GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in SARC-TP

Sarcoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in SARC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1FJ2G79

Overview

Introduction

This pipeline performs Gene Set Enrichment Analysis (GSEA) using The Broad Institute GSEA tool with MSigDB - Class2: Canonical Pathways gene sets. For a given phenotype subtype, it shows what pathways are significantly enriched in each subtype by comparing gene expression profiles between subtypes. Here, the phenotype is mRNAseq_cNMF subtypes having more than three samples and the input expression file "SARC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run. This pipeline has the following features:

For each subtype, calculates enrichment scores (ES) using signal to noise (S2N) that checks similarity between subtypes in expression level then calculates p values through permutation test.
Lists pathways significantly enriched in each phenotype subtype and their enrichment scores (ES).
Lists top 20 core genes enriched in each significant gene set and their enrichment scores (ES).
Checks if the top core genes are up-regulated or down-regulated.
Checks if the top core genes are high expressed or low expressed.
Checks if the top core genes are significantly differently expressed genes.

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 714
Number of samples: 259
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 116
pheno.type: 2 - 3 :[ clus2 ] 78
pheno.type: 3 - 3 :[ clus3 ] 65

For the expression subtypes of 18187 genes in 260 samples, GSEA found enriched gene sets in each cluster using 259 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG RNA POLYMERASE, KEGG PROTEASOME, KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION, KEGG CHEMOKINE SIGNALING PATHWAY, KEGG LYSOSOME, KEGG APOPTOSIS, KEGG COMPLEMENT AND COAGULATION CASCADES, KEGG ANTIGEN PROCESSING AND PRESENTATION, KEGG TOLL LIKE RECEPTOR SIGNALING PATHWAY

And common core enriched genes are PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMA8, PSMB1, PSMB10

clus2

Top enriched gene sets are KEGG LYSINE DEGRADATION, KEGG PROPANOATE METABOLISM, KEGG BUTANOATE METABOLISM, KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, KEGG INSULIN SIGNALING PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA INTEGRIN PATHWAY, BIOCARTA MYOSIN PATHWAY, BIOCARTA RHO PATHWAY, SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES

And common core enriched genes are SRC, PPP1R12B, ROCK1, TLN1, VCL, ACAT1, ACAT2, ALDH1B1, ALDH2, ALDH3A2

clus3

Top enriched gene sets are KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE, KEGG WNT SIGNALING PATHWAY, KEGG AXON GUIDANCE, KEGG BASAL CELL CARCINOMA, BIOCARTA WNT PATHWAY, WNT SIGNALING, ST WNT BETA CATENIN PATHWAY, PID NOTCH PATHWAY, PID PS1PATHWAY, PID WNT SIGNALING PATHWAY

And common core enriched genes are WIF1, CCND1, FZD1, NKD1, DKK2, LRP6, TLE1, BTRC, LEF1, CXXC4

Results

Subtype clus1 enriched pathways

Table 3. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus1. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.59	1.9	0.002	0.28	0.35	0.37	0.15	0.32	0	0.063
KEGG RNA POLYMERASE	29	genes.ES.table	0.43	1.4	0.12	0.25	1	0.48	0.32	0.33	0.19	0.003
KEGG PROTEASOME	44	genes.ES.table	0.62	1.8	0.014	0.2	0.52	0.7	0.3	0.5	0.067	0.047
KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION	237	genes.ES.table	0.64	1.6	0.0058	0.14	0.92	0.55	0.14	0.48	0.076	0.005
KEGG CHEMOKINE SIGNALING PATHWAY	185	genes.ES.table	0.55	1.6	0.036	0.16	0.96	0.4	0.14	0.35	0.1	0.003
KEGG LYSOSOME	120	genes.ES.table	0.52	1.9	0.002	0.3	0.41	0.52	0.21	0.41	0	0.06
KEGG APOPTOSIS	86	genes.ES.table	0.46	1.6	0.042	0.15	0.94	0.38	0.22	0.3	0.086	0.005
KEGG COMPLEMENT AND COAGULATION CASCADES	62	genes.ES.table	0.7	1.6	0.018	0.15	0.95	0.5	0.098	0.45	0.089	0.004
KEGG ANTIGEN PROCESSING AND PRESENTATION	67	genes.ES.table	0.75	1.7	0.0058	0.12	0.77	0.67	0.15	0.57	0.054	0.013
KEGG TOLL LIKE RECEPTOR SIGNALING PATHWAY	89	genes.ES.table	0.66	1.8	0.0019	0.14	0.6	0.35	0.077	0.32	0.049	0.03

genes ES table in pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

Table S1. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CARD11	CARD11	CARD11	646	0.43	0.015	YES
2	RASGRP1	RASGRP1	RASGRP1	741	0.4	0.057	YES
3	NFKBIE	NFKBIE	NFKBIE	1006	0.34	0.083	YES
4	PSMB9	PSMB9	PSMB9	1057	0.33	0.12	YES
5	PSMB10	PSMB10	PSMB10	1128	0.32	0.15	YES
6	PRKCB	PRKCB	PRKCB	1564	0.26	0.16	YES
7	RASGRP3	RASGRP3	RASGRP3	1860	0.22	0.17	YES
8	PSMB8	PSMB8	PSMB8	2232	0.19	0.17	YES
9	PSMA8	PSMA8	PSMA8	2349	0.18	0.18	YES
10	BCL10	BCL10	BCL10	2575	0.16	0.19	YES
11	PSME2	PSME2	PSME2	2662	0.16	0.21	YES
12	NFKBIB	NFKBIB	NFKBIB	3084	0.14	0.2	YES
13	IKBKG	IKBKG	IKBKG	3119	0.13	0.21	YES
14	PSMC1	PSMC1	PSMC1	3141	0.13	0.23	YES
15	PSMB6	PSMB6	PSMB6	3312	0.12	0.23	YES
16	NRAS	NRAS	NRAS	3361	0.12	0.24	YES
17	NFKBIA	NFKBIA	NFKBIA	3457	0.12	0.25	YES
18	PSMD13	PSMD13	PSMD13	3578	0.11	0.26	YES
19	PSMB7	PSMB7	PSMB7	3761	0.11	0.26	YES
20	AKT1S1	AKT1S1	AKT1S1	3817	0.1	0.27	YES
21	PSMB3	PSMB3	PSMB3	3831	0.1	0.28	YES
22	MDM2	MDM2	MDM2	3832	0.1	0.3	YES
23	PSMA6	PSMA6	PSMA6	3864	0.1	0.31	YES
24	PSMA7	PSMA7	PSMA7	3902	0.1	0.32	YES
25	PSME1	PSME1	PSME1	3964	0.1	0.32	YES
26	THEM4	THEM4	THEM4	4039	0.098	0.33	YES
27	PSMA5	PSMA5	PSMA5	4193	0.093	0.34	YES
28	PSMA2	PSMA2	PSMA2	4238	0.092	0.34	YES
29	PSMB2	PSMB2	PSMB2	4344	0.088	0.35	YES
30	PSMD14	PSMD14	PSMD14	4517	0.082	0.35	YES
31	CASP9	CASP9	CASP9	4518	0.082	0.36	YES
32	PSMA1	PSMA1	PSMA1	4550	0.081	0.37	YES
33	PSMC4	PSMC4	PSMC4	4588	0.08	0.37	YES
34	UBA52	UBA52	UBA52	4613	0.079	0.38	YES
35	PSMC2	PSMC2	PSMC2	4628	0.079	0.39	YES
36	PSMA3	PSMA3	PSMA3	4730	0.076	0.39	YES
37	PSMB1	PSMB1	PSMB1	4783	0.075	0.4	YES
38	PSMD7	PSMD7	PSMD7	4966	0.07	0.4	YES
39	TRIB3	TRIB3	TRIB3	4992	0.07	0.4	YES
40	PSMC3	PSMC3	PSMC3	5066	0.068	0.41	YES
41	PSMC5	PSMC5	PSMC5	5078	0.067	0.42	YES
42	PSMA4	PSMA4	PSMA4	5165	0.065	0.42	YES
43	PSMD9	PSMD9	PSMD9	5262	0.062	0.42	YES
44	RPS6KB2	RPS6KB2	RPS6KB2	5314	0.061	0.42	YES
45	PSMD8	PSMD8	PSMD8	5360	0.06	0.43	YES
46	PSMD12	PSMD12	PSMD12	5434	0.058	0.43	YES
47	HRAS	HRAS	HRAS	5460	0.058	0.44	YES
48	PSMD3	PSMD3	PSMD3	5875	0.047	0.42	NO
49	PSMD4	PSMD4	PSMD4	5948	0.046	0.42	NO
50	MLST8	MLST8	MLST8	6017	0.044	0.42	NO
51	PSMB5	PSMB5	PSMB5	6231	0.039	0.42	NO
52	PSMB4	PSMB4	PSMB4	6434	0.035	0.41	NO
53	RPS27A	RPS27A	RPS27A	6457	0.035	0.41	NO
54	PSMD2	PSMD2	PSMD2	6470	0.034	0.42	NO
55	PTEN	PTEN	PTEN	6505	0.034	0.42	NO
56	CHUK	CHUK	CHUK	6563	0.032	0.42	NO
57	BTRC	BTRC	BTRC	6714	0.029	0.41	NO
58	BAD	BAD	BAD	6940	0.024	0.4	NO
59	PSMD11	PSMD11	PSMD11	7009	0.022	0.4	NO
60	PSMD1	PSMD1	PSMD1	7278	0.017	0.39	NO
61	KRAS	KRAS	KRAS	7309	0.016	0.39	NO
62	PSMD5	PSMD5	PSMD5	7634	0.0097	0.37	NO
63	RELA	RELA	RELA	7636	0.0097	0.38	NO
64	PSMF1	PSMF1	PSMF1	7810	0.0055	0.37	NO
65	MAPKAP1	MAPKAP1	MAPKAP1	7859	0.0043	0.36	NO
66	PSMD6	PSMD6	PSMD6	7915	0.0031	0.36	NO
67	PSMC6	PSMC6	PSMC6	7969	0.0021	0.36	NO
68	GSK3A	GSK3A	GSK3A	8246	-0.0034	0.34	NO
69	MTOR	MTOR	MTOR	8318	-0.005	0.34	NO
70	PHLPP1	PHLPP1	PHLPP1	8555	-0.01	0.33	NO
71	MALT1	MALT1	MALT1	8610	-0.011	0.33	NO
72	AKT1	AKT1	AKT1	8693	-0.013	0.32	NO
73	AKT2	AKT2	AKT2	8801	-0.016	0.32	NO
74	PSME4	PSME4	PSME4	9281	-0.026	0.3	NO
75	IKBKB	IKBKB	IKBKB	9634	-0.033	0.28	NO
76	FOXO4	FOXO4	FOXO4	9687	-0.034	0.28	NO
77	CDKN1A	CDKN1A	CDKN1A	9920	-0.038	0.27	NO
78	FOXO3	FOXO3	FOXO3	9996	-0.04	0.27	NO
79	MAP3K7	MAP3K7	MAP3K7	10070	-0.042	0.28	NO
80	PSMD10	PSMD10	PSMD10	10088	-0.042	0.28	NO
81	SKP1	SKP1	SKP1	10134	-0.043	0.28	NO
82	CREB1	CREB1	CREB1	10640	-0.053	0.26	NO
83	CUL1	CUL1	CUL1	11500	-0.073	0.22	NO
84	TSC2	TSC2	TSC2	11623	-0.076	0.22	NO
85	FBXW11	FBXW11	FBXW11	11763	-0.08	0.22	NO
86	REL	REL	REL	12049	-0.087	0.22	NO
87	FOXO1	FOXO1	FOXO1	12071	-0.088	0.23	NO
88	RICTOR	RICTOR	RICTOR	12945	-0.12	0.19	NO
89	PDPK1	PDPK1	PDPK1	13572	-0.14	0.18	NO
90	CDKN1B	CDKN1B	CDKN1B	13945	-0.15	0.17	NO
91	NR4A1	NR4A1	NR4A1	15019	-0.2	0.14	NO
92	AKT3	AKT3	AKT3	16353	-0.3	0.1	NO

Figure S1. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG RNA POLYMERASE

Table S2. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PSMB9	PSMB9	PSMB9	1057	0.33	0.013	YES
2	PSMB10	PSMB10	PSMB10	1128	0.32	0.077	YES
3	UNC5B	UNC5B	UNC5B	1949	0.21	0.078	YES
4	PSMB8	PSMB8	PSMB8	2232	0.19	0.1	YES
5	PSMA8	PSMA8	PSMA8	2349	0.18	0.14	YES
6	DAPK2	DAPK2	DAPK2	2442	0.17	0.17	YES
7	PSME2	PSME2	PSME2	2662	0.16	0.19	YES
8	PSMC1	PSMC1	PSMC1	3141	0.13	0.19	YES
9	PSMB6	PSMB6	PSMB6	3312	0.12	0.21	YES
10	PSMD13	PSMD13	PSMD13	3578	0.11	0.22	YES
11	PSMB7	PSMB7	PSMB7	3761	0.11	0.23	YES
12	PSMB3	PSMB3	PSMB3	3831	0.1	0.25	YES
13	PSMA6	PSMA6	PSMA6	3864	0.1	0.27	YES
14	PSMA7	PSMA7	PSMA7	3902	0.1	0.29	YES
15	PSME1	PSME1	PSME1	3964	0.1	0.31	YES
16	PSMA5	PSMA5	PSMA5	4193	0.093	0.32	YES
17	PSMA2	PSMA2	PSMA2	4238	0.092	0.34	YES
18	PSMB2	PSMB2	PSMB2	4344	0.088	0.35	YES
19	PSMD14	PSMD14	PSMD14	4517	0.082	0.36	YES
20	CASP9	CASP9	CASP9	4518	0.082	0.38	YES
21	PSMA1	PSMA1	PSMA1	4550	0.081	0.39	YES
22	PSMC4	PSMC4	PSMC4	4588	0.08	0.41	YES
23	UBA52	UBA52	UBA52	4613	0.079	0.42	YES
24	PSMC2	PSMC2	PSMC2	4628	0.079	0.44	YES
25	PSMA3	PSMA3	PSMA3	4730	0.076	0.45	YES
26	DAPK1	DAPK1	DAPK1	4732	0.076	0.47	YES
27	PSMB1	PSMB1	PSMB1	4783	0.075	0.48	YES
28	CASP3	CASP3	CASP3	4810	0.074	0.5	YES
29	PSMD7	PSMD7	PSMD7	4966	0.07	0.5	YES
30	PSMC3	PSMC3	PSMC3	5066	0.068	0.51	YES
31	PSMC5	PSMC5	PSMC5	5078	0.067	0.52	YES
32	PSMA4	PSMA4	PSMA4	5165	0.065	0.53	YES
33	PSMD9	PSMD9	PSMD9	5262	0.062	0.54	YES
34	PSMD8	PSMD8	PSMD8	5360	0.06	0.55	YES
35	PSMD12	PSMD12	PSMD12	5434	0.058	0.56	YES
36	PAK2	PAK2	PAK2	5806	0.049	0.55	YES
37	PSMD3	PSMD3	PSMD3	5875	0.047	0.56	YES
38	PSMD4	PSMD4	PSMD4	5948	0.046	0.56	YES
39	PSMB5	PSMB5	PSMB5	6231	0.039	0.55	YES
40	PSMB4	PSMB4	PSMB4	6434	0.035	0.55	YES
41	RPS27A	RPS27A	RPS27A	6457	0.035	0.56	YES
42	PSMD2	PSMD2	PSMD2	6470	0.034	0.56	YES
43	UNC5A	UNC5A	UNC5A	6864	0.026	0.55	NO
44	PSMD11	PSMD11	PSMD11	7009	0.022	0.54	NO
45	PSMD1	PSMD1	PSMD1	7278	0.017	0.53	NO
46	MAGED1	MAGED1	MAGED1	7481	0.013	0.52	NO
47	PSMD5	PSMD5	PSMD5	7634	0.0097	0.52	NO
48	PSMF1	PSMF1	PSMF1	7810	0.0055	0.51	NO
49	PSMD6	PSMD6	PSMD6	7915	0.0031	0.5	NO
50	PSMC6	PSMC6	PSMC6	7969	0.0021	0.5	NO
51	ARHGAP10	ARHGAP10	ARHGAP10	8048	0.00064	0.5	NO
52	DAPK3	DAPK3	DAPK3	8385	-0.0064	0.48	NO
53	PSME4	PSME4	PSME4	9281	-0.026	0.44	NO
54	PSMD10	PSMD10	PSMD10	10088	-0.042	0.4	NO
55	APPL1	APPL1	APPL1	10160	-0.043	0.41	NO
56	DCC	DCC	DCC	14135	-0.16	0.22	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RNA POLYMERASE.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RNA POLYMERASE, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PROTEASOME

