10000	0	-10000	0	0
VEGFR1 homodimer	0.01	0.002	-10000	0	-10000	0	0
TGFBR2	0.01	0	-10000	0	-10000	0	0
cell death	0.013	0.015	-10000	0	-0.12	1	1
ATIII/GPC1	0.01	0.015	-10000	0	-0.12	1	1
PLA2G2A/GPC1	-0.008	0.047	-10000	0	-0.12	11	11
LCK	-0.002	0.02	0.14	1	-0.1	1	2
neuron differentiation	0.012	0.016	-10000	0	-0.12	1	1
PrPc/Cu2+	0.008	0	-10000	0	-10000	0	0
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.01	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.001	0.075	0.15	4	-0.2	8	12
BAG4	0.01	0.002	-10000	0	-10000	0	0
BAD	-0.001	0.027	-10000	0	-10000	0	0
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.007	0.005	-10000	0	-10000	0	0
BAX	-0.001	0.027	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.001	0.021	0.053	4	-0.048	8	12
IKBKB	-0.003	0.072	-10000	0	-0.19	8	8
MAP2K2	-0.002	0.024	-10000	0	-10000	0	0
MAP2K1	-0.002	0.024	-10000	0	-10000	0	0
SMPD1	0.001	0.021	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0	0.073	-10000	0	-0.19	8	8
MAP2K4	-0.002	0.026	-10000	0	-10000	0	0
protein ubiquitination	-0.003	0.072	-10000	0	-0.19	8	8
EnzymeConsortium:2.7.1.37	-0.003	0.024	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-0.001	1	1
RAF1	-0.001	0.026	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
mol:ceramide	0.001	0.029	0.071	4	-0.066	8	12
I-kappa-B-alpha/RELA/p50/ubiquitin	0.014	0	-10000	0	-10000	0	0
MADD	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.027	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
RELA/p50	0.01	0	-10000	0	-10000	0	0
MAPK3	-0.001	0.024	-10000	0	-10000	0	0
MAPK1	-0.001	0.024	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.015	0	-10000	0	-10000	0	0
FADD	-0.001	0.075	0.15	4	-0.2	8	12
KSR1	0	0.027	-10000	0	-10000	0	0
MAPK8	-0.004	0.027	-10000	0	-0.12	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.003	0.072	-10000	0	-0.19	8	8
TNF R/SODD	0.012	0.022	-10000	0	-0.12	2	2
TNF	0.006	0.005	-10000	0	-10000	0	0
CYCS	-0.003	0.028	-10000	0	-10000	0	0
IKBKG	-0.003	0.072	-10000	0	-0.19	8	8
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.006	0.069	-10000	0	-0.2	8	8
RELA	0.01	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AIFM1	-0.002	0.027	-10000	0	-10000	0	0
TNF/TNF R/SODD	0.013	0.023	-10000	0	-0.1	3	3
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.009	0.019	-10000	0	-10000	0	0
NSMAF	-0.001	0.074	0.15	4	-0.19	8	12
response to hydrogen peroxide	0	0	-10000	0	-0.001	1	1
BCL2	0.01	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.01	0	-10000	0	-10000	0	0
Rac1/GDP	0.01	0.006	0.025	6	-10000	0	6
DOCK1	0.01	0	-10000	0	-10000	0	0
ITGA4	0.007	0.005	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.043	-10000	0	-0.12	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.008	0.032	-10000	0	-0.1	6	6
alpha4/beta7 Integrin/Paxillin	0.001	0.034	-10000	0	-0.093	9	9
lamellipodium assembly	0.003	0.043	-10000	0	-0.26	2	2
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PI3K	0.012	0.022	-10000	0	-0.12	2	2
ARF6	0.01	0	-10000	0	-10000	0	0
TLN1	0.01	0	-10000	0	-10000	0	0
PXN	-0.006	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
ARF6/GTP	0.01	0.027	-10000	0	-0.082	6	6
cell adhesion	0.009	0.029	-10000	0	-0.087	6	6
CRKL/CBL	0.015	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.005	0.029	-10000	0	-0.093	6	6
ITGB1	0.01	0	-10000	0	-10000	0	0
ITGB7	0.01	0.002	-10000	0	-10000	0	0
ARF6/GDP	0.01	0.006	0.025	6	-10000	0	6
alpha4/beta1 Integrin/Paxillin/VCAM1	0.003	0.041	-10000	0	-0.1	9	9
p130Cas/Crk/Dock1	0.021	0	-10000	0	-10000	0	0
VCAM1	0.008	0.004	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin	0.01	0.029	-10000	0	-0.088	6	6
alpha4/beta1 Integrin/Paxillin/GIT1	0.01	0.029	-10000	0	-0.088	6	6
BCAR1	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.029	0.087	6	-10000	0	6
CBL	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GIT1	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.01	0.029	-10000	0	-0.088	6	6
Rac1/GTP	0.003	0.047	-10000	0	-0.29	2	2

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.019	0.057	-9999	-0.14	14	14
FZD6	0.009	0.003	-9999	-10000	0	0
WNT6	0.008	0.004	-9999	-10000	0	0
WNT4	0.01	0.002	-9999	-10000	0	0
FZD3	0.01	0	-9999	-10000	0	0
WNT5A	0.009	0.004	-9999	-10000	0	0
WNT11	0.01	0.002	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.18	-10000	0	-10000	0	0
CRP	0.028	0.18	-10000	0	-10000	0	0
cell cycle arrest	0.028	0.2	-10000	0	-0.51	2	2
TIMP1	0.03	0.16	-10000	0	-10000	0	0
IL6ST	0.013	0.017	0.064	2	-10000	0	2
Rac1/GDP	0.014	0.12	0.32	4	-0.24	3	7
AP1	0.023	0.073	-10000	0	-0.43	1	1
GAB2	0.011	0.004	0.032	3	-10000	0	3
TNFSF11	0.028	0.18	-10000	0	-10000	0	0
HSP90B1	0.023	0.053	-10000	0	-10000	0	0
GAB1	0.011	0.003	-10000	0	-10000	0	0
MAPK14	0.013	0.095	0.47	2	-0.24	1	3
AKT1	0.01	0.038	-10000	0	-10000	0	0
FOXO1	0.007	0.036	-10000	0	-10000	0	0
MAP2K6	0.015	0.096	0.41	2	-0.25	1	3
mol:GTP	0.001	0.003	-10000	0	-10000	0	0
MAP2K4	0.028	0.15	0.36	6	-0.3	2	8
MITF	0.01	0.099	0.29	2	-0.23	3	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	-0.04	0.21	-10000	0	-1.1	3	3
CEBPB	0.012	0	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.015	0.069	-10000	0	-0.4	1	1
STAT3	0.013	0.19	-10000	0	-0.53	2	2
STAT1	0.023	0.048	-10000	0	-10000	0	0
CEBPD	0.01	0.24	-10000	0	-0.86	3	3
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PI3K	0.012	0.022	-10000	0	-0.12	2	2
JUN	0.01	0.002	-10000	0	-10000	0	0
PIAS3/MITF	0.014	0.094	0.26	2	-0.22	3	5
MAPK11	0.013	0.095	0.47	2	-0.24	1	3
STAT3 (dimer)/FOXO1	0.008	0.16	-10000	0	-10000	0	0
GRB2/SOS1/GAB family	0.012	0.078	0.15	1	-0.17	5	6
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.001	0.089	0.21	4	-0.21	4	8
GRB2	0.011	0.003	-10000	0	-10000	0	0
JAK2	0.01	0.002	-10000	0	-10000	0	0
LBP	0.031	0.16	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.012	0.014	0.068	2	-10000	0	2
MYC	0.029	0.18	-10000	0	-10000	0	0
FGG	0.03	0.18	0.52	1	-10000	0	1
macrophage differentiation	0.028	0.2	-10000	0	-0.51	2	2
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.012	0.064	0.16	1	-0.16	4	5
JUNB	0.028	0.18	-10000	0	-10000	0	0
FOS	0.009	0.003	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.008	0.1	0.31	2	-0.24	3	5
STAT1/PIAS1	0.021	0.1	-10000	0	-0.25	2	2
GRB2/SOS1/GAB family/SHP2/PI3K	0.013	0.038	-10000	0	-0.21	2	2
STAT3 (dimer)	0.014	0.19	-10000	0	-0.53	2	2
PRKCD	0.029	0.17	0.44	4	-0.37	2	6
IL6R	0.011	0.014	0.068	2	-10000	0	2
SOCS3	0.001	0.11	0.55	2	-10000	0	2
gp130 (dimer)/JAK1/JAK1/LMO4	0.018	0.057	0.16	2	-0.11	8	10
Rac1/GTP	0.012	0.12	0.34	3	-0.27	2	5
HCK	0.01	0.003	-10000	0	-10000	0	0
MAPKKK cascade	0.022	0.073	-10000	0	-0.48	1	1
bone resorption	0.029	0.18	-10000	0	-10000	0	0
IRF1	0.02	0.28	0.54	3	-0.87	4	7
mol:GDP	0.017	0.11	0.31	5	-0.24	3	8
SOS1	0.011	0.004	0.032	3	-10000	0	3
VAV1	0.015	0.12	0.31	5	-0.24	3	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.001	0.1	0.44	2	-0.3	4	6
PTPN11	0.015	0.024	-10000	0	-10000	0	0
IL6/IL6RA	0.011	0.037	0.11	1	-0.12	4	5
gp130 (dimer)/TYK2/TYK2/LMO4	0.013	0.048	0.098	1	-0.1	9	10
gp130 (dimer)/JAK2/JAK2/LMO4	0.01	0.056	-10000	0	-0.12	9	9
IL6	0.011	0.016	0.064	1	-10000	0	1
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.002	0.022	-10000	0	-0.063	2	2
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0.005	-10000	0	-0.009	5	5
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.003	0.078	0.19	2	-0.16	11	13
LMO4	0.015	0.017	0.064	2	-10000	0	2
STAT3 (dimer)/PIAS3	0.017	0.18	-10000	0	-0.51	2	2
MCL1	0.01	0.035	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.002	0.04	-10000	0	-0.084	15	15
MAPK9	0.002	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0	0.001	-10000	0	-10000	0	0
GNB1/GNG2	0.011	0.018	-10000	0	-0.1	2	2
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.002	0	-10000	0	-10000	0	0
Gs family/GTP	-0.009	0.035	-10000	0	-0.087	13	13
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	0.005	0.01	0.027	13	-10000	0	13
GNAL	0.008	0.004	-10000	0	-10000	0	0
GNG2	0.01	0.002	-10000	0	-10000	0	0
CRH	0.001	0.003	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0	-10000	0	-10000	0	0
MAPK11	0.002	0	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.009	0.003	-10000	0	-10000	0	0
CDC42/GTP	-0.002	0.042	-10000	0	-0.12	8	8
PLCG1	-0.009	0.041	-10000	0	-0.13	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
G12/G13	0.015	0	-10000	0	-10000	0	0
cell migration	-0.002	0.042	-10000	0	-0.12	8	8
S1PR5	0.009	0.003	-10000	0	-10000	0	0
S1PR4	0.009	0.004	-10000	0	-10000	0	0
MAPK3	-0.009	0.041	-10000	0	-0.13	8	8
MAPK1	-0.009	0.041	-10000	0	-0.13	8	8
S1P/S1P5/Gi	-0.003	0.039	-10000	0	-0.14	6	6
GNAI1	0.01	0.002	-10000	0	-10000	0	0
CDC42/GDP	0.008	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.012	0.013	-10000	0	-0.1	1	1
RHOA	-0.001	0.041	0.13	6	-0.086	4	10
S1P/S1P4/Gi	-0.006	0.045	-10000	0	-0.14	8	8
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.01	0.002	-10000	0	-10000	0	0
S1P/S1P4/G12/G13	0.013	0.024	-10000	0	-0.091	4	4
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0

×

p38 MAPK signaling 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
TRAF6/ASK1	-0.003	0.029	-10000	0	-0.08	10	10
TRAF2/ASK1	-0.001	0.038	-10000	0	-0.1	10	10
ATM	0.01	0.002	-10000	0	-10000	0	0
MAP2K3	-0.02	0.077	-10000	0	-0.26	5	5
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.03	0.09	-10000	0	-0.2	15	15
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.008	0.004	-10000	0	-10000	0	0
TXN	0.002	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.01	0	-10000	0	-10000	0	0
GADD45B	0.01	0.001	-10000	0	-10000	0	0
MAP3K1	0.01	0	-10000	0	-10000	0	0
MAP3K6	0.01	0.001	-10000	0	-10000	0	0
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
MAP3K4	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.004	0.048	-10000	0	-0.12	11	11
TAK1/TAB family	0	0.012	0.1	1	-10000	0	1
RAC1/OSM/MEKK3	0.02	0	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.011	0.066	-10000	0	-0.22	5	5
TRAF6	0.002	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.009	0.003	-10000	0	-10000	0	0
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.011	0.013	-10000	0	-0.1	1	1
MAPK11	0.01	0.001	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.002	0.038	-10000	0	-0.091	11	11
OSM/MEKK3	0.015	0	-10000	0	-10000	0	0
TAOK1	0.004	0.001	-10000	0	0	7	7
TAOK2	0.004	0.001	-10000	0	0	4	4
TAOK3	0.004	0.001	-10000	0	0	4	4
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.004	-10000	0	-10000	0	0
MAP3K10	0.01	0	-10000	0	-10000	0	0
MAP3K3	0.01	0	-10000	0	-10000	0	0
TRX/ASK1	0.008	0.003	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.006	0.039	-10000	0	-0.086	12	12

