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

Esophageal Carcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in ESCA-TP. Broad Institute of MIT and Harvard. doi:10.7908/C18051MX

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 ESCA-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: 194
Number of samples: 184
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 ] 85
pheno.type: 2 - 3 :[ clus2 ] 68
pheno.type: 3 - 3 :[ clus3 ] 31

For the expression subtypes of 23680 genes in 185 samples, GSEA found enriched gene sets in each cluster using 184 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA DEATH PATHWAY, BIOCARTA PPARA PATHWAY, BIOCARTA RHO PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG HISTIDINE METABOLISM

And common core enriched genes are PRKACG, PRKCA, NOS2, CFTR, KCNQ1, KDELR3, MUC2, PRKCG, SLC12A2, APOA1

clus2

Top enriched gene sets are BIOCARTA CARM ER PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA GSK3 PATHWAY, BIOCARTA INTEGRIN PATHWAY, BIOCARTA MYOSIN PATHWAY, KEGG RNA DEGRADATION, KEGG CELL CYCLE, KEGG OOCYTE MEIOSIS, KEGG P53 SIGNALING PATHWAY, KEGG MTOR SIGNALING PATHWAY

And common core enriched genes are CALML3, CALML5, CAMK2A, CAMK2B, NGF, NGFR, GNGT1, DVL2, FZD1, FZD2

clus3

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA MAPK PATHWAY, BIOCARTA IL1R PATHWAY, KEGG OXIDATIVE PHOSPHORYLATION, KEGG ETHER LIPID METABOLISM, KEGG ARACHIDONIC ACID METABOLISM, KEGG RETINOL METABOLISM, KEGG RIBOSOME, KEGG RNA POLYMERASE

And common core enriched genes are ADAM17, ATP6V0A4, ATP6V0C, ATP6V1B1, ATP6V1D, ATP6V1F, CXCR1, CXCR2, EGFR, HBEGF

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	29	genes.ES.table	0.54	1.5	0.041	0.39	0.78	0.48	0.25	0.36	0.27	0.091
BIOCARTA DEATH PATHWAY	31	genes.ES.table	0.46	1.6	0.071	0.38	0.69	0.61	0.33	0.41	0.22	0.1
BIOCARTA PPARA PATHWAY	55	genes.ES.table	0.54	1.9	0.002	0.14	0.14	0.16	0.095	0.15	0	0.039
BIOCARTA RHO PATHWAY	30	genes.ES.table	0.47	1.8	0.014	0.12	0.25	0.067	0.038	0.064	0	0.033
KEGG GLYCOLYSIS GLUCONEOGENESIS	60	genes.ES.table	0.43	1.5	0.058	0.38	0.83	0.2	0.075	0.18	0.27	0.078
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.5	1.5	0.074	0.36	0.79	0.12	0.041	0.12	0.25	0.078
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.46	1.5	0.077	0.36	0.8	0.34	0.2	0.28	0.25	0.075
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	31	genes.ES.table	0.57	1.7	0.002	0.26	0.46	0.29	0.11	0.26	0	0.065
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.46	1.6	0.066	0.36	0.66	0.49	0.32	0.33	0.19	0.094
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.55	1.5	0.038	0.38	0.79	0.18	0.043	0.17	0.26	0.091

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	CFTR	CFTR	CFTR	80	1.3	0.15	YES
2	PRKCG	PRKCG	PRKCG	297	0.86	0.24	YES
3	PRKACG	PRKACG	PRKACG	397	0.77	0.32	YES
4	MUC2	MUC2	MUC2	415	0.76	0.41	YES
5	KCNQ1	KCNQ1	KCNQ1	635	0.63	0.47	YES
6	SLC12A2	SLC12A2	SLC12A2	1231	0.43	0.49	YES
7	PRKCA	PRKCA	PRKCA	1997	0.31	0.49	YES
8	KDELR3	KDELR3	KDELR3	2117	0.3	0.52	YES
9	TJP2	TJP2	TJP2	3737	0.18	0.47	NO
10	TCIRG1	TCIRG1	TCIRG1	5067	0.12	0.42	NO
11	KDELR2	KDELR2	KDELR2	5080	0.12	0.44	NO
12	PRKCB	PRKCB	PRKCB	5678	0.099	0.42	NO
13	KDELR1	KDELR1	KDELR1	6346	0.081	0.4	NO
14	ATP6V0A2	ATP6V0A2	ATP6V0A2	6681	0.073	0.4	NO
15	ATP6V0E2	ATP6V0E2	ATP6V0E2	6800	0.071	0.4	NO
16	PDIA4	PDIA4	PDIA4	6868	0.07	0.4	NO
17	ATP6V0A1	ATP6V0A1	ATP6V0A1	7717	0.051	0.37	NO
18	ATP6V0B	ATP6V0B	ATP6V0B	7927	0.047	0.37	NO
19	TJP1	TJP1	TJP1	8964	0.03	0.33	NO
20	SEC61A2	SEC61A2	SEC61A2	9024	0.029	0.33	NO
21	ATP6V1C2	ATP6V1C2	ATP6V1C2	9227	0.025	0.32	NO
22	ARF1	ARF1	ARF1	9272	0.024	0.32	NO
23	ATP6AP1	ATP6AP1	ATP6AP1	10275	0.0095	0.28	NO
24	ATP6V1C1	ATP6V1C1	ATP6V1C1	10658	0.0044	0.26	NO
25	SEC61A1	SEC61A1	SEC61A1	11081	-0.0012	0.24	NO
26	SEC61B	SEC61B	SEC61B	11486	-0.0067	0.23	NO
27	ATP6V1B2	ATP6V1B2	ATP6V1B2	12474	-0.02	0.19	NO
28	ACTB	ACTB	ACTB	12526	-0.021	0.19	NO
29	ACTG1	ACTG1	ACTG1	12840	-0.025	0.18	NO
30	SEC61G	SEC61G	SEC61G	12896	-0.026	0.18	NO
31	ATP6V0E1	ATP6V0E1	ATP6V0E1	12922	-0.026	0.18	NO
32	ATP6V0D1	ATP6V0D1	ATP6V0D1	13172	-0.029	0.17	NO
33	PRKACB	PRKACB	PRKACB	13949	-0.041	0.14	NO
34	ADCY9	ADCY9	ADCY9	13976	-0.041	0.15	NO
35	GNAS	GNAS	GNAS	14053	-0.042	0.15	NO
36	ERO1L	ERO1L	ERO1L	14472	-0.049	0.13	NO
37	PLCG2	PLCG2	PLCG2	14761	-0.054	0.13	NO
38	ATP6V1G2	ATP6V1G2	ATP6V1G2	14858	-0.056	0.13	NO
39	ATP6V0C	ATP6V0C	ATP6V0C	15079	-0.059	0.13	NO
40	PLCG1	PLCG1	PLCG1	15217	-0.062	0.13	NO
41	ATP6V1A	ATP6V1A	ATP6V1A	15342	-0.064	0.13	NO
42	ATP6V1G1	ATP6V1G1	ATP6V1G1	15362	-0.064	0.14	NO
43	ATP6V1H	ATP6V1H	ATP6V1H	15654	-0.07	0.13	NO
44	ATP6V1D	ATP6V1D	ATP6V1D	15720	-0.071	0.14	NO
45	PRKACA	PRKACA	PRKACA	15975	-0.076	0.13	NO
46	ATP6V1F	ATP6V1F	ATP6V1F	16351	-0.084	0.13	NO
47	ATP6V1E1	ATP6V1E1	ATP6V1E1	16675	-0.092	0.12	NO
48	ATP6V0D2	ATP6V0D2	ATP6V0D2	18742	-0.16	0.051	NO
49	PRKX	PRKX	PRKX	19250	-0.19	0.05	NO
50	ATP6V0A4	ATP6V0A4	ATP6V0A4	20366	-0.27	0.032	NO
51	ATP6V1E2	ATP6V1E2	ATP6V1E2	20698	-0.31	0.053	NO
52	ATP6V1B1	ATP6V1B1	ATP6V1B1	21174	-0.37	0.074	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 DEATH 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	NR0B2	NR0B2	NR0B2	28	1.6	0.17	YES
2	FABP1	FABP1	FABP1	179	1	0.27	YES
3	PRKACG	PRKACG	PRKACG	397	0.77	0.34	YES
4	NOS2	NOS2	NOS2	574	0.66	0.4	YES
5	APOA1	APOA1	APOA1	718	0.59	0.45	YES
6	PPARGC1A	PPARGC1A	PPARGC1A	1256	0.43	0.47	YES
7	APOA2	APOA2	APOA2	1295	0.42	0.51	YES
8	PRKCA	PRKCA	PRKCA	1997	0.31	0.52	YES
9	PIK3CG	PIK3CG	PIK3CG	2168	0.29	0.54	YES
10	NR1H3	NR1H3	NR1H3	2858	0.23	0.53	NO
11	STAT5A	STAT5A	STAT5A	3621	0.18	0.52	NO
12	MAPK3	MAPK3	MAPK3	5471	0.11	0.44	NO
13	NR2F1	NR2F1	NR2F1	5500	0.11	0.46	NO
14	PRKAR2A	PRKAR2A	PRKAR2A	5537	0.1	0.46	NO
15	PRKCB	PRKCB	PRKCB	5678	0.099	0.47	NO
16	PDGFA	PDGFA	PDGFA	5853	0.094	0.47	NO
17	PPARA	PPARA	PPARA	6532	0.077	0.45	NO
18	NCOR1	NCOR1	NCOR1	6685	0.073	0.45	NO
19	MED1	MED1	MED1	7607	0.054	0.41	NO
20	LPL	LPL	LPL	8009	0.046	0.4	NO
21	STAT5B	STAT5B	STAT5B	8204	0.043	0.4	NO
22	PTGS2	PTGS2	PTGS2	8437	0.038	0.39	NO
23	HSD17B4	HSD17B4	HSD17B4	8490	0.038	0.39	NO
24	PRKAR1B	PRKAR1B	PRKAR1B	9526	0.021	0.35	NO
25	FAT1	FAT1	FAT1	9729	0.018	0.34	NO
26	PIK3R1	PIK3R1	PIK3R1	9941	0.014	0.33	NO
27	NCOA1	NCOA1	NCOA1	10388	0.0081	0.32	NO
28	SP1	SP1	SP1	10538	0.0063	0.31	NO
29	NCOR2	NCOR2	NCOR2	11495	-0.0068	0.27	NO
30	CPT1B	CPT1B	CPT1B	12071	-0.015	0.24	NO
31	HSP90AA1	HSP90AA1	HSP90AA1	12188	-0.016	0.24	NO
32	PRKAR1A	PRKAR1A	PRKAR1A	12244	-0.017	0.24	NO
33	RELA	RELA	RELA	12557	-0.022	0.23	NO
34	SRA1	SRA1	SRA1	12652	-0.023	0.23	NO
35	EP300	EP300	EP300	12761	-0.024	0.22	NO
36	RB1	RB1	RB1	13026	-0.028	0.22	NO
37	EHHADH	EHHADH	EHHADH	13171	-0.029	0.21	NO
38	MRPL11	MRPL11	MRPL11	13351	-0.032	0.21	NO
39	PRKACB	PRKACB	PRKACB	13949	-0.041	0.19	NO
40	CREBBP	CREBBP	CREBBP	14137	-0.044	0.18	NO
41	CITED2	CITED2	CITED2	14559	-0.05	0.17	NO
42	MAPK1	MAPK1	MAPK1	14655	-0.052	0.17	NO
43	JUN	JUN	JUN	16677	-0.092	0.091	NO
44	PRKAR2B	PRKAR2B	PRKAR2B	17105	-0.1	0.083	NO
45	NRIP1	NRIP1	NRIP1	17160	-0.1	0.091	NO
46	TNF	TNF	TNF	17422	-0.11	0.091	NO
47	MYC	MYC	MYC	17466	-0.11	0.1	NO
48	DUT	DUT	DUT	17937	-0.13	0.094	NO
49	NFKBIA	NFKBIA	NFKBIA	18285	-0.14	0.093	NO
50	DUSP1	DUSP1	DUSP1	18537	-0.15	0.098	NO
51	PIK3CA	PIK3CA	PIK3CA	18593	-0.16	0.11	NO
52	HSPA1A	HSPA1A	HSPA1A	18819	-0.17	0.12	NO
53	RXRA	RXRA	RXRA	18977	-0.18	0.13	NO
54	ME1	ME1	ME1	19026	-0.18	0.14	NO
55	CD36	CD36	CD36	19747	-0.22	0.14	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 DEATH PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA DEATH 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 PPARA 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	CREB3L3	CREB3L3	CREB3L3	89	1.3	0.18	YES
2	AQP2	AQP2	AQP2	368	0.8	0.28	YES
3	PRKACG	PRKACG	PRKACG	397	0.77	0.39	YES
4	CREB3L1	CREB3L1	CREB3L1	654	0.62	0.46	YES
5	ADCY6	ADCY6	ADCY6	1605	0.36	0.47	YES
6	AVPR2	AVPR2	AVPR2	2213	0.29	0.48	YES
7	CREB3L4	CREB3L4	CREB3L4	5035	0.12	0.38	NO
8	CREB3	CREB3	CREB3	6344	0.081	0.33	NO
9	NSF	NSF	NSF	6383	0.08	0.34	NO
10	DYNC2LI1	DYNC2LI1	DYNC2LI1	7436	0.057	0.3	NO
11	CREB3L2	CREB3L2	CREB3L2	7781	0.05	0.3	NO
12	RAB5A	RAB5A	RAB5A	8432	0.039	0.27	NO
13	RAB5C	RAB5C	RAB5C	8446	0.038	0.28	NO
14	ARHGDIB	ARHGDIB	ARHGDIB	8556	0.037	0.28	NO
15	RAB11A	RAB11A	RAB11A	8956	0.03	0.26	NO
16	ARHGDIA	ARHGDIA	ARHGDIA	10625	0.0049	0.19	NO
17	STX4	STX4	STX4	11354	-0.0049	0.16	NO
18	DYNC1LI2	DYNC1LI2	DYNC1LI2	11885	-0.012	0.14	NO
19	DCTN6	DCTN6	DCTN6	12008	-0.014	0.14	NO
20	DYNLL2	DYNLL2	DYNLL2	12099	-0.015	0.13	NO
21	RAB5B	RAB5B	RAB5B	12491	-0.021	0.12	NO
22	CREB1	CREB1	CREB1	12507	-0.021	0.12	NO
23	DYNC1I2	DYNC1I2	DYNC1I2	12907	-0.026	0.11	NO
24	DCTN5	DCTN5	DCTN5	13439	-0.033	0.09	NO
25	DCTN4	DCTN4	DCTN4	13939	-0.041	0.073	NO
26	PRKACB	PRKACB	PRKACB	13949	-0.041	0.079	NO
27	ADCY9	ADCY9	ADCY9	13976	-0.041	0.083	NO
28	GNAS	GNAS	GNAS	14053	-0.042	0.086	NO
29	RAB11B	RAB11B	RAB11B	14080	-0.043	0.091	NO
30	DYNC1LI1	DYNC1LI1	DYNC1LI1	14605	-0.051	0.075	NO
31	DYNC1H1	DYNC1H1	DYNC1H1	14907	-0.056	0.07	NO
32	VAMP2	VAMP2	VAMP2	15506	-0.067	0.053	NO
33	DCTN2	DCTN2	DCTN2	15645	-0.069	0.056	NO
34	DCTN1	DCTN1	DCTN1	15737	-0.071	0.062	NO
35	PRKACA	PRKACA	PRKACA	15975	-0.076	0.063	NO
36	AQP4	AQP4	AQP4	16014	-0.077	0.072	NO
37	DYNLL1	DYNLL1	DYNLL1	16135	-0.079	0.077	NO
38	PRKX	PRKX	PRKX	19250	-0.19	-0.033	NO
39	DYNC2H1	DYNC2H1	DYNC2H1	19663	-0.21	-0.021	NO
40	CREB5	CREB5	CREB5	20603	-0.3	-0.021	NO
41	AQP3	AQP3	AQP3	21157	-0.36	0.0056	NO
42	DYNC1I1	DYNC1I1	DYNC1I1	21835	-0.49	0.044	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 PPARA PATHWAY.

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

genes ES table in pathway: BIOCARTA RHO PATHWAY

Table 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	ACSL5	ACSL5	ACSL5	390	0.78	0.056	YES
2	AGXT	AGXT	AGXT	403	0.77	0.13	YES
3	BAAT	BAAT	BAAT	464	0.72	0.19	YES
4	NOS2	NOS2	NOS2	574	0.66	0.25	YES
5	SLC27A2	SLC27A2	SLC27A2	707	0.6	0.3	YES
6	FAR2	FAR2	FAR2	881	0.53	0.34	YES
7	HAO2	HAO2	HAO2	1025	0.49	0.38	YES
8	DDO	DDO	DDO	2328	0.27	0.35	YES
9	PIPOX	PIPOX	PIPOX	2414	0.27	0.38	YES
10	PHYH	PHYH	PHYH	2482	0.26	0.4	YES
11	EPHX2	EPHX2	EPHX2	3449	0.19	0.37	YES
12	PEX11A	PEX11A	PEX11A	3601	0.18	0.38	YES
13	DECR2	DECR2	DECR2	3900	0.17	0.39	YES
14	ABCD1	ABCD1	ABCD1	4084	0.16	0.39	YES
15	ABCD3	ABCD3	ABCD3	4124	0.16	0.41	YES
16	AMACR	AMACR	AMACR	4406	0.15	0.41	YES
17	HACL1	HACL1	HACL1	4580	0.14	0.41	YES
18	CAT	CAT	CAT	4629	0.14	0.42	YES
19	ACAA1	ACAA1	ACAA1	4643	0.14	0.44	YES
20	PEX11G	PEX11G	PEX11G	4796	0.13	0.44	YES
21	ACOX1	ACOX1	ACOX1	4799	0.13	0.46	YES
22	NUDT12	NUDT12	NUDT12	5020	0.12	0.46	YES
23	IDH1	IDH1	IDH1	5204	0.12	0.46	YES
24	HMGCL	HMGCL	HMGCL	5219	0.12	0.47	YES
25	CRAT	CRAT	CRAT	5262	0.11	0.48	YES
26	PEX7	PEX7	PEX7	5341	0.11	0.48	YES
27	PECR	PECR	PECR	5480	0.11	0.49	YES
28	MLYCD	MLYCD	MLYCD	5595	0.1	0.49	YES
29	GSTK1	GSTK1	GSTK1	5691	0.099	0.5	YES
30	SCP2	SCP2	SCP2	5700	0.098	0.51	YES
31	PXMP4	PXMP4	PXMP4	5760	0.097	0.52	YES
32	ABCD2	ABCD2	ABCD2	5771	0.097	0.52	YES
33	ABCD4	ABCD4	ABCD4	6220	0.084	0.51	NO
34	DAO	DAO	DAO	6337	0.081	0.51	NO
35	PEX1	PEX1	PEX1	6415	0.08	0.52	NO
36	PXMP2	PXMP2	PXMP2	6538	0.076	0.52	NO
37	IDH2	IDH2	IDH2	7191	0.062	0.5	NO
38	ACOT8	ACOT8	ACOT8	7204	0.062	0.5	NO
39	GNPAT	GNPAT	GNPAT	7345	0.059	0.5	NO
40	ACSL4	ACSL4	ACSL4	8271	0.041	0.47	NO
41	HSD17B4	HSD17B4	HSD17B4	8490	0.038	0.46	NO
42	PEX2	PEX2	PEX2	8724	0.034	0.45	NO
43	ACSL6	ACSL6	ACSL6	8725	0.034	0.46	NO
44	PEX16	PEX16	PEX16	8735	0.034	0.46	NO
45	ACSL3	ACSL3	ACSL3	8758	0.033	0.46	NO
46	PEX6	PEX6	PEX6	8890	0.031	0.46	NO
47	AGPS	AGPS	AGPS	9477	0.021	0.43	NO
48	PEX11B	PEX11B	PEX11B	9770	0.017	0.42	NO
49	FAR1	FAR1	FAR1	10465	0.0071	0.39	NO
50	PEX26	PEX26	PEX26	11166	-0.0023	0.36	NO
51	ACOX3	ACOX3	ACOX3	11304	-0.0042	0.36	NO
52	PEX10	PEX10	PEX10	12107	-0.015	0.32	NO
53	XDH	XDH	XDH	13030	-0.028	0.28	NO
54	PEX12	PEX12	PEX12	13065	-0.028	0.29	NO
55	EHHADH	EHHADH	EHHADH	13171	-0.029	0.28	NO
56	SOD1	SOD1	SOD1	13236	-0.03	0.28	NO
57	PMVK	PMVK	PMVK	13622	-0.036	0.27	NO
58	PEX3	PEX3	PEX3	13822	-0.039	0.27	NO
59	PEX14	PEX14	PEX14	13962	-0.041	0.26	NO
60	SOD2	SOD2	SOD2	14313	-0.046	0.25	NO
61	PEX13	PEX13	PEX13	14351	-0.047	0.26	NO
62	PEX5	PEX5	PEX5	14662	-0.052	0.25	NO
63	PRDX5	PRDX5	PRDX5	14924	-0.057	0.24	NO
64	PAOX	PAOX	PAOX	16201	-0.08	0.19	NO
65	MPV17	MPV17	MPV17	16235	-0.081	0.2	NO
66	NUDT19	NUDT19	NUDT19	16373	-0.084	0.2	NO
67	PRDX1	PRDX1	PRDX1	16655	-0.091	0.2	NO
68	SLC25A17	SLC25A17	SLC25A17	17002	-0.1	0.19	NO
69	ACSL1	ACSL1	ACSL1	17780	-0.12	0.17	NO
70	DHRS4	DHRS4	DHRS4	17943	-0.13	0.17	NO
71	MPV17L	MPV17L	MPV17L	18030	-0.13	0.18	NO
72	MVK	MVK	MVK	18062	-0.13	0.19	NO
73	CROT	CROT	CROT	18891	-0.17	0.17	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 RHO PATHWAY.

