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

Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in DLBC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C10P0Z10

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 in DLBC-TP. 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: 188
Number of samples: 28
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 2 :[ clus1 ] 15
pheno.type: 2 - 2 :[ clus2 ] 13

For the expression subtypes of 17576 genes in 29 samples, GSEA found enriched gene sets in each cluster using 28 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA INFLAM PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA IL1R PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG PYRIMIDINE METABOLISM, KEGG LYSINE DEGRADATION, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG PYRUVATE METABOLISM

And common core enriched genes are GMPPB, HK2, HK3, DLST, AMDHD2, CHIA, CHIT1, GALE, GALK1, GFPT2

clus2

Top enriched gene sets are BIOCARTA ALK PATHWAY, BIOCARTA CARM ER PATHWAY, BIOCARTA GH PATHWAY, BIOCARTA TCR PATHWAY, KEGG FATTY ACID METABOLISM, KEGG ABC TRANSPORTERS, KEGG CARDIAC MUSCLE CONTRACTION, KEGG WNT SIGNALING PATHWAY, KEGG CELL ADHESION MOLECULES CAMS, KEGG INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION

And common core enriched genes are CDH1, LEF1, TCF7, TCF7L1, GH1, HNF1A, IRS1, PLCG1, PRKCA, PRKCB

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
BIOCARTA INFLAM PATHWAY	25	genes.ES.table	0.58	1.3	0.1	0.56	0.97	0.4	0.19	0.32	0.51	0.12
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.42	1.5	0.071	0.41	0.84	0.52	0.36	0.34	0.31	0.083
BIOCARTA IL1R PATHWAY	31	genes.ES.table	0.55	1.5	0.067	0.39	0.89	0.36	0.19	0.29	0.31	0.053
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.49	1.7	0.034	0.41	0.42	0.59	0.34	0.39	0	0.14
KEGG PENTOSE PHOSPHATE PATHWAY	26	genes.ES.table	0.52	1.4	0.15	0.54	0.96	0.58	0.25	0.43	0.48	0.11
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.52	1.7	0.012	0.31	0.46	0.34	0.2	0.28	0	0.082
KEGG PYRIMIDINE METABOLISM	97	genes.ES.table	0.35	1.5	0.054	0.43	0.83	0.3	0.22	0.23	0.32	0.098
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.43	1.7	0.026	0.32	0.56	0.37	0.24	0.28	0.17	0.078
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.51	1.9	0.0098	0.12	0.086	0.51	0.26	0.38	0	0.046
KEGG PYRUVATE METABOLISM	37	genes.ES.table	0.41	1.3	0.16	0.59	0.97	0.43	0.24	0.33	0.53	0.14

genes ES table in pathway: BIOCARTA INFLAM PATHWAY

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	HK3	HK3	HK3	184	0.49	0.1	YES
2	GFPT2	GFPT2	GFPT2	206	0.48	0.21	YES
3	CHIT1	CHIT1	CHIT1	491	0.36	0.28	YES
4	NPL	NPL	NPL	1329	0.21	0.28	YES
5	HEXB	HEXB	HEXB	1685	0.18	0.3	YES
6	HK2	HK2	HK2	1761	0.17	0.33	YES
7	PGM3	PGM3	PGM3	1806	0.17	0.37	YES
8	GMPPB	GMPPB	GMPPB	2421	0.13	0.37	YES
9	PGM2	PGM2	PGM2	2525	0.12	0.39	YES
10	PGM1	PGM1	PGM1	2853	0.11	0.39	YES
11	GALE	GALE	GALE	3056	0.1	0.41	YES
12	CHIA	CHIA	CHIA	3152	0.096	0.42	YES
13	GALK1	GALK1	GALK1	3266	0.091	0.44	YES
14	HEXA	HEXA	HEXA	3274	0.091	0.46	YES
15	RENBP	RENBP	RENBP	3292	0.09	0.48	YES
16	GNE	GNE	GNE	3547	0.08	0.48	YES
17	UGP2	UGP2	UGP2	3705	0.076	0.49	YES
18	UAP1	UAP1	UAP1	3822	0.072	0.5	YES
19	HK1	HK1	HK1	4210	0.061	0.49	YES
20	AMDHD2	AMDHD2	AMDHD2	4284	0.058	0.5	YES
21	GNPNAT1	GNPNAT1	GNPNAT1	4525	0.052	0.5	YES
22	PMM2	PMM2	PMM2	4571	0.051	0.51	YES
23	GPI	GPI	GPI	5231	0.037	0.48	NO
24	GMPPA	GMPPA	GMPPA	5563	0.031	0.47	NO
25	UGDH	UGDH	UGDH	5679	0.029	0.47	NO
26	CMAS	CMAS	CMAS	5939	0.024	0.46	NO
27	PMM1	PMM1	PMM1	6015	0.023	0.46	NO
28	CYB5R1	CYB5R1	CYB5R1	6193	0.02	0.45	NO
29	MPI	MPI	MPI	6279	0.019	0.45	NO
30	GMDS	GMDS	GMDS	6590	0.014	0.44	NO
31	GALK2	GALK2	GALK2	6744	0.012	0.43	NO
32	NANS	NANS	NANS	6903	0.0097	0.42	NO
33	NANP	NANP	NANP	6958	0.0089	0.42	NO
34	FPGT	FPGT	FPGT	8567	-0.013	0.34	NO
35	GFPT1	GFPT1	GFPT1	9707	-0.029	0.28	NO
36	TSTA3	TSTA3	TSTA3	10251	-0.038	0.25	NO
37	NAGK	NAGK	NAGK	10351	-0.039	0.26	NO
38	UXS1	UXS1	UXS1	10551	-0.043	0.26	NO
39	GNPDA2	GNPDA2	GNPDA2	11170	-0.054	0.23	NO
40	GALT	GALT	GALT	11503	-0.061	0.23	NO
41	GNPDA1	GNPDA1	GNPDA1	12057	-0.074	0.21	NO
42	FUK	FUK	FUK	12350	-0.08	0.22	NO
43	GCK	GCK	GCK	16631	-0.36	0.053	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: BIOCARTA INFLAM PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA INFLAM 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 RACCYCD PATHWAY

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	PC	PC	PC	781	0.29	0.12	YES
2	ACO1	ACO1	ACO1	908	0.27	0.26	YES
3	IDH1	IDH1	IDH1	1681	0.18	0.32	YES
4	PCK2	PCK2	PCK2	2970	0.1	0.3	YES
5	DLAT	DLAT	DLAT	3464	0.083	0.32	YES
6	IDH3A	IDH3A	IDH3A	3625	0.078	0.36	YES
7	DLST	DLST	DLST	3955	0.068	0.38	YES
8	PCK1	PCK1	PCK1	4162	0.062	0.4	YES
9	ACLY	ACLY	ACLY	4448	0.054	0.41	YES
10	SDHB	SDHB	SDHB	4818	0.045	0.42	YES
11	SDHA	SDHA	SDHA	4826	0.045	0.44	YES
12	IDH2	IDH2	IDH2	4958	0.042	0.46	YES
13	CS	CS	CS	5280	0.036	0.46	YES
14	SUCLA2	SUCLA2	SUCLA2	5408	0.034	0.47	YES
15	DLD	DLD	DLD	5438	0.033	0.49	YES
16	MDH2	MDH2	MDH2	5858	0.025	0.48	YES
17	SDHD	SDHD	SDHD	5899	0.025	0.49	YES
18	SDHC	SDHC	SDHC	6418	0.017	0.47	NO
19	MDH1	MDH1	MDH1	6746	0.012	0.46	NO
20	OGDH	OGDH	OGDH	7606	0.000046	0.41	NO
21	SUCLG1	SUCLG1	SUCLG1	7785	-0.0025	0.4	NO
22	SUCLG2	SUCLG2	SUCLG2	7997	-0.0057	0.39	NO
23	IDH3B	IDH3B	IDH3B	8122	-0.0073	0.39	NO
24	PDHA1	PDHA1	PDHA1	8231	-0.0087	0.39	NO
25	ACO2	ACO2	ACO2	8675	-0.015	0.37	NO
26	PDHB	PDHB	PDHB	8908	-0.018	0.36	NO
27	IDH3G	IDH3G	IDH3G	9764	-0.03	0.33	NO
28	FH	FH	FH	11210	-0.055	0.28	NO
29	OGDHL	OGDHL	OGDHL	14234	-0.14	0.19	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: BIOCARTA RACCYCD PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA RACCYCD 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 IL1R PATHWAY

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	HK3	HK3	HK3	184	0.49	0.14	YES
2	PFKFB3	PFKFB3	PFKFB3	341	0.41	0.26	YES
3	PFKFB4	PFKFB4	PFKFB4	363	0.4	0.38	YES
4	FBP1	FBP1	FBP1	1135	0.24	0.4	YES
5	HK2	HK2	HK2	1761	0.17	0.42	YES
6	PFKP	PFKP	PFKP	2333	0.14	0.43	YES
7	GMPPB	GMPPB	GMPPB	2421	0.13	0.46	YES
8	SORD	SORD	SORD	2675	0.12	0.48	YES
9	AKR1B1	AKR1B1	AKR1B1	3035	0.1	0.5	YES
10	ALDOB	ALDOB	ALDOB	3165	0.095	0.52	YES
11	TPI1	TPI1	TPI1	3484	0.082	0.52	YES
12	HK1	HK1	HK1	4210	0.061	0.5	NO
13	PMM2	PMM2	PMM2	4571	0.051	0.5	NO
14	MTMR2	MTMR2	MTMR2	5153	0.038	0.47	NO
15	MTMR6	MTMR6	MTMR6	5508	0.032	0.46	NO
16	GMPPA	GMPPA	GMPPA	5563	0.031	0.47	NO
17	PMM1	PMM1	PMM1	6015	0.023	0.45	NO
18	MPI	MPI	MPI	6279	0.019	0.44	NO
19	GMDS	GMDS	GMDS	6590	0.014	0.43	NO
20	PFKL	PFKL	PFKL	7251	0.0048	0.39	NO
21	PHPT1	PHPT1	PHPT1	7672	-0.00097	0.37	NO
22	ALDOC	ALDOC	ALDOC	7829	-0.0029	0.36	NO
23	PFKM	PFKM	PFKM	7872	-0.0035	0.36	NO
24	FPGT	FPGT	FPGT	8567	-0.013	0.32	NO
25	KHK	KHK	KHK	9270	-0.023	0.29	NO
26	TSTA3	TSTA3	TSTA3	10251	-0.038	0.24	NO
27	PFKFB2	PFKFB2	PFKFB2	10279	-0.038	0.26	NO
28	MTMR1	MTMR1	MTMR1	11123	-0.053	0.22	NO
29	MTMR7	MTMR7	MTMR7	11216	-0.055	0.24	NO
30	FUK	FUK	FUK	12350	-0.08	0.2	NO
31	PFKFB1	PFKFB1	PFKFB1	14620	-0.17	0.12	NO
32	FBP2	FBP2	FBP2	14687	-0.17	0.16	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: BIOCARTA IL1R PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R 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 CITRATE CYCLE TCA CYCLE