×

PLK2 and PLK4 events

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.Total.Perturbations
PLK2	0.01	0.002	-9999	0	-9999	0
PLK4	0.01	0.002	-9999	0	-9999	0
regulation of centriole replication	-0.005	0.001	0	4	-9999	4

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.012	0.013	-10000	0	-0.1	1	1
ARNO/beta Arrestin1-2	0.016	0.013	-10000	0	-10000	0	0
EGFR	0.01	0.002	-10000	0	-10000	0	0
EPHA2	0.01	0.001	-10000	0	-10000	0	0
USP6	0.01	0	-10000	0	-10000	0	0
IQSEC1	0.01	0	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.001	0.036	-10000	0	-0.12	6	6
ARRB2	0.003	0.001	-10000	0	-10000	0	0
mol:GTP	0.002	0.037	0.078	2	-0.11	1	3
ARRB1	0.01	0	-10000	0	-10000	0	0
FBXO8	0.01	0	-10000	0	-10000	0	0
TSHR	0.006	0.005	-10000	0	-10000	0	0
EGF	0.007	0.005	-10000	0	-10000	0	0
somatostatin receptor activity	0	0	0	4	0	1	5
ARAP2	0.007	0.005	-10000	0	-10000	0	0
mol:GDP	0.009	0.036	0.14	2	-0.1	1	3
mol:PI-3-4-5-P3	0	0	0	2	-10000	0	2
ITGA2B	0.008	0.004	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.019	-10000	0	-0.093	2	2
ADAP1	0.01	0.002	-10000	0	-10000	0	0
KIF13B	0.01	0	-10000	0	-10000	0	0
HGF/MET	-0.001	0.044	-10000	0	-0.12	9	9
PXN	0.01	0	-10000	0	-10000	0	0
ARF6/GTP	0.013	0.051	0.16	4	-0.12	1	5
EGFR/EGFR/EGF/EGF/ARFGEP100	0.007	0.032	-10000	0	-0.1	6	6
ADRB2	0.01	0.002	-10000	0	-10000	0	0
receptor agonist activity	0	0	0	4	0	1	5
actin filament binding	0	0	0	4	0	1	5
SRC	0.01	0	-10000	0	-10000	0	0
ITGB3	0.01	0.002	-10000	0	-10000	0	0
GNAQ	0.01	0	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	0.001	5	-10000	0	5
ARF6/GDP	0.011	0.073	0.17	3	-0.18	2	5
ARF6/GDP/GULP/ACAP1	0.004	0.039	0.13	1	-10000	0	1
alphaIIb/beta3 Integrin/paxillin/GIT1	0.009	0.039	-10000	0	-0.093	10	10
ACAP1	0.008	0.004	-10000	0	-10000	0	0
ACAP2	0.01	0	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.002	0.003	-10000	0	-10000	0	0
EFNA1	0.01	0	-10000	0	-10000	0	0
HGF	0.008	0.004	-10000	0	-10000	0	0
CYTH3	-0.003	0.001	0.003	2	-10000	0	2
CYTH2	0.007	0.001	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
fibronectin binding	0	0	0	3	0	2	5
endosomal lumen acidification	0	0	0	6	0	1	7
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.009	0.004	-10000	0	-10000	0	0
GNAQ/ARNO	0.014	0.002	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	0	2	-10000	0	2
MET	0.01	0.002	-10000	0	-10000	0	0
GNA14	0.009	0.003	-10000	0	-10000	0	0
GNA15	0.01	0.001	-10000	0	-10000	0	0
GIT1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	5	-10000	0	5
GNA11	0.01	0	-10000	0	-10000	0	0
LHCGR	0.001	0.003	-10000	0	-10000	0	0
AGTR1	0.006	0.005	-10000	0	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.003	-10000	0	-10000	0	0
IPCEF1/ARNO	0.008	0.023	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.004	0.046	-10000	0	-0.12	10	10

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.003	0.079	-10000	0	-0.48	2	2
HDAC1	0.01	0	-10000	0	-10000	0	0
AES	0.01	0	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0.009	0.003	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0	-10000	0	-10000	0	0
TLE1	0.01	0.002	-10000	0	-10000	0	0
AP1	0.002	0.033	-10000	0	-0.28	1	1
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0.002	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.017	0.019	-10000	0	-10000	0	0
NICD/RBPSUH	0.005	0.072	-10000	0	-0.44	2	2
WIF1	0.003	0.004	-10000	0	-10000	0	0
NOTCH1	-0.002	0.074	-10000	0	-0.47	2	2
PSENEN	0.01	0	-10000	0	-10000	0	0
KREMEN2	0.008	0.004	-10000	0	-10000	0	0
DKK1	0.007	0.005	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.003	0.036	-10000	0	-0.19	1	1
APH1B	0.01	0	-10000	0	-10000	0	0
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	0.001	0.028	-10000	0	-0.17	2	2
CtBP/CBP/TCF1/TLE1/AES	0.003	0.024	-10000	0	-10000	0	0
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	0.009	0.003	-10000	0	-10000	0	0
JUN	0.01	0.002	-10000	0	-10000	0	0
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	-0.001	0.036	-10000	0	-0.2	1	1
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.001	0.042	-10000	0	-0.11	9	9
HNF1A	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
MYC	0.006	0.004	-10000	0	-10000	0	0
NKD1	0.01	0.002	-10000	0	-10000	0	0
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.003	0.072	-10000	0	-0.44	2	2
apoptosis	0.002	0.033	-10000	0	-0.28	1	1
Delta 1/NOTCHprecursor	0.002	0.077	-10000	0	-0.48	2	2
DLL1	0.009	0.004	-10000	0	-10000	0	0
PPARD	0.006	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.031	0	-10000	0	-10000	0	0
APC	0.001	0.028	-10000	0	-10000	0	0
DVL1	-0.003	0.032	-10000	0	-0.26	1	1
CSNK2A1	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.001	0.041	-10000	0	-0.1	11	11
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.004	0.001	-10000	0	-10000	0	0
CCND1	0.006	0.004	-10000	0	-10000	0	0
WNT1	0.005	0.005	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.002	0.038	-10000	0	-0.28	1	1
DKK2	0.007	0.005	-10000	0	-10000	0	0
NOTCH1 precursor/DVL1	0.001	0.084	-10000	0	-0.5	2	2
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.01	0	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.005	0.073	-10000	0	-0.45	2	2
PPP2R5D	-0.001	0.039	0.13	1	-0.21	2	3
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.007	0.044	-10000	0	-0.091	17	17
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.011	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.005	0.037	-9999	-0.091	10	10
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.001	0.013	-9999	-10000	0	0
AURKB	0.009	0.003	-9999	-10000	0	0
AURKC	0.009	0.003	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.005	0.093	0.17	2	-0.17	13	15
CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.01	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.01	0.097	0.18	2	-0.19	12	14
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	-0.005	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0.001	-10000	0	-10000	0	0
SNARE/Synip	0.018	0.019	-10000	0	-0.1	2	2
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	0.006	0.005	-10000	0	-10000	0	0
PRKCI	0.01	0.001	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.002	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.002	-10000	0	-10000	0	0
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.014	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.005	0.041	-10000	0	-0.14	6	6
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	-0.012	0.1	0.19	2	-0.21	12	14
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.007	0	-10000	0	-10000	0	0
SFN	0.007	0.005	-10000	0	-10000	0	0
LNPEP	0.01	0.001	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	-0.009	0.025	-10000	0	-0.21	1	1
FRAP1	0.001	0.006	-10000	0	-10000	0	0
AKT1	-0.007	0.023	-10000	0	-0.18	1	1
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.007	0.002	-10000	0	-10000	0	0
mol:GTP	0.005	0.022	-10000	0	-0.14	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.004	0.012	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	0.005	0.02	-10000	0	-0.13	1	1
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.006	0.028	-10000	0	-0.24	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.007	0.014	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.001	0.014	-10000	0	-10000	0	0
MAP3K5	-0.025	0.09	0.19	2	-0.25	10	12
PIK3R1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.025	0.09	0.18	2	-0.25	10	12
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	-0.001	0.012	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.011	0.014	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0.006	0.01	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.01	0.03	-10000	0	-0.22	1	1
mTOR/RHEB/GTP/Raptor/GBL	-0.004	0.009	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	0.009	0.021	-10000	0	-0.13	1	1
mol:Amino Acids	0	0	-10000	0	-0.001	1	1
FKBP12/Rapamycin	0.007	0	-10000	0	-10000	0	0
PDPK1	-0.01	0.023	-10000	0	-0.19	1	1
EIF4E	0.01	0.001	-10000	0	-10000	0	0
ASK1/PP5C	-0.056	0.19	-10000	0	-0.56	10	10
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.001	0.035	-10000	0	-0.31	1	1
TSC1/TSC2	0.006	0.023	-10000	0	-0.15	1	1
tumor necrosis factor receptor activity	0	0	0.001	1	-10000	0	1
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	-0.001	0.029	-10000	0	-0.26	1	1
INS	0.001	0.002	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0
PDK2	-0.01	0.023	-10000	0	-0.19	1	1
EIF4EBP1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PPP2R5D	0	0.006	-10000	0	-10000	0	0
peptide biosynthetic process	0.008	0.021	0.14	2	-10000	0	2
RHEB	0.01	0	-10000	0	-10000	0	0
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.008	0.021	0.14	2	-10000	0	2
eIF4E/4E-BP1	0.015	0.002	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.002	0.037	0.12	6	-10000	0	6
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.012	0.013	-10000	0	-0.1	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.009	0.003	-10000	0	-10000	0	0
RhoA/GTP	0.002	0.038	-10000	0	-0.13	6	6
negative regulation of cAMP metabolic process	-0.003	0.039	-10000	0	-0.14	6	6
GNAZ	0.01	0.002	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	0.009	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.003	0.039	-10000	0	-0.14	6	6
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.01	0.002	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0	0.036	-10000	0	-10000	0	0
NFATC2	-0.009	0.053	0.12	1	-0.2	3	4
NFATC3	0.001	0.037	-10000	0	-0.23	2	2
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.001	0.071	0.17	3	-0.28	2	5
Exportin 1/Ran/NUP214	0.018	0.019	-10000	0	-0.1	2	2
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.006	0.064	0.11	2	-0.24	2	4
BCL2/BAX	0.015	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.007	0.002	-10000	0	-10000	0	0
CaM/Ca2+	0.007	0.002	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0.002	-10000	0	-0.008	1	1
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.004	0.068	0.15	3	-0.22	3	6
Calcineurin A alpha-beta B1/BCL2	0.01	0	-10000	0	-10000	0	0
FKBP8	0.01	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.004	0.067	0.21	3	-0.15	3	6
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.01	0	-10000	0	-10000	0	0
XPO1	0.01	0.002	-10000	0	-10000	0	0
SFN	0.007	0.005	-10000	0	-10000	0	0
MAP3K8	0.01	0.003	-10000	0	-0.009	1	1
NFAT4/CK1 alpha	0.007	0.019	-10000	0	-0.089	3	3
MEF2D/NFAT1/Cbp/p300	0.007	0.056	0.11	1	-0.19	3	4
CABIN1	-0.001	0.071	0.17	3	-0.23	3	6
CALM1	0.01	0.002	-10000	0	-0.011	1	1
RAN	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0.008	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0.001	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.005	0.033	-10000	0	-0.12	5	5
YWHAB	0.01	0.001	-10000	0	-10000	0	0
MAPK8	0.009	0.003	-10000	0	-0.009	1	1
MAPK9	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.003	0.047	-10000	0	-0.22	2	2
PRKCH	0.01	0.001	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.015	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.002	-10000	0	-0.008	1	1
PIM1	0.01	0.002	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.001	-10000	0	-10000	0	0
apoptosis	0.008	0	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.036	-10000	0	-0.12	6	6
PRKCB	0.009	0.004	-10000	0	-10000	0	0
PRKCE	0.01	0.001	-10000	0	-10000	0	0
JNK2/NFAT4	0.007	0.034	-10000	0	-0.21	2	2
BAD/BCL-XL	0.015	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.003	-10000	0	-0.009	1	1
PRKCA	0.01	0	-10000	0	-10000	0	0
PRKCG	0.003	0.005	-10000	0	-10000	0	0
PRKCQ	0.009	0.004	-10000	0	-10000	0	0
FKBP38/BCL2	0.015	0	-10000	0	-10000	0	0
EP300	0.01	0.003	-10000	0	-0.016	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
NFATc/JNK1	0.006	0.035	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.013	0.003	-10000	0	-10000	0	0
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	-0.005	0.001	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.038	-10000	0	-0.1	10	10
NFATc/ERK1	0.006	0.036	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.006	0.064	0.11	2	-0.24	2	4
NR4A1	-0.009	0.05	-10000	0	-0.2	3	3
GSK3B	0.01	0.002	-10000	0	-0.009	1	1
positive T cell selection	0.001	0.036	-10000	0	-0.23	2	2
NFAT1/CK1 alpha	-0.008	0.043	-10000	0	-0.21	2	2
RCH1/ KPNB1	0.015	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0.002	-10000	0	-0.008	1	1
AKAP5	0.008	0.004	-10000	0	-10000	0	0
MEF2D	0.01	0.003	-10000	0	-0.016	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.006	0.036	-10000	0	-10000	0	0
CREBBP	0.01	0.003	-10000	0	-0.016	1	1
BCL2	0.01	0	-10000	0	-10000	0	0