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

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	PIP5K1B	PIP5K1B	PIP5K1B	114	1.2	0.35	YES
2	ARHGAP6	ARHGAP6	ARHGAP6	873	0.53	0.47	YES
3	ARHGAP4	ARHGAP4	ARHGAP4	3490	0.19	0.41	NO
4	SRC	SRC	SRC	4971	0.12	0.38	NO
5	ARPC1B	ARPC1B	ARPC1B	7282	0.06	0.29	NO
6	RHOA	RHOA	RHOA	7532	0.055	0.3	NO
7	PPP1R12B	PPP1R12B	PPP1R12B	7709	0.051	0.31	NO
8	ARHGEF11	ARHGEF11	ARHGEF11	8059	0.045	0.3	NO
9	ARHGEF1	ARHGEF1	ARHGEF1	8238	0.042	0.31	NO
10	ROCK1	ROCK1	ROCK1	8836	0.032	0.29	NO
11	DIAPH1	DIAPH1	DIAPH1	9383	0.023	0.27	NO
12	OPHN1	OPHN1	OPHN1	10554	0.0061	0.22	NO
13	CFL1	CFL1	CFL1	10781	0.0027	0.22	NO
14	ACTR2	ACTR2	ACTR2	11060	-0.00092	0.2	NO
15	ARPC5	ARPC5	ARPC5	11210	-0.0029	0.2	NO
16	ARPC1A	ARPC1A	ARPC1A	11249	-0.0035	0.2	NO
17	ARHGAP5	ARHGAP5	ARHGAP5	11458	-0.0063	0.19	NO
18	MYL2	MYL2	MYL2	11878	-0.012	0.18	NO
19	ARPC3	ARPC3	ARPC3	12913	-0.026	0.14	NO
20	PFN1	PFN1	PFN1	12932	-0.026	0.14	NO
21	PIP5K1A	PIP5K1A	PIP5K1A	13303	-0.031	0.14	NO
22	VCL	VCL	VCL	13637	-0.036	0.13	NO
23	GSN	GSN	GSN	13968	-0.041	0.13	NO
24	ARHGAP1	ARHGAP1	ARHGAP1	14414	-0.048	0.12	NO
25	ACTR3	ACTR3	ACTR3	15106	-0.06	0.11	NO
26	ARPC2	ARPC2	ARPC2	15232	-0.062	0.12	NO
27	LIMK1	LIMK1	LIMK1	18076	-0.14	0.038	NO
28	ARHGEF5	ARHGEF5	ARHGEF5	18392	-0.15	0.066	NO
29	MYLK	MYLK	MYLK	19248	-0.19	0.083	NO
30	BAIAP2	BAIAP2	BAIAP2	20245	-0.26	0.11	NO

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

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

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

Table 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	ACY3	ACY3	ACY3	258	0.91	0.13	YES
2	AGXT	AGXT	AGXT	403	0.77	0.25	YES
3	GPT	GPT	GPT	1012	0.49	0.3	YES
4	CPS1	CPS1	CPS1	1235	0.43	0.36	YES
5	GAD1	GAD1	GAD1	1339	0.41	0.42	YES
6	ASL	ASL	ASL	1383	0.4	0.48	YES
7	ASS1	ASS1	ASS1	1706	0.34	0.52	YES
8	DDO	DDO	DDO	2328	0.27	0.54	YES
9	GFPT1	GFPT1	GFPT1	2468	0.26	0.57	YES
10	ASPA	ASPA	ASPA	4586	0.14	0.5	NO
11	ABAT	ABAT	ABAT	4616	0.14	0.52	NO
12	ALDH5A1	ALDH5A1	ALDH5A1	6813	0.07	0.44	NO
13	GLS	GLS	GLS	9482	0.021	0.32	NO
14	GAD2	GAD2	GAD2	9809	0.016	0.31	NO
15	GLUD2	GLUD2	GLUD2	9908	0.015	0.31	NO
16	GOT1	GOT1	GOT1	9913	0.015	0.31	NO
17	AGXT2	AGXT2	AGXT2	10085	0.012	0.31	NO
18	ASNS	ASNS	ASNS	10238	0.01	0.3	NO
19	IL4I1	IL4I1	IL4I1	12566	-0.022	0.2	NO
20	PPAT	PPAT	PPAT	13352	-0.032	0.18	NO
21	CAD	CAD	CAD	14709	-0.053	0.12	NO
22	GLUD1	GLUD1	GLUD1	14997	-0.058	0.12	NO
23	GPT2	GPT2	GPT2	15032	-0.058	0.13	NO
24	ADSL	ADSL	ADSL	15797	-0.072	0.11	NO
25	GOT2	GOT2	GOT2	16912	-0.098	0.073	NO
26	NIT2	NIT2	NIT2	16985	-0.1	0.086	NO
27	GLS2	GLS2	GLS2	17164	-0.1	0.095	NO
28	GLUL	GLUL	GLUL	18594	-0.16	0.057	NO
29	ALDH4A1	ALDH4A1	ALDH4A1	19128	-0.18	0.062	NO
30	ADSSL1	ADSSL1	ADSSL1	19263	-0.19	0.086	NO
31	GFPT2	GFPT2	GFPT2	21639	-0.45	0.053	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table 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	LDHAL6A	LDHAL6A	LDHAL6A	1658	0.35	0.032	YES
2	LDHAL6B	LDHAL6B	LDHAL6B	1715	0.34	0.13	YES
3	ACACB	ACACB	ACACB	2023	0.31	0.21	YES
4	SUCLG2	SUCLG2	SUCLG2	2898	0.23	0.24	YES
5	ALDH2	ALDH2	ALDH2	3331	0.2	0.28	YES
6	ACSS1	ACSS1	ACSS1	3429	0.19	0.33	YES
7	ACSS2	ACSS2	ACSS2	3879	0.17	0.36	YES
8	ABAT	ABAT	ABAT	4616	0.14	0.37	YES
9	PCCA	PCCA	PCCA	4748	0.13	0.4	YES
10	ALDH1B1	ALDH1B1	ALDH1B1	5066	0.12	0.42	YES
11	MLYCD	MLYCD	MLYCD	5595	0.1	0.43	YES
12	ECHS1	ECHS1	ECHS1	5882	0.093	0.45	YES
13	ACAT1	ACAT1	ACAT1	6109	0.088	0.46	YES
14	SUCLG1	SUCLG1	SUCLG1	6195	0.085	0.48	YES
15	HIBCH	HIBCH	HIBCH	6984	0.067	0.47	NO
16	ALDH6A1	ALDH6A1	ALDH6A1	7350	0.059	0.47	NO
17	MCEE	MCEE	MCEE	8663	0.035	0.42	NO
18	ALDH9A1	ALDH9A1	ALDH9A1	10313	0.0092	0.36	NO
19	HADHA	HADHA	HADHA	10503	0.0067	0.35	NO
20	ACADM	ACADM	ACADM	10820	0.0022	0.34	NO
21	SUCLA2	SUCLA2	SUCLA2	10948	0.00058	0.33	NO
22	ACSS3	ACSS3	ACSS3	11066	-0.001	0.33	NO
23	MUT	MUT	MUT	11177	-0.0024	0.32	NO
24	ALDH7A1	ALDH7A1	ALDH7A1	11472	-0.0065	0.31	NO
25	EHHADH	EHHADH	EHHADH	13171	-0.029	0.24	NO
26	PCCB	PCCB	PCCB	14719	-0.053	0.19	NO
27	ACAT2	ACAT2	ACAT2	15186	-0.061	0.19	NO
28	ACACA	ACACA	ACACA	16253	-0.081	0.17	NO
29	LDHA	LDHA	LDHA	16293	-0.082	0.19	NO
30	ALDH3A2	ALDH3A2	ALDH3A2	17631	-0.12	0.17	NO
31	LDHB	LDHB	LDHB	19558	-0.21	0.14	NO

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

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

genes ES table in pathway: KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM

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	UGT2B7	UGT2B7	UGT2B7	154	1.1	0.097	YES
2	SI	SI	SI	210	1	0.19	YES
3	UGT2A3	UGT2A3	UGT2A3	220	0.98	0.28	YES
4	UGT2B15	UGT2B15	UGT2B15	235	0.95	0.37	YES
5	MGAM	MGAM	MGAM	452	0.73	0.43	YES
6	GBA3	GBA3	GBA3	665	0.62	0.48	YES
7	TREH	TREH	TREH	699	0.6	0.53	YES
8	G6PC2	G6PC2	G6PC2	1171	0.44	0.55	YES
9	ENPP1	ENPP1	ENPP1	1189	0.44	0.59	YES
10	UGT2B17	UGT2B17	UGT2B17	1390	0.4	0.62	YES
11	UGT2B11	UGT2B11	UGT2B11	2205	0.29	0.61	NO
12	PGM2L1	PGM2L1	PGM2L1	2576	0.25	0.62	NO
13	ENPP3	ENPP3	ENPP3	3129	0.21	0.62	NO
14	AMY2B	AMY2B	AMY2B	4050	0.16	0.59	NO
15	GUSB	GUSB	GUSB	4505	0.14	0.58	NO
16	UGT2B4	UGT2B4	UGT2B4	5722	0.098	0.54	NO
17	PYGB	PYGB	PYGB	6754	0.072	0.5	NO
18	G6PC	G6PC	G6PC	8679	0.035	0.42	NO
19	PYGM	PYGM	PYGM	9667	0.019	0.38	NO
20	UGDH	UGDH	UGDH	10318	0.0091	0.35	NO
21	UGP2	UGP2	UGP2	11127	-0.0018	0.32	NO
22	UGT1A1	UGT1A1	UGT1A1	11191	-0.0026	0.32	NO
23	PGM1	PGM1	PGM1	11737	-0.01	0.29	NO
24	GCK	GCK	GCK	13631	-0.036	0.21	NO
25	HK2	HK2	HK2	15033	-0.059	0.16	NO
26	GANC	GANC	GANC	15868	-0.074	0.13	NO
27	GPI	GPI	GPI	15887	-0.074	0.13	NO
28	AGL	AGL	AGL	16101	-0.078	0.13	NO
29	GBE1	GBE1	GBE1	16157	-0.08	0.14	NO
30	GYS1	GYS1	GYS1	16872	-0.097	0.11	NO
31	HK3	HK3	HK3	17211	-0.11	0.11	NO
32	UGT2B28	UGT2B28	UGT2B28	17761	-0.12	0.096	NO
33	PGM2	PGM2	PGM2	17831	-0.13	0.1	NO
34	GYS2	GYS2	GYS2	18614	-0.16	0.086	NO
35	GAA	GAA	GAA	19267	-0.19	0.075	NO
36	HK1	HK1	HK1	19416	-0.2	0.087	NO
37	UGT2A1	UGT2A1	UGT2A1	19706	-0.22	0.094	NO
38	PYGL	PYGL	PYGL	21718	-0.46	0.05	NO

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

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ALANINE ASPARTATE AND GLUTAMATE 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 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	HMGCS2	HMGCS2	HMGCS2	142	1.1	0.22	YES
2	ACAA2	ACAA2	ACAA2	1147	0.45	0.27	YES
3	ALDH2	ALDH2	ALDH2	3331	0.2	0.21	YES
4	BCKDHB	BCKDHB	BCKDHB	3337	0.2	0.25	YES
5	ACADS	ACADS	ACADS	3636	0.18	0.27	YES
6	IVD	IVD	IVD	3882	0.17	0.3	YES
7	HIBADH	HIBADH	HIBADH	4214	0.16	0.31	YES
8	ABAT	ABAT	ABAT	4616	0.14	0.32	YES
9	ACAA1	ACAA1	ACAA1	4643	0.14	0.35	YES
10	ACAD8	ACAD8	ACAD8	4718	0.13	0.37	YES
11	PCCA	PCCA	PCCA	4748	0.13	0.4	YES
12	ALDH1B1	ALDH1B1	ALDH1B1	5066	0.12	0.41	YES
13	ACADSB	ACADSB	ACADSB	5071	0.12	0.43	YES
14	HMGCL	HMGCL	HMGCL	5219	0.12	0.45	YES
15	ECHS1	ECHS1	ECHS1	5882	0.093	0.44	YES
16	ACAT1	ACAT1	ACAT1	6109	0.088	0.44	YES
17	HADH	HADH	HADH	6333	0.081	0.45	YES
18	MCCC2	MCCC2	MCCC2	6883	0.069	0.44	YES
19	HIBCH	HIBCH	HIBCH	6984	0.067	0.45	YES
20	AUH	AUH	AUH	7138	0.064	0.45	YES
21	ALDH6A1	ALDH6A1	ALDH6A1	7350	0.059	0.46	YES
22	OXCT2	OXCT2	OXCT2	8122	0.044	0.43	NO
23	MCEE	MCEE	MCEE	8663	0.035	0.41	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	10313	0.0092	0.34	NO
25	BCAT2	BCAT2	BCAT2	10496	0.0068	0.34	NO
26	HADHA	HADHA	HADHA	10503	0.0067	0.34	NO
27	ACADM	ACADM	ACADM	10820	0.0022	0.32	NO
28	MUT	MUT	MUT	11177	-0.0024	0.31	NO
29	ALDH7A1	ALDH7A1	ALDH7A1	11472	-0.0065	0.3	NO
30	HSD17B10	HSD17B10	HSD17B10	11673	-0.0092	0.29	NO
31	IL4I1	IL4I1	IL4I1	12566	-0.022	0.26	NO
32	DLD	DLD	DLD	12660	-0.023	0.26	NO
33	EHHADH	EHHADH	EHHADH	13171	-0.029	0.24	NO
34	HMGCS1	HMGCS1	HMGCS1	13946	-0.041	0.21	NO
35	AOX1	AOX1	AOX1	14295	-0.046	0.21	NO
36	PCCB	PCCB	PCCB	14719	-0.053	0.2	NO
37	HADHB	HADHB	HADHB	14864	-0.056	0.2	NO
38	ACAT2	ACAT2	ACAT2	15186	-0.061	0.2	NO
39	MCCC1	MCCC1	MCCC1	16741	-0.094	0.15	NO
40	DBT	DBT	DBT	17157	-0.1	0.16	NO
41	ALDH3A2	ALDH3A2	ALDH3A2	17631	-0.12	0.16	NO
42	BCKDHA	BCKDHA	BCKDHA	17972	-0.13	0.17	NO
43	OXCT1	OXCT1	OXCT1	19721	-0.22	0.14	NO

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

Figure S18. 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 HISTIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GAS2	GAS2	GAS2	379	0.79	0.17	YES
2	BIRC3	BIRC3	BIRC3	1180	0.44	0.24	YES
3	CASP10	CASP10	CASP10	1324	0.41	0.32	YES
4	DFFB	DFFB	DFFB	2411	0.27	0.34	YES
5	APAF1	APAF1	APAF1	2904	0.23	0.37	YES
6	CASP6	CASP6	CASP6	3841	0.17	0.37	YES
7	CASP8	CASP8	CASP8	4575	0.14	0.37	YES
8	CASP7	CASP7	CASP7	5314	0.11	0.36	YES
9	SPTAN1	SPTAN1	SPTAN1	5863	0.094	0.36	YES
10	MAP3K14	MAP3K14	MAP3K14	5942	0.092	0.38	YES
11	TNFRSF10B	TNFRSF10B	TNFRSF10B	6372	0.08	0.38	YES
12	TRAF2	TRAF2	TRAF2	6375	0.08	0.4	YES
13	TNFRSF10A	TNFRSF10A	TNFRSF10A	6564	0.076	0.41	YES
14	CHUK	CHUK	CHUK	6601	0.075	0.42	YES
15	CASP9	CASP9	CASP9	6639	0.074	0.44	YES
16	CFLAR	CFLAR	CFLAR	6939	0.068	0.44	YES
17	CASP3	CASP3	CASP3	7248	0.061	0.44	YES
18	CYCS	CYCS	CYCS	7429	0.057	0.45	YES
19	XIAP	XIAP	XIAP	7541	0.055	0.46	YES
20	RIPK1	RIPK1	RIPK1	8648	0.035	0.42	NO
21	BIRC2	BIRC2	BIRC2	10331	0.0089	0.34	NO
22	DFFA	DFFA	DFFA	10688	0.0039	0.33	NO
23	RELA	RELA	RELA	12557	-0.022	0.25	NO
24	NFKB1	NFKB1	NFKB1	12772	-0.024	0.25	NO
25	TNFRSF25	TNFRSF25	TNFRSF25	12990	-0.027	0.24	NO
26	LMNA	LMNA	LMNA	13972	-0.041	0.21	NO
27	TRADD	TRADD	TRADD	16302	-0.083	0.13	NO
28	BCL2	BCL2	BCL2	17168	-0.1	0.12	NO
29	NFKBIA	NFKBIA	NFKBIA	18285	-0.14	0.1	NO
30	TNFSF10	TNFSF10	TNFSF10	19481	-0.2	0.094	NO
31	FADD	FADD	FADD	19872	-0.23	0.13	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA CARM ER PATHWAY	33	genes.ES.table	0.38	1.4	0.14	0.69	0.88	0.61	0.45	0.33	0.55	0.27
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.5	1.7	0.021	0.63	0.49	0.19	0.12	0.17	0	0.22
BIOCARTA GSK3 PATHWAY	25	genes.ES.table	0.39	1.3	0.14	0.69	0.9	0.36	0.3	0.25	0.57	0.27
BIOCARTA INTEGRIN PATHWAY	37	genes.ES.table	0.37	1.4	0.1	0.66	0.82	0.11	0.078	0.1	0.48	0.26
BIOCARTA MYOSIN PATHWAY	30	genes.ES.table	0.51	1.7	0.017	0.62	0.4	0.17	0.1	0.15	0	0.22
KEGG RNA DEGRADATION	56	genes.ES.table	0.36	1.4	0.14	0.67	0.88	0.62	0.52	0.3	0.55	0.25
KEGG CELL CYCLE	117	genes.ES.table	0.35	1.4	0.15	0.66	0.84	0.67	0.44	0.37	0.49	0.25
KEGG OOCYTE MEIOSIS	107	genes.ES.table	0.36	1.5	0.055	0.86	0.73	0.43	0.36	0.28	0.55	0.32
KEGG P53 SIGNALING PATHWAY	66	genes.ES.table	0.36	1.4	0.1	0.66	0.81	0.46	0.33	0.3	0.48	0.26
KEGG MTOR SIGNALING PATHWAY	49	genes.ES.table	0.35	1.4	0.12	0.65	0.85	0.2	0.2	0.16	0.5	0.24