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	PLOD2	PLOD2	PLOD2	62	0.64	0.2	YES
2	BBOX1	BBOX1	BBOX1	1809	0.17	0.15	YES
3	PLOD1	PLOD1	PLOD1	1875	0.17	0.2	YES
4	ACAT2	ACAT2	ACAT2	2358	0.13	0.21	YES
5	PIPOX	PIPOX	PIPOX	2453	0.13	0.25	YES
6	TMLHE	TMLHE	TMLHE	2495	0.12	0.29	YES
7	ACAT1	ACAT1	ACAT1	3195	0.094	0.28	YES
8	SUV39H2	SUV39H2	SUV39H2	3254	0.092	0.3	YES
9	PLOD3	PLOD3	PLOD3	3332	0.089	0.32	YES
10	ALDH2	ALDH2	ALDH2	3701	0.076	0.33	YES
11	SETD7	SETD7	SETD7	3770	0.074	0.35	YES
12	DLST	DLST	DLST	3955	0.068	0.36	YES
13	WHSC1L1	WHSC1L1	WHSC1L1	4025	0.066	0.38	YES
14	SUV39H1	SUV39H1	SUV39H1	4029	0.066	0.4	YES
15	SETD8	SETD8	SETD8	4128	0.063	0.41	YES
16	ALDH1B1	ALDH1B1	ALDH1B1	4193	0.061	0.42	YES
17	WHSC1	WHSC1	WHSC1	6056	0.022	0.33	NO
18	HADHA	HADHA	HADHA	6221	0.02	0.32	NO
19	AASDH	AASDH	AASDH	6911	0.0096	0.29	NO
20	HADH	HADH	HADH	7113	0.0065	0.28	NO
21	SETMAR	SETMAR	SETMAR	7197	0.0056	0.27	NO
22	SETDB2	SETDB2	SETDB2	7432	0.0023	0.26	NO
23	SUV420H1	SUV420H1	SUV420H1	7438	0.0022	0.26	NO
24	OGDH	OGDH	OGDH	7606	0.000046	0.25	NO
25	GCDH	GCDH	GCDH	8309	-0.0097	0.22	NO
26	AASDHPPT	AASDHPPT	AASDHPPT	8533	-0.013	0.21	NO
27	NSD1	NSD1	NSD1	8629	-0.014	0.21	NO
28	SETD2	SETD2	SETD2	8730	-0.016	0.2	NO
29	DOT1L	DOT1L	DOT1L	8795	-0.016	0.21	NO
30	AADAT	AADAT	AADAT	9739	-0.03	0.16	NO
31	SETD1A	SETD1A	SETD1A	10030	-0.034	0.16	NO
32	ECHS1	ECHS1	ECHS1	10113	-0.036	0.16	NO
33	ALDH9A1	ALDH9A1	ALDH9A1	10370	-0.04	0.16	NO
34	ALDH3A2	ALDH3A2	ALDH3A2	10635	-0.044	0.16	NO
35	SETDB1	SETDB1	SETDB1	10956	-0.05	0.16	NO
36	ALDH7A1	ALDH7A1	ALDH7A1	11372	-0.058	0.15	NO
37	AASS	AASS	AASS	12202	-0.077	0.13	NO
38	SUV420H2	SUV420H2	SUV420H2	12235	-0.078	0.15	NO
39	EHMT1	EHMT1	EHMT1	12265	-0.079	0.17	NO
40	SETD1B	SETD1B	SETD1B	12284	-0.079	0.2	NO
41	EHMT2	EHMT2	EHMT2	12352	-0.08	0.22	NO
42	ASH1L	ASH1L	ASH1L	13147	-0.1	0.21	NO
43	OGDHL	OGDHL	OGDHL	14234	-0.14	0.19	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 CITRATE CYCLE TCA CYCLE.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CITRATE CYCLE TCA CYCLE, 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 PENTOSE PHOSPHATE 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	DNA2	DNA2	DNA2	1691	0.18	-0.0058	YES
2	POLE2	POLE2	POLE2	2093	0.15	0.047	YES
3	PRIM1	PRIM1	PRIM1	2329	0.14	0.1	YES
4	POLD3	POLD3	POLD3	2594	0.12	0.15	YES
5	MCM4	MCM4	MCM4	2739	0.11	0.2	YES
6	POLA2	POLA2	POLA2	2949	0.1	0.24	YES
7	RPA3	RPA3	RPA3	3143	0.096	0.28	YES
8	POLD1	POLD1	POLD1	3530	0.081	0.3	YES
9	MCM6	MCM6	MCM6	3739	0.074	0.32	YES
10	FEN1	FEN1	FEN1	3859	0.071	0.35	YES
11	PRIM2	PRIM2	PRIM2	3912	0.069	0.38	YES
12	MCM3	MCM3	MCM3	3921	0.069	0.42	YES
13	RNASEH1	RNASEH1	RNASEH1	3925	0.069	0.45	YES
14	RFC4	RFC4	RFC4	3927	0.069	0.49	YES
15	PCNA	PCNA	PCNA	4004	0.067	0.52	YES
16	RFC3	RFC3	RFC3	4251	0.059	0.53	YES
17	RFC5	RFC5	RFC5	4434	0.054	0.55	YES
18	MCM7	MCM7	MCM7	4568	0.051	0.57	YES
19	RNASEH2A	RNASEH2A	RNASEH2A	4685	0.048	0.58	YES
20	MCM2	MCM2	MCM2	4806	0.046	0.6	YES
21	POLE	POLE	POLE	5570	0.031	0.57	NO
22	POLD4	POLD4	POLD4	5594	0.03	0.59	NO
23	LIG1	LIG1	LIG1	5868	0.025	0.58	NO
24	RFC2	RFC2	RFC2	6034	0.023	0.58	NO
25	RFC1	RFC1	RFC1	7152	0.006	0.52	NO
26	POLD2	POLD2	POLD2	7301	0.004	0.52	NO
27	RNASEH2C	RNASEH2C	RNASEH2C	7421	0.0024	0.51	NO
28	MCM5	MCM5	MCM5	7501	0.0014	0.51	NO
29	POLE3	POLE3	POLE3	7511	0.0012	0.51	NO
30	RPA4	RPA4	RPA4	7892	-0.0038	0.49	NO
31	SSBP1	SSBP1	SSBP1	7980	-0.0054	0.49	NO
32	RPA2	RPA2	RPA2	8696	-0.015	0.45	NO
33	POLE4	POLE4	POLE4	9381	-0.025	0.43	NO
34	RPA1	RPA1	RPA1	9885	-0.032	0.42	NO
35	RNASEH2B	RNASEH2B	RNASEH2B	10736	-0.046	0.39	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 PENTOSE PHOSPHATE PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE PHOSPHATE 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 FRUCTOSE AND MANNOSE METABOLISM

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	SLC11A1	SLC11A1	SLC11A1	8	0.88	0.077	YES
2	CTSK	CTSK	CTSK	430	0.38	0.087	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	666	0.32	0.1	YES
4	CTSL1	CTSL1	CTSL1	921	0.27	0.11	YES
5	GLA	GLA	GLA	1087	0.24	0.12	YES
6	CTSB	CTSB	CTSB	1337	0.21	0.13	YES
7	HEXB	HEXB	HEXB	1685	0.18	0.12	YES
8	GALC	GALC	GALC	1801	0.17	0.13	YES
9	ARSB	ARSB	ARSB	1837	0.17	0.14	YES
10	CTSW	CTSW	CTSW	1913	0.16	0.16	YES
11	SCARB2	SCARB2	SCARB2	1938	0.16	0.17	YES
12	SORT1	SORT1	SORT1	1951	0.16	0.18	YES
13	ACP5	ACP5	ACP5	2050	0.15	0.19	YES
14	ACP2	ACP2	ACP2	2105	0.15	0.2	YES
15	CTSD	CTSD	CTSD	2110	0.15	0.21	YES
16	CD68	CD68	CD68	2196	0.14	0.22	YES
17	GLB1	GLB1	GLB1	2245	0.14	0.23	YES
18	PSAP	PSAP	PSAP	2385	0.13	0.23	YES
19	SLC17A5	SLC17A5	SLC17A5	2398	0.13	0.24	YES
20	NPC1	NPC1	NPC1	2475	0.13	0.25	YES
21	GNS	GNS	GNS	2481	0.13	0.26	YES
22	LAMP2	LAMP2	LAMP2	2581	0.12	0.27	YES
23	ASAH1	ASAH1	ASAH1	2600	0.12	0.28	YES
24	DNASE2B	DNASE2B	DNASE2B	2711	0.12	0.28	YES
25	ATP6V1H	ATP6V1H	ATP6V1H	2759	0.11	0.29	YES
26	GALNS	GALNS	GALNS	2851	0.11	0.29	YES
27	CD63	CD63	CD63	2863	0.11	0.3	YES
28	GM2A	GM2A	GM2A	2912	0.11	0.31	YES
29	LGMN	LGMN	LGMN	3003	0.1	0.31	YES
30	IGF2R	IGF2R	IGF2R	3023	0.1	0.32	YES
31	LAPTM4B	LAPTM4B	LAPTM4B	3108	0.098	0.32	YES
32	NAGA	NAGA	NAGA	3126	0.097	0.33	YES
33	ENTPD4	ENTPD4	ENTPD4	3130	0.097	0.34	YES
34	ATP6V0D1	ATP6V0D1	ATP6V0D1	3175	0.095	0.34	YES
35	GBA	GBA	GBA	3179	0.095	0.35	YES
36	CTSS	CTSS	CTSS	3183	0.094	0.36	YES
37	CTSL2	CTSL2	CTSL2	3198	0.094	0.37	YES
38	HEXA	HEXA	HEXA	3274	0.091	0.37	YES
39	GAA	GAA	GAA	3275	0.091	0.38	YES
40	CTSZ	CTSZ	CTSZ	3352	0.088	0.38	YES
41	DNASE2	DNASE2	DNASE2	3425	0.085	0.39	YES
42	TCIRG1	TCIRG1	TCIRG1	3685	0.076	0.38	YES
43	ATP6AP1	ATP6AP1	ATP6AP1	3707	0.076	0.38	YES
44	ATP6V0B	ATP6V0B	ATP6V0B	3801	0.072	0.39	YES
45	NEU1	NEU1	NEU1	3886	0.07	0.39	YES
46	ARSA	ARSA	ARSA	3975	0.067	0.39	YES
47	CTSA	CTSA	CTSA	4019	0.066	0.39	YES
48	SLC11A2	SLC11A2	SLC11A2	4044	0.065	0.4	YES
49	NAPSA	NAPSA	NAPSA	4095	0.064	0.4	YES
50	ATP6V0C	ATP6V0C	ATP6V0C	4134	0.063	0.4	YES
51	MANBA	MANBA	MANBA	4140	0.063	0.41	YES
52	AGA	AGA	AGA	4472	0.053	0.39	NO
53	CTSH	CTSH	CTSH	4649	0.049	0.39	NO
54	AP4E1	AP4E1	AP4E1	4693	0.048	0.39	NO
55	PPT1	PPT1	PPT1	4764	0.047	0.39	NO
56	AP4M1	AP4M1	AP4M1	4909	0.044	0.38	NO
57	LAPTM4A	LAPTM4A	LAPTM4A	4995	0.042	0.38	NO
58	LIPA	LIPA	LIPA	5002	0.042	0.39	NO
59	LAMP1	LAMP1	LAMP1	5018	0.041	0.39	NO
60	NAGLU	NAGLU	NAGLU	5102	0.039	0.39	NO
61	MAN2B1	MAN2B1	MAN2B1	5197	0.037	0.39	NO
62	AP3M2	AP3M2	AP3M2	5242	0.037	0.39	NO
63	IDS	IDS	IDS	5620	0.03	0.37	NO
64	M6PR	M6PR	M6PR	5940	0.024	0.35	NO
65	AP3S1	AP3S1	AP3S1	5960	0.024	0.35	NO
66	NPC2	NPC2	NPC2	5967	0.024	0.36	NO
67	CLTA	CLTA	CLTA	5973	0.024	0.36	NO
68	GNPTAB	GNPTAB	GNPTAB	5998	0.023	0.36	NO
69	SUMF1	SUMF1	SUMF1	6092	0.022	0.35	NO
70	PLA2G15	PLA2G15	PLA2G15	6421	0.017	0.34	NO
71	CLTC	CLTC	CLTC	6463	0.016	0.34	NO
72	TPP1	TPP1	TPP1	6551	0.015	0.33	NO
73	AP1S2	AP1S2	AP1S2	6598	0.014	0.33	NO
74	AP3B1	AP3B1	AP3B1	7085	0.007	0.3	NO
75	GGA2	GGA2	GGA2	7318	0.0038	0.29	NO
76	CTNS	CTNS	CTNS	7400	0.0027	0.29	NO
77	AP3M1	AP3M1	AP3M1	7424	0.0024	0.28	NO
78	AP3S2	AP3S2	AP3S2	7490	0.0015	0.28	NO
79	CTSC	CTSC	CTSC	7613	-0.000051	0.27	NO
80	CLN3	CLN3	CLN3	7739	-0.002	0.27	NO
81	SMPD1	SMPD1	SMPD1	8272	-0.0092	0.24	NO
82	NAGPA	NAGPA	NAGPA	8380	-0.011	0.23	NO
83	AP3D1	AP3D1	AP3D1	8594	-0.014	0.22	NO
84	AP4B1	AP4B1	AP4B1	8639	-0.014	0.22	NO
85	PPT2	PPT2	PPT2	8797	-0.016	0.21	NO
86	AP1B1	AP1B1	AP1B1	8825	-0.017	0.21	NO
87	GGA3	GGA3	GGA3	8830	-0.017	0.21	NO
88	CTSO	CTSO	CTSO	8923	-0.018	0.21	NO
89	GNPTG	GNPTG	GNPTG	9251	-0.023	0.19	NO
90	MCOLN1	MCOLN1	MCOLN1	9710	-0.03	0.17	NO
91	GUSB	GUSB	GUSB	9728	-0.03	0.17	NO
92	ATP6V0A1	ATP6V0A1	ATP6V0A1	10011	-0.034	0.16	NO
93	CLTB	CLTB	CLTB	10082	-0.035	0.16	NO
94	SGSH	SGSH	SGSH	10169	-0.037	0.16	NO
95	AP1S1	AP1S1	AP1S1	10193	-0.037	0.16	NO
96	AP1G1	AP1G1	AP1G1	10194	-0.037	0.16	NO
97	ATP6V0A2	ATP6V0A2	ATP6V0A2	10384	-0.04	0.15	NO
98	MFSD8	MFSD8	MFSD8	10613	-0.044	0.14	NO
99	AP1M1	AP1M1	AP1M1	10619	-0.044	0.15	NO
100	LAPTM5	LAPTM5	LAPTM5	11085	-0.052	0.13	NO
101	CD164	CD164	CD164	11342	-0.058	0.12	NO
102	ARSG	ARSG	ARSG	11575	-0.062	0.11	NO
103	HYAL1	HYAL1	HYAL1	12194	-0.076	0.08	NO
104	CTSF	CTSF	CTSF	12622	-0.087	0.063	NO
105	CLN5	CLN5	CLN5	12815	-0.092	0.06	NO
106	GGA1	GGA1	GGA1	12975	-0.096	0.06	NO
107	AP1S3	AP1S3	AP1S3	13304	-0.11	0.05	NO
108	FUCA1	FUCA1	FUCA1	13644	-0.12	0.041	NO
109	AP4S1	AP4S1	AP4S1	14269	-0.15	0.019	NO
110	IDUA	IDUA	IDUA	14286	-0.15	0.031	NO
111	AP1M2	AP1M2	AP1M2	14569	-0.16	0.029	NO
112	ABCA2	ABCA2	ABCA2	14729	-0.17	0.035	NO
113	AP3B2	AP3B2	AP3B2	14794	-0.18	0.048	NO
114	CTSE	CTSE	CTSE	14883	-0.18	0.059	NO
115	LAMP3	LAMP3	LAMP3	15501	-0.23	0.043	NO
116	CLTCL1	CLTCL1	CLTCL1	15564	-0.23	0.06	NO
117	CTSG	CTSG	CTSG	16167	-0.29	0.052	NO
118	ABCB9	ABCB9	ABCB9	16390	-0.32	0.067	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 FRUCTOSE AND MANNOSE METABOLISM.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FRUCTOSE AND MANNOSE 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 PYRIMIDINE METABOLISM