×

FoxO family 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
G6PC	0.003	0.008	-10000	0	-10000	0	0
PLK1	-0.059	0.27	-10000	0	-0.91	5	5
CDKN1B	0.005	0.072	-10000	0	-10000	0	0
FOXO3	-0.03	0.19	-10000	0	-0.49	2	2
KAT2B	0.008	0.024	0.083	1	-10000	0	1
FOXO1/SIRT1	0.011	0.015	-10000	0	-10000	0	0
CAT	-0.027	0.17	-10000	0	-0.49	1	1
CTNNB1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.007	0.025	-10000	0	-10000	0	0
FOXO1	0.003	0.009	-10000	0	-10000	0	0
MAPK10	0.003	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.001	0.055	-10000	0	-10000	0	0
response to oxidative stress	0.001	0.02	-10000	0	-10000	0	0
FOXO3A/SIRT1	-0.036	0.14	0.35	1	-0.4	7	8
XPO1	0.01	0.002	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
BCL2L11	-0.01	0.13	-10000	0	-1.1	1	1
FOXO1/SKP2	0.008	0.01	-10000	0	-10000	0	0
mol:GDP	0.001	0.02	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
GADD45A	-0.004	0.077	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.005	0.046	-10000	0	-0.26	1	1
MST1	0.008	0.024	0.083	1	-10000	0	1
CSNK1D	0.01	0	-10000	0	-10000	0	0
CSNK1E	0.01	0	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.001	0.061	-10000	0	-0.21	6	6
YWHAB	0.01	0.001	-10000	0	-10000	0	0
MAPK8	0.004	0.01	-10000	0	-10000	0	0
MAPK9	0.004	0.011	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
SIRT1	0.007	0.027	0.058	8	-0.05	11	19
SOD2	-0.006	0.1	-10000	0	-10000	0	0
RBL2	-0.017	0.14	-10000	0	-10000	0	0
RAL/GDP	0.013	0.017	-10000	0	-10000	0	0
CHUK	0.007	0.025	0.083	1	-10000	0	1
Ran/GTP	0.008	0	-10000	0	-10000	0	0
CSNK1G2	0.01	0	-10000	0	-10000	0	0
RAL/GTP	0.014	0.016	-10000	0	-10000	0	0
CSNK1G1	0.01	0	-10000	0	-10000	0	0
FASLG	-0.029	0.38	0.52	11	-1.1	7	18
SKP2	0.01	0.001	-10000	0	-10000	0	0
USP7	0.01	0	-10000	0	-10000	0	0
IKBKB	0.007	0.025	0.083	1	-10000	0	1
CCNB1	-0.034	0.2	-10000	0	-1.1	1	1
FOXO1-3a-4/beta catenin	-0.003	0.11	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.01	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
SGK1	0.006	0.022	0.083	1	-10000	0	1
CSNK1G3	0.01	0.001	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.012	0.018	-10000	0	-0.1	2	2
ZFAND5	0.001	0.048	-10000	0	-10000	0	0
SFN	0.007	0.005	-10000	0	-10000	0	0
CDK2	0.01	0.002	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.004	0.074	-10000	0	-0.25	4	4
CREBBP	0.01	0.002	-10000	0	-10000	0	0
FBXO32	-0.041	0.23	0.52	1	-1	2	3
BCL6	-0.017	0.14	-10000	0	-10000	0	0
RALB	0.01	0	-10000	0	-10000	0	0
RALA	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.004	0.019	0.16	1	-10000	0	1
SNTA1	0.01	0.002	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.004	0.019	0.16	1	-10000	0	1
MAPK12	-0.003	0.001	-10000	0	-10000	0	0
CCND1	0.003	0.001	-10000	0	-10000	0	0
p38 gamma/SNTA1	-0.003	0.03	-10000	0	-0.15	2	2
MAP2K3	0.01	0	-10000	0	-10000	0	0
PKN1	0.01	0	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.004	0.016	-10000	0	-0.15	1	1
MAP2K6	-0.001	0	-10000	0	-10000	0	0
MAPT	-0.013	0.057	0.1	2	-0.17	6	8
MAPK13	-0.005	0.001	0	6	-10000	0	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.004	0.001	-10000	0	0	1	1

×

Canonical Wnt signaling pathway

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
HDAC1	0.01	0.01	0.081	1	-0.04	1	2
AES	0.01	0.008	0.069	1	-0.035	1	2
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.015	0	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	0.007	0.005	-10000	0	-10000	0	0
TLE1	0.009	0.009	0.07	1	-0.035	1	2
MACF1	0.01	0	-10000	0	-10000	0	0
CTNNB1	0.012	0.07	0.16	2	-0.19	2	4
WIF1	0.003	0.004	-10000	0	-10000	0	0
beta catenin/RanBP3	-0.012	0.06	0.36	1	-10000	0	1
KREMEN2	0.008	0.004	-10000	0	-10000	0	0
DKK1	0.007	0.005	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.015	0.068	0.15	2	-0.18	2	4
FZD1	0.01	0	-10000	0	-10000	0	0
AXIN2	-0.005	0.14	0.51	1	-1.1	1	2
AXIN1	0.01	0	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.03	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.01	0.045	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.008	0.038	-10000	0	-0.2	1	1
Axin1/APC/GSK3/beta catenin/Macf1	0.012	0.024	-10000	0	-10000	0	0
HNF1A	0.01	0.009	0.072	1	-0.036	1	2
CTBP1	0.01	0.009	0.074	1	-0.036	1	2
MYC	0.001	0.028	-10000	0	-10000	0	0
RANBP3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.002	0.042	-10000	0	-0.11	9	9
NKD1	0.01	0.002	-10000	0	-10000	0	0
TCF4	0.009	0.009	0.073	1	-0.036	1	2
TCF3	0.01	0.009	0.072	1	-0.036	1	2
WNT1/LRP6/FZD1/Axin1	0.023	0.003	-10000	0	-10000	0	0
Ran/GTP	0.007	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.001	0.074	0.4	1	-0.34	1	2
LEF1	0.009	0.009	0.073	1	-0.036	1	2
DVL1	-0.004	0.035	-10000	0	-0.29	1	1
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.008	0.063	-10000	0	-0.4	1	1
DKK1/LRP6/Kremen 2	-0.001	0.041	-10000	0	-0.1	11	11
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.01	0.08	1	-0.04	1	2
NLK	0.01	0.003	-10000	0	-0.015	1	1
CCND1	0.001	0.028	-10000	0	-10000	0	0
WNT1	0.005	0.005	-10000	0	-0.002	1	1
GSK3A	0.01	0	-10000	0	-10000	0	0
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.006	0.043	0.16	1	-0.2	2	3
APC	-0.006	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.002	0.016	-10000	0	-0.13	1	1
CREBBP	0.01	0.009	0.072	1	-0.036	1	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.014	0	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.01	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.004	0.002	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.01	0	-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	0.01	0	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
MAP3K12	0.01	0.001	-10000	0	-10000	0	0
FGR	0.008	0.004	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.029	0.047	-10000	0	-0.15	5	5
PRKG1	0.009	0.004	-10000	0	-10000	0	0
DUSP8	0.01	0.002	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	-0.018	0.058	-10000	0	-0.16	5	5
apoptosis	-0.028	0.045	-10000	0	-0.15	5	5
RAL/GTP	0.014	0	-10000	0	-10000	0	0
LYN	0.01	0	-10000	0	-10000	0	0
DUSP1	0.01	0.001	-10000	0	-10000	0	0
PAK1	0.01	0	-10000	0	-10000	0	0
SRC	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.027	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-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	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.014	0	-10000	0	-10000	0	0
MAPK11	-0.006	0.087	0.18	2	-0.18	6	8
BLK	0.007	0.005	-10000	0	-10000	0	0
HCK	0.01	0.002	-10000	0	-10000	0	0
MAP2K3	0.01	0	-10000	0	-10000	0	0
DUSP16	0.01	0	-10000	0	-10000	0	0
DUSP10	0.009	0.003	-10000	0	-10000	0	0
TRAF6/MEKK3	0.013	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.005	0.074	0.15	2	-0.16	5	7
positive regulation of innate immune response	-0.007	0.096	0.2	2	-0.22	5	7
LCK	0.006	0.005	-10000	0	-10000	0	0
p38alpha-beta/MKP7	-0.004	0.095	0.19	2	-0.21	5	7
p38alpha-beta/MKP5	-0.006	0.094	0.19	2	-0.2	6	8
PGK/cGMP	-0.001	0.031	-10000	0	-0.12	5	5
PAK2	0.01	0	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.003	0.094	0.19	2	-0.21	5	7
CDC42	0.01	0	-10000	0	-10000	0	0
RALB	0.01	0	-10000	0	-10000	0	0
RALA	0.01	0	-10000	0	-10000	0	0
PAK3	0.007	0.005	-10000	0	-10000	0	0