genes ES table in pathway: BIOCARTA CARM ER 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	NTF4	NTF4	NTF4	56	0.74	0.049	YES
2	NGFR	NGFR	NGFR	93	0.69	0.096	YES
3	CALML3	CALML3	CALML3	145	0.64	0.14	YES
4	NTRK2	NTRK2	NTRK2	309	0.56	0.17	YES
5	NGF	NGF	NGF	366	0.54	0.2	YES
6	TP73	TP73	TP73	563	0.48	0.23	YES
7	CAMK2B	CAMK2B	CAMK2B	732	0.45	0.25	YES
8	NGFRAP1	NGFRAP1	NGFRAP1	786	0.44	0.28	YES
9	IRS4	IRS4	IRS4	842	0.43	0.31	YES
10	CAMK4	CAMK4	CAMK4	1061	0.4	0.33	YES
11	MAPK10	MAPK10	MAPK10	1168	0.38	0.35	YES
12	CALML5	CALML5	CALML5	1188	0.38	0.38	YES
13	RPS6KA6	RPS6KA6	RPS6KA6	1741	0.32	0.38	YES
14	CAMK2A	CAMK2A	CAMK2A	1743	0.32	0.4	YES
15	MAPK12	MAPK12	MAPK12	2176	0.28	0.4	YES
16	AKT3	AKT3	AKT3	2236	0.28	0.42	YES
17	MAPK11	MAPK11	MAPK11	2271	0.28	0.43	YES
18	PIK3CD	PIK3CD	PIK3CD	3268	0.21	0.4	NO
19	CALML6	CALML6	CALML6	3337	0.21	0.42	NO
20	SHC4	SHC4	SHC4	3429	0.2	0.42	NO
21	BDNF	BDNF	BDNF	4358	0.17	0.4	NO
22	PDK1	PDK1	PDK1	4449	0.16	0.4	NO
23	BCL2	BCL2	BCL2	4470	0.16	0.41	NO
24	IRS2	IRS2	IRS2	4530	0.16	0.42	NO
25	PIK3CA	PIK3CA	PIK3CA	4650	0.16	0.43	NO
26	SH2B2	SH2B2	SH2B2	4932	0.15	0.43	NO
27	CRKL	CRKL	CRKL	5909	0.12	0.39	NO
28	RPS6KA5	RPS6KA5	RPS6KA5	6141	0.11	0.39	NO
29	YWHAG	YWHAG	YWHAG	6505	0.1	0.38	NO
30	YWHAQ	YWHAQ	YWHAQ	6566	0.1	0.38	NO
31	NTRK3	NTRK3	NTRK3	6608	0.1	0.39	NO
32	TP53	TP53	TP53	6654	0.1	0.4	NO
33	NFKBIA	NFKBIA	NFKBIA	6815	0.098	0.4	NO
34	PLCG1	PLCG1	PLCG1	6851	0.098	0.4	NO
35	NTRK1	NTRK1	NTRK1	6902	0.097	0.4	NO
36	IRS1	IRS1	IRS1	6996	0.095	0.41	NO
37	SHC3	SHC3	SHC3	7079	0.094	0.41	NO
38	ZNF274	ZNF274	ZNF274	7383	0.089	0.4	NO
39	KIDINS220	KIDINS220	KIDINS220	7428	0.088	0.41	NO
40	MAPK7	MAPK7	MAPK7	7556	0.086	0.41	NO
41	SHC1	SHC1	SHC1	7756	0.082	0.4	NO
42	GSK3B	GSK3B	GSK3B	7774	0.082	0.41	NO
43	YWHAE	YWHAE	YWHAE	7781	0.082	0.42	NO
44	RAPGEF1	RAPGEF1	RAPGEF1	7920	0.08	0.41	NO
45	JUN	JUN	JUN	8055	0.078	0.41	NO
46	MAP2K7	MAP2K7	MAP2K7	8344	0.074	0.41	NO
47	ABL1	ABL1	ABL1	8497	0.071	0.4	NO
48	FRS2	FRS2	FRS2	8728	0.068	0.4	NO
49	BRAF	BRAF	BRAF	8799	0.067	0.4	NO
50	BAD	BAD	BAD	9013	0.064	0.4	NO
51	PIK3R2	PIK3R2	PIK3R2	9675	0.056	0.37	NO
52	MAPK1	MAPK1	MAPK1	9913	0.053	0.36	NO
53	PIK3R1	PIK3R1	PIK3R1	9986	0.052	0.36	NO
54	MAP3K3	MAP3K3	MAP3K3	10019	0.052	0.37	NO
55	YWHAH	YWHAH	YWHAH	10674	0.044	0.34	NO
56	SOS2	SOS2	SOS2	10698	0.044	0.34	NO
57	AKT2	AKT2	AKT2	10883	0.042	0.34	NO
58	MAP2K5	MAP2K5	MAP2K5	10972	0.041	0.34	NO
59	AKT1	AKT1	AKT1	11073	0.04	0.34	NO
60	CRK	CRK	CRK	11144	0.039	0.34	NO
61	SOS1	SOS1	SOS1	11312	0.037	0.33	NO
62	PLCG2	PLCG2	PLCG2	11405	0.036	0.33	NO
63	NFKB1	NFKB1	NFKB1	11569	0.033	0.32	NO
64	MAP2K1	MAP2K1	MAP2K1	11573	0.033	0.33	NO
65	YWHAZ	YWHAZ	YWHAZ	11670	0.032	0.32	NO
66	PTPN11	PTPN11	PTPN11	11689	0.032	0.32	NO
67	RAP1B	RAP1B	RAP1B	11775	0.031	0.32	NO
68	ATF4	ATF4	ATF4	12481	0.023	0.29	NO
69	GAB1	GAB1	GAB1	12488	0.022	0.3	NO
70	RPS6KA4	RPS6KA4	RPS6KA4	12543	0.022	0.29	NO
71	ARHGDIB	ARHGDIB	ARHGDIB	12572	0.022	0.3	NO
72	PRDM4	PRDM4	PRDM4	12629	0.021	0.29	NO
73	MAP2K2	MAP2K2	MAP2K2	12740	0.02	0.29	NO
74	RELA	RELA	RELA	12814	0.019	0.29	NO
75	RAP1A	RAP1A	RAP1A	13042	0.016	0.28	NO
76	MAGED1	MAGED1	MAGED1	13043	0.016	0.28	NO
77	MAP3K1	MAP3K1	MAP3K1	13099	0.016	0.28	NO
78	CDC42	CDC42	CDC42	13322	0.013	0.27	NO
79	NRAS	NRAS	NRAS	13424	0.012	0.27	NO
80	IKBKB	IKBKB	IKBKB	13511	0.011	0.26	NO
81	IRAK4	IRAK4	IRAK4	13610	0.0099	0.26	NO
82	CAMK2G	CAMK2G	CAMK2G	13717	0.0086	0.26	NO
83	MAPKAPK2	MAPKAPK2	MAPKAPK2	13747	0.0082	0.26	NO
84	SH2B1	SH2B1	SH2B1	13793	0.0076	0.25	NO
85	PIK3R5	PIK3R5	PIK3R5	13870	0.0067	0.25	NO
86	CAMK2D	CAMK2D	CAMK2D	13897	0.0063	0.25	NO
87	CALM1	CALM1	CALM1	13930	0.0058	0.25	NO
88	SHC2	SHC2	SHC2	14196	0.0026	0.24	NO
89	IRAK1	IRAK1	IRAK1	14368	0.00037	0.23	NO
90	MAPK9	MAPK9	MAPK9	14469	-0.00082	0.23	NO
91	CALM2	CALM2	CALM2	14661	-0.0032	0.22	NO
92	GRB2	GRB2	GRB2	14676	-0.0035	0.22	NO
93	MAPK14	MAPK14	MAPK14	14908	-0.0067	0.21	NO
94	TRAF6	TRAF6	TRAF6	15200	-0.011	0.2	NO
95	MAP3K5	MAP3K5	MAP3K5	15208	-0.011	0.2	NO
96	PIK3CB	PIK3CB	PIK3CB	15400	-0.014	0.19	NO
97	ARHGDIA	ARHGDIA	ARHGDIA	15554	-0.016	0.18	NO
98	RAC1	RAC1	RAC1	15641	-0.018	0.18	NO
99	SH2B3	SH2B3	SH2B3	15708	-0.018	0.18	NO
100	YWHAB	YWHAB	YWHAB	15913	-0.021	0.17	NO
101	RPS6KA1	RPS6KA1	RPS6KA1	15937	-0.022	0.17	NO
102	NTF3	NTF3	NTF3	16079	-0.024	0.17	NO
103	RAF1	RAF1	RAF1	16087	-0.024	0.17	NO
104	MAPK8	MAPK8	MAPK8	16187	-0.026	0.17	NO
105	CSK	CSK	CSK	16727	-0.036	0.14	NO
106	IRAK3	IRAK3	IRAK3	16746	-0.036	0.15	NO
107	PSEN1	PSEN1	PSEN1	16764	-0.036	0.15	NO
108	RIPK2	RIPK2	RIPK2	16781	-0.037	0.15	NO
109	BAX	BAX	BAX	16858	-0.039	0.15	NO
110	FOXO3	FOXO3	FOXO3	16998	-0.041	0.15	NO
111	PIK3R3	PIK3R3	PIK3R3	17278	-0.048	0.14	NO
112	RHOA	RHOA	RHOA	17320	-0.048	0.14	NO
113	KRAS	KRAS	KRAS	17433	-0.051	0.14	NO
114	FASLG	FASLG	FASLG	17659	-0.056	0.13	NO
115	NFKBIB	NFKBIB	NFKBIB	17674	-0.056	0.14	NO
116	MAPK13	MAPK13	MAPK13	18241	-0.073	0.12	NO
117	CALM3	CALM3	CALM3	18462	-0.079	0.11	NO
118	RPS6KA2	RPS6KA2	RPS6KA2	18604	-0.084	0.11	NO
119	RPS6KA3	RPS6KA3	RPS6KA3	18987	-0.099	0.1	NO
120	NFKBIE	NFKBIE	NFKBIE	19252	-0.11	0.097	NO
121	MAPK3	MAPK3	MAPK3	19738	-0.13	0.084	NO
122	PIK3CG	PIK3CG	PIK3CG	19851	-0.14	0.089	NO
123	PRKCD	PRKCD	PRKCD	19895	-0.14	0.097	NO
124	SORT1	SORT1	SORT1	20413	-0.17	0.086	NO
125	IRAK2	IRAK2	IRAK2	21600	-0.3	0.055	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 CARM ER PATHWAY.

Figure S22. 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 ERK 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	GNGT1	GNGT1	GNGT1	232	0.59	0.17	YES
2	ARHGEF4	ARHGEF4	ARHGEF4	794	0.44	0.28	YES
3	MYL7	MYL7	MYL7	1305	0.36	0.37	YES
4	ARHGEF19	ARHGEF19	ARHGEF19	1884	0.31	0.44	YES
5	MYLK	MYLK	MYLK	2290	0.27	0.51	YES
6	GNA12	GNA12	GNA12	6408	0.11	0.36	NO
7	ARHGEF10	ARHGEF10	ARHGEF10	7782	0.082	0.32	NO
8	ARHGEF17	ARHGEF17	ARHGEF17	7854	0.081	0.34	NO
9	ARHGEF5	ARHGEF5	ARHGEF5	8725	0.068	0.33	NO
10	ARHGEF6	ARHGEF6	ARHGEF6	8902	0.066	0.34	NO
11	PPP1R12B	PPP1R12B	PPP1R12B	10687	0.044	0.28	NO
12	GNB1	GNB1	GNB1	11013	0.04	0.27	NO
13	ROCK1	ROCK1	ROCK1	11940	0.029	0.24	NO
14	PKN1	PKN1	PKN1	13454	0.012	0.18	NO
15	PLCB1	PLCB1	PLCB1	14091	0.0039	0.15	NO
16	ARHGAP5	ARHGAP5	ARHGAP5	14693	-0.0037	0.13	NO
17	ARHGEF3	ARHGEF3	ARHGEF3	14860	-0.006	0.12	NO
18	ARHGEF11	ARHGEF11	ARHGEF11	15285	-0.012	0.11	NO
19	PRKCB	PRKCB	PRKCB	15728	-0.019	0.093	NO
20	ARHGEF9	ARHGEF9	ARHGEF9	16126	-0.025	0.083	NO
21	ARHGEF7	ARHGEF7	ARHGEF7	16405	-0.03	0.08	NO
22	ARHGEF1	ARHGEF1	ARHGEF1	16452	-0.031	0.088	NO
23	MYL2	MYL2	MYL2	16463	-0.031	0.097	NO
24	ARHGEF18	ARHGEF18	ARHGEF18	16538	-0.032	0.1	NO
25	ARHGEF12	ARHGEF12	ARHGEF12	16590	-0.033	0.11	NO
26	GNAQ	GNAQ	GNAQ	16993	-0.041	0.11	NO
27	ARHGEF2	ARHGEF2	ARHGEF2	17276	-0.048	0.11	NO
28	ARHGEF16	ARHGEF16	ARHGEF16	19787	-0.13	0.04	NO
29	ARHGEF15	ARHGEF15	ARHGEF15	20084	-0.15	0.073	NO
30	PRKCA	PRKCA	PRKCA	20209	-0.16	0.12	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 ERK PATHWAY.

Figure S24. 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 GSK3 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NGFR	NGFR	NGFR	93	0.69	0.18	YES
2	GNGT1	GNGT1	GNGT1	232	0.59	0.33	YES
3	NGF	NGF	NGF	366	0.54	0.47	YES
4	EGFR	EGFR	EGFR	2227	0.28	0.46	YES
5	IGF1R	IGF1R	IGF1R	2765	0.24	0.5	YES
6	RPS6KA5	RPS6KA5	RPS6KA5	6141	0.11	0.38	NO
7	SHC1	SHC1	SHC1	7756	0.082	0.33	NO
8	MYC	MYC	MYC	8027	0.078	0.34	NO
9	MKNK1	MKNK1	MKNK1	8349	0.074	0.35	NO
10	GNAS	GNAS	GNAS	8608	0.07	0.36	NO
11	MAPK1	MAPK1	MAPK1	9913	0.053	0.31	NO
12	ITGB1	ITGB1	ITGB1	10591	0.045	0.3	NO
13	MKNK2	MKNK2	MKNK2	10948	0.041	0.29	NO
14	GNB1	GNB1	GNB1	11013	0.04	0.3	NO
15	SOS1	SOS1	SOS1	11312	0.037	0.3	NO
16	MAP2K1	MAP2K1	MAP2K1	11573	0.033	0.29	NO
17	MAP2K2	MAP2K2	MAP2K2	12740	0.02	0.25	NO
18	ELK1	ELK1	ELK1	13207	0.014	0.23	NO
19	STAT3	STAT3	STAT3	14514	-0.0015	0.17	NO
20	GRB2	GRB2	GRB2	14676	-0.0035	0.17	NO
21	PDGFRA	PDGFRA	PDGFRA	15215	-0.011	0.15	NO
22	RPS6KA1	RPS6KA1	RPS6KA1	15937	-0.022	0.12	NO
23	RAF1	RAF1	RAF1	16087	-0.024	0.12	NO
24	SRC	SRC	SRC	18753	-0.09	0.028	NO
25	MAPK3	MAPK3	MAPK3	19738	-0.13	0.019	NO
26	PTPRR	PTPRR	PTPRR	22154	-0.44	0.03	NO

Figure S25. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA GSK3 PATHWAY.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA GSK3 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA INTEGRIN PATHWAY

Table 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	PITX2	PITX2	PITX2	108	0.67	0.046	YES
2	WNT9A	WNT9A	WNT9A	213	0.6	0.087	YES
3	WNT7A	WNT7A	WNT7A	289	0.56	0.13	YES
4	WNT7B	WNT7B	WNT7B	498	0.5	0.16	YES
5	PYGO1	PYGO1	PYGO1	687	0.46	0.18	YES
6	WNT6	WNT6	WNT6	723	0.45	0.21	YES
7	FOXN1	FOXN1	FOXN1	1021	0.41	0.23	YES
8	SFRP4	SFRP4	SFRP4	1059	0.4	0.26	YES
9	SFRP1	SFRP1	SFRP1	1214	0.38	0.28	YES
10	TCF7L1	TCF7L1	TCF7L1	1274	0.37	0.31	YES
11	WNT2B	WNT2B	WNT2B	1430	0.35	0.33	YES
12	WISP1	WISP1	WISP1	1852	0.31	0.33	YES
13	WNT10A	WNT10A	WNT10A	1916	0.3	0.35	YES
14	T	T	T	1959	0.3	0.37	YES
15	FZD7	FZD7	FZD7	2024	0.3	0.39	YES
16	FZD6	FZD6	FZD6	2038	0.3	0.42	YES
17	WNT2	WNT2	WNT2	2116	0.29	0.43	YES
18	WNT3	WNT3	WNT3	2185	0.28	0.45	YES
19	FZD1	FZD1	FZD1	2649	0.25	0.45	YES
20	KREMEN1	KREMEN1	KREMEN1	2982	0.23	0.45	YES
21	FZD2	FZD2	FZD2	3153	0.22	0.46	YES
22	LEF1	LEF1	LEF1	3492	0.2	0.46	YES
23	DVL2	DVL2	DVL2	3580	0.2	0.47	YES
24	WNT5B	WNT5B	WNT5B	3955	0.18	0.47	YES
25	WNT5A	WNT5A	WNT5A	4096	0.18	0.48	YES
26	NKD1	NKD1	NKD1	4124	0.18	0.49	YES
27	DKK1	DKK1	DKK1	4435	0.16	0.49	NO
28	WNT4	WNT4	WNT4	4890	0.15	0.48	NO
29	FZD8	FZD8	FZD8	5468	0.13	0.46	NO
30	WIF1	WIF1	WIF1	6023	0.12	0.45	NO
31	WNT16	WNT16	WNT16	6044	0.12	0.46	NO
32	CCND1	CCND1	CCND1	6048	0.12	0.47	NO
33	HPRT1	HPRT1	HPRT1	6155	0.11	0.47	NO
34	CTNNBIP1	CTNNBIP1	CTNNBIP1	6217	0.11	0.48	NO
35	SENP2	SENP2	SENP2	6327	0.11	0.48	NO
36	PORCN	PORCN	PORCN	6717	0.1	0.47	NO
37	GAPDH	GAPDH	GAPDH	6898	0.097	0.47	NO
38	GSK3B	GSK3B	GSK3B	7774	0.082	0.44	NO
39	MYC	MYC	MYC	8027	0.078	0.43	NO
40	JUN	JUN	JUN	8055	0.078	0.44	NO
41	DIXDC1	DIXDC1	DIXDC1	8083	0.077	0.44	NO
42	CSNK1A1	CSNK1A1	CSNK1A1	8252	0.075	0.44	NO
43	FBXW4	FBXW4	FBXW4	8398	0.073	0.44	NO
44	FOSL1	FOSL1	FOSL1	8680	0.068	0.43	NO
45	DAAM1	DAAM1	DAAM1	8826	0.066	0.43	NO
46	CSNK1G1	CSNK1G1	CSNK1G1	9003	0.064	0.43	NO
47	FBXW2	FBXW2	FBXW2	9302	0.06	0.42	NO
48	FZD3	FZD3	FZD3	10803	0.042	0.36	NO
49	AXIN1	AXIN1	AXIN1	11300	0.037	0.34	NO
50	AES	AES	AES	11519	0.034	0.33	NO
51	WNT11	WNT11	WNT11	11762	0.031	0.32	NO
52	EP300	EP300	EP300	11787	0.031	0.32	NO
53	CSNK2A1	CSNK2A1	CSNK2A1	12610	0.021	0.29	NO
54	ACTB	ACTB	ACTB	12925	0.018	0.28	NO
55	BTRC	BTRC	BTRC	13008	0.017	0.27	NO
56	APC	APC	APC	13182	0.015	0.27	NO
57	FBXW11	FBXW11	FBXW11	14152	0.0033	0.22	NO
58	CTBP1	CTBP1	CTBP1	14396	0.000031	0.21	NO
59	DVL1	DVL1	DVL1	14489	-0.0012	0.21	NO
60	B2M	B2M	B2M	14621	-0.0028	0.2	NO
61	BCL9	BCL9	BCL9	14742	-0.0042	0.2	NO
62	GSK3A	GSK3A	GSK3A	14895	-0.0065	0.19	NO
63	TLE2	TLE2	TLE2	15074	-0.0089	0.19	NO
64	PPP2R1A	PPP2R1A	PPP2R1A	15096	-0.0092	0.18	NO
65	CTNNB1	CTNNB1	CTNNB1	15609	-0.017	0.16	NO
66	SLC9A3R1	SLC9A3R1	SLC9A3R1	15947	-0.022	0.15	NO
67	LRP6	LRP6	LRP6	16122	-0.025	0.14	NO
68	CSNK1D	CSNK1D	CSNK1D	16357	-0.029	0.14	NO
69	RPL13A	RPL13A	RPL13A	16439	-0.03	0.14	NO
70	CXXC4	CXXC4	CXXC4	17112	-0.044	0.11	NO
71	CCND3	CCND3	CCND3	17586	-0.055	0.093	NO
72	LRP5	LRP5	LRP5	17703	-0.057	0.092	NO
73	NLK	NLK	NLK	17826	-0.06	0.092	NO
74	TLE1	TLE1	TLE1	18016	-0.066	0.088	NO
75	FGF4	FGF4	FGF4	18285	-0.074	0.082	NO
76	TCF7	TCF7	TCF7	18503	-0.08	0.079	NO
77	SOX17	SOX17	SOX17	18649	-0.086	0.079	NO
78	FZD4	FZD4	FZD4	18771	-0.09	0.08	NO
79	CTBP2	CTBP2	CTBP2	18782	-0.091	0.087	NO
80	CCND2	CCND2	CCND2	18846	-0.093	0.091	NO
81	FRAT1	FRAT1	FRAT1	19382	-0.11	0.076	NO
82	WNT1	WNT1	WNT1	19947	-0.14	0.062	NO
83	FRZB	FRZB	FRZB	20447	-0.18	0.053	NO
84	RHOU	RHOU	RHOU	21605	-0.3	0.026	NO
85	FZD5	FZD5	FZD5	21962	-0.38	0.039	NO