Table S3. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	VAV1	VAV1	VAV1	42	0.76	0.046	YES
2	BTK	BTK	BTK	150	0.63	0.079	YES
3	PIK3AP1	PIK3AP1	PIK3AP1	174	0.61	0.12	YES
4	SYK	SYK	SYK	323	0.54	0.14	YES
5	CARD11	CARD11	CARD11	646	0.43	0.15	YES
6	BLK	BLK	BLK	710	0.41	0.17	YES
7	PIK3CD	PIK3CD	PIK3CD	717	0.41	0.2	YES
8	RASGRP1	RASGRP1	RASGRP1	741	0.4	0.22	YES
9	CD19	CD19	CD19	815	0.38	0.24	YES
10	LYN	LYN	LYN	877	0.36	0.26	YES
11	NFKBIE	NFKBIE	NFKBIE	1006	0.34	0.28	YES
12	PSMB9	PSMB9	PSMB9	1057	0.33	0.3	YES
13	CD79A	CD79A	CD79A	1100	0.32	0.31	YES
14	PSMB10	PSMB10	PSMB10	1128	0.32	0.33	YES
15	SH3KBP1	SH3KBP1	SH3KBP1	1164	0.31	0.35	YES
16	FYN	FYN	FYN	1290	0.29	0.36	YES
17	CD79B	CD79B	CD79B	1320	0.29	0.38	YES
18	PLCG2	PLCG2	PLCG2	1455	0.27	0.39	YES
19	BLNK	BLNK	BLNK	1522	0.26	0.4	YES
20	ORAI1	ORAI1	ORAI1	1557	0.26	0.41	YES
21	PRKCB	PRKCB	PRKCB	1564	0.26	0.43	YES
22	RASGRP3	RASGRP3	RASGRP3	1860	0.22	0.43	YES
23	PSMB8	PSMB8	PSMB8	2232	0.19	0.42	YES
24	ITPR2	ITPR2	ITPR2	2235	0.19	0.43	YES
25	PSMA8	PSMA8	PSMA8	2349	0.18	0.44	YES
26	BCL10	BCL10	BCL10	2575	0.16	0.43	YES
27	CBLB	CBLB	CBLB	2579	0.16	0.44	YES
28	ITPR3	ITPR3	ITPR3	2626	0.16	0.45	YES
29	PSME2	PSME2	PSME2	2662	0.16	0.46	YES
30	NFKBIB	NFKBIB	NFKBIB	3084	0.14	0.44	YES
31	IKBKG	IKBKG	IKBKG	3119	0.13	0.45	YES
32	PSMC1	PSMC1	PSMC1	3141	0.13	0.46	YES
33	PSMB6	PSMB6	PSMB6	3312	0.12	0.46	YES
34	NRAS	NRAS	NRAS	3361	0.12	0.46	YES
35	NFKBIA	NFKBIA	NFKBIA	3457	0.12	0.46	YES
36	PSMD13	PSMD13	PSMD13	3578	0.11	0.46	YES
37	PSMB7	PSMB7	PSMB7	3761	0.11	0.46	YES
38	AKT1S1	AKT1S1	AKT1S1	3817	0.1	0.46	YES
39	PSMB3	PSMB3	PSMB3	3831	0.1	0.47	YES
40	MDM2	MDM2	MDM2	3832	0.1	0.48	YES
41	PSMA6	PSMA6	PSMA6	3864	0.1	0.48	YES
42	PSMA7	PSMA7	PSMA7	3902	0.1	0.49	YES
43	PSME1	PSME1	PSME1	3964	0.1	0.49	YES
44	THEM4	THEM4	THEM4	4039	0.098	0.49	YES
45	PSMA5	PSMA5	PSMA5	4193	0.093	0.49	YES
46	GRB2	GRB2	GRB2	4194	0.093	0.49	YES
47	PSMA2	PSMA2	PSMA2	4238	0.092	0.5	YES
48	PSMB2	PSMB2	PSMB2	4344	0.088	0.5	YES
49	PSMD14	PSMD14	PSMD14	4517	0.082	0.49	YES
50	CASP9	CASP9	CASP9	4518	0.082	0.5	YES
51	PSMA1	PSMA1	PSMA1	4550	0.081	0.5	YES
52	PSMC4	PSMC4	PSMC4	4588	0.08	0.5	YES
53	UBA52	UBA52	UBA52	4613	0.079	0.51	YES
54	PSMC2	PSMC2	PSMC2	4628	0.079	0.51	YES
55	PSMA3	PSMA3	PSMA3	4730	0.076	0.51	YES
56	PSMB1	PSMB1	PSMB1	4783	0.075	0.51	YES
57	PSMD7	PSMD7	PSMD7	4966	0.07	0.51	YES
58	TRIB3	TRIB3	TRIB3	4992	0.07	0.51	YES
59	PSMC3	PSMC3	PSMC3	5066	0.068	0.51	YES
60	PSMC5	PSMC5	PSMC5	5078	0.067	0.52	YES
61	PSMA4	PSMA4	PSMA4	5165	0.065	0.51	YES
62	PSMD9	PSMD9	PSMD9	5262	0.062	0.51	YES
63	RPS6KB2	RPS6KB2	RPS6KB2	5314	0.061	0.51	YES
64	PSMD8	PSMD8	PSMD8	5360	0.06	0.52	YES
65	PSMD12	PSMD12	PSMD12	5434	0.058	0.52	YES
66	HRAS	HRAS	HRAS	5460	0.058	0.52	YES
67	PSMD3	PSMD3	PSMD3	5875	0.047	0.5	NO
68	PSMD4	PSMD4	PSMD4	5948	0.046	0.5	NO
69	MLST8	MLST8	MLST8	6017	0.044	0.5	NO
70	PSMB5	PSMB5	PSMB5	6231	0.039	0.49	NO
71	PSMB4	PSMB4	PSMB4	6434	0.035	0.48	NO
72	RPS27A	RPS27A	RPS27A	6457	0.035	0.48	NO
73	PSMD2	PSMD2	PSMD2	6470	0.034	0.48	NO
74	NCK1	NCK1	NCK1	6496	0.034	0.48	NO
75	PTEN	PTEN	PTEN	6505	0.034	0.48	NO
76	CHUK	CHUK	CHUK	6563	0.032	0.48	NO
77	BTRC	BTRC	BTRC	6714	0.029	0.47	NO
78	BAD	BAD	BAD	6940	0.024	0.46	NO
79	PSMD11	PSMD11	PSMD11	7009	0.022	0.46	NO
80	CALM3	CALM3	CALM3	7060	0.022	0.46	NO
81	CALM2	CALM2	CALM2	7104	0.02	0.46	NO
82	PSMD1	PSMD1	PSMD1	7278	0.017	0.45	NO
83	KRAS	KRAS	KRAS	7309	0.016	0.45	NO
84	PSMD5	PSMD5	PSMD5	7634	0.0097	0.43	NO
85	RELA	RELA	RELA	7636	0.0097	0.43	NO
86	PSMF1	PSMF1	PSMF1	7810	0.0055	0.42	NO
87	MAPKAP1	MAPKAP1	MAPKAP1	7859	0.0043	0.42	NO
88	PSMD6	PSMD6	PSMD6	7915	0.0031	0.42	NO
89	PSMC6	PSMC6	PSMC6	7969	0.0021	0.42	NO
90	STIM1	STIM1	STIM1	8212	-0.0026	0.4	NO
91	GSK3A	GSK3A	GSK3A	8246	-0.0034	0.4	NO
92	MTOR	MTOR	MTOR	8318	-0.005	0.4	NO
93	PHLPP1	PHLPP1	PHLPP1	8555	-0.01	0.38	NO
94	MALT1	MALT1	MALT1	8610	-0.011	0.38	NO
95	AKT1	AKT1	AKT1	8693	-0.013	0.38	NO
96	AKT2	AKT2	AKT2	8801	-0.016	0.37	NO
97	PSME4	PSME4	PSME4	9281	-0.026	0.35	NO
98	IKBKB	IKBKB	IKBKB	9634	-0.033	0.33	NO
99	FOXO4	FOXO4	FOXO4	9687	-0.034	0.33	NO
100	CALM1	CALM1	CALM1	9879	-0.038	0.32	NO
101	CDKN1A	CDKN1A	CDKN1A	9920	-0.038	0.32	NO
102	FOXO3	FOXO3	FOXO3	9996	-0.04	0.32	NO
103	MAP3K7	MAP3K7	MAP3K7	10070	-0.042	0.32	NO
104	PSMD10	PSMD10	PSMD10	10088	-0.042	0.32	NO
105	SKP1	SKP1	SKP1	10134	-0.043	0.32	NO
106	CREB1	CREB1	CREB1	10640	-0.053	0.3	NO
107	SHC1	SHC1	SHC1	11461	-0.072	0.26	NO
108	CUL1	CUL1	CUL1	11500	-0.073	0.26	NO
109	TSC2	TSC2	TSC2	11623	-0.076	0.26	NO
110	FBXW11	FBXW11	FBXW11	11763	-0.08	0.25	NO
111	REL	REL	REL	12049	-0.087	0.24	NO
112	FOXO1	FOXO1	FOXO1	12071	-0.088	0.25	NO
113	PLCG1	PLCG1	PLCG1	12294	-0.094	0.24	NO
114	SOS1	SOS1	SOS1	12339	-0.095	0.24	NO
115	RICTOR	RICTOR	RICTOR	12945	-0.12	0.22	NO
116	PDPK1	PDPK1	PDPK1	13572	-0.14	0.19	NO
117	PIK3R1	PIK3R1	PIK3R1	13707	-0.14	0.19	NO
118	CDKN1B	CDKN1B	CDKN1B	13945	-0.15	0.19	NO
119	CBL	CBL	CBL	14510	-0.18	0.17	NO
120	NR4A1	NR4A1	NR4A1	15019	-0.2	0.16	NO
121	AKT3	AKT3	AKT3	16353	-0.3	0.1	NO

Figure S5. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PROTEASOME.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROTEASOME, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION

Table S4. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CARD11	CARD11	CARD11	646	0.43	0.039	YES
2	NFKBIE	NFKBIE	NFKBIE	1006	0.34	0.079	YES
3	PSMB9	PSMB9	PSMB9	1057	0.33	0.13	YES
4	PSMB10	PSMB10	PSMB10	1128	0.32	0.18	YES
5	PRKCB	PRKCB	PRKCB	1564	0.26	0.2	YES
6	PSMB8	PSMB8	PSMB8	2232	0.19	0.2	YES
7	PSMA8	PSMA8	PSMA8	2349	0.18	0.23	YES
8	BCL10	BCL10	BCL10	2575	0.16	0.24	YES
9	PSME2	PSME2	PSME2	2662	0.16	0.27	YES
10	NFKBIB	NFKBIB	NFKBIB	3084	0.14	0.27	YES
11	IKBKG	IKBKG	IKBKG	3119	0.13	0.29	YES
12	PSMC1	PSMC1	PSMC1	3141	0.13	0.31	YES
13	PSMB6	PSMB6	PSMB6	3312	0.12	0.32	YES
14	NFKBIA	NFKBIA	NFKBIA	3457	0.12	0.34	YES
15	PSMD13	PSMD13	PSMD13	3578	0.11	0.35	YES
16	PSMB7	PSMB7	PSMB7	3761	0.11	0.36	YES
17	PSMB3	PSMB3	PSMB3	3831	0.1	0.37	YES
18	PSMA6	PSMA6	PSMA6	3864	0.1	0.39	YES
19	PSMA7	PSMA7	PSMA7	3902	0.1	0.4	YES
20	PSME1	PSME1	PSME1	3964	0.1	0.42	YES
21	PSMA5	PSMA5	PSMA5	4193	0.093	0.42	YES
22	PSMA2	PSMA2	PSMA2	4238	0.092	0.44	YES
23	PSMB2	PSMB2	PSMB2	4344	0.088	0.44	YES
24	PSMD14	PSMD14	PSMD14	4517	0.082	0.45	YES
25	PSMA1	PSMA1	PSMA1	4550	0.081	0.46	YES
26	PSMC4	PSMC4	PSMC4	4588	0.08	0.47	YES
27	UBA52	UBA52	UBA52	4613	0.079	0.49	YES
28	PSMC2	PSMC2	PSMC2	4628	0.079	0.5	YES
29	PSMA3	PSMA3	PSMA3	4730	0.076	0.51	YES
30	PSMB1	PSMB1	PSMB1	4783	0.075	0.52	YES
31	PSMD7	PSMD7	PSMD7	4966	0.07	0.52	YES
32	PSMC3	PSMC3	PSMC3	5066	0.068	0.53	YES
33	PSMC5	PSMC5	PSMC5	5078	0.067	0.54	YES
34	PSMA4	PSMA4	PSMA4	5165	0.065	0.54	YES
35	PSMD9	PSMD9	PSMD9	5262	0.062	0.55	YES
36	PSMD8	PSMD8	PSMD8	5360	0.06	0.56	YES
37	PSMD12	PSMD12	PSMD12	5434	0.058	0.56	YES
38	PSMD3	PSMD3	PSMD3	5875	0.047	0.55	NO
39	PSMD4	PSMD4	PSMD4	5948	0.046	0.55	NO
40	PSMB5	PSMB5	PSMB5	6231	0.039	0.54	NO
41	PSMB4	PSMB4	PSMB4	6434	0.035	0.54	NO
42	RPS27A	RPS27A	RPS27A	6457	0.035	0.54	NO
43	PSMD2	PSMD2	PSMD2	6470	0.034	0.55	NO
44	CHUK	CHUK	CHUK	6563	0.032	0.55	NO
45	BTRC	BTRC	BTRC	6714	0.029	0.54	NO
46	PSMD11	PSMD11	PSMD11	7009	0.022	0.53	NO
47	PSMD1	PSMD1	PSMD1	7278	0.017	0.52	NO
48	PSMD5	PSMD5	PSMD5	7634	0.0097	0.5	NO
49	RELA	RELA	RELA	7636	0.0097	0.5	NO
50	PSMF1	PSMF1	PSMF1	7810	0.0055	0.49	NO
51	PSMD6	PSMD6	PSMD6	7915	0.0031	0.49	NO
52	PSMC6	PSMC6	PSMC6	7969	0.0021	0.49	NO
53	MALT1	MALT1	MALT1	8610	-0.011	0.45	NO
54	PSME4	PSME4	PSME4	9281	-0.026	0.42	NO
55	IKBKB	IKBKB	IKBKB	9634	-0.033	0.41	NO
56	MAP3K7	MAP3K7	MAP3K7	10070	-0.042	0.39	NO
57	PSMD10	PSMD10	PSMD10	10088	-0.042	0.4	NO
58	SKP1	SKP1	SKP1	10134	-0.043	0.4	NO
59	CUL1	CUL1	CUL1	11500	-0.073	0.34	NO
60	FBXW11	FBXW11	FBXW11	11763	-0.08	0.34	NO
61	REL	REL	REL	12049	-0.087	0.34	NO

Figure S7. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG CHEMOKINE SIGNALING PATHWAY

Table S5. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HK3	HK3	HK3	12	0.85	0.12	YES
2	GFPT2	GFPT2	GFPT2	107	0.66	0.21	YES
3	NPL	NPL	NPL	141	0.63	0.3	YES
4	RENBP	RENBP	RENBP	316	0.54	0.37	YES
5	UAP1	UAP1	UAP1	1021	0.33	0.38	YES
6	UGDH	UGDH	UGDH	1251	0.3	0.41	YES
7	NANS	NANS	NANS	1538	0.26	0.43	YES
8	AMDHD2	AMDHD2	AMDHD2	1843	0.22	0.44	YES
9	PMM2	PMM2	PMM2	2070	0.2	0.46	YES
10	GALK1	GALK1	GALK1	2153	0.19	0.48	YES
11	HK2	HK2	HK2	2260	0.18	0.5	YES
12	HEXA	HEXA	HEXA	2364	0.18	0.52	YES
13	CHIT1	CHIT1	CHIT1	2379	0.18	0.55	YES
14	GNPNAT1	GNPNAT1	GNPNAT1	2517	0.17	0.56	YES
15	NAGK	NAGK	NAGK	2711	0.16	0.58	YES
16	PGM3	PGM3	PGM3	2800	0.15	0.59	YES
17	GMPPA	GMPPA	GMPPA	3339	0.12	0.58	NO
18	GMPPB	GMPPB	GMPPB	4037	0.098	0.56	NO
19	GALE	GALE	GALE	4055	0.097	0.57	NO
20	HEXB	HEXB	HEXB	4126	0.096	0.58	NO
21	UGP2	UGP2	UGP2	4860	0.073	0.55	NO
22	GMDS	GMDS	GMDS	5874	0.047	0.5	NO
23	PMM1	PMM1	PMM1	5973	0.045	0.5	NO
24	HK1	HK1	HK1	6018	0.044	0.51	NO
25	UXS1	UXS1	UXS1	6295	0.038	0.5	NO
26	GALK2	GALK2	GALK2	6664	0.03	0.48	NO
27	GNPDA1	GNPDA1	GNPDA1	6692	0.03	0.48	NO
28	CYB5R3	CYB5R3	CYB5R3	7025	0.022	0.47	NO
29	NANP	NANP	NANP	7335	0.016	0.45	NO
30	TSTA3	TSTA3	TSTA3	7838	0.0049	0.43	NO
31	GFPT1	GFPT1	GFPT1	7878	0.0038	0.42	NO
32	PGM1	PGM1	PGM1	7991	0.0016	0.42	NO
33	GPI	GPI	GPI	8309	-0.0047	0.4	NO
34	CYB5R1	CYB5R1	CYB5R1	9470	-0.03	0.34	NO
35	GNE	GNE	GNE	10331	-0.047	0.3	NO
36	MPI	MPI	MPI	10433	-0.049	0.3	NO
37	FPGT	FPGT	FPGT	11034	-0.063	0.28	NO
38	FUK	FUK	FUK	11106	-0.064	0.28	NO
39	CMAS	CMAS	CMAS	11187	-0.066	0.29	NO
40	GALT	GALT	GALT	11730	-0.079	0.27	NO
41	GNPDA2	GNPDA2	GNPDA2	12000	-0.086	0.27	NO
42	PGM2	PGM2	PGM2	12637	-0.1	0.25	NO
43	GCK	GCK	GCK	17130	-0.4	0.057	NO

Figure S9. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CHEMOKINE SIGNALING PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CHEMOKINE SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG LYSOSOME