×

TCGA08_rtk_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
PDGFRA	0.007	0.005	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	0.01	0.002	-10000	0	-10000	0	0
AKT	0.009	0.06	0.17	3	-0.11	4	7
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
AKT3	0.01	0	-10000	0	-10000	0	0
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	0.01	0.002	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
PIK3CG	0.009	0.004	-10000	0	-10000	0	0
PIK3R3	0.01	0.002	-10000	0	-10000	0	0
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.01	0	-10000	0	-10000	0	0
RAS	0.018	0.032	0.087	13	-10000	0	13
ERBB2	0.01	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.014	0.023	-10000	0	-10000	0	0
PI3K	0.02	0.047	0.16	4	-0.1	2	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0.001	-10000	0	-10000	0	0
FOXO	0.032	0.035	0.14	4	-10000	0	4
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.011	0.03	0.1	1	-0.089	1	2
DAPP1	0.03	0.14	0.35	2	-0.25	1	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.006	0.24	0.37	3	-0.38	4	7
mol:DAG	0.041	0.14	0.28	4	-0.14	4	8
HRAS	0.009	0.006	-10000	0	-0.015	1	1
RAP1A	0.009	0.006	-10000	0	-0.015	1	1
ARF5/GDP	0.006	0.052	-10000	0	-0.16	1	1
PLCG2	0.01	0	-10000	0	-10000	0	0
PLCG1	0.01	0	-10000	0	-10000	0	0
ARF5	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.014	0.017	-10000	0	-0.091	1	1
ARF1/GTP	-0.007	0.03	0.1	1	-10000	0	1
RHOA	0.01	0	-10000	0	-10000	0	0
YES1	0.01	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.014	0.017	-10000	0	-0.09	1	1
ADAP1	-0.014	0.017	-10000	0	-0.088	1	1
ARAP3	-0.014	0.017	-10000	0	-0.089	1	1
INPPL1	0.01	0	-10000	0	-10000	0	0
PREX1	0.01	0	-10000	0	-10000	0	0
ARHGEF6	0.009	0.003	-10000	0	-10000	0	0
ARHGEF7	0.01	0	-10000	0	-10000	0	0
ARF1	0.01	0	-10000	0	-10000	0	0
NRAS	0.009	0.006	-10000	0	-0.015	1	1
FYN	0.01	0	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
FGR	0.008	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.028	0.093	0.18	4	-0.081	2	6
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.01	0.002	-10000	0	0	1	1
ZAP70	0.006	0.005	-10000	0	0	8	8
mol:IP3	0.03	0.11	0.22	4	-0.099	4	8
LYN	0.01	0	-10000	0	-10000	0	0
ARF1/GDP	0.006	0.052	-10000	0	-0.16	1	1
RhoA/GDP	0.004	0.037	-10000	0	-0.14	1	1
PDK1/Src/Hsp90	0.021	0	-10000	0	-10000	0	0
BLNK	0.009	0.003	-10000	0	0	2	2
actin cytoskeleton reorganization	0.002	0.047	-10000	0	-0.15	1	1
SRC	0.01	0	-10000	0	-10000	0	0
PLEKHA2	0.009	0.049	0.16	2	-10000	0	2
RAC1	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0.005	-10000	0	-0.011	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
ARF6/GTP	-0.011	0.03	0.1	1	-0.089	1	2
RhoA/GTP	-0.015	0.017	-10000	0	-0.088	1	1
Src family/SYK family/BLNK-LAT	-0.043	0.12	-10000	0	-0.27	4	4
BLK	0.007	0.005	-10000	0	0	7	7
PDPK1	0.01	0	-10000	0	-10000	0	0
CYTH1	-0.01	0.031	0.11	1	-0.088	1	2
HCK	0.01	0.002	-10000	0	-10000	0	0
CYTH3	-0.01	0.031	0.11	1	-0.088	1	2
CYTH2	-0.01	0.031	0.11	1	-0.088	1	2
KRAS	0.01	0.003	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.046	0.13	-10000	0	-0.35	3	3
SGK1	-0.047	0.13	-10000	0	-0.37	3	3
INPP5D	0.009	0.003	-10000	0	-10000	0	0
mol:GDP	0	0.052	-10000	0	-0.16	1	1
SOS1	0.01	0	-10000	0	-10000	0	0
SYK	0.01	0.002	-10000	0	-10000	0	0
ARF6/GDP	-0.01	0.035	-10000	0	-0.14	1	1
mol:PI-3-4-5-P3	-0.009	0.032	0.11	1	-0.091	1	2
ARAP3/RAP1A/GTP	-0.014	0.017	-10000	0	-0.091	1	1
VAV1	0.009	0.003	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.005	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.014	0.033	0.12	1	-0.092	1	2
PLEKHA1	0.017	0.058	0.16	3	-10000	0	3
Rac1/GDP	0.006	0.052	-10000	0	-0.16	1	1
LAT	0.008	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.009	0.068	-10000	0	-0.21	2	2
ITK	-0.006	0.031	0.11	1	-0.088	1	2
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.04	0.17	0.31	4	-0.18	4	8
LCK	0.005	0.005	-10000	0	0	1	1
BTK	-0.009	0.031	0.11	1	-0.088	1	2

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.021	0.077	0.49	1	-10000	0	1
RAD9A	0.01	0	-10000	0	-10000	0	0
AP1	0.006	0.041	0.075	1	-0.14	5	6
IFNAR2	0.011	0.006	0.061	1	-10000	0	1
AKT1	-0.009	0.034	-10000	0	-10000	0	0
ER alpha/Oestrogen	-0.01	0.044	-10000	0	-0.12	11	11
NFX1/SIN3/HDAC complex	0.007	0.029	-10000	0	-0.13	3	3
EGF	0.007	0.005	-10000	0	-10000	0	0
SMG5	0.01	0	-10000	0	-10000	0	0
SMG6	0.01	0	-10000	0	-10000	0	0
SP3/HDAC2	0.015	0.018	0.1	1	-0.12	1	2
TERT/c-Abl	0.015	0.056	-10000	0	-10000	0	0
SAP18	0.01	0.001	0.02	1	-10000	0	1
MRN complex	0.017	0.027	-10000	0	-0.15	2	2
WT1	0.003	0.008	0.061	1	-10000	0	1
WRN	0.01	0.001	-10000	0	-10000	0	0
SP1	0.012	0.008	0.083	1	-10000	0	1
SP3	0.011	0.003	0.036	1	-10000	0	1
TERF2IP	0.01	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.013	0.047	-10000	0	-10000	0	0
Mad/Max	0.016	0.007	0.075	1	-10000	0	1
TERT	0.021	0.078	0.5	1	-10000	0	1
CCND1	0.022	0.072	0.46	1	-10000	0	1
MAX	0.011	0.003	0.035	1	-10000	0	1
RBBP7	0.01	0.001	0.02	1	-10000	0	1
RBBP4	0.01	0.001	0.02	1	-10000	0	1
TERF2	0.012	0.012	0.066	4	-10000	0	4
PTGES3	0.01	0	-10000	0	-10000	0	0
SIN3A	0.01	0.001	0.02	1	-10000	0	1
Telomerase/911	0.016	0.02	-10000	0	-10000	0	0
CDKN1B	0	0.033	0.14	2	-10000	0	2
RAD1	0.01	0	-10000	0	-10000	0	0
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
SAP30	0.01	0.002	0.02	1	-10000	0	1
TRF2/PARP2	0.017	0.01	0.061	4	-10000	0	4
UBE3A	0.011	0.002	0.032	1	-10000	0	1
JUN	0.01	0.003	0.035	1	-10000	0	1
E6	0	0.002	0.022	1	-10000	0	1
HPV-16 E6/E6AP	0.009	0.006	0.061	1	-10000	0	1
FOS	0.01	0.004	0.035	1	-10000	0	1
IFN-gamma/IRF1	0.007	0.032	-10000	0	-0.12	4	4
PARP2	0.01	0	-10000	0	-10000	0	0
BLM	0.01	0.001	-10000	0	-10000	0	0
Telomerase	0	0.055	-10000	0	-0.25	1	1
IRF1	0.01	0.005	-10000	0	-10000	0	0
ESR1	0.008	0.004	-10000	0	-10000	0	0
KU/TER	0.015	0	-10000	0	-10000	0	0
ATM/TRF2	0.007	0.034	-10000	0	-0.14	4	4
ubiquitin-dependent protein catabolic process	0.009	0.027	-10000	0	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.009	0.027	-10000	0	-10000	0	0
HDAC1	0.01	0.001	0.02	1	-10000	0	1
HDAC2	0.011	0.007	0.072	1	-10000	0	1
ATM	-0.008	0.051	-10000	0	-0.23	4	4
SMAD3	-0.006	0.003	-10000	0	-0.035	1	1
ABL1	0.01	0	-10000	0	-10000	0	0
MXD1	0.011	0.003	0.035	1	-10000	0	1
MRE11A	0.01	0.002	-10000	0	-10000	0	0
HUS1	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.016	0.057	-10000	0	-10000	0	0
NR2F2	0.009	0.007	-10000	0	-0.05	1	1
MAPK3	-0.002	0.006	0.047	1	-10000	0	1
MAPK1	-0.002	0.006	0.047	1	-10000	0	1
TGFB1/TGF beta receptor Type II	0.009	0.004	-10000	0	-0.024	1	1
NFKB1	0.01	0	-10000	0	-10000	0	0
HNRNPC	0.01	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.008	0.051	-10000	0	-0.23	4	4
NBN	0.01	0	-10000	0	-10000	0	0
EGFR	0.01	0.003	0.03	1	-10000	0	1
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	0.002	0.037	-10000	0	-0.12	6	6
MYC	0.011	0.003	0.041	1	-10000	0	1
IL2	0.002	0.008	0.072	1	-10000	0	1
KU	0.015	0	-10000	0	-10000	0	0
RAD50	0.01	0.001	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
TGFB1	0.009	0.004	-10000	0	-0.024	1	1
TRF2/BLM	0.015	0.018	0.061	4	-0.12	1	5
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.027	0.072	0.43	1	-10000	0	1
SP1/HDAC2	0.018	0.015	0.15	1	-10000	0	1
PINX1	0.01	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.013	0.047	-10000	0	-10000	0	0
Smad3/Myc	0.007	0.018	-10000	0	-0.1	2	2
911 complex	0.021	0	-10000	0	-10000	0	0
IFNG	0.005	0.006	-10000	0	-10000	0	0
Telomerase/PinX1	0.013	0.047	-10000	0	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.007	0.03	0.2	1	-10000	0	1
SIN3B	0.01	0.001	0.02	1	-10000	0	1
YWHAE	0.01	0	-10000	0	-10000	0	0
Telomerase/EST1B	0.013	0.047	-10000	0	-10000	0	0
response to DNA damage stimulus	-0.004	0.024	-10000	0	-0.11	4	4
MRN complex/TRF2/Rap1	0.027	0.022	-10000	0	-0.1	2	2
TRF2/WRN	0.015	0.014	0.061	3	-0.082	1	4
Telomerase/hnRNP C1/C2	0.013	0.047	-10000	0	-10000	0	0
E2F1	0.011	0.006	0.061	1	-10000	0	1
ZNFX1	0.01	0.002	0.02	1	-10000	0	1
PIF1	0.01	0.002	-10000	0	-10000	0	0
NCL	0.01	0	-10000	0	-10000	0	0
DKC1	0.01	0	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Insulin 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
CBL/APS/CAP	0.015	0.016	-10000	0	-0.083	2	2
TC10/GTP	0.018	0.011	-10000	0	-0.082	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.018	0.013	-10000	0	-0.096	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
APS homodimer	0.01	0	-10000	0	-10000	0	0
GRB14	0.005	0.005	-10000	0	-10000	0	0
FOXO3	-0.053	0.16	-10000	0	-0.48	10	10
AKT1	-0.007	0.029	0.11	2	-10000	0	2
INSR	0.011	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.018	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.01	0.001	-10000	0	-10000	0	0
SORBS1	0.01	0.001	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
PTPN1	-0.004	0.018	0.11	2	-10000	0	2
CAV1	-0.004	0.021	0.11	2	-0.088	1	3
CBL/APS/CAP/Crk-II/C3G	0.029	0.013	-10000	0	-0.088	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.018	0.013	-10000	0	-0.096	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.013	0.019	-10000	0	-0.083	3	3
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.008	0.002	-10000	0	-10000	0	0
RPS6KB1	-0.008	0.028	0.11	2	-10000	0	2
PARD6A	0.01	0.002	-10000	0	-10000	0	0
CBL	0.01	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.009	0.004	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.015	0.013	-10000	0	-10000	0	0
HRAS/GTP	-0.013	0.015	-10000	0	-0.079	4	4
Insulin Receptor	0.011	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.023	0.013	-10000	0	-0.09	1	1
PRKCI	0.006	0.042	-10000	0	-0.37	1	1
Insulin Receptor/Insulin/GRB14/PDK1	0.007	0.017	-10000	0	-0.08	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.017	0.02	-10000	0	-0.16	1	1
PI3K	0.017	0.02	-10000	0	-0.084	3	3
NCK2	0.01	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
mol:H2O2	-0.001	0	-10000	0	-10000	0	0
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
AKT2	-0.007	0.029	0.11	4	-10000	0	4
PRKCZ	0.002	0.059	-10000	0	-0.36	2	2
SH2B2	0.01	0	-10000	0	-10000	0	0
SHC/SHIP	0.009	0.024	0.11	2	-0.083	3	5
F2RL2	0.006	0.005	-10000	0	-10000	0	0
TRIP10	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.014	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.023	0.013	-10000	0	-0.089	1	1
RAPGEF1	0.01	0	-10000	0	-10000	0	0
RASA1	0.01	0.001	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.025	0.013	-10000	0	-0.093	1	1
TC10/GDP	0.008	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.019	0.013	-10000	0	-0.095	1	1
INPP5D	-0.002	0.019	0.11	2	-10000	0	2
SOS1	0.01	0.001	-10000	0	-10000	0	0
SGK1	-0.083	0.23	-10000	0	-0.7	10	10
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.01	0	-10000	0	-10000	0	0
IRS1	0.01	0.001	-10000	0	-10000	0	0
p62DOK/RasGAP	0.017	0.02	-10000	0	-0.16	1	1
INS	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.002	0.019	0.11	2	-10000	0	2
GRB2	0.01	0	-10000	0	-10000	0	0
EIF4EBP1	-0.008	0.028	0.11	2	-10000	0	2
PTPRA	0.011	0.002	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.014	0	-10000	0	-10000	0	0
PDPK1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.004	0.023	-10000	0	-0.14	2	2
Insulin Receptor/Insulin/IRS1	0.012	0.012	-10000	0	-0.094	1	1
Insulin Receptor/Insulin/IRS3	0.008	0.002	-10000	0	-10000	0	0
Par3/Par6	0.004	0.039	-10000	0	-0.086	12	12