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	SPP1	SPP1	SPP1	14	0.81	0.094	YES
2	IL8	IL8	IL8	221	0.47	0.14	YES
3	IL6	IL6	IL6	334	0.42	0.18	YES
4	CTSK	CTSK	CTSK	430	0.38	0.22	YES
5	TLR8	TLR8	TLR8	588	0.33	0.25	YES
6	MAPK8	MAPK8	MAPK8	725	0.3	0.28	YES
7	TLR2	TLR2	TLR2	777	0.29	0.31	YES
8	FOS	FOS	FOS	794	0.29	0.34	YES
9	CD14	CD14	CD14	1114	0.24	0.35	YES
10	MAPK10	MAPK10	MAPK10	1226	0.22	0.37	YES
11	IL1B	IL1B	IL1B	1390	0.21	0.38	YES
12	TLR1	TLR1	TLR1	1602	0.19	0.4	YES
13	CCL3	CCL3	CCL3	1800	0.17	0.4	YES
14	CCL4	CCL4	CCL4	1812	0.17	0.42	YES
15	MAP3K8	MAP3K8	MAP3K8	1954	0.16	0.43	YES
16	CD80	CD80	CD80	2144	0.15	0.44	YES
17	JUN	JUN	JUN	2150	0.15	0.46	YES
18	TLR3	TLR3	TLR3	2599	0.12	0.44	YES
19	TLR4	TLR4	TLR4	2749	0.11	0.45	YES
20	IFNB1	IFNB1	IFNB1	2858	0.11	0.46	YES
21	TICAM2	TICAM2	TICAM2	2922	0.11	0.46	YES
22	CHUK	CHUK	CHUK	3001	0.1	0.47	YES
23	CXCL10	CXCL10	CXCL10	3188	0.094	0.47	YES
24	IFNAR2	IFNAR2	IFNAR2	3616	0.078	0.46	NO
25	PIK3CG	PIK3CG	PIK3CG	3754	0.074	0.46	NO
26	CD40	CD40	CD40	3933	0.068	0.46	NO
27	CCL5	CCL5	CCL5	4045	0.065	0.46	NO
28	AKT3	AKT3	AKT3	4274	0.059	0.45	NO
29	IFNA21	IFNA21	IFNA21	4442	0.054	0.45	NO
30	IFNAR1	IFNAR1	IFNAR1	4524	0.052	0.45	NO
31	STAT1	STAT1	STAT1	4616	0.05	0.45	NO
32	IRAK1	IRAK1	IRAK1	4702	0.048	0.45	NO
33	MAPK11	MAPK11	MAPK11	5154	0.038	0.43	NO
34	MAPK13	MAPK13	MAPK13	5275	0.036	0.43	NO
35	NFKB1	NFKB1	NFKB1	5452	0.033	0.42	NO
36	FADD	FADD	FADD	5541	0.031	0.42	NO
37	AKT1	AKT1	AKT1	5625	0.03	0.42	NO
38	MAPK14	MAPK14	MAPK14	5815	0.026	0.41	NO
39	MYD88	MYD88	MYD88	5922	0.024	0.41	NO
40	PIK3CA	PIK3CA	PIK3CA	5953	0.024	0.41	NO
41	RIPK1	RIPK1	RIPK1	6051	0.022	0.4	NO
42	CXCL11	CXCL11	CXCL11	6172	0.02	0.4	NO
43	MAP3K7	MAP3K7	MAP3K7	6456	0.016	0.39	NO
44	TICAM1	TICAM1	TICAM1	6468	0.016	0.39	NO
45	LY96	LY96	LY96	6513	0.015	0.39	NO
46	TIRAP	TIRAP	TIRAP	6525	0.015	0.39	NO
47	PIK3CB	PIK3CB	PIK3CB	6558	0.015	0.39	NO
48	CD86	CD86	CD86	6616	0.014	0.39	NO
49	RELA	RELA	RELA	6691	0.012	0.38	NO
50	MAPK9	MAPK9	MAPK9	6730	0.012	0.38	NO
51	IKBKG	IKBKG	IKBKG	7106	0.0066	0.36	NO
52	RAC1	RAC1	RAC1	7174	0.0058	0.36	NO
53	PIK3R1	PIK3R1	PIK3R1	7176	0.0058	0.36	NO
54	MAPK3	MAPK3	MAPK3	7202	0.0055	0.36	NO
55	TNF	TNF	TNF	7433	0.0023	0.35	NO
56	MAPK1	MAPK1	MAPK1	7463	0.002	0.34	NO
57	MAP2K1	MAP2K1	MAP2K1	7506	0.0013	0.34	NO
58	MAP2K3	MAP2K3	MAP2K3	7616	-0.00012	0.34	NO
59	AKT2	AKT2	AKT2	7663	-0.0008	0.33	NO
60	MAPK12	MAPK12	MAPK12	7946	-0.0047	0.32	NO
61	MAP2K6	MAP2K6	MAP2K6	7993	-0.0056	0.32	NO
62	NFKBIA	NFKBIA	NFKBIA	8172	-0.0078	0.31	NO
63	TAB2	TAB2	TAB2	8282	-0.0093	0.3	NO
64	MAP2K4	MAP2K4	MAP2K4	8889	-0.018	0.27	NO
65	TOLLIP	TOLLIP	TOLLIP	9017	-0.019	0.26	NO
66	IL12A	IL12A	IL12A	9080	-0.02	0.26	NO
67	IRAK4	IRAK4	IRAK4	9199	-0.022	0.26	NO
68	CXCL9	CXCL9	CXCL9	9450	-0.026	0.25	NO
69	PIK3R2	PIK3R2	PIK3R2	9652	-0.028	0.24	NO
70	IRF5	IRF5	IRF5	10235	-0.038	0.21	NO
71	MAP2K2	MAP2K2	MAP2K2	10917	-0.05	0.18	NO
72	TRAF3	TRAF3	TRAF3	10947	-0.05	0.18	NO
73	PIK3CD	PIK3CD	PIK3CD	10951	-0.05	0.19	NO
74	IRF3	IRF3	IRF3	10953	-0.05	0.19	NO
75	TAB1	TAB1	TAB1	11256	-0.056	0.18	NO
76	TRAF6	TRAF6	TRAF6	11431	-0.059	0.18	NO
77	IKBKE	IKBKE	IKBKE	11572	-0.062	0.18	NO
78	PIK3R5	PIK3R5	PIK3R5	11719	-0.065	0.18	NO
79	MAP2K7	MAP2K7	MAP2K7	11806	-0.067	0.18	NO
80	CASP8	CASP8	CASP8	11809	-0.067	0.19	NO
81	TLR5	TLR5	TLR5	12282	-0.079	0.17	NO
82	IKBKB	IKBKB	IKBKB	12515	-0.085	0.17	NO
83	IRF7	IRF7	IRF7	12535	-0.085	0.18	NO
84	PIK3R3	PIK3R3	PIK3R3	12626	-0.087	0.18	NO
85	TLR6	TLR6	TLR6	13200	-0.1	0.16	NO
86	LBP	LBP	LBP	14526	-0.16	0.1	NO
87	IL12B	IL12B	IL12B	14572	-0.16	0.12	NO
88	TLR7	TLR7	TLR7	15249	-0.21	0.11	NO
89	TLR9	TLR9	TLR9	15499	-0.23	0.12	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 PYRIMIDINE METABOLISM.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PYRIMIDINE 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 LYSINE DEGRADATION