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

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

genes ES table in pathway: BIOCARTA MYOSIN PATHWAY

Table 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	WNT3A	WNT3A	WNT3A	7	0.9	0.045	YES
2	CALML3	CALML3	CALML3	145	0.64	0.071	YES
3	WNT9A	WNT9A	WNT9A	213	0.6	0.098	YES
4	WNT7A	WNT7A	WNT7A	289	0.56	0.12	YES
5	FZD9	FZD9	FZD9	296	0.56	0.15	YES
6	POMC	POMC	POMC	300	0.56	0.18	YES
7	FZD10	FZD10	FZD10	349	0.54	0.2	YES
8	ADCY8	ADCY8	ADCY8	469	0.51	0.22	YES
9	WNT7B	WNT7B	WNT7B	498	0.5	0.25	YES
10	WNT10B	WNT10B	WNT10B	626	0.47	0.26	YES
11	WNT6	WNT6	WNT6	723	0.45	0.28	YES
12	CAMK2B	CAMK2B	CAMK2B	732	0.45	0.31	YES
13	ADCY2	ADCY2	ADCY2	1016	0.41	0.31	YES
14	CALML5	CALML5	CALML5	1188	0.38	0.32	YES
15	TCF7L1	TCF7L1	TCF7L1	1274	0.37	0.34	YES
16	WNT2B	WNT2B	WNT2B	1430	0.35	0.35	YES
17	GNAI1	GNAI1	GNAI1	1433	0.35	0.37	YES
18	CAMK2A	CAMK2A	CAMK2A	1743	0.32	0.37	YES
19	WNT10A	WNT10A	WNT10A	1916	0.3	0.38	YES
20	FZD7	FZD7	FZD7	2024	0.3	0.39	YES
21	FZD6	FZD6	FZD6	2038	0.3	0.4	YES
22	WNT2	WNT2	WNT2	2116	0.29	0.41	YES
23	TYR	TYR	TYR	2138	0.29	0.43	YES
24	WNT3	WNT3	WNT3	2185	0.28	0.44	YES
25	GNAO1	GNAO1	GNAO1	2462	0.26	0.44	YES
26	TYRP1	TYRP1	TYRP1	2488	0.26	0.45	YES
27	DCT	DCT	DCT	2527	0.26	0.46	YES
28	FZD1	FZD1	FZD1	2649	0.25	0.47	YES
29	FZD2	FZD2	FZD2	3153	0.22	0.46	YES
30	CALML6	CALML6	CALML6	3337	0.21	0.46	YES
31	LEF1	LEF1	LEF1	3492	0.2	0.46	YES
32	DVL2	DVL2	DVL2	3580	0.2	0.47	YES
33	WNT5B	WNT5B	WNT5B	3955	0.18	0.46	YES
34	WNT5A	WNT5A	WNT5A	4096	0.18	0.47	YES
35	ADCY1	ADCY1	ADCY1	4170	0.17	0.47	YES
36	HRAS	HRAS	HRAS	4586	0.16	0.46	NO
37	WNT4	WNT4	WNT4	4890	0.15	0.46	NO
38	ADCY5	ADCY5	ADCY5	4942	0.15	0.46	NO
39	DVL3	DVL3	DVL3	5016	0.14	0.46	NO
40	PRKX	PRKX	PRKX	5234	0.14	0.46	NO
41	FZD8	FZD8	FZD8	5468	0.13	0.46	NO
42	WNT16	WNT16	WNT16	6044	0.12	0.44	NO
43	PRKACB	PRKACB	PRKACB	6072	0.11	0.44	NO
44	MITF	MITF	MITF	6594	0.1	0.42	NO
45	GSK3B	GSK3B	GSK3B	7774	0.082	0.38	NO
46	ADCY7	ADCY7	ADCY7	7810	0.082	0.38	NO
47	PRKACA	PRKACA	PRKACA	8366	0.073	0.36	NO
48	GNAS	GNAS	GNAS	8608	0.07	0.35	NO
49	CREB1	CREB1	CREB1	9320	0.06	0.32	NO
50	ASIP	ASIP	ASIP	9656	0.056	0.31	NO
51	KIT	KIT	KIT	9747	0.055	0.31	NO
52	MAPK1	MAPK1	MAPK1	9913	0.053	0.31	NO
53	CREBBP	CREBBP	CREBBP	9959	0.052	0.31	NO
54	ADCY9	ADCY9	ADCY9	10176	0.05	0.3	NO
55	GNAI2	GNAI2	GNAI2	10239	0.049	0.3	NO
56	GNAI3	GNAI3	GNAI3	10797	0.042	0.28	NO
57	FZD3	FZD3	FZD3	10803	0.042	0.28	NO
58	KITLG	KITLG	KITLG	11244	0.038	0.26	NO
59	MAP2K1	MAP2K1	MAP2K1	11573	0.033	0.25	NO
60	WNT11	WNT11	WNT11	11762	0.031	0.24	NO
61	EP300	EP300	EP300	11787	0.031	0.24	NO
62	MAP2K2	MAP2K2	MAP2K2	12740	0.02	0.2	NO
63	WNT9B	WNT9B	WNT9B	12808	0.019	0.2	NO
64	NRAS	NRAS	NRAS	13424	0.012	0.17	NO
65	CAMK2G	CAMK2G	CAMK2G	13717	0.0086	0.16	NO
66	CAMK2D	CAMK2D	CAMK2D	13897	0.0063	0.15	NO
67	CALM1	CALM1	CALM1	13930	0.0058	0.15	NO
68	PLCB1	PLCB1	PLCB1	14091	0.0039	0.14	NO
69	PLCB2	PLCB2	PLCB2	14435	-0.00043	0.13	NO
70	DVL1	DVL1	DVL1	14489	-0.0012	0.13	NO
71	CALM2	CALM2	CALM2	14661	-0.0032	0.12	NO
72	CREB3L2	CREB3L2	CREB3L2	15534	-0.016	0.083	NO
73	CTNNB1	CTNNB1	CTNNB1	15609	-0.017	0.081	NO
74	CREB3	CREB3	CREB3	15647	-0.018	0.08	NO
75	PRKCB	PRKCB	PRKCB	15728	-0.019	0.077	NO
76	RAF1	RAF1	RAF1	16087	-0.024	0.063	NO
77	CREB3L4	CREB3L4	CREB3L4	16742	-0.036	0.036	NO
78	GNAQ	GNAQ	GNAQ	16993	-0.041	0.027	NO
79	KRAS	KRAS	KRAS	17433	-0.051	0.01	NO
80	PLCB3	PLCB3	PLCB3	17598	-0.055	0.0057	NO
81	CALM3	CALM3	CALM3	18462	-0.079	-0.028	NO
82	TCF7	TCF7	TCF7	18503	-0.08	-0.026	NO
83	EDN1	EDN1	EDN1	18662	-0.086	-0.029	NO
84	FZD4	FZD4	FZD4	18771	-0.09	-0.029	NO
85	ADCY4	ADCY4	ADCY4	19728	-0.13	-0.064	NO
86	MAPK3	MAPK3	MAPK3	19738	-0.13	-0.058	NO
87	WNT8B	WNT8B	WNT8B	19793	-0.13	-0.054	NO
88	TCF7L2	TCF7L2	TCF7L2	19868	-0.14	-0.05	NO
89	WNT1	WNT1	WNT1	19947	-0.14	-0.047	NO
90	PRKCA	PRKCA	PRKCA	20209	-0.16	-0.05	NO
91	PLCB4	PLCB4	PLCB4	20795	-0.2	-0.066	NO
92	EDNRB	EDNRB	EDNRB	21063	-0.23	-0.066	NO
93	ADCY6	ADCY6	ADCY6	21171	-0.24	-0.059	NO
94	FZD5	FZD5	FZD5	21962	-0.38	-0.074	NO
95	CREB3L1	CREB3L1	CREB3L1	21999	-0.39	-0.056	NO
96	PRKACG	PRKACG	PRKACG	22333	-0.52	-0.045	NO
97	PRKCG	PRKCG	PRKCG	22360	-0.53	-0.02	NO
98	CREB3L3	CREB3L3	CREB3L3	22706	-0.83	0.0063	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: BIOCARTA MYOSIN PATHWAY.

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

genes ES table in pathway: KEGG RNA 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	CALML3	CALML3	CALML3	145	0.64	0.046	YES
2	FBXO43	FBXO43	FBXO43	376	0.54	0.079	YES
3	CPEB1	CPEB1	CPEB1	424	0.52	0.12	YES
4	ADCY8	ADCY8	ADCY8	469	0.51	0.16	YES
5	CAMK2B	CAMK2B	CAMK2B	732	0.45	0.18	YES
6	ADCY2	ADCY2	ADCY2	1016	0.41	0.21	YES
7	CALML5	CALML5	CALML5	1188	0.38	0.23	YES
8	RPS6KA6	RPS6KA6	RPS6KA6	1741	0.32	0.23	YES
9	CAMK2A	CAMK2A	CAMK2A	1743	0.32	0.26	YES
10	MAPK12	MAPK12	MAPK12	2176	0.28	0.26	YES
11	IGF1R	IGF1R	IGF1R	2765	0.24	0.26	YES
12	IGF1	IGF1	IGF1	2973	0.23	0.26	YES
13	PGR	PGR	PGR	3239	0.22	0.27	YES
14	CALML6	CALML6	CALML6	3337	0.21	0.28	YES
15	AR	AR	AR	3711	0.19	0.28	YES
16	ADCY1	ADCY1	ADCY1	4170	0.17	0.28	YES
17	SMC1B	SMC1B	SMC1B	4239	0.17	0.29	YES
18	MAD2L2	MAD2L2	MAD2L2	4621	0.16	0.28	YES
19	ADCY5	ADCY5	ADCY5	4942	0.15	0.28	YES
20	CCNE2	CCNE2	CCNE2	4966	0.14	0.29	YES
21	PKMYT1	PKMYT1	PKMYT1	5030	0.14	0.3	YES
22	PTTG1	PTTG1	PTTG1	5149	0.14	0.31	YES
23	PRKX	PRKX	PRKX	5234	0.14	0.31	YES
24	ANAPC10	ANAPC10	ANAPC10	5924	0.12	0.29	YES
25	STAG3	STAG3	STAG3	6038	0.12	0.3	YES
26	PRKACB	PRKACB	PRKACB	6072	0.11	0.31	YES
27	FBXO5	FBXO5	FBXO5	6226	0.11	0.31	YES
28	CCNB1	CCNB1	CCNB1	6371	0.11	0.31	YES
29	CDK2	CDK2	CDK2	6465	0.1	0.32	YES
30	YWHAG	YWHAG	YWHAG	6505	0.1	0.32	YES
31	YWHAQ	YWHAQ	YWHAQ	6566	0.1	0.33	YES
32	ANAPC1	ANAPC1	ANAPC1	6748	0.1	0.33	YES
33	RBX1	RBX1	RBX1	6846	0.098	0.33	YES
34	MAD2L1	MAD2L1	MAD2L1	6847	0.098	0.34	YES
35	CDC20	CDC20	CDC20	6941	0.096	0.34	YES
36	SPDYA	SPDYA	SPDYA	7237	0.091	0.34	YES
37	CHP2	CHP2	CHP2	7376	0.089	0.34	YES
38	ANAPC7	ANAPC7	ANAPC7	7484	0.087	0.34	YES
39	CCNB2	CCNB2	CCNB2	7523	0.086	0.35	YES
40	CDK1	CDK1	CDK1	7605	0.085	0.35	YES
41	YWHAE	YWHAE	YWHAE	7781	0.082	0.35	YES
42	ADCY7	ADCY7	ADCY7	7810	0.082	0.35	YES
43	PPP1CB	PPP1CB	PPP1CB	7968	0.079	0.35	YES
44	CDC27	CDC27	CDC27	7973	0.079	0.36	YES
45	CUL1	CUL1	CUL1	8133	0.077	0.36	YES
46	CDC23	CDC23	CDC23	8160	0.076	0.36	YES
47	PRKACA	PRKACA	PRKACA	8366	0.073	0.36	NO
48	PPP2R5E	PPP2R5E	PPP2R5E	8889	0.066	0.34	NO
49	BUB1	BUB1	BUB1	9184	0.062	0.34	NO
50	SMC3	SMC3	SMC3	9704	0.056	0.32	NO
51	ITPR1	ITPR1	ITPR1	9725	0.055	0.32	NO
52	MAPK1	MAPK1	MAPK1	9913	0.053	0.32	NO
53	ANAPC4	ANAPC4	ANAPC4	9988	0.052	0.32	NO
54	CDC25C	CDC25C	CDC25C	10005	0.052	0.32	NO
55	PPP3CC	PPP3CC	PPP3CC	10058	0.051	0.32	NO
56	PPP3R1	PPP3R1	PPP3R1	10070	0.051	0.33	NO
57	ANAPC13	ANAPC13	ANAPC13	10085	0.051	0.33	NO
58	ADCY9	ADCY9	ADCY9	10176	0.05	0.33	NO
59	PPP3CB	PPP3CB	PPP3CB	10222	0.049	0.33	NO
60	PLK1	PLK1	PLK1	10228	0.049	0.34	NO
61	SKP1	SKP1	SKP1	10314	0.048	0.34	NO
62	PPP2R5C	PPP2R5C	PPP2R5C	10570	0.045	0.33	NO
63	YWHAH	YWHAH	YWHAH	10674	0.044	0.33	NO
64	ESPL1	ESPL1	ESPL1	11449	0.035	0.3	NO
65	ANAPC5	ANAPC5	ANAPC5	11455	0.035	0.3	NO
66	MAP2K1	MAP2K1	MAP2K1	11573	0.033	0.3	NO
67	YWHAZ	YWHAZ	YWHAZ	11670	0.032	0.3	NO
68	PPP3R2	PPP3R2	PPP3R2	12209	0.026	0.27	NO
69	ANAPC2	ANAPC2	ANAPC2	12304	0.025	0.27	NO
70	PPP2R5B	PPP2R5B	PPP2R5B	12359	0.024	0.27	NO
71	ANAPC11	ANAPC11	ANAPC11	12365	0.024	0.27	NO
72	SMC1A	SMC1A	SMC1A	12439	0.023	0.27	NO
73	PPP2R5D	PPP2R5D	PPP2R5D	12471	0.023	0.27	NO
74	PPP1CC	PPP1CC	PPP1CC	12476	0.023	0.27	NO
75	BTRC	BTRC	BTRC	13008	0.017	0.25	NO
76	PPP1CA	PPP1CA	PPP1CA	13093	0.016	0.25	NO
77	PPP3CA	PPP3CA	PPP3CA	13469	0.011	0.23	NO
78	CAMK2G	CAMK2G	CAMK2G	13717	0.0086	0.22	NO
79	CAMK2D	CAMK2D	CAMK2D	13897	0.0063	0.22	NO
80	CALM1	CALM1	CALM1	13930	0.0058	0.22	NO
81	PPP2CB	PPP2CB	PPP2CB	14098	0.0038	0.21	NO
82	FBXW11	FBXW11	FBXW11	14152	0.0033	0.21	NO
83	SGOL1	SGOL1	SGOL1	14574	-0.0021	0.19	NO
84	CALM2	CALM2	CALM2	14661	-0.0032	0.18	NO
85	AURKA	AURKA	AURKA	14834	-0.0056	0.18	NO
86	PPP2R1A	PPP2R1A	PPP2R1A	15096	-0.0092	0.17	NO
87	CDC16	CDC16	CDC16	15163	-0.01	0.16	NO
88	PLCZ1	PLCZ1	PLCZ1	15236	-0.011	0.16	NO
89	PPP2R5A	PPP2R5A	PPP2R5A	15773	-0.02	0.14	NO
90	CDC26	CDC26	CDC26	15886	-0.021	0.14	NO
91	YWHAB	YWHAB	YWHAB	15913	-0.021	0.14	NO
92	RPS6KA1	RPS6KA1	RPS6KA1	15937	-0.022	0.14	NO
93	SLK	SLK	SLK	16965	-0.041	0.097	NO
94	ITPR3	ITPR3	ITPR3	17243	-0.047	0.088	NO
95	REC8	REC8	REC8	17408	-0.05	0.085	NO
96	CCNE1	CCNE1	CCNE1	18220	-0.072	0.055	NO
97	CALM3	CALM3	CALM3	18462	-0.079	0.051	NO
98	PTTG2	PTTG2	PTTG2	18497	-0.08	0.056	NO
99	ITPR2	ITPR2	ITPR2	18500	-0.08	0.063	NO
100	RPS6KA2	RPS6KA2	RPS6KA2	18604	-0.084	0.065	NO
101	PPP2R1B	PPP2R1B	PPP2R1B	18796	-0.091	0.064	NO
102	RPS6KA3	RPS6KA3	RPS6KA3	18987	-0.099	0.064	NO
103	ADCY4	ADCY4	ADCY4	19728	-0.13	0.042	NO
104	MAPK3	MAPK3	MAPK3	19738	-0.13	0.052	NO
105	ADCY6	ADCY6	ADCY6	21171	-0.24	0.0086	NO
106	SPDYC	SPDYC	SPDYC	21490	-0.28	0.018	NO
107	PRKACG	PRKACG	PRKACG	22333	-0.52	0.023	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 RNA DEGRADATION.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RNA 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 CELL CYCLE

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	COL11A1	COL11A1	COL11A1	62	0.74	0.026	YES
2	COL4A6	COL4A6	COL4A6	90	0.69	0.051	YES
3	ITGA2B	ITGA2B	ITGA2B	396	0.53	0.058	YES
4	COL6A6	COL6A6	COL6A6	450	0.52	0.076	YES
5	TNC	TNC	TNC	541	0.49	0.09	YES
6	LAMA1	LAMA1	LAMA1	573	0.48	0.11	YES
7	SPP1	SPP1	SPP1	676	0.46	0.12	YES
8	COL2A1	COL2A1	COL2A1	772	0.45	0.13	YES
9	EGF	EGF	EGF	851	0.43	0.15	YES
10	THBS4	THBS4	THBS4	857	0.43	0.16	YES
11	MAPK10	MAPK10	MAPK10	1168	0.38	0.16	YES
12	PAK7	PAK7	PAK7	1181	0.38	0.18	YES
13	MYL7	MYL7	MYL7	1305	0.36	0.19	YES
14	RELN	RELN	RELN	1394	0.36	0.2	YES
15	ACTN2	ACTN2	ACTN2	1571	0.34	0.2	YES
16	ACTN3	ACTN3	ACTN3	1697	0.32	0.21	YES
17	CAV1	CAV1	CAV1	1786	0.32	0.22	YES
18	ITGA11	ITGA11	ITGA11	2001	0.3	0.22	YES
19	TNN	TNN	TNN	2071	0.29	0.23	YES
20	CAV2	CAV2	CAV2	2178	0.28	0.23	YES
21	FN1	FN1	FN1	2200	0.28	0.24	YES
22	EGFR	EGFR	EGFR	2227	0.28	0.25	YES
23	AKT3	AKT3	AKT3	2236	0.28	0.26	YES
24	VEGFC	VEGFC	VEGFC	2268	0.28	0.27	YES
25	PDGFC	PDGFC	PDGFC	2283	0.27	0.28	YES
26	MYLK	MYLK	MYLK	2290	0.27	0.29	YES
27	COL5A1	COL5A1	COL5A1	2403	0.26	0.3	YES
28	THBS2	THBS2	THBS2	2510	0.26	0.3	YES
29	VAV3	VAV3	VAV3	2531	0.26	0.31	YES
30	RAC3	RAC3	RAC3	2762	0.24	0.31	YES
31	IGF1R	IGF1R	IGF1R	2765	0.24	0.32	YES
32	COL5A3	COL5A3	COL5A3	2768	0.24	0.33	YES
33	COL6A2	COL6A2	COL6A2	2844	0.24	0.34	YES
34	COL1A1	COL1A1	COL1A1	2850	0.24	0.34	YES
35	COL1A2	COL1A2	COL1A2	2938	0.23	0.35	YES
36	IGF1	IGF1	IGF1	2973	0.23	0.36	YES
37	FLNA	FLNA	FLNA	2977	0.23	0.37	YES
38	COL6A1	COL6A1	COL6A1	3055	0.23	0.37	YES
39	COL3A1	COL3A1	COL3A1	3069	0.22	0.38	YES
40	PIK3CD	PIK3CD	PIK3CD	3268	0.21	0.38	YES
41	MYL9	MYL9	MYL9	3271	0.21	0.39	YES
42	COL5A2	COL5A2	COL5A2	3284	0.21	0.39	YES
43	FIGF	FIGF	FIGF	3313	0.21	0.4	YES
44	SHC4	SHC4	SHC4	3429	0.2	0.4	YES
45	IBSP	IBSP	IBSP	3686	0.19	0.4	YES
46	PGF	PGF	PGF	3701	0.19	0.41	YES
47	COL6A3	COL6A3	COL6A3	3928	0.18	0.4	YES
48	ITGA5	ITGA5	ITGA5	4277	0.17	0.4	YES
49	LAMC2	LAMC2	LAMC2	4441	0.16	0.39	YES
50	BCL2	BCL2	BCL2	4470	0.16	0.4	YES
51	COMP	COMP	COMP	4485	0.16	0.4	YES
52	THBS1	THBS1	THBS1	4546	0.16	0.41	YES
53	FLNC	FLNC	FLNC	4587	0.16	0.41	YES
54	PARVB	PARVB	PARVB	4617	0.16	0.42	YES
55	PAK6	PAK6	PAK6	4627	0.16	0.42	YES
56	PIK3CA	PIK3CA	PIK3CA	4650	0.16	0.43	YES
57	LAMB4	LAMB4	LAMB4	4751	0.15	0.43	YES
58	MYL10	MYL10	MYL10	5204	0.14	0.42	NO
59	ITGB8	ITGB8	ITGB8	5305	0.13	0.42	NO
60	VEGFB	VEGFB	VEGFB	5478	0.13	0.41	NO
61	ACTN1	ACTN1	ACTN1	5480	0.13	0.42	NO
62	ITGAV	ITGAV	ITGAV	5879	0.12	0.4	NO
63	CRKL	CRKL	CRKL	5909	0.12	0.41	NO
64	CCND1	CCND1	CCND1	6048	0.12	0.41	NO
65	LAMA2	LAMA2	LAMA2	6105	0.11	0.41	NO
66	LAMB3	LAMB3	LAMB3	6119	0.11	0.41	NO
67	PDGFRB	PDGFRB	PDGFRB	6266	0.11	0.41	NO
68	PAK2	PAK2	PAK2	6514	0.1	0.4	NO
69	THBS3	THBS3	THBS3	6633	0.1	0.4	NO
70	ITGA4	ITGA4	ITGA4	6945	0.096	0.39	NO
71	ITGA6	ITGA6	ITGA6	6968	0.096	0.39	NO
72	PPP1R12A	PPP1R12A	PPP1R12A	7011	0.095	0.4	NO
73	LAMC1	LAMC1	LAMC1	7059	0.094	0.4	NO
74	SHC3	SHC3	SHC3	7079	0.094	0.4	NO
75	LAMA5	LAMA5	LAMA5	7235	0.091	0.4	NO
76	MYLK3	MYLK3	MYLK3	7352	0.089	0.4	NO
77	ITGB6	ITGB6	ITGB6	7391	0.088	0.4	NO
78	COL4A2	COL4A2	COL4A2	7502	0.087	0.4	NO
79	ITGB5	ITGB5	ITGB5	7576	0.086	0.4	NO
80	SHC1	SHC1	SHC1	7756	0.082	0.39	NO
81	ITGA2	ITGA2	ITGA2	7766	0.082	0.39	NO
82	GSK3B	GSK3B	GSK3B	7774	0.082	0.4	NO
83	RAPGEF1	RAPGEF1	RAPGEF1	7920	0.08	0.39	NO
84	PPP1CB	PPP1CB	PPP1CB	7968	0.079	0.39	NO
85	JUN	JUN	JUN	8055	0.078	0.39	NO
86	COL11A2	COL11A2	COL11A2	8088	0.077	0.4	NO
87	PARVA	PARVA	PARVA	8159	0.076	0.4	NO
88	LAMA3	LAMA3	LAMA3	8239	0.075	0.39	NO
89	RAC2	RAC2	RAC2	8355	0.073	0.39	NO
90	LAMB1	LAMB1	LAMB1	8600	0.07	0.38	NO
91	LAMA4	LAMA4	LAMA4	8633	0.069	0.38	NO
92	BRAF	BRAF	BRAF	8799	0.067	0.38	NO
93	ITGA9	ITGA9	ITGA9	8813	0.067	0.38	NO
94	ITGB4	ITGB4	ITGB4	8828	0.066	0.38	NO
95	BAD	BAD	BAD	9013	0.064	0.38	NO
96	PTK2	PTK2	PTK2	9078	0.063	0.38	NO
97	VCL	VCL	VCL	9299	0.06	0.37	NO
98	ZYX	ZYX	ZYX	9567	0.057	0.36	NO
99	PIK3R2	PIK3R2	PIK3R2	9675	0.056	0.36	NO
100	PARVG	PARVG	PARVG	9714	0.056	0.36	NO
101	PIP5K1C	PIP5K1C	PIP5K1C	9762	0.055	0.36	NO
102	MAPK1	MAPK1	MAPK1	9913	0.053	0.35	NO
103	PIK3R1	PIK3R1	PIK3R1	9986	0.052	0.35	NO
104	COL4A1	COL4A1	COL4A1	10380	0.047	0.34	NO
105	ITGB1	ITGB1	ITGB1	10591	0.045	0.33	NO
106	SOS2	SOS2	SOS2	10698	0.044	0.33	NO
107	ITGA3	ITGA3	ITGA3	10715	0.043	0.33	NO
108	TLN1	TLN1	TLN1	10841	0.042	0.32	NO
109	AKT2	AKT2	AKT2	10883	0.042	0.32	NO
110	AKT1	AKT1	AKT1	11073	0.04	0.32	NO
111	PDGFB	PDGFB	PDGFB	11077	0.04	0.32	NO
112	CRK	CRK	CRK	11144	0.039	0.32	NO
113	SOS1	SOS1	SOS1	11312	0.037	0.31	NO
114	DOCK1	DOCK1	DOCK1	11465	0.035	0.31	NO
115	MAP2K1	MAP2K1	MAP2K1	11573	0.033	0.3	NO
116	BIRC2	BIRC2	BIRC2	11630	0.033	0.3	NO
117	RAP1B	RAP1B	RAP1B	11775	0.031	0.3	NO
118	ROCK1	ROCK1	ROCK1	11940	0.029	0.29	NO
119	PTEN	PTEN	PTEN	11941	0.029	0.29	NO
120	PDGFA	PDGFA	PDGFA	11963	0.029	0.29	NO
121	ILK	ILK	ILK	12191	0.026	0.28	NO
122	PPP1CC	PPP1CC	PPP1CC	12476	0.023	0.27	NO
123	VAV2	VAV2	VAV2	12819	0.019	0.26	NO
124	PXN	PXN	PXN	12830	0.019	0.26	NO
125	ACTB	ACTB	ACTB	12925	0.018	0.25	NO
126	LAMB2	LAMB2	LAMB2	12980	0.017	0.25	NO
127	RAP1A	RAP1A	RAP1A	13042	0.016	0.25	NO
128	PPP1CA	PPP1CA	PPP1CA	13093	0.016	0.25	NO
129	MYLK2	MYLK2	MYLK2	13130	0.015	0.25	NO
130	ELK1	ELK1	ELK1	13207	0.014	0.24	NO
131	ITGA1	ITGA1	ITGA1	13315	0.013	0.24	NO
132	CDC42	CDC42	CDC42	13322	0.013	0.24	NO
133	VAV1	VAV1	VAV1	13574	0.01	0.23	NO
134	MYL12A	MYL12A	MYL12A	13837	0.0071	0.22	NO
135	PIK3R5	PIK3R5	PIK3R5	13870	0.0067	0.22	NO
136	SHC2	SHC2	SHC2	14196	0.0026	0.2	NO
137	ACTG1	ACTG1	ACTG1	14279	0.0015	0.2	NO
138	MYL12B	MYL12B	MYL12B	14327	0.00082	0.2	NO
139	ITGB3	ITGB3	ITGB3	14455	-0.0006	0.19	NO
140	MAPK9	MAPK9	MAPK9	14469	-0.00082	0.19	NO
141	GRB2	GRB2	GRB2	14676	-0.0035	0.18	NO
142	ARHGAP5	ARHGAP5	ARHGAP5	14693	-0.0037	0.18	NO
143	PAK1	PAK1	PAK1	14849	-0.0059	0.17	NO
144	FYN	FYN	FYN	14958	-0.0072	0.17	NO
145	CAPN2	CAPN2	CAPN2	15211	-0.011	0.16	NO
146	PDGFRA	PDGFRA	PDGFRA	15215	-0.011	0.16	NO
147	RASGRF1	RASGRF1	RASGRF1	15374	-0.013	0.15	NO
148	PIK3CB	PIK3CB	PIK3CB	15400	-0.014	0.15	NO
149	PAK3	PAK3	PAK3	15555	-0.016	0.15	NO
150	PAK4	PAK4	PAK4	15579	-0.016	0.15	NO
151	MET	MET	MET	15584	-0.017	0.15	NO
152	CTNNB1	CTNNB1	CTNNB1	15609	-0.017	0.15	NO
153	RAC1	RAC1	RAC1	15641	-0.018	0.14	NO
154	FLT4	FLT4	FLT4	15727	-0.019	0.14	NO
155	PRKCB	PRKCB	PRKCB	15728	-0.019	0.14	NO
156	XIAP	XIAP	XIAP	15758	-0.019	0.14	NO
157	RAF1	RAF1	RAF1	16087	-0.024	0.13	NO
158	ITGB7	ITGB7	ITGB7	16105	-0.025	0.13	NO
159	MYLPF	MYLPF	MYLPF	16108	-0.025	0.13	NO
160	PDPK1	PDPK1	PDPK1	16156	-0.026	0.13	NO
161	MAPK8	MAPK8	MAPK8	16187	-0.026	0.13	NO
162	MYL5	MYL5	MYL5	16424	-0.03	0.12	NO
163	MYL2	MYL2	MYL2	16463	-0.031	0.12	NO
164	DIAPH1	DIAPH1	DIAPH1	16703	-0.035	0.11	NO
165	LAMC3	LAMC3	LAMC3	16752	-0.036	0.11	NO
166	ACTN4	ACTN4	ACTN4	16760	-0.036	0.11	NO
167	PIK3R3	PIK3R3	PIK3R3	17278	-0.048	0.089	NO
168	RHOA	RHOA	RHOA	17320	-0.048	0.089	NO
169	ROCK2	ROCK2	ROCK2	17327	-0.049	0.091	NO
170	FLNB	FLNB	FLNB	17400	-0.05	0.089	NO
171	BCAR1	BCAR1	BCAR1	17405	-0.05	0.091	NO
172	CAV3	CAV3	CAV3	17545	-0.054	0.087	NO
173	CCND3	CCND3	CCND3	17586	-0.055	0.087	NO
174	ITGA7	ITGA7	ITGA7	17913	-0.063	0.076	NO
175	TNR	TNR	TNR	18240	-0.073	0.064	NO
176	FLT1	FLT1	FLT1	18544	-0.082	0.054	NO
177	ITGA10	ITGA10	ITGA10	18676	-0.087	0.051	NO
178	SRC	SRC	SRC	18753	-0.09	0.051	NO
179	CCND2	CCND2	CCND2	18846	-0.093	0.051	NO
180	VEGFA	VEGFA	VEGFA	18915	-0.096	0.052	NO
181	TNXB	TNXB	TNXB	18978	-0.098	0.052	NO
182	VASP	VASP	VASP	19105	-0.1	0.051	NO
183	COL4A4	COL4A4	COL4A4	19248	-0.11	0.049	NO
184	KDR	KDR	KDR	19406	-0.12	0.046	NO
185	VWF	VWF	VWF	19583	-0.12	0.043	NO
186	TLN2	TLN2	TLN2	19721	-0.13	0.042	NO
187	MAPK3	MAPK3	MAPK3	19738	-0.13	0.046	NO
188	HGF	HGF	HGF	19754	-0.13	0.051	NO
189	PIK3CG	PIK3CG	PIK3CG	19851	-0.14	0.052	NO
190	PRKCA	PRKCA	PRKCA	20209	-0.16	0.042	NO
191	ITGA8	ITGA8	ITGA8	20248	-0.16	0.047	NO
192	PDGFD	PDGFD	PDGFD	20335	-0.17	0.049	NO
193	CHAD	CHAD	CHAD	20537	-0.18	0.047	NO
194	ERBB2	ERBB2	ERBB2	21099	-0.23	0.032	NO
195	BIRC3	BIRC3	BIRC3	21592	-0.3	0.022	NO
196	VTN	VTN	VTN	21825	-0.35	0.025	NO
197	PRKCG	PRKCG	PRKCG	22360	-0.53	0.022	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 CELL CYCLE.