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.012	0.013	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.004	0.012	-10000	0	-10000	0	0
mol:DAG	0	0.042	0.26	2	-10000	0	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.008	0.02	-10000	0	-10000	0	0
CaM/Ca2+	0.005	0.021	-10000	0	-10000	0	0
HIF1A	0.014	0.003	-10000	0	-10000	0	0
GAB1	0.01	0	-10000	0	-10000	0	0
AKT1	-0.005	0.05	0.22	2	-10000	0	2
PLCG1	0	0.042	0.26	2	-10000	0	2
NOS3	0.003	0.055	0.22	2	-0.23	1	3
CBL	0.01	0	-10000	0	-10000	0	0
mol:NO	0.003	0.054	0.22	2	-0.22	1	3
FLT1	0.016	0.051	0.34	2	-10000	0	2
PGF	0.01	0.002	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.009	0.031	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
eNOS/Hsp90	0.009	0.053	0.22	2	-0.22	1	3
endothelial cell proliferation	0.004	0.077	0.34	2	-0.27	1	3
mol:Ca2+	0	0.042	0.26	2	-10000	0	2
MAPK3	-0.003	0.046	0.18	4	-10000	0	4
MAPK1	-0.003	0.046	0.18	4	-10000	0	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
PLGF homodimer	0.01	0.002	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.01	0.001	-10000	0	-10000	0	0
VEGFA homodimer	0.01	0.002	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.011	0.013	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.005	0.044	0.22	2	-10000	0	2
PI3K	0.015	0.03	-10000	0	-10000	0	0
PRKCA	0.002	0.045	0.19	4	-10000	0	4
PRKCB	0.006	0.065	0.26	4	-10000	0	4
VEGFR1 homodimer/PLGF homodimer	0.011	0.013	-10000	0	-10000	0	0
VEGFA	0.01	0.002	-10000	0	-10000	0	0
VEGFB	0.01	0	-10000	0	-10000	0	0
mol:IP3	0	0.042	0.26	2	-10000	0	2
RASA1	0.001	0.041	0.26	2	-10000	0	2
NRP2	0.01	0.002	-10000	0	-10000	0	0
VEGFR1 homodimer	0.016	0.051	0.34	2	-10000	0	2
VEGFB homodimer	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.008	0.053	0.22	2	-0.22	1	3
PTPN11	0.01	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.014	0.029	-10000	0	-10000	0	0
mol:L-citrulline	0.003	0.054	0.22	2	-0.22	1	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.019	0.022	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.013	0.028	-10000	0	-0.18	1	1
CD2AP	0.01	0	-10000	0	-10000	0	0
PI3K/GAB1	0.019	0.03	-10000	0	-10000	0	0
PDPK1	-0.005	0.047	0.23	2	-10000	0	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.014	0.021	-10000	0	-10000	0	0
mol:NADP	0.003	0.054	0.22	2	-0.22	1	3
HSP90AA1	0.01	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.019	0.021	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.011	0.013	-10000	0	-10000	0	0

×

S1P3 pathway

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
PDGFRB	0.01	0	-10000	0	-10000	0	0
mol:S1P	0	0	-10000	0	-10000	0	0
S1P1/S1P/Gi	0	0.041	-10000	0	-0.14	6	6
GNAO1	0.01	0.003	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.017	0.018	-10000	0	-0.091	2	2
AKT1	0.009	0.013	-10000	0	-10000	0	0
AKT3	0.003	0.043	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.01	0	-10000	0	-10000	0	0
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.01	0.002	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.01	0.002	-10000	0	-10000	0	0
S1PR2	0.01	0	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.045	-10000	0	-0.14	7	7
MAPK3	-0.007	0.042	-10000	0	-0.13	5	5
MAPK1	-0.007	0.042	-10000	0	-0.13	8	8
JAK2	-0.001	0.046	0.16	1	-0.14	3	4
CXCR4	-0.004	0.036	-10000	0	-0.13	6	6
FLT1	0.01	0.002	-10000	0	-10000	0	0
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
Rac1/GDP	0.008	0	-10000	0	-10000	0	0
SRC	-0.007	0.042	-10000	0	-0.13	7	7
S1P/S1P3/Gi	-0.004	0.045	-10000	0	-0.14	8	8
RAC1	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0.001	0.043	-10000	0	-0.12	8	8
VEGFA	0.01	0.002	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.001	0.039	-10000	0	-0.14	6	6
VEGFR1 homodimer/VEGFA homodimer	0.012	0.022	-10000	0	-0.12	2	2
RHOA	0.01	0	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.002	0.036	-10000	0	-0.14	5	5
GNAQ	0.01	0	-10000	0	-10000	0	0
GNAZ	0.01	0.002	-10000	0	-10000	0	0
G12/G13	0.015	0	-10000	0	-10000	0	0
GNA14	0.009	0.003	-10000	0	-10000	0	0
GNA15	0.01	0.001	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.001	0.043	-10000	0	-0.12	8	8

×

Signaling events mediated by PRL

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
CCNE1	0.01	0	-10000	0	-10000	0	0
mol:Halofuginone	0.002	0	-10000	0	-10000	0	0
ITGA1	0.009	0.003	-10000	0	-10000	0	0
CDKN1A	-0.027	0.11	-10000	0	-0.38	7	7
PRL-3/alpha Tubulin	0.011	0.022	-10000	0	-0.12	2	2
mol:Ca2+	-0.007	0.004	-10000	0	-10000	0	0
AGT	0.008	0.004	-10000	0	-10000	0	0
CCNA2	0.01	0.042	-10000	0	-10000	0	0
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	0.004	0.002	-10000	0	-10000	0	0
CDK2/Cyclin E1	-0.006	0.11	-10000	0	-0.34	7	7
MAPK3	-0.005	0.002	0	8	-10000	0	8
PRL-2 /Rab GGTase beta	0.015	0	-10000	0	-10000	0	0
MAPK1	-0.005	0.002	0	8	-10000	0	8
PTP4A1	0.015	0.048	-10000	0	-10000	0	0
PTP4A3	0.009	0.003	-10000	0	-10000	0	0
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	-0.005	0.002	0	8	-10000	0	8
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	-0.004	0.061	-10000	0	-0.38	2	2
Rab GGTase beta/Rab GGTase alpha	0.015	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.016	0.047	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	-0.002	0.04	0.25	2	-10000	0	2
RHOC	-0.004	0.061	-10000	0	-0.38	2	2
RHOA	-0.004	0.061	-10000	0	-0.38	2	2
cell motility	0.013	0.071	-10000	0	-0.38	2	2
PRL-1/alpha Tubulin	0.016	0.047	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.005	0.034	-10000	0	-0.12	5	5
ROCK1	0.013	0.072	-10000	0	-0.38	2	2
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.015	0.048	-10000	0	-10000	0	0
ATF5	0.01	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.001	0	-9999	-10000	0	0
SMAD3	0.005	0	-9999	-10000	0	0
SMAD3/SMAD4	0.014	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.021	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.024	0	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.008	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.014	0.015	-9999	-0.12	1	1
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.01	0.001	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.01	0	-9999	-10000	0	0
PIAS4	0.01	0	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.008	0.016	0.13	1	-10000	0	1
KIRREL	0.011	0.003	-10000	0	-10000	0	0
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.008	0.016	-10000	0	-0.13	1	1
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.013	0.012	-10000	0	-0.092	1	1
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.002	0.023	-10000	0	-0.14	2	2
FYN	0.006	0.02	0.11	2	-0.096	1	3
mol:Ca2+	0.012	0.012	-10000	0	-0.091	1	1
mol:DAG	0.012	0.012	-10000	0	-0.091	1	1
NPHS2	0	0.004	-10000	0	-0.021	1	1
mol:IP3	0.012	0.012	-10000	0	-0.091	1	1
regulation of endocytosis	0.014	0.012	-10000	0	-0.091	1	1
Nephrin/NEPH1/podocin/Cholesterol	0.006	0.011	-10000	0	-0.09	1	1
establishment of cell polarity	0.008	0.016	-10000	0	-0.13	1	1
Nephrin/NEPH1/podocin/NCK1-2	0.017	0.017	-10000	0	-0.088	2	2
Nephrin/NEPH1/beta Arrestin2	0.015	0.013	-10000	0	-0.092	1	1
NPHS1	0.002	0.006	-10000	0	-0.021	1	1
Nephrin/NEPH1/podocin	0.007	0.012	-10000	0	-0.096	1	1
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.013	0.012	-10000	0	-0.092	1	1
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.013	0.012	-10000	0	-0.092	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.003	0.02	0.11	2	-0.08	1	3
cytoskeleton organization	-0.007	0.018	-10000	0	-0.13	1	1
Nephrin/NEPH1	0.007	0.011	-10000	0	-0.082	1	1
Nephrin/NEPH1/ZO-1	0.014	0.013	-10000	0	-0.099	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.014	0.028	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	0.007	0.03	-9999	-0.12	4	4
NFKBIA	-0.009	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	0.01	0.04	-9999	-10000	0	0
IKK complex/A20	0.017	0.038	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0.002	-9999	-10000	0	0
NEMO/ATM	0.015	0.04	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.011	0.018	-9999	-0.1	2	2
IKK complex/ELKS	0.019	0.036	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.019	0.014	-9999	-0.1	1	1
NOD2	0.009	0.004	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
MALT1	0.01	0.001	-9999	-10000	0	0
cIAP1/UbcH5C	0.015	0	-9999	-10000	0	0
ATM	0.01	0.002	-9999	-10000	0	0
TNF/TNFR1A	0.01	0.016	-9999	-0.12	1	1
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.01	0	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	0.007	0.005	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.024	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.009	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0.021	0.04	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.024	0.039	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.023	0.019	-10000	0	-0.093	2	2
HDAC3	0.01	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.008	0.011	-10000	0	-0.075	2	2
GATA1/HDAC4	0.01	0.004	-10000	0	-10000	0	0
GATA1/HDAC5	0.01	0.004	-10000	0	-10000	0	0
GATA2/HDAC5	0.015	0.002	-10000	0	-10000	0	0
HDAC5/BCL6/BCoR	0.021	0	-10000	0	-10000	0	0
HDAC9	0.008	0.004	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.019	0.014	-10000	0	-0.1	1	1
HDAC4/ANKRA2	0.012	0.022	-10000	0	-0.12	2	2
HDAC5/YWHAB	0.014	0.015	-10000	0	-0.12	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.004	0	-10000	0	-10000	0	0
GATA2	0.01	0.001	-10000	0	-10000	0	0
HDAC4/RFXANK	0.015	0	-10000	0	-10000	0	0
BCOR	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.01	0	-10000	0	-10000	0	0
HDAC5	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	0.011	0.022	-10000	0	-0.12	2	2
Histones	-0.002	0.049	-10000	0	-0.13	9	9
ADRBK1	0.01	0	-10000	0	-10000	0	0
HDAC4	0.01	0	-10000	0	-10000	0	0
XPO1	0.01	0.002	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.012	0.022	-10000	0	-0.12	2	2
HDAC4/Ubc9	0.015	0	-10000	0	-10000	0	0
HDAC7	0.01	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.015	0	-10000	0	-10000	0	0
TUBA1B	0.01	0	-10000	0	-10000	0	0
HDAC6	0.01	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.015	0	-10000	0	-10000	0	0
CAMK4	0.008	0.004	-10000	0	-10000	0	0
Tubulin/HDAC6	0.021	0	-10000	0	-10000	0	0
SUMO1	0.01	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.01	0.001	-10000	0	-10000	0	0
GATA1	0.003	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
NR3C1	0.01	0.001	-10000	0	-10000	0	0
SUMO1/HDAC4	0.016	0	-10000	0	-10000	0	0
SRF	0.01	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.014	0.015	-10000	0	-0.12	1	1
Tubulin	0.015	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.015	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
RANGAP1	0.01	0	-10000	0	-10000	0	0
BCL6/BCoR	0.015	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.021	0	-10000	0	-10000	0	0
HDAC4/SRF	0.004	0.041	-10000	0	-0.1	10	10
HDAC4/ER alpha	-0.005	0.048	-10000	0	-0.12	11	11
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.002	0.049	-10000	0	-0.13	9	9
cell motility	0.021	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.01	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.015	0	-10000	0	-10000	0	0
BCL6	0.01	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.01	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0.015	0	-10000	0	-10000	0	0
ESR1	0.008	0.004	-10000	0	-10000	0	0
HDAC6/HDAC11	0.015	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.014	0.014	-10000	0	-10000	0	0
NPC	0.006	0	-10000	0	-10000	0	0
MEF2C	0.01	0.001	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.029	0.013	-10000	0	-0.088	1	1
GNG2	0.01	0.002	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
TUBB2A	0.01	0	-10000	0	-10000	0	0
HDAC11	0.01	0.001	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RANBP2	0.01	0	-10000	0	-10000	0	0
ANKRA2	0.01	0.002	-10000	0	-10000	0	0
RFXANK	0.01	0	-10000	0	-10000	0	0
nuclear import	-0.011	0.019	0.16	1	-10000	0	1