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	SMC1B	SMC1B	SMC1B	1232	0.22	-0.046	YES
2	GADD45G	GADD45G	GADD45G	1249	0.22	-0.022	YES
3	SFN	SFN	SFN	1281	0.22	0.00018	YES
4	TGFB3	TGFB3	TGFB3	1477	0.2	0.011	YES
5	E2F2	E2F2	E2F2	1492	0.2	0.032	YES
6	MAD2L1	MAD2L1	MAD2L1	1660	0.18	0.042	YES
7	ESPL1	ESPL1	ESPL1	1678	0.18	0.062	YES
8	CCNA2	CCNA2	CCNA2	1736	0.18	0.078	YES
9	CDKN1A	CDKN1A	CDKN1A	1748	0.18	0.096	YES
10	CCNE2	CCNE2	CCNE2	1787	0.17	0.11	YES
11	BUB1B	BUB1B	BUB1B	1907	0.16	0.12	YES
12	CDK2	CDK2	CDK2	1960	0.16	0.14	YES
13	PLK1	PLK1	PLK1	2022	0.16	0.15	YES
14	PKMYT1	PKMYT1	PKMYT1	2124	0.15	0.16	YES
15	CDC45	CDC45	CDC45	2198	0.14	0.18	YES
16	CHEK1	CHEK1	CHEK1	2200	0.14	0.19	YES
17	CDK1	CDK1	CDK1	2207	0.14	0.21	YES
18	ORC1L	ORC1L	ORC1L	2208	0.14	0.22	YES
19	E2F1	E2F1	E2F1	2213	0.14	0.24	YES
20	RBL1	RBL1	RBL1	2218	0.14	0.25	YES
21	CDC25C	CDC25C	CDC25C	2244	0.14	0.27	YES
22	CCNB2	CCNB2	CCNB2	2443	0.13	0.27	YES
23	CDC14B	CDC14B	CDC14B	2728	0.12	0.26	YES
24	MCM4	MCM4	MCM4	2739	0.11	0.28	YES
25	CCNE1	CCNE1	CCNE1	2764	0.11	0.29	YES
26	PTTG2	PTTG2	PTTG2	2886	0.11	0.29	YES
27	SKP2	SKP2	SKP2	2977	0.1	0.3	YES
28	CCNB1	CCNB1	CCNB1	2983	0.1	0.31	YES
29	CDC6	CDC6	CDC6	3018	0.1	0.32	YES
30	BUB1	BUB1	BUB1	3021	0.1	0.33	YES
31	CDKN2D	CDKN2D	CDKN2D	3093	0.098	0.34	YES
32	CDK6	CDK6	CDK6	3150	0.096	0.34	YES
33	STAG1	STAG1	STAG1	3212	0.093	0.35	YES
34	CDC25A	CDC25A	CDC25A	3277	0.091	0.36	YES
35	TGFB2	TGFB2	TGFB2	3294	0.09	0.37	YES
36	YWHAH	YWHAH	YWHAH	3691	0.076	0.35	YES
37	MCM6	MCM6	MCM6	3739	0.074	0.36	YES
38	TTK	TTK	TTK	3794	0.073	0.36	YES
39	MCM3	MCM3	MCM3	3921	0.069	0.36	YES
40	PTTG1	PTTG1	PTTG1	3973	0.068	0.37	YES
41	CDC20	CDC20	CDC20	3999	0.067	0.38	YES
42	PCNA	PCNA	PCNA	4004	0.067	0.38	YES
43	ANAPC10	ANAPC10	ANAPC10	4038	0.066	0.39	YES
44	CCNA1	CCNA1	CCNA1	4046	0.065	0.39	YES
45	GADD45A	GADD45A	GADD45A	4054	0.065	0.4	YES
46	CCND1	CCND1	CCND1	4113	0.064	0.4	YES
47	CDC14A	CDC14A	CDC14A	4184	0.062	0.41	YES
48	CDK4	CDK4	CDK4	4324	0.057	0.41	YES
49	YWHAQ	YWHAQ	YWHAQ	4423	0.054	0.41	YES
50	TFDP2	TFDP2	TFDP2	4455	0.054	0.41	YES
51	MCM7	MCM7	MCM7	4568	0.051	0.41	YES
52	SMC3	SMC3	SMC3	4738	0.047	0.4	YES
53	YWHAG	YWHAG	YWHAG	4796	0.046	0.41	YES
54	MCM2	MCM2	MCM2	4806	0.046	0.41	YES
55	GSK3B	GSK3B	GSK3B	4858	0.045	0.41	YES
56	RAD21	RAD21	RAD21	5033	0.041	0.41	YES
57	ORC6L	ORC6L	ORC6L	5065	0.04	0.41	YES
58	HDAC1	HDAC1	HDAC1	5151	0.038	0.41	YES
59	PRKDC	PRKDC	PRKDC	5203	0.037	0.41	YES
60	MAD2L2	MAD2L2	MAD2L2	5204	0.037	0.42	YES
61	SMC1A	SMC1A	SMC1A	5262	0.036	0.42	YES
62	CDKN2C	CDKN2C	CDKN2C	5306	0.035	0.42	YES
63	CDC26	CDC26	CDC26	5449	0.033	0.41	NO
64	ABL1	ABL1	ABL1	5506	0.032	0.41	NO
65	CDC25B	CDC25B	CDC25B	5584	0.03	0.41	NO
66	CDC27	CDC27	CDC27	5769	0.027	0.4	NO
67	CDK7	CDK7	CDK7	6038	0.022	0.39	NO
68	SKP1	SKP1	SKP1	6045	0.022	0.39	NO
69	ANAPC1	ANAPC1	ANAPC1	6098	0.022	0.39	NO
70	ORC4L	ORC4L	ORC4L	6121	0.021	0.39	NO
71	ORC2L	ORC2L	ORC2L	6203	0.02	0.39	NO
72	CUL1	CUL1	CUL1	6267	0.019	0.39	NO
73	ANAPC5	ANAPC5	ANAPC5	6311	0.018	0.39	NO
74	CDC23	CDC23	CDC23	6523	0.015	0.38	NO
75	HDAC2	HDAC2	HDAC2	6686	0.013	0.37	NO
76	YWHAB	YWHAB	YWHAB	6915	0.0095	0.36	NO
77	ATR	ATR	ATR	7209	0.0054	0.34	NO
78	YWHAE	YWHAE	YWHAE	7212	0.0053	0.34	NO
79	BUB3	BUB3	BUB3	7451	0.0021	0.33	NO
80	TGFB1	TGFB1	TGFB1	7493	0.0015	0.33	NO
81	MCM5	MCM5	MCM5	7501	0.0014	0.33	NO
82	E2F4	E2F4	E2F4	7530	0.00093	0.33	NO
83	SMAD2	SMAD2	SMAD2	7556	0.00065	0.32	NO
84	E2F3	E2F3	E2F3	7849	-0.0032	0.31	NO
85	WEE2	WEE2	WEE2	7874	-0.0036	0.31	NO
86	WEE1	WEE1	WEE1	7999	-0.0057	0.3	NO
87	RBX1	RBX1	RBX1	8066	-0.0064	0.3	NO
88	ANAPC7	ANAPC7	ANAPC7	8071	-0.0065	0.3	NO
89	ORC5L	ORC5L	ORC5L	8174	-0.0079	0.29	NO
90	YWHAZ	YWHAZ	YWHAZ	8292	-0.0094	0.29	NO
91	ANAPC2	ANAPC2	ANAPC2	8635	-0.014	0.27	NO
92	FZR1	FZR1	FZR1	8710	-0.015	0.27	NO
93	GADD45B	GADD45B	GADD45B	8712	-0.015	0.27	NO
94	RB1	RB1	RB1	8866	-0.017	0.26	NO
95	CDKN2A	CDKN2A	CDKN2A	8899	-0.018	0.26	NO
96	ANAPC13	ANAPC13	ANAPC13	9022	-0.02	0.26	NO
97	EP300	EP300	EP300	9095	-0.021	0.26	NO
98	STAG2	STAG2	STAG2	9253	-0.023	0.25	NO
99	CCNH	CCNH	CCNH	9380	-0.025	0.24	NO
100	ANAPC4	ANAPC4	ANAPC4	9566	-0.027	0.24	NO
101	CCND3	CCND3	CCND3	9658	-0.028	0.24	NO
102	TFDP1	TFDP1	TFDP1	9772	-0.03	0.23	NO
103	MYC	MYC	MYC	9799	-0.031	0.23	NO
104	ANAPC11	ANAPC11	ANAPC11	10115	-0.036	0.22	NO
105	TP53	TP53	TP53	10271	-0.038	0.22	NO
106	CDKN2B	CDKN2B	CDKN2B	10315	-0.039	0.22	NO
107	MDM2	MDM2	MDM2	10472	-0.041	0.21	NO
108	CHEK2	CHEK2	CHEK2	10695	-0.045	0.2	NO
109	ZBTB17	ZBTB17	ZBTB17	10709	-0.046	0.21	NO
110	SMAD4	SMAD4	SMAD4	10784	-0.047	0.21	NO
111	MAD1L1	MAD1L1	MAD1L1	10889	-0.049	0.21	NO
112	CDC7	CDC7	CDC7	11060	-0.052	0.2	NO
113	CDKN1B	CDKN1B	CDKN1B	12090	-0.074	0.16	NO
114	CCNB3	CCNB3	CCNB3	12384	-0.081	0.15	NO
115	RBL2	RBL2	RBL2	12520	-0.085	0.15	NO
116	E2F5	E2F5	E2F5	12526	-0.085	0.16	NO
117	ATM	ATM	ATM	12612	-0.087	0.16	NO
118	CREBBP	CREBBP	CREBBP	12832	-0.092	0.16	NO
119	ORC3L	ORC3L	ORC3L	13028	-0.098	0.16	NO
120	CDC16	CDC16	CDC16	13341	-0.11	0.15	NO
121	SMAD3	SMAD3	SMAD3	14908	-0.18	0.084	NO
122	CDKN1C	CDKN1C	CDKN1C	16234	-0.3	0.041	NO
123	CCND2	CCND2	CCND2	16362	-0.32	0.069	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 LYSINE DEGRADATION.

Figure S16. 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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

