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

Head and Neck Squamous Cell Carcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

doi:10.7908/C1959GJZ

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 HNSC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1959GJZ

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 HNSC-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: 192
Number of samples: 520
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 144
pheno.type: 2 - 3 :[ clus2 ] 214
pheno.type: 3 - 3 :[ clus3 ] 162

For the expression subtypes of 18378 genes in 521 samples, GSEA found enriched gene sets in each cluster using 520 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA CARM ER PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA FMLP PATHWAY

And common core enriched genes are PPP1R12B, ACTA1, ARHGAP6, MYL2, MYLK, PIP5K1B, ACTN1, ACTN2, ACTN3, CAV1

clus2

Top enriched gene sets are BIOCARTA CHREBP2 PATHWAY, BIOCARTA WNT PATHWAY, KEGG FATTY ACID METABOLISM, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION, KEGG SELENOAMINO ACID METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, KEGG BUTANOATE METABOLISM

And common core enriched genes are UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2B15

clus3

Top enriched gene sets are BIOCARTA ERK PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA PYK2 PATHWAY, BIOCARTA IL1R PATHWAY, KEGG PYRIMIDINE METABOLISM, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA POLYMERASE

And common core enriched genes are IFNG, POMP, PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1

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 NO1 PATHWAY	28	genes.ES.table	0.75	1.8	0	0.032	0.29	0.25	0.061	0.24	0	0
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.73	2	0	0.012	0.059	0.26	0.084	0.24	0	0
BIOCARTA ALK PATHWAY	34	genes.ES.table	0.64	1.8	0	0.032	0.29	0.44	0.2	0.35	0	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.58	2.1	0.0019	0.014	0.027	0.28	0.22	0.22	0	0.002
BIOCARTA BIOPEPTIDES PATHWAY	40	genes.ES.table	0.63	2.1	0	0.0093	0.028	0.1	0.013	0.099	0	0
BIOCARTA CARM ER PATHWAY	34	genes.ES.table	0.43	1.5	0.072	0.13	0.89	0.24	0.24	0.18	0.091	0
BIOCARTA HDAC PATHWAY	27	genes.ES.table	0.64	1.8	0	0.033	0.28	0.52	0.27	0.38	0	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.57	1.8	0.0082	0.034	0.32	0.4	0.26	0.3	0	0
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.46	1.5	0.069	0.12	0.86	0.26	0.22	0.2	0.08	0
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.4	1.3	0.18	0.24	0.98	0.29	0.24	0.22	0.2	0.002

genes ES table in pathway: BIOCARTA NO1 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	MYL2	MYL2	MYL2	27	1.5	0.44	YES
2	ARHGAP6	ARHGAP6	ARHGAP6	413	0.43	0.54	YES
3	PPP1R12B	PPP1R12B	PPP1R12B	1332	0.23	0.55	YES
4	PIP5K1B	PIP5K1B	PIP5K1B	1692	0.2	0.59	YES
5	MYLK	MYLK	MYLK	1784	0.19	0.64	YES
6	VCL	VCL	VCL	3822	0.082	0.55	NO
7	ARPC1B	ARPC1B	ARPC1B	4005	0.076	0.56	NO
8	ARHGAP1	ARHGAP1	ARHGAP1	4329	0.066	0.56	NO
9	OPHN1	OPHN1	OPHN1	4937	0.052	0.55	NO
10	LIMK1	LIMK1	LIMK1	5215	0.046	0.54	NO
11	GSN	GSN	GSN	5405	0.042	0.55	NO
12	ROCK1	ROCK1	ROCK1	5448	0.042	0.56	NO
13	SRC	SRC	SRC	5662	0.038	0.55	NO
14	PFN1	PFN1	PFN1	6036	0.033	0.54	NO
15	CFL1	CFL1	CFL1	6213	0.03	0.54	NO
16	ACTR2	ACTR2	ACTR2	6612	0.024	0.53	NO
17	ARHGAP5	ARHGAP5	ARHGAP5	6772	0.022	0.52	NO
18	DIAPH1	DIAPH1	DIAPH1	7177	0.018	0.51	NO
19	RHOA	RHOA	RHOA	7290	0.016	0.51	NO
20	ARHGEF1	ARHGEF1	ARHGEF1	7380	0.016	0.51	NO
21	ARPC2	ARPC2	ARPC2	7838	0.011	0.48	NO
22	ACTR3	ACTR3	ACTR3	8431	0.0048	0.45	NO
23	PIP5K1A	PIP5K1A	PIP5K1A	8745	0.0017	0.44	NO
24	ARHGEF11	ARHGEF11	ARHGEF11	9077	-0.0013	0.42	NO
25	ARPC4	ARPC4	ARPC4	9109	-0.0017	0.42	NO
26	ARPC1A	ARPC1A	ARPC1A	10262	-0.012	0.36	NO
27	ARPC5	ARPC5	ARPC5	11350	-0.022	0.31	NO
28	ARPC3	ARPC3	ARPC3	11460	-0.024	0.31	NO
29	BAIAP2	BAIAP2	BAIAP2	13640	-0.049	0.2	NO
30	ARHGEF5	ARHGEF5	ARHGEF5	14645	-0.065	0.17	NO
31	ARHGAP4	ARHGAP4	ARHGAP4	16608	-0.13	0.096	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 NO1 PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 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 AGR 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	ACTN2	ACTN2	ACTN2	21	1.5	0.26	YES
2	ACTA1	ACTA1	ACTA1	23	1.5	0.52	YES
3	ACTN3	ACTN3	ACTN3	433	0.42	0.57	YES
4	TNS1	TNS1	TNS1	883	0.29	0.6	YES
5	ITGA1	ITGA1	ITGA1	1307	0.23	0.61	YES
6	PPP1R12B	PPP1R12B	PPP1R12B	1332	0.23	0.65	YES
7	CAV1	CAV1	CAV1	1791	0.19	0.66	YES
8	ACTN1	ACTN1	ACTN1	2421	0.14	0.65	YES
9	ITGB1	ITGB1	ITGB1	2836	0.12	0.65	YES
10	RAPGEF1	RAPGEF1	RAPGEF1	3030	0.11	0.65	YES
11	FYN	FYN	FYN	3039	0.11	0.67	YES
12	PXN	PXN	PXN	3089	0.11	0.69	YES
13	VCL	VCL	VCL	3822	0.082	0.66	NO
14	MAPK8	MAPK8	MAPK8	4036	0.075	0.66	NO
15	BCAR1	BCAR1	BCAR1	4296	0.067	0.66	NO
16	ZYX	ZYX	ZYX	4367	0.065	0.67	NO
17	SHC1	SHC1	SHC1	4745	0.056	0.66	NO
18	PTK2	PTK2	PTK2	5277	0.045	0.64	NO
19	RAP1A	RAP1A	RAP1A	5378	0.043	0.64	NO
20	ROCK1	ROCK1	ROCK1	5448	0.042	0.64	NO
21	SRC	SRC	SRC	5662	0.038	0.64	NO
22	JUN	JUN	JUN	5847	0.035	0.63	NO
23	MAPK1	MAPK1	MAPK1	7096	0.019	0.57	NO
24	RHOA	RHOA	RHOA	7290	0.016	0.56	NO
25	SOS1	SOS1	SOS1	7663	0.013	0.54	NO
26	CRKL	CRKL	CRKL	7686	0.012	0.54	NO
27	MAP2K1	MAP2K1	MAP2K1	8211	0.0071	0.51	NO
28	CAPN1	CAPN1	CAPN1	8817	0.001	0.48	NO
29	CAPNS1	CAPNS1	CAPNS1	8972	-0.00034	0.47	NO
30	GRB2	GRB2	GRB2	9523	-0.0055	0.44	NO
31	HRAS	HRAS	HRAS	10029	-0.0099	0.42	NO
32	RAF1	RAF1	RAF1	10715	-0.016	0.38	NO
33	BCR	BCR	BCR	11943	-0.029	0.32	NO
34	MAPK3	MAPK3	MAPK3	12238	-0.032	0.31	NO
35	MAP2K2	MAP2K2	MAP2K2	12299	-0.033	0.31	NO
36	CSK	CSK	CSK	12816	-0.038	0.29	NO
37	CAPNS2	CAPNS2	CAPNS2	14593	-0.064	0.21	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 AGR PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AGR 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 ALK 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	HSPB2	HSPB2	HSPB2	176	0.79	0.21	YES
2	MEF2C	MEF2C	MEF2C	207	0.7	0.41	YES
3	TGFB3	TGFB3	TGFB3	743	0.32	0.47	YES
4	TGFB2	TGFB2	TGFB2	1098	0.26	0.52	YES
5	ATF2	ATF2	ATF2	3433	0.095	0.42	NO
6	TGFBR1	TGFBR1	TGFBR1	3516	0.092	0.45	NO
7	MEF2D	MEF2D	MEF2D	3558	0.091	0.47	NO
8	RAPGEF2	RAPGEF2	RAPGEF2	3679	0.087	0.49	NO
9	MEF2A	MEF2A	MEF2A	3907	0.079	0.5	NO
10	TGFB1	TGFB1	TGFB1	4308	0.067	0.49	NO
11	STAT1	STAT1	STAT1	4431	0.063	0.5	NO
12	SHC1	SHC1	SHC1	4745	0.056	0.5	NO
13	MAP3K7	MAP3K7	MAP3K7	7673	0.012	0.35	NO
14	ELK1	ELK1	ELK1	7699	0.012	0.35	NO
15	CDC42	CDC42	CDC42	7701	0.012	0.35	NO
16	CREB1	CREB1	CREB1	7720	0.012	0.36	NO
17	MAP2K4	MAP2K4	MAP2K4	7787	0.011	0.36	NO
18	MAPKAPK2	MAPKAPK2	MAPKAPK2	7978	0.0094	0.35	NO
19	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	8169	0.0076	0.34	NO
20	MAP3K1	MAP3K1	MAP3K1	8199	0.0073	0.34	NO
21	MAPK14	MAPK14	MAPK14	8829	0.001	0.31	NO
22	RIPK1	RIPK1	RIPK1	8866	0.00062	0.3	NO
23	MKNK1	MKNK1	MKNK1	9066	-0.0013	0.29	NO
24	DAXX	DAXX	DAXX	9335	-0.0036	0.28	NO
25	GRB2	GRB2	GRB2	9523	-0.0055	0.27	NO
26	HRAS	HRAS	HRAS	10029	-0.0099	0.25	NO
27	MAX	MAX	MAX	10456	-0.014	0.23	NO
28	MYC	MYC	MYC	10473	-0.014	0.23	NO
29	MAPKAPK5	MAPKAPK5	MAPKAPK5	11631	-0.025	0.17	NO
30	RAC1	RAC1	RAC1	11810	-0.027	0.17	NO
31	TRADD	TRADD	TRADD	12692	-0.037	0.13	NO
32	DDIT3	DDIT3	DDIT3	12919	-0.04	0.13	NO
33	TRAF2	TRAF2	TRAF2	13831	-0.051	0.098	NO
34	MAP3K9	MAP3K9	MAP3K9	13990	-0.053	0.1	NO
35	MAP3K5	MAP3K5	MAP3K5	14205	-0.057	0.11	NO
36	RPS6KA5	RPS6KA5	RPS6KA5	14280	-0.058	0.12	NO
37	HSPB1	HSPB1	HSPB1	14376	-0.06	0.13	NO
38	MAP2K6	MAP2K6	MAP2K6	16679	-0.13	0.045	NO
39	PLA2G4A	PLA2G4A	PLA2G4A	17276	-0.17	0.059	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 ALK PATHWAY.

Figure S6. 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 AT1R PATHWAY

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	ACTA1	ACTA1	ACTA1	23	1.5	0.48	YES
2	PGR	PGR	PGR	435	0.42	0.59	YES
3	PRKACB	PRKACB	PRKACB	3285	0.1	0.46	NO
4	PAQR5	PAQR5	PAQR5	3910	0.079	0.45	NO
5	PRKAR2A	PRKAR2A	PRKAR2A	3922	0.079	0.48	NO
6	ARPC1B	ARPC1B	ARPC1B	4005	0.076	0.5	NO
7	PRKAR2B	PRKAR2B	PRKAR2B	4318	0.066	0.5	NO
8	SRC	SRC	SRC	5662	0.038	0.44	NO
9	GNB1	GNB1	GNB1	5805	0.036	0.44	NO
10	CAP1	CAP1	CAP1	5880	0.035	0.45	NO
11	PRKAR1A	PRKAR1A	PRKAR1A	5926	0.034	0.46	NO
12	ACTR2	ACTR2	ACTR2	6612	0.024	0.43	NO
13	PAQR7	PAQR7	PAQR7	6814	0.022	0.42	NO
14	GNAS	GNAS	GNAS	6865	0.021	0.43	NO
15	MAPK1	MAPK1	MAPK1	7096	0.019	0.42	NO
16	RPS6KA1	RPS6KA1	RPS6KA1	7131	0.018	0.42	NO
17	GNAI1	GNAI1	GNAI1	7163	0.018	0.43	NO
18	ARPC2	ARPC2	ARPC2	7838	0.011	0.4	NO
19	ACTR3	ACTR3	ACTR3	8431	0.0048	0.36	NO
20	ARPC4	ARPC4	ARPC4	9109	-0.0017	0.33	NO
21	HRAS	HRAS	HRAS	10029	-0.0099	0.28	NO
22	ARPC1A	ARPC1A	ARPC1A	10262	-0.012	0.27	NO
23	ARPC5	ARPC5	ARPC5	11350	-0.022	0.22	NO
24	ARPC3	ARPC3	ARPC3	11460	-0.024	0.22	NO
25	MAPK3	MAPK3	MAPK3	12238	-0.032	0.19	NO
26	PIN1	PIN1	PIN1	12372	-0.033	0.19	NO
27	PRKAR1B	PRKAR1B	PRKAR1B	12892	-0.039	0.18	NO
28	MYT1	MYT1	MYT1	14377	-0.06	0.11	NO
29	GNGT1	GNGT1	GNGT1	14607	-0.064	0.12	NO
30	CCNB1	CCNB1	CCNB1	14962	-0.072	0.12	NO
31	CDK1	CDK1	CDK1	15682	-0.092	0.12	NO
32	CDC25C	CDC25C	CDC25C	15913	-0.1	0.13	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: BIOCARTA AT1R PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R 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 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	AGT	AGT	AGT	234	0.63	0.26	YES
2	AGTR1	AGTR1	AGTR1	291	0.52	0.48	YES
3	PRKCA	PRKCA	PRKCA	1761	0.19	0.48	YES
4	PRKCB	PRKCB	PRKCB	3324	0.098	0.44	YES
5	ATF2	ATF2	ATF2	3433	0.095	0.47	YES
6	MEF2D	MEF2D	MEF2D	3558	0.091	0.5	YES
7	MEF2A	MEF2A	MEF2A	3907	0.079	0.52	YES
8	MAPK8	MAPK8	MAPK8	4036	0.075	0.55	YES
9	EGFR	EGFR	EGFR	4060	0.074	0.58	YES
10	SHC1	SHC1	SHC1	4745	0.056	0.56	NO
11	PTK2	PTK2	PTK2	5277	0.045	0.55	NO
12	SRC	SRC	SRC	5662	0.038	0.55	NO
13	JUN	JUN	JUN	5847	0.035	0.55	NO
14	CALM1	CALM1	CALM1	6049	0.032	0.56	NO
15	PTK2B	PTK2B	PTK2B	6162	0.031	0.56	NO
16	MAPK1	MAPK1	MAPK1	7096	0.019	0.52	NO
17	SOS1	SOS1	SOS1	7663	0.013	0.5	NO
18	ELK1	ELK1	ELK1	7699	0.012	0.5	NO
19	MAP2K4	MAP2K4	MAP2K4	7787	0.011	0.5	NO
20	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	8169	0.0076	0.48	NO
21	MAP3K1	MAP3K1	MAP3K1	8199	0.0073	0.48	NO
22	MAP2K1	MAP2K1	MAP2K1	8211	0.0071	0.48	NO
23	CALM3	CALM3	CALM3	8268	0.0065	0.48	NO
24	CALM2	CALM2	CALM2	8837	0.00092	0.45	NO
25	GRB2	GRB2	GRB2	9523	-0.0055	0.42	NO
26	GNAQ	GNAQ	GNAQ	9599	-0.0062	0.42	NO
27	HRAS	HRAS	HRAS	10029	-0.0099	0.4	NO
28	RAF1	RAF1	RAF1	10715	-0.016	0.37	NO
29	PAK1	PAK1	PAK1	11209	-0.021	0.35	NO
30	RAC1	RAC1	RAC1	11810	-0.027	0.33	NO
31	MAPK3	MAPK3	MAPK3	12238	-0.032	0.32	NO
32	MAP2K2	MAP2K2	MAP2K2	12299	-0.033	0.33	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: BIOCARTA BIOPEPTIDES PATHWAY.