Table S6. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD68	CD68	CD68	300	0.55	0.014	YES
2	CTSW	CTSW	CTSW	326	0.54	0.042	YES
3	LAPTM5	LAPTM5	LAPTM5	496	0.48	0.059	YES
4	CTSS	CTSS	CTSS	506	0.47	0.084	YES
5	CTSC	CTSC	CTSC	526	0.46	0.11	YES
6	ACP5	ACP5	ACP5	633	0.43	0.13	YES
7	PLA2G15	PLA2G15	PLA2G15	849	0.37	0.14	YES
8	FUCA1	FUCA1	FUCA1	946	0.35	0.15	YES
9	SLC11A1	SLC11A1	SLC11A1	963	0.35	0.17	YES
10	LGMN	LGMN	LGMN	975	0.34	0.19	YES
11	LAMP3	LAMP3	LAMP3	1103	0.32	0.2	YES
12	CTSZ	CTSZ	CTSZ	1292	0.29	0.2	YES
13	NAPSA	NAPSA	NAPSA	1512	0.26	0.2	YES
14	NAGPA	NAGPA	NAGPA	1567	0.25	0.22	YES
15	ATP6V0D2	ATP6V0D2	ATP6V0D2	1577	0.25	0.23	YES
16	CTSL1	CTSL1	CTSL1	1581	0.25	0.24	YES
17	NPC2	NPC2	NPC2	1669	0.24	0.25	YES
18	LIPA	LIPA	LIPA	1686	0.24	0.26	YES
19	GALC	GALC	GALC	1699	0.24	0.28	YES
20	CTSH	CTSH	CTSH	1729	0.24	0.29	YES
21	CTSB	CTSB	CTSB	1800	0.23	0.3	YES
22	MANBA	MANBA	MANBA	1966	0.21	0.3	YES
23	ACP2	ACP2	ACP2	2045	0.2	0.31	YES
24	CTSD	CTSD	CTSD	2114	0.2	0.31	YES
25	MAN2B1	MAN2B1	MAN2B1	2182	0.19	0.32	YES
26	IDUA	IDUA	IDUA	2203	0.19	0.33	YES
27	GLA	GLA	GLA	2257	0.18	0.34	YES
28	ARSA	ARSA	ARSA	2337	0.18	0.34	YES
29	HEXA	HEXA	HEXA	2364	0.18	0.35	YES
30	GALNS	GALNS	GALNS	2369	0.18	0.36	YES
31	CTNS	CTNS	CTNS	2376	0.18	0.37	YES
32	CTSA	CTSA	CTSA	2378	0.18	0.38	YES
33	NEU1	NEU1	NEU1	2489	0.17	0.38	YES
34	MCOLN1	MCOLN1	MCOLN1	2496	0.17	0.39	YES
35	AP1B1	AP1B1	AP1B1	2551	0.17	0.4	YES
36	SLC17A5	SLC17A5	SLC17A5	2618	0.16	0.4	YES
37	TCIRG1	TCIRG1	TCIRG1	2632	0.16	0.41	YES
38	PSAP	PSAP	PSAP	2687	0.16	0.42	YES
39	ATP6V0B	ATP6V0B	ATP6V0B	2763	0.15	0.42	YES
40	CTSG	CTSG	CTSG	2888	0.15	0.42	YES
41	NAGLU	NAGLU	NAGLU	2929	0.14	0.43	YES
42	ATP6V0D1	ATP6V0D1	ATP6V0D1	3016	0.14	0.43	YES
43	GNPTAB	GNPTAB	GNPTAB	3042	0.14	0.44	YES
44	TPP1	TPP1	TPP1	3125	0.13	0.44	YES
45	SMPD1	SMPD1	SMPD1	3250	0.13	0.44	YES
46	HYAL1	HYAL1	HYAL1	3295	0.13	0.44	YES
47	GBA	GBA	GBA	3297	0.13	0.45	YES
48	ATP6V0C	ATP6V0C	ATP6V0C	3335	0.12	0.46	YES
49	CLTA	CLTA	CLTA	3356	0.12	0.46	YES
50	DNASE2B	DNASE2B	DNASE2B	3366	0.12	0.47	YES
51	NAGA	NAGA	NAGA	3368	0.12	0.48	YES
52	CD63	CD63	CD63	3394	0.12	0.48	YES
53	ATP6AP1	ATP6AP1	ATP6AP1	3421	0.12	0.48	YES
54	GLB1	GLB1	GLB1	3531	0.12	0.48	YES
55	DNASE2	DNASE2	DNASE2	3548	0.11	0.49	YES
56	ASAH1	ASAH1	ASAH1	3584	0.11	0.5	YES
57	GNPTG	GNPTG	GNPTG	3596	0.11	0.5	YES
58	AP3S1	AP3S1	AP3S1	3658	0.11	0.5	YES
59	LAMP1	LAMP1	LAMP1	3680	0.11	0.51	YES
60	LAMP2	LAMP2	LAMP2	3694	0.11	0.51	YES
61	SGSH	SGSH	SGSH	3742	0.11	0.52	YES
62	GM2A	GM2A	GM2A	3748	0.11	0.52	YES
63	CLN3	CLN3	CLN3	3957	0.1	0.52	NO
64	HEXB	HEXB	HEXB	4126	0.096	0.51	NO
65	CTSO	CTSO	CTSO	4237	0.092	0.51	NO
66	SUMF1	SUMF1	SUMF1	4295	0.09	0.51	NO
67	GAA	GAA	GAA	4573	0.08	0.5	NO
68	GNS	GNS	GNS	4705	0.077	0.5	NO
69	M6PR	M6PR	M6PR	4724	0.077	0.5	NO
70	LAPTM4A	LAPTM4A	LAPTM4A	4841	0.074	0.5	NO
71	AGA	AGA	AGA	4850	0.073	0.5	NO
72	GUSB	GUSB	GUSB	4874	0.073	0.51	NO
73	AP1S1	AP1S1	AP1S1	4967	0.07	0.5	NO
74	AP1M1	AP1M1	AP1M1	5145	0.066	0.5	NO
75	CLTB	CLTB	CLTB	5236	0.063	0.5	NO
76	GGA3	GGA3	GGA3	5385	0.06	0.49	NO
77	ATP6V0A2	ATP6V0A2	ATP6V0A2	5612	0.054	0.48	NO
78	IGF2R	IGF2R	IGF2R	5823	0.048	0.47	NO
79	AP4B1	AP4B1	AP4B1	5956	0.046	0.47	NO
80	CD164	CD164	CD164	5962	0.046	0.47	NO
81	AP1S2	AP1S2	AP1S2	6397	0.036	0.45	NO
82	CLTC	CLTC	CLTC	6567	0.032	0.44	NO
83	CLN5	CLN5	CLN5	6629	0.031	0.44	NO
84	PPT1	PPT1	PPT1	6822	0.027	0.43	NO
85	SCARB2	SCARB2	SCARB2	6856	0.026	0.43	NO
86	AP3B1	AP3B1	AP3B1	7139	0.02	0.42	NO
87	GGA2	GGA2	GGA2	7261	0.018	0.41	NO
88	GGA1	GGA1	GGA1	7500	0.013	0.4	NO
89	NPC1	NPC1	NPC1	7544	0.012	0.4	NO
90	IDS	IDS	IDS	7889	0.0036	0.38	NO
91	AP1G1	AP1G1	AP1G1	7952	0.0023	0.37	NO
92	AP3M1	AP3M1	AP3M1	8567	-0.011	0.34	NO
93	AP4E1	AP4E1	AP4E1	8738	-0.014	0.33	NO
94	AP1S3	AP1S3	AP1S3	8767	-0.015	0.33	NO
95	AP3D1	AP3D1	AP3D1	8783	-0.015	0.33	NO
96	CLTCL1	CLTCL1	CLTCL1	9075	-0.022	0.32	NO
97	ATP6V0A1	ATP6V0A1	ATP6V0A1	9091	-0.022	0.32	NO
98	AP3S2	AP3S2	AP3S2	9312	-0.027	0.31	NO
99	AP4M1	AP4M1	AP4M1	9734	-0.035	0.28	NO
100	CTSK	CTSK	CTSK	9795	-0.036	0.28	NO
101	PPT2	PPT2	PPT2	10147	-0.043	0.27	NO
102	SLC11A2	SLC11A2	SLC11A2	10155	-0.043	0.27	NO
103	MFSD8	MFSD8	MFSD8	10714	-0.055	0.24	NO
104	ENTPD4	ENTPD4	ENTPD4	10744	-0.056	0.24	NO
105	AP4S1	AP4S1	AP4S1	10772	-0.056	0.24	NO
106	HGSNAT	HGSNAT	HGSNAT	10816	-0.058	0.24	NO
107	CTSE	CTSE	CTSE	11146	-0.065	0.23	NO
108	LAPTM4B	LAPTM4B	LAPTM4B	11201	-0.066	0.23	NO
109	ATP6V1H	ATP6V1H	ATP6V1H	11496	-0.073	0.22	NO
110	AP3M2	AP3M2	AP3M2	11667	-0.077	0.21	NO
111	ARSG	ARSG	ARSG	11793	-0.08	0.21	NO
112	ARSB	ARSB	ARSB	12401	-0.097	0.18	NO
113	CTSF	CTSF	CTSF	13250	-0.12	0.14	NO
114	ABCA2	ABCA2	ABCA2	13782	-0.14	0.12	NO
115	AP1M2	AP1M2	AP1M2	15001	-0.2	0.064	NO
116	ABCB9	ABCB9	ABCB9	15386	-0.23	0.056	NO
117	ATP6V0A4	ATP6V0A4	ATP6V0A4	15843	-0.26	0.044	NO
118	SORT1	SORT1	SORT1	16514	-0.32	0.025	NO
119	AP3B2	AP3B2	AP3B2	17613	-0.51	-0.008	NO
120	CTSL2	CTSL2	CTSL2	18037	-0.7	0.0073	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG LYSOSOME.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSOSOME, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG APOPTOSIS

Table S7. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PSMB9	PSMB9	PSMB9	1057	0.33	0.0003	YES
2	PSMB10	PSMB10	PSMB10	1128	0.32	0.053	YES
3	TNFSF13	TNFSF13	TNFSF13	1579	0.25	0.074	YES
4	PSMB8	PSMB8	PSMB8	2232	0.19	0.071	YES
5	PSMA8	PSMA8	PSMA8	2349	0.18	0.097	YES
6	PSME2	PSME2	PSME2	2662	0.16	0.11	YES
7	EXOSC1	EXOSC1	EXOSC1	3087	0.14	0.11	YES
8	PSMC1	PSMC1	PSMC1	3141	0.13	0.13	YES
9	PSMB6	PSMB6	PSMB6	3312	0.12	0.14	YES
10	EXOSC5	EXOSC5	EXOSC5	3318	0.12	0.16	YES
11	PSMD13	PSMD13	PSMD13	3578	0.11	0.17	YES
12	PSMB7	PSMB7	PSMB7	3761	0.11	0.18	YES
13	EXOSC7	EXOSC7	EXOSC7	3769	0.11	0.2	YES
14	PSMB3	PSMB3	PSMB3	3831	0.1	0.22	YES
15	PSMA6	PSMA6	PSMA6	3864	0.1	0.23	YES
16	PSMA7	PSMA7	PSMA7	3902	0.1	0.25	YES
17	PSME1	PSME1	PSME1	3964	0.1	0.26	YES
18	EXOSC4	EXOSC4	EXOSC4	3966	0.1	0.28	YES
19	PSMA5	PSMA5	PSMA5	4193	0.093	0.28	YES
20	PSMA2	PSMA2	PSMA2	4238	0.092	0.3	YES
21	PSMB2	PSMB2	PSMB2	4344	0.088	0.31	YES
22	PSMD14	PSMD14	PSMD14	4517	0.082	0.31	YES
23	PSMA1	PSMA1	PSMA1	4550	0.081	0.33	YES
24	PSMC4	PSMC4	PSMC4	4588	0.08	0.34	YES
25	UBA52	UBA52	UBA52	4613	0.079	0.35	YES
26	PSMC2	PSMC2	PSMC2	4628	0.079	0.36	YES
27	ZFP36	ZFP36	ZFP36	4640	0.079	0.38	YES
28	PSMA3	PSMA3	PSMA3	4730	0.076	0.39	YES
29	PSMB1	PSMB1	PSMB1	4783	0.075	0.4	YES
30	YWHAB	YWHAB	YWHAB	4958	0.07	0.4	YES
31	PSMD7	PSMD7	PSMD7	4966	0.07	0.41	YES
32	PSMC3	PSMC3	PSMC3	5066	0.068	0.42	YES
33	PSMC5	PSMC5	PSMC5	5078	0.067	0.43	YES
34	PSMA4	PSMA4	PSMA4	5165	0.065	0.44	YES
35	HSPA1B	HSPA1B	HSPA1B	5192	0.064	0.45	YES
36	PSMD9	PSMD9	PSMD9	5262	0.062	0.46	YES
37	EXOSC6	EXOSC6	EXOSC6	5286	0.062	0.47	YES
38	PSMD8	PSMD8	PSMD8	5360	0.06	0.47	YES
39	PSMD12	PSMD12	PSMD12	5434	0.058	0.48	YES
40	PRKCD	PRKCD	PRKCD	5824	0.048	0.47	YES
41	PSMD3	PSMD3	PSMD3	5875	0.047	0.47	YES
42	PSMD4	PSMD4	PSMD4	5948	0.046	0.48	YES
43	EXOSC3	EXOSC3	EXOSC3	6086	0.042	0.48	YES
44	PSMB5	PSMB5	PSMB5	6231	0.039	0.48	YES
45	PSMB4	PSMB4	PSMB4	6434	0.035	0.47	YES
46	RPS27A	RPS27A	RPS27A	6457	0.035	0.48	YES
47	PSMD2	PSMD2	PSMD2	6470	0.034	0.48	YES
48	MAPKAPK2	MAPKAPK2	MAPKAPK2	6672	0.03	0.48	NO
49	PRKCA	PRKCA	PRKCA	6690	0.03	0.48	NO
50	EXOSC8	EXOSC8	EXOSC8	6764	0.028	0.48	NO
51	PABPC1	PABPC1	PABPC1	6931	0.024	0.48	NO
52	PSMD11	PSMD11	PSMD11	7009	0.022	0.48	NO
53	ZFP36L1	ZFP36L1	ZFP36L1	7152	0.019	0.47	NO
54	PSMD1	PSMD1	PSMD1	7278	0.017	0.47	NO
55	MAPK14	MAPK14	MAPK14	7518	0.012	0.46	NO
56	PSMD5	PSMD5	PSMD5	7634	0.0097	0.45	NO
57	EIF4G1	EIF4G1	EIF4G1	7668	0.0087	0.45	NO
58	DCP2	DCP2	DCP2	7705	0.0078	0.45	NO
59	PSMF1	PSMF1	PSMF1	7810	0.0055	0.45	NO
60	HSPA8	HSPA8	HSPA8	7890	0.0036	0.44	NO
61	PSMD6	PSMD6	PSMD6	7915	0.0031	0.44	NO
62	PSMC6	PSMC6	PSMC6	7969	0.0021	0.44	NO
63	EXOSC9	EXOSC9	EXOSC9	8376	-0.0063	0.42	NO
64	EXOSC2	EXOSC2	EXOSC2	8425	-0.0072	0.42	NO
65	HNRNPD	HNRNPD	HNRNPD	8514	-0.0093	0.41	NO
66	AKT1	AKT1	AKT1	8693	-0.013	0.41	NO
67	PARN	PARN	PARN	8958	-0.019	0.4	NO
68	XRN1	XRN1	XRN1	8967	-0.019	0.4	NO
69	TNPO1	TNPO1	TNPO1	9232	-0.025	0.39	NO
70	ANP32A	ANP32A	ANP32A	9236	-0.025	0.39	NO
71	PSME4	PSME4	PSME4	9281	-0.026	0.39	NO
72	NUP214	NUP214	NUP214	9284	-0.026	0.4	NO
73	ELAVL1	ELAVL1	ELAVL1	9371	-0.028	0.4	NO
74	KHSRP	KHSRP	KHSRP	9645	-0.033	0.39	NO
75	YWHAZ	YWHAZ	YWHAZ	9716	-0.034	0.39	NO
76	PSMD10	PSMD10	PSMD10	10088	-0.042	0.38	NO
77	HSPB1	HSPB1	HSPB1	10558	-0.051	0.36	NO
78	DIS3	DIS3	DIS3	10855	-0.058	0.36	NO
79	XPO1	XPO1	XPO1	11433	-0.071	0.34	NO
80	MAPK11	MAPK11	MAPK11	11460	-0.072	0.35	NO
81	DCP1A	DCP1A	DCP1A	13191	-0.12	0.28	NO

Figure S13. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG APOPTOSIS.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG APOPTOSIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG COMPLEMENT AND COAGULATION CASCADES

Table S8. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PSMB9	PSMB9	PSMB9	1057	0.33	0.027	YES
2	PSMB10	PSMB10	PSMB10	1128	0.32	0.11	YES
3	PSMB8	PSMB8	PSMB8	2232	0.19	0.094	YES
4	PSMA8	PSMA8	PSMA8	2349	0.18	0.14	YES
5	PSME2	PSME2	PSME2	2662	0.16	0.16	YES
6	PSMC1	PSMC1	PSMC1	3141	0.13	0.17	YES
7	PSMB6	PSMB6	PSMB6	3312	0.12	0.19	YES
8	PSMD13	PSMD13	PSMD13	3578	0.11	0.21	YES
9	PSMB7	PSMB7	PSMB7	3761	0.11	0.22	YES
10	PSMB3	PSMB3	PSMB3	3831	0.1	0.25	YES
11	PSMA6	PSMA6	PSMA6	3864	0.1	0.27	YES
12	PSMA7	PSMA7	PSMA7	3902	0.1	0.3	YES
13	PSME1	PSME1	PSME1	3964	0.1	0.32	YES
14	PSMA5	PSMA5	PSMA5	4193	0.093	0.33	YES
15	PSMA2	PSMA2	PSMA2	4238	0.092	0.35	YES
16	PSMB2	PSMB2	PSMB2	4344	0.088	0.37	YES
17	PSMD14	PSMD14	PSMD14	4517	0.082	0.38	YES
18	PSMA1	PSMA1	PSMA1	4550	0.081	0.4	YES
19	PSMC4	PSMC4	PSMC4	4588	0.08	0.42	YES
20	UBA52	UBA52	UBA52	4613	0.079	0.44	YES
21	PSMC2	PSMC2	PSMC2	4628	0.079	0.46	YES
22	PSMA3	PSMA3	PSMA3	4730	0.076	0.48	YES
23	PSMB1	PSMB1	PSMB1	4783	0.075	0.49	YES
24	PSMD7	PSMD7	PSMD7	4966	0.07	0.5	YES
25	PSMC3	PSMC3	PSMC3	5066	0.068	0.51	YES
26	PSMC5	PSMC5	PSMC5	5078	0.067	0.53	YES
27	PSMA4	PSMA4	PSMA4	5165	0.065	0.54	YES
28	PSMD9	PSMD9	PSMD9	5262	0.062	0.55	YES
29	PSMD8	PSMD8	PSMD8	5360	0.06	0.56	YES
30	PSMD12	PSMD12	PSMD12	5434	0.058	0.58	YES
31	PSMD3	PSMD3	PSMD3	5875	0.047	0.56	YES
32	PSMD4	PSMD4	PSMD4	5948	0.046	0.57	YES
33	PSMB5	PSMB5	PSMB5	6231	0.039	0.57	YES
34	PSMB4	PSMB4	PSMB4	6434	0.035	0.56	YES
35	RPS27A	RPS27A	RPS27A	6457	0.035	0.57	YES
36	PSMD2	PSMD2	PSMD2	6470	0.034	0.58	YES
37	PSMD11	PSMD11	PSMD11	7009	0.022	0.56	NO
38	PSMD1	PSMD1	PSMD1	7278	0.017	0.55	NO
39	PSMD5	PSMD5	PSMD5	7634	0.0097	0.53	NO
40	RFWD2	RFWD2	RFWD2	7693	0.008	0.53	NO
41	PSMF1	PSMF1	PSMF1	7810	0.0055	0.52	NO
42	PSMD6	PSMD6	PSMD6	7915	0.0031	0.52	NO
43	PSMC6	PSMC6	PSMC6	7969	0.0021	0.52	NO
44	TP53	TP53	TP53	8862	-0.017	0.47	NO
45	PSME4	PSME4	PSME4	9281	-0.026	0.46	NO
46	PSMD10	PSMD10	PSMD10	10088	-0.042	0.42	NO
47	ATM	ATM	ATM	12243	-0.093	0.33	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG COMPLEMENT AND COAGULATION CASCADES.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG COMPLEMENT AND COAGULATION CASCADES, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG ANTIGEN PROCESSING AND PRESENTATION