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	ENTPD3	ENTPD3	ENTPD3	90	0.58	0.067	YES
2	CDA	CDA	CDA	210	0.48	0.12	YES
3	CMPK2	CMPK2	CMPK2	911	0.27	0.11	YES
4	NT5E	NT5E	NT5E	1086	0.24	0.13	YES
5	DPYD	DPYD	DPYD	1242	0.22	0.15	YES
6	TYMP	TYMP	TYMP	1530	0.19	0.16	YES
7	NT5C1A	NT5C1A	NT5C1A	1535	0.19	0.18	YES
8	UCK2	UCK2	UCK2	1778	0.17	0.19	YES
9	NME5	NME5	NME5	1859	0.17	0.2	YES
10	UPP1	UPP1	UPP1	2066	0.15	0.21	YES
11	POLE2	POLE2	POLE2	2093	0.15	0.23	YES
12	TYMS	TYMS	TYMS	2311	0.14	0.23	YES
13	PRIM1	PRIM1	PRIM1	2329	0.14	0.25	YES
14	NME6	NME6	NME6	2534	0.12	0.25	YES
15	POLA1	POLA1	POLA1	2568	0.12	0.26	YES
16	POLD3	POLD3	POLD3	2594	0.12	0.28	YES
17	TXNRD1	TXNRD1	TXNRD1	2666	0.12	0.29	YES
18	PNP	PNP	PNP	2705	0.12	0.3	YES
19	POLR3D	POLR3D	POLR3D	2861	0.11	0.3	YES
20	RRM2	RRM2	RRM2	2893	0.11	0.32	YES
21	POLA2	POLA2	POLA2	2949	0.1	0.32	YES
22	ENTPD4	ENTPD4	ENTPD4	3130	0.097	0.33	YES
23	DPYS	DPYS	DPYS	3235	0.092	0.33	YES
24	NT5C1B	NT5C1B	NT5C1B	3433	0.084	0.33	YES
25	RRM1	RRM1	RRM1	3478	0.083	0.34	YES
26	POLD1	POLD1	POLD1	3530	0.081	0.34	YES
27	NME7	NME7	NME7	3750	0.074	0.34	YES
28	TK1	TK1	TK1	3776	0.073	0.35	YES
29	PRIM2	PRIM2	PRIM2	3912	0.069	0.35	YES
30	NME1-NME2	NME1-NME2	NME1-NME2	4221	0.06	0.34	NO
31	POLR3A	POLR3A	POLR3A	4272	0.059	0.34	NO
32	PNPT1	PNPT1	PNPT1	4385	0.055	0.34	NO
33	DTYMK	DTYMK	DTYMK	4660	0.049	0.33	NO
34	DCK	DCK	DCK	4692	0.048	0.34	NO
35	POLR2B	POLR2B	POLR2B	4741	0.047	0.34	NO
36	POLR3K	POLR3K	POLR3K	4903	0.044	0.34	NO
37	TK2	TK2	TK2	4984	0.042	0.34	NO
38	CTPS2	CTPS2	CTPS2	5075	0.04	0.34	NO
39	RRM2B	RRM2B	RRM2B	5410	0.034	0.32	NO
40	DUT	DUT	DUT	5486	0.032	0.32	NO
41	POLE	POLE	POLE	5570	0.031	0.32	NO
42	POLR1A	POLR1A	POLR1A	5592	0.03	0.32	NO
43	POLD4	POLD4	POLD4	5594	0.03	0.33	NO
44	CANT1	CANT1	CANT1	5644	0.029	0.33	NO
45	POLR2G	POLR2G	POLR2G	5832	0.026	0.32	NO
46	POLR3F	POLR3F	POLR3F	5861	0.025	0.32	NO
47	UPRT	UPRT	UPRT	5880	0.025	0.32	NO
48	ENTPD5	ENTPD5	ENTPD5	6039	0.022	0.32	NO
49	NME1	NME1	NME1	6048	0.022	0.32	NO
50	POLR2D	POLR2D	POLR2D	6271	0.019	0.31	NO
51	POLR2L	POLR2L	POLR2L	6695	0.012	0.29	NO
52	ENTPD1	ENTPD1	ENTPD1	6696	0.012	0.29	NO
53	POLR3H	POLR3H	POLR3H	7184	0.0058	0.26	NO
54	POLR2K	POLR2K	POLR2K	7213	0.0053	0.26	NO
55	POLR3B	POLR3B	POLR3B	7220	0.0052	0.26	NO
56	POLD2	POLD2	POLD2	7301	0.004	0.26	NO
57	POLR2H	POLR2H	POLR2H	7373	0.0031	0.25	NO
58	POLE3	POLE3	POLE3	7511	0.0012	0.25	NO
59	UCKL1	UCKL1	UCKL1	7546	0.00078	0.24	NO
60	ITPA	ITPA	ITPA	7581	0.00034	0.24	NO
61	UMPS	UMPS	UMPS	7686	-0.0012	0.24	NO
62	CAD	CAD	CAD	8300	-0.0096	0.2	NO
63	POLR1E	POLR1E	POLR1E	8317	-0.0098	0.2	NO
64	DHODH	DHODH	DHODH	8429	-0.011	0.2	NO
65	ENTPD6	ENTPD6	ENTPD6	8518	-0.012	0.19	NO
66	POLR3C	POLR3C	POLR3C	8539	-0.013	0.19	NO
67	POLR1C	POLR1C	POLR1C	8560	-0.013	0.2	NO
68	CMPK1	CMPK1	CMPK1	8652	-0.014	0.19	NO
69	NUDT2	NUDT2	NUDT2	8805	-0.016	0.18	NO
70	AK3	AK3	AK3	8868	-0.017	0.18	NO
71	POLR2F	POLR2F	POLR2F	9144	-0.022	0.17	NO
72	NME2	NME2	NME2	9254	-0.023	0.17	NO
73	TXNRD2	TXNRD2	TXNRD2	9273	-0.023	0.17	NO
74	POLE4	POLE4	POLE4	9381	-0.025	0.16	NO
75	POLR2E	POLR2E	POLR2E	9499	-0.026	0.16	NO
76	DCTD	DCTD	DCTD	9542	-0.027	0.16	NO
77	POLR2C	POLR2C	POLR2C	9565	-0.027	0.16	NO
78	UPB1	UPB1	UPB1	9918	-0.033	0.15	NO
79	NT5C2	NT5C2	NT5C2	9957	-0.033	0.15	NO
80	POLR3G	POLR3G	POLR3G	10002	-0.034	0.15	NO
81	ZNRD1	ZNRD1	ZNRD1	10043	-0.034	0.15	NO
82	POLR2J	POLR2J	POLR2J	10153	-0.036	0.15	NO
83	UCK1	UCK1	UCK1	10166	-0.036	0.16	NO
84	POLR2A	POLR2A	POLR2A	10375	-0.04	0.15	NO
85	POLR2I	POLR2I	POLR2I	10892	-0.049	0.13	NO
86	NT5C3	NT5C3	NT5C3	10908	-0.049	0.13	NO
87	NT5C	NT5C	NT5C	11196	-0.054	0.12	NO
88	POLR1D	POLR1D	POLR1D	11265	-0.056	0.12	NO
89	POLR1B	POLR1B	POLR1B	12103	-0.075	0.085	NO
90	POLR3GL	POLR3GL	POLR3GL	12119	-0.075	0.094	NO
91	NME3	NME3	NME3	14028	-0.14	0.00086	NO
92	ENTPD8	ENTPD8	ENTPD8	14405	-0.15	-0.0018	NO
93	NME4	NME4	NME4	14614	-0.17	0.0066	NO
94	POLR2J3	POLR2J3	POLR2J3	15314	-0.21	-0.0074	NO
95	UPP2	UPP2	UPP2	16120	-0.29	-0.018	NO
96	POLR2J2	POLR2J2	POLR2J2	16794	-0.39	-0.0095	NO
97	NT5M	NT5M	NT5M	17006	-0.44	0.032	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S18. 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 PYRUVATE METABOLISM

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	CDKN1A	CDKN1A	CDKN1A	1748	0.18	0.049	YES
2	CDK2	CDK2	CDK2	1960	0.16	0.17	YES
3	CCNE1	CCNE1	CCNE1	2764	0.11	0.22	YES
4	CHUK	CHUK	CHUK	3001	0.1	0.3	YES
5	CDK6	CDK6	CDK6	3150	0.096	0.37	YES
6	CCND1	CCND1	CCND1	4113	0.064	0.37	YES
7	CDK4	CDK4	CDK4	4324	0.057	0.4	YES
8	NFKB1	NFKB1	NFKB1	5452	0.033	0.37	YES
9	AKT1	AKT1	AKT1	5625	0.03	0.38	YES
10	PAK1	PAK1	PAK1	5777	0.027	0.4	YES
11	PIK3CA	PIK3CA	PIK3CA	5953	0.024	0.41	YES
12	RAF1	RAF1	RAF1	6027	0.023	0.42	YES
13	RHOA	RHOA	RHOA	6276	0.019	0.42	YES
14	RELA	RELA	RELA	6691	0.012	0.41	NO
15	IKBKG	IKBKG	IKBKG	7106	0.0066	0.39	NO
16	RAC1	RAC1	RAC1	7174	0.0058	0.4	NO
17	PIK3R1	PIK3R1	PIK3R1	7176	0.0058	0.4	NO
18	MAPK3	MAPK3	MAPK3	7202	0.0055	0.4	NO
19	MAPK1	MAPK1	MAPK1	7463	0.002	0.39	NO
20	HRAS	HRAS	HRAS	7916	-0.0042	0.37	NO
21	NFKBIA	NFKBIA	NFKBIA	8172	-0.0078	0.36	NO
22	RB1	RB1	RB1	8866	-0.017	0.34	NO
23	TFDP1	TFDP1	TFDP1	9772	-0.03	0.31	NO
24	CDKN1B	CDKN1B	CDKN1B	12090	-0.074	0.24	NO
25	IKBKB	IKBKB	IKBKB	12515	-0.085	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 PYRUVATE METABOLISM.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PYRUVATE METABOLISM, 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
BIOCARTA ALK PATHWAY	34	genes.ES.table	0.46	1.3	0.1	1	0.98	0.26	0.13	0.23	0.97	0.49
BIOCARTA CARM ER PATHWAY	33	genes.ES.table	0.35	1.3	0.18	1	0.99	0.27	0.28	0.2	0.97	0.48
BIOCARTA GH PATHWAY	26	genes.ES.table	0.55	1.7	0.006	0.98	0.43	0.38	0.29	0.27	0	0.3
BIOCARTA TCR PATHWAY	43	genes.ES.table	0.37	1.2	0.22	0.95	1	0.35	0.26	0.26	0.88	0.41
KEGG FATTY ACID METABOLISM	35	genes.ES.table	0.37	1.3	0.21	0.95	0.99	0.086	0.086	0.078	0.88	0.41
KEGG ABC TRANSPORTERS	41	genes.ES.table	0.56	1.5	0.011	1	0.78	0.46	0.24	0.35	1	0.55
KEGG CARDIAC MUSCLE CONTRACTION	63	genes.ES.table	0.43	1.4	0.051	1	0.96	0.22	0.13	0.19	0.99	0.49
KEGG WNT SIGNALING PATHWAY	140	genes.ES.table	0.39	1.3	0.098	1	0.98	0.21	0.15	0.18	1	0.51
KEGG CELL ADHESION MOLECULES CAMS	126	genes.ES.table	0.43	1.3	0.17	0.99	0.99	0.33	0.18	0.28	0.91	0.42
KEGG INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION	44	genes.ES.table	0.45	1.3	0.16	1	0.99	0.3	0.15	0.25	1	0.5

genes ES table in pathway: BIOCARTA ALK PATHWAY

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	HNF1A	HNF1A	HNF1A	1660	0.26	0.036	YES
2	PRKCA	PRKCA	PRKCA	1756	0.25	0.16	YES
3	PRKCB	PRKCB	PRKCB	1791	0.25	0.28	YES
4	GH1	GH1	GH1	1977	0.23	0.38	YES
5	IRS1	IRS1	IRS1	2476	0.2	0.45	YES
6	PLCG1	PLCG1	PLCG1	4157	0.11	0.41	YES
7	SLC2A4	SLC2A4	SLC2A4	4292	0.1	0.45	YES
8	PTPN6	PTPN6	PTPN6	4321	0.1	0.5	YES
9	SOCS1	SOCS1	SOCS1	4399	0.1	0.55	YES
10	SOS1	SOS1	SOS1	5097	0.083	0.55	YES
11	SRF	SRF	SRF	7990	0.028	0.4	NO
12	STAT5B	STAT5B	STAT5B	8460	0.021	0.38	NO
13	GHR	GHR	GHR	9021	0.013	0.36	NO
14	STAT5A	STAT5A	STAT5A	9532	0.0061	0.33	NO
15	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.3	NO
16	MAPK1	MAPK1	MAPK1	10098	-0.002	0.3	NO
17	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.29	NO
18	PIK3R1	PIK3R1	PIK3R1	10385	-0.0058	0.29	NO
19	JAK2	JAK2	JAK2	10896	-0.013	0.27	NO
20	SHC1	SHC1	SHC1	11438	-0.021	0.25	NO
21	RPS6KA1	RPS6KA1	RPS6KA1	11466	-0.022	0.26	NO
22	RAF1	RAF1	RAF1	11534	-0.023	0.26	NO
23	PIK3CA	PIK3CA	PIK3CA	11608	-0.024	0.27	NO
24	GRB2	GRB2	GRB2	11623	-0.024	0.28	NO
25	INSR	INSR	INSR	12451	-0.039	0.26	NO
26	PIK3CG	PIK3CG	PIK3CG	13807	-0.074	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: BIOCARTA ALK PATHWAY.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ALK 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 CARM ER PATHWAY