Figure S10. 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 CARM ER PATHWAY

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	CAV3	CAV3	CAV3	13	1.6	0.046	YES
2	MYLPF	MYLPF	MYLPF	20	1.6	0.091	YES
3	ACTN2	ACTN2	ACTN2	21	1.5	0.14	YES
4	MYL2	MYL2	MYL2	27	1.5	0.18	YES
5	MYLK2	MYLK2	MYLK2	127	0.97	0.2	YES
6	FLNC	FLNC	FLNC	148	0.87	0.23	YES
7	THBS4	THBS4	THBS4	150	0.86	0.25	YES
8	MYLK3	MYLK3	MYLK3	204	0.71	0.27	YES
9	ITGA7	ITGA7	ITGA7	213	0.69	0.29	YES
10	EGF	EGF	EGF	350	0.46	0.3	YES
11	LAMA2	LAMA2	LAMA2	355	0.46	0.31	YES
12	IGF1	IGF1	IGF1	393	0.44	0.32	YES
13	ACTN3	ACTN3	ACTN3	433	0.42	0.33	YES
14	TNN	TNN	TNN	460	0.41	0.34	YES
15	RELN	RELN	RELN	498	0.4	0.35	YES
16	ITGB3	ITGB3	ITGB3	499	0.39	0.36	YES
17	COL11A1	COL11A1	COL11A1	574	0.37	0.37	YES
18	FN1	FN1	FN1	691	0.33	0.37	YES
19	ITGA10	ITGA10	ITGA10	696	0.33	0.38	YES
20	THBS2	THBS2	THBS2	728	0.32	0.39	YES
21	ITGA9	ITGA9	ITGA9	760	0.32	0.4	YES
22	ITGA11	ITGA11	ITGA11	776	0.31	0.4	YES
23	TNXB	TNXB	TNXB	788	0.31	0.41	YES
24	COMP	COMP	COMP	790	0.31	0.42	YES
25	VEGFC	VEGFC	VEGFC	809	0.3	0.43	YES
26	COL5A1	COL5A1	COL5A1	849	0.3	0.44	YES
27	COL4A6	COL4A6	COL4A6	852	0.3	0.44	YES
28	COL5A2	COL5A2	COL5A2	868	0.3	0.45	YES
29	RASGRF1	RASGRF1	RASGRF1	955	0.28	0.46	YES
30	ITGA8	ITGA8	ITGA8	1080	0.26	0.46	YES
31	COL3A1	COL3A1	COL3A1	1082	0.26	0.46	YES
32	COL6A3	COL6A3	COL6A3	1090	0.26	0.47	YES
33	FLT4	FLT4	FLT4	1120	0.26	0.48	YES
34	COL5A3	COL5A3	COL5A3	1157	0.25	0.48	YES
35	COL1A2	COL1A2	COL1A2	1162	0.25	0.49	YES
36	TNC	TNC	TNC	1206	0.24	0.49	YES
37	COL1A1	COL1A1	COL1A1	1214	0.24	0.5	YES
38	PDGFC	PDGFC	PDGFC	1273	0.24	0.5	YES
39	THBS1	THBS1	THBS1	1291	0.24	0.51	YES
40	PDGFRA	PDGFRA	PDGFRA	1300	0.23	0.52	YES
41	ITGA1	ITGA1	ITGA1	1307	0.23	0.52	YES
42	PDGFRB	PDGFRB	PDGFRB	1311	0.23	0.53	YES
43	MYL9	MYL9	MYL9	1337	0.23	0.54	YES
44	COL4A4	COL4A4	COL4A4	1391	0.22	0.54	YES
45	IBSP	IBSP	IBSP	1411	0.22	0.54	YES
46	COL6A1	COL6A1	COL6A1	1412	0.22	0.55	YES
47	VTN	VTN	VTN	1414	0.22	0.56	YES
48	LAMA4	LAMA4	LAMA4	1415	0.22	0.56	YES
49	COL6A2	COL6A2	COL6A2	1456	0.22	0.57	YES
50	LAMA1	LAMA1	LAMA1	1507	0.21	0.57	YES
51	ITGA5	ITGA5	ITGA5	1523	0.21	0.58	YES
52	LAMA3	LAMA3	LAMA3	1549	0.21	0.58	YES
53	ITGB6	ITGB6	ITGB6	1584	0.21	0.59	YES
54	ITGA4	ITGA4	ITGA4	1679	0.2	0.59	YES
55	PDGFB	PDGFB	PDGFB	1705	0.19	0.59	YES
56	SHC2	SHC2	SHC2	1722	0.19	0.6	YES
57	LAMC2	LAMC2	LAMC2	1725	0.19	0.6	YES
58	PRKCA	PRKCA	PRKCA	1761	0.19	0.6	YES
59	MYLK	MYLK	MYLK	1784	0.19	0.61	YES
60	CAV1	CAV1	CAV1	1791	0.19	0.61	YES
61	TLN2	TLN2	TLN2	1804	0.18	0.62	YES
62	KDR	KDR	KDR	1913	0.18	0.62	YES
63	HGF	HGF	HGF	1924	0.18	0.62	YES
64	FIGF	FIGF	FIGF	2007	0.17	0.62	YES
65	LAMC3	LAMC3	LAMC3	2023	0.17	0.63	YES
66	PIK3CG	PIK3CG	PIK3CG	2105	0.16	0.63	YES
67	SHC3	SHC3	SHC3	2142	0.16	0.63	YES
68	COL2A1	COL2A1	COL2A1	2157	0.16	0.63	YES
69	AKT3	AKT3	AKT3	2213	0.16	0.64	YES
70	PIK3R1	PIK3R1	PIK3R1	2283	0.15	0.64	YES
71	LAMB2	LAMB2	LAMB2	2380	0.14	0.64	YES
72	ACTN1	ACTN1	ACTN1	2421	0.14	0.64	YES
73	LAMB1	LAMB1	LAMB1	2443	0.14	0.64	YES
74	COL4A2	COL4A2	COL4A2	2459	0.14	0.64	YES
75	PIK3CD	PIK3CD	PIK3CD	2506	0.14	0.64	YES
76	COL4A1	COL4A1	COL4A1	2515	0.14	0.65	YES
77	ITGAV	ITGAV	ITGAV	2581	0.13	0.65	YES
78	THBS3	THBS3	THBS3	2610	0.13	0.65	YES
79	PARVA	PARVA	PARVA	2648	0.13	0.65	YES
80	ITGA3	ITGA3	ITGA3	2672	0.13	0.66	YES
81	PAK3	PAK3	PAK3	2767	0.12	0.65	YES
82	LAMB4	LAMB4	LAMB4	2771	0.12	0.66	YES
83	PARVB	PARVB	PARVB	2804	0.12	0.66	YES
84	ITGB1	ITGB1	ITGB1	2836	0.12	0.66	YES
85	PDGFD	PDGFD	PDGFD	2933	0.12	0.66	YES
86	COL6A6	COL6A6	COL6A6	2945	0.12	0.66	YES
87	LAMB3	LAMB3	LAMB3	2948	0.12	0.66	YES
88	TNR	TNR	TNR	2961	0.12	0.67	YES
89	ROCK2	ROCK2	ROCK2	3027	0.11	0.67	YES
90	ITGA6	ITGA6	ITGA6	3029	0.11	0.67	YES
91	RAPGEF1	RAPGEF1	RAPGEF1	3030	0.11	0.67	YES
92	FYN	FYN	FYN	3039	0.11	0.68	YES
93	ITGB5	ITGB5	ITGB5	3043	0.11	0.68	YES
94	MYL7	MYL7	MYL7	3048	0.11	0.68	YES
95	LAMC1	LAMC1	LAMC1	3058	0.11	0.68	YES
96	PDGFA	PDGFA	PDGFA	3072	0.11	0.69	YES
97	PXN	PXN	PXN	3089	0.11	0.69	YES
98	PIK3R5	PIK3R5	PIK3R5	3156	0.1	0.69	YES
99	MET	MET	MET	3208	0.1	0.69	YES
100	TLN1	TLN1	TLN1	3272	0.1	0.69	YES
101	PRKCB	PRKCB	PRKCB	3324	0.098	0.69	YES
102	VAV2	VAV2	VAV2	3329	0.098	0.69	YES
103	CAV2	CAV2	CAV2	3540	0.091	0.68	NO
104	PARVG	PARVG	PARVG	3584	0.09	0.68	NO
105	CCND1	CCND1	CCND1	3631	0.088	0.68	NO
106	VWF	VWF	VWF	3747	0.085	0.68	NO
107	FLNA	FLNA	FLNA	3768	0.084	0.68	NO
108	SPP1	SPP1	SPP1	3808	0.082	0.68	NO
109	VCL	VCL	VCL	3822	0.082	0.68	NO
110	DOCK1	DOCK1	DOCK1	3825	0.082	0.68	NO
111	SHC4	SHC4	SHC4	3854	0.081	0.69	NO
112	ILK	ILK	ILK	3889	0.08	0.69	NO
113	IGF1R	IGF1R	IGF1R	4006	0.075	0.68	NO
114	MAPK8	MAPK8	MAPK8	4036	0.075	0.68	NO
115	EGFR	EGFR	EGFR	4060	0.074	0.68	NO
116	BIRC2	BIRC2	BIRC2	4193	0.07	0.68	NO
117	FLT1	FLT1	FLT1	4248	0.068	0.68	NO
118	BCAR1	BCAR1	BCAR1	4296	0.067	0.68	NO
119	ZYX	ZYX	ZYX	4367	0.065	0.68	NO
120	ITGB4	ITGB4	ITGB4	4485	0.061	0.67	NO
121	ITGA2	ITGA2	ITGA2	4709	0.057	0.66	NO
122	SHC1	SHC1	SHC1	4745	0.056	0.66	NO
123	PTEN	PTEN	PTEN	5081	0.048	0.64	NO
124	SOS2	SOS2	SOS2	5145	0.047	0.64	NO
125	VAV3	VAV3	VAV3	5176	0.047	0.64	NO
126	MYL12A	MYL12A	MYL12A	5220	0.046	0.64	NO
127	PTK2	PTK2	PTK2	5277	0.045	0.64	NO
128	RAC2	RAC2	RAC2	5281	0.045	0.64	NO
129	CRK	CRK	CRK	5360	0.043	0.64	NO
130	RAP1A	RAP1A	RAP1A	5378	0.043	0.64	NO
131	ROCK1	ROCK1	ROCK1	5448	0.042	0.63	NO
132	PIP5K1C	PIP5K1C	PIP5K1C	5587	0.039	0.63	NO
133	SRC	SRC	SRC	5662	0.038	0.62	NO
134	VEGFB	VEGFB	VEGFB	5713	0.037	0.62	NO
135	JUN	JUN	JUN	5847	0.035	0.62	NO
136	CHAD	CHAD	CHAD	5876	0.035	0.62	NO
137	PPP1R12A	PPP1R12A	PPP1R12A	6070	0.032	0.6	NO
138	AKT1	AKT1	AKT1	6455	0.026	0.58	NO
139	PIK3CA	PIK3CA	PIK3CA	6594	0.025	0.58	NO
140	CTNNB1	CTNNB1	CTNNB1	6626	0.024	0.58	NO
141	GSK3B	GSK3B	GSK3B	6665	0.024	0.58	NO
142	ACTB	ACTB	ACTB	6686	0.024	0.57	NO
143	XIAP	XIAP	XIAP	6705	0.023	0.57	NO
144	ARHGAP5	ARHGAP5	ARHGAP5	6772	0.022	0.57	NO
145	CCND2	CCND2	CCND2	6821	0.022	0.57	NO
146	RAP1B	RAP1B	RAP1B	6997	0.02	0.56	NO
147	CCND3	CCND3	CCND3	7001	0.02	0.56	NO
148	MAPK1	MAPK1	MAPK1	7096	0.019	0.56	NO
149	DIAPH1	DIAPH1	DIAPH1	7177	0.018	0.55	NO
150	CAPN2	CAPN2	CAPN2	7201	0.017	0.55	NO
151	VASP	VASP	VASP	7211	0.017	0.55	NO
152	RHOA	RHOA	RHOA	7290	0.016	0.55	NO
153	PAK2	PAK2	PAK2	7510	0.014	0.54	NO
154	PDPK1	PDPK1	PDPK1	7614	0.013	0.53	NO
155	SOS1	SOS1	SOS1	7663	0.013	0.53	NO
156	CRKL	CRKL	CRKL	7686	0.012	0.53	NO
157	ELK1	ELK1	ELK1	7699	0.012	0.53	NO
158	CDC42	CDC42	CDC42	7701	0.012	0.53	NO
159	LAMA5	LAMA5	LAMA5	7895	0.01	0.52	NO
160	PPP1CA	PPP1CA	PPP1CA	7921	0.0099	0.52	NO
161	GRLF1	GRLF1	GRLF1	8099	0.0084	0.51	NO
162	AKT2	AKT2	AKT2	8176	0.0075	0.5	NO
163	FLNB	FLNB	FLNB	8185	0.0074	0.5	NO
164	MAP2K1	MAP2K1	MAP2K1	8211	0.0071	0.5	NO
165	ACTN4	ACTN4	ACTN4	8225	0.007	0.5	NO
166	VAV1	VAV1	VAV1	8577	0.0032	0.48	NO
167	MAPK9	MAPK9	MAPK9	9328	-0.0036	0.44	NO
168	GRB2	GRB2	GRB2	9523	-0.0055	0.43	NO
169	PPP1CB	PPP1CB	PPP1CB	9749	-0.0075	0.42	NO
170	MYL12B	MYL12B	MYL12B	9755	-0.0075	0.42	NO
171	ACTG1	ACTG1	ACTG1	9993	-0.0096	0.4	NO
172	PIK3R2	PIK3R2	PIK3R2	10327	-0.012	0.39	NO
173	RAF1	RAF1	RAF1	10715	-0.016	0.37	NO
174	BAD	BAD	BAD	10768	-0.017	0.36	NO
175	PPP1CC	PPP1CC	PPP1CC	10860	-0.018	0.36	NO
176	PAK1	PAK1	PAK1	11209	-0.021	0.34	NO
177	BCL2	BCL2	BCL2	11595	-0.025	0.32	NO
178	RAC1	RAC1	RAC1	11810	-0.027	0.31	NO
179	MAPK3	MAPK3	MAPK3	12238	-0.032	0.29	NO
180	COL11A2	COL11A2	COL11A2	12443	-0.034	0.28	NO
181	ITGB8	ITGB8	ITGB8	12634	-0.036	0.27	NO
182	PIK3CB	PIK3CB	PIK3CB	12946	-0.04	0.25	NO
183	PAK6	PAK6	PAK6	13455	-0.046	0.22	NO
184	PGF	PGF	PGF	13942	-0.053	0.2	NO
185	PAK4	PAK4	PAK4	14104	-0.055	0.19	NO
186	ITGB7	ITGB7	ITGB7	14110	-0.055	0.19	NO
187	BIRC3	BIRC3	BIRC3	14392	-0.06	0.18	NO
188	RAC3	RAC3	RAC3	14667	-0.066	0.17	NO
189	BRAF	BRAF	BRAF	14967	-0.072	0.15	NO
190	ERBB2	ERBB2	ERBB2	15187	-0.078	0.14	NO
191	PIK3R3	PIK3R3	PIK3R3	15707	-0.092	0.12	NO
192	VEGFA	VEGFA	VEGFA	16216	-0.11	0.092	NO
193	PAK7	PAK7	PAK7	16361	-0.12	0.088	NO
194	MYL5	MYL5	MYL5	17135	-0.16	0.05	NO
195	PRKCG	PRKCG	PRKCG	17294	-0.17	0.046	NO
196	MAPK10	MAPK10	MAPK10	17701	-0.2	0.029	NO
197	ITGA2B	ITGA2B	ITGA2B	17971	-0.24	0.022	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: BIOCARTA CARM ER PATHWAY.

Figure S12. 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 HDAC PATHWAY

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	ACTN2	ACTN2	ACTN2	21	1.5	0.21	YES
2	CTNNA3	CTNNA3	CTNNA3	147	0.87	0.32	YES
3	SORBS1	SORBS1	SORBS1	272	0.55	0.38	YES
4	ACTN3	ACTN3	ACTN3	433	0.42	0.43	YES
5	SNAI1	SNAI1	SNAI1	1059	0.26	0.43	YES
6	PTPRM	PTPRM	PTPRM	1226	0.24	0.46	YES
7	PTPRB	PTPRB	PTPRB	1641	0.2	0.46	YES
8	TGFBR2	TGFBR2	TGFBR2	1838	0.18	0.48	YES
9	ACTN1	ACTN1	ACTN1	2421	0.14	0.46	YES
10	WASF3	WASF3	WASF3	2454	0.14	0.48	YES
11	SNAI2	SNAI2	SNAI2	2510	0.14	0.5	YES
12	FGFR1	FGFR1	FGFR1	2699	0.13	0.5	YES
13	FYN	FYN	FYN	3039	0.11	0.5	YES
14	CTNNA2	CTNNA2	CTNNA2	3149	0.1	0.51	YES
15	MET	MET	MET	3208	0.1	0.52	YES
16	TCF7	TCF7	TCF7	3418	0.095	0.52	YES
17	TGFBR1	TGFBR1	TGFBR1	3516	0.092	0.52	YES
18	VCL	VCL	VCL	3822	0.082	0.52	YES
19	PVRL3	PVRL3	PVRL3	3831	0.082	0.53	YES
20	LEF1	LEF1	LEF1	3954	0.078	0.53	YES
21	IGF1R	IGF1R	IGF1R	4006	0.075	0.54	YES
22	EGFR	EGFR	EGFR	4060	0.074	0.55	YES
23	WAS	WAS	WAS	4432	0.063	0.54	YES
24	PTPRJ	PTPRJ	PTPRJ	4544	0.06	0.54	YES
25	TCF7L1	TCF7L1	TCF7L1	4626	0.058	0.54	YES
26	INSR	INSR	INSR	4738	0.056	0.54	YES
27	LMO7	LMO7	LMO7	4778	0.055	0.55	YES
28	TCF7L2	TCF7L2	TCF7L2	5002	0.05	0.54	NO
29	RAC2	RAC2	RAC2	5281	0.045	0.53	NO
30	SRC	SRC	SRC	5662	0.038	0.52	NO
31	IQGAP1	IQGAP1	IQGAP1	5792	0.036	0.52	NO
32	PTPN1	PTPN1	PTPN1	5846	0.035	0.52	NO
33	CSNK2A2	CSNK2A2	CSNK2A2	5861	0.035	0.52	NO
34	CTNNB1	CTNNB1	CTNNB1	6626	0.024	0.48	NO
35	ACTB	ACTB	ACTB	6686	0.024	0.48	NO
36	EP300	EP300	EP300	6825	0.022	0.48	NO
37	SMAD4	SMAD4	SMAD4	7043	0.02	0.47	NO
38	MAPK1	MAPK1	MAPK1	7096	0.019	0.47	NO
39	RHOA	RHOA	RHOA	7290	0.016	0.46	NO
40	CREBBP	CREBBP	CREBBP	7325	0.016	0.46	NO
41	MAP3K7	MAP3K7	MAP3K7	7673	0.012	0.44	NO
42	CDC42	CDC42	CDC42	7701	0.012	0.44	NO
43	ACTN4	ACTN4	ACTN4	8225	0.007	0.42	NO
44	FER	FER	FER	8694	0.0022	0.39	NO
45	CSNK2A1	CSNK2A1	CSNK2A1	9020	-0.0008	0.37	NO
46	PTPRF	PTPRF	PTPRF	9262	-0.003	0.36	NO
47	WASL	WASL	WASL	9564	-0.0059	0.34	NO
48	SSX2IP	SSX2IP	SSX2IP	9857	-0.0084	0.33	NO
49	PVRL2	PVRL2	PVRL2	9860	-0.0084	0.33	NO
50	CTNNA1	CTNNA1	CTNNA1	9907	-0.0088	0.33	NO
51	ACTG1	ACTG1	ACTG1	9993	-0.0096	0.33	NO
52	PTPN6	PTPN6	PTPN6	10178	-0.011	0.32	NO
53	YES1	YES1	YES1	10290	-0.012	0.31	NO
54	WASF2	WASF2	WASF2	10360	-0.013	0.31	NO
55	TJP1	TJP1	TJP1	10497	-0.014	0.31	NO
56	CSNK2B	CSNK2B	CSNK2B	11656	-0.026	0.25	NO
57	RAC1	RAC1	RAC1	11810	-0.027	0.24	NO
58	CTNND1	CTNND1	CTNND1	11973	-0.029	0.24	NO
59	MAPK3	MAPK3	MAPK3	12238	-0.032	0.23	NO
60	SMAD2	SMAD2	SMAD2	12476	-0.035	0.22	NO
61	FARP2	FARP2	FARP2	12539	-0.035	0.22	NO
62	MLLT4	MLLT4	MLLT4	12683	-0.037	0.22	NO
63	CDH1	CDH1	CDH1	13261	-0.044	0.19	NO
64	PVRL1	PVRL1	PVRL1	13298	-0.044	0.2	NO
65	WASF1	WASF1	WASF1	13345	-0.045	0.2	NO
66	ACP1	ACP1	ACP1	13391	-0.045	0.2	NO
67	SMAD3	SMAD3	SMAD3	13421	-0.046	0.21	NO
68	BAIAP2	BAIAP2	BAIAP2	13640	-0.049	0.2	NO
69	NLK	NLK	NLK	13667	-0.049	0.21	NO
70	PARD3	PARD3	PARD3	13808	-0.051	0.21	NO
71	RAC3	RAC3	RAC3	14667	-0.066	0.17	NO
72	ERBB2	ERBB2	ERBB2	15187	-0.078	0.15	NO
73	PVRL4	PVRL4	PVRL4	17430	-0.18	0.051	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: BIOCARTA HDAC PATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HDAC 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 EGF PATHWAY