Table S9. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NCF1	NCF1	NCF1	28	0.78	0.039	YES
2	VAV1	VAV1	VAV1	42	0.76	0.078	YES
3	FCGR1A	FCGR1A	FCGR1A	53	0.74	0.12	YES
4	HCK	HCK	HCK	90	0.68	0.15	YES
5	WAS	WAS	WAS	104	0.66	0.18	YES
6	PIK3R5	PIK3R5	PIK3R5	242	0.57	0.2	YES
7	FCGR2B	FCGR2B	FCGR2B	245	0.57	0.24	YES
8	FCGR2C	FCGR2C	FCGR2C	276	0.56	0.26	YES
9	SYK	SYK	SYK	323	0.54	0.29	YES
10	DOCK2	DOCK2	DOCK2	335	0.53	0.32	YES
11	FCGR3A	FCGR3A	FCGR3A	340	0.53	0.34	YES
12	RAC2	RAC2	RAC2	371	0.52	0.37	YES
13	PIK3CG	PIK3CG	PIK3CG	421	0.5	0.39	YES
14	PTPRC	PTPRC	PTPRC	505	0.47	0.41	YES
15	FCGR2A	FCGR2A	FCGR2A	516	0.47	0.44	YES
16	INPP5D	INPP5D	INPP5D	650	0.43	0.45	YES
17	PIK3CD	PIK3CD	PIK3CD	717	0.41	0.47	YES
18	ASAP3	ASAP3	ASAP3	774	0.4	0.48	YES
19	LYN	LYN	LYN	877	0.36	0.5	YES
20	DNM1	DNM1	DNM1	921	0.35	0.51	YES
21	SCIN	SCIN	SCIN	1300	0.29	0.51	YES
22	ARPC1B	ARPC1B	ARPC1B	1349	0.28	0.52	YES
23	LIMK1	LIMK1	LIMK1	1372	0.28	0.53	YES
24	SPHK1	SPHK1	SPHK1	1380	0.28	0.55	YES
25	PLCG2	PLCG2	PLCG2	1455	0.27	0.56	YES
26	LAT	LAT	LAT	1531	0.26	0.57	YES
27	PRKCB	PRKCB	PRKCB	1564	0.26	0.58	YES
28	MARCKS	MARCKS	MARCKS	1665	0.24	0.59	YES
29	PLA2G4A	PLA2G4A	PLA2G4A	2139	0.19	0.57	NO
30	ARPC3	ARPC3	ARPC3	2700	0.16	0.55	NO
31	PPAP2B	PPAP2B	PPAP2B	3258	0.13	0.52	NO
32	ARPC5L	ARPC5L	ARPC5L	3587	0.11	0.51	NO
33	ARF6	ARF6	ARF6	3790	0.11	0.5	NO
34	CDC42	CDC42	CDC42	3914	0.1	0.5	NO
35	ARPC4	ARPC4	ARPC4	4140	0.095	0.5	NO
36	CFL1	CFL1	CFL1	4232	0.092	0.5	NO
37	MAPK3	MAPK3	MAPK3	4418	0.086	0.49	NO
38	ARPC2	ARPC2	ARPC2	4650	0.078	0.48	NO
39	RAC1	RAC1	RAC1	5148	0.066	0.46	NO
40	RPS6KB2	RPS6KB2	RPS6KB2	5314	0.061	0.45	NO
41	PLD2	PLD2	PLD2	5317	0.061	0.45	NO
42	DNM2	DNM2	DNM2	5530	0.056	0.44	NO
43	ARPC5	ARPC5	ARPC5	5621	0.054	0.44	NO
44	SPHK2	SPHK2	SPHK2	5714	0.051	0.44	NO
45	PRKCD	PRKCD	PRKCD	5824	0.048	0.44	NO
46	PAK1	PAK1	PAK1	5827	0.048	0.44	NO
47	VAV3	VAV3	VAV3	6112	0.042	0.43	NO
48	MAP2K1	MAP2K1	MAP2K1	6279	0.038	0.42	NO
49	PRKCA	PRKCA	PRKCA	6690	0.03	0.4	NO
50	ARPC1A	ARPC1A	ARPC1A	6799	0.027	0.39	NO
51	PLD1	PLD1	PLD1	7035	0.022	0.38	NO
52	ASAP2	ASAP2	ASAP2	7207	0.018	0.37	NO
53	PIK3R2	PIK3R2	PIK3R2	7228	0.018	0.37	NO
54	CRK	CRK	CRK	7334	0.016	0.37	NO
55	WASF3	WASF3	WASF3	7676	0.0084	0.35	NO
56	ASAP1	ASAP1	ASAP1	7756	0.0068	0.34	NO
57	WASL	WASL	WASL	8529	-0.0097	0.3	NO
58	PRKCE	PRKCE	PRKCE	8639	-0.012	0.3	NO
59	AKT1	AKT1	AKT1	8693	-0.013	0.3	NO
60	CRKL	CRKL	CRKL	8717	-0.014	0.3	NO
61	AKT2	AKT2	AKT2	8801	-0.016	0.29	NO
62	MAPK1	MAPK1	MAPK1	9010	-0.02	0.28	NO
63	RPS6KB1	RPS6KB1	RPS6KB1	9018	-0.02	0.28	NO
64	WASF2	WASF2	WASF2	9110	-0.022	0.28	NO
65	PIP5K1C	PIP5K1C	PIP5K1C	9277	-0.026	0.27	NO
66	RAF1	RAF1	RAF1	9695	-0.034	0.25	NO
67	VASP	VASP	VASP	9737	-0.035	0.25	NO
68	GSN	GSN	GSN	9825	-0.036	0.24	NO
69	VAV2	VAV2	VAV2	10090	-0.042	0.23	NO
70	PIK3CB	PIK3CB	PIK3CB	10663	-0.054	0.2	NO
71	PIK3CA	PIK3CA	PIK3CA	11114	-0.064	0.18	NO
72	LIMK2	LIMK2	LIMK2	11124	-0.065	0.18	NO
73	GAB2	GAB2	GAB2	11271	-0.068	0.18	NO
74	PPAP2A	PPAP2A	PPAP2A	11624	-0.076	0.16	NO
75	MYO10	MYO10	MYO10	11870	-0.082	0.16	NO
76	PIP4K2B	PIP4K2B	PIP4K2B	12220	-0.092	0.14	NO
77	PLCG1	PLCG1	PLCG1	12294	-0.094	0.14	NO
78	DNM1L	DNM1L	DNM1L	12678	-0.1	0.13	NO
79	PIP5K1A	PIP5K1A	PIP5K1A	13020	-0.12	0.11	NO
80	MARCKSL1	MARCKSL1	MARCKSL1	13045	-0.12	0.12	NO
81	PIKFYVE	PIKFYVE	PIKFYVE	13061	-0.12	0.12	NO
82	PIK3R1	PIK3R1	PIK3R1	13707	-0.14	0.095	NO
83	PIK3R3	PIK3R3	PIK3R3	13972	-0.15	0.089	NO
84	AMPH	AMPH	AMPH	14148	-0.16	0.087	NO
85	PLA2G6	PLA2G6	PLA2G6	14356	-0.17	0.085	NO
86	WASF1	WASF1	WASF1	14846	-0.2	0.068	NO
87	PLA2G4F	PLA2G4F	PLA2G4F	15047	-0.21	0.068	NO
88	PLA2G4D	PLA2G4D	PLA2G4D	15401	-0.23	0.06	NO
89	CFL2	CFL2	CFL2	15459	-0.23	0.069	NO
90	PPAP2C	PPAP2C	PPAP2C	16151	-0.29	0.045	NO
91	DNM3	DNM3	DNM3	16170	-0.29	0.059	NO
92	PRKCG	PRKCG	PRKCG	16183	-0.29	0.074	NO
93	AKT3	AKT3	AKT3	16353	-0.3	0.08	NO
94	PIP5K1B	PIP5K1B	PIP5K1B	17104	-0.39	0.059	NO

Figure S17. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ANTIGEN PROCESSING AND PRESENTATION.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ANTIGEN PROCESSING AND PRESENTATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG TOLL LIKE RECEPTOR SIGNALING PATHWAY

Table S10. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IKBKE	IKBKE	IKBKE	1399	0.28	0.034	YES
2	ISG15	ISG15	ISG15	1585	0.25	0.12	YES
3	RNF125	RNF125	RNF125	1849	0.22	0.2	YES
4	UBE2L6	UBE2L6	UBE2L6	1931	0.21	0.28	YES
5	TRAF3	TRAF3	TRAF3	2194	0.19	0.34	YES
6	NLRC5	NLRC5	NLRC5	2530	0.17	0.39	YES
7	UBE2D1	UBE2D1	UBE2D1	3151	0.13	0.41	YES
8	TNFAIP3	TNFAIP3	TNFAIP3	3353	0.12	0.45	YES
9	RNF135	RNF135	RNF135	3798	0.11	0.46	YES
10	IRF3	IRF3	IRF3	4063	0.097	0.49	YES
11	UBA7	UBA7	UBA7	4074	0.097	0.53	YES
12	IFIH1	IFIH1	IFIH1	4109	0.096	0.56	YES
13	UBA52	UBA52	UBA52	4613	0.079	0.57	YES
14	OTUD5	OTUD5	OTUD5	6401	0.036	0.48	NO
15	RPS27A	RPS27A	RPS27A	6457	0.035	0.49	NO
16	ATG5	ATG5	ATG5	6699	0.03	0.49	NO
17	UBE2D3	UBE2D3	UBE2D3	6738	0.029	0.5	NO
18	TRIM25	TRIM25	TRIM25	6806	0.027	0.51	NO
19	PCBP2	PCBP2	PCBP2	7316	0.016	0.49	NO
20	ATG12	ATG12	ATG12	7322	0.016	0.49	NO
21	TBK1	TBK1	TBK1	7961	0.0022	0.46	NO
22	DDX58	DDX58	DDX58	8430	-0.0074	0.44	NO
23	UBE2K	UBE2K	UBE2K	8460	-0.008	0.44	NO
24	UBE2D2	UBE2D2	UBE2D2	8510	-0.0092	0.44	NO
25	CYLD	CYLD	CYLD	8550	-0.01	0.44	NO
26	TAX1BP1	TAX1BP1	TAX1BP1	8975	-0.019	0.43	NO
27	PIN1	PIN1	PIN1	9139	-0.023	0.43	NO
28	MAVS	MAVS	MAVS	9533	-0.031	0.42	NO
29	NLRX1	NLRX1	NLRX1	9615	-0.032	0.42	NO
30	HERC5	HERC5	HERC5	12957	-0.12	0.29	NO

Figure S19. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG TOLL LIKE RECEPTOR SIGNALING PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG TOLL LIKE RECEPTOR SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Subtype clus2 enriched pathways

Table 4. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus2. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG LYSINE DEGRADATION	44	genes.ES.table	0.47	1.8	0.004	0.68	0.54	0.46	0.29	0.32	0.23	0.16
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.52	1.7	0.016	0.76	0.76	0.53	0.32	0.36	0.34	0.21
KEGG BUTANOATE METABOLISM	31	genes.ES.table	0.64	1.8	0.0042	0.68	0.62	0.52	0.24	0.39	0.25	0.17
KEGG VASCULAR SMOOTH MUSCLE CONTRACTION	107	genes.ES.table	0.52	1.7	0.0042	0.73	0.87	0.21	0.068	0.19	0.4	0.22
KEGG INSULIN SIGNALING PATHWAY	131	genes.ES.table	0.37	1.5	0.028	0.93	0.98	0.33	0.24	0.25	0.67	0.32
BIOCARTA BIOPEPTIDES PATHWAY	40	genes.ES.table	0.45	1.6	0.018	0.86	0.93	0.2	0.16	0.17	0.53	0.28
BIOCARTA INTEGRIN PATHWAY	38	genes.ES.table	0.54	1.9	0.0063	0.69	0.43	0.34	0.2	0.28	0	0.16
BIOCARTA MYOSIN PATHWAY	29	genes.ES.table	0.54	1.7	0.01	0.75	0.83	0.24	0.11	0.22	0.38	0.22
BIOCARTA RHO PATHWAY	32	genes.ES.table	0.49	1.8	0.011	0.63	0.67	0.34	0.17	0.28	0.24	0.16
SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES	35	genes.ES.table	0.5	1.6	0.033	0.77	0.93	0.4	0.17	0.33	0.48	0.24

genes ES table in pathway: KEGG LYSINE DEGRADATION

Table S11. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SLC2A4	SLC2A4	SLC2A4	563	0.56	0.12	YES
2	AKT3	AKT3	AKT3	1071	0.41	0.2	YES
3	SRC	SRC	SRC	1417	0.35	0.28	YES
4	RICTOR	RICTOR	RICTOR	2160	0.26	0.3	YES
5	CDKN1B	CDKN1B	CDKN1B	2973	0.19	0.31	YES
6	YWHAH	YWHAH	YWHAH	3121	0.18	0.35	YES
7	PDPK1	PDPK1	PDPK1	3904	0.14	0.34	YES
8	MAP3K5	MAP3K5	MAP3K5	3920	0.14	0.38	YES
9	FOXO1	FOXO1	FOXO1	4369	0.12	0.39	YES
10	FOXO4	FOXO4	FOXO4	4482	0.11	0.41	YES
11	KPNA1	KPNA1	KPNA1	4697	0.11	0.43	YES
12	GSK3B	GSK3B	GSK3B	4983	0.097	0.44	YES
13	PRKDC	PRKDC	PRKDC	5541	0.079	0.43	YES
14	PRKACA	PRKACA	PRKACA	5608	0.077	0.45	YES
15	CDKN1A	CDKN1A	CDKN1A	6033	0.065	0.44	NO
16	RAF1	RAF1	RAF1	6405	0.055	0.44	NO
17	YWHAZ	YWHAZ	YWHAZ	6632	0.048	0.44	NO
18	BAD	BAD	BAD	7465	0.027	0.4	NO
19	AKT1	AKT1	AKT1	7885	0.017	0.38	NO
20	YWHAQ	YWHAQ	YWHAQ	7967	0.015	0.38	NO
21	MAPKAP1	MAPKAP1	MAPKAP1	8468	0.0032	0.35	NO
22	GSK3A	GSK3A	GSK3A	8525	0.002	0.35	NO
23	MTOR	MTOR	MTOR	8911	-0.0068	0.33	NO
24	HSP90AA1	HSP90AA1	HSP90AA1	8940	-0.0074	0.33	NO
25	FOXO3	FOXO3	FOXO3	9240	-0.014	0.32	NO
26	SFN	SFN	SFN	9396	-0.018	0.32	NO
27	BCL2L1	BCL2L1	BCL2L1	9622	-0.023	0.31	NO
28	AKT2	AKT2	AKT2	9930	-0.03	0.3	NO
29	YWHAG	YWHAG	YWHAG	9938	-0.031	0.31	NO
30	YWHAB	YWHAB	YWHAB	10382	-0.042	0.3	NO
31	MLST8	MLST8	MLST8	10581	-0.047	0.3	NO
32	CHUK	CHUK	CHUK	11090	-0.06	0.29	NO
33	CASP9	CASP9	CASP9	12225	-0.09	0.25	NO
34	TBC1D4	TBC1D4	TBC1D4	13472	-0.13	0.21	NO
35	YWHAE	YWHAE	YWHAE	14391	-0.17	0.21	NO

Figure S21. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG LYSINE DEGRADATION.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSINE DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PROPANOATE METABOLISM

Table S12. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PPP1R12B	PPP1R12B	PPP1R12B	46	1.2	0.16	YES
2	ACTA1	ACTA1	ACTA1	347	0.67	0.24	YES
3	ACTN2	ACTN2	ACTN2	894	0.45	0.27	YES
4	TNS1	TNS1	TNS1	907	0.44	0.33	YES
5	ACTN1	ACTN1	ACTN1	934	0.44	0.39	YES
6	ITGA1	ITGA1	ITGA1	1142	0.4	0.43	YES
7	SRC	SRC	SRC	1417	0.35	0.47	YES
8	VCL	VCL	VCL	1604	0.32	0.5	YES
9	ROCK1	ROCK1	ROCK1	1971	0.27	0.52	YES
10	RAP1A	RAP1A	RAP1A	2471	0.23	0.52	YES
11	TLN1	TLN1	TLN1	2720	0.2	0.54	YES
12	CAV1	CAV1	CAV1	3233	0.17	0.54	YES
13	ZYX	ZYX	ZYX	3534	0.16	0.54	YES
14	ITGB1	ITGB1	ITGB1	4479	0.11	0.5	NO
15	PTK2	PTK2	PTK2	5514	0.08	0.46	NO
16	SOS1	SOS1	SOS1	5844	0.07	0.45	NO
17	RAF1	RAF1	RAF1	6405	0.055	0.43	NO
18	MAPK1	MAPK1	MAPK1	6710	0.046	0.42	NO
19	SHC1	SHC1	SHC1	7826	0.019	0.36	NO
20	MAP2K1	MAP2K1	MAP2K1	8866	-0.0056	0.3	NO
21	CAPN1	CAPN1	CAPN1	8967	-0.0079	0.3	NO
22	JUN	JUN	JUN	9506	-0.02	0.27	NO
23	RHOA	RHOA	RHOA	9612	-0.023	0.27	NO
24	MAPK8	MAPK8	MAPK8	9616	-0.023	0.27	NO
25	ACTN3	ACTN3	ACTN3	9792	-0.027	0.26	NO
26	CRKL	CRKL	CRKL	9828	-0.028	0.27	NO
27	HRAS	HRAS	HRAS	10251	-0.039	0.25	NO
28	RAPGEF1	RAPGEF1	RAPGEF1	10962	-0.056	0.22	NO
29	BCR	BCR	BCR	11150	-0.061	0.22	NO
30	BCAR1	BCAR1	BCAR1	11366	-0.067	0.21	NO
31	CAPNS1	CAPNS1	CAPNS1	11377	-0.067	0.22	NO
32	GRB2	GRB2	GRB2	11420	-0.068	0.23	NO
33	MAPK3	MAPK3	MAPK3	11468	-0.069	0.24	NO
34	MAP2K2	MAP2K2	MAP2K2	13213	-0.12	0.16	NO
35	PXN	PXN	PXN	14017	-0.15	0.13	NO
36	CSK	CSK	CSK	14278	-0.16	0.14	NO
37	CAPNS2	CAPNS2	CAPNS2	15366	-0.22	0.11	NO
38	FYN	FYN	FYN	16267	-0.3	0.1	NO

Figure S23. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PROPANOATE METABOLISM.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROPANOATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG BUTANOATE METABOLISM

Table S13. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH1B1	ALDH1B1	ALDH1B1	231	0.77	0.12	YES
2	SETMAR	SETMAR	SETMAR	621	0.54	0.19	YES
3	HADH	HADH	HADH	1430	0.35	0.21	YES
4	ALDH3A2	ALDH3A2	ALDH3A2	1723	0.31	0.25	YES
5	BBOX1	BBOX1	BBOX1	2295	0.24	0.26	YES
6	PIPOX	PIPOX	PIPOX	2468	0.23	0.29	YES
7	ACAT2	ACAT2	ACAT2	2596	0.22	0.32	YES
8	SETD1B	SETD1B	SETD1B	2854	0.2	0.34	YES
9	ACAT1	ACAT1	ACAT1	2913	0.19	0.37	YES
10	ASH1L	ASH1L	ASH1L	3055	0.18	0.39	YES
11	OGDHL	OGDHL	OGDHL	3640	0.15	0.39	YES
12	ALDH2	ALDH2	ALDH2	3798	0.14	0.4	YES
13	EHHADH	EHHADH	EHHADH	4203	0.13	0.4	YES
14	WHSC1	WHSC1	WHSC1	4375	0.12	0.42	YES
15	AADAT	AADAT	AADAT	4419	0.12	0.43	YES
16	SETD8	SETD8	SETD8	4426	0.12	0.45	YES
17	PLOD2	PLOD2	PLOD2	4952	0.098	0.44	YES
18	TMLHE	TMLHE	TMLHE	5065	0.095	0.45	YES
19	SETD2	SETD2	SETD2	5246	0.088	0.46	YES
20	SUV39H1	SUV39H1	SUV39H1	5268	0.088	0.47	YES
21	OGDH	OGDH	OGDH	5623	0.077	0.47	NO
22	WHSC1L1	WHSC1L1	WHSC1L1	5919	0.068	0.46	NO
23	DOT1L	DOT1L	DOT1L	5977	0.066	0.47	NO
24	SETD7	SETD7	SETD7	6844	0.042	0.43	NO
25	SETD1A	SETD1A	SETD1A	6891	0.041	0.43	NO
26	DLST	DLST	DLST	8266	0.0079	0.36	NO
27	SETDB1	SETDB1	SETDB1	8308	0.0068	0.36	NO
28	EHMT2	EHMT2	EHMT2	8793	-0.0041	0.33	NO
29	AASS	AASS	AASS	8851	-0.0054	0.33	NO
30	AASDH	AASDH	AASDH	9154	-0.012	0.32	NO
31	ALDH9A1	ALDH9A1	ALDH9A1	9208	-0.014	0.32	NO
32	EHMT1	EHMT1	EHMT1	9267	-0.015	0.32	NO
33	NSD1	NSD1	NSD1	9530	-0.021	0.3	NO
34	GCDH	GCDH	GCDH	9560	-0.022	0.31	NO
35	ALDH7A1	ALDH7A1	ALDH7A1	9634	-0.023	0.31	NO
36	AASDHPPT	AASDHPPT	AASDHPPT	10402	-0.042	0.27	NO
37	SUV420H2	SUV420H2	SUV420H2	10607	-0.048	0.27	NO
38	SUV420H1	SUV420H1	SUV420H1	10671	-0.049	0.27	NO
39	HADHA	HADHA	HADHA	11853	-0.08	0.22	NO
40	ECHS1	ECHS1	ECHS1	12502	-0.099	0.2	NO
41	SETDB2	SETDB2	SETDB2	13354	-0.13	0.18	NO
42	SUV39H2	SUV39H2	SUV39H2	13612	-0.14	0.19	NO
43	PLOD3	PLOD3	PLOD3	14206	-0.16	0.18	NO
44	PLOD1	PLOD1	PLOD1	15056	-0.2	0.17	NO