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

genes ES table in pathway: KEGG OOCYTE MEIOSIS

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	WNT3A	WNT3A	WNT3A	7	0.9	0.04	YES
2	SFRP2	SFRP2	SFRP2	157	0.63	0.062	YES
3	WNT9A	WNT9A	WNT9A	213	0.6	0.086	YES
4	WNT7A	WNT7A	WNT7A	289	0.56	0.11	YES
5	FZD9	FZD9	FZD9	296	0.56	0.13	YES
6	FZD10	FZD10	FZD10	349	0.54	0.16	YES
7	VANGL2	VANGL2	VANGL2	485	0.5	0.17	YES
8	WNT7B	WNT7B	WNT7B	498	0.5	0.19	YES
9	PRICKLE1	PRICKLE1	PRICKLE1	618	0.47	0.21	YES
10	WNT10B	WNT10B	WNT10B	626	0.47	0.23	YES
11	WNT6	WNT6	WNT6	723	0.45	0.25	YES
12	CAMK2B	CAMK2B	CAMK2B	732	0.45	0.27	YES
13	SFRP4	SFRP4	SFRP4	1059	0.4	0.27	YES
14	MAPK10	MAPK10	MAPK10	1168	0.38	0.28	YES
15	SFRP1	SFRP1	SFRP1	1214	0.38	0.3	YES
16	TCF7L1	TCF7L1	TCF7L1	1274	0.37	0.31	YES
17	WNT2B	WNT2B	WNT2B	1430	0.35	0.32	YES
18	CAMK2A	CAMK2A	CAMK2A	1743	0.32	0.32	YES
19	WNT10A	WNT10A	WNT10A	1916	0.3	0.33	YES
20	FZD7	FZD7	FZD7	2024	0.3	0.34	YES
21	FZD6	FZD6	FZD6	2038	0.3	0.35	YES
22	WNT2	WNT2	WNT2	2116	0.29	0.36	YES
23	WNT3	WNT3	WNT3	2185	0.28	0.37	YES
24	NKD2	NKD2	NKD2	2202	0.28	0.38	YES
25	FZD1	FZD1	FZD1	2649	0.25	0.37	YES
26	RAC3	RAC3	RAC3	2762	0.24	0.38	YES
27	FZD2	FZD2	FZD2	3153	0.22	0.37	YES
28	LEF1	LEF1	LEF1	3492	0.2	0.36	YES
29	DVL2	DVL2	DVL2	3580	0.2	0.37	YES
30	TBL1Y	TBL1Y	TBL1Y	3856	0.19	0.36	YES
31	WNT5B	WNT5B	WNT5B	3955	0.18	0.37	YES
32	WNT5A	WNT5A	WNT5A	4096	0.18	0.37	YES
33	NKD1	NKD1	NKD1	4124	0.18	0.38	YES
34	DKK2	DKK2	DKK2	4149	0.17	0.38	YES
35	CSNK1A1L	CSNK1A1L	CSNK1A1L	4210	0.17	0.39	YES
36	DKK1	DKK1	DKK1	4435	0.16	0.38	YES
37	NFATC1	NFATC1	NFATC1	4630	0.16	0.38	YES
38	PRICKLE2	PRICKLE2	PRICKLE2	4633	0.16	0.39	YES
39	WNT4	WNT4	WNT4	4890	0.15	0.39	YES
40	DVL3	DVL3	DVL3	5016	0.14	0.39	YES
41	DAAM2	DAAM2	DAAM2	5190	0.14	0.38	YES
42	PRKX	PRKX	PRKX	5234	0.14	0.39	YES
43	FZD8	FZD8	FZD8	5468	0.13	0.38	YES
44	NFATC4	NFATC4	NFATC4	5539	0.13	0.39	YES
45	APC2	APC2	APC2	5870	0.12	0.38	YES
46	SIAH1	SIAH1	SIAH1	5936	0.12	0.38	YES
47	WIF1	WIF1	WIF1	6023	0.12	0.38	YES
48	WNT16	WNT16	WNT16	6044	0.12	0.39	YES
49	CCND1	CCND1	CCND1	6048	0.12	0.39	YES
50	PRKACB	PRKACB	PRKACB	6072	0.11	0.4	YES
51	CTNNBIP1	CTNNBIP1	CTNNBIP1	6217	0.11	0.39	YES
52	SENP2	SENP2	SENP2	6327	0.11	0.39	YES
53	CSNK2A2	CSNK2A2	CSNK2A2	6595	0.1	0.39	YES
54	TBL1XR1	TBL1XR1	TBL1XR1	6604	0.1	0.39	YES
55	SMAD2	SMAD2	SMAD2	6645	0.1	0.39	YES
56	TBL1X	TBL1X	TBL1X	6650	0.1	0.4	YES
57	TP53	TP53	TP53	6654	0.1	0.4	YES
58	PORCN	PORCN	PORCN	6717	0.1	0.4	YES
59	RBX1	RBX1	RBX1	6846	0.098	0.4	NO
60	CHP2	CHP2	CHP2	7376	0.089	0.38	NO
61	RUVBL1	RUVBL1	RUVBL1	7429	0.088	0.39	NO
62	SMAD4	SMAD4	SMAD4	7758	0.082	0.38	NO
63	GSK3B	GSK3B	GSK3B	7774	0.082	0.38	NO
64	VANGL1	VANGL1	VANGL1	7971	0.079	0.37	NO
65	MYC	MYC	MYC	8027	0.078	0.37	NO
66	JUN	JUN	JUN	8055	0.078	0.38	NO
67	CUL1	CUL1	CUL1	8133	0.077	0.38	NO
68	CSNK1A1	CSNK1A1	CSNK1A1	8252	0.075	0.37	NO
69	NFATC3	NFATC3	NFATC3	8328	0.074	0.37	NO
70	RAC2	RAC2	RAC2	8355	0.073	0.38	NO
71	PRKACA	PRKACA	PRKACA	8366	0.073	0.38	NO
72	CSNK1E	CSNK1E	CSNK1E	8566	0.07	0.37	NO
73	FOSL1	FOSL1	FOSL1	8680	0.068	0.37	NO
74	DAAM1	DAAM1	DAAM1	8826	0.066	0.37	NO
75	PPP2R5E	PPP2R5E	PPP2R5E	8889	0.066	0.37	NO
76	SMAD3	SMAD3	SMAD3	9093	0.063	0.36	NO
77	CHD8	CHD8	CHD8	9636	0.056	0.34	NO
78	CACYBP	CACYBP	CACYBP	9711	0.056	0.34	NO
79	CREBBP	CREBBP	CREBBP	9959	0.052	0.33	NO
80	PPP3CC	PPP3CC	PPP3CC	10058	0.051	0.33	NO
81	PPP3R1	PPP3R1	PPP3R1	10070	0.051	0.33	NO
82	PPP3CB	PPP3CB	PPP3CB	10222	0.049	0.33	NO
83	SKP1	SKP1	SKP1	10314	0.048	0.32	NO
84	PPP2R5C	PPP2R5C	PPP2R5C	10570	0.045	0.32	NO
85	NFAT5	NFAT5	NFAT5	10794	0.042	0.31	NO
86	FZD3	FZD3	FZD3	10803	0.042	0.31	NO
87	MAP3K7	MAP3K7	MAP3K7	11053	0.04	0.3	NO
88	AXIN1	AXIN1	AXIN1	11300	0.037	0.29	NO
89	WNT11	WNT11	WNT11	11762	0.031	0.27	NO
90	EP300	EP300	EP300	11787	0.031	0.27	NO
91	ROCK1	ROCK1	ROCK1	11940	0.029	0.27	NO
92	PPP3R2	PPP3R2	PPP3R2	12209	0.026	0.26	NO
93	PPP2R5D	PPP2R5D	PPP2R5D	12471	0.023	0.25	NO
94	CSNK2A1	CSNK2A1	CSNK2A1	12610	0.021	0.24	NO
95	WNT9B	WNT9B	WNT9B	12808	0.019	0.23	NO
96	BTRC	BTRC	BTRC	13008	0.017	0.22	NO
97	APC	APC	APC	13182	0.015	0.22	NO
98	PPARD	PPARD	PPARD	13198	0.014	0.22	NO
99	SFRP5	SFRP5	SFRP5	13218	0.014	0.22	NO
100	PPP3CA	PPP3CA	PPP3CA	13469	0.011	0.21	NO
101	CAMK2G	CAMK2G	CAMK2G	13717	0.0086	0.2	NO
102	CAMK2D	CAMK2D	CAMK2D	13897	0.0063	0.19	NO
103	PLCB1	PLCB1	PLCB1	14091	0.0039	0.18	NO
104	PPP2CB	PPP2CB	PPP2CB	14098	0.0038	0.18	NO
105	FBXW11	FBXW11	FBXW11	14152	0.0033	0.18	NO
106	CSNK2B	CSNK2B	CSNK2B	14222	0.0022	0.18	NO
107	CTBP1	CTBP1	CTBP1	14396	0.000031	0.17	NO
108	PLCB2	PLCB2	PLCB2	14435	-0.00043	0.17	NO
109	MAPK9	MAPK9	MAPK9	14469	-0.00082	0.16	NO
110	DVL1	DVL1	DVL1	14489	-0.0012	0.16	NO
111	PPP2R1A	PPP2R1A	PPP2R1A	15096	-0.0092	0.14	NO
112	CTNNB1	CTNNB1	CTNNB1	15609	-0.017	0.12	NO
113	RAC1	RAC1	RAC1	15641	-0.018	0.12	NO
114	PRKCB	PRKCB	PRKCB	15728	-0.019	0.11	NO
115	PPP2R5A	PPP2R5A	PPP2R5A	15773	-0.02	0.11	NO
116	LRP6	LRP6	LRP6	16122	-0.025	0.097	NO
117	MAPK8	MAPK8	MAPK8	16187	-0.026	0.096	NO
118	PSEN1	PSEN1	PSEN1	16764	-0.036	0.072	NO
119	CXXC4	CXXC4	CXXC4	17112	-0.044	0.059	NO
120	RHOA	RHOA	RHOA	17320	-0.048	0.052	NO
121	ROCK2	ROCK2	ROCK2	17327	-0.049	0.054	NO
122	CCND3	CCND3	CCND3	17586	-0.055	0.045	NO
123	PLCB3	PLCB3	PLCB3	17598	-0.055	0.047	NO
124	LRP5	LRP5	LRP5	17703	-0.057	0.045	NO
125	NLK	NLK	NLK	17826	-0.06	0.042	NO
126	TCF7	TCF7	TCF7	18503	-0.08	0.016	NO
127	SOX17	SOX17	SOX17	18649	-0.086	0.013	NO
128	FZD4	FZD4	FZD4	18771	-0.09	0.012	NO
129	CTBP2	CTBP2	CTBP2	18782	-0.091	0.016	NO
130	PPP2R1B	PPP2R1B	PPP2R1B	18796	-0.091	0.019	NO
131	CCND2	CCND2	CCND2	18846	-0.093	0.021	NO
132	FRAT2	FRAT2	FRAT2	18907	-0.096	0.023	NO
133	MMP7	MMP7	MMP7	19115	-0.1	0.018	NO
134	FRAT1	FRAT1	FRAT1	19382	-0.11	0.012	NO
135	CER1	CER1	CER1	19707	-0.13	0.003	NO
136	WNT8B	WNT8B	WNT8B	19793	-0.13	0.0052	NO
137	TCF7L2	TCF7L2	TCF7L2	19868	-0.14	0.0081	NO
138	WNT1	WNT1	WNT1	19947	-0.14	0.011	NO
139	PRKCA	PRKCA	PRKCA	20209	-0.16	0.0066	NO
140	PLCB4	PLCB4	PLCB4	20795	-0.2	-0.01	NO
141	AXIN2	AXIN2	AXIN2	20883	-0.21	-0.0045	NO
142	DKK4	DKK4	DKK4	21319	-0.26	-0.012	NO
143	NFATC2	NFATC2	NFATC2	21793	-0.34	-0.018	NO
144	FZD5	FZD5	FZD5	21962	-0.38	-0.0079	NO
145	PRKACG	PRKACG	PRKACG	22333	-0.52	-0.0011	NO
146	PRKCG	PRKCG	PRKCG	22360	-0.53	0.022	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 OOCYTE MEIOSIS.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG OOCYTE MEIOSIS, 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 P53 SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GLI3	GLI3	GLI3	205	0.6	0.039	YES
2	WNT9A	WNT9A	WNT9A	213	0.6	0.087	YES
3	WNT7A	WNT7A	WNT7A	289	0.56	0.13	YES
4	FZD9	FZD9	FZD9	296	0.56	0.17	YES
5	SMO	SMO	SMO	345	0.55	0.22	YES
6	FZD10	FZD10	FZD10	349	0.54	0.26	YES
7	WNT7B	WNT7B	WNT7B	498	0.5	0.29	YES
8	WNT10B	WNT10B	WNT10B	626	0.47	0.32	YES
9	WNT6	WNT6	WNT6	723	0.45	0.36	YES
10	GLI2	GLI2	GLI2	922	0.42	0.38	YES
11	TCF7L1	TCF7L1	TCF7L1	1274	0.37	0.4	YES
12	WNT2B	WNT2B	WNT2B	1430	0.35	0.42	YES
13	WNT10A	WNT10A	WNT10A	1916	0.3	0.42	YES
14	FZD7	FZD7	FZD7	2024	0.3	0.44	YES
15	FZD6	FZD6	FZD6	2038	0.3	0.46	YES
16	WNT2	WNT2	WNT2	2116	0.29	0.48	YES
17	WNT3	WNT3	WNT3	2185	0.28	0.5	YES
18	GLI1	GLI1	GLI1	2407	0.26	0.51	YES
19	FZD1	FZD1	FZD1	2649	0.25	0.52	YES
20	FZD2	FZD2	FZD2	3153	0.22	0.52	YES
21	LEF1	LEF1	LEF1	3492	0.2	0.52	YES
22	DVL2	DVL2	DVL2	3580	0.2	0.53	YES
23	WNT5B	WNT5B	WNT5B	3955	0.18	0.53	YES
24	WNT5A	WNT5A	WNT5A	4096	0.18	0.54	YES
25	WNT4	WNT4	WNT4	4890	0.15	0.51	NO
26	DVL3	DVL3	DVL3	5016	0.14	0.52	NO
27	FZD8	FZD8	FZD8	5468	0.13	0.51	NO
28	APC2	APC2	APC2	5870	0.12	0.5	NO
29	WNT16	WNT16	WNT16	6044	0.12	0.5	NO
30	TP53	TP53	TP53	6654	0.1	0.48	NO
31	PTCH2	PTCH2	PTCH2	7223	0.091	0.47	NO
32	GSK3B	GSK3B	GSK3B	7774	0.082	0.45	NO
33	SUFU	SUFU	SUFU	9721	0.055	0.37	NO
34	FZD3	FZD3	FZD3	10803	0.042	0.32	NO
35	PTCH1	PTCH1	PTCH1	11024	0.04	0.32	NO
36	AXIN1	AXIN1	AXIN1	11300	0.037	0.31	NO
37	WNT11	WNT11	WNT11	11762	0.031	0.29	NO
38	HHIP	HHIP	HHIP	11849	0.03	0.29	NO
39	WNT9B	WNT9B	WNT9B	12808	0.019	0.25	NO
40	APC	APC	APC	13182	0.015	0.24	NO
41	DVL1	DVL1	DVL1	14489	-0.0012	0.18	NO
42	CTNNB1	CTNNB1	CTNNB1	15609	-0.017	0.13	NO
43	STK36	STK36	STK36	17347	-0.049	0.057	NO
44	TCF7	TCF7	TCF7	18503	-0.08	0.013	NO
45	FZD4	FZD4	FZD4	18771	-0.09	0.0086	NO
46	WNT8B	WNT8B	WNT8B	19793	-0.13	-0.026	NO
47	BMP2	BMP2	BMP2	19842	-0.14	-0.017	NO
48	TCF7L2	TCF7L2	TCF7L2	19868	-0.14	-0.0068	NO
49	WNT1	WNT1	WNT1	19947	-0.14	0.0011	NO
50	AXIN2	AXIN2	AXIN2	20883	-0.21	-0.023	NO
51	BMP4	BMP4	BMP4	21608	-0.3	-0.03	NO
52	FZD5	FZD5	FZD5	21962	-0.38	-0.015	NO
53	SHH	SHH	SHH	22562	-0.68	0.013	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 P53 SIGNALING PATHWAY.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG P53 SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG MTOR SIGNALING PATHWAY