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	CAMK2A	CAMK2A	CAMK2A	128	0.97	0.2	YES
2	CAMK2B	CAMK2B	CAMK2B	175	0.79	0.36	YES
3	MAPT	MAPT	MAPT	222	0.66	0.5	YES
4	AGT	AGT	AGT	234	0.63	0.63	YES
5	PRKCA	PRKCA	PRKCA	1761	0.19	0.58	NO
6	MYLK	MYLK	MYLK	1784	0.19	0.62	NO
7	STAT4	STAT4	STAT4	2865	0.12	0.59	NO
8	FYN	FYN	FYN	3039	0.11	0.6	NO
9	PRKCB	PRKCB	PRKCB	3324	0.098	0.61	NO
10	CAMK2D	CAMK2D	CAMK2D	3828	0.082	0.6	NO
11	MAPK8	MAPK8	MAPK8	4036	0.075	0.6	NO
12	STAT2	STAT2	STAT2	4234	0.069	0.61	NO
13	STAT1	STAT1	STAT1	4431	0.063	0.61	NO
14	STAT5B	STAT5B	STAT5B	4638	0.058	0.61	NO
15	SHC1	SHC1	SHC1	4745	0.056	0.62	NO
16	GNA11	GNA11	GNA11	5103	0.048	0.61	NO
17	KNG1	KNG1	KNG1	5273	0.045	0.61	NO
18	PLCG1	PLCG1	PLCG1	5399	0.042	0.61	NO
19	GNB1	GNB1	GNB1	5805	0.036	0.59	NO
20	CALM1	CALM1	CALM1	6049	0.032	0.59	NO
21	PTK2B	PTK2B	PTK2B	6162	0.031	0.59	NO
22	STAT5A	STAT5A	STAT5A	6715	0.023	0.56	NO
23	CAMK2G	CAMK2G	CAMK2G	6721	0.023	0.57	NO
24	JAK2	JAK2	JAK2	6768	0.023	0.57	NO
25	MAPK1	MAPK1	MAPK1	7096	0.019	0.56	NO
26	GNAI1	GNAI1	GNAI1	7163	0.018	0.56	NO
27	SOS1	SOS1	SOS1	7663	0.013	0.53	NO
28	MAP2K1	MAP2K1	MAP2K1	8211	0.0071	0.5	NO
29	CALM3	CALM3	CALM3	8268	0.0065	0.5	NO
30	MAPK14	MAPK14	MAPK14	8829	0.001	0.47	NO
31	CALM2	CALM2	CALM2	8837	0.00092	0.47	NO
32	GRB2	GRB2	GRB2	9523	-0.0055	0.43	NO
33	STAT6	STAT6	STAT6	9788	-0.0078	0.42	NO
34	RAF1	RAF1	RAF1	10715	-0.016	0.37	NO
35	CDK5	CDK5	CDK5	10935	-0.018	0.37	NO
36	STAT3	STAT3	STAT3	11471	-0.024	0.34	NO
37	MAPK3	MAPK3	MAPK3	12238	-0.032	0.31	NO
38	MAP2K2	MAP2K2	MAP2K2	12299	-0.033	0.31	NO
39	F2	F2	F2	12461	-0.034	0.31	NO
40	GNGT1	GNGT1	GNGT1	14607	-0.064	0.2	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: BIOCARTA EGF PATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA EGF 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 ERK PATHWAY

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	PPP1R3A	PPP1R3A	PPP1R3A	43	1.4	0.095	YES
2	PRKAG3	PRKAG3	PRKAG3	48	1.4	0.19	YES
3	PHKG1	PHKG1	PHKG1	141	0.92	0.25	YES
4	PYGM	PYGM	PYGM	143	0.9	0.31	YES
5	SORBS1	SORBS1	SORBS1	272	0.55	0.34	YES
6	PRKAA2	PRKAA2	PRKAA2	359	0.46	0.37	YES
7	FBP2	FBP2	FBP2	367	0.45	0.4	YES
8	PPARGC1A	PPARGC1A	PPARGC1A	458	0.41	0.42	YES
9	PPP1R3C	PPP1R3C	PPP1R3C	546	0.38	0.44	YES
10	SLC2A4	SLC2A4	SLC2A4	613	0.35	0.46	YES
11	PDE3A	PDE3A	PDE3A	732	0.32	0.48	YES
12	ACACB	ACACB	ACACB	1176	0.25	0.47	YES
13	IRS1	IRS1	IRS1	1471	0.22	0.47	YES
14	SHC2	SHC2	SHC2	1722	0.19	0.46	YES
15	HK3	HK3	HK3	1898	0.18	0.47	YES
16	PIK3CG	PIK3CG	PIK3CG	2105	0.16	0.47	YES
17	SHC3	SHC3	SHC3	2142	0.16	0.48	YES
18	AKT3	AKT3	AKT3	2213	0.16	0.48	YES
19	PIK3R1	PIK3R1	PIK3R1	2283	0.15	0.49	YES
20	PRKAB2	PRKAB2	PRKAB2	2376	0.14	0.49	YES
21	PIK3CD	PIK3CD	PIK3CD	2506	0.14	0.5	YES
22	CBLB	CBLB	CBLB	2878	0.12	0.48	YES
23	FOXO1	FOXO1	FOXO1	2882	0.12	0.49	YES
24	IRS2	IRS2	IRS2	3005	0.11	0.49	YES
25	RHOQ	RHOQ	RHOQ	3028	0.11	0.5	YES
26	RAPGEF1	RAPGEF1	RAPGEF1	3030	0.11	0.51	YES
27	PIK3R5	PIK3R5	PIK3R5	3156	0.1	0.51	YES
28	PRKACB	PRKACB	PRKACB	3285	0.1	0.51	NO
29	SHC4	SHC4	SHC4	3854	0.081	0.48	NO
30	PRKAR2A	PRKAR2A	PRKAR2A	3922	0.079	0.48	NO
31	MAPK8	MAPK8	MAPK8	4036	0.075	0.48	NO
32	PYGL	PYGL	PYGL	4126	0.072	0.48	NO
33	SH2B2	SH2B2	SH2B2	4146	0.071	0.49	NO
34	PRKAR2B	PRKAR2B	PRKAR2B	4318	0.066	0.48	NO
35	INSR	INSR	INSR	4738	0.056	0.46	NO
36	SHC1	SHC1	SHC1	4745	0.056	0.46	NO
37	CBL	CBL	CBL	5031	0.05	0.45	NO
38	CALML6	CALML6	CALML6	5048	0.049	0.46	NO
39	SOS2	SOS2	SOS2	5145	0.047	0.45	NO
40	PCK1	PCK1	PCK1	5301	0.044	0.45	NO
41	CRK	CRK	CRK	5360	0.043	0.45	NO
42	PHKA1	PHKA1	PHKA1	5462	0.042	0.44	NO
43	SOCS4	SOCS4	SOCS4	5509	0.041	0.44	NO
44	PRKACA	PRKACA	PRKACA	5610	0.039	0.44	NO
45	INPP5K	INPP5K	INPP5K	5659	0.038	0.44	NO
46	SOCS3	SOCS3	SOCS3	5665	0.038	0.44	NO
47	PRKAA1	PRKAA1	PRKAA1	5674	0.038	0.45	NO
48	MTOR	MTOR	MTOR	5786	0.036	0.44	NO
49	GYS1	GYS1	GYS1	5804	0.036	0.44	NO
50	PTPN1	PTPN1	PTPN1	5846	0.035	0.44	NO
51	FLOT1	FLOT1	FLOT1	5922	0.034	0.44	NO
52	PRKAR1A	PRKAR1A	PRKAR1A	5926	0.034	0.44	NO
53	CALM1	CALM1	CALM1	6049	0.032	0.44	NO
54	PYGB	PYGB	PYGB	6086	0.032	0.44	NO
55	SOCS2	SOCS2	SOCS2	6131	0.031	0.44	NO
56	ARAF	ARAF	ARAF	6169	0.031	0.44	NO
57	RPTOR	RPTOR	RPTOR	6406	0.027	0.43	NO
58	AKT1	AKT1	AKT1	6455	0.026	0.43	NO
59	PIK3CA	PIK3CA	PIK3CA	6594	0.025	0.42	NO
60	GSK3B	GSK3B	GSK3B	6665	0.024	0.42	NO
61	NRAS	NRAS	NRAS	6901	0.021	0.41	NO
62	PHKB	PHKB	PHKB	6948	0.02	0.41	NO
63	MAPK1	MAPK1	MAPK1	7096	0.019	0.4	NO
64	FBP1	FBP1	FBP1	7102	0.019	0.4	NO
65	PPP1R3B	PPP1R3B	PPP1R3B	7139	0.018	0.4	NO
66	PDPK1	PDPK1	PDPK1	7614	0.013	0.38	NO
67	SOS1	SOS1	SOS1	7663	0.013	0.37	NO
68	CRKL	CRKL	CRKL	7686	0.012	0.37	NO
69	ELK1	ELK1	ELK1	7699	0.012	0.37	NO
70	PRKAG1	PRKAG1	PRKAG1	7722	0.012	0.37	NO
71	PPP1CA	PPP1CA	PPP1CA	7921	0.0099	0.36	NO
72	HK1	HK1	HK1	7970	0.0095	0.36	NO
73	EIF4E2	EIF4E2	EIF4E2	8038	0.0089	0.36	NO
74	AKT2	AKT2	AKT2	8176	0.0075	0.35	NO
75	EXOC7	EXOC7	EXOC7	8190	0.0074	0.35	NO
76	MAP2K1	MAP2K1	MAP2K1	8211	0.0071	0.35	NO
77	CALM3	CALM3	CALM3	8268	0.0065	0.35	NO
78	TSC1	TSC1	TSC1	8489	0.0041	0.34	NO
79	CALM2	CALM2	CALM2	8837	0.00092	0.32	NO
80	MKNK1	MKNK1	MKNK1	9066	-0.0013	0.3	NO
81	PTPRF	PTPRF	PTPRF	9262	-0.003	0.29	NO
82	MAPK9	MAPK9	MAPK9	9328	-0.0036	0.29	NO
83	GRB2	GRB2	GRB2	9523	-0.0055	0.28	NO
84	PKLR	PKLR	PKLR	9595	-0.0062	0.28	NO
85	PPP1CB	PPP1CB	PPP1CB	9749	-0.0075	0.27	NO
86	RHEB	RHEB	RHEB	9938	-0.0091	0.26	NO
87	TSC2	TSC2	TSC2	10157	-0.011	0.25	NO
88	PIK3R2	PIK3R2	PIK3R2	10327	-0.012	0.24	NO
89	RPS6KB2	RPS6KB2	RPS6KB2	10579	-0.015	0.23	NO
90	RAF1	RAF1	RAF1	10715	-0.016	0.22	NO
91	BAD	BAD	BAD	10768	-0.017	0.22	NO
92	PPP1CC	PPP1CC	PPP1CC	10860	-0.018	0.22	NO
93	INPP5D	INPP5D	INPP5D	11478	-0.024	0.18	NO
94	PRKAG2	PRKAG2	PRKAG2	11496	-0.024	0.18	NO
95	KRAS	KRAS	KRAS	11542	-0.024	0.18	NO
96	PRKCI	PRKCI	PRKCI	11546	-0.024	0.18	NO
97	PRKAB1	PRKAB1	PRKAB1	11617	-0.025	0.18	NO
98	RPS6KB1	RPS6KB1	RPS6KB1	11685	-0.026	0.18	NO
99	IKBKB	IKBKB	IKBKB	11926	-0.028	0.17	NO
100	TRIP10	TRIP10	TRIP10	12161	-0.031	0.16	NO
101	MAPK3	MAPK3	MAPK3	12238	-0.032	0.16	NO
102	MAP2K2	MAP2K2	MAP2K2	12299	-0.033	0.16	NO
103	GYS2	GYS2	GYS2	12456	-0.034	0.15	NO
104	EIF4E	EIF4E	EIF4E	12656	-0.037	0.14	NO
105	PRKAR1B	PRKAR1B	PRKAR1B	12892	-0.039	0.13	NO
106	ACACA	ACACA	ACACA	12918	-0.04	0.13	NO
107	PIK3CB	PIK3CB	PIK3CB	12946	-0.04	0.13	NO
108	FLOT2	FLOT2	FLOT2	13052	-0.041	0.13	NO
109	PHKA2	PHKA2	PHKA2	13081	-0.041	0.13	NO
110	RPS6	RPS6	RPS6	13209	-0.043	0.13	NO
111	CALML3	CALML3	CALML3	13378	-0.045	0.12	NO
112	PRKCZ	PRKCZ	PRKCZ	13381	-0.045	0.12	NO
113	FASN	FASN	FASN	13630	-0.049	0.11	NO
114	PCK2	PCK2	PCK2	14018	-0.054	0.096	NO
115	SOCS1	SOCS1	SOCS1	14625	-0.064	0.067	NO
116	HK2	HK2	HK2	14758	-0.067	0.064	NO
117	PHKG2	PHKG2	PHKG2	14764	-0.068	0.069	NO
118	BRAF	BRAF	BRAF	14967	-0.072	0.062	NO
119	EIF4EBP1	EIF4EBP1	EIF4EBP1	15178	-0.078	0.056	NO
120	PIK3R3	PIK3R3	PIK3R3	15707	-0.092	0.034	NO
121	MKNK2	MKNK2	MKNK2	15823	-0.097	0.034	NO
122	PPP1R3D	PPP1R3D	PPP1R3D	15831	-0.097	0.04	NO
123	SREBF1	SREBF1	SREBF1	15899	-0.099	0.043	NO
124	PDE3B	PDE3B	PDE3B	15902	-0.099	0.05	NO
125	LIPE	LIPE	LIPE	16653	-0.13	0.017	NO
126	CBLC	CBLC	CBLC	17186	-0.16	-0.00089	NO
127	GCK	GCK	GCK	17235	-0.16	0.0076	NO
128	PRKX	PRKX	PRKX	17497	-0.18	0.0057	NO
129	CALML5	CALML5	CALML5	17675	-0.2	0.0094	NO
130	MAPK10	MAPK10	MAPK10	17701	-0.2	0.022	NO
131	IRS4	IRS4	IRS4	17834	-0.21	0.029	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: BIOCARTA ERK PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ERK 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 FMLP 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	MYH1	MYH1	MYH1	16	1.6	0.056	YES
2	MYLPF	MYLPF	MYLPF	20	1.6	0.11	YES
3	ACTN2	ACTN2	ACTN2	21	1.5	0.17	YES
4	MYH8	MYH8	MYH8	25	1.5	0.22	YES
5	MYL2	MYL2	MYL2	27	1.5	0.28	YES
6	MYH7	MYH7	MYH7	53	1.4	0.33	YES
7	MYH2	MYH2	MYH2	68	1.3	0.37	YES
8	MYH4	MYH4	MYH4	72	1.2	0.42	YES
9	MYH6	MYH6	MYH6	82	1.2	0.46	YES
10	MYH3	MYH3	MYH3	83	1.2	0.5	YES
11	CTNNA3	CTNNA3	CTNNA3	147	0.87	0.53	YES
12	MYH13	MYH13	MYH13	166	0.82	0.56	YES
13	JAM2	JAM2	JAM2	368	0.45	0.57	YES
14	MRAS	MRAS	MRAS	387	0.44	0.58	YES
15	ACTN3	ACTN3	ACTN3	433	0.42	0.6	YES
16	PRKCQ	PRKCQ	PRKCQ	582	0.37	0.6	YES
17	MYH7B	MYH7B	MYH7B	624	0.35	0.61	YES
18	MYH15	MYH15	MYH15	936	0.28	0.6	YES
19	MPDZ	MPDZ	MPDZ	1050	0.27	0.61	YES
20	JAM3	JAM3	JAM3	1085	0.26	0.62	YES
21	MYL9	MYL9	MYL9	1337	0.23	0.61	YES
22	MYH11	MYH11	MYH11	1344	0.23	0.62	YES
23	CLDN5	CLDN5	CLDN5	1368	0.23	0.62	YES
24	PRKCA	PRKCA	PRKCA	1761	0.19	0.61	NO
25	ZAK	ZAK	ZAK	1978	0.17	0.6	NO
26	CLDN14	CLDN14	CLDN14	2062	0.17	0.61	NO
27	CLDN11	CLDN11	CLDN11	2074	0.16	0.61	NO
28	AKT3	AKT3	AKT3	2213	0.16	0.61	NO
29	ACTN1	ACTN1	ACTN1	2421	0.14	0.6	NO
30	MYH10	MYH10	MYH10	2611	0.13	0.6	NO
31	MYL7	MYL7	MYL7	3048	0.11	0.58	NO
32	CTNNA2	CTNNA2	CTNNA2	3149	0.1	0.58	NO
33	CLDN9	CLDN9	CLDN9	3233	0.1	0.57	NO
34	PRKCB	PRKCB	PRKCB	3324	0.098	0.57	NO
35	RRAS	RRAS	RRAS	3435	0.095	0.57	NO
36	PPP2R2C	PPP2R2C	PPP2R2C	3748	0.085	0.56	NO
37	CLDN19	CLDN19	CLDN19	3873	0.08	0.55	NO
38	AMOTL1	AMOTL1	AMOTL1	4350	0.066	0.53	NO
39	EPB41L3	EPB41L3	EPB41L3	4471	0.062	0.52	NO
40	GNAI2	GNAI2	GNAI2	4539	0.06	0.52	NO
41	MYH9	MYH9	MYH9	4601	0.059	0.52	NO
42	EPB41L2	EPB41L2	EPB41L2	4742	0.056	0.52	NO
43	TJAP1	TJAP1	TJAP1	4792	0.055	0.52	NO
44	HCLS1	HCLS1	HCLS1	5005	0.05	0.51	NO
45	PTEN	PTEN	PTEN	5081	0.048	0.5	NO
46	MYL12A	MYL12A	MYL12A	5220	0.046	0.5	NO
47	SRC	SRC	SRC	5662	0.038	0.48	NO
48	CSDA	CSDA	CSDA	5811	0.036	0.47	NO
49	CSNK2A2	CSNK2A2	CSNK2A2	5861	0.035	0.47	NO
50	LLGL1	LLGL1	LLGL1	5899	0.035	0.47	NO
51	CTTN	CTTN	CTTN	6435	0.027	0.44	NO
52	AKT1	AKT1	AKT1	6455	0.026	0.44	NO
53	RRAS2	RRAS2	RRAS2	6512	0.026	0.44	NO
54	CTNNB1	CTNNB1	CTNNB1	6626	0.024	0.43	NO
55	ACTB	ACTB	ACTB	6686	0.024	0.43	NO
56	SPTAN1	SPTAN1	SPTAN1	6811	0.022	0.42	NO
57	NRAS	NRAS	NRAS	6901	0.021	0.42	NO
58	RAB3B	RAB3B	RAB3B	7058	0.019	0.41	NO
59	GNAI1	GNAI1	GNAI1	7163	0.018	0.4	NO
60	RHOA	RHOA	RHOA	7290	0.016	0.4	NO
61	CLDN23	CLDN23	CLDN23	7569	0.014	0.38	NO
62	CDC42	CDC42	CDC42	7701	0.012	0.38	NO
63	MAGI2	MAGI2	MAGI2	7881	0.01	0.37	NO
64	PPP2R1A	PPP2R1A	PPP2R1A	7944	0.0098	0.36	NO
65	AKT2	AKT2	AKT2	8176	0.0075	0.35	NO
66	ACTN4	ACTN4	ACTN4	8225	0.007	0.35	NO
67	ASH1L	ASH1L	ASH1L	8289	0.0063	0.35	NO
68	EXOC4	EXOC4	EXOC4	8415	0.005	0.34	NO
69	RAB13	RAB13	RAB13	8775	0.0015	0.32	NO
70	PPP2R2D	PPP2R2D	PPP2R2D	8915	0.0002	0.31	NO
71	CSNK2A1	CSNK2A1	CSNK2A1	9020	-0.0008	0.31	NO
72	MPP5	MPP5	MPP5	9086	-0.0014	0.3	NO
73	GNAI3	GNAI3	GNAI3	9176	-0.0022	0.3	NO
74	EXOC3	EXOC3	EXOC3	9512	-0.0054	0.28	NO
75	MYL12B	MYL12B	MYL12B	9755	-0.0075	0.27	NO
76	CASK	CASK	CASK	9906	-0.0088	0.26	NO
77	CTNNA1	CTNNA1	CTNNA1	9907	-0.0088	0.26	NO
78	ACTG1	ACTG1	ACTG1	9993	-0.0096	0.26	NO
79	PPP2R1B	PPP2R1B	PPP2R1B	10012	-0.0097	0.26	NO
80	VAPA	VAPA	VAPA	10027	-0.0098	0.26	NO
81	YES1	YES1	YES1	10290	-0.012	0.24	NO
82	SYMPK	SYMPK	SYMPK	10326	-0.012	0.24	NO
83	TJP1	TJP1	TJP1	10497	-0.014	0.23	NO
84	PPP2CB	PPP2CB	PPP2CB	10943	-0.018	0.21	NO
85	PPP2CA	PPP2CA	PPP2CA	11335	-0.022	0.19	NO
86	KRAS	KRAS	KRAS	11542	-0.024	0.18	NO
87	PRKCI	PRKCI	PRKCI	11546	-0.024	0.18	NO
88	CSNK2B	CSNK2B	CSNK2B	11656	-0.026	0.17	NO
89	CDK4	CDK4	CDK4	11701	-0.026	0.17	NO
90	MAGI1	MAGI1	MAGI1	12027	-0.03	0.15	NO
91	INADL	INADL	INADL	12082	-0.03	0.15	NO
92	PARD6G	PARD6G	PARD6G	12637	-0.036	0.12	NO
93	PRKCH	PRKCH	PRKCH	12672	-0.037	0.12	NO
94	MLLT4	MLLT4	MLLT4	12683	-0.037	0.12	NO
95	F11R	F11R	F11R	13022	-0.041	0.11	NO
96	PRKCD	PRKCD	PRKCD	13341	-0.045	0.09	NO
97	PRKCZ	PRKCZ	PRKCZ	13381	-0.045	0.089	NO
98	PRKCE	PRKCE	PRKCE	13654	-0.049	0.076	NO
99	PARD3	PARD3	PARD3	13808	-0.051	0.07	NO
100	PPP2R2A	PPP2R2A	PPP2R2A	14403	-0.06	0.039	NO
101	PPP2R2B	PPP2R2B	PPP2R2B	14557	-0.063	0.033	NO
102	TJP2	TJP2	TJP2	14615	-0.064	0.032	NO
103	CLDN15	CLDN15	CLDN15	14724	-0.067	0.029	NO
104	CLDN2	CLDN2	CLDN2	14750	-0.067	0.03	NO
105	EPB41	EPB41	EPB41	14818	-0.068	0.029	NO
106	EPB41L1	EPB41L1	EPB41L1	15017	-0.073	0.021	NO
107	CLDN17	CLDN17	CLDN17	15175	-0.078	0.015	NO
108	MAGI3	MAGI3	MAGI3	15179	-0.078	0.017	NO
109	CLDN6	CLDN6	CLDN6	15409	-0.084	0.0079	NO
110	CLDN1	CLDN1	CLDN1	15476	-0.086	0.0074	NO
111	CLDN18	CLDN18	CLDN18	15737	-0.094	-0.0034	NO
112	CLDN20	CLDN20	CLDN20	16347	-0.12	-0.033	NO
113	MYH14	MYH14	MYH14	16416	-0.12	-0.032	NO
114	IGSF5	IGSF5	IGSF5	16939	-0.15	-0.055	NO
115	CLDN8	CLDN8	CLDN8	17124	-0.16	-0.06	NO
116	MYL5	MYL5	MYL5	17135	-0.16	-0.054	NO
117	PRKCG	PRKCG	PRKCG	17294	-0.17	-0.057	NO
118	PARD6A	PARD6A	PARD6A	17312	-0.17	-0.052	NO
119	LLGL2	LLGL2	LLGL2	17447	-0.18	-0.053	NO
120	CLDN16	CLDN16	CLDN16	17502	-0.18	-0.049	NO
121	PARD6B	PARD6B	PARD6B	17874	-0.22	-0.061	NO
122	CLDN10	CLDN10	CLDN10	18041	-0.24	-0.062	NO
123	CRB3	CRB3	CRB3	18067	-0.25	-0.054	NO
124	CLDN4	CLDN4	CLDN4	18101	-0.26	-0.046	NO
125	CLDN7	CLDN7	CLDN7	18178	-0.28	-0.04	NO
126	OCLN	OCLN	OCLN	18285	-0.32	-0.035	NO
127	CGN	CGN	CGN	18301	-0.32	-0.024	NO
128	CLDN3	CLDN3	CLDN3	18309	-0.33	-0.012	NO
129	TJP3	TJP3	TJP3	18359	-0.41	0.00011	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: BIOCARTA FMLP PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FMLP 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
BIOCARTA CHREBP2 PATHWAY	40	genes.ES.table	0.32	1.3	0.18	0.84	0.99	0.12	0.12	0.11	0.73	0.3
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.4	1.5	0.088	1	0.92	0.16	0.15	0.14	1	0.69
KEGG FATTY ACID METABOLISM	40	genes.ES.table	0.42	1.3	0.18	0.81	0.99	0.38	0.31	0.26	0.72	0.29
KEGG GLYCINE SERINE AND THREONINE METABOLISM	29	genes.ES.table	0.59	1.5	0.038	1	0.93	0.55	0.25	0.42	1	0.62
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.41	1.4	0.11	1	0.95	0.56	0.41	0.33	1	0.51
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.32	1.3	0.16	0.88	0.98	0.46	0.38	0.29	0.75	0.34
KEGG SELENOAMINO ACID METABOLISM	25	genes.ES.table	0.43	1.3	0.15	0.87	0.99	0.28	0.24	0.21	0.76	0.33
KEGG STARCH AND SUCROSE METABOLISM	39	genes.ES.table	0.57	1.5	0.061	1	0.92	0.41	0.16	0.34	1	0.78
KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES	25	genes.ES.table	0.52	1.4	0.093	0.92	0.97	0.28	0.13	0.24	0.78	0.36
KEGG BUTANOATE METABOLISM	29	genes.ES.table	0.46	1.3	0.11	0.83	0.98	0.45	0.33	0.3	0.7	0.3