Figure S25. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG BUTANOATE METABOLISM.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG BUTANOATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION

Table S14. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH1B1	ALDH1B1	ALDH1B1	231	0.77	0.12	YES
2	ACSM1	ACSM1	ACSM1	470	0.6	0.21	YES
3	BDH1	BDH1	BDH1	715	0.51	0.28	YES
4	GAD1	GAD1	GAD1	918	0.44	0.34	YES
5	OXCT1	OXCT1	OXCT1	1042	0.41	0.41	YES
6	L2HGDH	L2HGDH	L2HGDH	1381	0.36	0.45	YES
7	HADH	HADH	HADH	1430	0.35	0.51	YES
8	ALDH3A2	ALDH3A2	ALDH3A2	1723	0.31	0.54	YES
9	AKR1B10	AKR1B10	AKR1B10	2129	0.26	0.57	YES
10	ACAT2	ACAT2	ACAT2	2596	0.22	0.58	YES
11	ACAT1	ACAT1	ACAT1	2913	0.19	0.59	YES
12	ACSM5	ACSM5	ACSM5	2949	0.19	0.62	YES
13	ACSM3	ACSM3	ACSM3	3772	0.14	0.6	YES
14	ALDH2	ALDH2	ALDH2	3798	0.14	0.63	YES
15	EHHADH	EHHADH	EHHADH	4203	0.13	0.62	YES
16	ACSM2A	ACSM2A	ACSM2A	4347	0.12	0.64	YES
17	ALDH5A1	ALDH5A1	ALDH5A1	5450	0.082	0.59	NO
18	PDHB	PDHB	PDHB	6346	0.056	0.55	NO
19	PDHA1	PDHA1	PDHA1	7032	0.038	0.52	NO
20	ACADS	ACADS	ACADS	7556	0.025	0.5	NO
21	ABAT	ABAT	ABAT	7904	0.016	0.48	NO
22	OXCT2	OXCT2	OXCT2	8570	0.001	0.44	NO
23	HMGCS1	HMGCS1	HMGCS1	9199	-0.014	0.41	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	9208	-0.014	0.41	NO
25	HMGCS2	HMGCS2	HMGCS2	9311	-0.016	0.41	NO
26	ALDH7A1	ALDH7A1	ALDH7A1	9634	-0.023	0.4	NO
27	HMGCL	HMGCL	HMGCL	10297	-0.04	0.37	NO
28	AACS	AACS	AACS	10657	-0.048	0.35	NO
29	HADHA	HADHA	HADHA	11853	-0.08	0.3	NO
30	ECHS1	ECHS1	ECHS1	12502	-0.099	0.28	NO
31	BDH2	BDH2	BDH2	14484	-0.17	0.2	NO

Figure S27. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG INSULIN SIGNALING PATHWAY

Table S15. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYLK	MYLK	MYLK	43	1.2	0.16	YES
2	PPP1R12B	PPP1R12B	PPP1R12B	46	1.2	0.32	YES
3	SRC	SRC	SRC	1417	0.35	0.29	YES
4	PIP5K1B	PIP5K1B	PIP5K1B	1426	0.35	0.34	YES
5	ARHGEF5	ARHGEF5	ARHGEF5	1450	0.34	0.38	YES
6	VCL	VCL	VCL	1604	0.32	0.42	YES
7	ARHGAP6	ARHGAP6	ARHGAP6	1840	0.29	0.45	YES
8	ROCK1	ROCK1	ROCK1	1971	0.27	0.48	YES
9	TLN1	TLN1	TLN1	2720	0.2	0.47	YES
10	GSN	GSN	GSN	2951	0.19	0.48	YES
11	ARHGAP1	ARHGAP1	ARHGAP1	3135	0.18	0.49	YES
12	ARHGAP5	ARHGAP5	ARHGAP5	4914	0.099	0.41	NO
13	OPHN1	OPHN1	OPHN1	5028	0.096	0.42	NO
14	ACTR3	ACTR3	ACTR3	5829	0.071	0.38	NO
15	PIP5K1A	PIP5K1A	PIP5K1A	6711	0.046	0.34	NO
16	ARPC5	ARPC5	ARPC5	6996	0.039	0.33	NO
17	DIAPH1	DIAPH1	DIAPH1	8693	-0.0018	0.24	NO
18	ARHGEF11	ARHGEF11	ARHGEF11	8786	-0.0039	0.23	NO
19	PFN1	PFN1	PFN1	9143	-0.012	0.21	NO
20	RHOA	RHOA	RHOA	9612	-0.023	0.19	NO
21	ARPC1A	ARPC1A	ARPC1A	9783	-0.027	0.19	NO
22	ARPC2	ARPC2	ARPC2	9915	-0.03	0.18	NO
23	ARPC4	ARPC4	ARPC4	10454	-0.044	0.16	NO
24	CFL1	CFL1	CFL1	11147	-0.061	0.13	NO
25	ACTR2	ACTR2	ACTR2	12357	-0.094	0.076	NO
26	ARHGEF1	ARHGEF1	ARHGEF1	12622	-0.1	0.075	NO
27	ARPC3	ARPC3	ARPC3	13175	-0.12	0.061	NO
28	ARPC1B	ARPC1B	ARPC1B	15820	-0.26	-0.049	NO
29	BAIAP2	BAIAP2	BAIAP2	15822	-0.26	-0.014	NO
30	ARHGAP4	ARHGAP4	ARHGAP4	15975	-0.27	0.015	NO
31	MYL2	MYL2	MYL2	16260	-0.3	0.04	NO
32	LIMK1	LIMK1	LIMK1	17569	-0.47	0.033	NO

Figure S29. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG INSULIN SIGNALING PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG INSULIN SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

Table S16. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH1B1	ALDH1B1	ALDH1B1	231	0.77	0.19	YES
2	ALDH3A2	ALDH3A2	ALDH3A2	1723	0.31	0.18	YES
3	ACACB	ACACB	ACACB	2100	0.26	0.23	YES
4	LDHAL6B	LDHAL6B	LDHAL6B	2254	0.25	0.29	YES
5	ACAT2	ACAT2	ACAT2	2596	0.22	0.33	YES
6	ALDH6A1	ALDH6A1	ALDH6A1	2878	0.2	0.36	YES
7	ACAT1	ACAT1	ACAT1	2913	0.19	0.41	YES
8	ALDH2	ALDH2	ALDH2	3798	0.14	0.4	YES
9	ACSS3	ACSS3	ACSS3	3978	0.14	0.42	YES
10	EHHADH	EHHADH	EHHADH	4203	0.13	0.44	YES
11	SUCLG2	SUCLG2	SUCLG2	4660	0.11	0.45	YES
12	ACACA	ACACA	ACACA	4855	0.1	0.46	YES
13	PCCB	PCCB	PCCB	4986	0.097	0.48	YES
14	PCCA	PCCA	PCCA	5143	0.092	0.5	YES
15	ACADM	ACADM	ACADM	5277	0.088	0.51	YES
16	HIBCH	HIBCH	HIBCH	5546	0.079	0.52	YES
17	LDHAL6A	LDHAL6A	LDHAL6A	5795	0.072	0.52	YES
18	ACSS2	ACSS2	ACSS2	6498	0.052	0.5	NO
19	MUT	MUT	MUT	7011	0.038	0.48	NO
20	LDHB	LDHB	LDHB	7085	0.036	0.49	NO
21	ABAT	ABAT	ABAT	7904	0.016	0.44	NO
22	SUCLA2	SUCLA2	SUCLA2	7996	0.014	0.44	NO
23	MLYCD	MLYCD	MLYCD	8053	0.013	0.44	NO
24	SUCLG1	SUCLG1	SUCLG1	8608	0.00022	0.41	NO
25	ALDH9A1	ALDH9A1	ALDH9A1	9208	-0.014	0.38	NO
26	LDHC	LDHC	LDHC	9525	-0.02	0.37	NO
27	ALDH7A1	ALDH7A1	ALDH7A1	9634	-0.023	0.37	NO
28	MCEE	MCEE	MCEE	11118	-0.06	0.31	NO
29	LDHA	LDHA	LDHA	11182	-0.062	0.32	NO
30	ACSS1	ACSS1	ACSS1	11621	-0.074	0.31	NO
31	HADHA	HADHA	HADHA	11853	-0.08	0.32	NO
32	ECHS1	ECHS1	ECHS1	12502	-0.099	0.31	NO

Figure S31. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA BIOPEPTIDES PATHWAY.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA BIOPEPTIDES PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA INTEGRIN PATHWAY

Table S17. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PPP1R14A	PPP1R14A	PPP1R14A	83	1	0.12	YES
2	MYL9	MYL9	MYL9	346	0.68	0.18	YES
3	LIMS2	LIMS2	LIMS2	453	0.61	0.24	YES
4	PPP1R14C	PPP1R14C	PPP1R14C	793	0.48	0.28	YES
5	TNS1	TNS1	TNS1	907	0.44	0.33	YES
6	ACTN1	ACTN1	ACTN1	934	0.44	0.38	YES
7	PPP1R12A	PPP1R12A	PPP1R12A	1242	0.38	0.4	YES
8	ILK	ILK	ILK	1921	0.28	0.4	YES
9	RICTOR	RICTOR	RICTOR	2160	0.26	0.42	YES
10	PARVA	PARVA	PARVA	3509	0.16	0.36	NO
11	ZYX	ZYX	ZYX	3534	0.16	0.38	NO
12	IQGAP1	IQGAP1	IQGAP1	3871	0.14	0.37	NO
13	GSK3B	GSK3B	GSK3B	4983	0.097	0.32	NO
14	ZEB1	ZEB1	ZEB1	6190	0.06	0.26	NO
15	LIMS1	LIMS1	LIMS1	6477	0.053	0.26	NO
16	CTNNB1	CTNNB1	CTNNB1	6679	0.047	0.25	NO
17	PARP1	PARP1	PARP1	6994	0.039	0.24	NO
18	XPO1	XPO1	XPO1	7378	0.03	0.22	NO
19	CREB1	CREB1	CREB1	7411	0.029	0.22	NO
20	ARHGEF7	ARHGEF7	ARHGEF7	7505	0.026	0.22	NO
21	ILKAP	ILKAP	ILKAP	7635	0.023	0.21	NO
22	RUVBL1	RUVBL1	RUVBL1	7710	0.022	0.21	NO
23	AKT1	AKT1	AKT1	7885	0.017	0.2	NO
24	AURKA	AURKA	AURKA	8044	0.013	0.2	NO
25	CKAP5	CKAP5	CKAP5	8431	0.004	0.18	NO
26	DIAPH1	DIAPH1	DIAPH1	8693	-0.0018	0.16	NO
27	HSP90AA1	HSP90AA1	HSP90AA1	8940	-0.0074	0.15	NO
28	NCK2	NCK2	NCK2	9165	-0.012	0.14	NO
29	JUN	JUN	JUN	9506	-0.02	0.12	NO
30	CDC37	CDC37	CDC37	10396	-0.042	0.078	NO
31	ARHGEF6	ARHGEF6	ARHGEF6	10540	-0.046	0.076	NO
32	RAC1	RAC1	RAC1	11337	-0.066	0.039	NO
33	RUVBL2	RUVBL2	RUVBL2	11418	-0.068	0.043	NO
34	TACC3	TACC3	TACC3	11421	-0.068	0.051	NO
35	GIT2	GIT2	GIT2	11757	-0.077	0.041	NO
36	ELMO2	ELMO2	ELMO2	12020	-0.084	0.036	NO
37	NACA	NACA	NACA	12123	-0.087	0.041	NO
38	CDC42	CDC42	CDC42	12835	-0.11	0.015	NO
39	PXN	PXN	PXN	14017	-0.15	-0.033	NO
40	RHOG	RHOG	RHOG	14356	-0.17	-0.032	NO
41	PPP1R14B	PPP1R14B	PPP1R14B	16018	-0.27	-0.092	NO
42	PARVG	PARVG	PARVG	17158	-0.39	-0.11	NO
43	PARVB	PARVB	PARVB	17226	-0.41	-0.065	NO
44	SNAI1	SNAI1	SNAI1	17405	-0.44	-0.024	NO
45	CCND1	CCND1	CCND1	17890	-0.57	0.015	NO

Figure S33. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA INTEGRIN PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA INTEGRIN PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA MYOSIN PATHWAY

Table S18. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYLK	MYLK	MYLK	43	1.2	0.19	YES
2	PPP1R12B	PPP1R12B	PPP1R12B	46	1.2	0.38	YES
3	ARHGEF4	ARHGEF4	ARHGEF4	1403	0.35	0.37	YES
4	ARHGEF5	ARHGEF5	ARHGEF5	1450	0.34	0.42	YES
5	ARHGEF17	ARHGEF17	ARHGEF17	1720	0.31	0.46	YES
6	ARHGEF9	ARHGEF9	ARHGEF9	1761	0.3	0.5	YES
7	ROCK1	ROCK1	ROCK1	1971	0.27	0.54	YES
8	PLCB1	PLCB1	PLCB1	3145	0.18	0.5	NO
9	ARHGEF10	ARHGEF10	ARHGEF10	3757	0.14	0.49	NO
10	ARHGEF12	ARHGEF12	ARHGEF12	4601	0.11	0.46	NO
11	GNAQ	GNAQ	GNAQ	4704	0.11	0.48	NO
12	ARHGAP5	ARHGAP5	ARHGAP5	4914	0.099	0.48	NO
13	PKN1	PKN1	PKN1	5878	0.069	0.44	NO
14	GNA13	GNA13	GNA13	5896	0.068	0.45	NO
15	ARHGEF3	ARHGEF3	ARHGEF3	6658	0.048	0.42	NO
16	ARHGEF7	ARHGEF7	ARHGEF7	7505	0.026	0.37	NO
17	GNA12	GNA12	GNA12	7568	0.025	0.37	NO
18	ARHGEF2	ARHGEF2	ARHGEF2	8094	0.012	0.35	NO
19	ARHGEF18	ARHGEF18	ARHGEF18	8278	0.0077	0.34	NO
20	ARHGEF11	ARHGEF11	ARHGEF11	8786	-0.0039	0.31	NO
21	ARHGEF16	ARHGEF16	ARHGEF16	8952	-0.0076	0.3	NO
22	PRKCB	PRKCB	PRKCB	9591	-0.022	0.27	NO
23	ARHGEF6	ARHGEF6	ARHGEF6	10540	-0.046	0.23	NO
24	PRKCA	PRKCA	PRKCA	12524	-0.1	0.13	NO
25	ARHGEF1	ARHGEF1	ARHGEF1	12622	-0.1	0.15	NO
26	ARHGEF15	ARHGEF15	ARHGEF15	12941	-0.11	0.15	NO
27	GNB1	GNB1	GNB1	13349	-0.13	0.14	NO
28	MYL2	MYL2	MYL2	16260	-0.3	0.034	NO
29	ARHGEF19	ARHGEF19	ARHGEF19	17367	-0.43	0.044	NO

Figure S35. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA MYOSIN PATHWAY.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MYOSIN PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA RHO PATHWAY

Table S19. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ADHFE1	ADHFE1	ADHFE1	148	0.88	0.15	YES
2	PDK3	PDK3	PDK3	666	0.52	0.22	YES
3	L2HGDH	L2HGDH	L2HGDH	1381	0.36	0.24	YES
4	PDK4	PDK4	PDK4	2102	0.26	0.25	YES
5	IDH2	IDH2	IDH2	2121	0.26	0.3	YES
6	PDK1	PDK1	PDK1	2446	0.23	0.32	YES
7	NNT	NNT	NNT	2728	0.2	0.34	YES
8	IDH3A	IDH3A	IDH3A	3341	0.17	0.34	YES
9	SLC16A1	SLC16A1	SLC16A1	3750	0.14	0.34	YES
10	PDHX	PDHX	PDHX	3848	0.14	0.36	YES
11	PDPR	PDPR	PDPR	3877	0.14	0.39	YES
12	PDK2	PDK2	PDK2	4114	0.13	0.4	YES
13	PDP2	PDP2	PDP2	4305	0.12	0.41	YES
14	FH	FH	FH	4386	0.12	0.43	YES
15	SUCLG2	SUCLG2	SUCLG2	4660	0.11	0.43	YES
16	SLC16A8	SLC16A8	SLC16A8	4926	0.099	0.44	YES
17	DLAT	DLAT	DLAT	5013	0.096	0.45	YES
18	ACO2	ACO2	ACO2	5577	0.078	0.43	NO
19	OGDH	OGDH	OGDH	5623	0.077	0.44	NO
20	SDHA	SDHA	SDHA	5971	0.066	0.44	NO
21	SDHD	SDHD	SDHD	6197	0.06	0.44	NO
22	PDHB	PDHB	PDHB	6346	0.056	0.44	NO
23	DLD	DLD	DLD	6383	0.056	0.44	NO
24	CS	CS	CS	7022	0.038	0.42	NO
25	PDHA1	PDHA1	PDHA1	7032	0.038	0.42	NO
26	LDHB	LDHB	LDHB	7085	0.036	0.43	NO
27	SUCLA2	SUCLA2	SUCLA2	7996	0.014	0.38	NO
28	DLST	DLST	DLST	8266	0.0079	0.37	NO
29	SUCLG1	SUCLG1	SUCLG1	8608	0.00022	0.35	NO
30	SDHC	SDHC	SDHC	9038	-0.0095	0.32	NO
31	IDH3B	IDH3B	IDH3B	9394	-0.018	0.31	NO
32	D2HGDH	D2HGDH	D2HGDH	10228	-0.038	0.27	NO
33	SDHB	SDHB	SDHB	10820	-0.052	0.25	NO
34	MDH2	MDH2	MDH2	10938	-0.056	0.25	NO
35	BSG	BSG	BSG	11160	-0.062	0.25	NO
36	LDHA	LDHA	LDHA	11182	-0.062	0.26	NO
37	IDH3G	IDH3G	IDH3G	11470	-0.069	0.26	NO
38	PDP1	PDP1	PDP1	12518	-0.099	0.22	NO
39	SLC16A3	SLC16A3	SLC16A3	15831	-0.26	0.081	NO
40	IDH1	IDH1	IDH1	15877	-0.26	0.13	NO

Figure S37. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA RHO PATHWAY.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA RHO PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES

Table S20. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYH11	MYH11	MYH11	3	1.6	0.05	YES
2	KCNMB1	KCNMB1	KCNMB1	6	1.6	0.1	YES
3	ACTG2	ACTG2	ACTG2	31	1.2	0.14	YES
4	RAMP1	RAMP1	RAMP1	37	1.2	0.18	YES
5	MYLK	MYLK	MYLK	43	1.2	0.21	YES
6	PPP1R12B	PPP1R12B	PPP1R12B	46	1.2	0.25	YES
7	MRVI1	MRVI1	MRVI1	51	1.1	0.28	YES
8	PPP1R14A	PPP1R14A	PPP1R14A	83	1	0.31	YES
9	ADRA1A	ADRA1A	ADRA1A	129	0.91	0.34	YES
10	ADCY5	ADCY5	ADCY5	130	0.91	0.37	YES
11	ITPR1	ITPR1	ITPR1	188	0.81	0.39	YES
12	CACNA1C	CACNA1C	CACNA1C	279	0.73	0.41	YES
13	ACTA2	ACTA2	ACTA2	283	0.72	0.43	YES
14	KCNMA1	KCNMA1	KCNMA1	319	0.7	0.45	YES
15	MYL9	MYL9	MYL9	346	0.68	0.47	YES
16	PLA2G10	PLA2G10	PLA2G10	612	0.54	0.47	YES
17	PLCB4	PLCB4	PLCB4	686	0.52	0.49	YES
18	ADCY2	ADCY2	ADCY2	814	0.47	0.49	YES
19	PRKG1	PRKG1	PRKG1	951	0.43	0.5	YES
20	EDNRA	EDNRA	EDNRA	1024	0.42	0.51	YES
21	CALD1	CALD1	CALD1	1185	0.39	0.51	YES
22	PPP1R12A	PPP1R12A	PPP1R12A	1242	0.38	0.52	YES
23	GNA11	GNA11	GNA11	1634	0.32	0.51	NO
24	ROCK2	ROCK2	ROCK2	1810	0.3	0.51	NO
25	ROCK1	ROCK1	ROCK1	1971	0.27	0.51	NO
26	ADCY9	ADCY9	ADCY9	2723	0.2	0.47	NO
27	NPR1	NPR1	NPR1	2757	0.2	0.48	NO
28	PRKCG	PRKCG	PRKCG	2881	0.2	0.48	NO
29	CACNA1D	CACNA1D	CACNA1D	2903	0.19	0.48	NO
30	PPP1CB	PPP1CB	PPP1CB	3098	0.18	0.48	NO
31	PLCB1	PLCB1	PLCB1	3145	0.18	0.48	NO
32	MYLK3	MYLK3	MYLK3	3270	0.17	0.48	NO
33	PLA2G6	PLA2G6	PLA2G6	3333	0.17	0.48	NO
34	MYL6	MYL6	MYL6	3427	0.16	0.48	NO
35	PLA2G3	PLA2G3	PLA2G3	3511	0.16	0.48	NO
36	NPR2	NPR2	NPR2	3581	0.15	0.48	NO
37	ADCY6	ADCY6	ADCY6	3637	0.15	0.48	NO
38	PRKACB	PRKACB	PRKACB	3662	0.15	0.49	NO
39	PLA2G12A	PLA2G12A	PLA2G12A	3769	0.14	0.49	NO
40	PRKACG	PRKACG	PRKACG	3865	0.14	0.49	NO
41	GUCY1A3	GUCY1A3	GUCY1A3	4308	0.12	0.46	NO
42	ARHGEF12	ARHGEF12	ARHGEF12	4601	0.11	0.45	NO
43	GNAQ	GNAQ	GNAQ	4704	0.11	0.45	NO
44	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	4796	0.1	0.45	NO
45	PLCB3	PLCB3	PLCB3	4938	0.098	0.44	NO
46	CALM1	CALM1	CALM1	5273	0.088	0.43	NO
47	PRKACA	PRKACA	PRKACA	5608	0.077	0.41	NO
48	RAMP3	RAMP3	RAMP3	5734	0.073	0.41	NO
49	GNA13	GNA13	GNA13	5896	0.068	0.4	NO
50	BRAF	BRAF	BRAF	6220	0.06	0.38	NO
51	RAF1	RAF1	RAF1	6405	0.055	0.38	NO
52	MAPK1	MAPK1	MAPK1	6710	0.046	0.36	NO
53	ADCY8	ADCY8	ADCY8	7151	0.035	0.34	NO
54	GNA12	GNA12	GNA12	7568	0.025	0.32	NO
55	PRKCD	PRKCD	PRKCD	7779	0.02	0.3	NO
56	ADCY3	ADCY3	ADCY3	7984	0.015	0.29	NO
57	KCNMB3	KCNMB3	KCNMB3	8131	0.011	0.28	NO
58	ADCY1	ADCY1	ADCY1	8194	0.0096	0.28	NO
59	CALCRL	CALCRL	CALCRL	8328	0.0064	0.28	NO
60	ARHGEF11	ARHGEF11	ARHGEF11	8786	-0.0039	0.25	NO
61	MAP2K1	MAP2K1	MAP2K1	8866	-0.0056	0.25	NO
62	CALM3	CALM3	CALM3	8927	-0.0071	0.24	NO
63	CALML3	CALML3	CALML3	8996	-0.0085	0.24	NO
64	GUCY1B3	GUCY1B3	GUCY1B3	9347	-0.017	0.22	NO
65	PRKCB	PRKCB	PRKCB	9591	-0.022	0.21	NO
66	RHOA	RHOA	RHOA	9612	-0.023	0.21	NO
67	ARAF	ARAF	ARAF	9773	-0.027	0.2	NO
68	PPP1CC	PPP1CC	PPP1CC	10309	-0.04	0.17	NO
69	CALM2	CALM2	CALM2	10425	-0.043	0.17	NO
70	GNAS	GNAS	GNAS	10474	-0.044	0.16	NO
71	ADRA1D	ADRA1D	ADRA1D	10551	-0.046	0.16	NO
72	CACNA1F	CACNA1F	CACNA1F	11331	-0.066	0.12	NO
73	MAPK3	MAPK3	MAPK3	11468	-0.069	0.12	NO
74	PRKCA	PRKCA	PRKCA	12524	-0.1	0.06	NO
75	ARHGEF1	ARHGEF1	ARHGEF1	12622	-0.1	0.058	NO
76	MAP2K2	MAP2K2	MAP2K2	13213	-0.12	0.029	NO
77	PRKCQ	PRKCQ	PRKCQ	13244	-0.12	0.031	NO
78	MYL6B	MYL6B	MYL6B	13605	-0.14	0.016	NO
79	PLA2G12B	PLA2G12B	PLA2G12B	13661	-0.14	0.017	NO
80	PLA2G2D	PLA2G2D	PLA2G2D	13710	-0.14	0.018	NO
81	PRKCH	PRKCH	PRKCH	13800	-0.14	0.018	NO
82	ADORA2A	ADORA2A	ADORA2A	13893	-0.15	0.018	NO
83	PPP1CA	PPP1CA	PPP1CA	13944	-0.15	0.019	NO
84	RAMP2	RAMP2	RAMP2	14034	-0.15	0.019	NO
85	ITPR2	ITPR2	ITPR2	14085	-0.15	0.021	NO
86	CALML6	CALML6	CALML6	14105	-0.16	0.025	NO
87	PRKCE	PRKCE	PRKCE	14241	-0.16	0.023	NO
88	ADCY4	ADCY4	ADCY4	14319	-0.16	0.024	NO
89	GUCY1A2	GUCY1A2	GUCY1A2	14475	-0.17	0.021	NO
90	ITPR3	ITPR3	ITPR3	14829	-0.19	0.007	NO
91	CACNA1S	CACNA1S	CACNA1S	14990	-0.2	0.0044	NO
92	CYP4A11	CYP4A11	CYP4A11	14993	-0.2	0.011	NO
93	PLA2G5	PLA2G5	PLA2G5	15091	-0.2	0.012	NO
94	AVPR1A	AVPR1A	AVPR1A	15359	-0.22	0.0039	NO
95	PRKX	PRKX	PRKX	15418	-0.23	0.0078	NO
96	ADRA1B	ADRA1B	ADRA1B	15470	-0.23	0.012	NO
97	PLA2G4A	PLA2G4A	PLA2G4A	15786	-0.25	0.0028	NO
98	PTGIR	PTGIR	PTGIR	15921	-0.26	0.0037	NO
99	PLA2G1B	PLA2G1B	PLA2G1B	15928	-0.26	0.012	NO
100	AGTR1	AGTR1	AGTR1	16331	-0.3	-0.00094	NO
101	MYLK2	MYLK2	MYLK2	16554	-0.32	-0.003	NO
102	ADCY7	ADCY7	ADCY7	16570	-0.32	0.0064	NO
103	ADORA2B	ADORA2B	ADORA2B	16671	-0.34	0.012	NO
104	PLCB2	PLCB2	PLCB2	17165	-0.4	-0.0033	NO
105	KCNMB2	KCNMB2	KCNMB2	17611	-0.48	-0.013	NO
106	PLA2G2A	PLA2G2A	PLA2G2A	17957	-0.61	-0.013	NO
107	KCNMB4	KCNMB4	KCNMB4	18105	-0.78	0.0035	NO

Figure S39. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Subtype clus3 enriched pathways

Table 5. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus3. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE	26	genes.ES.table	0.6	1.6	0.012	0.42	0.92	0.46	0.18	0.38	0.22	0.1
KEGG WNT SIGNALING PATHWAY	147	genes.ES.table	0.51	1.8	0.006	0.53	0.62	0.24	0.13	0.21	0.19	0.12
KEGG AXON GUIDANCE	129	genes.ES.table	0.53	1.7	0.002	0.5	0.87	0.54	0.29	0.39	0.26	0.13
KEGG BASAL CELL CARCINOMA	53	genes.ES.table	0.67	1.7	0.004	0.63	0.83	0.47	0.13	0.41	0.29	0.16
BIOCARTA WNT PATHWAY	26	genes.ES.table	0.59	1.9	0.0085	0.45	0.32	0.23	0.12	0.2	0	0.11
WNT SIGNALING	85	genes.ES.table	0.56	1.8	0.006	0.59	0.59	0.35	0.17	0.29	0.21	0.14
ST WNT BETA CATENIN PATHWAY	32	genes.ES.table	0.61	1.8	0.0061	0.77	0.59	0.28	0.11	0.25	0.27	0.18
PID NOTCH PATHWAY	58	genes.ES.table	0.51	1.7	0.0083	0.41	0.89	0.33	0.22	0.26	0.21	0.097
PID PS1PATHWAY	46	genes.ES.table	0.6	2	0	0.42	0.17	0.28	0.16	0.24	0	0.096
PID WNT SIGNALING PATHWAY	28	genes.ES.table	0.69	1.7	0.012	0.48	0.88	0.57	0.17	0.48	0.24	0.12

genes ES table in pathway: KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE

Table S21. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SSPO	SSPO	SSPO	45	0.68	0.11	YES
2	WIF1	WIF1	WIF1	138	0.57	0.2	YES
3	DTX1	DTX1	DTX1	326	0.49	0.28	YES
4	DLL1	DLL1	DLL1	683	0.4	0.32	YES
5	NKD1	NKD1	NKD1	768	0.38	0.38	YES
6	TLE1	TLE1	TLE1	1281	0.31	0.41	YES
7	DKK2	DKK2	DKK2	1553	0.28	0.44	YES
8	HNF1A	HNF1A	HNF1A	1667	0.26	0.48	YES
9	LRP6	LRP6	LRP6	1683	0.26	0.52	YES
10	CCND1	CCND1	CCND1	1851	0.25	0.56	YES
11	FZD1	FZD1	FZD1	2084	0.23	0.58	YES
12	FOS	FOS	FOS	2735	0.18	0.58	YES
13	KREMEN2	KREMEN2	KREMEN2	2910	0.17	0.6	YES
14	NOTCH1	NOTCH1	NOTCH1	4011	0.13	0.56	NO
15	CSNK2A1	CSNK2A1	CSNK2A1	4995	0.097	0.52	NO
16	APH1A	APH1A	APH1A	5090	0.094	0.53	NO
17	APC	APC	APC	5142	0.093	0.54	NO
18	MAP3K7	MAP3K7	MAP3K7	5517	0.083	0.54	NO
19	PPARD	PPARD	PPARD	5744	0.078	0.54	NO
20	HDAC1	HDAC1	HDAC1	6407	0.065	0.51	NO
21	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.52	NO
22	JUN	JUN	JUN	7420	0.046	0.48	NO
23	DVL1	DVL1	DVL1	7494	0.045	0.48	NO
24	CTBP1	CTBP1	CTBP1	7723	0.041	0.47	NO
25	FBXW11	FBXW11	FBXW11	7903	0.039	0.47	NO
26	APH1B	APH1B	APH1B	7921	0.038	0.48	NO
27	CREBBP	CREBBP	CREBBP	8040	0.036	0.48	NO
28	ADAM10	ADAM10	ADAM10	8144	0.035	0.48	NO
29	PSEN1	PSEN1	PSEN1	8667	0.027	0.45	NO
30	MYC	MYC	MYC	8716	0.026	0.45	NO
31	PPP2R5D	PPP2R5D	PPP2R5D	8721	0.026	0.46	NO
32	WNT1	WNT1	WNT1	9871	0.0084	0.39	NO
33	NLK	NLK	NLK	10341	0.00097	0.37	NO
34	NCSTN	NCSTN	NCSTN	10412	0.000046	0.36	NO
35	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.35	NO
36	FRAT1	FRAT1	FRAT1	11400	-0.015	0.31	NO
37	AXIN1	AXIN1	AXIN1	11506	-0.017	0.31	NO
38	TAB1	TAB1	TAB1	11631	-0.019	0.31	NO
39	NEDD4	NEDD4	NEDD4	11778	-0.021	0.3	NO
40	MAPK1	MAPK1	MAPK1	12006	-0.026	0.3	NO
41	CSNK1A1	CSNK1A1	CSNK1A1	12073	-0.027	0.3	NO
42	PSENEN	PSENEN	PSENEN	12203	-0.029	0.29	NO
43	AES	AES	AES	12396	-0.033	0.29	NO
44	MAPK3	MAPK3	MAPK3	12593	-0.036	0.28	NO
45	RBPJ	RBPJ	RBPJ	13553	-0.057	0.24	NO
46	DKK1	DKK1	DKK1	14533	-0.085	0.2	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG WNT SIGNALING PATHWAY

Table S22. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	WIF1	WIF1	WIF1	138	0.57	0.2	YES
2	LEF1	LEF1	LEF1	622	0.41	0.32	YES
3	TLE1	TLE1	TLE1	1281	0.31	0.4	YES
4	CCND1	CCND1	CCND1	1851	0.25	0.46	YES
5	FZD1	FZD1	FZD1	2084	0.23	0.52	YES
6	BTRC	BTRC	BTRC	2241	0.22	0.59	YES
7	CSNK2A1	CSNK2A1	CSNK2A1	4995	0.097	0.48	NO
8	APC	APC	APC	5142	0.093	0.5	NO
9	MAP3K7	MAP3K7	MAP3K7	5517	0.083	0.51	NO
10	PPARD	PPARD	PPARD	5744	0.078	0.53	NO
11	HDAC1	HDAC1	HDAC1	6407	0.065	0.52	NO
12	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.53	NO
13	DVL1	DVL1	DVL1	7494	0.045	0.5	NO
14	CTBP1	CTBP1	CTBP1	7723	0.041	0.5	NO
15	CSNK1D	CSNK1D	CSNK1D	7959	0.038	0.5	NO
16	CREBBP	CREBBP	CREBBP	8040	0.036	0.51	NO
17	MYC	MYC	MYC	8716	0.026	0.48	NO
18	WNT1	WNT1	WNT1	9871	0.0084	0.42	NO
19	SMAD4	SMAD4	SMAD4	10283	0.0018	0.4	NO
20	NLK	NLK	NLK	10341	0.00097	0.39	NO
21	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.38	NO
22	FRAT1	FRAT1	FRAT1	11400	-0.015	0.34	NO
23	AXIN1	AXIN1	AXIN1	11506	-0.017	0.34	NO
24	TAB1	TAB1	TAB1	11631	-0.019	0.34	NO
25	PPP2CA	PPP2CA	PPP2CA	11774	-0.021	0.34	NO
26	CSNK1A1	CSNK1A1	CSNK1A1	12073	-0.027	0.34	NO

Figure S43. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG WNT SIGNALING PATHWAY.

Figure S44. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG WNT SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG AXON GUIDANCE

Table S23. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NKD2	NKD2	NKD2	18	0.76	0.14	YES
2	WIF1	WIF1	WIF1	138	0.57	0.25	YES
3	CXXC4	CXXC4	CXXC4	314	0.49	0.33	YES
4	DACT1	DACT1	DACT1	417	0.46	0.42	YES
5	NKD1	NKD1	NKD1	768	0.38	0.47	YES
6	ANKRD6	ANKRD6	ANKRD6	1443	0.29	0.49	YES
7	DKK2	DKK2	DKK2	1553	0.28	0.54	YES
8	SFRP1	SFRP1	SFRP1	1733	0.26	0.58	YES
9	CER1	CER1	CER1	1990	0.24	0.61	YES
10	DKK3	DKK3	DKK3	2799	0.18	0.6	NO
11	AXIN2	AXIN2	AXIN2	4796	0.1	0.51	NO
12	SENP2	SENP2	SENP2	4970	0.098	0.52	NO
13	LRP1	LRP1	LRP1	5104	0.094	0.53	NO
14	APC	APC	APC	5142	0.093	0.54	NO
15	PTPRA	PTPRA	PTPRA	5394	0.086	0.55	NO
16	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.5	NO
17	AKT2	AKT2	AKT2	6997	0.054	0.48	NO
18	DVL1	DVL1	DVL1	7494	0.045	0.46	NO
19	PSEN1	PSEN1	PSEN1	8667	0.027	0.4	NO
20	RPSA	RPSA	RPSA	9074	0.02	0.38	NO
21	GSK3A	GSK3A	GSK3A	10250	0.0023	0.32	NO
22	AKT1	AKT1	AKT1	10511	-0.0015	0.3	NO
23	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.3	NO
24	FRAT1	FRAT1	FRAT1	11400	-0.015	0.26	NO
25	AXIN1	AXIN1	AXIN1	11506	-0.017	0.26	NO
26	CSNK1A1	CSNK1A1	CSNK1A1	12073	-0.027	0.23	NO
27	FSTL1	FSTL1	FSTL1	12558	-0.036	0.21	NO
28	CBY1	CBY1	CBY1	13847	-0.064	0.15	NO
29	AKT3	AKT3	AKT3	14240	-0.075	0.15	NO
30	PIN1	PIN1	PIN1	14492	-0.084	0.15	NO
31	DKK1	DKK1	DKK1	14533	-0.085	0.16	NO
32	MVP	MVP	MVP	16593	-0.2	0.087	NO

Figure S45. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG AXON GUIDANCE.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AXON GUIDANCE, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG BASAL CELL CARCINOMA