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	ABCA3	ABCA3	ABCA3	185	0.61	0.1	YES
2	ABCC6	ABCC6	ABCC6	666	0.41	0.15	YES
3	ABCG2	ABCG2	ABCG2	997	0.35	0.2	YES
4	ABCB9	ABCB9	ABCB9	1171	0.32	0.25	YES
5	ABCA10	ABCA10	ABCA10	1181	0.32	0.31	YES
6	ABCA9	ABCA9	ABCA9	1436	0.29	0.35	YES
7	ABCB11	ABCB11	ABCB11	2185	0.22	0.35	YES
8	ABCA6	ABCA6	ABCA6	2242	0.21	0.38	YES
9	ABCA2	ABCA2	ABCA2	2832	0.17	0.38	YES
10	ABCC11	ABCC11	ABCC11	2960	0.17	0.4	YES
11	ABCA4	ABCA4	ABCA4	2987	0.16	0.44	YES
12	ABCG5	ABCG5	ABCG5	3274	0.15	0.45	YES
13	ABCG1	ABCG1	ABCG1	3284	0.15	0.47	YES
14	ABCB4	ABCB4	ABCB4	3304	0.15	0.5	YES
15	ABCB1	ABCB1	ABCB1	3341	0.14	0.52	YES
16	ABCC5	ABCC5	ABCC5	3500	0.14	0.54	YES
17	ABCA7	ABCA7	ABCA7	3589	0.13	0.56	YES
18	ABCC8	ABCC8	ABCC8	4048	0.11	0.56	YES
19	ABCA5	ABCA5	ABCA5	4270	0.1	0.56	YES
20	ABCC2	ABCC2	ABCC2	5162	0.081	0.53	NO
21	ABCC3	ABCC3	ABCC3	5416	0.075	0.53	NO
22	ABCB5	ABCB5	ABCB5	6165	0.059	0.5	NO
23	ABCD1	ABCD1	ABCD1	6377	0.054	0.49	NO
24	ABCC9	ABCC9	ABCC9	6683	0.049	0.49	NO
25	ABCD4	ABCD4	ABCD4	7686	0.032	0.43	NO
26	ABCC1	ABCC1	ABCC1	7956	0.028	0.42	NO
27	ABCB10	ABCB10	ABCB10	8809	0.016	0.38	NO
28	ABCA12	ABCA12	ABCA12	9508	0.0063	0.34	NO
29	ABCC10	ABCC10	ABCC10	10972	-0.014	0.26	NO
30	ABCA1	ABCA1	ABCA1	11525	-0.022	0.23	NO
31	ABCB8	ABCB8	ABCB8	11694	-0.025	0.23	NO
32	ABCG4	ABCG4	ABCG4	11699	-0.025	0.23	NO
33	ABCB7	ABCB7	ABCB7	12074	-0.032	0.22	NO
34	TAP2	TAP2	TAP2	12142	-0.033	0.22	NO
35	ABCB6	ABCB6	ABCB6	12535	-0.041	0.2	NO
36	TAP1	TAP1	TAP1	13007	-0.051	0.19	NO
37	CFTR	CFTR	CFTR	13290	-0.059	0.18	NO
38	ABCD2	ABCD2	ABCD2	13348	-0.061	0.19	NO
39	ABCD3	ABCD3	ABCD3	13777	-0.073	0.18	NO
40	ABCA13	ABCA13	ABCA13	13992	-0.08	0.18	NO
41	ABCC4	ABCC4	ABCC4	14882	-0.12	0.15	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: BIOCARTA CARM ER PATHWAY.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CARM ER 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 GH PATHWAY

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	CD40LG	CD40LG	CD40LG	66	0.78	0.18	YES
2	AIRE	AIRE	AIRE	107	0.7	0.34	YES
3	IGLL1	IGLL1	IGLL1	1497	0.28	0.33	YES
4	ICOS	ICOS	ICOS	1509	0.28	0.39	YES
5	ZAP70	ZAP70	ZAP70	2098	0.22	0.41	YES
6	CD3E	CD3E	CD3E	2749	0.18	0.42	YES
7	CD3D	CD3D	CD3D	3001	0.16	0.44	YES
8	LCK	LCK	LCK	3078	0.16	0.48	YES
9	RAG1	RAG1	RAG1	3347	0.14	0.49	YES
10	CD79A	CD79A	CD79A	3494	0.14	0.52	YES
11	RFXAP	RFXAP	RFXAP	3665	0.13	0.54	YES
12	TNFRSF13C	TNFRSF13C	TNFRSF13C	5240	0.08	0.47	NO
13	CD19	CD19	CD19	5268	0.079	0.48	NO
14	BTK	BTK	BTK	6244	0.057	0.44	NO
15	IL2RG	IL2RG	IL2RG	6470	0.052	0.44	NO
16	DCLRE1C	DCLRE1C	DCLRE1C	6703	0.048	0.44	NO
17	RFX5	RFX5	RFX5	7285	0.038	0.42	NO
18	AICDA	AICDA	AICDA	7498	0.035	0.41	NO
19	BLNK	BLNK	BLNK	8078	0.026	0.38	NO
20	JAK3	JAK3	JAK3	8211	0.024	0.38	NO
21	RFXANK	RFXANK	RFXANK	8284	0.023	0.38	NO
22	PTPRC	PTPRC	PTPRC	9229	0.01	0.33	NO
23	IKBKG	IKBKG	IKBKG	10455	-0.0066	0.26	NO
24	CD4	CD4	CD4	10829	-0.012	0.25	NO
25	UNG	UNG	UNG	11236	-0.018	0.23	NO
26	TNFRSF13B	TNFRSF13B	TNFRSF13B	11652	-0.024	0.21	NO
27	TAP2	TAP2	TAP2	12142	-0.033	0.19	NO
28	CIITA	CIITA	CIITA	12279	-0.036	0.19	NO
29	TAP1	TAP1	TAP1	13007	-0.051	0.16	NO
30	CD40	CD40	CD40	13628	-0.068	0.14	NO
31	CD8B	CD8B	CD8B	14054	-0.082	0.14	NO
32	ADA	ADA	ADA	14772	-0.11	0.12	NO
33	IL7R	IL7R	IL7R	15616	-0.16	0.11	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: BIOCARTA GH PATHWAY.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA GH 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 TCR PATHWAY

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	CDH1	CDH1	CDH1	183	0.61	0.16	YES
2	TCF7	TCF7	TCF7	389	0.49	0.3	YES
3	RXRG	RXRG	RXRG	740	0.39	0.39	YES
4	RET	RET	RET	782	0.38	0.5	YES
5	TCF7L1	TCF7L1	TCF7L1	1795	0.25	0.51	YES
6	LEF1	LEF1	LEF1	2274	0.21	0.55	YES
7	TCF7L2	TCF7L2	TCF7L2	5527	0.073	0.38	NO
8	NTRK1	NTRK1	NTRK1	5630	0.07	0.4	NO
9	RXRB	RXRB	RXRB	5702	0.069	0.41	NO
10	MAP2K2	MAP2K2	MAP2K2	6644	0.05	0.37	NO
11	TP53	TP53	TP53	7290	0.038	0.34	NO
12	CCDC6	CCDC6	CCDC6	7388	0.037	0.35	NO
13	MYC	MYC	MYC	7762	0.031	0.34	NO
14	RXRA	RXRA	RXRA	9146	0.011	0.26	NO
15	TPR	TPR	TPR	9547	0.0059	0.24	NO
16	TFG	TFG	TFG	9728	0.003	0.23	NO
17	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.21	NO
18	MAPK1	MAPK1	MAPK1	10098	-0.002	0.21	NO
19	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.2	NO
20	TPM3	TPM3	TPM3	10925	-0.014	0.17	NO
21	KRAS	KRAS	KRAS	11611	-0.024	0.14	NO
22	CTNNB1	CTNNB1	CTNNB1	12534	-0.041	0.097	NO
23	NCOA4	NCOA4	NCOA4	12594	-0.042	0.11	NO
24	CCND1	CCND1	CCND1	13448	-0.064	0.076	NO
25	NRAS	NRAS	NRAS	13630	-0.068	0.085	NO
26	BRAF	BRAF	BRAF	14910	-0.12	0.046	NO
27	PAX8	PAX8	PAX8	14987	-0.12	0.077	NO
28	PPARG	PPARG	PPARG	16456	-0.24	0.063	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: BIOCARTA TCR PATHWAY.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TCR 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 FATTY ACID METABOLISM

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	CDH1	CDH1	CDH1	183	0.61	0.12	YES
2	TCF7	TCF7	TCF7	389	0.49	0.22	YES
3	CTNNA3	CTNNA3	CTNNA3	1569	0.27	0.21	YES
4	EGFR	EGFR	EGFR	1574	0.27	0.27	YES
5	AXIN2	AXIN2	AXIN2	1775	0.25	0.32	YES
6	TCF7L1	TCF7L1	TCF7L1	1795	0.25	0.37	YES
7	LEF1	LEF1	LEF1	2274	0.21	0.39	YES
8	ERBB2	ERBB2	ERBB2	3111	0.16	0.38	YES
9	FOXO3	FOXO3	FOXO3	3358	0.14	0.4	YES
10	EGF	EGF	EGF	3676	0.13	0.41	YES
11	CTNNA2	CTNNA2	CTNNA2	3815	0.12	0.43	YES
12	APC2	APC2	APC2	3829	0.12	0.45	YES
13	PIK3R3	PIK3R3	PIK3R3	4935	0.087	0.41	NO
14	SOS1	SOS1	SOS1	5097	0.083	0.42	NO
15	TCF7L2	TCF7L2	TCF7L2	5527	0.073	0.41	NO
16	PIK3R5	PIK3R5	PIK3R5	5842	0.065	0.4	NO
17	PIK3CD	PIK3CD	PIK3CD	6610	0.05	0.37	NO
18	MAP2K2	MAP2K2	MAP2K2	6644	0.05	0.38	NO
19	TP53	TP53	TP53	7290	0.038	0.35	NO
20	MYC	MYC	MYC	7762	0.031	0.33	NO
21	PIK3R2	PIK3R2	PIK3R2	7909	0.028	0.33	NO
22	SOS2	SOS2	SOS2	8082	0.026	0.33	NO
23	AXIN1	AXIN1	AXIN1	8529	0.02	0.31	NO
24	BAD	BAD	BAD	9492	0.0065	0.25	NO
25	AKT2	AKT2	AKT2	9898	0.0008	0.23	NO
26	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.22	NO
27	PDPK1	PDPK1	PDPK1	10075	-0.0015	0.22	NO
28	MAPK1	MAPK1	MAPK1	10098	-0.002	0.22	NO
29	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.2	NO
30	PIK3R1	PIK3R1	PIK3R1	10385	-0.0058	0.2	NO
31	CASP9	CASP9	CASP9	10548	-0.008	0.2	NO
32	PIK3CB	PIK3CB	PIK3CB	11003	-0.015	0.18	NO
33	PTEN	PTEN	PTEN	11207	-0.018	0.17	NO
34	RAF1	RAF1	RAF1	11534	-0.023	0.15	NO
35	PIK3CA	PIK3CA	PIK3CA	11608	-0.024	0.16	NO
36	KRAS	KRAS	KRAS	11611	-0.024	0.16	NO
37	GRB2	GRB2	GRB2	11623	-0.024	0.16	NO
38	APC	APC	APC	11761	-0.026	0.16	NO
39	ARAF	ARAF	ARAF	11932	-0.03	0.16	NO
40	AKT1	AKT1	AKT1	11936	-0.03	0.17	NO
41	CTNNB1	CTNNB1	CTNNB1	12534	-0.041	0.14	NO
42	ILK	ILK	ILK	12558	-0.042	0.15	NO
43	ELK1	ELK1	ELK1	12609	-0.043	0.16	NO
44	GSK3B	GSK3B	GSK3B	12703	-0.045	0.16	NO
45	AKT3	AKT3	AKT3	13287	-0.059	0.14	NO
46	MLH1	MLH1	MLH1	13350	-0.061	0.15	NO
47	CCND1	CCND1	CCND1	13448	-0.064	0.16	NO
48	NRAS	NRAS	NRAS	13630	-0.068	0.16	NO
49	PIK3CG	PIK3CG	PIK3CG	13807	-0.074	0.17	NO
50	CTNNA1	CTNNA1	CTNNA1	14155	-0.086	0.17	NO
51	BRAF	BRAF	BRAF	14910	-0.12	0.15	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 FATTY ACID METABOLISM.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FATTY ACID 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 ABC TRANSPORTERS