genes ES table in pathway: BIOCARTA CHREBP2 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	UGT1A9	UGT1A9	UGT1A9	272	0.48	0.079	YES
2	UGT1A6	UGT1A6	UGT1A6	273	0.48	0.17	YES
3	UGT2A1	UGT2A1	UGT2A1	375	0.45	0.26	YES
4	CP	CP	CP	408	0.45	0.34	YES
5	UGT1A8	UGT1A8	UGT1A8	623	0.4	0.41	YES
6	UGT1A3	UGT1A3	UGT1A3	659	0.39	0.48	YES
7	UGT1A7	UGT1A7	UGT1A7	1113	0.33	0.53	YES
8	UGT1A4	UGT1A4	UGT1A4	1434	0.3	0.57	YES
9	UGT1A10	UGT1A10	UGT1A10	2604	0.22	0.55	YES
10	UGT1A1	UGT1A1	UGT1A1	2934	0.2	0.57	YES
11	UGT2B15	UGT2B15	UGT2B15	2960	0.2	0.6	YES
12	PPOX	PPOX	PPOX	4022	0.15	0.57	NO
13	UGT2B7	UGT2B7	UGT2B7	4986	0.12	0.55	NO
14	FECH	FECH	FECH	5219	0.11	0.56	NO
15	MMAB	MMAB	MMAB	5808	0.097	0.54	NO
16	GUSB	GUSB	GUSB	5912	0.094	0.55	NO
17	CPOX	CPOX	CPOX	6173	0.088	0.56	NO
18	EARS2	EARS2	EARS2	8354	0.046	0.45	NO
19	BLVRB	BLVRB	BLVRB	9010	0.036	0.42	NO
20	EPRS	EPRS	EPRS	9338	0.032	0.41	NO
21	COX15	COX15	COX15	9733	0.026	0.39	NO
22	FTH1	FTH1	FTH1	9796	0.025	0.39	NO
23	UROS	UROS	UROS	10198	0.02	0.38	NO
24	ALAD	ALAD	ALAD	10526	0.016	0.36	NO
25	COX10	COX10	COX10	10711	0.012	0.35	NO
26	BLVRA	BLVRA	BLVRA	12128	-0.0068	0.28	NO
27	ALAS1	ALAS1	ALAS1	12322	-0.0095	0.27	NO
28	ALAS2	ALAS2	ALAS2	13489	-0.029	0.21	NO
29	HMBS	HMBS	HMBS	13524	-0.03	0.21	NO
30	UROD	UROD	UROD	13680	-0.032	0.21	NO
31	HMOX1	HMOX1	HMOX1	15350	-0.072	0.14	NO
32	HMOX2	HMOX2	HMOX2	16857	-0.15	0.082	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 CHREBP2 PATHWAY.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 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 WNT 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	UGT1A9	UGT1A9	UGT1A9	272	0.48	0.049	YES
2	UGT1A6	UGT1A6	UGT1A6	273	0.48	0.11	YES
3	UGT2A1	UGT2A1	UGT2A1	375	0.45	0.17	YES
4	GCK	GCK	GCK	452	0.44	0.22	YES
5	UGT1A8	UGT1A8	UGT1A8	623	0.4	0.26	YES
6	UGT1A3	UGT1A3	UGT1A3	659	0.39	0.32	YES
7	AMY2B	AMY2B	AMY2B	757	0.38	0.36	YES
8	UGT1A7	UGT1A7	UGT1A7	1113	0.33	0.39	YES
9	AMY2A	AMY2A	AMY2A	1175	0.32	0.42	YES
10	UGT1A4	UGT1A4	UGT1A4	1434	0.3	0.45	YES
11	AMY1A	AMY1A	AMY1A	1456	0.3	0.49	YES
12	ENPP3	ENPP3	ENPP3	1486	0.29	0.53	YES
13	GBA3	GBA3	GBA3	1573	0.29	0.56	YES
14	UGT1A10	UGT1A10	UGT1A10	2604	0.22	0.53	YES
15	UGT1A1	UGT1A1	UGT1A1	2934	0.2	0.54	YES
16	UGT2B15	UGT2B15	UGT2B15	2960	0.2	0.56	YES
17	TREH	TREH	TREH	4189	0.14	0.52	NO
18	ENPP1	ENPP1	ENPP1	4811	0.12	0.5	NO
19	UGT2B7	UGT2B7	UGT2B7	4986	0.12	0.51	NO
20	UGDH	UGDH	UGDH	5298	0.11	0.5	NO
21	GUSB	GUSB	GUSB	5912	0.094	0.48	NO
22	GAA	GAA	GAA	6333	0.084	0.47	NO
23	AGL	AGL	AGL	7136	0.068	0.44	NO
24	GPI	GPI	GPI	7781	0.055	0.41	NO
25	PGM2L1	PGM2L1	PGM2L1	7858	0.054	0.41	NO
26	HK1	HK1	HK1	12363	-0.01	0.17	NO
27	HK3	HK3	HK3	12618	-0.014	0.16	NO
28	GYS2	GYS2	GYS2	12834	-0.017	0.15	NO
29	GBE1	GBE1	GBE1	13337	-0.026	0.12	NO
30	UGP2	UGP2	UGP2	13712	-0.033	0.11	NO
31	PGM1	PGM1	PGM1	14113	-0.041	0.09	NO
32	PYGB	PYGB	PYGB	14237	-0.044	0.089	NO
33	PGM2	PGM2	PGM2	14629	-0.052	0.075	NO
34	HK2	HK2	HK2	15422	-0.074	0.041	NO
35	GYS1	GYS1	GYS1	15719	-0.085	0.036	NO
36	MGAM	MGAM	MGAM	15915	-0.092	0.038	NO
37	GANC	GANC	GANC	16607	-0.13	0.018	NO
38	PYGL	PYGL	PYGL	17774	-0.29	-0.0072	NO
39	PYGM	PYGM	PYGM	17782	-0.29	0.032	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 WNT PATHWAY.

Figure S24. 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: KEGG FATTY ACID 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	WNT1	WNT1	WNT1	811	0.37	0.13	YES
2	WIF1	WIF1	WIF1	1169	0.32	0.26	YES
3	LEF1	LEF1	LEF1	1810	0.27	0.35	YES
4	FRAT1	FRAT1	FRAT1	2763	0.21	0.4	YES
5	SMAD4	SMAD4	SMAD4	5530	0.1	0.3	NO
6	NLK	NLK	NLK	5827	0.096	0.32	NO
7	APC	APC	APC	7490	0.061	0.26	NO
8	TAB1	TAB1	TAB1	7535	0.06	0.29	NO
9	FZD1	FZD1	FZD1	7710	0.057	0.3	NO
10	CREBBP	CREBBP	CREBBP	8581	0.043	0.28	NO
11	CTNNB1	CTNNB1	CTNNB1	10078	0.022	0.21	NO
12	HDAC1	HDAC1	HDAC1	10180	0.02	0.21	NO
13	GSK3B	GSK3B	GSK3B	10297	0.018	0.21	NO
14	TLE1	TLE1	TLE1	11447	0.0029	0.15	NO
15	CSNK2A1	CSNK2A1	CSNK2A1	12247	-0.0083	0.11	NO
16	CTBP1	CTBP1	CTBP1	12281	-0.0088	0.11	NO
17	AXIN1	AXIN1	AXIN1	12288	-0.0089	0.12	NO
18	MAP3K7	MAP3K7	MAP3K7	12293	-0.009	0.12	NO
19	CSNK1D	CSNK1D	CSNK1D	12300	-0.0092	0.12	NO
20	PPP2CA	PPP2CA	PPP2CA	13973	-0.038	0.052	NO
21	CCND1	CCND1	CCND1	14631	-0.052	0.041	NO
22	MYC	MYC	MYC	14874	-0.058	0.055	NO
23	BTRC	BTRC	BTRC	15352	-0.072	0.063	NO
24	CSNK1A1	CSNK1A1	CSNK1A1	15869	-0.091	0.077	NO
25	DVL1	DVL1	DVL1	16534	-0.13	0.1	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 FATTY ACID METABOLISM.

Figure S26. 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 GLYCINE SERINE AND THREONINE METABOLISM

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	CHDH	CHDH	CHDH	24	0.67	0.12	YES
2	CBS	CBS	CBS	50	0.61	0.22	YES
3	GNMT	GNMT	GNMT	412	0.44	0.28	YES
4	GATM	GATM	GATM	589	0.41	0.34	YES
5	PHGDH	PHGDH	PHGDH	705	0.39	0.4	YES
6	BHMT	BHMT	BHMT	1098	0.33	0.44	YES
7	PIPOX	PIPOX	PIPOX	1219	0.32	0.49	YES
8	MAOB	MAOB	MAOB	1534	0.29	0.52	YES
9	PSAT1	PSAT1	PSAT1	2911	0.2	0.48	YES
10	MAOA	MAOA	MAOA	3014	0.19	0.51	YES
11	GAMT	GAMT	GAMT	3304	0.18	0.52	YES
12	DMGDH	DMGDH	DMGDH	3534	0.17	0.54	YES
13	GCAT	GCAT	GCAT	4104	0.15	0.54	YES
14	SARDH	SARDH	SARDH	4111	0.15	0.56	YES
15	AOC2	AOC2	AOC2	4327	0.14	0.57	YES
16	PSPH	PSPH	PSPH	4518	0.13	0.59	YES
17	DAO	DAO	DAO	5272	0.11	0.57	NO
18	SHMT2	SHMT2	SHMT2	6301	0.085	0.52	NO
19	SHMT1	SHMT1	SHMT1	6317	0.084	0.54	NO
20	AGXT	AGXT	AGXT	6789	0.074	0.53	NO
21	SDS	SDS	SDS	8397	0.045	0.45	NO
22	DLD	DLD	DLD	8562	0.043	0.44	NO
23	CTH	CTH	CTH	8604	0.042	0.45	NO
24	ALAS1	ALAS1	ALAS1	12322	-0.0095	0.25	NO
25	SRR	SRR	SRR	12940	-0.019	0.22	NO
26	ALAS2	ALAS2	ALAS2	13489	-0.029	0.19	NO
27	GLYCTK	GLYCTK	GLYCTK	13525	-0.03	0.2	NO
28	AOC3	AOC3	AOC3	16991	-0.16	0.037	NO
29	GLDC	GLDC	GLDC	17383	-0.22	0.053	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 GLYCINE SERINE AND THREONINE METABOLISM.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCINE SERINE AND THREONINE 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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION

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	NEIL1	NEIL1	NEIL1	438	0.44	0.13	YES
2	LIG1	LIG1	LIG1	4045	0.15	-0.009	YES
3	MUTYH	MUTYH	MUTYH	4139	0.14	0.038	YES
4	UNG	UNG	UNG	4789	0.12	0.048	YES
5	NEIL3	NEIL3	NEIL3	4966	0.12	0.082	YES
6	POLE2	POLE2	POLE2	5004	0.12	0.12	YES
7	OGG1	OGG1	OGG1	5075	0.12	0.16	YES
8	PARP1	PARP1	PARP1	5155	0.12	0.2	YES
9	POLB	POLB	POLB	5548	0.1	0.21	YES
10	MBD4	MBD4	MBD4	5679	0.1	0.24	YES
11	POLE	POLE	POLE	5732	0.099	0.28	YES
12	NTHL1	NTHL1	NTHL1	5860	0.095	0.3	YES
13	XRCC1	XRCC1	XRCC1	5944	0.093	0.33	YES
14	PCNA	PCNA	PCNA	6208	0.087	0.35	YES
15	LIG3	LIG3	LIG3	6461	0.081	0.36	YES
16	FEN1	FEN1	FEN1	6756	0.075	0.38	YES
17	POLD3	POLD3	POLD3	6900	0.072	0.39	YES
18	PARP3	PARP3	PARP3	7000	0.07	0.41	YES
19	PARP2	PARP2	PARP2	7036	0.069	0.44	YES
20	PARP4	PARP4	PARP4	7558	0.059	0.43	YES
21	POLD1	POLD1	POLD1	7625	0.058	0.45	YES
22	NEIL2	NEIL2	NEIL2	8351	0.046	0.42	NO
23	POLE3	POLE3	POLE3	8503	0.044	0.43	NO
24	APEX1	APEX1	APEX1	8986	0.037	0.42	NO
25	POLL	POLL	POLL	9298	0.032	0.41	NO
26	SMUG1	SMUG1	SMUG1	9880	0.024	0.39	NO
27	APEX2	APEX2	APEX2	11364	0.0038	0.31	NO
28	POLD2	POLD2	POLD2	12781	-0.016	0.24	NO
29	TDG	TDG	TDG	12983	-0.02	0.24	NO
30	MPG	MPG	MPG	13701	-0.033	0.21	NO
31	POLE4	POLE4	POLE4	14227	-0.044	0.2	NO
32	POLD4	POLD4	POLD4	15747	-0.085	0.14	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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE 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 LYSINE DEGRADATION

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	GSTA1	GSTA1	GSTA1	133	0.54	0.038	YES
2	UGT1A9	UGT1A9	UGT1A9	272	0.48	0.07	YES
3	UGT1A6	UGT1A6	UGT1A6	273	0.48	0.11	YES
4	GSTA2	GSTA2	GSTA2	359	0.46	0.14	YES
5	UGT2A1	UGT2A1	UGT2A1	375	0.45	0.18	YES
6	ADH1C	ADH1C	ADH1C	436	0.44	0.22	YES
7	ADH6	ADH6	ADH6	496	0.43	0.25	YES
8	CYP2F1	CYP2F1	CYP2F1	526	0.42	0.28	YES
9	UGT1A8	UGT1A8	UGT1A8	623	0.4	0.31	YES
10	UGT1A3	UGT1A3	UGT1A3	659	0.39	0.34	YES
11	ADH7	ADH7	ADH7	689	0.39	0.37	YES
12	ALDH3A1	ALDH3A1	ALDH3A1	702	0.39	0.4	YES
13	UGT1A7	UGT1A7	UGT1A7	1113	0.33	0.41	YES
14	GSTM4	GSTM4	GSTM4	1386	0.3	0.42	YES
15	UGT1A4	UGT1A4	UGT1A4	1434	0.3	0.44	YES
16	CYP2E1	CYP2E1	CYP2E1	1544	0.29	0.46	YES
17	MGST1	MGST1	MGST1	1604	0.28	0.48	YES
18	CYP2S1	CYP2S1	CYP2S1	1627	0.28	0.5	YES
19	GSTM2	GSTM2	GSTM2	1670	0.28	0.52	YES
20	GSTM3	GSTM3	GSTM3	1959	0.26	0.53	YES
21	EPHX1	EPHX1	EPHX1	2157	0.24	0.54	YES
22	CYP1B1	CYP1B1	CYP1B1	2288	0.24	0.55	YES
23	CYP2C19	CYP2C19	CYP2C19	2389	0.23	0.56	YES
24	UGT1A10	UGT1A10	UGT1A10	2604	0.22	0.57	YES
25	CYP2C9	CYP2C9	CYP2C9	2900	0.2	0.57	YES
26	UGT1A1	UGT1A1	UGT1A1	2934	0.2	0.59	YES
27	UGT2B15	UGT2B15	UGT2B15	2960	0.2	0.6	YES
28	DHDH	DHDH	DHDH	3112	0.19	0.61	YES
29	CYP3A5	CYP3A5	CYP3A5	3334	0.18	0.61	YES
30	AKR1C1	AKR1C1	AKR1C1	3407	0.17	0.62	YES
31	CYP3A7	CYP3A7	CYP3A7	3790	0.16	0.61	YES
32	ADH1A	ADH1A	ADH1A	4365	0.14	0.59	YES
33	CYP1A1	CYP1A1	CYP1A1	4512	0.13	0.6	YES
34	GSTA3	GSTA3	GSTA3	4563	0.13	0.6	YES
35	CYP2B6	CYP2B6	CYP2B6	4747	0.13	0.61	YES
36	AKR1C3	AKR1C3	AKR1C3	4804	0.12	0.61	YES
37	GSTA4	GSTA4	GSTA4	4888	0.12	0.62	YES
38	AKR1C2	AKR1C2	AKR1C2	4939	0.12	0.63	YES
39	UGT2B7	UGT2B7	UGT2B7	4986	0.12	0.63	YES
40	ALDH3B1	ALDH3B1	ALDH3B1	6234	0.086	0.57	NO
41	MGST2	MGST2	MGST2	6540	0.08	0.56	NO
42	GSTM1	GSTM1	GSTM1	6752	0.075	0.56	NO
43	GSTT1	GSTT1	GSTT1	6832	0.074	0.56	NO
44	CYP2C8	CYP2C8	CYP2C8	7657	0.058	0.52	NO
45	CYP2C18	CYP2C18	CYP2C18	7769	0.056	0.52	NO
46	GSTT2	GSTT2	GSTT2	7874	0.054	0.52	NO
47	MGST3	MGST3	MGST3	8523	0.043	0.48	NO
48	GSTM5	GSTM5	GSTM5	8648	0.042	0.48	NO
49	ADH5	ADH5	ADH5	8935	0.037	0.47	NO
50	ADH1B	ADH1B	ADH1B	9668	0.027	0.43	NO
51	ADH4	ADH4	ADH4	9841	0.025	0.42	NO
52	GSTO2	GSTO2	GSTO2	9977	0.023	0.42	NO
53	GSTZ1	GSTZ1	GSTZ1	11299	0.0047	0.35	NO
54	GSTK1	GSTK1	GSTK1	14141	-0.042	0.2	NO
55	GSTO1	GSTO1	GSTO1	14222	-0.044	0.19	NO
56	GSTP1	GSTP1	GSTP1	14499	-0.05	0.18	NO
57	ALDH1A3	ALDH1A3	ALDH1A3	15336	-0.072	0.14	NO
58	ALDH3B2	ALDH3B2	ALDH3B2	17620	-0.26	0.04	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 LYSINE DEGRADATION.

Figure S32. 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 SELENOAMINO ACID METABOLISM

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	ACADSB	ACADSB	ACADSB	1480	0.29	-0.014	YES
2	IVD	IVD	IVD	1560	0.29	0.047	YES
3	ALDH6A1	ALDH6A1	ALDH6A1	1714	0.28	0.1	YES
4	BCKDHB	BCKDHB	BCKDHB	1761	0.27	0.16	YES
5	ABAT	ABAT	ABAT	2066	0.25	0.2	YES
6	MCCC1	MCCC1	MCCC1	2230	0.24	0.25	YES
7	PCCA	PCCA	PCCA	3147	0.19	0.24	YES
8	ACAT2	ACAT2	ACAT2	3579	0.17	0.25	YES
9	BCAT2	BCAT2	BCAT2	3620	0.16	0.29	YES
10	PCCB	PCCB	PCCB	4371	0.14	0.28	YES
11	IL4I1	IL4I1	IL4I1	4635	0.13	0.29	YES
12	HADH	HADH	HADH	4726	0.13	0.32	YES
13	ACADS	ACADS	ACADS	4926	0.12	0.33	YES
14	ALDH3A2	ALDH3A2	ALDH3A2	5247	0.11	0.34	YES
15	EHHADH	EHHADH	EHHADH	5589	0.1	0.35	YES
16	OXCT2	OXCT2	OXCT2	5606	0.1	0.37	YES
17	HMGCS2	HMGCS2	HMGCS2	5844	0.096	0.38	YES
18	MCCC2	MCCC2	MCCC2	6068	0.09	0.39	YES
19	ACADM	ACADM	ACADM	6248	0.086	0.4	YES
20	HIBADH	HIBADH	HIBADH	6399	0.082	0.41	YES
21	AUH	AUH	AUH	6666	0.077	0.41	YES
22	ALDH1B1	ALDH1B1	ALDH1B1	7044	0.069	0.4	YES
23	HIBCH	HIBCH	HIBCH	7330	0.064	0.4	YES
24	DBT	DBT	DBT	7461	0.061	0.41	YES
25	ACAD8	ACAD8	ACAD8	7741	0.056	0.41	NO
26	BCKDHA	BCKDHA	BCKDHA	7977	0.052	0.41	NO
27	DLD	DLD	DLD	8562	0.043	0.38	NO
28	OXCT1	OXCT1	OXCT1	8937	0.037	0.37	NO
29	ALDH9A1	ALDH9A1	ALDH9A1	8995	0.036	0.38	NO
30	ALDH2	ALDH2	ALDH2	9500	0.03	0.36	NO
31	MUT	MUT	MUT	9727	0.026	0.35	NO
32	MCEE	MCEE	MCEE	9789	0.026	0.35	NO
33	HSD17B10	HSD17B10	HSD17B10	10360	0.017	0.33	NO
34	ECHS1	ECHS1	ECHS1	10431	0.017	0.33	NO
35	ACAT1	ACAT1	ACAT1	11395	0.0035	0.27	NO
36	ACAA2	ACAA2	ACAA2	11529	0.0017	0.27	NO
37	HMGCS1	HMGCS1	HMGCS1	11731	-0.001	0.26	NO
38	HADHB	HADHB	HADHB	12856	-0.018	0.2	NO
39	HMGCL	HMGCL	HMGCL	13123	-0.022	0.19	NO
40	HADHA	HADHA	HADHA	13565	-0.03	0.17	NO
41	ACAA1	ACAA1	ACAA1	15851	-0.09	0.068	NO
42	AOX1	AOX1	AOX1	16187	-0.1	0.074	NO
43	ALDH7A1	ALDH7A1	ALDH7A1	17263	-0.2	0.06	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 SELENOAMINO ACID METABOLISM.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SELENOAMINO 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 STARCH AND SUCROSE METABOLISM

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	GSTA1	GSTA1	GSTA1	133	0.54	0.038	YES
2	UGT1A9	UGT1A9	UGT1A9	272	0.48	0.07	YES
3	UGT1A6	UGT1A6	UGT1A6	273	0.48	0.11	YES
4	GSTA2	GSTA2	GSTA2	359	0.46	0.14	YES
5	UGT2A1	UGT2A1	UGT2A1	375	0.45	0.18	YES
6	ADH1C	ADH1C	ADH1C	436	0.44	0.22	YES
7	ADH6	ADH6	ADH6	496	0.43	0.25	YES
8	UGT1A8	UGT1A8	UGT1A8	623	0.4	0.27	YES
9	UGT1A3	UGT1A3	UGT1A3	659	0.39	0.31	YES
10	ADH7	ADH7	ADH7	689	0.39	0.34	YES
11	ALDH3A1	ALDH3A1	ALDH3A1	702	0.39	0.37	YES
12	UGT1A7	UGT1A7	UGT1A7	1113	0.33	0.37	YES
13	FMO3	FMO3	FMO3	1137	0.33	0.4	YES
14	CYP2A6	CYP2A6	CYP2A6	1163	0.32	0.43	YES
15	GSTM4	GSTM4	GSTM4	1386	0.3	0.44	YES
16	UGT1A4	UGT1A4	UGT1A4	1434	0.3	0.46	YES
17	CYP2D6	CYP2D6	CYP2D6	1517	0.29	0.48	YES
18	MAOB	MAOB	MAOB	1534	0.29	0.5	YES
19	CYP2E1	CYP2E1	CYP2E1	1544	0.29	0.53	YES
20	MGST1	MGST1	MGST1	1604	0.28	0.55	YES
21	GSTM2	GSTM2	GSTM2	1670	0.28	0.57	YES
22	GSTM3	GSTM3	GSTM3	1959	0.26	0.57	YES
23	CYP2C19	CYP2C19	CYP2C19	2389	0.23	0.57	YES
24	UGT1A10	UGT1A10	UGT1A10	2604	0.22	0.58	YES
25	CYP2C9	CYP2C9	CYP2C9	2900	0.2	0.58	YES
26	UGT1A1	UGT1A1	UGT1A1	2934	0.2	0.59	YES
27	UGT2B15	UGT2B15	UGT2B15	2960	0.2	0.61	YES
28	MAOA	MAOA	MAOA	3014	0.19	0.62	YES
29	CYP3A5	CYP3A5	CYP3A5	3334	0.18	0.62	NO
30	CYP3A7	CYP3A7	CYP3A7	3790	0.16	0.61	NO
31	ADH1A	ADH1A	ADH1A	4365	0.14	0.59	NO
32	GSTA3	GSTA3	GSTA3	4563	0.13	0.59	NO
33	CYP2B6	CYP2B6	CYP2B6	4747	0.13	0.59	NO
34	GSTA4	GSTA4	GSTA4	4888	0.12	0.59	NO
35	UGT2B7	UGT2B7	UGT2B7	4986	0.12	0.59	NO
36	FMO5	FMO5	FMO5	5448	0.11	0.58	NO
37	FMO2	FMO2	FMO2	5643	0.1	0.58	NO
38	ALDH3B1	ALDH3B1	ALDH3B1	6234	0.086	0.55	NO
39	MGST2	MGST2	MGST2	6540	0.08	0.54	NO
40	GSTM1	GSTM1	GSTM1	6752	0.075	0.54	NO
41	GSTT1	GSTT1	GSTT1	6832	0.074	0.54	NO
42	FMO4	FMO4	FMO4	7466	0.061	0.51	NO
43	CYP2C8	CYP2C8	CYP2C8	7657	0.058	0.5	NO
44	CYP2C18	CYP2C18	CYP2C18	7769	0.056	0.5	NO
45	GSTT2	GSTT2	GSTT2	7874	0.054	0.5	NO
46	MGST3	MGST3	MGST3	8523	0.043	0.47	NO
47	GSTM5	GSTM5	GSTM5	8648	0.042	0.46	NO
48	ADH5	ADH5	ADH5	8935	0.037	0.45	NO
49	ADH1B	ADH1B	ADH1B	9668	0.027	0.42	NO
50	ADH4	ADH4	ADH4	9841	0.025	0.41	NO
51	GSTO2	GSTO2	GSTO2	9977	0.023	0.4	NO
52	GSTZ1	GSTZ1	GSTZ1	11299	0.0047	0.33	NO
53	GSTK1	GSTK1	GSTK1	14141	-0.042	0.18	NO
54	GSTO1	GSTO1	GSTO1	14222	-0.044	0.18	NO
55	GSTP1	GSTP1	GSTP1	14499	-0.05	0.17	NO
56	ALDH1A3	ALDH1A3	ALDH1A3	15336	-0.072	0.13	NO
57	FMO1	FMO1	FMO1	15834	-0.089	0.11	NO
58	AOX1	AOX1	AOX1	16187	-0.1	0.097	NO
59	ALDH3B2	ALDH3B2	ALDH3B2	17620	-0.26	0.04	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 STARCH AND SUCROSE METABOLISM.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG STARCH AND SUCROSE 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 GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES

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	CACNA1B	CACNA1B	CACNA1B	65	0.59	0.095	YES
2	GNB3	GNB3	GNB3	607	0.4	0.13	YES
3	GNG3	GNG3	GNG3	1172	0.32	0.16	YES
4	PRKX	PRKX	PRKX	1245	0.32	0.2	YES
5	TAS2R19	TAS2R19	TAS2R19	1615	0.28	0.23	YES
6	TAS2R20	TAS2R20	TAS2R20	1640	0.28	0.28	YES
7	TAS2R31	TAS2R31	TAS2R31	1654	0.28	0.32	YES
8	TRPM5	TRPM5	TRPM5	1887	0.26	0.36	YES
9	TAS1R3	TAS1R3	TAS1R3	2005	0.25	0.39	YES
10	SCNN1A	SCNN1A	SCNN1A	2218	0.24	0.42	YES
11	TAS2R14	TAS2R14	TAS2R14	2223	0.24	0.46	YES
12	ADCY6	ADCY6	ADCY6	2300	0.24	0.49	YES
13	TAS2R43	TAS2R43	TAS2R43	2748	0.21	0.5	YES
14	TAS2R4	TAS2R4	TAS2R4	2802	0.2	0.54	YES
15	SCNN1B	SCNN1B	SCNN1B	3268	0.18	0.54	YES
16	PLCB2	PLCB2	PLCB2	3703	0.16	0.54	YES
17	TAS1R1	TAS1R1	TAS1R1	3897	0.15	0.56	YES
18	TAS2R10	TAS2R10	TAS2R10	4044	0.15	0.57	YES
19	TAS2R5	TAS2R5	TAS2R5	4335	0.14	0.58	YES
20	ADCY8	ADCY8	ADCY8	4769	0.13	0.58	NO
21	SCNN1G	SCNN1G	SCNN1G	6077	0.09	0.52	NO
22	TAS2R13	TAS2R13	TAS2R13	6611	0.078	0.51	NO
23	TAS2R38	TAS2R38	TAS2R38	8962	0.037	0.39	NO
24	PDE1A	PDE1A	PDE1A	9282	0.033	0.37	NO
25	GNAS	GNAS	GNAS	9615	0.028	0.36	NO
26	PRKACA	PRKACA	PRKACA	9901	0.024	0.35	NO
27	CACNA1A	CACNA1A	CACNA1A	10676	0.013	0.31	NO
28	PRKACB	PRKACB	PRKACB	12398	-0.011	0.22	NO
29	ITPR3	ITPR3	ITPR3	13558	-0.03	0.16	NO
30	GNB1	GNB1	GNB1	13847	-0.036	0.15	NO
31	GRM4	GRM4	GRM4	14111	-0.041	0.14	NO
32	ACCN1	ACCN1	ACCN1	14657	-0.053	0.12	NO
33	ADCY4	ADCY4	ADCY4	14723	-0.055	0.13	NO
34	KCNB1	KCNB1	KCNB1	17035	-0.17	0.028	NO
35	TAS2R60	TAS2R60	TAS2R60	17667	-0.27	0.038	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 GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, 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 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	SMC1B	SMC1B	SMC1B	219	0.5	0.029	YES
2	E2F5	E2F5	E2F5	238	0.49	0.068	YES
3	CDKN2C	CDKN2C	CDKN2C	1029	0.34	0.053	YES
4	WEE2	WEE2	WEE2	1518	0.29	0.05	YES
5	CDC14A	CDC14A	CDC14A	1595	0.28	0.069	YES
6	TFDP2	TFDP2	TFDP2	1865	0.26	0.076	YES
7	CCNB3	CCNB3	CCNB3	1879	0.26	0.097	YES
8	CDKN2A	CDKN2A	CDKN2A	2313	0.23	0.092	YES
9	CDC7	CDC7	CDC7	2720	0.21	0.087	YES
10	E2F1	E2F1	E2F1	2800	0.2	0.099	YES
11	CDC25C	CDC25C	CDC25C	2816	0.2	0.12	YES
12	TP53	TP53	TP53	2938	0.2	0.12	YES
13	E2F2	E2F2	E2F2	2982	0.19	0.14	YES
14	MCM2	MCM2	MCM2	3126	0.19	0.14	YES
15	CHEK2	CHEK2	CHEK2	3153	0.19	0.16	YES
16	ESPL1	ESPL1	ESPL1	3323	0.18	0.16	YES
17	CCNE2	CCNE2	CCNE2	3474	0.17	0.17	YES
18	CDC14B	CDC14B	CDC14B	3512	0.17	0.18	YES
19	PTTG2	PTTG2	PTTG2	3610	0.16	0.19	YES
20	ORC1L	ORC1L	ORC1L	3765	0.16	0.2	YES
21	CDC45	CDC45	CDC45	3819	0.16	0.2	YES
22	CDC25A	CDC25A	CDC25A	3906	0.15	0.21	YES
23	CDK1	CDK1	CDK1	4272	0.14	0.2	YES
24	MCM6	MCM6	MCM6	4298	0.14	0.21	YES
25	BUB1B	BUB1B	BUB1B	4333	0.14	0.22	YES
26	CDC6	CDC6	CDC6	4390	0.14	0.23	YES
27	MCM5	MCM5	MCM5	4576	0.13	0.23	YES
28	MAD2L1	MAD2L1	MAD2L1	4677	0.13	0.24	YES
29	MCM7	MCM7	MCM7	4758	0.13	0.24	YES
30	MCM3	MCM3	MCM3	5009	0.12	0.24	YES
31	ATR	ATR	ATR	5114	0.12	0.24	YES
32	CDKN1B	CDKN1B	CDKN1B	5142	0.12	0.25	YES
33	TTK	TTK	TTK	5189	0.11	0.26	YES
34	STAG1	STAG1	STAG1	5198	0.11	0.27	YES
35	ORC6L	ORC6L	ORC6L	5264	0.11	0.27	YES
36	RBL1	RBL1	RBL1	5280	0.11	0.28	YES
37	MDM2	MDM2	MDM2	5379	0.11	0.28	YES
38	CDK2	CDK2	CDK2	5512	0.1	0.28	YES
39	SMAD4	SMAD4	SMAD4	5530	0.1	0.29	YES
40	WEE1	WEE1	WEE1	5555	0.1	0.3	YES
41	SMAD2	SMAD2	SMAD2	5785	0.098	0.3	YES
42	GADD45G	GADD45G	GADD45G	5882	0.095	0.3	YES
43	ORC2L	ORC2L	ORC2L	5914	0.094	0.3	YES
44	ATM	ATM	ATM	6023	0.091	0.3	YES
45	CCNB2	CCNB2	CCNB2	6069	0.09	0.31	YES
46	CDK4	CDK4	CDK4	6105	0.089	0.32	YES
47	PCNA	PCNA	PCNA	6208	0.087	0.32	YES
48	BUB1	BUB1	BUB1	6221	0.087	0.32	YES
49	CDKN1C	CDKN1C	CDKN1C	6408	0.082	0.32	YES
50	CCNA2	CCNA2	CCNA2	6507	0.08	0.32	YES
51	CDKN2D	CDKN2D	CDKN2D	6603	0.078	0.32	YES
52	ORC4L	ORC4L	ORC4L	6699	0.076	0.32	YES
53	HDAC2	HDAC2	HDAC2	6706	0.076	0.33	YES
54	SMAD3	SMAD3	SMAD3	6743	0.075	0.33	YES
55	ORC3L	ORC3L	ORC3L	6759	0.075	0.34	YES
56	ANAPC7	ANAPC7	ANAPC7	6760	0.075	0.34	YES
57	SMC3	SMC3	SMC3	7233	0.066	0.32	NO
58	ANAPC10	ANAPC10	ANAPC10	7570	0.059	0.31	NO
59	SMC1A	SMC1A	SMC1A	7614	0.058	0.31	NO
60	MCM4	MCM4	MCM4	7643	0.058	0.32	NO
61	SKP2	SKP2	SKP2	7678	0.057	0.32	NO
62	PTTG1	PTTG1	PTTG1	7762	0.056	0.32	NO
63	CHEK1	CHEK1	CHEK1	7812	0.055	0.32	NO
64	CDC26	CDC26	CDC26	7903	0.053	0.32	NO
65	ANAPC1	ANAPC1	ANAPC1	7963	0.052	0.32	NO
66	ORC5L	ORC5L	ORC5L	8248	0.047	0.31	NO
67	E2F3	E2F3	E2F3	8378	0.046	0.31	NO
68	EP300	EP300	EP300	8457	0.044	0.31	NO
69	STAG2	STAG2	STAG2	8501	0.044	0.31	NO
70	CREBBP	CREBBP	CREBBP	8581	0.043	0.31	NO
71	RAD21	RAD21	RAD21	8991	0.037	0.29	NO
72	PLK1	PLK1	PLK1	9036	0.036	0.29	NO
73	CCNB1	CCNB1	CCNB1	9168	0.034	0.28	NO
74	CDC23	CDC23	CDC23	9278	0.033	0.28	NO
75	CCNE1	CCNE1	CCNE1	9669	0.027	0.26	NO
76	ANAPC5	ANAPC5	ANAPC5	9747	0.026	0.26	NO
77	CCNH	CCNH	CCNH	9826	0.025	0.26	NO
78	RBL2	RBL2	RBL2	9873	0.024	0.26	NO
79	HDAC1	HDAC1	HDAC1	10180	0.02	0.24	NO
80	GSK3B	GSK3B	GSK3B	10297	0.018	0.24	NO
81	FZR1	FZR1	FZR1	10370	0.017	0.23	NO
82	PRKDC	PRKDC	PRKDC	10417	0.017	0.23	NO
83	ANAPC13	ANAPC13	ANAPC13	10459	0.016	0.23	NO
84	CCND3	CCND3	CCND3	10476	0.016	0.23	NO
85	ANAPC11	ANAPC11	ANAPC11	10601	0.014	0.23	NO
86	BUB3	BUB3	BUB3	10638	0.014	0.22	NO
87	ABL1	ABL1	ABL1	11281	0.005	0.19	NO
88	YWHAH	YWHAH	YWHAH	11375	0.0037	0.18	NO
89	ANAPC2	ANAPC2	ANAPC2	11577	0.0011	0.17	NO
90	CUL1	CUL1	CUL1	11611	0.0006	0.17	NO
91	PKMYT1	PKMYT1	PKMYT1	11627	0.00031	0.17	NO
92	SKP1	SKP1	SKP1	11726	-0.00091	0.17	NO
93	ANAPC4	ANAPC4	ANAPC4	12107	-0.0066	0.15	NO
94	YWHAE	YWHAE	YWHAE	12294	-0.0091	0.14	NO
95	TFDP1	TFDP1	TFDP1	12352	-0.01	0.14	NO
96	MAD2L2	MAD2L2	MAD2L2	12442	-0.011	0.13	NO
97	CDC20	CDC20	CDC20	12639	-0.014	0.12	NO
98	RBX1	RBX1	RBX1	13095	-0.022	0.098	NO
99	YWHAG	YWHAG	YWHAG	13564	-0.03	0.075	NO
100	CDKN2B	CDKN2B	CDKN2B	13773	-0.034	0.066	NO
101	CDC27	CDC27	CDC27	14156	-0.042	0.048	NO
102	GADD45A	GADD45A	GADD45A	14208	-0.043	0.049	NO
103	E2F4	E2F4	E2F4	14217	-0.044	0.052	NO
104	YWHAQ	YWHAQ	YWHAQ	14344	-0.046	0.049	NO
105	CCND2	CCND2	CCND2	14468	-0.049	0.046	NO
106	CDC16	CDC16	CDC16	14606	-0.052	0.043	NO
107	RB1	RB1	RB1	14607	-0.052	0.048	NO
108	CCND1	CCND1	CCND1	14631	-0.052	0.05	NO
109	YWHAB	YWHAB	YWHAB	14736	-0.055	0.049	NO
110	ZBTB17	ZBTB17	ZBTB17	14764	-0.056	0.052	NO
111	MYC	MYC	MYC	14874	-0.058	0.051	NO
112	MAD1L1	MAD1L1	MAD1L1	14943	-0.06	0.052	NO
113	CDK7	CDK7	CDK7	15570	-0.079	0.024	NO
114	GADD45B	GADD45B	GADD45B	15927	-0.093	0.013	NO
115	YWHAZ	YWHAZ	YWHAZ	16009	-0.096	0.016	NO
116	CDC25B	CDC25B	CDC25B	16117	-0.1	0.018	NO
117	TGFB3	TGFB3	TGFB3	16310	-0.11	0.017	NO
118	TGFB1	TGFB1	TGFB1	16576	-0.13	0.013	NO
119	CDKN1A	CDKN1A	CDKN1A	16627	-0.13	0.021	NO
120	TGFB2	TGFB2	TGFB2	16937	-0.16	0.017	NO
121	CDK6	CDK6	CDK6	17185	-0.19	0.019	NO
122	SFN	SFN	SFN	17381	-0.21	0.026	NO
123	CCNA1	CCNA1	CCNA1	17935	-0.34	0.023	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 BUTANOATE METABOLISM.

Figure S40. 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

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
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.24	0.78	0.72	1	1	0.22	0.13	0.19	1	0.63
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.28	1.2	0.27	0.9	1	0.2	0.1	0.18	0.82	0.35
BIOCARTA PYK2 PATHWAY	27	genes.ES.table	0.23	0.89	0.58	0.98	1	0.3	0.16	0.25	0.97	0.45
BIOCARTA IL1R PATHWAY	32	genes.ES.table	0.34	0.97	0.51	0.97	1	0.34	0.16	0.29	0.93	0.42
KEGG PYRIMIDINE METABOLISM	96	genes.ES.table	0.21	0.94	0.5	0.98	1	0.083	0.056	0.079	0.95	0.44
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	42	genes.ES.table	0.21	0.83	0.68	1	1	0.21	0.1	0.19	1	0.59
KEGG ETHER LIPID METABOLISM	28	genes.ES.table	0.32	0.94	0.54	0.93	1	0.18	0.044	0.17	0.9	0.36
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.35	1.4	0.13	0.74	0.97	1	0.65	0.35	0.57	0.26
KEGG RIBOSOME	85	genes.ES.table	0.61	1.5	0.12	0.53	0.87	0.88	0.26	0.65	0.35	0.15
KEGG RNA POLYMERASE	28	genes.ES.table	0.28	0.99	0.42	1	1	0.93	0.49	0.48	0.97	0.46

genes ES table in pathway: BIOCARTA ERK PATHWAY

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	PSMB8	PSMB8	PSMB8	2091	0.076	-0.068	YES
2	PSMD6	PSMD6	PSMD6	2137	0.074	-0.025	YES
3	PSME2	PSME2	PSME2	2249	0.07	0.011	YES
4	PSMA5	PSMA5	PSMA5	2268	0.069	0.053	YES
5	PSMB7	PSMB7	PSMB7	2306	0.068	0.092	YES
6	POMP	POMP	POMP	2338	0.067	0.13	YES
7	PSMD13	PSMD13	PSMD13	2351	0.067	0.17	YES
8	PSMA6	PSMA6	PSMA6	2698	0.056	0.19	YES
9	PSMB5	PSMB5	PSMB5	2859	0.051	0.21	YES
10	PSMC1	PSMC1	PSMC1	2867	0.051	0.24	YES
11	PSMB2	PSMB2	PSMB2	3058	0.047	0.26	YES
12	PSMB6	PSMB6	PSMB6	3119	0.045	0.28	YES
13	PSME1	PSME1	PSME1	3153	0.044	0.31	YES
14	PSMD12	PSMD12	PSMD12	3309	0.042	0.32	YES
15	PSMA4	PSMA4	PSMA4	3381	0.04	0.34	YES
16	PSMA3	PSMA3	PSMA3	3420	0.039	0.37	YES
17	PSMB9	PSMB9	PSMB9	3422	0.039	0.39	YES
18	PSMC3	PSMC3	PSMC3	3447	0.039	0.41	YES
19	PSMA2	PSMA2	PSMA2	3506	0.037	0.43	YES
20	PSMD7	PSMD7	PSMD7	3556	0.037	0.45	YES
21	PSMC6	PSMC6	PSMC6	3690	0.034	0.47	YES
22	PSMA7	PSMA7	PSMA7	3708	0.034	0.48	YES
23	PSMB1	PSMB1	PSMB1	3744	0.033	0.5	YES
24	PSMD8	PSMD8	PSMD8	3803	0.032	0.52	YES
25	PSME3	PSME3	PSME3	3808	0.032	0.54	YES
26	PSMD1	PSMD1	PSMD1	3936	0.03	0.55	YES
27	PSMB3	PSMB3	PSMB3	3967	0.029	0.57	YES
28	PSMF1	PSMF1	PSMF1	4007	0.029	0.58	YES
29	PSMA1	PSMA1	PSMA1	4123	0.027	0.59	YES
30	PSMC5	PSMC5	PSMC5	4556	0.019	0.58	YES
31	SHFM1	SHFM1	SHFM1	4790	0.016	0.58	YES
32	PSMD3	PSMD3	PSMD3	4845	0.015	0.58	YES
33	PSMD14	PSMD14	PSMD14	4877	0.014	0.59	YES
34	IFNG	IFNG	IFNG	4938	0.013	0.6	YES
35	PSMD4	PSMD4	PSMD4	5211	0.0085	0.58	NO
36	PSMC4	PSMC4	PSMC4	5296	0.0071	0.58	NO
37	PSMD11	PSMD11	PSMD11	5850	-0.0014	0.56	NO
38	PSMB4	PSMB4	PSMB4	6201	-0.0067	0.54	NO
39	PSMC2	PSMC2	PSMC2	6286	-0.0078	0.54	NO
40	PSMD2	PSMD2	PSMD2	6862	-0.016	0.52	NO
41	PSME4	PSME4	PSME4	7400	-0.025	0.5	NO
42	PSMA8	PSMA8	PSMA8	13189	-0.15	0.28	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: BIOCARTA ERK PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ERK 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 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	IL1B	IL1B	IL1B	320	0.31	0.074	YES
2	IL18	IL18	IL18	334	0.31	0.16	YES
3	POLR3G	POLR3G	POLR3G	394	0.28	0.24	YES
4	AIM2	AIM2	AIM2	604	0.22	0.29	YES
5	CASP1	CASP1	CASP1	698	0.19	0.35	YES
6	IRF7	IRF7	IRF7	711	0.19	0.4	YES
7	PYCARD	PYCARD	PYCARD	720	0.19	0.46	YES
8	IFNA13	IFNA13	IFNA13	806	0.18	0.5	YES
9	DDX58	DDX58	DDX58	890	0.16	0.55	YES
10	IFNA1	IFNA1	IFNA1	975	0.15	0.59	YES
11	CXCL10	CXCL10	CXCL10	1283	0.12	0.61	YES
12	ZBP1	ZBP1	ZBP1	1680	0.094	0.61	YES
13	RIPK3	RIPK3	RIPK3	2846	0.052	0.56	NO
14	CCL5	CCL5	CCL5	2944	0.05	0.57	NO
15	POLR1D	POLR1D	POLR1D	3240	0.043	0.57	NO
16	POLR3B	POLR3B	POLR3B	3363	0.04	0.57	NO
17	POLR3H	POLR3H	POLR3H	3557	0.036	0.57	NO
18	RELA	RELA	RELA	4106	0.027	0.55	NO
19	IRF3	IRF3	IRF3	4414	0.022	0.54	NO
20	NFKBIB	NFKBIB	NFKBIB	4421	0.021	0.55	NO
21	POLR3A	POLR3A	POLR3A	4660	0.018	0.54	NO
22	RIPK1	RIPK1	RIPK1	5029	0.012	0.52	NO
23	POLR1C	POLR1C	POLR1C	5148	0.0095	0.52	NO
24	IFNB1	IFNB1	IFNB1	5165	0.0092	0.52	NO
25	NFKBIA	NFKBIA	NFKBIA	5419	0.0052	0.51	NO
26	NFKB1	NFKB1	NFKB1	5544	0.0032	0.5	NO
27	IL33	IL33	IL33	5889	-0.0019	0.49	NO
28	IKBKG	IKBKG	IKBKG	5923	-0.0025	0.48	NO
29	CHUK	CHUK	CHUK	6098	-0.0053	0.48	NO
30	TMEM173	TMEM173	TMEM173	6311	-0.0082	0.47	NO
31	ADAR	ADAR	ADAR	6661	-0.013	0.45	NO
32	POLR3F	POLR3F	POLR3F	6687	-0.014	0.46	NO
33	CCL4	CCL4	CCL4	7340	-0.024	0.43	NO
34	TREX1	TREX1	TREX1	7833	-0.031	0.41	NO
35	IL6	IL6	IL6	7998	-0.034	0.41	NO
36	POLR3K	POLR3K	POLR3K	8109	-0.036	0.41	NO
37	MAVS	MAVS	MAVS	8501	-0.042	0.4	NO
38	TBK1	TBK1	TBK1	8519	-0.042	0.42	NO
39	IKBKE	IKBKE	IKBKE	8737	-0.046	0.42	NO
40	POLR3C	POLR3C	POLR3C	8821	-0.047	0.43	NO
41	POLR3D	POLR3D	POLR3D	8956	-0.05	0.43	NO
42	IKBKB	IKBKB	IKBKB	9933	-0.068	0.4	NO
43	CCL4L2	CCL4L2	CCL4L2	10514	-0.08	0.39	NO
44	POLR3GL	POLR3GL	POLR3GL	12195	-0.12	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: BIOCARTA RACCYCD PATHWAY.