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.005	0.054	-10000	0	-0.23	2	2
epithelial cell differentiation	-0.007	0.051	-10000	0	-0.25	2	2
ITCH	0.009	0.014	0.066	1	-10000	0	1
WWP1	0.005	0.003	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
EGFR	0.01	0.002	-10000	0	-10000	0	0
PRL	0.005	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.004	0.056	0.28	1	-10000	0	1
PTPRZ1	0.007	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.014	0.05	-10000	0	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0	0.039	-10000	0	-10000	0	0
ADAM17	0.01	0.015	0.066	2	-10000	0	2
ErbB4/ErbB4	0.006	0.003	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0	0.064	-10000	0	-0.27	2	2
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.006	0.039	-10000	0	-10000	0	0
GRIN2B	0.006	0.05	-10000	0	-10000	0	0
ErbB4/ErbB2/betacellulin	0	0.036	-10000	0	-10000	0	0
STAT1	0.009	0.003	-10000	0	-10000	0	0
HBEGF	0.01	0	-10000	0	-10000	0	0
PRLR	0.008	0.004	-10000	0	-10000	0	0
E4ICDs/ETO2	0.003	0.054	-10000	0	-0.23	2	2
axon guidance	0.012	0.065	-10000	0	-0.31	1	1
NEDD4	0.009	0.013	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.001	0.035	-10000	0	-0.12	6	6
CBFA2T3	0.01	0.002	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.008	0.039	-10000	0	-10000	0	0
MAPK3	-0.001	0.058	0.28	1	-10000	0	1
STAT1 (dimer)	0.004	0.053	-10000	0	-0.23	2	2
MAPK1	-0.001	0.058	0.28	1	-10000	0	1
JAK2	0.01	0.002	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.003	0.042	-10000	0	-10000	0	0
NRG1	-0.003	0.01	0.04	2	-10000	0	2
NRG3	0.009	0.003	-10000	0	-10000	0	0
NRG2	0.01	0.002	-10000	0	-10000	0	0
NRG4	0.007	0.005	-10000	0	-10000	0	0
heart development	0.012	0.065	-10000	0	-0.31	1	1
neural crest cell migration	0.003	0.041	-10000	0	-10000	0	0
ERBB2	-0.003	0.011	0.04	2	-10000	0	2
WWOX/E4ICDs	0.004	0.054	-10000	0	-0.23	2	2
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.005	0.051	-10000	0	-0.21	2	2
apoptosis	0.026	0.11	0.31	9	-10000	0	9
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.003	0.053	-10000	0	-0.23	2	2
ErbB4/ErbB2/epiregulin	-0.004	0.033	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.005	0.05	-10000	0	-0.23	2	2
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.004	0.061	-10000	0	-10000	0	0
MDM2	-0.006	0.03	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0	0.034	-10000	0	-0.2	1	1
STAT5A	0.009	0.063	-10000	0	-0.29	1	1
ErbB4/EGFR/neuregulin 1 beta	0.006	0.038	-10000	0	-10000	0	0
DLG4	0.01	0.002	-10000	0	-10000	0	0
GRB2/SHC	0.015	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.004	0.05	-10000	0	-0.21	2	2
STAT5A (dimer)	0.004	0.063	-10000	0	-0.27	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.016	0.064	-10000	0	-0.29	1	1
LRIG1	0.01	0.001	-10000	0	-10000	0	0
EREG	0.001	0.003	-10000	0	-10000	0	0
BTC	0.006	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.007	0.062	-10000	0	-0.31	1	1
ERBB4	0.006	0.003	-10000	0	-10000	0	0
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	0.007	0.01	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.004	0.038	-10000	0	-10000	0	0
glial cell differentiation	-0.004	0.049	0.21	2	-10000	0	2
WWOX	0.01	0.001	-10000	0	-10000	0	0
cell proliferation	0.027	0.06	0.29	1	-10000	0	1

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.01	0	-9999	0	-10000	0	0
SPHK1	0.01	0.002	-9999	0	-10000	0	0
GNAI2	0.01	0	-9999	0	-10000	0	0
mol:S1P	0.004	0.001	-9999	0	-10000	0	0
GNAO1	0.009	0.003	-9999	0	-10000	0	0
mol:Sphinganine-1-P	-0.005	0.001	0	5	-10000	0	5
growth factor activity	0	0	-9999	0	-10000	0	0
S1P/S1P2/G12/G13	0.016	0.035	-9999	0	-0.13	4	4
GNAI3	0.01	0	-9999	0	-10000	0	0
G12/G13	0.015	0	-9999	0	-10000	0	0
S1PR3	0.01	0.002	-9999	0	-10000	0	0
S1PR2	0.01	0	-9999	0	-10000	0	0
EDG1	0	0	-9999	0	-10000	0	0
S1P1/S1P	-0.004	0.033	-9999	0	-0.15	4	4
S1PR5	0.009	0.003	-9999	0	-10000	0	0
S1PR4	0.009	0.004	-9999	0	-10000	0	0
GNAI1	0.01	0.002	-9999	0	-10000	0	0
S1P/S1P5/G12	0.008	0.036	-9999	0	-0.13	5	5
S1P/S1P3/Gq	0.005	0.039	-9999	0	-0.2	2	2
S1P/S1P4/Gi	0.001	0.033	-9999	0	-0.14	3	3
GNAQ	0.01	0	-9999	0	-10000	0	0
GNAZ	0.01	0.002	-9999	0	-10000	0	0
GNA14	0.009	0.003	-9999	0	-10000	0	0
GNA15	0.01	0.001	-9999	0	-10000	0	0
GNA12	0.01	0	-9999	0	-10000	0	0
GNA13	0.01	0	-9999	0	-10000	0	0
GNA11	0.01	0	-9999	0	-10000	0	0
ABCC1	0.01	0	-9999	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.013	0.023	-9999	-10000	0	0
CLOCK	0.01	0.003	-9999	-10000	0	0
TIMELESS/CRY2	0.009	0.014	-9999	-10000	0	0
DEC1/BMAL1	0.005	0.02	-9999	-0.12	2	2
ATR	0.01	0.002	-9999	-10000	0	0
NR1D1	0.002	0.012	-9999	-10000	0	0
ARNTL	0.01	0.002	-9999	-10000	0	0
TIMELESS	0.002	0.012	-9999	-10000	0	0
NPAS2	0.011	0	-9999	-10000	0	0
CRY2	0.01	0	-9999	-10000	0	0
mol:CO	-0.002	0	-9999	-10000	0	0
CHEK1	0.01	0	-9999	-10000	0	0
mol:HEME	0.002	0	-9999	-10000	0	0
PER1	0.01	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.013	0.041	-9999	-0.14	5	5
BMAL1/CLOCK	-0.009	0.083	-9999	-0.42	2	2
S phase of mitotic cell cycle	0.013	0.023	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.013	0.023	-9999	-10000	0	0
mol:NADPH	0.002	0	-9999	-10000	0	0
PER1/TIMELESS	0.009	0.014	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.002	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.013	0.053	0.48	1	-10000	0	1
regulation of axonogenesis	-0.006	0.017	-10000	0	-0.15	1	1
myoblast fusion	-0.009	0.032	-10000	0	-0.28	1	1
mol:GTP	0.011	0.018	0.17	1	-10000	0	1
regulation of calcium-dependent cell-cell adhesion	-0.02	0.028	0.096	1	-0.23	1	2
ARF1/GTP	0.015	0.002	-10000	0	-10000	0	0
mol:GM1	0.006	0.017	0.16	1	-10000	0	1
mol:Choline	-0.001	0.016	0.14	1	-10000	0	1
lamellipodium assembly	0.007	0.034	0.28	1	-10000	0	1
MAPK3	0.013	0.033	0.31	1	-10000	0	1
ARF6/GTP/NME1/Tiam1	0.021	0.028	0.24	1	-0.097	1	2
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0.009	0.032	0.28	1	-10000	0	1
ARF1/GDP	0.012	0.029	0.24	1	-10000	0	1
ARF6	0.014	0.011	0.11	1	-10000	0	1
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	0.01	0.004	0.037	1	-10000	0	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.033	0.31	1	-10000	0	1
actin filament bundle formation	-0.01	0.012	-10000	0	-10000	0	0
KALRN	0.004	0.009	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.015	0	-10000	0	-10000	0	0
RhoA/GDP	0.01	0.012	-10000	0	-10000	0	0
NME1	0.011	0.003	0.037	1	-10000	0	1
Rac1/GDP	0.01	0.012	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.011	0.018	0.17	1	-10000	0	1
cortical actin cytoskeleton organization	0.004	0.014	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	0.011	0.018	0.17	1	-10000	0	1
ARF6/GTP	0.011	0.018	0.17	1	-10000	0	1
RhoA/GTP	0.015	0.002	-10000	0	-10000	0	0
mol:GDP	0.009	0.035	0.32	1	-10000	0	1
ARF6/GTP/RAB11FIP3/RAB11A	0.023	0.014	0.15	1	-10000	0	1
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.009	0.017	0.16	1	-10000	0	1
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.007	0.034	0.28	1	-10000	0	1
ruffle organization	0.006	0.017	0.15	1	-10000	0	1
regulation of epithelial cell migration	0.011	0.018	0.17	1	-10000	0	1
PLD2	0.009	0.017	0.16	1	-10000	0	1
PIP5K1A	0.006	0.017	0.15	1	-10000	0	1
mol:Phosphatidic acid	-0.001	0.016	0.14	1	-10000	0	1
Rac1/GTP	0.004	0.014	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.006	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.016	0	-10000	0	-10000	0	0
CDKN1B	0.004	0.011	-10000	0	-10000	0	0
CDKN1A	0.002	0.016	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.01	0.001	-10000	0	-10000	0	0
FOXO3	0.004	0.011	-10000	0	-10000	0	0
AKT1	0.005	0.006	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
AKT3	0.005	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.004	0.011	-10000	0	-10000	0	0
AKT1/ASK1	0.001	0.029	-10000	0	-10000	0	0
BAD/YWHAZ	0.021	0	-10000	0	-10000	0	0
RICTOR	0.01	0.002	-10000	0	-10000	0	0
RAF1	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.001	0.028	-10000	0	-10000	0	0
TSC1	0.004	0.011	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
AKT1/RAF1	0.012	0.012	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.004	0.011	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.001	0.019	0.17	1	-10000	0	1
MAP3K5	0.009	0.004	-10000	0	-10000	0	0
MAPKAP1	0.01	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.002	0.033	0.17	1	-10000	0	1
YWHAH	0.01	0	-10000	0	-10000	0	0
AKT1S1	0.004	0.011	-10000	0	-10000	0	0
CASP9	0.004	0.011	-10000	0	-10000	0	0
YWHAB	0.01	0.001	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.01	0.011	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.021	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
SRC	0.01	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.002	0.024	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.005	0.005	-10000	0	-10000	0	0
CHUK	0.004	0.011	-10000	0	-10000	0	0
BAD/BCL-XL	0.014	0.012	-10000	0	-10000	0	0
mTORC2	0.009	0.019	-10000	0	-0.089	3	3
AKT2	0.005	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.003	0.036	-10000	0	-0.16	1	1
PDPK1	0.01	0	-10000	0	-10000	0	0
MDM2	0.004	0.011	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.011	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.016	0.012	-10000	0	-10000	0	0
TSC1/TSC2	0.002	0.011	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.011	-10000	0	-10000	0	0
glucose import	-0.001	0.017	0.15	1	-10000	0	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.004	0.01	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.001	0.017	0.15	1	-10000	0	1
GSK3A	0.004	0.011	-10000	0	-10000	0	0
FOXO1	0.004	0.011	-10000	0	-10000	0	0
GSK3B	0.004	0.011	-10000	0	-10000	0	0
SFN	0.007	0.005	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.002	0.011	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.007	0.029	-10000	0	-0.25	1	1
PRKACA	0.01	0	-10000	0	-10000	0	0
KPNA1	0.01	0	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
RHEB	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.021	0.021	-10000	0	-0.15	1	1
Ran/GTP/Exportin 1/HDAC1	-0.008	0.011	-10000	0	-0.075	2	2
NF kappa B1 p50/RelA/I kappa B alpha	0.017	0.03	-10000	0	-0.18	1	1
SUMO1	0.01	0	-10000	0	-10000	0	0
ZFPM1	0.01	0.001	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.004	0	-10000	0	-10000	0	0
FKBP3	0.01	0	-10000	0	-10000	0	0
Histones	0.026	0.018	-10000	0	-10000	0	0
YY1/LSF	0.007	0.032	-10000	0	-0.15	3	3
SMG5	0.01	0	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.006	0.016	-10000	0	-0.13	1	1
I kappa B alpha/HDAC1	0.015	0.019	-10000	0	-10000	0	0
SAP18	0.01	0	-10000	0	-10000	0	0
RELA	0.011	0.027	0.11	4	-0.14	1	5
HDAC1/Smad7	0.021	0	-10000	0	-10000	0	0
RANGAP1	0.01	0	-10000	0	-10000	0	0
HDAC3/TR2	0.015	0.019	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.01	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.016	0.024	-10000	0	-0.13	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.01	0.001	-10000	0	-10000	0	0
GATA1	0.003	0.005	-10000	0	-10000	0	0
Mad/Max	0.015	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.01	0.014	-10000	0	-10000	0	0
RBBP7	0.01	0	-10000	0	-10000	0	0
NPC	0.006	0	-10000	0	-10000	0	0
RBBP4	0.01	0	-10000	0	-10000	0	0
MAX	0.01	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
NFKBIA	0.006	0.012	-10000	0	-10000	0	0
KAT2B	0.01	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.004	0.026	-10000	0	-0.13	3	3
SIN3 complex	0.022	0.023	-10000	0	-0.093	3	3
SMURF1	0.01	0	-10000	0	-10000	0	0
CHD3	0.01	0	-10000	0	-10000	0	0
SAP30	0.01	0.002	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.01	0	-10000	0	-10000	0	0
YY1/HDAC3	0.004	0.028	-10000	0	-0.12	3	3
YY1/HDAC2	0.007	0.032	-10000	0	-0.15	3	3
YY1/HDAC1	0.007	0.032	-10000	0	-0.15	3	3
NuRD/MBD2 Complex (MeCP1)	0.01	0	-10000	0	-10000	0	0
PPARG	-0.029	0.086	0.12	3	-0.2	15	18
HDAC8/hEST1B	0.021	0	-10000	0	-10000	0	0
UBE2I	0.01	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.015	0.019	-10000	0	-10000	0	0
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.011	0	-10000	0	-10000	0	0
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.006	0.012	-10000	0	-10000	0	0
HDAC2	0.01	0	-10000	0	-10000	0	0
YY1	-0.001	0.034	-10000	0	-0.18	3	3
HDAC8	0.01	0	-10000	0	-10000	0	0
SMAD7	0.01	0	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
MXD1	0.01	0	-10000	0	-10000	0	0
STAT3	0.007	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.01	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.013	0.031	-10000	0	-0.14	3	3
YY1/SAP30/HDAC1	0.009	0.036	-10000	0	-0.14	3	3
EP300	0.01	0	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.007	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.012	-10000	0	-10000	0	0
histone deacetylation	0.01	0	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.009	0.01	-10000	0	-10000	0	0
nuclear export	-0.021	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GATAD2B	0.01	0	-10000	0	-10000	0	0
GATAD2A	0.01	0	-10000	0	-10000	0	0
GATA2/HDAC3	0.015	0.019	-10000	0	-10000	0	0
GATA1/HDAC1	0.01	0.004	-10000	0	-10000	0	0
GATA1/HDAC3	0.008	0.014	-10000	0	-10000	0	0
CHD4	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.01	0.016	-10000	0	-0.12	1	1
SIN3/HDAC complex/Mad/Max	0.005	0.024	-10000	0	-10000	0	0
NuRD Complex	0.012	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.025	0.017	-10000	0	-10000	0	0
SIN3B	0.01	0	-10000	0	-10000	0	0
MTA2	0.01	0	-10000	0	-10000	0	0
SIN3A	0.01	0	-10000	0	-10000	0	0
XPO1	0.01	0.002	-10000	0	-10000	0	0
SUMO1/HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC complex	0.027	0	-10000	0	-10000	0	0
GATA1/Fog1	0.009	0.015	-10000	0	-0.12	1	1
FKBP25/HDAC1/HDAC2	0.021	0	-10000	0	-10000	0	0
TNF	0.007	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	0.005	0.024	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.01	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.014	0.014	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.006	0.022	-10000	0	-0.19	1	1
SIN3/HDAC complex/NCoR1	0.004	0.024	-10000	0	-10000	0	0
TFCP2	0.01	0	-10000	0	-10000	0	0
NR2C1	0.01	0.002	-10000	0	-10000	0	0
MBD3	0.01	0	-10000	0	-10000	0	0
MBD2	0.01	0	-10000	0	-10000	0	0