Table S24. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CCND2	CCND2	CCND2	103	0.6	0.041	YES
2	WIF1	WIF1	WIF1	138	0.57	0.083	YES
3	WNT5A	WNT5A	WNT5A	183	0.55	0.12	YES
4	CXXC4	CXXC4	CXXC4	314	0.49	0.15	YES
5	FZD2	FZD2	FZD2	554	0.43	0.17	YES
6	FZD3	FZD3	FZD3	606	0.41	0.2	YES
7	LEF1	LEF1	LEF1	622	0.41	0.23	YES
8	WNT11	WNT11	WNT11	739	0.38	0.25	YES
9	NKD1	NKD1	NKD1	768	0.38	0.28	YES
10	FZD8	FZD8	FZD8	862	0.36	0.3	YES
11	WNT4	WNT4	WNT4	1034	0.34	0.32	YES
12	WNT3A	WNT3A	WNT3A	1136	0.32	0.34	YES
13	WNT6	WNT6	WNT6	1174	0.32	0.36	YES
14	LRP5	LRP5	LRP5	1194	0.32	0.38	YES
15	TLE1	TLE1	TLE1	1281	0.31	0.4	YES
16	WNT5B	WNT5B	WNT5B	1467	0.28	0.42	YES
17	WNT7A	WNT7A	WNT7A	1585	0.27	0.43	YES
18	LRP6	LRP6	LRP6	1683	0.26	0.44	YES
19	WNT7B	WNT7B	WNT7B	1702	0.26	0.46	YES
20	SFRP1	SFRP1	SFRP1	1733	0.26	0.48	YES
21	CCND1	CCND1	CCND1	1851	0.25	0.49	YES
22	BCL9	BCL9	BCL9	1912	0.24	0.51	YES
23	FZD1	FZD1	FZD1	2084	0.23	0.52	YES
24	BTRC	BTRC	BTRC	2241	0.22	0.52	YES
25	PYGO1	PYGO1	PYGO1	2277	0.21	0.54	YES
26	PITX2	PITX2	PITX2	2743	0.18	0.53	YES
27	FRZB	FRZB	FRZB	2832	0.18	0.54	YES
28	RHOU	RHOU	RHOU	2834	0.18	0.55	YES
29	CTNNBIP1	CTNNBIP1	CTNNBIP1	2974	0.17	0.56	YES
30	WNT3	WNT3	WNT3	3088	0.17	0.56	YES
31	WNT16	WNT16	WNT16	3521	0.15	0.55	NO
32	TCF7L1	TCF7L1	TCF7L1	3522	0.15	0.56	NO
33	TLE2	TLE2	TLE2	4263	0.12	0.53	NO
34	FZD4	FZD4	FZD4	4392	0.12	0.53	NO
35	FZD7	FZD7	FZD7	4559	0.11	0.53	NO
36	SENP2	SENP2	SENP2	4970	0.098	0.51	NO
37	CSNK2A1	CSNK2A1	CSNK2A1	4995	0.097	0.52	NO
38	APC	APC	APC	5142	0.093	0.52	NO
39	WNT10A	WNT10A	WNT10A	5438	0.085	0.51	NO
40	CTBP2	CTBP2	CTBP2	5712	0.079	0.5	NO
41	WNT9A	WNT9A	WNT9A	6082	0.071	0.48	NO
42	RPL13A	RPL13A	RPL13A	6090	0.071	0.49	NO
43	DVL2	DVL2	DVL2	6239	0.068	0.49	NO
44	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.48	NO
45	EP300	EP300	EP300	6879	0.056	0.46	NO
46	JUN	JUN	JUN	7420	0.046	0.44	NO
47	DVL1	DVL1	DVL1	7494	0.045	0.43	NO
48	CTBP1	CTBP1	CTBP1	7723	0.041	0.42	NO
49	CCND3	CCND3	CCND3	7789	0.04	0.42	NO
50	PPP2R1A	PPP2R1A	PPP2R1A	7808	0.04	0.43	NO
51	FBXW11	FBXW11	FBXW11	7903	0.039	0.42	NO
52	CSNK1D	CSNK1D	CSNK1D	7959	0.038	0.42	NO
53	CSNK1G1	CSNK1G1	CSNK1G1	8509	0.029	0.4	NO
54	MYC	MYC	MYC	8716	0.026	0.39	NO
55	FBXW4	FBXW4	FBXW4	8884	0.023	0.38	NO
56	FZD5	FZD5	FZD5	8973	0.022	0.38	NO
57	TCF7	TCF7	TCF7	9174	0.019	0.37	NO
58	WISP1	WISP1	WISP1	9368	0.016	0.36	NO
59	WNT1	WNT1	WNT1	9871	0.0084	0.33	NO
60	GSK3A	GSK3A	GSK3A	10250	0.0023	0.31	NO
61	NLK	NLK	NLK	10341	0.00097	0.3	NO
62	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.29	NO
63	T	T	T	10775	-0.0056	0.28	NO
64	FBXW2	FBXW2	FBXW2	11071	-0.01	0.26	NO
65	FRAT1	FRAT1	FRAT1	11400	-0.015	0.25	NO
66	AXIN1	AXIN1	AXIN1	11506	-0.017	0.24	NO
67	PPP2CA	PPP2CA	PPP2CA	11774	-0.021	0.23	NO
68	KREMEN1	KREMEN1	KREMEN1	11969	-0.025	0.22	NO
69	CSNK1A1	CSNK1A1	CSNK1A1	12073	-0.027	0.22	NO
70	WNT2B	WNT2B	WNT2B	12142	-0.028	0.22	NO
71	AES	AES	AES	12396	-0.033	0.2	NO
72	GAPDH	GAPDH	GAPDH	13525	-0.056	0.15	NO
73	SLC9A3R1	SLC9A3R1	SLC9A3R1	13820	-0.064	0.14	NO
74	HPRT1	HPRT1	HPRT1	13999	-0.068	0.13	NO
75	DAAM1	DAAM1	DAAM1	14211	-0.074	0.12	NO
76	DKK1	DKK1	DKK1	14533	-0.085	0.11	NO
77	PORCN	PORCN	PORCN	14636	-0.088	0.12	NO
78	DIXDC1	DIXDC1	DIXDC1	14672	-0.089	0.12	NO
79	SOX17	SOX17	SOX17	14769	-0.094	0.12	NO
80	WNT2	WNT2	WNT2	14930	-0.099	0.12	NO
81	ACTB	ACTB	ACTB	15239	-0.11	0.11	NO
82	SFRP4	SFRP4	SFRP4	15255	-0.11	0.12	NO
83	FOSL1	FOSL1	FOSL1	15750	-0.14	0.1	NO
84	B2M	B2M	B2M	16515	-0.19	0.075	NO
85	FZD6	FZD6	FZD6	16736	-0.21	0.079	NO

Figure S47. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG BASAL CELL CARCINOMA.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG BASAL CELL CARCINOMA, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA WNT PATHWAY

Table S25. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NKD2	NKD2	NKD2	18	0.76	0.033	YES
2	SFRP5	SFRP5	SFRP5	24	0.73	0.066	YES
3	VANGL2	VANGL2	VANGL2	72	0.64	0.093	YES
4	CCND2	CCND2	CCND2	103	0.6	0.12	YES
5	APC2	APC2	APC2	116	0.59	0.14	YES
6	FZD10	FZD10	FZD10	117	0.59	0.17	YES
7	WIF1	WIF1	WIF1	138	0.57	0.2	YES
8	WNT5A	WNT5A	WNT5A	183	0.55	0.22	YES
9	FZD9	FZD9	FZD9	240	0.52	0.24	YES
10	CXXC4	CXXC4	CXXC4	314	0.49	0.26	YES
11	PRICKLE1	PRICKLE1	PRICKLE1	370	0.48	0.28	YES
12	FZD2	FZD2	FZD2	554	0.43	0.29	YES
13	FZD3	FZD3	FZD3	606	0.41	0.3	YES
14	LEF1	LEF1	LEF1	622	0.41	0.32	YES
15	WNT11	WNT11	WNT11	739	0.38	0.33	YES
16	NKD1	NKD1	NKD1	768	0.38	0.35	YES
17	FZD8	FZD8	FZD8	862	0.36	0.36	YES
18	DAAM2	DAAM2	DAAM2	869	0.36	0.37	YES
19	RAC3	RAC3	RAC3	902	0.36	0.39	YES
20	CAMK2B	CAMK2B	CAMK2B	1022	0.34	0.4	YES
21	WNT4	WNT4	WNT4	1034	0.34	0.41	YES
22	WNT3A	WNT3A	WNT3A	1136	0.32	0.42	YES
23	WNT6	WNT6	WNT6	1174	0.32	0.43	YES
24	LRP5	LRP5	LRP5	1194	0.32	0.45	YES
25	WNT5B	WNT5B	WNT5B	1467	0.28	0.44	YES
26	DKK2	DKK2	DKK2	1553	0.28	0.45	YES
27	WNT7A	WNT7A	WNT7A	1585	0.27	0.46	YES
28	LRP6	LRP6	LRP6	1683	0.26	0.47	YES
29	WNT7B	WNT7B	WNT7B	1702	0.26	0.48	YES
30	SFRP1	SFRP1	SFRP1	1733	0.26	0.49	YES
31	CCND1	CCND1	CCND1	1851	0.25	0.5	YES
32	CER1	CER1	CER1	1990	0.24	0.5	YES
33	FZD1	FZD1	FZD1	2084	0.23	0.5	YES
34	BTRC	BTRC	BTRC	2241	0.22	0.5	YES
35	TP53	TP53	TP53	2354	0.21	0.51	YES
36	CHP2	CHP2	CHP2	2533	0.2	0.51	NO
37	SFRP2	SFRP2	SFRP2	2694	0.19	0.51	NO
38	CTNNBIP1	CTNNBIP1	CTNNBIP1	2974	0.17	0.5	NO
39	WNT3	WNT3	WNT3	3088	0.17	0.5	NO
40	NFATC2	NFATC2	NFATC2	3325	0.16	0.49	NO
41	WNT16	WNT16	WNT16	3521	0.15	0.49	NO
42	TCF7L1	TCF7L1	TCF7L1	3522	0.15	0.5	NO
43	PRKCG	PRKCG	PRKCG	3766	0.14	0.49	NO
44	MAPK8	MAPK8	MAPK8	3822	0.13	0.49	NO
45	FZD4	FZD4	FZD4	4392	0.12	0.46	NO
46	TCF7L2	TCF7L2	TCF7L2	4509	0.11	0.46	NO
47	NFATC4	NFATC4	NFATC4	4555	0.11	0.47	NO
48	FZD7	FZD7	FZD7	4559	0.11	0.47	NO
49	PRKX	PRKX	PRKX	4776	0.1	0.46	NO
50	AXIN2	AXIN2	AXIN2	4796	0.1	0.47	NO
51	SENP2	SENP2	SENP2	4970	0.098	0.46	NO
52	NFAT5	NFAT5	NFAT5	4988	0.097	0.47	NO
53	CSNK2A1	CSNK2A1	CSNK2A1	4995	0.097	0.47	NO
54	NFATC3	NFATC3	NFATC3	5116	0.093	0.47	NO
55	APC	APC	APC	5142	0.093	0.47	NO
56	PPP3CA	PPP3CA	PPP3CA	5240	0.09	0.47	NO
57	MMP7	MMP7	MMP7	5369	0.087	0.47	NO
58	WNT10A	WNT10A	WNT10A	5438	0.085	0.47	NO
59	PPP2R1B	PPP2R1B	PPP2R1B	5472	0.084	0.47	NO
60	MAP3K7	MAP3K7	MAP3K7	5517	0.083	0.47	NO
61	CTBP2	CTBP2	CTBP2	5712	0.079	0.46	NO
62	PPP3CB	PPP3CB	PPP3CB	5714	0.079	0.46	NO
63	PPARD	PPARD	PPARD	5744	0.078	0.47	NO
64	MAPK10	MAPK10	MAPK10	5772	0.078	0.47	NO
65	CSNK1E	CSNK1E	CSNK1E	5814	0.077	0.47	NO
66	CHD8	CHD8	CHD8	5890	0.075	0.47	NO
67	NFATC1	NFATC1	NFATC1	5908	0.075	0.47	NO
68	WNT9A	WNT9A	WNT9A	6082	0.071	0.47	NO
69	PRKCA	PRKCA	PRKCA	6097	0.071	0.47	NO
70	DVL2	DVL2	DVL2	6239	0.068	0.46	NO
71	CSNK2A2	CSNK2A2	CSNK2A2	6285	0.068	0.46	NO
72	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.45	NO
73	TBL1XR1	TBL1XR1	TBL1XR1	6689	0.06	0.45	NO
74	EP300	EP300	EP300	6879	0.056	0.44	NO
75	WNT10B	WNT10B	WNT10B	6945	0.055	0.44	NO
76	PLCB4	PLCB4	PLCB4	7056	0.053	0.44	NO
77	JUN	JUN	JUN	7420	0.046	0.42	NO
78	DVL1	DVL1	DVL1	7494	0.045	0.42	NO
79	CTBP1	CTBP1	CTBP1	7723	0.041	0.4	NO
80	CCND3	CCND3	CCND3	7789	0.04	0.4	NO
81	PPP2R1A	PPP2R1A	PPP2R1A	7808	0.04	0.4	NO
82	FBXW11	FBXW11	FBXW11	7903	0.039	0.4	NO
83	CREBBP	CREBBP	CREBBP	8040	0.036	0.39	NO
84	PPP3R1	PPP3R1	PPP3R1	8109	0.035	0.39	NO
85	CSNK1A1L	CSNK1A1L	CSNK1A1L	8311	0.032	0.38	NO
86	PRICKLE2	PRICKLE2	PRICKLE2	8497	0.029	0.37	NO
87	FRAT2	FRAT2	FRAT2	8517	0.029	0.37	NO
88	DVL3	DVL3	DVL3	8623	0.027	0.37	NO
89	PSEN1	PSEN1	PSEN1	8667	0.027	0.37	NO
90	SMAD2	SMAD2	SMAD2	8669	0.027	0.37	NO
91	MYC	MYC	MYC	8716	0.026	0.37	NO
92	PPP2R5D	PPP2R5D	PPP2R5D	8721	0.026	0.37	NO
93	FZD5	FZD5	FZD5	8973	0.022	0.36	NO
94	WNT8B	WNT8B	WNT8B	9106	0.02	0.35	NO
95	SIAH1	SIAH1	SIAH1	9112	0.02	0.35	NO
96	TCF7	TCF7	TCF7	9174	0.019	0.35	NO
97	ROCK2	ROCK2	ROCK2	9344	0.016	0.34	NO
98	PRKACG	PRKACG	PRKACG	9467	0.014	0.33	NO
99	CSNK2B	CSNK2B	CSNK2B	9738	0.01	0.32	NO
100	WNT1	WNT1	WNT1	9871	0.0084	0.31	NO
101	SMAD4	SMAD4	SMAD4	10283	0.0018	0.29	NO
102	NLK	NLK	NLK	10341	0.00097	0.28	NO
103	PPP2CB	PPP2CB	PPP2CB	10417	-0.000072	0.28	NO
104	SKP1	SKP1	SKP1	10437	-0.00041	0.28	NO
105	CHP	CHP	CHP	10632	-0.0036	0.27	NO
106	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.27	NO
107	PPP2R5C	PPP2R5C	PPP2R5C	10804	-0.006	0.26	NO
108	RAC1	RAC1	RAC1	11257	-0.013	0.24	NO
109	FRAT1	FRAT1	FRAT1	11400	-0.015	0.23	NO
110	PPP3R2	PPP3R2	PPP3R2	11477	-0.016	0.22	NO
111	AXIN1	AXIN1	AXIN1	11506	-0.017	0.22	NO
112	CAMK2D	CAMK2D	CAMK2D	11635	-0.019	0.22	NO
113	CUL1	CUL1	CUL1	11681	-0.02	0.22	NO
114	PPP2CA	PPP2CA	PPP2CA	11774	-0.021	0.21	NO
115	SMAD3	SMAD3	SMAD3	11956	-0.024	0.2	NO
116	CSNK1A1	CSNK1A1	CSNK1A1	12073	-0.027	0.2	NO
117	PRKACA	PRKACA	PRKACA	12112	-0.027	0.2	NO
118	WNT2B	WNT2B	WNT2B	12142	-0.028	0.2	NO
119	TBL1X	TBL1X	TBL1X	12200	-0.029	0.2	NO
120	RUVBL1	RUVBL1	RUVBL1	12611	-0.036	0.17	NO
121	RBX1	RBX1	RBX1	12694	-0.038	0.17	NO
122	CACYBP	CACYBP	CACYBP	12903	-0.043	0.16	NO
123	PPP2R5E	PPP2R5E	PPP2R5E	13067	-0.046	0.15	NO
124	MAPK9	MAPK9	MAPK9	13254	-0.05	0.15	NO
125	PPP2R5B	PPP2R5B	PPP2R5B	13339	-0.052	0.14	NO
126	VANGL1	VANGL1	VANGL1	13471	-0.055	0.14	NO
127	PLCB3	PLCB3	PLCB3	13702	-0.06	0.13	NO
128	RHOA	RHOA	RHOA	13795	-0.063	0.13	NO
129	DAAM1	DAAM1	DAAM1	14211	-0.074	0.11	NO
130	PLCB1	PLCB1	PLCB1	14218	-0.074	0.11	NO
131	PRKACB	PRKACB	PRKACB	14396	-0.08	0.1	NO
132	PPP3CC	PPP3CC	PPP3CC	14449	-0.082	0.1	NO
133	DKK1	DKK1	DKK1	14533	-0.085	0.1	NO
134	PORCN	PORCN	PORCN	14636	-0.088	0.1	NO
135	SOX17	SOX17	SOX17	14769	-0.094	0.099	NO
136	WNT2	WNT2	WNT2	14930	-0.099	0.095	NO
137	ROCK1	ROCK1	ROCK1	15020	-0.1	0.095	NO
138	CAMK2G	CAMK2G	CAMK2G	15116	-0.11	0.094	NO
139	PLCB2	PLCB2	PLCB2	15187	-0.11	0.095	NO
140	SFRP4	SFRP4	SFRP4	15255	-0.11	0.097	NO
141	PPP2R5A	PPP2R5A	PPP2R5A	15484	-0.12	0.09	NO
142	FOSL1	FOSL1	FOSL1	15750	-0.14	0.081	NO
143	CAMK2A	CAMK2A	CAMK2A	16154	-0.16	0.066	NO
144	FZD6	FZD6	FZD6	16736	-0.21	0.044	NO
145	WNT9B	WNT9B	WNT9B	16945	-0.23	0.043	NO
146	RAC2	RAC2	RAC2	17197	-0.27	0.041	NO
147	PRKCB	PRKCB	PRKCB	17350	-0.29	0.045	NO

Figure S49. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA WNT PATHWAY.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA WNT PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: WNT SIGNALING

Table S26. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	COL9A3	COL9A3	COL9A3	3	0.91	0.12	YES
2	COL2A1	COL2A1	COL2A1	26	0.73	0.21	YES
3	CACNA1G	CACNA1G	CACNA1G	149	0.57	0.28	YES
4	CNTN2	CNTN2	CNTN2	357	0.48	0.33	YES
5	COL9A1	COL9A1	COL9A1	475	0.45	0.38	YES
6	COL9A2	COL9A2	COL9A2	540	0.43	0.43	YES
7	ST8SIA2	ST8SIA2	ST8SIA2	657	0.4	0.48	YES
8	CACNA1I	CACNA1I	CACNA1I	950	0.35	0.51	YES
9	GFRA1	GFRA1	GFRA1	988	0.34	0.55	YES
10	GFRA2	GFRA2	GFRA2	1188	0.32	0.58	YES
11	COL4A5	COL4A5	COL4A5	1333	0.3	0.61	YES
12	NCAN	NCAN	NCAN	1338	0.3	0.65	YES
13	NCAM1	NCAM1	NCAM1	1389	0.29	0.69	YES
14	COL5A1	COL5A1	COL5A1	2572	0.19	0.65	NO
15	AGRN	AGRN	AGRN	2662	0.19	0.67	NO
16	CACNB3	CACNB3	CACNB3	3036	0.17	0.67	NO
17	GDNF	GDNF	GDNF	3556	0.14	0.66	NO
18	COL1A1	COL1A1	COL1A1	4211	0.12	0.64	NO
19	PSPN	PSPN	PSPN	4782	0.1	0.62	NO
20	NRTN	NRTN	NRTN	4829	0.1	0.63	NO
21	CACNA1H	CACNA1H	CACNA1H	5037	0.096	0.63	NO
22	COL5A2	COL5A2	COL5A2	5202	0.091	0.63	NO
23	CACNA1S	CACNA1S	CACNA1S	5214	0.091	0.64	NO
24	COL1A2	COL1A2	COL1A2	7001	0.054	0.55	NO
25	CACNB2	CACNB2	CACNB2	8016	0.037	0.5	NO
26	CACNB1	CACNB1	CACNB1	8450	0.03	0.48	NO
27	COL4A4	COL4A4	COL4A4	10079	0.0051	0.39	NO
28	COL3A1	COL3A1	COL3A1	10196	0.0033	0.39	NO
29	COL4A3	COL4A3	COL4A3	10483	-0.001	0.37	NO
30	CACNB4	CACNB4	CACNB4	10565	-0.0022	0.37	NO
31	PRNP	PRNP	PRNP	11193	-0.012	0.33	NO
32	COL6A3	COL6A3	COL6A3	11196	-0.012	0.34	NO
33	COL4A1	COL4A1	COL4A1	12567	-0.036	0.26	NO
34	COL4A2	COL4A2	COL4A2	12681	-0.038	0.26	NO
35	COL6A1	COL6A1	COL6A1	12716	-0.038	0.27	NO
36	COL6A2	COL6A2	COL6A2	13029	-0.045	0.26	NO
37	ST8SIA4	ST8SIA4	ST8SIA4	14238	-0.075	0.2	NO
38	ARTN	ARTN	ARTN	15865	-0.14	0.13	NO