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	TGFA	TGFA	TGFA	428	0.48	0.081	YES
2	RXRG	RXRG	RXRG	740	0.39	0.15	YES
3	FHIT	FHIT	FHIT	811	0.38	0.23	YES
4	EGFR	EGFR	EGFR	1574	0.27	0.24	YES
5	PRKCA	PRKCA	PRKCA	1756	0.25	0.29	YES
6	PRKCB	PRKCB	PRKCB	1791	0.25	0.34	YES
7	PRKCG	PRKCG	PRKCG	1881	0.24	0.39	YES
8	ERBB2	ERBB2	ERBB2	3111	0.16	0.36	YES
9	FOXO3	FOXO3	FOXO3	3358	0.14	0.37	YES
10	EGF	EGF	EGF	3676	0.13	0.38	YES
11	RASSF5	RASSF5	RASSF5	3881	0.12	0.4	YES
12	PLCG1	PLCG1	PLCG1	4157	0.11	0.4	YES
13	RARB	RARB	RARB	4859	0.089	0.38	YES
14	PIK3R3	PIK3R3	PIK3R3	4935	0.087	0.4	YES
15	SOS1	SOS1	SOS1	5097	0.083	0.41	YES
16	RXRB	RXRB	RXRB	5702	0.069	0.39	NO
17	PIK3R5	PIK3R5	PIK3R5	5842	0.065	0.4	NO
18	PIK3CD	PIK3CD	PIK3CD	6610	0.05	0.36	NO
19	MAP2K2	MAP2K2	MAP2K2	6644	0.05	0.37	NO
20	TP53	TP53	TP53	7290	0.038	0.34	NO
21	PIK3R2	PIK3R2	PIK3R2	7909	0.028	0.31	NO
22	STK4	STK4	STK4	8029	0.027	0.31	NO
23	SOS2	SOS2	SOS2	8082	0.026	0.32	NO
24	PLCG2	PLCG2	PLCG2	8538	0.02	0.29	NO
25	CDKN2A	CDKN2A	CDKN2A	8662	0.018	0.29	NO
26	RB1	RB1	RB1	8695	0.017	0.29	NO
27	RASSF1	RASSF1	RASSF1	8705	0.017	0.3	NO
28	RXRA	RXRA	RXRA	9146	0.011	0.27	NO
29	BAD	BAD	BAD	9492	0.0065	0.26	NO
30	HRAS	HRAS	HRAS	9645	0.0042	0.25	NO
31	E2F3	E2F3	E2F3	9712	0.0032	0.24	NO
32	AKT2	AKT2	AKT2	9898	0.0008	0.23	NO
33	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.22	NO
34	PDPK1	PDPK1	PDPK1	10075	-0.0015	0.22	NO
35	MAPK1	MAPK1	MAPK1	10098	-0.002	0.22	NO
36	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.21	NO
37	PIK3R1	PIK3R1	PIK3R1	10385	-0.0058	0.21	NO
38	CASP9	CASP9	CASP9	10548	-0.008	0.2	NO
39	PIK3CB	PIK3CB	PIK3CB	11003	-0.015	0.18	NO
40	RAF1	RAF1	RAF1	11534	-0.023	0.15	NO
41	PIK3CA	PIK3CA	PIK3CA	11608	-0.024	0.16	NO
42	KRAS	KRAS	KRAS	11611	-0.024	0.16	NO
43	GRB2	GRB2	GRB2	11623	-0.024	0.16	NO
44	ARAF	ARAF	ARAF	11932	-0.03	0.15	NO
45	AKT1	AKT1	AKT1	11936	-0.03	0.16	NO
46	CDK4	CDK4	CDK4	13237	-0.057	0.098	NO
47	AKT3	AKT3	AKT3	13287	-0.059	0.11	NO
48	CCND1	CCND1	CCND1	13448	-0.064	0.11	NO
49	NRAS	NRAS	NRAS	13630	-0.068	0.12	NO
50	PIK3CG	PIK3CG	PIK3CG	13807	-0.074	0.12	NO
51	CDK6	CDK6	CDK6	14411	-0.096	0.11	NO
52	BRAF	BRAF	BRAF	14910	-0.12	0.11	NO
53	E2F2	E2F2	E2F2	16069	-0.2	0.085	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: KEGG ABC TRANSPORTERS.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ABC TRANSPORTERS, 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 CARDIAC MUSCLE CONTRACTION

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	KCNB1	KCNB1	KCNB1	189	0.6	0.11	YES
2	CACNA1A	CACNA1A	CACNA1A	360	0.51	0.2	YES
3	GRM4	GRM4	GRM4	440	0.48	0.29	YES
4	TAS2R10	TAS2R10	TAS2R10	1276	0.3	0.3	YES
5	TAS1R3	TAS1R3	TAS1R3	1689	0.26	0.33	YES
6	TAS2R43	TAS2R43	TAS2R43	2015	0.23	0.36	YES
7	SCNN1A	SCNN1A	SCNN1A	2116	0.22	0.4	YES
8	TAS2R20	TAS2R20	TAS2R20	2170	0.22	0.44	YES
9	SCNN1B	SCNN1B	SCNN1B	2426	0.2	0.46	YES
10	GNB3	GNB3	GNB3	2490	0.2	0.5	YES
11	TRPM5	TRPM5	TRPM5	2736	0.18	0.52	YES
12	TAS2R5	TAS2R5	TAS2R5	2757	0.18	0.55	YES
13	CACNA1B	CACNA1B	CACNA1B	3089	0.16	0.56	YES
14	GNG13	GNG13	GNG13	3698	0.13	0.56	YES
15	TAS1R1	TAS1R1	TAS1R1	3794	0.12	0.57	YES
16	TAS2R4	TAS2R4	TAS2R4	4253	0.11	0.57	YES
17	GNG3	GNG3	GNG3	4332	0.1	0.58	YES
18	SCNN1G	SCNN1G	SCNN1G	5120	0.083	0.56	NO
19	ADCY6	ADCY6	ADCY6	5273	0.079	0.56	NO
20	ADCY4	ADCY4	ADCY4	5559	0.072	0.56	NO
21	TAS2R19	TAS2R19	TAS2R19	6096	0.06	0.54	NO
22	TAS2R31	TAS2R31	TAS2R31	6957	0.044	0.5	NO
23	TAS2R46	TAS2R46	TAS2R46	7024	0.042	0.51	NO
24	GNAS	GNAS	GNAS	7508	0.035	0.49	NO
25	PRKACA	PRKACA	PRKACA	8450	0.021	0.44	NO
26	TAS2R14	TAS2R14	TAS2R14	8751	0.017	0.42	NO
27	ITPR3	ITPR3	ITPR3	8960	0.014	0.41	NO
28	PLCB2	PLCB2	PLCB2	9826	0.0019	0.36	NO
29	PRKACB	PRKACB	PRKACB	10030	-0.00093	0.35	NO
30	PRKX	PRKX	PRKX	12290	-0.036	0.23	NO
31	GNB1	GNB1	GNB1	12453	-0.039	0.23	NO
32	TAS2R13	TAS2R13	TAS2R13	12931	-0.05	0.21	NO
33	ACCN1	ACCN1	ACCN1	14871	-0.12	0.12	NO
34	PDE1A	PDE1A	PDE1A	15400	-0.14	0.12	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: KEGG CARDIAC MUSCLE CONTRACTION.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CARDIAC 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 WNT SIGNALING 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	CACNA2D2	CACNA2D2	CACNA2D2	435	0.48	0.037	YES
2	ATP1B2	ATP1B2	ATP1B2	534	0.44	0.089	YES
3	COX4I2	COX4I2	COX4I2	619	0.42	0.14	YES
4	TNNT2	TNNT2	TNNT2	947	0.36	0.17	YES
5	CACNA2D3	CACNA2D3	CACNA2D3	1163	0.32	0.2	YES
6	CACNG2	CACNG2	CACNG2	1238	0.31	0.23	YES
7	MYL3	MYL3	MYL3	1258	0.31	0.27	YES
8	CACNG3	CACNG3	CACNG3	1332	0.3	0.3	YES
9	TNNC1	TNNC1	TNNC1	1687	0.26	0.32	YES
10	CACNA1F	CACNA1F	CACNA1F	1744	0.26	0.35	YES
11	CACNA1D	CACNA1D	CACNA1D	2019	0.23	0.36	YES
12	COX6B2	COX6B2	COX6B2	2105	0.22	0.39	YES
13	CACNG5	CACNG5	CACNG5	2146	0.22	0.41	YES
14	MYL2	MYL2	MYL2	2253	0.21	0.43	YES
15	CACNB1	CACNB1	CACNB1	2910	0.17	0.42	NO
16	ATP1A3	ATP1A3	ATP1A3	3657	0.13	0.39	NO
17	CACNB2	CACNB2	CACNB2	4065	0.11	0.38	NO
18	CACNA2D4	CACNA2D4	CACNA2D4	4568	0.096	0.37	NO
19	UQCRB	UQCRB	UQCRB	5266	0.079	0.34	NO
20	CACNA1C	CACNA1C	CACNA1C	5662	0.07	0.32	NO
21	COX7C	COX7C	COX7C	6439	0.053	0.29	NO
22	ATP1A2	ATP1A2	ATP1A2	6527	0.052	0.29	NO
23	COX6B1	COX6B1	COX6B1	7319	0.038	0.25	NO
24	UQCR10	UQCR10	UQCR10	7533	0.034	0.24	NO
25	COX4I1	COX4I1	COX4I1	7547	0.034	0.24	NO
26	UQCR11	UQCR11	UQCR11	8065	0.026	0.22	NO
27	UQCRH	UQCRH	UQCRH	8081	0.026	0.22	NO
28	SLC9A1	SLC9A1	SLC9A1	8290	0.023	0.21	NO
29	UQCRHL	UQCRHL	UQCRHL	8828	0.016	0.18	NO
30	COX7A2L	COX7A2L	COX7A2L	8841	0.015	0.18	NO
31	COX6A1	COX6A1	COX6A1	9427	0.0074	0.15	NO
32	UQCRQ	UQCRQ	UQCRQ	9573	0.0056	0.14	NO
33	ATP1B1	ATP1B1	ATP1B1	9649	0.0041	0.14	NO
34	COX6C	COX6C	COX6C	9676	0.0038	0.14	NO
35	MYH7	MYH7	MYH7	10255	-0.0039	0.11	NO
36	UQCRFS1	UQCRFS1	UQCRFS1	10700	-0.01	0.082	NO
37	TPM3	TPM3	TPM3	10925	-0.014	0.072	NO
38	UQCRC1	UQCRC1	UQCRC1	11045	-0.015	0.067	NO
39	CYC1	CYC1	CYC1	11421	-0.021	0.048	NO
40	COX5B	COX5B	COX5B	11614	-0.024	0.04	NO
41	COX7B	COX7B	COX7B	11783	-0.027	0.034	NO
42	COX5A	COX5A	COX5A	12072	-0.032	0.022	NO
43	FXYD2	FXYD2	FXYD2	12272	-0.036	0.015	NO
44	CACNB4	CACNB4	CACNB4	12546	-0.041	0.0047	NO
45	COX8A	COX8A	COX8A	12693	-0.044	0.0021	NO
46	ATP2A2	ATP2A2	ATP2A2	12853	-0.048	-0.0008	NO
47	COX7A1	COX7A1	COX7A1	12896	-0.049	0.0031	NO
48	RYR2	RYR2	RYR2	13060	-0.052	0.00059	NO
49	ATP1B3	ATP1B3	ATP1B3	13103	-0.054	0.0051	NO
50	SLC9A6	SLC9A6	SLC9A6	13136	-0.054	0.01	NO
51	CACNB3	CACNB3	CACNB3	13400	-0.062	0.0033	NO
52	COX7A2	COX7A2	COX7A2	13609	-0.068	0.00025	NO
53	TPM4	TPM4	TPM4	13617	-0.068	0.0087	NO
54	ATP1A1	ATP1A1	ATP1A1	13789	-0.073	0.0084	NO
55	COX8C	COX8C	COX8C	15105	-0.13	-0.05	NO
56	TPM2	TPM2	TPM2	15273	-0.14	-0.042	NO
57	ATP1A4	ATP1A4	ATP1A4	15291	-0.14	-0.025	NO
58	CACNA2D1	CACNA2D1	CACNA2D1	15547	-0.16	-0.02	NO
59	TPM1	TPM1	TPM1	15589	-0.16	-0.0014	NO
60	MYH6	MYH6	MYH6	15815	-0.18	0.0085	NO
61	SLC8A1	SLC8A1	SLC8A1	15867	-0.18	0.029	NO
62	ACTC1	ACTC1	ACTC1	16494	-0.25	0.025	NO
63	CACNG4	CACNG4	CACNG4	16694	-0.28	0.05	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: KEGG WNT SIGNALING PATHWAY.