×

TCGA08_p53

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.Total.Perturbations
CDKN2A	-0.003	0.001	-10000	0	-9999	0
TP53	0.005	0.018	0.16	1	-9999	1
Senescence	0.005	0.018	0.16	1	-9999	1
Apoptosis	0.005	0.018	0.16	1	-9999	1
Activated_Oncogenes	0	0	-10000	0	-9999	0
MDM2	-0.004	0.001	-10000	0	-9999	0
MDM4	0.01	0.001	-10000	0	-9999	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.003	0.036	-9999	-10000	0	0
Syndecan-3/Neurocan	0.009	0.004	-9999	-10000	0	0
POMC	0.005	0.005	-9999	-10000	0	0
EGFR	0.01	0.002	-9999	-10000	0	0
Syndecan-3/EGFR	0.01	0.002	-9999	-10000	0	0
AGRP	0.003	0.005	-9999	-10000	0	0
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.01	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.01	0	-9999	-10000	0	0
APH1A	0.01	0	-9999	-10000	0	0
NCAN	0.007	0.005	-9999	-10000	0	0
long-term memory	0.017	0	-9999	-10000	0	0
Syndecan-3/IL8	0.009	0.004	-9999	-10000	0	0
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0.015	0	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
limb bud formation	0.004	0	-9999	-10000	0	0
MC4R	0.003	0.005	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PTN	0.007	0.005	-9999	-10000	0	0
FGFR/FGF/Syndecan-3	0.004	0	-9999	-10000	0	0
neuron projection morphogenesis	0	0.047	-9999	-10000	0	0
Syndecan-3/AgRP	0.006	0.003	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.007	0.005	-9999	-10000	0	0
Fyn/Cortactin	0.015	0	-9999	-10000	0	0
SDC3	0.004	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.008	0.004	-9999	-10000	0	0
IL8	0.007	0.005	-9999	-10000	0	0
Syndecan-3/Fyn/Cortactin	0.017	0	-9999	-10000	0	0
Syndecan-3/CASK	0.004	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.035	0.061	-9999	-0.12	26	26
Gamma Secretase	0.031	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.011	0.022	-10000	0	-0.12	2	2
AKT1	-0.005	0.075	0.29	2	-0.25	2	4
PTK2B	0.001	0.054	0.23	2	-10000	0	2
VEGFR2 homodimer/Frs2	0.012	0.008	-10000	0	-10000	0	0
CAV1	0.01	0.001	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.014	0.022	-10000	0	-10000	0	0
endothelial cell proliferation	0.005	0.081	0.35	2	-0.22	1	3
mol:Ca2+	-0.005	0.05	0.24	2	-10000	0	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.014	0.032	-10000	0	-10000	0	0
RP11-342D11.1	-0.007	0.045	0.23	2	-10000	0	2
CDH5	0.01	0	-10000	0	-10000	0	0
VEGFA homodimer	0.021	0.024	-10000	0	-0.093	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	0.01	0	-10000	0	-10000	0	0
HRAS/GDP	0.011	0.032	-10000	0	-0.14	2	2
SH2D2A	0.01	0.002	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.003	0.047	-10000	0	-0.25	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.01	0.03	-10000	0	-10000	0	0
VEGFR1 homodimer	0.01	0.002	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.021	0.036	-10000	0	-0.15	2	2
GRB10	-0.006	0.056	0.24	2	-0.27	1	3
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PAK1	0.01	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.018	0.033	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.007	0.04	-10000	0	-0.19	1	1
HIF1A	0.01	0.001	-10000	0	-10000	0	0
FRS2	0.01	0	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.013	0.032	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.01	0	-10000	0	-10000	0	0
Nck/Pak	0.014	0.015	-10000	0	-0.12	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.014	0.022	-10000	0	-10000	0	0
mol:GDP	0.015	0.034	-10000	0	-0.15	2	2
mol:NADP	0.001	0.056	0.23	2	-0.26	1	3
eNOS/Hsp90	0.006	0.055	0.22	2	-0.25	1	3
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.005	0.05	0.24	2	-10000	0	2
HIF1A/ARNT	0.014	0.015	-10000	0	-0.12	1	1
SHB	0.01	0.002	-10000	0	-10000	0	0
VEGFA	0.009	0.007	-10000	0	-0.046	1	1
VEGFC	0.009	0.003	-10000	0	-10000	0	0
FAK1/Vinculin	0.013	0.056	0.22	2	-10000	0	2
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.015	0.028	-10000	0	-10000	0	0
PTPN6	0.009	0.003	-10000	0	-10000	0	0
EPAS1	0.013	0.007	-10000	0	-10000	0	0
mol:L-citrulline	0.001	0.056	0.23	2	-0.26	1	3
ITGAV	0.01	0.001	-10000	0	-10000	0	0
PIK3CA	0.01	0.002	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.02	0.022	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.013	0.033	-10000	0	-0.17	1	1
VEGFR2/3 heterodimer	0.012	0.008	-10000	0	-10000	0	0
VEGFB	0.01	0	-10000	0	-10000	0	0
MAPK11	-0.003	0.059	0.26	2	-10000	0	2
VEGFR2 homodimer	0.014	0.052	0.34	2	-10000	0	2
FLT1	0.01	0.002	-10000	0	-10000	0	0
NEDD4	0.009	0.006	-10000	0	-0.046	1	1
MAPK3	-0.002	0.06	0.29	2	-0.19	1	3
MAPK1	-0.002	0.06	0.29	2	-0.19	1	3
VEGFA145/NRP2	0.004	0.037	-10000	0	-0.12	6	6
VEGFR1/2 heterodimer	0.012	0.008	-10000	0	-10000	0	0
KDR	0.014	0.052	0.34	2	-10000	0	2
VEGFA165/NRP1/VEGFR2 homodimer	0.007	0.036	-10000	0	-0.15	1	1
SRC	0.01	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.002	0.061	0.29	2	-0.2	1	3
PI3K	-0.004	0.052	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.013	0.025	-10000	0	-10000	0	0
FES	-0.006	0.051	0.24	2	-10000	0	2
GAB1	-0.001	0.038	-10000	0	-0.2	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.014	0.022	-10000	0	-10000	0	0
CTNNB1	0.01	0.001	-10000	0	-10000	0	0
SOS1	0.01	0.001	-10000	0	-10000	0	0
ARNT	0.01	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.005	0.055	0.22	2	-0.25	1	3
VEGFR2 homodimer/VEGFA homodimer/Yes	0.014	0.022	-10000	0	-10000	0	0
PI3K/GAB1	0.002	0.073	0.28	2	-0.27	2	4
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.022	0.026	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.012	0.022	-10000	0	-10000	0	0
HSP90AA1	0.01	0	-10000	0	-10000	0	0
CDC42	-0.006	0.051	0.24	2	-10000	0	2
actin cytoskeleton reorganization	0.01	0.029	-10000	0	-10000	0	0
PTK2	0.008	0.058	0.22	2	-10000	0	2
EDG1	-0.007	0.045	0.23	2	-10000	0	2
mol:DAG	-0.005	0.05	0.24	2	-10000	0	2
CaM/Ca2+	-0.012	0.03	0.12	2	-0.14	1	3
MAP2K3	-0.009	0.041	0.23	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.012	0.041	-10000	0	-0.27	1	1
PLCG1	-0.006	0.051	0.24	2	-10000	0	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.016	0.028	-10000	0	-10000	0	0
IQGAP1	0.01	0.002	-10000	0	-10000	0	0
YES1	0.01	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.014	0.022	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.01	0.027	-10000	0	-10000	0	0
cell migration	0.003	0.064	0.2	2	-10000	0	2
mol:PI-3-4-5-P3	-0.003	0.049	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
VEGFB/NRP1	-0.014	0.022	-10000	0	-0.15	1	1
mol:NO	0.001	0.056	0.23	2	-0.26	1	3
PXN	0.01	0	-10000	0	-10000	0	0
HRAS/GTP	-0.018	0.024	-10000	0	-0.14	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.008	0.039	-10000	0	-0.27	1	1
VHL	0.01	0	-10000	0	-10000	0	0
ITGB3	0.01	0.002	-10000	0	-10000	0	0
NOS3	0	0.06	0.24	2	-0.28	1	3
VEGFR2 homodimer/VEGFA homodimer/Sck	0.014	0.022	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.006	0.049	0.23	2	-10000	0	2
PRKCB	-0.012	0.036	-10000	0	-0.22	1	1
VCL	0.01	0.001	-10000	0	-10000	0	0
VEGFA165/NRP1	0.003	0.023	-10000	0	-0.15	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	0.014	0.022	-10000	0	-10000	0	0
VEGFA165/NRP2	0.004	0.037	-10000	0	-0.12	6	6
MAPKKK cascade	-0.02	0.032	-10000	0	-0.24	1	1
NRP2	0.01	0.002	-10000	0	-10000	0	0
VEGFC homodimer	0.009	0.003	-10000	0	-10000	0	0
NCK1	0.01	0.001	-10000	0	-10000	0	0
ROCK1	0.01	0	-10000	0	-10000	0	0
FAK1/Paxillin	0.013	0.056	0.22	2	-10000	0	2
MAP3K13	-0.008	0.043	0.24	1	-10000	0	1
PDPK1	-0.009	0.064	0.29	2	-10000	0	2