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	COL11A1	COL11A1	COL11A1	62	0.74	0.046	YES
2	COL4A6	COL4A6	COL4A6	90	0.69	0.09	YES
3	ITGA2B	ITGA2B	ITGA2B	396	0.53	0.11	YES
4	COL6A6	COL6A6	COL6A6	450	0.52	0.14	YES
5	TNC	TNC	TNC	541	0.49	0.17	YES
6	LAMA1	LAMA1	LAMA1	573	0.48	0.2	YES
7	SPP1	SPP1	SPP1	676	0.46	0.23	YES
8	COL2A1	COL2A1	COL2A1	772	0.45	0.25	YES
9	SV2A	SV2A	SV2A	844	0.43	0.28	YES
10	THBS4	THBS4	THBS4	857	0.43	0.31	YES
11	RELN	RELN	RELN	1394	0.36	0.3	YES
12	GP1BB	GP1BB	GP1BB	1450	0.35	0.33	YES
13	ITGA11	ITGA11	ITGA11	2001	0.3	0.32	YES
14	TNN	TNN	TNN	2071	0.29	0.34	YES
15	FN1	FN1	FN1	2200	0.28	0.35	YES
16	SV2B	SV2B	SV2B	2261	0.28	0.37	YES
17	COL5A1	COL5A1	COL5A1	2403	0.26	0.38	YES
18	THBS2	THBS2	THBS2	2510	0.26	0.39	YES
19	COL5A3	COL5A3	COL5A3	2768	0.24	0.39	YES
20	COL6A2	COL6A2	COL6A2	2844	0.24	0.41	YES
21	COL1A1	COL1A1	COL1A1	2850	0.24	0.42	YES
22	COL1A2	COL1A2	COL1A2	2938	0.23	0.43	YES
23	COL6A1	COL6A1	COL6A1	3055	0.23	0.44	YES
24	COL3A1	COL3A1	COL3A1	3069	0.22	0.46	YES
25	COL5A2	COL5A2	COL5A2	3284	0.21	0.46	YES
26	IBSP	IBSP	IBSP	3686	0.19	0.46	YES
27	COL6A3	COL6A3	COL6A3	3928	0.18	0.46	YES
28	GP1BA	GP1BA	GP1BA	4136	0.18	0.46	YES
29	ITGA5	ITGA5	ITGA5	4277	0.17	0.46	YES
30	CD44	CD44	CD44	4283	0.17	0.48	YES
31	SDC2	SDC2	SDC2	4368	0.16	0.48	YES
32	LAMC2	LAMC2	LAMC2	4441	0.16	0.49	YES
33	COMP	COMP	COMP	4485	0.16	0.5	YES
34	THBS1	THBS1	THBS1	4546	0.16	0.51	YES
35	LAMB4	LAMB4	LAMB4	4751	0.15	0.51	YES
36	CD36	CD36	CD36	4936	0.15	0.51	YES
37	SDC1	SDC1	SDC1	5213	0.14	0.51	YES
38	ITGB8	ITGB8	ITGB8	5305	0.13	0.51	YES
39	SV2C	SV2C	SV2C	5316	0.13	0.52	YES
40	ITGAV	ITGAV	ITGAV	5879	0.12	0.5	NO
41	LAMA2	LAMA2	LAMA2	6105	0.11	0.5	NO
42	LAMB3	LAMB3	LAMB3	6119	0.11	0.51	NO
43	THBS3	THBS3	THBS3	6633	0.1	0.49	NO
44	HMMR	HMMR	HMMR	6714	0.1	0.49	NO
45	ITGA4	ITGA4	ITGA4	6945	0.096	0.49	NO
46	ITGA6	ITGA6	ITGA6	6968	0.096	0.5	NO
47	LAMC1	LAMC1	LAMC1	7059	0.094	0.5	NO
48	LAMA5	LAMA5	LAMA5	7235	0.091	0.5	NO
49	AGRN	AGRN	AGRN	7285	0.09	0.5	NO
50	ITGB6	ITGB6	ITGB6	7391	0.088	0.5	NO
51	COL4A2	COL4A2	COL4A2	7502	0.087	0.5	NO
52	ITGB5	ITGB5	ITGB5	7576	0.086	0.5	NO
53	ITGA2	ITGA2	ITGA2	7766	0.082	0.5	NO
54	COL11A2	COL11A2	COL11A2	8088	0.077	0.49	NO
55	LAMA3	LAMA3	LAMA3	8239	0.075	0.49	NO
56	LAMB1	LAMB1	LAMB1	8600	0.07	0.48	NO
57	LAMA4	LAMA4	LAMA4	8633	0.069	0.48	NO
58	ITGA9	ITGA9	ITGA9	8813	0.067	0.48	NO
59	ITGB4	ITGB4	ITGB4	8828	0.066	0.48	NO
60	SDC3	SDC3	SDC3	9175	0.062	0.47	NO
61	COL4A1	COL4A1	COL4A1	10380	0.047	0.42	NO
62	ITGB1	ITGB1	ITGB1	10591	0.045	0.42	NO
63	ITGA3	ITGA3	ITGA3	10715	0.043	0.41	NO
64	LAMB2	LAMB2	LAMB2	12980	0.017	0.31	NO
65	CD47	CD47	CD47	13090	0.016	0.31	NO
66	ITGA1	ITGA1	ITGA1	13315	0.013	0.3	NO
67	ITGB3	ITGB3	ITGB3	14455	-0.0006	0.25	NO
68	HSPG2	HSPG2	HSPG2	14485	-0.0011	0.25	NO
69	ITGB7	ITGB7	ITGB7	16105	-0.025	0.18	NO
70	LAMC3	LAMC3	LAMC3	16752	-0.036	0.16	NO
71	GP5	GP5	GP5	16961	-0.041	0.15	NO
72	ITGA7	ITGA7	ITGA7	17913	-0.063	0.11	NO
73	TNR	TNR	TNR	18240	-0.073	0.1	NO
74	SDC4	SDC4	SDC4	18273	-0.074	0.1	NO
75	ITGA10	ITGA10	ITGA10	18676	-0.087	0.093	NO
76	TNXB	TNXB	TNXB	18978	-0.098	0.086	NO
77	DAG1	DAG1	DAG1	18996	-0.099	0.092	NO
78	COL4A4	COL4A4	COL4A4	19248	-0.11	0.088	NO
79	VWF	VWF	VWF	19583	-0.12	0.081	NO
80	ITGA8	ITGA8	ITGA8	20248	-0.16	0.063	NO
81	CHAD	CHAD	CHAD	20537	-0.18	0.062	NO
82	GP6	GP6	GP6	21320	-0.26	0.044	NO
83	GP9	GP9	GP9	21802	-0.34	0.046	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 MTOR SIGNALING PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG MTOR SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype 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 G1 PATHWAY	27	genes.ES.table	0.29	0.9	0.58	1	1	0.15	0.085	0.14	1	0.75
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.34	1.2	0.25	1	0.97	1	0.66	0.34	1	0.67
BIOCARTA MAPK PATHWAY	85	genes.ES.table	0.24	1.1	0.42	1	0.99	0.4	0.23	0.31	1	0.71
BIOCARTA IL1R PATHWAY	32	genes.ES.table	0.42	1.3	0.2	1	0.95	0.19	0.084	0.17	1	0.82
KEGG OXIDATIVE PHOSPHORYLATION	112	genes.ES.table	0.24	1.1	0.37	1	0.99	0.027	0.023	0.026	1	0.68
KEGG ETHER LIPID METABOLISM	30	genes.ES.table	0.3	0.93	0.56	1	1	0.17	0.057	0.16	1	0.72
KEGG ARACHIDONIC ACID METABOLISM	52	genes.ES.table	0.44	1.2	0.23	1	0.97	0.33	0.098	0.3	1	0.62
KEGG RETINOL METABOLISM	52	genes.ES.table	0.36	0.87	0.62	1	1	0.23	0.088	0.21	1	0.72
KEGG RIBOSOME	81	genes.ES.table	0.44	1.2	0.3	1	0.96	0.56	0.26	0.41	1	0.76
KEGG RNA POLYMERASE	28	genes.ES.table	0.34	1.1	0.3	1	0.97	0.96	0.57	0.42	1	0.62

genes ES table in pathway: BIOCARTA G1 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	ATP6V0A4	ATP6V0A4	ATP6V0A4	248	0.6	0.078	YES
2	CXCR2	CXCR2	CXCR2	275	0.58	0.16	YES
3	PTPRZ1	PTPRZ1	PTPRZ1	344	0.53	0.24	YES
4	MAPK10	MAPK10	MAPK10	1141	0.25	0.24	YES
5	HBEGF	HBEGF	HBEGF	1202	0.24	0.27	YES
6	CXCR1	CXCR1	CXCR1	2670	0.1	0.22	YES
7	MAP2K4	MAP2K4	MAP2K4	2784	0.1	0.23	YES
8	ATP6V1B1	ATP6V1B1	ATP6V1B1	2792	0.099	0.25	YES
9	MAPK13	MAPK13	MAPK13	2920	0.093	0.26	YES
10	ATP6V1D	ATP6V1D	ATP6V1D	2929	0.092	0.27	YES
11	EGFR	EGFR	EGFR	2975	0.09	0.28	YES
12	NFKBIA	NFKBIA	NFKBIA	3032	0.087	0.29	YES
13	MAPK11	MAPK11	MAPK11	3097	0.084	0.3	YES
14	ATP6V0C	ATP6V0C	ATP6V0C	3270	0.077	0.3	YES
15	ADAM17	ADAM17	ADAM17	3301	0.075	0.32	YES
16	ATP6V1F	ATP6V1F	ATP6V1F	3315	0.075	0.32	YES
17	TJP1	TJP1	TJP1	3742	0.061	0.32	NO
18	ATP6V0D1	ATP6V0D1	ATP6V0D1	3831	0.058	0.32	NO
19	CSK	CSK	CSK	3990	0.053	0.32	NO
20	ATP6V1E1	ATP6V1E1	ATP6V1E1	4310	0.044	0.31	NO
21	RAC1	RAC1	RAC1	4433	0.041	0.31	NO
22	PLCG2	PLCG2	PLCG2	4644	0.036	0.31	NO
23	F11R	F11R	F11R	4647	0.036	0.32	NO
24	IKBKG	IKBKG	IKBKG	4667	0.035	0.32	NO
25	JUN	JUN	JUN	4811	0.032	0.32	NO
26	ATP6V1H	ATP6V1H	ATP6V1H	4942	0.029	0.32	NO
27	ATP6V1B2	ATP6V1B2	ATP6V1B2	4969	0.029	0.32	NO
28	ATP6V1A	ATP6V1A	ATP6V1A	5180	0.024	0.31	NO
29	ATP6V0A1	ATP6V0A1	ATP6V0A1	5716	0.015	0.29	NO
30	ATP6V1G1	ATP6V1G1	ATP6V1G1	5942	0.011	0.28	NO
31	RELA	RELA	RELA	6223	0.0068	0.27	NO
32	MAPK14	MAPK14	MAPK14	6386	0.0045	0.27	NO
33	CDC42	CDC42	CDC42	7386	-0.0092	0.22	NO
34	NFKB1	NFKB1	NFKB1	7626	-0.012	0.22	NO
35	IKBKB	IKBKB	IKBKB	7634	-0.012	0.22	NO
36	ATP6V1E2	ATP6V1E2	ATP6V1E2	7737	-0.014	0.22	NO
37	MAPK12	MAPK12	MAPK12	8016	-0.017	0.2	NO
38	ATP6V0B	ATP6V0B	ATP6V0B	8172	-0.019	0.2	NO
39	PAK1	PAK1	PAK1	8314	-0.02	0.2	NO
40	GIT1	GIT1	GIT1	9133	-0.03	0.17	NO
41	ATP6AP1	ATP6AP1	ATP6AP1	9443	-0.034	0.16	NO
42	CCL5	CCL5	CCL5	10397	-0.044	0.12	NO
43	NOD1	NOD1	NOD1	10650	-0.047	0.12	NO
44	IL8	IL8	IL8	11033	-0.052	0.11	NO
45	ADAM10	ADAM10	ADAM10	11104	-0.052	0.11	NO
46	PLCG1	PLCG1	PLCG1	11286	-0.054	0.11	NO
47	PTPN11	PTPN11	PTPN11	11309	-0.054	0.12	NO
48	CHUK	CHUK	CHUK	11510	-0.057	0.12	NO
49	ATP6V1C2	ATP6V1C2	ATP6V1C2	12007	-0.063	0.11	NO
50	CXCL1	CXCL1	CXCL1	12366	-0.068	0.1	NO
51	SRC	SRC	SRC	12645	-0.072	0.1	NO
52	CASP3	CASP3	CASP3	12729	-0.073	0.11	NO
53	ATP6V1C1	ATP6V1C1	ATP6V1C1	12797	-0.074	0.12	NO
54	TCIRG1	TCIRG1	TCIRG1	12926	-0.076	0.12	NO
55	MAPK8	MAPK8	MAPK8	13389	-0.083	0.11	NO
56	MAPK9	MAPK9	MAPK9	13916	-0.091	0.1	NO
57	ATP6V0A2	ATP6V0A2	ATP6V0A2	14904	-0.11	0.076	NO
58	LYN	LYN	LYN	16912	-0.15	0.011	NO
59	MET	MET	MET	16997	-0.16	0.03	NO
60	MAP3K14	MAP3K14	MAP3K14	17251	-0.16	0.043	NO
61	ATP6V0D2	ATP6V0D2	ATP6V0D2	17374	-0.16	0.062	NO
62	ATP6V0E2	ATP6V0E2	ATP6V0E2	18399	-0.2	0.046	NO
63	JAM2	JAM2	JAM2	19614	-0.24	0.027	NO
64	IGSF5	IGSF5	IGSF5	19950	-0.25	0.05	NO
65	ATP6V1G2	ATP6V1G2	ATP6V1G2	20136	-0.26	0.08	NO
66	JAM3	JAM3	JAM3	20246	-0.26	0.11	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 G1 PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 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	IL1A	IL1A	IL1A	258	0.6	0.13	YES
2	IL1RN	IL1RN	IL1RN	259	0.6	0.28	YES
3	IFNA1	IFNA1	IFNA1	646	0.37	0.35	YES
4	IL1RAP	IL1RAP	IL1RAP	1469	0.21	0.36	YES
5	TGFB1	TGFB1	TGFB1	1630	0.19	0.4	YES
6	TOLLIP	TOLLIP	TOLLIP	1929	0.16	0.42	YES
7	NFKBIA	NFKBIA	NFKBIA	3032	0.087	0.4	NO
8	IL1B	IL1B	IL1B	3535	0.067	0.39	NO
9	TAB1	TAB1	TAB1	3574	0.066	0.4	NO
10	MYD88	MYD88	MYD88	3909	0.055	0.4	NO
11	TNF	TNF	TNF	4526	0.038	0.38	NO
12	JUN	JUN	JUN	4811	0.032	0.38	NO
13	MAP3K1	MAP3K1	MAP3K1	5089	0.026	0.37	NO
14	RELA	RELA	RELA	6223	0.0068	0.32	NO
15	MAPK14	MAPK14	MAPK14	6386	0.0045	0.32	NO
16	ECSIT	ECSIT	ECSIT	7497	-0.011	0.27	NO
17	NFKB1	NFKB1	NFKB1	7626	-0.012	0.27	NO
18	IKBKB	IKBKB	IKBKB	7634	-0.012	0.27	NO
19	TRAF6	TRAF6	TRAF6	7791	-0.014	0.27	NO
20	MAP3K7	MAP3K7	MAP3K7	8295	-0.02	0.25	NO
21	IRAK1	IRAK1	IRAK1	8975	-0.028	0.23	NO
22	MAP2K3	MAP2K3	MAP2K3	9112	-0.03	0.23	NO
23	TGFB3	TGFB3	TGFB3	9283	-0.032	0.23	NO
24	CHUK	CHUK	CHUK	11510	-0.057	0.15	NO
25	IRAK2	IRAK2	IRAK2	12933	-0.076	0.1	NO
26	MAPK8	MAPK8	MAPK8	13389	-0.083	0.1	NO
27	IFNB1	IFNB1	IFNB1	16747	-0.15	-0.0087	NO
28	MAP3K14	MAP3K14	MAP3K14	17251	-0.16	0.0079	NO
29	TGFB2	TGFB2	TGFB2	17999	-0.18	0.019	NO
30	IL6	IL6	IL6	18099	-0.19	0.06	NO
31	MAP2K6	MAP2K6	MAP2K6	20866	-0.3	0.0094	NO
32	IRAK3	IRAK3	IRAK3	21263	-0.32	0.07	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 MAPK 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	TP53AIP1	TP53AIP1	TP53AIP1	222	0.64	0.075	YES
2	SFN	SFN	SFN	538	0.41	0.12	YES
3	SERPINB5	SERPINB5	SERPINB5	676	0.36	0.16	YES
4	SESN3	SESN3	SESN3	707	0.35	0.2	YES
5	PERP	PERP	PERP	908	0.3	0.24	YES
6	BAI1	BAI1	BAI1	1217	0.24	0.25	YES
7	TP73	TP73	TP73	1368	0.22	0.28	YES
8	RPRM	RPRM	RPRM	1612	0.19	0.29	YES
9	CDKN1A	CDKN1A	CDKN1A	1942	0.16	0.3	YES
10	TP53I3	TP53I3	TP53I3	2066	0.15	0.31	YES
11	PMAIP1	PMAIP1	PMAIP1	2720	0.1	0.3	NO
12	DDB2	DDB2	DDB2	2760	0.1	0.31	NO
13	CD82	CD82	CD82	3189	0.08	0.3	NO
14	SESN2	SESN2	SESN2	3329	0.074	0.31	NO
15	CCNG2	CCNG2	CCNG2	3847	0.057	0.29	NO
16	CCND1	CCND1	CCND1	3894	0.056	0.3	NO
17	CCNE1	CCNE1	CCNE1	4952	0.029	0.25	NO
18	MDM2	MDM2	MDM2	5188	0.024	0.25	NO
19	SHISA5	SHISA5	SHISA5	5379	0.021	0.24	NO
20	SERPINE1	SERPINE1	SERPINE1	5545	0.018	0.24	NO
21	GADD45A	GADD45A	GADD45A	5969	0.011	0.22	NO
22	TSC2	TSC2	TSC2	6489	0.0028	0.2	NO
23	SIAH1	SIAH1	SIAH1	6682	-0.00025	0.19	NO
24	EI24	EI24	EI24	6933	-0.0035	0.18	NO
25	PTEN	PTEN	PTEN	6985	-0.0041	0.18	NO
26	CCND2	CCND2	CCND2	7534	-0.011	0.15	NO
27	CDK6	CDK6	CDK6	7823	-0.015	0.14	NO
28	RFWD2	RFWD2	RFWD2	8042	-0.017	0.14	NO
29	CYCS	CYCS	CYCS	8063	-0.018	0.14	NO
30	ZMAT3	ZMAT3	ZMAT3	8789	-0.026	0.11	NO
31	FAS	FAS	FAS	8868	-0.027	0.11	NO
32	CCNB1	CCNB1	CCNB1	8935	-0.028	0.11	NO
33	CASP9	CASP9	CASP9	9178	-0.03	0.1	NO
34	RRM2	RRM2	RRM2	9522	-0.034	0.092	NO
35	BAX	BAX	BAX	9769	-0.037	0.087	NO
36	RRM2B	RRM2B	RRM2B	10485	-0.046	0.061	NO
37	CCNB2	CCNB2	CCNB2	10599	-0.047	0.063	NO
38	CDK4	CDK4	CDK4	10895	-0.05	0.056	NO
39	GADD45B	GADD45B	GADD45B	11166	-0.053	0.052	NO
40	PPM1D	PPM1D	PPM1D	11203	-0.053	0.057	NO
41	CHEK2	CHEK2	CHEK2	11636	-0.058	0.046	NO
42	ATR	ATR	ATR	12249	-0.066	0.028	NO
43	MDM4	MDM4	MDM4	12631	-0.072	0.021	NO
44	CASP3	CASP3	CASP3	12729	-0.073	0.026	NO
45	CCNG1	CCNG1	CCNG1	13025	-0.078	0.024	NO
46	SESN1	SESN1	SESN1	13038	-0.078	0.034	NO
47	CCND3	CCND3	CCND3	13339	-0.082	0.032	NO
48	CDK2	CDK2	CDK2	14035	-0.093	0.014	NO
49	CHEK1	CHEK1	CHEK1	14175	-0.096	0.02	NO
50	BID	BID	BID	14218	-0.096	0.031	NO
51	CDK1	CDK1	CDK1	14307	-0.098	0.041	NO
52	TP53	TP53	TP53	14399	-0.1	0.05	NO
53	CCNE2	CCNE2	CCNE2	14411	-0.1	0.063	NO
54	RCHY1	RCHY1	RCHY1	14483	-0.1	0.073	NO
55	TNFRSF10B	TNFRSF10B	TNFRSF10B	14962	-0.11	0.067	NO
56	CASP8	CASP8	CASP8	15310	-0.12	0.067	NO
57	IGFBP3	IGFBP3	IGFBP3	15915	-0.13	0.058	NO
58	GTSE1	GTSE1	GTSE1	16457	-0.14	0.053	NO
59	IGF1	IGF1	IGF1	16698	-0.15	0.062	NO
60	THBS1	THBS1	THBS1	17281	-0.16	0.058	NO
61	ATM	ATM	ATM	17667	-0.17	0.065	NO
62	APAF1	APAF1	APAF1	18488	-0.2	0.055	NO
63	CDKN2A	CDKN2A	CDKN2A	18709	-0.2	0.073	NO
64	BBC3	BBC3	BBC3	19042	-0.22	0.088	NO
65	GADD45G	GADD45G	GADD45G	20558	-0.28	0.059	NO
66	CCNB3	CCNB3	CCNB3	21115	-0.31	0.076	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 MAPK PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MAPK 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	RPL3L	RPL3L	RPL3L	441	0.46	0.15	YES
2	RPSA	RPSA	RPSA	1507	0.2	0.18	YES
3	RPL7	RPL7	RPL7	2553	0.11	0.17	YES
4	RPS28	RPS28	RPS28	3046	0.086	0.18	YES
5	RPL22L1	RPL22L1	RPL22L1	3144	0.082	0.21	YES
6	RPS27	RPS27	RPS27	3257	0.077	0.23	YES
7	RPL18A	RPL18A	RPL18A	4039	0.052	0.21	YES
8	RPS2	RPS2	RPS2	4334	0.043	0.22	YES
9	RPS15	RPS15	RPS15	4446	0.04	0.23	YES
10	RPLP1	RPLP1	RPLP1	4516	0.039	0.24	YES
11	RPL13A	RPL13A	RPL13A	4721	0.034	0.24	YES
12	RPS7	RPS7	RPS7	4736	0.034	0.25	YES
13	RPLP0	RPLP0	RPLP0	4832	0.032	0.26	YES
14	RPL36	RPL36	RPL36	4855	0.031	0.27	YES
15	RPL29	RPL29	RPL29	4887	0.03	0.28	YES
16	RPL37	RPL37	RPL37	4951	0.029	0.29	YES
17	RPL24	RPL24	RPL24	5025	0.027	0.3	YES
18	RPL4	RPL4	RPL4	5072	0.026	0.3	YES
19	RPL28	RPL28	RPL28	5123	0.025	0.31	YES
20	RPL38	RPL38	RPL38	5187	0.024	0.32	YES
21	RPL35	RPL35	RPL35	5242	0.023	0.32	YES
22	RPL10	RPL10	RPL10	5274	0.022	0.33	YES
23	RPL13	RPL13	RPL13	5288	0.022	0.34	YES
24	RPS12	RPS12	RPS12	5336	0.021	0.34	YES
25	RPL35A	RPL35A	RPL35A	5338	0.021	0.35	YES
26	RPS9	RPS9	RPS9	5414	0.02	0.35	YES
27	RPL39	RPL39	RPL39	5431	0.02	0.36	YES
28	RPL27A	RPL27A	RPL27A	5460	0.019	0.37	YES
29	UBA52	UBA52	UBA52	5488	0.019	0.37	YES
30	RPS23	RPS23	RPS23	5526	0.018	0.38	YES
31	RPL27	RPL27	RPL27	5530	0.018	0.38	YES
32	RPS15A	RPS15A	RPS15A	5531	0.018	0.39	YES
33	RPL10A	RPL10A	RPL10A	5593	0.017	0.39	YES
34	RPS3A	RPS3A	RPS3A	5596	0.017	0.4	YES
35	RPL6	RPL6	RPL6	5674	0.016	0.4	YES
36	RPL26	RPL26	RPL26	5701	0.015	0.41	YES
37	RPS29	RPS29	RPS29	5711	0.015	0.41	YES
38	RPL36AL	RPL36AL	RPL36AL	5748	0.014	0.42	YES
39	RPS18	RPS18	RPS18	5758	0.014	0.42	YES
40	RPL32	RPL32	RPL32	5799	0.014	0.42	YES
41	RPL8	RPL8	RPL8	5805	0.014	0.43	YES
42	RPL26L1	RPL26L1	RPL26L1	5838	0.013	0.43	YES
43	RPS16	RPS16	RPS16	5902	0.012	0.43	YES
44	RPL3	RPL3	RPL3	5921	0.012	0.44	YES
45	RPS27A	RPS27A	RPS27A	5985	0.011	0.44	YES
46	RPS25	RPS25	RPS25	6175	0.0074	0.43	NO
47	RPS20	RPS20	RPS20	6206	0.007	0.43	NO
48	RPS24	RPS24	RPS24	6254	0.0063	0.43	NO
49	RPS13	RPS13	RPS13	6307	0.0056	0.43	NO
50	RPL14	RPL14	RPL14	6321	0.0054	0.43	NO
51	RPL11	RPL11	RPL11	6339	0.0051	0.44	NO
52	RPLP2	RPLP2	RPLP2	6432	0.0037	0.43	NO
53	FAU	FAU	FAU	6459	0.0032	0.43	NO
54	RPL12	RPL12	RPL12	6492	0.0027	0.43	NO
55	RPL7A	RPL7A	RPL7A	6569	0.0014	0.43	NO
56	RPS8	RPS8	RPS8	6627	0.00059	0.43	NO
57	RPS4X	RPS4X	RPS4X	6756	-0.0013	0.42	NO
58	RPL34	RPL34	RPL34	6771	-0.0015	0.42	NO
59	RPS3	RPS3	RPS3	7033	-0.0047	0.41	NO
60	RPS19	RPS19	RPS19	7160	-0.0063	0.41	NO
61	RPL9	RPL9	RPL9	7358	-0.0089	0.4	NO
62	MRPL13	MRPL13	MRPL13	7432	-0.0099	0.4	NO
63	RPS11	RPS11	RPS11	7578	-0.012	0.4	NO
64	RSL24D1	RSL24D1	RSL24D1	7586	-0.012	0.41	NO
65	RPS5	RPS5	RPS5	7647	-0.012	0.41	NO
66	RPL19	RPL19	RPL19	7759	-0.014	0.41	NO
67	RPL41	RPL41	RPL41	7763	-0.014	0.41	NO
68	RPL31	RPL31	RPL31	7821	-0.015	0.42	NO
69	RPS6	RPS6	RPS6	7995	-0.017	0.41	NO
70	RPL23	RPL23	RPL23	8033	-0.017	0.42	NO
71	RPL15	RPL15	RPL15	8095	-0.018	0.42	NO
72	RPL37A	RPL37A	RPL37A	8226	-0.02	0.42	NO
73	RPL5	RPL5	RPL5	8454	-0.022	0.42	NO
74	RPS21	RPS21	RPS21	8572	-0.024	0.42	NO
75	RPL22	RPL22	RPL22	8657	-0.025	0.43	NO
76	RPL30	RPL30	RPL30	9094	-0.029	0.42	NO
77	RPL23A	RPL23A	RPL23A	9186	-0.03	0.43	NO
78	RPS26	RPS26	RPS26	12278	-0.067	0.32	NO
79	RPL21	RPL21	RPL21	12872	-0.075	0.32	NO
80	RPS27L	RPS27L	RPS27L	16349	-0.14	0.22	NO
81	RPL10L	RPL10L	RPL10L	18128	-0.19	0.21	NO