Figure S44. 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 PYK2 PATHWAY

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	RPL36A	RPL36A	RPL36A	1134	0.13	-0.024	YES
2	RPL39	RPL39	RPL39	1913	0.082	-0.044	YES
3	RPL36AL	RPL36AL	RPL36AL	1932	0.082	-0.022	YES
4	RPL9	RPL9	RPL9	2039	0.078	-0.0057	YES
5	RPLP2	RPLP2	RPLP2	2290	0.069	0.000021	YES
6	RPL22L1	RPL22L1	RPL22L1	2305	0.068	0.018	YES
7	RPS13	RPS13	RPS13	2372	0.066	0.034	YES
8	RPL35	RPL35	RPL35	2380	0.066	0.052	YES
9	RPL29	RPL29	RPL29	2397	0.065	0.069	YES
10	RPL27A	RPL27A	RPL27A	2447	0.064	0.084	YES
11	RPL11	RPL11	RPL11	2579	0.059	0.094	YES
12	RPL18A	RPL18A	RPL18A	2585	0.059	0.11	YES
13	RPS3	RPS3	RPS3	2621	0.058	0.12	YES
14	RPL36	RPL36	RPL36	2653	0.057	0.14	YES
15	RPL38	RPL38	RPL38	2684	0.056	0.15	YES
16	RPL26L1	RPL26L1	RPL26L1	2807	0.053	0.16	YES
17	RPS10	RPS10	RPS10	2812	0.052	0.18	YES
18	RPS12	RPS12	RPS12	2833	0.052	0.19	YES
19	RPS29	RPS29	RPS29	2848	0.052	0.2	YES
20	RPS2	RPS2	RPS2	2902	0.05	0.21	YES
21	MRPL13	MRPL13	MRPL13	2930	0.05	0.23	YES
22	RPS15	RPS15	RPS15	2938	0.05	0.24	YES
23	RPL34	RPL34	RPL34	2949	0.049	0.25	YES
24	RPL27	RPL27	RPL27	2964	0.049	0.27	YES
25	RPS16	RPS16	RPS16	2976	0.049	0.28	YES
26	RPL14	RPL14	RPL14	3068	0.047	0.29	YES
27	RPS25	RPS25	RPS25	3127	0.045	0.3	YES
28	FAU	FAU	FAU	3152	0.044	0.31	YES
29	RPSA	RPSA	RPSA	3205	0.044	0.32	YES
30	RPL8	RPL8	RPL8	3241	0.043	0.33	YES
31	UBA52	UBA52	UBA52	3275	0.042	0.34	YES
32	RPS24	RPS24	RPS24	3290	0.042	0.35	YES
33	RPL13	RPL13	RPL13	3305	0.042	0.36	YES
34	RPS21	RPS21	RPS21	3336	0.041	0.37	YES
35	RPL28	RPL28	RPL28	3408	0.04	0.38	YES
36	RPL4	RPL4	RPL4	3483	0.038	0.38	YES
37	RPS26	RPS26	RPS26	3600	0.036	0.39	YES
38	RPS18	RPS18	RPS18	3602	0.036	0.4	YES
39	RPL26	RPL26	RPL26	3615	0.036	0.41	YES
40	RPS5	RPS5	RPS5	3719	0.034	0.41	YES
41	RPL7A	RPL7A	RPL7A	3729	0.034	0.42	YES
42	RPS15A	RPS15A	RPS15A	3741	0.033	0.43	YES
43	RPS17	RPS17	RPS17	3759	0.033	0.44	YES
44	RPL37A	RPL37A	RPL37A	3787	0.033	0.44	YES
45	RPL32	RPL32	RPL32	3823	0.032	0.45	YES
46	RPL3L	RPL3L	RPL3L	3839	0.032	0.46	YES
47	RPS9	RPS9	RPS9	3843	0.032	0.47	YES
48	RPL12	RPL12	RPL12	3851	0.032	0.48	YES
49	RPL23A	RPL23A	RPL23A	3867	0.031	0.48	YES
50	RPS8	RPS8	RPS8	3894	0.031	0.49	YES
51	RPL6	RPL6	RPL6	3895	0.031	0.5	YES
52	RPS6	RPS6	RPS6	3916	0.03	0.51	YES
53	RPL5	RPL5	RPL5	3929	0.03	0.52	YES
54	RPL7	RPL7	RPL7	3937	0.03	0.52	YES
55	RPL37	RPL37	RPL37	3948	0.03	0.53	YES
56	RPL24	RPL24	RPL24	4023	0.028	0.54	YES
57	RPS7	RPS7	RPS7	4087	0.027	0.54	YES
58	RPS23	RPS23	RPS23	4103	0.027	0.55	YES
59	RPL17	RPL17	RPL17	4122	0.027	0.55	YES
60	RPL30	RPL30	RPL30	4198	0.026	0.56	YES
61	RPS20	RPS20	RPS20	4242	0.025	0.56	YES
62	RPS27A	RPS27A	RPS27A	4244	0.025	0.57	YES
63	RPL19	RPL19	RPL19	4285	0.024	0.57	YES
64	RPL13A	RPL13A	RPL13A	4302	0.024	0.58	YES
65	RPS4X	RPS4X	RPS4X	4303	0.024	0.58	YES
66	RPL10A	RPL10A	RPL10A	4340	0.023	0.59	YES
67	RPS3A	RPS3A	RPS3A	4366	0.022	0.59	YES
68	RPL31	RPL31	RPL31	4430	0.021	0.6	YES
69	RPS19	RPS19	RPS19	4468	0.021	0.6	YES
70	RPL22	RPL22	RPL22	4519	0.02	0.6	YES
71	RPL10	RPL10	RPL10	4531	0.02	0.61	YES
72	RPL23	RPL23	RPL23	4607	0.018	0.61	YES
73	RPS11	RPS11	RPS11	4759	0.016	0.6	YES
74	RSL24D1	RSL24D1	RSL24D1	4796	0.016	0.61	YES
75	RPLP0	RPLP0	RPLP0	4835	0.015	0.61	YES
76	RPLP1	RPLP1	RPLP1	5277	0.0074	0.59	NO
77	RPL3	RPL3	RPL3	5375	0.0059	0.58	NO
78	RPS28	RPS28	RPS28	5537	0.0034	0.58	NO
79	RPL41	RPL41	RPL41	5808	-0.00081	0.56	NO
80	RPL15	RPL15	RPL15	6554	-0.012	0.52	NO
81	RPS27L	RPS27L	RPS27L	6664	-0.013	0.52	NO
82	RPL35A	RPL35A	RPL35A	6830	-0.016	0.52	NO
83	RPS27	RPS27	RPS27	8072	-0.035	0.46	NO
84	RPS4Y1	RPS4Y1	RPS4Y1	12636	-0.14	0.25	NO
85	RPL21	RPL21	RPL21	15213	-0.23	0.17	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: BIOCARTA PYK2 PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PYK2 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 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	WARS	WARS	WARS	1138	0.13	0.017	YES
2	RARS	RARS	RARS	1598	0.098	0.05	YES
3	GARS	GARS	GARS	2141	0.074	0.064	YES
4	FARS2	FARS2	FARS2	2267	0.069	0.098	YES
5	SARS	SARS	SARS	2272	0.069	0.14	YES
6	HARS	HARS	HARS	2471	0.063	0.16	YES
7	CARS2	CARS2	CARS2	2568	0.06	0.19	YES
8	VARS	VARS	VARS	2642	0.057	0.22	YES
9	KARS	KARS	KARS	2710	0.056	0.25	YES
10	YARS	YARS	YARS	2721	0.055	0.28	YES
11	FARSB	FARSB	FARSB	3095	0.046	0.29	YES
12	CARS	CARS	CARS	3861	0.031	0.27	YES
13	TARS	TARS	TARS	4128	0.027	0.27	YES
14	YARS2	YARS2	YARS2	4532	0.02	0.26	YES
15	FARSA	FARSA	FARSA	4795	0.016	0.25	YES
16	QARS	QARS	QARS	4918	0.014	0.26	YES
17	HARS2	HARS2	HARS2	5275	0.0074	0.24	YES
18	TARSL2	TARSL2	TARSL2	5346	0.0064	0.24	YES
19	SARS2	SARS2	SARS2	5638	0.0019	0.22	YES
20	DARS	DARS	DARS	6345	-0.0086	0.19	YES
21	LARS2	LARS2	LARS2	6473	-0.01	0.19	YES
22	NARS2	NARS2	NARS2	6550	-0.012	0.19	YES
23	MARS	MARS	MARS	6821	-0.016	0.19	YES
24	EARS2	EARS2	EARS2	6851	-0.016	0.2	YES
25	IARS2	IARS2	IARS2	6904	-0.017	0.2	YES
26	NARS	NARS	NARS	6928	-0.017	0.21	YES
27	EPRS	EPRS	EPRS	7039	-0.019	0.22	YES
28	RARS2	RARS2	RARS2	7073	-0.02	0.23	YES
29	IARS	IARS	IARS	7219	-0.022	0.23	YES
30	MTFMT	MTFMT	MTFMT	7302	-0.023	0.24	YES
31	LARS	LARS	LARS	7523	-0.026	0.24	YES
32	WARS2	WARS2	WARS2	7756	-0.03	0.25	YES
33	AARS2	AARS2	AARS2	8380	-0.04	0.24	YES
34	VARS2	VARS2	VARS2	8470	-0.041	0.26	YES
35	AARS	AARS	AARS	8787	-0.047	0.27	YES
36	DARS2	DARS2	DARS2	9110	-0.053	0.28	YES
37	PSTK	PSTK	PSTK	10217	-0.074	0.26	YES
38	SEPSECS	SEPSECS	SEPSECS	10868	-0.087	0.28	YES
39	PARS2	PARS2	PARS2	11445	-0.1	0.31	YES
40	MARS2	MARS2	MARS2	11996	-0.12	0.35	YES

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: BIOCARTA IL1R PATHWAY.

Figure S48. 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 PYRIMIDINE METABOLISM

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	HSPA2	HSPA2	HSPA2	2097	0.076	-0.092	YES
2	EIF4A3	EIF4A3	EIF4A3	2244	0.07	-0.078	YES
3	CWC15	CWC15	CWC15	3077	0.047	-0.11	YES
4	CCDC12	CCDC12	CCDC12	3134	0.045	-0.098	YES
5	HSPA8	HSPA8	HSPA8	3166	0.044	-0.086	YES
6	SNRPB2	SNRPB2	SNRPB2	3183	0.044	-0.074	YES
7	CTNNBL1	CTNNBL1	CTNNBL1	3203	0.044	-0.061	YES
8	DHX38	DHX38	DHX38	3328	0.041	-0.055	YES
9	SF3B5	SF3B5	SF3B5	3329	0.041	-0.042	YES
10	PLRG1	PLRG1	PLRG1	3541	0.037	-0.043	YES
11	PPIL1	PPIL1	PPIL1	3618	0.036	-0.036	YES
12	SNRPA1	SNRPA1	SNRPA1	3665	0.034	-0.028	YES
13	SFRS5	SFRS5	SFRS5	3745	0.033	-0.022	YES
14	SNRPD1	SNRPD1	SNRPD1	3819	0.032	-0.016	YES
15	PUF60	PUF60	PUF60	4003	0.029	-0.017	YES
16	SNRPC	SNRPC	SNRPC	4097	0.027	-0.014	YES
17	PRPF31	PRPF31	PRPF31	4134	0.026	-0.0077	YES
18	SNRPF	SNRPF	SNRPF	4300	0.024	-0.0094	YES
19	TRA2A	TRA2A	TRA2A	4395	0.022	-0.0078	YES
20	PPIE	PPIE	PPIE	4416	0.022	-0.0023	YES
21	SF3B14	SF3B14	SF3B14	4527	0.02	-0.0022	YES
22	SNRPD2	SNRPD2	SNRPD2	4536	0.02	0.0034	YES
23	ZMAT2	ZMAT2	ZMAT2	4610	0.018	0.0051	YES
24	AQR	AQR	AQR	4630	0.018	0.0097	YES
25	SNRPB	SNRPB	SNRPB	4678	0.018	0.013	YES
26	PCBP1	PCBP1	PCBP1	4680	0.018	0.018	YES
27	DHX15	DHX15	DHX15	4682	0.018	0.023	YES
28	LSM7	LSM7	LSM7	4733	0.017	0.026	YES
29	SNRPD3	SNRPD3	SNRPD3	4737	0.017	0.031	YES
30	LSM5	LSM5	LSM5	4911	0.014	0.025	YES
31	BUD31	BUD31	BUD31	4939	0.013	0.028	YES
32	PPIH	PPIH	PPIH	4994	0.012	0.029	YES
33	HNRNPC	HNRNPC	HNRNPC	5068	0.011	0.028	YES
34	SFRS2B	SFRS2B	SFRS2B	5093	0.01	0.03	YES
35	SNW1	SNW1	SNW1	5121	0.0099	0.032	YES
36	SNRNP70	SNRNP70	SNRNP70	5137	0.0097	0.034	YES
37	EFTUD2	EFTUD2	EFTUD2	5158	0.0093	0.036	YES
38	MAGOH	MAGOH	MAGOH	5170	0.0091	0.038	YES
39	SMNDC1	SMNDC1	SMNDC1	5251	0.0078	0.036	YES
40	SNRPG	SNRPG	SNRPG	5271	0.0075	0.037	YES
41	SART1	SART1	SART1	5361	0.0061	0.034	YES
42	PRPF6	PRPF6	PRPF6	5379	0.0058	0.035	YES
43	PRPF38A	PRPF38A	PRPF38A	5423	0.0052	0.034	YES
44	SF3A2	SF3A2	SF3A2	5452	0.0048	0.034	YES
45	RBM22	RBM22	RBM22	5507	0.0038	0.032	YES
46	TXNL4A	TXNL4A	TXNL4A	5510	0.0038	0.033	YES
47	LSM3	LSM3	LSM3	5568	0.0029	0.031	YES
48	PQBP1	PQBP1	PQBP1	5592	0.0027	0.031	YES
49	PRPF19	PRPF19	PRPF19	5657	0.0017	0.028	YES
50	BAT1	BAT1	BAT1	5783	-0.00032	0.021	YES
51	XAB2	XAB2	XAB2	5805	-0.00074	0.02	YES
52	SNRPA	SNRPA	SNRPA	5811	-0.00083	0.02	YES
53	SFRS1	SFRS1	SFRS1	5916	-0.0024	0.015	YES
54	RBM25	RBM25	RBM25	6006	-0.004	0.011	YES
55	HNRNPM	HNRNPM	HNRNPM	6063	-0.0047	0.0097	YES
56	PRPF40B	PRPF40B	PRPF40B	6091	-0.0052	0.0098	YES
57	HNRNPK	HNRNPK	HNRNPK	6102	-0.0054	0.011	YES
58	SYF2	SYF2	SYF2	6144	-0.006	0.011	YES
59	U2AF2	U2AF2	U2AF2	6171	-0.0064	0.011	YES
60	THOC4	THOC4	THOC4	6186	-0.0065	0.012	YES
61	SF3B2	SF3B2	SF3B2	6192	-0.0066	0.014	YES
62	NHP2L1	NHP2L1	NHP2L1	6250	-0.0073	0.013	YES
63	SF3B3	SF3B3	SF3B3	6258	-0.0075	0.015	YES
64	NCBP1	NCBP1	NCBP1	6277	-0.0077	0.017	YES
65	SFRS3	SFRS3	SFRS3	6339	-0.0085	0.016	YES
66	HNRNPA1	HNRNPA1	HNRNPA1	6347	-0.0086	0.018	YES
67	RBM17	RBM17	RBM17	6378	-0.009	0.019	YES
68	SFRS9	SFRS9	SFRS9	6386	-0.0091	0.022	YES
69	U2AF1	U2AF1	U2AF1	6400	-0.0093	0.024	YES
70	SF3A3	SF3A3	SF3A3	6496	-0.011	0.022	YES
71	DHX16	DHX16	DHX16	6516	-0.011	0.024	YES
72	TCERG1	TCERG1	TCERG1	6520	-0.011	0.027	YES
73	SLU7	SLU7	SLU7	6540	-0.011	0.03	YES
74	SFRS4	SFRS4	SFRS4	6544	-0.011	0.033	YES
75	DDX23	DDX23	DDX23	6645	-0.013	0.032	YES
76	SFRS2	SFRS2	SFRS2	6653	-0.013	0.035	YES
77	RBM8A	RBM8A	RBM8A	6716	-0.014	0.036	YES
78	PRPF40A	PRPF40A	PRPF40A	6765	-0.015	0.038	YES
79	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6841	-0.016	0.039	YES
80	SFRS6	SFRS6	SFRS6	6873	-0.016	0.042	YES
81	ACIN1	ACIN1	ACIN1	6878	-0.016	0.047	YES
82	DHX8	DHX8	DHX8	6986	-0.018	0.047	YES
83	CRNKL1	CRNKL1	CRNKL1	7011	-0.019	0.051	YES
84	DDX5	DDX5	DDX5	7071	-0.02	0.054	YES
85	SNRNP40	SNRNP40	SNRNP40	7161	-0.021	0.056	YES
86	SF3B4	SF3B4	SF3B4	7205	-0.022	0.06	YES
87	SNRPE	SNRPE	SNRPE	7231	-0.022	0.065	YES
88	LSM4	LSM4	LSM4	7258	-0.022	0.071	YES
89	LSM2	LSM2	LSM2	7329	-0.024	0.074	YES
90	PHF5A	PHF5A	PHF5A	7436	-0.025	0.076	YES
91	PRPF18	PRPF18	PRPF18	7470	-0.026	0.082	YES
92	LSM6	LSM6	LSM6	7491	-0.026	0.089	YES
93	PRPF4	PRPF4	PRPF4	7529	-0.026	0.095	YES
94	HNRNPU	HNRNPU	HNRNPU	7691	-0.029	0.096	YES
95	BCAS2	BCAS2	BCAS2	7702	-0.029	0.1	YES
96	THOC1	THOC1	THOC1	7789	-0.03	0.11	YES
97	DDX46	DDX46	DDX46	7817	-0.031	0.12	YES
98	SFRS7	SFRS7	SFRS7	7928	-0.033	0.12	YES
99	PRPF38B	PRPF38B	PRPF38B	7967	-0.034	0.13	YES
100	CDC5L	CDC5L	CDC5L	7989	-0.034	0.14	YES
101	SFRS13A	SFRS13A	SFRS13A	8164	-0.037	0.14	YES
102	DDX42	DDX42	DDX42	8176	-0.037	0.15	YES
103	HNRNPA3	HNRNPA3	HNRNPA3	8257	-0.038	0.16	YES
104	HSPA6	HSPA6	HSPA6	8337	-0.039	0.17	YES
105	MAGOHB	MAGOHB	MAGOHB	8349	-0.039	0.18	YES
106	PRPF8	PRPF8	PRPF8	8432	-0.04	0.19	YES
107	SF3B1	SF3B1	SF3B1	8477	-0.041	0.2	YES
108	PRPF3	PRPF3	PRPF3	8482	-0.041	0.21	YES
109	CDC40	CDC40	CDC40	8551	-0.042	0.22	YES
110	ISY1	ISY1	ISY1	8560	-0.043	0.23	YES
111	SNRNP27	SNRNP27	SNRNP27	8621	-0.044	0.24	YES
112	SR140	SR140	SR140	8626	-0.044	0.25	YES
113	HSPA1B	HSPA1B	HSPA1B	8738	-0.046	0.26	YES
114	CHERP	CHERP	CHERP	8742	-0.046	0.28	YES
115	TRA2B	TRA2B	TRA2B	8743	-0.046	0.29	YES
116	THOC2	THOC2	THOC2	8769	-0.046	0.3	YES
117	SF3A1	SF3A1	SF3A1	8773	-0.047	0.32	YES
118	NAA38	NAA38	NAA38	9038	-0.051	0.32	YES
119	RBMX	RBMX	RBMX	9062	-0.052	0.33	YES
120	SNRNP200	SNRNP200	SNRNP200	9180	-0.054	0.34	YES
121	THOC3	THOC3	THOC3	9405	-0.058	0.35	YES
122	WBP11	WBP11	WBP11	9915	-0.067	0.34	YES
123	HSPA1A	HSPA1A	HSPA1A	10033	-0.07	0.36	YES
124	USP39	USP39	USP39	10601	-0.082	0.35	NO
125	HSPA1L	HSPA1L	HSPA1L	15344	-0.24	0.16	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: KEGG PYRIMIDINE METABOLISM.