Figure S51. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: WNT SIGNALING.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: WNT SIGNALING, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: ST WNT BETA CATENIN PATHWAY

Table S27. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	COL9A3	COL9A3	COL9A3	3	0.91	0.093	YES
2	COL2A1	COL2A1	COL2A1	26	0.73	0.17	YES
3	CACNA1G	CACNA1G	CACNA1G	149	0.57	0.22	YES
4	CNTN2	CNTN2	CNTN2	357	0.48	0.25	YES
5	SPTBN2	SPTBN2	SPTBN2	359	0.48	0.3	YES
6	COL9A1	COL9A1	COL9A1	475	0.45	0.34	YES
7	COL9A2	COL9A2	COL9A2	540	0.43	0.38	YES
8	ST8SIA2	ST8SIA2	ST8SIA2	657	0.4	0.42	YES
9	CACNA1I	CACNA1I	CACNA1I	950	0.35	0.44	YES
10	GFRA1	GFRA1	GFRA1	988	0.34	0.47	YES
11	GFRA2	GFRA2	GFRA2	1188	0.32	0.49	YES
12	COL4A5	COL4A5	COL4A5	1333	0.3	0.51	YES
13	NCAN	NCAN	NCAN	1338	0.3	0.54	YES
14	NCAM1	NCAM1	NCAM1	1389	0.29	0.57	YES
15	COL5A1	COL5A1	COL5A1	2572	0.19	0.52	NO
16	SPTBN4	SPTBN4	SPTBN4	2635	0.19	0.54	NO
17	AGRN	AGRN	AGRN	2662	0.19	0.56	NO
18	CACNB3	CACNB3	CACNB3	3036	0.17	0.55	NO
19	SPTBN5	SPTBN5	SPTBN5	3396	0.15	0.55	NO
20	GDNF	GDNF	GDNF	3556	0.14	0.56	NO
21	COL1A1	COL1A1	COL1A1	4211	0.12	0.53	NO
22	PSPN	PSPN	PSPN	4782	0.1	0.51	NO
23	NRTN	NRTN	NRTN	4829	0.1	0.52	NO
24	NRAS	NRAS	NRAS	4870	0.1	0.53	NO
25	CACNA1H	CACNA1H	CACNA1H	5037	0.096	0.53	NO
26	COL5A2	COL5A2	COL5A2	5202	0.091	0.53	NO
27	CACNA1S	CACNA1S	CACNA1S	5214	0.091	0.54	NO
28	KRAS	KRAS	KRAS	5433	0.085	0.53	NO
29	FGFR1	FGFR1	FGFR1	5777	0.078	0.52	NO
30	SPTBN1	SPTBN1	SPTBN1	6731	0.059	0.48	NO
31	COL1A2	COL1A2	COL1A2	7001	0.054	0.46	NO
32	SOS1	SOS1	SOS1	7453	0.046	0.44	NO
33	PTK2	PTK2	PTK2	7517	0.045	0.45	NO
34	CREB1	CREB1	CREB1	7961	0.038	0.43	NO
35	CACNB2	CACNB2	CACNB2	8016	0.037	0.43	NO
36	CACNB1	CACNB1	CACNB1	8450	0.03	0.4	NO
37	CDK1	CDK1	CDK1	9191	0.018	0.37	NO
38	COL4A4	COL4A4	COL4A4	10079	0.0051	0.32	NO
39	COL3A1	COL3A1	COL3A1	10196	0.0033	0.31	NO
40	COL4A3	COL4A3	COL4A3	10483	-0.001	0.3	NO
41	MAP2K2	MAP2K2	MAP2K2	10505	-0.0014	0.3	NO
42	CACNB4	CACNB4	CACNB4	10565	-0.0022	0.29	NO
43	PRNP	PRNP	PRNP	11193	-0.012	0.26	NO
44	COL6A3	COL6A3	COL6A3	11196	-0.012	0.26	NO
45	RAF1	RAF1	RAF1	11521	-0.017	0.24	NO
46	MAPK1	MAPK1	MAPK1	12006	-0.026	0.22	NO
47	SPTB	SPTB	SPTB	12229	-0.029	0.21	NO
48	HRAS	HRAS	HRAS	12385	-0.033	0.2	NO
49	COL4A1	COL4A1	COL4A1	12567	-0.036	0.2	NO
50	MAPK3	MAPK3	MAPK3	12593	-0.036	0.2	NO
51	COL4A2	COL4A2	COL4A2	12681	-0.038	0.2	NO
52	COL6A1	COL6A1	COL6A1	12716	-0.038	0.2	NO
53	MAP2K1	MAP2K1	MAP2K1	13011	-0.045	0.19	NO
54	COL6A2	COL6A2	COL6A2	13029	-0.045	0.19	NO
55	YWHAB	YWHAB	YWHAB	13088	-0.046	0.2	NO
56	GRB2	GRB2	GRB2	13151	-0.048	0.2	NO
57	SPTAN1	SPTAN1	SPTAN1	13405	-0.053	0.19	NO
58	FYN	FYN	FYN	13637	-0.059	0.18	NO
59	ST8SIA4	ST8SIA4	ST8SIA4	14238	-0.075	0.16	NO
60	SRC	SRC	SRC	15289	-0.11	0.11	NO
61	ARTN	ARTN	ARTN	15865	-0.14	0.092	NO
62	SPTA1	SPTA1	SPTA1	15912	-0.15	0.1	NO
63	RPS6KA5	RPS6KA5	RPS6KA5	16559	-0.2	0.089	NO

Figure S53. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: ST WNT BETA CATENIN PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: ST WNT BETA CATENIN PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID NOTCH PATHWAY

Table S28. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	APC2	APC2	APC2	116	0.59	0.042	YES
2	FZD10	FZD10	FZD10	117	0.59	0.091	YES
3	HHIP	HHIP	HHIP	179	0.55	0.13	YES
4	WNT5A	WNT5A	WNT5A	183	0.55	0.18	YES
5	FZD9	FZD9	FZD9	240	0.52	0.22	YES
6	SMO	SMO	SMO	243	0.52	0.26	YES
7	PTCH1	PTCH1	PTCH1	246	0.52	0.3	YES
8	BMP4	BMP4	BMP4	504	0.44	0.32	YES
9	FZD2	FZD2	FZD2	554	0.43	0.36	YES
10	FZD3	FZD3	FZD3	606	0.41	0.39	YES
11	LEF1	LEF1	LEF1	622	0.41	0.42	YES
12	WNT11	WNT11	WNT11	739	0.38	0.45	YES
13	GLI1	GLI1	GLI1	752	0.38	0.48	YES
14	FZD8	FZD8	FZD8	862	0.36	0.5	YES
15	GLI2	GLI2	GLI2	1028	0.34	0.52	YES
16	WNT4	WNT4	WNT4	1034	0.34	0.55	YES
17	WNT3A	WNT3A	WNT3A	1136	0.32	0.57	YES
18	WNT6	WNT6	WNT6	1174	0.32	0.59	YES
19	BMP2	BMP2	BMP2	1455	0.29	0.6	YES
20	WNT5B	WNT5B	WNT5B	1467	0.28	0.62	YES
21	WNT7A	WNT7A	WNT7A	1585	0.27	0.64	YES
22	WNT7B	WNT7B	WNT7B	1702	0.26	0.65	YES
23	PTCH2	PTCH2	PTCH2	1931	0.24	0.66	YES
24	FZD1	FZD1	FZD1	2084	0.23	0.67	YES
25	TP53	TP53	TP53	2354	0.21	0.67	YES
26	WNT3	WNT3	WNT3	3088	0.17	0.65	NO
27	SUFU	SUFU	SUFU	3317	0.16	0.65	NO
28	WNT16	WNT16	WNT16	3521	0.15	0.65	NO
29	TCF7L1	TCF7L1	TCF7L1	3522	0.15	0.66	NO
30	FZD4	FZD4	FZD4	4392	0.12	0.62	NO
31	TCF7L2	TCF7L2	TCF7L2	4509	0.11	0.62	NO
32	FZD7	FZD7	FZD7	4559	0.11	0.63	NO
33	STK36	STK36	STK36	4739	0.1	0.63	NO
34	AXIN2	AXIN2	AXIN2	4796	0.1	0.64	NO
35	APC	APC	APC	5142	0.093	0.62	NO
36	WNT10A	WNT10A	WNT10A	5438	0.085	0.61	NO
37	GLI3	GLI3	GLI3	5820	0.077	0.6	NO
38	WNT9A	WNT9A	WNT9A	6082	0.071	0.59	NO
39	DVL2	DVL2	DVL2	6239	0.068	0.59	NO
40	CTNNB1	CTNNB1	CTNNB1	6511	0.063	0.58	NO
41	WNT10B	WNT10B	WNT10B	6945	0.055	0.56	NO
42	DVL1	DVL1	DVL1	7494	0.045	0.53	NO
43	DVL3	DVL3	DVL3	8623	0.027	0.47	NO
44	FZD5	FZD5	FZD5	8973	0.022	0.45	NO
45	WNT8B	WNT8B	WNT8B	9106	0.02	0.45	NO
46	TCF7	TCF7	TCF7	9174	0.019	0.45	NO
47	WNT1	WNT1	WNT1	9871	0.0084	0.41	NO
48	GSK3B	GSK3B	GSK3B	10675	-0.0042	0.36	NO
49	AXIN1	AXIN1	AXIN1	11506	-0.017	0.32	NO
50	WNT2B	WNT2B	WNT2B	12142	-0.028	0.29	NO
51	WNT2	WNT2	WNT2	14930	-0.099	0.14	NO
52	FZD6	FZD6	FZD6	16736	-0.21	0.06	NO
53	WNT9B	WNT9B	WNT9B	16945	-0.23	0.068	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID NOTCH PATHWAY.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: PID NOTCH PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID PS1PATHWAY

Table S29. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DLK1	DLK1	DLK1	61	0.66	0.14	YES
2	DTX4	DTX4	DTX4	284	0.5	0.24	YES
3	CNTN1	CNTN1	CNTN1	300	0.5	0.34	YES
4	DTX1	DTX1	DTX1	326	0.49	0.45	YES
5	NEURL	NEURL	NEURL	656	0.4	0.52	YES
6	DLL1	DLL1	DLL1	683	0.4	0.6	YES
7	DNER	DNER	DNER	1870	0.25	0.59	NO
8	MIB1	MIB1	MIB1	3609	0.14	0.53	NO
9	JAG2	JAG2	JAG2	3712	0.14	0.55	NO
10	ADAM17	ADAM17	ADAM17	4481	0.11	0.53	NO
11	APH1A	APH1A	APH1A	5090	0.094	0.52	NO
12	RPS27A	RPS27A	RPS27A	5573	0.082	0.51	NO
13	MIB2	MIB2	MIB2	6850	0.057	0.45	NO
14	PSEN2	PSEN2	PSEN2	7295	0.049	0.44	NO
15	APH1B	APH1B	APH1B	7921	0.038	0.41	NO
16	ADAM10	ADAM10	ADAM10	8144	0.035	0.41	NO
17	PSEN1	PSEN1	PSEN1	8667	0.027	0.39	NO
18	NUMB	NUMB	NUMB	9721	0.011	0.33	NO
19	NCSTN	NCSTN	NCSTN	10412	0.000046	0.29	NO
20	DLL4	DLL4	DLL4	11152	-0.011	0.25	NO
21	UBA52	UBA52	UBA52	11191	-0.012	0.25	NO
22	PSENEN	PSENEN	PSENEN	12203	-0.029	0.2	NO
23	JAG1	JAG1	JAG1	14893	-0.098	0.078	NO
24	ARRB1	ARRB1	ARRB1	15145	-0.11	0.087	NO
25	DTX2	DTX2	DTX2	15572	-0.13	0.092	NO
26	ARRB2	ARRB2	ARRB2	16963	-0.24	0.066	NO

Figure S57. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID PS1PATHWAY.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: PID PS1PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID WNT SIGNALING PATHWAY

Table S30. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DLK1	DLK1	DLK1	61	0.66	0.073	YES
2	DTX4	DTX4	DTX4	284	0.5	0.12	YES
3	CNTN1	CNTN1	CNTN1	300	0.5	0.18	YES
4	DTX1	DTX1	DTX1	326	0.49	0.23	YES
5	NEURL	NEURL	NEURL	656	0.4	0.26	YES
6	DLL1	DLL1	DLL1	683	0.4	0.3	YES
7	HEY1	HEY1	HEY1	802	0.37	0.34	YES
8	TLE1	TLE1	TLE1	1281	0.31	0.35	YES
9	DNER	DNER	DNER	1870	0.25	0.35	YES
10	HES1	HES1	HES1	2140	0.22	0.36	YES
11	HES5	HES5	HES5	2773	0.18	0.34	YES
12	HEYL	HEYL	HEYL	2966	0.17	0.35	YES
13	HDAC4	HDAC4	HDAC4	3040	0.17	0.37	YES
14	TLE4	TLE4	TLE4	3226	0.16	0.38	YES
15	MAML2	MAML2	MAML2	3448	0.15	0.38	YES
16	MIB1	MIB1	MIB1	3609	0.14	0.39	YES
17	TLE3	TLE3	TLE3	3707	0.14	0.4	YES
18	JAG2	JAG2	JAG2	3712	0.14	0.42	YES
19	FBXW7	FBXW7	FBXW7	3886	0.13	0.42	YES
20	CDK8	CDK8	CDK8	4177	0.12	0.42	YES
21	TLE2	TLE2	TLE2	4263	0.12	0.43	YES
22	ADAM17	ADAM17	ADAM17	4481	0.11	0.43	YES
23	MAML1	MAML1	MAML1	4517	0.11	0.44	YES
24	KAT2A	KAT2A	KAT2A	4777	0.1	0.44	NO
25	APH1A	APH1A	APH1A	5090	0.094	0.43	NO
26	CCNC	CCNC	CCNC	5572	0.082	0.42	NO
27	RPS27A	RPS27A	RPS27A	5573	0.082	0.42	NO
28	NCOR2	NCOR2	NCOR2	5595	0.081	0.43	NO
29	HDAC2	HDAC2	HDAC2	6183	0.069	0.41	NO
30	HDAC1	HDAC1	HDAC1	6407	0.065	0.4	NO
31	TBL1XR1	TBL1XR1	TBL1XR1	6689	0.06	0.4	NO
32	HDAC6	HDAC6	HDAC6	6804	0.058	0.4	NO
33	MIB2	MIB2	MIB2	6850	0.057	0.4	NO
34	EP300	EP300	EP300	6879	0.056	0.4	NO
35	PSEN2	PSEN2	PSEN2	7295	0.049	0.39	NO
36	MAML3	MAML3	MAML3	7682	0.042	0.37	NO
37	APH1B	APH1B	APH1B	7921	0.038	0.36	NO
38	CREBBP	CREBBP	CREBBP	8040	0.036	0.36	NO
39	ADAM10	ADAM10	ADAM10	8144	0.035	0.36	NO
40	HDAC8	HDAC8	HDAC8	8583	0.028	0.34	NO
41	PSEN1	PSEN1	PSEN1	8667	0.027	0.34	NO
42	MYC	MYC	MYC	8716	0.026	0.34	NO
43	HDAC3	HDAC3	HDAC3	8958	0.022	0.33	NO
44	NUMB	NUMB	NUMB	9721	0.011	0.28	NO
45	NCSTN	NCSTN	NCSTN	10412	0.000046	0.25	NO
46	SKP1	SKP1	SKP1	10437	-0.00041	0.24	NO
47	DLL4	DLL4	DLL4	11152	-0.011	0.21	NO
48	UBA52	UBA52	UBA52	11191	-0.012	0.21	NO
49	HDAC7	HDAC7	HDAC7	11624	-0.019	0.18	NO
50	CUL1	CUL1	CUL1	11681	-0.02	0.18	NO
51	SNW1	SNW1	SNW1	12178	-0.028	0.16	NO
52	HDAC10	HDAC10	HDAC10	12181	-0.028	0.16	NO
53	TBL1X	TBL1X	TBL1X	12200	-0.029	0.16	NO
54	PSENEN	PSENEN	PSENEN	12203	-0.029	0.17	NO
55	RBX1	RBX1	RBX1	12694	-0.038	0.15	NO
56	NCOR1	NCOR1	NCOR1	12788	-0.04	0.15	NO
57	HIF1A	HIF1A	HIF1A	13000	-0.044	0.14	NO
58	HDAC5	HDAC5	HDAC5	13171	-0.048	0.14	NO
59	MAMLD1	MAMLD1	MAMLD1	13550	-0.057	0.12	NO
60	RBPJ	RBPJ	RBPJ	13553	-0.057	0.13	NO
61	HDAC11	HDAC11	HDAC11	13970	-0.067	0.11	NO
62	HEY2	HEY2	HEY2	14843	-0.096	0.075	NO
63	JAG1	JAG1	JAG1	14893	-0.098	0.084	NO
64	ARRB1	ARRB1	ARRB1	15145	-0.11	0.083	NO
65	DTX2	DTX2	DTX2	15572	-0.13	0.074	NO
66	HDAC9	HDAC9	HDAC9	15808	-0.14	0.078	NO
67	KAT2B	KAT2B	KAT2B	16810	-0.22	0.048	NO
68	ARRB2	ARRB2	ARRB2	16963	-0.24	0.067	NO

Figure S59. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID WNT SIGNALING PATHWAY.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: PID WNT SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

For the top enriched genes, if you want to check whether they are

up-regulated, please check the list of up-regulated genes
down-regulated, please check the list of down-regulated genes

Expression level

For the top enriched genes, if you want to check whether they are

highly expressed genes, please check the list of high (top 30%) expressed genes
low expressed genes, please check the list of low (bottom 30%) expressed genes

An expression pattern of top(30%)/middle(30%)/low(30%) in this subtype against other subtypes is available in a heatmap

Significant gene list

For the top enriched genes, if you want to check whether they are

significantly differently expressed genes by eBayes lm fit, please check the list of significant genes

Methods & Data

Input

Gene set database = c2.cp.v4.0.symbols.gmt
Expression data file = SARC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = SARC-TP.mergedcluster.txt

GSEA analysis

For the Gene Set Enrichment Analysis (GSEA), Broad GSEA-P-R.1.0 version is used with class2: canonical pathways geneses from MSigDB. Further details about statistics are available inThe Broad GSEA website.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

[1] Subramanian, A. et al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles., Proc. Natl. Acad. Sci. USA 102(43) (2005)

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