Figure S36. 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 CELL ADHESION MOLECULES CAMS

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	FLT3	FLT3	FLT3	67	0.77	0.16	YES
2	TCF7	TCF7	TCF7	389	0.49	0.24	YES
3	ZBTB16	ZBTB16	ZBTB16	988	0.35	0.28	YES
4	KIT	KIT	KIT	1291	0.3	0.32	YES
5	TCF7L1	TCF7L1	TCF7L1	1795	0.25	0.34	YES
6	LEF1	LEF1	LEF1	2274	0.21	0.36	YES
7	PIK3R3	PIK3R3	PIK3R3	4935	0.087	0.23	NO
8	IKBKB	IKBKB	IKBKB	5046	0.085	0.24	NO
9	SOS1	SOS1	SOS1	5097	0.083	0.25	NO
10	RARA	RARA	RARA	5450	0.075	0.25	NO
11	TCF7L2	TCF7L2	TCF7L2	5527	0.073	0.26	NO
12	PIK3R5	PIK3R5	PIK3R5	5842	0.065	0.25	NO
13	PIK3CD	PIK3CD	PIK3CD	6610	0.05	0.22	NO
14	MAP2K2	MAP2K2	MAP2K2	6644	0.05	0.23	NO
15	RPS6KB1	RPS6KB1	RPS6KB1	7296	0.038	0.2	NO
16	MYC	MYC	MYC	7762	0.031	0.18	NO
17	PIK3R2	PIK3R2	PIK3R2	7909	0.028	0.18	NO
18	SOS2	SOS2	SOS2	8082	0.026	0.17	NO
19	STAT5B	STAT5B	STAT5B	8460	0.021	0.15	NO
20	MTOR	MTOR	MTOR	9106	0.012	0.12	NO
21	BAD	BAD	BAD	9492	0.0065	0.098	NO
22	STAT5A	STAT5A	STAT5A	9532	0.0061	0.098	NO
23	HRAS	HRAS	HRAS	9645	0.0042	0.092	NO
24	RUNX1T1	RUNX1T1	RUNX1T1	9870	0.0012	0.079	NO
25	AKT2	AKT2	AKT2	9898	0.0008	0.078	NO
26	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.069	NO
27	MAPK1	MAPK1	MAPK1	10098	-0.002	0.067	NO
28	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.054	NO
29	PIK3R1	PIK3R1	PIK3R1	10385	-0.0058	0.053	NO
30	IKBKG	IKBKG	IKBKG	10455	-0.0066	0.051	NO
31	PML	PML	PML	10563	-0.0081	0.046	NO
32	RPS6KB2	RPS6KB2	RPS6KB2	10833	-0.012	0.034	NO
33	RELA	RELA	RELA	10870	-0.012	0.034	NO
34	PIK3CB	PIK3CB	PIK3CB	11003	-0.015	0.03	NO
35	RAF1	RAF1	RAF1	11534	-0.023	0.0039	NO
36	PIK3CA	PIK3CA	PIK3CA	11608	-0.024	0.0046	NO
37	KRAS	KRAS	KRAS	11611	-0.024	0.0094	NO
38	GRB2	GRB2	GRB2	11623	-0.024	0.014	NO
39	ARAF	ARAF	ARAF	11932	-0.03	0.0023	NO
40	AKT1	AKT1	AKT1	11936	-0.03	0.0082	NO
41	NFKB1	NFKB1	NFKB1	12109	-0.033	0.0052	NO
42	JUP	JUP	JUP	12874	-0.048	-0.028	NO
43	SPI1	SPI1	SPI1	13214	-0.057	-0.036	NO
44	AKT3	AKT3	AKT3	13287	-0.059	-0.028	NO
45	CCND1	CCND1	CCND1	13448	-0.064	-0.024	NO
46	CCNA1	CCNA1	CCNA1	13515	-0.065	-0.015	NO
47	NRAS	NRAS	NRAS	13630	-0.068	-0.0071	NO
48	PIK3CG	PIK3CG	PIK3CG	13807	-0.074	-0.002	NO
49	RUNX1	RUNX1	RUNX1	14013	-0.08	0.0028	NO
50	CHUK	CHUK	CHUK	14560	-0.1	-0.0074	NO
51	CEBPA	CEBPA	CEBPA	14565	-0.1	0.014	NO
52	STAT3	STAT3	STAT3	14838	-0.12	0.022	NO
53	BRAF	BRAF	BRAF	14910	-0.12	0.042	NO
54	PIM1	PIM1	PIM1	15312	-0.14	0.048	NO
55	PIM2	PIM2	PIM2	15605	-0.16	0.064	NO
56	EIF4EBP1	EIF4EBP1	EIF4EBP1	16394	-0.23	0.067	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: KEGG CELL ADHESION MOLECULES CAMS.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CELL ADHESION MOLECULES CAMS, 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 INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION

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	ADCY5	ADCY5	ADCY5	43	0.83	0.056	YES
2	GNAO1	GNAO1	GNAO1	169	0.62	0.093	YES
3	TCF7	TCF7	TCF7	389	0.49	0.12	YES
4	CAMK2B	CAMK2B	CAMK2B	426	0.48	0.15	YES
5	EDNRB	EDNRB	EDNRB	484	0.46	0.18	YES
6	WNT10B	WNT10B	WNT10B	572	0.43	0.2	YES
7	CREB3L3	CREB3L3	CREB3L3	733	0.4	0.22	YES
8	CALML6	CALML6	CALML6	790	0.38	0.24	YES
9	WNT6	WNT6	WNT6	927	0.36	0.26	YES
10	WNT7A	WNT7A	WNT7A	1136	0.32	0.27	YES
11	WNT16	WNT16	WNT16	1168	0.32	0.29	YES
12	KIT	KIT	KIT	1291	0.3	0.31	YES
13	FZD8	FZD8	FZD8	1324	0.3	0.33	YES
14	ADCY1	ADCY1	ADCY1	1446	0.29	0.34	YES
15	PLCB4	PLCB4	PLCB4	1556	0.27	0.35	YES
16	FZD7	FZD7	FZD7	1614	0.27	0.37	YES
17	WNT1	WNT1	WNT1	1627	0.27	0.39	YES
18	PRKCA	PRKCA	PRKCA	1756	0.25	0.4	YES
19	PRKCB	PRKCB	PRKCB	1791	0.25	0.41	YES
20	TCF7L1	TCF7L1	TCF7L1	1795	0.25	0.43	YES
21	PRKCG	PRKCG	PRKCG	1881	0.24	0.44	YES
22	FZD10	FZD10	FZD10	1958	0.24	0.46	YES
23	LEF1	LEF1	LEF1	2274	0.21	0.45	NO
24	WNT5B	WNT5B	WNT5B	2643	0.18	0.44	NO
25	CREB3L2	CREB3L2	CREB3L2	2929	0.17	0.44	NO
26	EDN1	EDN1	EDN1	2976	0.16	0.45	NO
27	KITLG	KITLG	KITLG	3107	0.16	0.45	NO
28	ADCY9	ADCY9	ADCY9	3994	0.12	0.41	NO
29	CREB3L4	CREB3L4	CREB3L4	4209	0.11	0.4	NO
30	WNT4	WNT4	WNT4	4278	0.1	0.41	NO
31	MC1R	MC1R	MC1R	4343	0.1	0.41	NO
32	CALML5	CALML5	CALML5	4345	0.1	0.42	NO
33	CAMK2D	CAMK2D	CAMK2D	4515	0.098	0.42	NO
34	WNT8B	WNT8B	WNT8B	4587	0.096	0.42	NO
35	CREBBP	CREBBP	CREBBP	4729	0.092	0.42	NO
36	CAMK2G	CAMK2G	CAMK2G	4970	0.087	0.41	NO
37	DVL1	DVL1	DVL1	5125	0.083	0.41	NO
38	ADCY6	ADCY6	ADCY6	5273	0.079	0.4	NO
39	PLCB1	PLCB1	PLCB1	5417	0.075	0.4	NO
40	TCF7L2	TCF7L2	TCF7L2	5527	0.073	0.4	NO
41	ADCY4	ADCY4	ADCY4	5559	0.072	0.4	NO
42	GNAI1	GNAI1	GNAI1	5773	0.067	0.4	NO
43	DVL2	DVL2	DVL2	6435	0.053	0.36	NO
44	MAP2K2	MAP2K2	MAP2K2	6644	0.05	0.35	NO
45	FZD4	FZD4	FZD4	6818	0.046	0.35	NO
46	WNT9A	WNT9A	WNT9A	6842	0.046	0.35	NO
47	ADCY7	ADCY7	ADCY7	7462	0.036	0.32	NO
48	GNAS	GNAS	GNAS	7508	0.035	0.32	NO
49	PRKACA	PRKACA	PRKACA	8450	0.021	0.26	NO
50	EP300	EP300	EP300	8466	0.021	0.26	NO
51	CREB1	CREB1	CREB1	8961	0.014	0.24	NO
52	CALML3	CALML3	CALML3	9268	0.0095	0.22	NO
53	HRAS	HRAS	HRAS	9645	0.0042	0.2	NO
54	PLCB2	PLCB2	PLCB2	9826	0.0019	0.19	NO
55	PRKACB	PRKACB	PRKACB	10030	-0.00093	0.18	NO
56	MAP2K1	MAP2K1	MAP2K1	10055	-0.0013	0.18	NO
57	MAPK1	MAPK1	MAPK1	10098	-0.002	0.17	NO
58	WNT3	WNT3	WNT3	10155	-0.0026	0.17	NO
59	CALM3	CALM3	CALM3	10189	-0.0031	0.17	NO
60	WNT2B	WNT2B	WNT2B	10225	-0.0036	0.17	NO
61	MAPK3	MAPK3	MAPK3	10359	-0.0055	0.16	NO
62	POMC	POMC	POMC	10361	-0.0055	0.16	NO
63	DVL3	DVL3	DVL3	10539	-0.0078	0.15	NO
64	CALM1	CALM1	CALM1	10694	-0.01	0.14	NO
65	CREB3	CREB3	CREB3	10849	-0.012	0.14	NO
66	ADCY2	ADCY2	ADCY2	10901	-0.013	0.13	NO
67	FZD3	FZD3	FZD3	10968	-0.014	0.13	NO
68	WNT11	WNT11	WNT11	11159	-0.017	0.12	NO
69	GNAI2	GNAI2	GNAI2	11508	-0.022	0.1	NO
70	RAF1	RAF1	RAF1	11534	-0.023	0.1	NO
71	KRAS	KRAS	KRAS	11611	-0.024	0.1	NO
72	FZD6	FZD6	FZD6	11618	-0.024	0.1	NO
73	PRKX	PRKX	PRKX	12290	-0.036	0.065	NO
74	CTNNB1	CTNNB1	CTNNB1	12534	-0.041	0.054	NO
75	CALM2	CALM2	CALM2	12587	-0.042	0.054	NO
76	GSK3B	GSK3B	GSK3B	12703	-0.045	0.051	NO
77	WNT10A	WNT10A	WNT10A	13038	-0.052	0.035	NO
78	NRAS	NRAS	NRAS	13630	-0.068	0.0062	NO
79	PLCB3	PLCB3	PLCB3	13754	-0.072	0.0042	NO
80	GNAQ	GNAQ	GNAQ	14066	-0.082	-0.0078	NO
81	FZD9	FZD9	FZD9	14185	-0.087	-0.0084	NO
82	GNAI3	GNAI3	GNAI3	14273	-0.091	-0.007	NO
83	FZD2	FZD2	FZD2	14507	-0.1	-0.013	NO
84	TYRP1	TYRP1	TYRP1	14600	-0.1	-0.011	NO
85	ASIP	ASIP	ASIP	14907	-0.12	-0.02	NO
86	WNT7B	WNT7B	WNT7B	15509	-0.15	-0.044	NO
87	WNT5A	WNT5A	WNT5A	15692	-0.17	-0.043	NO
88	MITF	MITF	MITF	16364	-0.23	-0.065	NO
89	FZD5	FZD5	FZD5	16411	-0.24	-0.051	NO
90	FZD1	FZD1	FZD1	16707	-0.28	-0.048	NO
91	CAMK2A	CAMK2A	CAMK2A	17098	-0.37	-0.045	NO
92	CREB3L1	CREB3L1	CREB3L1	17327	-0.47	-0.025	NO
93	WNT2	WNT2	WNT2	17432	-0.54	0.0073	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: KEGG INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION, 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.v3.0-2.symbols.gmt
Expression data file = DLBC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = DLBC-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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