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

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	1373	0.22	-0.0082	YES
2	THOC3	THOC3	THOC3	3506	0.068	-0.086	YES
3	PLRG1	PLRG1	PLRG1	4556	0.038	-0.12	YES
4	HSPA6	HSPA6	HSPA6	4566	0.037	-0.12	YES
5	ZMAT2	ZMAT2	ZMAT2	4829	0.032	-0.12	YES
6	AQR	AQR	AQR	5417	0.02	-0.14	YES
7	PCBP1	PCBP1	PCBP1	5443	0.019	-0.14	YES
8	SF3B5	SF3B5	SF3B5	5577	0.017	-0.14	YES
9	CCDC12	CCDC12	CCDC12	5601	0.017	-0.14	YES
10	PRPF40B	PRPF40B	PRPF40B	5671	0.016	-0.14	YES
11	SF3B14	SF3B14	SF3B14	5960	0.011	-0.14	YES
12	EIF4A3	EIF4A3	EIF4A3	6069	0.0093	-0.15	YES
13	SNRPD3	SNRPD3	SNRPD3	6168	0.0075	-0.15	YES
14	SNRPD2	SNRPD2	SNRPD2	6256	0.0062	-0.15	YES
15	NHP2L1	NHP2L1	NHP2L1	6328	0.0053	-0.15	YES
16	SF3B4	SF3B4	SF3B4	6396	0.0043	-0.16	YES
17	HSPA1B	HSPA1B	HSPA1B	6538	0.0019	-0.16	YES
18	PUF60	PUF60	PUF60	6718	-0.00074	-0.17	YES
19	SNRPA1	SNRPA1	SNRPA1	6791	-0.0018	-0.17	YES
20	SF3A2	SF3A2	SF3A2	6799	-0.0019	-0.17	YES
21	TXNL4A	TXNL4A	TXNL4A	6972	-0.004	-0.18	YES
22	SNRPF	SNRPF	SNRPF	7097	-0.0055	-0.18	YES
23	DHX38	DHX38	DHX38	7189	-0.0067	-0.18	YES
24	U2AF2	U2AF2	U2AF2	7295	-0.0081	-0.19	YES
25	SF3B3	SF3B3	SF3B3	7303	-0.0082	-0.19	YES
26	USP39	USP39	USP39	7368	-0.009	-0.19	YES
27	RBM8A	RBM8A	RBM8A	7471	-0.01	-0.19	YES
28	LSM3	LSM3	LSM3	7761	-0.014	-0.2	YES
29	CWC15	CWC15	CWC15	7779	-0.014	-0.2	YES
30	PPIL1	PPIL1	PPIL1	7810	-0.015	-0.19	YES
31	PRPF31	PRPF31	PRPF31	7881	-0.016	-0.19	YES
32	SNW1	SNW1	SNW1	7959	-0.016	-0.19	YES
33	HSPA1A	HSPA1A	HSPA1A	8010	-0.017	-0.19	YES
34	SMNDC1	SMNDC1	SMNDC1	8093	-0.018	-0.19	YES
35	HSPA1L	HSPA1L	HSPA1L	8139	-0.018	-0.19	YES
36	HNRNPC	HNRNPC	HNRNPC	8166	-0.019	-0.18	YES
37	SART1	SART1	SART1	8175	-0.019	-0.18	YES
38	XAB2	XAB2	XAB2	8219	-0.019	-0.18	YES
39	BCAS2	BCAS2	BCAS2	8220	-0.019	-0.17	YES
40	HSPA8	HSPA8	HSPA8	8307	-0.02	-0.17	YES
41	PRPF18	PRPF18	PRPF18	8321	-0.021	-0.17	YES
42	PPIE	PPIE	PPIE	8334	-0.021	-0.16	YES
43	PRPF19	PRPF19	PRPF19	8439	-0.022	-0.16	YES
44	PHF5A	PHF5A	PHF5A	8468	-0.022	-0.16	YES
45	DHX8	DHX8	DHX8	8515	-0.023	-0.16	YES
46	EFTUD2	EFTUD2	EFTUD2	8525	-0.023	-0.15	YES
47	SNRNP70	SNRNP70	SNRNP70	8570	-0.024	-0.15	YES
48	LSM7	LSM7	LSM7	8648	-0.024	-0.14	YES
49	PRPF8	PRPF8	PRPF8	8880	-0.027	-0.15	YES
50	WBP11	WBP11	WBP11	8905	-0.027	-0.14	YES
51	TRA2B	TRA2B	TRA2B	8921	-0.027	-0.14	YES
52	SNRPB	SNRPB	SNRPB	8960	-0.028	-0.13	YES
53	SNRPA	SNRPA	SNRPA	8982	-0.028	-0.13	YES
54	DDX5	DDX5	DDX5	8987	-0.028	-0.12	YES
55	SNRNP40	SNRNP40	SNRNP40	9003	-0.028	-0.12	YES
56	SF3A1	SF3A1	SF3A1	9020	-0.029	-0.11	YES
57	SF3B2	SF3B2	SF3B2	9076	-0.029	-0.1	YES
58	HNRNPM	HNRNPM	HNRNPM	9106	-0.03	-0.098	YES
59	SF3A3	SF3A3	SF3A3	9308	-0.032	-0.1	YES
60	SNRPE	SNRPE	SNRPE	9313	-0.032	-0.092	YES
61	BUD31	BUD31	BUD31	9328	-0.032	-0.086	YES
62	DDX42	DDX42	DDX42	9434	-0.034	-0.082	YES
63	TCERG1	TCERG1	TCERG1	9442	-0.034	-0.075	YES
64	HNRNPA1	HNRNPA1	HNRNPA1	9540	-0.035	-0.071	YES
65	RBM25	RBM25	RBM25	9833	-0.038	-0.075	YES
66	ACIN1	ACIN1	ACIN1	9891	-0.039	-0.068	YES
67	THOC1	THOC1	THOC1	9893	-0.039	-0.059	YES
68	PRPF40A	PRPF40A	PRPF40A	9909	-0.039	-0.051	YES
69	LSM2	LSM2	LSM2	9937	-0.039	-0.043	YES
70	RBM22	RBM22	RBM22	9981	-0.04	-0.035	YES
71	HNRNPK	HNRNPK	HNRNPK	9998	-0.04	-0.027	YES
72	MAGOHB	MAGOHB	MAGOHB	10053	-0.04	-0.02	YES
73	SNRPG	SNRPG	SNRPG	10079	-0.04	-0.011	YES
74	PQBP1	PQBP1	PQBP1	10214	-0.042	-0.0073	YES
75	PRPF4	PRPF4	PRPF4	10248	-0.043	0.0013	YES
76	LSM5	LSM5	LSM5	10383	-0.044	0.0058	YES
77	RBM17	RBM17	RBM17	10438	-0.045	0.014	YES
78	DHX15	DHX15	DHX15	10469	-0.045	0.023	YES
79	CTNNBL1	CTNNBL1	CTNNBL1	10537	-0.046	0.031	YES
80	CHERP	CHERP	CHERP	10615	-0.047	0.039	YES
81	MAGOH	MAGOH	MAGOH	10616	-0.047	0.05	YES
82	SLU7	SLU7	SLU7	10619	-0.047	0.061	YES
83	DDX46	DDX46	DDX46	10622	-0.047	0.072	YES
84	PPIH	PPIH	PPIH	10854	-0.05	0.073	YES
85	SNRPD1	SNRPD1	SNRPD1	10929	-0.05	0.082	YES
86	PRPF6	PRPF6	PRPF6	10980	-0.051	0.091	YES
87	DHX16	DHX16	DHX16	11048	-0.052	0.1	YES
88	LSM4	LSM4	LSM4	11122	-0.052	0.11	YES
89	U2AF1	U2AF1	U2AF1	11159	-0.053	0.12	YES
90	DDX23	DDX23	DDX23	11237	-0.054	0.13	YES
91	SNRPC	SNRPC	SNRPC	11253	-0.054	0.14	YES
92	LSM6	LSM6	LSM6	11283	-0.054	0.15	YES
93	TRA2A	TRA2A	TRA2A	11499	-0.057	0.16	YES
94	HNRNPU	HNRNPU	HNRNPU	11587	-0.058	0.17	YES
95	SF3B1	SF3B1	SF3B1	11607	-0.058	0.18	YES
96	HNRNPA3	HNRNPA3	HNRNPA3	11662	-0.059	0.19	YES
97	PRPF38A	PRPF38A	PRPF38A	11864	-0.061	0.2	YES
98	CDC40	CDC40	CDC40	11990	-0.063	0.21	YES
99	SYF2	SYF2	SYF2	12045	-0.064	0.22	YES
100	SNRNP200	SNRNP200	SNRNP200	12075	-0.064	0.23	YES
101	SNRNP27	SNRNP27	SNRNP27	12646	-0.072	0.22	YES
102	RBMX	RBMX	RBMX	12957	-0.076	0.23	YES
103	PRPF3	PRPF3	PRPF3	13659	-0.087	0.22	YES
104	NCBP1	NCBP1	NCBP1	13859	-0.09	0.23	YES
105	CRNKL1	CRNKL1	CRNKL1	13957	-0.092	0.25	YES
106	CDC5L	CDC5L	CDC5L	14087	-0.094	0.26	YES
107	NAA38	NAA38	NAA38	14250	-0.097	0.28	YES
108	PRPF38B	PRPF38B	PRPF38B	14336	-0.098	0.3	YES
109	SNRPB2	SNRPB2	SNRPB2	14497	-0.1	0.32	YES
110	THOC2	THOC2	THOC2	14572	-0.1	0.34	YES
111	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	15285	-0.12	0.33	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 OXIDATIVE PHOSPHORYLATION.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG OXIDATIVE PHOSPHORYLATION, 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 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	CDKN1A	CDKN1A	CDKN1A	1942	0.16	0.05	YES
2	HRAS	HRAS	HRAS	1986	0.15	0.18	YES
3	NFKBIA	NFKBIA	NFKBIA	3032	0.087	0.21	YES
4	CCND1	CCND1	CCND1	3894	0.056	0.22	YES
5	RAC1	RAC1	RAC1	4433	0.041	0.23	YES
6	IKBKG	IKBKG	IKBKG	4667	0.035	0.25	YES
7	CCNE1	CCNE1	CCNE1	4952	0.029	0.26	YES
8	RB1	RB1	RB1	5102	0.026	0.28	YES
9	MAPK3	MAPK3	MAPK3	5113	0.026	0.3	YES
10	RAF1	RAF1	RAF1	5303	0.022	0.31	YES
11	TFDP1	TFDP1	TFDP1	5694	0.015	0.3	YES
12	PIK3CA	PIK3CA	PIK3CA	5793	0.014	0.31	YES
13	RELA	RELA	RELA	6223	0.0068	0.3	YES
14	MAPK1	MAPK1	MAPK1	6427	0.0038	0.29	YES
15	NFKB1	NFKB1	NFKB1	7626	-0.012	0.25	YES
16	IKBKB	IKBKB	IKBKB	7634	-0.012	0.26	YES
17	CDK6	CDK6	CDK6	7823	-0.015	0.27	YES
18	RHOA	RHOA	RHOA	8068	-0.018	0.27	YES
19	PAK1	PAK1	PAK1	8314	-0.02	0.28	YES
20	AKT1	AKT1	AKT1	9715	-0.036	0.25	YES
21	CDK4	CDK4	CDK4	10895	-0.05	0.24	YES
22	CHUK	CHUK	CHUK	11510	-0.057	0.26	YES
23	CDKN1B	CDKN1B	CDKN1B	12602	-0.071	0.27	YES
24	CDK2	CDK2	CDK2	14035	-0.093	0.29	YES
25	PIK3R1	PIK3R1	PIK3R1	15186	-0.11	0.34	YES

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 ETHER LIPID METABOLISM.