Figure S50. 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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

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	IFNE	IFNE	IFNE	261	0.35	0.055	YES
2	IFNK	IFNK	IFNK	371	0.29	0.11	YES
3	ISG15	ISG15	ISG15	488	0.25	0.15	YES
4	NLRX1	NLRX1	NLRX1	599	0.22	0.19	YES
5	IRF7	IRF7	IRF7	711	0.19	0.22	YES
6	IFNA13	IFNA13	IFNA13	806	0.18	0.25	YES
7	DDX58	DDX58	DDX58	890	0.16	0.28	YES
8	IL8	IL8	IL8	971	0.15	0.3	YES
9	IFNA1	IFNA1	IFNA1	975	0.15	0.33	YES
10	IFIH1	IFIH1	IFIH1	1024	0.15	0.36	YES
11	MAPK13	MAPK13	MAPK13	1233	0.13	0.37	YES
12	CXCL10	CXCL10	CXCL10	1283	0.12	0.39	YES
13	TRADD	TRADD	TRADD	1625	0.097	0.39	YES
14	CASP10	CASP10	CASP10	1802	0.087	0.4	YES
15	DHX58	DHX58	DHX58	2646	0.057	0.37	NO
16	MAPK14	MAPK14	MAPK14	2929	0.05	0.36	NO
17	TNF	TNF	TNF	2951	0.049	0.37	NO
18	DDX3X	DDX3X	DDX3X	3206	0.044	0.36	NO
19	ATG12	ATG12	ATG12	3392	0.04	0.36	NO
20	CYLD	CYLD	CYLD	3558	0.036	0.36	NO
21	FADD	FADD	FADD	3795	0.032	0.35	NO
22	RELA	RELA	RELA	4106	0.027	0.34	NO
23	CASP8	CASP8	CASP8	4141	0.026	0.34	NO
24	TRIM25	TRIM25	TRIM25	4322	0.023	0.34	NO
25	IRF3	IRF3	IRF3	4414	0.022	0.34	NO
26	NFKBIB	NFKBIB	NFKBIB	4421	0.021	0.34	NO
27	AZI2	AZI2	AZI2	4469	0.021	0.34	NO
28	RIPK1	RIPK1	RIPK1	5029	0.012	0.32	NO
29	IFNB1	IFNB1	IFNB1	5165	0.0092	0.31	NO
30	MAPK11	MAPK11	MAPK11	5322	0.0068	0.3	NO
31	NFKBIA	NFKBIA	NFKBIA	5419	0.0052	0.3	NO
32	NFKB1	NFKB1	NFKB1	5544	0.0032	0.29	NO
33	MAP3K7	MAP3K7	MAP3K7	5861	-0.0015	0.28	NO
34	IKBKG	IKBKG	IKBKG	5923	-0.0025	0.27	NO
35	CHUK	CHUK	CHUK	6098	-0.0053	0.26	NO
36	PIN1	PIN1	PIN1	6172	-0.0064	0.26	NO
37	TMEM173	TMEM173	TMEM173	6311	-0.0082	0.26	NO
38	TANK	TANK	TANK	6314	-0.0083	0.26	NO
39	SIKE1	SIKE1	SIKE1	6374	-0.0089	0.26	NO
40	TRAF3	TRAF3	TRAF3	6810	-0.015	0.24	NO
41	MAP3K1	MAP3K1	MAP3K1	6843	-0.016	0.24	NO
42	OTUD5	OTUD5	OTUD5	6947	-0.018	0.24	NO
43	ATG5	ATG5	ATG5	7296	-0.023	0.22	NO
44	DAK	DAK	DAK	7677	-0.029	0.2	NO
45	MAPK9	MAPK9	MAPK9	7940	-0.033	0.2	NO
46	TRAF6	TRAF6	TRAF6	8104	-0.036	0.2	NO
47	MAVS	MAVS	MAVS	8501	-0.042	0.18	NO
48	TBK1	TBK1	TBK1	8519	-0.042	0.19	NO
49	IKBKE	IKBKE	IKBKE	8737	-0.046	0.19	NO
50	TRAF2	TRAF2	TRAF2	9324	-0.056	0.17	NO
51	IKBKB	IKBKB	IKBKB	9933	-0.068	0.15	NO
52	IL12B	IL12B	IL12B	10880	-0.087	0.11	NO
53	TBKBP1	TBKBP1	TBKBP1	11247	-0.096	0.11	NO
54	MAPK8	MAPK8	MAPK8	13037	-0.15	0.042	NO
55	MAPK12	MAPK12	MAPK12	13833	-0.18	0.033	NO
56	DDX3Y	DDX3Y	DDX3Y	13869	-0.18	0.066	NO
57	MAPK10	MAPK10	MAPK10	15010	-0.22	0.048	NO
58	RNF125	RNF125	RNF125	15876	-0.27	0.054	NO
59	IL12A	IL12A	IL12A	17596	-0.41	0.042	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: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S52. 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 ETHER LIPID METABOLISM

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	CARD18	CARD18	CARD18	47	0.57	0.084	YES
2	MEFV	MEFV	MEFV	95	0.49	0.16	YES
3	NOD2	NOD2	NOD2	248	0.36	0.2	YES
4	IL1B	IL1B	IL1B	320	0.31	0.25	YES
5	IL18	IL18	IL18	334	0.31	0.29	YES
6	CARD6	CARD6	CARD6	518	0.24	0.32	YES
7	CASP1	CASP1	CASP1	698	0.19	0.34	YES
8	PYCARD	PYCARD	PYCARD	720	0.19	0.37	YES
9	CASP5	CASP5	CASP5	730	0.19	0.4	YES
10	CXCL1	CXCL1	CXCL1	744	0.19	0.42	YES
11	IL8	IL8	IL8	971	0.15	0.44	YES
12	MAPK13	MAPK13	MAPK13	1233	0.13	0.44	YES
13	SUGT1	SUGT1	SUGT1	1305	0.12	0.46	YES
14	MAPK3	MAPK3	MAPK3	1411	0.11	0.47	YES
15	CXCL2	CXCL2	CXCL2	2131	0.074	0.44	NO
16	CCL7	CCL7	CCL7	2686	0.056	0.42	NO
17	NLRP1	NLRP1	NLRP1	2839	0.052	0.42	NO
18	MAPK14	MAPK14	MAPK14	2929	0.05	0.42	NO
19	CCL5	CCL5	CCL5	2944	0.05	0.43	NO
20	TNF	TNF	TNF	2951	0.049	0.43	NO
21	TRIP6	TRIP6	TRIP6	3115	0.046	0.43	NO
22	RIPK2	RIPK2	RIPK2	3417	0.039	0.42	NO
23	CCL8	CCL8	CCL8	3699	0.034	0.41	NO
24	RELA	RELA	RELA	4106	0.027	0.39	NO
25	TAB2	TAB2	TAB2	4107	0.027	0.4	NO
26	CASP8	CASP8	CASP8	4141	0.026	0.4	NO
27	NLRP3	NLRP3	NLRP3	4299	0.024	0.39	NO
28	NOD1	NOD1	NOD1	4362	0.022	0.39	NO
29	NFKBIB	NFKBIB	NFKBIB	4421	0.021	0.4	NO
30	MAPK11	MAPK11	MAPK11	5322	0.0068	0.35	NO
31	NFKBIA	NFKBIA	NFKBIA	5419	0.0052	0.34	NO
32	NFKB1	NFKB1	NFKB1	5544	0.0032	0.34	NO
33	MAP3K7	MAP3K7	MAP3K7	5861	-0.0015	0.32	NO
34	TNFAIP3	TNFAIP3	TNFAIP3	5887	-0.0019	0.32	NO
35	IKBKG	IKBKG	IKBKG	5923	-0.0025	0.32	NO
36	HSP90AA1	HSP90AA1	HSP90AA1	6046	-0.0046	0.31	NO
37	BIRC2	BIRC2	BIRC2	6080	-0.005	0.31	NO
38	CHUK	CHUK	CHUK	6098	-0.0053	0.31	NO
39	TAB3	TAB3	TAB3	6315	-0.0083	0.3	NO
40	MAPK1	MAPK1	MAPK1	6457	-0.01	0.29	NO
41	CCL13	CCL13	CCL13	6614	-0.012	0.29	NO
42	HSP90B1	HSP90B1	HSP90B1	7363	-0.024	0.25	NO
43	XIAP	XIAP	XIAP	7743	-0.03	0.23	NO
44	MAPK9	MAPK9	MAPK9	7940	-0.033	0.23	NO
45	IL6	IL6	IL6	7998	-0.034	0.23	NO
46	TRAF6	TRAF6	TRAF6	8104	-0.036	0.23	NO
47	CCL11	CCL11	CCL11	9597	-0.061	0.16	NO
48	ERBB2IP	ERBB2IP	ERBB2IP	9830	-0.066	0.15	NO
49	IKBKB	IKBKB	IKBKB	9933	-0.068	0.16	NO
50	TAB1	TAB1	TAB1	9935	-0.068	0.17	NO
51	PSTPIP1	PSTPIP1	PSTPIP1	10323	-0.076	0.16	NO
52	PYDC1	PYDC1	PYDC1	12956	-0.15	0.038	NO
53	CCL2	CCL2	CCL2	13025	-0.15	0.056	NO
54	MAPK8	MAPK8	MAPK8	13037	-0.15	0.079	NO
55	CARD8	CARD8	CARD8	13333	-0.16	0.087	NO
56	BIRC3	BIRC3	BIRC3	13459	-0.16	0.1	NO
57	MAPK12	MAPK12	MAPK12	13833	-0.18	0.11	NO
58	CARD9	CARD9	CARD9	14318	-0.19	0.11	NO
59	NLRC4	NLRC4	NLRC4	14422	-0.2	0.14	NO
60	MAPK10	MAPK10	MAPK10	15010	-0.22	0.14	NO
61	NAIP	NAIP	NAIP	15935	-0.27	0.13	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: KEGG ETHER LIPID METABOLISM.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ETHER LIPID 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 AMINOACYL TRNA BIOSYNTHESIS

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	VEGFC	VEGFC	VEGFC	274	0.34	0.067	YES
2	MMP1	MMP1	MMP1	580	0.22	0.11	YES
3	TYMP	TYMP	TYMP	708	0.19	0.15	YES
4	PGF	PGF	PGF	771	0.18	0.19	YES
5	IL8	IL8	IL8	971	0.15	0.21	YES
6	CDKN1A	CDKN1A	CDKN1A	987	0.15	0.25	YES
7	HRAS	HRAS	HRAS	1050	0.14	0.28	YES
8	MAPK3	MAPK3	MAPK3	1411	0.11	0.29	YES
9	CDH1	CDH1	CDH1	1799	0.087	0.29	YES
10	FGFR3	FGFR3	FGFR3	1852	0.085	0.31	YES
11	MYC	MYC	MYC	2028	0.078	0.32	YES
12	DAPK3	DAPK3	DAPK3	2664	0.057	0.3	NO
13	NRAS	NRAS	NRAS	3390	0.04	0.27	NO
14	RB1	RB1	RB1	3534	0.037	0.27	NO
15	MAP2K2	MAP2K2	MAP2K2	4008	0.029	0.25	NO
16	VEGFA	VEGFA	VEGFA	4355	0.023	0.24	NO
17	EGFR	EGFR	EGFR	4701	0.017	0.22	NO
18	MAP2K1	MAP2K1	MAP2K1	5031	0.012	0.21	NO
19	ERBB2	ERBB2	ERBB2	5291	0.0073	0.2	NO
20	THBS1	THBS1	THBS1	5679	0.0014	0.18	NO
21	RASSF1	RASSF1	RASSF1	5735	0.00049	0.17	NO
22	MAPK1	MAPK1	MAPK1	6457	-0.01	0.14	NO
23	VEGFB	VEGFB	VEGFB	6522	-0.011	0.13	NO
24	CCND1	CCND1	CCND1	7375	-0.024	0.093	NO
25	RAF1	RAF1	RAF1	7446	-0.025	0.096	NO
26	ARAF	ARAF	ARAF	7927	-0.033	0.078	NO
27	MMP9	MMP9	MMP9	8616	-0.043	0.051	NO
28	BRAF	BRAF	BRAF	8631	-0.044	0.061	NO
29	KRAS	KRAS	KRAS	8651	-0.044	0.07	NO
30	E2F2	E2F2	E2F2	9564	-0.06	0.036	NO
31	E2F3	E2F3	E2F3	9790	-0.065	0.039	NO
32	MDM2	MDM2	MDM2	9798	-0.065	0.055	NO
33	DAPK1	DAPK1	DAPK1	10195	-0.073	0.051	NO
34	CDK4	CDK4	CDK4	10389	-0.077	0.06	NO
35	MMP2	MMP2	MMP2	10530	-0.08	0.072	NO
36	DAPK2	DAPK2	DAPK2	11750	-0.11	0.032	NO
37	RPS6KA5	RPS6KA5	RPS6KA5	12198	-0.12	0.037	NO
38	TP53	TP53	TP53	13719	-0.17	-0.0033	NO
39	CDKN2A	CDKN2A	CDKN2A	13977	-0.18	0.027	NO
40	EGF	EGF	EGF	17392	-0.39	-0.064	NO
41	FIGF	FIGF	FIGF	17999	-0.47	0.02	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: KEGG AMINOACYL TRNA BIOSYNTHESIS.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS, 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 RIBOSOME

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	CDKN1A	CDKN1A	CDKN1A	987	0.15	0.042	YES
2	HRAS	HRAS	HRAS	1050	0.14	0.13	YES
3	CCNE1	CCNE1	CCNE1	1219	0.13	0.2	YES
4	MAPK3	MAPK3	MAPK3	1411	0.11	0.26	YES
5	CDK6	CDK6	CDK6	1884	0.084	0.28	YES
6	RAC1	RAC1	RAC1	2855	0.052	0.26	NO
7	RB1	RB1	RB1	3534	0.037	0.25	NO
8	TFDP1	TFDP1	TFDP1	3646	0.035	0.27	NO
9	RELA	RELA	RELA	4106	0.027	0.26	NO
10	RHOA	RHOA	RHOA	4687	0.017	0.24	NO
11	NFKBIA	NFKBIA	NFKBIA	5419	0.0052	0.2	NO
12	NFKB1	NFKB1	NFKB1	5544	0.0032	0.2	NO
13	PAK1	PAK1	PAK1	5584	0.0028	0.2	NO
14	IKBKG	IKBKG	IKBKG	5923	-0.0025	0.18	NO
15	CHUK	CHUK	CHUK	6098	-0.0053	0.17	NO
16	MAPK1	MAPK1	MAPK1	6457	-0.01	0.16	NO
17	AKT1	AKT1	AKT1	7134	-0.02	0.14	NO
18	CCND1	CCND1	CCND1	7375	-0.024	0.14	NO
19	RAF1	RAF1	RAF1	7446	-0.025	0.15	NO
20	IKBKB	IKBKB	IKBKB	9933	-0.068	0.056	NO
21	CDK4	CDK4	CDK4	10389	-0.077	0.08	NO
22	CDK2	CDK2	CDK2	11468	-0.1	0.085	NO
23	PIK3CA	PIK3CA	PIK3CA	12036	-0.12	0.13	NO
24	CDKN1B	CDKN1B	CDKN1B	12302	-0.12	0.19	NO
25	PIK3R1	PIK3R1	PIK3R1	14952	-0.22	0.19	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: KEGG RIBOSOME.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIBOSOME, 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 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	STX11	STX11	STX11	799	0.18	0.032	YES
2	STX19	STX19	STX19	1357	0.12	0.051	YES
3	VAMP8	VAMP8	VAMP8	1786	0.088	0.065	YES
4	STX3	STX3	STX3	1935	0.082	0.091	YES
5	VAMP3	VAMP3	VAMP3	2084	0.076	0.12	YES
6	VTI1B	VTI1B	VTI1B	2109	0.075	0.15	YES
7	YKT6	YKT6	YKT6	2176	0.073	0.17	YES
8	STX4	STX4	STX4	2516	0.061	0.18	YES
9	STX10	STX10	STX10	2559	0.06	0.2	YES
10	STX8	STX8	STX8	2874	0.051	0.21	YES
11	STX6	STX6	STX6	3187	0.044	0.21	YES
12	BNIP1	BNIP1	BNIP1	3359	0.041	0.22	YES
13	STX17	STX17	STX17	3386	0.04	0.23	YES
14	VTI1A	VTI1A	VTI1A	3405	0.04	0.25	YES
15	STX7	STX7	STX7	3528	0.037	0.26	YES
16	STX12	STX12	STX12	3587	0.036	0.27	YES
17	GOSR2	GOSR2	GOSR2	4102	0.027	0.25	NO
18	STX5	STX5	STX5	4269	0.024	0.26	NO
19	STX1A	STX1A	STX1A	5359	0.0062	0.2	NO
20	BET1L	BET1L	BET1L	5493	0.004	0.19	NO
21	STX16	STX16	STX16	5936	-0.0028	0.17	NO
22	STX18	STX18	STX18	6018	-0.0042	0.17	NO
23	VAMP7	VAMP7	VAMP7	6857	-0.016	0.13	NO
24	VAMP2	VAMP2	VAMP2	7309	-0.023	0.11	NO
25	GOSR1	GOSR1	GOSR1	7331	-0.024	0.12	NO
26	VAMP4	VAMP4	VAMP4	7345	-0.024	0.13	NO
27	USE1	USE1	USE1	7988	-0.034	0.11	NO
28	SEC22B	SEC22B	SEC22B	8019	-0.034	0.12	NO
29	SNAP23	SNAP23	SNAP23	8277	-0.038	0.13	NO
30	BET1	BET1	BET1	8514	-0.042	0.13	NO
31	STX2	STX2	STX2	8764	-0.046	0.14	NO
32	STX1B	STX1B	STX1B	10203	-0.073	0.09	NO
33	SNAP47	SNAP47	SNAP47	10865	-0.087	0.091	NO
34	VAMP5	VAMP5	VAMP5	10938	-0.089	0.12	NO
35	SNAP25	SNAP25	SNAP25	13765	-0.17	0.044	NO
36	TSNARE1	TSNARE1	TSNARE1	13909	-0.18	0.11	NO
37	VAMP1	VAMP1	VAMP1	16436	-0.31	0.1	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: KEGG RNA POLYMERASE.

Figure S60. 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

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 = HNSC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = HNSC-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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