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.008	0.01	-9999	-0.072	2	2
MDM2/SUMO1	0.016	0	-9999	-10000	0	0
HDAC4	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.008	0.01	-9999	-0.072	2	2
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.004	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.002	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0.016	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.027	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.004	0	-9999	-10000	0	0
Ran/GTP	0.01	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.01	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.007	0.013	-9999	-10000	0	0
NPC	0.006	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf6 trafficking 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.01	0.002	-9999	-10000	0	0
CLTC	0.007	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.004	0	-9999	-10000	0	0
Dynamin 2/GTP	0.009	0	-9999	-10000	0	0
EXOC4	0.01	0	-9999	-10000	0	0
CD59	0.004	0	-9999	-10000	0	0
CPE	-0.004	0.001	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
membrane fusion	0.004	0	-9999	-10000	0	0
CTNND1	-0.007	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.004	0	-9999	-10000	0	0
TSHR	-0.003	0.001	-9999	-10000	0	0
INS	0.003	0.012	-9999	-10000	0	0
BIN1	0.01	0	-9999	-10000	0	0
mol:Choline	0.004	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	-0.004	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.009	0	-9999	-10000	0	0
JUP	0.005	0.01	-9999	-10000	0	0
ASAP2/amphiphysin II	0.02	0	-9999	-10000	0	0
ARF6/GTP	0.008	0	-9999	-10000	0	0
CDH1	-0.008	0.036	-9999	-10000	0	0
clathrin-independent pinocytosis	0.008	0	-9999	-10000	0	0
MAPK8IP3	0.01	0	-9999	-10000	0	0
positive regulation of endocytosis	0.008	0	-9999	-10000	0	0
EXOC2	0.01	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	-0.001	0.041	-9999	-0.16	5	5
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.005	0.03	-9999	-10000	0	0
positive regulation of phagocytosis	-0.004	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0.014	0	-9999	-10000	0	0
ACAP1	0.002	0.02	-9999	-0.12	2	2
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.006	0.013	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.004	0.005	-9999	-10000	0	0
JIP4/KLC1	0.02	0	-9999	-10000	0	0
EXOC1	0.01	0	-9999	-10000	0	0
exocyst	-0.001	0.041	-9999	-0.16	5	5
RALA/GTP	0.008	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.014	0	-9999	-10000	0	0
receptor recycling	0.008	0	-9999	-10000	0	0
CTNNA1	-0.007	0	-9999	-10000	0	0
NME1	-0.004	0	-9999	-10000	0	0
clathrin coat assembly	0.007	0	-9999	-10000	0	0
IL2RA	0.006	0.039	-9999	-10000	0	0
VAMP3	-0.004	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.011	0.013	-9999	-10000	0	0
EXOC6	0.01	0.002	-9999	-10000	0	0
PLD1	0.004	0	-9999	-10000	0	0
PLD2	0.004	0	-9999	-10000	0	0
EXOC5	0.01	0.001	-9999	-10000	0	0
PIP5K1C	0.004	0	-9999	-10000	0	0
SDC1	0.004	0	-9999	-10000	0	0
ARF6/GDP	0.009	0	-9999	-10000	0	0
EXOC7	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin	0.005	0.031	-9999	-10000	0	0
mol:Phosphatidic acid	0.004	0	-9999	-10000	0	0
endocytosis	-0.019	0	-9999	-10000	0	0
SCAMP2	0.01	0	-9999	-10000	0	0
ADRB2	0.005	0.001	-9999	-10000	0	0
EXOC3	0.01	0	-9999	-10000	0	0
ASAP2	0.01	0	-9999	-10000	0	0
Dynamin 2/GDP	0.011	0	-9999	-10000	0	0
KLC1	0.01	0	-9999	-10000	0	0
AVPR2	0.014	0.035	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.002	0.029	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.008	0.005	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.01	0	-9999	-10000	0	0
HIF1A/p53	0.005	0.017	-9999	-0.12	1	1
HIF1A	-0.002	0.016	-9999	-0.13	1	1
COPS5	0.01	0.001	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.026	0.023	-9999	-0.088	3	3
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	0.01	0.002	-9999	-10000	0	0
ARNT/IPAS	-0.006	0.047	-9999	-0.12	11	11
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.005	0.017	-9999	-0.12	1	1
CUL2	0.01	0.002	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.021	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.005	0.017	-9999	-0.12	1	1
PHD1-3/OS9	0.021	0.026	-9999	-0.093	4	4
HIF1A/RACK1/Elongin B/Elongin C	0.014	0.019	-9999	-0.12	1	1
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.005	0.017	-9999	-0.12	1	1
EGLN3	0.01	0.002	-9999	-10000	0	0
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.012	0.018	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	0.004	0.017	-9999	-0.12	1	1

×

PDGFR-beta signaling pathway

Figure S122. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S122. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0	0.042	-9999	-0.17	1	1
PDGFB-D/PDGFRB/SLAP	0.008	0.027	-9999	-0.13	3	3
PDGFB-D/PDGFRB/APS/CBL	0.021	0.001	-9999	-10000	0	0
AKT1	-0.016	0.016	-9999	-0.14	1	1
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.004	0.04	-9999	-0.17	1	1
PIK3CA	0.01	0.002	-9999	-10000	0	0
FGR	-0.027	0.1	-9999	-0.42	5	5
mol:Ca2+	0	0.038	-9999	-10000	0	0
MYC	0.004	0.05	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.001	0.017	-9999	-0.083	2	2
LRP1/PDGFRB/PDGFB	0.018	0.02	-9999	-0.1	2	2
GRB10	0.01	0.001	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0.038	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.007	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.013	0.016	-9999	-0.13	1	1
cell cycle arrest	0.008	0.027	-9999	-0.13	3	3
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	-0.016	0.015	-9999	-0.13	1	1
GAB1	0.001	0.058	-9999	-0.2	2	2
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0	0.055	-9999	-0.18	2	2
PDGFB-D/PDGFRB	0.018	0.015	-9999	-0.1	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.015	0.001	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.011	0.04	-9999	-0.21	1	1
positive regulation of MAPKKK cascade	0.015	0.003	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0	0.038	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.011	0.006	-9999	-10000	0	0
SHB	0.01	0.002	-9999	-10000	0	0
BLK	-0.045	0.14	-9999	-0.42	9	9
PTPN2	0.01	0.003	-9999	-0.009	2	2
PDGFB-D/PDGFRB/SNX15	0.015	0.001	-9999	-10000	0	0
BCAR1	0.01	0	-9999	-10000	0	0
VAV2	0.002	0.061	-9999	-0.21	1	1
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.015	0.001	-9999	-10000	0	0
LCK	-0.073	0.16	-9999	-0.41	14	14
PDGFRB	0.009	0.005	-9999	-0.009	5	5
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.006	0.049	-9999	-0.41	1	1
ABL1	-0.006	0.058	-9999	-0.18	2	2
PDGFB-D/PDGFRB/CBL	0.002	0.058	-9999	-0.2	1	1
PTPN1	0.01	0.004	-9999	-0.009	3	3
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.009	0.003	-9999	-10000	0	0
cell proliferation	0.005	0.048	-9999	-10000	0	0
SLA	0.009	0.004	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.014	0.02	-9999	-10000	0	0
SRC	-0.002	0.016	-9999	-10000	0	0
PI3K	-0.015	0.018	-9999	-0.12	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.017	0.007	-9999	-10000	0	0
SH2B2	0.01	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.004	0.041	-9999	-0.17	1	1
LYN	-0.001	0.016	-9999	-10000	0	0
LRP1	0.01	0.001	-9999	-10000	0	0
SOS1	0.01	0.001	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.01	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0.028	0.018	-9999	-0.085	2	2
SPHK1	0.01	0.003	-9999	-10000	0	0
EDG1	0	0.001	-9999	-10000	0	0
mol:DAG	0	0.038	-9999	-10000	0	0
PLCG1	0	0.039	-9999	-10000	0	0
NHERF/PDGFRB	0.021	0.001	-9999	-10000	0	0
YES1	0	0.016	-9999	-10000	0	0
cell migration	0.021	0.001	-9999	-10000	0	0
SHC/Grb2/SOS1	0.028	0.018	-9999	-0.086	2	2
SLC9A3R2	0.01	0	-9999	-10000	0	0
SLC9A3R1	0.01	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.026	0.001	-9999	-10000	0	0
FYN	-0.001	0.016	-9999	-10000	0	0
DOK1	-0.007	0.011	-9999	-0.095	1	1
HRAS/GTP	0.008	0	-9999	-10000	0	0
PDGFB	0.01	0.002	-9999	-10000	0	0
RAC1	0.002	0.058	-9999	-10000	0	0
PRKCD	-0.007	0.012	-9999	-0.094	1	1
FER	-0.006	0.012	-9999	-0.094	1	1
MAPKKK cascade	-0.012	0.012	-9999	-10000	0	0
RASA1	-0.007	0.012	-9999	-0.094	1	1
NCK1	0.01	0.001	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.008	0.012	-9999	-0.09	1	1
PDGFB-D/PDGFRB/SHB	0.01	0.027	-9999	-0.13	3	3
chemotaxis	-0.006	0.057	-9999	-0.18	2	2
STAT1-3-5/STAT1-3-5	0.02	0.014	-9999	-0.084	1	1
Bovine Papilomavirus E5/PDGFRB	0.007	0.005	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	-0.008	0.004	-9999	-9999
PI3K Class IB/PDE3B	0.008	0.004	-9999	-9999
PDE3B	0.008	0.004	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.001	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.004	0.01	-9999	-10000	0	0
AP2	0.015	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.015	0	-9999	-10000	0	0
CLTB	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.006	0	-9999	-10000	0	0
CD4	0.01	0.002	-9999	-10000	0	0
CLTA	0.01	0	-9999	-10000	0	0
mol:GTP	-0.001	0	-9999	-10000	0	0
ARFGAP1	-0.003	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.002	0	-9999	-10000	0	0
ARF1/GTP	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.002	0	-9999	-10000	0	0
mol:Choline	0.001	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0.001	0	-9999	-10000	0	0
ARF1/GDP	0.002	0	-9999	-10000	0	0
AP2M1	0.01	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	-0.005	0	-9999	-10000	0	0
Rac/GTP	0.008	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.015	0	-9999	-10000	0	0
ARFIP2	0.01	0	-9999	-10000	0	0
COPA	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.004	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.007	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.01	0	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.005	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.01	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.014	0	-9999	-10000	0	0
CYTH2	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.014	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.002	0.026	-9999	-0.13	3	3
PLD2	0.001	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	-0.003	0	-9999	-10000	0	0
PIP5K1A	0.002	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.007	0.008	-9999	-0.06	1	1
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0.001	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.003	0	-9999	-10000	0	0
GOSR2	0.004	0	-9999	-10000	0	0
USO1	0	0.039	-9999	-0.35	1	1
GBF1	0.004	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.015	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.016	0.023	-9999	-0.1	3	3

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.015	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0.031	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0.015	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0.014	-9999	-9999
regulation of B cell activation	0.014	-9999	-9999

pid_entity	TCGA.YZ.A985	TCGA.YZ.A984	TCGA.YZ.A983	TCGA.YZ.A982
109_MAP3K5	0.0068	0	0.13	0
47_PPARGC1A	-9.6e-17	0.01	0	0.01
105_BMP4	0.01	0.01	0.01	0.01
105_BMP6	0.01	0.01	0.01	0.01
105_BMP7	0.01	0	0.01	0.01
105_BMP2	0.01	0.01	0.01	0.01
131_RELN/VLDLR	0.026	0.026	-0.093	0.026
30_TGFB1/TGF beta receptor Type II	0.01	0.01	0.01	0.01
101_Ephrin B1/EPHB1-2/NCK2	0.049	0	0.02	0.023
103_RAP1A	0.01	0.01	0.01	0.01