Figure S52. 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 ARACHIDONIC ACID 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	PLA2G4E	PLA2G4E	PLA2G4E	68	0.85	0.067	YES
2	ALOX12B	ALOX12B	ALOX12B	92	0.81	0.13	YES
3	ALOX15B	ALOX15B	ALOX15B	107	0.78	0.2	YES
4	ALOX12	ALOX12	ALOX12	244	0.61	0.24	YES
5	PLA2G3	PLA2G3	PLA2G3	461	0.45	0.27	YES
6	GGT6	GGT6	GGT6	525	0.42	0.3	YES
7	PLA2G2F	PLA2G2F	PLA2G2F	620	0.38	0.32	YES
8	CBR3	CBR3	CBR3	664	0.36	0.35	YES
9	CYP2C19	CYP2C19	CYP2C19	710	0.35	0.38	YES
10	GPX3	GPX3	GPX3	1159	0.25	0.38	YES
11	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	1172	0.25	0.4	YES
12	CYP4A11	CYP4A11	CYP4A11	1347	0.22	0.41	YES
13	CYP4F3	CYP4F3	CYP4F3	1434	0.21	0.42	YES
14	AKR1C3	AKR1C3	AKR1C3	1870	0.16	0.42	YES
15	PTGS1	PTGS1	PTGS1	1967	0.16	0.43	YES
16	CYP4A22	CYP4A22	CYP4A22	2005	0.15	0.44	YES
17	CBR1	CBR1	CBR1	2246	0.14	0.44	YES
18	ALOX15	ALOX15	ALOX15	2589	0.11	0.43	NO
19	PTGES	PTGES	PTGES	2807	0.098	0.43	NO
20	CYP2C9	CYP2C9	CYP2C9	2866	0.095	0.44	NO
21	EPHX2	EPHX2	EPHX2	3202	0.079	0.43	NO
22	LTA4H	LTA4H	LTA4H	3230	0.078	0.43	NO
23	PLA2G4A	PLA2G4A	PLA2G4A	3341	0.074	0.44	NO
24	CYP2E1	CYP2E1	CYP2E1	4268	0.045	0.4	NO
25	PTGDS	PTGDS	PTGDS	4365	0.042	0.4	NO
26	GPX4	GPX4	GPX4	6842	-0.0024	0.29	NO
27	GPX1	GPX1	GPX1	7099	-0.0055	0.28	NO
28	PTGS2	PTGS2	PTGS2	7164	-0.0064	0.28	NO
29	LTC4S	LTC4S	LTC4S	8141	-0.018	0.23	NO
30	PLA2G12A	PLA2G12A	PLA2G12A	10428	-0.045	0.14	NO
31	CYP4F2	CYP4F2	CYP4F2	11696	-0.059	0.087	NO
32	PLA2G2D	PLA2G2D	PLA2G2D	12563	-0.071	0.055	NO
33	PLA2G6	PLA2G6	PLA2G6	12732	-0.073	0.054	NO
34	PTGES2	PTGES2	PTGES2	13507	-0.085	0.027	NO
35	GPX2	GPX2	GPX2	13646	-0.087	0.028	NO
36	GPX7	GPX7	GPX7	13734	-0.089	0.031	NO
37	HPGDS	HPGDS	HPGDS	15021	-0.11	-0.016	NO
38	CYP2C8	CYP2C8	CYP2C8	16623	-0.14	-0.074	NO
39	PLA2G2C	PLA2G2C	PLA2G2C	16641	-0.15	-0.063	NO
40	PLA2G5	PLA2G5	PLA2G5	17254	-0.16	-0.077	NO
41	GGT7	GGT7	GGT7	18348	-0.19	-0.11	NO
42	PTGIS	PTGIS	PTGIS	18886	-0.21	-0.12	NO
43	GGT5	GGT5	GGT5	19026	-0.22	-0.1	NO
44	GGT1	GGT1	GGT1	19947	-0.25	-0.12	NO
45	ALOX5	ALOX5	ALOX5	20941	-0.3	-0.14	NO
46	TBXAS1	TBXAS1	TBXAS1	21217	-0.32	-0.13	NO
47	PLA2G12B	PLA2G12B	PLA2G12B	21241	-0.32	-0.1	NO
48	CYP2U1	CYP2U1	CYP2U1	21638	-0.35	-0.091	NO
49	PLA2G2A	PLA2G2A	PLA2G2A	21814	-0.37	-0.068	NO
50	PLA2G1B	PLA2G1B	PLA2G1B	22213	-0.43	-0.051	NO
51	CYP2B6	CYP2B6	CYP2B6	22462	-0.47	-0.023	NO
52	PLA2G10	PLA2G10	PLA2G10	22513	-0.49	0.015	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 ARACHIDONIC ACID METABOLISM.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ARACHIDONIC 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 RETINOL METABOLISM

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	POLR3G	POLR3G	POLR3G	1518	0.2	0.057	YES
2	POLR2J2	POLR2J2	POLR2J2	1595	0.19	0.17	YES
3	POLR2J3	POLR2J3	POLR2J3	2399	0.12	0.21	YES
4	POLR2L	POLR2L	POLR2L	3622	0.065	0.2	YES
5	POLR3B	POLR3B	POLR3B	3768	0.06	0.23	YES
6	POLR2E	POLR2E	POLR2E	4929	0.029	0.2	YES
7	POLR1D	POLR1D	POLR1D	5197	0.024	0.2	YES
8	POLR2A	POLR2A	POLR2A	5370	0.021	0.2	YES
9	POLR2F	POLR2F	POLR2F	5471	0.019	0.21	YES
10	POLR2G	POLR2G	POLR2G	6347	0.005	0.18	YES
11	POLR3H	POLR3H	POLR3H	6536	0.002	0.17	YES
12	POLR2I	POLR2I	POLR2I	7898	-0.016	0.12	YES
13	POLR2J	POLR2J	POLR2J	8244	-0.02	0.12	YES
14	POLR1A	POLR1A	POLR1A	8853	-0.027	0.1	YES
15	POLR1E	POLR1E	POLR1E	8992	-0.028	0.12	YES
16	POLR3D	POLR3D	POLR3D	9258	-0.031	0.12	YES
17	POLR1C	POLR1C	POLR1C	10593	-0.046	0.093	YES
18	POLR3C	POLR3C	POLR3C	10698	-0.048	0.12	YES
19	POLR2K	POLR2K	POLR2K	10830	-0.049	0.14	YES
20	POLR2C	POLR2C	POLR2C	10964	-0.051	0.17	YES
21	POLR3A	POLR3A	POLR3A	10997	-0.051	0.2	YES
22	POLR2B	POLR2B	POLR2B	11197	-0.053	0.22	YES
23	POLR1B	POLR1B	POLR1B	11264	-0.054	0.25	YES
24	POLR3K	POLR3K	POLR3K	11378	-0.055	0.28	YES
25	POLR2D	POLR2D	POLR2D	12659	-0.072	0.27	YES
26	POLR3F	POLR3F	POLR3F	12830	-0.075	0.31	YES
27	ZNRD1	ZNRD1	ZNRD1	13014	-0.077	0.34	YES
28	POLR3GL	POLR3GL	POLR3GL	16433	-0.14	0.28	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 RETINOL METABOLISM.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RETINOL 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 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	MAPK10	MAPK10	MAPK10	1141	0.25	-0.008	YES
2	MAP3K6	MAP3K6	MAP3K6	1300	0.23	0.023	YES
3	MAP3K9	MAP3K9	MAP3K9	1333	0.23	0.06	YES
4	TGFB1	TGFB1	TGFB1	1630	0.19	0.078	YES
5	HRAS	HRAS	HRAS	1986	0.15	0.088	YES
6	CEBPA	CEBPA	CEBPA	2022	0.15	0.11	YES
7	MKNK2	MKNK2	MKNK2	2090	0.15	0.13	YES
8	MAPK6	MAPK6	MAPK6	2102	0.14	0.16	YES
9	RPS6KB2	RPS6KB2	RPS6KB2	2511	0.12	0.16	YES
10	MAP2K4	MAP2K4	MAP2K4	2784	0.1	0.16	YES
11	MAPK13	MAPK13	MAPK13	2920	0.093	0.17	YES
12	NFKBIA	NFKBIA	NFKBIA	3032	0.087	0.18	YES
13	MAPK11	MAPK11	MAPK11	3097	0.084	0.19	YES
14	MYC	MYC	MYC	3445	0.07	0.19	YES
15	TRADD	TRADD	TRADD	3489	0.069	0.2	YES
16	FOS	FOS	FOS	3632	0.064	0.2	YES
17	MAPK7	MAPK7	MAPK7	3796	0.059	0.2	YES
18	MAP3K4	MAP3K4	MAP3K4	3953	0.054	0.21	YES
19	MAPKAPK3	MAPKAPK3	MAPKAPK3	4145	0.048	0.21	YES
20	MAP2K1	MAP2K1	MAP2K1	4221	0.046	0.21	YES
21	MAP4K4	MAP4K4	MAP4K4	4412	0.041	0.21	YES
22	RAC1	RAC1	RAC1	4433	0.041	0.22	YES
23	RPS6KA5	RPS6KA5	RPS6KA5	4685	0.035	0.21	YES
24	MAP3K8	MAP3K8	MAP3K8	4744	0.034	0.21	YES
25	RPS6KA4	RPS6KA4	RPS6KA4	4772	0.033	0.22	YES
26	JUN	JUN	JUN	4811	0.032	0.22	YES
27	MKNK1	MKNK1	MKNK1	4881	0.03	0.22	YES
28	MAP2K2	MAP2K2	MAP2K2	4906	0.03	0.23	YES
29	MAP3K1	MAP3K1	MAP3K1	5089	0.026	0.22	YES
30	MAP4K5	MAP4K5	MAP4K5	5099	0.026	0.23	YES
31	MAPK3	MAPK3	MAPK3	5113	0.026	0.23	YES
32	SHC1	SHC1	SHC1	5171	0.024	0.23	YES
33	BRAF	BRAF	BRAF	5195	0.024	0.24	YES
34	MEF2A	MEF2A	MEF2A	5209	0.024	0.24	YES
35	RAF1	RAF1	RAF1	5303	0.022	0.24	NO
36	RPS6KB1	RPS6KB1	RPS6KB1	5842	0.013	0.22	NO
37	MAP3K5	MAP3K5	MAP3K5	5855	0.013	0.22	NO
38	MAP3K10	MAP3K10	MAP3K10	6202	0.007	0.2	NO
39	RELA	RELA	RELA	6223	0.0068	0.2	NO
40	MAPK14	MAPK14	MAPK14	6386	0.0045	0.2	NO
41	MAPK1	MAPK1	MAPK1	6427	0.0038	0.2	NO
42	RIPK1	RIPK1	RIPK1	6993	-0.0042	0.17	NO
43	MAX	MAX	MAX	7091	-0.0054	0.17	NO
44	NFKB1	NFKB1	NFKB1	7626	-0.012	0.15	NO
45	IKBKB	IKBKB	IKBKB	7634	-0.012	0.15	NO
46	MAP2K7	MAP2K7	MAP2K7	7653	-0.013	0.15	NO
47	MAP2K5	MAP2K5	MAP2K5	7830	-0.015	0.15	NO
48	MAPK12	MAPK12	MAPK12	8016	-0.017	0.14	NO
49	STAT1	STAT1	STAT1	8266	-0.02	0.13	NO
50	MAP3K7	MAP3K7	MAP3K7	8295	-0.02	0.14	NO
51	MAPKAPK2	MAPKAPK2	MAPKAPK2	8310	-0.02	0.14	NO
52	PAK1	PAK1	PAK1	8314	-0.02	0.14	NO
53	MAP4K2	MAP4K2	MAP4K2	8696	-0.025	0.13	NO
54	PAK2	PAK2	PAK2	9029	-0.029	0.12	NO
55	DAXX	DAXX	DAXX	9088	-0.029	0.12	NO
56	MAP2K3	MAP2K3	MAP2K3	9112	-0.03	0.12	NO
57	GRB2	GRB2	GRB2	9230	-0.031	0.12	NO
58	TGFB3	TGFB3	TGFB3	9283	-0.032	0.13	NO
59	MAP3K11	MAP3K11	MAP3K11	9326	-0.032	0.13	NO
60	SP1	SP1	SP1	9867	-0.038	0.11	NO
61	MAP3K13	MAP3K13	MAP3K13	10598	-0.047	0.09	NO
62	MAP3K3	MAP3K3	MAP3K3	10804	-0.049	0.089	NO
63	CHUK	CHUK	CHUK	11510	-0.057	0.068	NO
64	TGFBR1	TGFBR1	TGFBR1	11548	-0.057	0.076	NO
65	MEF2D	MEF2D	MEF2D	12049	-0.064	0.064	NO
66	CREB1	CREB1	CREB1	12081	-0.064	0.073	NO
67	MAPK4	MAPK4	MAPK4	12529	-0.07	0.065	NO
68	ARAF	ARAF	ARAF	12588	-0.071	0.075	NO
69	MAP3K2	MAP3K2	MAP3K2	12666	-0.072	0.083	NO
70	MAPKAPK5	MAPKAPK5	MAPKAPK5	12777	-0.074	0.091	NO
71	RPS6KA3	RPS6KA3	RPS6KA3	13288	-0.082	0.082	NO
72	MAPK8	MAPK8	MAPK8	13389	-0.083	0.091	NO
73	RPS6KA1	RPS6KA1	RPS6KA1	13637	-0.087	0.095	NO
74	MAPK9	MAPK9	MAPK9	13916	-0.091	0.098	NO
75	ELK1	ELK1	ELK1	14642	-0.1	0.083	NO
76	MAP4K3	MAP4K3	MAP4K3	14951	-0.11	0.088	NO
77	TRAF2	TRAF2	TRAF2	15576	-0.12	0.08	NO
78	ATF2	ATF2	ATF2	15972	-0.13	0.084	NO
79	MAP4K1	MAP4K1	MAP4K1	16452	-0.14	0.087	NO
80	MAP3K12	MAP3K12	MAP3K12	16593	-0.14	0.1	NO
81	MAP3K14	MAP3K14	MAP3K14	17251	-0.16	0.1	NO
82	RAPGEF2	RAPGEF2	RAPGEF2	17293	-0.16	0.13	NO
83	TGFB2	TGFB2	TGFB2	17999	-0.18	0.13	NO
84	RPS6KA2	RPS6KA2	RPS6KA2	19078	-0.22	0.12	NO
85	MAP2K6	MAP2K6	MAP2K6	20866	-0.3	0.087	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	ATP6V0A4	ATP6V0A4	ATP6V0A4	248	0.6	0.092	YES
2	ATP12A	ATP12A	ATP12A	314	0.55	0.18	YES
3	NDUFA4L2	NDUFA4L2	NDUFA4L2	521	0.42	0.24	YES
4	COX6B2	COX6B2	COX6B2	2248	0.13	0.19	NO
5	ATP6V1B1	ATP6V1B1	ATP6V1B1	2792	0.099	0.18	NO
6	ATP6V1D	ATP6V1D	ATP6V1D	2929	0.092	0.19	NO
7	ATP6V0C	ATP6V0C	ATP6V0C	3270	0.077	0.19	NO
8	ATP6V1F	ATP6V1F	ATP6V1F	3315	0.075	0.2	NO
9	NDUFS4	NDUFS4	NDUFS4	3693	0.062	0.2	NO
10	ATP6V0D1	ATP6V0D1	ATP6V0D1	3831	0.058	0.2	NO
11	ATP5H	ATP5H	ATP5H	4019	0.052	0.2	NO
12	ATP5D	ATP5D	ATP5D	4273	0.045	0.2	NO
13	ATP6V1E1	ATP6V1E1	ATP6V1E1	4310	0.044	0.2	NO
14	NDUFS8	NDUFS8	NDUFS8	4406	0.041	0.2	NO
15	NDUFS5	NDUFS5	NDUFS5	4442	0.04	0.21	NO
16	NDUFB4	NDUFB4	NDUFB4	4457	0.04	0.22	NO
17	NDUFS7	NDUFS7	NDUFS7	4672	0.035	0.21	NO
18	ATP5A1	ATP5A1	ATP5A1	4787	0.032	0.21	NO
19	NDUFA11	NDUFA11	NDUFA11	4856	0.031	0.22	NO
20	ATP6V1H	ATP6V1H	ATP6V1H	4942	0.029	0.22	NO
21	ATP6V0E1	ATP6V0E1	ATP6V0E1	4960	0.029	0.22	NO
22	ATP6V1B2	ATP6V1B2	ATP6V1B2	4969	0.029	0.23	NO
23	NDUFB10	NDUFB10	NDUFB10	5109	0.026	0.22	NO
24	ATP6V1A	ATP6V1A	ATP6V1A	5180	0.024	0.22	NO
25	NDUFB7	NDUFB7	NDUFB7	5353	0.021	0.22	NO
26	ATP5J	ATP5J	ATP5J	5441	0.02	0.22	NO
27	SDHC	SDHC	SDHC	5547	0.018	0.22	NO
28	COX8A	COX8A	COX8A	5576	0.017	0.22	NO
29	NDUFB9	NDUFB9	NDUFB9	5594	0.017	0.22	NO
30	NDUFC1	NDUFC1	NDUFC1	5657	0.016	0.22	NO
31	ATP6V0A1	ATP6V0A1	ATP6V0A1	5716	0.015	0.22	NO
32	UQCRC2	UQCRC2	UQCRC2	5723	0.015	0.22	NO
33	UQCR10	UQCR10	UQCR10	5726	0.015	0.23	NO
34	ATP5I	ATP5I	ATP5I	5759	0.014	0.23	NO
35	NDUFV3	NDUFV3	NDUFV3	5766	0.014	0.23	NO
36	UQCR11	UQCR11	UQCR11	5804	0.014	0.23	NO
37	ATP6V1G1	ATP6V1G1	ATP6V1G1	5942	0.011	0.23	NO
38	NDUFS6	NDUFS6	NDUFS6	5977	0.011	0.23	NO
39	NDUFB1	NDUFB1	NDUFB1	6078	0.0091	0.22	NO
40	COX6B1	COX6B1	COX6B1	6159	0.0078	0.22	NO
41	LHPP	LHPP	LHPP	6160	0.0077	0.22	NO
42	COX7B	COX7B	COX7B	6164	0.0076	0.22	NO
43	UQCRQ	UQCRQ	UQCRQ	6167	0.0075	0.23	NO
44	COX4I1	COX4I1	COX4I1	6370	0.0047	0.22	NO
45	ATP4A	ATP4A	ATP4A	6387	0.0044	0.22	NO
46	NDUFA6	NDUFA6	NDUFA6	6418	0.004	0.22	NO
47	NDUFB3	NDUFB3	NDUFB3	6428	0.0038	0.22	NO
48	NDUFV2	NDUFV2	NDUFV2	6469	0.0031	0.22	NO
49	COX10	COX10	COX10	6583	0.0013	0.21	NO
50	NDUFV1	NDUFV1	NDUFV1	6585	0.0013	0.21	NO
51	ATP5C1	ATP5C1	ATP5C1	6611	0.00091	0.21	NO
52	NDUFAB1	NDUFAB1	NDUFAB1	6690	-0.00034	0.21	NO
53	NDUFB5	NDUFB5	NDUFB5	6705	-0.00058	0.21	NO
54	COX5A	COX5A	COX5A	6727	-0.00088	0.21	NO
55	COX6A1	COX6A1	COX6A1	6733	-0.001	0.21	NO
56	ATP5B	ATP5B	ATP5B	6783	-0.0017	0.2	NO
57	CYC1	CYC1	CYC1	6822	-0.0022	0.2	NO
58	UQCRC1	UQCRC1	UQCRC1	6827	-0.0023	0.2	NO
59	NDUFB8	NDUFB8	NDUFB8	6923	-0.0033	0.2	NO
60	UQCRFS1	UQCRFS1	UQCRFS1	7018	-0.0044	0.2	NO
61	COX7C	COX7C	COX7C	7025	-0.0046	0.2	NO
62	ATP5G3	ATP5G3	ATP5G3	7147	-0.0062	0.19	NO
63	ATP5G2	ATP5G2	ATP5G2	7235	-0.0072	0.19	NO
64	ATP5F1	ATP5F1	ATP5F1	7302	-0.0082	0.19	NO
65	COX7A2	COX7A2	COX7A2	7414	-0.0096	0.18	NO
66	COX5B	COX5B	COX5B	7491	-0.011	0.18	NO
67	UQCRHL	UQCRHL	UQCRHL	7498	-0.011	0.18	NO
68	ATP5L	ATP5L	ATP5L	7670	-0.013	0.18	NO
69	NDUFB6	NDUFB6	NDUFB6	7680	-0.013	0.18	NO
70	UQCRH	UQCRH	UQCRH	7688	-0.013	0.18	NO
71	COX6C	COX6C	COX6C	7690	-0.013	0.19	NO
72	ATP6V1E2	ATP6V1E2	ATP6V1E2	7737	-0.014	0.19	NO
73	PPA2	PPA2	PPA2	7841	-0.015	0.18	NO
74	NDUFA9	NDUFA9	NDUFA9	8026	-0.017	0.18	NO
75	NDUFA2	NDUFA2	NDUFA2	8136	-0.018	0.18	NO
76	ATP6V0B	ATP6V0B	ATP6V0B	8172	-0.019	0.18	NO
77	NDUFA1	NDUFA1	NDUFA1	8213	-0.019	0.18	NO
78	ATP5E	ATP5E	ATP5E	8556	-0.023	0.17	NO
79	ATP5G1	ATP5G1	ATP5G1	8594	-0.024	0.17	NO
80	NDUFA7	NDUFA7	NDUFA7	8642	-0.024	0.17	NO
81	NDUFA10	NDUFA10	NDUFA10	8714	-0.025	0.18	NO
82	NDUFB2	NDUFB2	NDUFB2	8761	-0.026	0.18	NO
83	NDUFS3	NDUFS3	NDUFS3	8771	-0.026	0.18	NO
84	PPA1	PPA1	PPA1	9229	-0.031	0.17	NO
85	NDUFS2	NDUFS2	NDUFS2	9261	-0.031	0.17	NO
86	SDHB	SDHB	SDHB	9348	-0.032	0.17	NO
87	UQCRB	UQCRB	UQCRB	9385	-0.033	0.18	NO
88	NDUFA3	NDUFA3	NDUFA3	9415	-0.033	0.18	NO
89	ATP6AP1	ATP6AP1	ATP6AP1	9443	-0.034	0.18	NO
90	SDHD	SDHD	SDHD	9779	-0.037	0.18	NO
91	COX17	COX17	COX17	9872	-0.038	0.18	NO
92	NDUFA8	NDUFA8	NDUFA8	10414	-0.045	0.16	NO
93	NDUFA4	NDUFA4	NDUFA4	10682	-0.047	0.16	NO
94	COX15	COX15	COX15	11198	-0.053	0.15	NO
95	COX7A2L	COX7A2L	COX7A2L	11489	-0.057	0.14	NO
96	SDHA	SDHA	SDHA	11612	-0.058	0.15	NO
97	ATP6V1C2	ATP6V1C2	ATP6V1C2	12007	-0.063	0.14	NO
98	NDUFS1	NDUFS1	NDUFS1	12723	-0.073	0.12	NO
99	ATP6V1C1	ATP6V1C1	ATP6V1C1	12797	-0.074	0.13	NO
100	COX8C	COX8C	COX8C	12866	-0.075	0.14	NO
101	TCIRG1	TCIRG1	TCIRG1	12926	-0.076	0.15	NO
102	COX7B2	COX7B2	COX7B2	12973	-0.076	0.16	NO
103	COX11	COX11	COX11	14141	-0.095	0.13	NO
104	NDUFA5	NDUFA5	NDUFA5	14236	-0.096	0.14	NO
105	ATP6V0A2	ATP6V0A2	ATP6V0A2	14904	-0.11	0.13	NO
106	COX6A2	COX6A2	COX6A2	16928	-0.15	0.064	NO
107	COX7A1	COX7A1	COX7A1	17021	-0.16	0.087	NO
108	COX4I2	COX4I2	COX4I2	17174	-0.16	0.11	NO
109	ATP6V0D2	ATP6V0D2	ATP6V0D2	17374	-0.16	0.13	NO
110	ATP6V0E2	ATP6V0E2	ATP6V0E2	18399	-0.2	0.11	NO
111	ATP4B	ATP4B	ATP4B	19127	-0.22	0.12	NO
112	ATP6V1G2	ATP6V1G2	ATP6V1G2	20136	-0.26	0.12	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 = ESCA-TP.mRNAseq_RPKM_log2.txt
Phenotype data file = ESCA-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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